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image of Impacts of Sacubitril-Valsartan versus Valsartan on Left Ventricular Remodeling and Cardiac Function in Patients with Ischemic Heart Failure and Reduced Ejection Fraction: A Randomized Double-blinded Controlled Trial

Abstract

Introduction

Sacubitril/valsartan (SAC/VAL) is a combination medication primarily used to treat heart failure with reduced ejection fraction (HFrEF). This randomized controlled trial (RCT) assessed the impacts of SAC/VAL compared with valsartan (VAL) on left ventricular (LV) remodeling, clinical outcomes, and cardiac function in patients with HFrEF.

Methods

A single-blinded run-in phase and a double-blinded treatment phase were conducted at Imam Hospital (Ahvaz, Iran) among 106 patients (SAC/VAL group: n=54; VAL group=52). Patients were randomly assigned to receive a combination of SAC/VAL (up-titrated to the target dosage of 200 mg, twice daily) or VAL (up-titrated to 160 mg, twice daily) for a six-month of intervention. Patients' clinical, demographic, and echocardiographic data were collected before and after the intervention.

Results

After a six-month intervention, statistically significant mean differences were detected in various echocardiographic parameters (., LV end-systolic volume, LV ejection fraction, and LV end-diastolic volume) within each group and between the two groups. Significant mean differences were noted in the six-minute walk test, serum levels of blood urea nitrogen, aspartate aminotransferase, sodium, creatinine, alanine aminotransferase, N-terminal pro–B-type natriuretic peptide, and scores of the Kansas City Cardiomyopathy questionnaire in post-intervention assessments within each group and between the two groups ( <0.05). There was a substantial within-group difference in the frequency of the New York Heart Association (NYHA) functional class from pre- to post-intervention ( <0.05).

Discussion

This study revealed that SAC/VAL exhibited superior efficacy compared to VAL. However, the follow-up period was relatively short, and the potential risks associated with the prolonged administration of this medication have not been thoroughly evaluated.

Conclusion

This RCT indicated that the combination of SAC/VAL had better therapeutic effects than VAL on LV remodeling, clinical outcomes, and cardiac function in patients with ischemic HFrEF. These findings may help refine treatment priorities for patients with HFrEF and improve the quality of their care.

Clinical Trial Registration Number

IRCT20240117060713N1.

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2025-08-13
2025-10-29
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References

  1. Kurmani S. Squire I. Acute heart failure: Definition, classification and epidemiology. Curr. Heart Fail. Rep. 2017 14 5 385 392 10.1007/s11897‑017‑0351‑y 28785969
    [Google Scholar]
  2. Chen L.M. Levine D.A. Hayward R. Cox M. Schulte P.J. DeVore A.D. Hernandez A. Heidenreich P.A. Yancy C. Fonarow G.C. Relationship between hospital 30‐day mortality rates for heart failure and patterns of early inpatient comfort care. J. Hosp. Med. 2018 13 3 170 176 10.12788/jhm.2862 29505624
    [Google Scholar]
  3. Liu L-W. Wu P.C. Chiu M.Y. Tu P.F. Fang C.C. Sacubitril/valsartan improves left ventricular ejection fraction and reverses cardiac remodeling in Taiwanese patients with heart failure and reduced ejection fraction. Zhonghua Minguo Xinzangxue Hui Zazhi 2020 36 2 125 132 10.6515/ACS.202003_36(2).20190812A 32201463
    [Google Scholar]
  4. Rush C.J. Berry C. Oldroyd K.G. Rocchiccioli J.P. Lindsay M.M. Touyz R.M. Murphy C.L. Ford T.J. Sidik N. McEntegart M.B. Lang N.N. Jhund P.S. Campbell R.T. McMurray J.J.V. Petrie M.C. Prevalence of coronary artery disease and coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction. JAMA Cardiol. 2021 6 10 1130 1143 10.1001/jamacardio.2021.1825 34160566
    [Google Scholar]
  5. Oka T. Akazawa H. Naito A.T. Komuro I. Angiogenesis and cardiac hypertrophy: Maintenance of cardiac function and causative roles in heart failure. Circ. Res. 2014 114 3 565 571 10.1161/CIRCRESAHA.114.300507 24481846
    [Google Scholar]
  6. Zheng X. Wang S. Zou X. Jing Y. Yang R. Li S. Wang F. Ginsenoside Rb1 improves cardiac function and remodeling in heart failure. Exp. Anim. 2017 66 3 217 228 10.1538/expanim.16‑0121 28367863
    [Google Scholar]
  7. Ma T. Zhu D. Chen D. Zhang Q. Dong H. Wu W. Lu H. Wu G. Sulforaphane, a natural isothiocyanate compound, improves cardiac function and remodeling by inhibiting oxidative stress and inflammation in a rabbit model of chronic heart failure. Med. Sci. Monit. 2018 24 1473 1483 10.12659/MSM.906123 29527002
    [Google Scholar]
  8. Bertero E. Maack C. Metabolic remodelling in heart failure. Nat. Rev. Cardiol. 2018 15 8 457 470 10.1038/s41569‑018‑0044‑6 29915254
    [Google Scholar]
  9. Curtis J.P. Sokol S.I. Wang Y. Rathore S.S. Ko D.T. Jadbabaie F. Portnay E.L. Marshalko S.J. Radford M.J. Krumholz H.M. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure. J. Am. Coll. Cardiol. 2003 42 4 736 742 10.1016/S0735‑1097(03)00789‑7 12932612
    [Google Scholar]
  10. Tsai C.H. Pan C.T. Chang Y.Y. Chen Z.W. Wu V.C. Hung C.S. Lin Y.H. Left ventricular remodeling and dysfunction in primary aldosteronism. J. Hum. Hypertens. 2021 35 2 131 147 10.1038/s41371‑020‑00426‑y 33067554
    [Google Scholar]
  11. Shah A.M. Cikes M. Prasad N. Li G. Getchevski S. Claggett B. Rizkala A. Lukashevich I. O’Meara E. Ryan J.J. Shah S.J. Mullens W. Zile M.R. Lam C.S.P. McMurray J.J.V. Solomon S.D. Echocardiographic features of patients with heart failure and preserved left ventricular ejection fraction. J. Am. Coll. Cardiol. 2019 74 23 2858 2873 10.1016/j.jacc.2019.09.063 31806129
    [Google Scholar]
  12. Aimo A. Gaggin H.K. Barison A. Emdin M. Januzzi J.L. Imaging, biomarker, and clinical predictors of cardiac remodeling in heart failure with reduced ejection fraction. JACC Heart Fail. 2019 7 9 782 794 10.1016/j.jchf.2019.06.004 31401101
    [Google Scholar]
  13. Chen F. Tian G. Bai X. Li J. Yuan Z. The effect of Sacubitril/Valsartan on cardiac function and cardiac remodeling in patients with heart failure with reduced ejection fraction. Ann. Palliat. Med. 2021 10 8 8684 8691 10.21037/apm‑21‑157 34488357
    [Google Scholar]
  14. Boulet J. Mehra M.R. Left ventricular reverse remodeling in heart failure: Remission to recovery. Struct. Heart. 2021 5 5 466 481 10.1080/24748706.2021.1954275
    [Google Scholar]
  15. McMurray J.J.V. Packer M. Desai A.S. Gong J. Lefkowitz M.P. Rizkala A.R. Rouleau J.L. Shi V.C. Solomon S.D. Swedberg K. Zile M.R. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med. 2014 371 11 993 1004 10.1056/NEJMoa1409077 25176015
    [Google Scholar]
  16. Felker G.M. Butler J. Ibrahim N.E. Piña I.L. Maisel A. Bapat D. Camacho A. Ward J.H. Williamson K.M. Solomon S.D. Januzzi J.L. Implantable cardioverter-defibrillator eligibility after initiation of sacubitril/valsartan in chronic heart failure: Insights from PROVE-HF. Circulation 2021 144 2 180 182 10.1161/CIRCULATIONAHA.121.054034 34251893
    [Google Scholar]
  17. Khder Y. Shi V. McMurray J.J.V. Lefkowitz M.P. Sacubitril/valsartan (LCZ696) in heart failure. Handb. Exp. Pharmacol. 2016 243 133 165 10.1007/164_2016_77 28004291
    [Google Scholar]
  18. Docherty K.F. Vaduganathan M. Solomon S.D. McMurray J.J.V. Sacubitril/Valsartan. JACC Heart Fail. 2020 8 10 800 810 10.1016/j.jchf.2020.06.020 33004114
    [Google Scholar]
  19. Sauer A.J. Cole R. Jensen B.C. Pal J. Sharma N. Yehya A. Vader J. Practical guidance on the use of sacubitril/valsartan for heart failure. Heart Fail. Rev. 2019 24 2 167 176 10.1007/s10741‑018‑9757‑1 30565021
    [Google Scholar]
  20. Wachter R. Senni M. Belohlavek J. Straburzynska-Migaj E. Witte K.K. Kobalava Z. Fonseca C. Goncalvesova E. Cavusoglu Y. Fernandez A. Chaaban S. Bøhmer E. Pouleur A.C. Mueller C. Tribouilloy C. Lonn E. A L Buraiki J. Gniot J. Mozheiko M. Lelonek M. Noè A. Schwende H. Bao W. Butylin D. Pascual-Figal D. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: Primary results of the randomised TRANSITION study. Eur. J. Heart Fail. 2019 21 8 998 1007 10.1002/ejhf.1498 31134724
    [Google Scholar]
  21. Solomon S.D. Zile M. Pieske B. Voors A. Shah A. Kraigher-Krainer E. Shi V. Bransford T. Takeuchi M. Gong J. Lefkowitz M. Packer M. McMurray J.J.V. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. Lancet 2012 380 9851 1387 1395 10.1016/S0140‑6736(12)61227‑6 22932717
    [Google Scholar]
  22. Solomon S.D. McMurray J.J.V. Anand I.S. Ge J. Lam C.S.P. Maggioni A.P. Martinez F. Packer M. Pfeffer M.A. Pieske B. Redfield M.M. Rouleau J.L. van Veldhuisen D.J. Zannad F. Zile M.R. Desai A.S. Claggett B. Jhund P.S. Boytsov S.A. Comin-Colet J. Cleland J. Düngen H.D. Goncalvesova E. Katova T. Kerr Saraiva J.F. Lelonek M. Merkely B. Senni M. Shah S.J. Zhou J. Rizkala A.R. Gong J. Shi V.C. Lefkowitz M.P. Angiotensin–neprilysin inhibition in heart failure with preserved ejection fraction. N. Engl. J. Med. 2019 381 17 1609 1620 10.1056/NEJMoa1908655 31475794
    [Google Scholar]
  23. Pieske B. Wachter R. Shah S.J. Baldridge A. Szeczoedy P. Ibram G. Shi V. Zhao Z. Cowie M.R. Prado A.C. Wenetz L.M.M. Brasca D.G. Albisu J.P. Fernandez A.A. Liberman A. Echeverria G. Bartolacci I. Ranz M. Pedrotti M. Tapia D. Robertson M. Exposito S. Barrionuevo M. Resk J.H. Mercau G. Fuente R.L. Avaca H. Poy C. Hominal M.A. Cursack G. Vogelmann O.A. Casas M.M. Costantino M. Chiriffe J. Zweiker R. Motloch L.J. Auer J. Siostrzonek P. Grander W. Derthoo D. Mullens W. Vandekerckhove H. Maamar R. Delforge M. Mulleners T. Rassi S. Kormann A.P.M. Moraes A. Manenti E.R.F. Reis G. Maia L.N. Simoes M.V. Silva R.P. Danzmann L.C. Saraiva J.F.K. Sternieri M.C.V.B.B. de Souza W.B. Figueiredo E.L. Tzekova M.L. Boeva B. Vasilev D. Gospodinova S.T.T. Milanova M.H. Kabakchieva V.M. Valchanova P.I. Dimov B. Petrovsky P. Georgiev P.G. Spasova N. Mazhdrakov G. Konteva M. Benov H.O. Denchev S.V. Parent M. Demers C. Dion D. Bourgeois R.L. Heffernan M.L. Silgado G.A.M. Quiroz F. Cadena A. Mendoza J.L.A. Saldarriaga C. Arana C. Nechvatal L. Linhartova K. Klimsa Z. Busak L. Marek D. Slaby J. Polasek R. Koleckar P. Carda J. Kaislerova M. Trestik P. Zajicek P. Kuchar J. Vondrak J. Krupicka J. Brychta T. Lang P. Rickers H. Hove J.D. Gustafsson I. Nielsen O.W. Uuetoa T. Noodla S. Rosenthal A. Vettus R. Fauchier L. Aboyans V. Dutoiu T.M. Decoulx E. Geeter G.D. Khanoyan P. Donal E. Rosamel Y. Berthelot E. Seronde M-F. Winkelmann B.R. Grosskopf W. Haas J. Schmitt B. Jahnke N. Wilke A. Simonis G. Bosiljanoff P. Proskynitopoulos N. Axthelm C. Schenkenberger I. Proepper F. Frey N. Edelmann F. Fechtrup C. Graf T. Seidel M. Fehske W. Prohaska M. Unsoeld B. Birner C. Jungmair W. Hoelscher A. Kadel C. Lahiri K. Mehling H. Hagenow A. Naudts I.F.K. Winkler J. Salbach P. Naumann R. Killat H. Bastian D. Baeumer A.T. Goldmann B. Cuneo A. Hoepfner F. Noutsias M. Beermann J. Rieker W. Buckert D. Woehrle J. Westphal J. Bekfani T. Stoerk S. Schnupp S. Stoehring R. Neumann T. Knapp M. Bourgeois J. Edel K. Sarnighausen H-E. Nitschke T. Jeserich M. Ebelt H. Linke A. Gaub R. Sueselbeck T. Stratmann M. Toursarkissian N. Steinebach I. Krackhardt F. Schueler R. Brandt M. Placke J. Stangl V. Schoebel C. Tschoepe D. Overhoff U. Stenzel G. Stellbrink C. Schwefer M. Lorenz E. Uebel P. Gluesing D. Weissbrodt M. John F. Arango J.L. Castellanos J.M. Chang C. Haase F. Lopez E.M. Ovando A. Paniagua V. Vogel M. Estrada M.A.R. Rodriguez I. Corona V. Takacs J. Varga A. Nyolczas N. Kalina A. Nagy A.C. Merkely B. Mehta A. Chopada M.B. Ghaisas N.K. Sethi R. Basavanna D. Devasia T. Agarwal D.K. Bhalani N.C. Shah U.G. Chanana B.B. Washimkar S.N. Bental T. Goland S. Azzam Z. Weinstein J.M. Magen E. Gal T.B. Fucili A. Pedretti R.F.E. Servi S.D. Baronio B. Gronda E. Barbagallo M. Margonato A. Cosmi F. Giannattasio C. Pavan D. Mazza A. Ramazzina E. Senni M. Inserra C.A. Argiolas G. Borghi C. Sime I. Veze I. Mora L. Pontaga N. Plisiene J. Celutkiene J. Cepinskiene L. Leon J.L.A. Leon S. Padilla F. Cerda R.C. Linssen G. Jansen A. Hermans W. Bellersen L. Meer P.V. Lok D.J.A. Olimulder M. Hal J.M.C. Troquay R. de Bie M. Heerebeek L. Flores R.M.C. Camacho D.L.A. Rodriguez A. Alarco W. Lu L.I. Osores J.J.A.L. Cabrera W. Gaspar A. Martins J. Sarmento P. Fonseca C. Brito D. Marques I. Leao S. Nascimento A. Andrade A. Nica N.C. Ciobotaru G.V. Coman S.I. Copaci I. Dumitrascu A. Iosipescu L. Jurcut R. Militaru C. Podoleanu C. Stanciulescu G. Tomescu M.C. Tudoran M. Voicu O.C. Giuca A. Mercea C.D. Teodorescu I. Shvarts Y.G. Gapon L.I. Izmozherova N.V. Khaisheva L.A. Nosov V.P. Mozheiko M.E. Shutemova E.A. Privalov D.V. Baglikov A. Kastanayan A.A. Kobalava Z. Koziolova N.A. Zotov D.D. Lipchenko A. Burova N.N. Polezhaeva N. Pavlova I. Ermoshkina L.G. Zrazhevsky K.N. Boldueva S.A. Akatova E.V. Martsevich S.Y. Apostolovic S. Boskovic S. Davidovic G. Deljanin-Ilic M. Ilic A. Dzupina A. Fulop P. Jesensky T. Nociar J. Predmerska A. Schichorova J. Sokolova B. Lukacova J. Smik R. Stofkova D. Kolikova V. Papincak J. Sabo L. Urgeova L. Macek V. Klabnik A. Letavay P. Prochazka L. Vinanska D. Majercak I. Dominguez A.T. Pinilla J.M.G. Lama M.G. Villota J.N. Bonet L.A. Freire J.R.B. Perez G.P. Figal D.P. Diz F.W. Quintana A.G. Fernandez J.D. Cerezo J.G. Encinar J.B. Delgado F.G. Iborra P.L. Jurad F.J.C. Seller J. Kiatchoosakun S. Chirakarnjanakorn S. Sansanayudh N. Srimahachota S. Thongsri T. Mahavanakul W. Sahin T. Yigit Z. Melek M. Akin M. Cavusoglu Y. Koc M. Ozcan I.T. Turgut O.O. Yilmaz M.B. Altay H. Muderrisoglu H. Badak O. Tekten T. Oguzhan A. Kucuk M. Mahmood S. Dewhurst M.J. Asamoah-Owusu N.J. Clifford P. Takhar A. Hayes C. Moriarty A. Witte K. Cooke J. Haas D. Portnay E. Feitell S. Brown C.S. Hattler B. Fail P. Haddad T. Rama B. Kapoor N. Aslam S. Peters M. Sanchez E. Vijayasekaran S. Lupovitch S.D. Jonsson O. Schmalfuss C. Jain A. Mentzer G. Lepor N. Mignone J. Drummond W. Soverow J. Gaggin H. Garver R.I. Martinez-Castrillon M. Jaffrani N. Harris B.D. Bernstein M. Sizemore B.C. Wells T. Schwartz A.C. Alhaddad M. White A. Dargie H. Komajda M. Foley R. Francis G. Pocock S. Kaplan A.P. Brown N. Zuraw B. Busse P.J. Effect of sacubitril/valsartan vs standard medical therapies on plasma NT-proBNP concentration and submaximal exercise capacity in patients with heart failure and preserved ejection fraction: The PARALLAX randomized clinical trial. JAMA 2021 326 19 1919 1929 10.1001/jama.2021.18463 34783839
    [Google Scholar]
  24. Mentz R.J. Ward J.H. Hernandez A.F. Lepage S. Morrow D.A. Sarwat S. Sharma K. Starling R.C. Velazquez E.J. Williamson K.M. Desai A.S. Zieroth S. Solomon S.D. Braunwald E. Angiotensin-neprilysin inhibition in patients with mildly reduced or preserved ejection fraction and worsening heart failure. J. Am. Coll. Cardiol. 2023 82 1 1 12 10.1016/j.jacc.2023.04.019 37212758
    [Google Scholar]
  25. Solomon S.D. Rizkala A.R. Gong J. Wang W. Anand I.S. Ge J. Lam C.S.P. Maggioni A.P. Martinez F. Packer M. Pfeffer M.A. Pieske B. Redfield M.M. Rouleau J.L. Van Veldhuisen D.J. Zannad F. Zile M.R. Desai A.S. Shi V.C. Lefkowitz M.P. McMurray J.J.V. Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: Rationale and design of the PARAGON-HF trial. JACC Heart Fail. 2017 5 7 471 482 10.1016/j.jchf.2017.04.013 28662936
    [Google Scholar]
  26. Kommu S. Berg R.L. The efficacy and safety of sacubitril/valsartan compared to valsartan in patients with heart failure and mildly reduced and preserved ejection fractions: A systematic review and meta-analysis of randomized controlled trials. J. Clin. Med. 2024 13 6 1572 10.3390/jcm13061572 38541798
    [Google Scholar]
  27. Ponikowski P. Voors A.A. Anker S.D. Bueno H. Cleland J.G.F. Coats A.J.S. Falk V. González-Juanatey J.R. Harjola V.P. Jankowska E.A. Jessup M. Linde C. Nihoyannopoulos P. Parissis J.T. Pieske B. Riley J.P. Rosano G.M.C. Ruilope L.M. Ruschitzka F. Rutten F.H. van der Meer P. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2016 37 27 2129 2200 10.1093/eurheartj/ehw128 27206819
    [Google Scholar]
  28. Mantegazza V. Volpato V. Mapelli M. Sassi V. Salvioni E. Mattavelli I. Tamborini G. Agostoni P. Pepi M. Cardiac reverse remodelling by 2D and 3D echocardiography in heart failure patients treated with sacubitril/valsartan. Diagnostics 2021 11 10 1845 10.3390/diagnostics11101845 34679543
    [Google Scholar]
  29. Raphael D.M. Liu Z. Jin Z. Cui X. Han D. He W. Shangguan J. Shen D. Effects of sacubitril/valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease. Curr. Med. Res. Opin. 2021 37 7 1071 1078 10.1080/03007995.2021.1908243 33764230
    [Google Scholar]
  30. Zheng A. Adam R. Peebles C. Harden S. Shambrook J. Abbas A. Vedwan K. Adam G. Haydock P. Cowburn P. Young C. Long J. Walkden M. Smith S. Greenwood E. Olden P. Flett A. Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: The ENVI study. Open Heart 2024 11 2 e002933 10.1136/openhrt‑2024‑002933 39622578
    [Google Scholar]
  31. Mentz R.J. Ward J.H. Hernandez A.F. Lepage S. Morrow D.A. Sarwat S. Sharma K. Solomon S.D. Starling R.C. Velazquez E.J. Williamson K. Zieroth S. Braunwald E. Rationale, design and baseline characteristics of the PARAGLIDE-HF trial: sacubitril/valsartan vs valsartan in HFmrEF and HFpEF with a worsening heart failure event. J. Card. Fail. 2023 29 6 922 930 10.1016/j.cardfail.2023.02.001 36796671
    [Google Scholar]
  32. Schiller N.B. Shah P.M. Crawford M. DeMaria A. Devereux R. Feigenbaum H. Gutgesell H. Reichek N. Sahn D. Schnittger I. Silverman N.H. Tajik A.J. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J. Am. Soc. Echocardiogr. 1989 2 5 358 367 10.1016/S0894‑7317(89)80014‑8 2698218
    [Google Scholar]
  33. Nagueh S.F. Smiseth O.A. Appleton C.P. Byrd B.F. Dokainish H. Edvardsen T. Flachskampf F.A. Gillebert T.C. Klein A.L. Lancellotti P. Marino P. Oh J.K. Alexandru Popescu B. Waggoner A.D. 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. Eur. Heart J. Cardiovasc. Imaging 2016 17 12 1321 1360 10.1093/ehjci/jew082 27422899
    [Google Scholar]
  34. Rudski L.G. Lai W.W. Afilalo J. Hua L. Handschumacher M.D. Chandrasekaran K. Solomon S.D. Louie E.K. Schiller N.B. Guidelines for the echocardiographic assessment of the right heart in adults: A report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J. Am. Soc. Echocardiogr. 2010 23 7 685 713 10.1016/j.echo.2010.05.010 20620859
    [Google Scholar]
  35. Ahmeti A. Henein M.Y. Ibrahimi P. Elezi S. Haliti E. Poniku A. Batalli A. Bajraktari G. Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF. BMC Cardiovasc. Disord. 2017 17 1 268 10.1186/s12872‑017‑0705‑0 29041912
    [Google Scholar]
  36. Green C.P. Porter C.B. Bresnahan D.R. Spertus J.A. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: A new health status measure for heart failure. J. Am. Coll. Cardiol. 2000 35 5 1245 1255 10.1016/S0735‑1097(00)00531‑3 10758967
    [Google Scholar]
  37. Mogensen U.M. Gong J. Jhund P.S. Shen L. Køber L. Desai A.S. Lefkowitz M.P. Packer M. Rouleau J.L. Solomon S.D. Claggett B.L. Swedberg K. Zile M.R. Mueller-Velten G. McMurray J.J.V. Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF). Eur. J. Heart Fail. 2018 20 4 760 768 10.1002/ejhf.1139 29431251
    [Google Scholar]
  38. Peng W. Li X. Lin Y. Application and evaluation of sacubitril/valsartan in patients with cardiac insufficiency during perioperative period of cardiac surgery. Exp. Ther. Med. 2022 24 2 504 10.3892/etm.2022.11431 35837036
    [Google Scholar]
  39. Gubelli S. Caivano M. Case of a patient with heart failure, dilated cardiomyopathy and atrial fibrillation treated with sacubitril/valsartan. Curr. Med. Res. Opin. 2019 35 sup3 19 22 10.1080/03007995.2019.1598703 30895821
    [Google Scholar]
  40. House A.A. Wanner C. Sarnak M.J. Piña I.L. McIntyre C.W. Komenda P. Kasiske B.L. Deswal A. deFilippi C.R. Cleland J.G.F. Anker S.D. Herzog C.A. Cheung M. Wheeler D.C. Winkelmayer W.C. McCullough P.A. Abu-Alfa A.K. Amann K. Aonuma K. Appel L.J. Baigent C. Bakris G.L. Banerjee D. Boletis J.N. Bozkurt B. Butler J. Chan C.T. Costanzo M.R. Dubin R.F. Filippatos G. Gikonyo B.M. Gikonyo D.K. Hajjar R.J. Iseki K. Ishii H. Knoll G.A. Lenihan C.R. Lentine K.L. Lerma E.V. Macedo E. Mark P.B. Noiri E. Palazzuoli A. Pecoits-Filho R. Pitt B. Rigatto C. Rossignol P. Setoguchi S. Sood M.M. Störk S. Suri R.S. Szummer K. Tang S.C.W. Tangri N. Thompson A. Vijayaraghavan K. Walsh M. Wang A.Y-M. Weir M.R. Heart failure in chronic kidney disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019 95 6 1304 1317 10.1016/j.kint.2019.02.022 31053387
    [Google Scholar]
  41. von Lueder T.G. Wang B.H. Kompa A.R. Huang L. Webb R. Jordaan P. Atar D. Krum H. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ. Heart Fail. 2015 8 1 71 78 10.1161/CIRCHEARTFAILURE.114.001785 25362207
    [Google Scholar]
  42. Januzzi J.L. Prescott M.F. Butler J. Felker G.M. Maisel A.S. McCague K. Camacho A. Piña I.L. Rocha R.A. Shah A.M. Williamson K.M. Solomon S.D. 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 1085 1095 10.1001/jama.2019.12821 31475295
    [Google Scholar]
  43. Wang Y. Zhou R. Lu C. Chen Q. Xu T. Li D. Effects of the angiotensin‐receptor neprilysin inhibitor on cardiac reverse remodeling: Meta‐analysis. J. Am. Heart Assoc. 2019 8 13 e012272 10.1161/JAHA.119.012272 31240976
    [Google Scholar]
  44. McMurray J.J.V. Neprilysin inhibition to treat heart failure: A tale of science, serendipity, and second chances. Eur. J. Heart Fail. 2015 17 3 242 247 10.1002/ejhf.250 25756942
    [Google Scholar]
  45. Goldsmith S.R. Udelson J.E. Gheorghiade M. Dual vasopressin V1a/V2 antagonism: The next step in neurohormonal modulation in patients with heart failure? J. Card. Fail. 2018 24 2 112 114 10.1016/j.cardfail.2017.12.011 29329950
    [Google Scholar]
  46. Gori M. Volterrani M. Piepoli M. Senni M. Angiotensin receptor–neprilysin inhibitor (ARNi): Clinical studies on a new class of drugs. Int. J. Cardiol. 2017 226 136 140 10.1016/j.ijcard.2016.06.083 27378659
    [Google Scholar]
  47. Cao Z. Jia Y. Zhu B. BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both clinical and forensic medicine. Int. J. Mol. Sci. 2019 20 8 1820 10.3390/ijms20081820 31013779
    [Google Scholar]
  48. Humayra S. Yahya N. Ning C.J. Mohd Raffali M.A.A.F. Mir I.A. Mohamed A.L. Abdul Manan H. Clinical significance of NT-proBNP as a predictive biomarker of depressive symptoms in cardiac patients. Front. Cardiovasc. Med. 2025 12 1439520 10.3389/fcvm.2025.1439520 40236255
    [Google Scholar]
  49. Mouzarou A. Hadjigeorgiou N. Melanarkiti D. Plakomyti T.E. The role of NT-proBNP levels in the diagnosis of hypertensive heart disease. Diagnostics 2025 15 1 113 10.3390/diagnostics15010113 39795641
    [Google Scholar]
  50. Septiade H.D. Sjamsiah S. Yogiarto M. Cardiac stress marker NT-proBNP as an indicator of changes in cardiac function post percutaneous coronary intervention. Folia Med. Indones 2015 51 1 16 21
    [Google Scholar]
  51. Mapelli M. Mattavelli I. Salvioni E. Bonomi A. Capra N. Palermo P. Banfi C. Paolillo S. Biondi M.L. Agostoni P. Looking into the kinetics of NT-proBNP and sST2 changes in patients with heart failure treated with sacubitril/valsartan: A hint to different therapeutic pathways. Drugs R D. 2023 23 4 397 402 10.1007/s40268‑023‑00438‑2 37702906
    [Google Scholar]
  52. Savarese G. Hage C. Orsini N. Dahlström U. Perrone-Filardi P. Rosano G.M.C. Lund L.H. Reductions in N-terminal pro-brain natriuretic peptide levels are associated with lower mortality and heart failure hospitalization rates in patients with heart failure with mid-range and preserved ejection fraction. Circ. Heart Fail. 2016 9 11 e003105 10.1161/CIRCHEARTFAILURE.116.003105 28029640
    [Google Scholar]
  53. Robles Mezcua A. Sacubitril/valsartan treatment: Effect on left ventricular remodelling and fibrosis assessed by novel heart failure biomarkers. Eur Heart J. 2022 43 Supplement_2 ehac544.824 10.1093/eurheartj/ehac544.824
    [Google Scholar]
  54. Plata-Mosquera C.A. Bernal-Tórres W. Herrera-Escandón Á.A. Uribe-Posso L.P. Rodríguez-Casanova Á.M. Casanova-Valderrama M.E. Vivas-Mayor M. Puerta-Mesa A.C. Martínez-Aristizabal J. Sacubitril/valsartan reduces levels of procollagen types I and III and correlates with reverse cardiac remodeling. REC: CardioClinics 2021 56 1 14 21 10.1016/j.rccl.2020.06.002
    [Google Scholar]
  55. Januzzi J.L. Butler J. Fombu E. Maisel A. McCague K. Piña I.L. Prescott M.F. Riebman J.B. Solomon S. Rationale and methods of the prospective study of biomarkers, symptom improvement, and ventricular remodeling during sacubitril/valsartan therapy for heart failure (PROVE-HF). Am. Heart J. 2018 199 130 136 10.1016/j.ahj.2017.12.021 29754651
    [Google Scholar]
  56. McMurray J.J.V. Packer M. Desai A.S. Gong J. Lefkowitz M.P. Rizkala A.R. Rouleau J. Shi V.C. Solomon S.D. Swedberg K. Zile M.R. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: Rationale for and design of the prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF). Eur. J. Heart Fail. 2013 15 9 1062 1073 10.1093/eurjhf/hft052 23563576
    [Google Scholar]
  57. Moon M.G. Hwang I.C. Choi W. Cho G.Y. Yoon Y.E. Park J.B. Lee S.P. Kim H.K. Kim Y.J. Reverse remodelling by sacubitril/valsartan predicts the prognosis in heart failure with reduced ejection fraction. ESC Heart Fail. 2021 8 3 2058 2069 10.1002/ehf2.13285 33682334
    [Google Scholar]
  58. Landolfo M. Piani F. Esposti D.D. Cosentino E. Bacchelli S. Dormi A. Borghi C. Effects of sacubitril valsartan on clinical and echocardiographic parameters of outpatients with heart failure and reduced ejection fraction. Int. J. Cardiol. Heart Vasc. 2020 31 100656 10.1016/j.ijcha.2020.100656 33134479
    [Google Scholar]
  59. Castrichini M. Manca P. Nuzzi V. Barbati G. De Luca A. Korcova R. Stolfo D. Di Lenarda A. Merlo M. Sinagra G. Sacubitril/valsartan induces global cardiac reverse remodeling in long-lasting heart failure with reduced ejection fraction: Standard and advanced echocardiographic evidences. J. Clin. Med. 2020 9 4 906 10.3390/jcm9040906 32218231
    [Google Scholar]
  60. Piña I.L. Camacho A. Ibrahim N.E. Felker G.M. Butler J. Maisel A.S. Prescott M.F. Williamson K.M. Claggett B.L. Desai A.S. Solomon S.D. Januzzi J.L. Improvement of health status following initiation of sacubitril/valsartan in heart failure and reduced ejection fraction. JACC Heart Fail. 2021 9 1 42 51 10.1016/j.jchf.2020.09.012 33189630
    [Google Scholar]
  61. Martens P. Beliën H. Dupont M. Mullens W. Insights into implementation of sacubitril/valsartan into clinical practice. ESC Heart Fail. 2018 5 3 275 283 10.1002/ehf2.12258 29464879
    [Google Scholar]
  62. Luo N. Fonarow G.C. Lippmann S.J. Mi X. Heidenreich P.A. Yancy C.W. Greiner M.A. Hammill B.G. Hardy N.C. Turner S.J. Laskey W.K. Curtis L.H. Hernandez A.F. Mentz R.J. O’Brien E.C. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: Insights from Get With the Guidelines–Heart Failure (GWTG-HF). JACC Heart Fail. 2017 5 4 305 309 10.1016/j.jchf.2016.12.018 28359417
    [Google Scholar]
  63. DeVore A.D. Thomas L. Albert N.M. Butler J. Hernandez A.F. Patterson J.H. Spertus J.A. Williams F.B. Turner S.J. Chan W.W. Duffy C.I. McCague K. Mi X. Fonarow G.C. Change the management of patients with heart failure: Rationale and design of the CHAMP-HF registry. Am. Heart J. 2017 189 177 183 10.1016/j.ahj.2017.04.010 28625374
    [Google Scholar]
  64. Chernyavsky P. Surgical remodeling of the left ventricle in patients with post-infarction dilation and heart failure. Russ Sklifosovsky J. Emerg. Med. Care 2022 11 1 50 58
    [Google Scholar]
  65. Kuchynka P. Long-term clinical outcomes and left ventricular reverse remodeling in recently diagnosed unexplained dilated cardiomyopathy. ESC Heart Fail. 2024 11 2 10.1002/ehf2.14643
    [Google Scholar]
  66. Wang S. Left ventricular reverse remodeling after revascularization and its predictive role for survival. medRxiv 2023 2023.10 10.1101/2023.10.31.23297881
    [Google Scholar]
  67. Zhou X. Zhu H. Zheng Y. Tan X. Tong X. A systematic review and meta-analysis of sacubitril-valsartan in the treatment of ventricular remodeling in patients with heart failure after acute myocardial infarction. Front. Cardiovasc. Med. 2022 9 953948 10.3389/fcvm.2022.953948 36304540
    [Google Scholar]
  68. Zhang H. Huetteman A.T. Reyes E.A. Appelbaum J.S. Effects of sacubitril–valsartan in patients with various types of heart failure: A meta-analysis. J. Cardiovasc. Pharmacol. 2023 81 6 434 444 10.1097/FJC.0000000000001421 37000983
    [Google Scholar]
  69. Valli F. Bursi F. Santangelo G. Toriello F. Faggiano A. Rusconi I. Vella A.M. Carugo S. Guazzi M. Long-term effects of sacubitril-valsartan on cardiac remodeling: A parallel echocardiographic study of left and right heart adaptive response. J. Clin. Med. 2023 12 7 2659 10.3390/jcm12072659 37048742
    [Google Scholar]
  70. Hernandez A. Effects of sacubitril valsartan on renal function in adults with heart failure: A systematic review and meta analysis of randomised controlled trials. Eur Heart J. 2022 43 Supplement_2 ehac544.958 10.1093/eurheartj/ehac544.958
    [Google Scholar]
  71. Jain A. Meyur S. Wadhwa L. Singh K. Sharma R. Panchal I. Varrassi G. Effects of angiotensin receptor-neprilysin inhibitors versus enalapril or valsartan on patients with heart failure: A systematic review and meta-analysis. Cureus 2023 15 7 e41566 10.7759/cureus.41566 37554618
    [Google Scholar]
  72. Wu Z. Cui W. Li G. Li L. Bian Y. Effect of sacubitril and valsartan combined with conventional therapy on patients with heart failure. Trop. J. Pharm. Res. 2024 23 9 1541 1547 10.4314/tjpr.v23i9.18
    [Google Scholar]
  73. Romano G. Vitale G. Ajello L. Agnese V. Bellavia D. Caccamo G. Corrado E. Di Gesaro G. Falletta C. La Franca E. Minà C. Storniolo S.A. Sarullo F.M. Clemenza F. The effects of sacubitril/valsartan on clinical, biochemical and echocardiographic parameters in patients with heart failure with reduced ejection fraction: The “hemodynamic recovery”. J. Clin. Med. 2019 8 12 2165 10.3390/jcm8122165 31817815
    [Google Scholar]
  74. Ferreira J.P. Mogensen U.M. Jhund P.S. Desai A.S. Rouleau J.L. Zile M.R. Rossignol P. Zannad F. Packer M. Solomon S.D. McMurray J.J.V. Serum potassium in the PARADIGM‐HF trial. Eur. J. Heart Fail. 2020 22 11 2056 2064 10.1002/ejhf.1987 32809261
    [Google Scholar]
  75. Nielsen E.E. Feinberg J.B. Bu F.L. Hecht Olsen M. Raymond I. Steensgaard-Hansen F. Jakobsen J.C. Beneficial and harmful effects of sacubitril/valsartan in patients with heart failure: A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Open Heart 2020 7 2 e001294 10.1136/openhrt‑2020‑001294 33257469
    [Google Scholar]
  76. Moraña-Fernández S. Vázquez-Abuín X. Aragón-Herrera A. Anido-Varela L. García-Seara J. Otero-García Ó. Rodríguez-Penas D. Campos-Toimil M. Otero-Santiago M. Rodrigues A. Gonçalves A. Pereira Morais J. Alves I.N. Sousa-Mendes C. Falcão-Pires I. González-Juanatey J.R. Feijóo-Bandín S. Lago F. Cardiometabolic effects of sacubitril/valsartan in a rat model of heart failure with preserved ejection fraction. Biochem. Pharmacol. 2024 230 Pt 1 116571 10.1016/j.bcp.2024.116571 39424202
    [Google Scholar]
  77. Suzuki K. Claggett B. Minamisawa M. Packer M. Zile M.R. Rouleau J. Swedberg K. Lefkowitz M. Shi V. McMurray J.J.V. Zucker S.D. Solomon S.D. Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction. Eur. J. Heart Fail. 2020 22 9 1662 1671 10.1002/ejhf.1853 32407608
    [Google Scholar]
  78. Kanaoka K. Nasu T. Kikuchi A. Ijichi T. Shibata T. Kida K. Kagiyama N. Fujimoto W. Ishii S. Iwanaga Y. Miyamoto Y. Matsumoto S. Risk stratification by renal function and NYHA class in patients with hypotension initiated on sacubitril/valsartan: A retrospective cohort study from 17 centres in Japan. Open Heart 2024 11 2 e002764 10.1136/openhrt‑2024‑002764 39433425
    [Google Scholar]
  79. Sadłowski B. Bieganek P. Łukaszewicz S. Pawłowski P. Rybak J. Kordialik J. Koćwin J. Sarnacka S. Tokarski M. Banasiak A. Sacubitril with valsartan, a modern pharmacotherapy in heart failure - A literature review. Quality in Sport. 2024 17 53117 53117 10.12775/QS.2024.17.53117
    [Google Scholar]
  80. Lin D.S.H. Chao Y.T. Chuang S.L. Lee J.K. Lin T.T. Lin L.C. Huang K.C. Hwang J.J. Effects of sacubitril/valsartan on survival in patients with heart failure and significant valvular heart disease. Clin. Pharmacol. Ther. 2025 117 1 143 152 10.1002/cpt.3417 39148369
    [Google Scholar]
  81. Yamaguchi N. Kusunose K. Hirata Y. Nishio S. Takahashi T. Saijo Y. Kadota M. Ise T. Yamaguchi K. Yagi S. Yamada H. Soeki T. Wakatsuki T. Sata M. Abstract 14279: Improved pressure-flow relationship with sacubitril/valsartan: A 6-min walk stress echocardiographic study. Circulation 2023 148 A14279 A14279 (Suppl. 1) 10.1161/circ.148.suppl_1.14279
    [Google Scholar]
  82. Fröhlich H. Frey N. Estler B. Mäck M. Schlegel P. Beckendorf J. Frankenstein L. Täger T. Haemodynamic effects of sacubitril/valsartan initiation in outpatients with chronic heart failure. Am. J. Cardiovasc. Drugs 2022 22 6 695 704 10.1007/s40256‑022‑00549‑2 36136241
    [Google Scholar]
  83. Nederend M. Kiès P. Regeer M.V. Vliegen H.W. Mertens B.J.A. Robbers-Visser D. Bouma B.J. Tops L.F. Schalij M.J. Jongbloed M.R.M. Egorova A.D. Tolerability and beneficial effects of sacubitril/valsartan on systemic right ventricular failure. Heart 2023 109 20 1525 1532 10.1136/heartjnl‑2022‑322332 37169551
    [Google Scholar]
  84. Nurzhanova M. Musagaliyeva A. Zhakypova R. Senkibayeva D. Rakisheva A. Use of sacubitril/valsartan early after CABG. Open Heart 2024 11 1 e002492 10.1136/openhrt‑2023‑002492 38238027
    [Google Scholar]
  85. Fusco F. Effects of sacubitril/valsartan in patients with a systemic right ventricle. Eur Heart J. 2022 43 Supplement_2 ehac544.1849 10.1093/eurheartj/ehac544.1849
    [Google Scholar]
  86. Huang Y. Zhang Y. Ma L. Zhou H. Fang C. Chen C. Adverse events of sacubitril/valsartan: A meta-analysis of randomized controlled trials. J. Cardiovasc. Pharmacol. 2021 78 2 202 210 10.1097/FJC.0000000000001049 33929386
    [Google Scholar]
  87. Kim Y.S. Brar S. D’Albo N. Dey A. Shah S. Ganatra S. Dani S.S. Five years of sacubitril/valsartan—A safety analysis of randomized clinical trials and real-world pharmacovigilance. Cardiovasc. Drugs Ther. 2022 36 5 915 924 10.1007/s10557‑021‑07210‑1 34125356
    [Google Scholar]
  88. Chen Z. Li J. Zhou Y. Qiu Q. Yan D. Peng G. Xu Y. Ye Y. Shen Y. Comparison of the pharmacovigilance signals of cardiac and renal adverse events associated with sacubitril/valsartan and valsartan alone based on the FAERS database. Expert Opin. Drug Saf. 2025 24 4 445 452 10.1080/14740338.2024.2436100 39625739
    [Google Scholar]
  89. Mann D.L. Givertz M.M. Vader J.M. Starling R.C. Shah P. McNulty S.E. Anstrom K.J. Margulies K.B. Kiernan M.S. Mahr C. Gupta D. Redfield M.M. Lala A. Lewis G.D. DeVore A.D. Desvigne-Nickens P. Hernandez A.F. Braunwald E. Mohammed S.F. Birru H. Aboye E. Lam P.H. Escobar N. Fink M. Cappola T.P. Sheaffer W. Reilly B. Ferree J. Ravichandran A.K. Ciezkowski G. Herrera G. Mehta H.S. DeLucca R. Doddamani S. Kanwar M. Thomas B. Machen L. Kim J. Christina A. Lampert B.C. Fontenelle C. Eiswirth C.C. Williams J. Rock D. Egnaczyk G.F. Rentas-Sherman E. Barr D. Bhimaraj A. Damato A. Calayo C. Herre J.M. Lindenfeld J. Carroll A. Gordon M. Keebler M.E. Setliff B. Gulati S.K. Winkler K. Curtin L. Ohmart C. Halvorson J. Mudd J.O. Camacho S.A. Palardy M. Shah N. Picardi K. Krishnamoorthy A. Maximin A. Horstmanshof D.A. Seiler B. Xu Z.J. Mersola S. Kransdorf E.P. Tang W. Fonk T. Gorodeski E.Z. Oliveira G.H. Semenec T. Norton N. Nichols J. Leo P. Dunlap M.E. Felker G.M. Taylor L. Sheehan M. Levine S. Cocca-Spofford D. Brooks L. Cunningham T. Acker N. Milbrandt S. Gatzke J. Davila-Roman V.G. Dirks A. Bult K. Weber E. Lesko M. Mikhalkova D. Fitzgerald K. Whellan D.J. Wever-Pinzon O. Gutierrez J. Goldsborough Y. Gilotra N.A. Caikauskaite I. Skopicki H.A. Huggins G.S. Yuen N. Haynes A. Katie C. Snell G. Smith A.L. Walker B. Johnson J. Henderson S. Pauwaa S. Bhat G. Gagliardi A. Effect of treatment with sacubitril/valsartan in patients with advanced heart failure and reduced ejection fraction: A randomized clinical trial. JAMA Cardiol. 2022 7 1 17 25 10.1001/jamacardio.2021.4567 34730769
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: HFrEF ; Heart failure ; sacubitril ; valsartan ; ventricular remodeling
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