Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial.

BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. OBJECTIVES: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.

N-terminal prohormone of brain natriuretic peptide in gestational hypertension and preeclampsia - State of the art.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these patients.

Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a).

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% - 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8-54.7); p = 0.005], 42.6% [(29.7-54.1); p = 0.030] and 26.7% [(1.0-62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.

Coagulation Disorders and Thrombotic Complications in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with multiple cardiovascular and noncardiovascular comorbidities and risk factors which increase the risk of thrombotic complications, such as atrial fibrillation, chronic kidney disease, arterial hypertension and type 2 diabetes mellitus. Subsequently, thromboembolic risk stratification in this population poses a great challenge. Since date from the large randomized clinical trials mostly include both patients with truly preserved EF, and those with heart failure with mildly reduced ejection fraction, there is an unmet need to characterize the patients with truly preserved EF. Considering the significant evidence gap in this area, we sought to describe the coagulation disorders and thrombotic complications in patients with HFpEF and discuss the specific thromboembolic risk factors in patients with HFpEF, with the goal to tailor risk stratification to an individual patient.

STRUGGLE FOR. Italian-Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023 for better control of classical modifiable risk factors in clinical practice.

The progress in pharmacotherapy that has been made in recent years, including the introduction of very effective and safe lipid-lowering and antihypertensive drugs, has not yet translated into the expected universal control of blood pressure, lipid disorders and diabetes. In the STRUGGLE FOR Italian- -Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023, experts from five countries recounted several points about the paradigms of cardiological and cardiometabolic care for better control of classical modifiable risk factors in the year 2023. It is believed herein, that the need to intensify treatment, actively search for patients with cardiovascular risk factors, especially with arterial hypertension, hypercholesterolemia and diabetes, should go hand in hand with the implementation of the latest therapy, based on single pill combinations including proven, effective antihypertensive, lipid-lowering and antidiabetic molecules, many of which are listed in the present document. There is a need to use both new technological concepts, completely new drugs, as well as novel treatment concepts such as metabolic treatment in coronary artery disease, try to intensify the fight against smoking in every way, including the available range of drugs and procedures reducing the harm. This approach will provide substantially better control of the underlying cardiovascular risk factors in countries as varied as Italy, Poland, Spain, Uzbekistan and Vietnam.

The Ketogenic Effect of SGLT-2 Inhibitors-Beneficial or Harmful?

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.

Multicenter registry of Impella-assisted high-risk percutaneous coronary interventions and cardiogenic shock in Poland (IMPELLA-PL).

BACKGROUND: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021. AIMS: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries. METHODS: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge. RESULTS: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively. CONCLUSIONS: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation.

MicroRNAs in Myocarditis-Review of the Preclinical In Vivo Trials.

Myocarditis is an inflammatory heart disease with viruses as the most common cause. Regardless of multiple studies that have recently been conducted, the diagnostic options still need to be improved. Although endomyocardial biopsy is known as a diagnostic gold standard, it is invasive and, thus, only sometimes performed. Novel techniques of cardiac magnetic resonance are not readily available. Therapy in viral infections is based mainly on symptomatic treatment, while steroids and intravenous immunoglobulins are used in autoimmune myocarditis. The effectiveness of neither of these methods has been explicitly proven to date. Therefore, novel diagnostic and therapeutic strategies are highly needed. MiRNAs are small, non-coding molecules that regulate fundamental cell functions, including differentiation, metabolism, and apoptosis. They present altered levels in different diseases, including myocarditis. Numerous studies investigating the role of miRNAs in myocarditis have already been conducted. In this review, we discussed only the original preclinical in vivo research. We eventually included 30 studies relevant to the discussed area. The altered miRNA levels have been observed, including upregulation and downregulation of different miRNAs in the mice models of myocarditis. Furthermore, the administration of mimics or inhibitors of particular miRNAs was shown to significantly influence inflammation, morphology, and function of the heart and overall survival. Finally, some studies presented prospective advantages in vaccine development.

Long-term mortality after transcatheter aortic valve implantation for aortic stenosis in immunosuppression-treated patients: a propensity-matched multicentre retrospective registry-based analysis.

Introduction: Data regarding patients with a previous medical record of immunosuppression treatment who have undergone transcatheter aortic valve implantation (TAVI) are limited and extremely inconclusive. Available studies are mostly short term observations; thus there is a lack of evidence on efficacy and safety of TAVI in this specific group of patients. Aim: To compare the in-hospital and long-term outcomes between patients with or without a medical history of immunosuppressive treatment undergoing TAVI for aortic valve stenosis (AS). Material and methods: We conducted a retrospective registry-based analysis including patients undergoing TAVI for AS at 5 centres between January 2009 and August 2017. The primary endpoint was long-term all-cause mortality. Secondary endpoints comprised major vascular complications, life-threatening or disabling bleeding, stroke and new pacemaker implantation. Results: Of 1451 consecutive patients who underwent TAVI, two propensity-matched groups including 25 patients with a history of immunosuppression and 75 patients without it were analysed. No differences between groups in all-cause mortality were found in a median follow-up time of 2.7 years following TAVI (p = 0.465; HR = 0.73; 95% CI: 0.30-1.77). The rate of major vascular complications (4.0% vs. 5.3%) was similar in the two groups (p = 1.000). There were no statistically significant differences in the composite endpoint combining life-threatening or disabling bleeding, major vascular complications, stroke and new pacemaker implantation (40.0% vs. 20.0%, p = 0.218). Conclusions: Patients who had undergone TAVI for AS had similar long-term mortality regardless of whether they had a previous medical record of immunosuppression. Procedural complication rates were comparable between the groups.

The Role of MicroRNAs in Aortic Stenosis-Lessons from Recent Clinical Research Studies.

Aortic stenosis (AS) is the most prevalent primary valve lesion demanding intervention. Two main treatment options are surgical aortic valve replacement or transcatheter aortic valve implantation. There is an unmet need for biomarkers that could predict treatment outcomes and become a helpful tool in guiding Heart Team in the decision-making process. Micro-ribonucleic acids (microRNAs/miRs) have emerged as potential biomarkers thoroughly studied in recent years. In this review, we aimed to summarize the current knowledge about the role of miRNAs in AS based on human subject research. Much research investigating miRNAs' role in AS has been conducted so far. We included 32 original human subject research relevant to the discussed field. Most of the presented miRNAs were studied only by a single research group. Nevertheless, several miRNAs appeared more than once, sometimes with high consistency between different studies but sometimes with apparent discrepancies. The molecular aspects of diseases are doubtlessly exciting and provide invaluable insights into the pathophysiology. Nevertheless, translating these findings, regarding biomarkers such as miRNAs, into clinical practice requires much effort, time, and further research with a focus on validating existing evidence.

Diagnostic value of soluble urokinase-type plasminogen activator receptor in patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS. METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed. RESULTS: Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001). CONCLUSIONS: In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.

The role of galectin-3 in atrial fibrillation.

Numerous risk factors for atrial fibrillation (AF) progression have been identified. However, the biomarkers mentioned in the guidelines do not have any clinically relevant predictive value. Some research groups investigated the potential utility of galectin-3 (gal-3) as a diagnostic, prognostic, and predictive biomarker in AF. In this review, we have thoroughly summarized the current data on the role of gal-3 in AF based on the original research in this field. Patients suffering from AF present with increased levels of gal-3. The concentration of gal-3 differs between patients with AF depending on the type of AF - it is higher in patients with persistent AF than in patients with paroxysmal AF. Multiple studies investigating the reappearance of AF in patients who underwent ablation have shown that gal-3 is a promising biomarker to predict the outcome of this therapy. Patients with increased levels of gal-3 are at higher risk of AF recurrence. Although the research considered in this work addressed many aspects of the role of gal-3 in AF, most of it has been conducted on a small group of patients. Therefore, further research and extensive clinical trials confirming described findings are highly warranted.

Nanoparticles: a breakthrough in COVID-19 prevention, diagnosis and treatment.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared a global pandemic by the World Health Organization (WHO). The three key principles in management of the COVID-19 pandemic are prevention, early detection and targeted treatment. Vaccine-based prevention together with early detection has already proven its efficacy in controlling the pandemic. Early detection of infected patients could substantially accelerate the implementation of treatment, but also help to identify infection hotspots, whereas targeted treatment might destroy the virus and minimize damage to healthy tissue. Nanoparticles hold great promise with respect to these aspects. They may also be the solution to emerging clinical problems such as reinfection, pregnancy-related COVID-19 and coinfection. Here, we aim to discuss the potential applications of nanoparticles to combat the COVID-19 pandemic.

Extracellular Vesicles in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Despite recent progress in the diagnosis and treatment of CAD, evidence gaps remain, including pathogenesis, the most efficient diagnostic strategy, prognosis of individual patients, monitoring of therapy, and novel therapeutic strategies. These gaps could all be filled by developing novel, minimally invasive, blood-based biomarkers. Potentially, extracellular vesicles (EVs) could fill such gaps. EVs are lipid membrane particles released from cells into blood and other body fluids. Because the concentration, composition, and functions of EVs change during disease, and because all cell types involved in the development and progression of CAD release EVs, currently available guidelines potentially enable reliable and reproducible measurements of EVs in clinical trials, offering a wide range of opportunities. In this chapter, we provide an overview of the associations reported between EVs and CAD, including (1) the role of EVs in CAD pathogenesis, (2) EVs as biomarkers to diagnose CAD, predict prognosis, and monitor therapy in individual patients, and (3) EVs as new therapeutic targets and/or drug delivery vehicles. In addition, we summarize the challenges encountered in EV isolation and detection, and the lack of standardization, which has hampered real clinical applications of EVs. Since most conclusions are based on animal models and single-center studies, the knowledge and insights into the roles and opportunities of EVs as biomarkers in CAD are still changing, and therefore, the content of this chapter should be seen as a snapshot in time rather than a final and complete compendium of knowledge on EVs in CAD.