>> CONGENITAL HEART DISEASE, BY DEFINITION,
IS RELATED TO GENETICS IN SOME WAY.
>> IT'S REALLY ON THE CUTTING-EDGE OF RESEARCH
RIGHT NOW TO TRY TO UNDERSTAND THIS DISORDER.
>> THESE ARE COMPLEX LESIONS WHICH ARE PROBABLY NOT
CAUSED BY ANY SINGLE GENE OR ANY SINGLE THING.
>> EVEN THOUGH MOTHERS KNOW THE FACTS,
THERE'S ALWAYS THIS SORT OF FEELING OF GUILT,
LIKE DID THEY DO SOMETHING WRONG DURING PREGNANCY,
WHICH ISN'T TRUE.
AND THE MORE WE CAN PULL ALONG THE GENETIC COMPONENT
TO THIS, I THINK THAT WILL ALSO HELP IN THE
UNDERSTANDING OF HOW CONGENITAL HEART DISEASE
DEVELOPS.
>> ONCE WE FIGURE OUT THE PRECISE MECHANISM,
THAT IS, THE PRECISE MOLECULAR MECHANISM BY WHICH
THESE OCCUR, WE CAN BOTH PREDICT HOW PEOPLE WILL DO
AS WELL AS DESIGN THERAPIES IN ORDER TO TRY TO CURE
THESE DISEASES BEFORE THEY OCCUR.
>> THE HEART IS ESSENTIALLY FULLY FORMED BY 6 TO 8
WEEKS' GESTATION.
THE SIGNALS THAT DETERMINE THE NORMAL DEVELOPMENT,
COMPLETION OF DEVELOPMENT OF THE HEART,
ARE THE GENES.
>> OUR GENES ARE WHAT THEY CALL THE BLUEPRINT FOR WHAT
WE'RE GOING TO LOOK LIKE.
SO THE PROGRAM FOR CARDIOVASCULAR DEVELOPMENT
IS SET ONCE THE GENES ARE THERE TO MAKE THE EMBRYO,
IF YOU WILL.
THEY DIRECT HOW THE EMBRYO IS GOING TO DEVELOP.
THEY DIRECT HOW THE FETUS IS THEN GOING TO CONTINUE
TO DEVELOP.
>> IF YOU THINK OF ALL THE BILLIONS OF THINGS THAT HAVE
TO HAPPEN, ONE RIGHT AFTER ANOTHER,
TO HAVE A BABY DEVELOP TO WHAT WE CONSIDER TO BE
NORMAL, IT'S JUST AMAZING TO ME THAT MORE THINGS
DON'T GO WRONG.
AND MOST CONGENITAL HEART DEFECTS ARE BECAUSE,
AS THE HEART IS FORMING IN THE FIRST MONTH OR SO OF
PREGNANCY, CERTAIN PARTS THAT COME TOGETHER COME
TOGETHER IN A SLIGHTLY OFF-KILTER WAY.
>> EARLY, EARLY ON, WHEN THE EMBRYO IS FIRST A CELL
AND THEN DIVIDES AND THEN DIVIDES SOME MORE,
YOU GET TO A STAGE WHERE THERE ARE ACTUALLY CELLS
THAT DON'T LOOK ANYTHING LIKE A HEART YET BUT THAT
HAVE COMMITTED THEMSELVES TO BECOMING A HEART.
>> IT BEGINS AS A SINGLE TUBE WHICH ROTATES AND FOLDS
TO FORM THE FOUR CHAMBERS THAT WE SEE AND THEN
THE BLOOD VESSELS THAT COME OFF, GOING TO THE BODY
AND TO THE LUNG.
>> SO YOU CAN HAVE A HEART DEFECT DEVELOP BECAUSE
THE PARTITION BETWEEN THE TWO SIDES OF THE HEART,
INSTEAD OF FORMING AT A CERTAIN ANGLE,
FORMS AT A SLIGHTLY DIFFERENT ANGLE.
AND THAT'S ALL IT TAKES TO CREATE ONE OF THE MORE
COMMON TYPES OF CONGENITAL HEART DISEASE CALLED
TETRALOGY OF FALLOT.
WHEN THE ARTERY OF THE BODY AND THE LUNGS FORM,
THEY FORM AND SEPARATE AND THEY TWIST AGAINST
EACH OTHER.
AND IF THEY DON'T TWIST JUST RIGHT,
YOU CAN HAVE SEVERAL OTHER TYPES OF CONGENITAL HEART
DEFECTS FORM.
SO SINCE ALL OF THESE THINGS ARE INTERRELATED,
IT'S NOT CLEAR THAT THERE'S A SPECIFIC GENE DEFECT
THAT CAUSES EACH ONE OF THESE CONGENITAL HEART
ABNORMALITIES.
>> INSTEAD, THERE ARE GOING TO BE A LOT OF DIFFERENT
GENES AND A LOT OF DIFFERENT CHANGES IN THOSE GENES
THAT CONTRIBUTE TO THE RISK OF HAVING A CHILD
WITH A HEART DEFECT.
>> TAKING CARE OF THESE CHILDREN IS A UNIQUE
OPPORTUNITY TO LEARN WHY THEY HAVE THE CONGENITAL
HEART DEFECT.
WHAT CAN WE DO TO MAKE THEM BETTER,
NOT JUST IN THE SHORT-TERM BUT IN THE LONG-TERM.
>> ONE OF THE OBLIGATIONS AS WELL AS THE PRIVILEGES
OF HAVING A CENTER LIKE THIS IS TO IDENTIFY THE UNANSWERED
QUESTIONS IN ALL OUR SPECIALTIES AND TO WORK
COLLECTIVELY WITH THE FAMILIES AND WITH OUR
COLLEAGUES TO GET THESE QUESTIONS ANSWERED.
>> THE RESEARCH EFFORT, JUST LIKE EVERYTHING ELSE,
IS A TEAM EFFORT.
>> EVERYBODY FROM CLINICAL RESEARCHERS WHO COLLECT
DETAILED DATA IN THE INTENSIVE CARE UNIT AS WELL
AS OUTPATIENT CLINICS, TO RESEARCH NURSES WHO LOOK AT
ALL THE INTERMEDIATE TYPE OF INFORMATION YOU CAN GATHER
FROM AN OPERATING ROOM, TO PEOPLE LIKE MYSELF WHO STUDY
THESE TYPE OF DISEASES IN THE LABORATORY,
AS WELL--
>> AND IT'S NOT JUST THE NURSES,
THE PHYSICIANS, THE INVESTIGATORS.
IT'S THE FAMILIES AND THE CHILDREN ARE AN INTEGRAL
PART OF THAT TEAM.
>> I'M AMAZED ON A DAILY BASIS OF THE STRENGTH AND
COMMITMENT OF FAMILIES, NOT ONLY TO THEIR CHILDREN
BUT TO THE RESEARCH AT CHOP.
>> YOU TALK TO THE FAMILIES.
IT'S JUST REALLY AMAZING HOW THEY'RE REALLY ENGAGED IN
THE HEART DISEASE AND MOVING THE FIELD FORWARD.
>> SHE'S AS HEALTHY AS SHE IS TODAY BECAUSE THERE HAVE
BEEN OTHER KIDS THAT HAVE AGREED TO BE IN STUDIES.
>> AND SO THERE ARE A LOT OF RESEARCH PROJECTS.
SOME OF THEM ARE VERY MINOR, JUST A SMALL DROP OF BLOOD
SO WE CAN TRY AND FIGURE OUT WHY THE CHILDREN
HAVE HEART DISEASE.
SOME OF THEM ARE MORE ELABORATE--
>> SO THAT THE CHILD CAN BE FOLLOWED DURING THEIR
DEVELOPMENT.
THAT'S TAKES A LOT OF COMMITMENT ON THE PART
OF FAMILIES.
>> WHAT WE'RE DOING NOW IS A RESULT OF ONGOING
INVESTIGATION, ONGOING ABILITY TO TRY NEW THINGS
AND LOOKING AT DIFFERENT WAYS TO TREAT CHILDREN
WITH HEART DISEASE.
>> THE CENTER FOR APPLIED GENOMICS WAS SET UP AT CHOP
AND IS A VERY HIGH THROUGHPUT GENOTYPING
FACILITY THAT GIVES US THE OPPORTUNITY TO HAVE INSIGHT
INTO THESE DISEASES THAT VERY FEW PLACES IN THE WORLD
WILL REALLY BE ABLE TO DO.
>> TO IDENTIFY SPECIFIC GENES AND SAY GENE X
OR GENE Y IS GOING TO RESULT POTENTIALLY IN A DIFFERENCE,
AND THEN OBSERVE THAT DIFFERENCE.
>> IF WE CAN IDENTIFY A SPECIFIC PROBLEM,
THEN MAYBE WE CAN TREAT YOU DIFFERENTLY.
>> SO THAT THE WORST CASE SCENARIO DOESN'T OCCUR,
BUT MAYBE SOMETHING THAT'S A LITTLE BIT MORE AMENABLE
TO THERAPY AND TO A GOOD OUTCOME COULD OCCUR.
>> I THINK WE'LL GET TO A POINT WHERE WE CAN IDENTIFY
CERTAIN GENETIC FEATURES OF EACH INDIVIDUAL CHILD THAT
WILL ENABLE US TO MODIFY HOW WE DO AN OPERATION.
>> TO REALLY FOCUS ON PROTECTING THE BRAIN THROUGH
THIS VULNERABLE PERIOD.
>> TO LOOK AT EACH ANESTHETIC AS
CUSTOM-TAILORED.
>> TO TRY TO TAKE THE MOST NOVEL,
FAR REACHING, CUTTING-EDGE APPROACHES TO PROVIDE
A WONDERFUL OUTCOME AND FUTURE FOR THE CHILDREN
AND FAMILIES.