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.

CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia (CERTAINTY).

Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.

Extrapolation of Ventricular Activation Times From Sparse Electroanatomical Data Using Graph Convolutional Neural Networks.

Electroanatomic mapping is the gold standard for the assessment of ventricular tachycardia. Acquiring high resolution electroanatomic maps is technically challenging and may require interpolation methods to obtain dense measurements. These methods, however, cannot recover activation times in the entire biventricular domain. This work investigates the use of graph convolutional neural networks to estimate biventricular activation times from sparse measurements. Our method is trained on more than 15,000 synthetic examples of realistic ventricular depolarization patterns generated by a computational electrophysiology model. Using geometries sampled from a statistical shape model of biventricular anatomy, diverse wave dynamics are induced by randomly sampling scar and border zone distributions, locations of initial activation, and tissue conduction velocities. Once trained, the method accurately reconstructs biventricular activation times in left-out synthetic simulations with a mean absolute error of 3.9 ms ± 4.2 ms at a sampling density of one measurement sample per cm2. The total activation time is matched with a mean error of 1.4 ms ± 1.4 ms. A significant decrease in errors is observed in all heart zones with an increased number of samples. Without re-training, the network is further evaluated on two datasets: (1) an in-house dataset comprising four ischemic porcine hearts with dense endocardial activation maps; (2) the CRT-EPIGGY19 challenge data comprising endo- and epicardial measurements of 5 infarcted and 6 non-infarcted swines. In both setups the neural network recovers biventricular activation times with a mean absolute error of less than 10 ms even when providing only a subset of endocardial measurements as input. Furthermore, we present a simple approach to suggest new measurement locations in real-time based on the estimated uncertainty of the graph network predictions. The model-guided selection of measurement locations allows to reduce by 40% the number of measurements required in a random sampling strategy, while achieving the same prediction error. In all the tested scenarios, the proposed approach estimates biventricular activation times with comparable or better performance than a personalized computational model and significant runtime advantages.

Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation.

ABSTRACT: 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 < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV- men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to -1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to -1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.

Characterization of the Electrophysiologic Remodeling of Patients With Ischemic Cardiomyopathy by Clinical Measurements and Computer Simulations Coupled With Machine Learning.

RATIONALE: Patients with ischemic cardiomyopathy (ICMP) are at high risk for malignant arrhythmias, largely due to electrophysiological remodeling of the non-infarcted myocardium. The electrophysiological properties of the non-infarcted myocardium of patients with ICMP remain largely unknown. OBJECTIVES: To assess the pro-arrhythmic behavior of non-infarcted myocardium in ICMP patients and couple computational simulations with machine learning to establish a methodology for the development of disease-specific action potential models based on clinically measured action potential duration restitution (APDR) data. METHODS AND RESULTS: We enrolled 22 patients undergoing left-sided ablation (10 ICMP) and compared APDRs between ICMP and structurally normal left ventricles (SNLVs). APDRs were clinically assessed with a decremental pacing protocol. Using genetic algorithms (GAs), we constructed populations of action potential models that incorporate the cohort-specific APDRs. The variability in the populations of ICMP and SNLV models was captured by clustering models based on their similarity using unsupervised machine learning. The pro-arrhythmic potential of ICMP and SNLV models was assessed in cell- and tissue-level simulations. Clinical measurements established that ICMP patients have a steeper APDR slope compared to SNLV (by 38%, p < 0.01). In cell-level simulations, APD alternans were induced in ICMP models at a longer cycle length compared to SNLV models (385-400 vs 355 ms). In tissue-level simulations, ICMP models were more susceptible for sustained functional re-entry compared to SNLV models. CONCLUSION: Myocardial remodeling in ICMP patients is manifested as a steeper APDR compared to SNLV, which underlies the greater arrhythmogenic propensity in these patients, as demonstrated by cell- and tissue-level simulations using action potential models developed by GAs from clinical measurements. The methodology presented here captures the uncertainty inherent to GAs model development and provides a blueprint for use in future studies aimed at evaluating electrophysiological remodeling resulting from other cardiac diseases.

Quantifying arrhythmic long QT effects of hydroxychloroquine and azithromycin with whole-heart optical mapping and simulations.

BACKGROUND: In March 2020, hydroxychloroquine (HCQ) alone or combined with azithromycin (AZM) was authorized as a treatment for COVID-19 in many countries. The therapy proved ineffective with long QT and deadly cardiac arrhythmia risks, illustrating challenges to determine the new safety profile of repurposed drugs. OBJECTIVE: To investigate proarrhythmic effects and mechanism of HCQ and AZM (combined and alone) with high doses of HCQ as in the COVID-19 clinical trials. METHODS: Proarrhythmic effects of HCQ and AZM are quantified using optical mapping with voltage-sensitive dyes in ex vivo Langendorff-perfused guinea pig (GP) hearts and with numerical simulations of a GP Luo-Rudy and a human O'Hara-Virag-Varro-Rudy models, for Epi, Endo, and M cells, in cell and tissue, incorporating the drug's effect on cell membrane ionic currents. RESULTS: Experimentally, HCQ alone and combined with AZM leads to long QT intervals by prolonging the action potential duration and increased spatial dispersion of action potential (AP) repolarization across the heart, leading to proarrhythmic discordant alternans. AZM alone had a lesser arrhythmic effect with less triangulation of the AP shape. Mathematical cardiac models fail to reproduce most of the arrhythmic effects observed experimentally. CONCLUSIONS: During public health crises, the risks and benefits of new and repurposed drugs could be better assessed with alternative experimental and computational approaches to identify proarrhythmic mechanisms. Optical mapping is an effective framework suitable to investigate the drug's adverse effects on cardiac cell membrane ionic channels at the cellular level and arrhythmia mechanisms at the tissue and whole-organ level.

Association of Longitudinal Changes in NT-proBNP With Changes in Left Atrial Volume and Function: MESA.

BACKGROUND: The mechanism of left atrial (LA) remodeling is poorly understood. The aim of this longitudinal study was to investigate whether changes in NT-proBNP levels relate to alterations of LA structure and function over time in a multiethnic population. METHODS: From the prospective cohort study, the Multi-Ethnic Study of Atherosclerosis, our analysis included 1,838 participants who underwent cardiac magnetic resonance imaging at the baseline and 10-year examinations, had NT-proBNP levels available at both time points, and did not develop heart failure, myocardial infarction, and/or atrial fibrillation. Multivariable linear regression was used to analyze the association between NT-proBNP level (log-transformed) at the 2 time points and change in LA volumes, LA emptying fractions (total, active, and passive), and LA longitudinal strain. Log NT-proBNP was categorized into Low-Low (N = 681), Low-High (N = 238), High-Low (N = 237), and High-High (N = 682) based on the median value at both time points. RESULTS: With the Low-Low group as the reference group, the High-High group experienced a greater increase in LA maximum and minimum indexed volumes: 3.1 ml/m2 (95% confidence interval 1.98, 4.20) and 2.7 ml/m2 (1.89, 3.51), respectively. The High-High group also experienced a greater decrease in LA total, passive, active emptying fraction, and longitudinal strain: -3.3% (-4.46, -2.11), -0.9% (-1.80, -0.02), -4.2% (-5.55, -2.76), and -2.3% (-3.80, -0.72), respectively. The Low-High group had similar associations, but the effect sizes were not as high. CONCLUSIONS: Adverse LA remodeling over 10 years of follow-up strongly correlates with prolonged elevated levels of intracardiac stress, as assessed by NT-proBNP levels.

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.

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.

Baseline and Dynamic Risk Predictors of Appropriate Implantable Cardioverter Defibrillator Therapy.

Background Current approaches fail to separate patients at high versus low risk for ventricular arrhythmias owing to overreliance on a snapshot left ventricular ejection fraction measure. We used statistical machine learning to identify important cardiac imaging and time-varying risk predictors. Methods and Results Three hundred eighty-two cardiomyopathy patients (left ventricular ejection fraction ≤35%) underwent cardiac magnetic resonance before primary prevention implantable cardioverter defibrillator insertion. The primary end point was appropriate implantable cardioverter defibrillator discharge or sudden death. Patient characteristics; serum biomarkers of inflammation, neurohormonal status, and injury; and cardiac magnetic resonance-measured left ventricle and left atrial indices and myocardial scar burden were assessed at baseline. Time-varying covariates comprised interval heart failure hospitalizations and left ventricular ejection fractions. A random forest statistical method for survival, longitudinal, and multivariable outcomes incorporating baseline and time-varying variables was compared with (1) Seattle Heart Failure model scores and (2) random forest survival and Cox regression models incorporating baseline characteristics with and without imaging variables. Age averaged 57±13 years with 28% women, 66% white, 51% ischemic, and follow-up time of 5.9±2.3 years. The primary end point (n=75) occurred at 3.3±2.4 years. Random forest statistical method for survival, longitudinal, and multivariable outcomes with baseline and time-varying predictors had the highest area under the receiver operating curve, median 0.88 (95% CI, 0.75-0.96). Top predictors comprised heart failure hospitalization, left ventricle scar, left ventricle and left atrial volumes, left atrial function, and interleukin-6 level; heart failure accounted for 67% of the variation explained by the prediction, imaging 27%, and interleukin-6 2%. Serial left ventricular ejection fraction was not a significant predictor. Conclusions Hospitalization for heart failure and baseline cardiac metrics substantially improve ventricular arrhythmic risk prediction.

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.

Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19.

BACKGROUND: Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. OBJECTIVE: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. METHODS: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). RESULTS: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. CONCLUSION: The study results further highlight the proarrhythmic effects of HCQ.

Accurate Conduction Velocity Maps and Their Association With Scar Distribution on Magnetic Resonance Imaging in Patients With Postinfarction Ventricular Tachycardias.

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.

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.

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.

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.

Computationally guided personalized targeted ablation of persistent atrial fibrillation.

Atrial fibrillation (AF)-the most common arrhythmia-significantly increases the risk of stroke and heart failure. Although catheter ablation can restore normal heart rhythms, patients with persistent AF who develop atrial fibrosis often undergo multiple failed ablations, and thus increased procedural risks. Here, we present personalized computational modelling for the reliable predetermination of ablation targets, which are then used to guide the ablation procedure in patients with persistent AF and atrial fibrosis. First, we show that a computational model of the atria of patients identifies fibrotic tissue that, if ablated, will not sustain AF. Then, we report the results of integrating the target ablation sites in a clinical mapping system and testing its feasibility in ten patients with persistent AF. The computational prediction of ablation targets avoids lengthy electrical mapping and could improve the accuracy and efficacy of targeted AF ablation in patients while eliminating the need for repeat procedures.

Change in left atrial function predicts incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis.

AIMS: Longitudinal change in left atrial (LA) structure and function could be helpful in predicting risk for incident atrial fibrillation (AF). We used cardiac magnetic resonance (CMR) imaging to explore the relationship between change in LA structure and function and incident AF in a multi-ethnic population free of clinical cardiovascular disease at baseline. METHODS AND RESULTS: In the Multi-Ethnic Study of Atherosclerosis (MESA), 2338 participants, free at baseline of clinically recognized AF and cardiovascular disease, had LA volume and function assessed with CMR imaging, at baseline (2000-02), and at Exam 4 (2005-07) or 5 (2010-12). Free of AF, 124 participants developed AF over 3.8 ± 0.9 years (2015) following the second imaging. In adjusted Cox regression models, an average annualized change in all LA parameters were significantly associated with an increased risk of AF. An annual decrease of 1-SD unit in total LA emptying fractions (LAEF) was most strongly associated with risk of AF after adjusting for clinical risk factors for AF, baseline LA parameters, and left ventricular mass-to-volume ratio (hazard ratio per SD = 1.91, 95% confidence interval = 1.53-2.38, P < 0.001). The addition of change in total LAEF to an AF risk score improved model discrimination and reclassification (net reclassification improvement = 0.107, P = 0.017; integrative discrimination index = 0.049, P < 0.001). CONCLUSION: In this multi-ethnic study population free of clinical cardiovascular disease at baseline, a greater increase in LA volumes and decrease in LA function were associated with incident AF. The addition of change in total LAEF to risk prediction models for AF improved model discrimination and reclassification of AF risk.