Laminin-221 Enhances Therapeutic Effects of Human-Induced Pluripotent Stem Cell-Derived 3-Dimensional Engineered Cardiac Tissue Transplantation in a Rat Ischemic Cardiomyopathy Model.

Background Extracellular matrix, especially laminin-221, may play crucial roles in viability and survival of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) after in vivo transplant. Then, we hypothesized laminin-221 may have an adjuvant effect on therapeutic efficacy by enhancing cell viability and survival after transplantation of 3-dimensional engineered cardiac tissue (ECT) to a rat model of myocardial infarction. Methods and Results In vitro study indicates the impacts of laminin-221 on hiPS-CMs were analyzed on the basis of mechanical function, mitochondrial function, and tolerance to hypoxia. We constructed 3-dimensional ECT containing hiPS-CMs and fibrin gel conjugated with laminin-221. Heart function and in vivo behavior were assessed after engraftment of 3-dimensional ECT (laminin-conjugated ECT, n=10; ECT, n=10; control, n=10) in a rat model of myocardial infarction. In vitro assessment indicated that laminin-221 improves systolic velocity, diastolic velocity, and maximum capacity of oxidative metabolism of hiPS-CMs. Cell viability and lactate dehydrogenase production revealed that laminin-221 improved tolerance to hypoxia. Furthermore, analysis of mRNA expression revealed that antiapoptotic genes were upregulated in the laminin group under hypoxic conditions. Left ventricular ejection fraction of the laminin-conjugated ECT group was significantly better than that of other groups 4 weeks after transplantation. Laminin-conjugated ECT transplantation was associated with significant improvements in expression levels of rat vascular endothelial growth factor. In early assessments, cell survival was also improved in laminin-conjugated ECTs compared with ECT transplantation without laminin-221. Conclusions In vitro laminin-221 enhanced mechanical and metabolic function of hiPS-CMs and improved the therapeutic impact of 3-dimensional ECT in a rat ischemic cardiomyopathy model. These findings suggest that adjuvant laminin-221 may provide a clinical benefit to hiPS-CM constructs.

Surgical Results for Infective Endocarditis Complicated With Cardiogenic Shock.

BACKGROUND: Infective endocarditis remains associated with substantial mortality and morbidity rates, and the presence of acute heart failure (AHF) compromises clinical results after valve surgery; however, little is known in cardiogenic shock (CGS) patients. This study evaluated the clinical results and risk of mortality in CGS patients after valve surgery.Methods and Results:This study enrolled 585 patients who underwent valve surgery for active endocarditis at 14 institutions between 2009 and 2017. Of these patients, 69 (12%) were in CGS, which was defined as systolic blood pressure <80 mmHg and severe pulmonary congestion, requiring mechanical ventilation and/or mechanical circulatory support, preoperatively. The predictors of CGS were analyzed, and clinical results of patients with non-CGS AHF (n=215) were evaluated and compared.Staphylococcus aureusinfection (odds ratio [OR] 2.19; P=0.044), double valve involvement (OR 3.37; P=0.003), and larger vegetation (OR 1.05; P=0.036) were risk factors for CGS. Hospital mortality occurred in 27 (13%) non-CGS AHF patients and in 15 (22%) CGS patients (P=0.079). Overall survival at 1 and 5 years in CGS patients was 76% and 69%, respectively, and there were no significant differences in overall survival compared with non-CGS AHF patients (P=1.000). CONCLUSIONS: Clinical results after valve surgery in CGS patients remain challenging; however, mid-term results were equivalent to those of non-CGS AHF patients.

Results of surgical management of infective endocarditis associated with Staphylococcus aureus.

OBJECTIVES: Staphylococcus aureus (SA) is a leading cause of infective endocarditis (IE), and such cases are on the rise. Our objective was to evaluate the clinical outcomes of surgical intervention in patients with SA-associated IE and to identify the factors associated with outcomes. METHODS: Between 2009 and 2017, 585 patients underwent valve surgery for definitive left-sided IE at 14 affiliated hospitals. Their medical records were retrospectively reviewed, and the preoperative variables and clinical results of patients with (n = 117) or without SA infection (n = 468) were compared. RESULTS: The SA group had a more critical preoperative condition with higher rates of chronic haemodialysis, preoperative embolic events and preoperative inflammation levels, as well as worse renal function. In-hospital mortality was 20% and 7% in the patients with or without SA infection, respectively. The overall survival rate at 1 year and 5 years was 72% and 62% in the SA group, and 88% and 81% in the non-SA group, respectively (P < 0.001). The Cox hazard analysis revealed that methicillin-resistant SA infection was an independent risk factor for overall mortality in the SA group. The rate of freedom from recurrence of endocarditis at 1 year and 5 years was 95% and 90% in the SA group and 96% and 92% in the non-SA group, respectively (P = 0.43). CONCLUSIONS: The short- and mid-term outcomes after valve surgery for active IE in patients with SA are still challenging. Methicillin-resistant SA infection is an independent predictor of mid-term mortality.

Diabetes mellitus adversely affects mortality and recurrence after valve surgery for infective endocarditis.

BACKGROUND: Although diabetes mellitus (DM) increases the incidence of infective endocarditis (IE), little is known about the outcome of valve surgery for active IE in patients with DM. We evaluated the clinical outcomes of valve surgery for IE in patients with DM. METHODS: Between 2009 and 2016, 470 patients underwent valve surgery for definitive left-sided active IE at 12 affiliated hospitals. We compared the preoperative variables and clinical outcomes between patients without (n = 374) and with DM (n = 96). RESULTS: Staphylococcus and chronic hemodialysis were more prevalent in patients with DM, and these patients had greater preoperative inflammation levels and worse renal function than patients without DM. In-hospital mortality was 8% in patients without DM and 13% in patients with DM (P = .187). The overall survival rate at 1 and 5 years was 87% and 81% in patients without DM and 72% and 59% in patients with DM (P < .001). The incidence of infection-related death was greater in patients with DM than in patients without DM (P < .001; hazard ratio 3.74 [1.78-7.71]). Freedom from the recurrence of endocarditis at 1 and 5 years postoperatively was 98% and 95% in patients without DM, and 89% and 78% in patients with DM (P < .001), respectively. The Cox hazard analysis revealed that the presence of DM was the only independent risk for recurrence (hazard ratio 3.74 [1.45-9.54], P = .007). CONCLUSIONS: The short- and mid-term outcome after valve surgery for active IE in patients with DM is worse because of the greater prevalence of infection-related death and IE recurrence.

Recent Surgical Results for Active Endocarditis Complicated With Perivalvular Abscess.

BACKGROUND: Surgical treatment for endocarditis patients with a perivalvular abscess is still challenging.Methods and Results:From 2009 to 2016, 470 patients underwent surgery for active endocarditis at 11 hospitals. Of these, 226 patients underwent aortic valve surgery. We compared the clinical results of 162 patients without a perivalvular abscess, 37 patients who required patch reconstruction of the aortic annulus (PR group) and 27 who underwent aortic root replacement (ARR group). Patients with a perivalvular abscess had a greater number ofStaphylococcusspecies and prosthetic valve endocarditis, a greater level of inflammation at diagnosis and symptomatic heart failure before surgery, especially in the ARR group. Nevertheless, the duration between diagnosis and surgery was similar, because of a high prevalence of intracranial hemorrhage in the ARR group. Hospital death occurred in 13 (9%) patients without a perivalvular abscess, in 4 (12%) in the PR and in 7 (32%) in the ARR group. Postoperative inflammation and end-organ function were similar between the groups. Overall survival of patients without a perivalvular abscess and that of the PR group was similar, but was significantly worse in the ARR group (P=0.050, 0.026). Freedom from endocarditis recurrence was similar among all patients. CONCLUSIONS: Patients treated with patch reconstruction showed favorable clinical results. Early surgical intervention is necessary when a refractory invasive infection is suspected.