Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

BACKGROUND: Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF). METHODS: We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale. RESULTS: A total of 11 studies were eligible for final analysis (n = 1481 patients with HF). The studies were segregated into 3 groups: (1) the evaluation of patients presenting to the emergency department with dyspnea, (2) the evaluation of patients presenting to the HF clinic for follow-up, and (3) the evaluation of hospitalized patients with acutely decompensated HF or undergoing right heart catheterization. US parameters included IJV height, IJV diameter, IJV diameter ratio, IJV cross-sectional area, respiratory compressibility index, and compression compressibility index. CONCLUSIONS: The findings of this systematic review suggest a significant role for ultrasound interrogation of the IJV in evaluation of patients in the emergency department presenting with dyspnea, in the outpatient clinic for poor clinical outcomes in HF, and in determining the timing of discharge for patients admitted with acutely decompensated HF. Further studies are warranted for testing the reliability of the reported ultrasound indices.

Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction.

INTRODUCTION: Achieving reperfusion immediately after acute myocardial infarction improves outcomes; despite this, patients remain at a high risk for mortality and morbidity at least for the first year after the event. Ischemia-reperfusion injury (IRI) has a complex pathophysiology and plays an important role in myocardial tissue injury, repair, and remodeling. AREAS COVERED: In this review, the authors discuss the various mechanisms and their pharmacological agents currently available for reducing myocardial ischemia-reperfusion injury (IRI). They review important original investigations and trials in various clinical databases for treatments targeting IRI. EXPERT OPINION: Encouraging results observed in many preclinical studies failed to show similar success in attenuating myocardial IRI in large-scale clinical trials. Identification of critical risk factors for IRI and targeting them individually rather than one size fits all approach should be the major focus of future research. Various newer therapies like tocilizumab, anakinra, colchicine, revacept, and therapies targeting the reperfusion injury salvage kinase pathway, survivor activating factor enhancement, mitochondrial pathways, and angiopoietin-like peptide 4 hold promise for the future.

Synergistic influence of rivaroxaban on inflammation and coagulation biomarkers in patients with coronary artery disease and peripheral artery disease on aspirin therapy.

COMPASS study demonstrated efficacy of dual pathway inhibition with 2.5 mg twice daily rivaroxaban and aspirin in patients with polyvascular disease (coronary artery disease, peripheral arterial disease or both), the underlying mechanism of which is not clearly understood. In this Phase IV, prospective, open-label and randomized study, we hypothesize that treatment with rivaroxaban is associated with a reduction in platelet activation and aggregation, inflammation and coagulation markers. 30 patients will be randomly treated with aspirin (81 mg q.d.) or aspirin plus rivaroxaban (2.5 mg b.i.d.) for 12 weeks. Platelet aggregation, platelet activation and inflammation markers, thrombin generation kinetics and tissue factor-induced platelet-fibrin clot strength will be measured at baseline, and 4 and 12 weeks after randomization. Trial registration number: NCT04059679.

Direct oral anticoagulants: a review on the current role and scope of reversal agents.

New guideline recommendations prefer direct oral anticoagulants (DOACs) over warfarin in DOAC-eligible patients with atrial fibrillation and patients with venous thromboembolism. As expected with all antithrombotic agents, there is an associated increased risk of bleeding complications in patients receiving DOACs that can be attributed to the DOAC itself, or other issues such as acute trauma, invasive procedures, or underlying comorbidities. For the majority of severe bleeding events, the widespread approach is to withdraw the DOAC, then provide supportive measures and "watchful waiting" with the expectation that the bleeding event will resolve with time. However, urgent reversal of anticoagulation may be advantageous in patients with serious or life-threatening bleeding or in those requiring urgent surgery or procedures. Until recently, the lack of specific reversal agents, has affected the uptake of these agents in clinical practice despite a safer profile compared to warfarin in clinical trials. In cases of life-threatening or uncontrolled bleeding or when patients require emergency surgery or urgent procedures, idarucizumab has been recently approved for reversal of anticoagulation in dabigatran-treated patients and andexanet alfa for factor Xa inhibitor-treated treated patients. The current review summarizes the current clinical evidence and scope of these agents with the potential impact on DOAC use in clinical practice.

Investigational drugs in phase II clinical trials for acute coronary syndromes.

Introduction: Despite current guideline-based, secondary prevention strategies in patients with the acute coronary syndrome, the residual ischemic risk is still at an unacceptable rate, and there is a concomitant high bleeding event rate. These observations mandate investigations of novel treatment strategies to meet the unmet need to improve outcomes in patients with ACS.Areas covered: In this review, the author(s) focus on new agents with ongoing or recently completed phase II trials for the treatment of ACS. We searched MEDLINE and clinicaltrials.org for Phase II trials in ACS patients, and important original investigations are reviewed.Expert opinion: Some of the novel drugs evaluated in the Phase II trials hold promise for future therapies such as AZD5718, anakinra, tocilizumab, CSL112, MEDI 6102, inclisiran, PZ128, selatogrel, and RVX-208. Their efficacy and safety should be evaluated in large scale Phase III trials. The higher cost of the drug will be a major limitation for wide-spread use of novel agents in general practice in future.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL ß2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

HDL3-C is a Marker of Coronary Artery Disease Severity and Inflammation in Patients on Statin Therapy.

INTRODUCTION: Low high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL2-C and HDL3-C for assessing CAD severity in patients on statin therapy. METHODS: Blood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were analyzed. CAD severity was angiographically defined as severe CAD (>75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD. RESULTS: Patients with severe CAD had a significantly lower total-HDL-C, lower HDL3-C and higher lipoprotein(a) levels. HDL3-C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL3-C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL were found to have significantly elevated ox-LDL levels. CONCLUSION: In patients on statin therapy, HDL3-C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL have greater inflammation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity.