Cardiomyopathy

Background

• Cardiomyopathy is broadly defined as a disease of the myocardium not due to coronary artery disease, hypertension, valvular disease, or congenital heart disease.
• Multiple cardiomyopathy definitions and classification schemes exist, and there is no consensus on which is most accurate; classification systems more recently proposed include MOGE(S), European Society of Cardiology (ESC), and American Heart Association (AHA) classification systems
  • MOGE(S) classification system (endorsed by World Heart Federation)
    • Cardiomyopathies are defined as disorders characterized by morphologically and functionally abnormal myocardium in absence of any disease sufficient to cause the observed phenotype.
    • MOGE(S) classification system groups cardiomyopathies by multiple identifiers, including:
      • M - morphofunctional phenotype
      • O - organ involvement
      • G - genetic inheritance
      • E - etiologic annotation, including genetic defect or underlying disease/substrate
      • S (optional) - functional status of disease may be described using American College of Cardiology/American Heart Association (ACC/AHA) stage A-D or New York Heart Association (NYHA) functional class
  • ESC classification system
    • Cardiomyopathy is defined as a myocardial disorder characterized by structurally and functionally abnormal cardiac function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to cause observed myocardial abnormality.
    • The ESC working group on myocardial and pericardial diseases cardiomyopathy classification system groups cardiomyopathies by morphological and functional phenotypes.
      • Cardiomyopathy morphological and functional phenotypes include:
        • hypertrophic cardiomyopathy
        • dilated cardiomyopathy
        • arrhythmogenic right ventricular dysplasia
        • restrictive cardiomyopathy
        • unclassified, such as left ventricular noncompaction and takotsubo syndrome
      • Cardiomyopathies subclassified by familial/genetic and nonfamilial/nongenetic forms:
        • familial/genetic forms include unidentified gene defects and disease subtype genetic mutations
        • nonfamilial/nongenetic forms include idiopathic and disease subtypes
      • Inherited arrhythmia syndromes are not classified as cardiomyopathies.
  • AHA classification system:
    • Cardiomyopathies are defined as a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction and usually involve ventricular hypertrophy and/or dilatation.
    • The AHA classification system groups cardiomyopathies by predominant organ involvement.
      • Primary cardiomyopathies involve only the heart or predominantly involve the heart and include genetic, acquired, and mixed forms.
      • Secondary cardiomyopathies involve the myocardium as part of a larger number and variety of generalized systemic or multiorgan disorders, including systemic disorders, hemochromatosis, sarcoidosis, autoimmune/collage vascular diseases, toxins, chemotherapeutics, and endocrine disorders.

Table 1. AHA Types of Primary Cardiomyopathies

Evaluation

• Evaluation typically includes a combination of cardiac evaluation, noncardiac evaluation, and molecular evaluation for specific diagnoses.
• The Initial testing typically includes the following:
  • history and physical
  • electrocardiography (ECG)
  • blood tests, including creatinine clearance, renal function tests, liver function tests, complete blood count, plasma transferrin saturation, serum ferritin, and biomarkers (B-type natriuretic peptide [BNP], N-terminal pro-brain natriuretic peptide [NT-proBNP], and high sensitivity troponin T [hsTnT])
  • chest x-ray
• Echocardiography is typically performed after initial testing to assess the cardiac structure and function and to evaluate for specific etiologies.
• Additional evaluation to exclude secondary causes of heart failure typically includes the following:
  • coronary angiography or computed tomography coronary angiography to exclude coronary artery disease
  • blood pressure measurement and targeted history to exclude hypertensive heart disease
  • echocardiography (above) usually starts with transthoracic echocardiography (TTE); occasionally transesophageal echocardiography (TEE) may be needed if image quality of TTE is inadequate or inconclusive
• Additional testing may be directed at suspected etiologies based on test findings:
  • cardiac magnetic resonance imaging (MRI) is usually appropriate in patients with suspected cardiomyopathy to evaluate cardiac function and morphology and can provide comprehensive assessment of myocardial structure and associated pathology
  • for patients with heart failure with reduced ejection fraction (left ventricular ejection fraction [LVEF] < 40%) or midrange ejection fraction (LVEF 40%-49%), additional testing for suspected dilated cardiomyopathy may include the following:
    • cardiac MRI to assess ventricular structure and function and characterize cardiac tissue
    • genetic testing to evaluate for familial disease
    • testing to evaluate for infectious causes, such as blood tests for HIV or Chagas disease, polymerase chain reaction (PCR), or endomyocardial biopsy
    • blood tests to evaluate for autoimmune disorders, including rheumatoid factor, C-reactive protein (CRP) level, and specific serology for extracardiac involvement
    • toxicology to evaluate for toxins, including alcohol levels, anabolic steroids, and heavy metals
    • endocrine/metabolic evaluation, including thyroid function tests, growth hormone, insulin-like growth factor-1 (IGF-1) to evaluate for acromegaly, and urine and serum catecholamines to evaluate for pheochromocytoma
    • nutrient levels to evaluate for nutritional deficiencies, including thiamine deficiency (may suggest alcohol abuse), carnitine deficiency, niacin deficiency, and selenium deficiency
  • for patients with heart failure with preserved ejection fraction (LVEF ≥ 50%) and normal ventricular wall thickness, additional testing for suspected restrictive cardiomyopathy may include the following:
    • cardiac MRI to assess ventricular structure and function and characterize cardiac tissue
    • evaluation for cardiac amyloidosis, including blood and urine electrophoresis and immunofixation, serum free light chain assay, fat aspiration/biopsy, scintigraphy with technetium-99m 3, 3-diphosphono-1, 2-propanodicarboxylic acid (99mTc-DPD), hydroxymethylene diphosphonate (HMDP), or pyrophosphate (PYP), endomyocardial biopsy, and transthyretin sequencing
    • evaluation for cardiac sarcoidosis, including fluorodeoxyglucose positron emission tomography (FDG PET)-scintigraphy
    • evaluation for iron overload and hemochromatosis, including plasma transferrin saturation, serum ferritin, hemoglobin electrophoresis, and genetic testing
  • for patients with heart failure with preserved ejection fraction (LVEF ≥ 50%) and increased wall thickness, additional testing for suspect hypertrophic cardiomyopathy or restrictive cardiomyopathy may include the following:
    • cardiac MRI to assess ventricular structure and function and characterize cardiac tissue
    • evaluation for Fabry disease, including alpha-galactosidase A and genetic testing
    • evaluation for mitochondrial disorder with lactic acid
    • evaluation for cardiac amyloidosis, including blood and urine electrophoresis and immunofixation, serum free light chain assay, fat aspiration/biopsy, scintigraphy with 99mTc-DPD, HMDP, or PYP, endomyocardial biopsy, and transthyretin sequencing
    • evaluation for cardiac sarcoidosis, including FDG PET-scintigraphy
    • evaluation for iron overload and hemochromatosis, including plasma transferrin saturation, serum ferritin, hemoglobin electrophoresis, genetic testing, and cardiac magnetic resonance imaging

Management

• Management of symptomatic heart failure typically includes guideline-directed medical therapy; see also
  • Heart Failure With Reduced Ejection Fraction (HFrEF)
  • Heart Failure With Preserved Ejection Fraction (HFpEF)
  • Heart Failure With Mildly Reduced Ejection Fraction (HFmrEF)
• For management of specific primary cardiomyopathies, see also
  • Dilated Cardiomyopathy
  • Hypertrophic Cardiomyopathy
  • Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
  • Left Ventricular Noncompaction
  • Restrictive Cardiomyopathy
  • Myocarditis
  • Takotsubo Syndrome
  • Peripartum Cardiomyopathy
  • Tachycardia-induced Cardiomyopathy
  • Inherited Arrhythmia Syndromes
• Management of secondary cardiomyopathies primarily involves removing or treating extracardiac disease and treating heart failure symptoms.