Right ventricular systolic dysfunction as a predictor of adverse outcome in patients with COVID-19

Aim To analyze survival of patients with COVID-19 based on echocardiographic (EchoCG) criteria for evaluation of the right ventricular (RV) systolic function.
Material and methods Data of patients were retrospectively evaluated at the Center for Medical Care of Patients with Coronavirus Infection. Among 142 primarily evaluated patients with documented COVID-19, 110 patients (men/women, 63/47; mean age, 62.3 ± 15.3 years) met inclusion/exclusion criteria. More than 30 EchoCG parameters were analyzed, and baseline data (comorbidities, oxygen saturation, laboratory data, complications, outcomes, etc.) were evaluated. ROC-analysis was used for evaluating the diagnostic significance of different EchoCG parameters for prediction of a specific outcome and its probability. Dependence of the overall survival of patients on different EchoCG parameters was analyzed with the Cox proportional hazards model. For assessing the predictive value of EchoCG parameters for patient stratification by risk of an adverse outcome, a predictive model was developed using the CHAID method.
Results The in-hospital death rate of patients included into the study was 15.5 %, and the death rate for this period of in-hospital observation was 12 %. Based on the single-factor analysis of EchoCG parameters, a multifactor model was developed using the method of Cox regression. The model included two predictors for an unfavorable outcome, estimated pulmonary artery systolic pressure (EPASP) and maximal indexed right atrial volume (RAi), and a preventive factor, right ventricular global longitudinal strain (LS RV). Base risks for fatal outcome were determined with an account of the follow-up time. According to the obtained values, an increase in EPASP by 1 mm Hg was associated with increases in the risk of fatal outcome by 8.6 % and in the RA(i) volume by 1 ml/5.8 %. LS RV demonstrated an inverse correlation; a 1% increase in LS RV was associated with a 13.4% decrease in the risk for an unfavorable outcome. According to the ROC analysis, the most significant determinants of the outcome were the tricuspid annular plane systolic excursion (TAPSE) (AUC, 0.84 ± 0.06; cut-off, 18 mm) and EPASP (AUC, 0.86 ± 0.05; cut-off, 42 mm Hg). Evaluating the effects of different EchoCG predictors, that characterized the condition of the right heart, provided a classification tree. Six final decisions were determined in the model, two of which were assigned to the category of reduced risk for fatal outcome and four were assigned to the category of increased risk. Sensitivity of the classification tree model was 94.1 % and specificity was 89.2 %. Overall diagnostic significance was 90.0±2.9 %.
Conclusion The presented models for statistical treatment of EchoCG parameters reflect the requirement for a comprehensive analysis of EchoCG parameters based on a combination of standard methods for EchoCG evaluation and current technologies of noninvasive visualization. According to the study results, the new EchoCG marker, LS RV, allows identifying the signs of right ventricular dysfunction (particularly in combination with pulmonary hemodynamic indexes), may enhance the early risk stratification in patients with COVID-19, and help making clinical decisions for patients with different acute cardiorespiratory diseases.

1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507–13. DOI: 10.1016/S0140-6736(20)30211-7

2. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. The Journal of Heart and Lung Transplantation. 2020;39(5):405–7. DOI: 10.1016/j.healun.2020.03.012

3. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020;395(10229):1033–4. DOI: 10.1016/S0140-6736(20)30628-0

4. CDC. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). 2020. [Internet] 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html

5. Potere N, Valeriani E, Candeloro M, Tana M, Porreca E, Abbate A et al. Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis. Critical Care. 2020;24(1):389. DOI: 10.1186/s13054-020-03022-1

6. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiology. 2020;5(7):819–24. DOI: 10.1001/jamacardio.2020.1096

7. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054–62. DOI: 10.1016/S0140-6736(20)30566-3

8. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020;8(4):420–2. DOI: 10.1016/S2213-2600(20)30076-X

9. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F et al. Association of Cardiac Injury Цith Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiology. 2020;5(7):802–10. DOI: 10.1001/jamacardio.2020.0950

10. Singh R, Kashyap R, Hutton A, Sharma M, Surani S. A Review of Cardiac Complications in Coronavirus Disease 2019. Cureus. 2020;12(5): e8034. DOI: 10.7759/cureus.8034

11. Minardi J, Marsh C, Sengupta P. Risk-Stratifying COVID-19 Patients the Right Way. JACC Cardiovascular Imaging. 2020;13(11):2300-2303. doi: 10.1016/j.jcmg.2020.05.012

12. Greyson CR. Pathophysiology of right ventricular failure: Critical Care Medicine. 2008;36(1 Suppl):S57–65. DOI: 10.1097/01.CCM.0000296265.52518.70

13. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right Ventricular Function in Cardiovascular Disease, Part I: Anatomy, Physiology, Aging, and Functional Assessment of the Right Ventricle. Circulation. 2008;117(11):1436–48. DOI: 10.1161/CIRCULATIONAHA.107.653576

14. Li Y., Li H., Zhu S, Xie Y, Wang B, He L et al. Prognostic Value of Right Ventricular Longitudinal Strain in Patients with COVID-19. JACC Cardiovasc Imaging. 2020;13(11):2287-2299. DOI: 10.1016/j.jcmg.2020.04.014

15. Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G et al. Current and Evolving Echocardiographic Techniques for the Quantitative Evaluation of Cardiac Mechanics: ASE/EAE Consensus Statement on Methodology and Indications Endorsed

16. by the Japanese Society of Echocardiography. European Journal of Echocardiography. 2011;12(3):167–205. DOI: 10.1093/ejechocard/jer021

17. Longobardo L, Suma V, Jain R, Carerj S, Zito C, Zwicke DL et al. Role of Two-Dimensional Speckle-Tracking Echocardiography Strain in the Assessment of Right Ventricular Systolic Function and Comparison with Conventional Parameters. Journal of the American Society of Echocardiography. 2017;30(10):937-946.e6. DOI: 10.1016/j.echo.2017.06.016

18. Li Y, Xie M, Wang X, Lu Q, Zhang L, Ren P. 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

19. Xie M, Li Y, Cheng TO, Wang X, Dong N, Nie X 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:

20. 1016/j.ijcard.2014.10.027

21. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L 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. European Heart Journal – Cardiovascular Imaging. 2015;16(3):233–71. DOI: 10.1093/ehjci/jev014

22. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Edvardsen T et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography. 2016;29(4):277–314. DOI: 10.1016/j.echo.2016.01.011

23. Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ et al. Doppler echocardiographic index for assessment of global right ventricular function. Journal of the American Society of Echocardiography. 1996;9(6):838–47. DOI: 10.1016/S0894-7317(96)90476-9

24. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2010;23(7):685–713. DOI: 10.1016/j.echo.2010.05.010

25. Voigt J-U, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R et al. Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. European Heart Journal - Cardiovascular Imaging. 2015;16(1):1–11. DOI: 10.1093/ehjci/jeu184

26. Masuyama T, Kodama K, Kitabatake A, Sato H, Nanto S, Inoue M. Continuous-wave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary artery pressure. Circulation. 1986;74(3):484–92. DOI: 10.1161/01.CIR.74.3.484

27. Hulshof HG, Eijsvogels TMH, Kleinnibbelink G, van Dijk AP, George KP, Oxborough DL et al. Prognostic value of right ventricular longitudinal strain in patients with pulmonary hypertension: a systematic review and meta-analysis. European Heart Journal - Cardiovascular Imaging. 2019;20(4):475–84. DOI: 10.1093/ehjci/jey120

28. Motoki H, Borowski AG, Shrestha K, Hu B, Kusunose K, Troughton RW et al. Right Ventricular Global Longitudinal Strain Provides Prognostic Value Incremental to Left Ventricular Ejection Fraction in Patients with Heart Failure. Journal of the American Society of Echocardiography. 2014;27(7):726–32. DOI: 10.1016/j.echo.2014.02.007

29. Da Costa Junior AA, Ota-Arakaki JS, Ramos RP, Uellendahl M, Mancuso FJN, Gil MA 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. The International Journal of Cardiovascular Imaging. 2017;33(1):39–46. DOI: 10.1007/s10554-016-0966-1

30. Prihadi EA, van der Bijl P, Dietz M, Abou R, Vollema EM, Marsan NA 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

31. Jafari MH, Girgis H, Van Woudenberg N, Moulson N, Luong C, Fung A et al. Cardiac point-of-care to cart-based ultrasound translation using constrained CycleGAN. International Journal of Computer Assisted Radiology and Surgery. 2020;15(5):877–86. DOI: 10.1007/s11548-020-02141-y