Current management of inherited arrhythmia syndromes associated with the cardiac ryanodine receptor

Curr Opin Cardiol. 2023 Jul 1;38(4):390-395. doi: 10.1097/HCO.0000000000001051. Epub 2023 Mar 28.


Purpose of review: Gain-of-function variants in the gene encoding the cardiac ryanodine receptor ( RYR2 ) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). The exercise stress test (EST) has long been fundamental in diagnosis and management, but recent work has further explored its role. A new entity termed calcium release deficiency syndrome (CRDS) has been associated with loss-of-function RYR2 variants and a different arrhythmic phenotype.

Recent findings: Standard EST is not perfectly reproducible with regards to provocation of arrhythmia in CPVT. A newly described burst EST protocol may be more sensitive in this regard. Nadolol is the most effective beta blocker in CPVT, though arrhythmic events remain frequent and dual therapy with flecainide and/or left cardiac sympathetic denervation may add protection. A recent report renews debate regarding the use of implantable defibrillator therapy in CPVT. CRDS is characterized by later age of presentation, normal/near normal EST, and ventricular arrhythmia induced by a novel ventricular stimulation protocol.

Summary: Burst EST may aid in the diagnosis and management of CPVT. Nadolol is the preferred beta blocker in CPVT, and consideration should be given to early dual therapy. CRDS should be suspected in patients with arrhythmic events, rare RYR2 variants, and a phenotype inconsistent with CPVT.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-Antagonists
  • Flecainide / therapeutic use
  • Humans
  • Mutation
  • Nadolol
  • Ryanodine Receptor Calcium Release Channel* / genetics
  • Tachycardia, Ventricular* / diagnosis
  • Tachycardia, Ventricular* / genetics
  • Tachycardia, Ventricular* / therapy


  • Ryanodine Receptor Calcium Release Channel
  • Nadolol
  • Flecainide
  • Adrenergic beta-Antagonists