Rationale:: Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome are poorly understood. We have previously reported that neutrophil (polymorphonuclear cells [PMNs]) accumulation in culprit lesion site (CLS) thrombus is a predictor of cardiovascular outcomes. Objective:: The goal of this study was to characterize PMN activation at the CLS. We examined the relationships between CLS neutrophil extracellular traps (NETs), bacterial components as triggers of NETosis, activity of endogenous deoxyribonuclease, ST-segment resolution, and infarct size. Methods and Results:: We analyzed coronary thrombectomies from 111 patients with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Thrombi were characterized by immunostaining, flow cytometry, bacterial profiling, and immunometric and enzymatic assays. Compared with femoral PMNs, CLS PMNs were highly activated and formed aggregates with platelets. Nucleosomes, double-stranded DNA, neutrophil elastase, myeloperoxidase, and myeloid-related protein 8/14 were increased in CLS plasma, and NETs contributed to the scaffolds of particulate coronary thrombi. Copy numbers of Streptococcus species correlated positively with dsDNA. Thrombus NET burden correlated positively with infarct size and negatively with ST-segment resolution, whereas CLS deoxyribonuclease activity correlated negatively with infarct size and positively with ST-segment resolution. Recombinant deoxyribonuclease accelerated the lysis of coronary thrombi ex vivo. Conclusions:: PMNs are highly activated in ST-elevation acute coronary syndrome and undergo NETosis at the CLS. Coronary NET burden and deoxyribonuclease activity are predictors of ST-segment resolution and myocardial infarct size.

Background—: Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF. Methods and Results—: One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV ( R =0.494, P =0.037). Patients were followed for 24.0 months (6.0–32.0 months), during which 34 had a cardiac event. By Kaplan–Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank, P =0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide ( P <0.001), 6-minute walk distance ( P =0.004), New York Heart Association functional class ( P =0.009), right atrial pressure ( P =0.037), and stroke volume ( P =0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables ( P =0.038) but not after adjustment for clinical and invasive hemodynamic parameters. Conclusions—: We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.

Background: Men and women are labeled as obese on the basis of a body mass index (BMI) using the same criterion despite known differences in their fat distributions. Subcutaneous adipose tissue and visceral adipose tissue (VAT), as measured by computed tomography, are advanced measures of obesity that closely correlate with cardiometabolic risk independent of BMI. However, it remains unknown whether prognostic significance of anthropometric measures of adiposity versus VAT varies in men versus women. Methods and Results: In 3482 FHS (Framingham Heart Study) participants (48.1% women; mean age, 50.8±10.3 years), we tested the associations of computed tomography–based versus anthropometric measures of fat with cardiometabolic and cardiovascular disease (CVD) risk. Mean follow‐up was 12.7±2.1 years. In men, VAT, as compared with BMI, had a similar strength of association with incident cardiometabolic risk factors (eg, adjusted odds ratio [OR], 2.36 [95% CI, 1.84–3.04] versus 2.66 [95% CI, 2.04–3.47] for diabetes mellitus) and CVD events (eg, adjusted hazard ratio [HR], 1.32 [95% CI, 0.97–1.80] versus 1.74 [95% CI, 1.14–2.65] for CVD death). In women, however, VAT, when compared with BMI, conferred a markedly greater association with incident cardiometabolic risk factors (eg, adjusted OR, 4.51 [95% CI, 3.13–6.50] versus 2.33 [95% CI, 1.88–3.04] for diabetes mellitus) as well as CVD events (eg, adjusted HR, 1.85 [95% CI, 1.26–2.71] versus 1.19 [95% CI, 1.01–1.40] for CVD death). Conclusions: Anthropometric measures of obesity, including waist circumference and BMI, adequately capture VAT‐associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal computed tomography–based VAT measures permit more precise assessment of obesity‐associated cardiometabolic and cardiovascular risk.