Vol 96, No 7 (2024): VARIO

Cover Page

Full Issue

Editorial

Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors

Blinova N.V., Ilovayskaya I.A., Chikhladze N.M., Lugovskaya A.Y., Britvin T.A., Gurevich L.E., Nefedova L.N., Shikina V.E., Chazova I.E.

Abstract

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2–8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2–0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

Terapevticheskii arkhiv. 2024;96(7):645-658
pages 645-658 views

Original articles

Glucose metabolism disorders and hypoglycemic therapy in patients hospitalized for elective lower limb arthroplasty: a prospective, single-center, real-world study

Okisheva E.A., Trushina O.Y., Mamaeva M.M., Redyanova E.A., Zhazhieva A.A., Chasova I.D., Panferov A.S., Bogdanov M.M., Lychagin A.V., Fomin V.V.

Abstract

Aim. To assess the incidence of glucose metabolism disorders, administered hypoglycemic therapy and its effectiveness in a cohort of patients with previously diagnosed diabetes mellitus (DM) hospitalized for scheduled lower limb joint arthroplasty.

Materials and methods. The study included 502 patients. Medical history, information about previously diagnosed DM and prescribed hypoglycemic therapy were collected in all patients according to medical documentation, as well as according to the patients’ survey. Within the preoperative examination, the glucose level was measured, and in patients with previously diagnosed diabetes, measuremaent of the HbA1c level was recommended.

Results. The study population included 180 (35.9%) males and 322 females (64.1%). Among them, 99 (19.7%) patients had disorders of glucose metabolism [type 1 diabetes – 1 (0.2%) patient, type 2 diabetes – 90 (17.9%) patients, impaired glucose tolerance (IGT) – 8 (1.6%) patients]. In 8 patients, type 2 diabetes was newly diagnosed during the preoperative examination. HbA1c was measured before hospitalization in 26 patients with diabetes, the mean level was 7.0±1.4%. Regarding the analysis of hypoglycemic therapy, almost half of the patients with DM – 47 (47.5%) – received metformin monotherapy, 8 patients with IGT and 8 patients with newly diagnosed DM did not receive any drug therapy. Target glycemic levels during therapy were achieved in 36 (36.4%) patients, and target HbA1c levels were achieved in 21 patients.

Conclusion. The cohort of patients hospitalized for elective lower limb joint arthroplasty is characterized by a relatively high incidence of glucose metabolism disorders, and in some patients, DM was newly diagnosed during the preoperative examination. Metformin is most often used as hypoglycemic therapy, and the target values of glycemia during treatment were achieved in less than half of the patients. The monitoring of the level of glycated hemoglobin is low and requires additional population analysis in order to determine the causes and optimize the strategy of patient management.

Terapevticheskii arkhiv. 2024;96(7):659-665
pages 659-665 views

Chronic kidney disease and chronic heart failure: impact on prognosis and choice of pathogenetic therapy

Mezhonov E.M., Reitblat O.M., Vyalkina Y.A., Airapetian A.A., Lazareva N.V., Ageev F.T., Blankova Z.N., Svirida O.N., Prints Y.S., Zhirov I.V., Tereshchenko S.N., Boytsov S.A.

Abstract

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.

Terapevticheskii arkhiv. 2024;96(7):666-674
pages 666-674 views

Improvement of the technique of positioning the endocardial electrodes of the cardiac contractility modulation device in patients with CHF with reduced ejection fraction and atrial fibrillation

Safiullina A.A., Uskach T.M., Sapelnikov O.V., Saidova M.A., Ansheles A.A., Sergienko V.B., Amanatova V.A., Grishin I.R., Cherkashin D.I., Akchurin R.S., Tereschenko S.N.

Abstract

Aim. To evaluate the efficacy and safety of the advanced technique for positioning the endocardial electrodes of a cardiac contractility modulation (CCM) device.

Materials and methods. The CCM system was implanted in 100 patients, of which 60 CCM electrodes were positioned in the most optimal zones of myocardial perfusion, in particular, in the zone of the minor focal-scar/fibrotic lesion (the Summed Rest Score of 0 to 1–2, the intensity of the radiopharmaceutical at least 30%), and in 40 patients according to the standard procedure. Before the implantation of the CCM system, 60 patients underwent tomography (S-SPECT) of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest to determine the most optimal electrode positioning zones and 100 patients underwent transthoracic echocardiography at baseline and after 12 months to assess the effectiveness of surgical treatment.

Results. Improved ventricular electrode positioning technique is associated with the best reverse remodeling of the left ventricular myocardium, especially in patients with ischemic chronic heart failure, with less radiation exposure to the surgeon and the patient, and without electrode-related complications.

Conclusion. At the preoperative stage, it is recommended to perform a synchronized single-photon emission computed tomography of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest before implantation of the CCM device to assess the presence of scar zones/myocardial fibrosis in the anterior and inferior septal regions of the interventricular septum of the left ventricle, followed by implantation of ventricular electrodes in the zone of the minor scar/fibrous lesion, which will allow to achieve optimal stimulation parameters, increase the effectiveness of CCM therapy, reduce the radiation exposure on medical personnel and the patient during surgery.

Terapevticheskii arkhiv. 2024;96(7):675-682
pages 675-682 views

GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register

Krivosheeva E.N., Komarov A.L., Panchenko E.P., Khakimova M.B., Kropacheva E.S., Pogorelova O.A., Balakhonova T.V., Titaeva E.V., Dobrovolsky A.B., Galyautdinov D.M., Vlasova E.E.

Abstract

Aim. To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy.

Materials and methods. The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2–5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay.

Results. Frequency of BARC 2–5 bleedings was 16% (BARC 2 – 46; BARC 3 – 9; BARC 4–5 – 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11–6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41–4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03–3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation.

Conclusion. Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Terapevticheskii arkhiv. 2024;96(7):683-689
pages 683-689 views

Efficacy and safety of levilimab in the treatment of patients with rheumatoid arthritis

Bolotova E.V., Yakovleva E.V., Ilinykh E.K., Rassovskaya Т.A.

Abstract

Aim. Evaluation in real clinical practice of the effectiveness and safety of levilimab therapy in patients with highly and moderately active rheumatoid arthritis (RA).

Materials and methods. A prospective observational study (6 months) involving 35 patients with RA (29 women and 6 men, mean age 53.17±13.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug levilimab (Ilsira).

Results. After 1 month of observation, there was a decrease in the clinical and laboratory activity of the process in the form of a decrease in the number of painful joints – 17.0 (14.0; 20.0) vs 8.0 (6.0; 10.0); p=0.000001, number of swollen joints – 3.0 (2.0; 4.0) vs 0.0 (0.0; 0.0); p=0.000002, reduction in pain intensity according to visual analog scale – 60.0 (60.0; 70.0) mm vs 30.0 (20.0; 40.0) mm (p=0.000001). Also, by the end of the first month of therapy, there was a decrease in clinical activity indices DAS28-ESR by 43%, SDAI by 60%, CDAI by 55%. Positive dynamics of laboratory parameters were noted – a decrease in erythrocyte sedimentation rate by 76%, a decrease in C-reactive protein level by 98%. By the 6th month of therapy, a decrease in RF by 36% and ACCP by 11% was recorded, but the dynamics of these indicators did not reach statistical significance. By the end of 4 weeks of treatment, 24 (68.6%) patients showed an increase in the level of total blood cholesterol – 5.1 (3.91; 6.0) mmol/L vs 6.1 (4.99; 7.07) mmol/L (p=0.000006), while 11 (45.8%) patients from this group had initially elevated cholesterol levels (6.4±0.6 mmol/L). In 5 (14.3%) patients, an increase in alanine aminotransferase (ALT) was recorded in the 4th week – 17.0 (11.0; 25.0) U/L vs 32.0 (22.0; 43.0) U/L (p=0.000062) and aspartate aminotransferase (AST) – 19.0 (14.0; 24.0) U/L vs 25.0 (18.0; 36.0) U/L (p=0.000171), in 1 (2.85%) of the patient, an increase in ALT and AST above normal was noted (ALT 144 U/L, AST 52 U/L), which required discontinuation of levilimab. In 2 (5.7%) patients, by the end of the 4th week a decrease in the absolute number of neutrophils was registered – 3.2 (2.6; 4.0)×10E9/L vs 2.3 (2.0; 2.5)×10E9/L (p=0.002), which did not require discontinuation of treatment, since the number of cells remained more than 1×10E9/L. During treatment with levilimab 162 mg subcutaneously once a week, the proportion of patients taking prednisolone decreased from 46% at the start of therapy to 11% at the end of 6 months of therapy.

Conclusion. Levilimab is a highly effective drug for the treatment of patients with highly and moderately active RA and has a favorable tolerability and safety profile.

Terapevticheskii arkhiv. 2024;96(7):690-694
pages 690-694 views

Clinical notes

Clinical case of generalized amyloidosis (ATTR-amyloidosis) with a progressive course of chronic heart failure. Case report

Golubovskaya D.P., Dren’ E.V., Yurkina A.V., Pecherina T.B., Barbarash O.L.

Abstract

Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.

Terapevticheskii arkhiv. 2024;96(7):695-700
pages 695-700 views

Reviews

4D flow MRI: value and clinical perspectives in patients with pathology of the heart and great vessels (part 2): A review

Yurpolskaya L.A.

Abstract

The study of blood flow is becoming a new trend in cardiology and cardiovascular surgery. Based on the literature and our own data, a review is presented on the use of 4D flow in diseases of the heart and blood vessels. The main state of the question about the features of the application of the technique in various pathologies of the cardiovascular system is described in detail, the priorities, limitations and promising directions of the technique application are considered taking into account the goals of practical medicine. The review consists of two parts. The first is devoted to general issues, limitations of the technique, and issues of 4D flow mapping in patients with lesions of the great vessels. In the second part, the emphasis is on the use of 4D flow MRI in the study of intraventricular blood flow and the application of the technique in congenital heart and vascular diseases.

Terapevticheskii arkhiv. 2024;96(7):701-705
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Dyspnea in post-COVID-19 patients: A review

Podzolkov V.I., Vetluzhskaya M.V., Medvedev I.D., Abramova A.A., Kislenko G.A.

Abstract

New coronavirus infection may lead to long-term consequences, particularly to post-COVID syndrome, one of the most common manifestations of which is dyspnea. Post-COVID-19 shortness of breath may persist from one to several months and even years that results in low quality of life of patients. The review highlights possible risk factors and causes of dyspnea in post-COVID period such as lung damage, cardiovascular pathology, hyperventilation syndrome, dysfunction of the autonomic nervous system, detraining, anemia, etc. The authors present data about COVID-19-associated causes of dyspnea and severity of acute COVID-19. The review emphasizes the importance of a multidisciplinary approach to the diagnosis and treatment of patients with shortness of breath in post-COVID-19 period.

Terapevticheskii arkhiv. 2024;96(7):706-712
pages 706-712 views

History of medicine

The last illness of I.S. Turgenev

Dvoretsky L.I.

Abstract

The article discusses the causes and course of the last illness of I.S. Turgenev. The writer was consulted by many famous French and Russian doctors who made various diagnoses and used various methods of treatment. The primary disease that caused Turgenev's death is myxosarcoma (one of the sarcoma variants), involving soft tissues and thoracic vertebrae. The article presents data and discusses alternative diagnostic versions about the nature of the disease and the causes of death of the great Russian writer.

Terapevticheskii arkhiv. 2024;96(7):713-717
pages 713-717 views


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