Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome

Federica Dagradi, Carla Spazzolini, Silvia Castelletti, Matteo Pedrazzini, Maria-Christina Kotta, Lia Crotti, Peter J Schwartz
Circulation 2020 October 19
Background: The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects that, over time, resulted as not affected. These individuals were all actively practicing sports, an observation which helped to design our study. Methods: We focused on subjects referred to our Center by Sports Medicine doctors with a suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening. Results: There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc 482±35 ms). Genetic testing was negative in 78 subjects but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, following detraining showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms, p<0.001, and their Schwartz score went from 3.0 to 0.06). They were considered not affected by congenital LQTS and are henceforth referred to as "Cases". Furthermore, among them, those who resume a similarly heavy physical training showed reappearance of the repolarization abnormalities. Conclusions: It is not uncommon to suspect LQTS among individuals actively practicing sports, based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG following detraining but the abnormalities tend to recur with resumption of training. These individuals are not affected by LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.

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