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The newspaper of The Johns Hopkins University November 28, 2005 | Vol. 35 No. 12
Johns Hopkins Study May Change Rules for Treating Heart Failure

Discovery suggests that some patients on beta blockers should not be

By David March
Johns Hopkins Medicine

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 disease.

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 tasks.

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.

Borlaug, a cardiology research fellow at the School of Medicine and its 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 percent.

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 Foundation.

Other researchers involved in this study, conducted solely at Hopkins, were Vojtech Melenovsky, Laura Shively, Kristy Swigert and Lewis Becker.


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