Purkinje network and myocardial substrate at the onset of human ventricular fibrillation: implications for catheter ablation.

AIMS: Mapping data of human ventricular fibrillation (VF) are limited. We performed detailed mapping of the activities underlying the onset of VF and targeted ablation in patients with structural cardiac abnormalities. METHODS AND RESULTS: We evaluated 54 patients (50 ± 16 years) with VF in the setting of ischaemic (n = 15), hypertrophic (n = 8) or dilated cardiomyopathy (n = 12), or Brugada syndrome (n = 19). Ventricular fibrillation was mapped using body-surface mapping to identify driver (reentrant and focal) areas and invasive Purkinje mapping. Purkinje drivers were defined as Purkinje activities faster than the local ventricular rate. Structural substrate was delineated by electrogram criteria and by imaging. Catheter ablation was performed in 41 patients with recurrent VF. Sixty-one episodes of spontaneous (n = 10) or induced (n = 51) VF were mapped. Ventricular fibrillation was organized for the initial 5.0 ± 3.4 s, exhibiting large wavefronts with similar cycle lengths (CLs) across both ventricles (197 ± 23 vs. 196 ± 22 ms, P = 0.9). Most drivers (81%) originated from areas associated with the structural substrate. The Purkinje system was implicated as a trigger or driver in 43% of patients with cardiomyopathy. The transition to disorganized VF was associated with the acceleration of initial reentrant activities (CL shortening from 187 ± 17 to 175 ± 20 ms, P < 0.001), then spatial dissemination of drivers. Purkinje and substrate ablation resulted in the reduction of VF recurrences from a pre-procedural median of seven episodes [interquartile range (IQR) 4-16] to 0 episode (IQR 0-2) (P < 0.001) at 56 ± 30 months. CONCLUSIONS: The onset of human VF is sustained by activities originating from Purkinje and structural substrate, before spreading throughout the ventricles to establish disorganized VF. Targeted ablation results in effective reduction of VF burden. KEY QUESTION: The initial phase of human ventricular fibrillation (VF) is critical as it involves the primary activities leading to sustained VF and arrhythmic sudden death. The origin of such activities is unknown. KEY FINDING: Body-surface mapping shows that most drivers (≈80%) during the initial VF phase originate from electrophysiologically defined structural substrates. Repetitive Purkinje activities can be elicited by programmed stimulation and are implicated as drivers in 37% of cardiomyopathy patients. TAKE-HOME MESSAGE: The onset of human VF is mostly associated with activities from the Purkinje network and structural substrate, before spreading throughout the ventricles to establish sustained VF. Targeted ablation reduces or eliminates VF recurrence.

HIV Infection Is Associated With Variability in Ventricular Repolarization: The Multicenter AIDS Cohort Study (MACS).

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 (P<0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). In comparison with HIV- men, HIV+ men had higher QTVI (adjusted difference of +0.077 [95% CI, +0.032 to +0.123]). The magnitude of this association depended on the degree of viremia, such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI, +0.017 to +0.111) higher than in HIV- men, whereas, in HIV+ men with detectable VL, adjusted QTVI was higher by +0.150 (95% CI, 0.072-0.228) than in HIV- referents. Analysis of QTVI subcomponents showed that HIV+ men had: (1) lower heart rate variability irrespective of VL status, and (2) higher QT variability if they had detectable, but not with undetectable, VL, in comparison with HIV- men. Higher levels of C-reactive protein, interleukin-6, intercellular adhesion molecule-1, soluble tumor necrosis factor receptor 2, and soluble cluster of differentiation-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus. CONCLUSIONS: 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.

Short- and long-term associations of atrial fibrillation catheter ablation with left atrial structure and function: A cardiac magnetic resonance study.

BACKGROUND: The effects of atrial fibrillation (AF) catheter ablation on the left atrium (LA) are poorly understood. OBJECTIVES: To examine short- and long-term associations of AF catheter ablation with LA function using cardiac magnetic resonance (CMR). METHODS: Fifty-one AF patients (mean age 56 ± 8 years) underwent CMR at baseline, 1 day (n = 17) and 11 ± 2 months after ablation (n = 38). LA phasic volumes, emptying fractions (LAEF), and longitudinal strain were measured using feature-tracking CMR. LA fibrosis was quantified using late gadolinium enhancement (LGE). RESULTS: There were no acute changes in volume; however, active, total LAEF, and peak LA strain decreased significantly compared to the baseline. During long-term follow-up, there was a decrease in maximum but not minimum LA volume (from 99 ± 5.2 ml to 89 ± 4.7 ml; p = .009) and a decrease in total LAEF (from 43 ± 1.8% to 39 ± 2.0%; p = .001). In patients with AF recurrence, LA volumes were unchanged. However, total LAEF decreased from 38 ± 3% to 33 ± 3%; p = .015. Patients without AF recurrence had no changes in LA functional parameters during follow-up. The amount of LA LGE at long-term follow-up was higher compared to the baseline, however, was significantly less compared to immediately post-procedure (37 ± 1.9% vs. 47 ± 2.8%; p = .015). A higher increase in LA LGE extent compared to the baseline was associated with a greater decrease in total LAEF (r = -.59; p < .001). CONCLUSIONS: LA function is impaired acutely following AF catheter ablation. However, long-term changes of LA function are associated positively with the successful restoration of sinus rhythm and inversely with increased LA LGE.

On the nature of delays allowing anatomical re-entry involving the Purkinje network: a simulation study.

AIMS: Clinical observations suggest that the Purkinje network can be part of anatomical re-entry circuits in monomorphic or polymorphic ventricular arrhythmias. However, significant conduction delay is needed to support anatomical re-entry given the high conduction velocity within the Purkinje network. METHODS AND RESULTS: We investigated, in computer models, whether damage rendering the Purkinje network as either an active lesion with slow conduction or a passive lesion with no excitable ionic channel, could explain clinical observations. Active lesions had compromised sodium current and a severe reduction in gap junction coupling, while passive lesions remained coupled by gap junctions, but modelled the membrane as a fixed resistance. Both types of tissue could provide significant delays of over 100 ms. Electrograms consistent with those obtained clinically were reproduced. However, passive tissue could not support re-entry as electrotonic coupling across the delay effectively increased the proximal refractory period to an extremely long interval. Active tissue, conversely, could robustly maintain re-entry. CONCLUSION: Formation of anatomical re-entry using the Purkinje network is possible through highly reduced gap junctional coupling leading to slowed conduction.

Mechanism of spontaneous initiation of ventricular fibrillation in patients with implantable defibrillators.

INTRODUCTION: To improve the mechanistic understanding of spontaneous initiation of ventricular fibrillation (VF), we characterized the patterns of premature ventricular complex (PVC) preceding spontaneous VF in primary and secondary implantable cardioverter-defibrillator (ICD) recipients. METHODS AND RESULTS: A single-center, cross-sectional analysis of 1209 patients with primary and secondary prevention ICD identified 190 patients who received ICD therapy (firing or antitachycardia pacing) for VF or monomorphic ventricular tachycardia (MMVT). Initiation was quantified by the coupling interval (CI), the cycle length immediately preceding the CI (CL(-1)), the CI corrected by CL(-1) using Fridericia's formula (CIc), and the prematurity index (PI). In both VF (n = 44; 23%) and MMVT (n = 134; 71%), the most common pattern of initiation was late-coupled PVC, followed by the short-long-short pattern. The parameters such as pre-initiation median CL, CL(-1), CI, and PI were not significantly different between VF and MMVT for any patterns. At least some events (45% of VF and 63% of MMVT) had extremely long CIs beyond the QTc cut-off estimated from the CL(-1), suggestive of initiation by a train of multiple PVCs or nonsustained VT instead of a single PVC. CONCLUSION: Some spontaneous VF events in ICD recipients appear to be initiated by a train of multiple PVC or nonsustained VT rather than a single PVC. This finding indicates that patterns of a single PVC are not an important determinant of VF initiation and thus account for conflicting results in previous studies.

Association between interatrial block, left atrial fibrosis, and mechanical dyssynchrony: Electrocardiography-magnetic resonance imaging correlation.

INTRODUCTION: Advanced interatrial block (IAB) on a 12-lead electrocardiogram (ECG) is a predictor of stroke, incident atrial fibrillation (AF), and AF recurrence after catheter ablation. The objective of this study was to determine which features of IAB structural remodeling is associated with left atrium (LA) magnetic resonance imaging structure and function. METHODS/RESULTS: We included 152 consecutive patients (23% nonparoxysmal AF) who underwent preprocedural ECG and cardiac magnetic resonance (CMR) in sinus rhythm before catheter ablation of AF. IAB was defined as P-wave duration ≥120 ms, and was considered partial if P-wave was positive and advanced if P-wave had a biphasic morphology in inferior leads. From cine CMR and late gadolinium enhancement, we derived LA maximum and minimum volume indices, strain, LA fibrosis, and LA dyssynchrony. A total of 77 patients (50.7% paroxysmal) had normal P-wave, 52 (34.2%) partial IAB, and 23 (15.1%) advanced IAB. Patients with advanced IAB had significantly higher LA minimum volume index (25.7 vs 19.9 mL/m2 , P = .010), more LA fibrosis (21.9% vs 13.1%, P = .020), and lower LA maximum strain rate (0.99 vs 1.18, P = .007) than those without. Advanced IAB was independently associated with LA (minimum [P = .032] and fibrosis [P = .009]). P-wave duration was also independently associated with LA fibrosis (ß = .33; P = .049) and LA mechanical dyssynchrony (ß = 2.01; P = .007). CONCLUSION: Advanced IAB is associated with larger LA volumes, lower emptying fraction, and more fibrosis. Longer P-wave duration is also associated with more LA fibrosis and higher LA mechanical dyssynchrony.

Associations between QT interval subcomponents, HIV serostatus, and inflammation.

BACKGROUND: The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. METHODS: Twelve-lead electrocardiograms (ECGs) were acquired in 774 HIV-infected (HIV+) and 652 HIV-uninfected (HIV-) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R-onset to R-peak, R-peak to R-end, JT segment, T-onset to T-peak, and T-peak to T-end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin-6 (IL-6), and each QT subcomponent. RESULTS: After adjustment for demographics and risk factors, HIV+ versus HIV- men differed only in repolarization phase durations with longer T-onset to T-peak by 2.3 ms (95% CI 0-4.5, p < .05) and T-peak to T-end by 1.6 ms (95% CI 0.3-2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL-6 was associated with a 7.3 ms (95% CI 3.2-11.5, p < .01) longer T-onset to T-peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2-12.5 ms longer T-wave subcomponents. CONCLUSIONS: HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T-wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.

Heart rate increase after pulmonary vein isolation predicts freedom from atrial fibrillation at 1 year.

INTRODUCTION: Ablation of atrial vagal ganglia has been associated with improved pulmonary vein isolation (PVI) outcomes. Disruption of vagal reflexes results in heart rate (HR) increase. We investigated the association between HR change after PVI and freedom from atrial fibrillation (AF) at 1 year. METHODS AND RESULTS: Patients who underwent PVI for paroxysmal AF were identified from the Johns Hopkins Hospital AF registry. Electrocardiograms taken pre-PVI and post-PVI were used to determine the change in HR. Patients followed-up at 3, 6, and 12 months. Of 257 patients (66% male, age 59+/-11 years), 134 (52%) remained free from AF at 1 year. The average HR increased from 60.6 ± 11.3 beats per minute (bpm) pre-PVI to 70.7 ± 12.0 bpm post-PVI. Patients with recurrence of AF had lower post-PVI HR than those who remained free from AF (67.8 ± 0.2 vs 73.3 ± 13.0 bpm; P <.001). The probability of AF recurrence at 1-year decreased as the change in HR increased (estimated odds ratio [OR], 0.83; 95% confidence interval [CI, 0.74-0.93]; P = .002). HR increase more than 15 bpm was associated with the lowest odds of AF recurrence (estimated OR, 0.39; 95% [0.17-0.85]; P = .018) compared to HR decrease. CONCLUSIONS: Resting HR was found to increase after PVI. Increase in HR more than 15 bpm has a positive association with remaining free from atrial fibrillation at 1 year.

Increased rates of atrial fibrillation recurrence following pulmonary vein isolation in overweight and obese patients.

INTRODUCTION: Catheter ablation is common for patients with symptomatic, drug-refractory atrial fibrillation (AF). Obesity is a known risk factor for incident AF. The impact of obesity on AF ablation outcomes is incompletely understood. We sought to determine the impact of elevated body mass index (BMI) on pulmonary vein isolation (PVI) procedural outcomes and associated complications. METHODS AND RESULTS: We evaluated patients undergoing PVI from 2001 to 2015, dividing them into four groups: normal weight (BMI ≥ 18.5 to < 25), overweight (BMI ≥ 25 to < 30), obese (BMI > 30 to < 40), and morbidly obese (BMI ≥ 40). Demographic and procedural characteristics, complications, and ablation outcomes were compared among groups. A total of 701 patients (146 time-matched controls, 227 overweight, 244 obese, and 84 morbidly obese) with complete demographic, procedural, and follow-up data were included. Increasing BMI correlated positively with HTN, OSA, CHA2 DS2 -VASC score, and persistent AF (P ≤ 0.001 for all associations). Radiofrequency application time and intraprocedural heparin dose increased with BMI (P ≤ 0.001). Arrhythmia recurrence at 1 year was 39.9% in controls, while higher in all high-BMI groups (overweight, 51.3%; obese, 57%; morbidly obese, 58.1 %; P  =  0.007 for all versus controls). Impact of BMI on AF recurrence was not seen in persistent AF patients. Complication rates across groups were similar. CONCLUSIONS: AF recurrence after catheter ablation is higher in overweight, obese, and morbidly obese patients comparing to normal-weight controls, driven primarily by outcomes differences in paroxysmal AF patients. Complications were not associated with increased BMI.

Current management and clinical outcomes for catheter ablation of atrioventricular nodal re-entrant tachycardia.

Aims: Historical studies of ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) have shown high long-term success rates and low complication rates. The potential impact of several recent practice trends has not been described. This study aims to characterize recent clinical practice trends in AVNRT ablation and their associated success rates and complications. Methods and results: Patients undergoing initial ablation of AVNRT between 1 July 2005 and 30 June 2015 were included in this study. Patient demographics and procedural data were abstracted from procedure reports. Follow-up data, including AVNRT recurrence and complications, was evaluated through electronic medical record review. In total, 877 patients underwent catheter ablation for AVNRT. By the last recorded year, three-dimension (3D) electroanatomical mapping (EAM) was used in 36.2%, 43.2% included anaesthesia, and 23.1% utilized irrigated catheters. Long-term procedural success was 95.5%. The use of anaesthesia, 3D EAM, and irrigated ablation catheters were not associated with differences in success. The presence of an atrial 'echo' or 'AH' jump at the end of an acutely successful procedure was not associated with long-term recurrence (P = 0.18, P = 0.15, respectively). Complications, including AV block requiring a pacemaker (0.4%), were uncommon. Conclusion: In a large, contemporary cohort, catheter ablation for AVNRT remains highly successful with low complications rates. The increased use of anaesthesia as well as modern mapping and ablation tools were not associated with changes in clinical outcomes. Further prospective evaluation of such contemporary practices is warranted given the lack of evidence to support their escalating use.

Impact of number of co-existing rotors and inter-electrode distance on accuracy of rotor localization.

BACKGROUND: Conflicting evidence exists on the efficacy of focal impulse and rotor modulation on atrial fibrillation ablation. A potential explanation is inaccurate rotor localization from multiple rotors coexistence and a relatively large (9-11mm) inter-electrode distance (IED) of the multi-electrode basket catheter. METHODS AND RESULTS: We studied a numerical model of cardiac action potential to reproduce one through seven rotors in a two-dimensional lattice. We estimated rotor location using phase singularity, Shannon entropy and dominant frequency. We then spatially downsampled the time series to create IEDs of 2-30mm. The error of rotor localization was measured with reference to the dynamics of phase singularity at the original spatial resolution (IED=1mm). IED has a significant impact on the error using all the methods. When only one rotor is present, the error increases exponentially as a function of IED. At the clinical IED of 10mm, the error is 3.8mm (phase singularity), 3.7mm (dominant frequency), and 11.8mm (Shannon entropy). When there are more than one rotors, the error of rotor localization increases 10-fold. The error based on the phase singularity method at the clinical IED of 10mm ranges from 30.0mm (two rotors) to 96.1mm (five rotors). CONCLUSIONS: The magnitude of error of rotor localization using a clinically available basket catheter, in the presence of multiple rotors might be high enough to impact the accuracy of targeting during AF ablation. Improvement of catheter design and development of high-density mapping catheters may improve clinical outcomes of FIRM-guided AF ablation.

Inter-scale information flow as a surrogate for downward causation that maintains spiral waves.

A rotor, the rotation center of spiral waves, has been proposed as a causal mechanism to maintain atrial fibrillation (AF) in human. However, our current understanding of the causality between rotors and spiral waves remains incomplete. One approach to improving our understanding is to determine the relationship between rotors and downward causation from the macro-scale collective behavior of spiral waves to the micro-scale behavior of individual components in a cardiac system. This downward causation is quantifiable as inter-scale information flow that can be used as a surrogate for the mechanism that maintains spiral waves. We used a numerical model of a cardiac system and generated a renormalization group with system descriptions at multiple scales. We found that transfer entropy quantified the upward and downward inter-scale information flow between micro- and macro-scale descriptions of the cardiac system with spiral waves. In addition, because the spatial profile of transfer entropy and intrinsic transfer entropy was identical, there were no synergistic effects in the system. Furthermore, inter-scale information flow significantly decreased as the description of the system became more macro-scale. Finally, downward information flow was significantly correlated with the number of rotors, but the higher numbers of rotors were not necessarily associated with higher downward information flow. This finding contradicts the concept that the rotors are the causal mechanism that maintains spiral waves, and may account for the conflicting evidence from clinical studies targeting rotors to eliminate AF.

Is human atrial fibrillation stochastic or deterministic?-Insights from missing ordinal patterns and causal entropy-complexity plane analysis.

The mechanism of atrial fibrillation (AF) maintenance in humans is yet to be determined. It remains controversial whether cardiac fibrillatory dynamics are the result of a deterministic or a stochastic process. Traditional methods to differentiate deterministic from stochastic processes have several limitations and are not reliably applied to short and noisy data obtained during clinical studies. The appearance of missing ordinal patterns (MOPs) using the Bandt-Pompe (BP) symbolization is indicative of deterministic dynamics and is robust to brief time series and experimental noise. Our aim was to evaluate whether human AF dynamics is the result of a stochastic or a deterministic process. We used 38 intracardiac atrial electrograms during AF from the coronary sinus of 10 patients undergoing catheter ablation of AF. We extracted the intervals between consecutive atrial depolarizations (AA interval) and converted the AA interval time series to their BP symbolic representation (embedding dimension 5, time delay 1). We generated 40 iterative amplitude-adjusted, Fourier-transform (IAAFT) surrogate data for each of the AA time series. IAAFT surrogates have the same frequency spectrum, autocorrelation, and probability distribution with the original time series. Using the BP symbolization, we compared the number of MOPs and the rate of MOP decay in the first 1000 timepoints of the original time series with that of the surrogate data. We calculated permutation entropy and permutation statistical complexity and represented each time series on the causal entropy-complexity plane. We demonstrated that (a) the number of MOPs in human AF is significantly higher compared to the surrogate data (2.7 ± 1.18 vs. 0.39 ± 0.28, p < 0.001); (b) the median rate of MOP decay in human AF was significantly lower compared with the surrogate data (6.58 × 10-3 vs. 7.79 × 10-3, p < 0.001); and (c) 81.6% of the individual recordings had a rate of decay lower than the 95% confidence intervals of their corresponding surrogates. On the causal entropy-complexity plane, human AF lay on the deterministic part of the plane that was located above the trajectory of fractional Brownian motion with different Hurst exponents on the plane. This analysis demonstrates that human AF dynamics does not arise from a rescaled linear stochastic process or a fractional noise, but either a deterministic or a nonlinear stochastic process. Our results justify the development and application of mathematical analysis and modeling tools to enable predictive control of human AF.

Electrocardiographic Impact of Myocardial Diffuse Fibrosis and Scar: MESA (Multi-Ethnic Study of Atherosclerosis).

Purpose To examine the associations of myocardial diffuse fibrosis and scar with surface electrocardiographic (ECG) parameters in individuals free of prior coronary heart disease in four different ethnicities. Materials and Methods This prospective cross-sectional study was approved by the institutional review boards, and all participants gave informed consent. A total of 1669 participants in the Multi-Ethnic Study of Atherosclerosis, or MESA, who were free of prior myocardial infarction underwent both ECG and cardiac magnetic resonance imaging. In individuals without a late gadolinium enhancement-defined myocardial scar (n = 1131), T1 mapping was used to assess left ventricular (LV) interstitial diffuse fibrosis. The associations of LV diffuse fibrosis or myocardial scar with ECG parameters (QRS voltage, QRS duration, and corrected QT interval [QTc]) were evaluated by using multivariable regression analyses adjusted for demographic data, risk factors for scar, LV end-diastolic volume, and LV mass. Results The mean age of the 1669 participants was 67.4 years ± 8.7 (standard deviation); 49.8% were women. Lower postcontrast T1 time at 12 minutes was significantly associated with lower QRS Sokolow-Lyon voltage (ß = 15.1 µV/10 msec, P = .004), lower QRS Cornell voltage (ß = 9.2 µV/10 msec, P = .031), and shorter QRS duration (ß = 0.16 msec/10 msec, P = .049). Greater extracellular volume (ECV) fraction was also significantly associated with lower QRS Sokolow-Lyon voltage (ß = -35.2 µV/1% ECV increase, P < .001) and Cornell voltage (ß = -23.7 µV/1% ECV increase, P < .001), independent of LV structural indexes. In contrast, the presence of LV scar (n = 106) was associated with longer QTc (ß = 4.3 msec, P = .031). Conclusion In older adults without prior coronary heart disease, underlying greater LV diffuse fibrosis is associated with lower QRS voltage and shorter QRS duration at surface ECG, whereas clinically unrecognized myocardial scar is associated with a longer QT interval. © RSNA, 2016 Online supplemental material is available for this article.

Impaired left atrial function predicts inappropriate shocks in primary prevention implantable cardioverter-defibrillator candidates.

INTRODUCTION: Inappropriate implantable cardioverter-defibrillator (ICD) shocks, commonly caused by atrial fibrillation (AF), are associated with an increased mortality. Because impaired left atrial (LA) function predicts development of AF, we hypothesized that impaired LA function predicts inappropriate shocks beyond a history of AF. METHODS AND RESULTS: We prospectively analyzed the association between LA function and incident inappropriate shocks in primary prevention ICD candidates. In the Prospective Observational Study of ICD (PROSE-ICD), we assessed LA function using tissue-tracking cardiac magnetic resonance (CMR) prior to ICD implantation. A total of 162 patients (113 males, age 56 ± 15 years) were included. During the mean follow-up of 4.0 ± 2.9 years, 26 patients (16%) experienced inappropriate shocks due to AF (n = 19; 73%), supraventricular tachycardia (n = 5; 19%), and abnormal sensing (n = 2; 8%). In univariable analyses, inappropriate shocks were associated with AF history prior to ICD implantation, age below 70 years, QRS duration less than 120 milliseconds, larger LA minimum volume, lower LA stroke volume, lower LA emptying fraction, impaired LA maximum and preatrial contraction strains (Smax and SpreA ), and impaired LA strain rate during left ventricular systole and atrial contraction (SRs and SRa ). In multivariable analysis, impaired Smax (hazard ratio [HR]: 0.96, P = 0.044), SpreA (HR: 0.94, P = 0.030), and SRa (HR: 0.25, P < 0.001) were independently associated with inappropriate shocks. The receiver-operating characteristics curve showed that SRa improved the predictive value beyond the patient demographics including AF history (P = 0.033). CONCLUSION: Impaired LA function assessed by tissue-tracking CMR is an independent predictor of inappropriate shocks in primary prevention ICD candidates beyond AF history.

Factors impacting complication rates for catheter ablation of atrial fibrillation from 2003 to 2015.

Aims: Complications from catheter ablation for atrial fibrillation (AF) are well described. Changing aspects of AF ablation including patient populations referred, institutional experience, and emerging catheter and pharmacological options may impact complication rates. We assessed procedural complication trends in AF ablation patients from 2003­2015 to identify what factors affect adverse event rates. Methods and Results: We evaluated consecutively enrolled patients undergoing initial AF ablation from 2003 through 2015. Statistical analyses were performed to identify predictors of increased risk for major complications, which were defined as death, stroke, atrio-oesophageal fistula, phrenic nerve injury, cardiovascular events requiring blood transfusions or procedural interventions, or non-cardiovascular events requiring intervention. A total of 1475 patients (mean age 59.5 ± 10.5, 82% male) were evaluated. Major complications occurred in 3.9% (n = 58) of cases, including vascular access-site haematoma (1.3%), cardiac tamponade (1.1%), and cerebrovascular accident (CVA) (0.9%). Univariate analysis revealed increased risk of complications associated with hypertension (P = 0.048), CHA2DS2VASc score ≥1 (P = 0.015), and early institutional experience (P = 0.003). Populations with higher CHA2DS2VASc scores underwent AF ablation more frequently over time (P < 0.001). Novel catheters and anticoagulants did not appreciably affect complication rates. Multivariate analysis adjusting for hypertension, CHA2DS2VASc score, and institutional experience showed that higher CHA2DS2VASc score and early institutional experience were independent predictors of adverse events. Conclusion: 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.

Clinical predictors of cardiac magnetic resonance late gadolinium enhancement in patients with atrial fibrillation.

AIMS: This study aims to examine the association of clinical co-morbidities with the presence of left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). Previous studies have established the severity of LA LGE to be associated with atrial fibrillation (AF) recurrence following AF ablation. We sought to determine whether baseline clinical characteristics were associated with LGE extent among patients presenting for an initial AF ablation. METHODS AND RESULTS: The cohort consisted of 179 consecutive patients with no prior cardiac ablation procedures who underwent pre-procedure LGE-CMR. The extent of LA LGE for each patient was calculated using the image intensity ratio, normalized to the mean blood pool intensity, corresponding to a bipolar voltage ≤0.3 mV. The association of LGE extent with baseline clinical characteristics was examined using non-parametric and multivariable models. The mean age of the cohort was 60.9 ± 9.6 years and 128 (72%) were male. In total, 56 (31%) patients had persistent AF. The mean LA volume was 118.4 ± 41.6 mL, and the mean LA LGE extent was 14.1 ± 10.4%. There was no association with any clinical variables with LGE extent by quartiles in the multivariable model. Extent of LGE as a continuous variable was positively, but weakly associated with LA volume in a multivariable model adjusting for age, body mass index, AF persistence, and left ventricular ejection fraction (1.5% scar/mL, P = 0.038). CONCLUSION: In a cohort of patients presenting for initial AF ablation, the presence of pre-ablation LA LGE extent was weakly, but positively associated with increasing LA volume.

Hidden structures of information transport underlying spiral wave dynamics.

A spiral wave is a macroscopic dynamics of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because the spiral wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying the spiral wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of spiral waves. We show that, by defining the information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying the spiral wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings provide validity with our approach to quantitatively characterize the spiral wave dynamics by focusing on information transport. Our approach is computationally efficient and is applicable to many excitable media of interest in distinct physical, chemical, and biological systems. Our approach could ultimately contribute to an improved therapy of clinical conditions such as seizures and cardiac arrhythmia by identifying potential targets of interventional therapies.

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.

Quantitative assessment of atrial regional function using motion estimation computed tomography.

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.