Comparing Ventricular Synchrony in Left Bundle Branch and Left Ventricular Septal Pacing in Pacemaker Patients

Background: Left bundle branch area pacing (LBBAP) has recently been introduced as a novel physiological pacing strategy. Within LBBAP, distinction is made between left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP, no left bundle capture). Objective: To investigate acute electrophysiological effects of LBBP and LVSP as compared to intrinsic ventricular conduction. Methods: Fifty patients with normal cardiac function and pacemaker indication for bradycardia underwent LBBAP. Electrocardiography (ECG) characteristics were evaluated during pacing at various depths within the septum: starting at the right ventricular (RV) side of the septum: the last position with QS morphology, the first position with r' morphology, LVSP and-in patients where left bundle branch (LBB) capture was achieved-LBBP. From the ECG's QRS duration and QRS morphology in lead V1, the stimulus- left ventricular activation time left ventricular activation time (LVAT) interval were measured. After conversion of the ECG into vectorcardiogram (VCG) (Kors conversion matrix), QRS area and QRS vector in transverse plane (Azimuth) were determined. Results: QRS area significantly decreased from 82 +/- 29 mu Vs during RV septal pacing (RVSP) to 46 +/- 12 mu Vs during LVSP. In the subgroup where LBB capture was achieved (n = 31), QRS area significantly decreased from 46 +/- 17 mu Vs during LVSP to 38 +/- 15 mu Vs during LBBP, while LVAT was not significantly different between LVSP and LBBP. In patients with normal ventricular activation and narrow QRS, QRS area during LBBP was not significantly different from that during intrinsic activation (37 +/- 16 vs. 35 +/- 19 mu Vs, respectively). The Azimuth significantly changed from RVSP (-46 +/- 33 degrees) to LVSP (19 +/- 16 degrees) and LBBP (-22 +/- 14 degrees). The Azimuth during both LVSP and LBBP were not significantly different from normal ventricular activation. QRS area and LVAT correlated moderately (Spearman's R = 0.58). Conclusions: ECG and VCG indices demonstrate that both LVSP and LBBP improve ventricular dyssynchrony considerably as compared to RVSP, to values close to normal ventricular activation. LBBP seems to result in a small, but significant, improvement in ventricular synchrony as compared to LVSP

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response

Introduction Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction ( increment QRS area) after CRT with the outcome. We hypothesize that a larger increment QRS area is associated with a better survival and echocardiographic response. Methods and Results Electrocardiograms (ECG) obtained before and 2-12 months after CRT from 1299 patients in a multi-center CRT-registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12-lead ECGs. The primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end-systolic volume reduction >= of 15%. Patients with increment QRS area above the optimal cut-off value (62 mu Vs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33-0.56, p = 109 mu Vs, survival, and echocardiographic response were better when the increment QRS area was >= 62 mu Vs (p = 109 mu Vs, increment QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967-0.994, p = .006). Conclusion increment QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome

Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-specific Response to Cardiac Resynchronization Therapy

Background - Women are less likely to receive cardiac resynchronization therapy (CRT), yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better CRT response in women. For this the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared to conventional electrocardiographic markers. Methods - Data from a multicenter registry of 725 CRT patients (median follow-up: 4.2 years [IQR: 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area, and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV-ratio on the association between sex and LV reverse remodeling (end-systolic volume change: ΔLVESV) and sex and the composite outcome of all-cause mortality, LV assist device implantation or heart transplantation was assessed. Results - At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area: 132±55μVs vs 123±58μVs, p=0.043) which was, even more pronounced for the QRSarea/LVEDV-ratio (0.76±0.46μVs/ml vs 0.57±0.34μVs/ml, p<0.001). After multivariable analyses female sex was associated with ΔLVESV (β 0.12, p=0.003) and a lower occurrence the composite outcome (HR 0.59 (0.42-0.85), p=0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV-ratio in women (25-fold change in Beta from 0.12 to 0.09). The larger QRSarea/LVEDV-ratio did not contribute to the better survival observed in women. In both volumetric responders and non-responders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted HR 0.59 (0.36-0.97), p=0.036 and 0.55 (0.33-0.90), p=0.018, respectively). Conclusions - Greater electrical dyssynchrony in smaller hearts contributes in part to more reverse remodeling observed in women after CRT, but this does not explain their better long-term outcomes

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint—echocardiographic reduction of left ventricular end-systolic volume (LVESV)—were evaluated. Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT

Association of vectorcardiographic T-wave area with clinical and echocardiographic outcomes in cardiac resynchronization therapy

Aims: Data on repolarization parameters in cardiac resynchronization therapy (CRT) are scarce. We investigated the association of baseline T-wave area, with both clinical and echocardiographic outcomes of CRT in a large, multi-centre cohort of CRT recipients. Also, we evaluated the association between the baseline T-wave area and QRS area. Methods and results: In this retrospective study, 1355 consecutive CRT recipients were evaluated. Pre-implantation T-wave and QRS area were calculated from vectorcardiograms. Echocardiographic response was defined as a reduction of ≥15% in left ventricular end-systolic volume between 3 and 12 months after implantation. The clinical outcome was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Left ventricular end-systolic volume reduction was largest in patients with QRS area ≥ 109 μVs and T-wave area ≥ 66 μVs compared with QRS area ≥ 109 μVs and T-wave area < 66 μVs (P = 0.004), QRS area < 109 μVs and T-wave area ≥ 66 μVs (P < 0.001) and QRS area < 109 μVs and T-wave area < 66 μVs (P < 0.001). Event-free survival rate was higher in the subgroup of patients with QRS area ≥ 109 μVs and T-wave area ≥ 66 μVs (n = 616, P < 0.001) and QRS area ≥ 109 μVs and T-wave area < 66 μVs (n = 100, P < 0.001) than the other subgroups. In the multivariate analysis, T-wave area remained associated with echocardiographic response (P = 0.008), but not with the clinical outcome (P = 0.143), when QRS area was included in the model. Conclusion: Baseline T-wave area has a significant association with both clinical and echocardiographic outcomes after CRT. The association of T-wave area with echocardiographic response is independent from QRS area; the association with clinical outcome, however, is not

Comparison of the relation of the ESC 2021 and ESC 2013 definitions of left bundle branch block with clinical and echocardiographic outcome in cardiac resynchronization therapy

INTRODUCTION: We aimed to investigate the impact of the 2021 European Society of Cardiology (ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes. METHODS: The MUG (Maastricht, Utrecht, Groningen) registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%). RESULTS: The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan-Meier curves of HTx/LVAD/mortality (p < .0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non-LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition. CONCLUSION: The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination

Background: Integration of a patient’s non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019–10–07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013–11–12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient (ICC) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error (χ2) of LV myocardial strain, strain rate, and cavity volume. Results: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients (χ2 < 1.6), but minimum parameter reproducibility was poor (ICCmin = 0.01). Iterative reduction yielded a reproducible (ICCmin = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs (χ2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). Conclusions: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient’s underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making

Incidence of premature battery depletion in subcutaneous cardioverter-defibrillator patients: insights from a multicenter registry.

BACKGROUND The subcutaneous ICD established its role in the prevention of sudden cardiac death in recent years. The occurrence of premature battery depletion in a large subset of potentially affected devices has been a cause of concern. The incidence of premature battery depletion has not been studied systematically beyond manufacturer-reported data. METHODS Retrospective data and the most recent follow-up data on S-ICD devices from fourteen centers in Europe, the US, and Canada was studied. The incidence of generator removal or failure was reported to investigate the incidence of premature S-ICD battery depletion, defined as battery failure within 60 months or less. RESULTS Data from 1054 devices was analyzed. Premature battery depletion occurred in 3.5% of potentially affected devices over an observation period of 49 months. CONCLUSIONS The incidence of premature battery depletion of S-ICD potentially affected by a battery advisory was around 3.5% after 4 years in this study. Premature depletion occurred exclusively in devices under advisory. This is in line with the most recently published reports from the manufacturer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04767516

ECG patterns in cardiac resynchronization therapy

Cardiac resynchronization therapy is an established treatment modality in heart failure. Though non-response is a serious issue. To address this issue, a good understanding of the electrical activation during underlying intrinsic ventricular activation, biventricular as well as right- and left ventricular pacing is needed. By interpreting the 12-lead electrocardiogram, possible reasons for suboptimal treatment can be identified and addressed. This article reviews the literature on QRS morphology in cardiac resynchronization therapy and its role in optimization of therapy