No benefit of sacubitril–valsartan after acute MI

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity. Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay. Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05). Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.

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Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey

Lipids in Health and Disease ◽

10.1186/s12944-021-01467-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Hermann Yao ◽

Michel Farnier ◽

Laura Tribouillard ◽

Frédéric Chague ◽

Philippe Brunel ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Ldl Cholesterol ◽

Statin Treatment ◽

Lipid Lowering ◽

Syntax Score ◽

Lipid Lowering Therapy ◽

Lipid Clinic ◽

Acute Mi ◽

Artery Disease

Abstract Background Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. Methods The data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2). Results Although LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001). Conclusions FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

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A Woman with Shock and Normal Cardiac Output After Acute MI

Hospital Practice ◽

10.1080/21548331.1993.11442857 ◽

1993 ◽

Vol 28 (sup6) ◽

pp. 90-92

Author(s):

John Frierson ◽

William Stiles ◽

Donald McKillop ◽

Robert Bain

Keyword(s):

Cardiac Output ◽

Acute Mi

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Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22031390 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1390

Author(s):

Julia Mester-Tonczar ◽

Patrick Einzinger ◽

Johannes Winkler ◽

Nina Kastner ◽

Andreas Spannbauer ◽

...

Keyword(s):

Myocardial Infarction ◽

Progenitor Cells ◽

Regulatory Networks ◽

Circular Rnas ◽

Cardiac Progenitor Cells ◽

Tissue Samples ◽

Healthy Myocardium ◽

Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

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Managed care improves prognosis in acute myocardial infarction survivors. Data from the MAnaged Care for Acute Myocardial Infarction Survivors (MACAMIS) Programme

European Heart Journal ◽

10.1093/ehjci/ehaa946.1309 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Jankowski ◽

R Topor-Madry ◽

M Gasior ◽

U Ceglowska ◽

Z Eysymontt ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Multivariate Analysis ◽

Managed Care ◽

Care Programme ◽

Wide System ◽

Care Assessment ◽

Acute Mi ◽

One Year ◽

Overall Mortality

Abstract Background Mortality following acute myocardial infarction (MI) remains high despite progress in pharmacotherapy and interventional treatment. In 2017 a nation-wide system of managed care for MI survivors comprising a continuum of acute treatment of MI, staged revascularization, cardiac rehabilitation, cardiac electrotherapy and cardiac ambulatory care within one year following MI was implemented in Poland. The managed care programme (MCP) includes also the quality of care assessment based on clinical measures (e.g. cardiovascular risk factors control) as well as on the rate of minor and major cardiovascular events. The goal of the analysis was to assess the overall mortality of MI survivors participating and not participating in the MCP. Methods The database of survivors of acute MI discharged from hospital from October 1, 2017 to December 31, 2018 was analyzed. Patients who died within 10 days after discharge were excluded from the analysis. The primary end-point was defined as death from any cause. Propensity-Score Matching (PSM) using nearest neighbor matching was used to form comparable groups of patients participating and not participating in the MCP. The Cox proportional hazard regression analysis was used to assess the relation between MCP and the overall mortality. Results MCP was implemented in the first stage in 48 hospitals spread around the country (about 34% of all hospitals treating acute MI patients in Poland). Out of 87739 analyzed patients (age: 68.1±11.9 years; 55581 men and 32158 women) 34064 were hospitalized in hospitals with MCP implemented. Altogether 10404 patients (11.9% of the whole cohort; 30.5% of those hospitalized in hospitals with MCP implemented) participated in MCP. They were matched with 10404 patients not participating in the MCP. During 324.8±140.5 days of follow-up 7413 patients died. One-year mortality was lower in patients participating in the MCP both when we analyzed the whole cohort (4.4% vs. 9.5%; p<0.001) as well as when we limited the analysis to the PSM groups (4.4% vs. 6.5%; p<0.001, figure 1). MCP was related to the overall mortality in univariate (HR 0.43 [0.39–0.48]) as well as in multivariate analysis (0.64 [0.57–0.71]) in the whole cohort as well as in the PSM cohort (HR 0.63 [0.56–0.72] and 0.64 [0.56–0.72] for the univariate and multivariate analysis respectively). When we limited the analysis to hospitals in which MCP was implemented one-year mortality was 4.3% vs. 6.3% (p<0.001) whereas univariate HR was 0.51 (0.44–0.60) and multivariate HR 0.52 (0.44–0.61). Conclusion The implemented in Poland nation-wide system of managed care for MI survivors is related to improved survival. Therefore, the Ministry of Health plans to implement the programme in all cardiac centers in Poland. Funding Acknowledgement Type of funding source: None

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