- Clinical science
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy. Although most cases are idiopathic, a number of conditions (e.g., coronary artery disease, wet beriberi), infections (e.g., Coxsackie B virus, Chagas disease), and substances (e.g., heavy drinking, cocaine) have been identified as causes. In DCM, the decreased ventricular contractility of the dilated left ventricle (LV) leads to failure of the left and eventually right heart with decreased ventricular output. Isolated dilation and subsequent decrease in contractility of right ventricle (RV) is rare. Dilation can be seen on echocardiography, the most important diagnostic tool for all cardiomyopathies. Therapy involves management of congestive heart failure and treatment of the underlying condition.
Hypertrophic cardiomyopathy (HCM) is the second most common cardiomyopathy. There are two types of HCM: The nonobstructive type is characterized by a thickening of the LV wall and is often asymptomatic, although arrhythmias and even sudden cardiac death can occur. The obstructive type (HOCM) is characterized by a thickening of the interventricular septum and systolic anterior movements of the mitral valve, causing LV outflow obstruction. Both types manifests with signs of reduced blood flow (dyspnea, dizziness, syncope) and are diagnosed with echocardiography. Even if most individuals are asymptomatic, it is important that they avoid strenuous exercise. Symptomatic patients should be treated with beta blockers.
Restrictive cardiomyopathy (RCM) is caused by the proliferation of connective tissue, with subsequent atrial enlargement (but normal ventricles). Like DCM, RCM causes left and right heart failure. The ejection fraction is usually normal, but diastolic filling is reduced on echocardiography. While a number of drugs offer symptomatic relief, the overall prognosis remains poor.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) primarily affects the right ventricle and is characterized by fibrofatty replacement of myocardium, which causes myocardial thinning and subsequent ventricular dilation. Although the hallmark finding is arrhythmia, symptoms are highly variable. Because management depends greatly on individual factors, such as the extent of the disease, there is no single best course of treatment. All patients should avoid strenuous exercise.
Arrhythmia-induced cardiomyopathy is a very rare type of cardiomyopathy. It is caused by long-standing arrhythmia and typically affects the left ventricle. Features include palpitations, syncope, and signs of arrhythmia on ECG. Progression to left heart failure is possible in severe cases. Treatment involves antiarrhythmics such as beta blockers for rhythmic control.
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- Incidence: 6/100,000 per year (most common cardiomyopathy)
- Sex: ♂ > ♀ (approx. 3:1)
- Idiopathic (∼ 50%)
- Genetic predisposition 
- Coronary heart disease (ischemic cardiomyopathy)
- Arterial hypertension
- Peripartum cardiomyopathy (occurs in the last trimester or up to 6 months postpartum)
- Systemic lupus erythematosus; , sarcoidosis
- Toxic substances
- Chronic tachycardia (e.g., atrial fibrillation)
- Endocrinopathies (e.g., pheochromocytoma, acromegaly, hyperthyroidism)
- Valvular heart disease
To remember some high-yield secondary causes of dilated cardiomyopathy, think ABCCCDD: Alcohol use, Beriberi, Cocaine, Coxsackie B virus, Chagas, Doxorubicin/Daunorubicin
- Causative factors decrease the contractility of myocardium → compensatory mechanisms () are activated to maintain → ↑ end-diastolic volume (preload) → → eccentric hypertrophy (sarcomeres added in series) and dilation of the ventricle → reduced myocardial contractility → systolic dysfunction and ↓ ejection fraction → heart failure
↓ LV contractility due to dilation leads to and eventually
Left heart failure: decreased LV output leads to via the following mechanisms
- Diminished systemic perfusion → decreased perfusion of end organs → (e.g., renal/cerebral dysfunction, cold extremities)
- ↑ Pressure within the pulmonary circulation → pulmonary circulation congestion → impaired gas exchange and fluid extravasation into the interstitium and alveoli → with predominant pulmonary congestion (e.g., dyspnea, orthopnea, cardiac asthma)
- Right heart failure : decreased right ventricular output → systemic circulation congestion → with predominant systemic congestion (see )
- Left heart failure: decreased LV output leads to via the following mechanisms
- General symptoms: gradual development of CHF symptoms
- Physical examination findings
Diagnostic approach to DCM aims to:
- Investigate the underlying cause with confirming either the secondary cause or idiopathic disease
- Assess cardiac function
- Assess structural remodeling
- Specific investigations are guided by suspected underlying cause or complications
- Echocardiography: used mainly for assessment of cardiac remodeling and function as it has a limited role in establishing etiology
- Chest x-ray
- ECG: The following findings may be present but are not specific for DCM.
Histology (idiopathic DCM): mostly used to exclude other causes of cardiomyopathy
- Interstitial fibrosis without interstitial inflammation
- In particular, myocardial interstitial fibrosis is more extensive in the subendocardium because of its higher metabolic demand than the subepicardial layer.
- Variation in the caliber of cardiomyocytes: cells may appear elongated and wavy with hypertrophy
- Nuclear atypia
- Treatment of the underlying disease
- Treatment of heart failure
- Anticoagulation: in the case of mechanical valves, intraventricular thrombus and/or atrial fibrillation (e.g., warfarin)
- Surgical treatment
- Second most common cardiomyopathy
- Alongside myocarditis, HCM is one of the most frequent causes of sudden cardiac death in young patients, especially young athletes.
Primary HOCM: a genetic condition characterized by otherwise unexplained left ventricular hypertrophy.
- Most common hereditary heart disease; : (60–70% of HCM cases)
- Autosomal dominant inheritance with varying penetrance (familial occurrence in > 50% of cases)
- Most commonly due to mutations in genes encoding (e.g., myosin heavy chain, myosing binding protein C) → causes disorganized myocyte architecture characterized by myofibrillar disarray and fibrosis
- Less commonly due to a mutation in cardiac sarcomeric proteins such as troponin and tropomyosin
- Secondary HCM: : associated with certain conditions (e.g., chronic hypertension, Friedreich ataxia; , , , )
- Pressure related hypertrophy: Cardiac hypertrophy is caused by chronic pressure and volume overload.
Obstructive type (HOCM):
Greater hypertrophy of interventricular septum compared with the LV wall → obstruction of LV outflow 
- Concentric hypertrophy: increased, asymmetric LV wall thickness and decreased LV size, as sarcomeres are added in parallel
- During systole:
- Accelerated blood flow through ventricular outflow tract causes negative pressure (Venturi effect) → anterior leaflet of the mitral valve is drawn against the septum (systolic anterior motion, SAM) → ↑ outflow tract obstruction
- Ejection flow pushes against abnormally placed and elongated MV leaflets → creates drag forces on a portion of the mitral valve leaflets → the leaflets are dragged into the outflow tract → ↑ outflow tract obstruction
- Increasing mitral regurgitation
- Obstruction is exacerbated by factors that lead to increased heart contraction force and cardiac output ;:
- Greater hypertrophy of interventricular septum compared with the LV wall → obstruction of LV outflow 
Nonobstructive type involves hypertrophy of the left (possibly also the right) ventricle resulting in:
- Reduced diastolic compliance of the ventricle → reduced diastolic filling volume → reduced systolic output volume
- Impaired cardiac contractility with reduced systolic output → reduced peripheral and myocardial perfusion (myocardial ischemia) → can cause disruption of electrical impulses → cardiac arrhythmia
Clinical features 
- Symptoms: worsen with exercise, dehydration, and use of certain drugs (e.g., diuretics, hydralazine, ACEIs/ARBs, digoxin)
- Systolic ejection murmur (crescendo-decrescendo)
- Possible holosystolic murmur from mitral regurgitation
- Sustained apex beat
- S4 gallop
- Paradoxical split of S2
- Pulsus bisferiens: LV outflow obstruction causes a sudden quick rise of the pulse followed by a slower longer rise (biphasic pulse).
- ↑ LVOT pressure gradient via doppler echocardiography 
- Provocation tests (see below) are obligatory if no obstruction is discernible at rest.
- Can be normal
- Signs of left ventricular hypertrophy (see “Sokolow-Lyon criteria” in “Interpretation of the QRS complex” in )
- Possibly nonspecific ST-wave and/or T-wave changes
- Commonly in obstructive type: abnormally deep Q waves, particularly in the inferior (II, III, and aVF) and lateral (I, aVL, V4-6) leads
- Left bundle branch block
- Exercise testing
- Additional diagnostic procedures
- All patients should avoid strenuous exercise.
- Asymptomatic patients usually do not require further treatment.
- Symptomatic patients
- Medical therapy
- Interventional therapy:
- Surgery: myectomy (Morrow procedure)
Positive inotropic and afterload-reducing or preload-reducing drugs (e.g., digitalis, glyceryl trinitrate, calcium channel blockers of the dihydropyridine class, ACEIs) are contraindicated in patients with obstructive hypertrophic cardiomyopathy!
- Least common cardiomyopathy (accounts for ∼ 5% of all cardiomyopathies) 
- Systemic diseases (infiltrative cardiomyopathy)
- Löffler endocarditis: a condition characterized by eosinophilic infiltration of endocardium and myocardium occurring in diseases accompanied by eosinophilia 
- Endocardial fibroelastosis: a condition characterized by diffuse thickening of the left ventricular endocardium due to proliferation of fibrous and elastic tissue
- Endomyocardial fibrosis: a disorder with unknown etiology characterized by focal or diffuse endomyocardial thickening
- Iatrogenic causes of myocardial fibrosis
Remember the etiology of restrictive cardiomyopathy with “PLEASe Help!”: Postradiation/Postsurgery fibrosis, Löffler endocarditis, Endocardial fibroelastosis, Amyloidosis, Sarcoidosis, Hemochromatosis)
- Proliferation of connective tissue → ↓ elasticity of myocardium → ↓ ventricular compliance → ↓ diastolic filling → atrial congestion → atrial enlargement and severe diastolic dysfunction → systemic venous congestion
- Most common: dyspnea
- Symptoms of right heart failure
Less common features
- Possibly S4 heart sound
- See “Clinical features” in “ ”.
- CXR: or less commonly MRI
- Cardiac catheterization
- Endo/myocardial biopsy
- Treatment is generally limited and often palliative.
- Treatment of underlying condition (e.g., phlebotomy for hemochromatosis)
- Symptomatic treatment
- Anticoagulation (e.g., warfarin) to prevent embolism in patients with a history of atrial fibrillation
- Heart transplant (in patients with refractory symptoms)
- Mutations of various genes (e.g., JUP gene)
- Autosomal recessive or autosomal dominant inheritance 
- Right ventricular myocardial cell death (due to myocyte apoptosis, inflammation, and fatty/fibrotic tissue replacement) → thinning of the right ventricular wall → dilation of the ventricle → ventricular arrhythmia and dysfunction 
- The left ventricle can also be affected, but consequences are usually less severe.
- Highly variable
- Many patients remain asymptomatic.
- Angina pectoris
- Peripheral edema, ascites, hepatic and splenic congestion
- Palpitations, syncope, possibly (particularly during or after exercise)
ARVC is diagnosed based on the AHA criteria which include the following features:
- Dysfunction and structural abnormalities of RV (can be revealed by echocardiography, MRI, or RV angiography)
- Histological characteristics (require myocardial biopsy)
- Abnormal repolarization (diagnosed with ECG)
- Depolarization/conduction abnormalities (diagnosed with ECG)
- Arrhythmias (diagnosed with ECG)
- Family history (confirmation of ARVC in a relative either by criteria, pathological examination in surgery or autopsy, or by genetic testing)
Echocardiography and cardiac MRI
- RV enlargement
- RV wall motion abnormalities
- ↓ RV EF
- Localized RV aneurysms
- Endomyocardial biopsy: fibrofatty replacement of myocardial tissue
- Genetic testing: Multiple genetic abnormalities that can cause ARVC have been identified (e.g., plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin (DSC2)). 
- Avoid intense physical exertion.
- Antiarrhythmic treatment
- Heart transplant (in severe cases that are refractory to all other treatments)
- Screening and genetic counseling for first-degree relatives 
- Definition: rare inherited cardiomyopathy which is associated with structural abnormalities of the left ventricular myocardium (prominent trabeculations and deep intertrabecular recesses)
- Clinical findings
- Diagnostics: echocardiography and/or cardiac MRI: LV wall thickening, prominent trabecular meshwork, detection of abnormal flow (within the deep intertrabecular recesses)
- Treatment: no causal treatment available
Arrhythmia-induced cardiomyopathy 
- Definition: recurring or persistent atrial or ventricular arrhythmias causing structural cardiac changes and left ventricular dysfunction (potentially reversible)
- Clinical features