Search

Copyright of Cardiology Letters is the property of Slovak Society of Cardiology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cardio-oncology is a new and fast-evolving collaborative subdiscipline of cardiology whose goal is to increase the quality and length of the lives of oncological patients with precise prophylactic and therapeutical interventions. Novel targeted therapies present a challenge to recognize and treat rare adverse cardiovascular effects, usually without any evidence-based guidance. Therefore, scrupulous descriptions of clinical cases and drafting trials for real-world safety are paramount. We present a case of a 50-year-old Caucasian female who was diagnosed with cancer therapy-related cardiac dysfunction caused by combined BRAF and MEK inhibition in the treatment of malignant melanoma. The patient presented atypically with isolated severe fatigue without other specific cardiovascular symptoms. The findings of echocardiography and cardiac magnetic resonance indicated apical hypertrophic cardiomyopathy (AHCM), which is rare in our region. We stopped the oncological therapy and treated the patient with an ACE inhibitor, a beta-blocker, and an SGLT-2 inhibitor with a satisfactory effect. During the upcoming six months, the patient's state improved, and the control echocardiography ruled out an AHCM. As the patient's state rapidly improved after the withdrawal of BRAF and MEK inhibitors and the morphological finding was reversible, it can be theorized that the cardiotoxicity caused by the aforementioned drugs mimicked the phenotype of AHCM., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Benko et al.)

Aims: The aims of this study were to compare global longitudinal strain of the left ventricle (LV-GLS) and reservoir strain of the left atrium (R-LAS) values between patients with acute decompensation of chronic heart failure (HF) and a control group., Methods: Sixteen patients admitted to our ward for acute decompensation of HF were enrolled in this study. Transthoracic echocardiography (TTE) with two-dimensional speckle-tracking analysis (2D ST) was performed in each patient. The patients were divided into two subgroups according to the value of left ventricular ejection fraction (EF) using a cut-off value of ≤40% to distinguish heart failure with reduced ejection fraction (HFrEF) from heart failure with preserved ejection fraction (HFpEF). The control group consisted of 16 individuals without a history of cardiovascular disease, each of whom underwent 2D ST analysis as well., Results: We found that LV-GLS and R-LAS were significantly lower in both the HFrEF and HFpEF subgroups in comparison with the control group (LV-GLS: -13.4 ± 4.7% vs. -19.7 ± 2.5%, p ˂ 0.05; R-LAS: +12.2 ± 6.9% vs. +40.3 ± 7.4%, p ˂ 0.05). Furthermore, there was a significant difference in LV-GLS (-9.6 ± 3.2% vs. -15.2 ± 4.3%, p ˂ 0.05) but not in R-LAS (+13.7 ± 8.6% vs. +11.4 ± 6.2%) between the HFrEF and HFpEF subgroups., Conclusions: Our study demonstrated a significant difference in LV-GLS and R-LAS in all enrolled HF patients compared to the control group. There was also a significant difference in LV-GLS between the HFrEF and HFpEF subgroups.

Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of VTE, stillbirth, cesarean section and selected thrombophilia. Appropriate thromboprophylaxis has the potential to decrease the risk of VTE in at-risk pregnant patients by 60-70%. Based on this, the authors reviewed the PubMed, Web of Science and Scopus databases to identify the possibilities of thromboprophylaxis in pregnant patients with a high risk of VTE. Moreover, they summarized its management in specific situations, such as cesarean delivery or neuraxial blockade. Currently, low-molecular-weight heparins (LMWH) are the preferred drugs for anticoagulant thromboprophylaxis in the course of pregnancy and postpartum due to easy administration and a lower rate of adverse events.

Platelets are essential in maintaining blood homeostasis and regulating several inflammatory processes. They constantly interact with immune cells, have immunoregulatory functions, and can affect, through immunologically active substances, endothelium, leukocytes, and other immune response components. In reverse, inflammatory and immune processes can activate platelets, which might be significant in autoimmune disease progression and arising complications. Thus, considering this interplay, targeting platelet activity may represent a new approach to treatment of autoimmune diseases. This review aims to highlight the role of platelets in the pathogenic mechanisms of the most frequent chronic autoimmune inflammatory diseases to identify gaps in current knowledge and to provide potential new targets for medical interventions., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Orthotopic heart transplantation is the gold standard for the treatment of advanced heart failure in the absence of contraindications. Infective endocarditis is a rare complication in patients after heart transplantation. The treatment of endocarditis after heart transplantation is challenging since there is a need for ongoing immunosuppression., Case Description: We present the case of a 51-year-old orthotopic heart transplant recipient enrolled in a chronic dialysis program, in whom we diagnosed and successfully treated recurrent infective endocarditis of the mitral valve caused by Enterococcus and Enterobacter species. Despite the complicated course of the disease, the treatment was successful., Conclusions: Recurrent infective endocarditis after heart transplantation can be treated successfully with a multidisciplinary approach and robust antimicrobial therapy., Learning Points: There is a high risk of bacteraemia and subsequent endocarditis in patients with recurrent catheter-related sepsis.The spectrum of bacteria causing endocarditis in patients after heart transplantation differs from that in the general population.Scrupulous targeted antibiotic treatment is warranted for the treatment of immunosuppressed patients with endocarditis., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Transarterial chemoembolization (TACE) is a minimally invasive treatment for liver cancer, often employed as a bridging therapy or destination treatment for non-operable cases. This case report discusses an 82-year-old woman with a large hepatocellular carcinoma (HCC) who underwent elective TACE due to the high surgical risk associated with her tumor size. Unexpectedly, the patient experienced liver rupture 20 h post-procedure, leading to acute surgical intervention. Despite successful hemostasis during surgery, the patient succumbed to progressive multi-organ failure. We aimed to search the PubMed database for documented cases of ruptured HCC after TACE. This study highlights risk factors for spontaneous HCC rupture and specific factors associated with TACE-induced rupture. Transarterial embolization (TAE) is currently favored as the treatment method for spontaneous ruptures, while the optimal therapy for TACE-induced ruptures remains unclear. In conclusion, this case underscores the importance of recognizing the rare complication of HCC rupture post-TACE and the need for personalized risk assessment. While TAE emerges as a primary treatment choice, the lack of consensus necessitates further studies to establish evidence-based approaches for managing this uncommon yet life-threatening complication.

Introduction: Myxoma of the left atrium is a less typical cause of mitral obstruction. If this develops, a flash pulmonary oedema can be the first manifestation., Case Description: We present a case report of a 50-year-old woman who was admitted to our internal department because of dyspnoea. The patient overcame a stroke three years before the index hospitalisation with a negative transthoracic echocardiography. By anamnesis and physical examination, an exacerbation of COPD was assumed, and the patient was treated accordingly. As the patient showed numerous risk factors for heart failure with preserved ejection fraction, transthoracic echocardiography was performed. A large polypoid mass was found in the left atrium, which caused severe mitral obstruction. Subsequent transoesophageal echocardiography confirmed this finding. The patient underwent urgent cardiac surgery, and the tumour was successfully resected. A histological examination revealed a cardiac myxoma. After the cardiac surgery the patient felt well, and no recurrence of the tumour occurred., Conclusions: We provide a case report of a fast-growing myxoma that was incidentally found in a patient with dyspnoea. We highlight the fast growth rate of the tumour and the potential for misdiagnosed signs of pulmonary oedema caused by mitral obstruction., Learning Points: Myxomas are the most common primary tumours of the heart, which can manifest a variety of symptoms such as fever, weight loss, thromboembolism, or mitral obstruction.The symptoms of acute exacerbation of COPD and cardiogenic pulmonary oedema can overlap and can be difficult to differentiate by anamnesis and physical examination alone.Transthoracic echocardiography has a high sensitivity for cardiac masses and is the examination of choice when these are suspected., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC-MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13 C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13 C-labeled adenosine. The 13 C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC-MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine's systemic impact and pave the way for further investigations into its intricate regulatory mechanisms.

Background: Although stroke and acute limb ischemia seem easily distinguishable by anamnesis and physical examination, symptoms may overlap and sometimes mislead the examiner. Such a situation can arise in the occurrence of unilateral neurological symptoms affecting the upper and lower limbs at the same time. As timely diagnosis and a correct therapeutic intervention are crucial to prevent irreversible damage in both diseases, knowledge of the possibility of one disease mimicking the other is essential. We present a unique case of acute unilateral upper and lower limb ischemia mimicking an acute stroke., Case Presentation: A 69-year-old Caucasian patient with known atherosclerotic risk factors was admitted to the emergency department with a suspected stroke with unilateral paresthesia. After a comprehensive examination of the patient with the need for repeated reevaluation and a negative brain computed tomography scan, acute left-sided upper and lower limb ischemia was eventually diagnosed. The patient underwent surgical revascularization of the upper and lower limbs with a satisfactory result and was discharged from the hospital after a few days., Conclusion: It is of utmost importance to always stay alert for stroke mimics, as overlooking can lead to severe complications and delay adequate therapy. Our case shows that persistent diagnostic effort leads to successful treatment of the patient even on rare occasions, as is the acute unilateral upper and lower limb ischemia., (© 2024. The Author(s).)

Objectives: The aim of this article is to provide an insight into the role of obesity as a risk factor, and as a potential etiologic agent of atrial fibrillation (AF) and heart failure (HF)., Methods: A narrative (non-systematic) review article summarizing currently available data regarding the interaction between obesity, AF and HF., Results: Obesity is considered a risk factor of AF and chronic HF. Multiple recent studies indicate that obesity is also a potential causal factor in the development of AF and HF, the elucidation of pathological mechanisms of which could help devise new diagnostic and therapeutic modalities for these conditions. The discussion about obesity in relation to HF cannot omit the so-called obesity paradox, which represents a dilemma for clinicians, and it is still a source of irregularities regarding the strategy of weight reduction in obese patients with HF. Recently, the obesity paradox has also been assumed to play a role in the relationship between obesity and thromboembolic complications of AF., Conclusions: Obesity is an independent and modifiable risk factor for AF and HF. In addition, there is an increasing volume of experimental and clinical data that suggests an important role of the epicardial adipose tissue in the pathophysiology of AF. However, several issues, such as the issue of optimal pharmacotherapy and weight reduction strategy in obese patients with HF remains still unanswered, and open for future investigation., Competing Interests: Conflicts of InterestJakub Jurica, Martin Jozef Péč, Jakub Benko, Tomáš Bolek, Matej Samoš, Peter Galajda, and Marián Mokáň have no conflicts of interest to declare., (© The Author(s) 2023.)

Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endothelial dysfunction, and the resultant clot formation. The main effectors of PCSK9 activation of platelets are CD36 receptors, lipoprotein(a), oxidised LDL particles, tissue factor, and factor VIII. Many more molecules are under investigation, and this area of research is growing rapidly.

The exact incidence of cancer-associated venous thromboembolism (CA-VTE) in patients with oral and facial cancer (OFC) is not exactly known, and this risk is empirically considered to be low. However, this suggestion may result in disease underdiagnosis, prolong the initiation of adequate therapy, and consecutively increase CA-VTE-related morbidity and mortality. In addition, there might be specific clinical problems in the treatment of CA-VTE in patients with oral and facial cancer, such as swallowing difficulties, that might limit the possibilities of oral anticoagulation. Finally, there are limited data regarding the optimal treatment of CA-VTE in patients with oral and facial cancer, and this includes data on novel therapeutic strategies, including the use of direct oral anticoagulants. This article reviews current data on the optimal treatment strategy for CA-VTE in patients with OFC.

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0-1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants., (© 2023 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)

The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates of venous and arterial thrombosis related to COVID-19. The incidence of arterial thrombosis in severe/critically ill intensive care unit-admitted COVID-19 patients appears to be around 1%. There are several ways for the activation of platelets and coagulation that may lead to the formation of thrombi, so it is challenging to make a decision about optimal antithrombotic strategy in patients with COVID-19. This article reviews the current knowledge about the role of antiplatelet therapy in patients with COVID-19.

Patient response to P2Y12 inhibitor therapy is heterogeneous, and those with high on-treatment platelet reactivity (HTPR) are at an increased risk of thrombotic complications. The aim of our study was to determine whether selecting a high-risk patient group of individuals after complex percutaneous coronary intervention (PCI) would show the clinical benefit of HTPR testing for preventing thrombotic complications. Blood samples of patients after complex PCI were acquired 1 day and 1 month after the intervention. The samples were tested using vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) and platelet function assay (PFA). The occurrence of clinically significant stent thrombosis with repeated revascularization of the target vessel was observed over a 1-year period. One day after PCI, 37% of patients had HTPR as established by VASP-P. One month after PCI, the percentage of patients with HTPR decreased to 30.9%. According to PFA, 1 day after PCI, 33.3% of patients had HTPR. This percentage declined to 19.8% after 1 month. All measurements identified a significantly higher proportion of HTPR in patients on clopidogrel compared to ticagrelor and prasugrel. Two cases of early stent thrombosis and 1 case of late stent thrombosis were identified. Further study of adenosine diphosphate receptor blocker on-treatment response in patients undergoing complex PCI is necessary.

Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called "high on-treatment platelet reactivity" or "resistance") could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of "resistance" on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.

Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was <0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients.

Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF.

Myocardial free wall rupture is a rare, but serious complication of acute myocardial infarction with high mortality. We present a case of a 64-year-old patient with this devastating complication of an anterior ST segment elevation myocardial infarction (STEMI) with a prolonged time delay. Cardiac surgery was not performed due to prohibitive surgical risk and predicted poor prognosis. We describe our successful therapeutic intervention consisting of immediate pericardial drainage, vasoactive and inotropic support, intraaortic balloon pump placement and continuous veno-venous hemodialysis. This combined therapy led to patient stabilization and after incremental clinical improvement the patient was able to return to a normal life. After several months a long-term mechanical circulatory support was implanted as a bridge to heart transplant.

Coronavirus disease 2019 (COVID-19) is an acute complex systemic disorder caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).While SARS-CoV-2 is known to cause significant pulmonary disease, various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 is associated with coagulopathy leading to micro and macrovascular complications. Although in patients with COVID-19, venous thromboembolic events are more frequent, arterial thrombosis also occurs at an increased rate. These often lead to acute life-threatening ischemia, which requires urgent diagnosis and treatment. We present case reports of two patients with an abnormal thrombus formation in the thoracic aorta who recently overcame COVID-19, which led to systemic embolism and splenic infarction. Ambulatory oral factor Xa inhibitor therapy led to aortic thrombosis resolution in both patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Alena Strýčková et al.)

Background: It was repeatedly demonstrated that patients with severe COVID-19 pneumonia, as well as patients with type 2 diabetes (T2D) have higher risk of thromboembolic complications. Rotational thromboelastometry (ROTEM®) is a viscoelastic hemostatic assay which allows complex assessment of hemostasis in whole blood. The aim of this study was to compare changes in hemostasis measured by ROTEM® in diabetic and nondiabetic patients with mild COVID-19 pneumonia., Methods: We performed a pilot, prospective, observational study and enrolled 33 consecutive patients (14 with T2D and 19 nondiabetic ones) admitted to regular ward with mild COVID-19 pneumonia. The control group consisted from 11 healthy, nondiabetic blood donors. Blood samples were tested with ROTEM® using INTEM® and EXTEM® reagents., Results: We detected significant differences in EXTEM® clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) comparing patients with mild COVID-19 pneumonia and healthy donors. However, there were no significant differences in EXTEM®, INTEM®, and HEPTEM® parameters (CT, CFT, and MCF) according to diabetes status., Conclusions: Our study demonstrated hypercoagulation in patients with mild COVID-19 pneumonia. T2D did not affected ROTEM® parameters in patients with mild COVID-19 pneumonia., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Massive ileal variceal bleeding is a rare intricate condition that needs rapid management and treatment. The absence of randomized clinical trials in this field leads to a lack of evidence-based diagnostic and therapeutical approaches. We present a case report describing imaging, endoscopic, and surgical procedures leading to the diagnosis and resolution of severe ileal variceal bleeding. Case Report. We admitted a 63-year-old patient for recurrent anemia and ongoing bleeding from the gastrointestinal tract presenting as enterorrhagia. We were not able to elucidate the source by endoscopic, angiographic, or nuclear imaging methods. As a last resort, we carried out a surgical procedure with peroperative enteroscopy and subsequent resection of the affected part of the intestine., Conclusion: We present a patient with a case of ileal variceal bleeding, which required extensive diagnostic and therapeutic effort with a unique peroperative enteroscopic approach., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Marek Cingel et al.)

Background: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke., Patients and Methods: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran)., Results: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001)., Conclusion: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetes is associated with several diabetic-related abnormalities which increase the risk of onset or worsening of heart failure. Recent studies showed that the majority of diabetic patients present with heart failure with preserved ejection fraction (HFpEF), and the prevalence of HFpEF in diabetics is alarming. Moreover, outcomes in HFpEF are poor and could be compared to those of heart failure with reduced ejection fraction (HFrEF), with 1-year mortality ranging between 10 and 30%. In contrast to HFrEF, there is very limited evidence for pharmacologic therapy in symptomatic patients with preserved ejection fraction, and therefore, the optimal selection of treatment for diabetic HFpEF remains challenging. This narrative review article summarizes the currently available data on the pharmacological treatment of HFpEF in patients with diabetes., Competing Interests: Jakub Benko, Matej Samoš, Tomáš Bolek, Dana Prídavková, Jakub Jurica, Martin Jozef Péč, Peter Galajda, and Marián Mokáň have no conflicts of interest to declare, (Copyright © 2022 Jakub Benko et al.)

COVID-19 infection remains a threat to the health systems of many countries. Potential success in the fight against the COVID-19 pandemic is the vaccination of high-risk groups, including patients with end-stage kidney disease (ESKD) and after solid organ transplantation (SOT). Immunosuppression in kidney transplant recipients can also reduce the immunogenicity of SARS-CoV-2 vaccines (varied by vaccine platform), available data suggest that they are efficacious in approximately 50-70%, compared to non-transplant situations. In this paper, we present a newly developed acute humoral and cellular rejection with acute allograft failure and need of hemodialysis 14 days after administration of the adenovirus vectored SARS-CoV-2 vaccine (AstraZeneca; CHADOx1, AZD1222). This occurred in a patient who previously had an asymptomatic COVID-19 infection. Case reports of acute allograft rejection after vaccination against SARS-CoV-2 can help stratify risk groups of patients who develop hyperimmune reactions. However, it is also possible that those with a previous mild primary COVID-19 infection may also develop acute allograft rejections upon COVID-19 re-infection., (© 2022. The Author(s).)

Direct oral anticoagulants (DOACs) are increasingly used worldwide for the prevention of stroke in patients with atrial fibrillation and to prevent or treat venous thromboembolism. In situations such as serious bleeding, the need for urgent surgery/intervention or the management of a thromboembolic event, the laboratory measurement of DOACs levels or anticoagulant activity may be required. Rotational thromboelastometry (ROTEM) is a viscoelastic hemostatic assay (VHA) which has been used in emergencies (trauma and obstetrics), and surgical procedures (cardiac surgery and liver transplants), but experience with this assay in DOACs-treated patients is still limited. This article reviews the use of ROTEM in the setting of DOACs therapy, focusing on DOACs-associated bleeding and the use of this VHA for the management of reversal strategies for DOACs-associated anticoagulation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Apixaban, a direct inhibitor of activated coagulation factor X (FXaI), is being frequently selected for treatment and prevention of venous thromboembolism (VTE). Several reports about possible use of oral FXaI in patients with cancer-associated VTE (CA-VTE) have been published recently., Areas of Uncertainty: The efficacy/safety profile of oral FXaI anticoagulation in patients with CA-VTE seems promising; however, several problems remain unanswered. The pharmacologic profile of apixaban could prefer this agent for the treatment of CA-VTE., Data Sources: Currently available medical literature was searched and reviewed to summarize data regarding the use of apixaban for the prevention and treatment of cancer-associated VTE., Results: Apixaban therapy in patients with cancer and VTE is expected to increase as clinicians gain more experience and reassurance with data from real-world studies that are generally promising. Several studies demonstrated that apixaban exhibits noninferiority to warfarin and low molecular weight heparin in preventing recurrent thrombosis in cancer-associated VTE. Nevertheless, there are still concerns regarding the bleeding associated with apixaban therapy, and regarding the optimal management of these bleeding emergencies., Therapeutic Opinion: Although currently available evidence confirms the noninferiority of apixaban for reduction of the risk of recurrent VTE in patients with cancer; there are still concerns regarding the safety, especially in selected subpopulations of these patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Atorvastatin and direct oral factor Xa inhibitors (xabans) are frequently co-administrated in patients with atrial fibrillation (AF). However, no studies investigating the possibility of the pharmacologic interaction between these agents have been conducted. The aim of this prospective observational study was to determine the impact of atorvastatin therapy on anti-Xa activity in xabans-treated patients with AF. We enrolled 115 AF patients on long-term rivaroxaban (52 patients) and long-term apixaban (63 patients) therapy. Long-term atorvastatin (40 mg once daily) was administrated to 28 rivaroxaban-treated patients and to 28 apixaban-treated patients. Trough and peak samples were tested for anti-Xa activity with drug-specific anti-Xa chromogenic analysis. For rivaroxaban, there were no significant differences in trough activity (45.5 ± 39.5 ng/ml vs. 46.2 ± 30.1 ng/ml; p = .34) and peak anti-Xa activity (179.2 ± 108.8 ng/ml vs. 208.1 ± 104.1 ng/ml; p = .94) between atorvastatin-treated patients and those without atorvastatin. Similarly, atorvastatin did not impact the trough activity (127.7 ± 71.1 ng/ml vs. 100.8 ± 61.1 ng/ml; p = .12) or peak anti-Xa activity (213.8 ± 103.6 ng/ml vs. 179.3 ± 72.9 ng/ml; p = .14) among apixaban-treated patients with AF. This observational study did not show a significant impact of atorvastatin on trough and peak anti-Xa activity in xabans-treated patients with AF., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Platelets play crucial role in acute vascular atherosclerotic diseases, including myocardial infarction and stroke. Additionally, platelet aggregation is a key target of antiplatelet agents, forming the keystone of pharmacotherapy of various atherosclerotic cardiovascular diseases. Thromboelastography and thromboelastometry, representing currently available viscoelastic hemostatic assays (VHA), are designed as whole blood, real-time analyzers of clot formation and clot resolution. These assays could, in theory, overcome some limitations of currently available platelet function testing assays. This article reviews the current experience with the use of VHA for platelet function testing and for monitoring of the response to antiplatelet therapy.

Background: Insulinomas are the most common type of functioning endocrine neoplasms of the pancreas presenting hypoglycemic symptoms. Patients characteristically develop symptoms while fasting, but some patients have reported symptoms only in the postprandial state. Repeated and prolonged hypoglycemic episodes can reduce the awareness of adrenergic symptoms, and patients may have amnesia, which delays diagnosis., Case Summary: We describe a case of a 24-year-old underweight patient who showed hypoglycemic symptoms for almost 6 years. Although patients with insulinoma characteristically develop symptoms while fasting, this young man had hypoglycemic symptoms up to one hour postprandially, especially after high-sugar meals and after physical activity. The fasting tests and imaging methods performed at local hospitals were evaluated as negative for abnormal results. However, brown adipose tissue exhibited increased metabolic activity, and some muscle groups had histological changes as indicated by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography. Glycogen deficiency was also histologically confirmed. The patient's symptoms progressed over the years and occurred more frequently, i.e ., several times a month, and the patient had reduced awareness of adrenergic symptoms. The follow-up fasting test was positive, and the imaging results showed a tumor in the head of the pancreas. The patient underwent laparotomy with enucleation of the insulinoma., Conclusion: Weight gain and fasting hypoglycemia are not necessarily characteristics of insulinoma. In prolonged cases, adrenergic symptoms can be suppressed., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Several studies demonstrated that proton pump inhibitors (PPIs) co-administrated with dabigatran in patients with atrial fibrillation (AF) decreased dabigatran trough and peak plasma levels. However, it is still unknown whether this interaction is reversible or not, and whether the withdrawal of PPI would lead to normalization of dabigatran plasma levels., Aim of Study: The aim of this study was to determine the effect of PPI withdrawal on dabigatran plasma levels in patients with AF., Methods: This pilot prospective study enrolled 23 AF patients on long-term dabigatran and PPI therapy (omeprazole 20 mg twice daily or pantoprazole 40 mg once daily). Dabigatran trough and peak levels (ng/mL) were tested on PPI and after a 2-week period of PPI withdrawal with Hemoclot Thrombin Inhibitor Assay., Results: The analysis of dabigatran plasma levels demonstrated significant elevation in trough dabigatran levels after 2 weeks of PPI withdrawal (97.2 ± 79.7 vs. 163.8 ± 105.5 ng/mL; P < 0.05). Moreover, significantly higher peak dabigatran levels were observed after 2 weeks of PPI withdrawal (142.4 ± 102.8 vs. 255 ± 129.5 ng/mL; P ≤ 0.001)., Conclusions: This study showed that a 2-week period of PPI withdrawal lead to a significant increase in dabigatran trough and peak plasma levels in patients with AF.

Type 2 diabetes (T2D) is an independent risk factor of stroke and systemic embolism in patients with atrial fibrillation (AF), and T2D patients with AF-associated stroke seem to have worse clinical outcome and higher risk of unfavorable clinical course compared to individuals without this metabolic disorder. Long-term anticoagulation is indicated in majority of T2D patients with AF to prevent adverse AF-associated embolic events. Direct oral anticoagulants (DOACs), direct oral thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have emerged as a preferred choice for long-term prevention of stroke in AF patients offering potent and predictable anticoagulation and a favorable pharmacology with low risk of interactions. This article reviews the current data regarding the use of DOACs in individuals with T2D and AF., Competing Interests: Dana Prídavková, Matej Samoš, Tomáš Bolek, Ingrid Škorňová, Jana Žolková, Peter Kubisz, Ján Staško, and Marián Mokáň have no conflicts of interest to declare., (Copyright © 2019 Dana Prídavková et al.)

Dabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels., Competing Interests: The authors have no conflict of interest to declare., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Very limited but promising experiences with the use of direct factor Xa inhibitors for the treatment of heparin-induced thrombocytopenia (HIT) have been reported. This contribution features our first experience with the use of apixaban (without a pre-treatment with parenteral anticoagulant) to treat a case of HIT which developed in a patient after multiple heart replacement surgery. Apixaban was effective, well tolerated and safe. An apixaban-calibrated chromogenic anti-Xa activity assessment was used to monitor apixaban activity throughout the therapy. Patient continued on apixaban for the prevention of thrombosis in the settings of atrial fibrillation. No ischemic or bleeding events occurred during the clinical follow up and the platelet count was stable. Our experience suggests that apixaban might be effectively used for the treatment of HIT and for the long-term prevention of embolism in patients after multiple valve replacement with biological prostheses and atrial fibrillation.

Venous thromboembolism (VTE) is a rare, but life-threatening disease in those who have not reached their adulthood. This condition is usually treated with heparin or low molecular weight heparins which require parenteral administration and, in case of unfractionated heparin, also frequent laboratory monitoring and dose adjustment. Direct oral anticoagulants (DOACs)-direct thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors rivaroxaban, apixaban, and edoxaban-are currently frequently used for the prevention and treatment of VTE in adult population. In fact, these agents offer several advantages compared to traditional agents, such as oral route of administration, short on-set and off-set of action, predictable pharmacologic profile with low risk of food and drug interactions, and no need for routine laboratory assessment of anticoagulant activity. However, clinical experience with these directly acting oral anticoagulants in pediatric population is very limited as these drugs had been tested and are used mostly in adult individuals. This article reviews the current data from pre- and post-marketing studies reporting the use of DOACs for the treatment of VTE in pediatric patients.

Introduction: The role of hypoglycemia in cardiovascular disease still needs to be evaluated. Incidental case studies provide direct, but so far limited, evidence for the direct impairment of heart caused by hypoglycemia. We present a case of severe hypoglycemia manifesting with acute ST elevation myocardial infarction (STEMI)., Case Presentation: A 48-year old man committed a suicidal attempt by insulin self-injection. The emerged hypoglycemia was accompanied by ECG changes and positive troponins confirming the diagnosis of STEMI. Urgent coronary angiography was performed, but no acute coronary artery closure/critical stenosis was found. After resolution of hypoglycemia all signs of ischemia diminished. Insulin and C-peptide levels confirmed exogenous hyperinsulinemia, confirming insulin self-injection. Sadly, the patient suffered irreversible brain damage., Conclusion: This patient case shows that severe hypoglycemia can precipitate acute STEMI., Competing Interests: Conflict of interestJakub Benko, Tomáš Bolek, Dana Prídavková, Peter Galajda, Matej Samoš, and Marián Mokáň declare that they have no conflicts of interest that might be relevant to the contents of this manuscript., (© Springer Nature Switzerland AG 2019.)

Background: Proton pump inhibition (PPI) administrated together with dabigatran reduces the risk of gastrointestinal hemorrhage. However, there is a discussion regarding possible PPI-dabigatran interaction that may reduce the efficacy of this therapy., Study Question: To determine the impact of concomitant PPI on dabigatran plasma levels in patients with nonvalvular atrial fibrillation (NV-AF)., Study Design: A pilot prospective study in patients with NV-AF on dabigatran therapy was performed; 31 patients were enrolled. PPI with either omeprazole or pantoprazole was administrated in 19 patients., Measures and Outcomes: Blood samples were taken for the assessment of the dabigatran trough and peak levels. Dabigatran concentration was measured with the Hemoclot Thrombin Inhibitor Assay., Results: There were significant differences in dabigatran trough level comparing patients treated with PPI and patients without PPI (58.86 ± 36.76 ng/mL vs. 110.72 ± 88.47 ng/mL, P < 0.05). Similarly, there were significant differences in dabigatran peak level between compared groups (88.0 ± 20.5 ng/mL vs. 174.4 ± 139.64 ng/mL, P < 0.05)., Conclusions: This pilot study demonstrated the interaction between PPI and dabigatran levels in patients with NV-AF.