Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Androgenic effects on ventricular repolarization: A translational study from the international pharmacovigilance database to iPSC-cardiomyocytes

International audienceBackground: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking.Methods: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone.Results: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; P<0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25μM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, P<0.001) and 1062.3±28.9ms (chronic; P<0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells.Conclusion: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs.Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138

Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers

Cardiolog

Extracorporeal Membrane Oxygenation to Support Life-Threatening Drug-Refractory Electrical Storm

Objectives: Despite rapid implementation of anti-arrhythmic treatment and sedation and controlling the triggering event, rare patients develop treatment-refractory electrical storm and their hemodynamic instability prevents emergency catheter ablation. In that context, venoarterial extracorporeal membrane oxygenation could rapidly restore hemodynamics and tissue perfusion and reduce myocardial oxygen consumption, until adequate anti-arrhythmic drug levels are reached to safely perform catheter ablation. Design: Retrospective, multicenter study over an 8-year period. Setting: Two French tertiary care centers. Patients: Eighty-three consecutive adults with venoarterial extracorporeal membrane oxygenation-supported treatment-refractory electrical storm (median [interquartile range] age, 55 yr [48-63 yr]). Measurements and Main Results: Fifty-nine percent of these patients had acute ischemic cardiomyopathy and 66% underwent cardiopulmonary resuscitation prior to venoarterial extracorporeal membrane oxygenation initiation, with 18% cannulated during it. Fifty patients (60%) had ventricular tachycardia and/or ventricular fibrillation alternating with short periods of sinus rhythm and 33 (40%) had refractory ventricular tachycardia and/or ventricular fibrillation. Twelve patients (15%) underwent safe catheter ablation under venoarterial extracorporeal membrane oxygenation. After a median of 3 days (1-13 d) on extracorporeal membrane oxygenation support, 37 patients (45%) were successfully weaned off and 42% were alive 6 months post-ICU admission. Multivariable analysis retained ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm (odds ratio, 0.18; 95% CI, 0.06-0.52; p = 0.002) and age less than 50 years (odds ratio, 0.32; 95% CI, 0.18-0.89; p = 0.002) as being independent protective factors with 6-month survival, regardless of the underlying electrical storm cause. Conclusions: Among venoarterial extracorporeal membrane oxygenation-supported drug-refractory electrical storm patients, 42% survived 6 months post-ICU admission. Ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm and age less than 50 years were independently associated with better survival

Subcutaneos implantable cardioverter defibrillator and defibrillation testing: a propensity-matched pilot study

Background: To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT–) have been reported. Objective: The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT– patients. Methods: Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT– patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes. Results: Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT–) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT–; P = .404) as well as for ineffective shocks (5 DT– vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339–11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752–76.203; P = .003). Conclusion: In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts

Subcutaneous implantable cardioverter-defibrillator and defibrillation testing: A propensity-matched pilot study

Background: To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT–) have been reported. Objective: The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT– patients. Methods: Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT– patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes. Results: Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT–) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT–; P = .404) as well as for ineffective shocks (5 DT– vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339–11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752–76.203; P = .003). Conclusion: In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts