Antonius Martinus Wilhelmus van Stipdonk

QRS area reflects ventricular electrical dyssynchrony and is a stronger predictor of cardiac resynchronization therapy (CRT) outcome than QRS duration/morphology. Data on QRS area in patients upgraded from right ventricular pacing to CRT are scarce. We investigated whether QRS area and the difference with biventricular paced QRS area (ΔQRS) in CRT-upgraded patients are associated with clinical outcome and echocardiographic response. This retrospective multicenter study included patients upgraded to CRT. Median values were used as a cut-off for (Δ)QRS area. The primary composite outcome was all-cause mortality, heart transplantation or left ventricular assist device. Secondary outcomes were heart failure hospitalization (HFH) and ≥15% reduction in left ventricular end-systolic volume. A total of 303 patients were included (age 69 ± 11 years, 75% male, 50% ischemic cardiomyopathy). Median LVEF was 26% [25–34]; baseline QRS area was 132 µVs [97–162], which reduced to 90 µVs [61–122] with CRT (p < 0.001), with a ∆QRS area of 35 µVs [1–74]. The primary outcome occurred in 34.3% during 47 ± 29 months of follow-up without differences between a small or large baseline and ∆QRS area (p = 0.856; p = 0.968). HFH occurred in 9.2% and patients with large ∆QRS area had fewer HFHs (6.7% versus 15.4%, p = 0.012). Baseline QRS area of >132 µVs was not associated with HFH (p = 0.832), but was a determinant of better echocardiographic response (OR 2.23, 95% CI 1.10–4.50, p = 0.026). ∆QRS area of >35 µVs was not associated with echocardiographic response (p = 0.203). To conclude, (∆)QRS area was not associated with the primary outcome in this small cohort of CRT-upgraded patients. However, baseline QRS area of >132 µVs was associated with echocardiographic response and ∆QRS area of >35 µVs with fewer HFHs.

The left atrioventricular coupling index (LACI), defined as the ratio of left atrial (LA) to left ventricular (LV) end-diastolic volumes, serves as a surrogate for atrioventricular coupling. Cardiac resynchronization therapy (CRT) promotes reverse remodeling of both chambers and may enhance atrioventricular coupling, yet the clinical utility of LACI in CRT patients remains unclear. This study evaluated the effect of CRT on LACI and assessed its prognostic value for CRT response. In 123 patients enrolled in the ADVISE-CRT III trial (mean age 66 ± 10 years; 63% male; and 81% with a Class I CRT indication), LACI was measured by echocardiography before and six months after CRT implantation. Multivariable linear and logistic regression analyses were performed to assess the association between LACI and CRT response (≥ 15% LV end-systolic volume reduction), adjusting for potential confounders. Low baseline LACI was independently associated with an 11.2% greater LV end-systolic volume reduction (Quartile 1–2 vs. Quartile 3–4; p = 0.009) and 3.6-fold higher odds of CRT response (p = 0.041). At six months, LACI increased significantly in responders (16.5% to 20.7%; p < 0.001), driven by greater LV versus LA end-diastolic volume reduction. In non-responders, LACI remained stable (20.9% to 20.3%; p = 0.077). LACI was independently associated with CRT response and provided incremental value over individual LA and LV volumetric parameters. While LACI may reflect favorable structural substrate and atrioventricular coupling at baseline, it is not suitable for post-CRT assessment of atrioventricular coupling, as disproportionate LV versus LA remodeling may conceal coupling improvements. Graphical abstract Left atrioventricular coupling index in patients undergoing cardiac resynchronization therapy

Background and Aims: CRT improves outcomes in heart failure patients with electrical dyssynchrony. The QLV interval, a marker of delayed left ventricular (LV) activation, independently predicts CRT response. This study aimed to determine whether activation time measured in surface ECG lead V8 reflects postero-lateral LV delay by correlating with the QLV interval during biventricular (BiV) CRT implantation. Methods: Consecutive patients with wide QRS (non-RBBB) undergoing BiV-CRT or generator change were prospectively enrolled. Surface ECGs were recorded with the V5 electrode repositioned to the V8 location. Local wavefront activation was determined using the steepest negative downslope of the precordial leads, referred to as the negative derivative activation time (NDAT). The LV lead was connected to the EP recording system, and NDAT and QLV measurements were obtained. Results: Forty-three patients were included. The NDAT in V8 strongly correlated with the QLV interval (r = 0.895; mean difference 1 ± 11 ms) across both LBBB and IVCD patterns. In contrast, NDAT in V6 showed weaker correlation (r = 0.592; mean difference 21 ± 24 ms). During LV-only pacing, a QS morphology in V8 consistently indicated postero-lateral lead placement. More anterior/apical lead positions showed larger QLV–NDAT V8 differences and non-QS morphologies, indicating suboptimal positioning. Conclusion: NDAT in lead V8 is a non-invasive marker of delayed activation in the postero-lateral LV, outperforming V6 in identifying late activation. When combined with LV-paced QRS morphology, V8 facilitates accurate lead localization without additional tools. These findings may support the use of lead V8 to refine patient selection and optimize CRT delivery.

Vectorcardiography (VCG) is an electrophysiological investigation technique, giving supplementary information about the electrical activation of the heart, compared to traditional 12-lead electrocardiography (ECG). Whereas the 12-lead ECG has found its way into global clinical cardiology practice in numerous cardiac pathophysiological instances, VCG has not. In an investigation of the electrical activation of the heart in cardiac resynchronization therapy (CRT), in order to understand the baseline pathology in potentially eligible patients, and to understand and optimize CRT-derived paced activation of the heart in the therapy’s recipients, all of these aspects are essential to the success of the therapy. Due to a consistently present group of non-responders in CRT, VCG has gained interest as a potential improvement in this field. This review comprehensively summarizes the contemporary evidence for the additional value of VCG in CRT, as well as current deficiencies in evidence, to support its implementation in global practice in addition to, or as a substitution for, traditional 12-lead ECG.

Aims: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have become established in preventing sudden cardiac death, with some advantages over transvenous defibrillator systems, including a lower incidence of lead failures. Despite technological advancements, S-ICD carriers may suffer from significant complications, such as premature battery depletion (PBD), that led to an advisory for nearly 40 000 patients. This multicentre study evaluated the incidence of PBD in a large set of S-ICD patients. Methods and results: Data from patients implanted with S-ICD models A209 and A219 between October 2012 and July 2023 across nine centres in Europe and the USA were reviewed. Incidence and implications of PBD, defined as clinically observed sudden drop in battery longevity, were analysed and compared to PBD with the definition of battery depletion within 60 months. Prospectively collected clinical data were obtained retrospectively from medical records, device telemetry, and manufacturer reports. This registry is listed on ClinicalTrials.gov (NCT05713708). Of the 1112 S-ICD devices analysed, 547 (49.2%) were equipped with a potentially affected capacitor linked to PBD occurrence, currently under Food and Drug Administration advisory. The median follow-up time for all patients was 46 [inter-quartile range (IQR) 24–63] months. Clinically suspected PBD was observed in 159 (29.1%) of cases, with a median time to generator removal or replacement of 65 (IQR 55–72) months, indicative of significant deviations from expected battery lifespan. Manufacturer confirmation of PBD was made in 91.7% of devices returned for analysis. No cases of PBD were observed in devices that were not under advisory. Conclusion: This manufacturer-independent analysis highlights a notable incidence of PBD in patients equipped with S-ICD models under advisory, and the rate of PBD in this study corresponds to the rate currently estimated by the manufacturer. To the best of our knowledge, this provides the largest contemporary peer-reviewed study cohort investigating the actual incidence of PBD in S-ICD patients. These findings emphasize the importance of post-market registries in collaboration between clinicians and the manufacturer to optimize safety and efficacy in S-ICD treatment.

Aims: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) offer potentially distinct advantages over transvenous defibrillator systems. Recent randomized trials showed significantly lower lead failure rates than transvenous ICD. Still, S-ICDs remain associated with the risk of inappropriate shocks (IAS). While previous studies have reported varying causes of IAS, this study explores a rare cause of IAS, referred to as ‘sense-B-noise.’ It was recently described in case series, but its incidence has not been studied in a large cohort of S-ICD patients. Methods and results: We retrospectively reviewed data from patients implanted with S-ICD models 1010, A209, and A219 between October 2009 and July 2023 across nine centres in Europe and the USA. The analysis concentrated on determining the incidence and understanding the implications of sense-B-noise events. Sense-B-noise represents a rare manifestation of distinct electrogram abnormalities within the primary and alternate sensing vectors. Data were collected from medical records, device telemetry, and manufacturer reports for investigation. This registry is registered on clinicaltrials.gov (NCT05713708). Subcutaneous implantable cardioverter-defibrillator devices of the 1158 patients were analysed. The median follow-up time for all patients was 46 (IQR 23–64) months. In 107 patients (9.2%) ≥1 IAS was observed during follow-up. Sense-B-noise failure was diagnosed in six (0.5 and 5.6% of all IAS) patients, in all patients, the diagnosis was made after an IAS episode. Median lead dwell time in the affected patients was 23 (2–70) months. To resolve the sense-B-noise defect, in three patients reprogramming to the secondary vector was undertaken, and two patients underwent system removal with subsequent S-ICD reimplantation due to low amplitude in the secondary vector. In one patient, the secondary vector was initially programmed, and subsequently, an S-ICD system exchange was performed due to T-wave-oversensing IAS episodes. Conclusion: This multicentre analysis’ findings shed light on a rare but clinically highly significant adverse event in S-ICD therapy. To our knowledge, we provide the first systematic multicentre analysis investigating the incidence of sense-B-noise. Due to being difficult to diagnose and limited options for resolution, management of sense-B-noise is challenging. Complete system exchange may be the only option for some patients. Educating healthcare providers involved in S-ICD patient care is crucial for ensuring accurate diagnosis and effective management of sense-B-noise issues.

Background: Cardiac Resynchronization Therapy (CRT) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of conventional biventricular pacing (BiVP), 6-16% of patients develop ventricular tachyarrhythmias (VTAs) within a year of implantation. The relationship between BiVP and the development of VTAs is still under debate. During BiVP, the left-sided epicardium-to-endocardium activation creates a non-physiological activation and hence a non-physiological repolarization, which might trigger VTAs. A novel alternative treatment option to BiVP that on the contrary induces a left ventricular endocardium-to-epicardium activation, is left bundle branch area pacing (LBBAP). We hypothesized that LBBAP leads to a more homogenous repolarization than conventional BiVP. Purpose: To compare time-dependent activation and repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods: Patients eligible for CRT who underwent LBBAP (n=21) or BiVP (n=94) were retrospectively included. Standard 12-lead electrocardiograms obtained prior to implantation [baseline], shortly following implantation (0-2 days, [acute phase]), and after prolonged pacing during follow-up (31-180 days, [chronic phase]) were analyzed. QRS duration and QRS area were calculated through reconstruction of the vectorcardiogram and further analyzed together with corrected QT (QTc) and corrected Tpeak-Tend (Tp-e,c) intervals using a semi-automatic approach in MATLAB. Differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed-rank tests. Significance was defined as a p-value ≤0.05. Results: (see figure): Compared to baseline, QRS duration and QRS area decreased significantly during the acute phase (both p < 0.01) and stabilized during chronic pacing for both BiVP and LBBAP patients. Differences in QRS duration or QRS area between LBBAP and BiVP were not significant at any of the time points. In the acute phase, BiVP resulted in a temporary and significant prolongation of both QTc and Tp-e,c compared to baseline (both p < 0.01). However, there was a subsequent shortening observed between the acute and chronic phases for both QTc and Tp-e,c (both p < 0.01). Compared to baseline, LBBAP acutely shortened Tp-e,c (p = 0.02) and tended to shorten QTc. During chronic pacing, LBBAP shortened QTc and Tp-e,c compared to baseline (p = 0.01 and p < 0.01). The decreases in QTc and Tp-e,c were larger in LBBAP than in BiVP patients in the acute and chronic pacing phase (all p <0.01). Conclusion: CRT induces activation changes in both BiVP and LBBAP patients to a comparable extent. While BiVP leads to an acute increase in repolarization dispersions, LBBAP reduces markers of repolarization dispersion compared to baseline. The diminished dispersion of repolarization might contribute to an antiarrhythmic effect with LBBAP.

Background: The QRS area shows promise as a vectorcardiographic (VCG) marker for electrical dyssynchrony in patient selection for cardiac resynchronization therapy (CRT). Nevertheless, little information is known about the underlying cardiac electrical substrate it may reflect. Purpose: The aim of this study was to compare the VCG QRS area with measures of cardiac electrical dyssynchrony derived from electrocardiographic imaging (ECG-imaging). Methods: QRS area from the synthesized VCG (Kors transformation matrix from the 12-lead ECG) was computed for 27 patients who underwent ECG-imaging (11 patients with no history of structural heart disease and 16 consecutive CRT patients). ECG-imaging measures for electrical dyssynchrony analyzed were: ventricular electrical uncoupling (VEU) computed as the difference between the average LV and RV activation times from ECG-imaging, standard deviation of activation times from the left ventricle (LV SDAT, and the maximal activation (Max AT). Pearson correlation analyses between VCG QRS area and ECG-imaging measures of dyssynchrony were carried out for the entire cohort and for patients with a wide-QRS only. Results: ECG-imaging measures of dyssynchrony compared with QRS area in 11 patients with no structural heart disease with narrow-QRS (blue) and 16 candidates for CRT with heart failure (HF) and predominantly wide-QRS (LBBB [n=6], IVCD [n=8], RVpaced [n=1], and nQRS-HF [n=1]) are provided in Figure 1. QRS area were associated with all ECG-imaging measures of dyssynchrony. However, sub-analysis in only the wide-QRS patients revealed that QRS area exhibited the strongest association with VEU. Conclusion: Vectorcardiographic QRS area is associated with cardiac electrical dyssynchrony on ECG-imaging, exhibiting a particularly strong association with ventricular electrical uncoupling.