Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

M itral-aortic intervalvular fibrosa (MAIVF) is the fibrous tissue establishing continuity between anterior mitral leaflet and noncoronary cusp of aortic valve. Because MAIVF is avascular and thin, it may be more prone to injury and infection. MAIVF pseudoaneurysm (MAIVF-P) is a rare complication of infective endocarditis or aortic valve surgery.In May 2015, a 66-year-old male smoker with diabetes mellitus had fever and chills, he responded to empiric antimicrobial treatment. One month later, he had heart failure. Mitral-aortic endocarditis was diagnosed, and double valve replacement done with bioprostheses. Positron emission tomography-computed tomography imaging showed L4-L5 hyperfixation and inflammatory spondylodiscitis. In September 2015, he underwent L3-S1 surgery. In this instance, transthoracic echocardiography (TTE) diagnosed an aortic periprosthetic leak and moderate regurgitation.In Figure 1, three-dimensional echocardiography shows a large aortic periprosthetic abscess in MAIVF. Fistulation occurred in both atria. There is an unexpected systolic compression and narrowing of the left main (LM) trunk, also observed at coronary angiography. White arrow indicates LM trunk systolic narrowing (MV ¼ mitral valve).At surgery, we found a 2.5 Â 1.3-cm MAIVF-P communicating with both atria; infected tissues and previous implanted prostheses were removed and replaced. The postoperative course was uneventful, and TTE showed normal bioprostheses function 1 year later. MAIVF-P coronary compression is rare. In this case, three-dimensional echocardiography facilitated the diagnosis of an asymptomatic but life-threatening LM trunk compression, which was confirmed with angiography. Fig 1.

No abstract

OBJECTIVE(S): This study was designed to evaluate prevalence and determinants of reduced functional capacity, in patients who underwent restrictive mitral valve annuloplasty (RMA) for severe ischemic mitral regurgitation (IMR). METHODS: Between January 2008 and December 2015, 90 patients with severe ischemic mitral regurgitation underwent coronary artery bypass grafting and restrictive mitral valve annuloplasty. After a mean period of 3.5 +/- 2.4years, cardiopulmonary exercise testing (CPET) was performed to assess peak oxygen consumption (VO2 max). RESULTS: At five years, survival was 68.8+/-5.3%. The mean VO2 max was 17.4+/-4 ml/kg/min (76.3+/-2% of the age predicted) but varied widely (32% to 121% of predicted) and was markedly reduced (<80% of predicted) in 37 patients (63%). Linear regression identifiedkidney function (Creatinine clearance, p < 0.01), preoperative functional capacity (NYHA > 4, p = 0.01), triple vessel disease (p = 0.03), BMI (p < 0.01), preoperative left ventricular end-diastolic volume (p = 0.04) and left ventricular systolic diameter (p = 0.04) as independent determinants of reduced VO2 max. No patients needed a mitral valve reoperation, freedom from more than moderate mitral regurgitation was 83.5+/-6.7 % at 5 years. CONCLUSIONS: Even with a relative low rate of IMR recurrence, functional capacity quantitatively assessed by CPET is markedly reduced in nearly two out of three patients after restrictive mitral valve annuloplasty. Reduced peak VO2 is independently determined by patient comorbidity, extensive coronary disease, left ventricle dimensions and preoperative functional status, but not by recurrence of IMR.