Guided de-escalation of DAPT in acute coronary syndrome patients undergoing percutaneous coronary intervention with BVS implantation: a post-hoc analysis from the randomized TROPICAL-ACS trial.

To investigate the safety and efficacy of an early platelet function testing (PFT)-guided de-escalation of dual antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVS). Early DAPT de-escalation is a new non-inferior alternative to 12-months DAPT in patients with biomarker positive ACS treated with stent implantation. In this post-hoc analysis of the TROPICAL-ACS trial, which randomized 2610 ACS patients to a PFT-guided DAPT de-escalation (switch from prasugrel to clopidogrel) or to control group (uniform prasugrel), we compared clinical outcomes of patients (n = 151) who received a BVS during the index PCI. The frequency of the primary endpoint (cardiovascular death, myocardial infarction, stroke or BARC ≥ 2 bleeding) was 8.8% (n = 6) in the de-escalation group vs. 12.0% (n = 10) in the control group (HR 0.72, 95% CI 0.26-1.98, p = 0.52) at 12 months. One early definite stent thrombosis (ST) occurred in the control group (day 19) and 1 possible ST (sudden cardiovascular death) in the de-escalation group (day 86), both despite prasugrel treatment and in a background of high on-treatment platelet reactivity assessed at day 14 after randomization (ADP-induced platelet aggregation values of 108 U and 59 U, respectively). A PFT-guided DAPT de-escalation strategy could potentially be a safe and effective strategy in ACS patients with BVS implantation but the level of platelet inhibition may be of particular importance. This hypothesis-generating post-hoc analysis requires verification in larger studies with upcoming BVS platforms.

Neopterin as a Biomarker in Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Upregulation of the immune system is regarded to play an important role in the etiopathobiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, neopterin (NP) has never been investigated in patients with PAH and CTEPH. OBJECTIVES: The aim of the study was to evaluate the concentration of NP in blood in order to examine its impact on outcome and relationship with disease severity in that population. METHODS: Serum concentration of NP was analysed prospectively in 50 patients (36 with PAH and 14 with CTEPH vs. 31 healthy controls) and assessed in relation to clinical parameters and outcome. RESULTS: NP concentration in the PAH and CTEPH groups combined was significantly higher than in the control group (8.68, 6.39-15.03 vs. 5.14, 4.16-5.98 nmol/L, p < 0.0000001). During 9 months of follow-up, clinical deterioration occurred in 18 patients (including 8 deaths), and NP concentration in this group was higher when compared to stable patients (15.6, 8.52-25.13 vs. 7.87, 6.18-9.89, p = 0.002). The cutoff value of NP derived from ROC curve analysis was 15.3 nmol/L (p = 0.002, AUC 0.77, p = 0.0004, HR = 4.35, 95% CI 1.43-13.18, log-rank test). On Cox regression analysis, NP predicted clinical deterioration (p = 0.009, 95% CI 1.01-1.06). NP correlated positively with NT-proBNP (p < 0.001), red blood cell distribution width (p < 0.001), and right atrium area (p = 0.002) and inversely with 6-min walking test (p = 0.002) and peak oxygen consumption (p = 0.001). CONCLUSIONS: NP concentration is increased in patients with PAH and inoperable CTEPH. Elevated NP concentration is associated with adverse clinical outcomes and correlates with clinical parameters.

Analysis of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease by HPLC-MS/MS method.

Fat-soluble vitamins play a pivotal role in the progression of atherosclerosis and the development of cardiovascular disease. Therefore, plasma monitoring of their concentrations may be useful in the diagnosis of these disorders as well as in the process of treatment. The study aimed to develop and validate an HPLC-MS/MS method for determination of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease. The analytes were separated on an HPLC Kinetex F5 column via gradient elution with water and methanol, both containing 0.1% (v/v) formic acid. Detection of the analytes was performed on a triple-quadrupole MS with multiple reaction monitoring via electrospray ionization. The analytes were isolated from plasma samples with liquid-liquid extraction using hexane. Linearity of the analyte calibration curves was confirmed in the ranges 0.02-2 µg/mL for retinol, 0.5-20 µg/mL for α-tocopherol, 5-100 ng/mL for 25-hydroxyvitamin D2 and 2-100 ng/mL for 25-hydroxyvitamin D3. Intra- and inter-assay precision and accuracy of the method were satisfactory. Short- and long-term stabilities of the analytes were determined. The HPLC-MS/MS method was applied for the determination of the above fat-soluble vitamin concentrations in patient plasma as potential markers of the cardiovascular disease progression.

Red Blood Cells Distribution Width as a Potential Prognostic Biomarker in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Red blood cells distribution width (RDW) predicts survival in cardiovascular diseases. Little is known about the variability of RDW level over time among patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). To our knowledge, RDW has never been analysed as a marker of response to specific treatment. MATERIALS AND METHODS: We retrospectively analysed 77 patients for: i) RDW measured during the last hospitalisation before death or during the last follow-up (RDWlast); ii) mean RDW from all hospitalisations during the entire follow-up of the patient (RDWmean); iii) maximum RDW of all hospitalisations of each patient (RDWmax). In order to assess response to specific treatment and association with prognosis, we compared RDW levels (obtained from 56 patients) before and 3 to 6 months after introduction or intensification of treatment in both the alive and deceased group. RESULTS: Twenty-eight of 77 patients died, whereas in specific drugs treatment response analysis, 22 of 56 patients died during follow-up. The cut-off values derived from the ROC analysis and assessed using the log-rank test were significant for RDWlast (p<0.0001), RDWmean (p<0.001) and RDWmax (p=0.02). A decrease in RDW levels after introduction or intensification of specific treatment was significant (p=0.015) in survivors, whereas there was no significance (p=0.29) in decrease in RDW levels in non-survivors after change of therapy. CONCLUSIONS: Red blood cells distribution width might be a potential prognostic biomarker in patients with PAH and inoperable CTEPH. The decrease in RDW level after introduction or escalation of PAH-targeted and CTEPH-targeted drugs is associated with a good treatment response and better prognosis.

Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite.

PURPOSE: A high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4). METHODS: The study included 63 patients undergoing elective coronarography or percutaneous coronary intervention. The population pharmacokinetic model was developed in the NONMEM 7.3 software, and first-order conditional estimation method with interaction was applied. Also, the influence of covariates was evaluated (age, weight, body mass index (BMI), obesity defined as BMI ≥ 30 kg/m2, sex, diabetes mellitus, co-administration of PPI or statins, presence of CYP2C19*2, CYP2C19*17, CYP3A4*1G alleles, and ABCB1 3435 TT genotype). RESULTS: It was found that the only significant covariate was the presence of CYP2C19*2 allele, which had an impact on lower conversion of clopidogrel to H4. As a result, predicted area under the time-concentration curve values was lower in carriers of this allele, with median 5.94 ng h/ml (interquartile range 3.92-12.51 [ng∙h/ml]) vs. 12.70 ng h/ml in non-carriers (interquartile range, 7.00-19.39 [ng∙h/ml]), respectively (p = 0.004). CONCLUSIONS: Developed model predicts that the only significant covariate influencing the observed concentrations and therefore the exposure to the active H4 metabolite is the presence of CYP2C19*2 allele.

Determinants of high on-treatment platelet reactivity and agreement between VerifyNow and Multiplate assays.

Dual antiplatelet therapy with clopidogrel is a regimen used before and after drug-eluting stent (DES) implantation. Point-of-care platelet reactivity assays are easy-to-use methods to determine adequate response to the drug. The aim of this study was a comparison of the two platelet reactivity assays: Multiplate® and VerifyNow® and an identification of factors potentially influencing the results of these tests, including common genetic polymorphisms. The study included 39 patients receiving 75 mg clopidogrel daily before angioplasty with DES implantation. Platelet reactivity was measured with Multiplate and P2Y12 VerifyNow assays. Genetic polymorphisms of CYP2C19*2, ABCB1 3435C > T, and CYP3A4*1G were determined with PCR-RFLP method and CYP2C19*17 was determined by means of an allele-specific PCR. Agreement between Multiplate and VerifyNow assays was poor (Cohen's κ = 0.056, p = .273). Hematocrit significantly negatively correlated with VerifyNow assayed platelet reactivity (r = -.487, p = .002). Female sex was significantly associated with higher VerifyNow assay results after adjustment to hematocrit (253.2 ± 47.6 PRU vs. 195.9 ± 56.9 PRU, p = .013) and the prevalence of high-on-treatment platelet reactivity (OR: 8.50; 95% CI 1.13-77.60, p = .024). Reactivity measured with Multiplate was lower in women (82.3 vs. 175.6 AU·min, p = .037) and in patients who received calcium channel blockers (74.7 vs. 191.7 AU·min, p = .002). None of the studied polymorphisms significantly influenced platelet aggregation measurements. In conclusion, different aspects modify between-patient variability of the Multiplate and VerifyNow assays and agreement between those two assays was poor.

Routine transfusion of platelet concentrates effectively reduces reoperation rate for bleeding and pericardial effusion after elective operations for ascending aortic aneurysm.

Patients with ascending aortic aneurysm undergoing complex surgical procedures are at increased risk of early postoperative excessive blood loss. The aim of this study was to analyze safety and efficacy of routine transfusions of platelet (PLT) concentrates in reduction of hemorrhagic postoperative complications. The study involved 396 consecutive patients (289 males and 107 females) with the mean age of 55.9 ± 13.6 years who underwent elective operations for aortic aneurysms. They were divided retrospectively into two groups, without (group A; n = 123) or with the routine use of PLTs (group B; n = 273). PLTs were transfused intraoperatively just after completion of cardiopulmonary bypass. Twelve patients in group A (9.8%) and 10 (3.7%) in group B required re-thoracotomy due to hemorrhage (p = 0.027). Routine transfusions of PLT concentrates reduced postoperative incidence of excessive pericardial effusion from 24.1% in group A to 2.1% in group B (p = 0.002). In a consequence, significantly less units (p < 0.0001) of red blood concentrates and fresh frozen plasma were transfused in group B than in group A. The rates of other adverse events in the early postoperative period did not differ between groups. Patients with pericardial effusion required 6.3 ± 2.7 additional days of hospitalization due to surgical re-intervention. Neither blood transfusion-related infections nor adverse reactions were noted. In conclusion, routine intraoperative transfusions of PLT concentrates in patients with ascending aortic aneurysms significantly reduced a need for re-intervention due to both early bleeding and late cardiac tamponade.

The Management of Supraventricular Tachyarrhythmias in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Atrial remodelling in pulmonary arterial hypertension (PAH) may lead to higher incidence of supraventricular arrhythmias (SVA). The purpose of this study was to evaluate the efficiency and safety of various methods for treatment of SVA in this group. METHODS: This was a single centre study. Forty-eight patients (33 women and 15 men) aged 19-77 years (median 49 years) were enrolled. There were 30 patients with idiopathic PAH, 10 had PAH associated with connective tissue disease, and eight with congenital heart disease. A retrospective analysis was performed to estimate the prevalence and type of supraventricular arrhythmias, as well as efficiency and safety of treatment methods. Mean follow-up period was 28.8±17.7 months. RESULTS: Supraventricular arrhythmias occurred in 17 patients (35%) and appeared to be atrial fibrillation, flutter or tachycardia. Supraventricular arrhythmias coexisted with elevated mean right atrial pressure in 75%. Four patients had more than one type of SVA. A flutter-like macro-reentrant form of atrial tachycardia dependent on cavo-tricuspid isthmus was found in four cases. The treatment of SVA included typical methods: antiarrhythmic drugs, direct current cardioversion (DCC), and radiofrequency (RF) ablation. All of the therapeutic methods were effective in managing acute arrhythmia. Three patients required re-ablation. Overall mortality: 14 patients (29%) in the whole study group, including six in SVA group (35%) and eight without SVA (26%). CONCLUSIONS: In patients with PAH DCC, pharmacological cardioversion and RF ablation can be applied safely and effectively. Flutter-like macro-reentrant atrial tachycardia dependent on cavo-tricuspid isthmus is observed in this group. It is more challenging, but possible, to successfully treat this arrhythmia with RF ablation.

Selected Psychosocial Factors, Nutritional Behavior, and the Analysis of Concentrations of Selected Vitamins in Patients with Cardiovascular Diseases.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions, overweight/obesity, hypertension, an abnormal lipid profile, vitamin deficiencies, diabetes, and psychological factors. This study aimed to assess the relationships between psychosocial and nutritional factors in a group of 61 patients with CVD (i.e., atherosclerosis, hypertension, ischemic heart disease, and myocardial infarction) and their possible impact on the course of the disease. The plasma concentrations of vitamins A, E, D, and ß-carotene were determined using validated HPLC-MS/MS, while the lipid profile was analyzed enzymatically. Psychosocial factors and nutritional behaviors were assessed using author-designed questionnaires. Over 50% of patients had 25-OH-D3 and retinol deficiencies, while >85% of patients exhibited significant deficiencies in α-tocopherol and ß-carotene. The lipid profile showed no specific relationship with any particular CVD. Dietary behavior minimally impacted biochemical parameters except for higher ß-carotene concentrations in the group with higher fruit and vegetable intake. The negative impact of the CVD on selected parameters of quality of life was noticed. To increase the effectiveness of the prevention and treatment of CVD, the need for interdisciplinary cooperation observed between doctors, psychologists, and specialists in human nutrition seems to be justified.

Predictive value of systemic inflammatory response index (SIRI) for complex coronary artery disease occurrence in patients presenting with angina equivalent symptoms.

BACKGROUND: Currently, atherosclerotic cardiovascular disease is the major cause of mortality world-wide. Inflammatory processes are postulated to be a major driving force for coronary plaque initiation and progression and can be evaluated by simple inflammatory markers from whole blood count analysis. Among hematological indexes, systemic inflammatory response index (SIRI) is defined as a quotient of neutrophils and monocytes, divided by lymphocyte count. The aim of the present retrospective analysis was to present the predictive role of SIRI for coronary artery disease (CAD) occurrence. METHODS: There were 256 patients (174 [68%] men and 82 [32%] women) in the median (Q1-Q3) age of 67 (58-72) years enrolled into retrospective analysis due to angina pectoris equivalent symptoms. A model for predicting CAD was created based on demographic data and blood cell parameters reflecting an inflammatory response. RESULTS: In patients with single/complex coronary disease the logistic regression multivariable analysis revealed predictive value of male gender (odds ratio [OR]: 3.98, 95% confidence interval [CI]: 1.38-11.42, p = 0.010), age (OR: 5.57, 95% CI: 0.83-0.98, p = 0.001), body mass index (OR: 0.89, 95% CI: 0.81-0.98, p = 0.012), and smoking (OR: 3.66, 95% CI: 1.71-18.22, p = 0.004). Among laboratory parameters, SIRI (OR: 5.52, 95% CI: 1.89-16.15, p = 0.029) and red blood cell distribution width (OR: 3.66, 95% CI: 1.67-8.04, p = 0.001) were found significant. CONCLUSIONS: Systemic inflammatory response index, a simple hematological index, may be helpful in patients with angina equivalent symptoms to diagnose CAD. Patients presenting with SIRI above 1.22 (area under the curve: 0.725, p < 0.001) have a higher probability of single and complex coronary disease.

Coronary Artery Disease and Inflammatory Activation Interfere with Peripheral Tissue Electrical Impedance Spectroscopy Characteristics-Initial Report.

BACKGROUND: The electrical properties of cells and tissues in relation to energy exposure have been investigated, presenting their resistance and capacitance characteristics. The dielectric response to radiofrequency fields exhibits polarization heterogeneity under pathological conditions. The aim of the study was to analyze the differences in changes in resistance and capacitance measurements in the range from 1 kHz to 1 MHz, combined with an assessment of the correlation between the results of electrical impedance spectroscopy (EIS) and inflammatory activation. METHODS: In the prospective study, EIS was performed on the non-dominant arm in 29 male patients (median (Q1-Q3) age of 69 (65-72)) with complex coronary artery disease and 10 male patients (median (Q1-Q3) age of 66 (62-69)) of the control group. Blood samples were collected for inflammatory index analysis. RESULTS: The logistic regression analysis revealed a negative correlation with inflammatory indexes, including neutrophil to lymphocyte ratio (NLR) in the CAD group in the frequency of 30 kHz (p = 0.038, r = -0.317) regarding EIS resistance measurements and a positive correlation in CAD group in the frequency of 10 kHz (p = 0.029, r = -0.354) regarding EIS capacitance. CONCLUSIONS: The bioelectric characteristics of peripheral tissues measured by resistance and capacitance in EIS differ in patients with coronary artery disease and in the control group. Electrical impedance spectroscopy reveals a statistically significant correlation with inflammatory markers in patients with CAD.

Predictive role of monocyte count for significant coronary artery disease identification in patients with stable coronary artery disease.

BACKGROUND: The coronary artery disease (CAD) remains the leading cause of morbidity that is characterized by broad spectrum of symptoms. Up to 30% of performed angiographies reveal normal coronary arteries. The aim of the study was to find simple predictor for significant epicardial artery stenosis among patients with chronic coronary syndrome. METHODS: There were 187 patients (131 (709%) men and 56 (30%) women) in the median (Q1-Q3) age of 67 [58-72] presenting with stable CAD symptoms enrolled into the present retrospective analysis. The demographical, clinical and laboratory characteristics between patients with normal and significant coronary artery stenosis were compared. RESULTS: The multivariable analysis revealed coexistence of hypercholesterolemia as significant differentiation factor (odds ratio [OR]: 4.38, 95% confidence interval [CI]: 1.78-10.80, p = 0.001) for significant CAD and inverse relation to serum high density lipoprotein (OR: 0.19, 95% CI: 0.05-0.72, p = 0.015) and relation to creatinine concentration (OR: 1.03, 95% CI: 1.00-1.05, p = 0.012). Among whole peripheral blood count analysis, the significant relation was noticed to be hemoglobin concentration (OR: 1.09, 95% CI: 1.10-1.18, p = 0.022) and monocyte count (OR: 32.3, 95% CI: 1.09-653.6, p = 0.017). Receiver operator curve revealed (AUC: 0.641, p = 0.001) with the optimal cut-off value above 0.45 K/uL for monocyte, yelding sensitivity of 81.82% and specificity of 58.06%. CONCLUSIONS: The peripheral monocyte count above 0.45 k/uL may be considered as a predictor of significant coronary artery disease in symptomatic patients with chronic coronary syndrome.

Dual antiplatelet therapy for reduction in mortality in patients with acute and chronic coronary syndromes.

Dual antiplatelet therapy (DAPT) is a foundation of successful coronary artery disease management. DAPT is recommended according to ESC guidelines for 6 months following elective percutaneous coronary intervention and for 12 months following the acute coronary syndrome (ACS). ACS are the most cost-consuming type of the ischemic heart disease, which prominently requires hospital treatment. This risk significantly increases shortly after stopping DAPT, which is typical in most patients after 12 months following acute myocardial infarction (AMI). Therefore, one of the goals of long-term treatment of such patients should be the identification of those at increased risk of subsequent events, for whom prolonged DAPT will bring clinical benefits. It has been documented that prasugrel and ticagrelor, compared to clopidogrel, significantly reduce the incidence of major adverse cardiovascular events (MACE) in ACS patients. In addition to lowering composite ischemic endpoint, ticagrelor significantly reduced all-cause and cardiovascular mortality. The long-term use of ticagrelor in patients with a previous myocardial infarction was also related to a significant reduction in MACE. In patients who had a myocardial infarction 1-3 years earlier, the addition of ticagrelor to aspirin resulted in a substantial reduction in the composite endpoint of cardiovascular death, myocardial infarction, or stroke at the expense of a small but significant increase in bleedings. Hypothetical calculations have shown that replacing clopidogrel with ticagrelor in all patients with AMI in Poland would save more than three thousand lives within 12 months after AMI and more than a thousand within the following 2 years.

Optimal duration and combination of antiplatelet therapies following percutaneous coronary intervention: a meta-analysis.

INTRODUCTION: The ideal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still unknown. In this meta-analysis, we aimed to compare very short-term (1-3 months), short-term (6 months), standard-term (12 months) and long-term (>12 months) DAPT durations for efficacy and safety. METHODS: Overall DAPT comparisons were classified as "any shorter-term"/"any longer-term" DAPT. The primary outcome was a composite of major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke and cardiovascular death). The primary safety outcome was major bleeding. RESULTS: Twenty-six studies comprising 103.394 patients were included. Compared with standard-term DAPT duration, very short-term DAPT duration with subsequent drop of aspirin (RR 1.06, 95% CI, 0.95-1.18, p = 0.26) or drop of the P2Y12 inhibitor (RR 0.92, 95% CI, 0.72-1.16, p = 0.47) was not associated with a higher risk of MACE. Any longer-term compared with any shorter-term DAPT durations led to a significantly lower risk of MACE (RR 0.88, 95% CI, 0.81-0.96, p = 0.002), but a significantly higher risk of BARC 3-5 major bleeding events (RR 1.63, 95% CI, 1.22-2.17, p = 0.001). In the ACS subgroup receiving prasugrel or ticagrelor but not clopidogrel, any longer-term DAPT duration was associated with a significantly lower risk of MACE compared to any shorter-term DAPT duration (RR 0.84, 95% CI, 0.77-0.92, p = 0.0001). CONCLUSION: DAPT may be shortened to 1-3 months in patients with low ischemic but high bleeding risk followed by aspirin or P2Y12 monotherapy. Prasugrel or ticagrelor based DAPT may be extended to >12 months in case of high ischemic and low bleeding risk. PROSPERO REGISTRATION NO: CRD42020163719.

Mean platelet volume-to-platelet count ratio after elective cardiac surgical procedures is superior in reflecting platelets metabolic hyperactivity compared to other routine morphological platelet indices: A preliminary report.

BACKGROUND: Excessive metabolic excitation of platelets after cardiac procedures may be related to some adverse events but assessment of their metabolic activity is not routine. The purpose of this study was to evaluate which of the basic platelet morphological parameters best reflects their metabolic status. METHODS: The blood samples of 22cardiac surgical patients (mean age of 62.3 ± 10.3 years) were taken before surgery (BS), and 1, 24 and 48 hours after the operation. Correlations between morphological platelet parameters (platelet count [PLT], mean platelet volume [MPV], platelet distribution width [PDW] and MPV/PLT) and their metabolic activity (total concentration of malondialdehyde [MDA] and MDA/PLT) were estimated. RESULTS: Significant decline in PLT after operation (from 223 ± 44 × 10¹²/L to 166 ± 57 × 10¹²/L) was accompanied by marked increase in MPV (from 8.4 ± 0.9 fL to 9.1 ± 1.2 fL) and no change of PDW. Consequently, MPV/PLT index increased significantly after procedures from (median with IQR) 0.038 (0.030-0.043) to 0.053 (0.043-0.078). Simultaneously, a significant increase in total platelet MDA content and MDA/PLT was noted reaching peak levels soon after operation. The strongest correlation was observed between MPV/PLT and MDA/PLT (r = 0.56; p < 0.001), although the others were also found to be significant (MDA/PLT vs. MPV; r = 0.35; MDA/PLT vs. PDW; r = 0.34). CONCLUSIONS: Among basic morphological parameters and indices, the MPV-to-PLT ratio reflects the best metabolic status of platelets in cardiac surgical patients.

Platelet function in patients undergoing surgical and transcatheter aortic valve replacement: a comparative study.

BACKGROUND: Intervention-induced platelet hypercoagulability may pose a risk of serious adverse events for patients. AIMS: This study aimed to assess whether surgical and transcatheter aortic valve replacement (SAVR and TAVR) differ in periprocedural platelet activity. METHODS: The total number of 24 patients with a mean age (SD) of 71 (13) years who underwent SAVR (n = 12) or TAVR (n = 12) were recruited for the study. The following parameters were evaluated at 4 time-points: (i) platelet indices: total platelet count (PLT), platelet distribution width (PDW) and mean platelet volume (MPV), (ii) MPV/PLT ratio, (iii) platelet level of lipid peroxidation: malondialdehyde (MDA) content and MDA/PLT ratio. Eventually, percentage variations of PLT, PDW, and MPV in relation to the baseline values were determined. RESULTS: MPV/PLT ratio increased significantly after procedures in both groups (P = 0.01 in TAVI and P = 0.01 in SAVR). MDA concentrations were significantly higher when assessed directly post-procedure (P = 0.04) as well as 24 hours later (P = 0.01) in the SAVR and TAVI groups. The indirect parameter of platelet activity indexed for platelet counts (MDA/PLT) was comparable between both groups before and 48 hours after procedures, but was significantly higher in SAVR patients, particularly after 24 hours after interventions (P = 0.04; medians TAVR vs SAVR, respectively). CONCLUSIONS: Standard surgical aortic valve replacement is associated with a more pronounced platelet reaction to intervention-induced injury, as compared to the transcatheter-based procedure. The importance of these laboratory findings requires further investigation focused on early and late clinical outcomes.

Prognostic Value of Oxidative Stress Markers in Patients with Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertension.

Oxidative stress is regarded to play a crucial role in the pathophysiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This study evaluated the prognostic value of serum oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), catalase activity (CAT), and superoxide activity (SOD)) in patients with PAH and CTEPH (n = 45). During 13 months of follow-up (median 9 months), clinical deterioration occurred in 14 patients (including 2 deaths). On the Cox regression analysis, MDA, TAC, and CAT were associated with clinical deterioration (p = 0.0068, HR = 1.42, 95% CI: 1.10-1.82; p = 0.0038, HR = 0.033, 95% CI: 0.0032-0.33; and p = 0.046, HR = 0.20, 95% CI: 0.04-0.98, respectively). There was no significant difference in SOD (p = 0.53, HR = 0.97, 95% CI: 0.87-1.08). The cut-off value derived from ROC curve analysis was 3.79 µM (p = 0.0048, AUC = 0.76, 95% CI: 0.62-0.91) for MDA, 0.49 mM (p = 0.027, AUC = 0.71, 95% CI: 0.18-0.47) for TAC, and 1.34 U/L (p = 0.029, AUC = 0.71, 95% CI: 0.55-0.86) for CAT. MDA in the group with deterioration was higher (p = 0.0041), while TAC as well as CAT were lower (p = 0.027 and p = 0.028, respectively) when compared to stable patients. Survival without clinical deterioration was significantly longer in patients with lower MDA (p = 0.037, HR = 0.37, 95% CI: 0.12-1.14, log-rank), higher TAC (p = 0.0018, HR = 0.19, 95% CI: 0.06-0.60, log-rank), and higher CAT (p = 0.044, HR = 0.31 95% CI: 0.11-0.88, log-rank). Markers of oxidative stress such as MDA, TAC, and CAT were associated with adverse clinical outcomes in patients with PAH and inoperable or residual CTEPH.

The Effect of Mushroom Extracts on Human Platelet and Blood Coagulation: In vitro Screening of Eight Edible Species.

Cardiovascular diseases remain the leading global cause of mortality indicating the need to identify all possible factors reducing primary and secondary risk. This study screened the in vitro antiplatelet and anticoagulant activities of hot water extracts of eight edible mushroom species (Agaricus bisporus, Auricularia auricularia-judae, Coprinus comatus, Ganoderma lucidum, Hericium erinaceus, Lentinula edodes, Pleurotus eryngii, and Pleurotus ostreatus) increasingly cultivated for human consumption, and compared them to those evoked by acetylsalicylic acid (ASA). The antioxidant capacity and concentration of polysaccharides, phenolic compounds, organic acids, ergosterol, macro elements, and trace elements were also characterized. The most promising antiplatelet effect was exhibited by A. auricularia-judae and P. eryngii extracts as demonstrated by the highest rate of inhibition of adenosine-5'-diphosphate (ADP)-induced and arachidonic acid (AA)-induced aggregation. The response to both extracts exceeded the one evoked by 140 µmol/L of ASA in the ADP test and was comparable to it in the case of the AA test. Such a dual effect was also observed for G. lucidum extract, even though it was proven to be cytotoxic in platelets and leukocytes. The extract of P. ostreatus revealed an additive effect on AA-induced platelet aggregation. None of the mushroom extracts altered the monitored coagulation parameters (prothrombin time, prothrombin ratio, and International Normalized Ratio). The effect of mushroom extracts on platelet function was positively related to their antioxidative properties and concentration of polysaccharides and ergosterol, and inversely related to zinc concentration. The study suggests that selected mushrooms may exert favorable antiplatelet effects, highlighting the need for further experimental and clinical research in this regard.

Transcatheter Aortic Valve Replacement Is Associated with Less Oxidative Stress and Faster Recovery of Antioxidant Capacity than Surgical Aortic Valve Replacement.

The objective of this study was to compare oxidative stress indices in 24 patients (mean ± SD age 71 ± 13 years) undergoing surgical aortic valve replacement (SAVR) versus transcatheter aortic valve replacement (TAVR). Serum total antioxidant capacity (TAC), copper/zinc ratio (Cu/Zn), activity of lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS) were assessed at four different time-points: pre-procedure, immediately post-procedure, and one day and two days after the procedure. All oxidative stress parameters were comparable in both groups pre-procedure. TAC decreased significantly when assessed immediately after procedures in both groups (p < 0.001); however, the magnitude of the reduction was more pronounced after SAVR (88% decrease from baseline: 1.8 ± 0.1 vs. 0.2 ± 0.03 mM) compared to TAVR procedures (53% decrease from baseline: 1.9 ± 0.1 vs. 1.0 ± 0.1 mM; p < 0.001). TAC returned to baseline two days after TAVR in all patients, but was still reduced by 55% two days after SAVR. In concordance, TBARS levels and Cu/Zn ratio increased significantly with maximum levels immediately after procedures in both groups (p < 0.001), but the magnitude of the increase was significantly higher in SAVR compared to TAVR (TBARS: 3.93 ± 0.61 µM vs. 1.25 ± 0.30 µM, p = 0.015; Cu/Zn ratio: 2.33 ± 0.11 vs. 1.80 ± 0.12; p < 0.001). Two days after the procedure, TBARS levels and the Cu/Zn ratio returned to baseline after TAVR, with no full recovery after SAVR. TAVR is associated with a lesser redox imbalance and faster recovery of antioxidant capacity compared to SAVR.

Optimal Timing of P2Y12 Inhibitor Loading in Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND AND AIM: The timing of P2Y12 inhibitor loading in patients undergoing percutaneous coronary intervention (PCI) is a matter of debate. The aim of our study was to compare the efficacy and safety of oral P2Y12 inhibitors: clopidogrel, ticagrelor and prasugrel administered at two different time points in relation to PCI: early (> 2 hours pre-PCI) versus late (< 2 hours pre-PCI or post-PCI). METHODS: This is a systematic review and meta-analysis. Randomized controlled trials and non-randomized studies were included. Outcomes evaluated were combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), target vessel revascularization, death and bleeding complications. Summary estimates of the relative risks with therapy were calculated. RESULTS: Twenty-three studies met the selection criteria and included 60,907 patients. Early P2Y12 inhibitor loading was associated with a 22% relative risk reduction (RRR) of MACE (95% confidence interval [CI] = 0.68-0.89; p < 0.001). Early clopidogrel loading was associated with a 25% RRR of MACE (95% CI = 0.65-0.85; p < 0.001), a 30% RRR of MI (95% CI = 0.6-0.82; p < 0.0001) and 25% RRR of death (95% CI = 0.64-0.87; p = 0.0002), without an impact on major bleedings. In ST-elevation myocardial infarction as well as non-ST elevation acute coronary syndrome (NSTE-ACS), early clopidogrel loading resulted in 35 and 22% RRR in 30 days MACE (p < 0.001), respectively, with no impact in elective PCI. Whereas early loading with prasugrel and ticagrelor did not improve ischaemic outcomes, prasugrel administered early increased bleeding risks in NSTE-ACS. CONCLUSION: Early clopidogrel loading is associated with a better efficacy and similar safety, whereas timing of ticagrelor or prasugrel loading had no effects on ischaemic events.