Search

Despite the fact that numerous clinical trials investigating infarct size have been completed over the last two to three decades, the methods for treating lethal reperfusion injury efficiently have only become established very recently. After several years of accumulating evidence in experimental preparations that lethal reperfusion injury might exist, the description of the phenomenon of ischaemic post-conditioning in animal models has fully convinced us of the existence and importance of irreversible myocardial damage occuring after reflow. Transfer to the clinics was possible in small phase II trials, provided care was taken to assess the determinants of infarct size and, most importantly, to consider the timing of drug administration with respect to the time of reflow. Technical questions remain to be resolved regarding the assessment of the area at risk in the difficult setting of emergency care for reperfusion therapy. Nevertheless, convincing pharmacological trials are being performed that mark the start of a new era that will, in the future, improve the prognosis of patients with ST-segment elevation myocardial infarction through the prevention of lethal myocardial reperfusion injury. At present, while erythropoietin and adenosine have not proved efficient for alleviation of lethal reperfusion injury, a significant benefit has been reported for cyclosporin and exenatide. New pharmacological agents need to be identified and tested in phase II trials. In the meantime, clinical outcome studies are currently being conducted for cyclosporin. [ABSTRACT FROM PUBLISHER]

Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6‐thioguanine nucleotides (6‐TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as follows: (a) to carry out a phenotypic study of RBC IMPDH activity in adults and children treated or not with azathioprine (AZA) for autoimmune diseases, and (b) to investigate the relationship between the activities of IMPDH, thiopurine metabolites, inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT). IMPDH activity was determined in 97 adults and 67 children treated or not with AZA. 6‐Thioguanine nucleotides (6‐TGN), 6‐methylmercaptopurine nucleotide (6‐MeMPN) levels, and ITPA as well as TPMT activities were measured in RBCs by HPLC. Using the Gaussian mixture model, distribution of IMPDH activity was evaluated. Influence of age, sex and AZA treatment on IMPDH activity was also assessed. A bimodal distribution in IMPDH activity was found with 87% of patients exhibiting normal activity and 13% of patients with high activity. No influence of age, sex and AZA therapy was found. There is no relationship between TPMT, ITPA and IMPDH activities. A negative correlation between IMPDH activity and 6‐MeMPN was shown in adults and children (rs = −0.335 P = 0.014 and rs = −0.383 P = 0.012, respectively). Our results suggest that AZA‐treated patients exhibiting lower IMPDH activity could have higher Me‐6MPN levels with higher risk of hepatotoxicity. We demonstrated that RBC matrix could be an interesting alternative to lymphocyte matrix to monitor thiopurine metabolites and enzyme activity. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates.Objectives: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD.Methods: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year.Results: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02).Conclusions: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555). [ABSTRACT FROM AUTHOR]

Aims: Periprocedural myocardial infarctions have been reported in the setting of planned percutaneous coronary intervention (PCI). We assessed the prevalence of nonculprit artery acute myocardial infarction (NCAMI) and its relationship with coronary artery characteristics, final infarct size, and 1-year adverse clinical outcomes in a population of anterior ST-elevated myocardial infarction (STEMI) patients. Methods and Results: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) studies were performed within 7 days of admission in 129 anterior STEMI patients from the CIRCUS trial treated by primary PCI. Infarct in the noninfarct artery territory (circumflex, right coronary) was assessed on LGE-CMR and T2-weighted images. Eleven (8.5%) patients exhibited NCAMI. The only independent characteristic significantly associated with NCAMI was the presence of multiple complex coronary lesions (odds ratio = 12.9, 95% confidence interval [3.1–53.4]; p < 0.001). There was a significantly increased infarct size in NCAMI patients compared to patients without NCAMI (45.8 ± 20.4% of the left ventricle [LV] vs. 31.0 ± 15.1% of LV, respectively; p = 0.02), with lower LV ejection fraction (46 ± 10% vs. 34 ± 8%, respectively; p < 0.001). Conclusion: NCAMIs are present in 8.5% of anterior STEMI patients and are significantly associated with multiple complex coronary lesions without significant relationship to any revascularization procedural technique. NCAMI was associated with a greater infarct size and reduced LVEF but not worse clinical outcomes at 1 year. [ABSTRACT FROM AUTHOR]