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For the chapter in the Wells Handbook, please go to Chapter 9. Heart Failure.



  • image 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.

  • image 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), resulting in vasoconstriction and sodium and water retention as well as ventricular hypertrophy/remodeling. These compensatory mechanisms are responsible for the symptoms of HFrEF and contribute to disease progression.

  • image Our current understanding of HFrEF pathophysiology is best described by the neurohormonal model. Activation of endogenous neurohormones including norepinephrine (NE), angiotensin II, aldosterone, vasopressin, and numerous proinflammatory cytokines plays an important role in ventricular remodeling and the subsequent progression of HF. Importantly, pharmacotherapy targeted at antagonizing this neurohormonal activation has slowed the progression of HFrEF and improved survival.

  • image Most patients with HFrEF should be routinely treated with guideline directed medical therapy (GDMT) that includes an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a β-blocker. Selected patients should also receive loop diuretics, hydralazine/nitrates, or aldosterone antagonists. The benefits of these medications on slowing HF progression, reducing morbidity and mortality, and/or improving symptoms are clearly established.

  • image 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. When ACE inhibitors are contraindicated or not tolerated, an ARB or the combination of hydralazine and isosorbide dinitrate is a reasonable alternative. Patients with asymptomatic left ventricular dysfunction and/or a previous myocardial infarction (MI) (Stage B of the American College of Cardiology [ACC]/American Heart Association [AHA] classification scheme) should also receive ACE inhibitors, with the goal of preventing symptomatic HF and reducing mortality.

  • image The β-blockers carvedilol, metoprolol succinate, and bisoprolol have been shown to prolong survival, decrease hospitalizations and need for transplantation, and cause “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.

  • image Although chronic loop diuretic therapy frequently is used in patients with either 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 ...

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