Paco E Bravo1, Brian A Bergmark2, Tomas Vita1, Viviany R Taqueti1,2, Ankur Gupta1, Sara Seidelmann1, Thomas E Christensen1, Michael T Osborne2,3,4, Nishant R Shah5, Nina Ghosh6, Jon Hainer1, Courtney F Bibbo1, Meagan Harrington1, Fred Costantino2, Mandeep R Mehra2, Sharmila Dorbala1,2, Ron Blankstein1,2, Akshay Desai2, Lynne Stevenson2, Michael M Givertz2, Marcelo F Di Carli1,2. 1. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Cardiovascular Imaging Program, Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, ASB-L1 037-C, 75 Francis Street, Boston, MA 02115, USA. 2. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, ASB-L1 037-C, 75 Francis Street, Boston, MA 02115, USA. 3. Department of Radiology, Cardiac MR/PET/CT Program, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. 4. Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. 5. Division of Cardiovascular Medicine, Department of Medicine, Lifespan Cardiovascular Institute, Brown University Alpert School of Medicine, 830 Chalkstone Avenue, Providence, RI 02908, USA. 6. Ottawa Cardiovascular Centre, 1355 Bank Street, Suite 502, Ottawa, ON K1H 8K7, Canada.
Abstract
Aims: Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection. Methods and results: We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P < 0.001), respectively. Conclusion: Multiparametric cardiac PET evaluation including quantification of MBF provides improved detection and gradation of CAV severity over standard myocardial perfusion assessment and is predictive of major adverse events. Published on behalf of the European Society of Cardiology. All rights reserved.
Aims: Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection. Methods and results: We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P < 0.001), respectively. Conclusion: Multiparametric cardiac PET evaluation including quantification of MBF provides improved detection and gradation of CAV severity over standard myocardial perfusion assessment and is predictive of major adverse events. Published on behalf of the European Society of Cardiology. All rights reserved.
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