TP-fusion at peak exercise: A novel marker for the recognition of unsuspected long QT syndrome patients

Background and aims: The frequent occurrence of sudden death as the sentinel event in the Long QT Syndrome (LQTS) forces the search for still asymptomatic patients. We tested our hypothesis that complete fusion of the T and P waves (TP-fusion) at peak exercise might be a marker of likely LQTS. Methods: A maximal exercise stress test, off-therapy, was performed by healthy athletes and genotype-positive LQTS patients. TP-fusion had to be complete in all precordial leads except V1. Results: The study population (n=578) included 310 healthy athletes (all with QTc <430 ms) and 268 LQTS patients. To deal only with clear-cut phenotypes, 64 athletes and 70 patients with incomplete TP-fusion were excluded. TP-fusion was present in 2% of controls and in 22% (p<0.001) of the 198 LQTS patients. By limiting the analysis to subjects below age 25 (n=262), the prevalence of TP-fusion increased to 3% in healthy athletes and to 32% in LQTS (p<0.001). TP-fusion depends on the combination of QTc prolongation and fast heart rates; either alone is not sufficient. The appearance of TP-fusion predicted an 88% probability of being affected by LQTS. Importantly, of the 44 LQTS patients with TP-fusion, 24 (55%) had a borderline/normal baseline QTc (<460 ms). Conclusion: TP-fusion, a qualitative trait more easily assessable at peak exercise than QTc prolongation, especially outside referral centres, unmasks a high probability of LQTS, even in subjects with normal baseline QTc. Further clinical assessment and genetic screening allow life-saving prophylactic therapy.