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Definition, classification, and staging of the adult cardiomyopathies: A proposal for revision
Journal of Cardiac Failure Vol. 10 No. 1 2004
Perspective*
Definition, Classification, and Staging of the Adult Cardiomyopathies: A Proposal for Revision THOMAS D. GILES, MD,1 KANU CHATTERJEE, MB,2 JAY N. COHN, MD,3 WILSON S. COLUCCI, MD,4 ARTHUR M. FELDMAN, MD, PhD,5 VICTOR J. FERRANS,† MD, PhD,6 AND ROBERT ROBERTS, MD7 New Orleans, Louisiana; San Francisco, California; Minneapolis, Minnesota; Boston, Massachussets; Philadelphia, Pennsylvania; Bethesda, Maryland; Houston, Texas
Clinicians have had reason to find the classification of cardiomyopathies confusing. Classification of cardiomyopathies has focused on recognition of clinical phenotypes, often associated with heart failure, thus leaving the clinician uncertain as to how to deal with early, asymptomatic disease. This latter situation is unfortunate because therapeutic intervention at an early stage may halt the progression of many cardiomyopathies and prevent the development of heart failure. In 2000, we began to meet as an interested group to undertake a reclassification of the cardiomyopathies, building on previous classifications and recognizing new information from both basic and applied research. Previous classifications of the cardiomyopathies have contributed to research into the pathophysiology of myocardial diseases and provided a basis for clinical diagnosis and patient management. Goodwin, in 1964, first proposed a clinicopathologic classification of cardiomyopathy that was useful in differential diagnosis1; he subsequently modified his classification in 1972.2 Diagnostic categories included dilated (congestive, fibrotic), hypertrophic, and restrictive. In many, if not most, instances, the clinical recognition of cardiomyopathy occurred when the clinical syndrome of heart failure was present. In fact, the term was often used when
dealing with patients who had heart failure of uncertain etiology. It is not surprising that idiopathic cardiomyopathy was considered a “disease” and often equated with heart failure. The World Health Organization’s (WHO) first proposal to classify the cardiomyopathies was published in 1968 and suggested that the term “idiopathic cardiomegaly” be substituted for cardiomyopathy.3 In 1980, WHO, working with the International Society and Federation of Cardiology (ISFC), developed a new classification that recommended that cardiomyopathies be divided into “cardiomyopathy,” in which the causes were unknown, and “specific heart muscle diseases,” in which a definite etiology could be identified.4 However, this classification relegated the entire concept of cardiomyopathy to heart muscle disease of unknown cause rather than simply defining such cardiomyopathies as being of unknown etiology or idiopathic. The latest classification by the WHO/ISFC was published in 1996 and recommended that cardiomyopathies be “defined as diseases of the myocardium associated with cardiac dysfunction” and that they be classified by the dominant pathophysiology, or, if possible, by etiologic/pathogenetic factors.”5 Thus, cardiomyopathies would be pathophysiologically classified as dilated, hypertrophic, restrictive, and arrthymogenic right-ventricular cardiomyopathies. The term “specific cardiomyopathies” is now used to describe heart muscle diseases that are associated with specific cardiac or systemic disorders. Both basic and applied research findings have now contributed to an increased understanding of the various phenotypic expressions of cardiomyopathy. It is now apparent that cardiomyopathy may have many causes resulting from genetic and environmental interactions (Fig. 1). In addition, polymorphisms in genes encoding a variety of cardiovascular proteins may alter the response of an individual to either pharmacologic or nonpharmacologic therapy, thus affecting the phenotype. Moreover, a single etiologic factor (eg, hypertension) may result in differing phenotypes based on the specific genotype of an individual. Clinically recognizable heart failure results from a progression of cardiomyopathy (ie, heart failure) is an advanced
*Perspectives reflect the views of the author(s) and are not necessarily the views of the Editors of the Journal of Cardiac Failure or the Heart Failure Society of America. From the 1Louisiana State University Health Services Center, New Orleans, Louisiana, USA; 2University of California at San Francisco, San Francisco, California; 3University of Minnesota, Minneapolis, Minnesota; 4 Boston University Medical Center, Boston, Massachusetts; 5Jefferson Medical College of Jefferson University, Philadelphia, Pennsylvania; 6National Heart, Blood, and Lung Institute, Bethesda, Maryland; 7Baylor College of Medicine, Houston, Texas. † Deceased Manuscript received March 24, 2003; revised manuscript received July 7, 2003; revised manuscript accepted July 11, 2003. Reprint requests: Thomas D. Giles, MD, LSUHSC, Cardiovascular Research, Room 331 East, 1542 Tulane Avenue, Box T3M-3, New Orleans, LA 70112. 1071-9164/$ - see front matter 쑕 2004 Elsevier Inc. All rights reserved. doi:10.1016/S1071-9164(03)00580-3
6
Definition, Classification, and Staging of the Adult Cardiomyopathies
•
Giles et al
7
Fig. 1. The basis for the classification of cardiomyopathies is presented. Genotypic and environmental factors produce various pathophysiologic alterations in the myocardium resulting in recognizable phenotypes. Ventricular wall tension plays a great role in cardiac remodeling and is calculated according to the formula, T ⫽ P · r/2h (T ⫽ ventricular wall tension; P ⫽ intraventricular pressure; r ⫽ ventricular radius; h ⫽ ventricular wall thickness). See text for an explanation of the various stages of presentation of the cardiomyopathies.
stage (phenotype) representing decompensated cardiomyopathy. Cardiomyopathy may be present for many years before the appearance of clinically detectable disease, much less overt heart failure. Also, heart failure is but 1 possible clinical outcome of cardiomyopathy. For example, cardiac dysrhythmias and sudden death may be clinical representations of cardiomyopathy. In this first report, we provide a new staging and classification system of the cardiomyopathies (Tables 1 and 2). Recognizing that there is a continuum between the initiation of heart muscle disease and the appearance of clinical heart failure, arrhythmias and sudden death, we have introduced the concept of staging of cardiomyopathies. Staging of the cardiomyopathies will serve to couple diagnosis with pathophysiology and reduce confusion of the diagnosis of cardiomyopathy with the clinical entities of heart failure, arrhythmias, and sudden death. The classification of cardiomyopathy is intended to be of value to clinicians, scientists/investigators, governments, health care planners, third-party payers, and, most importantly, patients. The classification builds on previous systems and contains 2 notable advances: recognition of early stages of cardiomyopathy, before the onset of clinical heart failure, and an emphasis on precise determination of etiology. Further, in regard to etiology, this classification, unlike previous ones, contains a “genetic” category and the term “idiopathic” is no longer used as a specific disease classification. It is perhaps in the field of genetics in which the most rapid expansion of knowledge is occurring, with genetic abnormalities represented by all of the phenotypic expressions recognized by clinicians. Transgenic animals of cardiomyopathy
have provided much insight by demonstrating the phenotypic variations possible resulting from the same genetic abnormality.
Table 1. Stages of Cardiomyopathy Stage 1 (latent or potential): This stage of cardiomyopathy is present when a factor known to be associated with cardiomyopathy is present (eg, genetic abnormality, diabetes mellitus), but no evidence of heart muscle disease can be detected even with sensitive noninvasive techniques. Stage 2 (early or subclinical): This stage of cardiomyopathy is present when there is evidence of heart muscle disease but no symptoms are present and cardiac remodeling may, or may not, be present (eg, postmyocardial infarction with a slightly reduced left ventricular ejection fraction diabetes mellitus with evidence of diastolic dysfunction by echocardiography). Stage 3 (late or advanced): This stage of cardiomyopathy is present when evidence of heart muscle disease and symptoms are present. Cardiac remodeling results in dilated or nondilated forms. Nondilated cardiomyopathies may be hypertrophic or only associated with restrictive physiology. These descriptive terms represent differing phenotypes that may or may not be characteristic of certain etiologies or pathophysiologic mechanisms, but may be helpful to the clinician in differential diagnosis. In Stage 3, the clinical state of heart failure is characterized by: 1) abnormal relationship between ventricular filling pressure and output; 2) abnormal cardiovascular autonomic function; 3) activation of neurohormonal systems; and 4) symptoms of dyspnea, fatigue, edema, and cardiac rhythm disturbances. The clinical evaluation of a patient with cardiomyopathy, regardless of stage, is not complete until an attempt has been made to identify etiology and pathophysiology.
8 Journal of Cardiac Failure Vol. 10 No. 1 Februrary 2004 Table 2. Etiological Classification Genetic Familial (autosomal dominant, autosomal recessive, x-linked, mitochondrial). Sporadic Ischemic (coronary atherosclerosis or vasculitis, anomalous coronary artery origin) Infectious (viral, bacterial, rikettsial, protozoal) Hyperergopathic (“overwork”) Valvular heart disease Hypertension Toxic Alcohol Cocaine Antineoplastic drugs Heavy metals Cardiomyopathy not otherwise specified (NOS) Metabolic Endocrine (diabetes mellitus, thyroid disorders, parathyroid disorders, acromegaly, pheochromocytoma, carcinoid) Electrolyte disturbances Nutritional (thiamine, selenium, carnitine deficiency, etc.) Neoplastic diseases Immunocytic dyscrasias (eg, amyloidosis) Collagen vascular disease Systemic lupus erythematosus, progressive systemic sclerosis, Churg-Strauss, mixed connective tissue disease Physical agents Ionizing radiation Electric shock Trauma Associated with pregnancy* Immunologically mediated Transplant rejection Postvaccinal *These categories may eventually be assigned to other existing categories after a more precise delineation of pathophysiology.
The following classification and staging should be recognized as a “work in progress” that will evolve as more is learned about the pathophysiology of cardiomyopathy. The next task will be to develop criteria for the diagnosis of specific categories of cardiomyopathy. Classification of the Cardiomyopathies Cardiomyopathy is defined as disease of the myocardium (the myocardium is composed of myocytes, extracellular matrix proteins, the microcirculation, cardiac conducting system, and other formed elements). The overall basis for the classification scheme is presented in Fig. 1. Cardiomyopathies are classified according to: (1) stage at presentation, and (2) etiologic group (cardiomyopathy of multiple causes will be designated as pluricausal); if an etiologic or pathophysiologic mechanism cannot be identified, the cardiomyopathy will be termed as unidentified etiology or not otherwise specified. References 1. Goodwin JF. Cardiac function in primary myocardial disorders. BMJ 1964;1:1527–33. 2. Goodwin JF. Classification of cardiomyopathies. Mod Concepts Cardiovasc Dis 1972;41:41–66. 3. Fejfar Z. Idiopathic cardiomegaly, accounts of international meetings. Bull WHO 1968;38:979–92. 4. Report of the WHO/ISFC Task Force on the definition and classification of cardiomyopathies. Br Heart J 1980;44:672–3. 5. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996;93:841–2.
Perspective*
Definition, Classification, and Staging of the Adult Cardiomyopathies: A Proposal for Revision THOMAS D. GILES, MD,1 KANU CHATTERJEE, MB,2 JAY N. COHN, MD,3 WILSON S. COLUCCI, MD,4 ARTHUR M. FELDMAN, MD, PhD,5 VICTOR J. FERRANS,† MD, PhD,6 AND ROBERT ROBERTS, MD7 New Orleans, Louisiana; San Francisco, California; Minneapolis, Minnesota; Boston, Massachussets; Philadelphia, Pennsylvania; Bethesda, Maryland; Houston, Texas
Clinicians have had reason to find the classification of cardiomyopathies confusing. Classification of cardiomyopathies has focused on recognition of clinical phenotypes, often associated with heart failure, thus leaving the clinician uncertain as to how to deal with early, asymptomatic disease. This latter situation is unfortunate because therapeutic intervention at an early stage may halt the progression of many cardiomyopathies and prevent the development of heart failure. In 2000, we began to meet as an interested group to undertake a reclassification of the cardiomyopathies, building on previous classifications and recognizing new information from both basic and applied research. Previous classifications of the cardiomyopathies have contributed to research into the pathophysiology of myocardial diseases and provided a basis for clinical diagnosis and patient management. Goodwin, in 1964, first proposed a clinicopathologic classification of cardiomyopathy that was useful in differential diagnosis1; he subsequently modified his classification in 1972.2 Diagnostic categories included dilated (congestive, fibrotic), hypertrophic, and restrictive. In many, if not most, instances, the clinical recognition of cardiomyopathy occurred when the clinical syndrome of heart failure was present. In fact, the term was often used when
dealing with patients who had heart failure of uncertain etiology. It is not surprising that idiopathic cardiomyopathy was considered a “disease” and often equated with heart failure. The World Health Organization’s (WHO) first proposal to classify the cardiomyopathies was published in 1968 and suggested that the term “idiopathic cardiomegaly” be substituted for cardiomyopathy.3 In 1980, WHO, working with the International Society and Federation of Cardiology (ISFC), developed a new classification that recommended that cardiomyopathies be divided into “cardiomyopathy,” in which the causes were unknown, and “specific heart muscle diseases,” in which a definite etiology could be identified.4 However, this classification relegated the entire concept of cardiomyopathy to heart muscle disease of unknown cause rather than simply defining such cardiomyopathies as being of unknown etiology or idiopathic. The latest classification by the WHO/ISFC was published in 1996 and recommended that cardiomyopathies be “defined as diseases of the myocardium associated with cardiac dysfunction” and that they be classified by the dominant pathophysiology, or, if possible, by etiologic/pathogenetic factors.”5 Thus, cardiomyopathies would be pathophysiologically classified as dilated, hypertrophic, restrictive, and arrthymogenic right-ventricular cardiomyopathies. The term “specific cardiomyopathies” is now used to describe heart muscle diseases that are associated with specific cardiac or systemic disorders. Both basic and applied research findings have now contributed to an increased understanding of the various phenotypic expressions of cardiomyopathy. It is now apparent that cardiomyopathy may have many causes resulting from genetic and environmental interactions (Fig. 1). In addition, polymorphisms in genes encoding a variety of cardiovascular proteins may alter the response of an individual to either pharmacologic or nonpharmacologic therapy, thus affecting the phenotype. Moreover, a single etiologic factor (eg, hypertension) may result in differing phenotypes based on the specific genotype of an individual. Clinically recognizable heart failure results from a progression of cardiomyopathy (ie, heart failure) is an advanced
*Perspectives reflect the views of the author(s) and are not necessarily the views of the Editors of the Journal of Cardiac Failure or the Heart Failure Society of America. From the 1Louisiana State University Health Services Center, New Orleans, Louisiana, USA; 2University of California at San Francisco, San Francisco, California; 3University of Minnesota, Minneapolis, Minnesota; 4 Boston University Medical Center, Boston, Massachusetts; 5Jefferson Medical College of Jefferson University, Philadelphia, Pennsylvania; 6National Heart, Blood, and Lung Institute, Bethesda, Maryland; 7Baylor College of Medicine, Houston, Texas. † Deceased Manuscript received March 24, 2003; revised manuscript received July 7, 2003; revised manuscript accepted July 11, 2003. Reprint requests: Thomas D. Giles, MD, LSUHSC, Cardiovascular Research, Room 331 East, 1542 Tulane Avenue, Box T3M-3, New Orleans, LA 70112. 1071-9164/$ - see front matter 쑕 2004 Elsevier Inc. All rights reserved. doi:10.1016/S1071-9164(03)00580-3
6
Definition, Classification, and Staging of the Adult Cardiomyopathies
•
Giles et al
7
Fig. 1. The basis for the classification of cardiomyopathies is presented. Genotypic and environmental factors produce various pathophysiologic alterations in the myocardium resulting in recognizable phenotypes. Ventricular wall tension plays a great role in cardiac remodeling and is calculated according to the formula, T ⫽ P · r/2h (T ⫽ ventricular wall tension; P ⫽ intraventricular pressure; r ⫽ ventricular radius; h ⫽ ventricular wall thickness). See text for an explanation of the various stages of presentation of the cardiomyopathies.
stage (phenotype) representing decompensated cardiomyopathy. Cardiomyopathy may be present for many years before the appearance of clinically detectable disease, much less overt heart failure. Also, heart failure is but 1 possible clinical outcome of cardiomyopathy. For example, cardiac dysrhythmias and sudden death may be clinical representations of cardiomyopathy. In this first report, we provide a new staging and classification system of the cardiomyopathies (Tables 1 and 2). Recognizing that there is a continuum between the initiation of heart muscle disease and the appearance of clinical heart failure, arrhythmias and sudden death, we have introduced the concept of staging of cardiomyopathies. Staging of the cardiomyopathies will serve to couple diagnosis with pathophysiology and reduce confusion of the diagnosis of cardiomyopathy with the clinical entities of heart failure, arrhythmias, and sudden death. The classification of cardiomyopathy is intended to be of value to clinicians, scientists/investigators, governments, health care planners, third-party payers, and, most importantly, patients. The classification builds on previous systems and contains 2 notable advances: recognition of early stages of cardiomyopathy, before the onset of clinical heart failure, and an emphasis on precise determination of etiology. Further, in regard to etiology, this classification, unlike previous ones, contains a “genetic” category and the term “idiopathic” is no longer used as a specific disease classification. It is perhaps in the field of genetics in which the most rapid expansion of knowledge is occurring, with genetic abnormalities represented by all of the phenotypic expressions recognized by clinicians. Transgenic animals of cardiomyopathy
have provided much insight by demonstrating the phenotypic variations possible resulting from the same genetic abnormality.
Table 1. Stages of Cardiomyopathy Stage 1 (latent or potential): This stage of cardiomyopathy is present when a factor known to be associated with cardiomyopathy is present (eg, genetic abnormality, diabetes mellitus), but no evidence of heart muscle disease can be detected even with sensitive noninvasive techniques. Stage 2 (early or subclinical): This stage of cardiomyopathy is present when there is evidence of heart muscle disease but no symptoms are present and cardiac remodeling may, or may not, be present (eg, postmyocardial infarction with a slightly reduced left ventricular ejection fraction diabetes mellitus with evidence of diastolic dysfunction by echocardiography). Stage 3 (late or advanced): This stage of cardiomyopathy is present when evidence of heart muscle disease and symptoms are present. Cardiac remodeling results in dilated or nondilated forms. Nondilated cardiomyopathies may be hypertrophic or only associated with restrictive physiology. These descriptive terms represent differing phenotypes that may or may not be characteristic of certain etiologies or pathophysiologic mechanisms, but may be helpful to the clinician in differential diagnosis. In Stage 3, the clinical state of heart failure is characterized by: 1) abnormal relationship between ventricular filling pressure and output; 2) abnormal cardiovascular autonomic function; 3) activation of neurohormonal systems; and 4) symptoms of dyspnea, fatigue, edema, and cardiac rhythm disturbances. The clinical evaluation of a patient with cardiomyopathy, regardless of stage, is not complete until an attempt has been made to identify etiology and pathophysiology.
8 Journal of Cardiac Failure Vol. 10 No. 1 Februrary 2004 Table 2. Etiological Classification Genetic Familial (autosomal dominant, autosomal recessive, x-linked, mitochondrial). Sporadic Ischemic (coronary atherosclerosis or vasculitis, anomalous coronary artery origin) Infectious (viral, bacterial, rikettsial, protozoal) Hyperergopathic (“overwork”) Valvular heart disease Hypertension Toxic Alcohol Cocaine Antineoplastic drugs Heavy metals Cardiomyopathy not otherwise specified (NOS) Metabolic Endocrine (diabetes mellitus, thyroid disorders, parathyroid disorders, acromegaly, pheochromocytoma, carcinoid) Electrolyte disturbances Nutritional (thiamine, selenium, carnitine deficiency, etc.) Neoplastic diseases Immunocytic dyscrasias (eg, amyloidosis) Collagen vascular disease Systemic lupus erythematosus, progressive systemic sclerosis, Churg-Strauss, mixed connective tissue disease Physical agents Ionizing radiation Electric shock Trauma Associated with pregnancy* Immunologically mediated Transplant rejection Postvaccinal *These categories may eventually be assigned to other existing categories after a more precise delineation of pathophysiology.
The following classification and staging should be recognized as a “work in progress” that will evolve as more is learned about the pathophysiology of cardiomyopathy. The next task will be to develop criteria for the diagnosis of specific categories of cardiomyopathy. Classification of the Cardiomyopathies Cardiomyopathy is defined as disease of the myocardium (the myocardium is composed of myocytes, extracellular matrix proteins, the microcirculation, cardiac conducting system, and other formed elements). The overall basis for the classification scheme is presented in Fig. 1. Cardiomyopathies are classified according to: (1) stage at presentation, and (2) etiologic group (cardiomyopathy of multiple causes will be designated as pluricausal); if an etiologic or pathophysiologic mechanism cannot be identified, the cardiomyopathy will be termed as unidentified etiology or not otherwise specified. References 1. Goodwin JF. Cardiac function in primary myocardial disorders. BMJ 1964;1:1527–33. 2. Goodwin JF. Classification of cardiomyopathies. Mod Concepts Cardiovasc Dis 1972;41:41–66. 3. Fejfar Z. Idiopathic cardiomegaly, accounts of international meetings. Bull WHO 1968;38:979–92. 4. Report of the WHO/ISFC Task Force on the definition and classification of cardiomyopathies. Br Heart J 1980;44:672–3. 5. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996;93:841–2.