Background In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID‐19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low‐dose hydrocortisone on patient‐centred outcomes in adults with COVID‐19 and severe hypoxia. Methods In this multicentre, parallel‐group, placebo‐controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID‐19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/day) versus a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. Results The trial was terminated early when 30 out of 1,000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID‐19. At day 28, the median number of days alive without life support in the hydrocortisone versus placebo group were 7 versus 10 (adjusted mean difference: ‐1.1 days, 95% CI ‐9.5 to 7.3, p = 0.79); mortality was 6/16 versus 2/14; and the number of serious adverse reactions 1/16 versus 0/14. Conclusions In this trial of adults with COVID‐19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled.

Aims Left atrial (LA) fibrosis is a hallmark of atrial cardiomyopathy, and non-invasive surrogate measures of LA fibrosis are therefore needed. We investigated the association between four-dimensional (4D) echocardiographic LA measures and LA fibrosis. Methods and results A multimodality imaging substudy was performed in a randomized clinical trial (LOOP study), recruiting elderly participants with cardiovascular risk factors. LA late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging was used as a surrogate for LA fibrosis. 4D echocardiographic LA quantification was used to measure maximal and minimal LA volume (LAVmax and LAVmin, respectively), LA emptying fractions (LAEFtotal), and strain. Logistic regression was used to relate LA measures to high LA LGE (≥17 cm2). Of the 44 participants (mean age 76 years, 64% men, median LA LGE 13.1 cm2), 14 exhibited high LA LGE. These participants exhibited abnormalities in several LA functional measures but not LAVmax. In linear regressions, only increasing LAVmin, and decreasing LAEFtotal, and reservoir strain were associated with increasing LA LGE. Furthermore, increasing LAVmin was associated with a higher likelihood of high LA LGE [odds ratio (OR) = 1.19 (1.04–1.37)]. Decreasing LAEFtotal and reservoir strain were also associated with higher likelihood of LA LGE [OR = 1.18 (1.05–1.33)] and OR = 1.15 (1.02–1.30), per 1% decrease in LAEFtotal and reservoir strain, respectively]. These findings were consistent after multivariable adjustments. LAEFtotal provided the highest performance for detecting high LA LGE (area under the curve of 0.78). Conclusion LAVmin, LAEFtotal, and reservoir strain measured by 4D echocardiography are significantly associated with LA LGE. LAEFtotal provides the best performance for detecting high LA LGE.

Ventricular arrhythmia is one of the main causes of sudden cardiac death. Hence, identifying patients at risk of ventricular arrhythmias and sudden cardiac death is important but can be challenging. The indication for an implantable cardioverter defibrillator as a primary preventive strategy relies on the left ventricular ejection fraction as a measure of systolic function. However, ejection fraction is flawed by technical constraints and is an indirect measure of systolic function. There has, therefore, been an incentive to identify other markers to optimize the risk prediction of malignant arrhythmias to select proper candidates who could benefit from an implantable cardioverter defibrillator. Speckle-tracking echocardiography allows for a detailed assessment of cardiac mechanics, and strain imaging has repeatedly been shown to be a sensitive technique to identify systolic dysfunction unrecognized by ejection fraction. Several strain measures, including global longitudinal strain, regional strain, and mechanical dispersion, have consequently been proposed as potential markers of ventricular arrhythmias. In this review, we will provide an overview of the potential use of different strain measures in the context of ventricular arrhythmias.

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