Daily Cardiology Research Analysis
Three studies stand out today: a JCI mechanistic paper identifies a smooth muscle lncRNA (CARMN) as a regulator of angiogenesis via the miR-143-3p–HHIP–Hedgehog axis in chronic limb-threatening ischemia; a national TVT Registry analysis suggests balloon-expandable valve-in-valve TAVR has favorable 5-year outcomes compared with native TAVR; and a multicenter cohort shows that preoperative NT-proBNP reduction predicts better 30-day and 5-year outcomes after cardiac surgery.
Summary
Three studies stand out today: a JCI mechanistic paper identifies a smooth muscle lncRNA (CARMN) as a regulator of angiogenesis via the miR-143-3p–HHIP–Hedgehog axis in chronic limb-threatening ischemia; a national TVT Registry analysis suggests balloon-expandable valve-in-valve TAVR has favorable 5-year outcomes compared with native TAVR; and a multicenter cohort shows that preoperative NT-proBNP reduction predicts better 30-day and 5-year outcomes after cardiac surgery.
Research Themes
- Translational mechanisms and targets in peripheral artery disease
- Real-world outcomes of structural heart interventions
- Biomarker-guided perioperative risk optimization
Selected Articles
1. A smooth muscle cell lncRNA controls angiogenesis in chronic limb-threatening ischemia through miR-143-3p/HHIP signaling.
This mechanistic study identifies CARMN as a smooth muscle-enriched lncRNA that promotes angiogenesis via a miR-143-3p–HHIP–Hedgehog axis in limb ischemia. Loss of CARMN impairs capillary formation and perfusion, whereas miR-143-3p mimics or HHIP silencing rescue endothelial defects and restore blood flow.
Impact: It reveals a tractable SMC–EC signaling axis for therapeutic angiogenesis in CLTI, highlighting miR-143-3p/HHIP as targets with in vivo rescue evidence.
Clinical Implications: Therapies enhancing miR-143-3p or inhibiting HHIP could augment angiogenesis and perfusion in CLTI. It supports cell–cell crosstalk–based strategies beyond VEGF-centric approaches.
Key Findings
- CARMN is downregulated in human CLTI muscle and is SMC-enriched.
- CARMN knockout impairs capillary density and blood flow recovery after limb ischemia.
- CARMN regulates Hedgehog signaling via miR-143-3p targeting HHIP; miR-143-3p or HHIP siRNA rescues endothelial angiogenic defects and perfusion.
Methodological Strengths
- Multimodal validation including knockout mice, endothelial functional assays, and RNA-seq pathway analysis
- In vivo rescue experiments (miR-143-3p mimic, HHIP siRNA) demonstrating causality
Limitations
- Preclinical models; human interventional data are lacking
- Delivery, specificity, and durability of miRNA/siRNA therapies remain to be established
Future Directions: Develop targeted delivery systems for miR-143-3p/HHIP modulation, validate efficacy and safety in large-animal models, and progress to early-phase trials in CLTI.
2. Mid-Term Outcomes of Balloon-Expandable Aortic Valve-in-Valve Replacement in the United States.
In a propensity-matched TVT Registry analysis (13,638 pairs), balloon-expandable valve-in-valve TAVR showed lower 5-year death and stroke compared with native TAVR. Hemodynamics were favorable, particularly with SAPIEN 3 Ultra RESILIA, supporting the safety and durability of AViV across risk strata.
Impact: Largest real-world, mid-term comparison indicates AViV may confer survival and cerebrovascular advantages over native TAVR, informing structural heart strategies in failed surgical bioprostheses.
Clinical Implications: For degenerated surgical valves, AViV with BEVs appears safe and durable at 5 years and may be favored over native TAVR in appropriate anatomy; device selection (e.g., RESILIA) affects gradients.
Key Findings
- Propensity-matched analysis (13,638 pairs) showed lower 5-year death (43.1% vs 55.2%) and stroke (10.5% vs 11.8%) with AViV vs native TAVR.
- SAPIEN 3 Ultra RESILIA had lower discharge gradients across all valve sizes compared with predecessors.
- Outcomes were consistent across STS risk tertiles; no 5-year death/stroke difference between stented and stentless prior surgical valves.
Methodological Strengths
- Very large national registry with propensity matching and 5-year follow-up
- Subgroup analyses by risk, device subtype, and surgical valve type
Limitations
- Observational design with residual confounding despite matching
- Heterogeneity in centers, devices, and evolving practice over inclusion period
Future Directions: Prospective comparative studies of AViV strategies, optimization of device sizing/BEV choice, and durability assessments beyond 5 years.
3. Prognostic Implications of Preoperative N-Terminal Pro-B-Type Natriuretic Peptide Dynamics in Patients Undergoing Cardiac Surgery.
In 6,938 consecutive cardiac surgery patients with external validation, lower preoperative NT-proBNP and reductions from diagnostic levels were independently associated with lower 30-day and 5-year mortality and less resource use. Optimizing patients to reduce NT-proBNP before surgery may improve outcomes.
Impact: Links a modifiable biomarker trajectory to perioperative and long-term outcomes, providing an actionable target for prehabilitation and risk optimization.
Clinical Implications: Incorporate NT-proBNP dynamics into preoperative assessment; consider optimization strategies (e.g., decongestion, GDMT titration) to lower NT-proBNP prior to surgery to reduce mortality and resource use.
Key Findings
- High preoperative NT-proBNP predicted higher 30-day and 5-year mortality after cardiac surgery.
- Patients whose high NT-proBNP decreased below 3,000 ng/L before surgery had lower 30-day mortality (HR 0.21) and improved 5-year survival.
- NT-proBNP reduction associated with shorter ICU stay and less ultrafiltration and ECMO use; findings validated in SWEDEHEART.
Methodological Strengths
- Large consecutive cohort with EuroSCORE II–adjusted models and external validation
- Trajectory analysis of biomarker dynamics rather than single-point measurement
Limitations
- Observational design cannot prove causality; unmeasured confounding possible
- Specific optimization interventions to lower NT-proBNP were not tested
Future Directions: Randomized trials testing preoperative optimization strategies targeting NT-proBNP reduction and integration into perioperative risk algorithms.