Daily Cardiology Research Analysis
A long-read single-nucleus transcriptomic atlas maps full-length splicing isoforms across human heart cell types and heart failure, revealing widespread isoform heterogeneity and disease-associated shifts. A massive binational registry analysis shows smoking disproportionately accelerates atherosclerotic progression in the right coronary artery. An updated meta-analysis of randomized trials finds colchicine reduces myocardial infarction and ischemia-driven revascularization in coronary artery di
Summary
A long-read single-nucleus transcriptomic atlas maps full-length splicing isoforms across human heart cell types and heart failure, revealing widespread isoform heterogeneity and disease-associated shifts. A massive binational registry analysis shows smoking disproportionately accelerates atherosclerotic progression in the right coronary artery. An updated meta-analysis of randomized trials finds colchicine reduces myocardial infarction and ischemia-driven revascularization in coronary artery disease but increases gastrointestinal adverse events without lowering mortality.
Research Themes
- Cell-type resolved isoform biology in human heart and heart failure
- Smoking-related coronary atherosclerosis progression with right coronary artery predilection
- Anti-inflammatory therapy (colchicine) in coronary artery disease outcomes
Selected Articles
1. Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure.
Using long-read single-nucleus RNA sequencing across adult left ventricles, this study maps full-length isoforms by cell type and condition, revealing that roughly 30% of cell type-specific genes use multiple isoforms and that 379 cardiomyocyte genes switch isoform usage in heart failure. Many switches alter protein-coding sequences or involve intron retention, suggesting functional consequences. A public portal enables exploration of cell-specific isoforms to inform biomarker and target discovery.
Impact: This is the first comprehensive, cell-type resolved atlas of full-length splicing isoforms in the human heart with disease-state comparisons, providing mechanistic insights and a resource for translational research.
Clinical Implications: While not immediately practice-changing, isoform-resolved profiles can refine biomarker development, interpret genetic variation at the isoform level, and prioritize isoform-specific therapeutic targets in heart failure.
Key Findings
- Approximately 30% of cell type-specific genes in healthy left ventricles use multiple isoforms tailored to cellular programs.
- In cardiomyocytes, 379 genes exhibit marked isoform usage shifts in heart failure, many altering protein-coding sequences or switching intron retention status.
- Cell state programs often act on monoform genes, while disease-associated shifts implicate isoform-level buffering and remodeling; a public web server provides access to isoform data.
Methodological Strengths
- Long-read single-nucleus RNA sequencing capturing full-length isoforms with cell-type resolution
- Orthogonal validation (RT-qPCR and targeted amplicon sequencing) and an accessible online portal for reproducibility
Limitations
- Observational transcriptomic design limits causal inference and direct clinical translation
- Sample numbers and clinical phenotypic breadth are not fully detailed in the abstract
Future Directions: Functionally validate disease-associated isoform switches, integrate proteomics to confirm coding consequences, and leverage isoform-resolved targets in preclinical models of heart failure.
2. Efficacy and safety of colchicine in patients with coronary artery disease: An updated meta-analysis of randomized controlled trials.
Across 16 randomized trials including 20,601 patients with CAD, colchicine reduced myocardial infarction (RR 0.74) and ischemia-driven revascularization (RR 0.72) but did not lower all-cause or cardiovascular mortality. Gastrointestinal adverse events were more frequent with colchicine (RR 1.83). These data support anti-inflammatory therapy to lower recurrent ischemic events while emphasizing careful patient selection and monitoring.
Impact: Provides Level I evidence that colchicine reduces recurrent ischemic events in CAD, informing secondary prevention strategies in an accessible, low-cost therapy class.
Clinical Implications: Consider low-dose colchicine as an adjunct to guideline-directed therapy for secondary prevention in CAD patients at high ischemic risk, balancing benefits against increased gastrointestinal side effects.
Key Findings
- Colchicine reduced myocardial infarction risk (RR 0.74; 95% CI 0.59–0.93) across 16 RCTs.
- Ischemia-driven revascularization was lower with colchicine (RR 0.72; 95% CI 0.53–0.99).
- No significant reduction in all-cause or cardiovascular mortality; gastrointestinal adverse events increased (RR 1.83).
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with over 20,000 participants
- Use of random-effects modeling to account for between-trial heterogeneity
Limitations
- Heterogeneity in dosing, timing, and populations across trials may influence pooled effects
- No mortality benefit detected; safety signal for gastrointestinal adverse events warrants caution
Future Directions: Define optimal patient subgroups, dosing, and duration; evaluate long-term safety and net clinical benefit, and integrate with lipid-lowering and antithrombotic regimens.
3. Smoking and Coronary Atherosclerosis: Disproportionate Impact on the Right Coronary Artery.
In over 215,000 Swedish patients with validation in Denmark, smoking was associated with a markedly higher relative risk of plaque progression in the right coronary artery (HR 1.87) compared with the LAD, and smokers with STEMI more often had an RCA culprit lesion. The study delineates segment-specific vulnerability linked to smoking, suggesting mechanistic and preventive implications.
Impact: Massive, validated registry data reveal a novel artery-specific pattern of atherosclerosis progression in smokers, reframing risk assessment and potentially guiding targeted prevention.
Clinical Implications: Smoking cessation remains paramount; clinicians should recognize that smokers may have disproportionate RCA vulnerability, which could influence vigilance for inferior-wall ischemia and inform research on tailored preventive strategies.
Key Findings
- Smoking increased plaque progression incidence versus nonsmokers and former smokers, with the strongest relative risk in the RCA (HR 1.87) compared with LAD (HR 1.21).
- Among STEMI cases, smokers had a higher proportion of RCA culprit lesions (42.4% vs 33.1% in nonsmokers).
- Findings were validated in an independent Danish cohort, supporting robustness across populations.
Methodological Strengths
- Very large national registries with segment-level analysis and a priori validation cohort
- Long-term (up to 15 years) outcomes including progression and revascularization
Limitations
- Observational design susceptible to residual confounding and selection bias
- Angiographic assessment limited to patients undergoing clinically indicated angiography without obstructive CAD at baseline
Future Directions: Elucidate RCA-specific mechanisms (hemodynamics, wall stress, flow patterns, autonomic effects) and test whether targeted prevention reduces inferior-wall events in smokers.