Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Research Update on the Pathophysiological Mechanisms of Heart Failure with Preserved Ejection Fraction

Author(s): Yuying Zhou, Yunlong Zhu and Jianping Zeng*

Volume 23, Issue 1, 2023

Published on: 18 February, 2022

Page: [54 - 62] Pages: 9

DOI: 10.2174/1566524021666211129111202

open access plus

conference banner
Abstract

Heart failure (HF) is a serious clinical syndrome, usually occurs at the advanced stage of various cardiovascular diseases, featured by high mortality and rehospitalization rate. According to left ventricular (LV) ejection fraction (LVEF), HF has been categorized as HF with reduced EF (HFrEF; LVEF<40%), HF with mid-range EF (HFmrEF; LVEF 40-49%), and HF with preserved EF (HFpEF; LVEF ≥50%). HFpEF accounts for about 50% of cases of heart failure and has become the dominant form of heart failure. The mortality of HFpEF is similar to that of HFrEF. There are no welldocumented treatment options that can reduce the morbidity and mortality of HFpEF now. Understanding the underlying pathological mechanisms is essential for the development of novel effective therapy options for HFpEF. In recent years, significant research progress has been achieved on the pathophysiological mechanism of HFpEF. This review aimed to update the research progress on the pathophysiological mechanism of HFpEF.

Keywords: Heart failure, diastolic dysfunction, inflammation and oxidative stress, endothelial dysfunction, chronotropic incompetence, cardiac reserve dysfunction, pulmonary hypertension.

« Previous Next »
[1]
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC). Developed with the special contribution of the heart failure Association (HFA) of the ESC. Eur J Heart Fail 2016; 18(8): 891-975.
[http://dx.doi.org/10.1002/ejhf.592] [PMID: 27207191]
[2]
Ge J. Coding proposal on phenotyping heart failure with preserved ejection fraction: a practical tool for facilitating etiology-oriented therapy. Cardiol J 2020; 27(1): 97-8.
[http://dx.doi.org/10.5603/CJ.2020.0023] [PMID: 32103486]
[3]
van Heerebeek L, Franssen CP, Hamdani N, Verheugt FW, Somsen GA, Paulus WJ. Molecular and cellular basis for diastolic dysfunction. Curr Heart Fail Rep 2012; 9(4): 293-302.
[http://dx.doi.org/10.1007/s11897-012-0109-5] [PMID: 22926993]
[4]
Kemp CD, Conte JV. The pathophysiology of heart failure. Cardiovasc Pathol 2012; 21(5): 365-71.
[http://dx.doi.org/10.1016/j.carpath.2011.11.007] [PMID: 22227365]
[5]
Pieske B, Tschöpe C, de Boer RA, 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). Eur J Heart Fail 2020; 22(3): 391-412.
[http://dx.doi.org/10.1002/ejhf.1741] [PMID: 32133741]
[6]
Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2011; 32(6): 670-9.
[http://dx.doi.org/10.1093/eurheartj/ehq426] [PMID: 21138935]
[7]
Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 2014; 11(9): 507-15.
[http://dx.doi.org/10.1038/nrcardio.2014.83] [PMID: 24958077]
[8]
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 Fail Rev 2014; 19(5): 681-94.
[http://dx.doi.org/10.1007/s10741-013-9405-8] [PMID: 24005868]
[9]
Czuriga D, Czuriga A, Édes I, Papp Z, Borbély A. Cellular mechanisms for diastolic dysfunction in the human heart. Curr Pharm Biotechnol 2012; 13: 2532-8.
[http://dx.doi.org/10.2174/1389201011208062532]
[10]
Zhi H, Luptak I, Alreja G, et al. Effects of direct renin inhibition on myocardial fibrosis and cardiac fibroblast function. PLoS One 2013; 8: e81612.
[http://dx.doi.org/10.1371/journal.pone.0081612] [PMID: 24349097]
[11]
Tamaki S, Mano T, Sakata Y, et al. Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction. PLoS One 2013; 8(7): e68893.
[http://dx.doi.org/10.1371/journal.pone.0068893] [PMID: 23894370]
[12]
Su MY, Lin LY, Tseng YH, et al. CMR-verified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF. JACC Cardiovasc Imaging 2014; 7(10): 991-7.
[http://dx.doi.org/10.1016/j.jcmg.2014.04.022] [PMID: 25240451]
[13]
Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 2011; 57(8): 891-903.
[http://dx.doi.org/10.1016/j.jacc.2010.11.013] [PMID: 21329834]
[14]
Sweeney M, Corden B, Cook SA. Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle? EMBO Mol Med 2020; 12(10): e10865.
[http://dx.doi.org/10.15252/emmm.201910865] [PMID: 32955172]
[15]
Friebel J, Weithauser A, Witkowski M, et al. Protease-activated receptor 2 deficiency mediates cardiac fibrosis and diastolic dysfunction. Eur Heart J 2019; 40(40): 3318-32.
[http://dx.doi.org/10.1093/eurheartj/ehz117] [PMID: 31004144]
[16]
Rodriguez P, Sassi Y, Troncone L, et al. Deletion of delta-like 1 homologue accelerates fibroblast-myofibroblast differentiation and induces myocardial fibrosis. Eur Heart J 2019; 40(12): 967-78.
[http://dx.doi.org/10.1093/eurheartj/ehy188] [PMID: 29668883]
[17]
Snead AN, Insel PA. Defining the cellular repertoire of GPCRs identifies a profibrotic role for the most highly expressed receptor, protease-activated receptor 1, in cardiac fibroblasts. FASEB J 2012; 26(11): 4540-7.
[http://dx.doi.org/10.1096/fj.12-213496] [PMID: 22859370]
[18]
González A, López B, Querejeta R, Zubillaga E, Echeverría T, Díez J. Filling pressures and collagen metabolism in hypertensive patients with heart failure and normal ejection fraction. Hypertension 2010; 55(6): 1418-24.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.149112] [PMID: 20404218]
[19]
Massie BMCP, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359(23): 2456-67.
[http://dx.doi.org/10.1056/NEJMoa0805450] [PMID: 19001508]
[20]
Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83(6): 1849-65.
[http://dx.doi.org/10.1161/01.CIR.83.6.1849] [PMID: 1828192]
[21]
Kitzman DW, Upadhya B, Vasu S. What the dead can teach the living: systemic nature of heart failure with preserved ejection fraction. Circulation 2015; 131(6): 522-4.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.014420] [PMID: 25552355]
[22]
Borbély A, van der Velden J, Papp Z, et al. Cardiomyocyte stiffness in diastolic heart failure. Circulation 2005; 111(6): 774-81.
[http://dx.doi.org/10.1161/01.CIR.0000155257.33485.6D] [PMID: 15699264]
[23]
Paulus WJ, Tschöpe 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.
[http://dx.doi.org/10.1016/j.jacc.2013.02.092] [PMID: 23684677]
[24]
Røe ÅT, Aronsen JM, Skårdal K, et al. Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy. Cardiovasc Res 2017; 113(10): 1161-72.
[http://dx.doi.org/10.1093/cvr/cvx087] [PMID: 28472418]
[25]
Kho C, Lee A, Hajjar RJ. Altered sarcoplasmic reticulum calcium cycling-targets for heart failure therapy. Nat Rev Cardiol 2012; 9(12): 717-33.
[http://dx.doi.org/10.1038/nrcardio.2012.145] [PMID: 23090087]
[26]
Kawase Y, Hajjar RJ. The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: a potent target for cardiovascular diseases. Nat Clin Pract Cardiovasc Med 2008; 5(9): 554-65.
[http://dx.doi.org/10.1038/ncpcardio1301] [PMID: 18665137]
[27]
Gorski PA, Jang SP, Jeong D, et al. Role of SIRT1 in modulating acetylation of the sarco-endoplasmic reticulum Ca2+-ATPase in heart failure. Circ Res 2019; 124(9): e63-80.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313865] [PMID: 30786847]
[28]
Shah AM, Harold A, Spurgeon SJS, Talo A, Lakatta EG. 8-bromo-cGMP reduces the myofilament response to Ca21 in intact cardiac myocytes. Circ Res 1994; 74(5): 970-8.
[http://dx.doi.org/10.1161/01.RES.74.5.970] [PMID: 8156644]
[29]
Vila-Petroff MG, Younes A, Egan J, Lakatta EG, Sollott SJ. Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes. Circ Res 1999; 84(9): 1020-31.
[http://dx.doi.org/10.1161/01.RES.84.9.1020] [PMID: 10325239]
[30]
Zieman SJ, Gerstenblith G, Lakatta EG, et al. Upregulation of the nitric oxide-cGMP pathway in aged myocardium: physiological response to l-arginine. Circ Res 2001; 88(1): 97-102.
[http://dx.doi.org/10.1161/01.RES.88.1.97] [PMID: 11139480]
[31]
Han X, Wang Y, Fu M, et al. Effects of adiponectin on diastolic function in mice underwent transverse aorta constriction. J Cardiovasc Transl Res 2020; 13(2): 225-37.
[http://dx.doi.org/10.1007/s12265-019-09913-1] [PMID: 31621035]
[32]
Diwan A, Tran T, Misra A, Mann DL. Inflammatory mediators and the failing heart A translational approach. Curr Mol Med 2003; 3(2): 161-82.
[http://dx.doi.org/10.2174/1566524033361537]
[33]
Michels da Silva D, Langer H, Graf T. Inflammatory and molecular pathways in heart failure-ischemia, HFpEF and transthyretin cardiac amyloidosis. Int J Mol Sci 2019; 20(9): 2322.
[http://dx.doi.org/10.3390/ijms20092322] [PMID: 31083399]
[34]
Zhazykbayeva S, Pabel S, Mügge A, Sossalla S, Hamdani N. The molecular mechanisms associated with the physiological responses to inflammation and oxidative stress in cardiovascular diseases. Biophys Rev 2020; 12(4): 947-68.
[http://dx.doi.org/10.1007/s12551-020-00742-0] [PMID: 32691301]
[35]
Altara R, Giordano M, Nordén ES, et al. Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Front Endocrinol (Lausanne) 2017; 8: 160.
[http://dx.doi.org/10.3389/fendo.2017.00160] [PMID: 28769873]
[36]
Gevaert AB, Shakeri H, Leloup AJ, et al. Endothelial senescence contributes to heart failure with preserved ejection fraction in an aging mouse model. Circ Heart Fail 2017; 10(6): e003806.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.116.003806] [PMID: 28611124]
[37]
Paulus WJ, Dal Canto E. Distinct myocardial targets for diabetes therapy in heart failure with preserved or reduced ejection fraction. JACC Heart Fail 2018; 6(1): 1-7.
[http://dx.doi.org/10.1016/j.jchf.2017.07.012] [PMID: 29284577]
[38]
Brandt MM, Nguyen ITN, Krebber MM, et al. Limited synergy of obesity and hypertension, prevalent risk factors in onset and progression of heart failure with preserved ejection fraction. J Cell Mol Med 2019; 23(10): 6666-78.
[http://dx.doi.org/10.1111/jcmm.14542] [PMID: 31368189]
[39]
Waddingham MT, Sonobe T, Tsuchimochi H, et al. Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model. J Mol Cell Cardiol 2019; 137: 119-31.
[http://dx.doi.org/10.1016/j.yjmcc.2019.10.005] [PMID: 31669609]
[40]
Yamamoto E, Hirata Y, Tokitsu T, et al. The pivotal role of eNOS uncoupling in vascular endothelial dysfunction in patients with heart failure with preserved ejection fraction. Int J Cardiol 2015; 190: 335-7.
[http://dx.doi.org/10.1016/j.ijcard.2015.04.162] [PMID: 25935623]
[41]
Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG. “Pure” diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 2005; 7(5): 820-8.
[http://dx.doi.org/10.1016/j.ejheart.2005.02.003] [PMID: 15921957]
[42]
Cioffi G, Senni M, Tarantini L, et al. Analysis of circumferential and longitudinal left ventricular systolic function in patients with non-ischemic chronic heart failure and preserved ejection fraction (from the CARRY-IN-HFpEF study). Am J Cardiol 2012; 109(3): 383-9.
[http://dx.doi.org/10.1016/j.amjcard.2011.09.022] [PMID: 22112740]
[43]
Ballo P, Quatrini I, Giacomin E, Motto A, Mondillo S. Circumferential versus longitudinal systolic function in patients with hypertension: a nonlinear relation. J Am Soc Echocardiogr 2007; 20(3): 298-306.
[http://dx.doi.org/10.1016/j.echo.2006.08.024] [PMID: 17336758]
[44]
Carluccio E, Biagioli P, Alunni G, et al. Advantages of deformation indices over systolic velocities in assessment of longitudinal systolic function in patients with heart failure and normal ejection fraction. Eur J Heart Fail 2011; 13(3): 292-302.
[http://dx.doi.org/10.1093/eurjhf/hfq203] [PMID: 21112882]
[45]
Hu K, Liu D, Herrmann S, et al. Clinical implication of mitral annular plane systolic excursion for patients with cardiovascular disease. Eur Heart J Cardiovasc Imaging 2013; 14(3): 205-12.
[http://dx.doi.org/10.1093/ehjci/jes240] [PMID: 23161791]
[46]
DeVore AD, McNulty S, Alenezi F, et al. Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial. Eur J Heart Fail 2017; 19(7): 893-900.
[http://dx.doi.org/10.1002/ejhf.754] [PMID: 28194841]
[47]
Mohammed SF, Borlaug BA, McNulty S, et al. Resting ventricular-vascular function and exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail 2014; 7: 580-9.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.001192] [PMID: 24833648]
[48]
Phan TT, Shivu GN, Abozguia K, et al. Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3(1): 29-34.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.109.877720] [PMID: 19917649]
[49]
Sarma S, Stoller D, Hendrix J, et al. Mechanisms of Chronotropic Incompetence in heart failure with preserved ejection fraction. Circ Heart Fail 2020; 13(3): e006331.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006331] [PMID: 32164435]
[50]
Katoh S, Shishido T, Kutsuzawa D, et al. Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction. Ann Nucl Med 2010; 24(9): 679-86.
[http://dx.doi.org/10.1007/s12149-010-0409-3] [PMID: 20824398]
[51]
Sarma S, Howden E, Lawley J, Samels M, Levine BD. Central command and the regulation of exercise heart rate response in heart failure with preserved ejection fraction. Circulation 2021; 143(8): 783-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048338] [PMID: 33205661]
[52]
Hoeper MM, Lam CSP, Vachiery JL, et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a plea for proper phenotyping and further research. Eur Heart J 2017; 38(38): 2869-73.
[http://dx.doi.org/10.1093/eurheartj/ehw597] [PMID: 28011705]
[53]
Waxman AB. Pulmonary hypertension in heart failure with preserved ejection fraction: a target for therapy? Circulation 2011; 124(2): 133-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.038885] [PMID: 21747065]
[54]
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.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.983866] [PMID: 21709061]
[55]
Yin J, Kukucka M, Hoffmann J, et al. Sildenafil preserves lung endothelial function and prevents pulmonary vascular remodeling in a rat model of diastolic heart failure. Circ Heart Fail 2011; 4(2): 198-206.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.110.957050] [PMID: 21216837]
[56]
Ohara T, Ohte N, Little WC. Pulmonary hypertension in heart failure with preserved left ventricular ejection fraction: diagnosis and management. Curr Opin Cardiol 2012; 27(3): 281-7.
[http://dx.doi.org/10.1097/HCO.0b013e32835220b1] [PMID: 22450719]
[57]
Santas E, Palau P, Guazzi M, et al. Usefulness of Right Ventricular to pulmonary circulation coupling as an indicator of risk for recurrent admissions in heart failure with preserved ejection fraction. Am J Cardiol 2019; 124(4): 567-72.
[http://dx.doi.org/10.1016/j.amjcard.2019.05.024] [PMID: 31204033]
[58]
Thenappan T, Shah SJ, Gomberg-Maitland M, et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail 2011; 4(3): 257-65.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.110.958801] [PMID: 21411741]
[59]
Gerges M, Gerges C, Pistritto A-M, et al. Pulmonary hypertension in heart failure: Epidemiology, right ventricular function and survival. Am J Respir Crit Care Med 2015; 192: 1234-46.
[60]
Shults NV, Kanovka SS, Ten Eyck JE, Rybka V, Suzuki YJ. Ultrastructural changes of the right ventricular myocytes in pulmonary arterial hypertension. J Am Heart Assoc 2019; 8(5): e011227.
[http://dx.doi.org/10.1161/JAHA.118.011227] [PMID: 30807241]
[61]
Potus F, Ruffenach G, Dahou A, et al. Downregulation of MicroRNA-126 contributes to the failing right ventricle in pulmonary arterial hypertension. Circulation 2015; 132(10): 932-43.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016382] [PMID: 26162916]
[62]
Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 2003; 107(5): 714-20.
[http://dx.doi.org/10.1161/01.CIR.0000048123.22359.A0] [PMID: 12578874]
[63]
Ikonomidis I, Aboyans V, Blacher J, et al. The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European society of cardiology working group on aorta & peripheral vascular diseases, European association of cardiovascular imaging, and heart failure association. Eur J Heart Fail 2019; 21(4): 402-24.
[http://dx.doi.org/10.1002/ejhf.1436] [PMID: 30859669]
[64]
Sotomi Y, Iwakura K, Hikoso S, et al. Prognostic significance of the HFA-PEFF score in patients with heart failure with preserved ejection fraction. ESC Heart Fail 2021; 8(3): 2154-64.
[http://dx.doi.org/10.1002/ehf2.13302] [PMID: 33760383]
[65]
Suzuki S, Kaikita K, Yamamoto E, et al. H2FPEF score for predicting future heart failure in stable outpatients with cardiovascular risk factors. ESC Heart Fail 2020; 7: 66-75.
[http://dx.doi.org/10.1002/ehf2.12570]
[66]
McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42(36): 3599-726.
[http://dx.doi.org/10.1093/eurheartj/ehab368] [PMID: 34447992]
[67]
Barandiarán Aizpurua A, Sanders-van Wijk S, Brunner-La Rocca HP, et al. Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction. Eur J Heart Fail 2020; 22(3): 413-21.
[http://dx.doi.org/10.1002/ejhf.1614] [PMID: 31472035]
[68]
Pieske B, Tschöpe C, de Boer RA, 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). Eur Heart J 2019; 40(40): 3297-317.
[http://dx.doi.org/10.1093/eurheartj/ehz641] [PMID: 31504452]
[69]
Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation 2018; 138(9): 861-70.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034646] [PMID: 29792299]
[70]
Anker SD, Butler J, Filippatos G, et al. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial. Eur J Heart Fail 2020; 22(12): 2383-92.
[http://dx.doi.org/10.1002/ejhf.2064] [PMID: 33251670]
[71]
Packer M. Mechanisms leading to differential hypoxia-inducible factor signaling in the diabetic kidney: modulation by SGLT2 inhibitors and hypoxia mimetics. Am J Kidney Dis 2021; 77(2): 280-6.
[http://dx.doi.org/10.1053/j.ajkd.2020.04.016] [PMID: 32711072]
[72]
Chairat K, Rattanavipanon W, Tanyasaensook K, Chindavijak B, Chulavatnatol S, Nathisuwan S. Relationship of anemia and clinical outcome in heart failure patients with preserved versus reduced ejection fraction in a rural area of Thailand. Int J Cardiol Heart Vasc 2020; 30: 100597.
[http://dx.doi.org/10.1016/j.ijcha.2020.100597] [PMID: 32775603]
[73]
Zeng J, Zhu Y, Zhao W, et al. Rationale and design of the Adidas study: association between dapagliflozin-induced improvement and anemia in heart failure patients. Cardiovasc Drugs Ther 2021. Online Ahead of Print.
[http://dx.doi.org/10.1007/s10557-021-07176-0] [PMID: 33779938]

Rights & Permissions Print Cite
Article Metrics
94
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy