Daily Cardiology Research Analysis

IMPORTANCE: Fluorescence lifetime imaging (FLIm) is a molecular imaging technique used to visualize the biochemical composition of atherosclerosis. Novel dual-modal imaging using optical coherence tomography (OCT)-FLIm has the potential to provide both microstructural and biocompositional information on coronary plaques; however, it needs validation for clinical application. OBJECTIVE: To investigate the clinical feasibility and safety of OCT-FLIm for characterizing plaque compositions in patients with coronary artery disease (CAD) undergoing revascularization therapy. DESIGN, SETTING, AND PARTICIPANTS: A prospective, open-label, single-center diagnostic feasibility study involving 40 patients with significant CAD requiring coronary revascularization. This first-in-human clinical study of the novel intracoronary OCT-FLIm imaging was conducted between February and August 2022. The analyses were performed from August 2022 to July 2023. INTERVENTIONS: An OCT-FLIm system with 2.6-F catheters was constructed. All patients underwent OCT-FLIm for target/culprit and nontarget/nonculprit lesions during coronary revascularization. Intravascular ultrasound imaging was performed for comparison. MAIN OUTCOMES AND MEASURES: The primary outcome was to assess the FLIm-derived molecular readouts of prespecified plaque compositions. The secondary outcome was the feasibility of OCT-FLIm in determining target/culprit plaque compositions across different subsets of atherosclerotic disease activity: (1) acute coronary syndrome (ACS) vs chronic stable angina (CSA) and (2) angiographic rapid disease progression vs nonprogressive controls. RESULTS: We prospectively enrolled 40 patients (mean [SD] age, 63.1 [8.1] years; 32 men [80.0%]), of whom 20 presented with ACS and 20 with CSA. OCT provided the structural features of plaques, and FLIm characterized the molecular signatures of atheroma compositions, including macrophages, healed plaques, superficial calcification, and fibrosis, in a reproducible manner. Fluorescence lifetime (FL) values of the plaque compositions correlated with findings from prior autopsy studies. Plaque inflammation was significantly greater in patients with ACS than those with CSA. The mean (SD) of inflammation-FL was 7.59 (0.96) nanoseconds for patients with ACS vs 6.46 (0.87) nanoseconds for patients with CSA (P < .001). The healed plaque phenotype was more prominently distributed in the segments of rapid disease progression than in nonprogressive controls. The mean (SD) healed plaque-FL was 5.31 (0.20) nanoseconds for the rapidly progressive lesions vs 4.81 (0.30) nanoseconds for the rapidly nonprogressive lesions (P < .001). All patients underwent OCT-FLIm safely without adverse clinical events. CONCLUSIONS AND RELEVANCE: This diagnostic feasibility study found that an OCT-FLIm structural-molecular intracoronary imaging is clinically feasible and safe for the comprehensive characterization of human atheromas, supporting its potential role in the diagnosis and biological understanding of high-risk plaques.

BACKGROUND AND AIMS: Ventricular tachycardia and ventricular fibrillation underlie many sudden cardiac deaths, but common lifestyle factors that predict their occurrence are poorly understood. This study aimed to assess the association between methamphetamine and cocaine, the most used illicit stimulants, and ventricular arrhythmias (VA) and mortality. METHODS: Healthcare databases were used to identify adults aged ≥ 18 years receiving hospital-based care in California in 2005-2019. ICD codes were used to identify diagnoses and illicit stimulant use. Cox proportional hazard models adjusting for demographics and time-updated cardiovascular risk factors were employed. The outcomes were VA combining ventricular tachycardia, ventricular fibrillation, and cardiac arrest and all-cause mortality. RESULTS: Among 29 593 819 individuals (53.8% female, mean age 44.9 years), 690 737 (2.3%) used methamphetamine, and 290 652 (1.0%) used cocaine at some point. After adjustment for age, sex, race and ethnicity, cannabis and opioid use, and other cardiovascular risk factors, methamphetamine use and cocaine use were each associated with increased risk of incident VA [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.85-1.95, and HR 1.15, 95% CI 1.10-1.19, respectively], and mortality (HR 1.51, 95% CI 1.47-1.54 and HR 1.68, 95% CI 1.64-1.72, respectively). The risk of VA was higher in younger individuals (<65 years) and females for both methamphetamine and cocaine, whereas it was higher in Blacks and lower in Whites and Hispanics for cocaine use, and higher in Asians and lower in Blacks for methamphetamine use (P for interaction < .05 in all). CONCLUSIONS: Methamphetamine use and cocaine use were each associated with increased risk of incident VA and mortality, with differential relationships by demographic groups. Avoiding these substances may reduce risk of VA and death.

IMPORTANCE: Innate immunity, particularly neutrophil activation, plays a crucial role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). The potential of calprotectin, a biomarker of neutrophil activation, as a mechanistically informed biomarker for ASCVD in an ethnically diverse population requires further investigation. OBJECTIVE: To examine the prospective association between circulating calprotectin and ASCVD in a diverse, population-based cohort while also exploring calprotectin's mechanistic contributions to ASCVD in vitro. DESIGN, SETTING, AND PARTICIPANTS: Circulating calprotectin was measured in plasma collected from 2412 participants during phase 2 of the Dallas Heart Study, a multiethnic, population-based cohort study. The median follow-up after plasma collection was 8 years. MAIN OUTCOMES AND MEASURES: Associations with future ASCVD events (defined as first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or death from a cardiovascular cause) were assessed using Cox proportional hazards models, adjusted for known cardiovascular disease risk factors as well as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: Higher calprotectin levels were associated with older age, male sex, Black race, hypertension, diabetes, and smoking history. Individuals with higher calprotectin had higher hemoglobin A1c, very low-density lipoprotein cholesterol, and triglycerides, and lower high-density lipoprotein cholesterol and cholesterol efflux capacity. Log-transformed calprotectin levels were associated with an increased risk of ASCVD events over 8 years (hazard ratio [HR], 1.98 per log increase [95% CI, 1.54-2.53]). This association remained statistically significant after adjusting for prior ASCVD and traditional risk factors (HR, 1.61 [95% CI, 1.22-2.13]) and hs-CRP, NT-proBNP, and hs-cTnT (HR, 1.43 [95% CI, 1.04-1.96]). Higher calprotectin also correlated with higher coronary artery calcium scores (P < .001). In vitro studies revealed that calprotectin impaired coronary endothelial integrity, diminished nitric oxide production, and fostered endothelial to mesenchymal transition, providing potential mechanisms for ASCVD progression. CONCLUSIONS AND RELEVANCE: The findings suggest that calprotectin may serve as a mechanistically informed biomarker for ASCVD, independent of traditional and contemporary cardiovascular risk factors and biomarkers. However, its clinical utility warrants further evaluation.