Daily Cardiology Research Analysis
Analyzed 172 papers and selected 3 impactful papers.
Summary
Three standout cardiology papers advance genetics, inflammatory cardiomyopathy care, and precision risk tools. A large genome- and transcriptome-wide study delineates the polygenic architecture of bicuspid aortic valve with experimental validation. A multinational biopsy-proven registry reframes acute eosinophilic myocarditis as high-risk yet immunosuppression-responsive. An updated biomarker-based ABC-AF-bleeding 2.0 score, incorporating DOAC vs warfarin, improves bleeding risk prediction in atrial fibrillation.
Research Themes
- Polygenic architecture and mechanistic validation in congenital valve disease
- Immuno-inflammatory myocarditis outcomes and therapeutic response
- Biomarker-guided precision bleeding risk in atrial fibrillation
Selected Articles
1. Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve.
A GWAS meta-analysis and cross-tissue transcriptomics identified 36 BAV loci (32 novel) and prioritized candidate genes, with functional zebrafish knockdown/knockout validating roles in cardiac development. A polygenic risk score predicted BAV and showed pleiotropic associations in UK Biobank, indicating a substantial polygenic contribution to valve morphogenesis.
Impact: This work markedly expands the genetic landscape of BAV and bridges association signals to mechanism via in vivo validation, enabling risk prediction and target discovery.
Clinical Implications: Findings support early-life risk stratification using polygenic scores and gene-informed counseling in families, and they nominate pathways for future disease-modifying therapies.
Key Findings
- GWAS meta-analysis (9,631 cases among 65,677 participants) identified 36 loci, including 32 novel signals for BAV.
- Transcriptome-guided prioritization in human fetal/adult valves highlighted candidate genes with functional relevance.
- Knockdown/knockout of 4 candidate genes in zebrafish perturbed cardiac development, linking loci to mechanism.
- A polygenic risk score predicted BAV and showed broad phenotypic associations in UK Biobank, supporting strong polygenic architecture.
Methodological Strengths
- Large-scale GWAS meta-analysis with cross-tissue RNA-seq integration for gene prioritization
- Experimental in vivo validation (zebrafish knockdown/knockout) linking association to mechanism
Limitations
- Causal variants and cell-type–specific mechanisms remain to be resolved for many loci
- Polygenic risk score utility in diverse ancestries requires further validation
Future Directions: Fine-map causal variants, perform single-cell multi-omics in valve development, and test gene/pathway-targeted interventions in preclinical models to translate polygenic risk into prevention.
BACKGROUND: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV. METHODS: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified in zebrafish. A polygenic risk score was developed, its association with BAV was evaluated in an independent cohort, and its association with a wide range of phenotypes (n=976) was evaluated in UK Biobank (n=355 618 individuals). RESULTS: Thirty-six genomic loci were identified, including 32 that were not described previously. Among the prioritized genes, CONCLUSIONS: This study supports a significant polygenic contribution to BAV, where the combination of multiple common variants in genes involved in heart morphogenesis disrupts aortic valve development.
2. Evaluation of the updated ABC-AF-bleeding score 2.0 in patients with atrial fibrillation treated with a direct oral anticoagulant or warfarin.
In 25,962 AF patients from three pivotal DOAC–warfarin trials, the ABC-AF-bleeding 2.0 score—adding anticoagulant type to age and biomarkers (GDF-15, hemoglobin, troponin-T)—achieved superior discrimination and calibration versus HAS-BLED, ORBIT, and other clinical tools across major, GI, and intracranial bleeding.
Impact: By integrating drug class into a validated biomarker score, this study delivers a practical, superior bleeding risk tool to personalize anticoagulation in AF.
Clinical Implications: ABC-AF-bleeding 2.0 can guide anticoagulant selection and intensity, inform shared decision-making, and optimize monitoring in high-risk subgroups.
Key Findings
- Across 25,962 AF patients, ABC‑AF‑bleeding 2.0 yielded C-indices of 0.69 (major), 0.72 (GI), and 0.66 (intracranial) bleeding.
- Performance exceeded HAS‑BLED, ORBIT, and a DOAC clinical score, with better calibration.
- Superiority was consistent across clinically relevant subgroups and anticoagulant types (DOAC vs warfarin).
Methodological Strengths
- Individual participant data from three pivotal randomized DOAC–warfarin trials
- Biomarker-based model with explicit inclusion of anticoagulant class and robust discrimination metrics
Limitations
- Biomarker availability and assay standardization may limit immediate broad implementation
- Generalizability to non-trial populations and diverse ancestries needs further validation
Future Directions: Prospective implementation studies testing ABC‑AF‑bleeding 2.0–guided anticoagulation strategies on bleeding and thromboembolic outcomes; cost-effectiveness and integration into EHR decision support.
BACKGROUND: Oral anticoagulation (OAC) reduces stroke in patients with atrial fibrillation (AF), but increases bleeding. OBJECTIVES: This study aimed to evaluate an updated version of the Age, Biomarkers, and Clinical history of bleeding in AF (ABC-AF)-bleeding score (2.0) including consideration of OAC type (direct oral anticoagulant [DOAC] or warfarin) and compare its performance with other bleeding risk scores in 25 962 patients from the COMBINE AF cohort. METHODS: The COMBINE AF biomarker cohort contains individual participant data from patients with AF enrolled in 3 pivotal randomized trials comparing DOACs with warfarin. The biomarkers in the ABC-AF-bleeding score (growth differentiation factor 15, hemoglobin, and troponin-T) were analyzed in baseline samples. The biomarker-based ABC-AF-bleeding score was updated (version 2.0) by incorporating OAC type into the model (DOAC or warfarin). Discrimination was assessed by Harrell C-index and compared with clinically based bleeding scores; HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol), DOAC, and ORBIT (Older age, Reduced haemoglobin/haematocrit or history of anaemia, Bleeding history, Insufficient renal function, Treatment with antiplatelet agents). RESULTS: During follow-up, 1321 patients (5.1%) had an International Society on Thrombosis and Haemostasis major bleeding event, including 480 gastrointestinal, and 248 intracranial hemorrhages. The ABC-AF-bleeding 2.0 risk score showed better discrimination and calibration than the original version and provided superior discrimination than clinical risk scores for all outcomes. The ABC-AF-bleeding score 2.0 C-indices for major bleeding were 0.69 (95% CI, 0.68-0.71); gastrointestinal bleeding, 0.72 (95% CI, 0.69-0.74); and intracranial bleeding, 0.66 (95% CI, 0.63-0.70). The ABC-AF-bleeding score 2.0 also provided consistent superior discrimination in clinically relevant subgroups. CONCLUSION: The updated ABC-AF-bleeding score 2.0 provided better discrimination and calibration for the risk of major bleeding than clinical risk scores, which was consistent across multiple subgroups. These findings support the utility of the ABC-AF-bleeding score for advancing precision medicine in AF.
3. Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis.
In 156 biopsy-proven acute eosinophilic myocarditis cases, in-hospital death/HTx occurred in 14.7%, and 1- and 3-year death/HTx rates were 19.0% and 23.8%. Notably, only 57.4% had peripheral eosinophilia. Older age, lower admission LVEF, and absence of in-hospital immunosuppression independently predicted death/HTx, supporting biopsy for diagnosis and timely immunosuppression.
Impact: This is the largest biopsy-proven EM cohort, clarifying presentation (often without eosinophilia), prognostic factors, and association of immunosuppression with improved outcomes.
Clinical Implications: Do not rely on peripheral eosinophilia; pursue early endomyocardial biopsy when EM is suspected. Consider prompt immunosuppression and hemodynamic support, with risk stratification by age and LVEF.
Key Findings
- Only 57.4% of acute EM patients exhibited peripheral eosinophilia despite biopsy-proven disease.
- In-hospital death/HTx was 14.7%; 1- and 3-year death/HTx rates were 19.0% and 23.8%, respectively.
- Older age, lower admission LVEF, and lack of in-hospital immunosuppression independently predicted death/HTx.
- Immunosuppression during hospitalization was associated with transplant-free survival.
Methodological Strengths
- Largest multicenter, biopsy-proven EM cohort with standardized histology
- Systematic assessment of predictors and midterm outcomes
Limitations
- Retrospective design with potential treatment selection bias
- Heterogeneity in immunosuppressive regimens and supportive care across centers
Future Directions: Prospective trials to define optimal immunosuppressive regimens and timing; biomarker/imaging signatures to trigger biopsy and monitor response.
BACKGROUND: No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS: In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS: Median age at presentation was 48 years (quartile 1-3, 34-59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (quartile 1-3, 25%-48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.3% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis-associated form (13.1%) at 3 years ( CONCLUSIONS: Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION: https://www.clinicaltrials.gov; Unique identifier: NCT06447935.