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WELCOME TO THE CLINICAL
CENTER GRAND ROUNDS,

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A WEEKLY SERIES OF EDUCATIONAL
LECTURES FOR PHYSICIANS AND

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HEALTH CARE PROFESSIONALS
BROADCAST FROM THE CLINICAL

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CENTER AT THE NATIONAL
INSTITUTES OF HEALTH IN

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BETHESDA, MD.

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THE NIH CLINICAL CENTER IS THE
WORLD'S LARGEST HOSPITAL TOTALLY

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DEDICATED TO INVESTIGATIONAL
RESEARCH AND LEADS THE GLOBAL

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EFFORT IN TRAINING TODAY'S
INVESTIGATORS AND DISCOVERING

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TOMORROW'S CURES.

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LEARN MORE BY VISITING US ONLINE
AT HTTP://CLINICALCENTER.NIH.GOV

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GOOD AFTERNOON.

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THANK YOU ALL.

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WELCOME TO TODAY'S CLINICAL

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CENTER GRAND ROUNDS.

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THE HOPKINS CLOUD CME ACTIVITY

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CODE FOR TODAY'S GRAND ROUNDS IS

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LISTED ON THE BOARD THERE.

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57905.

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PLEASE TEXT THIS CODE TO THE

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JOHNS HOPKINS CME PHONE NUMBER

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ON THE SLIDE TO RECEIVE YOUR CME

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CREDIT.

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WE KINDLY INVITE YOU TO PROVIDE

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FEEDBACK FOR TODAY'S LECTURE BY

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SCANNING THE QR CODE SHOWN ON

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THE CME SLIDE.

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FOR THOSE APPLYING FOR CME, YOU

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WILL RECEIVE A FEEDBACK LINK VIA

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EMAIL.

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THIS WILL BE USED TO PROVIDE US

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WITH IMPORTANT FEEDBACK ABOUT

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THIS PRESENTATION AND ALLOWS US

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TO SUBMIT ANY SUGGESTIONS FOR

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FUTURE GRAND ROUND TOPICS.

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DURING THE PRESENTATION,

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QUESTIONS FOR THE SPEAKERS WILL

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BE TAKEN FROM THE MICROPHONE IN

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THE AISLE.

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ADDITIONALLY, VIDEOCAST VIEWERS

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MAY SUBMIT QUESTIONS AT ANY TIME

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DURING THE LECTURE BY SCROLLING

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DOWN AND CLICKING THE LIVE

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FEEDBACK BUTTON LOCATED AT THE

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VIDEOCAST WEBSITE.

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QUESTIONS WILL BE ANSWERED AS

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TIME PERMITS AT THE CONCLUSION

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OF THE PRESENTATION.

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OUR SPEAKERS TODAY, THREE

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PEOPLE.

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DR. SEAN AGBOR, THAT'S ME,

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DR. ASHLEY PARK, AND DR. CONNOR

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O'BRIEN.

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I WILL START WITH AN

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INTRODUCTION OF DR. CONNOR

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O'BRIEN, JUST WITH KIND

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PERMISSION, ONE MINUTE, PLEASE.

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DR. CONNOR O'BRIEN IS A

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COLLABORATOR OF OURS, WE'VE

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COLLABORATED FOR A FEW YEARS

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NOW.

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BRILLIANT SCIENTIST.

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HE'S A CRITICAL CARE TRAINED

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CARDIOLOGIST, TRAINED CURRENTLY

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AT THE UNIVERSITY OF CALIFORNIA

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SAN FRANCISCO, WHERE HE HOLDS

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THE POSITION OF ASSOCIATE

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DIRECTOR OF THE CARDIAC ICU.

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DR. O'BRIEN COMPLETED MEDICAL

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SCHOOL IN COLOMBIA, FELLOWSHIP

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STANFORD, AND NOW TOOK UP A JOB

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AS ASSOCIATE DIRECTOR OF THE

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CICU AT THE UNIVERSITY OF

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SAN FRANCISCO, WHERE HE

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CO-DIRECTS THE UNIT WITH CHRIS

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BARNETT, WHO DID HIS TRAINING

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HERE WITH US AS WELL.

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RESEARCH-WISE, DR. O'BRIEN IS

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ONE OF REALLY OUR NATION'S

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LEADER IN CARDIOGENIC SHOCK.

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HE WORKS ON BIOMARKERS IN

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DESCRIBING PHYSIOLOGICAL CHANGES

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THAT ARE CAUSED IN THESE

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UNFORTUNATE PATIENTS WHO DEVELOP

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CARDIOGENIC SHOCK.

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OUTSIDE OF WORK, HE'S A

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WONDERFUL HUSBAND, WONDERFUL

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FRIEND, FATHER OF TWO GIRLS, AND

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HE PLAYS RUGBY.

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YOU DON'T WANT TO MEET HIM

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THERE, I TELL YOU THAT.

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SO HOPEFULLY WE'LL HEAR HIS TALK

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AFTER THIS.

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AFTER DR. O'BRIEN, I HAVE ALSO

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THE REAL DISTINCT PRIVILEGE OF

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INTRODUCING DR. ASHLEY PARK.

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A FELLOW HERE WITH US IN THE

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CRITICAL MEDICINE DEPARTMENT

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HERE AT NHLBI.

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I'VE KNOWN DR. PARK FOR ABOUT

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TWO YEARS NOW, SHE DOES HER

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RESEARCH IN THE LAB.

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UNDERGRADUATE DEGREE AT

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DARTMOUTH MEDICAL SCHOOL

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PITTSBURGH, MED PEDS RESIDENCY

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THE A GEORGETOWN, SHE ALSO

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SERVED AS CHIEF RESIDENT AND

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THEN JOINED OUR CRITICAL CARE

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MEDICINE DEPARTMENT HERE AS A

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FELLOW AND CURRENTLY DOES

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RESEARCH IN THE LAB.

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I WILL LET DR. PARK'S WORK IN

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THE LAB SPEAK FOR ITSELF, AND

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MAYBE IT THEN WILL BECOME QUITE

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CLEAR WHY SHE'S SUCH A

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REMARKABLE FELLOW, AND I'VE

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JUST -- HAD MAJOR FELLOWSHIP

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APPOINTMENTS AND MAJOR

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UNIVERSITIES ACROSS THE NATION.

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I'VE BEEN EXTREMELY FORTUNATE TO

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BE HER MENTOR, RESEARCH MENTOR

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DURING THIS TIME.

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WITHOUT MUCH ADO, I WILL STOP

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HERE AND I WILL PASS IT OVER TO

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DR. O'BRIEN TO START -- TO GIVE

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THE FIRST SET OF THE LECTURES.

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THANK YOU.

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[APPLAUSE]

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>> IT'S A PLEASURE TO BE
HERE.

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THANK YOU VERY, VERY MUCH FOR

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HAVING ME AND COLLABORATING WITH

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THESE TWO HAS BEEN ABSOLUTELY A

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PLEASURE.

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LOOKING FORWARD TO MANY MORE

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YEARS TO COME.

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SO WITHOUT FURTHER ADO, WE'RE

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GOING TO TALK ABOUT CARDIOGENIC

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SHOCK AND WE'VE ENTITLED THIS

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FIRE BEFORE THERE IS SMOKE, AND

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IDEA BEING IT'S OUR CURRENT WAY

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OF IDENTIFYING CARDIOGENIC SHOCK

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IS TOO LATE.

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AND WE'LL GO THROUGH THAT HERE

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IN THE NEXT FEW SLIDES.

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I HAVE A SINGLE DISCLOSURE,

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WORKING FOR JOHNSON, JOHNSON MED

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TECH AS A CONSULTANT.

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SO WE'RE GOING TO START TALKING

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ABOUT A CONTEMPORARY VIEW OF

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CARD CARDIOGENIC SHOCK, WHAT ISH

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RISK PHYSIOLOGY, AND THEN LOOK

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AT THE LOGISTICAL CHALLENGES FOR

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DELIVERING CARE THAT REALLY SET

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THESE PATIENTS BACK, AND THEN

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NOVEL TECHNIQUES FOR IDENTIFYING

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THEM EARLIER TO GIVE US BETTER

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OPPORTUNITIES TO RESPOND TO THIS

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REALLY HIGH RISK DISEASE STATE.

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SO BEFORE WE GO FORWARD TO

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MODERN SCIENCE, IT'S HELP TOWEL

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TO KNOW WHERE WE CAME FROM AND

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UNDERSTAND THE PITFALLS THAT

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HELD THE STUDY BACK OF

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CARDIOGENIC SHOCK.

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IN CARDIOLOGY WE HAVE TONS OF

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DATA WHICH GIVES US LOTS OF

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HISTORICAL CONTEXT AND WE CAN GO

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ALL THE WAY BACK TO DESMOND

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JULIAN IN THE 1960s WHEN THE

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FIRST CCU WAS DEVELOPED.

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THIS WAS DEVELOPED BY COHORTING

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PATIENTS WHO ARE SUSPECTED TO

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HAVE AN M.I. TOGETHER TO LOOK

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FOR EARLY SIGNS OF V TV F AND

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OFFERING EARLY DEFIBRILLATION.

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THIS WAS OFFERED BY THOMAS

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KILLUP, HIS CONTRIBUTION WAS TO

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GET TRAINED NURSES TO

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DEFIBRILLATE.

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SO HE EXPANDED THE CARE TEAM,

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THE IDEA THAT SORT OF TAKING

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DOWR BARRIERS, IT DOESN'T NEED

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TO BE A PHYSICIAN TO PUSH THIS

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BUTTON.

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WE NEED EARLY RECOGNITION.

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IT'S BETDER BETTER TO DO THINGS,

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LET'S MAKE THIS TEAM BIGGER AND

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MORE COLLABORATIVE.

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WE THEN MOVE FORWARD IN THE

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PIPELINE WHERE WE START SEEING

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COAGULATIONS COME OUT, LYTICS,

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STENTS, AND THEN STENTS COME

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WITH SOME STRUCTURAL CHANGES IN

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RESPONSE NETWORKS AND EMS

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NETWORKS THAT WERE DEVELOPED AND

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WE GET TO THE MORTALITY IN ACS

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WE ENJOY TODAY WHICH IS ABOUT

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2 TO 4%.

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OVERLYING THAT MORTALITY IS THE

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MORTALITY OF CARDIOGENIC SHOCK.

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AND AGAIN, THIS IS ALL FOR AMI,

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SO WE'LL TALK A LITTLE MORE

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ABOUT OTHER STATE IN A LITTLE

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BIT.

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BUT YOU CAN SEE THE MORTALITY IS

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MUCH, MUCH HIGHER.

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AND WHEN THERAPIES COME OUT

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LIKELY TICKS, PCI, THERE IS SOME

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MODEST IMPROVEMENT IN MORTALITY,

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BUT AGAIN, VERY, VERY MODEST.

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FOLLOWING THE LATE '90S, YOU SEE

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A QUICK DROP AFTER THE SHOCK

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TRIAL COMES OUT, A LOT HAD TO DO

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CAN EMS CENTERS, WE'LL TALK

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ABOUT THAT IN A LITTLE BIT.

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NOVEL MCS DEVICES COME OUT IN

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THE MID 2000s AND THERE'S

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STILL A STAGNANT PERIOD.

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TRIALS COME OUT AND WE'LL TALK

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ABOUT THOSE IN A MINUTE.

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LOOKING AT THIS WITH A LITTLE

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MORE FIDELITY, LOOKING AT THE

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DIFFERENT TYPES OF CARDIOGENIC

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SHOCK, AGAIN YOU SEE THAT DROP

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IN MORTALITY IN THE EARLY

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2000s, FOLLOWED BY A PLATEAU,

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WITH A LITTLE BIT OF A POSSIBLE

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TREND TOWARDS IMPROVEMENT 2015

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TO 2018, WHICH WE'LL TALK ABOUT

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IN A FEW SLIDES.

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BUT THERE'S REALLY BEEN A REALLY

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STAGNANT PERIOD OVER THE LAST 20

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YEARS IN WHICH SCIENCE HAS

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EXPANDED, WE HAVE LOTS OF NEW

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TOOLS, MEDICAL CARE IN GENERAL

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HAS DRAMATICALLY IMPROVED ACROSS

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A NUMBER OF CONDITIONS.

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AND IN CARDIOLOGY, WE HAVE A

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MILLION NEW TECHNOLOGIES, BUT

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CARDIOGENIC SHOCK REALLY HAS NOT

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BENEFITED EVEN THOUGH WE

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THEORETICALLY CAN TREAT THE

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UNDERLYING CONDITIONS THAT DRIVE

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THIS STATE BETTER.

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SO THINKING ABOUT UNDERSTANDING

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WHY WE'RE NOT SEEING

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IMPROVEMENTS, IT'S BETTER TO GO

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BACK AND LOOK AT THE FAILURES OF

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EACH TRIAL.

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WE USE TO SUPPORT PATIENTS

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THROUGH THE BUMPS IN THE ROAD

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BUT WHEN YOU LOOK AT LONG TERM

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USE, PATIENTS DO NOT LIVE LONGER

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ON EYE ONOTROPES RELATIVE TO

254
00:09:04,395 --> 00:09:05,229
PLACEBO.

255
00:09:05,229 --> 00:09:09,533
IN YIF YOU LOOK AT THE DARK LINN

256
00:09:09,533 --> 00:09:11,402
ISCHEMIC PATIENTS, IT MAY

257
00:09:11,402 --> 00:09:15,006
ACCELERATE THEIR DEATH, SORT OF

258
00:09:15,006 --> 00:09:18,376
INTUITIVELY LIMITED.

259
00:09:18,376 --> 00:09:24,715
USING ROUTINE LINES IS SHOWN TO

260
00:09:24,715 --> 00:09:26,550
NOT IMPROVE MORTALITY AS WELL,

261
00:09:26,550 --> 00:09:28,786
ROUTINE USE, REALLY WANT TO

262
00:09:28,786 --> 00:09:31,522
HIGHLIGHT THAT WORD, ROUTINE USE

263
00:09:31,522 --> 00:09:34,458
OF BALLOON AND IMPELLA, NOT ABLE

264
00:09:34,458 --> 00:09:38,229
TO IMPROVE MORTALITY, EMPRESS IN

265
00:09:38,229 --> 00:09:38,629
2015.

266
00:09:38,629 --> 00:09:40,798
MOVING FORWARD, ECLS SHOCK MADE

267
00:09:40,798 --> 00:09:42,466
A SLASH BECAUSE EVERYBODY HAD

268
00:09:42,466 --> 00:09:44,535
BEEN ASSUMING ECMO WOULD BE THE

269
00:09:44,535 --> 00:09:45,970
HOLY GRAIL.

270
00:09:45,970 --> 00:09:47,805
ECMO ROUTINE USE, AGAIN, DID NOT

271
00:09:47,805 --> 00:09:49,940
IMPROVE MORTALITY IN AMI

272
00:09:49,940 --> 00:09:50,341
CARDIOGENIC SHOCK.

273
00:09:50,341 --> 00:09:51,442
I WOULD LIKE TO HIGHLIGHT THERE

274
00:09:51,442 --> 00:09:52,743
IS THIS LITTLE GAP YOU CAN SEE

275
00:09:52,743 --> 00:09:55,146
OUT TO DAY 14, WHERE THERE SEEMS

276
00:09:55,146 --> 00:09:56,447
TO BE A LITTLE BIT OF

277
00:09:56,447 --> 00:09:57,314
IMPROVEMENT IN SURVIVAL.

278
00:09:57,314 --> 00:09:58,949
IN THIS COHORT, THE PATIENTS

279
00:09:58,949 --> 00:10:01,919
DIED FROM REFRACTORY CARDIOGENIC

280
00:10:01,919 --> 00:10:02,119
SHOCK.

281
00:10:02,119 --> 00:10:03,120
SO IT'S REALLY IMPORTANT TO LOOK

282
00:10:03,120 --> 00:10:05,423
AT THIS DATA AND SAY WE DEPLOYED

283
00:10:05,423 --> 00:10:06,957
ECMO ON SOMEBODY WHO HAD A HEART

284
00:10:06,957 --> 00:10:08,492
ATTACK WHO HAD TERRIBLE HEART

285
00:10:08,492 --> 00:10:09,894
FAILURE, THEIR HEART NEVER GOT

286
00:10:09,894 --> 00:10:10,327
BETTER.

287
00:10:10,327 --> 00:10:13,964
THEN YOU START TO INTERPRET

288
00:10:13,964 --> 00:10:15,466
ECMO, ECMO DID NOT MAKE THE

289
00:10:15,466 --> 00:10:16,901
HEART BETTER.

290
00:10:16,901 --> 00:10:18,969
YOU HOPE THAT REVASCULARIZATION

291
00:10:18,969 --> 00:10:21,138
FOLLOWED BY GDMT OR TRANSPLANT

292
00:10:21,138 --> 00:10:23,140
OR LVAD WOULD BE YOUR ULTIMATE

293
00:10:23,140 --> 00:10:23,808
DESTINATION.

294
00:10:23,808 --> 00:10:25,776
AND THOSE WEREN'T DEPLOYED WITH

295
00:10:25,776 --> 00:10:27,411
FREQUENCY IN THIS TRIAL.

296
00:10:27,411 --> 00:10:28,946
TRYING TO UNDERSTAND SOME OF THE

297
00:10:28,946 --> 00:10:30,014
GAPS THAT THESE TRIALS ARE

298
00:10:30,014 --> 00:10:31,615
LEAVING OUT THERE FOR TREATMENT

299
00:10:31,615 --> 00:10:32,550
OPPORTUNITIES AND THINKING ABOUT

300
00:10:32,550 --> 00:10:35,286
HOW OTHER DATA INFORMS OUR CARE.

301
00:10:35,286 --> 00:10:36,387
DANGER SHOCK GAVE US A LITTLE

302
00:10:36,387 --> 00:10:40,858
BIT OF LIGHT AT THE END OF

303
00:10:40,858 --> 00:10:43,360
TRIAL, SHOWING MORTALITY BENEFIT

304
00:10:43,360 --> 00:10:44,929
AT AMI SHOCK, THE CURVES

305
00:10:44,929 --> 00:10:46,530
CONTINUE TO SEPARATE AT 180

306
00:10:46,530 --> 00:10:48,733
DAYS, SUGGESTING THAT EARLY

307
00:10:48,733 --> 00:10:49,834
INTERVENTIONS THAT OFFLOAD THE

308
00:10:49,834 --> 00:10:52,236
HEART MAY PROMOTE SURVIVAL AND

309
00:10:52,236 --> 00:10:53,537
MITIGATE END ORGAN INJURY THAT

310
00:10:53,537 --> 00:10:54,739
CONTRIBUTES TO BAD OUTCOMES

311
00:10:54,739 --> 00:10:55,473
LATER.

312
00:10:55,473 --> 00:10:57,908
THERE ARE ALSO -- OR IN THIS

313
00:10:57,908 --> 00:10:59,777
TRIAL, THE SUBTEXT IS IT TOOK 10

314
00:10:59,777 --> 00:11:01,746
YEARS TO ENROLL.

315
00:11:01,746 --> 00:11:03,380
AND THIS TRIAL FOCUSED ON A

316
00:11:03,380 --> 00:11:06,217
VERY, VERY, VERY SMALL FRACTION

317
00:11:06,217 --> 00:11:07,651
OF EVEN AMI SHOCK.

318
00:11:07,651 --> 00:11:09,854
SO WHEN WE LOOKED AT -- LOOK IN

319
00:11:09,854 --> 00:11:12,123
THE COHORT OF PATIENTS ABOUT

320
00:11:12,123 --> 00:11:13,324
40,000 PATIENTS, I APOLOGIZE FOR

321
00:11:13,324 --> 00:11:15,326
THE SMALL TEXT BUT WE STARTED

322
00:11:15,326 --> 00:11:16,527
WITH 20,000 SHOCK ADMISSIONS.

323
00:11:16,527 --> 00:11:18,062
AND WE ENDED UP SHOWING THAT

324
00:11:18,062 --> 00:11:22,733
ONLY ABOUT 30% OF ALL STEMI

325
00:11:22,733 --> 00:11:24,268
SHOCK AND ONLY 5% OF ALL

326
00:11:24,268 --> 00:11:26,804
CARDIOGENIC SHOCK IN OUR COHORT

327
00:11:26,804 --> 00:11:28,873
WOULD HAVE QUALIFIED FOR DANGER

328
00:11:28,873 --> 00:11:29,206
SHOCK.

329
00:11:29,206 --> 00:11:31,375
WHILE WE HAVE SOME DATA, THE

330
00:11:31,375 --> 00:11:34,211
VAST MAJORITY OF OUR PATIENTS DO

331
00:11:34,211 --> 00:11:36,547
NOT FALL UNDER THIS TRIAL.

332
00:11:36,547 --> 00:11:38,282
THERE'S LOTS OF PITFALLS WHERE

333
00:11:38,282 --> 00:11:39,917
IF WE START DEPLOYING INDIVIDUAL

334
00:11:39,917 --> 00:11:41,452
TECHNOLOGY AND TESTING THEM,

335
00:11:41,452 --> 00:11:42,753
WE'RE UNLIKELY TO DEMONSTRATE

336
00:11:42,753 --> 00:11:45,256
BENEFIT.

337
00:11:45,256 --> 00:11:47,558
SO IF WE REALLY WANT TO FIGURE

338
00:11:47,558 --> 00:11:49,193
OUT HOW TO CHANGE OUTCOMES IN

339
00:11:49,193 --> 00:11:50,060
CARDIOGENIC SHOCK I THINK YOU

340
00:11:50,060 --> 00:11:52,029
HAVE TO GO BACK TO THE DRAWING

341
00:11:52,029 --> 00:11:54,899
BOARD, REDIE FINE UNDERSTAND WHO

342
00:11:54,899 --> 00:11:57,401
THESE PATIENTS ARE, WHO ARE WE

343
00:11:57,401 --> 00:11:58,435
TREATING, HOW ARE WE TREATING

344
00:11:58,435 --> 00:11:59,270
THEM AND WHAT ARE THE THINGS

345
00:11:59,270 --> 00:12:00,471
THAT ARE SETTING THEM BACK.

346
00:12:00,471 --> 00:12:01,906
SO SHOCK IS VERY MUCH AN

347
00:12:01,906 --> 00:12:02,339
EVOLVING LANDSCAPE.

348
00:12:02,339 --> 00:12:03,741
WE CAN SEE INCIDENCE OF SHOCK IS

349
00:12:03,741 --> 00:12:04,775
GOING UP AND A LOT OF THAT HAS

350
00:12:04,775 --> 00:12:05,943
TO DO WITH THE FACT THAT PEOPLE

351
00:12:05,943 --> 00:12:07,812
ARE SURVIVING LONGER WITH HEART

352
00:12:07,812 --> 00:12:08,112
DISEASE.

353
00:12:08,112 --> 00:12:10,414
THIS POOL OF PATIENTS IS GETTING

354
00:12:10,414 --> 00:12:10,748
LARGER.

355
00:12:10,748 --> 00:12:12,483
THEY'RE GETTING OLDER.

356
00:12:12,483 --> 00:12:14,585
AND WE'RE ALSO SEEING -- AND IT

357
00:12:14,585 --> 00:12:16,420
HIGHLIGHTED BY THE FACT THAT

358
00:12:16,420 --> 00:12:17,755
NON-AMI CARDIOGENIC SHOCK IS THE

359
00:12:17,755 --> 00:12:19,056
FASTEST GROWING POPULATION HERE,

360
00:12:19,056 --> 00:12:20,591
AS WE TREAT CORONARY DISEASE,

361
00:12:20,591 --> 00:12:21,692
WE'RE MITIGATING HEART ATTACKS

362
00:12:21,692 --> 00:12:23,327
AND WE'RE SEEING MORE CHRONIC

363
00:12:23,327 --> 00:12:24,628
HEART DISEASE CONTRIBUTING TO

364
00:12:24,628 --> 00:12:27,064
THE SHOCK POPULATION.

365
00:12:27,064 --> 00:12:28,032
HERE IT'S DEMONSTRATING THAT AS

366
00:12:28,032 --> 00:12:28,365
WELL.

367
00:12:28,365 --> 00:12:30,601
YOU CAN XENON ISCHEMIC DISEASE

368
00:12:30,601 --> 00:12:32,937
AND ALSO CHRONIC ISCHEMIA, NOT

369
00:12:32,937 --> 00:12:36,240
ACUTE PLAQUE RUPTURE BUT CHRONIC

370
00:12:36,240 --> 00:12:38,042
ISCHEMIA, VERY DIFFERENT BEAST,

371
00:12:38,042 --> 00:12:39,710
IS A PRIMARY DRIVER OF

372
00:12:39,710 --> 00:12:40,945
CARDIOGENIC SHOCK IN MODERN

373
00:12:40,945 --> 00:12:41,245
COHORTS.

374
00:12:41,245 --> 00:12:42,680
IN ADDITION TO THAT, LOOKING AT

375
00:12:42,680 --> 00:12:44,114
MODERN CICU DATA, YOU CAN SEE

376
00:12:44,114 --> 00:12:45,850
THAT IT'S NOT JUST PURE

377
00:12:45,850 --> 00:12:46,650
CARDIOGENIC SHOCK THAT'S SHOWING

378
00:12:46,650 --> 00:12:47,918
UP IN ICU.

379
00:12:47,918 --> 00:12:49,153
SAY THESE PEOPLE ARE SHOWING UP

380
00:12:49,153 --> 00:12:50,654
AND IT THEIR HEART THAT'S THE

381
00:12:50,654 --> 00:12:51,655
PROBLEM FI THE HEART, THEY GO

382
00:12:51,655 --> 00:12:53,457
OUT THE DOOR, IS MISREPRESENTING

383
00:12:53,457 --> 00:12:53,958
THE ISSUE.

384
00:12:53,958 --> 00:12:55,259
FIRST, THE HEART DISEASE IS VERY

385
00:12:55,259 --> 00:12:56,026
DIVERSE.

386
00:12:56,026 --> 00:12:57,561
YOU CAN SEE THERE ON THE

387
00:12:57,561 --> 00:12:59,763
STATISTICS ON THE LEFT, ISOLATED

388
00:12:59,763 --> 00:13:01,065
LV FAILURE IS LESS THAN 50% OF

389
00:13:01,065 --> 00:13:03,901
THE COHORT.

390
00:13:03,901 --> 00:13:05,436
PULMONARY HYPERTENSION LEADING

391
00:13:05,436 --> 00:13:07,605
TO RV VAI YOU'RE IS TESTIMONY

392
00:13:07,605 --> 00:13:10,641
ALMOST 10% IN MODERN COHORTS.

393
00:13:10,641 --> 00:13:18,282
HEHEPPEF, TO SAY IS LV WORKING ,

394
00:13:18,282 --> 00:13:19,550
ARE WE GOING TO TRIAGE THE

395
00:13:19,550 --> 00:13:21,085
PERSON TO CARDIOLOGY OR AWAY,

396
00:13:21,085 --> 00:13:22,720
YOU'RE GOING TO MISS 10 TO 20%

397
00:13:22,720 --> 00:13:25,222
OF THESE PATIENT WHO HAVE LOW

398
00:13:25,222 --> 00:13:26,223
STROKE VOLUME WHERE THEIR

399
00:13:26,223 --> 00:13:27,091
PRIMARY PROBLEM IS ACTUALLY

400
00:13:27,091 --> 00:13:28,292
STEMMING FROM THEIR HEART MOST

401
00:13:28,292 --> 00:13:28,959
LIKELY.

402
00:13:28,959 --> 00:13:30,060
IN ADDITION I'D LIKE TO DRAW

403
00:13:30,060 --> 00:13:32,029
YOUR EYES HERE TO FIGURE A, AND

404
00:13:32,029 --> 00:13:33,964
YOU CAN SEE PURE CARDIOGENIC

405
00:13:33,964 --> 00:13:35,399
SHOCK IS ONLY TWO THIRDS OF THIS

406
00:13:35,399 --> 00:13:36,934
POPULATION.

407
00:13:36,934 --> 00:13:39,003
WITHIN THIS GROUP, MIXED SHOCK

408
00:13:39,003 --> 00:13:40,971
AND DISTRIBUTIVE SHOCK WHICH IS

409
00:13:40,971 --> 00:13:42,606
BOTH INFECTIOUS AND

410
00:13:42,606 --> 00:13:43,607
NON-INFECTIOUS DISTRIBUTIVE

411
00:13:43,607 --> 00:13:45,476
SHOCK IS A LARGE POOL AND THE

412
00:13:45,476 --> 00:13:46,543
HIGHEST RISK PORTION OF THIS

413
00:13:46,543 --> 00:13:47,444
COHORT.

414
00:13:47,444 --> 00:13:49,413
IT'S A DIFFERENT PHYSIOLOGY.

415
00:13:49,413 --> 00:13:52,349
SO MOVING FORWARD, WE CAN TALK

416
00:13:52,349 --> 00:13:53,450
ABOUT HOW THESE PATIENTS ARE

417
00:13:53,450 --> 00:13:54,652
GETTING OLDER, THEY'RE COMING IN

418
00:13:54,652 --> 00:13:55,953
WITH CHRONIC DISEASE.

419
00:13:55,953 --> 00:13:57,821
ONE THE OTHER THINGS THAT'S

420
00:13:57,821 --> 00:13:59,023
UNIQUE IN CARDIOGENIC SHOCK

421
00:13:59,023 --> 00:14:00,557
THAT'S VERY DIFFERENT FROM

422
00:14:00,557 --> 00:14:01,659
SEPTIC SHOCK, MOST OF THE TIMES

423
00:14:01,659 --> 00:14:03,093
WHEN PATIENTS HAVE SEPTIC SHOCK,

424
00:14:03,093 --> 00:14:05,262
ONCE THEY GET SEPTIC, THEIR PEAK

425
00:14:05,262 --> 00:14:06,030
DISEASE ASUPERVISING YOU HAVE

426
00:14:06,030 --> 00:14:08,098
THE RIGHT DRUG AND RIGHT BUG IS

427
00:14:08,098 --> 00:14:09,099
WITHIN 24 TO 48 HOURS.

428
00:14:09,099 --> 00:14:10,634
PATIENTS WHO ARE ADMITTED WITH

429
00:14:10,634 --> 00:14:11,735
CARDIOGENIC SHOCK, IF YOU LOOK

430
00:14:11,735 --> 00:14:16,206
AT THE TOP LEFT HERE, THE

431
00:14:16,206 --> 00:14:17,841
EARLIEST PHASES OF SHOCK BEING

432
00:14:17,841 --> 00:14:19,476
B, LATEST BEING E, IF YOU LOOK

433
00:14:19,476 --> 00:14:20,778
IN EACH OF THOSE CATEGORIES,

434
00:14:20,778 --> 00:14:22,446
THAT IS THE PERCENTAGE OF

435
00:14:22,446 --> 00:14:24,848
PATIENTS WHO ARE ADMITTED IN

436
00:14:24,848 --> 00:14:29,753
THAT THAT SCAI STAGE WHO GOT SIR

437
00:14:29,753 --> 00:14:30,421
DURING THEIR ADMISSION.

438
00:14:30,421 --> 00:14:32,289
IF YOU GO TO THE TOP RIGHT, THAT

439
00:14:32,289 --> 00:14:33,357
IS THE NUMBER OF HOURS IT TOOK

440
00:14:33,357 --> 00:14:34,792
THEM TO GO FROM THAT BASELINE

441
00:14:34,792 --> 00:14:38,729
STAGE TO A HIGHER SCAI SHOCK

442
00:14:38,729 --> 00:14:39,063
STAGE.

443
00:14:39,063 --> 00:14:40,597
YOU CAN SEE THE MAJORITY OF OUR

444
00:14:40,597 --> 00:14:42,032
PATIENTS ARE GETTING SICKER

445
00:14:42,032 --> 00:14:43,901
DESPITE MEDICAL ATTENTION, AND

446
00:14:43,901 --> 00:14:45,669
IT'S HAPPENING VERY LATE IN

447
00:14:45,669 --> 00:14:47,271
THEIR HOSPITAL PROCESS, WHICH IS

448
00:14:47,271 --> 00:14:48,572
SUGGESTING WE HAVE PATIENTS WITH

449
00:14:48,572 --> 00:14:50,975
CHRONIC DISEASE WHO ARE STARTING

450
00:14:50,975 --> 00:14:52,242
TO FAIL TRADITIONAL TREATMENT

451
00:14:52,242 --> 00:14:52,509
OPTIONS.

452
00:14:52,509 --> 00:14:54,712
SO YOU'RE STARTING TO MOVE INTO

453
00:14:54,712 --> 00:14:56,347
A REALLY COMPLICATED PHASE OF

454
00:14:56,347 --> 00:14:57,448
DISEASE WHERE ALL OF THINGS YOU

455
00:14:57,448 --> 00:14:59,083
WOULD REACH FOR THAT ARE

456
00:14:59,083 --> 00:15:00,284
STANDARD AREN'T WORKING.

457
00:15:00,284 --> 00:15:01,719
CARDIAC SURGERY, INTERVENTIONAL

458
00:15:01,719 --> 00:15:02,920
DEVICES AND THINGS OF THAT

459
00:15:02,920 --> 00:15:04,321
NATURE, WHEN YOU SEE PATIENTS

460
00:15:04,321 --> 00:15:05,656
PROGRESS, THEY DIE WITH A VERY

461
00:15:05,656 --> 00:15:06,390
HIGH FREQUENCY.

462
00:15:06,390 --> 00:15:07,725
SO ON THE LEFT THERE YOU'LL SEE

463
00:15:07,725 --> 00:15:10,694
THE BASELINE SCAI SHOCK STAGE.

464
00:15:10,694 --> 00:15:11,428
PROGRESSING TO THE RIGHT YOU'LL

465
00:15:11,428 --> 00:15:13,197
SEE THE PEAK.

466
00:15:13,197 --> 00:15:14,665
THE PERCENTAGE IN THE BOTTOM THE

467
00:15:14,665 --> 00:15:16,066
IN SINGLE COHORT IS MORTALITY

468
00:15:16,066 --> 00:15:17,568
ASSOCIATED WITH ACHIEVING THAT

469
00:15:17,568 --> 00:15:19,303
PEAK SKAI SHOCK STAGE.

470
00:15:19,303 --> 00:15:20,404
SO PROGRESSION IS INPATIENT.

471
00:15:20,404 --> 00:15:21,605
THESE ARE THE PATIENTS WE'RE

472
00:15:21,605 --> 00:15:22,072
LOSING.

473
00:15:22,072 --> 00:15:27,177
THE PATIENT  PATIENTS THAT GOT R

474
00:15:27,177 --> 00:15:28,278
WITH US AND THEN WE LOSE OUR

475
00:15:28,278 --> 00:15:29,279
OPPORTUNITY TO TREAT THEM.

476
00:15:29,279 --> 00:15:30,781
FURTHER HIGHLIGHTING THIS, THE

477
00:15:30,781 --> 00:15:31,548
CONTEMPORARY DRIVERS OF

478
00:15:31,548 --> 00:15:32,316
MORTALITY, YOU CAN SEE THE

479
00:15:32,316 --> 00:15:33,417
MAJORITY OF OUR PATIENTS EVEN

480
00:15:33,417 --> 00:15:34,618
THOUGH THEY'RE COMING IN WITH

481
00:15:34,618 --> 00:15:36,253
MIXED SHOCK AND ALL THIS

482
00:15:36,253 --> 00:15:37,254
COMPLICATED PHYSIOLOGY I SPOKE

483
00:15:37,254 --> 00:15:38,789
ABOUT, THE MAJORITY OF THEM DIE

484
00:15:38,789 --> 00:15:40,090
FROM REFRACTORY CARDIOGENIC

485
00:15:40,090 --> 00:15:40,657
SHOCK.

486
00:15:40,657 --> 00:15:42,826
SO WHEN YOU TALK IN A HOSPITAL

487
00:15:42,826 --> 00:15:43,494
POPULATION WHERE CAN YOU TAKE

488
00:15:43,494 --> 00:15:45,462
THEM TO SURGERY, YOU CAN

489
00:15:45,462 --> 00:15:47,297
TRANSPLANT THEM, TOTAL

490
00:15:47,297 --> 00:15:49,900
ARTIFICIAL HEART, LVAD, WE ARE

491
00:15:49,900 --> 00:15:50,934
LOSING PEOPLE BECAUSE THAT

492
00:15:50,934 --> 00:15:51,902
PRIMARY ORGAN WHERE WE HAVE ALL

493
00:15:51,902 --> 00:15:53,337
THESE THINGS TO OFFER CANNOT BE

494
00:15:53,337 --> 00:15:54,638
MODIFIED.

495
00:15:54,638 --> 00:15:56,273
SO WE REALLY GOT TO THINK WHY

496
00:15:56,273 --> 00:15:58,509
ARE WE LOSING THEMG, WHAT ARE

497
00:15:58,509 --> 00:16:00,511
THE THINGS THAT ARE MAKING THEM

498
00:16:00,511 --> 00:16:01,211
UNABLE TO TREAT THEM?

499
00:16:01,211 --> 00:16:03,047
ARE THEY TOO OLD, TOO SICK, ARE

500
00:16:03,047 --> 00:16:03,847
WE TOO LATE?

501
00:16:03,847 --> 00:16:05,582
WHAT ARE THOSE FEATURES?

502
00:16:05,582 --> 00:16:08,952
SO MOVING INTO -- IT'S A VERY

503
00:16:08,952 --> 00:16:10,054
COMPLEX PATIENT POPULATION.

504
00:16:10,054 --> 00:16:10,921
SO FIRST THINGS FIRST, WE'VE GOT

505
00:16:10,921 --> 00:16:12,156
TO GET EVERYBODY ON THE SAME

506
00:16:12,156 --> 00:16:13,323
PAGE.

507
00:16:13,323 --> 00:16:14,324
CRITICAL CARE DID THIS A LONG

508
00:16:14,324 --> 00:16:14,992
TIME AGO.

509
00:16:14,992 --> 00:16:17,327
SO WHEN YOU START TALKING ABOUT

510
00:16:17,327 --> 00:16:19,129
SOFA SCORE, SOME OF THE OTHER

511
00:16:19,129 --> 00:16:20,898
ACUTE CALCULATORS, PEOPLE

512
00:16:20,898 --> 00:16:22,099
FIGURED THIS OUT IN THE 2000s,

513
00:16:22,099 --> 00:16:23,400
WE HAVE TO HAVE SOMEBODY WHEN

514
00:16:23,400 --> 00:16:24,768
THEY HIT THE DOOR, WE KNOW HOW

515
00:16:24,768 --> 00:16:25,936
LIKELY YOU ARE TO NEED

516
00:16:25,936 --> 00:16:27,171
ESCALATION OF SERVICES AND WHAT

517
00:16:27,171 --> 00:16:28,972
YOU MAY NEED WHEN YOU GET TO OUR

518
00:16:28,972 --> 00:16:30,841
HOSPITAL.

519
00:16:30,841 --> 00:16:32,810
THAT HAS NOT BEEN TRUE IN

520
00:16:32,810 --> 00:16:35,312
CARDIOLOGY UNTIL 2019, WHEN SCAI

521
00:16:35,312 --> 00:16:37,081
SHOCK STAGES WAG DEVELOPED.

522
00:16:37,081 --> 00:16:38,916
IT USED TO BE YOU HAD TO GET TO

523
00:16:38,916 --> 00:16:44,288
THE CATH LAB, GET A LINE, OR GET

524
00:16:44,288 --> 00:16:45,823
AN ECHO TO QUANTIFY THE

525
00:16:45,823 --> 00:16:47,458
COMPROMISE OF YOUR CIRCULATORY

526
00:16:47,458 --> 00:16:47,791
SYSTEM.

527
00:16:47,791 --> 00:16:49,560
IT MADE IT VERY HARD TO ENTER A

528
00:16:49,560 --> 00:16:50,861
TREATMENT PATHWAY.

529
00:16:50,861 --> 00:16:52,830
SO SCAI STAGING BECAME A WAY TO

530
00:16:52,830 --> 00:16:54,031
START SAYING HOW SICK IS THIS

531
00:16:54,031 --> 00:16:54,465
PERSON?

532
00:16:54,465 --> 00:16:55,766
THIS HAS EVOLVED AND WE'RE NOT

533
00:16:55,766 --> 00:16:57,000
GOING TO GO THROUGH THE METRICS

534
00:16:57,000 --> 00:16:58,735
RIGHT NOW, BUT IT'S BEEN VERY

535
00:16:58,735 --> 00:16:59,837
WELL VALIDATED GOING FROM LEFT

536
00:16:59,837 --> 00:17:01,905
TO RIGHT, YOU SEE THE LOWER SKY

537
00:17:01,905 --> 00:17:03,540
STAGES AT B OR A, DEPENDING ON

538
00:17:03,540 --> 00:17:05,843
THE COHORT AND DARKER BLUE

539
00:17:05,843 --> 00:17:09,880
COLORS MOVING TO RIGHT BEING B.

540
00:17:09,880 --> 00:17:12,716
THE THINK ABOUT SCAI STAGING IS

541
00:17:12,716 --> 00:17:16,253
THIS IS CLINICIAN HA-DRIVEN,

542
00:17:16,253 --> 00:17:17,621
SOMEBODY WHO'S AN EXPERT LOOKING

543
00:17:17,621 --> 00:17:19,723
AT THE PATIENT SAYING YOU ARE

544
00:17:19,723 --> 00:17:21,058
THIS SICK.

545
00:17:21,058 --> 00:17:23,260
YOU WERE SAYING THIS VENTRICLE

546
00:17:23,260 --> 00:17:25,829
IS 9 CENTIMETERS SEVERELY

547
00:17:25,829 --> 00:17:28,265
DILATED, YOUR LACTATE COULD BE F

548
00:17:28,265 --> 00:17:28,565
DEATH.

549
00:17:28,565 --> 00:17:29,900
SO THAT STARTS TO CAPTURE THESE

550
00:17:29,900 --> 00:17:31,301
PATIENTS WHO ARE REALLY, REALLY

551
00:17:31,301 --> 00:17:32,636
SICK AND NEED AN ESCALATION OF

552
00:17:32,636 --> 00:17:34,505
CARE THAT MIGHT NOT BE OBVIOUS

553
00:17:34,505 --> 00:17:36,006
BY THE NUMBERS THAT YOU'RE

554
00:17:36,006 --> 00:17:38,075
PRESENTED IN EMR.

555
00:17:38,075 --> 00:17:39,843
SO HOW DOES THIS GET DEPLOYED IN

556
00:17:39,843 --> 00:17:41,145
EXPERT CENTERS?

557
00:17:41,145 --> 00:17:43,213
SO PEOPLE DEVELOPED SHOCK TEAMS

558
00:17:43,213 --> 00:17:44,214
BECAUSE WHAT BECAME REALLY CLEAR

559
00:17:44,214 --> 00:17:45,649
IS IT'S VERY HARD TO GET

560
00:17:45,649 --> 00:17:46,316
PEOPLE'S ATTENTION.

561
00:17:46,316 --> 00:17:48,285
IT'S HARD TO GET ENOUGH DATA IN

562
00:17:48,285 --> 00:17:50,220
A TIMELY FASHION TO GET A

563
00:17:50,220 --> 00:17:52,089
CARDIOLOGIST TO BEDSIDE OR AN

564
00:17:52,089 --> 00:17:53,957
APPROPRIATE PERSON TO RESPOND TO

565
00:17:53,957 --> 00:17:55,058
THESE PATIENTS TO ESCALATE CARE.

566
00:17:55,058 --> 00:17:56,693
SO WE CREATED SHOCK TEAMS.

567
00:17:56,693 --> 00:17:58,495
WHAT THEY DID IS YOU NOTICE HERE

568
00:17:58,495 --> 00:17:59,429
RATHER THAN IN THE INITIAL

569
00:17:59,429 --> 00:18:00,731
TRIALS WHICH WE DIDN'T SHARE,

570
00:18:00,731 --> 00:18:03,133
BUT THEY DIDN'T CREATE COMPLEX

571
00:18:03,133 --> 00:18:04,401
CRITERIA TO GET THEIR ATTENTION.

572
00:18:04,401 --> 00:18:06,203
YOU DIDN'T HAVE TO HAVE A

573
00:18:06,203 --> 00:18:07,304
CARDIAC INDEX ESTIMATED.

574
00:18:07,304 --> 00:18:08,739
YOU DON'T HAVE TO HAVE A WEDGE

575
00:18:08,739 --> 00:18:09,006
MEASURED.

576
00:18:09,006 --> 00:18:10,040
BUT THEY SAID IF YOU THINK THE

577
00:18:10,040 --> 00:18:12,776
HEART IS INVOLVED AND YOU'RE

578
00:18:12,776 --> 00:18:13,977
HYPOTENSIVE AND THE PESH IS

579
00:18:13,977 --> 00:18:16,713
MAKING LACTATE, CALL US.

580
00:18:16,713 --> 00:18:18,715
THEY MADE 24/7 RESPONSE SYSTEMS,

581
00:18:18,715 --> 00:18:20,517
AND THEN THEY CREATED CARE TEAMS

582
00:18:20,517 --> 00:18:21,952
WITH PROTOCOLIZED ASSESSMENTS.

583
00:18:21,952 --> 00:18:23,153
SO THEY SAID WE ARE ALL GOING TO

584
00:18:23,153 --> 00:18:26,423
COME IN, WE'RE GOING TO DO X, Y

585
00:18:26,423 --> 00:18:27,324
AND Z AND AT THE END OF THIS

586
00:18:27,324 --> 00:18:28,759
WE'RE GOING TO HAVE AN AGREED

587
00:18:28,759 --> 00:18:30,160
UPON ESCALATION STRATEGY OF HOW

588
00:18:30,160 --> 00:18:31,361
WE'RE GOING TO THINK THROUGH

589
00:18:31,361 --> 00:18:32,563
DEVICES, WHAT WE NEED TO DO FOR

590
00:18:32,563 --> 00:18:34,531
THIS PATIENT AND WE'RE GOING TO

591
00:18:34,531 --> 00:18:35,065
MOVE EXPEDITIOUSLY.

592
00:18:35,065 --> 00:18:36,300
WE'RE NOT GOING TO SECOND-GUESS

593
00:18:36,300 --> 00:18:37,801
EACH OTHER, WE'RING GO TO HAVE A

594
00:18:37,801 --> 00:18:39,236
GROUP DISCUSSION, COLLABORATIVE

595
00:18:39,236 --> 00:18:40,904
CARE MODEL AND MOVE THIS PATIENT

596
00:18:40,904 --> 00:18:41,538
FORWARD.

597
00:18:41,538 --> 00:18:42,506
REALLY IMPORTANTLY THERE'S

598
00:18:42,506 --> 00:18:43,273
CONTINUED ASSESSMENT.

599
00:18:43,273 --> 00:18:44,608
SO THIS TEAM STAYED INVOLVED AND

600
00:18:44,608 --> 00:18:45,242
THEY'RE IN CHARGE OF THE

601
00:18:45,242 --> 00:18:45,676
PATIENT.

602
00:18:45,676 --> 00:18:47,344
BECAUSE EVERYTHING YOU DO IN AN

603
00:18:47,344 --> 00:18:48,312
ICU HAS CONSEQUENCES.

604
00:18:48,312 --> 00:18:49,613
SO IT'S REALLY IMPORTANT WHILE

605
00:18:49,613 --> 00:18:50,581
YOU'RE ADDING THINGS, YOU HAVE

606
00:18:50,581 --> 00:18:52,349
TO TAKE THAT THERAPY AWAY AS

607
00:18:52,349 --> 00:18:53,550
QUICKLY AS YOU CAN, AND IF YOU

608
00:18:53,550 --> 00:18:54,885
CAN'T TAKE IT AWAY, YOU HAVE TO

609
00:18:54,885 --> 00:18:57,821
MOVE THAT PERSON DOWN TO A

610
00:18:57,821 --> 00:18:59,156
DEFINITIVE CARE PATHWAY SO

611
00:18:59,156 --> 00:19:00,557
THEY'RE NOT EXPOSED TO SIDE

612
00:19:00,557 --> 00:19:01,892
EFFECT OF THAT DEVICE, BREATHING

613
00:19:01,892 --> 00:19:03,427
TUBE, WHAT HAVE YOU THAT

614
00:19:03,427 --> 00:19:04,494
PRECLUDE YOU FROM MOVING

615
00:19:04,494 --> 00:19:05,062
FORWARD.

616
00:19:05,062 --> 00:19:06,697
THESE ARE SOME OF MY FAVORITE

617
00:19:06,697 --> 00:19:07,764
PIECES OF DATA.

618
00:19:07,764 --> 00:19:09,967
THERE'S VALIDITY ISSUES THAT

619
00:19:09,967 --> 00:19:11,168
PEOPLE ARGUE WITH, BUT THREE

620
00:19:11,168 --> 00:19:13,370
TRIALS CAME OUT NP A TWO-YEAR

621
00:19:13,370 --> 00:19:15,105
PERIOD.

622
00:19:15,105 --> 00:19:16,540
FROM THREE DIFFERENT CENTERS.

623
00:19:16,540 --> 00:19:19,810
ALL OF THEM COMPARED THEIR

624
00:19:19,810 --> 00:19:21,111
OUTCOMES FROM THE SHOCK TEAM TO

625
00:19:21,111 --> 00:19:24,514
TWO TO THREE YEARS PRECEDING.

626
00:19:24,514 --> 00:19:26,283
NONE HAD NEW ATTENDINGS, NONE

627
00:19:26,283 --> 00:19:27,017
HAD NEW DEVICES.

628
00:19:27,017 --> 00:19:29,119
THERE WERE NO MAJOR MEDICAL

629
00:19:29,119 --> 00:19:30,420
ADVANCES IN THE TIME PERIOD IN

630
00:19:30,420 --> 00:19:32,389
WHICH THESE STUDIES WERE DONE.

631
00:19:32,389 --> 00:19:34,891
AND ALL THREE OUTCOMES IMPROVED

632
00:19:34,891 --> 00:19:36,226
MORTALITY BY ALMOST IDENTICAL

633
00:19:36,226 --> 00:19:37,761
AMOUNTS.

634
00:19:37,761 --> 00:19:39,830
AND WHAT THEY SHOWED IS THAT BY

635
00:19:39,830 --> 00:19:41,898
OPTIMIZING YOUR CARE PATHWAY,

636
00:19:41,898 --> 00:19:43,734
DEPLOYING MEDICAL KNOWLEDGE THAT

637
00:19:43,734 --> 00:19:46,403
MOST OF US KNOW, WE ALL READ THE

638
00:19:46,403 --> 00:19:49,306
SAME TEXTBOOKS, AND WE WORK AS A

639
00:19:49,306 --> 00:19:50,974
TEAM, WE'RE ABLE TO DROP MORTAL

640
00:19:50,974 --> 00:19:52,175
PRETTY SIGNIFICANTLY AND

641
00:19:52,175 --> 00:19:52,509
REPRODUCIBLY.

642
00:19:52,509 --> 00:19:54,478
WHEN YOU LOOK AT THIS IN A

643
00:19:54,478 --> 00:19:57,047
LARGER COHORT, CHRIS WAS ONE OF

644
00:19:57,047 --> 00:19:59,082
THE -- WAS THE LEAD -- OR WAS

645
00:19:59,082 --> 00:20:00,083
THE SENIOR AUTHOR IN THE STUDY,

646
00:20:00,083 --> 00:20:02,586
THIS IS FROM OUR CRITICAL CARE

647
00:20:02,586 --> 00:20:04,988
CARDIOLOGY NETWORK, AGAIN,

648
00:20:04,988 --> 00:20:06,423
20,000 SHOCK ADMISSIONS, AND

649
00:20:06,423 --> 00:20:07,357
ACTUALLY THIS WAS BEFORE, THIS

650
00:20:07,357 --> 00:20:08,592
WAS A FEW YEARS AGO, A LITTLE

651
00:20:08,592 --> 00:20:09,793
BIT SMALLER COHORT.

652
00:20:09,793 --> 00:20:11,428
THEY LOOKED AT CENTERS WITH AND

653
00:20:11,428 --> 00:20:12,629
WITHOUT SHOCK TEAMS.

654
00:20:12,629 --> 00:20:14,398
AND THEY WERE ABLE TO SHOW THAT

655
00:20:14,398 --> 00:20:16,700
THERE WAS REDUCED MORTALITY, AND

656
00:20:16,700 --> 00:20:18,068
REALLY IMPORTANTLY, THERE WAS

657
00:20:18,068 --> 00:20:20,837
EARLY PAUs, PA CATHETER USE,

658
00:20:20,837 --> 00:20:22,939
BUT DIRECTED PA CATHETER USE, SO

659
00:20:22,939 --> 00:20:24,474
IT WAS USED MORE FREQUENTLY AND

660
00:20:24,474 --> 00:20:24,708
EARLIER.

661
00:20:24,708 --> 00:20:27,511
THEY ENDED UP USING LESS OVERALL

662
00:20:27,511 --> 00:20:30,147
MCS BUT MORE ADVANCED MCS.

663
00:20:30,147 --> 00:20:35,619
WHAT THAT MEANS, -- BALLOON PUMP

664
00:20:35,619 --> 00:20:37,154
GENERALLY LESS EFFECTIVE IN

665
00:20:37,154 --> 00:20:38,455
PEOPLE IN SIGNIFICANT SHOCK.

666
00:20:38,455 --> 00:20:40,290
HAS A ROLE BUT NOT A UBIQUITOUS

667
00:20:40,290 --> 00:20:40,657
TREATMENT.

668
00:20:40,657 --> 00:20:44,895
AND THEY FAVOR MORE IMPELLA,

669
00:20:44,895 --> 00:20:46,229
TANDEM AND ECHO TO FULLY TAKE

670
00:20:46,229 --> 00:20:47,531
OVER SOMEBODY'S CIRCULATORY

671
00:20:47,531 --> 00:20:48,732
SUPPORT AND THOSE THINGS SEEM TO

672
00:20:48,732 --> 00:20:50,500
BE ASSOCIATED WITH IMPROVED

673
00:20:50,500 --> 00:20:50,767
SURVIVAL.

674
00:20:50,767 --> 00:20:52,336
BUT AGAIN, COMPLEX CARE TEAMS

675
00:20:52,336 --> 00:20:53,103
AND THERE'S REQUIREMENTS THAT

676
00:20:53,103 --> 00:20:54,371
THIS IS NOT JUST ONE PERSON

677
00:20:54,371 --> 00:20:56,406
COMING IN, THIS IS A TEAM-BASED

678
00:20:56,406 --> 00:21:00,210
APPROACH.

679
00:21:00,210 --> 00:21:01,311
IN THIS SAME PERIOD OF TIME

680
00:21:01,311 --> 00:21:02,579
YOU'VE SEEN EXPANSION IN THE

681
00:21:02,579 --> 00:21:04,715
UNITED STATES IN USE OF

682
00:21:04,715 --> 00:21:05,382
TEMPORARY MCS.

683
00:21:05,382 --> 00:21:11,154
SO MORE ECHO AND IMPE LA AND

684
00:21:11,154 --> 00:21:12,923
TANDEM HEART, LESS BALLOON PUMP.

685
00:21:12,923 --> 00:21:14,758
YOU LOOK AT TWO COUNTRIES, WE

686
00:21:14,758 --> 00:21:16,026
HAVE CANADIAN PARTNERS, SO THESE

687
00:21:16,026 --> 00:21:17,828
ARE PEER INSTITUTIONS LOOKING IN

688
00:21:17,828 --> 00:21:20,897
THE SAME PERIOD OF TIME.

689
00:21:20,897 --> 00:21:25,802
PER SCAI SHOCK STAGE, IN RED THE

690
00:21:25,802 --> 00:21:26,703
CANADIAN MORTALITY, IN BLUE THE

691
00:21:26,703 --> 00:21:27,037
U.S.

692
00:21:27,037 --> 00:21:28,939
IT SEEMS THAT THE U.S. OUTCOMES

693
00:21:28,939 --> 00:21:32,309
IN MATCHED CASES SEEM TO BE

694
00:21:32,309 --> 00:21:32,876
BETTER.

695
00:21:32,876 --> 00:21:34,177
QUESTION, WHAT IS DRIVING THIS?

696
00:21:34,177 --> 00:21:35,278
AGAIN THESE ARE ALL ASSOCIATIONS

697
00:21:35,278 --> 00:21:36,480
SO WE HAVE TO BE REALLY CAREFUL,

698
00:21:36,480 --> 00:21:43,153
BUT AGAIN, THIS THEME OF MORTEME

699
00:21:43,153 --> 00:21:46,890
TEMPORARY MCS, MORE PRECISE

700
00:21:46,890 --> 00:21:47,791
DIAGNOSES THAT GUIDE YOUR

701
00:21:47,791 --> 00:21:48,658
THERAPIES SEEM TO BE A THEME

702
00:21:48,658 --> 00:21:49,326
HERE AS WELL.

703
00:21:49,326 --> 00:21:50,627
HERE YOU CAN LOOK AT A

704
00:21:50,627 --> 00:21:52,262
DISTRIBUTION OF THE DEVICES YOU

705
00:21:52,262 --> 00:21:52,596
USE.

706
00:21:52,596 --> 00:21:54,664
IN CANADA, AGAIN, MUCH MORE

707
00:21:54,664 --> 00:21:56,867
BALLOON PUMP, MUCH LESS ADVANCED

708
00:21:56,867 --> 00:21:57,868
MCS.

709
00:21:57,868 --> 00:22:02,072
SO WE STARTED SAYING HOW CAN

710
00:22:02,072 --> 00:22:03,407
WE -- CAN WE EXPERIENCE THESE

711
00:22:03,407 --> 00:22:04,474
OUTCOMES BEYOND THESE CENTERS?

712
00:22:04,474 --> 00:22:10,080
IN THE U.S., THERE'S -- WE DON'T

713
00:22:10,080 --> 00:22:12,916
HAVE UBIQUITOUS ACCESS TO

714
00:22:12,916 --> 00:22:13,450
SPECIALISTS.

715
00:22:13,450 --> 00:22:14,217
PEOPLE CROSS TRAINED,

716
00:22:14,217 --> 00:22:17,287
ENVIRONMENTS THAT CAN SUPPORT

717
00:22:17,287 --> 00:22:18,722
ALL OF OUR CAREERS SO WE HAVE

718
00:22:18,722 --> 00:22:20,223
TIME TO ALL SHARE OUR EXPERTISE.

719
00:22:20,223 --> 00:22:21,391
A LOT OF PEOPLE ARE WORKING OUT

720
00:22:21,391 --> 00:22:25,061
IN THE COMMUNITY.

721
00:22:25,061 --> 00:22:26,797
AND INOVA WAS ABLE TO

722
00:22:26,797 --> 00:22:29,433
DEMONSTRATE THAT BY CREATING A

723
00:22:29,433 --> 00:22:30,634
SHOCK PROTOCOL, THEY WERE ABLE

724
00:22:30,634 --> 00:22:32,235
TO EXPERIENCE SIMILAR OUTCOMES

725
00:22:32,235 --> 00:22:33,670
REGARDLESS OF WHERE THEIR

726
00:22:33,670 --> 00:22:35,338
PATIENTS PRESENTED.

727
00:22:35,338 --> 00:22:37,407
SO NOW ALL OF A SUDDEN YOU START

728
00:22:37,407 --> 00:22:40,677
TO SAY OH HE KAY, WE HAVE THIS

729
00:22:40,677 --> 00:22:42,145
COMPLEX PATIENT, IF WE ESCALATE

730
00:22:42,145 --> 00:22:43,413
THEM QUICKLY, WE CAN GET THE

731
00:22:43,413 --> 00:22:44,514
SAME OUTCOMES.

732
00:22:44,514 --> 00:22:47,017
BUT INOVA WORKS IN A 10,000

733
00:22:47,017 --> 00:22:48,251
SQUARE MILE AREA.

734
00:22:48,251 --> 00:22:51,521
THIS IS WHERE I WORK.

735
00:22:51,521 --> 00:22:52,355
FREUCIAL RATHER THAN HAVING A

736
00:22:52,355 --> 00:22:53,590
SMALL NUMBER OF INSURANCE

737
00:22:53,590 --> 00:22:57,828
SYSTEMS, WE HAVE 58 COUNTY, A

738
00:22:57,828 --> 00:22:59,296
BUNCH OF DIFFERENT INSURANCE

739
00:22:59,296 --> 00:23:00,597
SYSTEMS, A TON OF AMBULANCE

740
00:23:00,597 --> 00:23:01,998
SYSTEMS TO WORK WITH AND FOR

741
00:23:01,998 --> 00:23:03,700
ADVANCED THERAPIES, WE HAVE ONE

742
00:23:03,700 --> 00:23:04,534
COMPANY TO TRANSPORT IN

743
00:23:04,534 --> 00:23:04,968
CALIFORNIA.

744
00:23:04,968 --> 00:23:06,369
NOW IT'S UP TO TWO.

745
00:23:06,369 --> 00:23:07,704
BUT STILL, NOT VERY MUCH.

746
00:23:07,704 --> 00:23:09,573
AND IF YOU LOOK AT THIS MAP, WE

747
00:23:09,573 --> 00:23:11,641
JUST DEVELOPED -- THIS IS STILL

748
00:23:11,641 --> 00:23:13,510
A ROUGH ESTIMATE, BUT FROM A

749
00:23:13,510 --> 00:23:16,346
SURVEY STUDY, RED IS LEVEL

750
00:23:16,346 --> 00:23:17,280
1CICUs, BLUE IS LEVEL 2.

751
00:23:17,280 --> 00:23:18,748
THIS IS THE HOSPITALS IN

752
00:23:18,748 --> 00:23:20,617
CALIFORNIA FROM OUR SURVEY STUDY

753
00:23:20,617 --> 00:23:22,586
THAT ARE -- OR THE POPULATION OF

754
00:23:22,586 --> 00:23:24,221
CALIFORNIA WITHIN 30 MINUTES OF

755
00:23:24,221 --> 00:23:25,956
A HOSPITAL DESCRIBED AT ONE OF

756
00:23:25,956 --> 00:23:28,158
THOSE CICU LEVELS.

757
00:23:28,158 --> 00:23:30,360
SO ENORMOUS, ENORMOUS GAPS IN

758
00:23:30,360 --> 00:23:31,661
CARE AND ABILITY TO GET PATIENTS

759
00:23:31,661 --> 00:23:35,065
TO PLACES IN THE RIGHT AMOUNT OF

760
00:23:35,065 --> 00:23:37,033
TIME.

761
00:23:37,033 --> 00:23:38,235
AND STAFFING REALLY MATTERS.

762
00:23:38,235 --> 00:23:39,836
WHEN YOU LOOK AT STUDIES, YOU

763
00:23:39,836 --> 00:23:42,038
LOOK AT CICUs, HIGH INTENSITY

764
00:23:42,038 --> 00:23:44,374
AND SPECIALTY TRAINED CICUs

765
00:23:44,374 --> 00:23:45,442
HAVE LOWER MORTALITY, BOTH

766
00:23:45,442 --> 00:23:47,410
HOSPITAL AND CICU MORTALITY, AND

767
00:23:47,410 --> 00:23:48,945
IT'S IMPORTANT -- IT'S NOT THAT

768
00:23:48,945 --> 00:23:50,814
THE CARDIAC DIAGNOSES BENEFIT.

769
00:23:50,814 --> 00:23:52,349
IT'S THE EXTRA CARDIAC

770
00:23:52,349 --> 00:23:53,917
COMPLICATIONS OF CARDIOVASCULAR

771
00:23:53,917 --> 00:23:55,519
DISEASE THAT SEEM TO BENEFIT

772
00:23:55,519 --> 00:23:58,054
PRIMARILY FROM THIS EXTRA

773
00:23:58,054 --> 00:23:59,756
TRAINING AND FOR A LOT OF

774
00:23:59,756 --> 00:24:00,857
INTENSIVISTS IN THE ROOM, IT'S

775
00:24:00,857 --> 00:24:02,626
MAKING SURE UR DOING THE EVENT

776
00:24:02,626 --> 00:24:04,160
RIGHT, NOT INJURING LUNG,

777
00:24:04,160 --> 00:24:04,694
REPLACEMENT THERAPY DONE

778
00:24:04,694 --> 00:24:05,028
PROPERLY.

779
00:24:05,028 --> 00:24:06,763
I MEAN, REALLY CAUTIOUS WITH

780
00:24:06,763 --> 00:24:07,664
YOUR MULTI-DISCIPLINARY CARE.

781
00:24:07,664 --> 00:24:10,700
AND AGAIN, IF YOU LOOK AT HIGH

782
00:24:10,700 --> 00:24:13,870
AND LOW INTENSITY STAFFING AT

783
00:24:13,870 --> 00:24:14,971
CICUs, YOU SEE NOT ONLY THAT

784
00:24:14,971 --> 00:24:16,840
SPECIALTY TRAINING BUT ALSO THE

785
00:24:16,840 --> 00:24:18,041
INTENSIVITY OF STAFFING, HAVING

786
00:24:18,041 --> 00:24:19,576
YOUR OWN PHARMACISTS, SPECIALLY

787
00:24:19,576 --> 00:24:21,845
TRAINED NURSES, RTs, PHYSICAL

788
00:24:21,845 --> 00:24:22,712
THERAPISTS, THOSE ALL CONTRIBUTE

789
00:24:22,712 --> 00:24:26,583
TO PEN F BENEFIT AND THEY SEEM O

790
00:24:26,583 --> 00:24:29,986
BENEFIT MOSTLY THE -- DAYS ON

791
00:24:29,986 --> 00:24:32,455
THE VENTILATOR.

792
00:24:32,455 --> 00:24:33,690
PROBLEM IN THE U.S. IS THIS IS

793
00:24:33,690 --> 00:24:35,425
NOT A COMMON PRACTICE PARADIGM.

794
00:24:35,425 --> 00:24:41,298
THE MAJORITY OF OU ICUs IN THE

795
00:24:41,298 --> 00:24:43,199
UNITED STATES ARE OPEN ICU

796
00:24:43,199 --> 00:24:44,601
MODEL, MEANING SOMEBODY WHO IS

797
00:24:44,601 --> 00:24:45,969
NOT GEOGRAPHICALLY LOCATED IN

798
00:24:45,969 --> 00:24:47,604
ICU FOR THEIR PRACTICE IS

799
00:24:47,604 --> 00:24:48,972
ADMITTING PATIENTS IN AND MAYBE

800
00:24:48,972 --> 00:24:50,640
COMANAGING WITH AN INTENSIVIST.

801
00:24:50,640 --> 00:24:51,541
IN ADDITION GOING ALL THE WAY TO

802
00:24:51,541 --> 00:24:52,609
THE RIGHT, YOU CAN SEE THE

803
00:24:52,609 --> 00:24:54,244
NUMBER OF CICUs THAT ARE

804
00:24:54,244 --> 00:24:55,645
STAFFED WITH PEOPLE WHO ARE DUAL

805
00:24:55,645 --> 00:24:57,514
TRAINED IN CARDIOLOGY AND

806
00:24:57,514 --> 00:24:58,915
INTENSIVE CARE.

807
00:24:58,915 --> 00:25:03,219
THIS IS A RARE RESOURCE, AND WE

808
00:25:03,219 --> 00:25:04,521
ARE NOT SET UP IDEALLY TO

809
00:25:04,521 --> 00:25:06,156
DELIVER CARE AND FOLLOW THE DATA

810
00:25:06,156 --> 00:25:07,591
THAT SEEMS TO BE ASSOCIATED WITH

811
00:25:07,591 --> 00:25:09,659
IMPROVED OUTCOMES IN CARDIOGENIC

812
00:25:09,659 --> 00:25:11,094
SHOCK.

813
00:25:11,094 --> 00:25:12,729
SO BIOMARKERS BECOME A VERY

814
00:25:12,729 --> 00:25:14,364
INTUITIVE TOOL HERE WHERE YOU

815
00:25:14,364 --> 00:25:15,999
WANT TO START SAYING WE NEED TO

816
00:25:15,999 --> 00:25:17,000
IDENTIFY THESE PATIENTS EARLIER,

817
00:25:17,000 --> 00:25:18,068
MOVE THEM TO THE RIGHT PLACE SO

818
00:25:18,068 --> 00:25:20,704
THEY CAN STILL BENEFIT FROM

819
00:25:20,704 --> 00:25:21,237
THERAPY.

820
00:25:21,237 --> 00:25:23,673
HOW DO BIOMARKERS FIT INTO THIS

821
00:25:23,673 --> 00:25:24,107
PARADIGM?

822
00:25:24,107 --> 00:25:27,377
FIRST BEFORE WE GET INTO THESE

823
00:25:27,377 --> 00:25:28,144
BIOMARKER SPECIALTY

824
00:25:28,144 --> 00:25:29,346
DESCRIPTIONS, WE REALLY WANT TO

825
00:25:29,346 --> 00:25:30,547
UNDERSTAND WHAT ARE THE

826
00:25:30,547 --> 00:25:31,548
BIOCHEMICAL PROFILES WE WANT TO

827
00:25:31,548 --> 00:25:32,248
TARGET?

828
00:25:32,248 --> 00:25:33,717
TAKING ALL OF OUR LESSONS FROM

829
00:25:33,717 --> 00:25:34,651
THE TRIALS WE TALKED ABOUT IN

830
00:25:34,651 --> 00:25:36,119
THE BEGINNING, IT'S A MISTAKE TO

831
00:25:36,119 --> 00:25:37,921
GO INTO CARDIOGENIC SHOCK AND

832
00:25:37,921 --> 00:25:40,824
SAY WE ARE GOING TO TAKE THIS

833
00:25:40,824 --> 00:25:41,825
AND JUST GO BOOM.

834
00:25:41,825 --> 00:25:42,592
YOU WILL FAIL.

835
00:25:42,592 --> 00:25:43,693
THESE PATIENTS ARE ALL VERY

836
00:25:43,693 --> 00:25:45,762
COMPLICATED AND THE MOST

837
00:25:45,762 --> 00:25:47,497
SUCCESSFUL SHOCK TRIAL WE HAD

838
00:25:47,497 --> 00:25:49,599
WAS DANGER SHOCK WHICH TOOK 10

839
00:25:49,599 --> 00:25:50,700
YEARS TO ENROLL.

840
00:25:50,700 --> 00:25:52,869
SO HOW DO WE GET TARGETED, HOW

841
00:25:52,869 --> 00:25:55,372
DO WE BENEFIT THESE PATIENTS WHO

842
00:25:55,372 --> 00:25:55,939
MAY BENEFIT?

843
00:25:55,939 --> 00:25:58,341
FIRST YOU WANT TO UNDERSTAND

844
00:25:58,341 --> 00:25:59,442
PARTICIPATING PROGRESSION TO

845
00:25:59,442 --> 00:26:00,176
UNDERSTAND WHO HAS THE

846
00:26:00,176 --> 00:26:02,479
OPPORTUNITY TO BENEFIT.

847
00:26:02,479 --> 00:26:04,047
SOME OF THE EARLY WORK, YOU CAN

848
00:26:04,047 --> 00:26:06,216
SEE HERE THREE PROPOSED PROFILES

849
00:26:06,216 --> 00:26:07,617
FOR CARDIOGENIC SHOCK.

850
00:26:07,617 --> 00:26:08,985
ON THE LEFT, WE DON'T HAVE TO GO

851
00:26:08,985 --> 00:26:10,387
THROUGH ALL THE DATA THERE, BUT

852
00:26:10,387 --> 00:26:12,555
IT'S ESSENTIALLY LOW OUTPUT, NO

853
00:26:12,555 --> 00:26:14,190
SYSTEMIC ACIDOSIS AND LIMITED

854
00:26:14,190 --> 00:26:15,492
SYSTEMIC CONGESTION.

855
00:26:15,492 --> 00:26:18,028
MOVING TO THE MIDDLE, YOU SEE

856
00:26:18,028 --> 00:26:19,562
THE CARD YAL RENAL SYSTEM WHERE

857
00:26:19,562 --> 00:26:21,398
YOU'VE MOVED INTO LOW OUTPUT BUT

858
00:26:21,398 --> 00:26:24,234
ALSO YOU HAVE CONGESTION AND

859
00:26:24,234 --> 00:26:28,405
PRIMARILY CONGESTIVE MARKERS,

860
00:26:28,405 --> 00:26:29,072
BILIRUBIN.

861
00:26:29,072 --> 00:26:32,342
THE THIRD IS CARDIOMETABOLIC

862
00:26:32,342 --> 00:26:34,878
CACARDIOGENIC SHOCK.

863
00:26:34,878 --> 00:26:36,413
YOU ALSO HAVE CELLULAR ACIDOSIS

864
00:26:36,413 --> 00:26:37,080
SETTING IN.

865
00:26:37,080 --> 00:26:38,548
WHEN YOU LOOK AT THE OUTCOMES

866
00:26:38,548 --> 00:26:40,016
ASSOCIATED WITH THESE THREE

867
00:26:40,016 --> 00:26:40,917
PHENOTYPES, BY THE TIME YOU MOVE

868
00:26:40,917 --> 00:26:42,318
INTO THIS ACIDOSIS STATE, YOU

869
00:26:42,318 --> 00:26:43,753
HAVE VERY, VERY, VERY POOR

870
00:26:43,753 --> 00:26:44,621
OUTCOMES.

871
00:26:44,621 --> 00:26:47,891
AND IF YOU LOOK AT HOW MCS WORKS

872
00:26:47,891 --> 00:26:50,093
IN THESE PATIENTS, YOU SEE

873
00:26:50,093 --> 00:26:51,027
EXTREMELY HIGH MORTALITIES WHEN

874
00:26:51,027 --> 00:26:52,595
YOU'RE STARTING TO DEPLOY

875
00:26:52,595 --> 00:26:54,030
DEVICES, AND AGAIN, SMALL

876
00:26:54,030 --> 00:26:55,665
NUMBERS, NOT WELL SELECTED, BUT

877
00:26:55,665 --> 00:26:57,734
IT'S HARD TO ARGUE THAT YOU'RE

878
00:26:57,734 --> 00:26:58,835
MODIFYING OUT COME VERY MUCH

879
00:26:58,835 --> 00:27:00,570
WITH 60% MORTALITY OF SOMEBODY

880
00:27:00,570 --> 00:27:03,339
ON ECMO WHO'S ALREADY HIT

881
00:27:03,339 --> 00:27:04,641
CARDIOMETABOLIC SHOCK.

882
00:27:04,641 --> 00:27:06,276
SO WE OUGHT TO GET IN THERE

883
00:27:06,276 --> 00:27:07,577
EARLIER, WE HAVE TO FIGURE THIS

884
00:27:07,577 --> 00:27:09,446
OUT BEFORE THEY HIT THAT.

885
00:27:09,446 --> 00:27:11,848
LOOKING AT EVOLVING PREDICTORS,

886
00:27:11,848 --> 00:27:12,949
PREVIOUSLY PEOPLE LOOKED AT A

887
00:27:12,949 --> 00:27:15,118
LOT OF COMPLEX HEMODYNAMIC

888
00:27:15,118 --> 00:27:16,119
METRICS, SOME OF YOU MAY HAVE

889
00:27:16,119 --> 00:27:20,924
HEARD OF THINGS LIKE -- AS WE

890
00:27:20,924 --> 00:27:22,459
MOVE MORE GRANULAR AND WE LOOK

891
00:27:22,459 --> 00:27:25,962
IN LARGE COHORTS OF PATIENTS,

892
00:27:25,962 --> 00:27:26,629
ONE OF THE THINGS THAT STAND OUT

893
00:27:26,629 --> 00:27:27,497
IS DRIVING MORTALITY.

894
00:27:27,497 --> 00:27:29,232
AND THE THINGS THAT REALLY STAND

895
00:27:29,232 --> 00:27:32,535
OUT, LOW SVR, SYSTEMIC

896
00:27:32,535 --> 00:27:33,403
CONGESTION.

897
00:27:33,403 --> 00:27:34,804
AND THAT'S PHYSIOLOGY WE ALL

898
00:27:34,804 --> 00:27:35,138
LEARNED.

899
00:27:35,138 --> 00:27:37,107
YOU LOSE YOUR PERFUSION GRADIENT

900
00:27:37,107 --> 00:27:38,441
ACROSS YOUR ORGANS.

901
00:27:38,441 --> 00:27:43,012
AS YOUR MAP DROPS AND VENOUS

902
00:27:43,012 --> 00:27:44,347
OUTFLOW PRESSURE GETS HIGHER,

903
00:27:44,347 --> 00:27:45,982
YOU CAN'T DELIVER OX JEP TO YOUR

904
00:27:45,982 --> 00:27:46,516
ORGANS.

905
00:27:46,516 --> 00:27:48,051
THAT'S PHYSIOLOGY 101.

906
00:27:48,051 --> 00:27:50,253
THAT OVERWHELMINGLY OUTPOWERS OR

907
00:27:50,253 --> 00:27:51,454
PREDICTS MORTALITY THAN ALL

908
00:27:51,454 --> 00:27:52,756
THESE OTHER FANCY METRICS.

909
00:27:52,756 --> 00:27:54,624
SO WE'VE GOT TO GET AHEAD OF

910
00:27:54,624 --> 00:27:55,925
THAT, START IDENTIFYING PATIENTS

911
00:27:55,925 --> 00:27:56,993
BEFORE THEY'RE CONGESTED.

912
00:27:56,993 --> 00:27:58,828
IN ADDITION TO THAT, PATIENTS

913
00:27:58,828 --> 00:28:04,467
WHO ARE ON VASOP VASOPRESSORS, N

914
00:28:04,467 --> 00:28:06,002
ESCALATING, THAT IS A

915
00:28:06,002 --> 00:28:07,203
SIGNIFICANT PREDICTOR OF

916
00:28:07,203 --> 00:28:07,637
MORTALITY.

917
00:28:07,637 --> 00:28:09,272
PEOPLE ARE THINKING THIS IS

918
00:28:09,272 --> 00:28:11,341
SOMETHING WHO GOES FROM 1 TO 4.

919
00:28:11,341 --> 00:28:12,108
THAT'S NOT TRUE.

920
00:28:12,108 --> 00:28:16,613
YOU'RE LOOKING AT SWINGS AT .02

921
00:28:16,613 --> 00:28:17,046
TO .06.

922
00:28:17,046 --> 00:28:18,481
THAT TRIPLES YOUR MORTALITY.

923
00:28:18,481 --> 00:28:21,751
AND YOU CAN SEE, IT'S A

924
00:28:21,751 --> 00:28:22,619
PROGRESSIVE -- IT DEMONSTRATES

925
00:28:22,619 --> 00:28:23,820
HOW THAT'S A CONTINUUM.

926
00:28:23,820 --> 00:28:29,192
SO THESE CARDIOGENIC SHOCK --

927
00:28:29,192 --> 00:28:33,329
YOU'RE KIND OF WATCHING THEM,

928
00:28:33,329 --> 00:28:35,632
THAT CAN AFFECT THE CANARY IN

929
00:28:35,632 --> 00:28:36,065
THE COAL MINE.

930
00:28:36,065 --> 00:28:37,600
A LOT OF PEOPLE START LOOKING

931
00:28:37,600 --> 00:28:39,035
SAYING, WELL, LACTATE IS STILL

932
00:28:39,035 --> 00:28:39,469
FLAT.

933
00:28:39,469 --> 00:28:41,638
THIS IS A STUDY OF LOOKING AT

934
00:28:41,638 --> 00:28:43,072
ADVANCED HEART FAILURE PATIENTS

935
00:28:43,072 --> 00:28:46,509
AND LOOKING AT THEIR LACTATE

936
00:28:46,509 --> 00:28:46,810
PRODUCTION.

937
00:28:46,810 --> 00:28:48,444
FOCUS ON THE BOTTOM PANEL, THEY

938
00:28:48,444 --> 00:28:49,746
ESSENTIALLY SHOW THE SAME THING.

939
00:28:49,746 --> 00:28:52,048
IF YOU LOOK AT CARDIAC INDEX,

940
00:28:52,048 --> 00:28:54,450
THAT IS A LEVEL OF LACTATE

941
00:28:54,450 --> 00:28:55,552
PRODUCTION ASSOCIATED WITH EACH

942
00:28:55,552 --> 00:28:58,154
CARDIAC INDEX MEASURED BY RIGHT

943
00:28:58,154 --> 00:29:00,557
HEART CATH IN AN ADVANCED HEART

944
00:29:00,557 --> 00:29:01,291
FAILURE POPULATION.

945
00:29:01,291 --> 00:29:02,992
SO YOU SEE PEOPLE WITH INDICES

946
00:29:02,992 --> 00:29:05,161
IN THE 1s, VERY, VERY

947
00:29:05,161 --> 00:29:06,362
CRITICALLY LOW WHO ARE NOT

948
00:29:06,362 --> 00:29:06,796
MAKING LACTATE.

949
00:29:06,796 --> 00:29:08,665
IN MANY OF THE PATIENTS ACTUALLY

950
00:29:08,665 --> 00:29:10,733
MAKING LACTATE ARE ACTUALLY

951
00:29:10,733 --> 00:29:11,501
CIRCULATING NORMAL AMOUNTS OF

952
00:29:11,501 --> 00:29:12,035
BLOOD.

953
00:29:12,035 --> 00:29:13,803
YOU LOOK AT THEIR INNER MACK

954
00:29:13,803 --> 00:29:18,274
SCORING, IT GOES 1 TO 7 BUT 1ING

955
00:29:18,274 --> 00:29:19,275
TO 4 WHAT YOU SEE IN THE

956
00:29:19,275 --> 00:29:19,742
HOSPITAL.

957
00:29:19,742 --> 00:29:21,911
1 BEING THE SICKEST WE HAVE,

958
00:29:21,911 --> 00:29:24,547
ONLY ABOUT 40% OF THEM MAKE

959
00:29:24,547 --> 00:29:28,151
LACTATE ON PRESENTATION.

960
00:29:28,151 --> 00:29:29,252
SO YOU'RE THINKING THESE

961
00:29:29,252 --> 00:29:30,553
PATIENTS, THE EXPERT HAS ALL THE

962
00:29:30,553 --> 00:29:31,788
DATA IN FRONT OF THEM WALKING

963
00:29:31,788 --> 00:29:33,189
INTO THE ER, YOU DON'T HAVE ALL

964
00:29:33,189 --> 00:29:35,058
YOUR ECHO, YOUR SCAN, ALL THE

965
00:29:35,058 --> 00:29:36,459
PIECES OF THIS PERSON'S

966
00:29:36,459 --> 00:29:37,894
PHYSIOLOGY, THAT BASIC SCREEN OF

967
00:29:37,894 --> 00:29:38,761
CHECKING LACTATE, YOU'RE GOING

968
00:29:38,761 --> 00:29:42,732
TO MISS 60% OF YOUR INTERMAX

969
00:29:42,732 --> 00:29:43,466
1 PATIENTS DURING YOUR

970
00:29:43,466 --> 00:29:43,766
EVALUATION.

971
00:29:43,766 --> 00:29:45,201
SO THIS REALLY STARTS TO

972
00:29:45,201 --> 00:29:46,736
DESCRIBE WHY WE'RE MISSING THESE

973
00:29:46,736 --> 00:29:47,604
PATIENTS ON ADMISSION.

974
00:29:47,604 --> 00:29:49,038
IT BECOMES REALLY TRICKY.

975
00:29:49,038 --> 00:29:51,574
SO HOW DO WE IDENTIFY THESE

976
00:29:51,574 --> 00:29:52,008
PATIENTS?

977
00:29:52,008 --> 00:29:55,144
THERE ARE SOME NO MEL TOOLS,

978
00:29:55,144 --> 00:29:57,247
START GOOGLING BIOMARKERS AND

979
00:29:57,247 --> 00:29:58,014
CARDIOGENIC SHOCK.

980
00:29:58,014 --> 00:29:59,549
THERE'S SOME ROUTINE LABS THAT

981
00:29:59,549 --> 00:30:02,151
PEOPLE CAN SEND IF YOU SEE THAT

982
00:30:02,151 --> 00:30:04,454
BNP DOESN'T CLEAR DURING

983
00:30:04,454 --> 00:30:05,655
ADMISSION, THERE'S INCREASED

984
00:30:05,655 --> 00:30:07,957
MORTALITY BUT YOU'RE LOOKING AT

985
00:30:07,957 --> 00:30:09,292
TIMELINES OF 30 TO 60 DAYS.

986
00:30:09,292 --> 00:30:10,593
THIS DOESN'T HELP YOU IN THAT

987
00:30:10,593 --> 00:30:11,895
MINUTE TO MINUTE, DOESN'T HELP

988
00:30:11,895 --> 00:30:13,196
YOU UNDERSTAND, I HAVE SOMEBODY

989
00:30:13,196 --> 00:30:14,998
WHO'S UP IN FAR NORTHERN

990
00:30:14,998 --> 00:30:16,366
CALIFORNIA, HOW FAST DO I HAVE

991
00:30:16,366 --> 00:30:18,368
TO GET THEM TO US CF.

992
00:30:18,368 --> 00:30:19,869
BUT AGAIN, VALUABLE TOOL, AND IF

993
00:30:19,869 --> 00:30:21,404
YOU START SEEING THESE THINGS

994
00:30:21,404 --> 00:30:22,538
PERCOLATING, YOU CAN START

995
00:30:22,538 --> 00:30:24,607
PUTTING THEM INTO YOUR PRACTICE.

996
00:30:24,607 --> 00:30:25,708
ADDITIONALLY, THERE'S

997
00:30:25,708 --> 00:30:27,010
HIGH-THROUGHPUT PROAD YOE MIBG

998
00:30:27,010 --> 00:30:27,443
SCREENING.

999
00:30:27,443 --> 00:30:29,312
PEOPLE ARE USING -- THIS STUDY

1000
00:30:29,312 --> 00:30:31,948
WAS DONE SPECIFICALLY TO

1001
00:30:31,948 --> 00:30:34,684
DIFFERENTIATE CARDIOGENIC SHOCK

1002
00:30:34,684 --> 00:30:39,055
FROM HEART FA FAILURE.

1003
00:30:39,055 --> 00:30:40,857
AGAIN, THIS IS DIFFERENTIATING

1004
00:30:40,857 --> 00:30:41,691
PEOPLE WHO ARE IN SHOCK FROM

1005
00:30:41,691 --> 00:30:43,326
THOSE WHO AREN'T.

1006
00:30:43,326 --> 00:30:44,861
SO WHILE IT'S HELPFUL TO START

1007
00:30:44,861 --> 00:30:49,365
TO UNDERSTAND THE BIOLOGY,

1008
00:30:49,365 --> 00:30:50,900
YOU'RE TRYING TO PICK OUT THESE

1009
00:30:50,900 --> 00:30:52,435
PATIENTS BEFORE THEY MOVE INTO

1010
00:30:52,435 --> 00:30:53,403
METABOLIC ACIDOSIS, BEFORE THEY

1011
00:30:53,403 --> 00:30:57,774
GO INTO SHOCK.

1012
00:30:57,774 --> 00:30:58,675
SIMILARLY OTHERS SHOW A LOT OF

1013
00:30:58,675 --> 00:31:00,843
THE INTERLEUKINS, AND THIS IS

1014
00:31:00,843 --> 00:31:02,612
SHOWING IL-6, PARTICULARLY

1015
00:31:02,612 --> 00:31:05,882
ASSOCIATED WITH THE VASODILATORY

1016
00:31:05,882 --> 00:31:07,417
STATE, BUT AGAIN YOU'RE

1017
00:31:07,417 --> 00:31:08,084
IDENTIFYING LATE.

1018
00:31:08,084 --> 00:31:10,219
ONCE THIS HIGH RISK PHYSIOLOGY

1019
00:31:10,219 --> 00:31:14,424
HAS ALREADY SET IN.

1020
00:31:14,424 --> 00:31:17,360
DPP3, VERY INTERESTING MOLECULE,

1021
00:31:17,360 --> 00:31:18,695
ELABORATED FROM ENDOTHELIUM,

1022
00:31:18,695 --> 00:31:21,764
VERY, VERY HIGH FROM

1023
00:31:21,764 --> 00:31:23,599
NON-SURVIVORS, THIS IS ALSO PART

1024
00:31:23,599 --> 00:31:24,600
OF VASODILATORY SHOCK.

1025
00:31:24,600 --> 00:31:25,668
HOW YOU CAN START THINKING ABOUT

1026
00:31:25,668 --> 00:31:26,803
SOME OF THESE, THOSE ACTUALLY

1027
00:31:26,803 --> 00:31:28,304
MIGHT BE TREATMENT TARGETS.

1028
00:31:28,304 --> 00:31:31,374
YOU CAN USE AN ANTIBODY FOR

1029
00:31:31,374 --> 00:31:34,010
DP3 IN ANIMAL MODELS AND IMPROVE

1030
00:31:34,010 --> 00:31:34,577
BLOOD PRESSURE IN SHOCK.

1031
00:31:34,577 --> 00:31:35,979
SO STARTING TO THINK ABOUT

1032
00:31:35,979 --> 00:31:37,180
THESE, LIKE WE TALKED ABOUT

1033
00:31:37,180 --> 00:31:38,414
BEFORE, BEING MORE PRECISE,

1034
00:31:38,414 --> 00:31:39,816
THERE ARE OPPORTUNITIES TO

1035
00:31:39,816 --> 00:31:43,519
IDENTIFY TREATMENT TARGETS TO

1036
00:31:43,519 --> 00:31:45,355
HELP YOU TREAT HIGH RISK STAGES

1037
00:31:45,355 --> 00:31:46,489
BUT THE GOLD STANDARD IS ALWAYS

1038
00:31:46,489 --> 00:31:48,791
TO STAY OUT OF THAT, HOW DO YOU

1039
00:31:48,791 --> 00:31:49,959
STAY AHEAD OF IT.

1040
00:31:49,959 --> 00:31:51,394
SO WHAT IS NEEDED IN CARDIOGENIC

1041
00:31:51,394 --> 00:31:51,594
SHOCK?

1042
00:31:51,594 --> 00:31:53,830
YOU WANT TO IDENTIFY THESE

1043
00:31:53,830 --> 00:31:54,497
PATIENTS BEFORE THEY'RE THIS

1044
00:31:54,497 --> 00:31:54,831
SICK.

1045
00:31:54,831 --> 00:31:57,433
IF THEY HAVE TO GO ON TO

1046
00:31:57,433 --> 00:31:58,768
CARDIOPULMONARY BY PASS FOR

1047
00:31:58,768 --> 00:32:00,603
CARDIAC SURGERY, TRANSPLANT, YOU

1048
00:32:00,603 --> 00:32:02,171
CAN'T TRANSPLANT SOMEBODY IN

1049
00:32:02,171 --> 00:32:03,339
MULTISYSTEM ORGAN FAILURE,

1050
00:32:03,339 --> 00:32:04,440
THERE'S NOT GOING TO BE A

1051
00:32:04,440 --> 00:32:04,707
CANDIDATE.

1052
00:32:04,707 --> 00:32:06,075
HOW DO YOU FIGURE THESE PATIENTS

1053
00:32:06,075 --> 00:32:07,610
OUT, HOW DO YOU IDENTIFY THEM

1054
00:32:07,610 --> 00:32:08,511
FOR APPROPRIATE ESCALATION OF

1055
00:32:08,511 --> 00:32:10,480
CARE BEFORE IT'S TOO LATE?

1056
00:32:10,480 --> 00:32:12,448
AND THEN FOR PATIENTS AT HIGH

1057
00:32:12,448 --> 00:32:16,486
RISK OF CARDIOGENIC SHOCK, OR

1058
00:32:16,486 --> 00:32:21,324
ZOE, THATHAT'S A DUPLICATE, I A.

1059
00:32:21,324 --> 00:32:24,160
BUT THEME BEING, EARLIER

1060
00:32:24,160 --> 00:32:25,228
IDENTIFICATION, YOU WANT TO STAY

1061
00:32:25,228 --> 00:32:27,363
OUT OF SYSTEMIC ACIDOSIS, AND

1062
00:32:27,363 --> 00:32:29,632
HOW CAN BIOMARKERS HELP YOU

1063
00:32:29,632 --> 00:32:30,733
IDENTIFY THESE PATIENTS AHEAD OF

1064
00:32:30,733 --> 00:32:32,268
TIME?

1065
00:32:32,268 --> 00:32:40,309
WITH THAT --

1066
00:32:40,309 --> 00:32:41,010
>> THANK YOU VERY MUCH.

1067
00:32:41,010 --> 00:32:42,979
YOU CAN SEE WHY I GOT VERY

1068
00:32:42,979 --> 00:32:44,747
INTERESTED WHEN CONNOR PRESENTED

1069
00:32:44,747 --> 00:32:45,982
THESE.

1070
00:32:45,982 --> 00:32:50,553
IT'S A VERY COMPLEX AND

1071
00:32:50,553 --> 00:32:51,988
HETEROGENEOUS DISEASE.

1072
00:32:51,988 --> 00:32:54,724
INDEED, NHLBI ON THE HEART SIDE

1073
00:32:54,724 --> 00:32:55,925
AND THE NATIONAL ACADEMY OF

1074
00:32:55,925 --> 00:32:58,327
SCIENCE A FEW YEARS AGO PUT OUT

1075
00:32:58,327 --> 00:33:01,731
THESE STATEMENTS.

1076
00:33:01,731 --> 00:33:03,466
I SUMMARIZED THEM HERE AND THE

1077
00:33:03,466 --> 00:33:04,367
REFERENCES, WE'LL PROVIDE THEM

1078
00:33:04,367 --> 00:33:05,034
FOR PEOPLE WHO WOULD LIKE TO

1079
00:33:05,034 --> 00:33:05,668
READ.

1080
00:33:05,668 --> 00:33:06,235
IT'S A GOOD READ.

1081
00:33:06,235 --> 00:33:07,570
I WOULD RECOMMEND IT.

1082
00:33:07,570 --> 00:33:11,274
THERE'S A NEED FOR CLINICAL

1083
00:33:11,274 --> 00:33:14,343
EXPERTS TO DEFINE THESE CLINICAL

1084
00:33:14,343 --> 00:33:15,978
SYNDROMES IN A VERY ELABORATE

1085
00:33:15,978 --> 00:33:18,614
WAY.

1086
00:33:18,614 --> 00:33:20,149
HOWEVER, THERE IS A NEED FOR

1087
00:33:20,149 --> 00:33:23,219
DATA INTEGRATION, INTEGRATION OF

1088
00:33:23,219 --> 00:33:25,621
CLINICAL DATA, BIOMARKERS PLUS

1089
00:33:25,621 --> 00:33:30,093
MULTIPLE OMICS DATASETS TO

1090
00:33:30,093 --> 00:33:31,294
REDEFINE THIS HETEROGENEOUS

1091
00:33:31,294 --> 00:33:31,527
DISEASE.

1092
00:33:31,527 --> 00:33:33,496
THAT IS YOU'RE GOING FROM BIG

1093
00:33:33,496 --> 00:33:38,201
DATA TO PRECISION.

1094
00:33:38,201 --> 00:33:40,736
NHLBI TOOK ON EVEN A STEP

1095
00:33:40,736 --> 00:33:42,138
FARTHER WITH THESE BY CREATING

1096
00:33:42,138 --> 00:33:44,640
THESE ENTITY TRANS OMIC FOR

1097
00:33:44,640 --> 00:33:49,679
PRECISION MEDICINE OR TOP NET,

1098
00:33:49,679 --> 00:33:51,981
WHERE IN THEY PROVIDE

1099
00:33:51,981 --> 00:33:54,517
MULTI-MODALITY OMIC ASSESSMENT

1100
00:33:54,517 --> 00:33:56,719
WITH DATASETS THAT COULD BE

1101
00:33:56,719 --> 00:34:01,390
INTEGRATED NOW INTO CLINICAL MES

1102
00:34:01,390 --> 00:34:03,826
TO REDEFINE DISEASES LIKE WHAT

1103
00:34:03,826 --> 00:34:07,563
DR. O'BRIEN JUST TOLD US HERE.

1104
00:34:07,563 --> 00:34:09,332
THERE IS A NEED TO DEVELOP

1105
00:34:09,332 --> 00:34:10,233
BIOMARKERS THAT COULD BE

1106
00:34:10,233 --> 00:34:13,402
DEPLOYED EARLY TO IDENTIFY THESE

1107
00:34:13,402 --> 00:34:16,005
COMPLEX PATIENTS EARLY, TO GUIDE

1108
00:34:16,005 --> 00:34:17,440
THEM TOWARDS THE RIGHT KIND OF

1109
00:34:17,440 --> 00:34:22,278
TREATMENT.

1110
00:34:22,278 --> 00:34:25,348
CELL-FREE DNA.

1111
00:34:25,348 --> 00:34:26,782
THESE ARE SHORT FRAGMENTS OF DNA

1112
00:34:26,782 --> 00:34:29,218
THAT ARE RELEASED WHEN CELLS DIE

1113
00:34:29,218 --> 00:34:31,254
INTO THE CIRCULATION.

1114
00:34:31,254 --> 00:34:35,858
THEY ARE EARLY MARKERS OF INJURY

1115
00:34:35,858 --> 00:34:39,929
AND THEY'RE QUITE ABUNDANT IN

1116
00:34:39,929 --> 00:34:40,396
PLASMA.

1117
00:34:40,396 --> 00:34:42,131
I'LL GIVE YOU AN EXPERIENCE IN

1118
00:34:42,131 --> 00:34:42,732
TRANSPLANTATION AND HOPEFULLY

1119
00:34:42,732 --> 00:34:44,233
GIVE YOU A FEW CONCEPTS AND PASS

1120
00:34:44,233 --> 00:34:45,768
IT ON TO ASHLEY TO PROVIDE

1121
00:34:45,768 --> 00:34:46,502
EXPERIENCES IN CARDIOGENIC

1122
00:34:46,502 --> 00:34:50,673
SHOCK.

1123
00:34:50,673 --> 00:34:52,675
IF YOUR MARGIN TIMES ZERO AS THE

1124
00:34:52,675 --> 00:34:54,744
TIME A TRANSPLANT PATIENT GETS

1125
00:34:54,744 --> 00:34:56,479
REJECTION, THIS IS A HEART

1126
00:34:56,479 --> 00:34:57,480
TRANSPLANT GROUP OF PATIENTS.

1127
00:34:57,480 --> 00:35:00,016
THIS IS WHEN THEIR BIOPSY ON THE

1128
00:35:00,016 --> 00:35:01,751
PATIENT SHOWS ANY CLINICAL

1129
00:35:01,751 --> 00:35:03,953
SYMPTOMS.

1130
00:35:03,953 --> 00:35:05,254
CELL-FREE DNA FROM THAT

1131
00:35:05,254 --> 00:35:11,160
TRANSPLANTED ORGAN IS HIGH.

1132
00:35:11,160 --> 00:35:12,862
HOWEVER, 2 TO 4, 5, 6 MONTHS

1133
00:35:12,862 --> 00:35:15,865
BEFORE THAT BIOPSY BECOMES

1134
00:35:15,865 --> 00:35:16,766
POSITIVE, THERE'S ELEVATION IN

1135
00:35:16,766 --> 00:35:19,402
THE CELL-FREE DNA DERIVED FROM

1136
00:35:19,402 --> 00:35:21,571
THAT ORGAN.

1137
00:35:21,571 --> 00:35:23,105
EARLY, EARLY DETECTION.

1138
00:35:23,105 --> 00:35:24,874
BUT AGAIN, TRANSPLANT IS EASY

1139
00:35:24,874 --> 00:35:28,044
BECAUSE THERE'S GENOMIC

1140
00:35:28,044 --> 00:35:28,311
ADMIXTURE.

1141
00:35:28,311 --> 00:35:29,478
WHAT IF IN CARDIAC SHOCK OR

1142
00:35:29,478 --> 00:35:31,380
OTHER CONDITIONS WHERE THERE ARE

1143
00:35:31,380 --> 00:35:34,951
NO GENOMIC ADMIXTURE?

1144
00:35:34,951 --> 00:35:36,819
HERE'S REALLY WHERE I HIGHLIGHT

1145
00:35:36,819 --> 00:35:39,121
THE UNIQUE OPPORTUNITIES THAT

1146
00:35:39,121 --> 00:35:40,523
NIH PROVIDES US.

1147
00:35:40,523 --> 00:35:45,595
IT'S A SAND BOX, BUT THIS SAND

1148
00:35:45,595 --> 00:35:50,967
BOX IS WHERE YOU HAVE TRULY

1149
00:35:50,967 --> 00:35:55,338
DEDICATED BRILLIANT SCIENCES.

1150
00:35:55,338 --> 00:35:56,973
ALLOW ME TO TELL YOU THE NIH

1151
00:35:56,973 --> 00:35:59,075
HERE, BUT I'VE BEEN EXTREMELY

1152
00:35:59,075 --> 00:36:02,345
FORTUNATE TO FIND THESE PEOPLE

1153
00:36:02,345 --> 00:36:04,780
HERE.

1154
00:36:04,780 --> 00:36:08,050
THE CHIEF SCIENTIST IN OUR LAB,

1155
00:36:08,050 --> 00:36:09,252
DR. MOON JANG, DEVELOPED SOME

1156
00:36:09,252 --> 00:36:10,586
MODELS WHERE YOU COULD NOW LOOK

1157
00:36:10,586 --> 00:36:14,190
AT CELL-FREE DNA IN CONDITIONS

1158
00:36:14,190 --> 00:36:16,259
WITHOUT GENOMIC ADMIXTURE,

1159
00:36:16,259 --> 00:36:18,661
LEVERAGING TISSUE-SPECIFIC

1160
00:36:18,661 --> 00:36:20,229
EPIGENETIC MARKERS.

1161
00:36:20,229 --> 00:36:23,599
AND YOU CAN THEN USE THOSE

1162
00:36:23,599 --> 00:36:25,034
TISSUE EPIGENETIC MARKERS TO

1163
00:36:25,034 --> 00:36:27,803
SCAN CELL-FREE DNA COMING FROM

1164
00:36:27,803 --> 00:36:32,074
ALL THESE DIFFERENT ORGANS,

1165
00:36:32,074 --> 00:36:33,042
VASCULAR ENDOTHELIUM, HEART AND

1166
00:36:33,042 --> 00:36:36,679
ALL THESE ORGANS, PROVIDING A

1167
00:36:36,679 --> 00:36:39,749
WHOLE BODY MOLECULAR INJURY

1168
00:36:39,749 --> 00:36:40,182
SCAN.

1169
00:36:40,182 --> 00:36:42,051
WE'VE TESTED THAT IN MULTIPLE

1170
00:36:42,051 --> 00:36:45,988
DISEASES, AND IT SEEMS TO WORK.

1171
00:36:45,988 --> 00:36:48,624
I WAS GOING TO SHOW SOME SLIDE

1172
00:36:48,624 --> 00:36:52,361
HERE ON COVID-19 PATIENTS WHO

1173
00:36:52,361 --> 00:36:54,530
DIED -- SURVIVE, BUT I'LL LET

1174
00:36:54,530 --> 00:36:56,165
DR. PARK COME IN AND TRY TO GIVE

1175
00:36:56,165 --> 00:36:57,266
OUR EXPERIENCE IN CARDIOGENIC

1176
00:36:57,266 --> 00:36:57,833
SHOCK.

1177
00:36:57,833 --> 00:36:59,368
BUT WITH THESE METHODS, THESE

1178
00:36:59,368 --> 00:37:00,936
ARE THE DIFFERENT ORGANS THAT

1179
00:37:00,936 --> 00:37:05,741
YOU CAN QUANTIFY WITH 1 ML OF

1180
00:37:05,741 --> 00:37:06,842
PLASMA, YOU CAN QUANTIFY

1181
00:37:06,842 --> 00:37:08,044
THE DEGREE OF INJURY COMING FROM

1182
00:37:08,044 --> 00:37:10,012
ALL THESE DIFFERENT ORGANS.

1183
00:37:10,012 --> 00:37:11,113
THE LIBRARY CURRENTLY THAT WE

1184
00:37:11,113 --> 00:37:15,084
HAVE IN THE LAB CAN QUANTITATE

1185
00:37:15,084 --> 00:37:17,353
INJURY FROM AT MOST 35 DIFFERENT

1186
00:37:17,353 --> 00:37:18,120
TISSUE TYPES.

1187
00:37:18,120 --> 00:37:20,523
SO THE QUESTION THEN, HOW COULD

1188
00:37:20,523 --> 00:37:21,957
YOU USE THIS IN CARDIOGENIC

1189
00:37:21,957 --> 00:37:22,291
SHOCK?

1190
00:37:22,291 --> 00:37:23,826
I WOULD STOP HERE AND PASS IT

1191
00:37:23,826 --> 00:37:31,167
OVER TO DR. PARK.

1192
00:37:31,167 --> 00:37:32,535
>> HELLO.

1193
00:37:32,535 --> 00:37:36,639
THANK YOU, DR. AGBOR AND

1194
00:37:36,639 --> 00:37:37,106
DR. O'BRIEN FOR THIS

1195
00:37:37,106 --> 00:37:37,406
OPPORTUNITY.

1196
00:37:37,406 --> 00:37:38,507
ONE OF THE THINGS THAT WE'VE

1197
00:37:38,507 --> 00:37:40,242
HEARD OVER AND OVER AGAIN IS

1198
00:37:40,242 --> 00:37:41,344
THAT CARDIOGENIC SHOCK OUTCOMES

1199
00:37:41,344 --> 00:37:43,012
HAVE REALLY PLATEAUED OVER THE

1200
00:37:43,012 --> 00:37:46,082
LAST TWO DECADES, AND ONE NEED

1201
00:37:46,082 --> 00:37:47,817
IS TO IDENTIFY HIGH RISK

1202
00:37:47,817 --> 00:37:51,654
PATIENTS EARLIER ON.

1203
00:37:51,654 --> 00:37:52,321
AND ONE SPECIFIC AREA OF

1204
00:37:52,321 --> 00:37:54,156
INTEREST IS TO FIND BIOMARKERS

1205
00:37:54,156 --> 00:37:57,793
THAT ARE ABLE TO IDENTIFY THESE

1206
00:37:57,793 --> 00:37:58,794
PATIENTS.

1207
00:37:58,794 --> 00:37:59,795
SO ONE ATTRACTIVE CANDIDATE IS

1208
00:37:59,795 --> 00:38:01,630
THE USE OF CELL-FREE DNA IN

1209
00:38:01,630 --> 00:38:02,431
IDENTIFYING THESE PATIENTS.

1210
00:38:02,431 --> 00:38:03,733
SO BUILDING ON THIS, I'LL BE

1211
00:38:03,733 --> 00:38:05,034
PRESENTING SOME OF OUR EARLY

1212
00:38:05,034 --> 00:38:07,136
DATA THAT TAKES A LOOK AT

1213
00:38:07,136 --> 00:38:09,105
WHETHER ADMISSION CELL-FREE DNA

1214
00:38:09,105 --> 00:38:12,141
CAN HELP US IDENTIFY THESE HIGH

1215
00:38:12,141 --> 00:38:12,475
RISK PATIENTS.

1216
00:38:12,475 --> 00:38:13,376
SO IN ORDER TO ANSWER THIS

1217
00:38:13,376 --> 00:38:14,810
QUESTION, WE TOOK A LOOK AT A

1218
00:38:14,810 --> 00:38:17,446
COHORT TAKEN FROM THE UCSF

1219
00:38:17,446 --> 00:38:18,748
CARDIAC ICU.

1220
00:38:18,748 --> 00:38:20,416
SPECIFICALLY WE LOOKED AT THEIR

1221
00:38:20,416 --> 00:38:22,284
CARDIOGENIC SHOCK BIOBANK, WHICH

1222
00:38:22,284 --> 00:38:25,454
TAKES SAMPLES FROM PATIENTS ADD

1223
00:38:25,454 --> 00:38:27,556
ADMITTED TO THEIR CICU WITH A

1224
00:38:27,556 --> 00:38:28,657
DIAGNOSIS OF CARDIOGENIC SHOCK.

1225
00:38:28,657 --> 00:38:30,626
THIS WAS PART OF A LARGER

1226
00:38:30,626 --> 00:38:31,727
MULTI-INSTITUTIONAL EFFORT TO

1227
00:38:31,727 --> 00:38:32,828
FIND BIOMARKERS IN THIS

1228
00:38:32,828 --> 00:38:35,097
POPULATION.

1229
00:38:35,097 --> 00:38:37,199
NOW LOOKING SPECIFICALLY AT THE

1230
00:38:37,199 --> 00:38:40,069
UCSF BIOBANK ALONE, THIS BIOBANK

1231
00:38:40,069 --> 00:38:41,904
STARTED IN JANUARY OF 2023 AND

1232
00:38:41,904 --> 00:38:44,206
HAS MASSIVELY EXPANDED, AND TO

1233
00:38:44,206 --> 00:38:48,611
DATE HAS OVER 300 PATIENT

1234
00:38:48,611 --> 00:38:50,346
SAMPLES AND CLINICAL DATA THAT

1235
00:38:50,346 --> 00:38:52,415
WERE COLLECTED.

1236
00:38:52,415 --> 00:38:54,850
LOOKING A LITTLE BIT MORE

1237
00:38:54,850 --> 00:38:56,152
DETAIL, THIS BIOBANK COLLECTED

1238
00:38:56,152 --> 00:38:58,120
DATA AND SAMPLES FROM DAY ZERO,

1239
00:38:58,120 --> 00:39:01,323
DAY TWO AND DAY EIGHT AS OF

1240
00:39:01,323 --> 00:39:02,758
ADMISSION, AND ALONGSIDE THIS

1241
00:39:02,758 --> 00:39:04,059
CLINICAL DETAILS WERE COLLECTED,

1242
00:39:04,059 --> 00:39:06,495
SPANNING OVER 600 VARIABLES UP

1243
00:39:06,495 --> 00:39:09,231
UNTIL PATIENT DISCHARGE.

1244
00:39:09,231 --> 00:39:13,068
WE INITIALLY TOOK A LOOK AT THE

1245
00:39:13,068 --> 00:39:14,737
FIRST 225 PATIENTS OF WHICH THE

1246
00:39:14,737 --> 00:39:16,939
MEDIAN AGE WAS 58 YEARS, THE

1247
00:39:16,939 --> 00:39:18,574
MAJORITY OF PATIENTS HAD

1248
00:39:18,574 --> 00:39:20,843
INTERMEDIATE DISEASE SEVERITY

1249
00:39:20,843 --> 00:39:22,411
SCAI SHOCK C AND ABOUT 50% OF

1250
00:39:22,411 --> 00:39:24,079
PATIENTS HAD UNDERGONE CARDIAC

1251
00:39:24,079 --> 00:39:27,016
ARREST PRIOR TO ADMISSION.

1252
00:39:27,016 --> 00:39:28,451
OUR PRIMARY OUT COME OF INTEREST

1253
00:39:28,451 --> 00:39:30,219
WAS IN-HOSPITAL MORTALITY.

1254
00:39:30,219 --> 00:39:33,522
AND ACROSS THE 225 PATIENTS, WE

1255
00:39:33,522 --> 00:39:35,391
OBSERVED A 23% MORTALITY RATE

1256
00:39:35,391 --> 00:39:37,493
SHOWN HERE IN ORANGE.

1257
00:39:37,493 --> 00:39:39,128
AND SO WITH THIS AS OUR PRIMARY

1258
00:39:39,128 --> 00:39:41,730
OUT COME, WE REFRAMED OUR

1259
00:39:41,730 --> 00:39:43,632
QUESTION TO CAN ADMISSION

1260
00:39:43,632 --> 00:39:45,034
CELL-FREE DNA BE AN EARLY

1261
00:39:45,034 --> 00:39:46,469
INDICATOR OF MORTALITY IN THIS

1262
00:39:46,469 --> 00:39:46,802
POPULATION.

1263
00:39:46,802 --> 00:39:49,338
AND SO WHAT WE DID WAS WE TOOK

1264
00:39:49,338 --> 00:39:51,407
SAMPLES FROM DAY ZERO AND LOOKED

1265
00:39:51,407 --> 00:39:52,842
AT THEIR CELL-FREE DNA AND

1266
00:39:52,842 --> 00:39:55,911
CORRELATED THEM WITH OUR OUT OUE

1267
00:39:55,911 --> 00:39:57,780
OF IN-HOSPITAL MORTALITY.

1268
00:39:57,780 --> 00:39:59,315
WE FIRST ESTABLISH A BASELINE

1269
00:39:59,315 --> 00:40:01,183
UNDERSTANDING OF HOW HIGH

1270
00:40:01,183 --> 00:40:02,184
CELL-FREE DNA LEVELS WERE IN

1271
00:40:02,184 --> 00:40:04,153
THIS COHORT.

1272
00:40:04,153 --> 00:40:05,788
HERE WE COMPARE PATIENTS WITH

1273
00:40:05,788 --> 00:40:06,689
CARDIOGENIC SHOCK LABELED IN

1274
00:40:06,689 --> 00:40:08,357
RED, AND WE COMPARED THEM TO

1275
00:40:08,357 --> 00:40:10,860
HEALTHY INDIVIDUALS IN BLUE.

1276
00:40:10,860 --> 00:40:12,495
THEY'RE SEPARATED HERE ON THE X

1277
00:40:12,495 --> 00:40:15,498
AXIS BY THEIR SUBTYPE, SO

1278
00:40:15,498 --> 00:40:18,868
NUCLEAR OR MITOCHONDRIAL, AND WE

1279
00:40:18,868 --> 00:40:21,604
HAVE A SCALE OF LEVELS.

1280
00:40:21,604 --> 00:40:24,607
WHAT WAS STRIKING IS THAT

1281
00:40:24,607 --> 00:40:27,009
NUCLEAR AND MITOCHONDRIAL DNA

1282
00:40:27,009 --> 00:40:28,844
ARE 10 TIMES HIGHER IN

1283
00:40:28,844 --> 00:40:30,112
CARDIOGENIC SHOCK PATIENTS THAN

1284
00:40:30,112 --> 00:40:30,746
HEALTHY INDIVIDUALS.

1285
00:40:30,746 --> 00:40:33,315
WE THEN LOOKED AT HOW CELL-FREE

1286
00:40:33,315 --> 00:40:36,118
DNA LEVELS VARY BY CLINICAL

1287
00:40:36,118 --> 00:40:38,020
SEVERITY ON PRESENTATION, USING

1288
00:40:38,020 --> 00:40:39,321
THE SCAI SHOCK STAGING SYSTEM.

1289
00:40:39,321 --> 00:40:40,422
WHAT WE FOUND WAS THAT PATIENTS

1290
00:40:40,422 --> 00:40:42,191
WITH MORE SEVERE SHOCK ON

1291
00:40:42,191 --> 00:40:44,260
PRESENTATION HAD HIGHER

1292
00:40:44,260 --> 00:40:45,027
CELL-FREE DNA LEVELS.

1293
00:40:45,027 --> 00:40:47,229
SO THIS GAVE US A SNAPSHOT THAT

1294
00:40:47,229 --> 00:40:48,764
CELL-FREE DNA LEVELS CORRELATE

1295
00:40:48,764 --> 00:40:52,167
WITH HOW SICK SOMEONE IS ON

1296
00:40:52,167 --> 00:40:52,501
PRESENTATION.

1297
00:40:52,501 --> 00:40:56,138
BUT AS WE'VE SEEN CLINICALLY AND

1298
00:40:56,138 --> 00:40:57,673
AS WE'VE HEARD, SOMEONE'S

1299
00:40:57,673 --> 00:41:00,843
CLINICAL STATUS ISN'T

1300
00:41:00,843 --> 00:41:01,911
NECESSARILY STATIC, THAT MANY

1301
00:41:01,911 --> 00:41:03,379
PATIENTS WILL LATER ON GO ON TO

1302
00:41:03,379 --> 00:41:04,580
PROGRESS.

1303
00:41:04,580 --> 00:41:07,182
AND IN OUR COHORT, WE SAW THAT

1304
00:41:07,182 --> 00:41:09,818
35% OF PATIENTS EXPERIENCE

1305
00:41:09,818 --> 00:41:10,753
WORSENING IN DISEASE SEVERITY

1306
00:41:10,753 --> 00:41:12,354
DURING THEIR HOSPITAL STAY.

1307
00:41:12,354 --> 00:41:14,757
WE LABELED THESE PATIENTS AS

1308
00:41:14,757 --> 00:41:17,092
PROGRESSORS, SHOWN HERE IN

1309
00:41:17,092 --> 00:41:17,326
ORANGE.

1310
00:41:17,326 --> 00:41:18,360
SO THE NATURAL FOLLOW-UP

1311
00:41:18,360 --> 00:41:19,962
QUESTION WE HAD WAS, WELL, COULD

1312
00:41:19,962 --> 00:41:22,698
WE IDENTIFY EARLY ON WHO WOULD

1313
00:41:22,698 --> 00:41:25,568
GO ON TO PROGRESS LATER.

1314
00:41:25,568 --> 00:41:26,769
SPECIFICALLY WHERE THEIR

1315
00:41:26,769 --> 00:41:29,071
CELL-FREE DNA LEVELS ALREADY

1316
00:41:29,071 --> 00:41:31,807
ELEVATED AT TIME OF ADMISSION. 

1317
00:41:31,807 --> 00:41:33,509
WHAT WE FOUND WAS SUGGESTED THAT

1318
00:41:33,509 --> 00:41:34,944
THOSE WHO LATER WENT ON TO

1319
00:41:34,944 --> 00:41:36,679
PROGRESS ACTUALLY DID TEND TO

1320
00:41:36,679 --> 00:41:38,447
HAVE HIGHER LEVELS OF CELL-FREE

1321
00:41:38,447 --> 00:41:42,384
DNA ON ADMISSION.

1322
00:41:42,384 --> 00:41:43,919
THIS IS A VERY ALLURING CONCEPT

1323
00:41:43,919 --> 00:41:45,454
THAT CELL-FREE DNA, EVEN WHEN

1324
00:41:45,454 --> 00:41:48,123
TAKEN ON ADMISSION, MAY BE

1325
00:41:48,123 --> 00:41:49,525
DETECTING SOMETHING EVEN BEFORE

1326
00:41:49,525 --> 00:41:52,394
IT MANIFESTS AS OVERT CLINICAL

1327
00:41:52,394 --> 00:41:56,999
DECOMPENSATION.

1328
00:41:56,999 --> 00:41:58,100
SO, SO FAR WHAT WE'VE SEEN IS

1329
00:41:58,100 --> 00:41:59,635
THAT CELL-FREE DNA CORRELATES

1330
00:41:59,635 --> 00:42:01,170
WITH HOW SICK YOU ARE, WHETHER

1331
00:42:01,170 --> 00:42:03,606
YOU ARE LIKELY TO PROGRESS.

1332
00:42:03,606 --> 00:42:05,207
OUR NEXT QUESTION WAS CAN IT

1333
00:42:05,207 --> 00:42:06,775
TELL YOU HOW SICK YOU'RE GOING

1334
00:42:06,775 --> 00:42:08,243
TO BECOME, HOW SEVERE YOUR

1335
00:42:08,243 --> 00:42:09,545
DISEASE WILL GET.

1336
00:42:09,545 --> 00:42:13,482
THIS FIGURE SHOWS CELL-FREE DNA

1337
00:42:13,482 --> 00:42:15,217
PLOTTED AGAINST SOMEONE'S WORST

1338
00:42:15,217 --> 00:42:16,685
OR PEAK SCAI SHOCK STAGE AND

1339
00:42:16,685 --> 00:42:18,754
AGAIN, WE FOUND A STRONG GRADED

1340
00:42:18,754 --> 00:42:19,622
RELATIONSHIP IN THAT PATIENTS

1341
00:42:19,622 --> 00:42:21,924
WHO WENT ON TO DEVELOP MORE

1342
00:42:21,924 --> 00:42:22,992
SEVERE STAGES DURING THEIR

1343
00:42:22,992 --> 00:42:24,693
HOSPITAL STAY HAD HIGHER

1344
00:42:24,693 --> 00:42:26,228
CELL-FREE DNA LEVELS AT

1345
00:42:26,228 --> 00:42:27,896
ADMISSION, SO AGAIN THIS, IS

1346
00:42:27,896 --> 00:42:29,965
REINFORCING THAT SAME CONCEPT

1347
00:42:29,965 --> 00:42:32,034
THAT CELL-FREE DNA CAN BE AN

1348
00:42:32,034 --> 00:42:33,135
EARLY RISK STRATIFICATION TOOL

1349
00:42:33,135 --> 00:42:34,603
AND HELP US TO ANTICIPATE

1350
00:42:34,603 --> 00:42:35,571
CLINICAL TRAJECTORIES EVEN

1351
00:42:35,571 --> 00:42:37,006
BEFORE IT'S APPARENT.

1352
00:42:37,006 --> 00:42:38,207
SO NOW WHAT DOES THIS MEAN IN

1353
00:42:38,207 --> 00:42:40,009
TERMS OF MORTALITY?

1354
00:42:40,009 --> 00:42:41,877
WHEN WE LOOK AT THE GROUP AS A

1355
00:42:41,877 --> 00:42:44,046
WHOLE, WE SEE THAT PATIENTS WHO

1356
00:42:44,046 --> 00:42:45,814
WENT ON TO DIE DURING THEIR

1357
00:42:45,814 --> 00:42:47,049
HOSPITAL STAY HAD HIGHER

1358
00:42:47,049 --> 00:42:48,117
CELL-FREE DNA LEVELS ON

1359
00:42:48,117 --> 00:42:49,451
ADMISSION.

1360
00:42:49,451 --> 00:42:53,155
WE THEN STRATIFIED THEM BY THEIR

1361
00:42:53,155 --> 00:42:55,257
INITIAL SCAI SHOCK STAGE OR

1362
00:42:55,257 --> 00:42:56,158
THEIR CLINICAL SCORE AND

1363
00:42:56,158 --> 00:42:58,093
COMPARED CELL-FREE DNA LEVELS BY

1364
00:42:58,093 --> 00:42:59,762
THEIR OUTCOME WHETHER THEY

1365
00:42:59,762 --> 00:43:02,765
SURVIVED OR N NOT.

1366
00:43:02,765 --> 00:43:04,400
WHAT'S STRIKING IS PATIENTS WHO

1367
00:43:04,400 --> 00:43:06,568
DIE TENDED TO HAVE HIGHER

1368
00:43:06,568 --> 00:43:07,603
CELL-FREE DNA LEVELS AT

1369
00:43:07,603 --> 00:43:08,170
ADMISSION.

1370
00:43:08,170 --> 00:43:10,673
SO THIS REINFORCES THAT IDEA

1371
00:43:10,673 --> 00:43:12,207
THAT CELL-FREE DNA MAY BE

1372
00:43:12,207 --> 00:43:13,942
PROVIDING ADDITIONAL INFORMATION

1373
00:43:13,942 --> 00:43:15,744
THAT'S NOT PRESENT WITH JUST THE

1374
00:43:15,744 --> 00:43:17,246
CLINICAL SCORE ALONE, AND THAT

1375
00:43:17,246 --> 00:43:20,749
PERHAPS THIS MAY BE ESPECIALLY

1376
00:43:20,749 --> 00:43:22,051
BENEFICIAL IN IDENTIFYING WHICH

1377
00:43:22,051 --> 00:43:23,852
PATIENTS MAY BE THE ONES TO

1378
00:43:23,852 --> 00:43:27,256
INTERVENE EARLIER ON AND

1379
00:43:27,256 --> 00:43:29,224
THEREFORE MAY BE THE BEST

1380
00:43:29,224 --> 00:43:30,225
CANDIDATES FOR ADVANCED

1381
00:43:30,225 --> 00:43:31,026
THERAPIES.

1382
00:43:31,026 --> 00:43:33,328
WE THEN LOOKED AT HOW WELL

1383
00:43:33,328 --> 00:43:34,997
CELL-FREE DNA PERFORMED AGAINST

1384
00:43:34,997 --> 00:43:36,732
THESE OTHER CLINICAL SCORES, AND

1385
00:43:36,732 --> 00:43:39,501
WE STARTED BY EVALUATING SOME

1386
00:43:39,501 --> 00:43:46,375
TRADITIONAL SCORES LIKE SCAI,

1387
00:43:46,375 --> 00:43:48,177
SOFA -- IN ICU PATIENTS.

1388
00:43:48,177 --> 00:43:49,378
INDIVIDUALLY, THEY PERFORMED

1389
00:43:49,378 --> 00:43:50,713
POORLY IN TREE PREE

1390
00:43:50,713 --> 00:43:52,114
DICTIONARYING INHOSPITAL

1391
00:43:52,114 --> 00:43:54,149
MORTALITY WITH AUCs RANGING

1392
00:43:54,149 --> 00:43:55,451
FROM .53 TO .63.

1393
00:43:55,451 --> 00:43:57,186
WHEN WE LOOKED AT NUCLEAR

1394
00:43:57,186 --> 00:43:59,555
CELL-FREE DNA ALONE, WE SAW THAT

1395
00:43:59,555 --> 00:44:01,623
THERE WAS A MARKED IMPROVEMENT

1396
00:44:01,623 --> 00:44:04,993
WITH THE AUC OF 7.765.

1397
00:44:04,993 --> 00:44:07,262
AND WHEN WE COMBINE CELL-FREE

1398
00:44:07,262 --> 00:44:09,098
DNA WITH A CLINICAL SCORE LIKE

1399
00:44:09,098 --> 00:44:11,834
SCAI, THE AUC IMPROVED FURTHER

1400
00:44:11,834 --> 00:44:12,434
TO .784.

1401
00:44:12,434 --> 00:44:13,802
WHILE THE DIFFERENCE BETWEEN

1402
00:44:13,802 --> 00:44:15,204
THIS COMBINED SCORE AND

1403
00:44:15,204 --> 00:44:16,972
CELL-FREE DNA ALONE IS MARGINAL,

1404
00:44:16,972 --> 00:44:18,707
WHEN YOU COMPARE TO THE

1405
00:44:18,707 --> 00:44:21,376
INDIVIDUAL CLINICAL SCORES, IT

1406
00:44:21,376 --> 00:44:23,445
PERFORMS SUBSTANTIALLY BETTER.

1407
00:44:23,445 --> 00:44:27,816
SO JUST TO SUMMARIZE, WE HAVE

1408
00:44:27,816 --> 00:44:31,019
SEEN THAT CELL-FREE DNA IS

1409
00:44:31,019 --> 00:44:31,887
SUBSTANTIALLY HIGHER IN THIS

1410
00:44:31,887 --> 00:44:32,988
POPULATION, THAT THE DEGREE OF

1411
00:44:32,988 --> 00:44:34,123
ELEVATION TRACKS WITH HOW SICK A

1412
00:44:34,123 --> 00:44:35,524
PATIENT IS AND HOW SICK THEY ARE

1413
00:44:35,524 --> 00:44:38,927
LIKELY TO BECOME.

1414
00:44:38,927 --> 00:44:40,796
AND IMPORTANTLY IT PERFORMS

1415
00:44:40,796 --> 00:44:41,697
BETTER THAN THESE CLINICAL

1416
00:44:41,697 --> 00:44:44,767
SCORES THAT WE'RE USING ALONE.

1417
00:44:44,767 --> 00:44:46,301
SO WHILE OUR CURRENT WORK HAS

1418
00:44:46,301 --> 00:44:47,536
FOCUSED A LOT ON TOTAL AMOUNTS

1419
00:44:47,536 --> 00:44:49,605
OF CELL-FREE DNA AS A MARKER OF

1420
00:44:49,605 --> 00:44:53,308
SEVERITY AND MORTALITY, OUR NEXT

1421
00:44:53,308 --> 00:44:54,543
QUESTION WAS TO ASK WHERE THE

1422
00:44:54,543 --> 00:44:55,544
CELL-FREE DNA IS COMING FROM AND

1423
00:44:55,544 --> 00:44:57,179
WHAT CAN IT TELL US ABOUT END

1424
00:44:57,179 --> 00:44:58,647
ORGAN INJURY.

1425
00:44:58,647 --> 00:45:01,216
AND SO DR. AGBOR HAD INTRODUCED

1426
00:45:01,216 --> 00:45:02,785
THIS IDEA OF METHYLATION, AND

1427
00:45:02,785 --> 00:45:04,219
WHILE WE HAVEN'T DONE

1428
00:45:04,219 --> 00:45:06,555
METHYLATION ANALYSIS ON OUR

1429
00:45:06,555 --> 00:45:07,856
CARDIOGENIC SHOCK PATIENTS, IN A

1430
00:45:07,856 --> 00:45:09,258
SEPARATE COHORT OF END STAGE

1431
00:45:09,258 --> 00:45:10,826
HEART FAILURE PATIENTS, WE'VE

1432
00:45:10,826 --> 00:45:12,161
SHOWN THAT CELL-FREE DNA CAN BE

1433
00:45:12,161 --> 00:45:14,363
TRACED BACK TO SPECIFIC TISSUES

1434
00:45:14,363 --> 00:45:16,331
AND THIS CAN -- AND THE TISSUE

1435
00:45:16,331 --> 00:45:18,200
INJURY PATTERNS CAN BE DYNAMIC

1436
00:45:18,200 --> 00:45:20,402
IN RESPONSE TO THERAPY.

1437
00:45:20,402 --> 00:45:22,371
HERE WE HAVE A HEAT MAP THAT

1438
00:45:22,371 --> 00:45:24,173
ILLUSTRATES HOW CELL-FREE DNA

1439
00:45:24,173 --> 00:45:25,474
SIGNATURES CHANGE OR EVOLVE

1440
00:45:25,474 --> 00:45:27,342
ACROSS ORGAN SYSTEMS AND IMMUNE

1441
00:45:27,342 --> 00:45:28,911
SYSTEMS, AND THIS REFLECTS

1442
00:45:28,911 --> 00:45:30,879
DYNAMIC SHIFTS IN RESPONSE TO

1443
00:45:30,879 --> 00:45:32,214
LVAD.

1444
00:45:32,214 --> 00:45:33,515
AND OUR GOAL NOW IS TO BRING

1445
00:45:33,515 --> 00:45:35,517
THIS LENS TO CARDIOGENIC SHOCK

1446
00:45:35,517 --> 00:45:37,386
TO SEE IF WE CAN USE CELL-FREE

1447
00:45:37,386 --> 00:45:39,688
DNA TO TRACK REALTIME CHANGES

1448
00:45:39,688 --> 00:45:41,790
AND MONITOR END ORGAN INJURY IN

1449
00:45:41,790 --> 00:45:45,527
THIS POPULATION.

1450
00:45:45,527 --> 00:45:47,830
SO FINALLY TO BRING US HOME,

1451
00:45:47,830 --> 00:45:49,565
TODAY WE PAINTED THE LAND SKIP

1452
00:45:49,565 --> 00:45:50,732
OF CARDIOGENIC SHOCK.

1453
00:45:50,732 --> 00:45:51,834
WE CURRENTLY USE A COMBINATION

1454
00:45:51,834 --> 00:45:54,670
OF CLINICAL ASSESSMENT TOOLS AND

1455
00:45:54,670 --> 00:45:55,938
BIOMARKERS THAT WE'VE SEEN OVER

1456
00:45:55,938 --> 00:45:57,573
AND OVER AGAIN THAT THESE TOOLS

1457
00:45:57,573 --> 00:45:59,107
ARE LIMITED.

1458
00:45:59,107 --> 00:46:01,276
SPECIFICALLY WHEN WE LOOK AT

1459
00:46:01,276 --> 00:46:02,644
BIOMARKERS, THE BIOMARKERS THAT

1460
00:46:02,644 --> 00:46:03,946
ARE CURRENTLY AVAILABLE OFTEN

1461
00:46:03,946 --> 00:46:05,380
REFLECT TISSUE DAMAGE THAT HAS

1462
00:46:05,380 --> 00:46:07,382
ALREADY OCCURRED AND IT'S

1463
00:46:07,382 --> 00:46:09,017
IRREVERSIBLE, AND OFTEN COMES

1464
00:46:09,017 --> 00:46:12,955
AFTER CLINICAL DECOMPENSATION.

1465
00:46:12,955 --> 00:46:14,056
IN CONTRAST, OUR PRELIMINARY

1466
00:46:14,056 --> 00:46:16,391
WORK FEATURES CELL-FREE DNA AS A

1467
00:46:16,391 --> 00:46:18,126
BIOMARKER THAT CAN PRECEDE

1468
00:46:18,126 --> 00:46:19,761
CLINICAL DEEXRENNIZATION AND MAY

1469
00:46:19,761 --> 00:46:21,363
BE AN EARLIER PREDICTOR OF

1470
00:46:21,363 --> 00:46:24,900
FURTHER PROGRESSION AND DEATH.

1471
00:46:24,900 --> 00:46:27,669
SO ACTUALLY WHAT WE HYPOTHESIZED

1472
00:46:27,669 --> 00:46:28,837
MOVING FORWARD IS THAT CELL-FREE

1473
00:46:28,837 --> 00:46:31,840
DNA MAY AUGMENT THESE EXISTING

1474
00:46:31,840 --> 00:46:33,275
SCORES, ESPECIALLY AS WE

1475
00:46:33,275 --> 00:46:34,509
UNDERSTAND MORE ABOUT END ORGAN

1476
00:46:34,509 --> 00:46:35,711
INJURY AND HOW THAT CHANGES

1477
00:46:35,711 --> 00:46:37,846
DURING THEIR HOSPITAL STAY.

1478
00:46:37,846 --> 00:46:39,314
THIS WILL ULTIMATELY HELP US TO

1479
00:46:39,314 --> 00:46:40,782
IDENTIFY THOSE WHO ARE AT

1480
00:46:40,782 --> 00:46:42,117
HIGHEST RISK AND, THEREFORE, MAY

1481
00:46:42,117 --> 00:46:48,724
BE THE BEST CANDIDATES FOR MPS.

1482
00:46:48,724 --> 00:46:48,924
BS.

1483
00:46:48,924 --> 00:46:49,691
THANK YOU FOR YOUR ATTENTION.

1484
00:46:49,691 --> 00:46:51,226
I WOULD BE REMISS WITHOUT

1485
00:46:51,226 --> 00:46:52,995
MENTIONING OUR MASSIVE, MASSIVE

1486
00:46:52,995 --> 00:46:56,198
TEAM ACROSS BOTH THE NIH AND

1487
00:46:56,198 --> 00:46:56,632
UCSF.

1488
00:46:56,632 --> 00:46:59,268
THIS IS OUR NIH TEAM, WHICH I

1489
00:46:59,268 --> 00:47:04,773
HAVE TO JUST MENTION A FEW

1490
00:47:04,773 --> 00:47:07,409
PEOPLE WHO HAVE BEEN SUPER

1491
00:47:07,409 --> 00:47:08,944
INSTRUMENTAL IN MOVING THE

1492
00:47:08,944 --> 00:47:10,579
SCIENCE FORWARD AND OF COURSE

1493
00:47:10,579 --> 00:47:11,613
DR. MOON JANG FOR DEVELOPING A

1494
00:47:11,613 --> 00:47:14,349
LOT OF THESE TECHNOLOGIES.

1495
00:47:14,349 --> 00:47:16,985
AND THEN HERE IS THE UCSF TEAM,

1496
00:47:16,985 --> 00:47:18,553
ALSO ANOTHER MASSIVE TEAM THAT

1497
00:47:18,553 --> 00:47:20,422
HAVE BEEN REALLY WORKHORSES IN

1498
00:47:20,422 --> 00:47:21,623
GETTING ALL OF THIS DATA TO US

1499
00:47:21,623 --> 00:47:22,991
AND ALL THE SAMPLES PROCESSED

1500
00:47:22,991 --> 00:47:24,726
FOR US.

1501
00:47:24,726 --> 00:47:25,928
SO WITH THAT, WE'LL TAKE

1502
00:47:25,928 --> 00:47:27,362
QUESTIONS AND THANK YOU FOR YOUR

1503
00:47:27,362 --> 00:47:28,030
TIME.

1504
00:47:28,030 --> 00:47:38,206
[APPLAUSE]

1505
00:47:40,609 --> 00:47:41,643
>> PLEASE COME UP TO THE

1506
00:47:41,643 --> 00:47:41,977
MICROPHONE.

1507
00:47:41,977 --> 00:47:45,447
FOR THOSE ONLINE, SEND YOUR

1508
00:47:45,447 --> 00:47:46,114
EMAIL.

1509
00:47:46,114 --> 00:47:55,457
WE'RE VERY FORTUNATE DR. MAZUR

1510
00:47:55,457 --> 00:47:56,525
WILL CHECK THE QUESTIONS.

1511
00:47:56,525 --> 00:47:58,427
>> I'LL KICK OFF THE
QUESTIONS

1512
00:47:58,427 --> 00:48:00,529
BECAUSE THERE DOESN'T SEEM TO BE

1513
00:48:00,529 --> 00:48:01,530
SOMEBODY DUELING AT THE OTHER

1514
00:48:01,530 --> 00:48:02,197
MICROPHONE.

1515
00:48:02,197 --> 00:48:03,198
REALLY NICE COMPOSITE

1516
00:48:03,198 --> 00:48:04,399
PRESENTATION AMONG ALL OF YOU.

1517
00:48:04,399 --> 00:48:05,534
REALLY ENJOYED IT.

1518
00:48:05,534 --> 00:48:06,635
ONE THING THAT COMES TO MIND

1519
00:48:06,635 --> 00:48:07,836
KIND OF RIGHT AT THE END IS, HOW

1520
00:48:07,836 --> 00:48:10,672
DO YOU IMPLEMENT OR TEST TO

1521
00:48:10,672 --> 00:48:12,674
VALIDATE THAT THE ADDITION OF

1522
00:48:12,674 --> 00:48:14,443
CELL-FREE DNA WILL HELP TRIAGE

1523
00:48:14,443 --> 00:48:17,813
AND ULTIMATELY HELP IMPROVE

1524
00:48:17,813 --> 00:48:19,514
OUTCOMES FROM CARDIOGENIC SHOCK?

1525
00:48:19,514 --> 00:48:22,351
SO CAN YOU DO A PRE/POST, IS

1526
00:48:22,351 --> 00:48:25,420
THERE A POINT OF CARE THAT YOU

1527
00:48:25,420 --> 00:48:26,588
CAN, YOU KNOW, IMPLEMENT TO BE

1528
00:48:26,588 --> 00:48:28,023
ABLE TO GIVE YOU THE TRIAGE

1529
00:48:28,023 --> 00:48:30,092
INFORMATION THAT YOU WOULD THEN

1530
00:48:30,092 --> 00:48:31,259
PROPOSE A DIFFERENT TRIAGE

1531
00:48:31,259 --> 00:48:32,494
SYSTEM AND COMPARE MORTALITY

1532
00:48:32,494 --> 00:48:34,930
BEFORE THE IMPLEMENTATION VERSUS

1533
00:48:34,930 --> 00:48:36,365
AFTER, BUT WHAT'S THE NEXT STEP?

1534
00:48:36,365 --> 00:48:38,333
HOW DO YOU KIND OF ASSESS

1535
00:48:38,333 --> 00:48:40,435
WHETHER THIS IS A MEANINGFULLY

1536
00:48:40,435 --> 00:48:42,104
ADDITIONAL USEFUL TOOL AT THE

1537
00:48:42,104 --> 00:48:43,071
BEDSIDE AT THE TIME OF

1538
00:48:43,071 --> 00:48:45,841
ADMISSION?

1539
00:48:45,841 --> 00:48:47,376
>> SO I COULD GIVE YOU A
SENSE

1540
00:48:47,376 --> 00:48:49,811
OF THE TECHNOLOGY AND THEN

1541
00:48:49,811 --> 00:48:52,547
DR. O'BRIEN IS AN EXPERT IN THE

1542
00:48:52,547 --> 00:48:55,851
SYSTEMS, COULD HELP DO THAT.

1543
00:48:55,851 --> 00:48:58,720
SO THE TECHNOLOGIES ARE GETTING

1544
00:48:58,720 --> 00:49:00,355
WAY SMALLER.

1545
00:49:00,355 --> 00:49:02,524
WHEN I CAME HERE FOR FELLOWSHIP

1546
00:49:02,524 --> 00:49:05,160
AT THE NIH, THE SEQUENCING

1547
00:49:05,160 --> 00:49:08,697
MACHINE WAS ABOUT THIS BIG.

1548
00:49:08,697 --> 00:49:12,534
NOW WE HAVE SYSTEMS ABOUT THE

1549
00:49:12,534 --> 00:49:13,869
SIZE OF A FLASH DRIVE THAT YOU

1550
00:49:13,869 --> 00:49:15,337
CAN TAKE INTO THE FIELD, AND

1551
00:49:15,337 --> 00:49:17,305
THEN THEY'VE BEEN DIGITAL

1552
00:49:17,305 --> 00:49:19,574
DROPLET PCR SYSTEMS THAT HAVE

1553
00:49:19,574 --> 00:49:22,277
BEEN DEVELOPED WHICH CAN GIVE

1554
00:49:22,277 --> 00:49:23,812
YOU ASSAY TURNAROUND TIME WITHIN

1555
00:49:23,812 --> 00:49:24,346
HOURS.

1556
00:49:24,346 --> 00:49:25,680
THEN ON THE BLOOD COLLECTION

1557
00:49:25,680 --> 00:49:26,648
SIDE, THERE HAVE BEEN PAPER

1558
00:49:26,648 --> 00:49:27,783
STRIPS THAT HAVE NOW BEEN

1559
00:49:27,783 --> 00:49:30,419
DEVELOPED WHERE WITH THE PRICK

1560
00:49:30,419 --> 00:49:32,621
OF A FINGER, JUST LIKE A

1561
00:49:32,621 --> 00:49:33,855
GLUCOMETER, AND YOU DROP A FEW

1562
00:49:33,855 --> 00:49:36,725
OUNCES OF -- DROPS OF BLOOD ON

1563
00:49:36,725 --> 00:49:39,094
THE PAPER, IT CAN SEPARATE OUT

1564
00:49:39,094 --> 00:49:43,231
CELLS FROM PLASMA, GIVING YOU AN

1565
00:49:43,231 --> 00:49:44,533
OPPORTUNITY TO THEN ASSESS JUST

1566
00:49:44,533 --> 00:49:44,866
PLASMA.

1567
00:49:44,866 --> 00:49:46,768
SO I THINK THAT THE TECHNOLOGIES

1568
00:49:46,768 --> 00:49:47,202
ARE HERE NOW.

1569
00:49:47,202 --> 00:49:51,473
AND YOU KNOW, THE NIH DIRECTOR

1570
00:49:51,473 --> 00:49:52,674
HAS THIS GRANT WHICH IS CALLED

1571
00:49:52,674 --> 00:49:55,677
THE NIH DIRECTOR'S GRANT, WHICH

1572
00:49:55,677 --> 00:49:59,748
ALLOWS FOR HIGH RISK, BUT HIGH

1573
00:49:59,748 --> 00:50:01,750
IMPACT, WHERE YOU CAN

1574
00:50:01,750 --> 00:50:07,322
MINIATURIZE THESE DEVICES, AND

1575
00:50:07,322 --> 00:50:09,391
COLLEAGUES IN THE INSTITUTE OF

1576
00:50:09,391 --> 00:50:10,392
LABORATORY MEDICINE ARE

1577
00:50:10,392 --> 00:50:11,626
BEGINNING TO THINK ABOUT THOSE

1578
00:50:11,626 --> 00:50:11,927
APPROACHES.

1579
00:50:11,927 --> 00:50:13,095
SO THE TECHNOLOGIES ARE THERE

1580
00:50:13,095 --> 00:50:14,062
AND CAN BE DEVELOPED.

1581
00:50:14,062 --> 00:50:16,698
NOW HOW THEY WOULD IMPROVE

1582
00:50:16,698 --> 00:50:19,701
OUTCOMES, I THINK DR. O'BRIEN

1583
00:50:19,701 --> 00:50:22,571
CAN -- AND ASHLEY COULD GIVE

1584
00:50:22,571 --> 00:50:23,305
SENSE INTO THAT.

1585
00:50:23,305 --> 00:50:25,307
I WILL STEP BACK.

1586
00:50:25,307 --> 00:50:27,509
>> SO IT'S A VERY
COMPLICATED

1587
00:50:27,509 --> 00:50:29,077
QUESTION AND I THINK ONE OF THE

1588
00:50:29,077 --> 00:50:30,378
THINGS THAT WOULD BE WHERE THE

1589
00:50:30,378 --> 00:50:32,247
USE CASE DIFFERS FROM THE PLACE

1590
00:50:32,247 --> 00:50:34,282
WHERE YOU HAVE YOUR PROOF OF

1591
00:50:34,282 --> 00:50:35,150
CONCEPT IS IMPORTANT HERE.

1592
00:50:35,150 --> 00:50:37,319
SO YOU GO TO A TERTIARY MEDICAL

1593
00:50:37,319 --> 00:50:38,920
CENTER AND YOUR ABILITY TO TEASE

1594
00:50:38,920 --> 00:50:40,989
OUT ALL THE SAFETY LAYERS THAT

1595
00:50:40,989 --> 00:50:42,424
COULD INTERVENE ON A PATIENT TO

1596
00:50:42,424 --> 00:50:43,825
GET THEM TO THE SAME PLACE IS

1597
00:50:43,825 --> 00:50:45,427
VERY, VERY DIFFICULT.

1598
00:50:45,427 --> 00:50:46,962
NOBODY IS GOING TO LET A PATIENT

1599
00:50:46,962 --> 00:50:48,830
JUST DRIFT.

1600
00:50:48,830 --> 00:50:50,932
AND THERE'S A LOT OF WAYS,

1601
00:50:50,932 --> 00:50:51,933
ESPECIALLY WHEN YOU HAVE PEOPLE

1602
00:50:51,933 --> 00:50:53,668
WORK IN AN ICU AND HAVE HEART

1603
00:50:53,668 --> 00:50:55,203
FAIL DOCTORS AROUND, THE DEEDS

1604
00:50:55,203 --> 00:50:56,138
RECOGNITION IS GOING TO BE EARLY

1605
00:50:56,138 --> 00:50:57,439
SO PEOPLE ARE GOING TO SEE LOW

1606
00:50:57,439 --> 00:50:58,874
PULSE PRESSURE AND CALL THE ICU

1607
00:50:58,874 --> 00:51:02,511
OR GET AN  AN ECHO AND LOOK AT E

1608
00:51:02,511 --> 00:51:03,178
NUANCES OF THE ECHO.

1609
00:51:03,178 --> 00:51:05,046
SO I WOULD IMAGINE WHERE YOU'D

1610
00:51:05,046 --> 00:51:05,981
WANT TO PROVE THIS AFTER YOU

1611
00:51:05,981 --> 00:51:07,482
HAVE SOME SENSE OF WHAT DO THE

1612
00:51:07,482 --> 00:51:09,151
RELATIVE OUTCOMES ACROSS THESE

1613
00:51:09,151 --> 00:51:11,887
GROUPS AND IMPORTANTLY I THINK

1614
00:51:11,887 --> 00:51:13,588
WE HAVE TO GET TRAJECTORY OF

1615
00:51:13,588 --> 00:51:15,657
CHANGE ON CELL-FREE DNA, BECAUSE

1616
00:51:15,657 --> 00:51:17,125
USING IT AS A POINT OF CARE

1617
00:51:17,125 --> 00:51:18,093
ASSAY AT ONE POINT IN TIME IS

1618
00:51:18,093 --> 00:51:19,528
GOING TO BE DIFFICULT TO DEPLOY

1619
00:51:19,528 --> 00:51:21,463
IN A TRIAL WHEREAS IF WHAT WE'RE

1620
00:51:21,463 --> 00:51:23,365
PLANNING ON DOING IS USING DAY

1621
00:51:23,365 --> 00:51:25,200
ZERO THROUGH EIGHT AND IDENTIFY

1622
00:51:25,200 --> 00:51:27,903
WHETHER OR NOT TRENDS ARE

1623
00:51:27,903 --> 00:51:29,437
ASSOCIATED WITH THAT PEAK SCAI

1624
00:51:29,437 --> 00:51:30,672
SHOCK STAGE THAT'S COMING, COULD

1625
00:51:30,672 --> 00:51:32,140
YOU GET SOMEBODY'S ATTENTION

1626
00:51:32,140 --> 00:51:32,874
SOMEWHERE ELSE EARLIER.

1627
00:51:32,874 --> 00:51:34,176
SO I WOULD IMAGINE, BECAUSE WE

1628
00:51:34,176 --> 00:51:36,545
HAVE A LOT OF LEVEL 2 CICUs,

1629
00:51:36,545 --> 00:51:39,314
WHICH WE SHOWED IN PARTNER

1630
00:51:39,314 --> 00:51:40,448
CICUs WHICH ARE SHOWN ON THAT

1631
00:51:40,448 --> 00:51:42,083
MAP ESPECIALLY THROUGHOUT

1632
00:51:42,083 --> 00:51:43,618
CALIFORNIA WHERE THE VOLUME OF

1633
00:51:43,618 --> 00:51:45,153
CARDIOGENIC SHOCK IS QUITE HIGH

1634
00:51:45,153 --> 00:51:47,055
AND WE'RE WORKING ON A STUDY TO

1635
00:51:47,055 --> 00:51:48,156
REALLY DEMONSTRATE THAT, THE

1636
00:51:48,156 --> 00:51:49,691
MAJORITY OF CARDIOGENIC SHOCK IS

1637
00:51:49,691 --> 00:51:51,726
NOT SEEN IN TERTIARY CENTERS.

1638
00:51:51,726 --> 00:51:53,495
IT'S SEEN IN COMMUNITY CENTERS

1639
00:51:53,495 --> 00:51:54,896
WHO HAVE TO SEND A LOT OF THESE

1640
00:51:54,896 --> 00:51:59,000
PATIENTS OUT.

1641
00:51:59,000 --> 00:52:00,635
SO IF YOU START TRYING TO FIND

1642
00:52:00,635 --> 00:52:02,404
PARTNER CENTERS WHERE YOU COULD

1643
00:52:02,404 --> 00:52:04,739
CREATE A CARE ALGORITHM AND

1644
00:52:04,739 --> 00:52:06,474
RANDOMIZE PEOPLE DIAGNOSED WITH

1645
00:52:06,474 --> 00:52:09,010
HEART FAIL INTO A -- PATHWAY AND

1646
00:52:09,010 --> 00:52:09,978
NOT AND THEN FOLLOW THEM, THAT

1647
00:52:09,978 --> 00:52:11,780
IS WHERE I THINK WE WOULD END UP

1648
00:52:11,780 --> 00:52:13,114
FINDING EFFICACY AND ALSO MOVING

1649
00:52:13,114 --> 00:52:14,950
FURTHER DOWN THE PATIENT

1650
00:52:14,950 --> 00:52:19,921
EXPERIENCE LADDER.

1651
00:52:19,921 --> 00:52:20,722
 THE EARLIER

1652
00:52:20,722 --> 00:52:22,023
YOU IDENTIFY THESE PATIENTS, A

1653
00:52:22,023 --> 00:52:23,358
THAT'S BETTER FOR THE THE

1654
00:52:23,358 --> 00:52:25,694
PATIENT, BUT B YOU HAVE LESS

1655
00:52:25,694 --> 00:52:27,195
TOOLS TO REPLACE THE ASSAY.

1656
00:52:27,195 --> 00:52:29,397
WE SEE THE MOST EFFECT IN

1657
00:52:29,397 --> 00:52:32,300
PREDICTIVE VALUE IN B AND C, BUT

1658
00:52:32,300 --> 00:52:33,401
BY THE TIME YOU GET TO D,

1659
00:52:33,401 --> 00:52:34,302
EVERYBODY KNOWS YOU'RE SICK,

1660
00:52:34,302 --> 00:52:34,703
RIGHT?

1661
00:52:34,703 --> 00:52:37,172
YOU DON'T NEED A WEATHER VANE TO

1662
00:52:37,172 --> 00:52:38,707
SAY THE WIND IS BLOWING.

1663
00:52:38,707 --> 00:52:39,708
IT WINDY.

1664
00:52:39,708 --> 00:52:41,176
SO WHEN YOU'RE GETTING -- MOVING

1665
00:52:41,176 --> 00:52:43,278
THE TECHNOLOGY, THE MORE THE

1666
00:52:43,278 --> 00:52:44,145
FIDELITY DIFFERENTIATES AT THE

1667
00:52:44,145 --> 00:52:45,880
EARLY PHASES OF DISEASE, THE

1668
00:52:45,880 --> 00:52:47,382
MORE PROMISING IT IS IN MY MIND

1669
00:52:47,382 --> 00:52:50,318
AND THAT BECOMES EASIER TO START

1670
00:52:50,318 --> 00:52:52,087
DEPLOYING IN THE COMMUNITY OR

1671
00:52:52,087 --> 00:52:53,154
TESTING THE COMMUNITY BECAUSE

1672
00:52:53,154 --> 00:52:55,757
THAT PATIENT POPULATION IS HUGE.

1673
00:52:55,757 --> 00:52:58,493
ONE OTHER THING DR. AGBOR DID

1674
00:52:58,493 --> 00:53:01,196
NOT SAY OUTRIGHT IS THAT THE

1675
00:53:01,196 --> 00:53:03,365
CELL-FREE DNA IS ALSO A CLIA

1676
00:53:03,365 --> 00:53:09,037
APPROVED LAB.

1677
00:53:09,037 --> 00:53:10,805
IT'S SOMETHING THAT'S KIND OF

1678
00:53:10,805 --> 00:53:11,773
READY TO GO.

1679
00:53:11,773 --> 00:53:12,841
SO YOU'RE LOOKING AT A

1680
00:53:12,841 --> 00:53:14,175
TECHNOLOGY THAT COULD ACTUALLY

1681
00:53:14,175 --> 00:53:15,477
START BEING DISSEMINATED

1682
00:53:15,477 --> 00:53:15,777
POTENTIALLY.

1683
00:53:15,777 --> 00:53:19,114
SO THERE'S LOTS OF THINGS ABOUT

1684
00:53:19,114 --> 00:53:20,949
IT THAT I THINK IS RIPE FOR USE,

1685
00:53:20,949 --> 00:53:22,050
DEPLOYABLE IN MEDICAL CENTERS

1686
00:53:22,050 --> 00:53:23,118
AND THAT'S WHERE I THINK WE

1687
00:53:23,118 --> 00:53:24,219
WOULD START TARGETING PEOPLE TO

1688
00:53:24,219 --> 00:53:25,186
SHOW BENEFIT.

1689
00:53:25,186 --> 00:53:27,589
>> THANK YOU FOR THE TALK.

1690
00:53:27,589 --> 00:53:31,393
I WANT TO GET YOUR THOUGHTS LIKE

1691
00:53:31,393 --> 00:53:32,694
WE'VE BEEN -- IN THIS STUDY WE

1692
00:53:32,694 --> 00:53:36,631
USE IT AS A BIOMARKER RISK

1693
00:53:36,631 --> 00:53:37,699
STRATIFICATION, DO YOU SEE IT AS

1694
00:53:37,699 --> 00:53:39,668
A VENUE TO BE USED AS A MARKER

1695
00:53:39,668 --> 00:53:42,504
FOR RESPONSE TO TREATMENT, TO

1696
00:53:42,504 --> 00:53:44,606
THERAPIES AS DRUGS OR MECHANICAL

1697
00:53:44,606 --> 00:53:47,842
SUPPORT?

1698
00:53:47,842 --> 00:53:49,444
>> I'LL TAKE THAT ONE.

1699
00:53:49,444 --> 00:53:53,048
SO THE SHORT ANSWER IS YES,

1700
00:53:53,048 --> 00:53:53,782
ABSOLUTELY.

1701
00:53:53,782 --> 00:53:55,317
WE HAVEN'T YET DONE THIS IN THIS

1702
00:53:55,317 --> 00:53:57,419
COHORT WHERE WE'VE TAKEN THE

1703
00:53:57,419 --> 00:53:58,353
LONGITUDINAL SAMPLES

1704
00:53:58,353 --> 00:53:59,487
>> D

1705
00:53:59,487 --> 00:54:04,259
>>SAMPLE IS ANDANALYZED
THEM YEE

1706
00:54:04,259 --> 00:54:05,493
TAKEN SAMPLES, LOOK AT THEM

1707
00:54:05,493 --> 00:54:07,262
BEFORE AND AFTER AND SEE THEIR

1708
00:54:07,262 --> 00:54:09,230
CELL-FREE DNA LEVELS TRACKS IN

1709
00:54:09,230 --> 00:54:10,965
COWARD YAITION WITH AT LEAST

1710
00:54:10,965 --> 00:54:14,002
THEIR PHYSIOLOGY NUMBERS, RIGHT

1711
00:54:14,002 --> 00:54:15,203
ATRIAL PRESSURES AND WHATNOT.

1712
00:54:15,203 --> 00:54:16,671
SO I THINK THERE IS SOME PROMISE

1713
00:54:16,671 --> 00:54:18,907
IN USING CELL-FREE DNA TO TRACK

1714
00:54:18,907 --> 00:54:20,308
THE EFFICACY OF CERTAIN

1715
00:54:20,308 --> 00:54:22,110
TREATMENTS LIKE MCS, AND I'M

1716
00:54:22,110 --> 00:54:23,345
HOPING THAT, YOU KNOW, ONCE WE

1717
00:54:23,345 --> 00:54:25,413
GET OUR NUMBERS HIGHER UP IN

1718
00:54:25,413 --> 00:54:26,548
THIS THAT WE'RE GOING TO BE ABLE

1719
00:54:26,548 --> 00:54:27,449
TO LOOK AT THAT A LITTLE BIT

1720
00:54:27,449 --> 00:54:30,852
MORE DEEPLY.

1721
00:54:30,852 --> 00:54:36,291
>> IF I MAY ALSO, YOU CAN
USE TO

1722
00:54:36,291 --> 00:54:36,591
TRACK.

1723
00:54:36,591 --> 00:54:37,892
THE OTHER THING THAT WE COULD

1724
00:54:37,892 --> 00:54:41,629
ALSO USE THIS FOR IS IF YOU

1725
00:54:41,629 --> 00:54:42,831
THINK ABOUT THE CELL-FREE DNA,

1726
00:54:42,831 --> 00:54:44,966
THERE'S QUITE A BIT OF DATA NOW

1727
00:54:44,966 --> 00:54:47,369
THAT'S COMING OUT SHOWING THAT

1728
00:54:47,369 --> 00:54:49,571
THE CELL-FREE DNA IS NOT JUST

1729
00:54:49,571 --> 00:54:50,538
FLOATING AROUND IN THE

1730
00:54:50,538 --> 00:54:51,039
CIRCULATION.

1731
00:54:51,039 --> 00:54:53,475
IT COULD BE A POTENTIAL DAMAGE

1732
00:54:53,475 --> 00:54:55,977
ASSOCIATED MOLECULAR PATTERN.

1733
00:54:55,977 --> 00:54:57,679
WHICH ON THE RECEPTORS OR THE

1734
00:54:57,679 --> 00:55:02,917
PATHWAYS OF THESE DAM IF YOU MAY

1735
00:55:02,917 --> 00:55:04,252
CALL THOSE HAVE BEEN REALLY WELL

1736
00:55:04,252 --> 00:55:04,586
MAPPED OUT.

1737
00:55:04,586 --> 00:55:06,721
IN THE LAST FEW YEARS, THERE

1738
00:55:06,721 --> 00:55:08,990
HAVE BEEN SOME NICE MONOCLONAL

1739
00:55:08,990 --> 00:55:10,225
ANTIBODIES THAT HAVE BEEN

1740
00:55:10,225 --> 00:55:13,661
DEVELOPED TARGETING THESE

1741
00:55:13,661 --> 00:55:13,928
PATHWAYS.

1742
00:55:13,928 --> 00:55:16,164
ASHLEY HAS SOME DATA ON LVAD

1743
00:55:16,164 --> 00:55:17,365
PATIENTS WHICH SHOW THAT THOSE

1744
00:55:17,365 --> 00:55:20,168
PATIENTS WHO HAVE REALLY HIGH

1745
00:55:20,168 --> 00:55:22,137
CELL-FREE DNA DERIVED FROM

1746
00:55:22,137 --> 00:55:23,238
NEUTROPHILS, DERIVED FROM SOME

1747
00:55:23,238 --> 00:55:26,641
OF THESE OTHER PATHWAYS, SOME OF

1748
00:55:26,641 --> 00:55:29,077
THESE OTHER INNATE IMMUNE CELLS,

1749
00:55:29,077 --> 00:55:30,512
THOSE PATIENTS SEEM TO HAVE THE

1750
00:55:30,512 --> 00:55:31,279
WORST OUTCOMES.

1751
00:55:31,279 --> 00:55:34,182
THE QUESTION THEN BECOMES IS

1752
00:55:34,182 --> 00:55:35,617
CELL-FREE DNA ALSO CONTRIBUTING

1753
00:55:35,617 --> 00:55:37,786
TO THE PROGRESSION OF THIS

1754
00:55:37,786 --> 00:55:39,988
DISEASE, NOT JUST AS A BIOMARKER

1755
00:55:39,988 --> 00:55:42,891
TO TRACK THE DISEASE, BUT AS A

1756
00:55:42,891 --> 00:55:44,526
PATHOGEN, IF YOU MAY USE SUCH A

1757
00:55:44,526 --> 00:55:45,527
WORD, CONTRIBUTING TO THAT

1758
00:55:45,527 --> 00:55:46,795
DISEASE.

1759
00:55:46,795 --> 00:55:50,732
AND THEREFORE BY TARGETING THESE

1760
00:55:50,732 --> 00:55:53,468
PATHWAYS, COULD YOU THEN

1761
00:55:53,468 --> 00:55:54,669
ALLEVIATE THESE UNFORTUNATE

1762
00:55:54,669 --> 00:55:55,770
PATIENTS FROM THESE

1763
00:55:55,770 --> 00:55:56,704
COMPLICATIONS.

1764
00:55:56,704 --> 00:55:59,340
SO THAT'S HOPEFULLY THAT ALSO

1765
00:55:59,340 --> 00:56:02,277
OPENS UP THIS AREA OF RESEARCH.

1766
00:56:02,277 --> 00:56:02,610
WE'LL SEE.

1767
00:56:02,610 --> 00:56:04,712
THANK YOU.

1768
00:56:04,712 --> 00:56:07,749
>> HAVE YOU APPLIED
MACHINE

1769
00:56:07,749 --> 00:56:09,684
LEARNING TO THE ANALYSIS OF THE

1770
00:56:09,684 --> 00:56:11,753
BIOMARKERS, OR HAS IT BEEN MOST

1771
00:56:11,753 --> 00:56:13,021
LEHIGH POTASSIUM CYST-DRIVEN SO

1772
00:56:13,021 --> 00:56:19,527
MOSTLY HYPOTHESIS-DRIVEN SO FAR?

1773
00:56:19,527 --> 00:56:21,396
>> YOU JUST STICK MY
EXCITEMENT

1774
00:56:21,396 --> 00:56:22,831
THERE QUITE A BIT.

1775
00:56:22,831 --> 00:56:24,566
SO THE ANSWER IS NO.

1776
00:56:24,566 --> 00:56:28,036
WE'VE BEEN THINKING ABOUT THIS

1777
00:56:28,036 --> 00:56:30,104
IN A VERY LINEAR WAY.

1778
00:56:30,104 --> 00:56:31,973
BUT THERE COMES -- I BELIEVE

1779
00:56:31,973 --> 00:56:35,276
SOME OF THE ADVANTAGES OF REALLY

1780
00:56:35,276 --> 00:56:36,611
GETTING A BUNCH OF RESEARCHERS

1781
00:56:36,611 --> 00:56:39,047
IN THE SAME SAND BOX.

1782
00:56:39,047 --> 00:56:44,619
I RUN INTO -- JAI IN THE

1783
00:56:44,619 --> 00:56:46,654
HALLWAY, TRUE STORY, AND SHE IS

1784
00:56:46,654 --> 00:56:47,856
PUTTING TOGETHER A MULTI-OMIC

1785
00:56:47,856 --> 00:56:49,891
BASED APPROACH TO LOOK AT

1786
00:56:49,891 --> 00:56:51,092
ANOTHER HETEROGENEOUS DISEASE,

1787
00:56:51,092 --> 00:56:53,394
WHICH IS HEART FAILURE IN THE

1788
00:56:53,394 --> 00:56:54,496
COMMUNITY NOW.

1789
00:56:54,496 --> 00:56:56,965
THAT'S WHERE I LEARNED ABOUT THE

1790
00:56:56,965 --> 00:57:00,802
POWER OF HOW YOU CAN INTEGRATE

1791
00:57:00,802 --> 00:57:03,104
ALL THESE NICE DATASETS INTO A

1792
00:57:03,104 --> 00:57:08,176
SINKSINGLE PLATFORM AND USE MACE

1793
00:57:08,176 --> 00:57:10,278
LEARNING TO THEN GET BETTER BANG

1794
00:57:10,278 --> 00:57:12,080
FOR YOUR BUCK THAN SINGLE

1795
00:57:12,080 --> 00:57:13,715
MODALITY APPROACHES.

1796
00:57:13,715 --> 00:57:14,749
SO THROUGH HER, WE'RE BEGINNING

1797
00:57:14,749 --> 00:57:15,350
TO LEARN THAT.

1798
00:57:15,350 --> 00:57:16,551
THEN WE'VE ALSO BEEN VERY

1799
00:57:16,551 --> 00:57:19,387
FORTUNATE THAT WE FOUND A

1800
00:57:19,387 --> 00:57:22,657
WONDERFUL STATISTICIAN WITH THAT

1801
00:57:22,657 --> 00:57:25,159
EXPERIENCE, SHEN CHANG AT NHLBI.

1802
00:57:25,159 --> 00:57:26,127
SO IF YOU HOLD THAT QUESTION AND

1803
00:57:26,127 --> 00:57:28,096
ASK US THAT NEXT YEAR, MAYBE

1804
00:57:28,096 --> 00:57:29,964
WE'LL BE ABLE TO GIVE YOU A

1805
00:57:29,964 --> 00:57:30,832
BETTER ANSWER.

1806
00:57:30,832 --> 00:57:32,100
BUT WE BELIEVE THAT MAYBE WE

1807
00:57:32,100 --> 00:57:35,537
SHOULD BE ABLE TO -- THE SYSTEM

1808
00:57:35,537 --> 00:57:37,472
BY USING MACHINE LEARNING MODELS

1809
00:57:37,472 --> 00:57:38,840
TO IMPROVE THEM.

1810
00:57:38,840 --> 00:57:41,142
>> I'D ALSO LIKE TO PUT IN
A

1811
00:57:41,142 --> 00:57:42,677
PLUG FOR THE AI WORKSHOP ON

1812
00:57:42,677 --> 00:57:42,911
FRIDAY.

1813
00:57:42,911 --> 00:57:43,711
>> OH.

1814
00:57:43,711 --> 00:57:44,712
EVERYBODY, AI WORKSHOP ON

1815
00:57:44,712 --> 00:57:47,115
FRIDAY.

1816
00:57:47,115 --> 00:57:48,750
>> ONE THING I WANTED TO
THROW

1817
00:57:48,750 --> 00:57:51,152
IN THERE FOR MACHINE LEARNING,

1818
00:57:51,152 --> 00:57:52,654
ONE OF THE SIGNIFICANT

1819
00:57:52,654 --> 00:57:54,188
CHALLENGES THAT EXISTS FOR A LOT

1820
00:57:54,188 --> 00:57:57,358
OF MCS RESEARCH AND SHOCK

1821
00:57:57,358 --> 00:58:01,362
RESEARCH IS THE PHENOTYPING IS

1822
00:58:01,362 --> 00:58:02,664
NOT CONSISTENT.

1823
00:58:02,664 --> 00:58:04,966
SO IF YOU LOOK AT DIFFERENT

1824
00:58:04,966 --> 00:58:06,067
REGISTRIES, SCAI SHOCK HAS

1825
00:58:06,067 --> 00:58:08,636
SLIGHTLY DIFFERENT DE DEFINITIOS

1826
00:58:08,636 --> 00:58:10,171
ACROSS DIFFERENT REGISTRIES.

1827
00:58:10,171 --> 00:58:11,039
SO ONE CHALLENGE THAT THE FIELD

1828
00:58:11,039 --> 00:58:13,074
HAS WHEN YOU START POOLING THIS

1829
00:58:13,074 --> 00:58:14,409
TOGETHER, EVEN THOUGH THE SAME

1830
00:58:14,409 --> 00:58:16,044
LETTER VALUE IS ATTACHED TO

1831
00:58:16,044 --> 00:58:17,312
SPECIFIC PATIENTS, ALL OF A

1832
00:58:17,312 --> 00:58:20,048
SUDDEN YOU'RE GOING TO HAVE SOME

1833
00:58:20,048 --> 00:58:20,315
VARIATION.

1834
00:58:20,315 --> 00:58:21,482
AND THE OTHER THING THAT'S

1835
00:58:21,482 --> 00:58:24,552
REALLY TRICKY IS THAT SCAI SHOCK

1836
00:58:24,552 --> 00:58:26,487
STAGE, BECAUSE IT'S ALL DONE AT

1837
00:58:26,487 --> 00:58:28,022
THE REGISTRY LEVEL THUS FAR,

1838
00:58:28,022 --> 00:58:31,292
THERE ARE RULES FOR YOUR SCAI

1839
00:58:31,292 --> 00:58:32,927
SHOCK STAGING BUT I'M WILLING TO

1840
00:58:32,927 --> 00:58:34,629
BET AT SOME POINT IN THE FAR OFF

1841
00:58:34,629 --> 00:58:35,830
FUTURE, WE WILL FIND IT IS

1842
00:58:35,830 --> 00:58:36,998
IMPOSSIBLE TO DIVORCE WHAT WE

1843
00:58:36,998 --> 00:58:38,433
KNOW ABOUT THE PATIENTS FROM OUR

1844
00:58:38,433 --> 00:58:41,269
ASSESSMENTS OF THEIR ACUTITY AND

1845
00:58:41,269 --> 00:58:43,905
UNDERSTANDING WHAT THEIR

1846
00:58:43,905 --> 00:58:44,439
TRAJECTORY WAS.

1847
00:58:44,439 --> 00:58:46,174
THERE ARE A LOT OF THINGS ABOUT

1848
00:58:46,174 --> 00:58:48,242
AMYLOID PATIENTS WILL HAVE

1849
00:58:48,242 --> 00:58:49,611
NORMAL SIZED VENTRICLES AND IF

1850
00:58:49,611 --> 00:58:51,946
YOU GO THROUGH AN AI MODEL,

1851
00:58:51,946 --> 00:58:54,449
THEY'RE GOING TO BE VERY DIFFER

1852
00:58:54,449 --> 00:58:55,550
TO DIFFERENTIATE FROM PEOPLE

1853
00:58:55,550 --> 00:58:57,752
WITH HEALTHY VENTRICLES.

1854
00:58:57,752 --> 00:58:59,120
SO YOU HAVE TO BE REALLY CAREFUL

1855
00:58:59,120 --> 00:59:00,221
THAT YOU'RE GOING TO LOSE

1856
00:59:00,221 --> 00:59:02,523
SPECIFIC SIGNALS BY HIGH RISK

1857
00:59:02,523 --> 00:59:04,158
PHYSIOLOGY BY BURYING IT AGAINST

1858
00:59:04,158 --> 00:59:06,127
THINGS THAT LOOK SIMILAR BY SOME

1859
00:59:06,127 --> 00:59:08,029
METRICS, AND REALLY ENCOURAGE

1860
00:59:08,029 --> 00:59:09,530
PEOPLE WHO WANT TO LEARN ABOUT

1861
00:59:09,530 --> 00:59:11,899
THIS VERY MUCH LIKE WE HAVE, IS

1862
00:59:11,899 --> 00:59:13,968
BE ULTRA SPECIFIC AND HANDLE THE

1863
00:59:13,968 --> 00:59:15,703
DATA YOURSELF AND ASK YOUR

1864
00:59:15,703 --> 00:59:18,640
QUESTION IN A VERY, VERY, VERY

1865
00:59:18,640 --> 00:59:19,741
TARGETED WAY BEFORE WE START

1866
00:59:19,741 --> 00:59:20,908
GETTING TOO DIFFUSE.

1867
00:59:20,908 --> 00:59:21,909
BECAUSE I FEEL LIKE WE'RE GOING

1868
00:59:21,909 --> 00:59:23,344
TO GET OURSELVES LOST IN THE

1869
00:59:23,344 --> 00:59:24,846
WEEDS CHASING THE GOLD AT THE

1870
00:59:24,846 --> 00:59:26,147
END OF THE RAINBOW BEFORE WE'VE

1871
00:59:26,147 --> 00:59:27,448
EVEN STARTED IN A MEANINGFUL

1872
00:59:27,448 --> 00:59:30,652
WAY.

1873
00:59:30,652 --> 00:59:31,185
>> HI.

1874
00:59:31,185 --> 00:59:33,121
THANK YOU SO MUCH FOR

1875
00:59:33,121 --> 00:59:33,454
PRESENTATION.

1876
00:59:33,454 --> 00:59:34,622
I THOUGHT IT WAS MARVELOUS.

1877
00:59:34,622 --> 00:59:35,823
I HAVE TWO QUESTIONS, MAYBE

1878
00:59:35,823 --> 00:59:36,290
THREE.

1879
00:59:36,290 --> 00:59:38,326
THE FIRST QUESTION IS, ONE OF

1880
00:59:38,326 --> 00:59:40,995
THE SLIDES THAT DR. PARK SHOWED,

1881
00:59:40,995 --> 00:59:43,598
THERE WAS DEFINITELY A

1882
00:59:43,598 --> 00:59:45,333
DIFFERENCE BETWEEN SORT OF THE

1883
00:59:45,333 --> 00:59:49,003
PATIENTS WITH HIGHER NUCLEAR

1884
00:59:49,003 --> 00:59:50,471
CELL-FREE DNA AS WELL AS MIGHT

1885
00:59:50,471 --> 00:59:52,640
CON DREE A I BELIEVE SUBSEQUENT

1886
00:59:52,640 --> 00:59:54,042
SLIDES ALSO SHOW NUCLEAR

1887
00:59:54,042 --> 00:59:54,609
CELL-FREE DNA.

1888
00:59:54,609 --> 00:59:59,480
AND I WONDER THERE'S CORRELATION

1889
00:59:59,480 --> 01:00:01,449
SUBSEQUENTLY EVEN WITH THE

1890
01:00:01,449 --> 01:00:03,317
MITOCHONDRIAL CELL-FREE DNA.

1891
01:00:03,317 --> 01:00:06,921
THE SECOND QUESTION WAS, THE

1892
01:00:06,921 --> 01:00:08,890
LAST SLIDE, DR. PARK TALKED

1893
01:00:08,890 --> 01:00:10,758
ABOUT HOW IF YOU HAVE THIS

1894
01:00:10,758 --> 01:00:12,827
CELL-FREE DNA THEN, YOU CAN SORT

1895
01:00:12,827 --> 01:00:14,996
OF TRY TO TRACK THOSE PATIENTS

1896
01:00:14,996 --> 01:00:17,699
EARLY ON WHETHER THEY NEED M CS

1897
01:00:17,699 --> 01:00:18,800
OR OTHER INTERVENTIONS.

1898
01:00:18,800 --> 01:00:21,502
MY QUESTION IS, I WONDER IF YOU

1899
01:00:21,502 --> 01:00:24,105
CAN ALSO USE TO TRACK WHETHER

1900
01:00:24,105 --> 01:00:27,542
PATIENTS HAD REVERSIBLE OR

1901
01:00:27,542 --> 01:00:30,044
IRREVERSIBLE CARDIOGENIC SHOCK.

1902
01:00:30,044 --> 01:00:33,881
I DON'T KNOW IF DR. NATEESON IS

1903
01:00:33,881 --> 01:00:35,616
HERE, BUT HE TAUGHT ME THAT WHEN

1904
01:00:35,616 --> 01:00:37,351
PATIENTS UNDERGO SEPTIC SHOCK,

1905
01:00:37,351 --> 01:00:38,586
THERE IS A CARDIOGENIC INJURY

1906
01:00:38,586 --> 01:00:40,054
COMPONENT AND I WONDER IF THAT

1907
01:00:40,054 --> 01:00:42,356
HAS TO DO WITH WHAT DR. AGBOR

1908
01:00:42,356 --> 01:00:45,626
SAID ABOUT NEUTROPHILS AS A

1909
01:00:45,626 --> 01:00:47,128
CELL-FREE DNA PATHOGENIC PATHWAY

1910
01:00:47,128 --> 01:00:48,896
OR WHETHER IT HAS TO DO WITH

1911
01:00:48,896 --> 01:00:53,534
CERTAIN SORT OF THE CELLS WITHIN

1912
01:00:53,534 --> 01:00:53,935
THE HEART.

1913
01:00:53,935 --> 01:00:55,970
SO I WONDER IF CELL-FREE DNA

1914
01:00:55,970 --> 01:00:58,806
WOULD HAVE POTENTIAL TO SORT OF

1915
01:00:58,806 --> 01:00:59,574
DECIPHER THAT AS WELL.

1916
01:00:59,574 --> 01:01:01,209
AND THEN THE THIRD QUESTION I

1917
01:01:01,209 --> 01:01:04,011
GUESS IS, IF WE GET TO A WAY

1918
01:01:04,011 --> 01:01:05,980
WHERE IF IT'S JUST LIKE A BLOOD

1919
01:01:05,980 --> 01:01:08,616
DRAW, WHETHER WE CAN APPLY THIS

1920
01:01:08,616 --> 01:01:09,884
IN SORT OF RESOURCE LIMITED

1921
01:01:09,884 --> 01:01:11,886
SETTINGS NOT JUST IN CARDIOGENIC

1922
01:01:11,886 --> 01:01:13,955
SHOCK, BUT SEPTIC SHOCK, BECAUSE

1923
01:01:13,955 --> 01:01:16,624
YOU KNOW, MORTALITY AS WE KNOW

1924
01:01:16,624 --> 01:01:19,160
WITH SEPTIC SHOCK IS 50% OR

1925
01:01:19,160 --> 01:01:20,795
GREATER AND IN DEVELOPING

1926
01:01:20,795 --> 01:01:21,662
COUNTRIES IT'S HIGHER.

1927
01:01:21,662 --> 01:01:27,468
SO THOSE ARE MY THREE QUESTIONS.

1928
01:01:27,468 --> 01:01:28,703
>> I'LL START WITH THE
FIRST

1929
01:01:28,703 --> 01:01:30,304
QUESTION WHICH IS MITOCHONDRIAL

1930
01:01:30,304 --> 01:01:32,907
CELL-FREE DNA AND WHY WE HAVEN'T

1931
01:01:32,907 --> 01:01:34,075
FEATURED THAT.

1932
01:01:34,075 --> 01:01:35,743
SO WE HAVE LOOKED AT

1933
01:01:35,743 --> 01:01:36,511
MITOCHONDRIAL DNA IN ASSOCIATION

1934
01:01:36,511 --> 01:01:39,547
WITH THESE SORT OF OUTCOMES.

1935
01:01:39,547 --> 01:01:41,315
IN GENERAL, RELATIONSHIP WITH

1936
01:01:41,315 --> 01:01:43,284
NUCLEAR CELL-FREE DNA AND THE

1937
01:01:43,284 --> 01:01:46,654
PROGRESSION IN DEATH IS OVERALL

1938
01:01:46,654 --> 01:01:48,623
STRONGER THAN MITOCHONDRIAL

1939
01:01:48,623 --> 01:01:49,357
CELL-FREE DNA.

1940
01:01:49,357 --> 01:01:51,659
I THINK ALSO FLAD OUR FOCUS HAS

1941
01:01:51,659 --> 01:01:54,262
BEEN ON NUCLEAR CELL-FREE DNA

1942
01:01:54,262 --> 01:01:56,898
BECAUSE A LOT OF OUR TISSUE

1943
01:01:56,898 --> 01:01:58,099
SPECIFIC RELIES ON NUCLEAR

1944
01:01:58,099 --> 01:02:00,635
DURAN, SO THAT IS MAINLY THE

1945
01:02:00,635 --> 01:02:01,369
REASON FOR WHY THAT WAS

1946
01:02:01,369 --> 01:02:01,702
FEATURED.

1947
01:02:01,702 --> 01:02:04,105
BUT YES, IT'S A FANTASTIC

1948
01:02:04,105 --> 01:02:07,041
QUESTION OF MIG MITOCHONDRIAL

1949
01:02:07,041 --> 01:02:08,009
CELL-FREE DNA AND WHETHER THAT

1950
01:02:08,009 --> 01:02:09,177
HAS ANY ROLE IN CARDIOGENIC

1951
01:02:09,177 --> 01:02:10,511
SHOCK AS WELL.

1952
01:02:10,511 --> 01:02:14,749
BUT THAT'S TO COME.

1953
01:02:14,749 --> 01:02:16,818
>> CAN I SAY, IF YOU DON'T
MIND,

1954
01:02:16,818 --> 01:02:18,152
WE'LL TAKE THE REST OF YOUR

1955
01:02:18,152 --> 01:02:20,555
QUESTIONS IMMEDIATELY AFTER

1956
01:02:20,555 --> 01:02:22,290
THIS, BECAUSE FOR THE SAKE OF

1957
01:02:22,290 --> 01:02:24,358
TIME, IT'S A LITTLE -- 1 MINUTE

1958
01:02:24,358 --> 01:02:25,660
PAST THE HOUR, I WANT TO MAKE

1959
01:02:25,660 --> 01:02:26,761
SURE WE GIVE EVERYBODY THEIR

1960
01:02:26,761 --> 01:02:27,395
TIME BACK.

1961
01:02:27,395 --> 01:02:30,231
BUT REALLY THANK YOU FOR COMING

1962
01:02:30,231 --> 01:02:33,968
DOWN TO LISTEN TO ASHLEY AND TO

1963
01:02:33,968 --> 01:02:36,437
LISTEN TO DR. CONNOR, AND IF YOU

1964
01:02:36,437 --> 01:02:38,539
DO NOT MIND, YOU KNOW, AS A

1965
01:02:38,539 --> 01:02:39,841
MENTOR, SOMETIMES IT GREAT IF

1966
01:02:39,841 --> 01:02:42,043
YOU'RE CLAPPING FOR THE TRAINEE,

1967
01:02:42,043 --> 01:02:46,848
BUT IF YOU DO NOT MIND, VERY

1968
01:02:46,848 --> 01:02:49,116
KINDLY JOIN ME IN CLAPPING FOR

1969
01:02:49,116 --> 01:02:50,451
DR. CONNOR COMING ALL THE WAY

1970
01:02:50,451 --> 01:02:51,953
FROM UCSF TO VISIT US HERE.

1971
01:02:51,953 --> 01:02:53,487
HE'S GOING TO BE HERE FOR TWO

1972
01:02:53,487 --> 01:02:59,060
DAYS, AND ALSO REALLY WHAT COULD

1973
01:02:59,060 --> 01:03:01,229
GIVE A MENTOR SO MUCH JOY THAN

1974
01:03:01,229 --> 01:03:02,630
TO STAND AND CLAP FOR ASHLEY AS

1975
01:03:02,630 --> 01:03:02,830
WELL.

1976
01:03:02,830 --> 01:03:03,531
THANK YOU.

1977
01:03:03,531 --> 01:03:09,971
[APPLAUSE]

1978
01:03:09,971 --> 01:03:20,314
THANK YOU VERY MUCH.