Background

Cardiomyopathies have received attention in the news with well publicized deaths of prominent young athletes. Cardiomyopathies are a class of heart disease, classically divided into restrictive, hypertrophic, and dilated. Most cases are idiopathic, that is, the cause is not known or incompletely understood. In addition, there are a number of medical diseases including amyloidosis and alcoholism which may lead to clinical conditions mimicking these categories of cardiomyopathies. Medical therapy can be used but many patients may benefit from a heart transplantation.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Amyloidosis
Hemochromatosis
Cardiomyopathy in AIDS: a pathophysiological perspective. Lewis W. Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.	Prog Cardiovasc Dis 2000 Sep-Oct;43(2):151-70 Abstract quote This report addresses issues of pathogenesis, pathophysiology, and epidemiology of an increasingly prevalent cardiomyopathy in acquired immunodeficiency syndrome (AIDS). As patient survival increases with more effective antiretroviral therapy, cardiomyopathy in AIDS will become more apparent. The interactions of cellular and organism factors in AIDS and their relationships to the development of cardiomyopathy are reviewed herein. Amongst the factors addressed in this review are: (1) comorbid conditions found with AIDS, (2) the role of inflammatory heart disease and cytokines in the development of AIDS cardiomyopathy, (3) the pathogenetic role of vascular cells and myocardial cells in the development of cardiomyopathy, (4) the role of myocardial retroviral infection in AIDS, and (5) the impact of toxicity from antiretroviral therapy on the development of cardiomyopathy. Because it is possible that more than 1 of these factors is present in a given patient inflicted with AIDS, a multifactorial pathogenesis in AIDS cardiomyopathy must be considered.
Alcohol abuse and dilated cardiomyopathy in men. Gavazzi A, De Maria R, Parolini M, Porcu M. Divisione di Cardiologia, IRCCS Policlinico San Matteo, Pavia, Italy.	Am J Cardiol 2000 May 1;85(9):1114-8 Abstract quote On behalf of the Italian Multicenter Cardiomyopathy Study Group. Excessive ethanol intake is reported in 3% to 40% of patients with idiopathic dilated cardiomyopathy (IDC). In the prevasodilator era, the prognosis was reportedly better in alcoholic than in IDC patients, an advantage limited to abstinent patients. No large series of patients systematically treated with angiotensin-converting enzyme inhibitors has since been described. We analyzed long-term outcome according to alcohol abuse in male patients with IDC. Among 338 men who had been prospectively enrolled in a multicenter registry, 79 (23%) were defined as alcohol abusers and further classified at follow-up as having stopped (AAS) or continued (AAC) abuse. AAC subjects at enrollment reported a higher daily alcohol intake than AAS subjects (178 +/- 113 vs 127 +/- 54 g/day, p = 0.012). During a mean of 59 +/- 35 months, 102 patients died and 45 underwent transplantation. Seven-year transplant-free survival was significantly lower in alcohol abusers (41%) than in patients with IDC (53%, p = 0.026), and significantly lower in AAC subjects (27%) than in either patients with IDC or AAS (45%) (p = 0. 018). Although IDC patients had beneficial changes in left ventricular function at follow-up, only AAS patients had significant improvement in ejection fraction. In this large series of patients treated with angiotensin-converting enzyme inhibitors and prospectively followed up, excessive alcohol intake was found in about one fourth of cases and persistent alcohol abuse correlated with a worse prognosis and function at follow-up.
Alcohol and the heart. Schoppet M, Maisch B. Department of Internal Medicine, Cardiology and Angiology, Philipps University Marburg, Germany.	Herz 2001 Aug;26(5):345-52 Abstract quote ALCOHOLISM IN GENERAL: Alcoholism is one of the major health problems in the world. Alcohol consumption has an impact on different body systems like the central nervous system, the gastrointestinal tract, the hematopoetic organs, and the cardiovascular system. Alcohol interferes with other medications, and drinking can exacerbate a variety of medical illnesses. IMPACT ON THE HEART: In the heart, alcohol and its metabolite acetaldehyde confer a toxic effect on mitochondria as well as on the sarcoplasmatic reticulum, which is dependent on both the mean daily consumption and the duration of alcohol intake. A wide range of toxic effects of alcohol in distinct individuals can be observed and modest doses of alcohol can exert beneficial effects on the cardiovascular system probably by an increase in high density lipoprotein cholesterol (HDL) or changes in blood clotting mechanisms. Detrimental effects of alcohol on the heart comprise a decrease in myocardial contractility, hypertension, atrial and ventricular arrhythmias, and secondary non-ischemic dilated cardiomyopathy. After consuming large quantities of alcohol over years, alcoholic cardiomyopathy may develop, which presents with dilation and impaired contractility of the left or both ventricles. Endomyocardial biopsies of patients with alcoholic cardiomyopathy reveal in up to 30% of all cases myocarditis with lymphocytic infiltrates. TREATMENT: Abstinence after development of milder heart failure can stop progression or even reverse symptoms in some cases, otherwise severe heart failure ensues leading to a poor prognosis. Except abstinence, treatment of alcoholic cardiomyopathy is based on the regimen of therapy for heart failure to reduce the size of the dilated heart and to mitigate the symptoms of heart failure.

 

PATHOGENESIS	CHARACTERIZATION
HYPERTROPHIC
A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy. Varnava A, Baboonian C, Davison F, de Cruz L, Elliott PM, Davies MJ, McKenna WJ. Department of Cardiological Sciences, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.	Heart 1999 Nov;82(5):621-4 Abstract quote AIM: To screen for a mutation of the cardiac troponin T gene in two families where there had been sudden deaths without an increase in left ventricular mass but with myocardial disarray suggesting hypertrophic cardiomyopathy. METHODS: DNA from affected individuals from both families was used to screen the cardiac troponin T gene on an exon by exon basis. Mutation screening was achieved by polymerase chain reaction and direct sequencing. Where appropriate, a mutation was confirmed by restriction digest. RESULTS: A novel missense mutation of exon 9 was found in the affected individuals of one of the families. This mutation at amino acid 94 resulted in the substitution of arginine for leucine and was not found in 100 normal control samples. A mutation of the cardiac troponin T gene was excluded in the second family. CONCLUSIONS: A mutation of the gene for the sarcomeric protein cardiac troponin T can cause familial hypertrophic cardiomyopathy with marked myocyte disarray and frequent premature sudden death in the absence of myocardial hypertrophy at clinical or macroscopic level.
Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene. Kokado H, Shimizu M, Yoshio H, Ino H, Okeie K, Emoto Y, Matsuyama T, Yamaguchi M, Yasuda T, Fujino N, Ito H, Mabuchi H. Second Department of Internal Medicine, School of Medicine, Kanazawa University, Kanazawa, Japan.	Circulation 2000 Aug 8;102(6):663-9 Abstract quote BACKGROUND: Mutations that cause hypertrophic cardiomyopathy (HCM) have been identified in 9 genes that code proteins in the sarcomere. Previous reports have demonstrated that cardiac troponin I (cTnI) gene mutations may account for familial HCM; however, the clinical characteristics and prognosis of patients with HCM caused by cTnI gene mutations are not known. METHODS AND RESULTS: We analyzed cTnI gene mutations in 130 unrelated probands with HCM and their families to clarify the genotype-phenotype correlations. We identified 25 individuals in 7 families with a Lys183 deletion (Lys183 del) mutation in exon 7 of the cTnI gene. The disease penetrance in subjects aged >20 years was 88% by echocardiography and 96% by ECG. Sudden death occurred in 7 individuals of 4 families at any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy-like features. Of affected individuals, 4 of 5 individuals aged >40 years followed by echocardiography showed septal thinning and decreased fractional shortening during >5 years of follow-up. CONCLUSIONS: The Lys183 del mutation in the cTnI gene in patients with HCM is associated with variable clinical features and outcomes. HCM caused by the Lys183 del mutation has a significant disease penetrance. This mutation is associated with sudden death at any age and dilated cardiomyopathy-like features in those aged >40 years. However, it remains unclear whether screening of families with HCM for this mutation will be useful in patient management and counseling.
Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy. Ho CY, Lever HM, DeSanctis R, Farver CF, Seidman JG, Seidman CE. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.	Circulation 2000 Oct 17;102(16):1950-5 Abstract quote BACKGROUND: Mutations in the gene that encode cardiac troponin T (cTnT) account for approximately 15% of cases of familial hypertrophic cardiomyopathy (HCM). These mutations are associated with a particularly severe form of HCM characterized by a high incidence of sudden death and a poor overall prognosis, despite subclinical or mild left ventricular hypertrophy. METHODS AND RESULTS: We evaluated a family with HCM and multiple occurrences of sudden death in children. DNA samples were isolated from peripheral blood or paraffin-embedded tissue, and all protein-encoding exons of the cTnT gene were sequenced. A mutation was identified in exon 11 and is predicted to substitute a phenylalanine-for-serine mutation at residue 179 (Ser(179)Phe) in cTnT. Both parents and 3 of 4 surviving and clinically unaffected children were heterozygous for this mutation; another clinically unaffected child did not carry the mutation. Genetic analysis of DNA from a child who died suddenly at age 17 years demonstrated he was homozygous for this mutation. A review of his echocardiogram revealed profound left and right ventricular hypertrophy. CONCLUSIONS: An homozygous Ser(179)Phe mutation in cTnT causes a severe form of HCM characterized by striking morphological abnormalities and juvenile lethality. In contrast, the natural history of the heterozygous mutation is benign. These studies emphasize the relevance of genetic diagnosis in hypertrophic cardiomyopathy and provide a new perspective on the clinical consequences of troponin T mutations.
Phenotypic variation of familial hypertrophic cardiomyopathy caused by the Phe(110)-->Ile mutation in cardiac troponin T. Lin T, Ichihara S, Yamada Y, Nagasaka T, Ishihara H, Nakashima N, Yokota M. Department of Clinical Laboratory Medicine, Nagoya University School of Medicine, Nagoya, Japan.	Cardiology 2000;93(3):155-62 Abstract quote Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familial hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals, including 6 with HCM, was subjected to genetic and clinical assessment. Five exons of the cTnT gene were sequenced in all family members. A heterozygous or homozygous T(340)-->A (Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was detected in 11 subjects. Morphological and functional evaluation of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderate cardiac hypertrophy. Cardiac hypertrophy and other clinical features in the 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM. Thus, the clinical features of HCM due to the Phe(110)-->Ile mutation in the cTnT gene appear to be modified by a gene dosage effect.
RESTRICTIVE
The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Liao P, Georgakopoulos D, Kovacs A, Zheng M, Lerner D, Pu H, Saffitz J, Chien K, Xiao RP, Kass DA, Wang Y. Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.	Proc Natl Acad Sci U S A 2001 Oct 9;98(21):12283-8 Abstract quote Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP kinase in ventricular myocytes was achieved in vivo by using a gene-switch transgenic strategy with activated mutants of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted in significant induction of p38 kinase activity and premature death at 7-9 weeks. Both groups of transgenic hearts exhibited marked interstitial fibrosis and expression of fetal marker genes characteristic of cardiac failure, but no significant hypertrophy at the organ level. Echocardiographic and pressure-volume analyses revealed a similar extent of systolic contractile depression and restrictive diastolic abnormalities related to markedly increased passive chamber stiffness. However, MKK3bE-expressing hearts had increased end-systolic chamber volumes and a thinned ventricular wall, associated with heterogeneous myocyte atrophy, whereas MKK6bE hearts had reduced end-diastolic ventricular cavity size, a modest increase in myocyte size, and no significant myocyte atrophy. These data provide in vivo evidence for a negative inotropic and restrictive diastolic effect from p38 MAP kinase activation in ventricular myocytes and reveal specific roles of p38 pathway in the development of ventricular end-systolic remodeling.
DILATED
Sudden death in dilated cardiomyopathy. Wu AH, Das SK. Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.	Clin Cardiol 1999 Apr;22(4):267-72 Abstract quote The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.
Human eHAND, but not dHAND, is down-regulated in cardiomyopathies. Natarajan A, Yamagishi H, Ahmad F, Li D, Roberts R, Matsuoka R, Hill S, Srivastava D. Division of Intensive Care, Department of Pediatrics, University of Texas Southwestern Medical Center, University of Texas Southwestern Medical Center, One Baylor Plaza, Dallas, Texas 75390-9148, USA.	J Mol Cell Cardiol 2001 Sep;33(9):1607-14 Abstract quote The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization. RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice, dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.
Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections. Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M, Hetzer R, Lamers J, Schultheiss HP, Poller W. Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Freie Universitat, Berlin, Germany.	Circulation 2001 Jul 17;104(3):275-80 Abstract quote BACKGROUND: The coxsackievirus and adenovirus receptor (CAR) was identified as a common cellular receptor for both viruses, but its biological and pathogenic relevance is uncertain. Knowledge of CAR localization in the human cardiovascular system is limited but important with respect to CAR-dependent viral infections and gene transfer using CAR-dependent viral vectors. METHODS AND RESULTS: Explanted failing hearts from 13 patients (8 with dilated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM]) and normal donor hearts (n=7) were investigated for the expression levels and subcellular localization of CAR and the adenovirus coreceptors alpha(v)beta(3) and alpha(v)beta(5) integrins. CAR immunoreactivity was very low in normal and non-DCM hearts, whereas strong CAR signals occurred at the intercalated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%); these strong signals colocalized with both integrins. In all hearts, CAR was detectable in subendothelial layers of the vessel wall, but not on the luminal endothelial surface, and on interstitial cells. Human CAR (hCAR) expressed in rat cardiomyocytes was targeted to cell-cell contacts, which resembled CAR localization in DCM hearts and resulted in 15-fold increased adenovirus uptake. CONCLUSIONS: Low hCAR abundance may render normal human myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR, such as that observed in DCM, may be a key determinant of cardiac susceptibility to viral infections. Asymmetric expression of hCAR in the vessel wall may be an important determinant of adenovirus tropism in humans. hCAR subcellular localization in human myocardium and hCAR targeting to cell-cell contacts in cardiomyocyte cultures suggest that hCAR may play a role in cell-cell contact formation.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
HYPERTROPHIC
Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease. Varnava AM, Elliott PM, Baboonian C, Davison F, Davies MJ, McKenna WJ. Department of Cardiological Sciences, St George's Hospital Medical School, Cranmer Terrace, London, UK.	Circulation 2001 Sep 18;104(12):1380-4 Abstract quote BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of premature death; this is particularly apparent for patients with mutations of the troponin T gene. Myocyte disarray and interstitial fibrosis, pathological features of HCM, may be determinants in these deaths. The relation between genotype, pathological phenotype, and mode of death has not been explored. METHODS AND RESULTS: Seventy-five hearts with HCM were examined. DNA was available in 50 for screening of the troponin T gene. The macroscopic findings, percentage of disarray, percentage of fibrosis, and percentage of small-vessel disease were correlated with the genotype. A troponin T mutation was identified in 9 of the 50 patients, 8 of whom died suddenly. Patients with a troponin T mutation were younger (mean age, 21.0 years [range, 6 to 37] versus 39.1 years [range, 14 to 72]; P<0.0001), had more sudden death (P=0.02), and had lower heart weights, less fibrosis, and greater disarray than other HCM patients (mean heart weight, 380.3+/-105.4 versus 585.0+/-245.7 g, P=0.002; mean fibrosis, 0.7+/-0.4% versus 2.6+/-2.8%, P=0.001; mean disarray, 46.2+/-7.2% versus 24.1+/-15.9%, P<0.0001; and mean small-vessel disease, 11.7+/-14.6 versus 14.1+/-8.7, P=0.6, respectively). Similarly, patients with troponin T mutations who died suddenly had lower heart weights and greater disarray than patients who died suddenly with unknown genotype (ie, troponin T mutation excluded) (mean heart weight, 429.8+/-75.4 versus 559.6+/-204.43 g, P=0.04, and mean disarray, 40.1+/-9.4% versus 20.2+/-12.6%, P=0.002, respectively). CONCLUSIONS: Patients with troponin T mutations had severe disarray, with only mild hypertrophy and fibrosis. These patients died suddenly and at an especially early age. We propose that extensive myocyte disarray in the absence of marked hypertrophy is the pathological substrate for sudden death in these patients.
RESTRICTIVE
Spectrum of restrictive cardiomyopathy: report of the national survey in Japan. Hirota Y, Shimizu G, Kita Y, Nakayama Y, Suwa M, Kawamura K, Nagata S, Sawayama T, Izumi T, Nakano T, et al. Department of Internal Medicine, Osaka Medical College, Japan.	Am Heart J 1990 Jul;120(1):188-94 Abstract quote This report describes clinical profiles and echocardiographic, hemodynamic, and histologic findings in 26 cases of idiopathic RCM based on the diagnostic criteria of (1) heart failure resulting from a stiff left ventricle, (2) normal LV size and systolic function, (3) absence of LV hypertrophy, and (4) cause or association unknown. There were 14 male and 12 female patients ranging in age from 5 to 63 years. Ten patients died during the mean follow-up period of 145 months, and five died of heart failure after 10 years. Three had a family history of HCM. Thromboembolism was observed in eight. Echocardiograms showed normal LV wall thickness and contraction. Hemodynamic characteristics included elevated biventricular filling pressures and a pulmonary wedge pressure that was usually higher than the right atrial pressure. Equalization of biventricular filling pressures was seen, however, in almost all patients with severe tricuspid regurgitation (seven of eight). The square root sign was seen in 50% in RV diastolic pressure tracings and 28% in LV tracings. This sign was observed in patients with elevated filling pressures. Interstitial fibrosis (22 of 23), endocardial thickening (13 of 23), and myofibrillar hypertrophy (10 of 23) were common histologic findings. Severe myocardial fiber disarray consistent with HCM was seen in four patients.
Idiopathic restrictive cardiomyopathy in childhood. A diastolic disorder characterized by delayed relaxation. Gewillig M, Mertens L, Moerman P, Dumoulin M. Department of Pediatric Cardiology, Gasthuisberg University Hospital, Leuven, Belgium.	Eur Heart J 1996 Sep;17(9):1413-20 Abstract quote Six children with idiopathic restrictive cardiomyopathy were evaluated. Electrocardiographic evaluation disclosed left atrial dilatation and repolarization abnormalities. Echocardiographic examination showed gross left atrial enlargement (182 +/- 29% of predicted values, P < 0.001) in the presence of normal left ventricular cavity dimensions (99 +/- 6%, P: ns). Left ventricular wall thickness varied from normal to mild concentric hypertrophy (septum: 116 +/- 16%, P < 0.05). Global left ventricular systolic function was normal or slightly subnormal; however, the relaxation was significantly delayed throughout diastole. E/A ratio was 4.1 +/- 1.4 and deceleration time 94 +/- 7 ms. Marked ventricular filling occurred in mid-diastole as could be deduced from a prominent mid-diastolic mitral L wave on the Doppler flow tracing. Early filling contributed 56 +/- 6%, mid-diastolic filling 28 +/- 4% and atrial contraction 16 +/- 3% to total ventricular filling as estimated by determining E-area, L-area and A-area, respectively. The left ventricular pressure curve showed a steady decline during mid-diastolic filling. This implies that the driving force for mid-diastolic filling is not the increased left atrial pressure but suction by the ventricle. The restrictive haemodynamics are therefore not caused by increased intrinsic stiffness of the ventricular wall, but most likely result from serious dysfunction and delay of the active relaxation of the ventricle. Progression of the disease was observed in three out of six patients, resulting in death or extreme low cardiac output. The three other patients remained clinically stable during the follow-up period of 6-10 years.
Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Ammash NM, Seward JB, Bailey KR, Edwards WD, Tajik AJ. Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn. 55905, USA.	Circulation 2000 May 30;101(21):2490-6 Abstract quote BACKGROUND: Idiopathic restrictive cardiomyopathy is a poorly recognized entity of unknown cause characterized by nondilated, nonhypertrophied ventricles with diastolic dysfunction resulting in dilated atria and variable systolic function. METHODS AND RESULTS: Between 1979 and 1996, 94 patients (61% women) 10 to 90 years old (mean, 64 years) met strict morphological echocardiographic criteria for idiopathic restrictive cardiomyopathy, mainly dilated atria with nonhypertrophied, nondilated ventricles. None had known infiltrative disease, hypertension of >5 years' duration, or cardiac or systemic conditions associated with restrictive filling. Nineteen percent were in NYHA class I, 53% in class II, and 28% in class III or IV. Atrial fibrillation was noted in 74% of patients and systolic dysfunction in 16%. Follow-up (mean, 68 months) was complete for 93 patients (99%). At follow-up, 47 patients (50%) had died, 32 (68%) of cardiovascular causes. Four had heart transplantation. The death rate compared with actuarial statistics was significantly higher than expected (P<0.0001). Kaplan-Meier 5-year survival was 64%, compared with expected survival of 85%. Multivariate analysis using proportional hazards showed that the risk of death approximately doubles with male sex (hazard ratio [HR] = 2.1), left atrial dimension >60 mm (HR = 2.3), age >70 years (HR = 2.0), and each increment of NYHA class (HR = 2.0). CONCLUSIONS: Idiopathic restrictive cardiomyopathy or nondilated, nonhypertrophic ventricles with marked biatrial dilatation, as defined morphologically by echocardiography, affects predominantly elderly patients but can occur in any age group. Patients present with systemic and pulmonary venous congestion and atrial fibrillation and have a poor prognosis, particularly men >70 years old with higher NYHA class and left atrial dimension >60 mm.
DILATED
Apoptosis in myocarditis and dilated cardiomyopathy: Does enterovirus genome persistence protect from apoptosis? - An endomyocardial biopsy study. Alter P, Jobmann M, Meyer E, Pankuweit S, Maisch B. Department of Internal Medicine and Cardiology, Philipps-University Marburg/Lahn, Baldingerstrasse, D-35033, Marburg, Germany	Cardiovasc Pathol 2001 Sep-Oct;10(5):229-34 Abstract quote The purpose of this study was to examine the role of apoptosis in myocarditis and dilated cardiomyopathy. Apoptosis is an active energy-consuming mechanism of cell death in several cardiac diseases in different quality and quantity. Methods: Endomyocardial biopsies from 81 patients with active (1) and chronic myocarditis (10), dilated cardiomyopathy with inflammation (DCMi; 10) and without inflammation (DCM; 20), with borderline myocarditis and positive PCR for cytomegalovirus-DNA (6), adenovirus-DNA, or enterovirus-RNA (7), and controls (17) were analysed. Apoptosis was detected by using the TUNEL method. The highest rate of apoptotic cardiocytes was found in active and chronic myocarditis. One patient with severe active myocarditis demonstrated 6.15% of apoptotic cardiocytes. Mean percentage of apoptotic cardiocytes in chronic myocarditis was significantly increased (0.61+/-1.25%) when compared to controls (0.01+/-0.04%, P<.05). Particularly, patients with cytomegalovirus-DNA persistence in borderline myocarditis had an elevated rate of apoptosis (0.34+/-0.68%, P<.05). Increased rates of apoptosis were found in borderline myocarditis with adenovirus-DNA persistence (0.20+/-0.57%) and in DCM (0.06+/-0.15%). Only a nonsignificant increase of apoptotic cardiocytes was found in DCMi (0.03+/-0.08%). No apoptosis was found in patients with enteroviral genome persistence in borderline myocarditis. Conclusions: Apoptosis of cardiac cells is increased in myocarditis and dilated cardiomyopathy, being highest in severe active myocarditis. Apoptosis thus contributes to cell death in active myocarditis and may play a role not to be neglected in dilated cardiomyopathy. Enteroviruses seem to have anti-apoptotic effects, because no apoptosis at all was found in the myocardium.
VARIANTS
Arrhythmogenic right ventricular cardiomyopathy: Clinicopathologic correlation based on a revised definition of pathologic patterns Giulia D'Amati, PhD Ornella Leone, MD Cira Rosaria Tiziana di Gioia, PhD, etal.	Hum Pathol 2001;32:1078-1086. Abstract quote Different morphologic features of arrhythmogenic right ventricular cardiomyopathy (ARVC) have been described. However, it is still unclear whether they correspond to distinct forms of the same disease. A pathologic study was performed on a series of ARVC (15 from heart transplant and 12 from autopsy) from 2 Italian referral university hospitals. Based on both myocellular features and the nature of myocardial replacement, hearts were divided into 2 groups: infiltrative, with a lacelike pattern of transmural fatty infiltration and strands of normal residual cardiomyocytes (n = 11); and cardiomyopathic, with massive myocardial replacement by fibro fatty tissue and cardiomyopathic changes (such as hypertrophy and myofibril loss) of residual cardiomyocytes (n = 16). Hearts from the infiltrative group were mostly obtained at autopsy of patients who died suddenly. Fatty substitution was limited almost exclusively to the right ventricle. Mitral valve dysplasia (prolapse or cleft) was frequently present. Hearts from the cardiomyopathic group came mainly from heart transplants for congestive heart failure. Fibro fatty replacement was more extensive, usually biventricular. Active myocarditis and features suggestive of myocardial transdifferentiation were also observed. Despite these differences in clinical outcome and morphologic features, patients from the 2 groups showed similar mean age, sex distribution, occurrence of threatening ventricular arrhythmias, and prevalence of family history of sudden death, arrhythmias, or cardiomyopathy. Infiltrative and cardiomyopathic patterns represent different clinical and pathologic subsets of ARVC. Myocellular features are an important clue in the distinction between the two entities. The differentiation between the 2 patterns is feasible on endomyocardial biopsy and could give important prognostic information.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
HYPERTROPHIC
Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease. Varnava AM, Elliott PM, Sharma S, McKenna WJ, Davies MJ. Department of Cardiovascular Pathology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.	Heart 2000 Nov;84(5):476-82 Abstract quote OBJECTIVE: To make a quantitative assessment of the relation between disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy. DESIGN: Detailed macroscopic and histological examination at 19 segments of the left and right ventricle and the left atrial free wall. PATIENTS: 72 patients with hypertrophic cardiomyopathy who had suffered sudden death or progression to end stage cardiac failure (resulting in death or heart transplantation). MAIN OUTCOME MEASURES: The presence of scarring, atrial dilatation, and a mitral valve impact lesion were noted, and heart weight, wall thickness, per cent disarray, per cent fibrosis, and per cent small vessel disease quantitated for each heart. RESULTS: Within an individual heart the magnitude of hypertrophy correlated with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002). Overall, however, total heart weight related weakly but significantly to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3, p = 0.03), but not to disarray. Disarray was greater in hearts with mild left ventricular hypertrophy (maximum wall thickness < 20 mm) and preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p = 0.02) and hearts without a mitral valve impact lesion (26.3% v 18.9%, p = 0.04), but was uninfluenced by sex. Fibrosis was influenced by sex (7% in male patients and 4% in female, p = 0.04), but not by the presence of an impact lesion. No relation was found between disarray, fibrosis, and small vessel disease. CONCLUSIONS: Myocyte disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein, while fibrosis and small vessel disease are secondary phenomena unrelated to disarray, but modified by factors such as left ventricular mass, sex, and perhaps local autocrine factors.
Relation between myocyte disarray and outcome in hypertrophic cardiomyopathy. Varnava AM, Elliott PM, Mahon N, Davies MJ, McKenna WJ. Department of Cardiovascular Pathology and Cardiological Sciences, St George's Hospital Medical School, London, United Kingdom.	Am J Cardiol 2001 Aug 1;88(3):275-9 Abstract quote Hypertrophic cardiomyopathy (HC) is associated with an increased risk of sudden cardiac death or death from heart failure. Little is known of the pathologic substrate for risk of premature death in this disease. We therefore set out to correlate the pathologic findings with the mode of death and risk profile in 75 patients with HC. Hearts with HC were obtained after death or transplantation. The clinical details were correlated with the macroscopic findings and the percent fibrosis, disarray, and small-vessel disease across 19 sections of each heart. Thirty-nine patients died suddenly, 28 had end-stage heart failure, and 8 died of other causes. Myocyte disarray correlated positively with evidence of ischemia (r = 0.5, p <0.0001), and was greater in patients who died before age 21 years (mean disarray 33% vs 18%, p <0.0001) and in those with an abnormal vascular response to exercise (mean disarray and 30% vs 19%, p = 0.04). Myocardial fibrosis was greater in patients who died in heart failure (mean percent fibrosis was 2.8% versus 0.9%, p = 0.003), and in patients with nonsustained ventricular tachycardia or a high risk fractionation study (4.9% vs 2.7%, p = 0.04, and 6.84% vs 2.8%, p = 0.03, respectively). In conclusion, young patients who die with HC have greater disarray than their older counterparts. In contrast, myocardial fibrosis is the substrate for premature deaths from heart failure and is associated with an increased risk of a primary ventricular arrhythmia.
RESTRICTIVE
Clinical profile and outcome of restrictive cardiomyopathy in children. Lewis AB. Division of Cardiology, Childrens Hospital of Los Angeles, CA 90054-0700.	Am Heart J 1992 Jun;123(6):1589-93 Abstract quote The clinical profile and outcome of idiopathic restrictive cardiomyopathy in a group of eight children are reviewed. There were six girls and two boys. Age at presentation was 4.0 +/- 2.6 years (range 1.3 to 9.5 years). All patients had evidence of congestive heart failure with systemic venous congestion. Right or left atrial enlargement was the most consistent ECG finding and was present in all patients. Left ventricular shortening fraction was normal in five patients, increased in two, and mildly reduced in one. The most striking echocardiographic feature was severe biatrial dilatation in the presence of normal or near-normal ventricular cavity dimensions. Marked elevation of left ventricular end-diastolic pressure was noted in all seven patients undergoing cardiac catheterization (34 +/- 7 torr; range 24 to 40 torr). Right ventricular end-diastolic pressure was elevated but significantly different from left ventricular pressure (18 +/- 7 torr; p less than 0.01). A characteristic early diastolic dip with a rapid rise to an elevated plateau (square root sign) was present in five of seven patients. Median survival was 1.4 years. Six patients died 0.2 to 7.0 years after they were initially seen. The actuarial survival rate 1.5 years after presentation was 44%, decreasing to 29% at 4 years. Restrictive cardiomyopathy has a worse prognosis in children than in adults. In part this may reflect the more advanced symptoms of congestive failure at initial presentation. Pediatric patients should be considered for early cardiac transplantation.
Clinical spectrum of restrictive cardiomyopathy in children. Chen SC, Balfour IC, Jureidini S. Saint Louis University School of Medicine, Department of Pediatrics and Cardinal Glennon Children's Hospital, 1465 South Grand Blvd., St. Louis, MO 63104-1095, USA.	J Heart Lung Transplant 2001 Jan;20(1):90-2 Abstract quote We reviewed the clinical spectrum and possible prognostic factors in 14 children with restrictive cardiomyopathy. The patients were not homogeneous in clinical presentation or morphology. The mortality rate was high: 21.4% at 1 year and 50% at 2 years after presentation. Younger patients with respiratory symptoms, thromboembolism, increased cardiothoracic ratio on chest radiogram or patients with endocardial fibroelastosis appear to have a worse prognosis and orthotopic cardiac transplantation may be indicated.
DILATED
Infantile dilated cardiomyopathy. Relation of outcome to left ventricular mechanics, hemodynamics, and histology at the time of presentation. Matitiau A, Perez-Atayde A, Sanders SP, Sluysmans T, Parness IA, Spevak PJ, Colan SD. Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, Mass. 02115.	Circulation 1994 Sep;90(3):1310-8 Abstract quote BACKGROUND: For patients with acute dilated cardiomyopathy, definition of prognosis and of clinical features predictive of outcome is particularly important due to the availability of cardiac transplantation and other innovative treatment strategies. METHODS AND RESULTS: We reviewed our experience with 24 children under 2 years of age with dilated congestive cardiomyopathy to determine outcome and potential predictive variables. Clinical, serological, ECG, echocardiographic, hemodynamic, and histological findings were analyzed. Idiopathic cardiomyopathy or myocarditis constituted 29% of the patients presenting with congestive heart failure without structural heart disease. Among these patients, 45% recovered completely, 25% survived with persistent left ventricular dysfunction, and 30% died. All except one of the deaths occurred during the first 2 months after presentation. Poorer outcome and higher mortality were associated with a more severely depressed left ventricular ejection fraction and/or a more spherical left ventricular shape at presentation. Histological evidence of myocardial inflammation was a favorable prognostic indicator, whereas histological evidence of endocardial fibroelastosis was associated with a poor outcome. During the recovery phase, diastolic volume fell rapidly. Ventricular mass was elevated from the earliest observations and fell more slowly, with persistent elevation of the mass-to-volume ratio up to 2 years. Function and contractility improved over the first several months in most patients who recovered, although in occasional patients continued improvement was seen for as long as 2 years after presentation. CONCLUSIONS: Histological and echocardiographic features can be used to identify patients at particularly high risk for death. To have any impact on outcome, decisions about cardiac transplantation must be reached rapidly, since almost all deaths occurred within the first 2 months after presentation. Recovery of function is often rapid, but continued improvement may be seen for as long as 2 years.
Prognostic value of posterior wall thickness in childhood dilated cardiomyopathy and myocarditis. Carvalho JS, Silva CM, Shinebourne EA, Redington AN. Department of Paediatric Cardiology, Royal Brompton National Heart and Lung Hospital, London, U.K.	Eur Heart J 1996 Aug;17(8):1233-8 Abstract quote M-mode indices of left ventricular dimension and posterior wall thickness were derived from echocardiograms of children presenting with dilated cardiomyopathy/myocarditis and were related to outcome. Echocardiograms from 16 of 18 children were manually digitized to obtain changes of left ventricular dimension and posterior wall thickness throughout the cardiac cycle. Indices of ventricular function and the ratio of end-diastolic posterior wall thickness to cavity dimensions were obtained. Patients were divided into group I (alive, n = 7), and group II (died, n = 6 or heart transplantation, n = 3) at median follow-up of 25 months. No significant difference was seen for the shortening fraction, the percentage of posterior wall thickening or the normalized peak rate of left ventricular filling. The normalized peak rate of posterior wall thinning was greater in group II. The posterior wall thickness to cavity dimension ratio was higher in group I (median = 0.19) than group II (median = 0.13) (P < 0.005). Five of six survivors, whose ventricular function improved, had ratios > 0.17. All but one with a ratio < or = 0.16 remained with a dilated heart, died or required transplantation (P = < 0.01). A relatively thicker posterior wall (ratio > 0.17) was associated with better prognosis and recovery. This index should be taken into account in decision-making regarding timing for cardiac transplantation.
Idiopathic dilated cardiomyopathy in children: prognostic indicators and outcome. Arola A, Tuominen J, Ruuskanen O, Jokinen E. Department of Pediatrics, University of Turku, Turku, Finland.	Pediatrics 1998 Mar;101(3 Pt 1):369-76 Abstract quote OBJECTIVE: To determine the outcome of Finnish children and adolescents with idiopathic dilated cardiomyopathy (IDCM) and factors that might be useful as prognostic indicators. METHODOLOGY: The clinical profile and course of 62 Finnish children and adolescents (median age, 13 months; range, 1 day to 20 years) with IDCM in 1980 to 1991 were evaluated to detect factors that might predict outcome. Factors studied included age, gender, family history, previous viral illness, and symptoms and signs at presentation. Furthermore, data on serial electrocardiographic, echocardiographic, and chest x-ray examinations, histologic findings, and treatments were analyzed. RESULTS: During a mean (+/-SD) follow-up of 3.9 +/- 4.5 years (range, 1 day to 25 years), 10 patients (16%) recovered, 17 (27%) had residual disease, 4 (6.4%) underwent heart transplantation, and 31 (50%) died. Infants (<1 year of age) and adolescent (>/=15 years of age) male patients with progressing symptoms of left ventricular failure after initiation of medical therapy tended to have the poorest outcome. However, in multivariate analysis, only histologic evidence of endocardial fibroelastosis, clinical signs of right ventricular failure at presentation, and the need for anticoagulative therapy during follow-up, the last an expression of a severely impaired left ventricular systolic function, appeared to be significant predictors of long-term outcome. CONCLUSIONS: Our study confirms that the outcome of children with IDCM still remains poor. However, a group of patients, mainly infants, make a full recovery. Adolescent male patients as well as infants suffering from endocardial fibroelastosis with persisting symptoms of congestive heart failure after initiation of medical therapy tend to have the poorest outcome. These patients need a careful follow-up at short time intervals and, in the case of lacking response to medical treatment with resulting growth failure and/or poor quality of life, should be offered urgent heart transplantation.
Idiopathic dilated cardiomyopathy in children: clinical profile and prognostic determinants. Nogueira G, Pinto FF, Paixao A, Kaku S. Servico de Cardiologia Pediatrica-Hospital de Santa Marta.	Rev Port Cardiol 2000 Feb;19(2):191-200 Abstract quote Idiopathic dilated cardiomyopathy is a severe disease with a high mortality rate in childhood. Its clinical evolution and prognosis are important for the selection of cardiac transplantation candidates. In order to characterize its evolution and identify prognostic factors, the clinical records of 41 children with the diagnosis of idiopathic dilated cardiomyopathy, admitted from January 1985 to December 1997, were reviewed. Survivors (Group I) and deceased (Group II) were separately analyzed, according to the following parameters: age, sex, race, clinical severity, electrocardiographic, echocardiographic and haemodynamic findings. Seven children were excluded from the study: six of them were lost to follow-up and one died from a surgical complication. Of the remaining 34 children, 20 were male (M) and 14 were female (F) (M/F: 1.4). Age range at diagnosis was 7 days to 14 years (median: 1.5 years), and follow-up time was from 18 days to 10.5 years (median: 2.5 years). Eleven (32.3%) children fully recovered, 13 (38.2%) survived with left ventricular dysfunction, and ten (29.4%) died, half of them within the first three months of follow-up. Mortality was 23.5% (8 out of 34 children) during the first year of follow-up and 29.4% (ten out of 34 children) at five years. Unfavorable prognosis was more frequently associated to: 1) clinical severity at the time of presentation; 2) lower mean left ventricular shortening fraction (10 +/- 7% in group II and 13 +/- 5% in group I); 3) occurrence of severe arrhythmia (40% in group II and 3.5% in group I). In this series a group of higher mortality risk was identified, based on some of the analyzed parameters, which should be considered as selection criteria for early heart transplantation.
TREATMENT
Poor survival of patients with idiopathic cardiomyopathy considered too well for transplantation. Stevenson LW, Fowler MB, Schroeder JS, Stevenson WG, Dracup KA, Fond V. Department of Medicine, UCLA Medical Center 90024-1679.	Am J Med 1987 Nov;83(5):871-6 Abstract quote Although the success of cardiac transplantation has encouraged earlier referral of potential candidates, those with mild symptoms of heart failure are frequently considered "too well" for transplantation. Outcome was investigated for 28 patients with non-ischemic dilated cardiomyopathy and ejection fraction of 25 percent or less who were denied transplantation due to lack of severe symptoms. One-year survival without transplantation was 46 percent. Low stroke volume and history of ventricular arrhythmias were independent predictors of early mortality. High risk, defined as either stroke volume of 40 ml or less or history of ventricular arrhythmia, identified 13 of 14 patients who did not survive one year and only one of 12 one-year survivors (p less than 0.001). Low stroke volume predicted hemodynamic failure (p less than 0.05) whereas arrhythmic history predicted sudden death (p less than 0.001). Clinical status improved in only six patients, all of whom had symptom duration of seven or less months at initial evaluation (p less than 0.001). Thus, patients referred to transplantation for dilated cardiomyopathy with an ejection fraction of 25 percent or less have a poor prognosis even if symptoms are mild. Patients with high hemodynamic risk may require early transplantation, whereas those with high arrhythmia risk may require other aggressive therapy in order to avoid transplantation until symptoms become severe.
DILATED
Effect of Beta-Blocker Therapy on Myocardial Perfusion Defects in Thallium-201 Scintigraphy in Patients with Dilated Cardiomyopathy. Hara Y, Inoue K, Ogimoto A, Ohtsuka T, Shigematsu Y, Nakata S, Higaki J. Department of Internal Medicine, Ehime University School of Medicine, Toon City, Japan.	Cardiology. 2005 May 28;104(1):16-21 [Epub ahead of print] Abstract quote   Background: Thebeneficial effects of beta-blocker therapy in patients with heart failure have been confirmed. However, the effects of beta-blockers on myocardial perfusion defects are unclear. The aim of this study was to evaluate the effect of beta-blockers on myocardial perfusion defects estimated by thallium-201 myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to investigate the relationships between beta-blocker treatment and myocardial damage and cardiac function. Methods:(201)Tl and echocardiography were performed in 37 patients before and after 6 months of beta-blocker therapy. Extent score (ES) by (201)Tl was used to quantitate myocardial perfusion defects before and after treatment. Results: ES was significantly decreased by beta-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, beta-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES. Conclusions: beta-Blocker therapy could attenuate myocardial perfusion defects in some patients with DCM. The improvement in left ventricular function associated with beta-blocker therapy may be related to the attenuation in myocardial perfusion defects.
The effect of treatment with angiotensin-converting enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy. Lewis AB, Chabot M. Division of Cardiology, Childrens Hospital Los Angeles, CA 90054-0700.	Pediatr Cardiol 1993 Jan;14(1):9-12 Abstract quote Outcome in 81 pediatric patients with dilated cardiomyopathy was reviewed to assess whether treatment with angiotensin-converting enzyme (ACE) inhibitors affected survival. Age at onset was 3.6 +/- 0.6 years. Twenty-seven children (group 1) were treated with ACE inhibitors. Conventional therapy was used in the remaining 54 patients (group 2). There were no significant differences between the two groups in age at onset, left ventricular shortening fraction, left ventricular end-diastolic pressure, or mean pulmonary artery pressure. Patients treated with ACE inhibitors had a significantly better survival during the first year (p < 0.05) with continuation of this trend throughout the second year (p = 0.06). Beyond 2 years there was a tendency toward better survival in ACE inhibitor-treated patients, but the differences were no longer significant (p = 0.14). These data, along with observations in adult patients with chronic cardiac failure, indicate that converting enzyme inhibitors have a beneficial effect on prolonging survival of infants and children with severe left ventricular dysfunction from dilated cardiomyopathy.
Changing mortality in dilated cardiomyopathy. The Heart Muscle Disease Study Group. Di Lenarda A, Secoli G, Perkan A, Gregori D, Lardieri G, Pinamonti B, Sinagra G, Zecchin M, Camerini F. Department of Cardiology, Ospedale Maggiore and University, Trieste, Italy.	Br Heart J 1994 Dec;72(6 Suppl):S46-51 Abstract quote OBJECTIVE--To analyse the changes in mortality in dilated cardiomyopathy over the past 15 years and to identify the factors that might have influenced survival. DESIGN--Follow up study of 235 patients (aged 16-70) systematically enrolled on a register from 1 January 1978 to 31 December 1992. SETTING--Hospital department of cardiology. PATIENTS--Three groups corresponding to three periods of 5 years: group 1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients; group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients; and group 3 (diagnosis between 1 January 1988 and 31 December 1992) 144 patients. MAIN OUTCOME MEASURES--Death or heart transplantation. RESULTS--Two and four year survival was 73.8% and 53.8% in group 1, 87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02). During the 15 years of the study period the number of cases increased progressively and the baseline clinical characteristics changed (that is, patients were younger and less severely affected), partly explaining the improvement in survival. None the less, the three mortality curves tended to diverge progressively and the improvement in survival in the different groups was still significant after stratification for the severity of the disease, suggesting that treatment had a sustained effect. A progressively higher proportion of patients were treated with angiotensin converting enzyme (ACE) inhibitors and more recently with beta blockers. In group 2, after stratification for the severity of heart failure, patients who were treated with ACE inhibitors showed a better survival than patients who were not. Furthermore, analysis of group 3 showed that beta blockers had a significant additive effect with conventional therapy both by intention to treat and actual treatment. Four year survival in patients with mild and moderate to severe heart failure treated with beta blockers, and usually digitalis and ACE inhibitors, was respectively 90% and 87.5%. CONCLUSIONS--The improvement in the survival of patients with dilated cardiomyopathy over the past 15 years may be explained by earlier diagnosis, new treatments, and a change in the clinical characteristics of the patients at enrolment.
Long-term survival effect of metoprolol in dilated cardiomyopathy. The SPIC (Italian Multicentre Cardiomyopathy Study) Group. Di Lenarda A, De Maria R, Gavazzi A, Gregori D, Parolini M, Sinagra G, Salvatore L, Longaro F, Bernobich E, Camerini F. Department of Cardiology, Ospedale Maggiore and University, Trieste, Italy.	Heart 1998 Apr;79(4):337-44 Abstract quote OBJECTIVE: To evaluate the additive effect of metoprolol treatment on long-term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy. DESIGN: 586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled in a multicentre registry and followed up for a mean (SD) of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose, was added to conventional heart failure treatment in 175 patients. RESULTS: Survival and transplant-free survival at seven years were significantly higher in the 175 metoprolol treated patients than in the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol independently predicted survival and transplant-free survival (relative risk reduction values for all cause mortality and combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association class, left ventricular end diastolic diameter, and pulmonary wedge pressure were also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol treated cases than in 127 controls selected from the entire control cohort and appropriately matched. Metoprolol was associated with a 30% reduction in all cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or transplantation (7% to 41%, p = 0.009). CONCLUSIONS: The addition of metoprolol to standard heart failure treatment, including angiotensin converting enzyme inhibitors, was effective in the long-term, reducing both all cause mortality and transplantation in patients with idiopathic dilated cardiomyopathy.
Outcomes for children with cardiomyopathy awaiting transplantation. Nield LE, McCrindle BW, Bohn DJ, West LJ, Coles JG, Freedom RM, Benson LN. Department of Paediatrics, The Hospital for Sick Children, The University of Toronto School of Medicine, Ontario, Canada.	Cardiol Young 2000 Oct;10(4):358-66 Abstract quote OBJECTIVE: To determine factors associated with outcomes after listing for transplantation in children with cardiomyopathies. BACKGROUND: Childhood cardiomyopathies form a heterogeneous group of diseases, and in many, the prognosis is poor, irrespective of the etiology. When profound heart failure develops, cardiac transplantation can be the only viable option for survival. METHODS: We included all children with cardiomyopathy listed for transplantation between 12/89 and 4/98 in this historical cohort study. RESULTS: We listed 31 patients, 15 male and 16 female, 27 with dilated and 4 with restrictive cardiomyopathy, for transplantation. The median age at listing was 5.7 years, with a range from fetal life to 17.8 years. Transplantation was achieved in 23 (74%), with a median interval from listing of 54 days, and a range from zero to 11.4 years. Of the patients, 14 were transplanted within 30 days of listing. Five patients (16%) died before transplantation. Within the Canadian algorithm, one of these was in the third state, and four in the fourth state. One patient was removed from the list after 12 days, having recovered from myocarditis, and two remain waiting transplantation after intervals of 121 and 476 days, respectively. Patients who died were more likely to be female (5/5 vs. 11/26; p=0.04) and to have been in the third or fourth states at listing (5/5 vs. 15/26; p=0.04). The use of mechanical ventricular assistance, in 10 patients, was not a predictor of an adverse outcome. While not statistically significant, survival to transplantation was associated with treatment using inhibitors of angiotensin converting enzyme, less mitral regurgitation, a higher mean ejection fraction and cardiac index, and lower right ventricular systolic pressure. CONCLUSIONS: Children with cardiomyopathy awaiting transplantation have a mortality of 16% related to their clinical state at the time of listing.
Surgical approaches to dilated cardiomyopathy. Smolens IA, Bolling SF. Section of Cardiac Surgery, University of Michigan, Taubman Health Care Center, 2120D, Box 0348, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0348, USA.	Curr Cardiol Rep 2000 Mar;2(2):99-105 Abstract quote Heart failure is one of the leading causes of hospitalization in the United States today. Congestive heart failure is a chronic progressive disease with the common central element being the remodeling of the cardiac chamber associated with ventricular dilation. Secondary mitral regurgitation is a complication of end-stage cardiomyopathy and is associated with a poor prognosis. Historically, these patients were not considered operative candidates due to the high morbidity and mortality in this patient population. Heart transplantation is now considered the standard of treatment for select patients with end-stage heart disease, however, it is only applicable to a small number of patients. In an effort to address this problem, newer and alternative surgical approaches are evolving, including mitral valve annuloplasty, the Batista myoplasty, and cardiomyoplasty. When these operative techniques that alter the shape of the left ventricle are utilized, in combination with optimal medical management for heart failure, survival is improved and patients can avoid or postpone transplantation.
Outcome while awaiting heart transplantation in children: a comparison of congenital heart disease and cardiomyopathy. Rosenthal DN, Dubin AM, Chin C, Falco D, Gamberg P, Bernstein D. Department of Pediatricsa, Lucile Salter Packard Children's Hospital and Stanford University Hospital, Stanford University, Stanford, California, USA.	J Heart Lung Transplant 2000 Aug;19(8):751-5 Abstract quote BACKGROUND: Outcomes for children who undergo heart transplantation differ for children with congenital heart disease as compared to those with structurally normal hearts. Similar data have not been reported for these groups of patients for the morbidity and mortality associated with waiting for a donor. We report these data. METHODS: A retrospective review was performed for all pediatric patients who were listed for heart transplantation at Stanford from 1977 to 1996, comparing mortality and major morbidity for patients with congenital heart disease and those with cardiomyopathy and structurally normal hearts. RESULTS: There were 96 patients who met study criteria, of whom 67 were successfully transplanted. The median waiting time was 23 days. Survival at 30 days was 93% and at 90 days was 81%, with no difference between groups. Major complications were identified in 38% of patients with structurally normal hearts, vs 9% of patients with congenital heart disease (p < 0.001). CONCLUSIONS: Overall mortality is similar for patients with congenital heart disease and those with structurally normal hearts while listed for heart transplantation, but patients with congenital heart disease have fewer episodes of major morbidity during this time.
Impact of cardiac transplantation on molecular pathology of ET-1, VEGF-C, and mitochondrial metabolism and morphology in dilated versus ischemic cardiomyopathic patients. Aharinejad S, Schafer R, Hofbauer R, Abraham D, Blumer R, Miksovsky A, Traxler H, Pullirsch D, Alexandrowicz R, Taghavi S, Kocher A, Laufer G. Laboratory for Cardiovascular Research, First Department of Anatomy, University of Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria.	Transplantation 2001 Sep 27;72(6):1043-9 Abstract quote Little is known about the long-term impact of cardiac transplantation on activity and modifications of endothelin (ET)-1 system, vascular endothelial growth factor (VEGF), and mitochondrial metabolism and morphology in patients with ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM). Messenger RNA (mRNA) expression levels of ET-1, endothelin converting enzyme (ECE)-1, VEGF-C, carnitine palmitoyltransferase (CPT)-1, and carnitine acetyltransferase (CARAT), as well as the number of normal, edematous, and degenerated mitochondria were assessed in left ventricular biopsies of 21 patients with DCM and 20 with ICM (New York Heart Association class III-IV) before and up to 3 months after cardiac transplantation.