Cover Image

Study of left ventricle ejection fraction and natriuretic peptides in patients with heart failure treated with systemic medical ozone.


Heart Failure (HF) is a prevalent disease and is a frequent reason for consultation. It is a complex entity that presents multiple pathophysiological aspects, and it is sometimes difficult to establish an adequate diagnosis, since its signs and symptoms may overlap with those of other diseases. For a better diagnosis and control of this pathology, it is currently essential to follow up through echocardiography and the determination of natriuretic peptides, since this increase significantly in patients with heart failure, having a negative predictive value for these patients. For this reason, we set out to study the effects of rectal ozone treatment on cardiac contractility and natriuretic peptides in patients with heart failure.
We conducted a study with two groups of 6 patients each, who had a diagnosis of Class II-III Chronic HF according to the functional classification of the New York Heart Association (NYHA) and the American Cardiology College / American Heart Association (ACC/AHA), Echocardiogram with a Left Ventricular Ejection Fraction (LVEF) less than 50% and dosage of Elevated Natriuretic Peptides. We administer ozone rectally through insufflation, with a 20-session protocol (increasing concentration and volume every 5 sessions until reaching 300 ml), performing the following treatment scheme: 5 sessions with 25 ?g/ml concentration and 200 ml volume, 5 sessions with 30 ?g/ml and 250 ml, 5 sessions with 35 ?g/ml and 300 ml and the last 5 sessions with 40 ?g/ml and 300 ml volume.
As a result, it was obtained that ozone treatment through rectal insufflation, through its anti-inflammatory and immunomodulatory effects, was able to improve the clinical status of the study group, significantly reducing below 50% the values of the natriuretic peptide that was elevated at the beginning and the ejection fraction of the left ventricle was significantly increased. Concluding in this way that ozone administration by rectal route as a complement to conventional treatment significantly increased the ejection fraction of the left ventricle, and decreased the values of natriuretic peptide, significantly improving the quality of life of these patients.


heart failure; left ventricular ejection fraction; natriuretic peptide; rectal insufflation; ozone therapy

Full Text:



  1. Salomone OA. Los péptidos natriuréticos en la insuficiencia cardiaca: mejorando el diagnostico y manejo del síndrome [Natriuretic peptides in heart failure: improving the diagnosis and management of the syndrome]. Rev Esp Cardiol. 2002,55(1):4-6.

  2. Puschendorf B, Mair J. Cardiac natriuretic peptides: new laboratory parameters in heart failure patients. Clin Lab. 2001;47:265-67.

  3. Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J. 1998 May;135(5):825-32.

  4. Pfister R, Schneider CA. Natriuretic peptides BNP and NT-pro- BNP: established laboratory markers in clinical practice or just perspectives? Clin Chim Acta. 2004;349: 25-38.

  5. Cowie MR, Struthers AD, Wood DA, Coats AS, Thompson SG, PooleWilson PA et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet. 1997 Nov 8;350(9088):1349-53.

  6. Hobbs FD, Davis RC, Roalfe AK, Hare R, Davies MK, Kenkre JE. Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations. BMJ. 2002 Jun 22;324(7352):1498.

  7. Hogenhuis J, Voors AA, Jaarsma T, Hoes AW, Hillege HL, Kragten JA, van Veldhuisen DJ. Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure. Eur J Heart Fail. 2007 Aug;9(8):787-94.

  8. Ewald B, Ewald D, Thakkinstian A, Attia J. Meta-analysis of B type natriuretic peptide and N-terminal pro B natriuretic peptide in the diagnosis of clinical heart failure and population screening for left ventricular systolic dysfunction. Intern Med J. 2008;38:101-13.

  9. Bocci V, Valacchi G, Corradeschi F, Aldinucci C, Silvestri S, Paccagnini E, Gerli R. Studies on the biological effects of ozone: 7. Generation of reactive oxygen species (ROS) after exposure of human blood to ozone. J Biol Regul Homeost Agents. 1998;12(3):67-75.

  10. Bocci V, Borreli E, Travagli V, Zanardi I. The ozone paradox: Ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009;29 (4): 646-82.

  11. Re L, Mawsouf MN, Menendez S, Leon OS, Sanchez GM y Hernandez F. Ozone Therapy: Clinical and Basic Evidences of its Therapeutic Potential. Arch Med Res. 2008;39:17-26.

  12. Schwartz A, Martínez G, Gonzalez E, Clavo B, Hernández M. Manual de ozonoterapia clinica [Clinical ozone therapy manual]. Madrid: Medizeus- Soluciones medicas S.L.; c2017. Chapter 5, Ozonoterapia en las enfermedades cardiovasculares [Ozone therapy in cardiovascular diseases]; p. 145-169.

  13. Baeza-Noci J, Cabo-Soler JR, Moraleda-Gomez M, Menendez-Cepedo S, Re L. WFOT’s Review on Evidence Based Ozone Therapy [Internet]. Brescia: WFOT; 2015[cited 2021 Mar 19]. Available from:

  14. Cespedes-Suarez J, Martin-Serrano Y, Carballosa-Peña MR, Dager-Carballosa DR. Clinical study of patients with failure under treatment with ozone therapy. J Ozone Ther. 2019:2(3).

  15. Ewald B, Ewald D, Thakkinstian A, Attia J. Meta-analysis of B type natriuretic peptide and N-terminal pro B natriuretic peptide in the diagnosis of clinical heart failure and population screening for left ventricular systolic dysfunction. Intern Med J. 2008;38:101-13.

  16. Borroto-Rodriguez V, Suarez-Fleitas LR, Bocci V, Luisa B. Lima-Hernandez LB, Cambara-Peña R, Lima-Gonzalez S. Ozonoterapia en la Insuficiencia Cardiaca Crónica [Ozone therapy in chronic heart failure]. Rev Esp Ozonoter. 2016;6(1):9-26.

  17. Menendez S, Leon OS, Calunga JL, Copello M, Weiser M. Advances of Ozone Therapy in Medicine and Dentistry. Santa Barbara (CA): Ozone Therapies Group; 2016.

  18. Xing B, Chen H, Wang L, Weng X, Chen Z and Li X. Ozone oxidative preconditioning protects the rat kidney from reperfusion injury via modulation of the TLR4-NF-κB pathway. Acta Cir Bras. 2015 Jan;30(1):60-66.

  19. Galie M, Covi V, Tabaracci G, Malatesta M. The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure. Int. J. Mol. Sci. 2019 Aug;20(16):4009.

  20. Hidalgo-Tallon FJ, Menendez-Cepero Silvia, Baeza-Noci Jose, Gea-Carrasco G. Theoretical Basements for a Clinical Trial on COVID-19 Patients with Systemic Ozone Therapy. J Neurol Neurocrit Care. 2021;4(1):1–6.

  21. Vaillant JD, Fraga A, Díaz MT, Mallok A, Viebahn-Hänsler R, Fahmy Z, Barbera A, Delgado L, Menendez S, Fernandez OS. Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats. Eur J Pharmacol. 2013;714 (1-3):318-24.

  22. Ponikowsk P et al. Patogenia y presentación clínica de la insuficiencia cardiaca aguda [Pathogenesis and clinical presentation of acute heart failure]. Rev Esp Cardiol. 2015;68(4):300-10.

  23. Wang Z, Zhang A, Meng W, Wang T, Li D, Liu Z, Liu H. Ozone protects the rat lung from ischemia-reperfusion injury by attenuating NLRP3-mediated inflammation, enhancing Nrf2 antioxidant activity and inhibiting apoptosis. Eur J Pharmacol. 2018 Sep 15;835:82-93.

  24. Izadi M, Tahmasebi S, Pustokhina I, Yumashev AV, Lakzaei T, Alvanegh AG, Ahmadi M. Changes in Th17 cells frequency and function after ozone therapy used to treat multiple sclerosis patients. Mult Scler Relat Disord. 2020 Nov;46:102466.


  • There are currently no refbacks.

WFOTJournal of Ozone Therapy (JO3T)
The Official Peer Reviewed Journal of the World Federation of Ozone Therapy (WFOT)
ISSN 2444-9865