Type of task force
2022 Meeting Report
Initiate a strategy for the completion of an expert consensus document establishing the definition, diagnosis, and standardised approach to treatment of exercise-induced pulmonary hypertension (PH) along with establishing recommendations for exercise testing and training.
Need for the statements:
Universally accepted methods for the assessment of exercise capacity in individuals with PH at rest or provoked by exercise are lacking. Consequently, there is substantial variability in the characterisation of the exercise-induced PH pathophenotype in clinical research and in “real world” practice. In addition, increasing reports are available characterising the consequences of routine exercise on the trajectory of pulmonary vascular disease. Taken together, the development of contemporary recommendations for the safety and potential benefits of therapeutic exercise in pulmonary vascular disease is timely.
This PVRI taskforce proposes to develop three separate guidelines on the following topics:
- Laboratory-based methods to identify and evaluate maladaptive changes to cardiopulmonary hemodynamics and right ventricular function provoked by exercise: From experimental animal models to clinical studies of exercise-induced PH patients.
- Recommendations for the standardised approach to evaluating exercise capacity in PH
- Recommendations for the safety and potential benefits of exercise training, physical activity, and participation in organised athletics in PH
- Recommendations for exercise in the design (i.e., enrichment of vascular phenotypes in Group 3 PH) and as an endpoint in clinical trials (i.e., 6 MWT vs nCPET vs iCPET)
Outcome of these Guidelines:
These Guidelines will be published in Pulmonary Circulation, which is the official record of academic reports for the PVRI. Endorsement from other key agencies will also be pursued to increase the visibility and strength of these recommendations.
Mission of Task Force:
- Definition of exercise pulmonary hypertension (ePH)
- Standardised cardiopulmonary exercise test administration, data collection and reporting
- Deep phenotyping Using Exercise Testing
What has been achieved over the years, in particular updates during the last three years.
The task force membership agreed on a broad framework of a consensus statement on exercise in pulmonary vascular disease. The document should include the following specific issues:
- Exercise PH is associated with exertional intolerance
- Exercise PH substantively affects exercise tolerance through decreases in oxygen delivery and its peripheral utilisation
- The earliest manifestations of PH are revealed through invasive cardiopulmonary exercise testing including changes in pulmonary vascular compliance, distensibility and RV:PV uncoupling
- Transpulmonary flux of biomarkers suggest ePH is associated with an early vasculopathy
- Event free survival is reduced in untreated ePH
- Treatment of ePH with pulmonary vasodilators improves symptoms, exercise capacity and long-term outcome
- Demonstrated a metabolomic plasma signature in ePH1
- Demonstrated dynamic RV/pulmonary vascular uncoupling by iCPET in ePH
- Demonstrated dynamic RV/pulmonary vascular uncoupling by iCPET in HFpEF
- Described abnormal pulmonary vascular distensibility and blood flow gradient as early findings in PAH
- Established an international registry for ePH https://ichgcp.net/clinical-trials-registry/ NCT03954574(PEXNET)
- Shown that RV imaging and exercise endpoints are important in the sub-characterisation of idiopathic PAH
- Shown that exercise endpoints can identify a low-risk phenotype among REVEAL/ERS risk score intermediate risk PAH subjects
Goals/Aims for 2022
- Further research into dynamic RV/pulmonary vascular uncoupling to exercise performance and long-term outcome
- Publication of a comprehensive and practical review on the application of exercise testing in pulmonary vascular disease to include the following:
• Methodology - Maximal invasive testing - Maximal non invasive - Submaximal
• Application of exercise testing to specific populations of patients
• Exercise testing pathway for suspected pulmonary hypertension in adults
• Exercise testing in children with suspected pulmonary hypertension
• Future directions - Coupling - Distensibility - Metabolism - Application in clinical trials - Computational models – machine learning and AI
• Conclusion and areas of research priority
2020 Annual Report
Due to the global COVID-19 pandemic, this Task Force has not been able to undertake specific activities during 2020. The Task Force leaders and many of its members were called to frontline duties caring for the sickest and most vulnerable patients. We express our sincere and heartfelt thanks to all our colleagues for their tireless and invaluable work during this crisis.
2019 Annual Report
What has been achieved/learned over the years, in particular updates during 2019
The Exercise Task Force membership agreed on a broad framework of a consensus statement on exercise pulmonary hypertension as a disease. The document outline is as follows:
- exercise pulmonary hypertension (ePH) is associated with exertional intolerance.
- ePH substantively affects exercise tolerance through decreases in oxygen delivery and its peripheral utilisation.
- the earliest manifestations of pulmonary hypertension are revealed through invasive cardiopulmonary exercise testing including changes in pulmonary vascular compliance, distensibility and right ventricular-pulmonary vascular (RV-PV) uncoupling.
- transpulmonary flux of biomarkers suggest ePH is associated with an early vasculopathy.
- event free survival is reduced and untreated ePH.
- treatment of ePH with pulmonary vasodilators improves symptoms, exercise capacity and long-term outcome.
- demonstrated a metabolomic plasma signature in ePH.1
- demonstrated dynamic right ventricular-pulmonary vascular uncoupling by iCPET in ePH.2
- demonstrated dynamic RV-PV uncoupling by iCPET in HFpEF.3
- described abnormal pulmonary vascular distensibility and blood flow gradient as early findings in pulmonary arterial hypertension.4-5
- established an international registry for ePH.
Goals/Aims for 2020/21
- Deep phenotyping of ePH, including imaging and transpulmonary flux of biomarkers (metabolomics, proteomics, transcriptomics and coagulomics).
- Further research into dynamic right ventricular-pulmonary vascular uncoupling to exercise performance and long-term outcome.
- Publication of a high impact review of exercise pulmonary hypertension.
- Sanders JL, Han Y, Urbina MF, Systrom DM, Waxman AB. Metabolomics of exercise pulmonary hypertension are intermediate between controls and patients with pulmonary arterial hypertension. Pulm Circ. 2019 Oct 30;9(4):2045894019882623.
doi: 10.1177/2045894019882623. eCollection 2019 Oct-Dec. PubMed PMID: 31695905; PubMed Central PMCID: PMC6822198.
- Singh I, Rahaghi FN, Naeije R, Oliveira RKF, Vanderpool RR, Waxman AB, Systrom
DM. Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension.
Pulm Circ. 2019 Jul-Sep;9(3):2045894019862435. doi: 10.1177/2045894019862435. PubMed PMID: 31218910; PubMed Central PMCID: PMC6643191.
- Singh I, Rahaghi FN, Naeije R, Oliveira RKF, Systrom DM, Waxman AB. Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction. Chest. 2019 Nov;156(5):933-943. doi: 10.1016/j.chest.2019.04.109. Epub 2019 May 16. PubMed PMID: 31103695.
- Singh I, Oliveira RKF, Naeije R, Rahaghi FN, Oldham WM, Systrom DM, Waxman AB. Pulmonary Vascular Distensibility and Early Pulmonary Vascular Remodeling in Pulmonary Hypertension. Chest. 2019 Oct;156(4):724-732. doi: 10.1016/j.chest.2019.04.111. Epub 2019 May 20. PubMed PMID: 31121149.
- Kohli P, Kelly VJ, Kehl EG, Rodriguez-Lopez J, Hibbert KA, Kone M, Systrom DM, Waxman AB, Venegas JG, Channick R, Winkler T, Harris RS. Perfusion Imaging Distinguishes Exercise Pulmonary Arterial Hypertension at Rest. Am J Respir Crit Care Med. 2019 Jun 1;199(11):1438-1441. doi: 10.1164/rccm.201810-1899LE. PubMed PMID: 30811948.