Verborgene intrakardiale Leitungsstörungen und deren spontaner Verlauf bei Patienten mit progressiver Muskeldystrophie

Abstract

In patients with progressive muscular dystrophy (PMD) invasive electrophysiologic studies can detect hidden intracardiac conduction disturbances. The aim of this study was a long-term follow-up of these patients. Twelve consecutive patients (9 m, 3 f, age 28 +/- 4 yrs) without cardiac symptoms and with normal echocardiographic findings were included in the study. They suffered from different stages of PMD type Erb (n = 4), Becker-Kiener (n = 4), Duchenne (n = 2) and Landouzy-Déjerine (n = 2). At the beginning of the study all patients underwent an invasive electrophysiologic study (EPS). The follow-up of 5.5 yrs included regular clinical visits, ECGs, and Holter recordings (every 3 months) as well as an echocardiography every 6 months. In 4 patients the EPS revealed a hidden interatrial conduction disturbance (AHRS-ACS 120 +/- 18 ms), and in 10 pts an infrahisian conduction disturbance was found (HV max. 156 +/- 4 ms). Conduction defects were seen independently from the type of PMD and the stage of the disease. During the follow-up the initially hidden interatrial conduction disturbance became evident in the surface ECG in 2 of 4 pts. One of them developed paroxysmal atrial fibrillation. Five of 10 pts with an initially hidden infrahisian conduction disturbance developed an AV block grade I-III and in one case additionally a bundle branch block. Four of these pts--whose PMD showed progression or who developed congestive cardiomyopathy--needed pacemaker implantation because of a first-degree AV block + bifascicular bundle branch block (n = 1), a Mobitz II second-degree AV block (n = 1) or a third-degree AV block (n = 2). None of the pts with normal findings at the EPS showed abnormal p-waves, an AV block, or an intraventricular conduction disturbance during the follow-up. We conclude that intracardiac conduction disturbances, especially infrahisian defects including high-degree AV blocks, are a common finding in pts with PMD. Therefore a regular cardiological screening including an ECG and a Holter recording is reasonable in these patients.

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

“…It is represented by a slowly progressing decline in diastolic function, systolic ejection fraction, and fractional shortening (Markham et al, 2006). Mechanical degeneration is associated with progressive cardiomyocyte (CM) wasting and spreading of fibrosis throughout the ventricular wall (Finsterer and Stöllberger, 2003;Panovský et al, 2019), which leads to intracardiac conduction disturbances, inducing atrial and life-threatening ventricular arrhythmias (Chenard et al, 1993;Himmrich et al, 2000). Gradual dilatation of the ventricle, thinning of the wall (Wagner et al, 2007), and consequent loss of contractility lead to repeated episodes of heart failure, which recently became the most frequent mortality cause in DMD patients worldwide (Finsterer and Stöllberger, 2003;Fayssoil et al, 2010).…”

Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

“…During teenage years, fibrosis affects also the cardiac muscle [5]. It is further exacerbated by intracardiac conduction disturbances, and it induces atrial and ventricular arrhythmias [6,7] leading to the development of dilated cardiomyopathy [8], and ultimately, to heart failure in DMD patients [5,9]. Disease progression and muscle degeneration leading to skeletal muscle wasting was recently also linked to satellite cell depletion [10,11].…”