Current role of Conduction System Pacing in Patients Requiring Permanent Pacing.

His bundle pacing (HBP) and left bundle branch pacing (LBBP) are novel methods of pacing directly pacing the cardiac conduction system. HBP while developed more than two decades ago, only recently moved into the clinical mainstream. In contrast to conventional cardiac pacing, conduction system pacing including HBP and LBBP utilizes the native electrical system of the heart to rapidly disseminate the electrical impulse and generate a more synchronous ventricular contraction. Widespread adoption of conduction system pacing has resulted in a wealth of observational data, registries, and some early randomized controlled clinical trials. While much remains to be learned about conduction system pacing and its role in electrophysiology, data available thus far is very promising. In this review of conduction system pacing, the authors review the emergence of conduction system pacing and its contemporary role in patients requiring permanent cardiac pacing.

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.

BACKGROUND: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT). METHODS: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies. RESULTS: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A, SCN10A, and TTN/CCDC141. Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals. CONCLUSIONS: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.

His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) using His bundle pacing (HBP) or left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). OBJECTIVES: The aim of the study was to compare the feasibility and clinical efficacy of HOT-CRT (His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy) with BVP in patients with heart failure, reduced ejection fraction, and indication for CRT. METHODS: This was a prospective, randomized, controlled trial of HOT-CRT and BVP in patients with LVEF <50% and indications for CRT. If HPCSP resulted in incomplete electrical resynchronization, a coronary sinus (CS) lead was added. The primary outcome was the change in left ventricular ejection fraction (LVEF) at 6 months. The primary safety endpoint was freedom from major complications. RESULTS: A total of 100 patients (female 31%, aged 70 ± 12 years, LVEF 31.5% ± 9.0%) were randomized. HOT-CRT was successful in 48 of 50 (96%) and BVP-CRT in 41 of 50 (82%) patients (P = 0.03). QRS duration significantly decreased from 164 ± 26 ms to 137 ± 20 ms with HOT-CRT and 166 ± 28 ms to 141 ± 19 ms with BVP. Fluoroscopy results (18.8 ± 12.4 min vs 23.8 ± 12.4 min, P = 0.05) and procedure duration (119 ± 42 min vs 114 ± 36 min, P = 0.5) were similar. The primary outcome of change in LVEF at 6 months was greater in HOT-CRT than in BVP (12.4% ± 7.3% vs 8.0% ± 10.1%, P = 0.02). The primary safety endpoint was similar (98% vs 94%, P = 0.62). Echocardiographic response of improvement in LVEF >5% occurred in 80% vs 61% (P = 0.06). Complications occurred in 3 (6%) in HOT-CRT vs 10 (20%) in BVP (P = 0.03). CONCLUSIONS: HPCSP-guided CRT resulted in greater change in LVEF compared with BVP. Randomized clinical trials with long-term follow-up are necessary. (His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy [HOT-CRT]; NCT04561778).

Atrial Fibrillation Ablation in a Patient With SV ASD and PAPVR Preceding Transcatheter Septal Closure.

Atrial fibrillation (AF) is common in adults with unrepaired atrial septal defects (ASDs). Sinus venosus (SV) ASDs associated with partial anomalous pulmonary venous return (PAPVR) are traditionally managed surgically. We report the first AF catheter ablation in a patient with SV ASD and PAPVR preceding transcatheter ASD repair with a covered stent. (Level of Difficulty: Advanced.).

Left bundle branch area pacing in patients with heart failure and right bundle branch block: Results from International LBBAP Collaborative-Study Group.

Background: Cardiac resynchronization therapy (CRT) using biventricular pacing has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) is a novel physiologic pacing option. Objective: The aim of the study was to assess the feasibility and outcomes of LBBAP in HF patients with RBBB and reduced left ventricular systolic function, and indication for CRT or ventricular pacing. Methods: LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) <50%, RBBB, HF, and indications for CRT or ventricular pacing. Procedural, pacing, and electrocardiographic parameters; clinical response (no HF hospitalization and improvement in NYHA class); and echocardiographic response (≥5% increase in ejection fraction) to LBBAP were assessed. Results: LBBAP was attempted in 121 patients and successful in 107 (88%). Patient characteristics included age 74 ± 12 years, female 25%, ischemic cardiomyopathy 49%, and ejection fraction 35% ± 9%. QRS axis at baseline was normal in 24%, left axis 63%, right axis 13%. LBBAP threshold and R-wave amplitudes were 0.8 ± 0.3 V @ 0.5 ms and 10 ± 9 mV at implant and remained stable during mean follow-up of 13 ± 8 months. LBBAP resulted in narrowing of QRS duration (156 ± 20 ms to 150 ± 24 ms (P = .01) with R-wave peak times in V6 of 85 ± 16 ms. LVEF improved from 35% ± 9% to 43% ± 12% (P < .01). Clinical and echocardiographic response was observed in 60% and 61% of patients, respectively. Female sex and reduction in QRS duration with LBBAP were predictive of echocardiographic response and super-response. Conclusion: LBBAP is a feasible alternative to deliver CRT or physiologic ventricular pacing in patients with RBBB, HF, and LV dysfunction.

C-reactive Protein Elevation Is Associated With QTc Interval Prolongation in Patients Hospitalized With COVID-19.

Background: The relationship between inflammation and corrected QT (QTc) interval prolongation is currently not well defined in patients with COVID-19. Objective: This study aimed to assess the effect of marked interval changes in the inflammatory marker C-reactive protein (CRP) on QTc interval in patients hospitalized with COVID-19. Methods: In this retrospective cohort study of hospitalized adult patients admitted with COVID-19 infection, we identified 85 patients who had markedly elevated CRP levels and serial measurements of an ECG and CRP during the same admission. We compared mean QTc interval duration, and other clinical and ECG characteristics between times when CRP values were high and low. We performed mixed-effects linear regression analysis to identify associations between CRP levels and QTc interval in univariable and adjusted models. Results: Mean age was 58 ± 16 years, of which 39% were women, 41% were Black, and 25% were White. On average, the QTc interval calculated via the Bazett formula was 15 ms higher when the CRP values were "high" vs. "low" [447 ms (IQR 427-472 ms) and 432 ms (IQR 412-452 ms), respectively]. A 100 mg/L increase in CRP was associated with a 1.5 ms increase in QTc interval [ß coefficient 0.15, 95% CI (0.06-0.24). In a fully adjusted model for sociodemographic, ECG, and clinical factors, the association remained significant (ß coefficient 0.14, 95% CI 0.05-0.23). Conclusion: An interval QTc interval prolongation is observed with a marked elevation in CRP levels in patients with COVID-19.

His-Purkinje Conduction System Pacing in Atrioventricular Block: New Insights Into Site of Conduction Block.

OBJECTIVES: This study aims to assess the safety and feasibility of achieving His-Purkinje conduction system pacing (HPCSP) in consecutive patients with atrioventricular block (AVB) and to describe the site of conduction block in patients with infranodal AVB. BACKGROUND: HPCSP has evolved as the preferred form of physiologic pacing. Left bundle branch area pacing (LBBAP) has emerged as an effective alternative to His bundle pacing (HBP). METHODS: Consecutive patients with AVB referred for pacemaker implantation were included in the study. HBP or LBBAP was attempted in all patients. Site of conduction block was identified as nodal or infranodal (intra-Hisian or infra-Hisian) AVB. RESULTS: HPCSP was attempted in 333 consecutive patients with AVB and was successful in 322 (97%) patients. HBP was achieved in 140 patients, LBBAP in 179 patients, and both in 3 patients. Site of conduction block was nodal in 55% and infranodal in 45% (intra-Hisian 89%; infra-Hisian 4%; indeterminate 7%). QRS duration at baseline was 111 ± 27 versus 129 ± 31 (P < 0.001) compared to 126 ± 24 vs 125 ± 21 milliseconds (P = 0.75) during HBP and LBBAP, respectively. HBP thresholds at implant were higher compared to LBBAP (1.2 ± 0.7 V at 0.9 milliseconds vs 0.6 ± 0.3 V at 0.5 milliseconds; P < 0.001) but remained stable during follow-up. Lead revision was required in 3% and 2% of patients with HBP and LBBAP, respectively. CONCLUSIONS: HPCSP pacing was successfully performed in 97% of unselected patients with AVB irrespective of the site of conduction block. True infra-Hisian block (distal His-Purkinje conduction disease) is rare. HBP and LBBAP were complementary in achieving stable and low capture thresholds.

Acquired Long QT and Ventricular Arrhythmias in the Setting of Acute Inflammation: A Case Series.

We report a case series of 4 patients with transient marked QTc prolongation and ventricular arrhythmias in the setting of inflammation with very high ferritin levels. Three patients were positive for coronavirus disease-2019. In the setting of an acute rise in inflammatory markers, electrocardiography screening for QTc prolongation is warranted. (Level of Difficulty: Beginner.).

Clinical Findings and Diagnostic Yield of Arrhythmogenic Cardiomyopathy Through Genomic Screening of Pathogenic or Likely Pathogenic Desmosome Gene Variants.

BACKGROUND: Genomic screening holds great promise for presymptomatic identification of hidden disease, and prevention of dramatic events, including sudden cardiac death associated with arrhythmogenic cardiomyopathy (ACM). Herein, we present findings from clinical follow-up of carriers of ACM-associated pathogenic/likely pathogenic desmosome variants ascertained through genomic screening. METHODS: Of 64 548 eligible participants in Geisinger MyCode Genomic Screening and Counseling program (2015-present), 92 individuals (0.14%) identified with pathogenic/likely pathogenic desmosome variants by clinical laboratory testing were referred for evaluation. We reviewed preresult medical history, patient-reported family history, and diagnostic testing results to assess both arrhythmogenic right ventricular cardiomyopathy and left-dominant ACM. RESULTS: One carrier had a prior diagnosis of dilated cardiomyopathy with arrhythmia; no other related diagnoses or diagnostic family history criteria were reported. Fifty-nine carriers (64%) had diagnostic testing in follow-up. Excluding the variant, 21/59 carriers satisfied at least one arrhythmogenic right ventricular cardiomyopathy task force criterion, 11 (52%) of whom harbored DSP variants, but only 5 exhibited multiple criteria. Six (10%) carriers demonstrated evidence of left-dominant ACM, including high rates of atypical late gadolinium enhancement by magnetic resonance imaging and nonsustained ventricular tachycardia. Two individuals received new cardiomyopathy diagnoses and received defibrillators for primary prevention. CONCLUSIONS: Genomic screening for pathogenic/likely pathogenic variants in desmosome genes can uncover both left- and right-dominant ACM. Findings of overt cardiomyopathy were limited but were most common in DSP-variant carriers and notably absent in PKP2-variant carriers. Consideration of the pathogenic/likely pathogenic variant as a major criterion for diagnosis is inappropriate in the setting of genomic screening.

Left Bundle Branch Area Pacing for Cardiac Resynchronization Therapy: Results From the International LBBAP Collaborative Study Group.

OBJECTIVES: The aim of this study was to assess the feasibility and outcomes of left bundle branch area pacing (LBBAP) in patients eligible for cardiac resynchronization therapy (CRT) in an international, multicenter, collaborative study. BACKGROUND: CRT using biventricular pacing is effective in patients with heart failure and left bundle branch block (LBBB). LBBAP has been reported as an alternative option for CRT. METHODS: LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) <50% and indications for CRT or pacing. Procedural outcomes, left bundle branch capture, New York Heart Association functional class, heart failure hospitalization, echocardiographic data, and lead complications were recorded. Clinical (no heart failure hospitalization and improvement in New York Heart Association functional class) and echocardiographic responses (≥5% improvement in LVEF) were assessed. RESULTS: LBBAP was attempted in 325 patients, and CRT was successfully achieved in 277 (85%) (mean age 71 ± 12 years, 35% women, ischemic cardiomyopathy in 44%). QRS configuration at baseline was LBBB in 39% and non-LBBB in 46%. Procedure and fluoroscopy duration were 105 ± 54 and 19 ± 15 min, respectively. LBBAP threshold and R-wave amplitudes were 0.6 ± 0.3 V at 0.5 ms and 10.6 ± 6 mV at implantation and remained stable during mean follow-up of 6 ± 5 months. LBBAP resulted in significant QRS narrowing from 152 ± 32 to 137 ± 22 ms (p < 0.01). LVEF improved from 33 ± 10% to 44 ± 11% (p < 0.01). Clinical and echocardiographic responses were observed in 72% and 73% of patients, respectively. Baseline LBBB (odds ratio: 3.96; 95% confidence interval: 1.64 to 9.26; p < 0.01) and left ventricular end-diastolic diameter (odds ratio: 0.62; 95% confidence interval: 0.49 to 0.79; p < 0.01) were independent predictors of echocardiographic response. CONCLUSIONS: LBBAP is feasible and safe and provides an alternative option for CRT. LBBAP provides remarkably low and stable pacing thresholds and was associated with improved clinical and echocardiographic outcomes.

Prevalence and Predictors of Obstructive Coronary Artery Disease in Nonlow-risk Acute Chest Pain Patients Who Rule Out for Myocardial Infarction in the High-sensitivity Troponin Era.

OBJECTIVES: The best management approach for chest pain patients who rule out for myocardial infarction (MI) in the high-sensitivity troponin (hsTn) era remains elusive. Patients, especially those with nonlow clinical risk scores, are often referred for inpatient ischemic testing to uncover obstructive coronary artery disease (CAD). Whether the prevalence of obstructive CAD in this cohort is high enough to justify routine testing is not known. METHODS: We conducted a retrospective cohort analysis of 1517 emergency department chest pain patients who ruled out for MI by virtue of a stable high-sensitivity troponin T (hsTnT) levels (defined as <5 ng/L intermeasurements increase) and were admitted for inpatient testing. RESULTS: Abnormal ischemia evaluation (including 5.9% with evidence of fixed wall motion or perfusion defects) was 11.9%. Of those undergoing invasive angiography (n = 292), significant coronary stenoses (≥70% or unstable lesions) and multivessel CAD occurred in 16.8% and 5.5%, respectively. In a multivariate logistic regression model, known CAD, prior MI, chest pain character, mildly elevated hsTnT, and left ventricular ejection fraction <40% were predictive of an abnormal ischemia evaluation result, whereas electrocardiography findings and the modified History, EKG, Age, Risk factors, and troponin (HEART) score were not. Of note, 30-day adverse cardiac events were strikingly low at 0.4% with no deaths despite an overwhelming majority (>90%) of patients scoring intermediate or high on the modified HEART score. CONCLUSIONS: A considerable percentage of acute chest pain patients who rule out for MI by hsTn had evidence of obstructive CAD, and the modified HEART score was not predictive of an abnormal ischemia evaluation.

His bundle pacing capture threshold stability during long-term follow-up and correlation with lead slack.

AIMS: His bundle pacing (HBP) is the most physiologic form of pacing. Long-term HBP capture threshold stability and its relation to lead characteristics at the time of implantation have not been adequately described. The aim of this study was to characterize HB capture threshold in follow-up and to identify potential lead characteristics predictive of lead capture instability. METHODS AND RESULTS: Consecutive patients with successful HBP for bradycardia indications were identified from the Geisinger HBP registry. His bundle capture thresholds, baseline comorbidities, and radiographic lead slack characteristics were analysed. An increase in HB capture threshold ≥1 V above implant values at any time during follow-up was tracked. Forty-four of the 294 studied (15%) experienced HB capture threshold increase by ≥ 1 V. Threshold increase was seen early (41% by 8 weeks, 66% by 1 year). Eighteen (6%) patients required lead revision in follow-up. Abnormal slack shape was associated with a trend toward capture threshold increase [hazard ratio (HR) 2.07; 95% confidence interval (CI) 0.9-4.6; P = 0.08]. Non-perpendicular angle of lead insertion on radiography was associated with the capture threshold increase (HR 2.81, 95% CI 1.4-5.8; P < 0.01). CONCLUSION: His bundle capture threshold remains stable in the majority (85%) of patients. Implant characteristics may predict the threshold rise. Further evaluation of the aetiology of threshold increase and design changes in lead and delivery systems may lead to chronically stable capture thresholds.

Development of New-Onset or Progressive Atrial Fibrillation in Patients With Permanent HIS Bundle Pacing Versus Right Ventricular Pacing: Results From the RUSH HBP Registry.

Background Conventional right ventricular pacing (RVP) has been associated with an increased incidence of atrial fibrillation (AF). We sought to compare the occurrence of new-onset AF and assessed AF disease progression during long-term follow-up between His bundle pacing (HBP) and RVP. Methods and Results We included patients undergoing initial dual-chamber pacemaker implants at Rush University Medical Center between January 1, 2016, and June 30, 2019. A total of 360 patients were evaluated, and 225 patients (HBP, n=105; RVP, n=120) were included in the study. Among the 148 patients (HBP, n=72; RVP, n=76) with no history of AF, HBP demonstrated a lower risk of new-onset AF (adjusted hazard ratio [HR], 0.53; 95% CI, 0.28-0.99; P=0.046) compared with traditional RVP. This benefit was observed with His or RVP burden exceeding 20% (HR, 0.29; 95% CI, 0.13-0.64; P=0.002), ≥40% (HR, 0.31; P=0.007), ≥60% (HR, 0.35; P=0.015), and ≥80% (HR, 0.40; P=0.038). There was no difference with His or RV pacing burden <20% (HR, 0.613; 95% CI, 0.213-1.864; P=0.404). In patients with a prior history of AF, there was no difference in AF progression (P=0.715); however, in a subgroup of patients with a pacing burden ≥40%, HBP demonstrated a trend toward a lower risk of AF progression (HR, 0.19; 95% CI, 0.03-1.16; P=0.072). Conclusions HBP demonstrated a lower risk of new-onset AF compared with RVP, which was primarily observed at a higher pacing burden.

Prediction of mortality from 12-lead electrocardiogram voltage data using a deep neural network.

The electrocardiogram (ECG) is a widely used medical test, consisting of voltage versus time traces collected from surface recordings over the heart1. Here we hypothesized that a deep neural network (DNN) can predict an important future clinical event, 1-year all-cause mortality, from ECG voltage-time traces. By using ECGs collected over a 34-year period in a large regional health system, we trained a DNN with 1,169,662 12-lead resting ECGs obtained from 253,397 patients, in which 99,371 events occurred. The model achieved an area under the curve (AUC) of 0.88 on a held-out test set of 168,914 patients, in which 14,207 events occurred. Even within the large subset of patients (n = 45,285) with ECGs interpreted as 'normal' by a physician, the performance of the model in predicting 1-year mortality remained high (AUC = 0.85). A blinded survey of cardiologists demonstrated that many of the discriminating features of these normal ECGs were not apparent to expert reviewers. Finally, a Cox proportional-hazard model revealed a hazard ratio of 9.5 (P < 0.005) for the two predicted groups (dead versus alive 1 year after ECG) over a 25-year follow-up period. These results show that deep learning can add substantial prognostic information to the interpretation of 12-lead resting ECGs, even in cases that are interpreted as normal by physicians.

Percutaneous Extraction of an Embolized IVC Filter Strut Embedded in the Right Ventricle.

The incidence of IVC filter fracture is high with risk for embolization and may require open surgery. We present a minimally invasive approach of complex transcatheter extraction of an embolized and embedded IVC filter strut from the right ventricle. (Level of Difficulty: Intermediate.).

Prevalence and Electronic Health Record-Based Phenotype of Loss-of-Function Genetic Variants in Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Genes.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with variants in desmosome genes. Secondary findings of pathogenic/likely pathogenic variants, primarily loss-of-function (LOF) variants, are recommended for clinical reporting; however, their prevalence and associated phenotype in a general clinical population are not fully characterized. METHODS: From whole-exome sequencing of 61 019 individuals in the DiscovEHR cohort, we screened for putative loss-of-function variants in PKP2, DSC2, DSG2, and DSP. We evaluated measures from prior clinical ECG and echocardiograms, manually over-read to evaluate ARVC diagnostic criteria, and performed a PheWAS (phenome-wide association study). Finally, we estimated expected penetrance using Bayesian inference. RESULTS: One hundred forty individuals (0.23%; 59±18 years old at last encounter; 33% male) had an ARVC variant (G+). None had an existing diagnosis of ARVC in the electronic health record, nor significant differences in prior ECG or echocardiogram findings compared with matched controls without variants. Several G+ individuals satisfied major repolarization (n=4) and ventricular function (n=5) criteria, but this prevalence matched controls. PheWAS showed no significant associations of other heart disease diagnoses. Combining our best genetic and disease prevalence estimates yields an estimated penetrance of 6.0%. CONCLUSIONS: The prevalence of ARVC loss-of-function variants is ≈1:435 in a general clinical population of predominantly European descent, but with limited electronic health record-based evidence of phenotypic association in our population, consistent with a low penetrance estimate. Prospective deep phenotyping and longitudinal follow-up of a large sequenced cohort is needed to determine the true clinical relevance of an incidentally identified ARVC loss-of-function variant.

Clinical Outcomes of Selective Versus Nonselective His Bundle Pacing.

OBJECTIVES: The aim of the study was to evaluate the clinical outcomes of nonselective (NS) His bundle pacing (HBP) compared with selective (S) HBP. BACKGROUND: HBP is the most physiologic form of ventricular pacing. NS-HBP results in right ventricular septal pre-excitation due to fusion with myocardial capture in addition to His bundle capture resulting in widened QRS duration compared with S-HBP wherein there is exclusive His bundle capture and conduction. METHODS: The Geisinger and Rush University HBP registries comprise 640 patients who underwent successful HBP. Our study population included 350 consecutive patients treated with HBP for bradyarrhythmic indications who demonstrated ≥20% ventricular pacing burden 3 months post-implantation. Patients were categorized into S-HBP or NS-HBP based on QRS morphology (NS-HBP n = 232; S-HBP n = 118) at the programmed output at the 3-month follow-up. The primary analysis outcome was a combined endpoint of all-cause mortality or heart failure hospitalization. RESULTS: The NS-HBP group had a higher number of men (64% vs. 50%; p = 0.01), higher incidence of infranodal atrioventricular block (40% vs. 9%; p < 0.01), ischemic cardiomyopathy (24% vs. 14%; p = 0.03), and permanent atrial fibrillation (18% vs. 8%; p = 0.01). The primary endpoint occurred in 81 of 232 patients (35%) in the NS-HBP group compared with 23 of 118 patients (19%) in the S-HBP group (hazard ratio: 1.38; 95% confidence interval: 0.87 to 2.20; p = 0.17). Subgroup analyses of patients at greatest risk (higher pacing burden or lower left ventricular ejection fraction) revealed no incremental risk with NS-HBP. CONCLUSIONS: NS-HBP was associated with similar outcomes of death or heart failure hospitalization when compared with S-HBP. Multicenter risk-matched clinical studies are needed to confirm these findings.