Patients With Left Ventricular Dysfunction With Current or Prior Symptoms (Stage C)

General Measures

Measures listed as class I recommendations for patients in stages A or B are also appropriate for patients with current or prior symptoms of HF. In addition, moderate sodium restriction, along with daily measurement of weight, is indicated to permit effective use of lower and safer doses of diuretics, even if overt sodium retention can be controlled by the use of diuretics.¹

Immunization with influenza and pneumococcal vaccines may reduce the risk of respiratory infection. While most patients should not participate in heavy labor or exhaustive sports, physical activity should be encouraged, except during periods of acute decompensation or in patients with suspected myocarditis, because restriction or activity promotes physical deconditioning, which may adversely affect clinical status and contribute to the exercise intolerance of patients with HF.¹

Three classes of drugs can exacerbate the syndrome of HF and should be avoided in most patients:¹

• Antiarrhythmic agents can exert important cardiodepressant and proarrhythmic effects.
  
• Calcium channel blockers can lead to worsening HF and have been associated with an increased risk of cardiovascular events.
  
• Nonsteroidal anti-inflammatory drugs can cause sodium retention and peripheral vasoconstriction and can attenuate the efficacy, and enhance the toxicity, of diuretics and ACE inhibitors.

Patients with HF should be monitored closely for changes in serum potassium and every effort should be made to prevent the occurrence of either hypokalemia or hyperkalemia, both of which may adversely affect cardiac excitability and conduction and may lead to sudden death.¹

Noncompliance with diet and medications can rapidly and profoundly affect the clinical status of patients and increases in body weight and minor changes in symptoms commonly precede by several days the occurrence of major clinical episodes that require emergency care or hospitalization. Patient education and close supervision, which includes surveillance by the patient and his or her family, can reduce the likelihood of noncompliance and lead to the detection of changes in body weight or clinical status early enough to allow the patient or a healthcare provider an opportunity to institute treatments that can prevent clinical deterioration.¹

Drugs Recommended for Routine Use

Most patients with HF should be routinely managed with a combination of four types of drugs:¹

• Diuretics interfere with the sodium retention of HF by inhibiting the reabsorption of sodium or chloride at specific sites in the renal tubules.¹ Diuretics are essential for the symptomatic treatment when fluid overload is present and manifests as pulmonary congestion or peripheral edema. The use of diuretics may result in rapid improvement of dyspnea and increased exercise tolerance.²
  
• Angiotensin Converting Enzyme (ACE) Inhibitors interfere with the renin-angiotensin system by inhibiting the enzyme responsible for the conversion of angiotensin I to angiotensin II, but it is not clear whether the effects of ACE inhibitors can be explained solely by the suppression of angiotensin II. ACE inhibition not only interferes with the renin-angiotensin system, but also enhances the action of kinins and augments kinin-mediated prostaglandin and kinin potentiation may be as important as angiotensin suppression in mediating the effects of ACE inhibitors.¹
  
• Beta-Andrenergic Receptor Blockers act principally to inhibit the adverse effects of the sympathetic nervous system in patients with HF. While cardiac andrenergic drive initially supports the performance of the failing heart, long-term activation of the sympathetic nervous system exerts deleterious effects that can be antagonized by the use of beta-blockers.¹
  
  Beta-blocking agents are recommended for the treatment of all patients with stable, mild, moderate and severe heart failure from ischemic or nonischemic cardiomyopathies and reduced left ventricular ejection fraction, in NYHA class II to IV or standard treatment, including diuretics and ACE inhibitors unless there is a contraindication.²
  
• Digitalis Glycosides exert their effects in patients with HF through their ability to inhibit sodium-potassium adenosine triphosphatase (ATPase). Inhibition of this enzyme in cardiac cells results in an increase in the contractile state of the heart, and for many decades, the benefits of digitalis in HF were ascribed exclusively to this positive inotropic action. However, recent evidence suggests that the benefits of digitalis may be related in part to enzyme inhibition in noncardiac tissues. These observations have led to the hypothesis that digitalis acts not as a positive inotropic drug, but primarily by attenuating the activation of neurohormonal systems (e.g., inhibition of sodium-potassium ATPase in vagal afferent fibers acts to sensitize cardiac baroreceptors, which in turn reduces sympathetic outflow from the central nervous system).¹

Interventions to be Considered for Use in Selected Patients

Controlled clinical trials have shown some interventions to be useful in a limited cohort of patients with HF. Several of these agents are undergoing active investigation in large-scale trials to determine whether their role in the management of HF might be justifiably expanded.1

• Aldosterone Antagonists— Although short-term therapy with both ACE inhibitors and angiotensin II receptor antagonists can lower circulating levels of aldostrone, it is not clear that such suppression is sustained during long-term treatment. The lack of long-term suppression may be important, because some data suggest that aldosterone may exert adverse effects on the structure and function of the heart, independently of and in addition to the deleterious effects produced by angiotensin II.¹
  
  Spironolactone is the only aldosterone antagonist available for clinical use in the United States. In a large-scale, long-term trial, the addition of low doses of spironolactone to therapy for patients with recent or current class IV symptoms who were taking an ACE inhibitor reduced the risk of death and hospitalization. The most marked effects were seen in patient who were also given digitalis and beta-blockers.¹
  
  The addition of low doses of spironolactone should be considered in patients with recent or current symptoms at rest despite the use of digoxin, diurectics, an ACE inhibitor and (usually) a beta-blocker.¹
  
  Aldosterone antagonism is recommended in advanced heart failure (NYHA III-IV), in addition to ACE inhibition and diuretics to improve survival and morbidity.²
  
• Angiotensin Receptor Blockers (ARBs)— An alternative approach to inhibiting the actions of angiotensin II in patients with HF is the use of drugs that block the angiotensin II receptor. These agents were developed on the premise that interference with the renin-angiotensin system (without inhibition of kininase) would produce all of the benefits of ACE inhibitors, while minimizing the risk of adverse reactions. However, it is now known that many of the side effects of ACE inhibitors in HF are related to the suppression of angiotensin II formation, whereas some of the benefits may be related to the accumulation of kinins.¹
  
  Angiotensin receptor blockers should not be considered equivalent or superior to ACE inhibitors in the treatment of HF. Thus, they should not be used for the treatment of HF in patients who have no prior use of an ACE inhibitor and should not be substituted for ACE inhibitors in patients who are tolerating ACE inhibitors without difficulty.¹
  
• Hydralazine and Isosorbide Dinitrate— Although isosorbide dinitrate and hydralazine were initially combined because of their complementary dilating actions on peripheral blood vessels, recent evidence suggests that hydralazine and isosorbide dinitrate may also act at a biochemical and genetic level. Nitrates can inhibit abnormal myocardial and vascular growth and may, thereby, attenuate the process of ventricular remodeling. Theoretically, hydralazine may interfere with the biochemical and molecular mechanisms responsible for the progression of HF, as well as the development of nitrate tolerance.¹
  
  The combination of hydralazine and isosorbide dinitrate should not be used for the treatment of HF in patients who have no prior use of an ACE inhibitor and should not be substituted for ACE inhibitors in patients who are tolerating ACE inhibitors without difficulty.¹
  
• Exercise Training— Historically, HF patients were advised to avoid physical exertion in the hope that bed rest might minimize symptoms and in the belief that physical activity might accelerate the progression of left ventricular dysfunction. However, it is now understood that a reduction in physical activity leads to a state of physical deconditioning that contributes to the symptoms and exercise intolerance of patients with chronic HF. Limitations of activity may not only impair exercise capacity, but may also produce adverse psychological effects and impair peripheral vasodilatory responses. These findings have led to the hypothesis that exercise training might improve the clinical status of patients with chronic HF.¹

For more information on treating specific stages of heart failure, click on the following topics:

Patients at High Risk for Developing Left Ventricular Dysfunction (Stage A)
Patients with Left Ventricular Dysfunction Who Have Not Developed Symptoms (Stage B)
Patients With Left Ventricular Dysfunction With Current or Prior Symptoms (Stage C)
Patients with Refractory End-Stage HF (Stage D)

References