A Heartful Research Experience: The Effect of Exercise on Pulmonary Hypertension
By: Elizabeth Karvasarski
Supervisors: Dr. Susanna Mak and Dr. Stephen Wright
Many patients with pulmonary hypertension, or high blood pressure in the lungs, experience debilitating breathlessness and exercise intolerance. Pulmonary hypertension can be classified as pulmonary arterial hypertension (PAH), which is related to narrowing of the lung vasculature, or due to downstream left heart disease (PH-LHD). PAH affects tens of thousands of Canadians while heart failure affects over 500,000, nearly half of whom have PH-LHD.1
In 2015, I had a co-op student opportunity in the Mount Sinai Hospital Cardiac Catheterization Clinical Research Laboratory. I was intrigued that the lab was studying how blood pressure and flow in the lungs normally responded to exercise in healthy adults, since it complemented my kinesiology background. This experience drove my interest in cardiovascular physiology, and this year, I was invited to participate in the IMS Summer Undergraduate Research Program and again work in Dr. Susanna Mak’s laboratory.
I joined the team working on The BREATH Program, with the mentorship of Dr. Stephen Wright, a recent graduate of the IMS PhD program. Right heart catheterization is the gold-standard approach to diagnosis pulmonary hypertension. However, it can be challenging to diagnosis pulmonary hypertension and determine whether it is PAH or PH-LHD from resting measurements for some patients with exercise intolerance, particularly early in the disease. The BREATH Program, which was developed from the research I observed during my earlier experience2 and supported by a Peter Munk Cardiac Centre Innovation Award, uses exercise to reveal abnormal hemodynamic responses during right heart catheterization. This is valuable for patients who experience breathlessness and exercise intolerance but have unremarkable resting cardiac and respiratory tests3.
We hypothesized that the pattern of the pulmonary artery pressure response to exercise over time provides information that may discriminate abnormal from normal and PAH from PH-LHD. We focused on pulmonary artery diastolic pressure (PADP) when the heart is relaxed, which can be influenced by either pulmonary vasoconstriction or left heart dysfunction, and the pulse pressure (PP), which reflects vascular stiffness and the stroke volume that is input by cardiac contraction. I studied 53 patients divided into three groups (Normal, PAH, and PH-LHD) and measured PADP and PP every 30 sec from rest through exercise to characterize their responses. While PADP increased slightly and plateaued beyond 2 min. in Normal patients, it continued to rise for 5 min. in patients with PAH or PH-LHD. Additionally, while both Normal and PH-LHD patients had similar PP increases with exercise, in PAH the increase was nearly doubled which may reflect that they have a smaller pulmonary reserve to accommodate increased blood flow.
This study demonstrated that exercise reveals PADP and PP responses that can serve to differentiate the physiology of PAH and PH-LHD, which can be challenging to determine for some patients who have exercise intolerance. The SURP program has given me an amazing research experience leading my own project, and how to disseminate knowledge through an abstract and poster presentation. I hope to be able to apply what I have learned this summer and continue making contributions to science.
- Tampakakis E, Leary PJ, Selby VN, Marco TD, Cappola TP, Felker GM, et al. The Diastolic Pulmonary Gradient Does Not Predict Survival in Patients With Pulmonary Hypertension Due to Left Heart Disease. JACC: Heart Failure. 2015;3(1):9–16.
- Wright SP, Esfandiari S, Gray T, Fuchs FC, Chelvanathan A, Chan W, et al. The pulmonary artery wedge pressure response to sustained exercise is time-variant in healthy adults. Heart. 2016;102(6):438–43.
- 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. European Journal of Preventive Cardiology. 2017;24(11):1190–9.