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Right Ventricular Perfusion Reserve Predicts Response to Pulmonary Thromboendarterectomy1Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States, 2Division of Cardiology, Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States, 3Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States, 4Division of Cardiac Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States, 5Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States, 6Department of Biomedical Engineering, Northwestern University, Evanston, IL, United States
Synopsis
Keywords: Heart Failure, Heart, Right Heart Failure, Cardiac Perfusion
Motivation: Little is known about the right ventricular (RV) perfusion reserve in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and whether pulmonary thromboendarterectomy (PTE) surgery improves RV perfusion.
Goal(s): This study sought to assess whether PTE improves RV perfusion in CTEPH patients and whether RV perfusion reserve correlates with invasive pulmonary hemodynamics.
Approach: We prospectively enrolled 6 CTEPH subjects undergoing PTE, performed stress-rest MRI and right heart catheterization, and calculated RV myocardial perfusion reserve pre and post PTE.
Results: RV perfusion reserve is improved in CTEPH with PTE, correlates with invasive pulmonary hemodynamics, and may serve as a non-invasive marker for monitoring treatment efficacy.
Impact: This study demonstrates feasibility of utilizing right ventricular perfusion reserve as an imaging marker for evaluation of pulmonary thromboendarterectomy (PTE) in chronic thromboembolic pulmonary hypertension (CTEPH) patients.
Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe form of pulmonary hypertension (PH)1. Right ventricular (RV) ischemia and correlations between MRI derived RV myocardial perfusion reserve (MPR) and invasive pulmonary hemodynamics produced by right heart catheterization (RHC) and RV function were observed in PH patients2. However, there is a gap in knowledge on whether similar patterns exist in CTEPH patients, and how the pulmonary thromboendarterectomy (PTE), the established gold standard treatment for CTEPH, affects RV perfusion reserve. In this study, we sought to determine whether RV perfusion reserve is reduced in patients with CTEPH, evaluate the effects of PTE on RV perfusion reserve and assess the correlations between RV perfusion reserve and invasive pulmonary hemodynamics and RV functions.Methods
Human Subjects & Pulse Sequence: We prospectively enrolled 6 CTEPH subjects (60±10 years, 4 males) undergoing PTE and performed a stress-rest (10 min apart; 0.1 mmol/kg of gadobutrol per scan) protocol at two time points (pre and post-PTE) using an accelerated pulse sequence with radial k-space sampling3. Relevant imaging parameters included: spatial resolution = 2x2 mm2, slice thickness = 8 mm, TE/TR=1.5/2.8 ms, flip angle = 15°, minimum TS = 10 ms, 42 radial spokes per frame (corresponding to an acceleration factor of 4.6). As a control group, we retrospectively identified 8 patients (49±12 years, 5 males) who underwent an identical stress-rest CMR protocol with negative coronary artery disease workup.Image reconstruction and quantification: As shown in Figure 1, both the AIF and myocardial wall images were reconstructed using a compressed sensing framework, as previously described4. Pixel-wise stress-rest myocardial blood flow (MBF) maps and the corresponding MPR were quantified for the RV free wall using the following steps (Figure 1): motion correction5, signal normalization by the proton density weighted image, signal to T1 conversion based on the Bloch equation6, T1 to gadolinium concentration ([Gd]) conversion assuming fast water exchange7, T2* correction to the AIF8, [Gd] to MBF conversion based on a Fermi model9, rate pressure product normalization for resting MBF, and MPR calculation as the ratio of mean stress and rest MBFs. We measured RV functional parameters (RVEDV [end diastolic volume], RVESV [end systolic volume], RVSV [stroke volume], RVEF [ejection fraction]) based on clinical standard cine images. Cardiac contours were segmented using the automatic artificial intelligence tools followed by manual correction in Circle CVI42 (v5.13.10).
Statistical analysis: We compared RV MBF and MPR among the control, CTEPH pre, and CTEPH post-PTE using ANOVA with Bonferroni correction as the post hoc test. Pearson correlation was used to determine the relationship between RV MPR and pulmonary hemodynamics (i.e., mPAP [mean pulmonary arterial pressure], mRAP [mean right arterial pressure], PVR [pulmonary vascular resistance] in wood unit, CO [cardiac output]), RV functional parameters, and their changes (post-pre). The mean time between MRI and RHC was 61 [22,117] days for pre-PTE and 114 [5,176] days for post-PTE.
Results
Figure 2 showed representative stress-rest MBF maps and the corresponding MPR values from a control patient and one responder and one non-responder to PTE, with corresponding mPAP. Following PTE, CTEPH patient 1 experienced a significant improvement in RV perfusion reserve (post-PTE RV MPR = 2.40 vs pre-PTE RV MPR = 1.25), whereas CTEPH patient 2 did not show the same level of improvement (post-PTE RV MPR = 1.48 vs. pre-PTE RV MPR = 1.48). Nonetheless, the perfusion results were consistent with mPAP obtained through RHC. As summarized in Table 1, RV MPR and stress RV MBF were significantly reduced in CTEPH patients pre-PTE compared to the control cohort. RV MPR was significantly correlated with mPAP (r= -0.75) (Figure 3), RVESV (r = -0.67), and RVEF (r = 0.67) (Figure 4) (p<0.05).Discussion
In this study, we observed that patients with CTEPH had lower RV MPR compared with the control cohort, and that MPR improved following PTE. RV MPR was significantly correlated with mPAP, RVSEV and RVSV. There was non-significant associations between RV MPR and changes in pulmonary hemodynamics and RV functions, owing to the small sample size. To our knowledge, this represents the first study of successful pixel-wised quantification of the RV free wall using MRI for patients with CTEPH and comparison between RV perfusion reserve and invasive pulmonary hemodynamics and RV functions pre and post-PTE.Conclusion
RV perfusion reserve is significantly reduced in CTEPH patients pre-PTE, improves post-PTE, and strongly correlates with invasive pulmonary hemodynamics and RV functions, suggesting that it may serve as an imaging marker for monitoring treatment efficacy. Future studies include a larger study of CTEPH patients undergoing PTE to further explore the findings in this study.Acknowledgements
This work is supported by the National Institutes of Health (R01HL116895, 1R01HL167148‐01A1, R01HL151079, R21EB030806A1), the Radiological Society of North America (EILTC2302) and the American Heart Association (19IPLOI34760317, 949899, 903375).References
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