To access this material please log in or register

Register Authorize

Left ventricular dysfunction in hypertensive heart: Current view of the pathogenesis and treatment

Ovchinnikov A. G., Potekhina A. V., Ozhereljeva M. V., Ageev F. T.
Russian Cardiology Science and Production Center, 3rd Cherepkovskaya 15a, Moscow 121552, Russia

Keywords: arterial hypertension, left ventricle hypertrophy, diastolic dysfunction, heart failure with preserved ejection fraction, systolic dysfunction

DOI: 10.18087/cardio.2393

The article shows major mechanisms for development of left ventricular dysfunction in patients with hypertensive heart and provides major trends in the treatment of heart failure with preserved ejection fraction in the light of state-of-the art in its pathogenesis.
  1. Schmieder RE, Messerli FH. Hypertension and the heart. J Hum Hypertens. 2000;14 (10–11):597–604.
  2. Lavie CJ, Milani RV, Ventura HO, Messerli FH. Left ventricular geometry and mortality in patients >70 years of age with normal ejection fraction. Am J Cardiol. 2006;98 (10):1396–9. DOI:10.1016/j.amjcard.2006.06.037.
  3. Gardin JM, McClelland R, Kitzman D, Lima JA, Bommer W, Klopfenstein HS et al. M-mode echocardiographic predictors of sixto seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). Am J Cardiol. 2001;87 (9):1051–7.
  4. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322 (22):1561–6. DOI:10.1056/NEJM199005313222203.
  5. Meerson FZ. Compensatory hyperfunction of the heart and cardiac insufficiency. Circ Res. 1962;10:250–8.
  6. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E. Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA. 1982;79 (10):3310–4.
  7. Rapaport E. Natural history of aortic and mitral valve disease. Am J Cardiol. 1975;35 (2):221–7.
  8. Spirito P, Maron BJ, Bonow RO, Epstein SE. Occurrence and significance of progressive left ventricular wall thinning and relative cavity dilatation in hypertrophic cardiomyopathy. Am J Cardiol. 1987;60 (1):123–9.
  9. Rame JE, Ramilo M, Spencer N, Blewett C, Mehta SK, Dries DL et al. Development of a depressed left ventricular ejection fraction in patients with left ventricular hypertrophy and a normal ejection fraction. Am J Cardiol. 2004;93 (2):234–7.
  10. Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM et al. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol. 2004;43 (12):2207–15. DOI:10.1016/j.jacc.2003.11.064.
  11. Krishnamoorthy A, Brown T, Ayers CR, Gupta S, Rame JE, Patel PC et al. Progression from normal to reduced left ventricular ejection fraction in patients with concentric left ventricular hypertrophy after long-term follow-up. Am J Cardiol. 2011;108 (7):997–1001. DOI:10.1016/j.amjcard.2011.05.037.
  12. Drazner MH. The transition from hypertrophy to failure: how certain are we? Circulation. 2005;112 (7):936–8. DOI:10.1161/CIRCULATIONAHA.105.558734.
  13. Овчинников А. Г., Ожерельева М. В., Масенко В. П. Структурно-функциональные особенности течения компенсированного гипертонического сердца и факторы его неблагоприятного прогноза. Сердце: журнал для практикующих врачей. 2017;16(3):185–96. DOI:10.18087/rhj.2017.3.2347 [Ovchinnikov A. G., Ozherel`eva M. V., Masenko V. P. Strukturno-funkczional`ny`e osobennosti techeniya kompensirovannogo gipertonicheskogo serdcza i faktory` ego neblagopriyatnogo prognoza. Serdcze: zhurnal dlya praktikuyushhix vrachej. 2017;16 (3):185–96. DOI:10.18087/rhj.2017.3.2347].
  14. Mann DL, Felker GM. In: Heart failure: a companion to Braunwald’s heart disease [Internet]. 3‑d ed ed. Elsevier; 2016 [cited 2017]. p. 28–41, 361–75. Available from: https://www.clinicalkey.com/dura/browse/bookChapter/3‑s2.0‑C20120011829
  15. McMurray JJV, Carson PE, Komajda M, McKelvie R, Zile MR, Ptaszynska A et al. Heart failure with preserved ejection fraction: clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial. Eur J Heart Fail. 2008;10 (2):149–56. DOI:10.1016/j.ejheart.2007.12.010.
  16. Leite-Moreira AF, Correia-Pinto J, Gillebert TC. Afterload induced changes in myocardial relaxation: a mechanism for diastolic dysfunction. Cardiovasc Res. 1999;43 (2):344–53.
  17. Gillebert TC, Leite-Moreira AF, De Hert SG. Load dependent diastolic dysfunction in heart failure. Heart Fail Rev. 2000;5 (4):345–55.
  18. Arai M, Matsui H, Periasamy M. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res. 1994;74 (4):555–64.
  19. Palmer S, Kentish JC. Roles of Ca2+ and crossbridge kinetics in determining the maximum rates of Ca2+ activation and relaxation in rat and guinea pig skinned trabeculae. Circ Res. 1998;83(2):179–86.
  20. Helmes M, Trombitás K, Granzier H. Titin develops restoring force in rat cardiac myocytes. Circ Res. 1996;79 (3):619–26.
  21. Franssen C, González Miqueo A. The role of titin and extracellular matrix remodelling in heart failure with preserved ejection fraction. Neth Heart J. 2016;24 (4):259–67. DOI:10.1007/s12471‑016‑0812‑z.
  22. Zile MR, Baicu CF, Ikonomidis JS, Stroud RE, Nietert PJ, Bradshaw AD et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation. 2015;131 (14):1247–59. DOI:10.1161/CIRCULATIONAHA.114.013215.
  23. Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131 (6):550–9. DOI:10.1161/CIRCULATIONAHA.114.009625.
  24. Carroll JD, Lang RM, Neumann AL, Borow KM, Rajfer SI. The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy. Circulation. 1986;74 (4):815–25.
  25. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol. 1989;13 (7):1637–52.
  26. Weber KT, Sun Y, Campbell SE. Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides. Eur Heart J. 1995;16 Suppl N:12–8.
  27. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiological Reviews. 2007;87 (4):1285–342. DOI:10.1152/physrev.00012.2007.
  28. Lopez B, Gonzalez A, Querejeta R, Larman M, Díez J. Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure. J Am Coll Cardiol. 2006;48 (1):89–96. DOI:10.1016/j.jacc.2006.01.077.
  29. Rossi MA. Connective tissue skeleton in the normal left ventricle and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis. Med Sci Monit. 2001;7 (4):820–32.
  30. Tschope C, Van Linthout S. New insights in (inter) cellular mechanisms by heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2014;11 (4):436–44. DOI:10.1007/s11897‑014‑0219‑3.
  31. Paulus WJ, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62 (4):263–71. DOI:10.1016/j.jacc.2013.02.092.
  32. Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation. 2016;134 (1):73–90. DOI:10.1161/CIRCULATIONAHA.116.021884.
  33. Dhingra A, Garg A, Kaur S, Chopra S, Batra JS, Pandey A et al. Epidemiology of heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2014;11 (4):354–65. DOI:10.1007/s11897‑014‑0223‑7.
  34. Santhanakrishnan R, Chong JPC, Ng TP, Ling LH, Sim D, Leong KTG et al. Growth differentiation factor 15, ST2, highsensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. Eur J Heart Fail. 2012;14 (12):1338–47. DOI:10.1093/eurjhf/hfs130.
  35. Cheng JM, Akkerhuis KM, Battes LC, van Vark LC, Hillege HL, Paulus WJ et al. Biomarkers of heart failure with normal ejection fraction: a systematic review. Eur J Heart Fail. 2013;15 (12):1350–62. DOI:10.1093/eurjhf/hft106.
  36. Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tschöpe C et al. Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction. JACC Heart Fail. 2016;4 (4):312–24. DOI:10.1016/j.jchf.2015.10.007.
  37. LeWinter MM, Granzier HL. Cardiac titin and heart disease. J Cardiovasc Pharmacol. 2014;63 (3):207–12. DOI:10.1097/FJC.0000000000000007.
  38. Linke WA, Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res. 2014;114 (6):1052–68. DOI:10.1161/CIRCRESAHA.114.301286.
  39. van Heerebeek L, Hamdani N, Falcão-Pires I, Leite-Moreira AF, Begieneman MPV, Bronzwaer JGF et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation. 2012;126 (7):830–9. DOI:10.1161/CIRCULATIONAHA.111.076075.
  40. Westermann D, Lindner D, Kasner M, Zietsch C, Savvatis K, Escher F et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011;4 (1):44–52. DOI:10.1161/CIRCHEARTFAILURE.109.931451.
  41. Schussheim AE, Diamond JA, Phillips RA. Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension. Am J Cardiol. 2001;87 (1):61–5.
  42. Yurenev AP, Dyakonova HG, Novikov ID, Vitols A, Pahl L, Haynemann G et al. Management of essential hypertension in patients with different degrees of left ventricular hypertrophy. Multicenter trial. Am J Hypertens. 1992;5 (6 Pt 2):182S–189S.
  43. Cohen RA, Tong X. Vascular oxidative stress: the common link in hypertensive and diabetic vascular disease. J Cardiovasc Pharmacol. 2010;55 (4):308–16.
  44. Stritzke J, Markus MRP, Duderstadt S, Lieb W, Luchner A, Döring A et al. The aging process of the heart: obesity is the main risk factor for left atrial enlargement during aging the MONICA/KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study. J Am Coll Cardiol. 2009;54 (21):1982–9. DOI:10.1016/j.jacc.2009.07.034.
  45. Davis BR, Kostis JB, Simpson LM, Black HR, Cushman WC, Einhorn PT et al. Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Circulation. 2008;118 (22):2259–67. DOI:10.1161/CIRCULATIONAHA.107.762229.
  46. Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang M-H, Tousoulis D et al. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011;124 (3):335–45. DOI:10.1161/CIRCULATIONAHA.110.985150.
  47. Ramasubbu K, Estep J, White DL, Deswal A, Mann DL. Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy. J Am Coll Cardiol. 2008;51 (4):415–26. DOI:10.1016/j.jacc.2007.10.009.
  48. Fukuta H, Sane DC, Brucks S, Little WC. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation. 2005;112 (3):357–63. DOI:10.1161/CIRCULATIONAHA.104.519876.
  49. Nochioka K, Sakata Y, Miyata S, Miura M, Takada T, Tadaki S et al. Prognostic impact of statin use in patients with heart failure and preserved ejection fraction. Circ J. 2015;79 (3):574–82. DOI:10.1253/circj.CJ-14–0865.
  50. Alehagen U, Benson L, Edner M, Dahlström U, Lund LH. Association between use of statins and mortality in patients with heart failure and ejection fraction of ≥50. Circ Heart Fail. 2015;8 (5):862–70. DOI:10.1161/CIRCHEARTFAILURE.115.002143.
  51. Fukuta H, Goto T, Wakami K, Ohte N. The effect of statins on mortality in heart failure with preserved ejection fraction: a meta-analysis of propensity score analyses. Int J Cardiol. 2016;214:301–6. DOI:10.1016/j.ijcard.2016.03.186.
  52. Овчинников А. Г., Гаврюшина С. В., Агеев Ф. Т. Легочная гипертония, связанная с диастолической сердечной недостаточностью: патогенез, диагностика, лечение. Журнал Сердечная Недостаточность. 2016;17 (2):114–29. DOI:10.18087/rhfj.2016.2.2210 [Ovchinnikov A. G., Gavryushina S. V., Ageev F. T. Legochnaya gipertoniya, svyazannaya s diastolicheskoj serdechnoj nedostatochnost`yu: patogenez, diagnostika, lechenie. Zhurnal Serdechnaya Nedostatochnost`. 2016;17 (2):114–29. DOI:10.18087/rhfj.2016.2.2210].
  53. Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O et al. Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility In Vivo. Circulation. 2011;124 (25):2882–91. DOI:10.1161/CIRCULATIONAHA.111.048520.
  54. Shan X, Quaile MP, Monk JK, French B, Cappola TP, Margulies KB. Differential expression of PDE5 in failing and nonfailing human myocardium. Circulation: Heart Failure. 2012;5 (1):79–86. DOI:10.1161/CIRCHEARTFAILURE.111.961706.
  55. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11(2):214–22. DOI:10.1038/nm1175.
  56. Гаврюшина С. В., Овчинников А. Г., Агеев Ф. Т. Эффективность и безопасность терапии ингибитором фосфодиэстеразы типа 5 силденафилом у пациентов с диастолической сердечной недостаточностью и реактивной легочной гипертонией. Журнал Сердечная Недостаточность. 2016;17(3):173–80. DOI:10.18087/rhfj.2016.3.2225 [Gavryushina S. V., Ovchinnikov A. G., Ageev F. T. E`ffektivnost` i bezopasnost` terapii ingibitorom fosfodie`sterazy` tipa 5 sildenafilom u paczientov s diastolicheskoj serdechnoj nedostatochnost`yu i reaktivnoj legochnoj gipertoniej. Zhurnal Serdechnaya Nedostatochnost`. 2016;17 (3):173–80. DOI:10.18087/rhfj.2016.3.2225].
  57. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309 (12):1268–77. DOI:10.1001/jama.2013.2024.
  58. Hoendermis ES, Liu LCY, Hummel YM, van der Meer P, de Boer RA, Berger RMF et al. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J. 2015;36 (38):2565–73. DOI:10.1093/eurheartj/ehv336.
  59. Nagayama T, Hsu S, Zhang M, Koitabashi N, Bedja D, Gabrielson KL et al. Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. Journal of the American College of Cardiology. 2009;53(2):207–15. DOI:10.1016/j.jacc.2008.08.069.
  60. Chirinos JA, Segers P, Gupta AK, Swillens A, Rietzschel ER, De Buyzere ML et al. Time-varying myocardial stress and systolic pressure-stress relationship: role in myocardial-arterial coupling in hypertension. Circulation. 2009;119 (21):2798–807. DOI:10.1161/CIRCULATIONAHA.108.829366.
  61. Madamanchi C, Alhosaini H, Sumida A, Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Cardiol. 2014;176 (3):611–7. DOI:10.1016/j.ijcard.2014.08.007.
  62. Lee DI, Zhu G, Sasaki T, Cho G-S, Hamdani N, Holewinski R et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015;519 (7544):472–6. DOI:10.1038/nature14332.
  63. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. The Lancet. 2012;380 (9851):1387–95. DOI:10.1016/S0140–6736(12)61227–6.
  64. Brilla CG, Funck RC, Rupp H. Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation. 2000;102 (12):1388–93.
  65. Aronow WS, Kronzon I. Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol. 1993;71 (7):602–4.
  66. Cuocolo A, Storto G, Izzo R, Iovino GL, Damiano M, Bertocchi F et al. Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril. J Hypertens. 1999;17 (12 Pt 1):1759–66.
  67. Haber HL, Powers ER, Gimple LW, Wu CC, Subbiah K, Johnson WH et al. Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy. Circulation. 1994;89 (6):2616–25.
  68. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARMPreserved Trial. The Lancet. 2003;362 (9386):777–81. DOI:10.1016/S0140–6736(03)14285–7.
  69. Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359 (23):2456–67. DOI:10.1056/NEJMoa0805450.
  70. Cleland JGF, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. European Heart Journal. 2006;27(19):2338–45. DOI:10.1093/eurheartj/ehl250.
  71. Свирида О. Н., Овчинников А. Г., Агеев Ф. Т. Влияние кандесартана и его комбинации со спиронолактоном на диастолическую функцию левого желудочка и содержание биохимических маркеров баланса коллагена у пациентов с хронической сердечной недостаточностью и сохраненной систолической функцией левого желудочка. Журнал Сердечная Недостаточность. 2010;11(5):263–75 [Svirida O. N., Ovchinnikov A. G., Ageev F. T. Vliyanie kandesartana i ego kombinaczii so spironolaktonom na diastolicheskuyu funkcziyu levogo zheludochka i soderzhanie bioximicheskix markerov balansa kollagena u paczientov s xronicheskoj serdechnoj nedostatochnost`yu i soxranennoj sistolicheskoj funkcziej levogo zheludochka. Zhurnal Serdechnaya Nedostatochnost`. 2010;11 (5):263–75].
  72. Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015;131(1):34–42. DOI:10.1161/CIRCULATIONAHA.114.013255.
  73. Teekakirikul P, Eminaga S, Toka O, Alcalai R, Wang L, Wakimoto H et al. Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-β. J Clin Invest. 2010;120 (10):3520–9. DOI:10.1172/JCI42028.
  74. Lorts A, Schwanekamp JA, Baudino TA, McNally EM, Molkentin JD. Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-β pathway. Proc Natl Acad Sci USA. 2012;109 (27):10978–83. DOI:10.1073/pnas.1204708109.
  75. Huntgeburth M, Tiemann K, Shahverdyan R, Schlüter K-D, Schreckenberg R, Gross M–L et al. Transforming growth factor β₁ oppositely regulates the hypertrophic and contractile response to β-adrenergic stimulation in the heart. PLoS ONE. 2011;6(11):e26628. DOI:10.1371/journal.pone.0026628.
  76. Tan SM, Zhang Y, Wang B, Tan CYR, Zammit SC, Williams SJ et al. FT23, an orally active antifibrotic compound, attenuates structural and functional abnormalities in an experimental model of diabetic cardiomyopathy. Clin Exp Pharmacol Physiol. 2012;39 (8):650–6. DOI:10.1111/j.1440–1681.2012.05726.x.
  77. Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001;104 (13):1464–70.
  78. Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005;11 (3):191–5.
  79. Hartog JWL, Willemsen S, van Veldhuisen DJ, Posma JL, van Wijk LM, Hummel YM et al. Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure. Eur J Heart Fail. 2011;13 (8):899–908. DOI:10.1093/eurjhf/hfr067.
Ovchinnikov A. G., Potekhina A. V., Ozhereljeva M. V., Ageev F. T. Left ventricular dysfunction in hypertensive heart: Current view of the pathogenesis and treatment. Kardiologiia. 2017;57(S2):367–382

To access this material please log in or register

Register Authorize
Ru En