De subitaneis mortibus. XXX. Observations on the pathophysiology of the long QT syndromes with special reference to the neuropathology of the heart.

Abstract

Eight patients (different families) with syncopal attacks and a long QT interval in the ECG died suddenly. Five heard normally and three were born deaf. At postmortem examination of all eight hearts the single consistent abnormality was focal neuritis and neural degeneration within the sinus node, A-V node, His bundle and ventricular myocardium. Although the etiology of this intracardiac neural disease is uncertain, a chronic viral infection or some noninfectious degenerative process are among the plausible causes discussed. If intracardiac neuritis and neural degeneration prove to be a prevalent finding among other victims dying from the long QT syndromes, further consideration should be given to whether there is any genuine hereditary component in the pathogenesis. Because of the asymmetrical and focal distribution of the cardioneural lesions, the response to present forms of medical or surgical treatment of the lung QT syndromes may vary from benefit to harm. Until more is known of the true etiology of the neural disease, treatment will probably remain empirical in nature and should be conducted with cautious clinical observation.

Crib death: further support for the concept of fatal cardiac electrical instability as the final common pathway

“…This is in contrast with other authors who considered instead the autopsy very important in every case of sudden death in infancy [67,88,94,107,108,114].…”

“…A notable example of multifocal apoptotic degeneration of the sinus node occurs in victims dying of the long-QT syndrome, a clinical entity characterized by sinus bradycardia [107,108]. Sudden unexpected death is one of the clinical characteristics of the long-QT syndrome and has often been documented to be mediated by lethal ventricular arrhythmias.…”

“…It is logical to anticipate that the normal occurrence of apoptotic cell death during postnatal morphogenesis of the sinus node will periodically distort or suppress normal sinus rhythm [105]. Moreover, in the long-QT syndrome apoptotic destruction involves not only the myocytes of the sinus node but also many local nerves and ganglia [107,108].…”

T-Cell–Mediated Inflammatory Activity in the Stellate Ganglia of Patients With Ion-Channel Disease and Severe Ventricular Arrhythmias

“…Normal ganglia also Intracardiac ganglionitis and its potential effect on arrhythmic risk have been previously described in LQTS subjects who died suddendly. [25][26][27] Ganglionitis and neuritis in the sinus node area were found also in liquid-protein-modified fast diet dieters who developed prolongation of the QT interval and ventricular arrhythmias after dieting. 28 In these studies, diffuse infiltration of mononuclear cells associated with neural degeneration was found at histological examination, lacking however of an immune characterization of the cellular composition and activity of the inflammatory population.…”

Ganglionitis and Genetic Cardiac Arrhythmias

“…Ganglionic protein damage might well result in a secondary autoimmune reaction with manifestations of ganglionitis. It is interesting that in 1978 Dr James et al 9 described postmortem intracardiac ganglionitis in 8…”