Vol 21, No 1 (2019)


The new 2018 European guidelines for the management of arterial hypertension: the most important aspects of use in real-life clinical practice

Ostroumova O.D., Kochetkov A.I.


Aim. To present the fundamental standpoints of renewed 2018 European guidelines for the management of arterial hypertension and to discuss aspects of its use in real-life clinical practice with due consideration of Russian experts opinions. Materials and methods. 2018 European guidelines for the management of arterial hypertension and Russian Society of Cardiology Memorandum on these guidelines are discussed. Results and conclusion. Fundamental standpoints of 2018 European guidelines for the management of arterial hypertension as well as essential and important in context of real-life clinical practice changes in comparison with the previous revision are presented. Much attention is given to risk factors and associated with hypertension organ damage detection. Special focus is made on the main principle of blood pressure pharmacological control - “one pill strategy”. A step to step regimen for prescription of combined antihypertensive therapy where renin angiotensin aldosterone system (RAAS) inhibitors are first line medications is presented. At the first stage the choice combination includes angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker and dihydropyridine calcium channel blocker or diuretic. It is outlined that for the first time in the guidelines the use of 3-component antihypertensive therapy in the form of “one pill” is emphasized and its actual components are specified (RAAS inhibitor, calcium channel blocker and diuretic). Also a small subset of patients in whom it is possible to use antihypertensive medications in monotherapy is described. The management of elderly and very elderly patients and patients with senile asthenia syndrome is described. Target blood pressure levels depending on comorbid disorders existence such as diabetes mellitus, chronic kidney disease, ischemic kidney disease, stroke and/or transient ischemic attack as well as patient age are discussed. All standpoints of European guidelines for the management of arterial hypertension are discussed from the point of view of Russian experts that is presented in Russian Society of Cardiology Memorandum. The second part of the article presents possibilities of one pill strategy use in combined antihypertensive therapy based of valsartan and discusses the importance of patients’ compliance to blood pressure pharmacological control and ways of improving this compliance.
Consilium Medicum. 2019;21(1):9-16
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The possibility of the blood pressure control at the outpatient stage

Larina V.N., Fedorova E.V., Sidorova V.P., Kladovikova O.V.


Background. The control of blood pressure (BP) is given great attention due to the increase in its incidence in recent years and the established connection of the uncontrolled course of hypertension with the risk of developing serious cardiovascular complications and death. Aim. To present up-to-date data on various aspects of blood pressure control at the outpatient stage. Materials and methods. To write this review, a search was conducted for domestic and foreign publications in Russian and international bibliographic databases (PubMed, eLIBRARY, Medscape, etc.) for the last 0.5-10 years. The review included articles from peer-reviewed literature. Results. Covers issues of treatment adherence and the factors affecting it. Attention is paid to the issues of patient education, the basics of independent control of blood pressure, including through various mobile applications, which are considered as necessary factors that improve blood pressure control and treatment adherence. Conclusion. Based on the available results of numerous studies, it is not always possible to control the level of blood pressure in everyday clinical practice. Possible approaches to improving this situation are the assessment of treatment adherence and the active involvement of patients in antihypertensive treatment with constant independent control of blood pressure.
Consilium Medicum. 2019;21(1):19-24
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Sartans in hypertension treatment: advantages of candesartan use

Leonova M.V.


Aim. To present a scientific review of angiotensin II (AT II) receptor blockers (sartans) clinical pharmacology, in particular pharmacologic and clinical characteristics of candesartan. Materials and methods. A literature search for Russian and foreign publications since year 1999 was conducted in Russian and international databases (PubMed, eLibrary and others) in order to write this review. Results. In the last years AT II receptor blockers or sartans have been widely used for arterial hypertension treatment. Despite general characteristics of this antihypertensive medications group such as mechanism of action, possibility of administration one time a day, good tolerance, and minimal adverse effects, there are clinical and pharmacological differences between medications that determine their effectiveness. It is shown that candesartan kinetics of interaction with AT receptors is specific, that results in more expressed hypotensive effect and high trough/peak index of hypotensive effect. Candesartan pharmacokinetics and hypotensive effect do not depend on CYP2C9 metabolizing ferment genetic polymorphism. According to several metaanalyses results candesartan has advantages in level of blood pressure (BP) decrease that results in BP-dependent advantages. In a large observational study candesartan showed better results of influence on arterial hypertension cardiovascular outcomes in comparison with losartan, that demonstrates possible BP-independent clinical and pharmacological advantages. At present sartan therapy is becoming more affordable because of generics development. Hyposart (manufacturer - pharmaceutical company Polpharma, Poland) has an acknowledged place among candesartan generics. It has shown complete equivalence to original medication in bioequivalence studies, what is important in evidence-based medicine. Conclusion. Candesartan is one of the most powerful medications of AT II receptor blockers group that is proved by its clinical and pharmacological characteristics. Advantages of its hypotensive effect and long-term effectiveness were demonstrated in several studies and metaanalyses and are associated with BP-dependent and BP-independent effects determined by receptor interaction characteristics.
Consilium Medicum. 2019;21(1):25-30
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Age aspects of acute myocardial infarction

Khorolets E.V., Shlyk S.V., Bychkova O.I.


Aim. To study the clinical and laboratory features of patients with acute myocardial infarction with ST segment elevation (STEMI) depending on age. Materials and methods. Included 150 people diagnosed with STEMI in the first day of the disease. Clinical, laboratory features of patients were studied. In the dynamics of inpatient treatment, with hospitalization (visit 1) and discharge (visit 2), indicators of the N-terminal prostatic natriuretic peptide (NTproBNP) and growth differentiation factor 15 (GFD-15) were evaluated. Results. The average age of patients with STEMI was 61.7±2.9 years. The age-related clinical and laboratory features of the course of STEMI are described. With comparable hemodynamic data, markers of myocardial necrosis in patients with STEMI with age, a statistically significant increase in the level of NTproBNP and GFD-15 was detected. An increase in GDF-15 levels in patients over 60 years old >1200 ng/ml identifies a high risk of recurrent myocardial infarction. In the dynamics of inpatient treatment of patients with STEMI up to 75 years, a decrease in laboratory parameters NTproBNP and GFD-15 was revealed. The NTproBNP indicator has a positive correlation with the functional class of chronic heart failure (r=0.20, p<0.04), the GRACE scale (r=0.38, p<0.001), reflecting the unfavorable prognosis of patients with STEMI. Conclusions. At the hospital stage of treatment of patients with STEMI at the hospital stage of treatment, there was a decrease in the level of NTproBNP and GFD-15 in patients under 75 years of age, an increase in these indicators in patients over 75 years of age, which determines the most unfavorable prognosis.
Consilium Medicum. 2019;21(1):31-35
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Fatal cardio-vascular events risk stratification in ischemic heart disease patients with implantable cardioverter-defibrillators: role of noninvasive electrophysiological predictors

Melnik N.V., Tsaregorodtsev D.A., Ilych I.L., Khamnagadaev I.A., Sulimov V.A.


Aim. To study possibilities of non-invasive electrophysiological methods (microvolt Т-wave alternance - mTWA) heart rate turbulence (HRT), deceleration capacity (DC) use in stratifying risk of arrhythmic events and mortality in patients with ischemic heart disease (IHD) and implantable cardioverter-defibrillator (ICD). Materials and methods. The study included 45 patients with verified IHD diagnosis and indications for ICD implantation. In all patients serum creatinine level, glomerular filtration rate (GFR), and serum lipid fractions were determined and 24-hour Holter electrocardiogram (ECG) monitoring was performed where HRT, mTWA, and DC as well as acceleration capacity (AC), and heart rate variability (HRV) were determined. Survived patients were followed-up for no less than 30 months (mean follow-up 48 [42; 51] months, maximum - 70 months). The study endpoints were death from any cause and “arrhythmic” endpoint (appropriate ICD discharge or sudden cardiac death - SCD). Results. Ten (22.2%) patients died from different causes during follow-up period. Arrhythmic endpoint (appropriate ICD therapy or SCD) was observed in 13 (28.9%) cases. Significant differences in DC, CRT, and serum creatinine level were observed in patients who survived and died. No patients with normal CRT or in low-risk group died during follow-up. There were significant differences in number of ventricular extrasystoles (VES) morphologies according to 24-hour Holter ECG monitoring and in serum cholesterol level in patients with or without arrhythmic events. Multifactor regression analysis showed serum creatinine level to be an independent risk factor of lethal outcome, and both polytope VES and serum cholesterol level were shown to be independent predictors of arrhythmic endpoint. Conclusion. Non-invasive electrophysiological markers have demonstrated high negative significance in lethal outcome prognosis in patients with IHD and ICD. Serum creatinine level was shown to be the only independent lethal outcome predictor. Polytope VES and serum cholesterol level were demonstrated to be independent predictors of arrhythmic endpoint.
Consilium Medicum. 2019;21(1):36-45
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Chronic heart failure in the practice of the therapist: is it difficult to recognize it?

Kirichenko A.A., Ebseeva E.Y.


Background. Congestive heart failure (CHF) diagnosis can present a problem as many of its symptoms are non-specific and have limited diagnostic value. Aim. To present modern approaches to CHF diagnosis and an algorithm of actions for therapist on examination of a patient with complaints of dyspnoe and/or leg swelling. Materials and methods. Literature search of Russian and foreign publications in Russian and international search systems (PubMed, eLIBRARY and other) was performed for articles published in the last 15 years. Results. If the patient has symptoms and signs suspicious for CHF it is reasonable to evaluate natriuretic peptides level. Level of NT-proBNP<125 pg/ml is considered normal, and cardiac dysfunction is likely to be excluded. Another disorder should be searched for. Level of NT-proBNP>125 pg/ml is associated with high probability of CHF; these patients should be referred to echocardiography. If CHF diagnosis is confirmed, its etiology should be defined. Conclusion. NT-proBNP is an important analysis that in addition to clinical data allows improving diagnostics of heart failure in primary assessment.
Consilium Medicum. 2019;21(1):46-49
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Antagonists of mineralocorticoid receptors in the treatment of patients with post-infarced heart failure: the role of eplerenon

Kashtalap V.V., Sedykh D.Y., Barbarash O.L.


Aim. To present modern view on the role of mineralocorticoid receptor antagonists (MRA), eplerenone in particular, in treatment of patients with post-infarction cardiac failure, and to analyze its effectiveness and safety. Materials and methods. Data fr om scientific sources published in Russia and abroad in 1984-2018 years were analyzed. Conclusion. Acute myocardial infarction with congestive cardiac failure (CCF) development is associated with sympathoadrenal system and renin-angiotensin-aldosterone cascade hyperactivation that results in pathologic myocardium remodeling following fibrosis. Within the concept of quality of life improvement and lifetime increase in patients after myocardial infarction it is important to prescribe MRA, eplerenone in particular, besides renin-angiotensin-aldosterone system inhibitors and b-adrenoblockers (b-AB). Accumulated data on MRA effectiveness in patients with CCF including patients after myocardial infarction is the basis for inclusion of these medications in National guidelines on CSF diagnostics and treatment of Russian Society of Cardiology and Russian Scientific Medical Society of Therapists. According to these guidelines medications of this group are recommended (level IA) to the use (combined with angiotensin-converting enzyme inhibitors - ACE inhibitors and b-AB) in all patients with medium severe and severe CHF who have decreased contractile function of left ventricle in order to decrease mortality risk and readmission frequency and to improve symptoms. A similar point of view is presented in European Society of Cardiology guidelines wh ere MRA also have IA level of evidence to the use as a first line medication (together with ACE inhibitors and b-AB for CHF treatment). The presented clinical case supported by the evidence of previously conducted studies demonstrates the leading role of eplerenon in therapy that results in prognosis improvement in patients with CHF after myocardial infarction who have low left ventricular ejection fraction.
Consilium Medicum. 2019;21(1):51-55
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Combined therapy with proton pump inhibitors and clopidogrel - focus on cardiovascular risk

Kochetkov A.I., Ostroumova O.D., Kravchenko E.V., Bondarets O.V., Guseva T.F.


Aim. To analyze accessible studies on the problem of potential interaction of proton pump inhibitors and clopidogrel and to evaluate the influence of combined therapy with these pharmacologic agents on cardiovascular adverse effects development. Materials and methods. Data from 43 foreign and Russian literature sources including international clinical guidelines, randomized and prospective clinical studies, cohort and retrospective studies, clinical registries, metaanalyses and systematic reviews were analyzed. Results. The issue of proton pump inhibitors and P2Y12 thrombocytes receptors inhibitor clopidogrel interaction is discussed in the context of cardiovascular risk and influence on essential adverse cardiovascular events (including acute coronary syndrome, stent thrombosis, necessity of myocardial revascularization, stroke, myocardial infarction, all-cause and/or cardiovascular mortality, symptomatic or non- symptomatic gastrointestinal hemorrhage) in patients taking dual antiplatelet therapy. Standpoints of current international guidelines concerning possibility and necessity of theses medicines use in combination are presented. Data from a significant amount of studies on proton pump inhibitors influence on clopidogrel clinical effectiveness are discussed. The results of analyzed studies demonstrate increased risk of adverse cardiovascular events in the group of patients with ischemic heart disease who receive concomitant treatment with proton pump inhibitors. In particular, in several metaanalyses it was demonstrated that concurrent administration of acetosalicylic acid, clopidogrel, and proton pump inhibitors reduces frequency of gastrointestinal hemorrhage, but at the same time increases risk of major adverse cardiovascular events, increases probability of stent thrombosis and necessity of revascularization. Nevertheless, these results were not confirmed in multiple randomized clinical studies. Conclusion. Considering available literature data we can make a conclusion of necessity of large well-orchestrated randomized clinical studies conduction in order to find a conclusive answer on safety of proton pump inhibitors use in patients after percutaneous coronary intervention or coronary artery bypass surgery, including patients after acute coronary syndrome.
Consilium Medicum. 2019;21(1):56-66
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Potassium and magnesium deficiency, its role in cardiovascular disease development and possibilities of correction

Baryshnikova G.A., Chorbinskaya S.A., Stepanova I.I., Blokhina O.E.


Aim. To evaluate the significance of potassium and magnesium in human health formation and their role in development of functional disorders of cardiovascular and nervous system and in development and progression of cardiovascular diseases. Materials and methods. Data from 55 literature sources published in Russia and abroad in the period of 1972-2018 years are reviewed. Results. Potassium has an important role in cells bioelectrical activity organization, cell action potentials formation and neuromuscular excitability and conductibility sustentation. Hypokalemia symptoms can be quite various. Frequent ones include neuromuscular conductibility disorders, various changes in cardiovascular system (myocardial contractile function decrease, blood pressure (BP) decrease, cardiac cavities dilatation). Potassium intake increase is followed by lower incidence of cardiovascular and cerebrovascular events, new cases of diabetes mellitus (DM) type 2, left ventricular hypertrophy, cardiac insufficiency, and arrhythmias. Magnesium is a universal regulator of biochemical and physiological processes in the body, a cofactor of more than 300 enzymes participating in biochemical reactions, and a natural physiologic potassium antagonist. It reduces potassium release from sarcoplasmic reticulum and protects cells from potassium overload in conditions of ischemia. Therefore magnesium reduces systemic and pulmonary vascular resistance that results in systemic BP reduction and moderate cardiac index increase. Also reliable evidence indicating moderate but clinically significant antihypertensive effect of magnesium medications was received. Magnesium deficiency is associated with increase of total cholesterol level, low-density lipoprotein, and triglycerides. Serum magnesium level is inversely proportional to the degree of cardiovascular disorders development risk, particularly of cardiac rhythm disorders and IHD complications. European Food Safety Authority (EFSA) confirmed that patients’ health status improved after a period of magnesium adequate intake. Even severe hypokalemia and hypomagnesemia often remain non-diagnosed in clinical practice. Medical practitioner of any kind should remember of potassium and magnesium deficiency clinical manifestations in order to manage it or prevent its development in patients with risk factors by adequate treatment assignment. Described potassium and magnesium interrelations as well as relatively high frequency and severity of combined deficit of these macronutrients justify advisability of the use of combined medications containing К+ and Mg2+in treatment of many disorders. An additional effect is observed when these electrolytes levels are corrected together. Conclusion. Control of electrolyte balance, first of all, of potassium and magnesium balance, should be an intrinsic part of present day clinical practice. In patients with high risk of hypokalemia and hypomagnesemia development either its correction in case of detection or prevention of potassium and magnesium deficiency development should be performed. Potassium and magnesium balance maintenance provides additional therapeutic effect in patients with AH, DM, congestive heart failure, IHD (including myocardial infarction), as well as in patients with high risk of stroke or severe ventricular arrhythmia development.
Consilium Medicum. 2019;21(1):67-73
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Diabetes mellitus and cardiovascular diseases. An updated approach to lifestyle modification and treatment of patients with diabetes mellitus type 2

Volkova E.A., Malygina O.F.


Background. The issue of optimal antihyperglycemic therapy choice presents essential, taking into consideration the increase of number of patients with diabetes mellitus (DM) type 2 and excessive mortality of these patients from cardiovascular diseases (CVD). The updated recommendations presented in consensus report of American Diabetes Association (ADA) in cooperation with European Association for the Study of Diabetes (EASD) in 2018 reflect complex approach to treatment of adult patients with DM type 2 that aims not only to improve glycemic control, but also to decrease CVD incidence and mortality. Materials and methods. In order to write this review we analyzed ADA/EASD consensus report of 2018 as well as Russian algorithms and recommendations on DM treatment and several foreign sources including 2008 documents from US Food and Drug Administration (FDA) and the documents from American Association of Clinical Endocrinologists (AACE) published over the past year. Results. A complex control of risk factors that includes patient’s lifestyle change and use of safe and effective medications that will contribute to lipid metabolism, arterial blood pressure and thrombocyte function normalization is required in order to reduce CVD risk and mortality in patients with DM type 2. Lifestyle modification is placed special focus on. It comprises patients’ encouragement and competence increase as well as development and implementation of an individualized program of nutrition intervention and patients’ physical activity increase. In patients with DM type 2 glycemia self-control is considered to be of great importance because it allows the trained patients to control the disease course much better. A favorable prognosis is possible only when complex individual approach is used. Conclusion. Despite development of new effective and safe medications, more than ½ of the patients do not reach glycemia target levels. Therapeutic inactivity, that is multifactorial, is of great significance. In order to cope with it efforts are required both from the whole health care system and from medical practitioners and patients themselves. Modern combined antihyperglycemic therapy that has effect on various pathogenic mechanisms and allows to level down glycemia variability and increase treatment compliance is quite actual. During all stages of DM type 2 treatment it is essential to bear in mind that multifactor and individualized approach is required in order to achieve long-term results.
Consilium Medicum. 2019;21(1):74-80
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Comparison of antiarrhythmic medications propafenone and amiodarone injection forms effectiveness in medicamentous cardioversion of paroxysmal atrial fibrillation

Tarasov A.V., Kosykh S.A., Bushueva E.V., Davtyan K.V., Miller O.N.


Background. According to present 2016-2017 recommendations, propafenone and amiodarone are the main antiarrhythmic medications (AAM) for medicamentous sinus rhythm (SR) restoration. Direct effectiveness and safety comparison of these medications injectable forms for atrial fibrillation (AF) paroxysm treatment on pre-hospital stage is one of the pressing issues. Aim. To compare effectiveness and safety of propafenone and amiodarone use in urgent SR restoration in patients with paroxysmal AF on pre-hospital stage. Materials and methods. An open randomized multicenter prospective study PROMETEI-INSK was conducted. The study included 388 patients with AF paroxysm with mean lasting time of 195 minutes. For the purpose of AF paroxysm treatment amiodarone intravenous bolus was used, in group 2 (268 patients) - propafenone intravenous bolus. The compared groups were matched by sex, age, electrocardiogram (ECG) parameters, and anamnesis of arrhythmic events, comorbid pathology, and therapy. The following investigations were performed: physical examination, medical history taking, ECG before and after rhythm restoration, as well as basic vital factors evaluation (such as heartbeat rate, blood pressure). Study results were processed with the use of statistical data analysis software package Statistica 10 for Windows (StatSoft Inc., USA). Results. AAM effectiveness was evaluated for 24 hours until SR restoration. In the group 1 (amiodarone use) the effectiveness was 61.7% (n=74), in group 2 (propafenone) - 77.6% (n=208); p<0.05. The mean time of rhythm restoration in group 1 was 110 minutes, in group 2 - 22 minutes (p<0.05). Relief of AF paroxysm happened in less than 60 minutes in 25.83% (n=31) of patients in group 1, and in 64.5% (n=173) in group 2; p<0.05. There were no significant differences observed in proarrhythmic and other adverse effects. Conclusion. Propafenone in injectable form is an effective and safe AAM in AF paroxysmal form treatment in comparison with amiodarone on pre-hospital stage. In patients with AF who have no changes in cardiac structure amiodarone is not a first line drug for emergency management of recently emerged AF.
Consilium Medicum. 2019;21(1):81-86
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The study of bioequivalence of twо ezetimib drugs after single oral administration in healthy volunteers

Tolkacheva V.V., Malaya I.P., Bagmanova N.K., Kobalava Z.D.


Aim. To compare pharmacokinetics and bioavailability of ezetimib drugs - Otrio, 10 mg tablets (AKRIKhIN, Russia) and Esetrol®, 10 mg tablets (Schering-Plow Labo N.V., Belgium) after single dose under fasting conditions in healthy volunteers. The study was conducted in accordance with the standards of Good Clinical Practice and the legislation of the Russian Federation. Materials and methods. 64 healthy volunteers were enrolled in an open, randomized, crossover study. After overnight fasting drugs (tested and reference drug) were administered as a single dose, separated by two-weeks washout period. Blood sampling for the deterioration of ezetimibe was performed over 72 hours post dose. A validated HPLC-MS/MS method was used for quantification of ezetimibe in plasma. Pharmacokinetic parameters were determined. Results. The 90% confidence intervals of the ratio for the Ln-transformed AUC0-72 and Сmax ratios are within 80-125% according to existing guidelines. Conclusion. Otrio, 10 mg tablets (Akrikhin, Russia) is bioequivalent to Ezetrol®, 10 mg tablets (Schering-Plough Labo N.V., Belgium).
Consilium Medicum. 2019;21(1):87-91
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Captopril in cardiological patients treatment: is there still place for the “first of the Mohicans”?

Valikulova F.Y., Koroleva L.Y., Melnichenko O.V., Duryndina E.M., Muradova F.N., Alekseeva M.M.


Aim. To demonstrate significance and relevancy of the first angiotensin-converting enzyme inhibitor (ACE inhibitor) captopril use in treatment of patients with cardiovascular disorders. Materials and methods. The article covers the issues of captopril use launch, results of the main randomized clinical studies of it, basic pharmacokinetic characteristics, and indications for captopril use from the perspective of the present clinical guidelines. Conclusion. The first oral ACE inhibitor captopril that was developed more than 40 years ago still holds a valuable place in treatment of cardiovascular diseases such as arterial hypertension, myocardial infarction, congestive heart failure and diabetes mellitus complications. Despite development of ACE inhibitors with longer duration of action and new properties, captopril still remains one of the most effective medications with a wide range of clinical use - from uncomplicated hypertensive crises arrest to long-term use in patients with arterial hypertension, diabetes mellitus, and congestive heart failure. Captopril remains one of the few ACE inhibitors that have changed approaches to treatment of patients with heart failure and improved the survival rate of patients after acute myocardial infarction.
Consilium Medicum. 2019;21(1):92-96
pages 92-96 views
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Management of a patient with dyspnea on an outpatient admission

Vertkin A.L., Topolyansky A.V., Knorring G.Y., Shamuilova M.M.


Background. Management of patients with dyspnea syndrome remains complicated in terms of diagnostics and treatment in outpatient conditions. Aim. To present a summary of contemporary view of diagnostic search directions, differential diagnosis in dyspnea syndrome as well as of the main points of therapeutic approach with the focus on diuretics use. Materials and methods. We systematized materials from Russian and foreign publications (PubMed, eLIBRARY and other) for the past 2-15 years as well as present clinical recommendations and guidelines, and provided citations and beliefs of Russian medicine classics about the discussed phenomena in order to write this review. Results. The diagnostic approach in dyspnea syndrome is based in analysis of anamnestic, objective, laboratory and instrumental data and requires from the medical practitioner a scrupulous analytic approach to identify the cause of the disorder and to manage it prescribing pathogenic therapy on time. Diuretics use remains one of the basic approaches to pathogenic therapy. Conclusion. Management of a patient with dyspnea in outpatient conditions remains challenging. It is an interdisciplinary issue that is not completely worked out in terms of diagnostics and treatment and requires fundamental knowledge and awareness of modern approaches to diagnostics and treatment of major disorders characterized with dyspnea syndrome.
Consilium Medicum. 2019;21(1):98-104
pages 98-104 views

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