Demystifying Medicine 2016: Progress in Understanding Congenital Heart Disease

Demystifying Medicine 2016: Progress in Understanding Congenital Heart Disease


>>OKAY. SO GOOD AFTERNOON. WE’LL BEGIN AND THE ONLY THING I WOULD MENTION FOR THOSE OF YOU WHO HAPPEN TO HAVE BEEN TO ONE OF THESE SESSIONS, WE ENCOURAGE YOU TO ASK QUESTIONS, INTERRUPT IN THE MIDDLE OF A TALK BUT THERE WILL BE TIME AT THE END OF EACH AND AT THE FINAL, THE ONE THING I WOULD ASK IS JUST WAIT UNTIL WE CAN GET A MICROPHONE TO YOU BECAUSE THERE ARE LOTS AND LOTS OF PEOPLE BETWEEN 2 AND 400, BELIEVE IT OR NOT, EACH WEEK, WHO DOWNLOAD THIS HERE ON THE NIH CAMPUS, AND THEY SEND ME EMAILS SAYING WE OFTEN HEAR THE ANSWERS BUT WE DON’T KNOW WHAT THE QUESTIONS ARE SOMETIMES. SO JUST BE A LITTLE BIT PATIENT. AND THE OTHER THING I’D MENTION IS RECALL I POINTED OUT THE SCHEDULE HAD CHANGED, AND SO NEXT WEEK IS THE ORAL MICROBIOME MEETS CELL BIOLOGY AND PERIODONTAL DISEASE. IT’S INCREDIBLY EXCITING WORK, AND I HOPE ALL OF YOU WILL COME. LET’S SEE. YOU HAVEN’T BEEN HERE BEFORE. SO WHAT IS THIS PICTURE?>>[INAUDIBLE]>>RIGHT. WHAT ABOUT — ANYBODY KNOW WHAT IT IS? WHAT IS IT? SURE, IT’S THE BROOKLYN BRIDGE. SO WHY DO WE SHOW THE BROOKLYN BRIDGE? BECAUSE IT’S A WONDERFUL ADVERTISEMENT FOR THE PURPOSE OF THIS WHOLE COURSE, WHICH IS TO BRIDGE TWO THINGS. ONE, THE INCREDIBLE ADVANCES IN BASIC BIOLOGICAL AND ENGINEERING SCIENCES, AND THE OTHER IS WITH DISEASE MECHANISMS, TREATMENT AND SO FORTH. THAT’S ONE OF THE BIG GAPS THAT EXISTS IN MEDICINE AND SCIENCE TODAY, SO THIS COURSE IS ONE SMALL STEP BECAUSE MOST OF THE PEOPLE WHO ATTEND EITHER HERE OR ONLINE ARE PH.D. SCIENTISTS WHO KNOW RELATIVELY LITTLE ABOUT DISEASE AND DISEASE MECHANISMS, BUT A GREAT DEAL ABOUT — SCIENCE OF ONE FORM OR ANOTHER. SO JUST FOR THE RECORD, THAT’S MANHATTAN ON THE OTHER SIDE, AND THIS IS BROOKLYN, AND THOSE GENTLEMEN AND LADIES CAN WALK OUT ON THE CATWALK, SO THAT’S WHERE WE’RE GOING TODAY. WE’RE GOING TO WALK OUT ON THE CATWALK ONCE AGAIN OF CONGENITAL HEART DISEASE THIS TIME. AND SO THE PURPOSE IS TO EXCITE YOU ABOUT EXCITING THINGS THAT ARE GOING ON. THIS IS NOT INTENDED TO BE LIKE A MEDICAL SCHOOL OR EVEN GRADUATE SCHOOL LECTURE WHERE PEOPLE ARE SUPPOSED TO TAKE COPIOUS NOTES AND MEMORIZE A LOT. FOR THOSE WHO COME TO AT LEAST 50% OF THE THINGS AND SIGN IN, AND TAKE A VERY, VERY DIFFICULT, I ASSURE YOU IT’S NOT — ELECTRONIC EXAM AT THE END, YOU GET A CERTIFICATE FROM THE NIH FOR HAVING TAKEN THIS COURSE IN DEMYSTIFYING MEDICINE, AND THAT WILL GUARANTEE A JOB FOR YOU AFTER YOUR POSTDOCTORAL FELLOWSHIP. SO OKAY. SO VERY QUICKLY, I THINK TODAY’S SUBJECT IS REALLY ONE OF THE GREAT ADVANCES IN MEDICINE. YOU CAN SORT OF DIVIDE IT INTO ROUGHLY — THERE IS THE WA THIS
IS THE WAY
A LIVER DOCTOR WOULD DIVIDE IT ANYWAY, INTO THE BEATING HEART ERA, WHEN SURGERY WAS DONE ON THE BEATING HEART. BEGINNING IN A BREADTH TAKING PERFORMANCE IN BOSTON IN 1938, AND THEN PROBABLY THE MOST FAMOUS WOMAN IN AMERICAN MEDICINE, HELEN TAUSIG, WHO I BELIEVE WAS THE FIRST WOMAN PROFESSOR AT JOHNS HOPKINS SCHOOL OF MEDICINE, MAYBE THE ONLY PROFESSOR, I’M NOT SURE ABOUT THAT, BUT SHE WAS CERTAINLY THE FIRST, AND SHE’S AN AMAZING LADY. AND THEN CAME THE AREA WHEN YOU COULD QUIET THE HEART BY GENERATING TECHNIQUES TO BYPASS, IN OTHER WORDS, OPERATE ON A HEART THAT WASN’T ACTUALLY BEATING, AND THAT INITIALLY WAS CROSS CIRCULATION, THEN MACHINES WERE DEVELOPED, AND THEN THE ERA THAT BEGAN WITH THE NOBEL PRIZE IN THE 1930s, BEING ABLE TO CAT TERRIZCATHETERIZE THE HEART
AND MEASURE BLOOD SUPPLY AND EVERYTHING ELSE. SURGICAL ADVANCES INCLUDING TRANSPLANTATION AND OTHER TECHNIQUES, AND THEN HERE WE ARE IN WHAT I WOULD CALL THE BRACE NEBRAVENEW ERA, GENOMICS,
DEVELOPMENT OF PHARMACOLOGIC APPROACHES TO TREATMENT OF CONGENITAL HEART DISEASE AND OTHER DISEASE. INCREDIBLE INPUT OF BIOENGINEERING, WHICH YOU’LL HEAR ABOUT FROM DR. LEDERMAN, AND EVEN POSSIBILITIES OF CONSIDERING SURGERY IN A FETUS. BUT THESE THINGS ARE THINGS THAT WILL BE PRESENTED AND HOPEFULLY STIMULATE YOUR INTEREST. SO OUR FIRST SPEAKER IS GAIL PEARSON, WHO GRADUATED FROM JOHNS HOPKINS IN MEDICINE AND ALSO HAS A DOCTOR OF SCIENCE DEGREE IN PUBLIC HEALTH POLICY. SHE’S A PEDIATRIC CARDIOLOGIST WHO I BELIEVE RECENTLY CAME TO NIH IN YOUR NEW POSITION, RIGHT? AS ASSOCIATE DIRECTOR OF THE DIVISION OF CARDIOVASCULAR SCIENCES, AND SHE’S ALSO DIRECTOR OF THE ADULT AND PEDIATRIC CARDIAC RESEARCH PROGRAM AT THE NIH LBI. WELL, DR. PEARSON HAS EXTENSIVE EXPERIENCE IN RESEARCH AND IN CLINICAL ASPECTS OF CONGENITAL HEART DISEASE. AND SO SHE’S GOING TO SPEAK FIRST. AND THEN SHE’LL BE FOLLOWED BY BOB LEDERMAN, WHO TRAINED AT WESTERN RESERVE SCHOOL OF MEDICINE, AND RECEIVED TRAINING IN ADULT CARDIOLOGY IN SAN FRANCISCO, BECAME — WENT TO THE UNIVERSITY OF MICHIGAN, GOT INTERESTED IN INTERVENTIVE NON-SURGICAL INTERVENTION TYPE OF TECHNOLOGY AND BIOLOGY, WAS AT MICHIGAN, THEN AT DUKE, BACK AT MICHIGAN, AND CAME TO THE HEART INSTITUTE HERE IN 2000 TO BEGIN WORK ON INTERVENTIONAL CARDIOVASCULAR MRI AND OTHER TECHNOLOGIES. SO BOB’S INTEREST IS TO EXPAND THE CAPABILITY, THE SAFETY, THE EFFECTIVENESS OF WAYS OF NON-OPERATIVELY DEALING WITH REALTIME IMAGING AND ALSO SET THE BASIS FOR INTERVENTIVE SURGERY, CORRECTION OF CONGENITAL DEFECTS AND OTHER FLEXIBILITIES. SO CAN WE BEGIN, PLEASE.>>THANK YOU. CAN PEOPLE HEAR ME? I’M DELIGHTED TO HAVE THE OPPORTUNITY TO BE HERE THIS AFTERNOON ALONG WITH MY COLLEAGUE, LAURA, WHO WILL BE HERE. SHE’S STUCK IN TRAFFIC, IS ABOUT 15 OR 20 MINUTES AWAY AND SHE’LL BE JUST IN TIME ACTUALLY. SO WE’RE HERE TODAY TO DEMYSTIFY CONGENITAL HEART DISEASE FOR YOU. I HAVE NO DISCLOSURES. I START OFF WITH A QUIZ. EVERYBODY HAS TO PARTICIPATE. WHICH ONE OF THESE YOUNG PEOPLE HAVE A BIRTH KE DEFECT? HOW MANY PEOPLE THINK THE CHILD IN A HAS A BIRTH DEFECT? HOW ABOUT B? OKAY. C? OKAY. WELL, THE ANSWER IS, FOR THOSE WHO DIDN’T RAISE YOUR HANDS, THEY ALL HAVE A BIRTH DEFECT. THE FIRST CHILD HAS DOWN’S SYNDROME, SHE MAY ALSO HAVE HEART DISEASE, ABOUT 50% OF CHILDREN WITH DOWN’S SYNDROME HAVE HEART DISEASE. McKENZIE KLEIN, WHO’S AN AMATEUR GOLFER, HAS COMPLEX CONGENITAL HEART DISEASE, AS DOES SHAUN WHITE, WHO’S AN OLYMPIC GOLD MEDAL SNOWBOARDER. NOW, A LOT OF YOU DIDN’T RAISE YOUR HANDS AND WHY DON’T WE THINK OF THIS AS A BIRTH DEFECT? WELL, THE REASON IS THAT WE THINK OF A BIRTH DEFECT AS SOMETHING WE CAN SEE. SO WE COULD SEE THAT THE FIRST CHILD HAS PERHAPS SOME UNUSUAL FACIAL FEATURES AND OTHER FEATURE, AND THAT MAY BE ASSOCIATED WITH A BIRTH DEFECT. BUT WE DON’T THINK OF HEART DISEASE AS A BIRTH DEFECT. IN FACT, MOST CHILDREN ARE HEALTHY, AND WHEN WE THINK OF A CHILDHOOD DISEASE, WE TYPICALLY THINK OF CHILDREN WITH CANCER, THE LITTLE BALD KID IN THE BASEBALL CAP. CONGENITAL HEART DISEASE IS ABOUT THREE TIMES MORE COMMON IN CHILDREN EVERY YEAR THAN PEDIATRIC CANCER AND PART OF THE PURPOSE OF THIS TALK IS TO INCREASE YOUR AWARENESS BECAUSE EVERY 15 MINUTES, A BABY IS BORN WITH A CONGENITAL HEART DEFECT, SO THIS AFTERNOON THERE WILL BE QUITE A FEW BABIES BORN DURING THIS TALK WHO HAVE A CONGENITAL HEART DEFECT. SO HOW DOES THE HEART FORM? THE HEART IS THE EARLIEST ORGAN TO FORM. IT’S PRETTY MUCH FORMED BY EIGHT OR NINE WEEKS OF GESTATION BEFORE MANY WOMEN REALIZE THEY’RE PREGNANT. SO IT STARTS OUT AS A COUPLE OF GROUPS OF CELLS ON TWO SIDES OF THE EMBRYONIC DISK. IT COALESCES INTO THIS SORT OF DOUBLE HORSESHOE, AND THEN FURTHER COALESCES INTO THIS SYMMETRIC TUBE, AND THAT’S THE LAST TIME THE LEFT SIDE OF THE HEART LOOKS LIKE THE RIGHT SIDE OF THE HEART. OVER TIME THROUGH A COMBINATION OF MOLECULAR SIGNALING, AND MECHANICAL FACTORS AND DIFFERENTIAL CELL GROWTH AND CELL DEATH, IT GOES FROM THIS SORT OF PRIMITIVE FORM OF THE HEART HEERP TO THI HERE TO THIS
FINAL MATU
RE FORM OF THE HEART WITH FOUR CHAMBERS, THERE’S A WALL OR A SEPTUM BETWEEN THE TWO SETS OF CHAMBERS, MAJOR ART REAR
ARTERIES THAT COME OFF OF THE HEART THAT FEED THE LUNGS AND THE BODY. SO THIS GOES RIGHT ABOUT 99% OF THE TIME, WHICH ACTUALLY SORT OF AMAZES ME IF YOU LOOK AT THE SLIDE AND THINK ABOUT WHAT’S GOING ON HERE AND THE SHORT AMOUNT OF TIME IN WHICH IT HAPPENS, AND THE 1% OF THE TIME IT DOESN’T GO RIGHT, WE CALL THAT CONGENITAL HEART DISEASE. CONGENITAL MEANS SOMETHING YOU’RE BORN WITH. SO WHAT’S THE SPECTRUM OF CONGENITAL HEART DISEASE? IT’S NOT JUST ONE THING, IN FACT, EVEN IF YOU’RE A LUMPER AND NOT A SPLIT E IT’S ABOUT 35 DIFFERENT THINGS, VARIOUS TYPES OF CONGENITAL HEART DISEASE THAT CAN RANGE FROM THE FAIRLY SIMPLE SHOWN HERE, SO HERE’S OUR NORMAL HEART, TWO OF THE MOST COMMON THINGS WE SEE ARE DEFECTS IN EITHER THE ATRIAL SEPTUM, BETWEEN THE TWO TOP CHAMBERS OF THE HEART, OR THE VENTRICULAR SEPTUM, BETWEEN THE TWO BOTTOM CHAMBERS OF THE HEART. WHERE A LOT OF THE ATTENTION IS, EVEN THOUGH IT’S MORE RARE, IS IN COMPLEX CONGENITAL HEART DISEASE. THIS IS WHERE MOST OF THE ACTION IS IN PEDIATRIC CARDIOLOGY. SO HERE’S McKENZIE KLEIN AGAIN, OUR GOLFER. SHE WAS BORN WITH SOMETHING CALLED HYPOPLASTIC LEFT HEART SYNDROME. THE LEFT SIDE OF HER HEART DID NOT SHOW UP. IT DIDN’T FORM DURING EMBRYONIC DEVELOPMENT. AND SHE’S PLAYING GOLF NOW AFTER THREE SURGERIES, THE FIRST ONE WHICH WOULD HAVE HAPPENED INTO THE FIRST WEEK OF HER LIFE, AND THEN HERE’S SHAUN WHITE, HE HAS HAD AT THE TROLG OF FALLOT, BLUE BABY CARDIAC DEFECT. I WANT TO YOU REMEMBER THAT BECAUSE WE’RE GOING TO TALK ABOUT IT A LITTLE LATER. HERE HE’S GOT TWO VENTRICLES BUT A GIANT HOLE BETWEEN THE TWO VENTRICLES, AND BECAUSE OF REARRANGEMENTS IN MUSCLE TISSUE UNDERNEATH THE PULMONARY ARTERY, HE’S GOT OBSTRUCTION TO BLOOD FLOW HO SO HE’S NOT GETTING
ENOUGH BLOOD TO THE LUNGS TO GET ENOUGH OXYGEN, SO HE’S BLUE. AND THIS WOULD HAVE REQUIRED EITHER ONE OR TWO PROCEDURES — SURGICAL PROCEDURES IN THE FIRST YEAR OF LIFE. AND I JUST WANT TO TAKE A BRIEF SIDE TRIP IN HISTORY. THIS SLIDE FASCINATES ME. THE STATE MUSEUM OF DETMOLD, GERMANY HAS A LARGE MUMMY COLLECTION, THERE’S THIS ONE SMALL MUMMY HERE, THEY ARE ASSESSING USING MODERN IMAGING TECHNIQUES, SO WHEN THEY SCANNED THIS WITH A CT SCAN, WHAT YOU SEE HERE, THEY FOUND OUT THAT THE LEFT VENTRICLE WAS MISSING IN THIS CHILD. THERE’S THIS LITTLE SLIT HERE WHERE THERE WOULD HAVE BEEN THE RIGHT VENTRICLE, THIS IS THE LEFT VENTRICLE, NORMAL SIZE, THEN IN THE 3D RECONSTRUCTION, YOU CAN SEE THE SAME THING HERE. LEFT VENTRICLE IS TINY, THERE’S THIS LITTLE AORTA HERE, THIS IS WHAT McKENZIE KLEIN HAD. AND SO YOU CAN SEE THAT CONGENITAL HEART DISEASE IS NOT NEW. SO I DIDN’T BRING A PATIENT TODAY, IT’S HARD TO BRING A CHILD ON A SCHOOL DAY, BUT I WOULD LIKE YOU TO MEET JOSHUA ORME. JOSHUA WISHES HE COULD BE HERE TODAY. HE SENDS HIS REGARDS. JOSHUA WAS BORN IN DECEMBER OF 2000. HE WAS A NORMAL WEIGHT, FULL TERM, BORN AFTER AN UNCOMPLICATED C-SECTION, AND AFTER THAT, THINGS GOT REALLY INTERESTING. AT FIRST, THE DOCTORS WERE FOCUSED ON HIS CLEFT LIP AND PALATE AND HIS RIGHT ARM. YOU CAN’T REALLY SEE HERE, HE’S UNDERGONE REPAIR OF THE CLEFT LIP AND PALATE, OUR PLASTIC SURGEON SAID IT WAS THE WORST HE’D EVER SEEN, THIS ITSELF REQUIRED A COUPLE OF SURGERY, AND HE DOESN’T JUST HAVE HIS HAND IN HIS POCKET HERE, HIS RIGHT ARM ENDS HERE. SO AS YOU MIGHT IMAGINE, PEOPLE WERE FAIRLY FOCUSED ON STABILIZING THIS CHILD, AND BY ONE DAY OF AGE, HE WAS NOT FEEDING WELL, HE WAS BREATHING FAST, HE WAS PLACED ON OXYGEN AND HE WAS TRANSFERRED TO CHILDREN’S, WHERE I MET HIM. HE ARRIVED ON MY SERVICE, I SEE PATIENTS AT CHILDREN’S IN ADDITION TO MY ACTIVITIES HERE AT NHLBI. SO HOW DID WE FIND OUT WHAT JOSHUA HAD? THE MAIN WAY WE DO DIAGNOSIS IN CONGENITAL HEART DISEASE IS WITH ECHO CARD YO IMRA FEE. IT USES ULTRASOUND, THERE’S NO IONIZING RADIATION. YOU BRING THE ULTRASOUND MACHINE RIGHT TO THE CHILD’S BEDSIDE, AND WITH THIS LITTLE TRANSDUCER, YOU SCAN THROUGH VARIOUS IMAGING PLANES IN THE HEART. THE THREE-DIMENSIONAL STRUCTURE, YOU’RE TRYING TO RE-CREATE IT WITH TWO DIMENSIONAL IMAGING, AT LEAST IN THIS TECHNIQUE, AND AT THE END OF THE ECHO CARDIOGRAM, WE HAVE A COMPLETE PICTURE OF THE HEART. AND IN JOSHUA’S CASE, I’M SORRY, AND SO THIS WAS 15 OR SO YEARS AGO. TODAY, JOSHUA’S MOTHER’S OBSTETRICIAN WOULD HAVE PROBABLY PICKED UP THAT SOMETHING WAS WRONG WITH THE BABY’S HEART ON AN ULTRASOUND, THEN SHE WOULD HAVE UNDERGONE A FETAL ECHO CARDIOGRAM. SO WE CAN LOOK AT THE FETAL HEART STARTING AS EARLY AS 12 TO 15 WEEKS. AND IN ADDITION, SINCE 2011, THERE’S BEEN A NATIONAL PUSH FOR SCREEBINSCREENING AS PART OF
STANDARD NEWBORN SCREENING, SO THIS IS DONE WITH SENSORS ON ONE HAND AND ONE FOOT THAT MEASURE OXYGENATION IN THE BLOOD AND IF THE OXYGENATION LEVEL IS TOO LOW, WHAT IS THE DIFFERENCE BETWEEN THE UPPER AND LOWER EXTREMITIES, ADDITIONAL TESTING IS WARRANTED. SO WHAT DID JOSHUA HAVE IS A NORMAL HEART, I WANT YOU TO FOCUS ON THIS VALVE WHICH IS THE TRY CUSS BITRICUSPID VALVE. JOSHUA’S ECHO LOOKED SOMETHING LIKE THIS. THIS IS THE LEFT VENTRICLE, AND AS YOU CAN SEE, THERE ARE TWO — TO THIS MITRAL VALVE ON THE LEFT SIDE OF THE HEART BUT THERE’S KIND OF THIS PLATE OF TISSUE HERE. SO WHAT JOSHUA HAD IS KNOWN AS TRICUSPID ATRESIA, WHICH MEANS THAT THE RIGHT VENTRICLE DIDN’T FORM PROPERLY. AND HE’S GOT THIS CENTRAL DEFECT HERE BETWEEN HIS LEFT VENTRICLE AND THIS LITTLE RUDE MEP TRI
RUDIMENTARY CHAMBER, WHERE BLOOD FLOWS TO THE PULMONARY ARTERY, SO THIS IS NOT A GOOD THING. SO HOW DID THIS HAPPEN? SO YOU REMEMBER THE DIAGRAM OF HOW THE HEART FORMED. SOMEWHERE BETWEEN THIS STAGE, WHEN THE ATREE OVEN TRICK LAR VALVES ARE FORMING, THESE ARE THE TRAL AND TRICUSPID VALVES OR THEY WILL BECOME. SOMETHING WENT WRONG HERE AND THE TRICUSPID VALVE DIDN’T FORM PROPERLY AND AS A RESULT, THE SEPTUM THAT SHOULD HAVE FORMED BETWEEN THE LEFT VENTRICLE AND RIGHT VENTRICLE ALSO DIDN’T FORM COMPLETELY AND THE RIGHT VENTRICLE ALSO DIDN’T FORM. SO WE DID NOT GET THE NORMAL HEART ON THIS OCCASION. WHY DOES JOSHUA HAVE CONGENITAL HEART DISEASE? LUCKILY A THIRD OF CONGENITAL HEART DISEASE HAS A GENETIC CAUSE. MOSTLY WE’RE FINDING OUT NOW THESE ARE DE NOVO MUTATIONS ALTHOUGH THERE IS SOME FA NIL YAL CONGENITAL HEART DISEASE. THERE ARE ALSO MA TERM AND PA TERM FACTORS, YET IT’S NOT ALWAYS THE MOTHER’S FAULT, THAT ARE ASSOCIATED WITH AN INCREASED RISK OF CONGENITAL HEART DISEASE. ALSO IF YOU HAD A CHILD BEFORE WITH CONGENITAL HEART DISEASE, YOUR RISK IS UP FROM 1%, WHICH IS SORT OF THE BASELINE, TO MAYBE 5 TO 10% OR EVEN HIGHER DEPENDING ON THE TYPE OF CONGENITAL HEART DISEASE. JOSHUA’S MOTHER WITH HER SUBSEQUENT PREGNANCY WOULD HAVE A FETAL ECHO CARDIOGRAM. TWINS FOR SOME REASON BEING PREGNANT WITH TWINS INCREASES YOUR RISK OF CONGENITAL HEART DISEASE, BUT MOSTLY AND THIS IS THE CASE WITH JOSCHKA, IT’S
JOSHUA, IT’S UNCLEAR. SO THE YEAR JOSHUA WAS BORN, HE JOINED 40,000 OTHER NEWBORNS IN THE UNITED STATES WHO WERE BORN WITH CONGENITAL HEART DISEASE, AND HE WAS ALSO ABOUT ONE OF 10,000 WHO HAD CRITICAL CONGENITAL HEART DISEASE, DEFINED AS A CONDITION, PART OF THE SPECTRUM THAT REQUIRES INTERVENTION EITHER IMMEDIATELY OR SOMETIME WITHIN THE FIRST YEAR OF LIFE. HE’S NOW AMONG ROUGHLY A MILLION CHILDREN LIVING WITH CONGENITAL HEART DISEASE AND IN A COUPLE OF YEARS, WHEN HE TURNS 18, HE’LL JOIN THE MORE THAN 1 MILLION ADULTS WHO HAVE CONGENITAL HEART DISEASE BECAUSE OF IMPROVED SURVIVAL OVER THE YEARS, PEOPLE ARE NOW LIVING WELL INTO ADULTHOOD. TRICUSPID ATRESIA IS AMONG THE RAREST OF THESE RARE CONGENITAL HEART CONDITIONS. IT’S ABOUT 1% OF ALL CONGENITAL HEART DISEASE, AND IT WAS FIRST REPORTED ROUGHLY 200 YEARS AGO. THERE’S A SLIGHT MALE PREPONDERANCE, NO RACIAL OR ETHNIC DIFFERENCES THAT WE KNOW OF. IN GENERAL, ACROSS CONGENITAL HEART DISEASE, THE GENDER AND RACIAL AND ETHNIC VARIABLES VARY BY THE CAN BE BUT OVERALL THERE AREN’T MANY DIFFERENCES. SADLY, OF COURSE, AND UNFORTUNATELY, OUTCOMES TEND TO BE DIFFERENT AND WORSE FOR NON-WHITE CHILDREN, SOMETHING WE ARE WORKING ON. I WOULD ALSO NOTE, I MENTIONED JOSHUA’S OTHER ANOMALIES, ROUGHLY 30% OF CHILDREN WITH CONGENITAL HEART DISEASE ALSO HAVE ADDITIONAL WHAT WE CALL EXTRA CARDIAC ANOMALIES. SO JOSHUA’S TREATMENT WAS LARGELY SURGICAL AND INTERVENTIONAL, AND THIS IS REALLY THE MAINSTAY IN CONGENITAL HEART DISEASE. IT’S A STRUCTURAL PROBLEM, WE NEED A STRUCTURAL SOLUTION OR SOLUTIONS. CHIRP WITCHILDREN WITH HEART
DISEASE CERTAINLY TAKE MEDICATION, BUT THEY’RE NOT THE MAINSTAY OF THERAPY FOR THE MOST PART. SO HE HAD — BY THE TIME HE WENT TO KINDERGARTEN, HE THREE HEART SURGERIES AND THREE CARDIAC CATHETERIZATIONS AND ANOTHER CARDIAC CATHETERIZATION BEFORE HIS 10TH BIRTHDAY. SO FOR THOSE WHO DON’T KNOW THIS, IS A SIMPLE CARTOON OF A CARDIAC CATHETERIZATION USING THE LARGE BLOOD VESSELS THAT ARE NEAR THE SURFACE AND THE GROIN, ONE OR MORE CATHETERS ARE INSERTED UP TO THE HEART WHERE PRESSURE MEASUREMENTS CAN BE TAKEN, MEASURES OF HOW WELL THE HEART IS PERFORM RG TAKEN AND INTERVEPTIONS CAN ALSO BE DONE, BALLOONS CAN BE USED TO OPEN UP BLOCKAGES, OPEN UP NARROWED VALVES, AND DEVICES CAN BE USED TO CLOSE THINGS LIKE THE ATRIAL SEPTAL DEFECT AND VENTRICULAR SEPTAL DEFECTS THAT I MENTIONED TO YOU A LITTLE WHILE AGO. SO THIS IS THE PART OF CONGENITAL HEART DISEASE WE REFER TO AS THE PLUMBING ASPECT. WE RECONNECT ABNORMAL CONNECTIONS, WE RELIEVE BLOCKAGES AND WE CORRECT LEAKS. JOSHUA ALSO NEEDED A PACEMAKER WHEN HE WAS ABOUT 14 YEARS OLD AND MANY CASES THIS CAN BE DONE WITH A CARDIAC CATHETERIZATION, BUT IN HIS CASE, BECAUSE OF HIS HEART, HE’S REQUIRED ANOTHER OPEN HEART SURGERY AND INCISION IN HIS STERNUM, THE FOURTH ONE FOR HIM. NOW, THE WRECK ELECTRICAL PART OELECTRICAL PART OF THEHEART
GOES ALONG WI
TH THE PLUMBING PART OF THE HEART, TINY ELECTRICAL COMMUNICATION BETWEEN CELLS ALONG A SPECIALIZED NETWORK THAT ALLOWS THE HEART TO BEAT, AND JOSHUA’S HEART WAS JUST BEATING TOO SLOWLY FOR HIM. HE WAS FATIGUED WITH EXERCISE AND SO HE HAD A PACEMAKER PUT IN LAST YEAR AND HE’S DOING MUCH BETTER NOW. ALONG WITH THESE SURGERIES, HE’S — HE AND HIS MOM HAVE COME TO SEE ME QUITE A FEW TIMES AND HE’S HAD MULTIPLE SURGERIES FOR HIS CLEFT LIP AND PALATE, AND JUST REMEMBER, HE’S ONLY 15. OKAY. SURGERY NUMBER ONE. JOSHUA’S ACTUAL CARDIAC CATHETERIZATION DIAGRAM. SO THESE WERE DONE AFTER THE SURGERY, IN SOME CASES CARDIAC CATHETERIZATION IS DONE TO HELP PLAN FOR THE SURGERY. SO WHEN HE WAS 13 DAYS OLD, HE A BAND PLACED ON HIS MAIN PULMONARY ARTERY HERE. THAT WAS BECAUSE THIS HOLE WAS SO BIG AND THERE WAS BLOOD BEING PUMPED TO HIS PULMONARY ARTERIES UNDER HIGH PRESSURE FROM THE LEFT VENTRICLE, SO HE WAS GETTING TOO MUCH BLOOD FLOW TO HIS LUNGS AND HAVING TROUBLE BREATHING. NOW I WANT YOU TO FOCUS ON THIS AREA, BECAUSE ON THE NEXT SURGERY, HE HAS THE SUPERIOR VENA CAVA, THE MAIN VEIN THAT DRAINS BLOOD FROM THE HEAD AND NECK CONNECTED DIRECTLY TO THE RIGHT PULMONARY ARTERY. REMEMBER THAT BAND, HE’S GOT A LITTLE KINK HERE NOW SO BEFORE THIS SURGERY AND THE CARDIAC CATHETERIZATION PROCEDURE, A CATHETER WAS ADD VABSE ADVANCED
TO THIS POSITION, A BALLOON WAS BLOWN UP IN THIS LITTLE STENT, LIKE A LITTLE STENT TO KEEP THE ARTERY OPEN WAS PLACED. THAT WAS THE CONNECTION, THAT’S THE CATHETERIZATION, THEN AGAIN I WANT YOU TO FOCUS ON THIS BECAUSE HIS NEXT SURGERY AT AGE 3 1/2 YEARS NOW CONNECTS BOTH THE INTERTEEN YOUR VENA CAVA AND THE SUPERVISOR YOAR VENA CAVA DIRECTLY TO HIS PULMONARY ARTERY. I’M ASSUMING MOST OF US IN THIS ROOM, WE’VE GOT A VENTRICLE OVER HERE THAT’S PUMPING BLOOD TO THE PULMONARY ARTERY. THAT IS NOT THE CASE IN JOSHUA, IT’S NOT THE CASE IN ANY CHILD WHO’S BORN WITH SINGLE VENTRICLE PHYSIOLOGY. WE DON’T YET CREATE A SECOND VENTRICLE. THE BLOOD FLOWS ACROSS THE PULMONARY CIRCULATION THROUGH CHANGES IN INTRATHORACIC PRESSURE DUE TO BREATHING AND OTHER FORCES. SO HOW DO WE GET STARTED WITH CONGENITAL HEART SURGERY? I WAS GLAD THAT DR. ARIAS INTRODUCED THIS. I DID WANT TO JUST SAY ONE THING ABOUT ROBERT GROSS, THE DUCTAL LIGATION IN 1938, HE WAS A RESIDENT THEN, HE’D BEEN PROPOSING DOING THIS, AND HIS CHIEF OF SURGERY WAS OPPOSED SO HE WAITED UNTIL THE CHIEF WENT ON VACATION AND THEN LIGATED THIS DUCT AND GOT — WHEN THE CHIEF CAME BACK BUT IT WAS A GREAT THING TO DO. SO I’M GOING TO TALK NOW ABOUT REALLY THE START OF ALL HEART SURGERY, WHICH STARTED WITH CHILDREN, AND THIS IS A STORY OF POOR PEOPLE AND A DOG. SO THIS IS — THE FIRST PERSON, VIVIAN THOMAS. VIVIAN THOMAS GREW UP IN NASHVILLE, AND HE HAD DECIDED THAT HE WANTED TO GO TO MEDICAL SCHOOL AND WAS ALL SET TO DO THAT IN THE FALL OF 1929, WHEN THE STOCK MARKET CRASHED. THIS TOOK THE BANK AND HIS SAVINGS. HE’D BEEN WORKING TO SUPPORT HIMSELF AS A CARPENTER FOR HIS FATHER, WHO WAS A GENERAL CONTRACTOR. NO ONE WAS BUILDING ANYTHING AFTER THE CRASH, AND SO HIS JOB SEARCH TOOK HIM TO THE LAB OF THIS MAN, ALFRED BLAYLOCK, A SURGEON AT VANDERBILT AT THE TIME. THE TRAUMA RESEARCH GOT HIM NOTICED BY JOHNS HOPKINS AND HE WAS RECRUITED THERE, BUT HE SAID HE WOULD ONLY GO IF HE COULD TAKE VIVIEN THOMAS WITH HIM. IN 1941, BLAYLOCK WENT TO BE THE CHIEF OF SURGERY AT HOPKINS. THERE THEY MET DR. TAUSSIG, PEDIATRIC CARDIOLOGIST WORRYING FOR YEARS ABOUT THE PLIGHT OF THESE BLUE BABIES AND WHAT COULD WE DO ABOUT THEM. WELL, IN THE ANIMAL LAB, AND THIS WAS ANNA, ANNA WAS ONE OF THE DOGS, HER PICTURE HANGS IN THE ROTUNDA AT HOPKINS. IN THE ANIMAL LAB, BLAYLOCK AND THOMAS HAD BEEN WORKING ON A MODEL TO CREATE PULMONARY HYPERTENSION, WHICH INVOLVED LIE GATING AND TURNING DOWN AT THE ARTERY — HELEN AND ALL OF THEM THOUGHT THIS MIGHT BE A WAY TO INCREASE THE PULMONARY BLOOD FLOW FOR THESE BLUE BABIES. SO HERE’S EILEEN, 15 MONTHS OLD, AND SHE WEIGHS 9 POUNDS. HER HEART FAILURE IS SO BAD THAT SHE’S BASICALLY THE WEIGHT OF A NEWBORN AND THEY DECIDED IF WE WERE EVER GOING TO TRY THIS ON ANYBODY — SO LATE IN 1944, BLAYLOCK UNDERTOOK THIS PROCEDURE. NOW, HOPKINS WAS SEGREGATED AT THE TIME AND THERE WAS — AT THE BEGINNING OF THE MORNING ABOUT HAVING VIVIEN THOMAS IN THE ROOM, BUT BLAYLOCK SORT OF JUST CROSSED HIS ARMS AND SAID DOING THIS WITHOUT VIF YEN THOMAS, SO THIS IS VIVIEN THOMAS STANDING BEHIND BLAYLOCK DURING THE WHOLE PROCEDURE. IN FACT, THOMAS WAS THE BETTER SURGEON. THOMAS HAD DONE MORE OF THESE PROCEDURES ON DOGS AND IN FACT HE’D EVEN INVENTED TOOLS LIKE THIS VASCULAR CLAMP THAT COULD BE USED IN SHAW SMALL SIZE
BODIES. TODAY, VIVIEN THOMAS WOULD HAVE BEEN A CARDIAC SURGEON. THIS IS THE PROCEDURE THEY DID, THE CLASSIC BLALOCK THOMAS AND WE SHOULD SAY THOMAS SHUNT, I THINK. THEY TOOK THE RIGHT SUBCLAVIAN ARTERY AND ANAS TA MOSTED TO THE PULMONARY ARTERY AND THIS CREATED AN ADDITIONAL PATH OF BLOOD FLOW. TODAY SHE’S ALIVE AND WELL, THIS IS GORTEX, WE NO LONGER TURN DOWN THE SUBCLAVIAN ARTERY. THIS WAS REALLY A SHOT HEARD ROUND THE WORLD MEDICALLY. EYE LEENEILEEN SAXSON WENT TO
SLEEP A BLUE BABY AND WOKE UP A PINK PIONEER IN CONGENITAL HEART DISEASE. THERE HAD BEEN LITTLE OR NO SURGERY OTHER THAN TRY TO SNATCH AND GRAB AND REPAIR A KNIFE WOUND ON THE BATTLEFIELD OF THE HEART. IT WAS CONSIDERED OFF LIMITS. NOT ANYMORE. THIS IS ONE AREA WHERE PEDIATRICS HAS LED THE WAY. SO MY INSTITUTE, NHLBI, IN 1949, THE FIRST YEAR THAT IT AWARDED GRANTS, AWARDED THE PRINCELY SUM OF 11 THOWP DOLLARS T $11,000 TO
ALFRED BL
ALOCK TO CONSIDER HIS WORK AT HOPKINS. SO WHAT IS NHLBI DOING FOR US TODAY? WE ACCEPT GRANTS FROM INVESTIGATORS AND THERE’S A ROBUST INTRAMURAL PROGRAM DOING RESEARCH RELATED TO CONGENITAL HEART DISEASE, BUT I WANT TO TELL BUT SORT OF THTELL YOU
ABOUT THE MAJO
R PROGRAMS WE HAVE. THIS IS A TRANSRANGE OF MOTIONAL PROGRAM THAT INCLUDES THE CARDIOVASCULAR DEVELOPMENT CONSORTIUM IN WHICH A SET OF ACADEMIC RESEARCHERS ARE TRYING TO UNRAVEL THE MOLECULAR UNDERPINNINGS AND ALSO THE COMPLEX TRANSCRIPTIONAL REGULATORY NETWORKS THAT UNDERLIE THE DEVELOPMENT OF NORMAL AND ABNORMAL HEART. PEDIATRIC — LOOKING AT GENETIC CAUSES AND GENETIC CONTRIBUTIONS TO OUTCOME. THEY’VE RECRUITED IN ABOUT FOUR YEARS MORE THAN 10,000 KIDS WITH CONGENITAL HEART DISEASE AND IN MANY CASES WITH BOTH OF THEIR PARENTS. PEDIATRIC HEART NETWORK IS THE OLDEST MEMBER OF THIS CONSORTIUM CONSORTIUM, I’M GOING TO TALK A LITTLE MORE ABOUT THAT TOAMENT MOAMENTLY, AND TOGETHER THIS IS NHLBI’S BENCH TO BASSINET TRANSLATIONAL PROGRAM. SO HERE’S A PEDIATRIC HEART NETWORK IN 2016, WE’RE 15 YEARS OLD NOW, THERE’S NINE MAIN CLINICAL SITES A WHOLE HOST OF AUXILIARY SITES, AND THE NEW ENGLAND RESEARCH INSTITUTE IN BOSTON. SINCE ITS FOUNDING, THE PEDIATRIC HEART NETWORK HAS CONDUCTED MORE THAN 20 STUDIES AND IS CURRENTLY — HAS SEVERAL ONGOING, INCLUDING A LANDMARK SURGICAL CLINICAL TRIAL THAT INVOLVED 555 INCIDENCE WITH HYPOPLASTIC LEFT HEART SYNDROME IN WHICH THE BLALOCK SHUNT WAS RANDOMLY APAIRED TO A NOVEL APPROACH WITH SINGLE VENT KEL PHYSIOLOGY. THE NOVEL APPROACH WAS ASSOCIATED WITH FEWER DEATHS AND TRANSPLANTS AT THE END OF THE YEAR, WHICH WAS THE TRIAL END POINT. SINCE THEN, HOWEVER, THE DIFFERENCE HAS GONE AWAY AND SO THAT STORY IS STILL BEING TOLD AND THE BLALOCK TAUSSIG SHUNT IS PRETTY MUCH STILL IN THE MIX. LET’S GO BACK TO JOSHUA FOR A MINUTE. JOSHUA WAS BORN AT A GOOD TIME. SO THE RED LINE IS INFANT MORTALITY, CONGENITAL HEART DISEASE INFANT MORTALITY IS THE BLUE LINE AND THE SCALE IS OVER HERE, THAT’S PER THOUSAND LIVE BIRTHS. YOU CAN SEE OVER THE PAST SIX DECADES, THIS HAS COME DOWN BLI AND WHEN JOSHUA WAS BORN HERE IN 2000, THIS WAS A PRETTY GOOD PLACE TO BE BORN. MOST CHILDREN EVEN THOUGH THE COMPLEX CONGENITAL HEART DISEASE SURVIVED INFANCY, SURVIVED CHILDHOOD AND GROW INTO ADULTHOOD THESE DAYS. I WANT TO SAY ONE THING NOW ABOUT THE QUALITY OF THAT SURVIVAL. SO KIDS ARE SURVIVING NOW. BUT IT’S NOT A AN EASY LIFE ALL THE TIME. YOU’VE HEARD ME TALK ABOUT THE NUMBER OF PROCEDURES AND THE AMOUNT OF HEALTHCARE THAT JOSHUA HAS HAD. THINK ABOUT THE IMPACT OF HIS FAMILY AND OTHER SIBLINGS. BUT ALSO MANY CHILDREN WITH CONGENITAL HEART DISEASE HAVE NEURODEVELOPMENTAL DISABILITIES AND LEARNING DISABILITIES. SO THIS IS WORK FROM THE PEDIATRIC CARDIAC GENOMICS CONSORTIUM, WHICH SUGGESTS THAT A NUMBER OF THESE HAVE A GENETIC CAUSE. THERE ARE OTHER POTENTIAL CAUSES, OPEN HEART SURGERY AND CARDIOPULMONARY BYPASS CAUSES THE ACTIVATION OF INFLAMMATORY MEDIATORS, WHICH IS NOT SO GOOD FOR YOUR BRAIN. MANY OF THESE KIDS LIKE JOSHUA ARE CYANOTIC OR BLUE FOR THE FIRST FEW YEARS OF LIFE, THAT’S NOT GOOD FOR YOUR BRAIN. THE ABNORMAL PLUMBING MAY NEED TO ABNORMAL BLOOD FLOW TO THE BRAIN, WHICH ALSO MAY NOT BE GOOD. BUT HERE WE SEE A GENETIC EXPLANATION AS WELL. SO I AM NOT GENETICIST, I’M NOT GOING TO GO INTO THIS IN DETAIL, PLEASE DON’T ASK ME ANY QUESTIONS ABOUT THIS, BUT BASICALLY THESE ARE GENES EXPRESSED IN HEART DEVELOPMENT AND GENES EXPRESSED IN BRAIN VERDEVELOPMENT, AND WHAT WE SEE
IN THE UPPER QUARTILE IS THESE GENES TRAVELING TOGETHER, SUGGESTING THAT THE SAME MUTATIONS THAT ARE ASSOCIATED WITH CONGENITAL HEART DISEASE ARE ALSO ASSOCIATED WITH NEURODEVELOPMENTAL DEFECTS, SO THERE MAY BE A GENETIC UNDERPINNING TO ALL OF THIS. THIS MAY HELP US NOT SO MUCH TREAT CHILDREN BUT IDENTIFY THOSE WHO MIGHT BE AT THE HIGHEST RISK. SO WHAT ABOUT COST? I DON’T KNOW IF THIS IS TO SCALE, BUT IT’S ABOUT 85 TIMES AS MUCH HEART DISEASE IN ADULTS AS IN CHILDREN, AND YET IF YOU LOOK AT THE HOSPITAL COSTS ALONE, NEVER MIND THE SOCIETAL COSTS, THE COST OF EARLY DEATHS, THE OPPORTUNITY COST, COST OF FAMILIES, JUST THE HOSPITAL COSTS, ARE ONLY 12 TIMES AS HIGH FOR ADULT HEART DISEASE AS PEDIATRICS, SO THERE’S A VERY DISPROPORTIONATE COST BURDEN RELATED TO CONGENITAL HEART DISEASE. JOSHUA’S CARE SO FAR, JUST HIS HOSPITAL CARE FOR CARDIOLOGY, NOT HIS LIP, NOT HIS CLEFT PALATE, IS HALF A MILLION DOLLARS, AND AGAIN, HE’S ONLY 15 YEARS OLD. I’M GOING TO SPEND TWO MORE SLIDES ON SOME POTENTIAL FUTURE STRATEGIES. SO STEM CELLS HAVE BEEN USED LARGELY IN CARDIOLOGY, STEM CELLS HAVE BEEN USED PRIMARILY IN ADULTS TO TREATIS TREAT
ISCHEMIC HEART DISEASE, BUT SOME MAY ALSO BE ABLE TO BE USED IN CHISH. CHILDREN. YOU CAN GET STEM CELLS, YOU CAN GET STEM CELLS GENERATED FROM THE FETUS, FROM THE UMBILICAL CORD BLOOD AT BERTH, AND DURING SURGERIES AFTER BIRTH, YOU CAN GET TISSUED FROM THE HEART TO GENERATE STEM CELLS. HERE IN THIS SLIDE, WHAT THEY’RE SHOWING IS USING THOSE STEM CELLS AS WELL AS SOME GRAFT MATERIAL TO PUT SHUNTS AND OTHER THINGS IN CHILDREN WHICH CAN GROW WITH THEM, SO SURGERY IS GREAT, SURGERY IS LIFE SAVING, BUT SYNTHETIC MATERIAL DOESN’T GROW WITH THE CHILD. AND SURGERY CAUSES SCARRING AND ARRHYTHMIAS AND CAN CAUSE CARDIAC DYSFUNCTION OVER TIME, SO IT WOULD BE NICE IF WE COULD COULD PUT SOMETHING IN A CHILD THAT WAS MORE NATURAL, SO TO SPEAK, AND WOULD GROW WITH THEM. BUT ANOTHER POTENTIAL USE OF STEM CELL THERAPY IS IN CHILDREN WITH HYPOPLASTIC LEFT HEART SYNDROME. SO THIS IS REALLY THE FIRST TRIAL OF STEM CELL THERAPY. THIS WAS DELIVERED BY A CORONARY ARTERY CATHETER, INFUSION OF CARDIAC PROGENITOR CELLS. SO CHILDREN WITH HYPOPLASTIC LEFT HEART SYNDROME, SEVEN OF THEM, WHO WERE UNDERGOING THEIR SECOND OR THIRD PHASE OF SURGERY, AT THE TIME OF SURGERY, CELLS WERE HARVESTED FROM CARDIAC TISSUE, THEY WERE GROWN UP AND ABOUT 30 DAYS AFTER THE SURGERY, THEY WERE INFUSED. AND THERE WERE SEVEN CONTROL CHILDREN, SO THE CONTROLS ARE IN BLACK AND THE TREATED CHILDREN ARE IN RED. EJECTION FRACTION IS ONE MEASURE OF HOW WELL THE HEART IS SQUEEZING WITH EVERY HEART BEAT. DURING THE 18 MONTHS IN WHICH THEY WERE FOLLOWED, THERE WAS NO CHANGE, NO IMPROVEMENT IN EJECTION FRACTION, AND THIS EJECTION FRACTION ISN’T SO HOT HERE. IN THE TREATED CHILDREN, HOWEVER, THE EJECTION FRACTION WENT UP SIGNIFICANTLY. THESE P VALUES ALL HAVE A LOT OF ZEROS AFTER THE DECIMAL POINT, WHICH ILLUSTRATES SIGNIFICANCE. AND ANOTHER THING IN CONGENITAL HEART DISEASE, THE KIDS ARE ALWAYS SMALL. AND SO THE CONTROL CHILDREN HERE, THEIR GROWTH DID NOT CHANGE OVER THESE 18 MONTHS. WHICH IS SORT OF SAD IF YOU THINK ABOUT IT. THEY’RE SUPPOSED TO GROW IN 18 MONTHS. THESE ARE KIDS WHO ARE THREE, FOUR, FIVE, SIX YEARS OLD. HOWEVER, THE TREATED CHILDREN DID GROW OVER THIS PEERT. PERIOD OF TIME. SEVEN CHILDREN TREATED DOES NOT TELL US THAT WE CAN CHANGE TO THIS THERAPY, IT’S ALSO A COMPLEX THERAPY BUT THIS IS SOMETHING TO THINK ABOUT FOR THE FUTURE. SO I’D LIKE TO NOW INTRODUCE MY COLLEAGUE WHO WAS CAUGHT IN TRAFFIC. LAURA OL VAIR A OLE VAIR A,
DOING WONDERFUL WORK WITH ADVANCED IMAGING AND 3D PRINTING. SHE HASN’T BROUGHT A PATIENT BUT SHE’S BROUGHT A HEART WITH HER, SO THANK YOU. SHE AND I WILL TAKE QUESTIONS TOGETHER. [APPLAUSE]>>THANK YOU, GAIL, THAT WAS WONDERFUL. YOU MIGHT HAVE SEEN LAURA’S WORK IN THE “WASHINGTON POST” ABOUT A YEAR AND A HALF AGO, WHEN THEY DID A PIECE ON HER AND HER WORK WITH 3D PRINTING OF HEARTS. LAURA WAS ONCE MY FELLOW SO I TAKE FULL CREDIT FOR EVERY SINGLE THING SHE’S ACCOMPLISHED. [LAUGHTER]>>THANK YOU. I APOLOGIZE I WAS A LITTLE LATE, I WAS IMAGING ONE OF OUR CHILDREN DOWN AT CHILDREN’S BEFORE I CAME UP HERE. IT’S REALLY — WHAT I’M ABOUT TO TELL YOU ANYWAY IS THAT THE IMAGING WORK IS — O I’M SORRY. CAN YOU NOT HEAR? IMAGING IS A TEAM SPORT IN THE 3D PRINTING THAT WE DO. THANK YOU VERY MUCH. THANKS FOR THE OPPORTUNITY TO SPEAK TO ALL OF YOU TODAY. I APPRECIATE IT. SO KIND OF REVIEW SOME PROGRESS THAT HAS BEEN MADE BY ALL OF US WHO DO CARDIOVASCULAR IMAGING, BRIEFLY DESCRIBE THE 3D PRINTING WORK FLOW FROM TAKING A PICTURE TO PRINTING OUT A HEART. THERE ARE MANY DEFECTS AND WITHIN EACH DEFECT — — LARGELY ON HOW THE HEART APPEARS ON IMAGING. IMAGING — YOU CAN TAKE THIS WITH A GRAIN OF SALT BUT I THINK IMAGING IS OF PAIR MOUNT IMPORTANCE IN MAKING DECISIONS FOR YOUR PATIENTS. AND IN STUDYING CONGENITAL HEART DISEASE AND TRYING TO IMPROVE OUTCOMES IN OUR OVERALL PATIENT POPULATION. SO WHAT WE HAVE ARE PATIENTS WHO REQUIRE A FAIR AMOUNT OF CARE, AND EACH ASPECT OF THEIR CARE IS A BIT COMPLICATED SO THEY REQUIRE KIND OF EXTENSIVE CARDIAC IMAGING AND OFTEN SPECIAL 3D IMAGING, THEY OFTEN REQUIRE PROCEDURES SO PROCEDURES CAN BE IN THE CARDIAC CATHETERIZATION LAB OR THE OPERATING ROOM, THEY REQUIRE EXPERT INTRAOPERATIVE CARE AS WELL AS POS POSTOPERATIVE ICU
CARE. WHAT THIS ALL BOYLES DOWN TO IS I BELIEVE THEY NEED INDIVIDUALIZED SPECIALIZED CARE. MAYBE WE COULD BACK UP A MOMENT AND TALK A LITTLE BIT MORE ABOUT WHAT GAIL KIND OF EXHIBIT DUED IN HER TALK. THE FOUNDATION OF HOW WE THINK OF CONGENITAL HEART DISEASE, THE WHOLE CLASSIFICATION SYSTEM, IS DERIVED FROM PATHOLOGY SPECIMENS. THIS MAY SEEM OBVIOUS BUT WE NEED TO THINK ABOUT THAT. 60 YEARS AGO, THE CHILDREN WE TREAT EVERY DAY, THEIR HEART DISEASE WAS LETHAL, AND THE WAY PEOPLE DESCRIBED IT AND CAME UP WITH CLASSIFICATIONS BY DOING WHAT IS BEING DONE IN THIS PICTURE DIRECTLY INSPECTING A PATHOLOGY SPECIMEN, LOOKING INSEEDINSIDE, LOOKING AT THE
DIFFERENT FEATURES AND BASICALLY HOLDING A HEART IN YOUR HAND AND FIGURING OUT WHAT WAS WRONG WITH THAT HEART IN A VERY SPECIFIC WAY. I DO JUST WANT TO DRAW EVERYONE’S ATTENTION IF YOU WANT FURTHER READING ON THIS SUBJECT OF CARDIAC DEVELOPMENT, THIS REFERENCE HERE ON THE RIGHT, THE BLACK AND WHITE PHOTO, WAS WORK DONE COLLABORATING WITH INVESTIGATORS I BELIEVE IN THE INTRAMURAL NHLBI, OUTSTANDING PAPER, SHE WAS ABLE TO IMAGE FETUSES BETWEEN 6 AND ABOUT 9 1/2 WEEKS AND WENT THROUGH AND KIND OF CONFIRMED A LOT OF OUR SUSPICIONS O AS A COMMUNITY
ABOUT HEART LOOPING, HEART SEPTATION, I THINK THE ARTICLE IS FASCINATING SO I RECOMMEND IT FOR FURTHER READING. SO WE’LL TALK ABOUT IMAGING. ULTRASOUND. THIS IS OUR MAINSTAY OF IMAGING. ULTRASOUND IS EASY, IT’S CHEAP, THERE’S NO LONG-TERM EFFECTS OF ULTRASOUND, DOESN’T REQUIRE SEDATION OR I.V., HAS EXCELLENT TEMPORAL RESOLUTION, IE, HOW MANY — HOW QUICKLY PICTURES CAN BE REPEATED TO CREATE A MOVIE OF THE CARDIAC CYCLE, EXCELLENT SPATIAL RESOLUTION, WE CAN IMAGE PEOPLE OUR SIZE, ADULTS, AND MY COLLEAGUES IN FETAL MEDICINE CAN USE A SPECIAL PROBE AND IMAGE A FETUS AT 12 WEEKS GESTATION AND DETERMINE IF THEY HAVE — YOU CAN ALSO SEE BLOOD FLOW AS DEPICTED IN THIS MOVIE HERE, WE CAN SEE SEPTAL DEFECTS, WE CAN SEE VALVE LEAK. ECHO IS GREAT BUT FRANKLY CONGENITAL HEART DISEASE OCCURS IN THREE DIMENSIONS AND WE REALLY NEED TO UNDERSTAND RELATIONSHIPS OF EACH OF THE DIFFERENT ASPECTS OF THE FEATURES TO EACH OTHER. SO ENTER MAGNETIC RESONANCE IMAGING. THIS IS A SERIES OF KIND OF A CONTINUOUS SERIES OF — IMAGES DONE DOWN AT CHILDREN’S AT THE BEGINNING OF OUR COMBINED PROJECT, WOR COLLABORATE WITH US
IN ORDER TO ACCOMPLISH. SO CARDIAC MAGNETIC RESONANCE IMAGING IS EXCITING BECAUSE IT’S — THE SPATIAL AND TEMPORAL RESOLUTION, THEY AREN’T WHAT HE COCAN DO BUT THEY CERTAINLY ARE GETTING THERE, AND THE VALUE ADDED HEERYLY IS THAT WE CAN SEE DEFECTS IN THREE DIMENSIONS WITH THE USE OF A LITTLE I.V. CONTRAST, WE CAN GET BEAUTIFUL ANGIOGRAMS WITH ISOTROPIC RESOLUTION, SUCH AS THIS ONE. THIS IS A 4-KILO CHILD THAT WAS DONE IN OUR INSTITUTION, HAS A DOUBLE AORTIC ARCH, THIS CHILD BECAUSE OF THIS ANGI — I WAS
SHOWING THIS TO SOMEONE AT MY INSTITUTION, PETER KIM, WHO HEADS UP OUR INSTITUTE FOR SURGICAL EXCELLENCE, AND HE ASKED ME, DO YOU THINK YOU COULD PRINT THAT? AND I SAID, MAYBE. I DON’T KNOW. SO 3D PRINTING. A LOT OF PEOPLE, CERTAINLY IF YOU READ ANY NEWS, LAY PRESS NEWS OUTLET, YOU’VE SEEN ARTICLES ON 3D PRINTING, 3D PRINTING AND HEALTH, SEEMS LIKE EVERYONE’S INTERESTING I
INTERESTED IN 3D PRINTING. IN 2006, THERE’S BEEN SCIENTIFIC PAPERS USING 3D PRINTING TO DISPLAY HEART DEFECTS. IT’S INTERESTING TO SEE HOW THE MODELS HAVE CHANGED OVER THE YEARS. MY LAB IS VERY FOCUSED ON PRINTING ACTUALLY FROM ECHO, BUT CERTAINLY ANY 3D IMAGING MODALITY CAN THEN BE USED TO MAKE A 3D SEGMENTATION, WHICH CAN BE PRINTED OUT IF NECESSARY. SO THE KIND OF STATE OF WHERE WE ARE RIGHT NOW WITH 3D M MODELING AND PRINTING, THEY’RE MORE AFFORDABLE THAN EVER BEFORE, YOU CAN GO ON AMAZON TONIGHT, ORDER ONE FOR $500 AND HAVE IT SHIPPED TO YOUR HOUSE IN TWO DAYS IF YOU WANT. MOST ALLOW FOR REALLY EASY SEGMENTATION OF VERY COMPLEX SHAPES LINESLIKE THE HEART, AND WE ARE AT KIND OF A REALLY NICE PERIOD OF TIME WHERE WE CAN REALLY DO BEAUTIFUL 3 DIMENSIONAL IMAGING USING MR, CT OR ECHO. OBSTRUCTIONAL HEART DEFECTS, PARTICULARLY BECAUSE THEY IMAGE SO WELL. SO FOR THOSE NOT FAMILIAR, BASICALLY A 3 D-DAY TACET I 3D
DATASET —
FOR INCLUSION AND FOR EXCLUSION AND EVENTUAL DIGITAL MODEL, SO AS YOU IF SLIC DID SLICE GO SLICE
BY SLICE, Y
OU CREATE THIS MODEL OF THE HEART, THAT DIGITAL MODEL CAN BE DEFINED IN POST PROCESSING, THEN PRINTED OUT ON A PRINTER AS DEPICTED IN PANEL 3 DOWN AT THE BOTTOM. SO HOW DO THESE HEART MODELS IMPACT CHILDREN WITH HEART DISEASE? THEY CAN BE USED IN MANAGEMENT DECISION-MAKING, I HAVE A PATIENT WITH HEART DISEASE X, SHOULD I DO SURGERY A, B OR CATHETER — ONCE THE MANAGEMENT DECISION IS BEING MADE, THEY CAN BE USED IN POSTOPERATIVE CARE. SO I HAVE A CASE TO SHOW YOU VERY BRIEFLY, THIS IS A 31-YEAR-OLD MAN WHO CAME WITH CHILDREN’S, THE PULMONARY ARTERY AROSE FROM THE LEFT VENTRICLE AND THE AORTA AROSE FROM THE RIGHT VENTRICLE. HE UNDERWENT REPAIR IN INFANCY THAT WAS POPULAR AT THE TIME, WHERE PULMONARY VENOUS RETURNS OFF THE RED BLOOD BACK TO THE LEFT ATRIUM, LATER REROUTED THROUGH THE TRICUSPID VALVE AND OUT THE AORTA. MITRAL VALVE AND PULMONARY ARTERY TO RE-ESTABLISH CIRCULATION. RATHER THAN IN PAIR THE
PARALLEL, HE HAD A KNOWN COMPLICATION, WHERE BASICALLY THE RED BLOOD COMES IN TO THE BACK OF THE HEART, HAS A TOUGH TIME GETTING OVER TO THE TRY CUSS BID VALVE, AND WE UNDERWENT CARDIAC — TO KIND OF UNDERSTAND HIS ANATOMY, HE HAD A CT BECAUSE HE A PACEMAKER, AND HAD A MODEL PRINTED OUT BASED OFF OF THIS IMAGING DATASET, BLACK ARROWS INDICATE IND
INDICATE THE ARE
A OF STENOSIS, UNDERSTAND WHERE THE SNOW CYST IS, ACTUALLY DO KIND OF A DRY RUN, ANGIOPLASTY, THIS ECHO PICTURE DEPICTS ON THE LEFD SIGH — THIS WAS A PREDONE PICTURE WHERE THERE’S A LOT OF HIGH VELOCITY SIGNAL INDICATING A LOT OF STENOSIS. IN THE LEFT PANEL, AND AFTER THE ACCIDENT PLACEMENT AND RELEASE OF STENOSIS, THE FLOW WITH LOCAL — LAMINAR — HE HAD A SUCCESSFUL PRETOUR. WE HAVE ANOTHER CASE, THE WOMAN WHO ACTUALLY — THIS IS A CASE THAT DR. LEADER MAN WORKED WITH PHYSICIANS TOWN AT — AND THE TEAM DOWN AT CHILDREN’S ON A WOMAN WHO HAD — SHE WASN’T BORN WITH A VENTRICULAR SEPTAL DEFECT BUT UP FORTUNATELY DEVELOPED ONE AS PART OF HER SEVERE — YES? OH, SURE. SURE. YES. I’M HAPPY TO ANSWER QUESTIONS IF ANYONE HAS ONE. SO ANYWAY, THIS WOMAN HAD A VEN VENTRICULAR SEPTAL DEFECT SO A HOLE BETWEEN THE BOTTOM TWO CHAMBERS OF THE HEART THAT WASN’T SUPPOSED TO BE THERE, DEVELOPED AS A RESULT OF HER SEVERE CORONARY ARTERY DISEASE, WHICH IS A KNOWN BUT RARE COMPLICATION. SO SHE HAD A HOLE LEAKING BLOOD FROM THE LEFT TO THE RIGHT VENTRICLE. SHE WENT INTO SEVERE CONGESTIVE HEART FAILURE BECAUSE OF THIS, AND THE HOLE NEEDED TO BE CLOSED, WHICH WASN’T REALLY AN OPERATIVE CANNED TAT CANDIDATE
AND THE HOL
E LOOKED LIKE IT WOULD BE AMENABLE TO CLOSURE IN THE CARDIAC CATHETERIZATION LAB, WHICH DOESN’T INVOLVE SURGERY. SO SHE ALSO HAD A CARDIAC CT FOR PLANNING PURPOSES TO BETTER UNDERSTAND HER INDIVIDUALIZED VERSION OF THE VENTRICULAR SEPTAL DEFECT BECAUSE AGAIN SHE WASN’T BORN WITH THIS, IT DEVELOPED, AND WHEN THINGS DEVELOP BY THIS MANNER, THEY CAN KIND OF DEVELOP RANDOMLY. SO ORANGE ARROWS HERE INDICATE THE DEFECT. THE LEFT PANEL — SORRY, THE RIGHT PANELS AND THEN THE TOP LEFT PANEL ARE THE CT IMAGES AND THEN THE BLUE IS THE SEGMENTATION SO THOSE WERE THE VOXELS SELECTED INTO THE MODEL, THEN THE YELLOW IN THE BOTTOM RIGHT IS THE DIGITAL VERSION OF THE MODEL. I HAVE ONE HERE IF ANYONE WANTS TO SEE AFTER THE TALKS ARE DOB. SO SHE WAS TAKEN TO THE CARDIAC CATHETERIZATION LABORATORY. THIS IS AN ANGIOGRAM SO IN THE LABORATORY, THIS IS A CATHETER THAT’S GONE UP LIKE DOWN HER AORTA, DOWN THROUGH HER AORTA VALVE AND INTO HER LEFT VENTRICLE, INJECTING CONTRAST INTO THE LEFT VENTRICLE, AND DOWN HERE YOU MIGHT BE ABLE TO SEE THERE’S SOME CONTRAST THAT KIND OF LEAKS ACROSS HERE, THIS IS THE WALL, THE INTERVENTRICULAR SEPTUM AND THE HOLE IS DOWN HERE. AND OVER IN THE RIGHT, WE HAVE A SUCCESSFUL PLACEMENT OF THE DEVICE IN THIS WOMAN. SO JUST ANOTHER EXAMPLE OF WHEN YOU HAVE A UNIQUE INDIVIDUAL PROBLEM, I DON’T KNOW THAT A 3D MODEL COMPLETELY MAKES SOMETHING THAT’S UNDOABLE DOABLE, BUT IT CERTAINLY HELPS, I THINK, GUIDE THE PROCESS. SO THE NEXT DIRECTION OUR LAB IS GOING IN, I STARTED THINKING YEAH, WE CAN PRINT THESE HEART MODELS, WE CAN MAKE THEM, PRINT THEM OUT. I DON’T KNOW HOW IMPORTANT IT IS TO PRINT THEM OUT. SO WE ACTUALLY DEVELOPED A TABLETBASED APPLICATION WHERE PEOPLE CAN KIND OF GO AND HAVE THEIR OWN EXPERIENCE WITH THE DINL TALDIGITAL MODEL. SO IT’S A TABLET, CAN YOU GO INSIDE, OUTSIDE, LOOK AROUND, THERE’S THE ABILITY TO LABEL MEASURE, ANYTHING YOU WOULD WANT WANT. WHAT WE’RE DOING WITH THESE IS ACTUALLY WHEN PATIENTS HAVE THEIR CARDIAC SURGERIES AND COME BACK TO OUR CARDIAC ICU POSTOPERATIVELY, WE CREATE LIKE A SPECIALIZED TABLET FOR THAT PATIENT AND PUT IT IN THEIR ROOM. THIS IS ACTUALLY ONE OF THOSE TABLETS IN THE ROOM. THIS IS INSIDE THE PATIENT’S ROOM. THE PATIENT’S CARE TEAM IS KIND OF USING THE TABLET. AND WE JUST PUBLISHED A STUDY A FEW MONTHS AGO SO WE PULLED PHYSICIANS AND TRAINING NURSES, WE’RE A PRETTY BIG TEACHING HOSPITAL, ANCILLARY STAFF, PRETTY MUCH EVERYONE UNIVERSALLY ACROSS THE BOARD FOUND THAT THESE DIGITAL — PATIENT-SPECIFIC DIGITAL SIMULATIONS WERE — ENHANCED THEIR ABILITY TO TAKE CARE OF THE PATIENT AND ENHANCED THEIR ABILITY TO HAND OFF WHAT THEY KNEW ABOUT THE PATIENTS TO THE ONCOMING TEAM WHICH IS, I THINK, VERY INTERESTING. I DIDN’T THINK I’D FIND SO MUCH SUPPORT FOR THAT, WHICH IS INTERESTING. WE ARE TRYING TO ORGANIZE A TRIAL BASICALLY OF THESE MODELS, THESE PLASTIC MODELS ON SURGICAL OUTCOMES IN VERY SPECIFIC TYPES OF CONGENITAL HEART DISEASE, WE HAVE 13 PEDIATRIC SITES COMPRISING MOST OF THE MAJOR SITE IN THE CENTER THAT DO CON CONGENITAL HEART SURGERY. WE’VE RAISED A FAIR AMOUNT OF MONEY AND ARE CONTINUING TO RAISE MONEY TO RUN THIS TRIAL TO SEE WHAT EXACTLY THE IMPACT OF THESE MODELS IS. SO I’D LIKE TO THANK EVERYONE FOR YOUR ATTENTION, SORRY IF I SPOKE FAST. HAPPY TO ANSWER QUESTIONS WHENEVER THAT’S APPROPRIATE. [APPLAUSE]>>THANK YOU BOTH VERY MUCH. WE HAVE TIME FOR A FEW QUESTIONS.>>YOU COMMENTED ABOUT — ELECTRICAL SYSTEM THAT THERE’S SCAR TISSUE AND THE SURGERY IS A LITTLE MESSY. CAN YOU COMMENT ON THE ELECTRICAL COMPLICATIONS THEY’LL FACE FOR THE REMAINDER OF THEIR LIFE?>>THINKING ABOUT THE SINGLE VENTRICLE PATIENTS IN PARTICULAR, BECAUSE OF THE AMOUNT OF SURGERY THEY’VE HAD IN ORE NEAR THE ATRIUM, THE RIGHT ATRIUM IS SORT OF WHERE CONDUCTION STARTS IN THE HEART. THEY TEND TO DEVELOP PROBLEMS WITH REGULATING THE HEARTBEAT AND THEY OFTEN HAVE EITHER HEART RATES THAT ARE TOO SLOW, LIKE JOSHUA DID, OR THEY HAVE ABNORMAL HEART RHYTHMS THAT ARISE IN THE ATRIUM, OR CAN ARISE IN THE VENTRICLE. SO A NUMBER OF PATIENTS WITH CONGENITAL HEART DISEASE HAVE EITHER HEART RATES THAT ARE TOO FAST OR TOO SLOW OR AREN’T GOING IN THE ORDER THAT THEY’RE SUPPOSED TO BE GOING, THE CONDUCTION SYSTEM.>>I WONDER, CHILDREN, FETUSES EXPOSED TO THALIDOMIDE WHO DEVELOPED — LIKE YOUR PATIENT SHOWED UNILATERALLY, TO THEY HAVE CONGENITAL HEART DISEASE?>>I DON’T ACTUALLY KNOW. NOT THAT I’M AWARE OF. THIS SYNDROME THAT JOSHUA HAD IS ACTUALLY — WE KNOW IN GENERAL THE TRANSDESCRIPTION FACTOR THAT’S INVOLVED, PDX1, I THINK, AND THAT IS ASSOCIATED WITH A HEART DEFECT. WE HAVEN’T LOOKED AT THAT IN JOSHUA.>>BUT IS THAT ASSOCIATED WITH A CENTRAL NERVOUS SYSTEM –>>CAN BE.>> — DEFECT? IT CAN BE? ALL RIGHT. YES. [INAUDIBLE QUESTION]>>CAN YOU ACTUALLY CORRECT — CAN YOU DEVELOP DEVICES THAT ARE PATIENT-SPECIFIC, SO IS THERE A BENEFIT TO THAT OR HAS THERE BEEN SHOWN TO BUILD ANY PATIENT-SPECIFIC DEVICES FROM THESE 3D MODELS, OR I GUESS THERE’S ALSO LIKE COMPENSATION AFTER YOU PERFORM SOME OF THESE SURGERIES, THERE MUST BE SOME SORT OF BIOLOGICAL COMPENSATION THAT OCCURS. CAN 3D MODELS POTENTIALLY HELP YOU IN TERMS OF SURGICAL PLANNING SO THAT THOSE COMPENSATIONS CAN SOMEWHAT BE BENEFICIAL OR LESS — YOU SAID LIKE THE DEVELOPMENT OF THAT SHUNT FORMATION, ARE THERE WAYS TO PREVENT THAT WITH PRIOR SURGERIES THAT COULD BE KREECTED VIA 3D MODELING OR SOMETHING LIKE THAT?>>I THINK THAT’S A GREAT QUESTION. SO — [INAUDIBLE] FAIR AMOUNT OF WORK OF STIMULATING IMOH DYNAMICS BASED ON THE SHAPE OF — SO IN A PATIENT-SPECIFIC MANNER BASED OFF OF PATIENT IMAGING OF HOW — KIND OF HOW TO OPTIMIZE EITHER A SURGERY THAT’S NOT WORKED OUT WELL OR EVEN OPTIMIZED SOMEONE GOING INTO A SURGERY THAT EVERYONE KNOWS IS GOING TO BE DIFFICULT AND HE HAS KIND OF A — SPECIFIC AND DIFFICULT CASE CASE — PATIENT-SPECIFIC DEVICES, I THINK — 3D PRINTING IN MEDICINE MEDICINE — TO GIVE BLOD FROM THE RIGHT VENTRICLE OUT TO AN UNUSUAL PATTERN OF PULMONARY ARTERIES, SO MAKING, YOU KNOW, LIKE AN ACELLULAR MATRIX, PRINTING CELLS IN THERE, COMING UP WITH KIND OF THE LONG LINES OF WHAT YOU WERE DOING –>>YOU MENTIONED SURGERY — VENA CAVA TO THE PULMONARY ARTERIES, IT’S HARD FOR ME TO UNDERSTAND HOW IT CAN COME DIRECTLY WITHOUT — THE RIGHT VENTRICLE. THANK YOU.>>BASICALLY THERE’S A TRANSPULMONARY GRADIENT GENERATED BY THE MECHANICAL FACTORS ASSOCIATED WITH BEATING AND TO SOME EXTENT, THE CYCLES OF THE HEART ITSELF. THAT’S ABOUT 8-MILLIMETERS OF MERCURY, THE DIFFERENCE, AND THAT’S ENOUGH TO DRIVE THE BLOOD FLOW ACROSS THE PULMONARY ARTERY VASCULATURE ALLOW THE BLOOD TO PICK UP OXYGEN AND RETURN TO THE LEFT ATRIUM. IT’S NOT A GREAT SOLUTION AS YOU MIGHT MANL. MANY OF THESE KIDS IN ADOLESCENCE BEGIN TO HAVE DECREASED EXERCISE TOLERANCE BECAUSE YOU CAN’T PUMP THE BLOOD THROUGH THE LUNGS FAST ENOUGH TO SUPPORT EXERCISE.>>HAVE ANY OF THE GENES THAT HAVE BEEN ASSOCIATED WITH CONGENITAL HEART DISEASE BEEN KNOCKED OUT IN AMOUNTS OR SOMETHING OR CREATE AN ANIMAL MODEL TO LOOK AT, HAS THAT HAPPENED?>>YES, THERE ARE A NUMBER OF DIFFERENT TYPES OF — BOB ADELSTEIN CREATED ONE ACCIDENTALLY WITH ONE OF YOUR MYOSIN EXPERIMENTS, CREATED AN ANIMAL WITH A DOUBLE OUTLET RIGHT VENT KEL. VENTRICLE, SO YES, THERE HAVE BEEN PEOPLE LOOKING AT ANIMAL MODELS OF CONGENITAL HEART DISEASE.>>SOMETIMES IF YOU’RE LUCKY ENOUGH TO FIND AN ASSOCIATED GENE, IT’S VERY COMMON TO PUT IT BACK IN THE ANIMAL TAKING IT FROM A HUMAN SHOWING YOU GET A SIMILAR KIND OF THING. SOMETIMES CAN YOU DO THAT WITH MICE, WHICH ARE MORE EXPENSIVE, OR EVEN WITH ZEBRAFISH.>>[INAUDIBLE]>>IF WE KNOW THE GENES, WE HAVE A GOOD CHANCE OF UNDERSTANDING WHAT OF MECHANISM IS.>>MOST OF THE MECHANISMS SEEM TO BE RELATED TO TRANSCRIPTION FACTORS THAT DON’T WORK THE WAY THEY’RE SUPPOSED TO, AND MORE RECENTLY SOME OF THE WORK OUT OF THE PEDIATRIC CARDIAC GENOMICS CONSORTIUM HAS SUGGESTED THAT HISTONE-MODIFYING FACTORS ARE HEAVILY INVOLVED.>>OKAY. THANK YOU VERY MUCH AND WE’LL PROBABLY HAVE MORE TIME FOR QUESTIONS AFTERWARDS. SO BOB?>>THANKS FOR HAVING ME. I’M AN ADULT CARDIOLOGIST HERE AT THE INTRAMURAL PROGRAM AT NHLBI SO I’LL BE SWITCHING QUESTIONS AND TALK ABOUT NOT MOLECULAR DEVELOPMENT BUT ABOUT SIMPLE PLUMBING. SIMPLE MECHANICAL TREATMENTS FOR STRUCTURAL HEART DISEASE, WHETHER IT IS CONGENITAL OR ADULTS. A LOT OF THESE TREATMENTS HAVE BEEN PERFORMED USING VERY SIMPLE IMAGE GUIDANCE, JUST SHADOWS CAST BY X-RAY BEAMS, IN THE LAST FEW YEARS WE’VE HAD MORE ADVANCED IMAGING CAPABILITIES, WE’VE BEEN ABLE TO EXPAND THE THERAPEUTIC POSSIBILITIES OF TREATMENT THAT DON’T REQUIRE SURGERY. SO I’M FROM THE INTRAMURAL PROGRAM, AND YOU LIKE THE TITLE, TRANSMURAL? THESE THERAPIES UNDER IMAGING GUIDANCE WILL BE CROSSING WALLS. SO LET’S SEE IF YOU THINK THAT’S CUTE. THE WORK IN MY LAB HAS — I’VE BEEN FORTUNATE TO WORK WITH A BUNCH OF RELAY TALENTED CLINICAL AND TECHNICAL PEOPLE HERE AND ABROAD AND AT LOTS OF DIFFERENT MEDICAL CENTERS. TOO NUMEROUS TO COUNT. SO LET’S IMIN B BEGIN BY TALKING CATHETER VERSUS SURGICAL TREATMENT. CATHETER TREATMENT OF A DEVASTATING ILLNESS, WHERE A CORONARY ARTERY IS SUDDENLY BLOCKED. USING VERY SIMPLE — IF YOU GET THERE IN TIME, YOU CAN BLOW OPEN THE HOLE, BLOW OPEN THE BLOCKAGE, RESTORE NORMAL BLOOD FLOW TO THE HEART IF YOU GET THERE IN TIME. THIS IS PRETTY EFFECTIVE AND OCCASIONALLY LIFE SAVING. BY COMPARISON, ANOTHER SIMILAR MECHANICAL THERAPY IS CORONARY BYPASS SURGERY. THIS IS THE VIEW UNDER A ZOOM LENS OF A CAMERA INSIDE THE CHEST, IT’S A ROBOT SUTURING ONE BLOOD VESSEL TO ANOTHER. BY COMPARISON, THE CATHETER-BASED TREATMENT USES A TINY HOLE. THE TARGETS THAT ARE CONSTRAINED BY ANATOMY ARE PRETTY MUCH SHOVING A TUBE INTO ANOTHER TUBE OR ANOTHER CHAMBER, WHEREAS SURGEONS PUT A BIG HOLE IN THE CHEST, THEIR TREATMENTS ARE GUIDED BY — AND THERE’S PRETTY MUCH NO LIMIT TO HOW MUCH INJURY A SURGEON CAN EXPOSE THEIR PATIENT TO IN THE COURSE OF SURGICAL REPAIR. IT’S AN IMPORTANT DIFFERENCE, HERE’S ANOTHER COMPARISON, SURGERY IS MORE LIKE GENERAL CONTRACTING. SO THE TREATMENTS — THE TOOLS ARE MORE SIMPLE AND LESS INVASIVE, THEREFORE LESS INK JEUR JUST, BUT BY COMPARISON, THEY ALSO MAY BE LESS EFFECTIVE. HERE’S A GOOD COMPARISON IF YOU WANT TO DO SOME PLUMBING WORK, YOU PUT A SNAKE IN, THAT MAY NOT BE SO GOOD, A MORE DEFINITIVE REPAIR IS TO BLOW DOWN THE WALL IN YOUR BATHROOM, KNOCK DOWN THE PIPES AND REPLACE THEM. AS A GENERAL RULE, SURGICAL THERAPIES CAN BE MORE EFFECTIVE BUT AT BIGGER EXPENSE OF PATIENT INJURY. SO LET ME GIVE YOU SOME EXAMPLES OF CONGENITAL HEART DISEASE. CATHETER-BASED NON-SURGICAL REPAIRS. THESE ARE ALL GIVEN TO ME BY ELENA GRANT, WHO TRAINED WITH GAIL AND LAURA AND FORTUNATELY WILL BE ROMAN CATHOLIC CHURCHING FROM EMORY UNIVERSITY NEXT YEAR TO BECOME A GROWN-UP HERSELF. THIS IS A CHILD WHO HAS CONSISTENTLY PATENT DUCTUS ARTERIOSUS, WHERE THE LUNGS ARE BYPASSED IN UTERO. THIS CHILD FOR SOME REASON, — HAS FAIL TODAY CLOSE AND THE CHILD HAS OVERCIRCULATION AS A RESULT, AS THE NORMAL PULMONARY RESISTANCE DECLIEPED IN THE EARLY POSTNATAL PERIOD. SO ELENA PUT IN A COMMERCIAL DEVICE, A SELF-EXPANDING SPRING THAT IS SO GROOVY, IT CAN FIT THROUGH THIS TINY TUBE AND BE DEPLOYED ACROSS THE HOLE AND THEN BLOCK OFF THAT PERSISTENTLY PATENT DUCTUS ARTERIOCYST. THIS RECAPITULATES SURGERY FROM 1940, IT TAKES ABOUT 10 MINUTES AND IS NOT TOO INK JEU INJURIOUS
MOST OF THE TIME AND IN THIS CASE PRETTY EFFECTIVE. HERE’S ANOTHER EXAMPLE OF NON-SURGICAL TREATMENT AGAIN COURTESY OF ELENA GRANT. THIS IS A CHILD WHO HAS PULMONARY VALVE THAT IS MALDEVELOPPED AND PRACTICALLY NOT PRESENT. WE CAN SEE THE REMNANT PULMONARY VALVE, SO BLOOD FLOW ISN’T ABLE TO CONNECT THE RIGHT VENTRICLE TO THE PULMONARY CIRCULATION THAT THIS CHILD IS RELYING ON PERSISTENT FETAL CIRCULATION. JUST BY POKING ON A LITTLE GUIDEWIRE THROUGH WHERE THE BLOOD SHOULD BE FLOWING, DR. GRANT WAS ABLE TO ADVANCE A BALLOON, AGAIN TO A TINY, TINY HOLE, IN THIS CASE THROUGH A NECK VEIN. AND RESTORED SOME RUDIMENTARY VALVE FUNCTION BUT, MORE IMPORTANT, RESTORED ANTEGRADE FLOW. SO NOT A PERFECT SOLUTION BUT PRETTY DARN GOOD IN A VERY SIMPLE NON-INJURIOUS PROCEDURE USING RUDIMENTARY IMAGING GUIDANCE, X-RAY IS THAT DOUGH
SHADOWS THAT
YOU SEE. THIS IS A CHILD WHO HAD A AT TETRALOGY OF FALLOT, THE PULMONARY VALVE IS NON-FUNCTIONAL SO BLOOD IS FREELY FLOWING AND THAT WASTES A LOT OF THE ENERGY OF THE RIGHT VENTRICLE AND USING A SIMPLE TRANSCATHETER IMPLANTATION OF A SIMPLE $20,000 DEVICE GIVE OR TAKE, THIS STENTED VALVE IS ABLE TO RESTORE VALVE FUNCTION IN A NON-SURGICAL PRECURE. PROCEDURE. FINALLY, YOU MAY HAVE HEARD OF ANOTHER REVOLUTION IN ADULT STRUCTURAL HEART DISEASE THAT’S IN THE TREATMENT OF AORTIC VALVE STENOSIS. GENERATE AND FAILS TO OPEN. IT’S NOT OPENING OPEN SURGICAL PROCEDURE WHERE THE CHEST IS OPEN, THE HEART — THAT WORKS GREAT IF THEY’RE YOUNG, IT TURNS OUT THIS DISEASE IS MORE OFTEN MANIFEST AMONG THE OLD AND FRAIL. TOLERATES SURGERY WITHOUT COMPLICATIONS. THIS COMMERCIAL — $35,000 DISPOSABLE DEVICE IS IMPLANTED IN A CATHETER PROCEDURE AND RESTORES NORMAL VALVE FUNCTION. FORM AGAIN — SO TO SUMMARIZE, CONTEMPORARY TREATMENTS, WE CAN’T SEE MUCH, WE CAN ACCOMPLISH QUITE A BIT AS LONG AS WE STAY CONFINED WITHIN NORMAL VASCULAR SPACES. WOULDN’T IT BE NICE IF WE COULD SEE WHAT WE’RE DOING. SO I STAND ON THE SHOULDER OF — MOST OF YOU THINK OF MRI AS A FAIRLY LOW LEVEL RESOLUTION TBROO VEE NOISY EXTENSIVE IMAGING MODALITY. TURNS OUT YOU CAN BUY AN X-RAY LAB AND SIT IT NEXT TO YOUR MRI LAB AND TRANSPORT PATIENTS LIKE THE ONE WE TREATED TODAY, — VERY SOPHISTICATED IMAGE ACQUISITION RECONSTRUCTION TECHNIQUES TO GET USEFUL INFORMATION ABOUT HOW THE HEART BEATS, ABOUT HOW MUCH BLOOD FLOWS AND ABOUT THE TISSUE COMPOSITION OF THE HEART TISSUE ITSELF TO GUIDE CA
CATHETERIZATION BECAUSE WE CAN MEASURE BLOOD FLOW VERY ACCURATELY, AVOID RADIATION ALL TOGETHER, AND WE CAN TAKE ADVANTAGE OF MANY DIFFERENT IMAGING CONTRASTS. SO WE STARTED DOING THIS ABOUT TWO OR THREE YEARS AGO, THIS IS OUR FIRST MRI CATHETERIZATION, WE FILLED A BALLOON CATHETER WITH AN MRI CONTRAST AGENT SO IT SHOWS UP WHITE LIKE THIS. WE’RE STEERING FROM ONE CHAMBER TO ANOTHER FROM THE FEMORAL VEIN INTO THE GROIN, UP THROUGH THE SUPERIOR VEN VEE NA CAVA, FROM THE RIGHT VENTRICLE TO THE PULMONARY ARTERY. WE’RE REALLY SPINNING A NOODLE THAT’S ATTACHED TO A BALLOON AND TRYING TO GET IT TO GO TO THE RIGHT PLACE. HERE WE’RE ABLE TO SELECT ONE OR THE OTHER PULMONARY ARTERIES. BECAUSE AVOIDING RADIATION IS PERHAPS LESS IMPORTANT IN THE ADULTS THAT I TREAT, NHLBI INSTALLED AN INTRAMURAL MRI CATH LAB AT LAURA OLIVEIRI’S PLACE AT CHILDREN’S DOWNTOWN. IT’S VERY PRETTY LIKE THIS, OTHERWISE SIMILAR, AND SOME OF THESE PROCEDURES WERE DEVELOPED — WERE INTRODUCED INTO CLINICAL PRACTICE BY — WHO HAS SINCE LEFT US TO MOVE TO SAN DIEGO AND DR. ELENA GRANT, WHOSE IMAGES I SHOWED YOU BEFORE. THEY DO SOME REALLY NICE MOVE OOND’ STILL FRAMES OF THE SAME KIND OF CATHETER TECHNIQUES AS THAT FROM ONE CHAMBER TO ANOTHER, ALL ENTIRELY WITHOUT RADIATION. THAT’S PRETTY HANDY AND IT’S NOW BEEN APPLIED IN ALMOST THREE DOZEN PATIENTS. THAT’S PRETTY NICE. AND WHILE WE’RE IN THE NEIGHBORHOOD, WE CAN MAKE SOME REALLY GROOVY MEASUREMENTS. IF THERE’S A HEART DEFECT, WE CAN ACTUALLY SEE IT WHILE WE’RE SAMPLING BLOOD FLOW IN THE HEART. IF THE PATIENT HAS A COMMON UNRECOGNIZED DISEASE OF ADULTHOOD, IN JUST ABOUT 30 TO 60 SECONDS WITH A MILLILITER OF MRI CONTRAST AGENT, WE CAN MAKE A MAP OF BLOOD FLOW IN THE LUNGS WHILE WE’RE IN THE NEIGHBORHOOD AND GET A LOT OF INFORMATION ABOUT THE PATIENT TO MAKE AN IMPORTANT DIAGNOSIS. SO THAT’S SOME CLINICAL WORK LE. ME SHOW YOU SOME STUFF THAT WE’RE STILL BUSY TRYING TO TRANSLATE FROM ANIMALS INTO PATIENTS. WHAT CAN WE DO? ONE IS A BIOPSY. IIT’S COMMON TO WANT TO DO WHAT REAL SCIENTISTS HAVE DONE IN OTHER DISCIPLINES FOR DECADES IN ONCOLOGY, IN BLOOD DISEASES AND INFECTIONS, IT’S VERY NICE TO BE ABLE TO SAMPLE THE DISEASED TISSUE. IN THE HEART, THAT’S A LITTLE MORE DIFFICULT AND INVASIVE. IT’S INTERESTING TO SEE THE MAKING OF THIS SAUSAGE THAT WE CALL CARDIOLOGY. IN PATIENTS WHO HAVE INFLAMMATORY DISEASE OR FOR EXAMPLE NEED SURVEILLANCE OF A RECENT HEART TRANSPLANT, WE PUT THIS JAW THROUGH THE LEG OR THE NECK INTO THE HEART UNDER X-RAY. CAN YOU TELL WHERE WE ARE IN THE HEART? SO I HAVE A LOT OF — THAT HAVE DONE MAYBE A THOUSAND, I CAN’T REALLY TELL EITHER. I KNOW I’M KIND OF IN THE RIGHT PLACE. I’M SORRY, THIS IS REALLY WHAT WE DO. WE PRETTY MUCH PUT THE FORCEPS IN THE HEART, WE PUT A LITTLE PRESSURE, WE SPIN COUNTERCLOCKWISE, THEN WE CLOSE OUR ICE AND HOP EYES AND HOPE
FOR THE BEST
. BUT WOULDN’T IT BE NICE IF WE COULD SEE WHAT WE WERE SAMPLING? THIS IS WORK THAT’S BEEN REJECTED BY SOME OF THE PEST
BEST CARDIOLOGY JOURNALS. THIS DOESN’T DESTROY THE IMAGE, HE LABELED TISSUE WITH JUST SOME FLUORESCENT MICRO SPHERES AND COMPARING MRI BIOPSY LIKE YOU SEE HERE, WHERE WE CAN SEE THE TARGET, WHERE WE’RE SPINNING OUR CATHETER, THE DIAGNOSTIC YIELD OF MRI — WERE SUPERIOR TO X-RAYS. THAT’S PRETTY GROOVY. IN FACT NHLBI IS INTERESTED TO INTRODUCE THIS INTO CLINICAL PRACTICE FOR PEDIATRICS SO WE’RE WORKING HARD TO BRING THIS TO CLINICAL USE. BUT IT’S A PRETTY BIG AND EXPENSIVE UNDERTAKING. I KNOW YOU’VE SHOWN SOME EXAMPLES OF A CAVOPULMONARY SHUNT — WORKED FOR SOME TIME TO ACCOMPLISH THIS WITHOUT SURGERY. THIS IS PART OF THE STAGED SURGICAL REPAIR AND THE CONNECTION THAT WE’RE TRYING TO MAKE IS BETWEEN THE SUPERIOR VENA CAVA AND THE NEARBY RIGHT PULMONARY ARTERY. CAN EVERYONE MAKE OUT THAT ANATOMY? I KNOW THAT DOESN’T SOUND LIKE A BIG DEAL BUT THERE ARE CRITICAL STRICTURES BETWEEN THE TWO. HERE’S A PIG, AND HERE’S ONE STRUCTURE — THE AORTA. STICKING A NEEDLE FROM THE SUPERIOR VENA CAVA INTO THE PULMONARY ARTERY, ESTABLISHING CONTINUITY BETWEEN THE TWO, USING A SPECIALLY DESIGNED ENDOGRAPH THAT DOESN’T REQUIRE SURGERY TO CONNECT TWO DIFFERENT BLOOD VESSELS AND ACCOMPLISHING THIS CAVOPULMONARY SHUNT IN THIS NICE ARTIFICIALLY COLORED FOLLOW-UP PICTURE. IT WORKS PRETTY DARN WELL, IN FACT, SO NICE THAT WE’RE GOING TO TRY TO USE THIS TO REDUCE THE NUMBER OF MAJOR CARDIOPULMONARY PROCEDURES IN CHILDREN. THERE WAS A QUESTION EARLIER ABOUT RHYTHM DISORDERS AND CONGENITAL HEART DISEASE. ADULT CARDIOLOGISTS ARE REALLY — I REALLY AM DIFFERENTIATED INTO PLUMBING, NOT ELECTRICITY, BUT THAT NEVER STOPPED ME FROM HAVING AN OPINION, SO WE’VE STARTED TO SEE THAT THERE MIGHT BE SOME OPPORTUNITIES TO USE THIS GREAT IMAGING TOOL, MRI, TO GUIDE TREATMENT OF AN ELECTRICAL DISORDER. SO THIS IS AN EXAMPLE OF CONTEMPORARY TREATMENT OF ELECTRICAL DISORDERS, MORE COMMONLY IN ADULTS THAN CHILDREN BUT ADULTS SOMETIMES HAVE — RHYTHM OF THE ATRIA THAT MAY ORIGINATE FROM SOME PLACE, LIKE THE PULMONARY VEIN. SO USING VERY FANCY AND EXPENSIVE TOOLS, ELECTRICIANS PUT CATHETERS IN DIFFERENT PARTS OF THE HEART, AND THEN USE AN ELECTROSURGERY PENCIL, THEY ESSENTIALLY BURN THE HEART MUSCLE AND THEY TRY TO ACCOMPLISH A LINE OF ELECTRICAL DISCONTINUITY. THEY’RE TRYING TO ELECTRICALLY DISCONNECT WHOLE SECTIONS OF THE HEART FROM ANOTHER. THE PROBLEM IS THAT THEY’RE BURNING HEART MUSCLE. THEY CAN’T REALLY SEE THE MUSCLE THAT THEY BURN. THEY JUST KEEP TESTING MULTICHANNEL ELECTRIC ENDS LIKE THIS BEFORE AND AFTER BURNING, AND THEN THEY SEE IF THERE’S EVIDENCE OF ELECTRICAL CONNECTION AND SINCE THEY CAN’T SEE WHAT THEY BURNED, THEY BURN SOME MORE. THEN AFTER THAT, THEY SEE THEY’RE NOT YET SUCCESSFUL SO THEY BURN SOME MORE. THESE ARE VERY SMART, HIGHLY TRAINED PEOPLE. THE DISEASES THAT THEY’RE TREATED CAN BE QUITE DISABLING, SOMETIMES EVEN LIFE-THREATENING, BUT THEY ARE JUST PARALYZED BY NOT HAVING GOOD IMAGING TOOLS. SO WE THOUGHT WE WOULD — I’M SORRY, LET ME SHOW YOU A GOOD EXAMPLE OF WHAT THEY DO. THIS IS A COMO THE PROBLEM,
RADIO FREQUENCY ABLATION IS THE MAIN TOOL, INJURY TO THE HEART THAT’S PROBABLY REVERSIBLE, IT’S LIKE GETTING A BLISTER THAT MAY HEAL. IN THE WEEKS OR MONTHS AFTERWARDS, AS THE INJURY HEALS, THE RHYTHM ABNORMALITY MAY COME BACK. SO THIS WAS SOME WORK WE DID JUST IN ANIMALS. WE FIGURED WHY DON’T WE WATCH AS WE DESTROY HEART TISSUE. INSTEAD OF USING RADIO FREQUENCY ENERGY, WHY DON’T WE USE SOME — TO BE ABLE TO MIX AN MRI IMAGING AGENT — DR. JONATHAN HILL USED TO CALL PROHIBITIVELY EXPENSIVE BUT PRETTY EFFECTIVE. YOU CAN SEE THE DISTRIBUTION OF EACH PIECE OF HEART MUSCLE THAT YOU’RE BURNING AND YOU CAN ESTABLISH KOP CONTINUITY — WE LEARNED WE CAN MAKE BEAUTIFUL — WITH VINEGAR AS OPPOSED TO — AND WE’RE ABLE TO MAKE A MODEL SIMULATING A LIFE-THREATENING RHYTHM DISORDER AND ABLATING THE SO CALLED CRITICA CRITICAL
ISHMUS. SO STAY TUNED, I THINK THIS REALLY HAS POTENTIAL TO MAKE AN IMPACT. SO I DON’T WANT TO SPEND TOO MUCH TIME BUT I WANT TO SHOW YOU ONE OR TWO REALLY GOOD PROCEDURES. I SHOWED YOU SOME POTENTIAL THERAPEUTIC OPPORTUNITIES USING IMAGING GUIDANCE USING MRI, BUT LET ME SHOW YOU SOME STUFF WE’VE DONE USING PLAIN OLD X-RAY. ONE THING I’M REALLY PROUD OF IS SOMETHING THAT WE CALL TRANSCAVAL ACCESS. I SHOWED YOU EARLIER WHEREIN THROUGH THE FEMORAL ARTERY, WE PUT A GIGANTIC APPLIANCE UP INTO THE HEART AND THAT’S REALLY GREAT AND GROOVE EE. GROOVY. THE PROBLEM IS THAT A LARGE MINORITY OF PATIENTS, USUALLY SMALLER WOMEN OR PEOPLE WITH DISEASED ARTERIES AREN’T ELIGIBLE FOR NON-SURGICAL VALVE REPLACEMENT. SO WE THOUGHT WHY DON’T WE TRY SOMETHING A LITTLE DIFFERENT? WE NOTICED THERE ARE PATIENTS WHO HAVE A RUPTURE IN THE ARTERY IN THEIR LEG THAT’S NOT FATAL. IT CAUSES A LITTLE BLEEDING. IT CAN BE REALLY BAD. BUT WHEN THAT RUPTURE SPONTANEOUSLY BLEEDS INTO THE VEIN, MOST PATIENTS TOLERATE THE BLEEDING JUST FINE. WE THOUGHT WE WOULD SIMULATE THAT VERY SAME PROBLEM BY POKING A HOLE FROM THE VEIN, A VERY NICE COMPLIEP COMPLIANT VESSEL,
INTO THE ADJOINING ARTERY. WE CALL THAT TRANSCAVAL ACCESS. IT WAS REALLY REJECTED AS COUNTERINTUITIVE AND RIDICULOUS AND CRAZY AND DANGEROUS. BUT IT’S BEEN NOW USED AT 180 PATIENTS IN OVER 200 CENTERS. LET ME SHOW YOU A LITTLE OF HOW IT WORKS. WE USE SIMPLE CATHETER TOOLS AND SPRAY GUIDANCE TO PUX-RAY
GUIDANCE TO PUT
A HOLE IN THE AORTA, AFTERWARDS WE CLOSE IT USING A TOOL DESIGNED TO CLOSE A HOLE IN THE HEART I SHOWED YOU EARLIER. IT’S LONG BEEN THOUGHT THAT IF YOU MAKE A HOLE IN THE AORTA, THAT THE PATIENT IS GOING TO DIE, IS GOING TO BLEED TO DEATH IN ABOUT A SECOND. WE BELIEVE THAT BECAUSE A LOT OF SURGICAL TRAINEES OVER THE YEARS HAVE TAKEN CARE OF PATIENTS SUFFERING HORRENDOUS TRAUMA, AND IN THAT TRAUMA, THE SURGEON HAS EXPOSED THE RETROPERITONEAL SPACE, THE SPACE BEHIND THE GUT THAT CONTAINS LARGE VESSELS IN THE SPINE. IN ALL THOSE PATIENTS, WHEN THERE WAS A HOLE — WHAT’S INTERESTING IS THAT IF YOU’RE NOT DOING SURGERY, THE RETROPERITONEAL SPACE — AS LONG AS THERE’S A MATCHING HOLE IN THE VEIN, OPPOSITE THE AORTA, THERE IS A PHENOMENON THE VENOUS DECOMPRESSION, SO THE — CAN BE TOLERATED. LET ME GIVE YOU AN EXAMPLE. THIS IS A — THIS PATIENT HAD THIS PROCEDURE AT A HOSPITAL IN DETROIT WHERE I’VE BEEN WORKING TO BRING THIS INTO CLINICAL PRACTICE. THIS IS A PATIENT WHO NEEDED — LEG ARTERIES WERE SIMPLY TOO SMALL. SO WE USE A TECHNIQUE THAT I MENTIONED TO PUT A TUBE FROM THE VEIN INTO THE AORTA, THEN THE TRANSCATHETER VALVE REPLACEMENT WENT FINE. A TRAINEE WAS BEING TAUGHT HOW TO PUT THE CLOSURE DEVICE IN, AND WE CAUTIONED HIM, THAT’S GOOD, DON’T PULL ANY HARDER, DON’T PULL ANY HARDER. BUT HE PULLED SO HARD THE CLOSURE DEVICE WAS PULLED ALL THE WAY OUT. SO NOW WE HAD AN UNCONSTRAINED HOLE BETWEEN THE AORTA THROUGH THE OPEN — THROUGH THE RETROPERITONEAL SPACE AND HERE YOU SEE IT. BUT WITHOUT TOO MUCH DIFFICULT, WE WERE ABLE TO RECROSS AND CLOSE THAT AND THE PATIENT DID FINE, ALTHOUGH AS YOU CAN SEE, THERE WAS A RESIDUAL SMALL AR TIER YOUR VENOUS FISTULA. THERE’S A VIDEO SHOWING
COMPLETE HEALING ONE MONTH LATER. THIS IS BEING APPLIED NOW TO PUT IN TEMPORARY HEART PUMPS, GIGANTIC DEVICE THAT CAN’T BE INTRODUCED INTO THE BODY WITHOUT SURGERY AND WE’VE BEEN ABLE TO TAKE ADVANTAGE OF THIS TECHNIQUE. SO I HAVE A BUNCH OF OTHER X-RAY PROCEDURES BUT I CAN SEE IT’S GETTING DARK OUTSIDE. ARE THERE QUESTIONS YOU’D LIKE ANSWERED INSTEAD? YES. LET’S BRING YOU A MICROPHONE.>>SO DO THOSE FISTULAS EVENTUALLY CLOSE UP OR HEAL IN SOME WAY SO THEY’RE NOT SQUIRTING BLOOD IN SMALL QUANTITIES?>>SO IN THIS CASE, THESE PHYSICIAN-CREATED FISTULAS THAT AREN’T REALLY GOOD FOR YOU, THEY DO CLOSE UP WHEN WE SURVEY THEM. THEY TURN OUT NOT TO BE — TO OUR SURPRISE, THEY TURN OUT TO BE NOT THAT MEDICALLY IMPORTANT, BUT WE HAVE SOME EXPERIENCE FROM OTHER DISEASES, PATIENTS WITH CHRONIC KIDNEY DISEASE ALSO HAVE A FISTULA CREATED IN THEIR ARM TO SERVE AS AN ACCESS SITE FOR HEMHEMODIALYSIS, AND THOSE TEND
TO BE VERY WELL TOLERATED. RESPECTIVE OF LEFT AND RIGHT SERK LAITIONS, THESE PATIENTS SEEM TO TOLERATE IT JUST FINE AND IN AN AUTOPSY EXPERIENCE, IF WE LOOK AT THE SPACE BETWEEN THE AORTA AND CAVA, IT’S GENERALLY NOTHING. IT’S PRETTY AMAZING THAT EVEN PATIENTS WHO ARE 80, NINE AT THE YEAR90 YEARSOLD ARE SO
RESILIENT, THEY’RE ABLE TO TOLERATE THIS INJURY, WHICH IS NOT AS BAD AS — OKAY.>>DO YOU SEE ANY CHANGES IN LIMB PERFUSION WHEN YOU INTRODUCE THESE SHUNTS AT THE BEGINNING OF THE PROCEDURE? I’M ASSUMING SOME PEOPLE MIGHT HAVE LIKE PERIPHERAL ARTERY DISEASE IN THE LOWER LIMBS OR SOMETHING LIKE THAT THAT MAY BE — BY A SHUNT? IS THAT SOMETHING THAT’S BEEN LOOKED AT?>>SO THE QUESTION IS DO WE CAUSE LIMB ISCHEMIA BY WORKING ON PEOPLE, OR MAL MALPERFUSION SYNDROMES? FOR MANY ADVANCED PROCEDURES BEING OFFERED TO PATIENTS, FOR EXAMPLE, WITH CARDIOGENIC SHOCK, THEY MAY HAVE A TEMPORARY HEART PUMP PUT IN OR TEMPORARY PULMONARY SYSTEM PUT IN, THEY IP DIED MAY SUFFER LIMB ISCHEMIA, THEY MAY SURVIVE BUT MAY NOT BE ABLE TO WALK OUT OF THE HOSPITAL BECAUSE THEY’LL HAVE LITERALLY LIMB LOSS RELATED TO THE DEVICES. SO INDEED USING THIS KIND OF TRANSCAVAL APPROACH IS ONE WAY TO AVOID LIMB ISCHEMIA. BUT IT’S ALSO INTERESTING THAT PATIENTS TEND TO BE VERY RESILIENT. CAN YOU DO AN AWFUL LOT TO THEM, YOU CAN INTERRUPT PERFUSION TO A LIMB OR A WHOLE HALF OF THEIR BODY FOR A FEW MINUTES OR PERHAPS EVEN LONGER IN THE COURSE OF A THERAPEUTIC PROCEDURE, WHEN THEY’RE LYING DOWN, OR SOMETIMES PUT TO SLEEP USING GENERAL ANESTHESIA. DOES THAT ANSWER YOUR QUESTION?>>WHAT DO YOU SEE AS LOOKING IN A CRYSTAL BALL, WHAT DO YOU SEE AS THE CHALLENGE AND THE FUTURE OF NON-SURGICAL TREATMENT OF HEART DISEASE, BE IT PEDIATRIC OR ADULT, WHATEVER, WHERE IS — WHAT’S OVER THE HORIZON? DO YOU SEE?>>THE QUESTION IS WHAT ARE SOME FUTURE THERAPIES IN CATHETER TREATMENT? THERE ARE LOTS OF MORE SPECIFIC DISEASES THAT CAN BE TREATED BY MINIATURIZED OR TEMPORARILY MINIATURIZED DEVICES. VALVES CAN BE REPAIRED THAT HADN’T BEEN REPAIRED SO FAR. LEAKY MITRAL VALVES. VALVES COULD BE REPLACED IN STAGES USING MECHANICAL AND CATHETER TECHNIQUES. VARIOUS APPROACHES TO BIOLOGIC THERAPY USING MECHANICAL TECHNIQUES TO HELP REGENERATE DYSFUNCTIONAL MYOCARD YUM OR INFARCTED MYOCARDIMU OR PERHAPS TO FACILITATE REPLACEMENT OF ARTIFICIAL MEMBRANES OR CONDUIT WITH CELLS TO ACHIEVE ARTERIALIZATION. I PERSONALLY IN MY LAB HAD A GOING OUT OF BIOLOGICS SALE ABOUT 10 YEARS AGO BECAUSE I THOUGHT I AS A PHYSICIAN HAD VERY LITTLE TO ADD APART FROM ACTING AS A MAIL MAN TO DELIVER STUFF TO THE HEART, AND I THINK OUR LEVEL OF UNDERSTANDING HAS NOT REALLY ADVANCED TO THE STAGE OF PLAUSIBLE THERAPEUTICS IN MY HUMBLE OPINION, SO I DON’T REGRET THE DECISION I MADE 10 YEARS AGO. ONE OF THE CHALLENGES WE’RE GOING TO FACE, HOWEVER, IS FINANCIAL. YOU SEE THESE TEMPORARY DISPOSABLE DEVICES CAUSING TENS AND HUNDREDS OF THOUSANDS OF DOLLARS, CAN BE APPLIED LIKE WATER AND CAN BE IMMINENTLY LIFE SAVING. SO I SEE REAL CHALLENGES IN HOW WE’RE GOING TO BE ABLE TO OFFER CARE TO PATIENTS IN NEED UNLESS WE FIND WAYS TO MAKE THESE THINGS MORE AFFORDABLE, AND, IN FACT, MAYBE ADVANCED TECHNOLOGY OR BIOLOGICAL THERAPIES CAN HELP ACHIEVE SOME LIMIT — SOME REDUCTION IN THESE FANTASTIC COSTS THAT WE’RE ENDURING.>>WHAT DO YOU SEE IN TERMS OF FETAL SURGERY FOR CONGENITAL HEART DISEASE?>>YOU ASKED ME ABOUT THIS EARLIER, WHAT IS THE ROLE OF FETAL SURGERY IN CONGENITAL HEART DISEASE. THE MOST FAMOUS WORK OUT OF CHILDREN’S HOSPITAL BOSTON HAS ATTEMPTED TO ALTER THE HORRENDOUS NATURAL HISTORY OF CERTAIN CONGENITAL HEART DISEASES BY, FOR EXAMPLE, TREATING CELL STENOSIS IN UTERO, UNFORTUNATELY THE RESULTS ARE REALLY MUDDY. IT’S NOT CLEAR THEY’VE SUCCEEDED IN THEIR EARLY GOAL. THESE CHILDREN DON’T NECESSARILY HAVE AN EXCELLENT OUTCOME AND IT’S BEEN INTERESTING THAT THEY’VE BEEN ABLE TO ENHANCE THE AVAILABLE TOOLS, PERHAPS NOT NECESSARILY BENEFITING INDIVIDUAL CHILDREN. EVERYONE REMAINS VERY EXCITED ABOUT THESE THERAPEUTIC OPTIONS, PERHAPS AS WE HAVE BETTER IMAGING TOOLS, YOU MIGHT HAVE A MORE ENCOURAGING REPORT. DO YOU THINK, DR. PEARSON, WHAT I SAID IS FAIR? WOULD YOU LIKE TO EXPOUND ON THAT?>>I THINK YOU SHOULD.>>I DON’T KNOW IF I HAVE A LOT TO EXPAND, BUT AS I MENTIONED IN 1944, PEOPLE THOUGHT HEART SURGERY WAS COMPLETELY OFF LIMITS, SO NOW WE SORT OF THINK OF THE FETUS AS BEING OFF LIMITS IN A WAY, AND ALSO FETAL PRETOURS HAVE THE POTENTIAL FOR 200% MORTALITY IF SOMETHING GOES WRONG SO THAT’S SOMETHING YOU WANT TO UNDERTAKE — YOU DON’T WANT TO UNDERTAKE LIGHTLY, BUT I COULD ENVISION THE POTENTIAL FOR STEM CELLS IN THE FETUS MAYBE, FOR THINGS THAT COULD BE IMPLANTED THAT GROW. NOW AGAIN, THE HEART FORMS BY EIGHT WEEKS. UNLESS WE CAN SOMEHOW WORK ON MOLECULAR SWITCHES WHILE THE HEART IS DEVELOPING, THAT MIGHT BE WIT 50 YEARS DOWN THE PIKE,
WE’RE NOT GOING TO REALLY INFLUENCE THE HEART, BUT THERE ARE SOME THINGS THAT DO GET WORSE IN UTERO THAT MAYBE WE COULD HAVE SOME ROLE IN. AT THE MOMENT, THE MAIN THING WE CAN TREAT INROUTE YOUTH ROW IS FETAL ARRHYTHMIAS BY GIVING THE MOM SO MUCH MEDICINE IT MAKES THE ADULT CARDIOLOGISTS NERVOUS, ENOUGH SO THAT THE MEDICINE CROSSES TO THE FETUS. THIS IS OFTEN VERY EFFECTIVE, THESE ARE, OF COURSE, RARE CONDITIONS. I THINK THERE’S REASON TO BE CAUTIOUS BUT ALSO MAYBE REASON TO PRESS AHEAD BECAUSE WE DON’T REALLY KNOW WHERE THE NEXT FRONTIER IS.>>OTHER QUESTIONS? YES.>>I JUST WANT TO ASK MAYBE FOR REALLY ANY OF YOU BUT WHAT DO YOU SEE AS THE NEXT FRONTIER IN ADULT CONGENITAL HEART TREATMENT AND PERHAPS EITHER AT A SURGICAL OR IMMUNOLOGICAL TRANSPLANTATION, EVEN XENOGRAFT TALK NOW. WHAT DO YOU SEE AS THE NEXT BREAK THROUGH IN ADULT CONGENITAL THERAPIES?>>I’LL VENTURE IT AS ONE RESPONSE. THE FONTAN CIRCULATION THAT WAS INTRODUCED TO YOU WHERE PATIENTS ARE EB ABLE ENABLED TO SURVIVE
BEYOND CHILDHOOD BY REPLACING THE RIGHT VENTRICLE AS AN ACTIVE PUMP WITH JUST A PASSIVE CON TEUT, THE VENOUS CIRCULATION, THERE WAS A QUESTION HOW CAN THAT POSSIBLY WORK. EXACTLY, AND IT DOESN’T WORK SO WELL, I THINK THERE’S A HUGE UNMET NEED. NOW YOU’VE ASKED FOR A SOLUTION AND A FRONTIER. I HAVE REITERATED A PROBLEM. IT’S A FASCINATING PROBLEM, AND THERE ARE A LOT OF PHENOMENA THAT CAN BE EXPLOITED TO ENHANCE A FONTAN PUMP. PERHAPS IT WOULD BE THE RESPIRATORY MECHANICS SYSTEM, PERHAPS IT WOULD BE NEIGHBORING INTRINSIC PUMPS, MAYBE IT WOULD BE EXTRINSIC PUMPS.>>MAYBE IT WOULD BE PUMPS THAT YOU PLACE UNDER MRI GUIDANCE WITH A CATHETER.>>AND THEN TAKE LOTS OF PRETTY PICTURES OF. I THINK WHATEVER IT IS, I MEAN, NOT TO KEEP TOOTING THE IMAGING HORN, BUT THE INTERESTING — I THINK THE INTERESTING THING ABOUT ADULT CONGENITAL HEART DISEASE, PARTICULARLY WITH COMPLEX DEFECTS, YOU KNOW, PEOPLE BORN 20 OR 30 OR 40 YEARS AGO WITH THE SAME CONGENITAL HEART DEFECT COULD HAVE ANY ONE OF A NUMBER OF SURGERIES AND SO I DON’T KNOW THAT THERE’S ONE NECESSARILY SOLUTION ON THE HORIZON, SO I THINK IT DOES COME BACK TO INDIVIDUALIZED LIKE TAYLORS PLANS TO IMPROVE CIRCULATION BECAUSE REALLY IT’S THE OTHER END ORGANS THAT SUFFER THE MOST.>>I THINK THE WORK THAT LAURA AND ROBERT ARE DOING IS GOING TO CREATE A NEW GENERATION OF ADULTS WITH CONGENITAL HEART DISEASE WHO ARE IN MUCH BETTER SHAPE THAN THE CURRENT GENERATION. I THINK WE’VE MADE A MISTAKE AS CLINICIANS COLLECTIVELY TOO BY RESTRICTING PEOPLE WITH CONGENITAL HEART DISEASE FROM EXERCISING. SO IT’S PRETTY CLEAR THAT IF YOU CAN KEEP EXERCISING TO SOME EXTENT AND KEEP FIT, IT’S PROBABLY BETTER FOR YOU, AND IT’S CERTAINLY REASONABLY SAFE. SO ONE OF THE ISSUES THAT ADULTS HAVE IS THEY DECREASE EXERCISE TOLERANCE. I THINK WE ALSO NEED TO UNDERSTAND BETTER THE EFFECTS AS LAURA ALLUDED TO OF THE FONTAN CIRCULATION AND OTHER UNNATURAL CIRCULATION ON OTHER ORGANS LIKE THE LIVER. MOST ADULTS WITH THE FONTAN CIRCULATION HAVE LIVER DISEASE. AND WE DON’T REALLY KNOW WHY, WE CAN GUESS WHY BUT WE DON’T REALLY KNOW WHAT TO DO ABOUT IT.>> — THE HEART.>>WE THOUGHT OF THAT.>>LISTEN, THANK YOU VERY, VERY MUCH. THAT WAS VERY EXCITING. [APPLAUSE]

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