Weekly Cardiology Research Analysis
This week’s cardiology literature clustered around precision target discovery, randomized device and procedural strategies, and scalable diagnostic/ prevention innovations. Large multi-omics Mendelian-randomization work prioritized non-overlapping druggable targets for HFrEF versus HFpEF, offering a roadmap for subtype-specific therapeutics. Multiple randomized trials and meta-analyses clarified interventional choices (left-main bifurcation strategy, IVL vs RA for calcified PCI), antithrombotic
Summary
This week’s cardiology literature clustered around precision target discovery, randomized device and procedural strategies, and scalable diagnostic/ prevention innovations. Large multi-omics Mendelian-randomization work prioritized non-overlapping druggable targets for HFrEF versus HFpEF, offering a roadmap for subtype-specific therapeutics. Multiple randomized trials and meta-analyses clarified interventional choices (left-main bifurcation strategy, IVL vs RA for calcified PCI), antithrombotic regimens in AF+stable CAD, and expanded evidence for lipid‑lowering and mineralocorticoid receptor antagonism across ages. Applied AI, circulating circRNA biomarkers, and population-level salt‑substitution findings point to near-term diagnostic and public‑health implementation opportunities.
Selected Articles
1. Large-scale multi-omics identifies drug targets for heart failure with reduced and preserved ejection fraction.
Using Mendelian randomization across >420,000 discovery and >175,000 replication participants, the study identified 70 causal targets for HFrEF and 10 for HFpEF, largely non-overlapping, and prioritized druggable candidates (e.g., IL6R, ADM, EDNRA for HFrEF; LPA for both). The work integrates proteomic and transcriptomic data and provides systematic druggability profiling to guide subtype-specific therapeutic development.
Impact: Provides large-scale, genetically anchored target prioritization that reduces translational risk and directly informs trial and pipeline prioritization for HF subtypes.
Clinical Implications: Not yet practice-changing, but supplies a ranked list of causal, druggable targets to design subtype-specific interventional trials and companion biomarkers for HFrEF vs HFpEF.
Key Findings
- Identified 70 HFrEF and 10 HFpEF causal targets, with 58 novel targets and non-overlap between subtypes.
- Druggable candidates prioritized include IL6R, ADM, EDNRA (HFrEF) and LPA (both), with replication across ancestries.
- Pathways implicated in HFrEF include ubiquitin–proteasome, SUMOylation, inflammation, and mitochondrial metabolism.
2. Stepwise Provisional Versus Systematic Dual-Stent Strategies for Treatment of True Left Main Coronary Bifurcation Lesions.
EBC MAIN randomized 467 patients with true unprotected left-main bifurcation lesions and found no difference in 3-year MACE between stepwise provisional and upfront dual-stent strategies, while stepwise provisional significantly lowered target lesion revascularization. The trial supports using provisional stenting as the default for noncomplex left-main bifurcation PCI.
Impact: Randomized, adjudicated 3‑year outcomes in a high-stakes procedural domain change default procedural strategy and will influence operator practice and guidelines.
Clinical Implications: Adopt stepwise provisional stenting as the default for noncomplex true left-main bifurcations; reserve systematic dual stenting for bailout or clearly complex side-branch disease.
Key Findings
- No significant difference in 3-year MACE between strategies.
- Target lesion revascularization was significantly lower with stepwise provisional strategy.
- Independent adjudication and ITT analysis support robustness of findings.
3. Long-Term Lipid Lowering With Evolocumab in Older Individuals.
FOURIER plus its open-label extension show that earlier allocation to evolocumab confers similar relative cardiovascular risk reduction in patients ≥75 years as in younger patients, with larger absolute risk reduction (NNT ~19 in ≥75). Safety events were comparable across age groups over ~7 years median follow-up.
Impact: Addresses a guideline gap about intensive LDL‑lowering in older adults with hard outcome follow-up and favorable absolute benefit, influencing secondary prevention decisions in elderly ASCVD patients.
Clinical Implications: Consider evolocumab for secondary prevention in eligible older adults (≥75) as absolute benefit is substantial; incorporate geriatric considerations and cost-effectiveness into shared decision-making.
Key Findings
- Evolocumab reduced the primary composite endpoint in ≥75-year-olds (HR 0.79) with absolute risk reduction 5.4% (NNT 19).
- Relative benefit comparable to younger patients; safety event rates similar across ages over long-term follow-up.
- Open-label extension provides extended observation but carries potential bias.