Heart failure with reduced ejection fraction (HFrEF)

A 68 year old male with a history of hypertension, type 2 diabetes mellitus, and coronary artery disease presents with progressive shortness of breath over the past 2 weeks. He reports fatigue, orthopnea, paroxysmal nocturnal dyspnea, and bilateral lower extremity swelling, along with recent weight gain. On examination, he appears dyspneic with elevated jugular venous pressure, bilateral pitting edema, and diffuse crackles on lung auscultation. Cardiac examination reveals a displaced apical impulse and an S3 gallop. Chest X-ray shows cardiomegaly, pulmonary congestion, and bilateral pleural effusions. Laboratory evaluation reveals elevated BNP and NT-proBNP, worsening renal function, and hyponatremia. Echocardiography demonstrates a dilated left ventricle, global hypokinesis, and LVEF 35 percent. Diagnosis?

Diagnosis is acute decompensated heart failure with reduced ejection fraction (HFrEF), likely secondary to ischemic cardiomyopathy.

1. Definition

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome characterized by:

1. Symptoms and/or signs of heart failure
2. Left ventricular ejection fraction ≤40 percent
3. Often supported by elevated natriuretic peptides or objective evidence of structural heart disease

It results from impaired myocardial contractility, leading to reduced cardiac output, elevated filling pressures, and neurohormonal activation.

2. Etiology

2.1 Ischemic

1. Coronary artery disease
2. Prior myocardial infarction

2.2 Non-ischemic

1. Dilated cardiomyopathy
2. Myocarditis
3. Alcohol or cocaine toxicity
4. Chemotherapy-induced cardiomyopathy
5. Peripartum cardiomyopathy

2.3 Pressure or Volume Overload

1. Chronic hypertension
2. Aortic stenosis
3. Mitral or aortic regurgitation

2.4 Tachycardia-induced

1. Atrial fibrillation
2. Supraventricular tachycardia

2.5 Infiltrative and Metabolic

1. Amyloidosis
2. Hemochromatosis
3. Sarcoidosis

3. Pathophysiology

3.1 Core Mechanism

1. Reduced contractility → decreased stroke volume
2. Decreased cardiac output → hypoperfusion

3.2 Neurohormonal Activation

1. RAAS activation → vasoconstriction and sodium retention
2. Sympathetic activation → increased heart rate and oxygen demand
3. ADH release → water retention and hyponatremia

3.3 Ventricular Remodeling

1. Left ventricular dilation with eccentric hypertrophy
2. Increased wall stress
3. Fibrosis and myocyte loss

3.4 Hemodynamic Consequences

1. Increased LV end-diastolic pressure → pulmonary congestion
2. Increased right-sided pressures → systemic congestion
3. Reduced renal perfusion → worsening renal function

3.5 Vicious Cycle

Low cardiac output → neurohormonal activation → remodeling → further decline in ejection fraction

4. Hemodynamic Profile

1. Decreased cardiac output and cardiac index
2. Increased LV end-diastolic pressure
3. Increased pulmonary capillary wedge pressure (>18 mm Hg)
4. Increased systemic vascular resistance
5. Increased right atrial pressure

5. Classification

5.1 By Ejection Fraction

1. HFrEF ≤40 percent
2. HFmrEF 41–49 percent
3. HFpEF ≥50 percent

5.2 NYHA Functional Classification

1. Class I: No limitation
2. Class II: Mild limitation
3. Class III: Marked limitation
4. Class IV: Symptoms at rest

5.3 ACC/AHA Staging

1. Stage A: At risk
2. Stage B: Structural disease without symptoms
3. Stage C: Symptomatic heart failure
4. Stage D: Refractory heart failure

6. Clinical Features

6.1 Symptoms

1. Dyspnea
2. Orthopnea
3. Paroxysmal nocturnal dyspnea
4. Fatigue
5. Peripheral edema
6. Weight gain
7. Early satiety

6.2 Signs

1. Elevated jugular venous pressure
2. S3 gallop
3. Pulmonary crackles
4. Displaced apical impulse
5. Peripheral edema

6.3 Advanced Features

1. Hypotension
2. Cold extremities
3. Cardiorenal syndrome

7. Diagnosis

7.1 Laboratory

1. Elevated BNP or NT-proBNP
2. Age-adjusted NT-proBNP thresholds may support diagnosis

1.  >450 pg/mL if <50 years

2. >900 pg/mL if 50–75 years

3. >1800 pg/mL if >75 years

3. Hyponatremia indicates severe disease
4. Elevated creatinine indicates renal involvement

7.2 Imaging

1. Chest X-ray shows cardiomegaly, pulmonary edema, and pleural effusions

7.3 ECG

1. Left ventricular hypertrophy
2. Q waves
3. Left bundle branch block
4. Arrhythmias

7.4 Echocardiography

1. LVEF ≤40 percent
2. Dilated left ventricle
3. Hypokinesis
4. Valvular abnormalities

7.5 Advanced Evaluation

1. Cardiac MRI for infiltrative or inflammatory disease
2. Coronary angiography for ischemic evaluation
3. Right heart catheterization for hemodynamic assessment

8. Management

8.1 Guideline-Directed Medical Therapy

1. ARNI preferred or ACE inhibitor or ARB
2. Evidence-based beta blockers (metoprolol succinate, carvedilol, bisoprolol)
3. Mineralocorticoid receptor antagonists
4. SGLT2 inhibitors

8.2 Symptom Relief

1. Loop diuretics for volume overload
2. Add thiazide diuretics if resistant

8.3 Additional Therapies

1. Hydralazine plus isosorbide dinitrate in selected patients
2. Ivabradine if heart rate ≥70 in sinus rhythm
3. Digoxin reduces hospitalization
4. Intravenous iron in iron deficiency
5. Anticoagulation in atrial fibrillation

8.4 Device Therapy

1. ICD indicated if:
• LVEF ≤35 percent
• On optimal medical therapy for ≥3 months
• Life expectancy >1 year
2. CRT indicated if:
• LVEF ≤35 percent
• Sinus rhythm
• LBBB with QRS ≥150 ms
• Persistent symptoms despite GDMT

9. Acute Decompensated Heart Failure

1. Oxygen or noninvasive ventilation if hypoxic
2. Intravenous loop diuretics are first line
3. Vasodilators such as nitroglycerin in hypertensive patients
4. Inotropes for hypoperfusion or cardiogenic shock

10. Prognosis and Monitoring

1. Prognosis is variable and depends on disease severity
2. Poor prognostic factors:
• Low ejection fraction
• Elevated BNP
• Renal dysfunction
• Hyponatremia
3. Monitor renal function and electrolytes regularly
4. Repeat echocardiography after clinical change or therapy optimization

11. Key Clinical Insight

Dyspnea + orthopnea + S3 gallop + LVEF ≤40 percent = HFrEF

Congestion versus hypoperfusion guides management

12. Exam Level Pearls

1. Four pillar therapy reduces mortality and hospitalizations
2. S3 gallop indicates systolic dysfunction
3. BNP supports diagnosis
4. Do not discontinue GDMT even if ejection fraction improves
5. LVEF ≤35 percent indicates need for ICD evaluation
6. LBBB with wide QRS indicates benefit from CRT
7. IV loop diuretics are first line in acute decompensation