Journal: Circ Arrhythm Electrophysiol

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Abstract

Accurate Conduction Velocity Maps and their Association with Scar Distribution on Magnetic Resonance Imaging in Patients with Post-Infarction Ventricular Tachycardias.

Aronis KN, Ali RL, Prakosa A, Ashikaga H, ... Chrispin J, Trayanova NA

- Characterizing myocardial conduction velocity (CV) in patients with ischemic cardiomyopathy (ICM) and ventricular tachycardia (VT) is important for understanding the patient-specific pro-arrhythmic 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 (LGE-CMR) imaging in patients with ICM.- We enrolled 6 patients with ICM undergoing VT ablation and 5 with structurally normal left ventricles (controls) undergoing PVC or VT ablation. All patients underwent LGE-CMR and electro-anatomical mapping (EAM) in sinus rhythm (2,960 EAM points analyzed). We estimated CV from EAM 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 for the association between LGE-CMR intensity and CV with multi-level linear mixed models.- Median CV in ICM patients and controls was 0.41 m/s and 0.65 m/s respectively. In ICM patients, 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 1.97-2.66-fold slower CV compared to areas without dense scar. Ablation lesions that terminated VTs were localized in areas of slow conduction on CV maps.- CV is inversely associated with LGE-CMR fibrosis density in patients with ICM. Non-invasive derivation of CV maps from LGE-CMR is feasible. Integration of non-invasive CV maps with EAM during substrate mapping has the potential to improve procedural planning and outcomes.



Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print
Aronis KN, Ali RL, Prakosa A, Ashikaga H, ... Chrispin J, Trayanova NA
Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print | PMID: 32191131
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Abstract

Left Bundle Branch Block: Current and Future Perspectives.

Tan NY, Witt CM, Oh JK, Cha YM

Left bundle branch block (LBBB) may be due to conduction system degeneration or a reflection of myocardial pathology. LBBB may also develop following aortic valve disease or cardiac procedures. Patients with heart failure with reduced ejection fraction (HFrEF) and LBBB may respond positively to cardiac resynchronization therapy (CRT). Lead placement via the coronary sinus is the mainstay approach of CRT. However, other options including physiologic pacing are being explored. In this review, we summarize the salient pathophysiologic and clinical aspects of LBBB, as well as current and future strategies for management.



Circ Arrhythm Electrophysiol: 17 Mar 2020; epub ahead of print
Tan NY, Witt CM, Oh JK, Cha YM
Circ Arrhythm Electrophysiol: 17 Mar 2020; epub ahead of print | PMID: 32186936
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Abstract

Substrate Spatial Complexity Analysis for the Prediction of Ventricular Arrhythmias in Patients with Ischemic Cardiomyopathy.

Okada DR, Miller J, Chrispin J, Prakosa A, ... Maggioni M, Wu KC

- Transition zones between healthy myocardium and scar form a spatially complex substrate that may give rise to reentrant ventricular arrhythmias (VA). We sought to assess the utility of a novel machine learning (ML) approach for quantifying 3D spatial complexity of grayscale patterns on late gadolinium enhanced cardiac magnetic resonance images (LGE-CMR) to predict VA in patients with ischemic cardiomyopathy (ICM).- 122 consecutive ICM patients with left ventricular ejection fraction ≤35% without prior history of VA underwent LGE-CMR. From raw grayscale data, we generated graphs encoding the 3D geometry of the left ventricle (LV). A novel technique, adapted to these graphs, assessed global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity (SSC) profile for each patient. An ML statistical algorithm was employed to discern which SSC profiles correlated with VA events (appropriate ICD firings and arrhythmic sudden cardiac death) at 5 years of follow-up. From the statistical ML results, a complexity score (CS) ranging from 0-1 was calculated for each patient and tested using multivariable Cox regression models.- At 5 years of follow-up, 40 patients had VA events. The ML algorithm classified with 81% overall accuracy and correctly classified 86% of those without VA. Overall negative predictive value was 91%. Average CS was significantly higher in patients with VA events versus those without (0.5 ± 0.5 vs 0.1 ± 0.2; p<0.0001) and was independently associated with VA events in a multivariable model (hazard ratio = 1.5 [1.2- 2.0]; p=0.002).- SSC analysis of LGE-CMR images may be helpful in refining VA risk in patients with ICM, particularly to identify low risk patients who may not benefit from prophylactic ICD therapy.



Circ Arrhythm Electrophysiol: 17 Mar 2020; epub ahead of print
Okada DR, Miller J, Chrispin J, Prakosa A, ... Maggioni M, Wu KC
Circ Arrhythm Electrophysiol: 17 Mar 2020; epub ahead of print | PMID: 32188287
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Abstract

Accumulation of Pericardial Fat Is Associated with Alterations in Heart Rate Variability Patterns in Hypercholesterolemic Pigs.

Uceda DE, Zhu XY, Woollard JR, Ferguson CM, ... Lerman A, Lerman LO

- Heart rate variability (HRV) or pulse rate variability are indices of autonomic cardiac modulation. Increased pericardial fat is associated with worse cardiovascular outcomes. We hypothesized that progressive increases in pericardial fat volume and inflammation prospectively dampen HRV in hypercholesterolemic pigs.- Wild-type (WT) or PCSK9 gain-of-function Ossabaw mini-pigs were studied in-vivo before and after 3- and 6-months of a normal-diet (WT-ND n=4, PCSK9-ND n=6) or high-fat diet (WT-HFD n=3, PCSK9-HFD n=6). The arterial pulse waveform was obtained from an arterial telemetry transmitter to analyze HRV indices, including standard deviation (SDNN), root-mean-square of successive differences (RMSSD), proportion >50 milliseconds (pNN50) of normal-to-normal RR-intervals, and the calculated ratio of low-to-high frequency distributions (LF/HF). Pericardial fat volumes were evaluated using multidetector computed-tomography, and its inflammation by gene expression of tumor necrosis-factor (TNF)-α. Plasma lipid panel and norepinephrine level were also measured.- At diet completion, hypercholesterolemic PCSK9-HFD had significantly (p<0.05 vs. baseline) depressed HRV (SDNN, RMSSD, pNN50, HF, LF), and both HFD groups had higher sympathovagal balance (SDNN/RMSSD, LF/HF) compared to ND. Pericardial fat volumes and LDL-C concentrations correlated inversely with HRV and directly with sympathovagal balance, while sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF-α expression was upregulated in PCSK9-HFD, co-localized with nerve fibers, and correlated inversely with RMSSD and pNN50.- Progressive pericardial fat expansion and inflammation are associated with a fall in HRV in Ossabaw mini-pigs, implying aggravated autonomic imbalance. Hence, pericardial fat accumulation is associated with alterations in HRV and the autonomic nervous system.



Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print
Uceda DE, Zhu XY, Woollard JR, Ferguson CM, ... Lerman A, Lerman LO
Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print | PMID: 32189516
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Abstract

Diagnosis-to-Ablation Time and Recurrence of Atrial Fibrillation Following Catheter Ablation: A Systematic Review and Meta-analysis of Observational Studies.

Chew DS, Black-Maier E, Loring Z, Noseworthy PA, ... Mark DB, Piccini JP

- The optimal timing of catheter ablation for atrial fibrillation (AF) in reference to the time of diagnosis is unknown. We sought to assess the impact of the duration between first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), on AF recurrence following catheter ablation.- We conducted a systematic electronic search for observational studies reporting the outcomes associated with catheter ablation for atrial fibrillation stratified by diagnosis-to-ablation time. The primary meta-analysis using a random effects model assessed AF recurrence stratified by DAT ≤ 1 year versus = 1 year. A secondary analysis assessed outcomes stratified by DAT ≤ 3 years versus = 3 years.- Of the 632 screened studies, 6 studies met inclusion criteria for a total of 4,950 participants undergoing AF ablation for symptomatic AF. A shorter DAT ≤ 1 year was associated with a lower relative risk (RR) of AF recurrence compared to DAT = 1 year (RR 0.73; 95% confidence interval (CI) 0.65 to 0.82, p<0.001). Heterogeneity was moderate (I=51%). When excluding the one study consisting of only persistent AF patients, the heterogeneity improved substantially (I=0%, Cochran\'s Q p=0.55) with a similar estimate of effect (RR 0.78; 95% CI 0.71 to 0.85, p<0.001).- Duration between time of first AF diagnosis and AF ablation is associated with an increased likelihood of ablation procedural success. Additional study is required to confirm these results and to explore implementation of earlier catheter AF ablation and patient outcomes within the current AF care pathway.



Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print
Chew DS, Black-Maier E, Loring Z, Noseworthy PA, ... Mark DB, Piccini JP
Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print | PMID: 32191539
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Abstract

Relation of Fractionated Atrial Potentials with the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation during Cardioneuroablation.

Pachon-M EI, Pachon-Mateos JC, Higuti C, Santillana-P TG, ... Silva RF, Guimarães OT

- Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic vagal denervation through endocardial RF ablation for these cases. Main challenges are neuro-myocardium interface identification and the denervation control and validation. The finding that the AF-Nest (AFN) ablation eliminates the atropine response and decreases RR variability suggests that they are related to the vagal innervation.- Prospective, controlled, longitudinal, non-randomized study enrolling 62 patients in two groups: AFN group (AFNG-32 patients) with functional or reflex bradyarrhythmias or vagal AF treated with AFN ablation, and a control group (CG-30 patients) with anomalous bundles, ventricular premature beats, atrial flutter, AV-nodal reentry and atrial tachycardia, treated with conventional ablation (non-AFN ablation). In AFNG, ablation delivered at AFN detected by fragmentation/fractionation of the endocardial electrograms and by 3D anatomical location of the ganglionated plexus. Vagal response was evaluated before, during, and post-ablation by 5s non-contact vagal stimulation at the jugular foramen, through the internal jugular veins (ECVS), analyzing 15s mean heart rate, longest RR, pauses, and AV block. All patients had current guidelines arrhythmia ablation indication.- Pre-ablation ECVS induced sinus pauses, asystole and transient AV block in both groups showing a strong vagal response (=0.96). Post-ablation ECVS in the AFNG showed complete abolishment of the cardiac vagal response in all cases (Pre/post-ablation ECVS=<0.0001), demonstrating robust vagal denervation. However, in the CG, vagal response remained practically unchanged post-ablation (=0.35) showing that non-AFN ablation promotes no significant denervation.- AF-Nest ablation causes significant vagal denervation. Non-AF-Nest ablation causes no significant vagal denervation. These results suggest that AF-Nests are intrinsically related to vagal innervation. ECVS was fundamental to stepwise vagal denervation validation during cardioneuroablation.



Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print
Pachon-M EI, Pachon-Mateos JC, Higuti C, Santillana-P TG, ... Silva RF, Guimarães OT
Circ Arrhythm Electrophysiol: 18 Mar 2020; epub ahead of print | PMID: 32188285
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Abstract

Impact of Cardiac Resynchronization Therapy on Heart Transplant-Free Survival in Pediatric and Congenital Heart Disease Patients.

Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM

- Cardiac resynchronization therapy (CRT) studies in pediatric and/or congenital heart disease (CHD) patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and CHD patients, using a propensity score-matched analysis.- This single-center study compared CRT patients (implant date 2004-2017) and controls, matched by 1:1 propensity-score matching (PSM) using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years or had CHD; had systemic ventricular ejection fraction <;45%; symptomatic heart failure; and had significant electrical dyssynchrony, all prior to CRT implant. Controls were screened from non-selective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period.- Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. 133 controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio 0.24 [95% CI 0.12-0.46], p<0.001). There was no CRT procedural mortality and one system infection at 54 months post-implant.- In pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival.



Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print
Chubb H, Rosenthal DN, Almond CS, Ceresnak SR, ... McElhinney DB, Dubin AM
Circ Arrhythm Electrophysiol: 21 Mar 2020; epub ahead of print | PMID: 32202126
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Abstract

Balance Between Rapid Delayed Rectifier K Current and Late Na Current on Ventricular Repolarization: An Effective Antiarrhythmic Target?

Hegyi B, Chen-Izu Y, Izu LT, Rajamani S, ... Bers DM, Bányász T

- Rapid delayed rectifier K current (I) and late Na current (I) significantly shape the cardiac action potential (AP). Changes in their magnitudes can cause either long or short QT syndromes (LQT, SQT) associated with malignant ventricular arrhythmias and sudden cardiac death.- Physiological self AP-clamp was used to measure I and I during the AP in rabbit and porcine ventricular cardiomyocytes in order to test our hypothesis that the balance between I and I affects repolarization stability in health and disease conditions.- We found comparable amount of net charge carried by I and I during the physiological AP suggesting that outward K current via I and inward Na current via I are in balance during physiological repolarization. Remarkably, I and I integrals in each control myocyte were highly correlated in both healthy rabbit and pig myocytes, despite high overall cell-to-cell variability. This close correlation was lost in heart failure myocytes from both species. Pretreatment with E-4031 to block I (mimicking LQT2) or with ATX-II to impair Na channel inactivation (mimicking LQT3) prolonged APD; however, using GS-967 to inhibit I sufficiently restored APD to control in both cases. Importantly, I inhibition significantly reduced the beat-to-beat and short-term variabilities of APD. Moreover, I inhibition also restored APD and repolarization stability in heart failure. Conversely, pretreatment with GS-967 shortened APD (mimicking SQT), and E-4031 reverted APD shortening. Furthermore, the amplitude of AP alternans occurring at high pacing frequency was decreased by I inhibition, increased by I inhibition, and restored by combined I and I inhibitions.- Our data demonstrate that I and I are counterbalancing currents during the physiological ventricular AP and their integrals co-vary in individual myocytes. Targeting these ionic currents to normalize their balance may have significant therapeutic potential in heart diseases with repolarization abnormalities.



Circ Arrhythm Electrophysiol: 22 Mar 2020; epub ahead of print
Hegyi B, Chen-Izu Y, Izu LT, Rajamani S, ... Bers DM, Bányász T
Circ Arrhythm Electrophysiol: 22 Mar 2020; epub ahead of print | PMID: 32202931
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This program is still in alpha version.