Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

The Occluded Artery Trial (OAT) Viability Ancillary Study (OAT-NUC): influence of infarct zone viability on left ventricular remodeling after percutaneous coronary intervention versus optimal medical therapy alone.

BACKGROUND: The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) versus optimal medical therapy (MED) in patients with persistent total occlusion of the infarct-related artery 3 to 28 days post-myocardial infarction. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ) viability is unknown. METHODS AND RESULTS: The OAT nuclear ancillary study hypothesized that (1) IZ viability influences left ventricular (LV) remodeling and that (2) PCI as compared with MED attenuates adverse remodeling in post-myocardial infarction patients with preserved viability. Enrolled were 124 OAT patients who underwent resting nitroglycerin-enhanced technetium-99m sestamibi single-photon emission computed tomography (SPECT) before OAT randomization, with repeat imaging at 1 year. All images were quantitatively analyzed for infarct size, IZ viability, LV volumes, and function in a core laboratory. At baseline, mean infarct size was 26% ± 18 of the LV, mean IZ viability was 43% ± 8 of peak uptake, and most patients (70%) had at least moderately retained IZ viability. There were no significant differences in 1-year end-diastolic or end-systolic volume change between those with severely reduced versus moderately retained IZ viability, or when compared by treatment assignment PCI versus MED. In multivariable models, increasing baseline viability independently predicted improvement in ejection fraction (P = .005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling. CONCLUSIONS: In the contemporary era of MED, PCI of the infarct-related artery compared with MED alone does not impact LV remodeling irrespective of IZ viability.

Impact of left ventricular ejection fraction on clinical outcomes over five years after infarct-related coronary artery recanalization (from the Occluded Artery Trial [OAT]).

In the Occluded Artery Trial (OAT), percutaneous coronary intervention (PCI) of an infarct-related artery on days 3 to 28 after acute myocardial infarction was of no benefit compared to medical therapy alone. The present analysis was conducted to determine whether PCI might provide benefit to the subgroup of higher risk patients with a depressed ejection fraction (EF). Of 2,185 analyzed patients (age 58.6 +/- 11.0 years) with infarct-related artery occlusion on days 3 to 28 after acute myocardial infarction in the Occluded Artery Trial, 1,094 were assigned to PCI and 1,091 to medical therapy. The primary end point was a composite of death, reinfarction, and New York Heart Association class IV heart failure. The outcomes were analyzed by EF (first tertile, EF < or =44%, vs second and third tertiles combined, EF >44%). Interaction of the treatment effect with EF on the study outcomes were examined using the Cox survival model. The 5-year rates of the primary end point (death, reinfarction, or New York Heart Association class IV heart failure) were not different in either subgroup (PCI vs medical therapy, hazard ratio 1.25, 99% confidence interval 0.83 to 1.88, for EF < or =44%; hazard ratio 0.98, 99% confidence interval 0.64 to 1.50, for EF >44%). However, in patients with an EF >44%, PCI reduced the rate of subsequent revascularization (p = 0.004, interaction p = 0.05). In conclusion, optimal medical therapy remains the overall treatment of choice for stable patients with a persistent total occlusion of the infarct-related artery after acute myocardial infarction, irrespective of the baseline EF. In patients with normal or moderately impaired left ventricular contractility, PCI reduced the need for subsequent revascularization but did not otherwise improve outcomes.