Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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Background-Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI).Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality. Methods and Results-We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (Ͼ3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDE periphery ). After a median follow-up of 2.

Background-Contrast-enhanced cardiac magnetic resonance imaging (CMR) can determine the extent of myocardial scar from infarction (MI). However, the prognostic significance of unrecognized myocardial scar by CMR in patients without a history of MI is unknown. Methods and Results-One hundred ninety-five patients without a known prior MI underwent CMR for assessment of left ventricular (LV) function and late gadolinium enhancement (LGE). We assessed the prognostic value of LGE and other CMR variables beyond the strongest clinical predictors and built the best overall models for major adverse cardiac events (MACE) and cardiac mortality.

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BackgroundPatients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular events. The aim of the study was to assess whether global longitudinal strain (GLS) provides prognostic value in these patients.MethodsA total of 247 T2DM patients without history of cardiovascular complications and participated in the CDATS study were prospectively enrolled. Left ventricular (LV) systolic function was assessed by LV ejection fraction and speckle tracking derived LV systolic GLS. Diastolic function was assessed by E/E′ ratio defined as the passive trans-mitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus. Cardiovascular event included acute coronary syndrome, cerebrovascular stroke, hospitalization for heart failure and cardiovascular death.ResultsA total of 18 cardiovascular events occurred during a median follow-up duration of 33 months. Both E/E′ ratio [hazard ratio (HR) 1.15, P < 0.01] and GLS (HR 1.39, P < 0.01) were independently associated with cardiovascular events. Importantly, GLS provided incremental prognostic information in addition to clinical data, HbA1c and E/E′ ratio (Chi square 77.46, P = 0.04). Receiver-operator characteristic curve analysis demonstrated that E/E′ ratio [area under curve (AUC) 0.66, P = 0.03] and GLS (AUC 0.72, P < 0.01) were strong predictors of cardiovascular events. Kaplan–Meier analysis showed that patients with E/E′ > 13.6 or GLS > −17.9 % were associated with cardiovascular events. The presence of either a high E/E′ ratio or an impaired GLS provides an excellent negative predictive value of cardiovascular events in these patients.ConclusionsIn T2DM patients with no history of cardiovascular disease, impaired GLS was associated with cardiovascular events and provided incremental prognostic value.