Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction.

Despite prompt epicardial recanalization in patients presenting with ST-segment elevation myocardial infarction (STEMI), coronary microvascular obstruction and dysfunction (CMVO) is still fairly common and is associated with poor prognosis. Various pharmacological and mechanical strategies to treat CMVO have been proposed, but the positive results reported in preclinical and small proof-of-concept studies have not translated into benefits in large clinical trials conducted in the modern treatment setting of patients with STEMI. Therefore, the optimal management of these patients remains a topic of debate. In this Review, we appraise the pathophysiological mechanisms of CMVO, explore the evidence and provide future perspectives on strategies to be implemented to reduce the incidence of CMVO and improve prognosis in patients with STEMI.

Impact of drug-eluting balloon (pre- or post-) dilation on neointima formation in de novo lesions treated by bare-metal stent: the IN-PACT CORO trial.

UNLABELLED: The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre-DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm(2) (p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting). CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov . Identifier: NCT01057563.

Adenosine as an Adjunct Therapy in ST Elevation Myocardial Infarction Patients: Myth or Truth?

Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to attenuate ischemia reperfusion injury, and thus represents a promising therapeutic option for treating such patients. However, previous randomized clinical trials have collectively failed to demonstrate whether adenosine can effectively reduce measures of myocardial injury and improve clinical outcome, despite its good basic evidence. The failure of such trials to show a real beneficial action may be in part related to specific factors other than adenosine's clinical efficacy. The purpose of this review is to explain the rationale for the use of adenosine as an adjunctive pharmacological cardio-protective agent following reperfusion of the ischemic myocardium, to address the weakness of previous trials and to summarize the current state of knowledge regarding the effect of adenosine administration on reperfusion myocardial injury in patients with myocardial infarction. Although some preclinical and clinical studies point towards the beneficial role of adenosine in the prevention and treatment of no-reflow phenomenon in myocardial infarction, many unanswered questions still remain, including the optimal clinical indication, mode, dosage, duration and timing of application, and the exact mechanisms leading to potential benefits. Clarifying these issues will depend on further properly designed, adequately powered and well conducted clinical trials, which will probably provide us with the definite answers.

INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO): study protocol for a randomized controlled trial.

BACKGROUND: Neointimal hyperplasia plays a pivotal role in the pathogenesis of in-stent restenosis in patients undergoing percutaneous coronary interventions. Drug-eluting balloons are a promising tool to prevent restenosis after coronary angioplasty. Moreover, an increased knowledge of the pathophysiology of restenosis my help improve therapeutic strategies. METHODS/DESIGN: We present the design of an open-label, randomized three-arm clinical trial aimed to assess whether a strategy of bare-metal stent implantation with additional use of drug-eluting balloons, either before (pre-dilation) or after stenting (post-dilation), reduces the primary endpoint of in-stent neointimal hyperplasia area as compared with a strategy of bare-metal stent implantation alone. This primary endpoint will be assessed by optical coherence tomography at follow-up. Secondary endpoints will be the percentage of uncovered struts, and the percentage of struts with incomplete apposition. An ancillary study investigating the relation between systemic levels of endothelial progenitors cells and neointimal hyperplasia, and the interaction between endothelial progenitors cell levels and drug-eluting balloons has been planned. Thirty consecutive patients undergoing percutaneous coronary intervention will be randomized with a 1:1:1 design to bare-metal stent implantation alone (n = 10); bare-metal stent implantation after pre-dilation with a drug-eluting balloon (n = 10); or bare-metal stent implantation followed by post-dilation with a drug-eluting balloon (n = 10). Six-month follow-up coronary angiography with optical coherence tomography imaging of the stented segment will be performed in all patients. Blood samples for the assessment of endothelial progenitors cell levels will be collected on admission and at 6 months. DISCUSSION: Experimental and early clinical data showed that inhibition of neointimal hyperplasia may be obtained by local administration of antiproliferative drugs loaded on the surface of angioplasty balloons. The INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO) trial was conceived to test the superiority of a strategy of bare-metal stent implantation with additional drug-eluting balloon use (either before or after stenting) versus a strategy of bare-metal stent implantation alone for the reduction of neointimal hyperplasia. We also planned an ancillary study to assess the role of endothelial progenitors cells in the pathophysiology of neointimal hyperplasia. TRIAL REGISTRATION: Clinicaltrials.gov NCT01057563.