Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination’s prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory

Circadian Pattern of Acute Myocardial Infarction and Atrial Fibrillation in a Mediterranean Country: A study in Diabetic Patients

Background and objectives: The circadian pattern seems to play a crucial role in cardiovascular events and arrhythmias. Diabetes mellitus is a complex metabolic disorder associated with autonomic nervous system alterations and increased risk of microvascular and macrovascular disease. We sought to determine whether acute myocardial infarction (AMI) and atrial fibrillation (AF) follow a circadian pattern in diabetic patients in a Mediterranean country. Materials and Methods: This retrospective study included 178 diabetic patients (mean age: 67.7) with AMI or AF who were admitted to the coronary care unit. The circadian pattern of AMI and AF was identified in the 24-h period (divided in 3-h and 1-h intervals). Patients were also divided in 3 groups according to age; 40–65 years, 66–79 years and patients older than 80 years. A chi-square goodness-of-fit test was used for the statistical analysis. Results: AMI seems to occur more often in the midnight hours (21:00–23:59) (p < 0.001). Regarding age distribution, patients between 40 and 65 years were more likely to experience an AMI compared to other age groups (p < 0.001). Autonomic alterations, working habits, and social reasons might contribute to this phenomenon. AF in diabetic patients occurs more frequently at noon (12:00–14:59) (p = 0.019). Conclusions: Diabetic patients with AMI and AF seem to follow a specific circadian pattern in a Mediterranean country, with AMI occurring most often at midnight hours and AF mostly at noon. Autonomic dysfunction, glycemic fluctuations, intense anti-diabetic treatment before lunch, and patterns of insulin secretion and resistance may explain this pattern. More studies are needed to elucidate the circadian pattern of AMI and AF in diabetic patients to contribute to the development of new therapeutic approaches in this setting

Unmet Needs in the Assessment of Right Ventricular Function for Severe Tricuspid Regurgitation

Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease that has been long overlooked, but lately its independent association with adverse cardiovascular outcomes was recognized. The time point to intervene and repair the tricuspid valve is defined by the right ventricular (RV) dilation and dysfunction that comes up at a later stage. While guidelines favor tricuspid valve repair before severe RV dysfunction ensues, the definition of RV dysfunction in a universal manner remains vague. As a result, the candidates for transcatheter or surgical TR procedures are often referred late, when advanced RV dysfunction is established, and any derived procedural survival benefit is attenuated. Thus, it is of paramount importance to establish a universal means of RV function assessment in patients with TR. Conventional echocardiographic indices of RV function routinely applied have fundamental flaws that limit the precise characterization of RV performance. More recently, novel echocardiographic indices such as strain via speckle-tracking have emerged, demonstrating promising results in the identification of early RV damage. Additionally, evidence of the role of alternative imaging modalities such as cardiac computed tomography and cardiac magnetic resonance, for RV functional assessment in TR, has recently arisen. This review provides a systematic appraisal of traditional and novel multimodality indices of RV function in severe TR and aims to refine RV function assessment, designate future directions, and ultimately, to improve the outcome of patients suffering from severe TR

Coagulation Profile of COVID-19 Patients

Coronavirus disease is a viral infection that can affect multiple systems and be expressed with many—or no—symptoms. The viral infection begins when the virus binds to the host’s receptor and from that point on, it is transmitted to the rest of the body, where it causes inflammatory reactions. Among other tissues and systems, SARS-CoV-2 impacts the coagulation system, where it triggers the immunothrombotic response. Its effects are rather intense and can lead to many complications. COVID-19-associated coagulopathy is frequently observed in hospitalized patients, especially ICU patients, and can be proven detrimental. It is usually accompanied by other complications, such as sepsis-induced coagulopathy, disseminated intravascular coagulation and venous thromboembolism. Since all these conditions lead to poor prognosis for severely ill patients, thromboprophylaxis and coagulopathy prognosis are just as important as the therapeutic handling of these patients. Since the beginning of the pandemic, many biomarkers have been considered useful when trying to assess the thrombotic risk of hospitalized patients or evaluate the severity of their situation. At the same time, many drugs have already been tested—while others are still being trialed—in order to find the optimal therapy for each urgent situation

Association of clinical, laboratory and imaging biomarkers with the occurrence of acute myocardial infarction in patients without standard modifiable risk factors – rationale and design of the “Beyond-SMuRFs Study”

Abstract Background Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients. Methods The ‘‘Beyond-SMuRFs Study’’ is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023. Discussion The ‘‘Beyond-SmuRFs’’ study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients’ profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals. Trial Registration ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022