Key Points:

• Standard cardiology practice recommends aspirin monotherapy indefinitely after DAPT for prevention of cardiovascular events after PCI, but some data has suggested clopidogrel therapy may be a superior alternative
• The SMART-CHOICE 3 trial is the first large multicenter trial to evaluate clopidogrel versus aspirin monotherapy among 5000 patients in 26 sites across South Korea
• The study found a significant improvement in major adverse cardiovascular and cerebrovascular outcomes among clopidogrel versus aspirin with no significant increase in bleeding
• This trial has ramifications for chronic coronary disease management in high risk ischemic patients after standard DAPT post-PCI

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Key Points:

• The FAME 3 trial tested whether percutaneous coronary intervention (PCI) could offer comparable long-term outcomes to coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease by limiting intervention to flow-limiting lesions as determined by fractional flow reserve (FFR)
• Among 1,500 patients, FFR-guided PCI as compared to CABG had similar death and stroke rates but PCI resulted in higher rates of myocardial infarction and repeat revascularization.
• These findings support shared decision-making in selecting revascularization strategies, highlighting the evolution of PCI outcomes in contemporary practice.

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Key Points:

• This study presents updated national data from the Race Associated Cardiac Event Registry (RACER) on cardiac arrest incidence and outcomes during long-distance running races in the United States between 2010 and 2023.
• Among over 29 million race finishers, cardiac arrest occurred at a rate of 0.60 per 100,000 finishers, with significantly higher rates in men (1.12 per 100,000) compared to women (0.19 per 100,000) and marathon participants (1.04 per 100,000) versus half-marathoners (0.47 per 100,000). The overall survival to hospital discharge improved to 66% during this period, a marked increase from earlier data.
• Although cardiac arrest during long-distance running races remains exceedingly rare, enhanced emergency preparedness—particularly rapid CPR and defibrillation—has significantly improved outcomes.

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Key Points:

• Prior trials have demonstrated limited benefit to intra-aortic balloon pump (IABP) use in acute myocardial infarction-related cardiogenic shock, but the role of IABP in heart failure-related cardiogenic shock (HF-CS) is not yet clear.
• The ALTSHOCK2 trial was designed to examine the utility of early IABP implantation in improving the primary endpoint of 60-day survival or bridge to heart replacement therapy (HRT) in HF-CS.
• There was no difference in the primary endpoint between early IABP and standard of care treatment.

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Key Points:

• While fluid restriction is a standard recommendation for patients with chronic heart failure (HF), there is limited evidence to support its use.
• The FRESH-UP trial was designed to examine the utility of fluid restriction vs liberal fluid intake in individuals with NYHA II or III chronic HF.
• There was no difference in symptom burden or safety events between the liberal fluid intake and fluid restriction groups, with an increase in thirst distress in the fluid restriction group. 

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Key Takeaways:

1. Elevated baseline NT-proBNP and hs-cTnT levels were associated with higher cardiovascular event rates, but did not predict greater relative benefit from early TAVR compared to clinical surveillance.
2. The EARLY TAVR trial supports early intervention across the spectrum of biomarker concentrations in asymptomatic severe AS.

This pre-specified biomarker analysis of the EARLY TAVR trial (NCT03042104), presented at the American College of Cardiology Annual Scientific Session (ACC.25) and published simultaneously in Circulation, evaluated the role of baseline cardiac biomarkers—N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT)—in guiding the timing of transcatheter aortic valve replacement (TAVR) in asymptomatic patients with severe aortic stenosis (AS). Although elevated biomarker levels were associated with increased cardiovascular risk, they demonstrated limited utility in identifying patients who derived greater relative benefit from early TAVR compared to clinical surveillance.

This secondary analysis involved 798 patients randomized to early TAVR (n=398) or clinical surveillance (n=400). Patients were stratified by baseline NT-proBNP and hs-cTnT levels. Higher baseline levels of NT-proBNP (>median, 222 pg/mL) and elevated hs-cTnT (>15 ng/L) were significantly associated with increased risk of death or heart failure hospitalization at two years: NT-proBNP >222 pg/mL (hazard ratio [HR] 2.96; 95% CI, 1.87–4.69; p<0.001) and hs-cTnT >15 ng/L (HR 3.27; 95% CI, 2.04–5.24; p<0.001).

However, early TAVR provided similar or greater relative benefit compared to surveillance irrespective of baseline biomarker status. For patients with NT-proBNP ≤222 pg/mL, early TAVR significantly reduced the composite endpoint of death, stroke, or unplanned cardiovascular hospitalization compared to surveillance (HR 0.39; 95% CI, 0.23–0.64; p<0.001). Among patients with NT-proBNP >222 pg/mL, early TAVR also showed benefit but to a lesser degree (HR 0.71; 95% CI, 0.50–1.00; p=0.05; interaction p=0.06). Similarly, in patients with normal hs-cTnT levels (≤15 ng/L), early TAVR markedly reduced the composite endpoint compared with surveillance (HR 0.45; 95% CI, 0.29–0.69; p<0.001). Among patients with elevated hs-cTnT (>15 ng/L), the benefit was attenuated (HR 0.66; 95% CI, 0.44–0.98; p=0.04), with significant interaction (interaction p=0.04), indicating a greater relative benefit of early TAVR among patients with normal cardiac troponin.

Absolute risk reductions, however, were numerically larger among patients with higher baseline biomarkers due to higher overall event rates. Despite these differences, early TAVR consistently showed benefit across all biomarker levels, challenging guideline recommendations emphasizing biomarker thresholds to guide intervention timing.

Lead investigator Dr. Brian Lindman emphasized, “Our findings suggest limited value for single measurements of biomarkers to guide the timing of TAVR in asymptomatic patients. While biomarkers reflect higher risk, the relative benefit of early intervention appears consistent across biomarker levels.”

Key Takeaways:

1. Intramyocardial autologous bone marrow cell therapy was safe in patients with ischemic HFrEF but did not meet its primary efficacy outcome using the 6-minute walk test.
2. Exploratory analyses indicated meaningful clinical improvements, particularly in patients with higher baseline NT-proBNP levels, highlighting a potentially beneficial role for targeted cell therapy in this subgroup.

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Key Takeaways:

1. SHR-1918, an ANGPTL3 inhibitor, significantly reduced LDL cholesterol by approximately 22–30% and triglycerides by 52–63% in patients with ASCVD not optimally controlled by standard lipid-lowering therapy.
2. The safety profile of SHR-1918 was favorable, with predominantly mild adverse events comparable to placebo, suggesting strong potential for clinical application to address residual cardiovascular risk.

In a multicenter, randomized, double-blind, placebo-controlled Phase 2 trial (NCT06109831), the novel angiopoietin-like 3 (ANGPTL3) monoclonal antibody SHR-1918 demonstrated significant reductions in LDL cholesterol (LDL-C) and triglycerides (TG) in patients with moderate or higher risk atherosclerotic cardiovascular disease (ASCVD) whose lipid levels remained suboptimal despite standard lipid-lowering therapies. The findings, presented at the American College of Cardiology Annual Scientific Session (ACC.25) and simultaneously published in the Journal of the American College of Cardiology, underscore the potential for ANGPTL3 inhibition as a potential therapeutic strategy to reduce residual cardiovascular risk.

The study enrolled 333 participants in 35 medical centers in China who had not achieved optimal LDL-C control despite receiving statins (99.1% of participants) and other lipid-lowering therapies such as cholesterol absorption inhibitors (12.0%) or PCSK9 inhibitors (0.9%). Patients were randomized to receive subcutaneous SHR-1918 (150 mg, 300 mg, or 600 mg every 4 weeks [Q4W], or 600 mg every 8 weeks [Q8W]) or placebo for 16 weeks, followed by an extended open-label phase lasting up to 56 weeks.

At week 16, SHR-1918 produced dose-dependent and statistically significant reductions in LDL-C compared with placebo, achieving reductions of 21.7% (150 mg Q4W), 27.3% (300 mg Q4W), 29.9% (600 mg Q4W), and 22.5% (600 mg Q8W) (all p<0.0001). Significant triglyceride reductions were also observed, ranging from 51.7% to 63.2% across SHR-1918 dosing groups (all P<0.0001). The percentage of patients achieving LDL-C targets at week 16 ranged from 59.1% to 71.2% in the SHR-1918 groups, significantly higher than placebo (approximately 31%).

Safety analyses indicated SHR-1918 was well tolerated, with adverse event rates comparable between treatment groups and placebo. Treatment-related adverse events were predominantly mild and occurred infrequently. The most common treatment-related events included injection-site reactions (3.4%), hyperuricemia (2.6%), and mild elevations in creatine phosphokinase and liver enzymes, none of which were associated with long-term safety concerns.

Dr. Xiaojie Xe and Dr. Jian’an Wang, the lead investigators of the study wrote, “The core advantage of SHR-1918 lies in its unique target of action by inhibiting ANGPTL-3 while enhancing the activity of LPL and EL, which achieves dual regulation of LDL-C and TG. The findings of this study support that SHR-1918 could be a novel treatment option for patients with moderate or higher risk of ASCVD who have not achieved optimal lipid control and need additional lipid reduction beyond statins and other lipid-lowering therapies. 

Further research, including larger Phase 3 studies, will be essential to fully establish the clinical efficacy and long-term safety of SHR-1918.

Key Takeaways:

1. A deep learning ECG model significantly outperforms clinician interpretation in rapidly identifying patients who require coronary revascularization and accurately diagnosing type 1 myocardial infarction, performing comparably to high-sensitivity cardiac troponin assays.
2. The AI-based tool offers rapid risk stratification in emergency departments, potentially reducing treatment delays and improving clinical outcomes, especially for patients without obvious ST-segment elevations on initial ECGs.

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Key Points:

• In a randomized crossover study, authors assessed whether artificial intelligence (AI) can improve accuracy of cardiologists when evaluating echocardiograms for severe aortic stenosis (AS).
• While diagnostic sensitivity did not statistically improve, AI demonstrated perfect classification of severe AS and significantly reduced inter-reader variability and time to complete interpretations.
• The study highlights opportunities and barriers in integrating AI into clinical workflows.

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Key Points:

• Obesity increases the risk of atrial fibrillation (AF) by 19–29% for every 5-unit increase in BMI. While catheter ablation has been more effective than antiarrhythmic drugs (AADs), the impact of lifestyle changes combined with AADs had not been thoroughly tested against catheter ablation.
• The PRAGUE-25 trial compared catheter ablation to lifestyle modification, including weight loss, combined with AADs in obese patients with AF.
• At 12 months, freedom from AF was significantly higher with catheter ablation (73.0%) than with lifestyle changes and AADs (34.6%).
• Despite improvements in metabolic health and physical fitness, lifestyle changes with AADs were not as effective as ablation in maintaining normal heart rhythm.

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Key Points:

• Pulmonary arterial hypertension (PAH) is a progressive disease with poor outcomes despite advancements in therapy.
• Sotatercept, a novel activin signaling inhibitor, targets vascular remodeling in PAH and has previously demonstrated efficacy in improving hemodynamics and clinical outcomes.
• The Phase 3 ZENITH trial showed that sotatercept significantly reduced the risk of composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension by 76% compared to placebo in high-risk PAH patients (WHO FC III/IV) on maximum tolerated background therapy.

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Key Points

• The SUMMIT randomized control trial demonstrated that tirzepatide significantly reduced worsening heart failure events among patients with HFpEF and obesity compared to placebo. 
• This secondary analysis focused on the 60% of SUMMIT patients with the triad of HFpEF, obesity, and CKD, as they represent a population of patients with cardiovascular-kidney-metabolic syndrome, an especially high-risk group.
• The relative benefits of tirzepatide were the same amongst those with and without CKD, indicating that baseline eGFR did not influence the magnitude of the relative risk reduction in major adverse heart failure outcomes from tirzepatide. The absolute risk reduction was numerically greater among those with CKD.
• At one year tirzepatide was associated with an improvement in eGFR in all patients when assessed using cystatin C, but only those with CKD when estimated by serum creatinine; though these measurements may be confounded by the effect of the treatment on fat and muscle mass. Albuminuria also improved similarly for patients with and without CKD. 

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Key Points

• The COLCOT trial demonstrated colchicine improved coronary plaque characteristics in patients with acute coronary syndrome compared with placebo. EKSTROM sought to determine whether colchicine would reduce plaque progression in patients with stable CAD  compared to placebo, as measured by coronary CTA (CCTA).
• EKSTROM randomized 84 patients with proven coronary atherosclerosis to colchicine 0.5mg or placebo. Baseline CCTA were compared with followup CCTA at 1 year. The primary endpoint was a change low attenuation plaque volume; secondary endpoints included changes in total plaque volume and other plaque characteristics. 
• There was no significant difference in the rate of change of low attenuation plaque, however colchicine was associated with a significant 1.1% reduction in total plaque volume progression and also significantly slowed dense calcium progression at one year.
• This pilot study provides justification for further investigation of the impact of anti-inflammatory therapies on coronary plaque characteristics over time. 

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Key Points

• The DECODE-CKD trial investigated the effects of SGLT-2 inhibitor Dapagliflozin on cardiac structure and function in patients with chronic kidney disease (CKD).
• A double blinded, single centered, investigator initiated, placebo controlled randomized trial assessed cardiac structure and function in 222 patients over a period of 6 months. 
• A significant reduction in the left ventricular mass index (LVMi) was noticed after 6 months of therapy, and consistent in all subgroups. A concomitant proportional dip in the estimated glomerular filtration rate (eGFR) was also noted. 

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Key Points

• The ESPRIT trial assessed whether the efficacy and safety of intensive blood pressure (BP) varies across frailty status compared to control.
• In this open-label trial, 11,255 patients were randomized into intensive vs standard blood pressure treatment groups. Both groups were followed over a median of 3.4 years.
• The findings support the adoption of intensive blood pressure control, targeting a systolic BP below 120 mmHg, in hypertensive patients at high cardiovascular risk, regardless of frailty status.

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Key Points: 

• In this sub analysis of the EARLY TAVR trial, the authors aim to evaluate outcomes among all patients who underwent transcatheter aortic valve replacement (TAVR), regardless of whether they were randomized to receive early TAVR versus clinical surveillance.
• Patients who underwent delayed AVR had higher rates of periprocedural stroke (1.8% vs. 0.9%) and permanent pacemaker implantation (8.4% vs. 5.7%).
• There were significant differences in the rates of the primary outcome (death, stroke, and unplanned hospitalizations for cardiovascular causes) between the delayed AVR with acute valve syndrome vs. delayed TAVR with progressive valve syndrome vs. early TAVR group with a rate of 14.9% vs. 8.2% vs. 6.8% respectively (log rank: p=0.008).  

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Key Points: 

• In the ARISE-ARMYDA 7 trial, 40 patients who presented with ST elevation myocardial infarction and a plan for a deferred stenting strategy were randomized to receive rivaroxaban 2.5 mg + dual-antiplatelet therapy (DAPT) or DAPT alone to evaluate the primary endpoint of OCT-derived thrombus burden reduction after six days.
• There was a significantly greater reduction in OCT-derived thrombus burden after 6 days in the rivaroxaban + DAPT group compared to the DAPT alone group.

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Key Points:

• Many patients with ASCVD are on LDL-lowering therapy, but many patients with elevated TGs remain at elevated risk
• Solbinsiran, a novel siRNA therapy, may lower cholesterol by targeting hepatic ANGPTL3 and thereby increasing hepatic clearance of triglyceride lipoprotein components
• This trial demonstrated solbinsiran 400mg had significant reduction in apoB, ANGPTL3, hepatic fat, and other cholesterol markers
• Given a favorable safety profile, though limitations are noted, the trial suggests investigation of targeting hepatic ANGPTL3 reduction in mixed hyperlipidemia patients at high ASCVD risk

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Key Points:

• Health360x.ai is an AI-powered digital health platform designed to scale access to decentralized clinical trials (DCTs) by addressing infrastructure gaps in small and medium-sized practices.
• Across 35 community-based sites, the registry enrolled 7,513 participants: 85% Black, 8% White, 58% female, and 15% from rural areas. Over half (51%) reported annual income <$25,000.
• High adoption metrics included a 95% usability score and strong engagement with chatbot tools and site team training (p<0.02 vs baseline).

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