Prevalence and determinants of atrial fibrillation progression in paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF. METHODS: In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression. RESULTS: Mean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression. CONCLUSION: In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed. TRIAL REGISTRATION NUMBER: NCT02726698.

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.

First-line treatment of persistent and long-standing persistent atrial fibrillation with single-stage hybrid ablation: a 2-year follow-up study.

AIMS: This study evaluates the efficacy and safety of first-line single-stage hybrid ablation of (long-standing) persistent atrial fibrillation (AF), over a follow-up period of 2 years, and provides additional information on arrhythmia recurrences and electrophysiological findings at repeat ablation. METHODS AND RESULTS: This is a prospective cohort study that included 49 patients (65% persistent AF; 35% long-standing persistent AF) who underwent hybrid ablation as first-line ablation treatment (no previous endocardial ablation). Patients were relatively young (57.0 ± 8.5 years) and predominantly male (89.8%). Median CHA2DS2-VASc score was 1.0 (0.5; 2.0) and mean left atrium volume index was 43.7 ± 10.9 mL/m2. Efficacy was assessed by 12-lead electrocardiography and 72-h Holter monitoring after 3, 6, 12, and 24 months. Recurrence was defined as AF/atrial flutter (AFL)/tachycardia (AT) recorded by electrocardiography or Holter monitoring lasting >30 s during 2-year follow-up. At 2-year follow-up, single and multiple procedure success rates were 67% and 82%, respectively. Two (4%) patients experienced a major complication (bleeding) requiring intervention following hybrid ablation. Among the 16 (33%) patients who experienced an AF/AFL/AT recurrence, 13 (81%) were ATs/AFLs and only 3 (19%) were AF. Repeat ablation was performed in 10 (20%) patients and resulted in sinus rhythm in 7 (70%) at 2-year follow-up. CONCLUSION: First-line single-stage hybrid AF ablation is an effective treatment strategy for patients with persistent and long-standing persistent AF with an acceptable rate of major complications. Recurrences are predominantly AFL/AT that can be successfully ablated percutaneously. Hybrid ablation seems a feasible approach for first-line ablation of (long-standing) persistent AF.

Antiarrhythmic drugs in patients with early persistent atrial fibrillation and heart failure: results of the RACE 3 study.

AIMS: Maintaining sinus rhythm in patients with persistent atrial fibrillation (AF) is challenging. We explored the efficacy of class I and III antiarrhythmic drugs (AADs) in patients with persistent AF and mild to moderate heart failure (HF). METHODS AND RESULTS: In the RACE 3 trial, patients with early persistent symptomatic AF and short history of mild to moderate HF with preserved or reduced left ventricular ejection fraction (LVEF) were randomized to targeted or conventional therapy. Both groups received AF and HF guideline-driven treatment. Additionally, the targeted-group received mineralocorticoid receptor antagonists, statins, angiotensin-converting enzyme inhibitors and/or receptor blockers, and cardiac rehabilitation. Class I and III AADs could be instituted in case of symptomatic recurrent AF. Eventually, pulmonary vein isolation could be performed. Primary endpoint was sinus rhythm on 7-day Holter after 1-year. Included were 245 patients, age 65 ± 9 years, 193 (79%) men, AF history was 3 (2-6) months, HF history 2 (1-4) months, 72 (29.4%) had HF with reduced LVEF. After baseline electrical cardioversion (ECV), 190 (77.6%) had AF recurrences; 108 (56.8%) received class I/III AADs; 19 (17.6%) flecainide, 36 (33.3%) sotalol, 3 (2.8%) dronedarone, 50 (46.3%) amiodarone. At 1-year 73 of 108 (68.0%) patients were in sinus rhythm, 44 (40.7%) without new AF recurrences. Maintenance of sinus rhythm was significantly better with amiodarone [n = 29/50 (58%)] compared with flecainide [n = 6/19 (32%)] and sotalol/dronedarone [n = 9/39 (23%)], P = 0.0064. Adverse events occurred in 27 (25.0%) patients, were all minor and reversible. CONCLUSION: In stable HF patients with early persistent AF, AAD treatment was effective in nearly half of patients, with no serious adverse effects reported.

Temporal patterns and short-term progression of paroxysmal atrial fibrillation: data from RACE V.

AIMS: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. METHODS AND RESULTS: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. CONCLUSIONS: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02726698.

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF. METHODS: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation. RESULTS: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13). CONCLUSIONS: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Pulmonary vein anatomy addressed by computed tomography and relation to success of second-generation cryoballoon 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. 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 PV 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.

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.

Totally Thoracoscopic Pulmonary Vein Isolation: A Simplified Technique.

Since the introduction of thoracoscopic ablation for atrial fibrillation (AF), the field of minimally invasive AF treatment has evolved toward an established treatment option for AF, with an overall 2-year antiarrhythmic drug free success rate of 77%. Complications are usually minor, and the incidence of bleeding needing conversion to sternotomy or (mini-)thoracotomy varies between 0% and 1.6%. Bleeding is often related to encircling the pulmonary veins, which is a blind maneuver that has to be done without direct camera vision. We propose here a modified surgical technique to simplify the procedure, shorten the operating time, and lower the risk of complications.

Predictors of incident diabetes mellitus in Basrah, Iraq.

BACKGROUND: New-onset diabetes was associated with a 90% increase in risk of all-cause mortality and a 120% increase in risk of cardiovascular mortality compared with study participants without diabetes. The aim of this study was to study prospectively the predictors of incident diabetes mellitus in Basrah, Iraq, with special emphasis on predictive performance of the four anthropometric variables of obesity, namely body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHpR) or waist-to-height ratio (WHtR). MATERIAL AND METHODS: A total of 13,730 subjects (7,101 males and 6,629 females) diabetes-free at baseline were followed for a mean of 5 years (January 2001 to end of December 2006). RESULTS: There were 935 (6.80%) cases of incident diabetes (513 males and 422 females). All anthropometric indices (BMI, WC, WHpR, WHtR) were higher among those with incident diabetes (p < 0.001). In both sexes, WHpR has the strongest associations with incident diabetes that was gender-insensitive (AUC = 0.74 in males and 0.72 in females) followed by WC and then BMI which has the weakest association with incident diabetes. On multivariable logistic regression, only hypertension (OR 1.66; 95% CI 1.41-1.96; p < 0.001) was associated with incident diabetes. All anthropometric indices were significantly associated with incident diabetes except WHtR. There was no association between incident diabetes and gender, age, stroke, and ischemic heart disease. CONCLUSION: In both sexes, WHpR has the strongest associations with incident diabetes, followed by WC then BMI which has the weakest association with incident diabetes, while WHtR has no association. Hypertension is the only non-anthropometric variable associated with incident diabetes.

Cut-off values for anthropometric variables that confer increased risk of type 2 diabetes mellitus and hypertension in Iraq.

BACKGROUND: Body mass index (BMI) is often used to reflect total body fat amount (general obesity), whereas waist circumference (WC), waist-to-hip ratio (WHpR) or waist-to height ratio (WHtR) is used as a surrogate of body fat centralization (central obesity). The purpose of the present study was to identify cut-offs for BMI and upper-body adiposity (WC, WHpR, and WHtR) that, associated with increased risk of type 2 DM and hypertension in Iraqi adults, would be consistent with overweight and central adiposity. METHODS: This was a community-based cross-sectional survey for establishing cut-off values for BMI and upper-body adiposity (WC, WHpR or WHtR) associated with increased risk of type 2 DM and hypertension from one district in Southern Iraq, Basrah (Abu-Al-khasib). The total number of persons involved was 12,986 (6693 men and 6293 women), aged 45.6 +/- 15.7 years. RESULTS: The cut-off point in men associated with increased risk of type 2 DM and hypertension were BMI 25.4 and 24.9, WC 90 and 95 cm, WHpR 0.92 for both and WHtR 0.52 and 0.55, respectively. For women, the cut-off point associated with increased risk of type 2 DM and hypertension were BMI 26.1 and 26.5, WC 91 and 95 cm, WHpR 0.91 for both, and for WHtR 0.56 and 0.59, respectively. The best index for association with type 2 DM was WHpR with cut-off point of 0.92 for men and 0.91 for women. For hypertension, the best index is WHtR (with cut-off point of 0.55 for men and 0.59 for women), whereas the least reliable index was the BMI for both type 2 DM and hypertension. CONCLUSIONS: Our finding showed that, in Iraqi adults, WHpR has the strongest association with type 2 DM and WHtR for hypertension.