Abstract Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile ...microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo . The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.
A cohort of patients who underwent stent implantation for unprotected left main coronary artery disease was compared with a propensity-matched cohort of patients who underwent coronary-artery bypass ...grafting. The risk of death and the composite outcome of death, Q-wave myocardial infarction, or stroke did not differ significantly between the two groups. The risk of target-vessel revascularization was higher in the group that received stents.
The risk of death and the composite outcome of death, Q-wave myocardial infarction, or stroke did not differ significantly between the two groups. The risk of target-vessel revascularization was higher in the group that received stents.
Significant narrowing of the left main coronary artery puts a patient at high risk, since it can jeopardize the entire myocardium of the left ventricle, and it has the worst prognosis of any form of coronary artery disease.
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On the basis of clinical trials that show a survival benefit with bypass surgery as compared with medical treatment,
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coronary-artery bypass grafting (CABG) has been considered standard therapy for patients with left main coronary artery disease and is recommended by current practice guidelines.
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Because of concern about procedural risk and long-term durability, percutaneous coronary intervention (PCI) usually has been restricted . . .
Background
Hypothyroidism has been known to be associated with hyperlipidemia, endothelial dysfunction and atherosclerosis. Elevation of thyroid‐stimulation hormone (TSH) is a gold standard to detect ...these conditions. However, no large studies have investigated the association between TSH elevation and long‐term clinical outcomes in patients with acute myocardial infarction (AMI).
Hypothesis
Hypothyroidism is associated with higher mortality in patients with AMI.
Methods
A total of 4748 AMI patients undergoing percutaneous coronary intervention (PCI) with drug‐eluting stents were consecutively enrolled. We analyzed 1977 patients whose thyroid function data available after the exclusion of hyperthyroidism and possible central hypothyroidism. Patients were divided into two groups; euthyroid group (n = 1846) with normal TSH and normal free thyroxine (FT4); hypothyroidism group (n = 131) with elevated TSH and normal or low FT4. The two groups were subsequently compared with their all‐cause and cardiac mortalities.
Results
Median follow‐up duration was 3.5 years. Hypothyroidism group were older, included in more females, and had higher incidences of atrial fibrillation, stroke, and renal dysfunction. Elevated TSH was associated with significantly higher all‐cause mortality (26.0% vs 11.7%, P < 0.0001) and cardiac mortality (9.2% vs 4.6%, P = 0.014). The multivariate Cox proportional hazards model identified that TSH elevation was a significant predictor of all‐cause mortality (adjusted hazard ratio 1.560, 95% confidence interval 1.017 to 2.392, P = 0.041).
Conclusions
Our data suggest that AMI patients with TSH elevation had worse clinical outcome. Moreover, TSH elevation was a predictor of all‐cause mortality in patients with AMI.
Stent thrombosis (ST) remains a catastrophic problem in patients undergoing percutaneous coronary intervention (PCI). However, a paucity of data exist regarding the incidence, implications, and ...predictors of ST in patients with acute myocardial infarction (AMI). We consecutively enrolled patients with AMI in the CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI registry who underwent PCI from January 2004 to December 2009 and analyzed definite or probable ST according to Academic Research Consortium definitions. The median follow-up duration was 41.9 months. Definite or probable ST occurred in 136 patients (3.7%), including 44 with early ST (1.0%), 38 with late ST (0.9%), and 54 with very late ST (2.0%). The annual incidence of very late ST ranged from 0.5% to 0.6%. The all-cause mortality rate after ST was 29%, which was higher than that for patients without ST (17%; p <0.001). The independent predictors of ST were no-reflow phenomenon (hazard ratio HR 1.96, 95% confidence interval CI 1.28 to 3.03), decreased left ventricular ejection fraction (HR 1.70, 95% CI 1.21 to 2.40), anemia (HR 1.54, 95% CI 1.09 to 2.18), and a mean stent diameter <3.0 mm (HR 1.53, 95% CI 1.04 to 2.27). ST is not uncommon in patients with AMI and continues to occur beyond 1 year after PCI, irrespective of the stent type or clinical presentation. Patients with ST are associated with higher mortality than patients without ST. No reflow, decreased left ventricular ejection fraction, anemia, and a mean stent diameter <3.0 mm are independent predictors of ST.
Stent length has been considered an important predictor of adverse events after percutaneous coronary intervention, even with the first-generation drug-eluting stents (DESs). The introduction of ...newer-generation DES has further reduced the rates of adverse clinical events such as restenosis, myocardial infarction, and stent thrombosis. The aim of this study was to compare the impact of stent length on the long-term clinical outcomes between first- and newer-generation DESs. The effects of stent length (≥32 vs <32 mm) on the clinical outcomes were evaluated in 8,445 patients who underwent percutaneous coronary intervention using either a first-generation DES (sirolimus- and paclitaxel-eluting stents, n = 6,334) or a newer-generation DES (everolimus- and zotarolimus-eluting stents, n = 2,111) from January 2004 to December 2009. The 3-year adverse outcomes (composite of all-cause death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis) were compared using the inverse probability of treatment-weighted method according to the stent length. After adjustment for differences in the baseline risk factors, a stent length of ≥32 mm was significantly associated with higher cumulative rates of target vessel revascularization and stent thrombosis in the patients treated with a first-generation DES (adjusted hazard ratio 1.875, 95% confidence interval 1.531 to 2.297, p <0.001; adjusted hazard ratio 2.964, 95% confidence interval 1.270 to 6.917, p = 0.012), but it was not associated with the clinical outcomes in patients treated with a newer-generation DES. In conclusion, stent length might not be associated with long-term clinical outcomes in newer-generation DES era, whereas stent length might be associated with long-term clinical outcomes in the first-generation DESs.
H2A.Z is a highly conserved H2A variant, and two distinct H2A.Z isoforms, H2A.Z.1 and H2A.Z.2, have been identified as products of two non-allelic genes, H2AFZ and H2AFV. H2A.Z has been reported to ...be overexpressed in breast, prostate and bladder cancers, but most studies did not clearly distinguish between isoforms. One recent study reported a unique role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. Here we first report that H2A.Z.1 plays a pivotal role in the liver tumorigenesis by selectively regulating key molecules in cell cycle and epithelial-mesenchymal transition (EMT). H2AFZ expression was significantly overexpressed in a large cohort of hepatocellular carcinoma (HCC) patients, and high expression of H2AFZ was significantly associated with their poor prognosis. H2A.Z.1 overexpression was demonstrated in a subset of human HCC and cell lines. H2A.Z.1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins and caused apoptotic cell death of HCC cells. We also observed that H2A.Z.1 knockdown reduced the metastatic potential of HCC cells by selectively modulating epithelial-mesenchymal transition regulatory proteins such as E-cadherin and fibronectin. In addition, H2A.Z.1 knockdown reduced the in vivo tumor growth rate in a mouse xenograft model. In conclusion, our findings suggest the oncogenic potential of H2A.Z.1 in liver tumorigenesis and that it plays established role in accelerating cell cycle transition and EMT during hepatocarcinogenesis. This makes H2A.Z.1 a promising target in liver cancer therapy.
We investigated the association between diabetes duration and the extent and severity of coronary artery disease (CAD) as well as long-term clinical outcomes using coronary computed tomography ...angiography (CCTA) in asymptomatic type 2 diabetic patients.
We analysed 933 asymptomatic type 2 diabetic patients without known CAD who underwent CCTA. Patients were divided into three groups according to the duration of diabetes: <5 years, 5-10 years, and ≥10 years. Stenosis by CCTA was scored as none (0%), non-obstructive (1-49%), or obstructive (≥50%) for each coronary artery segment. For these patients, we compared the prevalence, extent, and severity of CAD, including coronary artery calcium score (CACS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS). Major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, non-fatal myocardial infarction, and stroke, within a follow-up period were also compared.Patients with longer duration of diabetes possessed higher rates of obstructive CAD (P < 0.001). Patients with longer duration of diabetes also manifested greater degree of CACS, ABOS, SIS, and SSS (P < 0.001 for all) with associated higher rate of MACCE (P = 0.025). Presence of obstructive CAD as assessed by CCTA was an independent predictor of MACCE after adjusting for confounding risk factors (hazard ratio: 1.979, confidence interval: 1.178-3.327, P = 0.010).
In asymptomatic diabetic patients, longer diabetes duration is associated with a higher prevalence, extent, and severity of CAD as well as risk of MACCE. Moreover, greater CAD burden increases the risk of MACCE independent of co-existing CAD risk factors.
We performed the long-term follow-up of a large cohort of patients in a multicenter study receiving left main coronary artery (LMCA) revascularization.
Limited information is available on long-term ...outcomes for patients with unprotected LMCA disease who underwent coronary stent procedure or coronary artery bypass grafting (CABG).
We evaluated 2,240 patients with unprotected LMCA disease who received coronary stents (n = 1,102; 318 with bare-metal stents and 784 with drug-eluting stents) or underwent CABG (n = 1,138) between 2000 and 2006 and for whom complete follow-up data were available for at least 3 to 9 years (median 5.2 years). The 5-year adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction MI, or stroke; and target vessel revascularization TVR) were compared with the use of the inverse probability of treatment weighted method and propensity-score matching.
After adjustment for differences in baseline risk factors with the inverse probability of treatment weighting, the 5-year risk of death (hazard ratio HR: 1.13; 95% confidence interval CI: 0.88 to 1.44, p = 0.35) and the combined risk of death, Q-wave MI, or stroke (HR: 1.07; 95% CI: 0.84 to 1.37, p = 0.59) were not significantly different for patients undergoing stenting versus CABG. The risk of TVR was significantly higher in the stenting group than in the CABG group (HR: 5.11; 95% CI: 3.52 to 7.42, p < 0.001). Similar results were obtained in comparisons of bare-metal stent with concurrent CABG and of drug-eluting stent with concurrent CABG. In further analysis with propensity-score matching, overall findings were consistent.
During 5-year follow-up, stenting showed similar rates of mortality and of the composite of death, Q-wave MI, or stroke but higher rates of TVR as compared with CABG for patients with unprotected LMCA disease.
Blood transcriptome reflects the status of diseases, and characteristic molecular signature provides a novel window on gene expression preceding acute coronary events. We aim to determine blood ...transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI). We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: STEMI (n = 10), Non-ST-segment-elevation MI (NSTEMI, n = 10) and unstable angina (UA, n = 11). Blood transcriptome scans revealed that a characteristic gene expression change exists in STEMI, resulting in 531 outlier genes as STEMI molecular signature (Welch's t test, P < 0.05). Another analysis with a set of blood samples of patients with STEMI (n = 7) before and 7 days after the primary percutaneous coronary intervention (n = 7) and normal control (n = 10) evidenced that STEMI molecular signature directly reflects the onset of STEMI pathogenesis. From the two sets of transcriptome-based STEMI signatures, we identified 10 genes encoding transmembrane or secretory proteins that are highly expressed in STEMI. We validated blood protein expression levels of these 10 putative biomarkers in 40 STEMI and 32 healthy subjects by ELISA. Data suggested that PGLYRP1, IRAK3 and VNN3 are more specific and sensitive diagnostic biomarkers for STEMI than traditional CK-MB or troponin.Blood transcriptome scans of ACS evidenced early stage molecular markers for STEMI. Here, we report novel biomarkers to diagnose STEMI at emergency department in hospitals by a simple ELISA method.
Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if ...multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low‐density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow‐up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least‐Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were −19.3 (2.68) mm Hg and −6.69 (2.76) mm Hg. The difference between the two groups was significant (−12.60 (2.77) mm Hg, 95% CI −18.06 to −7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were −52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (−55.13 (3.20) %, 95% CI −61.45 to −48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.
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