Variants and role of hypotension in heart failure: rationale and design of an additional study of ORTHO-HYPO within the CARMEN-CHF program

As part of the observational, multicenter prospective study CardioReno-Hepato-Metabolic Disease in Chronic Heart Failure (CARMENCHF), an additional exploratory study of the types and role of hypotension in heart failure (ORTHO-HYPO) was specifically designed to thoroughly examine hypotension. The study aim is to assess the frequency and types of orthostatic hypotension and orthostatic hypertension and their associations with clinical and demographic characteristics, comorbidity, severity of clinical manifestations of heart failure, and outcomes. In this sub-study, in addition to the routine examination, an active "supine-standing" orthostatic test and 24-h blood pressure and ECG monitoring will be performed.

1. Drapkina OM, Boytsov SA, Omelyanovskiy VV, et al. Socioeconomic impact of heart failure in Russia. Russian Journal of Cardiology. 2021;26(6):4490. (In Russ.) doi:10.15829/1560-4071-2021-4490.

2. Polyakov DS, Fomin IV, Belenkov YuN, et al. Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study. Kardiologiia. 2021;61(4):4-14. (In Russ.) doi:10.18087/cardio.2021.4.n1628.

3. Soloveva AE, Medvedev AE, Lubkovsky AV, et al. Total, ageand sex-specific mortality after discharge of patients with heart failure: the first large-scale cohort real-world study on Russian population. Russian Journal of Cardiology. 2024;29(6):5940. (In Russ.) doi:10.15829/1560-4071-2024-5940. EDN: CTTQTF.

4. Vaduganathan M, Claggett BL, Chatur S, et al. Lifetime Benefits of Comprehensive Medical Therapy in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. Nat Med. 2026;32:325-31. doi:10.1038/s41591-025-04037-3.

5. Vaduganathan M, Claggett BL, Jhund PS, et al. Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Lancet. 2020;396(10244):121-8. doi:10.1016/S01406736(20)30748-0.

6. Shlyakhto EV, Belenkov YuN, Boytsov SA, et al. Use of guidelinedirected medical therapy in outpatients with heart failure in realworld practice: a subanalysis of PRIORITY-HF study. Russian Journal of Cardiology. 2025;30(11S):6517. (In Russ.) doi:10.15829/1560-4071-2025-6517. EDN: WFHVQR.

7. Savarese G, Lindberg F, Christodorescu RM, et al. Physician perceptions, attitudes, and strategies towards implementing guideline-directed medical therapy in heart failure with reduced ejection fraction. A survey of the Heart Failure Association of the ESC and the ESC Council for Cardiology Practice. Eur J Heart Fail. 2024;26(6):1408-18. doi:10.1002/ejhf.3214.

8. Shlyakhto EV, Belenkov YuN, Boytsov SA, et al. Characteristics and outcomes in outpatients with heart failure in Russia: results of a large-scale prospective observational multicenter registry study PRIORITY-HF. Russian Journal of Cardiology. 2025;30(11S):6516. (In Russ.). doi:10.15829/1560-4071-2025-6516. EDN: DZOXMG.

9. Musella F, Rosano GMC, Hage C, et al. Patient profiles in heart failure with reduced ejection fraction: Prevalence, characteristics, treatments and outcomes in a real-world heart failure population. Eur J Heart Fail. 2023;25(8):1246-53. doi:10.1002/ejhf.2892.

10. Mareev VYu, Kapanadze LG, Kheimets GI, et al. Effect of 24-hour blood pressure and heart rate on the prognosis of patients with reduced and midrange LVEF. Kardiologiia. 2021;61(7):4-13. (In Russ.) doi:10.18087/cardio.2021.7.n1684.

11. Soloveva A, Fedorova D, Villevalde S, et al. Addressing Orthostatic Hypotension in Heart Failure: Pathophysiology, Clinical Implications and Perspectives. J Cardiovasc Transl Res. 2020; 13(4):549-69. doi:10.1007/s12265-020-10044-1.

12. Skvortsov A, Mareev V, Nasonova S, et al. Triple combination may provoke hypotension which is associated with RAAS and SAS reactivation in CHF patients. European Journal of Heart Failure. 2007;6(1):123.

13. Soloveva A, Fedorova D, Kuchinskaia S, et al. Profiling hypotension in heart failure based on office, orthostatic and ambulatory blood pressure measurements. European Journal of Heart Failure. 2025;27(9):1695-6. doi:10.1002/ejhf.3715.

14. Soloveva A, Fedorova D, Fudim M, et al. Blood Pressure Response and Symptoms During Active Standing Test Among Hospitalized and Outpatients With Heart Failure: Results From the GRAVITY-HF Prospective Observational Cohort Study. J Card Fail. 2024;30(7):890-903. doi:10.1016/j.cardfail.2023.12.017.

15. Newton JL, Pairman J, Wilton K, et al. Fatigue and autonomic dysfunction in non-alcoholic fatty liver disease. Clin Auton Res. 2009;19(6):319-26. doi:10.1007/s10286-009-0031-4.

16. Fudim M, Sobotka PA, Dunlap ME. Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease. Circ Heart Fail. 2021;14(1): e007308. doi:10.1161/CIRCHEARTFAILURE.120.007308.

17. Mareev VYu, Soloveva AE, Begrambekova YuL, et al. Cardiac-renal-hepatic-metabolic disease in chronic heart failure (CARMENCHF): rationale and design of an observational multicenter prospective study. Cardiovascular Therapy and Prevention. 2026; 25(3):4725. (In Russ.) doi:10.15829/1728-8800-2026-4725.

18. Sharman JE, LaGerche A. Exercise blood pressure: clinical relevance and correct measurement. J Hum Hypertens. 2015;29(6): 351-8. doi:10.1038/jhh.2014.84.

19. Jordan J, Biaggioni I, Kotsis V, et al. Consensus statement on the definition of orthostatic hypertension endorsed by the American Autonomic Society and the Japanese Society of Hypertension. Clin Auton Res. 2023;33(1):69-73. doi:10.1007/s10286-02200897-8.

20. Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72. doi:10.1007/s10286-011-0119-5.

21. Magder S. The meaning of blood pressure. Crit Care. 2018; 22(1):257. doi:10.1186/s13054-018-2171-1.

22. Böhm M, Anker SD, Butler J, et al. Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure. J Am Coll Cardiol. 2021;78(13):1337-48. doi:10.1016/j.jacc.2021.07.049.

23. Girerd N, Coiro S, Benson L, et al. Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry. Eur J Heart Fail. 2024;26:359-69. doi:10.1002/ejhf.3066.