Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health.

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.

The role of anticoagulation in preventing myocardial infarction and improving outcomes in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with cardiovascular (CV) complications including myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The infection is more severe in patients with pre-existing cardiovascular disease (CVD), where systemic inflammation due to cytokine storm, hypercoagulation, as well as high hematocrit and platelet (PLT) count may contribute to an increased CV risk. The authors hypothesize that anticoagulants and antiplatelets prevent miocardial infarction (MI) in patients with pre-existing CVD. METHODS: A cohort study enrolled patients with a confirmed diagnosis of COVID-19. Clinical and laboratory data, total and CV mortality, as well as MI incidence and treatment regimens were compared according to the time of hospitalization: 40-day period in April-May (Group 1) and in October-November (Group 2). RESULTS: A total of 195 patients were enrolled: 93 in Group 1, with 36.5%, and 102 in Group 2 with 38.2% pre-existing CVD. Group 1 was managed with infusion therapy; only 10.7% received anticoagulation. Group 2 received preventive anticoagulants, antiplatelets, and infusion therapy. In Group 1, seven cases of MI were recorded compared to only three in Group 2. No significant difference in overall mortality (4.3% vs 6.86%, p = 0.441) and MI incidence (7.5% vs 2.9%, p = 0.149) was found, but significant differences were seen in the incidence of severe and critically ill cases between the groups (69.9% and 7.5% vs 75.5% and 20.6%, p < 0.001). CONCLUSIONS: Poorer outcomes in the early COVID-19 wave were associated with inadequate anticoagulation due to lack of knowledge about the new virus. Despite significantly more severe cases, there was no significant difference in overall mortality and MI incidence in patients with anticoagulation.

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application.

While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow-fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore-size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected "free" MSCs, a model of systemic administration. Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with "free" MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Furthermore, application of this technology in two in vivo models did not require additional heparin in fully anticoagulated experimental animals to maintain target activated clotting time levels relative to heparin anticoagulated controls. Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time.

Thrombotic Complications of COVID-19 Infection: A Review.

The novel coronavirus (severe acute respiratory syndrome CoV-2 [SARS-CoV-2]), also known as COVID-19, is a single-stranded enveloped RNA virus that created a Public Health Emergency of International Concern in January 2020, with a global case burden of over 15 million in just 7 months. Infected patients develop a wide range of clinical manifestations-typically presenting with fever, cough, myalgia, and fatigue. Severely ill patients may fall victim to acute respiratory distress syndrome, acute heart injuries, neurological manifestations, or complications due to secondary infections. These critically ill patients are also found to have disrupted coagulation function, predisposing them to consumptive coagulopathies, and both venous and thromboembolic complications. Common laboratory findings include thrombocytopenia, elevated D-dimer, fibrin degradation products, and fibrinogen, all of which have been associated with greater disease severity. Many cases of pulmonary embolism have been noted, along with deep vein thrombosis, ischemic stroke, myocardial infarction, and systemic arterial embolism. The pathogenesis of coronavirus has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation. These patients are also faced with prolonged immobilization while staying in the hospital or intensive care unit. It is important to have a high degree of suspicion for thrombotic complications as patients may rapidly deteriorate in severe cases. Evidence suggests that prophylaxis with anticoagulation may lead to a lower risk of mortality, although it does not eliminate the possibility. The risks and benefits of anticoagulation treatment should be considered in each case. Patients should be regularly evaluated for bleeding risks and thrombotic complications.

Emerging mechanisms for the new coronavirus-related myocardial injury and ischemia: A review of the literature.

A history of cardiovascular comorbidity or experiencing acute cardiac injury during the coronavirus disease 2019 is accompanied by a poor prognosis. Also, it seems myocardial ischemia (or infarction) accounts for a major part of the cardiac involvement observed in this disease. Therefore, particular consideration is needed to protect the cardiovascular system during this pandemic. The gaps highlighted in this review are an issue to be explored through future research.

Is Increased Sleep Responsible for Reductions in Myocardial Infarction During the COVID-19 Pandemic?

The COVID-19 pandemic caused by the highly contagious SARS-CoV-2 virus has had devastating consequences across the globe. However, multiple clinics and hospitals have experienced a decrease in rates of acute myocardial infarction and corresponding cardiac catheterization lab activations, raising the question: Has the risk of myocardial infarction decreased during COVID? Sleep deprivation is known to be an independent risk factor for myocardial infarction, and sleep has been importantly impacted during the pandemic, possibly due to the changes in work-home life leading to a lack of structure. We conducted a social media-based survey to assess potential mechanisms underlying the observed improvement in risk of myocardial infarction. We used validated questionnaires to assess sleep patterns, tobacco consumption and other important health outcomes to test the hypothesis that increases in sleep duration may be occurring which have a beneficial impact on health. We found that the COVID-19 pandemic led to shifts in day/night rhythm, with subjects waking up 105 minutes later during the pandemic (p <0.0001). Subjects also reported going to sleep 41 minutes later during the pandemic (p <0.0001). These shifts led to longer duration of sleep during the COVID-19 pandemic. Before the pandemic, subjects reported sleeping 6.8 hours per night, which rose to 7.5 hours during the pandemic, a 44 minute or 11% increase (p <0.0001). We acknowledge the major negative health impact of the global pandemic but would advocate for using this crisis to improve the work and sleep habits of the general population, which may lead to overall health benefits for our society.