Daily Cardiology Research Analysis

BACKGROUNDS AND AIMS: Patients with periodontitis (PD) are prone to developing myocardial infarction (MI), yet the prognosis and mechanisms remain unclear. Given the presumed close association of neutrophils with both conditions, this study aims to elucidate the roles of neutrophils in mediating the interaction between PD and MI. METHODS: Three prospective cohorts and PD + MI mouse model were investigated to assess the effects of PD on MI prognosis. Single-cell-RNA sequencing and genome-wide association study were employed to identify the neutrophil subtype involved. To characterize the function of SiglecF+ neutrophils, bone marrow transplantation, Edu-pulse chasing, lineage tracing, and collagen contraction assay were utilized. Adoptive neutrophil transfer, conditional Siglecf knockout and lipid nanoparticles facilitating local SiglecF+ neutrophils depletion was harnessed to explore the roles of SiglecF+ neutrophils in MI repair. RESULTS: Persisting but not short-term PD upset MI prognosis (cardiac fibrosis and function) in human and mice. Bone marrow neutrophils of PD were intrinsically skewed toward longer-lived SiglecF+ neutrophil differentiation, a subtype that was converted by GMCSF or TGFβ in PPARγ-dependent manner. SiglecF+ neutrophils were expanded in infarcted PD heart where they deposit collagen and activate fibroblasts to instigate excessive fibrosis. SiglecF+ neutrophil depletion was efficacious for mitigating fibrosis. CONCLUSIONS: This study demonstrated that long-lasting PD-aggravated MI prognosis by expanding scar-associated SiglecF+ neutrophils into the heart and highlighted the clinical relevance of oral health examination for treating MI in a holistic fashion.

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC) is characterized by a disruption in myocardial metabolism. OBJECTIVES: The authors used a large animal model to test sodium-glucose cotransporter inhibitor therapy to prevent AIC. METHODS: Female large white pigs (n = 36) were used to identify the most translational AIC regimen: 6 triweekly intravenous doxorubicin injections (1.8 mg/kg each). Another group of 32 pigs were randomized (1:1:2) to doxorubicin plus empagliflozin 20 mg, doxorubicin plus empagliflozin 10 mg, or doxorubicin control. Pigs were serially examined using multiparametric cardiac magnetic resonance and magnetic resonance spectroscopy. At the end of the 21-week follow-up period, blood samples were obtained to measure myocardial metabolic substrate extraction, and the left ventricle was harvested and processed for analysis using metabolomics, transmission electron microscopy, mitochondrial respirometry, and histopathology. RESULTS: Final left ventricular ejection fraction (LVEF), the prespecified primary outcome, was significantly higher in pigs receiving 20 mg empagliflozin than in the doxorubicin control group (median 57.5% [Q1-Q3: 55.5%-60.3%] vs 47.0% [Q1-Q3: 40.8%-47.8%]; P = 0.027). Final LVEF in pigs receiving 10 mg empagliflozin was 51% (Q1-Q3: 46.5%-55.5%; P = 0.020 vs 20 mg empagliflozin). The incidence of AIC events was 0%, 50%, and 72% in the empagliflozin 20 mg, empagliflozin 10 mg, and doxorubicin control groups, respectively. Empagliflozin 20 mg treatment resulted in enhanced ketone body consumption by the myocardium, preserved magnetic resonance spectroscopy-measured cardiac energetics, and improved mitochondrial structure and function on transmission electron microscopy and respirometry. These changes were more modest with the 10-mg empagliflozin dose. CONCLUSIONS: Sodium-glucose cotransporter-2 inhibitor therapy with empagliflozin exerts a dose-dependent cardioprotective effect against AIC. The improved LVEF was accompanied by enhanced ketone body consumption, improved cardiac energetics, and preserved mitochondrial structure and function.

IMPORTANCE: Patients with angina and no obstructive coronary artery disease frequently have coronary vasomotor dysfunction as underlying pathophysiological mechanism, comprising epicardial spasm, microvascular spasm, and/or microcirculatory dysfunction. These endotypes can be diagnosed by invasive coronary function testing which has previously shown to be safe in tertiary and expert centers. OBJECTIVE: To determine the prevalence of vasomotor dysfunction in patients with angina and no obstructive coronary artery disease who were clinically referred for a coronary function test (CFT); and assess safety and feasibility of a CFT. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was performed using the Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT), a prospective, observational registry, in 15 participating hospitals (2 tertiary and 13 nontertiary). Patients with angina and no obstructive coronary artery disease who were referred for a clinically indicated CFT between December 2020 and January 2024 were included. MAIN OUTCOMES AND MEASURES: A complete CFT consisted of acetylcholine spasm provocation testing and assessment of microcirculatory function. Prevalence of different endotypes based on test results and overall safety were assessed. RESULTS: Among a total of 1207 patients included, 978 (81%) were female; and the mean (SD) age was 60 (10) years. The prevalence of coronary vasomotor dysfunction was very high (78%). There were 11 (0.9%) major and 10 (0.8%) minor complications reported. Of them, 3 major and all minor were definitely related to the coronary function test. No procedural death, myocardial infarction, or stroke was observed. No differences were found in the occurrence of complications between tertiary and nontertiary centers. CONCLUSIONS AND RELEVANCE: This study found that a CFT was feasible and safe to perform in both tertiary and nontertiary centers with a high diagnostic yield.