Ross Arena, PhD, PT, FAHA
CPX for the Assessment of Pulmonary Hypertension as a Clinical Standard of Care: The Time is Now
In the United States, CPX is a clinical standard of care for patients with heart failure, being considered for transplantation, and for individuals with unexplained dyspnea upon exertion. More recently, the evidence demonstrating the clinical utility of CPX in the assessment of patients with suspected or confirmed pulmonary hypertension has grown at an impressive rate.1, 2 Patients with either primary or secondary pulmonary hypertension suffer from a host of exertion-related abnormalities related to their pathophysiologic process. While diminished aerobic capacity and dyspnea upon exertion are hallmark characteristics, they are not unique to patients with pulmonary hypertension, thereby limiting
discriminatory value. Another key pathophysiologic characteristic of pulmonary hypertension is ventilation-abnormalities within the pulmonary system. Moreover, as disease severity progresses,
ventilation-perfusion abnormalities worsen. Unlike standard exercise testing procedures, which allows for the quantification of estimated aerobic capacity limitations and the degree of dyspnea upon exertion, CPX uniquely allows for the assessment of ventilation-perfusion abnormalities. Numerous investigations
have demonstrated abnormally high VE/VCO2 and abnormally low PETCO2 accurately reflect pulmonary hypertension-induced ventilation-perfusion abnormalities. Thus, CPX is the exercise assessment of choice to quantify the pathophysiologic process unique to pulmonary hypertension. This is in addition to
the information gained on functional limitations and symptomatology. CPX data collectively provides valuable clinical information in regards to pulmonary hypertension detection, disease severity, disease progression, therapeutic efficacy and potentially prognosis. Given the current evidence supporting use of
CPX in patients with suspected or confirmed pulmonary hypertension, it may be time to consider making this assessment a clinical standard of care in this patient population.
(1) Arena R, Lavie CJ, Milani RV, Myers J, Guazzi M. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review. J Heart Lung Transplant 2010 February;29(2):159-73.
(2) Arena R, Guazzi M, Myers J, Grinnen D, Forman DE, Lavie CJ. Cardiopulmonary exercise testing in the assessment of pulmonary hypertension. Expert Rev Respir Med 2011 April;5(2):281-93.
The Current State of CPX: Using Scientific Evidence to Guide Clinical Practice
CPX technology has been available for several decades and is well recognized as the most accurate means of quantifying aerobic capacity. Moreover, CPX uniquely allows for the additional assessment of the ventilatory response to physical exertion as well as carbon dioxide production, providing for a comprehensive assessment of cardiac, pulmonary and skeletal muscle function. Despite this, utilization of CPX in appropriate clinical circumstances still appears to lag behind the robust body of scientific evidence supporting its use. An exception to this observation is in the heart failure population where CPX is a standard assessment in determining transplant candidacy. Even so, many clinicians continue to exclusively focus on peak VO2. While this long standing CPX variable is certainly important, the lack of utilization of other clinically relevant data that is readily available, such as ventilatory efficiency, weakens the prognostic and diagnostic resolution of CPX in this patient population. While these observations are somewhat disconcerting, I find there is much reason for optimism regarding the future of CPX in clinical practice, a viewpoint stemming from the science in support of this procedure. Original scientific publications continue to mount and, more recently, several highly visible reviews and scientific statements from professional organizations have been put forth in strong support of the use of CPX in appropriate clinical circumstances. Specifically, the scientific evidence and subsequent consensus statements in support of the utilization of a more comprehensive list of CPX variables in the HF population continues to grow and is starting to influence clinical practice. In addition, evidence demonstrating the potential value of CPX in other patient populations, such as those with pulmonary hypertension and suspected myocardial ischemia, is growing at an impressive rate. These newer areas of research may eventually support the expansion of CPX in clinical practice. Research into the value of CPX will certainly continue and is necessary to refine its optimal employment in clinical practice.
In parallel to ongoing research endeavours, re-examining the functionality of software packages operating CPX systems is warranted. While the large volume of exercise data provided within an automatically generated CPX report is appealing and of great interest to the research physiologist, clinicians often find this amount of data cumbersome, making it difficult to identify the variables most relevant for a particular patient undergoing this exercise assessment. Research indicates the list of highly relevant clinical variables can typically be honed down to a short list and individualized to a specific disease state or reason for testing. Moreover, threshold values with diagnostic and/or prognostic importance in a number of patient populations have been identified for several CPX variables. The inclusion of these thresholds, with automated interpretation of relevance, into standard CPX software packages would also greatly improve clinical interpretation. Admittedly, these recommended changes to software packages operating CPX systems would be a substantial paradigm shift and would require close collaboration between industry and both clinicians and scientists in the CPX community. Bringing all stakeholders together to simplify the reporting of CPX data, while simultaneously making it more specific to the patient’s condition and reason for testing, would almost certainly improve clinical acceptance and therefore utilization.
As a clinical researcher, I have devoted a majority of my career to better defining the appropriate use of CPX as well as optimizing data interpretation. Over the past 10 years, I have observed the gap between the science supporting CPX and clinical application narrow substantially. This is something I and many of my colleagues have strived for and are excited to witness the positive strides that have been made in the clinical application of CPX. Moreover, we are equally excited to see how these changes in clinical application have improved patient assessment and subsequent decisions in medical management. I have no doubt that these positive strides will continue, giving reason for those of us in the CPX community to be tremendously enthusiastic about the future.
In closing, it is a true honour to have been asked to be the correspondent for the American Chapter of CPX International. My plan is to provide regular updates on key advances made in CPX and editorials on important topics. There are countless individuals in the United States who are involved in CPX, many of whom with far greater experience and insight into this area of research and clinical practice. To that end, I welcome comments and editorials from interested individuals within the United States (please send correspondence to:email@example.com ). I would like to make this an open forum where different viewpoints and opinions are expressed. I look forward to hearing from you in the near future.
Ross Arena, PhD
Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults: a Scientific Statement from the American Heart Association
A new Scientific Statement addressing Cardiopulmonary Exercise Testing in Adults was recently published by the American Heart Association. This document takes its place next to statements previously published by the American Thoracic Society/American College of Chest Physicians and Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention[3-5] as must read material for all clinicians and researchers interested or currently involved in CPX. These statements collectively provide an excellent description of key exercise variables and summarize the evidence supporting the use of CPX in various patient populations. The new statement from the American Heart Association updates the scientific evidence supporting the use of CPX in established areas (systolic heart failure and unexplained dyspnea) as well as indentifies other patient populations where this assessment technique may be valuable, including:
- Heart Failure with Normal Ejection Fraction
- Mitochondrial Myopathy
- Exercise Prescription in Cardiac Disease and Stroke Populations
- Disability Assessment
- Adults with Congenital Heart Disease
- Pulmonary Hypertension
- Evaluation of Pacemaker Function
- Assessment of Ischemic Heart Disease
- Bariatric Surgery
The full AHA scientific statement can be found at: http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3181e52e69
1. Balady GJ, Arena R, Sietsema K,et al. Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults. A Scientific Statement From the American Heart Association. Circulation 2010;122:191-225.
2. American Thoracic Society, American College of Chest Physicians. ATS/ACCP Statement on Cardiopulmonary Exercise Testing. Am J Respir Crit Care Med 2003;167:211-277.
3. Piepoli MF, Corra U, Agostoni PG,et al. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure. Eur J Cardiovasc Prev Rehabil 2006;13:150-164.
4. Piepoli MF, Corra U, Agostoni PG,et al. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure. Eur J Cardiovasc Prev Rehabil 2006;13:300-311.
5. Piepoli MF, Corra U, Agostoni PG,et al. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part III: Interpretation of cardiopulmonary exercise testing in chronic heart failure and future applications. Eur J Cardiovasc Prev Rehabil 2006;13:485-494.
Considerations for the Physician Referring a Patient for CPX
The evidence supporting the use of CPX in appropriate clinical circumstances is unquestionably strong. However, there seems to be a lack of information on what a physician referring a patient for CPX should consider. Additionally, there does not seem to be a currently available document that concisely describes the key CPX variables a referring physician should expect in the final report and be comfortable interpreting.
Our group has recently published a review that addresses these issues.1 This document addresses:
- Patient referral and testing logistics
- Identifying an appropriate CPX laboratory for referral
- Key CPX data to be included in the final report specific to the reason for referral
A sample CPX referral form for use by the referring physician is also included.
We hope this document will be useful to physicians referring their patients for CPX.
Ross Arena, PhD
(1) Arena R, Myers J, Lavie CJ, Forman DE, Guazzi M. Ordering a cardiopulmonary exercise test for your patient: key considerations for the physician. Future Cardiol 2011;7:55-60.