RESUMO
AIM: Identification of interleukin-6 (IL-6) signaling pathways in patients with chronic heart failure (CHF). MATERIAL AND METHODS: The diversity of IL-6 effects is due to the presence of classical signaling and trans-signaling pathways. The study included 164 patients with CHF hospitalized for acute decompensated heart failure (ADHF), of which 129 had reduced left ventricular ejection fraction (HFrEF), and 35 had preserved ejection fraction (HFpEF). Blood concentrations of IL-6, soluble IL-6 receptor (sIL-6R), soluble transducer protein gp130 (sgp130), and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Patients with HFpEF had lower concentrations of IL-6 (6.15 [2.78, 10.65] pg/ml) and hsCRP (11.27 [5.84, 24.40] mg/ml) than patients with HFrEF (9.20 [4.70; 15.62] pg/ml and 17.23 [8.70; 34.51 mg/ml], respectively). In contrast, concentrations of rIL-6R were higher in HFpEF (59.06 [40.00; 75.85] ng/ml) than in HFrEF (49.15 [38.20; 64.89] ng/ml). Concentrations of sgp130 were not significantly different. In patients with HFrEF, positive correlations were found between the concentrations of IL-6 and hsCRP, IL-6 and rIL-6R, and IL-6 and sgp130, while in patients with HFpEF, there was a correlation only between IL-6 and hsCRP, which appeared stronger than in patients with HFrEF (r=0.698; p<0.001 and r=0.297; p<0.05, respectively). CONCLUSION: Classical IL-6 signaling and trans-signaling are expressed to different degrees in patients with HFrEF and HFpEF in ADHF. The results of the study supplement the existing knowledge about the pathogenesis of inflammation in CHF and may contribute to the development of new methods and approaches to the treatment of the disease.
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Insuficiência Cardíaca , Humanos , Proteína C-Reativa , Receptor gp130 de Citocina , Insuficiência Cardíaca/diagnóstico , Interleucina-6 , Volume Sistólico , Função Ventricular EsquerdaRESUMO
AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14âmm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14âmm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.
Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Hipertrofia Ventricular Esquerda , Idoso , Feminino , Humanos , Masculino , Neuropatias Amiloides Familiares/epidemiologia , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Cardiomiopatias/epidemiologia , Ecocardiografia , Hipertrofia Ventricular Esquerda/epidemiologia , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Prevalência , Federação Russa/epidemiologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
AIM: To evaluate the impact of a decrease in glomerular filtration rate (GFR) on the prognosis of patients with chronic heart failure (CHF), to analyze real clinical practice regarding the frequency of prescribing pathogenetic therapy for CHF, achieving target dosages depending on the gradation of GFR in patients included in the CHF Register of the Tyumen region. MATERIALS AND METHODS: The analysis included medical data of 4077 patients (1662 men and 2415 women) with NYHA class I-IV CHF who underwent examination and treatment in medical organizations of the Tyumen region for the period from January 2020 to May 2023. Criteria for inclusion in the register: proven heart failure. Chronic kidney disease (CKD) was assessed by GFR calculated using the CKD-EPI formula (ml/min/1.73 m2). The primary end point was defined as death from all causes. RESULTS: GFR<60 ml/min/1.73 m2 was recorded in 34.6% of patients, more common in women (40.2 and 26.6%, respectively; p<0.001). When dividing patients into phenotypes according to LVEF, no statistically significant differences were found in the distribution of patients according to GFR. In patients with HFrEF and HFpEF GFR<45 ml/min/1.73 m2 was associated with an increased risk of meeting the endpoint. Analysis of prescribed pathogenetic therapy showed that in patients with HFrEF, the frequency of prescription of ACE inhibitors, â-blockers and MRA decreased (p=0.023, 006 and 0.01, respectively), and ARNI, on the contrary, increased with a decrease in GFR (p=0.026). In patients with HFpEF, a similar trend towards a decrease in the frequency of prescription of ACEIs and MCBs with a decrease in GFR (p<0.001) remained, but it was compensated by an inversely proportional increase in the frequency of prescription of ARBs (p<0.001). 100% of the target dosage is achieved in more than 90% of patients taking MRA across the entire LVEF range. While for â-blockers and ARNI/ACE/ARB the percentage of patients receiving the full therapeutic dosage of drugs is significantly lower. When analyzing target dosages of pathogenetic drugs, gradations of achieved doses were distributed evenly throughout the entire range of GFR. CONCLUSION: GFR<60 ml/min/1.73 m2 occurs in every 3 patients with CHF across the entire range of LVEF. A decrease in GFR worsens the prognosis of patients with both HFrEF and HFpEF, increasing in direct proportion with the severity of the stage of CKD. Inclusion of patients in the monitoring program within the framework of the CHF service allows the treatment to be significantly brought closer to optimal drug therapy, at the same time, certain efforts are required to overcome difficulties with titration to target dosages.
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Taxa de Filtração Glomerular , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/epidemiologia , Prognóstico , Pessoa de Meia-Idade , Idoso , Federação Russa/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Sistema de Registros , Volume Sistólico/fisiologiaRESUMO
The features of IL-6 trans-signaling were studied in patients with heart failure with reduced (n=74) and preserved (n=31) ejection fraction (EF) during acute decompensation of HF (ADHF) and after 1 year. Patients with ADHF with reduced EF demonstrated higher levels of IL-6 and soluble glycoprotein 130 in comparison with those in patients with preserved EF: 10.18 (7.07; 16.14) pg/ml vs 6.35 (3.52; 11.00) pg/ml and 543.46 (455.37; 634.43) ng/ml vs 498.50 (408.16; 632.23) ng/ml, respectively. The levels of soluble IL-6 receptor little differed in these groups: 57.82 (47.55; 79.85) ng/ml vs 61.30 (44.97; 78.08) ng/ml. After 1 year, the levels of IL-6 in HF patients with reduced EF significantly decreased (5.36 (3.35; 8.35) pg/ml), while in patients with preserved EF, the decrease in this parameter was less pronounced (5.86 (4.05; 7.32) pg/ml), and the difference between groups disappeared. The levels of soluble glycoprotein 130 increased in both groups: 448.06 (357.74; 550.67) ng/ml vs 385.35 (344.29; 523.72) ng/ml. It should be noted that after 1 year (in stable patients), the levels of soluble IL-6 receptor increased in both groups: 65.75 (54.84; 75.39) ng/ml vs 70.81 (57.51; 82.25) ng/ml. Thus, despite the high levels of IL-6 in HF patients with reduced EF, the potential limiting IL-6 trans-signaling in these patients is higher than in patients with preserved EF.
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Insuficiência Cardíaca , Interleucina-6 , Humanos , Volume Sistólico , Receptor gp130 de Citocina , Doença CrônicaRESUMO
The interaction of different scientific schools with each other often is very difficult due to the existing disagreements. The journal "Therapeutic Archive" throughout its activity is a unique platform for their intensive and fruitful interaction, and the editors-in-chief of the journal represent almost all major schools of internal medicine.
Assuntos
Medicina Interna , Instituições Acadêmicas , Federação RussaRESUMO
Heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction are associated with significant morbidity and mortality, as well as growing economic burden. This review describes recent studies on the use of sacubitril/valsartan in heart failure patients with mildly reduced or preserved ejection fraction.
Assuntos
Insuficiência Cardíaca , Tetrazóis , Humanos , Volume Sistólico , Antagonistas de Receptores de Angiotensina/farmacologia , Valsartana , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Combinação de MedicamentosRESUMO
Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.
Assuntos
Neuropatias Amiloides Familiares , Hiperemia , Humanos , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/complicações , Hiperemia/complicações , Mutação , Fenótipo , Pré-Albumina/genéticaRESUMO
AIM: To evaluate and compare the accuracy of volemic status determination by remote dielectric sensing with computed tomography (CT) in patients with acute decompensated heart failure. MATERIALS AND METHODS: In 28 patients volemic status was determined by ReDS (remote dielectric sensing), chest computed tomography (CCT), and chest X-ray twice during hospitalization (the day of admission and the day of discharge from the hospital). The ReDS measurements were then compared with CT data using software that allows the use of semi-automated tools to determine mean lung density (MLD). MLD results from Hounsfield Units [HU] were then converted to fluid levels (FU%), allowing them to be compared with ReDS values. In addition, to assess the effect of physical activity on the dynamics of pulmonary stasis there was performed 6-minute walk test (6MWT) followed by determination of volumic status by ReDS method. RESULTS: Correlation analysis revealed an average direct significant correlation (r=+0,5; p=0.001) between the CCT and ReDS data. Hypervolemia indexes according to the CCT revealed statistically significant decrease in the dynamics, which was also reflected in the ReDS index decrease. Lung fluid content according to ReDS averaged 38.2±4.6% on admission, and 34.5±3.9% on discharge (p=0.005). According to CT scan of the CCT, MLD at admission was 23.03±3.9%, at discharge 19.6±3.3% (p=0.003). The positive dynamics of the study methods was also reflected in the positive dynamics of NT-proBNP, which decreased by 46%. In the analysis of ReDS data before and after exercise, there was an increase in ReDS value after the performed 6MWT and it was 35.09±3.9% compared with the initial value of 34.5±3.9%. A strong direct significant correlation (r=+0.7; p=0.0001) was found between the ReDS before and after 6MWT at discharge.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Pulmão/diagnóstico por imagem , Hospitalização , Tomografia Computadorizada por Raios XRESUMO
AIM: To estimate the cost-effectiveness of dapagliflozin across the range of ejection fraction in patients with heart failure (HF) in Russian Federation. MATERIALS AND METHODS: Cost-effectiveness model was developed for estimate the use of dapagliflozin as part of standard therapy in patients with HF regardless of ejection fraction is unknown. The calculation of costs was carried out in a mathematical model adapted to the conditions of Russian healthcare system by using Russian costs inputs and patient population characteristics. RESULTS: In the model, dapagliflozin therapy yielded a mean of 0.209 additional life-years compared with standard of care in 10 years horizon. The incremental cost of 1 additional life-year was 665,715 RUB, which does not exceed the threshold of willingness to pay 2,235,202 RUB. CONCLUSION: Thus, the intensification of chronic HF therapy with dapagliflozin is cost effective. The use of dapagliflozin in a cohort of 1000 target patients over 10 years will avoid 146 hospitalizations and 39 emergency visits due to HF, as well as prevent 32 deaths from cardiovascular diseases.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Humanos , Volume Sistólico , Insuficiência Cardíaca/tratamento farmacológico , Doença Crônica , Federação Russa/epidemiologiaRESUMO
The article presents a clinical case describing a complex differential diagnosis of cardiac amyloidosis types and verification of the diagnosis of AL-amyloidosis.
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Neuropatias Amiloides Familiares , Humanos , Neuropatias Amiloides Familiares/diagnóstico , Diagnóstico DiferencialRESUMO
The annual mortality of patients with clinically pronounced symptoms of chronic heart failure in the Russian Federation reaches 26-29%, i.e., from 880 to 986 thousand patients with heart failure die in the country in one year, which is comparable to the population of a large city. Providing care for patients with heart failure places a heavy burden on the country's health care system, making a significant contribution to mortality rates, hospitalization rates, including readmissions, which in turn requires considerable costs. The article presents an overview of registry studies that are devoted to assessing the effectiveness of diagnostics, the completeness of examinations, as well as the adequacy of ongoing drug treatment.
Assuntos
Insuficiência Cardíaca , Hospitalização , Humanos , Doença Crônica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Federação Russa/epidemiologiaRESUMO
Plasma levels of meprin A, IL-6, and IL-18 were measured in 68 patients with acute decompensated heart failure at the time of admission to the hospital and after 1 year. The patients were assigned to groups depending on renal function disorder which was assessed by glomerular filtration rate (GFR). During hospital stay, the plasma levels of meprin A in patients with normal GFR (≥90 ml/min/1.73 m2) were considerably higher than in patients with reduced GFR (<90 ml/min/1.73 m2): 1.80 (0.86; 2.65) and 1.04 (0.56; 1.60) ng/ml, respectively. The levels of IL-6 and IL-18 did not differ significantly. After 1 year, plasma levels of meprin A and interleukins markedly decreased in patients with normal GFR (0.33 (0.20; 0.86) ng/ml) and remained high in patients with reduced GFR (0.92 (0.39; 1.33) ng/ml). Thus, the dynamics of meprin A levels in patients with acute decompensated heart failure depends on functional state of the kidneys, which may affect the course of heart failure.
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Insuficiência Cardíaca , Rim , Metaloendopeptidases , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Interleucina-18/sangue , Interleucina-6/sangue , Metaloendopeptidases/sangue , Admissão do Paciente , Tempo de Internação , Taxa de Filtração Glomerular , Rim/fisiopatologiaRESUMO
Are presented the key aspects of the management of patients with acute decompensation of heart failure leading to improved clinical outcomes. Are described the existing problems and possible solutions.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologiaRESUMO
The current worldwide prevalence of heart failure is growing, while its combination with cardiovascular and other conditions determines a poor prognosis in these patients. Furthermore, acute decompensated heart failure is associated with a low survival rate mostly caused by target organ damage. The effects of early administration of SGLT2 inhibitors on renal function in patients with acute decompensated heart failure are being studied to determine the possibility of improving response to treatment, as well as partial or complete recovery of renal function. The goal of the review was to synthesize currently available evidence for the use of SGLT2 inhibitors in patients with acute decompensated heart failure. A systematic search for studies published from 2018 to 2021 and their analysis was carried out in the following databases: Web of Science, Scopus, PubMed/MEDLINE.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca/complicaçõesRESUMO
The article summarizes the current experience of the nuclear medicine department of the Chazov National Medical Research Center of Cardiology in the implementation of myocardium scintigraphy with 99mTc-pyrophosphate with the differential diagnosis of the types of cardiac amyloidosis. Causes of false-positive, equivocal and non-diagnostic results, are analyzed. Possible ways to eliminate mistakes, including by modifying protocols of planar and tomographic research and optimizing the whole diagnostic algorithm for amyloidosis of the heart, are discussed.
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Amiloidose , Cardiomiopatias , Imagem de Perfusão do Miocárdio , Humanos , Pirofosfato de Tecnécio Tc 99m , Difosfatos , Cardiomiopatias/diagnóstico por imagem , Cintilografia , Amiloidose/diagnóstico por imagem , AlgoritmosRESUMO
This paper summarizes the data from updated international protocols and guidelines for diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). The invasive and non-invasive diagnosis techniques and their combinations are briefly reviewed; the evidentiary foundations for each diagnostic option and tool are analyzed. The paper describes a customized algorithm for sequential diagnosis and differential diagnosis of patients with suspected ATTR-CM with allowance for the combination of clinical signs and diagnostic findings. Along with the awareness of primary care providers about the red flags of the disease and visualization criteria, as well as providing information to the patients about the possibility of performing therapy of ATTR amyloidosis and the risks of delayed diagnosis, the proposed algorithm enables timely patient routing and prescribing specific treatment.
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Amiloidose , Cardiomiopatias , Humanos , Pré-Albumina , Amiloidose/diagnóstico , Amiloidose/terapia , Algoritmos , Diagnóstico Diferencial , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/terapiaRESUMO
Prevalence of chronic heart failure (CHF) is continuously growing and is associated with increased incidence of hospitalizations, morbidity and mortality. Furthermore, the increase in the number of rehospitalizations results in greater expenses and worsening of quality of life. In order to decrease the number of unscheduled hospitalizations and the death rate, the outpatient care should be improved, which can be achieved by using telemedical technologies. The aim of this review was collection and analysis of currently available information about the use of telemonitoring for patients with CHF. A systematic search and analysis of reports published from 2010 through 2020 in Web of Science, Scopus, and PubMed/MEDLINE databases was performed.
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Insuficiência Cardíaca , Telemedicina , Doença Crônica , Insuficiência Cardíaca/diagnóstico , Hospitalização , Humanos , Qualidade de VidaRESUMO
AIM: To evaluate the prognostic impact of serum uric acid (SUA) on clinical outcomes in patients with acute decompensated heart failure, as well as identify the correlation between hyperuricemia and renal function and diuretic resistance in these patients. MATERIALS AND METHODS: The study included 175 patients (125 men and 50 women) with NYHA class IIIV acute decompensated heart failure. Median age was 64 (5675) years. The Information regarding the survival was obtained 3 years after the admission by telephone calls. RESULTS: 57 patients reached the end point (death from all causes); therefore, all patients were divided into groups: "alive", "dead". The SUA levels did not differ in the groups. The only significant difference in the studied parameters was the estimated glomerular filtration rate (eGFR), which was significantly higher in the "alive" group [70.5 (52.894) and 56 (4079), respectively; p=0.006]. A moderate negative correlation was found between SUA levels and eGFR in the correlation analysis (r=-0.313, p0.001). A comparative analysis showed, that SUA level on admission was significantly higher in patients who subsequently received increased doses of diuretics than in patients with a satisfactory response to standard doses of diuretics [567.8 (479.6791.9) and 512 (422.4619.4), respectively; p=0.011]. Also, higher eGFR level on admission was observed in patients from the normal SUA level group than in patients from the hyperuricemia group [94 (74.5101.5) and 63 (48.881.3), respectively; p=0.002]. CONCLUSION: We found no significant differences in the uric acid level in patients who reached the end point and those who did not reach it during the three-year follow-up. However, the found correlation between uric acid levels and diuretic resistance calls for further research.
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Insuficiência Cardíaca , Hiperuricemia , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Ácido Úrico , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Prognóstico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Taxa de Filtração Glomerular , Diuréticos/uso terapêutico , Fatores de RiscoRESUMO
Systemic inflammation is characterized by the induction of pro-inflammatory cytokines, the increased level of which in the blood of patients with chronic heart failure (CHF) correlates with unfavorable clinical outcomes. However, it is unclear whether pro-inflammatory cytokines are the cause or the consequence of the disease progression. CHF with preserved ejection fraction and CHF with reduced ejection fraction demonstrate different inflammatory features, which suggests different degrees of pro-inflammatory pathway activation. The review deals with participation of pro-inflammatory cytokines in pathophysiological processes of CHF development, emphasizing the role of interleukin-6 activation and the effects of accompanying diseases on the course of systemic inflammation. The search for new approaches to prevention and therapy of CHF remains actual. The review presents the results of clinical trials of targeted anti-cytokine therapy which have revealed difficulties in controlling inflammation under the conditions of CHF. Identification of specific pro-inflammatory pathways in CHF pathogenesis will allow one to control inflammatory cascades, thus providing a prospective therapeutic strategy.
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Citocinas , Insuficiência Cardíaca , Humanos , Interleucina-6 , Doença Crônica , Inflamação/metabolismoRESUMO
AIM: To study the effect of cardiac contractility modulation on reverse remodeling and myocardial function in patients with chronic heart failure (HF) according to echocardiography (EchoCG). MATERIALS AND METHODS: In a group of 40 patients with a combination of chronic HF and atrial fibrillation (AF), the dynamics of standard EchoCG parameters and the effectiveness of myocardial work of the left ventricle (LV) against the background of 12-month therapy of cardiac contractility modulation (CCM) were analyzed. RESULTS: The results obtained indicate a statistically significant positive effect of CCM on LV remodeling parameters and the effectiveness of myocardial work according to EchoCG. CONCLUSION: Transthoracic echocardiography is the main imaging method and provides great opportunities for evaluating the effectiveness of HF treatment, including non-drug methods such as CCM. Evaluation of LV myocardial function in patients with HF and implanted CCM devices is a promising scientific and practical research method.