Utility of coronary revascularization in patients with ischemic left ventricular dysfunction.

BACKGROUND: Revascularization in patients with left ventricular (LV) dysfunction has been a subject of ongoing uncertainty and conflicting results. This is further complicated by factors including viability, severity of LV dysfunction, and method of revascularization using percutaneous coronary intervention (PCI) versus coronary-artery bypass grafting (CABG). OBJECTIVES: The purpose of this meta-analysis is to evaluate the association of coronary revascularization with outcomes in patients with ischemic LV dysfunction. METHODS: A literature search was conducted for studies reporting on cardiovascular outcomes after revascularization compared to optimal medical therapy (OMT) in patients with ischemic LV dysfunction. RESULTS: A total of 23 studies with 10,110 participants met inclusion criteria. Revascularization was significantly associated with lower all-cause mortality and CV mortality compared to OMT. The association was statistically significant regardless of severity of LV dysfunction or method of revascularization. Subgroup analysis demonstrated that revascularization was significantly associated with lower all-cause and CV mortality compared to OMT for patients with viable myocardium and mixed cohorts with variable viability, but not patients without viable myocardium. Revascularization was not associated with a significant difference in risk of heart failure (HF) hospitalization or acute myocardial infarction (AMI) compared to OMT. CONCLUSIONS: Revascularization in patients with ischemic LV dysfunction is associated with lower risk of all-cause and CV mortality independent of severity of LV dysfunction or method of revascularization. Revascularization is not associated with lower risk of mortality in patients without evidence of viable myocardium and is not associated with lower risk of AMI or HF hospitalization.

Thromboembolism in peripartum cardiomyopathy: a systematic review.

Background: Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of thromboembolic complications in women with PPCM, diagnostic approaches, related outcomes, and effects of therapies that have been used. Methods: English articles were retrieved from Web of Science and PubMed using search terms to capture studies related to PPCM (or postpartum cardiomyopathy) and all combinations of thrombosis- and embolism-related keywords. A total of 347 articles from PubMed and 85 from Web of Science were obtained, and after removing duplicates, 327 articles were screened for original data and classified into four domains: epidemiology, risk factors, diagnosis, and therapy of thromboembolism in PPCM. Ultimately, 30 articles were included. Data were synthesized in summary tables for each domain. Results: Studies in the United States and Europe reported varying incidence for thromboembolism in PPCM, up to 14% in 6 months. Risk factors include elevated levels of coagulation factors, decreased protein C and S activity, decreased fibrinolysis, and a low left ventricular ejection fraction (LVEF). Cesarean delivery and post-operative status were correlated with a higher incidence of thromboembolic complications. Diagnosis relied mostly on ultrasonography and magnetic resonance and depended on the suspected location of thrombus. Anticoagulation has been used mostly for PPCM patients with a reduced LVEF, with the duration varying across guidelines and healthcare systems. Unfractionated heparin and low molecular weight heparin (LMWH) were considered safe choices during pregnancy, while warfarin and novel oral anticoagulants (NOACs) were used postpartum. The association of bromocriptine with risk of thromboembolic complications remains debated. Conclusions: There are important gaps in our understanding of the epidemiology, risk stratification, and optimal secondary prevention of thromboembolism in PPCM. Larger prospective studies with detailed phenotyping are required.

Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.

Both the induction of SPARC expression and the loss of the p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival. This study determined whether the loss of Sparc in astrocytes that are null for p53 would result in reduced cell survival and tumor formation and increased tumor immunogenicity in an in vivo xenograft brain tumor model. In vitro, the loss of Sparc in p53-null astrocytes resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7 days after intracranial implantation, Sparc-null tumors had decreased tumor cell survival, proliferation and reduced tumor size. The loss of Sparc promoted microglia/macrophage activation and phagocytosis of tumor cells. Our results indicate that the loss of p53 by deletion/mutation in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance.