Long-term impact of postconditioning on infarct size and left ventricular ejection fraction in patients with ST-elevation myocardial infarction

Background: Ischemic postconditioning (PostC), reperfusion in brief cycles, is known to induce short-term reduction in infarct size in patients with ST elevation myocardial infarction (STEMI), especially among those with large myocardium at risk (MaR). The aim of the present study was to investigate the long-term effect of PostC on infarct size and left ventricular ejection fraction (LVEF). Methods: Sixty-eight patients with a first STEMI were randomised to primary percutaneous coronary intervention (PCI) (n = 35) or PCI followed by PostC (n = 33). MaR was determined as abnormally contracting segments on left ventricular angiogram. Cardiac magnetic resonance was performed at 3 and 12 months for the determination of infarct size and LVEF. Results: Overall there was no difference in infarct size expressed in percentage of MaR between patients randomised to the control (31%; 23, 41) and PostC (31%; 23, 43) groups at 12 months. Likewise there was no difference in LVEF between control (49%; 41, 55) and PostC (52%; 45, 55). In contrast, patients in the PostC group with MaR in the upper quartile had a significantly smaller infarct size (29%; 18, 38) than those in the control group (40%; 34, 48; p < 0.05) at 12 months. In these patients LVEF was higher in the PostC (47%; 43, 50) compared to the control group (38%; 34, 42; p < 0.01). Conclusions: In this long-term follow-up study PostC did not reduce infarct size in relation to MaR or improved LVEF in the overall study population. However, the present data suggest that PostC exerts long-term beneficial effects in patients with large MaR thereby extending previously published short-term observations

Assessment of myocardium at risk with contrast enhanced steady-state free precession cine cardiovascular magnetic resonance compared to single-photon emission computed tomography

<p>Abstract</p> <p>Background</p> <p>Final infarct size following coronary occlusion is determined by the duration of ischemia, the size of myocardium at risk (MaR) and reperfusion injury. The reference method for determining MaR, single-photon emission computed tomography (SPECT) before reperfusion, is impractical in an acute setting. The aim of the present study was to evaluate whether MaR can be determined from the contrast enhanced myocardium using steady-state free precession (SSFP) cine cardiovascular magnetic resonance (CMR) performed one week after the acute event in ST-elevation myocardial infarction (STEMI) patients with total coronary occlusion.</p> <p>Results</p> <p>Sixteen patients with STEMI (age 64 ± 8 years) received intravenous 99 m-Tc immediately before primary percutaneous coronary intervention. SPECT was performed within four hours. MaR was defined as the non-perfused myocardial volume derived with SPECT. CMR was performed 7.8 ± 1.2 days after the myocardial infarction using a protocol in which the contrast agent was administered before acquisition of short-axis SSFP cines. MaR was evaluated as the contrast enhanced myocardial volume in the cines by two blinded observers. MaR determined from the enhanced region on cine CMR correlated significantly with that derived with SPECT (r²= 0.78, p < 0.001). The difference in MaR determined by CMR and SPECT was 0.5 ± 5.1% (mean ± SD). The interobserver variability of contrast enhanced cine SSFP measurements was 1.6 ± 3.7% (mean ± SD) of the left ventricle wall volume.</p> <p>Conclusions</p> <p>Contrast enhanced SSFP cine CMR performed one week after acute infarction accurately depicts MaR prior to reperfusion in STEMI patients with total occlusion undergoing primary PCI. This suggests that a single CMR examination might be performed for determination of MaR and infarct size.</p

The role of C-reactive protein in percutaneous coronary intervention

An elevated preprocedural plasma or serum C-reactive protein (CRP) level in patients undergoing percutanous coronary intervention (PCI) is associated with short-, intermediate- and long-term outcome. Furthermore, the procedure itself has been shown to provoke an inflammatory reaction as shown by increased plasma CRP levels after PCI. The research programme resulting in this thesis focus on the role of CRP and inflammation in patients undergoing PCI. In study I 400 consecutive patients with serum levels of troponin T = 0.03 µg/l presenting with stable or unstable angina pectoris were investigated. Twenty-one percent of the patients experienced a myocardial infarction during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg/l. No difference was seen in CRP levels before PCI between patients without or with myocardial infarction during PCI. Multivariate analysis identified stent implantation, procedure time and complications during the procedure as independent predictors of myocardial infarction during PCI. In study II 121 patients with stable angina pectoris were enrolled. 100 patients were treated with a thrombin-based (Duett sealing) femoral artery closure device and 121 patients were treated with the FemoStop device. Irrespective of femoral artery closure device serum CRP and serum amyloid A (SAA) levels increased significantly after PCI. The increase was more pronounced in the Duett sealing device group compared with the FemoStop device group. In study III 100 patients with stable angina pectoris scheduled for elective PCI were prospectively enrolled. Antibodies against different pathogens were examined. Plasma CRP and IL-6 levels were measured before and 6, 24, 48, 72 hours after PCI. Neither infection with single or multiple pathogens nor a minor troponin T elevation after PCI was associated with plasma CRP or interleukin-6 (IL-6) area under the curves (AUCs). Patients treated with stent implantation had higher plasma CRP and IL-6 AUCs compared with patients treated with balloon angioplasty alone Study IV 891 consecutive patients presenting with stable or unstable angina pectoris undergoing a variety of PCIs were investigated. Serum concentrations of CRP and troponin T were determined before and the day after PCI. The mean follow-up time after PCI was 2.6 years. In multivariate analysis, patients in the highest tertile of CRP, induced by PCI, had an increased risk (risk ratio (RR) 2.48 [95% confidence interval (CI) 1.42-4.33]) for death or non-fatal myocardial infarction. Furthermore, patients in the second (RR 1.75 [95% CI 1.14-2.75]) and third (RR 2.15 [95% CI 1.37-3.36]) tertiles of the CRP response had an increased risk for coronary revascularization. Patients with periprocedural myocardial infarction with a postprocedural troponin T > 0.14 µg/l had an increased risk for death or non-fatal myocardial infarction (RR 2.65 [95% CI 1.02-6.83]). Conclusion: Periprocedural factors, whereas not the preprocedural CRP were associated with the risk of myocardial infarction during PCI. However, an elevated serum CRP concentration in response to PCI is a strong independent predictor of death or non-fatal myocardial infarction and coronary revascularization independent on myocardial injury during the procedure. Factors related to the procedure are influenced the CRP response to PCI. The results emphasize the role of CRP in coronary artery disease (CAD), and the need to develop treatments that block the increase in CRP in CAD

Effects of Myocardial Postconditioning on the Recruitment of Endothelial Progenitor Cells.

Background: Ischemic postconditioning (PostC), brief repetitive cycles of ischemia and reperfusion during early reperfusion, is suggested to protect the myocardium in patients with stent thrombosis-elevation myocardial infarction (STEMI) by improved endothelial dysfunction and alteration of cytokine release. These mechanisms are also of importance for the recruitment of endothelial progenitor cells (EPC), an endogenous repair mechanism for re-endothelialization and neoangiogenesis. The aim of this study was to investigate the effect of PostC on recruitment of EPC. Methods: EPC were analyzed in 20 patients with STEMI randomized to receive four cycles of PostC following percutaneous coronary intervention (PCI) or conventional PCI. Different subpopulations of EPC were quantified immediately and on day 4 using flow cytometry. Myocardium at risk, and infarct size was determined by cardiovascular magnetic resonance. Results: There was no influence of PostC on the number of different EPC (CD34(+) , CD133(+) , CD34(+) CD133(+) , CD34(+) KDR(+) , CD34(-) CD133(+) KDR(+) , CD34(+) CD133(+) KDR(+) ). Left ventricular ejection fraction, myocardium at risk, and infarct size did not correlate to the mobilization of EPC. There was an inverse correlation between the symptom-to-balloon time and the mobilization of progenitor precursor cells (CD34(+) cells: R =-0.527, P = 0.02; CD133(+) cells: R =-0.624, P = 0.004; CD34(+) CD133(+) cells: R =-0.466, P = 0.04). Discussion: Ischemic PostC did not result in improved mobilization of EPC in STEMI patients. The recruitment of progenitor cells seems to be related to the duration of ischemia rather than the size of the ischemic myocardial area. More effort is needed to understand the changes of endothelial surface markers by PostC and their role in EPC recruitment and homing. (J Interven Cardiol 2012;**1-8)

Effect of stent inflation pressure and post-dilatation on the outcome of coronary artery intervention : A report of more than 90 000 stent implantations

BACKGROUND: Percutaneous coronary intervention (PCI) stent inflation pressure correlates to angiographic lumen improvement and stent expansion but the relation to outcome is not clarified. Using comprehensive registry data our aim was to evaluate how stent inflation pressure influences restenosis, stent thrombosis and death following PCI. METHODS: We evaluated all consecutive coronary stent implantations in Sweden during 46 months from 2008 using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We used logistic regression and Cox proportional hazard modeling to estimate risk of outcomes with different balloon pressures. RESULTS: In total, 93 697 stents were eligible for analysis and divided into five different pressure interval groups: ≤15 atm, 16-17 atm, 18-19 atm, 20-21 atm and ≥22 atm. The risks of stent thrombosis and restenosis were significantly higher in the ≤15 atm, 18-19 atm and ≥22 atm groups (but not in the 16-17 atm group) compared to the 20-21 atm group. There were no differences in mortality. Post-dilatation was associated with a higher restenosis risk ratio (RR) of 1.22 (95% confidence interval (CI) 1.14-1.32, P&lt;0.001) but stent thrombosis did not differ statistically between procedures with or without post-dilatation. The risk of death was lower following post-dilatation (RR 0.81 (CI 0.71-0.93) P = 0.003) and the difference compared to no post-dilatation was seen immediately after PCI. CONCLUSION: Our retrospective study of stent inflation pressure identified a possible biological pattern--the risks of stent thrombosis and of restenosis appeared to be higher with low and very high pressures. Post-dilatation might increase restenosis risk

Circulating endothelial and platelet derived microparticles reflect the size of myocardium at risk in patients with ST-elevation myocardial infarction

Objectives: Microparticles (MP) are small membrane vesicles, released from activated, damaged and apoptotic endothelial cells (EMP) or platelets (PMP) that may actively modulate inflammation, coagulation and vascular function. We tested the hypothesis that the number of circulating EMP or PMP in acute myocardial infarction correlates with the myocardium at risk (MaR) and infarct size (IS). Methods: EMP were quantified in plasma samples of 36 patients (age: 63 +/- 10 years) with first time ST-elevation myocardial infarction (STEMI) using flow cytometry. EMP were defined as CD31(+)/CD42(-) MP and CD144(+) MP and PMP as CD31(+)/CD42(+) MP. MaR and IS was determined by cardiovascular magnetic resonance imaging one week after the index event. Results: Plasma levels of CD31(+)/CD42(-) EMP were 251.0 +/- 178.8/mu l and CD144(+) 106.3 +/- 33.7/mu l. PMP levels were 579.2 +/- 631.8/mu l. MaR was 31.0 +/- 11.2% of the left ventricle and IS was 11.4 +/- 7.1% of the left ventricle. Patients with STEMI in the left anterior descending artery had higher levels of CD31(+)/CD42(-) EMP and PMP than those with other infarct-related arteries (p<0.05). The numbers of CD31(+)/CD42(-) EMP and PMP correlated to MaR, but not to IS. Conclusions: Circulating EMP and PMP correlate to the size of MaR in patients with STEMI suggesting that they reflect the severity of the endothelial injury and platelet activation during myocardial ischemia. (C) 2011 Elsevier Ireland Ltd. All rights reserved

The risk of restenosis at 1 year after PCI in relation to stent inflation pressure (panel A).

<p>Estimated cumulative event rates of restenosis in relation to stent inflation pressure (panel B).</p

The risk of death at 1 year after PCI in relation to stent inflation pressure (panel A).

<p>Estimated cumulative event rates of death in relation to stent inflation pressure (panel B).</p

Estimated cumulative event rates of stent thrombosis in relation to post-dilatation (panel A).

<p>The RR of stent thrombosis of 1.18 (CI 0.95–1.32) did not differ statistically between procedures with or without post-dilatation (P = 0.19). Estimated cumulative event rates of restenosis in relation to post-dilatation (panel B). Restenosis occurred more often following post-dilatation compared with procedures where this adjunct was not used (RR 1.22 (CI 1.14–1.32) P<0.001). Estimated cumulative event rates of death in relation to post-dilatation (Panel C). The risk of death was lower following post-dilatation (RR 0.81 (CI 0.71–0.93) P = 0.003). The numbers at risk are for stent thrombosis and restenosis are identical to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056348#pone-0056348-g001" target="_blank">Figure 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056348#pone-0056348-g002" target="_blank">2</a> while the numbers at risk for death are identical to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056348#pone-0056348-g003" target="_blank">Figure 3</a>.</p