Cardiomyopathies

Non-modifiable / genetic

• Sarcomeric gene mutations: autosomal dominant MYH7 and MYBPC3 mutations underlie most HCM; titin and lamin A/C mutations dominate familial DCM. Family history of cardiomyopathy or unexplained sudden death before age 50 is the single most important stem clue.
• X-linked and syndromic disease: Duchenne/Becker dystrophinopathy and Fabry disease (α-galactosidase A deficiency); Friedreich ataxia causes concentric hypertrophy.
• Hereditary infiltration: HFE hemochromatosis (autosomal recessive) and hereditary transthyretin amyloidosis — the Val122Ile variant is enriched in Black patients and presents as late-onset restrictive disease.
• Age, male sex, and Black race increase risk of amyloid and hypertensive-phenotype cardiomyopathy.

Modifiable / acquired — toxic

• Ethanol: chronic heavy use causes dose-dependent myocyte injury and dilated remodeling; abstinence can reverse it.
• Anthracyclines (doxorubicin): cumulative-dose, largely irreversible topoisomerase-IIβ/oxidative injury. Trastuzumab causes typically reversible HER2-mediated dysfunction; risk is potentiated by prior anthracycline and by chest radiation.
• Cocaine, methamphetamine, chloroquine, and thiamine deficiency (wet beriberi).

Modifiable / acquired — inflammatory and infectious

• Viral myocarditis: coxsackie B and other enteroviruses, parvovirus B19, adenovirus, HIV; immune checkpoint inhibitors cause fulminant myocarditis.
• Chagas disease (Trypanosoma cruzi): Latin American origin, apical aneurysm plus RBBB.
• Cardiac sarcoidosis — granulomatous infiltration with high-grade AV block in a young patient.
• Eosinophilic (Löffler) endomyocarditis: hypereosinophilia → endocardial fibrosis and apical thrombus.

Modifiable / physiologic and iatrogenic

• Peripartum state: risk rises with multiparity, age >30, twin gestation, preeclampsia, and Black race.
• Uncontrolled hypertension, obesity, diabetes, obstructive sleep apnea, tachyarrhythmia (tachycardia-mediated cardiomyopathy), and mediastinal radiation.
• Catecholamine surge: takotsubo after emotional or physical stress, and pheochromocytoma.
• Sustained ischemia is excluded by definition from primary cardiomyopathy, but coronary disease is the leading mimic and must be ruled out.

DILATED CARDIOMYOPATHY (DCM)

• Sarcomeric dysfunction: Mutations in genes encoding contractile proteins (titin, β-myosin heavy chain, troponin) lead to impaired force generation and increased myocyte apoptosis
• Excitation-contraction coupling abnormalities: Disrupted calcium handling via RyR2 (ryanodine receptor) and SERCA2 dysfunction causes reduced contractility
• Progressive ventricular remodeling: Eccentric hypertrophy (chamber dilation with wall thinning) from chronic volume overload, activation of RAAS and sympathetic nervous system, inflammatory cytokines (TNF-α, IL-6), and extracellular matrix degradation by matrix metalloproteinases
• Mitochondrial dysfunction: Impaired ATP production and increased oxidative stress in genetic and acquired forms
• Common etiologies: Genetic (40% familial, autosomal dominant most common), viral myocarditis, alcohol (chronic ethanol toxicity), peripartum, drugs (anthracyclines, trastuzumab), infiltrative diseases

HYPERTROPHIC CARDIOMYOPATHY (HCM)

• Sarcomeric protein mutations: 50-60% of cases caused by heterozygous mutations in β-myosin heavy chain, myosin-binding protein C (MYBPC3), or troponins
• Left ventricular hypertrophy (LVH): Excessive myocyte growth and disarray; characteristic asymmetric septum predominance but can be concentric or apical
• Diastolic dysfunction: Impaired relaxation and increased stiffness from fibrosis and abnormal calcium dynamics
• Dynamic left ventricular outflow tract (LVOT) obstruction: In ~70% of HCM patients, anterior motion of anterior mitral leaflet (SAM) narrows LVOT during systole, increasing gradient with decreased preload (Valsalva, standing) and decreased afterload
• Myocardial fibrosis: Diffuse and replacement fibrosis creates arrhythmogenic substrate and contributes to sudden death risk

RESTRICTIVE CARDIOMYOPATHY (RCM)

• Increased ventricular stiffness: Fibrosis, amyloid infiltration, or iron deposition impairs diastolic filling
• Preserved or near-normal systolic function: Classic hemodynamic pattern with "square root sign" (rapid early filling followed by plateau in diastolic pressure)
• Atrial dilation: Secondary to elevated filling pressures without ventricular dilation
• Primary RCM: Genetic (sarcomeric mutations, desmin, troponins) or idiopathic
• Secondary RCM: Cardiac amyloidosis (AL or transthyretin), hemochromatosis, sarcoidosis, radiation, Fabry disease

DILATED CARDIOMYOPATHY

• Dyspnea and orthopnea: From pulmonary edema secondary to elevated left ventricular end-diastolic pressure (LVEDP) and systolic dysfunction
• Fatigue and exercise intolerance: Due to inadequate cardiac output and poor peripheral perfusion
• Peripheral edema, ascites, hepatomegaly: Signs of right heart failure and elevated systemic venous pressure
• Palpitations: Often from premature ventricular contractions (PVCs) or atrial fibrillation (common in DCM due to chamber dilation)
• Syncope or presyncope: From arrhythmias or severely reduced cardiac output
• Sudden cardiac death: Can be the first manifestation in younger patients; risk often unpredictable

HYPERTROPHIC CARDIOMYOPATHY

• Dyspnea: From diastolic dysfunction and elevated filling pressures; may worsen with exertion (LVOT obstruction increases with exercise)
• Chest pain: Anginal symptoms from increased myocardial demand, microvascular dysfunction, or compression of coronary arteries (paradoxical in absence of CAD)
• Syncope or near-syncope: Particularly with exertion; caused by dynamic LVOT obstruction, arrhythmias, or inadequate BP response to exercise
• Palpitations: From atrial fibrillation (10-25% of patients) or ventricular arrhythmias
• Sudden cardiac death: Most common cause of SCD in young athletes; often first presentation
• Murmur: Harsh systolic ejection murmur best heard at left lower sternal border; increases with Valsalva/standing (reduced preload increases gradient); decreases with squatting/handgrip (increased afterload)
• Often asymptomatic: Found incidentally on screening or family evaluation

RESTRICTIVE CARDIOMYOPATHY

• Dyspnea and exercise intolerance: From impaired diastolic filling and elevated filling pressures
• Peripheral edema and ascites: Signs of right heart failure; may predominate
• Syncope: From reduced cardiac output, especially if accompanied by conduction abnormalities
• Palpitations: From atrial fibrillation (very common in RCM)
• Presentation mimics constrictive pericarditis: Often difficult to distinguish clinically

IMPORTANT CLINICAL PEARLS

• Young patient with sudden cardiac death → think HCM until proven otherwise
• Alcohol-induced dilated cardiomyopathy typically presents in middle-aged men with years of heavy use
• Peripartum cardiomyopathy: fulminant heart failure in third trimester or first 5 months postpartum; 25-50% recover, 50% require transplant
• Stress cardiomyopathy (Takotsubo): mimics acute MI with apical ballooning on echo; associated with emotional/physical stress; usually recovers

ELECTROCARDIOGRAM (ECG)

• Dilated cardiomyopathy: Non-specific findings including sinus tachycardia, ST changes, T-wave abnormalities, conduction delays (bundle branch block common), low voltage (in restrictive/infiltrative disease), Q waves (mimicking prior MI)
• Hypertrophic cardiomyopathy: Deep Q waves in lateral and inferior leads (due to LVH and septal depolarization), T-wave inversion (especially in lateral leads), LVH with repolarization abnormalities, left atrial enlargement, short PR interval (in some genetic HCM)
• Restrictive cardiomyopathy: Low voltage, atrial fibrillation, conduction abnormalities; depends on underlying cause

• Dilated cardiomyopathy: Increased LV end-diastolic dimension (>55 mm), decreased ejection fraction (<40%, typically 15-35%), chamber dilation (eccentric remodeling), global hypokinesis, secondary mitral regurgitation common
• Hypertrophic cardiomyopathy: LV wall thickness ≥15 mm (13 mm in presence of family history), asymmetric septal hypertrophy, small LV cavity, mitral valve SAM, LVOT obstruction with gradient (dynamic), diastolic dysfunction, left atrial enlargement
• Restrictive cardiomyopathy: Biatrial enlargement (disproportionate to ventricular size), normal or near-normal LV size, normal LV ejection fraction, marked diastolic dysfunction (restrictive filling pattern), thickened ventricular walls (especially if amyloidosis/infiltration)
• Real-time strain imaging: Detects subclinical dysfunction; increasingly used for prognostication

• Superior tissue characterization: Late gadolinium enhancement

Immediate stabilization

• Decompensated DCM: IV loop diuretic (furosemide) for congestion; inotrope (dobutamine or milrinone) only for cardiogenic shock with hypoperfusion. Per the 2022 AHA/ACC/HFSA heart failure guideline, routine inotropes worsen mortality.
• Obstructive HCM with hypotension/syncope: give IV fluids and a pure vasoconstrictor (phenylephrine); inotropes and vasodilators worsen the dynamic gradient.

Dilated cardiomyopathy / HFrEF — first-line (four pillars of GDMT, 2022 AHA/ACC/HFSA)

• ARNI (sacubitril/valsartan), or ACEI/ARB if ARNI not tolerated — blocks RAAS-driven remodeling.
• Beta blocker: carvedilol, metoprolol succinate, or bisoprolol — reverses catecholamine toxicity.
• MRA: spironolactone or eplerenone — antifibrotic.
• SGLT2 inhibitor: dapagliflozin or empagliflozin, regardless of diabetes status.
• Escalation: hydralazine/isosorbide dinitrate in self-identified Black patients, ivabradine, vericiguat; CRT for LBBB with wide QRS; ICD for EF ≤35% after ≥3 months of GDMT; anticoagulation for AF or LV thrombus. Definitive: LVAD or transplantation.
• Remove the insult: alcohol abstinence, stop the cardiotoxic agent, treat thyroid/thiamine deficiency, rate-control tachycardia.

Hypertrophic cardiomyopathy (AHA/ACC HCM guideline)

• First-line for obstructive symptoms: non-vasodilating beta blocker; if intolerant, verapamil or diltiazem (negative inotropy prolongs filling and lowers the gradient).
• Second-line: add disopyramide, or a cardiac myosin inhibitor (mavacamten) with mandated serial EF monitoring.
• Definitive: septal reduction — surgical myectomy (preferred, especially if young or concomitant mitral disease) or alcohol septal ablation. ICD for high SCD risk (prior arrest, massive wall thickness, unexplained syncope, apical aneurysm, extensive LGE, family history of SCD).
• Contraindicated in obstructive HCM: nitrates, dihydropyridine CCBs, ACEI/ARB, digoxin, aggressive diuresis, and dehydration — all reduce preload/afterload and worsen obstruction.

Emergencies

• Sudden cardiac death: scar and myocyte disarray create reentry; the arrest rhythm is ventricular fibrillation / pulseless VT — shockable, so defibrillate immediately. Signaled beforehand by exertional syncope, nonsustained VT on monitoring, or an aborted arrest.
• Cardiogenic shock: falling cardiac output despite congestion — cool extremities, narrow pulse pressure, rising lactate; fulminant myocarditis and peripartum cardiomyopathy are classic settings.
• Cardiac tamponade is not a feature of cardiomyopathy but of pericardial disease — pulsus paradoxus and electrical alternans point away from restrictive cardiomyopathy toward effusion.
• Complete AV block, especially in cardiac sarcoidosis or amyloid, and after alcohol septal ablation (RBBB is expected; complete block may need a permanent pacemaker).

Disease complications

• Atrial fibrillation: atrial stretch/fibrosis; poorly tolerated in HCM and restrictive disease because loss of atrial kick collapses filling of a stiff ventricle — abrupt dyspnea or syncope.
• Thromboembolism: stasis in a dilated akinetic ventricle or fibrillating atrium → mural thrombus, stroke, or arterial embolus. Chagas and Löffler apical aneurysms are high-risk.
• Functional mitral regurgitation: annular dilation in DCM, or systolic anterior motion in HCM — holosystolic murmur with worsening congestion.
• Progressive heart failure and cardiorenal/cardiohepatic injury: rising creatinine, ascites, cardiac cirrhosis.
• Infective endocarditis risk with turbulent LVOT flow in HCM.

Treatment complications

• Disopyramide: anticholinergic dry mouth/urinary retention and QT prolongation.
• Mavacamten: excessive myosin inhibition → systolic dysfunction and heart failure.
• Myectomy: iatrogenic VSD, LBBB, aortic regurgitation.
• ICD: inappropriate shocks, lead infection, pocket hematoma.
• MRA: hyperkalemia; ARNI: hypotension and angioedema; SGLT2 inhibitor: euglycemic DKA and genital mycotic infection; digoxin: toxicity, amplified in amyloid.

• **Exertional syncope in a young athlete with a crescendo–decrescendo murmur that *loudens with Valsalva* → HCM. Best next step is a transthoracic echocardiogram**, not stress testing or catheterization; then screen first-degree relatives with ECG and echo (AHA/ACC HCM guideline).
• HCM vs aortic stenosis: HCM gives a brisk, bifid ("spike-and-dome") carotid pulse and no radiation to the carotids; AS gives pulsus parvus et tardus with radiation. Handgrip and squatting (↑afterload/preload) soften the HCM murmur but intensify MR and VSD murmurs.
• An ICD, not a drug, prevents sudden death in HCM. Beta blockers relieve symptoms but do not lower SCD risk — the classic distractor.
• Nitroglycerin for "anginal" chest pain in HOCM is the trap: preload reduction worsens obstruction and can precipitate syncope. Same logic condemns dihydropyridines, ACEI, and brisk diuresis.
• Low-voltage or pseudoinfarct ECG with thick ventricular walls (voltage–mass mismatch) plus apical-sparing ("cherry-on-top") strain and biatrial enlargement = cardiac amyloidosis. Confirm ATTR with technetium pyrophosphate scintigraphy after excluding a monoclonal protein; tafamidis stabilizes transthyretin.
• Restrictive cardiomyopathy vs constrictive pericarditis: Kussmaul sign and a pericardial knock with a calcified pericardium favor constriction (surgically curable by pericardiectomy); discordant respiratory ventricular pressures on catheterization also favor constriction. Do not answer tamponade — that requires pulsus paradoxus and an effusion.
• HFrEF from DCM is treated with four classes, not three: ARNI (or ACEI/ARB), beta blocker, MRA, and SGLT2 inhibitor (2022 AHA/ACC/HFSA) — layer them, then reassess EF before ICD placement.
• Named one-liners: apical ballooning after emotional stress = takotsubo (supportive care, usually recovers); apical aneurysm with RBBB in a Latin American immigrant = Chagas; bronzed skin, diabetes, arthropathy = hemochromatosis; young patient with heart block and hilar adenopathy = cardiac sarcoid.