Daily Cardiology Research Analysis
Three impactful cardiology studies stood out today: (1) a mechanistic European Heart Journal paper links periodontitis to post-MI myocardial fibrosis via collagen-producing SiglecF+ neutrophils; (2) a large prospective JAMA Cardiology registry shows invasive coronary function testing is safe and highly diagnostic across tertiary and non-tertiary centers for ANOCA; and (3) a JACC: CardioOncology large-animal randomized study demonstrates dose-dependent cardioprotection by empagliflozin against an
Summary
Three impactful cardiology studies stood out today: (1) a mechanistic European Heart Journal paper links periodontitis to post-MI myocardial fibrosis via collagen-producing SiglecF+ neutrophils; (2) a large prospective JAMA Cardiology registry shows invasive coronary function testing is safe and highly diagnostic across tertiary and non-tertiary centers for ANOCA; and (3) a JACC: CardioOncology large-animal randomized study demonstrates dose-dependent cardioprotection by empagliflozin against anthracycline-induced cardiotoxicity by preserving myocardial energetics.
Research Themes
- Oral-systemic immunity and myocardial fibrosis
- Coronary vasomotor dysfunction diagnostics in ANOCA
- Cardio-oncology prevention with SGLT2 inhibitors
Selected Articles
1. Periodontitis-related myocardial fibrosis by expansion of collagen-producing SiglecF+ neutrophils.
In multi-cohort human data and complementary mouse models, persistent periodontitis worsened post-MI remodeling via expansion of a GM-CSF/TGFβ–PPARγ–driven SiglecF+ neutrophil subset that deposits collagen and activates fibroblasts. Depletion of SiglecF+ neutrophils mitigated myocardial fibrosis, linking oral health to cardiac repair outcomes.
Impact: This study identifies a previously unrecognized collagen-producing neutrophil program as a driver of cardiac fibrosis after MI and establishes a mechanistic link between periodontitis and adverse cardiac remodeling.
Clinical Implications: Screening and management of periodontitis should be integrated into MI care pathways. Targeting SiglecF+ neutrophil pathways (e.g., GM-CSF/TGFβ–PPARγ signaling, local depletion strategies) may offer novel antifibrotic therapies.
Key Findings
- Persistent, not short-term, periodontitis worsened post-MI fibrosis and function in humans and mice.
- Bone marrow neutrophils in PD were skewed towards longer-lived SiglecF+ neutrophils via GM-CSF/TGFβ in a PPARγ-dependent manner.
- SiglecF+ neutrophils deposited collagen and activated fibroblasts in infarcted hearts; depleting them reduced fibrosis.
Methodological Strengths
- Triangulation across three prospective human cohorts and mechanistic mouse models
- State-of-the-art single-cell RNA sequencing and functional perturbations (adoptive transfer, conditional knockout, targeted depletion)
Limitations
- Causality in humans is inferred; interventional human trials are lacking
- Potential sex/species differences (male mouse data emphasized) and unmeasured confounding in cohorts
Future Directions: Test oral-health interventions and neutrophil-targeted strategies to reduce post-MI fibrosis; validate SiglecF+ neutrophil biomarkers for risk stratification.
2. SGLT2i Therapy Prevents Anthracycline-Induced Cardiotoxicity in a Large Animal Model by Preserving Myocardial Energetics.
In a randomized large-animal model, empagliflozin preserved LVEF (57.5% vs 47.0% control) and eliminated AIC events at 20 mg while enhancing ketone utilization and preserving myocardial energetics and mitochondrial integrity. Effects were dose-dependent and consistent across imaging, metabolomics, and ultrastructure.
Impact: Provides robust translational evidence that SGLT2 inhibition can prevent chemotherapy cardiotoxicity by metabolic reprogramming, supporting imminent clinical trials in cardio-oncology.
Clinical Implications: Empagliflozin prophylaxis may protect high-risk patients receiving anthracyclines; dose selection (e.g., 20 mg) and timing merit clinical testing with safety monitoring.
Key Findings
- Empagliflozin 20 mg preserved LVEF (median 57.5%) versus doxorubicin control (47.0%), P=0.027.
- AIC events occurred in 0% (20 mg), 50% (10 mg), and 72% (control), indicating dose-dependent protection.
- Mechanistic readouts showed increased myocardial ketone uptake, preserved energetics by MRS, and improved mitochondrial structure and respiration.
Methodological Strengths
- Randomized large-animal study with multiparametric CMR/MRS and mechanistic assays (metabolomics, EM, respirometry)
- Dose–response evaluation and prespecified primary endpoint (LVEF)
Limitations
- Preclinical (porcine) data; external validity to humans uncertain
- Single anthracycline regimen and female animals may limit generalizability
Future Directions: Randomized clinical trials to test SGLT2i prophylaxis in patients receiving anthracyclines, with biomarker and imaging substudies to validate energetic mechanisms.
3. Safety, Feasibility, and Diagnostic Yield of Invasive Coronary Function Testing: Netherlands Registry of Invasive Coronary Vasomotor Function Testing.
In a 15-center prospective registry of 1207 ANOCA patients (81% women), invasive coronary function testing identified vasomotor dysfunction in 78% with low complication rates (0.9% major; no death/MI/stroke) and comparable safety in tertiary and non-tertiary centers.
Impact: Establishes real-world safety and high diagnostic yield of invasive coronary function testing across hospital tiers, supporting broader implementation for ANOCA.
Clinical Implications: CFT can be safely performed beyond expert centers to phenotype ANOCA (spasm/microvascular dysfunction) and guide targeted therapy, particularly in women.
Key Findings
- Vasomotor dysfunction prevalence was 78% among 1207 ANOCA patients undergoing complete CFT.
- Complication rates were low (0.9% major, 0.8% minor) with no procedural death, MI, or stroke.
- Safety was similar between tertiary and non-tertiary centers, supporting broader feasibility.
Methodological Strengths
- Prospective, multicenter national registry including non-tertiary centers
- Standardized CFT protocol (acetylcholine provocation and microcirculatory assessment) with explicit safety tracking
Limitations
- Observational design with potential referral bias; no randomized comparison
- No long-term outcomes reported to link endotypes to prognosis or treatment response
Future Directions: Integrate CFT-guided therapy trials and develop scalable training pathways for non-tertiary centers; evaluate long-term outcomes and cost-effectiveness.