Cardiomyopathies can be classified according to a variety of criteria, including the underlying genetic basis of dysfunction; indeed, some of the arrhythmia-inducing channelopathies that are included in some classifications of cardiomyopathy were alluded to earlier. For purposes of general diagnosis and therapy, however, three time-honored clinical, functional, and pathologic patterns are recognized (
Fig. 11.23
Table 11.5
Of the three major patterns, DCM is most common (90% of cases), and restrictive cardiomyopathy is the least frequent. Within each pattern, there is a spectrum of clinical severity, and in some cases clinical features overlap among the groups. In addition, each of these patterns can be caused by a specific identifiable cause, or can be idiopathic (see
Table 11.5
Dilated cardiomyopathy (DCM) is characterized by progressive cardiac dilation and contractile (systolic) dysfunction, usually with concurrent hypertrophy; regardless of the cause, the clinicopathologic patterns are similar.
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Fig. 11.23 Thethreemajorformsofcardiomyopathy.Dilatedcardiomyopathyleadsprimarilytosystolicdysfunction,whereasrestrictiveandhypertrophiccardiomyopathiesresultindiastolicdysfunction.Notethechangesinatrialand/orventriculardilationandinventricularwallthickness.Ao, Aorta;LA, leftatrium;LV, leftventricle.
Although many individuals with DCM have a familial (genetic) form, DCM can also result from various acquired myocardial insults. These include the following: • Myocarditis (an inflammatory disorder that precedes the development of cardiomyopathy in at least some cases, and is sometimes caused by viral infections)
Table 11.5 Cardiomyopathies: Functional Patterns, Causes
Toxicities, including adverse effects of chemotherapeutic agents and chronic alcoholism, a history of which can be elicited in 10% to 20% of patients
Pregnancy, so-called “peripartum cardiomyopathy”
By the time it is diagnosed, DCM has frequently already progressed to end-stage disease; the heart is dilated and poorly contractile, and at autopsy or cardiac transplant, fails to reveal any specific pathologic features. Nevertheless, genetic and epidemiologic studies suggest that at least five general pathways can lead to end-stage DCM (
Fig. 11.24
Genetic causes. DCM has a hereditary basis in 20% to 50% of cases. Over 50 genes are known to be mutated in this form of cardiomyopathy, with autosomal dominant inheritance being the predominant pattern; mutations affecting cytoskeletal proteins or proteins that link the sarcomere to the cytoskeleton (e.g., α-cardiac actin) are most commonly involved. X-linked DCM is most frequently associated with mutatons in dystrophin, a cell membrane protein that physically couples the intracellular cytoskeleton to the ECM (Chapter 22). Uncommon forms of DCM are caused by mutations of mitochondrial proteins involved in oxidative phosphorylation or fatty acid β-oxidation, presumably leading to defective ATP generation. Other genetic forms of DCM include those with mutations in cytoskeletal proteins such as desmin (the principal intermediate filament protein in cardiac myocytes), and the nuclear lamins A and C. Since contractile myocytes and conduction fibers share a common developmental pathway, congenital conduction abnormalities also can be a feature of inherited forms of DCM.