Obesity is associated with impaired long-term success of pulmonary vein isolation:A plea for risk factor management before ablation

Aims: Obesity is an increasing health problem and is an important risk factor for the development of atrial fibrillation (AF). We investigated the association of body mass index (BMI) on the safety and long-term efficacy of pulmonary vein isolation (PVI) for drug-refractory AF. Methods: 414 consecutive patients who underwent transcatheter PVI for AF between 2003 and 2013 were included. Successful PVI was defined as absence of atrial arrhythmia on Holter monitoring or ECG, without and with antiarrhythmic drugs during follow-up. Obesity was defined as BMI≥30 kg/m². Results: Mean age was 56±10 years, 316 (76%) were male, 311 (75%) had paroxysmal AF and 111 (27%) were obese. After a mean follow-up of 46±32 months (1590 patient-years), freedom from atrial arrhythmia and antiarrhythmic drugs was significantly lower in patients with obesity compared with non-obese patients (30% vs 46%, respectively, P=0.005, log-rank 0.016). With antiarrhythmic drugs, freedom from atrial arrhythmia was 56% vs 68% (P=0.036). No differences in minor and major adverse events were observed between patients with obesity and non-obese patients (major 6% vs 3%, P=0.105, and minor 5% vs 5%, P=0.512). Sensitivity analyses demonstrated that BMI (as continuous variable) was associated with PVI outcome (HR 1.08, 95% CI 1.02 to 1.14, P=0.012). Conclusion: Obesity is associated with reduced efficacy of PVI for drug-refractory AF. No relation between obesity and adverse events was found

Identifying patients with atrial fibrillation recurrences after two pulmonary vein isolation procedures

INTRODUCTION: Pulmonary vein isolation (PVI) is an important treatment for atrial fibrillation (AF). However, many patients need more than one procedure to maintain long-term sinus rhythm. Even after two PVIs some may suffer from AF recurrences. We aimed to identify characteristics of patients who fail after two PVI procedures. METHODS AND RESULTS: We included 557 consecutive patients undergoing a first PVI procedure with a second-generation 28 mm cryoballoon. Follow-up procedures were performed using radiofrequency ablation targeting reconnected PVs only. Recurrent AF was defined as any episode of AF lasting >30 s on ECG or 24 hour Holter monitoring performed at 3, 6 and 12 months post procedure. Mean age was 59.1±10.2 years, 383 (68.8%) were male, 448 (80.4%) had paroxysmal AF and the most common underlying condition was hypertension (36.6%). A total of 140/557 (25.1%) patients underwent redo procedure with PVI only. Of these patients 45 (32.4%) had recurrence of AF. These patients were comparable regarding age and sex to those in sinus rhythm after one or two procedures. Multivariate logistic regression showed that non-paroxysmal AF (OR 1.08 (95% CI 1.01 to 1.15), estimated glomerular filtration rate (OR 0.96, 95% CI 0.94 to 0.99), bundle branch block (OR 4.17, 95% CI 1.38 to 12.58), heart failure (OR 4.17, 95% CI 1.38 to 12.58) and Left Atrium Volume Index (OR 1.04, 95% CI 1.01 to 1.08) were associated with AF recurrence after two PVIs. The area under the curve for the identified risk factors was 0.74. CONCLUSIONS: Using a PVI-only approach, recurrence of AF after two AF ablation procedures is associated with more advanced underlying disease and persistent types of AF

Verapamil versus digoxin and acute versus routine serial cardioversion for the improvement of rhythm control for persistent atrial fibrillation

ObjectivesThe VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF.BackgroundRhythm control is desirable in patients suffering from symptomatic AF.MethodsA total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute(within 24 h) and 70 (49%) patients to the routineserial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 × 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months.ResultsAt baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02).ConclusionsAn acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy

Three female patients with Danon disease presenting with predominant cardiac phenotype:a case series

Background: Danon disease is a rare X-linked multisystemic disorder that has primarily been described in male patients. Case summary: We present three female patients with Danon disease with a predominantly cardiac phenotype in whom disease onset and expression was very different from that of male patients. Case 1 was first admitted for acute heart failure and then readmitted a few months later for cardiac shock, necessitating mechanical support, and heart transplantation. Case 2 had complex arrhythmias for which many antiarrhythmic drugs were tried with only limited success. Her disease accelerated after her first pregnancy, and she showed reduced left ventricular function and dilated cardiomyopathy. Case 3 was referred for near syncope and ablated for an accessory pathway; she had extensive left ventricular hypertrophy. In all three cases, a final diagnosis of Danon disease was only made after genetic testing that identified a causal variant in the lysosome-associated membrane protein 2 gene. Discussion: Danon disease in female patients is a challenging diagnosis that may not be identified until genetic testing has been performed

Dynamic location problems with limited look-ahead

Background Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. Methods and Results The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications.Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N 195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. Conclusions This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N 195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction diseas

Pulmonary vein anatomy addressed by computed tomography and relation to success of second-generation cyroballoon ablation in paroxysmal atrial fibrillation

BACKGROUND: Cryoballoon isolation is considered a safe and effective treatment for atrial fibrillation (AF). However, recurrence of AF after first cryoballoon ablation occurs in ~30% of patients. Pre-procedurally identifying patients at risk of AF recurrence could be beneficial. HYPOTHESIS: Our aim was to determine how pulmonary vein (PV) anatomy influences the recurrence of AF using the second-generation cryoballoon in patients with paroxysmal AF. METHODS: We included 88 consecutive patients with paroxysmal AF undergoing PVI procedure with a second-generation 28-mm cryoballoon. All patients were evaluated at 3, 6 and 12 months using a 12-lead ECG and 24-hour Holter monitoring. Pulmonary vein (PV) anatomy was assessed by creating three dimensional models using computed tomography (CT) segmentations of the left atrium. RESULTS: Fifty-one patients (61%) had left PVs with a shared carina, 35 patients (42%) had a shared right carina. Nine patients (11%) were classified having a right middle PV. In total 17 (20.2%) of patients had a left common PV. At 12 months, 14 patients (17%) had experienced AF recurrence. Neither PV ovality, variant anatomy, the presence of shared carina nor a common left pulmonary vein was a predictor for AF recurrence. CONCLUSIONS: No specific characteristics of PV dimensions nor morphology were associated with AF recurrence after cryoballoon ablation in patients with paroxysmal AF. This article is protected by copyright. All rights reserved

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

INTRODUCTION Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression