Left bundle branch area pacing using a lumenless lead: A systematic literature review and meta-analysis.

BACKGROUND: Although left bundle branch area pacing (LBBAP) has been shown to be a feasible option for delivering physiological pacing, data are largely limited to single-center reports. The aim of this analysis was to systematically assess the safety and efficacy of LBBAP with the Model 3830 lead among primarily bradycardia patients. METHODS AND RESULTS: PubMed, Embase, Cochrane Library, and Google Scholar were searched for full-text articles on LBBAP using the SelectSecure Model 3830 lumenless lead. Rates and means were estimated using random- and mixed-effects models. Of 3395 articles, 53 met inclusion criteria, representing 6061 patients undergoing an implant attempt. Average patient age was 68.1 years (95% CI: 66.6, 69.6) and 53.1% were male (95% CI: 50.5%, 55.7%). The average implant success rate among bradycardia-indicated patients was 92.7% (95% CI: 89.5%, 94.9%). The overall estimated procedural adverse event rate was 2.5% (95% CI: 1.1%, 5.4%). The estimated septal perforation rate at implant was 1.6% (95% CI: 1.0%, 2.6%) with no adverse clinical sequelae reported. Pacing thresholds were low at implant (0.67 V [95% CI: 0.64, 0.70]) and remained stable through 12 months (0.76 V [95% CI: 0.72, 0.80]). Among bradycardia-indicated patients, LVEF remained stable from baseline to post-implant (59.5% [95% CI: 57.9%, 61.1%] vs. 60.1% [95% CI: 58.5%, 61.7%]). CONCLUSION: This meta-analysis including 6061 patients implanted with a Model 3830 lead for LBBAP found an average implant success rate of 92.7% and a procedural adverse event rate of 2.5% with stable electrical parameters and LVEF post-implant.

Atrioventricular optimization improves cardiac resynchronization response in patients with long interventricular electrical delays: A pooled analysis of the SMART-AV and SMART-CRT trials.

BACKGROUND: The utility of atrioventricular (AV) optimization (AVO) algorithms remains in question. A substudy of the SMART-AV trial found that patients with prolonged interventricular delays ≥70 ms were more likely to benefit from cardiac resynchronization therapy (CRT) with AVO. The SMART-CRT trial evaluated AVO on the basis of these results, but the study was underpowered. OBJECTIVE: To increase statistical power, data from SMART-AV patients meeting the inclusion criterion of interventricular delay ≥70 ms were pooled with data from SMART-CRT to reassess AVO. METHODS: SMART-CRT and SMART-AV were prospective, randomized, multicenter clinical trials. Patients in both studies were randomized to be programmed with an AVO algorithm (SmartDelay) or fixed AV delay (120 ms). Paired echocardiograms obtained at baseline and 6 months were compared, with CRT response defined as ≥15% reduction in left ventricular end-systolic volume. RESULTS: A total of 451 complete patient data sets were pooled and analyzed. The baseline demographics between studies did not differ statistically in terms of age, sex, left ventricular ejection fraction, or left ventricular end-systolic volume. The AVO group had a greater proportion of CRT responders (SmartDelay, 73.9%; fixed, 63.1%; P = .014) and greater changes in measures of reverse remodeling. SmartDelay patients with a recommended sensed AV delay outside the nominal range (100-120 ms) had 2.3 greater odds of CRT response than fixed AV delay patients. CONCLUSION: Greater CRT response and measures of reverse remodeling were observed in patients with SmartDelay enabled vs a fixed AV delay. This study supports the use of SmartDelay in patients with a CRT indication and interventricular delay ≥70 ms. GOV REGISTRATION: NCT00677014 and NCT03089281.

Outcomes with guideline-directed medical therapy and cardiac implantable electronic device therapies for patients with heart failure with reduced ejection fraction.

Background: Limited real-world evidence exists for outcomes with contemporary guideline-directed medical therapy (GDMT) or GDMT with implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) therapy for patients with heart failure with reduced ejection fraction (HFrEF) and left ventricular ejection fraction (LVEF) ≤35%. Objective: The present study aimed to assess survival associated with GDMT or GDMT with ICD/CRT-D therapy. Methods: This retrospective observational study included real-world de-identified data from January 1, 2016, to December 19, 2023, from 24 U.S. institutions per participating institutional agreements (egnite Database; egnite, Inc.). Patients with a diagnosis of HFrEF and an echocardiographic study documenting LVEF ≤35% were included for analysis. Results: Of 43,591 patients with eligible index event of LVEF ≤35%, prescription history through ≥1 year preindex, and no ICD/CRT-D therapy preindex, mean ± standard deviation age at index was 71.2 ± 13.2 years; 14,805 (34.0%) patients were female. At 24 months, an estimated 99.1% (95% confidence interval [CI] 99.0%-99.2%), 89.9% (95% CI 89.7%-90.1%), 54.8% (95% CI 54.4%-55.2%), and 17.2% (95% CI 16.9%-17.5%), had ≥1, 2, 3, or all 4 GDMT classes prescribed, respectively; an estimated 15.7% (95% CI 15.3%-16.1%) had device placement. Of those without a device, by 24 months, an estimated 45.1% (95% CI 44.4%-45.7%) had a documented LVEF >35%. Counts of GDMT classes prescribed as well as ICD/CRT-D device therapy were associated with lower mortality risk in this population, even after adjustment for patient age, sex, and comorbidities. Conclusion: Both GDMT classes prescribed and device therapy were independently associated with lower mortality risk, even in the presence of more GDMT options for this more contemporary population.

One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Comparisons of long-term clinical outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricular pacing for cardiac resynchronization therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. OBJECTIVE: This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). METHODS: Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. RESULTS: A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08-0.57]; P = .002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08-0.63]; P = .004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38-7.39]; P = .007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07-1.52], P = .155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P < .001) than BiVP or LVSP. CONCLUSION: LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk.

Stepping back for good reasons: a reappraisal of the DF-1 connector for defibrillator leads.

The DF-4 defibrillator standard has been rapidly adopted due to its convenience at implantation. There are however trade-offs compared to the traditional DF-1 standard that are underappreciated. This viewpoint outlines the advantages and limitations of current defibrillator lead standards that should be kept in mind, as they impact the options that are available to deal with issues that may arise.

Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

Sex-Specific Outcomes of LBBAP Versus Biventricular Pacing: Results From I-CLAS.

BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) has been associated with greater clinical improvement in women than men. Recently, left bundle branch area pacing (LBBAP) has been shown to be an alternative form of CRT. OBJECTIVES: The purpose of this study was to investigate sex-specific outcomes for death and heart failure events in a large, international, multicenter, cohort of patients undergoing CRT with BVP or LBBAP. METHODS: In this international study of 1,778 patients (575 female and 1203 male), sex-specific survival analysis was performed to compare the effect of LBBAP-CRT relative to BVP-CRT on the combined endpoint of death or heart failure hospitalization (HFH), and secondary endpoints of HFH only, and death alone. RESULTS: Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block (LBBB) and less likely to have hypertension, diabetes, or coronary artery disease than were male patients. Overall, female patients had a better result with LBBAP compared with BVP than did male patients, with a significant 36% reduction in death or HFH (HR: 0.64; 95% CI: 0.43 to 0.97; P = 0.03) and a significant 60% reduction in HFH alone (HR: 0.4; 95% CI: 0.24 to 0.69, P < 0.01). Women had a greater reduction in death or HFH among those with nonischemic cardiomyopathy (HR: 0.45 95% CI: 0.26 to 0.79; P < 0.01) and LBBB (HR: 0.49; 95% CI: 0.27 to 0.87; P < 0.01). Sex-specific echocardiographic outcomes were better in women than in men. CONCLUSIONS: Women obtained significantly greater reductions in the combined endpoint of death or HFH (primarily driven by reduction in HFH) with LBBAP compared with BVP among patients requiring CRT than did men.

Institutional experience report on the target contouring workflow in the radiotherapy department for stereotactic arrhythmia radioablation delivered on conventional linear accelerators.

PURPOSE: In stereotactic arrhythmia radioablation (STAR), the target is defined using multiple imaging studies and a multidisciplinary team consisting of electrophysiologist, cardiologist, cardiac radiologist, and radiation oncologist collaborate to identify the target and delineate it on the imaging studies of interest. This report describes the workflow employed in our radiotherapy department to transfer the target identified based on electrophysiology and cardiology imaging to the treatment planning image set. METHODS: The radiotherapy team was presented with an initial target in cardiac axes orientation, contoured on a wideband late gadolinium-enhanced (WB-LGE) cardiac magnetic resonance (CMR) study, which was subsequently transferred to the computed tomography (CT) scan used for treatment planning-i.e., the average intensity projection (AIP) image set derived from a 4D CT-via an axial CMR image set, using rigid image registration focused on the target area. The cardiac and the respiratory motion of the target were resolved using ciné-CMR and 4D CT imaging studies, respectively. RESULTS: The workflow was carried out for 6 patients and resulted in an internal target defined in standard anatomical orientation that encompassed the cardiac and the respiratory motion of the initial target. CONCLUSION: An image registration-based workflow was implemented to render the STAR target on the planning image set in a consistent manner, using commercial software traditionally available for radiation therapy.

Conduction system pacing: overview, definitions, and nomenclature.

Pacing from the right ventricle is associated with an increased risk of development of congestive heart failure, increases in total and cardiac mortality, and a worsened quality of life. Conduction system pacing has become increasingly realized as an alternative to right ventricular apical pacing. Conduction system pacing from the His bundle and left bundle branch area has been shown to provide physiologic activation of the ventricle and may be an alternative to coronary sinus pacing. Conduction system pacing has been studied as an alternative for both bradycardia pacing and for heart failure pacing. In this review, we summarize the clinical results of conduction system pacing under a variety of different clinical settings. The anatomic targets of conduction system pacing are illustrated, and electrocardiographic correlates of pacing from different sites in the conduction system are defined. Ultimately, clinical trials comparing conduction system pacing with standard right ventricular apical pacing and cardiac resynchronization therapy pacing will help define its benefit and risks compared with existing techniques.

Left ventricular remodeling in premature ventricular contraction-induced cardiomyopathy: Effect of coupling intervals and atrioventricular dissociation.

Background: Left ventricular dyssynchrony (LVD) and postextrasystolic potentiation (PESP) associated with premature ventricular contractions (PVCs) may play a role in the development of premature ventricular contraction-induced cardiomyopathy (PVC-CM). Long-coupled (LC) PVCs have a greater LVD than short-coupled (SC) PVCs, whereas SC-PVCs have a stronger PESP than LC-PVCs. Objective: The purpose of this study was to compare SC-PVCs and LC-PVCs to evaluate the roles of LVD, PESP, and atrioventricular dissociation (AVD) in the development of PVC-CM. Methods: Thirty-six canines underwent pacemaker implantation to induce bigeminal right ventricular apical epicardial PVCs (50% burden) for 12 weeks. Telemetry assessed PVC burden and AVD. Animals were grouped as SC-PVC (coupling interval [CI] 200-220ms), LC-PVC (CI 330 ms), or sham (control). Echocardiographic changes, AVD, and hemodynamics were monitored for 12 weeks. Results: PVC burden was similar between SC-PVC and LC-PVC groups but was statistically higher in the SC-PVC group (50% vs 47.5%; P = .028). After 12 weeks, left ventricular ejection fraction (LVEF) significantly decreased in both SC-PVC and LC-PVC groups (47.1% ± 1.4% and 45.5% ± 2%, respectively) compared to sham group (61% ± 1.6%; P <.001). Overall AVD was similar between SC-PVC and LC-PVC groups, and there was no significant correlation between AVD and reduction in LVEF at 12 weeks (r = 0.09, P = .5; and r = 0.06, P = .8, respectively). Additionally, both SC-PVC and LC-PVC groups experienced substantial declines in max and min dP/dt after 12 weeks compared to baseline. Conclusion: Neither PVC CI nor AVD played an independent role in the development or severity of PVC-CM. LVD and PESP make equal relative contributions to the development of PVC-CM.

The evolving state of cardiac resynchronization therapy and conduction system pacing: 25 years of research at EP Europace journal.

Cardiac resynchronization therapy (CRT) was proposed in the 1990s as a new therapy for patients with heart failure and wide QRS with depressed left ventricular ejection fraction despite optimal medical treatment. This review is aimed first to describe the rationale and the physiologic effects of CRT. The journey of the landmark randomized trials leading to the adoption of CRT in the guidelines since 2005 is also reported showing the high level of evidence for CRT. Different alternative pacing modalities of CRT to conventional left ventricular pacing through the coronary sinus have been proposed to increase the response rate to CRT such as multisite pacing and endocardial pacing. A new emerging alternative technique to conventional biventricular pacing, conduction system pacing (CSP), is a promising therapy. The different modalities of CSP are described (Hirs pacing and left bundle branch area pacing). This new technique has to be evaluated in clinical randomized trials before implementation in the guidelines with a high level of evidence.