Weekly Cardiology Research Analysis
This week’s cardiology literature highlights translational discoveries that open new molecular targets, device and procedural advances with real clinical benefit, and multiple diagnostic/imaging innovations that can be deployed rapidly. A heart-failure–specific fibroblast MYC–CXCL1–CXCR2 axis was identified as a druggable driver of contractile dysfunction, while mechanistic work on the RNA-binding enzyme NAT10 links post-transcriptional control to myocardial energetics. On the interventional fro
Summary
This week’s cardiology literature highlights translational discoveries that open new molecular targets, device and procedural advances with real clinical benefit, and multiple diagnostic/imaging innovations that can be deployed rapidly. A heart-failure–specific fibroblast MYC–CXCL1–CXCR2 axis was identified as a druggable driver of contractile dysfunction, while mechanistic work on the RNA-binding enzyme NAT10 links post-transcriptional control to myocardial energetics. On the interventional front, a drug‑eluting resorbable scaffold improved 2‑year outcomes for below‑the‑knee disease in CLTI, signaling a practical change in limb revascularization.
Selected Articles
1. Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC-CXCL1-CXCR2 axis.
Single-cell transcriptomics identified a heart‑failure–specific fibroblast state driven by MYC that secretes CXCL1, which signals via cardiomyocyte CXCR2 to impair contractility. Genetic Myc deletion in fibroblasts or blockade of the CXCL1–CXCR2 axis improved cardiac function in models, with human failing-heart fibroblasts showing the same signature.
Impact: Shifts mechanistic focus to nonmyocyte contributors to heart failure and defines a tractable chemokine axis (MYC–CXCL1–CXCR2) with genetic and pharmacologic validation, creating a new therapeutic avenue beyond cardiomyocyte‑targeted approaches.
Clinical Implications: Motivates development of CXCL1/CXCR2 or upstream MYC-modulating therapies and biomarker-driven trials to test anti‑remodeling effects in heart failure patients; suggests fibroblast-related biomarkers for patient stratification.
Key Findings
- Single-cell RNA‑seq revealed a heart-failure–specific fibroblast subcluster with high MYC expression.
- MYC directly upregulates CXCL1 in fibroblasts; CXCL1 acts on cardiomyocyte CXCR2 to depress contractility.
- Genetic deletion of Myc in fibroblasts or pharmacologic blockade of CXCL1–CXCR2 improved cardiac function in preclinical models; human failing-heart fibroblasts express the same program.
2. NAT10 regulates heart development and function by maintaining the expression of genes related to fatty acid β-oxidation and heart contraction.
Using cardiac-specific and adult-onset Nat10 knockout mice plus human iPSC‑derived cardiomyocytes, the study shows NAT10’s RNA‑binding activity is essential to maintain fatty acid β‑oxidation and contractile gene programs; loss causes dilated cardiomyopathy and heart failure, and rescue requires RNA‑binding but not acetyltransferase activity.
Impact: Reveals a previously underappreciated post‑transcriptional regulator (NAT10) linking RNA‑binding activity to myocardial energetics and contractility, opening a new axis for biomarker development and therapeutic modulation in cardiomyopathy.
Clinical Implications: Supports translational efforts to map NAT10 RNA targets in human heart failure, evaluate NAT10 pathway activity in patient tissues, and explore pharmacologic or gene‑based approaches to modulate NAT10-mediated post‑transcriptional networks.
Key Findings
- Cardiac Nat10 deletion causes dilated cardiomyopathy, heart failure, and postnatal death by downregulating fatty acid β‑oxidation and contraction genes.
- Adult-onset Nat10 knockout also yields dilated cardiomyopathy, indicating a role beyond development.
- Rescue experiments show RNA‑binding activity (not acetyltransferase activity) is required to restore gene expression and cardiac phenotypes.
3. Drug-Eluting Resorbable Scaffold Versus Balloon Angioplasty for Below-the-Knee Peripheral Artery Disease: 2-Year Results From the LIFE-BTK Trial.
In the multicenter, subject‑blinded LIFE‑BTK randomized trial (n=261), an Esprit BTK drug‑eluting resorbable scaffold improved freedom from a composite of limb amputation, vessel occlusion, clinically driven target‑lesion revascularization or restenosis at 2 years (68.8% vs 45.4% for PTA), with reduced restenosis and reintervention and similar safety.
Impact: First randomized 2‑year evidence showing a resorbable drug‑eluting scaffold outperforms PTA for infrapopliteal lesions in CLTI, offering a tangible device-based improvement in a high‑risk field with limited options.
Clinical Implications: For selected CLTI patients with suitable lesion characteristics, the Esprit BTK scaffold should be considered as an alternative to balloon angioplasty to improve patency and reduce reintervention; lesion selection and calcification assessment remain important.
Key Findings
- At 2 years, freedom from the composite failure endpoint was 68.8% with DRS vs 45.4% with PTA.
- DRS reduced restenosis and clinically driven target lesion revascularization versus PTA while maintaining comparable safety.
- Findings support patient/lesion selection criteria for DRS in infrapopliteal CLTI.