Vol 27, No 5 (2020)
Experts' viewpoint
Published online: 2020-09-18

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On the search for the right definition of heart failure with preserved ejection fraction

Agnieszka Kapłon-Cieślicka12, Karolina Kupczyńska13, Piotr Dobrowolski14, Błażej Michalski13, Miłosz J. Jaguszewski15, Waldemar Banasiak16, Paweł Burchardt17, Łukasz Chrzanowski13, Szymon Darocha18, Justyna Domienik-Karłowicz19, Jarosław Drożdż110, Marcin Fijałkowski15, Krzysztof J. Filipiak12, Marcin Gruchała15, Ewa A. Jankowska111, Piotr Jankowski112, Jarosław D. Kasprzak13, Wojciech Kosmala113, Piotr Lipiec114, Przemysław Mitkowski115, Katarzyna Mizia-Stec116, Piotr Szymański117, Agnieszka Tycińska118, Wojciech Wańha119, Maciej Wybraniec116, Adam Witkowski120, Piotr Ponikowski111, On behalf of “Club 30” of the Polish Cardiac Society
Pubmed: 32986238
Cardiol J 2020;27(5):449-468.

Abstract

The definition of heart failure with preserved ejection fraction (HFpEF) has evolved from a clinically based “diagnosis of exclusion” to definitions focused on objective evidence of diastolic dysfunction and/or elevated left ventricular filling pressures. Despite advances in our understanding of HFpEF pathophysiology and the development of more sophisticated imaging modalities, the diagnosis of HFpEF remains challenging, especially in the chronic setting, given that symptoms are provoked by exertion and diagnostic evaluation is largely conducted at rest. Invasive hemodynamic study, and in particular — invasive exercise testing, is considered the reference method for HFpEF diagnosis. However, its use is limited as opposed to the high number of patients with suspected HFpEF. Thus, diagnostic criteria for HFpEF should be principally based on non-invasive measurements. As no single non-invasive variable can adequately corroborate or refute the diagnosis, different combinations of clinical, echocardiographic, and/or biochemical parameters have been introduced. Recent years have brought an abundance of HFpEF definitions. Here, we present and compare four of them: 1) the 2016 European Society of Cardiology criteria for HFpEF; 2) the 2016 echocardiographic algorithm for diagnosing diastolic dysfunction; 3) the 2018 evidence-based H2FPEF score; and 4) the most recent, 2019 Heart Failure Association HFA-PEFF algorithm. These definitions vary in their approach to diagnosis, as well as sensitivity and specificity. Further studies to validate and compare the diagnostic accuracy of HFpEF definitions are warranted. Nevertheless, it seems that the best HFpEF definition would originate from a randomized clinical trial showing a favorable effect of an intervention on prognosis in HFpEF.

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References

  1. Ponikowski P, Voors A, Anker S, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016; 37(27): 2129–2200.
  2. Lindenfeld J, Albert NM, Boehmer JP, et al. Heart Failure Society of America. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010; 16(6): e1–e194.
  3. Yancy C, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128(16).
  4. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29(4): 277–314.
  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 Heart J. 2019; 40(40): 3297–3317.
  6. Yusuf S, Pfeffer MA, Swedberg K, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003; 362(9386): 777–781.
  7. Redfield MM, Chen HH, Borlaug BA, et al. RELAX Trial. 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): 1268–1277.
  8. Pitt B, Pfeffer M, Assmann S, et al. Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2014; 370(15): 1383–1392.
  9. Carson P, Anand I, Win S, et al. The hospitalization burden and post-hospitalization mortality risk in heart failure with preserved ejection fraction. JACC: Heart Failure. 2015; 3(6): 429–441.
  10. Solomon SD, McMurray JJV, Anand IS, et al. PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019; 381(17): 1609–1620.
  11. Anker SD, Butler J, Filippatos GS, et al. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail. 2019; 21(10): 1279–1287.
  12. Senni M, Caravita S, Paulus WJ. Do existing definitions identify subgroup phenotypes or reflect the natural history of heart failure with preserved ejection fraction? Circulation. 2019; 140(5): 366–369.
  13. Lam CSP, Voors AA, de Boer RA, et al. Heart failure with preserved ejection fraction: from mechanisms to therapies. Eur Heart J. 2018; 39(30): 2780–2792.
  14. Carey SA, Bass K, Saracino G, et al. Probability of Accurate Heart Failure Diagnosis and the Implications for Hospital Readmissions. Am J Cardiol. 2017; 119(7): 1041–1046.
  15. Hage C, Löfström U, Donal E, et al. Do patients with acute heart failure and preserved ejection fraction have heart failure at follow-up: implications of the framingham criteria. J Card Fail. 2020; 26(8): 673–684.
  16. Kapłon-Cieślicka A, Tymińska A, Peller M, et al. Diagnosis, clinical course, and 1-year outcome in patients hospitalized for heart failure with preserved ejection fraction (from the Polish cohort of the European Society of Cardiology Heart Failure Long-Term Registry). Am J Cardiol. 2016; 118(4): 535–542.
  17. Kapłon-Cieślicka A, Laroche C, Crespo-Leiro MG, et al. Is heart failure misdiagnosed in hospitalized patients with preserved ejection fraction? From the European Society of Cardiology - Heart Failure Association EURObservational Research Programme Heart Failure Long-Term Registry. ESC Heart Fail. 2020 [Epub ahead of print].
  18. Verdú-Rotellar JM, Frigola-Capell E, Alvarez-Pérez R, et al. Validation of heart failure diagnosis registered in primary care records in two primary care centres in Barcelona (Spain) and factors related. A cross-sectional study. Eur J Gen Pract. 2017; 23(1): 107–113.
  19. Delekta J, Hansen SM, AlZuhairi KS, et al. The validity of the diagnosis of heart failure (I50.0-I50.9) in the Danish National Patient Register. Dan Med J. 2018; 65(4): pii: A5470.
  20. Ho JE, Zern EK, Wooster L, et al. Differential clinical profiles, exercise responses, and outcomes associated with existing HFpEF definitions. Circulation. 2019; 140(5): 353–365.
  21. Balaney B, Medvedofsky D, Mediratta A, et al. Invasive Validation of the Echocardiographic Assessment of Left Ventricular Filling Pressures Using the 2016 Diastolic Guidelines: Head-to-Head Comparison with the 2009 Guidelines. J Am Soc Echocardiogr. 2018; 31(1): 79–88.
  22. Andersen OS, Smiseth OA, Dokainish H, et al. Estimating Left Ventricular Filling Pressure by Echocardiography. J Am Coll Cardiol. 2017; 69(15): 1937–1948.
  23. Lancellotti P, Galderisi M, Edvardsen T, et al. Echo-Doppler estimation of left ventricular filling pressure: results of the multicentre EACVI Euro-Filling study. Eur Heart J Cardiovasc Imaging. 2017; 18(9): 961–968.
  24. Obokata M, Kane GC, Reddy YNV, et al. Role of diastolic stress testing in the evaluation for heart failure with preserved ejection fraction: a simultaneous invasive-echocardiographic study. Circulation. 2017; 135(9): 825–838.
  25. Nauta JF, Hummel YM, van der Meer P, et al. Correlation with invasive left ventricular filling pressures and prognostic relevance of the echocardiographic diastolic parameters used in the 2016 ESC heart failure guidelines and in the 2016 ASE/EACVI recommendations: a systematic review in patients with heart failure with preserved ejection fraction. Eur J Heart Fail. 2018; 20(9): 1303–1311.
  26. Sharifov OF, Schiros CG, Aban I, et al. Diagnostic accuracy of tissue doppler index E/e' for evaluating left ventricular filling pressure and diastolic dysfunction/heart failure with preserved ejection fraction: a systematic review and meta-analysis. J Am Heart Assoc. 2016; 5(1).
  27. Matsushita K, Minamishima T, Goda A, et al. Comparison of the reliability of E/E' to estimate pulmonary capillary wedge pressure in heart failure patients with preserved ejection fraction versus those with reduced ejection fraction. Int J Cardiovasc Imaging. 2015; 31(8): 1497–1502.
  28. Obokata M, Borlaug BA. The strengths and limitations of E/e' in heart failure with preserved ejection fraction. Eur J Heart Fail. 2018; 20(9): 1312–1314.
  29. Gao C, Tao Y, Pan J, et al. Evaluation of elevated left ventricular end diastolic pressure in patients with preserved ejection fraction using cardiac magnetic resonance. Eur Radiol. 2019; 29(5): 2360–2368.
  30. Sharifov OF, Gupta H. What is the evidence that the tissue Doppler index E/e' reflects left ventricular filling pressure changes after exercise or pharmacological intervention for evaluating diastolic function? A systematic review. J Am Heart Assoc. 2017; 6(3).
  31. Smiseth OA. Evaluation of left ventricular diastolic function: state of the art after 35 years with Doppler assessment. J Echocardiogr. 2018; 16(2): 55–64.
  32. Opdahl A, Remme EW, Helle-Valle T, et al. Determinants of left ventricular early-diastolic lengthening velocity: independent contributions from left ventricular relaxation, restoring forces, and lengthening load. Circulation. 2009; 119(19): 2578–2586.
  33. Graham RJ, Gelman JS, Donelan L, et al. Effect of preload reduction by haemodialysis on new indices of diastolic function. Clin Sci (Lond). 2003; 105(4): 499–506.
  34. D'Andrea A, Vriz O, Ferrara F, et al. Reference ranges and physiologic variations of left ' ratio in healthy adults: clinical and echocardiographic correlates. J Cardiovasc Echogr. 2018; 28(2): 101–108.
  35. Harada E, Mizuno Y, Kugimiya F, et al. Sex differences in heart failure with preserved ejection fraction reflected by B-type natriuretic peptide level. Am J Med Sci. 2018; 356(4): 335–343.
  36. Anjan VY, Loftus TM, Burke MA, et al. Prevalence, clinical phenotype, and outcomes associated with normal B-type natriuretic peptide levels in heart failure with preserved ejection fraction. Am J Cardiol. 2012; 110(6): 870–876.
  37. Maisel A, Mueller C, Adams K, et al. State of the art: using natriuretic peptide levels in clinical practice. Eur J Heart Fail. 2008; 10(9): 824–839.
  38. Meijers WC, Hoekstra T, Jaarsma T, et al. Patients with heart failure with preserved ejection fraction and low levels of natriuretic peptides. Neth Heart J. 2016; 24(4): 287–295.
  39. Borlaug B, Nishimura R, Sorajja P, et al. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circulation: Heart Failure. 2010; 3(5): 588–595.
  40. Zaphiriou A, Robb S, Murray-Thomas T, et al. The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study. Eur J Heart Fail. 2005; 7(4): 537–541.
  41. Barberato SH, Mantilla DEV, Misocami MA, et al. Effect of preload reduction by hemodialysis on left atrial volume and echocardiographic Doppler parameters in patients with end-stage renal disease. Am J Cardiol. 2004; 94(9): 1208–1210.
  42. Fijalkowski M, Koprowski A, Gruchala M, et al. Effect of preload reduction by hemodialysis on myocardial ultrasonic characterization, left atrial volume, and Doppler tissue imaging in patients with end-stage renal disease. J Am Soc Echocardiogr. 2006; 19(11): 1359–1364.
  43. Lam CSP, Borlaug BA, Kane GC, et al. Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation. 2009; 119(20): 2663–2670.
  44. D'Alto M, Romeo E, Argiento P, et al. Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. Int J Cardiol. 2013; 168(4): 4058–4062.
  45. Fisher MR, Forfia PR, Chamera E, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med. 2009; 179(7): 615–621.
  46. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015; 46(4): 903–975.
  47. Kjaergaard J, Snyder EM, Hassager C, et al. Impact of preload and afterload on global and regional right ventricular function and pressure: a quantitative echocardiography study. J Am Soc Echocardiogr. 2006; 19(5): 515–521.
  48. Paulus WJ, van Ballegoij JJM. Treatment of heart failure with normal ejection fraction: an inconvenient truth! J Am Coll Cardiol. 2010; 55(6): 526–537.
  49. Kovacs G, Herve P, Barbera JA, et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J. 2017; 50(5).
  50. Forfia PR, Watkins SP, Rame JE, et al. Relationship between B-type natriuretic peptides and pulmonary capillary wedge pressure in the intensive care unit. J Am Coll Cardiol. 2005; 45(10): 1667–1671.
  51. Chetrit M, Cremer PC, Klein AL. Imaging of diastolic dysfunction in community-based epidemiological studies and randomized controlled trials of HFpEF. JACC Cardiovasc Imaging. 2020; 13(1 Pt 2): 310–326.
  52. Pinedo M, Villacorta E, Tapia C, et al. Inter- and intra-observer variability in the echocardiographic evaluation of right ventricular function. Rev Esp Cardiol. 2010; 63(7): 802–809.
  53. Olmos-Temois SG, Santos-Martínez LE, Álvarez-Álvarez R, et al. Interobserver agreement on the echocardiographic parameters that estimate right ventricular systolic function in the early postoperative period of cardiac surgery. Med Intensiva. 2016; 40(8): 491–498.
  54. Reddy YNV, Carter RE, Obokata M, et al. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation. 2018; 138(9): 861–870.
  55. Li S, Churchill T, Curreri L, et al. Diagnosing HFpEF: validation of a noninvasive diagnostic approach against invasive hemodynamics. J Am Coll Cardiol. 2020; 75(11): 911.
  56. Nagueh S, Appleton C, Gillebert T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009; 22(2): 107–133.
  57. Sepehrvand N, Alemayehu W, Dyck GJB, et al. External validation of the HF-PEF model in diagnosing patients with heart failure and preserved ejection fraction. Circulation. 2019; 139(20): 2377–2379.
  58. Sueta D, Yamamoto E, Nishihara T, et al. H2FPEF score as a prognostic value in hfpef patients. Am J Hypertens. 2019; 32(11): 1082–1090.
  59. Suzuki S, Kaikita K, Yamamoto E, et al. H FPEF score for predicting future heart failure in stable outpatients with cardiovascular risk factors. ESC Heart Fail. 2020; 7(1): 65–74.
  60. Tao Y, Wang W, Zhu J, et al. HFPEF score predicts 1-year rehospitalisation of patients with heart failure with preserved ejection fraction. Postgrad Med J. 2020 [Epub ahead of print].
  61. Morris DA, Ma XX, Belyavskiy E, et al. Left ventricular longitudinal systolic function analysed by 2D speckle-tracking echocardiography in heart failure with preserved ejection fraction: a meta-analysis. Open Heart. 2017; 4(2): e000630.
  62. 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.
  63. Tschöpe C, Senni M. Usefulness and clinical relevance of left ventricular global longitudinal systolic strain in patients with heart failure with preserved ejection fraction. Heart Fail Rev. 2020; 25(1): 67–73.
  64. Kosmala W, Rojek A, Przewlocka-Kosmala M, et al. Contributions of nondiastolic factors to exercise intolerance in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2016; 67(6): 659–670.
  65. Przewlocka-Kosmala M, Marwick TH, Dabrowski A, et al. Contribution of cardiovascular reserve to prognostic categories of heart failure with preserved ejection fraction: a classification based on machine learning. J Am Soc Echocardiogr. 2019; 32(5): 604–615.e6.
  66. 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): 413–421.
  67. Oh JK, Miranda WR, Bird JG, et al. The 2016 diastolic function guideline: is it already time to revisit or revise them? JACC Cardiovasc Imaging. 2020; 13(1 Pt 2): 327–335.
  68. Ouwerkerk W, Tromp J, Jin X, et al. Heart failure with preserved ejection fraction diagnostic scores in an Asian population. Eur J Heart Fail. 2020 [Epub ahead of print].
  69. Tromp J, Teng TH, Tay WT, et al. ASIAN-HF Investigators. Heart failure with preserved ejection fraction in Asia. Eur J Heart Fail. 2019; 21(1): 23–36.
  70. McHugh K, DeVore AD, Wu J, et al. Heart failure with preserved ejection fraction and diabetes: JACC state-of-the-art review. J Am Coll Cardiol. 2019; 73(5): 602–611.
  71. Lam CSP, Donal E, Kraigher-Krainer E, et al. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011; 13(1): 18–28.
  72. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017; 14(10): 591–602.
  73. Gerber Y, Weston SA, Redfield MM, et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med. 2015; 175(6): 996–1004.
  74. Fukuma N, Takimoto E, Ueda K, et al. Estrogen receptor-α non-nuclear signaling confers cardioprotection and Is Essential to cGMP-PDE5 inhibition efficacy. JACC Basic Transl Sci. 2020; 5(3): 282–295.
  75. Barton M, Meyer MR. Heart Failure with preserved ejection fraction in women: new clues to causes and treatment. JACC Basic Transl Sci. 2020; 5(3): 296–299.
  76. Sabbatini AR, Kararigas G. Menopause-Related estrogen decrease and the pathogenesis of HFpEF: JACC review topic of the week. J Am Coll Cardiol. 2020; 75(9): 1074–1082.
  77. Beale AL, Nanayakkara S, Segan L, et al. Sex differences in heart failure with preserved ejection fraction pathophysiology: a detailed invasive hemodynamic and echocardiographic analysis. JACC Heart Fail. 2019; 7(3): 239–249.
  78. Obokata M, Reddy YNV, Pislaru SV, et al. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017; 136(1): 6–19.
  79. Reddy YNV, Lewis GD, Shah SJ, et al. Characterization of the obese phenotype of heart failure with preserved ejection fraction: a RELAX trial ancillary study. Mayo Clin Proc. 2019; 94(7): 1199–1209.
  80. Zafrir B, Lund LH, Laroche C, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry. Eur Heart J. 2018; 39(48): 4277–4284.
  81. Sartipy U, Dahlström U, Fu M, et al. Atrial fibrillation in heart failure with preserved, mid-range, and reduced ejection fraction. JACC Heart Fail. 2017; 5(8): 565–574.
  82. Kirchhof P, Benussi S, Kotecha D, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016; 37(38): 2893–2962.
  83. Dobrowolski P, Florczak E, Klisiewicz A, et al. Factors associated with diastolic dysfunction in patients with resistant hypertension: resist-POL study. Am J Hypertens. 2015; 28(3): 307–311.
  84. Bristow MR, Enciso JS, Gersh BJ, et al. Detection and Management of Geographic Disparities in the TOPCAT Trial: Lessons Learned and Derivative Recommendations. JACC Basic Transl Sci. 2016; 1(3): 180–189.
  85. Cleland J, Tendera M, Adamus J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006; 27(19): 2338–2345.
  86. Kosmala W. Diagnosing HFpEF: On Track at Last? JACC Cardiovasc Imaging. 2018; 11(4): 586–588.
  87. van Heerebeek L, Paulus WJ. Understanding heart failure with preserved ejection fraction: where are we today? Neth Heart J. 2016; 24(4): 227–236.
  88. 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): 97–98.
  89. Tromp J, Tay WT, Ouwerkerk W, et al. Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry. PLoS Med. 2018; 15(3): e1002541.
  90. Shah S, Katz D, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015; 131(3): 269–279.
  91. Samson R, Jaiswal A, Ennezat PV, et al. Clinical phenotypes in heart failure with preserved ejection fraction. J Am Heart Assoc. 2016; 5(1).
  92. Michalski B, Trzciński P, Kupczyńska K, et al. The differences in the relationship between diastolic dysfunction, selected biomarkers and collagen turn-over in heart failure patients with preserved and reduced ejection fraction. Cardiol J. 2017; 24(1): 35–42.