Objective: While depression has been linked to adverse cardiometabolic profiles in postmenopausal women, its temporal relationship with cardiovascular disease (CVD) when occurring before menopause remains unclear. This study examined whether depression diagnosed prior to menopause was associated with incident CVD after menopause. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Postmenopausal women were assigned to two cohorts: cohort 1 included women with depression diagnosed before menopause and without preexisting CVD, premature menopause, or conventional CVD risk factors (smoking, diabetes mellitus, hypertension, dyslipidemia, overweight/obesity, or family history of ischemic heart disease); cohort 2 included comparable women without premenopausal depression. Propensity score matching balanced baseline characteristics, including age at menopause, current age, and ethnicity. Risk differences and risk ratios (RRs) with 95% confidence intervals(CIs) were calculated to compare incident CVD (myocardial infarction, coronary heart disease, stroke, heart failure, or cardiovascular death). Time-to-event outcomes were assessed using Kaplan–Meier curves and log-rank testing, and hazard ratios (HRs) were estimated using Cox proportional hazards regression. Results: Initial queries identified 90,638 women in cohort 1 and 1,237,202 in cohort 2. After matching, 88,884 women remained in each cohort, with a mean (SD) age of 57.6(11.4) years. Follow-up varies according to database entry time, with maximum follow-up of 20 years. Women with premenopausal depression had a higher incidence of postmenopausal CVD than those without depression (4.0% vs. 3.3%; RR,1.23; 95% CI, 1.17–1.29; p<.001), corresponding to an absolute risk difference of 0.7% (95% CI, 0.6%–0.9%). Because the proportional hazards assumption was not satisfied, the Cox hazard ratio was interpreted as a secondary average time-to-event summary rather than as the primary effect estimate. The estimated hazard ratio for incident CVD was 1.21 (95% CI, 1.15–1.27; log-rank p<.001), representing an average association across the follow-up period rather than a constant hazard over time. Conclusion: Women with premenopausal depression had a higher cumulative incidence of postmenopausal cardiovascular disease than matched women without depression, suggesting that premenopausal depression may represent a marker of increased cardiovascular vulnerability in midlife women. Keywords: Depression, Cardiovascular diseases, Premenopausal, Postmenopausal, TriNetX
Background Atrial fibrillation (AF) frequently coexists with Heart Failure with Preserved Ejection Fraction, particularly in patients with Type 2 Diabetes, due to shared cardiometabolic and inflammatory mechanisms. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefit in HFpEF, but data regarding prevention of incident AF remain limited. Objectives To evaluate the association between SGLT2 inhibitor therapy and incident atrial fibrillation/flutter in patients with HFpEF and diabetes mellitus. Methods We performed a retrospective propensity score–matched cohort study using the TriNetX Research Network. Adults aged ≥18 years with HFpEF and diabetes mellitus receiving oral antihyperglycemic therapy were identified. Patients receiving SGLT2 inhibitors were matched 1:1 with those receiving Dipeptidyl peptidase-4 inhibitors. The primary outcome was incident AF/flutter. Secondary outcomes included all-cause mortality, ischemic stroke, and composite major adverse cardiovascular events (cMACE; all-cause mortality, ischemic stroke, or acute myocardial infarction). Associations were assessed using hazard ratios (HRs) and risk ratios (RRs). Results After propensity matching, 37,108 patients were included (18,554 per group). Compared with DPP4 inhibitor therapy, SGLT2 inhibitor use was associated with lower incidence of AF/flutter (17.8% vs 19.2%; HR 0.84, RR 0.93), all-cause mortality (12.5% vs 21.4%; HR 0.53, RR 0.59), ischemic stroke (7.4% vs 8.7%; HR 0.78, RR 0.85), and cMACE (24.4% vs 33.0%; HR 0.66, RR 0.74). Conclusions In patients with HFpEF and diabetes mellitus, SGLT2 inhibitor therapy was associated with lower rates of incident AF/flutter and adverse cardiovascular outcomes, supporting a potential role for SGLT2 inhibitors in modifying arrhythmic risk in addition to established cardiometabolic benefits.
Introduction: Anomalous Aortic Origin of Right Coronary Artery (AAORCA) is a rare congenital anomaly that may be associated with adverse cardiac events, including sudden cardiac death. Surgical correction is commonly recommended in patients with AAORCA. Coronary computed tomography angiography (CCTA) is a prevalent diagnostic modality, which increases AAORCA detection. However, the clinical significance of incidentally detected AAORCA remains unclear. Methods: This non-randomized retrospective analysis included 10,134 patients who underwent CCTA between January 2014 and December 2022, either for suspected coronary artery disease (CAD) or a medical check-up. Three groups were created: patients with normal coronary anatomy (normal), with AAORCA (anomaly), and CAD without AAORCA (CAD). CAD was defined as a percentage diameter stenosis of ≥50% in one or more segments. Cardiac mortality was this study’s primary endpoint. Results: Normal, anomaly, and CAD group comprised 7592 (74.9%), 66 (0.7%), and 2476 (24.4%) patients, respectively. During a median follow-up of 33.7 months (IQR: 13.2–53.4), Kaplan-Meier analysis revealed no significant difference in the cardiac death occurrence between the normal (15 events, 0.2%) and anomaly groups (0 events, 0%) (log-rank p=0.685). Cox proportional hazards model revealed no difference in mortality in the anomaly group compared with normal group. Conclusions: In our cohort, incidentally detected AAORCA in adults did not demonstrate a clearly elevated cardiac death risk relative to CAD during mid-term follow-up. However, given the small number of events, these findings should be interpreted as descriptive rather than confirmatory evidence of a benign natural course, particularly in populations at higher risk of exertional sudden cardiac death.
Objectives: This study aimed to investigate cardiac dysfunction in patients with mild focal left ventricular hypertrophy (MF-LVH) by analyzing the left ventricular (LV) and left atrial (LA) deformation parameters derived from cardiac magnetic resonance feature tracking (CMR-FT). Methods: This retrospective study included 36 patients with MF-LVH, 44 patients with HCM without late gadolinium enhancement (HCM-non-LGE), and 32 healthy controls who were examined between November 2020 and August 2025. The LA and LV strain parameters were obtained using CMR-FT. Statistical comparisons, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were conducted. Results: While conventional parameters showed no difference, all global LV strains and most strain rate parameters were significantly impaired in both patient groups, showing a stepwise decline with advancing hypertrophy severity. In multivariable analyses, the peak diastolic radial strain rate (PD-RSR) was the primary discriminator distinguishing MF-LVH from controls, and LV global longitudinal strain (LV-GLS) was the key discriminator differentiating MF-LVH from HCM-non-LGE. LV-GLS and LA minimal volume index (LAVImin) were the key discriminators for HCM-non-LGE versus controls. ROC analysis confirmed LV-GLS as an excellent discriminator (AUC 0.85 for MF-LVH vs. HCM-non-LGE; AUC 0.96 for HCM-non-LGE vs. controls), with notably similar optimal cutoff values (-13.94% and -13.99%, respectively). PD-RSR showed good accuracy in identifying MF-LVH. Conclusion: PD-RSR indicates early diastolic impairment, and LV-GLS sensitively detects systolic dysfunction in patients with MF-LVH. The overlapping LV-GLS values between patients with MF-LVH and HCM-non-LGE suggest a potential pathophysiological continuum. CMR-FT enables early detection of subclinical myocardial dysfunction in this population.
Introduction: Electrocardiographic (ECG) criteria for left atrial enlargement (LAE) serve as clinical surrogates for structural and hemodynamic left atrial (LA) overload. Their diagnostic performance compared to echocardiography remains suboptimal, and African Americans are consistently underrepresented in relevant diagnostic accuracy studies. Methods: We performed a cross-sectional analysis of the Jackson Heart Study (JHS), a large community-based cohort of African American adults (aged 21–94 years). P-wave duration was evaluated as the index test across continuous thresholds using receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) with 95% confidence intervals (95% CI). The main reference standard was echocardiographic LAE defined by American Society of Echocardiography (ASE) sex-specific left atrial (LA) two-dimensional (2D) diameter thresholds (>40 mm in men; >38 mm in women). Results: A total of 3,572 participants were included, of whom 647 (18.1%) met ASE diameter criteria for LAE. Overall discriminatory performance was poor (AUC 0.603; 95% CI 0.580–0.627). At the traditional ≥120 ms threshold, sensitivity (Sn) was 58.3% (95% CI 54.4–62.1%), specificity (Sp) was 56.8% (95% CI 55.0–58.6%), positive likelihood ratio (LR+) was 1.35 (95% CI 1.25–1.46), and negative likelihood ratio (LR-) was 0.73 (95% CI 0.67–0.81), reflecting limited capacity to rule in or out LAE. Conclusion: In this cohort, P-wave duration demonstrated poor diagnostic accuracy for diameter-defined echocardiographic LAE. These findings highlight the inadequacy of this ECG criterion as a surrogate marker across a historically underrepresented population. Machine learning models may offer a path forward for higher performance of ECG as a screening tool for LAE in African Americans.
