Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

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 ≥14 mm. 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 ≥14 mm, 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.

Interleukin 6 Signalling in Heart Failure With Preserved and Reduced Ejection Fraction.

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.

[Difficulties in differential diagnosis of the AL- and ATTR-cardiac amyloidosis. Case report].

The article presents a clinical case describing a complex differential diagnosis of cardiac amyloidosis types and verification of the diagnosis of AL-amyloidosis.

[A rare variant in the TTR gene (p.E112K) is associated with systemic amyloidosis and a new symptom - skin hyperemia in response to ethanol intake: family segregation analysis, literature review, and a clinical case. Case report].

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.

Dynamics of the Levels of Interleukin 6, Its Soluble Receptor, and Soluble Glycoprotein 130 in Patients with Chronic Heart Failure and Preserved or Reduced Ejection Fraction.

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.

Meprin A in Patients with Acute Decompensation of Heart Failure.

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.

[Myocardial scintigraphy with 99mTc-pyrophosphate in the diagnosis of cardiac amyloidosis: place in the diagnostic algorithm, features of the implementation and interpretation of the study].

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.

[Practical guidelines for the diagnosis and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM or transthyretin cardiac amyloidosis)].

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.

[Pro-inflammatory cytokines in chronic cardiac failure: state of problem].

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.

[Experience with tafamidis in a patient with transthyretin amyloidosis].

Transthyretin amyloidosis (ATTR) is a threatening and severe genetic disease characterized by damages to organs and systems caused by a pathological protein transthyretin produced in the liver. Clinical manifestations of this disease vary from injuries of the nervous system to injuries of the cardiovascular system. Prognosis for ATTR-amyloidosis remains unfavorable. The absence of pathognomonic symptoms complicates diagnostics of this disease, which tends to simulate other conditions. At present, medicines exist, which are pathogenetic in the treatment of ATTR-amyloidosis. The article describes a clinical case of ATTR-amyloidosis with primary heart injury complicated with functional class III chronic heart failure during the tafamidis treatment.

[The effect of angiotensin receptors and neprilysin inhibitors on myocardial remodeling in patients with chronic heart failure and atrial fibrillation].

AIM: To evaluate the effect of angiotensin-neprilysin receptor inhibitors on myocardial remodeling in patients with chronic heart failure and atrial fibrillation. MATERIALS AND METHODS: We studied dynamics of the parameters of ultrasound structural and functional parameters of the left atrium and left ventricle of the heart was during 3-month therapy with sacubitryl-valsartan in a group of 15 patients with a combination of chronic heart failure due to dilated and paroxysmal paroxysmal forms of atrial fibrillation. RESULTS: Showed a statistically significant positive effect of the use of angiotensin receptors and neprilysin inhibitors on the parameters of remodeling of the left atrium (according to transthoracic and transesophageal echocardiography), left ventricle, as well as levels of natriuretic peptides ANP and NT-pro-BNP. CONCLUSION: The use of ARNI may be promising in terms of treatment and prevention of AF in patients with heart failure.

Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure.

AIM: To study the possibilities of previously diagnosing acute renal damage in patients with acute decompensation of chronic heart failure with reduced systolic function using biomarkers of acute renal injury. MATERIALS AND METHODS: The study included 60 patients (62.0±11.1 years) with HADS (BNP >500 pg/ml) and a reduced left ventricular ejection fraction (LV 27.05% [23.25; 32.75], c FC III-IV NYHA). The level of creatinine, urea, uric acid, albumin in serum was determined in all patients, as well as a number of biomarkers: lipocalin associated with neutrophil gelatinase (NGAL) and cystatin C (CysC) in serum; kidney damage molecule-1 (KIM-1) and angiotensinogen (AGT) in the urine. RESULTS: AKI is determined based on changes in serum creatinine concentration or diuresis value. The results obtained indicate a high specificity and sensitivity of the use of biomarkers for the diagnosis of AKI in patients with ADHF. NGAL AUC - 0.833 (p<0.001), Se - 82.8%, Sp - 4.2%. CysC AUC - 0.823 (p<0.001), Se - 79.3%, Sp - 74.2%. KIM-1 AUC - 0.782 (p<0.001), Se - 75.9%, Sp - 74.2%. AGT AUC - 0.829 (p<0.001), Se - 82.8%, Sp - 77.4%. In a multifactorial regression analysis, it was found that with NGAL greater than 157.35 ng/ml, the risk of AKI increases 13.1 times (95% CI 1.365-126.431), with an increase in KIM-1, the risk of the development of AKI increases 20.6 times (95% CI 1.802-235.524), and with an increase in AGT more than 14.31 leng/ml, the risk of AKI increases 32.8 times (95% CI 2.752-390.110). CONCLUSION: Acute kidney injury develops in 48.3% of patients hospitalized with acute decompensation of chronic heart failure. Patients with acute decompensation of chronic heart failure and AKI have significantly higher serum NGAL and CysC, KIM-1 and AGT values in the urine compared with patients without impairing renal function. These biomarkers can serve both for the early diagnosis of acute kidney damage and the prediction of AKI in patients with acute decompensation of chronic heart failure.

[Neutrophil gelatinase-associated lipocalin for early diagnosis of acute kidney injury in patients with acute decompensated heart failure].

BACKGROUND: the incidence of acute kidney injury (AKI) is high in patients with acute decompensated heart failure (ADHF) and is linked with increased morbidity and mortality rates. Predictive biomarkers of AKI could allow improve outcomes in AKI. PURPOSE: to evaluate the value of serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations for early diagnosis of AKI in patients with ADHF with left ventricular (LV) systolic function. METHODS: we enrolled 60 men (average age was 62.0±11.1 years) hospitalized with ADHF with reduced LV systolic function (LV ejection fraction (LVEF).

[Myocardial metastasis of Wilms' tumor as a cause of focal electrocardiographic changes].

Nephroblastoma (Wilms' tumor) is an embryonic tumor, an adenomyosarcoma that is casuistically rarely encountered in adults. It most commonly develops in children aged 1 to 5 years. This type of malignancy does not usually spread to the myocardium. The paper presents a clinical case of Wilms' tumor in an adult female patient with a solitary metastasis in the heart.

[Polymorphism of ACE, angiotensin II, NO-synthase, estrogen receptor genes and gender differences in their effects on development of cardiovascular pathology].

Genetic factors determine resistance or susceptibility to development of many cardiovascular diseases. The study of polymorphisms of gene candidayes is a perpective approach in detection of risk and prognosis of outcomes of cardiovascular diseases. Most studied with the help of proven base genes are: ACE gene, angiotensin II gene, NO synthase gene, and estrogen receptor gene. Polymorphism of candidate genes has various clinical consequences in men and women. Despite small number of data devoted to gender differences our work sums up existing results of studies of polymorphisms of above mentioned 4 genes with consideration of gender peculiarities.