of the Failing Heart
has been a principal investigator on more than 70 clinical
research studies in heart failure and other cardiovascular
Klapholz, MD, director of cardiology, UMDNJ-University Hospital,
and associate professor of medicine, UMDNJ-New Jersey Medical
Other people's hearts keep Marc Klapholz ticking
'round-the-clock. In fact, they're both his passion and his
lifeblood. He works to fix hearts whose rhythms are no longer
strong and steady, that falter and plummet and skip out of
control, damaged hearts too weak to pump enough blood for
the body's workings.
Klapholz calls curing heart failure one of
"the holy grails of medicine." This mission has enormous repercussions.
Five million people in the U.S. have failing hearts - unarguably
an epidemic. And the numbers are rising. There are more than
half a million new cases diagnosed annually. It's estimated
that advanced heart failure kills 20 percent within a year
of diagnosis, and 50 percent within five years. The growing
number of aging Americans - particularly those who survive
recurrent heart attacks, but with grave damage to their organs
- is the largest contributor to the escalating numbers. Uncontrolled,
or undiagnosed, high blood pressure is also a major player.
Sometimes there is no identifiable cause.
Heart failure does not mean the heart has
stopped or threatens an imminent shutdown, but that it has
been damaged. And since the pump cannot yet be fixed, Klapholz
says "the resistance against which the heart has to work needs
to be decreased and metabolic derangements that occur because
the pump is impaired need to be corrected." The symptoms -
chief among them difficulty breathing, extreme fatigue when
exercising and sometimes even at rest, and swelling of legs
and feet - often stop people in their tracks, setting off
alarms of dire illness that bring them panicked into the emergency
"To slow it down, prevent it, perhaps to reverse
it - what a tremendous challenge," says Klapholz. "Of course,
our ultimate goal is to stop this major killer."
As heart failure progresses, the question
of when to transplant is a valid one. Each year, 4,000 Americans
are sick enough to be placed on an urgent heart transplant
waiting list, but unfortunately, the organs are hard to come
by, and only 2,000 heart transplants are performed in this
country annually. In most cases, heart failure must be managed
by medications. As a cardiologist who specializes in the medical
management of this disease, Klapholz's aim is to find the
best drugs to do the job in each individual case. This is
a tough assignment.
While many do well on conventional therapies,
Klapholz says the "art is in combining drugs and knowing how
to work with dosages, and being able to tell when a person's
condition is worsening even slightly," which warrants immediate
attention. But some patients are not responsive to the traditional
drugs or lose responsiveness over time, as the condition worsens.
It is these patients whom cardiologists refer to heart failure
specialists like Klapholz - who has been a principal investigator
on more than 70 clinical research studies in heart failure
and other cardiovascular diseases - for therapies not yet
Just recently, he participated in a major
clinical trial to determine the value of a drug specifically
aimed to treat heart failure in black patients. Called BiDil,
the drug was determined to be so effective that it was considered
unethical to continue giving some patients a placebo. The
clinical trial was halted early and all 1,050 participants
will be offered the medication. The drug will be going forward
for FDA approval, which may be granted as early as the beginning
There are an estimated 750,000 blacks with
heart failure and many are not being helped by the standard
medications. Blacks are more likely than whites to die of
the disease. BiDil works by enhancing the level of nitric
oxide, a gas that is released from the lining of arteries
and which may be more commonly deficient in black patients
with heart failure. "However," Klapholz cautions, "the differences
in terms of treating heart failure have to do with genetics,
not skin color."
Among his other recent efforts to diminish
the impact of heart failure was participation - as a principal
investigator - in a clinical trial of the novel compound tolvaptan,
a "selective vasopressin receptor antagonist." According to
Klapholz, it is a "fascinating drug that addresses fluid overload
that is part and parcel of heart failure."
There are roughly one million hospitalizations
yearly for chronic heart failure, most related to worsening
congestion, or fluid build-up, particularly in the lungs.
"Diuretics are used ubiquitously for this congestion but unfortunately
they are drugs with very bad side effects," he says. Diuretic
use is linked to electrolyte imbalances and worsening kidney
The congestive symptoms experienced by heart
failure patients may be due, in part, to elevated vasopressin
levels. By blocking the action of vasopressin, the experimental
drug was successful in lessening congestion in these patients
without having deleterious effects on blood pressure, heart
rate, potassium levels, or kidney function. Results of this
study were published this year in the Journal of the American
Medical Association. Klapholz was one of the authors. Further
studies are underway to ascertain if the drug actually extends
survival in heart failure patients.
Developing and heading up sites for national
and international research trials of new heart failure medicines
is only one facet of this cardiologist's work. He is also
board certified in echocardiography and interventional cardiology.
"I am trying to develop as much expertise as possible in many
areas," he says.
Klapholz, recently appointed director of cardiology
at UMDNJ's University Hospital and New Jersey Medical School,
plans to "grow a premier cardiology program here." He also
aims to develop new programs in pulmonary hypertension, percutaneous
cardiovascular defect repair (placing plugs to close up holes
in the heart), percutaneous left ventricular assist devices
(miniaturized pumps to support failing hearts) and peripheral
vascular disease management, including repair of blockages
in carotid arteries with the use of stents.
In addition, he believes a great opportunity
exists to partner with basic scientists at the Cardiovascular
Research Institute at UMDNJ-New Jersey Medical School to work
on cardiovascular repair. "We have the underpinnings of turning
around heart failure," he says. His goal is to establish UMDNJ
as a leading center in the country for the treatment of cardiovascular
He also looks forward to "developing a strong
relationship with the pharmaceutical industry, which is so
prominent in New Jersey, in the quest to develop new medications
for cardiovascular disease," he says. "I feel the sky's the
While Klapholz keeps his own heart exercised
by bicycling in Central Park, what really keeps him going
is the "drive to be very good at something in a context of
doing something of real value," he comments. Finding better
drugs to regenerate millions of failing hearts, while successfully
applying the standard therapies, is certainly a mission of
real value. "And working well with the people around me and
enjoying those interactions every day are also very important
to me," he says.
It is this total dedication to keeping the
hearts around him beating healthfully - and happily - that
makes him one of America's "top docs."