1 00:00:05,799 --> 00:00:08,702 WELCOME EVERYONE TO THE 2024 2 00:00:08,702 --> 00:00:10,504 WORKSHOP ON RESEARCH IN THE 3 00:00:10,504 --> 00:00:11,071 TREATMENT OF MITRAL VALVE 4 00:00:11,071 --> 00:00:11,338 PROLAPSE. 5 00:00:11,338 --> 00:00:14,274 THE WORKSHOP IS SPONSORED BY THE 6 00:00:14,274 --> 00:00:16,776 NATIONAL NATIONAL HEART, LUNG 7 00:00:16,776 --> 00:00:17,644 AND BLOOD INSTITUTE OF THE 8 00:00:17,644 --> 00:00:18,745 U.S. NATIONAL INSTITUTES OF 9 00:00:18,745 --> 00:00:19,045 HEALTH. 10 00:00:19,045 --> 00:00:21,181 THE GOAL OF THE WORKSHOP IS TO 11 00:00:21,181 --> 00:00:23,283 REVIEW THE STATE OF THE SCIENCE 12 00:00:23,283 --> 00:00:25,051 AND IDENTIFY RESEARCH NEEDS AND 13 00:00:25,051 --> 00:00:26,286 OPPORTUNITIES FOR THE TREATMENT 14 00:00:26,286 --> 00:00:29,189 OF INDIVIDUALS WITH MITRAL VALVE 15 00:00:29,189 --> 00:00:31,358 PROLAPSE INCLUDING THOSE AT RISK 16 00:00:31,358 --> 00:00:33,593 FOR SUDDEN CARDIAC ARREST OR 17 00:00:33,593 --> 00:00:35,695 SUDDEN CARDIAC DEATH. 18 00:00:35,695 --> 00:00:38,865 IT'S NOT NECESSARY THE 19 00:00:38,865 --> 00:00:39,799 PARTICIPANTS ACHIEVE CONSENSUS. 20 00:00:39,799 --> 00:00:41,735 INDIVIDUAL PARTICIPANTS COULD 21 00:00:41,735 --> 00:00:42,602 IDENTIFY DIFFERENT RESEARCH 22 00:00:42,602 --> 00:00:43,570 NEEDS AND OPPORTUNITIES AND 23 00:00:43,570 --> 00:00:46,506 THAT'S FINE. 24 00:00:46,506 --> 00:00:49,809 THIS 2024 WORKSHOP IS AN UPDATE 25 00:00:49,809 --> 00:00:53,213 OF OUR 2021 WORKSHOP AND PART OF 26 00:00:53,213 --> 00:00:55,115 THE NHLBI'S IMPLEMENTATION OF 27 00:00:55,115 --> 00:00:57,017 THE CARDIOVASCULAR ADVANCES IN 28 00:00:57,017 --> 00:01:01,021 RESEARCH AND OPPORTUNITIES 29 00:01:01,021 --> 00:01:02,289 LEGACY OR CAROL ACT. 30 00:01:02,289 --> 00:01:05,926 THE WORKSHOP IS BEING CARRIED ON 31 00:01:05,926 --> 00:01:06,359 TWO PLATFORMS. 32 00:01:06,359 --> 00:01:10,864 ZOOM AND NIH VIDEOCAST. 33 00:01:10,864 --> 00:01:12,799 ON ZOOM WE HAVE TWO OVERLAPPING 34 00:01:12,799 --> 00:01:14,367 GROUPS OF PARTICIPANTS. 35 00:01:14,367 --> 00:01:16,870 WE HAVE THOSE WHO PARTICIPATED 36 00:01:16,870 --> 00:01:19,573 IN THE 2021 WORKSHOP, THANK YOU 37 00:01:19,573 --> 00:01:21,041 FOR RETURNING. 38 00:01:21,041 --> 00:01:30,617 AND WE HAVE PARTICIPANTS WHOSE 39 00:01:30,617 --> 00:01:32,252 RESEARCH IS FUNDED IN PART BY 40 00:01:32,252 --> 00:01:35,889 THE CAROL ACT AND TWO ADDITIONAL 41 00:01:35,889 --> 00:01:38,024 PARTICIPANTS. 42 00:01:38,024 --> 00:01:39,759 THE ZOOM PLATFORM ALSO HAS NHLBI 43 00:01:39,759 --> 00:01:44,564 STAFF AND THE SUPPORT STAFF. 44 00:01:44,564 --> 00:01:45,131 EVERYONE ELSE IS ON NIH 45 00:01:45,131 --> 00:01:49,302 VIDEOCAST. 46 00:01:49,302 --> 00:01:51,004 EACH PRESENTATION IS SCHEDULED 47 00:01:51,004 --> 00:01:51,705 FOR 20 MINUTES. 48 00:01:51,705 --> 00:01:53,940 THERE MAY BE TIME FOR DISCUSSION 49 00:01:53,940 --> 00:01:56,910 AND QUESTIONS WITHIN THAT 20 50 00:01:56,910 --> 00:01:57,143 MINUTES. 51 00:01:57,143 --> 00:01:58,011 BUT THERE ARE ALSO DISCUSSION 52 00:01:58,011 --> 00:01:59,579 PERIODS AT THE END OF EACH 53 00:01:59,579 --> 00:02:02,816 SESSION. 54 00:02:02,816 --> 00:02:05,151 THOSE ON ZOOM CAN ASK QUESTIONS 55 00:02:05,151 --> 00:02:07,587 THROUGH THE Q&A FEATURE OF ZOOM. 56 00:02:07,587 --> 00:02:09,789 THOSE ON VIDEOCAST AS YOU HEARD 57 00:02:09,789 --> 00:02:11,558 A MOMENT AGO CAN SUBMIT 58 00:02:11,558 --> 00:02:13,827 QUESTIONS THROUGH THE LIVE 59 00:02:13,827 --> 00:02:15,028 FEEDBACK LINK. 60 00:02:15,028 --> 00:02:20,166 THE LIVE FEEDBACK PRODUCES AN 61 00:02:20,166 --> 00:02:23,403 E-MAIL IN A WORKSHOP SPECIFIC 62 00:02:23,403 --> 00:02:23,637 MAILBOX. 63 00:02:23,637 --> 00:02:27,574 WE'LL TRY TO MONITOR THAT 64 00:02:27,574 --> 00:02:33,580 MAILBOX DURING THE WORKSHOP. 65 00:02:33,580 --> 00:02:35,215 OKAY. 66 00:02:35,215 --> 00:02:40,020 WE HAVE HAD A COUPLE LATE DROP 67 00:02:40,020 --> 00:02:41,588 OUTS IN THE AGENDA. 68 00:02:41,588 --> 00:02:43,757 WE HAD HOPED TO HAVE CONGRESSMAN 69 00:02:43,757 --> 00:02:46,192 ANDY BARR, WHO IS THE ORIGINAL 70 00:02:46,192 --> 00:02:48,795 SPONSOR OF THE CAROL ACT WHICH 71 00:02:48,795 --> 00:02:51,898 IS IN FACT NAMED AFTER HIS WIFE 72 00:02:51,898 --> 00:02:56,670 CAROL WHOSE DEATH WAS ATTRIBUTED 73 00:02:56,670 --> 00:02:58,538 TO MITRAL VALVE PROLAPSE. 74 00:02:58,538 --> 00:03:00,106 UNFORTUNATELY CONGRESSMAN BARR 75 00:03:00,106 --> 00:03:01,741 CAN'T BE WITH US TODAY SO I 76 00:03:01,741 --> 00:03:03,777 BELIEVE WE HAVE ALL OF THE 77 00:03:03,777 --> 00:03:14,321 SPEAKERS FOR THE FIRST SESSION. 78 00:03:15,021 --> 00:03:17,824 MY SUGGESTION IS WE'LL PROCEED 79 00:03:17,824 --> 00:03:21,227 AND ADJUST THE AGENDA THROUGH 80 00:03:21,227 --> 00:03:23,763 THE DAY AS NECESSARY. 81 00:03:23,763 --> 00:03:27,567 DOES ANYONE HAVE THOUGHTS ON 82 00:03:27,567 --> 00:03:37,877 THAT OR COMMENTS? 83 00:03:46,186 --> 00:03:47,721 HEARING NONE -- YES. 84 00:03:47,721 --> 00:03:51,725 >> SOUNDS GOOD. 85 00:03:51,725 --> 00:03:53,159 >> LET'S DO THAT THEN. 86 00:03:53,159 --> 00:03:55,562 I SEE NO REASON TO WAIT ANY 87 00:03:55,562 --> 00:03:56,896 LONGER LET'S BEGIN WITH THE 88 00:03:56,896 --> 00:03:59,265 FIRST SESSION ON IMAGING AND THE 89 00:03:59,265 --> 00:04:03,403 FIRST SPEAKER IS JUDY HUNG FROM 90 00:04:03,403 --> 00:04:04,738 MASSACHUSETTS GENERAL HOSPITAL. 91 00:04:04,738 --> 00:04:14,848 JUDY. 92 00:04:26,726 --> 00:04:37,203 TO FIND THE TREATMENT GAPS FOR 93 00:04:37,971 --> 00:04:39,072 MITRAL VALVE PROLAPSE -- 94 00:04:39,072 --> 00:04:43,810 >> JUDY, WE HAVE A PROBLEM WITH 95 00:04:43,810 --> 00:04:44,177 YOUR SOUND. 96 00:04:44,177 --> 00:04:47,213 I DON'T KNOW IF YOU CAN DO 97 00:04:47,213 --> 00:04:49,082 SOMETHING WITH YOUR MICROPHONE 98 00:04:49,082 --> 00:04:51,284 BECAUSE OTHERWISE WE CAN'T HEAR 99 00:04:51,284 --> 00:04:52,719 YOU OR I CAN'T HEAR YOU. 100 00:04:52,719 --> 00:04:56,856 >> WE DID THE SOUND CHECK 101 00:04:56,856 --> 00:04:58,958 EVERYTHING LOOKED FINE SO LET ME 102 00:04:58,958 --> 00:04:59,559 SEE -- 103 00:04:59,559 --> 00:05:00,460 >> SOUNDS BETTER NOW. 104 00:05:00,460 --> 00:05:01,895 IT'S CLEARER NOW. 105 00:05:01,895 --> 00:05:05,732 >> OKAY. 106 00:05:05,732 --> 00:05:07,867 WELL, THAT WAS GREAT WHOEVER 107 00:05:07,867 --> 00:05:08,802 DISCLOSED THAT. 108 00:05:08,802 --> 00:05:11,371 ANYWAY, LET ME KNOW IF I SOUND 109 00:05:11,371 --> 00:05:11,638 METALLIC. 110 00:05:11,638 --> 00:05:16,009 GOD FORBID I WANT TO SOUND MORE 111 00:05:16,009 --> 00:05:18,678 LIKE AN A.I. AVATAR. 112 00:05:18,678 --> 00:05:20,980 I HAVE NO FINANCIAL DISCLOSURES 113 00:05:20,980 --> 00:05:26,853 BUT DIRECT THE PRIMARY CLINICAL 114 00:05:26,853 --> 00:05:36,963 TRIAL. 115 00:05:38,364 --> 00:05:38,898 EC 116 00:05:38,898 --> 00:05:41,334 ECHOCARDIO GRAPHY IS AN IMAGE OF 117 00:05:41,334 --> 00:05:43,570 THE HEART AND COMPARES TO OTHER 118 00:05:43,570 --> 00:05:46,272 MODALITIES. 119 00:05:46,272 --> 00:05:50,810 IT'S ALSO NONINVASIVE, SAFE 120 00:05:50,810 --> 00:05:52,846 IMAGING MODALITY AND AVAILABLE 121 00:05:52,846 --> 00:05:54,948 AND ACCESSIBLE AND RELATIVELY 122 00:05:54,948 --> 00:06:02,655 COST EFFECTIVE. 123 00:06:02,655 --> 00:06:09,996 ECHOCARDIOGRAPHY IS THE PRIMARY 124 00:06:09,996 --> 00:06:13,132 INITIAL IMAGING MODALITY TO 125 00:06:13,132 --> 00:06:13,733 DIAGNOSE MITRAL VALVE MITRAL 126 00:06:13,733 --> 00:06:15,468 VALVE AND HAS A HIGH ACCURACY 127 00:06:15,468 --> 00:06:18,838 RATE WITH A LARGE NUMBER OF 128 00:06:18,838 --> 00:06:23,576 STUDIES CONFIRMING ACCURACY OF 129 00:06:23,576 --> 00:06:24,277 DIAGNOSIS COMPARED TO SURGICAL 130 00:06:24,277 --> 00:06:28,548 INSPECTION. 131 00:06:28,548 --> 00:06:32,886 AND ECHO HAS HAD AN IMPORTANT 132 00:06:32,886 --> 00:06:37,223 ROLE IN THE ACCURATE DIAGNOSIS 133 00:06:37,223 --> 00:06:37,924 OF MITRAL VALVE PROLAPSE BASED 134 00:06:37,924 --> 00:06:42,095 ON INSIGHTS FROM 3-D CARD YOKING 135 00:06:42,095 --> 00:06:44,697 GRAPHY WHICH HELPED US REFINE 136 00:06:44,697 --> 00:06:46,232 THE DIAGNOSIS OF MVP MAKING IT 137 00:06:46,232 --> 00:06:47,467 MORE ACCURATE. 138 00:06:47,467 --> 00:06:50,036 THE PREVALENCE OF MVP WAS FOUND 139 00:06:50,036 --> 00:06:54,908 TO BE LOWER ON THAT PREVIOUSLY 140 00:06:54,908 --> 00:07:01,714 THOUGHT IN AN NIH/NHLBI 141 00:07:01,714 --> 00:07:03,149 FRAMINGHAM HEART STUDY. 142 00:07:03,149 --> 00:07:05,652 PRIOR TO THE STUDY PUBLISHED IN 143 00:07:05,652 --> 00:07:09,055 1999, THE PREVALENCE OF MVP WAS 144 00:07:09,055 --> 00:07:10,189 THOUGHT TO BE ANYWHERE FROM 5% 145 00:07:10,189 --> 00:07:11,090 TO 15%. 146 00:07:11,090 --> 00:07:14,027 WHEN THEY APPLIED THE MORE 147 00:07:14,027 --> 00:07:19,566 ACCURATE DIAGNOSIS OF MVP IT WAS 148 00:07:19,566 --> 00:07:23,670 FOUND MORE A 2.4% PREVALENCE 149 00:07:23,670 --> 00:07:28,241 WHICH IS A SIGNIFICANT CHANGE IN 150 00:07:28,241 --> 00:07:31,678 OUR AWARENESS OF MVP. 151 00:07:31,678 --> 00:07:33,813 SO MITRAL VALVE PROLAPSE IS 152 00:07:33,813 --> 00:07:39,619 ESSENTIALLY DEFINED BY 153 00:07:39,619 --> 00:07:40,219 ECHOCARDIOGRAPHIC CRITERIA. 154 00:07:40,219 --> 00:07:45,325 ON THE LEFT IS NORMAL MITRAL 155 00:07:45,325 --> 00:07:50,263 VALVE WITH THE IMAGE AND THE 156 00:07:50,263 --> 00:07:53,066 NORMAL MITRAL VALVE CLOSURE IS 157 00:07:53,066 --> 00:07:58,037 AT THE PLANE RIGHT HERE AND 158 00:07:58,037 --> 00:08:00,640 SHOULDN'T HAVE LEAFLETS INTO THE 159 00:08:00,640 --> 00:08:01,908 LEFT ATRIUM. 160 00:08:01,908 --> 00:08:03,209 THAT'S THE ISSUE WITH MITRAL 161 00:08:03,209 --> 00:08:04,711 VALVE PROLAPSE AS YOU SEE ON THE 162 00:08:04,711 --> 00:08:09,115 SCREEN ON THE RIGHT IT'S WHEN 163 00:08:09,115 --> 00:08:13,386 THE LEAFLET EXTENDS TWO MILL 164 00:08:13,386 --> 00:08:15,622 MITERS INTO THE LEFT ATRIUM AND 165 00:08:15,622 --> 00:08:18,625 SEE A NICE EXAMPLE HERE. 166 00:08:18,625 --> 00:08:22,562 THE POSTERIOR LEAFLET BUCKLING 167 00:08:22,562 --> 00:08:27,634 BELOW THE PLANE WITH THE 168 00:08:27,634 --> 00:08:29,736 DIAGNOSIS OF MITRAL VALVE 169 00:08:29,736 --> 00:08:30,370 PROLAPSE. 170 00:08:30,370 --> 00:08:34,007 ALSO IMPORTANT TO DISTINGUISH 171 00:08:34,007 --> 00:08:36,876 BETWEEN PROLAPSE AND MITRAL 172 00:08:36,876 --> 00:08:39,545 VALVE FLARE AND THIS IS WHEN YOU 173 00:08:39,545 --> 00:08:43,583 HAVE THE TIP OF THE LEAFLET INTO 174 00:08:43,583 --> 00:08:45,385 THE ATRIUM AND TYPICALLY DUE TO 175 00:08:45,385 --> 00:08:51,391 THE FACT OF A RUPTURED CORD AND 176 00:08:51,391 --> 00:08:55,561 THE TIP IS FULLY INTO THE LEFT 177 00:08:55,561 --> 00:08:58,965 ATRIAL CHAMBER. 178 00:08:58,965 --> 00:09:01,234 AND THE IMPORTANT ISSUE WITH 179 00:09:01,234 --> 00:09:03,236 RECOGNIZING FLAIL IS ONCE YOU 180 00:09:03,236 --> 00:09:05,905 HAVE FLAIL, IT'S OFTEN ALMOST 181 00:09:05,905 --> 00:09:07,407 ALWAYS ASSOCIATED WITH 182 00:09:07,407 --> 00:09:14,080 SIGNIFICANT OR SEVERE MITRAL 183 00:09:14,080 --> 00:09:15,615 REGURGITATION. 184 00:09:15,615 --> 00:09:17,750 AND UNDERSTANDING THE MITRAL 185 00:09:17,750 --> 00:09:21,754 CORDAL ANATOMY IS KEY CAN TO 186 00:09:21,754 --> 00:09:23,690 UNDERSTANDING WHY PROLAPSE 187 00:09:23,690 --> 00:09:25,291 DEVELOPS TO FLAIL LEAFLET AND 188 00:09:25,291 --> 00:09:30,563 THE CORDS OF THE MITRAL VALVE 189 00:09:30,563 --> 00:09:32,765 ONE ARE THE BASAL CORD FOUR TO 190 00:09:32,765 --> 00:09:34,901 EIGHT IN EACH LEAFLET PROVIDING 191 00:09:34,901 --> 00:09:39,138 THE BASIC STRUCTURAL SUPPORT. 192 00:09:39,138 --> 00:09:40,773 HOWEVER, THE WORKHORSE CORDS ARE 193 00:09:40,773 --> 00:09:43,009 THE PRIMARY CORDI AND ATTACH 194 00:09:43,009 --> 00:09:46,212 ALONG THE TIPS OF THE LEAFLETS 195 00:09:46,212 --> 00:09:50,550 AND RESPONSIBLE FOR COLLAPSING 196 00:09:50,550 --> 00:09:52,952 OF THE LEAFLETS. 197 00:09:52,952 --> 00:09:55,455 AND IN THE SCHEMATIC YOU SEE THE 198 00:09:55,455 --> 00:09:57,356 PROGRESSION OF WHAT HAPPENS IN 199 00:09:57,356 --> 00:09:59,225 THE NORMAL VALVE SITUATION TO 200 00:09:59,225 --> 00:10:07,166 DEVELOP INTO PROLAPSE AND THEN 201 00:10:07,166 --> 00:10:11,204 DEVELOP INTO FLAIL AND YOU HAVE 202 00:10:11,204 --> 00:10:13,139 PNEUM OF NIGHT CORDS INTACT AND 203 00:10:13,139 --> 00:10:18,678 HOLDING THE LEAFLETS TOGETHER. 204 00:10:18,678 --> 00:10:21,514 IN THE PROLAPSE YOU HAVE THE 205 00:10:21,514 --> 00:10:27,086 LEAFLET BODY EXTENDS INTO THE 206 00:10:27,086 --> 00:10:31,557 LEFT ATRIAL BODY BUT STILL HAVE 207 00:10:31,557 --> 00:10:33,493 SOME ELEMENT OF IS CHORDAL 208 00:10:33,493 --> 00:10:35,561 RUPTURE AND AT THAT POINT WHAT 209 00:10:35,561 --> 00:10:43,569 HAPPENS IS LEAFLETS YOU HAVE A 210 00:10:43,569 --> 00:10:48,975 FLAIL PORTION OF LEAFLET. 211 00:10:48,975 --> 00:10:59,519 SO THERE'S AN ANATOMIC SPECTRUM 212 00:11:04,724 --> 00:11:05,825 FIBRAL ELASTICITY AND INCREASING 213 00:11:05,825 --> 00:11:08,194 THE MORE ADVANCED FORMS OF 214 00:11:08,194 --> 00:11:12,298 PROLAPSE WITH THE MOST SEVERE 215 00:11:12,298 --> 00:11:18,037 FORM CALLED BARLOW'S DISEASE 216 00:11:18,037 --> 00:11:20,706 NAMED AF THE CARDIOLOGIST WHO 217 00:11:20,706 --> 00:11:24,677 FIRST DESCRIBED CLINICALLY AND 218 00:11:24,677 --> 00:11:25,578 BY PHYSICAL DIAGNOSIS THE SIGNS 219 00:11:25,578 --> 00:11:31,284 OF MITRAL VALVE PROLAPSE AND 220 00:11:31,284 --> 00:11:31,984 LEAFLET. 221 00:11:31,984 --> 00:11:42,528 SO FIBROELASTIC DEFICIENCY FIRST 222 00:11:46,833 --> 00:11:51,003 DESCRIBED BY ALAIN CARPENTIER 223 00:11:51,003 --> 00:11:54,040 AND YOU'LL HAVE RUPTURED CORDS 224 00:11:54,040 --> 00:11:56,876 AND LEAFLET REDUNDANCY AND 225 00:11:56,876 --> 00:12:07,420 THICKENING ON HIS TOLL -- HIS 226 00:12:08,688 --> 00:12:09,455 HISTOLOGY ASSOCIATED WITH MITRAL 227 00:12:09,455 --> 00:12:10,323 VALVE PROLAPSE. 228 00:12:10,323 --> 00:12:13,025 THESE ARE THE CLINICAL FEATURES 229 00:12:13,025 --> 00:12:17,730 YOU SEE IN FIBROELASTIC 230 00:12:17,730 --> 00:12:18,364 DEFICIENCY. 231 00:12:18,364 --> 00:12:23,236 THE PATIENTS ARE OLDER THAN 60 232 00:12:23,236 --> 00:12:24,670 AND SHORT HISTORY OF VALVE 233 00:12:24,670 --> 00:12:29,041 DISEASE AND ASSOCIATED WITH 234 00:12:29,041 --> 00:12:30,376 FIBRAL INEFFICIENCY AND HAVE 235 00:12:30,376 --> 00:12:32,645 THICKENING ASSOCIATED AND OFTEN 236 00:12:32,645 --> 00:12:35,047 ISOLATED TO A SINGLE SEGMENT AND 237 00:12:35,047 --> 00:12:40,553 OFTEN THE P2 SEGMENT. 238 00:12:40,553 --> 00:12:43,256 CHORDALE ARE OFTEN THIN WITH 239 00:12:43,256 --> 00:12:46,259 RUPTURE AND HAVE A SMALL SIZE 240 00:12:46,259 --> 00:12:47,560 AND THERE ARE ABSENT CAL 241 00:12:47,560 --> 00:12:54,967 FICTIONS. 242 00:12:54,967 --> 00:13:00,072 LET'S TALK ABOUT OPPOSITE END 243 00:13:00,072 --> 00:13:03,576 TERMED BARLOW'S DISEASE. 244 00:13:03,576 --> 00:13:06,445 IT AFFECTS PATIENTS AT A YOUNGER 245 00:13:06,445 --> 00:13:06,779 AGE. 246 00:13:06,779 --> 00:13:09,181 THEY PRESENT LESS THAN 60 YEARS. 247 00:13:09,181 --> 00:13:11,884 THERE'S OFTEN A LONG HISTORY OF 248 00:13:11,884 --> 00:13:15,922 CARDIAC MURMURS AND CARDIAC 249 00:13:15,922 --> 00:13:21,227 VALVE DISEASE PRESENT EARLY IN 250 00:13:21,227 --> 00:13:25,698 AGE AND IT'S A VERY DIFFUSE 251 00:13:25,698 --> 00:13:27,400 COMPLEX LESIONS WITH 252 00:13:27,400 --> 00:13:31,170 MULTI-SEGMENT OR EVEN ENTIRE 253 00:13:31,170 --> 00:13:32,972 VALVE INVOLVEMENT, LOSS OF 254 00:13:32,972 --> 00:13:37,910 EXCESS TISSUE WITH THICK 255 00:13:37,910 --> 00:13:38,811 REDUNDANT LEAFLETS AND 256 00:13:38,811 --> 00:13:40,513 DEGENERATION OF THE LEAFLETS. 257 00:13:40,513 --> 00:13:47,620 YOU HAVE OFTEN ELONGATED 258 00:13:47,620 --> 00:13:51,590 THICKENED AND THEY EVENTUALLY 259 00:13:51,590 --> 00:14:02,134 RUPTURE AND LARGE SIZES AND AND 260 00:14:03,602 --> 00:14:08,374 CALCIFICATION IS OFTEN PRESENT. 261 00:14:08,374 --> 00:14:12,878 AND I WANT TO POINT OUT THERE 262 00:14:12,878 --> 00:14:17,917 ARE A LOT OF TERMS USED FOR 263 00:14:17,917 --> 00:14:28,461 PROLAPSE MOMENT PEOPLE REFER TO 264 00:14:37,069 --> 00:14:37,303 B 265 00:14:37,303 --> 00:14:38,971 BARLOW'S AND THERE'S BILLOWING 266 00:14:38,971 --> 00:14:43,609 LEAFLETS AND FLOPPY VALVE 267 00:14:43,609 --> 00:14:46,746 SYNDROME BECAUSE IT LOOKS LIKE 268 00:14:46,746 --> 00:14:55,554 AUTO FLOPPY EARS AND JOHN BARLOW 269 00:14:55,554 --> 00:14:57,790 WHO CONTINUED TO THE TERM OF 270 00:14:57,790 --> 00:15:00,026 SEVERE PROLAPSE. 271 00:15:00,026 --> 00:15:01,127 THERE'S IN BETWEEN VARIANTS. 272 00:15:01,127 --> 00:15:02,695 YOU CAN HAVE ADVANCE NOT JUST 273 00:15:02,695 --> 00:15:05,731 ONE SEGMENT INVOLVEMENT BUT 274 00:15:05,731 --> 00:15:07,600 MULTIPLE SEGMENTS INVOLVED AS 275 00:15:07,600 --> 00:15:09,301 SHOWN HERE. 276 00:15:09,301 --> 00:15:13,305 THERE'S THE P2 SEGMENT EXTENDS 277 00:15:13,305 --> 00:15:17,843 TO THE P2 SEGMENT AND YOU CAN 278 00:15:17,843 --> 00:15:19,612 SEE IT CAN HAVE FURTHER 279 00:15:19,612 --> 00:15:29,188 ADVANCEMENT. 280 00:15:29,188 --> 00:15:34,260 HERE YOU HAVE A FORM OF BARLOW'S 281 00:15:34,260 --> 00:15:36,128 WHERE PRACTICALLY EVERY LEAFLET 282 00:15:36,128 --> 00:15:39,598 IS ABNORMAL AND YOU CAN SEE THE 283 00:15:39,598 --> 00:15:43,502 WHOLE POSTERIOR LEAFLET IS 284 00:15:43,502 --> 00:15:50,142 PROLAPSED WITH A1 AND A3 ONE -- 285 00:15:50,142 --> 00:15:54,547 WITH ONE SEGMENT LOOKING NORMAL 286 00:15:54,547 --> 00:15:59,752 BEFORE YOU CALL OUT A BARLOW'S 287 00:15:59,752 --> 00:15:59,985 SITE. 288 00:15:59,985 --> 00:16:03,522 FROM FIBROELASTIC DEFICIENCY YOU 289 00:16:03,522 --> 00:16:05,624 SEE THE SPECTRUM OF MITRAL VALVE 290 00:16:05,624 --> 00:16:07,593 PROLAPSE WE SEE BUT THERE ARE 291 00:16:07,593 --> 00:16:11,597 ALSO PRODROMAL FORMS DESCRIBED 292 00:16:11,597 --> 00:16:20,539 AS WELL. 293 00:16:20,539 --> 00:16:24,510 THIS IS FROM WORK FROM THE MORPH 294 00:16:24,510 --> 00:16:27,146 OLO 295 00:16:27,146 --> 00:16:32,885 MORPHOLOGIES ARE NON-DIAGNOSTIC 296 00:16:32,885 --> 00:16:34,453 BUT HAVE FEATURES CONSISTENT 297 00:16:34,453 --> 00:16:36,255 WITH THE PROLAPSE AND OFTEN 298 00:16:36,255 --> 00:16:41,994 CALLED THE PROTOMAL OR MINIMAL 299 00:16:41,994 --> 00:16:44,797 SYSTOLIC DISPLACEMENT AND YOU'LL 300 00:16:44,797 --> 00:16:54,006 HAVE EXCESS LEAFLET MOTION, AND 301 00:16:54,006 --> 00:16:55,574 NOT QUITE MEETING THE CRITERIA 302 00:16:55,574 --> 00:16:56,542 FOR PROLAPSE. 303 00:16:56,542 --> 00:17:01,280 AND OFTEN YOU'LL GET THE ASEM TI 304 00:17:01,280 --> 00:17:04,049 OF COAPTATION BETWEEN THE 305 00:17:04,049 --> 00:17:07,853 POSTERIOR AND ANTERIOR LEAFLET 306 00:17:07,853 --> 00:17:12,758 IN THE PRODOMAL FORM AS WELL. 307 00:17:12,758 --> 00:17:14,326 IT'S NON DIAGNOSTIC BUT SHARES 308 00:17:14,326 --> 00:17:21,100 FEATURES CHARACTERISTIC OF MVP. 309 00:17:21,100 --> 00:17:23,903 ANOTHER IMPORTANT IMAGING 310 00:17:23,903 --> 00:17:26,372 FEATURE OF MITRAL VALVE PROLAPSE 311 00:17:26,372 --> 00:17:36,849 THAT ECHOCARDIOGRAPHY SHOW 312 00:17:39,652 --> 00:17:49,128 ESSENTIALLY INDENTATIONS THAT 313 00:17:49,128 --> 00:17:54,633 OCCUR IN THE INDENTATION BETWEEN 314 00:17:54,633 --> 00:17:58,170 P2 AND P1 AND P3 AND THEY GET 315 00:17:58,170 --> 00:18:03,709 EXAGGERATED AND IT'S A MECHANISM 316 00:18:03,709 --> 00:18:13,152 FOR MIGHT RAL 3 -- MITRAL 317 00:18:13,152 --> 00:18:13,485 REGURGITATION. 318 00:18:13,485 --> 00:18:15,454 YOU CAN SEE WHAT HAPPENS HERE. 319 00:18:15,454 --> 00:18:19,592 THESE ARE BEEN DEFINED AS 320 00:18:19,592 --> 00:18:22,661 INDENTATIONS WHICH ARE GREATER 321 00:18:22,661 --> 00:18:24,997 OR EQUAL TO 50% OF THE LEAFLET. 322 00:18:24,997 --> 00:18:26,966 DEATH HAS TO BE AT LEAST 50% AND 323 00:18:26,966 --> 00:18:32,338 ERROR SHOWS IN INDENTATION AND 324 00:18:32,338 --> 00:18:36,542 IT'S IMPORTANT TO RECOGNIZE 325 00:18:36,542 --> 00:18:38,911 BECAUSE THE CAUSE OF MR THAT IS 326 00:18:38,911 --> 00:18:40,980 NOT DIRECTLY RELATED TO THE 327 00:18:40,980 --> 00:18:42,248 FLAIL MECHANISM AND HAS 328 00:18:42,248 --> 00:18:43,449 IMPLICATIONS FOR PLANNING FOR 329 00:18:43,449 --> 00:18:47,486 TYPE OF REPAIR, SURGICAL VERSUS 330 00:18:47,486 --> 00:18:50,356 TIER, FOR IF THERE'S SIGNIFICANT 331 00:18:50,356 --> 00:18:53,192 PORTION OF THE MR THAT GOES 332 00:18:53,192 --> 00:18:55,361 THROUGH A CLEFT THEN TIER IS 333 00:18:55,361 --> 00:18:58,163 LESS LIKELY TO BE SUCCESSFULLY 334 00:18:58,163 --> 00:19:06,472 DONE. 335 00:19:06,472 --> 00:19:10,175 ANOTHER IMPORTANT ANATOMIC 336 00:19:10,175 --> 00:19:16,849 FEATURE IS MITRAL ANULAR 337 00:19:16,849 --> 00:19:22,821 DYSFUNCTION DISPLACEMENT OF THE 338 00:19:22,821 --> 00:19:31,597 HINGE POINT BETWEEN THE ANULUS 339 00:19:31,597 --> 00:19:39,505 AND LOOKS AT THE LEAVE LET 340 00:19:39,505 --> 00:19:41,740 PROLAPSE AND THE CLINICAL 341 00:19:41,740 --> 00:19:42,841 ASSOCIATION WE'RE INCREASINGLY 342 00:19:42,841 --> 00:19:43,542 RECOGNIZING IS ASSOCIATED WITH 343 00:19:43,542 --> 00:19:53,585 SUDDEN TEJ. 344 00:19:53,585 --> 00:20:01,493 THIS IS A SPECIMEN OF MITRAL 345 00:20:01,493 --> 00:20:02,761 ANNULAR DISJUNCTION. 346 00:20:02,761 --> 00:20:06,699 THIS IS VERY DISCREET AND 347 00:20:06,699 --> 00:20:10,169 ATTACHES THE ATRIAL PORTION TO 348 00:20:10,169 --> 00:20:10,736 THE VENTRICULAR PORTION. 349 00:20:10,736 --> 00:20:13,005 THIS IS ON THE RIGHT WHAT YOU 350 00:20:13,005 --> 00:20:22,648 SEE WITH MITRAL ANNULAR 351 00:20:22,648 --> 00:20:28,187 DISJUNCTION AND SEE WHERE THE 352 00:20:28,187 --> 00:20:34,093 ATRIAL ANNULUS STARTS. 353 00:20:34,093 --> 00:20:35,961 YOU HAVE THIS LONG FIBROUS 354 00:20:35,961 --> 00:20:39,765 TISSUE THAT SEPARATES THE TWO 355 00:20:39,765 --> 00:20:45,437 SPACES. 356 00:20:45,437 --> 00:20:50,042 AND WHAT'S IMPORTANT ABOUT THE 357 00:20:50,042 --> 00:20:54,246 MITRAL ANNULUS SYNDROME IT'S 358 00:20:54,246 --> 00:20:58,851 FELT BECAUSE THE ABNORMAL SPACE 359 00:20:58,851 --> 00:21:02,855 BETWEEN ANNULUS AND VENTRICLE 360 00:21:02,855 --> 00:21:07,593 CAN RESULT IN ABNORMAL 361 00:21:07,593 --> 00:21:09,294 MECHANICAL FORCES ON THE VALVE 362 00:21:09,294 --> 00:21:10,896 AND MUSCLE WHICH CAN LEAD TO AN 363 00:21:10,896 --> 00:21:14,333 ARRHYTHMIC SYNDROME. 364 00:21:14,333 --> 00:21:18,370 THIS IS THE PAPER BY A GROUP 365 00:21:18,370 --> 00:21:19,371 WHICH DEMONSTRATED AN 366 00:21:19,371 --> 00:21:22,908 ASSOCIATION OF MITRAL ANNULAR 367 00:21:22,908 --> 00:21:27,846 DISJUNCTION WITH VENTRICULAR A 368 00:21:27,846 --> 00:21:34,853 RARIDGE -- ARRHYTHMIA AND SUDDN 369 00:21:34,853 --> 00:21:35,487 DEATH. 370 00:21:35,487 --> 00:21:40,092 AND LOOKING AT ECHO FEATURES OF 371 00:21:40,092 --> 00:21:41,827 ARRHYTHMIC MITRAL VALVE 372 00:21:41,827 --> 00:21:45,097 PROLAPSE, THIS GROUP DEFINED THE 373 00:21:45,097 --> 00:21:48,200 PRESENCE OF MITRAL ANNULAR 374 00:21:48,200 --> 00:21:52,638 DYSFUNCTION AND LEAFLETS AS 375 00:21:52,638 --> 00:21:54,239 INDEPENDENT RISK FACTORS FOR 376 00:21:54,239 --> 00:22:00,846 ARRHYTHMIAS IN THIS POPULATION. 377 00:22:00,846 --> 00:22:05,083 AND THIS PATTERN BY ECHO 378 00:22:05,083 --> 00:22:07,252 DESCRIBED AS A DOUBLE PEAK 379 00:22:07,252 --> 00:22:10,589 STRAIN PATTERN IS POTENTIALLY A 380 00:22:10,589 --> 00:22:12,991 MECHANISTIC MARKER THAT FOR 381 00:22:12,991 --> 00:22:14,793 THESE ABNORMAL MECHANICS AND 382 00:22:14,793 --> 00:22:18,397 FIBROSIS THAT OCCURS IN THE 383 00:22:18,397 --> 00:22:23,602 SETTING OF MITRAL ANNULAR 384 00:22:23,602 --> 00:22:27,606 DYSFUNCTION AND THIS DESCRIBES 385 00:22:27,606 --> 00:22:34,880 THE MECHANICS THAT RELATE TO 386 00:22:34,880 --> 00:22:37,516 MITO CARDIAL FIBROSIS IN 387 00:22:37,516 --> 00:22:38,083 PATIENTS WITH MITRAL VALVE 388 00:22:38,083 --> 00:22:41,887 PROLAPSE. 389 00:22:41,887 --> 00:22:45,924 AND THIS IS FROM THE PAPER AND 390 00:22:45,924 --> 00:22:51,964 WHAT YOU SEE ON THE TOP IS SORT 391 00:22:51,964 --> 00:22:55,601 OF THE PRODOMAL FORM OF THE 392 00:22:55,601 --> 00:22:57,002 SYSTOLIC PROLAPSE AND YOU HAVE 393 00:22:57,002 --> 00:22:59,137 TIS PLACEMENT BUT NOT PROLAPSE 394 00:22:59,137 --> 00:23:02,474 YET AND GET A SINGLE PEAK. 395 00:23:02,474 --> 00:23:05,811 IN PATIENTS WITH MITRAL ANNULAR 396 00:23:05,811 --> 00:23:08,547 DYSFUNCTION AND THE VENTRICULAR 397 00:23:08,547 --> 00:23:09,348 MECHANICS BECAUSE OF THE EXTRA 398 00:23:09,348 --> 00:23:14,553 TUG THAT HAPPENS YOU GET A 399 00:23:14,553 --> 00:23:17,956 DOUBLE PEAK FORMED AS SHOWN HERE 400 00:23:17,956 --> 00:23:23,695 THE SPECTRAL PATTERN BY ECHO. 401 00:23:23,695 --> 00:23:27,165 AND IT'S THOUGHT THESE ABNORMAL 402 00:23:27,165 --> 00:23:30,102 MECHANICS ARE ACTUALLY MARKERS 403 00:23:30,102 --> 00:23:32,905 FOR FIBROSIS AND THIS SHOWS THE 404 00:23:32,905 --> 00:23:38,110 DOUBLE PEAK PATTERN IS 405 00:23:38,110 --> 00:23:43,615 ASSOCIATED AS BY MRI IS 406 00:23:43,615 --> 00:23:46,485 ASSOCIATED WITH INCREASING OF 407 00:23:46,485 --> 00:23:50,355 VENTRICULAR ARRHYTHMIA EVENTS. 408 00:23:50,355 --> 00:23:51,657 THERE'S A NICE MECHANISTIC BASIS 409 00:23:51,657 --> 00:23:54,626 FOR WHY THAT HAPPENS WITH A 410 00:23:54,626 --> 00:23:57,095 DOUBLE PEAK IN THE ABNORMAL 411 00:23:57,095 --> 00:23:58,196 MECHANICAL STRESS ON THE PATHWAY 412 00:23:58,196 --> 00:24:03,302 MUSCLE. 413 00:24:03,302 --> 00:24:06,605 AND OF COURSE ECHOCARDIOGRAPHY 414 00:24:06,605 --> 00:24:11,543 IS THE MAINSTAY FOR HOW WE 415 00:24:11,543 --> 00:24:15,414 ASSESS HOW MUCH MITRAL 416 00:24:15,414 --> 00:24:20,819 REGIRTHTARE GUGIR GUGIR 417 00:24:20,819 --> 00:24:24,923 REGURGITATION IS ASSOCIATED IN 418 00:24:24,923 --> 00:24:25,557 THE MITRAL VALVE PROLAPSE SHOWN 419 00:24:25,557 --> 00:24:35,634 HERE. 420 00:24:35,634 --> 00:24:40,405 AND THE AMERICAN SOCIETY OF 421 00:24:40,405 --> 00:24:46,945 ECHOCA 422 00:24:46,945 --> 00:24:47,579 ECHOCA 423 00:24:47,579 --> 00:24:48,180 ECHOCARDIOGRAPHY HAS A BASE 424 00:24:48,180 --> 00:24:49,848 INCLUDING ANATOMIC FEATURES OF 425 00:24:49,848 --> 00:24:52,751 PRESENCE OF A FLAIL LEAFLET FOR 426 00:24:52,751 --> 00:24:56,388 INSTANCE AND ENLARGED LV AND 427 00:24:56,388 --> 00:25:02,561 COLOR DOPPLER CRITERIA BY ECHO 428 00:25:02,561 --> 00:25:10,869 IN GOING ABOUT GRADING MITRAL 429 00:25:10,869 --> 00:25:13,238 REGURGITATION AND WHETHER MILD, 430 00:25:13,238 --> 00:25:14,673 MODERATE OR SEVERE AND MR 431 00:25:14,673 --> 00:25:22,848 QUANTIFICATION. 432 00:25:22,848 --> 00:25:27,586 TO SUMMARIZE, ECHO HE'S A ROLE 433 00:25:27,586 --> 00:25:29,521 IN MITRAL VALVE PROLAPSE. 434 00:25:29,521 --> 00:25:31,189 IT'S THE BASIS FOR DIAGNOSIS OF 435 00:25:31,189 --> 00:25:35,594 MVP AND THE SUB A TOPIC SUB 436 00:25:35,594 --> 00:25:37,729 TYPES. 437 00:25:37,729 --> 00:25:40,298 THE FUNCTIONAL FEATURES ARE FELT 438 00:25:40,298 --> 00:25:43,602 TO BE AT HIGH RISK FOR ADVERSE 439 00:25:43,602 --> 00:25:49,341 EVENTS AN PERFORMED BY 440 00:25:49,341 --> 00:25:52,210 ECHOCARDIOGRAPHY AND PROVIDES 441 00:25:52,210 --> 00:25:57,783 THE ANATOMIC AND FUNCTION DATA 442 00:25:57,783 --> 00:25:59,317 TO TAILOR THERAPY FOR PATIENTS. 443 00:25:59,317 --> 00:26:03,755 THANK YOU VERY MUCH. 444 00:26:03,755 --> 00:26:05,357 >> THANK YOU VERY MUCH, JUDY. 445 00:26:05,357 --> 00:26:10,796 THAT WAS A VERY COMPREHENSIVE 446 00:26:10,796 --> 00:26:11,196 DISCUSSION. 447 00:26:11,196 --> 00:26:12,431 DOES ANYONE HAVE ANY BRIEF 448 00:26:12,431 --> 00:26:20,038 QUESTIONS OR COMMENTS? 449 00:26:20,038 --> 00:26:27,212 >> JUDY, IT'S DAVID ADAMS, HOW 450 00:26:27,212 --> 00:26:27,813 ARE YOU? 451 00:26:27,813 --> 00:26:29,081 >> GREAT, HOW ARE YOU? 452 00:26:29,081 --> 00:26:31,583 >> I WANTED TO PLANT THE SEED 453 00:26:31,583 --> 00:26:35,487 AND ONE TOPIC I LOOKED FORWARD 454 00:26:35,487 --> 00:26:37,989 TO SPEAKING TO YOU ABOUT THE 455 00:26:37,989 --> 00:26:39,758 FRONT END WHICH YOU TALK ABOUT 456 00:26:39,758 --> 00:26:43,595 THE ANATOMY AND HOW THAT MIGHT 457 00:26:43,595 --> 00:26:47,599 HELP US CHOOSE A POTENTIAL 458 00:26:47,599 --> 00:26:50,001 OPTION INCLUDING MEDICAL 459 00:26:50,001 --> 00:26:51,269 MANAGEMENT AND TIER IN TERMS OF 460 00:26:51,269 --> 00:26:55,173 DEGREE BUT WHAT I HOPE WE CAN 461 00:26:55,173 --> 00:26:56,742 TALK ABOUT A LITTLE WHILE LONGER 462 00:26:56,742 --> 00:27:00,178 IS ABOUT THE POST REPAIR 463 00:27:00,178 --> 00:27:00,479 ASSESSMENT. 464 00:27:00,479 --> 00:27:01,947 I THINK THIS IS SOMETHING THAT 465 00:27:01,947 --> 00:27:03,582 ALL OF US WANT TO GET MORE 466 00:27:03,582 --> 00:27:05,350 EDUCATED ABOUT AS WE MOVE INTO 467 00:27:05,350 --> 00:27:08,086 THIS AREA BOTH WITH SURGERY AND 468 00:27:08,086 --> 00:27:12,324 WITH PARTICULARLY WITH TIER 469 00:27:12,324 --> 00:27:14,025 BECAUSE I DON'T THINK IT'S 470 00:27:14,025 --> 00:27:17,896 REALLY WELL DEFINED OUTSIDE 471 00:27:17,896 --> 00:27:19,564 EXACTLY HOW ALL THE OUTCOMES GET 472 00:27:19,564 --> 00:27:23,602 GRADED AND HOPING WE CAN LEAVE 473 00:27:23,602 --> 00:27:27,105 THIS AS AN ACTION ITEM FROM THE 474 00:27:27,105 --> 00:27:28,406 MEETING HOW WILL WE ASSESS 475 00:27:28,406 --> 00:27:31,610 POST-REPAIR OUTCOMES IN 476 00:27:31,610 --> 00:27:41,787 PATIENTS. 477 00:27:47,025 --> 00:27:48,927 >> WE'RE LEARNING HOW TO 478 00:27:48,927 --> 00:27:50,428 QUANTITATE AND AS WE 479 00:27:50,428 --> 00:27:51,630 INCREASINGLY RECOGNIZE THE 480 00:27:51,630 --> 00:27:55,000 IMAGING MARKERS FOR HIGH RISK 481 00:27:55,000 --> 00:27:58,236 SUCH AS SUDDEN DEATH I THINK 482 00:27:58,236 --> 00:28:00,172 THEY CAN BE LOOKED AT POST 483 00:28:00,172 --> 00:28:01,439 SURGERY OR POST INTERVENTION TO 484 00:28:01,439 --> 00:28:02,808 SEE IF THEY IMPROVE. 485 00:28:02,808 --> 00:28:10,015 I KNOW PART OF ONE OF THE 486 00:28:10,015 --> 00:28:14,386 RESEARCH GRANTS FUNDED BY THE 487 00:28:14,386 --> 00:28:15,854 CAROL ACT IS ONE OF THE 488 00:28:15,854 --> 00:28:16,588 FEATURES. 489 00:28:16,588 --> 00:28:19,624 >> WE'VE BEEN INVOLVED IN THE 490 00:28:19,624 --> 00:28:22,427 TRANS-CATHETER TRIALS AND DEPEND 491 00:28:22,427 --> 00:28:24,996 ON THE CRISP AN CLEAR DATA AND 492 00:28:24,996 --> 00:28:27,566 THEN MOVE TO CLINICS AND IT'S 493 00:28:27,566 --> 00:28:28,600 NOT SO CLEAR WHAT IS SUCCESS 494 00:28:28,600 --> 00:28:28,834 ANYMORE. 495 00:28:28,834 --> 00:28:31,903 I THINK WE HAVE AN OPPORTUNITY 496 00:28:31,903 --> 00:28:33,805 OR I CERTAINLY THINK IT'S AN 497 00:28:33,805 --> 00:28:38,376 ACTIVE AREA FOR RESEARCH IS HOW 498 00:28:38,376 --> 00:28:40,679 ARE WE GOING TO ASSESS OUTCOMES 499 00:28:40,679 --> 00:28:42,414 NOT JUST IDENTIFY PATIENTS AND 500 00:28:42,414 --> 00:28:44,716 TREATMENT BUT ALSO ASSESS 501 00:28:44,716 --> 00:28:46,885 OUTCOMES INCLUDING HOW DO WE 502 00:28:46,885 --> 00:28:52,157 CREATE SOME WAY TO DO MORE THAN 503 00:28:52,157 --> 00:28:54,326 JUST IMMEDIATE POST PROCEDURE TD 504 00:28:54,326 --> 00:28:54,626 ASSESSMENT. 505 00:28:54,626 --> 00:28:55,594 WE HAVE TO THINK ABOUT THAT AS A 506 00:28:55,594 --> 00:29:05,704 GROUP. 507 00:29:06,538 --> 00:29:14,346 YOU NEED TO LOOK AT POST REPAIR 508 00:29:14,346 --> 00:29:17,816 INTERVENTION AND MAY BE AN AREA 509 00:29:17,816 --> 00:29:19,084 WHERE ARTIFICIAL INTELLIGENCE 510 00:29:19,084 --> 00:29:20,986 CAN HELP US BY DEVELOPING 511 00:29:20,986 --> 00:29:23,188 ALGORITHMS THAT ARE POTENTIALLY 512 00:29:23,188 --> 00:29:24,322 MORE PRODUCIBLE AND NOT JUST 513 00:29:24,322 --> 00:29:26,157 WITHIN CORE LAPSE AND I KNOW 514 00:29:26,157 --> 00:29:28,994 AGAIN ONE OF THE RESEARCH GRANTS 515 00:29:28,994 --> 00:29:31,730 IS LOOKING INTO RADIOMICS TO 516 00:29:31,730 --> 00:29:38,136 ASSESS THAT. 517 00:29:38,136 --> 00:29:39,137 >> I'LL LET THE FLOOR KEEP 518 00:29:39,137 --> 00:29:39,371 MOVING. 519 00:29:39,371 --> 00:29:44,676 THANK YOU. 520 00:29:44,676 --> 00:29:51,850 IS 521 00:29:51,850 --> 00:29:57,722 >> THE NEXT SPEAKER IS DIPAN 522 00:29:57,722 --> 00:30:01,860 SHAH FROM HOUSTON METHODIST. 523 00:30:01,860 --> 00:30:07,532 >> THANK YOU, FRANK AND THANKS 524 00:30:07,532 --> 00:30:12,270 TO THE NIH AND I THINK JUDY DID 525 00:30:12,270 --> 00:30:15,840 AN OUTSTANDING JOB OF SETTING UP 526 00:30:15,840 --> 00:30:18,043 THE BACKGROUND BEHIND MIGHT RAL 527 00:30:18,043 --> 00:30:20,045 VALVE PROLAPSE AND TALKING ABOUT 528 00:30:20,045 --> 00:30:26,785 THE VALUE OF ECHOCARDIOGRAPHY 529 00:30:26,785 --> 00:30:28,253 AND THE INITIAL ASSESSMENT WILL 530 00:30:28,253 --> 00:30:31,589 START WITH THAT AND SOMEWHERE 531 00:30:31,589 --> 00:30:35,260 THERE'S QUESTIONS STILL 532 00:30:35,260 --> 00:30:35,927 REMAINING AFTER ECHOCARDIOGRAPHY 533 00:30:35,927 --> 00:30:37,595 WHERE IT CAN BE USEFUL. 534 00:30:37,595 --> 00:30:40,265 ONE AREA IS IN ASSESSING THE 535 00:30:40,265 --> 00:30:40,932 SEVERITY OF REGURGITATION. 536 00:30:40,932 --> 00:30:43,301 I THINK MOST OF US IN OUR 537 00:30:43,301 --> 00:30:48,506 PRACTICE HAVE ADOPTED THAT IN 538 00:30:48,506 --> 00:30:54,446 CASES WHERE DISCREPANCY OF 539 00:30:54,446 --> 00:30:57,882 REGURGITATION CARDIAC MRI CAN BE 540 00:30:57,882 --> 00:31:00,151 USEFUL TO LOOK AT THE 541 00:31:00,151 --> 00:31:03,021 REMODELLING OF THE VENTRICLE AND 542 00:31:03,021 --> 00:31:05,690 REFLECTED IN THE ASE GUIDELINES 543 00:31:05,690 --> 00:31:08,727 IN 2017 WHICH HIGHLIGHTED THE 544 00:31:08,727 --> 00:31:10,528 ROLE FOR CARDIAC MRI. 545 00:31:10,528 --> 00:31:15,667 WITH THAT BACKDROP I'LL FOCUS IS 546 00:31:15,667 --> 00:31:19,471 HOW CARDIAC MRI IN THE 547 00:31:19,471 --> 00:31:23,441 ASSESSMENT OF THE ARRHYTHMIC 548 00:31:23,441 --> 00:31:24,943 PHENOTYPE. 549 00:31:24,943 --> 00:31:25,944 AND MITRAL VALVE PROLAPSE NOT 550 00:31:25,944 --> 00:31:27,312 UNCOMMON BY ANY MEANS. 551 00:31:27,312 --> 00:31:29,547 EITHER BY THE CURRENT DEFINITION 552 00:31:29,547 --> 00:31:31,116 WHICH ARE MORE IMPROVED COMPARED 553 00:31:31,116 --> 00:31:34,019 TO WHAT PEOPLE WERE USING IN THE 554 00:31:34,019 --> 00:31:38,056 '70s AND '80s AND PRESENT IN 2% 555 00:31:38,056 --> 00:31:43,661 TO 3% OF THE POPULATION AND 556 00:31:43,661 --> 00:31:47,599 THOUGHT TO BE BENIGN SOME CAN 557 00:31:47,599 --> 00:31:49,434 EXPERIENCE ARRHYTHMIAS AND 558 00:31:49,434 --> 00:31:49,868 CARDIAC DEATH. 559 00:31:49,868 --> 00:31:52,871 IF YOU LOOK AMOUNT THE LEFT SIDE 560 00:31:52,871 --> 00:31:55,607 THIS IS ONE ESTIMATE OF THE 561 00:31:55,607 --> 00:31:58,276 ANNUAL INCIDENTS OF SUDDEN 562 00:31:58,276 --> 00:32:01,246 CARDIAC DEATH IT IN THE GENERAL 563 00:32:01,246 --> 00:32:02,147 POPULATION HIGHER IN THE 564 00:32:02,147 --> 00:32:02,914 PATIENTS WITH MITRAL VALVE 565 00:32:02,914 --> 00:32:05,316 PROLAPSE BUT NOT AS HIGH AS 566 00:32:05,316 --> 00:32:12,223 REPORTED COHORTS OF OTHERS AND 567 00:32:12,223 --> 00:32:15,794 THE PARADOX OF NUMBERS IS THE 568 00:32:15,794 --> 00:32:18,630 PROLAPSE IS PRESENT OR 569 00:32:18,630 --> 00:32:22,300 PREVALENCE IS HIGHER THAN 570 00:32:22,300 --> 00:32:24,569 HYPERTROPIC CARDIOMYOPATHY AND 571 00:32:24,569 --> 00:32:27,272 THE EVENTS PLAY BE HIGHER THAN 572 00:32:27,272 --> 00:32:34,512 WHAT OCCURS FROM HYPERTROPIC 573 00:32:34,512 --> 00:32:36,614 CARDIOMYOPATHY AND THE ABSOLUTE 574 00:32:36,614 --> 00:32:39,184 NUMBER OF EVENTS. 575 00:32:39,184 --> 00:32:42,487 THOUGH THE OVER ALL INDENTS ARE 576 00:32:42,487 --> 00:32:43,855 LOW IN MITRAL VALVE PROLAPSE 577 00:32:43,855 --> 00:32:45,356 BECAUSE OF THE LARGE PREVALENCE 578 00:32:45,356 --> 00:32:46,224 OF PATIENTS IT'S AN IMPORTANT 579 00:32:46,224 --> 00:32:56,501 THING TO STUDY. 580 00:32:57,869 --> 00:32:59,604 THIS HIGHLIGHTS THE RISK AND WE 581 00:32:59,604 --> 00:33:02,273 NEED TO IDENTIFY THE SUB GROUP 582 00:33:02,273 --> 00:33:06,911 THAT INCREASED ARRHYTHMIC RISK. 583 00:33:06,911 --> 00:33:09,414 SO, THERE'S A NUMBER OF PROPOSED 584 00:33:09,414 --> 00:33:10,048 MARKERS OUT THERE. 585 00:33:10,048 --> 00:33:16,321 MANY OF THE PANELISTS REALLY 586 00:33:16,321 --> 00:33:17,455 RESPONSIBLE FOR CONTRIBUTING 587 00:33:17,455 --> 00:33:20,091 THIS LITERATURE. 588 00:33:20,091 --> 00:33:27,599 WE TALK ABOUT MONITORING AND 589 00:33:27,599 --> 00:33:31,603 PREMATURE VENTRICULAR ACTION AS 590 00:33:31,603 --> 00:33:34,606 A RISK FACTOR IN MITRAL VALVE 591 00:33:34,606 --> 00:33:38,243 PROLAPSE AND DYSFUNCTION OF 592 00:33:38,243 --> 00:33:41,379 STRAIN PATTERN AND THIS PATTERN 593 00:33:41,379 --> 00:33:43,515 STRIKED AS WELL. 594 00:33:43,515 --> 00:33:49,254 AND SO WHAT I'M GOING TO DO IS 595 00:33:49,254 --> 00:33:50,622 SEE HOW CARDIAC MR CAN HELP 596 00:33:50,622 --> 00:33:56,227 BUILD THE MARKERS AVAILABLE OR 597 00:33:56,227 --> 00:33:59,898 PROPOSED FROM ECHOCARDIOGRAPHY 598 00:33:59,898 --> 00:34:03,701 AND YOU LOOK AT THE MOTION IN 599 00:34:03,701 --> 00:34:07,739 PATIENTS WITH THOSE WITH THE 600 00:34:07,739 --> 00:34:11,576 ADVANTAGE OF MRI WE HAVE THIS 601 00:34:11,576 --> 00:34:14,145 HYPER DYNAMIC MOTION OF THE 602 00:34:14,145 --> 00:34:16,981 LATERAL AND BASAL WALL OFTEN 603 00:34:16,981 --> 00:34:20,285 FITTING OF THE MID LATERAL WALL 604 00:34:20,285 --> 00:34:22,620 WHERE THE MUSCLE INSERTS AND IF 605 00:34:22,620 --> 00:34:24,656 THE MOVIE WOULD CONTINUE IT 606 00:34:24,656 --> 00:34:26,758 WOULD SHOW YOU IN THE PATIENTS 607 00:34:26,758 --> 00:34:27,926 WITH MITRAL VALVE PROLAPSE OFTEN 608 00:34:27,926 --> 00:34:30,862 YOU CAN HAVE A PARADOXICAL 609 00:34:30,862 --> 00:34:34,032 MOTION OF THE MUSCLE WHERE ON 610 00:34:34,032 --> 00:34:37,602 THE LEFT SIDE IT SHOULD DESCEND 611 00:34:37,602 --> 00:34:43,841 TOWARD THE APEX TOWARDS THE 612 00:34:43,841 --> 00:34:46,244 PROLAPSE AND IN BARLOW'S 613 00:34:46,244 --> 00:34:48,279 PATIENTS YOU SEE THE MUSCLE 614 00:34:48,279 --> 00:34:50,348 MOVING PARADOXICALLY UPWARD 615 00:34:50,348 --> 00:34:52,750 THROUGH THE ANNULAR PLANE 616 00:34:52,750 --> 00:34:53,952 OPPOSED TO DOWN TOWARDS THE 617 00:34:53,952 --> 00:35:01,492 APEX. 618 00:35:01,492 --> 00:35:03,394 S 619 00:35:04,729 --> 00:35:08,566 I THINK THE ABILITY TO SEE THE 620 00:35:08,566 --> 00:35:09,901 MORPHOLOGY OF THE VENTRICLE AND 621 00:35:09,901 --> 00:35:12,337 VALVES AND THE DYNAMIC OF THE 622 00:35:12,337 --> 00:35:15,139 MOTION BY MRI CAN BE HELPFUL. 623 00:35:15,139 --> 00:35:18,176 ONE WAY IT'S ADDED INSIGHTS IS 624 00:35:18,176 --> 00:35:22,313 IN TRYING TO BETTER CHARACTERIZE 625 00:35:22,313 --> 00:35:26,484 MITRAL ANNULAR DYSFUNCTION AND 626 00:35:26,484 --> 00:35:31,589 TO SEPARATE WHAT'S TRUE 627 00:35:31,589 --> 00:35:35,026 DYSFUNCTION FROM PSEUDO MAB. 628 00:35:35,026 --> 00:35:37,495 THIS WAS BROUGHT UP IN THE 629 00:35:37,495 --> 00:35:40,231 JOURNAL OF THE AMERICAN SOCIETY 630 00:35:40,231 --> 00:35:46,037 OF ECHO YEARS AGO LOOK BEING AT 631 00:35:46,037 --> 00:35:47,472 A TRUE SEPARATION FOR 632 00:35:47,472 --> 00:35:49,407 DYSFUNCTION FROM THE BOTTOM 633 00:35:49,407 --> 00:35:52,443 RIGHT WHERE YOU SIMPLY ARE 634 00:35:52,443 --> 00:35:55,580 HAVING THE MITRAL LEAFLET WHICH 635 00:35:55,580 --> 00:35:57,849 IS HUGGING UP AGAINST THE LEFT 636 00:35:57,849 --> 00:35:59,917 WALL AND CAN BE HARD TO SEPARATE 637 00:35:59,917 --> 00:36:03,488 THE ATRIAL WALL FROM THE LEAFLET 638 00:36:03,488 --> 00:36:05,456 HUGGING NEXT IT THE WALL AND 639 00:36:05,456 --> 00:36:08,326 MAKE SURE YOU'RE LOOKING AT 640 00:36:08,326 --> 00:36:10,328 IDENTIFYING TRUE ANNULAR 641 00:36:10,328 --> 00:36:16,934 DYSFUNCTION VERSUS THIS ENTITY. 642 00:36:16,934 --> 00:36:19,570 AND THEN A RECENT PUBLICATION 643 00:36:19,570 --> 00:36:20,938 FROM THE U.K. BIO BANK LOOKING 644 00:36:20,938 --> 00:36:24,742 AT A SERIES OF PATIENTS AND 645 00:36:24,742 --> 00:36:28,680 FOUND THAT SOME LEVEL OF 646 00:36:28,680 --> 00:36:30,181 DISPLACEMENT OR DISJUNCTION CAN 647 00:36:30,181 --> 00:36:33,051 BE PRESENT IN A LARGE NUMBER OF 648 00:36:33,051 --> 00:36:35,019 PATIENTS FROM THE U.K. BIO BANK. 649 00:36:35,019 --> 00:36:39,223 IN FACT FROM NEARLY 2600 650 00:36:39,223 --> 00:36:40,158 PATIENTS INCLUDED THEY FOUND 651 00:36:40,158 --> 00:36:41,526 THAT DYSFUNCTION COULD BE 652 00:36:41,526 --> 00:36:43,227 PRESENT IN AS MANY AS 653 00:36:43,227 --> 00:36:47,365 THREE-QUARTERS OF THE CASES AND 654 00:36:47,365 --> 00:36:48,733 MOST COMMONLY IN THE INTERIOR 655 00:36:48,733 --> 00:36:50,868 AND ANTERIOR WALLS AND OUR 656 00:36:50,868 --> 00:36:51,869 UNDERSTANDING MAY HAVE 657 00:36:51,869 --> 00:36:52,570 PROGRESSED OVER THE LAST FEW 658 00:36:52,570 --> 00:36:58,309 YEARS IN SOME PART WITH THE AID 659 00:36:58,309 --> 00:37:01,245 OF CARDIAC MRI AND DYSFUNCTION 660 00:37:01,245 --> 00:37:04,415 IN THE LATERAL WALL WHICH MAY BE 661 00:37:04,415 --> 00:37:06,084 MORE IMPORTANT THAN THIS 662 00:37:06,084 --> 00:37:08,953 JUNCTION WHICH MAY BE EVIDENT OR 663 00:37:08,953 --> 00:37:11,589 APPEAR TO BE IN OTHER AREAS AND 664 00:37:11,589 --> 00:37:15,226 MAY NOT HAVE AS MUCH 665 00:37:15,226 --> 00:37:15,560 SIGNIFICANCE. 666 00:37:15,560 --> 00:37:18,296 SO I THINK A FEW QUESTIONS I 667 00:37:18,296 --> 00:37:19,464 THINK WILL BE USEFUL FOR US OVER 668 00:37:19,464 --> 00:37:21,366 THE COURSE OF THE NEXT FEW YEARS 669 00:37:21,366 --> 00:37:24,535 THE RESEARCH IS DONE TO TRY TO 670 00:37:24,535 --> 00:37:25,937 BETTER UNDERSTAND ANNULAR 671 00:37:25,937 --> 00:37:27,705 DYSFUNCTION AND UNDERSTAND THE 672 00:37:27,705 --> 00:37:30,942 TRUE DEFINITION AND IS THIS A 673 00:37:30,942 --> 00:37:39,584 MEASURE YOU DO IN DIASTOLIC AND 674 00:37:39,584 --> 00:37:42,987 WHICH WHERE NORMAL ANATOMIC 675 00:37:42,987 --> 00:37:45,623 VARIANTS AND CAN IT OCCUR 676 00:37:45,623 --> 00:37:46,290 WITHOUT MITRAL VALVE PROLAPSE OR 677 00:37:46,290 --> 00:37:48,726 IS AN ENTITY ASSOCIATED WITH 678 00:37:48,726 --> 00:37:49,594 MITRAL VALVE PROLAPSE AND THE 679 00:37:49,594 --> 00:37:57,802 QUESTION IS IS IT AN INDEPENDENT 680 00:37:57,802 --> 00:38:00,872 SUBSTRATE FOR ARRHYTHMIC RISK 681 00:38:00,872 --> 00:38:03,608 AND DOES IT RESOLVE AFTER MITRAL 682 00:38:03,608 --> 00:38:06,677 VALVE REPAIR AND DOES ARRHYTHMIC 683 00:38:06,677 --> 00:38:09,414 RISK CORRECT AFTER REPAIR? 684 00:38:09,414 --> 00:38:11,015 THAT'S IMPORTANT TO ASK. 685 00:38:11,015 --> 00:38:16,254 I'LL SHIFT THE FOCUS TO TALK 686 00:38:16,254 --> 00:38:20,958 ABOUT THIS PUBLICATION IN 2015. 687 00:38:20,958 --> 00:38:23,594 AN AUTOPSY SERIES OF PATIENTS 688 00:38:23,594 --> 00:38:30,268 FROM THE BENITO REGION OF ITALY 689 00:38:30,268 --> 00:38:33,738 OF PATIENT WHO'S SUFFERED SUDDEN 690 00:38:33,738 --> 00:38:35,573 DEATH AND LOOKED AT THE 691 00:38:35,573 --> 00:38:43,147 AUTOPSIES OF THE PATIENTS. 692 00:38:43,147 --> 00:38:43,915 MITRAL VALVE PROLAPSE WAS THE 693 00:38:43,915 --> 00:38:47,585 ONLY THING IDENTIFIED IN 70% OF 694 00:38:47,585 --> 00:38:54,125 THE CASES AND 13% OF THE WOMEN 695 00:38:54,125 --> 00:38:58,663 THAT SUFFERED SUDDEN CARDIAC 696 00:38:58,663 --> 00:38:59,464 DEATH IN THE REGISTRY. 697 00:38:59,464 --> 00:39:04,836 MOST CASES WERE MITRAL VALVE 698 00:39:04,836 --> 00:39:08,172 PROLAPSE. 699 00:39:08,172 --> 00:39:11,476 AND 90% OF THE PATIENTS 700 00:39:11,476 --> 00:39:14,078 CLASSIFIED AS SOME DEATH WITH NO 701 00:39:14,078 --> 00:39:15,446 ABNORMALITY OTHER THAN MITRAL 702 00:39:15,446 --> 00:39:16,547 VALVE PROLAPSE, WHICH AGAIN WAS 703 00:39:16,547 --> 00:39:23,521 NEARLY 50 PATIENTS, THEY HAD 704 00:39:23,521 --> 00:39:25,656 HISTOLOGIC EVIDENCE OF FIBROSIS 705 00:39:25,656 --> 00:39:27,258 ON THE MUSCLES AT AUTOPSY. 706 00:39:27,258 --> 00:39:33,564 BRINGING UP THIS HYPOTHESIS THAT 707 00:39:33,564 --> 00:39:37,668 FIBROSIS MAY REPRESENT THE 708 00:39:37,668 --> 00:39:43,741 ANATOMIC SUBSTRATE IN 709 00:39:43,741 --> 00:39:44,041 ARRHYTHMIAS. 710 00:39:44,041 --> 00:39:47,578 THE STUDY A GROUP DID WAS 711 00:39:47,578 --> 00:39:57,188 LOOKING AT THE PART BY AUTOPSY. 712 00:39:57,188 --> 00:40:03,594 AND THE WAY TO IDENTIFY FIBROSIS 713 00:40:03,594 --> 00:40:07,598 IN THE CARDIUM IS ENHANCEMENT 714 00:40:07,598 --> 00:40:13,738 MRI AND WE'VE SEEN IT EVOLVE 715 00:40:13,738 --> 00:40:24,215 SINCE ITS FIRST DEVELOPMENT. 716 00:40:35,693 --> 00:40:41,332 AND THIS IS AN EX VIVO IMAGING 717 00:40:41,332 --> 00:40:41,532 MODEL. 718 00:40:41,532 --> 00:40:44,402 AND LOOKING AT THE HISTOLOGIC ON 719 00:40:44,402 --> 00:40:46,704 THE LEFT AND ENHANCED MRI ON THE 720 00:40:46,704 --> 00:40:48,005 RIGHT YOU CAN SEE HOW CLOSELY 721 00:40:48,005 --> 00:40:51,876 THEY MIRROR AND TRACK EACH 722 00:40:51,876 --> 00:40:56,881 OTHER. 723 00:40:56,881 --> 00:40:59,850 IF WE EMPLOY THIS TECHNIQUE TO 724 00:40:59,850 --> 00:41:04,322 LOOK AT THIS FIBROSIS SUBSTRATE, 725 00:41:04,322 --> 00:41:05,489 WHAT DO WE SEE? 726 00:41:05,489 --> 00:41:07,291 THIS IS A PUBLICATION FROM A FEW 727 00:41:07,291 --> 00:41:08,626 YEARS AGO FROM OUR GROUP WHERE 728 00:41:08,626 --> 00:41:11,596 WE LOOKED AT PATIENTS WHO 729 00:41:11,596 --> 00:41:14,198 PRESENTED WITH MITRAL VALVE 730 00:41:14,198 --> 00:41:15,333 PROLAPSE AND COMPARED THEM TO A 731 00:41:15,333 --> 00:41:20,471 GROUP OF PATIENTS WITH PRIMARY 732 00:41:20,471 --> 00:41:21,205 MR WITHOUT MITRAL VALVE 733 00:41:21,205 --> 00:41:21,472 PROLAPSE. 734 00:41:21,472 --> 00:41:24,542 HERE'S A CASE WHERE YOU NOTICE 735 00:41:24,542 --> 00:41:25,943 IN THE LATERAL WALL 736 00:41:25,943 --> 00:41:27,011 CORRESPONDING TO WHAT WAS SEEN 737 00:41:27,011 --> 00:41:29,313 ON THE AUTOPSY STUDY, THERE'S 738 00:41:29,313 --> 00:41:33,184 EVIDENCE OF HYPER ENHANCEMENT WE 739 00:41:33,184 --> 00:41:37,021 SEE IN THE BASAL AND THEN 740 00:41:37,021 --> 00:41:46,030 INTRALATERAL WALL AND THE MID 741 00:41:46,030 --> 00:41:48,232 MITOCARDIAL PATTERN OF 742 00:41:48,232 --> 00:41:48,633 ENHANCEMENT. 743 00:41:48,633 --> 00:41:51,102 IN THIS SERIES WHEN WE COMPARED 744 00:41:51,102 --> 00:41:54,505 THE LEFT HAND GROUP THE ONES IN 745 00:41:54,505 --> 00:41:59,710 BLUE WITH THE PATIENTS WITH 746 00:41:59,710 --> 00:42:04,281 MITRAL VALVE PROLAPSE AND THOSE 747 00:42:04,281 --> 00:42:05,349 WITHOUT MITRAL VALVE PROLAPSE 748 00:42:05,349 --> 00:42:10,388 AND THERE WERE AREAS WHERE IT 749 00:42:10,388 --> 00:42:14,358 WAS EVIDENCE IN THE DELAYED 750 00:42:14,358 --> 00:42:20,131 ENHANCEMENT MRI AND IN THE BASAL 751 00:42:20,131 --> 00:42:21,399 INTRALATERAL WALL AGAIN 752 00:42:21,399 --> 00:42:22,233 CORRESPONDING WHAT WAS SEEN ON 753 00:42:22,233 --> 00:42:25,569 THE HISTOLOGIC STUDIES AND ALSO 754 00:42:25,569 --> 00:42:27,605 NOTICE COMPARED TO A GROUP OF 755 00:42:27,605 --> 00:42:30,041 PATIENTS THAT HAVE A SIMILAR 756 00:42:30,041 --> 00:42:34,345 DEGREE OF MITRAL REGURGITATION 757 00:42:34,345 --> 00:42:37,915 THE PREVALENCE IS HIGHER IN THE 758 00:42:37,915 --> 00:42:38,149 SEGMENT. 759 00:42:38,149 --> 00:42:42,086 THIS STUDY PROVIDES ONE LEVEL OF 760 00:42:42,086 --> 00:42:44,155 EVIDENCE OF FIBROSIS THAT OCCURS 761 00:42:44,155 --> 00:42:49,293 UNIQUE TO MITRAL VALVE PROLAPSE 762 00:42:49,293 --> 00:42:52,229 AND LOCALIZED PRIMARILY TO THESE 763 00:42:52,229 --> 00:42:58,436 ENTINTERIOR AND INTRALATERAL WA 764 00:42:58,436 --> 00:43:02,039 SEGMENTS. 765 00:43:02,039 --> 00:43:03,607 THIS SHOWED THE RELATIONSHIP 766 00:43:03,607 --> 00:43:07,578 BETWEEN THE PREVALENCE OF 767 00:43:07,578 --> 00:43:12,850 FIBROSIS IN THE COHORT AND THE 768 00:43:12,850 --> 00:43:23,094 SEVERITY OF MIGTRAL REGIRTHTATIN 769 00:43:23,094 --> 00:43:30,101 -- REGURGITATION AND SEE 770 00:43:30,101 --> 00:43:35,573 PATIENTS WITH SEVERE MR AND 771 00:43:35,573 --> 00:43:36,273 MITRAL VALVE PROLAPSE ALMOST 772 00:43:36,273 --> 00:43:38,409 HALF HAD EVIDENCE WITH DELAYED 773 00:43:38,409 --> 00:43:40,344 ENHANCEMENT MRI AND IN THE 774 00:43:40,344 --> 00:43:42,213 CONTROL GROUP WITHOUT MITRAL 775 00:43:42,213 --> 00:43:43,047 VALVE PROLAPSE THE OVER ALL 776 00:43:43,047 --> 00:43:46,217 PREVALENCE WAS LOWER AND NOT 777 00:43:46,217 --> 00:43:47,651 RELATED TO SEVERITY OF MITRAL 778 00:43:47,651 --> 00:43:57,895 REGURGITATION. 779 00:43:58,395 --> 00:44:00,998 WE LOOKED AT ARRHYTHMIC EVENTS 780 00:44:00,998 --> 00:44:02,833 AND WHAT WE NOTICED WAS THE 781 00:44:02,833 --> 00:44:05,236 RIGHT HAND BAR WERE THOSE 782 00:44:05,236 --> 00:44:10,107 PATIENTS WITH MITRAL VALVE 783 00:44:10,107 --> 00:44:13,477 PROLAPSE AND SCAR AND THE 784 00:44:13,477 --> 00:44:14,712 INCIDENTS OF ARRHYTHMIC EVENTS 785 00:44:14,712 --> 00:44:17,615 WAS HIGHER IN THAT GROUP OF 786 00:44:17,615 --> 00:44:20,985 PATIENTS THAN THOSE WITH MITRAL 787 00:44:20,985 --> 00:44:22,119 VALVE PROLAPSE WITH NO EVIDENCE 788 00:44:22,119 --> 00:44:26,323 OF FIBROSIS ON DELAYED 789 00:44:26,323 --> 00:44:28,292 ENHANCEMENT MRI OR THE CONTROL 790 00:44:28,292 --> 00:44:29,927 GROUP WITHOUT MITRAL VALVE 791 00:44:29,927 --> 00:44:30,194 PROLAPSE. 792 00:44:30,194 --> 00:44:34,498 SINCE THE OVER ALL NUMBER OF 793 00:44:34,498 --> 00:44:37,301 EVENTS WAS SMALL, MULTI-VARIATE 794 00:44:37,301 --> 00:44:40,271 ANALYSIS COULD NOT BE DONE BUT 795 00:44:40,271 --> 00:44:41,806 THERE WAS PRESENCE OF FIBROSIS 796 00:44:41,806 --> 00:44:45,810 AND THE ETIOLOGY OF THE MITRAL 797 00:44:45,810 --> 00:44:46,977 REGURGITATION WERE THE FACTORS 798 00:44:46,977 --> 00:44:51,582 ASSOCIATED WITH THE INCREASED 799 00:44:51,582 --> 00:44:54,151 ODDS RATIO OF THE ARRHYTHMIC 800 00:44:54,151 --> 00:45:01,258 EVENT. 801 00:45:01,258 --> 00:45:05,162 AFTER THAT PUBLICATION FROM A 802 00:45:05,162 --> 00:45:06,230 FRENCH GROUP WHERE THEY LOOKED 803 00:45:06,230 --> 00:45:10,034 AT DATA FROM TWO COHORT OR TWO 804 00:45:10,034 --> 00:45:13,204 CENTERS AND BEEN LOOKED TO 805 00:45:13,204 --> 00:45:19,176 IDENTIFY FIBROSIS SUBSTRATE IN 806 00:45:19,176 --> 00:45:20,611 PATIENTS WITH MITRAL VALVE 807 00:45:20,611 --> 00:45:22,246 PROLAPSE AND INCREASING 808 00:45:22,246 --> 00:45:23,647 REGURGITATION WAS ASSOCIATED 809 00:45:23,647 --> 00:45:27,484 WITH THE INCREASED PREVALENCE OF 810 00:45:27,484 --> 00:45:29,620 HAVING FIBROSIS BY DELAYED 811 00:45:29,620 --> 00:45:31,589 ENHANCEMENT MRI IN THE COHORT 812 00:45:31,589 --> 00:45:34,525 AND LOCALIZED IT TO A SIMILAR 813 00:45:34,525 --> 00:45:42,566 REGION AROUND THE BASAL 814 00:45:42,566 --> 00:45:47,204 INFRALATERAL WALL AND THEN ON 815 00:45:47,204 --> 00:45:51,542 LONGITUDINAL FOLLOW-UP THEY 816 00:45:51,542 --> 00:45:56,413 LOOKED AT EMBOLISM AND 817 00:45:56,413 --> 00:46:00,918 ARRHYTHMIAS AND THOSE WITH 818 00:46:00,918 --> 00:46:03,053 EVIDENCE OF FIBROSIS BY MRI HAD 819 00:46:03,053 --> 00:46:04,355 A WORSE EVENT PRESURVIVAL THAN 820 00:46:04,355 --> 00:46:08,359 THOSE WITH PROLAPSE BUT NO 821 00:46:08,359 --> 00:46:14,732 EVIDENCE OF FIBROSIS BY MRI. 822 00:46:14,732 --> 00:46:16,200 THIS WAS ANOTHER PUBLICATION 823 00:46:16,200 --> 00:46:18,135 THAT CAME OUT A YEAR AFTER THE 824 00:46:18,135 --> 00:46:21,805 PRIOR ONE AND THIS WAS A 825 00:46:21,805 --> 00:46:23,607 MULTICENTER RETROSPECTIVE 826 00:46:23,607 --> 00:46:27,144 EUROPEAN COHORT LOOKING AT CLOSE 827 00:46:27,144 --> 00:46:30,114 TO 500 PATIENTS FROM DIFFERENT 828 00:46:30,114 --> 00:46:30,447 SITES. 829 00:46:30,447 --> 00:46:32,683 THE COMPOSITE END POINT WAS 830 00:46:32,683 --> 00:46:38,455 SUDDEN DEATH OR SUSTAINED VP OR 831 00:46:38,455 --> 00:46:40,624 UNEXPLAINED SYNCOPE AND 832 00:46:40,624 --> 00:46:42,192 STRATIFYING BY ABSENCE OR 833 00:46:42,192 --> 00:46:45,262 PRESENCE OF MRI AND NOTICED THE 834 00:46:45,262 --> 00:46:47,298 PATIENTS WITH MITRAL VALVE 835 00:46:47,298 --> 00:46:51,602 PROLAPSE OR FIBROSIS HAD LOWER 836 00:46:51,602 --> 00:46:53,704 SURVIVAL COMPARED TO PATIENTS 837 00:46:53,704 --> 00:46:54,271 WITH MITRAL VALVE PROLAPSE 838 00:46:54,271 --> 00:46:57,308 WITHOUT EVIDENCE OF FIBROSIS AND 839 00:46:57,308 --> 00:47:03,580 DIDN'T SEE MUCH IN THE WAY OF 840 00:47:03,580 --> 00:47:08,352 SEPARATION OF THE DISRUPTION. 841 00:47:08,352 --> 00:47:10,087 THEN I'LL SHARE RECENT DATA FROM 842 00:47:10,087 --> 00:47:12,456 OUR SITE PUBLISHED OR PRESENTED 843 00:47:12,456 --> 00:47:14,658 AT AHA RECENTLY. 844 00:47:14,658 --> 00:47:19,463 THIS IS NOW LONGITUDINAL 845 00:47:19,463 --> 00:47:23,434 FOLLOW-UP ON 550 PATIENTS AND A 846 00:47:23,434 --> 00:47:26,003 LITTLE OVER FOUR YEARS AND 847 00:47:26,003 --> 00:47:27,171 EQUALLY DIVIDED BETWEEN MEN AND 848 00:47:27,171 --> 00:47:27,404 WOMEN. 849 00:47:27,404 --> 00:47:30,908 HERE NOW WE HAD A TOTAL OF 58 850 00:47:30,908 --> 00:47:32,142 COMPOSITE EVENTS AND THE 851 00:47:32,142 --> 00:47:34,445 COMPOSITE HERE WAS SUDDEN DEATH, 852 00:47:34,445 --> 00:47:39,516 AVOIDED SUDDEN DEATH OR 853 00:47:39,516 --> 00:47:41,085 SUSTAINED VENTRICULAR CARDIAC 854 00:47:41,085 --> 00:47:44,355 WITH REPLACEMENT OR PROCEDURE. 855 00:47:44,355 --> 00:47:46,423 AND THE PRESENCE OR ABSENCE OF 856 00:47:46,423 --> 00:47:50,894 LGE IN THE COHORT OF PATIENTS 857 00:47:50,894 --> 00:47:52,563 WITH MITRAL VALVE PROLAPSE 858 00:47:52,563 --> 00:47:54,898 SEEMED TO SEPARATE THOSE LIKELY 859 00:47:54,898 --> 00:47:56,834 TO HAVE AN EVENT VERSUS THOSE 860 00:47:56,834 --> 00:48:01,538 UNLIKELY TO HAVE AN EVENT WITH A 861 00:48:01,538 --> 00:48:03,374 HAZARD OF EVENTS IN MITRAL VALVE 862 00:48:03,374 --> 00:48:06,243 PROLAPSE WITH EVIDENCE OF 863 00:48:06,243 --> 00:48:12,249 FIBROSIS BY DELAYED ENHANCEMENT 864 00:48:12,249 --> 00:48:13,217 MRI. 865 00:48:13,217 --> 00:48:14,952 INTERESTINGLY IN THE COHORT 866 00:48:14,952 --> 00:48:17,154 DESPITE THE PREVALENCE OR SEX 867 00:48:17,154 --> 00:48:18,522 PREVALENCE WITH THE GROUP WAS 868 00:48:18,522 --> 00:48:22,326 EQUAL, 50% MEN AND 50% WOMEN, 869 00:48:22,326 --> 00:48:25,029 MOST EVENTS IN FACT 75% OF 870 00:48:25,029 --> 00:48:31,068 EVENTS OCCUR IN WOMEN. 871 00:48:31,068 --> 00:48:34,338 THIS SHOWS STRATIFICATION OF 872 00:48:34,338 --> 00:48:37,341 LIKELIHOOD OF A COMPOSITE EVENT 873 00:48:37,341 --> 00:48:39,810 STRATIFIED BOTH BY SEX AND 874 00:48:39,810 --> 00:48:41,245 PREVALENCE OF LGE. 875 00:48:41,245 --> 00:48:46,350 WHAT YOU'LL NOTICE IF YOU LOOK 876 00:48:46,350 --> 00:48:50,154 THET GREEN DASH LINE WITH MEN 877 00:48:50,154 --> 00:48:55,592 WITH NO FIBROSIS WITH MRI HAD 878 00:48:55,592 --> 00:48:59,596 LOWEST COMPOSITE EVENTS OR 879 00:48:59,596 --> 00:49:02,066 MIDDLE IS WOMEN WITHOUT FIBROSIS 880 00:49:02,066 --> 00:49:03,267 WHERE THERE WAS AN IMMEDIATE 881 00:49:03,267 --> 00:49:05,536 COMPOSITE EVENT AND THE NUMBER 882 00:49:05,536 --> 00:49:09,173 OF EVENTS OCCURRED IN WOMEN WITH 883 00:49:09,173 --> 00:49:10,607 EVIDENCE OF FIBROSIS EVIDENT ON 884 00:49:10,607 --> 00:49:16,346 MRI. 885 00:49:16,346 --> 00:49:20,717 AND AGAIN WITH THE LARGER NUMBER 886 00:49:20,717 --> 00:49:22,886 OF EVENTS ALLOWED FOR COVARIATES 887 00:49:22,886 --> 00:49:27,391 AND WE ADJUSTED FOR SEVERITY AND 888 00:49:27,391 --> 00:49:30,360 PROLAPSE AND ADJUST FOR MITRAL 889 00:49:30,360 --> 00:49:31,361 ANNULAR DYSFUNCTION SEVERITY AND 890 00:49:31,361 --> 00:49:34,264 THE TWO FACTORS THAT REMAIN 891 00:49:34,264 --> 00:49:34,932 INDEPENDENTLY SIGNIFICANT WERE 892 00:49:34,932 --> 00:49:39,103 PRESENCE OF LGE OR FIBROSIS 893 00:49:39,103 --> 00:49:41,672 DETECTED BY MRI WITH OVER 894 00:49:41,672 --> 00:49:46,043 THREE-FOLD HIGHER HAZARD AND 895 00:49:46,043 --> 00:49:49,713 FEMALE SEX WITH A THREEFOLD 896 00:49:49,713 --> 00:49:51,682 HIGHER HAZARD OF COMPOSITE 897 00:49:51,682 --> 00:49:51,915 EVENTS. 898 00:49:51,915 --> 00:49:55,619 THE OTHER QUESTION THAT COMES UP 899 00:49:55,619 --> 00:49:58,622 IS MOST THE DATA SO AS FAR WITH 900 00:49:58,622 --> 00:50:03,327 REGARD TO DELAYED ENHANCEMENT 901 00:50:03,327 --> 00:50:09,366 MRI WITH FIBROSIS USED A 902 00:50:09,366 --> 00:50:09,900 TECHNIQUE EXCELLENT FOR 903 00:50:09,900 --> 00:50:12,769 IDENTIFYING FIBROSIS WITHIN THE 904 00:50:12,769 --> 00:50:13,203 SEGMENTS. 905 00:50:13,203 --> 00:50:15,606 I'LL SHOW YOU NOW THERE'S A 906 00:50:15,606 --> 00:50:18,142 NEWER TECHNIQUE WE'RE ABLE TO 907 00:50:18,142 --> 00:50:20,310 EMPLOY A DARK BLOOD TECHNIQUE 908 00:50:20,310 --> 00:50:21,912 WE'VE BEEN USING SEVERAL YEARS 909 00:50:21,912 --> 00:50:26,483 WHICH IS VERY GOOD FOR 910 00:50:26,483 --> 00:50:31,288 IDENTIFYING PAPULAR MUSCLE 911 00:50:31,288 --> 00:50:34,091 FIBROSIS AND MAY BE NOT CLEARLY 912 00:50:34,091 --> 00:50:35,392 EVIDENT BUT THE DARK TECHNIQUE 913 00:50:35,392 --> 00:50:38,061 WHERE IT SUPPRESSES IT IT'S ABLE 914 00:50:38,061 --> 00:50:41,098 TO ALLOW YOU TO ASSESS FOR 915 00:50:41,098 --> 00:50:44,568 FIBROSIS WITHIN THE PAPULARRY 916 00:50:44,568 --> 00:50:45,936 MUSCLES AND THE QUESTION IS WE 917 00:50:45,936 --> 00:50:48,605 NEED TO PROBABLY LOOK AT A 918 00:50:48,605 --> 00:50:50,040 COMBINATION OF THE FIBROSIS 919 00:50:50,040 --> 00:51:00,584 WITHIN THE WALL AND WITHIN THE 920 00:51:08,091 --> 00:51:18,302 PAPULARMUSCLES. 921 00:51:19,269 --> 00:51:20,337 AND WHAT ABOUT INTERSTITIAL 922 00:51:20,337 --> 00:51:22,372 FIBROSIS WHICH MAY BE A MORE 923 00:51:22,372 --> 00:51:32,649 DYNAMIC PROCESS. 924 00:51:37,120 --> 00:51:39,990 WE DO MAPPING TO ALLOW THE 925 00:51:39,990 --> 00:51:43,594 ESTIMATION OF THE VOLUME 926 00:51:43,594 --> 00:51:46,697 REFRACTION WHICH HAS ASSOCIATION 927 00:51:46,697 --> 00:51:49,066 WITH INTERSTITIAL BURDEN BASED 928 00:51:49,066 --> 00:51:59,443 ON HISTOLOGY SAMPLING. 929 00:52:12,789 --> 00:52:15,425 AND THIS IS A PUBLICATION FROM 930 00:52:15,425 --> 00:52:17,160 OUR GROUP YEARS AGO WHERE WE 931 00:52:17,160 --> 00:52:18,962 LOOKED AT PATIENTS WITH MITRAL 932 00:52:18,962 --> 00:52:23,367 VALVE PROLAPSE AND THE CONTROL 933 00:52:23,367 --> 00:52:26,103 GROUP AND NOTICED ACROSS THE 934 00:52:26,103 --> 00:52:28,972 SPECTRUM OF SEVERITY THERE'S AN 935 00:52:28,972 --> 00:52:30,907 INCREASING IN VOLUME REFRACTION 936 00:52:30,907 --> 00:52:32,643 THAT SEEMS TO BE RELATED OR 937 00:52:32,643 --> 00:52:34,544 SEEMS TO BE INDEPENDENT OF 938 00:52:34,544 --> 00:52:37,414 SEVERITY OF ETIOLOGY WHETHER 939 00:52:37,414 --> 00:52:39,216 MITRAL VALVE PROLAPSE OR 940 00:52:39,216 --> 00:52:39,549 NON-PROLAPSE. 941 00:52:39,549 --> 00:52:46,323 AND I'LL WRAP UP IN A COUPLE 942 00:52:46,323 --> 00:52:47,758 SECONDS. 943 00:52:47,758 --> 00:52:50,394 THERE'S MORE RECENT WORK FROM A 944 00:52:50,394 --> 00:52:56,300 GROUP AND UCSF WHERE THEY 945 00:52:56,300 --> 00:52:59,603 PUBLISHED RECENTLY THE THOSE 946 00:52:59,603 --> 00:53:01,271 WITH THE ARRHYTHMIC PHENOTYPE 947 00:53:01,271 --> 00:53:03,640 VERSUS THOSE THAT DO NOT AND AT 948 00:53:03,640 --> 00:53:10,347 LEAST WITH REGARD TO THE ARE 949 00:53:10,347 --> 00:53:14,318 AREEGE -- AREEGE DEF 950 00:53:36,840 --> 00:53:39,076 AAND THINKING HOW TO APPROACH 951 00:53:39,076 --> 00:53:41,978 THE ISSUE OF ARRHYTHMIC MVP 952 00:53:41,978 --> 00:53:43,480 FIBROSIS REPRESENTS ONE 953 00:53:43,480 --> 00:53:45,615 SUBSTRATE BUT IS PROBABLY ITSELF 954 00:53:45,615 --> 00:53:46,350 NOT THE ONLY FACTOR. 955 00:53:46,350 --> 00:53:49,753 SO WE NEED TO TAKE A 956 00:53:49,753 --> 00:53:51,388 MULTI-FACTORIAL APPROACH AND I'M 957 00:53:51,388 --> 00:53:53,390 EXCITED ABOUT THIS 958 00:53:53,390 --> 00:53:55,192 MULTI-MODALITY APPROACH BEING 959 00:53:55,192 --> 00:53:59,696 EMBARKED UPON HERE. 960 00:53:59,696 --> 00:54:03,967 AND ULTIMATELY BECAUSE I'LL 961 00:54:03,967 --> 00:54:06,336 SHARE WITH YOU QUICKLY A PROJECT 962 00:54:06,336 --> 00:54:08,305 ONGOING AT HOUSTON METHODIST 963 00:54:08,305 --> 00:54:10,741 WITH A TEAM PHENOTYPING COHORT 964 00:54:10,741 --> 00:54:17,814 ENROLLING PATIENTS WITH MITRAL 965 00:54:17,814 --> 00:54:21,985 VALVE PROLAPSE AND INTERSTITIAL 966 00:54:21,985 --> 00:54:26,923 FIBROSIS AND MONITORING TO 967 00:54:26,923 --> 00:54:30,427 QUANTIFY ARRHYTHMIC BURDEN AND 968 00:54:30,427 --> 00:54:41,371 BLOOD SAMPLIING SAMPLE UTILIZED 969 00:54:43,640 --> 00:54:44,908 PROTEOMIC PLATFORMS AS WELL. 970 00:54:44,908 --> 00:54:51,448 AND LASTLY THE FINAL AIM WITH 971 00:54:51,448 --> 00:54:54,418 THIS PROJECT IS TO COMBINE A 972 00:54:54,418 --> 00:54:56,920 COHORT OF NEARLY 2,000 CARDIAC 973 00:54:56,920 --> 00:54:58,955 MRI STUDIES DONE ACROSS SEVERAL 974 00:54:58,955 --> 00:55:02,392 SITES AND TRY TO IDENTIFY A RISK 975 00:55:02,392 --> 00:55:04,694 PREDICTION MODEL FOR MITRAL 976 00:55:04,694 --> 00:55:06,329 VALVE PROLAPSE USING CARDIAC MRI 977 00:55:06,329 --> 00:55:12,135 AS POTENTIALLY A SEN IS -- 978 00:55:12,135 --> 00:55:12,536 CENTRAL MARKER. 979 00:55:12,536 --> 00:55:13,804 THANK YOU FOR YOUR ATTENTION. 980 00:55:13,804 --> 00:55:17,207 >> THANK YOU, DIPAN, THAT WAS 981 00:55:17,207 --> 00:55:17,474 EXCELLENT. 982 00:55:17,474 --> 00:55:20,310 WE RECEIVED A QUESTION FROM THE 983 00:55:20,310 --> 00:55:21,711 VIDEOCAST JUST AFTER JUDY'S TALK 984 00:55:21,711 --> 00:55:24,214 BUT IT'S KIND OF A GENERAL 985 00:55:24,214 --> 00:55:26,416 QUESTION SO I'D LIKE TO DEFER 986 00:55:26,416 --> 00:55:27,617 THAT UNTIL THE DISCUSSION AT 987 00:55:27,617 --> 00:55:28,518 THEN OF THE SESSION. 988 00:55:28,518 --> 00:55:31,087 IN THE MEANTIME DOES ANYONE HAVE 989 00:55:31,087 --> 00:55:34,357 QUESTIONS OR COMMENTS ABOUT 990 00:55:34,357 --> 00:55:36,426 DIPAN'S ? 991 00:55:36,426 --> 00:55:37,594 -- PRESENTATION. 992 00:55:37,594 --> 00:55:40,931 >> THIS IS MAURICIO. 993 00:55:40,931 --> 00:55:43,834 CAN YOU COMMENT ON THE SPECIAL 994 00:55:43,834 --> 00:55:49,172 AND TEMPORAL RESOLUTION OF MRI 995 00:55:49,172 --> 00:55:51,508 BECAUSE IN THE DESCRIPTION OF 996 00:55:51,508 --> 00:55:54,344 THE ANATOMIC FEATURE OF THE 997 00:55:54,344 --> 00:55:57,647 MITRAL VALVE I'M A BIG BELIEVER 998 00:55:57,647 --> 00:55:59,549 IN THE FIBROSIS AND METRICS. 999 00:55:59,549 --> 00:56:02,185 I'M A LITTLE CONCERNED ABOUT THE 1000 00:56:02,185 --> 00:56:05,422 ABILITY TO SEE IN TIME ALL THE 1001 00:56:05,422 --> 00:56:08,091 STRUCTURE AND IN PARTICULAR THE 1002 00:56:08,091 --> 00:56:10,360 ANNULUS AND I'M CONCERNED A LOT 1003 00:56:10,360 --> 00:56:14,531 OF THINGS ON THE MAD IN THE MRI 1004 00:56:14,531 --> 00:56:17,934 LITERATURE MAY BE RELATED TO 1005 00:56:17,934 --> 00:56:19,569 DIFFICULT ASSESSMENT OF THE 1006 00:56:19,569 --> 00:56:20,570 MITRAL ANNULAR STRUCTURE. 1007 00:56:20,570 --> 00:56:22,372 >> THAT'S A GET QUESTION. 1008 00:56:22,372 --> 00:56:26,776 IF YOU LOOK AT WHAT THE SCMR 1009 00:56:26,776 --> 00:56:27,944 GUIDELINES FOR SPATIAL AND 1010 00:56:27,944 --> 00:56:29,779 TEMPORAL RESOLUTION FOR IMAGES 1011 00:56:29,779 --> 00:56:34,718 AN IN MANY LABS DO HIGHER 1012 00:56:34,718 --> 00:56:35,685 SPATIAL RESOLUTION THAN THAT BUT 1013 00:56:35,685 --> 00:56:39,990 WANT TO TARGET BETWEEN IT 25 TO 1014 00:56:39,990 --> 00:56:41,992 30 MILLISECOND RESOLUTION AND 1015 00:56:41,992 --> 00:56:43,894 SPATIAL RESOLUTION IS IN THE 1016 00:56:43,894 --> 00:56:47,597 ORDER OF ONE AND A HALF TO TWO 1017 00:56:47,597 --> 00:56:49,733 MILLIM 1018 00:56:49,733 --> 00:56:50,033 MILLIMETERS. 1019 00:56:50,033 --> 00:56:51,468 I AGREE ONE THING IS WHEN WE 1020 00:56:51,468 --> 00:56:54,838 LOOK AT THE CASES FOR MAD IT'S 1021 00:56:54,838 --> 00:56:57,307 TO GO FRAME BY FRAME THROUGH 1022 00:56:57,307 --> 00:56:59,509 THIS AND TRY TO SEPARATE OUT 1023 00:56:59,509 --> 00:57:01,444 ESPECIALLY WHERE THE LEAFLET 1024 00:57:01,444 --> 00:57:04,915 SEEMS TO BE HUGGING UP AGAINST 1025 00:57:04,915 --> 00:57:07,183 THE WALL WHICH ON A FRAME BY 1026 00:57:07,183 --> 00:57:07,817 FRAME ANALYSIS YOU CAN GET SOME 1027 00:57:07,817 --> 00:57:11,521 ASSESSMENT OF THAT. 1028 00:57:11,521 --> 00:57:15,659 BUT I AGREE WITH YOU IF WE HAVE 1029 00:57:15,659 --> 00:57:18,028 ULTRA HIGH IMAGING WHICH NO ONE 1030 00:57:18,028 --> 00:57:19,162 HAS AT THIS POINT WOULD HELP 1031 00:57:19,162 --> 00:57:23,033 FURTHER SORT THIS OUT. 1032 00:57:23,033 --> 00:57:28,138 >> I JUST WANT TO COMMENT ON 1033 00:57:28,138 --> 00:57:30,507 BUILDING A COMMUNITY OF INTEREST 1034 00:57:30,507 --> 00:57:33,176 IN THIS AREA AS THIS WORKSHOP IS 1035 00:57:33,176 --> 00:57:34,578 DOING. 1036 00:57:34,578 --> 00:57:39,115 I WANTED TO SAY YOUR PAPER IN 1037 00:57:39,115 --> 00:57:40,350 2018 ABOUT THE FIBROSIS. 1038 00:57:40,350 --> 00:57:43,520 OF COURSE THE IDEA HAD BEEN 1039 00:57:43,520 --> 00:57:44,354 INTRODUCED WITH DATA FROM THE 1040 00:57:44,354 --> 00:57:47,824 GROUP AND PATHOLOGY BEFORE BUT 1041 00:57:47,824 --> 00:57:49,626 THE FIRST LARGE GROUP SHOWING 1042 00:57:49,626 --> 00:57:53,830 THE PREVALENCE OF THIS MITRAL 1043 00:57:53,830 --> 00:57:55,599 CARDIO FIBROSIS STIMULATED THE 1044 00:57:55,599 --> 00:57:57,467 THINKING OF OUR GROUP TO MOVE 1045 00:57:57,467 --> 00:58:00,670 AHEAD AND EXPLORE MECHANISTIC 1046 00:58:00,670 --> 00:58:01,805 POSSIBILITIES AND PROGNOSTIC 1047 00:58:01,805 --> 00:58:03,306 IMPLICATIONS. 1048 00:58:03,306 --> 00:58:06,643 I WANTED TO COMPLIMENT YOU ON 1049 00:58:06,643 --> 00:58:07,577 STARTING THE BALL MOVEMENT IN 1050 00:58:07,577 --> 00:58:09,079 GOOD DIRECTIONS. 1051 00:58:09,079 --> 00:58:11,381 >> THANK YOU VERY MUCH, BOB. 1052 00:58:11,381 --> 00:58:13,249 I NEED IT SAY NOTHING FURTHER. 1053 00:58:13,249 --> 00:58:15,051 THE ENTIRE DEFINITION ABOUT 1054 00:58:15,051 --> 00:58:18,855 PROLAPSE IS CREDITED TO YOU IN 1055 00:58:18,855 --> 00:58:20,256 THE FIELD COULD NOT HAVE MOVED 1056 00:58:20,256 --> 00:58:22,359 FORWARD WITHOUT YOUR 1057 00:58:22,359 --> 00:58:27,597 CONTRIBUTIONS MANY YEARS AGO. 1058 00:58:27,597 --> 00:58:34,337 >> THANK YOU. 1059 00:58:34,337 --> 00:58:44,714 THIERRY, YOU'RE MUTED. 1060 00:59:06,503 --> 00:59:08,038 >> IN THE MEANTIME, JONATHAN, DO 1061 00:59:08,038 --> 00:59:10,407 YOU HAVE A QUESTION? 1062 00:59:10,407 --> 00:59:11,908 >> GREAT TALK AND INTERESTING 1063 00:59:11,908 --> 00:59:13,743 DATA IN TERMS OF THINKING ABOUT 1064 00:59:13,743 --> 00:59:16,746 THIS AND THANKS TO JUDY HUNG AS 1065 00:59:16,746 --> 00:59:19,683 WELL. 1066 00:59:19,683 --> 00:59:21,851 TWO QUESTIONS RELATED TO THE 1067 00:59:21,851 --> 00:59:26,556 DATA THAT YOU PRESENTED. 1068 00:59:26,556 --> 00:59:28,358 FIRST, YOU PRESENTED CERTAINLY 1069 00:59:28,358 --> 00:59:31,227 MUCH OF THE LITERATURE THOUGH 1070 00:59:31,227 --> 00:59:33,530 THE LITERATURE IS EVOLVING AS 1071 00:59:33,530 --> 00:59:37,500 RELATED TO BOTH MITRAL ANNULAR 1072 00:59:37,500 --> 00:59:39,335 DYSFUNCTION AS WELL ENHANCEMENT 1073 00:59:39,335 --> 00:59:41,371 AS A MARKER OF ARRHYTHMIC RISK 1074 00:59:41,371 --> 00:59:44,541 IN PATIENTS WITH MITRAL VALVE 1075 00:59:44,541 --> 00:59:44,941 PROLAPSE. 1076 00:59:44,941 --> 00:59:48,845 CERTAINLY MANY STUDIES BUT NOT 1077 00:59:48,845 --> 00:59:52,348 ALL INCLUDING THE RECENT DATA 1078 00:59:52,348 --> 00:59:56,886 WHICH IS AN EXCEPTION USE 1079 00:59:56,886 --> 01:00:01,191 TELEMETRY OR MONITORING EVIDENCE 1080 01:00:01,191 --> 01:00:01,958 VENTRICULAR ATROPY AS AMYTH RICK 1081 01:00:01,958 --> 01:00:05,328 RISK AND WE LEARNED FROM OTHER 1082 01:00:05,328 --> 01:00:08,631 TRIALS THAT MONITORING EVIDENCE 1083 01:00:08,631 --> 01:00:12,402 ARRHYTHMIAS ARE NOT A SURROGATE 1084 01:00:12,402 --> 01:00:13,636 FOR ACTUAL EVENTS. 1085 01:00:13,636 --> 01:00:16,372 WHAT IS YOUR THOUGHT ON THAT 1086 01:00:16,372 --> 01:00:18,608 WITH THE MITRAL VALVE PROLAPSE 1087 01:00:18,608 --> 01:00:20,210 LITERATURE AND I HAVE A 1088 01:00:20,210 --> 01:00:22,378 FOLLOW-UP. 1089 01:00:22,378 --> 01:00:27,350 >> EXCELLENT POINT. 1090 01:00:27,350 --> 01:00:29,119 BECAUSE OF SAMPLE SIZE 1091 01:00:29,119 --> 01:00:34,124 LIMITATIONS IN A LOT OF THE 1092 01:00:34,124 --> 01:00:43,566 EARLY WORK MARKERS ARE USED FOR 1093 01:00:43,566 --> 01:00:53,143 MONITORING OF ARRHYTHMIA IF WE 1094 01:00:53,143 --> 01:00:58,348 TELL THEM WE REDUCED YOUR RISK 1095 01:00:58,348 --> 01:01:03,186 OF THIS AND THEY SAY WHAT'S MY 1096 01:01:03,186 --> 01:01:04,354 CHANCE OF DEATH AND IT'S 1097 01:01:04,354 --> 01:01:07,590 FOSTERING THE ABILITY TO DO 1098 01:01:07,590 --> 01:01:09,325 LARGER COHORTS WHICH HOPEFULLY 1099 01:01:09,325 --> 01:01:10,627 WILL BE DESIGN TO LOOK 1100 01:01:10,627 --> 01:01:12,762 SPECIFICALLY AT CLINICAL END 1101 01:01:12,762 --> 01:01:14,097 POINTS OPPOSED TO SURROGATE 1102 01:01:14,097 --> 01:01:16,166 MARKERS AND THAT MAY EXPLAIN THE 1103 01:01:16,166 --> 01:01:17,600 DIFFERENCES WE SEE ALSO BETWEEN 1104 01:01:17,600 --> 01:01:22,405 SMALL COHORTS VERSUS LARGER 1105 01:01:22,405 --> 01:01:23,573 GROUPS WHERE THERE'S MORE 1106 01:01:23,573 --> 01:01:25,175 CLINICAL OUTCOMES. 1107 01:01:25,175 --> 01:01:29,112 >> SECOND. 1108 01:01:29,112 --> 01:01:30,146 FOLLOW-UP QUESTION I'LL ASK WITH 1109 01:01:30,146 --> 01:01:34,350 REGARD TO THE DATA YOU AND 1110 01:01:34,350 --> 01:01:39,823 OTHERS PRESENTED, RELATES TO 1111 01:01:39,823 --> 01:01:42,792 DIFFERENTIAL CONCEPT BETWEEN 1112 01:01:42,792 --> 01:01:43,493 INDEPENDENT ASSOCIATIONS AND 1113 01:01:43,493 --> 01:01:46,863 LEVEL OF PRECISION TO GUIDE 1114 01:01:46,863 --> 01:01:47,063 CARE. 1115 01:01:47,063 --> 01:01:51,935 CERTAINLY WE HAVE MANY RISK 1116 01:01:51,935 --> 01:01:55,471 MARKERS FOR MANY INDEPENDENT 1117 01:01:55,471 --> 01:01:58,341 MARKERS INCLUDING ENHANCEMENT IN 1118 01:01:58,341 --> 01:02:01,811 MYOPATHY AND OTHERWISE YET 1119 01:02:01,811 --> 01:02:04,113 THERE'S A MARKED DISORDERANCE OF 1120 01:02:04,113 --> 01:02:09,219 A FINDING AND RATES. 1121 01:02:09,219 --> 01:02:12,422 ONE WOULD LOOK AT THE 1122 01:02:12,422 --> 01:02:12,722 LITERATURE. 1123 01:02:12,722 --> 01:02:15,692 HOW TO YOU COMMENT ON PREVALENCE 1124 01:02:15,692 --> 01:02:18,561 OF LGE AND EVENTS AND IN YOUR 1125 01:02:18,561 --> 01:02:21,197 OUTCOMES DATA, 6% OF PATIENTS 1126 01:02:21,197 --> 01:02:24,434 WITH EVENTS HAD NO ENHANCEMENT. 1127 01:02:24,434 --> 01:02:27,003 >> I THINK IT'S A VERY GOOD 1128 01:02:27,003 --> 01:02:27,237 POINT. 1129 01:02:27,237 --> 01:02:31,040 SO ONE IS WITH REGARD TO THE 1130 01:02:31,040 --> 01:02:33,142 OVER ALL PREVALENCE OF LGE AMONG 1131 01:02:33,142 --> 01:02:35,211 PATIENTS WITH MITRAL VALVE 1132 01:02:35,211 --> 01:02:36,079 PROLAPSE IS HIGH ENOUGH YOU SORT 1133 01:02:36,079 --> 01:02:37,714 OF CAN'T USE THIS ALONE AS A 1134 01:02:37,714 --> 01:02:39,916 MARKER TO SAY I'M GOING TO DO 1135 01:02:39,916 --> 01:02:42,652 TREATMENT ON ALL THESE PATIENTS. 1136 01:02:42,652 --> 01:02:44,754 THAT'S TOO LARGE A GROUP OF 1137 01:02:44,754 --> 01:02:45,321 PATIENTS. 1138 01:02:45,321 --> 01:02:47,590 THE WAY I THINK ABOUT THIS IS 1139 01:02:47,590 --> 01:02:49,459 THIS REPRESENTS A CENTRAL 1140 01:02:49,459 --> 01:02:50,627 SUBSTRATE BUT THERE'S OTHER 1141 01:02:50,627 --> 01:02:55,198 FEATURES THAT GO WITH THAT TO 1142 01:02:55,198 --> 01:02:56,933 INCREASE THE LIKELIHOOD THESE 1143 01:02:56,933 --> 01:02:59,569 PATIENTS MAY GO ON TO HAVE AN 1144 01:02:59,569 --> 01:03:01,671 ARRHYTHMIC EVENT AND LGE MAY NOT 1145 01:03:01,671 --> 01:03:03,373 FULLY CAPTURE ALL RISK HERE. 1146 01:03:03,373 --> 01:03:06,476 I TRIED TO HIGHLIGHT THE ONE 1147 01:03:06,476 --> 01:03:09,012 AREA WHICH IS THE DIFFERENCE 1148 01:03:09,012 --> 01:03:17,120 BETWEEN THE DEF TEF 1149 01:03:33,036 --> 01:03:34,037 PAPILLARY TISSUE AND SMALLER 1150 01:03:34,037 --> 01:03:36,773 BURDENS MAY GO UNIDENTIFIED ON 1151 01:03:36,773 --> 01:03:39,075 THE INITIAL SET OF IMAGING. 1152 01:03:39,075 --> 01:03:44,280 THANK YOU, JONATHAN, THOSE ARE 1153 01:03:44,280 --> 01:03:45,181 GREAT QUESTIONS. 1154 01:03:45,181 --> 01:03:46,416 >> CAN YOU HEAR ME NOW? 1155 01:03:46,416 --> 01:03:46,883 >> YES. 1156 01:03:46,883 --> 01:03:54,824 >> CONGRATULATIONS FOR YOUR 1157 01:03:54,824 --> 01:03:55,158 PRESENTATION. 1158 01:03:55,158 --> 01:03:56,492 I WAS VERY INTERESTED BY THE 1159 01:03:56,492 --> 01:03:59,095 STUDY AT THE AHA. 1160 01:03:59,095 --> 01:04:01,130 I DISCOVERED YOUR DATA. 1161 01:04:01,130 --> 01:04:04,567 I HAVE TWO QUESTIONS RELATED. 1162 01:04:04,567 --> 01:04:09,539 ONE TO THE OTHER. 1163 01:04:09,539 --> 01:04:11,174 AND DID YOU SELECT A SUBGROUP OF 1164 01:04:11,174 --> 01:04:16,446 PATIENTS ESPECIALLY PATIENTS 1165 01:04:16,446 --> 01:04:22,352 WITH FREE COUNT PVC AND DID YOU 1166 01:04:22,352 --> 01:04:26,022 INCLUDE PATIENTS WITH MITRAL 1167 01:04:26,022 --> 01:04:27,423 VALVE PROLAPSE DISEASE DID YOU 1168 01:04:27,423 --> 01:04:31,227 TEST BY GENETICS ETCETERA? 1169 01:04:31,227 --> 01:04:32,795 >> GREAT QUESTIONS. 1170 01:04:32,795 --> 01:04:38,001 >> THE COHORT IS PATIENTS 1171 01:04:38,001 --> 01:04:38,901 UNDERGOING A CLINICALLY 1172 01:04:38,901 --> 01:04:40,470 INDICATED SCAN. 1173 01:04:40,470 --> 01:04:43,573 THE REASON FOR THE CARDIAC MRI 1174 01:04:43,573 --> 01:04:44,440 SCAN VARIED. 1175 01:04:44,440 --> 01:04:47,577 ABOUT A THIRD WERE BECAUSE OF 1176 01:04:47,577 --> 01:04:53,516 SOME ARRHYTHMIA SYMPTOMS, P 1177 01:04:53,516 --> 01:04:59,155 PALPITATIONS AND SOME WERE FOR 1178 01:04:59,155 --> 01:05:06,896 ASSESSMENT OF REGIRTHTATION -- 1179 01:05:06,896 --> 01:05:07,663 REGURGITATION. 1180 01:05:07,663 --> 01:05:09,699 THAT HOPEFULLY ANSWERS YOUR 1181 01:05:09,699 --> 01:05:10,933 FIRST QUESTION. 1182 01:05:10,933 --> 01:05:13,269 THE SECOND QUESTION WAS WITH 1183 01:05:13,269 --> 01:05:15,571 REGARD TO SYSTEMIC ASSESSMENT 1184 01:05:15,571 --> 01:05:17,640 FOR INHERITED ARRHYTHMIAS. 1185 01:05:17,640 --> 01:05:23,046 THIS IS MORE OF A LONGITUDINAL 1186 01:05:23,046 --> 01:05:23,780 OBSERVATIONAL COHORT AND THE 1187 01:05:23,780 --> 01:05:26,749 ASSESSMENT WOULD HAVE BEEN AT 1188 01:05:26,749 --> 01:05:28,051 THE TREATING PHYSICIAN. 1189 01:05:28,051 --> 01:05:31,354 THERE'S NOT A SPECIFIC PROTOCOL 1190 01:05:31,354 --> 01:05:33,923 WHERE THEY UNDERWENT AN 1191 01:05:33,923 --> 01:05:35,591 ASSESSMENT FOR OTHER INHERITED 1192 01:05:35,591 --> 01:05:45,968 ARRHYTHMIC CONDITIONS. 1193 01:05:50,873 --> 01:05:52,508 >> THE FEMALE RELATIONSHIP WITH 1194 01:05:52,508 --> 01:05:55,244 HIGHER EVENTS, WOMEN. 1195 01:05:55,244 --> 01:06:00,650 REMIND ME HOW DID YOU CONTROL 1196 01:06:00,650 --> 01:06:02,118 FOR MITRAL VALVE ANATOMY NOT 1197 01:06:02,118 --> 01:06:05,188 JUST FOR SINGLE LEAFLET PROLAPSE 1198 01:06:05,188 --> 01:06:07,590 BUT VOLUME AND WIDTH NOT HEIGHT 1199 01:06:07,590 --> 01:06:09,892 BUT VOLUME, WIDTH AND HEIGHT OF 1200 01:06:09,892 --> 01:06:10,126 LEAFLET. 1201 01:06:10,126 --> 01:06:14,497 >> THAT'S A VERY GOOD QUESTION. 1202 01:06:14,497 --> 01:06:15,598 WE GET TO THE SEVERITY OF THE 1203 01:06:15,598 --> 01:06:21,204 PATIENTS. 1204 01:06:21,204 --> 01:06:23,573 >> IT'S THE AMOUNT OF VOLUME 1205 01:06:23,573 --> 01:06:27,510 BECAUSE VOLUME CREATES TENSION. 1206 01:06:27,510 --> 01:06:28,578 CERTAINLY MECHANISTICALLY IT'S A 1207 01:06:28,578 --> 01:06:31,180 POSSIBILITY. 1208 01:06:31,180 --> 01:06:34,383 I'M THINKING MORE ABOUT LEAFLET 1209 01:06:34,383 --> 01:06:36,552 VOLUME OPPOSED TO PROLAPSE 1210 01:06:36,552 --> 01:06:36,819 NECESSARY. 1211 01:06:36,819 --> 01:06:38,588 >> THE VOLUME OF THE LEAFLETS 1212 01:06:38,588 --> 01:06:46,762 NOT THE VOLUME OF PROLAPSES. 1213 01:06:46,762 --> 01:06:50,867 THE ANNULAR SIZE IS 26, 28 IN 1214 01:06:50,867 --> 01:06:53,302 THE ABSENCE OF SYSTOLIC MOTION 1215 01:06:53,302 --> 01:06:55,404 YOU NEED LESS LEAFLET VOLUME TO 1216 01:06:55,404 --> 01:06:58,975 FIT INSIDE THE ANNULUS WHERE IF 1217 01:06:58,975 --> 01:07:01,511 YOU'RE IN THE 34, 36, 38 AND 32 1218 01:07:01,511 --> 01:07:03,579 YOU HAVE MORE EVEN IN VALVES 1219 01:07:03,579 --> 01:07:04,847 THAT DON'T LEAK VERY MUCH. 1220 01:07:04,847 --> 01:07:07,750 >> WE HAVEN'T DONE THAT ANALYSIS 1221 01:07:07,750 --> 01:07:07,917 YET. 1222 01:07:07,917 --> 01:07:11,587 WE TRY TO QUANTIFY WHAT IS THE 1223 01:07:11,587 --> 01:07:14,891 TOTAL VOLUME OF THE LEAFLETS. 1224 01:07:14,891 --> 01:07:15,892 I HAVE OTHER PROGRAMS ONGOING 1225 01:07:15,892 --> 01:07:20,663 LOOKING AT STRAIN ON THE 1226 01:07:20,663 --> 01:07:21,297 LEAFLETS THEMSELVES WITH 1227 01:07:21,297 --> 01:07:22,031 MATHEMATICIAN COLLEGIATE THE 1228 01:07:22,031 --> 01:07:24,267 UNIVERSITY OF HOUSTON. 1229 01:07:24,267 --> 01:07:25,902 THOSE ARE EARLY PHASES RIGHT 1230 01:07:25,902 --> 01:07:26,068 NOW. 1231 01:07:26,068 --> 01:07:27,870 THOSE ARE GOOD COMMENTS AND GOOD 1232 01:07:27,870 --> 01:07:28,371 POINT. 1233 01:07:28,371 --> 01:07:29,272 >> IT'S INTERESTING. 1234 01:07:29,272 --> 01:07:34,210 IT MAY WELL BE THE LINKAGE IS 1235 01:07:34,210 --> 01:07:36,078 NOT FOR INSTANCE WHETHER THAT 1236 01:07:36,078 --> 01:07:38,447 COULD BE HORMONAL OR LATER 1237 01:07:38,447 --> 01:07:41,784 PRESENTATION OR SOME OF THE 1238 01:07:41,784 --> 01:07:43,219 THINGS WE'RE USED TO DESCRIBING 1239 01:07:43,219 --> 01:07:45,188 TO SOME DIFFERENCES, SEX 1240 01:07:45,188 --> 01:07:47,190 DIFFERENCES IN OUTCOMES IN 1241 01:07:47,190 --> 01:07:48,891 CARDIOVASCULAR DISEASE BUT THIS 1242 01:07:48,891 --> 01:07:51,093 MAY BE ANATOMIC AND MAY JUST BE 1243 01:07:51,093 --> 01:07:55,598 WOMEN HAVE A TENDENCY FOR MORE 1244 01:07:55,598 --> 01:07:57,767 DIFFUSED VOLUME ARE MORE 1245 01:07:57,767 --> 01:07:58,167 EXCESSIVE TISSUE. 1246 01:07:58,167 --> 01:08:03,606 >> CAN I MAKE A POINT ABOUT 1247 01:08:03,606 --> 01:08:03,806 THIS? 1248 01:08:03,806 --> 01:08:06,008 SO, DIPAN PRESENTED SOME DATA 1249 01:08:06,008 --> 01:08:08,244 ABOUT T1 MAPPING IN SEX 1250 01:08:08,244 --> 01:08:08,544 DIFFERENCES. 1251 01:08:08,544 --> 01:08:11,414 WHEN WE SEE CASES OF SUDDEN 1252 01:08:11,414 --> 01:08:13,382 CARDIAC ARREST IN FEMALES THAT 1253 01:08:13,382 --> 01:08:17,053 DON'T HAVE IT THE KEY POINT IS 1254 01:08:17,053 --> 01:08:21,123 REALLY THE DIFFUSED FIBROSIS, 1255 01:08:21,123 --> 01:08:24,327 THE INTERSTITIAL FIBROSIS FOR 1256 01:08:24,327 --> 01:08:29,332 NON DETECTION AND POSTMORTEM WE 1257 01:08:29,332 --> 01:08:31,934 HAVE SHOWN 30% OF CASES HAVE 1258 01:08:31,934 --> 01:08:34,403 REPLACEMENT FIBROSIS AND CASES 1259 01:08:34,403 --> 01:08:37,273 OF SUDDEN CARDIAC DEATH BUT ALL 1260 01:08:37,273 --> 01:08:38,174 HAVE INTERSTITIAL FIBROSIS. 1261 01:08:38,174 --> 01:08:40,409 THE KEY THING IS WE CAN'T 1262 01:08:40,409 --> 01:08:43,579 EXPLAIN CARDIAC ARREST BECAUSE 1263 01:08:43,579 --> 01:08:45,481 OF REPLACEMENT FIBROSIS. 1264 01:08:45,481 --> 01:08:49,285 WE HAVE TO THINK OF FIBROSIS AND 1265 01:08:49,285 --> 01:08:55,091 IT'S A PROBLEM WITH ANATOMY BUT 1266 01:08:55,091 --> 01:08:58,527 A MYOCARDIAL DIFFERENCE THAT MAY 1267 01:08:58,527 --> 01:09:01,864 BE HORMONAL OR GENETIC WE DON'T 1268 01:09:01,864 --> 01:09:05,868 KNOW BUT IN CASES WITHOUT SEVERE 1269 01:09:05,868 --> 01:09:08,504 CASES HAVE FIBROSIS UNRELATED TO 1270 01:09:08,504 --> 01:09:10,406 VOLUME AND MYOPATHIC PROCESS IN 1271 01:09:10,406 --> 01:09:13,676 FEMALES ESPECIALLY. 1272 01:09:13,676 --> 01:09:15,378 >> ONE POINT I'D LIKE TO MAKE IS 1273 01:09:15,378 --> 01:09:18,014 WE DIDN'T FIND IN OUR 1274 01:09:18,014 --> 01:09:18,948 ASSOCIATION BETWEEN THE PROLAPSE 1275 01:09:18,948 --> 01:09:26,055 AND ARRHYTHMIA WE DIDN'T FIND 1276 01:09:26,055 --> 01:09:36,399 RELATIONSHIP TO SEX. 1277 01:09:38,234 --> 01:09:48,678 THERE MAY BE A BIAS IN SAYING 1278 01:09:50,880 --> 01:09:54,216 WOMEN HAVE MORE ARRHYTHMIC RISK 1279 01:09:54,216 --> 01:09:56,118 AND IN THE NATURAL STUDIES THE 1280 01:09:56,118 --> 01:09:57,586 COHORT DON'T SHOW IT. 1281 01:09:57,586 --> 01:10:01,791 YOU SEE THE RISK WITH MR BUT NOT 1282 01:10:01,791 --> 01:10:07,596 WITH MORTALITY SO THE QUESTION 1283 01:10:07,596 --> 01:10:10,833 OF ARRHYTHMIA AND SEX REMAINS 1284 01:10:10,833 --> 01:10:15,037 QUITE NOT DEFINED AND I'M QUITE 1285 01:10:15,037 --> 01:10:19,175 RESISTANT TO SAY, OH, WOMEN HAVE 1286 01:10:19,175 --> 01:10:22,345 ARIDRHYTHMIA AND THERE'S THEIR 1287 01:10:22,345 --> 01:10:22,745 PROBLEM. 1288 01:10:22,745 --> 01:10:24,146 >> IT'S A QUESTION OF SETTING 1289 01:10:24,146 --> 01:10:27,583 AND LOOK AT THE POPULATION BUT 1290 01:10:27,583 --> 01:10:30,986 NOT WITH MORE PENETRANT VARIANCE 1291 01:10:30,986 --> 01:10:34,390 IS WHERE YOU SEE THE FEMALE 1292 01:10:34,390 --> 01:10:35,925 PRODOMINANCE AND DESCRIBED IN 1293 01:10:35,925 --> 01:10:37,293 THE PAST LITERATURE. 1294 01:10:37,293 --> 01:10:40,096 FROM ALL THAT IS IN MINUTE 1295 01:10:40,096 --> 01:10:43,566 VOLUME OF DATA AND SO WHEN YOU 1296 01:10:43,566 --> 01:10:47,236 GET LARGE NUMBERS YOU DON'T SEE 1297 01:10:47,236 --> 01:10:50,906 THE ASSOCIATION IN WOMEN AND SO 1298 01:10:50,906 --> 01:10:55,044 MAYBE WE NEED TO HAVE WORK ON 1299 01:10:55,044 --> 01:10:55,878 MITRAL VALVE PROLAPSE UP WOMEN 1300 01:10:55,878 --> 01:10:57,913 TO SEE IF THERE'S SOMETHING 1301 01:10:57,913 --> 01:11:01,417 SPECIAL IN TERMS OF RISK OF 1302 01:11:01,417 --> 01:11:03,586 SUDDEN DEATH BEYOND THE UNDER 1303 01:11:03,586 --> 01:11:14,096 ESTIMATION OF MR WE HAVE SEEN. 1304 01:11:30,079 --> 01:11:32,548 >> WOMEN WERE LESS LIKELY TO TWO 1305 01:11:32,548 --> 01:11:35,584 ON TO GET MITRAL VALVE SURGERY 1306 01:11:35,584 --> 01:11:37,319 COMPARED TO MEN. 1307 01:11:37,319 --> 01:11:39,288 THERE'S STILL A LOT OF STUFF TO 1308 01:11:39,288 --> 01:11:41,190 SORT OUT AND LARGER SAMPLE SIZES 1309 01:11:41,190 --> 01:11:44,660 WILL HELP BUT I THINK IT'S ALSO 1310 01:11:44,660 --> 01:11:47,696 IMPORTANT TO HAVE A LARGE GROUP 1311 01:11:47,696 --> 01:11:50,266 OF INVESTIGATORS TO ADDRESS THE 1312 01:11:50,266 --> 01:11:50,533 QUESTIONS. 1313 01:11:50,533 --> 01:11:58,808 >> I TO THINK FRANCESSCA'S POINT 1314 01:11:58,808 --> 01:12:03,979 IN MITRAL CARDIAL RESPONSE AND 1315 01:12:03,979 --> 01:12:13,122 LOOKING AT STEN OVERSOSIS AND T 1316 01:12:13,122 --> 01:12:20,796 WERE DIFFERENCES AND THE REASON 1317 01:12:20,796 --> 01:12:21,530 FRANK GOT US TOGETHER. 1318 01:12:21,530 --> 01:12:28,404 >> WE HAVE A QUESTION FROM THE 1319 01:12:28,404 --> 01:12:31,173 VIDEOCAST FROM DR. VASSAN. 1320 01:12:31,173 --> 01:12:39,248 THANK YOU, DR. SHAH THERE'S AN 1321 01:12:39,248 --> 01:12:41,650 ASSOCIATION BUT COMPENSATORY 1322 01:12:41,650 --> 01:12:42,952 MECHANISMS PROTECT THE VALVE 1323 01:12:42,952 --> 01:12:43,586 RATHER THAN THE CAUSE OF 1324 01:12:43,586 --> 01:12:48,457 MORBIDITY? 1325 01:12:48,457 --> 01:12:50,459 >> I'M NOT SURE I UNDERSTAND THE 1326 01:12:50,459 --> 01:12:52,428 QUESTION PAUSE WE'RE TALKING 1327 01:12:52,428 --> 01:12:55,264 ABOUT ARRHYTHMIAS AND THEY COULD 1328 01:12:55,264 --> 01:12:56,298 BE COMPENSATORY? 1329 01:12:56,298 --> 01:13:03,572 >> COULD THE FIBROSIS BEING 1330 01:13:03,572 --> 01:13:13,816 COMPENSATORY. 1331 01:13:50,085 --> 01:13:51,453 IT WOULD BE INTERESTING TO SEE 1332 01:13:51,453 --> 01:13:55,124 IF FIBROSIS CAN BE AN CAUSE AND 1333 01:13:55,124 --> 01:13:56,926 EFFECT RELATIONSHIP BUT I DON'T 1334 01:13:56,926 --> 01:14:07,336 THINK IT'S COMPENSATORY. 1335 01:14:07,770 --> 01:14:08,871 >> THANK YOU. 1336 01:14:08,871 --> 01:14:10,239 AGAIN WE HAVE TIME AT THE END 1337 01:14:10,239 --> 01:14:12,608 FOR DISCUSSION. 1338 01:14:12,608 --> 01:14:22,217 THE NEXT SPEAKER IS DR. MARIA 1339 01:14:22,217 --> 01:14:24,286 TRIVIERI FROM MOUNT SINAI. 1340 01:14:24,286 --> 01:14:28,490 SFWR IT'S A PLEASURE TO BE HERE 1341 01:14:28,490 --> 01:14:33,562 TODAY AND WANTED TO THANK DR 1342 01:14:33,562 --> 01:14:37,266 DR. EVANS FOR COMPOSING THE 1343 01:14:37,266 --> 01:14:39,201 SYMPOSIUM AND THE MEMBERS OF 1344 01:14:39,201 --> 01:14:39,602 NIH. 1345 01:14:39,602 --> 01:14:42,304 THE OBJECT OF MY TALK IS TO GO 1346 01:14:42,304 --> 01:14:44,840 OVER THE USE OF IMAGING IN 1347 01:14:44,840 --> 01:14:45,307 MITRAL VALVE PROLAPSE. 1348 01:14:45,307 --> 01:14:47,910 I'M ASSOCIATE PROFESSOR OF 1349 01:14:47,910 --> 01:14:50,813 CARDIOLOGY AT RADIOLOGY AT THE 1350 01:14:50,813 --> 01:14:53,415 ICAHN SCHOOL OF MEDICINE. 1351 01:14:53,415 --> 01:14:54,950 AND MY ONLY RELEVANT DISCLOSURE 1352 01:14:54,950 --> 01:14:57,286 ABOUT THE TALK IS I'M THE 1353 01:14:57,286 --> 01:14:59,054 CONTACT P.I. FOR A LARGE NIH 1354 01:14:59,054 --> 01:15:08,230 GRANT LOOKING AT THE USE OF 1355 01:15:08,230 --> 01:15:10,165 PET/MR IMAGING AND DR. MILLER 1356 01:15:10,165 --> 01:15:18,407 WILL BE SPEAKING AS WELL. 1357 01:15:18,407 --> 01:15:22,111 SO BRIEFLY MY OBJECTIVE WILL BE 1358 01:15:22,111 --> 01:15:25,314 TO REVIEW THE RATIONALE FOR THE 1359 01:15:25,314 --> 01:15:26,415 STUDY. 1360 01:15:26,415 --> 01:15:29,451 PROVIDE YOU WITH SOME EARLY 1361 01:15:29,451 --> 01:15:31,453 EVIDENCE OVER THE LAST FEW YEARS 1362 01:15:31,453 --> 01:15:35,157 ON THE USE OF THIS TECHNOLOGY IN 1363 01:15:35,157 --> 01:15:38,560 MITRAL VALVE PROLAPSE DISEASE 1364 01:15:38,560 --> 01:15:42,131 AND TOUCH UPON ONE OF THE NEW 1365 01:15:42,131 --> 01:15:44,600 TRACER INTRODUCED TO LOOK AT 1366 01:15:44,600 --> 01:15:54,977 MITRAL VALVE PROLAPSE. 1367 01:16:02,117 --> 01:16:05,154 IT SEEMS LIKE SOMEBODY'S NOT 1368 01:16:05,154 --> 01:16:08,857 ABLE TO SEE THE SLIDES. 1369 01:16:08,857 --> 01:16:11,960 IS THAT TRUE? 1370 01:16:11,960 --> 01:16:14,530 WHY HAVE WE BEEN THINKING OF 1371 01:16:14,530 --> 01:16:19,568 USING THE TECHNOLOGY AND PET 1372 01:16:19,568 --> 01:16:30,079 STANDS FOR POSITRON ELECTRIC 1373 01:16:32,748 --> 01:16:37,453 TOMOGRAPHY AND IT'S A HYBRID 1374 01:16:37,453 --> 01:16:39,588 TECHNIQUE OF THIS DATA AND MRI 1375 01:16:39,588 --> 01:16:49,698 DATA. 1376 01:16:57,940 --> 01:17:03,712 SO, AS WE HAVE HEARD OVER THE 1377 01:17:03,712 --> 01:17:10,786 PAST HOUR OR SO THE PATHOLOGY IS 1378 01:17:10,786 --> 01:17:12,654 IN MITRAL VALVE PROLAPSE DISEASE 1379 01:17:12,654 --> 01:17:17,593 THE SYSTOLIC MOTION OF THE 1380 01:17:17,593 --> 01:17:18,360 PERICPE 1381 01:17:18,360 --> 01:17:26,602 PERICARDIA IS THOUGHT TO EXERT 1382 01:17:26,602 --> 01:17:29,204 STRESS AND THERE BE CAUSE 1383 01:17:29,204 --> 01:17:33,408 MYOCARDIAL INJURY AND FIBROSIS. 1384 01:17:33,408 --> 01:17:35,911 DESPITE THIS HYPOTHESIS HAS BEEN 1385 01:17:35,911 --> 01:17:39,481 WIDELY ACCEPTED WE DON'T HAVE 1386 01:17:39,481 --> 01:17:41,650 MONITOR OR ACTIVE PATIENT 1387 01:17:41,650 --> 01:17:44,319 CHARACTERIZATION AND AS ALLUDED 1388 01:17:44,319 --> 01:17:47,589 TO BEFORE LG IS ASSOCIATED TO 1389 01:17:47,589 --> 01:17:49,358 WORSE PROGNOSIS BUT DON'T KNOW 1390 01:17:49,358 --> 01:17:54,396 IF A PERSON WITH IT WILL HAVE AN 1391 01:17:54,396 --> 01:17:54,596 EVENT. 1392 01:17:54,596 --> 01:17:56,665 AND THERE'S THE FEATURE THAT 1393 01:17:56,665 --> 01:17:58,500 PATIENTS ALLOW US TO ACCURATELY 1394 01:17:58,500 --> 01:17:59,701 CHARACTERIZE AND DECIDE ON 1395 01:17:59,701 --> 01:17:59,968 TREATMENT. 1396 01:17:59,968 --> 01:18:02,237 WE ALSO DON'T HAVE ACCEPTED 1397 01:18:02,237 --> 01:18:04,606 STRATEGY TO MANAGE AND REDUCE 1398 01:18:04,606 --> 01:18:09,478 THIS RISK AND THE IMPACT OF 1399 01:18:09,478 --> 01:18:15,050 MITRAL VALVE SURGERY ON 1400 01:18:15,050 --> 01:18:15,617 VENTRICULAR ARRHYTHMIAS IS 1401 01:18:15,617 --> 01:18:25,761 UNKNOWN. 1402 01:18:46,081 --> 01:18:47,583 WE CAN IDENTIFY WHAT CORRELATES 1403 01:18:47,583 --> 01:18:50,285 WITH THE RISK BUT LACK THE 1404 01:18:50,285 --> 01:18:55,591 ABILITY TO IDENTIFY SPECIFIC LEC 1405 01:18:55,591 --> 01:18:59,228 LAR PATHWAY AND HAVE THE ISSUE 1406 01:18:59,228 --> 01:19:00,996 WITH THE TEF MISSION AND THIS IS 1407 01:19:00,996 --> 01:19:04,533 CAR BUT WE CANNOT DISTINGUISH 1408 01:19:04,533 --> 01:19:07,236 ONE PATIENT FROM SCAR FROM 1409 01:19:07,236 --> 01:19:08,370 ANOTHER. 1410 01:19:08,370 --> 01:19:11,406 WITH AND WITHOUT ECHO WE CAN 1411 01:19:11,406 --> 01:19:13,842 GAIN MORPHOLOGY AND FUNCTION AND 1412 01:19:13,842 --> 01:19:15,744 DO LACK MOLECULAR DEFINITION. 1413 01:19:15,744 --> 01:19:17,346 ANOTHER IMAGING FEATURE TALKED 1414 01:19:17,346 --> 01:19:27,890 ABOUT THAT CAN BE SEEN WITH THIS 1415 01:19:29,057 --> 01:19:30,759 IS IS THE DYSFUNCTION AND SOME 1416 01:19:30,759 --> 01:19:33,829 THINK OF IT AS A NORMAL VARIANT. 1417 01:19:33,829 --> 01:19:38,433 WE STILL HAVE UNCERTAINTY 1418 01:19:38,433 --> 01:19:44,840 BETWEEN THE ARRHYTHMIA AND THE 1419 01:19:44,840 --> 01:19:55,284 REMODELLING AND DISJUNCTION. 1420 01:19:55,284 --> 01:19:59,588 SO WHAT DO WE THINK ABOUT USING 1421 01:19:59,588 --> 01:20:03,025 PET MRI IN MITRAL VALVE 1422 01:20:03,025 --> 01:20:03,292 PROLAPSE? 1423 01:20:03,292 --> 01:20:06,261 ONE REASON WE DECIDED TO USE THE 1424 01:20:06,261 --> 01:20:09,531 TECHNOLOGY WE'RE A REFERENCE 1425 01:20:09,531 --> 01:20:20,075 CENTER FOR CARDIAC SARCOIDOSIS 1426 01:20:24,579 --> 01:20:26,548 AND DID WORK IN PATIENTS AND 1427 01:20:26,548 --> 01:20:32,354 ABLE TO IDENTIFY SOME IMAGING 1428 01:20:32,354 --> 01:20:35,123 FEATURE THAT IN CARDIAC 1429 01:20:35,123 --> 01:20:36,658 SARCOIDOSIS PARTICIPANTS AND IN 1430 01:20:36,658 --> 01:20:38,660 THE SLIDES I WANTED TO PRESENT 1431 01:20:38,660 --> 01:20:41,964 IMAGES OF A PATIENT WITH CARDIAC 1432 01:20:41,964 --> 01:20:47,569 SARCOIDOSIS AND SEE ON THE FAR 1433 01:20:47,569 --> 01:20:53,608 LEFT AN IMAGE AND SEE THE 1434 01:20:53,608 --> 01:20:55,577 INSERTION POINT OF THE LEFT 1435 01:20:55,577 --> 01:20:58,013 VENTRICLE AND LOOKING AT THE EMR 1436 01:20:58,013 --> 01:20:59,247 YOU'RE NOT ABLE TO KNOW WHEN THE 1437 01:20:59,247 --> 01:21:00,482 PATIENTS ARE ACTIVE. 1438 01:21:00,482 --> 01:21:05,020 YOU CAN ONLY SEE SCAR. 1439 01:21:05,020 --> 01:21:07,856 IF YOU SUPER IMPOSE THE PET OVER 1440 01:21:07,856 --> 01:21:09,458 EMR YOU'LL SEE THE PATIENTS NOT 1441 01:21:09,458 --> 01:21:12,327 ONLY WITH SR BUT ACTIVE AND THAT 1442 01:21:12,327 --> 01:21:16,598 IS VERY IMPORTANT IN TERMS 1443 01:21:16,598 --> 01:21:18,000 DECIDING TREATMENT. 1444 01:21:18,000 --> 01:21:20,702 INTERESTINGLY THE DEFINITION WE 1445 01:21:20,702 --> 01:21:23,238 GET ON PET MR CORRELATES WELL 1446 01:21:23,238 --> 01:21:29,077 WITH THE HISTOLOGY AND JUST AS 1447 01:21:29,077 --> 01:21:31,947 AN EXAMPLE OF THE ACCURACY AND 1448 01:21:31,947 --> 01:21:38,687 WANTED TO SHOW THE PHASE OF THE 1449 01:21:38,687 --> 01:21:43,091 WITH THIS CARDIAC SARCOIDOSIS 1450 01:21:43,091 --> 01:21:45,093 AND SAW EVIDENCE OF SCAR WITH 1451 01:21:45,093 --> 01:21:51,566 ASSOCIATED UPTAKE OF FDG IN THE 1452 01:21:51,566 --> 01:21:53,301 SAME LOCATION. 1453 01:21:53,301 --> 01:21:58,407 WE'RE LOOKING AT THE MODALITY IN 1454 01:21:58,407 --> 01:22:06,548 CARDIAC SARCOIDOSIS WE FELT IT 1455 01:22:06,548 --> 01:22:07,582 LED TO INFORMATION FOR THE 1456 01:22:07,582 --> 01:22:16,091 MODALITY OF THE PRODUCTS. 1457 01:22:16,091 --> 01:22:17,826 AND IN THE LITERATURE IN CARDIAC 1458 01:22:17,826 --> 01:22:20,028 SARCOIDOSIS IS RELEVANT TO 1459 01:22:20,028 --> 01:22:21,863 MITRAL VALVE PROLAPSE BECAUSE 1460 01:22:21,863 --> 01:22:23,298 IT'S ASSOCIATED WITH ARRHYTHMIA 1461 01:22:23,298 --> 01:22:27,169 AND THERE'S EVIDENCE FROM THE 1462 01:22:27,169 --> 01:22:29,504 CLINICAL LITERATURE THAT 1463 01:22:29,504 --> 01:22:30,839 INFLAMMATION COULD BE IMPORTANT 1464 01:22:30,839 --> 01:22:32,841 IN MITRAL VALVE DISEASE. 1465 01:22:32,841 --> 01:22:36,378 THERE'S PRECLINICAL MODEL OF 1466 01:22:36,378 --> 01:22:37,979 MITRAL VALVE DISEASE IN THE 1467 01:22:37,979 --> 01:22:42,217 SYNDROME AND THE MODEL OF MITRAL 1468 01:22:42,217 --> 01:22:46,788 VALVE DISEASE WHAT INVESTIGATORS 1469 01:22:46,788 --> 01:22:50,525 FOUND WAS MIGHT INCREASE 1470 01:22:50,525 --> 01:22:52,594 MACROPHAGES WITH INCREASED CH 1471 01:22:52,594 --> 01:22:58,967 CHEMOKINE AND THE EXTRA CELLULAR 1472 01:22:58,967 --> 01:23:01,970 MATRIX IN AN INFLAMMATORY WAY 1473 01:23:01,970 --> 01:23:04,239 AND WHEN THEY INDUCED DEFICIENCY 1474 01:23:04,239 --> 01:23:06,141 OF MONOCYTE THEY ARE FOUND THAT 1475 01:23:06,141 --> 01:23:08,510 WAS PROTECTIVE AGAINST THE 1476 01:23:08,510 --> 01:23:13,615 DEVELOPMENT OF MITRAL VALVE 1477 01:23:13,615 --> 01:23:19,588 DISEASE AND REDUCTION IN LEAFLET 1478 01:23:19,588 --> 01:23:20,956 THICKENING PRESERVING THE 1479 01:23:20,956 --> 01:23:25,193 INTEGRITY AND DESPITE THE FACT 1480 01:23:25,193 --> 01:23:25,827 OF MITRAL VALVE DISEASE THERE 1481 01:23:25,827 --> 01:23:33,635 WAS NO FORMATION. 1482 01:23:33,635 --> 01:23:39,107 AND THERE'S AN EVIDENCE FROM THE 1483 01:23:39,107 --> 01:23:41,343 CLINICAL LITERATURE MUCH 1484 01:23:41,343 --> 01:23:42,310 INFLAMMATION BEING ASSOCIATED 1485 01:23:42,310 --> 01:23:45,113 WITH ROW LAPSE AND THEY CREATED 1486 01:23:45,113 --> 01:23:48,550 A GENETICALLY MODIFIED MOUSE 1487 01:23:48,550 --> 01:23:52,087 WHERE THEY SAW IN THE 1488 01:23:52,087 --> 01:23:54,756 INTRALATERAL WALL THERE WAS 1489 01:23:54,756 --> 01:24:03,265 INCREASED FIBROSIS AND 1490 01:24:03,265 --> 01:24:04,599 MACROPHAGE INCREASE AND SHOWING 1491 01:24:04,599 --> 01:24:15,143 A MARKER OF DISEASE PROGRESSION. 1492 01:24:22,484 --> 01:24:27,189 AND THE MODEL COULD BE PART OF 1493 01:24:27,189 --> 01:24:29,457 THE DISEASE PROCESS OF MITRAL 1494 01:24:29,457 --> 01:24:33,929 VALVE PROLAPSE AND MITRAL VALVE 1495 01:24:33,929 --> 01:24:35,830 DISEASE AND EXPLAIN THE 1496 01:24:35,830 --> 01:24:38,066 PROGRESSION OF FIBROSIS ARE IN 1497 01:24:38,066 --> 01:24:39,467 PATIENTS THAT LATER DEVELOPED 1498 01:24:39,467 --> 01:24:40,368 ENHANCEMENT. 1499 01:24:40,368 --> 01:24:44,039 ALL THE PRESENCE OF THE 1500 01:24:44,039 --> 01:24:47,809 VENTRICULAR ATROPHY FROM THE 1501 01:24:47,809 --> 01:24:49,544 BURDEN OF FIBROSIS AND EXPLAIN 1502 01:24:49,544 --> 01:24:53,215 WHY MAYBE PATIENTS WITH NO 1503 01:24:53,215 --> 01:24:59,621 FIBROSIS OR MINIMAL FIBROSIS CAN 1504 01:24:59,621 --> 01:25:01,690 EXPERIENCE THIS AND IN THE PRIOR 1505 01:25:01,690 --> 01:25:10,131 DISCUSSION. 1506 01:25:10,131 --> 01:25:12,834 WE ARE LEADING HYPOTHESIS THAT 1507 01:25:12,834 --> 01:25:14,803 INFLAMMATION IS A PART OF THE 1508 01:25:14,803 --> 01:25:16,304 PROLAPSE DISEASE EITHER IN THE 1509 01:25:16,304 --> 01:25:20,242 DEVELOPMENT OF FIBROSIS AS A 1510 01:25:20,242 --> 01:25:22,310 SUBSTRATE OR INCREASED 1511 01:25:22,310 --> 01:25:29,417 PHENOMENA. 1512 01:25:29,417 --> 01:25:31,653 SO WHEN WE STARTED LOOKING AT 1513 01:25:31,653 --> 01:25:36,591 THE USE OF THIS MODALITY WE WERE 1514 01:25:36,591 --> 01:25:42,130 THE FIRST TO USE PET/MR IN 1515 01:25:42,130 --> 01:25:42,731 MITRAL VALVE DISEASE AND THE 1516 01:25:42,731 --> 01:25:46,001 DATA WASN'T PUBLISHED SO WE 1517 01:25:46,001 --> 01:25:47,569 CONDUCTED THE PILOT STUDY WHICH 1518 01:25:47,569 --> 01:25:51,339 WAS FUNDAMENTAL IN GETTING OUR 1519 01:25:51,339 --> 01:25:54,309 WORK MOVING FAST AND THEN GET 1520 01:25:54,309 --> 01:25:56,478 THE SUBSEQUENT NIH AWARD WHERE 1521 01:25:56,478 --> 01:26:03,585 WE LOOKED AT THE PATIENT WITH 1522 01:26:03,585 --> 01:26:05,186 SEVERE MITRAL VALVE PROLAPSE AND 1523 01:26:05,186 --> 01:26:09,357 WE SAW IN 85% THERE WAS EVIDENCE 1524 01:26:09,357 --> 01:26:15,630 OF INCREASED UPTAKE IN THE BASAL 1525 01:26:15,630 --> 01:26:19,567 INTRALATERAL WALL AND 70% OF 1526 01:26:19,567 --> 01:26:24,272 PATIENTS SIMULTANEOUSLY HAD 1527 01:26:24,272 --> 01:26:25,473 POSITIVITY SHOWING INCREASE. 1528 01:26:25,473 --> 01:26:26,641 AND WHEN WE GROUP PATIENTS BASED 1529 01:26:26,641 --> 01:26:30,679 ON WHETHER OR NOT THEY HAVE 1530 01:26:30,679 --> 01:26:34,649 COMPLEX ARRHYTHMIA WE SAW 1531 01:26:34,649 --> 01:26:39,587 PATIENTS WITH COMPLEX 1532 01:26:39,587 --> 01:26:40,422 VENTRICULAR ARRHYTHMIA THEY ARE 1533 01:26:40,422 --> 01:26:43,258 HAD LATE ANNOUNCEMENT COMPARED 1534 01:26:43,258 --> 01:26:48,997 AND THE OPPOSITE FOR VENTRICULAR 1535 01:26:48,997 --> 01:26:51,499 AND THOSE WHO HAD MORE UPTAKE. 1536 01:26:51,499 --> 01:26:55,937 WHAT WE DID FEEL WAS WE ONLY HAD 1537 01:26:55,937 --> 01:26:58,206 20 PATIENTS AND COULDN'T 1538 01:26:58,206 --> 01:26:59,974 CONCLUDE ANYTHING DEFINITIVE BUT 1539 01:26:59,974 --> 01:27:10,518 OUR SPECULATION WAS LG AND FDG 1540 01:27:10,719 --> 01:27:21,129 PROPERTIED DIFFERENT STAGES. 1541 01:27:22,197 --> 01:27:27,535 THE FIRST PILOT STUDY LOOKED AT 1542 01:27:27,535 --> 01:27:29,204 PATIENTS WITH SEVERE 1543 01:27:29,204 --> 01:27:29,537 REGURGITATION. 1544 01:27:29,537 --> 01:27:31,573 WE WENT AHEAD AND STARTED 1545 01:27:31,573 --> 01:27:34,509 LOOKING AT PATIENTS WITH LESS 1546 01:27:34,509 --> 01:27:37,712 THAN SEVERE MR TO TRY TO 1547 01:27:37,712 --> 01:27:38,480 UNDERSTAND WHERE THERE COULD BE 1548 01:27:38,480 --> 01:27:41,716 PRESENCE OF UPTAKE IN PRESENCE 1549 01:27:41,716 --> 01:27:43,718 WITH LEAVE SEVERE MR. 1550 01:27:43,718 --> 01:27:49,357 THIS WAS APILOT STUDY OF LOOKING 1551 01:27:49,357 --> 01:27:52,293 AT APPROXIMATELY 12 PATIENTS AND 1552 01:27:52,293 --> 01:27:56,831 IN PATIENT WITH MILD TO MODERATE 1553 01:27:56,831 --> 01:28:01,870 MR WITH A HISTORY OF ATROPHY 1554 01:28:01,870 --> 01:28:05,774 THERE WAS A HIGH DEGREE OF FDG 1555 01:28:05,774 --> 01:28:09,411 POSITIVELY AND LGE POSITIVITY 1556 01:28:09,411 --> 01:28:11,346 WITH CONCORDANCE BETWEEN 1557 01:28:11,346 --> 01:28:13,047 INFLAMMATION AND SCAR UP TO 83% 1558 01:28:13,047 --> 01:28:19,387 WERE POSITIVE AND 75% OF THEM 1559 01:28:19,387 --> 01:28:27,962 POSITIVE ON FDG AND MR. 1560 01:28:27,962 --> 01:28:31,566 SO SOME OF YOU THAT MAY BE 1561 01:28:31,566 --> 01:28:35,470 FAMILIAR IF YOU CAN SCROLL 1562 01:28:35,470 --> 01:28:40,842 THROUGH MIGHT KNOWING TO A SCAN 1563 01:28:40,842 --> 01:28:44,045 WITH FDG COULD BE SOMETIMES 1564 01:28:44,045 --> 01:28:44,913 PROBLEMATIC. 1565 01:28:44,913 --> 01:28:48,016 WE HAVE TO ESSENTIALLY SWITCH 1566 01:28:48,016 --> 01:28:57,692 THE METABOLISM OF THE MYOCYTE 1567 01:28:57,692 --> 01:28:59,561 AND SOMETIMES CANNOT BE 1568 01:28:59,561 --> 01:29:03,164 ACHIEVED. 1569 01:29:03,164 --> 01:29:09,037 WE HAVE A SITUATION OF 1570 01:29:09,037 --> 01:29:11,573 SUPPRESSION AND A PATIENT NEEDS 1571 01:29:11,573 --> 01:29:15,009 TO FOLLOW A SPECIFIC TIGHT. 1572 01:29:15,009 --> 01:29:16,945 AS A RESULT OF THAT CAN LEAD TO 1573 01:29:16,945 --> 01:29:17,645 THIS RESULT. 1574 01:29:17,645 --> 01:29:19,380 TO COUNTER ACT THAT WE LOOKED AT 1575 01:29:19,380 --> 01:29:25,887 THE POSSIBILITY OF USING OTHER 1576 01:29:25,887 --> 01:29:36,397 TRACER IN MITRAL VALVE STEEZ. 1577 01:29:41,636 --> 01:29:44,739 AND THIS STAT IN RECEPTOR BIND 1578 01:29:44,739 --> 01:29:48,309 TO THE INFLAMMATORY CELL. 1579 01:29:48,309 --> 01:29:52,647 BASED ON THE LITERATURE IN HUMAN 1580 01:29:52,647 --> 01:29:59,587 MOSTLY USED TO IDENTIFY A NEURAL 1581 01:29:59,587 --> 01:30:02,624 ENDOCRINE TUMOR AND CAN 1582 01:30:02,624 --> 01:30:09,497 VISUALIZE THE LYMPHOSITE THE -- 1583 01:30:09,497 --> 01:30:12,667 LYMPHOCYTE AND CAN BE USED AS A 1584 01:30:12,667 --> 01:30:14,869 SURROGATE MARKER FOR 1585 01:30:14,869 --> 01:30:15,203 INFLAMMATION. 1586 01:30:15,203 --> 01:30:22,010 THEY LOOKED AT THE GA INFORM 1587 01:30:22,010 --> 01:30:32,453 DOTATATE IN THE RAT MODEL. 1588 01:30:33,154 --> 01:30:37,926 AND LOOKED AT THE USE OF GA 1589 01:30:37,926 --> 01:30:39,427 DOTATATE IN PATIENT. 1590 01:30:39,427 --> 01:30:40,895 THIS IS AN EXAMPLE OF HOW 1591 01:30:40,895 --> 01:30:43,565 POWERFUL THE TECHNIQUE CAN BE IN 1592 01:30:43,565 --> 01:30:45,300 IDENTIFIED DYNAMIC CHANGES 1593 01:30:45,300 --> 01:30:51,005 OCCURRING WITHIN THE MYOCARDIUM. 1594 01:30:51,005 --> 01:30:58,646 AND I THINK IT'S RELEVANT TO 1595 01:30:58,646 --> 01:31:05,486 SHOW HOW PET MRI TAKES PLACE AND 1596 01:31:05,486 --> 01:31:08,456 THIS IS 13 YEARS POST TRANSPLANT 1597 01:31:08,456 --> 01:31:10,692 ADMITTED FOR FAILURE AND TREATED 1598 01:31:10,692 --> 01:31:12,894 FOR REJECTION AND COMPLETED THE 1599 01:31:12,894 --> 01:31:14,662 TREATMENT FOR REJECTION AND 1600 01:31:14,662 --> 01:31:18,132 UNDERWENT A BIOPSY NEGATIVE AND 1601 01:31:18,132 --> 01:31:21,903 AT BASELINE GA DOTATATE SCAN AND 1602 01:31:21,903 --> 01:31:23,871 SEE IN THE SCAN THERE WAS NO 1603 01:31:23,871 --> 01:31:26,441 UPTAKE OF THE TRACER IN THE 1604 01:31:26,441 --> 01:31:28,142 PERICARDIUM AND SIX WEEKS LATER 1605 01:31:28,142 --> 01:31:33,214 THE PATIENT PRESENTED WITH 1606 01:31:33,214 --> 01:31:36,651 RECURRENT HEART FAILURE AND 1607 01:31:36,651 --> 01:31:38,252 UNDER GOES A SUBSEQUENT PET/MR 1608 01:31:38,252 --> 01:31:40,021 AND WERE ABLE TO SEE INCREASED 1609 01:31:40,021 --> 01:31:50,498 UPTAKE IN THE LATERAL WALL. 1610 01:31:53,501 --> 01:31:55,203 WHAT WAS INTERESTING IS WITH THE 1611 01:31:55,203 --> 01:31:57,605 TRACER WE WITH WERE ABLE TO 1612 01:31:57,605 --> 01:32:02,143 FOLLOW OVER TIME THE DYNAMIC 1613 01:32:02,143 --> 01:32:05,246 CHANGES TAKING PLACE IN THE 1614 01:32:05,246 --> 01:32:07,415 MYOCARDIUM AND LOOK AT THE AREA 1615 01:32:07,415 --> 01:32:08,750 AFFECTED AND THERE WAS GOOD 1616 01:32:08,750 --> 01:32:11,586 CORRELATION AND IN FACT THE 1617 01:32:11,586 --> 01:32:14,856 PATIENT CONSISTENT ONE WILL THE 1618 01:32:14,856 --> 01:32:18,159 FACT OF UPTAKE DEVELOPED THE AV 1619 01:32:18,159 --> 01:32:18,359 BLOCK. 1620 01:32:18,359 --> 01:32:21,929 A VERY POWERFUL TECHNIQUE TO 1621 01:32:21,929 --> 01:32:24,999 LOOK AT INFLAMMATION OF THE 1622 01:32:24,999 --> 01:32:25,299 MYOCARDIUM. 1623 01:32:25,299 --> 01:32:27,869 AND RELEVANT TO MITRAL VALVE 1624 01:32:27,869 --> 01:32:30,571 PROLAPSE AND THE POSSIBILITY OF 1625 01:32:30,571 --> 01:32:31,205 SEEING EVOLUTION OF DISEASE OVER 1626 01:32:31,205 --> 01:32:41,315 TIME. 1627 01:32:41,516 --> 01:32:43,518 ON THE BASIS OF THE OBSERVATION 1628 01:32:43,518 --> 01:32:45,787 I MENTIONED WE THEN DESIGN THE 1629 01:32:45,787 --> 01:32:49,357 CLINICAL STUDY POSUPPORTED BY T 1630 01:32:49,357 --> 01:32:54,495 GRANT TO LOOK AT MITRAL VALVE 1631 01:32:54,495 --> 01:32:55,930 PROLAPSE WITH PET MRI. 1632 01:32:55,930 --> 01:32:59,133 WE HAVE A TWO COHORT AN ONE OF 1633 01:32:59,133 --> 01:33:02,036 THE SURGICAL CORD INCLUDES 1634 01:33:02,036 --> 01:33:03,171 PATIENTS WITH PLANNED REPAIR 1635 01:33:03,171 --> 01:33:08,009 SURGERY AS PART OF THE CLINICAL 1636 01:33:08,009 --> 01:33:12,647 INDICATION FOR MITRAL VALVE 1637 01:33:12,647 --> 01:33:12,914 PROLAPSE. 1638 01:33:12,914 --> 01:33:15,983 THE PATIENT WILL UNDER GO TWO 1639 01:33:15,983 --> 01:33:24,192 SCANS ONE WITH FDG AND ONE WITH 1640 01:33:24,192 --> 01:33:25,493 GA DOTATATE AND IDENTIFIED AS 1641 01:33:25,493 --> 01:33:33,134 MORE ACTIVE ON IMAGING. 1642 01:33:33,134 --> 01:33:35,803 AND THE ALL OF THIS PROPOSAL IS 1643 01:33:35,803 --> 01:33:39,574 ESSENTIALLY TO LOOK AT CHANGES 1644 01:33:39,574 --> 01:33:43,878 IN INFLAMMATION AS WELL AS 1645 01:33:43,878 --> 01:33:46,280 ARRHYTHMIA IN RESPONSE TO 1646 01:33:46,280 --> 01:33:49,817 SURGERY AND UNDER TWO A PET MR 1647 01:33:49,817 --> 01:33:52,186 IMAGING AT BASELINE AND AGAIN AT 1648 01:33:52,186 --> 01:34:02,697 24 MONTHS AFTER INITIAL SCAN. 1649 01:34:11,739 --> 01:34:15,743 THIS IS SHOWING THE WORK FLOW WE 1650 01:34:15,743 --> 01:34:20,248 FOLLOW AND THE SCAN AND PLANNED 1651 01:34:20,248 --> 01:34:22,216 THE BIOPSY ON THE BASIS OF THE 1652 01:34:22,216 --> 01:34:24,619 AREA WE SEE AND THEN ANALYZE THE 1653 01:34:24,619 --> 01:34:34,996 TISSUE WITH HISTOLOGY. 1654 01:34:40,902 --> 01:34:42,870 WHAT I WANTED TO ESSENTIALLY 1655 01:34:42,870 --> 01:34:46,607 PRESENT WAS THE USEFULNESS OF 1656 01:34:46,607 --> 01:34:50,912 THE TECHNIQUE IN THE CAMPUS OF 1657 01:34:50,912 --> 01:34:54,582 MITRAL VALVE DISEASE BECAUSE OF 1658 01:34:54,582 --> 01:34:58,686 THE LACK OF UNDERSTANDING OF THE 1659 01:34:58,686 --> 01:35:00,221 STRATIFICATION THAT CAN 1660 01:35:00,221 --> 01:35:01,422 CONTRIBUTE TO THE PHENOTYPE AND 1661 01:35:01,422 --> 01:35:04,292 WE HEARD ABOUT IMAGING MODALITY 1662 01:35:04,292 --> 01:35:10,565 AND PROVIDED INTO THE 1663 01:35:10,565 --> 01:35:11,866 PATHOPHYSIOLOGY OF DISEASE AND 1664 01:35:11,866 --> 01:35:14,602 LACK THE PROCESSES THAT OCCUR 1665 01:35:14,602 --> 01:35:21,309 WITH THE MYOCARDIUM AND BELIEVE 1666 01:35:21,309 --> 01:35:27,582 PET/MR CAN PROVIDE THAT AND IF 1667 01:35:27,582 --> 01:35:30,818 COUPLED WITH FDG AND GA DOTATATE 1668 01:35:30,818 --> 01:35:32,620 I THINK IT'S A PROMISING NEW 1669 01:35:32,620 --> 01:35:35,556 TOOL WHICH CAN BE USED TO 1670 01:35:35,556 --> 01:35:41,729 PREDICT IN PATIENTS WITH MITRAL 1671 01:35:41,729 --> 01:35:44,832 VALVE DISEASE AND STRATEGY FOR 1672 01:35:44,832 --> 01:35:46,133 MR AND ARRHYTHMIA PRESENTATION 1673 01:35:46,133 --> 01:35:46,968 AND THANK YOU FOR LISTENING AND 1674 01:35:46,968 --> 01:35:49,770 THAT WAS MY PRESENTATION. 1675 01:35:49,770 --> 01:35:55,910 >> THANK YOU VERY MUCH. 1676 01:35:55,910 --> 01:35:58,079 DOES ANYONE HAVE QUESTIONS OR 1677 01:35:58,079 --> 01:35:58,713 COMMENTS ABOUT THIS PARTICULAR 1678 01:35:58,713 --> 01:36:08,956 PRESENTATION? 1679 01:36:09,824 --> 01:36:14,262 >> WHAT I'VE BEEN STRUCK BY IS 1680 01:36:14,262 --> 01:36:18,733 SOME PATIENTS HAVE THEIR 1681 01:36:18,733 --> 01:36:21,068 ECHOCARDIOGRAM LOOKS GARDEN 1682 01:36:21,068 --> 01:36:22,670 VARIETY WITH PRESERVED LV 1683 01:36:22,670 --> 01:36:23,938 FUNCTION AND YET THEIR HEARTS 1684 01:36:23,938 --> 01:36:25,172 ARE BRIGHT RED WHEN YOU STUDY 1685 01:36:25,172 --> 01:36:35,283 THEM. 1686 01:36:49,864 --> 01:36:55,569 IT ALLOWS US TO SEE THINGS 1687 01:36:55,569 --> 01:37:06,280 EARLIER THAN OTHER ABNORMALITIES 1688 01:37:12,153 --> 01:37:18,826 AND WITH GA DOTATATE WE MAY HAVE 1689 01:37:18,826 --> 01:37:29,203 THE CONCENTRATION BY 1690 01:37:34,108 --> 01:37:35,109 INFLAMMATORY CELLS. 1691 01:37:35,109 --> 01:37:37,144 >> I WAS IN WASHINGTON AT A 1692 01:37:37,144 --> 01:37:39,880 MEETING PRESENTING THE OTHER DAY 1693 01:37:39,880 --> 01:37:43,284 AND WHEN I CAME OFF THE STAGE A 1694 01:37:43,284 --> 01:37:48,723 CARDIOLOGIST CAME TO ME WITH HIS 1695 01:37:48,723 --> 01:37:51,192 CD AND HIS SYSTOLIC DIMENSION IS 1696 01:37:51,192 --> 01:37:53,361 ABOUT 32 AND RUNNING MANY MILES 1697 01:37:53,361 --> 01:37:54,962 A WEEK WITHOUT ANY PROBLEMS AND 1698 01:37:54,962 --> 01:37:55,997 WANTED TO KNOW WHETHER TO HAVE 1699 01:37:55,997 --> 01:37:59,133 SURGERY OR NOT AND I TOLD HIM HE 1700 01:37:59,133 --> 01:38:01,836 SHOULD ENROLL IN THE TRIAL TO TO 1701 01:38:01,836 --> 01:38:04,705 THE PROPER ANALYSIS AT THE 1702 01:38:04,705 --> 01:38:07,575 MOLECULAR LEVEL BECAUSE IF HIS 1703 01:38:07,575 --> 01:38:09,010 HEART DOESN'T LIGHT UP IT'S OKAY 1704 01:38:09,010 --> 01:38:11,579 TO KEEP WAITING AND DO STRESS 1705 01:38:11,579 --> 01:38:14,815 ECHO IF IT LIT UP I ALWAYS SAID 1706 01:38:14,815 --> 01:38:16,717 THAT'S ANOTHER WAY TO ADD A NEW 1707 01:38:16,717 --> 01:38:22,690 LENS TO ACTIVE SURVEILLANCE FOR 1708 01:38:22,690 --> 01:38:25,259 PATIENTS AND I HAVE A HUNCH 1709 01:38:25,259 --> 01:38:27,228 THEY'LL BE PERSUADED BASED ON 1710 01:38:27,228 --> 01:38:29,530 THE IMAGING YOU'VE BEEN 1711 01:38:29,530 --> 01:38:37,238 PRESENTING. 1712 01:38:37,238 --> 01:38:38,039 >> THANK YOU. 1713 01:38:38,039 --> 01:38:41,542 IN THE 2021 MEETING WE USED A 1714 01:38:41,542 --> 01:38:43,244 SPEAKER AND DISCUSSANT FOR MAT. 1715 01:38:43,244 --> 01:38:44,912 WE HAVE BEEN TO AWAY FROM THAT 1716 01:38:44,912 --> 01:38:47,181 IN THE 2024 MEETING BUT IN THIS 1717 01:38:47,181 --> 01:38:52,420 MEETING WE HAVE A DISCUSSANT, 1718 01:38:52,420 --> 01:38:54,722 IT'S DR. JONATHAN WEINSAFT. 1719 01:38:54,722 --> 01:38:55,990 WOULD YOU LIKE TO LEAD THE 1720 01:38:55,990 --> 01:38:56,290 DISCUSSION? 1721 01:38:56,290 --> 01:39:01,562 >> THANK YOU, FRANK AND THANKS 1722 01:39:01,562 --> 01:39:04,398 WILL TO EVERYONE FOR PHENOMENAL 1723 01:39:04,398 --> 01:39:04,732 TALKS. 1724 01:39:04,732 --> 01:39:08,602 I'LL ASK A FEW BROAD QUESTIONS 1725 01:39:08,602 --> 01:39:13,174 AND THEN CERTAINLY OPEN THE 1726 01:39:13,174 --> 01:39:14,175 FLOOR FOR MANY IN THE AUDIENCE 1727 01:39:14,175 --> 01:39:24,718 WHO HAVE DONE WORK IN THIS AREA. 1728 01:39:27,621 --> 01:39:32,860 YOU'VE GIVEN DATA ON PET/MR 1729 01:39:32,860 --> 01:39:34,395 IMAGING AND WANT TO START WITH 1730 01:39:34,395 --> 01:39:35,763 YOU WHAT WE'RE FUNDAMENTALLY 1731 01:39:35,763 --> 01:39:38,432 MEASURING IN TERMS OF THE PET 1732 01:39:38,432 --> 01:39:39,033 DATA? 1733 01:39:39,033 --> 01:39:41,836 THE MEASURE IS A FUNDAMENTAL 1734 01:39:41,836 --> 01:39:52,379 MEASURE OF GLUCOSE UTILIZATION 1735 01:39:52,780 --> 01:40:03,257 AND COULD REPRESENT AN AND LOOK 1736 01:40:04,825 --> 01:40:15,169 AT CONTRACTILE DYNAMICS. 1737 01:40:22,776 --> 01:40:27,581 OR IS THE PREMISE THERE'S A 1738 01:40:27,581 --> 01:40:29,016 PRIMARY MOLECULAR INFLAMMATORY 1739 01:40:29,016 --> 01:40:30,084 PROCESS WHICH WOULD INFORM A 1740 01:40:30,084 --> 01:40:31,652 DIFFERENT AREA OF THERAPY? 1741 01:40:31,652 --> 01:40:42,163 >> THANK YOU FOR THE QUESTION. 1742 01:40:42,463 --> 01:40:49,737 WE HAVE MYOCYTES RAND ONE OF THE 1743 01:40:49,737 --> 01:40:51,372 REASONS WE DECIDED TO 1744 01:40:51,372 --> 01:40:54,575 INCORPORATE IN OUR STUDY A 1745 01:40:54,575 --> 01:40:55,409 TRACER MORE SPECIFIC FOR 1746 01:40:55,409 --> 01:40:57,044 INFLAMMATORY CELL AND I THINK BY 1747 01:40:57,044 --> 01:41:04,552 LOOKING AT THE COMPARISON OF THE 1748 01:41:04,552 --> 01:41:07,922 SCAN AND THE PATHOLOGY WE'LL BE 1749 01:41:07,922 --> 01:41:10,357 IN A POSITION TO UNDERSTAND WHAT 1750 01:41:10,357 --> 01:41:12,092 IS STRESS AND INFLAMMATION. 1751 01:41:12,092 --> 01:41:14,929 REGARDLESS OF WHETHER OR NOT IT 1752 01:41:14,929 --> 01:41:16,730 SHOWS INFLAMMATORY TRAITS 1753 01:41:16,730 --> 01:41:18,866 REGARDLESS OF THE NATURE OF THE 1754 01:41:18,866 --> 01:41:21,168 SIGNAL, THERE'S A SIGNAL WE CAN 1755 01:41:21,168 --> 01:41:24,705 STILL USE TO IDENTIFY AND 1756 01:41:24,705 --> 01:41:26,473 PROGNOSTICATE WITH THAT IS AN 1757 01:41:26,473 --> 01:41:31,212 ADDITIVE OR ADDITIONAL TO LG. 1758 01:41:31,212 --> 01:41:33,380 WHAT I'M TRYING TO SAY IS YOU 1759 01:41:33,380 --> 01:41:34,715 CAN LOOK AT THE SIGNAL AS A 1760 01:41:34,715 --> 01:41:36,283 STAND ALONE AND POSITIVE AND 1761 01:41:36,283 --> 01:41:37,351 NEGATIVE WHAT DOES THAT MEAN AND 1762 01:41:37,351 --> 01:41:40,521 LOOK AT THE SPECIFIC OF THE FDG 1763 01:41:40,521 --> 01:41:40,921 SIGNAL. 1764 01:41:40,921 --> 01:41:46,393 AND I THINK FOR THAT, WHAT I 1765 01:41:46,393 --> 01:41:51,498 FEEL WILL BE FUNDAMENTAL IS THE 1766 01:41:51,498 --> 01:41:53,200 SCAN. 1767 01:41:53,200 --> 01:41:59,740 AND WE CAN ALSO USE PRESENCE OF 1768 01:41:59,740 --> 01:42:02,776 FDG OR LGE AND REPRESENTATIVE 1769 01:42:02,776 --> 01:42:04,478 ISCHEMIA AS A MARKER OF RISK. 1770 01:42:04,478 --> 01:42:06,547 THERE'S A BROADER WAY OF LOOKING 1771 01:42:06,547 --> 01:42:12,820 AND MORE REFINED OR HISTOLOGICAL 1772 01:42:12,820 --> 01:42:13,487 WAY. 1773 01:42:13,487 --> 01:42:15,022 PRIOR TO OUR WORK THERE WAS NO 1774 01:42:15,022 --> 01:42:17,858 LITERATURE IN THE USE OF THIS 1775 01:42:17,858 --> 01:42:20,828 MODALITY SO I THINK WHAT OUR 1776 01:42:20,828 --> 01:42:22,129 LONGITUDINAL STUDY, PROSPECTIVE 1777 01:42:22,129 --> 01:42:24,965 STUDY IS GOING TO SHOW AND 1778 01:42:24,965 --> 01:42:28,736 PROVIDE US INFORMATION ON WHAT 1779 01:42:28,736 --> 01:42:30,738 EXACTLY THAT MEANS. 1780 01:42:30,738 --> 01:42:33,641 I THINK THE COMBINATION WITH THE 1781 01:42:33,641 --> 01:42:38,412 HISTOLOGY AS WELL AS THE SCAN 1782 01:42:38,412 --> 01:42:43,517 WE'LL BE DOING IN THE 1783 01:42:43,517 --> 01:42:45,085 NON-SURGICAL CAUSE CAN SHOW SOME 1784 01:42:45,085 --> 01:42:46,220 INFLAMMATION AND LOOK AT THIS AS 1785 01:42:46,220 --> 01:42:49,189 A MARKER REGARDLESS OF THE 1786 01:42:49,189 --> 01:42:49,623 UNDERLYING MATRIX. 1787 01:42:49,623 --> 01:42:51,558 I DON'T KNOW WHETHER THAT 1788 01:42:51,558 --> 01:42:55,562 ANSWERED YOUR QUESTION. 1789 01:42:55,562 --> 01:43:05,439 >> THAT'S IMPORTANT. 1790 01:43:05,439 --> 01:43:10,711 >> DR. HUNG AND TRIVIERI HAVE 1791 01:43:10,711 --> 01:43:14,748 OPPORTUNITY WORK AND IN TERMS OF 1792 01:43:14,748 --> 01:43:15,316 MITRAL VALVE PROLAPSE WITH 1793 01:43:15,316 --> 01:43:17,718 REGARD TO VENTRICULAR SUBSTRATE, 1794 01:43:17,718 --> 01:43:21,388 HOW DOES THAT IMPACT OUR 1795 01:43:21,388 --> 01:43:22,756 THINKING IN SURGICAL 1796 01:43:22,756 --> 01:43:26,193 INTERVENTIONS AND SHOULD THE 1797 01:43:26,193 --> 01:43:28,729 FINDING OF FIBROSIS OR SHOWING 1798 01:43:28,729 --> 01:43:33,334 THE ENHANCEMENTS ALTERED 1799 01:43:33,334 --> 01:43:36,570 MYOCARDIAL STRAIN BE USED TO 1800 01:43:36,570 --> 01:43:38,972 TIME THE CUTANEOUS INTERVENTIONS 1801 01:43:38,972 --> 01:43:40,841 AND IRRESPECTIVE OF THE TIMING 1802 01:43:40,841 --> 01:43:46,313 OF THE INTERVENTIONS, HOW TO WE 1803 01:43:46,313 --> 01:43:49,149 APPROACH THE PATIENT WHO'S BEEN 1804 01:43:49,149 --> 01:43:59,660 INTERVENED AND HAD THE MITRAL 1805 01:44:00,661 --> 01:44:01,695 REGURGITATION AFFECTED AND 1806 01:44:01,695 --> 01:44:03,063 REMAINS ALTERED. 1807 01:44:03,063 --> 01:44:05,032 >> I'LL START OFF. 1808 01:44:05,032 --> 01:44:06,467 YOU'RE VERY GOOD AT ASKING VERY 1809 01:44:06,467 --> 01:44:07,901 TOUGH QUESTIONS. 1810 01:44:07,901 --> 01:44:09,169 I AGREE 100%. 1811 01:44:09,169 --> 01:44:12,239 I DON'T KNOW WE HAVE ANY DATA 1812 01:44:12,239 --> 01:44:15,909 RIGHT NOW TO SAY OKAY BASED ON 1813 01:44:15,909 --> 01:44:18,846 THE PRESENCE OR EXTENT OF 1814 01:44:18,846 --> 01:44:20,347 FIBROSIS COULD THAT INFORM 1815 01:44:20,347 --> 01:44:21,315 DECISION FOR EARLIER 1816 01:44:21,315 --> 01:44:24,685 INTERVENTION IN A PATIENT WHO 1817 01:44:24,685 --> 01:44:28,389 OTHERWISE DOESN'T MEET THE 1818 01:44:28,389 --> 01:44:29,189 INTERVENTIONAL CRITERIA AND 1819 01:44:29,189 --> 01:44:29,523 APPROACH? 1820 01:44:29,523 --> 01:44:32,393 I DON'T THINK WE HAVE DATA ON 1821 01:44:32,393 --> 01:44:34,094 THAT RIGHT NOW SO IT'S A VERY 1822 01:44:34,094 --> 01:44:35,129 GOOD QUESTION. 1823 01:44:35,129 --> 01:44:37,464 THIS CONCEPT OF SAYING FIBROSIS 1824 01:44:37,464 --> 01:44:40,334 AS A MARKER AND THE HEALTH OF 1825 01:44:40,334 --> 01:44:43,337 THE VENTRICLE COULD THAT INFORM 1826 01:44:43,337 --> 01:44:45,339 EARLIER SURGERY AS BEING TESTED 1827 01:44:45,339 --> 01:44:49,476 IN OTHER -- BESIDES THE MITRAL 1828 01:44:49,476 --> 01:44:50,244 VALVE PROLAPSE. 1829 01:44:50,244 --> 01:44:51,412 I THINK THE QUESTION STILL 1830 01:44:51,412 --> 01:44:52,246 REMAINS TO BE ANSWERED. 1831 01:44:52,246 --> 01:44:55,716 I DON'T THINK WE KNOW THE ANSWER 1832 01:44:55,716 --> 01:45:06,059 TO THAT YET. 1833 01:45:06,059 --> 01:45:08,962 >> IF THEY FEEL THE VENTRICLE'S 1834 01:45:08,962 --> 01:45:10,998 SMALL AND ASKING ME I DOES THE 1835 01:45:10,998 --> 01:45:12,733 STRESS STUDY AND WENT 12 MINUTES 1836 01:45:12,733 --> 01:45:14,768 AND FEEL GREAT, DO I NEED 1837 01:45:14,768 --> 01:45:16,770 SURGERY OR CAN I WAIT SIX MONTHS 1838 01:45:16,770 --> 01:45:19,740 AND YOU DO THE MRI AND SHOW THEY 1839 01:45:19,740 --> 01:45:22,342 HAVE VENTRICLE WITH A LOT OF 1840 01:45:22,342 --> 01:45:23,677 SCAR IN IT ARE YOU GOING TO SAY 1841 01:45:23,677 --> 01:45:25,512 WE DON'T KNOW BECAUSE WE DON'T 1842 01:45:25,512 --> 01:45:29,683 HAVE THE RANDOMIZED TRIAL OR 1843 01:45:29,683 --> 01:45:30,484 LONGITUDINAL FOLLOW-UP AND A LOT 1844 01:45:30,484 --> 01:45:33,053 OF THE VALVE DECISIONS ARE STILL 1845 01:45:33,053 --> 01:45:34,621 MADE EVIDENCE OF C AND WHAT 1846 01:45:34,621 --> 01:45:36,290 WOULD YOU RECOMMEND TO THE 1847 01:45:36,290 --> 01:45:36,523 PATIENT? 1848 01:45:36,523 --> 01:45:40,327 >> YOU LIKE TO PIN PEOPLE DON'T, 1849 01:45:40,327 --> 01:45:41,128 DON'T CHA? 1850 01:45:41,128 --> 01:45:44,264 YOU BRING UP A GOOD POINT WHICH 1851 01:45:44,264 --> 01:45:45,999 IS IN CLINICAL PRACTICE YOU MAKE 1852 01:45:45,999 --> 01:45:48,669 DECISIONS IN THE ABSENCE OF 1853 01:45:48,669 --> 01:45:50,070 RANDOMIZED OR LONGITUDINAL 1854 01:45:50,070 --> 01:45:51,071 FOLLOW-UP DATA. 1855 01:45:51,071 --> 01:45:54,808 YES, I TAKE THAT AS ONE MARKER 1856 01:45:54,808 --> 01:45:56,977 TO SAY, HEY, THIS VENTRICLE FROM 1857 01:45:56,977 --> 01:45:59,213 THE STANDPOINT OF HOW IT'S 1858 01:45:59,213 --> 01:46:00,914 TOLERATING WHATEVER LOAD IT HAS 1859 01:46:00,914 --> 01:46:10,858 WHETHER MVP OR REGIRTHTATION -- 1860 01:46:10,858 --> 01:46:13,460 REGIRTHTATION AND 1861 01:46:27,708 --> 01:46:33,814 S AND ONE THING WE KNOW IS WITH 1862 01:46:33,814 --> 01:46:41,555 THE FIBROSIS WE SEE BY LGE IS 1863 01:46:41,555 --> 01:46:44,491 IRREVERSIBLE SUBSTRATE AND IT'S 1864 01:46:44,491 --> 01:46:45,592 A QUESTION TO TRY TO SORT OUT 1865 01:46:45,592 --> 01:46:46,960 FURTHER. 1866 01:46:46,960 --> 01:46:48,695 >> AND DAVID, LET ME COMMENT ON 1867 01:46:48,695 --> 01:46:52,099 THAT IN TERMS OF THINKING ABOUT 1868 01:46:52,099 --> 01:46:54,134 WITH RESPECT TO ENHANCEMENT AND 1869 01:46:54,134 --> 01:46:55,602 YOU CERTAINLY CAN COMMENT ON 1870 01:46:55,602 --> 01:46:57,237 THIS AS WELL. 1871 01:46:57,237 --> 01:47:02,042 THE OVERWHELMING BODY OF DATA WE 1872 01:47:02,042 --> 01:47:03,377 HAVE WITH RESPECT TO THE 1873 01:47:03,377 --> 01:47:07,080 ENHANCEMENT AND THE UTILITY AS A 1874 01:47:07,080 --> 01:47:09,449 PREDICTOR OF VENTRICULAR 1875 01:47:09,449 --> 01:47:15,055 REMODELLING IN SURGERY RELATES 1876 01:47:15,055 --> 01:47:18,425 TO PATIENTS ONE ISCHEMIC 1877 01:47:18,425 --> 01:47:20,994 MYOPATHY WHICH IS A HIGHLY 1878 01:47:20,994 --> 01:47:23,297 POWERFUL PREDICTOR OF MARKER OF 1879 01:47:23,297 --> 01:47:26,900 IMPROVED REMODELLING IN SURGICAL 1880 01:47:26,900 --> 01:47:28,769 OR CUTANEOUS INTERVENTIONS. 1881 01:47:28,769 --> 01:47:31,605 IN PATIENTS WITH PROLAPSE WE'RE 1882 01:47:31,605 --> 01:47:34,274 TYPICALLY TALKING ABOUT 1883 01:47:34,274 --> 01:47:36,910 MYOCARDIAL FIBROSIS AND 2% TO 5% 1884 01:47:36,910 --> 01:47:44,685 OF LEFT VENTRICULAR MYOCARDIUM. 1885 01:47:44,685 --> 01:47:48,455 I ASK THE QUESTION BACK TO DIPAN 1886 01:47:48,455 --> 01:47:54,127 OR TO YOU, DAVID OR OTHERS, DO 1887 01:47:54,127 --> 01:47:56,897 WE HAVE DATA DEMONSTRATING THE 1888 01:47:56,897 --> 01:47:59,566 ENHANCEMENT IS A PREDICTOR OF 1889 01:47:59,566 --> 01:48:02,636 ADVERSE REMODELLING AFTER 1890 01:48:02,636 --> 01:48:04,571 SURGICAL OR CUTANEOUS VALVE 1891 01:48:04,571 --> 01:48:04,805 REPAIR? 1892 01:48:04,805 --> 01:48:07,040 ARE THESE THE PATIENT FALL OFF 1893 01:48:07,040 --> 01:48:07,841 THE CLIFF? 1894 01:48:07,841 --> 01:48:10,544 >> WE DON'T KNOW THAT YET BUT I 1895 01:48:10,544 --> 01:48:11,211 THINK THIS IS INTERESTING BEEN 1896 01:48:11,211 --> 01:48:13,747 BECAUSE WE HAVE THE VOLUME I'LL 1897 01:48:13,747 --> 01:48:16,516 TALK ABOUT TOMORROW ABOUT 1898 01:48:16,516 --> 01:48:16,750 SURGERY. 1899 01:48:16,750 --> 01:48:18,585 THE VOLUME LOAD FROM 1900 01:48:18,585 --> 01:48:21,555 REGURGITATION AND ALSO HAVE THE 1901 01:48:21,555 --> 01:48:22,990 POTENTIAL FOR TENSION WHETHER 1902 01:48:22,990 --> 01:48:25,525 THAT'S CREATING ISCHEMIA OR WHAT 1903 01:48:25,525 --> 01:48:28,762 THE TENSION OF THESE LARGE 1904 01:48:28,762 --> 01:48:37,604 LEAFLETS IS DOING ASYSTOLE 1905 01:48:37,604 --> 01:48:39,006 TUGGING ON THE MUSCLE AND 1906 01:48:39,006 --> 01:48:41,708 DIFFERENT FROM ISCHEMIC DISEASE. 1907 01:48:41,708 --> 01:48:44,444 ON THE OTHER HAND I'M SURE MARK 1908 01:48:44,444 --> 01:48:46,113 WILL HAVE A COMMENT AND WHAT I 1909 01:48:46,113 --> 01:48:48,348 DON'T WANT TO HAVE IS SCAR THAT 1910 01:48:48,348 --> 01:48:50,283 THEN RELATES TO ARRHYTHMIAS 1911 01:48:50,283 --> 01:48:51,418 BECAUSE THE WAY WE LOSE THE GAME 1912 01:48:51,418 --> 01:49:00,794 THESE DAYS IS TO HAVE MALIGNANT 1913 01:49:00,794 --> 01:49:01,128 ARRHYTHMIA. 1914 01:49:01,128 --> 01:49:03,530 I THINK THAT'S THE SUDDEN DEATH 1915 01:49:03,530 --> 01:49:06,166 RISK WE'VE SEEN THE LAST 45 1916 01:49:06,166 --> 01:49:07,601 YEARS AND I NEVER REALLY 1917 01:49:07,601 --> 01:49:09,870 UNDERSTOOD IT UNTIL A FEW YEARS 1918 01:49:09,870 --> 01:49:12,472 AGO, THANK YOU, CONGRESSMAN BARR 1919 01:49:12,472 --> 01:49:13,306 AND OTHERS FOR GETTING US 1920 01:49:13,306 --> 01:49:14,708 PLUGGED INTO THIS AND THE WORK 1921 01:49:14,708 --> 01:49:16,309 AROUND IT BUT THAT SEEMS TO BE 1922 01:49:16,309 --> 01:49:19,579 THE MOST LIKELY REASON WE'VE 1923 01:49:19,579 --> 01:49:27,487 ALWAYS HAD THIS NAGGING IN THE 1924 01:49:27,487 --> 01:49:30,157 RISK IN ASYMPTOMATIC PATIENTS. 1925 01:49:30,157 --> 01:49:38,699 I DON'T WANT ANY SCAR. 1926 01:49:38,699 --> 01:49:42,502 >> THE VENTRICULAR ATROPY I 1927 01:49:42,502 --> 01:49:44,738 DON'T THINK SHOULD BE UNDER 1928 01:49:44,738 --> 01:49:49,342 PLAYED AFTER THE MAYO CLINIC 1929 01:49:49,342 --> 01:49:52,279 DATA ABOUT THE PREDICTOR OF 1930 01:49:52,279 --> 01:49:52,646 MORTALITY. 1931 01:49:52,646 --> 01:49:55,015 I HAVE PATIENTS THAT ARE 85 1932 01:49:55,015 --> 01:50:00,020 YEARS OLD AND HAVE LGE AND HAVE 1933 01:50:00,020 --> 01:50:01,121 LIVED A LONG TIME. 1934 01:50:01,121 --> 01:50:03,590 IT'S RAY COMBINATION OF THINGS 1935 01:50:03,590 --> 01:50:06,927 IN RESPONSE TO THE VENTRICLE AND 1936 01:50:06,927 --> 01:50:09,730 NOT JUST FIBROSIS WE AND THE 1937 01:50:09,730 --> 01:50:14,735 MECHANICS AND THE TRACTION THAT 1938 01:50:14,735 --> 01:50:17,504 COULD NOT ALL MANIFEST WITH 1939 01:50:17,504 --> 01:50:23,677 FIBROSIS BUT AT THE MEC 1940 01:50:23,677 --> 01:50:25,078 MOLECULAR AND CHANNEL LEVEL. 1941 01:50:25,078 --> 01:50:27,080 WE SHOULD NOT ONLY FOCUS ON 1942 01:50:27,080 --> 01:50:28,215 FIBROSIS BUT SO MANY OTHER 1943 01:50:28,215 --> 01:50:30,450 ELEMENTS IN THE PICTURE WE 1944 01:50:30,450 --> 01:50:35,589 SHOULD PAY ATTENTION TO AND THE 1945 01:50:35,589 --> 01:50:37,891 VENTRICULAROPATHY IS VERY 1946 01:50:37,891 --> 01:50:38,158 IMPORTANT. 1947 01:50:38,158 --> 01:50:40,861 >> AND JONATHAN YOU ASKED AY 1948 01:50:40,861 --> 01:50:41,394 QUESTION. 1949 01:50:41,394 --> 01:50:43,029 THE KEY QUESTION AND WHAT I'M 1950 01:50:43,029 --> 01:50:44,698 HEARING IS WE DON'T KNOW BUT WE 1951 01:50:44,698 --> 01:50:46,767 NEED TO ANSWER IT SO I WOULD 1952 01:50:46,767 --> 01:50:51,605 PROPOSE WE NEED TO TO A CLINICAL 1953 01:50:51,605 --> 01:50:55,609 TRIAL TO ADDRESS THAT ISSUE. 1954 01:50:55,609 --> 01:50:59,312 FOR FOLKS WHO HAVE ASYMPTOMATIC 1955 01:50:59,312 --> 01:51:02,916 SEVERE MRR SHOULD WE RANDOMIZE 1956 01:51:02,916 --> 01:51:07,587 SOME PATIENTS BASED ON LGE OR 1957 01:51:07,587 --> 01:51:14,628 OTHER FEATURES AND LOOK AT 1958 01:51:14,628 --> 01:51:15,162 MECHANISTIC IMPROVEMENTS 1959 01:51:15,162 --> 01:51:15,428 FOLLOWING. 1960 01:51:15,428 --> 01:51:17,597 I THINK THAT WOULD BE A TRIAL. 1961 01:51:17,597 --> 01:51:23,303 >> WHAT ARE WE RANDOMIZING THEM 1962 01:51:23,303 --> 01:51:24,404 TO? 1963 01:51:24,404 --> 01:51:27,841 >> YOU COULD TIKE A SELECTION OF 1964 01:51:27,841 --> 01:51:30,744 PATIENTS WITH SEVERE 1965 01:51:30,744 --> 01:51:32,913 ASYMPTOMATIC MR. 1966 01:51:32,913 --> 01:51:38,151 THAT IS ALL CRITERIA ONE BUT 1967 01:51:38,151 --> 01:51:48,695 THERE ARE PEOPLE WHO STILL DO IT 1968 01:51:51,665 --> 01:51:53,567 AS 2A. 1969 01:51:53,567 --> 01:51:56,870 LOOKING AT MS. AND LGE TRIAL. 1970 01:51:56,870 --> 01:52:07,113 >> THAT WOULD BE BETTER. 1971 01:52:07,113 --> 01:52:12,319 >> I PROPOSE SEVERE MR. 1972 01:52:12,319 --> 01:52:18,325 >> THE LEFT ATRIAL FUNCTION AND 1973 01:52:18,325 --> 01:52:19,492 SO MANY MARKERS. 1974 01:52:19,492 --> 01:52:25,198 WE HAVE A SLEW OF MARKERS OF 1975 01:52:25,198 --> 01:52:30,270 OUTCOME HOW WILL YOU SAY WE HAVE 1976 01:52:30,270 --> 01:52:32,772 MARKERS AND THE PEOPLE ARE NOT 1977 01:52:32,772 --> 01:52:34,441 DOING SO WELL NATURALLY WHEN 1978 01:52:34,441 --> 01:52:39,579 THEY HAVE THOSE MARKERS AND I'M 1979 01:52:39,579 --> 01:52:43,617 SURE THAT THERE IS POTENTIAL TO 1980 01:52:43,617 --> 01:52:45,085 DO THE TRIAL BUT CAN'T JUST BE 1981 01:52:45,085 --> 01:52:48,788 FOR ONE FIBROSIS AND THE ATRIAL 1982 01:52:48,788 --> 01:52:49,489 FUNCTION. 1983 01:52:49,489 --> 01:52:52,559 YOU HAVE PLENTY OF MEASURES WE 1984 01:52:52,559 --> 01:52:58,031 CAN DO THAT MARKERS OF OUTCOME. 1985 01:52:58,031 --> 01:53:00,333 AND IS SOMEBODY WITH BNP 1986 01:53:00,333 --> 01:53:00,901 INCLUDED OR NOT? 1987 01:53:00,901 --> 01:53:02,068 THE CONSTRUCTION OF A TRIAL 1988 01:53:02,068 --> 01:53:05,605 COULD BE ANY MUCH THESE MARKERS 1989 01:53:05,605 --> 01:53:08,241 PRESENT TO TWO OR MORE PRESENT 1990 01:53:08,241 --> 01:53:15,482 TO DECIDE WHAT TO DO AND WHAT TO 1991 01:53:15,482 --> 01:53:15,749 RANDOMIZE. 1992 01:53:15,749 --> 01:53:16,149 >> 1993 01:53:16,149 --> 01:53:18,785 >> I THINK THERE'S A LOT OF 1994 01:53:18,785 --> 01:53:20,120 UNCERTAINTY AND DISCOMFORT WE 1995 01:53:20,120 --> 01:53:23,356 DON'T KNOW WHICH PATIENTS WE 1996 01:53:23,356 --> 01:53:25,292 SHOULD BE POTENTIALLY OPERATING 1997 01:53:25,292 --> 01:53:26,860 ON EARLIER, RIGHT? 1998 01:53:26,860 --> 01:53:29,896 AND TO MY POINT WE SHOULD BEING 1999 01:53:29,896 --> 01:53:31,431 TO CLINICAL TRIAL TO FIGURE OUT 2000 01:53:31,431 --> 01:53:33,300 WHO THOSE PEOPLE ARE. 2001 01:53:33,300 --> 01:53:35,602 >> JUDY, THAT'S IN MODERATE MR, 2002 01:53:35,602 --> 01:53:40,640 I AGREE. 2003 01:53:40,640 --> 01:53:42,842 THAT'S NOT AN ENROLLABLE TRIAL. 2004 01:53:42,842 --> 01:53:46,846 YOU HAVE TO GET PATIENTS WITH 2005 01:53:46,846 --> 01:53:49,849 SEVERE MR AND THE ONES WE REALLY 2006 01:53:49,849 --> 01:53:55,355 WANT TO STUDY ARE 50 AND 60 AND 2007 01:53:55,355 --> 01:53:58,658 70 NOT 80 YEAR OLDS THAT DON'T 2008 01:53:58,658 --> 01:54:00,327 WANT SURGERY. 2009 01:54:00,327 --> 01:54:03,096 I THINK I SAW 14 NEW PATIENTS 2010 01:54:03,096 --> 01:54:04,864 YESTERDAY AND 13 SIGN YOU HAD ON 2011 01:54:04,864 --> 01:54:14,007 THE TO THE -- DOT I DON'T KNOW 2012 01:54:14,007 --> 01:54:17,944 ANY NOT ASYMPTOMATIC OR IN CLASS 2013 01:54:17,944 --> 01:54:18,979 1 INTERESTED IN ACTIVE 2014 01:54:18,979 --> 01:54:19,612 SURVEILLANCE THAT'S A SMALL 2015 01:54:19,612 --> 01:54:22,749 NUMBER AND THEN YOU HAVE TO 2016 01:54:22,749 --> 01:54:23,283 RANDOMIZE THEM. 2017 01:54:23,283 --> 01:54:29,189 THE MR IS MORE INTERESTING. 2018 01:54:29,189 --> 01:54:29,990 YOU 2019 01:54:29,990 --> 01:54:32,125 >> I DISAGREE. 2020 01:54:32,125 --> 01:54:35,662 >> I SECOND DAVID AS A HUMBLE 2021 01:54:35,662 --> 01:54:36,796 CARDIOLOGIST FROM THE STANDPOINT 2022 01:54:36,796 --> 01:54:42,769 AS SOMEONE WHO LOOKED AT AN 2023 01:54:42,769 --> 01:54:46,840 ARRAY OF VIABILITY STUDIES AND 2024 01:54:46,840 --> 01:54:57,183 LOOKING AT ANGIOPROSTY AND WE'LL 2025 01:54:57,183 --> 01:55:02,389 HAVE TO LOOK AT PATIENTS WITH 2026 01:55:02,389 --> 01:55:07,527 SEVERE ENHANCEMENT AND YOU HAVE 2027 01:55:07,527 --> 01:55:11,031 TWO OTHERS OFFERING SURGERY BUT 2028 01:55:11,031 --> 01:55:12,298 MAYBE BY THE WAY WE WANT TO 2029 01:55:12,298 --> 01:55:16,002 FOLLOW YOU BUT YOU MAY BE AT 2030 01:55:16,002 --> 01:55:17,337 RISK OF SUDDEN DEATH. 2031 01:55:17,337 --> 01:55:24,511 >> THIS IS NEW YORK CITY SPEAK. 2032 01:55:24,511 --> 01:55:26,913 YOU DON'T NOT HAVE A DAVID ADAMS 2033 01:55:26,913 --> 01:55:29,949 NEXT TO THEM SO THEY HAVE TO BE 2034 01:55:29,949 --> 01:55:32,786 VERY CAREFUL THEY'LL SEND AN 2035 01:55:32,786 --> 01:55:38,291 ASYMPTOMATIC PERSON WITH NORMAL 2036 01:55:38,291 --> 01:55:39,793 FUNCTION FOR SURGERY. 2037 01:55:39,793 --> 01:55:43,563 I THINK THIS IS ENROLLABLE 2038 01:55:43,563 --> 01:55:44,831 TRIAL. 2039 01:55:44,831 --> 01:55:50,670 >> I THINK IT'S RAY SMALL NUMBER 2040 01:55:50,670 --> 01:55:58,611 OF PATIENTS. 2041 01:55:58,611 --> 01:56:02,982 PEOPLE WITH SEVERE MR THERE'S A 2042 01:56:02,982 --> 01:56:05,985 SMALLER NUMBER NORMAL AND HAVE 2043 01:56:05,985 --> 01:56:10,457 SEVERE MR AND THEY'RE INTERESTED 2044 01:56:10,457 --> 01:56:12,358 IN BEING FOLLOWED IF SOMETHING 2045 01:56:12,358 --> 01:56:14,594 WILL HAPPEN AND DON'T THINK IT'S 2046 01:56:14,594 --> 01:56:15,662 THAT LARGE A NUMBER ANYMORE. 2047 01:56:15,662 --> 01:56:26,106 >> JOE, HELP ME OUT HERE. 2048 01:56:30,910 --> 01:56:34,614 >> A LARGE NUMBER ARE 2049 01:56:34,614 --> 01:56:34,948 ASYMPTOMATIC. 2050 01:56:34,948 --> 01:56:36,583 >> IN L.A. THERE'S MORE CLIPS 2051 01:56:36,583 --> 01:56:37,183 THAN SURGERY. 2052 01:56:37,183 --> 01:56:39,586 >> NOW, NOW. 2053 01:56:39,586 --> 01:56:46,860 >> JUST SAYING. 2054 01:56:46,860 --> 01:56:52,765 IN ALL SERIOUS THE REAL QUESTION 2055 01:56:52,765 --> 01:56:55,768 IS THE MODERATE MR -- I GET BACK 2056 01:56:55,768 --> 01:56:58,838 TO CAN I SIT WITH A PATIENT AND 2057 01:56:58,838 --> 01:57:01,875 SAY YOU HAVE SEVERE MR AND SCAR 2058 01:57:01,875 --> 01:57:07,413 IN YOUR VENTRICLE AND SOLID 2059 01:57:07,413 --> 01:57:08,314 CLASS 2 INDICATION I'D LIKE TO 2060 01:57:08,314 --> 01:57:11,584 CONTINUE TO FOLLOW YOU AND TO A 2061 01:57:11,584 --> 01:57:14,354 NATURAL HISTORY STUDY AND HAVE 2062 01:57:14,354 --> 01:57:19,959 LONG ARRHYTHMIA AND MAY HAVE 2063 01:57:19,959 --> 01:57:20,160 DEATH. 2064 01:57:20,160 --> 01:57:24,197 IN MODERATE MR YOU DON'T HAVE A 2065 01:57:24,197 --> 01:57:26,699 GUIDELINE INDICATION BUT IF MY 2066 01:57:26,699 --> 01:57:29,202 HEART IS BRIGHT RED I'M LOOKING 2067 01:57:29,202 --> 01:57:31,604 FOR A SURGEON TO GET MY ANATOMY 2068 01:57:31,604 --> 01:57:32,672 BACK TO NORMAL. 2069 01:57:32,672 --> 01:57:36,976 I THINK YOU'D ENROLL IT QUICKLY 2070 01:57:36,976 --> 01:57:40,847 BUT YOU ALL HAVE TO DEFINE THE 2071 01:57:40,847 --> 01:57:42,582 IMAGING CRITERIA TO LEAD US TO 2072 01:57:42,582 --> 01:57:44,684 FEEL COMFORTABLE DOING SURGERY. 2073 01:57:44,684 --> 01:57:47,387 WE HAD THE PATIENTS BEFORE, THE 2074 01:57:47,387 --> 01:57:49,322 THREE OF US HAD THE PATIENTS 2075 01:57:49,322 --> 01:57:52,859 WITH MODERATE MR BUT THE REASON 2076 01:57:52,859 --> 01:57:58,231 WE OPERATED WAS ARRHYTHMIA 2077 01:57:58,231 --> 01:58:03,670 BURDEN BUT DON'T HAVE SEVERE MR. 2078 01:58:03,670 --> 01:58:07,607 >> WITHOUT THE SCAR AND NO 2079 01:58:07,607 --> 01:58:15,648 SURGICAL FIGURES BUT TRUE 2080 01:58:15,648 --> 01:58:18,284 COMP 2081 01:58:18,284 --> 01:58:19,352 COMP 2082 01:58:19,352 --> 01:58:21,221 COMPLEX ECTOPY. 2083 01:58:21,221 --> 01:58:24,591 >> THIS IS STILL IN THE EUROPEAN 2084 01:58:24,591 --> 01:58:27,594 GUIDELINES BUT ATRIAL 2085 01:58:27,594 --> 01:58:32,865 FIBRILLATION IS NOT INDICATED 2086 01:58:32,865 --> 01:58:39,405 FOR SURGERY FOR MR THE 2087 01:58:39,405 --> 01:58:46,846 FACILITATION OF EARLY SURGERY IN 2088 01:58:46,846 --> 01:58:51,918 U.S.-LED TO THE DISAPPEARANCE OF 2089 01:58:51,918 --> 01:59:02,161 OTHER MARKERS. 2090 01:59:03,496 --> 01:59:07,400 >> IF YOU HAVE SEVERE MR AND NON 2091 01:59:07,400 --> 01:59:08,401 SUSTAINED V.P. WHICH IS A 2092 01:59:08,401 --> 01:59:11,137 TRIGGER FOR THE DOCTOR, DOES 2093 01:59:11,137 --> 01:59:11,804 ANYONE NOT SEND THAT PATIENT FOR 2094 01:59:11,804 --> 01:59:21,948 SURGERY? 2095 01:59:43,970 --> 01:59:46,406 ATRIAL ENLARGEMENT IS HIGHER AND 2096 01:59:46,406 --> 01:59:48,574 HAVE A SLEW OF CRITERIA THAT CAN 2097 01:59:48,574 --> 01:59:50,843 BE USED. 2098 01:59:50,843 --> 01:59:55,114 I AGREE WITH DAVID NOW SURGEONS 2099 01:59:55,114 --> 01:59:58,518 TEND TO DO THE SURGERY COMPETENT 2100 01:59:58,518 --> 01:59:59,419 IN REPAIR. 2101 01:59:59,419 --> 02:00:03,156 THE PEOPLE NOT TREATED ARE THE 2102 02:00:03,156 --> 02:00:04,424 MODERATELY SEVERE MR THAT WOULD 2103 02:00:04,424 --> 02:00:06,659 BE A PERFECT CANDIDATE AND 2104 02:00:06,659 --> 02:00:08,561 ALREADY AT RISK AND I WILL SAY 2105 02:00:08,561 --> 02:00:12,432 THE TRIAL I WOULD LIKE TO DO. 2106 02:00:12,432 --> 02:00:14,467 >> BUT THE QUESTION STILL 2107 02:00:14,467 --> 02:00:15,902 STANDS, THERE'S LOTS OF PEOPLE 2108 02:00:15,902 --> 02:00:17,704 OUT THERE SITTING ON PATIENTS 2109 02:00:17,704 --> 02:00:18,538 WITH SEVERE MR. 2110 02:00:18,538 --> 02:00:20,006 I SEE IT IN THE COMMUNITY ALL 2111 02:00:20,006 --> 02:00:20,540 THE TIME. 2112 02:00:20,540 --> 02:00:26,312 WHAT I'VE NOTICED IS -- THANK 2113 02:00:26,312 --> 02:00:32,318 YOU. 2114 02:00:32,318 --> 02:00:34,487 AND I'VE NOTICED MORE 2115 02:00:34,487 --> 02:00:39,592 CARDIOLOGISTS ARE DOING MORE 2116 02:00:39,592 --> 02:00:42,328 MONITOR AND SHOWING MORE TEF TEF 2117 02:00:44,464 --> 02:00:45,098 DEF 2118 02:00:54,207 --> 02:00:55,975 WI 2119 02:00:55,975 --> 02:00:56,309 WI 2120 02:00:56,309 --> 02:01:00,213 WITH ECTOPY AND NOT DOING 2121 02:01:00,213 --> 02:01:00,680 ANYTHING? 2122 02:01:00,680 --> 02:01:03,149 >> AND NOT FOR REPAIR OF 2123 02:01:03,149 --> 02:01:04,016 REGURGITATION, I DON'T THINK 2124 02:01:04,016 --> 02:01:04,951 ACROSS THE COUNTRY 2125 02:01:04,951 --> 02:01:08,921 EVERYBODY'SIEVERYBODY'S 2126 02:01:08,921 --> 02:01:12,825 ING TO -- EVERYBODY'S DOING 2127 02:01:12,825 --> 02:01:13,025 THAT. 2128 02:01:13,025 --> 02:01:16,162 YOU'RE A UNIQUE CENTER BUT I BET 2129 02:01:16,162 --> 02:01:22,902 IF WE POLLED THE U.S. ARE THEY 2130 02:01:22,902 --> 02:01:27,473 SENDING SOMEBODY TO SURGERY 2131 02:01:27,473 --> 02:01:30,309 >> IT'S A WHEN THEY HAVE 2132 02:01:30,309 --> 02:01:35,314 MALIGNANT OR SEMI MALIGNANT 2133 02:01:35,314 --> 02:01:40,219 ARRHYTHMIAS AND KEEPS GET 2134 02:01:40,219 --> 02:01:50,663 THERAPIES FOR THE MONITOR. 2135 02:01:52,165 --> 02:01:54,434 PEOPLE MAY SAY LET ME PUSH THEM 2136 02:01:54,434 --> 02:01:55,835 FOR SURGERY AND LESSER THAN 2137 02:01:55,835 --> 02:01:56,335 SEVERE I DON'T THINK IS 2138 02:01:56,335 --> 02:02:04,577 HAPPENING. 2139 02:02:04,577 --> 02:02:06,813 MORE ARE BEING REFERRED BECAUSE 2140 02:02:06,813 --> 02:02:09,115 OF THE MONITOR AND MR. 2141 02:02:09,115 --> 02:02:11,417 >> MY HYPOTHESIS IS THE EFFECT 2142 02:02:11,417 --> 02:02:14,654 OF SURGERY IS TO REDUCE THE 2143 02:02:14,654 --> 02:02:18,024 ABNORMAL DYNAMIC ON THE 2144 02:02:18,024 --> 02:02:19,091 PAPILLARY MUSCLE TO REDUCE 2145 02:02:19,091 --> 02:02:20,259 ARRHYTHMIA BURDEN. 2146 02:02:20,259 --> 02:02:22,862 IT NEEDS TO BE PROVEN STILL BUT 2147 02:02:22,862 --> 02:02:27,967 NEED TO BE IN THE HYPOTHESIS. 2148 02:02:27,967 --> 02:02:38,144 >> SHOULD 2149 02:02:54,227 --> 02:02:56,462 >> I WISH WE COULD TO THIS 2150 02:02:56,462 --> 02:02:58,898 ANOTHER HOUR I'M LEARNING A LOT 2151 02:02:58,898 --> 02:03:03,636 AND LEARNING ABOUT THE GOALS OF 2152 02:03:03,636 --> 02:03:05,738 MITRAL VALVE REPAIR AND SURGERY. 2153 02:03:05,738 --> 02:03:07,607 I ALWAYS SAY TO PATIENTS, NATURE 2154 02:03:07,607 --> 02:03:09,809 DOESN'T MAKE MISTAKES. 2155 02:03:09,809 --> 02:03:14,614 IF WANTED US TO HAVE A DOUBLE 2156 02:03:14,614 --> 02:03:21,254 BARREL SEPTUM IT WOULD DO THAT 2157 02:03:21,254 --> 02:03:25,424 AND I THINK THESE PERTURBATIONS 2158 02:03:25,424 --> 02:03:25,925 INCLUDING THE STEEZ BUT 2159 02:03:25,925 --> 02:03:29,562 PROLAPSES BY ASKING ABOUT VOLUME 2160 02:03:29,562 --> 02:03:31,831 VERSUS SIZE OF LEAFLETS THEY ARE 2161 02:03:31,831 --> 02:03:33,399 ALL CREATE TENSION AND THE 2162 02:03:33,399 --> 02:03:35,935 NORMAL VALVE APPARATUS IS TO TRY 2163 02:03:35,935 --> 02:03:41,207 TO MINIMIZE TENSION WHICH IS WHY 2164 02:03:41,207 --> 02:03:44,110 IS RECURRENT PROLAPSE SO 2165 02:03:44,110 --> 02:03:45,044 UNUSUAL? 2166 02:03:45,044 --> 02:03:48,681 WHY DON'T MORE CHORDS ELONGATE 2167 02:03:48,681 --> 02:03:50,650 AND RUPTURE? 2168 02:03:50,650 --> 02:03:58,624 WE THINK TENSION ON THE LEAVE 2169 02:03:58,624 --> 02:04:03,596 -- LEAFLETS ON THE APPARATUS 2170 02:04:03,596 --> 02:04:05,898 AND SAME IS TRUE FOR FLOW AND 2171 02:04:05,898 --> 02:04:09,302 FLOW AND DIASTOLIC PERFORMS OF 2172 02:04:09,302 --> 02:04:11,270 VALVES PROBABLY INFLUENCES THE 2173 02:04:11,270 --> 02:04:12,505 VENTRICLE AS WELL. 2174 02:04:12,505 --> 02:04:18,044 NONE OF THIS IS PROVABLE YET BUT 2175 02:04:18,044 --> 02:04:22,915 I BELIEVE NATURE IS RIGHT AND I 2176 02:04:22,915 --> 02:04:28,988 HAVE A HUNCH MITRAL VALVE AFLNAT 2177 02:04:28,988 --> 02:04:31,991 ANATOMY IS THAT WAY FOR A REASON 2178 02:04:31,991 --> 02:04:40,900 AND IT CREATES ABNORMAL TENSION. 2179 02:04:40,900 --> 02:04:45,371 >> THIS HAS BEEN A FASCINATING 2180 02:04:45,371 --> 02:04:47,540 DISCUSSION, THANK YOU, FOLKS. 2181 02:04:47,540 --> 02:04:49,041 YOU MAY RECALL A QUESTION I HAD 2182 02:04:49,041 --> 02:04:51,243 DEFERRED ON THE VIDEOCAST AND 2183 02:04:51,243 --> 02:04:55,581 THE QUESTION CAME IN SHORTLY 2184 02:04:55,581 --> 02:04:57,783 AFTER JUDY'S PRESENTATION. 2185 02:04:57,783 --> 02:05:00,720 IS THE ETIOLOGY OF PROLAPSE 2186 02:05:00,720 --> 02:05:07,593 GENETIC OR CAUSED BY OTHER 2187 02:05:07,593 --> 02:05:10,863 DISEASES SUCH AS MI. 2188 02:05:10,863 --> 02:05:12,865 DOES ANYONE CARE TO TAKE THAT? 2189 02:05:12,865 --> 02:05:14,367 >> NO. 2190 02:05:14,367 --> 02:05:18,037 >> WE DON'T KNOW FOR SURE. 2191 02:05:18,037 --> 02:05:20,606 THERE'S SOME GENETIC 2192 02:05:20,606 --> 02:05:22,675 PREDISPOSITION TOMORROW OR THIS 2193 02:05:22,675 --> 02:05:24,076 AFTERNOON. 2194 02:05:24,076 --> 02:05:27,980 WE KNOW THERE IS SOME FAMILIAL 2195 02:05:27,980 --> 02:05:28,180 STORY. 2196 02:05:28,180 --> 02:05:29,281 WE'LL LEARN MORE TODAY OR 2197 02:05:29,281 --> 02:05:29,548 TOMORROW. 2198 02:05:29,548 --> 02:05:33,085 I DON'T THINK -- I WILL SAY THAT 2199 02:05:33,085 --> 02:05:35,554 ONE OF THE THEORIES INCREASINGLY 2200 02:05:35,554 --> 02:05:37,556 AM INTERESTED IN AND FRANK WELSH 2201 02:05:37,556 --> 02:05:39,659 USED TO TALK ABOUT WHICH IS THE 2202 02:05:39,659 --> 02:05:44,830 ABNORMAL ANATOMY THAT CREATES 2203 02:05:44,830 --> 02:05:47,066 TENSION THAT ULTIMATELY LEAD TO 2204 02:05:47,066 --> 02:05:49,468 PROLAPSE AND JUDY HAD A 2205 02:05:49,468 --> 02:05:52,705 BEAUTIFUL CASE WITH A DEEP 2206 02:05:52,705 --> 02:05:55,341 INDENTATION A RESEGMENT VALVE 2207 02:05:55,341 --> 02:06:04,884 BUZ THE INDENTATION GOES TO THE 2208 02:06:04,884 --> 02:06:09,889 ANNULUS AND IT CREATES 2209 02:06:09,889 --> 02:06:13,526 COMMISEWER AND THE MORE I DO THE 2210 02:06:13,526 --> 02:06:19,298 MORE I REALIZE MANY TIMES YOU'RE 2211 02:06:19,298 --> 02:06:26,505 DOING REPAIRS WITH A MULTI- 2212 02:06:26,505 --> 02:06:29,375 MULTI-SEGMENTED LEAFLET AND 2213 02:06:29,375 --> 02:06:33,713 ANATOMY MAY DICTATE THAT TOO 2214 02:06:33,713 --> 02:06:36,782 SOMETIMES AND VARIANCE OF MITRAL 2215 02:06:36,782 --> 02:06:39,251 VALVE ANATOMY ARE MORE PRONE TO 2216 02:06:39,251 --> 02:06:41,320 DISEASE BECAUSE OF THE LEAFLETS. 2217 02:06:41,320 --> 02:06:43,055 IT'S PROBABLY WHY WE'RE SUPPOSED 2218 02:06:43,055 --> 02:06:53,566 TO HAVE TWO SEGMENTS AND TWO 2219 02:07:02,541 --> 02:07:02,775 COMMISURES. 2220 02:07:02,775 --> 02:07:04,643 >> THAT WAS THE CHIME. 2221 02:07:04,643 --> 02:07:05,778 DOES ANYONE HAVE FINAL QUESTIONS 2222 02:07:05,778 --> 02:07:06,479 OR COMMENTS? 2223 02:07:06,479 --> 02:07:10,249 >> I WANT TO THANK EVERYONE FOR 2224 02:07:10,249 --> 02:07:16,889 A PHENOMENAL SESSION AND 2225 02:07:16,889 --> 02:07:19,592 DISCUSSION IT WILL INFORM 2226 02:07:19,592 --> 02:07:20,359 RESEARCH AND TRIELGZ AND MUCH OF 2227 02:07:20,359 --> 02:07:22,661 THE IMAGING WORK WILL BE 2228 02:07:22,661 --> 02:07:25,231 ENHANCED AND FOCUSSED BASED ON 2229 02:07:25,231 --> 02:07:27,032 ADDITIONAL RESEARCH ADVANCEMENTS 2230 02:07:27,032 --> 02:07:28,901 IN TERMS OF CARDIOVASCULAR 2231 02:07:28,901 --> 02:07:32,905 GENETICS IN OTHER ANCILLARY 2232 02:07:32,905 --> 02:07:33,806 MARKERS TO INFORM ADDITIONAL 2233 02:07:33,806 --> 02:07:34,874 PRECISION AND THAT'S CRITICAL 2234 02:07:34,874 --> 02:07:36,675 AND LOOKING FORWARD TO FUTURE 2235 02:07:36,675 --> 02:07:37,777 SESSION TO FOLLOW UP AND 2236 02:07:37,777 --> 02:07:38,043 TOMORROW. 2237 02:07:38,043 --> 02:07:39,912 THANKS VERY MUCH. 2238 02:07:39,912 --> 02:07:41,147 >> THANK YOU, EVERYONE. 2239 02:07:41,147 --> 02:07:43,516 I PROPOSE THAT WE GO AHEAD AND 2240 02:07:43,516 --> 02:07:46,285 TAKE OUR BREAK NOW UNTIL 40 2241 02:07:46,285 --> 02:07:51,390 MINUTES AFTER THE HOUR PUTTING 2242 02:07:51,390 --> 02:08:08,196 US BACK ON SCHEDULE. 2243 02:08:08,196 --> 02:08:14,535 OUR FIRST SPEAKER IS 2244 02:08:14,535 --> 02:08:16,337 FRANCESSCA DELLING. 2245 02:08:16,337 --> 02:08:17,905 >> THANK YOU FOR THE OPPORTUNITY 2246 02:08:17,905 --> 02:08:25,847 TO SPEAK ABOUT OUR WORK ON 2247 02:08:25,847 --> 02:08:29,250 PHENOTYPIC PEDIGREES. 2248 02:08:29,250 --> 02:08:32,954 THIS WORK IS FUNDED BY THE CAROL 2249 02:08:32,954 --> 02:08:43,164 ACT AND PRIOR R03 GRANT. 2250 02:08:43,164 --> 02:08:46,300 I WON'T SPEND TIME ON THE 2251 02:08:46,300 --> 02:08:46,601 DEFINITION. 2252 02:08:46,601 --> 02:08:50,838 IT VARIES A LOT WITH STUDIES AND 2253 02:08:50,838 --> 02:08:54,409 I UTILIZED THE DEFINITION OF A 2254 02:08:54,409 --> 02:08:56,577 CONSENSUS STATEMENT PUBLISHED IN 2255 02:08:56,577 --> 02:09:04,419 2022 WHICH IT CAN DEFINES IT 2256 02:09:04,419 --> 02:09:11,793 FREQUENT OR COMPLEX VENTRICULAR 2257 02:09:11,793 --> 02:09:15,863 ECTOPY AND THE HIGHEST IN SEVERE 2258 02:09:15,863 --> 02:09:19,400 REGURGITATION AND CARDIAC 2259 02:09:19,400 --> 02:09:24,372 IMAGING ESSENTIAL TO IDENTIFY 2260 02:09:24,372 --> 02:09:32,947 THOSE AT RISK. 2261 02:09:32,947 --> 02:09:34,916 SOME AT RISK MENTIONED BY 2262 02:09:34,916 --> 02:09:36,250 DR. HUNG, I'LL BRIEF GO OVER 2263 02:09:36,250 --> 02:09:39,020 THEM AGAIN BECAUSE WE DID 2264 02:09:39,020 --> 02:09:40,421 UTILIZE THEM FOR THE PHENOTYPING 2265 02:09:40,421 --> 02:09:47,962 IN THE PED FWIGPEDIGREES. 2266 02:09:47,962 --> 02:09:51,132 THE LEAFLET PHENOTYPE IS 2267 02:09:51,132 --> 02:09:53,367 IMPORTANT AND YOU SEE THE 2268 02:09:53,367 --> 02:09:57,004 CURLING WITH THE MOTION AT THE 2269 02:09:57,004 --> 02:09:59,907 INTRAL LATERAL BASE OF THE LEFT 2270 02:09:59,907 --> 02:10:04,078 VENTRICLE WHICH CAN BE CAPTURED 2271 02:10:04,078 --> 02:10:07,014 NICELY BY THE INCREASED VELOCITY 2272 02:10:07,014 --> 02:10:16,724 AT THE LATERAL ANNULUS. 2273 02:10:16,724 --> 02:10:21,929 THIS IS A SCHEMATIC AT THE BASE 2274 02:10:21,929 --> 02:10:23,764 WITH THE TRACTION OF THE 2275 02:10:23,764 --> 02:10:25,333 PROLAPSING LEAFLETS IN THE 2276 02:10:25,333 --> 02:10:32,039 MUSCLE AND MYOCARDIUM. 2277 02:10:32,039 --> 02:10:38,513 MECHANICS CAN BE MEASURED BY 2278 02:10:38,513 --> 02:10:43,818 PARAMETERS PUBLISHED IN A NUMBER 2279 02:10:43,818 --> 02:10:46,854 OF PAPERS INCLUDING THE DOUBLE 2280 02:10:46,854 --> 02:10:50,992 PEAK PATTERN AND POST SYSTEMIC 2281 02:10:50,992 --> 02:10:52,760 SHORTENING INDEX CALCULATED WITH 2282 02:10:52,760 --> 02:10:56,364 THE FORMULA SHOWN HERE AND 2283 02:10:56,364 --> 02:10:59,400 MECHANICAL DISPERSION WE 2284 02:10:59,400 --> 02:11:01,736 PUBLISHED YEARS AGO BASICALLY 2285 02:11:01,736 --> 02:11:05,306 DEMONSTRATING HETEROGENEOUS 2286 02:11:05,306 --> 02:11:12,446 CONTRACTION AND COULD BE 2287 02:11:12,446 --> 02:11:16,450 ELECTRICAL DISPERSION AND IS 2288 02:11:16,450 --> 02:11:22,390 SEEN AND CARDIO MYOPATHY WITHOUT 2289 02:11:22,390 --> 02:11:24,725 PROLAPSE AND THIS WILL COME UP 2290 02:11:24,725 --> 02:11:25,526 IN THE DISCUSSION OF THE 2291 02:11:25,526 --> 02:11:35,903 PEDIGREE PHENOTYPING. 2292 02:11:37,605 --> 02:11:44,345 AS A RESULT OF THE BASE SHOWN BY 2293 02:11:44,345 --> 02:11:48,716 THIS BOSTON GROUP. 2294 02:11:48,716 --> 02:11:51,319 IN TERMS OF GENETICS THERE'S NOT 2295 02:11:51,319 --> 02:11:57,058 A LARGE DATA SET SO FAR. 2296 02:11:57,058 --> 02:11:59,093 GENETICS ARE LIMIT TO CASE 2297 02:11:59,093 --> 02:12:00,328 STUDIES. 2298 02:12:00,328 --> 02:12:05,766 THE GENETICS FOR WHAT I'LL BE 2299 02:12:05,766 --> 02:12:06,968 DESCRIBING IS UNDERGOING AND 2300 02:12:06,968 --> 02:12:09,837 FOCUSSING ON THE PHENOTYPING 2301 02:12:09,837 --> 02:12:12,907 WHICH HAS LED TO INTERESTING 2302 02:12:12,907 --> 02:12:13,608 DISCOVERIES. 2303 02:12:13,608 --> 02:12:15,009 THE INTEREST IN DETAILED 2304 02:12:15,009 --> 02:12:17,411 PHENOTYPING HAS COME FROM THE 2305 02:12:17,411 --> 02:12:21,148 FACT THAT FIRST OF ALL FAMILY 2306 02:12:21,148 --> 02:12:22,917 HISTORY OF PROLAPSE HAS ONLY 2307 02:12:22,917 --> 02:12:25,653 BEEN REPORTED IN SMALL 2308 02:12:25,653 --> 02:12:27,521 PATHOLOGICAL AND THE ARRHYTHMIC 2309 02:12:27,521 --> 02:12:31,492 CAUSE OF DEATH OF THE CASES WITH 2310 02:12:31,492 --> 02:12:33,628 SUDDEN DEATH NOT BEEN 2311 02:12:33,628 --> 02:12:36,697 CORROBORATED SO THE RISK OF 2312 02:12:36,697 --> 02:12:38,132 AFAMILIAR RISK IN MVP IS UNCLEAR 2313 02:12:38,132 --> 02:12:39,967 AND THE INHERITANCE OF THE 2314 02:12:39,967 --> 02:12:46,040 PHENOTYPIC IMAGING FEATURES OF 2315 02:12:46,040 --> 02:12:49,043 ARRHYTHMIC MVP REMAINS POORLY 2316 02:12:49,043 --> 02:12:53,581 DEFINED SO FAR AT THIS LEVEL. 2317 02:12:53,581 --> 02:13:00,421 THIS IS ONE OF THE CASE SERIES 2318 02:13:00,421 --> 02:13:07,528 ABOUT GENETICS AND ARRHYTHMIC 2319 02:13:07,528 --> 02:13:11,032 MVP AND THIS SHOWS A GENE WHICH 2320 02:13:11,032 --> 02:13:15,703 PLAY SERVE AS A SUBSTRATE FOR 2321 02:13:15,703 --> 02:13:16,504 LEAFLET MVP. 2322 02:13:16,504 --> 02:13:18,306 THIS IS FOUR INDIVIDUAL 2323 02:13:18,306 --> 02:13:24,445 SEQUENCING STUDY BUT IT 2324 02:13:24,445 --> 02:13:26,113 INTRODUCES THE INTERESTING POINT 2325 02:13:26,113 --> 02:13:28,282 THERE MAY BE A GENETIC SUBSTRATE 2326 02:13:28,282 --> 02:13:31,852 UNDERLYING THE MOST SEVERE CASES 2327 02:13:31,852 --> 02:13:36,157 OF ARRHYTHMIC COMPLICATIONS AND 2328 02:13:36,157 --> 02:13:41,595 WEAK MYOCYTE COUPLING AND HAVE A 2329 02:13:41,595 --> 02:13:49,270 TRIG 2330 02:13:49,270 --> 02:13:50,338 TRIGGER AND THIS IS IMPORTANT 2331 02:13:50,338 --> 02:13:59,013 FOR THE DATA I'LL PRESENT NEXT. 2332 02:13:59,013 --> 02:14:04,418 THERE'S A CASE REPORT ALLOWING A 2333 02:14:04,418 --> 02:14:11,959 CARDIO MYOPATHY GENE AND A 2334 02:14:11,959 --> 02:14:14,095 CHANNELOPATHY GENE WITH SEVERE 2335 02:14:14,095 --> 02:14:24,338 PERTURBATION. 2336 02:14:26,006 --> 02:14:31,979 THIS LOOKED AT STUDYING SUDDEN 2337 02:14:31,979 --> 02:14:33,981 DEATH OF THE YOUNG WITH WHOLE 2338 02:14:33,981 --> 02:14:36,884 EXOME SEQUENCING AND SIX 2339 02:14:36,884 --> 02:14:38,185 INDIVIDUALS WITH MITRAL VALVE 2340 02:14:38,185 --> 02:14:40,421 PROLAPSE AND THREE WERE 2341 02:14:40,421 --> 02:14:42,690 HIGHLIGHTED LIKELY PATHOGENIC 2342 02:14:42,690 --> 02:14:50,231 VARIANTS RELATED TO CARDIO MY 2343 02:14:50,231 --> 02:14:55,903 ON -- CARDIO MYOPATHY OR 2344 02:14:55,903 --> 02:14:56,337 CHANNELOPATHY GENE. 2345 02:14:56,337 --> 02:14:59,206 THANKS TO A SUPPLEMENT FROM MY 2346 02:14:59,206 --> 02:15:02,209 R1 I WAS ABLE TOE STUDY THE 2347 02:15:02,209 --> 02:15:04,445 SUDDEN DEATH OR ARREST IN A 2348 02:15:04,445 --> 02:15:09,250 NUMBER OF MVP PEDIGREES AT UCSF 2349 02:15:09,250 --> 02:15:11,719 AND LEVERAGING THE LARGE 2350 02:15:11,719 --> 02:15:15,990 COLLECTION AND THIS POSTMORTEM 2351 02:15:15,990 --> 02:15:19,493 INVESTIGATION OF POST CARDIAC 2352 02:15:19,493 --> 02:15:23,264 SUDDEN DEATH FOR TRUE ARRHYTHMIC 2353 02:15:23,264 --> 02:15:27,435 CAUSE OF DEATH AND IDENTIFY 2354 02:15:27,435 --> 02:15:30,438 PARAMETERS USING CARDIO GRAPHY 2355 02:15:30,438 --> 02:15:33,240 IN PEDIGREES WITH SUDDEN DEATH 2356 02:15:33,240 --> 02:15:36,744 OR ATROPHY AND WANTED TO COMPARE 2357 02:15:36,744 --> 02:15:39,713 FAMILY MEMBERS WITH NON-PROLAPSE 2358 02:15:39,713 --> 02:15:45,352 TO NON-PEDIGREE HEALTHY CONTROLS 2359 02:15:45,352 --> 02:15:48,422 TO IDENTIFY INDEPENDENT OF MVP 2360 02:15:48,422 --> 02:15:50,758 EXPRESSION. 2361 02:15:50,758 --> 02:15:53,727 SO WE LEVERAGED OUR UCSF 2362 02:15:53,727 --> 02:15:58,232 REGISTRY TO IDENTIFY PEDIGREES. 2363 02:15:58,232 --> 02:15:59,934 THIS INCLUDES OVER 700 CASES 2364 02:15:59,934 --> 02:16:04,171 FROM THE ECHO DATABASE AND HAVE 2365 02:16:04,171 --> 02:16:07,208 TRACKING AND STANDARD ECHO 2366 02:16:07,208 --> 02:16:13,147 VARIABLES AS WELL AS CLINICAL 2367 02:16:13,147 --> 02:16:13,414 VARIABLES. 2368 02:16:13,414 --> 02:16:20,187 ALL HAVE SAMPLES FOR GENOMICS 2369 02:16:20,187 --> 02:16:23,858 AND IDENTIFIED 23 WITH MVP AND 2370 02:16:23,858 --> 02:16:25,993 THE TOTAL OF 121 FAMILY MEMBERS 2371 02:16:25,993 --> 02:16:30,364 COLLECTED. 2372 02:16:30,364 --> 02:16:37,805 SO THIS IS THE STUDY WHICH IS 2373 02:16:37,805 --> 02:16:45,813 STRENGTHENED WITH AUTOPSY ON 100 2374 02:16:45,813 --> 02:16:50,217 WHO TEE FIND SCD ABLED 18 TO 90. 2375 02:16:50,217 --> 02:16:52,186 THERE'S NO SELECTION BIAS. 2376 02:16:52,186 --> 02:16:55,589 THIS IS ALL COMERS. 2377 02:16:55,589 --> 02:17:01,161 IT WAS A HIGH AUTOPSY RATE IN 2378 02:17:01,161 --> 02:17:05,666 POSTMORTEM PHENOTYPES IN CAUSE 2379 02:17:05,666 --> 02:17:10,471 WAS BASED ON EXCLUSION OF OTHER 2380 02:17:10,471 --> 02:17:13,874 ETIOLOGIES OF SUDDEN DEATH WHICH 2381 02:17:13,874 --> 02:17:14,608 MIMIC ARRHYTHMIC DEATH AND 2382 02:17:14,608 --> 02:17:18,913 EPILEPSY OR DRUG OVERDOSES. 2383 02:17:18,913 --> 02:17:29,456 AND THE PREVALENCE OF MVP WAS 4% 2384 02:17:29,924 --> 02:17:37,665 SUDDEN ARRHYTHMIC DEATHS. 2385 02:17:37,665 --> 02:17:40,434 WE LEVERAGED THE HEALTHY START 2386 02:17:40,434 --> 02:17:44,104 STUDY ALSO A UCSF STUDY LARGE 2387 02:17:44,104 --> 02:17:52,446 COHORT OF ADULTS A SET WITHOUT 2388 02:17:52,446 --> 02:17:59,153 KNOWN CARDIOVASCULAR DISEASE AND 2389 02:17:59,153 --> 02:18:09,496 PARAMETERS AT UCSF. 2390 02:18:10,264 --> 02:18:15,636 AND TWO DEATHS WERE FROM THE 2391 02:18:15,636 --> 02:18:15,869 STUDY. 2392 02:18:15,869 --> 02:18:26,380 FOUR HAD 121 PARTICIPANTS AND 2393 02:18:31,018 --> 02:18:32,686 THE SPECTRUM IDENTIFIED. 2394 02:18:32,686 --> 02:18:38,659 WE HAVE NORMAL INDIVIDUALS WHICH 2395 02:18:38,659 --> 02:18:49,103 HAVE A LOW POINT AND AND 2396 02:19:12,493 --> 02:19:14,962 MEASURED THE DYSFUNCTION AND 2397 02:19:14,962 --> 02:19:25,506 ALSO AND A TOTAL OF FOUR CASES 2398 02:19:48,462 --> 02:19:58,906 IN THE GROUP AND THE CARDIAC 2399 02:20:15,622 --> 02:20:18,859 CASES WERE FOUND IN 14%. 2400 02:20:18,859 --> 02:20:20,694 SO PARTICIPANTS ALSO WERE 2401 02:20:20,694 --> 02:20:23,697 RECONTACTED SIX YEARS AFTER THE 2402 02:20:23,697 --> 02:20:26,767 INITIAL RECRUITMENT AND IN CA 2403 02:20:26,767 --> 02:20:30,938 CASE -- NO CASE OF DEATH WERE 2404 02:20:30,938 --> 02:20:33,907 IDENTIFIED AND NONE HAD A 2405 02:20:33,907 --> 02:20:36,443 HISTORY OF CORONARY DISEASE OR 2406 02:20:36,443 --> 02:20:45,452 VALVE DISEASE. 2407 02:20:45,452 --> 02:20:55,996 AND THEY AND WE HAD ARRHYTHMIC 2408 02:20:57,965 --> 02:21:00,701 AND NON ARRHYTHMIC AND WHEN LG 2409 02:21:00,701 --> 02:21:02,970 WAS PRESENT WAS IN THE TYPICAL 2410 02:21:02,970 --> 02:21:04,972 LOCATIONS OF THE PATHWAY MUSCLES 2411 02:21:04,972 --> 02:21:11,245 OR BASAL INTRALATERAL WALL. 2412 02:21:11,245 --> 02:21:15,115 THESE ARE THE RESULTS OF THE 2413 02:21:15,115 --> 02:21:15,616 ANALYSIS. 2414 02:21:15,616 --> 02:21:17,751 WE ASSESSED THE LONGITUDINAL 2415 02:21:17,751 --> 02:21:19,453 STRAIN AND MECHANICAL DISPERSION 2416 02:21:19,453 --> 02:21:20,087 AND DOUBLE PEAK. 2417 02:21:20,087 --> 02:21:24,992 SAME PATTERN. 2418 02:21:24,992 --> 02:21:34,701 THERE WAS NO DIFFERENCE AND THE 2419 02:21:34,701 --> 02:21:37,638 PEAK STRAIN PATTERN WAS NOT IN 2420 02:21:37,638 --> 02:21:40,474 THE NORMAL VALVES. 2421 02:21:40,474 --> 02:21:44,211 INTERESTINGLY THE ARRHYTHMIC 2422 02:21:44,211 --> 02:21:48,315 PEAK HAD MORE STRAIN IN THE 2423 02:21:48,315 --> 02:21:51,285 BASAL WALL AND OF INTEREST THE 2424 02:21:51,285 --> 02:21:54,888 ARRHYTHMIC MVPs HAD INTRALATERAL 2425 02:21:54,888 --> 02:21:58,325 PSI TYPICAL AREAS OF TRACTION 2426 02:21:58,325 --> 02:22:04,431 BUT ALSO HAD ABNORMAL PSI NOT 2427 02:22:04,431 --> 02:22:07,100 SUBJECT TO TRACTION. 2428 02:22:07,100 --> 02:22:10,871 THE APEX AND SEPTUM OR 2429 02:22:10,871 --> 02:22:13,540 INTRALATERAL WALL AND ARRHYTHMIC 2430 02:22:13,540 --> 02:22:19,847 MVP HAD SINGLE PSI VALUES 2431 02:22:19,847 --> 02:22:21,114 COMPARED TO THOSE WITHOUT SUDDEN 2432 02:22:21,114 --> 02:22:31,391 CARDIAC ARREST. 2433 02:22:41,235 --> 02:22:50,777 AND THE MAIN POINT OF ARREST WAS 2434 02:22:50,777 --> 02:22:55,082 IN 14% OF PEDIGREE SO THEY'RE 2435 02:22:55,082 --> 02:22:58,919 ALL LOW AND THE STRAIN IN 2436 02:22:58,919 --> 02:23:00,354 ARRHYTHMIC MVP IN THE FAMILIAR 2437 02:23:00,354 --> 02:23:01,822 SETTING IS PRESENT NOT JUST IN 2438 02:23:01,822 --> 02:23:06,260 THE TYPICAL AREAS OF TRACTION 2439 02:23:06,260 --> 02:23:09,263 BUT DIFFUSED SUGGESTING A 2440 02:23:09,263 --> 02:23:12,566 MYOPATHIC PROCESS AND LOOKING AT 2441 02:23:12,566 --> 02:23:13,767 INDIVIDUALS OUTSIDE THE SETTING 2442 02:23:13,767 --> 02:23:16,169 AND CONTROLS FROM THE HEALTHY 2443 02:23:16,169 --> 02:23:18,205 HEART STUDY WITH NORMAL VALVES 2444 02:23:18,205 --> 02:23:23,210 AND COMPARED THEM WITH THE 2445 02:23:23,210 --> 02:23:25,145 FAMILY MEMBERS WITH NORMAL 2446 02:23:25,145 --> 02:23:26,880 VALVES THE INDIVIDUALS WITHIN 2447 02:23:26,880 --> 02:23:34,721 PEDIGREES BUT HAD HIGH 2448 02:23:34,721 --> 02:23:38,792 MECHANICAL DISPERSION AND LOWER 2449 02:23:38,792 --> 02:23:41,061 STRAIN. 2450 02:23:41,061 --> 02:23:48,535 AND AGAIN INDICATE IING THE PROS 2451 02:23:48,535 --> 02:23:49,603 EVEN INDEPENDENT OF PROLAPSED 2452 02:23:49,603 --> 02:23:59,813 EXPRESSION. 2453 02:24:04,151 --> 02:24:09,723 STUDYING CARI AC ARREST WE FOUND 2454 02:24:09,723 --> 02:24:19,433 IN 33% OF CASES INSTEAD CARDIAC 2455 02:24:19,433 --> 02:24:23,870 ARREST MAY REQUIRE A COMBINATION 2456 02:24:23,870 --> 02:24:26,606 OF MYOCARDIAL MECHANICS AS 2457 02:24:26,606 --> 02:24:28,542 EXPRESSED BY HIGHER ELECTRICAL 2458 02:24:28,542 --> 02:24:30,444 MECHANICAL DISPERSION AND FAMILY 2459 02:24:30,444 --> 02:24:34,181 MEMBERS WITH NORMAL MITRAL 2460 02:24:34,181 --> 02:24:37,951 VALVES HAVE EXHIBIT PARAMETERS 2461 02:24:37,951 --> 02:24:40,320 SUGGESTING AN UNDERLYING 2462 02:24:40,320 --> 02:24:45,659 MYOPATHY IN INDEPENDENT OF 2463 02:24:45,659 --> 02:24:46,760 EXPRESSION AND SUDDEN DEATH 2464 02:24:46,760 --> 02:24:48,428 REQUIRES THE CONCEPT FIRST 2465 02:24:48,428 --> 02:24:52,199 INTRODUCED BY THE MAYO CLINIC 2466 02:24:52,199 --> 02:24:54,801 PAPER SO TWO-HIT MODEL OF THE 2467 02:24:54,801 --> 02:24:57,237 PRESENCE OF A NORMAL MECHANICS 2468 02:24:57,237 --> 02:25:07,748 IN A PRIMARY GENETIC MYOPATHY. 2469 02:25:10,384 --> 02:25:15,022 I'D LIKE TO THANK MY TEAM AND MY 2470 02:25:15,022 --> 02:25:17,758 COLLABORATORS DR. SCHILLER AT 2471 02:25:17,758 --> 02:25:20,060 UCSF WHO PROVIDED THE HEALTHY 2472 02:25:20,060 --> 02:25:27,234 HEART CONTROLS AND CHIP AND 2473 02:25:27,234 --> 02:25:29,703 COURTNEY WORKING ON THE GENETICS 2474 02:25:29,703 --> 02:25:31,671 AND BOB WHO HAS LAID A SECOND 2475 02:25:31,671 --> 02:25:38,512 PAIR OF EYES ON MY MOST 2476 02:25:38,512 --> 02:25:45,018 DIFFICULT CONUNDRUMS IN THE 2477 02:25:45,018 --> 02:25:46,053 PEDIGREES. 2478 02:25:46,053 --> 02:25:46,953 >> THANK YOU. 2479 02:25:46,953 --> 02:25:48,088 DOES ANYONE HAVE ANY QUESTION OR 2480 02:25:48,088 --> 02:25:48,688 COMMENT ABOUT THIS PARTICULAR 2481 02:25:48,688 --> 02:25:58,932 PRESENTATION? 2482 02:26:08,141 --> 02:26:09,242 >> WE HAD THE SAME OBSERVATION 2483 02:26:09,242 --> 02:26:12,446 SO I LIKED IT VERY MUCH. 2484 02:26:12,446 --> 02:26:21,721 >> AGREED. 2485 02:26:21,721 --> 02:26:25,492 >> WE HAVE TWO PEDIGREES AND 2486 02:26:25,492 --> 02:26:31,098 THERE'S NO REOCCURRENCE OR RARE 2487 02:26:31,098 --> 02:26:36,436 REOCCURRENCE IN FAMILIES OF 2488 02:26:36,436 --> 02:26:46,813 MITRAL VALVE COLLAPSE. 2489 02:26:51,384 --> 02:26:56,923 AND LOOK AT THE DISEASE IN 2490 02:26:56,923 --> 02:27:00,427 SIGNIFICANT PART OF OUR 2491 02:27:00,427 --> 02:27:10,704 POPULATION AND LOOKS AT CAUTIONS 2492 02:27:10,704 --> 02:27:21,248 AND ALSO IN SOME CASES WE DON'T 2493 02:27:23,283 --> 02:27:24,851 FIND ANYTHING BUT DON'T KNOW IF 2494 02:27:24,851 --> 02:27:32,425 IT FINDS THE CAUSES OF SUDDEN 2495 02:27:32,425 --> 02:27:42,969 DEATH AND HAVE A PAPER AND IN 2496 02:27:51,244 --> 02:27:57,184 THE SPECIFIC MUTATION WITH SEVEN 2497 02:27:57,184 --> 02:28:04,624 FAMILIES I THINK WE FOUND TE 2498 02:28:04,624 --> 02:28:08,461 LARGEST DELETION IN THE GEEM AND 2499 02:28:08,461 --> 02:28:13,934 VARIANT IN THE GENE THAT LEAD TO 2500 02:28:13,934 --> 02:28:15,502 THIS AND TO MITRAL VALVE 2501 02:28:15,502 --> 02:28:26,179 COLLAPSE AND DEATHS RELATES TO 2502 02:28:26,179 --> 02:28:30,517 THE MITRAL VALVE COLLAPSE. 2503 02:28:30,517 --> 02:28:31,885 MAYBE A TRIPLE. 2504 02:28:31,885 --> 02:28:35,889 >> WHAT IS HEARD TO UNDERSTAND 2505 02:28:35,889 --> 02:28:38,592 IF THE SPECIFIC GENE CAUSES 2506 02:28:38,592 --> 02:28:41,328 PROLAPSE IN CARDIOMYOPATHY OR 2507 02:28:41,328 --> 02:28:45,065 WE'RE JUST PICKING UP THE 2508 02:28:45,065 --> 02:28:45,999 CARDIOMYOPATHY GENES. 2509 02:28:45,999 --> 02:28:47,934 IN THE CLINICAL WORLD THE 2510 02:28:47,934 --> 02:28:53,240 CLINICAL PANELS CONTAIN THE 2511 02:28:53,240 --> 02:28:58,945 GENES AND DON'T HAVE OF A 2512 02:28:58,945 --> 02:29:00,413 PROLAPSED GENE AND AT THE 2513 02:29:00,413 --> 02:29:05,218 MECHANISTIC LEVEL. 2514 02:29:05,218 --> 02:29:08,455 HOW CAN ONE PARTICULAR GENE AND 2515 02:29:08,455 --> 02:29:12,425 WHAT IS INVOLVED IN CELL TO CELL 2516 02:29:12,425 --> 02:29:15,328 COMMUNICATION AND HOW CAN IT 2517 02:29:15,328 --> 02:29:23,103 CAUSE THIS MAYBE CHIP CAN TELL 2518 02:29:23,103 --> 02:29:26,172 IN MORE DETAIL. 2519 02:29:26,172 --> 02:29:31,411 >> SOME ARE ASSOCIATED WITH 2520 02:29:31,411 --> 02:29:32,412 CARDIOMYOPATHY. 2521 02:29:32,412 --> 02:29:36,416 DID YOU FIND ANY LINK TO THOSE 2522 02:29:36,416 --> 02:29:46,926 GENES MENTIONED IN THE PAPER? 2523 02:29:56,936 --> 02:29:58,204 >> IN THE CARDIOMYOPATHY YOU'RE 2524 02:29:58,204 --> 02:30:00,940 MAKING UP SEVERE CASES NOT 2525 02:30:00,940 --> 02:30:03,643 REALLY FOCUSSING ON ARRHYTHMIC 2526 02:30:03,643 --> 02:30:05,045 CASES. 2527 02:30:05,045 --> 02:30:08,882 WE'RE MISSING A LARGE SCALE 2528 02:30:08,882 --> 02:30:09,516 ARRHYTHMIC FOCUS INVESTIGATION 2529 02:30:09,516 --> 02:30:15,422 TO KIND OF SORT OUT THE TWO AND 2530 02:30:15,422 --> 02:30:19,025 COMPARING MVP THAT'S NOT 2531 02:30:19,025 --> 02:30:21,428 ARRHYTHMIC AND WHICH ARE AND 2532 02:30:21,428 --> 02:30:23,930 SORT OUT WHICH ARE CAUSING THE 2533 02:30:23,930 --> 02:30:34,407 CARDIOMYOPATHY AND PROLAPSE. 2534 02:30:39,579 --> 02:30:47,754 THE TWO-PHASE APPROACH WILL MAKE 2535 02:30:47,754 --> 02:30:51,358 IT TO SORT OUT THE TRIGGER OR 2536 02:30:51,358 --> 02:30:54,160 INFLUENCE PLAY VARY FOR 2537 02:30:54,160 --> 02:30:57,430 NON-GENETIC FACTORS UNLESS ON 2538 02:30:57,430 --> 02:31:00,433 CHANNEL MYOPATHIES OR CHANNEL 2539 02:31:00,433 --> 02:31:02,402 GENES. 2540 02:31:02,402 --> 02:31:09,442 IT MAY BE INTERESTING TO 2541 02:31:09,442 --> 02:31:15,949 STRATIFY THE STRESS ON THE 2542 02:31:15,949 --> 02:31:20,420 MYOCARDIUM AND IF IT CAN BE 2543 02:31:20,420 --> 02:31:26,426 DONE, WE'LL DO IT. 2544 02:31:26,426 --> 02:31:28,061 >> ABOUT WHAT IF THEY ONLY HAVE 2545 02:31:28,061 --> 02:31:28,461 ONE HIT? 2546 02:31:28,461 --> 02:31:31,331 DOES IT PUT IT INTO A LOWER RISK 2547 02:31:31,331 --> 02:31:31,598 CATEGORY? 2548 02:31:31,598 --> 02:31:33,433 THAT WOULD BE INTERESTING TO SEE 2549 02:31:33,433 --> 02:31:42,942 IN THE FUTURE. 2550 02:31:42,942 --> 02:31:47,280 >> OR ONE GENE VERSUS MULTIPLE 2551 02:31:47,280 --> 02:31:51,217 GENES. 2552 02:31:51,217 --> 02:31:53,787 >> TO HAVE AN IDEA WHAT IS RISK 2553 02:31:53,787 --> 02:31:57,157 AND NOT RISK AND WHAT COMES OUT 2554 02:31:57,157 --> 02:31:58,191 OF WHAT YOU'RE SAYING. 2555 02:31:58,191 --> 02:31:59,826 >> FOR SURE. 2556 02:31:59,826 --> 02:32:05,465 >> FRANCESSCA MENTIONED THE 2557 02:32:05,465 --> 02:32:07,066 PROSPECT OF CHUCK NORRIS GIVING 2558 02:32:07,066 --> 02:32:16,309 US INFORMATION BUT -- CHIP NOR 2559 02:32:16,309 --> 02:32:18,945 IS GIVING US ENFORCEMENT. 2560 02:32:18,945 --> 02:32:27,887 NEXT IS NABILA BOUATIA-NAJI. 2561 02:32:27,887 --> 02:32:29,456 >> THANK YOU FOR ALLOWING ME TO 2562 02:32:29,456 --> 02:32:35,462 SHARE WITH YOU OF THE THE 2563 02:32:35,462 --> 02:32:40,967 WORKSHOP ON THE DATA ON WORKSHOP 2564 02:32:40,967 --> 02:32:43,803 AND THERE'LL BE AN OVERLAP WITH 2565 02:32:43,803 --> 02:32:44,437 THE WORK I SHARED WITH SOME OF 2566 02:32:44,437 --> 02:32:54,514 YOU. 2567 02:33:24,110 --> 02:33:29,282 JD WORKING ON CASES AND WHY THE 2568 02:33:29,282 --> 02:33:34,787 GENETIC RESULTS WERE ENRICHED IN 2569 02:33:34,787 --> 02:33:41,961 SURGERY CASES BUT AND YOU HAVE 2570 02:33:41,961 --> 02:33:44,163 LIMITATIONS IN GENETIC STUDIES 2571 02:33:44,163 --> 02:33:45,431 YOU HAVE BIG NUMBERS AND LARGE 2572 02:33:45,431 --> 02:33:47,700 PANELISTS TO HAVE THE SITUATION 2573 02:33:47,700 --> 02:33:53,072 OF GETTING CONTROLS AND SUPER 2574 02:33:53,072 --> 02:34:03,783 CLOSE PHENOTYPES AND HARD TO GET 2575 02:34:13,226 --> 02:34:14,327 FAMILIES FOR SPECIFIC PHENOTYPES 2576 02:34:14,327 --> 02:34:16,296 AND THE SPORADIC SITUATION DOES 2577 02:34:16,296 --> 02:34:20,433 NOT FIT INTO WHAT STUDY UP LARGE 2578 02:34:20,433 --> 02:34:30,577 PANELS. 2579 02:34:35,582 --> 02:34:40,019 AND THIS WAS A SUCCESS STORY BUT 2580 02:34:40,019 --> 02:34:42,388 MANY MANY ATTEMPTS WERE NOT 2581 02:34:42,388 --> 02:34:44,424 SUCCESSFUL AS MOST THE PEOPLE OF 2582 02:34:44,424 --> 02:34:46,492 THE CALL WERE AND RECENTLY THE 2583 02:34:46,492 --> 02:34:53,900 WORK WE CONDUCTED ALL TOGETHER 2584 02:34:53,900 --> 02:34:59,272 INVOLVING MANY GENETICS OF MVP 2585 02:34:59,272 --> 02:35:09,782 PRESENT TODAY AND THE PROBLEM 2586 02:35:10,850 --> 02:35:12,418 WHERE GENETICS AND PROLAPSE AND 2587 02:35:12,418 --> 02:35:14,921 THIS IS SOMETHING I'M HAPPY I 2588 02:35:14,921 --> 02:35:16,422 WAS INVOLVED IN THE 2589 02:35:16,422 --> 02:35:18,024 DEMONSTRATION THAT THERE IS 2590 02:35:18,024 --> 02:35:19,959 ACTUALLY A COMPLEX GENETIC 2591 02:35:19,959 --> 02:35:20,960 FEATURE OF THIS DISEASE. 2592 02:35:20,960 --> 02:35:27,433 IT'S HIGHLY POLY GENIC AND 2593 02:35:27,433 --> 02:35:29,969 THERE'S AN INFLUENCE COULD BE 2594 02:35:29,969 --> 02:35:31,437 LIFESTYLE OR MECHANICAL BEATING 2595 02:35:31,437 --> 02:35:34,774 OF THE HEART OR LIFESTYLE. 2596 02:35:34,774 --> 02:35:36,809 THEY'RE ALL TRIGGERS THAT 2597 02:35:36,809 --> 02:35:38,811 INTERACT WITH THE GENETIC 2598 02:35:38,811 --> 02:35:40,246 SUSCEPTIBILITY AND NOT TALKING 2599 02:35:40,246 --> 02:35:42,415 ABOUT CAUSALITY AND 2600 02:35:42,415 --> 02:35:43,149 SUSCEPTIBILITY WITH TINY 2601 02:35:43,149 --> 02:35:44,417 INDIVIDUAL AFFECTS. 2602 02:35:44,417 --> 02:35:46,819 AND WE DON'T HAVE A FULL PICTURE 2603 02:35:46,819 --> 02:35:47,153 YET. 2604 02:35:47,153 --> 02:35:51,324 WE HAVE ATTEMPTS TO IMPROVE OUR 2605 02:35:51,324 --> 02:35:55,595 IMAGE OF THE PUZZLE AND IT'S BIG 2606 02:35:55,595 --> 02:36:01,067 FOR MOST CARDIOVASCULAR 2607 02:36:01,067 --> 02:36:01,334 DISEASES. 2608 02:36:01,334 --> 02:36:04,404 I WAS INVOLVED IN APPLYING 2609 02:36:04,404 --> 02:36:08,508 GENETIC ASSOCIATION STUDIES TO 2610 02:36:08,508 --> 02:36:11,010 UNDERSTAND THE GENETIC BASES AND 2611 02:36:11,010 --> 02:36:13,680 THERE'S PROOF THERE'S A POLY 2612 02:36:13,680 --> 02:36:16,549 GENIC NATURE OF THE DISEASE. 2613 02:36:16,549 --> 02:36:19,485 WE TAKE A NORMAL SAMPLE OF 2614 02:36:19,485 --> 02:36:22,789 POPULATION BASE AND A DISEASE 2615 02:36:22,789 --> 02:36:24,390 SAMPLE AND WE COMPARE THE 2616 02:36:24,390 --> 02:36:26,993 GENETIC INFORMATION THAT WE 2617 02:36:26,993 --> 02:36:28,194 EXTRACT SOMETIMES BY GENOTYPING 2618 02:36:28,194 --> 02:36:30,163 MORE AND MORE BY SEQUENCING OF 2619 02:36:30,163 --> 02:36:35,268 THE DATA OF THE INDIVIDUALS AND 2620 02:36:35,268 --> 02:36:37,203 THEN WE AND DISTINGUISH BETWEEN 2621 02:36:37,203 --> 02:36:39,605 WHAT ARE THE GENETIC POSITIONS 2622 02:36:39,605 --> 02:36:41,708 WHERE WE SEE A DIFFERENCE IN 2623 02:36:41,708 --> 02:36:44,410 FREQUENCY AND BETWEEN THE CASES 2624 02:36:44,410 --> 02:36:49,182 AND THE CONTROLS. 2625 02:36:49,649 --> 02:36:50,983 THIS APPROACH WAS APPLIED IN THE 2626 02:36:50,983 --> 02:36:51,317 RECENT YEARS. 2627 02:36:51,317 --> 02:36:53,586 WE'RE GOING TO CELEBRATE THE 10 2628 02:36:53,586 --> 02:36:59,125 YEARS OF OUR PAPERS IN 2015 WITH 2629 02:36:59,125 --> 02:37:03,129 OTHERS AND THIS WAS PUBLISHED 10 2630 02:37:03,129 --> 02:37:06,332 YEARS AGO WHERE WE DESCRIBE THE 2631 02:37:06,332 --> 02:37:08,501 LOCI AND THIS WAS A SMALL COHORT 2632 02:37:08,501 --> 02:37:11,704 BUT WE HAD ACTUALLY TWO 2633 02:37:11,704 --> 02:37:13,840 DISCOVERY COHORTS WHERE WE GOT 2634 02:37:13,840 --> 02:37:16,242 THESE SURGERY ENRICHMENT IN THE 2635 02:37:16,242 --> 02:37:18,444 SAMPLES AND THAT'S DEFINITELY IN 2636 02:37:18,444 --> 02:37:20,413 MY OPINION THE REASON WHY WE 2637 02:37:20,413 --> 02:37:22,849 WERE SUCCESSFUL DESPITE THE VERY 2638 02:37:22,849 --> 02:37:25,151 SMALL NUMBERS FOR THE DISCOVERY 2639 02:37:25,151 --> 02:37:30,723 OF 1500 INDIVIDUALS. 2640 02:37:30,723 --> 02:37:41,267 RECENTLY WE AND HERE WE GO THIS 2641 02:37:54,947 --> 02:37:59,085 IS WHAT MAY BE PRESENTED YEARS 2642 02:37:59,085 --> 02:37:59,352 AGO. 2643 02:37:59,352 --> 02:38:03,589 THE WORKSHOP AND THE UPDATE FROM 2644 02:38:03,589 --> 02:38:11,597 A MORE RECENT EFFORTS. 2645 02:38:11,597 --> 02:38:17,203 THIS IS AN INITIATIVE LED BY THE 2646 02:38:17,203 --> 02:38:20,039 BROAD AND THEY ARE WERE ABLE TO 2647 02:38:20,039 --> 02:38:26,646 COLLECT A MUCH LARGER SAMPLE OF 2648 02:38:26,646 --> 02:38:27,280 CASES OF MITRAL VALVE PROLAPSE 2649 02:38:27,280 --> 02:38:30,650 AND THE GENETICS CONSORTIUM OF 2650 02:38:30,650 --> 02:38:36,055 MVP AND MADE RAY HUGE EFFORT TO 2651 02:38:36,055 --> 02:38:39,425 USE ACD TO COLLECT MORE IN 2652 02:38:39,425 --> 02:38:40,193 INDIVIDUALS AFFECTED AND 2653 02:38:40,193 --> 02:38:41,627 INCREASE FROM 5,000 TO 19,000 2654 02:38:41,627 --> 02:38:42,995 CASES RIGHT NOW. 2655 02:38:42,995 --> 02:38:48,634 SO THE IDEA WAS WAS TO LEVERAGE 2656 02:38:48,634 --> 02:38:50,303 CONTINENTAL GENETIC DATA AND 2657 02:38:50,303 --> 02:38:52,972 U.S.-BASED COHORT TO PERFORM THE 2658 02:38:52,972 --> 02:38:55,474 LARGEST U.S. MVP AND THE 2659 02:38:55,474 --> 02:38:57,610 MOTIVATION IS WE SEE LOCI WE 2660 02:38:57,610 --> 02:39:00,112 KNOW IS NOT COVERED AND WE ALSO 2661 02:39:00,112 --> 02:39:02,248 WANTED TO PRIORITIZE CAUSE OF 2662 02:39:02,248 --> 02:39:05,818 GENES AND USING MORE 2663 02:39:05,818 --> 02:39:06,352 SOPHISTICATED ROTATION TO 2664 02:39:06,352 --> 02:39:08,387 UNDERSTAND WHAT ARE THE PATHWAYS 2665 02:39:08,387 --> 02:39:11,490 THAT ARE COVERED BY THOSE 2666 02:39:11,490 --> 02:39:14,193 GENETIC RISK GENES OF LVP. 2667 02:39:14,193 --> 02:39:16,095 THIS IS A DESCRIPTION OF THE 2668 02:39:16,095 --> 02:39:18,497 COMPOSITION. 2669 02:39:18,497 --> 02:39:21,300 ALL THESE LARGE STUDIES ARE 2670 02:39:21,300 --> 02:39:24,437 BASED ON THE PROGRAM AND THE 2671 02:39:24,437 --> 02:39:25,838 STUDIES HAVE MORE CONTROLS THAN 2672 02:39:25,838 --> 02:39:26,539 CASES. 2673 02:39:26,539 --> 02:39:30,209 WE MAKE SURE IT'S NOT 2674 02:39:30,209 --> 02:39:31,177 INTRODUCING VIRUS USING 2675 02:39:31,177 --> 02:39:32,845 STATISTICAL TRICKS. 2676 02:39:32,845 --> 02:39:35,915 THE ANCESTRY IS PREDOMINANTLY 2677 02:39:35,915 --> 02:39:36,716 EUROPEAN AND ONE OF THE 2678 02:39:36,716 --> 02:39:39,318 LIMITATIONS OF THE STUDY AND HOW 2679 02:39:39,318 --> 02:39:40,419 COMPLICATED IT IS TO GET LARGE 2680 02:39:40,419 --> 02:39:43,189 AND WELL POWERED NON-EUROPEAN 2681 02:39:43,189 --> 02:39:45,625 POPULATIONS THAT STILL HAVE A 2682 02:39:45,625 --> 02:39:46,659 SMALL FRACTION OF AFRICAN 2683 02:39:46,659 --> 02:39:49,929 AMERICAN AND HISPANIC BUT IT'S 2684 02:39:49,929 --> 02:39:50,997 ONLY THE ANCESTRY BASE IN THE 2685 02:39:50,997 --> 02:39:52,031 U.S. WHICH IS DIFFERENT FROM 2686 02:39:52,031 --> 02:39:58,871 WHAT WOULD BE HAPPENING IN 2687 02:39:58,871 --> 02:40:00,940 CONTINENTS AND THE PROGRAM WHERE 2688 02:40:00,940 --> 02:40:03,609 IT IS PREDOMINANTLY MALE 2689 02:40:03,609 --> 02:40:08,948 POPULATION. 2690 02:40:08,948 --> 02:40:19,392 THIS IS THE IMAGE WE HAVE. 2691 02:40:19,392 --> 02:40:25,197 AND THERE'S A NEW COHORT AND WE 2692 02:40:25,197 --> 02:40:29,402 ARE 74 LOCI AND THESE ARE MOSTLY 2693 02:40:29,402 --> 02:40:31,270 NOVEL. 2694 02:40:31,270 --> 02:40:33,572 AGAIN IT THIS JUST SHOWS THE 2695 02:40:33,572 --> 02:40:35,408 OBSESSION TO GET LARGER AND 2696 02:40:35,408 --> 02:40:38,444 LARGER COHORTS IT'S VERY 2697 02:40:38,444 --> 02:40:43,549 EFFICIENT TO RECOVER THE 2698 02:40:43,549 --> 02:40:46,118 VARIANTS WHICH IDENTIFY THE GWAS 2699 02:40:46,118 --> 02:40:48,421 AND HERE YOU COVER MORE 2700 02:40:48,421 --> 02:40:51,190 MECHANISMS AND GENETIC RISK BY 2701 02:40:51,190 --> 02:40:54,193 INCREASING THE SAMPLES YOU 2702 02:40:54,193 --> 02:40:56,896 OVERCOME THE HETEROGENEITY OF 2703 02:40:56,896 --> 02:41:00,666 THE DISEASE THOUGH YOU NEVER 2704 02:41:00,666 --> 02:41:01,801 COMPLETELY COVER THAT ISSUE 2705 02:41:01,801 --> 02:41:03,602 THROUGH THIS KIND OF DESIGN BUT 2706 02:41:03,602 --> 02:41:06,772 STILL IT GIVES YOU A LITTLE BIT 2707 02:41:06,772 --> 02:41:08,407 MORE STATISTICAL POWER TO DETECT 2708 02:41:08,407 --> 02:41:10,443 MORE LOCI THIS IS THE CASE HERE. 2709 02:41:10,443 --> 02:41:14,013 IT'S IMPRESSIVE EVERY TIME I RUN 2710 02:41:14,013 --> 02:41:15,881 A GWAS I'M SURPRISED HOW MUCH 2711 02:41:15,881 --> 02:41:18,517 RISK AND SIGNALS WE CAN SEE FROM 2712 02:41:18,517 --> 02:41:20,052 THOSE THAT SUPPORT THE POLY 2713 02:41:20,052 --> 02:41:27,326 GENETIC NATURE OF THE DISEASE. 2714 02:41:27,326 --> 02:41:28,427 SO, NOW ONE OF THE VERY 2715 02:41:28,427 --> 02:41:29,462 IMPORTANT QUESTIONS WE WANT TO 2716 02:41:29,462 --> 02:41:32,398 ADDRESS ESPECIALLY IN MY LAB IS 2717 02:41:32,398 --> 02:41:38,137 WE WANT TO REALLY KNOW WHAT IS 2718 02:41:38,137 --> 02:41:39,538 GETTING BEHIND THE STATISTICAL 2719 02:41:39,538 --> 02:41:41,140 ASSOCIATION AGAIN FROM GENETICS 2720 02:41:41,140 --> 02:41:43,042 TO THE BIOLOGICAL IMPACT OF THE 2721 02:41:43,042 --> 02:41:43,309 VARIANTS. 2722 02:41:43,309 --> 02:41:49,849 SO THIS IS SOMETHING WE CAN DO 2723 02:41:49,849 --> 02:41:53,152 AT A SMALL SCALE. 2724 02:41:53,152 --> 02:41:58,924 AND IN ONE OF OUR RECENT WORK 2725 02:41:58,924 --> 02:42:01,794 WE'RE ABLE TO USE THE GENETIC 2726 02:42:01,794 --> 02:42:03,562 INFORMATION TO REFINE THE SIGNAL 2727 02:42:03,562 --> 02:42:07,299 IN ONE AND IMPORTANT LOCUS 2728 02:42:07,299 --> 02:42:11,837 IDENTIFIED IN THE INITIAL STUDY 2729 02:42:11,837 --> 02:42:17,176 AS CAUSING THIS IN ZEBRAFISH AND 2730 02:42:17,176 --> 02:42:18,144 MORPHOLOGY MITRAL VALVE IN MOUSE 2731 02:42:18,144 --> 02:42:21,614 AND APPLY A CHROMATIN 2732 02:42:21,614 --> 02:42:23,182 INTERACTION EXPERIMENT. 2733 02:42:23,182 --> 02:42:25,117 THAT MEANS BECAUSE THE VARIANT 2734 02:42:25,117 --> 02:42:27,653 FOR REGULATION WAS FAR AWAY WE 2735 02:42:27,653 --> 02:42:30,156 WERE ABLE TO PROVE THERE WAS AN 2736 02:42:30,156 --> 02:42:32,425 INTERACTION BETWEEN THE REGION 2737 02:42:32,425 --> 02:42:35,361 AN PROMOTER AND ALSO IN VITRO 2738 02:42:35,361 --> 02:42:37,663 ANALYSIS TO DEMONSTRATE THE ROLE 2739 02:42:37,663 --> 02:42:40,299 OF THIS VARIANT IN THE ACTIVITY 2740 02:42:40,299 --> 02:42:44,437 OF INDIVIDUAL ACTIVITY USING 2741 02:42:44,437 --> 02:42:49,108 REPORTER ASSAYS. 2742 02:42:49,108 --> 02:42:51,644 AND MOST INTERESTING IS PROVIDE 2743 02:42:51,644 --> 02:43:02,188 AN OPEN CHROMATIN MATCH AND AND 2744 02:43:04,090 --> 02:43:05,291 THIS WAS INTERESTING TO GENERATE 2745 02:43:05,291 --> 02:43:09,628 AND WE GET INTEREST IN LESSONS 2746 02:43:09,628 --> 02:43:11,297 LEARNED FROM THIS EXPERIMENT. 2747 02:43:11,297 --> 02:43:13,799 FIRST WE USED IT TO ANNOTATE OUR 2748 02:43:13,799 --> 02:43:21,307 GWAS RESULTS THAT WAS MORE 2749 02:43:21,307 --> 02:43:29,115 DESCRIBING MORE LOCI. 2750 02:43:29,115 --> 02:43:31,383 >> THIS IS USING DATA THE 2751 02:43:31,383 --> 02:43:34,386 UPDATED GWAS WE CONFIRMED THERE 2752 02:43:34,386 --> 02:43:37,756 IS AN IMPORTANT ROLE OF 2753 02:43:37,756 --> 02:43:40,192 ENRICHMENT IN TERMS OF FOLD IN 2754 02:43:40,192 --> 02:43:45,231 THE NORMAL AND YOU'LL NOTICE THE 2755 02:43:45,231 --> 02:43:47,566 NORMAL HAS A HUNDREDFOLD 2756 02:43:47,566 --> 02:43:51,303 ENRICHMENT PROBABLY BECAUSE YOU 2757 02:43:51,303 --> 02:43:56,275 HAVE MORE CELLS AND METRICS AND 2758 02:43:56,275 --> 02:43:57,610 FIBROSIS THAT DIMINISH THE 2759 02:43:57,610 --> 02:44:00,412 CHANCES TO DETECT ENRICHMENT THE 2760 02:44:00,412 --> 02:44:05,217 BUT ALSO THERE IS THE ENRICHMENT 2761 02:44:05,217 --> 02:44:07,753 FOR THE VENTRICLE. 2762 02:44:07,753 --> 02:44:08,988 WE SEE CONSISTENTLY AROUND OUR 2763 02:44:08,988 --> 02:44:10,689 ANALYSIS EACH TIME WE DO 2764 02:44:10,689 --> 02:44:11,290 ENRICHMENT. 2765 02:44:11,290 --> 02:44:13,626 SO THE EXPERIMENTS JUST GIVE YOU 2766 02:44:13,626 --> 02:44:16,428 A COMPARISON BETWEEN THE 2767 02:44:16,428 --> 02:44:19,331 POSITION ASSOCIATED WITH MVP AND 2768 02:44:19,331 --> 02:44:22,368 WHERE THEY ARE COMPARED TO OPEN 2769 02:44:22,368 --> 02:44:23,969 CHROMATIN AND THE TISSUE BECAUSE 2770 02:44:23,969 --> 02:44:25,771 OPEN CHROMATIN IS SPECIFIC TO 2771 02:44:25,771 --> 02:44:26,005 TISSUES. 2772 02:44:26,005 --> 02:44:28,440 IT MAKES SENSE TO WHAT IS 2773 02:44:28,440 --> 02:44:28,741 HAPPENING. 2774 02:44:28,741 --> 02:44:33,746 SOMETIMES IT'S IMPORTANT FOR ALL 2775 02:44:33,746 --> 02:44:36,182 TISSUES BECAUSE IT'S UBIQUITOUS 2776 02:44:36,182 --> 02:44:38,918 GENE BUT SOMETIMES YOU CAN SEE 2777 02:44:38,918 --> 02:44:43,889 WHAT IS HAPPENING IN THE HEART 2778 02:44:43,889 --> 02:44:45,658 AND ALSO IN THE MITRAL VALVE 2779 02:44:45,658 --> 02:44:54,366 TISSUE. 2780 02:44:54,366 --> 02:45:00,439 SHE PERFORMED AN INTEGRATION OF 2781 02:45:00,439 --> 02:45:04,777 THE GWAS INTO SINGLE CELL DATA 2782 02:45:04,777 --> 02:45:13,719 AND MOST THE VARIANTS ASSOCIATED 2783 02:45:13,719 --> 02:45:17,723 WITH MVP HAVE EXPRESSION IN 2784 02:45:17,723 --> 02:45:20,526 CELLS AND MYOFIBROBLASTS BUT 2785 02:45:20,526 --> 02:45:23,362 NOTHING IS HAPPENING FOR THE 2786 02:45:23,362 --> 02:45:26,532 ENDOTHELIAL CELLS WHICH IS 2787 02:45:26,532 --> 02:45:29,001 INTERESTING TO KNOW AND WE NEED 2788 02:45:29,001 --> 02:45:31,470 TO CONFIRM IT DOESN'T MEAN THE 2789 02:45:31,470 --> 02:45:33,672 CELL TYPE IS NOT IMPORTANT BUT 2790 02:45:33,672 --> 02:45:35,507 THE MODIFICATION WE SEE ARE 2791 02:45:35,507 --> 02:45:36,442 PREDOMINANTLY DRIVEN BY WHAT IS 2792 02:45:36,442 --> 02:45:46,885 HAPPENING WITH THE PEAKS. 2793 02:45:51,357 --> 02:45:53,025 AND YOU MAY HAVE CANDIDATE GENES 2794 02:45:53,025 --> 02:45:55,027 AROUND THE SIGNAL AND ONE OF THE 2795 02:45:55,027 --> 02:45:56,595 MOST IMPORTANT QUESTIONS YOU 2796 02:45:56,595 --> 02:46:01,533 WANT TO ANSWER IS THE LIKELY 2797 02:46:01,533 --> 02:46:03,702 GENE TO BE DRAWN DRAWING THE 2798 02:46:03,702 --> 02:46:08,641 BIOLOGICAL IMPACT MUCH THE 2799 02:46:08,641 --> 02:46:13,512 ASSOCIATION. 2800 02:46:13,512 --> 02:46:16,382 AND SOMETIMES THE ASSOCIATED 2801 02:46:16,382 --> 02:46:17,916 VARIANT IS A COMBINANT STILL 2802 02:46:17,916 --> 02:46:19,985 CODED SO WHEN THE GENE HAS 2803 02:46:19,985 --> 02:46:21,620 VARIATION WE PRIORITIZE THAT 2804 02:46:21,620 --> 02:46:23,555 GENE AND SOMETIMES IT'S THE 2805 02:46:23,555 --> 02:46:26,992 PROMOTER WHERE IT'S LOCATED. 2806 02:46:26,992 --> 02:46:29,395 SOMETIMES A CORALS WITH 2807 02:46:29,395 --> 02:46:32,865 EXPRESSION IN A CARDIAC TISSUE 2808 02:46:32,865 --> 02:46:33,699 OR RELEVANT TO THE CARDIAC 2809 02:46:33,699 --> 02:46:38,537 FUNCTION. 2810 02:46:38,537 --> 02:46:43,242 WE PRIORITIZE THE GENES BASED ON 2811 02:46:43,242 --> 02:46:45,678 ASSOCIATION AND CONFIRMATION 2812 02:46:45,678 --> 02:46:50,816 INFORMING FROM THE DATABASES IN 2813 02:46:50,816 --> 02:46:52,651 CARDIAC TISSUE AS WELL AND AT 2814 02:46:52,651 --> 02:46:55,387 THE END WE PRIORITIZE 60 ALMOST 2815 02:46:55,387 --> 02:47:05,397 70 GENES. 2816 02:47:05,397 --> 02:47:07,933 WE DID HALFWAY GENES TO SEE HOW 2817 02:47:07,933 --> 02:47:09,802 THEIR FITTING IN THE PATHWAYS WE 2818 02:47:09,802 --> 02:47:12,071 HAVE TWO MAIN GROUPS. 2819 02:47:12,071 --> 02:47:14,306 ONE RELATED TO EXTRA CELLULAR 2820 02:47:14,306 --> 02:47:16,442 MATRIX AND THE ONE YOU SEE IN 2821 02:47:16,442 --> 02:47:19,244 THE LEFT OF THE PATHWAY. 2822 02:47:19,244 --> 02:47:20,946 UNFORTUNATELY WE DON'T SEE 2823 02:47:20,946 --> 02:47:22,614 CLEARLY THE CONNECTED DIFFERENT 2824 02:47:22,614 --> 02:47:24,183 GENES BUT THAT'S PROBABLY DUE TO 2825 02:47:24,183 --> 02:47:26,418 THE CONVERSION INTO PDF AND YOU 2826 02:47:26,418 --> 02:47:30,022 HAVE ON THE OTHER HAND MANY 2827 02:47:30,022 --> 02:47:33,592 GENES RELATED TO INVOLVEMENT OR 2828 02:47:33,592 --> 02:47:37,529 CARDIOMYOPATHY GENES. 2829 02:47:37,529 --> 02:47:43,736 THIS HAS BEEN DONE AS SAYS BY 2830 02:47:43,736 --> 02:47:45,437 FRANCESSCA BUT WE HAVE GOOD 2831 02:47:45,437 --> 02:47:47,406 MORNING WORK BETWEEN MVP AND 2832 02:47:47,406 --> 02:47:56,448 MANY OTHER CARDIAC PHENOTYPES 2833 02:47:56,448 --> 02:48:06,892 ESPECIALLY CARDIOMYOPATHY. 2834 02:48:11,263 --> 02:48:14,900 SEE WHAT THE FIBROSIS ONSET AND 2835 02:48:14,900 --> 02:48:18,604 HERE IN THE GENES THIS IS ONE OF 2836 02:48:18,604 --> 02:48:22,808 THE IDEAS WITH FOLLOW-UP AND 2837 02:48:22,808 --> 02:48:24,810 SOME ARE LINKED OR ASSOCIATED 2838 02:48:24,810 --> 02:48:26,278 WITH ARRHYTHMIA GENES. 2839 02:48:26,278 --> 02:48:28,981 WHEN WE TAKE OFF A LARGE NUMBER 2840 02:48:28,981 --> 02:48:30,749 OF HETEROGENEOUS CASES BUT 2841 02:48:30,749 --> 02:48:34,219 INCREASING THE SAMPLES YOU START 2842 02:48:34,219 --> 02:48:36,588 TO DETECT DIFFERENT GENETIC RISK 2843 02:48:36,588 --> 02:48:38,824 FACTORS RELATED TO THE ASPECTS 2844 02:48:38,824 --> 02:48:43,495 OF MVP THOUGH WE COULD NOT HAVE 2845 02:48:43,495 --> 02:48:45,063 A MECHANISM HOW THIS WORKS IS 2846 02:48:45,063 --> 02:48:48,267 ALWAYS VERY DIFFICULT WHEN YOU 2847 02:48:48,267 --> 02:48:51,470 COME TO AN AGING OR PHENOTYPE 2848 02:48:51,470 --> 02:48:54,606 THAT DEVELOPS WITH AGE. 2849 02:48:54,606 --> 02:48:56,975 YOU CAN KNOW WHICH ONE COMES 2850 02:48:56,975 --> 02:48:59,945 FIRST AND THIS SOMETHING THAT 2851 02:48:59,945 --> 02:49:02,781 MAYBE NEEDS TO BE DISCOVERED 2852 02:49:02,781 --> 02:49:03,582 WITH OTHER METHODOLOGY. 2853 02:49:03,582 --> 02:49:05,417 AND THE FACT IT'S BEING 2854 02:49:05,417 --> 02:49:08,887 GENETICALLY ASSOCIATED THAT 2855 02:49:08,887 --> 02:49:11,356 MEANS YOU CAN ALSO HAVE THE 2856 02:49:11,356 --> 02:49:15,394 PHENOTYPING HAVE DIFFERENT 2857 02:49:15,394 --> 02:49:15,828 ORI 2858 02:49:15,828 --> 02:49:16,228 ORIGINS. 2859 02:49:16,228 --> 02:49:18,163 WHEN WE SEE DIFFERENT GENETIC 2860 02:49:18,163 --> 02:49:20,532 MECHANISMS THIS IS WHAT IT MEANS 2861 02:49:20,532 --> 02:49:22,401 BECAUSE IT'S MULTI-FACTORIAL AND 2862 02:49:22,401 --> 02:49:23,035 MAY HAVE REASONS DIFFERENT FROM 2863 02:49:23,035 --> 02:49:33,245 EACH OTHER. 2864 02:49:33,512 --> 02:49:36,448 THERE'S DIFFERENT RESOURCES FOR 2865 02:49:36,448 --> 02:49:39,718 STUDIES AND ALSO THE CASE 2866 02:49:39,718 --> 02:49:42,020 CONTROLS THAT HAS EFFORTS TO 2867 02:49:42,020 --> 02:49:43,689 COLLECT AND ANALYZE LARGER AND 2868 02:49:43,689 --> 02:49:46,024 BIGGER SAMPLES AND HELPS TO 2869 02:49:46,024 --> 02:49:47,993 COVER THE HETEROGENEITY OF THE 2870 02:49:47,993 --> 02:49:53,999 DISEASE AND THIS IS NOT ONLY FOR 2871 02:49:53,999 --> 02:49:55,534 MOST CARDIOVASCULAR DISEASES 2872 02:49:55,534 --> 02:49:59,037 WITH THIS PATTERN OF INHERITANCE 2873 02:49:59,037 --> 02:50:01,373 AND A HARD TIME TO TRANSLATE TO 2874 02:50:01,373 --> 02:50:06,178 BIOLOGY AND WE TRY TO ACQUIRE 2875 02:50:06,178 --> 02:50:08,514 MULTI-OMIC COMBINATIONS AND 2876 02:50:08,514 --> 02:50:10,382 USING COLLABORATION WITH CHIP 2877 02:50:10,382 --> 02:50:11,083 MOUSE TISSUE SOMETIMES AND 2878 02:50:11,083 --> 02:50:14,486 DIFFERENT RESOURCES TO TRY TO 2879 02:50:14,486 --> 02:50:19,191 INTEGRATE TOGETHER INTO A WAY TO 2880 02:50:19,191 --> 02:50:21,693 UNDERSTAND HOW THESE DIFFERENT 2881 02:50:21,693 --> 02:50:23,562 LITTLE DYSFUNCTION IN THE 2882 02:50:23,562 --> 02:50:25,464 GENETIC REGULATION IN PARTICULAR 2883 02:50:25,464 --> 02:50:27,533 CONTRIBUTING TO MVP ONSETS. 2884 02:50:27,533 --> 02:50:30,602 AND THE LAST SLIDE IS THE TAKE 2885 02:50:30,602 --> 02:50:33,105 HOME MESSAGES. 2886 02:50:33,105 --> 02:50:34,673 I'LL SUMMARIZE THAT MVP GENETICS 2887 02:50:34,673 --> 02:50:36,975 IS CHALLENGING DUE TO THE 2888 02:50:36,975 --> 02:50:37,609 COMPLEX PHENOTYPE AND GENETIC 2889 02:50:37,609 --> 02:50:41,413 MODEL AND THE INTEGRATION OF 2890 02:50:41,413 --> 02:50:44,283 MULTI-OMIC RESOURCES MAINLY GWAS 2891 02:50:44,283 --> 02:50:50,188 INFORMED THE BIOLOGY AND WE HAVE 2892 02:50:50,188 --> 02:50:56,461 MECHANISMS AND DATA FROM FAMILY 2893 02:50:56,461 --> 02:51:02,401 STUDIES AND FROM GWAS AND 2894 02:51:02,401 --> 02:51:04,202 LOOKING AT FIBROTIC PHENOTYPES 2895 02:51:04,202 --> 02:51:05,604 BUT NEED FUTURE EFFORTS TO 2896 02:51:05,604 --> 02:51:08,340 TRANSLATE THEM TO PREVENTIVE AND 2897 02:51:08,340 --> 02:51:08,674 THERAPEUTICS. 2898 02:51:08,674 --> 02:51:12,945 THAT WAS MY LAST SLIDE. 2899 02:51:12,945 --> 02:51:18,116 I'D LIKE TO THANK MY 2900 02:51:18,116 --> 02:51:22,254 COLLABORATORS FOR SHARING SLIDES 2901 02:51:22,254 --> 02:51:24,356 AND AND MANY OF THE CONSORTIUM 2902 02:51:24,356 --> 02:51:29,294 AND THANK YOU FOR YOUR 2903 02:51:29,294 --> 02:51:29,561 ATTENTION. 2904 02:51:29,561 --> 02:51:32,197 6: 2905 02:51:32,197 --> 02:51:33,532 >> DOES ANYONE HAVE COMMENTS OR 2906 02:51:33,532 --> 02:51:34,166 QUESTIONS ABOUT THIS PARTICULAR 2907 02:51:34,166 --> 02:51:44,276 TALK? 2908 02:51:57,756 --> 02:51:59,858 >> INFLUENCING THE QUALITY OF 2909 02:51:59,858 --> 02:52:01,460 THE GENOTYPING, DO YOU SCREEN 2910 02:52:01,460 --> 02:52:05,697 ALL THESE GENES THAT YOU HAVE 2911 02:52:05,697 --> 02:52:08,266 DISCOVERED BY IN A SENSE 2912 02:52:08,266 --> 02:52:10,168 MEDIOCRE PHENOTYPING TO SEE IF 2913 02:52:10,168 --> 02:52:13,639 THEY PRODUCE AN MVP OR DO YOU 2914 02:52:13,639 --> 02:52:19,945 PREFER TO HAVE BETTER DEFINED 2915 02:52:19,945 --> 02:52:20,779 PHENOTYPES LESS VARIATIONS AND 2916 02:52:20,779 --> 02:52:24,349 MORE TARGETED GENES TO ANALYZE 2917 02:52:24,349 --> 02:52:24,716 THEIR ROLE? 2918 02:52:24,716 --> 02:52:27,486 WHAT'S YOUR VIEW ON HOW TO 2919 02:52:27,486 --> 02:52:27,719 PROCEED? 2920 02:52:27,719 --> 02:52:32,090 DO WE NEED TO HAVE A CONSORTIUM 2921 02:52:32,090 --> 02:52:34,126 WHERE THE MVP IS WELL DEFINED BY 2922 02:52:34,126 --> 02:52:38,263 GOOD IMAGES OR WE DON'T CARE? 2923 02:52:38,263 --> 02:52:48,640 >> ALL THE APPROACHES HAVE AN 2924 02:52:48,640 --> 02:52:49,408 INPUT. 2925 02:52:49,408 --> 02:52:54,179 THIS HAS THE POWER TO DETECT 2926 02:52:54,179 --> 02:52:55,580 MORE LOCI AND COVERS MORE OF THE 2927 02:52:55,580 --> 02:52:58,684 DIFFERENT ASPECTS OF MVP. 2928 02:52:58,684 --> 02:53:02,754 I CAN DEFINITELY ENVISION A 2929 02:53:02,754 --> 02:53:03,555 SPECIFIC SPEENT WE WANT TO 2930 02:53:03,555 --> 02:53:05,190 INVESTIGATE IN THE CONTEXT OF 2931 02:53:05,190 --> 02:53:07,526 MVP AND AGAIN IF YOU HAVE A 2932 02:53:07,526 --> 02:53:11,229 LARGE SERIES OF PATIENTS WITH 2933 02:53:11,229 --> 02:53:12,964 FOR EXAMPLE MVP AND ARRHYTHMIA 2934 02:53:12,964 --> 02:53:16,201 AND CONDUCT THE GWAS YOU MAY 2935 02:53:16,201 --> 02:53:18,503 SPECIFICALLY FIND WHAT IS FOR 2936 02:53:18,503 --> 02:53:19,705 THIS PHENOTYPE IF YOU HAVE 2937 02:53:19,705 --> 02:53:20,605 LARGER SAMPLE. 2938 02:53:20,605 --> 02:53:22,641 THIS IS THE LIMITATION WHEN 2939 02:53:22,641 --> 02:53:25,310 YOU'RE DEALING WITH THIS COMPLEX 2940 02:53:25,310 --> 02:53:28,380 AND POLY GENIC DEFICIT YOU NEED 2941 02:53:28,380 --> 02:53:29,948 THE BIG NUMBERS BECAUSE THE 2942 02:53:29,948 --> 02:53:31,450 STATISTICAL POWER DOES NOT 2943 02:53:31,450 --> 02:53:33,518 FORGIVE YOU IF YOU PUT SMALLER 2944 02:53:33,518 --> 02:53:36,988 SAMPLES YOU WILL NOT HAVE 2945 02:53:36,988 --> 02:53:37,222 RESULTS. 2946 02:53:37,222 --> 02:53:42,928 EVEN IF THE PHENOTYPE IS VERY 2947 02:53:42,928 --> 02:53:44,596 PRECISE. 2948 02:53:44,596 --> 02:53:51,269 IF YOU GO FOR A BALANCE AND BOTH 2949 02:53:51,269 --> 02:53:56,441 APPROACHES GIVE AN INTEREST IN 2950 02:53:56,441 --> 02:54:06,752 AND A STEP AHEAD. 2951 02:54:08,653 --> 02:54:08,787 . 2952 02:54:08,787 --> 02:54:10,489 THE CHALLENGE OF THIS KIND OF 2953 02:54:10,489 --> 02:54:12,090 APPROACH IS WE HAVE GOT WE HAVE 2954 02:54:12,090 --> 02:54:16,294 TO GO BACK TO EACH OF THOSE 2955 02:54:16,294 --> 02:54:18,330 CONTRIBUTING COHORTS LEFT TO 2956 02:54:18,330 --> 02:54:23,769 DEVELOP ALMOST 30 CENTERS AND 2957 02:54:23,769 --> 02:54:24,803 STRATIFIED BEFORE DOING THE 2958 02:54:24,803 --> 02:54:26,938 ANALYSIS WHICH IS CHALLENGING. 2959 02:54:26,938 --> 02:54:29,107 THIS COULD AN EFFORT TO THE WORK 2960 02:54:29,107 --> 02:54:35,814 AND WE NEED TO PUSH INTO HAVING 2961 02:54:35,814 --> 02:54:41,153 A LARGE AND ANALYSIS DEFINITELY. 2962 02:54:41,153 --> 02:54:43,789 >> AND A QUICK QUESTION, 2963 02:54:43,789 --> 02:54:44,389 EXCELLENT TALK. 2964 02:54:44,389 --> 02:54:46,124 WHEN YOU WERE SHOWING THE DATA 2965 02:54:46,124 --> 02:54:49,761 ON THE RNA SEQUENCING WAS THIS 2966 02:54:49,761 --> 02:54:55,200 FROM THE TISSUE YOU WERE 2967 02:54:55,200 --> 02:55:05,577 PROCESSING OR SAMPLE. 2968 02:55:09,848 --> 02:55:11,082 >> YOU CAN HAVE INFORMING FROM 2969 02:55:11,082 --> 02:55:20,192 THAT AND THE PUBLICATION IS IN 2970 02:55:20,192 --> 02:55:21,293 CIRCULATION. 2971 02:55:21,293 --> 02:55:24,629 THERE WAS A HEALTHY MITRAL VALVE 2972 02:55:24,629 --> 02:55:28,200 AND THE SEQ THE ONE WE PERFORMED 2973 02:55:28,200 --> 02:55:30,302 IN THE LAB THAT WAS ALSO MITRAL 2974 02:55:30,302 --> 02:55:34,239 VALVE AND WE DID THIS IN NORMAL 2975 02:55:34,239 --> 02:55:34,472 AND -- 2976 02:55:34,472 --> 02:55:39,144 >> THANK YOU. 2977 02:55:39,144 --> 02:55:45,250 >> FANTASTIC SCIENCE, NABILA 2978 02:55:45,250 --> 02:55:47,552 YOU'VE BEEN SHEPHERD. 2979 02:55:47,552 --> 02:55:51,323 NOW THAT THERE'S A MULTIPLICITY 2980 02:55:51,323 --> 02:55:53,658 OF VARIANTS WITH MVP AT 2981 02:55:53,658 --> 02:55:55,327 DIFFERENT LEVELS HOW DO WE 2982 02:55:55,327 --> 02:55:56,461 TRANSLATE THIS TO POTENTIAL 2983 02:55:56,461 --> 02:55:57,696 MECHANISMS AND TREATMENTS FOR 2984 02:55:57,696 --> 02:55:59,698 PATIENTS? 2985 02:55:59,698 --> 02:56:01,066 >> THAT'S THE BIG QUESTION WE'D 2986 02:56:01,066 --> 02:56:02,667 LIKE TO MOVE FORWARD. 2987 02:56:02,667 --> 02:56:03,969 I JUST WANT TO EMPHASIZE THE 2988 02:56:03,969 --> 02:56:06,338 FACT THAT IT'S NOT BECAUSE YOU 2989 02:56:06,338 --> 02:56:10,442 FIND THE MECHANISM RECENTLY OR 2990 02:56:10,442 --> 02:56:11,476 GENE IT'S LESS IMPORTANT THAN 2991 02:56:11,476 --> 02:56:13,178 THE FIRST ONE IDENTIFIED. 2992 02:56:13,178 --> 02:56:15,513 THIS IS THE LIMITATION OF GWAS 2993 02:56:15,513 --> 02:56:19,618 IS JUST WE DIDN'T HAVE THE GOOD 2994 02:56:19,618 --> 02:56:20,285 CONFIGURATION STATISTICALLY TO 2995 02:56:20,285 --> 02:56:21,519 OBSERVE THE EFFECT OF THE NEW 2996 02:56:21,519 --> 02:56:26,491 SERIES OF GENES. 2997 02:56:26,491 --> 02:56:28,860 THE GOOD NEWS IS WE HAVE 2998 02:56:28,860 --> 02:56:30,528 CONSISTENTLY THE SAME MECHANISMS 2999 02:56:30,528 --> 02:56:38,103 WHICH IS ASSURING AND IN TERMS 3000 02:56:38,103 --> 02:56:40,972 OF HOW THIS COULD BE TRANSLATED 3001 02:56:40,972 --> 02:56:45,644 TO BIOLOGY. 3002 02:56:45,644 --> 02:56:49,881 WE HAVE TOO MANY GENES AND FOR 3003 02:56:49,881 --> 02:56:52,384 THE INDIVIDUAL ANALYSIS TO MAKE 3004 02:56:52,384 --> 02:56:56,454 SURE YOU HAVE THE RIGHT TARGET 3005 02:56:56,454 --> 02:56:58,890 GENE AND CAN DO CRISPR 3006 02:56:58,890 --> 02:56:59,391 INHIBITION METHODS. 3007 02:56:59,391 --> 02:57:03,161 WE CAN DO THAT AND END UP WITH 3008 02:57:03,161 --> 02:57:04,462 MORE PRECISE DESIGN DESIGNATION 3009 02:57:04,462 --> 02:57:08,867 OF WHAT IS THE CANDIDATE GENE. 3010 02:57:08,867 --> 02:57:11,937 FROM THERE TO TRY TO AND THEY 3011 02:57:11,937 --> 02:57:13,538 ARE RECOMMEND TO DO NETWORK 3012 02:57:13,538 --> 02:57:15,440 ANALYSIS OF THE GENES AND TAKE 3013 02:57:15,440 --> 02:57:20,445 MAYBE THE GENES THAT ARE MOSTLY 3014 02:57:20,445 --> 02:57:21,279 ESSENTIAL IN THE NETWORK. 3015 02:57:21,279 --> 02:57:23,715 THEY'LL MORE LIKELY TO BE 3016 02:57:23,715 --> 02:57:26,284 IMPORTANT AND YOU'LL BE ABLE TO 3017 02:57:26,284 --> 02:57:27,752 MAY BE TO CREATE A CONSEQUENCE 3018 02:57:27,752 --> 02:57:33,191 OF THIS MECHANISM SOMEHOW AND 3019 02:57:33,191 --> 02:57:37,028 FROM AN OVERVIEW I DID WHAT IS 3020 02:57:37,028 --> 02:57:40,432 THE BEST DRUG TARGET FROM GWAS 3021 02:57:40,432 --> 02:57:42,434 DATA IS PROBABLY A GENE 3022 02:57:42,434 --> 02:57:43,969 ESSENTIAL IN THE NETWORK BUT NOT 3023 02:57:43,969 --> 02:57:45,203 SO MUCH WE DON'T MAKE IT 3024 02:57:45,203 --> 02:57:48,873 DISAPPEAR AND AT THE SAME TIME 3025 02:57:48,873 --> 02:57:52,911 WE HAVE A MOLECULE TO AFFECT ITS 3026 02:57:52,911 --> 02:57:56,448 CRITERION AND GIVE THE MOST 3027 02:57:56,448 --> 02:58:00,085 LIKELY GENE. 3028 02:58:00,085 --> 02:58:01,386 SEAS IMAGINE TO WORK ON AND IT'S 3029 02:58:01,386 --> 02:58:03,922 IMPORTANT TO GET UPDATED GENETIC 3030 02:58:03,922 --> 02:58:05,790 EFFORTS BECAUSE IT GIVES YOU 3031 02:58:05,790 --> 02:58:09,728 MORE QUANED DA CANDIDATES AND T 3032 02:58:09,728 --> 02:58:12,430 TO FIGURE OUT WHAT IT MOST 3033 02:58:12,430 --> 02:58:12,998 INTERESTING TO BE TARGETED 3034 02:58:12,998 --> 02:58:15,400 THERAPY. 3035 02:58:15,400 --> 02:58:20,505 >> THAT'S A WONDERFUL VISION OF 3036 02:58:20,505 --> 02:58:23,274 THE FUTURE. 3037 02:58:23,274 --> 02:58:28,446 >> THE FINAL PRESENTATION IN 3038 02:58:28,446 --> 02:58:38,990 THIS PORTION IS CHIP NOR IS -- 3039 02:58:46,765 --> 02:58:46,931 NORRIS. 3040 02:58:46,931 --> 02:58:51,136 >> I'M A MERE SCIENTIST AND 3041 02:58:51,136 --> 02:58:52,370 INTERESTED TO SEE HOW YOU'RE 3042 02:58:52,370 --> 02:58:53,738 MAKING LIVES BETTER FOR THESE 3043 02:58:53,738 --> 02:58:54,572 PATIENTS. 3044 02:58:54,572 --> 02:58:57,642 INTEGRATION IS KEY TO 3045 02:58:57,642 --> 02:59:02,414 UNDERSTANDING MVP AND THE PI 3046 02:59:02,414 --> 02:59:03,982 FIBROSIS ASSOCIATED WITH THIS 3047 02:59:03,982 --> 02:59:07,152 AND WITHOUT THE INTEGRATION THE 3048 02:59:07,152 --> 02:59:12,357 POTENTIAL COULD BE LIMITED AND 3049 02:59:12,357 --> 02:59:14,325 HOW CAN WE DEVELOP THESE 3050 02:59:14,325 --> 02:59:17,662 PREDICTIVE TOOL TO TELL US 3051 02:59:17,662 --> 02:59:19,397 WHETHER PATIENTS IS READY FOR 3052 02:59:19,397 --> 02:59:19,631 SURGERY? 3053 02:59:19,631 --> 02:59:23,535 SO YOU HAVE TO INTEGRATE THE 3054 02:59:23,535 --> 02:59:26,905 MOLECULAR TOOLS, MOLECULAR 3055 02:59:26,905 --> 02:59:28,106 IMAGING AND THE CURRENT ECHO 3056 02:59:28,106 --> 02:59:32,444 BASE AND OTHER PHYSIOLOGICAL 3057 02:59:32,444 --> 02:59:34,245 MACHINES TO BE ABLE TO CAPTURE 3058 02:59:34,245 --> 02:59:36,581 HOW TO DEFINE THESE PATIENTS AND 3059 02:59:36,581 --> 02:59:39,717 KNOW WHICH ONES WILL BENEFIT 3060 02:59:39,717 --> 02:59:41,820 FROM EARLIER SURGERY. 3061 02:59:41,820 --> 02:59:45,623 SO I'M GOING TO TELL YOU A 3062 02:59:45,623 --> 02:59:47,592 LITTLE BIT ABOUT HOW WE SORT 3063 02:59:47,592 --> 02:59:49,527 OF -- WE WANT TOO UNDERSTAND THE 3064 02:59:49,527 --> 02:59:50,161 QUESTION OF WHY. 3065 02:59:50,161 --> 02:59:54,165 WHY DO PATIENTS DEVELOP THESE 3066 02:59:54,165 --> 02:59:56,000 FIBROTIC LESIONS. 3067 02:59:56,000 --> 02:59:57,735 WHAT'S THE MECHANISM BEHIND THEM 3068 02:59:57,735 --> 03:00:02,774 AND CAN THAT LEAD TO NOT ONLY 3069 03:00:02,774 --> 03:00:03,741 THERAPIES BUT MOLECULAR TOOLS 3070 03:00:03,741 --> 03:00:08,113 THAT CAN THEN BE APPLIED TO 3071 03:00:08,113 --> 03:00:10,849 FOLLOW THESE PATIENTS -- YOU 3072 03:00:10,849 --> 03:00:12,684 GUYS CAN FOLLOW THESE PATIENTS 3073 03:00:12,684 --> 03:00:15,286 AND ASSESS WHETHER THE CHANGES 3074 03:00:15,286 --> 03:00:17,789 IN THE FIBROTIC REGIONS ARE 3075 03:00:17,789 --> 03:00:20,458 PROGRESSING TO A REAL PATHOGENIC 3076 03:00:20,458 --> 03:00:30,535 REPLACEMENT FIBROTIC STATE. 3077 03:00:30,535 --> 03:00:33,905 WE'VE BELABORED THIS ALL MORNING 3078 03:00:33,905 --> 03:00:39,043 FROM PEOPLE MORE EXPERT THAN I 3079 03:00:39,043 --> 03:00:45,650 AM AND THIS IS A COLLABORATION 3080 03:00:45,650 --> 03:00:48,453 AND YOU CAN CLEARLY SEE 3081 03:00:48,453 --> 03:00:49,621 SIGNIFICANT REPLACEMENT FIBROSIS 3082 03:00:49,621 --> 03:00:54,859 IN BASAL MYOCARDIUM IN SOME 3083 03:00:54,859 --> 03:00:56,227 PATIENTS AND SOME ARE PROFOUND. 3084 03:00:56,227 --> 03:00:59,197 THIS IS A PRETTY SEVERE CASE BUT 3085 03:00:59,197 --> 03:01:00,632 THERE'S DIFFERENT LEVELS OF 3086 03:01:00,632 --> 03:01:03,434 FIBROSIS NOT JUST REPLACEMENT 3087 03:01:03,434 --> 03:01:04,035 BUT INTERSTITIAL FIBROSIS AS 3088 03:01:04,035 --> 03:01:14,145 WELL. 3089 03:01:17,549 --> 03:01:20,418 WITH THE WORK MUCH THE PREVIOUS 3090 03:01:20,418 --> 03:01:25,890 NETWORK LED BY DR. LAVIGNE, WE 3091 03:01:25,890 --> 03:01:32,030 ESTABLISHED THIS LARGE CORNER 3092 03:01:32,030 --> 03:01:34,566 SUM AND ONE OF THE POWERS OF THE 3093 03:01:34,566 --> 03:01:36,234 GENETICS IS NOT ONLY HAVING THE 3094 03:01:36,234 --> 03:01:39,737 DEVELOP TO DEVELOP THE POLY 3095 03:01:39,737 --> 03:01:42,874 GENETIC RISK SCORE OR A GENETIC 3096 03:01:42,874 --> 03:01:45,243 MAP OR ARCHITECTURE OF THE 3097 03:01:45,243 --> 03:01:46,878 DISEASE BUT ONE OF THE TRUE 3098 03:01:46,878 --> 03:01:52,116 POWERS IS TO ESTABLISH MODEL 3099 03:01:52,116 --> 03:02:02,660 SYSTEMS TO AND THIS IS A COMMON 3100 03:02:04,095 --> 03:02:07,899 STRATEGY PHYSICIANS INTEGRATE TO 3101 03:02:07,899 --> 03:02:10,668 MAKE POSITIVE BENEFIT FOR 3102 03:02:10,668 --> 03:02:11,035 PATIENTS. 3103 03:02:11,035 --> 03:02:13,905 ONE OF THE VERY FIRST THINGS WE 3104 03:02:13,905 --> 03:02:15,740 DID WHEN WE IDENTIFIED THE 3105 03:02:15,740 --> 03:02:22,680 MUTATION I BELIEVE THIS WAS 3106 03:02:22,680 --> 03:02:24,749 FRANCESCA'S FAMILY -- 3107 03:02:24,749 --> 03:02:25,750 >> IT WAS. 3108 03:02:25,750 --> 03:02:36,027 >> I THOUGHT SO. 3109 03:02:42,767 --> 03:02:46,938 WE MADE THE EXACT SAME MUTATIONS 3110 03:02:46,938 --> 03:02:50,375 AND PUT IT IN THE MOUSE AND 3111 03:02:50,375 --> 03:02:51,142 PUBLISHED THIS YEARS AGO AND 3112 03:02:51,142 --> 03:02:55,813 WITH A SINGLE MUTATION DEVELOPED 3113 03:02:55,813 --> 03:02:58,383 MITRAL VALVE PROLAPSE SEEN AND 3114 03:02:58,383 --> 03:03:08,926 QUANTIFIED BY ECHO CARDIOGRAPHY 3115 03:03:09,661 --> 03:03:14,499 AND SAW CHANGES IN PATIENT LTZ 3116 03:03:14,499 --> 03:03:16,134 WITH MVP. 3117 03:03:16,134 --> 03:03:19,804 THE YELLOW STAIN IS COLLAGEN A 3118 03:03:19,804 --> 03:03:24,442 PAN MARKER FOR FIBROSIS. 3119 03:03:24,442 --> 03:03:27,712 EARLY ON THERE'S LITTLE FIBROSIS 3120 03:03:27,712 --> 03:03:33,651 IN THE MICE AND PROGRESSIVELY 3121 03:03:33,651 --> 03:03:35,320 DEVELOPED AND THERE'S A TIME AND 3122 03:03:35,320 --> 03:03:41,826 TEMPORAL COMPONENT TO THE LV 3123 03:03:41,826 --> 03:03:52,136 MOLECULAR CHANGES. 3124 03:03:58,109 --> 03:04:01,713 AND THIS INDICATED THE POTENTIAL 3125 03:04:01,713 --> 03:04:04,048 ROLE FOR MECHANICAL FORCES FOR 3126 03:04:04,048 --> 03:04:05,350 REDUCTION IN MVP. 3127 03:04:05,350 --> 03:04:15,860 THIS IS A NON-ISCHEMIC EVENT. 3128 03:04:24,602 --> 03:04:27,739 AND HOW DO CELLS SENSE THIS AND 3129 03:04:27,739 --> 03:04:32,443 KNOW TO RESPOND. 3130 03:04:37,915 --> 03:04:37,915 6: 3131 03:04:40,351 --> 03:04:42,153 HOW DOES THIS EFFECT STRESS AND 3132 03:04:42,153 --> 03:04:43,054 DEVELOPED TOOLS AND METHODS TO 3133 03:04:43,054 --> 03:04:53,364 TRY TO STUDY THIS. 3134 03:05:00,071 --> 03:05:00,972 LINKING MECHANICAL STRESS TO 3135 03:05:00,972 --> 03:05:01,839 FIBROSIS WOULD BE IDENTIFIED AND 3136 03:05:01,839 --> 03:05:06,944 WE CAN IDENTIFY THE PATHWAYS BY 3137 03:05:06,944 --> 03:05:11,015 UNBIASSED PROFILING AND THE RISK 3138 03:05:11,015 --> 03:05:12,950 COULD LEAD TO LEAD TO NEW 3139 03:05:12,950 --> 03:05:14,786 OPPORTUNITIES AND TOOLS THAT 3140 03:05:14,786 --> 03:05:15,386 COULD POTENTIALLY HAVE USE IN 3141 03:05:15,386 --> 03:05:25,530 CLINIC. 3142 03:05:43,247 --> 03:05:47,318 AND THERE'S AN OPPORTUNITY FOR 3143 03:05:47,318 --> 03:05:52,457 NEW MECHANISTIC INSIGHT AND THE 3144 03:05:52,457 --> 03:05:54,859 CRUX OF THE EXPERIMENTS IN AN 3145 03:05:54,859 --> 03:05:57,428 UNBIASSED WAY IS TO LOOK AT 3146 03:05:57,428 --> 03:06:00,431 EVERYTHING THE CELLS ARE MAKING 3147 03:06:00,431 --> 03:06:05,803 BY RNA AND THE STATUS OF THE 3148 03:06:05,803 --> 03:06:07,305 CHROMATIN AND IDENTIFY 3149 03:06:07,305 --> 03:06:09,841 TRANSCRIPTION FACTORS THAT ARE 3150 03:06:09,841 --> 03:06:12,877 DIFFERENTIAL BETWEEN THE DISEASE 3151 03:06:12,877 --> 03:06:15,746 REGIONS AND THE FIBROTIC 3152 03:06:15,746 --> 03:06:15,980 REGIONS. 3153 03:06:15,980 --> 03:06:18,216 THIS COULD BE DONE WITHIN THE 3154 03:06:18,216 --> 03:06:20,084 SAME HEART OR HUMAN AS THE CASE 3155 03:06:20,084 --> 03:06:23,187 FOR SOME STUDIES WE HAVE GOING 3156 03:06:23,187 --> 03:06:24,155 ON NOW. 3157 03:06:24,155 --> 03:06:25,590 WE CAN GET PERSONALIZED MEDICINE 3158 03:06:25,590 --> 03:06:36,033 LEVEL DATA ON THE STUDIES. 3159 03:06:51,849 --> 03:07:02,293 AND A HUMOR -- HUMAN OR MOUSE 3160 03:07:03,861 --> 03:07:04,896 HEART AND WE LOOKED AT THE 3161 03:07:04,896 --> 03:07:08,099 SIGNAL AND IT'S LIKELY STRETCH 3162 03:07:08,099 --> 03:07:09,033 OR MECHANICAL CHANGE. 3163 03:07:09,033 --> 03:07:14,272 SO LET'S PUT THESE CELLS UNDER A 3164 03:07:14,272 --> 03:07:15,840 STRINGENT CRITERIA AND STRESS 3165 03:07:15,840 --> 03:07:19,243 AMOUNT AND SEE HOW THEY CHANGE 3166 03:07:19,243 --> 03:07:20,444 IN AN ACUTE MODEL. 3167 03:07:20,444 --> 03:07:24,949 THESE WERE ALL DONE IN CELL 3168 03:07:24,949 --> 03:07:25,182 CULTURE. 3169 03:07:25,182 --> 03:07:28,786 WE DID A MULTI-OMIC APPROACH AND 3170 03:07:28,786 --> 03:07:35,326 COLLECTED RNA SEQ DATA AND ATAC 3171 03:07:35,326 --> 03:07:41,065 SEQ DATA AND WE'LL TALK ABOUT 3172 03:07:41,065 --> 03:07:51,242 THAT MORE. 3173 03:07:54,545 --> 03:07:59,550 WE CAN INTEGRATE. 3174 03:07:59,550 --> 03:08:10,094 WE'RE ABLE TO PRIORITIZE AND WE 3175 03:08:11,495 --> 03:08:14,198 HAVE SITES PRIORITIZED WHERE 3176 03:08:14,198 --> 03:08:17,602 THEY ARE WERE OPEN OR CLOSED 3177 03:08:17,602 --> 03:08:20,204 CHANGED CHROMATIN STATUS AND 3178 03:08:20,204 --> 03:08:22,640 INTEGRATE THAT WITH THE RNA SEQ 3179 03:08:22,640 --> 03:08:24,108 PROFILES FOR SPECIFIC GENES. 3180 03:08:24,108 --> 03:08:28,446 THAT'S LIST IN THE CIRCLE PLOT 3181 03:08:28,446 --> 03:08:31,749 ON THE TOP. 3182 03:08:31,749 --> 03:08:34,385 MOST ARE IN TRONIC REGIONS 3183 03:08:34,385 --> 03:08:40,124 ANYONE TO BE REGULATORY REGIONS 3184 03:08:40,124 --> 03:08:42,159 AROUND FOLD CHANGES REPRESENTED 3185 03:08:42,159 --> 03:08:45,830 WITH LOG VALUES DOWN BELOW. 3186 03:08:45,830 --> 03:08:48,199 SO FROM THIS WHAT DOES THIS TELL 3187 03:08:48,199 --> 03:08:48,432 US? 3188 03:08:48,432 --> 03:08:51,435 THE CELLS ARE DYNAMIC. 3189 03:08:51,435 --> 03:08:56,240 AND THESE ARE GENERALLY 3190 03:08:56,240 --> 03:08:58,175 QUIESCENT CELLS AND ABLE TO 3191 03:08:58,175 --> 03:09:00,177 RESPOND PROFOUNDLY AND RAPIDLY 3192 03:09:00,177 --> 03:09:01,545 TO CHANGES IN THEIR ENVIRONMENT. 3193 03:09:01,545 --> 03:09:04,849 WE WENT AHEAD AND LOOKED AT 3194 03:09:04,849 --> 03:09:06,150 MYH10 BETTER. 3195 03:09:06,150 --> 03:09:09,186 THE RATIONALE WAS IT CON 3196 03:09:09,186 --> 03:09:13,190 FUNCTION AS A COLLAGEN CHAPERONE 3197 03:09:13,190 --> 03:09:17,128 AND HAS BEEN IMPLICATED IN 3198 03:09:17,128 --> 03:09:18,929 CARDIOMYOPATHY AND VALVE DISEASE 3199 03:09:18,929 --> 03:09:21,966 SO A LOGICAL CANDIDATE TO GO 3200 03:09:21,966 --> 03:09:32,076 AFTER. 3201 03:09:36,380 --> 03:09:38,249 ON THE LEFT IS OUR FLOW CHART OF 3202 03:09:38,249 --> 03:09:39,483 WHAT WE'RE DOING. 3203 03:09:39,483 --> 03:09:42,586 BUT ON THE RIGHT IS YOU CAN SEE 3204 03:09:42,586 --> 03:09:43,988 UNDER HIGH STRESS ENVIRONMENT 3205 03:09:43,988 --> 03:09:48,225 WHICH IS HIGH 1, 2 AND 3 THE RED 3206 03:09:48,225 --> 03:09:49,326 PEAKS, THEY LOSE -- THEY CLOSE 3207 03:09:49,326 --> 03:09:51,495 THEIR CHROMATIN. 3208 03:09:51,495 --> 03:09:55,566 THE BLUE PEAKS REPRESENT THE 3209 03:09:55,566 --> 03:09:57,868 OPEN CHROMATIN AND IN THE LOWER 3210 03:09:57,868 --> 03:09:59,937 YOU CAN SEE THE PROFOUND 3211 03:09:59,937 --> 03:10:05,476 DIFFERENCE FROM THE ONE REGION. 3212 03:10:05,476 --> 03:10:10,014 THAT ONE REGION IS VERY 3213 03:10:10,014 --> 03:10:11,182 INTERESTED IN THAT BECAUSE 3214 03:10:11,182 --> 03:10:15,453 THAT'S ONE OF THE MAJOR CHANGES 3215 03:10:15,453 --> 03:10:17,822 IN THE CELLS AND WE'RE 3216 03:10:17,822 --> 03:10:20,424 INTERESTED IN WHAT IS BINDING 3217 03:10:20,424 --> 03:10:21,092 AND REGULATING TO THAT SPECIFIC 3218 03:10:21,092 --> 03:10:31,235 REGION. 3219 03:10:37,675 --> 03:10:41,479 AND WE WASN'T BACK TO PATIENT 3220 03:10:41,479 --> 03:10:45,549 BIOPSIES FROM MICHAEL BERGER'S 3221 03:10:45,549 --> 03:10:50,488 GROUP AND IN THE FIBROTIC REGION 3222 03:10:50,488 --> 03:10:55,392 NYH10 HAS A FIBROBLAST AND 3223 03:10:55,392 --> 03:10:56,427 ENDOTHELIAL MARKER AND IN 3224 03:10:56,427 --> 03:10:58,963 PATIENT BIOPSIES THERE'S 3225 03:10:58,963 --> 03:11:03,868 SIGNIFICANT ELEVATION IN NCH10 3226 03:11:03,868 --> 03:11:07,304 AND SPECIFIC FOR THE FIBROTIC 3227 03:11:07,304 --> 03:11:08,506 REGIONS AND NOT ATHLETE 3228 03:11:08,506 --> 03:11:16,247 NON-STRESSED PARTS OF THE HEART. 3229 03:11:16,247 --> 03:11:17,681 COLLECTIVELY THIS IS CONSISTENT 3230 03:11:17,681 --> 03:11:18,249 WITH IN VITRO. 3231 03:11:18,249 --> 03:11:19,984 WE'VE TAKEN BASICALLY 3232 03:11:19,984 --> 03:11:21,619 REDUCTIONIST APPROACH AND TAKING 3233 03:11:21,619 --> 03:11:23,954 CELLS IN A DISH. 3234 03:11:23,954 --> 03:11:26,857 ASKED THE QUESTION OF WHAT IS 3235 03:11:26,857 --> 03:11:27,191 BEING CHANGED. 3236 03:11:27,191 --> 03:11:30,494 BOTH AT A MOLECULAR AND GENOMIC 3237 03:11:30,494 --> 03:11:32,830 LEVEL AND THEN TAKING THAT BACK 3238 03:11:32,830 --> 03:11:36,433 TO VALIDATE IT IN THE HUMAN 3239 03:11:36,433 --> 03:11:46,610 BIOPSIES. 3240 03:11:48,312 --> 03:11:51,849 WE'RE TRYING TO UNDERSTAND WHAT 3241 03:11:51,849 --> 03:11:54,652 IT HOLDS AS INFORMATION. 3242 03:11:54,652 --> 03:11:57,888 AND WE WANT TO WORK UP STREAM TO 3243 03:11:57,888 --> 03:12:00,724 IDENTIFY WHAT IS SIMULATING THE 3244 03:12:00,724 --> 03:12:10,267 REGULATION AND CAUSING THE 3245 03:12:10,267 --> 03:12:10,534 INCREASE. 3246 03:12:10,534 --> 03:12:11,735 AND FROM VARIOUS TATE SETS AND 3247 03:12:11,735 --> 03:12:16,440 NETWORK IDENTIFICATION WE WERE 3248 03:12:16,440 --> 03:12:19,109 ABLE TO IDENTIFY THREE MAIN 3249 03:12:19,109 --> 03:12:19,844 TRANSCRIPTION FACTORS AS 3250 03:12:19,844 --> 03:12:29,320 MECHANICALLY SENSITIVE TARGETS. 3251 03:12:29,320 --> 03:12:30,321 THEY'RE RELGULATED IN THE AREAS 3252 03:12:30,321 --> 03:12:30,921 OF HIGH STRESS. 3253 03:12:30,921 --> 03:12:32,456 WHY IS THIS IMPORTANT? 3254 03:12:32,456 --> 03:12:35,226 IF YOU IDENTIFY THE SEGMENTS AND 3255 03:12:35,226 --> 03:12:39,830 FACTORS AND TRANSCRIPTION OR 3256 03:12:39,830 --> 03:12:45,369 OTHER ELEMENTS IN THE CELL AND 3257 03:12:45,369 --> 03:12:46,237 THERAPEUTIC INTERVENTION AS WELL 3258 03:12:46,237 --> 03:12:48,005 AS DEVELOPING MOLECULAR PROBES 3259 03:12:48,005 --> 03:12:48,539 THAT CAN RECOGNIZE THESE 3260 03:12:48,539 --> 03:12:51,442 TARGETS. 3261 03:12:51,442 --> 03:12:53,143 SO THAT CAN GO BACK AND ASIDE 3262 03:12:53,143 --> 03:12:54,645 FROM UNDERSTANDING THE 3263 03:12:54,645 --> 03:12:58,983 MECHANISTIC BASIS OF THE 3264 03:12:58,983 --> 03:13:01,552 PROGRESSION OF THIS DISEASE WE 3265 03:13:01,552 --> 03:13:03,854 CAN ARM PHYSICIANS WITH TOOLS TO 3266 03:13:03,854 --> 03:13:05,756 SAY YES, THE PATIENT IS 3267 03:13:05,756 --> 03:13:06,056 PROGRESSING. 3268 03:13:06,056 --> 03:13:09,860 THE FIBROTIC REGION OF THE 3269 03:13:09,860 --> 03:13:10,961 PATIENT IS PROGRESSION IN A 3270 03:13:10,961 --> 03:13:12,162 DIFFERENT WAY THAN THE VALVE AND 3271 03:13:12,162 --> 03:13:12,796 MAYBE WE NEED A DIFFERENT 3272 03:13:12,796 --> 03:13:23,040 INTERVENTION. 3273 03:13:24,642 --> 03:13:27,211 WE'VE DEMONSTRATED THE 3274 03:13:27,211 --> 03:13:29,847 FIBROBLASTS HAVE THE ABILITY TO 3275 03:13:29,847 --> 03:13:36,086 SENSE AND RESPOND TO MECHANICAL 3276 03:13:36,086 --> 03:13:38,055 CHANGES BY GLOBAL EXPRESSION RNA 3277 03:13:38,055 --> 03:13:44,695 AND CHROMATIN ACCESSIBILITY. 3278 03:13:44,695 --> 03:13:47,498 THERE ARE REGULATORS THAT DON'T 3279 03:13:47,498 --> 03:13:50,968 JUST REGULATE ONE GENE BUT MAY 3280 03:13:50,968 --> 03:13:53,270 REGULATE A HOST OF FWEENZ TO 3281 03:13:53,270 --> 03:13:56,173 AMPLIFY A FIBROTIC RESPONSE. 3282 03:13:56,173 --> 03:14:02,112 AND INTERFWRITING SINGLE CELL 3283 03:14:02,112 --> 03:14:05,049 RNA SEQ HAS BEEN REVIEWING OF A 3284 03:14:05,049 --> 03:14:08,118 NEW MECHANISM AND NOW 3285 03:14:08,118 --> 03:14:10,454 APPLICATIONS IN HUMAN AND MOUSE 3286 03:14:10,454 --> 03:14:14,325 BIOPSIES AS A VALIDATION CORE IS 3287 03:14:14,325 --> 03:14:17,394 IMPORTANT AS WELL AS IN BOB 3288 03:14:17,394 --> 03:14:18,963 LAVIGNE'S LARGE ANIMAL MODEL 3289 03:14:18,963 --> 03:14:19,530 WILL BE INCREDIBLY TELLING 3290 03:14:19,530 --> 03:14:21,865 BECAUSE IT'S A SURGICAL MODEL 3291 03:14:21,865 --> 03:14:27,071 MAYBE YOU'LL TALK ABOUT LATER 3292 03:14:27,071 --> 03:14:29,940 THAT GETS AROUND ANY GENETIC 3293 03:14:29,940 --> 03:14:31,241 QUESTION. 3294 03:14:31,241 --> 03:14:32,543 SO MAYBE IN THE END AND MAYBE 3295 03:14:32,543 --> 03:14:34,111 IT'S SO COMPLICATED IT'S GIVING 3296 03:14:34,111 --> 03:14:38,215 US A TOOL TO STUDY THE DISEASE. 3297 03:14:38,215 --> 03:14:41,385 THE SECONDARY TERTIARY 3298 03:14:41,385 --> 03:14:43,053 CONSEQUENCES OF WHATEVER 3299 03:14:43,053 --> 03:14:45,823 MUTATION YOU HAVE IS REALLY WHAT 3300 03:14:45,823 --> 03:14:56,333 NEEDS TO BE ALSO FOCUSSED ON. 3301 03:15:00,304 --> 03:15:03,941 AND NATURAL HISTORY OF DISEASE 3302 03:15:03,941 --> 03:15:14,351 NEEDS TO BE INTEGRATED. 3303 03:15:23,861 --> 03:15:34,304 AND HOW DOES THIS TRANSLATING. 3304 03:15:55,059 --> 03:15:56,126 REPLACEMENT FIBROSIS IS THE 3305 03:15:56,126 --> 03:16:01,098 POINT OF NO RETURN. 3306 03:16:01,098 --> 03:16:07,704 SO WE NEED TO LEARN MORE ABOUT 3307 03:16:07,704 --> 03:16:09,106 EPIGENETIC VARIANTS AND WHAT ARE 3308 03:16:09,106 --> 03:16:12,443 THE ROLE OF CHANNEL ON THE GENE 3309 03:16:12,443 --> 03:16:17,347 AND CARDIOMYOPATHY FWEENZ WE 3310 03:16:17,347 --> 03:16:19,316 KNOW THEY'RE PLAYERS. 3311 03:16:19,316 --> 03:16:24,822 AND YOU CAN TWO THROUGH THESE 3312 03:16:24,822 --> 03:16:35,365 THINGS AND SEE IF WE SHOULD BE 3313 03:16:44,174 --> 03:16:45,876 DOING BIOMARKERS FROM PATIENTS 3314 03:16:45,876 --> 03:16:48,145 AT DIFFERENT TIMES IN STUDIES. 3315 03:16:48,145 --> 03:16:51,815 AND CAN MOLECULAR DRIVERS OF 3316 03:16:51,815 --> 03:16:54,151 FIBROSIS BE REVERSED AND THAT 3317 03:16:54,151 --> 03:16:55,285 ATTRIBUTE TO ARRHYTHMIAS. 3318 03:16:55,285 --> 03:16:56,386 THE QUESTIONS ARE MANY. 3319 03:16:56,386 --> 03:16:58,889 I'LL LEAVE IT AT THAT. 3320 03:16:58,889 --> 03:17:04,595 THANK YOU FOR THE OPPORTUNITY TO 3321 03:17:04,595 --> 03:17:04,828 SPEAK. 3322 03:17:04,828 --> 03:17:14,638 AND BOB LAVIGNE IN PARTICULAR 3323 03:17:14,638 --> 03:17:16,707 HAS BEEN A CONTRIBUTOR TO THIS 3324 03:17:16,707 --> 03:17:18,475 AND LARGELY CONTRIBUTED TO MY 3325 03:17:18,475 --> 03:17:18,976 THINKING ON THIS MATTER. 3326 03:17:18,976 --> 03:17:27,751 THANK YOU. 3327 03:17:28,085 --> 03:17:32,623 >> PHENOMENAL. 3328 03:17:32,623 --> 03:17:34,124 ALWAYS YOU NEVER CEASE TO 3329 03:17:34,124 --> 03:17:36,426 INSPIRE OUR THINKING IN VERY 3330 03:17:36,426 --> 03:17:37,828 VERY EXCITING WAYS. 3331 03:17:37,828 --> 03:17:39,129 I THINK ONE OF THE INTERESTING 3332 03:17:39,129 --> 03:17:42,666 QUESTIONS YOU ALLUDED TO AT THE 3333 03:17:42,666 --> 03:17:44,434 END IS THERE REVERSIBILITY. 3334 03:17:44,434 --> 03:17:47,638 THAT'S ALWAYS BEEN THE QUESTION 3335 03:17:47,638 --> 03:17:51,141 IN TERMS OF PARTICULARLY DOES 3336 03:17:51,141 --> 03:17:55,279 SURGERY HELP REDUCE THE RISK OF 3337 03:17:55,279 --> 03:17:56,446 ARRHYTHMIAS AND IF THE FIBROSIS 3338 03:17:56,446 --> 03:18:00,450 IS THERE AND REPLACEMENT 3339 03:18:00,450 --> 03:18:02,119 FIBROSIS DOES IT GO AWAY? 3340 03:18:02,119 --> 03:18:03,820 I THINK ONLY THE KIND OF 3341 03:18:03,820 --> 03:18:08,091 ANALYSIS YOU'RE DOING ONLY 3342 03:18:08,091 --> 03:18:10,594 THROUGH THAT CAN WE POSSIBLY 3343 03:18:10,594 --> 03:18:12,796 CONSIDER WAYS TO REDUCE THE 3344 03:18:12,796 --> 03:18:13,297 FIBROSIS. 3345 03:18:13,297 --> 03:18:17,401 I WAS A SYMPOSIUM FOR TWO DAYS 3346 03:18:17,401 --> 03:18:20,971 IN BOSTON CALLED THE 3347 03:18:20,971 --> 03:18:22,673 ANTI-FIBROTIC DRUG THERAPY 3348 03:18:22,673 --> 03:18:24,441 DEVELOPMENT AND PEOPLE FROM 3349 03:18:24,441 --> 03:18:26,510 ACADEMIA AND INDUSTRY AND IT'S 3350 03:18:26,510 --> 03:18:27,211 INTERESTING INDUSTRY IS 3351 03:18:27,211 --> 03:18:32,449 INTERESTED IN LOOKING AT THE 3352 03:18:32,449 --> 03:18:34,151 SAME SINGLE CELL SEQUENCING TATE 3353 03:18:34,151 --> 03:18:39,856 AND TRYING TO FIND AND THEY ARE 3354 03:18:39,856 --> 03:18:43,560 DON'T HAVE A GOOD MODEL YET FOR 3355 03:18:43,560 --> 03:18:45,329 FIBROSIS BUT ACHIEVING THE 3356 03:18:45,329 --> 03:18:47,531 REVERSAL OF FIBROSIS WOULD BE AN 3357 03:18:47,531 --> 03:18:48,031 AMAZING COUP. 3358 03:18:48,031 --> 03:18:58,542 THANK YOU FOR THE INSPIRATION. 3359 03:19:51,361 --> 03:19:54,264 >> I'M EXCITED TO WORK WORTH YOU 3360 03:19:54,264 --> 03:19:55,632 ON THE BASIC -- THE SAME 3361 03:19:55,632 --> 03:20:01,672 QUESTIONS IN A MODEL WHERE YOU 3362 03:20:01,672 --> 03:20:11,948 CAN DISSECT -- 3363 03:20:27,764 --> 03:20:31,101 >> WE HAVE BEEN WORKING ON 3364 03:20:31,101 --> 03:20:34,271 BUILDING THE GENOME. 3365 03:20:34,271 --> 03:20:36,707 >> AND IN GOATS IT'S 3366 03:20:36,707 --> 03:20:37,007 CHALLENGING. 3367 03:20:37,007 --> 03:20:40,811 WE HAVE GAPS SO I DON'T KNOW 3368 03:20:40,811 --> 03:20:41,912 ABOUT SHEEP. 3369 03:20:41,912 --> 03:20:44,448 >> SHEEP ARE WORSE. 3370 03:20:44,448 --> 03:20:52,689 >> OKAY. 3371 03:20:52,689 --> 03:20:54,691 >> IS THE LIST OF IDENTIFIED 3372 03:20:54,691 --> 03:20:57,561 GENES PUBLICALLY AVAILABLE IN 3373 03:20:57,561 --> 03:20:58,995 ADDITION TO GENETIC VARIATION IS 3374 03:20:58,995 --> 03:21:00,464 THERE ANY INFORMATION AVAILABLE 3375 03:21:00,464 --> 03:21:03,867 REGARDING TRANSCRIPTOMIC AND 3376 03:21:03,867 --> 03:21:05,035 PROTEOMIC CHANGES. 3377 03:21:05,035 --> 03:21:07,637 >> SO WE DON'T HAVE PROTEOMIC 3378 03:21:07,637 --> 03:21:08,205 DATA AVAILABLE. 3379 03:21:08,205 --> 03:21:11,742 IT'S AGAIN THE SAME CHALLENGES 3380 03:21:11,742 --> 03:21:15,612 WHEN YOU ARE DEALING WITH THE 3381 03:21:15,612 --> 03:21:16,179 MITRAL VALVE TISSUE. 3382 03:21:16,179 --> 03:21:19,182 ANYBODY WHO WORKED WITH THAT 3383 03:21:19,182 --> 03:21:20,917 IT'S DIFFICULT TO HANDLE. 3384 03:21:20,917 --> 03:21:24,521 WE WERE HAPPY TO GET THE ATAC 3385 03:21:24,521 --> 03:21:26,156 MAP ONE DAY AND MOTIVATED TO DO 3386 03:21:26,156 --> 03:21:27,724 IT AGAIN. 3387 03:21:27,724 --> 03:21:33,430 IT WAS A NIGHTMARE TO GET IT OUT 3388 03:21:33,430 --> 03:21:34,064 OF THE TISSUE. 3389 03:21:34,064 --> 03:21:44,408 THE WEEKS OR MONTHS TO GET THIS 3390 03:21:44,408 --> 03:21:46,209 IN THE PREPRINT AND MAYBE 3391 03:21:46,209 --> 03:21:48,345 AVAILABLE AND PEOPLE CAN LOOK IN 3392 03:21:48,345 --> 03:21:50,347 DETAIL INTO THOSE MECHANISMS. 3393 03:21:50,347 --> 03:21:50,547 YEAH. 3394 03:21:50,547 --> 03:21:55,986 >> THANK YOU. 3395 03:21:55,986 --> 03:21:56,953 >> ANY OTHER QUESTIONS OR 3396 03:21:56,953 --> 03:22:07,130 COMMENTS? 3397 03:22:09,566 --> 03:22:14,504 >> I HAVE A QUESTION FOR CHIP IN 3398 03:22:14,504 --> 03:22:17,941 TERMS OF REVERSAL. 3399 03:22:17,941 --> 03:22:21,411 I ASSUME IT'S DIFFERENT THAN 3400 03:22:21,411 --> 03:22:22,479 FIBROSIS AND IS THERE A WAY YOU 3401 03:22:22,479 --> 03:22:24,448 CAN STUDY THIS AT THE ANIMAL 3402 03:22:24,448 --> 03:22:25,515 MODEL LEVEL? 3403 03:22:25,515 --> 03:22:31,555 >> YEAH, SO THE MOUSE DOESN'T -- 3404 03:22:31,555 --> 03:22:35,425 ONLY IN RARE SITUATIONS DOES THE 3405 03:22:35,425 --> 03:22:40,197 MVP MOUSE MODEL DEVELOP TRUE 3406 03:22:40,197 --> 03:22:43,633 REPLACEMENT FIBROSIS OR VERY 3407 03:22:43,633 --> 03:22:44,401 SPECIFIC REGIONS. 3408 03:22:44,401 --> 03:22:49,639 MOST IS INTERSTITIAL FIBROSIS. 3409 03:22:49,639 --> 03:22:51,842 SO THAT WOULD BE A GOOD MODEL TO 3410 03:22:51,842 --> 03:22:55,512 SEE IF WE COULD REVERSE THE 3411 03:22:55,512 --> 03:22:56,947 INTERSTITIAL FIBROSIS. 3412 03:22:56,947 --> 03:22:59,716 REPLACEMENT OF FIBROSIS IS 3413 03:22:59,716 --> 03:23:00,617 PRETTY MUCH DONE. 3414 03:23:00,617 --> 03:23:04,187 IT'S HARD TO IMAGINE HOW YOU CAN 3415 03:23:04,187 --> 03:23:13,063 BLAST THROUGH THE CONCRETE 3416 03:23:13,063 --> 03:23:14,764 THERE'S OTHER MODEL SYSTEMS YOU 3417 03:23:14,764 --> 03:23:18,068 CAN USE TO ASK THAT QUESTION. 3418 03:23:18,068 --> 03:23:21,505 ORGANOIDS AND 3-D CULTURE 3419 03:23:21,505 --> 03:23:22,239 SYSTEMS. 3420 03:23:22,239 --> 03:23:26,343 BUT AS FAR AS THE MOUSE GOES, 3421 03:23:26,343 --> 03:23:28,078 MOST OF THE FIBROSIS IS MORE 3422 03:23:28,078 --> 03:23:36,553 INTERSTITIAL. 3423 03:23:36,553 --> 03:23:39,523 >> AND REDUCE PROGRESSION FOR 3424 03:23:39,523 --> 03:23:40,490 THE SIZE. 3425 03:23:40,490 --> 03:23:43,426 >> WE SEE A CLEAR INCREASE IN 3426 03:23:43,426 --> 03:23:46,663 THE AMOUNT OF COLLAGEN 3427 03:23:46,663 --> 03:23:50,300 DEPOSITION AND SO WE'RE JUST NOT 3428 03:23:50,300 --> 03:24:00,810 KILLING MYOCYTES HUMANS HAVE. 3429 03:24:03,680 --> 03:24:06,516 OUR TIME PERIOD IS SIX MONTHS 3430 03:24:06,516 --> 03:24:07,217 VERSUS 60 YEARS. 3431 03:24:07,217 --> 03:24:12,322 IT'S A LITTLE BIT HARD TO 3432 03:24:12,322 --> 03:24:14,457 COMPARE THOSE. 3433 03:24:14,457 --> 03:24:17,928 IF WE CAN FIND A WAY TO SUPPRESS 3434 03:24:17,928 --> 03:24:20,130 OR RESTRICT THE FIBROTIC 3435 03:24:20,130 --> 03:24:21,331 PROCESS, THEN I THINK THAT'S 3436 03:24:21,331 --> 03:24:22,999 GOING TO BE GOOD. 3437 03:24:22,999 --> 03:24:27,604 AND CERTAINLY GOING THROUGH 3438 03:24:27,604 --> 03:24:30,674 HIGHER ORDER MALES, BOB'S MODEL 3439 03:24:30,674 --> 03:24:36,279 OF THE SHEEP HAS PROFOUND 3440 03:24:36,279 --> 03:24:36,947 REPLACEMENTS FIBROSIS. 3441 03:24:36,947 --> 03:24:39,516 YOU'D GO UP THE CHAIN TO SEE IF 3442 03:24:39,516 --> 03:24:41,785 THE MECHANISM YOU'VE IDENTIFIED 3443 03:24:41,785 --> 03:24:44,220 IN THE LOWER MANTLE IS WORKING 3444 03:24:44,220 --> 03:24:48,892 IN A LARGER ANIMAL. 3445 03:24:48,892 --> 03:24:54,497 >> YOU CAN ALSO SORT OUT THE 3446 03:24:54,497 --> 03:25:02,772 INFLUENCE OF REGURGITATION THE 3447 03:25:02,772 --> 03:25:04,207 MOUSE BECAUSE IT'S HARD TO 3448 03:25:04,207 --> 03:25:06,309 IMAGINE THE NATURAL 3449 03:25:06,309 --> 03:25:06,643 REGURGITATION. 3450 03:25:06,643 --> 03:25:08,812 >> AND IT'S HARD TO HAVE A MODEL 3451 03:25:08,812 --> 03:25:15,919 WHERE YOU JUST HAVE MR ONLY SO 3452 03:25:15,919 --> 03:25:19,522 IT'S VERY DIFFICULT IN THE 3453 03:25:19,522 --> 03:25:29,633 MOU 3454 03:25:32,502 --> 03:25:32,902 MOUSE. 3455 03:25:32,902 --> 03:25:43,246 IT'S A FAST RHYTHM. 3456 03:25:59,696 --> 03:26:00,697 UTILITIES CAN BE SIGNIFICANT AS 3457 03:26:00,697 --> 03:26:09,773 FAR AS THE SURGICAL APPROACH. 3458 03:26:09,773 --> 03:26:10,373 >> GREAT TALKS. 3459 03:26:10,373 --> 03:26:12,742 I WANTED TO GO BACK TO THE 3460 03:26:12,742 --> 03:26:15,912 CLINICAL WORLD FOR A SECOND AND 3461 03:26:15,912 --> 03:26:19,482 MAYBE YOU COULD THIS AND JUST 3462 03:26:19,482 --> 03:26:21,584 CURIOUS IN PATIENTS GETTING 3463 03:26:21,584 --> 03:26:25,989 CLINICAL TARGETED EXOME, WHICH 3464 03:26:25,989 --> 03:26:28,425 ARE TESTED IN FRANCE FOR EXAMPLE 3465 03:26:28,425 --> 03:26:30,493 AND CURIOUS ABOUT THE DIFFERENCE 3466 03:26:30,493 --> 03:26:32,429 IN TESTING BETWEEN HERE AND 3467 03:26:32,429 --> 03:26:36,199 FRANCE. 3468 03:26:36,199 --> 03:26:38,735 >> IN THE CLINICAL PRACTICE? 3469 03:26:38,735 --> 03:26:39,335 >> YES. 3470 03:26:39,335 --> 03:26:43,173 >> IN CLINICAL PRACTICE WE DON'T 3471 03:26:43,173 --> 03:26:45,508 HAVE THE GENETICS OF THE 3472 03:26:45,508 --> 03:26:47,911 PROLAPSE BECAUSE THERE ARE A FEW 3473 03:26:47,911 --> 03:26:53,349 MEMBERS OF GENES IDENTIFIED SO 3474 03:26:53,349 --> 03:27:03,793 FAR AND HAVE THE GENETICS 3475 03:27:08,932 --> 03:27:10,867 OUTSIDE THE RESEARCH BUT WE 3476 03:27:10,867 --> 03:27:13,503 DIDN'T FIND MANY WITH PATHOGENIC 3477 03:27:13,503 --> 03:27:17,540 MUTATION IN OUR SEGMENTS AROUND 3478 03:27:17,540 --> 03:27:23,012 300 PATIENTS WITH FULL GENOME 3479 03:27:23,012 --> 03:27:27,317 AND WE DIDN'T FIND A NEW FAMILY 3480 03:27:27,317 --> 03:27:37,794 OR WITH A SPECIFIC MUTATION 3481 03:27:39,162 --> 03:27:42,465 INVOLVING THE PROLAPSE AND A 3482 03:27:42,465 --> 03:27:43,700 DIFFERENT STATE THAN OTHER 3483 03:27:43,700 --> 03:27:44,033 CASES. 3484 03:27:44,033 --> 03:27:46,569 >> MAYBE YOU CAN CONFIRM MAYBE 3485 03:27:46,569 --> 03:27:50,874 THE CONTEXT OF SYNDROMES OR 3486 03:27:50,874 --> 03:27:53,009 ARRHYTHMIA IS RECOMMENDED IF WE 3487 03:27:53,009 --> 03:27:59,048 HAVE AN AARRHYTHMIC GENE AND 3488 03:27:59,048 --> 03:28:00,950 THERE'S GENETIC TESTING. 3489 03:28:00,950 --> 03:28:06,556 FOR EXAMPLE WE HAVE CENTERS 3490 03:28:06,556 --> 03:28:12,228 WHERE THE PATIENTS ARE BUT IT'S 3491 03:28:12,228 --> 03:28:18,835 IN THE PRESENTATION AND OFTEN 3492 03:28:18,835 --> 03:28:19,402 DISCOVERED LATER. 3493 03:28:19,402 --> 03:28:25,008 >> IT COULD BE THE FIRST STEP IN 3494 03:28:25,008 --> 03:28:27,443 MITRAL VALVE PROLAPSE AND 3495 03:28:27,443 --> 03:28:28,444 DIALYSIS AND WE HAVE FAMILIES 3496 03:28:28,444 --> 03:28:32,415 WITH THE SYNDROME. 3497 03:28:32,415 --> 03:28:42,959 WHEN I WE HAVE PROLAPSE AND THE 3498 03:28:43,426 --> 03:28:44,561 SYNDROME AFTER EXAMINATION 3499 03:28:44,561 --> 03:28:46,496 SOMETIMES I SEND THE PATIENT FOR 3500 03:28:46,496 --> 03:28:56,439 GENETIC TESTING OF THE SIN -- 3501 03:28:56,439 --> 03:29:03,947 SYNDROME AND WITH PATIENTS WITH 3502 03:29:03,947 --> 03:29:12,455 SUDDEN DEATH WE PERFORM TESTS 3503 03:29:12,455 --> 03:29:22,932 AND IT'S A FAMILY WITH THE 3504 03:29:29,138 --> 03:29:32,342 MOTHER AND DAUGHTER WITH THE 3505 03:29:32,342 --> 03:29:40,884 SAME PHENOTYPES IN THE GENE 3506 03:29:40,884 --> 03:29:42,151 SEQUENCING AND THERE WERE NO 3507 03:29:42,151 --> 03:29:52,495 KNOCK FOR THE MODEL. 3508 03:29:54,197 --> 03:29:56,132 >> WE HAVE A QUESTION FROM CHIP 3509 03:29:56,132 --> 03:29:57,567 FROM THE VIDEOCAST. 3510 03:29:57,567 --> 03:29:59,135 WHAT KIND OF STRESS ARE THE 3511 03:29:59,135 --> 03:30:00,203 FIBROBLASTS EXPERIENCING AND 3512 03:30:00,203 --> 03:30:06,209 WHAT ARE THE SENSORS? 3513 03:30:06,209 --> 03:30:08,411 >> WE DON'T KNOW WHAT THE SENSES 3514 03:30:08,411 --> 03:30:10,947 ARE ON THE CELLS. 3515 03:30:10,947 --> 03:30:13,683 WE THINK -- SENSORS ARE ON THE 3516 03:30:13,683 --> 03:30:14,217 CELLS. 3517 03:30:14,217 --> 03:30:16,352 WE THINK THEY'RE MEMBRANE BOUND. 3518 03:30:16,352 --> 03:30:21,925 WE THOUGHT FOR A WHILE THEY MAY 3519 03:30:21,925 --> 03:30:30,033 BE CONNEX OMS BUT DIFFERENT 3520 03:30:30,033 --> 03:30:37,006 RESPONSES ON FIBE REBLASTS. 3521 03:30:37,006 --> 03:30:38,675 -- FIBROBLASTS. 3522 03:30:38,675 --> 03:30:41,411 WE HAVE STRETCHED THE CELLS AT 3523 03:30:41,411 --> 03:30:48,418 DIFFERENT AMPLITUDES AND UNDER 3524 03:30:48,418 --> 03:30:53,222 PATH LOGIC STRAIN VERSUS LOW 3525 03:30:53,222 --> 03:30:54,390 STRESS. 3526 03:30:54,390 --> 03:30:57,527 AND A SECOND APPROACH WAS--THAT 3527 03:30:57,527 --> 03:31:04,500 WOULD MODEL THE EARLY STAGES OF 3528 03:31:04,500 --> 03:31:07,036 PROLAPSING VALVE OR PRODOMAL 3529 03:31:07,036 --> 03:31:10,673 FORM AND ALSO DID STUDIES WHERE 3530 03:31:10,673 --> 03:31:13,409 WE PUT IT THE FIBROBLAST VERSUS 3531 03:31:13,409 --> 03:31:18,214 STIFF VERSUS VERY SOFT. 3532 03:31:18,214 --> 03:31:21,551 AND SUBSTRATES AND DID THE SAME 3533 03:31:21,551 --> 03:31:23,519 STUDIES TO ASK THE QUESTION OF 3534 03:31:23,519 --> 03:31:28,224 WHETHER OR NOT THE SUBSTRATES 3535 03:31:28,224 --> 03:31:31,394 ARE SUFFICIENT AND NECESSARY FOR 3536 03:31:31,394 --> 03:31:33,963 AMPLIFYING A RESPONSE OF THE 3537 03:31:33,963 --> 03:31:36,966 FIBROBLASTS OR THE FIBROBLAST 3538 03:31:36,966 --> 03:31:38,935 JUST SHUT OFF. 3539 03:31:38,935 --> 03:31:45,975 IS A CONTINUAL PROCESS AND 3540 03:31:45,975 --> 03:31:48,444 AMPLIFIES THE COLLAGEN AND 3541 03:31:48,444 --> 03:31:55,985 FIBROTIC RESPONSE IN THE CELLS. 3542 03:31:55,985 --> 03:31:57,587 >> THANK YOU. 3543 03:31:57,587 --> 03:31:59,522 WE'RE GOING TO TAKE ANOTHER 3544 03:31:59,522 --> 03:32:00,556 BRIEF BREAK AND RETURN 10 3545 03:32:00,556 --> 03:32:01,991 MINUTES AFTER THE HOUR AND 3546 03:32:01,991 --> 03:32:02,625 RETURN FOR THE FINAL SESSION OF 3547 03:32:02,625 --> 03:32:06,841 THE DAY. 3548 03:32:06,841 --> 03:32:11,879 THE FIRST PRESENTATION OF THIS 3549 03:32:11,879 --> 03:32:21,522 SESSION WILL BE FROM THIERRY LE 3550 03:32:21,522 --> 03:32:21,956 TURNEAU. 3551 03:32:21,956 --> 03:32:23,724 >> THANK YOU FOR LETTING ME 3552 03:32:23,724 --> 03:32:29,030 DISCUSS THE INTERVENTION AND 3553 03:32:29,030 --> 03:32:29,297 RESEARCH. 3554 03:32:29,297 --> 03:32:33,334 WE MAY NEED TO HAVE THE MEETINGS 3555 03:32:33,334 --> 03:32:37,371 DURING THE NET WORK SO IT'S 3556 03:32:37,371 --> 03:32:37,972 FRIENDLY MEETING TODAY AND I 3557 03:32:37,972 --> 03:32:47,782 APPRECIATE THAT. 3558 03:32:47,782 --> 03:32:49,917 I DON'T HAVE DISCLOSURE 3559 03:32:49,917 --> 03:32:56,724 REGARDING THE PRESENTATION. 3560 03:32:56,724 --> 03:33:03,264 SO AS YOU PROBABLY NOW THE FIRST 3561 03:33:03,264 --> 03:33:08,336 STEPS WERE ELABORATED DURING THE 3562 03:33:08,336 --> 03:33:09,737 SECOND WORLD WAR. 3563 03:33:09,737 --> 03:33:14,442 AND THE MACHINE WAS ABLE TO 3564 03:33:14,442 --> 03:33:21,582 DECODE AND PROVIDE THE ADVANTAGE 3565 03:33:21,582 --> 03:33:24,685 DURING THE SECOND WORLD WAR. 3566 03:33:24,685 --> 03:33:26,487 SO THE DEFINITION OF ARTIFICIAL 3567 03:33:26,487 --> 03:33:29,023 INTELLIGENCE IS THE ABILITY OF 3568 03:33:29,023 --> 03:33:34,128 MACHINES, COMPUTERS TO PERFORM 3569 03:33:34,128 --> 03:33:39,934 TASK THAT REQUIRE HUMAN 3570 03:33:39,934 --> 03:33:40,468 INTELLIGENCE AND MACHINE 3571 03:33:40,468 --> 03:33:43,070 LEARNING IS WHERE COMPUTERS ARE 3572 03:33:43,070 --> 03:33:50,878 ABLE TO IMPROVE AND LEARN 3573 03:33:50,878 --> 03:33:51,212 AUTOMATICALLY. 3574 03:33:51,212 --> 03:33:52,580 MACHINE LEARNING ALGORITHM USES 3575 03:33:52,580 --> 03:33:54,982 DATA TO BUILD MODELS AND MAKE 3576 03:33:54,982 --> 03:33:55,883 PREDICTIONS OR DECISION AND DEEP 3577 03:33:55,883 --> 03:33:59,286 LEARNING IS RAY NEW SUB-CATEGORY 3578 03:33:59,286 --> 03:34:03,557 BASED ON MULTI-LAYERED 3579 03:34:03,557 --> 03:34:05,059 ARTIFICIAL NEURAL NETWORKS WHICH 3580 03:34:05,059 --> 03:34:08,362 IS DESIGN TO MIMIC THE AND 3581 03:34:08,362 --> 03:34:09,797 FUNCTION OF THE HUMAN BRAIN IN 3582 03:34:09,797 --> 03:34:10,731 THE COMPUTER. 3583 03:34:10,731 --> 03:34:13,234 IT'S AN IMPROVEMENT COMPARED TO 3584 03:34:13,234 --> 03:34:18,105 BASIC MACHINE LEARNING. 3585 03:34:18,105 --> 03:34:24,311 FINALLY, TOPOLOGICAL OR 3586 03:34:24,311 --> 03:34:25,513 GEOMETRIC DATA ANALYSIS CAN 3587 03:34:25,513 --> 03:34:30,184 PROVIDE A SHAPE AND APPLIED TO 3588 03:34:30,184 --> 03:34:33,754 MACHINE LEARNING AND MACHINE 3589 03:34:33,754 --> 03:34:44,064 LEARNING METHODS. 3590 03:34:46,233 --> 03:34:47,501 ARTIFICIAL INTELLIGENCE IS 3591 03:34:47,501 --> 03:34:50,571 EVERYWHERE IN OUR LIFE AND CAR 3592 03:34:50,571 --> 03:34:55,709 AND HOUSE AND COMPUTER FOR SURE. 3593 03:34:55,709 --> 03:35:06,253 THE APPLICATION ARE MULTIPLE BUT 3594 03:35:10,825 --> 03:35:17,097 CANNOT REPLACE HUMAN KNOWLEDGE 3595 03:35:17,097 --> 03:35:21,502 AND HERE YOU HAVE A LIST OF 3596 03:35:21,502 --> 03:35:24,839 POTENTIAL APPLICATIONS 3597 03:35:24,839 --> 03:35:26,907 STANDARDIZATION OF IMAGE 3598 03:35:26,907 --> 03:35:29,043 ACQUISITION AND AUTOMATIC 3599 03:35:29,043 --> 03:35:33,981 MEASUREMENTS AND SIMPLE OR MORE 3600 03:35:33,981 --> 03:35:38,819 COMPLEX AND CAN HELP DIAGNOSIS 3601 03:35:38,819 --> 03:35:43,924 AORTIC STENOSIS AND HELP PERFORM 3602 03:35:43,924 --> 03:35:45,626 CLUSTERING OF PATIENTS REGARDING 3603 03:35:45,626 --> 03:35:48,162 TO PHENOTYPE AND CAN DEVELOP 3604 03:35:48,162 --> 03:35:49,497 ALGORITHM WITH MACHINE LEARNING 3605 03:35:49,497 --> 03:35:50,965 FOR THE RISK ASSESSMENT OR 3606 03:35:50,965 --> 03:35:53,100 CLINICAL DECISION MAKING 3607 03:35:53,100 --> 03:36:01,709 PROCESS. 3608 03:36:01,709 --> 03:36:03,344 HERE YOU HAVE DIFFERENT STEPS 3609 03:36:03,344 --> 03:36:04,745 AND PROVIDE DATA OR VALUES TO 3610 03:36:04,745 --> 03:36:09,650 THE COMPUTERS. 3611 03:36:09,650 --> 03:36:15,756 YOU CAN PROVIDE THIS DATA IN 3612 03:36:15,756 --> 03:36:17,091 SUPERVISED APPROACH. 3613 03:36:17,091 --> 03:36:18,359 YOU CHOOSE THE DATA YOU'RE 3614 03:36:18,359 --> 03:36:25,499 PROVIDING FOR THE COMPUTER. 3615 03:36:25,499 --> 03:36:32,940 AND ASK THE COMPUTER TO MAKE A 3616 03:36:32,940 --> 03:36:34,475 DIAGNOSIS YOU WILL VALIDATE 3617 03:36:34,475 --> 03:36:35,809 AFTER THE WORK OF THE MACHINE. 3618 03:36:35,809 --> 03:36:41,081 SO YOU HAVE TO CHECK THE MODEL 3619 03:36:41,081 --> 03:36:42,783 AND HAVE TO ADVOCATE THE MODEL 3620 03:36:42,783 --> 03:36:46,387 IN THE COHORT OF PATIENTS FOR 3621 03:36:46,387 --> 03:36:46,620 EXAMPLE. 3622 03:36:46,620 --> 03:36:49,123 IT'S NOT THE END OF THE MODEL. 3623 03:36:49,123 --> 03:36:51,659 BECAUSE WE CHANGE OVER TIME AND 3624 03:36:51,659 --> 03:36:57,331 YOU HAVE TO RETRAIN THE MODEL 3625 03:36:57,331 --> 03:37:01,635 AND YOU WILL HAVE CHANGE IN THE 3626 03:37:01,635 --> 03:37:03,037 KNOWLEDGE AND TECHNOLOGICAL 3627 03:37:03,037 --> 03:37:03,637 CHANGES. 3628 03:37:03,637 --> 03:37:04,672 YOU CAN CHANGE YOUR POPULATION, 3629 03:37:04,672 --> 03:37:14,848 ETCETERA. 3630 03:37:15,549 --> 03:37:20,521 HERE YOU HAVE THE STENOSIS WHICH 3631 03:37:20,521 --> 03:37:23,657 IS INTERESTING AND USED THE LONG 3632 03:37:23,657 --> 03:37:25,526 AXIS VIEW. 3633 03:37:25,526 --> 03:37:29,863 ONLY ONE VIEW TO DIAGNOSIS THE 3634 03:37:29,863 --> 03:37:34,668 AORTIC STENOSIS AND TRAIN THE 3635 03:37:34,668 --> 03:37:38,739 MODEL AND SIMILAR TO REPLICATE 3636 03:37:38,739 --> 03:37:41,241 THE MODEL AND EXTERNAL COHORT 3637 03:37:41,241 --> 03:37:43,677 WHICH IS VERY GOOD BECAUSE 3638 03:37:43,677 --> 03:37:46,080 THEY'RE ABLE TO OBTAIN ALL THE 3639 03:37:46,080 --> 03:37:52,686 DATA FROM IMAGES TO CONFIRM THE 3640 03:37:52,686 --> 03:37:56,690 VALIDITY OF THE MODEL AND IT'S 3641 03:37:56,690 --> 03:37:57,691 VERY GOOD WHICH MEANS THE MODEL 3642 03:37:57,691 --> 03:38:03,364 WORKS VERY WELL. 3643 03:38:03,364 --> 03:38:09,303 SO A MACHINE LEARNING MODEL 3644 03:38:09,303 --> 03:38:19,847 BASED ON YOU CAN DIAGNOSIS THE 3645 03:38:23,183 --> 03:38:23,651 STENO 3646 03:38:23,651 --> 03:38:23,917 STENOSIS. 3647 03:38:23,917 --> 03:38:28,322 THERE ARE SEVERAL CAN RECENT 3648 03:38:28,322 --> 03:38:31,258 PUBLICATION AND USED MACHINE 3649 03:38:31,258 --> 03:38:34,561 LEARNING TO DIAGNOSE MODERATE 3650 03:38:34,561 --> 03:38:37,364 BASED ON THE REVIEW AND YOU CAN 3651 03:38:37,364 --> 03:38:40,634 SEE THE MODEL PERFORMED VERY 3652 03:38:40,634 --> 03:38:46,473 GOOD, VERY WELL WITH DIAGNOSIS 3653 03:38:46,473 --> 03:38:54,615 OF AT LEAST THIS MODIFICATION. 3654 03:38:54,615 --> 03:39:00,320 I DON'T KNOW WHAT IS EXACTLY THE 3655 03:39:00,320 --> 03:39:03,957 MODEL IN THE TWO INSTITUTION. 3656 03:39:03,957 --> 03:39:06,894 HERE YOU CAN SEE THE AREA IS 3657 03:39:06,894 --> 03:39:10,898 VERY GOOD WITH VALUE OF 0.9. 3658 03:39:10,898 --> 03:39:16,370 AND IN ADDITION, THE SECOND 3659 03:39:16,370 --> 03:39:20,407 STUDY THEY THE MODEL WAS ABLE TO 3660 03:39:20,407 --> 03:39:24,778 TRACK THE CHANGE OF THE TIME 3661 03:39:24,778 --> 03:39:27,514 BECAUSE SOME PATIENTS AND 3662 03:39:27,514 --> 03:39:31,418 SEVERAL ECHOCARDIOGRAPHY AND 3663 03:39:31,418 --> 03:39:34,388 SIMILAR TO THE CHANGES 3664 03:39:34,388 --> 03:39:35,222 DIAGNOSED. 3665 03:39:35,222 --> 03:39:41,095 SO IT MEANS THE MODEL WORKS VERY 3666 03:39:41,095 --> 03:39:41,428 WE 3667 03:39:41,428 --> 03:39:51,538 WELL. 3668 03:39:54,675 --> 03:39:58,212 AND WE HAVE NINE PARAMETERS AN 3669 03:39:58,212 --> 03:39:58,412 VIEWS. 3670 03:39:58,412 --> 03:40:05,519 SO IT'S A BIT MORE COMPLEX BUT 3671 03:40:05,519 --> 03:40:09,223 NEVERTHELESS IT'S FEASIBLE AND 3672 03:40:09,223 --> 03:40:10,758 FAST AND ACCURATE AND CAN MODEL 3673 03:40:10,758 --> 03:40:16,163 IN PATIENTS WITH SEVERE CASES 3674 03:40:16,163 --> 03:40:20,934 EXPECTED. 3675 03:40:20,934 --> 03:40:24,371 OUR FRENCH AND CANADIAN 3676 03:40:24,371 --> 03:40:29,510 PUBLICATION WAS PERFORMED 3677 03:40:29,510 --> 03:40:33,213 RECENTLY AND THE METHODOLOGY IS 3678 03:40:33,213 --> 03:40:37,518 A BIT MORE COMPLEX USING CARDIO 3679 03:40:37,518 --> 03:40:40,087 GRAPHY AND PARAMETERS AND PUT 3680 03:40:40,087 --> 03:40:42,823 EVERYTHING IN THE MODEL. 3681 03:40:42,823 --> 03:40:45,559 AND TRIED TO STRATIFY PATIENTS 3682 03:40:45,559 --> 03:40:51,865 IN LOW RISK AND PATIENTS WITH 3683 03:40:51,865 --> 03:40:58,372 HIGH RISK AND THEY REPLICATED 3684 03:40:58,372 --> 03:41:00,340 THE MODEL AND FOUND GOOD MODEL 3685 03:41:00,340 --> 03:41:10,717 BUT YOU KNOW IT'S MORE COMPLEX. 3686 03:41:10,717 --> 03:41:14,888 AND IT'S LESS WELL DONE WHEN YOU 3687 03:41:14,888 --> 03:41:17,124 TRY TO DIAGNOSIS BASED ONLY ON 3688 03:41:17,124 --> 03:41:18,458 THE IMAGING. 3689 03:41:18,458 --> 03:41:25,833 HERE YOU USE THE PARAMETERS BY 3690 03:41:25,833 --> 03:41:29,136 ECHOCARDIOGRAPH AND WHAT IS 3691 03:41:29,136 --> 03:41:35,776 INTERESTING IN THE MODEL IS THE 3692 03:41:35,776 --> 03:41:38,212 DIASTOLIC FUNCTION IS IMPORTANT 3693 03:41:38,212 --> 03:41:40,981 FOR THE STRATIFICATION OF THE 3694 03:41:40,981 --> 03:41:42,416 PATIENTS IN THE MODEL. 3695 03:41:42,416 --> 03:41:43,517 THE MACHINE LEARNING CAN DICTATE 3696 03:41:43,517 --> 03:41:51,692 SOME PARAMETERS OR ASPECTS OF 3697 03:41:51,692 --> 03:41:57,297 PHYSIO PATHOLOGY WE DON'T USE 3698 03:41:57,297 --> 03:41:57,598 R 3699 03:41:57,598 --> 03:42:00,000 REGULARLY TO STRATIFY PATIENTS. 3700 03:42:00,000 --> 03:42:04,671 PATIENTS WITH HIGH RISK OR 3701 03:42:04,671 --> 03:42:06,940 SEVERE ARE OFTEN REFERRED TO 3702 03:42:06,940 --> 03:42:09,142 SURGERY AND ABOUT WHAT IS 3703 03:42:09,142 --> 03:42:10,611 INTERESTING IS ONLY PATIENTS 3704 03:42:10,611 --> 03:42:13,447 WITH HIGH RISK BENEFITTED AND 3705 03:42:13,447 --> 03:42:14,982 THOSE WITH LOW RISK DIDN'T 3706 03:42:14,982 --> 03:42:25,425 BENEFIT BUT IT'S EXPECTED. 3707 03:42:31,832 --> 03:42:34,835 HERE YOU HAVE THE DATA 3708 03:42:34,835 --> 03:42:40,040 REPRESENTATION AND YOU CAN SEE 3709 03:42:40,040 --> 03:42:49,516 THE THREE GROUPS AND A GROUP B 3710 03:42:49,516 --> 03:42:52,686 WITH A PATIENT WITH DYSFUNCTION 3711 03:42:52,686 --> 03:42:59,826 AND GROUP C WITH DIASTOLIC AND 3712 03:42:59,826 --> 03:43:03,263 SYSTOLIC VENTRICULAR DYSFUNCTION 3713 03:43:03,263 --> 03:43:08,769 AND PATIENTS WITH BOTH 3714 03:43:08,769 --> 03:43:10,470 DYSFUNCTIONS COMPARED TO OTHER 3715 03:43:10,470 --> 03:43:14,942 GROUPS OF PATIENTS. 3716 03:43:14,942 --> 03:43:16,910 THE DIASTOLIC FUNCTION IS 3717 03:43:16,910 --> 03:43:18,645 IMPORTANT TO CLASSIFICATION. 3718 03:43:18,645 --> 03:43:20,547 MAYBE THANKS TO THE MACHINE 3719 03:43:20,547 --> 03:43:21,848 LEARNING MODEL WE'LL CONSIDER IN 3720 03:43:21,848 --> 03:43:25,786 A DIFFERENT WAY DIASTOLIC 3721 03:43:25,786 --> 03:43:33,527 FUNCTION FOR OUR PATIENTS WITH 3722 03:43:33,527 --> 03:43:38,131 THIS. 3723 03:43:38,131 --> 03:43:41,134 I WON'T TWO THROUGH THE SLIDE 3724 03:43:41,134 --> 03:43:43,303 BUT I WANT TO STRESS MYOCARDIAL 3725 03:43:43,303 --> 03:43:49,509 FIBERS IS A MARKER OF ADVANCED 3726 03:43:49,509 --> 03:43:59,786 ING IS A MARKER OF 3727 03:43:59,786 --> 03:44:02,222 MALDEPARTMENTIVE MODELS AND WE 3728 03:44:02,222 --> 03:44:08,095 CANNOT REPLACE THE FIBERS 3729 03:44:08,095 --> 03:44:16,703 INSTEAD OF INTERSTITIAL FIBROSIS 3730 03:44:16,703 --> 03:44:19,706 WE CAN REVERSE INTERSTITIAL 3731 03:44:19,706 --> 03:44:20,307 FIBERS AND THE FIRST MEANS IS 3732 03:44:20,307 --> 03:44:28,415 SURGERY. 3733 03:44:28,415 --> 03:44:35,122 WE WENT FOR OUR DATA AND APPLIED 3734 03:44:35,122 --> 03:44:40,694 MACHINE LEARNING TO CLASSIFY THE 3735 03:44:40,694 --> 03:44:45,699 PATIENTS IN FOUR PHENOGROUPS AND 3736 03:44:45,699 --> 03:44:50,237 THE MODEL USED ONLY THREE 3737 03:44:50,237 --> 03:44:53,140 PARAMETERS AND THE DEGREE OF 3738 03:44:53,140 --> 03:44:55,375 MODELLING AND THE VALUE OF 3739 03:44:55,375 --> 03:45:01,481 STRAIN WHICH IS A MARKER OF 3740 03:45:01,481 --> 03:45:05,118 DIASTOLIC FUNCTION. 3741 03:45:05,118 --> 03:45:09,389 THE PHENOGROUP 4 HAD AN 3742 03:45:09,389 --> 03:45:12,292 INCREASED PREVALENCE OF THE F 3743 03:45:12,292 --> 03:45:14,394 FIBERS IN THE PATIENTS AND RISK 3744 03:45:14,394 --> 03:45:16,696 OF CARDIOVASCULAR EVENTS DURING 3745 03:45:16,696 --> 03:45:16,963 FOLLOW-UP. 3746 03:45:16,963 --> 03:45:25,505 YOU CAN SEE ON THE GRAPH 3747 03:45:25,505 --> 03:45:34,181 PATIENTS AND 50% RATE OF FOLLOW 3748 03:45:34,181 --> 03:45:39,052 UP WHICH MEANS THE MODEL IS 3749 03:45:39,052 --> 03:45:41,655 WORKING VERY WELL. 3750 03:45:41,655 --> 03:45:43,790 AND THEY CAN PREDICT 3751 03:45:43,790 --> 03:45:47,527 CARDIOVASCULAR OUTCOME WHICH IS 3752 03:45:47,527 --> 03:45:48,395 IMPRESSIVE AND SO IN MACHINE 3753 03:45:48,395 --> 03:45:50,330 LEARNING CAN IMPROVE OR SIMPLIFY 3754 03:45:50,330 --> 03:45:51,431 OUR APPROACH OF PATIENTS. 3755 03:45:51,431 --> 03:45:54,968 I DON'T MEAN WE HAVE TO APPLY 3756 03:45:54,968 --> 03:46:01,741 DIRECTLY THE MODEL TO CLINICAL 3757 03:46:01,741 --> 03:46:12,285 PRACTICE BUT VERY INTERESTING TO 3758 03:46:18,291 --> 03:46:21,394 RAISE THIS AND BY A PREVIOUS 3759 03:46:21,394 --> 03:46:23,263 SPEAKER THEY ARE SPOKE ABOUT THE 3760 03:46:23,263 --> 03:46:28,135 WITH 500 PATIENTS WITH PROLAPSE 3761 03:46:28,135 --> 03:46:29,336 AND DYSFUNCTION. 3762 03:46:29,336 --> 03:46:35,175 AND THEY ARE USED DIFFERENT 3763 03:46:35,175 --> 03:46:37,444 PARAMETERS OR WEARABLES TO 3764 03:46:37,444 --> 03:46:38,512 CLASSIFY THE PATIENTS RAND THE 3765 03:46:38,512 --> 03:46:41,515 SEVERITY OF THE PROLAPSE AND THE 3766 03:46:41,515 --> 03:46:44,384 DEGREE OF RIGHT VENTRICULAR 3767 03:46:44,384 --> 03:46:46,486 REMODELLING AND THE DEGREE OF 3768 03:46:46,486 --> 03:46:52,125 MODELLING AND THE PRESENCE OF 3769 03:46:52,125 --> 03:47:02,435 FIBERS AND PRESENCE OF THIS AND 3770 03:47:02,435 --> 03:47:12,579 WE HAD TACHYCARDIA AND STRATIFY 3771 03:47:12,579 --> 03:47:15,282 PATIENT TO TWO SUB GROUPS. 3772 03:47:15,282 --> 03:47:20,320 THE MORE SEVERE PHENOTYPE AND 3773 03:47:20,320 --> 03:47:21,421 LOW RISK PHENOTYPE. 3774 03:47:21,421 --> 03:47:23,356 THE PAPER IS INTERESTING BECAUSE 3775 03:47:23,356 --> 03:47:27,761 THIS POPULATION IS VERY LOW RISK 3776 03:47:27,761 --> 03:47:31,064 POPULATION, NO PARTICULAR 3777 03:47:31,064 --> 03:47:32,432 DYSFUNCTION ONLY MITRAL VALVE 3778 03:47:32,432 --> 03:47:37,037 MITRAL VALVE EXPLORED WITH 3779 03:47:37,037 --> 03:47:40,540 RESONANCE IMAGING TO AND 3780 03:47:40,540 --> 03:47:41,208 FIBRO 3781 03:47:41,208 --> 03:47:51,384 FIBROSIS. 3782 03:47:53,453 --> 03:47:56,690 PATIENTS OF ARE FOURFOLD 3783 03:47:56,690 --> 03:48:02,162 INCREASE AND RISK AT DEVELOPING 3784 03:48:02,162 --> 03:48:06,866 SEVERE OR LIFE-THREATENING STEEZ 3785 03:48:06,866 --> 03:48:08,768 AND THE NUMBER OF EVENTS IS VERY 3786 03:48:08,768 --> 03:48:14,908 LOW ONLY 18 EVENTS DURING FIVE 3787 03:48:14,908 --> 03:48:17,177 YEAR FOLLOW UP AND HAVE TO ADD 3788 03:48:17,177 --> 03:48:21,248 MORE PATIENTS AND LONGER 3789 03:48:21,248 --> 03:48:24,684 FOLLOW-UP TO DECIDE IF THE 3790 03:48:24,684 --> 03:48:26,386 DIFFERENT PARAMETERS FOUND BY 3791 03:48:26,386 --> 03:48:27,854 THE MACHINE LEARNING METHOD OR 3792 03:48:27,854 --> 03:48:29,789 MODEL IS ACCURATE TO BE APPLIED 3793 03:48:29,789 --> 03:48:37,497 IN THE CLINICAL PRACTICE. 3794 03:48:37,497 --> 03:48:39,633 TO FINISH I WANT TO HIGHLIGHT 3795 03:48:39,633 --> 03:48:48,942 THE NICE PAPER FROM THE TEAM OF 3796 03:48:48,942 --> 03:48:51,111 FRANCESCA DELLING AND I USED A 3797 03:48:51,111 --> 03:48:53,113 SIMPLE ECG AND THE COMPUTER 3798 03:48:53,113 --> 03:48:54,180 ANALYZED A DIFFERENT PART IN 3799 03:48:54,180 --> 03:48:59,519 BLUE HERE AND SO WE CANNOT SEE 3800 03:48:59,519 --> 03:49:03,823 THIS BUT THE MACHINE LEARNING 3801 03:49:03,823 --> 03:49:06,226 MODEL WAS ABLE TO SEE SOMETHING 3802 03:49:06,226 --> 03:49:10,163 AND IDENTIFY THIS IN THE PATIENT 3803 03:49:10,163 --> 03:49:11,931 AND THE PRESENCE OF FIBROSIS AND 3804 03:49:11,931 --> 03:49:18,605 PREDICT THE OUTCOME OF THE 3805 03:49:18,605 --> 03:49:19,873 PATIENT. 3806 03:49:19,873 --> 03:49:27,414 YOU CAN SEE THE METHOD CAN GO 3807 03:49:27,414 --> 03:49:33,520 OVER OUR LIMITATION AND IT'S 3808 03:49:33,520 --> 03:49:35,789 DIFFICULT TO BE VERY COMPETENT 3809 03:49:35,789 --> 03:49:38,358 WHERE WE CAN'T SEE WHAT THE 3810 03:49:38,358 --> 03:49:42,262 MACHINE LEARNING MODEL IS 3811 03:49:42,262 --> 03:49:42,896 ANALYZING. 3812 03:49:42,896 --> 03:49:44,397 MAYBE IN THE FUTURE WE'LL USE 3813 03:49:44,397 --> 03:49:48,868 ECG TO TREAT OUR PATIENTS 3814 03:49:48,868 --> 03:49:53,173 WITHOUT THIS AND I'LL TWO TO THE 3815 03:49:53,173 --> 03:49:56,643 PAGE. 3816 03:49:56,643 --> 03:49:58,044 TO CONCLUDE THE INTELLIGENCE 3817 03:49:58,044 --> 03:50:06,853 APPLIED TO THE CMR CAN IMPROVE 3818 03:50:06,853 --> 03:50:08,121 THE DIAGNOSIS OF SEVERITY AND 3819 03:50:08,121 --> 03:50:09,889 THOSE MOST AT RISK. 3820 03:50:09,889 --> 03:50:12,525 ARTIFICIAL INTELLIGENCE IS A 3821 03:50:12,525 --> 03:50:16,896 VALUABLE TOOL TO CLUSTER 3822 03:50:16,896 --> 03:50:19,599 PATIENTS WITH MVP AND 3823 03:50:19,599 --> 03:50:21,434 INTERVENTIONS NOT KNOWN IN THE 3824 03:50:21,434 --> 03:50:22,268 CLINICAL SETTING. 3825 03:50:22,268 --> 03:50:26,439 ARTIFICIAL INTELLIGENCE MAY 3826 03:50:26,439 --> 03:50:28,508 SIMPLIFY THE ALGORITHM USED IN 3827 03:50:28,508 --> 03:50:30,110 CLINICAL PRACTICE FOR IMPROVING 3828 03:50:30,110 --> 03:50:35,181 OUR CLINICAL DECISION MAKING 3829 03:50:35,181 --> 03:50:39,319 PROCESS BASED ON PATIENTS 3830 03:50:39,319 --> 03:50:41,855 CLUSTERING FOR EXAMPLE. 3831 03:50:41,855 --> 03:50:43,957 HOWEVER, MACHINE LEARNING NEEDS 3832 03:50:43,957 --> 03:50:47,160 TO TRAIN THE MODEL AND TO 3833 03:50:47,160 --> 03:50:49,396 VALIDATE THE FINAL MODEL AND TO 3834 03:50:49,396 --> 03:50:50,730 MONITOR THE MODEL. 3835 03:50:50,730 --> 03:50:56,169 SO IT IS NOT ONLY THE MACHINES 3836 03:50:56,169 --> 03:50:59,205 THAT WILL WORK WITHOUT. 3837 03:50:59,205 --> 03:51:05,178 AND TO CONCLUDE THE VALUE NEEDS 3838 03:51:05,178 --> 03:51:15,855 TO BE EXPLORED AND LOOKING AT 3839 03:51:20,960 --> 03:51:22,595 THE MITRAL VALVE PROLAPSE. 3840 03:51:22,595 --> 03:51:23,163 >> THANK YOU. 3841 03:51:23,163 --> 03:51:24,297 VERY INTRIGUING. 3842 03:51:24,297 --> 03:51:26,399 IT LOOKS LIKE THE BEACH BEHIND 3843 03:51:26,399 --> 03:51:26,599 YOU. 3844 03:51:26,599 --> 03:51:27,734 DOES ANYONE HAVE QUESTIONS OR 3845 03:51:27,734 --> 03:51:28,301 COMMENTS ON THE PARTICULAR 3846 03:51:28,301 --> 03:51:38,545 PRESENTATIONS? 3847 03:51:47,821 --> 03:51:49,522 >> IF THERE'S NO QUESTIONS, 3848 03:51:49,522 --> 03:51:59,833 THANK YOU SO MUCH. 3849 03:52:01,568 --> 03:52:03,470 >> JUST ONE. 3850 03:52:03,470 --> 03:52:06,039 EXCELLENT TALK. 3851 03:52:06,039 --> 03:52:10,243 THE ISSUE IS PEOPLE PUT 3852 03:52:10,243 --> 03:52:10,910 ARTIFICIAL INTELLIGENCE IN THE 3853 03:52:10,910 --> 03:52:15,815 PAPER TO GET IT PUBLISHED. 3854 03:52:15,815 --> 03:52:18,251 BUT WHEN YOU SEE PEOPLE 3855 03:52:18,251 --> 03:52:18,852 PUBLISHING ARTIFICIAL 3856 03:52:18,852 --> 03:52:19,953 INTELLIGENCE ON 18 EVENTS YOU 3857 03:52:19,953 --> 03:52:22,956 SAY I MAY NOT HAVE TO SEE THIS 3858 03:52:22,956 --> 03:52:23,256 PAPER. 3859 03:52:23,256 --> 03:52:29,829 IT MAY -- WE MAY WANT TO MAKE IT 3860 03:52:29,829 --> 03:52:30,096 DISAPPEAR. 3861 03:52:30,096 --> 03:52:32,565 SO IT'S -- WHAT IS THE 3862 03:52:32,565 --> 03:52:36,936 UTILIZATION THAT WILL ALLOW TO 3863 03:52:36,936 --> 03:52:42,442 EXTEND OUR VIEW TO DETECT THE 3864 03:52:42,442 --> 03:52:43,109 PATIENTS WITH MITRAL VALVE 3865 03:52:43,109 --> 03:52:45,512 PROLAPSE EVEN JUST MITRAL VALVE 3866 03:52:45,512 --> 03:52:49,115 PROLAPSE IN THE POPULATION? 3867 03:52:49,115 --> 03:52:54,120 AND FACILITATE OUR WORK ON THESE 3868 03:52:54,120 --> 03:52:54,687 PATIENTS? 3869 03:52:54,687 --> 03:53:05,064 >> THANK YOU SO MUCH. 3870 03:53:07,033 --> 03:53:16,609 I DIDN'T SEE A MODEL BUT I THINK 3871 03:53:16,609 --> 03:53:20,513 MODELS OF MODELLING WILL BE TO 3872 03:53:20,513 --> 03:53:26,319 LEARN HOW TO DIAGNOSIS THE 3873 03:53:26,319 --> 03:53:26,920 MITRAL VALVE PROLAPSE AND WE 3874 03:53:26,920 --> 03:53:33,026 NEED TO DO THAT. 3875 03:53:33,026 --> 03:53:34,961 WE NEED TO PUT A LOT IMAGES IN 3876 03:53:34,961 --> 03:53:40,199 THE MODEL WITH DIFFERENT TYPES 3877 03:53:40,199 --> 03:53:44,370 OF MITRAL VALVE PROLAPSE TO 3878 03:53:44,370 --> 03:53:47,240 EXPLAIN TO THE MACHINE IT'S 3879 03:53:47,240 --> 03:53:48,274 MITRAL VALVE PROLAPSE AND 3880 03:53:48,274 --> 03:53:48,908 WITHOUT MITRAL VALVE PROLAPSE 3881 03:53:48,908 --> 03:53:52,211 AND AT THE END THE DEEP LEARNING 3882 03:53:52,211 --> 03:53:55,415 METHOD WILL BE ABLE TO LEARN AND 3883 03:53:55,415 --> 03:53:57,350 DIAGNOSE THE MACHINE LEARNING. 3884 03:53:57,350 --> 03:54:03,856 IT'S A VERY DIFFICULT FIELD OF 3885 03:54:03,856 --> 03:54:07,360 DEVELOPMENT BECAUSE AS YOU KNOW 3886 03:54:07,360 --> 03:54:09,529 MAYBE MACHINE LEARNING MODELS 3887 03:54:09,529 --> 03:54:11,798 ARE ABLE TO DIAGNOSIS WITH ALL 3888 03:54:11,798 --> 03:54:16,302 THE PICTURE YOU HAVE IN THE 3889 03:54:16,302 --> 03:54:18,438 IMAGE AND CAN MAKE MISTAKES WITH 3890 03:54:18,438 --> 03:54:23,176 THE DIFFERENT PIXELS ASSOCIATED 3891 03:54:23,176 --> 03:54:24,811 WITH THE DISEASE AND FOR EXAMPLE 3892 03:54:24,811 --> 03:54:27,380 IN THE PAST YOU PUT SOME ANIMALS 3893 03:54:27,380 --> 03:54:29,882 IN THE SNOW AND MACHINE LEARNING 3894 03:54:29,882 --> 03:54:31,851 MODEL WAS ABLE TO DIAGNOSIS OR 3895 03:54:31,851 --> 03:54:34,487 IDENTIFY THE ANIMAL IN THE SNOW. 3896 03:54:34,487 --> 03:54:37,557 BUT WITHOUT SNOW IT WAS NOT ABLE 3897 03:54:37,557 --> 03:54:41,961 TO IDENTIFY THE SAME ANIMAL. 3898 03:54:41,961 --> 03:54:43,663 THE DNA IS ALSO IMPORTANT. 3899 03:54:43,663 --> 03:54:46,866 IT'S WHY IT IS VERY IMPORTANT TO 3900 03:54:46,866 --> 03:54:51,004 HAVE A COHORT FROM ANOTHER 3901 03:54:51,004 --> 03:54:53,006 INSTITUTION WITH DIFFERENT 3902 03:54:53,006 --> 03:54:58,478 SETTINGS OF IMAGES TO TEST THE 3903 03:54:58,478 --> 03:55:01,514 MODEL OF MACHINE LEARNING. 3904 03:55:01,514 --> 03:55:02,448 >> THE REPRESENTATION STILL 3905 03:55:02,448 --> 03:55:02,682 VALID. 3906 03:55:02,682 --> 03:55:05,551 IT DEPENDS ON THE INTERPRETATION 3907 03:55:05,551 --> 03:55:11,524 OF THE DIAGNOSIS ON THE CONTEXT. 3908 03:55:11,524 --> 03:55:12,125 >> YES. 3909 03:55:12,125 --> 03:55:17,130 AND DIAGNOSIS WITH THE 3910 03:55:17,130 --> 03:55:18,998 CARDIOLOGIST BUT IT WILL HELP 3911 03:55:18,998 --> 03:55:22,368 PHYSICIAN IN ONCOLOGY FOR SURE 3912 03:55:22,368 --> 03:55:25,505 AND IN HEMATOLOGY AND PROBABLY 3913 03:55:25,505 --> 03:55:31,144 IN CARDIOLOGY. 3914 03:55:31,144 --> 03:55:40,286 >> 3915 03:55:40,286 --> 03:55:43,122 >> I HAVE A QUICK COMMENT ON OUR 3916 03:55:43,122 --> 03:55:45,625 WORK AND WE HAVE PATIENTS WHO 3917 03:55:45,625 --> 03:55:48,561 ARE ASYMPTOMATIC AND THEN WE 3918 03:55:48,561 --> 03:55:52,198 FIND OUT A PATIENT HAD A CARDIAC 3919 03:55:52,198 --> 03:55:54,100 ARREST THAT WAS COMPLETELY 3920 03:55:54,100 --> 03:55:56,202 ASYMPTOMATIC SO MAYBE WE SHOULD 3921 03:55:56,202 --> 03:56:00,173 MONITOR THE PATIENTS AND AN EKG 3922 03:56:00,173 --> 03:56:02,108 IS ROUTINE DONE CHEAP CAN MAYBE 3923 03:56:02,108 --> 03:56:04,844 TELL US THE PATIENT NEEDS AT 3924 03:56:04,844 --> 03:56:05,611 LEAST AMBULATORY MONITORING. 3925 03:56:05,611 --> 03:56:08,047 WE DON'T KNOW THE INTEGRAL WE 3926 03:56:08,047 --> 03:56:10,249 SHOULD USE FOR THE MONITORS. 3927 03:56:10,249 --> 03:56:13,119 IF WE GET ONE THERE'S NO 3928 03:56:13,119 --> 03:56:16,622 ACTIVITY ON ONE MONITOR AND WHAT 3929 03:56:16,622 --> 03:56:20,593 ABOUT PROGRESSION OF ECTOPY. 3930 03:56:20,593 --> 03:56:24,597 THE CLASSIFICATION IS TO FIT THE 3931 03:56:24,597 --> 03:56:26,132 ASYMPTOMATIC PATIENTS WHO MAY 3932 03:56:26,132 --> 03:56:36,676 NEED MORE AMBULATORY MONITORING. 3933 03:56:38,411 --> 03:56:40,513 >> IMPRESSIVE WORK. 3934 03:56:40,513 --> 03:56:41,981 THANK YOU FOR THE PUBLICATION. 3935 03:56:41,981 --> 03:56:43,282 I'M INTERESTED TO GET THE MODEL, 3936 03:56:43,282 --> 03:56:53,426 PLEASE. 3937 03:56:54,927 --> 03:57:01,300 I WILL SPEND MORE TIME ON THE 3938 03:57:01,300 --> 03:57:02,635 ECHOCARDIOGRAPHY OR SEND THEM TO 3939 03:57:02,635 --> 03:57:03,002 EMR. 3940 03:57:03,002 --> 03:57:06,839 >> WE DIDN'T HAVE A VALIDATION 3941 03:57:06,839 --> 03:57:09,809 CORE FOR THE PAPER SO THAT WOULD 3942 03:57:13,579 --> 03:57:14,247 BE GREAT. 3943 03:57:14,247 --> 03:57:20,353 >> PALPITATIONS IS A SYMPTOM 3944 03:57:20,353 --> 03:57:22,021 PATIENTS ARE AWARE OF. 3945 03:57:22,021 --> 03:57:27,026 I COULDN'T AGREE IF YOU HAVE 3946 03:57:27,026 --> 03:57:28,327 DOCUMENTED MITRAL VALVE DISEASE 3947 03:57:28,327 --> 03:57:34,967 AND EXPERIENCED PALPITATIONS 3948 03:57:34,967 --> 03:57:35,768 LIKE WE BUY OUR WRIST BLOOD 3949 03:57:35,768 --> 03:57:38,871 PRESSURE CUFF CAN FOR $99 NOW 3950 03:57:38,871 --> 03:57:41,374 YOU CAN BUY SOPHISTICATED 3951 03:57:41,374 --> 03:57:49,515 DEVICES TO DO AN EKG AND EASILY 3952 03:57:49,515 --> 03:57:56,656 AND TRANSLATE IT TO THE CLOUD 3953 03:57:56,656 --> 03:57:58,591 FOR THE SAME AMOUNT OF MONEY AND 3954 03:57:58,591 --> 03:58:04,363 UNDERSTANDING PAL PPITATIONS AN 3955 03:58:04,363 --> 03:58:06,566 WHAT THEY MEAN AND ARRHYTHMIA IS 3956 03:58:06,566 --> 03:58:12,471 QUITE INTERESTING. 3957 03:58:12,471 --> 03:58:14,307 GREAT TOPIC IN TERMS OF FUTURE 3958 03:58:14,307 --> 03:58:15,141 RESEARCH TO THINK ABOUT. 3959 03:58:15,141 --> 03:58:16,175 >> THANK YOU. 3960 03:58:16,175 --> 03:58:20,379 THERE WAS A PRIOR PAPER USING 3961 03:58:20,379 --> 03:58:23,015 EKG TRYING TO DETECT PROLAPSE 3962 03:58:23,015 --> 03:58:25,818 AND THE PERFORMANCE OF THE MODEL 3963 03:58:25,818 --> 03:58:29,188 WAS NOT AS GOOD AS OPPOSED TO 3964 03:58:29,188 --> 03:58:31,457 ARRHYTHMIC PROLAPSE. 3965 03:58:31,457 --> 03:58:35,528 WE'RE PICKING UP AN ELECTRICAL 3966 03:58:35,528 --> 03:58:40,733 PHENOMENON WHERE WE PICK UP 3967 03:58:40,733 --> 03:58:42,268 ARRHYTHMIC PROLAPSE SO IT WAS 3968 03:58:42,268 --> 03:58:42,902 DIFFERENT IN DETECTION OF MVP 3969 03:58:42,902 --> 03:58:45,905 ALONE. 3970 03:58:45,905 --> 03:58:46,973 >> THANK YOU VERY MUCH. 3971 03:58:46,973 --> 03:58:47,907 WE'LL HAVE A FEW MORE MINUTES 3972 03:58:47,907 --> 03:58:49,508 FOR DISCUSSION AT THE END OF THE 3973 03:58:49,508 --> 03:58:49,976 SESSION. 3974 03:58:49,976 --> 03:58:52,445 I'D LIKE TO MOVE ALONG NOW TO 3975 03:58:52,445 --> 03:59:02,989 THE NEXT SPEAKER, FARAH SHEIKH 3976 03:59:03,322 --> 03:59:04,323 FROM THE UNIVERSITY OF 3977 03:59:04,323 --> 03:59:05,191 CALIFORNIA SAN DIEGO. 3978 03:59:05,191 --> 03:59:11,530 >> I'M COMING FROM AN OUT OF BOX 3979 03:59:11,530 --> 03:59:11,764 FIELD. 3980 03:59:11,764 --> 03:59:22,241 I WORK ON ARRHYTHMIC GENIC 3981 03:59:26,913 --> 03:59:28,414 CARDIOMYOPATHY WHICH MAY HAVE 3982 03:59:28,414 --> 03:59:29,682 POTENTIAL TO TRANSLATE TO MVP AS 3983 03:59:29,682 --> 03:59:39,792 WELL. 3984 03:59:59,111 --> 04:00:01,514 ARRHYTHMOGENIC RISK AND SOME 3985 04:00:01,514 --> 04:00:03,316 HAVE MORE SERIOUS RISK. 3986 04:00:03,316 --> 04:00:05,251 ONE SUB TYPE IS THE BARLOW'S 3987 04:00:05,251 --> 04:00:08,387 DISEASE AND PATIENTS ARE YOUNGER 3988 04:00:08,387 --> 04:00:12,091 AND THEY'RE THE ONES WITH THE 3989 04:00:12,091 --> 04:00:17,229 MOST OR HIGHEST ARRHYTHMIC RISK 3990 04:00:17,229 --> 04:00:19,298 AND THERE'S STILL A RISK BUT NOT 3991 04:00:19,298 --> 04:00:23,669 ADDS HIGH AS BARLOW'S. 3992 04:00:23,669 --> 04:00:26,439 IT GOES TO IMPROVE THE PATIENT 3993 04:00:26,439 --> 04:00:32,511 OUTCOME AND GUIDE THERAPEUTIC 3994 04:00:32,511 --> 04:00:33,346 DESIGNS AND ARRHYTHMIC RISK IN 3995 04:00:33,346 --> 04:00:33,980 THE POPULATION AND MY TAKE ON 3996 04:00:33,980 --> 04:00:44,056 IT. 3997 04:00:44,924 --> 04:00:47,693 THERE'S CLEARLY A RISK OF SUDDEN 3998 04:00:47,693 --> 04:00:52,531 DEATH AND THREEFOLD HIGHER THAN 3999 04:00:52,531 --> 04:00:58,404 THE GENERAL POPULATION AND 4% OF 4000 04:00:58,404 --> 04:01:01,907 DEATHS ARE AMONG YOUNG ATHLETES. 4001 04:01:01,907 --> 04:01:05,211 WE TALKED ABOUT THE RISK 4002 04:01:05,211 --> 04:01:08,447 ARRHYTHMOGENIC RISK FACTORS AND 4003 04:01:08,447 --> 04:01:11,217 LEAFLET THICKNESS AND BEAUTIFUL 4004 04:01:11,217 --> 04:01:14,887 TALKS ABOUT FIBROSIS AND 4005 04:01:14,887 --> 04:01:15,888 VENTRICULAR MYOPATHY AND 4006 04:01:15,888 --> 04:01:19,592 CLINICAL MARKERS EXPLAIN ONLY 4007 04:01:19,592 --> 04:01:21,494 PARTIALLY WHO IS AT RISK. 4008 04:01:21,494 --> 04:01:24,063 UNFORTUNATELY MVPs ARE BENIGN OR 4009 04:01:24,063 --> 04:01:27,333 AS I'LL REFER TO THEM AS 4010 04:01:27,333 --> 04:01:28,401 CONCEALED AND IT ONLY LIES 4011 04:01:28,401 --> 04:01:30,403 WITHIN A SUBSET OF PATIENTS WITH 4012 04:01:30,403 --> 04:01:33,439 UNIQUE FEATURES LIKE MAD WHICH 4013 04:01:33,439 --> 04:01:35,341 IS DIFFICULT TO DETECT USING 4014 04:01:35,341 --> 04:01:38,644 STANDARD CLINICAL IMAGING AND 4015 04:01:38,644 --> 04:01:45,051 REQUIRES ADVANCED TECHNIQUES. 4016 04:01:45,051 --> 04:01:48,554 SO WHEN I LOOK AT THE GENETIC 4017 04:01:48,554 --> 04:01:53,259 BASIS OF THIS STEEZ -- DISEASE 4018 04:01:53,259 --> 04:01:54,827 AND COMING FROM A RARE DISEASE 4019 04:01:54,827 --> 04:01:57,129 PERSPECTIVE AND WE DON'T HAVE A 4020 04:01:57,129 --> 04:01:58,064 LOT OF TO WORK WITH AND 4021 04:01:58,064 --> 04:01:59,598 SOMETIMES HAVE TO BE CREATIVE IN 4022 04:01:59,598 --> 04:02:02,802 WHAT YOU'RE LOOKING AT AND 4023 04:02:02,802 --> 04:02:11,243 PATTERN AND WHAT DRIVES 4024 04:02:11,243 --> 04:02:13,946 COMMONALITIES AND WITH FAMILIAL 4025 04:02:13,946 --> 04:02:16,348 STUDIES THERE'S SOME SORT OF 4026 04:02:16,348 --> 04:02:19,919 AUTO SOMAL DOMINANT PATTERN AND 4027 04:02:19,919 --> 04:02:20,953 AGE-DEPENDENT PENETRANTS BUT 4028 04:02:20,953 --> 04:02:25,357 MANY ARE LINKED TO THE CELL-CELL 4029 04:02:25,357 --> 04:02:27,993 AND CYTOSKELETAL COMPONENTS FROM 4030 04:02:27,993 --> 04:02:32,731 THE CARDY MYOPATHY SPACE I'M IN. 4031 04:02:32,731 --> 04:02:43,275 DCH AS ONE IS PART OF THE SAME 4032 04:02:44,210 --> 04:02:44,376 FAMILY. 4033 04:02:44,376 --> 04:02:48,747 WHEN WE TALK ABOUT CELL-CELL 4034 04:02:48,747 --> 04:02:50,282 FUNCTION IN CARDIAC MUSCLE 4035 04:02:50,282 --> 04:02:55,287 THERE'S THREE TYPES AND ONE ARE 4036 04:02:55,287 --> 04:02:58,290 FASCIA LINKED TO ACTIN AND I SEE 4037 04:02:58,290 --> 04:03:06,065 A LOT RELATED TO FILAMENT C AND 4038 04:03:06,065 --> 04:03:13,439 DZIB PART OF THE MICRO TUBULE 4039 04:03:13,439 --> 04:03:16,876 FUNCTION AND ALPK3 AND A LOT OF 4040 04:03:16,876 --> 04:03:19,812 THE PROTEIN-PROTEIN INTERACTS 4041 04:03:19,812 --> 04:03:22,915 THAT FORMULATE AND FORM A LOT OF 4042 04:03:22,915 --> 04:03:25,017 THE DISEASES THAT I'M STUDYING 4043 04:03:25,017 --> 04:03:27,586 IN TERMS OF THE CARDIOMYOPATHY 4044 04:03:27,586 --> 04:03:27,820 SPACE. 4045 04:03:27,820 --> 04:03:30,523 THEY ARE CONVERGE TO ME AT THIS 4046 04:03:30,523 --> 04:03:33,692 JUNCTURE OF THE CELL-CELL 4047 04:03:33,692 --> 04:03:34,293 ADHESION. 4048 04:03:34,293 --> 04:03:42,968 AND SPTBN1 PART OF THE BETA 2 4049 04:03:42,968 --> 04:03:50,376 SPECTRIN CONNECTS SO AND WHAT 4050 04:03:50,376 --> 04:03:54,680 JUMPED OUT TO ME WHEN I LOOKED 4051 04:03:54,680 --> 04:03:56,415 AT THE SMALL SET OF GENES. 4052 04:03:56,415 --> 04:04:03,622 I FEEL THERE'S A LOT OF PRAYER 4053 04:04:03,622 --> 04:04:07,526 -- PARALLELS. 4054 04:04:07,526 --> 04:04:08,194 ARRHYTHMOGENIC CARDIOMYOPATHY IS 4055 04:04:08,194 --> 04:04:11,263 COMPLEX AND DEFINED BY A RIGHT 4056 04:04:11,263 --> 04:04:13,499 HEART DISEASE BUT MORE AND MORE 4057 04:04:13,499 --> 04:04:18,571 STUDIES SUGGEST THE LEFT HEART 4058 04:04:18,571 --> 04:04:20,573 OR BIVENTRICULAR INVOLVEMENT AND 4059 04:04:20,573 --> 04:04:22,441 IN THE EARLY STAGE OF THE 4060 04:04:22,441 --> 04:04:28,080 DISEASE WHERE ELECTRICAL ISSUES 4061 04:04:28,080 --> 04:04:29,582 THERE'S NO STRUCTURAL PROBLEM 4062 04:04:29,582 --> 04:04:32,384 WITH THE HEART BUT CAN HAVE 4063 04:04:32,384 --> 04:04:33,485 SUDDEN DEATH AND CAN BE MADE 4064 04:04:33,485 --> 04:04:34,186 WORSE WITH EXERCISE. 4065 04:04:34,186 --> 04:04:38,624 WHEN YOU LOOK AT PATIENTS WHO 4066 04:04:38,624 --> 04:04:41,260 DIE OF HEART FAILURE THREES 4067 04:04:41,260 --> 04:04:44,396 CLEARLY A STRUCTURAL COMPONENT 4068 04:04:44,396 --> 04:04:47,199 AND CARDIAC MUSCLE CELL DEATH 4069 04:04:47,199 --> 04:04:48,701 AND LESS RED MUSCLE IN THE 4070 04:04:48,701 --> 04:04:50,536 AUTOPSIED HEART AND SCARRING, 4071 04:04:50,536 --> 04:04:53,906 WHICH IS BLUE AND THE CIRCULAR 4072 04:04:53,906 --> 04:05:04,416 CELLS WHICH ARE ACTUALLY FAT. 4073 04:05:08,587 --> 04:05:12,057 SIMILAR TO MVP IT CAN OCCUR 4074 04:05:12,057 --> 04:05:15,661 PRIOR TO THE TRANSITION TO SOME 4075 04:05:15,661 --> 04:05:16,929 OVERT STRUCTURAL ANOMALY AND THE 4076 04:05:16,929 --> 04:05:20,299 LATE ONSET IS ASSOCIATED WITH 4077 04:05:20,299 --> 04:05:22,668 SERIOUS CARDIAC ARREST SUCH AS 4078 04:05:22,668 --> 04:05:25,537 HEART FAILURE. 4079 04:05:25,537 --> 04:05:31,910 SO WHEN WE LOOK AT 4080 04:05:31,910 --> 04:05:32,578 ARRHYTHMOGENIC CARDIOMYOPATHY 4081 04:05:32,578 --> 04:05:33,979 IT'S PART OF THE CELL-CELL 4082 04:05:33,979 --> 04:05:36,015 FUNCTION AND LOOK AT THE HEART 4083 04:05:36,015 --> 04:05:37,783 AND ZOOM INTO A REGION OF THE 4084 04:05:37,783 --> 04:05:40,853 HEART THERE'S TWO MUSCLE CELLS 4085 04:05:40,853 --> 04:05:45,791 THAT LINK AND THREE COMPONENTS 4086 04:05:45,791 --> 04:05:48,627 AND THEY ESSENTIALLY ARE THE 4087 04:05:48,627 --> 04:05:50,963 MECHANICAL ANCHORS AND PREVENT 4088 04:05:50,963 --> 04:05:53,299 YOUR CELLS FROM RIPPING A PART 4089 04:05:53,299 --> 04:05:58,504 AND THERE'S THE GAP JUNCTIONS 4090 04:05:58,504 --> 04:06:00,372 THE ELECTRICAL CHANNELS AND 4091 04:06:00,372 --> 04:06:02,775 THOSE THAT CONNECT TO ACTIN. 4092 04:06:02,775 --> 04:06:05,878 WHEN YOU ZOOM INTO THE COMPLEX 4093 04:06:05,878 --> 04:06:09,615 THERE'S FIVE GENES AND THESE ARE 4094 04:06:09,615 --> 04:06:17,089 RIGHT IN THE MIDDLE, DESMOSOMES 4095 04:06:17,089 --> 04:06:20,159 AND IT'S LINKED TO THE 4096 04:06:20,159 --> 04:06:23,329 INTERMEDIATE FILAMENTS AND 40% 4097 04:06:23,329 --> 04:06:28,667 TO 50% ARE CONNECTED TO 4098 04:06:28,667 --> 04:06:33,505 AUTOSOMAL DEFICIENCIDEFICIENCIE. 4099 04:06:33,505 --> 04:06:42,181 IT DESTROYS THE WHOLE FUNCTION. 4100 04:06:42,181 --> 04:06:43,916 MOST THINK THERE'S NO THERAPY 4101 04:06:43,916 --> 04:06:45,217 BECAUSE YOU HAVE TO BRING THEM 4102 04:06:45,217 --> 04:06:47,853 ALL BACK AND A PARALLEL BETWEEN 4103 04:06:47,853 --> 04:06:52,358 MVP AND ACM IS THE MRAERJ GENES 4104 04:06:52,358 --> 04:06:54,226 ARE CONGREGATED OR ASSOCIATED 4105 04:06:54,226 --> 04:07:00,899 WITH THE CELL-CELL FUNCTION. 4106 04:07:00,899 --> 04:07:05,371 SO I FOCUSSED ONE OF THE MOST 4107 04:07:05,371 --> 04:07:08,407 PREVALENT MUTATIONS IN THE 4108 04:07:08,407 --> 04:07:10,976 DESMOSOMAL GENES FOR ACN. 4109 04:07:10,976 --> 04:07:15,114 THEY ACCOUNT FOR MORE THAN 70% 4110 04:07:15,114 --> 04:07:16,148 OF PATIENTS. 4111 04:07:16,148 --> 04:07:19,017 THESE MUTATIONS WHETHER 4112 04:07:19,017 --> 04:07:20,452 INSERTION, DELETIONS ARE THOUGHT 4113 04:07:20,452 --> 04:07:22,421 TO LEAD TO LOSS OF THE PROTEIN 4114 04:07:22,421 --> 04:07:23,956 AT THE CELL-CELL FUNCTION. 4115 04:07:23,956 --> 04:07:27,192 BUT WHEN I STARTED DIGGING INTO 4116 04:07:27,192 --> 04:07:29,395 IT, I THOUGHT THERE'S A LOT OF 4117 04:07:29,395 --> 04:07:33,732 EFFECTS WHERE AT THE RNA LEX 4118 04:07:33,732 --> 04:07:35,434 LEVEL BECAUSE THE TRANSCRIPT 4119 04:07:35,434 --> 04:07:36,769 LEVELS WERE DOWN REGULATED WITH 4120 04:07:36,769 --> 04:07:38,437 THE PATIENTS WITH THESE 4121 04:07:38,437 --> 04:07:43,542 MUTATIONS AND THE MUTATION FOR 4122 04:07:43,542 --> 04:07:47,413 P52 IS A RNA SPLICE SITE 4123 04:07:47,413 --> 04:07:47,679 MUTATION. 4124 04:07:47,679 --> 04:07:49,681 HIGHLIGHTING IT MAY BE A 4125 04:07:49,681 --> 04:07:50,849 CRITICAL MECHANISM TO GO AFTER 4126 04:07:50,849 --> 04:07:53,218 AND AT THE TIME THERE WERE NO 4127 04:07:53,218 --> 04:07:57,990 MECHANISTIC INSIGHTS IT'S HARD 4128 04:07:57,990 --> 04:07:59,291 TO UNDERSTAND HOW TO 4129 04:07:59,291 --> 04:08:00,392 THERAPEUTICALLY INTERVENE 4130 04:08:00,392 --> 04:08:03,462 BECAUSE YOU MAY GET A LARGER OR 4131 04:08:03,462 --> 04:08:04,763 SMALLER PRODUCT WHEN DEALING 4132 04:08:04,763 --> 04:08:06,298 WITH SPLICING TARGETS. 4133 04:08:06,298 --> 04:08:10,202 WE HYPOTHESIZED THE MUTATIONS 4134 04:08:10,202 --> 04:08:16,975 WERE SUFFICIENT TO TRIGGER 4135 04:08:16,975 --> 04:08:17,810 ARRHYTHMO 4136 04:08:17,810 --> 04:08:21,013 ARRHYTHMOGENIC CARDIOMYOPATHY 4137 04:08:21,013 --> 04:08:31,490 AND CIRCUMVENT THE DEFICITS. 4138 04:08:32,624 --> 04:08:34,827 THE NUMBER ONE MUTATION WAS A 4139 04:08:34,827 --> 04:08:37,663 SPLICE SITE MUTATION AND WE 4140 04:08:37,663 --> 04:08:39,198 GENERATED A CRISPR CAS KNOCK-IN 4141 04:08:39,198 --> 04:08:42,367 MOUSE WITH THE MUTATION. 4142 04:08:42,367 --> 04:08:46,839 AND I HEARD TWO HITS IN MVP AND 4143 04:08:46,839 --> 04:08:49,975 THAT'S ALSO THE CASE FOR ACM. 4144 04:08:49,975 --> 04:08:51,844 PATIENTS THE MOST SEVERE HAVE 4145 04:08:51,844 --> 04:08:55,681 TWO MUTATIONS OR ONE HIT AND 4146 04:08:55,681 --> 04:08:58,050 EXERCISE AND THAT DRIVES 4147 04:08:58,050 --> 04:08:58,317 SEVERITY. 4148 04:08:58,317 --> 04:09:02,955 WE SAW IN PATIENTS THAT THE 4149 04:09:02,955 --> 04:09:04,523 HOMOZYGOUS WITH TWO HITS AT THE 4150 04:09:04,523 --> 04:09:15,000 MORE SEVERE PREMATURE DEATH. 4151 04:09:17,569 --> 04:09:21,540 HETEROZYGOUS SHOWED LATER 4152 04:09:21,540 --> 04:09:21,974 EFFECT. 4153 04:09:21,974 --> 04:09:23,475 AND THROUGH SURFACE ANALYSIS WE 4154 04:09:23,475 --> 04:09:29,348 WERE ABLE TO SHOW TONS OF 4155 04:09:29,348 --> 04:09:32,050 ARRHYTHMIAS NOT FOUND IN THE 4156 04:09:32,050 --> 04:09:35,053 COUNTERPARTS OF THE MICE. 4157 04:09:35,053 --> 04:09:38,357 WE WERE ABLE TO SHOW THE 4158 04:09:38,357 --> 04:09:39,124 HISTOLOGICAL DEFICIT. 4159 04:09:39,124 --> 04:09:42,227 YOU CAN SEE FROM THE GROSS 4160 04:09:42,227 --> 04:09:45,531 MORPHOLOGY THE LEVEL OF FIBROSIS 4161 04:09:45,531 --> 04:09:49,001 THAT GOES ON IN THE HEARTS AND 4162 04:09:49,001 --> 04:09:50,035 THROUGH GENE EXPRESSION ANALYSIS 4163 04:09:50,035 --> 04:09:57,543 WERE ABLE TO SHOW UP REGULATED 4164 04:09:57,543 --> 04:10:00,112 COLLAGENS AND THE DEPOSITION IN 4165 04:10:00,112 --> 04:10:05,784 THE SUBCARDIUM OF THE RIGHT VENT 4166 04:10:05,784 --> 04:10:09,221 VENTRICLE AND SEE THE LIPID 4167 04:10:09,221 --> 04:10:10,289 DEPOSITION HIGHLIGHTING THE 4168 04:10:10,289 --> 04:10:13,458 MOUSE MODEL REALLY RECAPITULATES 4169 04:10:13,458 --> 04:10:17,462 THE HALLMARK OF THE DISEASE AS 4170 04:10:17,462 --> 04:10:26,471 SEEN IN THE PATIENTS. 4171 04:10:26,471 --> 04:10:29,308 WE WANTED TO LOOK AT THE 4172 04:10:29,308 --> 04:10:30,909 MECHANISM OF WHERE THE DRIVERS 4173 04:10:30,909 --> 04:10:31,109 LIE. 4174 04:10:31,109 --> 04:10:32,711 WHEN WE DID RNA ANALYSIS WE 4175 04:10:32,711 --> 04:10:35,414 FOUND IT RESULTED IN A HIGHER 4176 04:10:35,414 --> 04:10:37,015 PRODUCT WHICH WAS VERY LOW IN 4177 04:10:37,015 --> 04:10:37,249 LEVELS. 4178 04:10:37,249 --> 04:10:40,953 WHEN WE SEQUENCED IT WE FOUND IT 4179 04:10:40,953 --> 04:10:42,454 CAUSED PARTIAL INTRON RETENTION 4180 04:10:42,454 --> 04:10:45,390 BECAUSE IT SKIPPED OVER THE 4181 04:10:45,390 --> 04:10:47,059 SPLICE SITE MUTATED AND WENT 4182 04:10:47,059 --> 04:10:48,760 INTO THE INTRON AND RETAINED 4183 04:10:48,760 --> 04:10:50,996 PART OF IT. 4184 04:10:50,996 --> 04:10:56,068 AND AS A RESULT I'M SHOWING YOU 4185 04:10:56,068 --> 04:10:57,536 THE TWO HIGHER PRODUCTS AT VERY 4186 04:10:57,536 --> 04:11:01,540 LOW LEVELS AND YOU CAN SEE THE 4187 04:11:01,540 --> 04:11:12,184 DEFICITS AND THE YOU DESMOSOMAL 4188 04:11:22,995 --> 04:11:23,195 QUALITIES. 4189 04:11:23,195 --> 04:11:32,337 IS IT QUALITY OR QUANTITY. 4190 04:11:32,337 --> 04:11:34,806 WE DID AN EXPERIMENT AND CELLS 4191 04:11:34,806 --> 04:11:37,442 IN A DISH AND TOOK THE MYOCYTES 4192 04:11:37,442 --> 04:11:41,847 AND PUT THEM IN A DISH AND JUST 4193 04:11:41,847 --> 04:11:46,151 UP REGULATED THE WILD TYPE AND 4194 04:11:46,151 --> 04:11:47,819 MUTANT FORM AND WHAT WE SAW WAS 4195 04:11:47,819 --> 04:11:50,922 COMPARED NO THE UNINFECTED YOU 4196 04:11:50,922 --> 04:11:52,824 SEE THE BLANK SPACE BECAUSE ALL 4197 04:11:52,824 --> 04:11:54,359 THE GENES ARE DOWN REGULATED 4198 04:11:54,359 --> 04:11:57,529 WHETHER WE PUT THE WILD TYPE OR 4199 04:11:57,529 --> 04:11:58,964 THE MUTANT WE'RE ABLE TO 4200 04:11:58,964 --> 04:12:01,333 RESURRECT THE WHOLE COMPLEX. 4201 04:12:01,333 --> 04:12:03,368 IT JUST DIDN'T INCREASE THE 4202 04:12:03,368 --> 04:12:09,574 LEVEL OF PK 2 BUT ALL THE 4203 04:12:09,574 --> 04:12:12,678 PROTEINS ASSOCIATED WITH PK2 4204 04:12:12,678 --> 04:12:15,047 BECOME UP REGULATED HIGHLIGHTING 4205 04:12:15,047 --> 04:12:17,716 THERE'S A ONE FITS ALL THERE 4206 04:12:17,716 --> 04:12:23,522 COULD BE A SCAFFOLDING PROTEINS 4207 04:12:23,522 --> 04:12:26,224 IN TERMS OF PROTEINS, PROTEINS 4208 04:12:26,224 --> 04:12:26,591 INTERACTIONS. 4209 04:12:26,591 --> 04:12:29,361 THIS IS THE GENESIS FOR USING 4210 04:12:29,361 --> 04:12:32,230 GENE THERAPY AS A STRATEGY TO 4211 04:12:32,230 --> 04:12:33,565 CIRCUMVENT ACN IN OUR MOUSE 4212 04:12:33,565 --> 04:12:43,675 MODEL. 4213 04:12:45,644 --> 04:12:48,647 WE FIRST TRIED TO PREVENT THE 4214 04:12:48,647 --> 04:12:49,514 DISEASE AND LOOKED FOUR WEEKS 4215 04:12:49,514 --> 04:12:49,781 LATER. 4216 04:12:49,781 --> 04:12:52,184 YOU CAN SEE THE UNTREATED MICE 4217 04:12:52,184 --> 04:12:55,821 AT FOUR WEEKS WHERE ALL THESE 4218 04:12:55,821 --> 04:12:57,489 PROTEINS ARE DISASSOCIATED. 4219 04:12:57,489 --> 04:13:01,993 ON THE RIGHT SIDE YOU CAN SEE 4220 04:13:01,993 --> 04:13:06,531 WHEN WE RESURRECT OR INCREASE 4221 04:13:06,531 --> 04:13:09,468 ALL THE PROTEINS GET UP 4222 04:13:09,468 --> 04:13:11,236 REGULATED AGAIN AND THIS HAD A 4223 04:13:11,236 --> 04:13:12,771 HUGE EFFECT ON THE MORPHOLOGY OF 4224 04:13:12,771 --> 04:13:15,107 THE HEART IN C WHERE YOU CAN SEE 4225 04:13:15,107 --> 04:13:18,744 A VERY NORMAL LOOKING MUSCLE OR 4226 04:13:18,744 --> 04:13:24,449 HEART WHEN YOU COMPARE IT TO THE 4227 04:13:24,449 --> 04:13:26,418 CONTROLS. 4228 04:13:26,418 --> 04:13:28,720 ALSO COMPLETE PREVENTION OF 4229 04:13:28,720 --> 04:13:29,054 FIBROSIS. 4230 04:13:29,054 --> 04:13:31,590 IN H IF YOU LOOK AT THE SECOND 4231 04:13:31,590 --> 04:13:32,524 PANEL IN GREEN BARS WHERE THE 4232 04:13:32,524 --> 04:13:34,493 FUNCTION IS COMPARABLE TO THE 4233 04:13:34,493 --> 04:13:36,294 BLACK BARS AND GET COMPARABLE 4234 04:13:36,294 --> 04:13:38,930 FUNCTION AND ABSOLUTELY NO 4235 04:13:38,930 --> 04:13:41,466 ARRHYTHMIAS IN THE MICE AND YOU 4236 04:13:41,466 --> 04:13:44,035 CAN SEE THE MICE HAVE ABSOLUTELY 4237 04:13:44,035 --> 04:13:46,738 NO ARRHYTHMIAS AT THE TIME 4238 04:13:46,738 --> 04:13:46,938 POINT. 4239 04:13:46,938 --> 04:13:48,807 WE WANTED TO KNOW THE LONG-TERM 4240 04:13:48,807 --> 04:13:49,541 EFFECTS BECAUSE IT'S ONLY AT 4241 04:13:49,541 --> 04:13:59,751 FOUR WEEKS. 4242 04:14:01,052 --> 04:14:03,255 WE LET THEM GO FOR SIX MONTHS 4243 04:14:03,255 --> 04:14:04,723 AND THEY ARE SURVIVED AND NONE 4244 04:14:04,723 --> 04:14:06,825 OF THE UNTREATED MICE SURVIVED. 4245 04:14:06,825 --> 04:14:08,460 THE LEVEL OF THE CELL-CELL 4246 04:14:08,460 --> 04:14:10,395 FUNCTION ARE COMPARABLE TO 4247 04:14:10,395 --> 04:14:10,695 CONTROLS. 4248 04:14:10,695 --> 04:14:13,298 YOU COULD NEVER GET UNTREATED 4249 04:14:13,298 --> 04:14:15,433 MICE AT THIS POINT. 4250 04:14:15,433 --> 04:14:16,234 FUNCTION THROUGH MRI IS 4251 04:14:16,234 --> 04:14:17,803 COMPARABLE FOR THE LEFT AND 4252 04:14:17,803 --> 04:14:21,139 RIGHT SIDE. 4253 04:14:21,139 --> 04:14:25,577 ABSOLUTELY NO ARRHYTHMIAS IN THE 4254 04:14:25,577 --> 04:14:29,080 MICE BUT LOOKING AT PATIENTS 4255 04:14:29,080 --> 04:14:29,681 THEY'LL COME IN WITH EXISTING 4256 04:14:29,681 --> 04:14:37,656 STEEZ. 4257 04:14:37,656 --> 04:14:42,427 -- DISEASE AND WE USED THE 4258 04:14:42,427 --> 04:14:45,530 AAVPKP2 AND LOOKED TWO WEEKS 4259 04:14:45,530 --> 04:14:47,833 LATER AND SEE VIA WESTERN BLOT 4260 04:14:47,833 --> 04:14:50,435 WE CAN RESURRECT THE WHOLE 4261 04:14:50,435 --> 04:14:52,003 COMPLEX EVEN IN A DISEASE STATE 4262 04:14:52,003 --> 04:14:54,673 AND NOW IN D IF YOU LOOK AT THE 4263 04:14:54,673 --> 04:14:55,740 QUANTIFICATION OF THE MRI DATA 4264 04:14:55,740 --> 04:14:59,177 YOU CAN ALSO SEE IT IN SOME OF 4265 04:14:59,177 --> 04:15:00,779 THE REPRESENTATIVE IMAGES THAT 4266 04:15:00,779 --> 04:15:03,181 DIMENSIONS OF THE HEART ARE 4267 04:15:03,181 --> 04:15:05,817 SIGNIFICANTLY REDUCED AND WITH 4268 04:15:05,817 --> 04:15:09,788 TREATMENT AND FUNCTION STARTS TO 4269 04:15:09,788 --> 04:15:12,424 PULL AWAY FROM THE UNTREATED 4270 04:15:12,424 --> 04:15:14,059 CONTROLS WHICH ARE ONLY AT TWO 4271 04:15:14,059 --> 04:15:14,726 WEEKS. 4272 04:15:14,726 --> 04:15:18,296 SO WE ESSENTIALLY LEFT THESE 4273 04:15:18,296 --> 04:15:20,131 MICE TWO UNTIL 20 WEEKS AND 4274 04:15:20,131 --> 04:15:27,272 AGAIN 100% OF THE MICE SURVIVED 4275 04:15:27,272 --> 04:15:31,610 COMPARED TO 80% AT THE UNTREATED 4276 04:15:31,610 --> 04:15:34,713 MICE AND HIGHLIGHTS LATE 4277 04:15:34,713 --> 04:15:36,448 POST-NATAL RESTORATION RESCUES 4278 04:15:36,448 --> 04:15:37,515 THE DYSFUNCTION AND PROMOTES 4279 04:15:37,515 --> 04:15:44,856 SURVIVAL. 4280 04:15:44,856 --> 04:15:48,593 SO IN SUMMARY, WHAT I'VE SHOWN 4281 04:15:48,593 --> 04:15:51,529 IS THE SPLICE-SITE MUTATION 4282 04:15:51,529 --> 04:15:56,134 CAUSES AN EFFECT ON PROTEIN 4283 04:15:56,134 --> 04:15:58,036 QUALITY AND QUANTITY AND THE 4284 04:15:58,036 --> 04:15:58,904 MUTANT FORM IS THERE FOR PATIENT 4285 04:15:58,904 --> 04:16:00,238 TO SURVIVE. 4286 04:16:00,238 --> 04:16:03,341 AND IT HAS FUNCTIONALITY. 4287 04:16:03,341 --> 04:16:04,876 BUT CLEARLY IT'S NOT ESSENTIAL 4288 04:16:04,876 --> 04:16:08,446 OR IT CAN'T ALLOW THE HEART TO 4289 04:16:08,446 --> 04:16:08,680 THRIVE. 4290 04:16:08,680 --> 04:16:12,417 SO AS A RESULT YOU GET 4291 04:16:12,417 --> 04:16:13,051 DESMOSOMAL PROTEIN RESOLUTION 4292 04:16:13,051 --> 04:16:19,724 AND ALL THE CELL-CELL FUNCTION 4293 04:16:19,724 --> 04:16:23,528 DEFICIT WHICH IS DRIVE ALL THE 4294 04:16:23,528 --> 04:16:26,531 FEATURES AT THE HISTOAND 4295 04:16:26,531 --> 04:16:28,233 PHYSIOLOGIC LEVEL AND THE 4296 04:16:28,233 --> 04:16:31,870 STRATEGIES WITH THESE AS THE 4297 04:16:31,870 --> 04:16:33,538 GENE THERAPY HIGHLIGHT THE 4298 04:16:33,538 --> 04:16:35,340 RESIDENT SCAFFOLDING FUNCTION AT 4299 04:16:35,340 --> 04:16:37,275 THE DESMOSOME OR CELL-CELL 4300 04:16:37,275 --> 04:16:42,714 FUNCTION TO PREVENT AND RESCUE 4301 04:16:42,714 --> 04:16:44,783 CARDIAC DISEASE. 4302 04:16:44,783 --> 04:16:45,984 AT THIS POINT WE'RE EXCITED WITH 4303 04:16:45,984 --> 04:16:52,691 THE RESULT BUT YOU WANTED TO SEE 4304 04:16:52,691 --> 04:16:56,294 HOW TO COMMERCIALIZE THIS AS A 4305 04:16:56,294 --> 04:16:58,663 RESULT I STARTED A SPIN OFF FROM 4306 04:16:58,663 --> 04:17:05,804 THE LAB CALLED ARCV THERAPEUTICS 4307 04:17:05,804 --> 04:17:09,874 IN AUGUST 2018 AND WERE ACQUIRED 4308 04:17:09,874 --> 04:17:17,048 BY A NEW YORK STAGE CLINICAL 4309 04:17:17,048 --> 04:17:17,649 GENETIC MEDICINE COMPANY. 4310 04:17:17,649 --> 04:17:22,854 WE THEN WORKED TOGETHER WITH 4311 04:17:22,854 --> 04:17:26,891 THEM THEY ARE HAVE A PRODUCT 4312 04:17:26,891 --> 04:17:31,363 CALLED LX2020 TO TREAT PATIENTS 4313 04:17:31,363 --> 04:17:33,131 WITH ACM AND WERE ABLE TO SHOW 4314 04:17:33,131 --> 04:17:40,638 WITH THE PRODUCT WE WERE ABLE TO 4315 04:17:40,638 --> 04:17:50,582 IN DISEASED MICE ALLEVIATE THE 4316 04:17:50,582 --> 04:17:53,218 ARRHYTHMIA DELETATION AND 4317 04:17:53,218 --> 04:17:54,986 DYSFUNCTION AND THE WILL FDA 4318 04:17:54,986 --> 04:17:59,791 CLEARED TO TAKE IT AS A GENE 4319 04:17:59,791 --> 04:18:08,900 THERAPY FOR ARRHYTHMOGENIC 4320 04:18:08,900 --> 04:18:10,068 CARDIOMYOPATHY AND YOU CAN SEE 4321 04:18:10,068 --> 04:18:13,071 IN THE VEHICLE AND UNTREATED 4322 04:18:13,071 --> 04:18:16,074 MICE HOW YOU GET SEVERE DEFICIT 4323 04:18:16,074 --> 04:18:19,144 AND DYSFUNCTION OF THE 4324 04:18:19,144 --> 04:18:20,745 VENTRICLES IN THE HOMOZYGOUS 4325 04:18:20,745 --> 04:18:23,548 MICE BUT AS YOU INCREASE THE 4326 04:18:23,548 --> 04:18:27,485 DOSE OF PKP2 THE HIGH DOSE MICE 4327 04:18:27,485 --> 04:18:37,929 LOOK LIKE WILD TYPE MICE. 4328 04:18:40,632 --> 04:18:46,471 SO WE IDENTIFIED SPECIFIC 4329 04:18:46,471 --> 04:18:47,138 MOLECULAR TARGETS AND LED TO THE 4330 04:18:47,138 --> 04:18:50,208 TRIAL AND HAPPY TO REPORT WE 4331 04:18:50,208 --> 04:18:52,010 FINISHED ENROLLING AND DOSING 4332 04:18:52,010 --> 04:18:57,449 THE FIRST COHORT OF PATIENTS AND 4333 04:18:57,449 --> 04:18:59,150 PHASE 1/2 CLINICAL TRIAL AND 4334 04:18:59,150 --> 04:19:01,519 HOPE TO HAVE EXCITING RESULTS IN 4335 04:19:01,519 --> 04:19:03,288 THE NEW YEAR ON SAFETY AND BIO 4336 04:19:03,288 --> 04:19:08,359 DISTRIBUTION. 4337 04:19:08,359 --> 04:19:12,797 SO SOME OF THE CONCLUSIONS MVP 4338 04:19:12,797 --> 04:19:14,866 CAN HAVE SIGNIFICANT 4339 04:19:14,866 --> 04:19:16,301 ARRHYTHMOGENIC CONSEQUENCES. 4340 04:19:16,301 --> 04:19:19,070 I FEEL THERE'S PARALLELS BETWEEN 4341 04:19:19,070 --> 04:19:25,110 AVP AND ACM THAT CAN PROVIDE 4342 04:19:25,110 --> 04:19:32,250 RISK PROJECTION AND TRACK A 4343 04:19:32,250 --> 04:19:36,888 ARRHYTHMOGENIC RISK AND STRATEGY 4344 04:19:36,888 --> 04:19:38,990 A POSSIBILITY AND BY LOOKING 4345 04:19:38,990 --> 04:19:40,758 THROUGH THE ACM LENS WE CAN 4346 04:19:40,758 --> 04:19:42,293 BRIDGE THE GAP BETWEEN MECHANISM 4347 04:19:42,293 --> 04:19:44,329 AND THERAPEUTIC INTERVENTIONS. 4348 04:19:44,329 --> 04:19:48,766 COULD THERAPEUTICS FOR ACM BE 4349 04:19:48,766 --> 04:19:49,868 RELEVANT FOR MVP? 4350 04:19:49,868 --> 04:19:53,538 THEY SEEM TO HINGE ONLY SOME OF 4351 04:19:53,538 --> 04:19:56,441 THE SAME PATHWAYS. 4352 04:19:56,441 --> 04:20:03,014 EMERGING TECHNOLOGIES WILL BE 4353 04:20:03,014 --> 04:20:09,587 IMPORTANT FOR GENE LEARNING AND 4354 04:20:09,587 --> 04:20:11,322 EDITING TOOLS AND THE WORKSHOP 4355 04:20:11,322 --> 04:20:16,027 IS TO ENHANCE LONG-TERM OUTCOMES 4356 04:20:16,027 --> 04:20:18,530 IN THE VULNERABLE POPULATIONS 4357 04:20:18,530 --> 04:20:19,430 AND REDUCE SUDDEN DEATH RISK. 4358 04:20:19,430 --> 04:20:24,969 WITH THAT I WANT TO ACKNOWLEDGE 4359 04:20:24,969 --> 04:20:28,640 THE GROUP. 4360 04:20:28,640 --> 04:20:37,849 IT INVOLVES ACADEMIA AND 4361 04:20:37,849 --> 04:20:38,449 INDUSTRY. 4362 04:20:38,449 --> 04:20:38,850 THANK YOU. 4363 04:20:38,850 --> 04:20:41,519 >> THANK YOU. 4364 04:20:41,519 --> 04:20:44,989 VERY INTRIGUING. 4365 04:20:44,989 --> 04:20:47,058 DOES ANYONE HAVE A QUICK 4366 04:20:47,058 --> 04:20:47,759 QUESTION OR COMMENT ON THIS 4367 04:20:47,759 --> 04:20:58,169 PARTICULAR PRESENTATION? 4368 04:21:03,241 --> 04:21:04,909 AGAIN, THANK YOU VERY MUCH AND 4369 04:21:04,909 --> 04:21:06,144 WE'LL MOVE ON TO OUR FINAL 4370 04:21:06,144 --> 04:21:08,846 PRESENTATION FOR THE DAY. 4371 04:21:08,846 --> 04:21:13,551 FROM BENJAMIN HORNE. 4372 04:21:13,551 --> 04:21:15,119 >> THANK YOU. 4373 04:21:15,119 --> 04:21:17,522 HAVE YOU FOR THE OPPORTUNITY TO 4374 04:21:17,522 --> 04:21:19,357 PRESENT AT THE WORKSHOP. 4375 04:21:19,357 --> 04:21:23,528 I MENTIONED THE MULTIPLE P.I.s 4376 04:21:23,528 --> 04:21:29,534 FOR RECENTLY FUNDED GRANT ARM 4377 04:21:29,534 --> 04:21:33,004 RISK ASSESSMENT IN MITRAL VALVE 4378 04:21:33,004 --> 04:21:43,514 PROLAPSE AND MY CO-P.I. IS A 4379 04:21:44,249 --> 04:21:44,949 CARDIOLO 4380 04:21:44,949 --> 04:21:45,283 CARDIOLOGIST. 4381 04:21:45,283 --> 04:21:53,825 HERE ARE MY DISCLOSURES. 4382 04:21:53,825 --> 04:21:57,528 SO OUR PROJECT THE PROJECT WE'RE 4383 04:21:57,528 --> 04:22:02,934 PROPOSING ENGAGED IN NOW IS 4384 04:22:02,934 --> 04:22:04,602 SOLIDLY FOCUSSED ON RESEARCH 4385 04:22:04,602 --> 04:22:05,336 PRIORITY 2. 4386 04:22:05,336 --> 04:22:07,905 YOU MAY RECOGNIZE THIS FROM THE 4387 04:22:07,905 --> 04:22:11,509 WORKSHOP THREE YEARS AGO AND 4388 04:22:11,509 --> 04:22:14,112 WE'LL BE FOCUSSED ON RISK 4389 04:22:14,112 --> 04:22:15,113 ASSESSMENT OF MITRAL VALVE 4390 04:22:15,113 --> 04:22:17,515 PROLAPSE IN A LARGE 4391 04:22:17,515 --> 04:22:21,853 RETROSPECTIVE COHORT. 4392 04:22:21,853 --> 04:22:27,025 I GOT INTO THIS IN TWO 4393 04:22:27,025 --> 04:22:28,660 DIRECTIONS. 4394 04:22:28,660 --> 04:22:30,928 MY TRAINING IS IN GENETIC 4395 04:22:30,928 --> 04:22:34,198 EPIDEMIOLOGY I DID A STUDY USING 4396 04:22:34,198 --> 04:22:39,270 THE UTAH POPULATION DATABASE 4397 04:22:39,270 --> 04:22:43,941 LOOKING AT MITRAL VALVE DISEASE 4398 04:22:43,941 --> 04:22:48,980 AND AORTIC VALVE DISEASE AND DID 4399 04:22:48,980 --> 04:22:59,524 A SERIOUS STUDY AND DID CLINICAL 4400 04:23:10,835 --> 04:23:15,606 RISK MARKERS ON THE ELECTRONIC 4401 04:23:15,606 --> 04:23:17,642 HEALTH RECORD AND RECOGNIZED AS 4402 04:23:17,642 --> 04:23:21,546 THE FIRST ELECTRONIC HEALTH 4403 04:23:21,546 --> 04:23:31,823 RECORD IN 1960. 4404 04:23:42,734 --> 04:23:45,536 IT'S TO PARTICIPATE IN THE GROUP 4405 04:23:45,536 --> 04:23:55,646 TODAY. 4406 04:24:01,152 --> 04:24:05,390 AND THEY'RE SUPPORTED BY THE 4407 04:24:05,390 --> 04:24:11,529 EASE OF ANALYSIS AND ALSO THE 4408 04:24:11,529 --> 04:24:15,533 RELATIVELY WIDESPREAD DATABASE 4409 04:24:15,533 --> 04:24:17,602 THAT NOT ONLY IS RESEARCH DRIVEN 4410 04:24:17,602 --> 04:24:20,037 DATABASES BUT MOST INSTITUTIONS 4411 04:24:20,037 --> 04:24:23,141 IN THE U.S. ELECTRONIC HEALTH 4412 04:24:23,141 --> 04:24:23,608 RECORD. 4413 04:24:23,608 --> 04:24:25,843 UNFORTUNATELY THOUGH MANY OF THE 4414 04:24:25,843 --> 04:24:27,879 RISK PREDICTION TOOLS OR RISK 4415 04:24:27,879 --> 04:24:32,049 MODELS CREATED OFTEN USED 4416 04:24:32,049 --> 04:24:34,285 EXPENSIVE OR DIFFICULT TO OBTAIN 4417 04:24:34,285 --> 04:24:44,796 ELEMENTS FOR RISK PREDICTION. 4418 04:24:45,663 --> 04:24:55,940 AND ESOTERIC SCORES. 4419 04:24:56,574 --> 04:25:01,512 AND SOME ARE EASILY AVAILABLE 4420 04:25:01,512 --> 04:25:04,148 AND USED IN PRACTICE AND 4421 04:25:04,148 --> 04:25:07,485 INTEGRATED INTO ETHIC FOR 4422 04:25:07,485 --> 04:25:09,620 INSTITUTIONS THAT HAVE 4423 04:25:09,620 --> 04:25:10,221 ELECTRONIC HEALTH RECORDS. 4424 04:25:10,221 --> 04:25:12,156 SO THEY'RE EASILY AVAILABLE BUT 4425 04:25:12,156 --> 04:25:14,492 NOT PARTICULARLY GOOD AT 4426 04:25:14,492 --> 04:25:15,893 PREDICTING PATIENT OUTCOMES. 4427 04:25:15,893 --> 04:25:19,931 A KEY ISSUE WITH RISK PREDICTION 4428 04:25:19,931 --> 04:25:23,167 IS ENVIRONMENT AND PREDICTIVE 4429 04:25:23,167 --> 04:25:25,536 ABILITY OF A RISK PREDICTION 4430 04:25:25,536 --> 04:25:29,540 TOOL AND THE USABILITY OF RISK 4431 04:25:29,540 --> 04:25:31,709 PREDICTION TOOL WHICH ARE OFTEN 4432 04:25:31,709 --> 04:25:34,178 COMPETING GOALS BECAUSE MAKING 4433 04:25:34,178 --> 04:25:37,315 IT USABLE OFTEN MEANS NOT HAVING 4434 04:25:37,315 --> 04:25:39,450 HIGH THROUGHPUT PREDICTABILITY. 4435 04:25:39,450 --> 04:25:42,153 AND FEASIBILITY OF USING RISK 4436 04:25:42,153 --> 04:25:45,523 SCORE FOR PRACTICE IS OFTEN 4437 04:25:45,523 --> 04:25:48,059 CHALLENGING BECAUSE MOST RISK 4438 04:25:48,059 --> 04:25:50,094 SCORES REQUIRE YOU AS A 4439 04:25:50,094 --> 04:25:51,762 CLINICIAN TO FIND THE DATA 4440 04:25:51,762 --> 04:25:53,331 ELEMENTS, PUT IT INTO A 4441 04:25:53,331 --> 04:25:54,632 CALCULATOR AND CALCULATE THE 4442 04:25:54,632 --> 04:26:00,371 SCORE AND THEN KNOW HOW TO USE 4443 04:26:00,371 --> 04:26:10,882 IT AND IT CAN ADD TO THE RISK. 4444 04:26:14,285 --> 04:26:15,486 WE HAVE RISK PREDICTION TOOLS 4445 04:26:15,486 --> 04:26:19,924 AND FOCUS ON THE PARADIGM OF 4446 04:26:19,924 --> 04:26:25,096 USING COMMON STANDARDIZED 4447 04:26:25,096 --> 04:26:32,270 ALBEITRIES AND 4448 04:26:35,106 --> 04:26:37,308 AND THE METABOLIC PROFILE AT THE 4449 04:26:37,308 --> 04:26:39,443 BASE OR COMPREHENSIVE FINAL. 4450 04:26:39,443 --> 04:26:43,748 AND DEPENDING ON THE PRACTICE 4451 04:26:43,748 --> 04:26:44,282 SETTING OF THE PATIENT 4452 04:26:44,282 --> 04:26:47,518 POPULATION WE'LL ADD OTHER 4453 04:26:47,518 --> 04:26:48,953 FACTORS IN FOR EXAMPLE SIMPLE 4454 04:26:48,953 --> 04:26:54,992 CASE OF HEART FAILURE IN 4455 04:26:54,992 --> 04:26:55,259 PATIENTS. 4456 04:26:55,259 --> 04:26:59,297 WE PREDICT AND CAN DERIVE SCORES 4457 04:26:59,297 --> 04:27:02,833 AS WE DO FOR A VARIETY OF END 4458 04:27:02,833 --> 04:27:08,406 POINTS OF MORTALITY AND MAJOR 4459 04:27:08,406 --> 04:27:09,674 ADVERSE HEALTH. 4460 04:27:09,674 --> 04:27:11,475 AND DIAGNOSE VARIOUS TYPE OF 4461 04:27:11,475 --> 04:27:12,343 HEALTH CARE UTILIZATION. 4462 04:27:12,343 --> 04:27:17,515 THE FOCUS OF THIS APPROACH IS 4463 04:27:17,515 --> 04:27:24,889 THEY ARE EASILY CODABLE. 4464 04:27:24,889 --> 04:27:27,258 FOR EXAMPLE WE CREATED AND 4465 04:27:27,258 --> 04:27:29,627 PUBLISHED IN 2009 THE MORTALITY 4466 04:27:29,627 --> 04:27:33,297 RISK SCORE AND THIS IS A STRANGE 4467 04:27:33,297 --> 04:27:37,768 ONE FROM OUR ELECTRONIC HEALTH 4468 04:27:37,768 --> 04:27:42,273 RECORD AND HEALTH RECORD AND YOU 4469 04:27:42,273 --> 04:27:45,509 CAN SEE ON THE SCREEN FOR THE 4470 04:27:45,509 --> 04:27:47,845 METABOLIC FILE THERE'S RAY RISK 4471 04:27:47,845 --> 04:27:53,351 SCORE BUT IT DOESN'T COST 4472 04:27:53,351 --> 04:28:01,092 ANYTHING TO ORDER THAT AND USE 4473 04:28:01,092 --> 04:28:05,529 LABS USED IN THE LAST 24 HOURS 4474 04:28:05,529 --> 04:28:08,199 OF THE CLINICAL LAB MACHINES AND 4475 04:28:08,199 --> 04:28:13,804 RATES THE SCORING SO IF THERE IS 4476 04:28:13,804 --> 04:28:22,413 NO SCORING IN THE LAST 24 HOURS 4477 04:28:22,413 --> 04:28:24,915 IT'S USED BY A SKILLED PHYSICIAN 4478 04:28:24,915 --> 04:28:26,951 AND ALLIED HEALTH PROVIDERS. 4479 04:28:26,951 --> 04:28:29,520 AT THIS POINT WE DON'T SURFACE 4480 04:28:29,520 --> 04:28:34,625 THOUGH THERE IS ONE PROGRAM TO 4481 04:28:34,625 --> 04:28:43,701 RECALCULATE FOR IN PATIENTS. 4482 04:28:43,701 --> 04:28:49,507 IN 2014 WE DID START AN 4483 04:28:49,507 --> 04:28:51,876 IMPLEMENTATION OF RISK 4484 04:28:51,876 --> 04:28:53,678 PREDICTION TOOLS IN IN-PATIENT 4485 04:28:53,678 --> 04:28:56,981 HEART FAILURE AND THIS A SCREEN 4486 04:28:56,981 --> 04:28:58,249 SHOT OF THE DASHBOARD WE CREATED 4487 04:28:58,249 --> 04:28:59,350 FOR THE SUBJECT. 4488 04:28:59,350 --> 04:29:04,789 THIS IS PRIOR TO IMPLEMENTATION 4489 04:29:04,789 --> 04:29:09,460 OF THE E.H.R. 4490 04:29:09,460 --> 04:29:19,904 YOU CAN SEE ON THE RIGHT SIDE WE 4491 04:29:19,904 --> 04:29:22,673 DON'T PROVIDE THE RISK VALUE 4492 04:29:22,673 --> 04:29:28,312 JUST RED, YELLOW OR GENE 4493 04:29:28,312 --> 04:29:30,047 INDICATING SOMETHING ACTIONABLE 4494 04:29:30,047 --> 04:29:33,517 OR NOT AND INDIVIDUALS HAD TO 4495 04:29:33,517 --> 04:29:39,824 HAVE A RED TO TWO INTO HIGHER 4496 04:29:39,824 --> 04:29:40,091 INTENSITY. 4497 04:29:40,091 --> 04:29:45,529 THE RISK SCORE ON THE LEFT IS 4498 04:29:45,529 --> 04:29:49,033 THE PROBABILITY AT THE END OF 4499 04:29:49,033 --> 04:29:51,635 THE CURRENT SESSION WAS THE 4500 04:29:51,635 --> 04:29:53,337 LIKELIHOOD THE PRIMARY 4501 04:29:53,337 --> 04:29:54,371 DIAGNOSIS, DISCHARGE DIAGNOSIS 4502 04:29:54,371 --> 04:29:55,339 WILL BE HEART FAILURE. 4503 04:29:55,339 --> 04:30:02,680 THE MIDDLE ONE IS WILL 30-DAY 4504 04:30:02,680 --> 04:30:03,013 RE 4505 04:30:03,013 --> 04:30:04,949 RE-ADMISSION RISK AND ON THE 4506 04:30:04,949 --> 04:30:09,320 RIGHT THE 30 DAY. 4507 04:30:09,320 --> 04:30:12,790 THIS SLIDE PROVIDES A REVIEW OF 4508 04:30:12,790 --> 04:30:15,693 THE PROCESS WE DERIVED FOR THE 4509 04:30:15,693 --> 04:30:17,862 IN PATIENT HEART FAILURE 4510 04:30:17,862 --> 04:30:22,233 POPULATION WHERE THE CRITICAL 4511 04:30:22,233 --> 04:30:23,033 DECISION POINT IN THE CARE 4512 04:30:23,033 --> 04:30:25,536 PROCESS IS REPRESENTED TO THE 4513 04:30:25,536 --> 04:30:27,538 CENTER RIGHT WHERE THE TWO RISK 4514 04:30:27,538 --> 04:30:30,541 SCORES THE 30 DAY MORTALITY AND 4515 04:30:30,541 --> 04:30:32,877 OTHER SCORES WERE CRITICAL IN 4516 04:30:32,877 --> 04:30:34,411 DECIDING IS THE PATIENT GO INTO 4517 04:30:34,411 --> 04:30:37,515 THE HIGHER INTENSITY CARE 4518 04:30:37,515 --> 04:30:41,452 PROCESS OR ALL HANDS ON DECK ALL 4519 04:30:41,452 --> 04:30:43,320 PARTICIPANTS IN 4520 04:30:43,320 --> 04:30:48,626 MULTIDISCIPLINARY TEAM HAVE 4521 04:30:48,626 --> 04:30:52,596 SPECIFIC WRITTEN THINGS THEY 4522 04:30:52,596 --> 04:30:54,532 HAVE TO DO FOR EVALUATING AND 4523 04:30:54,532 --> 04:31:05,009 TREATING HIGH RISK PATIENTS. 4524 04:31:06,710 --> 04:31:11,549 FOR THOSE WITH LOW OR MODERATE 4525 04:31:11,549 --> 04:31:15,319 RISK WENT TO STANDARD CARE ARM 4526 04:31:15,319 --> 04:31:16,954 WHERE THEY RECEIVED A STANDARD 4527 04:31:16,954 --> 04:31:22,293 PACKAGE OF CARE AND ENDED UP 4528 04:31:22,293 --> 04:31:22,893 RECEIVING LESS ATTENTION AND 4529 04:31:22,893 --> 04:31:31,335 LESS TIME. 4530 04:31:31,335 --> 04:31:38,375 IN THE END THE AND WOULD LIKE 30 4531 04:31:38,375 --> 04:31:42,613 DAY READMISSION AND MORTALITY IN 4532 04:31:42,613 --> 04:31:47,551 A STEP WEDGE IMPLEMENTATION 4533 04:31:47,551 --> 04:31:54,124 ACROSS 22 HOSPITALS. 4534 04:31:54,124 --> 04:31:58,329 MORTALITY AND PATIENTS WE SAW 4535 04:31:58,329 --> 04:32:03,500 REGRESSION IN RISK BEFORE 4536 04:32:03,500 --> 04:32:08,038 IMPLEMENTATION OF THE PROCESS 4537 04:32:08,038 --> 04:32:09,240 FOR INDIVIDUALS WITH LOWER RISK 4538 04:32:09,240 --> 04:32:13,510 OR MODERATE CHANGE THERE WAS NO 4539 04:32:13,510 --> 04:32:23,787 CHANGE OF RISK. 4540 04:32:27,424 --> 04:32:28,225 GOING FORWARD THERE MAY BE 4541 04:32:28,225 --> 04:32:31,061 SOMETHING ON THE SLIDE I FORGOT 4542 04:32:31,061 --> 04:32:31,929 TO TAKE OFF. 4543 04:32:31,929 --> 04:32:32,329 THANK YOU. 4544 04:32:32,329 --> 04:32:36,934 HOW DO WE TRANSLATE THIS 4545 04:32:36,934 --> 04:32:37,968 CLINICAL RISK PREDICTION PROCESS 4546 04:32:37,968 --> 04:32:42,606 WE'VE CREATED OVER THE LAST 20 4547 04:32:42,606 --> 04:32:44,742 YEARS INTO MITRAL VALVE 4548 04:32:44,742 --> 04:32:48,712 PROLAPSE? 4549 04:32:48,712 --> 04:32:53,183 WHAT WE ENVISION IS IT CAN 4550 04:32:53,183 --> 04:32:54,618 ADDRESS UNDER DIAGNOSIS AND LATE 4551 04:32:54,618 --> 04:32:57,521 REFERRAL AND TREATMENT BECAUSE 4552 04:32:57,521 --> 04:33:00,891 IT WILL STANDARDIZE THE 4553 04:33:00,891 --> 04:33:10,534 ASSESSMENT OF RISK AND RIGHT 4554 04:33:10,534 --> 04:33:13,537 CARE AT THE RIGHT TIME AT THE 4555 04:33:13,537 --> 04:33:16,807 RIGHT PLACE TO ALL INDIVIDUALS 4556 04:33:16,807 --> 04:33:20,611 REGARDLESS OF SOCIO DEMOGRAPHICS 4557 04:33:20,611 --> 04:33:26,517 AND THIS IS BASED ON POPULATION 4558 04:33:26,517 --> 04:33:29,520 EVALUATIONS AND INVOLVES 4559 04:33:29,520 --> 04:33:30,988 PERSONALIZED MEDICINE TO BE USED 4560 04:33:30,988 --> 04:33:34,458 IN CLINIC AND PRIMARY AND 4561 04:33:34,458 --> 04:33:37,094 SECONDARY CLINICS AND HOSPITAL 4562 04:33:37,094 --> 04:33:40,364 BASED AND HELP DRIVE EDUCATION 4563 04:33:40,364 --> 04:33:41,832 FOR PHYSICIAN AND PATIENTS AND 4564 04:33:41,832 --> 04:33:52,276 THE STANDARDIZED APPROACH. 4565 04:33:53,510 --> 04:33:54,244 TRANSFORMING THE EARLY BIOMARKER 4566 04:33:54,244 --> 04:34:01,251 BASED APPROACH WE HAVE TO MODIFY 4567 04:34:01,251 --> 04:34:02,853 THAT FOR MITRAL VALVE MITRAL 4568 04:34:02,853 --> 04:34:04,188 VALVE INCLUDES USING THE 4569 04:34:04,188 --> 04:34:06,657 LABORATORY ACTORS WHICH ARE 4570 04:34:06,657 --> 04:34:12,096 COMMON ACROSS MEDICINE MORE THAN 4571 04:34:12,096 --> 04:34:22,773 95% OF PATIENTS IN ALL CARE SEC 4572 04:34:30,381 --> 04:34:32,116 SETTINGS SO THEY'RE UBIQUITOUS 4573 04:34:32,116 --> 04:34:33,617 AND AVAILABLE AND ADDING ON SOME 4574 04:34:33,617 --> 04:34:38,188 OF THE COMPONENTS THAT ARE 4575 04:34:38,188 --> 04:34:42,192 SPECIFIC TO THE DIAGNOSIS OF 4576 04:34:42,192 --> 04:34:42,860 MITRAL VALVE PROLAPSE AND THAT 4577 04:34:42,860 --> 04:34:48,866 INVOLVES IMAGING AND ECB AND 4578 04:34:48,866 --> 04:34:57,007 OTHER PARAMETERS AVAILABLE A 4579 04:34:57,007 --> 04:34:58,776 CAVEAT IS WE DON'T NEED RISK 4580 04:34:58,776 --> 04:35:04,081 PREDICTORS BECAUSE SOME OF THE 4581 04:35:04,081 --> 04:35:08,719 FACTO 4582 04:35:08,719 --> 04:35:15,426 FACTORS AND AT LEAST NOT ON A 4583 04:35:15,426 --> 04:35:18,695 FULL BODY FRAMEWORK CAPTURES THE 4584 04:35:18,695 --> 04:35:21,632 RISK VARIANTS AND THE STUDIES WE 4585 04:35:21,632 --> 04:35:27,337 PUBLISHED IN 2020 THE RISK SCORE 4586 04:35:27,337 --> 04:35:29,540 ON TO THE PANELS AND THE 4587 04:35:29,540 --> 04:35:30,941 MORTALITY RISK SCORE CAPTURED 4588 04:35:30,941 --> 04:35:36,947 63% OF THE VARIANTS FOR 4589 04:35:36,947 --> 04:35:40,050 IN-HOSPITAL MORTALITY AND IT CAN 4590 04:35:40,050 --> 04:35:45,055 DO VERY WELL WITHOUT TO PREDICT 4591 04:35:45,055 --> 04:35:46,056 OUTCOMES AND STILL SUBSTANTIAL 4592 04:35:46,056 --> 04:35:53,697 AT ONE YEAR AND FIVE-YEARS. 4593 04:35:53,697 --> 04:35:57,534 SO USING A RISK MODEL BY 4594 04:35:57,534 --> 04:36:00,737 DECREASING THE COSTS BOTH IN 4595 04:36:00,737 --> 04:36:02,206 TERMS OF FINANCIAL COST AND TIME 4596 04:36:02,206 --> 04:36:08,545 TO COLLECT DATA AND THE DATA 4597 04:36:08,545 --> 04:36:13,517 ACCURACY FOR WHERE THEY MAY NOT 4598 04:36:13,517 --> 04:36:16,186 HAVE RISK PREDICTOR AVAILABLE 4599 04:36:16,186 --> 04:36:18,856 AND PROLAPSE AND THERE ARE 4600 04:36:18,856 --> 04:36:23,460 ADDITIONAL FACTORS THAT AT THE 4601 04:36:23,460 --> 04:36:25,529 DIFFERENT STAGES OF DIAGNOSIS 4602 04:36:25,529 --> 04:36:27,231 DATA ELEMENTS BECOME AVAILABLE 4603 04:36:27,231 --> 04:36:29,766 SO INTEGRATE THOSE INTO RISK 4604 04:36:29,766 --> 04:36:35,572 PREDICTION TOOLS THAT ARE 4605 04:36:35,572 --> 04:36:45,516 RELEVANT TO THE DIFFERENT FORM 4606 04:36:45,516 --> 04:36:55,959 OF MITRAL VALVE PROLAPSE. 4607 04:37:04,635 --> 04:37:08,972 THIS IS TO CREATE THE RISK 4608 04:37:08,972 --> 04:37:11,308 SCORES AND USE FOR 4609 04:37:11,308 --> 04:37:14,778 IMPLEMENTATIONS WHERE IT WILL BE 4610 04:37:14,778 --> 04:37:16,380 USABLE AND AVAILABLE TO 4611 04:37:16,380 --> 04:37:18,715 CLINICIANS FOR PEOPLE AT RISK OF 4612 04:37:18,715 --> 04:37:22,119 POORER OUTCOMES AND GET MORE 4613 04:37:22,119 --> 04:37:24,254 PRECISE CARE FOR THE INDIVIDUALS 4614 04:37:24,254 --> 04:37:30,694 AT AN EARLIER TIME TO PREVENT 4615 04:37:30,694 --> 04:37:41,238 FURTHER DAMAGE TO THE HEART THIL 4616 04:37:43,640 --> 04:37:48,912 LOOKS AT PROLAPSE IN OUR 4617 04:37:48,912 --> 04:37:58,355 POPULATION. 4618 04:37:58,355 --> 04:38:01,358 AIM TWO IS THE REGISTRY WE 4619 04:38:01,358 --> 04:38:07,130 TALKED ABOUT EARLIER AND FOLLOW 4620 04:38:07,130 --> 04:38:12,736 POPULATIONS. 4621 04:38:12,736 --> 04:38:13,537 AND LOOKING TOWARDS 4622 04:38:13,537 --> 04:38:20,978 IMPLEMENTATION. 4623 04:38:20,978 --> 04:38:26,416 SO OUR DATA THAT WE HAVE 4624 04:38:26,416 --> 04:38:28,719 AVAILABLE WE ACTUALLY HAVE THE 4625 04:38:28,719 --> 04:38:33,223 DATA GOING BACK 30 YEARS OR SO 4626 04:38:33,223 --> 04:38:40,130 AND INCREASED TO 250 CLINICS AND 4627 04:38:40,130 --> 04:38:43,467 THAT INCLUDES A RECENTLY BUILT 4628 04:38:43,467 --> 04:38:48,605 CHILDREN'S HOSPITAL AND IN 2022 4629 04:38:48,605 --> 04:38:51,541 WE INTEGRATED ANOTHER SYSTEM 4630 04:38:51,541 --> 04:38:54,111 WITH NINE HOSPITALS AND HOW HAVE 4631 04:38:54,111 --> 04:38:58,615 33 HOSPITALS AND ABOUT 385 4632 04:38:58,615 --> 04:39:00,884 CLINICS ACROSS UTAH AND IDAHO 4633 04:39:00,884 --> 04:39:05,155 AND MONTANA, COLORADO, MANY 4634 04:39:05,155 --> 04:39:05,422 PATIENTS. 4635 04:39:05,422 --> 04:39:09,559 I'VE TRAVELED TO UTAH. 4636 04:39:09,559 --> 04:39:12,896 WE HAVE ELECTRONIC DATA FROM ECG 4637 04:39:12,896 --> 04:39:19,036 GOING BACK MORE THAN 30 YEARS 4638 04:39:19,036 --> 04:39:25,509 INDICATING VARIOUS MOSTLY 20 4639 04:39:25,509 --> 04:39:30,347 YEARS WORTH. 4640 04:39:30,347 --> 04:39:35,852 AIM TWO IS LOOKING AT RISK IN A 4641 04:39:35,852 --> 04:39:38,889 VARIETY OF WAYS. 4642 04:39:38,889 --> 04:39:46,630 THE HERITABLE RISK AND 4643 04:39:46,630 --> 04:39:49,566 FAMILIARITY OF GENETIC RISK FOR 4644 04:39:49,566 --> 04:39:51,802 DISEASE AND ELECTRONIC HEALTH 4645 04:39:51,802 --> 04:39:53,236 RECORD FOR MORE THAN 24 MILLION 4646 04:39:53,236 --> 04:39:59,142 PEOPLE IN PEDIGREE STRUCTURE IN 4647 04:39:59,142 --> 04:40:02,846 UTAH OR SURROUNDING STATE THAT 4648 04:40:02,846 --> 04:40:06,750 SHARES A BORDER AND MORE THAN 4649 04:40:06,750 --> 04:40:08,552 700,000 PATIENTS IN THE 4650 04:40:08,552 --> 04:40:10,454 ELECTRONIC HEALTH RECORD LINKED 4651 04:40:10,454 --> 04:40:17,527 TO THOSE CATEGORIES AND ABLE TO 4652 04:40:17,527 --> 04:40:21,965 EVALUATE DESPITE THE CLUSTERING 4653 04:40:21,965 --> 04:40:29,506 OF PROLAPSE AND ALSO BASED ON 4654 04:40:29,506 --> 04:40:30,574 SUBPHENOTYPES SUCH AS SEVERITY 4655 04:40:30,574 --> 04:40:32,943 AND DISEASE AND ARRHYTHMIAS AND 4656 04:40:32,943 --> 04:40:42,085 OTHER CHARACTERISTICS. 4657 04:40:42,085 --> 04:40:46,823 AND LOOKING AT GENETIC RISK FOR 4658 04:40:46,823 --> 04:40:49,159 205,000 INDIVIDUALS INVOLVED 4659 04:40:49,159 --> 04:40:54,030 SINCE 2018 AND ABOUT 70,000 WE 4660 04:40:54,030 --> 04:40:59,503 HAVE FULL SEQUENCING. 4661 04:40:59,503 --> 04:41:00,370 COLLABORATION OTHER THAN THAT 4662 04:41:00,370 --> 04:41:02,439 FROM PHARMACEUTICAL COMPANIES 4663 04:41:02,439 --> 04:41:05,542 ARE AVAILABLE TO US NOW. 4664 04:41:05,542 --> 04:41:09,579 THERE'S INTEREST IN MITRAL VALVE 4665 04:41:09,579 --> 04:41:19,756 PROLAPSE. 4666 04:41:23,293 --> 04:41:27,697 THESE ARE A COUPLE PEDIGREES 4667 04:41:27,697 --> 04:41:33,737 FROM A SMALL GRANT FROM A LOCAL 4668 04:41:33,737 --> 04:41:39,309 FOUNDATION AND EVALUATED 4669 04:41:39,309 --> 04:41:40,510 FAMILIARITY OF THE MITRAL VALVE 4670 04:41:40,510 --> 04:41:41,545 PROLAPSE AND FOUND PEDIGREES 4671 04:41:41,545 --> 04:41:45,482 WHAT WE WERE DOING IN THE 4672 04:41:45,482 --> 04:41:51,922 PROJECT WAS ENROLLED AND 4673 04:41:51,922 --> 04:41:56,326 PARTICIPATING IN AN 4674 04:41:56,326 --> 04:41:58,061 INTERNATIONAL STUDY MENTIONED 4675 04:41:58,061 --> 04:42:01,531 EARLIER AND PUBLISHED I BELIEVE 4676 04:42:01,531 --> 04:42:11,441 IN 2021. 4677 04:42:11,441 --> 04:42:20,817 THE HEREDIGENE STUDY LOOKING AT 4678 04:42:20,817 --> 04:42:26,122 A POPULATION LINKED TO THE 4679 04:42:26,122 --> 04:42:30,794 ELECTRONIC HEALTH RECORD AND THE 4680 04:42:30,794 --> 04:42:39,469 DATA IS AVAILABLE. 4681 04:42:39,469 --> 04:42:42,072 WE'LL FOCUS ON THE GENETIC 4682 04:42:42,072 --> 04:42:43,240 VARIANTS AND ADDING THOSE 4683 04:42:43,240 --> 04:42:46,142 GENETIC VARIANTS MOSTLY WILL 4684 04:42:46,142 --> 04:42:50,780 FOCUS ON VARIANTS PUBLISHED IN 4685 04:42:50,780 --> 04:42:52,849 THE LITERATURE AND PUBLISHED AND 4686 04:42:52,849 --> 04:42:57,521 THEN ADDING IN OTHER CLINICAL 4687 04:42:57,521 --> 04:43:05,829 FACTORS TO PREDICT. 4688 04:43:05,829 --> 04:43:10,200 FINALLY LOOKING AT THE RISK 4689 04:43:10,200 --> 04:43:12,202 PREDICTION TOOLS TO IDENTIFY 4690 04:43:12,202 --> 04:43:17,474 PATIENTS AND STRATIFY THEM BASED 4691 04:43:17,474 --> 04:43:23,113 ON THEIR RISK FOR VARIOUS STATES 4692 04:43:23,113 --> 04:43:25,348 AND TO POWER PERSONALIZED 4693 04:43:25,348 --> 04:43:26,283 TREATMENT HELPING THEM LIVE 4694 04:43:26,283 --> 04:43:32,389 LONGER. 4695 04:43:32,389 --> 04:43:38,028 RISK MODELLING WILL USE 4696 04:43:38,028 --> 04:43:39,296 TRADITIONAL STATISTICS. 4697 04:43:39,296 --> 04:43:41,164 VALIDATE THE RISK SCORES AT 4698 04:43:41,164 --> 04:43:51,608 VARIOUS SITES PARTICIPATING. 4699 04:43:51,608 --> 04:43:52,909 THAT'S IT AND THANK YOU. 4700 04:43:52,909 --> 04:43:53,577 THANK YOU BEEN FOR YOUR TIME AND 4701 04:43:53,577 --> 04:43:57,581 ATTENTION. 4702 04:43:57,581 --> 04:43:59,115 >> THANK YOU VERY MUCH. 4703 04:43:59,115 --> 04:44:00,183 DOES ANYONE HAVE COMMENTS OR 4704 04:44:00,183 --> 04:44:09,225 QUESTIONS ON THIS PRESENTATION? 4705 04:44:09,225 --> 04:44:13,830 >> I HAD A HARD TIME HEARING 4706 04:44:13,830 --> 04:44:15,131 EVERYTHING SO ARE THERE -- ARE 4707 04:44:15,131 --> 04:44:23,940 YOU AWARE OF EXISTING SCORE 4708 04:44:23,940 --> 04:44:24,541 SYSTEM FOR MVP? 4709 04:44:24,541 --> 04:44:28,411 >> FROM WHAT I READ THERE'S NO 4710 04:44:28,411 --> 04:44:33,316 SCORE SYSTEMS USED FOR THE 4711 04:44:33,316 --> 04:44:34,484 MITRAL VALVE PROLAPSE. 4712 04:44:34,484 --> 04:44:45,061 CERTAINLY RISK MODELS AND 4713 04:44:48,565 --> 04:44:52,302 THERE'S GWAS AND THAT WOULD BE 4714 04:44:52,302 --> 04:44:55,605 SOMETHING THAT APPLIES DIRECTLY 4715 04:44:55,605 --> 04:44:58,008 TO THAT THAT EXIST AND ARE AWARE 4716 04:44:58,008 --> 04:45:00,510 OF THE SCORE THAT APPLIES TO MVP 4717 04:45:00,510 --> 04:45:10,020 AND A SCORE THAT ALLOWS 4718 04:45:10,020 --> 04:45:11,187 SURVIVAL -- 4719 04:45:11,187 --> 04:45:19,062 >> NIDA. 4720 04:45:19,062 --> 04:45:23,566 >> ONE PUBLISHED IN EUROPEAN 4721 04:45:23,566 --> 04:45:29,506 HEART JOURNAL AND ONE IN 4722 04:45:29,506 --> 04:45:30,006 CIRCULATION. 4723 04:45:30,006 --> 04:45:33,510 I DON'T KNOW HOW YOU INTEGRATE 4724 04:45:33,510 --> 04:45:34,477 THAT IN YOUR. 4725 04:45:34,477 --> 04:45:35,345 -- AIMS. 4726 04:45:35,345 --> 04:45:37,147 >> THOSE ARE THINGS TO EVALUATE 4727 04:45:37,147 --> 04:45:41,518 AND LOOK AT THE COMPONENTS OF 4728 04:45:41,518 --> 04:45:46,189 THE SCORES. 4729 04:45:46,189 --> 04:45:53,530 >> ARE YOU LOOKING ALSO AT 4730 04:45:53,530 --> 04:45:55,131 ARRHYTHMOGENIC RISK OR MOST 4731 04:45:55,131 --> 04:45:58,268 HEART FALL FAILURE. 4732 04:45:58,268 --> 04:46:00,970 THE ARRHYTHMOGENIC RISK COULD 4733 04:46:00,970 --> 04:46:05,108 POTENTIALLY BE OF GREAT VALUE TO 4734 04:46:05,108 --> 04:46:08,111 PARTNER WITH PEOPLE LIKE 4735 04:46:08,111 --> 04:46:09,579 FRANCESCA DELLINGS AND OTHERS TO 4736 04:46:09,579 --> 04:46:11,548 GIVE A MORE DETAILED PHENOTYPE 4737 04:46:11,548 --> 04:46:15,952 AND BELIEVE THE PATIENTS LARGELY 4738 04:46:15,952 --> 04:46:18,722 HAVE ECHOCARDIOGRAMS AND CAN 4739 04:46:18,722 --> 04:46:20,623 IMMENSELY HELP YOUR PREDICTIVE 4740 04:46:20,623 --> 04:46:21,157 VALUE? 4741 04:46:21,157 --> 04:46:28,465 >> WE'LL LOOK AT HEART FAILURE 4742 04:46:28,465 --> 04:46:38,875 AND ARRHYTHMIC AND HAVE 4743 04:46:40,176 --> 04:46:43,012 ECHOCARDIOGRAMS WITH A LONG 4744 04:46:43,012 --> 04:46:53,490 HISTORY AND ELECTRONIC DATA. 4745 04:46:58,428 --> 04:46:59,262 >> VERY INTERESTING. 4746 04:46:59,262 --> 04:47:02,365 MAYBE YOU MENTIONED THIS, HOW DO 4747 04:47:02,365 --> 04:47:03,833 YOU CAPTURE THE ARRHYTHMIC 4748 04:47:03,833 --> 04:47:06,369 INFORMATION FROM THE MEDICAL 4749 04:47:06,369 --> 04:47:06,603 RECORDS? 4750 04:47:06,603 --> 04:47:09,572 A LOT OF THIS IS IN MONITOR 4751 04:47:09,572 --> 04:47:12,308 RECORD OR TELEMETRY ARE YOU 4752 04:47:12,308 --> 04:47:17,247 USING NATURAL LANGUAGE 4753 04:47:17,247 --> 04:47:20,416 PROCESSING OR REVERSE CODES OR 4754 04:47:20,416 --> 04:47:22,218 HOW ARE YOU TESTING THAT? 4755 04:47:22,218 --> 04:47:26,689 >> ULTRA MONITORING RESULTS AND 4756 04:47:26,689 --> 04:47:33,530 ECT DATA ARE AVAILABLE IN THE 4757 04:47:33,530 --> 04:47:39,402 ELECTRONIC FORMATS AND HAVE SOME 4758 04:47:39,402 --> 04:47:44,908 STRUCTURES THAT THEN WE HAVE 4759 04:47:44,908 --> 04:47:53,750 THOSE GOING BACK TO 1993. 4760 04:47:53,750 --> 04:47:57,120 I DON'T KNOW ABOUT INTENSIVE 4761 04:47:57,120 --> 04:47:58,988 CARE UNITS. 4762 04:47:58,988 --> 04:48:08,164 >> SO FOR THE AMBULATORY EKG ARE 4763 04:48:08,164 --> 04:48:10,433 YOU LOOKING AT REPORTS OR THE 4764 04:48:10,433 --> 04:48:12,468 SCRIPTS OF THE AMBULATORY 4765 04:48:12,468 --> 04:48:13,469 MONITORING? 4766 04:48:13,469 --> 04:48:19,175 >> WE LOOK TO THE STRUCTURED 4767 04:48:19,175 --> 04:48:23,580 DATA BUT THE OTHER DATA THE ECG 4768 04:48:23,580 --> 04:48:25,048 REPORTING IS AVAILABLE. 4769 04:48:25,048 --> 04:48:28,852 THAT'S ONE GOAL IN THE PROJECT. 4770 04:48:28,852 --> 04:48:32,322 WE'RE NOT EXPERTS AT USING 4771 04:48:32,322 --> 04:48:33,790 MACHINE LEARNING. 4772 04:48:33,790 --> 04:48:42,298 BUT WE HAVE PROCESSING. 4773 04:48:42,298 --> 04:48:45,501 I HAVEN'T DONE THAT PERSONALLY. 4774 04:48:45,501 --> 04:48:48,471 IT'S SOMETHING WE HAVE AVAILABLE 4775 04:48:48,471 --> 04:48:48,605 . 4776 04:48:48,605 --> 04:48:51,941 IF YOU HAVE SOME INSIGHTS I'D 4777 04:48:51,941 --> 04:48:53,776 LOVE TO TALK. 4778 04:48:53,776 --> 04:48:56,646 >> I DON'T KNOW ANY OTHER WAY 4779 04:48:56,646 --> 04:48:57,780 OTHER THAN NATURAL LANGUAGE 4780 04:48:57,780 --> 04:48:59,616 PROCESSING TO GET THROUGH THE 4781 04:48:59,616 --> 04:48:59,849 REPORTS. 4782 04:48:59,849 --> 04:49:02,352 THAT'S WHY I'M ASKING. 4783 04:49:02,352 --> 04:49:04,254 >> WE HAVEN'T JUMPED INTO THAT 4784 04:49:04,254 --> 04:49:04,487 YET. 4785 04:49:04,487 --> 04:49:05,521 WE DO HAVE EXPERTS IN THAT 4786 04:49:05,521 --> 04:49:12,095 PROCESS. 4787 04:49:12,095 --> 04:49:17,967 I'VE NOT YET USED ECG DATA IN 4788 04:49:17,967 --> 04:49:19,502 THAT WAY. 4789 04:49:19,502 --> 04:49:23,940 >> THANK YOU. 4790 04:49:23,940 --> 04:49:24,974 >> YEAH. 4791 04:49:24,974 --> 04:49:26,175 >> OKAY, THANK YOU VERY MUCH. 4792 04:49:26,175 --> 04:49:31,614 BEFORE WE GO, I'D LIKE TO TAKE 4793 04:49:31,614 --> 04:49:33,149 THE ORGANIZER'S PREROGATIVE AND 4794 04:49:33,149 --> 04:49:43,693 SHARE A COUPLE SLIDES WITH YOU. 4795 04:49:46,195 --> 04:49:47,530 SO AFTER WE ESTABLISHED THE 4796 04:49:47,530 --> 04:49:49,532 AGENDA AND THE ROSTER, I 4797 04:49:49,532 --> 04:49:57,807 HAPPENED TO HEAR A TALK FROM 4798 04:49:57,807 --> 04:49:59,575 JOHNS HOPKINS ON THE USE OF 4799 04:49:59,575 --> 04:50:04,013 DIGITAL TWINS. 4800 04:50:04,013 --> 04:50:07,450 AND JUST TO MENTION, WHAT SHE'S 4801 04:50:07,450 --> 04:50:11,587 DOING IS LOOKING AT MRI IMAGES 4802 04:50:11,587 --> 04:50:17,160 OF THE HEART TOGETHER WITH 4803 04:50:17,160 --> 04:50:20,330 ESTIMATES OF FIBROSIS AND THEN 4804 04:50:20,330 --> 04:50:23,466 INCORPORATING MEMBRANE MODELS 4805 04:50:23,466 --> 04:50:26,235 WHICH MAY INCORPORATE 4806 04:50:26,235 --> 04:50:28,471 CHANNELOPATHIES AND ESTIMATING 4807 04:50:28,471 --> 04:50:30,306 FROM VARIOUS STIMULUS PATTERNS 4808 04:50:30,306 --> 04:50:37,347 WHETHER OR NOT SHE CAN INDUCE 4809 04:50:37,347 --> 04:50:38,381 ARRHYTHMIAS WHICH SEEMED LIKE AN 4810 04:50:38,381 --> 04:50:39,082 INTERESTING APPROACH. 4811 04:50:39,082 --> 04:50:40,316 I WANTED TO BRING IT TO THE 4812 04:50:40,316 --> 04:50:48,124 ATTENTION OF THIS GROUP. 4813 04:50:48,124 --> 04:50:50,693 SHE'S REPORTED SOME IMPRESSIVE 4814 04:50:50,693 --> 04:50:53,529 RESULTS IN A VARIETY OF 4815 04:50:53,529 --> 04:50:57,533 CONDITIONS BUT NOT AS IT IS IN 4816 04:50:57,533 --> 04:51:00,136 MITRAL VALVE PROLAPSE. 4817 04:51:00,136 --> 04:51:00,770 THAT'S IT. 4818 04:51:00,770 --> 04:51:01,604 I JUST WANTED TO MENTION THAT. 4819 04:51:01,604 --> 04:51:03,673 THANK YOU. 4820 04:51:03,673 --> 04:51:04,273 >> THANK YOU. 4821 04:51:04,273 --> 04:51:07,910 I HAVE A COMMENT ABOUT THAT, IF 4822 04:51:07,910 --> 04:51:08,945 I MAY. 4823 04:51:08,945 --> 04:51:12,982 I THINK SHE'S DONE A LOT OF WORK 4824 04:51:12,982 --> 04:51:20,156 ON SARCOID MYOPATHY USING A 4825 04:51:20,156 --> 04:51:23,726 VARIETY OF TOOLS INCLUDING 4826 04:51:23,726 --> 04:51:27,530 METHODS AND DON'T KNOW IF IT'S 4827 04:51:27,530 --> 04:51:29,532 TRANSLATED INTO ANYTHING 4828 04:51:29,532 --> 04:51:31,934 CLINICALLY HELPFUL. 4829 04:51:31,934 --> 04:51:35,571 SOMEONE ON THE CALL CAN COMMENT. 4830 04:51:35,571 --> 04:51:38,674 I KNOW THERE WAS SOME 4831 04:51:38,674 --> 04:51:39,776 SARCOIDOSIS USING A SIMILAR 4832 04:51:39,776 --> 04:51:44,814 APPROACH BY THE SAME GROUP. 4833 04:51:44,814 --> 04:51:49,852 >> THE PATIENTS ARE VOID OF 4834 04:51:49,852 --> 04:51:50,219 CHANNELOPATHIES. 4835 04:51:50,219 --> 04:51:52,021 >> YES, YES. 4836 04:51:52,021 --> 04:51:56,859 YOU ARE CORRECT. 4837 04:51:56,859 --> 04:51:59,862 MY QUESTION WAS MORE ABOUT THE 4838 04:51:59,862 --> 04:52:05,368 TRANSLATABILITY OF THE MODEL 4839 04:52:05,368 --> 04:52:06,135 INTO MITRAL VALVE PROLAPSE AND 4840 04:52:06,135 --> 04:52:09,205 WHETHER THE STUDY DONE IN 4841 04:52:09,205 --> 04:52:11,240 SARCOIDOSIS HAD ANY APPLICATION 4842 04:52:11,240 --> 04:52:14,010 CLINICALLY BECAUSE IT WAS USING 4843 04:52:14,010 --> 04:52:15,144 THE SAME MACHINE LEARNING TOOL 4844 04:52:15,144 --> 04:52:18,448 AND PREDICTION AND CARDIAC 4845 04:52:18,448 --> 04:52:18,714 RECORDING. 4846 04:52:18,714 --> 04:52:21,317 I DON'T KNOW IF 4847 04:52:21,317 --> 04:52:23,586 ELECTROPHYSIOLOGISTS ARE USING 4848 04:52:23,586 --> 04:52:25,121 THAT TO PREDICT RISK. 4849 04:52:25,121 --> 04:52:29,525 >> ABOUT WHAT IS DIGITAL TWIN 4850 04:52:29,525 --> 04:52:30,159 MEAN? 4851 04:52:30,159 --> 04:52:33,529 >> CREATING A DIGITAL MODEL A 4852 04:52:33,529 --> 04:52:42,772 PART. 4853 04:52:42,772 --> 04:52:44,874 IT'S A VERY DETAILED SIMULATION. 4854 04:52:44,874 --> 04:52:45,908 >> OH, IT'S A SIMULATION. 4855 04:52:45,908 --> 04:52:48,711 OKAY. 4856 04:52:48,711 --> 04:52:51,013 >> I THINK WE FOUND SOMETHING WE 4857 04:52:51,013 --> 04:52:53,583 HAVEN'T SEEN BEFORE WITH THE 4858 04:52:53,583 --> 04:52:56,619 MODEL ON THE LEFT VENTRICLE AND 4859 04:52:56,619 --> 04:52:57,420 REGARDLESS OF SEVERITY. 4860 04:52:57,420 --> 04:53:05,394 IT'S A GREAT IDEA. 4861 04:53:05,394 --> 04:53:08,030 >> I'M ANOTHER ADVOCATING OR 4862 04:53:08,030 --> 04:53:09,532 OTHER WISE BUT SOUNDED 4863 04:53:09,532 --> 04:53:10,299 INTRIGUING AND WANTED TO BRING 4864 04:53:10,299 --> 04:53:11,734 IT TO THE ATTENTION OF THE 4865 04:53:11,734 --> 04:53:11,934 GROUP. 4866 04:53:11,934 --> 04:53:14,403 I WANT TO THANK EVERYBODY FOR 4867 04:53:14,403 --> 04:53:16,973 YOUR PARTICIPATION TODAY. 4868 04:53:16,973 --> 04:53:18,774 THIS HAS BEEN I THINK AN 4869 04:53:18,774 --> 04:53:19,642 EXCELLENT FIRST DAY. 4870 04:53:19,642 --> 04:53:25,615 GREAT DISCUSSION. 4871 04:53:25,615 --> 04:53:27,850 WE WERE KIND OF IN CLINICAL AND 4872 04:53:27,850 --> 04:53:29,552 BASIC AND CLINICAL AGAIN AND 4873 04:53:29,552 --> 04:53:33,523 WE'RE GOING TO TO THAT SAME 4874 04:53:33,523 --> 04:53:36,659 PATTERN TOMORROW. 4875 04:53:36,659 --> 04:53:37,527 DOES ANYONE HAVE ANY FINAL 4876 04:53:37,527 --> 04:53:41,330 COMMENTS OR QUESTIONS? 4877 04:53:41,330 --> 04:53:42,899 >> THANK YOU FOR PUTTING 4878 04:53:42,899 --> 04:53:43,332 TOGETHER EVERYTHING. 4879 04:53:43,332 --> 04:53:44,901 IT WAS AMAZING. 4880 04:53:44,901 --> 04:53:45,635 >> MY PLEASURE. 4881 04:53:45,635 --> 04:53:46,936 LOOK FORWARD TO SEEING EVERYONE 4882 04:53:46,936 --> 04:53:47,270 TOMORROW THEN. 4883 04:53:47,270 --> 04:53:48,638 THANK YOU. 4884 04:53:48,638 --> 04:53:49,038 >> THANK YOU. 4885 04:53:49,038 --> 04:53:49,505 GREAT WORK. 4886 04:53:49,505 --> 04:53:59,505 >> THANK YOU.