My Adventures with Heart Failure

A couple of recent articles about heart failure from Business Week. Business Week???? Not where I would have expected them, but hey, let's be glad people are finally noticing we're out there.

Spotting Heart Disease Early
MARCH 6, 2006
Heart Health
By Kerry Capell

Spotting Heart Disease Early
Roche and other companies are devising diagnostic tests that help more
patients prevent heart attacks. The next frontier: genetics-based screens

Diagnosing heart failure is time-consuming, expensive, and often inaccurate.
The condition, which occurs when the heart is unable to pump enough blood
throughout the body, afflicts 5 million Americans, with 550,000 new cases
reported each year. But its symptoms -- shortness of breath, swollen ankles,
and fatigue -- are vague and easily confused with other conditions such as
lung or kidney problems. This complicates and delays diagnosis while
increasing the chances of error. Missing a heart failure diagnosis puts
patients at high risk of serious problems -- or death -- while overdiagnosis
may lead patients to receive unnecessary and costly treatment.

BIG BREAKTHROUGH. Now, with a simple blood test, doctors can accurately
diagnose or rule out heart failure in minutes. Launched two years ago by
Swiss drug and diagnostics giant Roche Holding (RHHVF), the test measures
the levels of two proteins, NT and BNP, which are elevated when the heart
muscle is under stress. Levels of these proteins can be raised in cases of
heart failure, heart attack, unstable angina, pulmonary embolism, and acute
high blood pressure.

Initially, the test was used to diagnose heart failure and monitor its
treatment. But last month researchers at Massachusetts General Hospital made
a major breakthrough.

In clinical trials, the test proved able to predict long-term risk of death
in patients with shortness of breath. The researchers found that patients
with elevated levels of the proteins, regardless of the cause, had a higher
risk of dying within one year.

"CONSIDERABLE RISK." As a result, they believe the test can be used not
only to determine diagnosis but also to gauge long-term prognosis, allowing
doctors to quickly identify patients needing more aggressive treatment and
follow-up.

"The next logical step is to evaluate treatment interventions for those with
higher NT-proBNP levels to see if we can reduce their considerable risk for
death," says Dr. James Januzzi Jr., assistant professor of medicine at
Harvard Medical School and a staff cardiologist at Massachusetts General
Hospital, who led the research.

Such tests represent a major advance in the diagnosis of cardiovascular
disease. Led by Roche, the world leader in cardiovascular testing, many
companies now have diagnostic tools on the market to both measure a
patient's risk of heart disease and detect existing heart disease. More
tests can then distinguish the exact type of disease.

WORST OF THE WORST. For instance, Roche was the first company to introduce
a blood test for troponin, a protein released from dead or injured cells in
the heart muscle. This test can determine not only whether a patient has had
a heart attack but the exact extent of damage to the heart muscles.

Roche is now taking a much closer look at traditional risk factors for
cardiovascular disease such as cholesterol, in the hopes of developing
diagnostics that can pick up heart disease much earlier. So instead of just
looking at LDL, the so-called bad cholesterol, the company is looking at the
worst of the worst subsets of LDL to find very early indications of clogged
arteries, says Dr. Hendrik Hüdig, head of Roche Centralized Diagnostics'
marker program.

But pharmaceutical and diagnostic companies are moving beyond such
traditional markers and exploring a range of proteins and genetic mutations
to develop more sophisticated tools to enable earlier and more accurate
diagnosis.

PRECISE TARGETING. "What we're researching is how to assess which patients
are at risk, when will they develop heart disease, how their disease is
progressing, and whether treatment can be monitored," says Dr. Joachim
Eberle, head of research and development at Roche Centralized Diagnostics.

Diagnostics is the first frontier in the ongoing quest for personalized
medicine. But as scientists discover more about the exact proteins and genes
involved in specific forms of heart disease, they will in turn discover
potential targets for better and more effective medicines.

In the meantime, diagnostics companies are in a race to develop
sophisticated tests to target with greater precision those most at risk for
heart disease. It has proved a hard slog, since heart disease is not one
disease but many, which are caused by a complex combination of genetics and
environment.

GENETIC RISK SCORE. But Celera, an Alameda (Calif.) biotech co-founded by
genomics pioneer J. Craig Venter, is on the verge of introducing a new blood
test to help predict whether a patient has a high or low risk of developing
heart disease, independent of traditional risk factors such as high
cholesterol or diabetes.

In conjunction with researchers at Harvard, the Cleveland Clinic, the
University of California at San Francisco, and the University of Texas,
Celera has examined the genetic profiles of more than 30,000 patients. By
comparing genetic samples of patients who have had heart attacks with those
who haven't, they have found a number of novel genetic variations that
contribute to the development of coronary heart disease.

These variations form the basis of Celera's genetic risk score, which the
company says will be available in "a matter of months, not years." "People
will be able to determine definitively whether they carry incremental risk
for heart attack," says Celera President Kathy P. Ordonez.

NO SYMPTOMS. Such knowledge could even lead to preventative treatment. For
instance, patients who have no symptoms of heart disease but have a high
genetic risk score might be given cholesterol-lowering statins.

Currently, most doctors prescribe statins to patients exhibiting more than
two of the standard risk factors such as high blood pressure, high
cholesterol, or obesity. But as Ordonez points out, are more than 17 million
Americans fall into the category of moderate risk and therefore wouldn¹t be
treated. If these patients were armed with their genetic risk score, doctors
could intervene earlier and stop heart disease in its tracks.

Capell is a senior writer in BusinessWeek's London bureau

The only problem I see with the above is that the tests for NT and BNP wouldn't necessarily catch everyone, no matter what the article says. My BNP levels are completely normal. If that were a required criterion for diagnosis, I would still not be properly diagnosed.

Heart, Heal Thyself?
MARCH 3, 2006
Heart Health
By Catherine Arnst

Heart, Heal Thyself?
So far, stem cells have not delivered the results scientists hoped for. But
excitement is still rising

The dream of medical science is to train the body to repair itself in the
face of disease or trauma, and the main focus of this dream is the heart.
For five years, teams of doctors around the world have been trying to coax
adult stem cells, the body's innate repair kit, to regenerate damaged heart
tissue after a heart attack or other coronary disease.

These efforts have generated excitement among heart specialists, despite the
fact that clinical trial results have been uneven and no one is quite sure
how, why, or even if, stem cell therapy works. The excitement continues to
mount, despite a study released on Mar. 1 stating that one of the most
widely examined methods for delivering stem cells to the heart had failed.

BONE MARROW. A team of German doctors from Technische Universitat in Munich
reported on a rigorously conducted trial in the Journal of American Medical
Association (JAMA). Scientists injected G-CSF, a human growth factor known
to stimulate adult stem cells, within 12 hours after a heart attack.

There were 114 patients in the study, more participants than the three
earlier G-CSF trials combined. Half received the treatment, and the other
half were given a placebo. After six months of follow-up, the researchers
discovered that G-CSF did prod a significant number of stem cells to move
from the bone marrow, where they are produced, to the heart, with no serious
side effects.

Nonetheless, there was no improvement in heart function, throwing doubt on
the whole stem cell approach. "The answer is fairly unequivocal," says Dr.
Kenneth Chien, director of the cardiovascular research center at
Massachusetts General Hospital in Boston. "The stem cells did not improve
function."

DIRECT DELIVERY. Unequivocal or not, the failure of the German trial has
not dampened enthusiasm for heart regeneration. Several reports on stem cell
research will be highlighted at the American College of Cardiology meeting
in Atlanta on Mar. 11-14, and teams of doctors and biotech companies around
the world are continuing their research in this area.

Most are quick to point out that their methods are fundamentally different
from the German approach. If anything, the failure of G-CSF turned more
attention on the many efforts to deliver stem cells directly to the heart,
rather than indirectly trying to stimulate them with a growth factor.

There have been no human studies of the direct approach on the scale of the
German trial, and the many smaller studies have often been contradictory.
But even Chien, who considers himself a conservative when it comes to stem
cell therapy, says it is one of the more exciting areas of heart research.
"I don't think it should be considered a slam dunk, but I do think it is
promising long-term."

SHAPE SHIFTERS. Stem cell researchers, many of whom also treat patients,
are driven by a huge unmet need. Some 1.1 million Americans are struck by
heart attacks each year, and 4.8 million suffer from congestive heart
failure, in which the heart stops pumping effectively, with 400,000 new
cases diagnosed each year.

Both these conditions are caused by the destruction of heart muscle cells,
and there are few effective therapies that can counteract that damage.
Unlike most other tissues in the body, the heart does not regenerate itself.
When damage occurs, it merely grows scar tissue, which restricts pumping
even further.

Stem cells seem like an obvious solution. In an embryo, stem cells, which
are undefined, can turn into any tissue in the body.

Because of restrictions and ethical concerns about the use of embryonic stem
cells, however, most heart experiments involve adult stem cells extracted
from the bone marrow. The pioneers in this area are Drs. James T. Willerson
and Emerson C. Perin of the Texas Heart Institute at St. Luke's Hospital in
Houston.

ALMOST DOUBLE. In 2000, Willerson and Perin treated 14 Brazilian patients
with stem cells removed from their hip bones and directly injected with a
catheter to their damaged hearts. Within two months, the patients
demonstrated improved heart function, with almost double the pumping motion
in those parts where the cells were injected.

When one of those patients died 11 months after treatment, of unrelated
causes, the doctors discovered during an autopsy that there was clear
evidence of new blood vessel formation to the heart.

The team is now conducting a U.S. trial with 25 patients, and recently won
approval for another trial. "We realize that we've not identified the best
stem cells, or the best method of administration," says Willerson. "We don't
want to be part of the hype, but this is an exciting time."

SMALL SAMPLE. Willerson and Perin are using the patient's own adult stem
cells to avoid rejection by the body's immune system. But a small biotech in
Baltimore, Osiris Therapeutics, is aiming to come up with a more universal
approach by using donated mesenchymal stem cells (MSC).

These are universal to everyone, so they do not set off an immune reaction.
Animal studies indicate that the MSCs are prompted by inflammatory signals
to head to the site of an injury, and Osiris recently started a Food & Drug
Administration-sanctioned clinical trial to test the therapy in heart attack
patients.

Then there are stem cells that actually originate in the heart, discovered
only two years ago. These cardiac stem cells exist in very small numbers,
but doctors at Johns Hopkins School of Medicine have figured out how to
harvest them by taking a small tissue sample from the heart and then growing
them in culture.

FIRST PAGE. The cells have not yet been tested in humans, but when injected
into animals they appear to go straight to the heart and regenerate tissue,
says Dr. Eduardo Marban, chief of cardiology at Johns Hopkins. "The mystery
is: If these cells do work to heal the heart, how do they work?" questions
Marban. "We're reading the first page of a very long book here."

Long it may be, but Marban speculates that there could be evidence of
whether or not adult stem cells work in humans in a year or two. It will
certainly take longer to figure out why. There are many scientists in the
field who believe the stem cells may be merely "good neighbors" that are
prompting the heart's own healing process to kick into high gear.

That wouldn't be such a bad discovery, says Dr. David T. Scadden,
co-director of Harvard University's Stem Cell Institute. "In the short term
the stem cells may be providing something that reverses damage, but that
could lead to a whole new generation of studies into an off-the-shelf drug
that would perform the same function." In that dreamscape, heart attack
victims could just visit the pharmacy instead of the hospital.

Arnst is a senior writer for BusinessWeek in New York