5.2 Heart Failure & Cardiomyopathies
Key Takeaways
- Foundational guideline-directed medical therapy (GDMT) for HFrEF consists of an ARNI (sacubitril/valsartan), a beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), an MRA (spironolactone or eplerenone), and an SGLT2 inhibitor.
- Acute decompensated heart failure is managed based on perfusion and congestion profiles; volume overload (wet) requires IV loop diuretics, while cardiogenic shock (cold and wet) necessitates IV inotropes like dobutamine.
- Hypertrophic cardiomyopathy features asymmetric septal hypertrophy and LVOT obstruction; first-line therapy is beta-blockers or verapamil, while vasodilators, high-dose diuretics, and inotropes are contraindicated.
Heart Failure & Cardiomyopathies
Step 3 Clinical Focus: The management of heart failure (HF) requires understanding the distinction between systolic and diastolic dysfunction, the classification and management of acute decompensated heart failure (ADHF), and the systematic implementation of guideline-directed medical therapy (GDMT). Additionally, differentiating hypertrophic, dilated, and restrictive cardiomyopathies is a major exam focus.
Systolic vs. Diastolic Dysfunction
Heart failure is clinically categorized by left ventricular ejection fraction (LVEF). Heart Failure with reduced Ejection Fraction (HFrEF, LVEF ≤ 40%) is primarily characterized by impaired myocardial contractility (systolic dysfunction), leading to eccentric hypertrophy and ventricular dilatation. Common causes include ischemic heart disease, dilated cardiomyopathy, and chronic hypertension. Heart Failure with preserved Ejection Fraction (HFpEF, LVEF ≥ 50%) is characterized by impaired myocardial relaxation and increased ventricular stiffness during diastole (diastolic dysfunction), leading to elevated filling pressures despite normal cavity size. Common etiologies include aging, long-standing hypertension, obesity, and amyloidosis. Both conditions present with dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. Initial diagnostic workup includes a B-type natriuretic peptide (BNP) level to rule out non-cardiac causes of dyspnea, followed by a transthoracic echocardiogram to assess ejection fraction, chamber sizes, and valvular function.
Acute Decompensated Heart Failure (ADHF)
ADHF represents a sudden worsening of heart failure symptoms, requiring prompt assessment and classification based on hemodynamic profiles: perfusion (warm vs. cold) and congestion (dry vs. wet). Most patients present as "warm and wet" (adequate perfusion, signs of volume overload). Initial management focuses on aggressive intravenous loop diuretics (e.g., furosemide) using double the patient's home oral daily dose. If the patient is hypertensive, IV vasodilators (such as nitroglycerin or nitroprusside) are added to reduce preload and afterload. For patients who are "cold and wet" (impaired perfusion and fluid overload, signaling cardiogenic shock), intravenous inotropic support with agents like dobutamine (a beta-1 agonist) or milrinone (a phosphodiesterase-3 inhibitor) is indicated to improve cardiac output. In these patients, vasodilators must be avoided if hypotension is present. Non-invasive positive pressure ventilation should be initiated for acute pulmonary edema with respiratory distress to reduce preload. Serum electrolytes, renal function, and cardiac enzymes must be monitored closely during aggressive diuresis, as rapid fluid removal can precipitate acute kidney injury.
Guideline-Directed Medical Therapy (GDMT) for HFrEF
The modern therapeutic framework for HFrEF is built upon four foundational pharmacological pillars, initiated and uptitrated to target doses as tolerated:
- Angiotensin Receptor-Neprilysin Inhibitor (ARNI): Sacubitril/valsartan is preferred over ACE inhibitors or ARBs as first-line therapy to reduce hospitalization and mortality. If switching from an ACE inhibitor to an ARNI, a 36-hour washout period is mandatory to prevent life-threatening angioedema.
- Beta-blockers: Specifically carvedilol, metoprolol succinate, or bisoprolol. These must be initiated only when the patient is stable and euvolemic, as starting them during acute decompensation can worsen heart failure.
- Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone, indicated for patients with NYHA class II-IV symptoms and LVEF ≤ 35%, provided renal function is adequate (creatinine < 2.5 mg/dL in men) and potassium is monitored (< 5.0 mEq/L).
- Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Empagliflozin or dapagliflozin, which reduce cardiovascular mortality and heart failure hospitalizations regardless of diabetes status.
Secondary therapies include loop diuretics for volume control, hydralazine/isosorbide dinitrate for Black patients with persistent NYHA class III-IV symptoms despite optimal GDMT, and ivabradine for patients in sinus rhythm with a resting heart rate ≥ 70 beats per minute on maximally tolerated beta-blockers. Device therapies, including implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death and cardiac resynchronization therapy (CRT) for patients with LVEF ≤ 35%, sinus rhythm, and LBBB with QRS duration ≥ 150 ms, are evaluated after at least 3 months of optimal GDMT.
Cardiomyopathies
- Hypertrophic Cardiomyopathy (HCM): An autosomal dominant condition caused by mutations in sarcomeric proteins (e.g., beta-myosin heavy chain). It features asymmetric septal hypertrophy, leading to left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion (SAM) of the mitral valve. Physical exam reveals a harsh systolic crescendo-decrescendo murmur at the left sternal border that increases with maneuvers that decrease preload (Valsalva, standing) and decreases with maneuvers that increase preload or afterload (squatting, handgrip). This dynamic change distinguishes it from aortic stenosis, which increases with squatting and decreases with Valsalva. First-line medical therapy consists of beta-blockers or non-dihydropyridine calcium channel blockers (verapamil) to prolong diastole and increase LV filling. Avoid vasodilators, high-dose diuretics, and inotropes, which worsen obstruction. Surgical myectomy or mavacamten are indicated for refractory symptoms.
- Dilated Cardiomyopathy (DCM): Characterized by left ventricular enlargement and systolic dysfunction. Etiologies include genetic mutations (e.g., titin gene), viral myocarditis (coxsackievirus B), toxic exposures (alcohol, cocaine, doxorubicin), peripartum state, and Chagas disease. Differentiating doxorubicin cardiotoxicity (myocyte necrosis, irreversible) from trastuzumab-induced cardiotoxicity (myocardial dysfunction, reversible) is highly relevant for oncology patients. Treatment follows standard HFrEF GDMT, alongside abstinence from toxins and management of the underlying cause.
- Restrictive Cardiomyopathy (RCM): Characterized by normal or decreased diastolic volume of one or both ventricles with normal wall thickness, but severely impaired ventricular filling. Causes include systemic amyloidosis (either light chain AL or transthyretin ATTR), sarcoidosis, hemochromatosis, and radiation therapy. Diagnosis is supported by low voltage on ECG despite thickened ventricular walls on echocardiogram (classically a speckled appearance), cardiac MRI, or endomyocardial biopsy. Treatment involves careful volume management with diuretics, alongside disease-specific therapies (e.g., tafamidis for ATTR amyloidosis).
A 64-year-old man with a history of chronic heart failure with reduced ejection fraction (LVEF 30%) is evaluated during a routine clinic visit. He reports mild dyspnea when climbing one flight of stairs (NYHA Class II). He is currently taking lisinopril 10 mg daily, metoprolol succinate 100 mg daily, and empagliflozin 10 mg daily. His blood pressure is 118/72 mmHg, heart rate is 64 beats per minute, and potassium is 4.1 mEq/L. He is euvolemic on physical exam. What is the most appropriate next step to optimize his guideline-directed medical therapy?
A 24-year-old male athlete presents for a sports physical. He reports occasional lightheadedness during intense exertion but is otherwise asymptomatic. His family history is notable for the sudden cardiac death of his uncle at age 29. On physical examination, a harsh systolic crescendo-decrescendo murmur is heard at the left lower sternal border. The murmur increases in intensity when the patient stands up from a squatting position. What is the most appropriate initial pharmacological therapy for this patient's condition?
A 52-year-old woman is admitted to the hospital with a 3-day history of progressive dyspnea, orthopnea, and lower extremity edema. Her blood pressure is 85/50 mmHg, heart rate is 110 beats per minute, and oxygen saturation is 88% on room air. Physical examination reveals cool extremities, weak peripheral pulses, jugular venous distention, and bilateral pulmonary crackles. Echocardiogram shows an ejection fraction of 20% with global hypokinesis. What is the most appropriate immediate management?