7.2 Heart Failure, Cardiomyopathies & Valvular Disease
Key Takeaways
- Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF, LVEF <=40%) requires four foundational drug classes that reduce mortality: ARNI (sacubitril/valsartan), evidence-based beta-blockers (carvedilol, metoprolol succinate, bisoprolol), mineralocorticoid receptor antagonists (spironolactone or eplerenone), and SGLT2 inhibitors (dapagliflozin or empagliflozin).
- When transitioning a patient from an ACE inhibitor to sacubitril/valsartan (ARNI), a mandatory 36-hour washout period must be observed to prevent severe angioedema caused by dual inhibition of neprilysin and ACE.
- Hypertrophic cardiomyopathy (HCM) features asymmetric septal hypertrophy causing dynamic left ventricular outflow tract (LVOT) obstruction; the characteristic systolic ejection murmur increases with maneuvers that decrease LV preload or afterload (Valsalva, standing) and decreases with maneuvers that increase LV volume or afterload (squatting, handgrip, passive leg raise).
- Primary implantable cardioverter-defibrillator (ICD) placement is indicated for primary prevention of sudden cardiac death in patients with HFrEF (LVEF <=35%) who remain symptomatic (NYHA Class II-III) despite at least 3 months of optimal GDMT.
- Aortic stenosis intervention (surgical aortic valve replacement [SAVR] or transcatheter aortic valve replacement [TAVR]) is indicated for any patient with symptomatic severe aortic stenosis (valve area <1.0 cm2, mean gradient >40 mmHg, or peak velocity >4.0 m/s), or asymptomatic patients with LVEF <50%.
Heart Failure, Cardiomyopathies & Valvular Disease
Heart failure (HF) and valvular heart diseases require a comprehensive understanding of myocardial mechanics, neurohormonal pathways, physical examination findings, and guideline-directed interventions. On USMLE Step 2 CK, questions emphasize pharmacologic mortality benefits, hemodynamic profiling of acute decompensation, cardiomyopathy differentiation, and indications for valve repair or replacement.
Heart Failure Classification & Clinical Diagnosis
Heart failure is defined by the inability of the heart to pump sufficient blood to meet metabolic demands or doing so only at elevated filling pressures.
Phenotypic Classification
- Heart Failure with Reduced Ejection Fraction (HFrEF): Left ventricular ejection fraction (LVEF) $\le 40%$. Primary defect is impaired systolic contraction (inotropic failure).
- Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF): LVEF $41\text{--}49%$.
- Heart Failure with Preserved Ejection Fraction (HFpEF): LVEF $\ge 50%$. Primary defect is impaired diastolic relaxation and compliance (lusitropic failure), frequently secondary to chronic hypertension, aging, obesity, or amyloidosis.
Diagnostic Biomarkers & Physical Exam
- B-type Natriuretic Peptide (BNP $>100\text{ pg/mL}$) & NT-proBNP ($>300\text{ pg/mL}$): Released by ventricular myocytes in response to wall stretch. Excellent negative predictive value to rule out heart failure in acute dyspnea.
- Physical Exam Findings: S3 gallop (pathognomonic for LV volume overload in HFrEF), elevated jugular venous pressure (JVP $>8\text{ cm H}_2\text{O}$), hepatojugular reflux, bilateral basilar crackles, and peripheral pitting edema. An S4 gallop indicates atrial contraction into a stiffened LV (characteristic of HFpEF and LVH).
Guideline-Directed Medical Therapy (GDMT) for HFrEF
Modern management of HFrEF (LVEF $\le 40%$) centers on four foundational pillars of GDMT that independently reduce overall mortality, heart failure hospitalizations, and sudden cardiac death:
| GDMT Pillar Drug Class | Specific Agents & Dosages | Clinical Pearls & Mandatory Precautions |
|---|---|---|
| 1. Angiotensin Receptor-Neprilysin Inhibitor (ARNI) | Sacubitril / Valsartan | Preferred over ACEi/ARB. Mandatory 36-hour washout period required when switching from an ACE inhibitor to prevent severe angioedema. |
| 2. Evidence-Based Beta-Blockers | Carvedilol, Metoprolol Succinate, Bisoprolol | Reduces mortality by decreasing sympathetic drive. Do not initiate during acute decompensation; introduce only when euvolemic. |
| 3. Mineralocorticoid Receptor Antagonists (MRA) | Spironolactone, Eplerenone | Reduces aldosterone-mediated myocardial fibrosis. Monitor serum potassium ($\text{K}^+ <5.0\text{ mEq/L}$) and renal function ($\text{CrCl} >30\text{ mL/min}$). |
| 4. SGLT2 Inhibitors | Dapagliflozin, Empagliflozin | Reduces heart failure hospitalizations and cardiovascular death regardless of whether the patient has type 2 diabetes. |
Additional Pharmacologic & Device Therapies
- Hydralazine plus Isosorbide Dinitrate: Mortality benefit in self-identified Black patients with NYHA Class III–IV HFrEF despite optimal GDMT, or patients intolerant to ARNI/ACEi/ARB due to renal failure or hyperkalemia.
- Loop Diuretics (Furosemide, Bumetanide): Essential for symptom relief of volume overload. Does NOT confer a mortality benefit.
- Ivabradine: Selective $I_f$ current inhibitor in the SA node. Indicated in patients with symptomatic HFrEF (LVEF $\le 35%$), in sinus rhythm with a resting heart rate $\ge 70\text{ bpm}$ despite maximum tolerated beta-blocker therapy.
- Implantable Cardioverter-Defibrillator (ICD): Primary prevention of sudden cardiac death in HFrEF with LVEF $\le 35%$ and NYHA Class II–III symptoms after $\ge 3\text{ months}$ of optimal GDMT, or post-MI LVEF $\le 35%$ after $\ge 40\text{ days}$.
- Cardiac Resynchronization Therapy (CRT): Biventricular pacing indicated for LVEF $\le 35%$, sinus rhythm, LBBB morphology, and QRS duration $\ge 150\text{ ms}$.
Cardiomyopathies: Clinical Spectrum & Differentiation
| Feature | Dilated Cardiomyopathy (DCM) | Hypertrophic Cardiomyopathy (HCM) | Restrictive Cardiomyopathy (RCM) |
|---|---|---|---|
| Pathophysiology | Ventricular dilation, systolic dysfunction (LVEF $<40%$). | Asymmetric septal hypertrophy, dynamic LVOT obstruction, diastolic dysfunction. | Rigid myocardium, severe diastolic dysfunction, preserved LVEF ($>50%$). |
| Etiologies | Idiopathic, viral myocarditis (Coxsackie B), alcohol abuse, doxorubicin, peripartum, ischemia. | Autosomal dominant mutations in sarcomeric proteins (MYH7, MYBPC3). | Cardiac amyloidosis, sarcoidosis, hemochromatosis, radiation, scleroderma. |
| Physical Exam & EKG | S3 gallop, cardiomegaly, displaced PMI. | Harsh systolic ejection murmur at LLSB. S4 gallop. | Kussmaul sign (JVP rises on inspiration). EKG: Low voltage despite thick LV walls (amyloid). |
| Treatment Notes | Standard GDMT for HFrEF. Abstinence from alcohol. | Beta-blockers or verapamil (first-line). Avoid diuretics, nitrates, and inotropes. | Treat underlying etiology. Diuretics for volume overload. Heart transplant. |
Diagnostic Maneuvers in Hypertrophic Cardiomyopathy
In HCM with dynamic LVOT obstruction, systolic anterior motion (SAM) of the anterior mitral valve leaflet contacts the hypertrophied septum during systole.
- Maneuvers that DECREASE LV Preload/Volume (Valsalva strain phase, sudden standing, nitroglycerin): INCREASE murmur intensity (smaller LV chamber size worsens obstruction).
- Maneuvers that INCREASE LV Preload/Afterload (Squatting, passive leg raise, sustained handgrip): DECREASE murmur intensity (larger LV chamber separates septum from mitral valve).
Valvular Heart Diseases & Surgical Indications
Valvular Lesion Diagnostic Summary
| Valvular Lesion | Physical Exam & Murmur Characteristics | Classic Clinical Scenario & Complications |
|---|---|---|
| Aortic Stenosis (AS) | Crescendo-decrescendo systolic murmur at 2nd RICS radiating to carotids. Pulsus parvus et tardus (weak, delayed carotid pulse). Soft/absent S2. | SAD triad: Syncope, Angina, Dyspnea. Caused by age-related calcification or bicuspid aortic valve. |
| Aortic Regurgitation (AR) | Early diastolic decrescendo murmur at 3rd LICS. Bounding pulses (Water-hammer pulse), wide pulse pressure, Austin Flint murmur. | Endocarditis, aortic dissection, Marfan syndrome. LV volume overload leading to eccentric hypertrophy. |
| Mitral Stenosis (MS) | Opening snap followed by mid-diastolic rumbling murmur with presystolic accentuation at apex (left lateral decubitus position). | History of Rheumatic Fever (Group A Strep). Causes atrial fibrillation, LA enlargement, and Ortner syndrome (hoarseness from recurrent laryngeal nerve compression). |
| Mitral Regurgitation (MR) | Holosystolic murmur at apex radiating to axilla. Prominent S3 gallop. | Ischemic papillary muscle rupture, MVP, endocarditis. Acute MR causes sudden pulmonary edema. |
| Mitral Valve Prolapse (MVP) | Mid-systolic click followed by late systolic murmur at apex. | Young females, connective tissue disorders. Squatting delays click/murmur; standing moves click earlier. |
Surgical Criteria for Valvular Interventions
- Severe Aortic Stenosis Criteria: Valve area $<1.0\text{ cm}^2$, mean pressure gradient $>40\text{ mmHg}$, or peak velocity $>4.0\text{ m/s}$.
- Indications for AVR (SAVR or TAVR): Presence of any symptoms (syncope, angina, dyspnea), OR asymptomatic with LVEF $<50%$, OR undergoing concurrent cardiac surgery.
- Mitral Regurgitation: Surgical repair or replacement indicated for symptomatic severe MR, or asymptomatic severe MR with LVEF 30–60% or LV end-systolic diameter (LVESD) $\ge 40\text{ mm}$.
- Mitral Stenosis: Percutaneous mitral balloon commissurotomy (PMBC) indicated for symptomatic moderate-to-severe MS with favorable valve morphology and absence of LA thrombus.
A 22-year-old college athlete undergoes routine pre-participation screening. He reports no shortness of breath, chest pain, or palpitations, but notes that his father died suddenly at age 34 while playing basketball. Physical examination reveals a 3/6 harsh systolic ejection murmur heard best at the left lower sternal border. The murmur increases significantly in intensity when the patient performs a Valsalva maneuver and decreases when he transitions from standing to a deep squat. Echocardiogram confirms asymmetric septal hypertrophy with dynamic left ventricular outflow tract obstruction. Which of the following is the most appropriate initial pharmacologic therapy?
A 58-year-old man with long-standing ischemic heart failure and an ejection fraction of 28% presents to the cardiology clinic for routine follow-up. He is currently taking enalapril 10 mg twice daily, carvedilol 25 mg twice daily, and spironolactone 25 mg daily. His blood pressure is 126/78 mmHg and pulse is 64/min. The cardiologist decides to transition the patient from enalapril to sacubitril/valsartan to further reduce cardiovascular mortality. What critical instruction must be given to the patient regarding this transition?
An 81-year-old man presents to the clinic complaining of exertional dyspnea and two recent episodes of presyncope while walking uphill. On physical examination, his carotid pulse is weak and delayed (pulsus parvus et tardus). Auscultation reveals a harsh crescendo-decrescendo systolic murmur at the second right intercostal space that radiates to the carotid arteries bilaterally, along with a soft, single second heart sound. Echocardiography demonstrates a aortic valve area of 0.7 cm² and a mean aortic valve pressure gradient of 48 mmHg. What is the most appropriate definitive management for this patient?