Weekly Cardiology Research Analysis
This week’s cardiology literature combined mechanistic advances with pragmatic clinical trials and implementation science. Preclinical work revealed subcellular and regulated-cell-death targets (FMO2 at ER–mitochondria contacts; LRP6-mediated cuproptosis and CRAMP‑CTSL ferroptosis pathways) with translational delivery strategies. Large clinical studies and trials (multinational education RCT in AF, long-term tafamidis follow-up, ANH RCT) provided practice‑relevant evidence impacting care pathway
Summary
This week’s cardiology literature combined mechanistic advances with pragmatic clinical trials and implementation science. Preclinical work revealed subcellular and regulated-cell-death targets (FMO2 at ER–mitochondria contacts; LRP6-mediated cuproptosis and CRAMP‑CTSL ferroptosis pathways) with translational delivery strategies. Large clinical studies and trials (multinational education RCT in AF, long-term tafamidis follow-up, ANH RCT) provided practice‑relevant evidence impacting care pathways, diagnostics, and systems-level organization.
Selected Articles
1. FMO2 Prevents Pathological Cardiac Hypertrophy by Maintaining the ER-Mitochondria Association Through Interaction With IP3R2-Grp75-VDAC1.
This mechanistic study identifies FMO2 as a MAM-resident regulator that binds the IP3R2–Grp75–VDAC1 complex to preserve ER–mitochondria contacts and mitochondrial Ca2+ handling; FMO2 loss worsens and cardiac-specific overexpression prevents pathological hypertrophy in vivo.
Impact: Reveals a previously unrecognized subcellular node (MAM/FMO2) linking organelle contact integrity to maladaptive hypertrophy, opening a novel therapeutic axis distinct from canonical signaling pathways.
Clinical Implications: Although preclinical, FMO2 and MAM integrity are promising targets for therapies aiming to prevent/remodel pathological hypertrophy; development of modulators or gene therapy approaches and biomarker work are warranted.
Key Findings
- FMO2 localizes to MAMs and binds the IP3R2–Grp75–VDAC1 complex, preserving ER–mitochondria contacts and mitochondrial Ca2+ regulation.
- Cardiac FMO2 deletion aggravated hypertrophy/heart failure, whereas cardiac overexpression prevented disease progression in vivo.
2. Janus hydrogels delivering low-density lipoprotein receptor-related protein 6 inhibitor enhance myocardial repair via m6A-dependent cuproptosis in bama pigs.
This translational preclinical study uncovers LRP6-driven cuproptosis after MI via an ALKBH5–m6A–FDX1 axis and demonstrates that a Janus hydrogel patch delivering an LRP6 inhibitor (C7Og) reduces infarct size and improves function in rats and Bama miniature pigs.
Impact: Combines mechanistic discovery of a novel regulated cell‑death pathway in MI with an engineered biomaterial delivery system and efficacy in a large-animal model — a key translational milestone.
Clinical Implications: Localized LRP6 inhibition using adhesive hydrogel patches could evolve into adjunctive therapies to limit infarct expansion and adverse remodeling after MI, pending safety, PK, and human feasibility studies.
Key Findings
- MI increases myocardial copper and activates nuclear LRP6, which interacts with ALKBH5 to suppress m6A modification of FDX1 and promote cuproptosis.
- C7Og identified as an LRP6 inhibitor and delivered via a benzalkonium chloride–modified tannic acid Janus hydrogel reduced infarct size and improved function in rats and miniature pigs.
3. Education of healthcare professionals to improve guideline adherence in atrial fibrillation: the STEEER-AF cluster-randomized clinical trial.
A multinational cluster‑randomized trial across 70 centers (n=1,732) found a 16‑week structured education program for clinicians improved guideline adherence for rhythm control (adjusted RR 1.51) and patient‑reported integrated AF management, but did not significantly improve stroke‑prevention adherence.
Impact: A high‑quality, multinational implementation RCT demonstrating that clinician education can close evidence‑to‑practice gaps in AF care (for rhythm control) — directly actionable for health systems.
Clinical Implications: Health systems should deploy structured education and combine it with audit/feedback and EHR decision support to improve guideline‑adherent AF care, recognizing separate strategies may be required for stroke‑prevention adherence.
Key Findings
- Rhythm-control guideline adherence improved (adjusted RR 1.51; 95% CI 1.04–2.18; P=0.03).
- No significant improvement in stroke-prevention adherence (adjusted RR 1.10; 95% CI 0.97–1.24; P=0.13); integrated AF management improved by 5.1%.