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Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure

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Abstract

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end‐diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg.

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References

  1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, Investigators Committees (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993–1004

    Article  PubMed  Google Scholar 

  2. Solomon SD, Vaduganathan M, Brian LC, Packer M, Zile M, Swedberg K, Rouleau J, Marc AP, Desai A, Lund LH, Kober L, Anand I, Sweitzer N, Linssen G, Merkely B, Luis Arango J, Vinereanu D, Chen CH, Senni M, Sibulo A, Boytsov S, Shi V, Rizkala A, Lefkowitz M, McMurray JJV (2020) Sacubitril/valsartan across the spectrum of ejection fraction in heart failure. Circulation 141:352–361

    Article  PubMed  Google Scholar 

  3. Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A (2016) Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail 18:1193–1202

    Article  CAS  PubMed  Google Scholar 

  4. Vardeny O, Claggett B, Packer M, Zile MR, Rouleau J, Swedberg K, Teerlink JR, Desai AS, Lefkowitz M, Shi V, McMurray JJ, Solomon SD (2016) Prospective comparison of AwAtDIoGM, morbidity in heart failure I. Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial. Eur J Heart Fail 18:1228–1234

    Article  CAS  PubMed  Google Scholar 

  5. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP, Investigators Committees (2019) Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 381:1609–1620

    Article  CAS  PubMed  Google Scholar 

  6. Pieske B, Wachter R, Shah SJ, Baldridge A, Szeczoedy P, Ibram G, Shi V, Zhao Z, Cowie MR, Investigators Committee (2021) 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 326:1919–1929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Januzzi JL Jr, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, Camacho A, Pina IL, Rocha RA, Shah AM, Williamson KM, Solomon SD, Investigators (2019) 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 322:1085–1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Corrado E, Dattilo G, Coppola G, Morabito C, Bonni E, Zappia L, Novo G, de Gregorio C (2022) Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients. Eur J Clin Pharmacol 78:19–25

    Article  CAS  PubMed  Google Scholar 

  9. Schmieder RE, Wagner F, Mayr M, Delles C, Ott C, Keicher C, Hrabak-Paar M, Heye T, Aichner S, Khder Y, Yates D, Albrecht D, Langenickel T, Freyhardt P, Janka R, Bremerich J (2017) The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study. Eur Heart J 38:3308–3317

    Article  CAS  PubMed  Google Scholar 

  10. Guerra F, Ammendola E, Ziacchi M, Aspromonte V, Pellegrino PL, Del Giorno G, Dell’Era G, Pimpini L, Santoro F, Floris R, Stronati G, Nigro G, Paolisso P, Guido A, Maglia G, Brunetti ND, Carbone A, Gravellone M, Antonicelli R, Cannone M, Accogli M, Dello Russo A, Palmisano P (2021) Effect of sacubitril/valsartan on left ventricular ejection fraction and on the potential indication for implantable cardioverter defibrillator in primary prevention: the SAVE-ICD study. Eur J Clin Pharmacol 77:1835–1842

    Article  CAS  PubMed  Google Scholar 

  11. Desai AS, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Chen F, Gong J, Rizkala AR, Brahimi A, Claggett B, Finn PV, Hartley LH, Liu J, Lefkowitz M, Shi V, Zile MR, Solomon SD (2015) Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J 36:1990–1997

    Article  CAS  PubMed  Google Scholar 

  12. Tsutsui H, Momomura SI, Saito Y, Ito H, Yamamoto K, Sakata Y, Desai AS, Ohishi T, Iimori T, Kitamura T, Guo W, Investigators (2021) Efficacy and safety of sacubitril/valsartan in japanese patients with chronic heart failure and reduced ejection fraction-results from the PARALLEL-HF study. Circ J 85:584–594

    Article  CAS  PubMed  Google Scholar 

  13. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation 145:e876–e894

    PubMed  Google Scholar 

  14. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, Group ESCSD (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42:3599–3726

    Article  CAS  PubMed  Google Scholar 

  15. Tsutsui H, Ide T, Ito H, Kihara Y, Kinugawa K, Kinugawa S, Makaya M, Murohara T, Node K, Saito Y, Sakata Y, Shimizu W, Yamamoto K, Bando Y, Iwasaki YK, Kinugasa Y, Mizote I, Nakagawa H, Oishi S, Okada A, Tanaka A, Akasaka T, Ono M, Kimura T, Kosaka S, Kosuge M, Momomura SI, Japanese Circulation S, The Japanese Heart Failure Society Joint Working (2021) JCS/JHFS 2021 guideline focused update on diagnosis and treatment of acute and chronic heart failure. Circ J 85:2252–2291

    Article  CAS  PubMed  Google Scholar 

  16. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American society of echocardiography and the European association of cardiovascular imaging. J Am Soc Echocardiogr 28(1–39):e14

    Google Scholar 

  17. Cohn JN, Tognoni G, Trial I VHF (2001) A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 345:1667–1675

    Article  CAS  PubMed  Google Scholar 

  18. Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K, Candesartan in Heart failure Assessment of Reduction in M, morbidity I, Committees (2004) Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation 110:2618–2626

    Article  CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Yu Nishihara, Makoto Nishimori, Koya Uemura, Shun Nagai, Saki Todo, Eri Oota, Susumu Odajima, Kimikazu Takeuchi, Yasushi Ichikawa, Masayuki Kintsu, Yuki Yamauchi, Hiroaki Shiraki, Kentaro Yamashita, Terunobu Fukuda, Eriko Hisamatsu, Ken-ichi Hirata & Hidekazu Tanaka

  2. Division of Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan

    Makoto Nishimori

  3. Division of Cardiology, National Hospital Organization Kobe Medical Center, Kobe, Japan

    Takuma Sawa & Masatoshi Shimizu

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  1. Yu Nishihara
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Correspondence to Hidekazu Tanaka.

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Conflict of interest

H.T. is a consultant for AstraZeneca plc, Ono Pharmaceutical Company, Limited. Pfizer Inc, Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, and Novartis International AG. H.O is a consultant for Abbott Vascular Japan and Terumo Co. K.H. has received research funding from Daiichi Sankyo Company, Limited, Actelion Pharmaceuticals Japan, Terumo Corporation, Abbott Vascular Japan, Otsuka Pharmaceutical Company, Limited, Kowa Company, Limited, Takeda Pharmaceutical Company Limited, Nihon Medi-Physics Company Limited, Novartis Pharma Company Limited, Bayer Company Limited, Biotronic Japan Company Limited, FUJIFILM Toyama Chemical Company Limited, Medtronic Japan Company Limited, Sysmex Company Limited. The remaining authors have no conflicts of interest to declare.

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Nishihara, Y., Nishimori, M., Sawa, T. et al. Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure. Heart Vessels 39, 95–104 (2024). https://doi.org/10.1007/s00380-023-02311-3

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