Heart Failure with Perserved Ejection Fraction Current Diagnostic and Therapeutic Approaches
https://doi.org/10.20996/1819-6446-2021-05-01
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Little progress has been in the treatment of this condition since its introduction some 30 years ago. It's accepted that HFpEF is heterogeneous in many ways, ethologically and phenotypically. The underlying mechanisms of the syndrome are not clear. Recently, it has been shown that the diagnostic criteria for HFpEF lacks sensitivity and specificity. Novel treatment approaches, which were developed based on current HFpEF pathophysiological concepts, did not show either clinical or prognostic benefit for patients. Therefore, there is an urgent need to revise current diagnostic approaches and to further investigate the underlying mechanisms. Recently, two novel diagnostic score systems were proposed: H2PEF and HFA-PEFF. Recently, a number of phase II and III randomized control trials have been completed. Here, the authors discuss the potential novel diagnostic approaches to HFpEF and treatment perspectives.
About the Authors
A. A. ShchendryginaRussian Federation
Anastasia A. Shchendrygina - eLibrary SPIN: 2137-5623
K. A. Zhbanov
Russian Federation
Konstantin A. Zhbanov
E. V. Privalova
Russian Federation
Elena V. Privalova
A. O. Yusupova
Russian Federation
Alfiya O. Yusupova
Yu. A. Danilogorskaya
Russian Federation
Yulia A. Danilogorskaya
E. Yu. Salakheeva
Russian Federation
Ekaterina Yu. Salakheeva
I. Ya. Sokolova
Russian Federation
Irina Ya. Sokolova
S. A. Tsatsurova
Russian Federation
Sabrina A. Tsatsurova
A. A. Ageeva
Russian Federation
Anastasia A. Ageeva
Yu. N. Belenkov
Russian Federation
Yuri N. Belenkov
References
1. 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083 (In Russ.) DOI:10.15829/1560-4071-2020-4083.
2. Mareev VYu, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8- 158 (In Russ.) DOI:10.18087/cardio.2475.
3. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37(27):2129-2200. DOI:10.1093/eurheartj/ehw128.
4. 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. DOI:10.1093/eurheartj/ehz641.
5. Brunner-La Rocca HP, Sandersvan Wijk S. BNP guided therapy review. Card Fail Rev. 2019;5(1):44.
6. Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation. 2015;131(1):34-42. DOI:10.1161/CIRCULATIONAHA.114.013255.
7. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609-20. DOI:10.1056/nejmoa1908655.
8. Meyer M, Lewinter MM. Heart rate and heart failure with preserved ejection fraction: Time to slow β-blocker use? Circ Hear Fail. 2019;12(8):1-5. DOI:10.1161/CIRCHEARTFAILURE.119.006213.
9. Ho JE, Zern EK, Wooster L, et al. Differential Clinical Profiles, Exercise Responses, and Outcomes Associated with Existing HFpEF Definitions. Circulation. 2019;140(5):353-65. DOI:10.1161/CIRCULATIONAHA.118.039136.
10. Borlaug BA, Nishimura RA, Sorajja P, et al. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Hear Fail. 2010;3(5):588-95. DOI:10.1161/CIRCHEARTFAILURE.109.930701.
11. Verbrugge FH, Guazzi M, Testani JM, Borlaug BA. Altered Hemodynamics and End-Organ Damage in Heart Failure: Impact on the Lung and Kidney. Circulation. Published online 2020:998-1012. DOI:10.1161/CIRCULATIONAHA.119.045409.
12. 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. DOI:10.1016/j.echo.2016.01.011.
13. Gustafsson F, Steensgaard-Hansen F, Badskjaer J, et al. Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure. J Card Fail. 2005;11(5 Suppl):15-20. DOI:10.1016/j.cardfail.2005.04.022.
14. 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):870-6. DOI:10.1016/j.amjcard.2012.05.014.
15. Mueller C, McDonald K, de Boer RA, et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail. 2019;21(6):715-31. DOI:10.1002/ejhf.1494.
16. Ha JW, Andersen OS, Smiseth OA. Diastolic Stress Test: Invasive and Noninvasive Testing. JACC Cardiovasc Imaging. 2020;13(1):272-82. DOI:10.1016/j.jcmg.2019.01.037.
17. Pellicori P, Platz E, Dauw J, et al. Ultrasound imaging of congestion in heart failure: examinations beyond the heart. Eur J Heart Fail. 2020;10.1002/ejhf.2032. DOI:10.1002/ejhf.2032.
18. 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. DOI:10.1161/CIRCULATIONAHA.118.034646.
19. Ezekowitz JA, Becher H, Belenkie I, et al. The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study. BMC Cardiovasc Disord. 2014;14(1):1-9. DOI:10.1186/1471-2261-14-91.
20. Sepehrvand N, Alemayehu W, Dyck GJB, et al. External Validation of the H2F-PEF Model in Diagnosing Patients with Heart Failure and Preserved Ejection Fraction. Circulation. 2019;139(20):2377-2379. DOI:10.1161/CIRCULATIONAHA.118.038594.
21. Segar MW, Patel KV, Berry JD, et al. Generalizability and Implications of the H2FPEF Score in a Cohort of Patients with Heart Failure with Preserved Ejection Fraction: Insights from the TOPCAT Trial. Circulation. 2019;139(15):1851-1853. DOI:10.1161/CIRCULATIONAHA.118.039051
22. 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. DOI:10.1002/ejhf.1614
23. Seo M, Yamada T, Tamaki S, et al. Prognostic Significance of Serum Cholinesterase Level in Patients With Acute Decompensated Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry. J Am Heart Assoc. 2020;9(1):e014100. DOI:10.1161/JAHA.119.014100
24. Iwakura K, Onishi T, Okada M, et al. Validation of the HFA-PEFF- and H2FPEF score in Japanese patients with heart failure with preserved ejection fraction. Eur Heart J. 2020;41(Supplement_2): 2020. DOI:10.1093/ehjci/ehaa946.0998
25. Selvaraj S, Myhre PL, Vaduganathan M, et al. Application of Diagnostic Algorithms for Heart Failure With Preserved Ejection Fraction to the Community. JACC Hear Fail. 2020;8(8):640-53. DOI:10.1016/j.jchf.2020.03.013
26. TOPCAT: FDA Briefing Document Cardiovascular and Renal Drugs Advisory Committee Meeting Spironolactone for Heart Failure with Preserved Ejection Fraction (HFpEF). Published online 2020. [cited by Feb 20, 2021]. Available from: https://www.fda.gov/media/144411/download.
27. FDA Briefing Document Cardiovascular and Renal Drugs Advisory Committee Meeting. Published online 2014:205 [cited by Feb 20, 2021]. Available from: https://www.fda.gov/media/133297/download.
28. Rivas-Lasarte M, Álvarez-García J, Fernández-Martínez J, et al. Lung ultrasound-guided treatment in ambulatory patients with heart failure: a randomized controlled clinical trial (LUS-HF study). Eur J Heart Fail. 2019;21(12):1605-1613. DOI:10.1002/ejhf.1604.
29. Wachter R, Schmidt-Schweda S, Westermann D, et al. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure. Eur Heart J. 2009;30(24):3027-3036. DOI:10.1093/eurheartj/ehp341.
30. Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation. 2006;114(20):2138-47. DOI:10.1161/CIRCULATIONAHA.106.632745.
31. 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. DOI:10.1016/j.jacc.2013.02.092
32. Borlaug BA, Anstrom KJ, Lewis GD, et al. Effect of Inorganic Nitrite vs Placebo on Exercise Capacity among Patients with Heart Failure with Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial. J Am Med Assoc. 2018;320(17):1764-73. DOI:10.1001/jama.2018.14852.
33. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): A double-blind, phase 3, random. Lancet Oncol. 2012;13(3):247-55. DOI:10.1016/S1470-2045(12)70063-3.
34. Udelson JE, Lewis GD, Shah SJ, et al. Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients with Heart Failure with Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial. J Am Med Assoc. 2020;324(15):1522-31. DOI:10.1001/jama.2020.16641
35. Armstrong PW, Lam CSP, Anstrom KJ, et al. Effect of Vericiguat vs Placebo on Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. J Am Med Assoc. 2020;324(15):1512-21. DOI:10.1001/jama.2020.15922.
36. Redfield MM, Chen HH, Borlaug BA, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: A randomized clinical trial. J Am Med Assoc. 2013;309(12):1268-77. DOI:10.1001/jama.2013.2024.
37. Van Tassell BW, Buckley LF, Carbone S, et al. Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (DHART2). Clin Cardiol. 2017;40(9):626-32. DOI:10.1002/clc.22719.
38. Melenovsky V, Hwang SJ, Lin G, et al. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014;35(48):3452-62. DOI:10.1093/eurheartj/ehu193.
39. Obokata M, Reddy YNV, Melenovsky V, et al. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction. Eur Heart J. 2019;40(8):689- 98. DOI:10.1093/eurheartj/ehy809.
40. Shah AM, Claggett B, Sweitzer NK, et al. Prognostic Importance of Impaired Systolic Function in Heart Failure with Preserved Ejection Fraction and the Impact of Spironolactone. Circulation. 2015;132(5):402-14. DOI:10.1161/CIRCULATIONAHA.115.015884.
41. Kalra R, Gupta K, Sheets R, et al. Cardiac Function and Sudden Cardiac Death in Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial). Am J Cardiol. 2020;129:46-52. DOI:10.1016/j.amjcard.2020.04.038.
42. Park JJ, Park CS, Mebazaa A, et al. Characteristics and outcomes of HFpEF with declining ejection fraction. Clin Res Cardiol. 2020;109(2):225-34. DOI:10.1007/s00392-019-01505-y.
43. Shah SJ. 20th Annual Feigenbaum Lecture: Echocardiography for Precision Medicine—Digital Biopsy to Deconstruct Biology. J Am Soc Echocardiogr. 2019;32(11):1379-95.e2. DOI:10.1016/j.echo.2019.08.002.
44. Cohen JB, Schrauben SJ, Zhao L, et al. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone. JACC Hear Fail. 2020;8(3):172-84. DOI:10.1016/j.jchf.2019.09.009.
45. Shah SJ, Katz DH, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015;131(3):269-79. DOI:10.1161/CIRCULATIONAHA.114.010637.
46. Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021;384(2):117-28. DOI:10.1056/nejmoa2030183.
Review
For citations:
Shchendrygina A.A., Zhbanov K.A., Privalova E.V., Yusupova A.O., Danilogorskaya Yu.A., Salakheeva E.Yu., Sokolova I.Y., Tsatsurova S.A., Ageeva A.A., Belenkov Yu.N. Heart Failure with Perserved Ejection Fraction Current Diagnostic and Therapeutic Approaches. Rational Pharmacotherapy in Cardiology. 2021;17(3):476-483. (In Russ.) https://doi.org/10.20996/1819-6446-2021-05-01