Primary Restrictive Cardiomyopathy Research Articles

Kiosk 6Q-FA-02 - A Rare Case of Primary Restrictive Cardiomyopathy Caused by a Titin Mutation

Kiosk 6Q-FA-02 - A Rare Case of Primary Restrictive Cardiomyopathy Caused by a Titin Mutation

P096: Polymorphisms in SETD7 may predispose the risk of developing late cardiac side effects after radiotherapy including the mediastinum in Hodgkin’ s lymphoma.

Background: In Hodgkin’s lymphoma (HL) radiation therapy including the mediastinum is known to cause long time cardiac side effects. Method: A cohort of 183 previous HL patients who received radiotherapy involving the mediastinum during the period of 1965–1995 were dichotomized into patients with or without known cardiac complications. This was done after a separate study visit performed with a range of 13–43 years from diagnosis (median 23 years). A complication was defined as having a medical record of any of the following clinical conditions: angina, myocardial infarction, congestive heart failure or valvular disease. DNA was extracted from whole blood and analyzed using Infinum OncoArray-500K. We analyzed a set of 4341 single nucleotide polymorphisms (SNPs) representing 167 genes previously associated with late side effects of radiotherapy or associated with the normal myocyte function, ischemic heart disease, primary restrictive cardiomyopathy or valvular disease. The association between cardiac status and alterations in SNPs was examined. Forty-six of the patients had also received doxorubicin, an anthracycline associated with late cardiotoxic side effects. Results: A SNP of SETD7 (intron), rs2725790, significantly differed between the two groups (allelic test, p = 9.2E-6, maxT permutation test p=0.024, logistic regression p=0.00013). To take prior anthracycline therapy into account, logistic regression was performed adjusting for anthracycline therapy (logistic regression p=0.00020). Conclusion: This study indicates that constitutional differences in SETD7, a gene associated with epigenetic regulation of cardiomyogenesis and response to cardiac hypoxia may be involved in the risk of developing late cardiac side effect after radiation therapy of the mediastinum in the treatment of HL.

Genetic Insights into Primary Restrictive Cardiomyopathy.

Restrictive cardiomyopathy is a rare cardiac disease causing severe diastolic dysfunction, ventricular stiffness and dilated atria. In consequence, it induces heart failure often with preserved ejection fraction and is associated with a high mortality. Since it is a poor clinical prognosis, patients with restrictive cardiomyopathy frequently require heart transplantation. Genetic as well as non-genetic factors contribute to restrictive cardiomyopathy and a significant portion of cases are of unknown etiology. However, the genetic forms of restrictive cardiomyopathy and the involved molecular pathomechanisms are only partially understood. In this review, we summarize the current knowledge about primary genetic restrictive cardiomyopathy and describe its genetic landscape, which might be of interest for geneticists as well as for cardiologists.

Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies.

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

P645 Familial restrictive cardiomyopathy and Noonan"s syndrome: a rare association

Abstract Background Noonan syndrome is a rare genetic disorder. Typical cardiac involvement include pulmonary stenosis and hypertrophic cardiomyopathy. We present the association of Noonan syndrome with familial non-hypertrophic cardiomyopathy with haemodynamic features of restrictive physiology. Case description. A 30-year old male patient presented to the outpatient clinic with clinical symptoms of heart failure which was slowly progressive since age 20. He was found to have features of restrictive cardiomyopathy aged 12 years at the time when his mother was diagnosed with Noonan syndrome and restrictive cardiomyopathy. On examination, his 1st and 2nd heart sounds were normal, however 3rd heart sound was present. Pulse was regular, 75 per minute, BP 110/70 mmHg. Chest was clear and saturation 98%. Echocardiography showed small left ventricle (LV) with preserved ejection fraction (EF), borderline LV wall thickness (10-11 mm), restrictive filling pattern with mitral valve E/A ratio 4.2 and deceleration time 68 ms; dilated both atria; and pulmonary artery systolic pressure of 37 mmHg (Figure, panels A-C; F). Prominent late diastolic reversal flow was noted in hepatic veins (Panel D). LV longitudinal strain was borderline in absolute value (-18%) however demonstrated ‘apical sparing’ pattern (Panel E). The right ventricle was small in size with mild hypertrophy and dynamic function, but normal flow through pulmonary valve. Prominent diastolic reversal flow was also noted in superior vena cava. Cardiac magnetic resonance confirmed echocardiographic findings and additionally demonstrated prominent trabeculations and myocardial crypts in the LV, small pericardial effusion; no signs of amyloidosis, myocardial infarction, infiltration or fibrosis. Right heart catheterisation showed borderline pulmonary hypertension with a mean pressure of 25 mmHg, raised pulmonary artery wedge pressure 18 mmHg, normal pulmonary vascular resistance 1.9 WU, and a ‘square root sign’ (Panel G). Patient underwent cardiopulmonary exercise testing, he stopped after 9 mins of Bruce protocol due to fatigue, reaching the Peak VO2 of 21.1ml/kg/min (49% of predicted value). No ST changes or arrhythmic events were noted. Patient was diagnosed with primary (non-infiltrative) familial restrictive cardiomyopathy and discussed at multidisciplinary team meeting with recommendation of close follow-up for timing for heart transplantation. Meanwhile he was encouraged to continue treatment with ramipril and start regular physical activity. Discussion There are only few reports describing familial non-hypertrophic cardiomyopathy in patients with Noonan syndrome and none in their family members. We review typical clinical and diagnostic features of restrictive cardiomyopathy involving both ventricles and raise awareness of clinicians of primary familial restrictive cardiomyopathy as a possible cardiac manifestation in patients with Noonan syndrome and their immediate family members. Abstract P645 Figure.

Multiparametric cardiac magnetic resonance imaging (CMR) for the diagnosis of Loeffler\u2019s endocarditis: a case report

BackgroundEndocarditis parietalis fibroplastica Löfflein (EPF) is a rare form of primary restrictive cardiomyopathy with poor prognosis. It is generally caused by hypereosinophilic syndrome with eosinophilic penetration of the heart. This leads to congestive heart failure in three different stages. As a frequent manifestation of neoplastic diseases, cardiac involvement means poor prognosis.Case presentationThe present report deals with a case of EPF caused by non-specified T-cell lymphoma (T-NOS). Besides an elevated Troponin-T enzyme, the electrocardiogram and the transthoracic echocardiography did not show any characteristic results. Due to risk/benefit assessment and low thrombocyte amounts, endomyocardial biopsy and catheterization were discarded. Using cardiovascular magnetic resonance (CMR) with steady-state free precession sequences, T2-mappping, strain analysis and late gadolinium enhancement, we were able to clearly highlight cardiac involvement at different stages. These findings characterized T-NOS as a palliative situation.ConclusionMultiparametric CMR can not only identify EPF but also characterize the patchy disease state. This provides an individual prognosis assessment. Aside from prognosis estimation, it can also be used for therapy monitoring.

Loeffler's endocarditis—A case report

Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy. We report the case of a young woman with pleuritic chest pain associated with fever and hypereosinophilia. She was hospitalized with suspected acute myopericarditis and was treated with aspirin, leading to clinical improvement. Ten days after discharge, she was rehospitalized due to recurrence of chest pain. The echocardiogram showed what appeared to be a mass filling the apex of the right ventricle (RV). She was referred for magnetic resonance imaging, which revealed marked myocardial thickening in the apex of the RV. The patient underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic endocarditis. After treatment with prednisolone, all symptoms and the eosinophilia disappeared, and there was complete remission of the RV abnormalities. After three years of follow-up, the patient remains asymptomatic. This case shows that, even without an etiologic diagnosis of eosinophilia, the prognosis for Loeffler's endocarditis can be favorable if treatment is initiated early.

Endomiocardite de Löffler – a propósito de um caso clínico

Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy. We report the case of a young woman with pleuritic chest pain associated with fever and hypereosinophilia. She was hospitalized with suspected acute myopericarditis and was treated with aspirin, leading to clinical improvement. Ten days after discharge, she was rehospitalized due to recurrence of chest pain. The echocardiogram showed what appeared to be a mass filling the apex of the right ventricle (RV). She was referred for magnetic resonance imaging, which revealed marked myocardial thickening in the apex of the RV. The patient underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic endocarditis. After treatment with prednisolone, all symptoms and the eosinophilia disappeared, and there was complete remission of the RV abnormalities. After three years of follow-up, the patient remains asymptomatic. This case shows that, even without an etiologic diagnosis of eosinophilia, the prognosis for Loeffler's endocarditis can be favorable if treatment is initiated early.

Cardiac magnetic resonance in tropical endomyocardial fibrosis

Endomyocardial fibrosis (EMF) is a common cause of primary restrictive cardiomyopathy (RCM) in the tropics. Available studies on the role of CMR in diagnostic evaluation of EMF are confined to case reports. We describe the spectrum of CMR features in a group of patients with this disease.

Acute right ventricular failure after pediatric cardiac transplant: Predictors and long-term outcome in current era of transplantation medicine

To identify pretransplant factors associated with postprocedural right ventricular failure and the relationship between right ventricular failure and long-term survival in children. Records were reviewed for children having heart transplantation from 2000 to 2006. Right ventricular failure was identified by clinical and echocardiographic parameters in 33/129 (25%) recipients: dilated cardiomyopathy in 14/90 (15%), congenital heart disease in 11/27 (41%), and restrictive cardiomyopathy in 8/12 (66%). In 9 of 12 (75%), known elevated (reactive) pulmonary vascular resistance progressed to right ventricular failure. In a further 23/117 (20%) recipients, pulmonary vascular resistance within predefined acceptable range progressed to right ventricular failure. Multiple logistic regression analyses indicated elevated pulmonary vascular resistance (odds ratio 12.30; 95% confidence interval 2.73, 55.32; P = .001) and primary diagnosis, restrictive cardiomyopathy (odds ratio 9.21; 95% confidence interval 2.07, 41.12; P = .004), and congenital heart disease (odds ratio 4.07; 95% confidence interval 1.36, 12.19; P = .012) were strongly associated with right ventricular failure, but duration of heart failure, pretransplant mechanical support, donor status, and ischemic times were not. Treatment included inhaled nitric oxide in 28 (84%), mechanical support in 10 (31%), hemofiltration in 13 (40%), and retransplantation in 2. A Cox multiple regression model including: primary diagnosis, right ventricular failure, and elevated pulmonary vascular resistance indicated that only the latter was independently linked with eventual mortality (hazards ratio 5.45; 95% confidence interval 1.36, 21.96; P = .017). Primary diagnosis and pretransplant elevated reactive pulmonary vascular resistance are both linked to the evolution of right ventricular failure. Pulmonary vascular resistance assessment in end-stage heart failure is challenging; therefore, avoidance of right ventricular failure may not always be possible. Aggressive early treatment may mitigate the effects of right ventricular failure: pretransplant elevated pulmonary vascular resistance was independently associated with long-term survival, but right ventricular failure was not.

Echocardiographic Evaluation of Diastolic Function Can Be Used to Guide Clinical Care

For normal cardiac performance, the left ventricle (LV) must be able to eject an adequate stroke volume at arterial pressure (systolic function) and fill without requiring an elevated left atrial (LA) pressure (diastolic function). These systolic and diastolic functions must be adequate to meet the needs of the body both at rest and during stress. Response by Tschope and Paulus on p 809 Systolic function is conveniently (although not always accurately) measured as the ejection fraction (EF), calculated as stroke volume divided by end-diastolic volume.1 The LV EF is easily interpreted. The lower limit of normal is ≈50%. The lower the EF is, the greater the reduction in systolic function. Diastolic function has been more difficult to evaluate.2 Traditionally, invasive measures of LV diastolic pressure-volume relations and the rate of LV pressure fall during isovolumetric relaxation have been used. However, these methods are not practical for routine clinical use and do not adequately evaluate all aspects of diastolic filling.3 Comprehensive echocardiographic evaluation of the dynamics of LV filling using blood pool and tissue Doppler has now progressed so that it provides clinically important information that can be used to direct patient care. We present data that support the use of echocardiographic evaluation of diastolic function to recognize cardiac dysfunction in patients with heart failure, especially those with preserved EF; to guide the management of patients by identifying those with and without elevated left filling pressures regardless of underlying EF; and to determine prognosis in a wide variety of patient populations. Although the LV end-diastolic pressure-volume relation describes the passive properties of the LV, LV filling is not a passive or slow process.3 In fact, the peak flow rate across the mitral valve is equal to or greater than the peak flow rate across the aortic valve. …

The 2006 American Heart Association Classification of Cardiomyopathies Is the Gold Standard

The cardiomyopathies are an important and complex group of heart muscle diseases with multiple etiologies and heterogeneous phenotypic expression.1 Awareness and knowledge of these diseases in both the public and medical communities have historically been impaired by periodic confusion surrounding definitions and nomenclature. Therefore, formal and systematic classifications have traditionally been viewed as useful exercises promoting greater understanding of the heart muscle diseases.1–10 Indeed, a multitude of such cardiomyopathy classifications have been advanced over the years by individual investigators and consensus panels sanctioned by medically related organizations such as the World Health Organization (WHO).2,4 These classification schemes have evolved in concert with the level of scientific understanding. Response by Elliott p 76 Remarkably, it was not until 50 years ago (1957) that the term cardiomyopathy was used for the first time.1 Over the next 25 years, a number of definitions for cardiomyopathies were advanced. Indeed, in the original 1980 WHO classification,4 cardiomyopathies were defined only as “heart muscle diseases of unknown cause,” reflecting a general lack of available information about basic disease mechanisms. In 1968, the WHO defined cardiomyopathies as “diseases of different and often unknown etiology in which the dominant feature is cardiomegaly and heart failure.”1,3 The final WHO classification published in 19952 proposed “diseases of myocardium associated with cardiac dysfunction” and included for the first time arrhythmogenic right ventricular cardiomyopathy/dysplasia, as well as primary restrictive cardiomyopathy. Therefore, why was it necessary to offer yet another classification scheme for cardiomyopathies in 2006 under the auspices of the American Heart Association (AHA)1? In fact, the international expert consensus panel (and writing group) found several very important reasons to take on this project. The last formal effort at developing a consensus for the classification of cardiomyopathies had been published 12 years previously …

Revisiting definition and classification of cardiomyopathies in the era of molecular medicine

Primary myocardial diseases have always attracted the attention of the scientific community because of their obscure aetiopathogenesis, and for years there was confusion and controversy regarding their nosography and taxonomy. Since the first WHO official classification,1 tremendous progress has been made.2 Novel entities have been discovered, requiring an update of the classification in 1995,3 and the aetiology of many forms has been clarified. The Working Group of Myocardial and Pericardial Disease of the European Society of Cardiology (ESC) recently published a position statement4 different from the 2006 American Heart Association (AHA) scientific statement.5 The scope of the present editorial is to deal with the nosographic impact of the advances made since 1995 and to comment on the ESC position statement which has been designed to provide a valid tool for routine clinical practice. The discovery of novel cardiomyopathies, namely arrhythmogenic right ventricular cardiomyopathy (ARVC), primary restrictive cardiomyopathy, and non-compacted myocardium, made a revision of the 1980 classification compulsory, and this led to many substantial, though often questionable, changes.3 Moreover, taking into consideration that the aetiology was becoming clearer and clearer, the definition was changed from ‘heart muscle disease of unknown aetiology’ into ‘myocardial disease associated with cardiac dysfunction’, the term dysfunction meaning both mechanical and electrical abnormality. In the new classification, ARVC6,7 and restrictive cardiomyopathy8 were added to the primary forms, whereas the non-compacted myocardium was left in the limbo of ‘unclassified cardiomyopathies’. The secondary forms, which in the classification of the 1980s were called specific heart muscle diseases, were given the name of ‘specific cardiomyopathies’, and within this group myocarditis was added. Unfortunately, the concept of specific cardiomyopathy was widened too much, so as to include chronic ischaemic, valvular, and hypertensive diseases. Although the 1995 classification made significant contributions … *Corresponding author. Tel: +39 049 8272283, Fax: +39 049 8272284, Email: gaetano.thiene{at}unipd.it

Understanding Diastolic Heart Failure With Preserved Ejection Fraction

Congestive heart failure (HF) is a frequent reason for hospital admission. Fifty percent of HF hospitalizations have normal ejection fraction (EF), 1 referred to as diastolic HF (DHF). In contrast, patients with systolic HF (SHF) have reduced EF. The DHF phenotype describes patients with signs and symptoms of HF, normal EF, normal left ventricular (LV) volume, hypertension with increased relative wall thickness, LV diastolic dysfunction, and predominantly elderly women. 1,2 Etiology of DHF Longstanding hypertension may result in significant myocardial hypertrophy, appearance of a smaller ventricular chamber, increased ventricular stiffness, and delayed relaxation. Increased ventricular stiffness requires increased pressure to maintain normal filling in the presence of normal or reduced chamber volume.3 Although DHF has not been studied as extensively as SHF, limited data obtained from patients hospitalized for DHF suggest that demographic characteristics, comorbidities, and pathology differ from those with SHF. Despite these differences, DHF is similar to SHF with regard to volume overload, reduced exercise capacity, impaired quality of life, and long-term mortality.1

Differentiation of constrictive pericarditis from restrictive cardiomyopathy using mitral annular velocity by tissue Doppler echocardiography

This study evaluated the diagnostic role of early diastolic mitral annular velocity (E′) by tissue Doppler echocardiography for differentiating constrictive pericarditis from restrictive cardiomyopathy (primary restrictive cardiomyopathy and cardiac amyloidosis). The study group consisted of 75 patients (53 men, 22 women; mean age 62 years, range 27 to 87). Of these, 23 patients had surgically confirmed constrictive pericarditis, 38 had biopsy-proved systemic amyloidosis and typical echocardiographic features of cardiac involvement, and 14 had primary restrictive cardiomyopathy. Standard mitral inflow characteristics were measured. Tissue Doppler echocardiography was used to measure E′ at the septal annulus. E′ was significantly higher in patients with constrictive pericarditis than in those with primary restrictive cardiomyopathy or cardiac amyloidosis (12.3 vs 5.1 cm/second, p <0.001). An E′ cut-off value ≥8 cm/second resulted in 95% sensitivity and 96% specificity for the diagnosis of constrictive pericarditis. There was no overlap of E′ between patients who had constrictive pericarditis and those who had cardiac amyloidosis. In a subgroup analysis of restrictive cardiomyopathy, E′ of patients who had cardiac amyloidosis was significantly lower than that of patients who had primary restrictive cardiomyopathy (4.6 vs 6.3 cm/second, p <0.001). Thus, E′ velocity can distinguish between constrictive pericarditis and restrictive cardiomyopathy with a specific cut-off value in patients with clinical and echocardiographic evidence of diastolic heart failure.

Clinical and molecular studies of a large family with desmin‐associated restrictive cardiomyopathy

Patients with restrictive cardiomyopathy (RC) have impaired diastolic function, but intact systolic function until later stages of the disease, ultimately leading to heart failure. Primary RC is often sporadic, but also may be inherited in an autosomal dominant fashion, particularly the idiopathic forms. Recently there has been great interest in inherited cardiomyopathy associated with myocyte desmin deposition ('desminopathies'). In some such families, desmin or alpha-B crystallin gene mutation is the underlying cause, and the desmin accumulation affects skeletal muscle as well, usually causing skeletal myopathy. We describe a large family with apparent autosomal dominant inheritance of desmin-associated RC spanning four generations, with the age of onset and severity/rate of progression being highly variable. This family is relatively unique in that there is no symptom-based evidence of skeletal muscle involvement, and the known desminopathy and cardiomyopathy genes/loci have been ruled out. These data support literature suggesting that desmin deposition may be associated with different underlying gene defects, and that a novel desminopathy gene is responsible for the condition in this family.

Morphologic spectrum of primary restrictive cardiomyopathy

A restrictive hemodynamic profile with left ventricular (LV) end-diastolic volume <100 ml/m 2 and LV enddiastolic pressure > 18 mm Hg, in the absence of endomyocardial, pericardial, and specific cardiomyopathy, is a peculiar feature of primary restrictive cardiomyopathy. From 1985 to 1994, 7 hearts of patients who met the above hemodynamic criteria and underwent endomyocardial biopsy because of heart failure, were studied through gross (5 cardiectomies and 2 autopsies), histologic, and electron microscopic investigations. Ages ranged from 9 to 48 years (mean age 29 ± 13). Four patients (57%) had a positive family history: 2 for hypertrophic and 2 for restrictive cardiomyopathy. Three patterns were identified in the 7 hearts: (1) pure restrictive form in 4 cases with mass/volume ratio 1.2 ± 0.5 g/ml, ejection fraction 58 ± 5%, LV end-diastolic volume 67.5 ± 12.6 ml/m 2, LV end-diastolic pressure 26.7 ± 3.5 mm Hg; (2) hypertrophic-restrictive form in 2 cases with mass/volume ratio 1.5 ± 0.07 g/ml, ejection fraction 62 ± 1%, LV end-diastolic volume 69 ± 10 ml/m 2, LV end-diastolic pressure 30 ± 7 mm Hg; and (3) mildly dilated restrictive form in 1 case with mass/volume ratio 0.9 g/ml, ejection fraction 25%, LV end-diastolic volume 98 ml/m 2, LV end-diastolic pressure 40 mm Hg. Histology and electron microscopy disclosed myocardial and myofibrillar disarray and endoperimysial interstitial fibrosis in each pattern. The familial forms suggest the presence of a genetic abnormality. Primary restrictive cardiomyopathy may present with or without hypertrophy and shares similar microscopic pictures with hypertrophic cardiomyopathy. The 2 entities may represent a different phenotypic expression of the same genetic disease.

Diagnostic findings and outcome in children with primary restrictive cardiomyopathy

SummaryRestrictive cardiomyopathy is a rare disease in children and adolescents. We have now encountered eight such cases in infants and children aged between nine months and 14 years. The reasons for admission to hospital were not very specific and included recurrent bronchitis, thoracic deformity, pathologic findings on routine electro-cardiography, or signs of cardiac failure. Despite two cases with atrial flutter, the characteristic electrocardiographic sign was a P-wave in lead II of about 0.6 to 1.5 m V. Echocardiographically, the leading feature was enlargement of the atriums, seen in cross-sectional and M-mode tracings. Diameters and functional parameters for the left ventricle, and the EF-slope of the mitral valve were normal. In four patients examined specifically for diis aspect, a typical E/A-ratio was found. Cardiac catheterization was performed in all patients. Left atrial or pulmonary capillary wedge pressures were all abnormal, and pulmonary arterial pressures ranged from 30 to 60 mm Hg. Calculated pulmonary resistances were 3 to 12 units per meter squared. End-diastolic left ventricular pressures were elevated, while comparable right-sided pressures were normal. Percutaneous endomyocardial biopsy was done in six patients and performed as an open biopsy in two. Only unspecified signs, such as myocytic hypertrophy or interstitial fibrosis, were found. At present, five of the children have died within two years of diagnosis. One boy has undergone cardiac transplantation success-fully. The two youngest children are still alive. As there is such a poor prognosis, and no alternative specific therapy is known, cardiac transplantation must be discussed with the family at an early stage, emphasizing its consequences.

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.

Radionuclide Detection of Abnormal Ventricular Filling Patterns in Rejecting Human Allografts

Parameters of systolic and diastolic function obtained from radionuclide ventriculography (RNV) were evaluated in nine cardiac allograft recipients. In 25 examinations, left end-diastolic volume (LEDV), cardiac output (CO), left ejection fraction (LEF), right ejection fraction (REF), heart rate (HR), peak filling rate (PFR), time to peak filling rate (TPFR), peak ejection rate (PER), and average filling rate for the first half of diastole (DFRH) were determined. Endomyocardial biopsy was obtained within 48 hours. Biopsies were divided into three treatment classes (0 = normal; 1 = rejection but not requiring supplemental therapy; and 2 = rejection requiring supplemental immunotherapy). Two independent variables of diastolic function proved to be significant (DFRH P less than 0.00001, and PFR P less than 0.002) predictors of the dependent variable class when regression analysis was applied to the data. Alterations in diastolic function associated with acute rejection are detectable on RNV and simulate changes anticipated in a primary restrictive cardiomyopathy.