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Aims: The field of conduction system pacing (CSP) is evolving, and our aim was to obtain a contemporary picture of European CSP practice., Methods and Results: A survey was devised by a European CSP Expert Group and sent electronically to cardiologists utilizing CSP. A total of 284 physicians were invited to contribute of which 171 physicians (60.2%; 85% electrophysiologists) responded. Most (77%) had experience with both His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Pacing indications ranked highest for CSP were atrioventricular block (irrespective of left ventricular ejection fraction) and when coronary sinus lead implantation failed. For patients with left bundle branch block (LBBB) and heart failure (HF), conventional biventricular pacing remained first-line treatment. For most indications, operators preferred LBBAP over HBP as a first-line approach. When HBP was attempted as an initial approach, reasons reported for transitioning to utilizing LBBAP were: (i) high threshold (reported as >2 V at 1 ms), (ii) failure to reverse bundle branch block, or (iii) > 30 min attempting to implant at His-bundle sites. Backup right ventricular lead use for HBP was low (median 20%) and predominated in pace-and-ablate scenarios. Twelve-lead electrocardiogram assessment was deemed highly important during follow-up. This, coupled with limitations from current capture management algorithms, limits remote monitoring for CSP patients., Conclusions: This survey provides a snapshot of CSP implementation in Europe. Currently, CSP is predominantly used for bradycardia indications. For HF patients with LBBB, most operators reserve CSP for biventricular implant failures. Left bundle branch area pacing ostensibly has practical advantages over HBP and is therefore preferred by many operators. Practical limitations remain, and large randomized clinical trial data are currently lacking., Competing Interests: Conflict of interest: Medtronic supported the survey project; however, the views and opinions expressed are those of the authors and not Medtronic and therefore no relevant conflicts of interest to report., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Conduction system pacing (CSP) is an emerging and promising approach for physiological ventricular pacing. While data from randomized controlled trials are scarce, use of His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP) has increased in France., Aim: To perform a national snapshot survey for cardiac electrophysiologists to evaluate adoption of CSP in France., Methods: An online survey, distributed to every senior cardiac electrophysiologist in France, was conducted in November 2022., Results: A total of 120 electrophysiologists completed the survey. Eighty-three (69%) respondents reported experience in undertaking CSP procedures and 27 (23%) were planning to start performing CSP in the coming 2 years. The implantation techniques and criteria used for successful implantation differed significantly among operators. The most frequent indications for HBP and LBBAP were high-degree atrioventricular block with left ventricular ejection fraction (LVEF) < 40% (24 and 82%, respectively) or with LVEF ≥ 40% (27 and 74%, respectively), and after failure of a coronary sinus left ventricular lead (27 and 71%, respectively). The limitations respondents most frequently perceived when performing HBP were bad sensing/pacing parameters (45%), increased procedure duration (41%) and risk of lead dislodgement (30%). The most frequently perceived limitations to performing LBBAP were absence of guidelines or consensus (31%), lack of medical training (23%) and increased procedure duration (23%)., Conclusions: Our national survey-based study supports wide adoption of CSP in France. CSP is currently used as a second-line approach for both antibradycardia and resynchronization indications, with important variations regarding implantation techniques and criteria for measuring success., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Frequency and distribution of left ventricular (LV) venous collaterals were studied in vivo to evaluate the ease and feasibility of implanting a new ultra-thin LV quadripolar microlead for cardiac resynchronization therapy (CRT)., Methods and results: Evaluable venograms were analyzed to define the prevalence of venous collaterals (>0.5 mm diameter) between: (1) different LV segments; and (2) different major LV veins in: unselected patients who underwent CRT from 2008 to 2012 at Rouen Hospital, France (retrospective); and CRT patients from the Axone Acute pilot study in 2018 (prospective). In prospective patients with evaluable venograms, LV microlead implantation was attempted. Thirty-six (21/65 retrospective, 15/20 prospective) patients had evaluable venograms with ≥1 visible venous collaterals. Collaterals were found between LV veins in all CRT patients with evaluable venograms. Regionally, prevalence was highest between: the apical inferior and apical lateral (42%); and mid inferior and mid inferolateral (42%) segments. Collateral connections were most prevalent between: the inferior interventricular vein (IIV) and lateral vein (64% [23/36]); and IIV and infero-lateral vein (36% [13/36]). Cross-vein microlead implantation was possible in 18 patients (90%), and single-vein implantation was conducted in the other 2 patients (10%)., Conclusions: Venous collaterals were found in vivo between LV veins in all CRT patients with evaluable venograms, making this network an option for accessing multiple LV sites using a single LV microlead.

Aims: Echocardiographic measures of dyssynchrony at baseline have not demonstrated a good ability to predict response to cardiac resynchronization therapy (CRT). The purpose of this study was to determine if the acute correction of electromechanical dyssynchrony, assessed by the change in simple pulsed-Doppler measures, was related to CRT response at 6 months., Methods and Results: Echocardiography was performed at baseline and at pre-discharge after CRT implantation. Intraventricular, interventricular, and atrioventricular dyssynchrony were evaluated by the left pre-ejection interval (LPEI), the interventricular mechanical delay, and the ratio of left ventricular filling time to RR interval, respectivelxy. A patient was considered responder if he/she was alive without hospitalization for heart failure and had an absolute increase of left ventricular ejection fraction (LVEF) >5 points. Forty-eight patients (mean age 67 ± 11 years, 73% male, mean LVEF 30 ± 5%) were included. CRT led to an acute correction of intraventricular and interventricular dyssynchrony but not to an acute correction of atrioventricular dyssynchrony. There were 31 (65%) responders at 6 months. Two factors were independently associated with CRT response in multivariate analysis: ischemic cardiomyopathy (odds ratio 0.19, 95% confidence interval 0.04-0.87; P= 0.032) and delta LPEI (odds ratio 1.03 per 1 ms decrease, 95% confidence interval 1.01-1.05; P = 0.007). By receiver operating characteristic analysis, the optimal cut-off value of delta LPEI was -16 ms. The proportion of responders in patients without ischemic cardiomyopathy and with a delta LPEI greater than -16 ms was 85%., Conclusions: Acute correction of intraventricular electromechanical dyssynchrony evaluated by the LPEI predicted CRT response at 6 months., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: We sought to determine whether atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD) and with permanent atrial fibrillation (AF) has a positive impact on ICD shocks and hospitalizations compared with rate-slowing drugs., Methods and Results: This is a pooled analysis of data from 179 international centres participating in two randomized trials and one prospective observational research. The co-primary endpoints were all-cause ICD shocks and all-cause hospitalizations. Out of 3358 CRT-ICD patients (2720 male, 66.6 years), 2694 (80%) were in sinus rhythm (SR) and 664 (20%) had permanent AF-262 (8%) treated with AVJA (AF + AVJA) and 402 (12%) treated with rate-slowing drugs (AF + Drugs). Median follow-up was 18 months. The mean (95% confidence intervals) annual rate of all-cause ICD shocks per 100 patient years was 8.0 (5.3-11.9) in AF + AVJA, 43.6 (37.7-50.4) in AF + Drugs, and 34.4 (32.5-36.5) in SR patients, resulting in incidence rate ratio (IRR) reductions of 0.18 (0.10-0.32) for AF + AVJA vs. AF + Drugs (P < 0.001) and 0.48 (0.35-0.66) for AF + AVJA vs. SR (P < 0.001). These reductions were driven by significant reductions in both appropriate ICD shocks [IRR 0.23 (0.13-0.40), P < 0.001, vs. AF + Drugs] and inappropriate ICD shocks [IRR 0.09 (0.04-0.21), P < 0.001, vs. AF + Drugs]. Annual rate of all-cause hospitalizations was significantly lower in AF + AVJA vs. AF + Drugs [IRR 0.57 (0.41-0.79), P < 0.001] and SR [IRR 0.85 (073-0.98), P = 0.027]., Conclusion: In AF patients treated with CRT, AVJA results in a lower incidence and burden of all-cause, appropriate and inappropriate ICD shocks, as well as to fewer all-cause and heart failure hospitalizations., Clinical Trial Registration: NCT00147290, NCT00617175, NCT01007474., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF), but is limited by a substantial proportion of nonresponders. We hypothesized that adding a second left ventricular (LV) lead to deliver a triple-site CRT (V 3 CRT) may improve clinical status of CRT nonresponders., Objective: We assessed the feasibility and safety of adding a second LV lead to CRT nonresponders and its clinical impact., Methods: Eighty-four recipients of a CRT system and considered as nonresponders as per clinical composite score (CCS) were enrolled in this multicenter study. They were randomized to the V 3 arm (implantation of an additional LV lead; n = 43) or control arm (no change; n = 41). Implant success rate, incidence of severe adverse events, CCS, and secondary clinical and echocardiographic end points were evaluated at 12 and 24 months., Results: Positioning of a second LV lead was successful at first (40 of 44 - 90.9%) or second (4 of 44 - 9.09%) attempt. The perioperative complication rate (infection, system explant, pneumothorax, and hematoma) was high (procedures or system-related complications for 9 patients- 20.4%). After 24 months, 35 systems (79.5%) were working properly. The multinomial logistic regression model showed that V 3 treatment had no significant influence (P = .27) on the CCS, number of HF hospitalizations, time to first HF hospitalization, New York Heart Association class, and LV ejection fraction at 12 and 24 months., Conclusion: Although addition of a second LV lead in CRT nonresponders is feasible with a high success rate, this approach is associated with a significant rate of severe adverse events and does not provide significant long-term clinical benefits (ClinicalTrials.gov Identifier No. NCT01059175)., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the impact of frailty in the elderly on response to cardiac resynchronization therapy (CRT)., Background: CRT has been shown to improve symptoms and outcome of patients with congestive heart failure (HF) and impaired left ventricular ejection fraction (LVEF). The impact of frailty on the results of CRT is unknown., Methods: Frailty defined as <14 of 17 points using the ONCODAGE (Outil de dépistage gériatrique en oncologie) G8 score was assessed before device implantation in candidates for CRT who were >70 years of age. The primary endpoint was the response to CRT, defined as an improvement of >5% of the LVEF and the absence of hospitalization for HF or cardiovascular death at 9 months., Results: Ninety-two of 151 included patients (61%) were frail, and 89 (59%) were responders. Frailty was more frequent in nonresponders: 45 of 62 (73%) versus 47 of 89 (53%) (p = 0.014) and was identified as an independent predictor of nonresponse to CRT (R = 0.30; 95% confidence interval: 0.02 to 0.59; p = 0.039). Frailty was associated with a higher cumulative probability of hospitalization for HF (log-rank p = 0.032) and of all-cause death (log-rank p = 0.033). A G8 score <10.25 correlated with hospitalization for HF or death at 9 months (area under the curve: 0.75; 95% confidence interval: 0.63 to 0.87; cutoff <10.25; 77% sensitivity, 63% specificity)., Conclusions: Frailty is as an independent predictor of nonresponse to CRT. Frail patients implanted with CRT devices have a higher risk of hospitalization for HF and mortality. Routine comprehensive geriatric assessment at the time of screening for device therapy should be recommended to optimize management. (Frailty Score Assessment for Elderly Patients Undergoing Cardiac Resynchronization Therapy [FRAILTY]; NCT02369419)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with nonischemic dilated cardiomyopathy (DCM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy (ICM). In addition, DCM has been identified as a predictor of positive response to cardiac resynchronization therapy (CRT)., Objectives: The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT, according to underlying heart disease, in a large study group of primary prevention patients with heart failure., Methods: This was an observational, multicenter, European cohort study of 5,307 consecutive patients with DCM or ICM, no history of sustained ventricular arrhythmias, who underwent CRT implantation with (n = 4,037) or without (n = 1,270) a defibrillator. Propensity-score and cause-of-death analyses were used to compare outcomes., Results: After a mean follow-up period of 41.4 ± 29.0 months, patients with ICM had better survival when receiving CRT with a defibrillator compared with those who received CRT without a defibrillator (hazard ratio for mortality adjusted on propensity score and all mortality predictors: 0.76; 95% confidence interval [CI]: 0.62 to 0.92; p = 0.005), whereas in patients with DCM, no such difference was observed (hazard ratio: 0.92; 95% CI: 0.73 to 1.16; p = 0.49). Compared with recipients of defibrillators, the excess mortality in patients who did not receive defibrillators was related to sudden cardiac death in 8.0% among those with ICM but in only 0.4% of those with DCM., Conclusions: Among patients with heart failure with indications for CRT, those with DCM may not benefit from additional primary prevention implantable cardioverter-defibrillator therapy, as opposed to those with ICM., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Despite the increasingly high rate of implantation of pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We reviewed the data regarding the applicability, safety and effectiveness of conventional pacing, ICDs and cardiac resynchronization therapy (CRT) in elderly patients. Although periprocedural risk may be slightly higher in the elderly, the implantation procedure for PMs and ICDs is still relatively safe in this age group. In older patients with sinus node disease, the general consensus is that DDD pacing with the programming of an algorithm to minimize ventricular pacing is preferred. In very old patients presenting with intermittent or suspected atrioventricular block, VVI pacing may be appropriate. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is similar in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantageous effect of the device on arrhythmic death may be attenuated by higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD implantation among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live more than 5-7years after implantation. Elderly patients usually experience significant functional improvement after CRT, similar to that observed in middle-aged patients. Management of CRT non-responders remains globally the same, while considering a less aggressive approach in terms of reinterventions (revision of left ventricular [LV] lead placement, addition of a right ventricular or LV lead, LV endocardial pacing configuration). Overall, physiological age, general status and comorbidities rather than chronological age per se should be the decisive factors in making a decision about device implantation selection for survival and well-being benefit in elderly patients., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Aims: One option to improve cardiac resynchronization therapy (CRT) responder rates lies in the optimization of pacing intervals. A haemodynamic sensor embedded in the SonRtip atrial lead measures cardiac contractility and provides a systematic automatic atrioventricular and interventricular delays optimization. This multi-centre study evaluated the safety and performance of the lead, up to 1 year., Methods and Results: A total of 99 patients were implanted with the system composed of the lead and a CRT-Defibrillator device. Patients were followed at 1, 3, 6, and 12 months post-implant. The primary safety objective was to demonstrate that the atrial lead complication free rate was superior to 90% at 3-months follow-up visit. A lead handling questionnaire was filled by implanting investigators. Lead electrical performances and the performance of the system to compute AV and VV delays were evaluated at each study visit over 1 year. The complication free rate at 3 months post-implant was 99.0% [95%CI 94.5-100.0%], P < 0.001. Electrical performances of the lead were adequate whatever the atrial lead position and remained stable over the study period. The optimization algorithm was able to compute AV and VV delays in 97% of patients, during >75% of the weeks., Conclusion: The atrial lead is safe to implant and shows stable electrical performance over time. It therefore offers a promising tool for automatic CRT optimization to further improve responder rates to CRT., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The nonresponder rate to cardiac resynchronization therapy (CRT) may be due to incomplete resynchronization, with dyssynchrony persisting in approximately 30% of patients. We hypothesized that CRT with triple-site ventricular stimulation (TRIV) may improve resynchronization and its outcomes., Objective: The purpose of this study was to assess the feasibility and safety of TRIV and collected data on clinical outcomes to dimension future studies., Methods: Our pilot randomized trial was designed to assess the safety and feasibility of TRIV with 2 right ventricular leads and 1 left ventricular leads compared to conventional CRT. The primary end-point was the rate of severe adverse events at 6 months. Secondary end-points included functional improvement parameters, quality-of-life (QOL) score, and changes of echocardiographic indices at 6 and 12 months in a subset of patients., Results: Seventy-six patients were enrolled at 11 centers and randomized to control or TRIV arm. All implant procedures but one were successful. At 6 months, there was no statistical difference between proportions of patients with at least 1 severe adverse event in both groups (34.1% vs 25.7%, P = .425). There also was no difference between functional improvement parameters, 6-minute walking distances (P = .40), QOL scores (P = .27), and echographic indices. At 12 months, the proportions of patients with a left ventricular ejection fraction gain of more than 5%, 10%, or 15% were significantly superior with TRIV., Conclusion: TRIV pacing is an effective and safe technique and may provide a greater benefit in ventricular remodeling than conventional CRT. Further studies are needed to assess its long-term benefit., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice., Methods and Results: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death., Conclusion: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In cardiac resynchronization therapy (CRT), the electrical impulse delivered by the left ventricular (LV) lead may incidentally cause phrenic nerve stimulation (PNS). The purpose of this state-of-the-art review is to describe the frequency, risk factors, and clinical consequences of PNS and to present the most recent options to successfully manage PNS. PNS occurs in 2 to 37% of implanted patients and is not always detected in the supine position during implantation. Lateral and posterior veins are at higher risk of PNS than anterior veins, and apical positions are at higher risk of PNS than basal positions. The management of PNS discovered during implantation may include mapping the course of the target vein in order to find a PNS-free site, targeting another vein if available, and pacing with alternative configurations before changing the lead location. Non-invasive options for management of post-operative PNS depend on the difference between PNS and LV stimulation thresholds and include reducing the LV pacing output, automatic determination of LV stimulation threshold and minimal output delivery by the device, increasing the pulse duration, and electronic repositioning. New quadripolar leads allow to pace from different cathodes, and the multiple pacing configurations available have proved superior to bipolar leads in mitigating PNS. This electronic repositioning addresses almost all of the clinically relevant PNS and should markedly reduce the need for invasive lead repositioning or CRT abandon, which is actually the last option for 2% of patients.

Aims: The long-term clinical value of the optimization of atrioventricular (AVD) and interventricular (VVD) delays in cardiac resynchronization therapy (CRT) remains controversial. We studied retrospectively the association between the frequency of AVD and VVD optimization and 1-year clinical outcomes in the 199 CRT patients who completed the Clinical Evaluation on Advanced Resynchronization study., Methods and Results: From the 199 patients assigned to CRT-pacemaker (CRT-P) (New York Heart Association, NYHA, class III/IV, left ventricular ejection fraction <35%), two groups were retrospectively composed a posteriori on the basis of the frequency of their AVD and VVD optimization: Group 1 (n = 66) was composed of patients 'systematically' optimized at implant, at 3 and 6 months; Group 2 (n = 133) was composed of all other patients optimized 'non-systematically' (less than three times) during the 1 year study. The primary endpoint was a composite of all-cause mortality, heart failure-related hospitalization, NYHA functional class, and Quality of Life score, at 1 year. Systematic CRT optimization was associated with a higher percentage of improved patients based on the composite endpoint (85% in Group 1 vs. 61% in Group 2, P < 0.001), with fewer deaths (3% in Group 1 vs. 14% in Group 2, P = 0.014) and fewer hospitalizations (8% in Group 1 vs. 23% in Group 2, P = 0.007), at 1 year., Conclusion: These results further suggest that AVD and VVD frequent optimization (at implant, at 3 and 6 months) is associated with improved long-term clinical response in CRT-P patients.

Left phrenic nerve stimulation is a well-known complication of cardiac resynchronization therapy (CRT). We report a case where electronic or anatomical repositioning of the left ventricular (LV) electrode (within the coronary sinus tributaries) was not feasible/effective. Surgical graft interpositioning was performed to successfully isolate the phrenic nerve from the previously implanted coronary sinus epicardial LV lead., (© 2012 Wiley Periodicals, Inc.)

Background: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V(3) is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation., Methods and Results: A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements., Conclusions: The V(3) trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT., (Copyright 2010 Elsevier Inc. All rights reserved.)