Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Associated factors and clinical outcomes in mechanical circulatory support use in patients undergoing high risk on-pump cardiac surgery: Insights from the LEVO-CTS trial.

BACKGROUND: We describe variables and outcomes associated with peri-operative mechanical circulatory support (MCS) utilization among patients enrolled in the Levosimendan in patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial. METHODS: In the LEVO-CTS trial, MCS utilization (defined as intra-aortic balloon pump, extracorporeal membrane oxygenation, or surgical ventricular assist device) within 5 days of surgery was examined. The association between MCS use and outcomes including 90-day mortality, 30-day renal-replacement therapy, and hospital and critical stay length of stay were determined. RESULTS: Among the 849 patients from 70 centers randomized to levosimendan or placebo, 85 (10.0%) patients were treated with MCS (71 intra-aortic balloon pump, 7 extracorporeal membrane oxygenation, 7 ventricular assist device); with 89.4% started on post-operative day 0. Inter-institutional use ranged from 0% to 100%. Variables independently associated with MCS utilization included combined coronary artery bypass grafting and valve surgery (adjusted odds ratio [OR] 2.73, 95% confidence interval [CI] 1.70-4.37, P < .001), history of lung disease (OR 1.70, 95% CI 1.06-2.70, P = .029), and history of heart failure (OR 2.44, 95% CI 1.10-5.45, P = .027). Adjusted 90-day mortality (22.4% vs 4.1%, hazard ratio 6.11, 95% CI 3.95-9.44, P < .001) was higher, and median critical care length of stay (8.0 vs 4.0 days, P < .001) was longer in patients managed with MCS. CONCLUSIONS: In a randomized controlled trial of high-risk cardiac surgical patients in North America, we observed patient, and surgical variables associated with MCS utilization. MCS use was associated with a higher risk of post-operative mortality.

Use of antithrombotic therapy for secondary prevention in patients with stable atherosclerotic cardiovascular disease: Insights from the COordinated National Network to Engage Cardiologists in the antithrombotic Treatment of patients with CardioVascular Disease (CONNECT-CVD) study.

BACKGROUND: Although acetylsalicylic acid is the most commonly used antithrombotic agent for the secondary prevention of cardiovascular events, residual atherothrombotic risk has prompted a guideline recommendation for the addition of dual antiplatelet therapy (DAPT) or dual pathway inhibition (DPI) in high vascular risk patients. Accordingly, the CONNECT CVD quality enhancement initiative provides a contemporary "snapshot" of the clinical features and antithrombotic management of atherosclerotic cardiovascular disease (ASCVD) patients in Canada. METHODS: Canadian cardiologists (49 cardiologists from six provinces) undertook a retrospective chart audit of 10 ASCVD patients in their outpatient practice who met the Cardiovascular Outcomes for People Using Anticoagulation Strategy-like criteria from May 2018 to April 2019. RESULTS: Of the 492 (two cardiologists provided 11 patients) enroled, average age was 70 years, 25% were female, 39% had diabetes and 20% had atrial fibrillation. Prior revascularisation was common (percutaneous coronary artery intervention 61%, coronary artery bypass graft 39%), with 31% having multivessel disease. A total of 47% of patients had a Reduction of Atherothrombosis for Continued Health bleeding score of ≥11 (~2.8% risk of serious bleeding at 2 years). Single antiplatelet therapy (SAPT) alone was most commonly used (62%), while 22% were on DAPT alone. In total, 22% were on oral anticoagulation (OAC), with 16% being on non-vitamin K oral anticoagulant alone, 5% on DPI and 1% received triple therapy. CONCLUSIONS: In contemporary Canadian clinical practice of stable ASCVD patients, a large number of patients receive antithrombotic therapy other than SAPT. Further efforts are required to guide the appropriate selection of patients in whom more potent antithrombotic therapies may safely reduce residual risk.

Adalimumab for orbital myositis in a patient with Crohn's disease who discontinued infliximab: a case report and review of the literature.

BACKGROUND: Orbital myositis is a rare extra-intestinal manifestation of inflammatory bowel disease. Seventeen cases of Crohn's disease associated orbital myositis and 3 cases of ulcerative colitis associated orbital myositis have been reported in the published literature since 1970. We report the use of adalimumab (Abbott, Canada, Inc.) for orbital myositis in a patient with Crohn's disease who discontinued infliximab (Janssen, Canada, Inc.) and review of the published literature. CASE PRESENTATION: A 35 year-old male with a 7-year history of Crohn's disease was treated with an ileocolonic resection and re-anastomosis followed by infliximab which maintained full endoscopic and clinical remission for four years. After stopping the infliximab for infusion-related reactions he presented with 3-day history of severe right eye pain, pain with ocular movement, proptosis, and conjunctival injection. He had no intestinal symptoms and endoscopic assessment revealed no active luminal disease. CT of the orbit revealed an enlarged right medial rectus muscle with tendonous involvement and a diagnosis of orbital myositis was made. Treatment with 80 mg per day prednisone with tapering dose and adalimumab, induction and maintenance, resulted in rapid resolution of the orbital myositis and ocular symptoms with no recurrences on follow-up at 10 months. CONCLUSIONS: The current case demonstrates a rare extraintestinal manifestation of Crohn's disease, orbital myositis, and its temporal relationship to the discontinuance of infliximab therapy and its successful treatment, without recurrence with tapering prednisone and adalimumab.

Adenosine-mediated inhibition of 5'-AMP-activated protein kinase and p38 mitogen-activated protein kinase during reperfusion enhances recovery of left ventricular mechanical function.

Attenuation of excessive rates of myocardial glycolysis limits proton production and Ca(2+) overload during reperfusion and improves recovery of post-ischemic left ventricular (LV) function. In order to elucidate mechanisms underlying glycolytic inhibition by adenosine (ADO), this study tested the hypothesis that the beneficial effects of ADO are due to Ser/Thr protein phosphatase (PP)-mediated inhibition of 5'-AMP-activated protein kinase (AMPK) and phosphofructokinase-2 (PFK-2). In isolated perfused working rat hearts subjected to global ischemia (GI) and reperfusion, ADO (500µmol/l), added 5min prior to the onset of GI and present throughout reperfusion, inhibits glycolysis and proton production during reperfusion and improves post-ischemic LV work. These metabolic effects of ADO are also evident during aerobic perfusion. Assays of glycolytic intermediates show that ADO-induced glycolytic inhibition occurs at the step catalyzed by PFK-1, an effect mediated by reduced activation of PFK-2 by AMPK. The PP1 and PP2A inhibitors, cantharidin (5µmol/l) or okadaic acid (0.1µmol/l), added 10min prior to ADO prevent ADO-induced inhibition of glycolysis and AMPK, as well as ADO-induced cardioprotection. ADO also inhibits p38 MAPK phosphorylation during reperfusion in a cantharidin-sensitive manner, and pharmacological inhibition of p38 MAPK (by SB202190, 10µmol/l) during reperfusion also reduces glycolysis and is cardioprotective. These results indicate that attenuation of glycolysis during reperfusion and cardioprotection can be achieved by inhibition of the stress kinases, AMPK and p38 MAPK.

Cardiorenal Interactions: A Review.

A complex interaction occurs between cardiac and renal function. They are intricately tied together, and a range of disorders in both the heart and kidneys can alter the function of the other. The pathophysiology is complex, and these conditions are termed cardiorenal syndromes. They can be acute and/or chronic in nature, they result in and from hemodynamic consequences, systemic congestion, and metabolic abnormalities, and they lead to dysfunction of both the heart and kidneys. The aim of this article is to provide a review for cardiologists and intensivists who are treating patients for whom cardiac and renal interactions may complicate their picture. We review acute kidney injuries, management of the complications of renal dysfunction, renal replacement therapy, and cardiorenal syndromes.

Il existe une interaction complexe entre la fonction cardiaque et la fonction rénale. Elles sont étroitement liées, et un éventail de troubles cardiaques et rénaux peuvent altérer la fonction de l'autre. Ces maladies dont la physiopathologie est complexe sont appelées syndromes cardiorénaux. Elles peuvent être aiguës et/ou chroniques de nature, elles entraînent des conséquences hémodynamiques, une congestion systémique et des anomalies métaboliques, ou résultent de celles-ci, et elles mènent à la dysfonction du cœur ou des reins. L'objectif du présent article est d'offrir une revue aux cardiologues et aux intensivistes qui traitent des patients dont les interactions cardiaques et rénales peuvent compliquer leur tableau. Nous passons en revue les atteintes rénales aiguës, la prise en charge des complications de la dysfonction rénale, le traitement de substitution rénale et les syndromes cardiorénaux.

Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades.

Importance: Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied. Objective: To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time. Data Source: Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology. Study Selection: All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included. Data Extraction and Synthesis: Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine. Main Outcomes and Measures: The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis. Results: Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point. Conclusions and Relevance: The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.

Prospective validation and refinement of the APPROACH cardiovascular surgical intensive care unit readmission score.

PURPOSE: The APPROACH cardiovascular surgical intensive care unit (CVICU) readmission score has excellent discrimination and calibration for CVICU readmission after discharge to a surgical ward; however, it has not been prospectively validated. MATERIAL AND METHODS: In a prospective consecutive cohort of 805 patients ≥18 years admitted to the CVICU after coronary artery bypass and/or valvular surgery, the APPROACH CVICU readmission score was calculated at the time of discharge to a surgical ward. The study compared observed versus predicted CVICU readmission and the model discrimination was evaluated using AUC c-index. The incremental prognostic utility of 6 pre-specified prospectively collected respiratory (re-intubation, tracheostomy, oxygen at discharge) and hemodynamic variables (heart rate, systolic blood pressure, inotropes at discharge) were tested using net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 37 (4.6%) patients were readmitted to the CVICU. The median CVICU length of stay (9.0 vs 2.0 days, p < .001) and all-cause in-hospital mortality (8.1% vs 0.4%, p < .001) was higher among readmitted patients. The model had good discrimination (c-index = 0.748). Systolic blood pressure at discharge yielded the largest improvement in model discrimination (c-index = 0.782; Hosmer-Lemshow p = .749). CONCLUSIONS: In a prospective validation cohort, the APPROACH CVICU readmission risk score had good discrimination and could be operationalized in future research and clinical practice.

Acute Coronary Syndromes and Heart Failure Critical Care Units Utilization and Outcomes in Teaching and Community Hospitals: A National Population-Based Analysis.

Acute coronary syndromes (ACS) and heart failure (HF) are the leading diagnoses in patients admitted to critical care units (CCUs). Little is known about the differences between CCU resource use and outcomes across hospital types. The Canadian Institute for Health Information was used to identify patients hospitalized with primary diagnoses of ACS or HF. CCUs were categorized as teaching, large community, medium community, and small community hospitals. Outcomes included CCU rates of admission, use of critical care therapy/procedures, and in-hospital mortality. Among 204,900 patients hospitalized with ACS or HF, 73,338 (35.8%, hospital range 0% to 81.4%) were admitted to CCUs, and it varied across hospital types: 41.0% in teaching, 30.0% in large, 45.4% in medium, and 30.9% in small community hospitals (P < 0.001). The percentage of patients admitted to CCUs who received critical care therapies in teaching, large, medium, and small hospitals were as follows: 73.6%, 50.9%, 24.6%, and 8.8% (P < 0.0001). Compared with the in-hospital mortality rate for patients admitted to CCUs in teaching hospitals (8.2%), outcomes were worse for CCU patients in large (11.0%, adjusted odds ratio [aOR] 1.50; 95% CI, 1.19-1.90), medium (10.5%, aOR 1.56; 95% CI, 1.27-1.92), and small community hospitals (9.2%, aOR 1.59; 95% CI, 1.20-2.10). Patients admitted with ACS or HF to teaching hospital CCUs had a higher observed use of critical care therapies and lower mortality compared with community hospitals. These differences highlight the need to examine differences in CCU admission thresholds, resource utilization, and outcomes across hospitals types.

Noninvasive Fecal Immunochemical Testing and Fecal Calprotectin Predict Mucosal Healing in Inflammatory Bowel Disease: A Prospective Cohort Study.

BACKGROUND: The noninvasive biomarkers fecal immunochemical testing (FIT) and fecal calprotectin (FCP) are sensitive for prediction of mucosal inflammation in inflammatory bowel disease. However, neither test has yet been shown to independently and accurately predict mucosal healing (MH). We aimed to assess the specificity of noninvasive FIT and FCP for MH prediction. METHODS: In this prospective cohort study of adult inflammatory bowel disease outpatients presenting for colonoscopy, stool samples for FIT and FCP were collected 48 hours before endoscopy. Using MH defined by Simple Endoscopic Score for Crohn's disease (SES-CD = 0), Rutgeert's score (i0), and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS = 3), receiver operator characteristic curves were plotted, and sensitivity, specificity, positive and negative predictive values, and areas under the curve were calculated. Multivariate logistic regression analysis was used to develop a clinical model for noninvasively predicting MH. RESULTS: Eighty patients (40 Crohn's disease and 40 ulcerative colitis) were enrolled. The specificities of FIT <100 ng/mL and FCP <250 µg/g for MH were 0.57 (95% confidence interval, 0.38-0.74) and 0.77 (0.57-0.89), respectively. Positive predictive values for MH for FIT <100 ng/mL and FCP <250 µg/g were 0.78 (0.64-0.87) and 0.77 (0.58-0.90), respectively. In multivariate modeling, combining FIT, FCP, and clinical symptomatic remission improved specificity for MH to 0.90 (0.72-0.97) with positive predictive values of 0.84 (0.60-0.96). Areas under the curve for FIT was higher for patients with ulcerative colitis (0.88) than for patients with Crohn's disease (0.69, P = 0.05). CONCLUSIONS: FIT and FCP have similar performance characteristics for identifying MH. Combined, low FIT, low FCP, and clinical remission are specific for MH.

Northern Alberta remote teleglaucoma program: clinical outcomes and patient disposition.

OBJECTIVE: To review the diagnostic outcomes and clinical referral pathways of patients assessed and managed through a collaborative care patient-centred teleglaucoma program. STUDY DESIGN: Retrospective cohort study. METHODS: Eligible patients were those assessed by the referring optometrist or ophthalmologist to be open-angle glaucoma suspects or to have definite early open-angle glaucoma. A glaucoma specialist graded each case through virtual consultation. Clinical referral pathways were noted: in-person consultation with glaucoma specialist, repeat teleconsultation, collaborative glaucoma management with optometrist, or referral for nonglaucomatous ophthalmic pathology. RESULTS: A total of 247 patients were referred to the program from 2008 to 2012. Of all teleconsults, 31.1% were diagnosed with glaucoma, 42.1% were suspects, and 26.7% were unaffected. Of all patients, 27% were referred for in-person glaucoma evaluation; 69% of patients could be managed by their referring optometrist, with 48% of patients requiring repeat teleconsultation. Treatment was initiated before being seen for 87% of patients with definite glaucoma and 28% of glaucoma suspects. CONCLUSIONS: Of all patients seen through the remote teleglaucoma program, most did not require an in-person consultation with an ophthalmologist and could be managed through distance collaboration. For the approximately one third who were diagnosed with glaucoma based on virtual assessment, medication was started in the majority of cases and in-person consultation was arranged. Further studies to validate and consider cost-effectiveness of this system are under way.