Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart Failure Progression and Mortality: A Post-Hoc Propensity Score-Matched Analysis of the TOPCAT Americas Trial.

AIMS: Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. METHODS AND RESULTS: We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. CONCLUSION: Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. TRIAL REGISTRATION: TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulant Therapy).

BACKGROUND: The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113 patients with atrial fibrillation. Those with prosthetic heart valves, significant mitral stenosis, and valvular heart disease (VHD) requiring intervention were excluded. Others with VHD were included. METHODS: This is a post hoc analysis of the RE-LY trial. RESULTS: There were 3950 patients with any VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral stenosis. At baseline, patients with any VHD had more heart failure, coronary disease, renal impairment, and persistent atrial fibrillation. Patients with any VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR, 1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95 with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR, 0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD (HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR, 0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds and death rates for dabigatran 150 and 110 mg were lower compared with warfarin independently of the presence of VHD. CONCLUSIONS: The presence of any VHD did not influence the comparison of dabigatran with warfarin. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion.

BACKGROUND: The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared dabigatran 110 mg BID (D110) and 150 mg BID (D150) with warfarin for stroke prevention in 18 113 patients with nonvalvular atrial fibrillation. METHODS AND RESULTS: Cardioversion on randomized treatment was permitted. Precardioversion transesophageal echocardiography was encouraged, particularly in dabigatran-assigned patients. Data from before, during, and 30 days after cardioversion were analyzed. A total of 1983 cardioversions were performed in 1270 patients: 647, 672, and 664 in the D110, D150, and warfarin groups, respectively. For D110, D150, and warfarin, transesophageal echocardiography was performed before 25.5%, 24.1%, and 13.3% of cardioversions, of which 1.8%, 1.2%, and 1.1% were positive for left atrial thrombi. Continuous treatment with study drug for ≥3 weeks before cardioversion was lower in D110 (76.4%) and D150 (79.2%) compared with warfarin (85.5%; P<0.01 for both). Stroke and systemic embolism rates at 30 days were 0.8%, 0.3%, and 0.6% (D110 versus warfarin, P=0.71; D150 versus warfarin, P=0.40) and similar in patients with and without transesophageal echocardiography. Major bleeding rates were 1.7%, 0.6%, and 0.6% (D110 versus warfarin, P=0.06; D150 versus warfarin, P=0.99). CONCLUSIONS: This study is the largest cardioversion experience to date and the first to evaluate a novel anticoagulant in this setting. The frequencies of stroke and major bleeding within 30 days of cardioversion on the 2 doses of dabigatran were low and comparable to those on warfarin with or without transesophageal echocardiography guidance. Dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion.

Intracardiac echocardiography-guided cardiac resynchronization therapy: technique and clinical application.

BACKGROUND: We undertook a pilot investigation to evaluate the feasibility of a novel technique using intracardiac echocardiography (ICE) for intraoperative assessment of cardiac resynchronization therapy (CRT). METHODS: We evaluated ICE intraoperative imaging of left ventricular (LV) function and aortic valvular flow as well as safety of implementation. ICE was used to guide CRT system lead placement, assess impact of pacing modes, and optimization of device programming. RESULTS: Twenty-three patients underwent ICE imaging. ICE showed global hypokinesis in six patients, regional wall motion abnormality only in 10 patients, and both in seven patients. Optimized CRT modes included mean atrioventricular (AV) interval of 170 ms and interventricular timing using simultaneous right ventricular (RV)-LV pacing (five patients), LV pacing only (one patient), and sequential LV to RV stimulation (15 patients) or RV to LV stimulation (two patients). ICE-guided CRT acutely improved mean left ventricular ejection fraction (LVEF) from 24 +/- 9% to 41 +/- 1% (P < 0.00001). During follow-up of 3-24 (mean 11) months, New York Heart Association class improved in all patients from a mean of 3.2 +/- 0.4 at implant to 1.6 +/- 0.7 (P < 0.0001), with improvement of LVEF from 19 +/- 7% to 34 +/- 12% (P = 0.0001). Actuarial survival was 83% at 12 months. CONCLUSIONS: (1) ICE imaging is reliable and safe for continuous intraoperative imaging of LV wall motion, and assesses baseline status and impact of CRT interventions.(2) Intraoperative ICE-guided CRT optimization resulted in an increase in LVEF acutely and consistent improvement in heart failure.(3) Sequential biventricular pacing and longer AV interval programming were more often used in ICE-guided CRT.

Chronic antithrombotic therapy in post-myocardial infarction patients.

Because 1.1 million myocardial infarctions occur in the United States alone each year, and 450,000 of them are recurrent infarctions, which carry an inherently greater risk of death and disability than first events, the importance of secondary prevention strategies that can be implemented widely is unparalleled in health care. Antithrombotic therapies, both antiplatelet and anticoagulant, have become the mainstays of these strategies. This article covers the use of chronic antiplatelet and anticoagulation agents after myocardial infarction. It does not include the management of these patients in the acute phase.

Diastolic dysfunction and atrial fibrillation.

INTRODUCTION: Isolated diastolic heart failure (DHF) is defined as heart failure with preserved left ventricular (LV) systolic function in the absence of valve disease. DHF is a clinical diagnosis confirmed by echocardiography and is presumed to be due to diastolic dysfunction (DD). DD is characterized by abnormalities in relaxation and/or distensibility (restriction) of the left ventricle (LV). DHF accounts for 30% to 50% of patients with heart failure and is an independent predictor of atrial fibrillation (AF) in the elderly. AIM: This paper will describe the diagnosis of DD in both sinus rhythm and AF as well report on agents used in the treatment of DHF and prevention of AF in DHF. DIAGNOSIS IN SINUS RHYTHM: Early DD is identified by Doppler determined mitral inflow measurements: The ratio of the peak velocity of the early filling (E) wave to the atrial contraction (A) wave, E/A is <1, the deceleration time (DT) is slow (>240 ms), the isovolumic relaxation period (IRP) is prolonged (>110 ms). In Moderate DD, the LV stiffens with elevated left atrial pressure resulting in "pseudonormal" filling pattern with E/A ratio >1. This is unmasked by pulmonary vein measurements with the systolic forward flow (S) being less than (approximately 50%) diastolic forward flow wave (D). Retrograde flow wave (A (R)) is increased >0.25 m/s. As the LV stiffens, restrictive features develop resulting in rapid early filling with E/A ratio >2, shortened DT <150 ms and IRP <60 ms. The A (R) wave is increased in amplitude >0.35 m/s and duration >30 ms. Early diastolic filling reflected by tissue Doppler determination of mitral annulus motion velocity (E') is reduced in DD. The E/E' ratio correlates well with filling pressures. DIAGNOSIS IN AF: Atrial contraction is absent and therefore measurements independent of atrial influence such as DT, IRP, E/E' ratio and S wave are used. THERAPY FOR DHF AND AF PREVENTION: While not well established, Treatment with ACE-inhibitors, angiotensin receptor blockers (ARBs) and aldosterone antagonists have shown objective improvement in DHF and ARBs have been found to decrease the incidence of AF. Candesartan decreases the incidence of AF in patients with symptomatic heart failure and preserved LV systolic function. There are ongoing studies of Irbesartan and spironolactone to evaluate their effect on DHF treatment. CONCLUSION: Diagnosis of DD is made by echocardiography in patients with sinus rhythm or in patients with AF. Randomized controlled trials in patients with DHF are under way. The treatment of DHF and AF prevention will continue to evolve.

The future of implantable defibrillator and cardiac resynchronization therapy trials.

Implantable cardioverter defibrillator (ICD) trials were initially limited to survivors of sudden death. The focus of defibrillator trials in the last decade has been in prophylactic implantation of the device in high risk populations for the prevention of sudden cardiac death. It is the contention in this review that the new focus for implantable defibrillator trials in 2008 and beyond will be on more selective and focused use of this therapy. This could be achieved by selecting ICD patients based on their pathophysiologic and genetic risk. Increasing effort will also be placed on using the device for prevention of spontaneous malignant ventricular tachyarrhythmias and the index clinical sudden death event. Finally, implantable defibrillators will be used in combination in a "hybrid" therapy approach. ICDs will be increasingly combined either with ventricular tachycardia ablation or ventricular fibrillation ablation using catheter techniques. With the addition of cardiac resynchronization therapy in these devices, new clinical trials that use cardiac resynchronization therapy as an early intervention in specific high risk heart failure populations and refinement of the CRT technique to improved optimal results are in progress. Finally, combining ICD devices and regenerative medicine approaches to myocardial replacement therapy are being explored.

Critical Role of the Posterior Left Atrium in the Perpetuation of Persistent Atrial Fibrillation and the Hybrid Ablation Approach for Persistent Atrial Fibrillation Management: A Single-center Outcomes Study.

Atrial fibrillation (AF) is the most common heart rhythm disorder and a growing major public health burden. AF ablation is considered to be the preferred rhythm control strategy for symptomatic drug-refractory paroxysmal and persistent AF (PRAF). To date, the long-term ablation success rates of pulmonary vein isolation (PVI) for PRAF and longstanding PRAF (LS-PRAF) have not paralleled those of paroxysmal AF. Additional concomitant ablation strategies such as linear ablation lesions in the left and right atria; autonomic ganglionic plexi ablation; ablation directed by complex fractionated atrial electrograms; ablation of nonpulmonary vein (PV) triggers; radiofrequency ablation of the vein of Marshall; and, most recently, focal impulse and rotor ablation/modulation have shown modest improvement in terms of efficacy, but no reproducible outcomes. Here, we describe the critical role of the posterior left atrium (LA) and PV region in the development and progression of PRAF and LS-PRAF. We discuss the results of single-center outcomes data for convergent or hybrid AF ablation of the posterior LA and PV region (endocardial PVI + minimally invasive epicardial posterior LA ablation). This epicardial ablation approach, combined with endocardial ablation, is an option for patients with PRAF and LS-PRAF. More definitive clinical trials are needed.

Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study).

This is the first evaluation of dabigatran, an oral direct thrombin inhibitor, in patients with atrial fibrillation (AF). Patients (n = 502) were randomized to receive blinded doses of 50-, 150-, or 300-mg dabigatran twice daily alone or combined with 81- or 325-mg aspirin or open-label warfarin administered to achieve an international normalized ratio of 2 to 3 for 12 weeks. Dabigatran plasma concentrations, activated partial thromboplastin time, D-dimer, urinary 11-dehydrothromboxane B(2) (DTB2), and liver function were measured at baseline and at 1, 2, 4, 8, and 12 weeks. Clinical end points were assessed according to the treatment received at the time of the event. Overall, 92% of patients completed the study. Major hemorrhages were limited to the group treated with 300-mg dabigatran plus aspirin (4 of 64), and the incidence was significant versus 300-mg dabigatran alone (0 of 105, p <0.02). Total bleeding events were more frequent in the 300-mg (39 of 169, 23%) and 150-mg (30 of 169, 18%) dabigatran groups compared with the 50-mg groups (7 of 107, 7%; p = 0.0002 and p = 0.01, respectively). Thromboembolic events were limited to the 50-mg dabigatran dose groups (2 of 107, 2%). The mean trough d-dimer measurements were suppressed for the 2 highest doses of dabigatran and warfarin (international normalized ratio of 2 to 3). Aminotransferase levels >3 times the upper limit of normal were observed in 0.9% of the dabigatran recipients and in none of the warfarin recipients. Two dabigatran recipients had aminotransferase levels >5 times the upper limit of normal as a result of gallstones, which resolved. Trough activated partial thromboplastin time values were 1.2, 1.5, and 1.8 times the baseline level for the 50-, 150-, and 300-mg dabigatran groups, respectively. DTB2 concentrations after 12 weeks of 50-, 150-, and 300-mg dabigatran treatment were increased by 31%, 17%, and 23%, respectively, versus baseline (p = 0.02, p = 0.03, and p = 0.0004). In conclusion, major bleeding events were limited to patients treated with dabigatran 300 mg plus aspirin and thromboembolic episodes were limited to the 50-mg dabigatran groups. The 2 highest doses of dabigatran suppress D-dimer concentrations. Serious liver toxicity was not seen. The significance of the increase of DTB2 concentrations in dabigatran-treated patients needs resolution.

Comparison of Characteristics and Outcomes of Dabigatran Versus Warfarin in Hypertensive Patients With Atrial Fibrillation (from the RE-LY Trial).

Hypertension is frequent in patients with atrial fibrillation (AF) and is an independent risk factor for stroke. The Randomized Evaluation of Long Term Anticoagulant TherapY (RE-LY) trial found dabigatran 110 mg (D110) and 150 mg twice daily (D150) noninferior or superior to warfarin for stroke reduction in patients with AF, with either a reduction (D110) or similar rates (D150) of major bleeding. Baseline characteristics and outcomes were compared in patients with and without hypertension. The quality of blood pressure control was also assessed. In RE-LY, 14,283 patients (78.9%) had hypertension. The mean blood pressure at baseline was 132.6 ± 17.6/77.7 ± 10.6 and 124.8 ± 16.7/74.6 ± 10.0 mm Hg for patients with and without hypertension, respectively. More patients with hypertension were diabetic (25.6% vs 14.8%, p <0.001), women (38.6% vs 28.3%, p <0.001), and had greater CHADS2 (2.3 vs 1.4, p <0.001) and CHA2DS2-VASc scores (3.8 vs 2.8, p <0.001). Mean blood pressure in all treatment arms in hypertensive patients was similar (130 ± 18/76 ± 11 mm Hg) during the trial. The efficacy and safety of D110 and D150 compared to warfarin were similar (p = nonsignificant) in hypertensive (stroke/systemic embolism rate of 1.47%, 1.20%, and 1.81% and major bleed rate of 2.89%, 3.70%, and 3.69% in the D110, D150, and W, respectively) and normotensive patients (stroke/systemic embolism rate of 1.79%, 0.78%, and 1.36% and major bleed rate of 2.84%, 2.37%, and 3.03% per year in the D110, D150, and W, respectively). Hypertensive patients had more major bleeds (3.39% vs 2.76%; p = 0.007). Intracranial bleeds were similar (0.47% vs 0.31%; p = 0.12). In conclusion, patients with hypertension in RE-LY were more likely female, diabetic, with a greater CHADS2 and CHA2DS2-VASc scores. Blood pressure control in RE-LY was excellent. The benefits of dabigatran over warfarin, including a substantial reduction of intracranial hemorrhage, were similar in both hypertensive and non-hypertensive patients.

Left atrial reverse remodeling and prevention of progression of atrial fibrillation with atrial resynchronization device therapy utilizing dual-site right atrial pacing in patients with atrial fibrillation refractory to antiarrhythmic drugs or catheter ablation.

INTRODUCTION: Dual-site right atrial pacing (DAP) produces electrical atrial resynchronization but its long-term effect on the atrial mechanical function in patients with refractory atrial fibrillation (AF) has not been studied. METHODS: Drug-refractory paroxysmal (PAF) and persistent AF (PRAF) patients previously implanted with a dual-site right atrial pacemaker (DAP) with minimal ventricular pacing modes (AAIR or DDDR mode with long AV delay) were studied. Echocardiographic structural (left atrial diameter [LAD] and left ventricular [LV] end diastolic diameter [EDD], end systolic diameter [ESD]) and functional (ejection fraction [EF]) parameters were serially assessed prior to, after medium-term (n = 39) and long-term (n = 34) exposure to DAP. RESULTS: During medium-term follow-up (n = 4.5 months), there was improvement in left atrial function. Mean peak A wave flow velocity increased with DAP as compared to baseline (75 ± 19 vs. 63 ± 23 cm/s, p = 0.003). The long-term impact of DAP was studied with baseline findings being compared with last follow-up data with a mean interval of 37 ± 25 (range 7-145) months. Mean LAD declined from 45 ± 5 mm at baseline to 42 ± 7 mm (p = 0.003). Mean LVEF was unchanged from 52 ± 9 % at baseline and 54 ± 6 % at last follow-up (p = 0.3). There was no significant change in LV dimensions with mean LVEDD being 51 ± 6 mm at baseline and 53 ± 5 mm at last follow-up (p = 0.3). Mean LVESD also remained unchanged from 35 ± 6 mm at baseline to 33 ± 6 mm at last follow-up (p = 0.47). During long-term follow-up, 30 patients (89 %) remained in sinus or atrial paced rhythm as assessed by device diagnostics at 3 years. CONCLUSIONS: DAP can achieve long-term atrial reverse remodeling and preserve LV systolic function. DAP when added to antiarrhythmic drug (AAD) and/or catheter ablation (ABL) maintains long-term rhythm control and prevents AF progression in elderly refractory AF patients. Reverse remodeling with DAP may contribute to long-term rhythm control.

Continuous warfarin versus periprocedural dabigatran to reduce stroke and systemic embolism in patients undergoing catheter ablation for atrial fibrillation or left atrial flutter.

PURPOSE: Left atrial catheter ablation for patients with atrial fibrillation (AF) requires periprocedural anticoagulation to minimize thromboembolic complications. High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported, raising concerns regarding its safety during left atrial catheter ablation. We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin, at a single high-volume AF ablation center. METHODS: We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at Vanderbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months. Patient cohorts were divided into two groups, those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on dose-adjusted warfarin, with or without low-molecular-weight heparin bridging. Dabigatran was held 24-30 h pre-procedure and restarted 4-6 h after hemostasis was achieved. We evaluated all thromboembolic and bleeding complications at 3 months post-ablation. RESULTS: A total of 254 patients underwent left atrial catheter ablation for atrial fibrillation or left atrial flutter. Periprocedural anticoagulation utilized dabigatran in 122 patients and warfarin in 135 patients. Three late thromboembolic complications occurred in the dabigatran group (2.5 %), compared with one (0.7 %) in the warfarin group (p = 0.28). The dabigatran group had similar minor bleeding (2.5 vs. 7.4 %, p = 0.07), major bleeding (1.6 vs. 0.7 %, p = 0.51), and composite of bleeding and thromboembolic complications (6.6 vs. 8.9 %, p = 0.49) when compared to warfarin. There were no acute thromboembolic complications in either group (<24 h post-ablation). CONCLUSIONS: In patients undergoing left atrial catheter ablation for AF or left atrial flutter, use of periprocedural dabigatran etexilate provides a safe and effective anticoagulation strategy compared to warfarin. A prospective randomized study is warranted.

Relation of morbid obesity and female gender to risk of procedural complications in patients undergoing atrial fibrillation ablation.

Obese patients with atrial fibrillation (AF) are frequently treated with AF ablation. We sought to examine whether a body mass index (BMI) threshold exists beyond which the odds of experiencing a complication from AF ablation increases. All patients enrolled in the Vanderbilt AF Registry who underwent catheter-based AF ablation from May 1999 to February 2012 were included. Major complications were recorded. Morbid obesity was defined as a BMI >40 kg/m(2) and examined in multivariable analysis. A total of 35 complications (6.8%) occurred in 512 ablations. Morbidly obese patients experienced a greater rate of complications (6 of 42, 14.3%) than the nonmorbidly obese (29 of 470, 6.2%; p = 0.046). Using a discrete BMI cutoff, the odds of complications increased 3.1-fold in those with morbid obesity (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.1 to 8.4, p = 0.03) and 2.1-fold for female gender (OR 2.1, 95% CI 1.04 to 4.38, p = 0.04). With BMI as a continuous variable, the odds of complications increased by 5% per 1 unit increase in BMI (OR 1.05, 95% CI 1.0 to 1.11, p = 0.05), and the increase for female gender was 2.2-fold (OR 2.2, 95% CI 1.1 to 4.6, p = 0.03). In conclusion, morbid obesity represents a BMI threshold above which the odds of complications with AF ablation increase significantly. The increase in complications appears to be driven primarily by events in women, suggesting that morbidly obese women are a special population when considering AF ablation.

Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation.

BACKGROUND: Common single nucleotide polymorphisms at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical atrial fibrillation (AF). Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5%-30% of AF cases. OBJECTIVE: To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. METHODS: Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years; 71% men; 89% typical AF) between 2004 and 2011. The primary end point was time to recurrence of any nonsinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF). RESULTS: Two-hundred atrial tachycardia, atrial flutter, or AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76; 95% confidence interval [CI] 0.6-0.95; P = .016) compared with wild type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio 0.79; 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio 0.61; 95% CI 0.37-1.0; P = .037). CONCLUSIONS: Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of patients with predominately typical AF. Our findings suggest that the rs2200733 polymorphism may hold promise as an objectively measured patient characteristic that can be used as a clinical tool for selecting patients for AF ablation.

Dabigatran in clinical practice.

BACKGROUND: Stroke and systemic thromboembolism remain critical causes of mortality and morbidity in patients with paroxysmal or persistent atrial fibrillation. Dabigatran etexilate is a novel oral direct thrombin inhibitor, which provides stroke risk reduction for patients with nonvalvular atrial fibrillation. Randomized clinical data demonstrate dabigatran to be an alternative oral anticoagulant with an improved efficacy profile compared with oral warfarin dose adjusted to an INR (international normalized ratio) target of 2.0 to 3.0. OBJECTIVES: Our aim was to review the pharmacology, mechanism of action, drug metabolism, and clinical trial data supporting dabigatran use. METHODS: We reviewed all the major published clinical studies of dabigatran and analyzed data regarding practical applications in selected clinical scenarios. RESULTS: This review provides recommendations for clinicians regarding dosing during invasive surgical procedures, transitioning off alternative anticoagulants, and a discussion of storage and handling of the drug. CONCLUSIONS: Our effort should facilitate the safe and effective use of dabigatran in atrial fibrillation.