A Johns Hopkins study has raised doubts about a
long-accepted notion of what's going on in many cases of
heart failure, suggesting that nearly half of patients with
the disorder may be getting the wrong treatment for their
A team of Johns Hopkins scientists found that people
with so-called nonsystolic heart failure — marked by
relatively normal pumping action — do not have a
problem with refilling of the heart after the heart
contracts and squeezes blood out. During exercise, the
heartbeat does not increase as expected, which limits the
capability of these patients to pump blood to the body.
Their findings suggest that these patients might be
better off without beta blockers that slow down the heart
and worsen blood vessel function. Instead, they may benefit
from therapies such as pacemakers to speed up the heartbeat
or drugs that enhance blood vessel dilation.
The results may also help explain why some people with
heart failure and relatively normal pumping ability still
have severe fatigue performing the simplest of daily
Although preliminary, the findings "could dramatically
change the way we initially treat patients with this kind of
heart failure, because a cornerstone of current therapy is
the use of beta blockers that slow down the heartbeat and
decrease the strength of contraction," says lead study
investigator and cardiologist Barry Borlaug.
cardiology research fellow at the School of Medicine and
Heart Institute, presented the study results at the
American Heart Association's annual Scientific Sessions on
Nov. 15 in Dallas.
In the study, the Johns Hopkins team challenged the
commonly held belief that if heart-failure patients have a
normal ability to pump and squeeze blood to the rest of the
body (systolic function), then by "default" their hearts
have a damaged ability to relax and fill up with blood after
contraction (nonsystolic, or diastolic function). More than
5 million Americans are estimated to have some form of
congestive heart failure, marked by symptoms such as
shortness of breath and fatigue. An estimated 40 percent are
diagnosed with nonsystolic heart failure.
The Johns Hopkins team found that when all study
participants exercised at increasing levels, their hearts
filled with blood in a similar way. However, heart function
quickly failed to adjust to the increased activity in
patients with heart-failure symptoms. At peak exercise
levels, the ejection fraction, or squeezing function, was
also compromised in patients whose disease was traditionally
thought to be diastolic in nature. The study is believed to
be one of the first to examine patients with the nonsystolic
kind of heart failure by a head-to-head comparison with
patients having similar features, such as high blood
pressure and hypertrophied, or overgrown, hearts, but no
symptoms of heart failure.
"Our results challenge conventional wisdom, showing
that congestive heart-failure patients who early in their
disease have a normal ejection fraction may refill properly
but also have markedly impaired capacity to carry blood
around with enough force to perform the most basic of daily
activities, such as getting dressed in the morning," said
senior study investigator David Kass, the Abraham and
Virginia Weiss Professor of Cardiology. "There is a quite
different biological mechanism at work than what was thought
to be the case."
In the study, 19 elderly women and men, mostly
African-Americans from the Baltimore area, were matched to
17 adults similar in age and risk factors for heart failure:
obesity, high blood pressure and enlarged hearts
(hypertrophy). All 36 had a slightly elevated ejection
fraction of approximately 70 percent. Most had diabetes, and
many were already taking medications for their conditions,
which were temporarily withheld until the study was
finished. The nonsystolic kind of heart failure is known to
disproportionately affect the elderly, women and blacks. A
key feature of the study was that the 17 comparison patients
also had chronic health problems, such as high blood
pressure, diabetes and hypertrophied hearts — factors
that can also impair heart function.
Using a standard exercise stress test, both groups
exercised on stationary bicycles to the point of exhaustion,
starting slowly and increasing speed every three minutes.
Heart function was monitored by radiology imaging, along
with blood pressure, respiratory gases and fluid samples
taken before and after testing.
Differences between the heart failure group and the
control group were observed early on in the study and at
relatively low levels of exercise, 25 watts, roughly the
equivalent amount of energy required to get dressed. In the
control group, heart rate jumped by 40 percent but rose only
by 20 percent in the heart-failure group. Corresponding
drops in vascular resistance, the force inside the blood
vessels that resists blood flow, were 28 percent in controls
but only 19 percent in the heart-failure group. Increases in
cardiac output, the amount of blood circulating in the body
at any one time, were also greater in the control group, at
62 percent, than in the heart-failure group, at 39
Meanwhile, increases in blood volume to the heart, when
filling, remained the same between the two groups.
And, while squeezing function increased similarly in
both groups at very low levels of exercise, differences
emerged at peak activity. All measures of heart function
during contraction worsened to a greater extent in the
heart-failure group at peak exercise, except those related
to diastolic function.
Heart rates in the control group rose threefold more
than in the heart-failure group. Ejection fraction, an
indicator of contractility or muscle strength, rose by 9
percent in controls and 4 percent in the heart-failure
group, despite being similar at the start of the test.
Overall, the control group had an exercise capacity of
72 percent of what was expected for their age, while the
heart-failure group had only 50 percent. Measures of hormone
levels and volume of blood in the lungs, a factor in making
people of short of breath as a symptom of the disease,
increased to similar levels in both groups: 50 percent and
10 percent, respectively.
While the exact cause of these differences in heart
failure remains unknown, the scientists hope that dispelling
popular misconceptions is the first step in their research.
Kass said, "It is essential that we get to the root cause of
this problem because at some point, more than half of all
patients with either kind of heart failure will be
readmitted to the hospital."
Funding for this study was provided by the National
Institutes of Health and the Peter Belfer Laboratory
Other researchers involved in this study, conducted
solely at Hopkins, were Vojtech Melenovsky, Laura Shively,
Kristy Swigert and Lewis Becker.