Search

Introduction: Computational modeling-guided, personalized electrophysiology (EP) intervention for atrial fibrillation (AF) is an emerging paradigm of precision medicine. In the published models, advanced imaging and invasive mapping achieve personalization of cardiac anatomy. However, EP cellular personalization is less developed, and parameters are often assumed to be uniform across individual patients Hypothesis: Anatomical personalization alone is not sufficient to recapitulate the individual clinical features of AF in personalized models. Methods: For each of 57 patients (66±10 yr, 30 persistent) referred for catheter ablation of AF, we constructed a personalized 3-D model using pre-ablation CT, invasive mapping, and Courtemanche-Ramirez-Nattel atrial cell model. In the pre-ablation model, we performed virtual ramp pacing with cycle lengths at 200-120ms within the coronary sinus to induce AF. AF was defined as being inducible when it persists for >15s. Simulation was repeated for 5 different published sets of EP parameters of ionic currents. In total, >10k simulations were performed on an NVIDIA V100 GPU cluster, using the Lattice Boltzmann method with spatial resolution of 0.5mm and temporal resolution of 0.05ms, achieving a runtime of 24s per 1s of simulation ( Fig. A ). Results: While 100% AF inducibility was expected in the personalized pre-ablation models, AF inducibility varied between 27% and 96% depending on the set of ionic parameters used ( Fig. B ). The large variability of AF inducibility indicates that those models are highly sensitive to EP parameters, therefore anatomical personalization alone cannot adequately constrain the individual features of AF. Conclusions: The patient-specificity of the current paradigm of modeling-guided, personalized EP intervention is limited. There is an unmet clinical need for incorporation of personalized EP as well as anatomical parameters to achieve true precision medicine.

Background:People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV–) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance.Methods:We studied 1123 men (589 HIV+ and 534 HIV–) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1–quartile 3]: 78.3 [66.3–83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers.Results:Mean (SD) age was 60.1 (11.9) years among HIV– and 54.2 (11.2) years among HIV+ participants (PConclusions:HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV– men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction.

Background: Characterizing myocardial conduction velocity (CV) in patients with ischemic cardiomyopathy (ICM) and ventricular tachycardia (VT) is important for understanding the patient-specific proarrhythmic substrate of VTs and therapeutic planning. The objective of this study is to accurately assess the relation between CV and myocardial fibrosis density on late gadolinium–enhanced cardiac magnetic resonance imaging (LGE-CMR) in patients with ICM. Methods: We enrolled 6 patients with ICM undergoing VT ablation and 5 with structurally normal left ventricles (controls) undergoing premature ventricular contraction or VT ablation. All patients underwent LGE-CMR and electroanatomic mapping (EAM) in sinus rhythm (2960 electroanatomic mapping points analyzed). We estimated CV from electroanatomic mapping local activation time using the triangulation method that provides an accurate estimate of CV as it accounts for the direction of wavefront propagation. We evaluated the association between LGE-CMR intensity and CV with multilevel linear mixed models. Results: Median CV in patients with ICM and controls was 0.41 m/s and 0.65 m/s, respectively. In patients with ICM, CV in areas with no visible fibrosis was 0.81 m/s (95% CI, 0.59–1.12 m/s). For each 25% increase in normalized LGE intensity, CV decreased by 1.34-fold (95% CI, 1.25–1.43). Dense scar areas have, on average, 1.97- to 2.66-fold slower CV compared with areas without dense scar. Ablation lesions that terminated VTs were localized in areas of slow conduction on CV maps. Conclusions: CV is inversely associated with LGE-CMR fibrosis density in patients with ICM. Noninvasive derivation of CV maps from LGE-CMR is feasible. Integration of noninvasive CV maps with electroanatomic mapping during substrate mapping has the potential to improve procedural planning and outcomes. Visual Overview: A visual overview is available for this article.

Background: Previous studies showed that the quantity of the left atrial (LA) periatrial fat tissue predicts recurrence after catheter ablation of atrial fibrillation (AF). We hypothesized that the quality of the LA periatrial fat tissue, measured by the mean computed tomography attenuation, predicts recurrence after AF ablation independent of the quantity of the LA periatrial fat tissue. Methods: We included 143 consecutive patients with drug-refractory AF referred for the first catheter ablation of AF (62.2±10 years, 40% nonparoxysmal AF). All participants had a preablation cardiac computed tomography. We measured the quantity of the LA periatrial fat tissue by the area (millimeter square) and the quality by the mean computed tomography attenuation (Hounsfield units) in a standard 4-chamber view. Results: Patients with AF recurrence after ablation (n=57) had a significantly larger fat area (167.6 [interquartile range, 124.1–255] versus 145.4 [95.6–229.3] mm 2 ; P =0.018) and a higher fat attenuation (−92.0±9.8 versus −96.5±9.4 Hounsfield units; P =0.006) than those without recurrence (controls). LA fat attenuation was correlated with LA fat volume and LA bipolar voltage by invasive mapping and was associated with AF recurrence after adjusting for clinical risk factors, including body mass index, AF type, LA dimension, and fat area (hazard ratio, 2.65; P =0.001). Conclusions: The quality of the LA periatrial fat tissue is an independent predictor of recurrence after the first AF ablation. Assessment of LA periatrial fat attenuation can improve AF ablation outcomes by refining patient selection.

Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study. A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV–) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors. HIV+ men were younger than HIV– men (median 55.5 vs 61.7 years, P

Radiofrequency ablation is an effective treatment strategy for ischemic and nonischemic cardiomyopathy-related ventricular tachycardia (VT). The role of substrate-guided ablation, performed using electrogram characteristics (low amplitude, fractionated or isolated potentials) as scar surrogates, is expanding because of frequent hemodynamic instability during entrainment mapping of scar-related VT. Late gadolinium-enhancement on cardiac magnetic resonance imaging (LGE-MRI) can accurately characterize the transmural extent, location, and configuration of ventricular scar.1 Integration of LGE-MRI into electroanatomical mapping during VT ablation was shown, in preliminary studies, to be feasible and to provide accurate localization of VT substrate and reentry circuits.2–4 However, studies to date examining the impact of MRI scar integration on procedural outcomes have lacked control groups, precluding any comparisons with standard practice. We performed a study to (1) demonstrate the feasibility in clinical practice of integrating MRI-derived scar for guidance of VT ablation; (2) report on the periprocedural performance of LGE-MRI in identifying the arrhythmogenic substrate; and (3) examine the impact of MRI-guided ablation on procedural length and acute and long-term outcomes. In this prospective multicenter study, we enrolled 24 consecutive patients with ischemic (n=9) and nonischemic cardiomyopathy (n=15), referred for catheter ablation of scar-related monomorphic VT. Patients were assigned, at the discretion of the treating physician (not randomized), to undergo either MRI-derived scar–guided ablation or traditional ablation. Clinical characteristics of patients in both groups were statistically comparable with a higher tendency to use scar integration for patients with prior …

OBJECTIVES We validated a novel image-based motion estimation computed tomographic (CT) technique (iME) to quantify atrial regional function in swine in vivo. MATERIALS AND METHODS Domestic swine (n = 8) underwent CT scan with intravenous contrast before and after median sternotomy where 15 to 30 glass beads were sutured to the atria to calculate the motion estimation error. Four-dimensional motion vector field was estimated using iME. Area change ratio (%AC) was calculated over the atrial endocardium to assess the surface deformation. RESULTS The error between the measured and the calculated coordinates based on motion vector field was 0.76 ± 0.43 mm. The %AC was regionally heterogeneous. The %AC time course was significantly different between the right and the left atriums (P < 0.001) as well as between the right atrial appendage and the right atrial chamber (P = 0.004). CONCLUSIONS Quantitative assessment of atrial regional function using iME is highly accurate. Image-based motion estimation computed tomographic (CT) technique can quantify subtle regional dysfunction that is not apparent in global functional indices such as ejection fraction.

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 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.

Background— Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. Methods and Results— An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (≈5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. Conclusions— To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

Introduction: Left ventricular hypertrophy (LVH) is associated with incident heart failure (HF), and ECG strain is a marker of LVH. This study sought to evaluate the relationship of baseline ECG strain to the incidence of HF, longitudinal change of left ventricular (LV) geometry and function by cardiac magnetic resonance imaging (CMR). Methods: A total of 4,732 participants (mean age 61 years, 54% women) free of cardiovascular disease (CVD) underwent ECG and CMR. We used univariable and multivariable Cox proportional hazards to evaluate the association of ECG strain with incident HF (n=137). We also examined the association of baseline ECG strain with changes of LV geometry and function in 2,846 participants imaged at baseline and 10 years later using multiple linear regression models. Finally, we evaluated the association between the presence of ECG strain and LV scar defined by late Gadolinium enhancement at year 10 (n=1,650). Results: The presence of ECG strain was significantly associated with incident HF (hazard ratio: 2.53; 95% CI: 1.40 to 4.57; p=0.021) during follow-up (median 11.2 years). Longitudinal analysis revealed that the presence of ECG strain at baseline was significantly associated with an increase in the LV mass index (β=5.54g/m2, p Conclusions: In a cohort of middle-aged participants without prior CVD, ECG strain was an independent predictor of new-onset HF. In addition, ECG strain was related to development of LV concentric hypertrophy and decline in EF as well as LV scar.

Recent evidence suggests that pulmonary vein isolation (PVI) may perturb the electrophysiological substrate for maintenance of atrial fibrillation (AF). Our previous work indicates that information theory metrics can quantify electrical communications during arrhythmia. We hypothesized that PVI ‘rewires’ the electrical communication network during AF such that the topology exhibits higher levels of small-world network properties, with higher clustering coefficient and lower path length, than would be expected by chance. Thirteen consecutive patients (n=6 with prior PVI and n=7 without) underwent AF ablation using a 64-electrode basket catheter in the left atrium. Multielectrode recording was performed during AF for 60 seconds, followed by PVI. Mutual information was calculated from the time series between each pair of electrodes using the Kraskov-Stögbauer-Grassberger estimator. The all-to-all mutual information matrix (64x64; Figure, upper panels) was thresholded by the median and standard deviations of mutual information to build a binary adjacency matrix for electrical communication networks. The properties of small-world network ( swn ; ‘small-world-ness’) were quantified by the ratio of the observed average clustering coefficient to that of a random network over the ratio of the observed average path length to that of a random network. swn was expressed in normal Z standard deviation units. As the binarizing threshold increased, the Z-score of swn decreased (Figure, lower panel). However, the Z-score at each threshold value was consistently higher with prior PVI than those without (pswn of electrical communication network may be a promising metric to quantify substrate modification.

Backgrounds: Prolonged QRS duration (QRSd) on electrocardiogram (ECG) is commonly found in otherwise healthy individuals. However, geometrical factors of the ventricles that determine QRSd are poorly defined. T1 time by cardiovascular magnetic resonance (CMR) is good parameter to estimate extracellular expansion (ECE). Our objective was to evaluate the relationship between QRSd and CMR measures of tissue composition in a large community-based multiethnic population. Methods: A total of 1,615 participants (52% women; age range 44 to 84 years) of the MESA cohort were evaluated with T1 mapping by using 1.5-T CMR scanners. We excluded the participants with focal scar on delayed enhancement CMR and bundle branch block. Midventricular short-axis T1 maps were acquired before and at 12- and 25-min after administration of gadolinium contrast using Modified Look-Locker Inversion Recovery sequence. Results: Longer QRSd was associated with greater LV end diastolic volume (LVEDV) index (p Conclusions: In a large multiethnic population, longer QRSd was associated with lower ECE and LV dysfunction in women. However, these relationships were sex dependent and were absent in men.

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 P P P 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.

Introduction: Atrial fibrillation (AF) is associated with left atrial (LA) electrical, structural, and contractile remodeling. Cardiac magnetic resonance (CMR), late gadolinium enhancement (LGE) and feature tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. Hypothesis: Increased LA fibrosis measured with LGE is associated with worsening of the phasic LA function measured with feature tracking CMR. Methods: The cohort included 90 patients (age 61 ± 10 years, 76% male) with symptomatic drug-resistant AF referred for ablation. Peak global longitudinal LA strain (PLAS), LA systolic strain rate (SR-s), and early (SR-ed) and late diastolic (SR-ld) strain rates were measured using cine-CMR images acquired during sinus rhythm. The degree of LGE was quantified using normalized image intensity. Results: Compared to patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (LAVImax, 56 ± 17ml/m2 versus 49 ± 13ml/m2 p=0.036), and increased LGE (27.1± 11.7% versus 36.8 ± 14.8% p Conclusions: Increased LA fibrosis is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking CMR is feasible and may add important information regarding the physiological importance of LA fibrosis.

Background: Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF. Methods: Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model. Results: A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score. Conclusions: LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.