Midwall myocardial fibrosis in Becker-Kiener muscular dystrophy

We report on a 38- year-old man with Becker-Kiener muscular dystrophy (BMD) and dilated cardiomyopathy without clinical symptoms of congestive heart failure who was referred for risk evaluation of sudden cardiac death. The degree of cardiac involvement in BMD varies greatly from no or hardly any cardiac abnormality to severe arrhythmias, dilatative cardiomyopathy and heart failure to heart transplantation or sudden cardiac death. These cardiac abnormalities have been related to replacement of the cardiomyocytes by connecting tissue or fat. In the clinical setting, cardiovascular magnetic resonance (CMR) has been proved to be a valid non-invasive method for obtaining anatomical and structural information of the heart. Furthermore, gadolinium-enhanced CMR can also characterize areas of myocardial fibrosis. Demonstration of extensive areas of fibrosis in an early stage of the disease might be a surrogate marker for an impaired clinical outcome. Therefore, serial CMR examinations starting upon diagnosis of the disease should be considered, as this may lead to an earlier recognition of cardiac involvement and may affect further management of the patient.     

The heart in human dystrophinopathies

Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1-2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. Beta-blockers may be an additional option if indicated.     

Cardiac involvement in Duchenne and Becker muscular dystrophy

Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation, not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction, heart block or malignant arrhythmias. Not only DMD/BMD patients, but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent, due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects, arrhythmias (supraventricular or ventricular), hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction, independently of age of onset or mutation groups. Cardiovascular magnetic resonance (CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies’ patients and carriers that can be observed even if overt muscular disease is absent. Recently, new CMR techniques, such as postcontrast myocardial T1 mapping, have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.     

心脏核磁共振成像技术在肥厚型心肌病中的应用现状及最新进展

Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiomyopathy and the leading cause of sudden death in young people and a major cause of heart failure symptoms at any age.Due to its genetic etiology,there is substantial heterogeneity in the phenotypic expression and clinical course of patients with HCM.Traditionally,two-dimensional echocardiography has been the easiest and reliable technique for establishing a diagnosis of HCM.However,cardiovascular magnetic resonance(CMR)has emerged as a novel,3-dimensional tomographic imaging technique,which provides high spatial and temporal resolution images of the heart (not limited by thoracic or pulmonary parenchyma),in any plane and without ionizing radiation.As a result,CMR is particularly well suited to provide detailed characterization of the HCM phenotype,including a precise assessment of the location and distribution of LV wall thickening(as well as other myocardial structures such as the right ventricle and papillary muscles).In this regard,CMR has been demonstrated to provide a diagnosis of HCM in cases where the echocardiogam was non-diagnostic.Furthermore,CMR provides an accurate assessment of total LV mass which is a more robust marker of hypertrophy,with potential implications for risk stratification.In addition,with the intravenous administration of gadolinium,first-pass perfusion sequences can identify myocardial perfusion abnormalities,while late gadolinium enhancement sequences can identify areas of myocardial fibrosis/scarring.Although the clinical implications of late gadolinium enhancement in HCM are still uncertain this information may,in the near-future,have important implications with regard to identifying HCM patients at high risk of sudden death and progressive heart failure,including evolution into the end-stage phase of HCM.Therefore,at present,CMR provides important information impacting on diagnosis and clinical management strategies in patients with HCM and will likely have an expanding role in the evaluation of patients with this complex disease.     

Imaging Interstitial Fibrosis,Left Ventricular Remodeling,and Function in Stage A and B Heart Failure

Myocardial interstitial fibrosis is part of the advanced disease stage of most cardiovascular pathologies. It has been characterized histologically in various disease settings from hypertensive heart disease and diabetic cardiomyopathy to severe aortic stenosis. It is also involved in the process of aging. In cardiovascular medicine, myocardial interstitial fibrosis is associated with several adverse outcomes, especially heart failure (HF) and sudden cardiac death. Until recently, clinical measures of interstitial fibrosis could only be made by invasive myocardial biopsy. The availability of cardiac magnetic resonance (CMR) T1 mapping techniques allows for the indirect measurement of interstitial space characteristics and extracellular volume size, which is closely correlated with collagen content and interstitial infiltration by amyloid and other molecules. There has been significant improvement in the accuracy and reproducibility of T1 acquisition sequences in the last decade; however, the correct use of this technique requires a solid CMR expertise in daily imaging practice. CMR has become the gold standard to assess left ventricular (LV) remodeling and functional features associated with interstitial fibrosis. These features can be detected in the early stages of HF. The main objective of this paper is to review the relevant results of preclinical and clinical observational studies that demonstrate the prognostic impact of interstitial fibrosis assessed by T1 mapping, as well as adverse left ventricular remodeling, as determinants of HF. Therefore, this review focuses on the pathological mechanisms underlying LV remodeling and interstitial fibrosis, in addition to the technical considerations involved in the assessment of interstitial LV fibrosis by CMR. It provides a thorough review of clinical evidence that demonstrates the association of interstitial fibrosis and other-CMR derived LV phenotypes with Stages A and B HF.     

Importancia de los hallazgos de la resonancia magnética cardiaca en el diagnóstico de la miocardiopatía arritmogénica del ventrículo izquierdo

Introduction and objectivesLeft dominant arrhythmogenic cardiomyopathy (LDAC) has recently been recognized as falling on the spectrum of arrhythmogenic cardiomyopathy. It is characterized by fibroadipose replacement of the left ventricle. The aim of this study was to describe the most frequent forms of clinical presentation of LDAC, imaging findings, and events at follow-up, highlighting the importance of cardiac magnetic resonance (CMR).MethodsProspective registry of patients with findings compatible with LDAC. CMR image analysis and clinical follow-up was performed. The primary endpoint was the appearance of major adverse cardiovascular events (MACE) during follow-up, defined as sudden cardiac death, sustained ventricular arrhythmias, and heart transplant.ResultsWe included 74 consecutive patients (mean age, 48.6 years; 50 men [67.6%]). The most frequent CMR indications were chest pain with normal coronary angiography, ventricular arrhythmias, and suspicion of cardiomyopathies. The main CMR findings were midwall and/or subepicardial pattern of late gadolinium enhancement (91.9%), fatty epicardial infiltration (83.8%), and left ventricle segmental contractility abnormalities (47.9%). At a mean follow-up of 3.74 years, 24 patients (32.4%) had a MACE (sudden cardiac death 8.1%, sustained ventricular arrhythmias 21.6%, and heart transplant 4.1%). Independent predictors for the appearance for MACE were a CMR study showing severe late gadolinium enhancement, male sex, and practicing sports.ConclusionsCMR is a key tool for diagnosing LDAC. Characteristic findings are subepicardial fatty infiltration and midwall-subepicardial late gadolinium enhancement. The prognosis of this population is poor with a high incidence of sudden cardiac death and ventricular arrhythmias.     

Progression of Myocardial Fibrosis in Nonischemic DCM and Association With Mortality and Heart Failure Outcomes

ObjectivesThe purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes.BackgroundMyocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM.MethodsIn total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant.ResultsOn CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase >1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p < 0.01), in 60% of these cases the change in LVEF was minimal (<5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p < 0.01) and heart failure–related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p < 0.01) after adjustment for clinical covariates including LVEF.ConclusionsOnce myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.     

“Malignant” hypertrophic cardiomyopathy: Identification of a subgroup of families with unusually frequent premature death

Eight families were identified in which premature cardiac death due to hypertrophic cardiomyopathy occurred with unusual frequency. A total of 69 first degree relatives in the eight families were studied; 41 relatives had evidence of hypertrophic cardiomyopathy and 31 (75 percent) died of their heart disease. Eighteen of these 31 patients were less than 25 years of age at the time of death. Death was sudden and unexpected in 23 of the 31 patients; in 15 of these 23 patients sudden death was the initial manifestation of cardiac disease. The remaining eight patients (seven were from two families) died after a chronic cardiac illness characterized by congestive heart failure, atrial fibrillation or thromboembolic events.

Hence, premature cardiac death occurs frequently in certain families with hypertrophic cardiomyopathy. Such deaths are usually sudden, often occur in previously asymptomatic subjects and are common in children and young adults. These findings suggest that some families may manifest an unusually virulent expression of hypertrophic cardiomyopathy. Although this study cannot establish the precise prevalence with which “malignant” hypertrophic cardiomyopathy occurs, such families appear to be uncommon.     

Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy.

OBJECTIVES: We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. BACKGROUND: Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. METHODS: Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. RESULTS: Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. CONCLUSIONS: In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy.     

Arrhythmogenic right ventricular cardiomyopathy: Perspectives on disease

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown cause. It can cause both cardiac arrhythmia and heart failure or sudden death. As such patients typically will present to one of three groups depending upon the symptoms at presentation: the pathologist, the physician or the arrhythmologist. Typically a young patient who presents with presyncope or syncope may be investigated by an electrophysiologist and have ventricular tachyarrhythmias. Sadly some young individuals with ARVC may present to a pathologist with sudden cardiac death. Those that survive repeated bouts off arrhythmia and/or some individuals with primary heart failure may initially present to general physicians/cardiologists.With the introduction of molecular genetic studies a wider spectrum of disease manifestation has become apparent for Hypertrophic cardiomyopathy (HCM). Different clinical forms of ARVC have been described as having different genetic loci possibly reflecting phenotypic and genetic heterogeneity. Genetic studies have highlighted the difficulties of variable and age-related penetrance for HCM this appears to also be true of ARVC. From the various perspectives it can be seen that ARVC encompasses a complex and variable disease. Over the last decade ongoing research has allowed a much greater understanding of ARVC. Initially arrhythmia was highlighted as the primary disease manifestation, but it has been shown ARVC is a progressive disease, which may present with heart failure or sudden death. As research continues to unravel the complexities of both genetic and environmental factors responsible for variable disease presentation and modification, improvements should also be possible in terms of diagnostic specificity and therapy.     

Early manifestation of myocardial involvement in systemic sclerosis

IntroductionSystemic sclerosis (SSc) is a systemic autoimmune disease involving multiple organs. We present a rare case of SSc in which clinical manifestations of cardiac fibrosis occurred early in the disease course.Case reportWe report the case of a 40-year-old Caucasian man, previously diagnosed with SSc, who presented with decompensated heart failure. Transthoracic echocardiography was remarkable for severe right ventricular systolic dysfunction, abnormal ventricular septal motion, severe functional tricuspid regurgitation and normal pulmonary artery systolic pressure. Left ventricular ejection fraction was 45%. Right heart catheterization revealed no signs of pulmonary hypertension. Cardiac magnetic resonance (CMR) showed diffuse myocardial infiltration, later confirmed as myocardial fibrosis by endomyocardial biopsy.ConclusionsMyocardial fibrosis is an important cause of early heart failure in SSc patients and is associated with poor prognosis. Echocardiography and CMR help establish the diagnosis and enable an appropriate therapeutic strategy to be developed in such cases.     

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

Fabry disease (FD) is an X‐linked lysosomal storage disorder caused by pathogenic variants in the α‐galactosidase A (GLA) gene that leads to reduced or undetectable α‐galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD‐related heart disease and expert consensus recommendations for its management.     

Cardiac involvement in Becker muscular dystrophy

The present review gives an overview of the clinical and subclinical manifestations of cardiac involvement (CI) in Becker muscular dystrophy (BMD), its pathophysiological background, diagnostic possibilities and therapeutic options for CI in BMD patients and carriers. CI may be subclinical or symptomatic. Up to 100% of patients develop subclinical CI. The onset of symptomatic CI is usually in the third decade of life, rarely in the first decade. One-third of patients develop dilative cardiomyopathy with concomitant heart failure. In BMD patients, CI manifests as electrocardiographic abnormalities, hypertrophic cardiomyopathy, dilation of the cardiac cavities with preserved systolic function, dilative cardiomyopathy or cardiac arrest. There is no correlation between CI and the severity of myopathy. CI is more prominent in patients than carriers. As soon as the diagnosis of BMD is established, a comprehensive cardiac examination should be performed. Because CI in BMD is progressive and adequate therapy is available, cardiac investigations need to be regularly repeated. If CI in BMD is recognized early, appropriate therapy may be applied early, resulting in a more favourable outcome.     

Nonobstructive Hypertrophic Cardiomyopathy with Left Ventricular Aneurysm: The Role of Cardiac Magnetic Resonance

Hypertrophic cardiomyopathy with concomitant left ventricular aneurysm is rare and has important clinical implications, including an increased risk of sudden cardiac death. Most patients with this rare combination have obstructive hypertrophic cardiomyopathy, but we treated a 26-year-old woman who had nonobstructive hypertrophic cardiomyopathy and a family history of probable sudden cardiac death. In our patient, coronary angiograms showed distal occlusion of the left anterior descending coronary artery. Late gadolinium-enhanced cardiac magnetic resonance images showed scattered fibrosis within and beyond the left ventricular aneurysm. Precautionary therapy with an implantable cardioverter-defibrillator yielded an uneventful outcome. Cardiac magnetic resonance has emerged as a promising method for diagnosing these aneurysms and detecting associated myocardial fibrosis, thereby enabling patient risk stratification and the determination of appropriate therapeutic options. We discuss the role of cardiac magnetic resonance imaging in the management of this rare clinical entity.Key words: Cardiomyopathy, hypertrophic, familial/complications/pathology/therapy; coronary aneurysm/complications/diagnosis/therapy; death, sudden, cardiac/etiology; defibrillators, implantable; gadolinium/diagnostic use; image enhancement/instrumentation/methods; magnetic resonance imaging; risk assessmentNonobstructive hypertrophic cardiomyopathy (HCM) with left ventricular (LV) apical aneurysm is a rare clinical entity for which diagnostic, prophylactic, and therapeutic approaches are evolving. We describe the case of a patient who was diagnosed with this combination of conditions, and we discuss the role of cardiac magnetic resonance (CMR) in the therapeutic management of such patients.     

Chagas cardiomyopathy and heart failure: From epidemiology to treatment

Chagas disease is among the neglected tropical diseases recognized by the World Health Organization that have received insufficient attention from governments and health agencies.Chagas disease is endemic in 21 Latin America regions. Due to globalization and increased migration, it has crossed borders and reached other regions including North America and Europe. The clinical presentation of the disease is highly variable, from general symptoms to severe cardiac involvement that can culminate in heart failure. Chagas heart disease is multifactorial, and can include dilated cardiomyopathy, thromboembolic phenomena, and arrhythmias that may lead to sudden death. Diagnosis is by methods such as enzyme-linked immunosorbent assay (ELISA) and the degree of cardiac involvement should be investigated with complementary exams including ECG, chest radiography and electrophysiological study. There have been insufficient studies on which to base specific treatment for heart failure due to Chagas disease. Treatment should therefore be derived from guidelines for heart failure that are not specific for this disease. Heart transplantation is a viable option with satisfactory success rates that has improved survival.     

Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance

OBJECTIVES: We sought to assess whether hyperenhancement by gadolinium cardiovascular magnetic resonance (CMR) occurs in hypertrophic cardiomyopathy (HCM) and correlates with the risk of heart failure and sudden death. BACKGROUND: The myocardial interstitium is abnormal in HCM at post-mortem. Focally increased interstitial myocardial space appears as hyperenhancement with gadolinium CMR. METHODS: In a blinded, prospective study, HCM patients were selected for the presence (n = 23) or absence (n = 30) of an increased clinical risk of sudden death and/or progressive adverse left ventricular (LV) remodeling. Gadolinium-enhanced CMR was performed. RESULTS: Myocardial hyperenhancement was found in 42 patients (79%), affecting 10.9% (range 0% to 48%) of the LV mass. There was a greater extent of hyperenhancement in patients with progressive disease (28.5% vs. 8.7%, p < 0.001) and in patients with two or more risk factors for sudden death (15.7% vs. 8.6%, p = 0.02). Improved discrimination was seen in patients >40 years old (29.6% vs. 6.7%, p < 0.001) for progressive disease and for patients <40 years old for risk factors for sudden death (15.7% vs. 2.1%, p = 0.002). Patients with diffuse rather than confluent enhancement had two or more risk factors for sudden death (87% vs. 33%, p = 0.01). CONCLUSIONS: Gadolinium CMR reveals myocardial hyperenhancement in HCM. The extent of hyperenhancement is associated with progressive ventricular dilation and markers of sudden death.     

Confirmation of Chagas' cardiomyopathy following heart transplantation

We report a case of Chagas' cardiomyopathy confirmed in a patient after heart transplantation. The patient initially presented with symptoms of congestive heart failure and was found to have positive serology for prior Trypanosoma cruzi infection. Despite optimal medical management, the patient had deterioration of his cardiac function and he underwent heart transplantation. Pathology examination of the explanted heart confirmed Chagas' cardiomyopathy. The cardiac sequelae of Chagas' disease include arrhythmias, aneurysm, thromboembolism, cardiomyopathy, and sudden death. We review the epidemiology, cardiac pathology, and evaluation of patients with Chagas' cardiac disease. We discuss the clinical features of Chagas' cardiomyopathy and available treatments including cardiac transplantation.     

Arrhythmogenic cardiomyopathy of left ventricle. A rare event,but possible

Arrhythmogenic right ventricular dysplasia (ARVD) is a form of inherited cardiomyopathy characterized by fibro-fatty substitution mainly right ventricular (RV). Affected patients may succumb to life-threatening ventricular arrhythmias and heart failure. It is even more common among athletes who experience sudden cardiac death (SCD). The disease involvement is not limited only to the RV, but the left ventricle (LV) can also be involved. We have reported a case of a 38 years-old man, with two episodes of syncope in his history. After echocardiographic investigations, the patient was referred to cardiovascular magnetic resonance (CMR). Morphological images showed fatty infiltration of the epicardial layer of LV lateral wall (mid and apical segment). A diagnosis of ‘Isolated Left-Sided Arrhythmogenic Cardiomyopathy’ was made. An ICD implantation was performed, and a medical therapy with enalapril and bisoprolol was started.     

Primary restrictive cardiomyopathy: clinical and pathologic characteristics

Twenty-four patients with restrictive cardiomyopathy were identified at St. Thomas' Hospital during a 17-year period. All had endomyocardial biopsy, but in two patients the biopsy specimens were small and nondiagnostic. Seven patients had amyloidosis and five had other specific heart muscle diseases. The remaining 10 patients with primary restrictive cardiomyopathy had myocyte hypertrophy or interstitial fibrosis, or both. Patients with primary restrictive cardiomyopathy presented earlier but survived longer after presentation than did those with amyloidosis. In each group, survival after cardiac catheterization was related to cardiac index but not to filling pressures. Primary restrictive cardiomyopathy was associated with complete heart block in four patients, two of whom had skeletal myopathy. One had a family history of dominantly inherited skeletal myopathy. Primary restrictive cardiomyopathy was present in a mother and daughter. Two other patients had a family history of heart failure, sudden death or complete heart block, alone or in combination, at a young age. Restrictive hemodynamics and complete heart block were present in patients even in the absence of significant fibrosis. The data suggest that primary restrictive cardiomyopathy may be a distinct myopathy with dominant inheritance and incomplete penetrance that is expressed morphologically as myocyte hypertrophy and interstitial fibrosis. Skeletal myopathy may be associated with the cardiomyopathy.