Medicine

Last updated on: August 14th, 2020

Dilated cardiomyopathy

Clinicals - History

Symptoms of heart failure

These are encountered in 80% of patients. Heart failure is a consequence of the progressive left ventricular (LV) dilation and systolic dysfunction encountered in dilated cardiomyopathy (DCM).

Palpitations

This is due to supraventricular or ventricular tachyarrhythmias. DCM predisposes to arrhythmias due to the disruption of the conduction system of the heart caused by progressive dilation, and progressive interstitial fibrosis contributing to an arrhythmic substrate. In individuals with DCM caused by inflammatory or infiltrative disease, the resulting injury to the myocardium may also be a contributing factor.

Constitutional symptoms

These are prominent in advanced cases, and include anorexia, nausea, abdominal discomfort, and cachexia. They are a consequence of chronic heart failure.

Sudden cardiac death

Sudden cardiac death may occur following ventricular arrhythmias such as monomorphic or polymorphic ventricular tachycardia, or ventricular fibrillation. The pathophysiology underlying the occurrence of arrhythmias is discussed under "palpitations".

Positive family history

Familial transmission occurs in 20% to 35% of cases. Autosomal dominant inheritance is the most common form of transmission. However, autosomal recessive, x-linked, and mitochondrial inheritance may also occur.

Chronic alcohol abuse

Chronic alcohol abuse accounts for 21% to 36% of cases in high-income countries. In this context, the alcohol intake must have been >80-100 g/day for >10 years. Alcohol appears to exert a direct toxic effect on the myocardium, while also depressing cardiac contractility and activating the neurohormonal system. All of these factors contribute to the development of DCM.

Recreational drug use

Cocaine and methamphetamine abuse is an important cause of DCM in younger adults. These drugs are potent sympathomimetic agents. They appear to cause cardiac toxicity via myocardial ischemia due to increased oxygen consumption, prothrombotic effects, coronary vasospasm, and accelerated coronary atherosclerosis.

Pregnancy

DCM may occur in the last month of pregnancy or within the first five (5) months of delivery, without any discernible cause. This is termed "peripartum cardiomyopathy". The underlying pathophysiology is still unclear.

Chemotherapy

DCM is an important complication of anthracycline (e.g. doxorubicin, daunorubicin, etc.) therapy. This may occur during the therapy, or any time afterwards. The causes of anthracycline-induced cardiotoxicity appear to include oxidative stress, changes in mitochondrial membrane permeability, and suppression of respiratory chain activity.

HIV Infection

Human immunodeficiency virus (HIV) infection can also give rise to DCM, and should be considered in individuals whose DCM has no clear cause. The underlying pathogenic mechanisms include: direct myocyte toxicity, activation of indirect pathways that induce myocardial inflammation and damage, and cardiac autoimmunity.


Micronutrient deficiency is common in HIV-infected persons due to gut malabsorption, diarrhea, and wasting syndrome. The resulting free radical formation may cause further myocardial injury. Therapy with the reverse-transcriptase inhibitor zidovudine (AZT) may cause myocardial damage. AZT may potentially contribute to the above, or independently cause DCM.

Autoimmune disease

Certain autoimmune conditions are known to cause DCM. These include: systemic lupus erythematosus, connective tissue diseases (such as scleroderma and dermatomyositis), and vasculitides (e.g., eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa, and Kawasaki disease). The underlying mechanisms of these conditions include immune-mediated cardiac injury and thrombotic or inflammatory microvascular coronary disease.

Chagas disease

In endemic regions, Chagas disease (caused by infection with the protozoan parasite Trypanosoma cruzi) is an important etiology of DCM. The pathogenesis is incompletely understood but may involve several mechanisms, including: parasite-dependent myocardial damage, immune-mediated myocardial injury, and microvascular and neurogenic disturbances.

Clinicals - Examination

Signs of heart failure

These include tachycardia, peripheral edema, an elevated jugular venous pressure, bibasal pulmonary crackles (due to pulmonary edema), and a gallop rhythm. Heart failure is a consequence of the progressive left ventricular (LV) dilation and systolic dysfunction encountered in dilated cardiomyopathy (DCM).

Apical deviation

The apex beat is typically deviated inferolaterally. This is a consequence of the dilation of the left ventricle.

Signs of mitral regurgitation

The holosystolic murmur of mitral regurgitation may be present. This is functional in nature, and caused by mitral annular dilatation.

Differential Diagnoses

Ischemic cardiomyopathy

This is phenotypically similar to dilated cardiomyopathy (DCM), and may at times be almost impossible to tell apart clinically. Features suggestive of this diagnosis include the presence of clinical risk factors or symptoms suggestive of ischemic heart disease (IHD); and segmental wall motion abnormalities on echocardiography. 


Coronary angiography can establish the diagnosis by demonstrating ≥50% stenosis of the left main stem, proximal left anterior descending artery, or two or more epicardial coronary arteries. Late gadolinium enhancement (LGE)-cardiovascular magnetic resonance (CMR) is an alternative. In individuals with ischemic cardiomyopathy, this will show evidence of prior myocardial infarction.

Cirrhotic cardiomyopathy

This is an important yet often under-recognized complication of cirrhosis.


Features suggestive of this diagnosis include the presence of advanced chronic liver cell disease, QT prolongation on the ECG, and a normal left ventricular ejection fraction (LVEF) on rest with latent systolic dysfunction that is unmasked by physiological, pharmacological, or iatrogenic stress.

Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease of the cardiac muscle that predominantly affects the right ventricle, and is characterized by progressive loss of right ventricular myocardium, with replacement by fibrofatty tissue.


This condition can be differentiated from DCM by the presence of right ventricular (RV) regional wall motion abnormalities or localized dyssynchrony in the subtricuspid region upon echocardiography, along with RV remodeling and dysfunction.


LGE-CMR may also show characteristic patterns, including LGE in the RV free wall and/or left ventricular (LV) inferolateral subepicardium, or circumferential LGE in the LV midwall extending to the right side of septum.

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. It is characterised by abnormal thickening of the ventricular walls in the absence of abnormal loading conditions. Advanced HCM may be phenotypically similar to DCM.


Advanced HCM can be differentiated from DCM by the presence of a longstanding history of HCM; increased LV wall thickness, asymmetric septal thickening, and systolic anterior motion of the anterior leaflet of the mitral valve on echocardiography; and extensive patchy myocardial fibrosis on LGE-CMR.

Hypertensive heart disease

Hypertensive heart disease can be distinguished from DCM by the presence of a history of chronic, poorly controlled hypertension, and increased LV wall thickness upon echocardiography.

Athlete's heart

Physiological LV dilation has been reported in up to 15% of highly trained athletes. Among athletes participating in extreme endurance sports this be associated with a concomitant reduction in resting LVEF, potentially resulting in misdiagnosis as DCM.


Athlete's heart can be distinguished from DCM by the absence of signs and symptoms of heart failure; presence of a normal ECG; normal LV diastolic function, LV peak systolic strain, and a supranormal contractile reserve on echocardiography; and, a high peak VO2 on cardiopulmonary exercise testing.

Investigations - Diagnosis

Echocardiography

Echocardiography will typically show global left ventricular hypokinesis, although regional wall motion abnormalities may also exist. Importantly, left ventricular and atrial dilatation may be mild in early disease. Functional mitral regurgitation due to annular dilatation may also be noted. Right ventricular involvement is variable.

Cardiac MRI

This accurately assesses ventricular volumes, wall thickness, and contractile function, thus helping confirm the diagnosis of dilated cardiomyopathy (DCM). Cardiac MRI is also capable of detecting myocardial necrosis or scarring.

ECG

ECGs usually show no findings or nonspecific findings. These include prolongation of the PR interval, poor R wave progression or pathological Q waves in the lateral chest leads, and electrocardiographic evidence of left ventricular hypertrophy. atrioventricular block, left bundle branch block, and left anterior hemiblock may also be seen.

Chest radiographs

These may reveal cardiomegaly and pulmonary venous redistribution. Radiographic evidence of pulmonary edema may also be seen.

Investigations - Management

Endomyocardial biopsy

Endomyocardial biopsy is indicated if a specific diagnosis that would influence therapy is suspected. Typical histological findings include irregular myocyte hypertrophy, with or without areas of fibrosis and myocyte damage. The presence of a lymphocytic infiltrate indicates infectious or immune-mediated inflammation. Histologic features of sarcoidosis, hemochromatosis, or specific metabolic and storage disorders may be present. PCR analysis may help identify viral genome within the myocardium.

Genetic studies

Genetic testing is now commercially available for dilated cardiomyopathy (DCM). This consists of a cardiomyopathy panel of 20 to 50 genes. This is also helpful to identify at-risk family members.

Cardiac biomarkers

B-type natriuretic peptide (BNP) and N-terminal-BNP levels are elevated in proportion to the severity of heart failure. This is used in assessing the risk of death, and the need for future cardiac transplantation.

Management - Supportive

Treatment of heart failure

Heart failure is a major clinical manifestation of dilated cardiomyopathy (DCM). Treatment should follow the standard guidelines on the management of heart failure.

Prevention of thromboembolism

These patients are at risk of thromboembolism, particularly if there is intermittent or sustained atrial fi brillation or flutter. In such instances, thromboembolic prophylaxis should be considered.

Implantable cardioverter-defibrillator (ICD) implantation

ICD implantation is recommended in patients with DCM who have symptomatic HF and an LVEF ≤35% even after at least 3 months of optimal medical therapy; and provided they are expected to survive substantially longer than one year with good functional status. 

Multidisciplinary care

There is evidence that enrolment of patients with DCM in a multidisciplinary heart failure service, results in reduced hospital admissions and mortality.

Patient education

Patient and caregiver education is very important. This includes information about: dietary and lifestyle measures, self-monitoring strategies, medication adherence, and avoidance of potentially harmful drugs.

Exercise training

Exercise training has been shown to improve quality of life. However, it appears to have little effect on overall survival.

Salt and fluid restriction

Salt and fluid restriction is commonly practiced. However, there is little evidence to support this intervention.

Management - Specific

Cardiac transplantation

Cardiac transplantation is the only curative measure, and should be considered in persons with intractable advanced symptomatic heart failure despite optimal medical and device therapy.

Mechanical circulatory support devices

Long-term left-sided ventricular or biventricular assist devices can be used as a bridge to cardiac transplantation.

Other surgical approaches

Other surgical approaches attempting in persons with dilated cardiomyopathy (DCM) include: surgical correction of mitral regurgitation, left ventricular remodelling, and the use of restraints to prevent progressive ventricular dilatation. However, none of these methods has been shown to improve survival.

Sodium channel inhibitors

Patients with gain-of-function mutations of the SCN5A gene may have their phenotype reversed by drugs that inhibit the sodium channel, such as amiodarone or flecainide.

Immunosuppression

In patients with lymphocytic myocarditis (i.e. indicating infectious or immune-mediated infiltration) immunosuppressive therapy has been attempted, either as prednisolone alone, or in combination with azathioprine or ciclosporin. However, most trials show no survival or functional benefit.


However, persons with circulating cardiac autoantibodies and no detectable viral genome in the myocardium, and patients with HLA upregulation on endomyocardial biopsy appear to represent a subgroup with a more favourable response to immunosuppressive therapy.

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References

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