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 .

QRS Complex Detection and Measurement Algorithms for Multichannel ECGs in Cardiac Resynchronization Therapy Patients.

We developed an automated approach for QRS complex detection and QRS duration (QRSd) measurement that can effectively analyze multichannel electrocardiograms (MECGs) acquired during abnormal conduction and pacing in heart failure and cardiac resynchronization therapy (CRT) patients to enable the use of MECGs to characterize cardiac activation in such patients. The algorithms use MECGs acquired with a custom 53-electrode investigational body surface mapping system and were validated using previously collected data from 58 CRT patients. An expert cohort analyzed the same data to determine algorithm accuracy and error. The algorithms: 1) detect QRS complexes; 2) identify complexes of the most prevalent morphology and morphologic outliers; and 3) determine the array-specific (i.e., anterior and posterior) and global QRS complex onsets, offsets, and durations for the detected complexes. The QRS complex detection algorithm had a positive predictivity and sensitivity of ≥96% for complex detection and classification. The absolute QRSd error was 17 ± 14 ms, or 12%, for array-specific QRSd and 12 ± 10 ms, or 8%, for global QRSd. The absolute global QRSd error (12 ms) was less than the interobserver variation in that measurement (15 ± 10 ms). The sensitivity, positive predictivity, and error of the algorithms were similar to the values reported for current state-of-the-art algorithms designed for and limited to simpler data sets and conduction patterns and within the variation found in clinical 12-lead ECG QRSd measurement techniques. These new algorithms permit accurate, real-time analysis of QRS complex features in MECGs in patients with conduction disorders and/or pacing.

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.

Left ventricular-only pacing in heart failure patients with normal atrioventricular conduction improves global function and left ventricular regional mechanics compared with biventricular pacing: an adaptive cardiac resynchronization therapy sub-study.

AIMS: Right ventricular (RV) pacing can impair left ventricular (LV) function. When timed with native RV activation, LV-only pacing may cause greater improvements in LV function than biventricular pacing. This study compared the chronic effects of cardiac resynchronization therapy (CRT) on LV mechanics between biventricular pacing and LV-only pacing in patients with normal atrioventricular (AV) conduction. METHODS AND RESULTS: The Adaptive CRT (aCRT) algorithm provides LV-only pacing timed with native RV activation when the AV interval is normal (≤200 ms during sinus rhythm). We studied patients from the aCRT trial with normal AV conduction at their baseline visit and compared changes in cardiac function after 12 months of treatment with conventional biventricular or mostly (≥80%) LV-only pacing. Speckle tracking echocardiography was used to assess LV myocardial strain before and after treatment. Despite similar improvements in Packer's clinical composite scores and LV volumes, LV-only paced patients (n = 70) had a greater improvement in LV ejection fraction (8.5 ± 11.3% vs. 5.5 ± 10.3%, P = 0.038) and global LV radial strain (6.3 ± 8.6% vs. 4.0 ± 10.1%, P = 0.046) than those randomized to biventricular pacing (n = 91). Strain was improved to a greater extent near the RV pacing lead, in septal and apical regions (P < 0.05 for both regions), in patients receiving LV-only pacing. CONCLUSION: In heart failure patients with normal AV conduction, LV-only pacing timed with native RV activation may result in greater improvements in LV ejection fraction and myocardial strain compared with biventricular pacing due to better apical and septal function.

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.

Long-Term Echocardiographic Response to Cardiac Resynchronization Therapy in Initial Nonresponders.

OBJECTIVES: The aim of this study was to investigate the frequency and clinical implications of a delayed echocardiographic response to cardiac resynchronization therapy (CRT). BACKGROUND: Long-term prognosis for CRT patients is routinely based on the assessment of echocardiograms after 6 to 12 months of therapy. Some patients, however, may require a longer period of therapy before echocardiographic improvements are detectable. METHODS: This observational study included all patients with heart failure (HF) receiving a CRT device at a single center from 2003 to 2011. Eligible patients met current indications and had technically adequate echocardiograms from before implantation, approximately 1 year after implantation (mid-term), and ≥3 years after implantation (long-term). A positive echocardiographic response to CRT was defined as a reduction in left ventricular end-systolic volume ≥15%. All-cause mortality was compared for patients in 3 response groups: mid-term responders, long-term responders, and nonresponders. RESULTS: During this study, 294 patients met the study criteria. Of the 120 patients who were nonresponders after 1 year, 52 (43%) experienced a delayed positive response. Delayed, long-term responders had mortality and hospitalization rates similar to mid-term responders and significantly lower than nonresponders. CONCLUSIONS: Among patients surviving at least 3 years after implantation of a CRT device and with echocardiographic follow-up, a significant portion of nonresponders after 1 year of CRT experience a delayed echocardiographic response after a longer period of time. Survival and hospitalization rates were similar for all echocardiographic responders, regardless of the time at which the response occurred.

An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel.

PURPOSE: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. METHODS: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. RESULTS: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. CONCLUSION: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel cross-section and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options.