Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies are employing a range of stem cell varieties. These stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity for unlimited proliferation and differentiation into cardiomyocytes, are a promising cell source for myocardial regeneration therapy. In this review, we discuss the following topics: (1) what are iPSCs; (2) the limitations and solutions for the translation of iPSC-CMs practically; and (3) the current therapeutic clinical trials.

Comparative outcomes of lung volume reduction surgery and lung transplantation: a systematic review and meta-analysis.

Background: Lung volume reduction (LVR) and lung transplantation (LTx) have been used in different populations of chronic obstructive pulmonary disease (COPD) patients. To date, comparative study of LVR and LTx has not been performed. We sought to address this gap by pooling the existing evidence in the literature. Methods: An electronic search was performed to identify all prospective studies on LVR and LTx published since 2000. Baseline characteristics, perioperative variables, and clinical outcomes were extracted and pooled for meta-analysis. Results: The analysis included 65 prospective studies comprising 3,671 patients [LTx: 15 studies (n=1,445), LVR: 50 studies (n=2,226)]. Mean age was 60 [95% confidence interval (CI): 58-62] years and comparable between the two groups. Females were 51% (95% CI: 30-71%) in the LTx group vs. 28% (95% CI: 21-36%) in LVR group (P=0.05). Baseline 6-minute walk test (6MWT) and pulmonary function tests were comparable except for the forced expiratory volume in 1 second (FEV1), which was lower in the LTx group [21.8% (95% CI: 16.8-26.7%) vs. 27.3% (95% CI: 25.5-29.2%), P=0.04]. Postoperatively, both groups experienced improved FEV1, however post-LTx FEV1 was significantly higher than post-LVR FEV1 [54.9% (95% CI: 41.4-68.4%) vs. 32.5% (95% CI: 30.1-34.8%), P<0.01]. 6MWT was also improved after both procedures [LTx: 212.9 (95% CI: 119.0-306.9) to 454.4 m (95% CI: 334.7-574.2), P<0.01; LVR: 286 (95% CI: 270.2-301.9) to 409.1 m (95% CI: 392.1-426.0), P<0.01], however, with no significant difference between the groups. Pooled survival over time showed no significant difference between the groups. Conclusions: LTx results in better FEV1 but otherwise has comparable outcomes to LVR.

Surgical ventricular reconstruction for ischemic cardiomyopathy-a systematic review and meta-analysis of 7,685 patients.

Background: Surgical ventricular reconstruction (SVR) has been used to control adverse ventricular remodeling and improve cardiac function in ischemic cardiomyopathy. The purpose of this systematic review and meta-analysis was to collect and analyze all available evidence on the utilization and efficacy of SVR. Methods: An electronic database search was performed to identify all retrospective and prospective studies on SVR for ischemic cardiomyopathy in the English literature from 2000 through 2020. A total of 92 articles with a collective 7,685 patients undergoing SVR were included in the final analysis. Results: The mean patient age was 61 years (95% CI: 59-63) and 80% (78-82%) were male. Congestive heart failure was present in 66% (54-78%) and angina in 58% (45-70%). Concomitant coronary artery bypass grafting was undertaken in 92% (90-93%) while 21% (18-24%) underwent mitral valve repair. Pre vs. post-SVR, significant improvement was seen in left ventricular ejection fraction (LVEF) [29.9% (28.8-31.2%) vs. 40.9% (39.4-42.4%), P<0.01], left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD) [LVESD: 49.9 mm (48.1-51.7) vs. 45 mm (42.8-47.3), P<0.01, LVEDD: 63.8 mm (62-65.6) vs. 58.23 mm (56.6-60), P<0.01], and left ventricular end-systolic (LVESVI) and end-diastolic volume indices (LVEDVI) [LVESVI: 83.9 mL/m2 (79.3-88.4) vs. 46.8 mL/m2 (43.5-50.1), P<0.01; LVEDVI: 119.9 mL/m2 (112.1-127.6) vs. 79.6 mL/m2 (73.6-85.7), P<0.01]. Mean New York Heart Association class improved from 3 (2.8-3.1) to 1.8 (1.5-2) (P<0.01). The 30-day mortality was 4% (3-5%) while late mortality was 19% (9-34%) at a mean follow-up of 27.5 [21-34] months. Conclusions: In patients with ischemic cardiomyopathy, SVR reduces left ventricular volumes and improves systolic function leading to symptomatic improvement.