Cardiopulmonary exercise testing for treatment effect assessment in chronic thromboembolic pulmonary hypertension patients

Aim      To determine possibilities of the cardiopulmonary stress test (CPST) as an unbiassed, noninvasive method for evaluation of the effect of managing patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Material and methods  This study included 37 patients with CTEPH, 24 men (mean age, 53±15 years) and 13 women (mean age, 58±8.5 years). The diagnosis was verified and theCoperability was assessed according to 2015 European Society of Cardiology Clinical Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension (PH). The surgical treatment was used in 65 % (n=24) of CTEPH patients: the group with pulmonary thromboendarterectomy constituted 35 % (n=13); the group with balloon pulmonary angioplasty 30% (n=11); and the conservative tactics was used in 27 % (n=10) of patients.

Results Baseline CPST parameters significantly correlated with parameters of right heart catheterization (RHC): mixed venous oxygen saturation (SvO2) significantly positively correlated with V´O2peak (r=0.640, p<0.05), V´O2 / heart rate (HR) (r=0.557; p<0.001), PETCO2 peak (r=0.598, p<0.05), and V´E / V´CO2 (r=0.587; p<0.001); cardiac output (CO) correlated with V´O2 / HR (r=0.555, p<0.001), PETCO2peak (r= –0.476; p<0.05 and r=0.555, p<0.001 for ´E / V´CO2). In repeated testing, the physical working capacity (V´O2peak) increased only in patients after the surgical treatment of CTEPH. Importantly in this process, significant correlations remained between a number of CPST and RHC parameters: SvO2 correlated with V´O2peak (r=0.743; p<0.05), V´O2 /HR (r=0.627; p<0.001), PETCO2peak (r=0.538; p<0.05), and V´E / V´CO2 (r=0.597; p<0.001); V´O2 / HR, PETCO2peak, and V´E / V´CO2 significantly correlated with CO (r=0.645, p<0.001; r= –0.516, p<0.001, and r=0.555, p<0.001, respectively.

Conclusion      CPST can be used as a noninvasive instrument for evaluation of the effect of CTEPH treatment, particularly in the absence of echocardiographic data for residual PH.

1. Ministry of Health of Russian Federation. Pulmonary hypertension, including chronic thromboembolic pulmonary hypertension. Av. at: https://scardio.ru/content/Guidelines/2020/Clinic_rekom_LG.pdf.

2. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A 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). European Heart Journal. 2016;37(1):67–119. DOI: 10.1093/eurheartj/ehv317

3. Barco S, Russo M, Vicaut E, Becattini C, Bertoletti L, Beyer-Westendorf J et al. Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Clinical Research in Cardiology. 2019;108(7):772–8. DOI: 10.1007/s00392-018-1405-1

4. Stevens H, Fang W, Clements W, Bloom J, McFadyen J, Tran H. Risk Stratification of Acute Pulmonary Embolism and Determining the Effect on Chronic Cardiopulmonary Complications: The REACH Study. TH Open. 2020;04(01):e45–50. DOI: 10.1055/s-0040-1708558

5. Klok FA, van Kralingen KW, van Dijk APJ, Heyning FH, Vliegen HW, Huisman MV. Prospective cardiopulmonary screening program to detect chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Haematologica. 2010;95(6):970–5. DOI: 10.3324/haematol.2009.018960

6. Simonneau G, Torbicki A, Dorfmüller P, Kim N. The pathophysiology of chronic thromboembolic pulmonary hypertension. European Respiratory Review. 2017;26(143):160112. DOI: 10.1183/16000617.0112-2016

7. Chazova I.E., Martynyuk T.V., Valieva Z.S., Nakonechnikov S.N., Nedogoda S.V., Salasyuk A.S. et al. The economic burden of chronic thromboembolic pulmonary hypertension in Russian Federation. Therapeutic Archive. 2018;90(9):101–9. DOI: 10.26442/terarkh2018909101-109

8. Chernyavsky A.M., Edemsky A.G., Chernyavsky M.A., Tarkova A.R., Efimenko V.G., Ivanov S.N. Five-year results of surgical treatment of patients with chronic postembolic pulmonary hypertension. Translational Medicine. 2014;2:72–7.

9. Pepke-Zaba J, Delcroix M, Lang I, Mayer E, Jansa P, Ambroz D et al. Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Results From an International Prospective Registry. Circulation. 2011;124(18):1973–81. DOI: 10.1161/CIRCULATIONAHA.110.015008

10. Madani M, Mayer E, Fadel E, Jenkins DP. Pulmonary Endarterectomy. Patient Selection, Technical Challenges, and Outcomes. Annals of the American Thoracic Society. 2016;13(Suppl 3):S240–7. DOI: 10.1513/AnnalsATS.201601-014AS

11. Cannon JE, Su L, Kiely DG, Page K, Toshner M, Swietlik E et al. Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort. Circulation. 2016;133(18):1761–71. DOI: 10.1161/CIRCULATIONAHA.115.019470

12. Ogawa A, Matsubara H. Balloon Pulmonary Angioplasty: A Treatment Option for Inoperable Patients with Chronic Thromboembolic Pulmonary Hypertension. Frontiers in Cardiovascular Medicine. 2015;2:4. DOI: 10.3389/fcvm.2015.00004

13. Lang I, Meyer BC, Ogo T, Matsubara H, Kurzyna M, Ghofrani H-A et al. Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. European Respiratory Review. 2017;26(143):160119. DOI: 10.1183/16000617.0119-2016

14. Olsson KM, Wiedenroth CB, Kamp J-C, Breithecker A, Fuge J, Krombach GA et al. Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience. European Respiratory Journal. 2017;49(6):1602409. DOI: 10.1183/13993003.02409-2016

15. Simakova M.A., Moiseeva O.M. Soluble Guanylate Cyclase Stimulators for Chronic Thromboembolic Pulmonary Hypertension Patients Treatment: New Data. Rational Pharmacotherapy in Cardiology. 2020;16(2):317–23. DOI: 10.20996/1819-6446-2020-04-13

16. 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

17. ATS Statement: Guidelines for the Six-Minute Walk Test. American Journal of Respiratory and Critical Care Medicine. 2002;166(1):111–7. DOI: 10.1164/ajrccm.166.1.at1102

18. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M et al. Clinical Correlates and Prognostic Significance of Six-minute Walk Test in Patients with Primary Pulmonary Hypertension: Comparison with Cardiopulmonary Exercise Testing. American Journal of Respiratory and Critical Care Medicine. 2000;161(2):487–92. DOI: 10.1164/ajrccm.161.2.9906015

19. Savarese G, Paolillo S, Costanzo P, D’Amore C, Cecere M, Losco T et al. Do Changes of 6-Minute Walk Distance Predict Clinical Events in Patients With Pulmonary Arterial Hypertension? Journal of the American College of Cardiology. 2012;60(13):1192–201. DOI: 10.1016/j.jacc.2012.01.083

20. Berezina A.V., Kozlenok A.V. The cardiopulmonary test in the cardiology. Translational Medicine. 2014;2:13–7.

21. Held M, Grün M, Holl R, Hübner G, Kaiser R, Karl S et al. Cardiopulmonary Exercise Testing to Detect Chronic Thromboembolic Pulmonary Hypertension in Patients with Normal Echocardiography. Respiration. 2014;87(5):379–87. DOI: 10.1159/000358565

22. Ruigrok D, Symersky P, Nossent EJ, Boonstra A, Vonk Noordegraaf A, Meijboom LJ et al. An observational analysis of exercise capacity in CTEPH patients after pulmonary endarterectomy. European Respiratory Journal. 2019;54(Suppl 63):OA5163. DOI: 10.1183/13993003.congress-2019.OA5163

23. Hoole SP, Coghlan JG, Cannon JE, Taboada D, Toshner M, Sheares K et al. Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: the UK experience. Open Heart. 2020;7(1):e001144. DOI: 10.1136/openhrt-2019-001144

24. Jin Q, Luo Q, Yang T, Zeng Q, Yu X, Yan L et al. Improved hemodynamics and cardiopulmonary function in patients with inoperable chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty. Respiratory Research. 2019;20(1):250. DOI: 10.1186/s12931-019-1211-y