Chengheng Hu

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

AbstractIn 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 I2 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.

Thermodilution-Derived Coronary Microvascular Resistance and Flow Reserve in Patients With Cardiac Syndrome X

Background—Although increased coronary microvascular resistance (CMR), resulting in coronary microvascular dysfunction, is speculated to be responsible for myocardial ischemia in patients with cardiac syndrome X (CSX), it has never been directly demonstrated, and the correlation between CMR and severity of myocardial ischemia has not been elucidated in this setting. This study aimed to ascertain the increased CMR directly and to explore the relationship between CMR and severity of ischemia in patients with CSX. Methods and Results—We studied 18 patients with CSX and 18 age- and sex-matched control subjects. Thermodilution-derived coronary flow reserve and index of microvascular resistance were measured using a pressure–temperature sensor-tipped coronary wire. Exercise treadmill test was performed by the Bruce protocol for calculating Duke treadmill score. Coronary flow reserve was significantly lower (2.37±0.81 versus 3.68±0.72; P<0.001) and index of microvascular resistance was higher (33.1±7.9 versus 18.8±5.6 U; P<0.001) in patients with CSX compared with those in control subjects. The Duke treadmill score was correlated positively to coronary flow reserve (r=0.539; P=0.021) and negatively to index of microvascular resistance (r=−0.742; P<0.001) in patients with CSX. Conclusions—Using an intracoronary thermodilution method, we for the first time directly demonstrated an increased microvascular resistance in patients with CSX. Furthermore, severity of ischemia was found to be intimately associated with CMR in this setting.

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.

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.

Islet‐1 Overexpression in Human Mesenchymal Stem Cells Promotes Vascularization Through Monocyte Chemoattractant Protein‐3

The LIM‐homeobox transcription factor islet‐1 (ISL1) has been proposed to mark a cardiovascular progenitor cell lineage that gives rise to cardiomyocytes, endothelial cells, and smooth muscle cells. The aim of this study was to investigate whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) influenced the differentiation capacity and angiogenic properties of hMSCs. The lentiviral vector, EF1α‐ISL1, was constructed using the Multisite Gateway System and used to transduce hMSCs. We found that ISL1 overexpression did not alter the proliferation, migration, or survival of hMSCs or affect their ability to differentiate into osteoblasts, adipocytes, cardiomyocytes, or endotheliocytes. However, ISL1‐hMSCs differentiated into smooth muscle cells more efficiently than control hMSCs. Furthermore, conditioned medium from ISL1‐hMSCs greatly enhanced the survival, migration, and tube‐formation ability of human umbilical vein endothelial cells (HUVECs) in vitro. In vivo angiogenesis assays also showed much more vascular‐like structures in the group cotransplanted with ISL1‐hMSCs and HUVECs than in the group cotransplanted with control hMSCs and HUVECs. Quantitative RT‐PCR and antibody arrays detected monocyte chemoattractant protein‐3 (MCP3) at a higher level in conditioned medium from ISL1‐hMSCs cultures than in conditioned medium from control hMSCs. Neutralization assays showed that addition of an anti‐MCP3 antibody to ISL1‐hMSCs‐conditioned medium efficiently abolished the angiogenesis‐promoting effect of ISL1‐hMSCs. Our data suggest that overexpression of ISL1 in hMSCs promotes angiogenesis in vitro and in vivo through increasing secretion of paracrine factors, smooth muscle differentiation ability, and enhancing the survival of HUVECs. Stem Cells 2014;32:1843–1854

Documentation of impaired coronary blood flow by TIMI frame count method in patients with atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is associated with impaired coronary flow and diminished myocardial perfusion. In the present study we aimed to evaluate coronary blood flow by means of Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) in patients with AF in the absence of obstructive coronary artery disease (CAD). METHODS This prospective study initially enrolled 166 patients with AF and 332 age- and gender-matched control subjects without AF. After diagnostic coronary angiography, TFC was assessed in the participants without obstructive CAD, with 146 in the AF group and 150 in the control group. RESULTS The TFC for three major coronary arteries and the mean TFC were found to be significantly higher in AF patients compared to control subjects (34.1 ± 10.4 vs. 25.0 ± 10.4, 31.8 ± 9.7 vs. 23.7 ± 9.1, and 32.3 ± 9.5 vs. 24.1 ± 8.4 for each artery and 32.8 ± 9.2 vs. 24.3 ± 8.9 for mean TFC, p<0.001 for all comparisons). The mean TFC was 28.8 ± 7.9 in patients with paroxysmal AF, 33.7 ± 8.7 in those with persistent AF, and 39.0 ± 8.8 in those with long-standing or permanent AF (p<0.01 for all comparisons). After multivariate analysis, we found that the presence of AF remains to be independently associated with mean TFC. In AF group, baseline heart rate, left ventricular ejection fraction, AF duration and left atrium diameter were found to be independently associated with mean TFC. CONCLUSIONS Patients with atrial fibrillation in the absence of obstructive coronary artery disease have significantly higher TIMI frame counts for all three coronary vessels, indicating impaired coronary blood flow, compared to the control subjects without atrial fibrillation.

Short-term effects of enhanced external counterpulsation on transthoracic coronary flow velocity and reserve in patients with coronary slow flow ☆

flow velocity and reserve in patients with coronary slow flow☆ Chufan Luo , Donghong Liu , Zhimin Du , Gregory W. Barsness , Xing Wu , Chengheng Hu , Yi Li , Xun Hu , Yan Zhang , Guifu Wu a,d,⁎ a Division of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China b Department of Ultrasound, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China c Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn 55905, USA d Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China

Effect of enhanced external counterpulsation on coronary slow flow and its relation with endothelial function and inflammation: a mid-term follow-up study.

Background: Although enhanced external counterpulsation (EECP) showed short-term effects in improving coronary flow in patients with coronary slow flow (CSF), whether such improvement is durable remains uncertain, and the relationships between such improvement and changes in endothelial function as well as inflammatory markers have not been elucidated. Objectives: The aim of the present study was to investigate the effects of EECP on transthoracic coronary flow, flow-mediated dilatation (FMD), and high-sensitivity C-reactive protein (hsCRP) in patients with CSF. Methods: Forty-five patients with documented CSF underwent transthoracic Doppler echocardiography (TTDE) for the assessment of coronary diastolic peak flow velocity (DPFV) and coronary flow reserve (CFR), and measurements of FMD and hsCRP; they were then nonrandomly assigned to two groups. Subjects in the control group (n = 24) received only medical therapy, and those in the EECP group (n = 21) were additionally treated with the 36 one-hour sessions of EECP. After 8 weeks of medical/EECP therapy, TTDE, FMD, and hsCRP examinations were repeated, and TTDE was additionally repeated after the 6-month clinical follow-up. Results: In the EECP group, resting DPFV, hyperemic DPFV, and CFR were significantly increased shortly after therapy (p < 0.001) and the improvement was maintained up to the 6-month follow-up, whereas in the control group those variables were not statistically increased. Meanwhile, hsCRP significantly decreased and FMD increased after therapy in the EECP group (p < 0.001). In all subjects, CFR improvement was negatively correlated with hsCRP change and positively correlated with FMD increase (p < 0.001). Conclusions: EECP may have a durable effect in improving coronary flow in patients with CSF. Such improvement is related to the favorable effects of EECP on vascular inflammation and endothelial function.

GW24-e1282 A noninvasive sizing method to choose fitted atrial septal defect occluder by transthoracic echocardiography in adults with secundum atrial septal defects

Objectives In our clinical practice, we try to find a feasible method to size the hole of ASD by only 2D transthoracic echocardiography (2D-TTE). It should be more practical, less expensive and without pain. Methods Sixty-seven consecutive adult patients (26 males, 41 females, mean age 38.4 ± 8.5 years) were scheduled to have ASD device closure. Before that, we calculated the size of ASD by 2D transthoracic echocardiography (2D-TTE) through parasternal four chambers view, parasternal short axes view, apical four chambers view, subcostal four chambers view and subcostal two chambers view. The biggest size from the views would be chosen for ASD device closure. Meanwhile, we paid attention to the ASD margins, and we divided them to floppy margin group (n = 24) and firm margin group (n = 43). For the floppy margin patients, we would add 2 or 4 mm more than the 2D-TTE size for preparing ASD device size. And for the firm margin patient, we chose the same 2D-TTE size for ASD device size. Results The total successful ASD device closure rate was 94.0% (63/67). The average total trans-catheter ASD closure time was 42.3 ± 12.5 minutes. ASD device closure succeeded at the first time was: 40/43 (93.0%) in the firm margin group; 16/24 (66.7%) in the floppy margin group. For the rest patient whose ASD couldn’t be closed at the first time, we reduced the size 2–5 mm in the firm margin group, the rest 3 all got successful ASD device closed. As in the floppy margin group, there were 4 patients needed adding 4–6 mm to the 2D-TTE size and then their ASD device closed successfully. There were only 4 patients (6%) in floppy margin group couldn’t be ASD device closed. For average 1.4 years follow up, only 6 patients (9.5%) had some chest pain complain, but all the devices were stable. Conclusions With our experience, the sizing based on 2D-TTE could be used for ASD device selection. The multiple views of TTE should be used to calculate the biggest size of ASD. And the margins of the ASD hole also need to be considered.

e0114 Expression of pregnancy-association plasma protein A and inducible nitric oxide synthase in the wall of balloon injured and early atherosclerotic porcine coronary artery

Purpose To investigate the role of pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in the progress of injured-restenosis and atherosclerosis, and the relationship between the expression of PAPP-A and inducible nitric oxide synthase (iNOS) in the wall of coronary artery. Methods The balloon injury procedure was done in the coronary arteries of 5 male pigs (injury group), and the artery segments were harvested in 28d after balloon injury. The expression of PAPP-A and iNOS were detected in the wall of coronary arteries by the means of immunohistochemical study and reverse transcription-polymerase chain raction. Expression of PAPP-A and iNOS were also detected in coronary artery wall of four pigs fed a high-cholesterol atherogenic diet for 15 weeks (CHOL group). Results A marked increase in PAPP-A-positive cell number of the injury group was seen compared with the CHOL group, both in medial smooth muscle cells (PAPP-A staining: 33.2±2.9 vs 5.5±2.8, p<0.05) and neointimal (intimal) cells (PAPP-A staining: 28.3±3.1 vs 3.8±2.4, p<0.05); while iNOS-positive cell number decrease, only in neointimal (intimal) cells (iNOS stain: 1.1±0.3 vs 18.4±4.2, p<0.01). The expression of PAPP-A mRNA was higher in the injury group, compared with the CHOL group (0.81±0.08 vs 0.54±0.13, p<0.05), but nearly no expression in “normal” control vessel segements (0.03±0.01); while iNOS mRNA was lower in the injury group (0.18±0.09 vs 0.62±0.13, p<0.05). Conclusion PAPP-A plays role in the progress of early atherosclerotic lesions and restenostic lesions.