Changes in electrical dyssynchrony by body surface mapping predict left ventricular remodeling in patients with cardiac resynchronization therapy Ryan M. Gage, MS,* Antonia E. Curtin, MS,† Kevin V. Burns, PhD,* Subham Ghosh, PhD,‡ Jeffrey M. Gillberg, MS,‡ Alan J. Bank, MD*† From the *United Heart & Vascular Clinic, St. Paul, Minnesota, †University of Minnesota, Minneapolis, Minnesota, and ‡Medtronic plc, Mounds View, Minnesota. 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.
increase in EF (13 ± 8 units vs 4 ± 9 units; P o .001) and LVESV (−34% ± 28% vs −13% ± 29%; P ¼ .005). Patients with ≥10% improvement in SDAT had greater ΔEF (11 ± 9 units vs 4 ± 9 units; P ¼ .010) and ΔLVESV (−33% ± 26% vs −6% ± 34%; P ¼ .001). SDAT ≥35 ms predicted ΔEF, while ΔSDAT, sex, and left bundle branch block predicted ΔLVESV. In 34 patients without class I indication for CRT, SDAT ≥35 ms (P ¼ .015) and ΔSDAT ≥10% (P ¼ .032) were the only predictors of ΔEF.
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.
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.
RESULTS ΔLVESV correlated with ΔSDAT (P ¼ .007), but not with ΔQRS duration (P ¼ .092). Patients with SDAT ≥35 ms had greater
(Heart Rhythm 2017;14:392–399) I 2016 Heart Rhythm Society. All rights reserved.
Introduction
randomized trial to report changes in QRSd with CRT pacing and found that this was not an independent outcome predictor. However, smaller single- or dual-center studies have reported conflicting results on QRSd reduction and response to therapy in LBBB patients.5–7 Two investigations performed by Ploux and colleagues8,9 assessed the ability of body surface mapping to predict acute hemodynamic and 6-month clinical response after CRT. Their high-resolution methodology used 252 electrodes, which overlaid onto a patient-specific computed tomography (CT) scan, allowed for reconstruction of 1500 epicardial unipolar electrograms. Changes with CRT in electrocardiographic (ECG) mapping metrics of global and regional LV electrical dyssynchrony correlated well with changes in dP/dt max (maximal rate of LV pressure rise).8 In 33 CRT patients with QRSd ≥120 ms and LBBB or nonspecific interventricular conduction delay (NSIVCD), an ECG mapping index of electrical dyssynchrony was a better predictor of response than was QRSd or LBBB.9 We have developed a noninvasive body surface mapping technology that uses a 53-electrode belt placed over the
Cardiac resynchronization therapy (CRT) improves symptoms, functional capacity, and left ventricular (LV) size and function in selected heart failure (HF) patients. Traditionally, patients with depressed systolic function, wide QRS duration (QRSd), and left bundle branch block (LBBB) respond best to CRT.1,2 Despite technology improvements such as quadripolar LV leads and automated adaptive pacing algorithms,3 at least 25% of patients do not respond. Likely causes of nonresponse include insufficient electrical dyssynchrony pre-CRT or persistent electrical dyssynchrony post-CRT. The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction Study4 is the only major
This work was supported by a grant through the Medtronic External Research Program, Medtronic plc. Mr Gage, Ms Curtin, Dr Burns, and Dr Bank have received grant and consulting payments from Medtronic. Dr Ghosh and Mr Gillberg are employees of Medtronic. Address reprint requests and correspondence: Dr Alan J. Bank, United Heart & Vascular Clinic, 225 N Smith Avenue, Suite 400, St. Paul, MN55102. E-mail address:
[email protected].
1547-5271/$-see front matter B 2016 Heart Rhythm Society. All rights reserved.
KEYWORDS Cardiac resynchronization therapy; Heart failure; Response; Electrocardiography; Body surface mapping
http://dx.doi.org/10.1016/j.hrthm.2016.11.019
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chest and upper back and does not require imaging studies. Unipolar electrograms produce isochronal activation maps reflecting high-level patterns of spatial propagation of activation as reflected on the body surface. Quantitative metrics of electrical dyssynchrony are derived from these maps. Standard deviation of activation times (SDAT) and average left thorax activation time (LTAT) are computed on the basis of isochronal times. Using this technology during CRT implantation, we demonstrated that changes in these electrical dyssynchrony metrics have substantially better sensitivity and specificity at predicting acute hemodynamic response (LV dP/dtmax) than native right ventricular (RV)– LV sensing delay (surrogate of “Q-LV”) or QRSd changes with pacing. In 88% of patients, the pacing location with the greatest reduction in ECG belt dyssynchrony with CRT corresponded to the hemodynamically optimal site.10 The objective of the present study was to test the hypothesis that changes in electrical dyssynchrony with CRT, as quantified by a 53-electrode ECG belt, predict changes in LV size and function 6 months after CRT. In addition, we hypothesized that body surface mapping indices of electrical dyssynchrony would provide better predictive value than would standard 12-lead ECG measures.
Methods Study population Consecutive consenting patients at United Heart & Vascular Clinic (St. Paul, MN) receiving a de novo CRT device, without concurrent atrioventricular (AV) nodal ablation, between May 9th 2014 and November 25th 2015 were studied. Inclusion criteria included ejection fraction (EF) ≤40% and New York Heart Association class II–IV (ambulatory) HF on optimal medical therapy. Patients were implanted with LV pacing leads targeting lateral/posterolateral veins. The CRT programmed setting was selected for each subject on the basis of 12-lead ECG wavefront fusion6,11 1week post-CRT, which is our standard procedure. Standard ECGs were acquired over a range of V-V offsets from V-V simultaneous (0 ms) to LV ahead by 60 ms. If native AV conduction was present, ECGs of LV-only pacing fused with right bundle branch conduction were acquired at different AV delays, often ranging from 50% to 80% of the native PR interval. Fusion was identified by narrowing of the QRSd and/ or presence of the R wave in leads V1/V2. Patients without ≥90% ventricular pacing at 6 months were excluded. Class I indication for CRT was defined as QRSd ≥150 ms and LBBB.12 Written informed consent was obtained, and the protocol was approved by an institutional review board.
Twelve-lead ECG LBBB was defined as notched or broad slurred R waves in leads I and V5/V6 and rS or QS pattern in leads V1/V2. Right bundle branch block (RBBB) was defined as rsrʹ, rsRʹ, or rSRʹ morphology in leads V1/V2 and deep S waves in leads V5/V6. NSIVCD included patients without LBBB or RBBB. Native ECGs were analyzed for rhythm, PR and QRS
393 intervals, and QRS morphology before CRT, and ~1 week postimplantation. To determine the ΔQRS width after CRT, the global interval method13 was used with rhythm strips magnified 400%.
ECG belt A single-use disposable ECG belt (Verathon Inc, Bothell, WA, and modified by Medtronic plc, Mounds View, MN) with 17 anterior and 36 posterior unipolar ECG electrodes was placed ~1 week postimplantation. An ECG amplifier and a storage unit (Verathon Inc) were used with off-line custom postprocessing software written in Matlab (version 7.0, MathWorks, Inc., Natick, MA). Activation time of each unipolar electrogram was defined as the time to the steepest negative slope, and colorcoded isochronal activation maps were produced. Electrical dyssynchrony was quantified as the SDAT from all electrodes.
Pacing protocol Device interrogation noting arrhythmia burden, percent atrial and ventricular pacing, and programming parameters was performed. The ECG belt data were collected at baseline programmed (12-lead ECG–optimized) CRT setting and with CRT off (native). RV-only pacing replaced native rhythm if patients were symptomatic without ventricular support or were upgraded to CRT from a device with a high percentage of RV pacing.
Echocardiography Echocardiograms were acquired before CRT and ~6 months post-CRT with commercially available systems. LV enddiastolic and end-systolic volumes (LVESV) and EF were measured using biplane Simpson’s method. Radial intraventricular mechanical dyssynchrony was measured (Tom Tec, Version 4.6, Untershleissheine, Germany) on mid-LV short-axis images with a radial opposing wall delay ≥130 ms considered significant.14
Statistical analysis Continuous variables are presented as mean ± SD and categorical variables as counts (percentages). The relationships between electrical and echocardiographic characteristics were assessed using Pearson correlation coefficients. Differences in continuous variables at 2 time points were compared using paired Student t tests. Univariate linear regression analysis was performed to relate potential predictors to EF and LVESV changes at 6 months. These predictors were evaluated with a stepwise multiple regression model using backward elimination until all variables in the model had P o .10. STATA/SE software (version 12.1, StataCorp, College Station, TX) was used, with a 2-tailed P o .05 considered significant.
Results Study population The 66 patients studied (Table 1) were 70 ± 11 years old, with an EF of 27% ± 7% on standard medical therapy.
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Table 1 Baseline demographic and clinical characteristics of the patients (N ¼ 66). Characteristic
Value
Age (y) Sex: male NYHA class II/III Ischemic etiology Permanent AF β-Blocker ACEI/ARB PR interval (ms) QRS duration (ms) QRS morphology LBBB RBBB NSIVCD RV paced RV lead Apical Septal LV lead Anterolateral Lateral Posterolateral Posterior LVESV (mL) LVEDV (mL) EF (%) Radial opposing wall delay (ms)
70 ± 11 44 (67%) 63 (95%) 32 (48%) 6 (9%) 62 (94%) 57 (86%) 193 ± 45 152 ± 26 36 (55%) 3 (5%) 15 (22%) 12 (18%) 16 (24%) 50 (76%) 6 (9%) 43 (65%) 16 (24%) 1 (2%) 120 ± 56 161 ± 62 27 ± 7 190 ± 134
Values are presented as mean ± SD or as count (%). ACEI/ARB ¼ angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker; AF ¼ atrial fibrillation; EF ¼ ejection fraction; LBBB ¼ left bundle branch block; LV ¼ left ventricular; LVEDV ¼ left ventricular enddiastolic volume; LVESV ¼ left ventricular end-systolic volume; NSIVCD ¼ nonspecific interventricular conduction delay; NYHA ¼ New York Heart Association; RBBB ¼ right bundle branch block; RV ¼ right ventricular.
Forty-four (67%) patients were men, and 32 (48%) had ischemic cardiomyopathy. QRSd was 152 ± 26 ms, and QRS morphology was LBBB in 36 (55%) patients. Twelve patients (18%) were pacemaker dependent, so RV pacing was considered the underlying condition instead of native. Native SDAT was 37 ± 11 ms with a median of 36.5 ms. RV leads were most commonly implanted in the septum (n=50, 76%), and coronary sinus LV leads (n=50, 76% quadripolar) were implanted in anterolateral (n=6, 9%), lateral (n=43, 65%), posterolateral (n=16, 24%), or posterior (n=1, 2%) locations. From implantation to ECG vest mapping (10 ± 3 days), patients were paced with Medtronic’s AdaptivCRT Algorithm (n=29, 44%) or at the implanter’s recommendations (n=37, 56%). Those without AdaptivCRT often had standard CRT programming with V-V simultaneous (89%) and AV delay (67% ± 13% of the native PR interval). Over 6 months of follow-up, 23 patients (35%) received pacing via Medtronic’s AdaptivCRT Algorithm (16 predominantly LVonly pacing and 7 predominantly biventricular pacing). The 43 patients without AdaptivCRT were manually programmed on the basis of 12-lead ECG wavefront fusion to the following: V-V simultaneous (47%), LV preexcited (35%), RV preexcited (2%), and LV only (16%).
Figure 1 Classical ECG belt map representations of QRS morphologies. Anterior and posterior ECG belt maps are shown along with QRS duration and SDAT for patients with different 12-lead ECG QRS morphologies (see text for descriptions). ECG ¼ electrocardiographic; LBBB ¼ left bundle branch block; NSIVCD ¼ nonspecific interventricular conduction delay; RBBB ¼ right bundle branch block; SDAT ¼ standard deviation of activation time.
ECG belt maps Figure 1 shows intrinsic activation maps from 6 patients. In the normal subject, there is near-simultaneous propagation of activation with low SDAT. In the HF patient (pre-CRT EF 21%) with narrow QRS complex, there is a mild delay in posterior electrode activation and a higher SDAT. In the LBBB patient, activation of most (or all) of the posterior map is delayed with a high SDAT. Conversely, in the patient with RBBB most of the anterior map exhibits delayed activation. The patient with NSIVCD has a heterogeneous activation pattern. Based on observations such as these, and more detailed studies of body surface ECG mapping with ECG imaging methodology,15 the majority of the anterior activation map likely represents the RV and the majority of the posterior map the LV, although perhaps variable with heart orientation. Figure 2 shows a Bland-Altman plot of 96 SDAT measurements of electrical dyssynchrony in 59 patients
Figure 2 Bland-Altman plot of SDAT reproducibility. SDAT measurements (n ¼ 96) were made ~20 minutes apart at a given condition (native, baseline programmed, or V-V offset other than baseline) using the same electrocardiographic belt. SDAT ¼ standard deviation of activation time.
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Figure 3 Relationship between QRSd and SDAT. Under native but not CRT conditions, QRSd and SDAT (A) are modestly correlated. ΔQRSd and ΔSDAT are also correlated (B). CRT ¼ cardiac resynchronization therapy; QRSd ¼ QRS duration; SDAT ¼ standard deviation of activation time.
under the same condition assessed ~20 minutes apart using the same ECG belt. The average difference of −0.5 ± 3 ms between the 2 measures of SDAT was not significantly different from 0 (P ¼ .127), and the 95% limits of agreement were −6.3 to 5.4 ms. Figure 3 shows the relationship between measures of electrical dyssynchrony quantified by 12-lead ECG (QRSd) and ECG belt (SDAT) under native conduction and programmed CRT (Figure 3A). There is a modest correlation between SDAT and QRSd under native (r ¼ 0.57; P o .0001) but not programmed (r ¼ 0.20; P ¼ .131) conditions. There is also a modest but weaker correlation between ΔQRSd and ΔSDAT post-CRT (Figure 3B).
Echocardiography outcomes and measures of electrical dyssynchrony After CRT, EF significantly increased by 9 ± 10 units (P o .001) and LVESV significantly decreased by 26% ± 30% (P o .001). Echocardiographic response was high: 69% with ≥15% reduction in LVESV and 65% with EF increase ≥5 absolute units. Figure 4A shows correlations between ΔSDAT and ΔLVESV at 6 months. ΔSDAT correlated with ΔLVESV (r ¼ 0.34; P ¼ .007) and ΔEF
(r ¼ −0.26; P ¼ .039) (graph not shown). The correlation between ΔQRSd and ΔLVESV was not significant (Figure 4B). Activation maps from 4 patients with CRT off and CRT at 12-lead ECG–optimized CRT programming are shown in Figure 5. In these patients, large increases in SDAT and LVESV occurred without corresponding reductions in QRSd. Figure 6A shows ΔEF and ΔLVESV for groups categorized by traditional predictors of CRT response and ECG belt metrics. Patients with native SDAT ≥35 ms vs those without had a significantly greater ΔEF (13 ± 8 units vs 4 ± 9 units; P o .001) and ΔLVESV (−34% ± 28% vs −13% ± 29%; P ¼ .005). Patients with ≥10% increase in SDAT also had a significantly greater increase in EF (11 ± 9 units vs 4 ± 9 units; P ¼ .010) and decrease in LVESV (−33% ± 26% vs −6% ± 34%; P ¼ .001). LBBB and QRSd ≥150 ms, but not mechanical dyssynchrony or ΔQRSd ≥10%, predicted improved echocardiographic CRT response. Table 2 shows LV functional and remodeling response in patients grouped by native SDAT (≥35 ms or not) and ΔSDAT (≥10% increase or not). Nearly all (36 of 38) patients with native SDAT ≥35 ms improved SDAT ≥10%. Patients with native SDAT o35 ms were nearly equally divided between SDAT improving ≥10% (15 of 28) and o10% (13 of 28).
Figure 4 Echocardiographic outcomes related to SDAT and QRSd changes with CRT. Correlation between ΔSDAT and ΔLVESV after CRT (A). ΔSDAT significantly correlated with ΔLVESV. However, ΔQRSd did not correlate with ΔLVESV (B). CRT ¼ cardiac resynchronization therapy; LVESV ¼ left ventricular end-systolic volume; QRSd ¼ QRS duration; SDAT ¼ standard deviation of activation time.
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Figure 5 Electrocardiographic belt and echocardiographic outcome examples by QRS morphology. Patients with different native QRS morphologies who had large changes in LVESV and SDAT with minimal changes in QRSd. ESV ¼ end-systolic volume; CRT ¼ cardiac resynchronization therapy; IVCD ¼ interventricular conduction delay; LBBB ¼ left bundle branch block; QRSd ¼ QRS duration; RBBB ¼ right bundle branch block; RV ¼ right ventricular; SDAT ¼ standard deviation of activation time.
Figure 6B shows echocardiographic outcomes in a subgroup of 34 patients without class I indication of LBBB and QRSd ≥150 ms (previously RV-paced patients excluded). In this subgroup, EF response differences occurred only in groups with native SDAT ≥35 ms (13 ± 8 units vs 4 ± 9 units; P ¼ .015) and SDAT improving ≥10% (9 ± 11 units vs 2 ± 7 units; P ¼ .032). Only the SDAT improving ≥10% group showed significantly greater LVESV reverse remodeling (−27% ± 32% vs −3% ± 34%; P ¼ .049). LBBB, radial mechanical dyssynchrony, and QRSd reduction ≥10% did not predict CRT response. Table 3 shows univariate linear regression relating common predictors of CRT response to ΔEF and ΔLVESV. ECG belt metrics (native SDAT ≥35 ms and SDAT reduction ≥10%) significantly predicted both ΔEF and ΔLVESV. LBBB significantly predicted both echocardiographic outcomes, but no other baseline characteristic, including sex, HF etiology, native QRSd ≥150 ms, or QRSd reduction ≥10%, significantly predicted both ΔEF and ΔLVESV. In a multiple regression model using backward stepwise elimination, native SDAT ≥35 ms was the only significant predictor of ΔEF while SDAT reduction ≥10%, sex, and LBBB were significant predictors of ΔLVESV.
Discussion We describe a new noninvasive body surface mapping technology for generating isochronal maps depicting highlevel spatial patterns of cardiac activation. A metric of electrical dyssynchrony (SDAT) derived from the maps quantified the heterogeneity of electrical activation. This technology can be used to reproducibly measure electrical dyssynchrony before and after CRT. We demonstrate that SDAT correlates modestly with QRSd during native rhythm, but not during CRT pacing. In addition, ΔSDAT correlates with ΔLVESV and is a better predictor of LV functional and reverse remodeling response (in all patients and in a subset of patients without class I indication for CRT) than baseline ECG characteristics (QRS morphology or QRSd) or changes in ECG metrics with CRT such as QRSd narrowing.
Measurement of electrical dyssynchrony The 12-lead ECG has been the only widely available clinical tool to assess electrical dyssynchrony. QRSd and QRS morphology have been used for patient selection in all studies of CRT. However, these are measured using a limited number of leads that may not capture the entire activation process. Furthermore, QRSd, although used as a “surrogate” of electrical dyssynchrony, is a 1-dimensional temporal index that provides limited insight into the underlying electrical heterogeneity, which depends on how activation times of different regions of the heart are related. Body surface isochronal mapping offers a more in-depth view of spatial distribution of activation during depolarization. We demonstrate in this study that while QRSd correlates modestly with SDAT under native rhythm, there is a wide range of SDAT values for any given QRSd. In addition, paced QRSd does not correlate with paced SDAT. Change in QRSd with CRT has not been helpful in assessing electrical dyssynchrony improvement with CRT.4 Analysis of QRS morphology changes with CRT, indicating fusion of the activation wavefronts, has been proposed as a potential response predictor, although that analysis applied only to LBBB patients.6 In our study, ΔQRSd did not correlate with ΔSDAT after CRT. Many patients had marked improvement in activation maps, SDAT, and LV remodeling after CRT placement without major changes on the 12-lead ECG. These observations suggest that ECG belt measurement of electrical dyssynchrony is more sensitive to changes by CRT than is QRSd. Noninvasive ECG imaging techniques using CT scans of the heart provide high-resolution epicardial activation maps.8,9 Our technology similarly maps cardiac electrical activation but uses body surface potentials alone to generate maps and quantify electrical dyssynchrony, using fewer electrodes, and avoiding the need for CT scans. Although this technique does not project cardiac potentials onto the epicardium, the information is sufficiently detailed to detect reproducible changes in activation maps and SDAT that occur post-CRT.
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Figure 6 Echocardiographic outcomes by baseline characteristics and 1-week changes with CRT. EF and LVESV outcomes for the entire patient cohort (A) and for patients without class I indication for CRT (B) dichotomized by baseline pre-CRT characteristics (left of red line) and changes with CRT (right of red line). CRT ¼ cardiac resynchronization therapy; EF ¼ ejection fraction; LVESV ¼ left ventricular end-systolic volume.
We have shown that acute hemodynamic response to CRT correlates well with changes in 2 ECG belt measures of electrical dyssynchrony: SDAT and LTAT.10 In that study, the largest hemodynamic improvements occurred when there were large increases in both SDAT and LTAT. In the present
study we analyzed only a single measure (SDAT) of global electrical dyssynchrony. However, when using this methodology for other purposes (such as CRT optimization), LTAT or other measures of electrical dyssynchrony obtained from the ECG belt may be helpful.
398 Table 2
Heart Rhythm, Vol 14, No 3, March 2017 LV functional and remodeling response by native SDAT and ΔSDAT with CRT.
Variable
Native SDAT o35 ms
Native SDAT ≥35 ms
SDAT improved o10%
n ¼ 15 (23%) ΔEF (units) ¼ 2 ± 7 ΔLVESV (%) ¼ −8 ± 25 n ¼ 13 (20%) ΔEF (units) ¼ 6 ± 11 ΔLVESV (%) ¼ −20 ± 34
n ¼ 2 (3%) ΔEF (units) ¼ 16 ± 21 ΔLVESV (%) ¼ 12 ± 92 n ¼ 36 (54%) ΔEF (units) ¼ 12 ± 8 ΔLVESV (%) ¼ −37 ± 22
SDAT improved ≥10%
CRT ¼ cardiac resynchronization therapy; EF ¼ ejection fraction; LV ¼ left ventricular; LVESV ¼ left ventricular end-systolic volume; SDAT ¼ standard deviation of activation time.
Predicting response to CRT Numerous baseline (pre-CRT) variables predict beneficial response to CRT including longer QRSd,1,4 presence of LBBB,2,4 female sex,16,17 nonischemic etiology of HF,7,16 and mechanical dyssynchrony.14,18,19 While these and other baseline variables help predict response to CRT, many patients without one (or many) of these variables still respond to CRT and some patients with one (or many) of these variables do not. Similar to other larger studies, LBBB and wider QRS complex were associated with improved CRT response in our study. However, using univariate regression, native SDAT ≥35 ms was the best predictor of EF response (coefficient 8.6 units; P o .001), whereas a ≥10% decrease in SDAT post-CRT was the best predictor of LVESV response (coefficient −27.4%; P = .001). In multiple regression analysis, SDAT ≥35 ms was the only predictor of EF response while a ≥10% decrease in SDAT, sex, and LBBB predicted LVESV response. Although patients with SDAT o35 ms did not respond as well to CRT as did those with SDAT ≥35 ms, a subset of this group (13 of 28 [46%]) who improved SDAT by ≥10% averaged a 6-unit EF increase and a 20% LVESV reduction (Table 2). Thus, the presence of only mild/moderate electrical dyssynchrony pre-CRT does not necessarily portend a poor CRT response. Moreover, though not reported here, we often identified device settings that produced a lower SDAT compared to 12-lead ECG optimized settings in both groups of patients. On the basis of our finding that ΔSDAT is an important predictor of CRT response, we hypothesize that programming CRT devices to the lowest SDAT would significantly increase response. Our future work will focus on the potential to optimize CRT in all patients using the ECG belt. Table 3
Current class I indication for CRT includes QRS ≥150 ms and LBBB.12 There is considerable debate about the benefits of CRT in patients with QRSd ≥120 ms without class I indication. Improved patient selection for CRT in this population is needed. Over half the patients in our study did not have class I indication for CRT. In this group, SDAT significantly predicted increase in EF, whereas LBBB and radial dyssynchrony did not (Figure 6B). In patients without class I indication, the only baseline measure associated with a significantly greater EF response was native SDAT ≥35 ms. Unlike QRSd reduction ≥10%, SDAT reduction ≥10% was a significant predictor of EF and LVESV response. Although ΔSDAT can only be determined with pacing, and thus cannot be used for CRT patient selection, the lack of increase in SDAT with CRT can alert clinicians to the need for further interventions such as changes in programming (possibly guided by ECG belt), lead revision, or consideration of advanced HF therapies in appropriate candidates.
Study limitations Our sample size is larger than any previous body surface mapping studies evaluating chronic CRT response, but is still only modest. We did not compare our activation maps against a criterion standard such as ECG imaging (using more electrodes and CT scans). Our study end point did not include clinical outcomes, but LV reverse remodeling at 6 months is predictive of long-term clinical outcomes in CRT patients.20 We acquired activation maps and SDAT values at a variety of different CRT settings, but did not use these data to try and optimize programming. Programmed CRT settings were quite variable with 35% of patients programmed to LVonly pacing by either the AdaptivCRT algorithm or 12-lead
Univariate predictors of echocardiographic response at 6 months post-CRT (all patients). ΔEF (units)
ΔLVESV (%)
Characteristic
Coefficient
95% CI
P
Coefficient
95% CI
P
Male sex Ischemic etiology LBBB Native QRS ≥150 ms Native SDAT ≥35 ms ≥10% decrease in QRSd ≥10% decrease in SDAT
−3.8 −2.1 6.3 5.7 8.6 2.5 6.8
−8.7 −6.8 0.9 1.1 4.3 −2.5 1.7
.132 .369 .023 .015 o.001 .318 .010
18.7 11.0 −24.0 −13.3 −21.2 −13.2 −27.4
3.2 −4.0 −42.2 −28.3 −35.8 −29.2 −43.3
.019 .148 .011 .081 .005 .104 .001
to 1.2 to 2.6 to 11.7 to 10.2 to 12.9 to 7.6 to 12.0
to 34.3 to 26.1 to 5.8 to 1.7 to −6.5 to 2.8 to 11.6
CRT ¼ cardiac resynchronization therapy; EF ¼ ejection fraction; LBBB ¼ left bundle branch block; LVESV ¼ left ventricular end-systolic volume; QRSd ¼ QRS duration; SDAT ¼ standard deviation of activation time.
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ECG optimization. This programming may be different from that found in the average CRT patient, but reflects increasing evidence of the benefit of appropriately timed LV-only pacing. This aggressive programming is consistent with the greater increase in EF (of 9 units) in our population. Future analyses are planned to assess optimization potential and to study the effects of ECG belt-guided optimization on echocardiographic and clinical outcomes in CRT patients.
399
8.
9.
10.
Conclusion Body surface mapping using the ECG belt allows the measurement of electrical synchrony before and after CRT. ECG belt change in electrical synchrony (ΔSDAT), but not ΔQRSd, correlates with improvement in LV structure and function after CRT. Native SDAT and ΔSDAT predict echocardiographic response to CRT better than traditional measures of response in both our total patient group and in those without class I indication for CRT. ECG belt electrical dyssynchrony information could potentially be used to improve CRT patient selection and optimization.
11.
12.
13.
14.
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