Expermental research of the effects of benofilin on the functional renal function in the evalution of ethylene glycol toxic loss

Effect of benofilin – a new compound among a new derivative of theophylline and hofitol (70 mg/kg) on functional renal function was studied based on the rat experimental model of acute kidney damage by ethylene glycol. The toxic products of the metabolism of ethylene glycol cause renal tubular damage resulting in acute renal failure (ARF). As a result of the application of benofilin its ability is established to prevent the death of animals in the first day of the experiment. By the ability to prevent impaired kidney function in rats benofilin exceeds the effect of the hofitol

Potentiometric Determination of Ketoprofen at a New PVC Electrode Modified with Ionic Associate of Kristal Violet

Розроблений кетопрофен-селективний електрод із пластифікованою полівінілхлоридною мембраною, що містить як електродоактивну речовину (ЕАР) іонний асоціат (ІА) кетопрофену (КТ) з кристалічним фіолетовим (КФ). Інтервал лінійності електродної функції розробленого електроду міститься в межах 1×10-5–1×10-2 моль/л кетопрофену, межа виявлення становить 5×10-2 моль/л, крутизна 35,0–56,0 мВ/pC. Робочий інтервал рН елек- трода 7–11. A ketoprofenselective electrode with the plasticized polyvinylchloride membrane has been designed. The electrode contains an ionic associate of ketoprofen with a Kristal Violet and responds to ketoprofen in a linear range of 1×10-5–1×10-2 mol/l with a slope of 35–56 mV/pC. These electrod responds with sensitivity at pH 7–11

Experimental research of nephroprotective activity benophylline in myoglobinurical acute kidney injury in rats

Matviychuk O. P., Matviychuk A. V., Gladchenko O. M., Taran A. V. Experimental research of nephroprotective activity benophylline in myoglobinurical acute kidney injury in rats. Journal of Education, Health and Sport. 2017;7(4):774-786. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.583153 http://ojs.ukw.edu.pl/index.php/johs/article/view/4477 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 1223 (26.01.2017). 1223 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2017; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 12.04.2017. Revised: 10.04.2017. Accepted: 25.04.2017. EXPERIMENTAL RESEARCH OF NEPHROPROTECTIVE ACTIVITY BENOPHYLLINE IN MYOGLOBINURICAL ACUTE KIDNEY INJURY IN RATS O. P. Matviychuk, A. V. Matviychuk, O. M. Gladchenko, A. V. Taran National University of Pharmacy, Kharkiv, Ukraine Аbstract The results in this article demonstrate of the dosage of the nephroprotective activity of the newly 7,8-substituted of theophylline are shown: 7-n-methylbenzyl-8-n-bromobenzylidenhydrazinotheophylline (code name benofillin). Nephroprotective activity was supplemented by of acute renal failure, which was called one-time intramuscularly introduced to the thigh 50% water solution of glycerol. Blowing a benofillin on the function of kidneys in rats were given to the minds of the water load. Evaluation of excretory function of kidneys held for the showers of diuresis, glomerular filtration rate, creatinine concentrations, relative reabsorption of water, excretion of potassium and calcium ions, protein content in the urine and it excretion, filtration charge and reabsorption of sodium ions. The result of the dosage was shown that when therapeutic and preventive application of benofillin the quantity of diuresis increased on 1/9 times in comparison with the pathologies. Under the action of benofillin a decrease in the level of urea in blood serum in 1/5 times. The level of creatinin in blood serum slightly increased (1.1 times compared with pathology). The level of contents of urea and creatinine in urine increased in 2.3 and 2.2 times respectively, excretion of these substances by the kidneys has grown 4.6 times that 5 times respectively, which indicates about improvement of the excretory function of the kidneys. The analysis of changes in biochemical indicators in blood and urine in rats demonstrate, hat in the treatment-and-prophylactic use of benofillin the basic parameters of the visible function of kidneys are normalized. On the background of the treatment-and-prophylactic use of benofillin glomerular filtration rate and tubular reabsorption were increased in 4.7 and 1.1 times respectively compared with pathology. The level of sodium in blood serum not changes respectively with control pathology and intact control. The level of sodium in urine decreased in 2.4 times compared with control pathology. Filtration charge and relative reabsorption increased in 7 times each of one decreased in control pathology, relative reabsorption increased in 1.2 times, sodium excretion was has not changed. When applying benofillin the level of protein in the urine was identical to the control. The conducted studies showed the presence of nephroprotektive activity in benofillin, what is expressed in decreasing of proteinuria, excretion of sodium in the urine and retention hyperaemia, increased glomerular filtration rate and diuresis, normalization of acid-forming function of the kidneys. Key words: acute renal failure, nephroprotective activity, diuresis, urea, creatinine, proteinuria, benofillin

EXPERIMENTAL RESEARCH OF DIURETIC PROPERTIES OF NEW 7-METHYL-N-BENZYL-8- SUBSTITUTED THEOPHYLLINE

EXPERIMENTAL RESEARCH DIURETIC PROPERTIES OF NEW 7-METHYL-N-BENZYL-8-SUBSTITUTED THEOPHYLLINE.Matviychuk O.P., Gladchenko O.M., Matviychuk A.V., Ivanchenko D.G.National University of PharmacyZaporozhye State Medical UniversityIntroduction.  Diuretics are widely used in the treatment of a number of diseases caused by a variety of diseases, in which the need to use these drugs. In many cases there is a clinical need to increase urine output for excretion of fluid, reducing its content in tissues and serous cavities. Especially great role of diuretic drugs in the treatment of patients with chronic congestive heart failure. Thanks to properties diuretics cause increased excretion of sodium and water from the body is given a real opportunity to actively influence the fluid and electrolyte disturbances in these patients.The use of diuretic agents (hydrochlorothiazide, furosemide, etacrynic acid, etc.) are often accompanied by side effects, which primarily relate to fluid and electrolyte homeostasis, acid-base balance, carbohydrate metabolism, phosphate, creatinine and uric acid.The search for new medicines that improve the functional activity of the kidneys, is one of the urgent problems of modern experimental pharmacology. Synthesis of modified analogs of biologically active substances of natural origin is a priority for research to address this issue.Given this, it was interesting to conduct forecasting of possible types of pharmacological activity of derivatives 7,8-disubstituted theophylline using the «PASS» (Predectum of Activity Spectra for Substances: Complex & Training), whose work is based on an analysis of dependencies "structure - activity".The results of the computer forecast derivative 7-p-metylbenzyl-8-substituted theophylline showed a high likelihood of these types of compounds of pharmacological activity, diuretical, spasmolytical, psycho-stimulant, analgesic, anti-inflammatory.Investigation methods. To solve the tasks as object of study was first taken 20 compounds synthesized derivatives of 7-n-metylbenzyl-8-substituted theophylline. The influence of new derivatives of p-20 metylbenzyl-8-substituted theophylline on renal function was performed on white male rats weighing 140-190 g Ye.B.Berhina method [1; 5].  Animals in the experiment were in individual metabolic cages adapted to collect urine. Number of animals in the group amounted to 5. Investigated derivatives intragastric administered at a dose of 1/100 of LD50. After 30 minutes, the rats were injected with tap water at the rate of 3 ml per100 g body weight. Urine recorded 2 hours to 4 hours. As a comparison drug used hydrochlorothiazide (hypothiazid) production «Sanofi Aventis»,France.Results and discussion.  Study diuretic activity 7-p-metylbenzyl-8-substituted theophylline showed that these compounds affect renal function. Most of the studied derivatives showed diuretic activity, which used to range from 23.2% to 153.7%. Marked diuretic effect compound found 14 - 7 p-metylbenzyl-8-p-bromobenzylidenhidrazynoteofilin which stimulates excretory renal function in rats and increases urine 4 hours of observation at 153.7% (p <0.01).Thus, our experimental studies demonstrate the effectiveness of computer prediction. The results forecast for the derivatives of 7-n-metylbenzyl-8-substituted theophylline, envisaged a high probability vasodilatation (peripheral) and diuretic activities that were specifically synthesized to produce the intended biological activity that was confirmed by our experiments.Conclusions. Investigated derivatives of 7-n-metylbenzyl-8-substituted theophylline affect renal excretory function that confirms your computer forecast. The most severe action has diuretic compound 14 - 7- p-metylbenzyl-8-p-bromobenzylidenhydrasinotheophylline which revealed a strong diuretic activity that exceeds the effect hypothiazid 2 times. Among the studied compound found 14 derivatives with diuretic activity high, which makes it promising for further in-depth study of specific diuretic activity as a potential diuretic drug.References1. Berhyn, E. B. Methods Study novyh action of chemical compounds on kidney function // Chemical. Pharm. Zh. - 1977. - T. 11, № 5.- P. 3 - 11.2. Brukhanov, V. M., Zverev, J. F.  Side effects of modern diuretics. - Novosibirsk, 2000. -242 p.3. Glaser, G. A. Diuretics. Guidelines for doctors. - M .: Interbuk Business, 1993. - 352 p.4. James A. Sheiman. Pathophysiology of the kidney. Trans. with Eng. 2nd ed., Rev. - M. - SPb .: "Publisher Binom" - "Nevsky Dialect", 1999. - 206 p.5. Preclinical studies of medicines. / Ed. O.V. Stefanova. - K .: Publishing house "Avicenna", 2001. - 528 p.6. Lapach, S. N.  Statistic Methods in Medical and Biology with Research Using EXCEL / S. N. Lapach, A.V. Chubenko, P.N. Babich - K .: Morion, 2000. - 320 p.7. Mashkovskiy,  M. D.  Medicines / M. D.  Mashkovskiy. - [15th ed., Rev., Corr. and add.]. - M .: RIA "Novaya Volna", 2008. - 1206 p.8. Natochin, V. Clinical and molecular physiology of osmoregulation renal function (the 200th anniversary of the birth F.G.YA. Henle) / Y. Natochin // Clinical Nephrology. - 2009. - № 4. - S. 25-31.9. Alexandrov, K. V. Synthesis of i-junction of two physical hіmіchnі vlastivostі vodorozchinnih pohіdnih 3 benzilksantinu / K. V. Aleksandrov, S. V.  Levіch, O. S.  Skoda, D. M. Yurchenko // Current issues of pharmaceutical and medical science and practice - (2015), №1 (17) c. 60-65.10. Pruglo, Ye. S.  Diuretic activity of 3- (5-bromfuran-2-yl) -4-R- (4H) -1,2,4-triazoles-5-thiones, their derivatives and S-2- (5-bromfuran-2- yl) -5-Rґ-thiazolo [3,2-b] [1,2,4] triazoles-6 (5H) -ones / Ye. S. Pruglo, A. S. Gotsulya, O. I. Panasenko, Ye. G. Knysh.  // Topical issues of pharmaceutical and medical science and practice. - 2015. - № 3 (19). - S. 9-13.11. Ivanchenko, D. G. Synthesis, physicochemical and biological properties of 1,8-disubstituted theobromine. IV. 8 thioderivatives-R-1-n-metylbenzylteobrominu / D. G. Ivanchenko // Topical issues of pharmaceutical and medical science and practice. - 2015. - № 3 (19). - P. 4-8.12. Lysyuk, R. M.  Analysis of the range and modern herbal medicines for the treatment of urinary tract / R. M.  Lysyuk,  R. Darmohray, N. I. Gudz, T. Kalyniuk // Technology of medicines and organization of pharmaceutical business. - Coll. Science. works co. NMAPE named P. L. Shupyk - 24 (4) / 2015 c. 264-269.13. Thomas, D.  Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy  / Thomas D. Barbour , Guang Sheng Ling, Marieta M. Ruseva  at all //  Kidney International (2016) р. 1-9.14. Wayne, Lam.  Is Routine Postoperative Diuresis Renography Indicated in All Adult Patients After Pyeloplasty for Ureteropelvic Junction Obstruction  /  Wayne Lam, Archana Fernando, Rami Issa  at all. //  Urology, Volume 85, Issue 1, January 2015, Pages 246-251.15. Caffeine and diuresis during rest and exercise: A meta-analysis. / Yang Zhang , Aitor Coca , Douglas J. Casa at all. //  Journal of Science and Medicine in Sport - Volume 18, Issue 5, September 2015, Pages 569–574.16. Sunal Makadia, MD. The Diuresis Clinic: A New Paradigm for the Treatment of Mild Decompensated Heart Failure / Sunal Makadia, MD,,Tanya Simmons, RN, BSN, CHFN, Sharon Augustine, CRNP at all. //  The American Journal of Medicine - Volume 128, Issue 5, May 2015, Pages 527–531.17. Kushal, Kumar. Terminalia arjuna bark extract improves diuresis and attenuates acute hypobaric hypoxia induced cerebral vascular leakage / Kushal Kumar, Sarika Sharma, Vivek Vashishtha at all. // Journal of Ethnopharmacology - Volume 180, 2 March 2016, Pages 43–53.18. Chen,  Y .  Basic research ASSA14-03-08 Gastrin and D1 Dopamine Receptor Interact to Induce Natriuresis and Diuresis / Y Chen, LD Asico, S Zheng, at all. // Heart 2015;101:A11 doi:10.1136/heartjnl-2014-307109.27.19. Boscolo, P.  Renal toxicity and arterial hypertension in rats chronically exposed to vanadate /  Paolo Boscolo, Marco Carmignani, Anna Rita Volpe, at all. // Heart 2015;101:A11 doi:10.1136/heartjnl-2014-307109.27.20. Incidence of acute kidney injury in critically burned patients resuscitated with crystalloid and colloid according to parameters of transpulmonary thermodilution, diuresis and lactic acid / P Extremera Navas, M Sanchez Sanchez, I Pozuelo Echegaray, at all. //  Crit Care. 2015; 19(Suppl 1): P358.21. Alexander, JJ.  CD11b is protective in complement-mediated immune complex glomerulonephritis.  / Alexander JJ, Chaves LD, Chang A, et all. // Kidney Int. 2015;87:930–939.22. Wang, T.D. 9c.04: Treatment with lcz696 compared to at1-receptor blockade is associated with non-sustained increases of natriuresis and diuresis in asian patients with salt-sensitive hypertension / Wang, T.D.; Tan, R.S.; Lee, H.; Ihm, S.H. at all. // Journal of Hypertension: June 2015, - Volume 33 - Issue, doi: 10.1097/01.hjh.0000467685.39554.d4.23. Robert A. Fenton. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3 / Robert A. Fenton, Søren B. Poulsen, Samantha de la Mora Chavez at all. //  American Journal of Physiology - Renal Physiology Published 15 June 2015 Vol. 308 no. 12, F1409-F1420 DOI: 10.1152/ajprenal.00129.2015. 24. Sufei Yang. 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Экcпериментальное обоснование целесообразности использования 7,8-дизамещённых теофиллина как диуретических и нефрoпрoтектoрных средств. - Квалификационная научная работа на правах рукописи

В дисертаційній роботі обґрунтовано доцільність створення нових нефропротекторних засобів на основі 7,8-дизаміщених похідних теофіліну. Продемонстровано їх вищу фармакологічну активність за таку у деяких відомих діуретичних та нефропротекторних засобів (зокрема гіпотіазиду, канефрону, хофітолу). Було проведено аналітичний огляд вітчизняної та зарубіжної літератури за останні 10 років стосовно попередніх досліджень науковців з вивчення даного класу сполук. Проаналізовано номенклатуру лікарських препаратів з групи похідних ксантину, які вже існують на сучасному світовому фармацевтичному ринку, їх фармакологічні ефекти, механізми дії, завдяки яким ці ефекти реалізуються та сучасні підходи щодо фармакологічної регуляції екскреторної функції нирок, а також характеристика лікарських препаратів, які використовуються для корекції їх функціонального стану. На підставі літературних даних зроблено висновок щодо перспективності та актуальності подальших досліджень похідних теофіліну з метою використання їх для корекції ниркової патології. На першому етапі проведене дослідження гострої токсичності речовин у дослідах на мишах. За результатами дослідження встановлено, що сполуки, які вивчаються при oднoразoвoму внутрiшньoочеревиннoму введеннi мишам належать дo V клаcу практично не токсичних речовин (1001>LD50>3000 мг/кг). В результатi проведеного кoмп’ютернoгo PASS прoгнoзу імовірних видів фармакологічної активності 7,8-дизамiщених похідних теoфiлiну встановлено, щo бiльшicть cпoлук здатні виявляти дiуретичну, cалуретичну, cпазмoлiтичну, анальгетичну, прoтизапальну, антигiпoкcичну та інші види активностей. Новизна результатів проведеного дослідження захищена патентом України №116958 від 12.06.2017 р. «8-(4-бромобензиліден)гідразино-7-(4-метилбензил)- 1,3-диметилксантин, який виявляє спазмолітичну та протизапальну дії». За матеріалами досліджень видано інформаційний лист МОЗ України «Дослідження нефропротекторної дії нової субстанції серед похідних 7,8-дизаміщених теофіліну», який затверджено Укрмедпатентінформом (№ 183-2017 від 19.04.2017 р.). Теоретичні узагальнення щодо фармакологічної активності досліджень похідних 7,8-дизаміщених теофіліну впроваджені у навчальний процес на кафедрах: фармакології Національного фармацевтичного університету; експериментальної та клінічної фармакології з клінічною імунологією та алергологією ВДНЗУ «Українська медична стоматологічна академія»; біохімії Запорізького державного медичного університету.During the study, it was found that the benofillin normalizes the disturbance of the acid-base balance and the water-electrolyte exchange, has a restorative effect on the morphology of the renal tissues and, by activity, it is not inferior to the known drugs of nephroprotective action - canephrone and chophytol, and even some of them even outstrips them. Mechanisms of violations of water-electrolyte exchange in rats are found out. At the next stage, a study was conducted on the harmlessness of the benofillin in mice and rats by the rapid method recommended by I. V. Sanotsky in 5 animals in a series with each dose. During the experiment, the death of animals was not observed. Positive dynamics of changes in body weight of rats in the groups of application of the benofillin indicates absence of its toxic influence on the trophic processes of the animal's organism. The research of eventual of the damage activity of benifilin, on the lobe of the stomach and duodenum gut is carried out by the large nonlinear rats of the line of the citations by the method of J. Marazzi-Uberti. Consequently, benofilline, in difference from the acetyl-calcium carbonate, did not eliminate the ultrasonic action of ethyl alcohol. In the dissertation, the feasibility of the creation of new nephroprotective agents based on 7,8-disubstituted derivatives of theophylline has been substantiated. Their higher pharmacological activity is demonstrated for some of these known diuretic and nephroprotective agents (in particular, hypothiazide, canephrone, and chophytol). The novelty of the results of the study is protected by the Ukrainian patent №116958 dated 12/06/2017 "8-(4-bromobenzyliden) hydrazino-7- (4-methylbenzyl) - 1,3-dimethylxanthine, which exhibits antispasmodic and anti-inflammatory effects". According to the research materials, the information letter of the Ministry of Health of Ukraine "Research of nephroprotective action of a new substance among the derivatives 18 of 7,8-disubstituted theophylline" was issued, which was approved by Ukrmedpatentinform (No. 183-2017 of April 19, 2017). The results are implemented in the scientific and pedagogical process of pharmacology National University of Pharmacy; experimental and clinical pharmacology with clinical immunology and allergology HSEE of Ukraine «Ukrainian Medical Dentistry Academy»; biochemistry of Zaporizhzhya State Medical University

РИЗИК ВЕНОЗНОГО ТРОМБОЕМБОЛІЗМУ В ПАЦІЄНТІВ ЗАГАЛЬНОЇ ХІРУРГІЇ

The authors have performed an analysis of venous thromboembolism in 143 urgently operated patients and 13 pathoanatomical cards of patients whose cause of death was massive pulmonary embolism. It has been found out that the age, the duration of the operation, decompensated heart failure and postoperative immobilization are independent risk factors for venous thromboembolism.Проведен анализ венозного тромбоэмболизма в 143 ургентно оперированных и 13 патологоанатомических карт пациентов, умерших от массивной тромбоэмболии легочной артерии. Возраст, продолжительность операции, декомпенсированная сердечная недостаточность и послеоперационная иммобилизация являются независимыми факторами риска венозного тромбоэмболизма.Проведено аналіз венозного тромбоемболізму у 143 ургентно оперованих пацієнтів та 13 патологоанатомічних карт пацієнтів, причиною смерті яких була масивна тромбоемболія легеневої артерії. Виявлено, що вік, тривалість операції, декомпенсована серцева недостатність та післяопераційна іммобілізація є незалежними факторами ризику венозного тромбоемболізму

Modern treatment and evacuation aspects of the traumatological assistance provided to the wounded with the tibial gun shot injuries at the level of medical maintenance

Мета. Проаналізувати питому вагу вогнепальних поранень гомілки в структурі бойової хірургічної травми, визначити особливості лікувально-евакуаційних заходів при проведенні антитерористичної операції / операції об’єднаних сил на сході України. Матеріали і методи. Загальний масив дослідження становили 489 поранених у яких було 805 вогнепальних поранень гомілки з 2014 по 2018 роки під час проведення. Використано шкалу оцінки тяжкості бойової хірургічної травми. Результати. На підставі проведеного комплексного дослідження було встановлено, що поранення гомілки становили 23,95% в загальній структурі бойової травми кінцівок. У поранених з вогнепальними переломами кісток гомілки та відривами кінцівки на першому рівні медичного забезпечення необхідні тимчасова зупинка кровотечі, раннє накладання асептичної пов’язки, знеболення, іммобілізація підручними засобами та термінова медична евакуація на другий рівень медичної допомоги. На другому рівні переважно виконуються первинні хірургічні обробки рани (91,86%) та фасціотомія (44,19%). Важливим протишоковим заходом другого рівня є стабільне накладання стержневого апарату зовнішньої фіксації (43,02%), а також введення антибіотиків та правцевого анатоксину. На третьому та четвертому рівнях медичного забезпечення переважну більшість становили повторні хірургічні обробки ран, фасціотомії, реконструктивно-відновні оперативні втручання (рα9 балів) - допомогу надавати у скороченому обсязі за принципом контролю ушкоджень

Physicians' guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry

Background: Physicians' adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry. Methods and results: Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87–0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94–0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9–1.02; CV: SHR 0.98, 95% CI 0.96–1.01; and HF: SHR 0.99, 95% CI 0.96–1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). Conclusion: These results suggest that physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiolog