Objectives This study examined the impact of omentin on myocardial injury in a mouse model of ischemia/reperfusion (I/R) and explored its underlying mechanisms. Background Obesity is a major risk ...factor for ischemic heart disease. Omentin is a circulating adipokine that is down-regulated by obesity. Methods In patients who underwent successful reperfusion treatment after acute myocardial infarction, cardiac function and perfusion defect were assessed by using scintigraphic images. Mice were subjected to myocardial ischemia followed by reperfusion. Results This study found that high levels of plasma omentin were associated with improvement of heart damage and function after reperfusion therapy in patients with acute myocardial infarction. Systemic administration of human omentin to mice led to a reduction in myocardial infarct size and apoptosis after I/R, which was accompanied by enhanced phosphorylation of AMP-activated protein kinase (AMPK) and Akt in the ischemic heart. Fat-specific overexpression of human omentin also resulted in reduction of infarct size after I/R. Blockade of AMPK or Akt activity reversed omentin-induced inhibition of myocardial ischemic damage and apoptosis in mice. In cultured cardiomyocytes, omentin suppressed hypoxia/reoxygenation-induced apoptosis, which was blocked by inactivation of AMPK or Akt. Conclusions Our data indicate that omentin functions as an adipokine that ameliorates acute ischemic injury in the heart by suppressing myocyte apoptosis through both AMPK- and Akt-dependent mechanisms.
The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately.
In ...an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis.
Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.
Left Posterior Fascicle and Idiopathic Left VT. The left posterior fascicle may be a bystander of the circuit of verapamil‐sensitive idiopathic left ventricular tachycardia. During ventricular ...tachycardia (VT), 3 sequences of potentials were seen at the left posterior septum: diastolic Purkinje potentials propagating from base to apex and presystolic left posterior fascicular potentials and systolic left ventricular (LV) myocardial potentials propagating in the reverse direction. Selective capture of the left posterior fascicle by the sinus beat did not affect the VT cycle length. Entrainment pacing revealed that the retrograde limb of the circuit was not the left posterior fascicle, but the LV myocardium. (J Cardiovasc Electrophysiol, Vol. 23, pp. 556‐559, May 2012)
Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial ...infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI).
In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06).
Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.
CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.
Although epidemiologic studies have suggested that several genetic variants increase the risk of myocardial infarction, large-scale association studies that examine many polymorphisms simultaneously ...are required to allow reliable prediction of the genetic risk of myocardial infarction.
We used a fluorescence- or colorimetry-based allele-specific DNA-primer-probe assay system to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women).
In an initial screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects, 19 polymorphisms were selected in men and 18 in women by means of logistic-regression analysis, after adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the selected polymorphisms and the remaining 4152 subjects, similar logistic-regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (P<0.001) in men and the 4G-668/5G polymorphism in the plasminogen-activator inhibitor type 1 gene (P<0.001) and the 5A-1171/6A polymorphism in the stromelysin-1 gene (P<0.001) in women.
Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.
Objectives This study was designed to examine the protective effects of atrial natriuretic peptide (ANP) on contrast-induced nephropathy (CIN) after coronary angiography. Background Contrast-induced ...nephropathy is a common complication after angiography. Some studies have shown that ANP has renal protective effects, but the beneficial effects for CIN prevention remain to be clearly shown. Methods In a prospective, controlled, randomized trial in 254 consecutive patients with serum creatinine concentrations of ≥1.3 mg/dl, patients received either ANP (0.042 μg/kg/min; ANP group, n = 126) or Ringer solution alone (control group, n = 128). Treatment of either type was initiated 4 to 6 h before angiography and continued for 48 h. Results There were no significant differences in age, sex, diabetes mellitus, or baseline serum creatinine level between the 2 groups. The prevalence of CIN, defined as a 25% increase in creatinine or an increase in creatinine of ≥0.5 mg/dl from baseline within 48 h, was significantly lower in the ANP group than in the control group (3.2% vs. 11.7%, respectively; p = 0.015). Multivariate analysis revealed that the use of >155 ml of contrast medium (odds ratio: 6.89; p < 0.001) and ANP treatment (odds ratio: 0.24; p = 0.016) were significant predictors of developing CIN. The incidence of an increase in creatinine of ≥25% or of ≥0.5 mg/dl from baseline at 1 month was also significantly lower in the ANP group than in the control group (p = 0.006). Conclusions In addition to hydration, ANP administration is effective in the prevention of CIN in patients with chronic renal failure, and the effect was maintained for 1 month.
Abstract Background In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the ...Na+ /H+ exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI. Methods In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3–5 days after pPCI and safety up to 7 days. Results Baseline characteristics were similar in the two groups. MSI 3–5 days after pPCI (0.200 vs. 0.290, p = 0.56), 3 months after pPCI (0.470 vs. 0.500, p = 0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (≥38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p = 0.03). TY-51924 did not adversely influence hemodynamics. Conclusions TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow.
Abstract Background Anticoagulation therapy with the vitamin K antagonist (VKA) warfarin has been demonstrated to reduce thromboembolic risk after electrical cardioversion (ECV). However, data ...concerning ECV with non-VKA oral anticoagulants (NOACs) is limited. The objective of this study was to determine the efficacy and safety of NOACs in patients undergoing ECV in a real-world clinical practice at a single center in Japan. Methods We retrospectively analyzed the data of 406 consecutive patients who underwent ECV for atrial fibrillation (AF) or flutter under anticoagulation with one of the three NOACs ( n =149) or with a VKA ( n =257). Results The CHADS2 and HAS-BLED scores were significantly higher in the VKA group, whereas the NOACs group had a tendency toward greater spontaneous echo contrast grades. After ECV, ischemic stroke occurred in three patients of the VKA group and one patient in the NOAC group, all of whom had persistent AF, indicating no significant difference in the thromboembolic event rate within 30 days following ECV. No other thromboembolic events, major bleeding, or death occurred in either group. Among the NOAC and VKA patients in whom we newly introduced an oral anticoagulant to perform ECV, the number of days leading to ECV was significantly lesser for the NOAC patients. Conclusion NOACs may be used as an alternative to VKAs for ECV and may allow prompt ECV in clinical practices.
Adiponectin is an adipose-derived plasma protein that demonstrates beneficial actions on myocardial injury under ischemic conditions. Circulating endothelial progenitor cells are reported to ...associate with rescue of cardiac damage after acute myocardial infarction (AMI). We examined whether circulating adiponectin level affects myocardial function and injury in patients with AMI. A total of 48 patients who underwent successful reperfusion treatment after AMI were enrolled. Cardiac function and perfusion defect were assessed by scintigraphic images of iodine-123 β-methyl iodophenyl pentadecanoic acid in the acute phase and technetium-99m tetrofosmin in the long-term phase. Plasma adiponectin levels were measured by enzyme-linked immunosorbent assay at day 7 after AMI. Plasma adiponectin levels associated positively with myocardial salvage index representing the proportion of initial perfusion defect rescued by reperfusion and recovery of ejection fraction in the long-term phase and negatively with final infarct size. A positive correlation was also observed between adiponectin levels and number of circulating CD34+ cells as determined by flow cytometry and between myocardial salvage index and recovery of ejection fraction independently associated with circulating CD34+ cell levels. In conclusion, plasma adiponectin levels predict improvement of cardiac damage and function after reperfusion therapy in patients with AMI, suggesting that adiponectin could serve as a biomarker for assessment of myocardial injury after AMI.
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