Meta-Analysis of Atrial Fibrillation and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is common in heart failure with preserved ejection fraction (HFpEF); However, the prognostic impact of AF on HFpEF patients has not been fully elucidated. METHODS: A literature search of the PubMed and EMBASE databases on literature published through April 2019 was undertaken. Combined hazard ratio (HR) estimates and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, depending on the heterogeneity. Subgroup analyses, sensitivity analysis and meta-regression analyses were also performed. RESULTS: Fourteen (14) eligible studies with 1,948,923 patients with HFpEF were included in the analysis. Atrial fibrillation was associated with an 11% increased risk of all-cause mortality in patients with HFpEF (HR 1.11, 95% CI 1.09-1.12). Sensitivity analysis confirmed the stability of the results. The stratification of studies by controlled or uncontrolled confounding factors affected the final estimate (confounder-controlled HR 1.21, 95% CI 1.12-1.30; confounder-uncontrolled HR 1.13, 95% CI 0.96-1.31). In addition, AF was an independent predictor of hospitalisation for heart failure (HR 1.32, 95% CI 1.15-1.52), cardiovascular death (HR 1.38, 95% CI 1.01-1.89) and stroke (HR 1.87, 95% CI 1.54-2.27). CONCLUSIONS: Atrial fibrillation was associated with worse clinical outcomes in patients with HFpEF. Further investigation is required to see whether AF is the primary offender in these patients or merely a bystander to worse diastolic function.

Meta-Analysis of the Impact of Pre-Procedural Serum Albumin on Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.

Pre-procedural serum albumin's impact on prognosis after transcatheter aortic valve replacement (TAVR) has been studied. Literature on the prognostic role of serum albumin in the survival of patients undergoing TAVR shows conflicting results. This meta-analysis was conducted to evaluate the impact of pre-procedural serum albumin on outcomes after TAVR. A comprehensive literature search of EMBASE, MEDLINE, and the Cochrane Library was undertaken through July 2019. The primary end points were 30-day and one-year all-cause mortality after TAVR. Risk ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effect model. Ten eligible studies with 8,236 patients were analyzed. Of the 8,236 patients undergoing TAVR, with a mean age of 83 years, 48.8% were men and were categorized into two groups according to low and normal serum albumin (cut-off value: 3.5 or 4 g/dL). Overall, low albumin was significantly associated with an approximately two-fold increase in 30-day all-cause mortality (HR, 2.09; 95% CI, 1.53-2.86) and a 61% increase risk for one-year mortality (HR, 1.61; 95% CI, 1.31-1.98) in patients after TAVR. Sensitivity analyses showed the results to be robust. The association of low albumin level with an increase in one-year mortality risk was not modified by study design, albumin cut-off value, Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM), and study quality. In conclusion, low albumin levels were associated with poor prognosis in patients after TAVR. Pre-procedural albumin can be used as a simple tool related to prognosis after TAVR.

Demography and welfare status of free-roaming dogs in Yangmingshan National Park, Taiwan.

Free-roaming dogs (Canis familiaris) cause threats to native wildlife and public health and raise concerns for their welfare. Understanding the demography of free-roaming dog populations is essential for developing an effective management plan. An evaluation of their welfare status would be beneficial to earn public support for the management plan. In this study, we estimated the population size, survivorship, and health of a free-roaming dog population in Yangmingshan National Park (YMSNP), Taiwan, during 2016-2018. YMSNP is a rural area with human settlements but also a protected area of conservation concern. We identified 191, 176, 216 individuals at our sampling sites in 2016, 2017, and 2018, respectively. Using a photographic capture-recapture method and extrapolation, we estimated that there were 786-979 dogs in the park during this 3-year period. The annual apparent survival rate of identified dogs was 16.7% for 2016-2017 and 23.9% for 2017-2018. The dogs had a high rate of lameness and dermatosis of 5.1-8.8% and 14.2-18.1%, respectively. Thirty-five blood samples showed that 34.3% of the dogs were anemic, 37.1% showed abnormal white blood cell counts, and 68.6% exhibited abnormal platelet counts. These results suggested that the dogs were at high density with low survivorship and in poor health, and new individuals entered the population continuously. Interventions to manage this dog population and to improve their welfare must be carried out. Our study provides an example for monitoring and managing a free-roaming dog population in a rural, conservation area in Southeast Asia.

Effectiveness and Safety of Warfarin in Dialysis Patients With Atrial Fibrillation: A Meta-Analysis of Observational Studies.

In routine practice, warfarin is widely used in dialysis patients with atrial fibrillation (AF) for stroke prevention though the ratio of risks to benefits remains unclear. Recent cohort studies investigating the association between warfarin use and the risks of stroke and bleeding in dialysis patients with AF present conflicting results. The objective of this study was to assess the effectiveness and safety of warfarin use in patients with AF undergoing dialysis. Three databases PubMed, EMBASE, and OVID were searched from their inception to August 2015. Observational studies which assessed the ischemic stroke or bleeding risk of warfarin use in dialysis patients with AF were included. Two reviewers independently extracted data and assessed methodological quality based on the Newcastle-Ottawa Scale score. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model and heterogeneity was assessed based on the Cochrane Q-statistic test and the I statistic. Metaregression analyses were performed to explore the source of heterogeneity. A total of 11 eligible studies with 25,407 patients were included in the analysis. Warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for ischemic stroke (HR 0.95, 95% CI 0.66-1.35). Sensitivity analyses found results to be robust. Metaregression analysis showed that demographic feature, clinical characteristics, or study-level variable had no impact of warfarin use on stroke risk. In addition, warfarin use was associated with a 27% higher risk for bleeding (95% CI 1.04-1.54). Overall, warfarin use did not have a significant association with reduced mortality (95% CI 0.96-1.11). It appears that warfarin use is not beneficial in reducing stroke risk, but with a high risk for bleeding in dialysis patients with AF. Randomized trials are needed to determine the risk-benefit ratio of warfarin in dialysis patients with AF.

Efficacy and safety of low-dose clopidogrel after 12-month dual antiplatelet therapy for patients having drug-eluting stent implantation.

BACKGROUND: To prevent stent thrombosis (ST) after implantation of drug-eluting stents (DESs) in patients with coronary heart disease, 12-month dual antiplatelet therapy (DAPT) is recommended. However, the optimal long-term antiplatelet regimen is not clear for the patients who have completed the 12-month DAPT. METHODS: We reviewed the data of 755 consecutive patients who had undergone percutaneous coronary intervention (PCI) three years ago and completed 12-month DAPT. They were divided into three groups according to the antiplatelet medication they had used for two years after 12-month DAPT [low-dose clopidogrel (Talcom(®), 25mg/d), clopidogrel (Plavix(®), 75mg/d) and aspirin (100 mg/d)]. The efficacy (a composite incidence of cardiac death, myocardial infarction and target vessel revascularization) and safety (incidences of bleeding, gastrointestinal trouble and drug discontinuation) were compared among the three groups. RESULTS: The rates of multi-vessel lesions, prior MI, hemoglobin A1C (HbA1c) and low-density lipoprotein cholesterol were significantly higher in the clopidogrel (75 mg/day) group than in the other two groups (P>0.05 for both comparisons). There was no significant difference in the overall composite incidence of cardiac death, myocardial infarction and target vessel revascularization in the three groups at three years after PCI. The rates of bleeding (especially minor bleeding), gastrointestinal trouble, drug discontinuation and any blood transfusion were markedly lower in the low-dose clopidogrel (25 mg/d) group than in the other two treatment groups (P<0.05). CONCLUSIONS: The 25-mg maintenance dose of clopidogrel after 12-month DAPT may be more preferable to Chinese patients who have undergone DES implantation, because of its lower cost but no less efficacy and safety.

Transplantation of human umbilical cord-derived endothelial progenitor cells promotes re-endothelialization of the injured carotid artery after balloon injury in New Zealand white rabbits.

BACKGROUND: Cell transplantation has great potential for promoting endothelial repair and reducing the complications of percutaneous coronary intervention (PCI). The aim of this study was to investigate the effect of transplantation of human umbilical cord blood endothelial progenitor cells (EPCs) on injured arteries. METHODS: Umbilical cord blood mononuclear cells were obtained from post-partum lying-in women, and EPCs were isolated, cultured, expanded and identified by immunofluorescence. The carotid arterial endothelium of New Zealand white rabbits was injured by dilatation with a 3F balloon, and the EPCs were injected into the lumen of the injured artery in the transplanted group (n = 16), while an equal volume of phosphated buffered saline (PBS) was injected into the control group after balloon injury (n = 16). The animals were sacrificed after either 2 or 4 weeks, and the grafted cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibodies. Arterial cross sections were analyzed by pathology, immunohistochemistry and morphometry to evaluate the reparative effects of EPCs. Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF)-ß1 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fluorescence-labeled EPCs were found in the neointima. The neointimal area and the neointimal/medial area ratio were significantly lower in the transplanted group than in the control group (P < 0.05). von Willebrand factor (vWF) immunohistostaining showed more VWF-positive cells in the transplanted animals than in the controls (8.75 ± 2.92 vs. 4.50 ± 1.77, P < 0.05). Compared with the control group, the transplanted group had lower expression of PCNA mRNA (0.67 ± 0.11 vs. 1.25 ± 0.40, P < 0.01) and higher expression of TGF-ß1 mRNA (1.10 ± 0.21 vs. 0.82 ± 0.07, P < 0.05). CONCLUSIONS: EPCs derived from human umbilical cord blood were successfully transplanted into injured vessels. The transplanted EPCs inhibited neointimal hyperplasia and promoted vascular re-endothelialization.

Pregnancy-associated plasma protein predicts outcomes of percutaneous coronary intervention in patients with non-ST-elevation acute coronary syndrome.

OBJECTIVE: Pregnancy-associated plasma protein A (PAPP-A) may play an important role in the development of acute coronary syndrome. This study aimed to investigate the relationship between the levels of circulating PAPP-A and the mid-term outcomes of percutaneous coronary intervention (PCI) in patients with non-ST-elevation acute coronary syndrome. METHODS: The circulating PAPP-A levels and high-sensitivity C-reactive protein before PCI were measured in 129 patients with single coronary artery stenosis. The end point of clinical follow-up was cardiac death, nonfatal myocardial infarction, target vessel revascularization, and rehospitalization for angina. RESULTS: During the follow-up of an average of 20.3 ± 5.2 months, a cardiac event was recorded in 25 patients (19.4%). The levels of PAPP-A (29.85 ± 19.51 mIu/L vs 20.47 ± 14.33 mIu/L, P = .007) and high-sensitivity C-reactive protein (5.63 ± 2.13 mg/L vs 4.11 ± 1.28 mg/L, P = .014) in patients with cardiac events were higher than in those without cardiac events. PAPP-A ≥ 11.33 mIu/L has a strong predictive value for a combined end point (risk ratio = 4.1; 95% confidence interval, 1.0-16.2; P = .037). Patients with lower PAPP-A levels (<11.33 mIu/L) had higher event-free survivals than patients with higher PAPP-A levels (log rank = 9.334, P = .025). CONCLUSION: Circulating PAPP-A levels predict the mid-term outcomes of PCI in patients with non-ST-elevation acute coronary syndrome and single-vessel stenosis.

Expanded human cord blood-derived endothelial progenitor cells salvage infarcted myocardium in rats with acute myocardial infarction.

1. Cell transplantation has promise as a therapeutic option for restoring impaired heart function after acute myocardial infarction (AMI). However, the optimal cell type to use remains controversial. We investigated the therapeutic efficacy and feasibility of intramyocardial transplantation of human umbilical cord blood-derived endothelial progenitor cells (hUCB-EPC) in rats with AMI. 2. The Wistar rats myocardial infarction model was established by ligating the left anterior descending artery. The labelled hUCB-EPC were transplanted through intramyocardial injection. Left ventricular function was assessed using a pressure-volume catheter and echocardiogram. Anti-VIII immunohistochemistry staining was used to reflect the degree of angiogenesis in peri-infarcted areas by calculating the average capillary density. The fibrosis degree of infarcted myocardium was analysed by Masson staining and the collagen volume fraction was calculated. 3. The labelled donor endothelial progenitor cells were detected in the new microvessels in host myocardium by double-positive staining with CM-Dil and FITC-UEA-l. An increase in left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-systolic pressure, first derivative of left ventricular pressure (+dP/dtmax and -dP/dtmax), as well as a decrease in the left ventricular end-diastolic pressure in rats with cell therapy indicated a significant improvement in global heart function. The cell therapy group had increased microvessel formation and a decreased degree of myocardial fibrosis compared to the control group. Moreover, the degree of myocardial fibrosis was less than that of the control group. 4. The improved global heart function and decreased cardiac fibrosis in rats with AMI implies the potential benefit of hUCB-EPC transplantation.

Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction.

BACKGROUND: Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction. METHODS: Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-l). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization. RESULTS: The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted rats, associated with a significant improvement of global heart function in terms of the increase of left ventricular end-systolic pressure (LVESP), +dp/dtmax and -dp/dtmax as well as the decrease of LVEDP in rats with EPCs therapy comparing to the control rats (P < 0.05). Moreover, the expression of the rat PCNA mRNA and PECAM were both enhanced in the EPCs group compared with that of the control group. CONCLUSIONS: The human umbilical cord blood-derived EPCs could incorporate into new-born capillaries in rat myocardium, induce revascularization and improve the proliferation activity in the peri-infarct area, resulting in the improvement of global heart function. This may indicate a promising stem cell resource in cell-based therapy for ischaemic diseases.

Isolation and characterization of polymorphic microsatellite loci from Areca catechu (Arecaceae) using PCR-based isolation of microsatellite arrays.

Betel nut (Areca nut, Areca catechu L.) is a conspicuous and important cultivated plant of tropical and subtropical habitats throughout Southeast Asia and Oceania. As a significant cultural and social offering, the migration of betel nut associated with human dispersal is an important issue in ethnobotany and anthropology. In this study, we described the development of nine microsatellite loci from A. catechu. The number of alleles per locus ranged from 5 to 15. The expected and observed heterozygosities ranged from 0.71to 0.94 and from 0 to 0.88, respectively. All microsatellite loci, except for AC30, significantly deviated from Hardy-Weinberg equilibrium possibly due to artificially selected cultivation or the existence of excessive null alleles. No linkage disequilibrium was observed from pairwise comparisons of loci, except for AC06 and AC08.

[Beneficial effects of human umbilical cord blood mononuclear cells transplantation on rats with experimental myocardial infarction].

OBJECTIVE: Human umbilical cord blood contains abundant immature stem/progenitor cells, which may contribute to the repair of infarcted myocardium. Present study aimed to explore the feasibility and effects of human umbilical cord blood mononuclear cells (HUCBC) transplantation for the treatment of myocardial infarction. METHODS: Forty-five male Wistar rats were randomly divided into three groups: (1) Myocardial infarction (MI plus vehicle, n = 15), (2) MI plus cell transplantation (HUCBC were implanted into the peri-infarct area immediately after MI, n = 15), (3) Normal control group (n = 15). After echocardiography and hemodynamic measurements, the rats were sacrificed for histological and immunochemical examinations one month post MI. RESULTS: The transplanted HUCBC survived and participated the repair process in host heart. Significantly improved left ventricular function was evidenced by echocardiography in cell transplantation group compared to the MI control group. Left ventricular end-diastolic pressure was significantly reduced LVEDP (21.08 +/- 8.10) vs (30.82 +/- 9.59) mm Hg, P < 0.05], +dp/dt(max) [(4.29 +/- 1.27) vs (3.24 +/- 0.75) mm Hg/ms, P < 0.05] and -dp/dt(max) increased [(3.71 +/- 0.79) vs (3.00 +/- 0.49) mm Hg/ms, P < 0.05] in cell transplantation rats compared with MI control rats. vWF immunostaining examination showed significantly increased microvessels within the boundary of infarcted myocardium in cell transplantation group compared to the MI control group (P < 0.01). CONCLUSIONS: HUCBC transplantation may improve cardiac function in MI rats by promoting microvessel formation.

Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction.

BACKGROUND: Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI. METHODS: Forty-five male Wistar rats were randomized into three groups: MI or control group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations. RESULTS: The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P < 0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75) mmHg/ms, P < 0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00 +/- 0.49) mmHg/ms, P < 0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs (11.10 +/- 3.75)%, P < 0.01]. Based on immunostaining of alpha-actin, the numbers of microvessels were significantly (P < 0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/control group. CONCLUSIONS: Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.