Efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19; a systematic review and meta-analysis of randomized clinical trials.

AIMS: Tocilizumab has emerged as an important therapy in treating patients with coronavirus disease (COVID-19). Our purpose was to evaluate the efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19. METHODS: We searched a variety of sources from 1 January 2020 to 5 May 2021. All randomized controlled trials that reported tocilizumab efficacy as a primary agent in COVID-19 patients were considered. RCTs had to include mortality events, incidence of mechanical ventilation and serious adverse events. Two reviewers were independently responsible for data extraction. Assessment of bias and certainty of evidence was carried out using the Cochrane Risk of Bias Tool and GRADE methodology. RR for mortality events was evaluated using a fixed-effects model. RESULTS: A total of 6837 patients were included from 10 RCTs, of which nine were peer-reviewed. Pooled risk ratio (RR) for all-cause mortality in patients with tocilizumab administration was RR = 0.88 (95% CI: 0.81-0.95, P = .0009). RR for incidence of mechanical ventilation at 28-30 days was 0.79 (95% CI: 0.71-0.88). Serious adverse events (SAE) with tocilizumab use were associated with lower RR (RR = 0.91, 95% CI: 0.76-1.09) but the certainty of evidence was downgraded to moderate due to serious risk of bias. CONCLUSION: In COVID-19 patients with moderate to critical COVID-19, use of tocilizumab reduces all-cause mortality and progression to mechanical ventilation. This efficacy was not associated with higher number of serious adverse events.

Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction.

BACKGROUND: The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF). METHODS: In 147 HF patients (mean age 61 ± 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m), and also in two groups according to EF (Group A: LVEF ≥ 45% and Group B: LVEF < 45%). RESULTS: In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (<300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF. CONCLUSION: In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.

Predictors of exercise capacity in patients with chronic heart failure.

BACKGROUND: Heart failure is a major and growing societal problem characterized by high mortality, frequent hospitalization, reduced quality of life and a complex therapeutic regimen. The six-minute walking test (6-MWT) may serve as a useful and reproducible test for assessing exercise capacity in heart failure patients and has been suggested as a simple, well-tolerated and inexpensive alternative to cardiopulmonary exercise testing (CPET). The CPET and 6-MWT are the most broadly used for assessing functional limitation in patients with heart failure. Echocardiography is well qualified to meet the growing need for noninvasive imaging in the expanding heart failure population. METHODS: This study included 132 consecutive patients (61 ± 10 years, 45% women) with stable heart failure. All patients underwent 6-MWT and Doppler echocardiographic examination on the same day. Clinical, biochemical and echocardiographic predictors were analyzed to assess predictors of exercise capacity. Patients were divided into two groups based on the 6-MWT distance. The first group comprised patients with limited exercise performance (≤ 300 m), and the second group, patients with good exercise performance (>300 m). RESULTS: In univariate analysis, patients' age [0.931 (0.895-0.968), P < 0.001], arterial hypertension [0.481 (0.239-0.967), P = 0.040], blood urea level [0.860 (0.759-0.975), P = 0.019], New York Heart Association (NYHA) class [0.441 (0.245-0.795), P = 0.006], early diastolic E wave [1.014 (1.000-1.029), P = 0.047], total isovolumic time (t-IVT) [0.868 (0.796-0.947), P = 0.001], Tei index [0.112 (0.028-0.450), P = 0.002], and E' of left-ventricular (LV) lateral wall [1.188 (1.099-1.400), P = 0.039] independently predicted poor 6-MWT performance (<300 m). In multivariate analysis, only patients' age [0.948 (0.902-0.996), P = 0.034], arterial hypertension [0.351 (0.133-0.922), P = 0.034], and t-IVT [0.828 (0.725-0.946), P = 0.005] independently predicted poor 6-MWT performance (<300 m). CONCLUSION: In chronic stable heart failure patients, in addition to age, systemic hypertension as well as LV asynchrony, as reflected by prolonged t-IVT, are independent predictors of poor exercise capacity.

MRSA endocarditis of bovine Contegra valved conduit: a case report.

BACKGROUND: Different techniques are used for the right ventricular outflow tract reconstruction, including homo- or porcine xenografts, which have several limitations. Contegra, a bovine jugular vein graft, is an interesting alternative to overcome these limitations. It consists of a bovine jugular vein with a naturally integrated valve in it. Isolated pulmonary valve endocarditis is extremely rare. CASE PRESENTATION: We report the case of a 20 years old male patient with acute endocarditis of bovine Contegra valved conduit, four years after right ventricular outflow tract reconstruction and atrial septal defect correction, associated with acute glomerulonephritis, renal failure and severe anemia, secondary to methicillin-resistant Staphylococcus aureus infection (MRSA). CONCLUSION: We present a complex patient with acute endocarditis of bovine Contegra valved conduit. We believe that the presentation of this case should encourage the researchers for the discussing of the implantation of this conduit and the prevention of endocarditis in these patients.