Comparison of electrical dyssynchrony parameters between electrocardiographic imaging and a simulated ECG belt.

AIMS: Electrocardiographic imaging (ECGi) and the ECG belt are body surface potential mapping systems which can assess electrical dyssynchrony in patients undergoing cardiac resynchronization therapy (CRT). ECGi-derived dyssynchrony metrics are calculated from reconstructed epicardial potentials based on body surface potentials combined with a thoracic CT scan, while the ECG belt relies on body surface potentials alone. The relationship between dyssynchrony metrics from these two systems is unknown. In this study we aim to compare intra-ventricular and inter-ventricular dyssynchrony metrics between ECGi and the ECG belt. METHODS: Seventeen patients underwent ECGi after CRT. A subsample of 40 body surface potentials was used to simulate the ECG belt. ECGi dyssynchrony metrics, calculated from reconstructed epicardial potentials, and ECG belt dyssynchrony metrics, calculated from the sampled body surface potentials were compared. RESULTS: There was a strong positive correlation between ECGi left ventricular activation time (LVAT) and ECG belt left thorax activation time (LTAT) (R = 0.88 ; P < 0.001) and between ECGi standard deviation of activation times (SDAT) and ECG belt-SDAT (R = 0.76; P < 0.001) during intrinsic rhythm. The correlation for both pairs was also strong during biventricular pacing. Ventricular electrical uncoupling, a well validated ECGi inter-ventricular dyssynchrony metric, correlated strongly with ECG belt-SDAT during intrinsic rhythm (R = 0.76; P < 0.001) but not biventricular pacing (R = 0.29; P = 0.26). Cranial or caudal displacement of the simulated ECG belt did not affect LTAT or SDAT. CONCLUSION: ECGi- and ECG belt-derived intra-ventricular and inter-ventricular dyssynchrony metrics were strongly correlated. The ECG belt may offer comparable dyssynchrony assessment to ECGi, with associated practical and cost advantages.

Impact of Mg2+ and Al3+ Substitutions on the Structural and Electrochemical Properties of NASICON-Nax VMn0.75 M0.25 (PO4 )3 (M = Mg and Al) Cathodes for Sodium-Ion Batteries.

Sodium superionic conductor (NASICON)-Na4 VMn(PO4 )3 (NVMP) cathode is attractive for sodium-ion battery application due to its reduced cost and toxicity, and high energy density (≈425 Wh kg-1 ). However, it exhibits significant polarization, limited rate and cycling performances due to its lower electronic conductivity and formation of Jahn-Teller active Mn3+ during cycling. In this report, a chemical approach is presented to partially replace Mn2+ of the NVMP framework by Mg2+ and Al3+ substitutions. The Mg- and Al-substituted NVMP cathodes present smoother voltage profiles, facile sodium (de)intercalation, enhanced rate performances (80 mA h g-1 at 5C rate) and capacity retention (≈96% after 100 cycles) in comparison with the unsubstituted sample. Their enhanced performances are attributed to suppressed Jahn-Teller effect, increased covalent character and sodium ion vacancies of the NASICON framework. These results highlight the significance of fine tuning the chemical compositions to attain high performance NASICON cathodes.

The ECG Belt for CRT response trial: Design and clinical protocol.

The ECG Belt for CRT response trial is designed to test the hypothesis that in patients traditionally less likely to respond to cardiac resynchronization therapy (CRT), an individualized approach utilizing the electrocardiogram (ECG) Belt to guide lead placement, vector selection, and device programming is superior to current standard of care. The ECG Belt is a noninvasive mapping technology designed to measure beat by beat electrical activation of the left ventricle by utilizing unipolar measurements from multiple ECG electrodes on the body surface. The ECG Belt for CRT response trial is a multicenter, prospective, randomized, investigational pre-market research study conducted at 48 centers in the United States, Canada, and Europe and will randomize approximately 400 subjects. The trial has three arms (enrollment will be 2:1:1, respectively): utilization of the Belt to guide implant as well as postimplant programming, utilizing the Belt to guide postimplant programming alone, and a non-Belt control arm. AdaptivCRT will be an option in the treatment arm but not the control arms. The primary endpoint is change in left ventricular end-systolic volume between preimplant and at 6 months. This paper describes the design and analytic plan for the trial.

Body surface activation mapping of electrical dyssynchrony in cardiac resynchronization therapy patients: Potential for optimization.

BACKGROUND: Electrical synchronization is likely improved by cardiac resynchronization therapy (CRT), but is difficult to quantify with 12-lead ECG. We aimed to quantify changes in electrical synchrony and potential for optimization with CRT using a body-surface activation mapping (BSAM) system. METHODS: Standard deviation of activation times (SDAT) was calculated in 94 patients using BSAM at baseline CRT (CRTbl), native, and different CRT configurations. RESULTS: SDAT decreased 20% from native to CRTbl (p<0.01) and an additional 26% (p<0.01) at optimal CRT (CRTopt), the minimal SDAT setting. Patients with LBBB and patients with QRS duration ≥150ms had higher native SDAT and greater decrease with CRTbl (p<0.01); however, the improvement from CRTbl to CRTopt was similar in all four groups (range: 24-28%). CRTopt was achieved with biventricular pacing in 52% and LV-only pacing in 44%. We propose that improved wavefront fusion demonstrated by BSAMs contributed substantially to the improved electrical synchrony. CONCLUSION: Optimization potential is similar regardless of pre-CRT QRS morphology or duration. BSAM could possibly improve CRT response by individualizing device programming to minimize electrical dyssynchrony.

Influence of automatic frequent pace-timing adjustments on effective left ventricular pacing during cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) requires effective left ventricular (LV) pacing (i.e. sufficient energy and appropriate timing to capture). The AdaptivCRT™ (aCRT) algorithm serves to maintain ventricular fusion during LV or biventricular pacing. This function was tested by comparing the morphological consistency of ventricular depolarizations and percentage effective LV pacing in CRT patients randomized to aCRT vs. echo-optimization. METHODS AND RESULTS: Continuous recordings (≥20 h) of unipolar LV electrograms from aCRT (n = 38) and echo-optimized patients (n = 22) were analysed. Morphological consistency was determined by the correlation coefficient between each beat and a template beat. Effective LV pacing of paced beats was assessed by algorithmic analysis of negative initial EGM deflection in each evoked response. The %CRT pacing delivered, %effective LV pacing (i.e. % of paced beats with effective LV pacing), and overall %effective CRT (i.e. product of %CRT pacing and %effective LV pacing) were compared between aCRT and echo-optimized patients. Demographics were similar between groups. The mean correlation coefficient between individual beats and template was greater for aCRT (0.96 ± 0.03 vs. 0.91 ± 0.13, P = 0.07). Although %CRT pacing was similar for aCRT and echo-optimized (median 97.4 vs. 98.6%, P = 0.14), %effective LV pacing was larger for aCRT [99.6%, (99.1%, 99.9%) vs. 94.3%, (24.3%, 99.8%), P=0.03]. For aCRT vs. echo-optimized groups, the proportions of patients with ≥90% effective LV pacing was 92 vs. 55% (P = 0.002), and with ≥90% effective CRT was 79 vs. 45%, respectively (P = 0.018). CONCLUSION: AdaptivCRT™ significantly increased effective LV pacing over echo-optimized CRT.

Automated detection of effective left-ventricular pacing: going beyond percentage pacing counters.

AIMS: Cardiac resynchronization therapy (CRT) devices report percentage pacing as a diagnostic but cannot determine the effectiveness of each paced beat in capturing left-ventricular (LV) myocardium. Reasons for ineffective LV pacing include improper timing (i.e. pseudofusion) or inadequate pacing output. Device-based determination of effective LV pacing may facilitate optimization of CRT response. METHODS AND RESULTS: Effective capture at the LV cathode results in a negative deflection (QS or QS-r morphology) on a unipolar electrogram (EGM). Morphological features of LV cathode-RV coil EGMs were analysed to develop a device-based automatic algorithm, which classified each paced beat as effective or ineffective LV pacing. The algorithm was validated using acute data from 28 CRT-defibrillator patients. Effective LV pacing and pseudofusion was simulated by pacing at various AV delays. Loss of LV capture was simulated by RV-only pacing. The algorithm always classified LV or biventricular (BV) pacing with AV delays ≤60% of patient's intrinsic AV delay as effective pacing. As AV delays increased, the percentage of beats classified as effective LV pacing decreased. Algorithm results were compared against a classification truth based on correlation coefficients between paced QRS complexes and intrinsic rhythm QRS templates from three surface ECG leads. An average correlation >0.9 defined a classification truth of ineffective pacing. Compared against the classification truth, the algorithm correctly classified 98.2% (3240/3300) effective LV pacing beats, 75.8% (561/740) of pseudofusion beats, and 100% (540/540) of beats with loss of LV capture. CONCLUSION: A device-based algorithm for beat-by-beat monitoring of effective LV pacing is feasible.

Non-invasive assessment of ventricular electrical heterogeneity to optimize left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a novel therapeutic option for bradycardia and heart failure patients. ECG belt is a novel technology for assessment of ventricular electrical heterogeneity (VEH) using multi-electrode ECG. A metric of overall VEH based on standard deviation of activation times (SDAT) from all electrodes in the ECG belt has been previously shown to predict cardiac resynchronization therapy (CRT) response. The aim of the study is to evaluate non-invasive assessment of VEH using ECG belt to optimize LBBAP. METHODS: VEH from a 40-electrode ECG belt was characterized in 20 patients (male 15, EF 33 ± 13%, NYHA class 3.05 ± 0.6; CRT indication 18) during LBBAP (20) and LBBAP-Optimized CRT (LOT-CRT-7), anodal capture (16), NS-LBBP (18), S-LBBP (5), LVSP (9). In addition to SDAT, regional (LV/RV) VEH was assessed with average left ventricular activation times (LVAT), SDAT of left-sided (LV dispersion) and right-sided (RV dispersion) electrodes. Optimal LBBAP was determined based on maximal SDAT and QRS duration (d) change. RESULTS: All metrics were significantly reduced (p < 0.0001 for ECG belt metrics, p = 0.0027 for QRSd) during LBBAP and LOT-CRT compared to intrinsic. QRSd, SDAT, LVAT, and LV and RV dispersion during optimal LBBAP were significantly lower (133 ± 20/157 ± 24; 20.5 ± 7.5/38.6 ± 9; 44.4 ± 14.3/61.4 ± 21; 11.6 ± 11.6/29.5 ± 15; 21.1 ± 7.8/42.5 ± 9.3; p < 0.0001) compared to intrinsic rhythm. However, they were not significantly different among selective, non-selective, anodal, and LV septal captures. EF and NYHA class improved to 46 ± 11% and 1.9 ± 0.6 (p < 0.001). CONCLUSIONS: LBBAP significantly reduced overall and regional (RV/LV) VEH, irrespective of the mechanism of capture. Detailed assessment of electrical heterogeneity using ECG belt may add valuable insights on effects of LBBAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04583709.

Electrocardiogram Belt guidance for left ventricular lead placement and biventricular pacing optimization.

BACKGROUND: Patients with ischemic cardiomyopathy, non-left bundle branch block, or QRS duration <150 ms have a lower response rate to cardiac resynchronization therapy (CRT) than did other indicated patients. The ECG Belt system (EBS) is a novel surface mapping system designed to measure electrical dyssynchrony via the standard deviation of the activation times of the left ventricle. OBJECTIVES: The objectives of this study were to evaluate the efficacy of the EBS in patients less likely to respond to CRT and to determine whether EBS use in lead placement guidance and device programming was superior to standard CRT care. METHODS: This was a prospective randomized trial of patients with heart failure and EBS-guided CRT implantation and programming vs standard CRT care. The primary end point was relative change in left ventricular end-systolic volume from baseline to 6 months postimplantation. RESULTS: A total of 408 patients from centers in Europe and North America were randomized. Although both patients with EBS and control patients had a mean improvement in left ventricular end-systolic volume, there was no significant difference in relative change from baseline (P = .26). While patients with a higher baseline standard deviation of the activation times derived greater left ventricular reverse remodeling, improvement in electrical dyssynchrony did not correlate with the extent of reverse remodeling. CONCLUSION: The findings of the present study do not support EBS-guided therapy for CRT management of heart failure with reduced ejection fraction.

Design, molecular docking, drug-likeness, and molecular dynamics studies of 1,2,4-trioxane derivatives as novel Plasmodium falciparum falcipain-2 (FP-2) inhibitors.

Despite significant progress made in drug discovery and development over the past few decades, malaria remains a life-threatening infectious disease across the globe. Because of the widespread emergence of drug-resistant strains of Plasmodium falciparum, the clinical utility of existing drug therapies including Artemisinin-based Combination Therapies (ACTs) in the treatment of malaria has been increasingly limited. It has become a serious health concern which, therefore, necessitates the development of novel drug molecules and/or alternative therapies to combat, particularly resistant P. falciparum. The objective of the present study was to develop 1,2,4-trioxane derivatives as novel antimalarial agents that would be effective against resistant P. falciparum. In our study, 15 new trioxane derivatives were designed by molecular modification of the 1,2,4-trioxane scaffold as possible antimalarial agents. Molecular modeling studies of trioxane derivatives were performed based on the CADD approach using Biovia Discovery Studio (DS) 2018 software. The protein-ligand docking study was performed against P. falciparum falcipain 2 (FP-2) using the simulation-based docking protocol LibDock by the flexible docking method. The assessment of drug-likeness, ADMET properties, and toxicity was also performed. Furthermore, the compounds CC3 and CC7, which showed the best binding affinity against the target P. falciparum FP-2, were investigated by molecular dynamics (MD) simulation studies followed by the calculation of MM-PBSA binding free energy of protein-ligand complexes using DS 2020. Results of the docking study showed that among the 15 compounds, three trioxane derivatives were found to possess promising binding affinity with LibDock scores ranging from 117.16 to 116.90. Drug-likeness, ADMET, and toxicity properties were found to be satisfactory for all the compounds. Among the 15 compounds, two compounds, namely CC3 and CC7, showed the highest binding affinity against FP-2 with LibDock score of 117.166 and 117.200, respectively. The Libdock score of the co-crystal inhibitor was 114.474. MD studies along with MM-PBSA calculations of binding energies further confirmed the antimalarial potential of the compounds CC3 and CC7, with the formation of well-defined and stable receptor-ligand interactions against the P. falciparum FP-2 enzyme. Additionally, the selectivity of trioxane hits identified as potential inhibitors of P. falciparum cysteine protease FP-2 was determined on human cysteine proteases such as cathepsins (Cat K and Cat L), which are host homologous. Finally, it was concluded that the newly designed 1,2,4-trioxane derivatives can be further studied for in vitro and in vivo antimalarial activities for their possible development as potent antimalarial agents effective against resistant P. falciparum.

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated. OBJECTIVES: The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients. METHODS: Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax). RESULTS: As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 µVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 µVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 µVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing. CONCLUSIONS: LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.

Cardiac memory in patients with Wolff-Parkinson-White syndrome: noninvasive imaging of activation and repolarization before and after catheter ablation.

BACKGROUND: Cardiac memory refers to a change in ventricular repolarization induced by and persisting for minutes to months after cessation of a period of altered ventricular activation (eg, resulting from pacing or preexcitation in patients with Wolff-Parkinson-White syndrome). ECG imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. METHODS AND RESULTS: Fourteen pediatric patients with Wolff-Parkinson-White syndrome and no other congenital disease, were imaged with ECGI a day before and 45 minutes, 1 week, and 1 month after successful catheter ablation. ECGI determined that preexcitation sites were consistent with sites of successful ablation in all cases to within a 1-hour arc of each atrioventricular annulus. In the preexcited rhythm, activation-recovery interval (ARI) was the longest (349+/-6 ms) in the area of preexcitation leading to high average base-to-apex ARI dispersion of 95+/-9 ms (normal is approximately 40 ms). The ARI dispersion remained the same 45 minutes after ablation, although the activation sequence was restored to normal. ARI dispersion was still high (79+/-9 ms) 1 week later and returned to normal (45+/-6 ms) 1 month after ablation. CONCLUSIONS: The study demonstrates that ECGI can noninvasively localize ventricular insertion sites of accessory pathways to guide ablation and evaluate its outcome in pediatric patients with Wolff-Parkinson-White syndrome. Wolff-Parkinson-White is associated with high ARI dispersion in the preexcited rhythm that persists after ablation and gradually returns to normal over a period of 1 month, demonstrating the presence of cardiac memory. The 1-month time course is consistent with transcriptional reprogramming and remodeling of ion channels.

Hypertrophic cardiomyopathy with preexcitation: insights from noninvasive electrocardiographic imaging (ECGI) and catheter mapping.

UNLABELLED: Hypertrophic Cardiomyopathy and Preexcitation. INTRODUCTION: Fasciculoventricular pathway has been described as an unusual variant of preexcitation. Electrocardiographic imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. CASE: We present a case of an 18-year-old male with hypertrophic cardiomyopathy (HCM) and an electrocardiogram (ECG)-based diagnosis of Wolff-Parkinson-White (WPW) syndrome, who underwent a noninvasive ECGI study to image ventricular activation, followed by an electrophysiology study (EPS). The ECGI electroanatomic isochrone map showed early activation of the epicardial aspect of the atrioventricular (A-V) groove and an aberrant posterior-base-to-apex progression of activation in the left ventricular (LV) epicardium. The EPS showed a likely fasciculoventricular pathway (FVP) without any inducible tachycardia. CONCLUSION: While FVP has been described before, this is the first report of detailed quantitative three-dimensional characterization of electrical activation sequence of a heart with this type of preexcitation, using a novel noninvasive imaging modality (ECGI). In spite of abnormal ventricular activation, the EPS demonstrated that the FVP is not capable of supporting reentrant supraventricular tachycardia or rapidly conducted atrial fibrillation.

Twelve-Lead ECG Optimization of Cardiac Resynchronization Therapy in Patients With and Without Delayed Enhancement on Cardiac Magnetic Resonance Imaging.

Background Delayed enhancement ( DE ) on magnetic resonance imaging is associated with ventricular arrhythmias, adverse events, and worse left ventricular mechanics. We investigated the impact of DE on cardiac resynchronization therapy ( CRT ) outcomes and the effect of CRT optimization. Methods and Results We studied 130 patients with ejection fraction ( EF ) ≤40% and QRS ≥120 ms, contrast cardiac magnetic resonance imaging, and both pre- and 1-year post- CRT echocardiograms. Sixty-three (48%) patients did not have routine optimization of CRT . The remaining patients were optimized for wavefront fusion by 12-lead ECG . The primary end point in this study was change in EF following CRT . To investigate the association between electrical dyssynchrony and EF outcomes, the standard deviation of activation times from body-surface mapping was calculated during native conduction and selected device settings in 52 of the optimized patients. Patients had no DE (n=45), midwall septal stripe (n=30), or scar (n=55). Patients without DE had better ∆ EF (13±10 versus 4±10 units; P<0.01). Optimized patients had greater ∆ EF in midwall stripe (2±9 versus 12±12 units; P=0.01) and scar (0±7 versus 5±10; P=0.04) groups, but not in the no- DE group. Patients without DE had greater native standard deviation of activation times ( P=0.03) and greater ∆standard deviation of activation times with standard programming ( P=0.01). Device optimization reduced standard deviation of activation times only in patients with DE ( P<0.01). Conclusions DE on magnetic resonance imaging is associated with worse EF outcomes following CRT . Device optimization is associated with improved EF and reduced electrical dyssynchrony in patients with DE .

A novel algorithm increases the delivery of effective cardiac resynchronization therapy during atrial fibrillation: The CRTee randomized crossover trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) requires a high percentage of ventricular pacing (%Vp) to maximize its clinical benefits. Atrial fibrillation (AF) has been shown to reduce %Vp in CRT due to competition with irregular intrinsic atrioventricular (AV) conduction. We report the results of a prospective randomized crossover trial evaluating the amount of effective CRT delivered during AF with a novel algorithm (eCRTAF). OBJECTIVE: The purpose of this study was to determine whether eCRTAF increases the amount of effective CRT delivered during AF compared to a currently available rate regularization algorithm. METHODS: Patients previously implanted with a cardiac resynchronization therapy-defibrillator and with a history of AF and intact AV conduction received up to 4 weeks of control (Conducted AF Response) and up to 4 weeks of eCRTAF in a randomized sequence. The percent effective CRT (%eCRT) pacing, which excludes beats without left ventricular capture, %Vp, and mean heart rate (HR) were recorded during AF and sinus rhythm. RESULTS: The eCRTAF algorithm resulted in a significantly higher %eCRT during AF than control (87.8% ± 7.8% vs 80.8% ± 14.3%; P <.001) and %Vp during AF than control (90.0% ± 5.9% vs 83.2% ± 11.9%; P <.001), with a small but statistically significant increase in mean HR of 2.5 bpm (79.5 ± 9.7 bpm vs 77.0 ± 9.9 bpm; P <.001). CONCLUSION: In a cohort of CRT patients with a history of AF, eCRTAF significantly increased %eCRT pacing and %Vp during AF with a small increase in mean HR. This algorithm may represent a novel noninvasive method of significantly increasing effective CRT delivery during AF, potentially improving CRT response.

Changes in electrical dyssynchrony by body surface mapping predict left ventricular remodeling in patients with cardiac resynchronization therapy.

BACKGROUND: Electrical activation is important in cardiac resynchronization therapy (CRT) response. Standard electrocardiographic analysis may not accurately reflect the heterogeneity of electrical activation. OBJECTIVE: We compared changes in left ventricular size and function after CRT to native electrical dyssynchrony and its change during pacing. METHODS: Body surface isochronal maps using 53 anterior and posterior electrodes as well as 12-lead electrocardiograms were acquired after CRT in 66 consecutive patients. Electrical dyssynchrony was quantified using standard deviation of activation times (SDAT). Ejection fraction (EF) and left ventricular end-systolic volume (LVESV) were measured before CRT and at 6 months. Multiple regression evaluated predictors of response. RESULTS: ∆LVESV correlated with ∆SDAT (P = .007), but not with ∆QRS duration (P = .092). Patients with SDAT ≥35 ms had greater increase in EF (13 ± 8 units vs 4 ± 9 units; P < .001) and LVESV (-34% ± 28% vs -13% ± 29%; P = .005). Patients with ≥10% improvement in SDAT had greater ∆EF (11 ± 9 units vs 4 ± 9 units; P = .010) and ∆LVESV (-33% ± 26% vs -6% ± 34%; P = .001). SDAT ≥35 ms predicted ∆EF, while ∆SDAT, sex, and left bundle branch block predicted ∆LVESV. In 34 patients without class I indication for CRT, SDAT ≥35 ms (P = .015) and ∆SDAT ≥10% (P = .032) were the only predictors of ∆EF. CONCLUSION: Body surface mapping of SDAT and its changes predicted CRT response better than did QRS duration. Body surface mapping may potentially improve selection or optimization of CRT patients.

Device pacing diagnostics overestimate effective cardiac resynchronization therapy pacing results of the hOLter for Efficacy analysis of CRT (OLÉ CRT) study.

BACKGROUND: A high percentage of biventricular (BiV) or left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) devices has been associated with superior clinical outcomes. However, the percent ventricular (%V) pacing reported by CRT devices simply indicates the number of paces the device has delivered and not the proportion of pacing that has captured the LV effectively. OBJECTIVE: The purpose of this study was to determine whether a beat-by-beat evaluation of effective pacing would provide a more accurate evaluation of CRT delivery. METHODS: An automatic electrogram (EGM)-based algorithm that classifies each LV pace as effective or ineffective based on detection of QS/QS-r morphology on the unipolar LV EGM during pacing was developed and validated. LV EGMs that were recorded by 24-hour Holter from 57 CRT patients were postprocessed. The percent effective CRT (%e-CRT) pacing was calculated by dividing the time spent in e-CRT pacing by the total time of the recording. RESULTS: In this CRT cohort, the average %V pacing (94.8% ± 8%) significantly overestimated the %e-CRT pacing (87.5% ± 23%; P <.001). A significant minority of subjects (18%) had a discrepancy of at least 3 percentage points between %V pacing and %e-CRT pacing (mean 39% ± 41%). CONCLUSION: Current device pacing diagnostics overestimate the amount of CRT pacing actually delivered. The new algorithm quantifies ineffective CRT pacing, which enables clinicians to identify patients with this issue and to address the reasons behind suboptimal CRT delivery.

Body surface mapping using an ECG belt to characterize electrical heterogeneity for different left ventricular pacing sites during cardiac resynchronization: Relationship with acute hemodynamic improvement.

BACKGROUND: Electrical heterogeneity (EH) during cardiac resynchronization therapy may vary with different left ventricular (LV) pacing sites. OBJECTIVE: The purpose of this study was to evaluate the relationship between such changes and acute hemodynamic response (AHR). METHODS: Two EH metrics-standard deviation of activation times and mean left thorax activation times-were computed from isochronal maps based on 53-electrode body surface mapping during baseline AAI pacing and biventricular (BiV) pacing from different pacing sites in coronary veins in 40 cardiac resynchronization therapy-indicated patients. AHR at different sites was evaluated by invasive measurement of LV-dp/dtmax at baseline and BiV pacing, along with right ventricular (RV)-LV sensing delays and QRS duration. RESULTS: The site with the greatest combined reduction in standard deviation of activation times and left thorax activation times from baseline to BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of, the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV-LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps had much better accuracy (sensitivity 90%, specificity 80%) for identifying hemodynamically responsive sites (∆LV dp/dtmax ≥10%) compared with RV-LV delay (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based on EH metrics showed significant correlation (R2 = 0.53, P <.001) between predicted and measured AHR. CONCLUSION: Changes in EH from baseline to BiV pacing more accurately identified hemodynamically optimal sites than RV-LV delays or paced QRS shortening. Optimization of LV lead location by minimizing EH during BiV pacing, based on body surface mapping, may improve CRT response.

Electrophysiologic substrate and intraventricular left ventricular dyssynchrony in nonischemic heart failure patients undergoing cardiac resynchronization therapy.

BACKGROUND: Electrocardiographic imaging (ECGI) is a method for noninvasive epicardial electrophysiologic mapping. ECGI previously has been used to characterize the electrophysiologic substrate and electrical synchrony in a very heterogeneous group of patients with varying degrees of coronary disease and ischemic cardiomyopathy. OBJECTIVE: The purpose of this study was to characterize the left ventricular electrophysiologic substrate and electrical dyssynchrony using ECGI in a homogeneous group of nonischemic cardiomyopathy patients who were previously implanted with a cardiac resynchronization therapy (CRT) device. METHODS: ECGI was performed during different rhythms in 25 patients by programming their devices to biventricular pacing, single-chamber (left ventricular or right ventricular) pacing, and native rhythm. The electrical dyssynchrony index (ED) was computed as the standard deviation of activation times at 500 sites on the LV epicardium. RESULTS: In all patients, native rhythm activation was characterized by lines of conduction block in a region with steep activation-recovery interval (ARI) gradients between the epicardial aspect of the septum and LV lateral wall. A native QRS duration (QRSd) >130 ms was associated with high ED (≥30 ms), whereas QRSd <130 ms was associated with minimal (25 ms) to large (40 ms) ED. CRT responders had very high dyssynchrony (ED = 35.5 ± 3.9 ms) in native rhythm, which was significantly lowered (ED = 23.2 ± 4.4 ms) during CRT. All four nonresponders in the study did not show significant difference in ED between native and CRT rhythms. CONCLUSION: The electrophysiologic substrate in nonischemic cardiomyopathy is consistent among all patients, with steep ARI gradients co-localizing with conduction block lines between the epicardial aspect of the septum and the LV lateral wall. QRSd wider than 130 ms is indicative of substantial LV electrical dyssynchrony; however, among patients with QRSd <130 ms, LV dyssynchrony may vary widely.