Vol 51, No 2 (2023)

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Left ventricular diastolic function in adult patients with an atrial septal defect and its age-dependent changes over time after transcatheter closure of the defect

Kovalchuk I.A., Rafaeli I.R., Kryukov V.A., Rogatova A.N., Azarov A.V., Kurnosov S.A., Ioseliani D.G.


Background: There are no echocardiographic (echoCG) criteria to predict whether adult patients with an atrial septal defect (ASD) will develop post-procedural left ventricular (LV) failure after the defect closure.

Aim: To evaluate the LV diastolic function before and after the intervention in ASD patients depending on their age and, based on this, to identify potential echoCG risk factors for the development of acute heart failure immediately after the ASD closure.

Materials and methods: This retrospective study included 69 patients with the mean age of 44.2 ± 14.5 years and 57 (82.6%) being women. The patients were divided into 2 age groups: group 1 included 39 (56.5%) patients aged 18 to 49 years (mean ± SD, 35.4 ± 9.4 years) and group 2, 30 (43.5%) patients aged 50 to 74 years (mean ± SD, 60.1 ± 6.1 years). The characteristics of the ASD, heart chambers and LV diastolic function were assessed with transthoracic and transesophageal echoCG. The indexed indicators of the left atrial (LA) and LV volumes were measured before the intervention and in the postoperative period and compared. LV diastolic function was assessed by the e’ lateral (determined by tissue Doppler imaging, TDI) and E/e’ ratio (reference values > 10 cm/s and < 8, respectively).

Results: The indexed LA volume at baseline in the second group was slightly higher than in the first one (27.6 ± 9.8 ml/m2 and 25.4 ± 7.1 ml/m2; p = 0.311), whereas there was no between-group difference in the baseline indexed LV volume parameters (41.8 ± 7.9 ml/m2 and 42.4 ± 8.6 ml/m2, respectively; p = 0.768). Immediately after the closure of the ASD, LV diastolic function deteriorated. In the patients below 50 years of age, this difference was non-significant, despite significant changes in the E/e’ values (from 7.6 ± 3.6 to 9.9 ± 4.1; p = 0.012). In the second age group, this parameter increased significantly (from 9.2 ± 5.7 to 13.1 ± 4.3, respectively; p = 0.005). The TDI index (e’ lateral) decreased in both groups: in the group 1, from 11.9 ± 2.5 to 9.1 ± 2.2 (p < 0.001) and in the group 2, from 9.3 ± 3.6 to 7.9 ± 1.6 (p = 0.061). Two patients of the elderly group, in whom sings of LV failure were identified immediately after the defect closure, by echoCG showed the lowest TDI values (е’ lateral) (7.8 and 8.0 cm/sec before closure and 6.4 and 7.0 cm/sec thereafter), as well as the highest values E/e’ before closure (13.4 and 13.1, respectively). In the long-term (12.5 ± 6.5 months on average), the E/e’ index decreased in both age groups, compared to that in the early postoperative period, approaching the preoperative parameters (group < 50 years of age: 7.6 ± 3.6 → 9.9 ± 4.1 → 8.7 ± 4.8, group ≥ 50 years of age, 9.2 ± 5.7 → 13.1 ± 4.3 → 10.8 ± 5.6). The TDI e’ indicators also shifted close to their initial values, increasing from 9.1 ± 2.2 to 11.6 ± 1.9 in the group < 50 years of age and from 7.9 ± 1.6 to 8.9 ± 2.8 in the group ≥ 50 years of age. In the long-term, the LA volume index in both groups was unchanged, compared to its baseline values. The indexed LV end diastolic volume and end diastolic diameter increased significantly at one year after the ASD closure in both groups; however, they did not fall outside the reference ranges, and the LV systolic function indicators remained at the same level.

Conclusion: LA volumes and LV function demonstrated the expected positive remodeling after the transcatheter ASD closure. Potential echoCG risk factors for the development of acute heart failure immediately after the ASD closure were identified. These were low baseline rates of early diastolic velocity of the mitral ring (TDI e’ lateral) of less than 8.0 cm/sec and high LV filling pressure (E/e’) of more than 13 in the patients with ASD.

Almanac of Clinical Medicine. 2023;51(2):67-76
pages 67-76 views

Comparison of in-hospital and long-term mortality and assessment of their predictors in patients with myocardial infarction and unstable angina

Shchinova A.M., Potekhina A.V., Dolgusheva Y.A., Efremova Y.E., Osokina A.K., Filatova A.Y., Sorokin E.V., Shestova I.I., Provatorov S.I.


Background: The extent of myocardial damage largely determines both in-hospital and long-term mortality in patients with acute coronary syndrome. According to the literature, the in-hospital and long-term mortality rates in patients with unstable angina (UA) are lower than those in the patients with myocardial infarction (MI).

Aim: To evaluate the in-hospital and long-term mortality rates and their predictors in patients undergoing in-patient treatment for acute coronary syndrome (MI and UA) in the regional cardiovascular center with the service territory of 1 million persons.

Materials and methods: This retrospective registry study enrolled 1130 patients (715 [63.3%] men, 415 [36.7%] women) who were treated for UA and MI in the regional cardiovascular center in 2019. Based on the discharge diagnosis, the patients were divided into two groups: patients with MI (n = 766) and those with an UA episode (n = 364). The in-hospital and delayed mortality rates, as well as their predictors, were analyzed in both groups. The mean duration of the follow-up was 17.8 ± 3.6 months.

Results: The in-hospital mortality in patients with confirmed MI was 11.1% (85 patients) versus 0.27% (1 patient) in the UA patients (p < 0.001). The independent predictors of in-hospital mortality in MI patients were a decreased left ventricular ejection fraction (LV EF) (odds ratio (OR) 0.9021, 95% confidence interval (CI) 0.8209–0.9914, p = 0.0324), chronic kidney disease C3a and above (OR 9.3205, 95% CI 2.6706–32.5283, p = 0.0005), and the extension of coronary involvement at coronary angiography (OR 1.3526, 95% CI 1.0667–0.0127, p = 0.0127). The long-term mortality in MI patients was 10.4% (72 patients) with no significant difference from that in UA patients (9.9%, 36 patients, p = 0.76). The independent predictors of long-term mortality after MI were older age (OR 1.12, 95% CI 1.01–1.22, p = 0.0052), chronic kidney disease C3a and above (OR 2.3375, 95% CI 1.1392–4.7963, p = 0.0206), decreased EF (OR 0.8895, 95% CI 0.73–0.99, p = 0.0364), atrial fibrillation on admission (OR 3.1462, 95% CI 1.3510–7.3268, p = 0.0079), and diabetes mellitus (OR 2.3163, 95% CI 1.2552–4.2744, p = 0.0072). In the UA patients, the predictors of the long-term mortality were a decrease in LV EF (OR 0.9139, 95% CI 0.8683–0.9619, p = 0.0006) and in blood hemoglobin level (OR 0.9729, 95% CI 0.9544–0.9917, p = 0.0050).

Conclusion: The in-hospital mortality in UA patients is lower than that in MI patients, with comparable long-term mortality. This indicates the need of active follow-up of the patients with past UA, irrespective of the endovascular assessment and intervention.

Almanac of Clinical Medicine. 2023;51(2):77-85
pages 77-85 views

Efficacy and safety of molnupiravir in adult outpatients with COVID-19

Pshenichnaya N.Y., Omarova K.G., Balykova L.A., Zaslavskaya K.Y., Zemskov D.N., Taganov A.V., Belyy P.A., Gorelov A.V., Pushkar D.Y.


Background: One of the basic principles for the treatment of COVID-19 patients is the early initiation of etiotropic therapy. The evidence base for assessment of the efficacy and safety of antivirals for COVID-19 continues to expand with new clinical trials. One of the promising etiotropic medications is molnupiravir.

Aim: To evaluate the efficacy and safety of molnupiravir (Esperavir®) in outpatients with COVID-19.

Materials and methods: This randomized comparative open-label clinical study was conducted from December 1, 2021 to March 11, 2022 in 12 research centers in the Russian Federation. The study involved 240 outpatients with mild and moderate COVID-19. The mean age of patients was 43.5 years; 70,0% (168/240) of the patients had comorbidities, mainly obesity grade ≥ II and arterial hypertension. The outpatients were treated with molnupiravir (Esperavir®, “PROMOMED RUS” LLC, Russia) in 4 capsules 200 mg twice daily (every 12 hours), with the single dose being 800 mg and the daily dose 1600 mg. Duration of treatment was 5 days. The patients were followed up for 28 days. The patients in the standard treatment group (n = 120) received antiviral therapy recommended for outpatients by the provisional guidelines effective at the time of the study. Pathogenetic and symptomatic therapy in both groups was comparable.

Results: The results of the clinical study in 240 outpatients with mild or moderate COVID-19 showed that molnupiravir at a dose of 800 mg twice daily for 5 days significantly reduced (by 4-hold at days 14–15 of the follow-up) the risk of disease progression to more severe course, compared with the standard therapy group (2.5% (3/120) and 10.0% (12/120) of patients; p = 0.0149.) By days 6–7 of the follow-up, the virus had been eliminated in 71.67% of the patients treated with the study drug and only in 58.3% (70/120) of the patients in the standard therapy group. Complete clinical recovery at days 6–7 was achieved in 19.2% (23/120) of the patients in the molnupiravir group, compared to 5.8% (7/120) in the standard therapy group. Compared to the standard therapy, treatment with molnupiravir also significantly reduced the frequency and severity of the disease symptoms, such as cough and change in odor or taste perception over the last 24 hours, already at 6–7 days after the start of treatment. Molnupiravir treatment was well tolerated, most adverse events were mild. There were no cases of drug withdrawal or dose modification of the study drug due to adverse events.

Conclusion: The results of the clinical study of antiviral agent molnupiravir (Esperavir®) have proven its benefits over standard therapy in outpatients with mild and moderate COVID-19 in terms of the disease worsening risk reduction and hospitalization, the rate of viral elimination, the changes in symptoms severity over time, improvement of the patients’ general status and clinical condition and reduction of COVID-19 complications both in patients without and with risk factors for severe COVID-19 outcomes. The results of this study demonstrated a favorable safety profile of molnupiravir in COVID-19 patients.

Almanac of Clinical Medicine. 2023;51(2):86-98
pages 86-98 views


Sudden cardiac death in myocarditis

Taradin G.G., Ignatenko G.A., Kugler T.E.


According to statistics, myocarditis is one of the leading causes of sudden cardiac death (SCD) in children and young adults. The etiology of myocarditis includes infectious and non-infectious, including autoimmune diseases, as well as toxicities and hypersensitivity to various drugs or bites of insects, spiders, snakes, etc. The risk of myocarditis among patients with COVID-19 is 15.7-fold higher than that in the general population. The most common cause of death in myocarditis is heart arrhythmia, such as ventricular tachyarrhythmia, ventricular fibrillation, or severe bradycardia. Genetic predisposition, ion and metabolic disorders, mechanisms of autoimmune response, and direct cardiotoxic action in viral diseases play a role in the pathophysiology of inflammatory myocardial damage. While the majority of patients with myocarditis, who died suddenly, was asymptomatic or had few symptoms, a timely and accurate diagnosis of myocarditis seems to be an important challenge for prevention or minimization of SCD risk. Nonetheless, at present there is no convincing evidence of an association between laboratory and instrumental parameters and the SCD risk in such patients. Endomyocardial biopsy remains the "golden standard" in the diagnosis of myocarditis. Biomarkers (troponins or creatine phosphokinase) are not highly specific. The most common electrocardiographic findings in myocarditis are sinus tachycardia and nonspecific changes in the ST-T segment. The presence of Q wave, bundle branch block, Brugada syndrome, shortened or prolonged QT interval, and early ventricular repolarization are associated with an increased risk of SCD in myocarditis. Given the absence of specific echocardiographic signs of myocarditis, special attention is paid to the assessment of the size of the cardiac chambers, wall thicknesses, global and regional systolic and diastolic function of both the left and right ventricles, visualization of pericardial effusion and intracardiac thrombi. A combined cardiac magnetic resonance imaging using T2-weighted imaging and early and late gadolinium enhancement provides high diagnostic accuracy and seems to be a useful tool in the stratification of patients with suspected acute myocarditis. With the established etiology of myocarditis, specific therapy is necessary to eliminate the pathogen. It is necessary to take into account the likely arrhythmogenic effects of the drugs used in treatment. Non-steroidal anti-inflammatory drugs are generally not indicated in patients with myocarditis because they cause renal impairment and sodium retention, which can exacerbate left ventricular dysfunction and increase the risk of SCD. In the case of severe conduction disturbances and ventricular tachyarrhythmias, implantation of a pacemaker or cardioverter-defibrillator is necessary.

Almanac of Clinical Medicine. 2023;51(2):99-109
pages 99-109 views

Cognitive impairment and its treatment in patients with multiple sclerosis

Zabirova A.K., Bakulin I.S., Poydasheva A.G., Zakharova M.N., Suponeva N.A.


Cognitive impairment (CI) is a relatively common manifestation of multiple sclerosis (MS), which can occur with any type of the disease course and activity. The largest CI prevalence and severity are observed in progressive MS. In relapsing-remitting MS the most prominent deterioration of cognitive functions is seen during relapses; however, in some patients it can continue also throughout remission. In a small number of patients CI can be the most significant symptom of the disease; in addition, it sometimes can be the only clinical feature of the relapse. Despite this, in clinical practice CI remains out of the focus of attention, and is not evaluated when assessing the disease severity and/or activity, while CI is not included into EDSS. Nonetheless, a number of specialized neuropsychological tests and batteries has been developed recently, which can be used for both screening and detailed assessment of CI in MS, as well as for assessment of its changes over time.

CI has a negative impact on MS patients' quality of life, their social interactions, daily and occupational activities. The influence of disease-modifying agents on CI has been poorly investigated; however, there is evidence that they can reduce the degree of CI. The optimal choice of pathogenetic treatment in patients with CI remains understudied. There is no convincing evidence of the effectiveness of symptomatic pharmacological treatment of CI in MS, and cognitive rehabilitation is the only approach with confirmed effectiveness. Considering the limitations of this technique (its availability, quite a big number of sessions), there is a need to search for other methods to increase its efficacy, including non-invasive neuromodulation (in particular, transcranial direct current stimulation or transcranial magnetic stimulation). This article is focused on a brief review of the main diagnostic methods of CI in MS, its pathogenetic and symptomatic treatment, and cognitive rehabilitation techniques, as well as on the results of the studies on non-invasive neuromodulation.

Almanac of Clinical Medicine. 2023;51(2):110-125
pages 110-125 views


Hemorrhage into a somatotropinoma аs a first reason for examination of a patient with previously undiagnosed acromegaly and papillary thyroid cancer

Nurullina G.M., Pushkarev I.N., Pigarova E.A., Latkina N.V., Akhmadullina G.I.


Pituitary apoplexy is a rare acute condition that can be caused by hemorrhage into the pituitary adenoma or its infarction. This is accompanied by severe headache, nausea, vomiting, photophobia, visual and oculomotor disorders, loss of consciousness, and can also lead to a decrease in the production of a number of hormones by the pituitary gland, i.e. hypopituitarism. We present a clinical case of a 42-year female patient with previously undiagnosed acromegaly and papillary thyroid cancer. The reason for the examination was clinical symptoms of pituitary apoplexy. Right hemithyroidectomy with central and lateral lymphadenectomy was performed for her papillary thyroid cancer, followed by radioactive iodine therapy due to an increased risk of cancer progression. Hemorrhage into the pituitary adenoma in this patient has led to panhypopituitarism and remission of acromegaly. Insulin-like growth factor 1 and growth hormone levels during oral glucose tolerance test were within the reference values, which made the diagnosis of acromegaly challenging.

Almanac of Clinical Medicine. 2023;51(2):126-133
pages 126-133 views

Identification of Reed-Berezovsky-Sternberg cells in lymphatic nodes in classic Hodgkin's lymphoma by flow cytometry: a clinical case series

Abbasbeyli F.М., Fedenko A.A., Zeynalova P.A., Mushkarina Т.Y., Melnikova A.A., Grivtsova L.Y.


Despite their B cell origin, Reed-Berezovsky-Sternberg tumor cells (RBS) in classic Hodgkin's lymphoma (cHL) demonstrate an absolutely unique phenotype. Immunohistochemistry of RBS cells is positive for CD15 antigen in most of cases, CD30, PAX-5; they do not express the T cell antigen CD3, В cell CD19, and in most cases are negative for the B cell antigen CD20, as well as for common leukocyte antigen CD45. Taking into account such unequivocal immunophenotype, RBS cells can be identified by multiparameter flow cytometry. Thus, J.R. Fromm et al. (2006, 2014) have convincingly shown the possibility to identify RBS cells in a puncture and/or biopsy sample of lymphatic nodes in cHL and were of the fair opinion that such rather simple and reproducible technique as flow cytometry could be an additional diagnostic instrument in cHL.

We have tested the technique proposed by J.R. Fromm et al. for the assessment of lymphatic node involvement in cHL and used 8 to 10-parameter flow cytometry for detection RBS cells in cHL in 8 biopsy samples of a lymphatic node, and confirmed the feasibility to identify RBS cells by high performance flow cytometry. We also performed morphological and immunohistochemical assessment of the biopsy samples of lymphatic nodes from patients with suspected cHL. The study included clinical cases with immunohistochemically confirmed cHL (n = 8), and the control samples were from those with other diagnoses than Hodgkin's lymphoma. In all cases of cHL we found RBS cells. In future we plan to analyze larger case samples by flow cytometry.

Almanac of Clinical Medicine. 2023;51(2):134-142
pages 134-142 views

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