Impact of β-blocker selectivity on long-term outcomes in congestive heart failure patients with chronic obstructive pulmonary disease

Yoshiaki Kubota, Kuniya Asai, Erito Furuse, Shunichi Nakamura, Koji Murai, Yayoi Tetsuou Tsukada, Wataru Shimizu Department of Medicine (Division of Cardiology), Nippon Medical School, Bunkyo-ku, Tokyo, Japan Background: Chronic obstructive pulmonary disease (COPD) is present in approximately one-third of all congestive heart failure (CHF) patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration. For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD. In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol. Methods: The study was a retrospective, non-randomized, single center trial. Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34]) and non-β-blocker groups (n=46). The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months. The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol. Results: The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039), and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17–0.99; P=0.047). Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033). In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard ratio: 3.11; 95% confidence interval: 1.47–6.61; P=0.003). Conclusion: These findings support the recommendations to use β-blockers in HF patients with COPD. Importantly, bisoprolol reduced the incidence of CHF and/or COPD exacerbation compared with carvedilol. Keywords: mortality, selective β-blocke

COPD advances in left ventricular diastolic dysfunction

Yoshiaki Kubota,1 Kuniya Asai,1 Koji Murai,1 Yayoi Tetsuou Tsukada,1 Hiroki Hayashi,2 Yoshinobu Saito,2 Arata Azuma,2 Akihiko Gemma,2 Wataru Shimizu1 1Department of Cardiovascular Medicine, 2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Background: COPD is concomitantly present in ~30% of patients with heart failure. Here, we investigated the pulmonary function test parameters for left ventricular (LV) diastolic dysfunction and the relationship between pulmonary function and LV diastolic function in patients with COPD. Patients and methods: Overall, 822 patients who underwent a pulmonary function test and echocardiography simultaneously between January 2011 and December 2012 were evaluated. Finally, 115 patients with COPD and 115 age- and sex-matched control patients with an LV ejection fraction of ≥50% were enrolled. Results: The mean age of the patients was 74.4±10.4 years, and 72.3% were men. No significant differences were found between the two groups regarding comorbidities, such as hypertension, diabetes mellitus, and anemia. The index of LV diastolic function (E/e') and the proportion of patients with high E/e' (defined as E/e' ≥15) were significantly higher in patients with COPD than in control patients (10.5% vs 9.1%, P=0.009; 11.3% vs 4.3%, P=0.046). E/e' was significantly correlated with the residual volume/total lung capacity ratio. Univariate and multivariate analyses revealed severe COPD (Global Initiative for Chronic Obstructive Lung Disease III or IV) to be a significant predictive factor for high E/e' (odds ratio [OR] 5.81, 95% confidence interval [CI] 2.13–15.89, P=0.001 and OR 6.00, 95% CI 2.08–17.35, P=0.001, respectively). Conclusion: Our data suggest that LV diastolic dysfunction as a complication of COPD may be associated with mechanical exclusion of the heart by pulmonary overinflation. Keywords: COPD, heart failure, left ventricular diastolic dysfunctio

Generation of Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells.

Human pluripotent stem cells (PSCs) have the potential to provide a virtually unlimited supply of cells for transplantation therapy. When combined with recent advances in genome editing technologies, human PSCs could offer various approaches that enable gene therapy, drug discovery, disease modeling, and in vitro modeling of human development. De novo generation of hematopoietic stem cells (HSCs) from human PSCs is an important focus in the field, since it enables autologous HSC transplantation to treat many blood disorders and malignancies. Although culture conditions have been established to generate a broad spectrum of hematopoietic progenitors from human PSCs, it remains a significant challenge to generate bona fide HSCs that possess sustained self-renewal and multilineage differentiation capacities upon transplantation. In this review, recent promising advances in the efforts to generate HSCs and hematopoietic progenitors from human PSCs in vitro and in vivo or from somatic cells are discussed