Advertisement

Dose response to nadolol in congenital long QT syndrome

      Background

      Beta-blocker therapy is the cornerstone of treatment for patients with long QT syndrome (LQTS). Few details on the dose to be used are available. As the response is variable between patients, we systematically evaluated the effect of treatment by performing an exercise test.

      Objective

      The purpose of this study was to explore dose response to nadolol on exercise test in LQTS patients in order to propose a more personalized therapeutic approach.

      Methods

      LQTS patients followed at the Reference Centre for Hereditary Arrhythmic Diseases of Nantes with at least 1 exercise test under nadolol were included retrospectively between 1993 and 2017. All patients underwent gradual cycle exercise tests. Doses adjusted to weight and response to treatment were recorded and evaluated by the percentage of age-predicted maximum heart rate reached on exercise test.

      Results

      Ninety-five patients were included in the study, and 337 stress tests under nadolol were analyzed. No correlation existed between dose and percentage of age-predicted maximum heart rate on exercise tests. Twenty-one patients were overresponders, mostly LQTS1, and 20 were underresponders, mainly LQTS2 (P = .0229). Forty-two patients had at least 3 stress tests under nadolol. We found a negative correlation between dose change and percentage of age-predicted maximum heart rate change (P <.0001). We then proposed a table to adapt dose according to exercise test response.

      Conclusion

      Our study demonstrated a major variability of dose response to nadolol in patients with LQTS, thus underlining the need for a tailored dosage for each patient. Intraindividual analysis showed a relatively constant dose–response relationship, allowing guided dose adaptation after the first exercise test.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Heart Rhythm
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bohnen M.S.
        • Peng G.
        • Robey S.H.
        • et al.
        Molecular pathophysiology of congenital long QT syndrome.
        Physiol Rev. 2017; 97: 89-134
        • Schwartz P.J.
        The congenital long QT syndromes from genotype to phenotype: clinical implications.
        J Intern Med. 2006; 259: 39-47
        • Napolitano C.
        • Bloise R.
        • Priori S.G.
        Long QT syndrome and short QT syndrome: how to make correct diagnosis and what about eligibility for sports activity.
        J Cardiovasc Med. 2006; 7: 250-256
        • Priori S.G.
        • Schwartz P.J.
        • Napolitano C.
        • et al.
        Risk stratification in the long-QT syndrome.
        N Engl J Med. 2003; 348: 1866-1874
        • Priori S.G.
        • Blomström-Lundqvist C.
        • Mazzanti A.
        • et al.
        • ESC Scientific Document Group
        ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC).
        Eur Heart J. 2015; 36: 2793-2867
        • Ward O.C.
        New familial cardiac syndrome in children.
        J Ir Med Assoc. 1964; 54: 103-106
        • Vincent G.M.
        • Schwartz P.J.
        • 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: 215-221
        • Moss A.J.
        • Zareba W.
        • Hall W.J.
        • et al.
        Effectiveness and limitations of betablocker therapy in congenital long QT syndrome.
        Circulation. 2000; 101: 616-623
        • Priori S.G.
        • Wilde A.A.
        • Horie M.
        • et al.
        EHRA executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
        Heart Rhythm. 2013; 10: 1932-1963
        • 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: 2092-2099
        • Toivonen L.
        More light on QT interval measurement.
        Heart. 2002; 87: 193-194
        • Goldenberg I.
        • Moss A.J.
        • Zareba W.
        QT interval: how to measure it and what is “normal”.
        J Cardiovasc Electrophysiol. 2006; 17: 333-336
        • Krahn A.D.
        • Gollob M.
        • Yee R.
        • et al.
        Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion.
        Circulation. 2005; 112: 2228-2234
        • Ackerman M.J.
        • Khositseth A.
        • Tester D.J.
        • Hejlik J.B.
        • Shen W.K.
        • Porter C.B.J.
        Epinephrine induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome.
        Mayo Clin Proc. 2002; 77: 413-421
        • Schwartz P.J.
        • Crotti L.
        QTc behavior during exercise and genetic testing for the long-QT syndrome.
        Circulation. 2011; 124: 2181-2184
        • Etienne P.
        • Huchet F.
        • Gaborit N.
        • et al.
        Mental stress test: a rapid, simple and efficient test to unmask long QT syndrome.
        Europace. 2018; 20: 2014-2020
        • Le Scouarnec S.
        • Karakachoff M.
        • Gourraud J.B.
        • et al.
        Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.
        Hum Mol Genet. 2015; 24: 2757-2763
        • Richards S.
        • Aziz N.
        • Bale S.
        • et al.
        • ACMG Laboratory Quality Assurance Committee
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
        Genet Med. 2015; 17: 405-424
        • Ackerman M.J.
        • Priori S.G.
        • Willems S.
        • et al.
        Expert consensus on the state of genetic testing for the channelopathies as cardiomyopathies.
        Europace. 2011; 13: 1077-1109
        • Priori S.G.
        • Napolitano C.
        • Schwartz P.J.
        • et al.
        Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers.
        JAMA. 2004; 292: 1341-1344
        • Abu-Zeitone A.
        • Peterson D.R.
        • Polonsky B.
        • McNitt S.
        • Moss A.J.
        Efficacy of different betablockers in the treatment of long QT syndrome.
        J Am Coll Cardiol. 2014; 64: 1352-1358