MRI assessment of aortic flow in patients with pulmonary arterial hypertension in response to exercise

Abstract

Background: While primarily a right heart disease, pulmonary arterial hypertension (PAH) can impact left heart function and aortic flow through a shifted interventricular septum from right ventricular pressure overload and reduced left ventricular preload, among other mechanisms. In this study, we used phase contrast (PC) MRI and a modest exercise challenge to examine the effects of PAH on systemic circulation. While exercise challenges are typically performed with ultrasound in the clinic, MRI exercise studies allow for more reproducible image alignment, more accurate flow quantification, and improved tissue contrast.

Methods: Six PAH patients and fifteen healthy controls (8 older age-matched, 7 younger) exercised in the magnet bore with an MRI-compatible exercise device that allowed for scanning immediately following cessation of exercise. PC scans were performed in the ascending aorta during a breath hold immediately after modest exercise to non-invasively measure stroke volume (SV), cardiac output (CO), aortic peak systolic flow (PSF), and aortic wall stiffness via relative area change (RAC).

Results: Images following exercise showed mild blurring, but were high enough quality to allow for segmentation of the aorta. While SV was approximately 30% lower in PAH patients (SVPAH,rest = 67 ± 16 mL; SVPAH,stress = 90 ± 42 mL) than age-matched controls (SV,older,rest = 93 ± 16 mL; SVolder,stress = 133 ± 40 mL) at both rest and following exercise, CO was similar for both groups following exercise (COPAH,stress = 10.8 ± 5.7 L/min; COolder,stress = 11.8 ± 5.0 L/min). This was achieved through a compensatory increase in heart rate in the PAH subjects (74% increase as compared to 29% in age-matched controls). The PAH subjects also demonstrated reduced aortic peak systolic flow relative to the healthy controls (PSFPAH,rest = 309 ± 52 mL/s; PSFolder,rest = 416 ± 114 mL/s; PSFPAH,stress = 388 ± 113 mL/s; PSFolder,stress = 462 ± 176 mL/s). PAH patients and older controls demonstrated stiffer aortic walls when compared to younger controls (RACPAH,rest = 0.15 ± 0.05; RAColder,rest = 0.17 ± 0.05; RACyoung,rest = 0.28 ± 0.08).

Conclusions: PC MRI following a modest exercise challenge was capable of detecting differences in left heart dynamics likely induced from PAH. These results demonstrated that PAH can have a significant influence on systemic flow, even when the patient has no prior left heart disease. Image quantification following exercise could likely be improved in future studies through the implementation of free-breathing or real-time MRI acquisitions.

Trial registration: Retrospectively registered on 02/26/2018 (TRN: NCT03523910 ).

Keywords: Exercise; Flow; MRI; Pulmonary arterial hypertension; Stress test.

Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Before participation in the study, written informed consent was obtained from all individual subjects to participate in study activities and use their data in a research capacity. This study was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board (IRB 2011–0980; PI: Francois).

Consent for publication

Not applicable.

Competing interests

The University of Wisconsin receives research support from GE Healthcare. The authors declare that they have no other potential competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

MRI-compatible exercise device. The subject exercises in the magnet bore via a dynamic stepping motion to the beat of a metronome. Resistance is controlled by removable weights at the end of each lever

Fig. 2

Exercise and imaging paradigm for all three groups. PC imaging was performed in the ascending aorta at rest prior to exercise. This was followed by 3 min of exercise at a power of 30 W. An identical PC scan to that performed at rest immediately followed the end of exercise

Fig. 3

Representative magnitude PC image quality in the ascending aorta (a) at rest and (b) immediately following exercise. Mild blurring was observed in images following exercise alongside some darkening of the blood, but image quality was still sufficient to delineate relevant vasculature

Fig. 4

Boxplots displaying the distribution of key aortic flow variables as measured with PC MRI in the ascending aorta: (a) stroke volume, (b) cardiac output, (c) peak systolic velocity, and (d) peak systolic flow. Blue indicates young controls, green indicates older controls, and red represents PH subjects. A bracket between two boxplots indicates a statistically significant (p < 0.05) difference between the two groups of measurements

Fig. 5

Distribution of aortic wall stiffness as calculated with the relative area change method in the ascending aorta. Blue indicates young controls, green indicates older controls, and red represents PH subjects. A bracket between two boxplots indicates a statistically significant (p < 0.05) difference between the two groups of measurements