AIMS:This study aimed to determine optimal atrioventricular (AV) timing for left bundle branch area pacing (LBBAP) and optimal AV and interventricular (VV) timing for LBBAP optimized cardiac resynchronization therapy (LOT-CRT) to enhance the benefit of conduction system pacing. METHODS AND RESULTS:Acute measurements of LV dP/dtmax and QRS duration were collected during sweeps of AV and VV delays during paired comparison of LBBAP, LOT-CRT, and biventricular pacing (BVP) in 48 CRT-indicated patients. Optimal AV delays were selected as the vertex of a parabolic model fit to the AV sweep results, obtained independently for LV dP/dtmax and QRS duration. LBBAP, LOT-CRT, and BVP were similarly sensitive to the choice of AV delay, and 60 ms deviations from optimal AV delay resulted in an approximately 30% reduction in the haemodynamic benefits of resynchronization. Based upon LV dP/dtmax measurements, the average optimal paced AV (PAV) for LBBAP (152 ms) was significantly shorter than that for LOT-CRT (171 ms, P < 0.01) or BVP (167 ms, P = 0.01). Based upon QRS duration, the average optimal PAV for LBBAP (164 ms) was similar to that for LOT-CRT (160 ms, P = 0.52) or BVP (165 ms, P = 0.95). For each resynchronization modality, a linear regression between the patient's measured intrinsic AV conduction and their optimal AV delay provided a patient-specific AV delay, resulting in improved AV selection compared to applying a fixed AV delay to all patients. Finally, simultaneous activation (VV = 0) was best for both LOT-CRT and BVP. CONCLUSION:LBBAP, LOT-CRT, and BVP are similarly sensitive to AV-timing. Optimal AV delay is linearly related to intrinsic AV for each resynchronization modality. For LOT-CRT and BVP, simultaneous biventricular activation is best on average. CLINICAL TRIAL REGISTRATION INFORMATION:https://clinicaltrials.gov/study/NCT04905290.

There are many factors contributing to the failure of conventional CRT with biventricular pacing, including coronary anatomy and an inability to stimulate diseased tissue. In this paper, we review evolving conduction system pacing (CSP), a physiological alternative to conventional CRT. CSP allows correction of bundle branch block and provides new opportunities to address multiple limitations of conventional CRT. Further studies are required to determine how the techniques are best applied in specific clinical situations.

BACKGROUND:Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes. OBJECTIVE:The aim of the study was to compare the clinical outcomes between BVP and LBBAP in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT. METHODS:This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June 2023. The primary outcome was a composite of all-cause mortality or first heart failure hospitalization (HFH). Secondary outcomes included separate analyses of HFH and all-cause mortality. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves, Cox proportional hazards models, and competing risk analyses were performed. RESULTS:A total of 2579 patients were included (BVP, 1118; LBBAP, 1461). In the propensity score-matched cohort (BVP, 780; LBBAP, 780), LBBAP demonstrated shorter paced QRS duration (129 ± 19 ms vs 143 ± 22 ms; P < .001). LBBAP was associated with a significantly lower risk of the composite primary outcome (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-0.98; P = .048) and reduced HFH (HR, 0.63; 95% CI, 0.49-0.82; P < .001). No significant difference in all-cause mortality was observed (HR, 0.82; 95% CI, 0.63-1.07; P = .156). Procedural complications were lower with LBBAP (3.5% vs 6.5%, P = .004). CONCLUSION:LBBAP was associated with superior electrical resynchronization, fewer HFHs, and lower procedural complications compared with BVP in patients with LVEF <50% requiring CRT. Randomized trials are needed to confirm long-term benefits.

BACKGROUND:Traditional cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) may be less effective in patients with nonspecific intraventricular conduction delay (NIVCD). Left bundle branch area pacing (LBBAP) combined with left ventricular (LV) coronary venous lead pacing (LOT-CRT) may be more effective in these patients. OBJECTIVE:We assessed the echocardiographic response of LOT-CRT in patients with left bundle branch block (LBBB) or NIVCD and compared it with a propensity-matched BVP cohort. METHODS:Patients with conventional CRT indications and preferentially NIVCD were recruited. Echocardiographic parameters, including absolute percentage change in LV ejection fraction (LVEF) and relative percentage change in LV end-systolic volume (LVESV), were evaluated at implantation and 6-month follow-up. The BVP cohort was from an independent study, selected using 1:1 propensity-matching. LOT-CRT patients were subclassified into "successful LOT-CRT" (LBBAP; presence of r' in electrode electrocardiography [ECG] V1) and "deep septal optimized therapy" (DOT-CRT) (functional deep septal capture). RESULTS:LOT-CRT patients (N = 34; age 64 years, women 38%, NIVCD 47%, LBBB 53%, implantable cardiac monitor 21%, QRSd 175 ms, and LVEF 27.6%) had significantly greater LVEF improvement (16.1% vs 6.1%; P <.01) and LVESV reduction (-43.5% vs -20.9%; P <.01) compared with BVP patients. After adjusting for baseline characteristics, LOT-CRT patients still had significantly greater LVEF improvement (7.5%; P <.01) and LVESV reduction (18.4%; P <.01) than BVP patients. The response was consistent across LBBB and NIVCD subgroups. LOT-CRT patients with QRS ≥ 171 ms showed greater benefit (P = .04; both LVEF and LVESV). No significant differences were observed between successful LOT-CRT and DOT-CRT. CONCLUSION:LOT-CRT resulted in superior LVEF and LVESV improvements compared with BVP in NIVCD and LBBB patients and enhanced CRT response.

Traditional cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) may be less effective in patients with nonspecific intraventricular conduction delay (NIVCD). Left bundle branch area pacing (LBBAP) combined with LV coronary venous lead pacing (i.e., LOT-CRT), may be more effective in these patients. We aimed to assess the six-month echocardiographic response of LOT-CRT in those with left bundle branch block (LBBB) versus IVCD and compare the response to a contemporary propensity-matched BVP cohort. Patients undergoing conventional CRT indications were enrolled. Echocardiographic parameters, including absolute % change in LV ejection fraction (LVEF) and relative % change in LV end-systolic volume (LVESV), were assessed prior to implantation and 6 months postoperatively. The BVP cohort was from an independent (contemporary) study of CRT indicated patients, selected according to 1:1 propensity score matching. The propensity model was a logistic regression that included age, sex, ischemic cardiomyopathy, QRS duration, conduction disease, and LVESV as predictors. For the LOT-CRT patients, conduction system pacing (CSP) capture type was adjudicated, and patients were further divided into "successful LOT-CRT" (i.e. LBBAP capture subtype) and "DOT-CRT" (i.e. deep septal capture subtype; no terminal r/R’ in V1). Baseline demographics of LOT-CRT cohort (N=34) were (mean); age 64 y, female 38%, NIVCD 47%, LBBB 53%, ICM 21%, QRSd 175ms and LVEF 27.6%. LOT-CRT patients had a larger absolute increase in LVEF (16.1% vs 4.9%; p<0.01) and a larger percent change in LVESV (-43.5% vs -19.5%, p<0.01) compared to the matched BVP patients (see Figure top green lines). Sub-classification into LBBB or NIVCD showed no differences in either LVEF or LVESV change for the LOT-CRT cohort, while the BVP cohort showed significantly lower LVEF response in NIVCD patients (see Figure). Among the LOT-CRT patients, no statistically significant difference was found between those with "successful LOT-CRT" (N=18) and "DOT-CRT" (N=15) in LVEF change (13.5% vs 20.7%; p=0.13) or LVESV change (-42.6% vs -46.2%; p=0.67). Moreover, multivariate analysis of LVEF and LVESV improvement in response to LOT-CRT showed no significant effects within the different conduction disease types (p=0.90 and p=0.75, respectively) or CSP capture types (p=0.74 and p=0.33, respectively). Compared to a matched historical BVP cohort, LOT-CRT patients showed a significantly larger improvement in LVEF and in LVESV after 6 months in both LBBB and IVCD patients suggesting that placement of an LBBAP lead rather than a traditional RV lead may augment response in CRT patients. In this analysis, the presence of a terminal r/R’ in V1-ECG in LOT-CRT recipients was not a prerequisite for the larger echocardiographic response observed.BVP vs LOT-CRT response in LBBB or NIVCD

The optimal timing for initiating direct oral anticoagulants (DOACs) for secondary stroke prevention in patients with atrial fibrillation and acute ischaemic stroke remains controversial due to concerns about haemorrhagic transformation. This study aimed to analyse the efficacy and safety of early versus late DOAC initiation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted, searching major databases (PubMed, Embase, Cochrane Library and ClinicalTrials.gov) up to May 2024. A total of 11 studies were identified, comprising nine cohort studies (75.5% weight) and two randomised controlled trials (RCTs) (24.5% weight), involving 13 020 participants. The early DOAC group (mean initiation 3.5±1.29 days) included 6250 participants, while the late group (5.7±1.25 days) had 6770 participants. Outcome measures included recurrent ischaemic stroke (RIS), intracranial haemorrhage (ICH), systemic embolism, major haemorrhage (MH), non-major haemorrhage (NMH) and all-cause mortality. Statistical analysis using the Cochrane Review Manager calculated ORs and 95% CIs via the Mantel-Haenszel random effects model. This pooled meta-analysis revealed that the early DOAC group had lower rates of RIS (2.2% vs 2.9%, OR 0.72, 95% CI 0.52 to 0.98, p=0.04, I2=40%) and ICH (0.51% vs 0.93%, OR 0.45, 95% CI 0.29 to 0.70, p<0.05, I2=0%) compared with the late DOAC group. Subgroup analysis of RCTs and cohort studies showed reduced RIS and ICH risks in the early DOAC group, with moderate heterogeneity. In the sensitivity analysis, the early group (<4 days) had a lower risk of RIS compared with the late group (>4 days) without a statistically significant impact on ICH. No significant differences in MH, NMH, systemic embolism or all-cause mortality were observed between either group; however, a limited number of RCTs and moderate heterogeneity weakened the conclusions. Additional RCTs are needed to provide more definitive insights.

The terminology of second-degree atrioventricular block has evolved over time, thereby creating some confusion and misinterpretations. Strict adherence to standard terminology and the appropriate use of eponyms are important to avoid diagnostic errors.

Background: Prior research has linked cardiovascular diseases with higher COVID-19 mortality and worse hospital outcomes, particularly in severe heart failure. Large population-based data regarding the impact of preexisting ischemic heart disease (IHD) on COVID-19 outcomes is not well established. Objective: To study the impact of COVID-19 infection on IHD hospital mortality and other outcomes. Methods: The study included a patient cohort from the 2020 and 2021 National Inpatient Sample (NIS) database. Propensity score matching was used to match the study cohort (COVID-19 with IHD) to controls (COVID-19 without IHD) using a 1:1 matching ratio. The outcomes analyzed were in-hospital mortality, rates of acute kidney injury (AKI), acute myocardial injury (AMI), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, pulmonary embolism (PE), ventricular tachycardia (VT), ventricular fibrillation (VF), length of stay (LOS), and total hospitalization charges. Results: A total of 2,532,652 patients met the inclusion criteria (1,199,008 females [47.3 %), predominantly Caucasian 1,456,203 (57.5 %); mean [SD] age 63, (5.4), including 29,315 (1.1 %) patients with a history of IHD. Following propensity matching, 4,772 COVID-19 patients with and without IHD were matched. IHD patients had higher rates of AMI (adjusted odds ratio (aOR) 3.75, 95 % CI 3.27-4.31, p < 0.001), cardiogenic shock (aOR 2.89, 95 % CI 1.60-5.19, p < 0.001), VT (aOR 3.26, 95 % CI 2.48-4.29, p < 0.001), and VF (aOR 2.23, 95 % CI 1.25-3.99, p < 0.001). The odds ratios of in-hospital mortality, AKI, PE, mechanical ventilation, tracheal intubation, and resource use were not significantly different. Conclusion: A history of IHD does not impact COVID-19 mortality but increases the risk of in-hospital cardiac complications.

Background: Rate and rhythm controlling therapy in patients with atrial fibrillation (AF) are theoretical concepts, however, in clinical practice there is a substantial overlap between these strategies. AV junctional (AVJ) ablation is the ultimate form of rate control; however, it may result in rhythm control as well. Hypothesis: We hypothesize that individuals that underwent AVJ ablation for AF have a decrease in their AF burden after the procedure. Goals: The purpose of our study was to determine the outcome of AVJ ablation in patients with AF, in respect to atrial rhythm and AV synchrony. Methods: Retrospective review of AF patients that underwent AVJ ablation with prior or de novo conduction system pacing (CSP) lead. Included were only patients with a cardiac monitor/device allowing assessment of AF burden prior to AVJ ablation. Results: Thirty-six patients were identified, age 74±5 years, 14 male (39%), 15 paroxysmal AF (42%), 10 persistent AF (28%), 11 longstanding persistent AF (31%). 25/33 patients (76%) had a history of AF ablation. All patients underwent implantation of, or had a prior, CSP lead [His bundle pacing n=11 (31%), LBBAP n=25 (69%)]. The heart rate decreased from 89±28 bpm pre procedure to 78±7 bpm post-AVJ ablation, p=0.01. The spontaneously conducted QRS complex prior to AVJ ablation was 116±34 ms and the QRS during CSP after AVJ ablation was 129±25 ms, p=0.02. In the entire population, AVJ ablation resulted in a reduction of AF burden from 69±40% to 48±49%, p=0.005. Of those with persistent and longstanding persistent atrial fibrillation, 5/21 patients (24%) restored normal sinus rhythm without other intervention following AVJ ablation. Of those patients that spontaneous restored normal sinus rhythm, 3/5 had prior ablations (60%). During a follow-up of 703±524 days, LV EF improved from 42±16% to 47±13%, p=0.01 . Conclusion: Although AVJ ablation is the ultimate form of rate controlling therapy, in the era of CSP it may also result in better rhythm control in a substantial number of patients. Therefore, implantation of an atrial lead and avoidance of placing the CSP lead in the atrial channel may be advisable to assure AV synchrony.

BackgroundCardioneuroablation(CNA) targeting ganglionated plexi has shown promise in treating vasovagal syncope. Only radiofrequency ablation has been used to achieve this goal thus far.ObjectiveWe investigated the utility of cryo-balloon ablation(CBA) of the pulmonary veins as a potential simplified approach to CNA.MethodsWe are reporting our observations of autonomic modulation in a series of 17 patients undergoing CBA for atrial fibrillation and our early experience using CBA of the PVs in 3 patients with malignant vagal syncope.ResultsIn 17 patients undergoing CBA of AF, sinus cycle length was recorded intra-procedurally after ablation of individual PVs. We demonstrated most pronounced shortening of the sinus cycle length after isolation of the right upper PV which was ablated last. There was reduced SNRT and AV nodal ERP after CBA. The elevation in resting heart rate by 6-7 beats/minute following CBA persisted during a follow-up of 12 months. We performed CBA of the PVs in 3 patients with recurrent vagal syncope mediated by sinus arrest (n=2) and AV block (n=1). In all patients, isolation of the right upper PV resulted in marked shortening of sinus cycle length. During a follow-up of 178±43 days (134-219 days) CNA resulted in abolition of pauses, bradycardia related symptoms and syncope in all patients.ConclusionCBA of the PVs (most importantly the right upper PV) may be a predictable anatomic CNA approach in patients with refractory vagal syncope due to sinus arrest and/or AV block and may deserve systematic investigation as a tool to perform CNA.