Right ventricular free-wall longitudinal speckle tracking strain as a prognostic criterion of adverse outcomes in patients with pulmonary hypertension: a systematic review and meta-analysis

The absence of consensus regarding the reference values of right ventricular free wall longitudinal strain (RVFWLS) and its predictive value prompted us to conduct a systematic review and meta-analysis of publications on the predictive role of this parameter in patients with pulmonary hypertension (PH).

Aim. To study the independent predictive value of RVFWLS in PH patients using 2D/3D speckle tracking echocardiography.

Material and methods. Firstly, 317 publications (PubMed) and 857 Google Scholar results were selected. Of the initially identified search results, 12 articles were analyzed. The papers were cohort designed.

Results. The total number of patients with PH was 1281. The mean age of patients was 54,7±6,8 years. Four studies compared the RVFWLS with a control group (n=251). The mean RVFWLS were -17,0±2,4% and -24,7±2,2% in the experimental and control groups, respectively. A meta-analysis of the difference between the mean RVFWLS values in experimental and control group patients showed its total increase in PH subjects of 8,06% (95% CI: 5,18-10,94%; p<0,00001).

The total number of deaths was 268 (all-cause — 180, composite endpoint — 88). According to the meta-analysis, with an increase of 1% in RVFWLS, there is an increase in mean all-cause mortality risk by 14% (p<0,00001), as well as mean risk of adverse outcomes or PH-related events (composite endpoint) by 14% (p<0,0001).

Conclusion. These results highlight the high independent predictive value of RVFWLS as a predictor of adverse outcomes or events associated with a right ventricular dysfunction progression in PH patients.

1. Vonk-Noordegraaf A, Haddad F, Chin KM, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62(25 Suppl):D22-33. doi:10.1016/j.jacc.2013.10.027.

2. Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010;122(2):164-72. doi:10.1161/CIRCULATIONAHA.109.898122.

3. Forfia PR, Fisher MR, Mathai SC, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174(9):1034-41. doi:10.1164/rccm.200604-547OC.

4. Bossone E, Bodini BD, Mazza A, et al. Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005;127(5):1836-43. doi:10.1378/chest.127.5.1836.

5. Fine NM, Chen L, Bastiansen PM, et al. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging. 2013;6(5):711-21. doi:10.1161/CIRCIMAGING.113.000640.

6. Goda A, Ryo K, Delgado-Montero A, et al. The Prognostic Utility of a Simplified Biventricular Echocardiographic Index of Cardiac Remodeling in Patients with Pulmonary Hypertension. J Am Soc Echocardiogr. 2016;29(6):554-60. doi:10.1016/j.echo.2016.02.013.

7. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:903-75. doi:10.1183/13993003.01032-2015.

8. Alekhin MN. Ultrasound techniques for assessing myocardial deformation and their clinical significance. Two-dimensional tracking of gray-scale spots of an ultrasound image of the myocardium in the assessment of its deformation and twisting (Lecture 2). Ultrasound and functional diagnostics. 2011;3:107-20. (In Russ.)

9. Li Y, Xie M, Wang X, et al. Impaired Right and Left Ventricular Function in Asymptomatic Children with Repaired Tetralogy of Fallot by Two-Dimensional Speckle Tracking Echocardiography Study. Echocardiography. 2015;32(1):135-43. doi:10.1111/echo.12581.

10. Xie M, Li Y, Cheng TO, et al. The effect of right ventricular myocardial remodeling on ventricular function as assessed by two-dimensional speckle tracking echocardiography in patients with tetralogy of Fallot: A single center experience from China. International Journal of Cardiology. 2015;178:300-7. doi:10.1016/j.ijcard.2014.10.027.

11. Golukhova EZ, Slivneva IV, Rybka MM, et al. Pulmonary hypertension as a risk assessment factor for unfavorable outcome in patients with COVID-19. Russian Journal of Cardiology. 2020;25(12):4136. (In Russ.) doi:10.15829/1560-4071-2020-4136.

12. Golukhova EZ, Slivneva IV, Rybka MM, et al. Right ventricular systolic dysfunction as a predictor of adverse outcome in patients with COVID-19. Kardiologiia. 2020;60(11):16-29. (In Russ.) doi:10.18087/cardio.2020.11.n1303.

13. da Costa Junior AA, Ota-Arakaki JS, Ramos RP, et al. Diagnostic and prognostic value of right ventricular strain in patients with pulmonary arterial hypertension and relatively preserved functional capacity studied with echocardiography and magnetic resonance. Int J Cardiovasc Imaging. 2017;33(1):39-46. doi:10.1007/s10554-016-0966-1.

14. Wright L, Dwyer N, Wahi S, et al. Relative Importance of Baseline and Longitudinal Evaluation in the Follow-Up of Vasodilator Therapy in Pulmonary Arterial Hypertension. JACC Cardiovasc Imaging. 2019;12(11 Pt 1):2103-11. doi:10.1016/j.jcmg.2018.08.017. Erratum in: JACC Cardiovasc Imaging. 2020;13(9):2068. doi:10.1016/j.jcmg.2019.11.003.

15. Prihadi EA, van der Bijl P, Dietz M, et al. Prognostic Implications of Right Ventricular Free Wall Longitudinal Strain in Patients With Significant Functional Tricuspid Regurgitation. Circulation: Cardiovascular Imaging. 2019;12(3):e008666. doi:10.1161/CIRCIMAGING.118.008666.

16. Moher D, Liberati A, Tetzlaff J, et al. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.

17. Hardegree EL, Sachdev A, Villarraga HR, et al. Role of serial quantitative assessment of right ventricular function by strain in pulmonary arterial hypertension. Am J Cardiol. 2013;111(1):143-8. doi:10.1016/j.amjcard.2012.08.061.

18. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713; quiz 786-8. doi:10.1016/j.echo.2010.05.010.

19. 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. Eur Heart J Cardiovasc Imaging. 2015;16(3):233-70. doi:10.1093/ehjci/jev014. Erratum in: Eur Heart J Cardiovasc Imaging. 2016;17(4):412. doi:10.1093/ehjci/jew041. Erratum in: Eur Heart J Cardiovasc Imaging. 2016;17(9):969. doi:10.1093/ehjci/jew124.

20. Li Y, Wang T, Haines P, et al. Prognostic Value of Right Ventricular Two-Dimensional and Three-Dimensional Speckle-Tracking Strain in Pulmonary Arterial Hypertension: Superiority of Longitudinal Strain over Circumferential and Radial Strain. J Am Soc Echocardiogr. 2020;33(8):985-94.e1. doi:10.1016/j.echo.2020.03.015.

21. Voigt J-U, Pedrizzetti G, Lysyansky P, et al. Definition for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging. 2015;16(1):1-11. doi:10.1093/ehjci/jeu184.

22. Lafitte S, Pillois X, Reant P, et al. Estimation of pulmonary pressures and diagnosis of pulmonary hypertension by Doppler echocardiography: a retrospective comparison of routine echocardiography and invasive hemodynamics. J Am Soc Echocardiogr. 2013;26(5):457-63. doi:10.1016/j.echo.2013.02.002.

23. Moons KG, Hooft L, Williams K, et al. Implementing systematic reviews of prognosis studies in Cochrane. Cochrane Database Syst Rev. 2018;10:ED000129. doi:10.1002/14651858.ED000129.

24. Hayden JA, van der Windt DA, Cartwright JL, et al. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280-6. doi:10.7326/0003-4819-158-4-201302190-00009.

25. Henein MY, Gronlund C, Tossavainen E, et al. Right and left heart dysfunction predict mortality in pulmonary hypertension. Clin Physiol Funct Imaging. 2017;37(1):45-51. doi:10.1111/cpf.12266.

26. Simonneau G, Galie N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):5S-12S. doi:10.1016/j.jacc.2004.02.037.

27. Sachdev A, Villarraga HR, Frantz RP, et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest. 2011;139(6):1299-309. doi:10.1378/chest.10-2015.

28. Haeck ML, Scherptong RW, Marsan NA, et al. Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging. 2012;5(5):628-36. doi:10.1161/CIRCIMAGING.111.971465.

29. Giusca S, Jurcut R, Coman IM, et al. Right ventricular function predicts clinical response to specific vasodilator therapy in patients with pulmonary hypertension. Echocardiography. 2013;30(1):17-26. doi:10.1111/j.1540-8175.2012.01809.x.

30. Sano H, Tanaka H, Motoji Y, et al. Right ventricular function and right-heart echocardiographic response to therapy predict long-term outcome in patients with pulmonary hypertension. Can J Cardiol. 2015;31(4):529-36. doi:10.1016/j.cjca.2015.01.027.

31. van Kessel M, Seaton D, Chan J, et al. Prognostic value of right ventricular free wall strain in pulmonary hypertension patients with pseudo-normalized tricuspid annular plane systolic excursion values. Int J Cardiovasc Imaging. 2016;32(6):905-12. doi:10.1007/ s10554-016-0862-8. Erratum in: Int J Cardiovasc Imaging. 2017;33(4):585. doi:10.1007/s10554-016-1025-7.

32. Murata M, Tsugu T, Kawakami T, et al. Right ventricular dyssynchrony predicts clinical outcomes in patients with pulmonary hypertension. Int J Cardiol. 2017;228:912-8. doi:10.1016/j.ijcard.2016.11.244.

33. Unlu S, Farsalinos K, Ameloot K, et al. Apical traction: a novel visual echocardiographic parameter to predict survival in patients with pulmonary hypertension. Eur Heart J Cardiovasc Imaging. 2016;17(2):177-83. doi:10.1093/ehjci/jev131.

34. Vonk Noordegraaf A, Chin KM, Haddad F, et al. Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update. Eur Respir J. 2019;53(1):1801900. doi:10.1183/13993003.01900-2018.

35. Sanz J, Sanchez-Quintana D, Bossone E, et al. Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(12):1463-82. doi:10.1016/j.jacc.2018.12.076.

36. Tello K, Dalmer A, Axmann J, et al. Reserve of Right Ventricular-Arterial Coupling in the Setting of Chronic Overload. Circ Heart Fail. 2019;12(1):e005512. doi:10.1161/CIRCHEARTFAILURE.118.005512.

37. Chin KM, Kim NH, Rubin LJ. The right ventricle in pulmonary hypertension. Coron Artery Dis. 2005;16(1):13-8. doi:10.1097/00019501-200502000-00003.

38. Zhai YN, Li AL, Tao XC, et al. Regional right ventricular longitudinal systolic strain for detection of severely impaired right ventricular performance in pulmonary hypertension. Echocardiography. 2020;37(4):592-600. doi:10.1111/echo.14639.

39. Leather HA, Ama' R, Missant C, et al. Longitudinal but not circumferential deformation reflects global contractile function in the right ventricle with open pericardium. Am J Physiol Heart Circ Physiol. 2006;290(6):H2369-75. doi:10.1152/ajpheart.01211.2004.

40. Ozawa K, Funabashi N, Tanabe N, et al. Contribution of myocardial layers of right ventricular free wall to right ventricular function in pulmonary hypertension: Analysis using multilayer longitudinal strain by two-dimensional speckle-tracking echocardiography. Int J Cardiol. 2016;215:457-62. doi:10.1016/j.ijcard.2016.04.019.

41. Torrent-Guasp F, Ballester M, Buckberg GD, et al. Spatial orientation of the ventricular muscle band: physiologic contribution and surgical implications. J Thorac Cardiovasc Surg. 2001;122(2):389-92. doi:10.1067/mtc.2001.113745.

42. Shukla M, Park JH, Thomas JD, et al. Prognostic Value of Right Ventricular Strain Using Speckle-Tracking Echocardiography in Pulmonary Hypertension: A Systematic Review and Meta-analysis. Can J Cardiol. 2018;34(8):1069-78. doi:10.1016/j.cjca.2018.04.016.

43. Levy PT, Sanchez Mejia AA, Machefsky A, et al. Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2014;27(5):549-60,e3. doi:10.1016/j.echo.2014.01.015.

44. Fine NM, Chen L, Bastiansen PM, et al. Reference Values for Right Ventricular Strain in Patients without Cardiopulmonary Disease: A Prospective Evaluation and Meta-Analysis. Echocardiography. 2015;32(5):787-96. doi:10.1111/echo.12806.

45. Park JH, Choi JO, Park SW, et al. Normal references of right ventricular strain values by two-dimensional strain echocardiography according to the age and gender. Int J Cardiovasc Imaging. 2018;34(2):177-83. doi:10.1007/s10554-017-1217-9.

46. Muraru D, Onciul S, Peluso D, et al. Sex- and Method-Specific Reference Values for Right Ventricular Strain by 2-Dimensional Speckle-Tracking Echocardiography. Circ Cardiovasc Imaging. 2016;9(2):e003866. doi:10.1161/CIRCIMAGING.115.003866.

47. Meris A, Faletra F, Conca C, et al. Timing and magnitude of regional right ventricular function: a speckle tracking-derived strain study of normal subjects and patients with right ventricular dysfunction. J Am Soc Echocardiogr. 2010;23(8):823-31. doi:10.1016/j.echo.2010.05.009.

48. Chia EM, Hsieh CH, Boyd A, et al. Effects of age and gender on right ventricular systolic and diastolic function using two-dimensional speckle-tracking strain. J Am Soc Echocardiogr. 2014;27(10):1079-86.e1. doi:10.1016/j.echo.2014.06.007.

49. Motoji Y, Tanaka H, Fukuda Y, et al. Efficacy of right ventricular free-wall longitudinal speckle-tracking strain for predicting long-term outcome in patients with pulmonary hypertension. Circ J. 2013;77(3):756-63. doi:10.1253/circj.cj-12-1083. Epub 2012 Dec 7. PMID: 23220860.

50. Miotti C, Papa S, Manzi G, et al. The Growing Role of Echocardiography in Pulmonary Arterial Hypertension Risk Stratification: The Missing Piece. J Clin Med. 2021;10(4):619. doi:10.3390/jcm10040619.

51. Mazurek JA, Vaidya A, Mathai SC, et al. Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension. Pulm Circ. 2017;7(2):361-71. doi:10.1177/2045893217694175.

52. Park JH, Park MM, Farha S, et al. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension. J Cardiovasc Ultrasound. 2015;23(2):91-9. doi:10.4250/jcu.2015.23.2.91.

53. Yoshifuku S, Otsuji Y, Takasaki K, et al. Pseudonormalized Doppler total ejection isovolume (Tei) index in patients with right ventricular acute myocardial infarction. Am J Cardiol. 2003;91(5):527-31. doi:10.1016/s0002-9149(02)03299-x.

54. Moceri P, Baudouy D, Chiche O, et al. Imaging in pulmonary hypertension: Focus on the role of echocardiography. Arch Cardiovasc Dis. 2014;107(4):261-71. doi:10.1016/j. acvd.2014.02.005.

55. Mertens LL, Friedberg MK. Imaging the right ventricle-current state of the art. Nat Rev Cardiol. 2010;7(10):551-63. doi:10.1038/nrcardio.2010.118.

56. Moceri P, Duchateau N, Baudouy D, et al. Three-dimensional right-ventricular regional deformation and survival in pulmonary hypertension. Eur Heart J Cardiovasc Imaging. 2018;19(4):450-8. doi:10.1093/ehjci/jex163.

57. Hulshof HG, Eijsvogels TMH, Kleinnibbelink G, et al. Prognostic value of right ventricular longitudinal strain in patients with pulmonary hypertension: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging. 2019;20(4):475-84. doi:10.1093/ehjci/jey120.

58. Fukuda Y, Tanaka H, Sugiyama D, et al. Utility of right ventricular free wall speckletracking strain for evaluation of right ventricular performance in patients with pulmonary hypertension. J Am Soc Echocardiogr. 2011;24(10):1101-8. doi:10.1016/j.echo.2011.06.005.

59. Pirat B, McCulloch ML, Zoghbi WA. Evaluation of global and regional right ventricular systolic function in patients with pulmonary hypertension using a novel speckle tracking method. Am J Cardiol. 2006;98(5):699-704. doi:10.1016/j.amjcard.2006.03.056.

60. Teske AJ, Prakken NH, De Boeck BW, et al. Echocardiographic tissue deformation imaging of right ventricular systolic function in endurance athletes. Eur Heart J. 2009;30(8):969-77. doi:10.1093/eurheartj/ehp040.