Advances in the treatment of heart failure

New treatments have turned heart failure into a condition that people can live with for many years.

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By  Harvard Medical School Published  November 8, 2005

|~||~||~|Heart failure sounds immediate and total — like power failure. But heart failure — often called congestive heart failure — doesn’t mean the heart suddenly stops. The term for that is cardiac arrest. Rather, it means that the heart can’t pump enough blood to meet the body’s needs because one or both ventricles (the heart’s main pumping chambers) are not functioning properly.

In many cases, they can’t pump with enough force (systolic heart failure). In others, the problem is an inability to draw enough blood in (diastolic heart failure). Often the weakened heart is also contending with constricted arteries and veins so it must work that much harder to push blood through the circulatory system.

The hallmark symptoms are shortness of breath (dyspnea), fatigue, swelling in the extremities (peripheral edema), and collection of fluid around the lungs (pleural effusion). Heart failure often occurs in the aftermath of other heart and vascular problems, so there are both cause and consequence to deal with. The conditions that can lead to heart failure include coronary artery disease (blockage of arteries supplying blood to heart muscle), high blood pressure, and heart valve defects.

Because of improved treatment, prognosis has improved and people are living noticeably longer with the condition. More often than not, these hearts are beating in older chests. So as the population in the Middle East and elsewhere ages, the number of patients may increase. Heart failure, like creaky joints and memory lapses, may be one of the prices we pay for longer life spans.

On the other hand, Mayo Clinic researchers and others have found that the number of newly diagnosed cases (incidence) of heart failure seems to be stable — and, according to a Framingham Heart Study analysis, may even be going down among women. Why? Possibly because some causes of heart failure, such as high blood pressure, are better treated than they used to be.

Medications
Just 25 years ago, there were only two main classes of medications for the treatment of heart failure: diuretics (water pills) and digitalis (digoxin). Diuretics rid the body of excess fluid by increasing urine flow. Digitalis, originally derived from the purple foxglove plant (Digitalis purpurea), has been used for treating heart disease since the 18th century. It widens blood vessels and increases the force of the heartbeat. Although both drugs relieve symptoms, they don’t have much impact on the death rate from heart failure.

Now myriad drugs are used for heart failure. Of all the ones that have come into use over the past couple of decades, the angiotensin-converting–enzyme (ACE) inhibitors are the most important. They’re the single biggest reason why heart failure has become a treatable condition rather than a death sentence. ACE inhibitors work by blocking the synthesis of angiotensin, a substance that constricts blood vessels, raises blood pressure, and puts strain on the heart. As a result, they slow the deterioration of the straining heart muscle.

Angiotensin-receptor blockers (ARBs) are an alternative for patients who can’t tolerate the side effects of ACE inhibitors. Like ACE inhibitors, they interfere with angiotensin, but in a different way. It’s not clear that they are as effective as ACE inhibitors, but they are much less likely to cause the dry cough that some people get from an ACE inhibitor.

Aldosterone, a hormone produced by the adrenal glands, increases blood volume and raises blood pressure. High levels of the hormone can damage heart muscle, causing it to become enlarged and develop stiff, fibrous tissue (cardiac fibrosis). Aldosterone antagonists, or blockers, counteract this effect, and also prod the kidneys to eliminate unneeded water and salt. Side effects can be a problem with spironolactone (Aldactone), the most widely used aldosterone antagonist. Eplerenone (Inspra), first approved by the FDA in 2002 for high blood pressure, is an alternative that seems to cause fewer side effects.

Causes of heart failure
Beta blockers interfere with the action of adrenaline and related compounds. They reduce high blood pressure, help correct irregular heartbeats, and reduce the heart’s workload. At first, doctors thought beta blockers might actually worsen heart failure and avoided prescribing them. Why slow down a weakened heart? But during the past 10 years, researchers discovered that if heart failure patients took ACE inhibitors and beta blockers together they lived longer.

As its pumping action becomes floppy and inefficient, a diseased ventricle leaves more blood behind, where it can pool in the heart chambers and form a clot, which could travel to the brain and cause a stroke. Anticoagulants, such as warfarin (Coumadin), are prescribed to prevent that.

Nesiritide (Natrecor) is a powerful intravenous drug that relaxes blood vessels and helps make the heart beat stronger. It was originally intended only for heart failure patients who were very ill (decompensated), but doctors started to prescribe serial infusions for patients after they left the hospital. After two studies raised questions about its safety, a panel of cardiologists chaired by Harvard Medical School’s Dr. Eugene Braunwald said it shouldn’t be used that way and recommended strictly limiting the drug to seriously ill patients arriving at the hospital. At the same time, the panel said a clinical trial in outpatients should continue.

Especially in the beginning, heart failure can often be well controlled with an ACE inhibitor and a beta blocker in combination with exercise, diet, and other lifestyle changes. Often, though, in more advanced cases the drug regimen gets complicated. It’s not uncommon for a patient with heart failure to be taking an ACE inhibitor, a so-called loop diuretic (Bumex, Lasix), digoxin (Lanoxin), an aldosterone antagonist (spironolactone or eplerenone), and a beta blocker.

These combinations do wonders, both relieving the symptoms of patients and helping them live longer. But as the mix becomes more complex, so does the tinkering and adjustment needed to get the desired effect. Interactions among drugs can be a problem. Doctors really need to know what they are doing — and know their patients. Needless to say, more drugs means more expense, both because newer medicines usually cost more, and because complicated drug schedules require more doctors’ appointments and lab tests.

Surgical procedures
When the valves that separate the chambers of the heart are defective, the heart can’t pump efficiently. Surgery to repair or replace valves is now fairly common. Coronary bypass surgery is normally used to treat a heart attack or angina patient who has narrowed or clogged coronary arteries. But it can also be used to treat heart failure patients.

The notion is that heart failure is sometimes caused by areas of the heart that don’t get enough blood to pump forcefully. By improving blood flow, bypass surgery will revive this “hibernating” tissue so it pumps more effectively. But doctors will try medications before even considering bypass. Moreover, tests have to show that there is enough viable heart muscle for restored blood flow to make a difference. Another surgical approach is left ventricular reconstruction, which involves cutting away damaged tissue so that the ventricle returns to a more normal shape and therefore presumably pumps better.

Sometimes a heart is so badly damaged that no medications or surgery will help — short of replacing the heart with a transplant. Transplant techniques, and drugs to prevent tissue rejection, have improved considerably. The five-year survival rate for adult heart transplant patients is now about 70%.

Devices
A weak heart tends to beat irregularly. So in addition to taking many medications, many heart failure patients are also getting pacemakers to maintain a steady heartbeat, and implantable cardioverter defibrillators (ICDs) to shock the heart if it beats too slowly or chaotically. Newer models combine a pacemaker and ICD in one machine.

Research has shown that ICDs prolong the lives of patients at risk for serious cardiac arrhythmias. And clinical trials have demonstrated that the devices can improve symptoms and make it possible for people to exercise.

But there have been setbacks. In June 2005, Guidant Corp. recalled certain makes of its ICD after some devices short-circuited and failed to deliver a shock, so patients died. And some once-heralded approaches have flopped. Not long ago, there was a lot of excitement about a dual-chamber pacemaker that sent electrical pulses to both the right atrium and ventricle. The theory was that this device would help the heart beat in a more natural, coordinated way. But a 2002 study punched a hole in that theory when it found that patients with dual-chamber devices did worse than those who had a standard ICD. The problem, ironically, is that the dual-chamber pacing threw the beating of the right and left ventricles out of sync.

Now the hot topic is biventricular pacing, also called cardiac resynchronization therapy. A pacemaker sends electrical pulses to the left and right ventricles to make them beat in unison and, in theory, give the heart more pumping power. Several clinical trials of this technique have shown impressive results. There’s some hope that biventricular pacing may actually “remodel” heart muscle, so it becomes stronger. Still, in some studies, as many as 30% of patients don’t benefit, so the device remains an expensive gamble. And the procedure itself is tricky: In one important trial, the doctors couldn’t get the device installed 12% of the time.

The upshot
Heart failure is still a tough customer. Even with all the advances, the mortality figures are sobering. About a fifth of patients die within a year of diagnosis, and half within five years. Still, the gains have been substantial, and they’re likely to continue. Heart failure patients — and their physicians — have more options and greater flexibility than ever before. It has become a condition that people can live with.

This article is provided courtesy of Harvard Medical International.
© 2005 President and Fellows of Harvard College||**||

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