Haugaa, Kristina H.

Abstract Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for malignant ventricular arrhythmias during exercise and emotions which may lead to sudden cardiac death. Beta-blockers (BB) are the mainstay of therapy in patients with CPVT, but studies comparing the efficacy of different types of BB are scarce. Our objective was to determine the efficacy of different types of BB in reducing the ventricular arrhythmia (VA) severity on exercise stress test (EST) in patients with CPVT. Data was derived from the International CPVT Registry, a large retrospective cohort study. We included patients who had an EST before (pre-EST) and after start of BB (post-EST). We divided the cohort into five groups based on the first prescribed BB and compared pre-EST and post-EST. We included 428 patients (median age 18.5 [11.7–39.6] years, 240 (56.%) female), 155 (36.2%) probands) of whom 38 (8.9%) used atenolol, 131 (30.6%) bisoprolol, 82 (19.2%) metoprolol, 124 (29.0%) nadolol and 53 (12.4%) propranolol. Sex and history of aborted cardiac arrest were similar in all groups. The age at start of BB differed (p<0,001): patients using bisoprolol were oldest (35.0 [15.7–35.3]) while patients using propranolol were youngest (12.3 [8.8–24.9]). Median daily BB dose in mg/kg was: 1.0 [0.8–2.3] for atenolol, 0.06 [0.05–0.10] for bisoprolol, 0.9 [0.6–1.5] for metoprolol, 1.1 [0.9–1.6] for nadolol and 1.5 [1.1–2.8] for propranolol. Resting heart rate on pre-EST and post-EST was similar in all groups. Patients using metoprolol had a significantly higher maximum heart rate post-EST compared to nadolol and propranolol (161±18 vs 136±19 and 130±22 bpm, p=0,002 and p=0,001, respectively). The VA severity decreased significantly after BB (147 (37.9%) (non-sustained) ventricular tachycardia ((NS)VT) and 120 (30.9%) no or isolated ventricular premature beat (iVPB) pre-EST vs 46 (11.4%) (NS)VT and 184 (45.7%) iVPB post-EST, p<0,001). Examining the different groups, the VA severity decreased significantly after BB in all but atenolol (13 (40.6%) (NS)VT and 8 (25.0%) iVPB pre-EST vs 9 (25.0%) (NS)VT and 15 (41.7%) iVPB post-EST, p=0,103). Based on these results we conclude that all beta-blockers except atenolol are effective in reducing the VA severity on EST in patients with CPVT. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): E-Rare Joint Transnational Call for Proposals 2015 “Improving Diagnosis and Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: Integrating Clinical and Basic Science”

Background: Risk stratification in catecholaminergic polymorphic ventricular tachycardia remains ill defined. Heart rate recovery (HRR) immediately after exercise is regulated by autonomic reflexes, particularly vagal tone, and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. Our objective was to evaluate whether HRR after maximal exercise on the exercise stress test (EST) is associated with symptoms and ventricular arrhythmias. Methods: In this retrospective observational study, we included patients ≤65 years of age with an EST without antiarrhythmic drugs who attained at least 80% of their age- and sex-predicted maximal HR. HRR in the recovery phase was calculated as the difference in heart rate (HR) at maximal exercise and at 1 minute in the recovery phase (ΔHRR1′). Results: We included 187 patients (median age, 36 years; 68 [36%] symptomatic before diagnosis). Pre-EST HR and maximal HR were equal among symptomatic and asymptomatic patients. Patients who were symptomatic before diagnosis had a greater ΔHRR1′ after maximal exercise (43 [interquartile range, 25–58] versus 25 [interquartile range, 19–34] beats/min; P <0.001). Corrected for age, sex, and relatedness, patients in the upper tertile for ΔHRR1′ had an odds ratio of 3.4 (95% CI, 1.6–7.4) of being symptomatic before diagnosis ( P <0.001). In addition, ΔHRR1′ was higher in patients with complex ventricular arrhythmias at EST off antiarrhythmic drugs (33 [interquartile range, 22–48] versus 27 [interquartile range, 20–36] beats/min; P =0.01). After diagnosis, patients with a ΔHRR1′ in the upper tertile of its distribution had significantly more arrhythmic events as compared with patients in the other tertiles ( P =0.045). Conclusions: Catecholaminergic polymorphic ventricular tachycardia patients with a larger HRR following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during the first EST off antiarrhythmic drug.

Abstract Aims In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), implantable cardioverter-defibrillator (ICD) shocks are sometimes ineffective and may even trigger fatal electrical storms. We assessed the efficacy and complications of ICDs placed in patients with CPVT who presented with a sentinel event of sudden cardiac arrest (SCA) while undiagnosed and therefore untreated. Methods and results We analysed 136 patients who presented with SCA and in whom CPVT was diagnosed subsequently, leading to the initiation of guideline-directed therapy, including β-blockers, flecainide, and/or left cardiac sympathetic denervation. An ICD was implanted in 79 patients (58.1%). The primary outcome of the study was sudden cardiac death (SCD). The secondary outcomes were composite outcomes of SCD, SCA, appropriate ICD shocks, and syncope. After a median follow-up of 4.8 years, SCD had occurred in three patients (3.8%) with an ICD and none of the patients without an ICD (P = 0.1). SCD, SCA, or appropriate ICD shocks occurred in 37 patients (46.8%) with an ICD and 9 patients (15.8%) without an ICD (P &lt; 0.0001). Inappropriate ICD shocks occurred in 19 patients (24.7%) and other device-related complications in 22 patients (28.9%). Conclusion In previously undiagnosed patients with CPVT who presented with SCA, an ICD was not associated with improved survival. Instead, the ICD was associated with both a high rate of appropriate ICD shocks and inappropriate ICD shocks along with other device-related complications. Strict adherence to guideline-directed therapy without an ICD may provide adequate protection in these patients without all the potential disadvantages of an ICD.

Abstract This joint position paper illustrates the role and the correct use of echocardiography, radionuclide imaging with 18F-fluorodeoxyglucose positron emission tomography, radionuclide myocardial perfusion imaging and cardiovascular magnetic resonance imaging for the evaluation and management of patients with known or suspected cardiac sarcoidosis. This position paper will aid in standardizing imaging for cardiac sarcoidosis and may facilitate clinical trials and pooling of multi-centre data on cardiac sarcoidosis. Proposed flow charts for the work up and management of cardiac sarcoidosis are included.