Activation Delay After Premature Stimulation in Chronically Diseased Human Myocardium Relates to the Architecture of Interstitial Fibrosis

Abstract

Background-Progressive activation delay starting at long coupling intervals of premature stimuli has been shown to correlate with sudden cardiac death in patients with hypertrophic cardiomyopathy. The purpose of this study was to elucidate the mechanism of increased activation delay in chronically diseased myocardium. Methods and Results-High-resolution unipolar mapping (105, 208, or 247 recording sites with interelectrode distances of 0.8, 0.5, or 0.3 mm, respectively) of epicardial electrical activity was carried out during premature stimulation in 11 explanted human hearts. The hearts came from patients who underwent heart transplantation and were in the end stage of heart failure (coronary artery disease, 4; hypertrophic cardiomyopathy, 1; and dilated cardiomyopathy, 6). Eight hearts were Langendorff-perfused. Epicardial sheets were taken from the remaining hearts and studied in a tissue bath. Activation maps and conduction curves were constructed and correlated with histology. Conduction curves revealing prominent increase of activation delay were associated with zones of dense, patchy fibrosis with long fibrotic strands. Dense, diffuse fibrosis with short fibrotic strands only marginally affected conduction curves. The course of conduction curves in patchy fibrotic areas greatly depended on the direction of propagation relative to fiber direction. Conclusions-The study demonstrates that in chronically diseased human myocardium, nonuniform anisotropic characteristics imposed by long fibrotic strands cause a progressive increase of activation delay, starting at long coupling intervals of premature stimuli. The increase strongly depends on the direction of the wave front with respect to fiber direction and the architecture of fibrosis.

Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function

“…27 Kawara et al reported the correlation of conduction delay with a fibrotic tissue pattern in chronic diseased myocardium, including HCM, particularly in areas of patchy fibrosis. 28 In this study, QRS duration on standard 12-lead ECG was associated with lethal arrhythmic events only in the univariate analysis (Table 3); however, the severity of fibrosis in the tissue samples was weakly associated with a longer delayed potential (LAS40) (Figure S2). These findings suggest that the increased fibrosis in HCM associated with longer QRS duration and positive LP represented by prolonged delayed potential detected by SAECG indicates an abnormal conduction delay and may contribute at least in part to the increased incidence of lethal ventricular arrhythmias or SCD.…”

Enrichment of neonatal rat cardiomyocytes in primary culture facilitates long-term maintenance of contractility in vitro

“…Previous studies have shown that excessive connective tissue and fibroblasts can act as a current sink for connected CMs, obstruct electrical excitation, and contribute to discontinuous conduction and arrhythmia (11,18,34). Similarly, a recent study also reported that cocultures of CMs and myofibroblasts disrupted electrical coupling and field potential propagation between CMs (36).…”

Comparison of amiodarone and propafenone for maintenance of stable sinus rhythm after bipolar radiofrequency ablation combined with a mitral valve procedure in patients with mitral valve disease and persistent atrial fibrillation

“…It is reasonable to expect that cellular, structural morphological, and parallel electrophysiological changes in the atrial tissue play a more prominent role in the progressive enlargement and hypertrophy of the atria. [10,11] Restoration of sinus rhythm by ablation leads to a greater quality of life (QoL), especially when compared with patients who have persistent AF that experience a sustained abnormal heartbeat and undergo mitral valve surgery. [12] Moreover, Pappone et al [13] reported reduced mortality and morbidity and an improved QoL in patients who underwent circumferential pulmonary vein ablation for AF versus those treated with medical therapy alone.…”