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Dilated Cardiomyopathies

Chapter 269 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 269

Key Clinical Points

  1. Alcoholic cardiomyopathy requires cessation of alcohol; threshold is 3–4 ounces (≥60–80 g) of pure ethanol daily for ≥5 years, though women may develop it with lower amounts.
  2. Peripartum cardiomyopathy (PPCM) recovery to LVEF ≥0.50 occurs in 50–80% of cases within 6 months; recovery is less likely if LVEF <0.35 or marked dilation is present.
  3. Anthracycline cardiotoxicity management includes beta-adrenergic blockade and RAAS inhibition; dexrazoxane may prevent toxicity, but consensus on timing is lacking.
  4. Takotsubo syndrome (stress-induced cardiomyopathy) typically resolves within days to weeks; recurrence occurs in 10% of patients at an estimated rate of 2%/year.
  5. Checkpoint inhibitor myocarditis requires immediate high-dose glucocorticoids; outcomes are improving with earlier recognition and therapy.
  6. Hemochromatosis diagnosis is made primarily by MRI iron quantitation; phlebotomy is the management for early disease to remove iron.
  7. Trastuzumab cardiomyopathy may persist in about a third of affected patients and can progress to clinical heart failure and death.
  8. PPCM anticoagulation is typically prescribed for the first 6 weeks postpartum if LVEF <0.35 or marked dilation is present due to thrombus risk.
  9. TTN truncating mutations are found in ~15% of PPCM cases and are associated with lower rates of recovered systolic function.
  10. Vaccine-induced myocarditis risk after COVID-19 vaccines is estimated at 1/100,000 doses, increasing to 2–3/100,000 for recipients aged 18–39 years.

1. DEFINITION & OVERVIEW

• Definition: Dilated cardiomyopathy (DCM) is characterized by decreased left ventricular systolic function, typically with increased left ventricular dimensions, although dilation may be minimal in some cases. • Pathophysiology of Progression: ◦ Myocyte death occurs early; remaining myocytes develop hypertrophy in response to increased wall stress. ◦ Neurohormonal factors stimulate deleterious secondary responses contributing to disease progression. ◦ Dynamic remodeling of the interstitial scaffolding affects diastolic function and ventricular dilation. • Complications of Dilation: ◦ Mitral regurgitation: Commonly develops as the ventricle dilates and the valvular apparatus is distorted; often moderate to severe in advanced heart failure. ◦ Right Ventricular (RV) Involvement: May result from initial injury or later due to secondary pulmonary hypertension and mechanical interactions with the failing LV. • Recovery Potential: ◦ Approximately one-third of patients with recent-onset cardiomyopathy (absent coronary artery disease) show substantial spontaneous recovery to normal ejection fraction. ◦ Partial recovery to LVEF >0.40 is common in chronic DCM during therapy with neurohormonal modulation, cardiac resynchronization therapy for left bundle branch block, and diuretics.

2. EPIDEMIOLOGY

• Alcohol-Related Epidemiology: ◦ Prevalence: Similar between men and women with alcoholism. ◦ Clinical Presentation: Significantly more hospital admissions in men than women. ◦ Detection: LV dysfunction found in ~1/3 of asymptomatic patients with alcoholism. ◦ Threshold for Cardiomyopathy: 3–4 ounces (≥60–80 g) of pure ethanol daily for ≥5 years; women may develop it with lower amounts. ◦ Binge drinking: Frequent binge drinking may be sufficient to cause cardiomyopathy. • Peripartum Cardiomyopathy (PPCM) Epidemiology: ◦ Incidence: 1:1000 to 1:4000 deliveries in the United States. ◦ Risk Factors: Fourfold higher risk in black women; recovery of normal LVEF is slower and less likely in black women than white women. ◦ Mortality: One-year mortality rates range from 4% to 11% in the US; up to twofold higher in Africa.

3. ETIOLOGY & PATHOPHYSIOLOGY

• General Etiology: ◦ Multiple causes including myocarditis, genetic variants, toxic agents, and metabolic disorders (Table 269-1). • Inflammatory Myocarditis: ◦ Infective: Viral (coxsackie, adenovirus, COVID-19, HIV); Parasitic (Trypanosoma cruzi—Chagas' disease, trypanosomiasis, toxoplasmosis); Bacterial (diphtheria); Spirochetal (Borrelia burgdorferi—Lyme disease); Rickettsial (Q fever); Fungal. ◦ Noninfective: Granulomatous inflammatory disease; Sarcoidosis; Giant cell myocarditis; Eosinophilic myocarditis; Polymyositis, dermatomyositis; Collagen vascular disease; Checkpoint inhibitor chemotherapy; Transplant rejection. • Toxic Causes: ◦ Alcohol; Catecholamines (amphetamines, cocaine); Chemotherapeutic agents (anthracyclines, trastuzumab); Interferon; Other therapeutic agents (hydroxychloroquine, chloroquine); Drugs of misuse (testosterone and other anabolic steroids, emetine); Heavy metals (lead, mercury); Occupational exposure (hydrocarbons, arsenicals). • Metabolic Causes: ◦ Nutritional deficiencies: thiamine, selenium, carnitine. ◦ Electrolyte deficiencies: calcium, phosphate, magnesium. ◦ Endocrinopathy: Thyroid disease, Pheochromocytoma, Diabetes mellitus, Obesity, Hemochromatosis. ◦ Inherited metabolic pathway defects; Familial cardiomyopathies. • Miscellaneous Causes: ◦ Arrhythmogenic ventricular cardiomyopathy; Peripartum cardiomyopathy; Left ventricular noncompaction; Tachycardia-related cardiomyopathy; Supraventricular arrhythmias with uncontrolled rate; High burden of premature ventricular complexes or NSVT.

4. CLINICAL FEATURES

• General Presentation: ◦ Pulmonary edema, hypotension, and chest pain with ECG changes mimicking acute infarction. ◦ LV dysfunction extends beyond a specific coronary artery distribution; typically resolves in days to weeks (in Takotsubo). • Peripartum Cardiomyopathy (PPCM): ◦ Timing: Most cases present within the first week after delivery. ◦ Symptoms: Increasing edema and dyspnea as urine output fails to keep up with fluid mobilization. ◦ Complications: Risk of pulmonary emboli or coronary artery dissection must be excluded. • Takotsubo Syndrome: ◦ Presentation: Often triggered by intense emotional/physical stress; characterized by apical ballooning. ◦ Resolution: Dysfunction typically resolves within days to weeks. • Metabolic & Nutritional Conditions: ◦ Beriberi (Thiamine): Thiamine deficiency → heart failure; prompt recovery with thiamine repletion. ◦ Carnitine: Abnormalities cause dilated/restrictive cardiomyopathy (common in children). ◦ Selenium: Deficiency causes Keshan's disease. ◦ Calcium: Chronic deficiency (e.g., hypoparathyroidism) → severe heart failure; responds to calcium repletion. ◦ Phosphate: Hypophosphatemia during starvation or early refeeding. ◦ Obesity: Associated with impaired excretion of volume load; weight reduction often improves EF. • Special Conditions: ◦ Pheochromocytoma: Often presents with postural hypotension; requires alpha-adrenergic receptor antagonists and surgical extirpation. ◦ Renal Artery Stenosis: High renin states → modest depression in ejection fraction with little or no ventricular dilation; manifests as flash pulmonary edema due to sudden shifts in vascular tone.

5. DIFFERENTIAL DIAGNOSIS

• Alcohol vs. Genetic Cardiomyopathy: ◦ Alcohol cardiomyopathy is a diagnosis of exclusion. ◦ Note: TTN truncating mutations found in ~15% of patients with presumed alcohol cardiomyopathy. • Takotsubo vs. Acute MI: ◦ Distinction: Takotsubo resolves in days/weeks; MI does not. ◦ Distribution: Takotsubo dysfunction extends beyond a single coronary artery distribution. ◦ Rule-out: Coronary angiography required to rule out acute coronary occlusion. • Hemochromatosis: ◦ Identification: Systemic iron overload causing cardiac siderosis. ◦ Differentiation: Distinguished from other cardiomyopathies by MRI iron quantitation.

6. DIAGNOSTIC APPROACH

  1. General Diagnostic Pathway: ◦ Echocardiography: Initial assessment of LVEF and myocardial dimension. ◦ Coronary Angiography: Performed if Takotsubo is suspected to rule out acute coronary occlusion. ◦ Cardiac MRI: Used for quantifying iron stores (Hemochromatosis) or identifying apical ballooning/edema (Takotsubo). ◦ Genetic Testing: Consider for TTN mutations in PPCM cases.
  2. Specific Diagnostic Criteria: ◦ PPCM:
  3. Clinical presentation of heart failure/congestion within first week post-delivery.
  4. Assessment of LVEF and myocardial dilation. ◦ Hemochromatosis:
  5. MRI iron quantitation (primary diagnostic modality). ◦ Takotsubo Syndrome:
  6. ECG changes mimicking infarction.

  7. Cardiac MRI showing apical ballooning/edema without necrosis.

  8. General Management of DCM: ◦ Guideline-directed medical therapies (GDMT). ◦ Beta-adrenergic antagonists. ◦ Mineralocorticoid receptor antagonists. ◦ Diuretics for fluid management. ◦ Electrolyte repletion.

  9. Specific Management Protocols: ◦ Anthracycline Cardiotoxicity:
  10. Beta-adrenergic blockade.
  11. RAAS inhibition. ◦ Peripartum Cardiomyopathy (PPCM):
  12. Anticoagulation: Prescribed for first 6 weeks postpartum if LVEF <0.35 or marked dilation is present. ◦ Takotsubo Syndrome:
  13. Supportive management; resolution typically occurs in days to weeks. ◦ Hemochromatosis:
  14. Phlebotomy: Primary management for early disease to remove iron. ◦ Pheochromocytoma:
  15. Alpha-adrenergic receptor antagonists.
  16. Surgical extirpation (definitive therapy).

8. PROGNOSIS & COMPLICATIONS

• PPCM Prognosis: ◦ Recovery to LVEF ≥0.50: 50–80% of cases within 6 months. ◦ Risk Factors for Poor Recovery: LVEF <0.35 at 6 weeks post-delivery; TTN truncating mutations. • Takotsubo Prognosis: ◦ Resolution: Typically occurs in days to weeks. ◦ Recurrence: ~10% of patients (estimated rate of 2%/year). • Hemochromatosis Progression: ◦ Can progress to clinical heart failure and death if not managed.

9. SPECIAL CONSIDERATIONS

• Pregnancy & Breastfeeding: ◦ PPCM: Requires exclusion of pulmonary emboli and coronary artery dissection. • Pediatric Considerations: ◦ Carnitine metabolism defects (dilated/restrictive cardiomyopathy). ◦ Selenium deficiency (Keshan's disease). • Nutritional Deficiencies: ◦ Beriberi (Thiamine): High-output to low-output progression; prompt recovery with thiamine. ◦ Calcium: Severe heart failure in hypoparathyroidism or intestinal dysfunction; responds to calcium repletion. ◦ Phosphate: Hypophosphatemia during starvation/refeeding.

10. KEY PEARLS & CLINICAL TRAPS

• Alcohol Threshold: 3–4 oz (≥60–80 g) daily for ≥5 years is the standard metric. ◦ Note: Women may develop cardiomyopathy with lower amounts. ◦ Note: Frequent binge drinking may be sufficient. • Takotsubo Distinction: Look for apical ballooning and resolution within weeks to differentiate from MI. ◦ Recurrence rate: 10% of patients (2%/year). • Hemochromatosis Diagnosis: Primarily MRI; phlebotomy is the management for early disease. • PPCM Timing: Most cases present within the first week after delivery. ◦ Anticoagulation threshold: LVEF <0.35 or marked dilation. • Checkpoint Inhibitors: Require immediate high-dose glucocorticoids for myocarditis. • Vaccine Myocarditis: Risk is 1/100,000 (general) and 2–3/100,000 (ages 18–39).

Reference Tables

TABLE 269-1 Major Causes of Dilated Cardiomyopathy (with Common Examples) Inflammatory Myocarditis (see Chap. 268)…

Harrison's 22e, p.2016

  • Inflammatory Myocarditis (see Chap. 268)
  • Infective
  • Viral (coxsackie,a adenovirus,a COVID-19, HIV)
  • Parasitic (Trypanosoma cruzi—Chagas’ disease, trypanosomiasis,
    toxoplasmosis)
  • Bacterial (diphtheria)
  • Spirochetal (Borrelia burgdorferi—Lyme disease)
  • Rickettsial (Q fever)
  • Fungal (with systemic infection)
  • Noninfective
  • Granulomatous inflammatory disease
  • Sarcoidosis
  • Giant cell myocarditis
  • Eosinophilic myocarditis
  • Polymyositis, dermatomyositis
  • Collagen vascular disease
  • Checkpoint inhibitor chemotherapy
  • Transplant rejection
  • Toxic
  • Alcohol
  • Catecholamines: amphetamines, cocaine
  • Chemotherapeutic agents (anthracyclines, trastuzumab)
  • Interferon
  • Other therapeutic agents (hydroxychloroquine, chloroquine)
  • Drugs of misuse (testosterone and other anabolic steroids emetine)
  • Heavy metals: lead, mercury
  • Occupational exposure: hydrocarbons, arsenicals
  • Metabolica
  • Nutritional deficiencies: thiamine, selenium, carnitine
  • Electrolyte deficiencies: calcium, phosphate, magnesium
  • Endocrinopathy
  • Thyroid disease
  • Pheochromocytoma
  • Diabetes mellitus
  • Obesity
  • Hemochromatosis
    Inherited metabolic pathway defects (see Chap. 267)
  • Familiala (see Table 267-1)
  • Cardiomyopathies without extracardiac involvement
    Cardiomyopathy with skeletal myopathy, for example:
  • Dystrophin-related dystrophy (Duchenne’s, Becker’s)
  • Mitochondrial myopathies (e.g., Kearns-Sayre syndrome)
  • Hemochromatosis
  • Susceptibility to immune-mediated myocarditis
    Associated with other systemic diseases
  • Miscellaneous (Shared Elements of Above Etiologies)
  • Arrhythmogenic ventricular cardiomyopathy
    Peripartum cardiomyopathy
  • Left ventricular noncompactiona
  • Tachycardia-related cardiomyopathy
  • Supraventricular arrhythmias with uncontrolled rate
  • Very frequent nonsustained ventricular tachycardia or high burden of
    premature ventricular complexes