Daily Cardiology Research Analysis
Analyzed 274 papers and selected 3 impactful papers.
Summary
Analyzed 274 papers and selected 3 impactful articles.
Selected Articles
1. Extended Dual Antiplatelet Therapy for Multivessel Coronary Artery Disease.
In a multicenter randomized trial of 8,250 event-free patients with multivessel CAD one year after DES implantation, continuing clopidogrel plus aspirin for an additional 12 months reduced the composite of cardiovascular death, nonfatal MI, or nonfatal stroke versus switching to aspirin alone, without increasing clinically relevant or major bleeding. Median follow-up was 34.3 months.
Impact: This large RCT directly informs antiplatelet duration in multivessel CAD, demonstrating fewer ischemic events without excess bleeding when extending DAPT beyond one year.
Clinical Implications: For event-free multivessel CAD patients 12 months post-DES and without high bleeding risk, extending clopidogrel plus aspirin for another 12 months is a reasonable strategy to reduce ischemic events. Individualize by ischemic vs bleeding risk and consider clopidogrel-based regimens in similar populations.
Key Findings
- Primary composite endpoint at 36 months: 5.8% with extended DAPT vs 6.8% with aspirin alone (HR 0.82; 95% CI 0.69–0.98; P=0.03).
- Clinically relevant or major bleeding: 1.4% vs 1.5% (HR 0.89; 95% CI 0.61–1.30; P=0.54).
- Population: 8,250 patients aged 18–75 with multivessel CAD, event-free for 12 months after DES; median follow-up 34.3 months.
Methodological Strengths
- Large, multicenter randomized design with prespecified efficacy and safety endpoints.
- Adequate follow-up (median 34.3 months) and trial registration (NCT04624854).
Limitations
- Open-label design may introduce performance/ascertainment bias.
- Conducted in China with clopidogrel-based DAPT; generalizability to other regions and P2Y12 agents may be limited.
Future Directions: Head-to-head comparisons with ticagrelor/prasugrel-based strategies, evaluation in broader geographies, and precision risk models to tailor DAPT duration in multivessel CAD.
BACKGROUND: Patients with multivessel coronary artery disease often receive 12 months of dual antiplatelet therapy (DAPT) after stenting to reduce the risk of ischemic events. Whether extending DAPT beyond 12 months in event-free patients with multivessel disease provides a benefit is uncertain. METHODS: We conducted an open-label, randomized trial at 97 centers in China. Patients 18 to 75 years of age with multivessel coronary artery disease who had no major ischemic or bleeding events while receiving DAPT for 12 months after implantation of a drug-eluting stent were randomly assigned in a 1:1 ratio to receive an additional 12 months of DAPT (clopidogrel plus aspirin) or aspirin monotherapy. The primary efficacy end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary safety end point was clinically relevant or major bleeding (i.e., a bleeding event of Bleeding Academic Research Consortium [BARC] type ≥2; BARC types range from 0 to 5, with higher values indicating greater severity of bleeding). RESULTS: A total of 8250 patients were randomly assigned to receive extended DAPT (4125 patients) or aspirin monotherapy (4125 patients). The median follow-up was 34.3 months. A primary efficacy end-point event occurred in 222 patients in the DAPT group and in 266 patients in the aspirin-monotherapy group (36-month Kaplan-Meier cumulative incidence, 5.8% vs. 6.8%; hazard ratio, 0.82; 95% confidence interval [CI], 0.69 to 0.98; P = 0.03). Clinically relevant or major bleeding occurred in 51 patients in the DAPT group and in 57 patients in the aspirin-monotherapy group (36-month Kaplan-Meier cumulative incidence, 1.4% vs. 1.5%; hazard ratio, 0.89; 95% CI, 0.61 to 1.30; P = 0.54). CONCLUSIONS: Among patients with multivessel coronary artery disease who were in stable condition 12 months after implantation of a drug-eluting stent, extending DAPT with clopidogrel and aspirin for an additional 12 months led to a lower risk of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke than continuing aspirin alone, without an increased risk of bleeding. (Funded by the National Natural Science Foundation of China and others; DAPT-MVD ClinicalTrials.gov number, NCT04624854.).
2. Single-cell transcriptomics uncovers endothelial progenitor-like remodelling driving human coronary atherosclerosis progression.
Using single-cell RNA sequencing of 27,941 cells from 56 human coronary segments, the authors built a disease-stage-resolved atlas of coronary atherosclerosis and identified a pathological endothelial progenitor-like state (EC5). Findings implicate endothelial plasticity as a driver of lesion progression and suggest stage-specific therapeutic targets and biomarkers.
Impact: This work provides a high-resolution, human-derived cellular roadmap of coronary atherosclerosis and uncovers an endothelial progenitor-like program that reframes therapeutic thinking around endothelial plasticity.
Clinical Implications: Highlights endothelial plasticity as a potential drug target and source of biomarkers; enables stage-aware strategies to modulate endothelial states and refine risk stratification.
Key Findings
- Constructed a disease-stage-resolved single-cell atlas from 27,941 cells across 56 human coronary segments.
- Identified a pathological endothelial progenitor-like state (EC5) emerging with atherosclerosis progression.
- Revealed dynamic shifts in endothelial cell composition and phenotypes across disease stages.
Methodological Strengths
- Human tissue single-cell RNA sequencing across multiple disease stages.
- Comprehensive, stage-resolved cellular atlas enabling hypothesis generation for targeted interventions.
Limitations
- Primarily observational transcriptional data without direct causal or functional validation in vivo.
- Potential dissociation and sampling biases; longitudinal progression not directly observed.
Future Directions: Combine spatial multi-omics and perturbation studies to validate causal roles of EC5 and test modulators of endothelial state transitions in preclinical models.
Coronary atherosclerosis underlies life-threatening conditions such as myocardial infarction and stroke, yet its cellular dynamics remain incompletely understood. Here, through single-cell RNA sequencing of 27,941 cells from 56 human coronary segments, we constructed a disease-stage-resolved cellular atlas, revealing pathological remodelling of endothelial cells (ECs) into a progenitor-like state (EC5
3. Trientine for hypertrophic cardiomyopathy: a phase 2 trial.
In a multicenter, placebo-controlled phase 2 RCT (n=154) of hypertrophic cardiomyopathy, trientine 400 mg BID for 52 weeks reduced LV mass index more than placebo (between-group difference −3.2 g/m2; P=0.009). Effects were greater in patients with higher baseline LV mass and were mediated by reductions in myocardial cellular mass; adverse events were similar between groups.
Impact: This is among the first randomized clinical evidence that targeting copper biology can modify myocardial structure in HCM, suggesting a novel disease-modifying therapeutic avenue beyond symptom control.
Clinical Implications: Trientine may represent a disease-modifying option to reduce LV mass in HCM, particularly in patients with higher baseline LV mass. Confirmation in phase 3 trials with clinical endpoints (symptoms, hospitalization, arrhythmias) is needed before routine adoption.
Key Findings
- LV mass index decreased more with trientine vs placebo over 52 weeks (between-group difference −3.2 g/m2; 95% CI −5.6 to −0.8; P=0.009).
- Greater efficacy at higher baseline LV mass (treatment-by-baseline interaction P=0.015).
- Mediation analysis indicated reduction in myocardial cellular mass (ACME −3.9 g/m2; 95% CI −6.8 to −0.9).
- Adverse event rates were similar between groups.
Methodological Strengths
- Placebo-controlled randomized design with prespecified primary CMR endpoint.
- Mechanistic mediation analysis linking structural change to cellular mass reduction.
Limitations
- Phase 2 size with surrogate primary endpoint; limited power for clinical outcomes.
- Population largely NYHA I and mixed obstructive status; generalizability to higher-risk HCM uncertain.
Future Directions: Conduct phase 3 trials powered for clinical endpoints, assess arrhythmic burden, exercise capacity, and reverse remodeling durability; explore biomarkers for response enrichment.
BACKGROUND AND AIMS: Pathophysiological features of hypertrophic cardiomyopathy include left ventricular hypertrophy, myocardial fibrosis, and myocardial energy deficiency. Depletion of cardiomyocyte copper I ions leads to impaired mitochondrial function, a state associated with left ventricular hypertrophy. Unbound or loosely bound copper II ions activate profibrotic pathways. Trientine dihydrochloride improves intracellular copper I ion trafficking and availability, and chelates copper II ions. In preclinical studies, trientine improved myocardial mitochondrial function and reduced left ventricular hypertrophy and fibrosis. The efficacy and safety of trientine in persons with hypertrophic cardiomyopathy are unknown. METHODS: In this multicentre, placebo-controlled phase 2 trial, adults with hypertrophic cardiomyopathy, a left ventricular wall thickness of 15 mm or greater, and who were in New York Heart Association class I to III were randomly assigned to receive trientine 400 mg twice daily or placebo for 52 weeks. Patients with any left ventricular outflow tract (LVOT) gradient were eligible. The primary endpoint was the change in left ventricular mass indexed to body surface area measured using cardiovascular magnetic resonance. RESULTS: A total of 154 patients underwent randomization. The mean age was 53.4 years, median maximum left ventricular wall thickness was 20.0 mm, median maximum LVOT gradient was 6.0 mmHg, 18.6% of patients had a resting LVOT gradient ≥30 mmHg, and 61.7% were in New York Heart Association class I. At 52 weeks, the mean change in the left ventricular mass indexed to body surface area was -4.4 ± 7.7 g/m2 in the trientine group and -1.5 ± 6.1 g/m2 in the placebo group (between-group difference -3.2 g/m2; 95% confidence interval -5.6 to -0.8; P = .009). The efficacy of trientine increased at higher levels of baseline left ventricular mass (baseline left ventricular mass indexed to body surface area by treatment allocation interaction P = .015). The effect of trientine was mediated via a reduction in myocardial cellular mass (average causal mediated effect -3.9 g/m2; 95% confidence interval -6.8 to -0.9). The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among patients with hypertrophic cardiomyopathy, treatment with trientine resulted in a significantly greater reduction in left ventricular mass indexed to body surface area than placebo. (Funded by NIHR; TEMPEST ClinicalTrials.gov number, NCT04706429).