Oxidation-reduction imaging of myoglobin reveals two-phase oxidation in the reperfused myocardium.

Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation-reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation-reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia-reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation-reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.

Comparison of healthcare costs before and after a STEMI: A French national health data system-based cohort study.

BACKGROUND: Few studies have investigated real-world healthcare costs following a myocardial infarction (MI) and, to our knowledge, none after an ST-elevation MI (STEMI) specifically. Producing such data is important in order to help evaluate the economic burden of STEMI, but also to feed economic evaluation models and eventually show the economic interest of reducing STEMI incidence. The aim of this study was to estimate the healthcare cost in the year preceding and the year following a STEMI in France, in order to estimate the surplus in healthcare resource consumption after a STEMI. METHODS: This study was conducted from the healthcare system perspective. The individual data from the HIBISCUS-STEMI cohort, which included patients with acute STEMI undergoing primary percutaneous coronary intervention, were matched with the French national health data system (Système National des Données de Santé, SNDS) using a probabilistic method. All expenses (in- and out-hospital) presented for reimbursement were taken into account to estimate a mean annual healthcare cost. RESULTS: A total 258 patients from the HIBISCUS-STEMI cohort were included in this economic study. The total mean healthcare cost was estimated at €3516 before the STEMI, and at €9980 after the STEMI. Hospitalizations constituted the largest cost item, 27 % of the total cost before the STEMI and 41.8 % after the STEMI (Δ + 338.8 %). Follow-up and rehabilitative care represented the second largest cost item (25.9 % before and 18 % after the STEMI, Δ + 96.7 %). Treatments represented 19.4 % of the total cost before the STEMI and 17.2 % after (Δ + 150.8 %). CONCLUSIONS: This study shows a significant surplus (threefold) of healthcare resource consumption in the year following a STEMI compared to the year preceding the STEMI.

An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. DESIGN: Open-label, phase 2 study. PARTICIPANTS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). INTERVENTION: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). MAIN OUTCOMES: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. CONCLUSION: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover.

Deleterious Anti-Inflammatory Macrophage Recruitment in Early Post-Infarction Phase: Unraveling the IL-6/MCP-1/STAT3 Axis.

Using a translational approach with an ST-segment myocardial infarction (STEMI) cohort and mouse model of myocardial infarction, we highlighted the role of the secreted IL-6 and MCP-1 cytokines and the STAT3 pathway in heart macrophage recruitment and activation. Cardiac myocytes secrete IL-6 and MCP-1 in response to hypoxic stress, leading to a recruitment and/or polarization of anti-inflammatory macrophages via the STAT3 pathway. In our preclinical model of myocardial infarction, neutralization of IL-6 and MCP-1 or STAT3 pathway reduced infarct size. Together, our data demonstrate that anti-inflammatory macrophages can be deleterious in the acute phase of STEMI.

What underlies sex differences in heart failure onset within the first year after a first myocardial infarction?

Background: Women are more likely to develop heart failure (HF) after myocardial infarction. However, diagnosis and reperfusion are often delayed. Objectives: To compare the prevalence of HF after primary percutaneous coronary intervention (PPCI)-treated ST segment myocardial infarction (STEMI) between sexes and to study its associations with comorbidities, infarct size, and left ventricular (LV) systolic and diastolic dysfunctions (DD). Methods: The patients with PPCI-treated anterior STEMI, from the CIRCUS study cohort, were followed up for 1 year and HF events were recorded. Evaluation of ejection fraction (LVEF) and DD were performed at baseline and at 1 year. The elevated LV filling pressure (LVFP) included Grades 2 and 3 DD. Results: Of the 791 patients from the CIRCUS study, 135 were women. At 1 year, the proportion of patients who developed HF was 21% among men and 34% among women (p = 0.001). In the subset of 407 patients with available diastolic parameters, the rate of HF was also higher in women. HF during the initial hospitalization was comparable between the sexes. However, women had a higher incidence of rehospitalization for HF within the first year after STEMI (14.1% vs. 4.1%, p = 0.005). Women were older with a higher prevalence of hypertension. The infarct size and LVEF were similar between the sexes. Elevated LVFP was observed more frequently in women than in men during the initial hospitalization and at 1 year (26% vs. 12%, p = 0.04, and 22% vs. 12%, p = 0.006, respectively). Interestingly, only initial elevated LVFP (HR 5.9, 95% CI: 2.4-14.5, p < 0.001), age, and hypertension were independently associated with rehospitalization for HF. Conclusions: After PPCI-treated anterior STEMI, despite comparable infarct size and LVEF, women presented a higher proportion of rehospitalization for HF than men. That was likely due to a greater DD associated with older age and hypertension.