Impact of hemodialysis on local vessel healing and thrombus formation after drug-eluting stent implantation

AbstractBackgroundAlthough hemodialysis (HD) is a suggested risk factor for stent thrombosis, its contribution to local vessel healing after drug-eluting stent (DES) implantation is unclear.MethodsA total of 121 patients (152 lesions treated with DES) who underwent 8-month follow-up coronary angiography with optical coherence tomography (OCT) were enrolled, and the findings were compared between patients with and without HD. To match baseline differences, mid-term OCT findings of 42 propensity score-matched lesions (21 non-HD vs. 21 HD) were compared. Effects of HD on the efficacy of antiplatelet therapy were also evaluated by VerifyNow assay (Accumetrics, San Diego, CA, USA).ResultsPatients with HD had a significantly higher rate of thrombus formation than those without (64% vs. 33%, p=0.007), although the baseline parameters and lesion characteristics differed between the groups. Multivariate logistic regression analysis revealed that HD was associated with an increased risk of thrombus formation (odds ratio 5.991, 95% confidence interval: 1.972–18.199, p=0.002). Even after propensity-matching for patient background and balancing of angiographic and OCT variables, the risk of thrombus formation remained significantly higher in HD patients. The P2Y12-reaction unit was significantly increased after HD (Pre HD: 211±75 vs. Post HD: 262±59, p=0.01), but patients without HD showed no increase during the same elapsed time (221±88 vs. 212±96, p=0.19).ConclusionsHD is a potential risk factor for subclinical thrombus attachment after DES therapy. Systemic problems, such as residual platelet reactivity, associated with HD as well as local vessel features in HD patients might contribute to the increased incidence of thrombus attachment and subsequent onset of thrombotic event after DES implantation

Effect of Daily Glucose Fluctuation on Coronary Plaque Vulnerability in Patients Pre-Treated With Lipid-Lowering Therapy A Prospective Observational Study

AbstractObjectivesThis study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy.BackgroundThere is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD.MethodsThis prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated.ResultsIn total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007).ConclusionsDaily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients

PlGF Repairs Myocardial Ischemia through Mechanisms of Angiogenesis, Cardioprotection and Recruitment of Myo-Angiogenic Competent Marrow Progenitors

Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected.We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease

Cardiomyocyte Formation by Skeletal Muscle-Derived Multi-Myogenic Stem Cells after Transplantation into Infarcted Myocardium

BACKGROUND: Cellular cardiomyoplasty for myocardial infarction has been developed using various cell types. However, complete differentiation and/or trans-differentiation into cardiomyocytes have never occurred in these transplant studies, whereas functional contributions were reported. METHODS AND RESULTS: Skeletal muscle interstitium-derived CD34(+)/CD45(-) (Sk-34) cells were purified from green fluorescent protein transgenic mice by flowcytometory. Cardiac differentiation of Sk-34 cells was examined by in vitro clonal culture and co-culture with embryonic cardiomyocytes, and in vivo transplantation into a nude rat myocardial infarction (MI) model (left ventricle). Lower relative expression of cardiomyogenic transcription factors, such as GATA-4, Nkx2-5, Isl-1, Mef2 and Hand2, was seen in clonal cell culture. However, vigorous expression of these factors was seen on co-culture with embryonic cardiomyocytes, together with formation of gap-junctions and synchronous contraction following sphere-like colony formation. At 4 weeks after transplantation of freshly isolated Sk-34 cells, donor cells exhibited typical cardiomyocyte structure with formation of gap-junctions, as well as intercalated discs and desmosomes, between donor and recipient and/or donor and donor cells. Fluorescence in situ hybridization (FISH) analysis detecting the rat and mouse genomic DNA and immunoelectron microscopy using anti-GFP revealed donor-derived cells. Transplanted Sk-34 cells were incorporated into infarcted portions of recipient muscles and contributed to cardiac reconstitution. Significant improvement in left ventricular function, as evaluated by transthoracic echocardiography and micro-tip conductance catheter, was also observed. CONCLUSIONS AND SIGNIFICANCE: Skeletal muscle-derived multipotent Sk-34 cells that can give rise to skeletal and smooth muscle cells as reported previously, also give rise to cardiac muscle cells as multi-myogenic stem cells, and thus are a potential source for practical cellular cardiomyoplasty

Outcomes of single-stage total arch replacement via clamshell incision

<p>Abstract</p> <p>Background</p> <p>Treatment of complex aortic pathologies involving the transverse arch with extensive involvement of the descending aorta remains a surgical challenge. Since clamshell incision provides superior exposure of the entire thoracic aorta, we evaluated the use of this technique for single-stage total arch replacement by arch vessel reconstruction.</p> <p>Methods</p> <p>The arch-first technique combined with clamshell incision was used in 38 cases of aneurysm and aortic disease in 2008 and 2009. Extensive total arch replacement was used with clamshell incision for reconstruction of arch vessels under deep hypothermic circulatory arrest.</p> <p>Results</p> <p>Overall 30-day mortality was 13%. The mean operating time was approximately 8 hours. Deep hypothermia resulted in mean CPB time exceeding 4.5 hours and mean duration of circulatory arrest was 25 minutes. The overall postoperative temporary and permanent neurologic dysfunction rates were 3% and 3% for elective and 3% and 0% for emergency surgery, respectively. All patients except the five who died in hospital were discharged without nursing care after an average post-operative hospital stay of 35 days.</p> <p>Conclusions</p> <p>The arch-first technique, combined with clamshell incision, provides expeditious replacement of the thoracic aorta with an acceptable duration of hypothermic circulatory arrest and minimizes the risk of retrograde atheroembolism by using antegrade perfusion.</p