Importance: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite beta-blocker treatment. Further complicating... Show moreImportance: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite beta-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated. Objective: To investigate the long-term outcomes of patients with RYR2 CPVT treated with beta-blockers only and the cost to benefit ratio of ICD. Design, Settings, and Participants: 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 RYR2 variant with long-term clinical follow-up. Exposures: Treatment with selective and nonselective beta-blocker only and ICD implant when indicated. Main Outcome and Measures:The main outcome was the occurrence of the first LTAE while taking a beta-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia. Results: The cohort included 216 patients with RYR2 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 beta-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; P = .02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1; P = .001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8; P < .001) were associated with an increased LTAE risk during beta-blocker therapy only. The risk of LTAE among those taking selective beta-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3; P = .001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3; P = .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%]; P = .01). Conclusions and Relevance: In this cohort study, selective beta-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 beta-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT. Show less
Fortuni, F.; Butcher, S.C.; Kley, F. van der; Lustosa, R.P.; Karalis, I.; Weger, A. de; ... ; Marsan, N.A. 2021
Background: Left ventricular myocardial work (LVMW) is a novel method to assess left ventricular (LV) function using pressure-strain loops that takes into consideration LV afterload. The estimation... Show moreBackground: Left ventricular myocardial work (LVMW) is a novel method to assess left ventricular (LV) function using pressure-strain loops that takes into consideration LV afterload. The estimation of LV afterload in patients with severe aortic stenosis (AS) may be challenging, and no study so far has investigated LVMW in this setting. The aim of this study was to develop a method to calculate LVMW in patients with severe AS and to analyze its relationship with heart failure symptoms.Methods: Indices of LVMW were calculated in 120 patients with severe AS who underwent transcatheter aortic valve replacement and invasive LV and aortic pressure measurements. LV systolic pressure was also derived by adding the mean aortic valve gradient to the aortic systolic pressure. LV global longitudinal strain and echocardiography-derived LV systolic pressure were then incorporated to construct pressure-strain loops of the left ventricle.Results: An excellent correlation was observed between LVMW indices calculated using the invasive and echocardiography-derived LV systolic pressure. Patients in New York Heart Association functional class III or IV (n = 97 [73%]) had lower LV global longitudinal strain, LV global work index, LV global constructive work, and right ventricular free wall strain compared with those in New York Heart Association functional class I or II. In contrast to LV global longitudinal strain, LV global work index (odds ratio per 100 mm Hg% increase, 0.91; 95% CI, 0.85-0.98; P = .012) and LV global constructive work showed independent associations with New York Heart Association functional class III or IV heart failure symptoms.Conclusions: The calculation of echocardiography-based LVMW indices is feasible in patients with severe AS. In particular, LV global work index and global constructive work showed independent associations with heart failure symptoms and may provide additional information on myocardial remodeling and function in patients with severe AS. Show less
Priori, S.G.; Wilde, A.A.; Horie, M.; Cho, Y.; Behr, E.R.; Berul, C.; ... ; Tracy, C. 2013
