Long reflections on the QT interval: the sixth annual Gordon K. Moe Lecture.

This review of accumulated knowledge about the long QT syndromes begins with an iteration of the original papers and then proceeds to a broader historic reflection that includes my personal work as well as many studies by others. Next come reflections upon the current status of knowledge on the subject, combined with comments about remaining challenges and questions grouped as follows: (1) morphologic abnormalities of the cardiac conduction system and their pathophysiologic significance in the long QT syndromes; (2) cardioneuropathy in the pathogenesis of long QT syndromes; (3) variability of QT prolongation, including consideration of peripheral and central dysautonomic conditions with certain diagnostic and therapeutic implications; (4) some caveats about the popular use of left cervical sympathectomy to treat symptomatic individuals with long QT syndrome, emphasizing hazards for future electrical instability of the heart; (5) consideration of genetic influences in the long QT syndromes, a field holding great promise as well as fraught with many puzzling dilemmas; and (6) apoptosis and the pathogenesis of the long QT syndromes, based upon personal observations previously made with electron microscopic studies of the sinus node and now including new immunohistochemical evidence expanding the relevance of this novel view-point. These intentionally provocative presentations are made to stimulate physicians and other scientists to consider these several different perspectives in planning future studies aimed at better understanding of one of the most challenging medical entities facing cardiology today.