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.

Silent myocardial infarction fatty scars detected by coronary calcium score CT scan in diabetic patients without history of coronary heart disease.

OBJECTIVES: To evaluate the prevalence of intra-myocardial fatty scars (IMFS) most likely indicating previous silent myocardial infarction (SMI), as detected on coronary artery calcium (CAC) computed tomography (CT) scans in diabetic patients without history of coronary heart disease (CHD). METHODS: Diabetic patients screened for silent coronary insufficiency in a tertiary-care, university hospital between Jan-2015 and Dec-2016 were categorized according to their CAC score in two groups comprising 242 patients with CACS = 0 and 145 patients with CACS ≥ 300. CAC-CT scans were retrospectively evaluated for subendorcardial and transmural IMFS of the left ventricle. Adipose remodeling, patients' characteristics, cardiovascular risk factors and metabolic profile were compared between groups. RESULTS: Eighty-three (21%) patients with IMFS were identified, 55 (37.9%) in the group CACS ≥ 300 and 28 (11.6%) in the CACS = 0 (OR = 4.67; 95% CI = 2.78-7.84; p < 0.001). Total and average surface of IMFS and their number per patient were similar in both groups (p = 0.55; p = 0.29; p = 0.61, respectively). In the group CACS ≥ 300, patients with IMFS were older (p = 0.03) and had longer-lasting diabetes (p = 0.04). Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, more coronary calcifications (all p < 0.05), and higher prevalence of carotid plaques (OR = 3.03; 95% CI = 1.43-6.39, p = 0.004). After correction for other variables, only a CACS ≥ 300 (OR = 5.12; 95% CI = 2.66-9.85; p < 0.001) was associated with an increased risk of having IMFS. CONCLUSIONS: In diabetic patients without known CHD, IMFSs were found in patients without coronary calcifications, although not as frequently as in patients with heavily calcified coronary arteries. It remains to be established if this marker translates in an upwards cardiovascular risk restratification especially in diabetic patients with CACS = 0. CLINICAL RELEVANCE STATEMENT: In diabetic patients without history of coronary heart disease, intramyocardial fatty scars, presumably of post-infarction origin, can be detected on coronary artery calcium CT scans more frequently, but not exclusively, if the coronary arteries are heavily calcified as compared to those without calcifications. KEY POINTS: • Intramyocardial fatty scars (IMFS), presumably of post-infarction origin, can be detected on coronary artery calcium (CAC) CT scans more frequently, but not exclusively, in diabetic patients with CACS ≥ 300 as compared to patients CACS = 0. • Patients with IMFS were older and had longer history of diabetes, reduced glomerular filtration rate, and more coronary calcifications. • Carotid plaques and CACS ≥ 300 were associated with an increased risk of having IMFS, about three and five folds respectively.

Prognostic impact of precipitated cardiac decompensation in symptomatic heart failure with reduced ejection fraction and severe secondary mitral regurgitation.

BACKGROUND: Our aim was to assess the distribution of primary (with no trigger) and secondary (with a decompensation trigger) heart failure events in a severe heart failure population and their association with 2-year all-cause mortality in the Mitra.Fr study. METHODS: We included 304 patients with symptomatic heart failure, and severe mitral regurgitation and guideline directed medical therapy randomized to medical therapy alone or medical therapy with percutaneous mitral valve repair. According to the follow-up, we defined 3 categories of events: follow-up without any heart failure event, at least 1 decompensation starting with a primary heart failure decompensation or starting with a precipitated secondary heart failure event. The primary outcome was 2-years all-cause mortality. RESULTS: A total of 179 patients (59 %) had at least 1 heart failure decompensation within 24-months of follow-up. 129 heart failure decompensations (72%) were a first primary heart failure and 50 (28%) were a first secondary decompensation. Finally, 30 patients had both types of decompensations but these were not taken into account for the comparison of primary and secondary decompensations. Primary decompensations were 3-times more frequent than secondary decompensations, but the mean number of heart failure decompensations was similar in the "Primary heart failure group" compared to the "Secondary heart failure group": (1.94 ± 1.39 vs 1.80 ± 1.07 respectively; P = .480). Compared to patients without heart failure decompensation, patients with "Only primary decompensation" or with "Only secondary decompensation" had a significantly increased risk of death (HR = 4.87, 95% CI [2.86, 8.32] and 2.68 95%CI [1.64, 4.37] respectively). All-cause mortality, was not significantly different between these 2 type of decompensations (HR = 1.82, 95% CI [0.93, 3.58]; P = .082), but each additional heart failure recurrence was associated with a significant increase in mortality risk (HR = 1.27, 95% CI [1.08; 1.50]; P = .005). CONCLUSIONS: In heart failure with reduced ejection fraction and severe secondary mitral regurgitation patients, primary heart failure decompensations were 3-times more frequent compared to precipitated decompensations with a nonsignificant trend in increased risk of all-cause mortality. Our results fail to support the differentiation between primary and secondary decompensations as they seem to portend the same outcome impact.

A Multimodal Cardioprotection Strategy During Cardiac Surgery: The ProCCard Study.

OBJECTIVE: The ProCCard study tested whether combining several cardioprotective interventions would reduce the myocardial and other biological and clinical damage in patients undergoing cardiac surgery. DESIGN: Prospective, randomized, controlled trial. SETTING: Multicenter tertiary care hospitals. PARTICIPANTS: 210 patients scheduled to undergo aortic valve surgery. INTERVENTIONS: A control group (standard of care) was compared to a treated group combining five perioperative cardioprotective techniques: anesthesia with sevoflurane, remote ischemic preconditioning, close intraoperative blood glucose control, moderate respiratory acidosis (pH 7.30) just before aortic unclamping (concept of the "pH paradox"), and gentle reperfusion just after aortic unclamping. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the postoperative 72-h area under the curve (AUC) for high-sensitivity cardiac troponin I (hsTnI). Secondary endpoints were biological markers and clinical events occurring during the 30 postoperative days and the prespecified subgroup analyses. The linear relationship between the 72-h AUC for hsTnI and aortic clamping time, significant in both groups (p < 0.0001), was not modified by the treatment (p = 0.57). The rate of adverse events at 30 days was identical. A non-significant reduction of the 72-h AUC for hsTnI (-24%, p = 0.15) was observed when sevoflurane was administered during cardiopulmonary bypass (46% of patients in the treated group). The incidence of postoperative renal failure was not reduced (p = 0.104). CONCLUSION: This multimodal cardioprotection has not demonstrated any biological or clinical benefit during cardiac surgery. The cardio- and reno-protective effects of sevoflurane and remote ischemic preconditioning therefore remain to be demonstrated in this context.

Challenges and Opportunities in Titrating Disease-Modifying Therapies in Heart Failure with Reduced Ejection Fraction and Chronic Kidney Disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is highly prevalent in patients with heart failure and reduced ejection fraction (HFrEF), representing a major factor of adverse outcomes. In clinical practice, it is one of the main reasons for not initiating, not titrating, and even withdrawing efficient heart failure drug therapies in patients. RECENT FINDINGS: Despite limited data, studies show that HFrEF therapies maintain their benefits on cardiovascular outcomes in patients with CKD. Most HF drugs cause acute renal haemodynamic changes, but with stabilisation or even improvement after the acute phase, thus with no long-term worsening of the renal function. In this expert opinion-based paper, we challenge the pathophysiology misunderstandings that impede HF disease-modifying therapy implementation in this setting and propose a strategy for HF drug titration in patients with moderate, severe, and end-stage chronic kidney disease.

Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction.

BACKGROUND: Inflammation is a key factor of myocardial damage in reperfused ST-segment-elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment-elevation myocardial infarction. METHODS: In this double-blind multicenter trial, we randomly assigned patients admitted for a first episode of ST-segment-elevation myocardial infarction referred for primary percutaneous coronary intervention to receive oral colchicine (2-mg loading dose followed by 0.5 mg twice a day) or matching placebo from admission to day 5. The primary efficacy outcome was IS determined by cardiac magnetic resonance imaging at 5 days. The relative LV end-diastolic volume change at 3 months and IS at 3 months assessed by cardiac magnetic resonance imaging were among the secondary outcomes. RESULTS: We enrolled 192 patients, 101 in the colchicine group and 91 in the control group. At 5 days, the gadolinium enhancement-defined IS did not differ between the colchicine and placebo groups with a mean of 26 interquartile range (IQR) [16-44] versus 28.4 IQR [14-40] g of LV mass, respectively (P=0.87). At 3 months follow-up, there was no significant difference in LV remodeling between the colchicine and placebo groups with a +2.4% (IQR, -8.3% to 11.1%) versus -1.1% (IQR, -8.0% to 9.9%) change in LV end-diastolic volume (P=0.49). Infarct size at 3 months was also not significantly different between the colchicine and placebo groups (17 IQR [10-28] versus 18 IQR [10-27] g of LV mass, respectively; P=0.92). The incidence of gastrointestinal adverse events during the treatment period was greater with colchicine than with placebo (34% versus 11%, respectively; P=0.0002). CONCLUSIONS: In this randomized, placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days did not reduce IS assessed by cardiac magnetic resonance imaging. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03156816.

Impact of Age on Systemic Inflammatory Profile of Patients With ST-Segment-Elevation Myocardial Infarction and Acute Ischemic Stroke.

BACKGROUND: Aging is associated with a chronic low-grade inflammatory state. This condition may affect the acute inflammatory response involved in ST-segment-elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS). We sought to compare the profile of a set of circulating inflammatory markers between young and older patients admitted for STEMI or AIS. METHODS: HIBISCUS-STEMI (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in ST Elevation Myocardial Infarction) and HIBISCUS-STROKE (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke) are 2 cohort studies that enrolled patients with STEMI treated with primary percutaneous coronary intervention in the cardiac intensive care unit of Lyon and patients with AIS treated with mechanical thrombectomy in the Lyon Stroke Center, respectively from 2016 to 2019. Patients were classified as older if they were ≥65 years and as young if they were <65 years. In both cohorts, CRP (C-reactive protein), IL (interleukin)-6, IL-8, IL-10, MCP (monocyte chemoattractant protein), sTNF-RI (soluble tumor necrosis factor receptor I), sST2 (soluble form suppression of tumorigenicity 2), and VCAM-1 (vascular cellular adhesion molecule-1) were measured on serum collected at 5 time points using enzyme-linked immunosorbent assay. A multiple logistic regression model was performed to detect an association between area under the curve of circulating inflammatory markers within the first 48 hours and older age. RESULTS: A total of 260 patients with STEMI and 164 patients with AIS were included. Of them, there were 76 (29%) and 105 (64%) older patients with STEMI and AIS, respectively. Following multivariable analysis, a high area under the curve of IL-6 and sTNF-RI, a low lymphocyte count, and a high neutrophil-lymphocyte ratio at 24 hours were associated with older age in patients with STEMI and AIS. CONCLUSIONS: Older patients had higher IL-6 and sTFN-RI levels within the first 48 hours associated with a lower lymphocyte count and a higher neutrophil-lymphocyte ratio at 24 hours in both cohorts.

Ventricular septal rupture: insights into an old disease.

Ventricular septal rupture (VSR) is a serious complication of ST-elevation myocardial infarction (STEMI) and surgery is the reference treatment. We aimed at describing trends in management and mortality during the last four decades and reporting mortality predictors in these patients. We conducted a single-center retrospective study of patients sustaining a VSR from 1981 to 2020. We screened 274 patients and included 265 for analysis. The number of patients decreased over the years: 80, 88, 56, and 50 in each 10-year time span. In-hospital mortality decreased significantly since 1990 (logrank 0.007). The median age was 72.0 years IQR [66-78] and 188 patients (70.9%) were operated on. IABP was used more routinely (p < 0.0001). In-hospital mortality was assessed at 66.8% (177 patients) and main predictors of death were a time from MI to surgery < 8 days HR 2.7 IC95% [1.9-3.8] p < 0.0001, a Killip class > 2 HR 2.5 IC [1.9-3.4] p < 0.0001 and Euroscore 2 > 20 HR 2.4 IC [1.8-3.2] p < 0.0001. A "time from MI to surgery" of 8 days offers the best ability to discriminate between patients with or without mortality. The ability of "Euroscore 2 and Killip" to detect the patients most likely to wait 8 days for surgery was at 0.81 [0.73-0.89] p < 0.0001. Mortality remains high over the years. Euroscore 2, Killip class, and time from MI to surgery are the main mortality predictors. Patients with a Killip < 3 and a Euroscore < 20 should be monitored at least 8 days since MI before being referred to surgery.

Clinical characteristics and outcome of elderly patients admitted in emergency department with an oxygen mismatch and type 2 myocardial infarction or myocardial injury.

BACKGROUND: Aging is a risk factor for type 2 myocardial infarction or myocardial injury, but few data are available on the elderly. We aimed to determine the factors associated with these pathologies and mortality in the elderly population and its age classes. METHODS: A retrospective cohort of all patients with oxygen mismatch (anemia, hypoxia, tachycardia, hypo/hypertension) for whom a troponin drawn was performed at admission in 2 emergency departments. Medical records were reviewed and classified as having type 2 myocardial infarction, acute or chronic myocardial injury, or no myocardial injury. RESULTS: Of the 824 patients who presented with oxygen mismatch, 675 (81.9%) were older than 65 years. Age over 85 years was a risk factor for acute non-ischemic myocardial injury (odds ratio, 95% confidence interval 2.23, 1.34-3.73). Non-ischemic myocardial injury was associated with hypoxemia, tachycardia, and acute renal failure in those older than 85 years, but only with acute infection in the 75-84-year-old group. Type 2 myocardial infarction was associated only with acute renal failure in the oldest group and, in the 75-84-year-old group, with acute heart failure and shock. Patients older than 85 years with acute myocardial injury, with or without infarction, had a higher in-hospital mortality, but subsequently, mortality depends more on the comorbidities than on age. CONCLUSION: Factors associated with type 2 myocardial infarction and acute non-ischemic myocardial injury in elderly admitted with oxygen mismatch vary notably between age classes. They are associated with in-hospital mortality but not with subsequent mortality when other cormorbities are taken into account.

Regression of Q waves and clinical outcomes following primary PCI in anterior STEMI.

BACKGROUND: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after reperfusion with clinical outcomes after anterior STEMI. METHODS: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had regression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year. RESULTS: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave regression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 ±â€¯2784 IU/l vs. 3814 ±â€¯2595 IU/l vs. 1733 ±â€¯1583 IU/l respectively, p < 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09). CONCLUSION: In a population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.

Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation.

BACKGROUND: In patients who have chronic heart failure with reduced left ventricular ejection fraction, severe secondary mitral-valve regurgitation is associated with a poor prognosis. Whether percutaneous mitral-valve repair improves clinical outcomes in this patient population is unknown. METHODS: We randomly assigned patients who had severe secondary mitral regurgitation (defined as an effective regurgitant orifice area of >20 mm2 or a regurgitant volume of >30 ml per beat), a left ventricular ejection fraction between 15 and 40%, and symptomatic heart failure, in a 1:1 ratio, to undergo percutaneous mitral-valve repair in addition to receiving medical therapy (intervention group; 152 patients) or to receive medical therapy alone (control group; 152 patients). The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months. RESULTS: At 12 months, the rate of the primary outcome was 54.6% (83 of 152 patients) in the intervention group and 51.3% (78 of 152 patients) in the control group (odds ratio, 1.16; 95% confidence interval [CI], 0.73 to 1.84; P=0.53). The rate of death from any cause was 24.3% (37 of 152 patients) in the intervention group and 22.4% (34 of 152 patients) in the control group (hazard ratio, 1.11; 95% CI, 0.69 to 1.77). The rate of unplanned hospitalization for heart failure was 48.7% (74 of 152 patients) in the intervention group and 47.4% (72 of 152 patients) in the control group (hazard ratio, 1.13; 95% CI, 0.81 to 1.56). CONCLUSIONS: Among patients with severe secondary mitral regurgitation, the rate of death or unplanned hospitalization for heart failure at 1 year did not differ significantly between patients who underwent percutaneous mitral-valve repair in addition to receiving medical therapy and those who received medical therapy alone. (Funded by the French Ministry of Health and Research National Program and Abbott Vascular; MITRA-FR ClinicalTrials.gov number, NCT01920698 .).

Nonculprit Artery Myocardial Infarction and Complex Coronary Lesions in Anterior ST-Elevated Myocardial Infarction Patients: Data from the CIRCUS Study.

AIMS: Periprocedural myocardial infarctions have been reported in the setting of planned percutaneous coronary intervention (PCI). We assessed the prevalence of nonculprit artery acute myocardial infarction (NCAMI) and its relationship with coronary artery characteristics, final infarct size, and 1-year adverse clinical outcomes in a population of anterior ST-elevated myocardial infarction (STEMI) patients. METHODS AND RESULTS: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) studies were performed within 7 days of admission in 129 anterior STEMI patients from the CIRCUS trial treated by primary PCI. Infarct in the noninfarct artery territory (circumflex, right coronary) was assessed on LGE-CMR and T2-weighted images. Eleven (8.5%) patients exhibited NCAMI. The only independent characteristic significantly associated with NCAMI was the presence of multiple complex coronary lesions (odds ratio = 12.9, 95% confidence interval [3.1-53.4]; p < 0.001). There was a significantly increased infarct size in NCAMI patients compared to patients without NCAMI (45.8 ± 20.4% of the left ventricle [LV] vs. 31.0 ± 15.1% of LV, respectively; p = 0.02), with lower LV ejection fraction (46 ± 10% vs. 34 ± 8%, respectively; p < 0.001). CONCLUSION: NCAMIs are present in 8.5% of anterior STEMI patients and are significantly associated with multiple complex coronary lesions without significant relationship to any revascularization procedural technique. NCAMI was associated with a greater infarct size and reduced LVEF but not worse clinical outcomes at 1 year.

Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol - The COVERT-MI Study.

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.

Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion.

BACKGROUND AND PURPOSE: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. METHODS: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0-2) and good (Higashida score, 3-4). A multiple logistic regression model was performed to detect independent markers of good collateral status. RESULTS: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels (P=0.01), high MCP-1 levels (P<0.01), a low National Institute of Health Stroke Score (P=0.046), a high diastolic blood pressure (P=0.049), the absence of tandem occlusion (P=0.046), a high Alberta Stroke Program Early CT Score (P<0.01) and a low volume on the diffusion-weighted imaging (P<0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels (P=0.02) and high MCP-1 levels (P<0.01) remained associated with good collateral status. CONCLUSIONS: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.

MRI of Reperfused Acute Myocardial Infarction Edema: ADC Quantification versus T1 and T2 Mapping.

Background After acute myocardial infarction (AMI), reperfusion injury is associated with microvascular lesions and myocardial edema. Purpose To evaluate the performance of apparent diffusion coefficient (ADC) quantification compared with T1 and T2 values in the detection of acute myocardial injury. Materials and Methods In this prospective study conducted from June 2016 to November 2018, participants without a history of heart failure or cardiomyopathy were enrolled after undergoing reperfusion for their first AMI. Quantitative T1 and T2 mapping were performed with a 1.5-T MRI scanner and compared with a fast free-breathing acquisition technique for ADC mapping (approximate duration, 3 minutes; five slices; spin-echo cardiac diffusion acquisition; b values, 0 and 200 sec/mm2; six diffusion-encoding directions; five repetitions). Quantitative ADC and unenhanced T1 and T2 values were compared in infarct, border, and remote regions by using Welch analysis of variance with Games-Howell post hoc test for pairwise comparisons. Results Thirty-four participants with AMI underwent MRI an average of 5 days ± 1.9 (standard deviation) after reperfusion. Mean ADC was markedly high in the infarcted regions (2.32 × 10-3 mm2/sec; 95% confidence interval [CI]: 2.28, 2.36) and moderately high in the border regions (1.91 ×10-3 mm2/sec; 95% CI: 1.89, 1.94; P < .001). In remote regions, mean ADC (1.62 ×10-3 mm2/sec; 95% CI: 1.59, 1.64) was comparable to that measured in vivo in healthy volunteers. Within the same regions of interest, although the measures showed similar trends in infarct and remote regions for T1 (mean, 1332 mec [95% CI: 1296, 1368] vs 1045 msec [95% CI: 1034, 1056]; P < .001) and T2 (72 msec [95% CI: 69, 75] vs 50 msec [95% CI: 49, 51]; P < .001), the magnitude of the differences among regions was greater when using ADC. Normalized signal differences between infarct and remote regions showed that diffusion-weighted MRI depicted edema 5.1 (P < .001) and 3.5 (P < .001) times greater than did T1 and T2 maps, respectively. Conclusion Multislice cardiac diffusion-weighted images could be acquired in those with acute myocardial injury. Quantitative apparent diffusion coefficient mapping showed greater differences among remote regions and lesions than did T1 or T2 mapping. © RSNA, 2020 See also the editorial by Lloyd and Farris in this issue.

Myocardial infarction: Economic, health, and social impacts on informal caregivers.

OBJECTIVES: The aim of the study was to measure the economic impact of informal care (IC) on caregivers assisting myocardial infarction (MI) survivors in France. Health and social impacts were also described. METHODS: Data from the prospective 2008 Health and Disabilities Households Survey (Enquête Handicap-Santé), carried out among the French general population, were used to obtain information about patients with MI and their informal caregivers. To estimate the approximate monetary value of IC, three methods were used: the proxy good method, opportunity cost method (OCM), and contingent valuation method (CVM). A multivariate analysis was performed to determine the associations of the IC duration and the existence of professional care with the health indicators stated by caregivers. RESULTS: The analysis included data from 147 caregivers. The mean value of IC ranged from €9,679 per year using the CVM to €11,288 per year using the OCM (p > .05). The mean willingness to pay for an additional hour of IC was €10.9 (SD = 8.3). A total of 46.2 percent of caregivers reported that IC negatively affected theirs physical condition, and 46.3 percent reported that it negatively affected their psychological health. In addition, 40.1 percent declared that caregiving activity made them anxious and 38.8 percent stated they felt alone. Associations were identified between the duration of IC and feeling the need to be replaced, feeling alone and making sacrifices (p < .05). CONCLUSIONS: Informal caregiver burden may be recognized in health technology assessment in order not to underestimate the cost of strategies and to facilitate the comparability of cost-effectiveness outcomes between studies.

Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients.

Despite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit of a single intravenous bolus of cyclosporine in 969 patients with anterior STEMI. Since cyclosporine had no detectable effect on clinical outcomes as well as on any measured variable, we here considered the whole study population as one group. Multivariate analysis was performed to address the respective weight of infarct size and variables in clinical outcomes. Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year. The relative weight of infarct size and variables on the composite endpoint of [death or hospitalization for heart failure] at 1 year was 18% and 82%, respectively. Several variables contribute strongly to the clinical outcomes of STEMI patients suggesting that cardioprotective strategy might not only focus on infarct size reduction.