Treatment of Heart Failure With Normal Ejection Fraction

Heart failure (HF) is a major cause of mortality and morbidity and one of the most frequent reasons for hospital admission in the United States and Europe. Currently, more than 50% of HF patients have a normal (N) left ventricular (LV) ejection fraction (EF) (LVEF >50%). The main pathophysiologic processes involved in HFNEF are increased LV stiffness and abnormal relaxation, resulting in impaired LV filling. Hypertension and myocardial ischemia are the most common causes of HFNEF. Precipitating factors include volume overload, tachycardia, physical exercise, systemic stressors (such as fever and infection), arrhythmia, increased salt intake, and use of nonsteroidal anti-inflammatory drugs. There is little evidence to guide treatment, as previously HFNEF patients have been excluded from clinical trials on the basis of a normal LVEF. Survival improved over time in patients with reduced (R) EF (HFREF) (LVEF <40%), reflecting the beneficial effects of treatment in this phenotype. However, survival did not improve for HFNEF patients. The approach to the treatment of HFNEF patients should focus on reducing LV filling pressure, controlling hypertension, modifying ischemia, and improving LV relaxation. Therefore, diuretics are suitable for HFNEF patients to reduce ventricular filling pressure. Hypertension can be treated by using multiple agents if necessary. Drugs of particular interest and recommended to treat hypertension are calcium channel blockers (CCBs) and antagonists of the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. Ischemic heart disease can be treated with antiplatelet therapy, anticoagulants, and β-blockers. Heart rate control in atrial fibrillation can be achieved with β-blockers and digoxin. Finally, ACE inhibitors and ARBs could potentially decrease LV hypertrophy in hypertensive patients with HFNEF.