Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause.

Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

Anterior-Lateral Versus Anterior-Posterior Electrode Position for Cardioverting Atrial Fibrillation.

BACKGROUND: Smaller randomized studies have reported conflicting results regarding the optimal electrode position for cardioverting atrial fibrillation. However, anterior-posterior electrode positioning is widely used as a standard and believed to be superior to anterior-lateral electrode positioning. Therefore, we aimed to compare anterior-lateral and anterior-posterior electrode positioning for cardioverting atrial fibrillation in a multicenter randomized trial. METHODS: In this multicenter, investigator-initiated, open-label trial, we randomly assigned patients with atrial fibrillation scheduled for elective cardioversion to either anterior-lateral or anterior-posterior electrode positioning. The primary outcome was the proportion of patients in sinus rhythm after the first shock. The secondary outcome was the proportion of patients in sinus rhythm after up to 4 shocks escalating to maximum energy. Safety outcomes were any cases of arrhythmia during or after cardioversion, skin redness, and patient-reported periprocedural pain. RESULTS: We randomized 468 patients. The primary outcome occurred in 126 patients (54%) assigned to the anterior-lateral electrode position and in 77 patients (33%) assigned to the anterior-posterior electrode position (risk difference, 22 percentage points [95% CI, 13-30]; P<0.001). The number of patients in sinus rhythm after the final cardioversion shock was 216 (93%) assigned to anterior-lateral electrode positioning and 200 (85%) assigned to anterior-posterior electrode positioning (risk difference, 7 percentage points [95% CI, 2-12]). There were no significant differences between groups in any safety outcomes. CONCLUSIONS: Anterior-lateral electrode positioning was more effective than anterior-posterior electrode positioning for biphasic cardioversion of atrial fibrillation. There were no significant differences in any safety outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03817372.

Role for machine learning in sex-specific prediction of successful electrical cardioversion in atrial fibrillation?

OBJECTIVE: Electrical cardioversion is frequently performed to restore sinus rhythm in patients with persistent atrial fibrillation (AF). However, AF recurs in many patients and identifying the patients who benefit from electrical cardioversion is difficult. The objective was to develop sex-specific prediction models for successful electrical cardioversion and assess the potential of machine learning methods in comparison with traditional logistic regression. METHODS: In a retrospective cohort study, we examined several candidate predictors, including comorbidities, biochemistry, echocardiographic data, and medication. The outcome was successful cardioversion, defined as normal sinus rhythm immediately after the electrical cardioversion and no documented recurrence of AF within 3 months after. We used random forest and logistic regression models for sex-specific prediction. RESULTS: The cohort comprised 332 female and 790 male patients with persistent AF who underwent electrical cardioversion. Cardioversion was successful in 44.9% of the women and 49.9% of the men. The prediction errors of the models were high for both women (41.0% for machine learning and 48.8% for logistic regression) and men (46.0% for machine learning and 44.8% for logistic regression). Discrimination was modest for both machine learning (0.59 for women and 0.56 for men) and logistic regression models (0.60 for women and 0.59 for men), although the models were well calibrated. CONCLUSIONS: Sex-specific machine learning and logistic regression models showed modest predictive performance for successful electrical cardioversion. Identifying patients who will benefit from cardioversion remains challenging in clinical practice. The high recurrence rate calls for thoroughly informed shared decision-making for electrical cardioversion.

Cardioversion of atrial fibrillation in a real-world setting: non-vitamin K antagonist oral anticoagulants ensure a fast and safe strategy compared to warfarin.

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used as thromboembolic prophylaxis in cardioversion. We examined the waiting time to cardioversion and the outcomes in patients with non-valvular atrial fibrillation (AF) of > 48 h of duration who were treated with either NOACs or warfarin. Methods and results: Anticoagulation was handled in a structured, multidisciplinary AF-clinic. The objectives were the waiting time to cardioversion, and thromboembolism and major bleeding events within 60 days. In total, 2150 electrical cardioversions were performed; 684 (31.8%) of patients were on NOACs and 1466 (68.2%) were on warfarin. The waiting time to non-TOE-guided cardioversion was significantly shorter in the NOAC group compared with the warfarin group for all cardioversions (P < 0.001 for log-rank test) and for first-time cardioversions (P < 0.001 for log-rank test). For all non-TOE-guided cardioversions, 80% of procedures on NOACs and 67% of procedures on warfarin were performed within 25 days (P < 0.001). Thromboembolism occurred in one patient (0.15%) receiving NOAC and in two patients (0.14%) receiving warfarin (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.10-11.81). Major bleeding events occurred in four patients (0.58%) in the NOAC group and 11 patients (0.75%) in the warfarin group (RR 0.78; 95% CI 0.25-2.43). Conclusion: In a real-world clinical setting with anticoagulation handled in a structured multidisciplinary AF clinic, the waiting time to cardioversion was shorter with NOACs compared to warfarin. The rates of thromboembolism and major bleeding events were low, with NOACs shown to be as effective and safe as warfarin.

[A structured multidisciplinary approach ensures correct anticoagulation therapy to patients with atrial fibrillation]. / En struktureret tværfaglig tilgang sikrer patienter med atrieflimren korrekt antikoagulationsbehandling.

Atrial fibrillation (AF) is associated with an increased risk of stroke and mortality. Anticoagulation therapy reduces the risk of stroke in patients with AF. In a structured multidisciplinary AF-clinic correct anticoagulation treatment according to guidelines was achieved in 99% (170 out of 172 patients) compared to 79% (143 out of 179 patients) in the "usual care" period (p < 0.001). We propose establishment of structured multidisciplinary AF-clinics in Denmark to ensure optimal antithrombotic treatment and adherence to current guidelines.