Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

Myocardial salvage for ST-elevation myocardial infarction with terminal QRS distortion and restoration of brisk epicardial coronary flow.

Recently, it has been reported that large infarcts associated with terminal QRS distortion (QRSDIS) on the admission electrocardiograms of patients with ST-elevation myocardial infarctions (STEMIs) may be caused by a failure to achieve thrombolysis in myocardial infarction (TIMI) grade 3 flow after primary percutaneous coronary intervention (PCI). However, the relationship between QRSDIS and final infarct size when TIMI grade 3 flow could be achieved by primary PCI is still unclear. Sixty-two consecutive patients with first anterior STEMI and who achieved TIMI grade 3 flow by primary PCI were classified into two groups according to the presence (Group A, n = 18) or absence (Group B, n = 44) of QRSDIS. Two weeks after the onset of acute myocardial infarction, Group A had a larger left ventricular (LV) end-systolic volume index (LVESVI) and a lower LV ejection fraction (LVEF) than Group B (LVESVI: 38 +/- 13 vs 31 +/- 12 ml/m(2), P = 0.025: LVEF: 42% +/- 10% vs 51% +/- 10%, P = 0.004). Through multivariate analysis, independent predictors of poor LV systolic function (LVEF < 40%) were determined to be the presence of QRSDIS (odds ratio 21.04, P = 0.021) and proximal left anterior descending artery occlusion (odds ratio 16.15, P = 0.033). Myocardial damage could not be reduced in patients experiencing STEMI with QRSDIS, even when TIMI grade 3 flow could be achieved by primary PCI, as much as in patients experiencing STEMI without QRSDIS.

Isolated post-challenge hyperglycemia in patients with normal fasting glucose concentration exaggerates neointimal hyperplasia after coronary stent implantation.

Postprandial hyperglycemia has been shown to increase the risk of cardiovascular disease as much as overt diabetes mellitus does. The aim of this study was to determine whether isolated post-challenge hyperglycemia during an oral glucose tolerance test (OGTT) is related to exaggerated neointimal proliferation after coronary stent implantation. Forty seven coronary lesions treated with stents in 40 patients who had normal fasting glucose levels (<110 mg/dl) were categorized into the following 2 groups according to the results of a 75-g OGTT: 29 lesions in 24 patients with normal glucose tolerance (NGT group) and 18 lesions in 16 patients with abnormal glucose tolerance (AGT group). Although there were no differences in angiographic characteristics before and immediately after stenting between the 2 groups, the minimal lumen diameter was significantly smaller (p=0.04) and the degree of stenosis and late loss were also significantly greater (p=0.01 and p=0.047) in the AGT group than in the NGT group at 6-month follow-up. Multiple regression analysis including the insulin concentrations during an OGTT revealed that the 120-min plasma glucose concentration after glucose load significantly correlated with late loss (p=0.0018) and the degree of stenosis (p=0.0100) at follow-up. It is concluded that isolated post-challenge hyperglycemia exaggerates neointimal hyperplasia after coronary stent implantation.

Local delivery of low-dose docetaxel, a novel microtubule polymerizing agent, reduces neointimal hyperplasia in a balloon-injured rabbit iliac artery model.

OBJECTIVE: Docetaxel (DOC) is a novel microtubule polymerizing agent, with superior antiproliferative properties as compared to paclitaxel. DOC is therefore a potential therapeutic tool for the prevention of restenosis following angioplasty. However, DOC has systemic toxicity such as leukocytopenia, which occurs in a dose-dependent manner. To minimize such adverse effects, we carried out local delivery of low-dose DOC directly to injured vessel sites. METHODS: The rabbit iliac artery was denuded, and then DOC (2 mg) or control vehicle was administered locally 20 min, via a local drug delivery catheter. RESULTS: The levels of DOC in the plasma were within ng/ml range, eliminating hematopoietic side effects. Seven days after the local delivery (DOC: n=4, control: n=4), DOC decreased the number of Ki-67-labeled cells in the intima (DOC: 22 +/-10 vs. control: 66 +/- 18 cells/mm(2), P<0.01), indicating a decreased proliferative activity. At 28 days (DOC: n=8, control: n=8), computer-assisted morphometric analysis demonstrated that DOC significantly reduced the intimal area (DOC: 0.15 +/- 0.13 vs. control: 0.70 +/- 0.13 mm(2), P<0.01). There was also a decrease in medial area in the DOC-treated vessels (DOC: 0.62 +/- 0.17 vs. control: 1.13 +/- 0.38 mm(2), P<0.01). CONCLUSIONS: Local delivery of DOC, even after a single low-dose administration, effectively inhibits neointimal hyperplasia. Such administration is associated with a minimal likelihood of systemic adverse effects (leukocytopenia), but potentially induces local toxicity (a decrease in medial wall thickness) due to extensive cytotoxic effect.