Question:

A 63-year-old man with hypertension comes to the clinic for follow-up. He was last seen a year ago and has been maintained on amlodipine for the past 3 years. The patient has no symptoms and describes good exercise tolerance. He takes rosuvastatin for hyperlipidemia. The patient does not use tobacco, alcohol, or illicit drugs. Blood pressure is 132/78 mm Hg, and pulse is 82/min and regular. Oxygen saturation is 99%. Examination reveals a 2/6 ejection-type systolic murmur at the right second intercostal space. The patient's lungs are clear, and there is no peripheral edema. ECG shows normal sinus rhythm with nonspecific T wave abnormalities. He is referred for an echocardiogram, which reveals mild aortic sclerosis and left ventricular dilation with an ejection fraction of 35%. There are no regional wall motion abnormalities. Cardiac stress test is negative for ischemia. Which of the following is the best management for this patient?

Initiate angiotensin system inhibitor

Initiate digoxin

Initiate low-dose diuretic

Initiate spironolactone

Reassure and follow up in 6 months

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Pharmacotherapy for chronic heart failure with reduced ejection fraction
	Medication	Indication	Notes
Initial optimized therapy	Angiotensin receptor-neprilysin inhibitor*	NYHA classes I-IV with LVEF ≤40%	Slows disease progression & improves mortality
	Beta blocker	NYHA classes I-IV with LVEF ≤40%	Metoprolol succinate, carvedilol, or bisoprolol Reduces hospitalization & improves mortality
	Diuretics	NYHA classes II-IV with volume overload	Loop diuretic ± metolazone Improves symptoms & reduces hospitalization
Step 2 of optimized therapy	Aldosterone antagonist	NYHA classes II-IV with LVEF ≤35%	Reduces hospitalization & improves mortality
Step 3 of optimized therapy	SGLT-2 inhibitor	NYHA classes II-IV	Reduces symptoms & improves mortality
Supplementary agents	Isosorbide dinitrate + hydralazine	Angiotensin system blocker intolerance	Improves symptoms & may improve mortality
Supplementary agents	Digoxin	Persistent symptoms despite other therapy	Reduces hospitalization but no mortality benefit
Other angiotensin system blockers (ie, ACE inhibitor or angiotensin receptor blocker) are alternatives. LVEF* = left ventricular ejection fraction; NYHA = New York Heart Association; SGLT-2 = sodium-glucose cotransporter 2.

This patient has asymptomatic left ventricular systolic dysfunction (LVSD), which is typically diagnosed when echocardiography is performed to investigate an abnormal ECG or physical examination finding (eg, cardiac murmur due to aortic sclerosis). In the absence of evidence of coronary artery disease (ie, negative stress test), he most likely has dilated cardiomyopathy that is either idiopathic or secondary to chronic hypertension.

Asymptomatic LVSD is consistent with New York Heart Association (NYHA) class I heart failure. Per guidelines, all patients with asymptomatic LVSD (ie, ejection fraction ≤40%) should be initiated on an angiotensin system inhibitor (eg, ACE inhibitor), as these drugs have been shown to delay the onset of symptomatic heart failure and improve long-term cardiac morbidity and mortality.

Once a suitable dose has been achieved without hypotension, a beta blocker (eg, metoprolol) should also be added due to evidence of similar benefits in patients with asymptomatic LVSD. In this patient in particular, amlodipine should be discontinued in favor of maximizing angiotensin system inhibitor and beta blocker dosages.

(Choice B) Digoxin is a supplementary agent that can improve symptoms and reduce the rate of hospitalization in patients with symptomatic LVSD. However, it does not play a role in the management of asymptomatic LVSD.

(Choice C) Diuretics are useful for symptomatic relief (eg, lower extremity edema, dyspnea) in patients with symptomatic heart failure (ie, NYHA class II, III, or IV) and evidence of volume overload. However, these drugs may cause dehydration in patients with asymptomatic LVSD and are generally not indicated.

(Choice D) Mineralocorticoid receptor antagonists (eg, spironolactone) have been shown to improve mortality in patients with LVSD and are recommended in patients with LVSD and persistent symptoms despite therapy with an angiotensin system inhibitor and a beta blocker. However, they are not indicated in patients with asymptomatic LVSD.

(Choice E) Reassurance and routine follow-up alone are not appropriate. This patient should be started on an angiotensin system inhibitor and beta blocker to delay the onset of heart failure symptoms and improve long-term mortality.

Educational objective:
An angiotensin system inhibitor (eg, ACE inhibitor) is first-line therapy in patients with asymptomatic left ventricular systolic dysfunction as it delays onset of heart failure symptoms and improves cardiac morbidity and mortality. A beta blocker should also be added once a suitable angiotensin system inhibitor dose is established.