Initial Drug Treatment - Systolic Dysfunction

The initial drug treatment of significant systolic dysfunction typically includes: (1) renin-angiotensin system antagonists (either an angiotensin receptor-neprilysin inhibitor (ARNI), an angiotensin converting enzyme inhibitor (ACEI), or a single agent angiotensin II receptor blocker (ARB), (2) beta blockers and (3) diuretics.

Renin-angiotensin system antagonists are vasodilators that decrease both preload and afterload. They improve survival and exercise capability and inhibit the process of remodeling. Angiotensin receptor-neprilysin inhibitors (ARNI) are now considered first-line in this class due to superior effects on survival when compared to ACE inhibitors. Neprilysin inhibition increases circulating natriuretic peptides, further promoting diuresis and vasodilation and improving cardiac remodeling. Those patients unable to tolerate ARNI should be started instead on an ACE inhibitor.

An alternative approach for patients who cannot tolerate ACE inhibitors is the use of angiotensin II receptor blockers (ARB). Unlike ACE inhibitors, they do not inhibit kinase and, therefore, are not associated with cough, a common side effect of ACE inhibitors.

Beta blockers block cardiac adreno-receptors and improve ejection fraction through upregulation of adreno-receptors. They improve survival, reduce hospitalizations and improve symptoms. Beta blocker therapy should be cautiously administered after control of the patient's volume status. These agents may initially cause decompensation and should be started at a very low dose. They should be progressively titrated upward to a target dose.

Diuretics decrease preload. They do not improve survival but are helpful in managing symptoms related to congestion.

Efforts should be made to optimize therapy with additional agents that are known to reduce mortality, in eligible patients.

Mineralocorticoid Receptor Antagonists (MRA) reduce hospitalization and death in class II-IV patients already on standard therapy including beta blockers.

The combination of hydralazine and isosorbide dinitrate provides complementary vasodilating effects in patients who cannot tolerate ACE inhibitors or ARBs. The combination may have an added benefit to ACE inhibitors and ARBs in some patients of African descent.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i), initially developed as blood glucose lowering drugs for type 2 diabetes, reduce mortality in patients with heart failure with reduced ejection fraction (HFREF), regardless of diabetic status.

Secondary therapies may be helpful in selected patients.

Ivabradine is indicated for HFREF patients and a resting heart rate ≥70 (on maximum beta blockers) and reduces hospitalizations for heart failure.

Digitalis improves symptoms without influencing mortality in patients with elevated filling pressures, or volume overload. Digitalis should be used in low doses, to keep digitalis levels less than one nanogram per milliliter.

Exercise training should be considered for all stable patients on standard drug therapy, because it can lessen symptoms, increase exercise capacity, and improve the quality of life.

More intensive therapy for hospitalized patients with refractory congestive heart failure includes the temporary use of intravenous agents. These may provide further afterload reduction with or without preload reduction and include IV nitroglycerin and nitroprusside. Alternatively, intravenous inotropic drugs may be used to temporarily increase the contractility of the left ventricle and include dobutamine and milrinone.

Biventricular pacing can improve functional capacity, quality of life and survival in selected patients.