Incidence of new-onset atrial fibrillation after transcatheter patent foramen ovale closure using 15 years of Ontario administrative health data.

BACKGROUND: Individuals with patent foramen ovale (PFO) routinely undergo transcatheter closure (TC) for secondary prevention of recurrent stroke. However, some evidence suggests that TC may increase the risk of new-onset atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the risk of new-onset AF following PFO closure and to explore predictors of AF development. METHODS: We created a retrospective cohort of all Ontarians over 18 years of age who received TC between October 2002 and December 2017 using administrative health data and the CorHealth cardiac registry. Poisson regression determined event rates of AF and secondary outcomes such as stroke and mortality per 1000 person-years. A multivariable Cox proportional hazards model identified predictors of new-onset AF following TC. RESULTS: Of 1533 patients, 96 (6.26%) developed new-onset AF following PFO closure, over average follow-up time of 8.2 years. Age >60 years (hazard ratio [HR] 2.82; 95% confidence interval [CI] 1.76-4.51; P <.001) and diabetes (HR 2.49; 95% CI 1.48-4.18; P <.001) were statistically significant, independent predictors of AF according to the Cox model. CONCLUSIONS: The incidence of new-onset AF after PFO closure was relatively low. Having diabetes and age >60 years were the most important factors associated with new-onset AF in this population.

Association of Cardiology Billing Amounts With Health Care Utilization and Clinical Outcomes in Patients With Atrial Fibrillation.

Background The relationship between health care utilization and outcomes in patients with atrial fibrillation is unknown. The objective of this study was to investigate whether cardiologists' billing amounts in a fee-for-service environment are associated with better patient-level clinical outcomes. Methods and Results A retrospective cohort study was conducted using administrative claims data of cardiologists in Ontario, Canada between April 1, 2011 and March 31, 2016. The cardiologists were stratified into quintiles based on their median billing patterns per patient over the observation period. The primary outcomes were patient-level receipt of repeat visits, cardiac diagnostic tests, and medications ≤1 year of index date. The secondary clinical outcomes were death, emergency department visits, and all-cause hospitalization 1-year post-index visit. The patient cohort comprised 182 572 patients with atrial fibrillation (median age 74 years, 58% male) from 467 cardiologists. Patients with atrial fibrillation seen by higher-billing cardiologists were 26% more likely to have an echocardiogram (adjusted odds ratio [aOR], 1.26 [95% CI, 1.10-1.43] for quintile 5 versus 2), 28% a stress test (aOR, 1.28 [1.12-1.46] for quintile 5 versus 2), 25% continuous electrocardiographic monitoring (aOR, 1.25 [1.08-1.46] for quintile 4 versus 2), and 79% more likely to get a stress echocardiogram (aOR, 1.79 [1.32-2.42] for quintile 5 versus 2). They also had a higher rate of all-cause hospitalization (aOR, 1.13 [1.07-1.20]). Mortality rates were similar across cardiologists billing quintiles (eg, aOR, 0.98 [0.87-1.11] for quintile 4 versus 2). Conclusions Higher-billing cardiologists ordered more diagnostic tests per patient with atrial fibrillation but these are not associated with improvements in outcomes.

Heparin for Vertebral Intraluminal Thrombus Causing Retroperitoneal Hemorrhage from Occult Renal Angiomyolipoma.

Stroke is a common cause of mortality and serious long-term disability worldwide. In the acute setting, current American Heart Association/American Stroke Association guidelines do not recommend routine anticoagulation for the management of acute ischemic strokes. However, short-term use of unfractionated heparin (UFH) in select subpopulations has demonstrated improved outcomes. While tools such as CHADSVASC and HASBLED scores are useful in stratifying risk of long-term anticoagulation in patients with nonvalvular atrial fibrillation and additional risk factors, the carefully selected patient populations for the design of these studies do not account for risk of hemorrhage from other preexisting conditions. Here, we present a patient with a posterior circulation intraluminal thrombus treated with UFH, who manifested with a near-fatal intra-abdominal hemorrhage from a previously undetected renal angiomyolipoma (AML).

Longitudinal Measures of Blood Pressure and Subclinical Atrial Arrhythmias: The MESA and the ARIC Study.

Background High blood pressure (BP) is a well-known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi-Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000-2018 in MESA and 1987-2017 in ARIC study), we calculated individual long-term mean, trend, and detrended visit-to-visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance-weighted meta-analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit-to-visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02-1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01-1.15). For pulse pressure as well, higher visit-to-visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00-1.37). In addition, higher long-term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08-1.70). Conclusions Antecedent visit-to-visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

Autonomic Alterations After Pulmonary Vein Isolation in the CIRCA-DOSE (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation) Study.

Background The natural history of autonomic alterations following catheter ablation of drug-refractory paroxysmal atrial fibrillation is poorly defined, largely because of the historical reliance on non-invasive intermittent rhythm monitoring for outcome ascertainment. Methods and Results The study included 346 patients with drug-refractory paroxysmal atrial fibrillation undergoing pulmonary vein isolation using contemporary advanced-generation ablation technologies. All patients underwent insertion of a Reveal LINQ (Medtronic) implantable cardiac monitor before ablation. The implantable cardiac monitor continuously recorded physical activity, heart rate variability (measured as the SD of the average normal-to-normal), daytime heart rate, and nighttime heart rate. Longitudinal autonomic data in the 2-month period leading up to the date of ablation were compared with the period from 91 to 365 days following ablation. Following ablation there was a significant decrease in SD of the average normal-to-normal (mean difference versus baseline of 19.3 ms; range, 12.9-25.7; P<0.0001), and significant increases in daytime and nighttime heart rates (mean difference versus baseline of 9.6 bpm; range, 7.4-11.8; P<0.0001, and 7.4 bpm; range, 5.4-9.3; P<0.0001, respectively). Patients free of arrhythmia recurrence had significantly faster daytime (11±11 versus 8±12 bpm, P=0.001) and nighttime heart rates (8±9 versus 6±8 bpm, P=0.049), but no difference in SD of the average normal-to-normal (P=0.09) compared with those with atrial fibrillation recurrence. Ablation technology and cryoablation duration did not influence these autonomic nervous system effects. Conclusions Pulmonary vein isolation results in significant sustained changes in the heart rate parameters related to autonomic function. These changes are correlated with procedural outcome and are independent of the ablation technology used. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01913522.

New-onset atrial fibrillation following percutaneous closure of patent foramen ovale: a systematic review and meta-analysis.

PURPOSE: A patent foramen ovale (PFO), present in up to 25% of adults, is an embryologic remnant which allows for right to left shunting and has been implicated in cryptogenic stroke (Neill and Lin, Methodist Debakey Cardiovasc J. 13(3):152-159, 2017; Bass 2015). The current standard of care for selected patients with PFO and cryptogenic stroke is transcatheter closure, but the risk of post-closure, new-onset atrial fibrillation (AF) is unknown (Vaidya et al., Cardiovasc Diagn Ther. 8(6):739-753, 2018; Kjeld et al., Acta Radiol Open. 7(9):2058460118793922, 2018; Staubach et al., Catheter Cardiovasc Interv. 74(6):889-95, 2009). This systematic review and meta-analysis synthesized evidence on AF development post transcatheter PFO closure and predictors of AF development, and assessed existing knowledge gaps. METHODS: Randomized controlled trials and observational studies were selected according to the inclusion criteria of adults that underwent a transcatheter PFO closure without a history of AF. Studies were retrieved from electronic databases from inception until February 2019. A Freeman-Tukey arcsine transformation was performed for meta-analysis of AF incidence rate. RESULTS: From 765 studies, 45 were included in quantitative data synthesis. Study sample sizes ranged between 20 and 1887 individuals, and average patient age between 37 to 67 years across studies. The overall incidence rate was 0.013 person-years, and 0.014 person-years for the within 6 months follow-up subgroup. There was no consistency in reported predictors of AF development. CONCLUSIONS: The incidence of AF post-PFO closure was low across studies, with a high level of between-study heterogeneity. Until a concerted effort is made to improve accurate AF diagnosis, it will be difficult to gauge the association between transcatheter PFO closure and incidence of AF.

Use and Outcomes Associated With Perioperative Amiodarone in Cardiac Surgery.

Background In randomized controlled trials, perioperative administration of amiodarone has been shown to reduce the incidence of postoperative atrial arrhythmias and length of stay (LOS) among patients undergoing coronary bypass surgery. However, little is known about the use or effectiveness of perioperative amiodarone in routine clinical practice. Methods and Results We studied patients ≥18 years old without a previous history of atrial or ventricular arrhythmias who underwent elective coronary bypass surgery between 2013 and 2014 within a network of 235 US hospitals. Perioperative amiodarone was defined as receipt of amiodarone either on the day of or the day preceding surgery. We used covariate-adjusted modeling and instrumental variable methods to examine the association between receipt of amiodarone and the development of atrial arrhythmias, in-hospital mortality, readmission, LOS, and cost. Of 12 758 patients, 2195 (17.2%) received perioperative amiodarone, 3330 (26.1%) developed atrial arrhythmias postoperatively, and the average LOS was 6.4 days (±2.6 days). Instrumental variable analysis showed that receipt of perioperative amiodarone was associated with lower risk of atrial arrhythmias (risk difference -11 percentage points, 95% CI -19 to -4 percentage points; P=0.002) and a shorter LOS (-0.7 day, 95% CI -1.39 to -0.01 days; P=0.048). There was no association between receipt of perioperative amiodarone and in-hospital mortality, cost, or readmission. Conclusions Among patients undergoing coronary bypass surgery without previous arrhythmias, perioperative amiodarone is associated with a lower risk of atrial arrhythmias and shorter LOS. These findings are consistent with previous randomized trials and lend support to current guideline recommendations.

NT -pro BNP as a Mediator of the Racial Difference in Incident Atrial Fibrillation and Heart Failure.

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation ( AF ). Conversely, whites may have a lower risk of heart failure ( CHF ). N-terminal pro-B-type natriuretic peptide ( NT -pro BNP) levels are higher in whites, predict incident AF , and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT -pro BNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT -pro BNP . The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT -pro BNP ( CHS : 40% higher than blacks; 95% CI , 29-53; ARIC : 39% higher; 95% CI , 33-46) and had a greater risk of incident AF compared with blacks ( CHS : adjusted hazard ratio, 1.60; 95% CI , 1.31-1.93; ARIC : hazard ratio, 1.93; 95% CI , 1.57-2.27). NT -pro BNP levels explained a significant proportion of the racial difference in AF risk ( CHS : 36.2%; 95% CI , 23.2-69.2%; ARIC : 24.6%; 95% CI , 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI , 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI , 0.94-1.23), CHF -related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT -pro BNP levels. No consistent relationship between race and CHF was observed.

Liver Disease as a Predictor of New-Onset Atrial Fibrillation.

Background Impact of liver disease on development of atrial fibrillation ( AF ) is unclear. The purpose of the study was to evaluate prevalence of AF in the setting of liver disease and whether increasing severity of liver disease, using Model for End-Stage Liver Disease ( MELD ), is independently associated with increased risk of AF . Methods and Results Retrospective data analysis of 1727 patients with liver disease evaluated for liver transplantation between 2006 and 2015 was performed, and patient characteristics were analyzed from billing codes and review of medical records. Multivariable time-dependent Cox proportional hazards model was performed to determine effect of increasing MELD score on risk of developing AF . Prevalence of AF was 11.2%. Incidence of AF at median follow-up time of 1.04 years was 8.5%. Both prevalence and incidence of AF increased with increasing MELD scores. Prevalence of AF was 3.7%, 6.4%, 16.7%, and 20.2% corresponding with MELD quartiles 1 to 10, 11 to 20, 21 to 30, and >30, respectively. Compared with patients with MELD quartile 1 to 10, patients with MELD quartile of 11 to 20 had hazard ratio of 2.73 (confidence interval, 1.47-5.07), those in the MELD quartile of 21 to 30 had a hazard ratio of 5.17 (confidence interval, 2.65-10.09), and those with MELD values >30 had hazard ratio of 9.33 (confidence interval, 3.93-22.14) for development of new-onset AF . Other significant variables associated with new-onset AF were age, sleep apnea, valvular heart disease, hemodynamic instability, and reduced left ventricular ejection fraction <50% (hazard ratio, of 1.06, 2.17, 3.21, 2.00, and 2.44, respectively). Conclusions Prevalence and incidence of AF in patients with liver disease is high. Severity of liver disease, as measured by MELD , is an important predictor of new-onset AF . This novel finding suggests an interaction between inflammatory and neurohormonal changes in liver disease and pathogenesis of AF .

Safety and Efficacy of Novel Oral Anticoagulants Versus Warfarin in Medicare Beneficiaries With Atrial Fibrillation and Valvular Heart Disease.

BACKGROUND: We examined a large community-based sample of patients with atrial fibrillation (AF) and valvular heart disease (VHD) (excluding prosthetic valves) with a goal to compare outcomes among patients with AF, with and without VHD, taking warfarin, dabigatran, and rivaroxaban. METHODS AND RESULTS: We identified Medicare beneficiaries enrolled in Medicare Part D benefit plan from 2011 to 2013 with newly diagnosed AF (18 137 patients with VHD [dabigatran, 1979; rivaroxaban, 2027; warfarin, 14 131] and 85 596 patients without VHD [dabigatran, 13 522; rivaroxaban, 14 257; warfarin, 57 817]). Primary outcomes of all-cause mortality, ischemic strokes, major bleeding, and myocardial infarction were compared across the 3 anticoagulants using 3-way propensity-matched samples. After propensity matching, a total of 5871 patients with VHD and 40 221 patients without VHD and AF were studied. Both dabigatran and rivaroxaban were associated with significantly lower risk of death in patients with VHD with AF (dabigatran versus warfarin: hazard ratio, 0.71; 95% confidence interval, 0.52-0.98; P=0.038; rivaroxaban versus warfarin: hazard ratio, 0.68; 95% confidence interval, 0.49-0.95; P=0.022). Nongastrointestinal bleeding was significantly reduced with dabigatran and rivaroxaban versus warfarin in those with VHD (dabigatran versus warfarin: hazard ratio, 0.17; 95% confidence interval, 0.06-0.49; P=0.001; rivaroxaban versus warfarin: hazard ratio, 0.37; 95% confidence interval, 0.17-0.84; P=0.017). Ischemic stroke and gastrointestinal bleeding rates did not differ between rivaroxaban, dabigatran, and warfarin in patients with VHD. The effects of the 3 anticoagulants on outcomes were comparable in patients with and without VHD and with AF. CONCLUSIONS: In this cohort of Medicare beneficiaries with VHD (excluding patients with prosthetic valves) and new-onset AF between 2011 and 2013, novel oral non-vitamin K anticoagulants were safe and effective options for prevention of systemic thromboembolism.

Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial.

BACKGROUND: Atrial fibrillation (AF) can be a cause of previously diagnosed cryptogenic stroke. However, AF can be paroxysmal and asymptomatic, thereby making detection with routine ECG methods difficult. Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF, but its initiation is dependent on the detection of AF. Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) is the first randomized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors (ICM). METHODS AND RESULTS: Patients with prior cryptogenic stroke were randomized to control (n=220) or ICM (n=221) and followed for ≤36 months. Cumulative AF detection rates in the ICM arm increased progressively during this period (3.7%, 8.9%, 12.4%, and 30.0% at 1, 6, 12, and 36 months, respectively), but remained low in the control arm (3.0% at 36 months). This resulted in oral anticoagulation prescription in 94.7% of ICM patients with AF detected at 6 months, 96.6% at 12 months, and 90.5% at 36 months. Among ICM patients with AF detected, the median time to AF detection was 8.4 months, 81.0% of first AF episodes were asymptomatic, and 94.9% had at least 1 day with >6 minutes of AF. CONCLUSIONS: Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care. Given the frequency of asymptomatic first episodes and the long median time to detection, these findings highlight the limitations of using traditional AF detection methods. The majority of patients with AF were prescribed oral anticoagulation therapy. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov; Unique identifier: NCT00924638.

Common and rare variants in SCN10A modulate the risk of atrial fibrillation.

BACKGROUND: Genome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541 is in high linkage disequilibrium with the nonsynonymous variant in SCN10A, rs6795970 (V1073A, r(2)=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. METHODS AND RESULTS: SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1.35 [1.16-1.54]; P=2.3×10(-5)). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function. CONCLUSIONS: The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF.

Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence.

BACKGROUND: Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures. METHODS AND RESULTS: Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in nicotinamide adenine dinucleotide (NADH) fluorescence, leading to a 60% to 70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (r=0.89, P<0.001). At physiological temperatures, loss of NADH became visually apparent within 26±8 s after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (r=0.84±0.06, P<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum, which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites. CONCLUSIONS: We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination.

Incidence and significance of early recurrences of atrial fibrillation after cryoballoon ablation: insights from the multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial.

BACKGROUND: Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. METHODS AND RESULTS: The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03-4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82-8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01-0.32; P=0.002). CONCLUSIONS: ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Candidate gene approach to identifying rare genetic variants associated with lone atrial fibrillation.

BACKGROUND: Rare variants in candidate atrial fibrillation (AF) genes have been associated with AF in small kindreds. The extent to which such polymorphisms contribute to AF is unknown. OBJECTIVE: The purpose of this study was to determine the spectrum and prevalence of rare amino acid coding (AAC) variants in candidate AF genes in a large cohort of unrelated lone AF probands. METHODS: We resequenced 45 candidate genes in 303 European American (EA) lone AF probands (186 lone AF probands screened for each gene on average [range 89-303], 63 screened for all) identified in the Vanderbilt AF Registry (2002-2012). Variants detected were screened against 4300 EAs from the Exome Sequencing Project (ESP) to identify very rare (minor allele frequency ≤0.04%) AAC variants and these were tested for AF co-segregation in affected family members where possible. RESULTS: Median age at AF onset was 46.0 years [interquartile range 33.0-54.0], and 35.6% had a family history of AF. Overall, 63 very rare AAC variants were identified in 60 of 303 lone AF probands, and 10 of 19 (52.6%) had evidence of co-segregation with AF. Among the 63 lone AF probands who had 45 genes screened, the very rare variant burden was 22%. Compared with the 4300 EA ESP, the proportion of lone AF probands with a very rare AAC variant in CASQ2 and NKX2-5 was increased 3-5-fold (P <.05). CONCLUSION: No very rare AAC variants were identified in ~80% of lone AF probands. Potential reasons for the lack of very rare AAC variants include a complex pattern of inheritance, variants in as yet unidentified AF genes or in noncoding regions, and environmental factors.

Pulmonary vein isolation using a pace-capture-guided versus an adenosine-guided approach: effect on dormant conduction and long-term freedom from recurrent atrial fibrillation--a prospective study.

BACKGROUND: Atrial fibrillation recurrence after pulmonary vein (PV) isolation is associated with PV to left atrium reconduction. We prospectively studied the use of 2 procedural techniques designed to facilitate identification of residual gaps within the index ablation line. METHODS AND RESULTS: After wide circumferential PV isolation, 40 patients received additional ablation targeted at locations of left atrial capture during high-output pacing (pace-capture group), while 40 patients underwent adenosine testing with targeted ablation at sites of dormant conduction (adenosine group). Patients were followed up at 3, 6, and 12 months. After PV isolation, high-output pace-capture was documented in 39 PVs (25%; 50% of patients) in the pace-capture group. Dormant conduction was unmasked in 34 PVs (22%; 53% of patients) in the adenosine group. A subset of 25 patients in the pace-capture group underwent adenosine testing without targeted ablation of dormant conduction. In these patients, only 10 out of 86 PVs (11.6%; 24% of patients) demonstrated dormant conduction after the elimination of local pace-capture. At a follow-up of 329±124 days, the single procedure off antiarrhythmic drug freedom from recurrent atrial fibrillation was 67.5% in the adenosine group and 65.0% in the pace-capture group (P=0.814). Procedure duration and fluoroscopy time were significantly longer in the pace-capture group (P=0.002 and P<0.001), whereas radiofrequency ablation time was comparable (P=0.192). CONCLUSIONS: The use of high-output pacing post-PV isolation results in a significant reduction in the incidence of dormant conduction with a comparable long-term freedom from recurrent atrial fibrillation (versus adenosine-guided ablation). The use of these approaches requires evaluation in a long-term prospective randomized study. [corrected].