Summary Background Compared with metallic drug-eluting stents, bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention. Whether ...or not these devices are as safe and effective as drug-eluting stents within the first year after implantation is unknown. Methods We did a patient-level, pooled meta-analysis of four randomised trials in which 3389 patients with stable coronary artery disease or a stabilised acute coronary syndrome were enrolled at 301 academic and medical centres in North America, Europe, and the Asia-Pacific region. These patients were randomly assigned to the everolimus-eluting Absorb BVS (n=2164) or the Xience cobalt-chromium everolimus-eluting stent (CoCr-EES; n=1225). The primary endpoints were the 1-year relative rates of the patient-oriented composite endpoint (all-cause mortality, all myocardial infarction, or all revascularisation) and the device-oriented composite endpoint of target lesion failure (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation). All analyses were by intention to treat. The four randomised trials included in our meta-analysis are all registered with ClinicalTrials.gov , numbers NCT01751906 , NCT01844284 , NCT01923740 , and NCT01425281. Findings The summary treatment effect for the 1-year relative rates of the patient-oriented composite endpoint did not differ significantly different between BVS and CoCr-EES (relative risk RR 1·09 0·89–1·34, p=0·38). Similarly, the 1-year relative rates of the device-oriented composite endpoint did not differ between the groups (RR 1·22 95% CI 0·91–1·64, p=0·17). Target vessel-related myocardial infarction was increased with BVS compared with CoCr-EES (RR 1·45 95% CI 1·02–2·07, p=0·04), due in part to non-significant increases in peri-procedural myocardial infarction and device thrombosis with BVS (RR 2·09 0·92–4·75, p=0·08). The relative rates of all-cause and cardiac mortality, all myocardial infarction, ischaemia-driven target lesion revascularisation, and all revascularisation did not differ between BVS and CoCr-EES. Results were similar after multivariable adjustment for baseline imbalances, and were consistent across most subgroups and in sensitivity analysis when two additional randomised trials with less than 1 year of follow-up were included. Interpretation In this meta-analysis, BVS did not lead to different rates of composite patient-oriented and device-oriented adverse events at 1-year follow-up compared with CoCr-EES. Funding Abbott Vascular.
Human pluripotent stem cell-derived cardiomyocytes (CMs) are a promising tool for cardiac cell therapy. Although transplantation of induced pluripotent stem cell (iPSC)-derived CMs have been reported ...in several animal models, the treatment effect was limited, probably due to poor optimization of the injected cells. To optimize graft cells for cardiac reconstruction, we compared the engraftment efficiency of intramyocardially-injected undifferentiated-iPSCs, day 4 mesodermal cells, and day 8, day 20, and day 30 purified iPSC-CMs after initial differentiation by tracing the engraftment ratio (ER) using in vivo bioluminescence imaging. This analysis revealed the ER of day 20 CMs was significantly higher compared to other cells. Transplantation of day 20 CMs into the infarcted hearts of immunodeficient mice showed good engraftment, and echocardiography showed significant functional improvement by cell therapy. Moreover, the imaging signal and ratio of Ki67-positive CMs at 3 months post injection indicated engrafted CMs proliferated in the host heart. Although this graft growth reached a plateau at 3 months, histological analysis confirmed progressive maturation from 3 to 6 months. These results suggested that day 20 CMs had very high engraftment, proliferation, and therapeutic potential in host mouse hearts. They also demonstrate this model can be used to track the fate of transplanted cells over a long time.
Background:Patients with severe aortic stenosis (AS) might be at high risk for adverse cardiovascular events at the time of non-cardiac surgery.Methods and Results:The current study population ...included 348 patients who underwent elective non-cardiac surgery under general or spinal anesthesia during the follow up of 3,815 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry. There were 187 patients with untreated severe AS at time of surgery (untreated severe AS group) and 161 patients who had undergone aortic valve replacement (AVR) before surgery (prior AVR group), including 23 patients with prophylactic AVR. The primary outcome measure was 30-day mortality after non-cardiac surgery. At 30 days after non-cardiac surgery, 8 patients (4.3%) died in the untreated severe AS group, while no patients died in the prior AVR group (P=0.008). The causes of death were cardiovascular in 6 out of 8 patients. Mortality at 30 days was higher in untreated severe AS patients with AS-related symptoms before surgery than in those without AS-related symptoms (7.2% vs. 3.1%). Higher surgical risk estimates of the non-cardiac surgery incrementally increased the risk of 30-day mortality in patients with untreated severe AS, though the difference was not statistically significant (low-risk: 0%, intermediate-risk: 4.3%, and high-risk: 6.6 %, P=0.46).Conclusions:Symptomatic and asymptomatic severe AS might be associated with higher risk of 30-day mortality if untreated before elective intermediate- and high-risk non-cardiac surgery, while no patient with prior AVR died after elective non-cardiac surgery.
RATIONALE:In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic ...cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated.
OBJECTIVE:To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM.
METHODS AND RESULTS:C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in neonatal rat cardiac myocytes and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cardiomyocyte-specific miR-451 knockout mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in cardiomyocyte-specific miR-451 knockout mouse hearts compared with control mouse hearts.
CONCLUSIONS:Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway.
Abstract Effects of daily fluctuation of ambient temperature and concentrations of air pollutants on acute cardiovascular events have not been well studied. Between January 2011 and December 2012, a ...total of 56,863 consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention were registered from 929 institutes with median inter-institutional distance of 2.6 km. We constructed generalized linear mixed models in which presence or absence of STEMI patients per day per institute was included as a binomial response variable, with daily meteorological and environmental data obtained from their respective observatories nearest to the institutes (median distance of 9.7 km and 5.6 km) as the explanatory variables. Both lower mean temperature, and increase in maximum temperature from the previous day were independently associated with the STEMI occurrence throughout the year (OR 0.92595%CI 0.915-0.935, per10°C, P<0.001, and OR 1.01295%CI 1.009-1.015, per°C, P<0.001, respectively). Decrement in minimum temperature from -4 day to -3 day before the event date was marginally associated with the STEMI occurrence, only during the wintertime (OR 0.99195%CI 0.982-0.999, per°C, P=0.03). As for the air pollutants, nitrogen oxides and suspended particle matter were not correlated with the occurrence of STEMI after adjusting for the meteorological and livelihood variables. Both the absolute value and relative change in the ambient temperature were associated with the occurrence of STEMI; the associations with the air pollutant levels were less clear after adjustment for these meteorological variables in Japan.
Background:There is a scarcity of data on short-duration dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy as compared with aspirin monotherapy after percutaneous coronary ...intervention (PCI).Methods and Results:STOPDAPT-1 is a prospective trial enrolling patients who agreed to 3-month DAPT followed by aspirin monotherapy after everolimus-eluting stent (EES) implantation. STOPDAPT-2 is a randomized trial comparing 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after EES implantation. We compared the clinical outcomes of patients assigned to the 1-month DAPT group in STOPDAPT-2 and the 3-month DAPT group enrolled in STOPDAPT-1. The current study population consisted of 1,480 patients in STOPDAPT-2 and 1,339 patients in STOPDAPT-1. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis and TIMI major/minor bleeding. Cumulative 1-year incidence of the primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (2.3% vs. 2.3%, P=0.98). After adjusting for confounders, there was no excess risk of STOPDAPT-2 relative to STOPDAPT-1 for the primary endpoint. Between 3 and 12 months, the cumulative incidence of primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (1.7% vs. 1.6%, P=0.77).Conclusions:The effect of 1-month DAPT followed by clopidogrel monotherapy on clinical outcomes was similar to that of 3-month DAPT followed by aspirin monotherapy in patients receiving PCI.
PDF
