Friday, July 25, 2008

Heart Failure and Medical Drugs Treatment

Introduction

Once thought of as a terminal condition, patients today are living for years even decades with heart failure, thanks in large part to medications. Nonetheless, prevention remains the key.

What is it?

Heart failure, also called left ventricular dysfunction, is a condition in which the heart muscle does not pump adequately. As a result, blood is not dispersed adequately to the body and fluid backs up into the lungs, causing "congestion.

In some patients, heart failure occurs suddenly, while in other cases it develops gradually. As heart function deteriorates over the years, the strength of muscle contractions may be reduced. In other cases, mechanical problems may affect the ability of heart chambers to fill with blood, so that less blood is pumped out to tissues in the body. In other cases, the pumping chambers enlarge and fill with too much blood. The weakened heart muscle may not be strong enough to pump out all of the blood it receives. There are also cases where the heart enlargement affects the functioning of the valves that usually stop blood from flowing backwards into the heart chamber it just left. This condition, called regurgitation, may make the heart failure even worse.

When the heart cannot efficiently pump blood into the arteries, the blood backs up into the lungs and the resulting fluid collection is responsible for the congestion and breathing difficulties. Blood may also collect in veins, especially in the lower extremities, and cannot circulate into tissues.

In most patients, heart failure is controllable. With appropriate care, people may live for many years after the diagnosis is made.

What causes it?

Heart failure (HF) is often the direct result of the heart muscle's inability to contract with enough force to pump blood efficiently. Among the causes of HF are heart valve disease, scar tissue left from a previous heart attack, and high blood pressure which has been uncontrolled for long periods.

Coronary artery disease, in which the coronary arteries supplying the heart muscle are narrowed by plaques (usually from high cholesterol), is the most common cause of HF accounting for 60% of people with the disease. Although coronary artery disease often starts at an early age, HF occurs most often in the elderly. The majority of these patients are women. Researchers theorize that this is probably because men are more likely to die from coronary artery disease before it progresses to HF.

HF is also associated with alcohol abuse and drug abuse, particularly cocaine and amphetamines, which affect heart rate. Among other disorders that can cause HF are hyperthyroidism (or an overactive thyroid), HIV/AIDS, treatment of cancer (such as radiation and certain chemotherapy agents), and various abnormalities of the heart valves. In addition, viral infection or inflammation of the heart, known as myocarditis, or a heart muscle disease called cardiomyopathy can cause HF. There are also rare cases where HF is caused by extreme vitamin deficiencies.

Who has it?

Over 5 million Americans have chronic HF, with 550,000 new cases occurring each year. HF results in almost 1 million hospitalizations each year and is the most common diagnosis among patients between the ages of 55 to 65 years discharged from hospitals.

Forty four percent of patients with HF have diabetes, 30% have kidney problems, 52% are women, and atrial fibrillation (irregular heart rhythm) accounts for approximately 31% of heart failure patients. These numbers are expected to continue to increase as the population of elderly Americans rises.

What are the risk factors?

Risk factors are characteristics that may increase your chance for developing a condition. If you have conditions such as coronary artery disease, valvular heart disease, diabetes or high blood pressure, then you are at risk for developing heart failure (HF). Coronary artery disease, high blood pressure, and diabetes are the leading causes of heart failure. Other factors that increase your chance of having or developing HF include:

  • Age - Older people are more likely to develop HF than younger people.
  • Male gender - Before age 60 or 70, men are more likely than women to develop coronary disease.
  • Family history of heart disease
  • Cigarette smoking
  • High blood pressure
  • Diabetes
  • Alcohol abuse
  • Coronary artery disease
  • Chronic kidney disease
  • Atrial fibrillation
  • High cholesterol
  • COPD (lung disease) or asthma
  • Race:African Americans are more likely to develop heart failure than Caucasians

What are the symptoms?

Due to the complexity of trying to determine whether or not a symptom is caused by the inadequate forward flow of blood or the backward buildup of blood, the following list of symptoms are all attributed to heart failure.

Common symptoms include:

  • Exercise intolerance (diminished ability to perform physical tasks)
  • Cough
  • Fatigue
  • Nocturia (having to go to the bathroom frequently during the night)
  • Abdominal pain
  • Loss of appetite
  • Nausea
  • Bloating
  • Mental status change such as confusion
  • Shortness of breath (that may even occur at rest)
  • Cool or pale extremities (legs, feet, hands, fingers)
  • Edema (or swelling), particularly in the lower legs, ankles, and feet
  • Chest pain

How is it treated?

The management of heart failure (HF) depends on its cause and clinical course. Since high blood pressure, coronary artery disease, high cholesterol, and valvular heart disease are common causes of HF, aggressive management of these conditions is essential. Treatment goals include:

  • Improve the individual's quality of life and symptoms
  • Prevent the heart failure from worsening
  • Prolong the individual?s life span
  • Treat the underlying cause of the heart failure.

When a person is diagnosed with HF, both non-drug (described in "Helping Yourself") and drug therapy is recommended. All patients with chronic HF due to left ventricle systolic dysfunction (means the heart muscle itself is weakened and not able to pump blood out of the heart as effectively as before) should receive an angiotensin-converting enzyme inhibitor (ACE-Inhibitor), unless the person is intolerant to or has a contraindication to the use of this class of drugs. ACE-Inhibitors are "vasodilators," which cause the peripheral blood vessels to dilate, or open up. This reduces the work of the heart by making it easier for blood to flow.

ACE-Inhibitors should even be used in HF patients who do not yet have symptoms of HF because these drugs have been shown in clinical studies to reduce the risk of disease progression and improve patient survival. In patients with fluid retention, ACE-Inhibitors are typically combined with diuretics.

Diuretics (aka, "water pills"), available since the 1950s, are used to help the kidneys get rid of excess water and sodium, thereby reducing blood volume and the heart's workload. These drugs can help alleviate HF symptoms like shortness of breath and lower extremity edema (fluid collection in the feet, ankles, & lower legs).

Patients who cannot tolerate ACE-Inhibitors should be treated with angiotensin II receptor blockers (ARBs). ARBs have been shown to improve survival in persons who have HF.

There may be special situations when a combination of an ACE-Inhibitor and ARB may be used. However, the role of this combination is not well-defined and is somewhat controversial.

Other "vasodilators" such as a combination of hydralazine plus nitrate therapy may be used if patients cannot tolerate either ACE-Inhibitors or ARBs. The hydralazine and nitrate combination is considered a second-line therapy and should not be used for the treatment of HF in patients who have not been previously treated with an ACE-Inhibitor. A newer drug called BiDil combines hydralazine and isosorbide dinitrate into one tablet. BiDil was shown in one study to improve survival in African American persons who have HF.

Beta-blockers are also a first-line recommendation for HF patients. These drugs decrease the heart rate as well as the overall work of the heart through vasodilation. Certain beta-blockers have been shown in clinical studies to reduce the risk of death associated with HF. All persons with stable, mild-to-moderate or moderate-to-severe HF due to left ventricular dysfunction (who do not have intolerance or contraindications) should have a beta-blocker (either bisoprolol, carvedilol, or metoprolol succinate) added to a regimen of an ACE-Inhibitor and a diuretic as early as possible.

Some clinicians recommend using digitalis (digoxin), a drug that has been used since the 18th century, to strengthen the heart's pumping action. Other clinicians contend that digitalis has not been shown to affect the normal course of HF. They recommend that it should be reserved for patients who still have symptoms of HF after being treated with an ACE-Inhibitor, diuretic, and a beta-blocker or for those patients who also have atrial fibrillation. While digoxin has not been adequately shown in clinical studies to reduce death from HF, it has been shown to improve HF symptoms and patient quality of life. Patients taking both diuretics and digitalis may need to supplement their levels of potassium.

In patients with severe heart failure, another type of diuretic can be added to treatment regimens consisting of an ACE-Inhibitor, diuretic, beta-blocker, and digoxin. Spironolactone (brand name: Aldactone), a potassium-sparing diuretic, has been shown in clinical studies to reduce mortality in patients with severe heart failure and thus, may be considered for use in these patients. Spironolactone blocks the action of aldosterone, a hormone that may exert adverse effects on the heart muscle and peripheral blood vessels. Spironolactone not only may improve fluid balance but may also decrease the risk of progression of HF. For patients with more severe forms of HF, spironolactone has been shown in clinical studies to reduce hospitalizations and death from heart failure. Spironolactone's efficacy and safety in patients with mild to moderate HF remains unknown.

Most recently, eplerenone (Inspra) received FDA approval for the treatment of heart failure that occurs following a heart attack. Eplerenone is a selective aldosterone receptor blocker, the first drug in this class. Individuals may be candidates for eplerenone therapy if they have documented heart failure proceeding a heart attack. For more information on the use of eplerenone following a heart attack, talk to your doctor or primary health care provider.

Sometimes, surgery proves effective. When HF is due to disease of the heart valves, surgery to repair the valve or implant an artificial heart valve may be helpful. Surgery is also used to correct congenital heart defects that can lead to HF. When HF is caused by partial or complete blockage of the coronary arteries, coronary bypass surgery or angioplasty may be used.

Heart transplants are a last resort in treating severe HF caused by diseased heart muscle. Although the success rate of heart transplants has significantly improved, the cost of the operation and shortage of donor organs makes it impractical except as a last resort.

Drug classes used to treat Heart Failure

  • ACE-Inhibitors
  • Aldosterone Receptor Blockers
  • Angiotensin II Receptor Blockers
  • Beta Blockers
  • Cardiac Glycosides
  • Diuretics
  • Nitrate and Peripheral Vasodilator Combination
  • Nitrates
  • Peripheral Vasodilators
  • Selective Aldosterone Receptor Antagonist

What is on the horizon?

Heart transplantation has become a widely used treatment of end-stage congestive heart failure. While the goal of treatment of HF is to avoid the need for transplantation, advances in the care of patients with heart transplants will make this a viable option for more people in the future.

Many drugs are being developed for heart failure. These drugs are currently undergoing clinical trials to see how effective they will be for heart failure, including carvedilol controlled-release.

Conivaptan and tolvaptan are two new drugs currently being studied for use in heart failure. These are vasopressin antagonists that may help rid the body of excess fluid to help relieve the "congestion" commonly seen in HF.

A new drug Bystolic, generic name is nebivolol, is being studied for a possible indication for heart failure. It is a beta-1 specific blocker. Similar to other beta blockers it works to reduce the force and rate of the heartbeat and decrease muscular tone in blood vessels. Also like other beta blockers, it can produce nitric oxide which will cause vasodilation thereby allowing blood to flow more freely. It is being studied because unlike other beta blockers it retains its beta specific action at higher doses which would equate to less side effects. A clinical trial comparing nebivolol to other beta blockers that are approved for the treatment of heart failure is currently underway.

Natriuretic peptides are being studied to see if they help urine output when combined with a commonly used diuretic called furosemide. The benefit will be that these two medications will be able to remove more fluid from the body resulting in less "congestion" which can make heart failure worse. Clinical studies are being performed to evaluate the effects of these medications together.

A process known as cardiac resynchronization is currently being studied for patients with heart failure. This process uses electrical stimulation to get the heart to pump better with a pacemaker. The long term effects are not yet known, but it is currently being evaluated to see if this process will be useful to heart failure patients.

Another process known as ultra-filtration is being studied to see if this process will help reduce fluid overload, thus reducing future hospitalizations and emergency room visits. This process is also known as kidney (renal) replacement therapy and is used experimentally in those individuals who have severe heart failure.