Cardiology · Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

USMLE2PANCE
7

Bets

The facts most likely to be tested

1

HFrEF is defined by an ejection fraction ≤ 40% and typically presents with systolic dysfunction and eccentric remodeling of the left ventricle.

Confidence:
2

The four pillars of guideline-directed medical therapy (GDMT) for HFrEF include ARNI (or ACEi/ARB), beta-blockers (specifically carvedilol, metoprolol succinate, or bisoprolol), MRA, and SGLT2 inhibitors.

Confidence:
3

ARNI (sacubitril/valsartan) is the preferred first-line agent over ACE inhibitors or ARBs to reduce cardiovascular mortality and hospitalization in symptomatic HFrEF patients.

Confidence:
4

SGLT2 inhibitors (dapagliflozin or empagliflozin) are indicated for all HFrEF patients regardless of the presence of type 2 diabetes mellitus.

Confidence:
5

Loop diuretics (e.g., furosemide) are used exclusively for symptom management of volume overload and do not provide a mortality benefit.

Confidence:
6

An implantable cardioverter-defibrillator (ICD) is indicated for patients with an ejection fraction ≤ 35% despite at least 3 months of optimal GDMT to prevent sudden cardiac death.

Confidence:
7

Cardiac resynchronization therapy (CRT) is indicated for patients with HFrEF who have a left bundle branch block (LBBB) with a QRS duration ≥ 150 ms.

Confidence:

Vignette unlocked

A 68-year-old male presents with progressive dyspnea on exertion, orthopnea, and bilateral lower extremity edema. Physical examination reveals jugular venous distension, a displaced apical impulse, and an S3 gallop. His past medical history is significant for a myocardial infarction five years ago. An echocardiogram demonstrates a dilated left ventricle with an ejection fraction of 30%.

Which of the following medication classes provides the greatest mortality benefit and should be initiated as part of the foundational therapy for this patient?

+Reveal answer

ARNI (sacubitril/valsartan)

The patient has HFrEF, and current guidelines prioritize ARNI as the preferred first-line agent over ACE inhibitors or ARBs to reduce mortality and hospitalizations.

Mo

Depth

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High yield triage

Etiology / Epidemiology

Ischemic heart disease and chronic hypertension are the leading causes. Patients present with progressive dyspnea and volume overload.

Clinical Manifestations

Classic findings include orthopnea, paroxysmal nocturnal dyspnea, and an S3 gallop. JVD and pulmonary rales are pathognomonic.

Diagnosis

Transthoracic echocardiogram is the gold standard. LVEF ≤ 40% confirms the diagnosis of HFrEF.

Treatment

Initiate ARNI (or ACEi/ARB), beta-blocker, MRA, and SGLT2 inhibitor. Avoid NSAIDs due to fluid retention.

Prognosis

High mortality risk; 50% mortality at 5 years. Monitor potassium and creatinine closely.

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Epidemiology & Etiology

HFrEF is most commonly caused by coronary artery disease and myocardial infarction. Other major etiologies include dilated cardiomyopathy, chronic uncontrolled hypertension, and valvular disease. It is a syndrome of progressive ventricular remodeling and pump failure.

Pertinent Anatomy

The left ventricle undergoes eccentric hypertrophy and dilation, leading to increased wall stress. This structural change impairs systolic contraction and reduces stroke volume.

Pathophysiology

Reduced cardiac output triggers the neurohormonal axis, activating the RAAS and sympathetic nervous system. Chronic activation leads to maladaptive remodeling, fibrosis, and worsening myocardial contractility. This cycle creates a state of persistent fluid retention and increased afterload.

Clinical Manifestations

Patients typically report exertional dyspnea, orthopnea, and PND. Physical exam reveals displaced apical impulse, S3 gallop, and peripheral edema. Acute decompensation is marked by Cheyne-Stokes respiration and severe respiratory distress.

Diagnosis

The transthoracic echocardiogram is the diagnostic gold standard to assess wall motion and LVEF ≤ 40%. BNP > 100 pg/mL or NT-proBNP > 300 pg/mL supports the diagnosis in the acute setting. A CXR may show Kerley B lines and cardiomegaly.

Treatment

The 'four pillars' of therapy include ARNI (preferred over ACEi/ARB), beta-blockers (bisoprolol, carvedilol, or metoprolol succinate), MRA (spironolactone), and SGLT2 inhibitors (dapagliflozin/empagliflozin). Contraindications for ARNI include a history of angioedema. Use loop diuretics for symptomatic volume management.

Prognosis

Prognosis is poor, with 50% mortality at 5 years post-diagnosis. Patients are at high risk for sudden cardiac death due to ventricular arrhythmias, often requiring an ICD if LVEF remains low despite optimal medical therapy.

Differential Diagnosis

HFpEF: LVEF ≥ 50% with diastolic dysfunction

COPD: absence of S3 gallop and elevated BNP

Cirrhosis: peripheral edema without pulmonary congestion

Nephrotic syndrome: generalized edema with proteinuria

Pulmonary embolism: acute dyspnea with clear lungs on auscultation