Atrial fibrillation (AF) affects over 33 million individuals worldwide1 and has a complex heritability.2 We conducted the largest meta-analysis of genome-wide association studies for AF to date, consisting of over half a million individuals including 65,446 with AF. In total, we identified 97 loci significantly associated with AF including 67 of which were novel in a combined-ancestry analysis, and 3 in a European specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait loci (eQTL) analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

BACKGROUND Patients who have pacemakers or defibrillators are often denied the opportunity to undergo magnetic resonance imaging (MRI) because of safety concerns, unless the devices meet certain criteria specified by the Food and Drug Administration (termed “MRI-conditional” devices). METHODS We performed a prospective, nonrandomized study to assess the safety of MRI at a magnetic field strength of 1.5 Tesla in 1509 patients who had a pacemaker (58%) or an implantable cardioverter–defibrillator (42%) that was not considered to be MRI-conditional (termed a “legacy” device). Overall, the patients underwent 2103 thoracic and nonthoracic MRI examinations that were deemed to be clinically necessary. The pacing mode was changed to asynchronous mode for pacing-dependent patients and to demand mode for other patients. Tachyarrhythmia functions were disabled. Outcome assessments included adverse events and changes in the variables that indicate lead and generator function and interaction with surrounding tissue (device parameters). RESULTS No long-term clinically significant adverse events were reported. In nine MRI examinations (0.4%; 95% confidence interval, 0.2 to 0.7), the patient’s device reset to a backup mode. The reset was transient in eight of the nine examinations. In one case, a pacemaker with less than 1 month left of battery life reset to ventricular inhibited pacing and could not be reprogrammed; the device was subsequently replaced. The most common notable change in device parameters (>50% change from baseline) immediately after MRI was a decrease in P-wave amplitude, which occurred in 1% of the patients. At long-term follow-up (results of which were available for 63% of the patients), the most common notable changes from baseline were decreases in P-wave amplitude (in 4% of the patients), increases in atrial capture threshold (4%), increases in right ventricular capture threshold (4%), and increases in left ventricular capture threshold (3%). The observed changes in lead parameters were not clinically significant and did not require device revision or reprogramming. CONCLUSIONS We evaluated the safety of MRI, performed with the use of a prespecified safety protocol, in 1509 patients who had a legacy pacemaker or a legacy implantable cardioverter– defibrillator system. No long-term clinically significant adverse events were reported. (Funded by Johns Hopkins University and the National Institutes of Health; ClinicalTrials.gov number, NCT01130896.)

BACKGROUND Left atrial flutter (LAFL) occurs in patients after atrial fibrillation ablation. Identification of optimal ablation targets to terminate LAFL remains challenging. OBJECTIVE The purpose of this study was to use patient-specific models to simulate LAFL and predict optimal ablation targets using a novel approach based on flow network theory. METHODS Late gadolinium-enhanced cardiac magnetic resonance scans from 10 patients with LAFL were used to construct atrial models incorporating fibrosis by investigators blinded to procedural findings. Rapid pacing was applied in silico to induce LAFL. In each LAFL, we represented reentrant wave propagation as an electric flow network and identified the “minimum cut” (MC), which was the smallest amount of tissue that separated the flow into 2 discontinuous components. In silico ablation was applied at MCs, and targets were compared to those that terminated LAFL during catheter ablation. RESULTS Patient-specific atrial models were successfully generated from patient scans. LAFL was induced in 7 of 10 models. Ablation of MCs terminated LAFL in 4 models and produced new, slower LAFL morphologies in the other 3. For the latter cases, flow analysis was repeated to identify MCs of emergent LAFLs. Ablation of these MCs terminated emergent LAFLs. The MC-based ablation lesions in simulations were similar in length and location to ablation targets that terminated LAFL during catheter ablation for these 7 patients. CONCLUSION Personalized atrial simulations can predict ablation targets for LAFL. These simulations provide a powerful tool for planning ablation procedures and may reduce procedural times and complications.

Objectives We sought to a) use a novel method of late gadolinium enhancement (LGE) quantification that utilizes normalized intensity measures to confirm the association between LGE extent and atrial fibrillation (AF) recurrence following ablation, and b) examine the presence of interaction and effect modification between LGE and AF persistence. Background Recurrent AF after catheter ablation has been reported to associate with the baseline extent of left atrial (LA) LGE on cardiac magnetic resonance (CMR). Traditional methods for measurement of intensity lack an objective threshold for quantification and interpatient comparisons of LGE. Methods The cohort included 165 participants (60.0±10.2 years, 77% men, 57% persistent AF) that underwent initial AF ablation. The association of baseline LGE extent with AF recurrence was examined using multivariable Cox proportional hazard models. Multiplicative and additive interaction between AF type and LGE extent were examined. Results During 10.2±5.7 months of follow-up, 63 (38.2%) patients experienced AF recurrence. Baseline LGE extent was independently associated with AF recurrence after adjusting for confounders [hazard ratio (HR) 1.5 per 10% increased LGE, P<0.001]. The HR for AF recurrence progressively increased as a function of LGE. The magnitude of association between LGE >35% and AF recurrence was greater among patients with persistent AF (HR 6.5, P=0.001 versus HR 3.6, P=0.001); however, there was no evidence for statistical interaction. Conclusions Regardless of AF persistence at baseline, participants with LGE ≤ 35% have a favorable outcome, whereas those with LGE > 35% have a higher rate of AF recurrence in the first year after ablation. These findings suggest a role for a) patient selection for AF ablation using LGE extent, and b) substrate modification in addition to pulmonary vein isolation in patients with LGE extent exceeding 35% of LA myocardium.

Background Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation (AF). Methods and Results LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients prior to pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio (IIR) defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and IIR in the left atrium (mean ± standard deviation) were 0.98±0.46 m/sec and 0.95±0.26, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local IIR (0.20 m/sec decrease in conduction velocity per increase in unit IIR, P<0.001). Conclusions In this clinical in vivo study we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias.

We developed a fully automatic method for LA and PV segmentation from LGE-MRI, with comparable performance to a human observer. Inclusion of an MRA sequence further improves the segmentation accuracy. The method leads to automatic generation of a patient-specific model, and potentially enables objective atrial scar assessment for AF patients. J. Magn. Reson. Imaging 2016;44:346-354.

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Patient characteristics reflected in CHA2DS2VASc scoring and early institutional experience predict increased complication rates following AF ablation. Despite more patients with higher CHA2DS2VASc scores undergoing AF ablation, complication rates fell over time as institutional experience increased.