Weekly Cardiology Research Analysis
This week’s cardiology literature emphasizes physiology‑guided care, powerful new metabolic pharmacotherapies, and mechanistic target discovery. A randomized PET‑guided comprehensive care trial reduced death and MI in chronic CAD, a phase‑3 trial of the GLP‑1/glucagon dual agonist mazdutide produced large clinically meaningful weight loss with broad cardiometabolic benefits, and preclinical multi‑omics work identified GSTM1/ferroptosis modulation as a candidate to limit post‑MI fibrosis. Across
Summary
This week’s cardiology literature emphasizes physiology‑guided care, powerful new metabolic pharmacotherapies, and mechanistic target discovery. A randomized PET‑guided comprehensive care trial reduced death and MI in chronic CAD, a phase‑3 trial of the GLP‑1/glucagon dual agonist mazdutide produced large clinically meaningful weight loss with broad cardiometabolic benefits, and preclinical multi‑omics work identified GSTM1/ferroptosis modulation as a candidate to limit post‑MI fibrosis. Across studies, imaging, hemodynamic trajectories, and genomics are increasingly used to personalize risk and guide interventions.
Selected Articles
1. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.
Phase‑3 double‑blind randomized trial in 610 adults showed once‑weekly mazdutide 4 mg and 6 mg produced mean weight reductions of −11.0% and −14.0% at 48 weeks, with 35.7–49.5% achieving ≥15% loss. Broad cardiometabolic improvements were seen and adverse events were predominantly mild‑to‑moderate gastrointestinal symptoms with low discontinuation rates.
Impact: Demonstrates robust and clinically meaningful weight loss with a novel GLP‑1/glucagon dual agonist, with concurrent cardiometabolic benefits that could translate into long‑term cardiovascular risk reduction if sustained.
Clinical Implications: Mazdutide expands therapeutic options for obesity management in cardiometabolic care and may enable larger weight losses than prior agents; clinicians should monitor GI tolerability and await longer‑term CV outcome data to guide integration into practice.
Key Findings
- At 48 weeks mean weight change was −11.00% (4 mg) and −14.01% (6 mg) vs +0.30% placebo.
- Large proportions achieved clinically meaningful thresholds (≥5% and ≥15% loss); cardiometabolic measures improved broadly.
- Adverse events were mainly GI, mostly mild-to-moderate, with low discontinuation.
2. Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease: the CENTURY trial.
A randomized trial (n=1,028) comparing a comprehensive program (intensive lifestyle, goal‑directed medical therapy, PET‑derived coronary flow capacity [CFC] to triage revascularization) vs usual care showed reduced 11‑year all‑cause death (4.7% vs 8.2), death or MI, late revascularization, and MACE. Early revascularization was uncommon and reserved for severely reduced CFC.
Impact: Provides randomized, long‑term evidence that physiology‑guided, integrated lifestyle and medical care with selective revascularization improves hard outcomes in chronic CAD — a potential paradigm shift away from anatomy‑first strategies.
Clinical Implications: Consider implementing PET‑CFC assessment in care pathways to prioritize aggressive medical/lifestyle management and reserve revascularization for those with severely reduced physiological capacity; health systems should evaluate resource and access implications.
Key Findings
- Comprehensive PET‑CFC–guided care reduced 11‑year all‑cause mortality (4.7% vs 8.2%) and death/MI (7.0% vs 11.1%).
- Late revascularization and overall MACE were significantly lower in the comprehensive arm; early revascularization was uncommon (5.4%).
- Intervention combined intensified lifestyle, goal‑directed therapy, frequent follow‑up and selective revascularization based on CFC.
3. GSTM1 suppresses cardiac fibrosis post-myocardial infarction through inhibiting lipid peroxidation and ferroptosis.
Preclinical multi‑omics and mechanistic study using proteomics, scRNA‑seq, AAV9 cardiac GSTM1 overexpression, lipidomics, and fibroblast assays showed GSTM1 is downregulated post‑MI and that restoring GSTM1 reduces lipid peroxidation, ferroptosis markers, infarct size, fibrosis, and improves function via STAT3→GPX4 signaling.
Impact: Identifies a tractable ferroptosis‑centered pathway (GSTM1–STAT3–GPX4) with gene‑delivery proof‑of‑concept to limit post‑MI fibrosis, opening translational opportunities to alter remodeling and heart failure progression.
Clinical Implications: Although preclinical, GSTM1 modulation suggests new therapeutic strategies to prevent maladaptive remodeling after MI; priority next steps include large‑animal validation and safety/dosing evaluation for gene or small‑molecule approaches.
Key Findings
- GSTM1 is downregulated in post‑MI cardiac fibroblasts and in fibrotic human DCM samples.
- AAV9‑mediated cardiac GSTM1 overexpression reduced infarct size, fibrosis, lipid peroxidation, free Fe2+, and ferroptosis markers, and improved function.
- Mechanism involves enhanced STAT3 phosphorylation and upregulation of GPX4, with reduced oxidized lipid species.