Dataset Information

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction.

ABSTRACT:

Introduction

Diastolic dysfunction is an important predictor of poor outcome after myocardial infarction. Metformin treatment improved diastolic function in animal models and patients with diabetes. Whether metformin improves diastolic function in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unknown.

Methods

The GIPS-III trial randomized STEMI patients, without known diabetes, to metformin or placebo initiated directly after PCI. The previously reported primary endpoint was left ventricular ejection fraction at 4 months, which was unaffected by metformin treatment. This is a predefined substudy to determine an effect of metformin on diastolic function. For this substudy trans-thoracic echocardiography was performed during hospitalization and after 4 months. Diastolic dysfunction was defined as having the combination of a functional alteration (i.e. decreased tissue velocity: mean of septal e' and lateral e') and a structural alteration (i.e. increased left atrial volume index (LAVI)). In addition, left ventricular mass index and transmitral flow velocity (E) to mean e' ratio (E/e') were measured to determine an effect of metformin on individual echocardiographic markers of diastolic function.

Results

In 237 (63%) patients included in the GIPS-III trial diastolic function was measured during hospitalization as well as at 4 months. Diastolic dysfunction was present in 11 (9%) of patients on metformin and 11 (9%) patients on placebo treatment (P = 0.98) during hospitalization. After 4 months 22 (19%) of patients with metformin and 18 (15%) patients with placebo (P = 0.47) had diastolic dysfunction. In addition, metformin did not improve any of the individual echocardiographic markers of diastolic function.

Conclusions

In contrast to experimental and observational data, our randomized placebo controlled trial did not suggest a beneficial effect of short-term metformin treatment on diastolic function in STEMI patients.

SUBMITTER: Al Ali L

PROVIDER: S-EPMC5158040 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction.

Al Ali Lawien L Hartman Minke T MT Lexis Chris P H CP Hummel Yoran M YM Lipsic Erik E van Melle Joost P JP van Veldhuisen Dirk J DJ Voors Adriaan A AA van der Horst Iwan C C IC van der Harst Pim P

PloS one 20161215 12

<h4>Introduction</h4>Diastolic dysfunction is an important predictor of poor outcome after myocardial infarction. Metformin treatment improved diastolic function in animal models and patients with diabetes. Whether metformin improves diastolic function in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unknown.<h4>Methods</h4>The GIPS-III trial randomized STEMI patients, without known diabetes, to metformin or placebo initiated directly after PCI. The previously re ...[more]

PMID: 27977774

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Project description:Objective: ST-segment Elevation Myocardial Infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using percutaneous coronary intervention (PCI), a large percentage of myocardial cells die after reperfusion which is recognized as ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPCs) are a group of oxidized lipids generated through non-enzymatic oxidation and have pro-inflammatory properties. This study aimed to examine the roles of OxPCs in a clinical setting of myocardial I/R. Methods: Blood samples were collected from STEMI patients at presentation prior to primary PCI (PPCI) (Isch) and at 4 time-points post-PPCI, including 2 h (R-2 h), 24 h (R-24 h), 48 h (R-48 h), and 30 days (R-30 d) post-PPCI. As controls, blood samples were collected from patients with non-obstructive coronary artery disease after diagnostic coronary angiography. Aspiration thrombectomy was also performed in selected STEMI patients. High-performance lipid chromatography-electrospray mass spectrometry (LC-MS/MS) was used for OxPCs analysis. Results: Twenty-two distinct OxPC species were identified and quantified in plasma samples in patients presenting with STEMI. These compounds were categorized as fragmented and non-fragmented species. Total levels of OxPCs did not significantly differ between Isch and control groups. However, total levels of fragmented OxPCs increased significantly in the ischemic period compared with controls (Isch: 4.79 ± 0.94, Control: 1.69 ± 0.19 ng/μl of plasma, P < 0.05). Concentrations of non-fragmented OxPCs had significant reductions during ischemia compared to the control group (Isch: 4.84 ± 0.30, Control: 6.6 ± 0.51 ng/μl, P < 0.05). Levels of total OxPCs in patients with STEMI were not significantly different during reperfusion periods. However, fragmented OxPCs levels were elevated at 48 h post-reperfusion and decreased at 30 days following MI, when compared to R-2 h and R-24 h time points (Isch: 4.79 ± 0.94, R-2 h: 5.33 ± 1.17, R-24 h: 5.20 ± 1.1, R-48 h: 4.18 ± 1.07, R-30 d: 1.87 ± 0.31 ng/μl, P < 0.05). Plasma levels of two fragmented OxPCs, namely, POVPC and PONPC were significantly correlated with peak creatine kinase (CK) levels (P < 0.05). As with plasma levels, the dominant OxPC species in coronary aspirated thrombus were fragmented OxPCs, which constituted 77% of total OxPC concentrations. Conclusion: Biologically active fragmented OxPC were elevated in patients presenting with STEMI when compared to controls. PONPC concentrations were subsequently increased after PPCI resulting in reperfusion. Moreover, levels of POVPC and PONPC were also associated with peak CK levels. Since these molecules are potent stimulators for cardiomyocyte cell death, therapeutics attenuating their activities can result in a novel therapeutic pathway for myocardial salvage for patients undergoing reperfusion therapy.

Project description:Background Adenosine is used to treat no-reflow in the infarct-related artery (IRA) during ST-segment-elevation myocardial infarction intervention. However, the physiological effect of adenosine in the IRA is variable. Coronary steal-a reduction of blood flow to the distal coronary bed-can occur in response to adenosine and this is facilitated by collaterals. We investigated the effects of adenosine on coronary flow reserve (CFR) in patients presenting with ST-segment-elevation myocardial infarction to better understand the physiological mechanism underpinning the variable response to adenosine. Methods and Results Pressure-wire assessment of the IRA after percutaneous coronary intervention was performed in 93 patients presenting with ST-segment-elevation myocardial infarction to calculate index of microvascular resistance, CFR, and collateral flow index by pressure. Modified collateral Rentrop grade to the IRA was recorded, as was microvascular obstruction by cardiac magnetic resonance imaging. Coronary steal (CFR <0.9), no change in flow (CFR=0.9-1.1), and hyperemic flow (CFR >1.1) after adenosine occurred in 19 (20%), 15 (16%), and 59 (63%) patients, respectively. Patients with coronary steal had higher modified Rentrop score to the IRA (1 [0, 1.75] versus 0 [0, 1], P<0.001) and a higher collateral flow index by pressure (0.25±0.10 versus 0.15±0.10, P=0.004) than the hyperemic group. The coronary steal group also had significantly higher index of microvascular resistance (61.68 [28.13, 87.04] versus 23.93 [14.67, 37.00], P=0.006) and had more disease (stenosis >50%) in the donor arteries (52.63% versus 22.03%, P=0.02) than the hyperemic group. Conclusions Adenosine-induced coronary steal may be responsible for a reduction in coronary flow reserve in a proportion of patients presenting with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03145194. URL: https://www.isrctn.com; Unique identifier: ISRCTN3176727.

Dataset Information

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction.

Introduction

Methods

Results

Conclusions

Publications

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction.

Similar Datasets

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