Frequency of screening and SBT Technique Trial-North American Weaning Collaboration (FAST-NAWC): an update to the protocol and statistical analysis plan.

BACKGROUND: This update summarizes key changes made to the protocol for the Frequency of Screening and Spontaneous Breathing Trial (SBT) Technique Trial-North American Weaning Collaborative (FAST-NAWC) trial since the publication of the original protocol. This multicenter, factorial design randomized controlled trial with concealed allocation, will compare the effect of both screening frequency (once vs. at least twice daily) to identify candidates to undergo a SBT and SBT technique [pressure support + positive end-expiratory pressure vs. T-piece] on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American intensive care units. METHODS/DESIGN: Protocols for the pilot, factorial design trial and the full trial were previously published in J Clin Trials ( https://doi.org/10.4172/2167-0870.1000284 ) and Trials (https://doi: 10.1186/s13063-019-3641-8). As planned, participants enrolled in the FAST pilot trial will be included in the report of the full FAST-NAWC trial. In response to the onset of the coronavirus disease of 2019 (COVID-19) pandemic when approximately two thirds of enrollment was complete, we revised the protocol and consent form to include critically ill invasively ventilated patients with COVID-19. We also refined the statistical analysis plan (SAP) to reflect inclusion and reporting of participants with and without COVID-19. This update summarizes the changes made and their rationale and provides a refined SAP for the FAST-NAWC trial. These changes have been finalized before completion of trial follow-up and the commencement of data analysis. TRIAL REGISTRATION: Clinical Trials.gov NCT02399267.

Effect of preoperative renin-angiotensin system blockade on vasoplegia after cardiac surgery: A systematic review with meta-analysis.

BACKGROUND: Vasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system (RAS) blockers [angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARB)] is still debated. AIM: To update and summarize data on the effect of preoperative use of RAS blockers on incident vasoplegia. METHODS: All published studies from MEDLINE, EMBASE, and Web of Science providing relevant data through January 13, 2021 were identified. A random-effects meta-analysis method was used to pool estimates, and post-cardiac surgery shock was differentiated from vasoplegia. RESULTS: Ten studies reporting on a pooled population of 15672 patients (none looking at ARBs exclusively) were included in the meta-analysis. All were case-control studies. Use of ACEIs was associated with an increased risk of vasoplegia [pooled adjusted odds ratio (Aor) of 2.06, 95%CI: 1.45-2.93] and increased inotropic/vasopressor support requirement (pooled aOR 1.19, 95%CI: 1.10-1.29). Post-cardiac surgery shock was increased in the presence of left ventricular dysfunction (pooled aOR 2.32, 95%CI: 1.60-3.36; I 2 49%) but not increased by the use of beta blockers (pooled aOR 0.78, 95%CI: 0.36-1.69; I 2 77%). Two randomized control trials (RCTs), not eligible for the meta-analysis, did not show an association between continuation of RAS blockers and vasoplegia. CONCLUSION: Preoperative continuation of ACEIs is associated with an increased need for inotropic support postoperatively and with an increased risk of vasoplegia in observational studies but not in RCTs. The absence of a consensus definition of vasoplegia should lead to the use of perioperative cardiovascular monitoring when designing RCTs to better understand this discrepancy.

Addition of high-intensity interval training to a moderate intensity continuous training cardiovascular rehabilitation program after ischemic cerebrovascular disease: A randomized controlled trial.

Introduction: Moderate intensity continuous training (MICT) is usually recommended for stroke or transient ischemic attack (TIA) patients. High intensity interval training (HIIT) has emerged as a potentially effective method for increasing cardiorespiratory fitness (CRF) among clinical populations. Its effectiveness remains to be demonstrated after stroke. A combined program of HIIT and MICT was designed to create a realistic exercise program implemented for a clinical setting to help patients become more active. Purpose: This study aimed to compare the effects of a 6-month exercise program with either MICT only or a combination of HIIT and MICT and a control group in terms of CRF, cardiovascular risk factors, functionality, cognitive function (Montreal Cognitive Assessment) and depression markers (Hospital Anxiety and Depression Scale). Methods: This randomized controlled trial started with 52 participants (33 men and 19 women, mean age: 69.2 ± 10.7) divided into three groups: HIIT + MICT combined, MICT, and control. Both exercise groups consisted of 4 weekly sessions including supervised and at-home exercise. Outcomes were assessed at T0 (baseline measure), T6 (end of exercise protocols), and T12 (follow-up), 40 participants having completed the 12-month follow-up. Results: At T6, both HIIT+MICT and MICT programs provided a similar increase of CRF (3 ml·min-1·kg-1) from baseline (p < 0.01), while the control group showed a global slight decrease. Despite some decrease of CRF at T12 compared to T6, improvement persisted 6 months post-intervention (HIIT + MICT: p < 0.01 and MICT: p < 0.05). The control group decreased compared with baseline (p < 0.05). The two exercise programs induced a comparable increase in self-reported physical activity and a decrease in anxiety and depression markers. Participants in HIIT + MICT and MICT programs declared a good degree of acceptability assessed by the Acceptability and Preferences Questionnaire. Conclusion: A 6-month HIIT + MICT combined program and a standard MICT program induced similar improvements in CRF, self-reported physical activity and anxiety and depression markers among patients with prior ischemic stroke or TIA compared with a control group. These effects appear to persist over time. Addition of HIIT was safe and considered acceptable by participants. Our results do not support any superiority of the combination HIIT + MICT nor disadvantage vs. MICT in this population.

Biventricular thrombosis and survival after two different mechanical supports before heart transplantation.

Patient survival from biventricular thrombosis is possible using mechanical support followed by cardiac transplantation.

Does the full-time presence of an intensivist lead to better outcomes in the cardiac surgical intensive care unit?

OBJECTIVE: The study objective was to compare clinical outcomes in a dedicated adult cardiac surgery intensive care unit before and after the implementation of 24-hour intensivist coverage. METHODS: Between 2008 and 2016, 16,454 consecutive adult patients were admitted to the cardiac surgery intensive care unit after cardiac surgery. During this period, postoperative patients in the cardiac surgery intensive care unit were managed by intensivists during the day (group A); in July 2010, the nighttime coverage was transferred from the hands of residents and fellows to intensivists (group B). Postoperative outcomes before and after this change using 1-to-1 propensity score matching were examined. Patients were stratified a priori into low- and high-risk (<5% and ≥5% predicted mortality) based on the European System for Cardiac Operative Risk Evaluation II. RESULTS: Matched patients in group A had significantly higher cardiac surgery intensive care unit (2.1% vs 1.4%, P = .01) and in-hospital (2.7% vs 1.8%, P = .008) mortality. This higher mortality was only observed among high-risk group A patients who had significantly higher rates of cardiac surgery intensive care unit mortality (6.8% vs 4.1%, P = .01) and in-hospital mortality (8.5% vs 5.3%, P = .01) compared with the high-risk group B. The median duration of mechanical ventilation (5.8 vs 4.3 hours, P < .0001) and the risk of prolonged ventilation greater than 48 hours (5.3% vs 4%, P = .008) were significantly higher among group A patients; this higher rate of respiratory adverse events was observed in all strata of preoperative risk. CONCLUSIONS: In this large cohort of patients admitted to a dedicated adult cardiac surgery intensive care unit, 24-hour intensivist coverage was associated with reduced mortality among patients with an expected operative mortality 5% or greater. These data suggest that preoperative risk stratification and adaptive cardiac surgery intensive care unit physician staffing may result in improved clinical outcomes and optimized hospital resource use.

Late Infection of an Atrial Septal Defect Closure Device: A Possible Complication.

Atrial septal defect is a common congenital heart defect. In the late 1990s, percutaneous closure became available and eventually the treatment of choice. The procedure is considered safe because of its low incidence of complications. Infection rate is extremely low and occurs typically early after device implantation. Herein we present a case of late and dramatic infection of an Amplatzer Septal Occluder (St Jude Medical). This case illustrates that infection remains possible a long time after atrial septal defect occlusion despite theoretical device endothelialization.

Transcatheter reduction of paravalvular leaks: a systematic review and meta-analysis.

BACKGROUND: Significant paravalvular leak (PVL) after surgical valve replacement can result in intractable congestive heart failure and hemolytic anemia. Because repeat surgery is performed in only few patients, transcatheter reduction of PVL is emerging as an alternative option, but its safety and efficacy remain uncertain. In this study we sought to assess whether a successful transcatheter PVL reduction is associated with an improvement in clinical outcomes. METHODS: We identified 12 clinical studies that compared successful and failed transcatheter PVL reductions in a total of 362 patients. A Bayesian hierarchical meta-analysis was performed using cardiac mortality as a primary end point. The combined occurrence of improvement in New York Heart Association functional class or hemolytic anemia and the need for repeat surgery, were used as secondary end points. RESULTS: A successful transcatheter PVL reduction was associated with a lower cardiac mortality rate (odds ratio [OR], 0.08; 95% credible interval [CrI], 0.01-0.90) and with a superior improvement in functional class or hemolytic anemia, compared with a failed intervention (OR, 9.95; 95% CrI, 2.10-66.73). Fewer repeat surgeries were also observed after successful procedures (OR, 0.08; 95% CrI, 0.01-0.40). CONCLUSIONS: A successful transcatheter PVL reduction is associated with reduced all-cause mortality and improved functional class in patients deemed unsuitable for surgical correction.

Role of echocardiography in acute myocardial infarction.

Echocardiography is a valuable tool in diagnosing acute coronary syndrome in patients presenting with chest pain in the emergency department. After acute myocardial infarction (MI), echocardiography provides substantial information regarding risk stratification, hemodynamic assessment, detection of mechanical complications related to acute MI, and long-term prognosis. It also helps in guiding therapy in patients after MI. However, it provides limited value in less than 10% of patients because of poor image quality. Contrast agent can and should be used to improve the accuracy of echocardiographic assessment.

Beneficial effects of long-term use of the antioxidant probucol in heart failure in the rat.

BACKGROUND: Congestive heart failure (CHF) is a disease that is characterized by progressive left ventricular (LV) dysfunction and dilatation. Oxidative stress is thought to contribute to the progression of CHF, and antioxidants have been shown to have beneficial effects when started early after myocardial infarction (MI). In this study, we tested whether the powerful antioxidant probucol would attenuate progression of CHF once it was established after MI in the rat. METHODS AND RESULTS: Ligation of a coronary artery was used to create an MI in rats (n=266). Survivors were then randomized 20 days after MI to either probucol 61 mg. kg(-1). d(-1) or vehicle and followed up for a total of 100 days after MI. Studies of cardiac hemodynamics, LV remodeling, cardiac apoptosis and morphology, systemic neurohumoral activation, oxidative stress, and renal function were then evaluated. Probucol improved LV function (LV maximum rate of pressure rise from 3103 to 4250 mm Hg/s, P<0.05, and LV end-diastolic pressure decrease from 28 to 24 mm Hg, P<0.05), reduced pulmonary weights, prevented right ventricular systolic hypertension, and preserved renal function compared with vehicle. Probucol also prevented LV dilatation, prevented wall thinning (1.70 versus 1.42 mm, P<0.05), reduced cardiac fibrosis and cardiac apoptosis, attenuated increased myocardial cell cross-sectional area, and increased scar thickness. CONCLUSIONS: In chronic CHF, probucol exerts multiple beneficial morphological effects that result in better LV remodeling and function, reduced neurohumoral activation, and preserved renal function.

Improved post-myocardial infarction survival with probucol in rats: effects on left ventricular function, morphology, cardiac oxidative stress and cytokine expression.

OBJECTIVES: The goal of this study was to evaluate whether reducing the potentially deleterious effects of oxidative stress with the potent anti-oxidant probucol improves prognosis after myocardial infarction (MI) in rats. BACKGROUND: Oxidative stress has been documented in patients early and late after MI, particularly when it is associated with congestive heart failure. METHODS: Rats surviving acute MIs for 24 h (n = 247) were assigned to vehicle or probucol (61 mg/kg, daily) for four weeks, at which time cardiac hemodynamic, morphologic and molecular measurements were done. RESULTS: In rats with large MIs, probucol improved survival (87.9%) when compared with vehicle (50.6%) (p < 0.001). Probucol also partially preserved left ventricular (LV) systolic but not diastolic function. Probucol increased scar thickness and decreased cardiac fibrosis but did not modify LV hypertrophy or dilation. Finally, probucol decreased cardiac oxidative stress, as assessed by measuring cardiac malondialdehydes, and decreased the cardiac expression of the pro-inflammatory cytokines interleukin (IL)-1beta and IL-6 but did not modify fetal gene re-expression in rats with large MIs. CONCLUSIONS: This study indicates that the anti-oxidant probucol markedly improves post-MI survival in rats despite few demonstrable effects on cardiac remodeling or hemodynamics. Its beneficial effects may, however, be associated with reduced cardiac fibrosis, oxidative stress and expression of pro-inflammatory cytokines.

Long-term effects of carvedilol on left ventricular function, remodeling, and expression of cardiac cytokines after large myocardial infarction in the rat.

Carvedilol (20 mg/kg, bid) or vehicle was given to rats surviving a myocardial infarction (MI) 24 h (n = 409). In rats with large MI, carvedilol partially preserved left ventricular (LV) function and intrinsic myocardial contractility and reactivity to beta-adrenergic stimulation. Carvedilol led to scar thickening, increased LV hypertrophy, and decreased cardiac fibrosis but did not prevent LV dilatation. Carvedilol reduced cardiac expression of interleukin-1beta but did not prevent cardiac fetal gene re-expression or modify cardiac oxidative stress. Despite these beneficial effects, carvedilol decreased survival (38.8%, versus vehicle, 50.6%) due to excessive early mortality. Thus, post-MI carvedilol has many beneficial effects, however, in this study it increased post-MI mortality, perhaps due to excessive hypotension.