No abstract

In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy. SIRT6-deficient mouse hearts showed hyperactivation of IGF signaling–related genes and their downstream targets. Mechanistically, SIRT6 binds to and suppresses the promoter of IGF signaling–related genes by interacting with c-Jun and deacetylating histone 3 at Lys9 (H3K9). We also found reduced SIRT6 expression in human failing hearts. These findings disclose a new link between SIRT6 and IGF-Akt signaling and implicate SIRT6 in the development of cardiac hypertrophy and failure.

Hospitals have severely curtailed the performance of nonurgent surgical procedures in anticipation of the need to redeploy healthcare resources to meet the projected massive medical needs of patients with coronavirus disease 2019 . Surgical treatment of non-COVID-19 related disease during this period, however, still remains necessary. The decision to proceed with medically necessary, time-sensitive (MeNTS) procedures in the setting of the COVID-19 pandemic requires incorporation of factors (resource limitations, COVID-19 transmission risk to providers and patients) heretofore not overtly considered by surgeons in the already complicated processes of clinical judgment and shared decision-making. We describe a scoring system that systematically integrates these factors to facilitate decision-making and triage for MeNTS procedures, and appropriately weighs individual patient risks with the ethical necessity of optimizing public health concerns. This approach is applicable across a broad range of hospital settings (academic and community, urban and rural) in the midst of the pandemic and may be able to inform case triage as operating room capacity resumes once the acute phase of the pandemic subsides.