Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation

OBJECTIVES This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact on procedural outcome and long-term prognosis. BACKGROUND The prevalence of genetic variants associated with monomorphic VT among DCM is unknown. METHODS Ninety-eight consecutive patients (age 56 +/- 15 years; 84% men, left ventricular ejection fraction [LVEF] 39 12%) referred for DCM-VT ablation were included. Patients underwent electroanatomical mapping and testing of >= 55 cardiomyopathy-related genes. Mapping data were analyzed for low-voltage areas and abnormal potentials. LP/Pv-positive (LP/Pv+) patients were compared with LP/Pv-negative (LP/Pv-) patients and followed for VT recurrence and mortality. RESULTS In 37 (38%) patients, LP/Pv were identified, most frequently LMNA (n = 11 of 37, [30%]), 17N (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2 of 37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had tower LVEF (35 + 13% vs. LP/Pv-: 42 11%; p 0.005) and were less often men (n 27 [73%] vs. n 55 [90%] p 0.03). After a median follow-up of 2.4 years (interquartile range: 0.9 to 4.4 years), 63 (64%) patients had VT recurrence (LP/Pv+: 30 of 37 [81%] vs. LP/Pv-: 33 of 61 [54%]; p = 0.007). Twenty-eight patients (29%) died (LP/Pv +: 19 of 37 [51%] vs. LP/Pv-: 9 of 61 [15%]; p <0.001). The cumulative 2-year VT-free survival was 41% in the total cohort (LP/Pv+: 16% vs. LP/Pv-: 54%; p 0.001). The presence of LP/Pv (hazard ratio: 1.9; 95% confidence interval: 1.1 to 3.4; p = 0.02) and unipolar low-voltage area size/cm(2) increase (hazard ratio: 2.5; 95% confidence interval: 1.6 to 4.0; p <0.001) were associated with a decreased 2-year VT-free survival. CONCLUSIONS In patients with DCM-VT, a genetic cause is frequently identified. LP/Pv+ patients have a tower LVEF and more extensive VT substrates, which, in combination with disease progression, may contribute to the poor prognosis. Genetic testing in patients with DCM-VT should therefore be recommended. (C) 2020 by the American College of Cardiology Foundation

Corruption in the Middle East and the Limits of Conventional Approaches

Die Unzufriedenheit mit der verbreiteten Korruption war 2011/2012 eine wesentliche Ursache für die arabischen Unruhen und weitere Aufstände weltweit. Der Fall Jordanien zeigt allerdings, dass konventionelle Ansätze zur Bekämpfung von Korruption nicht ausreichen. Eine angemessene Strategie gegen Korruption muss diese als ein Problem der Verteilungsgerechtigkeit und nicht des Strafrechts verstehen. Wie in allen anderen arabischen Staaten ist die Unzufriedenheit in der Bevölkerung über die offensichtliche Korruption auch in Jordanien beträchtlich. Allerdings wird im Allgemeinen nicht über Fälle von Bestechung und Erpressung geklagt, die weniger häufig vorkommen, sondern über lokale Praktiken politischer Patronage und Begünstigung, die unter dem Begriff "Wasta" zusammengefasst werden. "Wasta" wurde bislang als Form der Korruption und strafrechtliches Problem angesehen, weshalb Versuche zur Eindämmung überwiegend ineffizient blieben: "Wasta"-Praktiken werden in der Regel nicht mit Rechtsverstößen verbunden, sondern bewegen sich innerhalb formal legaler Verfahren. Konventionelle Ansätze zur Bekämpfung von Korruption, die sich an rechtsstaatlichen Grundsätzen und Transparenz orientieren, sind deshalb nicht zielführend. Demokratisierung allein ist ebenfalls ungeeignet, das Problem „Wasta” zu lösen. In der parlamentarischen Praxis macht "Wasta" den Großteil der Aktivitäten aller Parlamentsmitglieder aus. Diese werden deshalb als persönliche Dienstleister für ihre Wahlbezirke und nicht als Mitglieder einer gesetzgebenden Körperschaft wahrgenommen. Gleichzeitig hält die Bevölkerung das Parlament für eine zutiefst korrupte Institution. "Wasta" wird problematisch, wenn diese Praxis zu einem ungleichen Zugang der Bürger zu öffentlichen Ressourcen führt. Statt sich nur auf politische und administrative Reformen zu konzentrieren, muss der Fokus der Bekämpfung auf den (Wieder-)Aufbau wohlfahrtsstaatlicher Strukturen gelegt werden, zu denen alle Bürger gleichermaßen Zugang haben

Design and rationale of DUTCH-AF:a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation

Introduction Anticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and AF-related adverse events in practice-based patient cohorts, in particular for non-vitamin K oral anticoagulants (NOAC). With the creation of DUTCH-AF, a nationwide longitudinal AF registry, we aim to provide clinical data and answer questions on the (anticoagulant) management over time and of the clinical course of patients with newly diagnosed AF in routine clinical care. Within DUTCH-AF, our current aim is to assess the effect of non-adherence and non-persistence of anticoagulation therapy on clinical adverse events (eg, bleeding and stroke), to determine predictors for such inadequate anticoagulant treatment, and to validate and refine bleeding prediction models. With DUTCH-AF, we provide the basis for a continuing nationwide AF registry, which will facilitate subsequent research, including future registry-based clinical trials. Methods and analysis The DUTCH-AF registry is a nationwide, prospective registry of patients with newly diagnosed 'non-valvular' AF. Patients will be enrolled from primary, secondary and tertiary care practices across the Netherlands. A target of 6000 patients for this initial cohort will be followed for at least 2 years. Data on thromboembolic and bleeding events, changes in antithrombotic therapy and hospital admissions will be registered. Pharmacy-dispensing data will be obtained to calculate parameters of adherence and persistence to anticoagulant treatment, which will be linked to AF-related outcomes such as ischaemic stroke and major bleeding. In a subset of patients, anticoagulation adherence and beliefs about drugs will be assessed by questionnaire. Ethics and dissemination This study protocol was approved as exempt for formal review according to Dutch law by the Medical Ethics Committee of the Leiden University Medical Centre, Leiden, the Netherlands. Results will be disseminated by publications in peer-reviewed journals and presentations at scientific congresses

Long-term follow-up of thoracoscopic ablation in long-standing persistent atrial fibrillation

OBJECTIVES: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic ablation has shown effective at creating transmural lesions around the pulmonary veins and box; however, long-term rhythm follow-up data are lacking. This study aims, for the first time, to assess the long-term outcomes of thoracoscopic pulmonary vein and box ablation in LSPAF. METHODS: Rhythm follow-up consisted of continuous rhythm monitoring using implanted loop recorders or 24-h Holter recordings. Rhythm status and touch-up interventions were assessed up to 5 years. RESULTS: Seventy-seven patients with symptomatic LSPAF underwent thoracoscopic ablation in 2 centres. Freedom from atrial arrhythmias at 5 years was 50% following a single thoracoscopic procedure and 68% allowing endocardial touch-up procedures (performed in 21% of patients). The mean atrial fibrillation burden in patients with continuous monitoring was reduced from 100% preoperatively to 0.1% at the end of the blanking period and 8.0% during the second year. Antiarrhythmic drug use decreased from 49.4% preoperative to 12.1% and 14.3% at 2 and 5 years, respectively (P < 0.001). Continuous rhythm monitoring resulted in higher recurrence detection rates compared to 24-h Holter monitoring at 2-year follow-up (hazard ratio: 6.5, P = 0.003), with comparable recurrence rates at 5-year follow-up. CONCLUSIONS: Thoracoscopic pulmonary vein and box isolation are effective in long-term restoration of sinus rhythm in LSPAF, especially when complemented by endocardial touch-up procedures, as demonstrated by the 68% freedom rate at 5 years. Continuous rhythm monitoring revealed earlier, but not more numerous documentation of recurrences at 5-year follow-up

Natriuretic peptide levels predict recurrence of atrial fibrillation after radiofrequency catheter ablation

Background The presence of atrial fibrillation (AF) is related to increased levels of natriuretic peptides. In addition, increased natriuretic peptide levels are predictive of the development of AF. However, the role of natriuretic peptides to predict recurrence of AF after radiofrequency catheter ablation (RFCA) is controversial. Objective The study aimed to investigate the role of natriuretic peptides in the prediction of AF recurrence after RFCA for AF. Methods Pre-procedural amino-terminal pro-atrial natriuretic peptide (NT-proANP) and amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) plasma levels were determined in 87 patients undergoing RFCA for symptomatic drug-refractory AF. In addition, a comprehensive clinical and echocardiographic evaluation was performed at baseline. Left atrial volumes, left ventricular volumes, and function (systolic and diastolic) were assessed. During a 6-month follow-up period, AF recurrence was monitored and defined as any registration of AF on electrocardiogram or an episode of AF longer than 30 seconds on 24-hour Holter monitoring. The role of natriuretic peptide plasma levels to predict AF recurrence after RFCA was studied. Results During follow-up, 66 patients (76%) maintained sinus rhythm, whereas 21 patients (24%) had AF recurrence. Patients with AF recurrence had higher baseline natriuretic peptide levels than patients who maintained sinus rhythm (NT-proANP 3.19 nmol/L [2.55-4.28] vs 2.52 nmol/L [1.69-3.55], P = .030; NT-proBNP 156.4 pg/mL [64.1-345.3] vs 84.6 pg/mL [43.3-142.7], P = .036). However, NT-proBNP was an independent predictor of AF recurrence, whereas NT-proANP was not. Moreover, NT-proBNP had an incremental value over echocardiographic characteristics to predict AF recurrence after RFCA. Conclusion Baseline NT-proBNP plasma level is an independent predictor of AF recurrence after RFCA. (Am Heart J 2011;161:197-203.)Arrhythmia

Thromboembolic and bleeding complications during interruptions and after discontinuation of anticoagulant treatment in patients with atrial fibrillation and active cancer:A daily practice evaluation

Background and aims: Cancer provides challenges to the continuity of anticoagulant treatment in patients with atrial fibrillation (AF), e.g. through cancer-related surgery or complications. We aimed to provide data on the incidence and reasons for interrupting and discontinuing anticoagulant treatment in AF patients with cancer and to assess its contribution to the risk of thromboembolism (TE) and major bleeding (MB). Methods: This retrospective study identified AF patients with cancer in two hospitals between 2012 and 2017. Data on anticoagulant treatment, TE and MB were collected during two-year follow-up. Incidence rates (IR) per 100 patient-years and adjusted hazard ratios (aHR) were obtained for TE and MB occurring during on- and off-anticoagulant treatment, during interruption and after resumption, and after permanent discontinuation. Results: 1213 AF patients with cancer were identified, of which 140 patients permanently discontinued anticoagulants and 426 patients experienced one or more interruptions. Anticoagulation was most often interrupted or discontinued due to cancer-related treatment (n = 441, 62 %), bleeding (n = 129, 18 %) or end of life (n = 36, 5 %). The risk of TE was highest off-anticoagulation and during interruptions, with IRs of 19 (14–25)) and 105 (64–13), and aHRs of 3.1 (1.9–5.0) and 4.6 (2.4–9.0), respectively. Major bleeding risk were not only increased during an interruption, but also in the first 30 days after resumption, with IRs of 33 (12–72) and 30 (17–48), and aHRs of 3.3 (1.1–9.8) and 2.4 (1.2–4.6), respectively. Conclusions: Interruption of anticoagulation therapy harbors high TE and MB risk in AF patients with cancer. The high incidence rates call for better (periprocedural) anticoagulant management strategies tailored to the cancer setting

Relationship between obstructive coronary artery disease and abnormal stress testing in patients with paroxysmal or persistent atrial fibrillation

Atrial fibrillation (AF) has been linked to the presence of underlying coronary artery disease (CAD). However, whether the higher burden of CAD observed in AF patients translates into higher burden of myocardial ischemia is unknown. In 87 patients (71% male, mean age 61 ± 10 years) with paroxysmal or persistent AF and without history of CAD, MSCT coronary angiography and stress testing (exercise ECG test or myocardial perfusion imaging) were performed. CAD was classified as obstructive (≥50% luminal narrowing) or not. Stress tests were classified as normal or abnormal. A population of 122 patients without history of AF, similar to the AF group as to age, gender, symptomatic status and pre-test likelihood, served as a control group. Based on MSCT, 17% of AF patients were classified as having no CAD, whereas 43% showed non-obstructive CAD and the remaining 40% had obstructive CAD. A positive stress test was observed in 49% of AF patients with obstructive CAD. Among non-AF patients, 34% were classified as having no CAD, while 41% showed non-obstructive CAD and 25% had obstructive CAD (P = 0.013 compared to AF patients). A positive stress test was observed in 48% of non-AF patients with obstructive CAD. In conclusion, the higher burden of CAD observed in AF patients is not associated to higher burden of myocardial ischemia