Thomas A. Blackwell

Background: Evidence comparing intermediate‐term outcomes of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients with concomitant heart failure and chronic kidney disease remains limited. Methods: Using the TriNetX Global Collaborative Network, we conducted a retrospective study of adults with heart failure and chronic kidney disease undergoing TAVI or SAVR between January 2020 and December 2025. We excluded patients with redo procedures, history of endocarditis, prior heart transplant, ventricular assist device placement, or concomitant valve surgery. The primary outcome was all‐cause death. Secondary outcomes included acute myocardial infarction, ischemic stroke, acute kidney injury, and all‐cause hospitalization. Outcomes were assessed over 2 years of follow‐up using Cox proportional hazards models. Results: Before matching, 9575 patients underwent TAVI and 1233 underwent SAVR. Propensity score matching across 21 covariates balanced demographics, comorbidities, medications, and laboratory values, yielding 1034 matched patients in each cohort. During follow‐up, TAVI was associated with a higher mortality rate (hazard ratio [HR], 1.56 [95% CI, 1.21–2.01]) and lower risk of acute kidney injury (HR, 0.69 [95% CI, 0.60–0.80]) compared with SAVR. Risks of acute myocardial infarction (HR, 1.12 [95% CI, 0.87–1.44]), ischemic stroke (HR, 1.11 [95% CI, 0.85–1.45]), and all‐cause hospitalization (HR, 0.90 [95% CI, 0.81–1.00]) were similar. Sensitivity analyses across alternative modeling strategies yielded directionally consistent results. Conclusions: In this contemporary‐era cohort of patients with heart failure and chronic kidney disease, SAVR was associated with a lower mortality rate, whereas TAVI was associated with less acute kidney injury. These findings suggest important trade‐offs between procedural strategies in high‐risk cardiorenal populations.

Background: Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular and neurocognitive complications. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2is) have pleiotropic effects beyond glycemic control, but comparative long-term data on dementia, cardiovascular events, and mortality in older adults are limited. Methods: This retrospective cohort study used the TriNetX US Collaborative Network. Adults ≥60 years with T2DM on metformin plus either GLP-1 RAs or SGLT2is (n=56,211 per cohort after matching, 2014–2020) were propensity-score matched on demographic and clinical characteristics. Five-year outcomes included incident Alzheimer’s disease, vascular dementia, other dementia, dementia-related medication use, NSTEMI, STEMI, and all-cause mortality. Results: After propensity-score matching, GLP-1 RA use was associated with higher risks of Alzheimer’s disease (RR 1.33, 95% CI 1.18–1.48), vascular dementia (RR 1.56, 95% CI 1.39–1.76), other dementia (RR 1.33, 95% CI 1.21–1.47), dementia-related medication initiation, and all-cause mortality (RR 1.11, 95% CI 1.08–1.15) compared with SGLT2is. NSTEMI and STEMI risks did not differ significantly between groups. Conclusions: In older adults with T2DM, SGLT2is were associated with lower risks of dementia, dementia-related medication use, and all-cause mortality compared with GLP-1 RAs in propensity-score matched cohorts. These observational findings are hypothesis-generating and should be confirmed in prospective studies.

Background: Sex-related differences are well recognized in heart failure with preserved ejection fraction (HFpEF), but real-world data describing clinical outcomes by sex among patients with obesity and HFpEF treated with tirzepatide remain limited. Objectives: To compare observed hospitalization, cardiovascular, and gastrointestinal outcomes between male and female patients with obesity and HFpEF treated with tirzepatide. Design: Retrospective, propensity score-matched, within-treatment cohort study. Methods: A retrospective study was conducted using TriNetX database which included 110 healthcare organizations. Adults with obesity, HFpEF, and taking tirzepatide between June 1, 2022 and January 1, 2025 were identified. Males and females were balanced using 1:1 propensity score matching (n=1,654 per group). Primary outcome assessed included all-cause hospitalization. Secondary outcomes were all-cause mortality, HF exacerbation, major adverse cardiovascular events (MACE), incident atrial fibrillation, nausea/vomiting and diarrhea. Two prespecified falsification endpoints were used. Results: During 1-year follow-up, males had a lower hazard of all-cause hospitalization compared with females (HR 0.87, 95% CI 0.77–0.98). No significant differences were observed for all-cause mortality (HR 1.73, 95% CI 0.95–3.18), HF exacerbation (HR 1.14, 95% CI 0.90–1.44), MACE (HR 1.28, 95% CI 0.99–1.65), or incident atrial fibrillation (HR 1.21, 95% CI 0.61–2.43). Males experienced lower rates of nausea and vomiting (HR 0.50, 95% CI 0.37–0.67), while diarrhea was similar (HR 0.84, 95% CI 0.59–1.19). Falsification endpoints showed no significant associations. Conclusion: Among tirzepatide-treated patients with obesity and HFpEF, no statistically significant sex-associated differences were detected in major cardiovascular outcomes. Males had a modestly lower observed hazard of hospitalization and fewer coded nausea and vomiting events. Because this was a within-treatment observational comparison without an external comparator, these findings should not be interpreted as evidence of differential tirzepatide effectiveness by sex.

Cardiovascular disease remains the leading cause of line-of-duty mortality among firefighters. Sudden cardiac death occurs disproportionately during emergency operations, particularly fire suppression, suggesting an interaction between occupational stressors and underlying cardiovascular vulnerability. This narrative review integrates epidemiologic, mechanistic, and clinical data from observational studies, systematic reviews, and contemporary cardiovascular guidelines. A structured literature search of PubMed and Google Scholar identified studies addressing cardiovascular disease, sudden cardiac death, occupational stress, and autonomic regulation in firefighters. Autopsy and case–control data indicate that most duty-related sudden cardiac deaths occur in the presence of underlying coronary atherosclerosis. Firefighters exhibit a high prevalence of cardiovascular risk factors, including hypertension (10%–44%), obesity (14%–60%), dyslipidemia (20%–56%), and metabolic syndrome (∼22%); these rates exceed those reported in age-matched general-population samples. Emergency operations are associated with marked sympathetic activation, hemodynamic stress, and circadian perturbation, which may promote plaque destabilization, myocardial ischemia, and ventricular arrhythmia. Additionally, occupational stress and sleep disturbance are linked to autonomic imbalance, potentially increasing arrhythmic susceptibility. Sudden cardiac death in firefighters reflects the interaction between baseline cardiometabolic risk and intermittent high-intensity physiologic stress rather than a distinct occupational disease entity. Early risk identification, guideline-directed therapy, and recognition of occupational stressors are central to cardiovascular risk reduction in this population.

Background: Catheter ablation is an established rhythm-control strategy for atrial fibrillation, yet the optimal timing of ablation in older patients with heart failure with reduced ejection fraction remains uncertain. Methods: We conducted a retrospective study using the TriNetX research network, including adults aged ≥ 60 years with atrial fibrillation and systolic heart failure who underwent catheter ablation between 2010 and 2022. Patients were classified by the timing of catheter ablation relative to cardiac diagnosis, with early ablation defined as occurring within 1 year and delayed ablation defined as occurring after 1 year. Propensity score matching (1:1) across 24 covariates was performed to balance demographics, comorbidities, medications, and baseline clinical characteristics. Outcomes assessed from 90 days blanking period to 3 years post-ablation included atrial fibrillation recurrence, heart failure exacerbation events, and all-cause hospitalization using risk, survival, and incidence analyses. Results: After matching, 678 patients were included in each cohort with well-balanced baseline characteristics. Atrial fibrillation recurrence did not differ significantly between early and delayed ablation groups (hazard ratio [HR] 0.71, 95% CI 0.39–1.28). In contrast, delayed ablation (>1 year) was associated with a significantly higher risk of heart failure events (HR 0.62, 95% CI 0.54–0.70) and shorter median heart failure-free survival compared with early ablation. All-cause hospitalization risk was similar between groups, although time-to-event analyses favored ablation within 1 year (HR 0.71, 95% CI 0.59–0.85). Conclusions: In this large, real-world cohort of older patients with atrial fibrillation and systolic heart failure, late ablation was associated with worse 3-years heart failure outcomes and delayed hospitalization-free survival, despite similar atrial fibrillation recurrence rates. These findings suggest that ablation timing may differentially influence heart failure progression independent of rhythm recurrence and highlight the need for prospective studies to define patient-specific timing strategies in elderly populations.