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Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

ABSTRACT: Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12?h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20?h (interquartile range: 15-25?h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p?=?3.44?×?10-5), and regulation of inflammatory response (p?=?1.86?×?10-3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction.

SUBMITTER: Teren A

PROVIDER: S-EPMC5290530 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

Teren A A Kirsten H H Beutner F F Scholz M M Holdt L M LM Teupser D D Gutberlet M M Thiery J J Schuler G G Eitel I I

Scientific reports 20170203

Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarc ...[more]

PMID: 28155873

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Project description:BackgroundThis study aimed to evaluate the incremental prognostic value of infarct size, microvascular obstruction (MO), myocardial salvage index (MSI), and left ventricular ejection fraction (LV-EFCMR) assessed by cardiac magnetic resonance imaging (CMR) in comparison to traditional outcome markers in patients with ST-elevation myocardial infarction (STEMI) reperfused by primary percutaneous intervention (PCI).MethodsSTEMI patients reperfused by primary PCI (n=278) within 12 hours after symptom onset underwent CMR three days after the index event (interquartile range [IQR] two to four). Infarct size and MO were measured 15 minutes after gadolinium injection. T2-weighted and contrast-enhanced CMR were used to calculate MSI. In addition, traditional outcome markers such as ST-segment resolution, pre- and post-PCI Thrombolysis In Myocardial Infarction (TIMI)-flow, maximum level of creatine kinase-MB, TIMI-risk score, and left ventricular ejection fraction assessed by echocardiography were determined in all patients. Clinical follow-up was conducted after 19 months (IQR 10 to 27). The primary endpoint was defined as a composite of death, myocardial reinfarction, and congestive heart failure (MACE).ResultsIn multivariable Cox regression analysis, adjusting for all traditional outcome parameters significantly associated with the primary endpoint in univariable analysis, MSI was identified as an independent predictor for the occurrence of MACE (Hazard ratio 0.94, 95% CI 0.92 to 0.96, P<0.001). Further, C-statistics comparing a model including only traditional outcome markers to a model including CMR parameters on top of traditional outcome markers revealed an incremental prognostic value of CMR parameters (0.74 versus 0.94, P<0.001).ConclusionsCMR parameters such as infarct size, MO, MSI, and LV-EFCMR add incremental prognostic value above traditional outcome markers alone in acute reperfused STEMI.Trial registrationClinicaltrials.gov NCT00463749, Clinicaltrials.gov NCT00359918.

Project description:BACKGROUND:Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS:STEMI patients underwent 3?T cardiovascular magnetic resonance (CMR), within 3?h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3?h was compared with changes at 24-h to predict final infarct size. RESULTS:Forty patients were included in this study. Patients with average T1 values of AAR ?1400?ms within 3?h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P?=?0.003) and at 6-months (27% ±9 vs. 12% ±9; P?<?0.001), higher incidence and larger extent of MVO (85% vs. 40%, P?=?0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P?=?0.025]. The average T1 value was an independent predictor of acute LGE (? 0.61, 95%CI 0.13 to 1.09; P?=?0.015), extent of MVO (? 0.22, 95%CI 0.03 to 0.41, P?=?0.028) and final infarct size (? 0.63, 95%CI 0.21 to 1.05; P?=?0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE >?9.5%) with 100% positive predictive value at the optimal cut-off of 1400?ms (area-under-the-curve, AUC 0.88, P?=?0.006). CONCLUSION:Hyper-acute T1 values of the AAR (within 3?h post PPCI, but not 24?h) predict a larger extent of MVO and infarct size at both 24?h and 6?months follow-up. Delayed CMR scanning for 24?h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Dataset Information

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

Publications

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction.

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