Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

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.

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.

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.

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.

The incidence of aspirin resistance in heart transplantation recipients.

INTRODUCTION: Coronary allograft vasculopathy can cause as many deaths as infections or rejection episodes within 3 years following heart transplantation. AIM: To compare the aspirin resistance rate in an allograft heart transplantation population and in a control group by laboratory tests including the Aspirin-Resistant Patients Identification Test (ASPItest). MATERIAL AND METHODS: A total of 24 heart recipients (20 men and 4 women) at a mean age of 48 ±13 years who underwent routine clinical follow-up were consecutively enrolled in group 1. The control group consisted of 24 patients (19 men and 5 women) at a mean age of 64 ±7 years waiting for coronary artery bypass grafting in our department. All patients were treated with a standard dose of 75 mg aspirin (ASA) daily. RESULTS: Aspirin resistance was evaluated by the Multiplate platelet function test. The ASPItest revealed a mean value of 27 ±22 U in the transplant group. Results above 30 U were obtained in 8 (34%) patients, with a mean value of 50.3 ±20.6 U, indicating aspirin resistance. In the control group ASPItest results above 30 U were obtained in 5 (20%) patients, with a mean value of 43.3 ±6.4 U. CONCLUSIONS: There is a high incidence (34% vs. 20%, NS) of ASA resistance in heart transplantation recipients and in the general population, respectively.

Platelets redox balance assessment: Current evidence and methodological considerations.

Altered function of platelets can lead to cardiovascular complications in numerous disorders. Various studies aimed to investigate mechanisms triggering platelets activation cascade show a significant role of reactive oxygen species (ROS) in this matter. Moreover, ROS are known causal factor of oxidative stress that can result in DNA, lipid and protein damage. This review aims to comprehensively present the variety of methods that are potentially useful in assessment of platelets redox balance, such as intracellular concentration of particular ROS, activity of antioxidant enzymes, reduced/oxidized glutathione ratio, level of lipid peroxidation, Cu/Zn ratio, and molecular oxygen consumption. They may help to establish the platelet-related etiological factors in different disorders and to evaluate the antiplatelet therapies. The advantages and limitations of these methods are also discussed. The present paper highlights that clinicians may benefit from implementation of such tools and further encourages developing interdisciplinary evidence-based practice.

Short- and mid-term outcome of transcatheter aortic valve implantation in patients with advanced age.

BACKGROUND: In patients treated with transcatheter aortic valve implantation (TAVI), age is recognized as one of the most important risk factors. The aim of our study was to evaluate whether early and mid-term results of TAVI were worse in patients over 85 year old compared with the younger population. METHODS: From September 2010 to November 2015, 162 consecutive patients (mean age 78.4 ± 7.1 years, 47.5% females) underwent TAVI in our Institution. Patients were divided into two groups: 1) elderly (≥ 85 year old) and 2) younger patients (< 85 year old). Primary clinical study endpoints were the fol-lowing: death, myocardial infarction, stroke, major and minor access site, and bleeding complications. The secondary endpoints included: pacemaker implantation rate, paravalvular leakage, acute kidney injury, and duration of hospitalization. RESULTS: Twenty-six patients were 85 or older (mean 87.5 ± 2.1). In the remaining 136 (84%), the average age was 76.7 ± 6.4. Baseline clinical profiles were similar in both groups, though history of pre-vious cardiac surgery (p = 0.0047) and chronic obstructive pulmonary disease (p = 0.0099) were more common in the younger group, and glomerular filtration rate was lower in the older group (p = 0.045). Major, life threatening and minor bleeding complications, as well as vascular access site complications did not differ between the two groups. Rates of myocardial infarction and stroke were comparably low in both groups. Similar results were also found in the incidence of secondary endpoints. In-hospital mortality and 1-year mortality did not differ between groups. CONCLUSIONS: TAVI in patients aged 85 and older is still a relatively safe procedure and age itself should not be a discriminatory factor in TAVI qualification. (Cardiol J 2017; 24, 4: 358-363).

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.

Significance of antiplatelet therapy in emergency myocardial infarction treatment.

Antiplatelet drugs play a crucial role in the treatment of patients with myocardial infarction, particularly in association with percutaneous coronary intervention. Their main advantage is the reduction of adverse ischemic incidents and the major disadvantage is the increase in the frequency of hemorrhages. Thus, the choice of appropriate drug depends on the right risk assessment of the development of these complications in individual patients. The aim of this article is to provide an update of antiplatelet therapy in emergency myocardial infarction treatment. Currently, the most important role in the process of platelet inhibition is played by ADP P2Y12 blockers: clopidogrel, prasugrel and ticagrelor. Clopidogrel and prasugrel belong to thienopyridines, and ticagrelor, a drug of irreversible action, is an analogue of adenosine triphosphate. By 2011 clopidogrel, alongside aspirin, had the highest recommendations of world cardiology associations for acute coronary syndrome treatment. The position on clopidogrel was changed following the publication of European Society of Cardiology guidelines for STEMI in 2012 which advocate the administration of acetylsalicylic acid (ASA) and ADP receptor blocker (in combination with ASA). It needs to be stressed that prasugrel and ticagrelor received class IB recommendation, while clopidogrel received only IC. However, the most recent studies aimed at introducing a new generation of antiplatelet drugs of high efficacy in prevention of ischemic incidents and of reversible action: cangrelor and elinogrel, which raise hopes for better prognosis for myocardial infarction patients.

Clinical pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases.

BACKGROUND AND OBJECTIVE: Approximately 5-40 % of patients treated with clopidogrel do not display an adequate antiplatelet response. Clopidogrel resistance may be caused by insufficient drug absorption or impaired metabolic activation of the drug. The aim of this study was to evaluate the pharmacokinetics of clopidogrel and its metabolites in plasma samples from patients treated with high and low doses of clopidogrel, to obtain a possible explanation for antiplatelet resistance. METHODS: The study included patients receiving either a single 300 mg loading dose of clopidogrel (n = 17) or a 75 mg dose (n = 45) for at least 7 days before sample collection. The concentrations of clopidogrel and its metabolites-the inactive H3 and the pharmacologically active H4 isomers of the thiol metabolite and the inactive carboxylic acid metabolite-in plasma samples (stabilized with 2-bromo-3'-methoxyacetophenone) from three patients after 300 mg and from 41 patients after 75 mg of the drug were determined using a validated high-performance liquid chromatography method with tandem mass spectrometry. The non-stabilized samples from the remaining patients were analysed using a validated capillary electrophoresis method. The calculated concentrations were used to determine the pharmacokinetic parameters of the analytes. The pharmacodynamic response to clopidogrel treatment, expressed as adenosine diphosphate-induced platelet aggregation, was measured using a Multiplate analyser. RESULTS: The pharmacokinetic parameter values for the H3 and H4 isomers determined in the studied group of patients treated with clopidogrel 75 mg (maximum plasma concentration [C max] 5.29 ± 5.54 and 7.13 ± 6.32 ng/mL for H3 and H4, respectively; area under the plasma concentration-time curve from time zero to time t [AUC t ] 7.37 ± 6.71 and 11.30 ± 9.58 ng·h/mL for H3 and H4, respectively) were lower than those reported in healthy volunteers, according to the literature data. Platelet aggregation measured with a Multiplate analyser ranged between 37 and 747 AU·min. A significant correlation was found between the C max of the active H4 isomer and platelet aggregation (p = 0.025). CONCLUSION: The C max of the active H4 isomer and platelet aggregation measured by the Multiplate analyser may serve as markers of the patient response to clopidogrel therapy.