The role of direct oral anticoagulants in the era of COVID-19: are antiviral therapy and pharmacogenetics limiting factors?

In patients with COVID-19, thromboinflammation is one of the main causes of morbidity and mortality, which makes anticoagulation an integral part of treatment. However, pharmacodynamic and pharmacokinetic properties of direct oral anticoagulants (DOACs) limit the use of this class of anticoagulants in COVID-19 patients due to a significant interference with antiviral agents. DOACs use in COVID-19 hospitalized patients is currently not recommended. Furthermore, patients already on oral anticoagulant drugs should be switched to heparin at hospital admission. Nevertheless, outpatients with a confirmed diagnosis of COVID-19 are recommended to continue prior DOAC therapy. More studies are required to clarify the pathogenesis of COVID-19-induced derangement of the coagulation system in order to recommend an appropriate anticoagulant treatment.

The N-Glycosylation of Total Plasma Proteins and IgG in Atrial Fibrillation.

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA2DS2-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation.

Relationship of genetic markers for atherosclerosis and long-term outcome after percutaneous coronary intervention with stenting.

The aim of the study was to describe the relationship of clinical outcome after percutaneous coronary intervention (PCI) with stenting and genetic polymorphisms (GP) which are known to relate to the incidence of in-stent restenosis and late thrombotic complications. The study included 190 patients with standardized clinical follow-up over 5 years, which were initially treated with PCI. We investigated clinical data, angiographic characteristics, 10 polymorphisms involved in neointimal hyperplasia and late thrombosis at 6 different levels and their relationship with the major adverse cardiac events (MACE). The long-term clinical outcome was defined by MACE: death, target vessel revascularization (PCI or coronary bypass grafting, CABG) and myocardial infarction. Angiotensin receptor type I (AGTR A1166C) and angiotensinogen (AGT MET235THR) GPs correlated with repeat revascularization and total MACE. Carriers of G allele for NOS3 A922G GP were shown to have a significantly lower repeat revascularization rate in comparison with the AA genotype, as did the T allele carriers in the NOS3 C690T GP analysis when compared to the CC genotype. The Asp genome carriers with the NOS3 GLU298ASP GP were also shown to have significantly less re-PCI in contrast to the Glu/Glu genotype. The study could document the protective influence of the 4G/5G GP for plasminogen inhibitor activator-1, which carried the lowest rate of re-PCI and total MACE during the follow-up. GPs for beta-1 G-protein subunit GNB3 C825T, fibrinogen FGB G455A and E-selectins Ser128Arg and Leu554Phe did not show statistical correlation with the clinical outcome. The results illustrate the potential use of genetic markers in defining patients with possibly worse clinical outcome after PCI, who may profit from more aggressive prevention of restenosis and late thrombotic complications.

Angiographic control and percutaneous treatment of myocardial ischemia immediately after CABG.

Perioperative myocardial ischemia is rare but serious complication of CABG. Graft dysfunction, coronary artery thrombosis and incomplete revascularization are main causes. Pharmacological treatment, intra aortic counter pulsation and immediate additional grafting have limited results. Treatment strategy based on coronary angiography findings could lessen the burden of high mortality rate in these patients. The purpose of this study was to analyze the causes of perioperative ischemia and angiography based treatment strategy including percutaneous intervention. We enrolled all 55 consecutive patients that went early coronary angiography for perioperative myocardial ischemia in a prospective longitudinal study. Incorrect graft anastomosis, graft spasm, displacement and dissection were found in 49%, 7%, 5% and 4% of patients, respectively. Acute coronary artery thrombotic occlusion was found in 5% of patients and ischemia due to incomplete revascularization in 6% of patients. In 22% of patients no cause of myocardial ischemia could be detected. There were no complications of coronary angiography. Based on coronary angiography findings percutaneous intervention was performed in 30 patients, additional grafting in 8 patients and no action was taken in 17 patients. Percutaneous intervention with stenting was performed on coronary arteries (78%) and graft anastomosis (22%) with primary success 97%. One anastomosis rupture with treatable tamponade and one lethal stent thrombosis were complications of percutaneous treatment. Overall in hospital mortality was 30%. We concluded that graft dysfunction is usual cause of myocardial ischemia due to incorrect anastomosis and that percutaneous intervention on bypass graft or coronary artery can lessen high mortality rate in these patients.

Is the extent of left atrial fibrosis associated with body mass index in patients undergoing pulmonary vein isolation for atrial fibrillation?

BACKGROUND: Left atrial (LA) fibrosis is associated with a higher rate of recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI). Body mass index (BMI) is strongly associated with the prevalence of AF, but there is insufficient data about the association between BMI and LA fibrosis. AIMS: The aim of the study was to examine the association between LA fibrosis and BMI in patients with AF undergoing PVI. METHODS: In 114 patients an electro-anatomical voltage map was created using the CARTO 3 three-dimensional system before PVI. The total fibrosis area (voltage criteria ≤0.5 mV), percentage, and the number of fibrotic areas were calculated. A general linear model was used to determine the differences in BMI with confounders between groups of patients with differing extents of fibrosis and numbers of focuses. RESULTS: Advanced fibrosis was found in 53 (47%) patients, in up to 9 areas with a median of 2 and an interquartile range (IQR) of 0-3. The median total fibrotic area was 27.3 cm2 with an IQR of 0.1-30.3 cm2. Patients were stratified by percentage of fibrotic area: <5%, 5%-20%, 20%-35%, and above 35%; no significant difference in mean BMI was found between the groups (P = 0.57). When stratified by the number of fibrotic areas (0, 1, 2, and ≥3 fibrotic areas), no difference in BMI was noted between the groups (P = 0.67). CONCLUSIONS: Fibrosis of the LA, as the strongest predictor of AF recurrence after PVI, does not correlate with BMI in patients with AF where PVI is indicated.