Ventricular Pacing Site Research Articles

In silico pace mapping identifies pacing sites more accurately than inverse body surface potential mapping.

Electrocardiographic imaging (ECGi) is a noninvasive technique for ventricular tachycardia ablation planning. However, it is limited to reconstructing epicardial surface activation. In silico pace mapping combines a personalized computational model with clinical electrocardiograms (ECGs) to generate a virtual 3-dimensional pace map. The purpose of this study was to compare the ability of ECGi and in silico pace mapping to determine the site of ventricular pacing. ECGi recordings were collected during left ventricular (endocardial: n=5; epicardial: n=1), septal (n=3), and right ventricular (RV) apical (n=15) pacing along with computed tomography. Personalized computed tomography-based ventricular-torso computational models were created and aligned with the 252 ECGi vest electrodes. Ventricles were paced at 1000 random sites, and the corresponding body surface potentials (BSPs) and ECGs were derived. In silico pace maps were then reconstructed by correlating all simulated ECGs or BSPs with the corresponding paced clinical signals. The distance (d) between the pacing electrode (ground truth) and the location with the strongest correlation was determined; for ECGi, the site with the earliest activation time was used. In silico pace mapping consistently outperformed ECGi in locating the pacing origin, with the best results when all BSPs were used. During left ventricular pacing, the spatial accuracy of in silico pacing mapping was 9.5 mm with BSPs and 12.2 mm when using ECGs as compared with 30.8 mm when using ECGi. During RV pacing, d = 26.1 mm (BSPs), d = 30.9 mm (ECGs), and d = 29.1 mm (ECGi). In silico pace mapping is more accurate than ECGi in detecting paced activation. Performance was optimal when all BSPs were used and reduced during RV apical pacing.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

Pacemaker-induced atrial fibrillation reconsidered-associations with different pacing sites and prevention approaches.

The incidence of atrial fibrillation (AF) is significantly higher in patients with pacemakers than in the general population, which could be due to patient characteristics and the diagnostic tool of the pacemaker in detecting atrial high-rate episodes and subclinical AF, but also to the pacemaker itself providing AF-promoting conditions. It is well known that high ventricular pacemaker burden increases the likelihood of AF occurrence. However, the sites of atrial and ventricular pacing may also influence the risk for AF. The conventional sites for atrial and ventricular pacing are in the right atrial appendage and in the right ventricular apex. However, growing evidence suggests that alternative pacing sites may be superior for the prevention of AF. Bachmann bundle pacing, for example, promotes interatrial excitation conduction, resulting in atrial synchronicity and a shorter total atrial activation time, which may be preventive for the occurrence of AF. Moreover, in recent years, new ventricular pacing sites have come into focus with His bundle and left bundle branch pacing. In addition to the hemodynamic and electrophysiological cardiac benefits, these new options may also offer benefits in the prevention of AF. This review provides an overview of pacing-induced AF mechanisms and the association with different pacing sites, as well as approaches for prevention of pacing-induced AF, highlighting different sites and modes of atrial pacing and the newer sites of ventricular pacing.

Comparison between left bundle branch area pacing and right ventricular pacing: ventricular electromechanical synchrony and risk of atrial high-rate episodes.

The electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP. We consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up. The paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p < 0.001; LBBAP 113.56 ± 9.66 ms vs. RVS 148.23 ± 17.3 ms, p < 0.001. The LBBAP group showed shorter maximum difference (TDmax), and standard deviation (SD) of the time to peak systolic strain among the 18 left ventricular segments, and time of septal-to-posterior wall motion delay (SPWMD) compared with the RVA group (TDmax, 87.56 ± 56.01 ms vs. 189.85 ± 91.88 ms, p = 0.001; SD, 25.40 ± 14.61 ms vs. 67.13 ± 27.40 ms, p < 0.001; SPWMD, 28.75 ± 21.89 ms vs. 99.09 ± 46.56 ms, p < 0.001) and the RVS group (TDmax, 87.56 ± 56.01 ms vs. 156.46 ± 55.54 ms, p = 0.003; SD, 25.40 ± 14.61 ms vs. 49.02 ± 17.85 ms, p = 0.001; SPWMD, 28.75 ± 21.89 ms vs. 91.54 ± 26.67 ms, p < 0.001). The interventricular mechanical delay (IVMD) was shorter in the LBBAP group compared with the RVA group (-5.38 ± 9.31 ms vs. 44.82 ± 16.42 ms, p < 0.001) and the RVS group (-5.38 ± 9.31 ms vs. 25.31 ± 21.36 ms, p < 0.001). Comparing the RVA group and the RVS group, the paced QRS duration and IVMD were significantly shorter in the RVS group (QRS duration, 164.73 ± 14.49 ms vs. 148.23 ± 17.3 ms, p = 0.02; IVMD, 44.82 ± 16.42 ms vs. 25.31 ± 21.36 ms, p = 0.022). During follow-up, 2/16 (12.5%) LBBAP patients, 4/11 (36.4%) RVA patients, and 8/13 (61.5%) RVS patients had recorded novel AHREs. LBBAP was proven to be independently associated with decreased risk of AHREs than RVP (log-rank p = 0.043). LBBAP generates narrower paced QRS and better intro-left ventricular and biventricular contraction synchronization compared with traditional RVP. LBBAP was associated with a decreased risk of AHREs compared with RVP.

Lead performance of stylet-driven leads in left bundle branch area pacing: Results from a large single-center cohort and insights from in vitro bench testing

BackgroundLeft bundle branch area pacing (LBBAP) requires deep septal lead deployment for left-sided conduction stimulation. Advancing leads toward deep septal positions might add mechanical stress on these leads. Concerns about lead performance and reliability remain an unanswered question. ObjectiveThe purpose of this study was to analyze lead performance and integrity of stylet-driven pacing leads (SDLs) for LBBAP. MethodsThis study assessed lead fracture rates of SDL in a large single-center cohort of adult LBBAP patients. Fluoroscopic analysis of lead bending angulations at the septal insertion point and in vitro bench testing of lead preconditioning were performed to simulate clinical use conditions. Lead performance was compared between LBBAP and conventional right ventricular apical pacing (RVp) sites. ResultsThe study included 325 LBBAP patients (66% male; age 71±15 years). During median follow-up of 18 months, 2 patients (0.6%) experienced conductor fracture between tip housing and ring electrode, whereas no such fractures occurred with RVp patients (n = 149; P = .22). X-ray analysis revealed that high lead bending angulations occurred in 1.3% of the patients. Accelerated bench testing of excessive preconditioned leads showcased a higher probability of early conductor fracture compared to standard preconditioned leads. ConclusionThe incidence of early conductor failure in LBBAP seems higher than with conventional RVp sites. The most vulnerable lead part seems to be the interelectrode space between the tip housing and ring electrode. Excessive angulation and preconditioning might contribute to early fatigue fracture.

Activation time at left ventricular pacing site (QLV) in relation to actual site of latest activation; effect on response to cardiac resynchronization therapy

Abstract Background Among techniques to improve CRT efficacy, longer QLV (activation time at the left ventricular (LV) pacing site (LVPS)) has been proposed to correlate to response to cardiac resynchronization therapy (CRT), supporting that pacing close to the latest LV electrically activated site (LEAS) improves CRT efficacy. A QLV cut-off of &amp;gt; 95 ms has been proposed, however, predictive value was modest. This may be because LEAS was not identified, and empirically delivered leads may have missed it (described by a longer interval QLEAS (activation time at LEAS) to QLV. Purpose We compared QLEAS to QLV, and assessed effect of the interval QLEAS-QLV, on response to CRT. Methods We studied patients who had received CRT for Class I or Class IIa indications, regardless of CRT response, at 5 European sites. LV lead placement, device programming and follow up (FU) followed physician preference and site protocol. All patients had clinical FU 6-12 months post-implant, including echocardiographic study. CRT non-response was defined as LV end-systolic volume (LVESV) reduction of &amp;lt;15%. Patients underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. QLV and QLEAS were assessed from the noninvasive activation map in a blinded core lab. Logistic regression modelling was conducted for QLV and the interval QLEAS-QLV against CRT response, and the optimal cut-off points were calculated. Results Of 111 patients (age 64±11 years (mean±SD), 74% male, 98% LBBB, QRS duration 172±21 ms, baseline LVEF 28±6%, LVESV 183±87 mL, implant duration 12±5 months, 31%/69% NYHA Class II/III, 38% ischemic heart disease), 67% responded at 10±3 months post-implant. QLV overall was 97±23 ms (range 42-148 ms), 103±21 ms for responders and 83±22 for non- responders (p&amp;lt;0.001), QLEAS was 109±19 ms (range 66-150 ms), 109±20 ms for responders and 110±19 ms for non- responders (p=0.74). QLEAS-QLV overall was 13±18 ms (range 0-120 ms), 6±10 ms for responders and 27±22 ms for non-responders (p&amp;lt;0.001) (Figure 1). Optimal cut-off point for QLV was 85 ms with sensitivity 0.89, specificity 0.57 and an AUC of 0.742 (95% CI: 0.637- 0.846). Optimal cut-off point for QLEAS-QLV was 6 ms (sensitivity 0.77, specificity 0.95, AUC 0.901 (95% CI: 0.844-0.957) (Figure 1). The AUC of QLV cut-off and QLEAS-QLV cut-off differed significantly (p&amp;lt;0.001). 18/111 patients (16%) were non-responders despite a QLV≥85 ms, whereas 2 patients (2%) were non-responders despite a QLEAS-QLV≤6 ms. Conclusion QLEAS has greater discriminatory power than a QLV cut-off of 85 ms to separate CRT responders from non-responders in patients with LBBB and long QRS duration. QLV guided LV lead placement without prior knowledge of the latest LV activation in individual patients will miss the ideal LV pacing site in 16% of cases. Using noninvasive 3D global mapping to identify LEAS pre-CRT implant and directing LV lead placement to within 6 ms of this may improve CRT efficacy.Figure 1

CRT non-responder to responder conversion rate in the MORE-CRT MPP Trial.

To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after six months of standard biventricular pacing (BiVP). The trial enrolled 5,850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after six months of BiVP; non-response to BiVP was defined as < 15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional six months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (p=0.743). In patients with > 30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. Our trial shows that approximately 30% of patients, who do not respond to CRT in the first six months, experience significant reverse remodeling in the following six months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short/middle-term studies. MPP does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Combination of personalized computational modeling and machine learning for optimization of left ventricular pacing site in cardiac resynchronization therapy.

Introduction: The 30-50% non-response rate to cardiac resynchronization therapy (CRT) calls for improved patient selection and optimized pacing lead placement. The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPS between the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude. Materials and methods: We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC = 0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient. Results: The optimal ML-PS improved the ML-score by 17 ± 14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPS was shorter in the responders. The max ML-score and DPS were found to be strong predictors of CRT response (ROC AUC = 0.85). In the group with max ML-score > 0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16 ± 8% vs. 7 ± 8%). Conclusion: A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.

Localization of the ventricular pacing site from BSPM and standard 12-lead ECG: a comparison study

Inverse ECG imaging methods typically require 32–250 leads to create body surface potential maps (BSPM), limiting their routine clinical use. This study evaluated the accuracy of PaceView inverse ECG method to localize the left or right ventricular (LV and RV, respectively) pacing leads using either a 99-lead BSPM or the 12-lead ECG. A 99-lead BSPM was recorded in patients with cardiac resynchronization therapy (CRT) during sinus rhythm and sequential LV/RV pacing. The non-contrast CT was performed to localize precisely both ECG electrodes and CRT leads. From a BSPM, nine signals were selected to obtain the 12-lead ECG. Both BSPM and 12-lead ECG were used to localize the RV and LV lead, and the localization error was calculated. Consecutive patients with dilated cardiomyopathy, previously implanted with a CRT device, were enrolled (n = 19). The localization error for the RV/LV lead was 9.0 [IQR 4.8–13.6] / 7.7 [IQR 0.0–10.3] mm using the 12-lead ECG and 9.1 [IQR 5.4–15.7] / 9.8 [IQR 8.6–13.1] mm for the BSPM. Thus, the noninvasive lead localization using the 12-lead ECG was accurate enough and comparable to 99-lead BSPM, potentially increasing the capability of 12-lead ECG for the optimization of the LV/RV pacing sites during CRT implant or for the most favorable programming.

Variation in optimal hemodynamic atrio-ventricular delay of biventricular pacing with different endocardial left ventricular lead locations using precision hemodynamics.

It is not known whether the optimal atrioventricular (AVopt ) delay varies between left ventricular (LV) pacing site during endocardial biventricular pacing (BiVP) and may therefore needs consideration. We assessed the hemodynamic AVopt in patients with chronic heart failure undergoing endocardial LV lead implantation. AVopt was assessed during atrio-BiVPwith a "roving LV lead."Up to four locations were studied: mid-lateral wall, mid-septum (or a close alternative), site of greatest hemodynamic improvement, and LV lead implant site. The AVopt was compared to a fixed AV delay of 180 ms. Seventeen patients were included (12 male, aged 66.5 ± 12.8 years, ejection fraction 26 ± 7%, 16 left bundle branch block or high percentage of right ventricular pacing [RVP], QRS duration 167 ± 27 ms). In most locations (62/63), AVopt increased systolic blood pressure during BiVP compared with RVP (relative improvement 6 mmHg,interquartile range [IQR] 4-9 mmHg). Compared to a fixed AV delay, the hemodynamic improvement at AVopt was higher (1 mmHg, IQR 0.2-2.6 mmHg, p < .001). Within most patients (16/17), we observed a difference in AVopt between pacing sites (median paced AVopt 209 ms, IQR 117-250). Within this range, the hemodynamic impact of these differences was small (median loss 0.6 mmHg, IQR 0.1-2.6 mmHg). Within a patient, different endocardial LV lead locations have slightly different hemodynamic AVopt which are superior to a fixed AV delay. The hemodynamic consequence of applying an optimum from a different lead location is small.

Zero or near-zero x-ray pacemaker implantation in paediatric patients. dream or reality?

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Transvenous implantation of pacemaker is performed with fluoroscopy for leads’ insertion and implantation in the heart. This implies radiation exposure for patients and operators. Fluoroscopy allows a two-dimensional view of lead movements, and sometimes it is difficult to implant lead in the complex heart anatomy, or in alternative right ventricular (RV) pacing sites, that often requires higher radiation doses. These alternative pacing sites may prevent pacing-induced ventricular dysfunction. They are his bundle pacing area (HBP), ventricular septum close to the conduction system area (VS), RV outflow tract (RVOT). The use of three-dimensional-electroanatomic mapping system (3D-EAM) may reduce fluoroscopy and guide lead implantation. Published median fluoroscopy data for similar procedure are: 6 mGy (1), 13 mGy and 231 microGy/m2 (2). Purpose of this study is to seek out if a 3D-EAM-guided transvenous implantation into RV alternative sites pacing in paediatric patients can be accomplished with zero or near-zero X-rays. Methods Retrospective analysis of children and adolescents with congenital or acquired (idiopathic) complete atrioventricular block (CAVB) without other congenital heart defects who underwent 3D-EAM-guided pacing in alternative RV sites. The implant procedure was divided in 4 steps: 1-contrast venography; 2- 3D mapping: with a steerable catheter (femoral vein), the 3D-EAM acquired geometric reconstruction of the right heart and a pacing map identified RV sites with narrower paced QRS; 3-axillary vein puncture; 4-lead and pacemaker implantation: 3D-EAM guided stylet-directed screw-in lead implantation toward desired RV sites. Data are reported as median (25th-75th centiles). Results 54 CAVB patients (42 females), underwent 3D EAM-guided pacing (27 VVIR, 27 DDD) at age 11.5 (7.7-14) years, weight 42 (26-54) kg. Pacing sites were: 10 HBP, 4 RVOT, 40 VS (Figure 1). Procedure time was 170 (143-193) min, total fluoroscopy exposure and that of the 4 steps are reported in Table 1. The lowest exposures were: 0.2 mGy, 8 microGy/m2 (VVIR) and 0.6 mGy, 15 microGy/m2 (DDD). Paced QRS was 115 (100-120) ms. Conclusions 3D-EAM-guided alternative RV pacing sites was accomplished with very low fluoroscopic exposure, close to zero in some cases. Therefore, with 3D-EAM we can significantly reduce radiological doses also in difficult pacing procedures in paediatric patients, thus reducing radiological risks and preserving ventricular function. The dream is becoming reality.

Changes in myocardial perfusion according to left ventricular pacing site in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): 1. The Danish Heart Foundation 2. The Health Research Fund of the Central Denmark Region Background/Introduction Changes in left ventricular (LV) myocardial perfusion according to LV pacing site during cardiac resynchronization therapy (CRT) has only been sparsely described. Purpose To assess changes in LV global and regional myocardial perfusion according to LV pacing site after six months CRT. Methods Data from patients enrolled in the randomized controlled trial "Electrically vs. Imaging-guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy" was evaluated. Global and segmental absolute myocardial perfusion in ml/g/min was assessed by 82Rb-PET the day before CRT implantation and at six-months follow-up (6MFU). The exact LV pacing site was determined by post-implant cardiac CT. Perfusion and pacing site were evaluated using the standard 17’-segment LV model. Echocardiographic assessment of LV ejection fraction (EF) was performed the day before CRT implantation and at 6MFU. Results 93 patients (age 71±9 years; ischemic heart disease 48%; female 25%; median QRS 166±20 ms; mean LVEF 30±7%; NYHA class I/II/III/IV (%) 0/63/33/3) were included. Distribution of LV pacing sites is shown in Figure 1. No change in LV global perfusion was observed from baseline to 6MFU (0.79 to 0.81 ml/g/min, P=0.41; respectively). LV EF increased by 9±10%. Baseline global perfusion was higher in the 39 patients in whom LV EF had increased ≥10% at 6MFU (0.86 vs. 0.74 ml/g/min, P=0.02; respectively). However, no difference in perfusion-change was observed between patients with ≥10% increase in LV EF at 6MFU and patients with &amp;lt;10% increase (0.01 vs. 0.02 ml/g/min, P=0.76; respectively). Baseline perfusion was higher in the segments chosen for LV-pacing than in the non-paced segments (0.96 vs. 0.78 ml/g/min, P=0.00; respectively). Perfusion in the paced segments dropped to 0.86 ml/g/min (P=0.00) at 6MFU. Perfusion in the neighbouring segments also dropped during six months (from 0.91 to 0.86 ml/g/min, P=0.03), while perfusion in the non-paced and non-neighbouring segments increased (from 0.75 to 0.80 ml/g/min, P=0.01). Conclusion Despite a mean increase in LV EF of 9%, global myocardial perfusion remained unchanged. CRT resulted in a homogenous distribution of myocardial perfusion with a decreased perfusion in segments concordant and adjacent to LV pacing site and a corresponding increased perfusion in remote segments.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. NCT03280862.

Comparison of ventricular synchrony in children with left bundle branch area pacing and right ventricular septal pacing.

This study aimed to determine the ideal pacing site in children by comparing the postoperative ventricular synchrony in children with left bundle branch area pacing and those with right ventricular septal pacing. This retrospective study included children with complete atrioventricular block who underwent permanent pacemaker implantation from March 2019 to August 2021. Patients were grouped according to their ventricular pacing site, the left bundle branch area pacing group and the right ventricular septal pacing group. Two-dimensional speckle tracking echocardiography was used to evaluate the ventricular synchrony. Forty-eight children (median age, 2.7 years; interquartile range, 1.7-4.6 years) were included. The paced QRS duration in the left bundle branch area pacing group was significantly narrower than that in the right ventricular septal pacing group (100.2 ± 9.3 versus 115.4 ± 15.1 ms, p = 0.001). The median follow-up duration was 1.5 years (interquartile range, 1-2 years). At the last follow-up, the average capture threshold of the ventricular electrode in the left bundle branch area pacing group was lower than that in the right ventricular septal pacing group (0.79 ± 0.18 versus 1.20 ± 0.56 V, p = 0.008). The left ventricular intraventricular synchrony parameters in the left bundle branch area pacing group were better than those in the right ventricular septal pacing group (e.g. standard deviation of the time to peak longitudinal strain, 37.4 ± 4.3 versus 46.6 ± 8.2 ms, p = 0.000). The average interventricular mechanical delay time in the left bundle branch area pacing group was significantly shorter than that in the right ventricular septal pacing group (36.4 ± 14.2 versus 52.5 ± 22.7 ms, p = 0.016). Compared with right ventricular septal pacing, left bundle branch area pacing in children produces a narrower QRS duration and better pacing and ventricular synchrony parameters postoperatively.

621 TRANSVENOUS LEAD ADVANCEMENT IN PAEDIATRIC PACING TO OVERCOME GROWTH STRETCHING

Abstract Background One of the main complications of transvenous leads implanted in paediatric patients is the stretching of the lead caused by the somatic growth. It may cause pacing and sensing defects and lead dislodgement or even fracture. Absorbable lead ligature and atrial loop may reduce this risk. However, the loop may induce traction or may unroll too early and therefore impair lead function. Lead extraction and replacement is another solution, although it has some procedural risks in young patients. Lead advancement through pushing it from the pocket may solve growth-induced traction and spare the electrode throughout childhood until post-puberty. Objective of the study is the retrospective analysis of the outcome of the transvenous lead advancement in children with a pacemaker (PM) in a single tertiary paediatric center. Methods consecutive patients with a VVIR PM implanted for isolated congenital complete atrioventricular block (no structural heart disease) in alternative right ventricular (RV) pacing sites, with lead stretching underwent a trial of lead advancement during general anaesthesia, cefuroxime antibiotic profilaxis, from 2014 to 2021. After venous angiography showed venous patency, the PM pocket was opened, the lead was released from subcutaneous adherences and with a stylet was gently advanced to create a semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are expressed as median (25th-75th centiles). Results 8 patients underwent PM implantation at 6.8 (5.8-8.0) years of age, 20 (18-21) kg, 116 (106-120) cm, with the lead positioned at parahisian(3)/mid-septum (5 pts) sites. During a follow-up of 3 (1-5) years, advancement procedures were 1.5 (1.0-4.3) per patient. Between procedures, delta age was 16 (12-20) months, height 8 (7-11) cm and weight 5 (3-7) kg. All leads were successfully advanced without any procedural complications. Procedure time (skin to skin) was 96 (73-108) minutes, fluoroscopy was 0.5 (0.2-1.4) mGy, 16 (10-46) microGy/m2. Electrical lead parameters did not showed significant differences between consecutive control times. Conclusion the advancement of transvenous leads in children is a safe and effective procedure, with low fluoroscopy exposure, without significant acute and chronic complications. This procedure seems to preserve transvenous leads until growth has completed.

Risk of pacing-induced cardiomyopathy in patients with high-degree atrioventricular block – comparison between right ventricular pacing sites using computed tomography

Abstract Background Right ventricular (RV) pacing may induce significant left ventricular (LV) dyssynchrony resulting in pacing-induced cardiomyopathy (PICM). LV activation sequence is affected by RV pacing site and previous studies suggest that RV septal pacing may be superior compared to traditional RV apical pacing. However, results are conflicting and randomized controlled trials have failed to show clear benefits from RV septal pacing. Traditionally, studies have applied fluoroscopy to determine RV lead implantation site. However, locating pacing site using this method is known to be inaccurate and poorly reproducible compared with cardiac computed tomography (CT). The purpose of our study was to evaluate the association between RV pacing site determined by cardiac CT and risk of PICM. Methods We retrospectively included 153 patients with pre-implant LV ejection fraction (LVEF) ≥50% who underwent fluoroscopy-guided dual chamber pacemaker implantation due to high-degree atrioventricular block between March 2012 and May 2020. All patients attended a follow-up visit including cardiac CT and transthoracic echocardiography. RV lead position was evaluated from CT dividing the RV into three segments: apical, septum or free wall (Figure 1). Furthermore, RV lead position estimated by the implanting physician, using fluoroscopy during pacemaker implantation, was retrieved from medical records. The primary endpoint was PICM defined as ≥10% decrease in LVEF from time of pacemaker implantation to follow-up, resulting in LVEF &amp;lt;50%. Results Mean duration of follow-up was 3.7 years (range 2.1–8.7). The implanting physician estimated 131 (85.6%) leads to be located septal, 5 (3.3%) located non-septal and 17 (11.1%) were unknown. Based on CT, 48 (31.4%) leads were located septal and 105 (68.6%) were located non-septal of which 31 were located on the free wall (20.4%). With CT as the golden standard, 47 (35%) leads were estimated correctly during fluoroscopy-guided implantation. No significant differences between patient characteristics in the CT-estimated septal and non-septal groups were observed except for ischemic heart disease (P=0.05) (Table 1). There were 16 (33.3%) patients in the septal group who developed PICM compared to 31 (29.5%) in the non-septal group (P=0.6). Adjusting for ischemic heart disease did not change this result. In the septal group, the change in LVEF from baseline to follow-up was −9.0±10.4% compared to −7.5±9.1% in the non-septal group (P=0.4). Conclusion In total 31% developed PICM despite having a normal pre-implant LVEF with no observed difference between RV septal and non-septal pacing. With CT as the golden standard, RV leads were inaccurately located during fluoroscopy-guided pacemaker implantation with only 35% being located correctly. Misclassification of pacing sites in previous studies may have contributed to the inconsistent results. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Svend Andersens FondKarl G Andersens Fond

Predictors of right ventricular pacing-induced left ventricular dysfunction in pacemaker recipients with preserved ejection fraction

Pacing is an effective treatment in the management of patients with bradyarrhythmias. Chronic right ventricular pacing may cause electrical and mechanical dyssynchrony leading to adeterioration of left ventricular ejection fraction (LVEF). This deterioration of LVEF has been described as pacing-induced cardiomyopathy (PICM). The incidence of PICM has been described by many studies, ranging between 10% and 26%. Predictors for PICM are not yet established-studies were limited by variations in the definition of PICM and the follow-up period. The authors studied the incidence and predictors of PICM in patients with preserved LVEF who underwent pacemaker implantation. This retrospective study included 320patients that underwent single- or dual-chamber pacemaker implantation, with amean follow up period of 4.7 ± 2.0years. Implantable cardioverter defibrillator and cardiac resynchronization therapy patients were excluded from this study. Individuals that had abaseline LVEF ≥ 50% before implantation in transthoracic echocardiography were included in the study. Of the 320patients included in the study, 45% were male, with amean age 55.5years. The incidence of PICM was 7.5%. Wider native QRS duration, particularly > 140 ms (P < 0.001), wider paced QRS (pQRS) duration > 150 ms (P < 0.001), low normal ejection fraction < 56% pre-implantation (P = 0.023) and increased LV end diastolic diameter (LVEDD) > 53 mm and LV end systolic diameter (LVESD) > 38 mm (P < 0.001) predicted the development of PICM. There was no association between burden of right ventricular pacing (P = 0.782) or pacing site (P = 0.876) and the development of pacemaker-induced cardiomyopathy. Right ventricular pacing-induced left ventricular dysfunction is not uncommon, with an incidence of 7.5%. Wider native and paced QRS durations, low normal ejection fraction (< 56%) pre-implantation and increased LVEDD and LVESD post implantation are the most important predictors for the development of PICM.

Status and Update on Cardiac Resynchronization Therapy Trials.

After decades of clinical use, cardiac resynchronization therapy (CRT) can be considered an established therapy. However, there are multiple open questions to be addressed that shall further improve the proportion of patients responding to CRT. Progress in better understanding the relationship between electrical and mechanical disorder in patients with heart failure with ventricular conduction abnormalities is important. This article presents and discusses ongoing studies in different areas of CRT research, including patient selection by novel diagnostic tools, extension of clinical criteria, left ventricular lead positioning and pacing site selection, optimization of CRT delivery and programming, and selection of device type.

Transvenous lead advancement in paediatric pacing to overcome growth stretching

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction One of the main complications of transvenous leads implanted in paediatric patients is the stretching of the lead caused by the somatic growth. It may cause pacing and sensing defects and lead dislodgement or even fracture. Absorbable lead ligature and atrial loop may reduce this risk. However, the loop may induce traction or may unroll too early and therefore impair lead function. Lead extraction and replacement is another solution, although it has some procedural risks in young patients. Lead advancement through pushing it from the pocket may solve growth-induced traction and spare the electrode throughout childhood until post-puberty. Purpose of the study is the retrospective analysis of the outcome of the transvenous lead advancement in children with a pacemaker (PM) in a single tertiary paediatric center. Methods Consecutive patients with a VVIR PM implanted for isolated congenital complete atrioventricular block (no structural heart disease) in alternative right ventricular (RV) pacing sites, with lead stretching underwent a trial of lead advancement during general anaesthesia, cefuroxime antibiotic profilaxis, from 2014 to 2021. After venous angiography showed venous patency, the PM pocket was opened, the lead was released from subcutaneous adherences and with a stylet was gently advanced to create a semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are expressed as median (25th-75th centiles) Results: 7 patients underwent PM implantation at 6.9 (5.5-8.0) years of age, 20 (18-21) kg, 116 (106-120) cm, with the lead positioned at parahisian(3)/mid-septum (4 pts) sites. During a follow-up of 3 (1-5) years, advancement procedures were 2 (1-4) per patient. Between procedures, delta age was 15 (12-19) months, height 7 (6-11) cm and weight 4 (2-6) kg. All leads were successfully advanced without any procedural complications. Procedure time (skin to skin) was 91 (69-105) minutes, fluoroscopy was 0.4 (0.2-1.2) mGy, 13 (9-35) microGy/m2. Electrical lead parameters did not showed significant differences between consecutive control times. In one parahisian pacing, chronic threshold increased after 3 years (2 advancement procedures) from 0.7V to 2.6 V/0.4 ms. Conclusion the advancement of transvenous leads in children is a safe and effective procedure, without significant procedural complications and during follow-up, and with low fluoroscopy exposure. This procedure may maintain a good function of transvenous leads until growth has completed.

Impact of right ventricular pacing site on the subcutaneous ICD sensing-a step towards personalised device therapy?

Patients with an existing subcutaneous implantable cardiac defibrillator (S-ICD) may develop a pacing indication. When transvenous pacing is not feasible, combining an S-ICD and a leadless pacemaker (LP) can be a reasonable option. There are reports of concomitant use of both devices. However, the effect of pacing on the S-ICD sensing is not well studied. We hypothesise that pacing changes R and T-wave amplitudes, causing changes in R:T ratios as perceived by a S-ICD, increasing the risk for T wave oversensing (TWO) during paced rhythm with a subsequent risk of inappropriate shocks. This is a prospective study in patients undergoing electrophysiological studies. Participants were fitted with a Holter®, and the leads were placed to correspond to the vectors of an S-ICD. The right ventricle was paced at four positions for 10 beats each at 8mA/2ms. The Holter® traces were analysed, using two-way analysis of variance (ANOVA) to assess the effect of pacing on the R:T ratio. Forty-seven patients (age 56.02 ± 16.02, 72% male) were enrolled (81% structurally normal heart, 15% dilated cardiomyopathy, 2% ischaemic cardiomyopathy, and 2% adult congenital heart disease). Age, sex, and aetiology had no effect on the R:T ratio. Pacing caused significant changes in the R:T ratio. There was no significant difference in the R:T ratios between the pacing sites (p < 0.001). Pacing alters the R:T ratio significantly in most patients, theoretically increasing the risk for TWO and inappropriate shocks. Tailored programming for both devices is important for concomitant use of LPs and S-ICDs.