Weekly Cardiology Research Analysis
This week’s cardiology literature highlights three high-impact advances: a validated serum biomarker (NOTCH3‑ECD) for idiopathic pulmonary arterial hypertension, discovery of an extracellular microprotein (BRICK1) that drives post‑infarction angiogenesis, and a head‑to‑head randomized trial showing the myosin inhibitor aficamten improves patient‑reported health status vs metoprolol in obstructive HCM. Across the week, studies also advanced AI-enabled risk prediction, imaging prognostication afte
Summary
This week’s cardiology literature highlights three high-impact advances: a validated serum biomarker (NOTCH3‑ECD) for idiopathic pulmonary arterial hypertension, discovery of an extracellular microprotein (BRICK1) that drives post‑infarction angiogenesis, and a head‑to‑head randomized trial showing the myosin inhibitor aficamten improves patient‑reported health status vs metoprolol in obstructive HCM. Across the week, studies also advanced AI-enabled risk prediction, imaging prognostication after STEMI, and multi‑omic insights linking coagulation, inflammation, and vascular risk. Several findings have near‑term translational potential for diagnostics, patient selection, and targeted therapeutics.
Selected Articles
1. The NOTCH3 extracellular domain is a serum biomarker for pulmonary arterial hypertension.
Across three independent cohorts (341 IPAH cases, 376 controls), serum NOTCH3‑ECD concentrations were significantly elevated in idiopathic pulmonary arterial hypertension, mechanistically consistent with constitutive NOTCH3 cleavage in diseased lungs. The biomarker showed reproducible differences versus controls and may assist noninvasive diagnosis and monitoring after prospective thresholding and validation.
Impact: Identifies and validates a mechanistically grounded circulating biomarker for a lethal and diagnostically challenging disease, addressing an unmet clinical need and enabling easier screening and disease tracking.
Clinical Implications: Pending assay standardization and prospective studies, NOTCH3‑ECD could be incorporated into PAH diagnostic algorithms to triage patients for right heart catheterization and to monitor treatment response.
Key Findings
- Serum NOTCH3‑ECD is significantly elevated in IPAH patients vs healthy controls across three geographically distinct cohorts.
- The biomarker aligns with known pulmonary NOTCH3 cleavage, supporting biological plausibility and translational potential.
2. Extracellular BRICK1 drives heart repair after myocardial infarction in mice.
This mechanistic study identifies BRICK1, a 75‑amino‑acid microprotein released from dying myeloid cells, as an indispensable extracellular driver of post‑infarction angiogenesis in mice with supporting human tissue observations. The finding reveals an unexpected extracellular role for a WAVE complex subunit and defines a novel myeloid–endothelial repair axis.
Impact: Provides a novel mechanistic target (extracellular BRICK1) for enhancing post‑MI repair and angiogenesis, opening new therapeutic and biomarker avenues in cardiac regeneration research.
Clinical Implications: Preclinical now, but BRICK1 or its downstream pathways could become targets or biomarkers to promote angiogenesis and limit infarct scarring if safety, dosing, and delivery are demonstrated in larger animal models and early human studies.
Key Findings
- BRICK1 is preferentially expressed in myeloid cells and relocates extracellularly after MI in mice and humans.
- BRICK1 released during myeloid cell death is required for post‑infarction angiogenesis in reperfused MI models.
3. Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy.
In a double‑blind, randomized head‑to‑head trial of 175 symptomatic obstructive HCM patients, aficamten produced a greater 24‑week improvement in KCCQ Overall Summary Score than metoprolol (+7.8 points adjusted), with more patients experiencing very large clinically meaningful improvements and fewer deteriorations.
Impact: A rigorous head‑to‑head RCT demonstrating superior patient‑centered symptomatic benefit of a disease‑specific myosin inhibitor over standard beta‑blockade directly informs frontline therapeutic decision‑making.
Clinical Implications: Clinicians managing symptomatic obstructive HCM should consider aficamten as an initial monotherapy option to prioritize symptom and quality‑of‑life gains, while monitoring long‑term safety and event outcomes as further data accrue.
Key Findings
- Adjusted between‑group difference in KCCQ‑OSS at 24 weeks: +7.8 points favoring aficamten (P < 0.001).
- Higher proportion of very large (≥20 points) KCCQ improvements with aficamten (38.6% vs 18.4%), and fewer patients worsened.