Citations

Abstract Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. Results: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10−8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. Conclusions: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. Impact: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

Background: The outcomes of leadless pacemaker (LP) implantation after transvenous lead removal (TLR) of infected cardiac implantable electronic devices (CIED) are not well-established. Objective: This study sought to describe the outcomes of LP implantation following TLR of infected CIED. Method: We conducted a literature search using PubMed and Embase for a combination of term including leadless pacemaker implantation, transvenous lead extraction, transvenous lead removal , transvenous lead explant , infected cardiac implantable electronic device . The inclusion criterion was LP implantation after TLR of infected CIED. The exclusion criterion was TLR for non-infectious reason. Study end-points were procedural complications and LP infection. Result: Of 132 publications reviewed, 13 studies with a total of 253 patients (74 ± 14 years of age, 69% males) were included. Amongst, 56.8% had systemic CIED infection and 43.2% had isolated pocket infection. Staphylococcus Aureus was the most common causative organism in 33% of the reported patients. Of 253 patients included, 105 patients (41.5%) underwent concomitant LP implantation during TLR procedure, and 36 patients (14.2%) had transvenous pacing as a bridge from TLR to LP implantation. During the LP implantation, 1 patient (0.4%) had an intra-procedural complication requiring sternotomy. Post-LP implantation, 2 patients (0.8%) developed groin hematoma, 2 patients (0.8%) developed femoral arteriovenous fistula, and 1 patient (0.4%) developed pericardial effusion requiring pericardiocentesis. During a mean follow-up of 11.3 ±10.6 months, 3 patients (1.2%) developed pacemaker syndrome, 1 patient (0.4%) developed acute on chronic heart failure exacerbation, and only 1 patient (0.4%) developed LP-related infection requiring LP retrieval. Conclusion: This study suggests that LP implant is feasible and safe post-removal of infected CIED with cumulative adverse events at 4% and a reinfection rate of 0.4%.

Background: There is limited evidence regarding the impact of cardiac arrhythmias in patients with pulmonary arterial hypertension (PAH). We aim to comprehensively investigate the epidemiology and clinical outcomes of cardiac arrhythmias in patients with PAH. Methods: In a retrospective cohort study including 512 PAH patients from 2001-2021 at 3 Mayo Clinic sites, PAH patients were identified via echocardiogram, pulmonary function tests, and right heart catheterization. Demographic data at PAH diagnosis and clinical outcomes over a 10-year period were collected. The PAH patients were categorized into three groups based on arrhythmic onset: 1) patients with arrhythmia prior to PAH diagnosis, 2) patients diagnosed with arrhythmia during 10-year PAH follow-up, and 3) patients without arrhythmia during 10-year PAH follow-up. Survival outcomes were analyzed using multivariable Cox proportional hazards regression, adjusted with the REVEAL 2.0 score. Results: Among 512 PAH patients (mean age 56.1 years, 81.8% female), the prevalence of cardiac arrhythmias at PAH diagnosis was 10.5%. The cumulative incidences of new-onset arrhythmias at 1, 5, and 10 years were 6.6%, 18.4%, and 29.2%, respectively. Patients with arrhythmia diagnosed before and after PAH diagnosis showed significantly higher all-cause mortality rates with adjusted HR of 2.06 [95% CI 1.36-3.12] and 1.57 [95% CI 1.17-2.20] respectively (Figure 1). Similarly in both arrhythmic groups, there was a shorter median time to the first all-cause hospitalization (9.5 and 15.9 months vs. 21.2 months) and a higher number of all-cause hospitalizations (0.38 and 0.64 times per year vs. 0.10 times per year) compared to the non-arrhythmic group. Conclusions: Cardiac arrhythmias can develop in nearly one-third of PAH patients within 10 years of PAH diagnosis and independently contribute to increased mortality and hospitalization frequency.

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed over the past decades. However, the real-world data on the safety profile of this procedure among elderly patients is limited. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among those aged 18-64 years versus those aged ≥65 years who underwent catheter ablation of VT. Method: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non-elderly (18-64 years old) and elderly age groups (≥65 years old). We then analyzed the in-hospital procedural outcome and 30-day readmission between these groups. Results: Our study included 2075 (49.1%) non-elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Following the procedure, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days) (35.5% vs 29.3%, p<0.01), non-home discharge (13.4% vs 6.0%, p<0.01), 30-day readmission (17.0% vs 11.4%, p<0.01), and early mortality (5.5% v 2.4%, p<0.01). The median cumulative cost of hospitalization was significantly higher in the elder groups ($40,230 vs. $37,612, p ≤0.01). There was no significant difference in the procedural complications between the two groups. Through multivariable analysis, the elderly group was associated with significantly higher odds of early mortality (OR: 7.50; CI 1.86 - 30.31, p=0.01), non-home discharge (OR: 2.41; CI: 1.93 - 3.00, p<0.01) and 30-day readmissions (OR: 1.58; CI 1.32 - 1.89, p<0.01). Conclusion: Our study suggests that elderly patients have poorer in-hospital outcome in early mortality, non-home discharge and 30-day readmissions following catheter ablation for VT. There was no significant difference between elderly and non-elderly groups in the procedural complications.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.