Association Between Preexisting Heart Failure With Reduced Ejection Fraction and Fluid Administration Among Patients With Sepsis

IMPORTANCE: Intravenous fluid administration is recommended to improve outcomes for patients with septic shock. However, there are few data on fluid administration for patients with preexisting heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To evaluate the association between preexisting HFrEF, guideline-recommended intravenous fluid resuscitation, and mortality among patients with community-acquired sepsis and septic shock. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted of adult patients hospitalized in an integrated health care system from January 1, 2013, to December 31, 2015, with community-acquired sepsis and preexisting assessment of cardiac function. Follow-up occurred through July 1, 2016. Data analyses were performed from November 1, 2020, to August 8, 2022. EXPOSURES: Preexisting heart failure with reduced ejection fraction (≤40%) measured by transthoracic echocardiogram within 1 year prior to hospitalization for sepsis. MAIN OUTCOMES AND MEASURES: Multivariable models were adjusted for patient factors and sepsis severity and clustered at the hospital level to generate adjusted odds ratios (aORs) and 95% CIs. The primary outcome was the administration of 30 mL/kg of intravenous fluid within 6 hours of sepsis onset. Secondary outcomes included in-hospital mortality, intensive care unit admission, rate of invasive mechanical ventilation, and administration of vasoactive medications. RESULTS: Of 5278 patients with sepsis (2673 men [51%]; median age, 70 years [IQR, 60-81 years]; 4349 White patients [82%]; median Sequential Organ Failure Assessment score, 4 [IQR, 3-5]), 884 (17%) had preexisting HFrEF, and 2291 (43%) met criteria for septic shock. Patients with septic shock and HFrEF were less likely to receive guideline-recommended intravenous fluid than those with septic shock without HFrEF (96 of 380 [25%] vs 699 of 1911 [37%]; P \u3c .001), but in-hospital mortality was similar (47 of 380 [12%] vs 244 of 1911 [13%]; P = .83). In multivariable models, HFrEF was associated with a decreased risk-adjusted odds of receiving 30 mL/kg of intravenous fluid within the first 6 hours of sepsis onset (aOR, 0.63; 95% CI, 0.47-0.85; P = .002). The risk-adjusted mortality was not significantly different among patients with HFrEF (aOR, 0.92; 95% CI, 0.69-1.24; P = .59) compared with those without, and there was no interaction with intravenous fluid volume (aOR, 1.00; 95% CI, 0.98-1.03; P = .72). CONCLUSIONS AND RELEVANCE: The results of this cohort study of patients with community-acquired septic shock suggest that preexisting HFrEF was common and was associated with reduced odds of receiving guideline-recommended intravenous fluids

Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors

Background: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. Methods: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. Results: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk−1, p = .024, 382.2 MET-min∙wk−1, p = .010, and 264.1 MET-min∙wk−1, p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, −1.6 kg, p = .040, and −.6 kg/m2, p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p= .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p=.007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, −.38 mmol∙L−1, p=.001; and −.3 mmol∙L−1, p=.023, respectively). Conclusions: We found that home-based PA resulted in significant albeit small to moderate improvements in selfreported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care

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