scholarly journals Acute myocardial infarction in young adults: features of pathogenesis, disease course and justification of strategy for prevention of complications

2019 ◽  
Vol 26 (4) ◽  
pp. 32-43
Author(s):  
O. M. Parkhomenko ◽  
Ya. M. Lutay ◽  
O. I. Irkin ◽  
D. O. Bilyi ◽  
A. O. Stepura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Young Adults ◽  
Young Patients ◽  
Coronary Vessels ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Premature Coronary Artery Disease ◽  
Ventricular Ejection Fraction ◽  
Arrhythmogenic Substrate

We retrospectively and prospectively studied 835 patients with acute myocardial infarction (AMI) under the age of 45 and older. Depending on age, patients were divided into two groups: < 45 years and ≥ 45 years. In 189 patients under 45 years of age, the main risk factors leading to the development of ST-elevation myocardial infarction were male sex (OR 6.58; 95 % CI (2.64–16.41), smoking (OR 2.02; 95 % CI (1.44–2.82) and family history of premature coronary artery disease (OR 1.75; 95 % CI (1.21–2.54). According to coronary angiography, AMI patients under 45 years of age in most cases showed no hemodynamically significant coronary vessels damage and had a different course of AMI caused by other reasons – aneurysms of the coronary arteries, muscle bridges, coronary spasm, spontaneous dissections. It was found that 10 % of young patients who did not have obstructive lesions of coronary vessels, according to magnetic resonance imaging (MRI) had focal myocarditis. However, it is noted that in patients under 45 years of age, the presence of familial hypercholesterolemia (FH) may affect the development of AMI. Thus, according to the DLCNS criteria, FH was more frequently reported in young patients than in patients older than 45 years (7.34 % vs 1.32 % (p<0.05)). Hospital course of AMI in young adults was more favorable, with fewer complications. Data from studies of flow-dependent vasodilation have shown that young patients have worse endothelial function on the 1st day of AMI (p=0.043), but better recovery of it in the dynamics of observation. However, in young patients, early (day 7, p=0.029) and late (day 90, p=0.041) left ventricular dilatation was more commonly reported compared with older patients. According to the MRI data on day 1 and in the dynamics (90 days), it was found that, despite the higher prevalence of AMI, young patients have better recovery of contractile myocardial function. The arrhythmogenic substrate (according to late ventricular potential) for life-threatening arrhythmias was more commonly recorded in the older age group at the beginning of the development of AMI, but it was detected with the same frequency in both groups during prolonged observation (6–12 months). Despite better survival and fewer complications during long-term follow-up (4.9 years on average), the greatest impact on the development of the combined endpoint (cardiovascular death / recurrent myocardial infarction / stroke) and death from any cause was made by the patients’ age up to 35 years (best prognosis), concomitant hypertension (worsens prognosis) and low left ventricular ejection fraction (increases complications). The study indicates the possibility of implementing a secondary prevention system in AMI patients of young age through careful (active) observation and control of adherence to treatment and the adequacy of its implementation.

scholarly journals PIK3R1, SPNB2, and CRYAB as Potential Biomarkers for Patients with Diabetes and Developing Acute Myocardial Infarction

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yue Zheng ◽  
Yuheng Lang ◽  
Zhenchang Qi ◽  
Wenqing Gao ◽  
Xiaomin Hu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Young Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Venn Diagram ◽  
Hub Genes ◽  
Ventricular Ejection Fraction ◽  
Pathway Analyses ◽  
Potential Biomarkers

Background. Young patients with type 2 diabetes mellitus (DM) and acute myocardial infarction (AMI) have high long-term all-cause and cardiovascular mortality rates. We aimed to investigate the differentially expressed genes (DEGs) that might be potential targets for DM patients with AMI. Methods. Gene datasets GSE775, GSE19322, and GSE97494 were meta-analyzed to obtain DEGs of the left ventricle myocardium in infarcted mice. Gene datasets including GSE3313, GSE10617, and GSE136948 were meta-analyzed to identify DEGs in diabetes mice. A Venn diagram was used to obtain the overlapping DEGs. KEGG and GO pathway analyses were performed, and hub genes were obtained. Pivotal miRNAs were predicted and validated using the miRNA dataset in GSE114695. To investigate the cardiac function of the screened genes, a MI mouse model was constructed; echocardiogram, qPCR, and ELISA of hub genes were performed; ELISA of hub genes in human blood samples was also utilized. Results. A total of 67 DEGs were identified, which may be potential biomarkers for patients with DM and AMI. GO and KEGG pathway analyses were performed, which were mainly enriched in response to organic cyclic compound and PI3K-Akt signaling pathway. The expression of PIK3R1 and SPNB2 increased in the MI group and was negatively correlated to left ventricular ejection fraction (LVEF), whereas that of CRYAB decreased and was positively correlated to LVEF. Patients with high CRYAB expression demonstrated a short hospital stay and the area under the curves of the three protein levels before and after treatment were 0.964, 0.982, and 0.918, suggesting that PIK3R1, SPNB2, and CRYAB may be diagnostic and prognostic biomarkers for the diabetes patients with AMI. Conclusion. The screened hub genes, PIK3R1, SPNB2, and CRYAB, were validated as credible molecular biomarkers and may provide a novel therapy for diabetic cardiac diseases with increased proteotoxic stress.

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF &lt;45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect &gt;3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

Abstract 12691: Long-term Optimal Medical Therapy for Patients With Mid-range Left Ventricular Ejection Fraction After Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
YeeKyoung KO ◽  
Seungjae JOO ◽  
Jong Wook Beom ◽  
Jae-Geun Lee ◽  
Joon-Hyouk CHOI ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Medical Therapy ◽  
Beta Blockers ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Ras Inhibitors

Introduction: In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (40% <EF<50%) becomes increasing. However, the long-term optimal medical therapy for these patients has been rarely studied. Aims: This observational study aimed to investigate the association between the medical therapy with beta-blockers or inhibitors of renin-angiotensin system (RAS) and clinical outcomes in patients with mid-range EF after AMI. Methods: Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results: Patients with beta-blockers showed significantly lower 1-year cardiac death (2.4 vs. 5.2/100 patient-year; hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.22-0.98; P =0.045) and MI (1.7 vs. 4.0/100 patient-year; HR 0.41; 95% CI 0.18-0.95; P =0.037). On the other hand, RAS inhibitors were associated with lower 1-year re-hospitalization due to heart failure (2.8 vs. 5.5/100 patient-year; HR 0.54; 95% CI 0.31-0.92; P =0.024), and no significant interaction with classes of RAS inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) was observed ( P for interaction=0.332). Conclusions: Beta-blockers or RAS inhibitors at discharge were associated with better 1-year clinical outcomes in patients with mid-range EF after AMI.

scholarly journals Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease

2020 ◽  
Vol 21 (13) ◽  
pp. 4591
Author(s):  
Denise Traxler ◽  
Andreas Spannbauer ◽  
Patrick Einzinger ◽  
Julia Mester-Tonczar ◽  
Dominika Lukovic ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Late Enhancement ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Systolic Volume ◽  
End Diastolic Volume

Clusterin exerts anti-inflammatory, cytoprotective and anti-apoptotic effects. Both an increase and decrease of clusterin in acute myocardial infarction (AMI) has been reported. We aimed to clarify the role of clusterin as a systemic biomarker in AMI. AMI was induced by percutaneous left anterior artery (LAD) occlusion for 90 min followed by reperfusion in 24 pigs. Contrast ventriculography was performed after reperfusion to assess left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) and additional cMRI + late enhancement to measure infarct size and LV functions at day 3 and week 6 post-MI. Blood samples were collected at prespecified timepoints. Plasma clusterin and other biomarkers (cTnT, NT-proBNP, neprilysin, NGAL, ET-1, osteopontin, miR21, miR29) were measured by ELISA and qPCR. Gene expression profiles of infarcted and remote region 3 h (n = 5) and 3 days (n = 5) after AMI onset were analysed by RNA-sequencing. AMI led to an increase in LVEDV and LVESV during 6-week, with concomitant elevation of NT-proBNP 3-weeks after AMI. Plasma clusterin levels were increased immediately after AMI and returned to normal levels until 3-weeks. Plasma NGAL, ET-1 and miR29 was significantly elevated at 3 weeks follow-up, miR21 increased after reperfusion and at 3 weeks post-AMI, while circulating neprilysin levels did not change. Elevated plasma clusterin levels 120 min after AMI onset suggest that clusterin might be an additional early biomarker of myocardial ischemia.

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