ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ТРОМБОЦИТАРНОГО ФАКТОРА РОСТА PDGF-BB И ST2 ПРИ ОТТОРЖЕНИИ ТРАНСПЛАНТИРОВАННОГО СЕРДЦА

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods. The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results. No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2.Цель: определить связь концентрации биомаркеров sCD40L, PDGF-BB, PlGF-1, ST2 в плазме крови реципиентов сердца с наличием и выраженностью гистохимических и иммуногистохимических признаков отторжения сердечного трансплантата.Материалы и методы. В исследование включены 98 пациентов с трансплантированным сердцем в возрасте от 12 до 69 (43 ± 14) лет, из них 78 мужчин. У 68 реципиентов до трансплантации сердца была диагностирована дилатационная кардиомиопатия, у 30 – ишемическая болезнь сердца. Концентрацию плацентарного фактора роста (PlGF-1), фактора роста тромбоцитов (PDGF-BB), растворимой формы лиганда CD40 (sCD40L) измеряли с использованием мультиплексной технологии; концентрацию стимулирующего фактора роста ST2 – с помощью иммуноферментного анализа.Результаты. Концентрация каждого биомаркера не зависела от пола, возраста и диагноза до трансплантации. У 37 пациентов (по результатам 49 биопсий) были диагностированы признаки отторжения. Гистохимические признаки острого клеточного отторжения – у 30 реципиентов (в 41 биоптате): 1А – у 25 пациентов (в 34 биоптатах), 1В – у двух пациентов (в трех биоптатах), 3А – у четырех пациентов. Иммуногистохимические признаки антителоопосредованного отторжения выявлены у трех пациентов. Сочетание острого клеточного и гуморального отторжения обнаружено у четырех пациентов (в пяти биоптатах). Концентрация PDGF-BB, измеренная в день эндомиокардиальной биопсии, была достоверно выше у пациентов с отторжением (p = 0,02). У реципиентов сердца с уровнем PDGF-BB выше медианы (2473,7 пг/мл) риск отторжения был в 1,64 раза выше, чем у пациентов с уровнем ниже медианы. У реципиентов с концентрацией и ST2, и PDGF-BB, превышающей значения медианы, относительный риск отторжения возрастал до 2,11 ± 0,34 [95% ДИ 1,08–4,11]. Наибольшей диагностической значимостью в отношении отторжения трансплантата обладала панель из трех биомаркеров (sCD40L, PlGF-1, ST2): RR = 2,51 ± 0,38 [95% ДИ 1,18–5,3].Заключение. PDGF-BB обладает умеренной прогностической значимостью в отношении отторжения трансплантированного сердца. Наибольшей диагностической значимостью обладает панель из трех биомаркеров: sCD40L, PlGF-1, ST2

THE DIAGNOSTIC VALUE OF PLATELET-DERIVED FACTOR PDGF-BB AND ST2 IN HEART REJECTION

Aim: to determine the association between plasma concentrations of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) with histochemical and immunohistochemical signs of heart rejection.Materials and methods. The study included 98 heart recipients aged from 12 to 69 (mean age 43 ± 14) years, of which 78 men. In 68 patients dilated cardiomyopathy was diagnosed, 30 recipients were diagnosed with coronary heart disease. The concentrations of placental growth factor (PlGF-1), platelet-derived growth factor (PDGF-BB), soluble CD40 ligand (sCD40L) were measured using xMAP technology. The concentrations of ST2 cardiac biomarker were measured by ELISA.Results. No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, PlGF-1, ST2) and gender, age and diagnosis. The rejection was diagnosed via biopsy in 49 biopsies taken from 37 recipients. 1A rejection was found in 25 patients (34 biopsies), 1B rejection was identifi ed in 2 patients (3 biopsies), 3A rejection was diagnosed in 4 patients. Immunohistochemical signs of humoral rejection were identifi ed in 3 patients. The combination of acute cellular and humoral rejection was found in 4 patients (5 biopsies). The PDGFBB level was measured at the same day as the biopsy was taken, and it was shown to be signifi cantly higher in patients with rejection (p = 0.02). Rejection frequency was signifi cantly higher in patients with high PDGF-BB level (≥2473.7 pg/ml, RR = 1.64 ± 0.23; 95% CI [1.03–2.61]). Rejection frequency increased to 2.11 ± 0.34 [95% CI [1.08–4.11]] in recipients with ST2 and PDGF-BB concentration higher than the median value. The highest predictive value for heart rejection can be reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2 (RR = 2.51 ± 0.38; 95% CI [1.18–5.3]).Conclusion. PDGF-BB has moderate predictive value for heart rejection. The highest predictive value for heart rejection was reached by a panel of three biomarkers: sCD40L, PlGF-1 and ST2

PILOT STUDY RESULTS OF THE INFLUENCE OF CITICOLINE AND PIRIBEDIL ON COGNITIVE FUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE AFTER CORONARY ARTERY BYPASS SURGERY

Aim. To reveal cognitive deficit after coronary artery bypass, the influence of citicoline, piribedil on the state of higher cerebral functions in the early and late periods after surgery.Material and methods. The study included 94 patients with ischemic heart disease. All patients were divided into 3 groups. Patients of the first group (n=30) were prescribed citicoline as a cerebral neuroprotective drug. Patients of the second group (n=32) had piribedil in addition to standard therapy. Patients of the control group (n=32) had only a standard treatment without any neuroprotective drugs. All patients underwent coronary artery bypass surgery. The cognitive function was assessed before, 10 days after and six months after coronary artery bypass.Results. Patients of group 1 and 2 had achieved pre-surgical levels of cognitive tests results 6 months after coronary artery bypass. The control group had achieved initial levels only in three tests: visual memory (immediate simulation; p=0.008), categorical association (p=0.002), clock drawing test (Wilcoxon test; p=0,005), while other indices were reduced in comparison with the initial ones.Conclusion. The obtained results allow considering the studied drugs as a protectors of cognitive function after surgery. Randomized controlled double-blind studies on large samples are needed to confirm these results.</p

The effectiveness of piribedil for the treatment of cognitive disorders in patients with coronary heart disease: results of six-month&#x0D; observation

Aim. The detection of cognitive deficiency after heart bypass surgery, the evaluation of the influence of piribedil on the higher cerebral function in the early postoperative period during the follow-up. Materials and methods. 64 patients with ischemic heart disease were examined. They were divided into two groups. Patients of the main group (n=32) were treated with pronoran (piribedil) at a daily dose of 50 mg for 3 months. 32 patients of the control group received standard therapy in the postoperative period. All patients had undergone heart bypass surgery. Cognitive functions were examined before operation, 10 days , three and six months after surgery. Results. Positive dynamics of all tested parameters was documented in the patients of the main group within 6 months after the onset of therapy. In control patients, cognitive disorders remained at the preoperative level based on the results of three tests. Conclusion. The positive results of piribedil therapy suggest that piribedil has positive effect on memory, attention and psychomotor activity of the patients</jats:p

PILOT STUDY RESULTS OF THE INFLUENCE OF CITICOLINE AND PIRIBEDIL ON COGNITIVE FUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE AFTER CORONARY ARTERY BYPASS SURGERY

Aim. To reveal cognitive deficit after coronary artery bypass, the influence of citicoline, piribedil on the state of higher cerebral functions in the early and late periods after surgery.Material and methods. The study included 94 patients with ischemic heart disease. All patients were divided into 3 groups. Patients of the first group (n=30) were prescribed citicoline as a cerebral neuroprotective drug. Patients of the second group (n=32) had piribedil in addition to standard therapy. Patients of the control group (n=32) had only a standard treatment without any neuroprotective drugs. All patients underwent coronary artery bypass surgery. The cognitive function was assessed before, 10 days after and six months after coronary artery bypass.Results. Patients of group 1 and 2 had achieved pre-surgical levels of cognitive tests results 6 months after coronary artery bypass. The control group had achieved initial levels only in three tests: visual memory (immediate simulation; p=0.008), categorical association (p=0.002), clock drawing test (Wilcoxon test; p=0,005), while other indices were reduced in comparison with the initial ones.Conclusion. The obtained results allow considering the studied drugs as a protectors of cognitive function after surgery. Randomized controlled double-blind studies on large samples are needed to confirm these results

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P = 0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P&lt;0.001). CONCLUSIONS Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; p interaction =0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; p interaction =0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen