The management of acute myocardial infarction in the Russian Federation: protocol for a study of patient pathways

Death rates from cardiovascular disease in Russia are among the highest in the world. In recent years, the Russian government has invested substantially in the healthcare system, with a particular focus on improving access to advanced technology, especially for acute myocardial infarction (AMI). This protocol describes a study to understand the management of AMI in different Russian regions, investigating the role of patient, clinical, and health system characteristic

Chronic thromboembolic pulmonary hypertension after an acute pulmonary embolism: fundamental concepts of diagnosis and review of current treatment options

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and underdiagnosed disorder that leads to right ventricular failure and, subsequently, to death. The article discusses the fundamental concepts of monitoring patients after a pulmonary embolism (PE) in order to timely detect CTEPH. The pathogenetic processes, risk factors and diagnostic criteria of this complication are described. The role of early diagnosis of CTEPH, which may be important in relation to further outcomes, is emphasized. A modern strategy for monitoring patients after PE is presented in detail, where echocardiography plays a key role. The stepwise diagnostic algorithm for CTEPH includes a comprehensive analysis of the patient’s condition: assessment of clinical status, identification of N-terminal pro-brain natriuretic peptide levels, cardiopulmonary exercise testing, imaging diagnostic procedures (ventilation/perfusion lung scanning, pulmonary angiography) and, finally, right heart catheterization. The article provides an overview of modern treatment options. CTEPH is a unique type of pulmonary hypertension because it is potentially curable with surgery — pulmonary thromboendarterectomy. For patients with inoperable or persistent/ recurrent CTEPH, medication therapy is recommended. Currently, the only drug with a high class of evidence for this group of patients is riociguat. A positive effect on exercise tolerance, functional class, and hemodynamic parameters has been shown in the CHEST-1,2 studies. The favorable safety profile of the drug was also demonstrated in the long-term follow-up in routine clinical practice (EXPERT registry). The presence of various options in the management of patients and development of a multimodal therapy makes it possible to provide high-quality care to patients with CTEPH, and, namely, fast and accurate diagnosis plays a key role in timely treatment

Statins and highly sensitive cardiac troponins: cardiotoxicity or cross-reactivity?

To date, hypolipidemic drugs of the statin group are among the most popular therapeutic agents used for the prevention and treatment of the most common worldwide atherosclerotic cardiovascular diseases (CVD). Therefore, considerable attention of researchers is focused on statins to study the additional effects of these drugs, which is accompanied by the discovery of new mechanisms of action and properties that should be taken into account to optimize the tactics of managing patients with CVD. In addition to the key lipid-lowering effect of statins associated with the inhibition of the ratelimiting enzyme (3-hydroxy-3-methylglutaryl-coenzyme A reductase), researchers report a variety of other properties of these drugs. Important circumstances contributing to the disclosure of new effects of statins are: improvement of research methods, and first of all, their sensitivity and specificity; the discovery of new molecules and molecular pathways that may be affected by statins. In general, the currently established numerous non-lipid effects of statin drugs can be divided into two groups: favorable and side effects, which must be taken into account when managing patients with CVD and comorbid diseases. Thanks to recent studies using modern clinical diagnostic cardiomarkers (highly sensitive cardiac troponins (CT)), molecular genetic and morphological methods, potential cardiotoxic properties of statin group drugs have been identified. Of particular concern are the data on a statininduced increase in the concentration of highly sensitive CT, which are a key and generally recognized criterion for myocardial damage. In this article we discuss possible mechanisms of increasing the concentration of CT and cardiotoxic effects when using statins

МикроРНК: роль в патофизиологии фибрилляции предсердий и возможности использования в качестве биомаркера

The aim of the study was to analyze medical literature on the role of microRNA in the pathophysiology of atrial fibrillation and the possibilities of using microRNAs as biomarkers.The analysis of modern medical literature was carried out using the PubMed – NCBI database.Atrial fibrillation (AF) is a common and serious cardiovascular disease. The pathophysiological mechanisms underlying the development of atrial fibrillation are not entirely clear. In addition, there are no optimal biomarkers for early detection and assessment of the prognosis for patients with atrial fibrillation. Recently, the attention of researchers has been directed to the molecules of microRNA. There is a lot of evidence that they are involved in the pathogenesis of neurological, oncological, and cardiovascular diseases. This review examines the role of microRNAs in the pathophysiology of atrial fibrillation. The possibility of using microRNA as a biomarker for the diagnosis and prediction of atrial fibrillation is also discussed.MicroRNAs play a crucial role in the pathophysiology of atrial fibrillation, regulating the mechanisms of atrial remodeling, such as electrical remodeling, structural remodeling, remodeling of the autonomic nervous system, and impaired regulation of calcium levels. The stability of microRNAs and the possibility to study them in various biological fluids and tissues, including blood, make these molecules a promising diagnostic biomarker for various cardiovascular diseases. The presented data clearly indicate that AF is associated with changes in the expression level of various microRNAs, which can be quantified using a polymerase chain reaction. Further research is required to assess the role of microRNAs as biomarkers for atrial fibrillation, in particular to establish precise reference limits.Проведен анализ современной медицинской литературы по базе данных PubMed – NCBI. Фибрилляция предсердий является широко распространенным и серьезным сердечно-сосудистым заболеванием. Патофизиологические механизмы, лежащие в основе развития фибрилляции предсердий, не совсем ясны. Кроме того, отсутствуют оптимальные биомаркеры для раннего выявления и оценки прогноза пациентов с фибрилляцией предсердий.В последнее время внимание исследователей привлекли молекулы микрорибонуклеиновой кислоты (микроРНК). Накоплено немало данных, согласно которым они участвует в патогенезе неврологических, онкологических и сердечно-сосудистых заболеваний. Рассмотрена роль микроРНК в патофизиологии фибрилляции предсердий. Также обсуждается возможность использования микроРНК в качестве биомаркеров для диагностики и прогнозирования фибрилляции предсердий

Cardioprotective Strategies for Doxorubicin-induced Cardiotoxicity: Present and Future

The improvement of drugs and protocols of chemotherapeutic treatment has led to improved outcomes and survival in patients with cancer. But along with this, at first glance a positive point, there was another interdisciplinary problem, which is the need for early detection and treatment of developing cardiotoxicity when taking chemotherapy drugs. The study of cardioprotective strategies has recently become increasingly relevant, due to the fact that many patients who have successfully undergone treatment for cancer have a high risk of developing or are at high risk of death from cardiovascular diseases. One of the main drugs for the treatment of a number of oncological diseases is an anthracycline – type antibiotic-doxorubicin. This review briefly examines the risk factors and pathophysiological mechanisms underlying anthracycline cardiotoxicity. The current possibilities of cardioprotection of anthracycline cardiotoxicity are considered in detail, and some promising targets and drugs for improving cardioprotective strategies are discussed

Comboridity of chronic obstructive pulmonary disease and cardiovascular diseases: general factors, pathophysiological mechanisms and clinical significance

Currently, the comorbidity (combination) of chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) is an important problem for the health care. This is due to the high prevalence and continuing growth of these pathologies. CVD and COPD have common risk factors and mechanisms underlying their development and progression: smoking, inflammation, sedentary lifestyle, aging, oxidative stress, air pollution, and hypoxia. In this review, we summarize the current knowledge related to the prevalence and frequency of cardiovascular diseases in people with COPD and the mechanisms that underly their coexistence. The implications for clinical practice, in particular the main problems of diagnosis and treatment of COPD/CVD comorbidity, are also discussed

Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1)

Аритмогенные эффекты доксорубицина

The article discusses the adverse arrhythmogenic effects of an antitumor drug – doxorubicin.Doxorubicin has a significant effect on the action potentials and ion currents of cardiomyocytes, the dynamics of intracellular calcium concentration.Oncological diseases are the leading causes of death and disability of the population, causing extremely high socio-economic damage. Among the many currently available drugs for the treatment of cancer, an important place is taken by the anthracycline antibiotic – doxorubicin. However, adverse concomitant effects on several organs and systems of the human body, in particular on the cardiovascular system, do not allow the full use of the high potential of doxorubicin`s antitumor effectiveness. Cardiotoxicity of doxorubicin is manifested in the form of electrocardiographic abnormalities and arrhythmias, degenerative cardiomyopathy and chronic heart failure. The authors consider the following arrhythmogenic effects of doxorubicin: the mechanisms of influence of doxorubicin on electrocardiographic parameters, the action potential of cardiomyocytes, cardiac ion currents and the dynamics of intracellular calcium concentration. The study and assessment of specific pathophysiological mechanisms of arrhythmogenic effects of doxorubicin is necessary for the development and justified use of cardioprotective measures.В статье обсуждаются неблагоприятные аритмогенные эффекты противоопухолевого препарата – доксорубицина. Доксорубицин оказывает значимое влияние на потенциал действия и ионные токи кардиомиоцитов, динамику внутриклеточной концентрации кальция.Онкологические заболевания – одна из ведущих причин смертности и инвалидизации населения. Среди множества доступных на сегодняшний день методов лечения онкопатологий важное место занимает антибиотик антрациклинового ряда – доксорубицин. Однако неблагоприятное сопутствующее воздействие на организм человека, в частности сердечно-сосудистую систему, не позволяет в полной мере использовать противоопухолевые свойства доксорубицина. Кардиотоксичность доксорубицина проявляется в виде электрокардиографических нарушений и аритмий, дегенеративной кардиомиопатии, хронической сердечной недостаточности. В обзоре рассмотрены аритмогенные эффекты доксорубицина: влияние на электрокардиографические показатели, потенциал действия кардиомиоцитов, сердечные ионные токи, динамику внутриклеточной концентрации кальция. Изучение и установление конкретных патофизиологических механизмов аритмогенного действия доксорубицина необходимы для разработки и обоснованного применения кардиопротекторных мероприятий

Validation of the SIRENA score for assessing the risk of inhospital mortality in patients with acute pulmonary embolism in an independent sample

Aim. To validate the SIRENA score  in assessing the risk of inhospital mortality in patients with pulmonary embolism (PE) in an independent sample.Material and methods. This retrospective, single-center study was based on the Samara Regional Cardiology Center. The risk of inhospital mortality was assessed using the SIRENA score, which includes such parameters as left ventricular ejection fraction <40%,  immobilization in prior 12 months, creatinine clearance <50 ml/min, syncope, cyanosis on admission. For each positive sign, 1 point is assigned. Low risk is set at score of 0-1, high — ≥2.Results. The study included 452 patients with PE hospitalized from 2004 to 2019, of which 221 (48,9%) were men (mean age, 60,0 years (50,5-70,0)).  With SIRENA score of 0, 1, 2, 3, and 4, inhospital mortality was 4,1%, 10,8%, 18,8%, 40,0%, and 100%, respectively. Mortality at SIRENA low risk (<2) was 7,1%, and at high risk (≥2) — 20,5% (odds ratio (OR), 3,34; 95% confidence interval (CI), 1,74-6,43; p<0,001).  The predictive sensitivity and specificity for inhospital mortality for the SIRENA score were 70,5% and 60,8%, respectively. Area under the ROC-curve for the SIRENA score was 0,71 (95% CI, 0,63-0,79), while for Simplified Pulmonary Embolism Severity Index (sPESI) — 0,69 (95%  CI, 0,60-0,77).  With high risk on both scales (sPESI and SIRENA), inhospital mortality was 24,2% (OR, 4,09, 95% CI, 2,07-8,09; p<0,001).Conclusion. On an independent sample, the SIRENA score  showed  a high predictive ability in predicting adverse outcomes in patients with PE with a sensitivity of 70,5% and a specificity of 60,8% (AUC=0,71, 95% CI, 0,63-0,79), comparable with the sPESI