Chin-Chang Cheng

Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs) and iPSC-conditioned medium (iPSC CM) were explored in monocrotaline (MCT)-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1β, IL-6, IL-12α, IL-12β, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation.

The effect of failure mode and effect analysis on reducing percutaneous coronary intervention hospital door-to-balloon time and mortality in ST segment elevation myocardial infarction

Background Door-to-balloon (D2B) time is an important factor in the outcome of ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. We aimed to use failure mode and effect analysis to reduce the D2B time for patients with STEMI and to improve clinical outcomes. Methods There were three stages in this study. In Stage 0, data collected from 2005–2006 was used to identify failures in the process, and during Stage 2 (2007) and Stage 3 (2008) the efficacy of intrahospital and interhospital strategies to reduce the D2B time were evaluated. This study enrolled 385 patients; 86 from 2005–2006; 80 in 2007; and 219 in 2008. Results By making improvements in these steps, the median D2B time was reduced from 146 min to 32 min for all patients. The proportion of patients with a D2B time of <90 min significantly increased from Stage 0 to Stage 1 and from Stage 1 to Stage 2, for all patients as well as for the non-transferred and transferred subgroups of patients (all p values <0.0001). For non-transferred patients, only reinfarction-free survival showed significant difference among the three stages (p=0.0225), and for transferred patients, only overall survival showed significant difference among the three stages (p=0.0322). Coxs proportional hazards regression analysis showed Stage 2 was associated with a lower risk of reinfarction and mortality compared with Stage 0. Conclusions This study found that failure mode and effect analysis is a powerful method for identifying weaknesses in D2B processes and evaluating strategies to reduce the D2B time.

Tricuspid flow propagation velocity predicts exercise tolerance and readmission in patients with systemic lupus erythematosus.

BACKGROUND Evaluating right ventricular dysfunction, pulmonary artery systolic pressure (PASP), and exercise tolerance is critical in patients with systemic lupus erythematosus (SLE) because of the high mortality rate in such patients with pulmonary arterial hypertension (PAH). The aim of this study was to use the flow propagation velocity (FPV) of early diastolic tricuspid inflow to evaluate exercise tolerance and PAH severity and to predict readmission in patients with SLE. METHODS A total of 66 patients with SLE with or without PAH and 30 healthy control subjects were enrolled. Controls were age-matched to patients with SLE and without PAH. All patients completed the 6-minute walking distance (6MWD) test and underwent standard echocardiography. Tricuspid FPV was measured in the modified parasternal short-axis view using the color M-mode technique. PAH was defined as PASP > 35 mm Hg using the tricuspid regurgitant method. RESULTS Patients with SLE and PAH had significantly lower tricuspid FPVs and 6MWDs than patients in the other 2 groups (both P values < .001). Tricuspid FPV was well correlated with 6MWD (r = 0.748, P < .001). In multivariate analysis, right atrial pressure was the only independent factor affecting tricuspid FPV (R(2) = 0.394, P < .001), and 6MWD was affected only by tricuspid FPV and PASP (R(2) = 0.629, P < .001). Patients with SLE who had been readmitted had lower tricuspid FPVs than those who had not (P = .035). Furthermore, FPV > or = 35.4 cm/s predicted 6MWD > or = 350 m and a lower 1-year readmission rate with good sensitivity and specificity. CONCLUSION The tricuspid FPV technique provides a simple method for predicting exercise tolerance, the severity of PAH, and readmission among patients with SLE.

Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction: A Nationwide Study

Abstract Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database. This was a nationwide, propensity score-matched case–control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI). Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08–2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status. Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status.

Hypertensive disorders of pregnancy and future heart failure risk: A nationwide population-based retrospective cohort study

OBJECTIVE To assess whether hypertensive disorders of pregnancy (HDP) increased the risk of subsequent heart failure (HF) and identify possible risk factors. STUDY DESIGN A nationwide population-based retrospective cohort study. MAIN OUTCOME MEASURES Incidence of heart failure. RESULTS Among the 23.3 million individuals registered in the National Health Insurance Research Database in Taiwan, 29,186 patients with HDP and 116,744 matched controls were identified. The overall incidence of HF was greater in the HDP group than it was in the control group (9.83 vs. 1.67 per 10,000 person-years), with a significant incidence rate ratio (IRR = 5.88, 95% confidence interval [CI] 5.84-5.92, p < 0.0001). When stratified by age, parity, gestational age, gestational number, and follow-up years, the IRR for subsequent HF remained significantly higher in the HDP group in all stratifications. Additionally, the Kaplan-Meier analysis indicated that the cumulative incidence rate of HF was higher in the HDP group than it was in the control group. The Cox proportional-hazard model analysis showed that in addition to HDP, single parity, preterm and hypertension were independent risk factors for developing HF. Moreover, HF was more likely to develop within 5 years post-partum. Among patients with a history of HDP, the Cox proportional-hazard model showed that severe forms of HDP and increased HDP occurrences were independently associated with the subsequent development of HF. CONCLUSIONS Patients who have experienced HDP presented an increased risk for developing HF later in life. Moreover, among individuals with a history of HDP, those with severe forms of HDP or recurrent HDP displayed an increased subsequent risk of HF.

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective β-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective β1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the β2-adrenoceptor.

An Analysis of Emergency Department Visits and the Survival Rate for Colorectal Cancer Patients: A Nationwide Population-based Study

Objective We examined the general characteristics, survival rate, and most common reasons for visiting the emergency department (ED) among colorectal cancer patients in Taiwan. We performed a population-based retrospective study and used data sourced from the National Health Insurance Research Database (NHIRD). Methods The colorectal cancer patient population, their diagnosis, and their medical management at the ED were identified using the Longitudinal Health Insurance Database 2000 (HV) codes and International Classification of Diseases, Ninth Revision, Clinical Modification system. We investigated their reasons for visiting the ED and the medications used there, analyzed their cumulative survival curves using the Kaplan-Meier method, and compared the survival curves with other colorectal cancer patients who had never visited the ED. Results Between 2000 and 2012, there were 6,532 ED visits by 3,347 colorectal patients, and the number per year increased gradually. The top three most common reasons for visiting ED were ill-defined conditions, abdominal pain, and intestinal obstruction. The overall survival rates of colorectal patients in the ED visit group at 3, 5, and 10 years, were 0.65, 0.56, and 0.47, respectively, without significant differences from the rates among colorectal cancer patients who did not visit the ED (p=0.2072). Conclusion We described the circumstances of ED visitation by colorectal cancer patients in Taiwan. Health care providers and researchers should pay more attention to improve medical care quality and investigate more details to predict the outcome among colorectal cancer patients.

Ankylosing spondylitis associated with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a frequent complication of connective tissue diseases, such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. However, the occurrence of PAH in a patient with ankylosing spondylitis (AS) has not been previously reported with a detailed clinical description in the English literature. We herein report the first case of AS associated PAH in a 27-year-old Taiwanese man with a chief complaint of intermittent palpitations lasting for two years. To the best of our knowledge, this is the first reported case of AS associated with PAH with a detailed clinical description and findings of right heart catheterization published in the English literature.

TCT-186 Comparison of 5-year outcomes between drug-eluting and bare-metal stents in patients after acute myocardial infarction with or without diabetes

Masahiro Natsuaki, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Masashi Iwabuchi, Takeshi Kimura Saiseikai Fukuoka General Hospital, Fukuoka, Japan, Kinki University, Sayama, Japan, Kobe City Medical Center General Hospital, Kobe, Japan, Tenri Hospital, Tenri, Japan, Kurashiki Central Hospital -Okayama -Japan, Kurashiki, Japan, Kokura Memorial Hospital, Kitakyushu, Japan, Kyoto University, Kyoto, Japan

Angiopoietin-1 and Endoglin Are Not Associated with Pulmonary Arterial Hypertension in Patients with Systemic Lupus Erythematous

Objective: Angiopoietin (Ang)-1, an angiogenic factor, has been demonstrated to regulate pathologic smooth muscle cell hyperplasia. Endoglin (Eng) plays a role in cardiovascular development, vascular remodeling and active angiogenesis. Both were reported to be associated with the development of pulmonary artery hypertension (PAH) in scleroderma. Therefore, we hypothesized that serum levels of Ang-1 and Eng would be associated with PAH in patients with systemic lupus erythematous (SLE). Methods: Serum Ang-1 and Eng levels were measured by enzyme-linked immunoassay in 22 SLE patients with PAH, 80 patients without PAH and 16 healthy controls, and were correlated with disease activities. Results: Ang-1 levels were significantly lower in SLE patients (19.37±8.02 ng/mL) compared with healthy controls (32.00±9.89 ng/mL, p＜0.001). Among SLE patients, Ang-1 levels were lower in patients without PAH (18.75±7.90 ng/mL) compared with those with PAH (21.60±8.24 ng/mL, p=0.394). However, the difference did not reach a statistical significance. There was no difference of Eng levels between SLE patients (4.62±1.60 ng/mL) and healthy controls (4.78±0.99 ng/mL, p=0.400) and between SLE patients without PAH (4.69±1.69 ng/mL) and with PAH (4.37±1.20 ng/mL, p=0.441). In addition, Ang-1 and Eng levels did not correlate with C3, C4 and anti-dsDNA Ab in patients with SLE. Conclusion: Serum Ang-1 and Eng levels were not good biomarkers in predicting PAH in patients with SLE.