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Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients
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  1. A V Postma1,2,
  2. I Denjoy2,3,
  3. J Kamblock4,
  4. M Alders5,
  5. J-M Lupoglazoff2,
  6. G Vaksmann6,
  7. L Dubosq-Bidot7,
  8. P Sebillon8,
  9. M M A M Mannens5,
  10. P Guicheney2,
  11. A A M Wilde1
  1. 1Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
  2. 2INSERM U582, Institut de Myologie, IFR 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  3. 3Service de Cardiologie, Hôpital Lariboisière, Paris, France
  4. 4Centre de Cardiologie du Taaone, Tahiti, French Polynesia
  5. 5Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
  6. 6Service de Cardiologie Pediatrique, Hopital Cardiologique, Lille, France
  7. 7INSERM U621, IFR 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  8. 8Laboratoire de génétique et insuffisance cardiaque, Association Claude Bernard, IFR 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  1. Correspondence to:
 Alex V Postma
 Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, PO Box 22700 1100 DE, Amsterdam, The Netherlands; a.v.postmaamc.uva.nl

Abstract

Background: The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands.

Methods and results: We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On β blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2–37) years.

Conclusion: CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with β blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of β blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies.

  • CASQ2, calsequestrin 2
  • CCD, central core disease
  • CPVT, catecholaminergic polymorphic ventricular tachycardia
  • ECG, electrocardiogram
  • ICD, implantable cardioverter defibrillator
  • PVC, premature ventricular contraction
  • RYR2, ryanodine type 2 receptor
  • SA, sino-atrial
  • SR, sarcoplasmic reticulum
  • arrhythmia
  • genetics
  • ryanodine receptor
  • syncope
  • tachycardia
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Footnotes

  • This work was supported by grants from the Fondation Leducq, the Interuniversitair Cardiologisch Instituut Nederland (ICIN) project 27, and NWO grant 902.16.193.

  • Competing interests: none declared

  • Ethics approval: All individuals gave informed consent to the clinical and genetic study, which was approved by the internal ethics committee.

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