Статья
Роль ингибиторов неприлизина в лечении сердечной недостаточности с сохраненной фракцией выброса
Клиническое и гемодинамическое ухудшение при сердечной недостаточности с сохраненной фракцией выброса (СНсФВ) во многом связано с прогрессией диастолической дисфункции левого желудочка (ЛЖ). Ключевую роль в нормальном поддержании диастолической функции играет высокий уровень активности внутриклеточной сигнальной оси циклический гуанил-монофосфат–протеинкиназа G, активность которой при СНсФВ существенно снижена. Повысить активность этой оси можно путем увеличения биодоступности натрийуретических пептидов (НУП) с помощью блокады фермента нейтральной эндопептидазы (неприлизина), ответственной за разрушение НУП. В обзоре представлены имеющиеся экспериментальные и клинические данные по применению ингибиторов неприлизина при СНсФВ, рассмотрены перспективы этого способа лечения.
1. Vaduganathan M, Michel A, Hall K, Mulligan C, Nodari S, Shah SJ et al. Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review. European Journal of Heart Failure. 2016;18(1):54–65. DOI: 10.1002/ejhf.442
2. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC et al. Forecasting the Impact of Heart Failure in the United States: A Policy Statement From the American Heart Association. Circulation: Heart Failure. 2013;6(3):606–19. DOI: 10.1161/HHF.0b013e318291329a
3. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126(1):65–75. DOI: 10.1161/CIRCULATIONAHA.111.080770
4. Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ et al. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation. 2009;119(24):3070–7. DOI: 10.1161/CIRCULATIONAHA.108.815944
5. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. New England Journal of Medicine. 2006;355(3):251–9. DOI: 10.1056/NEJMoa052256
6. 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
7. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nature Reviews Cardiology. 2017;14(10):591–602. DOI: 10.1038/nrcardio.2017.65
8. Dhingra A, Garg A, Kaur S, Chopra S, Batra JS, Pandey A et al. Epidemiology of heart failure with preserved ejection fraction. Current Heart Failure Reports. 2014;11(4):354–65. DOI: 10.1007/s11897-014-0223-7
9. 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
10. Hofmann F. A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology. Basic Research in Cardiology. 2018;113(4):31. DOI: 10.1007/s00395-018-0690-1
11. LeWinter MM, Granzier HL. Cardiac titin and heart disease. Journal of Cardiovascular Pharmacology. 2014;63(3):207–12. DOI: 10.1097/FJC.0000000000000007
12. Colliva A, Braga L, Giacca M, Zacchigna S. Endothelial cell– cardiomyocyte crosstalk in heart development and disease. The Journal of Physiology. 2020;598(14):2923–39. DOI: 10.1113/JP276758
13. Kong Q, Blanton RM. Protein Kinase G I and Heart Failure: Shifting Focus From Vascular Unloading to Direct Myocardial Antiremodeling Effects. Circulation: Heart Failure. 2013;6(6):1268–83. DOI: 10.1161/CIRCHEARTFAILURE.113.000575
14. 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
15. 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
16. Hamdani N, Bishu KG, von Frieling-Salewsky M, Redfield MM, Linke WA. Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction. Cardiovascular Research. 2013;97(3):464–71. DOI: 10.1093/cvr/cvs353
17. 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
18. Krüger M, Linke WA. Titin-based mechanical signalling in normal and failing myocardium. Journal of Molecular and Cellular Cardiology. 2009;46(4):490–8. DOI: 10.1016/j.yjmcc.2009.01.004
19. 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. Nature Medicine. 2005;11(2):214–22. DOI: 10.1038/nm1175
20. Burke RM, Lighthouse JK, Mickelsen DM, Small EM. Sacubitril/Valsartan Decreases Cardiac Fibrosis in Left Ventricle Pressure Overload by Restoring PKG Signaling in Cardiac Fibroblasts. Circulation: Heart Failure. 2019;12(4):e005565. DOI: 10.1161/CIRCHEARTFAILURE.118.005565
21. Sandner P, Stasch JP. Antifibrotic effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence. Respiratory Medicine. 2017;122(Suppl 1):S1–9. DOI: 10.1016/j.rmed.2016.08.022
22. Methner C, Buonincontri G, Hu C-H, Vujic A, Kretschmer A, Sawiak S et al. Riociguat Reduces Infarct Size and Post-Infarct Heart Failure in Mouse Hearts: Insights from MRI/PET Imaging. PLoS ONE. 2013;8(12):e83910. DOI: 10.1371/journal.pone.0083910
23. Park M, Sandner P, Krieg T. cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway. Basic Research in Cardiology. 2018;113(4):24. DOI: 10.1007/s00395-018-0679-9
24. Yoshimura M, Yasue H, Okumura K, Ogawa H, Jougasaki M, Mukoyama M et al. Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure. Circulation. 1993;87(2):464–9. DOI: 10.1161/01.CIR.87.2.464
25. Heart failure: scientific principles and clinical practice. Poole-Wilson PA, editor -Edinburgh: Churchill Livingstone;1997. - 929 p.. ISBN 978-0-443-07501-8
26. Rodeheffer RJ, Tanaka I, Imada T, Hollister AS, Robertson D, Inagami T. Atrial pressure and secretion of atrial natriuretic factor into the human central circulation. Journal of the American College of Cardiology. 1986;8(1):18–26. DOI: 10.1016/S0735-1097(86)80086-9
27. Yan W, Wu F, Morser J, Wu Q. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Proceedings of the National Academy of Sciences. 2000;97(15):8525–9. DOI: 10.1073/pnas.150149097
28. Hunt PJ, Yandle TG, Nicholls MG, Richards AM, Espiner EA. The Amino-Terminal Portion of Pro-Brain Natriuretic Peptide (ProBNP) Circulates in Human Plasma. Biochemical and Biophysical Research Communications. 1995;214(3):1175–83. DOI: 10.1006/bbrc.1995.2410
29. Dunn BR, Ichikawa I, Pfeffer JM, Troy JL, Brenner BM. Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat. Circulation Research. 1986;59(3):237–46. DOI: 10.1161/01.RES.59.3.237
30. Maack T. Role of atrial natriuretic factor in volume control. Kidney International. 1996;49(6):1732–7. DOI: 10.1038/ki.1996.257
31. Espiner EA, Richards AM, Nicholls MG. Physiology of Natriuretic Peptides.. In: Endocrinology of Cardiovascular Function. Series Title: Endocrine Updates.. Levin ER, Nadler JL, editors -Boston, MA: Springer US;1998.
32. Lugnier C, Meyer A, Charloux A, Andrès E, Gény B, Talha S. The Endocrine Function of the Heart: Physiology and Involvements of Natriuretic Peptides and Cyclic Nucleotide Phosphodiesterases in Heart Failure. Journal of Clinical Medicine. 2019;8(10):1746. DOI: 10.3390/jcm8101746
33. ISSN 0022-9040. Кардиология. 2020;60(11). DOI: 10.18087/cardio.2020.11.n1352
34. Forte, Madonna, Schiavon, Valenti, Versaci, Zoccai et al. Cardiovascular Pleiotropic Effects of Natriuretic Peptides. International Journal of Molecular Sciences. 2019;20(16):3874. DOI: 10.3390/ijms20163874
35. Kapoun AM. B-Type Natriuretic Peptide Exerts Broad Functional Opposition to Transforming Growth Factor- in Primary Human Cardiac Fibroblasts: Fibrosis, Myofibroblast Conversion, Proliferation, and Inflammation. Circulation Research. 2004;94(4):453–61. DOI: 10.1161/01.RES.0000117070.86556.9F
36. Wang D, Gladysheva IP, Fan T-HM, Sullivan R, Houng AK, Reed GL. Atrial Natriuretic Peptide Affects Cardiac Remodeling, Function, Heart Failure, and Survival in a Mouse Model of Dilated Cardiomyopathy. Hypertension. 2014;63(3):514–9. DOI: 10.1161/HYPERTENSIONAHA.113.02164
37. Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M et al. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proceedings of the National Academy of Sciences. 2000;97(8):4239–44. DOI: 10.1073/pnas.070371497
38. Moyes AJ, Khambata RS, Villar I, Bubb KJ, Baliga RS, Lumsden NG et al. Endothelial C-type natriuretic peptide maintains vascular homeostasis. Journal of Clinical Investigation. 2014;124(9):4039–51. DOI: 10.1172/JCI74281
39. Buttgereit J, Shanks J, Li D, Hao G, Athwal A, Langenickel TH et al. C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function. Cardiovascular Research. 2016;112(3):637–44. DOI: 10.1093/cvr/cvw184
40. Cardarelli R, Lumicao TG. B-type Natriuretic Peptide: A Review of Its Diagnostic, Prognostic, and Therapeutic Monitoring Value in Heart Failure for Primary Care Physicians. The Journal of the American Board of Family Medicine. 2003;16(4):327–33. DOI: 10.3122/jabfm.16.4.327
41. Rubattu S, Volpe M. Natriuretic Peptides in the Cardiovascular System: Multifaceted Roles in Physiology, Pathology and Therapeutics. International Journal of Molecular Sciences. 2019;20(16):3991. DOI: 10.3390/ijms20163991
42. Januzzi JL. NT-proBNP testing for diagnosis and shortterm prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: The International Collaborative of NT-proBNP Study. European Heart Journal. 2005;27(3):330–7. DOI: 10.1093/eurheartj/ehi631
43. Gaggin HK, Mohammed AA, Bhardwaj A, Rehman SU, Gregory SA, Weiner RB et al. Heart Failure Outcomes and Benefits of NTproBNP-Guided Management in the Elderly: Results From the Prospective, Randomized ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study. Journal of Cardiac Failure. 2012;18(8):626–34. DOI: 10.1016/j.cardfail.2012.05.005
44. Ichiki T, Boerrigter G, Huntley BK, Sangaralingham SJ, McKie PM, Harty GJ et al. Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2013;304(2):R102–9. DOI: 10.1152/ajpregu.00233.2012
45. Tripathi R, Wang D, Sullivan R, Fan T-HM, Gladysheva IP, Reed GL. Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development. Hypertension. 2016;67(2):362–7. DOI: 10.1161/HYPERTENSIONAHA.115.06300
46. Dong N, Chen S, Yang J, He L, Liu P, Zheng D et al. Plasma Soluble Corin in Patients With Heart Failure. Circulation: Heart Failure. 2010;3(2):207– 11. DOI: 10.1161/CIRCHEARTFAILURE.109.903849
47. Ibebuogu UN, Gladysheva IP, Houng AK, Reed GL. Decompensated Heart Failure Is Associated With Reduced Corin Levels and Decreased Cleavage of Pro–Atrial Natriuretic Peptide. Circulation: Heart Failure. 2011;4(2):114–20. DOI: 10.1161/CIRCHEARTFAILURE.109.895581
48. Zhou X, Chen J-C, Liu Y, Yang H, Du K, Kong Y et al. Plasma Corin as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure. JACC: Heart Failure. 2016;4(8):664–9. DOI: 10.1016/j.jchf.2016.03.006
49. Huntley BK, Sandberg SM, Heublein DM, Sangaralingham SJ, Burnett JC, Ichiki T. Pro–B-Type Natriuretic Peptide-1-108 Processing and Degradation in Human Heart Failure. Circulation: Heart Failure. 2015;8(1):89–97. DOI: 10.1161/CIRCHEARTFAILURE.114.001174
50. Fuller F, Porter JG, Arfsten AE, Miller J, Schilling JW, Scarborough RM et al. Atrial natriuretic peptide clearance receptor. Complete sequence and functional expression of cDNA clones. The Journal of Biological Chemistry. 1988;263(19):9395–401. PMID: 2837487
51. Chen HH. Heart Failure: A State of Brain Natriuretic Peptide Deficiency or Resistance or Both! Journal of the American College of Cardiology. 2007;49(10):1089–91. DOI: 10.1016/j.jacc.2006.12.013
52. Martinez-Rumayor A, Richards AM, Burnett JC, Januzzi JL. Biology of the Natriuretic Peptides. The American Journal of Cardiology. 2008;101(3):S3–8. DOI: 10.1016/j.amjcard.2007.11.012
53. 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
54. Núñez J, Núñez E, Barallat J, Bodí V, Miñana G, Pastor MC et al. Serum Neprilysin and Recurrent Admissions in Patients With Heart Failure. Journal of the American Heart Association. 2017;6(8):e005712. DOI: 10.1161/JAHA.117.005712
55. Hobbs RE, Mills RM. Therapeutic potential of nesiritide (recombinant b- type natriuretic peptide) in the treatment of heart failure. Expert Opinion on Investigational Drugs. 1999;8(7):1063–72. DOI: 10.1517/13543784.8.7.1063
56. Marcus LS, Hart D, Packer M, Yushak M, Medina N, Danziger RS et al. Hemodynamic and Renal Excretory Effects of Human Brain Natriuretic Peptide Infusion in Patients With Congestive Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Crossover Trial. Circulation. 1996;94(12):3184–9. DOI: 10.1161/01.CIR.94.12.3184
57. Mills RM, LeJemtel TH, Horton DP, Liang C, Lang R, Silver MA et al. Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure. Journal of the American College of Cardiology. 1999;34(1):155–62. DOI: 10.1016/S0735-1097(99)00184-9
58. Elkayam U, Akhter MW, Tummala P, Khan S, Singh H. Nesiritide: A New Drug for the Treatment of Decompensated Heart Failure. Journal of Cardiovascular Pharmacology and Therapeutics. 2002;7(3):181–94. DOI: 10.1177/107424840200700308
59. Colbert K, Greene MH. Nesiritide (Natrecor): a new treatment for acutely decompensated congestive heart failure. Critical Care Nursing Quarterly. 2003;26(1):40–4. DOI: 10.1097/00002727-200301000-00007
60. Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure: A Pooled Analysis of Randomized Controlled Trials. JAMA. 2005;293(15):1900–5. DOI: 10.1001/jama.293.15.1900
61. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure. Circulation. 2005;111(12):1487–91. DOI: 10.1161/01.CIR.0000159340.93220.E4
62. O’Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V et al. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure. New England Journal of Medicine. 2011;365(1):32–43. DOI: 10.1056/NEJMoa1100171
63. Chen HH, Glockner JF, Schirger JA, Cataliotti A, Redfield MM, Burnett JC. Novel Protein Therapeutics for Systolic Heart Failure: chronic subcutaneous B-type natriuretic peptide. Journal of the American College of Cardiology. 2012;60(22):2305–12. DOI: 10.1016/j.jacc.2012.07.056
64. Martin FL, Stevens TL, Cataliotti A, Schirger JA, Borgeson DD, Redfield MM et al. Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure. Kidney International. 2005;67(5):1723–30. DOI: 10.1111/j.1523-1755.2005.00269.x
65. Richards AM, Wittert GA, Crozier IG, Espiner EA, Yandle TG, Ikram H et al. Chronic inhibition of endopeptidase 24.11 in essential hypertension: evidence for enhanced atrial natriuretic peptide and angiotensin II. Journal of Hypertension. 1993;11(4):407–16. DOI: 10.1097/00004872-199304000-00011
66. Ando S, Rahman MA, Butler GC, Senn BL, Floras JS. Comparison of Candoxatril and Atrial Natriuretic Factor in Healthy Men: Effects on Hemodynamics, Sympathetic Activity, Heart Rate Variability, and Endothelin. Hypertension. 1995;26(6):1160–6. DOI: 10.1161/01.HYP.26.6.1160
67. Northridge DB, Currie PF, Newby DE, McMurray JJV, Ford M, Boon NA et al. Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure. European Journal of Heart Failure. 1999;1(1):67–72. DOI: 10.1016/S1388-9842(98)00003-8
68. Rouleau JL, Pfeffer MA, Stewart DJ, Isaac D, Sestier F, Kerut EK et al. Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial. The Lancet. 2000;356(9230):615–20. DOI: 10.1016/S0140-6736(00)02602-7
69. Packer M, Califf RM, Konstam MA, Krum H, McMurray JJ, Rouleau J-L et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106(8):920–6. DOI: 10.1161/01.cir.0000029801.86489.50
70. McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR et al. Angiotensin–niprilysin Inhibition versus enalapril in heart failure. New England Journal of Medicine. 2014;371(11):993–1004. DOI: 10.1056/NEJMoa1409077
71. Januzzi JL, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K et al. Association of Change in N-Terminal Pro–B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. JAMA. 2019;322(11):1–11. DOI: 10.1001/jama.2019.12821
72. Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K et al. Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure. New England Journal of Medicine. 2019;380(6):539–48. DOI: 10.1056/NEJMoa1812851
73. Wachter R, Senni M, Belohlavek J, Straburzynska‐Migaj E, Witte KK, Kobalava Z et al. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. European Journal of Heart Failure. 2019;21(8):998–1007. DOI: 10.1002/ejhf.1498
74. Kang D-H, Park S-J, Shin S-H, Hong G-R, Lee S, Kim M-S et al. Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation: PRIME Study. Circulation. 2019;139(11):1354–65. DOI: 10.1161/CIRCULATIONAHA.118.037077
75. Ovchinnikov AG, Dreeva ZV, Potekhina AV, Arefieva TI, Masenko VP, Ageev FT. Abstracts Programme. P1686. Statins improves functional capacity and restores LV diastolic reserve in patients with heart failure with preserved left ventricular ejection fraction. European Journal of Heart Failure. 2019;21(S1):418.. DOI: 10.1002/ejhf.1488
76. 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
77. Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E et al. How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). European Heart Journal. 2019;40(40):3297–317. DOI: 10.1093/eurheartj/ehz641
78. Madamanchi C, Alhosaini H, Sumida A, Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. International Journal of Cardiology. 2014;176(3):611–7. DOI: 10.1016/j.ijcard.2014.08.007
79. 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
80. Suematsu Y, Miura S, Goto M, Matsuo Y, Arimura T, Kuwano T et al. LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice: LCZ696 improves cardiac function. European Journal of Heart Failure. 2016;18(4):386–93. DOI: 10.1002/ejhf.474
81. Ovchinnikov AG, Arefieva TI, Potekhina AV, Filatova AYu, Ageev FT, Boytsov SА. The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction. Acta Naturae. 2020;12(2):40–51. DOI: 10.32607/actanaturae.10990
82. Zhang H, Liu G, Zhou W, Zhang W, Wang K, Zhang J. Neprilysin Inhibitor–Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice. Scientific Reports. 2019;9(1):6509. DOI: 10.1038/s41598-019-42994-1
83. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP et al. Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. New England Journal of Medicine. 2019;381(17):1609–20. DOI: 10.1056/NEJMoa1908655
84. McMurray JJV, Jackson AM, Lam CSP, Redfield MM, Anand IS, Ge J et al. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF. Circulation. 2020;141(5):338–51. DOI: 10.1161/CIRCULATIONAHA.119.044491
85. Solomon SD, Vaduganathan ML, Claggett BL, Packer M, Zile M, Swedberg K et al. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. Circulation. 2020;141(5):352–61. DOI: 10.1161/CIRCULATIONAHA.119.044586
86. Packer M, Kitzman DW. Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2. JACC: Heart Failure. 2018;6(8):633–9. DOI: 10.1016/j.jchf.2018.01.009
87. 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
88. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Target of Phosphodiesterase-5 Inhibition in a 1-Year Study. Circulation. 2011;124(2):164–74. DOI: 10.1161/CIRCULATIONAHA.110.983866
89. Belyavskiy E, Ovchinnikov A, Potekhina A, Ageev F, Edelmann F. Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study. BMC Cardiovascular Disorders. 2020;20(1):408. DOI: 10.1186/s12872-020-01671-2
90. Meems LMG, Burnett JC. Innovative Therapeutics: designer natriuretic peptides. JACC: Basic to Translational Science. 2016;1(7):557–67. DOI: 10.1016/j.jacbts.2016.10.001