Cardiomyopathies (CMPs) are a group of diseases with multiple etiologies and heterogeneous phenotypes, ranging from microscopic changes in cardiomyocytes in asymptomatic patients to cases of fulminant heart failure with fluid retention, and perfusion and heart rhythm changes. A CMP was initially defined as a heart muscle disease caused by genetic defects, myocyte injury or myocardial infiltration, and characterized by structural and functional abnormalities in the absence of congenital disease, valvular disease or hypertension.
The classification of CMP is used to standardize the nomenclature, by grouping disorders that share morphological characteristics or biochemical and genetic abnormalities.
In 1957, Brigden was the first author to use the term CMP to describe patients with idiopathic (noncoronary) CMP, many of them with familial disease.
In 1980, with the publication of the report of the World Health Organization (WHO)/International Society and Federation of Cardiology (ISFC),
In 1996, a new WHO/ISFC classification was proposed.
In 1990, β-myosin heavy chain gene mutation was reported in patients with hypertrophic CMP and in dilated CMP years later.
In the classification of CMPs offered by the American Heart Association in 2006, the diseases were defined as “a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction, which usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation, due to a variety of etiologies that frequently are genetic. CMPs are either confined to the heart or are part of generalized systemic disorders”. Within this definition, CMPs are associated with failed cardiac function, that may be either mechanical (diastolic or systolic), or a primary electrical disease. Also, ion channelopathies are defined as distinct entities (long QT syndrome and Brugada syndrome), as primary electrical diseases, without histological abnormalities, responsible for the arrhythmic substrate.
This classification tries to cover new methods of diagnostic molecular biology, for the characterization of genetic mutations and, at cellular level, of protein expression. The American classification divides CMPs into two large groups: primary CMPs, comprising those confined to heart muscle (subdivide into genetic, mixed, and acquired);
The 2008 European statement (
Therefore, despite differences between current American and European recommendations, both classify cardiac muscle diseases based on their morphological and functional changes.3,4 The identification of genetic determinants in the etiology of CMPs allowed their sub-classification into familial and non-familial forms in the European position statement, while in the American classification the categories are “genetic”, “mixed” and “acquired”.
A genome-based classification is still structurally complex, since some gene mutations affecting the sarcomere may lead to different phenotypes, such as dilated CMP and hypertrophic CMP. Troponin I mutation can lead to anatomical changes similar to those seen in the restrictive and hypertrophic forms, and desmosomal gene mutations are associated with arrhythmogenic right ventricular dysplasia, but can also lead to dilated CMP phenotype, making classification difficult. For this reason, a classification based on morphological, clinical, and genetic features is important.
A descriptive nosological classification encompassing these individual attributes and allowing a common platform for collaborative research efforts was published in 2013.
One of the advantages of this new classification lies in the inclusion of individuals at early stages of the disease that do not show clear phenotypic alterations. In family members with known mutation but still no disease manifestation, the preclinical diagnosis can be made by the genetic study. This classification could also be useful for sports recommendations in cases that are in the “gray area” to receive a definitive recommendation.
However, the MOGE(S) classification system does not include some MCP groups, such as tachycardia-induced CMP, endocrine CMPs and paripartum CMP. Finally, the complexity of the MOGE(S) system could hamper its use in clinical practice. Besides, key information, such as the molecular genetic diagnosis, is only available in a few centers and countries in the world. The authors of the MOGE nomenclature have also developed an application, accessible at
Since most CMPs have a familial origin, genetic testing has been crucial in the clinical context as several new genes and mutations have been detected in the different etiologies of CMPs. Several genetic diseases have been identified; the penetrance of the genetic mutation is variable, and phenotypic manifestations are age dependent. Most genetic CMPs are autosomal dominant traits, with a minority of autosomal recessive, X-linked recessive or dominant (rare).
Recently, the role of the atrium in cardiac dynamics and in systemic and pulmonary circulation has been highlighted, and the concept of atrial CMP has emerged. Atrial CMP would be defined as structural, architectural, contractile, or electrophysiological changes that may produce relevant clinical manifestations.