Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov , NCT04327388 ; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 1...

In order to obtain accurate diagnosis, treatment and prognostication in many cardiac conditions, there is a need for assessment of left ventricular (LV) filling pressure. While systole depends on ejection function of LV, diastole and its disturbances influence filling function and pressures. The commonest condition that represents the latter is heart failure with preserved ejection fraction in which LV ejection is maintained, but diastole is disturbed and hence filling pressures are raised. Significant diastolic dysfunction results in raised LV end-diastolic pressure, mean left atrial (LA) pressure and pulmonary capillary wedge pressure, all referred to as LV filling pressures. Left and right heart catheterization has traditionally been used as the gold standard investigation for assessing these pressures. More recently, Doppler echocardiography has taken over such application because of its noninvasive nature and for being patient friendly. A number of indices are used to achieve accurate assessment of filling pressures including: LV pulsed-wave filling velocities (E/A ratio, E wave deceleration time), pulmonary venous flow (S wave and D wave), tissue Doppler imaging (E' wave and E/E' ratio) and LA volume index. LA longitudinal strain derived from speckle tracking echocardiography (STE) is also sensitive in estimating intracavitary pressures. It is angle-independent, thus overcomes Doppler limitations and provides highly reproducible measures of LA deformation. This review examines the application of various Doppler echocardiographic techniques in assessing LV filling pressures, in particular the emerging role of STE in assessing LA pressures in various conditions, e.g., HF, arterial hypertension and atrial fibrillation.

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ObjectivePulmonary congestion is the main cause of hospital admission in patients with heart failure (HF). Lung ultrasound (LUS) is a useful tool to identify subclinical pulmonary congestion. We evaluated the usefulness of LUS in addition to physical examination (PE) in the management of outpatients with HF.MethodsIn this randomised multicentre unblinded study, patients with chronic HF and optimised medical therapy were randomised in two groups: ‘PE+LUS’ group undergoing PE and LUS and ‘PE only’ group. Diuretic therapy was modified according to LUS findings and PE, respectively. The primary endpoint was the reduction in hospitalisation rate for acute decompensated heart failure (ADHF) at 90-day follow-up. Secondary endpoints were reduction in NT-proBNP, quality-of-life test (QLT) and cardiac mortality at 90-day follow-up.ResultsA total of 244 patients with chronic HF and optimised medical therapy were enrolled and randomised in ‘PE+LUS’ group undergoing PE and LUS, and in ‘PE only’ group. Thirty-seven primary outcome events occurred. The hospitalisation for ADHF at 90 day was significantly reduced in ‘PE+LUS’ group (9.4% vs 21.4% in ‘PE only’ group; relative risk=0.44; 95% CI 0.23 to 0.84; p=0.01), with a reduction of risk for hospitalisation for ADHF by 56% (p=0.01) and a number needed to treat of 8.4 patients (95% CI 4.8 to 34.3). At day 90, NT-proBNP and QLT score were significantly reduced in ‘PE+LUS’ group, whereas in ‘PE only’ group both were increased. There were no differences in mortality between the two groups.ConclusionsLUS-guided management reduces hospitalisation for ADHF at mid-term follow-up in outpatients with chronic HF.