1 00:00:05,846 --> 00:00:07,948 IT'S A PLEASURE TO WELCOME 2 00:00:07,948 --> 00:00:13,220 YOU TO ANOTHER SESSION IN THE 3 00:00:13,220 --> 00:00:17,091 22ND YEAR OF A COURSE AT THE 4 00:00:17,091 --> 00:00:18,359 NATIONAL INSTITUTES OF HEALTH IN 5 00:00:18,359 --> 00:00:19,560 BETHESDA, MARYLAND. 6 00:00:19,560 --> 00:00:21,195 THE COURSE IS CALLED 7 00:00:21,195 --> 00:00:26,467 DEMYSTIFYING MEDICINE. 8 00:00:26,467 --> 00:00:29,603 I AM WIN ARIAS, SENIOR SCIENTIST 9 00:00:29,603 --> 00:00:31,238 EMERITUS HERE, AND WITH MY 10 00:00:31,238 --> 00:00:35,309 COLLEAGUE, DAN KASTNER, WE HAVE 11 00:00:35,309 --> 00:00:41,315 PREPARED THIS SERIES OF SESSIONS 12 00:00:41,315 --> 00:00:43,851 FOR 2025, AND WE ARE COMING TO 13 00:00:43,851 --> 00:00:46,654 THE END OF THIS WITHIN THE NEXT 14 00:00:46,654 --> 00:00:49,857 THREE WEEKS. 15 00:00:49,857 --> 00:00:52,159 SO DEMYSTIFYING MEDICINE IS 16 00:00:52,159 --> 00:00:57,831 DIFFERENT FROM MEDICAL GRAND 17 00:00:57,831 --> 00:00:59,033 ROUNDS, IT'S DIFFERENT FROM A 18 00:00:59,033 --> 00:01:00,134 RESEARCH SEMINAR. 19 00:01:00,134 --> 00:01:02,336 ITS INTENT IS TO BE A COURSE IN 20 00:01:02,336 --> 00:01:03,203 BRIDGE-BUILDING. 21 00:01:03,203 --> 00:01:04,838 ESSENTIALLY, BRIDGING EXCITING 22 00:01:04,838 --> 00:01:07,908 DEVELOPMENTS IN BIOLOGY, 23 00:01:07,908 --> 00:01:10,344 ENGINEERING AND COMPUTER 24 00:01:10,344 --> 00:01:14,081 SCIENCES WITH MEDICINE AND 25 00:01:14,081 --> 00:01:17,651 PUBLIC HEALTH. 26 00:01:17,651 --> 00:01:20,087 THE COURSE IS HELD FROM 3:00 TO 27 00:01:20,087 --> 00:01:24,558 5:00 P.M. EASTERN STANDARD TIME, 28 00:01:24,558 --> 00:01:27,194 FROM JANUARY THROUGH MAY. 29 00:01:27,194 --> 00:01:33,534 IT CAN BE WATCHED ON THE WEBSITE 30 00:01:33,534 --> 00:01:37,137 INDICATED HERE, 31 00:01:37,137 --> 00:01:38,572 VIDEOCAST.NIH.GOV. 32 00:01:38,572 --> 00:01:41,408 FOR THOSE SEEKING CME CREDIT, 33 00:01:41,408 --> 00:01:51,919 THE CODE FOR TODAY IS 58793. 34 00:01:51,919 --> 00:01:53,454 NOW MOST IMPORTANTLY DURING THE 35 00:01:53,454 --> 00:01:54,755 COURSE OF THESE PRESENTATIONS 36 00:01:54,755 --> 00:01:56,390 TODAY, WE ENCOURAGE ALL OF YOU 37 00:01:56,390 --> 00:01:59,994 TO SUBMIT QUESTIONS, AND YOU CAN 38 00:01:59,994 --> 00:02:03,297 DO THIS USING THE "SEND LIVE 39 00:02:03,297 --> 00:02:04,865 FEEDBACK" ON YOUR VIDEOCAST 40 00:02:04,865 --> 00:02:06,667 DISPLAY. 41 00:02:06,667 --> 00:02:09,837 THESE QUESTIONS WILL THEN FORM 42 00:02:09,837 --> 00:02:13,974 THE BASIS OF WHAT IS INVARIABLY 43 00:02:13,974 --> 00:02:15,642 A VERY ACTIVE INTERCHANGE 44 00:02:15,642 --> 00:02:18,379 BETWEEN THE SPEAKERS, THE 45 00:02:18,379 --> 00:02:22,216 WORLDWIDE ATTENDEES, AND AMONGST 46 00:02:22,216 --> 00:02:27,221 THE SPEAKERS THEMSELVES AT THE 47 00:02:27,221 --> 00:02:28,288 CONCLUSION OF THE TWO 48 00:02:28,288 --> 00:02:30,824 PRESENTATIONS. 49 00:02:30,824 --> 00:02:32,526 NOW I CALL YOUR ATTENTION TO THE 50 00:02:32,526 --> 00:02:34,661 FACT THAT ALL PREVIOUS SESSIONS 51 00:02:34,661 --> 00:02:39,033 FOR THE PAST 23 YEARS ARE 52 00:02:39,033 --> 00:02:42,736 AVAILABLE ON THE LINKS I'VE 53 00:02:42,736 --> 00:02:45,606 SHOWN ON THIS SLIDE, AND YOU CAN 54 00:02:45,606 --> 00:02:48,242 ACCESS THEM AT ANY TIME. 55 00:02:48,242 --> 00:02:54,348 IF YOU HAVE ANY ADDITIONAL 56 00:02:54,348 --> 00:02:56,550 INFORMATION OR REQUEST FOR 57 00:02:56,550 --> 00:02:58,185 INFORMING, COMMUNICATE WITH US 58 00:02:58,185 --> 00:03:02,790 AT DEMYSTIFYINGMED@NIH.GOV. 59 00:03:02,790 --> 00:03:04,525 NOW THE PICTURES ON THE RIGHT 60 00:03:04,525 --> 00:03:07,261 SIDE OF THIS SLIDE ARE TWO. 61 00:03:07,261 --> 00:03:13,801 ONE IS A SILO, WHICH REPRESENTS 62 00:03:13,801 --> 00:03:16,136 THE IDEA THAT MUCH OF THE 63 00:03:16,136 --> 00:03:16,770 EXCITING DEVELOPMENTAL 64 00:03:16,770 --> 00:03:18,972 DEVELOPING INFORMATION IS SORT 65 00:03:18,972 --> 00:03:21,041 OF LOCKED AWAY FROM ONE ANOTHER. 66 00:03:21,041 --> 00:03:22,776 IT'S SORT OF LIKE SEPARATE 67 00:03:22,776 --> 00:03:25,312 PIECES OF A PIZZA PIE. 68 00:03:25,312 --> 00:03:27,948 WHAT WE SEEK TO DO IS IN THE 69 00:03:27,948 --> 00:03:28,816 UPPER RIGHT. 70 00:03:28,816 --> 00:03:32,186 AND THAT IS TO BRIDGE THESE GAPS 71 00:03:32,186 --> 00:03:36,790 AND, FOR EXAMPLE, IN THIS 72 00:03:36,790 --> 00:03:37,658 EXCELLENT PHOTOGRAPH OF THE 73 00:03:37,658 --> 00:03:41,395 CONSTRUCTION OF THE BROOKLYN 74 00:03:41,395 --> 00:03:42,596 BRIDGE, TWO INDIVIDUALS, 75 00:03:42,596 --> 00:03:44,064 PRESUMABLY ONE FROM BROOKLYN AND 76 00:03:44,064 --> 00:03:46,200 ONE FROM MANHATTAN, ARE MEETING 77 00:03:46,200 --> 00:03:52,439 ON THE CATWALK TO EXCHANGE THEIR 78 00:03:52,439 --> 00:03:55,075 OWN BEDS OF ADVANCED 79 00:03:55,075 --> 00:03:55,609 INFORMATION. 80 00:03:55,609 --> 00:03:58,245 IN EFFECT, THAT'S WHAT 81 00:03:58,245 --> 00:03:59,113 DEMYSTIFYING MEDICINE IS. 82 00:03:59,113 --> 00:04:00,314 YOU WILL SEE THAT THROUGH THE 83 00:04:00,314 --> 00:04:03,050 YEARS, WE HAVE TOUCHED ON WIDE 84 00:04:03,050 --> 00:04:06,887 AREAS OF BIOLOGY FROM THE ORIGIN 85 00:04:06,887 --> 00:04:12,126 OF LIFE TO PROBLEMS OF BIOLOGY 86 00:04:12,126 --> 00:04:14,962 IN SPACE TO THE IMPACT OF THE 87 00:04:14,962 --> 00:04:16,964 GENETIC AND MOLECULAR 88 00:04:16,964 --> 00:04:18,565 REVOLUTION, AND WITH 89 00:04:18,565 --> 00:04:21,735 PRESENTATION OF PATIENTS 90 00:04:21,735 --> 00:04:22,836 FREQUENTLY WHEN POSSIBLE TO 91 00:04:22,836 --> 00:04:27,307 ILLUSTRATE THE GOAL OF ALL OF 92 00:04:27,307 --> 00:04:30,811 THIS RESEARCH. 93 00:04:30,811 --> 00:04:35,849 NOW, TODAY'S TOPIC DEALS WITH 94 00:04:35,849 --> 00:04:37,284 SOMETHING WE HAVE NOT DISCUSSED 95 00:04:37,284 --> 00:04:37,951 BEFORE. 96 00:04:37,951 --> 00:04:39,686 AND THAT IS CONGENITAL HEART 97 00:04:39,686 --> 00:04:44,057 DISEASE. 98 00:04:44,057 --> 00:04:48,662 THE NIH HAS PLAYED A SIGNIFICANT 99 00:04:48,662 --> 00:04:50,631 ROLE IN UNDERSTANDING CONGENITAL 100 00:04:50,631 --> 00:04:53,500 HEART DISEASE THROUGHOUT THE 101 00:04:53,500 --> 00:04:57,938 YEARS, IN LARGE PART BY 102 00:04:57,938 --> 00:05:00,674 SUPPORTING WORK NOT ON THE 103 00:05:00,674 --> 00:05:02,543 INTRAMURAL CAMPUS BUT SOME. 104 00:05:02,543 --> 00:05:06,380 SO IN A VERY SIMPLISTIC WAY FOR 105 00:05:06,380 --> 00:05:09,216 THE ULTIMATE MOLECULAR 106 00:05:09,216 --> 00:05:11,852 BIOLOGIST, LET US REMEMBER THAT 107 00:05:11,852 --> 00:05:16,123 THE HEART IS A FOUR CHAMBERED 108 00:05:16,123 --> 00:05:17,958 PUMP. 109 00:05:17,958 --> 00:05:21,028 VENOUS BLOOD FLOWS INTO RIGHT 110 00:05:21,028 --> 00:05:23,764 CHAMBER EN ROUTE TO THE LUNG FOR 111 00:05:23,764 --> 00:05:25,199 OXYGENATION, AND THEN THEY PASS 112 00:05:25,199 --> 00:05:29,136 THROUGH THE LEFT HEART INTO THE 113 00:05:29,136 --> 00:05:31,138 PERIPHERY VIA THE ARTERIAL 114 00:05:31,138 --> 00:05:33,307 CIRCULATION. 115 00:05:33,307 --> 00:05:35,375 NOW THERE WERE MANY CONGENITAL 116 00:05:35,375 --> 00:05:41,381 DEFECTS THAT OCCUR INVOLVING 117 00:05:41,381 --> 00:05:43,984 ABNORMAL CONNECTIONS OF VESSELS, 118 00:05:43,984 --> 00:05:45,185 ABNORMAL CONNECTIONS BETWEEN 119 00:05:45,185 --> 00:05:50,023 INDIVIDUAL CHAMBERS, STENOSIS OF 120 00:05:50,023 --> 00:05:52,859 VARIOUS VESSELS, AND OTHERS. 121 00:05:52,859 --> 00:05:54,928 AND ALL OF THOSE ONE WAY OR 122 00:05:54,928 --> 00:05:59,333 ANOTHER IMPAIR OXYGENATION, AND 123 00:05:59,333 --> 00:06:00,968 FREQUENTLY THE VICTIMS ARE 124 00:06:00,968 --> 00:06:03,470 CYANOTIC, THAT IS, THEY LOOK 125 00:06:03,470 --> 00:06:05,672 BLUE BECAUSE THEIR BLOOD IS NOT 126 00:06:05,672 --> 00:06:07,174 OXYGENATED, AND THEY HAVE 127 00:06:07,174 --> 00:06:11,445 LIFE-THREATENING DISEASES. 128 00:06:11,445 --> 00:06:12,546 AND FOR MANY IN THE PAST, PRIOR 129 00:06:12,546 --> 00:06:17,951 TO THE 1950s, MANY FACED EARLY 130 00:06:17,951 --> 00:06:19,219 DEATH. 131 00:06:19,219 --> 00:06:24,157 SO THESE ARE ALL YOUNG CHILDREN. 132 00:06:24,157 --> 00:06:26,526 IT IS SAID THAT THE FIRST 133 00:06:26,526 --> 00:06:29,529 ANATOMIC DESCRIPTION OF THE 134 00:06:29,529 --> 00:06:30,697 VARIOUS CONGENITAL HEART 135 00:06:30,697 --> 00:06:31,798 DISEASES OR AT LEAST SOME OF 136 00:06:31,798 --> 00:06:37,804 THEM GOES BACK TO D DEVINCI IN E 137 00:06:37,804 --> 00:06:38,472 15TH CENTURY. 138 00:06:38,472 --> 00:06:40,440 AT ANY RATE, IT WASN'T UNTIL THE 139 00:06:40,440 --> 00:06:44,378 1930s THAT A REMARKABLE WOMAN, 140 00:06:44,378 --> 00:06:47,648 HELEN TAUSIG, SET UP THE FIRST 141 00:06:47,648 --> 00:06:52,019 PEDIATRIC CARDIOLOGY CENTER, AND 142 00:06:52,019 --> 00:06:53,654 THIS WELCOMED PATIENTS, ALTHOUGH 143 00:06:53,654 --> 00:06:59,493 THERE WASN'T MUCH THAT COULD BE 144 00:06:59,493 --> 00:07:01,028 DONE FOR THEM THAT WAS 145 00:07:01,028 --> 00:07:01,795 DEFINITIVE. 146 00:07:01,795 --> 00:07:02,663 THE FIRST ADVANCE IN THAT TOOK 147 00:07:02,663 --> 00:07:06,600 PLACE IN 1938, WHEN THE SURGERY 148 00:07:06,600 --> 00:07:10,971 WAS PERFORMED FOR ONE OF THE 149 00:07:10,971 --> 00:07:13,273 CONGENITAL HEART DISORDERS WE'LL 150 00:07:13,273 --> 00:07:14,941 HEAR ABOUT, BUT THE SURGERY, OF 151 00:07:14,941 --> 00:07:17,978 COURSE, WAS EXTREMELY 152 00:07:17,978 --> 00:07:21,148 CHALLENGING BECAUSE WHAT DO YOU 153 00:07:21,148 --> 00:07:22,783 DO WITH THE ONGOING CIRCULATION 154 00:07:22,783 --> 00:07:24,217 IF YOU'RE ACTUALLY OPERATING ON 155 00:07:24,217 --> 00:07:27,387 A HEART? 156 00:07:27,387 --> 00:07:28,355 AND OF COURSE THE CHEST HAD TO 157 00:07:28,355 --> 00:07:29,022 BE OPENED. 158 00:07:29,022 --> 00:07:31,758 IT WAS A VERY DANGEROUS AND 159 00:07:31,758 --> 00:07:33,427 ALMOST HEROIC CHALLENGE. 160 00:07:33,427 --> 00:07:35,262 BUT THE BIG BREAKTHROUGH TOOK 161 00:07:35,262 --> 00:07:40,734 PLACE IN AROUND 1950, WITH THE 162 00:07:40,734 --> 00:07:42,536 DEVELOPMENT OF MACHINES, THE 163 00:07:42,536 --> 00:07:43,704 HEART LUNG MACHINE OR ALSO KNOWN 164 00:07:43,704 --> 00:07:49,376 AS THE CARDIOPULMONARY BYPASS, 165 00:07:49,376 --> 00:07:51,678 IN WHICH BLOOD COULD BYPASS THE 166 00:07:51,678 --> 00:07:54,081 HEART AND HENCE THE SURGEON 167 00:07:54,081 --> 00:07:57,784 PRETTY MUCH HAD A DRY FIELD IN 168 00:07:57,784 --> 00:07:59,553 WHICH TO CONDUCT MORE EXPANSIVE 169 00:07:59,553 --> 00:08:01,755 SURGERY. 170 00:08:01,755 --> 00:08:03,924 AND HERE THE SUCCESSES WERE 171 00:08:03,924 --> 00:08:05,325 SUBSTANTIAL. 172 00:08:05,325 --> 00:08:09,496 AND SURVIVAL WAS GREATLY 173 00:08:09,496 --> 00:08:10,697 INCREASED. 174 00:08:10,697 --> 00:08:12,232 SOMETIMES COMPLETELY NORMAL 175 00:08:12,232 --> 00:08:16,503 LIVES RESULTED. 176 00:08:16,503 --> 00:08:18,705 AND THE SPECIALTY OF CONGENITAL 177 00:08:18,705 --> 00:08:21,208 HEART DISEASE BECAME A REALITY. 178 00:08:21,208 --> 00:08:22,709 THIS OF COURSE WAS ENHANCED BY 179 00:08:22,709 --> 00:08:27,114 THE DEVELOPMENT OF IMAGING 180 00:08:27,114 --> 00:08:28,548 TECHNIQUES, AND IN MORE RECENT 181 00:08:28,548 --> 00:08:29,950 TIMES, THE AMAZING DEVELOPMENT 182 00:08:29,950 --> 00:08:33,153 OF SURGERY DONE IN AND ON THE 183 00:08:33,153 --> 00:08:36,089 HEART USING CATHETERS, WHICH ARE 184 00:08:36,089 --> 00:08:39,359 PASSED THROUGH THE CIRCULATION, 185 00:08:39,359 --> 00:08:43,296 AND AVOIDING THE NECESSITY FOR 186 00:08:43,296 --> 00:08:47,234 MAJOR OPENING UP OF THE CHEST TO 187 00:08:47,234 --> 00:08:49,002 OPERATE DIRECTLY. 188 00:08:49,002 --> 00:08:51,738 NOW WITH THESE GREAT ADVANCES, 189 00:08:51,738 --> 00:08:53,907 PROBLEMS HAVE OCCURRED. 190 00:08:53,907 --> 00:08:58,378 AND THE FOCUS IN SOME OF THESE 191 00:08:58,378 --> 00:09:00,814 INSTANCES HAS BEEN ON LONG-TERM 192 00:09:00,814 --> 00:09:04,751 PROBLEMS, PROBLEMS THAT DEVELOP 193 00:09:04,751 --> 00:09:07,687 SOMETIMES PROGRESSIVELY OVER 194 00:09:07,687 --> 00:09:10,424 YEARS AFTER SUCCESSFUL SURGERY. 195 00:09:10,424 --> 00:09:12,626 AND THAT'S THE SUBJECT OF 196 00:09:12,626 --> 00:09:20,500 TODAY'S TOPIC, BRIDGING SUCCESS 197 00:09:20,500 --> 00:09:20,934 WITH CHALLENGE. 198 00:09:20,934 --> 00:09:23,670 AND I LIKE THE QUOTE FROM A 199 00:09:23,670 --> 00:09:25,205 DANISH CARTOONIST WHO WROTE 200 00:09:25,205 --> 00:09:29,443 YEARS AGO, "PROBLEMS WORTHY OF 201 00:09:29,443 --> 00:09:33,380 ATTACK PROVE THEIR WORTH BY 202 00:09:33,380 --> 00:09:34,281 STRIKING BACK." 203 00:09:34,281 --> 00:09:37,017 NOW OUR FIRST SPEAKER TODAY IS 204 00:09:37,017 --> 00:09:41,254 TOM BURKLOW, WHO GOT HIS 205 00:09:41,254 --> 00:09:42,322 MEDICAL DEGREE FROM WASHINGTON 206 00:09:42,322 --> 00:09:44,558 UNIVERSITY IN ST. LOUIS. 207 00:09:44,558 --> 00:09:48,829 HE DID A PEDIATRIC RESIDENCY AT 208 00:09:48,829 --> 00:09:50,464 WALTER REED ARMY MEDICAL CENTER, 209 00:09:50,464 --> 00:09:53,533 AND THEN A PEDIATRIC CARDIAC -- 210 00:09:53,533 --> 00:09:55,769 CARDIOLOGY FELLOWSHIP AT THE 211 00:09:55,769 --> 00:09:56,903 CHILDREN'S NATIONAL HOSPITAL IN 212 00:09:56,903 --> 00:09:59,539 WASHINGTON. 213 00:09:59,539 --> 00:10:04,778 TOM SERVED FOR 30 YEARS IN ARMY 214 00:10:04,778 --> 00:10:07,180 MEDICINE, INCLUDING BEING CHIEF 215 00:10:07,180 --> 00:10:11,785 OF PEDIATRICS FROM 2003 TO 2011 216 00:10:11,785 --> 00:10:13,987 AT THE WALTER REED NATIONAL 217 00:10:13,987 --> 00:10:16,389 MILITARY MEDICAL CENTER, WHERE 218 00:10:16,389 --> 00:10:18,892 HE BECAME INCREASINGLY ENGAGED 219 00:10:18,892 --> 00:10:20,894 IN UNDERGRADUATE AND GRADUATE 220 00:10:20,894 --> 00:10:24,464 MEDICAL EDUCATION. 221 00:10:24,464 --> 00:10:26,666 HE WAS THE DIRECTOR FOR 222 00:10:26,666 --> 00:10:28,969 HEALTHCARE OPERATIONS AND 223 00:10:28,969 --> 00:10:32,372 POPULATION HEALTH PROGRAMS, AND 224 00:10:32,372 --> 00:10:35,075 DURING HIS CAREER WAS DEPLOYED 225 00:10:35,075 --> 00:10:37,377 TO SAUDI ARABIA, KUWAIT, AND 226 00:10:37,377 --> 00:10:40,680 IRAQ. 227 00:10:40,680 --> 00:10:43,483 IN 2017, HE JOINED THE NIH, 228 00:10:43,483 --> 00:10:45,151 WHERE HE IS CURRENTLY THE 229 00:10:45,151 --> 00:10:48,221 DIRECTOR FOR EDUCATION AND 230 00:10:48,221 --> 00:10:51,324 TRAINING AT THE NIH CLINICAL 231 00:10:51,324 --> 00:10:51,858 CENTER. 232 00:10:51,858 --> 00:10:54,761 THIS IS A REMARKABLE 233 00:10:54,761 --> 00:10:57,063 INSTITUTION, AND THE PROGRAM HE 234 00:10:57,063 --> 00:10:59,900 DIRECTS OVERSEES A PORTFOLIO OF 235 00:10:59,900 --> 00:11:04,070 TRAINING AND EDUCATION PROGRAMS, 236 00:11:04,070 --> 00:11:05,839 WHICH INCLUDE CONTINUING MEDICAL 237 00:11:05,839 --> 00:11:09,309 EDUCATION ACTIVITIES, GRADUATE 238 00:11:09,309 --> 00:11:12,712 MEDICAL EDUCATION, AND THE 239 00:11:12,712 --> 00:11:15,315 HEALTHCARE SIMULATION TRAINING 240 00:11:15,315 --> 00:11:18,084 PROGRAM, AND A REMARKABLE 241 00:11:18,084 --> 00:11:19,185 UNDERGRADUATE MEDICAL STUDENT 242 00:11:19,185 --> 00:11:24,624 RESEARCH TRAINING PROGRAM, WHICH 243 00:11:24,624 --> 00:11:25,825 IS A MODEL FOR THE WORLD. 244 00:11:25,825 --> 00:11:29,563 IT'S CALLED THE MEDICAL RESEARCH 245 00:11:29,563 --> 00:11:31,965 SCHOLARS PROGRAM, WHERE ABOUT 50 246 00:11:31,965 --> 00:11:33,166 MEDICAL STUDENTS ARE SELECTED ON 247 00:11:33,166 --> 00:11:37,771 A COMPETITIVE BASIS TO SPEND A 248 00:11:37,771 --> 00:11:39,839 YEAR ON THE BETHESDA CAMPUS 249 00:11:39,839 --> 00:11:42,909 DOING BASIC TRANSLATIONAL OR 250 00:11:42,909 --> 00:11:47,047 LINKED RESEARCH. 251 00:11:47,047 --> 00:11:49,015 TOM IS A BOARD CERTIFIED 252 00:11:49,015 --> 00:11:50,016 PEDIATRIC CARDIOLOGIST, AND HE 253 00:11:50,016 --> 00:11:51,985 HAS A JOINT NATIONAL HEART, LUNG 254 00:11:51,985 --> 00:11:54,487 AND BLOOD INSTITUTE APPOINTMENT 255 00:11:54,487 --> 00:11:56,890 AS CHIEF OF PEDIATRIC 256 00:11:56,890 --> 00:11:58,091 CARDIOLOGY. 257 00:11:58,091 --> 00:12:01,595 AS PART OF THE CONSULT SERVICE 258 00:12:01,595 --> 00:12:05,999 OF THE NIH CARDIOLOGY CENTER. 259 00:12:05,999 --> 00:12:09,169 SO TOM IS GOING TO BE THE FIRST 260 00:12:09,169 --> 00:12:11,338 SPEAKER AND WILL EDUCATE US ALL 261 00:12:11,338 --> 00:12:14,641 ABOUT THE ISSUES AND THE NATURE 262 00:12:14,641 --> 00:12:17,110 OF THE PROBLEMS OF CONGENITAL 263 00:12:17,110 --> 00:12:22,215 HEART DISEASE. 264 00:12:22,215 --> 00:12:26,486 THE SECOND SPEAKER IS THEO 265 00:12:26,486 --> 00:12:27,454 HELLER. 266 00:12:27,454 --> 00:12:29,222 SO THEO GOT HIS MEDICAL DEGREE 267 00:12:29,222 --> 00:12:30,523 IN SOUTH AFRICA FROM THE 268 00:12:30,523 --> 00:12:39,165 UNIVERSITY OF WITWATERSRAND, A 269 00:12:39,165 --> 00:12:40,900 RESIDENCY IN GEORGETOWN, A 270 00:12:40,900 --> 00:12:43,103 FELLOWSHIP IN HEPATITIS VIRUSES 271 00:12:43,103 --> 00:12:48,141 HERE AT NIAID, AND THEN A 272 00:12:48,141 --> 00:12:49,542 GASTROENTEROLOGY HEPATOLOGY 273 00:12:49,542 --> 00:12:50,744 FELLOWSHIP AT THE UNIVERSITY OF 274 00:12:50,744 --> 00:12:52,512 MARYLAND MEDICAL CENTER. 275 00:12:52,512 --> 00:12:54,814 AND A HEPATOLOGY FELLOWSHIP THEN 276 00:12:54,814 --> 00:12:59,853 HERE ON THE NIH CAMPUS. 277 00:12:59,853 --> 00:13:04,858 THEO IS A SECTION CHIEF OF THE 278 00:13:04,858 --> 00:13:07,060 TRANSLATIONAL HEPATOLOGY SECTION 279 00:13:07,060 --> 00:13:09,396 OF THE LIVER DISEASE BRANCH OF 280 00:13:09,396 --> 00:13:12,866 THE NATIONAL INSTITUTE OF 281 00:13:12,866 --> 00:13:14,834 DIABETES AND DIGESTIVE KIDNEY 282 00:13:14,834 --> 00:13:15,268 DISEASE. 283 00:13:15,268 --> 00:13:17,671 HE'S A SENIOR INVESTIGATOR, AND 284 00:13:17,671 --> 00:13:20,206 THE CLINICAL RESEARCH -- IN THE 285 00:13:20,206 --> 00:13:21,074 CLINICAL RESEARCH SECTION. 286 00:13:21,074 --> 00:13:23,576 NOW HIS INTERESTS ARE BROAD AND 287 00:13:23,576 --> 00:13:30,316 THEY INCLUDE MANY APPROACHES, A 288 00:13:30,316 --> 00:13:31,818 LOT OF COLLABORATIVE WORK, BUT 289 00:13:31,818 --> 00:13:33,787 HIS UNDERLYING THESIS, I THINK 290 00:13:33,787 --> 00:13:35,422 IS SOMEWHAT UNIQUE. 291 00:13:35,422 --> 00:13:38,591 AND HIS RESEARCH HAS BEEN 292 00:13:38,591 --> 00:13:40,026 BRILLIANT IN APPROACHING THIS. 293 00:13:40,026 --> 00:13:43,096 OF HIS THESIS IS THAT ONE CAN 294 00:13:43,096 --> 00:13:51,171 TESS HYPOTHESTEST HYPOTHESES INL 295 00:13:51,171 --> 00:13:52,505 SITUATIONS WITH PATIENTS AND 296 00:13:52,505 --> 00:13:54,140 THEN RESULTS CAN BE ADAPTED INTO 297 00:13:54,140 --> 00:13:55,341 LABORATORY PROJECTS THAT CAN 298 00:13:55,341 --> 00:13:58,945 LEAD TO FUNDAMENTAL BIOLOGIC 299 00:13:58,945 --> 00:14:01,247 INSIGHTS AND BETTER DIAGNOSIS 300 00:14:01,247 --> 00:14:06,152 AND MANAGEMENT. 301 00:14:06,152 --> 00:14:09,222 THIS IS A CHALLENGE FOR CLINICAL 302 00:14:09,222 --> 00:14:09,989 INVESTIGATION AND ONE IN WHICH 303 00:14:09,989 --> 00:14:12,625 HE HAS CARRIED OUT BRILLIANTLY, 304 00:14:12,625 --> 00:14:18,531 FOCUSING IN AREAS OF CLINICAL 305 00:14:18,531 --> 00:14:19,733 RESEARCH, INFECTIOUS DISEASES, 306 00:14:19,733 --> 00:14:21,134 SYSTEMS ANALYSIS, MOLECULAR 307 00:14:21,134 --> 00:14:27,807 BIOLOGY, AND BIOCHEMISTRY. 308 00:14:27,807 --> 00:14:30,343 THEO IS GOING TO DISCUSS THE 309 00:14:30,343 --> 00:14:34,047 EFFECTS OF AT LEAST ONE MAJOR 310 00:14:34,047 --> 00:14:37,217 FORM OF SURGERY FOR CONGENITAL 311 00:14:37,217 --> 00:14:39,319 HEART DISEASE, THE EFFECTS ON 312 00:14:39,319 --> 00:14:41,921 THE LIVER, WHICH CAN CREATE A 313 00:14:41,921 --> 00:14:46,092 VERY SERIOUS PROBLEM AND WAS NOT 314 00:14:46,092 --> 00:14:49,462 FULLY ANTICIPATED. 315 00:14:49,462 --> 00:14:52,966 SO PLEASE SEND IN YOUR QUESTIONS 316 00:14:52,966 --> 00:14:54,300 DURING THE PRESENTATIONS, AND 317 00:14:54,300 --> 00:15:01,074 NOW OUR FIRST SPEAKER. 318 00:15:01,074 --> 00:15:02,308 TOM, IT'S ALL YOURS. 319 00:15:02,308 --> 00:15:04,344 >> THANK YOU, DR. AIR JUST. 320 00:15:04,344 --> 00:15:08,348 T ARIAS.THANK YOU FOR YOUR GENES 321 00:15:08,348 --> 00:15:10,383 INTRODUCTION AND BOTH THEO AND I 322 00:15:10,383 --> 00:15:11,918 REALLY APPRECIATE THE 323 00:15:11,918 --> 00:15:14,521 OPPORTUNITY TO SHARE THIS 324 00:15:14,521 --> 00:15:14,854 INFORMATION. 325 00:15:14,854 --> 00:15:18,691 I WANT TO THANK DR. KASTNER, 326 00:15:18,691 --> 00:15:19,459 CO-DIRECTOR, THANK YOU FOR 327 00:15:19,459 --> 00:15:20,960 SUPPORTING US THROUGH THIS AND 328 00:15:20,960 --> 00:15:22,295 ESPECIALLY I WANT TO GIVE AN 329 00:15:22,295 --> 00:15:26,332 EARLY SHOUT OUT TO A PATIENT AND 330 00:15:26,332 --> 00:15:27,667 HER MOTHER WHO WILL BE JOINING 331 00:15:27,667 --> 00:15:28,735 US AS WELL. 332 00:15:28,735 --> 00:15:35,942 AND THIS IS A PATIENT OF BOTH 333 00:15:35,942 --> 00:15:37,277 DR. -- I'M GOING TO DO THE MOST 334 00:15:37,277 --> 00:15:38,678 DIFFICULT THING HERE IN THE 20TH 335 00:15:38,678 --> 00:15:43,016 CENTURY AND SEE IF I CAN SHARE. 336 00:15:43,016 --> 00:15:43,950 MY PRESENTATION WITHOUT LOGGING 337 00:15:43,950 --> 00:15:54,027 OFF. 338 00:16:02,502 --> 00:16:02,869 ALL RIGHT. 339 00:16:02,869 --> 00:16:13,146 IS IT COMING UP? 340 00:16:19,752 --> 00:16:20,253 SO AGAIN THANK YOU. 341 00:16:20,253 --> 00:16:22,222 WE'RE GOING TO ACTUALLY DELVE 342 00:16:22,222 --> 00:16:25,692 INTO A LITTLE MORE COMPLEX 343 00:16:25,692 --> 00:16:26,593 ASPECT OF GENERAL HEART DISEASE 344 00:16:26,593 --> 00:16:28,328 AND PUT THIS UNDER THE UMBRELLA 345 00:16:28,328 --> 00:16:29,863 OF WHAT WE CALL THE SINGLE 346 00:16:29,863 --> 00:16:30,263 VENTRICLE. 347 00:16:30,263 --> 00:16:32,599 IN ADDITION, WE'RE GOING TO 348 00:16:32,599 --> 00:16:36,002 DELVE INTO HOW THIS IS ADDRESSED 349 00:16:36,002 --> 00:16:38,404 FROM A SURGICAL PERSPECTIVE. 350 00:16:38,404 --> 00:16:47,380 WITH THAT, I'M GOING TO -- SO 351 00:16:47,380 --> 00:16:49,082 THE OBJECTIVES FOR MY PART OF 352 00:16:49,082 --> 00:16:50,750 THE PRESENTATION, THIS IS TO LAY 353 00:16:50,750 --> 00:16:55,455 A FOUNDATION AND BACKGROUND FOR 354 00:16:55,455 --> 00:16:56,222 DR. HELLER'S PRESENTATION. 355 00:16:56,222 --> 00:16:59,192 WHAT I WANT DO IS GO THROUGH 356 00:16:59,192 --> 00:17:02,662 QUICKLY TO DESCRIBE THE ANATOMY 357 00:17:02,662 --> 00:17:03,997 AND PHYSIOLOGY OF THE NORMAL 358 00:17:03,997 --> 00:17:05,431 HEART AND CARDIOVASCULAR SYSTEM. 359 00:17:05,431 --> 00:17:07,834 WE'RE GOING TO TALK ABOUT HOW 360 00:17:07,834 --> 00:17:09,335 SURGICAL PALLIATION OF 361 00:17:09,335 --> 00:17:10,303 CONGENITAL HEART DISEASE WITH 362 00:17:10,303 --> 00:17:12,071 ONE DOMINANT VENTRICLE, THAT IS 363 00:17:12,071 --> 00:17:17,677 WHAT'S CALLED A FONTAN 364 00:17:17,677 --> 00:17:18,945 PALLIATION MAY IMPART NORMAL 365 00:17:18,945 --> 00:17:19,312 CIRCULATION. 366 00:17:19,312 --> 00:17:20,413 THEN WE'RE GOING TO SEGUE AT THE 367 00:17:20,413 --> 00:17:26,085 END TO ILLUSTRATE HOW FONTAN 368 00:17:26,085 --> 00:17:28,488 PALLIATION PROGRESSIVELY RESULTS 369 00:17:28,488 --> 00:17:29,722 IN LONG TERM DISEASE. 370 00:17:29,722 --> 00:17:31,557 AS FAR AS DISCLOSURES, SADLY, I 371 00:17:31,557 --> 00:17:36,930 HAVE NONE. 372 00:17:36,930 --> 00:17:38,498 SO ARISTOTLE IDENTIFIED THE 373 00:17:38,498 --> 00:17:39,766 HEART AS THE MOST IMPORTANT 374 00:17:39,766 --> 00:17:40,967 ORGAN OF THE BODY. 375 00:17:40,967 --> 00:17:42,268 DR. HILL WOULD PROBABLY OBJECT 376 00:17:42,268 --> 00:17:44,037 BUT THE MOST IMPORTANT ORGAN OF 377 00:17:44,037 --> 00:17:45,238 THE BODY, BEING THE FIRST THAT 378 00:17:45,238 --> 00:17:50,276 HE OBSERVED TO -- CHICKEN 379 00:17:50,276 --> 00:17:51,778 EMBRYOS, HE FELT IT WAS THE SEED 380 00:17:51,778 --> 00:17:54,080 OF INTELLIGENCE, EMOTION, AND 381 00:17:54,080 --> 00:17:56,482 SENSATION, AS HE DESCRIBED IT AS 382 00:17:56,482 --> 00:18:00,320 A HOT DRY ORGAN, AND ALL THE 383 00:18:00,320 --> 00:18:01,955 OTHER ORGANS SURROUNDING IT, 384 00:18:01,955 --> 00:18:05,358 BRAIN, LUNG, SIMPLY EXISTED TO 385 00:18:05,358 --> 00:18:11,064 COOL THE LIVER. 386 00:18:11,064 --> 00:18:12,899 CONGENITAL HEART DISEASE AFFECTS 387 00:18:12,899 --> 00:18:14,934 1% OF ALL LIVE BIRTHS, SO IN THE 388 00:18:14,934 --> 00:18:17,704 UNITED STATES, ABOUT 40,000 389 00:18:17,704 --> 00:18:19,138 BABIES PER YEAR ARE BORN WITH 390 00:18:19,138 --> 00:18:21,975 SOME TYPE OF HEART DISEASE. 391 00:18:21,975 --> 00:18:24,711 OF THOSE WHO ARE BORN, ABOUT 25% 392 00:18:24,711 --> 00:18:30,416 OF THEM REQUIRED SOME SORT OF 393 00:18:30,416 --> 00:18:31,317 INTERVENTION OR CATH PROCEDURE 394 00:18:31,317 --> 00:18:33,686 IN THE FIRST YEAR OF LIFE. 395 00:18:33,686 --> 00:18:34,687 CONSEQUENTLY, HEART DISEASE IS 396 00:18:34,687 --> 00:18:36,089 RESPONSIBLE FOR THE LARGEST 397 00:18:36,089 --> 00:18:38,491 PORTION OF MORTALITY RESULTING 398 00:18:38,491 --> 00:18:39,926 FROM BIRTH DEFECTS TODAY AND 399 00:18:39,926 --> 00:18:41,461 IT'S THE MOST COMMON 400 00:18:41,461 --> 00:18:43,196 NON-INFECTIOUS CAUSE OF DEATH IN 401 00:18:43,196 --> 00:18:44,230 INFANTS, AND OVERALL, IF YOU 402 00:18:44,230 --> 00:18:46,065 LOOK AT THE OVERALL MORTALITY, 403 00:18:46,065 --> 00:18:48,001 IT ACCOUNTS FOR -- THIS IS BOTH 404 00:18:48,001 --> 00:18:50,970 ADULTS AND PEDIATRICS, PROBABLY 405 00:18:50,970 --> 00:18:54,040 ABOUT .21% OF ALL MORTALITY IN 406 00:18:54,040 --> 00:18:58,511 THE UNITED STATES TODAY. 407 00:18:58,511 --> 00:19:02,448 BEGINNING WITH LANDMARK WORK 408 00:19:02,448 --> 00:19:03,883 INTO 1930 THAT DR. ARIAS HAD 409 00:19:03,883 --> 00:19:08,021 REFERRED TO, WITH ADVANCES IN 410 00:19:08,021 --> 00:19:09,889 DIAGNOSTICS AND THERAPEUTIC 411 00:19:09,889 --> 00:19:10,656 INTERVENTIONS, ESPECIALLY 412 00:19:10,656 --> 00:19:13,159 THROUGH SURGERY AND EVENTUAL 413 00:19:13,159 --> 00:19:15,028 CARDIAC CATHETERIZATION, 414 00:19:15,028 --> 00:19:19,399 CONGENITAL HEART DISEASE RELATED 415 00:19:19,399 --> 00:19:22,301 MORTALITY WITH SUCCESS OF THE 416 00:19:22,301 --> 00:19:25,438 FIRST COHORT IMPROVING AND 417 00:19:25,438 --> 00:19:30,243 DECLINE IN CHILD MORTALITY OF 418 00:19:30,243 --> 00:19:32,078 FUTURE GENERATIONS. 419 00:19:32,078 --> 00:19:35,248 NOW AT THE BEGINNING, MOST 420 00:19:35,248 --> 00:19:35,915 MORTALITY SEEN WITH HEART 421 00:19:35,915 --> 00:19:38,117 DISEASE IS SHOWN IN BLUE HERE 422 00:19:38,117 --> 00:19:40,853 OCCURRED IN CHILDREN WHO ARE 423 00:19:40,853 --> 00:19:42,221 LESS THAN ONE YEARS OF AGE BUT 424 00:19:42,221 --> 00:19:44,223 IF YOU LOOK AT THE MOST RECENT 425 00:19:44,223 --> 00:19:46,426 COHORT, YOU CAN SEE NOW THAT 426 00:19:46,426 --> 00:19:48,594 INFANT DEATHS ACTUALLY ARE 427 00:19:48,594 --> 00:19:49,796 MARKEDLY LESS COMMON AND WE SEE 428 00:19:49,796 --> 00:19:52,565 THAT MOST PEOPLE WHO SUCCUMB TO 429 00:19:52,565 --> 00:19:53,633 CONGENITAL HEART DISEASE ARE 15 430 00:19:53,633 --> 00:19:56,803 YEARS AND OLDER. 431 00:19:56,803 --> 00:19:59,005 AS A CONSEQUENCE OF THIS, THE 432 00:19:59,005 --> 00:20:02,708 MOST COMMON COHORT OF FOLKS WITH 433 00:20:02,708 --> 00:20:04,377 HEART DISEASE, THEY ARE ACTUALLY 434 00:20:04,377 --> 00:20:05,778 ADULTS AND NOT CHILDREN. 435 00:20:05,778 --> 00:20:10,817 SO DESPITE BEING LABELED HEART 436 00:20:10,817 --> 00:20:13,619 DISEASE, SO ABOUT 2.4 MILLION 437 00:20:13,619 --> 00:20:16,189 FOLKS ARE LIVING WITH CONGENITAL 438 00:20:16,189 --> 00:20:17,290 HEART DISEASE IN THE UNITED 439 00:20:17,290 --> 00:20:19,792 STATES TODAY, A MAJORITY ARE 440 00:20:19,792 --> 00:20:25,064 ADULTS, BECAUSE OF THE -- THERE 441 00:20:25,064 --> 00:20:28,101 HAS BEEN AN 85% INCREASED NUMBER 442 00:20:28,101 --> 00:20:29,402 OF ADULTS LIVING WITH SEVERE 443 00:20:29,402 --> 00:20:32,138 HEART DISEASE. 444 00:20:32,138 --> 00:20:34,207 BUT CONGENITAL HEART DISEASE HAS 445 00:20:34,207 --> 00:20:36,309 A HUGE IMPACT OP OUR MEDICAL 446 00:20:36,309 --> 00:20:41,514 ECONOMICS AND ACCOUNTS FOR -- AS 447 00:20:41,514 --> 00:20:45,384 WELL AS OVER $1.4 BILLION IN 448 00:20:45,384 --> 00:20:48,888 HOSPITAL COSTS. 449 00:20:48,888 --> 00:20:52,258 AS A REMINDER, THE HEART IS AN 450 00:20:52,258 --> 00:20:53,526 INTERTHORACIC ORGAN FOUND 451 00:20:53,526 --> 00:20:54,827 BETWEEN THE LUNGS AND SUPERIOR 452 00:20:54,827 --> 00:20:56,762 TO DIAPHRAGM AND MID THORAX. 453 00:20:56,762 --> 00:20:58,498 ALTHOUGH THE STRUCTURES OF THE 454 00:20:58,498 --> 00:21:00,900 HEART ARE PREDOMINANTLY IN THE 455 00:21:00,900 --> 00:21:05,605 LEFT HEMOTHORAX AS SHOWN IN THIS 456 00:21:05,605 --> 00:21:07,273 CT IMAGE. 457 00:21:07,273 --> 00:21:11,677 THE HEART WAYS ABOUT 250, 458 00:21:11,677 --> 00:21:12,445 350 GRAMS. 459 00:21:12,445 --> 00:21:14,147 ONE THING I LIKE TO POINT OUT TO 460 00:21:14,147 --> 00:21:15,381 MY CLINICAL TRAINEES IS THAT 461 00:21:15,381 --> 00:21:16,649 WHILE WE SORT OF IMAGINED THE 462 00:21:16,649 --> 00:21:19,485 HEART IS A VERTICAL ORGAN LIKE 463 00:21:19,485 --> 00:21:21,787 THE HALLMARK -- IT IN FACT A 464 00:21:21,787 --> 00:21:22,955 HORIZONTAL ORGAN BECAUSE ALL 465 00:21:22,955 --> 00:21:26,159 FOUR CHAMBERS OF THE HEART WILL 466 00:21:26,159 --> 00:21:30,563 GO TO -- ARE, IN FACT, ADJACENT 467 00:21:30,563 --> 00:21:33,065 TO THE INFERIORLY LOCATED 468 00:21:33,065 --> 00:21:33,599 DIAPHRAGM. 469 00:21:33,599 --> 00:21:35,701 THE THORACIC RELATIONSHIP IS 470 00:21:35,701 --> 00:21:37,436 IMPORTANT WITH REGARD TO 471 00:21:37,436 --> 00:21:40,239 PHYSICAL FINDINGS AND ARE OPEN 472 00:21:40,239 --> 00:21:42,808 FOR INTERPRETATION OF THE IMAGE 473 00:21:42,808 --> 00:21:43,476 ITSELF. 474 00:21:43,476 --> 00:21:44,744 IF ONE WERE TO GO AFTER YOU WITH 475 00:21:44,744 --> 00:21:48,214 AN ICE PICK, MOST ANTERIOR 476 00:21:48,214 --> 00:21:49,582 CHAMBER IS GOING TO BE THE RIGHT 477 00:21:49,582 --> 00:21:53,186 VENTRICLE, WHICH IS LOCATED HERE 478 00:21:53,186 --> 00:21:55,721 ON CT SCAN AS YOU CAN SEE THE 479 00:21:55,721 --> 00:21:59,192 LEFT ATRIUM AND WILL GO THROUGH 480 00:21:59,192 --> 00:22:01,127 THE SECOND IS THE MOST POSTERIOR 481 00:22:01,127 --> 00:22:01,594 ORGAN. 482 00:22:01,594 --> 00:22:10,269 THE APEX OF THE HEART IS IF WE 483 00:22:10,269 --> 00:22:14,407 ENTER -- THE -- BETWEEN THE 484 00:22:14,407 --> 00:22:16,976 BREAST BONE AND THE SHOULDER, 485 00:22:16,976 --> 00:22:19,212 THAT'S THE FIFTH INTERCOSTAL 486 00:22:19,212 --> 00:22:21,847 SPACE, WHERE YOU SEE YOUR POINT 487 00:22:21,847 --> 00:22:24,350 OF MAX MULL IMPULSE. 488 00:22:24,350 --> 00:22:26,352 THE HEART IS THE PUMP FOR THE 489 00:22:26,352 --> 00:22:28,254 CARDIOVASCULAR SYSTEM WHOSE 490 00:22:28,254 --> 00:22:31,157 PURPOSE IS TO TAKE NUTRIENTS TO 491 00:22:31,157 --> 00:22:33,759 THE BODY'S CELLS, WHILE REMOVING 492 00:22:33,759 --> 00:22:37,430 CARBON DIOXIDE GENERATED BY 493 00:22:37,430 --> 00:22:40,600 THE -- THE SYSTEM CONSISTS OF 494 00:22:40,600 --> 00:22:41,667 TWO SERIAL CIRCUITS AND THIS 495 00:22:41,667 --> 00:22:45,805 BECOMES IMPORTANT TO REMEMBER. 496 00:22:45,805 --> 00:22:47,873 SO RECEIVING OXYGEN-RICH BLOOD 497 00:22:47,873 --> 00:22:50,943 FROM THE LURNTION WITH AVERAGE 498 00:22:50,943 --> 00:22:53,012 HEMOGLOBIN SATURATION ABOUT 98% 499 00:22:53,012 --> 00:22:58,584 AND PEACIAL PRE PARTIAL PRESSURN 500 00:22:58,584 --> 00:23:00,019 THIS IS ARTERIAL BLOOD. 501 00:23:00,019 --> 00:23:01,454 THE BLOOD WILL ENTER THE LEFT 502 00:23:01,454 --> 00:23:02,521 VENTRICLE AND THEN IT'S 503 00:23:02,521 --> 00:23:04,724 DISTRIBUTED AT THE AORTA TO THE 504 00:23:04,724 --> 00:23:08,160 REST OF THE BODY THROUGH THE 505 00:23:08,160 --> 00:23:10,730 HEAD, ARMS AND DOWN TO THE 506 00:23:10,730 --> 00:23:12,398 INTESTINAL SYSTEM, KIDNEYS, AS 507 00:23:12,398 --> 00:23:18,070 WELL AS THE OTHER TISSUE. 508 00:23:18,070 --> 00:23:21,140 AFTER PASSING TO CAPILLARY BEDS, 509 00:23:21,140 --> 00:23:22,775 THE OXYGENATED OR BLUE BLOOD IS 510 00:23:22,775 --> 00:23:25,444 NOW RETURNED TO THE VENULES AND 511 00:23:25,444 --> 00:23:27,146 VEINS AND THE VENA CAVA, WHICH 512 00:23:27,146 --> 00:23:32,051 GOES TO THE RIGHT OF THE HEART, 513 00:23:32,051 --> 00:23:33,152 PUMPED -- TO BEGIN TO CYCLE 514 00:23:33,152 --> 00:23:33,919 AGAIN. 515 00:23:33,919 --> 00:23:37,523 THIS ENTIRE CYCLE TO TAKE A RED 516 00:23:37,523 --> 00:23:39,625 BLOOD CELL THROUGH THE ENTIRE 517 00:23:39,625 --> 00:23:46,732 CIRCUIT TAKES ABOUT 20 SECONDS. 518 00:23:46,732 --> 00:23:51,570 SO SI SIMPLE PHYSICS -- DRIVING 519 00:23:51,570 --> 00:23:52,438 FORWARD BLOOD THROUGH THE 520 00:23:52,438 --> 00:23:52,672 SYSTEM. 521 00:23:52,672 --> 00:23:54,807 SO IF WE START IN THE VENA CAVA 522 00:23:54,807 --> 00:23:57,009 HERE, WE SEE THAT OXYGEN 523 00:23:57,009 --> 00:24:00,513 SATURATION IS NOW DESATURATED 524 00:24:00,513 --> 00:24:01,947 BECAUSE OF THE OXYGEN EXCHANGE 525 00:24:01,947 --> 00:24:03,883 THAT'S OCCURRED, SATURATIONS ARE 526 00:24:03,883 --> 00:24:06,319 ABOUT 70% IN THE VENA CAVA, BOTH 527 00:24:06,319 --> 00:24:07,953 SUPERIOR AND INFERIOR, AND THE 528 00:24:07,953 --> 00:24:09,689 MEAN PRESSURES OF THIS PART OF 529 00:24:09,689 --> 00:24:11,891 THE SYSTEM, LESS THAN 530 00:24:11,891 --> 00:24:13,859 6 MILLIMETERS OF MERCURY. 531 00:24:13,859 --> 00:24:15,261 I'D LIKE YOU TO REMEMBER THAT 532 00:24:15,261 --> 00:24:16,696 NUMBER BECAUSE THIS IS GOING TO 533 00:24:16,696 --> 00:24:19,098 BECOME IMPORTANT AS WE TALK 534 00:24:19,098 --> 00:24:22,268 ABOUT OUR PROBLEM. 535 00:24:22,268 --> 00:24:25,871 THE RIGHT ATRIUM SATURATION 70%, 536 00:24:25,871 --> 00:24:28,841 MEAN PRESSURE IS LESS THAN 4. 537 00:24:28,841 --> 00:24:31,243 IT GOES FROM THE RIGHT ATRIUM TO 538 00:24:31,243 --> 00:24:32,878 THE TRICUSPID VALVE INTO THE 539 00:24:32,878 --> 00:24:34,847 RIGHT VENTRICLE, AND NOW BECAUSE 540 00:24:34,847 --> 00:24:38,384 OF THE PRESSURE THAT'S GENERATED 541 00:24:38,384 --> 00:24:40,419 BY THE CHAMBER FOR PEAK 542 00:24:40,419 --> 00:24:42,188 PRESSURE, SYSTOLIC PRESSURE IS 543 00:24:42,188 --> 00:24:43,389 ABOUT 25-MILLIMETERS OF MERCURY. 544 00:24:43,389 --> 00:24:45,224 ONCE IT GOES INTO THE PULMONARY 545 00:24:45,224 --> 00:24:47,326 ARTERY, IT'S ABOUT -- FROM THERE 546 00:24:47,326 --> 00:24:52,465 IT GOING TO ENTER THE -- SYSTEM, 547 00:24:52,465 --> 00:24:55,201 BECOME OXYGENATED, COME BACK 548 00:24:55,201 --> 00:24:56,936 AGAIN, LESS THAN 6 MILLIMETERS 549 00:24:56,936 --> 00:24:57,903 OF MERCURY. 550 00:24:57,903 --> 00:25:01,741 LEFT VENTRICLE GENERATES A 551 00:25:01,741 --> 00:25:03,843 PRESSURE AHEAD BETWEEN 120, 552 00:25:03,843 --> 00:25:07,847 130 MILLIMETERS OF MERCURY, INTO 553 00:25:07,847 --> 00:25:09,315 THE AORTA, WHERE IT'S THEN 554 00:25:09,315 --> 00:25:10,282 DISTRIBUTED TO THE REST OF THE 555 00:25:10,282 --> 00:25:19,258 BODY. 556 00:25:19,258 --> 00:25:21,560 THE ATRIA IS SHOWN IN YELLOW AND 557 00:25:21,560 --> 00:25:23,129 THE VENTRICLE IS SHOWN HERE IN 558 00:25:23,129 --> 00:25:27,566 THE BLUE. 559 00:25:27,566 --> 00:25:28,701 ONE CARDIAC CONTRACTION REFERRED 560 00:25:28,701 --> 00:25:30,836 TO AS THE SYSTOLE, THEN THE 561 00:25:30,836 --> 00:25:33,572 BLOOD IS PUMPED INTO THE AORTA, 562 00:25:33,572 --> 00:25:35,241 GENERATING A PRESSURE HEAD, THE 563 00:25:35,241 --> 00:25:35,775 AORTIC PRESSURE. 564 00:25:35,775 --> 00:25:42,114 THIS IS THE PRESSURE THAT WE SEE 565 00:25:42,114 --> 00:25:43,749 WHEN WE CHECK BLOOD PRESSURE BY 566 00:25:43,749 --> 00:25:45,284 A MANUAL CUFF. 567 00:25:45,284 --> 00:25:53,726 DURING DIASTOLE, THEY'LL FILL 568 00:25:53,726 --> 00:25:55,227 WITH BLOOD AND PUMP AGAIN. 569 00:25:55,227 --> 00:25:58,197 AS MENTIONED, OUR RED LINE HERE 570 00:25:58,197 --> 00:26:00,800 IS OUR AORTIC PRESSURE. 571 00:26:00,800 --> 00:26:03,335 IT'S BL 120 MILLIMETERS OF 572 00:26:03,335 --> 00:26:07,406 MERCURY. 573 00:26:07,406 --> 00:26:09,141 AND IS THE VENTRICLE PREPARED TO 574 00:26:09,141 --> 00:26:11,210 FILL BLOOD FROM THE ATRIUM, THE 575 00:26:11,210 --> 00:26:12,645 MEAN ATRIAL PRESSURES ARE LOW 576 00:26:12,645 --> 00:26:15,247 BUT NOT ZERO AND THIS IS 577 00:26:15,247 --> 00:26:17,016 REFERRED TO AS PRELOAD. 578 00:26:17,016 --> 00:26:19,852 NO WAY IN THE LEFT VENTRICLE, 579 00:26:19,852 --> 00:26:21,620 ATRIAL PRESSURE IS BELOW THE 580 00:26:21,620 --> 00:26:26,759 RANGE OF 55 LITERS OF MERCURY, 581 00:26:26,759 --> 00:26:27,726 HOWEVER -- ESPECIALLY WITH 582 00:26:27,726 --> 00:26:30,896 REGARDS TO RELAXATION, THESE 583 00:26:30,896 --> 00:26:31,997 HIGHER FILLING PRESSURES ARE 584 00:26:31,997 --> 00:26:34,400 REQUIRED. 585 00:26:34,400 --> 00:26:36,936 AS I MENTIONED A COUPLE TIMES, 586 00:26:36,936 --> 00:26:38,604 THIS IS GOING TO BE AN IMPORTANT 587 00:26:38,604 --> 00:26:39,538 CONCEPT THAT I'M GOING TO REFER 588 00:26:39,538 --> 00:26:46,879 TO LATER. 589 00:26:46,879 --> 00:26:49,148 SO THAT'S CARDIAC ANATOMY, 590 00:26:49,148 --> 00:26:56,822 NORMAL CARDIAC PHYSIOLOGY. 591 00:26:56,822 --> 00:27:02,895 NOW THAT WE'RE FAMILIAR WITH 592 00:27:02,895 --> 00:27:08,300 THIS, THIS IS THE AREA OF HEART 593 00:27:08,300 --> 00:27:11,570 DISEASE THAT ARE A CHALLENGING 594 00:27:11,570 --> 00:27:12,905 PROBLEM AND THAT'S THE ISSUE OF 595 00:27:12,905 --> 00:27:13,873 A SINGLE VENTRICLE. 596 00:27:13,873 --> 00:27:18,477 THERE'S A CLASSIC -- VENTRICLES 597 00:27:18,477 --> 00:27:21,747 ARE UNDERDEVELOPED, UNDERSIZED 598 00:27:21,747 --> 00:27:26,552 AND INADEQUATE CIRCULATION, IN 599 00:27:26,552 --> 00:27:33,459 FACT, IN SOME CASES, RATHER 600 00:27:33,459 --> 00:27:35,761 INVOKING A WHOLE LAUNDRY LIST, 601 00:27:35,761 --> 00:27:38,597 I'M GOING TO SIMPLY REFER TO ALL 602 00:27:38,597 --> 00:27:39,899 OF THESE AS SINGLE VENTRICLE. 603 00:27:39,899 --> 00:27:42,234 HERE IN THIS CASE, COMPARED TO 604 00:27:42,234 --> 00:27:46,805 OUR NORMAL DIAGRAM, THIS IS THE 605 00:27:46,805 --> 00:27:51,844 LEFT VENTRICLE, BECAUSE OF 606 00:27:51,844 --> 00:28:02,321 ATRESIA, THE NITRILE VALVE, 607 00:28:08,961 --> 00:28:13,699 THERE ARE SCORES OF VARIATION, 608 00:28:13,699 --> 00:28:18,871 EACH HAVE UNIQUE ETIOLOGY, AND 609 00:28:18,871 --> 00:28:24,209 EACH OF THEM HAVE ASSOCIATED 610 00:28:24,209 --> 00:28:29,682 CARDIAC DEFECT. 611 00:28:29,682 --> 00:28:33,719 BECAUSE BLOOD BEING A MIXTURE OF 612 00:28:33,719 --> 00:28:35,354 BOTH FULLY SATURATED AND 613 00:28:35,354 --> 00:28:36,455 DESATURATED BLOOD, THESE 614 00:28:36,455 --> 00:28:39,625 PATIENTS ARE OFTEN BLUE OR 615 00:28:39,625 --> 00:28:40,526 CYANOTIC. 616 00:28:40,526 --> 00:28:43,462 HOWEVER, FOR MANY OF THESE 617 00:28:43,462 --> 00:28:47,600 DEFECTS, THE MANAGEMENT GOAL IS 618 00:28:47,600 --> 00:28:50,669 A SYSTEM FOR FULLY RESTORED 619 00:28:50,669 --> 00:28:52,871 CIRCULATION TO IMPROVE 620 00:28:52,871 --> 00:28:58,010 OXYGENATION. 621 00:28:58,010 --> 00:28:59,778 I'M GOING TO GO BACK TO THIS AS 622 00:28:59,778 --> 00:29:02,181 A MODEL. 623 00:29:02,181 --> 00:29:04,350 SO THIS DEFECT IS CALLED 624 00:29:04,350 --> 00:29:05,017 HYPOPLASTIC LEFT HEART. 625 00:29:05,017 --> 00:29:07,519 WE'RE GOING TO USE THIS AS OUR 626 00:29:07,519 --> 00:29:11,690 ARCHETYPE BECAUSE THIS IS 627 00:29:11,690 --> 00:29:15,828 PROBABLY THE MOST COMMON SINGLE 628 00:29:15,828 --> 00:29:18,364 VENTRICLE ANATOMY THAT WE 629 00:29:18,364 --> 00:29:19,999 ENCOUNTER. 630 00:29:19,999 --> 00:29:24,603 IT OCCURS IN 1 IN 5,000 BIRTHS 631 00:29:24,603 --> 00:29:28,307 WITH ABOUT A THOUSAND BABIES 632 00:29:28,307 --> 00:29:30,809 BORN ANNUALLY WITH THIS 633 00:29:30,809 --> 00:29:32,511 CONDITION. 634 00:29:32,511 --> 00:29:35,047 PRIOR TO THIS, INFANTS WITH THIS 635 00:29:35,047 --> 00:29:36,281 DEFECT EXPERIENCED MORTALITY IN 636 00:29:36,281 --> 00:29:39,251 THE FIRST FEW WEEKS OR MONTHS OF 637 00:29:39,251 --> 00:29:41,654 LIFE. 638 00:29:41,654 --> 00:29:46,458 HYPOPLASTIC LEFT HEART, AORTIC 639 00:29:46,458 --> 00:29:49,194 VALVE, IS EITHER SEVERELY -- OR 640 00:29:49,194 --> 00:29:50,295 CYANOTIC. 641 00:29:50,295 --> 00:29:55,000 THE MITRAL VALVE TOO IS -- OR 642 00:29:55,000 --> 00:29:56,935 STENOTIC. 643 00:29:56,935 --> 00:30:07,479 THIS PREVIOUS CIRCLE -- THE LEFT 644 00:30:10,482 --> 00:30:11,617 VENTRICLE -- AND THE ONLY WAY 645 00:30:11,617 --> 00:30:15,020 THESE INFANTS REMAIN ALIVE IS 646 00:30:15,020 --> 00:30:17,189 BECAUSE OF THE PRESENCE OF THIS 647 00:30:17,189 --> 00:30:18,524 VESSEL HERE, AND THIS VESSEL IS 648 00:30:18,524 --> 00:30:21,794 REFERRED TO AS A PATENT DUCTUS 649 00:30:21,794 --> 00:30:30,235 DUCTUSARTERIOSUS OR PDA. 650 00:30:30,235 --> 00:30:31,370 THE PHYSIOLOGY AT BIRTH FOR 651 00:30:31,370 --> 00:30:33,505 THESE BABIES, BLUE BLOOD IS 652 00:30:33,505 --> 00:30:35,474 COMING BACK FROM THE HEAD AND 653 00:30:35,474 --> 00:30:37,342 THE LOWER BODY, SATURATION IS 654 00:30:37,342 --> 00:30:38,744 NORMALLY ABOUT 70% AND THESE 655 00:30:38,744 --> 00:30:43,682 CHILDREN, THE SATURATION SYSTEM 656 00:30:43,682 --> 00:30:48,921 IS MORE IN THE 60% RANGE. 657 00:30:48,921 --> 00:30:50,456 THE BLOOD FLOW BACK TO THE LUNGS 658 00:30:50,456 --> 00:30:53,525 IS FULLY SATURATED SO THIS IS 659 00:30:53,525 --> 00:30:56,361 98%, SO THE BLOOD IN THE RIGHT 660 00:30:56,361 --> 00:30:57,663 ATRIUM -- OR LEFT ATRIUM WOULD 661 00:30:57,663 --> 00:31:00,532 BE ABOUT 90%. 662 00:31:00,532 --> 00:31:02,367 BUT ALL THE BLOOD SINCE IT CAN'T 663 00:31:02,367 --> 00:31:04,770 EXIT THE LEFT ATRIUM THROUGH THE 664 00:31:04,770 --> 00:31:10,342 MICRO VALVES, IT HAS TO GO 665 00:31:10,342 --> 00:31:14,079 THROUGH A HOLE, LEFT OR RIGHT 666 00:31:14,079 --> 00:31:15,614 THROUGH THAT HOLE AND WE CREATE 667 00:31:15,614 --> 00:31:19,551 AN ADMIXTURE OF FLOW BETWEEN THE 668 00:31:19,551 --> 00:31:21,286 DESATURATED AND FULLY SATURATED 669 00:31:21,286 --> 00:31:21,854 BLOOD. 670 00:31:21,854 --> 00:31:24,123 SO THIS BLOOD TENDS TO RANGE IN 671 00:31:24,123 --> 00:31:27,092 A SATURATION OF 70%, SO IN OUR 672 00:31:27,092 --> 00:31:28,727 SUBSEQUENT DIAGRAMS, IF YOU SEE 673 00:31:28,727 --> 00:31:32,765 PPURPLE, THAT MEANS SATURATION 674 00:31:32,765 --> 00:31:33,532 ABOUT 70%. 675 00:31:33,532 --> 00:31:37,269 AND THESE PATIENTS WOULD BE 676 00:31:37,269 --> 00:31:40,205 VISIBLY CYANOTIC, IN AN INFANT 677 00:31:40,205 --> 00:31:44,910 OR AN ADULT NORPLY YO NORMALLY E 678 00:31:44,910 --> 00:31:47,646 SATURATIONS IN THE MID TO UPPER 679 00:31:47,646 --> 00:31:48,814 80s IF YOU'RE CYANOTIC. 680 00:31:48,814 --> 00:31:51,250 YOU CAN SEE ALL THE CARDIAC 681 00:31:51,250 --> 00:31:52,785 OUTPUT SINCE THE BLOOD CAN'T GO 682 00:31:52,785 --> 00:31:56,522 OUT THE AORTA, THIS IS NORMAL, 683 00:31:56,522 --> 00:31:57,656 THE BLOOD GOING TO THE HEAD, TO 684 00:31:57,656 --> 00:32:00,993 THE ARMS AND TO THE LOWER BODY 685 00:32:00,993 --> 00:32:03,629 IS GOING THROUGH THIS PATENT 686 00:32:03,629 --> 00:32:08,534 DUCTUS ARTERIOSUS. 687 00:32:08,534 --> 00:32:10,202 THE ISSUE, THOUGH, IS THAT PDA 688 00:32:10,202 --> 00:32:11,270 CLOSES. 689 00:32:11,270 --> 00:32:13,806 IN NORMAL PHYSIOLOGY, VARIOUS 690 00:32:13,806 --> 00:32:19,611 TRIGGERS, BIOCHEMICAL CHANGES, 691 00:32:19,611 --> 00:32:22,881 YOUR ACID BASE STATUS, IT 692 00:32:22,881 --> 00:32:23,982 PROMPTS PDA CLOSURE. 693 00:32:23,982 --> 00:32:26,385 SO THE PDA WILL ESSENTIALLY 694 00:32:26,385 --> 00:32:28,887 CLOSE EVEN THOUGH IT'S NEEDED TO 695 00:32:28,887 --> 00:32:32,591 MAINTAIN CIRCULATION. 696 00:32:32,591 --> 00:32:34,793 SO YOU CAN SEE ONCE THE PDA 697 00:32:34,793 --> 00:32:42,334 CLOSES THERE'S LESS CARDIAC 698 00:32:42,334 --> 00:32:43,335 OUTPUT, CARDIOVASCULAR CLEFT 699 00:32:43,335 --> 00:32:44,870 BECAUSE OF KNOW CARDIAC OUTPUT. 700 00:32:44,870 --> 00:32:47,039 SO THIS IS OUR ARCHETYPE MODEL, 701 00:32:47,039 --> 00:32:52,744 BUT I WANT TO GO BACK ONE STEP 702 00:32:52,744 --> 00:32:55,147 BECAUSE SURGEONS HAD TO FIGURE 703 00:32:55,147 --> 00:32:56,782 OUT THIS HAS TO BE TREATABLE BY 704 00:32:56,782 --> 00:32:57,983 MEDICATION OBVIOUSLY AND SOME 705 00:32:57,983 --> 00:32:59,384 TYPE OF INTERVENTION WOULD BE 706 00:32:59,384 --> 00:32:59,718 REQUIRED. 707 00:32:59,718 --> 00:33:01,153 AND THE PROBLEM OF THE SINGLE 708 00:33:01,153 --> 00:33:05,657 VENTRICLE AN ACTUALLY REALLY BEN 709 00:33:05,657 --> 00:33:09,695 IN THE LATE 60s. 710 00:33:09,695 --> 00:33:12,531 AT THE UNIVERSITY OF BORDEAUX, 711 00:33:12,531 --> 00:33:14,433 THE SURGEON WAS APPROACHED BY A 712 00:33:14,433 --> 00:33:15,567 COLLEAGUE ABOUT AN ADOLESCENT 713 00:33:15,567 --> 00:33:24,576 PATIENT WHO HAD A HEART DISEASE. 714 00:33:24,576 --> 00:33:25,344 WONDERING IF IT MIGHT BE 715 00:33:25,344 --> 00:33:27,512 POSSIBLE TO IMPROVE ON EXISTING 716 00:33:27,512 --> 00:33:30,082 SURGERY FOR CARDIAC 717 00:33:30,082 --> 00:33:32,117 MALFORMATION, FONTAN HAD DONE A 718 00:33:32,117 --> 00:33:38,223 SERIES OF EXPERIMENTS IN DOGS 719 00:33:38,223 --> 00:33:39,558 THROUGH THE PULMONARY ARTERY, 720 00:33:39,558 --> 00:33:43,829 WHICH IS HERE, ALLOWING BLOOD TO 721 00:33:43,829 --> 00:33:46,765 ENTER THE LUNGS. 722 00:33:46,765 --> 00:33:49,601 IT WAS INTERESTING, ALL THESE 723 00:33:49,601 --> 00:33:51,904 DOG SURGERIES WERE UNIFORMLY 724 00:33:51,904 --> 00:33:53,205 UNSUCCESSFUL. 725 00:33:53,205 --> 00:33:55,407 SO IT DOES SEEM A BIT SURPRISING 726 00:33:55,407 --> 00:33:58,911 THAT HIS COLLEAGUE WOULD HAVE 727 00:33:58,911 --> 00:34:01,513 APPROACHED DR. FONTAN ABOUT IT, 728 00:34:01,513 --> 00:34:03,282 BUT DR. FONTAN DID TAKE THIS 729 00:34:03,282 --> 00:34:09,521 WOMAN TO THE OPERATING ROOM AND 730 00:34:09,521 --> 00:34:11,256 DESPITE A ROCKY POSTOPERATIVE 731 00:34:11,256 --> 00:34:14,760 COURSE, THE WOMAN SURVIVED HIS 732 00:34:14,760 --> 00:34:17,829 SURGERY. 733 00:34:17,829 --> 00:34:21,233 SO IN TRICUSPID ATRESIA, THE TRY 734 00:34:21,233 --> 00:34:22,334 TRICUSPID VALVE, WHICH IS HERE, 735 00:34:22,334 --> 00:34:23,735 FAILS TO DEVELOP. 736 00:34:23,735 --> 00:34:26,905 AND WHEN IT FAILS TO DEVELOP, 737 00:34:26,905 --> 00:34:28,774 YOUR RIGHT VENTRICLE BECOMES 738 00:34:28,774 --> 00:34:33,912 HYPOPLASTIC. 739 00:34:33,912 --> 00:34:37,282 YOU CAN SEE OVERWEIGHT BLOOD IS 740 00:34:37,282 --> 00:34:40,886 ABLE TO GET OUT INTO THE LUNGS, 741 00:34:40,886 --> 00:34:42,354 ACTUALLY WOULD HAVE BEEN THROUGH 742 00:34:42,354 --> 00:34:44,189 RIGHT TO LEFT THROUGH THIS 743 00:34:44,189 --> 00:34:47,793 ATRIAL SEPTAL DEFECT, MIRING 744 00:34:47,793 --> 00:34:57,369 MIXING WITHTHE PULMONARY VENOUSG 745 00:34:57,369 --> 00:35:00,305 TOGETHER IN THE AORTA. 746 00:35:00,305 --> 00:35:02,174 WHAT FONTAN PROPOSED THAT WE'RE 747 00:35:02,174 --> 00:35:04,509 GOING TO CALL THE FONTAN -- 748 00:35:04,509 --> 00:35:05,677 WE'LL TALK ABOUT THAT IN ONE 749 00:35:05,677 --> 00:35:07,646 SECOND, HE PROPOSED CONNECTING A 750 00:35:07,646 --> 00:35:10,382 PORTION OF THE RIGHT ATRIUM 751 00:35:10,382 --> 00:35:11,917 CALLED THE APPENDAGE TO THE 752 00:35:11,917 --> 00:35:13,752 PULMONARY ARTERY ITSELF. 753 00:35:13,752 --> 00:35:17,055 AND BY DOING THAT, IT ALLOWS A 754 00:35:17,055 --> 00:35:19,558 CONNECTION FROM THE SYSTEMIC -- 755 00:35:19,558 --> 00:35:23,295 SIDE TO THE RIGHT ATRIUM TO THE 756 00:35:23,295 --> 00:35:26,565 APPENDAGE, THEREFORE PROVIDING A 757 00:35:26,565 --> 00:35:28,000 STABLE SUPPLY OF BLOOD FLOW. 758 00:35:28,000 --> 00:35:31,937 THE BLOOD COMING FROM THE 759 00:35:31,937 --> 00:35:34,006 PULMONARY VEIN WAS NOW FULLY 760 00:35:34,006 --> 00:35:35,207 SATURATE AND THERE WAS NO 761 00:35:35,207 --> 00:35:36,608 ADMIXTURE BETWEEN THE TWO. 762 00:35:36,608 --> 00:35:41,213 THIS SURGERY SUCCESSFULLY 763 00:35:41,213 --> 00:35:42,414 SEPARATES -- CARDIAC OUTPUT 764 00:35:42,414 --> 00:35:43,615 RECOVERED AND THIS PATIENT'S 765 00:35:43,615 --> 00:35:45,050 CYANOSIS WAS RESOLVED. 766 00:35:45,050 --> 00:35:47,986 AND AS I MENTIONED, DESPITE A 767 00:35:47,986 --> 00:35:52,624 RATHER ROCKY -- HE DID SURVIVE 768 00:35:52,624 --> 00:35:53,692 AND RECOVERED. 769 00:35:53,692 --> 00:36:00,132 SO DR. FONTAN -- 32 PATIENTS IN 770 00:36:00,132 --> 00:36:06,605 1971, ARGENTINA -- SURGICAL 771 00:36:06,605 --> 00:36:07,773 APPROACH -- THEY'RE BOTH HONORED 772 00:36:07,773 --> 00:36:09,641 TODAY BY NAMING THIS PROCEDURE 773 00:36:09,641 --> 00:36:12,978 THE FONTAN KREUTZER PROCEDURE 774 00:36:12,978 --> 00:36:14,913 BUT FOR SIMPLICITY TO AVOID ME 775 00:36:14,913 --> 00:36:16,348 CONSTANTLY TRIPPING OVER THIS, 776 00:36:16,348 --> 00:36:17,649 I'M SIMPLY GOING TO REMEMBER TO 777 00:36:17,649 --> 00:36:23,889 THIS AS THE FONTAN PROCEDURE. 778 00:36:23,889 --> 00:36:25,857 SO THE SINGLE VENTRICLE 779 00:36:25,857 --> 00:36:28,927 HYPOPLASTIC LEFT HEART. 780 00:36:28,927 --> 00:36:33,832 UNLIKE THE -- IT IS THE SYSTEMIC 781 00:36:33,832 --> 00:36:35,901 LEFT VENTRICLE THAT IS 782 00:36:35,901 --> 00:36:38,870 UNDERDEVELOPED AND THE OTHER 783 00:36:38,870 --> 00:36:39,805 CRITICAL ISSUES WE TALK ABOUT 784 00:36:39,805 --> 00:36:41,706 THE FACT THAT ALL THE CARDIAC 785 00:36:41,706 --> 00:36:43,141 OUTPUT WAS GOING TO THE PDA 786 00:36:43,141 --> 00:36:45,310 WHICH WAS DESTINED TO CLOSE. 787 00:36:45,310 --> 00:36:53,852 SEE MY ARROW HERE, REMEMBER TH 788 00:36:53,852 --> 00:36:56,021 THE -- AND OUR PATENT DUCTUS 789 00:36:56,021 --> 00:36:56,321 ARTERIOSUS. 790 00:36:56,321 --> 00:37:00,292 SO THE NEXT SERIES OF DIAGRAMS 791 00:37:00,292 --> 00:37:03,462 SHOWS SOME OF THE COMPLEXITY 792 00:37:03,462 --> 00:37:07,632 OF -- AND SERIOUS SURGERY THAT 793 00:37:07,632 --> 00:37:08,934 IT TAKES -- I DON'T WANT TO GET 794 00:37:08,934 --> 00:37:10,802 TOO MUCH INTO THE WEEDS BUT 795 00:37:10,802 --> 00:37:12,771 WE'RE GOING TO BE TALKING ABOUT 796 00:37:12,771 --> 00:37:17,375 A THREE-STAGE PROCEDURE TO 797 00:37:17,375 --> 00:37:18,677 PALLIATE THIS COMPLEX HEART 798 00:37:18,677 --> 00:37:19,010 DISEASE. 799 00:37:19,010 --> 00:37:21,313 SO AS WE TALKED ABOUT AT BIRTH, 800 00:37:21,313 --> 00:37:24,583 THIS IS WHAT OUR CHILD LOOKS 801 00:37:24,583 --> 00:37:25,250 LIKE. 802 00:37:25,250 --> 00:37:27,185 SO THE FIRST THING WE HAD TO DO 803 00:37:27,185 --> 00:37:31,022 WAS TO CREATE A -- AORTA, WHICH 804 00:37:31,022 --> 00:37:33,658 IS RIGHT HERE, SO AGAIN, IF YOU 805 00:37:33,658 --> 00:37:35,293 LOOK HERE, WE HAD TO GET RID OF 806 00:37:35,293 --> 00:37:37,262 THIS PDA, WE HAD TO GET BLOOD 807 00:37:37,262 --> 00:37:39,464 INTO THE AORTA ITSELF AND SO YOU 808 00:37:39,464 --> 00:37:47,672 DO THIS BY CREATING A CONNECTION 809 00:37:47,672 --> 00:37:49,207 FROM THE ASCENDING AORTA 810 00:37:49,207 --> 00:37:51,243 BASICALLY USING THE PULMONARY 811 00:37:51,243 --> 00:37:53,178 ARTERY TO CREATE A NEW PULMONARY 812 00:37:53,178 --> 00:37:54,312 ARTERY. 813 00:37:54,312 --> 00:37:56,414 THIS PROVIDES RELIABLE SOURCE OF 814 00:37:56,414 --> 00:37:56,848 BLOOD FLOW. 815 00:37:56,848 --> 00:37:59,684 WE ADDED A SHUNT SHOWING HERE, 816 00:37:59,684 --> 00:38:01,786 WHICH NOW PROVIDES RELIABLE 817 00:38:01,786 --> 00:38:06,491 PULMONARY BLOOD FLOW. 818 00:38:06,491 --> 00:38:07,659 WE CREATE THIS BECAUSE WE DON'T 819 00:38:07,659 --> 00:38:10,529 WANT ANYTHING TO OBSTRUCT FLOW 820 00:38:10,529 --> 00:38:12,164 AND RETURN OF THE VENOUS BLOOD, 821 00:38:12,164 --> 00:38:16,201 SO NOW WHAT WE SEE IS OUR VENA 822 00:38:16,201 --> 00:38:19,838 CAVAL FLOW GOING INTO THE RIGHT 823 00:38:19,838 --> 00:38:23,542 ATRIUM, VENOUS RETURN TO RIGHT 824 00:38:23,542 --> 00:38:26,478 ATRIUM, MIXING GOING INTO THE 825 00:38:26,478 --> 00:38:29,447 AORTA WHO IS NOW BLUE, WE HAVE 826 00:38:29,447 --> 00:38:34,786 STABLE CARDIAC OUTPUT AS WELL AS 827 00:38:34,786 --> 00:38:36,121 VENOUS FLOW THROUGH OUR SHUNT. 828 00:38:36,121 --> 00:38:37,522 THIS WAS DONE WITHIN A COUPLE 829 00:38:37,522 --> 00:38:40,592 DAYS OF BIRTH. 830 00:38:40,592 --> 00:38:42,994 THE NEXT, THIS IS A PROCEDURE TO 831 00:38:42,994 --> 00:38:45,463 BASICALLY ALLOW VOLUME UNLOADING 832 00:38:45,463 --> 00:38:46,965 OF THE HEART. 833 00:38:46,965 --> 00:38:50,969 SO WE NOW CREATE ANASTOMOSIS 834 00:38:50,969 --> 00:38:53,071 BETWEEN THE SUPERIOR VENA CAVA 835 00:38:53,071 --> 00:38:54,806 AND PULMONARY ARTERY THAT WE 836 00:38:54,806 --> 00:38:58,310 CALL A MODIFIED GLENN OR 837 00:38:58,310 --> 00:38:58,710 HEMI-FONTAN. 838 00:38:58,710 --> 00:39:02,581 THAT SHUNT W WE HAD HERE, WE TOK 839 00:39:02,581 --> 00:39:04,449 THAT DOWN SO NOW YOU CAN SEE WE 840 00:39:04,449 --> 00:39:08,153 HAVE A STABLE BLOOD FLOW, IVC IS 841 00:39:08,153 --> 00:39:10,222 MIXING STILL WITH THE PULMONARY 842 00:39:10,222 --> 00:39:12,857 VENOUS RETURN, AND IT'S STILL 843 00:39:12,857 --> 00:39:15,060 BLUE, BUT NOW WE STILL HAVE A 844 00:39:15,060 --> 00:39:16,695 STABLE BLOOD FLOW. 845 00:39:16,695 --> 00:39:19,531 AGAIN, AS I MENTIONED, THIS 846 00:39:19,531 --> 00:39:22,167 ALLOWS UNLOADING AT A DISTANT 847 00:39:22,167 --> 00:39:23,902 VENTRICLE SO THE PATIENT REMAINS 848 00:39:23,902 --> 00:39:24,569 CYANOTIC. 849 00:39:24,569 --> 00:39:26,204 FINALLY THE FONTAN, WHICH IS A 850 00:39:26,204 --> 00:39:29,140 STAGE III, WHICH IS OUR TOTAL 851 00:39:29,140 --> 00:39:31,910 ANASTOMOSIS, WHAT WE'RE DOING 852 00:39:31,910 --> 00:39:34,946 HERE IS WE'RE ADDING IN A 853 00:39:34,946 --> 00:39:36,715 TUNNEL, A PATCH OR WE CAN PUT A 854 00:39:36,715 --> 00:39:40,118 TUBE GRAFT IN THAT'S GOING TO 855 00:39:40,118 --> 00:39:42,621 DIRECT FLOAM TO THE PULMONARY 856 00:39:42,621 --> 00:39:44,789 ARTERY AND SEV HAS ALREADY BEEN 857 00:39:44,789 --> 00:39:45,290 CONNECTED. 858 00:39:45,290 --> 00:39:47,325 SO YOU CAN SEE NOW OUR BLOOD HAS 859 00:39:47,325 --> 00:39:48,727 M COME BACK THROUGH THE LEFT 860 00:39:48,727 --> 00:39:50,996 ATRIUM IS COMPLETELY SEPARATED 861 00:39:50,996 --> 00:39:55,467 FROM THE SYSTEMIC VENOUS RETURN 862 00:39:55,467 --> 00:39:56,735 SO THE PATIENT IS FULLY 863 00:39:56,735 --> 00:39:58,470 SATURATED. 864 00:39:58,470 --> 00:40:07,012 AS WE FIND -- THE SCOPE OF THIS 865 00:40:07,012 --> 00:40:08,013 DISCUSSION RIGHT NOW. 866 00:40:08,013 --> 00:40:09,114 CURRENTLY THERE'S THREE 867 00:40:09,114 --> 00:40:11,616 VARIATIONS OF FONTAN. 868 00:40:11,616 --> 00:40:12,951 THERE'S ORIGINAL AORTIC 869 00:40:12,951 --> 00:40:15,353 PULMONARY SECTION AND DR. FONTAN 870 00:40:15,353 --> 00:40:16,021 HAD DESCRIBED. 871 00:40:16,021 --> 00:40:18,089 YOU CAN PUT A PATCH IN HERE TO 872 00:40:18,089 --> 00:40:20,492 DIRECT FLOW FROM THE IVC UP INTO 873 00:40:20,492 --> 00:40:23,795 THE S DC PULMONARY ARTERY, 874 00:40:23,795 --> 00:40:34,439 CALLED THE LATERAL - -- WHEN YOU 875 00:40:35,206 --> 00:40:38,543 LOOK AT -- AS WE'RE TRYING TO 876 00:40:38,543 --> 00:40:39,944 DEFINE EXACTLY WHAT IS AN 877 00:40:39,944 --> 00:40:42,247 OPTIMAL APPROACH, I'LL SHARE 878 00:40:42,247 --> 00:40:46,951 SOME DATA HERE IN JUST A LITTLE 879 00:40:46,951 --> 00:40:48,920 BIT, COMPUTATIONAL FLUID 880 00:40:48,920 --> 00:40:51,990 DYNAMICS CONDUCTED BY CARDIAC 881 00:40:51,990 --> 00:40:55,927 MI, THIS IS PROBABLY THE MOST 882 00:40:55,927 --> 00:40:58,196 OPTIMAL APPROACH BECAUSE ARE IT 883 00:40:58,196 --> 00:41:01,933 MINIMIZES POWER LOSS OF FLOW, 884 00:41:01,933 --> 00:41:02,801 AND ONE OF THE CHALLENGES WITH 885 00:41:02,801 --> 00:41:07,939 THIS TYPE OF CIRCUIT IS -- SO 886 00:41:07,939 --> 00:41:10,041 BECAUSE THERE'S LESS COMPETITION 887 00:41:10,041 --> 00:41:12,644 BETWEEN THE SCV AND IVC FLOW 888 00:41:12,644 --> 00:41:18,550 COMING IN TO THE PULMONARY 889 00:41:18,550 --> 00:41:21,386 ARTERY, [INAUDIBLE] OTHER 890 00:41:21,386 --> 00:41:22,921 ADVANTAGES AS WELL. 891 00:41:22,921 --> 00:41:27,325 AS FAR AS INDICATIONS FOR THE 892 00:41:27,325 --> 00:41:35,166 FONTAN, AGAIN, THE HYPOPLAS 893 00:41:35,166 --> 00:41:36,167 HYPOPLASTIC -- TRICUSPID 894 00:41:36,167 --> 00:41:36,935 ATRESIA. 895 00:41:36,935 --> 00:41:40,538 WE TALKED BRIEFLY ABOUT THE 896 00:41:40,538 --> 00:41:42,507 ETIOLOGY FOR THE SINGLE 897 00:41:42,507 --> 00:41:42,941 VENTRICLE. 898 00:41:42,941 --> 00:41:44,376 IN A NORMAL SITUATION, WE HAVE A 899 00:41:44,376 --> 00:41:48,113 LEFT VENTRICLE, WE HAVE A RIGHT 900 00:41:48,113 --> 00:41:49,748 VENTRICLE, AND -- CONNECTS TO 901 00:41:49,748 --> 00:41:52,050 THE PULMONARY CIRCULATION IN 902 00:41:52,050 --> 00:41:53,118 THEORY. 903 00:41:53,118 --> 00:41:54,886 THE MOST IMPORTANT TAKEAWAY FROM 904 00:41:54,886 --> 00:41:56,855 THIS, AGAIN, THIS IS OUR CHANGE 905 00:41:56,855 --> 00:41:59,023 IN PRESSURE OVER TIME CURVE, 906 00:41:59,023 --> 00:42:03,962 LEFT VENTRICLE, AS IT GOES 907 00:42:03,962 --> 00:42:06,364 THROUGH THE MAJOR ARTERIES, 908 00:42:06,364 --> 00:42:09,768 ARTERIOLES AND CAPILLARY BED 909 00:42:09,768 --> 00:42:12,504 REPRESENTED HERE, SYSTEMIC 910 00:42:12,504 --> 00:42:13,471 VENOUS RETURN THROUGH HERE, INTO 911 00:42:13,471 --> 00:42:15,774 THE RIGHT ATRIUM, RIGHT 912 00:42:15,774 --> 00:42:17,409 VENTRICLE, RIGHT VENTRICLE THEN 913 00:42:17,409 --> 00:42:20,979 INCREASES PRESSURE AND GETS IN 914 00:42:20,979 --> 00:42:22,113 THE PULMONARY CIRCUIT AND THEN 915 00:42:22,113 --> 00:42:27,819 WE START THE CYCLE OVER AGAIN. 916 00:42:27,819 --> 00:42:29,654 THE MOST IMPORTANT THING I WANT 917 00:42:29,654 --> 00:42:30,855 TO POINT OUT IS THE DRIVING 918 00:42:30,855 --> 00:42:34,359 FORCE TO OVERCOME -- NOW IN A 919 00:42:34,359 --> 00:42:36,694 FONTAN, WE HAVE BLOOD THAT'S 920 00:42:36,694 --> 00:42:39,297 GOING THROUGH THE SYSTEM. 921 00:42:39,297 --> 00:42:43,768 THIS VENTRICLE HAS TO -- LIKE 922 00:42:43,768 --> 00:42:45,203 THIS NORMAL CIRCULATION WHERE WE 923 00:42:45,203 --> 00:42:46,171 HAVE TWO VENTRICLES ABLE TO 924 00:42:46,171 --> 00:42:47,238 PROVIDE THE TOTAL ENERGY IN 925 00:42:47,238 --> 00:42:49,574 ORDER TO GET BLOOD TO THE LUNGS 926 00:42:49,574 --> 00:42:51,676 AND OUR FONTAN, WE HAVE ONLY A 927 00:42:51,676 --> 00:42:55,713 SINGLE VENTRICLE THAT COULD -- 928 00:42:55,713 --> 00:42:57,982 THAT INITIAL PRESSURE GRADIENT, 929 00:42:57,982 --> 00:43:02,687 AND ONCE WE GET TO THE -- IT A 930 00:43:02,687 --> 00:43:04,456 CENTRAL BETA PRESSURE, NOT A 931 00:43:04,456 --> 00:43:13,398 VENTRICLE THAT'S PROVIDING -- 932 00:43:13,398 --> 00:43:16,301 WHAT HAPPEN PS OVER TIME, 933 00:43:16,301 --> 00:43:18,603 PULMONARY VASCULAR DISTANCE HERE 934 00:43:18,603 --> 00:43:21,739 INCREASES, AND AS THAT 935 00:43:21,739 --> 00:43:24,476 INCREASES, THE CENTRAL VENOUS 936 00:43:24,476 --> 00:43:25,477 PRESSURE MUST INCREASE TO 937 00:43:25,477 --> 00:43:26,778 MAINTAIN CARDIAC OUTPUT, AND TO 938 00:43:26,778 --> 00:43:31,382 THINK WHEN YOU INCREASE -- THAT 939 00:43:31,382 --> 00:43:34,219 INCLUDES THE SYSTEM -- AND THERE 940 00:43:34,219 --> 00:43:39,691 ARE CLINICAL SIGNS AND SYMPTOMS. 941 00:43:39,691 --> 00:43:41,459 AND AS TIME GOES ON, AND WE'LL 942 00:43:41,459 --> 00:43:43,862 TALK A LITTLE BIT AGAIN, WE SEE 943 00:43:43,862 --> 00:43:48,766 THAT THE CARDIAC OUTPUT 944 00:43:48,766 --> 00:43:50,635 DECREASES RELATED TO RISK 945 00:43:50,635 --> 00:43:51,402 FACTORS. 946 00:43:51,402 --> 00:43:53,371 MORBIDITY AND COMPLICATION ARE 947 00:43:53,371 --> 00:43:55,006 DIRECTLY ASSOCIATED TO BOTH 948 00:43:55,006 --> 00:43:56,975 INCREASE IN CDC AND CARDIAC 949 00:43:56,975 --> 00:43:58,409 OUTPUT. 950 00:43:58,409 --> 00:44:00,578 ONE MEASURE OF CARDIAC OUTPUT IS 951 00:44:00,578 --> 00:44:06,718 EJECTION FRACTION, OR EF HERE. 952 00:44:06,718 --> 00:44:10,221 WHICH IS PERCENTAGE OF VOLUME 953 00:44:10,221 --> 00:44:11,122 INJECTED INTO THE -- 954 00:44:11,122 --> 00:44:11,689 CONTRACTIONS. 955 00:44:11,689 --> 00:44:17,662 THE NORMAL EF, WHICH IS HERE, 956 00:44:17,662 --> 00:44:19,097 NORMAL EF, NORMAL HEART, 957 00:44:19,097 --> 00:44:21,099 EJECTION FRACTION IS BETWEEN 55 958 00:44:21,099 --> 00:44:22,800 AND 70%. 959 00:44:22,800 --> 00:44:26,538 IN A WELL FUNCTIONING FONTAN, 960 00:44:26,538 --> 00:44:29,274 EVEN THE PRESENCE OF THAT, WE 961 00:44:29,274 --> 00:44:31,209 FIND OUR CARDIAC OUTPUT IS GOING 962 00:44:31,209 --> 00:44:36,047 TO BE MUCH LOWER, EVEN THOUGH 963 00:44:36,047 --> 00:44:39,751 ESSENTIAL FACTOR IS -- AS YOUR 964 00:44:39,751 --> 00:44:44,022 EF DIMINISHES IN A FONTAN, YOU 965 00:44:44,022 --> 00:44:46,057 CAN SEE OUR CARDIAC DECREASES, 966 00:44:46,057 --> 00:44:47,625 AND YOU CAN SEE HOW HIGHLY 967 00:44:47,625 --> 00:44:50,595 DEPENDENT IT IS ON -- SO THEIR 968 00:44:50,595 --> 00:45:01,105 PVR INCREASES, EF -- INCREASED 969 00:45:03,074 --> 00:45:05,043 NUMBER OF ADULT PATIENTS NOW 970 00:45:05,043 --> 00:45:08,313 LIVEING WITH THE FONTAN IS NOW 971 00:45:08,313 --> 00:45:11,049 ESTIMATED AT ABOUT 40% OF 972 00:45:11,049 --> 00:45:13,117 PATIENTS THAT HAVE A FONTAN ARE 973 00:45:13,117 --> 00:45:15,753 OVER 18 YEARS OF AGE. 974 00:45:15,753 --> 00:45:20,258 THIS GRAPH SHOWS THE LONG-TERM 975 00:45:20,258 --> 00:45:28,666 SURVIVAL, AND OVERALL ESTIMATED 976 00:45:28,666 --> 00:45:30,001 SURVIVAL -- SO ESTIMATED 977 00:45:30,001 --> 00:45:32,303 SURVIVAL, 30-YEAR SURVIVAL FOR 978 00:45:32,303 --> 00:45:34,672 THE PATIENT WITH A FONTAN IS 979 00:45:34,672 --> 00:45:36,040 ABOUT 85%. 980 00:45:36,040 --> 00:45:37,375 WE TALK ABOUT THREE DIFFERENT 981 00:45:37,375 --> 00:45:38,443 TYPES OF FONTANS. 982 00:45:38,443 --> 00:45:41,512 WE TALK ABOUT THE EXTRA CARDIAC 983 00:45:41,512 --> 00:45:44,349 CONTENT, THAT TUBE GRAFT, 984 00:45:44,349 --> 00:45:45,683 REPRESENTED BY THIS SOLID BAR 985 00:45:45,683 --> 00:45:47,085 HERE, THE LATERAL TUNNEL, WHICH 986 00:45:47,085 --> 00:45:50,688 IS THAT PATCH WE PUT IN, AND THE 987 00:45:50,688 --> 00:45:52,056 PULMONARY CONNECTION, THE ONE 988 00:45:52,056 --> 00:45:56,060 THAT DR. FAN ORIGINALLY 989 00:45:56,060 --> 00:45:57,929 CONCEIVED. 990 00:45:57,929 --> 00:46:00,665 NOW, IF YOU LOOK AT PATIENTS WHO 991 00:46:00,665 --> 00:46:04,268 HAVE INTACT FONTAN CIRCULATION, 992 00:46:04,268 --> 00:46:07,338 THAT PREVIOUS WAS ABOUT OVERALL 993 00:46:07,338 --> 00:46:08,439 SURVIVAL BUT PATIENTS CAN 994 00:46:08,439 --> 00:46:11,576 REQUIRE CONTINUED INTERVENTION. 995 00:46:11,576 --> 00:46:16,080 SO AT 20 YEARS OF AGE, 74% ARE 996 00:46:16,080 --> 00:46:17,048 INTERVENTION-FREE, 8% OF THEM 997 00:46:17,048 --> 00:46:21,119 WILL HAVE HAD A TRANSPLANT AT -- 998 00:46:21,119 --> 00:46:26,357 OR 20 YEARS -- AND SOME HAD IT 999 00:46:26,357 --> 00:46:27,025 TAKEN DOWN. 1000 00:46:27,025 --> 00:46:32,830 WHEN WE TALK ABOUT -- PRESERVE 1001 00:46:32,830 --> 00:46:37,335 EJECTION FRACTION OR REDUCE THE 1002 00:46:37,335 --> 00:46:38,636 EJECTION FRACTION. 1003 00:46:38,636 --> 00:46:40,838 YOU SEE BOTH HYPERTROPHY AND 1004 00:46:40,838 --> 00:46:41,272 DILATION. 1005 00:46:41,272 --> 00:46:49,147 ALSO WE SEE AN INCREASE IN THE 1006 00:46:49,147 --> 00:46:51,249 INABILITY TO RELAX. 1007 00:46:51,249 --> 00:46:52,550 CORONARY INSUFFICIENCY IS 1008 00:46:52,550 --> 00:46:57,121 COMMON, AND NOW WE HAVE INSTEAD 1009 00:46:57,121 --> 00:47:03,795 OF -- WE HAVE TWO AV VALVES. 1010 00:47:03,795 --> 00:47:05,663 IN OUR SINGLE VENTRICLE 1011 00:47:05,663 --> 00:47:16,174 PATIENTS, WE HAVE ONE, -- BOTH 1012 00:47:18,976 --> 00:47:19,877 CONGENITAL ANATOMY, BECAUSE OF 1013 00:47:19,877 --> 00:47:21,746 SURGICAL SCARRING, THESE ARE 1014 00:47:21,746 --> 00:47:26,984 COMMON IN FONTAN CASES. 1015 00:47:26,984 --> 00:47:29,420 EACH ANATOMIC SUBSTRATE IS 1016 00:47:29,420 --> 00:47:32,156 SINGLE VENTRICLE, EACH POSES ITS 1017 00:47:32,156 --> 00:47:33,691 OWN CHALLENGE. 1018 00:47:33,691 --> 00:47:35,660 NOW THE SUTURE LINES THAT GO 1019 00:47:35,660 --> 00:47:38,296 THROUGH THE SURGERY INTERFERE 1020 00:47:38,296 --> 00:47:41,132 WITH ATRIAL CONDUCTION. 1021 00:47:41,132 --> 00:47:45,503 IT MAY ACTUALLY HAVE A LOWER -- 1022 00:47:45,503 --> 00:47:47,371 THAT'S ANOTHER REASON IT'S 1023 00:47:47,371 --> 00:47:51,743 BECOME THE MORE FAVORED 1024 00:47:51,743 --> 00:47:52,276 TECHNIQUE. 1025 00:47:52,276 --> 00:47:54,479 10 YEARS AFTER A FONTAN, 15% OF 1026 00:47:54,479 --> 00:48:01,152 PATIENTS WILL HAVE SOME TYPE O 1027 00:48:01,152 --> 00:48:12,196 OF -- EITHER BRAY EE RIT -- YOU0 1028 00:48:23,207 --> 00:48:28,513 YEARS -- 15 YEARS. 1029 00:48:28,513 --> 00:48:29,147 COMORBIDITIES ARE COMMON. 1030 00:48:29,147 --> 00:48:31,482 ONE OF THE THINGS THAT WE'RE 1031 00:48:31,482 --> 00:48:33,217 RECOGNIZING IS LIKE THE LONGER 1032 00:48:33,217 --> 00:48:36,821 PATIENTS ARE SURVIVING, ONCE 1033 00:48:36,821 --> 00:48:39,223 THEY HAVE INCURRED -- SURVIVED 1034 00:48:39,223 --> 00:48:42,927 THE INITIAL SURGERY, 10, 15, 20, 1035 00:48:42,927 --> 00:48:44,462 25 YEARS AFTER THE SURGERY, 1036 00:48:44,462 --> 00:48:46,264 WE'RE STARTING TO IDENTIFY OTHER 1037 00:48:46,264 --> 00:48:49,000 PROBLEMS. 1038 00:48:49,000 --> 00:48:50,201 LYMPHATIC DYSFUNCTION IS NOT 1039 00:48:50,201 --> 00:48:55,339 UNCOMMON AND PROBABLY LED TO 1040 00:48:55,339 --> 00:49:03,080 PRESSURE ELEVATION AS WELL AS -- 1041 00:49:03,080 --> 00:49:07,018 PRPRO-INFLAMMATORY STATE ALTERIG 1042 00:49:07,018 --> 00:49:08,920 MEMBRANE PERMEABILITY, AS WELL 1043 00:49:08,920 --> 00:49:12,056 AS VARIABILITY IN LYMPHATIC 1044 00:49:12,056 --> 00:49:14,392 SYSTEM WHICH MAY DISPOSE TO 1045 00:49:14,392 --> 00:49:16,460 COMORBIDITIES. 1046 00:49:16,460 --> 00:49:27,004 IN MORE DETAIL THAT HAS BEEN 1047 00:49:31,509 --> 00:49:33,177 BEEN -- -- WHICH AFFECTS 5 TO 1048 00:49:33,177 --> 00:49:36,047 12% OF PATIENTS WITH FONTAN 1049 00:49:36,047 --> 00:49:39,884 CIRCULATION, AND ALSO CLASSIC 1050 00:49:39,884 --> 00:49:41,419 BRONCHITIS, THICK TENACIOUS 1051 00:49:41,419 --> 00:49:44,355 CASTS WITHIN THE AIRWAY LUMEN. 1052 00:49:44,355 --> 00:49:51,929 THIS OCCURS IN A SMALL NUMBER OF 1053 00:49:51,929 --> 00:49:58,035 PATIENTS WITH FONTAN. 1054 00:49:58,035 --> 00:50:01,806 -- A QUICK SHOUT OUT TO 1055 00:50:01,806 --> 00:50:02,206 DR. HELLER. 1056 00:50:02,206 --> 00:50:06,277 BEFORE WE DO, I'D LIKE TO 1057 00:50:06,277 --> 00:50:15,453 INTRODUCE A PATIENT, BUT BEFO 1058 00:50:15,453 --> 00:50:16,554 BEFORE -- SO WE'VE KNOWN EACH 1059 00:50:16,554 --> 00:50:20,391 OTHER BEFORE SHE WAS BORN, AND 1060 00:50:20,391 --> 00:50:21,926 AS IT TURNS OUT, I FOLLOWED HER 1061 00:50:21,926 --> 00:50:27,398 FOR CLOSE TO 20 YEARS, AND AS I 1062 00:50:27,398 --> 00:50:28,399 TRANSITIONED OUT OF MILITARY, 1063 00:50:28,399 --> 00:50:30,601 SHE TRANSITIONED AS WELL AND 1064 00:50:30,601 --> 00:50:34,872 BEING FOLLOWED BY DR. HELLER -- 1065 00:50:34,872 --> 00:50:35,640 FONTAN PROTOCOL. 1066 00:50:35,640 --> 00:50:37,909 SO THIS IS ANGELICA'S HEART. 1067 00:50:37,909 --> 00:50:41,445 SHE WAS BORN WITH TRICUSPID 1068 00:50:41,445 --> 00:50:42,847 ATRESIA. 1069 00:50:42,847 --> 00:50:47,451 SHE HAD -- THE AORTA -- HAVE 1070 00:50:47,451 --> 00:50:50,187 ACTUALLY SWITCHED IN PLACE. 1071 00:50:50,187 --> 00:50:53,124 SO NORMALLY THE RIGHT VENTRICLE, 1072 00:50:53,124 --> 00:50:54,358 YOU PUMP BLOOD INTO THE 1073 00:50:54,358 --> 00:50:54,792 PULMONARY ARTERY. 1074 00:50:54,792 --> 00:50:57,862 HERE IN HER ANATOMY, HERS WAS 1075 00:50:57,862 --> 00:50:59,196 PUMPING INTO THE AORTA. 1076 00:50:59,196 --> 00:51:05,536 SHE HAD A VENTRICULAR SEPTAL 1077 00:51:05,536 --> 00:51:07,338 DEFECT, AS WELL AS -- NARROWING 1078 00:51:07,338 --> 00:51:09,607 OF THE BLOOD VESSEL THAT COMES 1079 00:51:09,607 --> 00:51:10,241 OFF THE HEART. 1080 00:51:10,241 --> 00:51:14,612 SO WE HAVE TO BURN -- HER 1081 00:51:14,612 --> 00:51:20,117 PHYSIOLOGY, YOU CAN SEE VENA 1082 00:51:20,117 --> 00:51:27,124 CAVAL FLOW, IT WAS ALL CROSSING 1083 00:51:27,124 --> 00:51:29,627 INTO HER LEFT ATRIUM. 1084 00:51:29,627 --> 00:51:31,062 ALL THE BLUE BLOOD IS GOING TO 1085 00:51:31,062 --> 00:51:32,163 HER LEFT ATRIAL SIDE. 1086 00:51:32,163 --> 00:51:39,370 IT WAS MIXING WITH HER FULLY 1087 00:51:39,370 --> 00:51:41,038 SATURATED BLOOD AND 1088 00:51:41,038 --> 00:51:42,239 CONSEQUENCELY WITH THIS 1089 00:51:42,239 --> 00:51:45,209 ADMIXTURE, SOME OF THAT FLOW WAS 1090 00:51:45,209 --> 00:51:48,145 GOING INTO -- ARTERIES, SOME WAS 1091 00:51:48,145 --> 00:51:50,681 GOING TO THE AORTA. 1092 00:51:50,681 --> 00:51:56,687 -- 75%. 1093 00:51:56,687 --> 00:51:59,323 SORTLY AFTER BIRTH SHE UNDERWENT 1094 00:51:59,323 --> 00:52:00,224 A PROCEDURE BASICALLY CONNECT 1095 00:52:00,224 --> 00:52:02,960 BEING THE PULMONARY ARTERY, 1096 00:52:02,960 --> 00:52:07,865 WHICH IS HERE, INTO THE AORTA. 1097 00:52:07,865 --> 00:52:10,368 SHE HAD A BTT SHUNT RIGHT HERE 1098 00:52:10,368 --> 00:52:14,338 TO ENSURE -- BECAUSE ONCE WE DID 1099 00:52:14,338 --> 00:52:19,977 THAT, IT CUT OFF HER ARTERY -- 1100 00:52:19,977 --> 00:52:23,114 THAT WAS DONE THROUGH THE SHUNT. 1101 00:52:23,114 --> 00:52:25,383 THEY ALSO DID A PARTIAL 1102 00:52:25,383 --> 00:52:28,119 CORRECTION OF HER -- BUT SHE 1103 00:52:28,119 --> 00:52:30,554 STILL HAD ACUTE -- AFTER HER 1104 00:52:30,554 --> 00:52:31,088 SURGERY. 1105 00:52:31,088 --> 00:52:37,862 HER NEXT PROCEDURE, THEY WENT 1106 00:52:37,862 --> 00:52:43,134 BACK AND THEY DID A REVISION. 1107 00:52:43,134 --> 00:52:45,002 HER LAST PROCEDURE -- OR NEXT 1108 00:52:45,002 --> 00:52:48,506 PROCEDURE WAS THE FONTAN 1109 00:52:48,506 --> 00:52:55,513 PROCEDURE. 1110 00:52:55,513 --> 00:53:00,317 BECAUSE WHEN THEY DID HER 1111 00:53:00,317 --> 00:53:01,919 INITIAL -- CASE CANCELED THIS, 1112 00:53:01,919 --> 00:53:03,854 IS NOT UNCOMMON BECAUSE THERE 1113 00:53:03,854 --> 00:53:06,357 WAS SCAR TISSUE HERE, THE 1114 00:53:06,357 --> 00:53:09,427 PULMONARY ARTERY WAS STENOTIC 1115 00:53:09,427 --> 00:53:11,729 OR -- THIS PRESSURE HAS TO BE 1116 00:53:11,729 --> 00:53:13,798 REMAIN UNDER AS LITTLE PRESSURE 1117 00:53:13,798 --> 00:53:16,767 AS POSSIBLE, SO WHENEVER WE 1118 00:53:16,767 --> 00:53:18,302 IDENTIFY ANY STENOSIS, WE HAVE 1119 00:53:18,302 --> 00:53:26,143 TO BE VERY -- ABOUT SEVEN YEARS 1120 00:53:26,143 --> 00:53:27,478 OF AGE. 1121 00:53:27,478 --> 00:53:35,619 FINALLY SHE HAD -- NOW AS A 1122 00:53:35,619 --> 00:53:37,588 RESULT OF ALL THE SURGERIES, HER 1123 00:53:37,588 --> 00:53:43,928 LEFT AND RIGHT ARE SEPARATED. 1124 00:53:43,928 --> 00:53:47,665 SO IF YOU LOOK AT HER INITIAL 1125 00:53:47,665 --> 00:53:50,167 ANATOMY, VERSUS WHAT HER FINAL 1126 00:53:50,167 --> 00:53:51,702 ANATOMY WAS, SHE'S NO LONGER 1127 00:53:51,702 --> 00:53:53,037 MIXING AND SHE WAS FULLY 1128 00:53:53,037 --> 00:53:57,842 SATURATED. 1129 00:53:57,842 --> 00:53:59,043 ONE OF THE THINGS, WE MAY TOUCH 1130 00:53:59,043 --> 00:54:02,012 ON THIS, ONE OF THE THINGS THAT 1131 00:54:02,012 --> 00:54:04,415 ADULTS WILL STILL HAVE IS SHE 1132 00:54:04,415 --> 00:54:07,785 HAS VENOUS CONNECTION WHICH 1133 00:54:07,785 --> 00:54:13,257 CONNECT FROM HER VENOUS SIDE 1134 00:54:13,257 --> 00:54:15,025 INTO AREAS OF HER ATRIUM, SO 1135 00:54:15,025 --> 00:54:17,561 BECAUSE OF THAT, THERE REMAINS 1136 00:54:17,561 --> 00:54:21,699 SOME RIGHT TO LEFT SHUNTING -- 1137 00:54:21,699 --> 00:54:25,102 FOR THAT REASON, SATURATION IS 1138 00:54:25,102 --> 00:54:29,640 STILL NOT 100% -- BUT COMPARING 1139 00:54:29,640 --> 00:54:32,009 TO WHERE SHE WAS BEFORE, 1140 00:54:32,009 --> 00:54:36,714 OBVIOUSLY THE FACT THAT SHE HAD 1141 00:54:36,714 --> 00:54:41,886 A CARDIAC MALFORMATION, THAT WAS 1142 00:54:41,886 --> 00:54:46,690 WHY -- ABOUT WHERE SHE HAS GONE, 1143 00:54:46,690 --> 00:54:53,130 AND SO NEXT I WANT TO INTRODUCE 1144 00:54:53,130 --> 00:54:56,133 HER MOTHER AND ANGELICA, WHO IS 1145 00:54:56,133 --> 00:54:58,536 OUR PATIENT FOR TODAY AND ONE OF 1146 00:54:58,536 --> 00:54:59,303 MY FAVORITE PATIENTS. 1147 00:54:59,303 --> 00:55:07,611 I'M GOING TO STOP SHARING. 1148 00:55:07,611 --> 00:55:08,312 HOW ARE YOU? 1149 00:55:08,312 --> 00:55:09,980 >> FINE, THANKS. 1150 00:55:09,980 --> 00:55:10,548 >> HI. 1151 00:55:10,548 --> 00:55:12,249 >> ANGELICA, HOW ARE YOU? 1152 00:55:12,249 --> 00:55:13,217 >> I'M GOOD. 1153 00:55:13,217 --> 00:55:14,318 HOW ARE YOU? 1154 00:55:14,318 --> 00:55:18,155 >> FIRST I WANT TO THANK YOU FOR 1155 00:55:18,155 --> 00:55:19,723 ACCEPTING OUR INVITATION TO 1156 00:55:19,723 --> 00:55:23,527 SPEAK WITH ME AND THEO ABOUT 1157 00:55:23,527 --> 00:55:26,630 YOUR HEART AND STUFF LIKE THAT. 1158 00:55:26,630 --> 00:55:28,032 SO JUST HAVE A -- WE'LL JUST GO 1159 00:55:28,032 --> 00:55:29,133 THROUGH A FEW THINGS AND THEN AT 1160 00:55:29,133 --> 00:55:32,870 THE END, WE'LL OPEN UP FOR -- 1161 00:55:32,870 --> 00:55:35,606 PROBABLY AFTER DR. HELLER'S 1162 00:55:35,606 --> 00:55:37,374 TALK, WE'LL OPEN UP FOR 1163 00:55:37,374 --> 00:55:38,542 QUESTIONS. 1164 00:55:38,542 --> 00:55:39,777 ANYWAY, ANGELICA, IF YOU DON'T 1165 00:55:39,777 --> 00:55:41,579 MIND INTRODUCING YOURSELF? 1166 00:55:41,579 --> 00:55:44,181 >> HI, I'M ANGELICA. 1167 00:55:44,181 --> 00:55:49,553 I'M 23. 1168 00:55:49,553 --> 00:55:54,391 DR. MER CLOA HAS BURKLOW HAS BER 1169 00:55:54,391 --> 00:55:57,061 SINCE I WAS 2. 1170 00:55:57,061 --> 00:55:59,096 I AM A TEACHER'S ASSISTANCE AT A 1171 00:55:59,096 --> 00:55:59,964 MONTESSORI SCHOOL, I'VE BEEN 1172 00:55:59,964 --> 00:56:01,232 WORKING THERE FOR ALMOST TWO 1173 00:56:01,232 --> 00:56:01,498 YEARS. 1174 00:56:01,498 --> 00:56:06,103 I LOVE WORKING WITH CHILDREN. 1175 00:56:06,103 --> 00:56:08,606 I WORK WITH 1 TO 3-YEAR-OLDS SO 1176 00:56:08,606 --> 00:56:13,244 I'M ALWAYS ON MY FEET 24/7, BUT 1177 00:56:13,244 --> 00:56:15,312 AGAIN, IT'S MY PASSION, IT MY 1178 00:56:15,312 --> 00:56:16,280 GREAT THING TO DO AND I GET TO 1179 00:56:16,280 --> 00:56:17,281 CHANGE THE WORLD AND HELP 1180 00:56:17,281 --> 00:56:20,584 CHILDREN. 1181 00:56:20,584 --> 00:56:22,553 >> THANK YOU, ANGELICA. 1182 00:56:22,553 --> 00:56:26,390 WE'LL COME BACK TO YOU IN A 1183 00:56:26,390 --> 00:56:26,724 SECOND. 1184 00:56:26,724 --> 00:56:28,359 YOU DON'T HAVE TO STATE YOUR AGE 1185 00:56:28,359 --> 00:56:29,693 BUT IF YOU WANT TO INTRODUCE 1186 00:56:29,693 --> 00:56:29,960 YOURSELF? 1187 00:56:29,960 --> 00:56:31,695 >> SURE, I'M ANGELICA'S MOM AND 1188 00:56:31,695 --> 00:56:33,030 YES, I WILL NOT SHARE MY AGE, 1189 00:56:33,030 --> 00:56:36,767 YOU GUYS CAN GUESS. 1190 00:56:36,767 --> 00:56:39,637 I HAVE ACTUALLY BEEN A 1191 00:56:39,637 --> 00:56:40,738 STAY-AT-HOME MOM SINCE THE DAY 1192 00:56:40,738 --> 00:56:42,039 SHE WAS BORN. 1193 00:56:42,039 --> 00:56:45,409 I'M A MILITARY NOW RETIRED AFTER 1194 00:56:45,409 --> 00:56:49,580 35 YEARS, A WIFE, I HAVE TWO 1195 00:56:49,580 --> 00:56:51,682 OTHER CHILDREN WHO ARE NOW 19 1196 00:56:51,682 --> 00:56:53,317 AND ALMOST 16. 1197 00:56:53,317 --> 00:56:55,519 I'VE JUST STARTED GOING BACK TO 1198 00:56:55,519 --> 00:56:57,454 WORKING THE LAST SEVERAL YEARS 1199 00:56:57,454 --> 00:56:59,556 AS A SOUTH ASIAN WEDDING 1200 00:56:59,556 --> 00:57:01,458 PLANNER. 1201 00:57:01,458 --> 00:57:05,796 >> THANK YOU. 1202 00:57:05,796 --> 00:57:08,932 SO CAN YOU SHARE YOUR THOUGHTS 1203 00:57:08,932 --> 00:57:10,968 WHEN YOU WERE FIRST INFORMED 1204 00:57:10,968 --> 00:57:13,137 ABOUT ANGELICA'S HEART 1205 00:57:13,137 --> 00:57:13,437 ABNORMALITY? 1206 00:57:13,437 --> 00:57:15,572 >> SURE. 1207 00:57:15,572 --> 00:57:17,975 GOSH, I FOUND OUT ACTUALLY WITH 1208 00:57:17,975 --> 00:57:20,377 HER HEART CONDITION WHEN I WAS 1209 00:57:20,377 --> 00:57:21,712 8 1/2 MONTHS PREGNANT. 1210 00:57:21,712 --> 00:57:23,547 SO AT THIS POINT -- AT THAT 1211 00:57:23,547 --> 00:57:24,548 POINT WE DIDN'T HAVE MUCH TIME 1212 00:57:24,548 --> 00:57:30,688 TO REALLY PREPARE OR EVEN 1213 00:57:30,688 --> 00:57:31,555 COMPREHEND WHAT WAS GOING ON AS 1214 00:57:31,555 --> 00:57:34,958 WE WERE SO CLOSE TO HER DUE 1215 00:57:34,958 --> 00:57:36,026 DATE. 1216 00:57:36,026 --> 00:57:40,798 WHEN WOULD WE FOUND OUT, THEY Y 1217 00:57:40,798 --> 00:57:42,533 MUCH TOLD US SHE WOULD NOT BE 1218 00:57:42,533 --> 00:57:43,734 VIABLE BASED ON WHAT THEY WERE 1219 00:57:43,734 --> 00:57:45,369 SEEING IN THE SONOGRAM, SO ON 1220 00:57:45,369 --> 00:57:46,603 AND SO FORTH. 1221 00:57:46,603 --> 00:57:50,541 SO WHEN WE HEARD THAT BETWEEN, 1222 00:57:50,541 --> 00:57:53,944 YOU KNOW, SHE BEING OUR FIRST 1223 00:57:53,944 --> 00:57:56,013 CHILD, I HAVE -- WHAT I RECALL 1224 00:57:56,013 --> 00:58:00,284 IS I DON'T EVEN -- I CAN'T EVEN 1225 00:58:00,284 --> 00:58:01,518 FULLY REMEMBER EXACTLY WHAT I 1226 00:58:01,518 --> 00:58:03,487 WAS DEALING WITH BECAUSE IT WAS 1227 00:58:03,487 --> 00:58:08,292 JUST LIKE OUR -- YOU KNOW, JUST 1228 00:58:08,292 --> 00:58:09,259 LIKE -- WHAT'S THE WORD I'M 1229 00:58:09,259 --> 00:58:11,895 LOOKING FOR, BUT IT JUST FELT 1230 00:58:11,895 --> 00:58:13,030 LIKE THE WORLD HAD DROPPED ON 1231 00:58:13,030 --> 00:58:16,200 OUR SHOULDER, BEING OUR FIRST 1232 00:58:16,200 --> 00:58:17,234 CHILD, BEING PARENTS FOR THE 1233 00:58:17,234 --> 00:58:20,738 FIRST TIME, AND THINGS LIKE 1234 00:58:20,738 --> 00:58:22,239 THAT, IT WAS JUST -- IT WAS 1235 00:58:22,239 --> 00:58:24,241 HARD. 1236 00:58:24,241 --> 00:58:28,579 >> YEAH. 1237 00:58:28,579 --> 00:58:30,481 AT THE TIME OF FETAL DIAGNOSIS 1238 00:58:30,481 --> 00:58:36,186 OR SHORTLY AFTER BIRTH, WE HAD 1239 00:58:36,186 --> 00:58:39,990 PEDIATRIC CARDIOLOGISTS WITH 1240 00:58:39,990 --> 00:58:41,291 OVERWHELMED PATIENTS, ESPECIALLY 1241 00:58:41,291 --> 00:58:48,565 WHEN YOU HAVE -- PEOPLE ARE 1242 00:58:48,565 --> 00:58:51,402 TALKING ABOUT SURGERY OVER THE 1243 00:58:51,402 --> 00:58:55,239 COURSE OF YEARS, THAT IS 1244 00:58:55,239 --> 00:58:58,876 OVERWHELMING. 1245 00:58:58,876 --> 00:59:00,411 TRICUSPID ATRESIA, EVEN FOR 1246 00:59:00,411 --> 00:59:02,546 MEDICAL FOLKS, IS NOT 1247 00:59:02,546 --> 00:59:04,915 NECESSARILY INTUITIVE, FOR 1248 00:59:04,915 --> 00:59:05,916 NON-MEDICAL FOLKS, PERHAPS EVEN 1249 00:59:05,916 --> 00:59:08,752 MORE SO. 1250 00:59:08,752 --> 00:59:10,053 HOW DID YOU SORT OF COME TO 1251 00:59:10,053 --> 00:59:13,056 UNDERSTAND HER ANATOMY AND 1252 00:59:13,056 --> 00:59:15,225 PHYSIOLOGY, AT LEAST IN A WAY 1253 00:59:15,225 --> 00:59:18,495 THAT IT ALLOWED YOU TO 1254 00:59:18,495 --> 00:59:19,630 UNDERSTAND WHAT SHE NEEDED? 1255 00:59:19,630 --> 00:59:21,799 >> WELL, I WAS VERY BLESSED, I 1256 00:59:21,799 --> 00:59:25,736 COULD SAY THAT WE HAD AMAZING 1257 00:59:25,736 --> 00:59:30,140 DOCTORS, INCLUDING DR. BURKLOW, 1258 00:59:30,140 --> 00:59:33,343 WE HAD OTHER DOCTORS OUT THERE 1259 00:59:33,343 --> 00:59:37,948 THAT ACTUALLY REASSURED US WHICH 1260 00:59:37,948 --> 00:59:38,816 WAS -- WE HADN'T HEARD I THINK 1261 00:59:38,816 --> 00:59:40,150 FOR THE FIRST TWO WEEKS OF THE 1262 00:59:40,150 --> 00:59:44,087 TIME OF OUR DIAGNOSIS, PRETTY 1263 00:59:44,087 --> 00:59:45,522 MUCH SAID SHE WILL NOT SURVIVE 1264 00:59:45,522 --> 00:59:51,228 AND THEN IN THE PROCESS OF 1265 00:59:51,228 --> 00:59:53,630 SEEING DIFFERENT DOCTORS AND 1266 00:59:53,630 --> 00:59:55,699 TALKING TO -- FINALLY WE HEARD 1267 00:59:55,699 --> 00:59:56,733 ONE OF THE DOCTORS SITTING THERE 1268 00:59:56,733 --> 00:59:57,801 TELLING US, WE CAN WORK WITH 1269 00:59:57,801 --> 00:59:58,135 THIS. 1270 00:59:58,135 --> 01:00:00,471 WE CAN WORK WITH THIS. 1271 01:00:00,471 --> 01:00:01,138 THIS CAN WORK. 1272 01:00:01,138 --> 01:00:02,339 THAT WAS THE FIRST TIME I THINK 1273 01:00:02,339 --> 01:00:07,244 I EVER HEARD, MIND YOU DURING 1274 01:00:07,244 --> 01:00:08,679 THIS WHOLE TIME I WAS GOING 1275 01:00:08,679 --> 01:00:10,013 THROUGH CONTRACTIONS, I THOUGHT 1276 01:00:10,013 --> 01:00:15,285 I WAS GOING TO GIVE BURT WITHOUH 1277 01:00:15,285 --> 01:00:17,054 WITHOUT HAPPENING AND WHEN I 1278 01:00:17,054 --> 01:00:18,422 HEARD HE COULD DO SOME SURGICAL 1279 01:00:18,422 --> 01:00:21,091 PROCEDURE AT THAT POINT, I THINK 1280 01:00:21,091 --> 01:00:22,226 MY CONTRACTIONS STOPPED AND I 1281 01:00:22,226 --> 01:00:24,728 JUST LOOKED AT MY HUSBAND SAYING 1282 01:00:24,728 --> 01:00:25,829 ALL RIGHT, WHERE DO WE SIGN THE 1283 01:00:25,829 --> 01:00:29,533 DOTTED LINE, WHERE DO WE -- SO 1284 01:00:29,533 --> 01:00:32,636 BECAUSE WE HAVE SUCH GOOD 1285 01:00:32,636 --> 01:00:36,907 DOCTORS EXPLAIN WHAT WAS THE 1286 01:00:36,907 --> 01:00:38,008 SITUATION, HOW TO GO ABOUT DOING 1287 01:00:38,008 --> 01:00:39,643 WHAT WE NEEDED TO DO TO SURVIVE 1288 01:00:39,643 --> 01:00:41,311 WAS A BLESSING, BECAUSE 1289 01:00:41,311 --> 01:00:42,412 OBVIOUSLY BEING FIRST-TIME 1290 01:00:42,412 --> 01:00:44,715 PARENTS AND NOT KNOWING WHAT 1291 01:00:44,715 --> 01:00:46,049 CONGENITAL HEART DISEASE OR ANY 1292 01:00:46,049 --> 01:00:49,887 TYPE OF HEART SITUATION WAS 1293 01:00:49,887 --> 01:00:51,955 KNOWN TO US, WE WERE VERY 1294 01:00:51,955 --> 01:00:53,490 BLESSED TO HAVING GREAT DOCTORS 1295 01:00:53,490 --> 01:00:59,129 TO EX-PLAINL TO US THROUGH A TO 1296 01:00:59,129 --> 01:01:02,065 Z, I WAS ABLE TO EXPLAIN THAT TO 1297 01:01:02,065 --> 01:01:03,267 MY FAMILY AND WHOEVER CAME 1298 01:01:03,267 --> 01:01:05,969 ACROSS THE PATH BUT WAY ABLE TO 1299 01:01:05,969 --> 01:01:10,107 TALK -- HAVE THE CONVERSATION, 1300 01:01:10,107 --> 01:01:11,441 SO YES, THANKS TO THE DOCTORS 1301 01:01:11,441 --> 01:01:14,411 AND EXPLAINING IN LAYMAN'S TERNL 1302 01:01:14,411 --> 01:01:19,182 MAN'S TERMSAND TREATING ME LIKEA 1303 01:01:19,182 --> 01:01:20,584 5-YEAR-OLD TO EXPLAIN WHAT HAS 1304 01:01:20,584 --> 01:01:22,553 COME ABOUT, HOW IT CAME ABOUT, 1305 01:01:22,553 --> 01:01:23,420 EVERYBODY DOESN'T UNDERSTAND 1306 01:01:23,420 --> 01:01:25,589 THAT BECAUSE IT'S A FLUKE HOW 1307 01:01:25,589 --> 01:01:27,324 THEY USE -- IN LEHMANN'S TERMS 1308 01:01:27,324 --> 01:01:30,060 AND HAVING DOCTORS EXPLAINING TO 1309 01:01:30,060 --> 01:01:32,863 US WAS -- WHAT WE NEEDED WAS 1310 01:01:32,863 --> 01:01:34,565 GREAT AND MAKE US UNDERSTAND. 1311 01:01:34,565 --> 01:01:37,334 >> ALTHOUGH ONE THING THAT'S 1312 01:01:37,334 --> 01:01:38,769 ALWAYS IMPRESSED ME WITH 1313 01:01:38,769 --> 01:01:43,206 FAMILIES LIKE YOU IS HOW 1314 01:01:43,206 --> 01:01:45,943 SOPHISTICATED YOU DO BECOME IN 1315 01:01:45,943 --> 01:01:46,910 UNDERSTANDING NOT JUST THE 1316 01:01:46,910 --> 01:01:48,412 ANATOMY BUT THE NEEDS, AND SO 1317 01:01:48,412 --> 01:01:52,783 GETTING PHONE CALLS FROM UM, 1318 01:01:52,783 --> 01:01:55,619 ESPECIALLY WHEN YOU WERE VERY 1319 01:01:55,619 --> 01:01:58,422 YOUNG, I KNEW THAT YOU WERE ABLE 1320 01:01:58,422 --> 01:02:02,025 TO RECOGNIZE CHANGES IN HER 1321 01:02:02,025 --> 01:02:04,962 ACTIVITIES OR EVALUATION. 1322 01:02:04,962 --> 01:02:11,468 SO I APPRECIATE THE -- I 1323 01:02:11,468 --> 01:02:13,437 DEEPLY -- I MEAN THIS SINCERELY, 1324 01:02:13,437 --> 01:02:16,607 I THINK YOU AND MATTHEW, 1325 01:02:16,607 --> 01:02:18,041 ANGELICA'S FATHER, HAVE MADE THE 1326 01:02:18,041 --> 01:02:21,144 DIFFERENCE IN HER LIFE TO MAKE 1327 01:02:21,144 --> 01:02:22,779 SURE SHE GOT THE CARE SHE 1328 01:02:22,779 --> 01:02:23,013 NEEDED. 1329 01:02:23,013 --> 01:02:25,616 >> THANK YOU. 1330 01:02:25,616 --> 01:02:30,587 >> IN THE YEARS, HOW -- CAN YOU 1331 01:02:30,587 --> 01:02:36,793 SHARE KIND OF GENERAL THOUGHTS 1332 01:02:36,793 --> 01:02:37,027 ABOUT -- 1333 01:02:37,027 --> 01:02:42,332 >> THE ONE THING I REMEMBER, DRD 1334 01:02:42,332 --> 01:02:43,967 I WAS STRUCK BY WAS TAKE HER 1335 01:02:43,967 --> 01:02:45,802 HOME, LOVE ON HER AS MUCH AS YOU 1336 01:02:45,802 --> 01:02:47,137 CAN, WE DON'T KNOW HOW MUCH TIME 1337 01:02:47,137 --> 01:02:48,905 SHE HAS, BUT MAKE SURE YOU DON'T 1338 01:02:48,905 --> 01:02:50,340 SPOIL HER SO SHE DOESN'T BECOME 1339 01:02:50,340 --> 01:02:52,743 A BRAT. 1340 01:02:52,743 --> 01:02:55,045 >> DID I SAY THAT? 1341 01:02:55,045 --> 01:02:55,245 OKAY. 1342 01:02:55,245 --> 01:02:57,147 >> I DON'T KNOW IF IT WAS THOSE 1343 01:02:57,147 --> 01:02:58,348 EXACT WORDS BUT I GOT THE GIST 1344 01:02:58,348 --> 01:02:59,683 OF IT AT THAT POINT. 1345 01:02:59,683 --> 01:03:02,319 AND THEY SAID WHAT YOU -- THEY 1346 01:03:02,319 --> 01:03:05,155 SAID JUST WATCHING HER, I MEAN, 1347 01:03:05,155 --> 01:03:09,526 ONE THING AFTER YOU TOLD US, 1348 01:03:09,526 --> 01:03:11,428 DON'T TREAT HER LIKE A PATIENT, 1349 01:03:11,428 --> 01:03:12,829 TREAT HER LIKE A NORMAL CHILD. 1350 01:03:12,829 --> 01:03:14,598 BECAUSE WHEN YOU TREAT A CHILD 1351 01:03:14,598 --> 01:03:16,166 OR ANY PERSON, IF YOU TREAT THEM 1352 01:03:16,166 --> 01:03:17,467 LIKE THEY'RE SICK, THAT'S WHAT 1353 01:03:17,467 --> 01:03:18,135 HAPPENS. 1354 01:03:18,135 --> 01:03:19,236 THEY BECOME SICK. 1355 01:03:19,236 --> 01:03:21,304 IF YOU TREAT THEM NORMALLY, 1356 01:03:21,304 --> 01:03:24,875 GIVEN THE ENVIRONMENT, THAT 1357 01:03:24,875 --> 01:03:27,611 HAPPY GO LUCKY BE AS NORMAL AS 1358 01:03:27,611 --> 01:03:28,578 POSSIBLEMENT LIFE WOULD BE 1359 01:03:28,578 --> 01:03:29,012 NORMAL. 1360 01:03:29,012 --> 01:03:32,249 SO OBVIOUSLY I DON'T -- A BLACK 1361 01:03:32,249 --> 01:03:35,018 CLOUD OVER OUR HEAD, I REMEMBER 1362 01:03:35,018 --> 01:03:37,487 ONE TIME WE WERE IN -- SITTING 1363 01:03:37,487 --> 01:03:39,022 THERE WATCHING WHEN SHE WAS 1364 01:03:39,022 --> 01:03:40,357 MAYBE LESS THAN A YEAR OLD, AND 1365 01:03:40,357 --> 01:03:46,396 WE WERE JUST TALKING AND I -- 1366 01:03:46,396 --> 01:03:48,665 NEAR THE COUCH WATCHING TV AND 1367 01:03:48,665 --> 01:03:51,134 SHE KIND OF BUCKLED OVER, I 1368 01:03:51,134 --> 01:03:52,669 THINK THAT WAS WHEN MY HEART -- 1369 01:03:52,669 --> 01:03:54,071 LIKE WHAT JUST HAPPENED, DID SHE 1370 01:03:54,071 --> 01:03:55,772 HAVE A HEART ATTACK, WAS IT 1371 01:03:55,772 --> 01:03:56,440 HEART FAILURE. 1372 01:03:56,440 --> 01:03:59,042 I REMEMBER BOTH MY HUSBAND AND I 1373 01:03:59,042 --> 01:04:01,111 ARE LIKE WHAT DO WE DO, WE 1374 01:04:01,111 --> 01:04:02,813 RUSHED OVER, SHE LITERALLY WENT 1375 01:04:02,813 --> 01:04:05,315 TO SLEEP AND HAD NO CARE, BUT 1376 01:04:05,315 --> 01:04:06,750 THOSE ARE THOSE KIND OF THINGS 1377 01:04:06,750 --> 01:04:10,721 THAT WE WERE VERY -- NOT REGARD 1378 01:04:10,721 --> 01:04:14,991 TO BEING -- WE WATCHED EVERY 1379 01:04:14,991 --> 01:04:16,193 GUIDANCE THAT WE GOT FROM ANY 1380 01:04:16,193 --> 01:04:20,630 DOCTOR, WE REALLY TOOK THAT AND 1381 01:04:20,630 --> 01:04:21,164 WAMPED IT. 1382 01:04:21,164 --> 01:04:23,467 WATCHED IT. 1383 01:04:23,467 --> 01:04:25,102 BUT AGAIN WE DEFINITELY TOOK 1384 01:04:25,102 --> 01:04:28,238 YOUR ADVICE AND MADE SURE SHE 1385 01:04:28,238 --> 01:04:29,206 DIDN'T TURN OUT TO BE A BRAT. 1386 01:04:29,206 --> 01:04:31,408 >> I STILL TURNED OUT TO BE A 1387 01:04:31,408 --> 01:04:31,608 BRAT. 1388 01:04:31,608 --> 01:04:34,077 >> I KNOW, BUT THAT'S THE 1389 01:04:34,077 --> 01:04:34,411 DIFFERENCE -- 1390 01:04:34,411 --> 01:04:35,512 >> THAT'S A TOPIC FOR ANOTHER 1391 01:04:35,512 --> 01:04:35,812 DAY. 1392 01:04:35,812 --> 01:04:38,048 >> SO ANGELICA, GROWING UP, WHAT 1393 01:04:38,048 --> 01:04:39,916 WAS YOUR FIRST SORT OF INKLING 1394 01:04:39,916 --> 01:04:40,884 THAT YOUR HEART WAS DIFFERENT 1395 01:04:40,884 --> 01:04:44,554 FROM OTHER KIDS? 1396 01:04:44,554 --> 01:04:48,625 >> LIKE MOM SAID, I WAS 1397 01:04:48,625 --> 01:04:50,694 FORTUNATE ENOUGH TO LIVE A 1398 01:04:50,694 --> 01:04:52,863 NORMAL LIFE AS I WORK IN -- I 1399 01:04:52,863 --> 01:04:56,633 WORK IN LIKE -- I WAS TOLD THAT 1400 01:04:56,633 --> 01:05:00,137 I WASN'T ABLE TO PLAY SPORTS, 1401 01:05:00,137 --> 01:05:02,472 SO -- AGAIN, THAT DIDN'T REALLY 1402 01:05:02,472 --> 01:05:06,643 STOP ME FROM DOING ANYTHING, SO 1403 01:05:06,643 --> 01:05:09,679 I FEEL -- I SING, I DANCE, I DO 1404 01:05:09,679 --> 01:05:12,082 EVERYTHING ELSE. 1405 01:05:12,082 --> 01:05:13,717 BUT I THINK IT WAS TOWARDS 1406 01:05:13,717 --> 01:05:15,519 MIDDLE SCHOOL TIME WHERE I WAS 1407 01:05:15,519 --> 01:05:17,821 TOLD, LIKE, HEY, SOMETHING IS 1408 01:05:17,821 --> 01:05:20,924 DIFFERENT WITH YOU BUT WE'RE NOT 1409 01:05:20,924 --> 01:05:24,694 GOING TO TREAT YOU ANY 1410 01:05:24,694 --> 01:05:30,767 DIFFERENT. 1411 01:05:30,767 --> 01:05:32,636 I HAD A PRETTY NORMAL CHILDHOOD 1412 01:05:32,636 --> 01:05:34,171 SO I DIDN'T REALLY FEEL ANY 1413 01:05:34,171 --> 01:05:34,437 DIFFERENT. 1414 01:05:34,437 --> 01:05:36,740 >> YOU DID KIND OF WHEN YOU HIT 1415 01:05:36,740 --> 01:05:37,073 SEVENTH GRADE. 1416 01:05:37,073 --> 01:05:41,211 I THINK YOU UNDERSTOOD -- WHEN 1417 01:05:41,211 --> 01:05:43,747 SHE WAS SEEING HER PEERS IN A 1418 01:05:43,747 --> 01:05:46,283 DIFFERENT WAY, THEY WERE 1419 01:05:46,283 --> 01:05:49,352 MATURING, THEY WERE -- 1420 01:05:49,352 --> 01:05:50,320 DIFFERENTLY THAN HER, I THINK 1421 01:05:50,320 --> 01:05:52,789 THAT'S WHEN SHE REALIZED THERE'S 1422 01:05:52,789 --> 01:05:54,324 SOMETHING DIFFERENT IN MY 1423 01:05:54,324 --> 01:05:57,060 RECORD, I'M NOT ABLE TO DO NOT 1424 01:05:57,060 --> 01:05:59,129 EVEN THE SPORTS, JUST IN 1425 01:05:59,129 --> 01:06:02,999 GENERAL, HOW HER -- WERE 1426 01:06:02,999 --> 01:06:03,967 DEVELOPING DIFFERENTLY, I THINK 1427 01:06:03,967 --> 01:06:06,269 THAT'S WHAT SHE REALIZED HER 1428 01:06:06,269 --> 01:06:07,270 DEVELOPMENT WAS DIFFERENT AT 1429 01:06:07,270 --> 01:06:11,341 THAT POINT, WHEN SHE UNDERSTOOD 1430 01:06:11,341 --> 01:06:12,976 THE -- AND ALSO UNDERSTAND THE 1431 01:06:12,976 --> 01:06:14,077 LONGEVITY OF HER LIFE, IS SHE 1432 01:06:14,077 --> 01:06:16,479 GOING TO LIVE LONGER OR 1433 01:06:16,479 --> 01:06:22,752 WHATEVER, SO -- WE STARTED TO 1434 01:06:22,752 --> 01:06:30,493 TALK TO -- FOR HER SITUATION. 1435 01:06:30,493 --> 01:06:32,195 >> GO AHEAD, I'M SORRY. 1436 01:06:32,195 --> 01:06:36,900 >> SO THEN I GOT HELP, GOT 1437 01:06:36,900 --> 01:06:38,101 THERAPY, BUT -- AND NOW I'M 1438 01:06:38,101 --> 01:06:39,202 HERE. 1439 01:06:39,202 --> 01:06:42,873 SO ALL GOOD. 1440 01:06:42,873 --> 01:06:45,709 >> ADOLESCENCE IS -- AND EVEN 1441 01:06:45,709 --> 01:06:53,250 OLD ADULTHOOD, YOU KNOW, IT'S A 1442 01:06:53,250 --> 01:06:56,052 MOMENT -- PSYCHOLOGICAL, SOCIAL 1443 01:06:56,052 --> 01:06:58,121 PRESSURE IN TERMS OF GROWING UP 1444 01:06:58,121 --> 01:07:00,523 AND WANTING TO FIT IN, WANTING 1445 01:07:00,523 --> 01:07:07,797 TO BE NORMAL, THAT IS A COMMON 1446 01:07:07,797 --> 01:07:08,064 STRUGGLE. 1447 01:07:08,064 --> 01:07:09,900 I THINK YOU ALL -- HOW DO YOU 1448 01:07:09,900 --> 01:07:15,839 ADDRESS THAT AND HOW DO YOU -- 1449 01:07:15,839 --> 01:07:18,241 SIMPLY TRYING TO FIX IT BY 1450 01:07:18,241 --> 01:07:22,946 YOURSELF, THERAPY -- DOING WELL. 1451 01:07:22,946 --> 01:07:25,181 SO WE'LL JUST KIND OF WRAP UP. 1452 01:07:25,181 --> 01:07:29,252 IS THERE -- HOW DO YOU -- LIKE 1453 01:07:29,252 --> 01:07:30,487 NOWADAYS, SO YOU'RE WORKING, 1454 01:07:30,487 --> 01:07:32,255 YOU'VE BEEN A TEACHER ASSISTANT 1455 01:07:32,255 --> 01:07:33,757 FOR A COUPLE YEARS AND I KNOW 1456 01:07:33,757 --> 01:07:35,725 THAT YOU LOVE KID, AND I THINK 1457 01:07:35,725 --> 01:07:38,929 THAT'S SUPER. 1458 01:07:38,929 --> 01:07:41,264 IS THERE -- HAVING YOUR HEART 1459 01:07:41,264 --> 01:07:43,767 DISEASE, IS THAT -- DO YOU FEEL 1460 01:07:43,767 --> 01:07:45,068 LIKE IT AFFECT YOU, DO YOU THINK 1461 01:07:45,068 --> 01:07:46,937 ABOUT IT ON A DAILY BASIS OR 1462 01:07:46,937 --> 01:07:47,103 NOT? 1463 01:07:47,103 --> 01:07:49,706 >> HONESTLY, THERE ARE TIMES 1464 01:07:49,706 --> 01:07:53,109 WHERE LIKE I FEEL SO NORMAL 1465 01:07:53,109 --> 01:07:55,679 THAT, LIKE, I FORGET I HAVE A 1466 01:07:55,679 --> 01:08:02,118 SCAR, OR I FORGET THAT I HAVE A 1467 01:08:02,118 --> 01:08:06,289 HALF A HEART, I FELT MYSELF 1468 01:08:06,289 --> 01:08:06,623 NORMAL. 1469 01:08:06,623 --> 01:08:07,991 SO NO, TO ANSWER YOUR QUESTION 1470 01:08:07,991 --> 01:08:09,292 I'VE NEVER REALLY -- IT'S 1471 01:08:09,292 --> 01:08:11,361 JUST -- I HAVE IT, IT'S 1472 01:08:11,361 --> 01:08:12,729 SOMETHING I LIVED WITH ALL MY 1473 01:08:12,729 --> 01:08:14,698 LIFE AND I WILL CONTINUE TO LIVE 1474 01:08:14,698 --> 01:08:16,366 WITH, BUT NO, IT DOESN'T REALLY 1475 01:08:16,366 --> 01:08:18,401 AFFECT ME. 1476 01:08:18,401 --> 01:08:21,304 I DON'T REALLY -- UNTIL 1477 01:08:21,304 --> 01:08:23,373 SOMETHING, LIKE, IF YOU HAVE AN 1478 01:08:23,373 --> 01:08:25,575 APPOINTMENT OR SURGERY OR 1479 01:08:25,575 --> 01:08:26,343 WHATEVER, BUT OTHER THAN THAT, 1480 01:08:26,343 --> 01:08:31,114 IT BARELY COMES TO MY MIND. 1481 01:08:31,114 --> 01:08:32,949 >> SHE WANTS TO SAY THIS IS A 1482 01:08:32,949 --> 01:08:34,684 PART OF ME, AND I THINK FOR HER, 1483 01:08:34,684 --> 01:08:36,486 I BELIEVE THAT THAT HAS BEEN HER 1484 01:08:36,486 --> 01:08:37,020 SAVING GRACE. 1485 01:08:37,020 --> 01:08:38,221 I BELIEVE THAT HER SAYING YOU 1486 01:08:38,221 --> 01:08:44,694 KNOW WHAT, I'M JUST GOING TO 1487 01:08:44,694 --> 01:08:46,262 KEEP ON GOING EVERY DAY AND NOT 1488 01:08:46,262 --> 01:08:47,597 LET THIS HOLD ME BACK IN ANY 1489 01:08:47,597 --> 01:08:48,465 WAY. 1490 01:08:48,465 --> 01:08:50,100 WHICH AS PARENTS WE'VE ALWAYS 1491 01:08:50,100 --> 01:08:53,003 PUSHED, DO NOT ALLOW THIS TO 1492 01:08:53,003 --> 01:08:54,070 HOLD YOU BACK BECAUSE FOR ALL 1493 01:08:54,070 --> 01:08:56,373 YOU KNOW, YOU'LL BE HERE UNTIL 1494 01:08:56,373 --> 01:09:00,276 YOU'RE 100 YEARS OLD, YOU KNOW? 1495 01:09:00,276 --> 01:09:01,911 YOU KNOW HOWL TO DISCONNECT. 1496 01:09:01,911 --> 01:09:02,979 >> IS THERE ANYTHING YOU FEEL 1497 01:09:02,979 --> 01:09:04,814 LIKE YOU CAN'T DO THAT YOU WANT 1498 01:09:04,814 --> 01:09:08,318 TO DO? 1499 01:09:08,318 --> 01:09:12,489 >> NO. 1500 01:09:12,489 --> 01:09:20,230 >> I GO -- 1501 01:09:20,230 --> 01:09:24,934 >> I MEAN, I'VE GONE ON 1502 01:09:24,934 --> 01:09:26,536 HELICOPTERS, I GREW UP -- DURING 1503 01:09:26,536 --> 01:09:28,171 MY 12 YEARS OF SCHOOL, I WAS 1504 01:09:28,171 --> 01:09:30,473 ABLE TO BE WITH MY PEERS, PLAY 1505 01:09:30,473 --> 01:09:34,944 BASKETBALL, PLAY SOCCER, BEING 1506 01:09:34,944 --> 01:09:36,046 ABLE TO BE WITH THEM BUT AT THE 1507 01:09:36,046 --> 01:09:37,714 SAME TIME I KNEW MY LIMITS AND 1508 01:09:37,714 --> 01:09:39,149 WHEN I NEED TO SIT OUT, WHEN I 1509 01:09:39,149 --> 01:09:43,019 NEEDED TO TAKE A BREAK. 1510 01:09:43,019 --> 01:09:45,989 NOBODY JUDGED ME, I TOLD ALL MY 1511 01:09:45,989 --> 01:09:48,158 TEACHERS LIKE HEY, THIS IS MY -- 1512 01:09:48,158 --> 01:09:52,562 I'M ALLOWED TO DO EVERYTHING, 1513 01:09:52,562 --> 01:09:54,564 I'LL LET YOU KNOW WHEN I NEED TO 1514 01:09:54,564 --> 01:09:55,098 SIT OUT. 1515 01:09:55,098 --> 01:09:58,068 I DID THAT AND I NEVER HAD A 1516 01:09:58,068 --> 01:10:08,344 PROBLEM WITH IT. 1517 01:10:14,384 --> 01:10:17,587 >> SO BEFORE WE TURN OVER TO DRG 1518 01:10:17,587 --> 01:10:25,228 YOU WANT TO ADD TO WHAT WE'VE 1519 01:10:25,228 --> 01:10:35,572 BEEN TALKING ABOUT? 1520 01:10:36,506 --> 01:10:39,075 >> EVERYTHING GO GREAT, 1521 01:10:39,075 --> 01:10:41,344 EVERYTHING WILL BE FINE. 1522 01:10:41,344 --> 01:10:42,979 >> AND BELIEVE IN YOUR 1523 01:10:42,979 --> 01:10:43,246 DOCTORS -- 1524 01:10:43,246 --> 01:10:48,318 >> AND DOCTORS, YES. 1525 01:10:48,318 --> 01:10:50,019 >> WE'LL TURN YOUR CAMERAS OFF 1526 01:10:50,019 --> 01:10:52,322 AND LET DR. HELLER SPEAK. 1527 01:10:52,322 --> 01:10:52,655 >> THANK YOU. 1528 01:10:52,655 --> 01:11:02,999 >> OKAY, THANK YOU. 1529 01:11:12,142 --> 01:11:14,677 >> THANK YOU VERY MUCH. 1530 01:11:14,677 --> 01:11:18,515 THANK YOU TO ANGELICA AND HER 1531 01:11:18,515 --> 01:11:20,383 MOTHER FOR JUST SHOWING PEOPLE 1532 01:11:20,383 --> 01:11:21,684 THE IMMEDIATE RELEVANCE OF WHAT 1533 01:11:21,684 --> 01:11:22,952 WE DO. 1534 01:11:22,952 --> 01:11:27,157 AND WHAT IT MEANS TO PATIENTS 1535 01:11:27,157 --> 01:11:28,725 AND TO PEOPLE TO HAVE MEDICAL 1536 01:11:28,725 --> 01:11:30,627 PROFESSIONALS LIKE DR. BURKLOW 1537 01:11:30,627 --> 01:11:32,061 WHO ARE SO VESTED IN THEIR CARE. 1538 01:11:32,061 --> 01:11:33,496 IT'S NOT OFTEN THAT A DOCTOR CAN 1539 01:11:33,496 --> 01:11:34,964 SAY I'VE KNOWN YOU FROM BEFORE 1540 01:11:34,964 --> 01:11:39,769 YOU WERE BORN AND STILL BE 1541 01:11:39,769 --> 01:11:40,637 INVOLVED WITH YOUR CARE AND 1542 01:11:40,637 --> 01:11:43,773 STILL HAVE A RELATION SHIM. 1543 01:11:43,773 --> 01:11:44,641 RELATIONSHIP. 1544 01:11:44,641 --> 01:11:45,842 IT'S INSPIRING AND HUMBLING. 1545 01:11:45,842 --> 01:11:47,477 I ALSO WANT TO THANK DR. ARIAS 1546 01:11:47,477 --> 01:11:48,611 AND DR. KASTNER FOR THE 1547 01:11:48,611 --> 01:11:51,147 INVITATION AND FOR CHRIS, FOR 1548 01:11:51,147 --> 01:11:55,251 PUTTING UP WITH MY EMAIL FETISH. 1549 01:11:55,251 --> 01:12:00,590 THE TITLE OF MY TALK IS FONTAN 1550 01:12:00,590 --> 01:12:02,325 ASSOCIATED LIVER DISEASE OR 1551 01:12:02,325 --> 01:12:05,195 DON'T GET EXTINGUISHED. 1552 01:12:05,195 --> 01:12:07,864 THE FONTAN PALLIATION THAT 1553 01:12:07,864 --> 01:12:14,671 DR. BUT C BURKLOW EXPLAINED SO . 1554 01:12:14,671 --> 01:12:16,105 HERE ARE MY DISCLOSURES. 1555 01:12:16,105 --> 01:12:17,507 TODAY WE'RE GOING TO START BY 1556 01:12:17,507 --> 01:12:19,042 TALKING ABOUT THE LIVER. 1557 01:12:19,042 --> 01:12:20,743 AND WE'RE GOING TO THINK ABOUT 1558 01:12:20,743 --> 01:12:21,945 LIVER DISEASE, REVIEW THE 1559 01:12:21,945 --> 01:12:26,216 CURRENT UNDERSTANDING OF FONTAN 1560 01:12:26,216 --> 01:12:27,650 ASSOCIATED LIVER DISEASE, AND 1561 01:12:27,650 --> 01:12:30,286 ITS UNIQUENESS, AND TO 1562 01:12:30,286 --> 01:12:31,054 UNDERSTAND WHY IT IS WE'D BE 1563 01:12:31,054 --> 01:12:34,557 INTERESTED IN IT, AND THEN TALK 1564 01:12:34,557 --> 01:12:36,492 ABOUT WHAT LIMITS THE STUDY OF 1565 01:12:36,492 --> 01:12:38,027 FALD AND BE FRUSTRATED BY THE 1566 01:12:38,027 --> 01:12:38,895 LACK OF UNDERSTANDING. 1567 01:12:38,895 --> 01:12:41,231 I HOPE WE ALL END UP VERY 1568 01:12:41,231 --> 01:12:42,198 FRUSTRATED AND THEN BECOME 1569 01:12:42,198 --> 01:12:43,099 EXCITED ABOUT THE OPPORTUNITIES 1570 01:12:43,099 --> 01:12:44,834 TO EXPLORE FALD AND THINK ABOUT 1571 01:12:44,834 --> 01:12:46,302 WHAT WE CAN DO TO CHANGE THE 1572 01:12:46,302 --> 01:12:49,372 FIELD. 1573 01:12:49,372 --> 01:12:50,340 SO LET'S TALK ABOUT THE LIVER. 1574 01:12:50,340 --> 01:12:54,177 WHY SHOULD YOU LOVE YOUR LIVER? 1575 01:12:54,177 --> 01:12:55,778 WELL, I AGREE THE HEART IS 1576 01:12:55,778 --> 01:12:56,846 IMPORTANT BUT THE LIVER IS THE 1577 01:12:56,846 --> 01:12:58,047 MOST IMPORTANT ORGAN IN YOUR 1578 01:12:58,047 --> 01:12:59,482 BODY, AND IF WE THINK ABOUT WHAT 1579 01:12:59,482 --> 01:13:04,554 IT DOES, IF IT MAKES SO MANY 1580 01:13:04,554 --> 01:13:06,222 COMPOUNDS, CLOTTING FACTORS, YOU 1581 01:13:06,222 --> 01:13:07,423 WOULDN'T BE ABLE TO HAVE SURGERY 1582 01:13:07,423 --> 01:13:10,326 AND HEAL IF THE LIVER DIDN'T 1583 01:13:10,326 --> 01:13:11,961 MAKE CLOTTING FACTORS. 1584 01:13:11,961 --> 01:13:15,265 IT BREAKS DOWN PRODUCTS, THINK 1585 01:13:15,265 --> 01:13:16,599 ABOUT FEDEX, THEY HAVE HUBS, SO 1586 01:13:16,599 --> 01:13:18,434 LOTS OF DIFFERENT PACKAGES COME 1587 01:13:18,434 --> 01:13:19,769 INTO HUBS, SAY CINCINNATI AND 1588 01:13:19,769 --> 01:13:22,438 THEN THEY GET SORTED AND SENT 1589 01:13:22,438 --> 01:13:23,973 OFF, SO EVERYTHING WE EAT, 1590 01:13:23,973 --> 01:13:26,709 LIPIDS, PROTEINS, AMINO ACIDS, 1591 01:13:26,709 --> 01:13:28,211 GLUCOSE, COMES TO THE LIVER, 1592 01:13:28,211 --> 01:13:30,813 GETS SORTED OUT, BROKEN DOWN, 1593 01:13:30,813 --> 01:13:32,248 PACKAGED, REPACKAGED AND THEN 1594 01:13:32,248 --> 01:13:33,049 SENT OUT. 1595 01:13:33,049 --> 01:13:35,151 IT STORES THINGS LIKE VITAMIN A, 1596 01:13:35,151 --> 01:13:37,120 VITAMIN D, REPACKAGES THINGS. 1597 01:13:37,120 --> 01:13:38,488 WE SPOKE ABOUT THAT. 1598 01:13:38,488 --> 01:13:42,191 IT CLEANS AND DETOXIFIES. 1599 01:13:42,191 --> 01:13:42,859 IT PROTECTS. 1600 01:13:42,859 --> 01:13:44,294 IT'S THE LAST BARRIER. 1601 01:13:44,294 --> 01:13:46,829 WHEN YOU EAT SOMETHING REALLY 1602 01:13:46,829 --> 01:13:52,201 BAD, AN EVIL VIRUS, BACTERIA, IT 1603 01:13:52,201 --> 01:13:54,604 GETS INTO THE LAST OPPORTUNITY 1604 01:13:54,604 --> 01:13:56,005 YOUR BODY HAS TO PREVENT IT FROM 1605 01:13:56,005 --> 01:13:57,407 COMING INSIDE YOU. 1606 01:13:57,407 --> 01:13:58,941 SO WHEN I WAS IN MEDICAL SCHOOL, 1607 01:13:58,941 --> 01:14:03,146 THEY SPOKE ABOUT 19 MAJOR LIVER 1608 01:14:03,146 --> 01:14:04,781 FUNCTIONS, NOW IT'S OVER 500. 1609 01:14:04,781 --> 01:14:08,284 LIVER DOES LOTS AND LOTS. 1610 01:14:08,284 --> 01:14:10,687 WHAT CAN GO WRONG? 1611 01:14:10,687 --> 01:14:11,621 THE CLASSIC THING IS 1612 01:14:11,621 --> 01:14:16,326 INFLAMMATION AND THEN SCARRING. 1613 01:14:16,326 --> 01:14:17,393 THAT'S PRETTY MUCH WHAT HAPPENS 1614 01:14:17,393 --> 01:14:18,594 NO MATTER WHAT YOU DO TO THE 1615 01:14:18,594 --> 01:14:18,995 LIVER. 1616 01:14:18,995 --> 01:14:21,297 TOO MUCH IRON, TOO MUCH FAT, 1617 01:14:21,297 --> 01:14:23,266 VIRUSES, ALCOHOL, AND WHEN THAT 1618 01:14:23,266 --> 01:14:26,035 HAPPENS, WHEN THAT REACHES A 1619 01:14:26,035 --> 01:14:26,903 CERTAIN POINT, THE LIVER 1620 01:14:26,903 --> 01:14:28,571 FUNCTION BECOMES IMPAIRED AND 1621 01:14:28,571 --> 01:14:33,910 THE PRESSURE INCREASES. 1622 01:14:33,910 --> 01:14:36,379 LET'S START BY TALKING ABOUT THE 1623 01:14:36,379 --> 01:14:37,046 INFLAMMATION. 1624 01:14:37,046 --> 01:14:38,581 WE OFTEN TALK ABOUT LIVER 1625 01:14:38,581 --> 01:14:39,916 ENZYMES AS LIVER FUNCTION TESTS 1626 01:14:39,916 --> 01:14:41,784 BUT THEY'RE NOT. 1627 01:14:41,784 --> 01:14:44,420 LT AND ST REFLECT THE MOOD THE 1628 01:14:44,420 --> 01:14:44,854 LIVER IS IN. 1629 01:14:44,854 --> 01:14:46,289 I CAN BE AT HOME SITTING ON THE 1630 01:14:46,289 --> 01:14:47,423 COUCH, AND I HAVE TO TAKE OUT 1631 01:14:47,423 --> 01:14:48,391 THE TRASH. 1632 01:14:48,391 --> 01:14:50,927 I CAN BE IN A FANTASTIC MOOD AND 1633 01:14:50,927 --> 01:14:52,829 STAY ON THE COUCH. 1634 01:14:52,829 --> 01:14:54,497 MY LT COULD BE NORMAL AND THE 1635 01:14:54,497 --> 01:14:55,698 LIVER IS DOING ALL THOSE 1636 01:14:55,698 --> 01:14:57,333 FUNCTIONS WE JUST SPOKE ABOUT. 1637 01:14:57,333 --> 01:15:00,103 OR I COULD BE -- I STAND UP AND 1638 01:15:00,103 --> 01:15:02,638 I USE BAD LANGUAGE, LIKE NO, AND 1639 01:15:02,638 --> 01:15:04,273 I DON'T WANT TO DO THIS. 1640 01:15:04,273 --> 01:15:07,076 AND I TAKE OUT THE TRASH. 1641 01:15:07,076 --> 01:15:09,946 SO THE LT CAN BE ELEVATED AND 1642 01:15:09,946 --> 01:15:11,280 THE LIVER CAN STILL BE 1643 01:15:11,280 --> 01:15:12,148 PERFORMING ITS CHORES. 1644 01:15:12,148 --> 01:15:14,217 AND I CANNOT EMPHASIZE THIS 1645 01:15:14,217 --> 01:15:15,184 ENOUGH. 1646 01:15:15,184 --> 01:15:17,553 PEOPLE OFTEN TALK TO US ABOUT MY 1647 01:15:17,553 --> 01:15:18,855 LT WENT UP, MY LIVER IS DOING 1648 01:15:18,855 --> 01:15:19,188 WORSE. 1649 01:15:19,188 --> 01:15:19,722 THAT'S NOT TRUE. 1650 01:15:19,722 --> 01:15:21,591 THE LIVER IS IN A WORSE MOOD AND 1651 01:15:21,591 --> 01:15:23,826 THE LONGER THE LIVER IS IN A BAD 1652 01:15:23,826 --> 01:15:25,695 MOOD, THE MORE LIKELY IT IS IT 1653 01:15:25,695 --> 01:15:26,796 WON'T FUNCTION BUT THE TWO ARE 1654 01:15:26,796 --> 01:15:30,466 NOT IMMEDIATELY CORRELATED. 1655 01:15:30,466 --> 01:15:32,869 SO IN CIRRHOSIS, AND WHEN THE 1656 01:15:32,869 --> 01:15:36,606 LIVER REACHES A POINT OF ENOUGH 1657 01:15:36,606 --> 01:15:37,874 SCARRING, THE LIVER STOPS DOING 1658 01:15:37,874 --> 01:15:38,408 ITS CHORES. 1659 01:15:38,408 --> 01:15:40,476 ALL THOSE THINGS WE SPOKE ABOUT, 1660 01:15:40,476 --> 01:15:42,779 IT STOPS DOING ITS HOMEWORK, 1661 01:15:42,779 --> 01:15:44,046 MAKING ITS BED, TAKING OUT THE 1662 01:15:44,046 --> 01:15:44,914 TRASH. 1663 01:15:44,914 --> 01:15:46,449 AND THAT'S A FUNCTIONAL PROBLEM. 1664 01:15:46,449 --> 01:15:47,817 BUT I'M GOING TO TALK A LITTLE 1665 01:15:47,817 --> 01:15:50,987 BIT MORE ABOUT PRESSURE. 1666 01:15:50,987 --> 01:15:52,155 THE LIVER HAS ITS OWN BLOOD 1667 01:15:52,155 --> 01:15:53,489 PRESSURE AND IF IT'S HIGH, IT'S 1668 01:15:53,489 --> 01:15:55,191 CALLED PORTAL HYPERTENSION, AND 1669 01:15:55,191 --> 01:15:56,526 THERE ARE MANY REASONS FOR THE 1670 01:15:56,526 --> 01:15:58,060 PRESSURE TO BECOME ELEVATED BUT 1671 01:15:58,060 --> 01:15:59,896 THE COMMONEST IS CIRRHOSIS 1672 01:15:59,896 --> 01:16:02,799 INSIDE THE LIVER. 1673 01:16:02,799 --> 01:16:04,133 OR SCARRING IN THE LIVER THAT'S 1674 01:16:04,133 --> 01:16:06,102 REACHED THE POINT WHERE IT'S NOW 1675 01:16:06,102 --> 01:16:10,106 IMPAIRING FUNCTION AND PRESSURE. 1676 01:16:10,106 --> 01:16:12,175 YOU MIGHT HAVE HEARD OF SOMEONE 1677 01:16:12,175 --> 01:16:14,143 CALLED MEGAN TRAINOR, SHE HAD A 1678 01:16:14,143 --> 01:16:15,244 SON, IT WAS ALL ABOUT THE 1679 01:16:15,244 --> 01:16:16,479 PRESSURE BUT SHE COULDN'T SELL 1680 01:16:16,479 --> 01:16:18,214 IT SO SHE CHANGED TO IT'S ALL 1681 01:16:18,214 --> 01:16:20,783 ABOUT THE BASS BUT IT REALLY ALL 1682 01:16:20,783 --> 01:16:21,651 ABOUT THE PRESSURE. 1683 01:16:21,651 --> 01:16:22,852 WHAT HAPPENS IS THERE'S NO 1684 01:16:22,852 --> 01:16:23,986 SYMPTOMS DELAYED AND IT TAKES 1685 01:16:23,986 --> 01:16:25,421 TIME TO DEVELOP THIS. 1686 01:16:25,421 --> 01:16:26,889 IN ALL OF A DISEASE, IN MOST 1687 01:16:26,889 --> 01:16:31,727 LIVER DISEASE, THIS IS TRUE. 1688 01:16:31,727 --> 01:16:35,398 CLASSIC COMPLICATIONS, SPLE 1689 01:16:35,398 --> 01:16:42,605 KNOWMSPLENOMEGALY, WHEN WE THINK 1690 01:16:42,605 --> 01:16:44,307 ABOUT WHY PEOPLE DIE WITH LIVER 1691 01:16:44,307 --> 01:16:47,276 DISEASE, THESE ARE THE 1692 01:16:47,276 --> 01:16:48,344 REASONS -- LIVER CANCER. 1693 01:16:48,344 --> 01:16:52,815 MAJOR REASONS OF CAUSE OF DEATH 1694 01:16:52,815 --> 01:16:53,983 EVEN IN CIRRHOSIS IS THE 1695 01:16:53,983 --> 01:16:54,550 PRESSURE. 1696 01:16:54,550 --> 01:16:56,052 THIS IS WHAT VARICES LOOK LIKE. 1697 01:16:56,052 --> 01:16:59,789 THIS IS A PICTURE OF A PATIENT 1698 01:16:59,789 --> 01:17:00,957 WITH FULL COLUMNS OF VARICES AND 1699 01:17:00,957 --> 01:17:03,559 THE BOTTOM HALF, THE VARICES ARE 1700 01:17:03,559 --> 01:17:04,994 BIGGER AND YOU CAN SEE IT LOOKS 1701 01:17:04,994 --> 01:17:09,131 LIKE SNAKES GOING DOWN. 1702 01:17:09,131 --> 01:17:11,734 THE ESOPHAGUS, STOMACH, RECTUM, 1703 01:17:11,734 --> 01:17:14,036 OTHER PARTS OF THE 1704 01:17:14,036 --> 01:17:15,037 GASTROINTESTINAL TRACT OR BODY, 1705 01:17:15,037 --> 01:17:17,540 AND THE PROBLEM IN THE ESOPHAGUS 1706 01:17:17,540 --> 01:17:19,342 AND SOMETIMES THE RECTUM IS THAT 1707 01:17:19,342 --> 01:17:22,345 THE PRESSURE GETS VERY HIGH AND 1708 01:17:22,345 --> 01:17:23,579 THEY BEING BREAK OFF AND BLEED 1709 01:17:23,579 --> 01:17:25,314 AND IN CASE YOU'RE WONDERING, 1710 01:17:25,314 --> 01:17:26,282 THE BLEEDING IS BAD. 1711 01:17:26,282 --> 01:17:27,583 IT'S NOT GOOD. 1712 01:17:27,583 --> 01:17:28,651 SUBOPTIMAL. 1713 01:17:28,651 --> 01:17:31,387 AND THIS IS HOW IT HAPPENS. 1714 01:17:31,387 --> 01:17:32,588 IT'S ALL ABOUT THE LIVER AND 1715 01:17:32,588 --> 01:17:34,624 THIS IS HOW THE VARICES OCCUR. 1716 01:17:34,624 --> 01:17:36,926 YOU HAVE THE GUT, AND THE 1717 01:17:36,926 --> 01:17:38,561 SPLEEN, AND FOR THOSE WHO DON'T 1718 01:17:38,561 --> 01:17:39,529 KNOW THAT'S WHAT THE SPLEEN 1719 01:17:39,529 --> 01:17:40,396 LOOKS LIKE. 1720 01:17:40,396 --> 01:17:43,132 AND THE BLOOD GOES FROM THE GUT, 1721 01:17:43,132 --> 01:17:44,767 AND FROM THE SPLEEN INTO THE 1722 01:17:44,767 --> 01:17:45,635 MOST IMPORTANT ORGAN IN THE 1723 01:17:45,635 --> 01:17:48,271 BODY. 1724 01:17:48,271 --> 01:17:49,639 IN CASE I DIDN'T SAY IT, IT IS 1725 01:17:49,639 --> 01:17:51,274 THE MOST IMPORTANT ORGAN IN THE 1726 01:17:51,274 --> 01:17:52,808 BODY, THE LIVER. 1727 01:17:52,808 --> 01:17:54,744 FROM THE LIVER, IT GOES BACK TO 1728 01:17:54,744 --> 01:17:56,145 THE HEART AND FOR THOSE WHO 1729 01:17:56,145 --> 01:17:57,146 DIDN'T GO TO MEDICAL SCHOOL, 1730 01:17:57,146 --> 01:17:58,014 THAT'S WHAT THE HEART REALLY 1731 01:17:58,014 --> 01:18:02,385 LOOKS LIKE. 1732 01:18:02,385 --> 01:18:04,186 IF YOU THINK ABOUT IT NOW, IF 1733 01:18:04,186 --> 01:18:05,955 THERE'S A BLOCKAGE IN THE LIVER, 1734 01:18:05,955 --> 01:18:08,291 IT SIMPLE PLUMBING. 1735 01:18:08,291 --> 01:18:09,458 THERE WILL BE BACK PRESSURE TO 1736 01:18:09,458 --> 01:18:10,726 THE GUT, BACK PRESSURE TO THE 1737 01:18:10,726 --> 01:18:13,563 SPLEEN, THE SPLE SPLEEN WILL GET 1738 01:18:13,563 --> 01:18:13,896 BIGGER. 1739 01:18:13,896 --> 01:18:16,032 PART OF THE SPLEEN'S JOB IS TO 1740 01:18:16,032 --> 01:18:17,466 RECYCLE PLATELETS WHICH IS WHY 1741 01:18:17,466 --> 01:18:19,201 THE PLATELETS DROP AS THE SPLEEN 1742 01:18:19,201 --> 01:18:19,769 GETS BIG. 1743 01:18:19,769 --> 01:18:21,270 BUT THE BLOOD HAS THIS OBSESSION 1744 01:18:21,270 --> 01:18:22,872 WITH GETTING BACK TO THE HEART. 1745 01:18:22,872 --> 01:18:25,708 SO THAT IT CAN GET OXYGENATED, 1746 01:18:25,708 --> 01:18:27,376 WHICH DR. BUT CLOA EXPLAINED, 1747 01:18:27,376 --> 01:18:29,512 AND THAT'S WHEN VARICES FORM. 1748 01:18:29,512 --> 01:18:31,581 THEY ARE COLLATERALS, OR THEY 1749 01:18:31,581 --> 01:18:36,886 ARE VESSELS THAT BY IT IS BASS S 1750 01:18:36,886 --> 01:18:37,987 THE LIVER SO THE BLOOD CAN 1751 01:18:37,987 --> 01:18:38,988 RETURN TO THE HEART BECAUSE OF 1752 01:18:38,988 --> 01:18:39,889 THE BLOCKAGE IN THE LIVER. 1753 01:18:39,889 --> 01:18:40,990 SO I'VE SAID IT'S ALMOST ALWAYS 1754 01:18:40,990 --> 01:18:42,191 THE LIVER BUT WHAT IF IT'S THE 1755 01:18:42,191 --> 01:18:43,059 HEART? 1756 01:18:43,059 --> 01:18:47,530 SO HERE'S THE SAME THING I JUST 1757 01:18:47,530 --> 01:18:48,831 SHOWED YOU AND WENT THROUGH WITH 1758 01:18:48,831 --> 01:18:52,101 THE MOST IMPORTANT IN THE BODY, 1759 01:18:52,101 --> 01:18:53,102 BUT WHAT IF THE BLOCKAGE IS 1760 01:18:53,102 --> 01:18:53,769 HERE? 1761 01:18:53,769 --> 01:18:55,771 BACK PRESSURE, THE BLOOD FLUNG 1762 01:18:55,771 --> 01:18:57,006 TO THE HEART, THE LIVER WILL 1763 01:18:57,006 --> 01:19:00,109 BECOME DAMAGED AND LARGE, BACK 1764 01:19:00,109 --> 01:19:01,210 PRESSURE TO THE GUT, BACK 1765 01:19:01,210 --> 01:19:05,381 PRESSURE TO THE SPLEEN. 1766 01:19:05,381 --> 01:19:06,582 NOW BECAUSE THE LIVER IS DAMAGED 1767 01:19:06,582 --> 01:19:11,020 IN ADDITION TO THE HEART, IT'S A 1768 01:19:11,020 --> 01:19:12,888 DOUBLE WHAMMY, THE BLOOD STILL 1769 01:19:12,888 --> 01:19:14,090 HAS TO GET BACK AROUND THE LIVER 1770 01:19:14,090 --> 01:19:15,458 TO THE HEART AND VARICES STILL 1771 01:19:15,458 --> 01:19:18,327 FORM. 1772 01:19:18,327 --> 01:19:19,829 SO YOU STILL HAVE PORTAL 1773 01:19:19,829 --> 01:19:21,864 HYPERTENSION. 1774 01:19:21,864 --> 01:19:26,268 AND THAT BRINGS US TO FALD, OR 1775 01:19:26,268 --> 01:19:27,370 FONTAN ASSOCIATED LIVER DISEASE. 1776 01:19:27,370 --> 01:19:28,471 YOU HAVE TO ASK WHAT'S SO 1777 01:19:28,471 --> 01:19:31,073 SPECIAL ABOUT IT, WHY ARE WE AT 1778 01:19:31,073 --> 01:19:32,675 THE NIH SPENDING TAX DOLLARS 1779 01:19:32,675 --> 01:19:34,510 LOOKING AT A RARE DISEASE? 1780 01:19:34,510 --> 01:19:38,881 FIRST OF ALL I THINK IT COMES TO 1781 01:19:38,881 --> 01:19:40,082 EVERY PATIENT WHO HAS IT, THEY 1782 01:19:40,082 --> 01:19:41,283 DESERVE THE BEST POSSIBLE CARE, 1783 01:19:41,283 --> 01:19:43,019 BUT THERE ARE OTHER THINGS 1784 01:19:43,019 --> 01:19:44,286 BIOLOGICALLY THAT ARE ALSO 1785 01:19:44,286 --> 01:19:45,421 IMPORTANT. 1786 01:19:45,421 --> 01:19:47,490 THERE'S UNIVERSAL PROGRESSION TO 1787 01:19:47,490 --> 01:19:48,257 ADVANCE FIBROSIS AND I'M GOING 1788 01:19:48,257 --> 01:19:49,525 TO TALK ABOUT THAT IN A LITTLE 1789 01:19:49,525 --> 01:19:49,859 BIT. 1790 01:19:49,859 --> 01:19:51,293 THERE'S NO INFLAMMATION, AND 1791 01:19:51,293 --> 01:19:52,628 REMEMBER I TOLD YOU NO MATTER 1792 01:19:52,628 --> 01:19:54,530 WHAT YOU DO TO THE LIVER, IT 1793 01:19:54,530 --> 01:19:57,066 GOES FROM INFLAMMATION TO 1794 01:19:57,066 --> 01:19:58,034 FIBROSIS TO CIRRHOSIS. 1795 01:19:58,034 --> 01:20:00,936 HERE'S AN EXAMPLE, THE ONLY 1796 01:20:00,936 --> 01:20:01,537 EXAMPLE IN LIVER DISEASE WHERE 1797 01:20:01,537 --> 01:20:04,507 YOU GO FROM DAMAGE, WHATEVER 1798 01:20:04,507 --> 01:20:05,541 THAT IS, WHICH WE'LL TALK ABOUT 1799 01:20:05,541 --> 01:20:09,111 IN A MOMENT, BUT NO CELLULAR 1800 01:20:09,111 --> 01:20:10,880 INFLAMMATION, THERE MIGHT BE 1801 01:20:10,880 --> 01:20:11,847 INFLAMMATION ON THE MOLECULAR 1802 01:20:11,847 --> 01:20:12,815 LEVEL, BUT CELLULAR WISE, 1803 01:20:12,815 --> 01:20:13,883 THERE'S NO INFLAMMATION. 1804 01:20:13,883 --> 01:20:18,154 AND THEN TO CIRRHOSIS. 1805 01:20:18,154 --> 01:20:19,355 AND THIS IS A FIELD AND THESE 1806 01:20:19,355 --> 01:20:20,456 ARE PATIENTS WHERE THERE'S A 1807 01:20:20,456 --> 01:20:21,424 DESPERATE NEED FOR UNDERSTANDING 1808 01:20:21,424 --> 01:20:22,291 AND I THINK THAT MAKES IT 1809 01:20:22,291 --> 01:20:26,328 SPECIAL. 1810 01:20:26,328 --> 01:20:27,663 THIS IS FROM PERHAPS ONE OF THE 1811 01:20:27,663 --> 01:20:28,531 BEST OPINION PIECES WRITTEN 1812 01:20:28,531 --> 01:20:30,032 ABOUT IT AND A LOT OF IT IS 1813 01:20:30,032 --> 01:20:32,735 OPINION AND REVIEWS BECAUSE 1814 01:20:32,735 --> 01:20:33,736 THERE'S SO LITTLE PRIMARY DATA 1815 01:20:33,736 --> 01:20:37,006 AND IT'S SUCH A RARE DISEASE. 1816 01:20:37,006 --> 01:20:38,307 IT'S NOT AS COMPLICATED AS IT 1817 01:20:38,307 --> 01:20:39,742 LOOKS AND I'M GOING TO MAKE A 1818 01:20:39,742 --> 01:20:40,342 SIMPLE POINT. 1819 01:20:40,342 --> 01:20:41,310 THIS IS FOR PATIENTS WITHOUT 1820 01:20:41,310 --> 01:20:43,612 EVIDENCE OF LIVER DISEASE AND ON 1821 01:20:43,612 --> 01:20:44,580 THE RIGHT-HAND SIDE, YOUR 1822 01:20:44,580 --> 01:20:45,481 RIGHT-HAND SIDE, EVIDENCE OF 1823 01:20:45,481 --> 01:20:47,917 PATIENTS WITH LIVER DISEASE. 1824 01:20:47,917 --> 01:20:49,819 IN THE FIRST COLUMN, THOSE 1825 01:20:49,819 --> 01:20:51,153 WITHOUT FIBROSIS ON LIVER BIOPSY 1826 01:20:51,153 --> 01:20:52,688 WHICH IS STANDARD 10 YEARS AFTER 1827 01:20:52,688 --> 01:20:56,726 THE FONTAN, AND LOOK, THAT'S 1828 01:20:56,726 --> 01:20:57,226 RARE. 1829 01:20:57,226 --> 01:20:59,862 YOU ALMOST NEVER SEE FIBROSIS. 1830 01:20:59,862 --> 01:21:01,697 WHAT ABOUT PATIENTS WITH MILD TO 1831 01:21:01,697 --> 01:21:02,932 MODERATE FIBROSIS, THEY SHOULD 1832 01:21:02,932 --> 01:21:04,266 SEE A LIVER DOCTOR, HEPATOLOGY 1833 01:21:04,266 --> 01:21:04,967 REFERRAL. 1834 01:21:04,967 --> 01:21:06,368 WHAT ABOUT PATIENTS WITH 1835 01:21:06,368 --> 01:21:07,803 BRIDGING VIE BRO CYST OR 1836 01:21:07,803 --> 01:21:10,039 CIRRHOSIS OR MORE ADVANCED 1837 01:21:10,039 --> 01:21:12,775 FIBROSIS, THEY SHOULD SEE 1838 01:21:12,775 --> 01:21:13,109 HEMATOLOGY. 1839 01:21:13,109 --> 01:21:14,643 PATIENTS WITH ADVANCED LIVER 1840 01:21:14,643 --> 01:21:15,945 DISEASE, THEY SHOULD SEE 1841 01:21:15,945 --> 01:21:16,445 HEPATOLOGY. 1842 01:21:16,445 --> 01:21:18,214 SO IN ESSENCE EVERYBODY WHO'S 1843 01:21:18,214 --> 01:21:21,817 HAD A FON DAN WHO'S 10 YEARS OUT 1844 01:21:21,817 --> 01:21:23,686 SHOULD SEE A LIVER DOCTOR. 1845 01:21:23,686 --> 01:21:24,820 WE DISCUSSED THIS ALREADY. 1846 01:21:24,820 --> 01:21:26,489 YOU GO FROM HEALTHY TO FIBROSIS 1847 01:21:26,489 --> 01:21:29,959 TO CIRRHOSIS TO CARCINOMA, AND 1848 01:21:29,959 --> 01:21:33,929 IT NORMALLY TAKES 20 TO 40 1849 01:21:33,929 --> 01:21:35,831 YEARS, UNLIKE HEPATITIS B, 1850 01:21:35,831 --> 01:21:36,832 HEPATITIS C, A LOT OF 1851 01:21:36,832 --> 01:21:37,700 INFLAMMATION IN THE 20 TO 40 1852 01:21:37,700 --> 01:21:40,369 YEARS. 1853 01:21:40,369 --> 01:21:41,370 WHAT ABOUT FONTAN? 1854 01:21:41,370 --> 01:21:43,239 GOES FROM NORMAL TO CONGESTION 1855 01:21:43,239 --> 01:21:44,106 TO CIRRHOSIS. 1856 01:21:44,106 --> 01:21:46,575 AND WHENEVER YOU SEE LOTS OF 1857 01:21:46,575 --> 01:21:48,744 WAYS, THIS IS FROM A REVIEW FROM 1858 01:21:48,744 --> 01:21:51,847 2019 BUT HASN'T CHANGED, LOOK 1859 01:21:51,847 --> 01:21:52,915 HOW MANY WAY THERE IS ARE TO 1860 01:21:52,915 --> 01:21:53,883 MONITOR THE LIVER DISEASE. 1861 01:21:53,883 --> 01:21:55,284 YOU'VE GOT TO KNOW THAT NONE OF 1862 01:21:55,284 --> 01:21:58,254 THEM WORK. 1863 01:21:58,254 --> 01:22:00,623 THEY'RE SUGGESTING BLOOD, 1864 01:22:00,623 --> 01:22:02,591 ULTRASOUND, MRI, CAT SCAN AND 1865 01:22:02,591 --> 01:22:03,159 BIOPSY. 1866 01:22:03,159 --> 01:22:04,360 THAT'S LOTS OF DIFFERENT WAYS TO 1867 01:22:04,360 --> 01:22:04,994 THINK ABOUT IT. 1868 01:22:04,994 --> 01:22:08,664 AND AGAIN, NO INFLAMMATION, AND 1869 01:22:08,664 --> 01:22:09,899 ALL OF THESE WAYS THAT WE'RE 1870 01:22:09,899 --> 01:22:13,636 TALKING ABOUT WERE VALIDATED IN 1871 01:22:13,636 --> 01:22:14,703 THE SETTING OF LIVER DISEASE 1872 01:22:14,703 --> 01:22:16,071 WHERE THERE IS INFLAMMATION. 1873 01:22:16,071 --> 01:22:17,506 THAT SHOULD ALREADY BE RAISING 1874 01:22:17,506 --> 01:22:22,645 RED FLAGS AND RINGING BELLS. 1875 01:22:22,645 --> 01:22:23,712 LET'S LOOK AT TRADITIONAL 1876 01:22:23,712 --> 01:22:25,247 MARKERS OF LIVER DISEASE. 1877 01:22:25,247 --> 01:22:26,982 THE FIRST FOUR THINGS IN THE BOX 1878 01:22:26,982 --> 01:22:30,452 TO THE THE LEFT OF YOUR SCREEN, 1879 01:22:30,452 --> 01:22:32,521 THOSE ARE -- MARKERS. 1880 01:22:32,521 --> 01:22:40,296 BELOW THAT IS MORE FUNCTIONAL 1881 01:22:40,296 --> 01:22:45,100 TESTS AND MELD XI, MORE GLOBAL 1882 01:22:45,100 --> 01:22:46,936 ASSESSMENT OF PROGNOSIS, AND THE 1883 01:22:46,936 --> 01:22:49,038 REASON IT EXCRETES CLOTTING 1884 01:22:49,038 --> 01:22:50,539 FACTORS IS BECAUSE THESE 1885 01:22:50,539 --> 01:22:51,740 PATIENTS ARE OFTEN ON BLOOD 1886 01:22:51,740 --> 01:22:55,344 THINNERS. 1887 01:22:55,344 --> 01:22:56,879 IF YOU LOOK, THIS IS A LARGE 1888 01:22:56,879 --> 01:22:58,480 SERIES, A BIG STUDY, 16 PATIENTS 1889 01:22:58,480 --> 01:23:01,083 WITH MILD FIBROSIS AND 22 WITH 1890 01:23:01,083 --> 01:23:01,550 SEVERE FIBROSIS. 1891 01:23:01,550 --> 01:23:03,452 IF YOU WANT TO KNOW IF ANY OF 1892 01:23:03,452 --> 01:23:06,422 THESE DISTINGUISHED ANYTHING, 1893 01:23:06,422 --> 01:23:07,756 LOOK, NONE OF THEM APPROACH 1894 01:23:07,756 --> 01:23:10,259 SIGNIFICANCE, NONE OF THEM 1895 01:23:10,259 --> 01:23:11,093 APPROACH STATISTICAL 1896 01:23:11,093 --> 01:23:11,694 SIGNIFICANCE, IN OTHER WORDS, 1897 01:23:11,694 --> 01:23:12,962 NOT ONE OF THESE TESTS INCLUDING 1898 01:23:12,962 --> 01:23:15,364 THE FUNCTIONAL ASSAYS COULD 1899 01:23:15,364 --> 01:23:16,665 DISTINGUISH PATIENTS WITH MILD 1900 01:23:16,665 --> 01:23:21,337 AND SEVERE FIBROSIS. 1901 01:23:21,337 --> 01:23:22,771 OKAY, THAT'S NOT ENCOURAGING. 1902 01:23:22,771 --> 01:23:24,940 WHAT ABOUT NONINVASIVE MEASURES? 1903 01:23:24,940 --> 01:23:29,545 I'M GOING TO SUMMARIZE. 1904 01:23:29,545 --> 01:23:31,046 SCORES WERE ALL VALIDATED IN 1905 01:23:31,046 --> 01:23:31,881 INFLAMMATORY LIVER DISEASE AND 1906 01:23:31,881 --> 01:23:36,051 HAVE NOT BEEN USEFUL AT ALL IN 1907 01:23:36,051 --> 01:23:39,655 FONTAN. 1908 01:23:39,655 --> 01:23:42,391 IMAGING, THE IMAGING IS A LITTLE 1909 01:23:42,391 --> 01:23:43,492 BIT UNIVERSALLY SCARY AND I'M 1910 01:23:43,492 --> 01:23:45,094 GOING TO SHOW YOU THAT, NOT 1911 01:23:45,094 --> 01:23:48,163 USEFUL TO SEPARATE PATIENTS OR 1912 01:23:48,163 --> 01:23:48,731 PROGNOSTICATE. 1913 01:23:48,731 --> 01:23:49,999 A BIG ADVANCE OVER THE LAST 15 1914 01:23:49,999 --> 01:23:54,036 YEARS IN LIVER DISEASE IS 1915 01:23:54,036 --> 01:23:54,904 ELASTOGRAPHY, WHICH MEASURES HOW 1916 01:23:54,904 --> 01:23:57,473 STIFF THE LIVER IS AND ON THE 1917 01:23:57,473 --> 01:23:59,909 RIGHT-HAND SIDE, YOU CAN SEE AN 1918 01:23:59,909 --> 01:24:03,512 EXAMPLE OF A PATIENT WHO HAD A 1919 01:24:03,512 --> 01:24:07,983 NORMAL OF 5.5 AND THAT BLACK 1920 01:24:07,983 --> 01:24:10,286 LINE, THE WHITE DOTTED LINE 1921 01:24:10,286 --> 01:24:11,387 UNDERNEATH IT IS A WAVE THROUGH 1922 01:24:11,387 --> 01:24:12,855 THE LIVER AND BELOW IT IS A 1923 01:24:12,855 --> 01:24:15,391 PATIENT WITH CIRRHOSIS WITH A 1924 01:24:15,391 --> 01:24:23,565 MUCH DIFFERENT WAVE, 19.1. 1925 01:24:23,565 --> 01:24:25,401 IN HEPATITIS C, OR IN HEPATITIS 1926 01:24:25,401 --> 01:24:29,138 B, THE SIEVENESS OF THE LIVER IS 1927 01:24:29,138 --> 01:24:31,540 DIRECTLY PROPORTIONAL AND 1928 01:24:31,540 --> 01:24:32,308 MOTIONLY PROPORTIONAL TO THE 1929 01:24:32,308 --> 01:24:34,576 AMOUNT OF FIBROSUS BUT IN A 1930 01:24:34,576 --> 01:24:36,011 CONGESTED LIVER LIKE FONTAN, THE 1931 01:24:36,011 --> 01:24:37,212 CONGESTION IS SO MUCH MORE 1932 01:24:37,212 --> 01:24:40,683 IMPORTANT THAN THE FIBROSIS THAT 1933 01:24:40,683 --> 01:24:42,418 THIS IS A BETTER MARKER OF 1934 01:24:42,418 --> 01:24:43,319 CONGESTION THAN FIBROSIS. 1935 01:24:43,319 --> 01:24:45,487 THAT WAS FIRST SHOWN IN 2014 BY 1936 01:24:45,487 --> 01:24:46,322 WU. 1937 01:24:46,322 --> 01:24:52,561 SO NOT HELPFUL HERE EITHER. 1938 01:24:52,561 --> 01:24:59,034 WHAT BR INVAS ABOUT INVASIVE ME, 1939 01:24:59,034 --> 01:24:59,768 LIVER BIOPSY? 1940 01:24:59,768 --> 01:25:00,970 LIVER BIOPSY IS RELATIVELY 1941 01:25:00,970 --> 01:25:03,238 SIMPLE TO DO IN A REGULAR 1942 01:25:03,238 --> 01:25:04,640 SETTING, AND ON A PERSONAL 1943 01:25:04,640 --> 01:25:05,975 LEVEL, I THINK COMPLICATION 1944 01:25:05,975 --> 01:25:07,376 RATES HAVE BEEN OVERSTATED AND 1945 01:25:07,376 --> 01:25:09,979 RISK HAS BEEN OVERSTATED FOR 1946 01:25:09,979 --> 01:25:12,047 MOST PATIENTS BUT IN FONTAN, THE 1947 01:25:12,047 --> 01:25:16,418 RISK IS A LITTLE BIT DIFFERENT. 1948 01:25:16,418 --> 01:25:19,288 PATIENTS HAVE TO BE SEDATED, 1949 01:25:19,288 --> 01:25:20,456 IT'S COMPLEX, YOU'LL SEE IN A 1950 01:25:20,456 --> 01:25:21,957 MOMENT HOW WE GO THROUGH IT. 1951 01:25:21,957 --> 01:25:25,361 IT'S NOT TRIVIAL. 1952 01:25:25,361 --> 01:25:26,662 THE BIOPSY IS VERY REVEALING. 1953 01:25:26,662 --> 01:25:27,930 I DON'T WANT YOU TO THINK ABOUT 1954 01:25:27,930 --> 01:25:33,635 THE NUMBERS ON THE RIGHT OF YOUR 1955 01:25:33,635 --> 01:25:34,837 SCREEN BUT YOU CAN SEE 1956 01:25:34,837 --> 01:25:36,271 INCREASING REDNESS, AND THAT 1957 01:25:36,271 --> 01:25:38,240 GOES FROM NORMAL TO CIRRHOTIC. 1958 01:25:38,240 --> 01:25:40,442 AND YOU CAN SEE THAT YOU CAN 1959 01:25:40,442 --> 01:25:41,110 TELL THE DIFFERENCE. 1960 01:25:41,110 --> 01:25:43,979 CAN YOU REALLY SEE THE PATTERN 1961 01:25:43,979 --> 01:25:46,181 OF CIRRHOSIS IS DIFFERENT IN 1962 01:25:46,181 --> 01:25:50,019 PATIENTS WITH CONGESTION BUT THE 1963 01:25:50,019 --> 01:25:52,488 ESSENCE IS THE SAME. 1964 01:25:52,488 --> 01:25:54,023 I JUST WANT TO REINFORCE SOME OF 1965 01:25:54,023 --> 01:25:56,892 WHAT I'VE JUST SAID BY LOOKING 1966 01:25:56,892 --> 01:25:59,028 AT A PATIENT, NOT ANGELICA 1967 01:25:59,028 --> 01:26:03,198 MILLER, A DIFFERENT PATIENT. 1968 01:26:03,198 --> 01:26:04,833 THIS IS THE PATIENT'S BLOOD 1969 01:26:04,833 --> 01:26:05,934 TESTS OVER TIME AT THE NIH AND 1970 01:26:05,934 --> 01:26:11,040 YOU CAN SEE THAT THE MOOD 1971 01:26:11,040 --> 01:26:13,108 MARKERS ARE NORMAL, NOT JUST 1972 01:26:13,108 --> 01:26:16,045 NORMAL BUT LOW 20s. 1973 01:26:16,045 --> 01:26:19,214 LOOK AT 7/9/21, REALLY LOW. 1974 01:26:19,214 --> 01:26:20,849 BILIRUBIN IS ELEVATED BUT THAT'S 1975 01:26:20,849 --> 01:26:25,754 THE ONLY THING AND THE 1976 01:26:25,754 --> 01:26:27,723 PATIENT -- THE GGT WHICH IS 1977 01:26:27,723 --> 01:26:29,024 OFTEN THOUGHT OF AS THE BEST 1978 01:26:29,024 --> 01:26:35,164 MARKER OF CONGESTION, NORMAL IS 1979 01:26:35,164 --> 01:26:40,469 175 175 WHICH IS NORMAL, ALBUMI, 1980 01:26:40,469 --> 01:26:42,771 REMEMBER I SHOWED YOU HOW THE 1981 01:26:42,771 --> 01:26:45,040 SPLEEN GETS BIG, MO PLATELETS 1982 01:26:45,040 --> 01:26:46,675 ARE RECYCLED, NOT THE CASE HERE, 1983 01:26:46,675 --> 01:26:49,044 AND HIS ALBUMEN IS VERY NORMAL 1984 01:26:49,044 --> 01:26:49,845 AT 5. 1985 01:26:49,845 --> 01:26:52,681 THIS IS LIVER BIOPSY IN 2017. 1986 01:26:52,681 --> 01:26:54,550 AND HE CIRRHOSIS. 1987 01:26:54,550 --> 01:26:57,152 THANK DR. KLEINER FOR THIS 1988 01:26:57,152 --> 01:26:58,020 SLIDE. 1989 01:26:58,020 --> 01:27:02,191 AND IF YOU LOOK AT HIS UPPER 1990 01:27:02,191 --> 01:27:08,297 ENDOSCOPY, HE HAS VARICES. 1991 01:27:08,297 --> 01:27:10,199 HERE'S HIS IMAGING, MRI, AND YOU 1992 01:27:10,199 --> 01:27:15,170 CAN SEE THE LIVER LOOKS VEGGIE 1993 01:27:15,170 --> 01:27:16,371 GRAPHIC, IT'S BROKEN UP, THERE'S 1994 01:27:16,371 --> 01:27:18,774 LOTS OF THICK FIBROUS BANDS 1995 01:27:18,774 --> 01:27:22,144 RUNNING ALONG THE PORTAL TRACTS, 1996 01:27:22,144 --> 01:27:23,245 AND PARTICULARLY IN THE RIGHT 1997 01:27:23,245 --> 01:27:24,746 LOBE WHICH IS TO THE LEFT OF 1998 01:27:24,746 --> 01:27:26,181 YOUR SCREEN, IT LOOKS VERY 1999 01:27:26,181 --> 01:27:29,251 FRAGMENTED AND IF WE GIVE 2000 01:27:29,251 --> 01:27:32,387 CONTRAST, THIS IS AN ARTERIAL 2001 01:27:32,387 --> 01:27:35,357 PHASE, YOU CAN SEE THAT RIGHT 2002 01:27:35,357 --> 01:27:36,992 LOBE LOOKS EVEN WORSE. 2003 01:27:36,992 --> 01:27:39,194 AND THE LEFT LOBE IS SMALL AND 2004 01:27:39,194 --> 01:27:44,833 NOT QUITE NORMAL EITHER. 2005 01:27:44,833 --> 01:27:46,034 THIS PATIENT IS DOING WELL, 2006 01:27:46,034 --> 01:27:47,469 WORKS EVERY DAY, HAS CHILDREN, 2007 01:27:47,469 --> 01:27:49,438 IS MARRIED, GOES ABOUT HIS 2008 01:27:49,438 --> 01:27:50,606 REGULAR LIFE AND THE SAME WAY 2009 01:27:50,606 --> 01:27:52,808 THAT YOU HEARD FROM ANGELICA, 2010 01:27:52,808 --> 01:27:54,443 HE'S LIVING HIS LIFE, BUT WITH 2011 01:27:54,443 --> 01:27:55,410 CIRRHOSIS NOW FOR YEARS, I 2012 01:27:55,410 --> 01:27:57,246 SHOWED YOU THE BIOPSY FROM 2017. 2013 01:27:57,246 --> 01:28:03,085 HE'S DOING THE SAME TODAY. 2014 01:28:03,085 --> 01:28:05,254 THIS IS TAKEN FROM THAT PAPER I 2015 01:28:05,254 --> 01:28:09,725 REFERRED TO INITIALLY AND I WANT 2016 01:28:09,725 --> 01:28:12,127 TO READ A QUOTE NOT TO PUT THE 2017 01:28:12,127 --> 01:28:15,631 LIVER BIEBS IN CONTEXT. 2018 01:28:15,631 --> 01:28:17,065 SEVERE FIBROSIS ON A LIVER 2019 01:28:17,065 --> 01:28:19,134 BIOPSY MAY NOT IN AND OF ITSELF 2020 01:28:19,134 --> 01:28:20,769 INDICATE THE NEED OF LIVER 2021 01:28:20,769 --> 01:28:22,204 TRANSPLANT AND I CREASED RISK OF 2022 01:28:22,204 --> 01:28:23,172 LIVER RELATED MORTALITY. 2023 01:28:23,172 --> 01:28:24,373 SO WAIT. 2024 01:28:24,373 --> 01:28:25,874 WE'VE GOT TO BIOPSY THE PATIENT 2025 01:28:25,874 --> 01:28:29,278 AND IT DOESN'T REALLY TELL US 2026 01:28:29,278 --> 01:28:30,045 WHAT'S GOING TO HAPPEN? 2027 01:28:30,045 --> 01:28:31,547 SO IT'S NOT JUST THE BLOOD TESTS 2028 01:28:31,547 --> 01:28:33,315 AND THE NONINVASIVE IMAGING AND 2029 01:28:33,315 --> 01:28:35,050 THE SCORES. 2030 01:28:35,050 --> 01:28:37,352 THE LIVER BIOPSY ITSELF IS NOT 2031 01:28:37,352 --> 01:28:38,120 PREDICTIVE, AS I JUST SHOWED 2032 01:28:38,120 --> 01:28:41,490 YOU. 2033 01:28:41,490 --> 01:28:43,592 BUT THEN THEY STILL GO ON TO SAY 2034 01:28:43,592 --> 01:28:45,093 PATIENTS WITH CLINICAL SIGNS AND 2035 01:28:45,093 --> 01:28:46,595 SYMPTOMS WITH CHRONIC LIVER 2036 01:28:46,595 --> 01:28:47,963 DISEASE SHOULD UNDERGO BIOPSY AT 2037 01:28:47,963 --> 01:28:49,998 10 YEARS POST FONTAN AS 2038 01:28:49,998 --> 01:28:51,166 VIRTUALLY ALL PATIENTS HAVE BEEN 2039 01:28:51,166 --> 01:28:52,935 REPORT TODAY HAVE SOME EVIDENCE 2040 01:28:52,935 --> 01:28:55,904 OF FIBROSIS AND THESE DATA WILL 2041 01:28:55,904 --> 01:28:57,406 FURTHER DIRECT CLINICAL 2042 01:28:57,406 --> 01:28:59,041 MANAGEMENT. 2043 01:28:59,041 --> 01:29:00,342 SO DIFFICULT TO PUT IT TOGETHER 2044 01:29:00,342 --> 01:29:01,343 EVEN IN THE SAME PAPER. 2045 01:29:01,343 --> 01:29:03,545 FOR ME, IT MEANS HEPATOLOGY 2046 01:29:03,545 --> 01:29:04,746 REFERRAL FOR CLOSE FOLLOW-UP. 2047 01:29:04,746 --> 01:29:06,114 THAT'S HOW IT CHANGES CLINICAL 2048 01:29:06,114 --> 01:29:09,418 MANAGEMENT. 2049 01:29:09,418 --> 01:29:10,953 I WANT TO HIGHLIGHT ONE STUDY 2050 01:29:10,953 --> 01:29:15,324 BECAUSE THIS REALLY -- THERE ARE 2051 01:29:15,324 --> 01:29:16,592 OTHER STUDIES THAT SHOW THE SAME 2052 01:29:16,592 --> 01:29:18,093 THING BUT THIS REALLY PUTS IT 2053 01:29:18,093 --> 01:29:18,694 INTO CON TECH. 2054 01:29:18,694 --> 01:29:23,065 THIS ICONTEXT.THIS IS FROM THE L 2055 01:29:23,065 --> 01:29:23,699 AMERICAN HEART ASSOCIATION? 2056 01:29:23,699 --> 01:29:25,434 2023 AND THIS IS THE WHOLE DATA 2057 01:29:25,434 --> 01:29:27,836 SECTION LOOKING AT ALL PATIENTS. 2058 01:29:27,836 --> 01:29:30,005 512 FONTAN PATIENTS. 2059 01:29:30,005 --> 01:29:34,176 IN THE REGISTRY. 2060 01:29:34,176 --> 01:29:37,012 10,232 WITH VEN TRICK COLLAR 2061 01:29:37,012 --> 01:29:38,213 SEPTAL DEFECT WHICH IS A 2062 01:29:38,213 --> 01:29:40,282 DIFFERENT CONGENITAL HEART 2063 01:29:40,282 --> 01:29:40,549 CONDITION. 2064 01:29:40,549 --> 01:29:41,450 SEVERE FONTAN ASSOCIATED LIVER 2065 01:29:41,450 --> 01:29:44,319 DISEASE IN THE FONTAN PATIENTS. 2066 01:29:44,319 --> 01:29:46,888 WAS 12% AT 10 YEARS AND 52% AT 2067 01:29:46,888 --> 01:29:49,992 35 YEARS. 2068 01:29:49,992 --> 01:29:52,060 SEVERE LIVER COMPLICATIONS IN 2069 01:29:52,060 --> 01:29:55,897 THE VST WAS .5 AND .275 2070 01:29:55,897 --> 01:29:57,299 RESPECTIVELY AT 10 AND 35 YEARS. 2071 01:29:57,299 --> 01:29:58,734 SO FONTAN, VERY DIFFERENT, AND 2072 01:29:58,734 --> 01:30:00,269 THE RISK OF FONTAN ASSOCIATED 2073 01:30:00,269 --> 01:30:02,304 LIVER DISEASE SEVERE FONTAN 2074 01:30:02,304 --> 01:30:06,475 ASSOCIATED LIVER DISEASE AT 12% 2075 01:30:06,475 --> 01:30:07,676 AT 10 YEARS IS HIGH. 2076 01:30:07,676 --> 01:30:11,246 AND AT FIVE YEARS, THE 2077 01:30:11,246 --> 01:30:13,782 CUMULATIVE RISK OF DEATH WAS 2078 01:30:13,782 --> 01:30:15,317 12.6% IN SEVERE FONTAN 2079 01:30:15,317 --> 01:30:18,253 ASSOCIATED LIVER DISEASE VERSUS 2080 01:30:18,253 --> 01:30:24,126 3.7% IN FONTAN PATIENTS WITHOUT 2081 01:30:24,126 --> 01:30:25,227 FALD, A MORE THAN THREE FOLD 2082 01:30:25,227 --> 01:30:26,328 INCREASE IN MORTALITY JUST DUE 2083 01:30:26,328 --> 01:30:27,095 TO THE LIVER DISEASE. 2084 01:30:27,095 --> 01:30:29,398 SO THE LIVER DISEASE MATTERS, 2085 01:30:29,398 --> 01:30:31,133 THE LIVER DISEASE INCREASES THE 2086 01:30:31,133 --> 01:30:34,336 RISK OF DEATH FIVE YEARS OUT BY 2087 01:30:34,336 --> 01:30:37,372 THREE FOLD. 2088 01:30:37,372 --> 01:30:38,674 AND THE RISK OF FONTAN 2089 01:30:38,674 --> 01:30:39,875 ASSOCIATED LIVER DISEASE IS TIME 2090 01:30:39,875 --> 01:30:41,576 DEPENDENT AND CAN REACH 50% BY 2091 01:30:41,576 --> 01:30:46,014 35 YEARS. 2092 01:30:46,014 --> 01:30:47,649 JUST TO TALK A LITTLE ABOUT 2093 01:30:47,649 --> 01:30:48,550 MANAGEMENT, NOT BECAUSE I REALLY 2094 01:30:48,550 --> 01:30:49,885 WANT TO GO THROUGH IT BUT JUST 2095 01:30:49,885 --> 01:30:52,754 TO SHOW YOU THAT IT'S COMPLEX, 2096 01:30:52,754 --> 01:30:57,426 AND IN ITSELF SIGNIFICANT, TWO 2097 01:30:57,426 --> 01:30:58,660 OPTIONS WITH A FAILING FONTAN 2098 01:30:58,660 --> 01:31:00,195 AND FONTAN ASSOCIATED LIVER 2099 01:31:00,195 --> 01:31:00,962 DISEASE. 2100 01:31:00,962 --> 01:31:02,364 HEART TRANSPLANT ALONE IF YOU 2101 01:31:02,364 --> 01:31:04,900 LOOK IN THE UPPER RIGHT, AND 2102 01:31:04,900 --> 01:31:06,501 THEY CAN REGRESS FIBROSIS AND 2103 01:31:06,501 --> 01:31:07,936 THIS IS ONE OF THE MOST EXCITING 2104 01:31:07,936 --> 01:31:11,340 THINGS ABOUT LIVER DISEASE. 2105 01:31:11,340 --> 01:31:14,009 IS THAT FIBROSIS CAN REGRESS AND 2106 01:31:14,009 --> 01:31:23,985 EVEN CIRRHOSIS CAN REGRESS. 2107 01:31:23,985 --> 01:31:24,786 OR PATIENTS CAN STILL CONTINUE 2108 01:31:24,786 --> 01:31:26,188 TO CIRRHOSIS OR DECOMPENSATE 2109 01:31:26,188 --> 01:31:32,194 EVEN WITH A NEW HEART AND EVEN 2110 01:31:32,194 --> 01:31:37,566 WITHOUT PROGRESSION THEY CAN 2111 01:31:37,566 --> 01:31:45,073 DEVELOP H HEPATITIS CARCINOMA. 2112 01:31:45,073 --> 01:31:46,408 THIS IS SORT OF REALLY TAKING 2113 01:31:46,408 --> 01:31:47,542 OFF NOW WHERE THE LIVER PROTECTS 2114 01:31:47,542 --> 01:31:49,478 THE HEART, THERE'S FAR LESS 2115 01:31:49,478 --> 01:31:52,848 REJECTION AND THAT'S BECAUSE THE 2116 01:31:52,848 --> 01:31:53,949 LIVER -- ONE OF THE LIVER'S 2117 01:31:53,949 --> 01:31:54,950 MAJOR FUNCTIONS WHICH I DIDN'T 2118 01:31:54,950 --> 01:31:56,685 TALK ABOUT IS THAT IT'S IMMUNE 2119 01:31:56,685 --> 01:31:57,886 CENTRAL AND IT INDUCES 2120 01:31:57,886 --> 01:32:02,257 TOLERANCE. 2121 01:32:02,257 --> 01:32:06,628 THIS IS CANCER RISK, DESCRIBED 2122 01:32:06,628 --> 01:32:07,929 IN TEENAGERS WITH FONTAN 2123 01:32:07,929 --> 01:32:08,930 ASSOCIATED LIVER DISEASE AND HOW 2124 01:32:08,930 --> 01:32:10,365 TO SCREEN IS COMPLETELY UNKNOWN. 2125 01:32:10,365 --> 01:32:12,768 MORE THAN THAT, THE GUIDELINES 2126 01:32:12,768 --> 01:32:18,407 IF I CAN COMMENT -- THE CRITERIA 2127 01:32:18,407 --> 01:32:21,042 WE USE TO ASSESS WHETHER OR NOT 2128 01:32:21,042 --> 01:32:23,678 SOMEONE HAS LIVER CANCER ON 2129 01:32:23,678 --> 01:32:25,414 IMAGING, CAT SCAN OR MRI, WAS 2130 01:32:25,414 --> 01:32:28,417 ALL DEVELOPED IN HEPATITIS C AND 2131 01:32:28,417 --> 01:32:29,551 HEPATITIS B IN INFLAMMATORY 2132 01:32:29,551 --> 01:32:30,318 LIVER DISEASE. 2133 01:32:30,318 --> 01:32:33,488 NOT RELEVANT HERE. 2134 01:32:33,488 --> 01:32:34,923 BUT IT'S BASED ON WHETHER 2135 01:32:34,923 --> 01:32:38,393 THERE'S ARTERIAL ENHANCEMENT OR 2136 01:32:38,393 --> 01:32:39,828 NOT AND WHETHER THERE'S WASHOUT 2137 01:32:39,828 --> 01:32:43,231 IN THE PORTAL VENOUS PHASE OF 2138 01:32:43,231 --> 01:32:45,500 THE IMAGING. 2139 01:32:45,500 --> 01:32:47,369 BUT REMEMBER THE LIVER GETS 2140 01:32:47,369 --> 01:32:48,670 NONPULSATILE FLOW, AND THE LIVER 2141 01:32:48,670 --> 01:32:50,205 IS CONGESTED. 2142 01:32:50,205 --> 01:32:52,374 SO THE WASHOUT AND ARTERIAL 2143 01:32:52,374 --> 01:32:54,342 PHASE DO NOT LOOK THE SAME AS IN 2144 01:32:54,342 --> 01:32:56,411 REGULAR CANCER. 2145 01:32:56,411 --> 01:32:59,815 SO THE CRITERIA DON'T APPLY 2146 01:32:59,815 --> 01:33:00,682 HERE, AND PATIENTS WITH FONTAN 2147 01:33:00,682 --> 01:33:04,286 HAVE A LOT OF BENIGN LESIONS, 2148 01:33:04,286 --> 01:33:08,223 LOT OF LIVER NODULES, INCREASING 2149 01:33:08,223 --> 01:33:08,957 COMPLEXITY, AND DIFFICULTY IN 2150 01:33:08,957 --> 01:33:10,926 SCREENING. 2151 01:33:10,926 --> 01:33:14,896 SO THIS IS FRUSTRATING, STANDARD 2152 01:33:14,896 --> 01:33:16,298 TESTS DON'T HELP, STANDARD TESTS 2153 01:33:16,298 --> 01:33:21,636 DON'T APPLY, STANDARD GUIDELINES 2154 01:33:21,636 --> 01:33:25,173 DON'T DIAGNOSE OR MANAGE. 2155 01:33:25,173 --> 01:33:27,342 NOT SO SIMPLE. 2156 01:33:27,342 --> 01:33:31,379 AND ANYWAY, WHY DID THIS GO ON, 2157 01:33:31,379 --> 01:33:33,348 WHY IS THERE PROGRESSION, 2158 01:33:33,348 --> 01:33:34,883 DECOMPOSITION AND CANCER, AND 2159 01:33:34,883 --> 01:33:36,852 WHY DOESN'T IT ALL PREDICT WHAT 2160 01:33:36,852 --> 01:33:37,819 IT SHOULD? 2161 01:33:37,819 --> 01:33:40,789 HOW SHOULD PATIENTS BE 2162 01:33:40,789 --> 01:33:41,556 MONITORED, WHAT SHOULD BE 2163 01:33:41,556 --> 01:33:42,991 MONITOR AND HOW DO WE PREDICT 2164 01:33:42,991 --> 01:33:44,392 WHO'S GOING TO NEED INTERVENTION 2165 01:33:44,392 --> 01:33:49,965 AND WHO DOESN'T? 2166 01:33:49,965 --> 01:33:51,500 WE CAN'T STUDY OR UNDERSTAND IF 2167 01:33:51,500 --> 01:33:52,601 WE CAN'T MEASURE OR EVEN KNOW 2168 01:33:52,601 --> 01:33:55,437 WHAT TO MEASURE. 2169 01:33:55,437 --> 01:33:58,373 IT'S VERY TRU FRUSTRATING. 2170 01:33:58,373 --> 01:34:00,141 I HOPE YOU FEEL MY FRUSTRATION. 2171 01:34:00,141 --> 01:34:03,111 SO MUCH CONFUSION. 2172 01:34:03,111 --> 01:34:06,581 SO IN TRUE NIH FASHION, WHEN 2173 01:34:06,581 --> 01:34:07,883 THERE'S CONFUSION AND WHEN 2174 01:34:07,883 --> 01:34:08,717 THERE'S CONSTERNATION, WE GO 2175 01:34:08,717 --> 01:34:09,651 BACK TO THE BASIC. 2176 01:34:09,651 --> 01:34:11,186 WE WRITE A PROTOCOL. 2177 01:34:11,186 --> 01:34:13,722 WE SAY WHAT IS IT THAT WE KNOW, 2178 01:34:13,722 --> 01:34:16,758 WHAT DO WE KNOW TO BE TRUE, AND 2179 01:34:16,758 --> 01:34:20,161 HOW CAN WE BUILD ON THAT? 2180 01:34:20,161 --> 01:34:22,464 SO THIS IS WHAT WE KNOW TO BE 2181 01:34:22,464 --> 01:34:22,898 TRUE. 2182 01:34:22,898 --> 01:34:26,401 IT'S A DIFFERENT WAY OF SHOWING 2183 01:34:26,401 --> 01:34:27,502 THE CIRCULATION. 2184 01:34:27,502 --> 01:34:28,904 HERE IS THE HEART, I HOPE YOU 2185 01:34:28,904 --> 01:34:30,438 CAN SEE THE MOUSE, THERE'S FLOW 2186 01:34:30,438 --> 01:34:32,507 FROM THE HEART TO THE LIVER AND 2187 01:34:32,507 --> 01:34:34,376 THE GUT, AND WHAT I WANT TO 2188 01:34:34,376 --> 01:34:35,577 EMPHASIZE IS THAT THERE'S A 2189 01:34:35,577 --> 01:34:37,345 CAPILLARY BED IN THE GUT WHICH 2190 01:34:37,345 --> 01:34:40,849 REMOVES MOST OF THE OXYGEN, THE 2191 01:34:40,849 --> 01:34:43,018 PORTAL BLOOD FLOWS TO THE HEART. 2192 01:34:43,018 --> 01:34:45,654 THERE'S ANOTHER CAPILLARY BED IN 2193 01:34:45,654 --> 01:34:46,855 THE SINUS -- WHICH I'M GOING TO 2194 01:34:46,855 --> 01:34:49,124 SHOW YOU AND THEN THE BLOOD 2195 01:34:49,124 --> 01:34:52,427 FLOWS PA PASSIVELY TO THE LUNGS 2196 01:34:52,427 --> 01:34:54,596 WHERE THE BLOOD GETS OXYGENATED 2197 01:34:54,596 --> 01:34:56,598 AND THEN GOES BACK TO THE HEART. 2198 01:34:56,598 --> 01:34:58,333 SO THREE CAPILLARY BEDS WITH 2199 01:34:58,333 --> 01:35:01,069 PASSIVE FLOW. 2200 01:35:01,069 --> 01:35:03,471 IF WE TAKE THE LIVER AND THE 2201 01:35:03,471 --> 01:35:04,439 SINUSOIDS AND BREAK THAT DOWN, 2202 01:35:04,439 --> 01:35:06,274 IF YOU FOCUS ON THE RIGHT, IN 2203 01:35:06,274 --> 01:35:09,377 THE BLUE HERE IS A VEIN, AND IN 2204 01:35:09,377 --> 01:35:14,416 THE RED IS THE ARTERY, AND THESE 2205 01:35:14,416 --> 01:35:16,718 MIX IN THE SINUSOIDS AND THE 2206 01:35:16,718 --> 01:35:17,919 PLATES ARE ILLUSTRATED HERE AND 2207 01:35:17,919 --> 01:35:19,888 FLOW BACK TO THE CENTRAL VEIN. 2208 01:35:19,888 --> 01:35:21,456 HERE'S A HISTOLOGICAL PICTURE OF 2209 01:35:21,456 --> 01:35:23,191 THAT. 2210 01:35:23,191 --> 01:35:25,927 ON THE RIGHT HERE, THERE'S A 2211 01:35:25,927 --> 01:35:27,329 SMALL BRANCH OF THE HEPATIC 2212 01:35:27,329 --> 01:35:28,663 ARTERY, A LARGE CENTRAL WHICH IS 2213 01:35:28,663 --> 01:35:30,165 TYPICAL PORTAL VEIN AND NEXT TO 2214 01:35:30,165 --> 01:35:38,707 THAT, A BILE DUCT. 2215 01:35:38,707 --> 01:35:40,575 ONE MORE LEVEL IF WE LOOK A 2216 01:35:40,575 --> 01:35:43,311 LITTLE BIT DEEPER IN A DIFFERENT 2217 01:35:43,311 --> 01:35:44,512 FORMAT, HERE'S THE PORTAL VEIN 2218 01:35:44,512 --> 01:35:47,148 ON THE LEFT WITH THE HEPATIC 2219 01:35:47,148 --> 01:35:49,351 ARTERIOLE AND THE BLOOD FLOWING 2220 01:35:49,351 --> 01:35:52,387 THROUGH THE SINUSOID TO THE 2221 01:35:52,387 --> 01:35:54,055 TERMINAL HEPATIC VEINS, AND THE 2222 01:35:54,055 --> 01:35:58,293 SPACE BETWEEN THE ENDOTHELIUM 2223 01:35:58,293 --> 01:36:00,695 AND THE -- IS THE SPACE OF THIS, 2224 01:36:00,695 --> 01:36:02,897 AND THIS IS FILLED WITH FLUID, 2225 01:36:02,897 --> 01:36:07,602 AND AS THIS PULSATILE FLOAL IN 2226 01:36:07,602 --> 01:36:12,073 THE -- IN THIS SINUSOID, THERE'S 2227 01:36:12,073 --> 01:36:14,943 COUNTERFLOW AND REVERSE FLOW IN 2228 01:36:14,943 --> 01:36:17,112 THE SPACE OF THIS HERE WHICH 2229 01:36:17,112 --> 01:36:18,947 BECOMES THE LYMPHATICS AND FLOWS 2230 01:36:18,947 --> 01:36:23,018 INTO THE SPACE OF -- WHICH 2231 01:36:23,018 --> 01:36:24,519 SURROUNDS THE PORTAL VEIN AND 2232 01:36:24,519 --> 01:36:27,522 THE ARTERY HERE. 2233 01:36:27,522 --> 01:36:31,026 SO AS THE PULSATILE FLOW COMES 2234 01:36:31,026 --> 01:36:33,428 IN, THE COUNTERFLOW IN THE SPACE 2235 01:36:33,428 --> 01:36:36,297 OF THIS OCCURS AND FORMS 2236 01:36:36,297 --> 01:36:37,165 LYMPHATIC FLOW OUTSIDE OF THE 2237 01:36:37,165 --> 01:36:39,334 LIVER WHICH GOES DOWN TO THE 2238 01:36:39,334 --> 01:36:43,972 PORTAL TRACTS TO THE PORTAL 2239 01:36:43,972 --> 01:36:45,940 HEPATIS, AND 70% OF THE 2240 01:36:45,940 --> 01:36:46,708 INTRAABDOMINAL LISM ACTUALLY 2241 01:36:46,708 --> 01:36:47,609 COMES FROM THE LIVER. 2242 01:36:47,609 --> 01:36:49,878 AS THE LIVER FIBROSES, THIS IS 2243 01:36:49,878 --> 01:36:50,979 ALL ALTERED AND MADE MORE 2244 01:36:50,979 --> 01:36:53,014 DIFFICULT. 2245 01:36:53,014 --> 01:36:54,783 BUT LET'S THINK ABOUT IT. 2246 01:36:54,783 --> 01:36:57,852 ARE SO WHAT WE DO KNOW IS THERE 2247 01:36:57,852 --> 01:36:59,020 ARE MULTIPLE PROCESSES. 2248 01:36:59,020 --> 01:37:01,556 THE PORTAL PRESSURE ITSELF IS 2249 01:37:01,556 --> 01:37:03,191 HIGH, BOTH BECAUSE THERE'S 2250 01:37:03,191 --> 01:37:04,726 OUTFLOW PROBLEMS AND BECAUSE 2251 01:37:04,726 --> 01:37:06,828 THERE'S DECREASED CARDIAC OUTPUT 2252 01:37:06,828 --> 01:37:08,997 OR INFLOW PROBLEMS. 2253 01:37:08,997 --> 01:37:10,865 WHEN THE PORTAL PRESSURE GOES 2254 01:37:10,865 --> 01:37:12,167 ABOVE 20 WHICH IS VERY 2255 01:37:12,167 --> 01:37:14,903 DIFFICULT, THERE'S LOSS OF 2256 01:37:14,903 --> 01:37:16,337 ARTERIAL BUFFERING. 2257 01:37:16,337 --> 01:37:18,106 THE ARTERY CAN BUFFER AND ADAPT 2258 01:37:18,106 --> 01:37:19,407 TO THAT BUT IT CAN'T ONCE THE 2259 01:37:19,407 --> 01:37:20,809 PRESSURE EXCEEDS A CERTAIN 2260 01:37:20,809 --> 01:37:21,376 AMOUNT. 2261 01:37:21,376 --> 01:37:23,545 THERE'S HYPOXIA, THE LYMPHATICS 2262 01:37:23,545 --> 01:37:26,181 ARE IMPAIRED, AS THERE'S LOSS OF 2263 01:37:26,181 --> 01:37:28,583 PULL TILE FLOW, THERE'S CHRONIC 2264 01:37:28,583 --> 01:37:29,784 CONGESTION AND THERE'S SHEAR 2265 01:37:29,784 --> 01:37:31,986 STRESS, ALL OF WHICH DAMAGE THE 2266 01:37:31,986 --> 01:37:33,722 LIVER. 2267 01:37:33,722 --> 01:37:35,023 AND WE KNOW FROM MULTIPLE 2268 01:37:35,023 --> 01:37:36,024 STUDIES THAT TIME IS MORE 2269 01:37:36,024 --> 01:37:37,659 IMPORTANT THAN FONTAN 2270 01:37:37,659 --> 01:37:38,960 CIRCULATION. 2271 01:37:38,960 --> 01:37:41,329 WE FOLLOW ABOUT 100 PATIENTS AT 2272 01:37:41,329 --> 01:37:42,931 THE NIH. 2273 01:37:42,931 --> 01:37:44,566 THERE'S AN EXTREMELY LARGE 2274 01:37:44,566 --> 01:37:47,602 COHORT AND IT'S THANKS TO THE 2275 01:37:47,602 --> 01:37:48,703 REFERRAL CENTER -- AND WE 2276 01:37:48,703 --> 01:37:53,742 DECIDED TO WRITE A PROTOCOL 2277 01:37:53,742 --> 01:37:55,376 WHERE WE WENT BACK TO THE BASICS 2278 01:37:55,376 --> 01:37:58,113 AND FOCUSED ON THE FUNDAMENTALS. 2279 01:37:58,113 --> 01:38:00,014 IT'S WRITTEN FOR UP TO 100 2280 01:38:00,014 --> 01:38:01,382 PATIENTS, LIVER BIOPSY, BLOOD, 2281 01:38:01,382 --> 01:38:02,817 STOOL, PRESSURES, CLINICAL 2282 01:38:02,817 --> 01:38:05,620 PRESSURE AND TO INTEGRATE ALL OF 2283 01:38:05,620 --> 01:38:05,820 THIS. 2284 01:38:05,820 --> 01:38:08,089 THERE'S NO BENEFIT TO THE 2285 01:38:08,089 --> 01:38:08,623 PATIENTS. 2286 01:38:08,623 --> 01:38:09,057 YOUR BENEFIT. 2287 01:38:09,057 --> 01:38:10,592 SO THINK ABOUT SOMEONE LIKE 2288 01:38:10,592 --> 01:38:12,327 ANGELICA, WHO'S BEEN THROUGH SO 2289 01:38:12,327 --> 01:38:15,396 MANY PROCEDURES AND SO MANY -- 2290 01:38:15,396 --> 01:38:16,698 TALK ABOUT THE MEDICAL 2291 01:38:16,698 --> 01:38:19,000 INDUSTRIAL COMPLEX AND SHE 2292 01:38:19,000 --> 01:38:20,869 VOLUNTEERS TO COME IN, TAKE RISK 2293 01:38:20,869 --> 01:38:23,271 TO CONTRIBUTE TO A STUDY LIKE 2294 01:38:23,271 --> 01:38:25,907 THIS WITHOUT ANY BENEFIT TO HER, 2295 01:38:25,907 --> 01:38:27,542 SO WE CAN UNDERSTAND THE DISEASE 2296 01:38:27,542 --> 01:38:29,077 BETTER. 2297 01:38:29,077 --> 01:38:30,178 PRIMARY END POINTS ARE 2298 01:38:30,178 --> 01:38:32,347 IDENTIFICATION OF NOVEL 2299 01:38:32,347 --> 01:38:33,348 BIOMARKERS. 2300 01:38:33,348 --> 01:38:34,883 WE EXPLAINED HER DIFFICULTY TO 2301 01:38:34,883 --> 01:38:35,984 MEASURE THINGS SO WE WANT TO BE 2302 01:38:35,984 --> 01:38:38,720 ABLE TO MEASURE THE DISEASE AND 2303 01:38:38,720 --> 01:38:41,456 LOOK AT THINGS WITH DISEASE 2304 01:38:41,456 --> 01:38:42,557 PROGRESSION AND WE WANT TO 2305 01:38:42,557 --> 01:38:43,291 UNDERSTAND BITOLOGY. 2306 01:38:43,291 --> 01:38:44,626 BECAUSE IF WE CAN UNDERSTAND THE 2307 01:38:44,626 --> 01:38:45,927 BIOLOGY, WE CAN DEVELOP 2308 01:38:45,927 --> 01:38:49,430 THERAPEUTIC INTERVENTIONS. 2309 01:38:49,430 --> 01:38:51,633 SO AS A SIDE, WHY DO WE SCAR? 2310 01:38:51,633 --> 01:38:53,268 IT'S NOT AS SIMPLE AS 2311 01:38:53,268 --> 01:38:54,269 INFLAMMATION. 2312 01:38:54,269 --> 01:38:54,903 THE IMPLICATIONS BEYOND THE 2313 01:38:54,903 --> 01:38:57,872 LIVER. 2314 01:38:57,872 --> 01:38:58,973 THAT'S JUST TO SHOW YOU AN 2315 01:38:58,973 --> 01:39:00,475 EXAMPLE OF HOW LOOKING AT A VERY 2316 01:39:00,475 --> 01:39:04,979 RARE DISEASE, UNDERSTANDING RARE 2317 01:39:04,979 --> 01:39:06,514 BIOLOGY MIGHT HAVE IMPLICATIONS 2318 01:39:06,514 --> 01:39:07,582 BEYOND THAT. 2319 01:39:07,582 --> 01:39:10,652 AND I'LL POINT OUT THAT IT TAKES 2320 01:39:10,652 --> 01:39:10,985 LOVE. 2321 01:39:10,985 --> 01:39:12,620 YOU HAVE TO LOVE WHAT YOU DO. 2322 01:39:12,620 --> 01:39:14,923 IT TAKES CURIOSITY, FOCUS, AND 2323 01:39:14,923 --> 01:39:19,294 SO MANY PEOPLE AND PATIENTS, 2324 01:39:19,294 --> 01:39:21,262 PATIENTS ARE WILLING TO 2325 01:39:21,262 --> 01:39:22,697 VOLUNTEER AND DEDICATE THEIR 2326 01:39:22,697 --> 01:39:23,031 TIME. 2327 01:39:23,031 --> 01:39:25,767 ON THE LEFT-HAND SIDE, PREVIOUS 2328 01:39:25,767 --> 01:39:29,737 JUST FELLOWS HAVE BEEN INVOLVED 2329 01:39:29,737 --> 01:39:33,641 IN THE PROTOCOL, NURSES. 2330 01:39:33,641 --> 01:39:40,849 THE CHILDREN'S TEAM IN GREEN, 2331 01:39:40,849 --> 01:39:49,390 THE HOPKINS TEAM AND THE FAIRFAX 2332 01:39:49,390 --> 01:39:49,724 TEAM. 2333 01:39:49,724 --> 01:39:51,459 AT THE NIH, NOT POSSIBLE TO DO 2334 01:39:51,459 --> 01:39:54,329 ANY OF THIS WITHOUT DR. TOM 2335 01:39:54,329 --> 01:39:55,997 BURKLOW AND PREVIOUSLY DR. DOUG 2336 01:39:55,997 --> 01:39:56,731 ROSEN. 2337 01:39:56,731 --> 01:39:57,799 INCREDIBLE PARTNERS. 2338 01:39:57,799 --> 01:39:59,767 DR. ELLIOTT LEVY, A HIGHLY 2339 01:39:59,767 --> 01:40:01,636 SKILLED TALENTED INTERVENTIONAL 2340 01:40:01,636 --> 01:40:02,604 RADIOLOGIST WHO DOES THE 2341 01:40:02,604 --> 01:40:03,371 PROCEDURE. 2342 01:40:03,371 --> 01:40:07,208 DR. JULIE LEBOSKY WHO GIVES 2343 01:40:07,208 --> 01:40:08,209 SUPERB ANESTHESIA AND MAKES SURE 2344 01:40:08,209 --> 01:40:12,013 THE PATIENTS ARE SAFE, THE 2345 01:40:12,013 --> 01:40:14,349 ENTIRE TEAM. 2346 01:40:14,349 --> 01:40:17,051 AND BECAUSE IT'S COMPLEX, WE 2347 01:40:17,051 --> 01:40:18,486 HAVE REGULAR MEETINGS WITH THE 2348 01:40:18,486 --> 01:40:20,255 REFERRING TEAMS AND THIS IS WHEN 2349 01:40:20,255 --> 01:40:21,656 WE WERE ALLOWED TO DO ZOOM, THIS 2350 01:40:21,656 --> 01:40:23,958 WAS A ZOOM MEETING WITH THE 2351 01:40:23,958 --> 01:40:25,159 REFERRING TEAM. 2352 01:40:25,159 --> 01:40:26,527 DR. JOHN IS HERE SECOND FROM THE 2353 01:40:26,527 --> 01:40:27,262 BOTTOM. 2354 01:40:27,262 --> 01:40:29,330 AND THIS IS A STANDARD SLIDE 2355 01:40:29,330 --> 01:40:31,432 THAT WE MAKE WITH ALL THE DATA 2356 01:40:31,432 --> 01:40:32,600 FROM THE PATIENT, WHERE WE 2357 01:40:32,600 --> 01:40:35,136 PRESENT THAT DATA TO THE 2358 01:40:35,136 --> 01:40:36,771 REFERRING TEAM AND WE DISCUSS 2359 01:40:36,771 --> 01:40:37,772 MANAGEMENT AND MANAGEMENT 2360 01:40:37,772 --> 01:40:40,174 CHANGES, AND WE DO THIS 2361 01:40:40,174 --> 01:40:41,376 REGULARLY, WITH ALL OF THE 2362 01:40:41,376 --> 01:40:42,477 REFERRAL TEAMS TO KEEP THEM IN 2363 01:40:42,477 --> 01:40:43,578 THE LOOP AND MAKE SURE THAT 2364 01:40:43,578 --> 01:40:46,314 PATIENTS ARE GETTING THE BEST 2365 01:40:46,314 --> 01:40:51,552 MULTI-DISCIPLINARY CARE. 2366 01:40:51,552 --> 01:40:52,220 THIS IS THE CURRENT TEAM. 2367 01:40:52,220 --> 01:40:54,088 I WANT TO START WITH THE 2368 01:40:54,088 --> 01:40:58,693 RESEARCH NURSES. 2369 01:40:58,693 --> 01:41:01,763 IN THE CENTER IS CURRENTLY THE 2370 01:41:01,763 --> 01:41:02,730 RESEARCH NURSE RUNNING THE PRO 2371 01:41:02,730 --> 01:41:03,064 KOL. 2372 01:41:03,064 --> 01:41:04,265 BUT ALL OF THE NURSES. 2373 01:41:04,265 --> 01:41:06,935 THE GI FELLOWS WHO DO THE 2374 01:41:06,935 --> 01:41:15,543 ENDOSCOPY, THE LIVER FELLOWS AND 2375 01:41:15,543 --> 01:41:17,178 THE PEOPLE IN MY WORK GROUP, IN 2376 01:41:17,178 --> 01:41:19,714 THE LAB WHO ARE PERFORMING 2377 01:41:19,714 --> 01:41:21,916 INCREDIBLE THINGS, 3D ELECTRON 2378 01:41:21,916 --> 01:41:26,187 MICROSCOPY, LEK CON MICROSCOPY, 2379 01:41:26,187 --> 01:41:30,892 SAMPLES OBTAINED AND HERE IN 2380 01:41:30,892 --> 01:41:32,427 FRONT IS THE PERSON SPEARHEADING 2381 01:41:32,427 --> 01:41:33,528 THIS IN THE LAB. 2382 01:41:33,528 --> 01:41:35,163 AND HERE IN THE FRONT AS WELL IN 2383 01:41:35,163 --> 01:41:40,768 THE RED TOP. 2384 01:41:40,768 --> 01:41:41,836 WITH THAT, I'LL STOP AND THANK 2385 01:41:41,836 --> 01:41:43,404 YOU ALL FOR YOUR ATTENTION AND I 2386 01:41:43,404 --> 01:41:44,806 HOPE THIS WAS ENLIGHTENING, AND 2387 01:41:44,806 --> 01:41:46,574 AGAIN, THANK YOU TO ALL, 2388 01:41:46,574 --> 01:41:48,209 EVERYONE WHO'S BEEN PART OF THE 2389 01:41:48,209 --> 01:41:50,411 STUDY IN ANY WAY. 2390 01:41:50,411 --> 01:41:55,917 >> WELL, THANK YOU BOTH FOR 2391 01:41:55,917 --> 01:42:01,155 REALLY EXCITING INFORMATION, 2392 01:42:01,155 --> 01:42:03,224 EXCITEMENT, AND MOST 2393 01:42:03,224 --> 01:42:05,460 IMPORTANTLY, HOW THE GROUP'S 2394 01:42:05,460 --> 01:42:08,496 HIHYPOTHESIS IS ILLUSTRATED BY 2395 01:42:08,496 --> 01:42:12,100 TODAY'S BRIDGING EXPERIMENT. 2396 01:42:12,100 --> 01:42:14,102 PROBLEMS WORTHY OF ATTACK PROVE 2397 01:42:14,102 --> 01:42:15,937 THEIR WORTH BY STRIKING BACK, 2398 01:42:15,937 --> 01:42:20,775 BUT CREATING IMPORTANT ISSUES AS 2399 01:42:20,775 --> 01:42:25,713 THEO POINTS OUT, THAT EVEN WHERE 2400 01:42:25,713 --> 01:42:30,418 THE WEAR DISEASE BECOMES THE 2401 01:42:30,418 --> 01:42:32,053 STIMULUS FOR UNDERSTANDING 2402 01:42:32,053 --> 01:42:34,689 MECHANISMS THAT OCCUR IN OTHER 2403 01:42:34,689 --> 01:42:37,058 FORMS OF LIVER DISEASE THAT ARE 2404 01:42:37,058 --> 01:42:37,892 FAR MORE COMMON. 2405 01:42:37,892 --> 01:42:41,729 NOW WE HAVE A SERIES OF 2406 01:42:41,729 --> 01:42:43,564 QUESTIONS, AND, WELL, LET'S SEE, 2407 01:42:43,564 --> 01:42:46,467 HERE'S ONE THAT JUST CAME IN. 2408 01:42:46,467 --> 01:42:49,103 ARE CONGENITAL HEART DISEASE 2409 01:42:49,103 --> 01:42:56,110 PATIENTS SUITABLE AND ELIGIBLE 2410 01:42:56,110 --> 01:42:57,745 FOR LIVER TRANSPLANTS, AND IF 2411 01:42:57,745 --> 01:42:58,746 SO, WHAT PRIORITY LEVELS ARE 2412 01:42:58,746 --> 01:43:05,953 THEY GIVEN, AND ARE THERE KIND 2413 01:43:05,953 --> 01:43:10,324 OF SPECIFIC LIMITS AT WHICH A 2414 01:43:10,324 --> 01:43:13,394 TRANSPLANT IS DEEMED NECESSARY? 2415 01:43:13,394 --> 01:43:15,263 SO PERHAPS THEO YOU WANT TO 2416 01:43:15,263 --> 01:43:19,767 ANSWER THAT ONE. 2417 01:43:19,767 --> 01:43:21,602 >> I'LL FIRST REFER SPECIFICALLY 2418 01:43:21,602 --> 01:43:22,770 TO FONTAN ASSOCIATED LIVER 2419 01:43:22,770 --> 01:43:24,272 DISEASE. 2420 01:43:24,272 --> 01:43:25,773 PEOPLE HAVE DONE LIVER 2421 01:43:25,773 --> 01:43:26,874 TRANSPLANTS BUT UNLESS YOU FIX 2422 01:43:26,874 --> 01:43:29,277 THE HEART, THE SAME THING 2423 01:43:29,277 --> 01:43:32,713 HAPPENS AGAIN. 2424 01:43:32,713 --> 01:43:34,115 AND IN THE MORE IMMEDIATE SENSE, 2425 01:43:34,115 --> 01:43:35,216 IT'S VERY DIFFICULT TO GET 2426 01:43:35,216 --> 01:43:37,919 PATIENTS WITH A FAILING FONTAN 2427 01:43:37,919 --> 01:43:39,220 OR SUBOPTIMAL CARDIAC FUNCTION 2428 01:43:39,220 --> 01:43:41,556 THROUGH A LIVE TRANSPLANT. 2429 01:43:41,556 --> 01:43:42,990 SO PEOPLE HAVE NOT BEEN DOING 2430 01:43:42,990 --> 01:43:49,764 THAT. 2431 01:43:49,764 --> 01:43:52,733 THE TREND MORE RECENTLY -- I 2432 01:43:52,733 --> 01:43:53,601 SPOKE ABOUT THE MORE LOCAL 2433 01:43:53,601 --> 01:43:55,369 WORKING GROUP WE HAVE, HE BUT WE 2434 01:43:55,369 --> 01:43:58,239 FOMPLFORMED A NATIONAL WORKING P 2435 01:43:58,239 --> 01:44:00,641 AS WELL WHERE WE DISCUSS CASES 2436 01:44:00,641 --> 01:44:02,510 AND LOOK AT PATIENTS WITH AN EYE 2437 01:44:02,510 --> 01:44:03,411 TO DOING BOTH. 2438 01:44:03,411 --> 01:44:06,147 THE SAME CRITERIA WOULD BE 2439 01:44:06,147 --> 01:44:09,217 APPLIED WITH THE MELD CRITERIA. 2440 01:44:09,217 --> 01:44:11,085 >> SO HERE'S ANOTHER QUESTION. 2441 01:44:11,085 --> 01:44:14,021 IF THE CONVENTIONAL SO CALLED 2442 01:44:14,021 --> 01:44:19,193 LIVER FUNCTION TEST, WHICH YOU 2443 01:44:19,193 --> 01:44:19,827 ELEGANTLY CATEGORIZED AND SORT 2444 01:44:19,827 --> 01:44:23,030 OF PUT THEM IN THEIR PROPER 2445 01:44:23,030 --> 01:44:27,268 POSITION, IF THEY ARE INADEQUATE 2446 01:44:27,268 --> 01:44:31,772 FOR DIAGNOSING FONTAN RELATED 2447 01:44:31,772 --> 01:44:34,609 FIBROSIS, WHAT IN YOUR PROTOCOL 2448 01:44:34,609 --> 01:44:39,113 SEEKS TO FIND POTENTIAL OTHER 2449 01:44:39,113 --> 01:44:39,447 MARKERS? 2450 01:44:39,447 --> 01:44:47,989 I GUESS THIS GETS TO THE BASIC 2451 01:44:47,989 --> 01:44:51,058 NATURE OF HOW THE FIBROBLASTS 2452 01:44:51,058 --> 01:44:52,360 BECOME ACTIVATED, OR IS THAT 2453 01:44:52,360 --> 01:44:53,427 PART OF YOUR PROTOCOL? 2454 01:44:53,427 --> 01:44:53,928 >> YES. 2455 01:44:53,928 --> 01:44:55,563 WE'RE DOING A NUMBER OF -- WE'RE 2456 01:44:55,563 --> 01:44:57,498 LOOKING AT THE -- WE INTEND TO 2457 01:44:57,498 --> 01:44:59,867 LOOK AT THE TRANSCRIPTOME, WE 2458 01:44:59,867 --> 01:45:00,835 INTEND TO LOOK AT THE 2459 01:45:00,835 --> 01:45:01,402 TRANSCRIPTIONAL SIGNATURES 2460 01:45:01,402 --> 01:45:03,371 ACROSS THE LIVER. 2461 01:45:03,371 --> 01:45:04,572 WE INTEND TO LOOK AT A LOT OF 2462 01:45:04,572 --> 01:45:12,113 DIFFERENT MARKERS, BHOT BOTH IE 2463 01:45:12,113 --> 01:45:13,347 BLOOD AND THE LIVER AND WE'RE 2464 01:45:13,347 --> 01:45:14,649 ALSO COLLECTING THE STOOL 2465 01:45:14,649 --> 01:45:19,353 BECAUSE WE THINK THE CONGESTION. 2466 01:45:19,353 --> 01:45:20,888 GUT, PROTEIN ENTEROPATHY, 2467 01:45:20,888 --> 01:45:22,356 PERHAPS EXTREME DAMAGE TO THE 2468 01:45:22,356 --> 01:45:23,624 GUT, THAT THERE'S A SPECTRUM 2469 01:45:23,624 --> 01:45:23,991 BEFORE THAT. 2470 01:45:23,991 --> 01:45:26,627 SO WE WANT TO LOOK AND INTEGRATE 2471 01:45:26,627 --> 01:45:28,296 THAT AS WELL AND SEE IF WE CAN'T 2472 01:45:28,296 --> 01:45:30,364 FIND PREDICTORS OF DISEASE 2473 01:45:30,364 --> 01:45:30,665 PROGRESSION. 2474 01:45:30,665 --> 01:45:32,200 >> HERE'S ANOTHER QUESTION. 2475 01:45:32,200 --> 01:45:34,569 ISN'T THERE -- ARE THERE ANY 2476 01:45:34,569 --> 01:45:41,108 ANIMAL MODELS OF THE KIND OF 2477 01:45:41,108 --> 01:45:43,177 HEART DISEASE I GUESS MODELS 2478 01:45:43,177 --> 01:45:44,445 PRODUCE SURGICALLY RATHER THAN 2479 01:45:44,445 --> 01:45:45,513 CONGENITALLY OR MAYBE 2480 01:45:45,513 --> 01:45:45,846 CONGENITALLY. 2481 01:45:45,846 --> 01:45:50,318 ARE THERE ANY ANIMAL MODELS THAT 2482 01:45:50,318 --> 01:45:56,591 COULD PLAY A ROLE IN TRYING TO 2483 01:45:56,591 --> 01:45:57,592 ELUCIDATE ANSWERS TO SOME OF THE 2484 01:45:57,592 --> 01:46:02,630 QUESTIONS YOU ASK? 2485 01:46:02,630 --> 01:46:07,235 >> WELL, AS FAR AS AN MA MODELS 2486 01:46:07,235 --> 01:46:08,402 FOR HEART DISEASE, THERE ARE 2487 01:46:08,402 --> 01:46:08,869 VERY FEW. 2488 01:46:08,869 --> 01:46:12,940 AS YOU POINT OUT, IT WOULD BE -- 2489 01:46:12,940 --> 01:46:14,709 THAT ARE CREATED TAKING NORMAL 2490 01:46:14,709 --> 01:46:21,048 HEARTS AND TRYING TO REPLICATE 2491 01:46:21,048 --> 01:46:22,817 HEART DISEASE TO LOOK AT THINGS 2492 01:46:22,817 --> 01:46:26,220 SUCH AS -- I DON'T KNOW, MAYBE 2493 01:46:26,220 --> 01:46:35,096 THEO, YOU'RE AWARE ABOUT THAT. 2494 01:46:35,096 --> 01:46:39,133 >> SO HERE'S A PROVOCATIVE 2495 01:46:39,133 --> 01:46:43,838 QUESTION. 2496 01:46:43,838 --> 01:46:49,210 ARE THE RESPONSES OF THE CARDIAC 2497 01:46:49,210 --> 01:46:55,783 MYOCARDIUM A CONSEQUENCE OF 2498 01:46:55,783 --> 01:47:02,890 HYPOXIA OR IS THIS STRICTLY AN 2499 01:47:02,890 --> 01:47:06,961 EMBRYOLOGICALLY DRIVEN DEFECTS 2500 01:47:06,961 --> 01:47:08,396 EMBRYOLOGICALLY DRIVEN, IS THERE 2501 01:47:08,396 --> 01:47:14,402 A SECONDARY ROLE FOR HYPOXIA? 2502 01:47:14,402 --> 01:47:24,312 >> THE SHORT ANSWER IS YES. 2503 01:47:24,312 --> 01:47:25,846 WE STILL DON'T HAVE A 2504 01:47:25,846 --> 01:47:26,447 FUNDAMENTAL UNDERSTANDING OF 2505 01:47:26,447 --> 01:47:28,249 WHAT CAUSES MANY CONGENITAL 2506 01:47:28,249 --> 01:47:29,050 HEART DISEASES. 2507 01:47:29,050 --> 01:47:30,584 OBVIOUSLY IT ALL RELATES TO 2508 01:47:30,584 --> 01:47:31,018 GENES. 2509 01:47:31,018 --> 01:47:33,654 THERE HAVE BEEN VERY FEW IF ANY 2510 01:47:33,654 --> 01:47:35,323 SINGLE GENE MUTATIONS THAT HAVE 2511 01:47:35,323 --> 01:47:38,292 BEEN ASSOCIATED WITH THE TYPE OF 2512 01:47:38,292 --> 01:47:39,593 HEART DISEASE. 2513 01:47:39,593 --> 01:47:42,430 IT OFTEN -- THERE ARE 2514 01:47:42,430 --> 01:47:44,231 MULTIPLE -- ISSUES AND OTHER 2515 01:47:44,231 --> 01:47:47,601 THINGS, THERE'S SOME -- 2516 01:47:47,601 --> 01:47:50,338 TERATOGENS HAVE BEEN ASSOCIATED 2517 01:47:50,338 --> 01:47:54,608 WITH THAT AS WELL, AS WELL AS -- 2518 01:47:54,608 --> 01:48:00,114 THERE ARE CERTAIN TYPES OF DOWN 2519 01:48:00,114 --> 01:48:00,815 SYNDROME -- ASSOCIATED SPECIFIC 2520 01:48:00,815 --> 01:48:05,586 TYPE OF HEART DISEASE. 2521 01:48:05,586 --> 01:48:07,788 SO AS FAR AS THE FUNDAMENTAL 2522 01:48:07,788 --> 01:48:11,392 ETIOLOGY FOR HEART DISEASE, IT'S 2523 01:48:11,392 --> 01:48:13,828 OBVIOUSLY MANY, MULTIFACTORIAL 2524 01:48:13,828 --> 01:48:15,229 AND THEN WITH MANY ETIOLOGIES. 2525 01:48:15,229 --> 01:48:18,666 NOW AS FAR AS THE ISSUE OF 2526 01:48:18,666 --> 01:48:21,602 HYPOXIA, AND TISSUE HYPOXIA 2527 01:48:21,602 --> 01:48:22,269 SPECIFICALLY, THE SHORT ANSWER 2528 01:48:22,269 --> 01:48:26,006 IS YES, AND SO THAT IS WHY 2529 01:48:26,006 --> 01:48:28,642 PATIENTS WHO HAVE, SAY, CHRONIC 2530 01:48:28,642 --> 01:48:32,346 HYPOXIA, WE SEE EVIDENCE OF -- 2531 01:48:32,346 --> 01:48:37,985 TYPE INJURY, WE SEE THINGS SUCH 2532 01:48:37,985 --> 01:48:42,823 AS EFE -- OXIDATIVE STRESSES, 2533 01:48:42,823 --> 01:48:46,727 YET ONCE YOU HAVE A PATIENT WHO 2534 01:48:46,727 --> 01:48:48,195 HAS -- TISSUE AUTHORIZATION, 2535 01:48:48,195 --> 01:48:49,697 THEN WE DO SEE SOME CLINICAL 2536 01:48:49,697 --> 01:48:52,233 EFFECTS FROM THAT AS WELL. 2537 01:48:52,233 --> 01:48:56,103 IT'S NOTING NOT GOING TO HAVE 2538 01:48:56,103 --> 01:48:57,371 ALTERATIONS IN ANATOMY BUT IT'S 2539 01:48:57,371 --> 01:48:58,706 GOING TO HAVE DIRECT IMPACT ON 2540 01:48:58,706 --> 01:48:58,973 FUNCTION. 2541 01:48:58,973 --> 01:49:07,815 >> SO HERES A -- QUITE A PR 2542 01:49:07,815 --> 01:49:08,682 PROVOCATIVE QUESTION. 2543 01:49:08,682 --> 01:49:13,421 PRESUMABLY THE FIBROSIS PROCEEDS 2544 01:49:13,421 --> 01:49:19,560 FROM THE CENTRAL VENOUS AREA TO 2545 01:49:19,560 --> 01:49:21,629 THE PORTAL AREA. 2546 01:49:21,629 --> 01:49:23,130 SO THIS IS A THREE-PART 2547 01:49:23,130 --> 01:49:26,767 QUESTION. 2548 01:49:26,767 --> 01:49:29,103 DOES THIS CHANGE THE ZONAL 2549 01:49:29,103 --> 01:49:31,272 DISTRIBUTION OF HEPATIC 2550 01:49:31,272 --> 01:49:32,706 METABOLIC FUNCTION, WHICH IS 2551 01:49:32,706 --> 01:49:35,576 TURNING OUT TO BE, I THINK MORE 2552 01:49:35,576 --> 01:49:39,079 AND MORE OF M INTEREST AND 2553 01:49:39,079 --> 01:49:41,715 IMPORTANCE, ALL THESE LIVER 2554 01:49:41,715 --> 01:49:43,784 CELLS IN THE SINUSOID LOOK THE 2555 01:49:43,784 --> 01:49:45,252 SAME BUT THEY'RE DOING VERY 2556 01:49:45,252 --> 01:49:47,087 DIFFERENT THINGS UNDER DIFFERENT 2557 01:49:47,087 --> 01:49:48,722 STIMULI, HYPOXIA BEING ONE OF 2558 01:49:48,722 --> 01:49:50,925 THEM. 2559 01:49:50,925 --> 01:49:53,427 SO IS THERE A LINKAGE IN ANY WAY 2560 01:49:53,427 --> 01:49:55,396 OR RESEARCH TRYING TO DETERMINE 2561 01:49:55,396 --> 01:49:58,199 WHERE THE FIBROSIS OCCURS FIRST, 2562 01:49:58,199 --> 01:50:01,836 DOES IT HAVE EFFECTS ON THE 2563 01:50:01,836 --> 01:50:04,872 ZONAL DISTRIBUTION AND THEREBY 2564 01:50:04,872 --> 01:50:06,640 FUNCTION, AND THERE'S ALSO 2565 01:50:06,640 --> 01:50:13,013 SOMEONE IS ASKED WHILE YOU'RE AT 2566 01:50:13,013 --> 01:50:16,183 IT, IF THE EFFECT IS ESSENTIALLY 2567 01:50:16,183 --> 01:50:24,058 BLOCKADING THE LYMPHOID SYSTEM 2568 01:50:24,058 --> 01:50:25,893 AND PRODUCING ENTEROPATHY, IS 2569 01:50:25,893 --> 01:50:29,129 THAT A SENSITIVE INDEX FOR THE 2570 01:50:29,129 --> 01:50:30,164 DEVELOPMENT OF FIBROSIS OR IS 2571 01:50:30,164 --> 01:50:32,867 THAT REALLY JUST A LEITMAN 'FESS 2572 01:50:32,867 --> 01:50:33,100 TAITION? 2573 01:50:33,100 --> 01:50:39,707 DOLATEMANIFESTATION? 2574 01:50:39,707 --> 01:50:42,376 >> AS I MENTIONED THE FIBROSIS 2575 01:50:42,376 --> 01:50:44,245 IS DIFFERENT THAN VIRAL 2576 01:50:44,245 --> 01:50:45,412 HEPATITIS OR SOMETHING LIKE 2577 01:50:45,412 --> 01:50:50,451 THAT, IT DOES START SE CENTRALL, 2578 01:50:50,451 --> 01:50:50,818 THAT IS CORRECT. 2579 01:50:50,818 --> 01:50:53,554 I DON'T KNOW ANYBODY WHO'S 2580 01:50:53,554 --> 01:50:58,459 STUDIED DIFFERENCES IN FUNCTION, 2581 01:50:58,459 --> 01:51:03,631 IN CIRRHOSIS ITSELF, WE USE A -- 2582 01:51:03,631 --> 01:51:07,268 TO LOOK AT DISTRIBUTION AND SO 2583 01:51:07,268 --> 01:51:10,571 THERE MAY BE SOME SIMPLE WAYS TO 2584 01:51:10,571 --> 01:51:14,174 LOOK AT A SIMPLISTIC APPROACH 2585 01:51:14,174 --> 01:51:17,578 TO -- IN THE FONTAN LIVER, BUT I 2586 01:51:17,578 --> 01:51:19,246 THINK -- IF WE THINK ABOUT THE 2587 01:51:19,246 --> 01:51:20,114 NORMAL OXYGEN TENSION IN THE 2588 01:51:20,114 --> 01:51:23,717 LIVER, IT'S 12%, 8% AND 3%, ZONE 2589 01:51:23,717 --> 01:51:24,718 THREE, HERE IT MUST BE EVEN 2590 01:51:24,718 --> 01:51:25,386 LOWER THAN THAT. 2591 01:51:25,386 --> 01:51:28,689 MUCH LOWER THAN THAT. 2592 01:51:28,689 --> 01:51:33,060 SO I WONDER HOW SEW ZONATION 2593 01:51:33,060 --> 01:51:35,396 WOULD WORK EVEN IN THE NON- -- I 2594 01:51:35,396 --> 01:51:36,897 THINK IT'S AN INCREDIBLY 2595 01:51:36,897 --> 01:51:41,502 INTERESTING QUESTION. 2596 01:51:41,502 --> 01:51:43,504 WE MAY BE ABLE TO LOOK AT IT IN 2597 01:51:43,504 --> 01:51:52,146 SOME WAYS. 2598 01:51:52,146 --> 01:51:53,647 LOOKING AT TRANSCRIPTION IN SITU 2599 01:51:53,647 --> 01:51:54,982 AND I THINK WE MAY GET SOME 2600 01:51:54,982 --> 01:51:56,917 ANSWERS FOR THAT. 2601 01:51:56,917 --> 01:51:58,218 WE'RE OBVIOUSLY INTERESTED IN 2602 01:51:58,218 --> 01:51:58,986 CONTINUED METABOLIC FUNCTION AND 2603 01:51:58,986 --> 01:52:00,087 HOW THAT'S AFFECT BID ALL THESE 2604 01:52:00,087 --> 01:52:03,958 DIFFERENT THINGS. 2605 01:52:03,958 --> 01:52:05,459 PROTEIN -- ENTEROPATHY IS I 2606 01:52:05,459 --> 01:52:07,661 THINK AN EXTREME, IT'S NOT JUST 2607 01:52:07,661 --> 01:52:10,164 AS SIMPLE AS LYMPHATICS, I THINK 2608 01:52:10,164 --> 01:52:11,966 IT'S ALSO CONGESTION IN THE GUT 2609 01:52:11,966 --> 01:52:17,972 AND BACK PRESSURE IN THE GUT. 2610 01:52:17,972 --> 01:52:19,640 IT'S NOT A SENSITIVE ENOUGH 2611 01:52:19,640 --> 01:52:20,741 MARKER TO IDENTIFY PATIENTS WITH 2612 01:52:20,741 --> 01:52:27,214 LIVER DISEASE, FOR SURE NOT. 2613 01:52:27,214 --> 01:52:29,149 >> HERE'S ANOTHER ONE. 2614 01:52:29,149 --> 01:52:32,052 DO WE KNOW ANYTHING ABOUT THE 2615 01:52:32,052 --> 01:52:36,523 SIZE OF THE HEPATIC SIGH EU SOY 2616 01:52:36,523 --> 01:52:47,201 DALSINUSOIDALFENESTRA, DOES IT S 2617 01:52:47,201 --> 01:52:47,468 FUNCTION? 2618 01:52:47,468 --> 01:52:53,674 >> WE DON'T KNOW, BUT WHEN WE DO 2619 01:52:53,674 --> 01:52:54,975 THE ELECTRON MICROSCOPY, WE 2620 01:52:54,975 --> 01:52:56,076 SHOULD HAVE A BETTER ANSWER TO 2621 01:52:56,076 --> 01:52:57,845 WHAT THEY ACTUALLY LOOK LIKE AND 2622 01:52:57,845 --> 01:53:00,147 IF THEY'VE CHANGED AT ALL IN 2623 01:53:00,147 --> 01:53:06,186 THIS SETTING. 2624 01:53:06,186 --> 01:53:09,923 >> TOM, WE HAVE THE INEVITABLE 2625 01:53:09,923 --> 01:53:13,193 PRACTICAL QUESTION THAT WHEN 2626 01:53:13,193 --> 01:53:15,262 SOME GREAT ADVANCE HAS TAKEN 2627 01:53:15,262 --> 01:53:17,231 PLACE, THAT BECOMES HIGHLY 2628 01:53:17,231 --> 01:53:20,100 SPECIALIZED, AND THE QUESTION 2629 01:53:20,100 --> 01:53:23,570 ALWAYS IS, WHO PAYS FOR IT, AND 2630 01:53:23,570 --> 01:53:29,109 IS THIS COVERED IN ANY FORM OF 2631 01:53:29,109 --> 01:53:29,977 AVAILABLE HEALTH INSURANCE, YOU 2632 01:53:29,977 --> 01:53:33,514 KNOW, TO THE LARGE MASS OF 2633 01:53:33,514 --> 01:53:34,715 PEOPLE, PARTICULARLY GIVEN THAT 2634 01:53:34,715 --> 01:53:39,119 SITS A RARE DISORDER? 2635 01:53:39,119 --> 01:53:45,492 >> SO THE QUESTION, IS IT NEW 2636 01:53:45,492 --> 01:53:46,794 INTERVENTIONS OR QUESTIONS ABOUT 2637 01:53:46,794 --> 01:53:48,595 SURGERY FOR HYPOPLASTIC -- 2638 01:53:48,595 --> 01:53:49,697 >> THE WHOLE THING. 2639 01:53:49,697 --> 01:53:50,531 >> OKAY. 2640 01:53:50,531 --> 01:53:51,865 WELL, FOR THE MOST PART, THESE 2641 01:53:51,865 --> 01:53:54,501 HAVE BECOME STANDARD OF CARE, SO 2642 01:53:54,501 --> 01:54:00,774 GIVE A PATIENT A HYPOPLASTIC 2643 01:54:00,774 --> 01:54:03,744 LEFT HEART, ATRESIA,S IS 2644 01:54:03,744 --> 01:54:06,146 STANDARD CARE, SO PAYOR WILL 2645 01:54:06,146 --> 01:54:11,985 COVER FOR THE SURGERY. 2646 01:54:11,985 --> 01:54:17,891 IT DEPENDS ON YOUR OUT OF POCKET 2647 01:54:17,891 --> 01:54:22,162 EXPENSES, BUT IT'S NOT UNCOMMON 2648 01:54:22,162 --> 01:54:24,565 FOR FOLKS TO BE ON THE PHONE 2649 01:54:24,565 --> 01:54:25,365 ARGUING WITH THE INSURANCE 2650 01:54:25,365 --> 01:54:26,900 COMPANY, BUT IN GENERAL, IT IS A 2651 01:54:26,900 --> 01:54:27,768 COVERED BENEFIT. 2652 01:54:27,768 --> 01:54:37,044 SOMETIMES THE AREA BECOMES IF 2653 01:54:37,044 --> 01:54:38,746 THERE ARE NEW TECHNOLOGIES THAT 2654 01:54:38,746 --> 01:54:39,613 HAVE COME ON THE MARKET. 2655 01:54:39,613 --> 01:54:43,884 FOR EXAMPLE, I MENTIONED THE 2656 01:54:43,884 --> 01:54:45,452 CLOSURE DEVICE, WE KIND OF 2657 01:54:45,452 --> 01:54:48,188 BREEZED THROUGH THAT. 2658 01:54:48,188 --> 01:54:52,359 BUT THAT'S -- LIVER TO THE 2659 01:54:52,359 --> 01:54:54,595 CATHETER TO CLOSE UP A HOLE IN 2660 01:54:54,595 --> 01:54:55,395 THE HEART. 2661 01:54:55,395 --> 01:54:57,865 NOW THOSE THINGS, DEPENDING UPON 2662 01:54:57,865 --> 01:54:58,899 THE INSURANCE COMPANY, THEY MAY 2663 01:54:58,899 --> 01:55:02,903 OR MAY NOT BE WILLING TO COVER 2664 01:55:02,903 --> 01:55:05,773 THINGS THAT ARE IN PHASE THREE 2665 01:55:05,773 --> 01:55:08,609 TRIAL, POLICY BY POLICY, BUT 2666 01:55:08,609 --> 01:55:09,943 MEDICARE -- MEDICAID WILL COVER 2667 01:55:09,943 --> 01:55:12,346 FOR SURGERY, BUT -- AND IT'S A 2668 01:55:12,346 --> 01:55:13,614 GOOD QUESTION. 2669 01:55:13,614 --> 01:55:16,784 AND IT CAN BE VERY EXPENSIVE. 2670 01:55:16,784 --> 01:55:18,519 ONE OF THE COMPLICATIONS IS NOT 2671 01:55:18,519 --> 01:55:19,787 SIMPLY THE SURGERY ITSELF BUT 2672 01:55:19,787 --> 01:55:26,527 THE FOLLOW-ON CARE AS WELL. 2673 01:55:26,527 --> 01:55:29,229 NOW YOU ARE COVERED BY MILITARY 2674 01:55:29,229 --> 01:55:30,864 HEALTH, I DON'T KNOW IF YOU HAVE 2675 01:55:30,864 --> 01:55:31,865 ANY EXPERIENCE THAT YOU WANT TO 2676 01:55:31,865 --> 01:55:34,701 TALK ABOUT. 2677 01:55:34,701 --> 01:55:37,971 >> THE INSURANCE COMPANY -- 2678 01:55:37,971 --> 01:55:39,740 WELL, SHE'S NOT IN THE MILITARY 2679 01:55:39,740 --> 01:55:46,113 ANYMORE BALLS SHE'S SHE'S OVER T 2680 01:55:46,113 --> 01:55:47,548 DOESN'T COVER AFTER THE AGE OF 2681 01:55:47,548 --> 01:55:48,081 23. 2682 01:55:48,081 --> 01:55:52,286 SHE FORTUNATELY -- SHE HAS -- 2683 01:55:52,286 --> 01:55:54,588 THROUGH HER WORK, SHE HAS 2684 01:55:54,588 --> 01:55:55,355 INSURANCE, WHICH HAS BEEN 2685 01:55:55,355 --> 01:55:57,591 GRADE -- I MEAN, BEING IN THE 2686 01:55:57,591 --> 01:55:59,993 MILITARY OBVIOUSLY WE DON'T PAY 2687 01:55:59,993 --> 01:56:00,894 FOR NOTHING. 2688 01:56:00,894 --> 01:56:02,129 IT'S LIKE EVERYTHING IS DONE FOR 2689 01:56:02,129 --> 01:56:03,864 YOU, MEDICINE-WISE. 2690 01:56:03,864 --> 01:56:05,966 WITH HER INSURANCE, LUCKILY THEY 2691 01:56:05,966 --> 01:56:07,034 COVER 80% WHICH IS BETTER THAN 2692 01:56:07,034 --> 01:56:09,269 NOT HAVING INSURANCE, SO IN THAT 2693 01:56:09,269 --> 01:56:11,238 REGARDS, WE'RE BLESSED IN THAT 2694 01:56:11,238 --> 01:56:12,773 REGARD, YOU KNOW? 2695 01:56:12,773 --> 01:56:16,476 WE HAVEN'T COME ACROSS ANYTHING 2696 01:56:16,476 --> 01:56:17,978 THAT'S BEEN A PROBLEM OF GETTING 2697 01:56:17,978 --> 01:56:21,582 HELP OR CARE BASED ON -- THERE'S 2698 01:56:21,582 --> 01:56:22,783 A LITTLE MORE RED TAPE YOU HAVE 2699 01:56:22,783 --> 01:56:24,251 TO GO THROUGH, A LOT OF 2700 01:56:24,251 --> 01:56:25,018 REFERRALS TO GET TO WHERE YOU 2701 01:56:25,018 --> 01:56:27,654 NEED TO BE, BUT OVERALL, WE'VE 2702 01:56:27,654 --> 01:56:37,965 BEEN LUCKY, YEAH. 2703 01:56:39,366 --> 01:56:44,438 >> EXCUSE ME. 2704 01:56:44,438 --> 01:56:46,673 SORRY. 2705 01:56:46,673 --> 01:56:47,474 HERE YOU ARE. 2706 01:56:47,474 --> 01:56:50,477 THEO. 2707 01:56:50,477 --> 01:56:53,213 DO WE KNOW ABOUT THE 2708 01:56:53,213 --> 01:56:55,148 DISTRIBUTION OF STELLATE CELLS 2709 01:56:55,148 --> 01:56:59,019 IN THE FONTAN LIVER? 2710 01:56:59,019 --> 01:57:01,188 THIS PERSON SAYS THAT NORMALLY 2711 01:57:01,188 --> 01:57:03,991 THEY ARE MORE PROMINENT IN THE 2712 01:57:03,991 --> 01:57:08,128 PROXIMAL RATHER THAN THE DISTAL 2713 01:57:08,128 --> 01:57:09,563 SINUSOID, I DIDN'T REALIZE THAT, 2714 01:57:09,563 --> 01:57:10,864 BUT IS THERE A BIG SHIFT? 2715 01:57:10,864 --> 01:57:12,132 DO WE KNOW WHAT THE TYPE OF 2716 01:57:12,132 --> 01:57:15,068 COLLAGEN IS, PRESUMABLY IF IT'S 2717 01:57:15,068 --> 01:57:16,470 REVERSIBLE. 2718 01:57:16,470 --> 01:57:18,705 IT'S TYPE I COLLEGE AND IT'S NOT 2719 01:57:18,705 --> 01:57:20,040 CROSS LINKED. 2720 01:57:20,040 --> 01:57:23,410 SO WITH TIME, DOES IT BECOME 2721 01:57:23,410 --> 01:57:26,046 CROSS LINKED, IN WHICH CASE IT 2722 01:57:26,046 --> 01:57:30,684 PROBABLY WOULD NOT RESOLVE. 2723 01:57:30,684 --> 01:57:31,685 AFTER HEART SURGERY, FOR 2724 01:57:31,685 --> 01:57:33,587 EXAMPLE. 2725 01:57:33,587 --> 01:57:35,822 >> A LOT OF THE THINGS WE TAKE 2726 01:57:35,822 --> 01:57:38,325 FOR GRANTED IN LIVER DISEASE IS 2727 01:57:38,325 --> 01:57:39,493 NOT KNOWN IN FONTAN. 2728 01:57:39,493 --> 01:57:42,896 NO ONE KNOWS -- I DON'T THINK 2729 01:57:42,896 --> 01:57:44,498 THERE'S A SINGLE PUBLICATION 2730 01:57:44,498 --> 01:57:46,867 LOOKING AT STELLATE CELLS IN THE 2731 01:57:46,867 --> 01:57:49,169 FONTAN LIVER. 2732 01:57:49,169 --> 01:57:51,238 THERE IS NOT A SINGLE -- WHICH 2733 01:57:51,238 --> 01:57:52,673 REALLY LOOKS AT THE COLLAGEN, 2734 01:57:52,673 --> 01:57:55,175 TYPE OF COLLAGEN, COLLAGEN 2735 01:57:55,175 --> 01:57:56,443 DISTRIBUTION EXCEPT FOR THE 2736 01:57:56,443 --> 01:57:59,079 PATTERN OF CIRRHOSIS IN FONTAN. 2737 01:57:59,079 --> 01:58:03,483 SO THIS IS A FIELD THAT 2738 01:58:03,483 --> 01:58:04,584 DESPERATELY NEEDS STUDY AND THE 2739 01:58:04,584 --> 01:58:05,786 THINGS WE TAKE FOR GRANTED IN 2740 01:58:05,786 --> 01:58:07,154 MOST LIVER DISEASES HAVE NOT 2741 01:58:07,154 --> 01:58:12,292 BEEN EXPLORED AT ALL. 2742 01:58:12,292 --> 01:58:16,563 >> WELL, YOU'VE POINTED OUT THE 2743 01:58:16,563 --> 01:58:19,599 GREAT EXCITING CHALLENGE, AND I 2744 01:58:19,599 --> 01:58:23,370 THINK AGAIN, FOR THE PURPOSE OF 2745 01:58:23,370 --> 01:58:28,308 THE DEMYSTIFYING MEDICINE 2746 01:58:28,308 --> 01:58:34,514 HYPOTHESIS, THIS IS A BEAUTIFUL 2747 01:58:34,514 --> 01:58:36,216 EXAMPLE OF THE NEED FOR 2748 01:58:36,216 --> 01:58:38,185 EXTENSIVE BRIDGING AND 2749 01:58:38,185 --> 01:58:41,221 COMMUNICATION AMONGST PEOPLE WHO 2750 01:58:41,221 --> 01:58:43,991 VERY OFTEN LIVE IN SILOS. 2751 01:58:43,991 --> 01:58:46,093 WE HAVE ONE LAST QUESTION FOR 2752 01:58:46,093 --> 01:58:49,196 YOU, TOM, OR MAYBE THEO, AND 2753 01:58:49,196 --> 01:58:55,102 THAT IS, HOW DOES THE SINUSOID 2754 01:58:55,102 --> 01:58:57,204 HANDLE ARTERIAL BLOOD AT 2755 01:58:57,204 --> 01:59:00,474 120 MILLIMETERS OF MERCURY 2756 01:59:00,474 --> 01:59:02,376 INJECTED INTO THE SINUSOID, 2757 01:59:02,376 --> 01:59:04,444 WHERE MOST OF THE BLOOD FROM THE 2758 01:59:04,444 --> 01:59:08,382 PORTAL SYSTEM IS AT MUCH, MUCH 2759 01:59:08,382 --> 01:59:10,784 LOWER PRESSURE. 2760 01:59:10,784 --> 01:59:13,353 HOW DOES THE LIVER PREVENT THE 2761 01:59:13,353 --> 01:59:17,624 SINUSOID FROM EXPLODING? 2762 01:59:17,624 --> 01:59:21,561 >> WELL, BY THE TIME IT REACHES 2763 01:59:21,561 --> 01:59:24,564 THE CAPILLARY BED, IT'S GOING TO 2764 01:59:24,564 --> 01:59:27,801 BE A -- THE PRESSURES AT THAT 2765 01:59:27,801 --> 01:59:32,973 POINT WILL REACH MUCH LOWER 2766 01:59:32,973 --> 01:59:33,306 LEVELS. 2767 01:59:33,306 --> 01:59:35,976 I'M GUESSING IN THE PORTAL 2768 01:59:35,976 --> 01:59:37,177 SYSTEM 15 MILLIMETERS OF 2769 01:59:37,177 --> 01:59:38,378 MERCURY? 2770 01:59:38,378 --> 01:59:42,115 SO IF THAT ATTENUATION OF 2771 01:59:42,115 --> 01:59:43,517 PRESSURE AS IT GETS DOWNSTREAM. 2772 01:59:43,517 --> 01:59:46,420 >> SO THE TEXTBOOK DIAGRAMS, THE 2773 01:59:46,420 --> 01:59:49,456 CARTOONS ARE WRONG BECAUSE THEY 2774 01:59:49,456 --> 01:59:51,892 IMPLY A BRANCH OF THE HEPATIC 2775 01:59:51,892 --> 01:59:54,294 ARTERY, AND IN TRUTH, IT IS A 2776 01:59:54,294 --> 01:59:56,363 BRANCH, BUT IT'S THE CAPILLARY 2777 01:59:56,363 --> 01:59:56,596 BRANCH. 2778 01:59:56,596 --> 02:00:03,437 IS THAT THE POINT? 2779 02:00:03,437 --> 02:00:03,870 >> YES. 2780 02:00:03,870 --> 02:00:05,038 >> OKAY. 2781 02:00:05,038 --> 02:00:11,711 WELL, LISTEN, WE WANT TO THANK 2782 02:00:11,711 --> 02:00:13,280 BOTH OF YOU FOR -- YES, THEO. 2783 02:00:13,280 --> 02:00:14,514 >> CAN I SAY ONE THING? 2784 02:00:14,514 --> 02:00:16,550 THIS CAN ONLY BE DONE AT A PLACE 2785 02:00:16,550 --> 02:00:17,717 LIKE THE CLINICAL CENTER. 2786 02:00:17,717 --> 02:00:21,755 WHERE ELSE COULD I GO, COULD WE 2787 02:00:21,755 --> 02:00:22,923 ACCUMULATE THIS MANY PATIENTS, 2788 02:00:22,923 --> 02:00:26,493 FIND A WILLING PARTNER LIKE 2789 02:00:26,493 --> 02:00:27,494 DR. BURKLOW, AND TO LOOK AT A 2790 02:00:27,494 --> 02:00:28,795 DISEASE IN HUMANS, NOT IN 2791 02:00:28,795 --> 02:00:32,732 ANIMALS BUT IN HUMANS, AND I 2792 02:00:32,732 --> 02:00:36,069 THINK THIS ALSO SPEAKS TO NOT 2793 02:00:36,069 --> 02:00:41,975 ONLY THE HIGH BOTH HYPOTHESIS F 2794 02:00:41,975 --> 02:00:43,877 DEMYSTIFYING MEDICINE BUT ALSO 2795 02:00:43,877 --> 02:00:45,846 THE CLINICAL COMMUNITY, AND IT'S 2796 02:00:45,846 --> 02:00:46,813 IMPORTANT FOR ME TO SAY THANK 2797 02:00:46,813 --> 02:00:47,914 YOU FOR THE PEOPLE LIKE THAT 2798 02:00:47,914 --> 02:00:49,950 THAT HAVE REALLY MADE THIS 2799 02:00:49,950 --> 02:00:50,217 POSSIBLE. 2800 02:00:50,217 --> 02:00:56,723 >> TO GO BACK TO ANGELICA, WHAT 2801 02:00:56,723 --> 02:00:57,824 SHE SAID AT THE BEGINNING, IT 2802 02:00:57,824 --> 02:01:01,161 DOES TAKE A VILLAGE, NOT JUST 2803 02:01:01,161 --> 02:01:03,763 FRONT LINE PROVIDERS LIKE YOU 2804 02:01:03,763 --> 02:01:05,198 TRYING TO SOLVE A PLEX PROBLEM, 2805 02:01:05,198 --> 02:01:07,868 SO IT'S MY HONOR TO SUPPORT YOU 2806 02:01:07,868 --> 02:01:10,504 IN YOUR WORK AND TO BE HERE AT 2807 02:01:10,504 --> 02:01:12,038 THE CLINICAL CENTER. 2808 02:01:12,038 --> 02:01:13,073 >> ALL RIGHT. 2809 02:01:13,073 --> 02:01:20,080 LISTEN, I WANT TO THANK THE 2810 02:01:20,080 --> 02:01:22,015 PATIENT AND HER MOTHER AND BOTH 2811 02:01:22,015 --> 02:01:26,286 OF YOU FOR BRINGING THIS ISSUE 2812 02:01:26,286 --> 02:01:30,457 TO LIGHT TO A LARGE NUMBER OF 2813 02:01:30,457 --> 02:01:31,591 PEOPLE WHO KNEW LITTLE OR 2814 02:01:31,591 --> 02:01:33,226 NOTHING ABOUT IT AND I'M SURE 2815 02:01:33,226 --> 02:01:37,330 WILL BE HIGHLY MOTIVATED TO 2816 02:01:37,330 --> 02:01:40,267 THINK OF THEIR EXPERTISE AND HOW 2817 02:01:40,267 --> 02:01:44,871 IT MAY CONTRIBUTE TO 2818 02:01:44,871 --> 02:01:45,739 UNDERSTANDING SOME OF THE 2819 02:01:45,739 --> 02:01:50,010 IMPORTANT ISSUES RAISED FROM THE 2820 02:01:50,010 --> 02:01:52,913 STANDPOINT OF BASIC SCIENCE AND 2821 02:01:52,913 --> 02:01:55,448 OF COURSE IN RELATIONSHIP TO 2822 02:01:55,448 --> 02:01:58,952 IMPROVE MANAGEMENT OF THIS 2823 02:01:58,952 --> 02:01:59,486 DISORDER. 2824 02:01:59,486 --> 02:02:04,124 SO THANK YOU ALL FOR A VERY 2825 02:02:04,124 --> 02:02:06,860 EXCITING PRESENTATION, WHICH I'M 2826 02:02:06,860 --> 02:02:08,395 SURE I SPEAK ON BEHALF OF MANY 2827 02:02:08,395 --> 02:02:11,665 HUNDREDS OF PEOPLE WHO 2828 02:02:11,665 --> 02:02:14,568 APPRECIATE THIS VERY MUCH. 2829 02:02:14,568 --> 02:02:19,940 SO THANK YOU. 2830 02:02:19,940 --> 02:02:30,183 >> THANK YOU.