Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers
Authors: Andrea Mazzanti, Deni Kukavica, Alessandro Trancuccio, Mirella Memmi, Raffaella Bloise, Patrick Gambelli, Maira Marino, Martín Ortíz-Genga, Massimo Morini, Nicola Monteforte, Umberto Giordano, Roberto Keegan, Luca Tomasi, Aristides Anastasakis, Andrew M. Davis, Wataru Shimizu, Nico A. Blom, Demetrio Julián Santiago, Carlo Napolitano, Lorenzo Monserrat, Silvia G. Priori
Journal: JAMA Cardiology (2022)

<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.