Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation

Keerthi T Gondi; Yoav Hammer; Matheos Yosef; Jessica R Golbus; Chaitanya Madamanchi; Keith D Aaronson; Venkatesh L Murthy; Matthew C Konerman

doi:10.1016/j.cardfail.2023.09.013

Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation

J Card Fail. 2023 Oct 27:S1071-9164(23)00377-9. doi: 10.1016/j.cardfail.2023.09.013. Online ahead of print.

Authors

Keerthi T Gondi¹, Yoav Hammer², Matheos Yosef³, Jessica R Golbus², Chaitanya Madamanchi², Keith D Aaronson², Venkatesh L Murthy², Matthew C Konerman²

Affiliations

¹ Department of Internal Medicine, University of Michigan, Ann Arbor, MI. Electronic address: keerthig@med.umich.edu.
² Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI.
³ Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI.

PMID: 37890655
DOI: 10.1016/j.cardfail.2023.09.013

Abstract

Background: Positron emission tomography (PET) myocardial flow reserve (MFR) is a noninvasive method of detecting cardiac allograft vasculopathy in recipients of heart transplants (HTs). There are limited data on longitudinal change and predictors of MFR following HT.

Methods: We conducted a retrospective analysis of HT recipients undergoing PET myocardial perfusion imaging at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors and the prognostic value of MFR after HT.

Results: Of HT recipients, 183 underwent 658 PET studies. The average MFR was 2.34 ± 0.70. MFR initially increased during the first 3 years following HT (+ 0.12 per year; P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P < 0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mammalian target of rapamycin (mTOR) inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (P < 0.001), hypertension (P < 0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4; P < 0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9; P < 0.001) were associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization.

Conclusion: MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk-factor modification and treatment with higher-intensity statin therapy and mechanistic target of rapamycin inhibitors are associated with a higher MFR.

Keywords: Heart transplantation; allograft rejection; cardiac allograft vasculopathy; myocardial flow reserve; positron emission tomography; statin.