Layered Fibrotic Plaques Are the Predominant Component in Cardiac Allograft Vasculopathy: Systematic Findings and Risk Stratification by OCT.
The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity.



Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation.



Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention.



A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV (<70% stenosis), n = 40; and severe CAV (≥70% stenosis), n = 21. Layered fibrotic plaque (LFP) was the most prevalent plaque component, and the extent increased with angiographic CAV severity (p < 0.01). During follow-up, 22 of 172 vessels (13%) experienced NFCP. Median follow-up was 633 days (interquartile range: 432 to 808 days). The extent of LFP (hazard ratio: 5.0; 95% confidence interval: 2.1 to 12.4; p < 0.0001) and the extent of bright spots (hazard ratio: 6.2; 95% confidence interval: 2.4 to 15.8, p < 0.001) were strong predictors of NFCP. By combining LFP and bright spots, a strong NFCP predictive model was obtained (hazard ratio: 8.9; 95% confidence interval: 2.6 to 29.9; p < 0.0001).



OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764).
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark. Electronic address: torclemm@rm.dk.
Tor Skibsted
TS
Clemmensen
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Niels Ramsing
NR
Holm
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Hans
H
Eiskjær
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Brian Bridal
BB
Løgstrup
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Evald Høj
EH
Christiansen
Division of Image Processing, Leiden University Medical Centre, Leiden, the Netherlands.
Jouke
J
Dijkstra
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Trine Ørhøj
TØ
Barkholt
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Christian Juhl
CJ
Terkelsen
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Michael
M
Maeng
Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
Steen Hvitfeldt
SH
Poulsen
D000328:Adult; D000368:Aged; D064591:Allografts; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D023921:Coronary Stenosis / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome
cardiac allograft vasculopathy; heart transplantation; intravascular imaging; optical coherence tomography; time-to-event analysis