Influence of intravenous ferric carboxymaltose on non-invasive parameters of left ventricular myocardial work in patients with heart failure with reduced ejection fraction

Aim. To assess non-invasive parameters of left ventricular (LV) myocardial work in patients with heart failure with reduced ejection fraction (CHrEF) and iron deficiency (ID) after ferric carboxymaltose (FCM) therapy.

Material and methods. There were following inclusion criteria: LV ejection fraction (EF) ≤40%; body >70 kg, receiving best medical therapy (BMT) in recommended doses in accordance with the guidelines of the European Society of Cardiology and the Russian Society of Cardiology. Median age was 67±11,7 years (men, 83%), while median LVEF and N-terminal pro-brain natriuretic peptide was 29% and 315 ng/ml, respectively. Patients were randomized by the envelope method. The first group consisted of 19 patients who received therapy with intravenous FCM 1500 mg in 2 injections with an interval of one week between injections in addition to BMT. The control group consisted of 16 patients who received BMT without FCM. All patients underwent a standard echocardiography, and non-invasive LV myocardial work was assessed immediately before inclusion in the study and after 3 months.

Results. In the first group of patients receiving FCM therapy, an increase in LVEF (29,1±10,3 vs 35,4±11,1; p=0,001), mitral annular plane systolic excursion (1,2 (1;1,6 ) vs 1,5 (1,3;1,9), p=0,001), LV global longitudinal strain (-7 (-5;-8) vs -8 (-6;-11), p=0,007) and non-invasive indicators of myocardial work (global work index (826±314 vs 1041±354), p=0,0001; global constructive work (1173±388 vs 1435±405), p=0,0001; global work efficiency (85 (82;87) vs 86 (82;88), p=0,017)). There were no significant changes in the studied parameters in the BMT group.

Conclusion. Patients with HFrEF and ID treated with FCM showed a significant increase in LV systolic function, including non-invasive myocardial work parameters, compared with the control group. 

1. Pellikka PA, She L, Holly TA, et al. Variability in Ejection Fraction Measured By Echocardiography, Gated Single-Photon Emission Computed Tomography, and Cardiac Magnetic Resonance in Patients With Coronary Artery Disease and Left Ventricular Dysfunction. JAMA Netw Open. 2018;1(4):e181456. doi:10.1001/jamanetworkopen. 2018.1456.

2. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021;42(35):3427-520. doi:10.1093/eurheartj/ehab364Monge.

3. Spitzer E, Ren B, Zijlstra F, et al. The Role of Automated 3D Echocardiography for Left Ventricular Ejection Fraction Assessment. Card Fail Rev. 2017;3(2):97-101. doi:10.15420/cfr.2017:14.1.

4. Risum N, Ali S, Olsen NT, et al. Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults. J Am Soc Echocardiogr. 2012;25(11):1195-203. doi:10.1016/j.echo.2012.08.007.

5. Yingchoncharoen T, Agarwal S, Popović ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr. 2013;26(2):185-91. doi:10.1016/j.echo.2012.10.008.

6. Russell K, Eriksen M, Aaberge L, et al. A novel clinical method for quantification of reIDonal left ventricular pressure-strain loop area: a non-invasive index of myocardial work. Eur Heart J. 2012;33(6):724-33. doi:10.1093/eurheartj/ehs016.

7. Muraru D, Niero A, Rodriguez-Zanella H, et al. Three-dimensional speckle-tracking echocardiography: benefits and limitations of integrating myocardial mechanics with three-dimensional imaIDng. Cardiovasc Diagn Ther. 2018;8(1):101-17. doi:10.21037/cdt.2017.06.01.

8. Park JJ, Mebazaa A, Hwang IC, et al. Phenotyping Heart Failure According to the LonIDtudinal Ejection Fraction Change: Myocardial Strain, Predictors, and Outcomes. J Am Heart Assoc. 2020;9(12):e015009. doi:10.1161/JAHA.119.015009.

9. La Canna G, Scarfo’ I. New and old echographic parameters in heart failure. Eur Heart J Suppl. 2020;22(Suppl L):L86-L92. doi:10.1093/eurheartj/suaa142.

10. 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):3599-726. doi:10.1093/eurheartj/ehab368.

11. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436-48. doi:10.1056/ NEJMoa0908355.

12. López-Vilella R, Lozano-Edo S, Arenas Martín P, et al. Impact of intravenous ferric carboxymaltose on heart failure with preserved and reduced ejection fraction. ESC Heart Fail. 2022;9(1):133-45. doi:10.1002/ehf2.13753.

13. Russian Society of Cardiology (RSC). 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. (In Russ.). doi:10.15829/1560-4071-2020-4083.

14. Alekhin MN, Ivanov SI, Stepanova AI. Noninvasive assessment of left ventricular myocardial function in healthy individuals with echocardiography. Medical Alphabet. 2020;1(14):45-52. (In Russ.) doi:10.33667/2078-5631-2020-14-45-52.

15. Satriano A, Heydari B, Narous M, et al. Clinical feasibility and validation of 3D principal strain analysis from cine MRI: comparison to 2D strain by MRI and 3D speckle tracking echocardiography. Int J Cardiovasc Imaging. 2017;33(12):1979-92. doi:10.1007/s10554-017-1199-7.

16. Russell K, Eriksen M, Aaberge L, et al. Assessment of wasted myocardial work: a novel method to quantify energy loss due to uncoordinated left ventricular contractions. Am J Physiol Heart Circ Physiol. 2013;305(7):H996-H1003. doi:10.1152/ajpheart.00191.2013.

17. Hedwig F, Nemchyna O, Stein J, et al. Myocardial Work Assessment for the Prediction of Prognosis in Advanced Heart Failure. Front Cardiovasc Med. 2021;8:691611. doi:10.3389/fcvm.2021.691611.

18. Wang CL, Chan YH, Wu VC, et al. Incremental prognostic value of global myocardial work over ejection fraction and global longitudinal strain in patients with heart failure and reduced ejection fraction. Eur Heart J Cardiovasc Imaging. 2021;22(3):348-56. doi:10.1093/ehjci/jeaa162.

19. Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131(2S-2):568S-580S. doi:10.1093/jn/131.2.568S.

20. Hoes MF, Grote Beverborg N, Kijlstra JD, et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur J Heart Fail. 2018;20(5):910-9. doi:10.1002/ejhf.1154.

21. Toblli JE, Angerosa M. Optimizing iron delivery in the management of anemia: patient considerations and the role of ferric carboxymaltose. Drug Des Devel Ther. 2014;8:2475- 91. doi:10.2147/DDDT.S55499.