1932

Abstract

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome.

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2022-01-27
2024-06-14
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Literature Cited

  1. 1. 
    Virani SS, Alonso A, Benjamin EJ et al. 2020. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation 141:e139–e596
    [Google Scholar]
  2. 2. 
    Owan TE, Hodge DO, Herges RM et al. 2006. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N. Engl. J. Med. 355:251–59
    [Google Scholar]
  3. 3. 
    Shah SJ, Borlaug BA, Kitzman DW et al. 2020. Research priorities for heart failure with preserved ejection fraction: National Heart, Lung, and Blood Institute Working Group summary. Circulation 141:1001–26
    [Google Scholar]
  4. 4. 
    Tsao CW, Lyass A, Enserro D et al. 2018. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail 6:678–85
    [Google Scholar]
  5. 5. 
    Reddy YNV, Rikhi A, Obokata M et al. 2020. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur. J. Heart Fail. 22:1009–18
    [Google Scholar]
  6. 6. 
    Shah KS, Xu H, Matsouaka RA et al. 2017. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J. Am. Coll. Cardiol. 70:2476–86
    [Google Scholar]
  7. 7. 
    Borlaug BA. 2020. Evaluation and management of heart failure with preserved ejection fraction. Nat. Rev. Cardiol. 17:559–73
    [Google Scholar]
  8. 8. 
    Pfeffer MA, Shah AM, Borlaug BA. 2019. Heart failure with preserved ejection fraction in perspective. Circ. Res. 124:1598–617
    [Google Scholar]
  9. 9. 
    Borlaug BA. 2014. The pathophysiology of heart failure with preserved ejection fraction. Nat. Rev. Cardiol. 11:507–15
    [Google Scholar]
  10. 10. 
    Mishra S, Kass DA 2021. Cellular and molecular pathobiology of heart failure with preserved ejection fraction. Nat. Rev. Cardiol. 18:400–23
    [Google Scholar]
  11. 11. 
    Obokata M, Olson TP, Reddy YNV et al. 2018. Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction. Eur. Heart J. 39:2810–21
    [Google Scholar]
  12. 12. 
    Reddy YNV, Borlaug BA. 2021. Pulmonary hypertension in left heart disease. Clin. Chest Med. 42:39–58
    [Google Scholar]
  13. 13. 
    Reddy YNV, Obokata M, Wiley B et al. 2019. The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction. Eur. Heart J. 40:3721–30
    [Google Scholar]
  14. 14. 
    Bers DM. 2008. Calcium cycling and signaling in cardiac myocytes. Annu. Rev. Physiol. 70:23–49
    [Google Scholar]
  15. 15. 
    Selby DE, Palmer BM, LeWinter MM et al. 2011. Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction. J. Am. Coll. Cardiol. 58:147–54
    [Google Scholar]
  16. 16. 
    Frisk M, Le C, Shen X et al. 2021. Etiology-dependent impairment of diastolic cardiomyocyte calcium homeostasis in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 77:405–19
    [Google Scholar]
  17. 17. 
    Kilfoil PJ, Lotteau S, Zhang R et al. 2020. Distinct features of calcium handling and β-adrenergic sensitivity in heart failure with preserved versus reduced ejection fraction. J. Physiol. 598:5091–108
    [Google Scholar]
  18. 18. 
    Reddy YNV, Andersen MJ, Obokata M et al. 2017. Arterial stiffening with exercise in patients with heart failure and preserved ejection fraction. J. Am. Coll. Cardiol. 70:136–48
    [Google Scholar]
  19. 19. 
    Weber T, Chirinos JA. 2018. Pulsatile arterial haemodynamics in heart failure. Eur. Heart J. 39:3847–54
    [Google Scholar]
  20. 20. 
    Hay I, Rich J, Ferber P et al. 2005. Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure. Am. J. Physiol. Heart Circ. Physiol. 288:H1203–8
    [Google Scholar]
  21. 21. 
    Borlaug BA, Jaber WA, Ommen SR et al. 2011. Diastolic relaxation and compliance reserve during dynamic exercise in heart failure with preserved ejection fraction. Heart 97:964–69
    [Google Scholar]
  22. 22. 
    Zile MR, Baicu CF, Gaasch WH. 2004. Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle. N. Engl. J. Med. 350:1953–59
    [Google Scholar]
  23. 23. 
    Methawasin M, Strom JG, Slater RE et al. 2016. Experimentally increasing the compliance of titin through RNA binding motif-20 (RBM20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction. Circulation 134:1085–99
    [Google Scholar]
  24. 24. 
    van Heerebeek L, Hamdani N, Falcão-Pires I et al. 2012. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 126:830–39
    [Google Scholar]
  25. 25. 
    Zile MR, Baicu CF, Ikonomidis JS et al. 2015. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation 131:1247–59
    [Google Scholar]
  26. 26. 
    Ng ACT, Delgado V, Borlaug BA et al. 2021. Diabesity: the combined burden of obesity and diabetes on heart disease and the role of imaging. Nat. Rev. Cardiol. 18:291–304
    [Google Scholar]
  27. 27. 
    Rommel KP, von Roeder M, Latuscynski K et al. 2016. Extracellular volume fraction for characterization of patients with heart failure and preserved ejection fraction. J. Am. Coll. Cardiol. 67:1815–25
    [Google Scholar]
  28. 28. 
    Borlaug BA, Lam CS, Roger VL et al. 2009. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 54:410–18
    [Google Scholar]
  29. 29. 
    Kraigher-Krainer E, Shah AM, Gupta DK et al. 2014. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 63:447–56
    [Google Scholar]
  30. 30. 
    Tan YT, Wenzelburger F, Lee E et al. 2009. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J. Am. Coll. Cardiol. 54:36–46
    [Google Scholar]
  31. 31. 
    Shah AM, Claggett B, Sweitzer NK et al. 2015. Prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone. Circulation 132:402–14
    [Google Scholar]
  32. 32. 
    Sorimachi H, Burkhoff D, Verbrugge FH et al. 2021. Obesity, venous capacitance, and venous compliance in heart failure with preserved ejection fraction. Eur. J. Heart Fail 23:164858
    [Google Scholar]
  33. 33. 
    Borlaug BA, Kane GC, Melenovsky V et al. 2016. Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur. Heart J. 37:3293–302
    [Google Scholar]
  34. 34. 
    Borlaug BA, Olson TP, Lam CS et al. 2010. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 56:845–54
    [Google Scholar]
  35. 35. 
    Phan TT, Abozguia K, Nallur Shivu G et al. 2009. Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J. Am. Coll. Cardiol. 54:402–9
    [Google Scholar]
  36. 36. 
    Backhaus SJ, Lange T, George EF et al. 2021. Exercise stress real-time cardiac magnetic resonance imaging for noninvasive characterization of heart failure with preserved ejection fraction: the HFpEF-Stress Trial. Circulation 143:1484–98
    [Google Scholar]
  37. 37. 
    Melenovsky V, Borlaug BA, Rosen B et al. 2007. Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction. J. Am. Coll. Cardiol. 49:198–207
    [Google Scholar]
  38. 38. 
    Melenovsky V, Hwang SJ, Redfield MM et al. 2015. Left atrial remodeling and function in advanced heart failure with preserved or reduced ejection fraction. Circ. Heart Fail. 8:295–303
    [Google Scholar]
  39. 39. 
    Reddy YNV, Obokata M, Egbe A et al. 2019. Left atrial strain and compliance in the diagnostic evaluation of heart failure with preserved ejection fraction. Eur. J. Heart Fail. 21:891–900
    [Google Scholar]
  40. 40. 
    Triposkiadis F, Pieske B, Butler J et al. 2016. Global left atrial failure in heart failure. Eur. J. Heart Fail. 18:1307–20
    [Google Scholar]
  41. 41. 
    Freed BH, Daruwalla V, Cheng JY et al. 2016. Prognostic utility and clinical significance of cardiac mechanics in heart failure with preserved ejection fraction: importance of left atrial strain. Circ. Cardiovasc. Imaging 9:e003754
    [Google Scholar]
  42. 42. 
    Santos AB, Roca GQ, Claggett B et al. 2016. Prognostic relevance of left atrial dysfunction in heart failure with preserved ejection fraction. Circ. Heart Fail. 9:e002763
    [Google Scholar]
  43. 43. 
    Telles F, Nanayakkara S, Evans S et al. 2019. Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 21:495–505
    [Google Scholar]
  44. 44. 
    Reddy YNV, Obokata M, Verbrugge FH et al. 2020. Atrial dysfunction in patients with heart failure with preserved ejection fraction and atrial fibrillation. J. Am. Coll. Cardiol. 76:1051–64
    [Google Scholar]
  45. 45. 
    Verbrugge FH, Guazzi M, Testani JM et al. 2020. Altered hemodynamics and end-organ damage in heart failure: impact on the lung and kidney. Circulation 142:998–1012
    [Google Scholar]
  46. 46. 
    Phan TT, Abozguia K, Shivu GN et al. 2009. Increased atrial contribution to left ventricular filling compensates for impaired early filling during exercise in heart failure with preserved ejection fraction. J. Card. Fail. 15:890–7
    [Google Scholar]
  47. 47. 
    Tamargo M, Obokata M, Reddy YNV et al. 2020. Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 22:489–98
    [Google Scholar]
  48. 48. 
    Borlaug BA, Reddy YNV. 2019. The role of the pericardium in heart failure: implications for pathophysiology and treatment. JACC Heart Fail 7:574–85
    [Google Scholar]
  49. 49. 
    Lam CS, Rienstra M, Tay WT et al. 2017. Atrial fibrillation in heart failure with preserved ejection fraction: association with exercise capacity, left ventricular filling pressures, natriuretic peptides, and left atrial volume. JACC Heart Fail 5:92–98
    [Google Scholar]
  50. 50. 
    Obokata M, Reddy YNV, Melenovsky V et al. 2019. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction. Eur. Heart J. 40:689–97
    [Google Scholar]
  51. 51. 
    Zakeri R, Chamberlain AM, Roger VL et al. 2013. Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study. Circulation 128:1085–93
    [Google Scholar]
  52. 52. 
    Guazzi M, Naeije R. 2017. Pulmonary hypertension in heart failure: pathophysiology, pathobiology, and emerging clinical perspectives. J. Am. Coll. Cardiol. 69:1718–34
    [Google Scholar]
  53. 53. 
    Gorter TM, Obokata M, Reddy YNV et al. 2018. Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease. Eur. Heart J. 39:2825–35
    [Google Scholar]
  54. 54. 
    Lai YC, Wang L, Gladwin MT. 2019. Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction. J. Physiol. 597:1143–56
    [Google Scholar]
  55. 55. 
    Vanderpool RR, Saul M, Nouraie M et al. 2018. Association between hemodynamic markers of pulmonary hypertension and outcomes in heart failure with preserved ejection fraction. JAMA Cardiol 3:298–306
    [Google Scholar]
  56. 56. 
    Fayyaz AU, Edwards WD, Maleszewski JJ et al. 2018. Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction. Circulation 137:1796–810
    [Google Scholar]
  57. 57. 
    Gorter TM, Hoendermis ES, van Veldhuisen DJ et al. 2016. Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Eur. J. Heart Fail. 18:1472–87
    [Google Scholar]
  58. 58. 
    Melenovsky V, Hwang SJ, Lin G et al. 2014. Right heart dysfunction in heart failure with preserved ejection fraction. Eur. Heart J. 35:3452–62
    [Google Scholar]
  59. 59. 
    Olson TP, Johnson BD, Borlaug BA. 2016. Impaired pulmonary diffusion in heart failure with preserved ejection fraction. JACC Heart Fail 4:490–98
    [Google Scholar]
  60. 60. 
    Fermoyle CC, Stewart GM, Borlaug BA et al. 2021. Simultaneous measurement of lung diffusing capacity and pulmonary hemodynamics reveals exertional alveolar-capillary dysfunction in heart failure with preserved ejection fraction. J. Am. Heart Assoc. 10:16e019950
    [Google Scholar]
  61. 61. 
    Hoeper MM, Meyer K, Rademacher J et al. 2016. Diffusion capacity and mortality in patients with pulmonary hypertension due to heart failure with preserved ejection fraction. JACC Heart Fail 4:441–49
    [Google Scholar]
  62. 62. 
    Chirinos JA, Bhattacharya P, Kumar A et al. 2019. Impact of diabetes mellitus on ventricular structure, arterial stiffness, and pulsatile hemodynamics in heart failure with preserved ejection fraction. J. Am. Heart Assoc. 8:e011457
    [Google Scholar]
  63. 63. 
    Kawaguchi M, Hay I, Fetics B et al. 2003. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation 107:714–20
    [Google Scholar]
  64. 64. 
    Schwartzenberg S, Redfield MM, From AM et al. 2012. Effects of vasodilation in heart failure with preserved or reduced ejection fraction: implications of distinct pathophysiologies on response to therapy. J. Am. Coll. Cardiol. 59:442–51
    [Google Scholar]
  65. 65. 
    Akiyama E, Sugiyama S, Matsuzawa Y et al. 2012. Incremental prognostic significance of peripheral endothelial dysfunction in patients with heart failure with normal left ventricular ejection fraction. J. Am. Coll. Cardiol. 60:1778–86
    [Google Scholar]
  66. 66. 
    Paulus WJ, Tschöpe C. 2013. 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. 62:263–71
    [Google Scholar]
  67. 67. 
    Sanders-van Wijk S, Tromp J, Beussink-Nelson L et al. 2020. Proteomic evaluation of the comorbidity-inflammation paradigm in heart failure with preserved ejection fraction: results from the PROMIS-HFpEF study. Circulation 142:2029–44
    [Google Scholar]
  68. 68. 
    Ahmad A, Corban MT, Toya T et al. 2020. Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction. Eur. J. Heart Fail. https://doi.org/10.1002/ejhf.2010
    [Crossref] [Google Scholar]
  69. 69. 
    Shah SJ, Lam CSP, Svedlund S et al. 2018. Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF. Eur. Heart J. 39:3439–50
    [Google Scholar]
  70. 70. 
    Yang JH, Obokata M, Reddy YNV et al. 2020. Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction. Eur. J. Heart Fail. 22:432–41
    [Google Scholar]
  71. 71. 
    Obokata M, Reddy YNV, Melenovsky V et al. 2018. Myocardial injury and cardiac reserve in patients with heart failure and preserved ejection fraction. J. Am. Coll. Cardiol. 72:29–40
    [Google Scholar]
  72. 72. 
    Abudiab MM, Redfield MM, Melenovsky V et al. 2013. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 15:776–85
    [Google Scholar]
  73. 73. 
    Borlaug BA, Melenovsky V, Russell SD et al. 2006. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 114:2138–47
    [Google Scholar]
  74. 74. 
    Sarma S, Stoller D, Hendrix J et al. 2020. Mechanisms of chronotropic incompetence in heart failure with preserved ejection fraction. Circ. Heart Fail. 13:e006331
    [Google Scholar]
  75. 75. 
    Sarma S, Howden E, Lawley J et al. 2021. Central command and the regulation of exercise heart rate response in heart failure with preserved ejection fraction. Circulation 143:783–89
    [Google Scholar]
  76. 76. 
    Funakoshi K, Hosokawa K, Kishi T et al. 2014. Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function. J. Card. Fail. 20:53–59
    [Google Scholar]
  77. 77. 
    Fudim M, Sobotka PA, Dunlap ME. 2021. Extracardiac abnormalities of preload reserve: mechanisms underlying exercise limitation in heart failure with preserved ejection fraction, autonomic dysfunction, and liver disease. Circ. Heart Fail. 14:e007308
    [Google Scholar]
  78. 78. 
    Bhella PS, Prasad A, Heinicke K et al. 2011. Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 13:1296–304
    [Google Scholar]
  79. 79. 
    Dhakal BP, Malhotra R, Murphy RM et al. 2015. Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction. Circ. Heart Fail. 8:286–94
    [Google Scholar]
  80. 80. 
    Haykowsky MJ, Brubaker PH, John JM et al. 2011. Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J. Am. Coll. Cardiol. 58:265–74
    [Google Scholar]
  81. 81. 
    Houstis NE, Eisman AS, Pappagianopoulos PP et al. 2018. Exercise intolerance in heart failure with preserved ejection fraction: diagnosing and ranking its causes using personalized O2 pathway analysis. Circulation 137:148–61
    [Google Scholar]
  82. 82. 
    Kitzman DW, Nicklas B, Kraus WE et al. 2014. Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction. Am. J. Physiol. Heart Circ. Physiol. 306:H1364–70
    [Google Scholar]
  83. 83. 
    Kumar AA, Kelly DP, Chirinos JA. 2019. Mitochondrial dysfunction in heart failure with preserved ejection fraction. Circulation 139:1435–50
    [Google Scholar]
  84. 84. 
    Molina AJ, Bharadwaj MS, Van Horn C et al. 2016. Skeletal muscle mitochondrial content, oxidative capacity, and Mfn2 expression are reduced in older patients with heart failure and preserved ejection fraction and are related to exercise intolerance. JACC Heart Fail 4:636–45
    [Google Scholar]
  85. 85. 
    Koepp KE, Obokata M, Reddy YNV et al. 2020. Hemodynamic and functional impact of epicardial adipose tissue in heart failure with preserved ejection fraction. JACC Heart Fail 8:657–66
    [Google Scholar]
  86. 86. 
    Obokata M, Reddy YNV, Pislaru SV et al. 2017. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 136:6–19
    [Google Scholar]
  87. 87. 
    Packer M, Lam CSP, Lund LH et al. 2020. Characterization of the inflammatory-metabolic phenotype of heart failure with a preserved ejection fraction: a hypothesis to explain influence of sex on the evolution and potential treatment of the disease. Eur. J. Heart Fail. 22:1551–67
    [Google Scholar]
  88. 88. 
    Rao VN, Zhao D, Allison MA et al. 2018. Adiposity and incident heart failure and its subtypes: MESA (Multi-Ethnic Study of Atherosclerosis). JACC Heart Fail 6:999–1007
    [Google Scholar]
  89. 89. 
    Sorimachi H, Obokata M, Takahashi N et al. 2021. Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction. Eur. Heart J. 42:1595–605
    [Google Scholar]
  90. 90. 
    Kitzman DW, Brubaker P, Morgan T et al. 2016. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 315:36–46
    [Google Scholar]
  91. 91. 
    Pandey A, Parashar A, Kumbhani D et al. 2015. Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials. Circ. Heart Fail. 8:33–40
    [Google Scholar]
  92. 92. 
    Mueller S, Winzer EB, Duvinage A et al. 2021. Effect of high-intensity interval training, moderate continuous training, or guideline-based physical activity advice on peak oxygen consumption in patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 325:542–51
    [Google Scholar]
  93. 93. 
    Hwang SJ, Melenovsky V, Borlaug BA. 2014. Implications of coronary artery disease in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 63:2817–27
    [Google Scholar]
  94. 94. 
    Packer DL, Piccini JP, Monahan KH et al. 2021. Ablation versus drug therapy for atrial fibrillation in heart failure: results from the CABANA trial. Circulation 143:1377–90
    [Google Scholar]
  95. 95. 
    Sugumar H, Nanayakkara S, Vizi D et al. 2021. A prospective STudy using invAsive haemodynamic measurements foLLowing catheter ablation for AF and early HFpEF: STALL AF-HFpEF. Eur. J. Heart Fail 23:78596
    [Google Scholar]
  96. 96. 
    Adamson PB, Abraham WT, Bourge RC et al. 2014. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ. Heart Fail. 7:935–44
    [Google Scholar]
  97. 97. 
    Abraham WT, Adamson PB, Bourge RC et al. 2011. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet 377:658–66
    [Google Scholar]
  98. 98. 
    Pitt B, Pfeffer MA, Assmann SF et al. 2014. Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med. 370:1383–92
    [Google Scholar]
  99. 99. 
    Pfeffer MA, Claggett B, Assmann SF et al. 2015. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 131:34–42
    [Google Scholar]
  100. 100. 
    Yancy CW, Jessup M, Bozkurt B et al. 2017. ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 136:e137–e161
    [Google Scholar]
  101. 101. 
    Solomon SD, McMurray JJV, Anand IS et al. 2019. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N. Engl. J. Med. 381:1609–20
    [Google Scholar]
  102. 102. 
    McMurray JJV, Jackson AM, Lam CSP et al. 2020. Effects of sacubitril-valsartan versus valsartan in women compared with men with heart failure and preserved ejection fraction: insights from PARAGON-HF. Circulation 141:338–51
    [Google Scholar]
  103. 103. 
    Solomon SD, Vaduganathan M, Claggett BL et al. 2020. Sacubitril/valsartan across the spectrum of ejection fraction in heart failure. Circulation 141:352–61
    [Google Scholar]
  104. 104. 
    Vaduganathan M, Claggett BL, Desai AS et al. 2020. Prior heart failure hospitalization, clinical outcomes, and response to sacubitril/valsartan compared with valsartan in HFpEF. J. Am. Coll. Cardiol. 75:245–54
    [Google Scholar]
  105. 105. 
    Cleland JGF, Bunting KV, Flather MD et al. 2018. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. Eur. Heart J. 39:26–35
    [Google Scholar]
  106. 106. 
    Silverman DN, Plante TB, Infeld M et al. 2019. Association of β-blocker use with heart failure hospitalizations and cardiovascular disease mortality among patients with heart failure with a preserved ejection fraction: a secondary analysis of the TOPCAT trial. JAMA Netw. Open. 2:e1916598
    [Google Scholar]
  107. 107. 
    Bhatt DL, Szarek M, Steg PG et al. 2021. Sotagliflozin in patients with diabetes and recent worsening heart failure. N. Engl. J. Med. 384:117–28
    [Google Scholar]
  108. 108. 
    Alehagen U, Benson L, Edner M et al. 2015. Association between use of statins and mortality in patients with heart failure and ejection fraction of ≥50. Circ. Heart Fail. 8:862–70
    [Google Scholar]
  109. 109. 
    Redfield MM, Chen HH, Borlaug BA et al. 2013. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 309:1268–77
    [Google Scholar]
  110. 110. 
    Redfield MM, Anstrom KJ, Levine JA et al. 2015. Isosorbide mononitrate in heart failure with preserved ejection fraction. N. Engl. J. Med. 373:2314–24
    [Google Scholar]
  111. 111. 
    Borlaug BA, Anstrom KJ, Lewis GD et al. 2018. Effect of inorganic nitrite versus placebo on exercise capacity among patients with heart failure with preserved ejection fraction: the INDIE-HFpEF randomized clinical trial. JAMA 320:1764–73
    [Google Scholar]
  112. 112. 
    Armstrong PW, Lam CSP, Anstrom KJ et al. 2020. Effect of vericiguat versus placebo on quality of life in patients with heart failure and preserved ejection fraction: the VITALITY-HFpEF randomized clinical trial. JAMA 324:1512–21
    [Google Scholar]
  113. 113. 
    Udelson JE, Lewis GD, Shah SJ et al. 2020. Effect of praliciguat on peak rate of oxygen consumption in patients with heart failure with preserved ejection fraction: the CAPACITY HFpEF randomized clinical trial. JAMA 324:1522–31
    [Google Scholar]
  114. 114. 
    Reddy YNV, Anantha-Narayanan M, Obokata M et al. 2019. Hemodynamic effects of weight loss in obesity: a systematic review and meta-analysis. JACC Heart Fail 7:678–87
    [Google Scholar]
  115. 115. 
    Feldman T, Mauri L, Kahwash R et al. 2018. Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): a phase 2, randomized, sham-controlled trial. Circulation 137:364–75
    [Google Scholar]
  116. 116. 
    Hasenfuß G, Hayward C, Burkhoff D et al. 2016. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet 387:1298–304
    [Google Scholar]
  117. 117. 
    Kaye DM, Hasenfuß G, Neuzil P et al. 2016. One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction. Circ. Heart Fail. 9:e003662
    [Google Scholar]
  118. 118. 
    Shah SJ, Feldman T, Ricciardi MJ et al. 2018. One-year safety and clinical outcomes of a transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction in the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (REDUCE LAP-HF I) trial: a randomized clinical trial. JAMA Cardiol 3:968–77
    [Google Scholar]
  119. 119. 
    Obokata M, Reddy YNV, Shah SJ et al. 2019. Effects of interatrial shunt on pulmonary vascular function in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 74:2539–50
    [Google Scholar]
  120. 120. 
    Borlaug BA, Carter RE, Melenovsky V et al. 2017. Percutaneous pericardial resection: a novel potential treatment for heart failure with preserved ejection fraction. Circ. Heart Fail. 10:e003612
    [Google Scholar]
  121. 121. 
    Borlaug BA, Schaff HV, Pochettino A et al. 2018. Pericardiotomy enhances left ventricular diastolic reserve with volume loading in humans. Circulation 138:2295–97
    [Google Scholar]
  122. 122. 
    Fudim M, Patel MR, Boortz-Marx R et al. 2021. Splanchnic nerve block mediated changes in stressed blood volume in heart failure. JACC Heart Fail 9:293–300
    [Google Scholar]
  123. 123. 
    Burkhoff D, Borlaug BA, Shah SJ et al. 2021. Levosimendan improves hemodynamics and exercise tolerance in PH-HFpEF: results of the randomized placebo-controlled HELP trial. JACC Heart Fail 9:360–70
    [Google Scholar]
  124. 124. 
    Borlaug BA, Koepp KE, Melenovsky V. 2015. Sodium nitrite improves exercise hemodynamics and ventricular performance in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol. 66:1672–82
    [Google Scholar]
  125. 125. 
    Borlaug BA, Melenovsky V, Koepp KE. 2016. Inhaled sodium nitrite improves rest and exercise hemodynamics in heart failure with preserved ejection fraction. Circ. Res. 119:880–86
    [Google Scholar]
  126. 126. 
    Reddy YNV, Stewart GM, Obokata M et al. 2021. Peripheral and pulmonary effects of inorganic nitrite during exercise in heart failure with preserved ejection fraction. Eur. J. Heart Fail 23:81423
    [Google Scholar]
  127. 127. 
    Shah SJ, Kitzman DW, Borlaug BA et al. 2016. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation 134:73–90
    [Google Scholar]
  128. 128. 
    Sorimachi H, Omote K, Borlaug BA. 2021. Clinical phenogroups in heart failure with preserved ejection fraction. Heart Fail. Clin. 17:483–98
    [Google Scholar]
/content/journals/10.1146/annurev-med-042220-022745
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