In Search of Optimal Criteria for Iron Deficiency in CHF Patients. Post-hoc Analysis of the Study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)".

AIM: Comparative analysis of clinical, anamnestic, and laboratory and instrumental data of patients with chronic heart failure (CHF) and iron deficiency (ID) diagnosed according to the AHA/ESC/RSC criteria, and CHF patients diagnosed with ID based on decreased transferrin saturation (TSAT) ≤19.8% or serum iron (Fe) ≤13 µmol/l. MATERIAL AND METHODS: An additional analysis of the ID-CHF-RF study was performed. The analyzed population included 498 patients (198 women) with CHF. In addition to the ID criteria provided by the protocol (AHA/ESC/RSC criteria: ferritin <100 µg/l or ferritin from 100 to 299 µg/l and TSAT<20%), concentrations of ID biomarkers were assessed, which showed high sensitivity and specificity for the diagnosis of ID compared to the morphological picture of the bone marrow (TSAT<19.8% or Fe ≤13 µmol/l). Subgroups of patients with ID determined only by the AHA/ESC/RSC criteria, only by the TSAT≤19.8% and Fe ≤13 µmol/l criteria, and by both were analyzed. RESULTS: ID diagnosed by the AHA/ESC/RSC criteria was found in 83.1% of patients. The TSAT ≤19.8% and Fe ≤13 µmol/l criteria revealed ID in 74.5% of patients. In 341 patients (76.8%), ID was diagnosed using both criteria. Patients with ID diagnosed by the TSAT≤19.8% and Fe≤13 µmol/l criteria, compared with patients with ID diagnosed by the AHA/ESC/RKO criteria, had a 50% lower Fe (9.8 µmol/l vs. 19.4 µmol/l) and a higher incidence of anemia (43.3% vs. 23.3%) and diabetes mellitus (DM) (36.7% and 24.7%). Also, these patients had higher values of body mass index (BMI) and NT-proBNP concentration (2317 [1305;9092] vs. 1691 [709;3856] pg/ml), and lower LV EF values (41.5 [29.0;54.5]% vs. 45.0 [34.0;54.0]%), respectively. The most severe course of CHF and the greatest changes in laboratory tests associated with ID and anemia were observed in patients with ID determined by two criteria. Patients in this group were older, with a higher BMI, more frequent presence of atrial fibrillation, and higher NT-proBNP (4182 [1854;9341] pg/ml). CONCLUSION: Patients with isolated low ferritin are characterized by less severe clinical and functional impairment compared to patients with low TSAT or Fe. At the same time, patients with ferritin higher than 300 µg/l and low TSAT and/or Fe were characterized by very severe CHF and a low functional status, although this may not be related with ID. Thus, the use of the ferritin-based criteria of ID may lead to overdiagnosis of ID in some patients and, at the same time, miss some of the most "severe" patients who likely require the ID correction. Patients with ID who show a decrease in all three parameters are likely to benefit most from Fe supplementation. It is advisable to perform additional studies on the effect of Fe supplements on the course and prognosis of the disease in this cohort of patients.

Female and Male Phenotypes of Iron Deficiency in CHF. Additional analysis of the «The Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)¼ study.

Aim    To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods    An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results    ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC III increased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IV 13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion    Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.

[Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study].

Aim    To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods    Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results    83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion    The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

Cardioprotective potential of chronopharmacotherapy in patients with arterial hypertension who had a transient ischemic attack.

Aim    Analysis of the cardioprotective effectivity of chronopharmacotherapy in patients with arterial hypertension (AH) after transient ischemic attack (TIA).Material and methods    174 patients with AH and TIA were evaluated. All patients were randomized to three groups based on the dosing schedule of chronopharmacotherapy: group 1 (n=59), patients receiving indapamide retard 1.5 mg and valsartan 160 mg, both in the morning; group 2 (n=58), indapamide retard 1.5 mg in the morning and valsartan 160 mg in the evening; group 3 (n=57), indapamide retard 1.5 mg in the morning and valsartan 80 mg in the morning and evening. Echocardiography (EchoCG) (ALOKA SSD 2500, Japan) was performed for all patients at baseline and at 12 months of the treatment. Statistical analysis of results was performed with the Statistica 12.0 (StatSoftInc, USA) software.Results    Before the treatment, EchoCG parameters did not significantly differ between the patient groups. After 12 months of the treatment, positive changes in the end-systolic dimension (ESD), interventricular septal thickness (IVST), thickness of the left ventricular posterior wall (TLVPW), LV myocardial mass (LVMM), LVMM index (LVMMI), ejection fraction (EF), ratio of transmitral early peak flow velocity and late filling flow velocity (E/A), and isovolumetric velocity relaxation time (IVRT) were more pronounced in the group of sartan evening dosing (group 2) than in the group of sartan single morning dosing (group 1) (p<0.05). In group 3, the changes in ESD, IVST, TLVPW, LVMM, LVMMI, EF, E/A ratio, deceleration time (DT) of LV, and IVRT were significantly greater than those in group 1, whereas the dynamics of ESD, IVST, TLVPW, LVMM, LVMMI, E/A ratio, and DT were better in group 3 than in group 2 (p<0.05). In addition, a significantly greater number of patients with normalized LV geometry was registered in group 3 compared to groups 1 and 2 (p<0.05). The number of patients with normal LV diastolic function after the treatment was also significantly greater in group 3 than in group 1 (p<0.05) and comparable with group 2.Conclusion    The morning dosing of indapamide retard and the b.i.d. dosing of valsartan provided more pronounced beneficial changes in major EcoCG indexes and improvement of LV geometry and diastolic function than the sartan single dosing only in the morning or evening in combination with the diuretic.

[Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts' Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Arrhythmology Association].

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.

[The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange].

The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.

[Physical training in patients with chronic heart failure: level of involvement, as well as psychosocial, anamnestic and iatrogenic factors that determine the motivation to practice].

Introduction Physical exercise (PE) is a necessary part in the treatment of patients with chronic heart failure (CHF), which is stated in the European Society of Cardiology guidelines and the Russian Heart Failure Society guidelines. However, this type of non-drug treatment is still not sufficiently used in HF patients in Russia.Aim To study the current involvement of HF patients in PT and to describe psychosocial factors that influence the patients' willingness to exercise and potential barriers and motivations for PE.Methods This study was designed as an in-moment survey. Patients with CHF who visited clinics in 7 cities of the Russian Federation in 2018 as a part of European Heart Failure Awareness Days were provided with a self-administered questionnaire containing questions about their social and educational status, attitude to PT as a method of treatment, and factors motivating and demotivating them to participation in training sessions. The survey participants were also asked a question about their source of information about exercise in HF. Physicians filled in the items describing HF clinical manifestations (left ventricular ejection fraction (EF) and HF functional class (FC)). Code numbers were used for further identification of the participants and to protect their confidentiality. Statistical analysis was performed with the StatXcat-8 program. Limits of exact confidence intervals (CIs) were provided both for fractions and parameters of polynomial distribution. CI limits for differences and fractions were calculated using MOVER. Age was analyzed using the PAST program.Results The study included 560 patients with HF; 52 % of them were women (mean age, 64; 95 % CI: 63-65 years). Women were 3 years older than men (95 % CI: 1.3-4.9 years). 501 (89.5 %) patients had FC II-III; 265 (49 %) patients had HF with low EF. 350 (62 %) patients had comorbidities: 41.4 % of patients had diabetes mellitus and 25.4 % of patients had arthritis. Only 91 (17 %) patients reported exercising. Patients younger than 65 exercised significantly more frequently than older ones (odds ratio (OR), 1.7, 95 % CI: 1.0-2.7, р<0.001). Patients with higher education had better chances to be involved in PT or were more anxious to start training (OR, 2.7; 95 % CI: 1.6-4.7, р<0.001). The capability for influencing the disease was the major motivation for PT for both sexes. Probability of this answer was 48 % (95 % CI: 33-61) for men and 46 % (95 % CI: 29-63) for women. 62 % of patients indicated poor health as the major barrier for participation in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and only 50 % were informed about that by their physician.Conclusion The factors that positively influence the willingness to exercise include male sex, higher level of education, younger age, and better perception of the own health condition. 62 % of patients indicated poor health as the major barrier for participation in training. On the whole, the awareness of patients about PT benefits for health in HF was low. To our opinion, this was a serious factor of the extremely low involvement of patients in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and, furthermore, only 50 % of patients received this information from their physicians.

Antihypertensive and vasoprotective effectiveness of the chronopharmacotherapy in patients with arterial hypertension after acute cerebrovascular accident.

AIM: To evaluate the effectiveness of combined antihypertensive chronopharmacotherapy and estimate the daily blood pressure profle (BP) parameters, such as: stiffness of the vascular wall and central aortic pressure in patients with arterial hypertension (AH) who underwent transient ischemic atack (TIA) or ischemic stroke (IS). MATERIALS AND METHODS: 235 patients with hypertension who underwent acute cerebrovascular accident were examined. Tere were 116 patients with TIA and 119 with IS. All patients were randomized in 4 groups according to regimen of antihypertensive drugs combination. Te 1st group (n = 59) included patients with AH, who underwent TIA and received indapamide retard 1.5 mg and valsartan 160 mg in the morning regiment of drug therapy. Te 2nd group (n = 57) included patients with AH, who underwent TIA and received indapamide retard 1.5 mg in the morning and valsartan 80 mg twice a day (morning and evening). Te 3rd group (n = 47) included patients with AH, who underwent IS and received indapamide retard 1.5 mg and valsartan at a dose of 160 mg in the morning. Te 4th group (n = 56) included patients with AH, who underwent IS and received indapamide retard 1.5 mg in the morning and valsartan 80 mg twice a day (morning and evening). Ambulatory blood pressure monitoring (ABPM), central aortic pressure (CAP) measurement and vessel wall stiffness values were evaluated before treatment and afer 12 months of therapy. RESULTS: Before the start of combined antihypertensive chronopharmacotherapy, most of the parameters for ABPM, vessel wall stiffness values and CAP in groups 1 and 2, 3 and 4 were comparable. Achievement of the target level of BP afer 8 weeks of treatment, was signifcantly more ofen in groups with a double sartan therapy (group 2 and group 4) in compare with its single time application only in the morning hours (group 1 and group 3) (p<0.05). Statistically signifcant positive dynamics of the main values of the daily profle of blood pressure, stiffness of the vascular wall and central aortic pressure (p <0,05) were registered in all groups. However, more pronounced decline of main parameters of ABPM, stiffness of the vascular wall and central aortic pressure values were noted in group with double use sartan therapy in compare with single time sartan therapy in the morning time. (p <0.05). Signifcant positive dynamics of the main values of the ABPM, stiffness of the vascular wall and CAP were registered in patients who underwent IS and received double application sartan therapy (4th group) in compare with patients with TIA (2nd group) (p = 0.02). CONCLUSION: Double use sartan therapy, combined with a thiazide diuretics in patients, who underwent IS or TIA more ofen promotes to get target values of blood pressure, improve the main values of the ABPM, stiffness of the vascular wall and CAP in compare with single time sartan therapy in the morning time.

[Efficiency of triple antihypertensive therapy in patients with uncontrolled hypertension and depressive disorders]. / Éffektivnost' trekhkomponentnoi antigipertenzivnoi terapii u patsientov s nekontroliruemoi arterial'noi gipertoniei i depressivnymi rasstroistvami.

AIM: To evaluate the efficiency of triple antihypertensive therapy in patients with uncontrolled hypertension and depressive disorders (DD). MATERIAL AND METHODS: 153 patients with uncontrolled hypertension were examined, of whom 82 patients were diagnosed with mild and moderate DD. A combination of perindopril 10 mg/day, indapamide SR 1.5 mg/day, and amlodipine at an initial dose of 5 mg/day was given to patients with hypertension and DD. After 4 weeks of treatment, if target blood pressure (BP) levels could not be achieved, the dose of amlodipine was increased up to 10 mg/day. General clinical examination and 24-hour BP monitoring (BPM) were performed in all the patients at baseline and in the patients with DD also after 24 weeks of therapy. The traditional measures of the diurnal BP profile, as well as the parameters characterizing arterial stiffness and central aortic pressure (CAP) were estimated. RESULTS: After 8 weeks of therapy, target BP levels were recorded in 63 (76.8%) patients. After 24 weeks of treatment, the hypertensive patients with DD showed significant positive changes in all the investigated 24-hour BPM parameters and normalization of the diurnal BP profile in 65.1% of cases. During the treatment, there were significant decreases in pulse wave velocity, brachial arterial and aortic augmentation indices, aortic systolic and diastolic pressures, and mean aortic BP and an increase in the velocity of the reflected wave. CONCLUSION: Triple therapy, including perindopril, indapamide SR, and amlodipine, contributed to the achievement of target BP levels in the majority of hypertensive patients with DD, with significant positive changes in all 24-hour BPM parameters, optimization of the diurnal BP profile in most patients, clinically significant improvement of the parameters that characterize arterial stiffness and CAP.

[The Effectiveness of Combination Antihypertensive Therapy in Women With Hypothyroidism and the Metabolic Syndrome].

PURPOSE OF THE STUDY: Evaluating the effectiveness of the various options of combination antihypertensive therapy (AHT) in women with arterial hypertension (AH) and metabolic syndrome (MS) and hypothyroidism. MATERIAL AND METHODS: The study included 163 women with hypertension, metabolic syndrome, and hypothyroidism, the median age of 53.5 (48-60) years; in 73 (44.8%) women were diagnosed with subclinical hypothyroidism (SH), 90 (55.2%) - overt hypothyroidism (OH). Patients with both SH and OH, depending on the source of the heart rate (HR) was appointed as one of the following combination of AHT. If heart rate <75 beats/min, patients (n=100) received a combination of the dihydropyridine calcium antagonist (AA) amlodipine 5 mg/day, and angiotensin receptor blockers II (ARB) losartan 50 mg/day, with heart rate >75 beats/min (n=63) - a combination of amlodipine 5 mg/day and imidazoline receptor agonist (IRA) moxonidine 200 micrograms/day. The failure to achieve target blood pressure (BP) after 4 weeks of dose drugs doubled with subsequent evaluation of the effectiveness even after 4 weeks. At baseline and after 6 months of therapy, all patients underwent daily blood pressure monitoring (DBPM). RESULTS: At 8 weeks, the use of a combination of AA+ARB target BP level was registered in 26 (59%) of 44 women with SH and 34 (60.7%) of the 56 - OH. In the group of women who took the AA+IRA, after 8 weeks of the target blood pressure was observed in 24 (82.8%) of 29 patients with SH and 28 (82.4%) of 34 - to OH. Register the target blood pressure was observed significantly more frequently (p<0,05) when using a combination of AA+IRA compared with AA+ARBs as with SH and OH. As a result of the combination of DBPM AA and ARBs in patients with SH and OG provided a significant reduction in average daily, daytime and nighttime systolic and diastolic blood pressure (SBP and DBP), the time index of SBP and DBP during the day and night hours. The therapy of AA and IRA regardless of the severity of hypothyroidism, there was a significant improvement in all indicators DBPM: average daily, daytime and nighttime SBP and DBP, time index and variability in SBP and DBP during the day and at night. Furthermore, as in the SH and OH significantly more pronounced positive changes most DBPM parameters were recorded using IRA in combination with AA compared with a combination AA+ARB. Significant increase in the number of women with optimal BP daily profile "dipper" observed only when using amlodipine and moxonidine. CONCLUSION: In women with hypertension, hypothyroidism and MS, regardless of the severity of decline of thyroid function and combination of the dihydropyridine AA IRA had an advantage over the AA combination with ARBs, since most patients provided achieving target blood pressure and clinically significant positive impact on BPM indicators. The results can be used in selecting the optimal AHT in patients with hypertension, MS, and the manifest subclinical hypothyroidism.