Heart failure (HF) is a progressive clinical syndrome that can result from any changes in cardiac structure or function that impair the ability of the ventricle to fill with or eject blood. HF may be caused by an abnormality in systolic function, diastolic function, or both. The leading causes of HF are coronary artery disease and hypertension. The primary manifestations of the syndrome are dyspnea, fatigue, and fluid retention.
In heart failure with reduced ejection fraction (HFrEF), there is a decrease in cardiac output resulting in activation of a number of compensatory responses that attempt to maintain adequate cardiac output. These responses include activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). These compensatory mechanisms are responsible for the symptoms of HFrEF and contribute to disease progression.
Our current understanding of HFrEF pathophysiology is best described by the neurohormonal model. Activation of endogenous neurohormones including norepinephrine, angiotensin II, aldosterone, vasopressin, and numerous proinflammatory cytokines play an important role in ventricular remodeling and the subsequent progression of HF. Importantly, pharmacotherapy targeted at antagonizing this neurohormonal activation slows the progression of HFrEF and improves survival.
Most patients with HFrEF should be routinely treated with guideline-directed medical therapy (GDMT) that includes an angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or angiotensin II blocker/neprilysin inhibitor and an evidence-based β-blocker. Selected patients should also receive aldosterone antagonists, loop diuretics, or hydralazine/nitrates. The benefits of these medications on slowing HF progression, reducing morbidity and mortality, and/or improving symptoms are clearly established.
In patients with HFrEF, ACE inhibitors improve survival, slow disease progression, reduce hospitalizations, and improve quality of life. The doses for these agents should be targeted at those shown in clinical trials to improve survival. ARBs are recommended for patients intolerant to ACE inhibitors due to angioedema or cough. In symptomatic patients receiving an ACE inhibitor or ARB, replacement with the combination ARB/neprilysin inhibitor is recommended.
The β-blockers carvedilol, metoprolol succinate, and bisoprolol prolong survival, decrease hospitalizations and need for transplantation, and promote “reverse remodeling” of the left ventricle. These agents are recommended for all patients with HFrEF unless contraindicated. Therapy must be instituted at low doses, with slow upward titration to the target dose.
Although chronic loop diuretic therapy frequently is used in patients with HFrEF or HFpEF, it is not mandatory. Diuretic therapy along with sodium restriction is required only in those patients with peripheral edema and/or pulmonary congestion. Many patients will need continued diuretic therapy to maintain euvolemia after fluid overload is resolved.
Aldosterone antagonists reduce mortality in patients with HFrEF and New York Heart Association (NYHA) class II to IV symptoms and thus should be strongly considered in these patients provided that potassium and renal function can be carefully monitored. Aldosterone antagonists may be considered to reduce the risk of hospitalization in patients with HFpEF.
The combination of hydralazine and nitrates improves the composite endpoint of mortality, hospitalizations for HF, and quality of life in ...