Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.

Abstract

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage IL disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.Circulation 74, No. 1, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] 1986

Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association

“…DCM usually presents late in the course but is out of proportion to the degree of conduction system disease. 489 The echocardiographic and histological findings in both subgroups are classic for DCM, although the conduction system may be fibrotic in patients with conduction system disease. Furthermore, there may be other forms of DCM associated with arrhythmia.…”

“…474,475 Patients with this form of the disease present as classic "pure" DCM or DCM associated with conduction system disease. 489 Patients usually present in the third decade of life with mild conduction system disease that can progress to complete heart block over decades. DCM usually presents late in the course but is out of proportion to the degree of conduction system disease.…”

Common Variant in AMPD1 Gene Predicts Improved Clinical Outcome in Patients With Heart Failure

“…A lthough family studies have suggested that there may be a genetic basis for inherited cardiomyopathy, [1][2][3][4][5] few studies have attempted to define genetic determinants of disease duration in the general population of patients with heart failure.…”

The Problem of Ventricular Dysrhythmias and Sudden Death Mortality in Heart Failure: The Impact of Current Therapy

“…The major predictors of early cardiovascular death in heart failure are primarily related to ventricular function, clinical status, and ventricular dysrhythmias (table 1) [1, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44]. Various parameters of each of these major categories have been reported to represent the best index of survival (for example, left ventricular stroke work, protodiastolic gallop, frequency of ventricular ectopic beats; see table 1).…”