Mechanisms of exercise intolerance in patients with heart failure and preserved ejection fraction. Part I: The role of impairments in the left heart chambers
https://doi.org/10.18087/cardio.n394
Abstract
During exercise an increase in oxygen delivery to working muscles is achieved through well‑coordinated interaction of many organs and systems: the heart, lungs, blood vessels, skeletal muscles, and the autonomic nervous system. In heart failure with preserved left ventricular ejection fraction, all mechanisms involved in the normal exercise tolerance are impaired. In the first part of this review, the impairments of the left heart chambers are considered ‑ left ventricular diastolic dysfunction, the weakening of the contractile and chronotropic reserves, left atrium dysfunction; the possible ways of their medical correction are also presented.
About the Authors
A. G. Ovchinnikov
FSBO National Medical research center of cardiology of the Ministry of healthcare
of the Russian Federation
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
A. V. Potekhina
FSBO National Medical research center of cardiology of the Ministry of healthcare
of the Russian Federation
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
N. M. Ibragimova
FSBO National Medical research center of cardiology of the Ministry of healthcare
of the Russian Federation
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
E. A. Barabanova
I. M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Trubetskaya 8, bldg. 2, Moscow 119991
Russian Federation
Trubetskaya 8, bldg. 2, Moscow 119991
E. N. Yushchyuk
A. I. Evdokimov Moscow State University for Medicine and Dentistry
Russian Federation
Delegatskaya 20, Bld. 1, Moscow 127473
Russian Federation
Delegatskaya 20, Bld. 1, Moscow 127473
F. T. Ageev
FSBO National Medical research center of cardiology of the Ministry of healthcare
of the Russian Federation
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
Russian Federation
3rd Cherepkovskaya 15a, Moscow 121552
References
1. Bursi F, Weston SA, Redfeld MM, Jacobsen SJ, Pakhomov S, Nkomo VT et al. Systolic and Diastolic Heart Failure in the Community. JAMA. 2006;296(18):2209–16. DOI: 10.1001/jama.296.18.2209
2. Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nature Reviews Cardiology. 2014;11(9):507–15. DOI: 10.1038/nrcardio.2014.83
3. Straton JR, Levy WC, Cerqueira MD, Schwartz RS, Abrass IB. Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men. Circulation. 1994;89(4):1648–55. PMID: 8149532
4. Popović ZB, Prasad A, Garcia MJ, Arbab-Zadeh A, Borowski A, Dijk E et al. Relationship among diastolic intraventricular pressure gradients, relaxation, and preload: impact of age and ftness. American Journal of Physiology-Heart and Circulatory Physiology. 2006;290(4):H1454–9. DOI: 10.1152/ajpheart.00902.2005
5. Carrick-Ranson G, Hastings JL, Bhella PS, Shibata S, Fujimoto N, Palmer MD et al. Effect of healthy aging on lef ventricular relaxation and diastolic suction. American Journal of Physiology-Heart and Circulatory Physiology. 2012;303(3):H315–22. DOI: 10.1152/ajpheart.00142.2012
6. Borlaug BA, Redfeld MM, Melenovsky V, Kane GC, Karon BL, Jacobsen SJ et al. Longitudinal Changes in Lef Ventricular Stiffness: A Community-Based Study. Circulation: Heart Failure. 2013;6(5):944–52. DOI: 10.1161/CIRCHEARTFAILURE.113.000383
7. Wohlfahrt P, Redfeld MM, Lopez-Jimenez F, Melenovsky V, Kane GC, Rodeheffer RJ et al. Impact of General and Central Adiposity on Ventricular-Arterial Aging in Women and Men. JACC: Heart Failure. 2014;2(5):489–99. DOI: 10.1016/j.jchf.2014.03.014
8. Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension (Dallas, Tex.: 1979). 1996;27(4):849–53. PMID: 8613259
9. Rector TS, Carson PE, Anand IS, McMurray JJ, Zile MR, McKelvie RS et al. Assessment of Long-Term Effects of Irbesartan on Heart Failure with Preserved Ejection Fraction as Measured by the Minnesota Living With Heart Failure Questionnaire in the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial. Circulation: Heart Failure. 2012;5(2):217–25. DOI: 10.1161/CIRCHEARTFAILURE.111.964221
10. Zile MR, Kjellstrom B, Bennet T, Cho Y, Baicu CF, Aaron MF et al. Effects of Exercise on Lef Ventricular Systolic and Diastolic Properties in Patients With Heart Failure and a Preserved Ejection Fraction Versus Heart Failure and a Reduced Ejection Fraction. Circulation: Heart Failure. 2013;6(3):508–16. DOI: 10.1161/CIRCHEARTFAILURE.112.000216
11. Higginbotham MB, Morris KG, Williams RS, McHale PA, Coleman RE, Cobb FR. Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circulation Research. 1986;58(2):281–91. PMID: 3948345
12. Beck KC, Randolph LN, Bailey KR, Wood CM, Snyder EM, Johnson BD. Relationship between cardiac output and oxygen consumption during upright cycle exercise in healthy humans. Journal of Applied Physiology. 2006;101(5):1474–80. DOI: 10.1152/japplphysiol.00224.2006
13. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. European Heart Journal. 2011;32(6):670–9. DOI: 10.1093/eurheartj/ehq426
14. Rowell LB. Human cardiovascular control. – New York: Oxford University Press; 500 p. ISBN 978-0-19-507362-1
15. Chantler PD, Lakata EG, Najjar SS. Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise. Journal of Applied Physiology. 2008;105(4):1342–51. DOI: 10.1152/japplphysiol.90600.2008
16. Brubaker PH, Joo K-C, Stewart KP, Fray B, Moore B, Kitzman DW. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. Journal of Cardiopulmonary Rehabilitation. 2006;26(2):86–9. PMID: 16569976
17. Poliner LR, Dehmer GJ, Lewis SE, Parkey RW, Blomqvist CG, Willerson JT. Lef ventricular performance in normal subjects: a comparison of the responses to exercise in the upright and supine positions. Circulation. 1980;62(3):528–34. PMID: 7398013
18. Nonogi H, Hess OM, Riter M, Krayenbuehl HP. Diastolic properties of the normal lef ventricle during supine exercise. British Heart Journal. 1988;60(1):30–8. DOI: 10.1136/hrt.60.1.30
19. Cheng CP, Noda T, Nozawa T, Litle WC. Effect of heart failure on the mechanism of exercise-induced augmentation of mitral valve flow. Circulation Research. 1993;72(4):795–806. PMID: 8095187
20. Arai M, Matsui H, Periasamy M. Sarcoplasmic reticulum gene expres- sion in cardiac hypertrophy and heart failure. Circulation Research. 1994;74(4):555–64. PMID: 8137493
21. Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC et al. Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction. Circulation. 2006;114(20):2138–47. DOI: 10.1161/CIRCULATIO-NAHA.106.632745
22. Borbély A, Falcao-Pires I, van Heerebeek L, Hamdani N, Édes I, Gavina C et al. Hypophosphorylation of the Stiff N2B Titin Isoform Raises Cardiomyocyte Resting Tension in Failing Human Myocardium. Circulation Research. 2009;104(6):780–6. DOI: 10.1161/CIRCRESAHA.108.193326
23. Leite-Moreira AM, Almeida-Coelho J, Neves JS, Pires AL, Ferreira-Martins J, Castro-Ferreira R et al. Stretch-induced compliance: a novel adaptive biological mechanism following acute cardiac load. Cardiovascular Research. 2018;114(5):656–67. DOI: 10.1093/cvr/cvy026
24. Hidalgo C, Granzier H. Tuning the molecular giant titin through phosphorylation: Role in health and disease. Trends in Cardiovascular Medicine. 2013;23(5):165–71. DOI: 10.1016/j.tcm.2012.10.005
25. Paulus WJ. Culprit Mechanism(s) for Exercise Intolerance in Heart Failure With Normal Ejection Fraction⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology. Journal of the American College of Cardiology. 2010;56(11):864–6. DOI: 10.1016/j.jacc.2010.04.041
26. Borlaug BA, Jaber WA, Ommen SR, Lam CSP, Redfeld MM, Nishimura R. Diastolic relaxation and compliance reserve during dynamic exercise in heart failure with preserved ejection fraction. Heart. 2011;97(12):964–9. DOI: 10.1136/hrt.2010.212787
27. Hay I, Rich J, Ferber P, Burkhoff D, Maurer MS. Role of impaired myocardial relaxation in the production of elevated lef ventricular flling pressure. American Journal of Physiology-Heart and Circulatory Physiology. 2005;288(3):H1203–8. DOI: 10.1152/ajpheart.00681.2004
28. Tan YT, Wenzelburger F, Lee E, Heatlie G, Leyva F, Patel K et al. The Pathophysiology of Heart Failure With Normal Ejection Fraction. Journal of the American College of Cardiology. 2009;54(1):36–46. DOI: 10.1016/j.jacc.2009.03.037
29. 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
30. Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW. Determinants of Exercise Intolerance in Elderly Heart Failure Patients With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2011;58(3):265–74. DOI: 10.1016/j.jacc.2011.02.055
31. Shibata S, Hastings JL, Prasad A, Fu Q, Bhella PS, Pacini E et al. Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism. Journal of Applied Physiology. 2011;110(4):964–71. DOI: 10.1152/japplphysiol.00826.2010
32. Abudiab MM, Redfeld MM, Melenovsky V, Olson TP, Kass DA, Johnson BD et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. European Journal of Heart Failure. 2013;15(7):776–85. DOI: 10.1093/eurjhf/hf026
33. Borlaug BA, Nishimura R, Sorajja P, Lam CSP, Redfeld MM. Exercise Hemodynamics Enhance Diagnosis of Early Heart Failure With Preserved Ejection Fraction. Circulation: Heart Failure. 2010;3(5):588–95. DOI: 10.1161/CIRCHEARTFAILURE.109.930701
34. Ovchinnikov A.G., Azizova A.G., Masenko V.P., Shatalina L.S., Ageev F.T. The effect of loop diuretics on the clinical course, the flling pressure of the lef ventricle in patients with compensated NSFW and high flling pressure of the LV. Russian Heart Failure Journal. 2012;13 (6):320–33. [Russian: Овчинников А.Г., Азизова А.Г., Масенко В.П., Шаталина Л.С., Агеев Ф.Т. Влияние петлевых диуретиков на клиническое течение, давление наполнения левого желудочка у больных с компенсированной СНСФВ и высоким давлением наполнения ЛЖ. Журнал Сердечная Недостаточность. 2012;13(6):320-33]
35. Hasenfuß G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F et al. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. The Lancet. 2016;387(10025):1298–304. DOI: 10.1016/S0140-6736(16)00704-2
36. 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. Journal of the American College of Cardiology. 2013;62(4):263–71. DOI: 10.1016/j.jacc.2013.02.092
37. Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O et al. Sildenafl 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
38. Ovchinnikov AG, Potekhina AV, Gavryushina SV, Ageev FT. P2138. Sildenafl improves functional capacity and exercise hemodynamics in patients with heart failure with preserved lef ventricular ejection fraction and predominantly combined pre- and post-capillary pulmonary hypertension. European Journal of Heart Failure. 2018;20(Suppl 1):567. DOI: 10.1002/ejhf.1197
39. Khan AM, Cheng S, Magnusson M, Larson MG, Newton-Cheh C, McCabe EL et al. Cardiac Natriuretic Peptides, Obesity, and Insulin Resistance: Evidence from Two Community-Based Studies. The Journal of Clinical Endocrinology & Metabolism. 2011;96(10):3242–9. DOI: 10.1210/jc.2011-1182
40. 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
41. Svirida O.N., Ovchinnikov A.G., Ageev F.T. Influence of candesartan and its combination with spironolactone on lef ventricular diastolic function and level of collagen balance’s biochemical markers in patients with chronic heart failure and preserved lef ventricular systolic function. Russian Heart Failure Journal. 2010;11(5):263–75. [Russian: 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]
42. Kosmala W, Rojek A, Przewlocka-Kosmala M, Wright L, Mysiak A, Marwick TH. Effect of Aldosterone Antagonism on Exercise Tolerance in Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2016;68(17):1823–34. DOI: 10.1016/j.jacc.2016.07.763
43. Kass DA, Shapiro EP, Kawaguchi M, Caprioti 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. PMID: 11571237
44. Phan T, Abozguia K, Nallur Shivu G, Ahmed I, Leyva F, Patel K et al. Increased Atrial Contribution to Lef Ventricular Filling Compensates for Impaired Early Filling During Exercise in Heart Failure With Preserved Ejection Fraction. Journal of Cardiac Failure. 2009;15(10):890–7. DOI: 10.1016/j.cardfail.2009.06.440
45. Tan YT, Wenzelburger F, Lee E, Nightingale P, Heatlie G, Leyva F et al. Reduced lef atrial function on exercise in patients with heart failure and normal ejection fraction. Heart. 2010;96(13):1017–23. DOI: 10.1136/hrt.2009.189118
46. Azizova A.G., Ovchinnikov A.G., Ageev F.T. Comparative study of Torasemide vs. Furosemide effects on clinical status and diastolic function of the lef ventricle in patients with compensated heart failure and high ventricular flling pressure. Russian Heart Failure Journal. 2011;12 (6):326–32. [Russian: Азизова А.Г., Овчинников А.Г., Агеев Ф.Т. Сравнительное влияние торасемида и фуросемида на клинический статус и диастолическую функцию левого желудочка у больных с компенсированной сердечной недостаточностью и высоким давлением наполнения левого желудочка. Журнал Сердечная Недостаточность. 2011;12(6):326-32]
47. Freed BH, Daruwalla V, Cheng JY, Aguilar FG, Beussink L, Choi A et al. Prognostic Utility and Clinical Signifcance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Lef Atrial Strain. Circulation: Cardiovascular Imaging. 2016;9(3):e003754. DOI: 10.1161/CIRCIMAGING.115.003754
48. Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Clagget B, Pieske B et al. Impaired Systolic Function by Strain Imaging in Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2014;63(5):447–56. DOI: 10.1016/j.jacc.2013.09.052
49. Shah AM, Clagget B, Sweitzer NK, Shah SJ, Anand IS, Liu L et al. Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. Circulation. 2015;132(5):402–14. DOI: 10.1161/CIRCULATIONAHA.115.015884
50. Phan T, Abozguia K, Nallur Shivu G, Mahadevan G, Ahmed I, Williams L et al. Heart Failure With Preserved Ejection Fraction Is Characterized by Dynamic Impairment of Active Relaxation and Contraction of the Lef Ventricle on Exercise and Associated With Myocardial Energy Defciency. Journal of the American College of Cardiology. 2009;54(5):402–9. DOI: 10.1016/j.jacc.2009.05.012
51. Borlaug BA, Olson TP, Lam CSP, Flood KS, Lerman A, Johnson BD et al. Global Cardiovascular Reserve Dysfunction in Heart Failure with Preserved Ejection Fraction. Journal of the American College of Cardiology. 2010;56(11):845–54. DOI: 10.1016/j.jacc.2010.03.077
52. Hundley WG, Kitzman DW, Morgan TM, Hamilton CA, Darty SN, Stewart KP et al. Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. Journal of the American College of Cardiology. 2001;38(3):796–802. PMID: 11527636
53. Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfeld MM. Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction. Circulation. 2015;131(6):550–9. DOI: 10.1161/CIRCULATIO-NAHA.114.009625
54. Liu CP, Ting CT, Lawrence W, Maughan WL, Chang MS, Kass DA. Diminished contractile response to increased heart rate in intact human lef ventricular hypertrophy. Systolic versus diastolic determinants. Circulation. 1993;88(4 Pt 1):1893–906. PMID: 8403335
55. Ohara T, Niebel CL, Stewart KC, Charonko JJ, Pu M, Vlachos PP et al. Loss of Adrenergic Augmentation of Diastolic Intra-LV Pressure Difference in Patients With Diastolic Dysfunction. JACC: Cardiovascular Imaging. 2012;5(9):861–70. DOI: 10.1016/j.jcmg.2012.05.013
56. Smith CS, Botomley PA, Schulman SP, Gerstenblith G, Weiss RG. Altered Creatine Kinase Adenosine Triphosphate Kinetics in Failing Hypertrophied Human Myocardium. Circulation. 2006;114(11):1151–8. DOI: 10.1161/CIRCULATIONAHA.106.613646
57. Phan T, Shivu GN, Abozguia K, Davies C, Nassimizadeh M, Jimenez D et al. Impaired Heart Rate Recovery and Chronotropic Incompetence in Patients With Heart Failure With Preserved Ejection Fraction. Circulation: Heart Failure. 2010;3(1):29–34. DOI: 10.1161/CIRCHEARTFAILURE.109.877720
58. Huang P-H. Comparison of endothelial vasodilator function, inflammatory markers, and N-terminal pro-brain natriuretic peptide in patients with or without chronotropic incompetence to exercise test. Heart. 2006;92(5):609–14. DOI: 10.1136/hrt.2005.064147
59. Pandey A, Khera R, Park B, Haykowsky M, Borlaug BA, Lewis GD et al. Relative Impairments in Hemodynamic Exercise Reserve Parameters in Heart Failure With Preserved Ejection Fraction. JACC: Heart Failure. 2018;6(2):117–26. DOI: 10.1016/j.jchf.2017.10.014
60. Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka-Kosmala M, Marwick TH. Effect of If-Channel Inhibition on Hemodynamic Status and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2013;62(15):1330–8. DOI: 10.1016/j.jacc.2013.06.043
61. Pal N, Sivaswamy N, Mahmod M, Yavari A, Rudd A, Singh S et al. Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction. Circulation. 2015;132(18):1719–25. DOI: 10.1161/CIRCULATIONAHA.115.017119
62. Zakeri R, Chamberlain AM, Roger VL, Redfeld MM. Temporal Relationship and Prognostic Signifcance of Atrial Fibrillation in Heart Failure Patients With Preserved Ejection Fraction: A Community-Based Study. Circulation. 2013;128(10):1085–93. DOI: 10.1161/CIRCULATIONAHA.113.001475
63. Melenovsky V, Hwang S-J, Lin G, Redfeld MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. European Heart Journal. 2014;35(48):3452–62. DOI: 10.1093/eurheartj/ehu193
64. Santhanakrishnan R, Wang N, Larson MG, Magnani JW, McManus DD, Lubitz SA et al. Atrial fbrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction. Circulation. 2016;133(5):484–92. DOI: 10.1161/CIRCULATIONAHA.115.018614
65. Elliot AD, Mahajan R, Pathak RK, Lau DH, Sanders P. Exercise Training and Atrial Fibrillation: Further Evidence for the Importance of Lifestyle Change. Circulation. 2016;133(5):457–9. DOI: 10.1161/CIRCULATIONAHA.115.020800
66. Machino-Ohtsuka T, Seo Y, Ishizu T, Sugano A, Atsumi A, Yamamoto M et al. Efcacy, Safety, and Outcomes of Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure With Preserved Ejection Fraction. Journal of the American College of Cardiology. 2013;62(20):1857–65. DOI: 10.1016/j.jacc.2013.07.020
67. Glezeva N, Baugh JA. Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target. Heart Failure Reviews. 2014;19(5):681–94. DOI: 10.1007/s10741-013-9405-8
68. Van Tassell BW, Arena R, Biondi-Zoccai G, McNair Canada J, Oddi C, Abouzaki NA et al. Effects of Interleukin-1 Blockade With Anakinra on Aerobic Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction (from the D-HART Pilot Study). The American Journal of Cardiology. 2014;113(2):321–7. DOI: 10.1016/j.amjcard.2013.08.047
69. Van Tassell BW, Trankle CR, Canada JM, Carbone S, Buckley L, Kadariya D et al. IL-1 Blockade in Patients With Heart Failure with Preserved Ejection Fraction: Results From DHART2. Circulation: Heart Failure. 2018;11(8):e005036. DOI: 10.1161/CIRCHEARTFAILURE.118.005036
70. Haudek SB, Cheng J, Du J, Wang Y, Hermosillo-Rodriguez J, Trial J et al. Monocytic fbroblast precursors mediate fbrosis in angiotensin-II-induced cardiac hypertrophy. Journal of Molecular and Cellular Cardiology. 2010;49(3):499–507. DOI: 10.1016/j.yjmcc.2010.05.005
71. Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K et al. Hypertensive Myocardial Fibrosis and Diastolic Dysfunction: Another Model of Inflammation? Hypertension. 2004;43(4):739–45. DOI: 10.1161/01.HYP.0000118584.33350.7d
72. 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. Journal of the American College of Cardiology. 2008;51(4):415–26. DOI: 10.1016/j.jacc.2007.10.009
73. Fukuta H, Sane DC, Brucks S, Litle 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
74. 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. Circulation Journal: Ofcial Journal of the Japanese Circulation Society. 2015;79(3):574–82. DOI: 10.1253/circj.CJ-14-0865
75. 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. Circulation. Heart Failure. 2015;8(5):862–70. DOI: 10.1161/CIRCHEARTFAILURE.115.002143
76. Ovchinnikov A.G., Ojerelyeva M.V., Ageev F.T. Hypertensive lef ventricular hypertrophy is a risk factor for the development of a HFPEF but not a depressed lef ventricular ejection fraction within eight years. European Journal of Heart Failure. 2017;19(S1):328
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For citations:
Ovchinnikov A.G., Potekhina A.V., Ibragimova N.M., Barabanova E.A., Yushchyuk E.N., Ageev F.T. Mechanisms of exercise intolerance in patients with heart failure and preserved ejection fraction. Part I: The role of impairments in the left heart chambers. Kardiologiia. 2019;59(6S):4-16. (In Russ.) https://doi.org/10.18087/cardio.n394
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