Oral anticoagulation therapy in atrial fibrillation patients at high risk of bleeding: Clinical characteristics and treatment strategies based on data from the Polish multicenter register of atrial fibrillation (POL-AF).

BACKGROUND: Despite its benefits, oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF) is associated with hemorrhagic complications. AIMS: We aimed to evaluate clinical characteristics of AF patients at high risk of bleeding and the frequency of OAC use as well as identify factors that predict nonuse of OACs in these patients. METHODS: Consecutive AF patients hospitalized for urgent or planned reasons in cardiac centers were prospectively included in the registry in 2019. Patients with HAS-BLED ≥3 (high HAS-BLED group) were assumed to have a high risk of bleeding. RESULTS: Among 3598 patients enrolled in the study, 29.2% were at high risk of bleeding (44.7% female; median [Q1-Q3] age 72 [65-81], CHA2DS2-VASc score 5 [4-6], HAS-BLED 3 [3-4]). In this group, 14.5% of patients did not receive OACs, 68% received NOACs, and 17.5% VKAs. In multivariable analysis, the independent predictors of nonuse of oral OACs were as follows: creatinine level (odds ratio [OR], 1.441; 95% confidence interval [CI], 1.174-1.768; P <0.001), a history of gastrointestinal bleeding (OR, 2.918; 95% CI, 1.395-6.103; P = 0.004), malignant neoplasm (OR, 3.127; 95% CI, 1.332-7.343; P = 0.009), and a history of strokes or transient ischemic attacks (OR, 0.327; 95% CI, 0.166-0.642; P = 0.001). CONCLUSIONS: OACs were used much less frequently in the group with a high HAS-BLED score than in the group with a low score. Independent predictors of nonuse of OACs were creatinine levels, a history of gastrointestinal bleeding, and malignant neoplasms. A history of stroke or transient ischemic attack increased the chances of receiving therapy.

Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER): protocol for a prospective observational nationwide study.

INTRODUCTION: Atrial fibrillation (AF) is a prevalent disease considerably contributing to the worldwide cardiovascular burden. For patients at high thromboembolic risk (CHA2DS2-VASc ≥3) and not suitable for chronic oral anticoagulation, owing to history of major bleeding or other contraindications, left atrial appendage occlusion (LAAO) is indicated for stroke prevention, as it lowers patient's ischaemic burden without augmentation in their anticoagulation profile. METHODS AND ANALYSIS: Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER) will be conducted in 10 heart surgery and cardiology centres across Poland to assess the outcomes of LAAO performed by fully thoracoscopic-epicardial, percutaneous-endocardial or hybrid endo-epicardial approach. The registry will include patients with nonvalvular AF at a high risk of thromboembolic and bleeding complications (CHA2DS2-VASc Score ≥2 for males, ≥3 for females, HASBLED score ≥2) referred for LAAO. The first primary outcome is composite procedure-related complications, all-cause death or major bleeding at 12 months. The second primary outcome is a composite of ischaemic stroke or systemic embolism at 12 months. The third primary outcome is the device-specific success assessed by an independent core laboratory at 3-6 weeks. The quality of life (QoL) will be assessed as well based on the QoL EQ-5D-5L questionnaire. Medication and drug adherence will be assessed as well. ETHICS AND DISSEMINATION: Before enrolment, a detailed explanation is provided by the investigator and patients are given time to make an informed decision. The patient's data will be protected according to the requirements of Polish law, General Data Protection Regulation (GDPR) and hospital Standard Operating Procedures. The study will be conducted in accordance with the Declaration of Helsinki. Ethical approval was granted by the local Bioethics Committee of the Upper-Silesian Medical Centre of the Silesian Medical University in Katowice (decision number KNW/0022/KB/284/19). The results will be published in peer-reviewed journals and presented during national and international conferences. TRIAL REGISTRATION NUMBER: NCT05144958.

Phenotyping in heart failure with preserved ejection fraction: A key to find effective treatment.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly widespread medical condition, with excessive morbidity and mortality. Recently, for the first time in HFpEF, a reduction in the primary composite outcome of cardiovascular death or HF hospitalization was shown with empagliflozin. The failure of previous clinical trials in HFpEF might have resulted from suboptimal patient selection and inclusion of patients without "true" or clinically significant HFpEF. Another important factor might be the heterogeneity of HFpEF, and thus there is a growing interest in HFpEF phenotyping. This phenotyping can be based on clinical presentation (e.g., subtypes with predominant atrial fibrillation, obesity, pulmonary hypertension and right ventricular failure, coronary artery disease (CAD), or noncardiac comorbidities), but also on HFpEF etiology. Specific therapies, such as tafamidis in transthyretin-related amyloidosis (ATTR) or mavacamten in hypertrophic cardiomyopathy, have demonstrated their efficacy. However, pathomechanisms leading to the development of different phenotypes of HFpEF seem more complex and subtle. Machine learning and neural network models might help identify specific subgroups within the HFpEF population that either cluster patients with similar genetic, biochemical, echocardiographic or clinical characteristics, or respond similarly to a given treatment. Herein, we review different approaches to HFpEF phenotyping and present some distinct HFpEF subtypes.

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice.

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients.

Why Did All Patients with Atrial Fibrillation and High Risk of Stroke Not Receive Oral Anticoagulants? Results of the Polish Atrial Fibrillation (POL-AF) Registry.

BACKGROUND: Most atrial fibrillation (AF) patients are at high risk of thromboembolic, and the use of oral anticoagulants (OACs) is advised in such cases. The aim of the study was to evaluate the frequency at which OACs were used in patients with AF and high risk thromboembolic complications, and identify factors that result in OACs not being used in the researched group of patients. METHODS: The prospective, multicenter and non-interventional POL-AF registry is a study that includes AF patients from ten Polish cardiology centers. They were consecutively hospitalized between January and December of 2019. All the patients in the study were of high stroke risk. RESULTS: A total of 3614 patients with AF and high stroke risk were included. Among the total study population, 91.5% received OAC therapy; antiplatelet therapy was prescribed for 3.7% of patients, heparin for 2.7%, and 2.1% of patients did not receive any stroke prevention therapy. Independent predictors of no OAC prescription were intracranial bleeding (OR 0.15, 95%CI 0.07-0.35, p < 0.001), gastrointestinal bleeding (OR 0.25, 95%CI 0.17-0.37, p < 0.001), cancer (OR 0.37, 95%CI 0.25-0.55, p < 0.001), hospitalization due to acute coronary syndrome (OR 0.48, 95%CI 0.33-0.69, p < 0.001), and anemia (OR 0.62, 95%CI 0.48-0.81, p < 0.001). CONCLUSIONS: Most AF patients with a high thromboembolic risk received OACs. The factors predisposing a lack of OAC use in these patients were conditions that significantly increased the risk of bleeding complications.

Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes.

The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

Are adipokines associated with atrial fibrillation in type 2 diabetes?

INTRODUCTION: The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. MATERIAL AND METHODS: The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. RESULTS: A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. CONCLUSION: In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

Randomized controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles (AFFECT EV) in acute myocardial infarction.

Activated platelets contribute to thrombosis and inflammation by the release of extracellular vesicles (EVs) exposing P-selectin, phosphatidylserine (PS) and fibrinogen. P2Y12 receptor antagonists are routinely administered to inhibit platelet activation in patients after acute myocardial infarction (AMI), being a combined antithrombotic and anti-inflammatory therapy. The more potent P2Y12 antagonist ticagrelor improves cardiovascular outcome in patients after AMI compared to the less potent clopidogrel, suggesting that greater inhibition of platelet aggregation is associated with better prognosis. The effect of ticagrelor and clopidogrel on the release of EVs from platelets and other P2Y12-exposing cells is unknown. This study compares the effects of ticagrelor and clopidogrel on (1) the concentrations of EVs from activated platelets (primary end point), (2) the concentrations of EVs exposing fibrinogen, exposing PS, from leukocytes and from endothelial cells (secondary end points) and (3) the procoagulant activity of plasma EVs (tertiary end points) in 60 consecutive AMI patients. After the percutaneous coronary intervention, patients will be randomized to antiplatelet therapy with ticagrelor (study group) or clopidogrel (control group). Blood will be collected from patients at randomization, 48 hours after randomization and 6 months following the index hospitalization. In addition, 30 age- and gender-matched healthy volunteers will be enrolled in the study to investigate the physiological concentrations and procoagulant activity of EVs using recently standardized protocols and EV-dedicated flow cytometry. Concentrations of EVs will be determined by flow cytometry. Procoagulant activity of EVs will be determined by fibrin generation test. The compliance and response to antiplatelet therapy will be assessed by impedance aggregometry. We expect that plasma from patients treated with ticagrelor (1) contains lower concentrations of EVs from activated platelets, exposing fibrinogen, exposing PS, from leukocytes and from endothelial cells and (2) has lower procoagulant activity, when compared to patients treated with clopidogrel. Antiplatelet therapy effect on EVs may identify a new mechanism of action of ticagrelor, as well as create a basis for future studies to investigate whether lower EV concentrations are associated with improved clinical outcomes in patients treated with P2Y12 antagonists.

Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus.

OBJECTIVES: The aim of this study was to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with platelet reactivity and antidiabetes treatment, as well as serum adipocytokine concentrations. METHODS: This observational, open-label study enrolled 149 patients. Serum BDNF, hematologic, biochemical parameters and platelet reactivity were measured. Blood samples were taken after the last acetylsalicylic acid dose. RESULTS: Patients with high BDNF levels were younger (65.60±8.956 vs. 68.59±8.516) and smoked cigarettes more frequently (14.6% vs. 4.1%); they were more commonly being treated by metformin (77.3% vs. 54%); had higher platelet counts (245.81±68.85 103/mm3 vs. 206.61±44.48 103/mm3); had shorter collagen-adenosine diphosphate closure time (CADP-CT) values (104.88±69.73 s vs. 140.93±86.63 s); had higher triglyceride concentrations (140.73±67.5 vs. 121.76±60.49) and had higher concentrations of serum thromboxane B2 (0.938±1.59 vs. 0.364±0.76). In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT >74 s. In multivariate backward stepwise analysis CADP-CT >141 s; adiponectin concentration >4.22 µg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median. CONCLUSIONS: Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment. Moreover, we showed an association between BDNF levels and platelet reactivity; we found that serum BDNF levels in patients with type 2 diabetes who had high platelet reactivity were higher than in subjects with normal platelet reactivity despite antiplatelet therapy.

Metabolic risk reduction in patients with schizophrenia treated with antipsychotics: recommendations of the Polish Psychiatric Association. / Redukcja ryzyka metabolicznego u chorych na schizofrenie przyjmujacych leki przeciwpsychotyczne ­ zalecenia Polskiego Towarzystwa Psychiatrycznego.

Patients with schizophrenia are susceptible to physical illnesses, which reduces their life expectancy by an average of 20 years compared with the general population. The most common physical illnesses amongst patients with schizophrenia are metabolic disorders and cardiovascular diseases. The aim of this paper is to present recommendations on metabolic risk reduction in patients with schizophrenia treated with antipsychotics, accepted as a position statement of the Polish Psychiatric Association for use in the management of persons suffering from schizophrenia in Poland. A routine assessment of metabolic risk is recommended for the early detection of metabolic disorders and to monitor the safety of the antipsychotic treatment. It includes: medical history, physical examination, laboratory tests. Each patient should undergo this assessment before the initiation of treatment, after 6 and 12 weeks of treatment, and at least once a year thereafter. In men and women suffering from schizophrenia who are over the age of 40 and 50 years, respectively, a cardiovascular risk assessment using the SCORE charts is also recommended. (1) Antipsychotics with a low potential to cause metabolic disorders should be preferred and administered at the appropriate dose in order to reduce metabolic risk. (2) If other agents found to cause metabolic disorders are used, the treatment should be modified by augmentation or by switching to another antipsychotic with a lower potential to cause metabolic disorders. (3) Consultation by an internal medicine specialist and medical treatment should be recommended. (4) Patients should be assisted in developing healthy eating habits, encouraged to pursue regular physical activity and (5) to quit smoking, drinking alcohol and using psychoactive substances.

Resistin is a prognostic factor for death in type 2 diabetes.

PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.

Heart failure patients with a previous coronary revascularization: results from the ESC-HF Registry.

BACKGROUND: Coronary revascularization is common in heart failure (HF). AIMS: Clinical characteristic and assessment of in-hospital and long-term outcomes in patients hospitalized for HF with or without a previous percutaneous coronary intervention (PCI) or a coronary artery bypass grafting (CABG). METHODS: The primary endpoint (PE) (all-cause death) and the secondary endpoint (SE) (all-cause death or hospitalization for HF-worsening) were assessed at one-year in 649 inpatients of the ESC-HF Pilot Survey. Additionally, occurrence of death during index hospitalization was evaluated. RESULTS: PCI/CABG-patients (32.7%) were more frequently male, smokers, had myocardial infarction, hypertension (HT), peripheral artery disease and diabetes. The non-PCI/CABG-patients more often had a cardiogenic shock and died in-hospital. The PE occurred in 33 of the 212 PCI/CABG-patients (15.6%) and in 56 of the 437 non-PCI/CABG-patients (12.8%; P=0.3). The SE occurred in 82 of the 170 PCI/CABG-patients (48.2%) and in 122 of the 346 non-PCI/CABG-patients (35.3%; P=0.01). Independent predictors of the PE in the PCI/CABG-patients were: lower left ventricular ejection fraction, use of antiplatelets; in the non-PCI/CABG-patients were: age, ACS at admission. Independent predictors of the SE in the PCI/CABG-patients were: diabetes, NYHA (New York Heart Association) class at admission, HT; in the non-PCI/CABG-patients were: NYHA class, haemoglobin at admission. Serum sodium concentration at admission was a predictor of the PE and the SE in both groups. Heart rate at discharge was a predictor of the PE and the SE in the non-PCI/CABG patients. CONCLUSIONS: The revascularized HF patients had a similar mortality and higher risk of death or hospitalizationsat 12 months compared with the non-PCI/CABG-patients. The revascularized patients had more comorbidities, while the non-PCI/CABG-patients had a higher incidence of cardiogenic shock and in-hospital mortality.

Heart failure in elderly patients: differences in clinical characteristics and predictors of 1-year outcome in the Polish ESC-HF Long-Term Registry.

INTRODUCTION    Heart failure (HF) is the leading cause of hospitalization in elderly patients. OBJECTIVES    The aim of the study was to examine the clinical profile and 1-year outcomes of elderly patients (aged ≥65 years) compared with younger patients (aged <65 years) hospitalized for HF decompensation, as well as clinical differences among elderly patients aged 65-74 years and those aged ≥75 years. PATIENTS AND METHODS    The primary endpoint (PE; all-cause death) and the secondary endpoint (SE; all-cause death or rehospitalization for HF worsening) were assessed at 1 year in a group of 765 hospitalized Polish participants of the ESC-HF Long-Term Registry. RESULTS    The PE was observed in 9.1% of patients aged <65 years; 18.5% of those aged ≥65 years (P = 0.0001); 14.5% of those aged 65-74 years; and 21.6% of those aged ≥75 years (P = 0.07). The SE occurred in 28.0% of patients aged <65 years; 36.1% of those aged ≥65 years (P = 0.04); 29.2% of those aged 65-74 years; and 41.2% of those aged ≥75 years (P = 0.01). Independent predictors of the PE in patients aged ≥65 years were as follows: chronic obstructive pulmonary disease (COPD), systolic blood pressure (SBP), New York Heart Association (NYHA) class, ß-blocker use; in patients aged 65-74 years: coronary revascularization, NYHA class, sodium, and creatinine; in patients aged ≥75 years: NYHA class and SBP. Independent predictors of the SE in patients aged ≥65 years were as follows: COPD, NYHA class, potassium, SBP, and physical activity; in patients aged <65 years: chronic kidney disease (CKD), NYHA, and SBP; in patients aged 65-74 years: NYHA and creatinine; and in patients aged ≥75 years, previous HF hospitalization, coronary artery disease, CKD, COPD, alcohol consumption, smoking, NYHA, and SBP. CONCLUSIONS    Elderly patients with HF differed from younger patients in terms of long-term outcome and prognostic factors. There were also important differences within the elderly group itself.

Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity but not to Genetic Polymorphisms within BDNF Encoding Gene in Patients with Type 2 Diabetes.

BACKGROUND: The aim of this study was to investigate the association between serum concentrations of the brain-derived neurotrophic factor (BDNF), platelet reactivity and inflammatory markers, as well as its association with BDNF encoding gene variants in type 2 diabetic patients (T2DM) during acetylsalicylic acid (ASA) therapy. MATERIAL/METHODS: This retrospective, open-label study enrolled 91 patients. Serum BDNF, genotype variants, hematological, biochemical, and inflammatory markers were measured. Blood samples were taken in the morning 2-3 h after the last ASA dose. The BDNF genotypes for selected variants were analyzed by use of the iPLEX Sequenom assay. RESULTS: In multivariate linear regression analysis, CADP-CT >74 sec (p<0.001) and sP-selectin concentration (p=0.03) were predictive of high serum BDNF. In multivariate logistic regression analysis, CADP-CT >74 sec (p=0.02) and IL-6 concentration (p=0.03) were risk factors for serum BDNF above the median. Non-significant differences were observed between intronic SNP rs925946, missense SNP rs6265, and intronic SNP rs4923463 allelic groups and BDNF concentrations in the investigated cohort. CONCLUSIONS: Chronic inflammatory condition and enhanced immune system are associated with the production of BDNF, which may be why the serum BDNF level in T2DM patients with high platelet reactivity was higher compared to subjects with normal platelet reactivity in this study.

Common carotid artery access for transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is an alternative method of treatment for severe symptomatic aortic stenosis in patients who are at high risk of surgical aortic valve replacement (AVR). In randomised clinical trials TAVI was shown to be superior to standard medical therapy in a cohort of inoperable patients and non-inferior to AVR in high-risk operable patients. Additionally, in a recent trial with self-expandable prosthesis use, TAVI was associated with lower mortality compared with surgery. Usually, femoral arteries are the most common vascular access to deliver the bioprosthesis; however, in some cases (up to 20%) this route may not be applied because of significant peripheral artery disease or tortuosity. In this article, we present the first two TAVI procedures in Poland performed via the left common carotid artery.

Association of adipokines and inflammatory markers with lipid control in type 2 diabetes.

INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.

Predictors of high platelet reactivity during aspirin treatment in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (DM2) is associated with high platelet reactivity both in patients who do not receive antiplatelet drugs and in those treated with acetylsalicylic acid (ASA). The pathomechanism of this phenomenon has not been fully understood. AIM: 1. To evaluate variability of platelet reactivity in patients with DM2 treated with oral antidiabetic drugs and receiving chronic ASA therapy. 2. To identify independent predictors of high platelet reactivity during ASA therapy in patients with DM2. METHODS: We studied 171 patients with DM2 treated with oral antidiabetic drugs and receiving long-term treatment with 75 mg of ASA daily, selected among the participants of the prospective AVOCADO study. Platelet function was simultaneously evaluated using 4 methods: 1. measurement of serum thromboxane B2 (TXB2) concentration; 2. measurement of urinary 11-dehydrothromboxane B2 (11-dhTXB2) concentration; 3. VerifyNow® automated analyser; 4. PFA-100® automated analyser.High platelet reactivity was defined as at least 3 of the following criteria: 1. serum TXB2 concentration in the upper quartile;2. urinary 11-dhTXB2 concentration in the upper quartile; 3. value ≥ 550 aspirin reaction units (ARU) by VerifyNow®;4. collagen-epinephrine closure time (CEPI-CT) below median of readings other than 300 s by PFA-100®. In all patients, DM2 control was evaluated, insulin resistance was measured using HOMA-IR, and routine laboratory tests were performed, including full blood count, renal function parameters, and inflammation markers. RESULTS: Mean patient age was 67.8 years, and median duration of DM2 was 5 years. We found poor agreement between different tests of platelet function. ARU ≥ 550 (VerifyNow®) was found in 14.0% of patients, and CEPI-CT below median of readings other than 300 s (PFA-100®) was found in 32.8% of patients. Our criteria of high platelet reactivity were met by 9.9% of patients. In multivariate logistic regression analysis, independent predictors of high platelet reactivity despite ASA therapy included chronic heart failure, current smoking, and higher leukocyte count. CONCLUSIONS: 1. Patients with DM2 are characterised by large variability of platelet reactivity, with little agreement between various methods. 2. Smoking, chronic heart failure, and subclinical inflammation may be associated with high platelet reactivity in patients with DM2 treated with ASA.

Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: the AVOCADO study.

BACKGROUND: The aim of the study was to compare the effects of 2 strategies of antiplatelet treatment (i.e., 150 mg ASA vs. 75 mg clpoidogrel) on plasma level of inflammatory markers in type 2 diabetes mellitus (T2DM) patients with high platelet reactivity (HPR). METHODS: Study cohort consisted of 304 T2DM patients on chronic ASA therapy (75 mg per day) participating in the Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Patients with HPR defined as Platelet Function Analyzer (PFA)-100 collagene/epinephrine closure time (CEPI-CT) < 193 s (n = 80) were randomized to 150 mg of ASA or 75 mg of clopidogrel in 2:3 ratio, respectively. Concentrations of the selected inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, solubleCD40 ligand (sCD40L), and high sensitivity C-reactive protein (hsCRP), were measured and compared in both treatment groups before and after 8 weeks of treatment in both groups. RESULTS: Out of 234 patients included into final analysis, the total of 34.2% (n = 80) patients displayed HPR, of which 14.1% (n = 33) were randomized into 150 mg of ASA group and 20.1% (n = 47) into 75 mg of clopidogrel group. Treatment with clopidogrel was a positive predictor (stepwise multiple regression analysis) of reduction of sCD40L concentration (odds ratio [OR] 4.15; p = 0.013), while treatment with 150 mg ASA was a positive predictor of reduction of IL-6 concentration (OR 4.38; p = 0.033). There was no statistically significant differences between clopidogrel and ASA 150 mg treatment in respect to predictive value for decreased hsCRP concentrations or increased TNF-α concentrations. CONCLUSIONS: Increasing the dose of ASA from 75 mg to 150 mg daily or switching ASA 75 mg to clopidogrel 75 mg daily may reduce concentrations of some inflammatory markers (in particular hsCRP, IL-6 and CD40L) in T2DM patients with HPR treated previously with 75 mg of ASA.

Do statins influence platelet reactivity on acetylsalicylic acid therapy in patients with type 2 diabetes?

BACKGROUND: Type 2 diabetes (T2DM) patients are at increased risk of cardiovascular events despite long-term acetylsalicylic acid (ASA) therapy. This study was performed to establish the prevalence of high platelet reactivity (HPR) on ASA in T2DM and to identify its predictors. METHODS: The study included 185 T2DM on chronic ASA therapy and to assess platelet reactivity during long-term ASA therapy, we applied the point-of-care method VerifyNow(®) aspirin test (Accumetrics, San Diego, CA, USA). RESULTS: Compared with the low platelet reactivity (LPR) group, patients with HPR had higher triglyceride levels (145 vs. 118 mg/dL, p = 0.041), were less frequently treated with statins (57.1% vs. 75.3%; p = 0.038) and tumor necrosis factor-alpha (TNF-α) concentrations were higher (2.15 vs. 1.74 pg/mL; p = 0.052). In a multivariate analysis only statin therapy (OR 0.375; 95% CI 0.15-0.91; P = 0.030) and lower concentrations of TNF-α (for each 1.0 pg/ml: or 1.3; 95% ci 1.00-1.72; p = 0.046) were predictive of LPR. CONCLUSIONS: Our study provides indirect evidence that the beneficial effect of statins on platelet activity may be related to their non-lipid-mediated, pleiotropic mechanisms of action. This might have been partly related to decreased platelet reactivity in patients receiving statin therapy. In our study in patients with T2DM, platelet reactivity on ASA therapy measured with VerifyNow(®) was associated with TNF-α concentrations and statin therapy. These results may imply a role for subclinical systemic inflammation and a beneficial effect of statins in the development of HPR in T2DM.