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.

[Prevalence and clinical associations of iron deficiency in patients with decompensated heart failure, depending on the diagnostic criteria used for iron deficiency].

AIM: To compare the frequency of iron deficiency (ID) in patients with decompensated heart failure (HF), defined by international guideline criterion ferritin 100 ng/ml or ferritin from 100 to 299 ng/ml with TSAT20% (criterion A) and by bone marrow biopsy criterion TSAT19.8% and serum iron 13 mol/l (criterion B); to evaluate the effect of ID, diagnosed on the basis of different ID criteria, on NT pro-BNP, sST2, CRP levels and New York Heart Association (NYHA) functional classes (FC) distribution between groups with ID and without ID. MATERIALS AND METHODS: The study included 223 patients (median age 73 [65; 82] years, 58% males) who were hospitalized to V.V. Vinogradov Moscow City Clinical Hospital No. 64 with decompensated HF. All patients underwent a standard physiological examination, laboratory and instrumental studies, including determination of NT-proBNP, sST2, CRP, and ferrokinetic parameters (serum iron, transferrin, ferritin). TSAT was calculated as: serum iron / transferrin 3.98. NYHA FC was determined according to Heart Failure Severity Rating Scale score. All patients underwent echocardiography to assess the ejection fraction of the left ventricle. RESULTS: According to criterion A ID was detected in 89% (n=199) of patients. There were no significant differences between levels of CRP, NT-proBNP and sST2. According to criterion B ID was detected in 70% (n=156) of patients. In the ID group, higher levels of CRP (15.1 mg/l vs 6.2 mg/l, p0.001), NT-proBNP (5422 pg/ml vs 2380 pg/ml, p0.001) and sST2 (59.6 ng/ml vs 42 ng/ml, p=0.02) were detected. Intravenous FCM admission according to current international guidelines (diagnosis of ID according to criterion A) is recommended to 57% of patients included in this study. Both methods formed groups with ID, in which patients had higher NYHA FC compared to groups without ID. According to current clinical guidelines, iron deficiency should be assessed according to method 1. More than half of patients (57, n=127) have indications for intravenous FCM to reduce risk of HF hospitalizations. CONCLUSION: The frequency of ID in patients with decompensated heart failure varies from 70 to 89% depending on the criterion used to diagnose ID, but in any case, remains high. Intravenous FCM should be prescribed in 57% (n=127) of patients. Criterion B, validated against the gold standard of diagnostics, unlike criterion A, makes it possible to form groups of patients with ID and without ID, significantly differing in CRP, NT-proBNP, and sST2 levels.

[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.

Prognostic Value of Admission-to-Discharge Change in Integral Congestion Assessment for Predicting Adverse Outcomes in Patients with Decompensated Heart Failure.

This study was performed to evaluate the prognostic value of relative changes from admission to discharge (Δ%) of integrated congestion assessment to predict adverse outcomes in patients with irreversible heart failure (HF) during a one-year follow-up. The study included 122 patients (60% males, median age of 69 years) with decompensated HF. Most of the patients (92%) had a history of arterial hypertension, 53.3% had coronary heart disease, and 40.2% had type 2 diabetes mellitus. All patients underwent assessments, including NT-proBNP, lung ultrasound (LUS) B-line score, liver stiffness by transient elastography, and resistance and reactance by bioimpedance vector analysis (BIVA). The assessments were performed at admission and discharge, and a relative change from admission (delta percentage, Δ%) was calculated. Long-term clinical outcomes were assessed by a structured interview conducted 1, 3, 6, and 12 months after discharge. The cut-offs for the occurrence of the endpoint events were Δ% NT-proBNP of ≥ -25, Δ% liver stiffness of ≥ -44, Δ% B-line score on lung ultrasound of ≥ -73, Δ% BIVA resistance of ≤ 18, and Δ% BIVA reactance of ≤ 40. It was revealed that 55% of endpoint events, including 22 (18%) deaths and 33 (27%) readmissions, occurred within a median of 74 days (interquartile range: 33-147). Patients with an endpoint event had significantly worse values of all studied parameters in contrast to patients without it. There was a significant direct association between Δ% NT-proBNP and Δ% B-lines (r=0.18; P=0.04), and a highly reliable inverse association was observed between Δ% liver stiffness and Δ% BIVA reactance (r=-0.4; P<0.001). No significant associations were found between the other parameters. Univariate Cox regression analysis demonstrated the independent prognostic value of all congestion markers under study (NT-proBNP, LUS B-lines, liver stiffness, and BIVA reactance) for predicting the combined endpoint. Multivariate Cox regression analysis confirmed the independent prognostic value in predicting the risk of endpoint event for the following parameters: NT-proBNP (hazard rate [HR] 2.5, P=0.001), liver stiffness (HR 2.3, P=0.012), LUS B-line score (HR 2.2, P=0.008). However, it did not find any significant prognostic value for BIVA resistance and reactance. The relative admission-to-discharge change in the integral assessment of congestion had a prognostic value for predicting the risk of adverse outcomes (all-cause mortality and readmission rate) in patients with decompensated HF during a one-year follow-up.