Approach
Cardiomyopathy is diagnosed by taking an accurate clinical history, including family history (3-generational pedigree) and clinical examination, followed by appropriate investigations. Laboratory findings vary depending on specific the etiology. A 12 lead ECG and echocardiogram will detect most cardiomyopathies. Further evaluation may include more complex ECG testing, additional imaging (e.g., chest radiography, cardiac MRI, cardiac CT), cardiac catheterization, endomyocardial biopsy, and genetic testing.[5] These tests are often nonspecific, pointing only to the pathophysiologic consequences of cardiomyopathy rather than its specific etiology. A combination of all these modalities is typically required to determine the etiology, as no single available test is usually specific enough to determine the cause.
History
The clinical history is a critical component in the diagnosis of cardiomyopathies. Emphasis should be placed on risk factors for specific causes. Medical illnesses, family history, and alcohol and drug exposure may predispose to the development of cardiomyopathies.
History of present illness
The most common symptoms associated with cardiomyopathy are dyspnea, chest discomfort, palpitations, and syncope.
Patients with concerning cardiac symptoms such as exertional chest pain, syncope, sustained palpitations, orthopnea, paroxysmal nocturnal dyspnea, and those with a family history of cardiomyopathy or premature cardiac death should be referred for specialist investigation.[5]
Medical history
History of coronary artery disease (CAD) and subsequent cardiac ischemia should be excluded.
History of any causes of secondary cardiomyopathies should be addressed, including infiltrative, storage, toxic, endomyocardial, inflammatory, endocrine, cardiofacial, and neuromuscular/neurologic causes; nutritional deficiencies; autoimmune or collagen diseases; electrolyte imbalance; and exposure to chemotherapeutic agents.[1]
Family history
Family history of premature cardiac death or arrhythmia may indicate risk of primary cardiomyopathy. Specific questions may elucidate hereditary causes of secondary cardiomyopathy including infiltrative diseases (familial autosomal dominant amyloidosis, Gaucher, Hunter, Hurler), storage diseases (Fabry, glycogen storage, Niemann-Pick), Noonan syndrome, lentiginosis, Friedreich ataxia, Duchenne/Becker muscular dystrophy, Emery-Dreifuss muscular dystrophy, myotonic dystrophy, neurofibromatosis, and tuberous sclerosis.[1]
Physical exam
No specific physical examination findings are consistent with a particular cause; the examination is directed towards seeking signs of cardiac dysfunction. A sustained prominent apical impulse on palpation may suggest left ventricular hypertrophy. A diffusely palpable cardiac impulse with apical displacement may be seen with ventricular dilatation. Auscultation of the heart may reveal murmurs, an S4 gallop (heard in types of cardiomyopathy that involve increased left ventricular pressure) or an S3 gallop (heard when there is increased left ventricular volume).
Auscultation sounds: Third heart sound gallop
Auscultation sounds: Fourth heart sound gallop
Auscultation of the lungs may demonstrate crackles, indicating pulmonary congestion. Pedal and leg edema, and jugular venous distension, may also be present in certain cardiomyopathies. Specialist referral is indicated if any of the following features are present: an ejection systolic murmur (in left ventricular outflow tract obstruction, as seen in hypertrophic cardiomyopathy, this increases in intensity with the Valsalva manoeuvre and is diminished by squatting); peripheral and/or pulmonary edema; elevated jugular venous pressure; an irregular pulse.[5]
Initial tests
An ECG, although commonly nonspecific, may show abnormalities that point to an individual etiology. A normal ECG has, approximately, a 98% negative predictive value when systolic dysfunction is suspected.[79]
Initial laboratory tests should include baseline blood tests such as CBC, metabolic panel, and thyroid function in all patients to exclude contributory or exacerbating factors. A B-type natriuretic peptide (BNP) provides supporting data in patients with dyspnea. Patients presenting with chest pain require measurement of cardiac markers including troponins. In addition, a chest x-ray is recommended.
Echocardiogram, other imaging, and cardiac catheterization
Echocardiography is an extremely useful and noninvasive diagnostic tool.[13] An echocardiogram helps to distinguish the cardiomyopathies with respect to pathophysiology. It can differentiate between hypertrophic, restrictive, or dilated cardiomyopathies in most cases. It may suggest a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) or athlete's heart. The British Society of Echocardiography has outlined recommendations for assessment and diagnosis of dilated cardiomyopathy by echocardiogram.[80]
Cardiac MRI is a useful method for uncovering the etiology of cardiomyopathy because it provides excellent contrast and spatial resolution of the heart. It is also noninvasive, readily available, and not operator-dependent. MRI can be used to assess ventricular end-diastolic volumes, presence of intracardiac thrombi, stroke volume, ejection fraction, and valvular pathology. MRI also provides information on whether there is fibrosis or scar present in the cardiac muscle, which is seen as late gadolinium enhancement, and this helps with diagnosis and risk assessment in many cardiomyopathies.[8][81] Cardiac CT is particularly helpful in the assessment of possible concomitant coronary artery disease.[13] Multimodality imaging can be used to aid diagnosis and guide management in the majority of cardiomyopathies.[14]
Cardiac catheterization can be a useful additional test in some cases. Ventricular and atrial pressures are measured, which allow for the calculation of pressure gradients across cardiac valves and the left ventricular outflow tract. Catheterization of the heart allows for ventriculography to be performed. Ejection fraction, ventricular size and wall motion, and left ventricular outflow tract size can be estimated, and the presence of valvular regurgitation can be evaluated. Additionally, coronary angiography can be performed to evaluate for coronary arterial disease as a cause of ischemia.
It is very important to distinguish restrictive cardiomyopathy from constrictive pericarditis, as pericardiectomy is indicated for constrictive pericarditis. Tests including echocardiography, cardiac MRI, and cardiac catheterization are helpful in distinguishing between these two conditions.[82]
Endomyocardial biopsy
In very rare circumstances, an endomyocardial biopsy is needed to help differentiate disease processes and guide therapy. It may be useful in the diagnosis of certain types of cardiomyopathy (e.g., infiltrative), in particular where there has been a recent onset of severe heart failure.[45]
Specialized testing
Testing may be directed towards excluding possible causes of cardiomyopathy.
Many novel genes are reported to cause cardiomyopathy, and the genetic evaluation of cardiomyopathy is becoming more feasible because of increasing availability of high-throughput gene sequencing technologies.[83] Genetic testing may be indicated to identify abnormalities in patients with conduction system disorders, lysosomal storage diseases, or Noonan syndrome. Mitochondrial disorders may result from mutations in either mitochondrial DNA or nuclear DNA, and the inheritance pattern will therefore vary depending on location of the mutation.[84]
Serologies (e.g., Lyme, HIV, parvovirus) may indicate a cause of myocarditis.
Liver function tests and a coagulation profile: may indicate dysfunction in alcohol-related cardiomyopathy or hemochromatosis.
Electrophysiologic studies may be required for conduction system disorders or Brugada syndrome. A drug provocation test using a sodium channel blocker may unmask ECG findings in these syndromes.[85]
Exercise tolerance testing, ambulatory monitoring, or signal-averaged ECG may help diagnose ARVC.
Serum iron studies may indicate systemic iron overload (hemochromatosis) or deficiency (anemia). Levels of vitamins or selenium may be low in systemic deficiencies.
Alpha-galactosidase A levels are low in Fabry disease. These levels can be normal in affected females due to the sex-linked inheritance pattern of the disease. Therefore, genetic testing may be necessary in females if there is clinical suspicion of Fabry’s disease.
Endocrinologic tests are required for suspected diabetes mellitus (elevated fasting blood sugar and/or HbA1c); thyroid dysfunction (abnormal thyroid-stimulating hormone and levels of thyroid hormones); or acromegaly (high insulin-like growth factor-1 and lack of glucose suppression of growth hormone levels).
Serum antinuclear antibodies are usually positive in systemic lupus erythematosus.
A trial of thiamine is indicated for suspected deficiency (wet beriberi).
Muscle biopsy may be used for diagnosis of mitochondrial diseases.
Serum protein electrophoresis (SPEP) or tissue (e.g., rectal) biopsy may indicated for suspected amyloidosis.
Pulmonary function testing, lung or lymph node biopsy (noncaseating granulomas), and measurement of angiotensin-converting enzyme (high) may support a diagnosis of sarcoid.
Nuclear imaging modalities (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) may be considered for the evaluation of specific infiltrative cardiomyopathies, including cardiac sarcoidosis.[59]
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