Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effect of left and right lateral decubitus positions on mitral flow pattern by Doppler echocardiography in patients with systolic or diastolic dysfunction

Doppler echocardiographic asessment of the mitral valve provides a considerable amount of information regarding the diastolic filling characteristics of the left ventricle. Patients with congestive heart failure usually complain of increasing dyspnea in left lateral decubitis (LLD) position, compared with the right lateral decubitus (RLD) position which is called trepopnea. In this study, the effects of LLD and RLD positions on mitral flow velocities in patients with systolic or diastolic dysfunction were examined. Sixteen patients with systolic dysfunction (Group I), 16 patients with diastolic dysfunction (Group 2), and 16 normal subjects (control group) constituted the study group. Peak early diastolic (E) and atrial (A) flow velocities, EIA ratios, deceleration time (DT), flow duration (PD), the velocity time integral of mitral total flow during diastole (VTI), transmitral mean gradient during diastole (MGR) were calculated in each decubitis position. In group I; DT was shorter, VTI and FD were significantly lower and E/A ratio was significantly higher than normal control subjects in LLD position. In group I, RLD position resulted in an increase in DT (124.81 +/- 21.6, 155.6 +/- 23,p = 0.004), increase in VTI (0.13 +/- 0.03, 0.16 +/- 0.09, p = 0.02) and a decrease in E/A ratio (1.92 +/- 1, 1.62 +/- 0.88, p = 0.006) suggesting a decrease in left ventricular preload on changing position. On the other hand, no significant change on mitral flow pattern was detected after turning over the RLD position in patients with diastolic dysfunction. There was also no significant mitral flow change in the control group on RLD position. The results of this study suggest that the Doppler derived mitral flow pattern is significantly altered by a postural change from the LLD to RLD positions in patients with systolic dysfunction. This may help to explain the trepopnea in these patients

Etiology of portal venous thrombosis and budd-chiari syndrome in adults

WOS: 000356426904308

Use of intraventricular dispersion of the peak diastolic flow velocity as a marker of left ventricular diastolic dysfunction in patients with atrial fibrillation

The aim of this study was to evaluate the use of intraventricular dispersion of the peak diastolic Row velocity as a marker of left ventricular diastolic dysfunction in patients with atrial fibrillation. Regional diastolic Row velocity patterns at 1, 2, and 3 cm away from the mitral tip toward the apex were simultaneously recorded with the mitral flow velocity pattern by using pulsed Doppler echocardiography in 24 patients with atrial fibrillation before electrical or medical cardioversion. Echocardiographic examination was repeated after 10 to 30 days (ie, at the time of recovery of left atrial mechanical functions) after cardioversion of atrial fibrillation in all patients. Thirteen patients were found to have diastolic dysfunction; the remaining 11 patients with a normal E/A ratio constituted the control group. Afterward, the data recorded before the cardioversion were analyzed for each patient. in subjects with normal diastolic function, the peak diastolic flow velocity ((PDFV) at the mitral tips also was maintained at the positions 1 to 3 cm away from the tip In the left ventricular cavity (PDFV at the mitral tips: 0.84 m/s, PDFV at 3 cm: 0.85 m/s; P = .34). In contrast, the regional PDFV progressively decreased toward the apex- in patients with diastolic dysfunction (PDFV at the mitral tips: 0.82 m/s, PDFV at 3 cm: 0.63 m/s: p = .0004). Only 77% of the initial velocity was maintained at 3 cm away from the mitral tips in patients with diastolic dysfunction, whereas almost 100% of the: Initial velocity was preserved In patients with normal diastolic function (P < .001). These findings suggest that the assessment of the intraventricular decrease in mitral PDFV may be used as a reliable marker of diastolic dysfunction in patients with atrial fibrillation

Long-term (180-Day) outcomes in critically Ill patients with COVID-19 in the REMAP-CAP randomized clinical trial

Importance The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months