Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation

Chris Anthony; Muhammad Imran; Jim Pouliopoulos; Sam Emmanuel; James Iliff; Zhixin Liu; Kirsten Moffat; Min Ru Qiu; Catriona A. McLean; Christian Stehning; Valentina Puntmann; Vass Vassiliou; Tevfik F. Ismail; Ankur Gulati; Sanjay Prasad; Robert M. Graham; Jane McCrohon; Cameron Holloway; Eugene Kotlyar; Kavitha Muthiah; Anne M. Keogh; Christopher S. Hayward; Peter S. MacDonald; Andrew Jabbour

doi:10.1161/CIRCULATIONAHA.121.057006

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation

Chris Anthony, Muhammad Imran, Jim Pouliopoulos, Sam Emmanuel, James Iliff, Zhixin Liu, Kirsten Moffat, Min Ru Qiu, Catriona A. McLean, Christian Stehning, Valentina Puntmann, Vass Vassiliou, Tevfik F. Ismail, Ankur Gulati, Sanjay Prasad, Robert M. Graham, Jane McCrohon, Cameron Holloway, Eugene Kotlyar, Kavitha MuthiahAnne M. Keogh, Christopher S. Hayward, Peter S. MacDonald, Andrew Jabbour^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR-and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR-or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.

Original language	English
Pages (from-to)	1811-1824
Number of pages	14
Journal	Circulation
Volume	145
Issue number	25
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.121.057006
Publication status	Published - 21 Jun 2022

Keywords

heart transplantation
magnetic resonance imaging

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10.1161/CIRCULATIONAHA.121.057006

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Anthony, C., Imran, M., Pouliopoulos, J., Emmanuel, S., Iliff, J., Liu, Z., Moffat, K., Ru Qiu, M., McLean, C. A., Stehning, C., Puntmann, V., Vassiliou, V., Ismail, T. F., Gulati, A., Prasad, S., Graham, R. M., McCrohon, J., Holloway, C., Kotlyar, E., ... Jabbour, A. (2022). Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation. Circulation, 145(25), 1811-1824. https://doi.org/10.1161/CIRCULATIONAHA.121.057006

@article{4f746f873f3442dfbbe83d4a5db20169,

title = "Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation",

abstract = "Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR-and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR-or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257. ",

keywords = "heart transplantation, magnetic resonance imaging",

author = "Chris Anthony and Muhammad Imran and Jim Pouliopoulos and Sam Emmanuel and James Iliff and Zhixin Liu and Kirsten Moffat and {Ru Qiu}, Min and McLean, {Catriona A.} and Christian Stehning and Valentina Puntmann and Vass Vassiliou and Ismail, {Tevfik F.} and Ankur Gulati and Sanjay Prasad and Graham, {Robert M.} and Jane McCrohon and Cameron Holloway and Eugene Kotlyar and Kavitha Muthiah and Keogh, {Anne M.} and Hayward, {Christopher S.} and MacDonald, {Peter S.} and Andrew Jabbour",

note = "Funding Information: Dr Keogh has conducted clinical trial research for Actelion, Pfizer, United Therapeutics, Arena, Acceleron, Bayer, Respira, GlaxoSmithKline, and Gilead. Dr Macdonald has received an institutional research grant from Novartis and has been on the advisory boards of Novartis and AstraZeneca. The other authors report no conflicts. Funding Information: Funding was provided by the National Heart Foundation of Australia, PhD student scholarship (1015420), Australian Department of Education, PhD student scholarship; and St. Vincent{\textquoteright}s Clinic Foundation, Australia, study funds for imaging. Publisher Copyright: {\textcopyright} 2022 American Heart Association, Inc.",

year = "2022",

month = jun,

day = "21",

doi = "10.1161/CIRCULATIONAHA.121.057006",

language = "English",

volume = "145",

pages = "1811--1824",

journal = "Circulation",

issn = "0009-7322",

publisher = "American Heart Association, Inc.",

number = "25",

}

Anthony, C, Imran, M, Pouliopoulos, J, Emmanuel, S, Iliff, J, Liu, Z, Moffat, K, Ru Qiu, M, McLean, CA, Stehning, C, Puntmann, V, Vassiliou, V, Ismail, TF, Gulati, A, Prasad, S, Graham, RM, McCrohon, J, Holloway, C, Kotlyar, E, Muthiah, K, Keogh, AM, Hayward, CS, MacDonald, PS & Jabbour, A 2022, 'Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation', Circulation, vol. 145, no. 25, pp. 1811-1824. https://doi.org/10.1161/CIRCULATIONAHA.121.057006

TY - JOUR

T1 - Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation

AU - Anthony, Chris

AU - Imran, Muhammad

AU - Pouliopoulos, Jim

AU - Emmanuel, Sam

AU - Iliff, James

AU - Liu, Zhixin

AU - Moffat, Kirsten

AU - Ru Qiu, Min

AU - McLean, Catriona A.

AU - Stehning, Christian

AU - Puntmann, Valentina

AU - Vassiliou, Vass

AU - Ismail, Tevfik F.

AU - Gulati, Ankur

AU - Prasad, Sanjay

AU - Graham, Robert M.

AU - McCrohon, Jane

AU - Holloway, Cameron

AU - Kotlyar, Eugene

AU - Muthiah, Kavitha

AU - Keogh, Anne M.

AU - Hayward, Christopher S.

AU - MacDonald, Peter S.

AU - Jabbour, Andrew

N1 - Funding Information: Dr Keogh has conducted clinical trial research for Actelion, Pfizer, United Therapeutics, Arena, Acceleron, Bayer, Respira, GlaxoSmithKline, and Gilead. Dr Macdonald has received an institutional research grant from Novartis and has been on the advisory boards of Novartis and AstraZeneca. The other authors report no conflicts. Funding Information: Funding was provided by the National Heart Foundation of Australia, PhD student scholarship (1015420), Australian Department of Education, PhD student scholarship; and St. Vincent’s Clinic Foundation, Australia, study funds for imaging. Publisher Copyright: © 2022 American Heart Association, Inc.

PY - 2022/6/21

Y1 - 2022/6/21

N2 - Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR-and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR-or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.

AB - Background: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. Methods: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR-and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR-or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Results: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. Conclusions: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. Registration: HREC/13/SVH/66 and HREC/17/SVH/80. Australian New Zealand Clinical Trials Registry: ACTRN12618000672257.

KW - heart transplantation

KW - magnetic resonance imaging

UR - http://www.scopus.com/inward/record.url?scp=85132454908&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.121.057006

DO - 10.1161/CIRCULATIONAHA.121.057006

M3 - Article

C2 - 35621277

AN - SCOPUS:85132454908

SN - 0009-7322

VL - 145

SP - 1811

EP - 1824

JO - Circulation

JF - Circulation

IS - 25

ER -

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation

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