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Daily Cardiology Research Analysis

3 papers

Three impactful cardiology studies stand out today: a large RCT shows clopidogrel monotherapy outperforms aspirin after standard DAPT in high‑risk post‑PCI patients; a multicenter noninferiority RCT demonstrates angiography‑derived FFR guidance is noninferior to intravascular ultrasound for comprehensive PCI strategy; and a deep‑learning CMR study of 60,000+ individuals proposes a new population threshold for “mild aortic stenosis,” validated in a 365,000‑patient echo cohort, with prognostic rel

Summary

Three impactful cardiology studies stand out today: a large RCT shows clopidogrel monotherapy outperforms aspirin after standard DAPT in high‑risk post‑PCI patients; a multicenter noninferiority RCT demonstrates angiography‑derived FFR guidance is noninferior to intravascular ultrasound for comprehensive PCI strategy; and a deep‑learning CMR study of 60,000+ individuals proposes a new population threshold for “mild aortic stenosis,” validated in a 365,000‑patient echo cohort, with prognostic relevance.

Research Themes

  • Antithrombotic therapy optimization after PCI
  • Imaging-driven procedural guidance in coronary intervention
  • AI-enabled population thresholds redefining valvular disease

Selected Articles

1. New Threshold for Defining Mild Aortic Stenosis Derived From Velocity-Encoded MRI in 60,000 Individuals.

88Level IICohortJournal of the American College of Cardiology · 2025PMID: 40175013

Using velocity-encoded CMR and deep learning in 62,902 participants, the authors derived population reference ranges for aortic valve hemodynamics and identified a “mild AS” threshold (>95th percentile) that separates normal from abnormal function. This threshold was prognostically adverse and externally validated in 365,870 people from NEDA, supporting a data-driven redefinition of mild AS.

Impact: This work proposes a robust, externally validated, population-based threshold for mild AS with prognostic value, potentially reshaping screening, follow-up, and clinical definitions.

Clinical Implications: Clinicians may consider earlier surveillance for patients exceeding the data-driven ‘mild AS’ thresholds and integrate AI-derived CMR or validated echo surrogates into risk stratification, while awaiting guideline updates.

Key Findings

  • Deep learning quantified AV area, peak velocity, and mean gradient from velocity‑encoded CMR in 62,902 UK Biobank participants.
  • A natural boundary (>95th percentile) in AV hemodynamics was defined as ‘mild AS’ and associated with adverse outcomes.
  • External validation in 365,870 individuals from NEDA confirmed prognostic relevance and generalizability.

Methodological Strengths

  • Very large primary cohort with external validation in an independent, massive clinical database
  • Objective, automated hemodynamic quantification using deep learning on CMR

Limitations

  • Observational design with potential residual confounding
  • CMR-based thresholds may require translation and calibration to echocardiography in routine care

Future Directions: Prospective validation of risk-guided surveillance based on the new thresholds, harmonization with echocardiographic parameters, and assessment of intervention timing.

2. Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): a randomised, open-label, multicentre trial.

86.5Level IRCTLancet (London, England) · 2025PMID: 40174599

Among 5,506 high-risk post-PCI patients who had completed standard DAPT, clopidogrel monotherapy reduced the composite of death, MI, or stroke versus aspirin (3‑year KM 4.4% vs 6.6%; HR 0.71) without increasing bleeding (3.0% vs 3.0%). Benefits were consistent across components (notably lower MI) and achieved with similar dosing and tolerability.

Impact: Challenges the default practice of aspirin for chronic maintenance after PCI by demonstrating superior ischemic protection with clopidogrel without excess bleeding in high-risk patients.

Clinical Implications: For high-risk patients post-PCI who have completed guideline‑recommended DAPT, clopidogrel monotherapy can be considered over aspirin to reduce death/MI/stroke without added bleeding; implementation should consider local genotypes/drug interactions and guideline updates.

Key Findings

  • Primary composite endpoint lower with clopidogrel vs aspirin (3‑year 4.4% vs 6.6%; HR 0.71, p=0.013).
  • No difference in major bleeding between clopidogrel and aspirin (3.0% vs 3.0% at 3 years).
  • Reductions observed in MI (HR 0.54) with similar dosing and tolerability across groups.

Methodological Strengths

  • Large, multicenter randomized trial with intention‑to‑treat analysis
  • Clinically meaningful, hard composite endpoints and adequate follow‑up

Limitations

  • Open-label design may introduce performance bias
  • Single‑country (South Korea) limits generalizability and pharmacogenomic diversity

Future Directions: Head-to-head comparisons in broader populations, genotype-guided antiplatelet strategies, and cost‑effectiveness analyses to inform global guidelines.

3. Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): a multicentre, randomised, non-inferiority trial.

85Level IRCTLancet (London, England) · 2025PMID: 40174597

In 1,839 randomized patients with significant CAD lesions eligible for both strategies, angiography‑derived FFR guidance was noninferior to IVUS guidance for the 12‑month composite of death/MI/revascularization (6.3% vs 6.0%; absolute difference 0.2 pp, upper 97.5% CI 2.4). The FFR strategy was associated with a lower proportion of vessels undergoing revascularization (69.5% vs 81.0%).

Impact: Demonstrates that a wire- and IVUS-sparing, physiology‑based, angiography‑derived FFR strategy can match IVUS for 12‑month outcomes while reducing revascularization, informing procedure planning and resource use.

Clinical Implications: Angiography‑derived FFR can be adopted as a comprehensive PCI guidance tool (decision and optimization) when IVUS is not available or to streamline procedures, with awareness of local expertise and patient selection.

Key Findings

  • Noninferiority for the 12‑month composite endpoint (death/MI/revascularization) between angiography‑derived FFR and IVUS guidance.
  • Lower proportion of target vessels revascularized in the angiography‑derived FFR arm (69.5% vs 81.0%).
  • Trial standardized decision and optimization criteria per arm; simultaneous dual‑modality use was prohibited.

Methodological Strengths

  • Multicenter randomized noninferiority design with prespecified PCI criteria and goals
  • Large sample, clinically relevant composite endpoint at 12 months

Limitations

  • Open-label design in a single-country setting (China) may limit generalizability
  • Noninferiority margin interpretation and operator technique variability

Future Directions: Head‑to‑head comparisons integrating cost‑effectiveness, patient‑reported outcomes, and long‑term durability; hybrid strategies and training standardization.