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Heart Failure

Conventional Treatment of Heart Failure

In 2013, a report was developed by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA). In addition to making specific recommendations for subgroups of heart failure patients, this report introduced the concept of “guideline-directed medical therapy,” which proposes a combination of drugs and lifestyle changes that enable physicians to define the best treatment course for individual patients with heart failure (Yancy 2013).
Clinical practice guidelines for the treatment of acute and chronic heart failure have been proposed by several cardiology societies (McKelvie 2013; Hunt 2009; McMurray 2012; Krum 2011); most recommendations have parity between the different organizations. According to the ACCF/AHA guidelines, treatment recommendations are stratified by disease progression.

Treatment Considerations for Patients at Risk for Heart Failure (ACCF/AHA stage A or B)

For patients at risk for heart failure (ACCF/AHA Stage A or B), the panel recommends lifestyle modifications (smoking cessation, increased exercise, reductions in alcohol consumption) as well as the treatment of high blood pressure and metabolic disorders (diabetes, lipid disorders) (Hunt 2009).

Medications. Medications that may be used in patients at risk of heart failure include:

  • Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors (eg, enalapril [Vasotec®], lisinopril [Zestril®]) restrict the activity of ACE, the enzyme that catalyzes the final step in the synthesis of the hypertensive hormone angiotensin II. By lowering the levels of angiotensin II, ACE inhibitors promote the dilation of blood vessels and increase the excretion of water and sodium from the kidneys, lowering blood volume. In clinical trials of patients with heart failure, ACE inhibitors have significantly reduced mortality by 20-23% and the risk of hospitalization for heart failure by 33% (Ascenção 2008). Although they are generally well-tolerated in most individuals, side effects may include cough, skin rash, low blood pressure, dizziness, weakness, headache, elevated potassium, impotence, and low zinc levels (Parish 1992; Agustí 2003; Dunn 2009).
  • Angiotensin receptor blockers (ARBs). ARBs (eg, candesartan [Atacand®], valsartan [Diovan®]) are a newer class of drugs that also interfere with the activity of angiotensin by blocking its interaction with target cells. This approach was thought to result in more effective inhibition of angiotensin II activity and better patient tolerability (Eisenberg 2006), although to date ARBs have not shown the same robust effect on reducing cardiovascular mortality in clinical trials as ACE inhibitors (Heran 2012). Side effects include low blood pressure, dizziness, weakness, fatigue, abdominal pain, headache, nausea, and breathing or swallowing difficulties (Barreras 2003; Kyrmizakis 2004; Terra 2003; Mayo Clinic 2011).
  • Beta blockers. Beta blockers (eg, carvedilol [Coreg®], bisoprolol [Zebeta®], metoprolol [Lopressor®]) lower heart rate and blood pressure by blocking β-adrenoceptors (Bakris 2006). Normally, adrenoceptors sense the hormones epinephrine and norepinephrine that are in the blood or secreted from nerves and respond by increasing the heart rate. Beta blockers disrupt this interaction. Several drugs in this class improve the ejection fraction and survival in heart failure patients (Klapholz 2009; Chatterjee 2013). Side effects include hyperglycemia, low blood pressure, dizziness, weakness, headache, nausea/vomiting, vision changes, difficulty breathing or swallowing, weight gain, vivid or active dreams, depression, decreased sexual activity, and slow or irregular heartbeats (Frishman 1988; Dennis 1991; Ko 2004; Boxall 2012; WebMD 2012).

Treatment Considerations for Patients with Heart Failure (ACCF/AHA stage C or D)

For patients with heart failure (Stage C), the ACCF/AHA recommends the same lifestyle modifications as for at-risk patients, with the addition of dietary salt restriction. Drug therapy includes the routine use of ACE inhibitors/ARBs and beta blockers, with the addition of a diuretic (such as furosemide [Lasix®]) to address fluid retention, increase exercise tolerance, and improve survival (Faris 2012). Most patients will be managed by using a combination of all three of these drugs (Hiramitsu 2009). Stage D heart failure, which does not respond to the aforementioned therapies, may require extraordinary measures for treatment, such as the chronic administration of inotropic medications (drugs that increase the force of heart contraction, such as dobutamine [Dobutrex®]) (Coons 2011), heart transplantation, or permanent mechanical support (Hunt 2009). Additional therapies may be warranted in some patients, including:

  • Mineralocorticoid/aldosterone receptor antagonists (MRAs). MRAs (eg, spironolactone [Aldactone®]) inhibit the activity of the hormone aldosterone, which is produced by the adrenal glands and acts on the kidneys to increase the retention of sodium and water. Sodium and water retention play a role in the progression of heart failure. Several studies of MRAs have shown their ability to reduce mortality and hospitalization, and their strongest indication is for patients with stage C/D (NYHA class III/IV) heart failure who also present with reduced left ventricular function (Markowitz 2012). One side effect of spironolactone is testosterone reduction. This occurs because in addition to countering the effects of aldosterone, spironolactone reduces production of male sex hormones (androgens) and blocks their ability to activate their target, the androgen receptor (Rathnayake 2010). A newer aldosterone antagonist, eplerenone (Inspra®), may be a good alternative for those wishing to avoid the testosterone reduction associated with spironolactone as it does not block androgen signaling (Sanchez-Mas 2010).
  • Digoxin (Lanoxin®). Digoxin, derived from the plant Digitalis lanata (foxglove), has been used for over 200 years to treat cardiac problems and continues to be prescribed for chronic heart failure. It produces modest increases in the contractility of the heart and may alleviate some types of arrhythmia, but its high potential for toxicity under certain conditions in addition to the development of more effective compounds have reduced its overall usage in favor of less toxic drugs (Yang, Shah 2012). Digoxin toxicity can cause potentially serious heart rhythm irregularities and other symptoms such as vomiting, headache, and confusion. Since a number of variables such as kidney function and concomitant medications can influence metabolism of digoxin, dose standardization is difficult and individual patient monitoring is important to avoid toxicity (Lip 1993).
  • Medical devices. Patients who do not respond to drug therapy may benefit from implantable devices that control the contraction of the heart chambers and improve cardiac output. Cardiac resynchronization therapy (CRT) devices and implantable cardioverter defibrillators (ICDs) deploy electrical leads into the heart chambers to control contraction and help ensure the heart rhythm remains normal (Smith 2012). Replacement of a damaged or diseased heart valve with a mechanical valve can help stabilize heart function in cases where heart failure arises due to problems with a heart valve(s). Some patients at risk for heart failure (stage B) may also be eligible for an ICD or valve replacement. Left ventricular assist devices (LVADs) are implantable pumps that can help compensate for impaired left ventricular function in patients with severe heart failure who are either on a waiting list or are not eligible for heart transplantation. In fact, for some patients, LVADs can supplant the need for heart transplantation altogether (Carrel 2012). As technology continues to advance, the contribution of implantable devices to cardiac care is surely to expand along with an improving outlook for patients who can take advantage of these mechanical aids.