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Background In low-gradient severe aortic stenosis (AS), reduced left ventricular ejection fraction (LVEF <50%) is practically used to define low flow and prompt dobutamine stress echocardiography to discern pseudo-severe AS. In patients with preserved LVEF, stroke volume index (SVI) <35 mL/m² is typically used. However, both are volume-based surrogates. Transaortic flow rate (TAFR), calculated as stroke volume divided by left ventricular ejection time, may better reflect true flow. Nonetheless, comparative data between TAFR and established metrics remain limited. We aimed to evaluate the prognostic value of TAFR in symptomatic low-gradient severe AS. Methods We retrospectively identified patients with low-gradient severe AS (AVA ≤1 cm 2 and peak velocity (Vmax) <4 m/s or mean gradient (MG) <40 mm Hg) who underwent transcatheter aortic valve replacement at Mayo Clinic sites (2017–2023). The primary outcome was 1-year all-cause mortality. Survival was assessed using Kaplan-Meier and Cox proportional hazards models. Results Among 475 patients included (mean age 85±8 years; 49% women), 242 (51%) had TAFR <220 mL/s, 165 (35%) had EF <50%, and 221 (47%) had SVI <35 mL/m 2 . Low TAFR was significantly associated with higher 1-year mortality even after stratifying by EF or SVI. In multivariate analysis, TAFR was an independent predictor of mortality (HR 2.38; 95% CI 1.19 to 4.76, p=0.014) after adjusting for reduced LVEF, low SVI, gender, chronic kidney disease and mitral and tricuspid regurgitation. Conclusions In patients with symptomatic low-gradient severe AS, low TAFR, not SVI or LVEF, is independently associated with mortality and may offer more accurate measure of flow state for clinical staging.

Abstract Aims Obesity is linked with worse outcomes in hypertrophic cardiomyopathy (HCM). While both bariatric surgery (BS) and GLP-1 receptor agonists (GLP-1RA) promote weight loss and may improve cardiometabolic risk, their comparative outcomes in HCM remain unclear. Methods and results Adults with HCM and body mass index (BMI) ≥ 30 kg/m were divided into two cohorts: (i) GLP-1 RA users who never had BS, and (ii) BS patients who never received GLP-1 RA. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and medications. Outcomes over 24 months include all-cause mortality, acute heart failure (HF) hospitalization, arrhythmias, change in BMI, and cardiovascular symptoms. Hazard ratios with 95% confidence intervals were estimated using Cox models. Of 5002 patients, 955 were included in each matched cohort after matching (mean age 54 ± 13 years, 70% female, BMI 40.0 kg/m). GLP-1 RA was associated with a significantly lower observed rate of all-cause mortality compared with BS (2.0% vs. 4.4%; HR 0.46; 95% CI 0.27–0.80; P = 0.004) and HF hospitalization (8.7% vs. 14.0%; HR 0.60; 95% CI 0.46–0.79; P &lt; 0.001). Similarly, GLP-1 RA use was associated with a lower incidence of composite cardiovascular outcomes (10.7% vs. 17.2%; HR 0.60; 95% CI 0.47–0.77; P &lt; 0.001). Rates of arrhythmia and cardiovascular symptoms were comparable between the two groups. BMI reduction was greater after bariatric surgery (−4.0 vs. −2.6 kg/m; P &lt; 0.001). Conclusion In obese patients with HCM, GLP-1 RA therapy was associated with lower all-cause mortality and fewer HF events compared with BS. Future studies are warranted to confirm our findings.

Abstract Background/Introduction Acute coronary syndrome (ACS) is common among elderly patients and is associated with a high risk of complications. Managing ACS, particularly dual antiplatelet therapy (DAPT), poses challenges due to the increased risk of recurrent hemorrhagic and ischemic events in this population. Purpose This study evaluated cardiovascular outcomes in patients ≥75 years that were initiated on DAPT with aspirin (ASA) plus either ticagrelor or clopidogrel following an acute myocardial infarction (AMI). Methods We used the TriNetX repository to identify adult patients (≥75 years) diagnosed with AMI between January 1, 2011, and December 31, 2021, who subsequently initiated DAPT and were not on anticoagulation. Patients were stratified into two cohorts: ASA + ticagrelor and ASA + clopidogrel. Outcomes assessed included major bleeding, repeat coronary intervention, all-cause mortality, all-cause hospitalizations, stroke, new-onset atrial fibrillation, and pacemaker implantation. Follow-up time was restricted to one year. A 1:1 propensity score matching algorithm was applied using the greedy nearest-neighbor method with a caliper of 0.1 pooled standard deviations to ensure balance (i.e., comorbidities, medications, laboratory values) between the two cohorts. Logistic regression models were used to calculate adjusted odds ratios (aOR), and Cox proportional hazards models estimated hazard ratios (HR). Results Before propensity score matching (PSM), 19,859 patients were in the ASA + ticagrelor cohort, and 47,032 were in the ASA + clopidogrel cohort. Post-PSM, 19,746 patients remained in each cohort, with a mean age of 82.2 years and a mean follow-up duration of 298.77 days for the ASA + ticagrelor cohort and 297.59 days for the ASA + clopidogrel cohort. The ASA + ticagrelor cohort had a higher incidence of major bleeding (aOR 1.19 [95% CI, 1.08–1.31]) and pacemaker implantation (aOR 1.14 [95% CI, 1.02–1.29]) compared to the ASA + clopidogrel cohort. Event-free survival analysis showed lower survival rates for major bleeding (HR 1.18 [95% CI, 1.07–1.30]) and pacemaker implantation (HR 1.14 [95% CI, 1.01–1.28]). No significant differences were observed between cohorts in repeat coronary interventions (aOR 0.95 [95% CI, 0.88–1.03]), atrial fibrillation (aOR 1.03 [95% CI, 0.97–1.08]), all-cause mortality (aOR 1.03 [95% CI, 0.96–1.12]), all-cause hospitalization (aOR 1.01 [95% CI, 0.97–1.05]), or stroke (aOR 0.95 [95% CI, 0.86–1.04]). Conclusions In elderly patients, DAPT with ASA + ticagrelor was associated with higher rates of major bleeding and need for pacemaker compared to ASA + clopidogrel. Given the similar risks of recurrent coronary intervention and mortality between the two regimens, these findings highlight the need for careful consideration when selecting ticagrelor over clopidogrel in this population.

Coronary artery disease (CAD) remains the leading cause of cardiovascular morbidity and mortality worldwide, with plaque composition and morphology being as key determinants of disease progression and clinical outcomes. Accurate plaque characterization is essential for risk stratification and therapeutic decision-making, yet conventional image interpretation is limited by inter-observer variability and time-intensive workflows. Artificial intelligence (AI) models have emerged as a transformative tool for automated coronary plaque analysis across multiple imaging modalities. AI-driven models demonstrate high diagnostic accuracy for plaque detection, segmentation, quantification, and vulnerability assessment. Integration of AI-derived imaging biomarkers with clinical risk scores can further enhance prediction of major adverse cardiovascular events and supports personalized management. These advances position AI-enhanced imaging as a powerful adjunct for both invasive and non-invasive evaluation of CAD. Despite its promise, important barriers to widespread clinical adoption remain, including data heterogeneity, algorithmic bias, limited model transparency, insufficient prospective validation, regulatory challenges, and incomplete integration into clinical workflows. Addressing these challenges will be essential to ensure safe, generalizable, and cost-effective implementation of AI in routine cardiovascular care.

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.

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.

Advances in plaque imaging have transformed cardiovascular diagnostics through detailed characterization of atherosclerotic plaques beyond traditional stenosis assessment. This review outlines the clinical applications of varying modalities, including dual-layer spectral CT, photon-counting CT, dual-energy CT, and CT-derived fractional flow reserve (CT-FFR). These technologies offer improved spatial resolution, tissue differentiation, and functional assessment of coronary lesions. Additionally, artificial intelligence has emerged as a powerful tool to automate plaque detection, quantify burden, and refine risk prediction. Collectively, these innovations provide a more comprehensive approach to coronary artery disease evaluation and support personalized management strategies.