Effect of moderate potassium-elevating treatment in long QT syndrome: the TriQarr Potassium Study

Peter Marstrand, Kasim Almatlouh, Jørgen K Kanters, Claus Graff, Alex Hørby Christensen, Henning Bundgaard, Juliane Theilade, Peter Marstrand, Kasim Almatlouh, Jørgen K Kanters, Claus Graff, Alex Hørby Christensen, Henning Bundgaard, Juliane Theilade

Abstract

Background: In long QT syndrome (LQTS), beta blockers prevent arrhythmias. As a supplement, means to increase potassium has been suggested. We set to investigate the effect of moderate potassium elevation on cardiac repolarisation.

Methods: Patients with LQTS with a disease-causing KCNQ1 or KCNH2 variant were included. In addition to usual beta-blocker treatment, patients were prescribed (1) 50 mg spironolactone (low dose) or (2) 100 mg spironolactone and 3 g potassium chloride per day (high dose+). Electrocardiographic measures were obtained at baseline and after 7 days of treatment.

Results: Twenty patients were enrolled (10 low dose and 10 high dose+). One patient was excluded due to severe influenza-like symptoms, and 5 of 19 patients completing the study had mild side effects. Plasma potassium in low dose did not increase in response to treatment (4.26±0.22 to 4.05±0.19 mmol/L, p=0.07). Also, no change was observed in resting QTcF (QT interval corrected using Fridericia's formula) before versus after treatment (478±7 vs 479±7 ms, p=0.9). In high dose+, potassium increased significantly from 4.08±0.29 to 4.48±0.54 mmol/L (p=0.001). However, no difference in QTcF was observed comparing before (472±8 ms) versus after (469±8 ms) (p=0.66) high dose+ treatment. No patients developed hyperkalaemia.

Conclusion: In patients with LQTS, high dose+ treatment increased plasma potassium by 0.4 mmol/L without cases of hyperkalaemia. However, the potassium increase did not shorten the QT interval and several patients had side effects. Considering the QT interval as a proxy for arrhythmic risk, our data do not support that potassium-elevating treatment has a role as antiarrhythmic prophylaxis in patients with LQTS with normal-range potassium levels.

Trial registration number: NCT03291145.

Keywords: arrhythmias; cardiac; clinical; electrophysiology; genetics; pharmacology; ventricular fibrillation.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Mean (A) and individual (B) changes of plasma potassium in response to potassium-elevating treatment. Adding 50 mg spironolactone to the usual beta-blocker treatment did not change plasma potassium levels, but 100 mg spironolactone and potassium chloride significantly increased plasma potassium from 4.08 to 4.48 mmol/L.
Figure 2
Figure 2
ECG examples of a patient treated with 100 mg spironolactone and 3 g potassium chloride in addition to usual beta-blocker treatment. QT intervals are shown at rest and at maximum heart rate during standing. (A) ECG recording in usual beta-blocker treatment and (B) ECG after 1 week of potassium-elevating treatment.
Figure 3
Figure 3
Effect of potassium-elevating treatment in different doses on QTcF interval at rest and at maximum heart rate during brisk standing. (A) The QTcF response to brisk standing is shown on the left, before versus after treatment with 50 mg spironolactone. (B) The QTcF response to brisk standing is shown on the right, before versus after treatment with 100 mg spironolactone+3 g potassium chloride.

References

    1. Moss AJ, Zareba W, Hall WJ, et al. . Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000;101:616–23. 10.1161/01.CIR.101.6.616
    1. Priori SG, Wilde AA, 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;15:1389–406. 10.1093/europace/eut272
    1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. . 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American heart association Task force on clinical practice guidelines and the heart rhythm Society. Circulation 2018;138:e272–391. 10.1161/CIR.0000000000000549
    1. Etheridge SP, Compton SJ, Tristani-Firouzi M, et al. . A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with hERG mutations. J Am Coll Cardiol 2003;42:1777–82. 10.1016/j.jacc.2003.07.006
    1. Compton SJ, Lux RL, Ramsey MR, et al. . Genetically defined therapy of inherited long-QT syndrome. correction of abnormal repolarization by potassium. Circulation 1996;94:1018–22. 10.1161/01.cir.94.5.1018
    1. Goldenberg I, Moss AJ. Reply. J Am Coll Cardiol 2008;52:1605–6. 10.1016/j.jacc.2008.07.054
    1. Marstrand P, Almatlouh K, Kanters JK, et al. . Long QT syndrome type 1 and 2 patients respond differently to arrhythmic triggers: The TriQarr in vivo study. Heart Rhythm 2021;18:241–9. 10.1016/j.hrthm.2020.08.017
    1. Viskin S, Postema PG, Bhuiyan ZA, 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;55:1955–61. 10.1016/j.jacc.2009.12.015
    1. Postema PG, De Jong JSSG, Van der Bilt IAC, et al. . Accurate electrocardiographic assessment of the QT interval: teach the tangent. Heart Rhythm 2008;5:1015–8. 10.1016/j.hrthm.2008.03.037
    1. Graff C, Andersen MP, Xue JQ, et al. . Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology. Drug Saf 2009;32:599–611. 10.2165/00002018-200932070-00006
    1. R Development Core Team R . R: A Language and Environment for Statistical Computing, version 3.6.1. R Found Stat Comput [Internet]. 1, 2019: 409.
    1. Nijsten MW, de Smet BJ, Dofferhoff AS. Pseudohyperkalemia and platelet counts. N Engl J Med 1991;325:1107. 10.1056/NEJM199110103251515
    1. Sanguinetti MC, Jiang C, Curran ME, et al. . A mechanistic link between an inherited and an acquired cardiac arrhythmia: hERG encodes the IKr potassium channel. Cell 1995;81:299–307. 10.1016/0092-8674(95)90340-2
    1. Pezhouman A, Singh N, Song Z, et al. . Molecular basis of Hypokalemia-Induced ventricular fibrillation. Circulation 2015;132:1528–37. 10.1161/CIRCULATIONAHA.115.016217
    1. Beldhuis IE, Myhre PL, Claggett B, et al. . Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease. JACC Heart Fail 2019;7:25–32. 10.1016/j.jchf.2018.10.017
    1. Waddell-Smith KE, Li J, Smith W, et al. . β-Blocker Adherence in Familial Long QT Syndrome. Circulation 2016;9. 10.1161/CIRCEP.115.003591
    1. Vincent GM, Schwartz PJ, Denjoy I, et al. . High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment "failures". Circulation 2009;119:215–21. 10.1161/CIRCULATIONAHA.108.772533
    1. Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:1414–9. 10.1056/NEJM198312083092303
    1. Abu-Zeitone A, Peterson DR, Polonsky B, et al. . Efficacy of different beta-blockers in the treatment of long QT syndrome. J Am Coll Cardiol 2014;64:1352–8. 10.1016/j.jacc.2014.05.068
    1. Chockalingam P, Crotti L, Girardengo G, et al. . Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol 2012;60:2092–9. 10.1016/j.jacc.2012.07.046
    1. Mazzanti A, Maragna R, Vacanti G, et al. . Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome. J Am Coll Cardiol 2018;71:1663–71. 10.1016/j.jacc.2018.01.078

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe