Adverse Outcomes Research Articles

Background: Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (CHD) after transcatheter pulmonary valve replacement (TPVR), likely due to preexisting myocardial dysfunction and suboptimal reverse remodeling. Left ventricular (LV) diastolic dysfunction, unmasked by an acute increase in preload post-TPVR, may elevate left-sided filling pressures and precipitate pulmonary edema. However, the prognostic implications of elevated left-sided filling pressures prior to TPVR are currently unknown. Objective: To evaluate the prognostic value of pre-TPVR pulmonary artery wedge pressure (PAWP) and the heart failure with preserved ejection fraction – Age, Body mass index (BMI), Atrial fibrillation (HFpEF-ABA) score in patients undergoing TPVR. Methods: Adults with congenital heart disease (CHD) undergoing TPVR were stratified by pre-implant PAWP (<15 vs ≥15 mmHg) and HFpEF-ABA score (low <25%, intermediate 25–75%, high >75%). The composite endpoint was all-cause mortality, heart transplantation, heart failure (HF) hospitalization, or sustained ventricular arrhythmia. Kaplan-Meier and Cox regression analyses assessed associations with clinical outcomes. Results: Out of 150 patients, 37 (24.7%) had PAWP ≥15 mmHg. Elevated PAWP was associated with older age (36 [31;53] vs. 26 [19; 37] years, p<0.01), BMI (27.9 [24.5; 35.1] vs. 24.2 [20.6; 29.7] kg/m 2 , p<0.01), and higher HFpEF-ABA score (42.8 [9.5;63.6] vs. 6.4 [2.5;18.1]%, p<0.001) compared to normal PAWP. Over a median follow-up of 38 [13; 83] months, 26 events (17.3%) occurred. Kaplan-Meier analysis demonstrated a significant difference in event-free survival based on pre-TPVR PAWP categories (log-rank p=0.002) and HFpEF-ABA score categories (log-rank p<0.001). Elevated PAWP was associated with adverse outcomes (hazard ratio [HR] 4.27, 95% CI 1.61–11.31, p=0.003) (Figure 1), but this was no longer significant after age adjustment. HFpEF-ABA ≥25% was associated with adverse outcomes (HR 10.6, 95% CI 3.8–30.0, p<0.001) (Figure 2), independent of N-terminal prohormone of brain natriuretic peptide levels and left ventricular ejection fraction. Conclusion: Albeit confounded by demographics, pre-TPVR PAWP correlated with adverse long-term outcomes, and patients with this hemodynamic profile may require closer post-procedural surveillance. HFpEF-ABA was independently associated with incident events, representing an inexpensive, novel prognostic tool in patients undergoing TPVR.

Background: Recent updated guidelines recognize catheter ablation as a first-line therapy for symptomatic atrial fibrillation (AF). The optimal timing of catheter ablation following AF diagnosis remains uncertain. This study assessed the impact of diagnosis-to-ablation time (DAT) <1 year versus DAT ≥1 year on AF recurrence and adverse clinical outcomes. Hypothesis: We hypothesize that earlier DAT reduces AF recurrence and adverse outcomes by decreasing atrial remodeling associated with AF. Methods: We queried the TriNetX research network for patients ≥18 years of age with AF who underwent ablation between January 1, 2010, and June 30, 2019. Patients were stratified based on DAT <1 year vs. DAT ≥1 year and matched using 1:1 propensity scoring for relevant factors. The primary outcome was AF recurrence, defined as a composite of cardioversion, antiarrhythmic drug (AAD) use, or re-ablation at 3 and 5 years, after a 3-month blanking period. Secondary outcomes included a composite of heart failure exacerbation, ischemic stroke, all-cause hospitalization, and mortality along with individual components. Results: A total of 17,683 patients with DAT <1 year and 13,939 patients with DAT ≥1 year were identified. Propensity matching (1:1) resulted in 9,566 patients in each cohort. The two cohorts were balanced for all baseline covariates except index age, with DAT≥1 being marginally older (63.2 ± 10.0 vs. 63.5 ±10.1, p=0.026). DAT <1 year was associated with significantly lower AF recurrence both at 3 years (adjusted OR: 0.725; 95% CI: 0.683-0.770; p<0.001) and 5 years (adjusted OR: 0.707; 95% CI: 0.667-0.750; p<0.001). The secondary composite outcome was also significantly lower in the DAT <1 year group both at 3 years (adjusted OR 0.84 [95% CI: 0.78–0.89]; p < 0.001) and 5 years (adjusted OR 0.80 [95% CI: 0.76–0.85]; p < 0.001). At 3 years, secondary individual outcomes significantly reduced in the DAT <1 year group included cardioversion, AAD use, ischemic stroke, and all-cause hospitalization. At 5 years, secondary individual outcomes significantly reduced in the DAT <1 year group included cardioversion, re-ablation, AAD use, heart failure exacerbation, ischemic stroke, and all-cause hospitalization. (Figure) Conclusion: Catheter ablation within one year of AF diagnosis is associated with reduced AF recurrence and major adverse clinical outcomes. These findings support early referral for ablation to improve long-term outcomes.

Background: Renal congestion is recognized as an important factor related to adverse outcomes in heart failure patients. Although transcatheter aortic valve implantation (TAVI) improves hemodynamic status in patients with severe aortic stenosis, the prognostic significance of renal congestion in the pre- and post-TAVI settings remains unclear. Therefore, we investigated its association with adverse outcomes following TAVI. Methods and Results: A total of 164 consecutive patients with severe aortic stenosis who underwent intrarenal Doppler ultrasonography both pre- and post-TAVI were enrolled. To assess renal congestion, intrarenal venous flow (IRVF) patterns were evaluated and categorized into two morphological types: a discontinuous pattern suggesting renal congestion and a continuous pattern indicating normal venous flow. Of the 164 patients, 38 patients (23.2%) exhibited a discontinuous IRVF pattern pre-TAVI, while 30 patients (18.3%) showed a discontinuous pattern post-TAVI. Patients were separately classified based on pre- and post-TAVI IRVF patterns, and the primary endpoint was defined as a composite of all-cause death or heart failure rehospitalization. During a median follow-up period of 698 days, a total of 37 patients (22.6%) experienced the composite outcome. Kaplan–Meier analysis showed no significant difference in the incidence of the composite outcome between the two groups classified by pre-TAVI IRVF patterns (log-rank P = 0.295, Figure A). In contrast, Kaplan–Meier analysis based on post-TAVI IRVF patterns demonstrated significantly worse outcomes in patients with a discontinuous pattern (log-rank P = 0.005, Figure B). In multivariable Cox regression analysis adjusted for age and sex, a discontinuous IRVF pattern post-TAVI remained independently associated with the composite outcome (HR 2.11, 95% CI 1.03–4.33, P = 0.042). Subgroup analyses stratified by clinical variables such as estimated glomerular filtration rate, B-type natriuretic peptide, and hemoglobin showed consistent results, indicating no significant interactions observed. Conclusions: Post-TAVI renal congestion, as indicated by a discontinuous IRVF pattern, was independently associated with adverse clinical outcomes following the procedure.

Background: Paradoxical low-flow, low-gradient (PLFLG) severe aortic stenosis (AS) is a high-risk phenotype characterized by low transvalvular gradients despite preserved left ventricular ejection fraction (LVEF). While stroke volume index is conventionally used to define flow state, transvalvular flow rate (Q)—a measure incorporating both volume and ejection duration— offers a more physiologic assessment of forward flow. Given known sex-based differences in flow dynamics, we aimed to evaluate whether sex-specific Q thresholds are associated with adverse outcomes in PLFLG severe AS. Methods: We included 1,189 patients with adjudicated PLFLG severe AS (aortic valve area <1.0 cm2, mean gradient <40 mmHg, LVEF ≥50%, and Q ≤210 mL/sec) from an institutional echocardiographic database. Sex-specific Q thresholds were derived using the maximally selected rank statistic (≤150 mL/sec in males, ≤180 mL/sec in females). The primary outcome was a composite of all-cause mortality and aortic valve replacement (SAVR/TAVR). Results: In both sexes, lower Q was associated with a smaller aortic valve area, lower stroke volume index and reduced transvalvular gradients. Patients with low Q had significantly lower event-free survival, particularly among females, for both all-cause mortality and the composite outcome (log-rank p<0.001)(Figure). In a multivariable analysis, low Q independently predicted adverse composite outcome in both males (HR 1.54, 95% CI: 1.10–2.16) and females (HR 1.39, 95% CI: 1.16–1.65). Conclusion: Sex-specific transvalvular flow rate thresholds are independently associated with adverse outcomes in paradoxical low-flow low-gradient severe aortic stenosis. These findings support the clinical utility of sex-specific Q, particularly in women, for refining risk stratification and guiding timely intervention.

Background: Obesity is a well-established risk factor for cardiovascular diseases, including atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce AF burden and adverse cardiac outcomes through weight loss and metabolic improvements. Objective: To assess whether GLP-1 RA use is associated with reduced incidence of atrial fibrillation and other adverse outcomes among obese patients (BMI ≥35 kg/m2). Methods: A retrospective cohort study was conducted using the TriNetX global federated health research network, encompassing 103 healthcare organizations. Adults with BMI ≥35 kg/m2 between October 1, 2022 and December 31, 2022 were identified. Patients prescribed GLP-1 RAs (n = 74,539) were compared to propensity score-matched controls not using GLP-1 RAs (n = 74,539). Outcomes included atrial fibrillation (ICD-10 I48), all-cause mortality, major adverse cardiovascular events (MACE), and changes in BMI. Analyses included risk ratios, risk differences, odds ratios, and Kaplan-Meier survival statistics. Results: GLP-1 RA use was associated with lower incidence of AF (8.4% vs 8.9%; risk difference -0.4%, 95% CI [-0.7%, -0.1%]; risk ratio 0.95, 95% CI [0.92–0.98]; p=0.003) and reduced all-cause mortality (1.7% vs 2.6%; risk difference -0.9%, 95% CI [-1.0%, -0.7%]; risk ratio 0.67, 95% CI [0.62–0.72]; p<0.001). MACE risk was also lower in the GLP-1 RA group (6.8% vs 7.8%; risk difference -1.1%, 95% CI [-1.3%, -0.8%]; risk ratio 0.87, 95% CI [0.84–0.90]; p<0.001). Mean BMI at follow-up was slightly higher in the GLP-1 RA group (40.16 vs 39.87 kg/m2; p<0.001). Kaplan-Meier analysis confirmed significant reductions in AF and mortality risk (log-rank p<0.001 for both). Conclusions: Among obese patients, GLP-1 RA use was associated with a modest reduction in atrial fibrillation incidence, lower rates of major adverse cardiovascular events, and reduced all-cause mortality compared to matched controls. These findings support the potential cardioprotective effects of GLP-1 RAs in high-risk obese populations.

Background: Transcatheter aortic valve replacement (TAVR) has emerged as a transformative, minimally invasive alternative to surgical aortic valve replacement for patients with trileaflet aortic stenosis. While the use of TAVR continues to expand, limited data exist regarding contemporary trends and clinical outcomes associated with TAVR with and without percutaneous coronary intervention (PCI) during the same hospitalization. Methods: The National Inpatient Sample database from 2018 to 2022 was used, and regression analysis was performed. Results: Among 323,785 patients with a primary diagnosis of aortic stenosis and a history of coronary artery disease, 211,125 (65.2%) underwent TAVR alone (TAVR), while 5,900 (1.8%) underwent TAVR and PCI (TAVR+PCI) during the same index hospitalization. Compared to TAVR only group, patients in the TAVR+PCI group were more often female (43% vs 37%, p<0.001), less often White (83% vs 88%, p=0.0001), and more often in the highest income quartile (76th–100th percentile: 30% vs 26%, p=0.03). The prevalence of Charlson Comorbidity Index ≥3 was comparable between groups (57% vs 54%, p=0.25), and no significant age difference was observed. Multivariable logistic regression identified the Charlson Comorbidity Index ≥3 as an independent predictor of in-hospital mortality. Adjusted analyses revealed that the TAVR+PCI group had a higher incidence of major adverse cardiovascular events (MACE), including in-hospital mortality (3% vs 1%, p<0.001), acute myocardial infarction (11% vs 1%, p<0.001), and acute heart failure (40% vs 27%, p<0.001) although, stroke rates, both ischemic and hemorrhagic, were similar between 2 groups (2% vs 2%, p=0.06). Patients undergoing TAVR+PCI experienced longer hospital stays (mean 6.3 vs 2.7 days, p<0.001) and incurred higher hospitalization costs (mean $319,731 vs $211,120, p<0.001) compared to those undergoing TAVR alone. This study also showed TAVR+PCI group suffered more adverse in-hospital outcomes compared to TAVR only group [Table]. Conclusion: This study indicates that concomitant TAVR and PCI is associated with higher rates of mortality, acute myocardial infarction, and heart failure compared to TAVR alone. Other studies have indicated that the strategy of performing PCI within 90 days prior to TAVR may mitigate such adverse outcomes.

Background: There are currently no robust clinical markers for assessing prognosis in patients with heart failure (HF) with recovered left ventricular ejection fraction (LVEF). Hypothesis: We hypothesized that N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at the time of LVEF recovery is an independent predictor of LVEF relapse and adverse clinical outcomes in patients with HF with recovered LVEF. Methods: This retrospective cohort study (2009–2024) included 3935 patients with HF with recovered LVEF (≥50%) and available NT-proBNP data at the time of LVEF recovery. Patients were categorized into seven NT-proBNP groups, which were compared using Kaplan-Meier analysis and multivariable Cox regression to evaluate the outcome of LVEF relapse (decrease by ≥10% to <50%) and the composite outcome of HF hospitalization or all-cause death. NT-proBNP was also modeled as a continuous variable using natural cubic splines. Utilization of medications constituting guideline-directed medical therapy (GDMT) was compared across NT-proBNP groups at 6 months of follow-up. Results: The median value of baseline NT-proBNP was 1341 pg/mL (IQR, 400–4207). In general, the probability of remaining free from LVEF relapse and the composite outcome decreased across NT-proBNP groups. In the fully adjusted multivariable Cox regression model, NT-proBNP was an independent predictor of both LVEF relapse and the composite outcome, with higher NT-proBNP levels associated with higher risk of both outcomes in a dose-response manner. Notably, even near-normal NT-proBNP levels (125–299 pg/mL) were associated with poorer prognosis relative to normal levels (<125 pg/mL), with a 46% higher risk of LVEF relapse and 82% higher risk of the composite outcome. This relationship was consistent across age, sex, atrial fibrillation status, and renal function, but was modified by body mass index (BMI), with higher BMI associated with higher risk. NT-proBNP was even predictive of the composite outcome when patients sustained LVEF recovery and did not experience LVEF relapse. Patients with higher baseline NT-proBNP levels did not have higher utilization of GDMT medications at 6 months of follow-up, and in some cases even had lower utilization. Conclusions: NT-proBNP is an independent and robust predictor of prognosis in patients with HF with recovered LVEF, warranting routine measurement of NT-proBNP in these patients for further GDMT optimization.

Background: Autoimmune diseases affect ~10% of the population, the overwhelming majority of which are women. However, the impact of autoimmune disease, such as systemic lupus erythematosus (SLE), on outcomes following myocardial infarction (MI) are not well understood. Thus, we hypothesized that cardiac function and remodeling would be impaired following MI in a pristane-induced model of SLE. Methods: Adult female C57BL/6J mice were given a single injection of pristane 3 months prior to MI surgery. The left coronary artery was then permanently ligated for either 7, 28, or 56 days (D). Echocardiography was performed to assess cardiac function. Tissues were then collected for flow cytometry, including blood, kidney, and left ventricle (LV), which was separated into infarcted and remote areas. Plasma IgG was assessed by ELISA. LV cytokines were measured by real-time PCR. Results: Development of the SLE phenotype was confirmed by elevated levels of plasma IgG. SLE resulted in worse cardiac function at each time point, including LV dilation (increased internal diameter at diastole and end-diastolic volume), wall thinning, and decreased ejection fraction. SLE mice also had elevated wet lung weights at each time point, an indicator of pulmonary congestion. At D7, mRNA levels of inflammatory cytokines Il6 and Il18 were elevated in the infarct, while Col1a1 and Pecam1 were decreased, indicating impaired remodeling. At D7, SLE mice had increased LV CD45+ cells (p=0.003) and B cells (p=0.056), as well as circulating neutrophils (p=0.047). MI also led to expansion of total CD45+ cells, T cells, monocytes, and neutrophils in the kidney, with SLE exacerbating kidney neutrophil expansion (p=0.01). At D56, SLE mice had increased inflammatory cells in the remote area, including total CD45+ cells (p=0.03), CD3+ T cells (p<0.0001), and CD8+ T cells (p=0.003), and increased kidney CD45+ cells (p=0.03), neutrophils (p=0.002), and monocytes (p<0.0001). To investigate potential mechanisms associated with adverse outcomes in SLE, we measured genes associated with the type I interferon response at in the LV at D7. Ifng , Ifna2 , Ifnb1 , Ifne , Ifnar1 , and Irfs 1, 2, 5, 7 , and 9 were increased, but this effect was surprisingly attenuated in SLE. Conclusions: SLE is associated with adverse post-MI outcomes, including cardiac remodeling and inflammation, pulmonary congestion, and renal inflammation. These effects are associated with perturbation of the type I interferon response.

Background: Pediatric pulmonary hypertension can be diagnosed by echocardiography and right heart catheterization, but cardiac MRI-based septal curvature (SC) measurement can also be used as a surrogate of mean pulmonary arterial pressure (mPAP), which is an invasive measurement to follow-up patients. We developed an automated approach to measure SC, demonstrating its superiority over a manual measurement. However, its performance relative to other septal wall measurements and clinical markers are unclear. Hypothesis: Automated SC is better correlated with mPAP, less observer dependent, and better associated with adverse outcomes than interventricular septal angle (IVS) and right ventricular ejection fraction (RVEF). Aims: To compare the automated SC, IVS, and RVEF in terms of observer variability, correlation to mPAP, and correlation with adverse outcomes. Methods: Patients with pulmonary hypertension who had both catheterization and cardiac MRI were retrospectively included. Automated SC and IVS were measured using a mid-slice of short-axis stack imaging for both ventricles using cvi42, a custom MATLAB tool and Fuji PACs (Fig.1). RVEF was collected from the MRI scan report. Adverse outcomes were death, transplant, and/or indication for transplant of heart and/or lung and were collected from electronic health record. Pearson correlation was used for correlation between the metrics and mPAP. A receiver-operating characteristic (ROC) curve was used to investigate the association between the metrics and outcomes. Intraclass correlation coefficient (ICC) was used for interobserver variability analysis. P<0.05 was considered statistically significant. Results: 25 patients (17.0 [12.0 – 18.0] years; 13 with adverse outcomes) were included. Automated SC had a better correlation with mPAP (R=-0.82, p<0.001) than IVS (R=0.66, p<0.001) and RVEF (R=-0.49, p=0.01) (Fig.2). The capability to differentiate adverse outcomes was significant and better for RVEF (area under the curve of 0.82, p=0.007) while it was not significant for automated SC (0.72, p=0.06) and IVS (0.63, p=0.28) (Fig.3). Interobserver analysis found comparable ICCs (0.98, 95%CI, 0.97 – 0.99 for automated SC; 0.97, 95%CI 0.94 – 0.98 for IVS). ICC was not estimated for RVEF due to retrospective nature of the data collection. Conclusion: The automated SC better correlated with mPAP, with comparable observer dependency to IVS but was not able to better differentiate adverse outcomes than RVEF.

Background: Among Asian populations, there have been limited reports on the impact of cardiovascular-kidney-metabolic (CKM) syndrome stages on adverse cardiovascular outcomes. This study aims to explore the association between CKM stages and adverse cardiovascular outcomes in a Beijing community population Methods: This study was a prospective cohort analysis conducted on a community-based Chinese population. The primary endpoint encompassed major adverse cardiovascular events (MACE), specifically cardiovascular death, acute myocardial infarction (AMI), or stroke. Conversely, secondary endpoint events encompassed cardiovascular death, AMI, stroke, or all-cause mortality. Cox regression models were employed to examine the associations between various stages of CKM and adverse cardiovascular outcomes. Results: A total of 9,400 participants were enrolled in the study, with a median follow-up duration of 9.9 (9.8-10.0) years. During this period, there were 1,060 MACE, 179 cardiovascular deaths, 205 AMI, 841 strokes, and 541 all-cause deaths. The multivariate Cox model revealed that, compared with participants in the stage 0, those in the stage 2 exhibited a significantly elevated risk of MACE (HR=2.74; 95%CI: 1.49–5.06; P =0.001) and stroke (HR=2.78; 95%CI: 1.41–5.47; P =0.003). Participants in the stage 3 demonstrated a marked increase in the risk of MACE (HR=4.32; 95%CI: 2.32–8.05; P <0.001), AMI (HR=8.85; 95%CI: 1.19–65.84; P =0.033), and stroke (HR=4.15; 95%CI: 2.08–8.27; P <0.001). Furthermore, those in the stage 4 showed a substantial increase in the risk of MACE (HR=7.32; 95%CI: 3.93–13.63; P <0.001), cardiovascular death (HR=6.06; 95%CI: 1.41–26.07; P =0.016), AMI (HR=11.88; 95%CI: 1.59–88.75; P =0.016), stroke (HR=7.39; 95%CI: 3.71–14.70; P <0.001), and all-cause mortality (HR=2.13; 95%CI: 1.18–3.86; P =0.012). Subgroup analysis and interaction test discovered no significant interactions between stages of CKM and other risk factors, including age, sex, body mass index, homocysteine, glomerular filtration rate, smoking and drinking status(the P values for interactions were all greater than 0.05). Conclusions: Our research indicates that advanced stages of CKM syndrome are linked to an increased risk of MACE, cardiovascular death, AMI, stroke and all-cause mortality. It is imperative to devise tailored management strategies for each phase of CKM syndrome in order to alleviate the healthcare burden.

Introduction: Peripheral artery disease (PAD) is a known risk factor for adverse cardiovascular outcomes and has historically been viewed as a relative contraindication to heart transplantation (HT). However, as management of PAD improves and transplant eligibility broadens, the impact of PAD on post-HT outcomes warrants reevaluation. Hypothesis: Pre-HT PAD, driven by extremity PAD, is associated with increased risk of 1-year post-HT adverse outcomes, including all-cause mortality, cerebrovascular accident (CVA), renal replacement therapy (RRT), graft dysfunction, and adverse vascular outcomes. Methods: We conducted a retrospective cohort study of patients who underwent HT at a large, advanced heart failure center from January 2012 to May 2022. PAD was defined by history of CVA, claudication, abnormal ankle-brachial index (ABI <1), abnormal carotid dopplers (>50% stenosis), or abnormal upper or lower extremity arterial dopplers (>50% stenosis). Patients were stratified by PAD status and subtype: central/cerebrovascular (CVA or abnormal carotid dopplers) and extremity (claudication, abnormal ABI, or abnormal extremity dopplers). Outcomes included 1-year all-cause mortality, CVA, RRT, graft dysfunction (ejection fraction <55%), and vascular complications (consults or abnormal imaging). Group comparisons used multivariable logistic regression adjusted for PAD subtype using Python®. Results: Of the 595 patients (mean age 53 years; 28% female; 27% Black), 216 (36%) had PAD. The PAD group exhibited higher rates of pre-HT diabetes (32% vs 21%, p<0.01) and hypertension (58% vs 44%, p<0.01). No significant differences in age, sex, race, kidney disease, or smoking were found between groups. In the PAD group, one-year all-cause mortality was more than double those without PAD (11.6% vs 5.5%, p=0.01). Graft dysfunction was also higher (16.7% vs 9.8%, p=0.02), while CVA (9.3% vs 8.4%, p=0.85) and RRT (15.7% vs 10.8%, p=0.11) were not significantly different in PAD patients compared to those without. PAD patients also had increased vascular complications at 1 year (15.3% vs 5.3%, p<0.001). However, when stratified by PAD subtype, neither central/cerebrovascular nor extremity PAD independently predicted outcomes (Figure). Conclusion: Total PAD burden pre-HT was associated with increased all-cause mortality, graft dysfunction, and vascular complications at 1 year. These findings underscore the importance of incorporating PAD into pre- and post-HT management.

Background: Sex differences in coronary physiology have been reported, particularly with regard to higher resting coronary flow in women. Resting flow is independently associated with clinical outcomes, irrespective of the presence of coronary microvascular dysfunction (CMD), but its sex-specific prognostic significance remains unclear. Aims: This study aimed to compare the prognostic implications of resting flow and CMD between sexes among patients with angina and non-obstructive coronary arteries (ANOCA). Methods: We studied 1194 patients with ANOCA undergoing coronary reactivity testing. Endothelium-independent microvascular function was assessed by coronary flow reserve (CFR) during adenosine-induced hyperemia, and endothelium-dependent function by coronary blood flow (CBF) increase during intracoronary acetylcholine infusion. Endothelium-dependent CMD was defined as <50% CBF increase, and endothelium-independent CMD as CFR <2.5. Cardiovascular events were defined as a composite of all-cause death, myocardial infarction and heart failure. Results: The median age of the study population was 52 years, and 71.1% were women. Resting average peak velocity (rAPV) and baseline CBF (bCBF) were significantly higher in women (p<0.001 and p=0.006, respectively). Survival analysis revealed that both elevated rAPV and bCBF were significantly associated with worse outcomes in men (p<0.001 and p=0.036, respectively, Figure 1), whereas no such associations were observed in women. In Cox proportional hazard analysis, sex showed a significant interaction effect with elevated rAPV (interaction p=0.014). Furthermore, endothelium-independent CMD was significantly associated with adverse outcomes in both men and women (p=0.011 and p=0.004, respectively), whereas endothelium-dependent CMD was significantly associated with prognosis only in men (p=0.006). Among men with endothelium-dependent CMD, the subtype characterized by higher bCBF was particularly associated with worse prognosis (p=0.001, Figure 2). Conclusions: In patients with ANOCA, men had lower resting coronary flow than women. However, its association with adverse outcomes was observed only in men, especially in those with impaired endothelial function. These results suggest that coronary physiology should be interpreted differently by sex, and that clinical decisions should be adjusted accordingly.

Background: Cardiovascular disease is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have proven to be beneficial in improving cardiovascular outcomes and reducing all-cause mortality in patients withT2DM. We aimed to investigate the effect SGLT2i use on cardiovascular outcomes inpatients with T2DM who underwent VT ablation. Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Network, a federated network of healthcare organizations across the United States. Adults (aged 18–80 years) with T2DM who underwent catheter ablation for ventricular tachycardia were included. Patients were stratified based on exposure to SGLT2i. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes were assessed within 3 years following the index ablation procedure. Patients with a recorded occurrence of the outcome prior to the index event were excluded from each respective outcome analysis. Kaplan-Meier analysis and log-rank tests were used for statistical comparisons with significance set at p<0.05. Results: SGLT2 inhibitor non-users exhibited significantly higher hazard ratios (HR) for various adverse outcomes. The HR for all-cause mortality was 1.422 (95% CI: 1.279–1.581), while the HR for cardiac arrest was 1.409 (95% CI: 1.135–1.750). Additionally, the HR for post-ablation cardioversion was 1.188 (95% CI: 1.042–1.355), and the utilization of amiodarone after ablation had an HR of 1.240 (95% CI: 1.106–1.391). In contrast, the hazard ratios for redo ablation (1.039, 95% CI: 0.956–1.128), visits for ICD adjustments (0.916, 95% CI: 0.766–1.096), post-ablation use of any class of antiarrhythmics (1.139, 95% CI: 0.906–1.431), and lidocaine (0.911, 95% CI: 0.775–1.070) were less definitive. Conclusion: SGLT2i non-user group was associated with significantly higher risks of several adverse outcomes following ablation, including a 42% increase in all-cause mortality and a 41% increase in cardiac arrest. Non-users also had higher rates of post-ablation cardioversion and amiodarone use. However, no significant differences were found in redo ablation, ICD adjustments, or the use of other antiarrhythmics. These findings suggest a potential protective role of SGLT2 inhibitors in selective cardiovascular outcomes. Further studies are warranted to confirm these associations and investigate the underlying mechanisms.

Background: Preeclampsia is a heterogeneous disorder, with emerging evidence indicating the presence of multiple phenotypes. Identifying distinct clinical phenotypes may facilitate precise therapies and improve the clinical outcomes. This study aims to identify and validate preeclampsia phenotypes using machine learning and evaluate their associations with adverse pregnancy outcomes. Hypothesis: Machine learning-based clustering methods applied to routinely-collected clinical variables can identify distinct preeclampsia phenotypes, each associated with unique clinical profiles and differential risks of adverse pregnancy outcomes. Methods: In the derivation cohort (n=2,386), phenotypes were derived using k-means clustering applied to 26 routinely-collected clinical variables. A machine learning classifier incorporating key biomarkers was developed and externally validated to assign phenotypes within the validation cohort (n=1,570). Biological markers, clinical outcomes (primary outcome: composite of small for gestational age [SGA], preterm delivery, stillbirth, and neonatal death), and heterogenous impacts of delivery timing in term preeclampsia were analyzed across phenotypes. Results: Four distinct phenotypes were identified in the derivation cohort. Phenotype A exhibited hypocoagulation, while Phenotype B displayed relative thrombocytopenia. Phenotype C demonstrated hypercoagulation, and Phenotype D presented with hepatic and renal dysfunction, elevated potassium, and coagulation abnormalities. These findings were replicated in the validation cohort. Compared with Phenotype A, Phenotype D had the highest risk for the primary outcome (relative risk [RR] 2.83, 95% CI 2.48–3.23, P < 0.001), followed by Phenotypes C (RR 1.72, 95% CI 1.49–1.99) and B (RR 1.28, 95% CI 1.08–1.50). In term preeclampsia, delivery at 37 weeks increased adverse outcome risks relative to after 40 weeks in Phenotypes A, B, and D; Phenotype C exhibited elevated risks from 37–39 weeks. Conclusion: Four clinical phenotypes of preeclampsia were identified by using routinely-collected health data, each characterized by unique maternal feature profiles and associated with varying fetal outcomes. These phenotypes reflect diverse underlying pathophysiological processes, and may inform individualized decisions regarding delivery timing. Machine learning-based phenotyping represents a promising strategy to advance precision obstetrics and improve the understanding and management of preeclampsia.

Introduction: Serious mental illness (SMI), defined as schizophrenia, major depressive disorder, or bipolar disorder, has been associated with an increased risk of a variety of adverse maternal and fetal outcomes. Research has demonstrated a higher comorbidity burden in these patients, including obesity, T2DM, epilepsy, thyroid disease, and substance use disorders. We attempted to investigate the risk for adverse maternal cardiovascular outcomes in patients with SMI while controlling for comorbidity burden. Methods: Using the National Inpatient Sample from 2020 to 2022, we retrospectively identified patients ≥18 years of age who were admitted for a childbirth. Patients hospitalized for abortions, ectopic pregnancy, and stillbirths were excluded. Baseline characteristics were compared using t-tests. A multivariable logistic regression model with a 2-sided significance level of 0.05 was used. Results: A total of 10,425,907 deliveries were included in the analysis, of which 700,852 (6.7%) occurred in patients with serious mental illness (SMI). The specific SMI diagnosis and overall distribution are given in image-1. The SMI group had a higher prevalence of comorbidities, including systemic HTN, T2DM, CAD, systolic/diastolic HF, COPD, and CKD 3-5. The mean maternal age was similar between groups. The baseline characteristics are given in image-2. Multivariate analysis was run after adjusting for all baseline characteristics. SMI was associated with an increased odds of post/peripartum cardiomyopathy (aOR 2.28, 95% CI 1.76–2.95, p<0.001), post-delivery shock (aOR 1.66, 95% CI 1.47–1.86, p<0.001), acute systolic or diastolic HF exacerbation (aOR 2.08, 95% CI 1.49–2.89, p<0.001), and paroxysmal tachycardia or atrial fib/flutter (aOR 2.24, 95% CI 1.68–2.98, p<0.001). Cardiogenic shock showed a trend toward significance (aOR 1.81, 95% CI 0.96–3.41, p=0.066). There was no significant association with maternal inpatient mortality or acute right heart failure. Spontaneous coronary artery dissection was omitted from analysis due to zero events in the SMI group. Conclusion: Serious mental illness is independently associated with increased odds of adverse maternal cardiovascular outcomes. This analysis is limited to inpatient data; we could not assess outcomes following hospital discharge. Additional cases of delayed post-partum cardiomyopathy and other complications may have occurred after discharge, which were unable to be captured.

Prior studies have not identified if continuous glucose monitoring (CGM) metrics at a critical gestational age window can discriminate risk of adverse pregnancy outcomes. We evaluated late second- and third-trimester CGM metrics by gestational age associated with pregnancy outcomes in gravidas with type 1 diabetes (T1DM). Dexcom G6 CGM data from a retrospective cohort of singleton gestations with T1DM (2018-2022) at an academic medical center were analyzed. Time in, above, and below range 63 to 140 mg/dL (TIR, TAR, TBR), glycemic variability, and mean glucose concentration were computed in two-week CGM intervals from 240 to 396 weeksdays. Adverse pregnancy outcomes were hypertensive disorders of pregnancy (HDP), large-for-gestational age (LGA), and neonatal hypoglycemia. Linear mixed-effects models were fitted on CGM metrics computed from two-week CGM intervals, with gestational age, adverse pregnancy outcomes (i.e. presence/absence of HDP, LGA, and/or neonatal hypoglycemia), and their interaction as fixed effects. In 87 gravidas with preconception median hemoglobin A1c 6.5% (IQR 6.0, 7.1) and maternal body mass index 24.8 kg/m2 (IQR 21.9, 27.1), 71% had at least one adverse pregnancy outcome. Between weeks 240 and 376, gravidas with HDP had higher TAR and mean glucose and lower TIR (P < .05). Gravidas with LGA had lower TBR between weeks 240 and 356. TIR, TAR, and mean glucose evolution differed by HDP status, with greatest divergence between groups at 280 to 296 weeks' gestation (P ≤ .001). CGM metrics in the late second to early third trimester, a period of peak insulin resistance, may help to distinguish risk of HDP and LGA in gravidas with T1DM.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently gained prominence as both anti-diabetic medications and treatments for obesity in pregnancy. Nevertheless, the safety profile concerning maternal and fetal outcomes remains inadequately investigated. This meta-analysis examines the safety of GLP-1 RA utilization in pregnant women, providing valuable insights into maternal and fetal outcomes. Methods: Per PRISMA guidelines, a comprehensive literature search was performed in PubMed, Google Scholar, and Embase, along with snowballing to identify relevant studies reporting adverse maternal or fetal outcomes in pregnant women who used GLP-1 RA or other anti-diabetic medications either preconceptionally or periconceptionally. Maternal outcomes included hypertensive disorders of pregnancy, gestational diabetes, cesarean delivery, and pregnancy loss. Fetal outcomes included preterm birth, major congenital anomalies, and abnormal birth weight. Binary random-effects models were utilized to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). A p-value &lt;0.05 was considered statistically significant. Results: Four studies with 36,963 pregnancies were analyzed. GLP-1 RA was significantly associated with reduced adverse maternal outcomes (OR: 0.72, 95% CI: 0.66-0.79, p &lt; 0.00001) and preterm birth (OR: 0.66, 95% CI: 0.53 - 0.82, p = 0.0001). However, no increased risk of major congenital anomalies was found compared to other medications (OR: 1.08, 95% CI: 0.86-1.37, p = 0.51) or insulin (OR: 1.00, 95% CI: 0.77-1.28, p = 0.98) (Fig 1). Although there was a noticeable trend toward reduced adverse fetal outcomes, the heterogeneity was significant. This variability is likely due to differences in baseline risk, timing of exposure, and how outcomes were defined in the various studies. Conclusion: GLP-1 RA use during pregnancy is associated with improved maternal outcomes and reduced preterm birth, without increased risk of congenital anomalies. Considering the cardiometabolic interplay between pregnancy complications and future cardiovascular disease, these findings support the necessity for future prospective cardio-obstetric studies aimed at assessing the long-term cardiovascular risks for both mothers and their offspring following GLP-1 RA exposure.

Introduction/ Background: Lifelong continuity of care is essential for individuals with congenital heart disease (CHD). Despite guidelines recommending uninterrupted follow-up, gaps in care (GIC) remain common and are associated with adverse health outcomes. The underlying factors contributing to GIC are not well understood. Machine learning offers a novel approach to identify at-risk populations and understand predictors of GIC. Research Questions/Hypothesis: We aimed to develop and evaluate a machine learning model to predict which CHD patients are most at risk for GIC and to identify key social determinants of health demographics and clinical features contributing to GIC. Methods: /Approach: In this retrospective cohort study, we analyzed 1,948 CHD patients aged 0–34 years who underwent surgery at a multi-state pediatric subspecialty center from 2003-2020. A GIC was defined as a &gt;3 year lapse between cardiology visits. Patients were categorized as GIC (n=274) or without GIC (n=1674). Demographics and SDOH, including race, ethnicity, sex, language, and Child Opportunity Index (COI) by ZIP code, were incorporated into the model. A Random Forest classifier was trained on a 70:30 split dataset using Synthetic Minority Over-sampling Technique to address class imbalance. Model optimization involved hyperparameter tuning via GridSearchCV and was evaluated using ROC, feature importance, and F1 score. Results/Data: The model demonstrated good overall performance, with an AUC of 0.728. Among patients without GIC, the model showed strong precision (0.88), recall (0.93), and F1 score (0.90), highlighting its ability to correctly identify those maintaining follow-up. While performance was more limited in predicting GIC (F1 score: 0.23), the model provides a foundational step toward improving predictive accuracy in this group. Key features influencing follow-up status included time since last visit, anatomic complexity, age &gt;10.5 years, greater distance to care, and white non-Hispanic race/ethnicity (Figures 1–3). Conclusion: This study highlights the potential of machine learning to proactively identify CHD patients at risk for GIC. Though additional training is needed to optimize predictions for the GIC group, current findings demonstrate moderate to high accuracy in identifying patients who maintain care. These insights can inform targeted strategies based on clinical and social risk factors to reduce GIC and improve long-term outcomes.

Introduction: Food insecurity, a critical social determinant of health, that affects many women of reproductive age, particularly those living in communities at high risk for cardiovascular disease and adverse pregnancy outcomes. While food insecurity is linked to poor cardiometabolic health, few studies have examined its impact among a diverse population of reproductive-age women using cardiovascular health metrics like Life’s Essential 8 (LE8). Methods: We conducted a cross-sectional analysis of women aged 18–50 enrolled in the SAFE HEART Study, which includes participants recruited through community outreach and the American Heart Association’s Research Goes Red registry. Food insecurity was assessed using a validated two-item screener. Key Cardiovascular health measures including sleep, BMI, cholesterol, blood glucose, and blood pressure. Multivariable logistic regressions estimated odds ratios (ORs) and 95% confidence intervals (CIs) for adverse LE8 outcomes associated with food insecurity across three models: unadjusted, sociodemographic-adjusted, and fully adjusted for cardiovascular risk factors. Results: Among 430 participants (mean age: 30.7 ± 6.8), 44.7% were Non-Hispanic Black, 28.1% Hispanic/Other, and 23.0% Non-Hispanic White. Food insecurity was significantly associated with adverse LE8 risk factors. In fully adjusted models, women who reported being worried food would run out (Question 1) had higher odds of high cholesterol (OR = 2.83; 95% CI: 1.45–5.54), diabetes (OR = 1.98; 95% CI: 1.01–3.88), and poor sleep (OR = 1.61; 95% CI: 1.01–2.57). Women who reported food did not last (Question 2) also had increased odds of high cholesterol (OR = 2.04; 95% CI: 1.06–3.91) and diabetes (OR = 1.99; 95% CI: 1.03–3.84). Other LE8 risk factors were not significantly associated with food insecurity in fully adjusted models. Conclusion: Food insecurity was independently associated with adverse LE8 cardiovascular health risk factors, specifically high cholesterol, diabetes, and poor sleep, among women of reproductive age. These findings highlight food insecurity as a modifiable risk factor and reinforce the importance of integrating social risk screening and intervention into CVD prevention efforts targeting diverse populations.

Background: Diabetes mellitus is a known risk factor for adverse cardiovascular outcomes, particularly in patients with atrial fibrillation. While left atrial appendage occlusion (LAAO) has emerged as a viable alternative to long-term anticoagulation, the influence of glycemic control on post-procedural outcomes remains inadequately defined. This study aimed to evaluate cardiovascular outcomes among nondiabetic (NDM), well-controlled diabetic (WCDM; HbA1c &lt;7%), and poorly controlled diabetic (PCDM; HbA1c ≥7%) patients undergoing LAAO. Research Question: Does diabetes and its glycemic control status affect adverse cardiovascular outcomes following LAAO in atrial fibrillation patients? Methods: Using the TriNetX Global Collaborative Network, we identified adult AF patients who underwent LAAO between 2018 and 2024. Patients were stratified into three comparisons: Diabetics vs NDM, WCDM vs NDM, and PCDM vs NDM. Propensity score matching (PSM) was employed to balance 26 baseline covariates across cohorts. Outcomes including major adverse cardiovascular events (MACE), stroke and all-cause mortality were assessed over a 5-year follow-up. Risk analysis and Kaplan-Meier survival curves were used to derive hazard ratios (HR) and 95% confidence intervals (CI). Results: In the overall analysis, major adverse cardiovascular events (MACE) occurred in 13.4% of diabetics versus 9.0% of non-diabetics (HR, 1.44; 95% CI, 1.28–1.62) and all-cause mortality in 15.2% versus 12.3% (HR, 1.15; 95% CI, 1.05–1.25). Stroke occurred in 5.1% versus 3.6% (HR, 1.30; 95% CI, 1.09–1.54), pulmonary embolism in 2.8% versus 2.1% (HR, 1.25; 95% CI, 1.02–1.54), and ventricular fibrillation in 1.0% versus 0.5% (HR, 1.81; 95% CI, 1.22–2.70). In the HbA1c &gt;7% subgroup, MACE risk was further elevated (HR, 1.59; 95% CI, 1.25–2.00), whereas diabetics with HbA1c &lt;7% still experienced increased risk (HR, 1.39; 95% CI, 1.21–1.60) compared with non-diabetics. Conclusion: Poor glycemic control (HbA1c ≥7%) in diabetic patients with atrial fibrillation undergoing LAAO is associated with a significantly increased long-term risk of MACE, stroke, and mortality. Notably, both suboptimal and even controlled glycemic states appear to confer elevated cardiovascular risk, underscoring the complex interplay between diabetes and outcomes post-LAAO. These findings highlight the critical importance of individualized glycemic management and comprehensive cardiovascular risk reduction strategies in this high-risk population.