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Abstract Aims We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. Methods and results We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (≥18 years) with T2D who underwent TAVI (2015–2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 ± 1.1 and 2.6 ± 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583–0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706–0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749–0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677–0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719–0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510–0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. Conclusion In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits.

Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p<0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

Background: Glucagon-like peptide-1 (GLP-1) agonists have been shown to improve outcomes across various cardiovascular diseases. However, data regarding the effects of GLP-1 agonists in obstructive hypertrophic cardiomyopathy (HCM) is limited. Objective: This study aimed to evaluate the 5-year outcomes of GLP-1 agonists in patients with HCM. Methods: Using TriNetX Analytics Network, we identified patients aged ≥18 years with a diagnosis of obstructive hypertrophic cardiomyopathy between 1/1/2014 and 1/1/2019. Patients were divided into two groups: those treated with GLP-1 agonists for ≥ 1 year and those who were not. Propensity score matching (PSM) was performed using demographics, cardiac medications, and comorbidities. The study outcomes were 5-year all-cause mortality and cardiac adverse events. Results: A total of 52,978 patients with HCM were identified, including 2,654 (5.0%) patients treated with GLP-1 agonists. After PSM, 2,588 patients in each group were analyzed. Patients on GLP-1 agonists were associated with lower odds of all-cause mortality (5.0% vs. 15.6%, p<0.01), all-cause hospitalization (46.3% vs. 67.8%, p<0.01), acute decompensated heart failure ((9.4% vs. 21.4%, p<0.01), cardiac arrest (3.6% vs. 5.4%, p<0.01), cerebrovascular accidents (9.5% vs. 14.1%, p<0.01), and cardiogenic shock (1.4% vs. 3.6%, p<0.01). Additionally, reduced rates of new ICD implantation (3.5% vs. 7.9%, p<0.01) and septal reduction therapy (1.7% vs. 3.5%, p<0.01) were observed in the GLP-1 agonists group. Conclusion: The use of GLP-1 agonists in HCM was associated with improved cardiovascular outcomes. Future clinical trials are needed to validate these potential benefits.

Background: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome, particularly in young to middle-aged women. While most presentations are associated with preserved left ventricular ejection fraction (LVEF), a subset of patients present with acute systolic dysfunction. The characteristics of patients who recover their LVEF are not clearly defined. Methods: We retrospectively analyzed 495 patients with angiographically confirmed SCAD treated at three Mayo Clinic sites (Arizona, Rochester, and Florida) from 1994 to 2023. Patients with a prior history of myocardial infarction, coronary artery disease, and congenital heart disease were excluded. Baseline LVEF at SCAD presentation was categorized into <35%, 35–39%, 40–49%, and ≥50%. Follow-up LVEF was assessed by echocardiography performed between 30 days and 1 year post-SCAD. The primary outcome was improvement in LVEF to ≥50% at follow-up. Results: A total of 495 SCAD patients were included. At presentation, 26% had reduced LVEF: 6% had LVEF <35%, 5% had LVEF between 35–39%, and 15% had LVEF between 40–49%. Patients who did not normalize their EF at follow-up were slightly younger (45 vs. 48 years, p=0.04), were more likely to have had an in-hospital cardiac arrest (13% vs. 4%, p=0.01), required mechanical circulatory support during their care, and had SCAD involving the left main artery (11% vs. 2%, p=0.01). Predictors of EF normalization included SCAD which involved the obtuse marginals (15% vs. 4%, p<0.05). The group with the lowest EF at presentation had the highest probability of persistent EF <50% at follow-up (32% for those with LVEF <35%) while patients who had normal EF at presentation had a 6% chance of having EF <50% at follow-up (Figure 1). Conclusions: Our study shows that the majority of SCAD patients have normal EF at presentation. 80% of those with reduced EF at presentation will normalize at follow-up. Predictors of low EF at follow-up included dissection involving the left main artery, lower EF at SCAD presentation, in-hospital arrest and use of mechanical circulatory support.

Abstract Aims Left ventricular assist devices (LVADs) are a critical intervention for advanced heart failure (HF), serving as destination therapy or bridge to transplantation. Obesity and diabetes impact outcomes in patients with LVADs. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) demonstrate cardiovascular benefits; however, their role in patients with LVADs remains underexplored. We evaluated the association of GLP1-RA therapy with cardiovascular outcomes in patients with LVADs. Methods This retrospective cohort study used the TriNetX database, a research network database from 98 healthcare organizations. We queried for all adult LVAD recipients (≥18 years) and were stratified into GLP1-RA users and non-users. Propensity score matching (PSM) (1:1) balanced demographics, comorbidities, medication use and laboratory data. Outcomes included heart transplantation rates, heart failure hospitalizations, all-cause mortality, all-cause hospitalizations and cardiovascular events. Logistic regression models were used to estimate adjusted odds ratios (aOR). Results After PSM, we included a total of 1036 adult LVAD recipients (518 GLP1-RA users, 518 matched non-users) with a mean follow-up time of 311.6 ± 98.4 days for the GLP1-RA cohort and 304.0 ± 111.5 days for the non-GLP1-RAs cohort. Mean age was 56.7 ± 12.2 years in the GLP1-RA cohort and 58.0 ± 12.5 years in the non-GLP1-RA cohort. Females comprised 28.0% of both cohorts while White patients represented 52.1% of the GLP1-RA group and 53.1% of the non-GLP1-RA group. GLP1-RA users had higher heart transplantation rates [n = 98 (18.9%) vs. n = 44 (8.5%); aOR 2.514 (95% CI: 1.720–3.673)]. Acute HF events and all-cause hospitalizations were lower among GLP1-RA users compared with non-users [n = 288 (55.6%) vs. n = 357 (68.9%); aOR 0.565 (95% CI: 0.438–728) and n = 324 (62.5%) vs. n = 390 (75.3%); aOR 0.548 (95% CI: 0.420–0.716)]. No differences were observed when comparing the GLP1-RA cohort with the non-GLP1-RA cohort in regard to all-cause mortality [n = 32 (6.2%) vs. n = 44 (8.5%); aOR 0.709 (95% CI: 0.442–1.138)], stroke [n = 42 (8.1%) vs. n = 58 (11.2%); aOR 0.700 (95% CI: 0.461–1.062)] or cardiac arrest [n = 18 (3.5%) vs. n = 17 (3.3%); aOR 1.061 (95% CI: 0.541–2.082)]. Conclusions GLP1-RA therapy in patients with advanced HF and LVADs is potentially associated with improved heart transplantation rates while decreasing hospitalization and acute HF event rates.

Introduction: Sex-based differences in outcomes among patients with heart failure with reduced ejection fraction (HFrEF) treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. This study aimed to evaluate sex-specific differences in cardiovascular outcomes in patients with HFrEF receiving SGLT2 inhibitors alongside guidelinedirected medical therapy (GDMT). Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults with HFrEF treated with SGLT2is and GDMT were stratified by sex. Propensity score matching (PSM) was used to balance baseline demographics, comorbidities, medications, and laboratory data. Primary outcomes were all-cause mortality and acute heart failure (HF) events; secondary outcomes included hospitalizations, arrhythmias, renal outcomes, and advanced therapies. Results: After PSM, 17,408 male and 17,408 female patients were analyzed. Male patients had lower odds of acute HF events (aOR: 0.949; 95% CI: 0.909–0.991), all-cause hospitalizations (aOR: 0.933; 95% CI: 0.895–0.973), and renal failure (aOR: 0.915; 95% CI: 0.870–0.962). No significant differences were observed in all-cause mortality (aOR: 1.003; 95% CI: 0.926–1.087) or heart transplantation, although LVAD use was more frequent in males (aOR: 1.416; 95% CI: 1.053–1.905). Discussion: The findings highlighted potential sex-based disparities in outcomes for patients with HFrEF on SGLT2is. Differential prescribing patterns, comorbidity burden, or timing of therapy initiation may contribute to observed differences. Conclusion: Among HFrEF patients treated with SGLT2is, males experienced lower risks of HF events, hospitalizations, and renal failure compared to females, despite similar mortality. Further research is needed to understand and address sex-specific disparities in HFrEF management.