Efficacy of Primary Surgical Versus Medical Intervention for Treatment of Left-Sided Infective Endocarditis.

BACKGROUND: Left-sided staphylococcal, streptococcal, and enterococcal infective endocarditis (IE) is associated with poor clinical outcomes. Our primary aim is to compare clinical outcomes of staphylococcal, streptococcal, and enterococcal IE patients who undergo valve replacement surgery and outcomes of patients who are treated solely with antibiotics. METHODS: All patients were treated medically or surgically for left-sided staphylococcal, streptococcal, or enterococcal IE at our institution from 1998 to 2014 and were retrospectively studied. The primary outcome of interest was 30-day and 1-year mortality, and secondary outcomes included posttreatment septic shock, embolic events, stroke, and end-stage renal disease at 30 days. Inverse probability treatment weights, derived from propensity scores, were used to balance the medical and surgical cohorts across clinical risk factors, The Society of Thoracic Surgeon scores, and pathogens. Outcomes were compared comprehensively and in a staphylococcal-only subanalysis. RESULTS: Study population consisted of 245 surgical patients and 164 medical patients. Mortality at 30 days was higher in the medical cohort, both in aggregate and for staphylococcal only (all, 7% vs 16%, P < .001; staphylococcal only, 7% vs 22%, P < .001). Surgical patients had a higher incidence of septic shock and renal dysfunction; however, stroke and embolic events at 30 days were not different between cohorts. Cox survival analysis demonstrated that surgical treatment provided a 1-year survival benefit, with a hazard ratio of 0.48 (95% confidence interval, 0.36 to 0.64) that was robust regardless of pathogen. CONCLUSIONS: Compared with medical management, valve replacement surgery in patients with left-sided staphylococcal, streptococcal, or enterococcal IE appears to confer a survival advantage at 30 days and 1 year.

Activin type II receptor ligand signaling inhibition after experimental ischemic heart failure attenuates cardiac remodeling and prevents fibrosis.

Myostatin (MSTN) is a transforming growth factor (TGF)-ß superfamily member that acts as a negative regulator of muscle growth and may play a role in cardiac remodeling. We hypothesized that inhibition of activin type II receptors (ACTRII) to reduce MSTN signaling would reduce pathological cardiac remodeling in experimental heart failure (HF). C57BL/6J mice underwent left anterior descending coronary artery ligation under anesthesia to induce myocardial infarction (MI) or no ligation (sham). MI and sham animals were each randomly divided into groups (n ≥ 10 mice/group) receiving an ACTRII or ACTRII/TGFß receptor-signaling inhibiting strategy: 1) myo-Fc group (weekly 10 mg/kg Myo-Fc) or 2) Fol + TGFi group (daily 12 µg/kg follistatin plus 2 mg/kg TGFß receptor inhibitor), versus controls. ACTRII/TGFBR signaling inhibition preserved cardiac function by echocardiography and prevented an increase in brain natriuretic peptide (BNP). ACTRII/TGFBR inhibition resulted in increased phosphorylation (P) of Akt and decreased P-p38 mitogen-activated protein kinase (MAPK) in MI mice. In vitro, Akt contributed to P-SMAD2,3, P-p38, and BNP regulation in cardiomyocytes. ACTRII/TGFBR inhibition increased sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) levels and decreased unfolded protein response (UPR) markers in MI mice. ACTRII/TGFBR inhibition was associated with a decrease in cardiac fibrosis and fibrosis markers, connective tissue growth factor (CTGF), type I collagen, fibronectin, α-smooth muscle actin, and matrix metalloproteinase (MMP)-12 in MI mice. MSTN exerted a direct regulation on the UPR marker eukaryotic translation initiation factor-2α (eIf2α) in cardiomyocytes. Our study suggests that ACTRII ligand inhibition has beneficial effects on cardiac signaling and fibrosis after ischemic HF.NEW & NOTEWORTHY Activin type II receptor ligand inhibition resulted in preserved cardiac function, a decrease in cardiac fibrosis, improved SERCA2a levels, and a prevention of the unfolded protein response in mice with myocardial infarction.