Atrioventricular Delay Research Articles

Acute Electrical Synchronization Achieved with Dynamic Atrioventricular Delays during Biventricular and Left Ventricular MultiPoint Pacing

BackgroundCardiac resynchronization therapy (CRT) response relies on two factors: when and where to pace. These factors may be enhanced by dynamic atrioventricular delays (AVDs) (e.g., SyncAV CRT, Abbott) and multi-site left ventricular (LV) pacing (e.g., MultiPoint Pacing [MPP], Abbott). Their individual and combined synchronization contributions have not been evaluated across a comprehensive spectrum of pacing configurations. The objective is to distinguish the acute electrical synchrony achieved by (i) static vs. dynamic AVDs, (ii) single- vs. multi-site LV pacing, and (iii) with vs. without RV pacing. MethodsCRT-indicated patients with LBBB and intact AV conduction (PR<250ms) were enrolled and evaluated during implant. Acute changes in 12-lead ECG QRS duration (QRSd) were evaluated during: intrinsic conduction, biventricular pacing (BiV), biventricular MPP, LV-only single-site pacing (LVSS), and LV-only MPP (LVMPP). CRT modes were evaluated with static AVDs and optimized SyncAV AVDs. ResultsCRT implant and QRSd evaluation were completed in 85 patients (71% male, 34% ischemic, 179ms PR). The median intrinsic QRSd of 165ms was reduced by BiV, MPP, LVSS, and LVMPP without SyncAV to 144ms (by 14%), 142ms (16%), 155ms (8%), and 149ms (12%), respectively (P<0.01 vs. intrinsic). BiV+SyncAV, MPP+SyncAV, LVSS+SyncAV, and LVMPP+SyncAV reduced the intrinsic QRSd significantly further to 128ms (by 23%), 124ms (26%), 131ms (21%), and 129ms (24%) (P<0.0001, each corresponding pair). ConclusionsMPP combined with SyncAV achieved the narrowest QRSd, in the overall population and in the most patients, by delivering ventricular pacing from all available sites (RV+LV1+LV2) while timed with dynamic AVDs.

Introducing a Novel Pacemaker‐Mediated Arrhythmia: The Pseudo‐RNRVAS Arising From Atrial Capture Challenges

ABSTRACTBackgroundThis study aimed to define and explain a novel form of pacemaker‐mediated arrhythmia which is initiated and sustained by atrial capture loss coinciding with ventriculoatrial (VA) conduction within the postventricular atrial refractory period (PVARP). Unlike repetitive nonreentrant VA synchrony (RNRVAS), in the pseudo‐RNRVAS, the atrium is not stimulated due to pacing below the threshold level, rather than because of refractory atrial myocardium.ObjectiveThe objective was to elucidate the mechanisms of this pseudo‐RNRVAS, identify predisposing factors, and propose preventive strategies.MethodsTwenty‐one patients with dual‐chamber cardiac implantable electronic devices (CIEDs) exhibiting stable VA conduction within the PVARP were included. Pseudo‐RNRVAS were induced by altering atrial amplitude and lower rate interval while keeping other CIED parameters constant.ResultsPseudo‐RNRVAS developed after atrial capture loss in 20 out of 21 patients. Notably, 11 patients experienced pseudo‐RNRVAS at heart rates ≤ 70 bpm, and 7 patients at AV delay ≤ 150 ms. The condition initiated immediately following the first ventricular pace beat after atrial capture loss in 18 patients. In six cases, pseudo‐RNRVAS terminated intermittently and then restarted; in 14 cases, it did not resolve.ConclusionPseudo‐RNRVAS can occur even at low heart rates and without specific predisposing factors seen in RNRVAS. Conditions that increase atrial pacing probability and threshold raise the likelihood of pseudo‐RNRVAS. Early postimplantation may pose a heightened risk, correlating with pacemaker syndrome and susceptibility to heart failure.

Larger QRS but better hemodynamic function after high output His bundle pacing in patients with heart failure and narrow QRS. A paradox or a new concept?

Abstract Background QRS duration is an important factor in determining Cardiac Resynchronisation Therapy (CRT) response and a useful surrogate for electromechanical dyssynchrony. However, we don’t have studies confirming this concept in conduction system pacing. Purpose We performed His Bundle Pacing (HBP) with high output (3.5V/1msec) in HF patients with dilated or ischemic cardiomyopathy and narrow QRS to evaluate hemodynamic benefit independent of the QRS duration or AV delay shortening. Methods 14 patients with dilated (7 patients) or ischemic (7 patients) cardiomyopathy (EF&amp;lt;35%) and narrow QRS (&amp;lt;120ms) were referred for implantation of a defibrillator. We implanted an ICD- HBP system, and we collected clinical, echocardiographic, and electrocardiographic data. Results We obtained HBP in all 14 patients successfully. PQ after implantation was shorter from 172±48 to 143±16 (P=0.048) so as to pace the ventricle. Baseline QRS duration increased after pacing from 110±15 to 123±16ms (P=0.008) as measured by ECG analyzer. Despite this increase in QRS duration basal mean EF increased from 30±4% to 46±10% (P&amp;lt;0.001) after a median follow-up of 17 months. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume decreased from 62±5 to 57±5mm (P=0.013) and from 195±69 to 126±27ml (P&amp;lt;0.001), respectively. Left ventricular end-systolic volume decreased from 139±58 to 69±27 (P&amp;lt;0.001). TAPSE increased from 19±4 to 27±4. NYHA class decreased by one class in every patient after only one month. HBP threshold was 1.05V±0.7/1msec and raised to 1.33±0.93/1msec (due mainly to 2 patients with very high threshold). The impedance was 588±109 and decreased to 484±69 Ohms. R-wave at implant was 3.2±1.8mV. In 2 out of 14 patients, threshold increased but was still less than 3.5V/1msec. Conclusions HBP in HF patients with dilated or ischemic cardiomyopathy and narrow QRS improves hemodynamic function in right and left ventricle and decreases NYHA class. This benefit appears to be produced by a higher stimulation output despite a larger QRS after pacing. We exclude that a very short AV delay could be favorable, by measuring acute EF changes only after increasing the pacing output without AV delay modifications. To our knowledge these are the first cases of beneficial HBP in HF patients with narrow QRS. Interestingly, larger QRS corresponds to higher EF in patients with high output HIs Bundle Pacing.

Implementing dynamic atrioventricular delay optimization for cardiac resynchronization therapy: an economic analysis in the EU5 countries

Abstract Background Heart failure (HF) poses an escalating public health challenge, contributing significantly to patient morbidity, mortality and healthcare expenditures [1,2]. Cardiac resynchronization therapy (CRT) is a well-established intervention that improves functional capacity and enhances quality of life while mitigating symptoms, hospitalizations, and mortality in HF patients [3]. Nevertheless, the reaction to CRT varies among individuals; some experience positive responses and others show resistance to the therapy, with unfavourable outcomes and increased healthcare costs [4]. The introduction of the dynamic atrioventricular (AV) optimization algorithm aims to enhance CRT response by enabling dynamic optimization of the AV delay [4]. Purpose Despite the strong clinical evidence supporting the effectiveness of dynamic AV optimization algorithm, a comprehensive assessment of its economic implications is still lacking. This study aims to evaluate the economic impact of activating dynamic AV optimization algorithm in patients undergoing CRT treatment across the Big 5 European countries (EU5; France, Germany, Spain, Italy, and the UK). Methods The study examines two scenarios over a 3-year timeframe: a) current scenario, where dynamic AV optimization algorithm activation is limited to a small segment of the population, and b) future scenario, where dynamic AV optimization algorithm activation is progressively expanded per year from 15% to 50%. Treatment efficacy data, measured in terms of HF hospitalization and mortality rates, were sourced from Varma et al. studies [1,4]. Hospitalization and mortality costs were extracted from national DRG tariffs and relevant literature [5–14]. It is important to note that there is no additional cost for algorithm activation if the device is already equipped with it. Results In this hypothetical analysis of 1,000 patients, around 30% undergo CRT implantation compatible with dynamic AV optimization algorithm activation. The treatment cost of patients with the algorithm ON is reduced by -15% compared to patients with the algorithm OFF, considering a weighted average across the EU5 countries (France: -11%, Germany: -16%, Italy: -14%, Spain -17%, UK: -16%), as shown in Table 1. The steady increase in algorithm activation led to an annual expenditure reduction equal to €21,109, calculated on the weighted average across the EU5 countries (France: €15,549, Germany: €33,753, Italy: €13,844, Spain: €20,385, UK: £13,423). When compared to the current scenario, the future scenario saved €36,468 on average across the EU5 countries. Further country-specific cost savings are shown in Table 2. Conclusion The conducted economic analysis gives confidence in dynamic AV optimization algorithm, positioning it as a valuable and economically sustainable asset for enhancing CRT treatment outcomes in patients with HF.

Comparative study of the effects of preferential left ventricular and biventricular pacing on echocardiographic and cardiorespiratory indices and clinical status of heart failure patients: preliminary

Abstract Introduction Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLV-P) can achieve left ventricle resynchronization allowing for intrinsic activation of the right side, and benefit cardiac output while reducing atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute. Methods We evaluated the effects of a pLVP algorithm on 100 systolic heart failure patients ( all Caucasians, 49% male; 67 +/- 8 years old; 51% ischemic cardiomyopathy; 44% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response. Results Significant comparative effects of pLV-P over optimized CRT were noted regarding right ventricle systolic velocity in TDI at 12-months from baseline (mean (SE); 4.5(0.8), p=0.035); decrease in end-diastolic volume of left ventricle (mean (SE); 11.33(7), p=0.035); decrease in right ventricle strain mean ((SE); 9.2(2.1), p=0.03). According to other echocardiographic indices, again taking into account baseline levels, patients in pLV-P group exhibited lower E/e value at 6-months (mean (SE); 8.390(4,3), p=0.04), and at 12 -months (mean (SE); 7.45(3.9), p=0.035); improved values in left atrium contractility strain at 12-months (mean (SE); 8.390(0.8), p=0.04); a borderline improvement in left ventricular ejection fraction (mean (SE); 8.7(433), p=0.05) at 12-months; and borderline improvement in left ventricular longitudinal strain at 6-months (mean (SE); 4.9(2.6), p=0.035), compared to optimized CRT. In CPET, taking into account baseline levels, patients in the pLVP group showed higher METs at 12-months (mean (SE); 1,16(0.8), p=0.03) compared to opt CRT group; higher predicted Ventilation rate (%) even from 6-months (mean (SE); 8.167(5,7), p=0.03) and higher predicted peak VO2 (%) at 6 months (mean (SE); 34,13(14), p=0.03) and borderline significance at 12 months (mean (SE); 4.88(3), p=0.08), compared to opt CRT. Conclusions In the preliminary findings of READAPT study, it seems that pLVP optimized by a standardized echocardiographic protocol in patients with preserved AV conduction and LBBB, can achieve improvement in parameters of right ventricular and left atrium structure and function, as well as in survival-predictive parameters of CPET compared to optimized CRT during the 12-months of follow-up.

The implementation of speckle tracking echocardiography for cardiac resynchronization therapy optimization. A rotational myocardial mechanics interpretation

Abstract Background Cardiac resynchronization therapy (CRT) has an additive therapeutic influence on left ventricular (LV) function in heart failure (HF) patients, but the underlying mechanisms through which it works are not completely explained. Our aim was to further elucidate the role of this intervention via rotational mechanics using 2D speckle tracking echocardiography (2D-STE). Methods We investigated 46 patients (65 ± 9 years) who received CRT. All enrolled patients were assessed on admission by 2D-STE and 6 min walk test (6m WT) and followed in the outpatient device clinic by 2D-STE (at one week and 6 months post-implantation) and 6m WT (at 6 months post-implantation). On their first appointment all biventricular systems were optimized by atrioventricular delay optimization and by changing the temporal activation of ventricular electrodes aiming to reach the highest effective LV stroke volume (eff SV) across all activation options. A new 2D-STE based index (twist integral – TI) targeting to assess the rotational mechanics of the whole cardiac cycle was also measured to further explain the CRT response. For the calculation of LV TI of the full cardiac cycle, serial isochronal apical and basal rotation measurements (in degrees) were exported to a worksheet Excel file and the final algebraic summation was calculated by the formula: Twist Integral = (systolic twist integral – diastolic twist integral) Σ twisti= twist1+twist2+...+twistn (table 1). Results Twenty-two (48%) patients with dilated cardiomyopathy as the predominant aetiology of HF were responders at 6-month follow-up. The commonest selected mode that was related with the greatest LV performance response was the simultaneous activation of the 2 ventricular leads (39%). The strongest predictor of CRT response was the improvement of eff SV between admission and first appointment at clinic, followed by the improvement of TI, the non-existence of CAD, and the improvement of peak systolic twist (table 2). Conclusions Additional CRT optimization via changing the temporal activation of ventricular electrodes is beneficial for LV performance in HF patients. Rotational mechanics essentially explain the beneficial CRT contribution to these patients.

Comparison of acute hemodynamic effect of prioritizing ventricular resynchronization vs left ventricular filling during optimization of cardiac resynchronization therapy

BackgroundTargeting maximal ventricular resynchronization, with the shortest QRS duration (QRSd), is commonly implemented after cardiac resynchronization therapy (CRT). ObjectiveThe purpose of this study was to compare optimization of ventricular resynchronization with optimization of left ventricular (LV) filling during CRT by measuring their acute hemodynamic effects. MethodsPatients with standard CRT indications, recruited from 2 centers, underwent biventricular pacing (BVP) and left bundle branch pacing (LBBP). We performed a within-patient comparison of acute hemodynamic response of systolic blood pressure (SBP) at the atrioventricular delay (AVD) with the shortest QRSd against the AVD with the most efficient LV filling. In a validation substudy, we also performed electrical assessment using QRS area (QRSa) and hemodynamic assessment with the maximum rate of LV pressure rise (dP/dtmax). ResultsThirty patients (age 65 ± 10 years; 53% male) were recruited. The AVD producing maximal ventricular resynchronization was associated with a significantly shorter QRSd (difference 15 ± 12 ms for BVP and 18 ± 13 ms for LBBP, both P <.01) and a significantly smaller improvement in SBP (difference −3 ± 4 mm Hg for BVP and −2 ± 2 mm Hg for LBBP, both P <.01) compared with the AVD that optimized filling. Similar findings were observed in the substudy, with a significantly smaller improvement in dP/dtmax assessed with QRSd and QRSa (difference −9% ± 7% and −6% ± 4% during BVP, and −5% ± 6% and −3% ± 3% during LBBP, all P <.01). ConclusionTargeting the maximal ventricular resynchronization results in suboptimal acute hemodynamic performance with both BVP and LBBP as CRT. These findings support prioritizing LV filling when programming AVD for CRT.

New-Onset Left Ventricular Dysfunction After Left Bundle Branch Pacing.

Left bundle branch pacing (LBBP) provides stable pacing parameters and has been suggested as an alternative for right ventricular pacing and cardiac resynchronization therapy. The aim of the study was to assess the incidence and etiology of new-onset left ventricular dysfunction (NOLVD) following LBBP in patients with baseline normal left ventricular (LV) function and cardiomyopathy patients with normalized LV function. Patients undergoing successful LBBP for symptomatic bradyarrhythmia or as an alternative to cardiac resynchronization therapy were included. Normalization of LV function was defined as improvement in LV ejection fraction to≥50%. Patients with baseline normal LV function and those with recovered LV function after LBBP constituted the study group. Loss of conduction system capture (LOCSC) was defined as complete or partial loss of right bundle branch delay pattern along with inability to demonstrate capture transition during threshold assessment. A total of 426 patients were included; 59% (n=250) had baseline normal LV function (group I) and 41% (n=176) had recovered LV function after LBBP (group II). Mean follow-up duration of 28.3 ± 16.7months. NOLVD was noted in 3.75% (n=16; group I=5 and group II=11) of patients. The etiologies for NOLVD were LOCSC in 62.5% (n=10), suboptimal atrioventricular (AV) delay in 18.7% (n=3), atrial fibrillation in 6.3% (n=1), and idiopathic in 12.5% (n=2). LOCSC occurred at a mean interval of 9.2 ± 6.4months after the initial implantation. Reinterventions (n=6) including lead repositioning, AV delay optimization, and AV junction ablation resulted in renormalization of LV function in all 6 patients. Periodic assessment in device clinic is required because NOLVD from reversible causes can occur duringfollow-up in patients after LBBP.

Editorial comments to “Increased interleukin‐6 levels are associated with atrioventricular conduction delay in severe COVID‐19 patients”

Editorial comments to “Increased interleukin‐6 levels are associated with atrioventricular conduction delay in severe <scp>COVID</scp>‐19 patients”

Increased interleukin-6 levels are associated with atrioventricular conduction delay in severe COVID-19 patients.

Severely ill patients with coronavirus disease 2019 (COVID-19) show an increased risk of new-onset atrioventricular blocks (AVBs), associated with high rates of short-term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)-6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL-6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID-19. We investigated (1) the behavior of PR-interval and PR-segment in patients with severe COVID-19 during active phase and recovery, and (2) their association with circulating IL-6 levels over time. During active disease, COVID-19 patients showed a significant increase of PR-interval and PR-segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR-indices significantly correlated with circulating IL-6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR-prolonging drugs, repurposed or not. Our study provides evidence that in patients with severe COVID-19 and high-grade systemic inflammation, IL-6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short-term mortality. Our data provide further support to current anti-inflammatory strategies for severe COVID-19, including IL-6 antagonists.

Predictors of the efficacy of His bundle pacing in patients with a prolonged PR interval: A stratified analysis of the HOPE-HF randomized controlled trial.

The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VO2max) but there was significant improvement in heart failure specific quality of life. In this pre-specified secondary analysis, we evaluated the impact of baseline PR interval, echocardiographic E-A fusion, and the magnitude of acute high-precision haemodynamic response to pacing, on outcomes. All 167 randomized participants underwent measurement of PR interval, acute haemodynamic response at optimized AV delay, and assessment of presence of E-A fusion. We tested the impact of these baseline parameters using a Bayesian ordinal model on VO2max, quality of life and activity measures. There was strong evidence of a beneficial interaction between the baseline acute haemodynamic response and the blinded benefit of pacing for VO2 (Pr 99.9%), Minnesota Living With Heart Failure (MLWHF) (Pr 99.8%), MLWHF physical limitation score (Pr 98.9%), EQ-5D visual analogue scale (Pr 99.6%), and exercise time (Pr 99.4%). The baseline PR interval and the presence of baseline E-A fusion did not have this reliable ability to predict the clinical benefit of pacing over placebo across multiple endpoints. In the HOPE-HF trial, the acute haemodynamic response to pacing reliably identified patients who obtained clinical benefit. Patients with a long PR interval (≥200 ms) and left ventricular impairment who obtained acute haemodynamic improvement with AV-optimized His bundle pacing were likely to obtain clinical benefit, consistent across multiple endpoints. Importantly, this gradation can be reliably tested for before randomization, but does require high-precision AV-optimized haemodynamic assessment to be performed.

Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Endless loop tachycardia among patients with devices having advanced preventive algorithms: A case series and brief review.

Endless loop tachycardia (ELT) is the commonest pacemaker mediated tachycardia (PMT) encountered among patients with cardiac implantable electronic devices (CIEDs). Despite being enabled with various preventive algorithms, we encountered several cases having recurrent, long, and symptomatic ELT. We retrospectively analyzed consecutive device checkups at device clinic at a single center of eastern India between January 2019 to March 2023. There were 20 cases of confirmed and sustained ELT among 4520 device checks. Although mostly benign, in two cases ELT led to clinical worsening in patients having left ventricular (LV) systolic dysfunction. Even with good ventricular function, ELT resulted in improper atrioventricular (AV) synchrony leading to disabling symptom in one case. The differentiation of ELT from sinus tachycardia and atrial tachycardia (AT) was not always easy. Magnet application is certainly useful to differentiate. The situations that provoked ELT in this study were-long AV delays, VIP (ventricular intrinsic preferences)/MVP (managed ventricular pacing), atrial non-capture, atrial under/over sensing, premature ventricular contractions (PVCs)/couplets, premature atrial contractions (PAC) and slower ventriculo-atrial (VA) conduction. Rate responsive shortening of post-ventricular atrial refractory period (PVARP) also promoted its occurrence and hindered troubleshooting. When ELT occurred despite post-PVC extension of PVARP, lowering the atrial sensitivity, switching to bipolar sensing and manual setting of longer PVARP after measuring VA conduction time were useful. "Rate responsive PVARP" had to be turned off in a few cases to prevent ELT. On the contrary, an over aggressive prolongation of PVARP led to repetitive non-reentrant ventriculo-atrial synchrony (RNRVAS) in two cases. Checking VA conduction during implantation and noninvasive program stimulation (NIPS) during follow up were useful to check the tendency for ELT. Clinically significant ELT is rare but not uncommon among devices having in-built preventive algorithms. Manual adjustments are often useful to troubleshoot the same.

Optimizing electrical efficacy of leadless cardiac resynchronization therapy and leadless left ventricular septal pacing: Insights on left and right ventricular activation from electrocardiographic imaging

BackgroundLeadless cardiac resynchronization therapy (CRT) using the WiSE-CRT system is an emerging heart failure treatment. An implanted electrode delivers lateral or septal endocardial left ventricular pacing (LVP) upon detection of a right ventricular pacing (RVP) stimulus from a co-implanted device, thus generating biventricular pacing (BiVP). Electrical efficacy data regarding this therapy, particularly leadless LV septal pacing (LVSP) for potential conduction system capture, is limited. ObjectiveTo evaluate the acute performance of leadless CRT using electrocardiographic imaging (ECGi), and assess the optimal pacing modality (OPM) of LVSP based on RV and LV activation. MethodsTen WiSE-CRT recipients underwent an ECGi study testing: RVP; BiVP; LVP only; and LVP with an optimised atrioventricular delay (LV-OPT). BiV, LV and RV activation times (BIVAT-90, LVAT-95, RVAT-90), plus LV and BiV dyssynchrony index (LVDI, BIVDI) were calculated from reconstructed epicardial electrograms. The individual OPM yielding the greatest improvement from baseline was determined. ResultsBiVP generated a 23.7% improvement in BiVAT-90 (p=0.002). An improvement of 43.3% was observed at OPM (p=0.0001), primarily through reductions in RVAT-90. At OPM, BiVAT-90 improved in patients with lateral (43.3%, p=0.0001, n=5) and septal LV implants (42.4%, p=0.009, n=5). The OPM varied by individual. LVP or LV(OPT) were mostly superior in patients with LVSP, and for those in SR and LBBB (n=4). ConclusionLeadless CRT significantly improves acute ECGi-derived activation and dyssynchrony metrics. Using an individualised OPM improves efficacy in selected patients. Effective LVSP is feasible, with fusion pacing at LV(OPT) mitigating the potential deleterious effects on RV activation.

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.

Outcomes with physiologic His bundle pacing in patients with narrow QRS complex

BackgroundIn patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. ObjectiveThis study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. MethodsIn 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. ResultsThe paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. ConclusionIn patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

Impact of myocardial phenotype on atrioventricular delay optimization at rest and during exercise: insights from a virtual patient study

Abstract Background The usefulness of atrioventricular delay (AVD) optimization in cardiac resynchronization therapy (CRT) for heart failure (HF) patients with left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF) is still debated. Yet, studies have not explored the role of non-electrical myocardial disease substrates in determining optimal AVD settings among patients. Purpose We first hypothesized that acute response to AVD optimization might be modulated by various myocardial disease substrates. Furthermore, we hypothesized that cardiac function is more sensitive to changes in AV coupling during exercise and that this sensitivity is also modulated by underlying myocardial disease substrates. Methods We used the CircAdapt model of the human heart and circulation to simulate different types of LV remodeling that can be found in CRT candidates. First, an LBBB-like pattern of mechanical activation was imposed by delaying LV free wall (LVFW) and interventricular septal (IVS) activation relative to right ventricular free wall activation. Then, two types of LV remodeling were simulated by LV dilation with preserved or impaired myocardial contractility, resulting in LVEF &amp;lt;35%. To investigate the effect of diastolic dysfunction, we increased passive myocardial stiffness of the IVS and LVFW on both substrates with LV remodeling until a mean left atrial pressure (mLAP) of 14 mmHg was reached. CRT was simulated by resynchronizing IVS and LVFW. AVD optimization was conducted by gradually reducing the paced AVD from 220 ms to 40 ms in steps of 20 ms. In each simulation, the optimal paced AVD at rest (cardiac output (CO) and heart rate (HR) of 4.2 L/min and 80 bpm, respectively) was assessed using stroke volume (SV) and mLAP which is used as a measure of LV filling pressure. To investigate the relative effect of these myocardial phenotypes during AVD optimization under exercise, CO and HR were increased step-wise. Results The gain in SV by AVD optimization was larger in the simulations with healthy myocardium than in those with hypo-contractile and stiff myocardium (Figure 1: top-row). However, mLAP was comparably decreased by AVD optimization in healthy and diseased myocardium (Figure 1: bottom row). During exercise, the optimum AVD shifted to shorter values (Figure 2: top-row), and mLAP was much more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium (Figure 2: bottom row). Conclusion Virtual patient simulations show that both myocardial hypocontractility and stiffness dampen the effect of AVD optimization on SV. Furthermore, simulations suggest that patients benefit more from AVD optimization during exercise than during resting conditions. These mechanistic insights may help to gain more benefit from AVD optimization for patients undergoing CRT.AVD optimization at restAVD optimization during exercise

Effectiveness of dynamic atrioventricular optimization during patient exercise in cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is considered the standard treatment for patients with heart failure and prolonged QRS duration. Recent studies suggest that atrioventricular delay (AVD) optimization can play a key role in QRS narrowing, thus improving CRT outcomes. For this purpose, device-based algorithms have been developed. In particular, the SyncAV algorithm continuously monitors the patient’s intrinsic AVD and dynamically adjusts the pacing AVD to allow fusion of the left ventricle pacing with intrinsic right ventricle depolarization. SyncAV optimization is usually performed in a single patient condition, i.e. at rest, and in a single operating scenario of the device, i.e. during atrial sensing. Purpose This study aims to compare QRS narrowing after AVD optimization using SyncAV in CRT-treated patients at rest, during moderate exertion, and during an increase in the atrial pacing rate. Methods This is a prospective, non-randomized, non-blinded, multicenter study. The study population consisted of patients in sinus rhythm, PR interval &amp;lt; 350 ms, and rest ventricular rate &amp;lt; 100 bpm. Within one month from the implant, patients were assessed for AVD optimization with SyncAV, selecting the offset (i.e. 10 to 40% AVD) that resulted in the shortest QRS duration (QRSd). Subsequently, patients performed moderate physical activity using a bicycle ergo-meter while a surface ECG was collected. QRSd was assessed once patients achieved a heart rate over 20 bpm to baseline heart rate, up to 100 bpm. Finally, QRSd narrowing was evaluated during a programmed increase in atrial pacing (i.e. &amp;gt;20 bpm of baseline atrial rate). Results Nine patients were treated with CRT and enrolled (age 67,3 ± 13,2 years; 66% male; LV ejection fraction 33,7±2,9 %; intrinsic QRSd 155,6 ± 12,7 ms) with intact atrioventricular conduction (PR interval 170,6±25,8 ms). The median SyncAV offset that provided the best QRSd reduction was 20 % (10 - 35%). Intrinsic QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 122,0 ± 11,2 ms (-21,2±8,5%) with SyncAV optimization. During exercise the mean heart rate was 88,1 bpm, the QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 124,9 ± 14,9 ms (-19,3±10,8 %) with SyncAV optimization. The mean heart rate during atrial pacing was 90 bpm with paced QRSd of 126,0 ±13,9 ms (-18,9±7,3% from baseline) with SyncAV optimization and paced PR interval of 198,2±22,7ms. Conclusion We evaluated the effectiveness of SyncAV for AVD optimization in out-of-clinic. This study demonstrates the possibility of narrowing the QRSd using SyncAV at several activity levels. Nevertheless, a deeper evaluation is needed to confirm our findings, investigating the SyncAV role in a larger population of patients.

Electrocardiographic predictors of haemodynamic benefit from biventricular pacing: the role of atrioventricular timing measures

Abstract Background Patients with heart failure (HF) and left bundle branch block (LBBB) are selected for biventricular pacing (BVP) cardiac resynchronisation therapy (CRT) based on their 12-lead ECG QRS complex duration (QRSd). This is due to the long-held belief that BVP delivers its beneficial effects almost exclusively by reducing ventricular dyssynchrony. Recent work (1) suggests that atrioventricular delay (AVD) shortening is another key mechanism of benefit and, therefore, that atrioventricular timing may be an important CRT substrate. The ideal 12-lead ECG measure to facilitate patient selection that yields benefits from this mechanism is yet to be elucidated. Purpose We set out to establish whether incorporating a measure of AV delay provides additional benefit over and above using QRSd when using the 12-lead ECG to select patients who are likely to obtain haemodynamic benefit from BVP. Methods We identified patients in sinus rhythm with HF and LBBB meeting clinical criteria for CRT who had undergone implantation of a BVP device and had also undergone high-precision haemodynamic assessment of BVP. This is where pacing is alternated between atrium-only pacing (AAI) and DDD pacing using BVP multiple times for each of a full range of AVDs during continuous beat-by-beat blood pressure recording to determine the peak haemodynamic benefit of BVP in each patient. We extracted potentially predictive, pre-specified intrinsic (unpaced) ECG features that incorporated left or right AV timing to varying extents: PR interval (PR), end-of-p-wave-to-R-wave-peak-time-V6 (Pend-RWPTV6), start-of-p-wave-to-end-of-QRS (P-QRSend) as well as conventional QRSd. Pearson's test assessed the unadjusted correlation between intrinsic ECG intervals and BVP haemodynamic benefit(∆SBP). A multiparametric regression analysis model was constructed to account for confounders and interactions between different ECG features. Results 53 eligible patients were identified. 39 were male (73.6%), 31 had non-ischaemic aetiology (58.5%), mean LVEF was 27.6% ± SD 4.79 and mean LVEDD was 57.9± SD 9.4mm. Unadjusted correlations between intrinsic ECG features were not strong but favoured P-QRSend as a potentially predictive feature; R2 values: PR 0.28 (p=0.04), Pend-RWPTV6 0.19 (p=0.18), P-QRSend 0.27 (p=0.054), QRSd 0.045 (p=0.75). However, the multiparametric model revealed that utilising both PR interval and Pend-RWPTV6 in a predictive model showed better-adjusted correlation with BVP haemodynamic benefit (R2 0.54, p=0.04). Conclusion ECG features that incorporate either right (PR interval) or left (Pend-RWPTV6) AVD or both (P-QRSend) are superior to QRSd for predicting haemodynamic benefit from BVP in patients with HF and LBBB. This further reinforces the role of AVD shortening as a mechanism of benefit of BVP and suggests that selecting patients on the basis of AV timing may yield more overall benefit from CRT delivered by BVP or potentially conduction system pacing.ECG interval measurementCorrelation Graphs

The effect of bachmann bundle pacing on diastolic function in patients with non-obstructive HCM

Abstract Background and Objective Patients with non-obstructive HCM (nHCM) have advanced diastolic dysfunction and atrial remodeling, leading to increased heart failure hospitalisations. The objective of this study was to evaluate the role of Bachmann bundle pacing (BBP) in diastolic filling compared to right atrial appendage pacing (RAAP). Methods Forty patients with symptomatic nHCM and normal LV function were prospectively enrolled from January 2021 to June 2023. Inclusion criteria included electrocardiographic evidence of inter-atrial delay, E/e’ &amp;gt; 15, and an indication for ICD implantation. BBP was attempted in twenty patients, others underwent RAAP. A Biotronik Selectra 3D 40-S sheath was used for BBP in patients in whom initial lead implantation was unsuccessful. BBP was defined based on P-wave morphology and fluoroscopic lead position. The RV lead was implanted in the RV apex in all patients and the AV delay was optimized based on diastolic filling period and E/e’. Devices were programmed in DDD mode. During follow up, diastolic function, functional capacity, atrial fibrillation, and heart failure hospitalisations were assessed in both groups. Results Among the forty patients (age 48.2+7.8 yrs, males 75%, ESC-SCD Risk 4.3+0.6%), the baseline P wave duration, E/A, E/e’ were 138.4+16.4 ms, 2.5+0.5, and 17.5+2.4, respectively. Six patients (15%) had a history of paroxysmal AF (3 each in BBP and RAAP groups). Of the 16 patients (80%) who underwent successful BBP, the Selectra 3D 40-S sheath was used in 8 patients (Figure 1, Panel A). During BBP, a bachmann bundle potential was recorded in 7 of 16 patients (43.8%) (Figure 1, Panel C). The pacing threshold (1.5+0.5@0.4ms vs. 0.9+0.3@0.4ms, p=0.026) was higher and the atrial sensing (1.8+0.4 vs. 3.3+0.6, p=0.002) was lower in the BBP group compared to the RAAP group at 4 weeks and 6 months of follow up. There was an acute rise in threshold (2.1@0.4 ms) in 1 BBP patient at 4 weeks of follow up. Patients in the BBP group had a reduction in P wave duration compared to the patients in the RAAP group (-22.5 + 5.4 vs. +5.6 + 3.2 ms, p&amp;lt;0.001). During follow up (11.4 + 3.4 months), there was a significant improvement in diastolic function (E/e’), functional capacity (NYHA Class) and reduction in NT-proBNP in the BBB group compared to the RAAP group (Figure 1). The percentage of atrial pacing was similar in both groups (BBP 73.2 + 7.8 vs. RAAP 78.5 + 9.1 %, p=0.219). The risk of atrial fibrillation/tachycardia (12.5% vs. 35.0%, p=0.022) and heart failure hospitalisations (6.3% vs. 20%, p=0.042) was lower in the BBP group compared with RAAP during follow up. Conclusions BBP is safe and effective in improving diastolic function, functional capacity and heart failure hospitalizations in patients with nHCM.BBP Pacing using Selectra 3D 40-S SheathChange in E/e', NYHA, and NT-pro BNP