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Rational Pharmacotherapy in Cardiology

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Vol 20, No 1 (2024)
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ORIGINAL STUDIES

4-12 1038
Abstract

Aim. To evaluate the usage of antihypertensive drugs (AHDs) and their combinations in participants aged 35 to74 years with arterial hypertension (AH) in the population-based study ESSE-RF3.

Material and methods. Representative samples of the population aged 35 to 74 years from 15 regions of Russia (n=28731) with a response rate over 70% were examined in the ESSE-RF3 study. Therapy received by 9944 participants with AH (with systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg, or when the subject was taking AHDs) was analyzed. Information about AHDs intake (brand name of the drug) was recorded by questionnaire and coded according to International Nonproprietary Names by classes. Statistical analysis was performed using the open-source R 4.1 environment. Comparison of discrete indicators between groups was performed using Fisher’s exact test. The significance level for all tested hypotheses was taken as.05. The study was approved by the Ethics Committee of FGBI “NMRC TPM” of the Ministry of Health of the Russian Federation, each participant signed an informed consent.

Results. Among the patients receiving therapy for AH, angiotensin-converting enzyme inhibitors (ACEIs) were used by 38.8% of participants, angiotensin receptor blockers (ARBs) — 31.6%, betablockers (BBs) — 29.0%, сalcium channel blockers (CCBs) — 21.5%, diuretics — 18.6%, 1.1% — outdated AHDs; 8.6% — other groups of drugs. Monotherapy was used by 53.1% of patients, 33.1% of participants received two, and 13.9% received three AHDs. Among participants taking two or more AHDs (including single-pill combinations (SPC)), males most often received the combination of BB+ ACEI and females — BB+ARBs. SPC AHDs were used by 10.3% of those receiving therapy (males: 9.8%, females: 10.6%). Among SPCs, the top three combinations were CCBs + ACEIs (28%), diuretics + ACEIs (27.5%), and diuretics + ARBs (24.4%).

Conclusion. The population study ESSE-RF3, based on the survey of a representative sample of the Russian population aged 35-74 years, showed that more than a half of participants with AH receiving therapy were used the monotherapy, only every tenth of those treated received SPC. The problem of insufficient patients’ literacy was indicated — about 1% of patients received outdated AGPs. In addition, 8.6% of patients used non-AHDs for the treatment of AH. For improving the control of AH treatment, it is necessary to increase the adherence of patients to the prescribed therapy and more strict adherence of doctors to the published guidelines for AH treatment.

13-18 322
Abstract

Aim. Assessment of the correlation between cardiac remodeling, functional status and electrical remodeling after cardiac resynchronisation therapy (CRT) in patients with non-ischaemic cardiomyopathy.

Material and methods. A single center, prospective, observational study included 50 patients with non-ischaemic cardiomyopathy who were candidate for CRT implantation. All patients prior to CRT and then 3 months after implantation had standard 12-lead surface ECGs to assess QRSd for assessment electrical response, for assessment of left ventricular ejection fraction (LVEF) and volumes (left ventricular end diastolic and systolic volume, LVEDV and LVESV), mitral regurgitation (degree of mitral regurgitation), pulmonary artery systolic pressure (for diagnosis of pulmonary hypertension), NYHA class and 6 minute walk test (6MWT) to assess patient’s functional capacity.

Results. 50 patients with CRT were included (35 males and 15 females, mean age 54.88±7.48 years). All patients were in sinus rhythm with QRS duration (QRSd) ≥120 ms, EF<35% and left bundle branch block. After 3 months; there was significant improvement in QRSd in 82% of the cases (145.3±16.3 ms vs 133.3±17.2 ms, p<0.001). NYHA class improved at least one class in 78% and 6 min walk test improved in 80% (168.5 [131.0; 181.0] m vs 280.0 [237.0; 297.0] m, p<0.001). LVEF increased significantly in 74% of study cases (28.6±2.7 vs 34.5±3.1, p value 0.001) also there were statistically significant improvement in LVEDV (267.0±45.7 to 221.8±41.9 ml, p=0.002) and LVESV (137.43±47.19 to 105.03±42.7 ml, p=0.003). There was statistically significant correlation between QRSd and NYHA class (r=0.392, p=0.005), QRSd and 6MWT (r=0.323, p=0.022) and QRSd with LVEF (r=0.672 with p<0.001). Only seven patients showed improvement in the 3 parameters: LVESV, QRS duration and 6 min walk test.

Conclusion. The CRT-pacemaker implantation was associated with significant improvement in QRSd, NYHA class, 6MWT and LV volumes in the short-term period. QRSd improvement was significantly correlated with functional status and LV EF.

19-26 680
Abstract

Aim. The aim of our study was to investigate the influence of polymorphic markers of CYP3A4*22 CYP3A4*22 (c.522-191C>T, rs35599367), CYP3A5*3 (c.219237A>G, rs776746), ABCB1 rs1045642 (c.3435T>C) and rs4148738 (c.2692-2236C>T) genes on the plasma concentration of apixaban, on changes in prothrombin time (PT), activated partial thromboplastin time (APTT), and bleeding development in patients taking apixaban.

Material and methods. The study included 108 patients with non-valvular atrial fibrillation and deep vein thrombosis receiving apixaban in therapeutic doses. Genotyping was performed by real-time polymerase chain reaction. Apixaban concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode. Because the daily dose of apixaban was different (5, 10, and 20 mg daily), the residual equilibrium concentration (Cmin,ss) of apixaban was adjusted relative to the daily drug dose (Cmin,ss/D). PT and APTT were determined using an automatic coagulometer analyzer Destiny Max (Tcoag, Ireland). Statistical processing was performed in SPSS Statistics 20.0 program.

Results. We found that patients with CT ABCB1 (rs4148738) C>T genotype had higher Cmin,ss /D value than patients with TT genotype (6.23 [4;13] vs 5.77 [4;17], p=0.018). No statistically significant associations were found between carriage of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T gene polymorphisms and Cmin,ss /D value of apixaban. Also, there was no significant effect of carrying polymorphisms rs35599367, rs776746, rs4148738,rs4148642, and the above genes on the risks of hemorrhagic complications. However, the influence of ABCB1 (rs1045642) C>T polymorphism on the PT value was found (TT ABCB1 (rs1045642) C>T genotype carriers the CT value wassignificantly higher than in CT genotype (17.0 [40;112] vs. 14.9 [35;132]) p=0.044).

Conclusion. It was found that the Cmin,ss /D value was higher in patients with CT ABCB1 (rs4148738) C>T genotype than in patients with TT genotype. At the same time, carriage of polymorphisms of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T genes did not affect the pharmacokinetics of apixaban and the risk of bleeding. We also identified the effect of ABCB1 (rs1045642) C>T gene polymorphism on the PT value.

NOTES FROM PRACTICE

27-34 685
Abstract

Aim. To determine the incidence of the no-reflow phenomenon in patients with acute coronary syndrome (ACS) undergoing primary percutaneous coronary intervention (PCI), and to study factors associated with its occurrence in the daily work of the City Clinical Hospital.

Material and methods. Of the 2090 patients with ACS admitted to N. I. Pirogov City Clinical Hospital No.1 in the period from 01.01.2017 to 01.11.2022 there were 2 groups of patients with PCI: group 1 (n=59) included patients with initial antegrade coronary blood flow TIMI 0 and final blood flow TIMI 0-2 (with the no/ slow-reflow phenomenon); Group 2 (n=149) included patients with initial coronary blood flow TIMI 0 and final antegrade coronary blood flow TIMI 3 (without the no/slow-reflow phenomenon).

Results. The no-/slow-reflow phenomenon was observed in 2.8% of cases. Patients with no-/slow-reflow phenomenon more frequently had diabetes mellitus (42.4% vs. 22.8%, p=0.003), a history of stroke (12.1% vs. 3.4%, p=0.016), higher Killip class and "pain-to-balloon" time 7 [3; 16] vs. 4 [2.3; 8.25] hours, p=0.004. Binary logistic regression identified "pain-to-balloon" time as the most significant predictor of no-/slow-reflow phenomenon development [Odds Ratio (OR)=1.03; 95% CI: 0.95-0.996; p=0.02] and the proximal level of occlusion in infarct-related coronary artery. The incidence of in-hospital mortality was 6.1 times higher in the no-/slow-reflow group compared to the normal blood flow group [OR=6.102±0.433; 95% CI: 2.614-14.247; p<0.05].

Conclusion. The development of the no-/slow-reflow phenomenon was observed in 2.8% of patients in clinical practice N. I. Pirogov City Clinical Hospital No.1. Its development was associated with an increase in the incidence of unfavorable outcome of the disease in the hospital. The total time of myocardial ischemia, the presence of diabetes mellitus, a history of stroke, and a higher Killip class of acute heart failure at admission were more often associated with the development of the no-/slow-reflow phenomenon. The proximal level of damage to the infarct-related artery and "pain-to-balloon" time were independent predictors of the no-/slowreflow phenomenon.

35-45 460
Abstract

Aim. To study the effect of various therapy regimens with enhanced external counterpulsation (EECP) on exercise tolerance, quality of life, indices of structural and functional state of cardiovascular system in patients with stable coronary artery disease (CAD) complicated by chronic heart failure (CHF).

Material and methods. The study included patients with stable CAD complicated by CHF with reduced and intermediate left ventricular ejection fraction (LVEF) from the randomized EXCEL trial (NCT05913778; n=120) and additionally patients with similar inclusion and exclusion criteria (n=90) who were randomized into groups with different EECP treatment regimens for 12 months: Group 1 (n=40): course of 35 hour-long procedures; Group 2 (n=40): course of 35 hourlong procedures every 6 months; Group 3 (n=30): course of 20 hour-long procedures then constantly 1 hour per week; Group 4 (n=30): constantly 2 hours per week; Group 5 (n=30): course of 20 hour-long procedures then constantly 2 hours per week; Group 0 (placebo ; n=40): course of 35 hour-long procedures with compression pressure 80 mm Hg. All patients at baseline and after 12 months were assessed for clinical status, quality of life (MLHFQ, SF-36), NT-proBNP levels, LVEF, as well as exercise tolerance (6-minute walk test; 6MWT) initially, after 3, 6, 9 and 12 months. Correlation analysis and risk assessment of adverse events (combined endpoint — combination of cases of adverse cardiovascular events, deaths, hospitalizations for CHF, new-onset of atrial fibrillation, diabetes, decreased renal function) was performed.

Results. Treatment effectiveness had positive correlation with EECP duration (r(S)=0,670; p<0,001) and treatment regimen (r(S)=0,620; p<0,001). The maximum effect (changes in NT-proBNP levels, LVEF, clinical status, quality of life) was noted in the combined and constant regimen groups (5, 4, 2). The increase of 6WMTdistance was 6,6% in group 0, 24,9% in group 1, 44,5% in group 2, 31,8% in group 3, 49,1% in group 4, 58,6% in group 5. The proportion of patients with an increase in 6WMT-distance >20% after 12 months was 7,7%, 72,5%, 97,5%, 76,7%, 90%, 100%, respectively. Cumulative event-free survival was highest in groups 5, 4, and 2 (0,97, 0,93, and 0,86, respectively), and the risk of developing combined endpoint in these groups was minimal (0,035, 0,075, and 0,150, respectively).

Conclusion. The effect of EECP treatment in patients with coronary artery disease complicated by CHF depended on the EECP hours and regimen. Alternative EECP regimens (with more treatments spread evenly over the year) in addition to optimal medical therapy may improve the management of these patients.

 

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

46-51 445
Abstract

Aim. To study the features of the course of primary and recurrent myocardial infarction and compare their prognosis in the acute stage of the disease within the framework of the hospital register of the vascular center.

Material and methods. The data from the acute coronary syndrome register of N. V. Sklifosovsky Research Institute for Emergency Medicine were used. The inclusion criteria were: transmural acute myocardial infarction (AMI) with ST-segment elevation (codes I21.0-I21.3 according to the International Classification of Diseases); permanent residence in Moscow and the Moscow region. The described part of the study included all patients with transmural myocardial infarction (codes I21.0-I.21.3) admitted from January 1, 2017 to December 31, 2017. Of the AMI patients admitted during this period (n=329), 214 met the inclusion criteria, with primary AMI in 153 and recurrent AMI in 61.

Results. Patients with recurrent AMI were significantly older, more often had a disability group. Smoking and arterial hypertension were more frequent risk factors among patients with recurrent AMI than in primary AMI. All indices reflecting the severity of coronary artery disease and its complications were also significantly more common in the group with recurrent AMI. Diabetes mellitus was more common in these patients. Taking medications before hospitalization, as well as the regularity of this intake, were significantly more common in patients who had repeated AMI. The mortality rate of patients with recurrent AMI was 4.6 times higher than that of patients with primary AMI. Such complications as atrial fibrillation and flutter, intracardiac conduction disturbance requiring temporary endocardial stimulator placement, acute heart failure requiring intra-aortic balloon counterpulsation, respiratory failure requiring artificial ventilation, cardiogenic shock were significantly more common in patients with recurrent AMI. Kaplan-Meyer curves clearly demonstrate the differences in hospital mortality among the two groups of patients. These curves also clearly show that patients with primary AMI died mostly in the first days of the disease, but patients with recurrent AMI could die at a much later date, up to 12 days after admission. Analysis of factors determining the mortality risk during hospitalization showed that recurrent AMI is an independent predictor of death.

Conclusion. The results of our work indicate the need for prompt identification of patients who had previously undergone AMI upon their admission to the vascular center, as well as the development of more active prevention tactics for such patients.

CLINICAL CASE

52-56 386
Abstract

Pulmonary artery sarcoma (PAS) is a malignant and very rare tumor with frequent misdiagnosis. A rare clinical case with this pathology is presented. The patient had daily fever for 6 months, he was examined in various hospitals, but the cause of fever could not be determined. In our hospital, echocardiography revealed a mass in the left pulmonary artery (PA) with obstruction. CT-angiopulmonography showed a filling defect in the left PA, blocking the lumen of the artery by 90%. According to histopathology, the patient was diagnosed with pulmonary artery sarcoma. Subsequently, the following was performed: thrombendarterectomy from the pulmonary artery, combined pneumonectomy on the left side, suturing of the secondary atrial septal defect, followed by 3 courses of monochemotherapy with paclitaxel. After 1 year and 9 months, due to disease progression the patient died. The prognosis of PAS depends on early diagnosis, so doctors should be aware of this disease and use the best treatment options.

57-62 440
Abstract

The article describes a clinical case of biventricular arrhythmogenic cardiomyopathy (ACM) presented with myocardial infarction (MI) — like event in a young patient. The patient was hospitalized with suspected acute coronary syndrome and an episode of ventricular tachycardia (VT). Based on increased cardiac troponin, left ventricular systolic dysfunction with wall motion abnormalities, and nonobstructive coronary arteries the initial diagnosis of type 2 MI was made. To verify the etiology behind VT and ventricular structural abnormalities cardiac magnetic resonance imaging (MRI) was performed. Abnormalities of both right and left ventricles demonstrated by MRI and supported by the genetic testing established the diagnosis of biventricular ACM. Since the diagnosis was made, initially diagnosed MI was reassessed in favor of acute myocardial injury as a characteristic of ACM course. ACM should be included into differential diagnosis with MI and acute myocarditis in patients with elevated troponin and nonobstructive coronary arteries.

POINT OF VIEW

63-68 490
Abstract

Heart failure with reduced ejection fraction (HFrEF) is a public health issue, because some patients, despite using standard treatment, still develop worsening heart failure. The risk of adverse outcomes is especially high in patients who require readmission or emergency care on an outpatient basis. They need a new type of treatment. Vericiguat is the first oral soluble guanylate cyclase stimulator approved for the treatment of adults with symptomatic HFrEF. This article summarizes the main results of the use of this drug. The effectiveness and tolerability of vericiguat, the dependence of its action on the initial state of patients (the presence of coronary heart disease, atrial fibrillation, renal failure, the level of N-terminal pro b-type natriuretic peptide (NT-proBNP) and the duration of the period after hospitalization) are considered. It is reported that the use of the drug reduces the risk of hospitalization for worsening HF and death from cardiovascular diseases in all patients with HFrEF, regardless of the considered baseline parameters, but does not significantly affect the patients’ quality of life of. These results may be useful in determining the place of vericiguat in the management of a growing population of patients with chronic HFrEF who have experienced recent deterioration despite receiving standard therapy.

69-76 488
Abstract

About 300 million non-cardiac operations are performed annually worldwide. In developed countries, an increasing number of such operations are performed in older patients with comorbid cardiac pathology. The leading cause of perioperative mortality is cardiovascular complications. The national and international guidelines published in the last year on cardiovascular assessment and correction of the risk of cardiac complications during non-cardiac operations contain several contradictory provisions. First of all, this refers to the methods of preoperative risk assessment: which is better — to base on scales, functional status assessment or biomarkers (BNP/ NT-pro-BNP) determination? Questions remain about the most appropriate algorithm for preoperative evaluation of patients with suspected cardiac pathology (the need for preoperative non-invasive tests or limited to biomarkers evaluation), some of these algorithms have been validated in recent studies. Several publications address the problem of drug therapy in non-cardiac surgery, both previously studied drugs (statins, beta-blockers) and new ones (colchicine, nicorandil). Perioperative myocardial injury syndrome and its possible drug prevention continue to be studied. This review considers recent publications on this topic, which have not yet been reflected in the guidelines and may influence their correction in the future. The article also discusses the problems of implementing existing guidelines in clinical practice. The publications of the last year presented in the review help researchers and practitioners to form their views on existing controversial issues. Ultimately, this will promote the use of an individualized approach in the management of this category of patients.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

77-84 476
Abstract

Infections associated with cardiac implantable electronic devices (CIED) pose a serious risk to the patient’s health due to the high mortality rate of this type of complications. This literature review presents risk factors, microbiology and pathogenesis, as well as the rationale and evidence for the use of antibiotic-releasing envelopes in patients with an increased risk of infectious complications. As a preventive measure, envelopes for implantable cardiac devices with antimicrobial impregnation are used, which have been developed to reliably hold devices in place, provide a stable environment and reduce the risk of infectious complications. Since it is believed that most infections occur during cardiac devices implantation, these covers have become an effective method of prevention. New technologies of the envelopes promise to reduce the CIED pocket infection rate. Preclinical and clinical data confirm the effectiveness of local antibiotic delivery through synthetic shells or ICS shells based on intracellular matrix, eluting rifampicin/minocycline and gentamicin, respectively. Moreover, the shell of the extracellular matrix usually stimulates tissue remodeling and angiogenesis, thereby minimizing inflammation and promoting bacterial clearance. Given the continued growth in the implantation of cardiac devices and the associated infectious complications, innovative approaches to infection prevention during the implantation of arrhythmological devices are crucial.

85-102 471
Abstract

Infective endocarditis (IE) is a rare disease with a potentially high mortality rate. The patient "portrait" is changing, there is an increase in the proportion of elderly people with concomitant diseases and degenerative defects, prosthetic valves and minimally invasive cardiac operations, implanted intracardiac devices, and hemodialysis. An additional significant negative contribution is made by the transformation of the etiological picture — an increase in the species diversity of pathogens, a decrease in the proportion of streptococci, a steady increase in the staphylococcal and enterococcal etiology of IE. The IE treatment success depends on the competent administration of antibacterial therapy. Clinicians are guided by two main documents: the national clinical guidelines "Infective endocarditis and infection of intracardiac devices" of 2021 and the European clinical guidelines "ESC Guidelines for the management of endocarditis" of 2023. The article summarizes updated data on the optimal prescription of antibacterial therapy, presented in a convenient and understandable format for the practicing physicians. Schemes for prescribing intravenous antibiotic therapy in a hospital are presented not only for traditional pathogens (Staphylococcus sp., Streptococcus sp. and Enterococcus sp.), but also for rare pathogens that cause significant difficulties (pathogens of the HACEK and non-HACEK group, Coxiella burnetii, Bartonella sp., Brucella sp., Tropheryma whipplei, Mycobacterium sp., fungi). Separately, the principles of empirical antibacterial therapy with the most effective treatment regimens not only for left-sided IE, but also for different variants of right-sided IE are presented in detail. New modern possibilities of outpatient oral antibiotic therapy for IE are presented. In conclusion, prospects for the development of conservative IE treatment are proposed.

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ISSN 2225-3653 (Online)