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Crotti, L. ; Spazzolini, C.* ; Porretta, A.P.* ; Dagradi, F.* ; Taravelli, E.* ; Petracci, B.* ; Vicentini, A.* ; Pedrazzini, M.* ; La Rovere, M.T.* ; Vanoli, E.* ; Goosen, A.* ; Heradien, M.* ; George, A.L.* ; Brink, P.A.* ; Schwartz, P.J.*

Vagal reflexes following an exercise stress test: A simple clinical tool for gene-specific risk stratification in the long QT syndrome.

J. Am. Coll. Cardiol. 60, 2515-2524 (2012)

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Objectives The study assessed whether heart rate (HR) reduction following an exercise stress test (ExStrT), an easily quantifiable marker of vagal reflexes, might identify high-and low-risk long QT syndrome (LQTS) type 1 (LQT1) patients. Background Identification of LQTS patients more likely to be symptomatic remains elusive. We have previously shown that depressed baroreflex sensitivity, an established marker of reduced vagal reflexes, predicts low probability of symptoms among LQT1. Methods We studied 169 LQTS genotype-positive patients < 50 years of age who performed an ExStrT with the same protocol, on and off beta-blockers including 47 South African LQT1 patients all harboring the KCNQ1-A341V mutation and 122 Italian LQTS patients with impaired (I-Ks-, 66 LQT1) or normal (I-Ks +/-, 50 LQT2 and 6 LQT3) I-Ks current. Results Despite similar maximal HR and workload, by the first minute after cessation of exercise the symptomatic patients in both IKs-groups had a greater HR reduction compared with the asymptomatic (19 +/- 7 beats/min vs. 13 +/- 5 beats/min and 27 +/- 10 beats/min vs. 20 +/- 8 beats/min, both p = 0.009). By contrast, there was no difference between the I-Ks +/- symptomatic and asymptomatic patients (23 +/- 9 beats/min vs. 26 +/- 9 beats/min, p = 0.47). LQT1 patients in the upper tertile for HR reduction had a higher risk of being symptomatic (odds ratio: 3.28, 95% confidence interval: 1.3 to 8.3, p = 0.012). Conclusions HR reduction following exercise identifies LQT1 patients at high or low arrhythmic risk, independently of beta-blocker therapy, and contributes to risk stratification. Intense exercise training, which potentiates vagal reflexes, should probably be avoided by LQT1 patients.

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