Noninvasive localization of cardiac arrhythmias using electromechanical wave imaging.

Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. The 12-lead electrocardiogram (ECG) is the current noninvasive clinical tool used to diagnose and localize cardiac arrhythmias. However, it has limited accuracy and is subject to operator bias. Here, we present electromechanical wave imaging (EWI), a high-frame rate ultrasound technique that can noninvasively map with high accuracy the electromechanical activation of atrial and ventricular arrhythmias in adult patients. This study evaluates the accuracy of EWI for localization of various arrhythmias in all four chambers of the heart before catheter ablation. Fifty-five patients with an accessory pathway (AP) with Wolff-Parkinson-White (WPW) syndrome, premature ventricular complexes (PVCs), atrial tachycardia (AT), or atrial flutter (AFL) underwent transthoracic EWI and 12-lead ECG. Three-dimensional (3D) rendered EWI isochrones and 12-lead ECG predictions by six electrophysiologists were applied to a standardized segmented cardiac model and subsequently compared to the region of successful ablation on 3D electroanatomical maps generated by invasive catheter mapping. There was significant interobserver variability among 12-lead ECG reads by expert electrophysiologists. EWI correctly predicted 96% of arrhythmia locations as compared with 71% for 12-lead ECG analyses [unadjusted for arrhythmia type: odds ratio (OR), 11.8; 95% confidence interval (CI), 2.2 to 63.2; P = 0.004; adjusted for arrhythmia type: OR, 12.1; 95% CI, 2.3 to 63.2; P = 0.003]. This double-blinded clinical study demonstrates that EWI can localize atrial and ventricular arrhythmias including WPW, PVC, AT, and AFL. EWI when used with ECG may allow for improved treatment for patients with arrhythmias.

Relation of Electrocardiographic Left Atrial Abnormalities to Risk of Stroke in Patients with Atrial Fibrillation.

The P-wave terminal force in lead V1 (PTFV1) on the 12-lead electrocardiogram (ECG) quantifies left atrial (LA) structural and electrophysiologic abnormalities. We aimed to evaluate the association between PTFV1 and cerebrovascular accident (CVA) as well as LA structure and function in patients with atrial fibrillation (AF). We conducted a cross-sectional study of 229 patients with AF (60 ± 10years, 72% men) with (n = 21) and without (n = 208) a history of CVA, who underwent preablation ECG and cardiac magnetic resonance in sinus rhythm. PTFV1 was defined as the duration (in milliseconds) of the downward deflection of the P wave in lead V1 multiplied by the absolute value of its amplitude (in microvolts) on ECG. PTFV1 is associated with LA minimum volume (Vmin) and left ventricular ejection fraction but not associated with the extent of LA fibrosis quantified by cardiac magnetic resonance late gadolinium enhancement. In addition, PTFV1 is associated with CVA independent of the CHA2DS2-VASc score and LA Vmin (odds ratio 1.23; 95% confidence interval 1.08 to 1.40; p = 0.002). Furthermore, PTFV1 has an incremental value over the CHA2DS2-VASc score as a marker of CVA (p <0.001). In conclusion, ECG-defined PTFV1 is independent marker of stroke in patients with AF and reflects the underlying LA remodeling. Our findings suggest that evaluation of PTFV1 can improve the current risk stratification of stroke.

Association Between Left Atrial Stiffness Index and Atrial Fibrillation Recurrence in Patients Undergoing Left Atrial Ablation.

BACKGROUND: Atrial fibrillation (AF) is associated with significant abnormalities of left atrial (LA) systolic and diastolic function. This study describes a novel measure, LA stiffness index, that estimates LA diastolic function and its association with clinical outcomes of catheter ablation. METHODS AND RESULTS: A total of 219 AF patients referred for ablation (59% paroxysmal, mean CHA2DS2VASc score 1.7 ± 1.4) were enrolled. Atrial pressure and volume loops were prepared from invasive pressure measures and cardiac magnetic resonance imaging volumetric data during sinus rhythm for all patients. An LA stiffness index was created, defined by the ratio of change in LA pressure to volume during passive filling of LA (ΔP/ΔV). Patients were followed prospectively. Mean LA stiffness index for AF patients was 0.6 ± 0.5 mm Hg/mL (paroxysmal AF 0.51 ± 0.4 and persistent AF 0.73 ± 0.6; P < 0.001). Linear regression analysis showed a rise in the stiffness index with age, increasing at a rate of 0.02 mm Hg/mL per year (P < 0.001). The LA stiffness index was higher in patients with previous LA ablation(s) for AF (0.51 ± 0.35 versus 0.83 ± 0.70; P < 0.001). Forty of 160 patients had recurrence after AF ablation with a mean follow-up of 10.4 ± 7.6 months. Patients with recurrence had higher stiffness index than those without recurrence (0.83 ± 0.46 versus 0.40 ± 0.22; P < 0.001). CONCLUSIONS: LA stiffness index, a novel measure to assess LA diastolic function, increases with age and is higher in persistent AF and in the setting of repeat AF ablation. Greater LA stiffness index was independently associated with recurrence of AF after LA ablation.

Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

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. METHODS AND RESULTS: LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before 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 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 image intensity ratio in the left atrium (mean ± SD) were 0.98 ± 0.46 and 0.95 ± 0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, 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.

Left Atrial LGE and Arrhythmia Recurrence Following Pulmonary Vein Isolation for Paroxysmal and Persistent AF.

OBJECTIVES: The aims of this study were to: 1) use a novel method of late gadolinium enhancement (LGE) quantification that uses normalized intensity measures to confirm the association between LGE extent and atrial fibrillation (AF) recurrence following ablation; and 2) 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 LGE on cardiac magnetic resonance. Traditional methods for measurement of intensity lack an objective threshold for quantification and interpatient comparisons of LGE. METHODS: The cohort included 165 participants (mean age 60.0 ± 10.2 years, 77% men, 57% with persistent AF) who underwent initial AF ablation. The association of baseline LGE extent with AF recurrence was examined using multivariable Cox proportional hazards models. Multiplicative and additive interactions between AF type and LGE extent were examined. RESULTS: During 10.2 ± 5.7 months of follow-up, 63 patients (38.2%) experienced AF recurrence. Baseline LGE extent was independently associated with AF recurrence after adjusting for confounders (hazard ratio: 1.5 per 10% increased LGE; p < 0.001). The hazard ratio 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 (hazard ratio: 6.5 [p = 0.001] vs. 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 favorable outcomes, whereas those with LGE >35% have a higher rate of AF recurrence in the first year after ablation. These findings suggest a role for: 1) patient selection for AF ablation using LGE extent; and 2) substrate modification in addition to pulmonary vein isolation in patients with LGE extent exceeding 35% of left atrial myocardium.

Prevalence, Patterns, and Clinical Predictors of Left Ventricular Late Gadolinium Enhancement in Patients Undergoing Cardiac Magnetic Resonance Prior to Pulmonary Vein Antral Isolation for Atrial Fibrillation: A Cross-Sectional Observational Study.

Cardiac magnetic resonance (CMR) imaging is increasingly used to evaluate patients with atrial fibrillation (AF) before pulmonary vein antral isolation (PVAI). The purpose of this study was to assess the incidence and pattern of left ventricular (LV) late gadolinium enhancement (LGE) in patients undergoing CMR before PVAI and compare the clinical and demographic differences of patients with and without LV LGE. Clinical and demographic data on 62 patients (mean age 61 ±â€Š7.9, 69% male) undergoing CMR before PVAI for AF were collected. Two observers, masked to clinical histories, independently recorded the prevalence, extent (number of myocardial segments), and pattern (subendocardial, midmyocardial, or subepicardial) of LV LGE in each patient. Clinical and demographic predictors of LV LGE were determined using logistic regression. Twenty-three patients (37%) demonstrated LV LGE affecting a mean of 3.0 ±â€Š2.1 myocardial segments. There was no difference in LV ejection fraction between patients with and without LGE, and most (65%) patients with LGE had normal wall motion. Only age (P = 0.04) and a history of congestive heart failure (P = .03) were statistically significant independent predictors of LGE. The most common LGE pattern was midmyocardial, seen in 17 of 23 (74%) patients. Only 4 of 23 (17%) patients had LGE in an "expected" pattern based on clinical history. Of the remaining 19 patients, 4 had known congestive heart failure, 5 nonischemic cardiomyopathy, 4 known coronary artery disease, and 2 prior aortic valve replacement. Six of 23 (26%) patients had no known coronary artery, valvular, or myocardial disease. There is a high prevalence of unexpected LV scar in patients undergoing CMR before PVAI for AF, with most patients demonstrating a nonischemic pattern of LV LGE and no wall motion abnormalities (ie, subclinical disease). The high prevalence of unexpected LGE in these patients may argue for CMR as the modality of choice for imaging integration before PVAI, especially given the demonstrated prognostic value of LGE in this and other patient populations.

MRI Evaluation of Radiofrequency, Cryothermal, and Laser Left Atrial Lesion Formation in Patients with Atrial Fibrillation.

BACKGROUND:  Catheter ablation utilizing radiofrequency (RF), Cryothermal (Cryo), or Laser energy is effective for treatment of atrial fibrillation (AF). Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been used to estimate the burden of left atrial (LA) fibrosis, but no data exist regarding structural changes following each modality. We sought to compare the baseline to postprocedure change in LA scar burden following RF, Cryo, or Laser ablation for treatment of AF. METHODS: Seventeen patients with AF underwent initial pulmonary vein (PV) isolation (PVI) using RF (n = 7), Cryo (n = 5), and Laser (n = 5). LGE-MRI was performed prior to and at 24 hours and 3 months after PVI. RESULTS: In a linear mixed-effects model, accounting for intrapatient clustering of data and interpatient differences in baseline scar, LGE extent was significantly increased at 24 hours postablation (+14.6 ± 1.9% of LA myocardium, P < 0.001), and remained stable from 24 hours to 3 months (+0.12 ± 1.9%, P = 0.951). There was no statistically significant difference between the postablation scar extent among ablation modalities when compared to RF (Cryo +4.5 ± 3.0%, P = 0.123; Laser -3.2 ± 3.0%, P = 0.291). The PV antral LGE intensity was increased by 25.1 ± 3.8% (P<0.001) 24 hours after ablation and additionally increased by 8.1 ± 3.8 at 3 months (P = 0.033). CONCLUSIONS: Radiofrequency, Cryo, and laser ablation result in increased LGE extent and intensity at 24 hours and 3 months postablation. No statistically significant difference was noted in the extent of fibrosis induced by any modality.

Association of common variations on chromosome 4q25 and left atrial volume in patients with atrial fibrillation.

AIMS: Recent studies have shown that several genetic variants near the PITX2 locus on chromosome 4q25 are associated with atrial fibrillation (AF). However, the mechanism that mediates this association remains unclear. Basic murine studies suggest that reduced PITX2 expression is associated with left atrial dilatation. We sought to examine the association between single nucleotide polymorphisms (SNPs) near PITX2 and left atrial size in patients with AF. METHODS: We prospectively enrolled 96 consecutive patients (mean age 60 ± 10 years, 72% male) with drug-resistant AF (57% paroxysmal, 38% persistent, and 5% long-standing persistent) who underwent catheter ablation. Following DNA extraction from blood obtained pre-operatively, SNPs rs10033464 and rs2200733 were genotyped using the Sequenom MassARRAY. Left atrial volume (LAV) was determined using three-dimensional imaging (CT or MRI prior to first ablation) and by investigators blinded to genotype results. RESULTS: The minor allele frequencies at SNPs rs10033464 and rs2200733 were 0.14 and 0.25, respectively. Using multivariable linear regression, homozygosity for the minor allele at rs10033464 (recessive model) was independently associated with larger LAV (P = 0.002) after adjustment for age, gender, BMI, height, type, and duration of AF, left ventricular ejection fraction, history of hypertension, valve disease, and antiarrhythmic drug use. The strength of the association was reconfirmed in a bootstrap study with 1000 resamplings. In contrast, no association was found between rs2200733 variant alleles and LAV. CONCLUSION: SNP rs10033464 near the PITX2 locus on 4q25 is associated with LAV. Left atrial dilatation may mediate the association of common variants at 4q25 with AF.

Quantitative tissue-tracking cardiac magnetic resonance (CMR) of left atrial deformation and the risk of stroke in patients with atrial fibrillation.

BACKGROUND: Recent evidence suggests that left atrial (LA) dysfunction may be mechanistically contributing to cerebrovascular events in patients with atrial fibrillation (AF). We investigated the association between regional LA function and a prior history of stroke during sinus rhythm in patients referred for catheter ablation of AF. METHODS AND RESULTS: A total of 169 patients (59 ± 10 years, 74% male, 29% persistent AF) with a history of AF in sinus rhythm at the time of pre-ablation cardiac magnetic resonance (CMR) were analyzed. The LA volume, emptying fraction, strain (S), and strain rate (SR) were assessed by tissue-tracking cardiac magnetic resonance. The patients with a history of stroke or transient ischemic attack (n=18) had greater LA volumes (Vmax and Vmin; P=0.02 and P<0.001, respectively), lower LA total emptying fraction (P<0.001), lower LA maximum and pre-atrial contraction strains (Smax and SpreA; P<0.001 and P=0.01, respectively), and lower absolute values of LA SR during left ventricular (LV) systole and early diastole (SRs and SRe; P=0.005 and 0.03, respectively) than those without stroke/transient ischemic attack (n=151). Multivariable analysis demonstrated that the LA reservoir function, including total emptying fraction, Smax, and SRs, was associated with stroke/transient ischemic attack (odds ratio 0.94, 0.91, and 0.17; P=0.03, 0.02, and 0.04, respectively) after adjusting for the CHA2DS2-VASc score and LA Vmin. CONCLUSIONS: Depressed LA reservoir function assessed by tissue-tracking cardiac magnetic resonance is significantly associated with a prior history of stroke/transient ischemic attack in patients with AF. Our findings suggest that assessment of LA reservoir function can improve the risk stratification of cerebrovascular events in AF patients.

Association of left atrial function and left atrial enhancement in patients with atrial fibrillation: cardiac magnetic resonance study.

BACKGROUND: Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. METHODS AND RESULTS: LA structure and function was measured in 90 patients with AF (age 61±10 years; 76% men) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain, LA systolic strain rate, and early and late diastolic strain rates were measured using cine-cardiac magnetic resonance images acquired during sinus rhythm. The degree of LGE was quantified. Compared with patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (56±17 versus 49±13 mL/m(2); P=0.036), and increased LGE (27.1±11.7% versus 36.8±14.8%; P<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate) were lower in patients with persistent AF (P<0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared with patients with AF (P<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate (P<0.05 for all). CONCLUSIONS: Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking cardiac magnetic resonance may add important information about the physiological importance of LA fibrosis.

The association of left atrial low-voltage regions on electroanatomic mapping with low attenuation regions on cardiac computed tomography perfusion imaging in patients with atrial fibrillation.

BACKGROUND: Previous studies have shown that contrast-enhanced multidetector computed tomography (CE-MDCT) could identify ventricular fibrosis after myocardial infarction. However, whether CE-MDCT can characterize atrial low-voltage regions remains unknown. OBJECTIVE: The purpose of this study was to examine the association of CE-MDCT image attenuation with left atrial (LA) low bipolar voltage regions in patients undergoing repeat ablation for atrial fibrillation recurrence. METHODS: We enrolled 20 patients undergoing repeat ablation for atrial fibrillation recurrence. All patients underwent preprocedural 3-dimensional CE-MDCT of the LA, followed by voltage mapping (>100 points) of the LA during the ablation procedure. Epicardial and endocardial contours were manually drawn around LA myocardium on multiplanar CE-MDCT axial images. Segmented 3-dimensional images of the LA myocardium were reconstructed. Electroanatomic map points were retrospectively registered to the corresponding CE-MDCT images. RESULTS: A total of 2028 electroanatomic map points obtained in sinus rhythm from the LA endocardium were registered to the segmented LA wall CE-MDCT images. In a linear mixed model, each unit increase in the local image attenuation ratio was associated with 25.2% increase in log bipolar voltage (P = .046) after adjusting for age, sex, body mass index, and LA volume, as well as clustering of data by patient and LA regions. CONCLUSION: We demonstrate that the image attenuation ratio derived from CE-MDCT is associated with LA bipolar voltage. The potential ability to image fibrosis via CE-MDCT may provide a useful alternative in patients with contraindications to magnetic resonance imaging.

Safety of novel oral anticoagulants compared with uninterrupted warfarin for catheter ablation of atrial fibrillation.

BACKGROUND: The novel oral anticoagulants (NOACs) are used for stroke prevention in atrial fibrillation (AF), but their safety and efficacy in the periablation period are not well established. Additionally, no standard procedure for managing periprocedural and intraprocedural anticoagulation has been established. OBJECTIVE: To evaluate the frequency of hemorrhagic and thrombotic events as well as periprocedural management strategies of NOACs compared with warfarin as anticoagulation therapy for AF ablation. METHODS: This was a retrospective cohort study from a prospective AF ablation registry maintained at a large, academic medical center. RESULTS: A total of 374 cases (173 warfarin, 123 dabigatran, 61 rivaroxaban, and 17 apixaban) were included in the analysis. The overall hemorrhagic/thrombotic event rate was 14.2 % (major hemorrhage 2.7%, minor hemorrhage 11.2%, thrombotic stroke 0.5%). The frequency of minor hemorrhage was significantly higher with warfarin compared with dabigatran (15% vs 5.7%, P = 0.012). The average heparin dose required to reach the goal activated clotting time (ACT) was 5600 units for warfarin, 12 900 units for dabigatran (P < 0.001), 15 100 units for rivaroxaban (P < 0.001), and 14 700 units for apixaban (P < 0.001). The average time in minutes to reach the goal ACT was significantly longer, compared with warfarin, for dabigatran (57 vs 28, P < 0.001), rivaroxaban (63 vs 28, P < 0.001), and apixaban (72 vs 28, P < 0.001). CONCLUSIONS: Compared with warfarin, periprocedural anticoagulation with dabigatran resulted in fewer minor hemorrhages and total adverse events after AF ablation. Patients anticoagulated with NOACs required larger doses of heparin and took longer to reach the goal ACT compared with patients anticoagulated with warfarin.

Comparison of preexisting and ablation-induced late gadolinium enhancement on left atrial magnetic resonance imaging.

BACKGROUND: Postablation atrial fibrillation recurrence is positively associated with the extent of preexisting left atrial (LA) late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI), but negatively associated with the extent of postablation LGE regardless of proximity to the pulmonary vein antra. The characteristics of pre- vs postablation LA LGE may provide insight into this seeming paradox and inform future strategies for ablation. OBJECTIVE: The purpose of this study was to define the characteristics of preexisting vs ablation-induced LA LGE. METHODS: LGE-MRI was prospectively performed before and ≥3 months after initial ablation in 20 patients. The intracardiac locations of ablation points were coregistered with the corresponding sites on axial planes of postablation LGE-MRI. The image intensity ratio (IIR), defined as the LA myocardial MRI signal intensity divided by the mean LA blood pool intensity, and LA myocardial wall thickness were calculated on pre- and postablation images. RESULTS: Imaging data from 409 pairs of pre- and postablation axial LGE-MRI planes and 6961 pairs of pre- and postablation image sectors were analyzed. Ablation-induced LGE revealed a higher IIR, suggesting greater contrast uptake and denser fibrosis, than did preexisting LGE (1.25 ± 0.25 vs 1.14 ± 0.15; P < .001). In addition, ablation-induced LGE regions had thinner LA myocardium (2.10 ± 0.67 mm vs 2.37 ± 0.74 mm; P < .001). CONCLUSION: Regions with ablation-induced LGE exhibit increased contrast uptake, likely signifying higher scar density, and thinner myocardium as compared with regions with preexisting LGE. Future studies examining the association of postablation LGE intensity and nonuniformity with ablation success are warranted and may inform strategies to optimize ablation outcome.

The association of pre-existing left atrial fibrosis with clinical variables in patients referred for catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) recurrence after ablation is associated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) magnetic resonance imaging (MRI). We sought to determine pre-ablation, clinical characteristics that associate with the extent of LA fibrosis in patients undergoing catheter ablation for AF. METHODS AND RESULTS: Consecutive patients presenting for catheter ablation of AF were enrolled and underwent LGE-MRI prior to initial AF ablation. The extent of fibrosis as a percentage of total LA myocardium was calculated in all patients prior to ablation. The cohort was divided into quartiles based on the percentage of fibrosis. Of 60 patients enrolled in the cohort, 13 had <5% fibrosis (Group 1), 15 had 5-7% fibrosis (Group 2), 17 had 8-13% fibrosis (Group 3), and 15 had 14-36% fibrosis (Group 4). The extent of LA fibrosis was positively associated with time in continuous AF, and the presence of persistent or longstanding persistent AF. However, no statistically significant difference was observed in the presence of comorbid conditions, age, BMI, LA volume, or family history of AF among the four groups. After adjusting for diabetes and hypertension in a multivariable linear regression model, paroxysmal AF remained independently and negatively associated with the extent of fibrosis (-4.0 ± 1.8, P = 0.034). CONCLUSION: The extent of LA fibrosis in patients undergoing AF ablation is associated with AF type and time in continuous AF. Our results suggest that the presence and duration of AF are primary determinants of increased atrial LGE.

Single nucleotide polymorphisms in proximity to K-channel genes are associated with decreased longitudinal QTc variance.

BACKGROUND: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Despite significant progress in identification of predisposing factors, the pathophysiology of AF remains to be elucidated. Previous studies have reported that single nucleotide polymorphisms (SNPs) in potassium-channel genes associate with AF and the instantaneous corrected QT interval (QTc). The purpose of this study was to examine the association between SNPs in proximity to KCNQ1, KCNH2, KCNE2, and KCNJ2 and longitudinal QTc variations in patients with AF. METHODS AND RESULTS: We conducted a retrospective cohort study of 800 electrocardiograms from 93 patients with AF. All patients were Caucasian, with an average age of 61.2 years, and 72% were male. Of all patients, 37% had persistent AF, and 63% had paroxysmal AF. Following DNA extraction from blood, SNPs at the AF-associated loci KCNQ1, KCNH2, KCNE2, and KCNJ2 were genotyped using the Sequenom MassARRAY. Using a linear regression model and adapting a resampling inference, a decrease in longitudinal QTc variance was found to associate with SNPs near KCNH2 (rs10240738) and KCNJ2 (rs8079702) when adjusted for patient age, gender, AF type, and average QTc. On average, patients with these SNPs had a shorter QTc interval. In addition, we fitted a multilevel mixed effects regression model accounting for subject level heterogeneity and found no longitudinal association between presence of SNPs near K-channel genes and changes in QTc. CONCLUSION: Polymorphisms near specific potassium-channel genes in AF patients are associated with decreased longitudinal QTc variance and a shorter average QTc. These results support the hypothesis that effects on myocardial repolarization may mediate the association of these SNPs and AF.

Magnetic resonance image intensity ratio, a normalized measure to enable interpatient comparability of left atrial fibrosis.

BACKGROUND: The measurement of late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) intensity in arbitrary units limits the objectivity of thresholds for focal scar detection and interpatient comparisons of scar burden. OBJECTIVE: To develop and validate a normalized measure, the image intensity ratio (IIR), for the assessment of left atrial (LA) scar on LGE-MRI. METHODS: Electrocardiogram- and respiratory-gated 1.5 Tesla LGE-MRI was performed in 75 patients (75% men; 62 ± 8 years) before atrial fibrillation ablation. The local IIR was defined as LA myocardial signal intensity for each of the 20 sectors on contiguous axial image planes divided by the mean LA blood pool image intensity. Intracardiac point-by-point sampled electroanatomic map points were coregistered with the corresponding image sectors. RESULTS: The average bipolar voltage for all 8153 electroanatomic map points was 0.9 ± 1.1 mV. In a mixed effects model accounting for within patient clustering, and adjusting for age, LA volume, mass, body mass index, sex, CHA2DS2-VASc score, atrial fibrillation type, history of previous ablations, and contrast delay time, each unit increase in local IIR was associated with 91.3% decrease in bipolar LA voltage (P < .001). Local IIR thresholds of >0.97 and >1.61 corresponded to bipolar voltage <0.5 and <0.1 mV, respectively. CONCLUSIONS: Normalization of LGE-MRI intensity by the mean blood pool intensity results in a metric that is closely associated with intracardiac voltage as a surrogate of atrial fibrosis.

Relationship between left atrial appendage morphology and stroke in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is an important cause of stroke. Given the morbidity and mortality associated with stroke, the risk stratification of patients based on left atrial appendage (LAA) characteristics is of great interest. OBJECTIVE: To explore the association between LAA morphology and LAA characteristics including the extent of trabeculations, orifice diameter, and length with prevalent stroke in a large cohort of patients with drug refractory AF who underwent AF ablation to develop mechanistic insight regarding the risk of stroke. METHODS: An institutional cohort of 1063 patients referred for AF ablation from 2003 to 2012 was reviewed to identify patients that underwent preprocedural cardiac computed tomography (CT). LAA morphology was characterized as chicken wing, cactus, windsock, or cauliflower by using previously reported methodology. Left atrial size and LAA trabeculations, morphology, orifice diameter, and length were compared between patients with prevalent stroke and patients without prevalent stroke. RESULTS: Of 678 patients with CT images, 65 (10%) had prior stroke or transient ischemic attack. In univariate analyses, prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller LAA orifice (2.26 ± 0.52 cm vs 2.78 ± 0.71 cm ; P < .001), shorter LAA length (5.06 ± 1.17 cm vs 5.61 ± 1.17 cm; P < .001), and extensive LAA trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA morphologies were unassociated with stroke risk. In multivariable analysis, smaller LAA orifice diameter and extensive LAA trabeculations remained independently associated with thromboembolic events. CONCLUSIONS: The extent of LAA trabeculations and smaller LAA orifice diameter are associated with prevalent stroke and may mediate the previously described association of cauliflower LAA morphology with stroke.

Cardiac magnetic resonance T1 mapping of left atrial myocardium.

BACKGROUND: Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis. OBJECTIVES: To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures. METHODS: CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements. RESULTS: The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364-428] ms) compared to healthy volunteers (459 [interquartile range 418-532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025). CONCLUSIONS: Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues.

Role of Magnetic Resonance Imaging of Atrial Fibrosis in Atrial Fibrillation Ablation.

Atrial fibrillation (AF) likely involves a complex interplay between triggering activity, usually from pulmonary vein foci, and maintenance of the arrhythmia by an arrhythmogenic substrate. Both components of AF, triggers and substrate have been linked to atrial fibrosis and attendant changes in atrial electrophysiology. Recently, there has been a growing use of imaging modalities, particularly cardiac magnetic resonance (CMR), to quantify the burden of atrial fibrosis and scar in patients either undergoing AF ablation, or who have recently had the procedure. How to use the CMR derived data is still an open area of investigation. The aim of this article is to summarise what is known as atrial fibrosis, as assessed by traditional catheter-based techniques and newer imaging approaches, and to report on novel efforts from our group to advance the use of CMR in AF ablation patients.