Weekly Cardiology Research Analysis
This week’s cardiology literature highlights a mix of mechanistic, therapeutic and prognostic advances: 1) a Circulation mechanistic study identifies fibroblast-specific loss of TGF-β signaling as the driver of adipogenic (fatty) scar formation after myocardial infarction — a potential disease-modifying pathway; 2) practice-informing randomized data in pediatrics show everolimus plus low-dose tacrolimus is a safe option after pediatric heart transplant with renal and CMV advantages; and 3) poole
Summary
This week’s cardiology literature highlights a mix of mechanistic, therapeutic and prognostic advances: 1) a Circulation mechanistic study identifies fibroblast-specific loss of TGF-β signaling as the driver of adipogenic (fatty) scar formation after myocardial infarction — a potential disease-modifying pathway; 2) practice-informing randomized data in pediatrics show everolimus plus low-dose tacrolimus is a safe option after pediatric heart transplant with renal and CMV advantages; and 3) pooled randomized evidence indicates SGLT2 inhibitors reduce adjudicated sudden cardiac death, supporting an expanded arrhythmic benefit. Across the week, imaging, biomarker-guided risk stratification, and longitudinal control metrics (e.g., LDL-C time-in-range) emerge as actionable themes.
Selected Articles
1. Fibroblast-Specific Loss of TGF-β Signaling Mediates Lipomatous Metaplasia in the Infarcted Heart.
Using fibroblast-restricted TGF-β receptor (TbR2) deletion in mouse MI models with lineage tracing, in vitro perturbation, and human infarct scRNA-seq, the study shows that loss of fibroblast TGF-β signaling primes fibroblasts for adipogenic conversion, replacing ~30–40% of mature scar with adipocytes and increasing early post-MI rupture risk. Human infarct fibroblasts exhibited adipocyte gene programs, supporting translational relevance.
Impact: Identifies a mechanistic, cell-specific pathway (fibroblast TGF‑β loss → fibroblast‑to‑adipocyte conversion) that explains lipomatous metaplasia after MI and points to a potentially targetable mechanism to prevent arrhythmogenic fatty scar.
Clinical Implications: Motivates development of therapies that preserve or modulate fibroblast TGF‑β signaling after MI and cautions against indiscriminate systemic TGF‑β inhibition in the post‑MI period; imaging biomarkers to detect adipogenic scar may enable targeted trials.
Key Findings
- Fibroblast-specific TbR2 deletion in MI models leads to replacement of ~30–40% of mature scar by adipocytes via fibroblast-to-adipocyte conversion.
- TbR2 loss induced a matrix-degrading fibroblast phenotype and increased early post-infarction rupture risk.
- Human infarct fibroblasts show adipocyte gene expression by scRNA-seq; in vitro TbR2 inhibition upregulated adipogenesis genes in cardiac fibroblasts.
2. Everolimus and Low-Dose Tacrolimus After Heart Transplant in Children: A Randomized Clinical Trial.
A 25-center randomized trial (n=211) randomized pediatric heart transplant survivors at 6 months to everolimus+low-dose tacrolimus versus standard-dose tacrolimus+mycophenolate for 30 months. The regimens did not differ for the primary efficacy composite (MATE‑3) at 30 months, and safety composite (MATE‑6) met noninferiority. Everolimus was associated with better eGFR at 12 months and lower CMV infection rates.
Impact: A rare, adequately powered multicenter pediatric RCT addressing long-standing uncertainty about mTOR-based regimens after pediatric heart transplant, demonstrating safety and renal/virologic advantages that may change practice.
Clinical Implications: For clinically stable pediatric heart transplant recipients at 6 months, transitioning to everolimus with low-dose tacrolimus is a reasonable option to consider for renal preservation and reduced CMV risk while maintaining rejection control; long-term surveillance for CAV and malignancy remains warranted.
Key Findings
- No difference in MATE‑3 composite at 30 months between regimens (mean difference −0.32; P=0.16).
- Safety noninferiority met for MATE‑6; overall burden not higher in the everolimus arm.
- Improved eGFR at 12 months with everolimus (+10.5 mL/min/1.73 m2) and lower CMV infection (HR 0.50).
3. Impact of empagliflozin and dapagliflozin on sudden cardiac death: A systematic review and meta-analysis of adjudicated randomized evidence.
A meta-analysis of 8 randomized trials (n=58,569; median follow-up 29 months) found SGLT2 inhibitors (empagliflozin and dapagliflozin) reduced adjudicated sudden cardiac death (OR 0.82; 95% CI 0.72–0.94). Heterogeneity was minimal and effects were consistent across diabetes, heart failure, and CKD populations, suggesting a class anti‑arrhythmic benefit beyond established cardio‑renal endpoints.
Impact: Addresses an important unresolved clinical question with adjudicated RCT evidence, supporting the view that SGLT2 inhibitors confer an arrhythmic mortality benefit in addition to heart failure and renal outcomes.
Clinical Implications: Clinicians prescribing SGLT2 inhibitors for patients with T2D, heart failure, or CKD should consider potential reduction in sudden cardiac death as an additional benefit; however, this does not replace device-based ICD indications and further trials with arrhythmic endpoints and rhythm monitoring are warranted.
Key Findings
- Across 8 RCTs (n=58,569), SGLT2 inhibitors reduced adjudicated sudden cardiac death (OR 0.82; 95% CI 0.72–0.94).
- Median follow-up ~29 months; minimal heterogeneity supports robustness.
- Effects were consistent across T2D, heart failure, and CKD trial populations, suggesting a class effect.