Calcium

Cohort

Tachycardia

Cardiology

Ryanodine receptor

Catecholaminergic polymorphic ventricular tachycardia

Ryanodine receptor 2

Ventricular tachycardia

Internal medicine

Implantable cardioverter-defibrillator

Prospective cohort study

Confidence interval

Hazard ratio

Sudden cardiac death

Medicine

JAMA Cardiology

<h3>Importance</h3> Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite β-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated. <h3>Objective</h3> To investigate the long-term outcomes of patients with<i>RYR2</i>CPVT treated with β-blockers only and the cost to benefit ratio of ICD. <h3>Design, Settings, and Participants</h3> This prospective cohort study conducted from January 1988 to October 2020 with a mean (SD) follow-up of 9.4 (7.5) years included patients who were referred to the Molecular Cardiology Clinics of ICS Maugeri Hospital, Pavia, Italy. Participants included consecutive patients with CPVT who were carriers of a pathogenic or likely pathogenic<i>RYR2</i>variant with long-term clinical follow-up. <h3>Exposures</h3> Treatment with selective and nonselective β-blocker only and ICD implant when indicated. <h3>Main Outcome and Measures</h3> The main outcome was the occurrence of the first LTAE while taking a β-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia. <h3>Results</h3> The cohort included 216 patients with<i>RYR2 </i>CPVT (121 of 216 female [55%], median [IQR] age 14, [9-30] years). During a mean (SD) follow-up of 9.4 (7.5) years taking β-blockers only, 28 of 216 patients (13%) experienced an LTAE (annual rate, 1.9%; 95% CI, 1.3-2.7). In multivariable analysis, experiencing either an LTAE (hazard ratio [HR], 3.3; 95% CI, 1.2-8.9;<i>P</i> = .02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1;<i>P</i> = .001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8;<i>P</i> &lt; .001) were associated with an increased LTAE risk during β-blocker therapy only. The risk of LTAE among those taking selective β-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3;<i>P</i> = .001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3;<i>P</i> = .44). An ICD was implanted in 79 of 216 patients (37%) who were followed up for a mean (SD) of 8.6 (6.3) years. At the occurrence of LTAE, ICD carriers were more likely to survive (18 of 18 [100%]) than non-ICD carriers (6 of 10 [60%];<i>P</i> = .01). <h3>Conclusions and Relevance</h3> In this cohort study, selective β-blockers were associated with a higher risk of LTAE as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT.

Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers