Optical Coherence Tomographic Evaluation of Transplant Coronary Artery Vasculopathy With Correlation to Cellular Rejection

Liang, Dong; Maehara, Akiko; Nazif, Tamim; Pollack, Ari; Saito, Shoji; Rabbani, Le Roy E.; Apfelbaum, Mark; Dalton, Kate; Moses, Jeffrey W.; Jorde, Ulrich P.; Xu, Ke; Mintz, Gary S.; Mancini, Donna; Weisz, Giora

doi:10.1161/circinterventions.113.000949

Cited by 44 publications

(19 citation statements)

References 35 publications

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“…In contrast, unique to our study is the fact that we also explored the relationship between rejection data and MPRi and GLS. While several previous studies have suggested a relationship between CAV and historical rejection episodes, these studies have not measured MPRi, and conflicting data exist regarding this relationship [35, 47–49]. With respect to GLS, several previous studies have noted an association between GLS and rejection [15, 18, 50, 51].…”

Section: Discussionmentioning

confidence: 99%

Myocardial perfusion reserve and global longitudinal strain as potential markers of coronary allograft vasculopathy in late-stage orthotopic heart transplantation

Narang

Blair

Patel

et al. 2018

Int J Cardiovasc Imaging

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Coronary allograft vasculopathy (CAV) is a major cause of mortality in late-stage orthotopic heart transplantation (OHT) patients. Recent evidence has shown that myocardial perfusion reserve (MPR) derived from vasodilator cardiovascular magnetic resonance imaging (vCMR) and global longitudinal strain (GLS) from transthoracic echocardiography (TTE) are useful to detect CAV. However, previous studies have not comprehensively addressed whether these parameters are confounded by allograft rejection, myocardial scar/fibrosis, or allograft dysfunction. Our aim was to determine whether changes in late post-OHT MPR and GLS are due to CAV or other confounding factors. Twenty OHT patients (time from transplant to vCMR was 8.1 ± 4.1 years) and 30 controls (10 healthy volunteers and 20 with prior myocardial infarction to provide perspective with regards to the severity of any abnormalities seen in post-OHT patients) underwent vasodilator vCMR from which MPR index (MPRi), left ventricular ejection fraction (LVEF), and burden of late gadolinium enhancement (LGE) were quantified. TTE was used to measure GLS. The presence of CAV was determined from invasive coronary angiograms using thrombolysis in myocardial infarction (TIMI) frame counts and grading severity per guidelines. Previous endomyocardial biopsies were reviewed to assess association with episodes of rejection. We examined the correlations between MPRi and GLS with markers of CAV, allograft function, scar/fibrosis, and rejection. MPRi was abnormal in post-OHT patients compared to both healthy volunteers and MI controls. While there was no relationship between MPRi or GLS and LVEF, episodes of rejection, or LGE burden, both MPRi and GLS were associated with TIMI frame counts and presence and severity of CAV. Additionally, MPRi correlated with GLS (R = 0.68, P = 0.0002). In conclusion, MPRi and GLS are abnormal in late-stage OHT and associated with CAV, but not related to allograft rejection, myocardial scar/fibrosis, or allograft dysfunction. Non-invasive monitoring of MPRi and GLS may be a useful strategy to detect CAV.

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Section: Discussionmentioning

confidence: 99%

Myocardial perfusion reserve and global longitudinal strain as potential markers of coronary allograft vasculopathy in late-stage orthotopic heart transplantation

Narang

Blair

Patel

et al. 2018

Int J Cardiovasc Imaging

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“…Although CAV may develop at any stage after transplantation, events that occur during the first year, most likely arising from immunologically mediated injury to the vascular endothelium, appear to play an important role in CAV pathogenesis (7, 25). Previous studies have demonstrated an association of acute cellular rejection in the early post-transplant period with inflammatory plaque (increased necrotic core and dense calcium contents) and CAV progression late after heart transplantation (3, 7,12). Immunohistochemical studies also suggested that typical CAV lesions display a similar pattern of inflammatory changes when compared to the inflamed myocardium during acute cellular rejection (23,26).…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies of native coronary atherosclerosis, vulnerable plaque does not always accompany severe coronary stenosis, and plaque rupture (or erosion) can occur even in patients with mild-to-moderate disease (29,30). Recent transplant studies also demonstrated the presence of silent plaque rupture and nonocclusive mural thrombi (suggestive of healed plaque rupture and/or erosion) late after transplantation (12,20,31). The present study extended these investigations, indicating that the thrombosis theory might also apply to CAV and that plaque instability could cause cardiac events regardless of significant coronary intimal thickening and/or negative vessel remodeling, suggesting plaque instability as an important independent risk factor for CAV progression.…”

Section: Discussionmentioning

confidence: 99%

“…Patients were monitored for acute cellular rejection using right ventricular endomyocardial biopsies at scheduled intervals post-transplant: weekly during the first month, biweekly until the third month, monthly until the sixth month, and then at 9 and 12 months. Significant acute cellular rejection was defined as the International Society for Heart and Lung Transplantation 2004 revised grade of ≥2R (7,12). Biopsy-proven antibody-mediated rejection (AMR) of grade ≥pAMR2, development of de novo donor-specific antibodies (DSA), and severe rejection with hemodynamic compromise (defined as a decrease in relative left ventricular ejection fraction [LVEF] >25%) during the first year were also evaluated.…”

Section: Methodsmentioning

confidence: 99%

“…Images were analyzed with a validated system (echoPlaque; Indec Systems, Santa Clara, California) at a core laboratory blinded to clinical and angiographic information. Cross-sectional areas were traced at 1 mm intervals throughout the first 50 mm of the left anterior descending artery (LAD) with automated interpolated measurements of the remaining frames (4,7,12). Volumes calculated using Simpson’s method were standardized as volume index (volume/analyzed length, mm 3 /mm).…”

Section: Methodsmentioning

confidence: 99%

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Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation

Okada

Fearon

Luikart

et al. 2016

Journal of the American College of Cardiology

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BACKGROUND While cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events. OBJECTIVES This study’s aim was to characterize the association between ASP and long-term mortality post-heart transplantation. METHODS In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound (IVUS) was performed in the first 50 mm of the left anterior descending artery. ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1 mm intervals. The primary endpoint was all-cause death or retransplantation. RESULTS At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2% ± 9.3% vs. 4.4% ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared to those without. In contrast, maximum intimal thickness did not predict long-term mortality. CONCLUSIONS ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

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Increased coronary lipid accumulation in heart transplant recipients with prior high-grade cellular rejection: novel insights from near-infrared spectroscopy

Zheng

Maehara

Mintz

et al. 2015

Int J Cardiovasc Imaging

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Cardiac allograft vasculopathy is a major cause of morbidity and mortality among patients after heart transplantation. We sought to assess the amount of lipid accumulation in the coronary arteries of transplant patients according to rejection grade. Overall, 39 consecutive heart transplant recipients undergoing annual routine surveillance coronary angiography underwent near-infrared spectroscopy and intravascular ultrasound imaging of 1 coronary artery. Rejection history was graded according to the International Society of Heart and Lung Transplantation (ISHLT) classification as none/mild/moderate-grade rejection (ISHLT 0, 1A/1B, or 2) compared to high-grade rejection (≥3A). Patients with prior history of high-grade rejection had larger plaque burden in the distal coronary segments [45.7 % (25.5-63.7) vs 25.1 % (19.9-37.8), p = 0.02] and a higher maximum lipid core burden index in any 4-mm long segment (maxLCBI(4mm)) [243 (91-400) vs 41 (1-170), p = 0.016] as compared with patients with prior history of none/mild/moderate-grade rejection. By multivariable linear regression analysis, prior history of high-grade rejection was an independent predictor for maxLCBI(4mm). A maxLCBI(4mm) >200 distinguished prior history of high-grade from none/mild/moderate rejection with a sensitivity of 61.5 % and specificity of 84.6 %. The current study demonstrates that the coronary arteries of post heart-transplant patients with a prior history of high-grade cellular rejection have increasing amounts of lipid-rich plaque. MaxLCBI(4mm) >200 might differentiate patients with previous high-grade cellular rejection from heart transplant recipients with none/mild/moderate-grade rejection.

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Optical Coherence Tomographic Evaluation of Transplant Coronary Artery Vasculopathy With Correlation to Cellular Rejection

Cited by 44 publications

References 35 publications

Myocardial perfusion reserve and global longitudinal strain as potential markers of coronary allograft vasculopathy in late-stage orthotopic heart transplantation

Myocardial perfusion reserve and global longitudinal strain as potential markers of coronary allograft vasculopathy in late-stage orthotopic heart transplantation

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation

Increased coronary lipid accumulation in heart transplant recipients with prior high-grade cellular rejection: novel insights from near-infrared spectroscopy

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