Exercise feature and predictor of prognosis in patients with pulmonary artery stenosis-associated pulmonary hypertension

Xin Li, Anqi Duan, Qi Jin, Yi Zhang, Qin Luo, Qing Zhao, Lu Yan, Zhihua Huang, Meixi Hu, Changming Xiong, Zhihui Zhao, Zhihong Liu, Xin Li, Anqi Duan, Qi Jin, Yi Zhang, Qin Luo, Qing Zhao, Lu Yan, Zhihua Huang, Meixi Hu, Changming Xiong, Zhihui Zhao, Zhihong Liu

Abstract

Aims: The prognosis is poor for patients with pulmonary artery stenosis-associated pulmonary hypertension (PAS-PH). Identifying predictors of prognosis in PAS-PH is crucial to preventing premature death, which has rarely been investigated. We aimed to explore the cardiopulmonary exercise testing (CPET) parameters to predict the prognosis of these patients.

Methods: We prospectively included all patients with PAS-PH who underwent CPET between September 2014 and June 2021 in Fuwai Hospital (ClinicalTrials.gov ID: NCT02061787). The primary outcome was clinical worsening, including death, rehospitalization for heart failure, or deterioration of PH.

Results: Seventy-two patients were included in this study. A median of 2-year follow-up revealed that 18 (25%) patients experienced clinical worsening. The 1-year, 3-year, and 5-year event-free survival rates were 92.5%, 81.7%, and 62.7%, respectively. Patients with clinical worsening demonstrated significantly worse baseline haemodynamics and poorer exercise capacity than their counterparts. Multivariable Cox regression identified that peak O2 pulse could independently predict clinical worsening [hazard ratio: 0.344, 95% confidence interval (CI) 0.188-0.631, P < 0.001], outperforming other parameters. Peak O2 pulse correlated with PH severity. Incorporating peak O2 pulse into the simplified 2015 European Society of Cardiology/European Respiratory Society risk stratification improved the accuracy for predicting clinical worsening (pre vs. post area under the curve: 0.727 vs. 0.846, P < 0.001; net reclassification index: 0.852, 95% CI 0.372-1.332, P < 0.001; integrated discrimination index 0.133, 95% CI 0.031-0.235, P = 0.011).

Conclusions: The prognosis is poor for PAS-PH, and exercise intolerance and ventilation inefficiency are commonly observed. Peak O2 pulse independently predicted the prognosis of these patients. A low peak O2 pulse identified patients at high risk of clinical deterioration and served for risk stratification of PAS-PH.

Keywords: Cardiopulmonary exercise testing; Peak O2 pulse; Pulmonary artery stenosis; Pulmonary hypertension; Takayasu arteritis.

Conflict of interest statement

None declared.

© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1
Figure 1
Receiver operator characteristic curve of CPET parameters in predicting clinical worsening in PAS‐PH. AUC, area under the curve; CircP, circulatory power; CPET, cardiopulmonary exercise testing; OUES, oxygen uptake efficiency slope; PAS‐PH, pulmonary arterial stenosis‐associated pulmonary hypertension; VO2, oxygen uptake.
Figure 2
Figure 2
Association between the peak O2 pulse and clinical worsening of PAS‐PH patients. CI, confidence interval; HR, hazard ratio; PAS‐PH, pulmonary arterial stenosis associated pulmonary hypertension.
Figure 3
Figure 3
Kaplan–Meier event‐free survival curves based on the optimal cut‐off of the peak O2 pulse.
Figure 4
Figure 4
Receiver operator characteristic curve of the abbreviated version of the 2015 ESC/ERS PH risk stratification and the combined risk stratification strategy. AUC, area under the curve; CI, confidence interval. DeLong test pairwise comparison: Combined model vs. abbreviated version of the 2015 ESC/ERS PH risk stratification P < 0.001. Abbreviated version of the 2015 ESC/ERS PH risk stratification vs. peak O2 pulse P = 0.090. Peak O2 pulse vs. combined model P = 0.424.

References

    1. Castañer E, Gallardo X, Rimola J, Pallardó Y, Mata JM, Perendreu J, Martin C, Gil D. Congenital and acquired pulmonary artery anomalies in the adult: Radiologic overview. Radiographics. 2006; 26: 349–371.
    1. Tonelli AR, Ahmed M, Hamed F, Prieto LR. Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in adults. Pulm Circ. 2015; 5: 204–210.
    1. Bergersen L, Gauvreau K, Justino H, Nugent A, Rome J, Kreutzer J, Rhodes J, Nykanen D, Zahn E, Latson L, Moore P, Lock J, Jenkins K. Randomized trial of cutting balloon compared with high‐pressure angioplasty for the treatment of resistant pulmonary artery stenosis. Circulation. 2011; 124: 2388–2396.
    1. Zhang J, Wang P, Qin C, Zhang L, Huang D, Li Y, Xie M. ANCA (antineutrophil cytoplasmic antibody)‐associated pulmonary Vasculitis causing pulmonary artery stenosis: The value of multimodality imaging in the clinical workup. Circ Cardiovasc Imaging. 2021; 14: e012484.
    1. Seckeler MD, Pineda J, Lotun K. Successful transcatheter recanalization of a chronically occluded left pulmonary artery due to fibrosing mediastinitis. JACC Cardiovasc Interv. 2021; 14: e215–e216.
    1. Razavi H, Stewart SE, Xu C, Sawada H, Zarafshar SY, Taylor CA, Rabinovitch M, Feinstein JA. Chronic effects of pulmonary artery stenosis on hemodynamic and structural development of the lungs. Am J Physiol Lung Cell Mol Physiol. 2013; 304: L17–L28.
    1. He Y, Lv N, Dang A, Cheng N. Pulmonary artery involvement in patients with Takayasu arteritis. J Rheumatol. 2020; 47: 264–272.
    1. Yang L, Zhang H, Jiang X, Zou Y, Qin F, Song L, Guan T, Wu H, Xu L, Liu Y, Zhou X, Bian J, Hui R, Zheng D. Clinical manifestations and longterm outcome for patients with Takayasu arteritis in China. J Rheumatol. 2014; 41: 2439–2446.
    1. Toledano K, Guralnik L, Lorber A, Ofer A, Yigla M, Rozin A, Markovits D, Braun‐Moscovici Y, Balbir‐Gurman A. Pulmonary arteries involvement in Takayasu's arteritis: Two cases and literature review. Semin Arthritis Rheum. 2011; 41: 461–470.
    1. Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation. 2001; 104: 429–435.
    1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M, ESC Scientific Document Group . 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 Heart J. 2016; 37: 67–119.
    1. Jin Q, Li X, Zhang Y, Zhao Z, Zhao Q, Yan L, Duan A, Luo Q, Liu Z. Heart rate recovery at 1 min after exercise is a marker of disease severity and prognosis in chronic thromboembolic pulmonary hypertension. Respiration. 2021; 1‐10: 455–464.
    1. Tang Y, Yao L, Liu Z, Xie W, Ma X, Luo Q, Zhao Z, Huang Z, Gao L, Jin Q, Yu X, Xiong C, Ni X, Yan Y, Qi W. Peak circulatory power is a strong prognostic factor in patients with idiopathic pulmonary arterial hypertension. Respir Med. 2018; 135: 29–34.
    1. Tang Y, Luo Q, Liu Z, Ma X, Zhao Z, Huang Z, Gao L, Jin Q, Xiong C, Ni X. Oxygen uptake efficiency slope predicts poor outcome in patients with idiopathic pulmonary arterial hypertension. J Am Heart Assoc. 2017; 6: e005037.
    1. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW Jr, Masi AT, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990; 33: 1129–1134.
    1. Sharma BK, Jain S, Suri S, Numano F. Diagnostic criteria for Takayasu arteritis. Int J Cardiol. 1996; 54: S141–S147.
    1. Zhang Y, Jin Q, Zhao Z, Zhao Q, Yu X, Yan L, Li X, Duan A, An C, Ma X, Xiong C, Luo Q, Liu Z. Carbohydrate antigen 125 is a biomarker of the severity and prognosis of pulmonary hypertension. Front Cardiovasc Med. 2021; 8: 699904.
    1. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984; 70: 657–662.
    1. Callan P, Clark AL. Right heart catheterisation: Indications and interpretation. Heart. 2016; 102: 147–157.
    1. Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, Olsson KM, Meyer K, Vizza CD, Vonk‐Noordegraaf A, Distler O, Opitz C, Gibbs JSR, Delcroix M, Ghofrani HA, Huscher D, Pittrow D, Rosenkranz S, Grünig E. Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017; 50: 1700740.
    1. Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV, American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology , Council on Epidemiology and Prevention , Council on Peripheral Vascular Disease , Interdisciplinary Council on Quality of Care and Outcomes Research . Clinician's guide to cardiopulmonary exercise testing in adults: A scientific statement from the American Heart Association. Circulation. 2010; 122: 191–225.
    1. Weber KT, Janicki JS, McElroy PA. Determination of aerobic capacity and the severity of chronic cardiac and circulatory failure. Circulation. 1987; 76: Vi40–Vi45.
    1. Wang X, Dang A, Chen B, Lv N, Liu Q. Takayasu arteritis‐associated pulmonary hypertension. J Rheumatol. 2015; 42: 495–503.
    1. Hiremath G, Qureshi AM, Meadows J, Aggarwal V. Treatment approach to unilateral branch pulmonary artery stenosis. Trends Cardiovasc Med. 2021; 31: 179–184.
    1. Godinas L, Sattler C, Lau EM, Jaïs X, Taniguchi Y, Jevnikar M, Weatherald J, Sitbon O, Savale L, Montani D, Simonneau G, Humbert M, Laveneziana P, Garcia G. Dead‐space ventilation is linked to exercise capacity and survival in distal chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant. 2017; 36: 1234–1242.
    1. Accalai E, Vignati C, Salvioni E, Pezzuto B, Contini M, Cadeddu C, Meloni L, Agostoni P. Non‐invasive estimation of stroke volume during exercise from oxygen in heart failure patients. Eur J Prev Cardiol. 2021; 28: 280–286.
    1. Arena R, Myers J, Harber M, Wisloff U, Stensvold D, Kaminsky LA. Peak oxygen pulse responses during maximal cardiopulmonary exercise testing: Reference standards from FRIEND (fitness registry and the importance of exercise: An international database). Int J Cardiol. 2020; 301: 180–182.
    1. Naeije R, Badagliacca R. The overloaded right heart and ventricular interdependence. Cardiovasc Res. 2017; 113: 1474–1485.
    1. Badagliacca R, Papa S, Valli G, Pezzuto B, Poscia R, Manzi G, Giannetta E, Sciomer S, Palange P, Naeije R, Fedele F, Vizza CD. Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension. Chest. 2016; 150: 1313–1322.
    1. Laukkanen JA, Araújo CGS, Kurl S, Khan H, Jae SY, Guazzi M, Kunutsor SK. Relative peak exercise oxygen pulse is related to sudden cardiac death, cardiovascular and all‐cause mortality in middle‐aged men. Eur J Prev Cardiol. 2018; 25: 772–782.
    1. Groepenhoff H, Vonk‐Noordegraaf A, van de Veerdonk MC, Boonstra A, Westerhof N, Bogaard HJ. Prognostic relevance of changes in exercise test variables in pulmonary arterial hypertension. PLoS ONE. 2013; 8: e72013.
    1. Peterman JE, Harber MP, Chaudhry S, Arena R, Kaminsky LA. Peak oxygen pulse and mortality risk in healthy women and men: The Ball State adult fitness longitudinal lifestyle study (BALL ST). Prog Cardiovasc Dis. 2021; 68: 19–24.
    1. Ramos RP, Ota‐Arakaki JS, Alencar MC, Ferreira EV, Nery LE, Neder JA. Exercise oxygen uptake efficiency slope independently predicts poor outcome in pulmonary arterial hypertension. Eur Respir J. 2014; 43: 1510–1512.
    1. Zhai Z, Murphy K, Tighe H, Wang C, Wilkins MR, Gibbs JSR, Howard LS. Differences in ventilatory inefficiency between pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Chest. 2011; 140: 1284–1291.
    1. Charalampopoulos A, Gibbs JSR, Davies RJ, Gin‐Sing W, Murphy K, Sheares KK, Pepke‐Zaba J, Jenkins DP, Howard LS. Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension. J Appl Physiol. 2016; 121: 623–628.
    1. Klaassen SHC, Liu LCY, Hummel YM, Damman K, van der Meer P, Voors AA, Hoendermis ES, van Veldhuisen DJ. Clinical and hemodynamic correlates and prognostic value of VE/VCO slope in patients with heart failure with preserved ejection fraction and pulmonary hypertension. J Card Fail. 2017; 23: 777–782.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir