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Long QT syndrome type 1 and 2 patients respond differently to arrhythmic triggers: The TriQarr in vivo study

Published:August 31, 2020DOI:https://doi.org/10.1016/j.hrthm.2020.08.017

      Background

      In patients with long QT syndrome (LQTS), swimming and loud noises have been identified as genotype-specific arrhythmic triggers in LQTS type 1 (LQTS1) and LQTS type 2 (LQTS2), respectively.

      Objective

      The purpose of this study was to compare LQTS group responses to arrhythmic triggers.

      Methods

      LQTS1 and LQTS2 patients were included. Before and after beta-blocker intake, electrocardiograms were recorded as participants (1) were exposed to a loud noise of ∼100 dB; and (2) had their face immersed into cold water.

      Results

      Twenty-three patients (9 LQTS1, 14 LQTS2) participated. In response to noise, LQTS groups showed similarly increased heart rate, but LQTS2 patients had corrected QT interval (Fridericia formula) (QTcF) prolonged significantly more than LQTS1 patients (37 ± 8 ms vs 15 ± 6 ms; P = .02). After intake of beta-blocker, QTcF prolongation in LQTS2 patients was significantly blunted and similar to that of LQTS1 patients (P = .90). In response to simulated diving, LQTS groups experienced a heart rate drop of ∼28 bpm, which shortened QTcF similarly in both groups. After intake of beta-blockers, heart rate dropped to 28 ± 2 bpm in LQTS1 patients and 20 ± 3 bpm in LQTS2, resulting in a slower heart rate in LQTS1 compared with LQTS2 (P = .01). In response, QTcF shortened similarly in LQTS1 and LQTS2 patients (57 ± 9 ms vs 36 ± 7 ms; P = .10).

      Conclusion

      When exposed to noise, LQTS2 patients had QTc prolonged significantly more than did LQTS1 patients. Importantly, beta-blockers reduced noise-induced QTc prolongation in LQTS2 patients, thus demonstrating the protective effect of beta-blockers. In response to simulated diving, LQTS groups responded similarly, but a slower heart rate was observed in LQTS1 patients during simulated diving after beta-blocker intake.

      Keywords

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      References

        • Priori S.G.
        • Wilde A.A.
        • Horie M.
        • et al.
        Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
        Europace. 2013; 15: 1389-1406
        • Napolitano C.
        • Priori S.G.
        • Schwartz P.J.
        • et al.
        Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.
        J Am Med Assoc. 2005; 294: 2975-2980
        • Schwartz P.J.
        • Priori S.G.
        • Spazzolini C.
        • et al.
        Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias.
        Circulation. 2001; 103: 89-95
        • Wilde A.A.M.
        • Jongbloed R.J.E.
        • Doevendans P.A.
        • et al.
        Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1).
        J Am Coll Cardiol. 1999; 33: 327-332
        • Moss A.J.
        • Robinson J.L.
        • Gessman L.
        • et al.
        Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome.
        Am J Cardiol. 1999; 84: 876-879
        • Ackerman M.J.
        • Tester D.J.
        • Porter B.J.
        Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome.
        Mayo Clin Proc. 1999; 74: 1088-1094
        • Marstrand P.
        • Theilade J.
        • Andersson C.
        • et al.
        Long QT syndrome is associated with an increased burden of diabetes, psychiatric and neurological comorbidities: a nationwide cohort study.
        Open Heart. 2019; 6e001161
        • Shattock M.J.
        • Tipton M.J.
        “Autonomic conflict”: a different way to die during cold water immersion?.
        J Physiol. 2012; 590: 3219-3230
        • Ahn J.
        • Kim H.J.
        • Choi J. Il
        • et al.
        Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: a meta-analysis.
        PLoS One. 2017; 12e0185680
        • Postema P.G.
        • De Jong J.S.S.G.
        • Van der Bilt I.A.C.
        • Wilde A.A.M.
        Accurate electrocardiographic assessment of the QT interval: teach the tangent.
        Heart Rhythm. 2008; 5: 1015-1018
        • Kim J.A.
        • Lopes C.M.
        • Moss A.J.
        • et al.
        Trigger-specific risk factors and response to therapy in long QT syndrome type 2.
        Heart Rhythm. 2010; 7: 1797-1805
        • Viskin S.
        • Postema P.G.
        • Bhuiyan Z.A.
        • et al.
        The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome.
        J Am Coll Cardiol. 2010; 55: 1955-1961
        • Bennett M.T.
        • Gula L.J.
        • Klein G.J.
        • et al.
        Effect of beta-blockers on QT dynamics in the long QT syndrome: measuring the benefit.
        Europace. 2014; 16: 1847-1851
        • Waddell-Smith K.E.
        • Li J.
        • Smith W.
        • Crawford J.
        • Skinner J.R.
        β-Blocker adherence in familial long QT syndrome.
        Circ Arrhythmia Electrophysiol. 2016; 9e003591
        • Shamsuzzaman A.
        • Ackerman M.J.
        • Kuniyoshi F.S.
        • et al.
        Sympathetic nerve activity and simulated diving in healthy humans.
        Auton Neurosci Basic Clin. 2014; 181: 74-78
        • Liu J.
        • Laurita K.R.
        The mechanism of pause-induced torsade de pointes in long QT syndrome.
        J Cardiovasc Electrophysiol. 2005; 16: 981-987
        • Goldenberg I.
        • Thottathil P.
        • Lopes C.M.
        • et al.
        Trigger-specific ion-channel mechanisms, risk factors, and response to therapy in type 1 long QT syndrome.
        Heart Rhythm. 2012; 9: 49-56
        • Viskin S.
        • Rosovski U.
        • Sands A.J.
        • et al.
        Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one.
        Heart Rhythm. 2005; 2: 569-574