Heart failure with preserved ejection fraction in middle-aged women and history of adverse pregnancy outcomes

Aim. To determine the associations between adverse pregnancy outcomes (APOs) and the presence of heart failure with preserved ejection fraction (HFpEF) in middleaged women.

Material and methods. The study included 102 women aged 45-59 years with a history of at least one completed pregnancy. The examination protocol involved transthoracic echocardiography, with a diastolic stress test when indicated, measurement of NT-proBNP levels, and structured interviews to obtain a history of APOs. Intergroup differences in cardiac structure and function were analyzed, along with associations between APOs and different HFpEF stages.

Results. More advanced HFpEF stages in middle-aged women are associated with more pronounced alterations in cardiac morphofunctional parameters and a higher prevalence of hypertension and proteinuria in their pregnancy history. The heart failure risk factor stage (Stage A) showed no statistically significant associations with APOs (p>0.05). Pre-heart failure (Stage B) was associated with hypertension (odds ratio, OR 3.57 (1.43-8.88), p=0.006), proteinuria (OR 4.92 (1.29-18.84), p=0.02), and preterm birth (OR 3.65 (1.20-11.11), p=0.022). Stage 1 HFpEF (Stage C) was linked to hypertension (OR 3.81 (1.08-13.39), p=0.037) and smoking (OR 4.46 (1.09-18.2), p=0.038) during pregnancy. Women with a history of hypertension during pregnancy exhibited higher blood pressure, greater prevalence of hypertension, diabetes mellitus, signs/symptoms of heart failure, worse echocardiographic parameters, and a higher rate of diastolic dysfunction (37.9% vs. 14.9%, p=0.03) in middle age compared to those without hypertensive disorders of pregnancy.

Conclusion. A history of hypertension, proteinuria, and smoking during pregnancy is associated with various HFpEF stages in the long term. Middle-aged women with a history of gestational hypertension are characterized by more pronounced alterations in cardiac morphofunctional parameters.

1. Borlaug BA, Sharma K, Shah SJ, et al. Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement. J Am Coll Card. 2023;81(18):1810-1834. DOI:10.1016/j.jacc.2023.01.049.

2. Savarese G, Becher PM, Lund LH, et al. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovascular Research. 2022;118(17):3272-3287. DOI:10.1093/cvr/cvac013.

3. Heidenreich PA, Bozkurt B, Aguilar D, et al. 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. 2022;145(18):e895-e1032. DOI:10.1161/CIR.0000000000001063.

4. Omote K, Verbrugge FH, Borlaug BA. Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies. Annu Rev Med. 2022;73:321-337. DOI:10.1146/annurev-med-042220-022745.

5. Nair N. Epidemiology and pathogenesis of heart failure with preserved ejection fraction. Rev Cardiovasc Med. 2020;21(4):531-540. DOI:10.31083/j.rcm.2020.04.154.

6. Ding N, Shah AM, Blaha MJ, et al. Cigarette Smoking, Cessation, and Risk of Heart Failure With Preserved and Reduced Ejection Fraction. J Am Coll Cardiol. 2022;79(23):2298-2305. DOI:10.1016/j.jacc.2022.03.377.

7. Beale AL, Meyer P, Marwick TH, et al. Sex Differences in Cardiovascular Pathophysiology: Why Women Are Overrepresented in Heart Failure With Preserved Ejection Fraction. Circulation. 2018;138(2):198-205. DOI:10.1161/CIRCULATIONAHA.118.034271.

8. Hansen AL, Søndergaard MM, Hlatky MA, et al. Adverse Pregnancy Outcomes and Incident Heart Failure in the Women’s Health Initiative. JAMA Netw Open. 2021;4(12):e2138071. DOI:10.1001/jamanetworkopen.2021.38071.

9. Briller JE, Mogos MF, Muchira JM, et al. Pregnancy Associated Heart Failure With Preserved Ejection Fraction: Risk Factors and Maternal Morbidity. J Card Fail. 2021;27(2):143-152. DOI:10.1016/j.cardfail.2020.12.020.

10. Garovic VD, White WM, Vaughan L, et al. Incidence and Long-Term Outcomes of Hypertensive Disorders of Pregnancy. Journal of the American College of Cardiology. 2020;75(18):2323-2334. DOI:10.1016/j.jacc.2020.03.028.

11. 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 Heart Fail. 2020;8(3):172-184. DOI:10.1016/j.jchf.2019.09.009.

12. Matskeplishvili ST, Saidova MA, Mironenko MU, et al. Performing standard transthoracic echocardiography. Methodological recommendations 2024. Russ J Cardiol. 2025;30(2):6271. DOI:10.15829/1560-4071-2025-6271 (in Russ.)

13. Smiseth OA, Morris DA, Cardim N, et al. Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging. European Heart Journal - Cardiovascular Imaging. 2022;23(2):e34-e61. DOI:10.1093/ehjci/jeab154.

14. Lang RM, Badano LP, Mor-Avi V, et al. 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. 2015;28(1):1-39.e14. DOI:10.1016/j.echo.2014.10.003.

15. Galyavich AS, Tereshchenko SN, Uskach TM, et al. 2024 Clinical practice guidelines for Chronic heart failure. Russ J Cardiol. 2024;29(11):6162 (in Russ.)

16. 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. DOI:10.1093/eurheartj/ehz641.

17. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726. DOI:10.1093/eurheartj/ehab368.

18. 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. DOI:10.1002/ejhf.1614.

19. Verbrugge FH, Omote K, Reddy YNV, et al. Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality. Eur Heart J. 2022;43(20):1941-1951. DOI:10.1093/eurheartj/ehab911.

20. Ying W, Catov JM, Ouyang P. Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk. Journal of the American Heart Association. 2018;7(17):e009382. DOI:10.1161/JAHA.118.009382.

21. Chulkov VS, Syundyukova EG, Chulkov VS, et al. Hypertensive disorders during pregnancy and the risk of cardiovascular diseases. Preventive Medicine. 2021;24(12):97-104. DOI:10.17116/profmed20212412197 (in Russ.)

22. Umar S, Banerjee S, Datta S, et al. Perinatal Nicotine Exposure in Rats Leads to HFpEF, Pulmonary Hypertension, and Right Ventricular Hypertrophy Which Are Attenuated by a Potent PPARγ Agonist Rosiglitzaone. Am J Respir Crit Care Med 2024;209:A6807. DOI:10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A6807.