Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling.

BACKGROUND: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. AIMS: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). METHODS: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. RESULTS: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). CONCLUSION: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Usefulness of early rule-in and rule-out biomarker protocols to estimate ischemia-induced myocardial injury in early chest pain presenters.

Protocols to minimize the time between 2 measurements of troponin or a combination with copeptin have been developed to rapidly rule-in or rule-out myocardial injury (MI) in patients with chest pain. These fast track protocols to rule-in and rule-out MI are not sufficiently validated for early chest pain presenters. The "early presenter" model was tested in 107 stable patients after a short period of myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI), and copeptin were measured at the start and 90, 180, and 360 minutes after stent implantation. MI was defined as a troponin level more than the upper limit of normal (ULN) and an absolute increase of >50% ULN on the 360-minute sample. A single combined measurement of troponin and copeptin 90 minutes after the onset of ischemia has a low diagnostic value. This increases when serial measurements with 90-minute intervals are included. For ruling in MI, the highest positive predictive value (with a 95% confidence interval [CI]) can be obtained when focusing only on the increase in troponin level, with a positive predictive value of 86% (70, 93) and 80% (67, 90) for hsTnT and hsTnI, respectively. For ruling out MI, a combined absence of any troponin more than the ULN and any significant increase in troponin level perform best with a negative predictive value of 75% (55, 89) and 75% (55, 89) for hsTnT and hsTnI, respectively. In conclusion, in early presenters, rapid biomarker protocols underestimate MI. A standard biomarker assessment after 3 hours is required to adequately rule-in or rule-out myonecrosis.

Levels of circulating CD34+/KDR+ cells do not predict coronary in-stent restenosis.

BACKGROUND: Angiographic and clinical parameters are poor predictors of in-stent restenosis. Bone marrow-derived CD34(+) cells that coexpress a receptor for vascular endothelial growth factor (kinase insert domain receptor [KDR]) are committed to endothelial lineage. Mobilization and infusion of CD34(+)/KDR(+) cells accelerates re-endothelialization and reduces neointimal thickness in vascular injury models. Bioengineered stents capturing CD34(+) cells also show expedited re-endothelialization. We examined whether circulating CD34(+)/KDR(+) cell counts can be used to predict restenosis in a bare-metal stent (BMS). METHODS: CD34(+)/KDR(+) cells were counted by flow cytometry in 124 nondiabetic patients before BMS implantation and the relation to in-stent late luminal loss (LLL) was examined by angiography at 6 months (primary end point). Neointima was also quantified as the maximum percentage area stenosis (M%AS) and percentage volume intima hyperplasia (%VIH) on intravascular ultrasonography (secondary end points). RESULTS: Multiple linear regression analysis, taking into account implanted stent length and diameter, revealed no relation between CD34(+)/KDR(+) cell counts and LLL (partial regression coefficient b = 0.11; 95% confidence interval [CI], -0.19-0.42; P = 0.46). Similarly, no relation between CD34(+)/KDR(+) cell counts and M%AS or %VIH could be demonstrated. Moreover, the increase in CD34(+)/KDR(+) cell counts over 6 months was unrelated to LLL (b = -0.15; 95% CI, -0.42-0.12; P = 0.28), M%AS, and %VIH. CONCLUSIONS: Although our study does not exclude a pathophysiologic role for CD34(+)/KDR(+) cells in the formation of neointima, cell counts before percutaneous coronary intervention proved to be unrelated to LLL or intravascular ultrasonographically derived restenosis parameters in coronary BMSs at 6 months.

Difference in clinical target lesion revascularization between a silicon carbide-coated and an uncoated thin strut bare-metal stent: the PRO-Vision study.

BACKGROUND: Bare-metal stents trigger a foreign body reaction, resulting in neointima formation and restenosis. Silicon carbide (SiC) coating shields the metal from circulating blood and vessel wall, both potential sources of neointima smooth muscle cells. METHODS: We investigated whether SiC-coated stents (PRO-Kinetic) have lower clinical target lesion revascularization (TLR) rates than do uncoated bare-metal stents (Vision). Stents were implanted in 2731 patients during 2 consecutive 18-month periods. Clinical TLR was evaluated at 1 year. RESULTS: In the PRO-Kinetic group, TLR was significantly higher (9.0% vs 5.6%; unadjusted odds ratio, 1.61; 95% confidence interval [CI], 1.24-2.08; P < 0.001) compared with the Vision group. After adjustment for postintervention minimal luminal diameter (adjusted odds ratio [AOR], 0.56; 95% CI, 0.42-0.73), total implanted stent length (AOR, 1.01; 95% CI, 1.00-1.02), non-ST-segment elevation myocardial infarction or unstable angina at initial presentation (AOR, 1.89; 95% CI, 1.41-2.54), and triple vessel stenting (AOR, 2.68; 95% CI, 1.02-7.05), the use of PRO-Kinetic stents remained an independent predictor for revascularization (AOR, 1.57; 95% CI, 1.18-2.10; P = 0.002). Because strut thickness is lower in 2.0- to 3.0-mm PRO-Kinetic stents, a subgroup analysis (n = 2382 lesions) was performed. Even in this subgroup, PRO-Kinetic implantation proved an independent predictor of TLR (AOR, 1.62; 95% CI, 1.17-2.23; P = 0.003). CONCLUSION: In contrast to theoretical expectations, the SiC-coated PRO-Kinetic stent was associated with greater target lesion revascularization rates at 1 year compared with the uncoated Vision stent.