Colchicine in acute myocardial infarction: cardiovascular events at 1-year follow up.

OBJECTIVE: In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population. METHODS: This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed. RESULTS: At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18). CONCLUSIONS: There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group. TRIAL REGISTRATION NUMBER: NCT0315681.

Specific inflammatory profile of acute ischemic stroke patients with left atrial enlargement.

Background: The inflammatory process underlying atrial myopathy may affect the inflammatory response activated in acute ischemic stroke (AIS). Objectives: We aimed to assess whether left atrial enlargement (LAE) as a marker of atrial myopathy is associated with a different profile of circulating inflammatory markers in AIS patients. Methods: HIBISCUS-STROKE is a cohort study including anterior circulation AIS patients treated with mechanical thrombectomy following MRI. Ten circulating inflammatory markers were measured at admission and 6, 24, and 48 h after admission. LAE was defined as a left atrial volume index (LAVi) ≥34 ml/m2. A multiple logistic regression model was performed to detect an independent association between the area under the curve (AUC) of these markers and LAE. Results: We included 143 patients. Of them, 85 (59.4%) had LAE. On univariable analysis, we found that patients with LAE had higher soluble form suppression of tumorigenicity 2 (sST2), soluble tumor necrosis factor receptor I (sTNFR1), and vascular cellular adhesion molecule-1 (VCAM-1) AUC, were older, mostly female, had a higher National Institutes of Health Stroke Scale (NIHSS) score and blood glucose level at admission, had more often hypertension, and a cardioembolic source of AIS, such as atrial fibrillation, while they were less frequently current smokers and had a lower rate of tandem occlusion than patients without LAE. On multivariable analysis, we found that among circulating inflammatory markers, only high VCAM-1 (OR: 9.13, 95% CI: 3.21-25.9) and sST2 (OR: 3.40, 95% CI: 1.68-6.86) AUC remained associated with LAE. Conclusions: High VCAM-1 and sST2 levels within the first 48 h are associated with LAE in AIS patients.

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.

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.

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.

Prognosis value of serum soluble ST2 level in acute ischemic stroke and STEMI patients in the era of mechanical reperfusion therapy.

BACKGROUND: Soluble form suppression of tumorigenicity 2 (sST2) is known to have prognostic value in ST-elevation myocardial infarction (STEMI) and could impact mortality after acute ischemic stroke (AIS). However, before considering sST2 as a therapeutic target, the kinetics of release and its association with adverse clinical events in both STEMI and AIS patients have to be determined. METHODS: We prospectively enrolled 251 STEMI patients, treated with primary percutaneous coronary intervention, and 152 AIS patients treated with mechanical thrombectomy. We evaluated the level of sST2 in patient sera at five time point (admission, 4, 24, 48 h and 1 month from admission for STEMI patients and admission, 6, 24, 48 h and 3 months from admission for AIS patients). Major adverse clinical events (MACE) (all-cause death, acute myocardial infarction, stroke or hospitalization for heart failure) in STEMI patients and all-cause death in AIS patients were recorded during a 12-month follow-up. RESULTS: Mean age of the study population was 59 ± 12 and 69 ± 15 years in STEMI and AIS patients, respectively. In STEMI patients, sST2 peaked 24 h after admission (25.5 ng/mL interquartile range (IQR) [14.9-29.1]) whereas an earlier and lower peak was observed in AIS patients (16.8 ng/mL IQR [15.2-18.3] at 6 h). Twenty-five (10.0%) STEMI patients experienced a MACE and 12 (7.9%) AIS patients had all-cause death within the first 12 months. A high level of sST2 at 24 h was associated with MACE in STEMI patients (hazard ratio (HR) = 2.5; 95% confidence interval (CI) [1.1-5.6], p = 0.03) and all-cause death in AIS patients (HR = 11.7; 95% CI [3.8-36.2], p < 0.01) within the first 12 months. CONCLUSIONS: The study highlights that sST2 levels at 24 h are associated with an increased risk to adverse clinical events in both diseases.

Serum Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Early Prognosis Markers After ST-Segment Elevation Myocardial Infarction.

Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity. Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outcomes in STEMI patients. Methods: We enrolled into a prospective cohort 251 consecutive STEMI patients referred to our hospital for percutaneous coronary intervention revascularization. Blood samples were collected at five time points: admission and 4, 24, 48 h, and 1 month after admission to assess sTNFR1 and sTNFR2 serum concentrations. Patients underwent cardiac magnetic resonance imaging at 1 month. Results: sTNFR1 concentration increased at 24 h with a median of 580.5 pg/ml [95% confidence interval (CI): 534.4-645.6]. sTNFR2 increased at 48 h with a median of 2,244.0 pg/ml [95% CI: 2090.0-2,399.0]. Both sTNFR1 and sTNFR2 peak levels were correlated with infarct size and left ventricular end-diastolic volume and inversely correlated with left ventricular ejection fraction. Patients with sTNFR1 or sTNFR2 concentration above the median value were more likely to experience an adverse clinical event within 24 months after STEMI [hazards ratio (HR): 8.8, 95% CI: 4.2-18.6, p < 0.0001 for sTNFR1; HR: 6.1, 95% CI: 2.5 -10.5, p = 0.0003 for sTNFR2]. Soluble TNFR1 was an independent predictor of major adverse cardiovascular events and was more powerful than troponin I (p = 0.04 as compared to the troponin AUC). Conclusion: The circulating sTNFR1 and sTNFR2 are inflammatory markers of morphological and functional injury after STEMI. sTNFR1 appears as an early independent predictor of clinical outcomes in STEMI patients.

Kinetics and prognostic value of soluble VCAM-1 in ST-segment elevation myocardial infarction patients.

BACKGROUND: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker of endothelial activation and inflammation. There is still controversy as to whether it can predict clinical outcome after ST-elevation myocardial infarction (STEMI). Our aim was to assess the sVCAM-1 kinetics and to evaluate its prognostic predictive value. METHOD: We prospectively enrolled 251 consecutive STEMI patients who underwent coronary revascularization in our university hospital. Blood samples were collected at admission, 4, 24, 48 h and 1 month after admission. sVCAM-1 serum level was assessed using ELISA assay. All patients had cardiac magnetic resonance imaging at 1-month for infarct size (IS) and left ventricular ejection fraction (LVEF) assessment. Clinical outcomes were recorded over 12 months after STEMI. RESULTS: sVCAM-1 levels significantly increased from admission up to 1 month and were significantly correlated with IS, LVEF, and LV end-systolic and diastolic volume. (H48 area under curve (AUC) ≥ H48 median) were associated with an increased risk of adverse clinical events during the 12-month follow-up period with a hazard ratio (HR) = 2.6 (95% confidence interval [CI] of ratio = 1.2-5.6, p = .02). The ability of H48 AUC for sVCAM-1 to discriminate between patients with or without the composite endpoint was evaluated using receiver operating characteristics with an AUC at 0.67 (0.57-0.78, p = .004). This ability was significantly superior to H48 AUC creatine kinase (p = .03). CONCLUSIONS: In STEMI patients, high sVCAM-1 levels are associated with a poor clinical outcome. sVCAM-1 is an early postmyocardial infarction biomarker and might be an interesting target for the development of future therapeutic strategies.