Elsevier

The Lancet

Volume 375, Issue 9716, 27 February–5 March 2010, Pages 752-762
The Lancet

Seminar
Dilated cardiomyopathy

https://doi.org/10.1016/S0140-6736(09)62023-7Get rights and content

Summary

Dilated cardiomyopathy is characterised by left ventricular dilation that is associated with systolic dysfunction. Diastolic dysfunction and impaired right ventricular function can develop. Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be exercise-induced or persistent at rest. Many patients are asymptomatic. Chronically treated patients sometimes present acutely with decompensated heart failure. Other life-threatening risks are ventricular arrhythmias and atrioventricular block, syncope, and sudden death. Genetic inheritance arises in 30–48% of patients, and inflammatory disorders such as myocarditis or toxic effects from medications, alcohol, or illicit drugs also result in dilated cardiomyopathy. Genes that cause dilated cardiomyopathy generally encode cytoskeletal and sarcomeric (contractile apparatus) proteins, although disturbance of calcium homeostasis also seems to be important. In children, disrupted mitochondrial function and metabolic abnormalities have a causal role. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress. Arrhythmia therapy and prevention of sudden death continue to be mainstays of treatment. Despite progress over the past 10 years, outcomes need to be improved.

Introduction

Cardiomyopathies are diseases of the heart muscle, characterised by abnormal findings of chamber size and wall thickness, or functional contractile abnormal findings—mainly systolic or diastolic dysfunction in the absence of coronary artery disease, hypertension, valvular disease, or congenital heart disease.1 Cardiomyopathies are classified as either primary or secondary. Primary cardiomyopathies consist of disorders solely or predominantly confined to the heart muscle, which have genetic, non-genetic, or acquired causes. Secondary cardiomyopathies are disorders that have myocardial damage as a result of systemic or multiorgan disease.2

Dilated cardiomyopathy is the most common cardiomyopathy worldwide and has many causes. In this disorder, dilation and impaired contraction of the left or both ventricles develops. It can be primary (genetic, mixed or predominantly familial non-genetic, or acquired) or secondary (eg, infiltrative or automimmune). This disease can also be diagnosed in association with recognised cardiovascular disease; however, to qualify as dilated cardiomyopathy, the extent of myocardial dysfunction cannot be explained exclusively by abnormal loading or ischaemic damage.3 Dilated cardiomyopathy is associated with sudden cardiac death and heart failure, resulting in a large cost burden because of the very high rate of hospital admission and the potential need for heart transplantation. In this Seminar, we focus on the clinical features, genetics and causative mechanisms, diagnostic strategies, treatments, outcomes, and controversies in the care of primary and secondary dilated cardiomyopathy.

Section snippets

Epidemiology and clinical features

Dilated cardiomyopathy is characterised mainly by left ventricular systolic dysfunction (abnormality of contraction), with an associated increase in mass and volume. In some cases, left ventricular diastolic abnormal findings are present. Right ventricular dilation and dysfunction can also develop but are not needed for diagnosis. Prevalence in the general population remains undefined. This disorder develops at any age, in either sex, and in people of any ethnic origin.2, 4, 5, 6 In adults,

Familial and genetic

Inherited dilated cardiomyopathy was first thought to account for a small percentage of cases only, until Michels and co-workers19 showed that about 20% of probands had family members with echocardiographic evidence of this disease when family screening was undertaken. Inherited familial dilated cardiomyopathy develops in 30–48% of cases,20 with autosomal-dominant inheritance as the predominant pattern of transmission—X-linked, autosomal recessive, and mitochondrial inheritance are less common

Infectious causes

Infectious causes of left ventricular dysfunction that are consistent with the dilated cardiomyopathy phenotype are common, including viral, bacterial, fungal, parasitic, rickettsial, and spirotricheal infections. In viral myocarditis, many viral pathogens cause the human disorder. In the past, causal diagnosis was dependent on viral culture of peripheral specimens (and rarely heart tissue) and serial serological testing. During the past 15–20 years, molecular-based testing of myocardial tissue

Toxicity-related causes

Many causes have been associated with myocardial damage and development of dilated cardiomyopathy. Long-term use of drugs such as cocaine result in heightened activation of the sympathetic nervous system, causing left ventricular dysfunction both directly and through promotion of coronary thrombosis, coronary spasm, and atherosclerosis.59 Chronic alcohol abuse is one of the most important adult causes of this disease in developed countries. Alcohol cardiomyopathy is a diagnosis of exclusion,

Peripartum cardiomyopathy

Peripartum cardiomyopathy is a disorder in which initial left-ventricular systolic dysfunction and symptoms of heart failure develop between the late stages of pregnancy and early postpartum period, typically within 1 month of predelivery and 5 months postdelivery.65 Its causes and pathogenesis are poorly understood. The disorder is common in some countries and rare in others. In most patients with this disorder, molecular markers of an inflammatory process are identified. Affected women

Mechanisms responsible for genetically defined dilated cardiomyopathy

Mechanisms associated with disease causation are force generation and transmission defects, metabolic and mechanosensory abnormalities, and disturbed calcium homeostasis.66, 67 Most genes identified so far encode either cytoskeletal or sarcomeric proteins. For cytoskeletal proteins, defects of force transmission are thought to result in the dilated cardiomyopathy phenotype, whereas defects of force generation have been speculated to cause sarcomeric protein-induced dilated cardiomyopathy.

Immune system and heart failure

Myocarditis is characterised by pathological inflammation of the myocardium, leading to chronic heart failure in a substantial number of patients younger than 40 years.80 Diagnosis for both viral and non-viral causes is based on well-established histological, immunological, and immunohistochemical criteria for endomyocardial biopsy samples. A subset of patients with myocarditis from various causes develop a chronic form of the disease that can be viral, post-infectious immune, or organ-specific

Left ventricular non-compaction

Left ventricular non-compaction has previously been regarded as a rare disease, and has been identified by various names—spongy myocardium, fetal myocardium, and non-compaction of the left ventricular myocardium.93 The abnormality is thought to represent an arrest in the normal process of myocardial compaction, the final stage of myocardial morphogenesis, resulting in persistence of many prominent ventricular trabeculations and deep intertrabecular recesses. Left ventricular non-compaction can

Treatment

Therapy of dilated cardiomyopathy is mainly directed at treatment of heart-failure symptoms and prevention of disease progression and related complications, such as end-organ dysfunction and stroke.95 Revised guideline recommendations have been published.95, 96 Diagnosis, severity of disease, and, if possible, cause of the dilated cardiomyopathy should be known so that therapy can be as precise as possible. To improve diagnosis and grading of disease severity, a new method of staging patients

Search strategy and selection criteria

We searched PubMed for reports mainly from the past 5 years, including some reports from 2000 onwards, Online Mendelian Inheritance in Man, and peer-reviewed reports on dilated cardiomyopathy. We used the search terms “dilated cardiomyopathy”, “heart failure”, “cardiomyopathy”, “DCM genetics” and “final common pathway”. No languages were excluded. We included reports that covered adult and childhood dilated cardiomyopathy from clinical and basic-science journals, and relevant reports of

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