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Clinical management of patients with heart failure (HF) varies widely based on the clinical phenotype at presentation. Those in the earliest stage of disease with asymptomatic ventricular dysfunction (American College of Cardiology [ACC]/American Heart Association [AHA] stage B) may be amenable to treatment with neurohormonal antagonists, including angiotensin-converting inhibitors and β-adrenergic receptor antagonists, with the goal of facilitating ventricular recovery and preventing the development of clinical HF (not further discussed). Those with symptomatic HF (ACC/AHA stage C) comprise a heterogeneous group in whom the approach to therapy is differentiated largely based on measurement of the left ventricular ejection fraction. Data from prospective, randomized clinical outcomes trials enrolling patients with symptomatic chronic HF and reduced ejection fraction (HFrEF) has provided a rich evidence base that supports the efficacy of stepped pharmacologic therapy with neurohormonal antagonists, including renin-angiotensin-aldosterone system (RAAS) antagonists, neprilysin inhibitors, β-adrenergic receptor antagonists, and mineralocorticoid receptor antagonists, as a complement to device-based treatment with cardiac resynchronization therapy and implantable cardioverter-defibrillators. By contrast, treatment of patients with symptomatic chronic HF and preserved ejection fraction (HFpEF) has remained heavily symptom-focused owing to the lack of evidence to support specific pharmacologic therapies to modify disease progression. Even with effective therapy, patients with both HFrEF and HFpEF are at risk for clinical deterioration, typically as a consequence of progressive sodium and fluid retention that fuels the development of congestive symptoms and acute decompensated HF (ADHF). Management of these exacerbations (frequently hospital-based) is heavily focused on hemodynamic stabilization, decongestion, and institution of appropriate disease-modifying therapy in the transition back to chronic ambulatory management. Recurrent episodes of ADHF despite careful longitudinal follow-up and effective treatment may signal the onset of an advanced or refractory HF phenotype (ACC/AHA stage D) in which the risk of mortality from sudden death or end-stage HF is high, and consideration of salvage therapies including cardiac transplant or mechanical circulatory support may be appropriate prior to escalation of palliative measures (Chap. 260).



Although clinical trials of renin-angiotensin-aldosterone antagonists, digoxin, β-adrenergic receptor blockers, and neprilysin inhibitors have been conducted in patients with HFpEF, none has conclusively demonstrated a mortality reduction. In the absence of specific pharmacologic therapies proven to improve clinical outcomes, management of patients with HFpEF is therefore focused on improving symptoms and effort tolerance through lifestyle modification, control of congestion, stabilization of heart rhythm (particularly in those with atrial fibrillation), control of blood pressure to guideline-recommended targets, and management of comorbidities that may contribute to disease progression (including, for example, obesity, obstructive lung disease, obstructive sleep apnea, diabetes/insulin resistance, anemia, iron deficiency, and chronic kidney disease).


Attempts to export the benefits of drugs that improve clinical outcomes in patients with HFrEF, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-adrenergic receptor blockers, digoxin, and mineralocorticoid receptor ...

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