Intrinsic QRS Duration Research Articles

Electrical Reverse Remodeling of the Native Cardiac Conduction System after Cardiac Resynchronization Therapy.

Background: Little is known about electrical remodeling of the native conduction systems, particularly how the PR interval changes, after cardiac resynchronization therapy (CRT). We investigated the effects of CRT on the intrinsic PR interval (i-PRi) and QRS duration (i-QRSd). Methods and results: In 100 consecutive CRT recipients with sinus rhythm and long-term follow-up (>1 year), the i-PRi and i-QRSd were measured at baseline and at the last echocardiographic follow-up (33.4 ± 17.9 months) with biventricular pacing temporarily withdrawn. The relative decrease in the left ventricular end-systolic volume (LVESV) was measured to define CRT-responders (≥15%) and super-responders (≥30%). Following CRT, the left ventricular (LV) ejection fraction increased significantly (p < 0.001). In CRT-responders (n = 71), the LVESV and i-QRSd decreased markedly (170 ± 39 to 159 ± 24 ms, p = 0.012). However, the i-PRi was not shortened with CRT response and was actually likely to increase, even in the super-responder group (n = 33). Moreover, lengthening of the i-PRi was observed consistently irrespective of the CRT response status, beta-blocker use, or amiodarone use. CRT non-responders were associated with a remarkable PR prolongation (p = 0.005) and QRS widening (p = 0.001), along with positive ventricular remodeling. Conclusion: LV volume and i-QRSd decreased markedly with CRT response. However, the i-PRi was not shortened, but rather increased regardless of the degree of CRT response. CRT non-response was associated with a considerable increase in the i-PRi and i-QRSd, along with positive ventricular remodeling. CRT-induced electrical reverse remodeling might occur preferentially in the intraventricular, but not the atrioventricular, conduction system.

P1496Impact of electrical reverse remodeling by cardiac resynchronization therapy on adverse cardiac events in patients of heart failure with reduced ejection fraction

Abstract Background Recently, structural reverse remodeling (SRR) and electrical reverse remodeling (ERR) after cardiac resynchronization therapy (CRT) have been reported in patients of heart failure with reduced ejection fraction (HFrEF). However the relationship between ERR and subsequent adverse cardiac events is still unknown. We aimed to elucidate the impact of ERR after CRT on the occurrence of heart failure events and ventricular arrhythmias. Methods A total of 36 HFrEF patients who underwent newly CRT implantation were investigated retrospectively. The intrinsic QRS duration (iQRSd) had been recorded before and more than 6 months after CRT implantation. Biventricular pacing was temporarily turned off during measurement of iQRSd. ERR was defined as positive shortening of iQRSd and SRR was defined as reduction of left ventricular end systolic volume by more than 15% after CRT implantation. The primary endpoint was a composite of all cause death, heart failure hospitalizations and ventricular tachyarrhythmia events. Results ERR was observed in 17 patients (47.2%) and SRR in 22 patients (61.1%). The group with ERR included more patients with lower NYHA class prior to CRT and patients with SRR. The primary endpoint was observed in 15 patients (51.4 %) for a median of 181 [63, 367] days during follow-up. Kaplan-Meier analysis revealed that the group without ERR was poor prognosis compared with the group with ERR (p = 0.022, Log-rank test). Conclusion Patients of HFrEF with ERR after CRT may have fewer adverse cardiac events such as worsening heart failure or ventricular arrhythmia events from this short-term study. Abstract Figure. Adverse cardiac events and ERR

862Syncav with multipoint pacing improves acute left ventricular hemodynamics

Abstract Funding Acknowledgements Abbott Introduction SyncAV has been shown to improve electrical synchronization by automatically adjusting atrioventricular delay (AVD) according to the intrinsic atrioventricular conduction time. Additional incremental electrical synchronization may be gained by the addition of second left ventricular (LV) pulse with MultiPoint Pacing (MPP). While the electrical synchronization benefits of SyncAV have been previously explored, there has been no assessment of the acute hemodynamic impact of SyncAV with or without MPP. Objective Evaluate the acute LV hemodynamic impact of SyncAV with and without MPP. Methods Heart failure patients with LBBB and QRS duration (QRSd) &amp;gt; 140 ms undergoing CRT-P/D implant with a quadripolar LV lead were enrolled in this prospective study. A guidewire or catheter with pressure transducer was placed in the LV chamber and the maximum pressure change (dP/dtmax) was recorded during the following pacing modes: intrinsic conduction, conventional biventricular pacing with SyncAV (BiV + SyncAV), and MPP with SyncAV (MPP + SyncAV). Twelve-lead surface ECG was used to determine the patient-tailored SyncAV offset that minimized QRSd. Results Twenty-seven patients (67% male, 44% ischemic, 30 ± 7% ejection fraction) completed the acute recordings. Relative to the intrinsic QRSd of 163 ms, BiV + SyncAV reduced QRSd by 21.5% to 124 ms (p &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV reduced QRSd by 26.6% to 120 ms (p &amp;lt; 0.05 vs. BiV + SyncAV). Beyond electrical synchronization, SyncAV significantly improved acute hemodynamics. Relative to the intrinsic dP/dtmax of 842 mmHg/s, BiV + SyncAV elevated dP/dtmax by 6.3% to 900 mmHg/s (p &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV elevated dP/dtmax by 8.8% to 926 mmHg/s (p &amp;lt; 0.005 vs. BiV + SyncAV). Despite both QRSd and dP/dtmax improvement with SyncAV and MPP, correlation between electrical and hemodynamic measurements was poor (R2 = 0.0 for BiV + SyncAV, R2 = 0.1 for MPP + SyncAV). Conclusion SyncAV may significantly improve acute LV hemodynamics in addition to electrical synchrony in LBBB patients. Further incremental improvement was achieved by combining SyncAV with MPP. Abstract Figure.

43Dynamic atrioventricular delay achieves superior electrical synchrony when pacing both ventricles rather than left ventricle alone

Abstract Funding Acknowledgements Abbott Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization when pacing one or two sites in the left ventricle together with the right ventricle. However, it is unknown if the same benefit can be gained by using SyncAV while pacing only the left ventricle without right ventricular pacing. Purpose Evaluate the acute improvement in electrical synchrony provided by SyncAV with and without MultiPoint Pacing (MPP) during biventricular (BiV) and LV only pacing. Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. QRSd was measured post-implant from 12-lead surface electrograms by blinded experts during the following pacing configurations: intrinsic conduction, conventional BiV (BiV = RV + LV1), MPP (MPP = RV + LV1 + LV2), LV-only single-site (LVSS = LV1 only), and LV-only MPP (LVMPP = LV1 + LV2). For each pacing mode, SyncAV was enabled (e.g. BiV + SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. As an additional reference, QRSd during BiV was also measured using the nominal static AVD (paced/sensed AVD = 140/110 ms). BiV and LVSS pacing used the latest activating LV cathode, whereas MPP and LVMPP used the two LV cathodes with the widest possible separation (&amp;gt;30mm). All configurations used the minimum programmable RV-LV and LV1-LV2 delays. Results Thirty-five patients (78% male, 33% ischemic, 26% ejection fraction, 165 ms intrinsic QRSd) completed device implant and QRSd assessment. Relative to intrinsic conduction, BiV with nominal AVD reduced the QRSd by 17.5% (p &amp;lt; 0.001 vs intrinsic). Enabling SyncAV with a patient-optimized offset significantly improved QRSd reduction. BiV + SyncAV reduced QRSd by 25.2% (p &amp;lt; 0.001 vs. BiV). The greatest QRSd reduction of 28.9% was achieved by MPP + SyncAV (p &amp;lt; 0.01 vs. BiV + SyncAV). Single- and multi-site LV-only pacing reduced QRSd significantly less than corresponding biventricular modes. LVSS + SyncAV reduced QRSd by 22.5% (p &amp;lt; 0.05 vs. BiV + SyncAV), and LVMPP + SyncAV reduced QRSd by 24.3% (p &amp;lt; 0.05 vs. MPP + SyncAV). As a percent of PR interval, optimal SyncAV offsets were similar for BiV + SyncAV (median: 13%, mean: 17%) vs. MPP + SyncAV (median: 13%, mean 16%, p = 0.35 vs. BiV + SyncAV), and similar for LVSS + SyncAV (median: 20%, mean: 28%) and LVMPP + SyncAV (median: 23%, mean: 26%, p = 0.35 vs. LVSS + SyncAV), but were significantly higher for LV-only settings vs. corresponding BiV/MPP settings (p &amp;lt; 0.01 for both pairs). Conclusion: Greater improvement in electrical synchrony using SyncAV was observed when right ventricular pacing was included with left ventricular pacing. Additional benefit was gained by the addition of a second left ventricular pacing site with MPP in combination with SyncAV in both biventricular and LV only pacing modes. Abstract Figure.

863Leadless endocardial pacing improves symptoms in patients with failed conventional CRT implant in long term follow up

Abstract Funding Acknowledgements EBR Systems, Inc OnBehalf WiSE-CRT and LV-SELECT study and POST-M REGISTRY Background The WiSE-CRT (Wireless stimulation endocardial) system has advantages over conventional epicardial CRT. Whenever conventional CRT failed to implant or failed to echocardiographic response, the WiSE-CRT was implanted as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) over the last 8 years. All these studies have reported high rates of clinical and echocardiographic response compared to conventional CRT. Objectives The purpose of this analysis was to determine the safety and clinical response in the largest available number of implanted patients (pts) with long term follow up of 2 years and the first, second and third generation of WiSE-CRT devices. Method All pts undergoing a WiSE-CRT implantation as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) were analysed (N = 165). Pts were followed-up for 24 months and considered CRT responders if an improvement in NYHA ≥ 1 class from baseline (pre-implant) was achieved. Results In total, 165 pts were implanted, demographics include: 68.2 ± 9.6 year’s old, 81.8% male, 49.7% with history of AFib and 54.5% non-ischaemic aetiology. The mean intrinsic QRS duration was 165.0 ± 32.3 msec (28 pts pace-maker dependent). 161 pts had the system successfully implanted with no major complications, 3 (1.8%) pts developed a pericardial effusion and 1 (0.6%) electrode was lost during implantation and recovered surgically. During the 24-month follow-up period, 20 (12.1%) pts died from any cause, 4 (2.4%) pts developed TIA or Stroke and 15 (9.1%) pts had pocket or transmitter infection. There was a significant improvement in NYHA functional class in 63.6% pts and an average improvement of -26.1 (-45.1, -7.1) msec in QRS duration. Conclusion Despite a history of failed conventional CRT implantation, pts undergoing CRT upgrades with a WiSE-CRT have a high success rate and a complication rate similar to previously described. In addition endocardial LV pacing led to symptomatic improvements in 64% of patients reaching the 24 month of follow up. Abstract Figure 1: Forest Plot NYHA Responder Rat

Leadless left ventricular endocardial pacing in nonresponders to conventional cardiac resynchronization therapy.

Endocardial pacing may be beneficial in patients who fail to improve following conventional epicardial cardiac resynchronization therapy (CRT). The potential to pace anywhere inside the left ventricle thus avoiding myocardial scar and targeting the latest activating segments may be particularly important. The WiSE-CRT system (EBR systems, Sunnyvale, CA) reliably produces wireless, endocardial left ventricular (LV) pacing. The purpose of this analysis was to determine whether this system improved symptoms or led to LV remodeling in patients who were nonresponders to conventional CRT. An international, multicenter registry of patients who were nonresponders to conventional CRT and underwent implantation with the WiSE-CRT system was collected. Twenty-two patients were included; 20 patients underwent successful implantation with confirmation of endocardial biventricular pacing and in 2 patients, there was a failure of electrode capture. Eighteen patients proceeded to 6-month follow-up; endocardial pacing resulted in a significant reduction in QRS duration compared with intrinsic QRS duration (26.6 ± 24.4ms; P=.002) and improvement in left ventricular ejection fraction (LVEF) (4.7 ± 7.9%; P=.021). The mean reduction in left ventricular end-diastolic volume was 8.3 ± 42.3 cm3 (P=.458) and left ventricular end-systolic volume (LVESV) was 13.1 ± 44.3 cm3 (P=.271), which were statistically nonsignificant. Overall, 55.6% of patients had improvement in their clinical composite score and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%. Nonresponders to conventional CRT have few remaining treatment options. We have shown in this high-risk patient group that the WiSE-CRT system results in improvement in their clinical composite scores and leads to LV remodeling.

Influence of baseline QRS on the left ventricular ejection fraction recovery after frequent premature ventricular complex ablation

Frequent premature ventricular complexes (PVCs) can induce or worsen left ventricular systolic dysfunction. We aimed to investigate the influence of the baseline QRS in the response after PVC ablation in patients with depressed left ventricular ejection fraction (LVEF). Two hundred and fifteen [59 ± 13 years old, 152 (71%) men] consecutive patients with left ventricular (LV) systolic dysfunction and frequent PVCs referred for ablation were included and followed-up for 12 months. Echocardiographic response was defined as an improvement of at least five absolute points in LVEF. Clinical, electrocardiogram, and electrophysiological characteristics were analysed. Mean baseline QRS duration was 110 ms [97-140]. Premature ventricular complex burden significantly decreased after ablation from 23% [16-33] at baseline to 1% [0-8] at 12 months, P < 0.001. Mean PVC burden reduction was 18 [8-30] points. There was a significant improvement of LVEF from 35% [29-40] at baseline to 44% [35-55] at 12 months, P < 0.001. One hundred and thirty (61%) patients were considered as echocardiographic responders. Baseline QRS duration (ms) [odds ratio (OR) 0.98 (0.97-0.99), P = 0.01] was an independent predictor of echocardiographic response. Mean LVEF improvement was 16 [10-21] points when the baseline QRS duration was <90 ms; 12 [4-20] when it was 90-110 ms; 5 [0-15] when it was 110 ± 130 ms; and 0 [0-6] points when it was >130 ms. In patients with LV systolic dysfunction, intrinsic QRS duration is inversely related to the probability and the degree of echocardiographic response after frequent PVC ablation. Patients with a QRS duration >130 ms at baseline have the poorer response after ablation.

Cardiac electrical and mechanical synchrony of super-responders to cardiac resynchronization therapy.

BackgroundSuper-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs.MethodsWe retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging.ResultsSeventeen SRs were included with LV ejection fraction increased from 33.0 ± 4.6% to 59.3 ± 6.3%. The intrinsic QRS duration after super-response was 148.8 ± 30.0 ms, significantly shorter than baseline (174.8 ± 11.9 ms, P = 0.004, t = −3.379) but longer than BIV-paced level (135.5 ± 16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ± 16.5° vs. 19.8 ± 8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ± 64.2° vs. 60.5 ± 22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ± 8.1° vs. 15.2 ± 6.4°, P = 0.005, t = 3.414; PHB, 60.5 ± 22.9° vs. 46.0 ± 16.3°, P = 0.009, t = 3.136).ConclusionsSRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

The European Society of Cardiology Cardiac Resynchronization Therapy Survey II: A comparison of cardiac resynchronization therapy implantation practice in Europe and France

The first European Cardiac Resynchronization Therapy (CRT) Survey, conducted in 2008-2009, showed considerable variations in guideline adherence and implantation practice. A second prospective survey (CRT Survey II) was then performed to describe contemporary clinical practice regarding CRT among 42 European countries. To compare the characteristics of French CRT recipients with the overall European population of CRT Survey II. Demographic and procedural data from French centres recruiting all consecutive patients undergoing either de novo CRT implantation or an upgrade to a CRT system were collected and compared with data from the European population. A total of 11,088 patients were enrolled in CRT Survey II, 754 of whom were recruited in France. French patients were older (44.7% aged≥75 years vs 31.1% in the European group), had less severe heart failure symptoms, a higher baseline left ventricular ejection fraction and fewer co-morbidities. Additionally, French patients had a shorter intrinsic QRS duration (19.1% had a QRS<130ms vs 12.3% in the European cohort). Successful implantation rates were similar, but procedural and fluoroscopy times were shorter in France. French patients were more likely to receive a CRT pacemaker than European patients overall. Of note, antibiotic prophylaxis was reported to be administered less frequently in France, and a higher rate of early device-related infection was observed. Importantly, French patients were less likely to receive optimal drugs for treating heart failure at hospital discharge. This study highlights contemporary clinical practice in France, and describes substantial differences in patient selection, implantation procedure and outcomes compared with the other European countries participating in CRT Survey II.

Deep Negative Deflection in Unipolar His-Bundle Electrogram as a Predictor of Excellent His-Bundle Pacing Threshold Postimplant.

Background His-bundle pacing (HBP) is a physiological form of pacing. Although high capture thresholds are common, few predictors of low HBP threshold have been determined. We aimed to identify electrophysiological predictors. Methods Fifty-one patients (53% with atrioventricular block) underwent HBP for bradycardia with an intrinsic QRS duration of <120 ms. Attempts to anchor the HBP lead were guided by unipolar His-bundle electrograms (HB EGMs) recorded with an electrophysiology recording system. Patients were followed-up for >6 months. Results In total, 153 attempts at anchoring the HBP lead were made, of which, 45 achieved acceptable HBP thresholds (≤2.5 V at 1 ms). The amplitude of negative deflection in HB EGM and the selective HBP form at fixation were independently associated with achieving an acceptable threshold. A negative amplitude of ≥0.060 mV in HB EGM was determined as the optimal value for identifying the acceptable threshold. This deep negative HB EGM was recorded with an HBP threshold of 1.4±1.3 V (in 34 attempts), significantly lower than that of positive HB EGM without deep negative deflection (2.8±1.3 V, in 31 trials; or >5 V, in 38 trials). The permanent HBP lead remained with deep negative (≥0.060 mV) or positive HB EGMs in 28 and 14 patients, respectively, and with positive or negative HB injury current in 19 and 23 patients, respectively. During follow-up, increased HBP threshold of >1 V was significantly more prevalent in the positive HB EGM group. The HBP thresholds of deep negative HB EGM and HB injury current, but not of the selective HBP group, were significantly lower than the other subgroups during follow-up. Conclusions Deep negative HB EGM at fixation was associated with an excellent short-term HBP threshold, similar to HB injury current. Analysis of unipolar HB EGM postfixation may enable prediction of permanent HBP threshold.

Permanent left bundle branch area pacing for atrioventricular block: Feasibility, safety, and acute effect

Left bundle branch area pacing (LBBAP), a new pacing approach, lacks adequate evaluation. To assess the feasibility, safety, and acute effect of permanent LBBAP in patients with atrioventricular block (AVB). A total of 33 AVB patients with indications for ventricular pacing were recruited. Electrocardiograms, pacing parameters, echocardiographic measurements, and complications associated with LBBAP were evaluated perioperatively and at 3-month follow-up. Successful LBBAP was defined as a paced QRS morphology of right bundle branch block pattern in lead V1 and QRS duration (QRSd) less than 130 ms. LBBAP was successfully performed in 90.9% (30/33) of patients (mean age: 55.1 ± 18.5 years; 66.7% male). The mean capture threshold was similar during the procedure (0.76 ± 0.26 V at 0.4 ms) and at the 3-month follow-up (0.64 ± 0.20 V at 0.4 ms). The paced QRSd was 112.8 ± 10.9 ms during the procedure and 116.8 ± 10.4 ms at the 3-month follow-up. Baseline left or right bundle branch block was corrected (intrinsic QRSd 153.3 ± 27.8 ms vs paced QRSd 122.2 ± 9.9 ms) with a success rate of 68.7% (11/16). One ventricular septal lead perforation occurred soon after the procedure with characteristics of pacing failure, and lead revision was successful. Cardiac function and left ventricular synchronization by 2-dimensional echocardiographic strain imaging at the 3-month follow-up slightly improved compared with that at baseline. Permanent LBBAP yielded a stable threshold, a narrow QRSd, and preserved left ventricular synchrony with few complications. Our preliminary results indicate that LBBAP holds promise as an attractive physiological pacing strategy for AVB.

Dynamic programming of atrioventricular delay improves electrical synchrony in a multicenter cardiac resynchronization therapy study

Patient-specific programming of cardiac resynchronization therapy (CRT) is often neglected, despite significant nonresponse rates. The device-based SyncAV CRT algorithm dynamically adjusts atrioventricular delays to the intrinsic AV interval, reduced by a programmable offset, to accommodate each patient's changing needs. The purpose of this study was to evaluate the acute effect of biventricular (BiV) pacing enhanced by SyncAV on electrical synchrony in a broad patient population. Patients with existing CRT implants were prospectively evaluated at 5 international centers. Blinded 12-lead electrocardiographic QRS duration (QRSd) measurements were used to compare intrinsic conduction with nominal BiV pacing, BiV + SyncAV (default 50 ms offset), and BiV + SyncAV (optimized, patient-specific offset). BiV configurations were tested twice using the latest activating and earliest activating left ventricular (LV) electrodes as cathodes. Ninety patients (mean age 67.1 ± 9.5 years; 67 (74%) men; 55 (63%) with left bundle branch block; 37 (43%) with ischemic cardiomyopathy; LV ejection fraction 32% ± 9%) with intact atrioventricular conduction (PR interval 195 ± 45 ms) were enrolled. With BiV pacing from the latest activating LV electrode, the intrinsic QRSd of 155 ± 29 ms was reduced by 9% ± 20% to 138 ± 27 ms using traditional BiV pacing and by 13% ± 14% to 133 ± 25 ms using BiV + SyncAV (50 ms offset). The maximal QRSd reduction by 20% ± 10% to 123 ± 22 ms was achieved by BiV + SyncAV with an optimized offset. Similar QRSd reductions were observed with BiV pacing from the earliest activating LV electrode across all settings. Of all baseline characteristics, intrinsic QRSd was the only significant predictor of QRSd reduction magnitude. SyncAV improved acute electrical synchrony beyond conventional CRT, particularly with patient-specific optimization. The degree of synchrony restored was contingent on intrinsic QRSd, but not limited by other baseline characteristics or by the LV pacing electrode used.

Reproducibility of measuring QRS duration and implications for optimization of interventricular pacing delay in cardiac resynchronization therapy.

QRS narrowing after CRT is a predictor of patient outcome. Further narrowing can be obtained by interventricular pacing delay (VVd) optimization, raising interest to inter and intraobserver variation in manual measurements of QRS duration. (a) Variation in intrinsic rhythm QRS duration in CRT patients with LBBB: In 40 intrinsic 12-lead ECGs, six observers measured QRS duration defined as widest QRS in any lead. In 20 of these ECGs, two observers repeated the measurements. (b) Variation in paced QRS duration at different VVd settings and agreement in selecting the narrowest QRS: In 20 CRT patients, five paced ECGs were recorded at different VVds. The most frequently selected VVd(s) estimated to cause the narrowest QRS in each patient defined the optimal VVd. Two observers repeated the measurements and VVd selections. Absolute interobserver difference in measured QRS duration in intrinsic rhythm ECGs was mean 2ms, range (-40; 40ms), mean limits of agreement (LoA): -21; 25ms. Absolute interobserver difference in measured QRS duration in paced ECGs was mean 3ms, range (-50; 60ms), mean LoA: -20; 27ms. There was no difference in LoA between intrinsic and paced QRS duration (lower limit p=0.68; upper limit p=0.44). The optimal VVd was included in 17/20 (85%) of the VVd selections by six observers. Interobserver variation was comparable with the intraobserver variation. Interobserver variation and intraobserver variation in manually measured paced and intrinsic rhythm QRS duration are clinically acceptable and comparable in a cohort of CRT patients. Inter and intraobserver reproducibility for selecting the optimal VVd is good and warrants manual VVd optimization for QRS narrowing in CRT.

Electrical remodelling post cardiac resynchronization therapy in patients with ischemic and non-ischemic heart failure

BackgroundThe beneficial effects of cardiac resynchronization therapy (CRT) in heart failure are largely considered to be due to improved mechanical contractility. The contributory role of electrical remodelling is less clear. We sought to evaluate the impact of electrical remodelling in these patients. Methods33 patients with conventional indications for CRT and with ischemic (ICM) (n = 17) and non-ischemic (NICM) (n = 16) aetiologies for heart failure were prospectively recruited. Functional parameters of peak exercise oxygen consumption (VO2max) and Minnesota quality of life (QOL) score, echocardiographic measures of LV functions and parameters of electrical remodelling, e.g. intrinsic QRS duration (iQRSD), intracardiac conduction times of LV pacing to RV electrocardiogram (LVp-RVegm), were measured at CRT implant and after 6 months. ResultsOnly two electrical parameters predicted functional or symptomatic improvement. LVp-RVegm reduction significantly correlated with improvement in VO2max (r = −0.42, p = 0.03 while reduction in iQRSD significantly correlated with improvement in QOL score (r = 0.39, p = 0.04). The extent of changes in LVp-RVegm and iQRSD was significantly greater in NICM than in ICM patients (p = 0.017 and p = 0.042 for heterogeneity). There was also significant differential impact on QOL score in the NICM relative to the ICM group (p = 0.003) but none with VO2max. On multivariate analysis, only non-ischemic aetiology was a significant determinant of reduction in iQRSD. ConclusionCRT induces potentially beneficial reduction in LVp-RVegm and iQRSD, which are seen selectively in NICM rather than ICM patients. The extent of improvement in these markers is associated with some functional and symptomatic measures of CRT efficacy.

Effect of QRS Morphology and Duration on Clinical Outcomes After Cardiac Resynchronization Therapy - Analysis of Japanese Multicenter Registry.

QRS duration (QRSd) and morphology are established response predictors of cardiac resynchronization therapy (CRT). However, evidence in Japanese populations is lacking.Methods and Results:We retrospectively analyzed the Japanese multicenter CRT database. We divided patients according to their intrinsic QRSd and morphology, and assessed echocardiographic responses and clinical outcomes. The primary endpoint was a composite of all-cause death or hospitalization because of heart failure. A total of 510 patients were enrolled: 200 (39%) had left bundle branch block (LBBB) and QRSd ≥150 ms; 80 (16%) had LBBB (QRSd: 120-149 ms); 61 (12%) had non-LBBB (NLBBB) (QRSd: ≥150 ms); 54 (11%) had NLBBB (QRSd: 120-149 ms); 115 (23%), narrow (<120 ms). The proportion of echocardiographic responders was higher in LBBB (QRSd ≥150 ms) [74% vs. 51% vs. 38% vs. 52% vs. 50%, LBBB (QRSd ≥150 ms) vs. LBBB (QRSd 120-149 ms) vs. NLBBB (QRSd ≥150 ms) vs. NLBBB (QRSd 120-149 ms) vs. narrow, respectively, P<0.001]. During follow-up (3.2±1.5 years), the incidence of the primary endpoint was lowest in the LBBB group (QRSd ≥150) (28.6% vs. 42.3% vs. 45.9% vs. 55.6% vs. 55.3%, respectively, P<0.001). This difference was still significant after adjusting for other baseline characteristics. In this Japanese patient population, LBBB intrinsic QRS morphology and prolonged QRSd (≥150 ms) exhibited the best response to CRT.

Pressure-Volume Loop Analysis of Multipoint Pacing With a Quadripolar LeftVentricular Lead in Cardiac Resynchronization Therapy.

This study aimed to compare multipoint pacing (MPP) to optimal biventricular pacing with a quadripolar left ventricular (LV) lead and find factors associated with hemodynamic response to MPP. MPP with a quadripolar LV lead may increase response to cardiac resynchronization therapy. Heart failure patients with a left bundle branch block underwent cardiac resynchronization therapy implantation. Q to LV sensing interval divided by the intrinsic QRS duration was measured. Invasive pressure-volume loops were assessed during 4 biventricular pacing settings and 3 MPP settings, using 4 atrioventricular delays. Hemodynamic response was defined as change in stroke work (Δ%SW) compared with baseline measurements during intrinsic conduction. Δ%SW of MPP was compared with conventional biventricular pacing using the distal electrode and the electrode with highest Δ%SW (BIV-OPT). Forty-three patients were analyzed (age 66 ± 10 years, 63% men, 30% ischemic cardiomyopathy, LV ejection fraction 29 ± 8%, and QRS duration 175 ± 13 ms). Q to local LV sensing interval corrected for QRS duration was 84 ± 8%, and variation between LV electrodes was 9 ± 5%. Compared with conventional biventricular pacing using the distal electrode, MPP showed a significant higher increase of SW (Δ%SW+15 ± 35%; p< 0.05) with a large interindividual variation. There was no significant difference in Δ%SW with MPP compared with BIV-OPT (-5 ± 24%; p= 0.19). Male sex and low LV ejection fraction were associated with increase in Δ%SW due to MPP versus BIV-OPT in multivariate analysis, while ischemic cardiomyopathy was only associated in univariate analysis. Optimization of the pacing site of a quadripolar LV lead is more important than to program MPP. However, specific subgroups (i.e., especially men) may benefit substantially from MPP.

Association between reverse electrical remodeling and cardiac fibrosis markers in patients with cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) induces structural and electrical reverse remodeling of the failing heart. However, the association between native QRS narrowing and cardiac fibrosis markers has not been investigated in patients with an implanted CRT device. A total of 41 symptomatic patients diagnosed with systolic heart failure who underwent CRT implantation were included in this study. Electrocardiogram findings and cardiac fibrosis marker levels [galectin-3, growth-differentiation factor-15 (GDF-15) and procollagen III N-terminal propeptide (P3TD)] were collected before and 12 months after initiation of biventricular pacing. Reverse electrical remodeling was defined as a decrease in 12-month intrinsic QRS (iQRS) duration by ≥20 milliseconds after CRT implantation. The median QRS duration decreased from 155 milliseconds (interquartile range [IQR]: 142-178 milliseconds) before CRT to 142 milliseconds (IQR: 130-161 milliseconds) (p=0.001) after 12 months of CRT. According to the predefined criteria, electrical remodeling was detected in 16 (39.0%) patients. The median galectin-3, GDF-15, and P3TD levels were significantly decreased after CRT implantation in patients with electrical remodeling [27.65 ng/mL (IQR: 24.4-35.2 ng/mL) vs 23.00 ng/mL (IQR: 16.0-36.7 ng/mL), p=0.017; 3104 pg/mL (IQR: 2923-4825 pg/mL) vs 2276 pg/mL (IQR: 1294-3209 pg/mL), p=0.002; 0.43 ng/mL (IQR: 0.23-0.64) vs 0.15 ng/mL (IQR: 0.04-0.29 ng/mL), p=0.034, respectively]. The galectin-3, GDF-15, and P3TD levels were not significantly changed in patients without electrical remodeling [26.80 ng/mL (IQR: 23.9-31.5 ng/mL) vs 28.80 ng/mL (IQR: 23.0-34.8 ng/mL), p=0.211; 4221 pg/mL (IQR: 2709-4995 pg/mL) vs 3035 pg/mL (IQR: 2038-4872 pg/mL), p=0.143; and 0.34 ng/mL (IQR: 0.11-0.68 ng/mL) vs 0.21 ng/mL (IQR: 0.09-0.37 ng/mL), p=0.112, respectively]. The results from the small sample used in this study indicated that electrical reverse remodeling after CRT was associated with a decrease in cardiac fibrosis.

96-34: Importance and Difference of Variability of Paced QRS Duration Caused by Right Ventricular Apex Pacing and Septal Pacing in Patients with Atrioventricular Block

Purpose: The variability of paced QRS duration (pQRSd) is sometimes recognized in the clinical situation. The aim of this study was to evaluate the importance of pQRSd and to assess effects of right ventricular septal (RVS) pacing compared with right ventricular apex (RVA) pacing in patients with atrioventricular block (AVB). Method: 181 consecutive new patients with a RV electrode due to high-degree AVB during the period from January 2004 to December 2013 were studied retrospectively. They were observed regularly at pacemaker (PM) clinic during at least 1 year. The sites of RVS were decided by chest X-ray and QRS morphology in II lead of the 12-lead electrocardiogram (ECG) as high septum (HS), mid septum (MS), and low septum (LS). Result: Mean age was 75.1 years and 99 were men. Mean follow-up was 5.2 years and 130 patients had a complete AVB. 77 patients received RVA pacing and 104 received RVS pacing. 153 patients had more than 50% as the percentage of ventricular pacing (%VP). In all patients, the mean pQRSd at PM implanting was 151ms and the mean pQRSd during follow-up period was 155ms. Although there was no significant difference between the intrinsic QRS duration in patients with RVA pacing and that in patients with RVS pacing, the mean pQRSd caused by RVS pacing was significantly narrower than that caused by RVA pacing and the difference had been recognized through an observation period (153ms vs. 159ms, p = 0.029). It needed 4.4 years to get the longest pQRSd on the average (8–4088 days). In patients with more than 50% as %VP, although there was no significant difference of pQRSd among sites in RVS, the rate of change of pQRSd (%pQRSd) caused by HS pacing was higher than that caused by MS and LS pacing (5.06% vs. 2.38%, p = 0.02). Similarly, %pQRSd caused by HS pacing tended to be higher than that caused by RVA pacing, MS and LS pacing (p = 0.059). In patients with ≧50% as %VP, there was no difference in probability of heart failure (HF) hospitalization between patients with RVS pacing and patients with RVA pacing. Furthermore there was no significant difference of the prognosis between patients with ≧150ms as pQRSd and with <150ms, but in patients with left ventricular (LV) dysfunction with LV ejection fraction (EF) less than 40% the probability of HF hospitalization in patients with ≧150ms as pQRSd was significantly worse than that in patients with <150ms (p = 0.04). Moreover, patients with LV dysfunction and prolonged pQRSd, that means %pQRSd was more than 0%, had significantly high provability of HF hospitalization (p = 0.03). On the other hand, each of LV dysfunction and PH affected HF hospitalization regardless of pacing site (p = 0.03 and p = 0.02), although antiarrhythmic agents did not bring any influence prognosis. Conclusion: Each of pacing sites in RV or pQRSd did not any affect on prognosis in patients with AVB. The pQRSd and %pQRSd are important in patients with LV dysfunction, so HS should not be selected in patients with LV dysfunction because HS pacing brings high %pQRSd. And pQRSd changes for a long term, so that it should be observed carefully.

Relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging and cardiac reverse remodeling levels after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) can provide cardiac reverse remodeling (RR), which may include mechanical reverse remodeling (MRR) and/or electrical reverse remodeling (ERR). However, uncoupling of MRR and ERR is not uncommon, and the underlying mechanisms are not clear. This study aimed to evaluate the relationship of myocardial substrate characteristics as assessed by myocardial perfusion imaging (MPI) and cardiac RR post-CRT. Forty-one patients (26 men, mean age 66±10years) with heart failure received CRT for at least 12months were assigned to three groups according to their levels of RR: I, MRR+ERR (ESV reduced ≥15% and intrinsic QRS duration reduced ≥10ms); II, MRR only (ESV reduced ≥15%); and III, non-responder (the others). All the patients also underwent MPI under transient CRT-off to evaluate the intrinsic myocardial substrates, including myocardial scar, LV volumes and function, systolic dyssynchrony, and activation sequences. In addition, ventricular tachycardia (VT) and ventricular fibrillation (VF) detected by the CRT devices during follow-up periods were also recorded. Quantitative analysis of MPI showed that there were significant differences for scar burden [15.9±9.5, 26.8±16.1, and 45.6±15.1% for group I (n=15), II (n=16), and III (n=10), respectively, p<0.001], EDV (136.6±64.9, 221.6±123.9, and 351.8±216.3ml, p=0.002), ESV (82.6±59.8, 172.3±117.2, and 293.3±209.6ml, p=0.001), LVEF (44.9±15.0, 25.6±10.9, and 21.5±11.7%, p<0.001), systolic phase SD (23.4°±10.3°, 36.0°±16.2°, and 57.0°±22.2°, p<0.001), and bandwidth (72.5°±31.1°, 113.4°±56.4°, and 199.1°±90.1°, p<0.001). Myocardial scar interfered with the normal propagation of mechanical activation, resulting in heterogeneous activation sequences. Compared with group II (MRR only), group I (ERR+MRR) had significantly less initial activation segments (1.9±1.0 vs. 2.6±0.7, p<0.05) and shorter maximal contraction delay (46.9°±12.9° vs. 58.8°±18.5°, p<0.05). During the periods of follow-up, 21 patients developed VT/VF, including only 1 patient (1 VT) in group I (6.7%), 8 patients (7 VT and 1 VF) in group II (50%), and 9 patients (7 VT and 5 VF) in group III (90%). The characteristics of myocardial substrates as assessed by MPI differed significantly between different levels of cardiac RR post-CRT. Myocardial scar played an important role in the development of ERR. Different cardiac RR levels contributed to different incidences of ventricular arrhythmia, and the combination of ERR and MRR provided highest anti-arrhythmic effects.

Native Electrocardiographic QRS Duration after Cardiac Resynchronization Therapy: The Impact on Clinical Outcomes and Prognosis

BackgroundWe investigated whether reversed electrical remodeling (RER), defined as narrowing of the native electrocardiographic QRS duration after cardiac resynchronization therapy (CRT), might predict prognosis and improvement in echocardiographic outcomes. Methods and ResultsA total of 110 CRT recipients were retrospectively analyzed for the end points of death and hospitalization during 18 ± 3 months. Native QRS durations were recorded at baseline and 6 months after CRT (when pacing was switched off to obtain an electrocardiogram) to determine RER. CRT response and mitral regurgitation (MR) improvement were defined as ≥15% reduction in left ventricular end-systolic volume and absolute reduction in regurgitant volume (RegV) at 6 months, respectively. Overall, 48 patients (44%) had RER, which was associated with functional improvement (77% vs 34%; P < .001) and CRT response (81% vs 52%; P < .001) compared with those without RER. The change in the intrinsic QRS duration correlated with the reduction in RegV (r = 0.51; P < .001) and in tenting area (r = 0.34; P < .001). RER was a predictor of MR improvement (P = .023), survival (P = .043), and event-free survival (P = .028) according to multivariate analyses. ConclusionsNarrowing of the intrinsic QRS duration is associated with functional and echocardiographic CRT response, reduction in MR, and favorable prognosis after CRT.