The Advanced Cardiopulmonary Exercise Testing (ACPET) Program at UPMC; Respiratory Reader Fall 2019

November 12, 2019

The Advanced Cardiopulmonary Exercise Testing (ACPET) Program at UPMC

by Michael G. Risbano, MD, MA, FCCP

The initial evaluation for patients referred with breathlessness or fatigue with exertion often utilizes resting diagnostic studies including echocardiography, pulmonary function tests, chest imaging, and blood work. While these tests may assist in diagnosing disease states, physiologic abnormalities and the prominence of a disease state in patients with multiple cardiopulmonary disorders often cannot be determined. Provocative testing with advanced cardiopulmonary exercise testing (ACPET) challenges the cardio-pulmonary-vascular and skeletal muscle systems to elicit a cascade of physiologic events not measurable at rest.1,2 The ACPET Program was instituted at UPMC Presbyterian Shadyside in June 2017, and since then, over 120 cases have been performed on patients with various cardiopulmonary disorders.

What Is ACPET?

Advanced cardiopulmonary exercise testing includes breath-by-breath analysis of ventilatory gas exchange and invasive measurement of pulmonary vascular and cardiac function in association with upright cycle ergometer and electrocardiogram (ECG) exercise testing.3 ACPET provides full physiologic assessment of patients referred for exertional dyspnea and fatigue. With the ACPET modality, cardiac output, pulmonary artery pressures, multiple ventilatory indices, systemic pressures, and ECG variables are simultaneously assessed during a progressive intensity exercise provocation. Performing the study in the upright, seated position on a stationary bicycle ergometer replicates daily activities as almost all efforts are performed against gravity in the upright position (see Figure 1).

ACPET 1 RR Fall 2019
Figure 1: ACPET in action in the Cardiac Cath Lab at UPMC Presbyterian.

ACPET can delineate disease states related to pulmonary arterial, pulmonary venous, cardiac valvular, loading dynamics, autonomic, and skeletal muscle pathophysiologies that limit exercise capacity. Non-invasive CPET testing can be safely performed in patients with various disease states such as pulmonary arterial hypertension;4 however, without the invasive component, the pulmonary vascular pressures and resistances, as well as cardiac output, are unknown. With ACPET, there is direct measurement of cardiopulmonary vascular hemodynamics, which provides gold standard information about hemodynamic response to exercise in conjunction with ventilatory mechanics and breath-by-breath analysis.

How Is the ACPET Performed?

ACPET at UPMC Presbyterian Shadyside involves the placement of a pulmonary artery catheter into the right internal jugular vein (see Figure 2) and a radial arterial line under ultrasound guidance in the cardiac catheterization lab. A resting supine pulmonary artery (PA) catheterization is performed to establish baseline values. The resting portion may include a shunt run or response to pulmonary vasodilators, if indicated. Once completed, the patient is seated in an upright position and cardiopulmonary hemodynamics are re-measured, as a change in body position often affects pressures, vascular resistance, and cardiac outputs. The patient is then connected to the CPET/metabolic cart, to obtain baseline resting values. Pulmonary gas exchange is measured with the Ultima™ CardiO2 gas exchange analysis system by Medical Graphics Corporation (St. Paul, Minn.).

ACPET 2 RR Fall 2019
Figure 2: Dr. Michael Risbano performing a right heart catheterization.

Shortly after, the patient is placed on the stationary bicycle in the cardiac cath lab where the stages of freewheel (no resistance applied) and four to five stages of ramped exercise are performed. The ramp chosen depends upon the patient’s demographics and level of personal fitness. Hemodynamics and blood work are obtained every two minutes during exercise. Simultaneous blood gas measurements taken from the pulmonary artery and radial artery catheter allow for measurement of direct Fick cardiac output as well as oxygen saturations and lactate levels. We routinely calculate oxygen content from the pulmonary artery and radial artery to assess for peripheral oxygen extraction. Patients exercise until limited by symptoms of fatigue, leg fatigue, dyspnea, chest pain, or a combination of these symptoms. If a patient is not limited by symptoms, the study is completed after eight to 12 minutes of exercise, preferably a peak exercise study. Finally, a cool down is done and recovery hemodynamics are measured.

Pulmonary arterial hypertension is defined as a resting mean PA pressure (mPAP) >25 mmHg and pulmonary vascular resistance (PVR) >3.0 Wood units (WU). Normal resting hemodynamics are mPAP <25 mmHg and PVR <3.0 WU. We define exercise pulmonary arterial hypertension while upright as mPAPpeak >30 mmHg, total pulmonary resistance (TPRpeak) >3.0 WU with a pulmonary arterial wedge pressure (PAWP) peak <20 mmHg. If the PAWPpeak is >20 mmHg, this constitutes an abnormal pulmonary venous response to exercise and may indicate heart failure with preserved ejection fraction (EF) in patients with a normal EF percentage and no valvular disease.

Indications for ACPET Referrals and Patient Populations of Interest

Patients referred for ACPET will include those with complaints of dyspnea on exertion or exercise fatigue that has not been fully explained by previous studies, or the causative disease state is unclear. The majority of patients referred to the ACPET Program will have been seen by either a primary care physician or a subspecialty physician, such as a pulmonologist, cardiologist, rheumatologist, or geriatrician.

Patients referred for testing may include those with dyspnea and histories of connective tissue disease (scleroderma in particular), diastolic dysfunction (heart failure with preserved ejection fraction), pre-pulmonary or pre-cardiac transplant, valvular heart disease, post-pulmonary embolism, parenchymal lung disease (interstitial lung disease, chronic obstructive pulmonary disease, cystic fibrosis), peripheral myopathy, and various forms of pulmonary hypertension, including pulmonary arterial hypertension.

Initial routine testing is required prior to performing ACPET including echocardiogram, pulmonary function testing, and chest imaging. As previously mentioned, for some patients these tests may be unrevealing or may demonstrate multiple abnormalities such as concomitant lung disease and pulmonary hypertension or diastolic dysfunction. This technique provides a comprehensive ACPET to study and diagnose all forms of abnormal cardiopulmonary vascular and musculoskeletal responses to exercise for clinical and research purposes.

Impact of the ACPET Program

In a single-center study that performed a high volume of ACPETs, the authors demonstrated that the workup of exertional dyspnea in a multidisciplinary setting including ACPET dramatically reduced the time to diagnosis compared to routine testing alone.5 Typical diagnoses made with the study include exercise pulmonary arterial hypertension, exercise pulmonary venous hypertension, ventilatory limitation, oxidative myopathy, and dysautonomia/preload insufficiency.6

Key benefits of ACPET include:

  • Diagnosis of the etiology of exercise limitation or dyspnea on exertion not previously identified
  • Development of a plan for intervention that may include pharmacologic, surgical, or cardiac/pulmonary rehabilitation therapies
  • Identification of patients who may be eligible for clinical treatment trials or participation in investigational research trials

Our notable accomplishments include:

  • Successful diagnosis of patients with exercise PAH with provocative exercise testing and treatment with pulmonary vasodilators, which resulted in reduced pulmonary vascular response to exercise and improved cardiac outputs with exercise.7
  • Identification of an abnormal pulmonary vascular response to exercise in patients with chronic thromboembolic pulmonary disease, which led to successful treatment with balloon pulmonary angioplasty
  • Diagnosis of a patient with cystic fibrosis using ACPET, which ultimately led to a successful lung transplant.

Commercial insurance typically covers the ACPET study.

Referral Information

For any patients who have continued dyspnea despite comprehensive testing and interventions, referrals can be made by calling 1-877-PH4-UPMC or emailing

Referrals can also be made to Dr. Risbano directly at

For more information about the ACPET Program, including patient information and frequently asked questions, please visit our website at


  1. Hasler ED, Muller-Mottet S, Furian M, et al. “Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.” Chest. 2016;150:57-67.
  2. Correale M, Tricarico L, Ferraretti A, et al. “Cardiopulmonary exercise test predicts right heart catheterization.” Eur J Clin Invest. 2017;47.
  3. Berry NC, Manyoo A, Oldham WM, et al. “Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice.” Pulm Circ. 2015;5:610-8.
  4. Weatherald J, Farina S, Bruno N, Laveneziana P. “Cardiopulmonary Exercise Testing in Pulmonary Hypertension.” Ann Am Thorac Soc. 2017;14:S84-S92.
  5. Huang W, Resch S, Oliveira RK, Cockrill BA, Systrom DM, Waxman AB. “Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center.” Eur J Prev Cardiol. 2017;24:1190-9.
  6. Oldham WM, Lewis GD, Opotowsky AR, Waxman AB, Systrom DM. “Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing.” Pulm Circ. 2016;6:55-62.
  7. Wallace WD, Nouraie M, Chan SY, Risbano MG. “Treatment of exercise pulmonary hypertension improves pulmonary vascular distensibility.” Pulm Circ. 2018;8:2045894018787381.