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.

Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Candidates for Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well established therapy in patients with reduced left ventricular ejection fraction (LVEF), heart failure, and wide QRS or expected frequent ventricular pacing. Left bundle branch area pacing (LBBAP) has recently been shown to be a safe alternative to BVP. OBJECTIVES: The aim of this study was to compare the clinical outcomes between BVP and LBBAP among patients undergoing CRT. METHODS: This observational study included patients with LVEF ≤35% who underwent BVP or LBBAP for the first time for Class I or II indications for CRT from January 2018 to June 2022 at 15 international centers. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included endpoints of death, HFH, and echocardiographic changes. RESULTS: A total of 1,778 patients met inclusion criteria: 981 BVP, 797 LBBAP. The mean age was 69 ± 12 years, 32% were female, 48% had coronary artery disease, and mean LVEF was 27% ± 6%. Paced QRS duration in LBBAP was significantly narrower than baseline (128 ± 19 ms vs 161 ± 28 ms; P < 0.001) and significantly narrower compared to BVP (144 ± 23 ms; P < 0.001). Following CRT, LVEF improved from 27% ± 6% to 41% ± 13% (P < 0.001) with LBBAP compared with an increase from 27% ± 7% to 37% ± 12% (P < 0.001) with BVP, with significantly greater change from baseline with LBBAP (13% ± 12% vs 10% ± 12%; P < 0.001). On multivariable regression analysis, the primary outcome was significantly reduced with LBBAP compared with BVP (20.8% vs 28%; HR: 1.495; 95% CI: 1.213-1.842; P < 0.001). CONCLUSIONS: LBBAP improved clinical outcomes compared with BVP in patients with CRT indications and may be a reasonable alternative to BVP.

Evaluation of lead-based echodensities on transesophageal echocardiogram in patients with cardiac implantable electronic devices.

INTRODUCTION: Transesophageal echocardiography (TEE) is recommended to rule out endocarditis in patients with cardiac implantable electronic devices (CIED). A lead-based echodensity (LBE), however, is often found on TEE in patients with a CIED and may not represent an infection. We sought to evaluate the predictors, characteristics, and clinical significance of LBEs seen on TEE in patients with a CIED. METHODS: Patients with a CIED were retrospectively identified from a database using International Classification of Diseases (ICD)-9/ICD-10 codes and were cross-matched with Current Procedural Terminology codes for a TEE. Clinical and follow-up data were collected. A blinded echo board-certified cardiologist reviewed all TEEs. RESULTS: Out of the 231 patients in the cohort, 191 had TEE performed for a noninfection-related indication while 40 TEEs were part of an endocarditis workup. A total of 50 LBEs were identified, and a majority were in the noninfection cohort. Systemic anticoagulant use in the noninfection cohort was associated with a decreased odds of having LBE on TEE (odds ratio [OR] of 0.23 [95% confidence interval [CI]: 0.06-0.60, p = .003]). Lead dwell time in the noninfection cohort was associated with an increased odds of having LBE on TEE (OR 1.21 (95% CI: 1.04-1.39, p = .009]). CONCLUSION: In our cohort of patients who had TEE for noninfection indications we found that systemic anticoagulant use is associated with fewer LBEs on TEEs, suggesting possible thrombin fibrin composition of LBE.

New-onset atrial fibrillation incidence and associated outcomes in the medical intensive care unit.

BACKGROUND: In patients with critical medical illness, data regarding new-onset atrial fibrillation (NOAF) is relatively sparse. This study examines the incidence, associated risk factors, and associated outcomes of NOAF in patients in the medical intensive care unit (MICU). METHODS: This single-center retrospective observational cohort study included 2234 patients with MICU stays in 2018. An automated extraction process using ICD-10 codes, validated by a 196-patient manual chart review, was used for data collection. Demographics, medications, and risk factors were collected. Multiple risk scores were calculated for each patient, and AF recurrence was also manually extracted. Length of stay, mortality, and new stroke were primary recorded outcomes. RESULTS: Two hundred and forty one patients of the 2234 patient cohort (11.4%) developed NOAF during their MICU stay. NOAF was associated with greater length of stay in the MICU (5.84 vs. 3.52 days, p < .001) and in the hospital (15.7 vs. 10.9 days, p < .001). Patients with NOAF had greater odds of hospital mortality (odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.34-2.71, p < .001) and 1-year mortality (OR = 1.37, 95% CI 1.02-1.82, p = .03). CHARGE-AF scores performed best in predicting NOAF (area under the curve (AUC) 0.691, p < .001). CONCLUSIONS: The incidence of NOAF in this MICU cohort was 11.4%, and NOAF was associated with a significant increase in hospital LOS and mortality. Furthermore, the CHARGE-AF score performed best in predicting NOAF.

Serum Cotinine and Silent Myocardial Infarction in Individuals Free from Cardiovascular Disease.

Serum cotinine is a sensitive and specific marker of tobacco exposure, including second-hand smoke exposure. We sought to explore the association of tobacco exposure determined by serum cotinine with electrocardiographic silent myocardial infarction (SMI). A total of 7,006 participants (59.0 ± 13.3 years; 52.6% women, 49.7% non-Hispanic whites) without cardiovascular disease from the Third National Health and Nutrition Examination Survey (NHANES III) were included in this analysis. SMI was defined as electrocardiographic evidence of MI in the absence of a history of MI. Multivariable logistic regression analysis was used to examine the association between SMI and serum cotinine tertiles. SMI was detected in 114 (1.63%) of the participants. The prevalence of SMI was higher among those with higher levels of serum cotinine (SMI prevalence was 1.25%, 1.49%, and 2.14% across serum cotinine lower [0.03 to 0.12 ng/ml], middle [0.12 to 1.39 ng/ml], and higher [1.40 to 1890 ng/ml] tertiles, respectively). In a model adjusted for potential confounders, participants within the highest serum cotinine tertile had significantly greater odds of SMI (odds ratio [95% confidence interval]: 2.51 [1.55 to 4.08]) compared with those with serum cotinine levels in the first tertile. Each 10 ng/ml increase in serum cotinine levels was associated with a 2% (p <0.0001) increase in the prevalence of SMI. This association was stronger in white than nonwhite participants (interaction p value = 0.05). In conclusion, elevated serum cotinine levels are associated with SMI. These findings further highlight the risk associated with passive and active smoking on cardiovascular health and underscore the potential utility of serum cotinine in identifying those at risk.

Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains.

We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.