The term “cardiomyopathy” is used to indicate myocardial dysfunction in the absence of an obstructive lesion or sustained hypertension. Cardiomyopathy can occur either in isolation or as a manifestation of a multisystem disease. Neonates who have an unrecognized cardiomyopathy may come to medical attention with a life-threatening decompensation associated with an otherwise minor illness, such as a viral upper respiratory infection. Alternatively, evidence of cardiomyopathy may be noted on an echocardiogram performed for evaluation of an unrelated problem. Other conditions cause ventricular dysfunction but may not have a long-term impact on cardiac muscle function, such as myocarditis or anomalous origin of the left coronary artery from the pulmonary artery, and will be discussed at the end of the chapter.
Mutations in multiple genes encoding proteins of the sarcomere, cytoskeleton, sarcoplasmic reticulum, nucleus, and cell membrane of the myocardial cell are now known to cause cardiomyopathy (Figure 9-1). More information regarding the structure and function of these proteins is presented in Chapter 2.
Myocyte cytoarchitecture. Various forms of cardiomyopathy may result from mutations in genes encoding multiple proteins within the cardiac myocyte. Different mutations in the same gene may cause different forms of cardiomyopathy. Abbreviations: EYA4, eyes absent homolog 4; MLP, cardiac LIM domain protein; MyBPc, myosin binding protein C; T-cap, telethonin; ZASP, muscle LIM-binding protein 3 (cypher).
Classification of cardiomyopathies is challenging and has evolved as new information has become available regarding causation. Classification based on phenotype (ventricular morphology and physiology) is practical because these characteristics are typically defined at the initial evaluation of the patient (Table 9-1). Phenotypic groups can be subdivided based on etiology (Tables 9-2, 9-3, 9-4). Unfortunately, specific causes of cardiomyopathy can present with different phenotypes in different patients or be associated with different phenotypes during the evolution of the disease in a specific patient, making classification by phenotype imperfect.
TABLE 9-1.Phenotypic Classification of Cardiomyopathy |Favorite Table|Download (.pdf) TABLE 9-1. Phenotypic Classification of Cardiomyopathy
|Arrhythmogenic right ventricular dysplasiaa |
TABLE 9-2.Conditions Associated with Phenotypic Appearance of Hypertrophic Cardiomyopathy |Favorite Table|Download (.pdf) TABLE 9-2. Conditions Associated with Phenotypic Appearance of Hypertrophic Cardiomyopathy
| ||OMIM number |
|Familial, unknown gene || |
|Myofilament (sarcomeric) mutation || |
| Thick filament || |
| β-myosin heavy chain ||160760 |
| Ventricular regulatory myosin light chain ||608758 |
| Ventricular essential myosin light chain ||608751 |
| Intermediate filament || |
| Cardiac myosin-binding protein C ||115197 |
| Thin filament || |
| Cardiac troponin T ||115195 |
| Cardiac troponin C ||613243 |
| Cardiac troponin I ||613690 |
| α-tropomyosin ||115196 |
| α-cardiac actin ||612098 |
|Z-disc mutation || |
| Cardiac LIM domain protein (cysteine- and glycine-rich ...|