Bundle Branch Research Articles

Dual-chamber CRT-D using ICD lead implantation in the LBBAP position

Abstract Background Interest in conduction system pacing (CSP) has increased in recent years. For left bundle branch area pacing (LBBAP), 4F and 6F pacing leads have been shown to be effective and safe. No information is available on the potential use of ICD leads for LBBAP. Aim The objective of the study was to demonstrate the feasibility of implanting an ICD lead in the LBBAP position to reduce the number of leads for CRT-D therapy. Patients and Methods We implanted the 7F ICD lead in the LBBAP position through a new 10F CSP delivery sheath in ten consecutive patients. Periprocedural data, QRS morphology and degree of QRS reduction were analyzed. Results Ten consecutive patients (one female) aged 69.5±9.2 years were treated with the above-mentioned method. Eight patients had ischemic cardiomyopathy and two patients had nonischemic cardiomyopathy. All patients had a CRT-D indication. Eight patients had a wide QRS complex with complete LBB and a QRS complex of 184.8±25.8 ms. Two patients had a narrow QRS complex but first-degree AV block with a PR interval greater than 240 ms. Left ventricular ejection fraction was 31.8±8.6%. Operative and fluoroscopy times were 103.6±30.3 minutes and 10.5±6.1 minutes, respectively. On average, 1.7 ± 0.6 screwing attempts were required per patient. The intraprocedural LBBAP threshold was 0.78±0.6V/1.0ms, the impedance was 530.8±86.5 ohm, and the R-wave amplitude was 9±3.3mV. The unipolar paced QRS complex was 123.6±15.9ms, the bipolar paced QRS complex was 129.5±12.8ms, and the bipolar paced QRS complex on the next day was 133.3±11.7. The mean duration from stimulus to R-wave peak in lead V6 was 82.9 ± 19.7 ms. The R-wave interpeak interval between leads V6 and V1 was 43.4 ± 9.7 ms. All but one patient received an effective defibrillation threshold test at 30J (n=8) and 36J (n=1). One patient was not tested during the procedure due to high risk. Conclusion This first-in-human study of ICD lead implantation in the LBBAP position demonstrated its feasibility and efficacy in achieving conduction system stimulation. This approach may lead to a reduction in the number of leads implanted for cardiac resynchronization therapy. Figure 1. A- RAO view, angiography of the RV for verification of the TVA-summit. B- LAO view, angiography from the CSP- sheath after reaching final position of the LBBAP lead (right sided interventricular septum - yellow dotted line). C – 12 lead ECG (speed 50mm/sec) demonstrating paced and native QRS complexes. D – Fluoroscopy in RAO view, final result. E – Fluoroscopy in LAO view, final result. F – Transthoracic echocardiography the next day (4Ch view) demonstrates optimal LBBAP lead position.. RAO – right anterior oblique; LAO – left anterior oblique; TVA – tricuspid valve anulus; CSP – conduction system pacing; LBBAP – left bundle branch area pacing.Figure 1.

Predictors for mitral regurgitation improvement in patients with pure severe aortic regurgitation undergoing transcatheter aortic valve replacement: when can kill two birds with one stone?

Abstract Objective Transcatheter aortic valve replacement (TAVR) has been recognized as a significant treatment for pure severe aortic regurgitation (PSAR). Part of patients with PSAR concurrently suffer from functional mitral regurgitation (FMR). Whether TAVR could improve FMR in patients with PSAR and the predictors have not yet been clarified. This study aims to explore predictors of FMR improvement in patients with PSAR undergoing TAVR and subsequently provide evidence for further clinical therapy. Method Patients with PSAR and FMR who underwent TAVR at Zhongshan Hospital Affiliated with Fudan University were enrolled from June 2021 to August 2023. Depending on whether FMR improved one month post-TAVR, they were divided into groups with or without FMR improvement. The baseline data, imaging results, and follow-up data of the patients were collected. Result This study included 75 patients, among whom 38 patients had improved FMR and 37 patients did not. Compared to patients without FMR improvement, more patients in the FMR-improved group were diagnosed with renal insufficiency (10.8% vs. 0%, p=0.018), left bundle branch block (8.1% vs. 0%, p= 0.037), and less right bundle branch block (0% vs. 10.5%, p=0.017). The transthoracic ultrasound examination showed that patients with FMR improvement were prone to have lower left ventricular ejection fraction (LVEF) and larger left ventricle end dimension diastole (LVEDd). A higher proportion of patients in the FMR-improved group were found to have had more moderate to severe FMR (28.9% vs. 2.7%, P=0.029). In both groups, the degree of aortic regurgitation was significantly improved during the 1-day and 1-month follow-ups post-TAVR (p<0.001). No significant differences were found in the incidence of postoperative adverse events between the two groups during the short-term follow-up. Conclusion FMR improvement is observed in approximately half of PSAR patients undergoing TAVR. A higher FMR degree, lower LVEF, and hypertension before TAVR are independent predictors of FMR improvement.Figure 1 AR and MR post TAVRTable 1 Logistic regression

Long-term prognostic value of heart rate recovery in patients with left bundle branch block without inducible ischemia and without known coronary artery disease

Abstract Background Heart rate recovery (HRR) has been shown to predict cardiovascular and all-­cause morbidity and mortality. Left bundle branch block (LBBB) is often associated with significant heart disease and is often the result of underlying coronary artery disease (CAD), myocardial injury, strain or hypertrophy. However, there are insufficient data on the prognostic value of HRR in patients with LBBB without inducible ischemia and without known CAD. Aim The aim of this study was to determine the long-term prognostic value of HRR in patients with LBBB without inducible ischemia and without known CAD. Methods This retrospective study included 182 patients (64, 35.2% male gender, average age 63 ± 10 years) with LBBB and without known CAD who were referred to the SECHO test for chest pain. All the patients had negative SECHO test according the Bruce protocol. Risk factors for CAD (diabetes, smoking, hypertension, high cholesterol and positive family history of CAD), functional capacity (Metabolic Equivalents - METs) and heart rate recovery (HRR) were recorded in all patients. HRR was calculated as the difference between heart rate at the peak stress and heart rate in the first minute of rest. Slow HRR was defined as ≤18 beats/min. Median follow up of the patients was 102.5 months (IQR 68-146 months) for the occurrence of MACE (all-cause mortality, non-fatal myocardial infarction (MI), coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)). Results Overall, 16pts (8.8%) had slow HRR. During the follow-up period 34 out of 182 patients (18.7%) had an adverse event (16 deaths, 10 non-fatal MI, 1 CABG and 7 PCI). Using the Cox regression analysis, univariate predictors of MACE were age (B=0.050, HR 1.051 [95% CI 1.011-1.093], p=0.012), hypertension (B=-1.219, HR 3.385 [95% CI 1.071-10.699], p=0.038), MET (B=-0.183, HR 0.833 [95% CI 0.706-0.982], p=0.030), diabetes (B=0.981, HR 2.667 [95% CI 1.267-5.612], p=0.010) and slow HRR (B=1.171, HR 3.225 [95% CI 1.307-7.959], p=0.011). However, in the multivariate analysis only slow HRR remained the independent predictor of MACE (B=0.974, HR 2.648 [95% CI 0.980-7.151], p=0.048). Using the Kaplan-Meier survival curve we see that the patients with slow HRR had much shorter event-free time compared to the patients with normal HRR (106.9 ± 14.9 months vs 157.9 ± 24 months, Log Rank 7.227, p=0.007) (Figure 1.). Conclusion Slow HRR is an independent long-term predictor of adverse events in patients with left bundle branch block without inducible ischemia and without known coronary artery disease.Kaplan-Meier survival curve for the MACE

A comparative analysis of conduction system pacing and biventricular pacing in patients undergoing atrioventricular node ablation: a systematic review and meta-analysis

Abstract Background Atrioventricular node ablation (AVNA) with concomitant permanent pacemaker implantation is a well-established management strategy for patients with atrial fibrillation demonstrating refractory and uncontrolled ventricular rates. Conduction system pacing (CSP) utilising His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), has emerged as an alternative to conventional pacing (CP) (including right ventricular pacing (RVP) and biventricular pacing (BVP). The aims and objectives of this systematic review and meta-analysis is to provide a comprehensive summary and synthesis of clinical outcomes in the literature for CSP in comparison to BVP when facilitated with AVNA. Methods This study protocol was registered in the PROSPERO registry and the review was conducted as per the PRISMA guidelines. MEDLINE, EMBASE and Cochrane Library were searched for relevant studies from inception till January 11th, 2024. Results were synthesised using a random effects meta-analysis. Risk of bias (ROB) assessment was carried out with the RoB 2 and ROBINS-I tool. Results From a total of 259 references identified, 122 full texts were assessed and 5 studies (1 randomised control trial, 2 prospective observational studies, and 2 retrospective observational studies) were included in the review. A total of 738 patients (HBP-294 and LBBAP-444) received CSP and BVP implantation with AVNA, respectively. All devices were implanted successfully with a cumulative total of 4 patients in the HBP population demonstrating acute threshold hold increase following AVN. There was no loss of capture on follow-up in either treatment groups. HBP resulted in a narrower QRSd with a reduction of -35.3 ms (95% confidence interval [CI] -63.8 to -6.78; P<0.05; I2=96.6%) vs BVP. For left ventricular ejection fraction (LVEF), a weighted mean increase of 3.50% (95% CI -0.55%-7.54%; P=0.02, I2=65.8%) was observed following HBP implantation in comparison to BVP (Figure 1). Furthermore, LBBAP also demonstrated a weighted mean increase in LVEF of 6.02% (95%CI -4.05%-16.1%; P<0.05; I2=90.7%) in comparison to BVP. The mean NYHA score was reduced by -0.54 (95% CI -1.07 to -0.02; P=0.05, I2=65.5%) after HBP implantation when compared to BVP. There was a cumulative total of 45 and 65 events of heart failure associated hospitalisation in the HBP and BVP, respectively (OR 0.69; 95% CI 0.19-1.18; P=0.99, I2 =0.00). Conclusion To our knowledge, this is the first methodologically robust systematic review and meta-analysis evaluating the outcomes of CSP with AVNA. Overall, both CSP modalities demonstrated feasibility and application as an effective CRT alternative to facilitate AVNA along with a narrower QRSd ,improved LVEF and trend of better clinical outcomes. While these preliminary findings are promising, further RCTs will be necessary to establish the long-term efficacy and safety of this approach.

Impact of aortic valve calcium score on conductive disturbances after transcatheter aortic valve implantation: a monocentre retrospective study

Abstract Introduction Conductive disorders requiring permanent pacemaker implantation (PPI) remain an important issue after transcatheter aortic valve implantation (TAVI). Aims To assess the impact of aortic valve calcium score (AVCS) on conductive disorders requiring PPI after TAVI. Methods All patients who underwent TAVI with an available AVCS from the pre-procedural CT-scan report from 2016 to 2022 were included in this retrospective single-centre study. The primary endpoint was the occurrence of a conductive disorder requiring PPI at 30 days. The association between PPI and AVCS was analyzed using multivariable logistic regression and receiver operating characteristics (ROC) curves analyses. Results Seven hundred and sixty-one patients were included, of whom 125 (16%) patients required a PPI at 30 days. AVCS score was significantly higher in patients requiring PPI (3788 (2487-5218) vs. 3050 (2043-4367) AU, p<0.001). Using multivariable analysis, pre-procedural right bundle branch block (OR=6.61, 95%CI=3.82-11.5, p<0.001), first atrioventricular block (OR=1.71, 95%CI=1.03-2.83, p=0.037), the use of a self-expanding valve (OR=3.25, 95%CI=1.17-9.09, p=0.025), and AVCS >4510 AU (OR=1.83, 95%CI=1.04-3.20, p=0.035) were independently associated with PPI. The area under the curve for ACVS to predict PPI was 60.3% (95%CI=54.7%-65.9%), indicating moderate discrimination. Of note, AVCS had an incremental discriminative value (C-index 0.79 vs 0.77, LR test p=0.036) over and above traditional PPI risk factors. Conclusion The results of our study suggest that a high AVCS is associated with an increased risk of PPI after TAVI.Central illustration

Mitral regurgitation improvement following left bundle branch pacing versus right ventricular septum pacing: a dedication to postoperative amelioration of mitral regurgitation

Abstract Background Mitral regurgitation (MR) is correlated with left ventricular (LV) remodeling and LV function in patients. Left bundle branch pacing (LBBP) exhibits a significant decline in MR in left bundle branch block (LBBB) and cardiomyopathy patients. This research aims to evaluate the influence of LBBP on MR in comparison to right ventricular septal pacing (RVSP) in patients with atrioventricular block (AVB) or sick sinus syndrome (SSS). Methods Sixty consecutive patients with SSS or AVB were enrolled if they underwent pacemaker implantation via LBBP or RVSP. Patients with a history of mitral valve surgery were excluded. Echocardiogram parameters were assessed to measure MR and LV remodeling as well as LV function at baseline and follow-up. Results Thirty-six patients (60 %; mean age: 70.39 ± 14.80 years; 61.1 % male) underwent successful LBBP, and 24 patients (40 %; mean age: 71.58 ± 10.91 years; 66.7 % male) underwent RVSP. The average follow-up duration was relatively comparable between the two groups. In comparison to RVSP, LBBP demonstrated significant changes in MR area, and severity at baseline and follow-up (P<0.05). LBBP independently predicted MR amelioration in patients who underwent pacemaker implantation (HR=0.289, CI=0.087–0.9961; P=0.043). At follow-up, the LBBP subgroup with moderate/severe MR exhibited significantly shorter lead-TVA-dist, higher left atrium (LA) diameters, and mitral E/A ratio (P<0.05) compared to the none/mild MR subgroup. In LBBP with MR amelioration, LV remodeling (ΔLVEDD) was significantly enhanced compared to baseline (P=0.016). Additionally, a non-significant trend toward better improvement in LV function (ΔLVEF and ΔE/A) was observed in patients with MR amelioration. Conclusion LBBP, considered an optimal pacing technique for SSS or AVB patients, may substantially reduce MR and subsequently enhance LV remodeling and function compared to RVSP. This open, observational pilot study warrants confirmation through further investigations.Comparison between LBBP and RVSPKaplan-Meier curves for MR amelioration

Improving the yield of genetic testing in dilated cardiomyopathy using late gadolinium enhancement

Abstract Background Genetic testing has become an important tool in the work-up of dilated cardiomyopathy (DCM), aiding in family screening and providing information about prognosis and arrhythmic risk. Nonetheless, a significant proportion of patients with DCM present negative genetic test results. The "Madrid Score" was created to evaluate the likelihood of positive genetic tests and increase their yield in DCM patients. Purpose To determine if late gadolinium enhancement (LGE) assessment can improve the Madrid Score accuracy and increase the yield of genetic tests for DCM. Methods A single-centre retrospective study of patients diagnosed with DCM who underwent cardiac magnetic resonance (CMR) and genetic test between January 2017 and October 2023. The CMR imaging included the assessment of LGE. Multivariate logistic regression was performed and the model’s change in performance was evaluated when adding LGE. Results A total of 90 patients with the diagnosis of DCM underwent CMR and genetic test during the study period. Patient’s mean age was 51.0±14.6 years, and 57.1% were male. The genetic test was positive (G+) in 42 (46.7%), and negative (G-) in 48 (53.3%) patients. A variant of uncertain significance was present in 31 (34.4%), and these were included in the G- group. Most of the known independent predictors of a G+ given by the Madrid Score were significant in our cohort: Family history of DCM (OR: 4.82; CI: 1.73-11.60; p < 0.001), absence of hypertension (OR: 0.19; CI: 0.06-0.58; p < 0.001), absence of left bundle branch block (OR: 0.22; CI: 0.05-0.98; p = 0.047), and low electrocardiogram voltage in peripheral leads (OR: 3.13; CI: 0.87-11.26; p = 0.081). When analyzing the effect of LGE in the regression model (R2 = 0.622, p < 0.001), we found that the number of LGE segments (OR: 2.54; CI: 1.10-5.90; p = 0.031), and the presence of LGE in the anterior wall (OR: 3.01; CI: 1.42-12.04; p = 0.041), were associated with a higher rate of positive genetic tests. When comparing both regression models, the incorporation of LGE increased the prediction power of the standard Madrid Score, correctly predicting 82.0% of the tests in our sample, with a probability of a G+ result ranging from 2% when all predictors were absent to 84% when ≥6 predictors, including LGE, were present. Conclusion Our study suggests that LGE assessment may enhance the Madrid Score performance and consequently improve genetic testing decisions in DCM, potentially leading to better use of the limited resources in our health care system.

Myocardial single photon emission computed tomography imaging to identify non-responders to cardiac resynchronization therapy in patients with non-left bundle branch block

Abstract Background Non-response to cardiac resynchronization therapy (CRT) is an important issue in the treatment of heart failure with reduced ejection fraction (HFrEF) and non-left bundle branch block (LBBB). Although the QRS duration and morphology are crucial parameters for selecting CRT candidates, electrocardiogram (ECG) markers may inadequately represent the mechanical activation patterns within the heart. Owing to limitations associated with the ECG criteria, there is increasing interest in advanced multimodality imaging to improve patient selection. Recently, myocardial single-photon emission computed tomography imaging (G-MPI) is used for assessing left ventricular (LV) dyssynchrony. This technique is mostly automatic and has high intra- and inter-observer reproducibility and repeatability. Objectives This study aimed to examine whether preoperative G-MPI evaluation could predict non-responsiveness to CRT in patients with HFrEF with non-LBBB. Methods Between January 2021 and December 2022, 128 patients underwent CRT, of whom 73 with pre-operative evaluation using G-MPI were selected. Forty-three patients with non-LBBB (21 and 22 CRT responders and non-responders, respectively) were assessed. These patients were divided into CRT responder and non-responder groups. We evaluated the cut-off and clinical impact of pre-operative G-MPI parameters in predicting non-responsiveness to CRT. In addition, 30 patients with LBBB were analyzed. Results Among patients with non-LBBB, CRT responders and non-responders showed no significant differences in baseline characteristics, except for the LV dimension. A receiver operating characteristic curve analysis identified 108° and 27.7° as the optimal cut-offs for the bandwidth and phase standard deviation (SD), respectively, to predict non-responsiveness to CRT (area under the curve [AUC]=0.762; 95% confidence interval [CI]: 0.601–0.923 and AUC=0.742; 95% CI: 0.576–0.909, respectively). A multivariate analysis revealed that a cut-off bandwidth of ≥108° and phase SD of ≥27.7° are independent predictors of non-responsiveness to CRT in patients with non-LBBB (hazard ratios 5.65; 95% CI: 1.53–20.9; P=0.009). In contrast, there were no relationships between G-MPI parameters and non-responsiveness to CRT in patients with LBBB. Conclusions Pre-operative G-MPI findings were associated with non-responsiveness to CRT in patients with non-LBBB. The identification of potentially nonresponsive patients could influence patient management and alter outcomes.

Comparative evaluation of approach sites in right ventricular biopsy: influence on complication rates, particularly conduction defects

Abstract Background Myocardial biopsy is an essential procedure for the diagnosis of myocarditis and cardiomyopathy. As specific treatment for secondary cardiomyopathies becomes available, EMB becoming increasingly important. Although the procedure can be performed safely at institutions familiar with the procedure, some institutions tend to hesitate to perform EMB because of procedural complications. In addition, complete right bundle branch block (CRBBB) is a complication of right ventricular biopsy (RV-EMB) that occurs at a certain rate. Therefore, Patient with complete left bundle branch block (CLBBB) often exibit reluctance to undergo RV-EMB due to the risk of complete atrioventricular block. Although there are two approaches to RV-EMB, transfemoral vein and trans-intracavitary vein, and each institution is familiar with its approach, no study has ever looked at the difference in complication rates, mainly complete right bundle branch block, due to the different approach sites for right ventricular biopsy. Aims This study aims to examine the differences in complication rates, mainly CRBBB, due to differences in the approach site of the RV-EMB procedure. Methods/Results The subjects were 338 consecutive patients who underwent RV-EMB at our hospital between January 2017 and December 2022. We performed a retrospective analysis of 274 cases, excluding 43 cases that were originally CRBBB and 21 cases with ventricular pacing, ventricular fibrillation (VF), complete atrioventricular block from beginning to end, and no pre- and post-ECGs. The transfemoral venous approach group (Group TF) included 96 cases and the transjugular venous approach (Group TJ) included 178 cases, with Group TF using more warfarin (13.5% vs. 3.4%, p=0.004) and obtaining fewer specimens compared to Group TJ (3.0±1.0 vs. 3.8±0.6 pieces, p<0.001). Transient CRBBB was present in 28 (29.2%) patients in Group TF and 12 (6.7%) patients in Group TJ (p<0.001); CRBBB persisted beyond 24 hours in 8 (8.3%) and 2 (1.1%) patients, respectively. There was one case of cardiac tamponade in Group TF and two cases of VF in Group TJ, but no cases of stroke, permanent pacemaker implantation, or death. Multivariate logistic regression analysis showed that the transfemoral approach and corticosteroid administration emerged as independent predictor in the occurrence of CRBBB (p<0.001, odds ratio 0.17 and p=0.021, odds ratio 3.76, respectively.), whereas in cases of sustained CRBBB, solely the transfemoral approach stood as an independent predictor (p=0.002, odds ratio 0.07). Conclusions In RV-EMB, the transjugular venous approach has the potential to decrease CRBBB as a complication. The transjugular vein approach may be preferable in cases where complete AV block is a concern, such as patients who originally have CLBBB.

CMR characterisation of patients with heart failure and left bundle branch block

Abstract Introduction Cardiac magnetic resonance (CMR) is recommended internationally for tissue characterisation, volumetric assessment and assessment of prior myocardial infarction (1). Patients with left bundle branch block (LBBB) form a significant sub-group of individuals, however, there is limited data available to accurate determine whether LBBB is associated with any CMR-definable phenotypes. Aim We aimed to identify the distinctive cardiac magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. Methods Participants from the MATCH (MyocArdial Tissue CHaracteristics in patients with heart failure according to glycaemic status) registry were prospectively enrolled. Exclusion criteria included: LVEF >40% at initial evaluation, established diagnosis of coronary artery disease, known presence of structural heart disease, suspected myocarditis, congenital heart disease and significantly impaired renal function. Following identification of HF, guideline-directed medical therapy was initiated based on the decision of the treating physician. LV recovery was defined as achieving ≥10% absolute improvement to a level of 40% or greater of LVEF from baseline evaluation upon the date of CMR quantification. Electrocardiograms were analysed to establish the presence or absence of LBBB. Results A total of 391 patients were recruited including 115 (29.4%) presenting with LBBB. Compared to controls, LBBB patients exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8±12 vs. 38± 12 %, p=0.105) or right ventricular ejection fraction (RVEF). The prevalence of ischaemic scar (18.3% vs 21%, p=0.54), non-ischaemic fibrosis (25.2% vs 32.6%, p=0.15) and inducible ischaemia (6.1% vs. 7.6%, p=0.6) was comparable in patients with LBBB and those without. The overall rate of LV recovery was not significantly different between LBBB and non-LBBB patients (27.8% vs. 33%, p=0.32) from their baseline evaluation to the time of CMR assessment (70 [42 - 128] days). In the multivariate logistic regression, reduced LVEF remained an independent predictor of LV non-recovery in patients with LBBB, even after adjusting for gender and QRS duration (OR 0.93, 95%CI 0.87 – 0.99, p=0.03). In contrast, this association was not observed among patients without LBBB, whereas ischaemic scar was the primary predictor of LV non-recovery (OR 4.31, 95%CI 1.85 – 10.04, p=0.0007). Conclusion In this study patients presenting with a combination of HFrEF and LBBB had a larger LV cavity and smaller RV cavity than those without LBBB. However, there were no differences in the prevalence of ischaemic scar, non-ischaemic scar of inducible ischaemia according to the presence of absence of LBBB. Rates of LV recovery were similar between LBBB and non-LBBB patients.Clinical CMR ParametersSegmental Distributions

LBBAP versus conventional CRT reimplantation after transvenous lead extraction: report from a monocentric experience

Abstract Background Cardiac resynchronization therapy – defibrillator (CRT-D) reimplantation after transvenous lead extraction (TLE) can be challenging due to fibrotic remnants and absence of target veins. Left bundle branch area pacing (LBBAP) is emerging as an alternative to conventional CRT, but data is lacking about its feasibility after TLE. Purpose To explore the feasibility and safety of LBBAP as alternative to conventional CRT though epicardial pacing (EP) in patients undergoing CRT-D TLE. Methods We prospectively enrolled all patients admitted for complete CRT-D extraction and replacement from July 2022 to September 2023. At the moment of reimplantation, the choice between EP and LBBAP was made on the basis of posterolateral CS branches viability at post-extraction CS venography. Procedural success was defined as effective stimulation and absence of major complications while the primary endpoints were procedural time, QRS complex duration and electrical lead parameters. Patients undergoing LBBAP and EP reimplantation were compared. Results Twenty-six patients were enrolled (mean age 68.3 ± 7.2 years, p = 0.538; 12% females, p = 0.859). The most frequent cause of device extraction was pocket infection (58%, p = 0.773). Seventeen (65%, p = 0.783) patients had estimated high risk of procedural severe complications measured by EROS score. Overall, 80 leads were extracted. Mechanical extractors and snares were deemed necessary in 35 cases (43%, p = 0.917) and in 2 cases, respectively. Almost all patients (n=25, 96%) underwent right-sided reimplantation. Procedural success was achieved in 24 cases (92%). Compared to standard CRT through EP, LBBAP reimplantation accounted for a faster procedure (109.5 ± 34.2 vs. 126.5 ± 46.8 min; p = <0.001), less radiologic exposure (877.0 ± 234.6 vs. 1332.0 ± 515.1 sec, p <0.001) and better ventricular pacing thresholds (0.7± 0.1 vs. 1.8± 0.6 V, p <0.001). Despite a similar pre-extraction paced QRS duration (127.4 ± 13.8 vs. 133.0 ± 14.4 msec; p = 0.610), LBBAP reported significant improvement in final QRS duration (105.0 ± 13.1 vs. 127.1 ± 10.4 msec, p < 0.001) with major reduction in QRS duration (- 10.9 ± 7.5 vs - 6.8 ± 10.1, p < 0.001). Conclusion After a CRT TLE procedure, LBBAP reimplantation accounted for lower procedure duration, lower radiologic exposure, narrower QRS and lower ventricular pacing thresholds, demonstrating to be a valuable alternative to EP.

Assessment of ventricular mechanics by means of myocardial work in patients undergoing physiologic versus right ventricular apical stimulation:a prospective study

Abstract Introduction Left bundle branch area (LBBA) pacing has recently gained widespread acceptance in patients that need pacemaker (PM) stimulation. This type of physiologic pacing may improve ventricular mechanical contraction and reduce the risk of PM-induced left ventricular (LV) dysfunction. Myocardial work (MW), a new tool, based on the analysis of pressure-strain loops, combines the information from speckle tracking strain imaging and non-invasive estimate of LV pressure. It provides a better characterization of LV performance and detection of LV myocardial dysfunction. The aim of this study was to compare MW after PM implantation in LBBA pacing patients (group 1) vs right ventricular apical (RVA, group 2) pacing patients. A control group (group 3) was also enrolled for establishing MW normal values. Methods We studied 30 patients (56% females, age 80 y, IQR 75-84) who underwent PM implantation and had a high probability of a high % of stimulation and 21 controls (57% females, age 79 y, IQR 73-85, p=0.46 and p=0.73 respectively) Patients were prospectively included at two large university hospitals from March 23 until February 24. The mode of stimulation was chosen at their physician’s discretion. Exclusion criteria included LVEF <50% or significant structural or valvular disease. We compared MW parameters between group 1 and group 2 before PM implantation, and 24 hours and 3 months post PM implantation by Kruskal Wallis test. Additionally, we compared MW parameters between group 3 and PM patients after 24 hours using U Mann-Whitney test. Results The % of stimulation was 93%±12. There were no differences in baseline characteristics between group 1 (n=21, 71%) and group 2. At baseline, global work index (GWI), global constructive work (GCW), global wasted work (GWW) or global work efficiency (GWE) did not differ significantly between Group 1 and 2. At 24 hours, all the components of MW significantly improved in Group 1 and 2 and were maintained at 3 months, but the improvement was notably greater in Group 1 (see Table 1). Group 3 and PM patients were similar at baseline (HTN, 86% vs 80%, p=0.7197; DM, 29% vs 30%, p=0.91; coronary artery disease, 14% vs 10%, p=0.68; sinus rhythm, 76% vs 83%, p=0.68). Comparing group 3 and PM at 24 h, GWI, GCW, GWE was significantly higher in group 3 (p=0.0023, p=0.009, p=<0.0001) and GWW was significantly lower (p=<0.0001). Regarding the type of stimulation, MW parameters values in Group 1 were still lower than in Group 3 but clearly better than Group 2 values (see Figure 1). Discussion Our results showed that MW parameters improved to a greater extent in LBBA compared to RVA pacing immediately and after 3 months of PM implantation. Compared to our control group, LBBA pacing group achieved better performance than RVA pacing patients, yielding a more coordinated LV contraction. Nevertheless, more studies are needed to clarify if LBBA pacing causes less PM induced LV dysfunction compared to RVA pacing.

Can variants of genes associated with familial heart block predict conduction disease in the general population? A UK Biobank study.

Abstract Background Progressive familial heart block is a genetic disease that can present with worsening cardiac conduction disease (CCD) and risk of life-threatening bradycardia. The prevalence, penetrance, and expressivity of known rare pathogenic/likely pathogenic variants (P/LP) in the general population is unclear. In addition, the role of common genetic variation in this phenotypic expression is unknown. Understanding this is essential for patient management in clinic. Purpose 1). To investigate the prevalence of variants linked with early-onset CCD and phenotypic expression in a large biobank. 2). To investigate whether a PR interval polygenic risk score (PRS) improves risk prediction. Methods Early-onset conduction disease P/LP or variants of uncertain significance (VUS) were identified from ClinVar, genetic testing reports at a teaching hospital (6 variants), and the literature, mapping to 22 genes. From the full UK Biobank prospective cohort, 469,511 participants passed genetic quality control and were assigned to P/LP, VUS, or genotype negative (G-) groups, using whole exome sequencing analysed with bcftools. A PR-PRS was constructed using weights from a published meta-analysis excluding UKB data. The primary outcome was CCD (atrioventricular (AV) block, bundle branch block, pacemaker or ICD implantation) and secondary outcomes were high-grade AV block or pacemaker insertion, compared with lifetime risk Cox proportional hazards controlled for sex and age as a timescale. Results 55% of participants were female, 95% had European ancestry, and average age at censor was 71 years. There were 25 P/LP carriers, and 8,862 with a VUS, in 6 genes (MYH7, SCN5A, TNNI3K, TRPM4, TTN, and LMNA). Major demographic factors were the same between groups. CCD was significantly more prevalent in P/LP individuals (28% vs 5.8% in VUS vs 5.5% in G-; p<0.001) with a hazard ratio of HR 6.47 [95% CI=3.09-13.6] vs G-. This was driven by AV block and pacemaker implantation (HR 23.2 [95% CI=8.69-61.8] and 13.4 [95% CI=6.01-29.8], respectively). Results were similar in an unrelated subset and controlling for ischaemic heart disease and heart failure. The 7 P/LP individuals with conduction disease were mostly linked to a single LMNA variant (4 out of 6 carriers with penetrant disease). In the full cohort, the PR-PRS was predictive of CCD (HR=1.07 [95% CI=1.06-1.08]), AV block (HR=1.09 [95% CI=1.06-1.13]), and pacemaker implantation (HR=1.04 [95% CI=1.02-1.06]). When combined with P/LP status, both PR-PRS (HR=1.07 [95% CI=1.06-1.08]) and P/LP (HR=6.42 [95% CI=3.06-13.5]) were independent predictors of CCD. Conclusion(s) Rare variant carrier status predicts a 6.5-fold increased lifetime risk of CCD, a 23-fold increased risk of AV block and 13-fold risk for pacemaker requirement. However, phenotypic expression for some variants is highly variable. A PR-PRS captures risk independent of P/LP variants and warrants further investigation with updated PRS construction methods.

Conduction-System pacing Italian Network Group (C-SING): insights from a Nationwide Multicenter Observational Study

Abstract Background/Introduction Conduction system pacing (CSP), encompassing His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has gained prominence in treating bradycardia and heart failure in recent years. Despite its increasing utilization, data on real-world adoption of CSP are limited. Purpose The C-SING study aimed at assessing patient characteristics, implant success, procedural details, and safety of CSP when performed in routine clinical practice. Methods Periprocedural data from 27 experienced CSP centers across Italy were collected on patients undergoing CSP implantation for various indications between January 2021 and January 2024. Results The study comprised 1,317 patients (median age 78 years [interquartile range, 71-83], male 66.2%). Leading indications included atrioventricular (AV) block (40.8%), sinus node dysfunction (12.1%), atrial fibrillation with bradycardia (9.7%), AV node ablation (9.5%), and heart failure (12.5%). Pacemakers were implanted in 77.3% of patients, cardiac resynchronization devices in 21.7%, and implantable cardioverter-defibrillators in 1.0%. Stylet-driven and lumenless CSP leads were utilized in 64.7% and 35.3% of procedures, respectively. Final 12-lead ECG assessment revealed LBBAP capture in 88.7% patients, HBP in 8.4% (selective 4.2%, non-selective 4.2%), and no CSP capture in 3.0%, resulting in a 97.0% CSP lead implantation success rate. In patients with LBBAP, predominant capture types were left bundle branch pacing (19.6%), left posterior fascicular pacing (19.2%), and left septal fascicular pacing (14.8%). Comparing HBP to LBBAP, the latter showed shorter procedural time (60 minutes [45-80] vs. 70 minutes [60-95], p=0.003), but similar fluoroscopy time (6.0 minutes [3.3-10.8] vs. 6.1 minutes [4-10], p=0.735). Paced QRS duration was longer in LBBAP (118 ms [105-130]) compared to HBP (110 ms [101-122], p<0.001). LBBAP showed lower capture thresholds (0.6 V [0.5-0.9] @0.4 ms vs. 0.8 V [0.5-1.5] @1.0 ms, p<0.001) and higher R-wave sensing (10.7 mV [8-16] vs. 4.5 mV [2.4-9.9], p<0.001). The rate of periprocedural complications was higher in patients with LBBAP than HBP (7.3% vs. 1.8%, p=0.03), with the most frequent events being intraprocedural perforation into the left ventricular cavity during lead screwing (2.6%) and CSP lead dislodgment before hospital discharge (1.4%). These occurrences necessitated lead repositioning without additional complications. Conclusion CSP demonstrated feasibility as a primary pacing strategy for various indications in a real-world, multicenter setting. LBBAP, more frequently used than HBP, exhibited shorter procedural time and superior acute electrical parameters. LBBAP revealed a higher rate of minor procedural complications than HBP. Further investigations, supported by additional long-term outcome data, are essential to comprehensively assess CSP performance.

The association between exercise-induced ventricular premature contractions and long-term mortality in patients without coronary artery disease

Abstract Background/Introduction The treadmill exercise test is widely used clinical test to determine cardiovascular risk and mortality, regardless of clinical risk factors (1). ST-segment changes detected in the exercise test are shown to predict myocardial ischemia (2) and premature ventricular complexes (PVCs) are frequently observed during exercise stress testing (3). Exercise-related PVC is observed in 14% to 23% of healthy individuals without significant heart disease (4,5). The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial. Purpose Therefore, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients who had been diagnosed with non-obstructive coronary artery disease after coronary angiography. Methods The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on coronary angiogram from January 2016 to April 2021. Patients with previous history of coronary revascularization, previous myocardial infraction, heart failure, moderate or severe heart valve disease, congenital heart disease, cardiomyopathy, bundle branch block, and left ventricular hypertrophy were excluded from the study. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase. Results The long-term mortality was observed in 53 patients out of 1624 patients in the mean follow-up of 47 months. PVCs was observed in 293 (18.7%) patients without long-term mortality, while PVCs was observed in 24 (45.3%) patients with long-term mortality (p<0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase (p<0.007, HR (95% CI) 2.244 (1.244 – 4.047)) and advanced age (p<0.001, HR (95% CI) 1.194 (1.143 – 1.247)) were associated with long-term all-cause mortality (Figure 1). Considering Kaplan-Meier curve, individuals with PVCs in recovery had significantly higher risk of long-term mortality compared with those with without PVCs (log-rank statistic: 22.47, p<0.001) (Figure 2). Conclusion(s) The study highlights that PVCs monitored in the recovery phase of the treadmill exercise test were associated with long -term mortality in patients without structural heart disease and coronary artery disease.Figure 2Figure 1

Characteristics associated with prevalent atrial fibrillation and risk profile for future atrial fibrillation among those in sinus rhythm in an elderly population in the ELSA Brasil Study

Abstract Background Atrial fibrillation (AF) is an arrhythmia that can lead to limiting symptoms and increases the risk of stroke and heart failure (HF). Purpose To evaluate the association of clinical, electrocardiographic, and echocardiographic parameters with prevalent AF or flutter (AFF), and the risk profile for future AFF according to Charge-AF and EHR scores in an elderly population. Methods The ELSA-Brasil is a prospective cohort study designed to investigate cardiovascular disease and diabetes in 15,105 men and women, civil servants from universities or research institutions in six cities of Brazil. We included all participants in ELSA-Brasil aged 60 and over whose diagnosis of AFF could be assessed and had echocardiography performed at the study's baseline. From the initial sample with participants ≥ 60 years (n = 3,263), 400 participants were excluded due to missing data about AFF, and 775 who did not have echocardiographic studies. Results There were 88 (4.2%) participants with AFF at baseline among the 2,088 (65 ± 4.1 years; 53% women) included in this analysis. Those with AFF were older (66.8 ± 4.4 vs 65 ± 4.0 y-o) and had a higher prevalence of HF (16% vs 3.1%), previous myocardial infarction (14.8% vs 3.8%), left bundle branch block (LBBB: 4.6% vs 0,9%), prolonged QT interval (7.9% vs 2.0%), supraventricular extrasystoles (4.6% vs 1.2%), and sinus bradycardia (11.3% vs 2.9%). AFF individuals also presented larger left atrial volume index - LA (33.3 mL/m2 versus 27 mL/m2), left ventricular end-diastolic diameter (4,63 ± 0,6 cm versus 4,47 ± 0,4 cm) and lower left ventricular ejection fraction (LVEF: 63.6 ± 9.1% vs 67.4 ± 6.4%) that non-AFF (all p-values <0.05). In multivariable analysis, prevalent HF, LBBB, larger LA, and lower LVEF were independently associated with the presence of AFF. Among those in sinus rhythm at study baseline, both risk models showed that most individuals in our sample were at low risk. In the Charge-AF, 63% of individuals were identified as presenting low risk (<2.5%), and 12% of the sample was categorized as high risk, with a risk of five-year AFF greater than 5%. Similarly, in the EHR, 67% of participants were classified as low risk, and 13% were considered high risk. Conclusion We found that AFF was present in 4.2% of the subset of older participants in a cohort composed of free-living individuals in Brazil. The presence of AFF was associated with HF history, altered cardiac electrical activity, LA dilation, and worse LV systolic function. Among those with sinus rhythm, 12-13% were considered at high risk of developing AFF (> 5% in five years) based on two clinical scores. Clinical surveillance and monitoring of electrocardiography and echocardiography parameters may help the early identification of risk factors for AFF.

Assessment of mechanical dyssynchrony can improve the new ESC-2021 guidelines for cardiac resynchronization therapy

Abstract Background In 2021, new guidelines for cardiac resynchronization therapy (CRT) were published by the European society of cardiology (ESC-2021), where the different classes of recommendations were based on a new ECG-based definition of left bundle branch block (LBBB). However, its association with reverse LV remodeling and additive prognostic value remain unknown. Aim To investigate (1) the association between the ESC-2021 CRT guidelines and reverse LV remodeling at follow up, and (2) the additive prognostic value of baseline assessment of mechanical dyssynchrony to the ESC-2021 guidelines. Methods We investigated 244 heart failure patients in sinus rhythm treated with CRT in two European centers. 70% of the population were males. Mean age was 69 ± 10 years, QRS duration: 154 ± 24 msec. Mechanical dyssynchrony at baseline was defined as the presence of apical rocking or septal flash (ApRock/SF) in 2D transthoracic echocardiography. LV volumes were measured at baseline and at 12 ± 6 months after CRT, where the amount of CRT induced reverse LV remodeling was calculated as the percent change of LVESV at follow-up compared to baseline. Results Applying the ESC-2021 LBBB definition, only 18% (n=45) of patients had LBBB. Applying the guidelines, only 14% (n=35) had class I recommendation (LBBB + QRS ≥ 150 msec), 44% (n=107) had class IIa (LBBB + QRS 130-149 msec or non-LBBB + QRS ≥ 150 msec), 29% (n=70) had class IIb (Non-LBBB + QRS 130-149 msec), and 13% (n = 33) were not recommended according to the ESC-2021 because of having baseline QRS duration between 120 and 129 msec. On the other hand, ApRock/SF was evident in 57% (n=140) of the patients. There was non-significant difference in the relative decrease in LVESV at follow up between patients with LBBB and non-LBBB applying the new LBBB definition (44% [IQR: 32-63], vs. 39%, IQR [20-57], P = 0.08, panel A). Similarly, there was no significant difference in the relative decrease in LVESV at CRT follow up among the four guideline recommendation classes, panel B. We combined presence of mechanical asynchrony at baseline with each of the guideline recommendation classes. The combination of ApRock/SF with classes IIa and IIb improved the prediction of reverse LV remodeling significantly (P<0.001 and <0.01 respectively), while adding mechanical asynchrony did not significantly improve prediction in the class I and the not-recommended subgroups. However, results of these last 2 may have been impacted by a small number of patients, panel C. Conclusion The new ESC-2021 definition of LBBB is associated with few patients with LBBB and consequently small number of patients with class I recommendation according to the new guidelines. There was weak association between the new ESC-2021 guideline classes of recommendation and reverse LV remodeling after CRT. However, baseline assessment of ApRock and SF can significantly improve the guidelines in predicting CRT outcome.

Cusp-overlap technique to reduce permanent pacemaker implantation rate after transcatheter aortic valve implantation

Abstract Background Persistent conduction disturbances requiring permanent pacemaker (PPM) implantation are one of the most common complications after Transcatheter Aortic Valve Implantation (TAVI). Cusp-Overlap Technique (COT) is a novel approach for self-expandable valve implantation to minimize the rate of procedural complications, mainly PPM implantation. Purpose To determine if the COT during TAVI with self-expandable valves leads to a reduction of PPM implantation rate in the real-world setting. Methods A retrospective analysis of consecutive patients undergoing TAVI between January 2020 and November 2023 in one high-volume tertiary care center in Portugal was conducted. Two groups were defined, the COT group and the control group based on the fluoroscopic approach. A baseline comparison between the 2 groups was made using independent-samples t-test and chi-square analysis to determine if there was a difference between the prevalence of known risk factors for PPM implantation after TAVI. Afterwards, chi-square analysis was used to determine if COT led to a reduction in the PPM implantation rate. Results Of the 539 completed procedures in this timeframe, 289 were excluded due to previous pacemaker implantation, use of a valve not amenable to COT or valve-in-valve implantation. COT was used in 57.6% of eligible cases. Baseline comparison did not show a significant difference in the prevalence of several known risk factors for PPM implantation, including complete right bundle branch block, atrio-ventricular block, calcium score, aortic ring dimensions and pre/post-dilation. PPM implantation after TAVI was required in 31.6% of cases. In the COT group the PPM implantation rate was 22.9% and in the control group 43.4%. Chi-square analysis showed a very statistically significant difference between the 2 analyzed groups (p-value = 0.001). Conclusion PPM implantation remains a frequent complication of TAVI. However, this study showed that the utilization of COT leads to a reduction of the PPM implantation rate.

Clinical validation of the 2021 European Society of Cardiology guidelines on pre-existing right bundle branch block patients undergoing transcatheter aortic valve replacement

Abstract Introduction The management of patients with right bundle branch block (RBBB) undergoing transcatheter aortic valve replacement (TAVR) remains challenging. In these patients, the 2021 ESC guidelines recommend early pacemaker (PM) implantation in case of PR prolongation, QRS axis change or transient high-degree atrioventricular block (HAVB). However, evidence for the proposed criteria is scarce. Purpose Our aim was to evaluate the ESC recommendation for risk stratification of RBBB patients undergoing TAVR. Methods We retrospectively analyzed patients with pre-existing RBBB undergoing TAVR at our institution between 2011-2023. A surface 12-lead electrocardiogram (ECG) was available before and after procedure in all patients. The following, proposed ESC criteria were validated: ΔPR interval ≥ 20ms, QRS axis change or transient HAVB < 24 hours after TAVR. Results Of a total 1412 patients undergoing TAVR, 109 had pre-existing RBBB and were eligible for final analysis (mean age 83±5 years, 39% female). Of 109 RBBB patients, 36 (33%) developed persistent HAVB and received a permanent PM. Among the other 73 patients (67%), 17 patients (23%) suffered delayed HAVB during 30-days FU. When applying the ESC Guidelines, PM placement would have been indicated in 52% (38/73) of patients with RBBB after TAVR: due to transient HAVB in 17 (23%), due to PR prolongation ≥ 20ms in 19 (26%) and due to QRS axis change in 20 patients (27%). The proposed ESC criteria identified 82% of patients (14/17) with delayed HAVB during 30-day FU, while missing 3 patients (18%, 2.8% of overall cohort, Figure). This resulted in a sensitivity of 82% and a negative predictive value of 91%. Among the 17 patients with delayed HAVB, 12 patients (71%) displayed transient atrioventricular (AV) block within 24 hours after TAVR. Conclusion In this large cohort of RBBB patients undergoing TAVR with contemporary valves and techniques, the proposed ESC criteria of PR prolongation, QRS axis change or transient HAVB correctly identified 4/5 patients developing HAVB during 30-day FU. Prospective studies are warranted to confirm these findings.

Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)

Abstract Background Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients. Purpose To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB Methods Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database. Results (Table) N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF. Conclusions In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table