Ramping up Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from The Society of Thoracic Surgeons COVID-19 Task Force

The COVID-19 pandemic has had a profound global impact. Its rapid transmissibility has transformed healthcare delivery and forced countries to adopt strict measures to contain its spread. The vast majority of U.S. cardiac surgical programs have deferred all but truly emergent/urgent operative procedures in an effort to reduce the burden on the healthcare system and to mobilize resources to combat the pandemic surge. While the number of COVID-19 cases continues to increase worldwide, the incidence of new cases has begun to decline in many North American cities. This flattening of the curve has prompted interest in re-opening the economy, relaxing public health restrictions, and resuming non-urgent health care delivery

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Emerging group C and group G streptococcal endocarditis: A Canadian perspective

Objectives: The aim of this study was to determine the incidence of infective endocarditis (IE) in patients with bacteremia caused by group C and group G streptococci (GCGS) and to characterize the burden of disease, clinical characteristics, and outcomes through a case series of patients with GCGS IE. Methods: Individuals with blood cultures growing GCGS in Manitoba, Canada, between January 2012 and December 2015 were included. Clinical and echocardiographic parameters were collected retrospectively. IE was suspected or confirmed according to the modified Duke criteria. Results: Two hundred and nine bacteremic events occurred in 198 patients. Transthoracic echocardiography (TTE) was performed in 33%. Suspected or confirmed IE occurred in 6% of all patients and in 18% of those with TTE. Native valve infection was more common than prosthetic valve and device-related infections (75%, 17%, and 8%, respectively). Metastatic infection was observed in 64%, primarily to the lungs (57%), skin (43%), osteoarticular system (29%), and central nervous system (29%). Sepsis occurred in 58% and streptococcal toxic shock syndrome in 50% of those with IE, with overall mortality of 17%. Conclusions: IE from GCGS bacteremia is common and is frequently associated with severe disease, embolic events, and mortality. In the appropriate clinical context, GCGS bacteremic events should prompt investigation for IE. Keywords: Streptococcus dysgalactiae, Group C streptococci, Group G streptococci, Bacteremia, Infective endocarditi

Clonal Clusters and Virulence Factors of Group C and G Streptococcus Causing Severe Infections, Manitoba, Canada, 2012–2014

The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012–2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS

Decontamination of N95 masks for re-use employing 7 widely available sterilization methods.

The response to the COVID-19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted, with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability of 7 different decontamination methods: autoclave treatment, ethylene oxide gassing (ETO), low temperature hydrogen peroxide gas plasma (LT-HPGP) treatment, vaporous hydrogen peroxide (VHP) exposure, peracetic acid dry fogging (PAF), ultraviolet C irradiation (UVCI) and moist heat (MH) treatment to decontaminate a variety of different N95 masks following experimental contamination with SARS-CoV-2 or vesicular stomatitis virus as a surrogate. In addition, we sought to determine whether masks would tolerate repeated cycles of decontamination while maintaining structural and functional integrity. All methods except for UVCI were effective in total elimination of viable virus from treated masks. We found that all respirator masks tolerated at least one cycle of all treatment modalities without structural or functional deterioration as assessed by fit testing; filtration efficiency testing results were mostly similar except that a single cycle of LT-HPGP was associated with failures in 3 of 6 masks assessed. VHP, PAF, UVCI, and MH were associated with preserved mask integrity to a minimum of 10 cycles by both fit and filtration testing. A similar result was shown with ethylene oxide gassing to the maximum 3 cycles tested. Pleated, layered non-woven fabric N95 masks retained integrity in fit testing for at least 10 cycles of autoclaving but the molded N95 masks failed after 1 cycle; filtration testing however was intact to 5 cycles for all masks. The successful application of autoclaving for layered, pleated masks may be of particular use to institutions globally due to the virtually universal accessibility of autoclaves in health care settings. Given the ability to modify widely available heating cabinets on hospital wards in well-resourced settings, the application of moist heat may allow local processing of N95 masks

Adult Cardiac Surgery and the COVID-19 Pandemic: Aggressive Infection Mitigation Strategies Are Necessary in the Operating Room and Surgical Recovery

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Pre, intra, and post-operative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be utilized for ALL patients while local COVID-19 disease burden remains elevated

Surgical Triage and Timing for Patients with COVID: A Guidance Statement from the Society of Thoracic Surgeons

The coronavirus disease 2019 (COVID-19) pandemic continues to disrupt the provision of cardiac procedural services due to overwhelming interval surges in COVID-19 cases and the associated crisis of cardiac intervention deferment. Despite the availability of widespread testing, highly efficacious vaccines, and intensive public health efforts, the pandemic is entering its third year where new SARS-CoV-2 variants have increased the likelihood that patients scheduled for cardiac intervention will contract COVID-19 in the perioperative period. The Society of Thoracic Surgeons (STS) Workforce on Critical Care, the Workforce on Adult Cardiac and Vascular Surgery and the Canadian Society of Cardiac Surgeons have developed this document, endorsed by the STS and affirmed by the Society of Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology, to provide guidance for cardiac procedure deferment and intervention timing for preoperative patients diagnosed with COVID-19. This document is intended for the perioperative cardiac surgical team and outlines the present state of the pandemic, the impact of COVID-19 on intervention outcome, and offers a recommended algorithm for individualized cardiac procedure triage and timing