射血分数保留型心力衰竭的治疗进展
Treatment Progress of Heart Failure with Preserved Ejection Fraction
DOI: 10.12677/acrvm.2025.132002, PDF,   
作者: 王义涛:华北理工大学研究生院,河北 唐山;谷 剑:河北省人民医院心血管内科,河北 石家庄
关键词: 射血分数保留型心力衰竭(HFpEF)药物治疗合并症管理Heart Failure with Preserved Ejection Fraction (HFpEF) Pharmacotherapy Comorbidity Management
摘要: 射血分数保留型心力衰竭(HFpEF)是心力衰竭的一种亚型,定义为具有心衰的症状及体征,伴有左室射血分数(LVEF) ≥ 50%。近年来,HFpEF的流行病学特征发生显著变化,已成为心衰的主要类型,且患病率持续上升。尽管HFpEF患者的短期死亡率低于射血分数降低的心力衰竭(HFrEF),但其长期预后仍严峻,住院率与HFrEF相当,且非心血管死亡占比较高。目前,对HFpEF的病理生理机制研究尚未完全阐明,临床管理上缺乏特异性疗法。本文综述了HFpEF的治疗现状及当前针对其潜在治疗靶点的探索。药物治疗方面,钠–葡萄糖协同转运蛋白2抑制剂(SGLT2i)作为里程碑式突破,通过多重机制改善HFpEF症状及预后。盐皮质激素受体拮抗剂(MRA)、血管紧张素受体–脑啡肽酶抑制剂(ARNI)、血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂(ACEI/ARB)及β受体阻滞剂等药物的临床疗效存在显著异质性。此外,本文还讨论了HFpEF合并症的管理,包括肥胖、心房颤动、高血压、糖尿病、慢性肾病及阻塞性睡眠呼吸暂停等,并指出了未来研究方向,即从传统治疗模式向精准医学策略转型。
Abstract: Heart failure with preserved ejection fraction (HFpEF) is a subtype of heart failure defined by the presence of heart failure symptoms and signs, accompanied by a left ventricular ejection fraction (LVEF) ≥ 50%. In recent years, the epidemiological characteristics of HFpEF have undergone significant changes, making it the predominant type of heart failure, with a continuously rising prevalence. Although the short-term mortality of HFpEF patients is lower than that of heart failure with reduced ejection fraction (HFrEF), their long-term prognosis remains severe, with hospitalization rates comparable to HFrEF and a higher proportion of non-cardiovascular deaths. Currently, the pathophysiological mechanisms of HFpEF have not been fully elucidated, and specific therapies are lacking in clinical management. This paper reviews the current treatment status of HFpEF and the exploration of potential therapeutic targets. In terms of pharmacotherapy, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a milestone breakthrough, improving symptoms and prognosis in HFpEF through multiple mechanisms. The clinical efficacy of mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNI), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and β-blockers varies significantly. Additionally, this paper discusses the management of HFpEF comorbidities, including obesity, atrial fibrillation, hypertension, diabetes, chronic kidney disease, and obstructive sleep apnea, and points out future research directions, namely, the transition from traditional treatment models to precision medicine strategies.
文章引用:王义涛, 谷剑. 射血分数保留型心力衰竭的治疗进展[J]. 亚洲心脑血管病例研究, 2025, 13(2): 11-18. https://doi.org/10.12677/acrvm.2025.132002

参考文献

[1] 国家心血管病中心, 国家心血管病专家委员会心力衰竭专业委员会, 中国医师协会心力衰竭专业委员会, 等. 国家心力衰竭指南2023 [J]. 中华心力衰竭和心肌病杂志, 2023, 7(4): 215-311.
[2] Becher, P.M., Lund, L.H., Coats, A.J.S. and Savarese, G. (2022) An Update on Global Epidemiology in Heart Failure. European Heart Journal, 43, 3005-3007. [Google Scholar] [CrossRef] [PubMed]
[3] Gerber, Y., Weston, S.A., Redfield, M.M., Chamberlain, A.M., Manemann, S.M., Jiang, R., et al. (2015) A Contemporary Appraisal of the Heart Failure Epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Internal Medicine, 175, 996-1004. [Google Scholar] [CrossRef] [PubMed]
[4] Lee, D.S., Gona, P., Vasan, R.S., Larson, M.G., Benjamin, E.J., Wang, T.J., et al. (2009) Relation of Disease Pathogenesis and Risk Factors to Heart Failure with Preserved or Reduced Ejection Fraction. Circulation, 119, 3070-3077. [Google Scholar] [CrossRef] [PubMed]
[5] Heidenreich, P.A., Bozkurt, B., Aguilar, D., Allen, L.A., Byun, J.J., Colvin, M.M., et al. (2022) 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 145, e895-e1032. [Google Scholar] [CrossRef] [PubMed]
[6] Groenewegen, A., Rutten, F.H., Mosterd, A. and Hoes, A.W. (2020) Epidemiology of Heart Failure. European Journal of Heart Failure, 22, 1342-1356. [Google Scholar] [CrossRef] [PubMed]
[7] Dokainish, H., Teo, K., Zhu, J., et al. (2017) Global Mortality Variations in Patients with Heart Failure: Results from the International Congestive Heart Failure (INTER-CHF) Prospective Cohort Study. The Lancet Global Health, 5, e665-e672.
[8] Owan, T.E., Hodge, D.O., Herges, R.M., Jacobsen, S.J., Roger, V.L. and Redfield, M.M. (2006) Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction. New England Journal of Medicine, 355, 251-259. [Google Scholar] [CrossRef] [PubMed]
[9] Shiba, N., Nochioka, K., Miura, M., Kohno, H. and Shimokawa, H. (2011) Trend of Westernization of Etiology and Clinical Characteristics of Heart Failure Patients in Japan. Circulation Journal, 75, 823-833. [Google Scholar] [CrossRef] [PubMed]
[10] Borlaug, B.A. (2020) Evaluation and Management of Heart Failure with Preserved Ejection Fraction. Nature Reviews Cardiology, 17, 559-573. [Google Scholar] [CrossRef] [PubMed]
[11] ter Maaten, J.M., Damman, K., Verhaar, M.C., Paulus, W.J., Duncker, D.J., Cheng, C., et al. (2016) Connecting Heart Failure with Preserved Ejection Fraction and Renal Dysfunction: The Role of Endothelial Dysfunction and Inflammation. European Journal of Heart Failure, 18, 588-598. [Google Scholar] [CrossRef] [PubMed]
[12] Solomon, S.D., Rizkala, A.R., Lefkowitz, M.P., et al. (2018) Baseline Characteristics of Patients with Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial. Circulation: Heart Failure, 11, e4962.
[13] Verma, S., Rawat, S., Ho, K.L., Wagg, C.S., Zhang, L., Teoh, H., et al. (2018) Empagliflozin Increases Cardiac Energy Production in Diabetes. JACC: Basic to Translational Science, 3, 575-587. [Google Scholar] [CrossRef] [PubMed]
[14] Nassif, M.E., Qintar, M., Windsor, S.L., Jermyn, R., Shavelle, D.M., Tang, F., et al. (2021) Empagliflozin Effects on Pulmonary Artery Pressure in Patients with Heart Failure. Circulation, 143, 1673-1686. [Google Scholar] [CrossRef] [PubMed]
[15] Shah, S.J., Lam, C.S.P., Svedlund, S., Saraste, A., Hage, C., Tan, R., et al. (2018) Prevalence and Correlates of Coronary Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: PROMIS-HFpEF. European Heart Journal, 39, 3439-3450. [Google Scholar] [CrossRef] [PubMed]
[16] Abraham, W.T., Lindenfeld, J., Ponikowski, P., Agostoni, P., Butler, J., Desai, A.S., et al. (2020) Effect of Empagliflozin on Exercise Ability and Symptoms in Heart Failure Patients with Reduced and Preserved Ejection Fraction, with and without Type 2 Diabetes. European Heart Journal, 42, 700-710. [Google Scholar] [CrossRef] [PubMed]
[17] McDonagh, T.A., Metra, M., Adamo, M., Gardner, R.S., Baumbach, A., Böhm, M., et al. (2022) 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. European Journal of Heart Failure, 24, 4-131. [Google Scholar] [CrossRef] [PubMed]
[18] Pfeffer, M.A., Claggett, B., Assmann, S.F., Boineau, R., Anand, I.S., Clausell, N., 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] [CrossRef] [PubMed]
[19] Hahn, V.S., Yanek, L.R., Vaishnav, J., Ying, W., Vaidya, D., Lee, Y.Z.J., et al. (2020) Endomyocardial Biopsy Characterization of Heart Failure with Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis. JACC: Heart Failure, 8, 712-724. [Google Scholar] [CrossRef] [PubMed]
[20] Chyou, J.Y., Qin, H., Butler, J., Voors, A.A. and Lam, C.S.P. (2024) Sex-Related Similarities and Differences in Responses to Heart Failure Therapies. Nature Reviews Cardiology, 21, 498-516. [Google Scholar] [CrossRef] [PubMed]
[21] Mc Causland, F.R., Lefkowitz, M.P., Claggett, B., Anavekar, N.S., Senni, M., Gori, M., et al. (2020) Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure with Preserved Ejection Fraction. Circulation, 142, 1236-1245. [Google Scholar] [CrossRef] [PubMed]
[22] Pfeffer, M.A., Swedberg, K., Granger, C.B., Held, P., McMurray, J.J., Michelson, E.L., et al. (2003) Effects of Candesartan on Mortality and Morbidity in Patients with Chronic Heart Failure: The Charm-Overall Programme. The Lancet, 362, 759-766. [Google Scholar] [CrossRef] [PubMed]
[23] Shah, R.V., Desai, A.S. and Givertz, M.M. (2010) The Effect of Renin-Angiotensin System Inhibitors on Mortality and Heart Failure Hospitalization in Patients with Heart Failure and Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. Journal of Cardiac Failure, 16, 260-267. [Google Scholar] [CrossRef] [PubMed]
[24] Katz, D.H., Beussink, L., Sauer, A.J., Freed, B.H., Burke, M.A. and Shah, S.J. (2013) Prevalence, Clinical Characteristics, and Outcomes Associated with Eccentric versus Concentric Left Ventricular Hypertrophy in Heart Failure with Preserved Ejection Fraction. The American Journal of Cardiology, 112, 1158-1164. [Google Scholar] [CrossRef] [PubMed]
[25] Cleland, J.G.F., Bunting, K.V., Flather, M.D., Altman, D.G., Holmes, J., Coats, A.J.S., et al. (2017) Beta-Blockers for Heart Failure with Reduced, Mid-Range, and Preserved Ejection Fraction: An Individual Patient-Level Analysis of Double-Blind Randomized Trials. European Heart Journal, 39, 26-35. [Google Scholar] [CrossRef] [PubMed]
[26] Palau, P., de la Espriella, R., Seller, J., Santas, E., Domínguez, E., Bodí, V., et al. (2024) β-Blocker Withdrawal and Functional Capacity Improvement in Patients with Heart Failure with Preserved Ejection Fraction. JAMA Cardiology, 9, 392-396. [Google Scholar] [CrossRef] [PubMed]
[27] Aminian, A., Zajichek, A., Arterburn, D.E., Wolski, K.E., Brethauer, S.A., Schauer, P.R., et al. (2019) Association of Metabolic Surgery with Major Adverse Cardiovascular Outcomes in Patients with Type 2 Diabetes and Obesity. Journal of the American Medical Association, 322, 1271-1282. [Google Scholar] [CrossRef] [PubMed]
[28] Bilak, J.M., Alam, U., Miller, C.A., McCann, G.P., Arnold, J.R. and Kanagala, P. (2022) Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction: Pathophysiology, Assessment, Prevalence and Prognosis. Cardiac Failure Review, 8, e24. [Google Scholar] [CrossRef] [PubMed]
[29] Sugumar, H., Nanayakkara, S., Vizi, D., Wright, L., Chieng, D., Leet, A., et al. (2021) A Prospective Study Using Invasive Haemodynamic Measurements Following Catheter Ablation for AF and Early HFpEF: Stall AF-HFpEF. European Journal of Heart Failure, 23, 785-796. [Google Scholar] [CrossRef] [PubMed]
[30] Kotecha, D., Bunting, K.V., Gill, S.K., Mehta, S., Stanbury, M., Jones, J.C., et al. (2020) Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life. Journal of the American Medical Association, 324, 2497-2508. [Google Scholar] [CrossRef] [PubMed]
[31] McDonagh, T.A., Metra, M., Adamo, M., Gardner, R.S., Baumbach, A., Böhm, M., et al. (2024) 2023 Focused Update of the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. European Journal of Heart Failure, 26, 5-17. [Google Scholar] [CrossRef] [PubMed]
[32] Upadhya, B., Rocco, M., Lewis, C.E., Oparil, S., Lovato, L.C., Cushman, W.C., et al. (2017) Effect of Intensive Blood Pressure Treatment on Heart Failure Events in the Systolic Blood Pressure Reduction Intervention Trial. Circulation: Heart Failure, 10, e003613. [Google Scholar] [CrossRef] [PubMed]
[33] Borlaug, B.A., Lam, C.S.P., Roger, V.L., Rodeheffer, R.J. and Redfield, M.M. (2009) Contractility and Ventricular Systolic Stiffening in Hypertensive Heart Disease. Journal of the American College of Cardiology, 54, 410-418. [Google Scholar] [CrossRef] [PubMed]
[34] Packer, M., Lam, C.S.P., Lund, L.H., Maurer, M.S. and Borlaug, B.A. (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. European Journal of Heart Failure, 22, 1551-1567. [Google Scholar] [CrossRef] [PubMed]
[35] Liu, M., Fang, F. and Yu, C. (2015) Noncardiac Comorbidities in Heart Failure with Preserved Ejection Fraction—A Commonly Ignored Fact. Circulation Journal, 79, 954-959. [Google Scholar] [CrossRef] [PubMed]
[36] Deichl, A., Wachter, R. and Edelmann, F. (2022) Comorbidities in Heart Failure with Preserved Ejection Fraction. Herz, 47, 301-307. [Google Scholar] [CrossRef] [PubMed]
[37] Vaduganathan, M., Docherty, K.F., Claggett, B.L., Jhund, P.S., de Boer, R.A., Hernandez, A.F., et al. (2022) SGLT2 Inhibitors in Patients with Heart Failure: A Comprehensive Meta-Analysis of Five Randomized Controlled Trials. The Lancet, 400, 757-767. [Google Scholar] [CrossRef] [PubMed]
[38] Halabi, A., Sen, J., Huynh, Q. and Marwick, T.H. (2020) Metformin Treatment in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Regression Analysis. Cardiovascular Diabetology, 19, Article No. 124. [Google Scholar] [CrossRef] [PubMed]
[39] Patel, R.N., Sharma, A., Prasad, A. and Bansal, S. (2023) Heart Failure with Preserved Ejection Fraction with CKD: A Narrative Review of a Multispecialty Disorder. Kidney Medicine, 5, Article 100705. [Google Scholar] [CrossRef] [PubMed]
[40] Arikawa, T., Toyoda, S., Haruyama, A., Amano, H., Inami, S., Otani, N., et al. (2016) Impact of Obstructive Sleep Apnoea on Heart Failure with Preserved Ejection Fraction. Heart, Lung and Circulation, 25, 435-441. [Google Scholar] [CrossRef] [PubMed]
[41] O’Connor, C.M., Whellan, D.J., Fiuzat, M., Punjabi, N.M., Tasissa, G., Anstrom, K.J., et al. (2017) Cardiovascular Outcomes with Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure. Journal of the American College of Cardiology, 69, 1577-1587. [Google Scholar] [CrossRef] [PubMed]
[42] Pinna, G.D., Robbi, E., La Rovere, M.T., Taurino, A.E., Bruschi, C., Guazzotti, G., et al. (2015) Differential Impact of Body Position on the Severity of Disordered Breathing in Heart Failure Patients with Obstructive vs. Central Sleep Apnoea. European Journal of Heart Failure, 17, 1302-1309. [Google Scholar] [CrossRef] [PubMed]
[43] 张慧, 吕慧霞. 阻塞性睡眠呼吸暂停在心衰进展中的作用机制及其治疗研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(6): 33-40.
[44] Anker, S.D., Usman, M.S., Anker, M.S., Butler, J., Böhm, M., Abraham, W.T., et al. (2023) Patient Phenotype Profiling in Heart Failure with Preserved Ejection Fraction to Guide Therapeutic Decision Making. a Scientific Statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension. European Journal of Heart Failure, 25, 936-955. [Google Scholar] [CrossRef] [PubMed]