Donor-transmitted Atherosclerosis Research Articles

Early optical coherence tomography evaluation of donor-transmitted atherosclerosis and cardiac allograft vasculopathy: insights from a prospective, single-center study

The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality. HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up. A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3±0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p=0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p=0.008) while maximal intimal thickness ≥0.5mm was not. Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.

Paediatric heart transplantation recipients ≥7 years of age receiving donors with pre-existing coronary atherosclerosis showed progressive coronary artery disease.

This study aimed to determine the effect of donor-transmitted atherosclerosis on the late aggravation of cardiac allograft vasculopathy in paediatric heart recipients aged ≥7 years. In total, 48 patients were included and 23 had donor-transmitted atherosclerosis (baseline maximal intimal thickness of >0.5 mm on intravascular ultrasonography). Logistic regression analyses were performed to identify risk factors for donor-transmitted atherosclerosis. Rates of survival free from the late aggravation of cardiac allograft vasculopathy (new or worsening cardiac allograft vasculopathy on following angiograms, starting 1 year after transplantation) in each patient group were estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of the results of intravascular ultrasonography at 1 year after transplantation on the late aggravation of cardiac allograft vasculopathy, correcting for possible covariates including donor-transmitted atherosclerosis, was examined using the Cox proportional hazards model. The mean follow-up duration after transplantation was 5.97 ± 3.58 years. The log-rank test showed that patients with donor-transmitted atherosclerosis had worse survival outcomes than those without (p = 0.008). Per the multivariate model considering the difference of maximal intimal thickness between baseline and 1 year following transplantation (hazard ratio, 22.985; 95% confidence interval, 1.948-271.250; p = 0.013), donor-transmitted atherosclerosis was a significant covariate (hazard ratio, 4.013; 95% confidence interval, 1.047-15.376; p = 0.043). Paediatric heart transplantation recipients with donor-transmitted atherosclerosis aged ≥7 years had worse late cardiac allograft vasculopathy aggravation-free survival outcomes.

Influence of Donor Transmitted and Rapidly Progressive Coronary Vascular Disease on Long-Term Outcomes After Heart Transplantation: A Contemporary Intravascular Ultrasound Analysis

Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation. This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not. In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation.

Donor-Transmitted Atherosclerosis and the Occurrence of Cardiac Antibody-Mediated Rejection Influenced on the Development of Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is still a major cause of mortality in heart transplant (HTx) recipients. Risk stratification for predicting the development of CAV is needed to suppress the development of CAV. Our aim of this study is to clarify the risk factors for the development of CAV. We retrospectively reviewed consecutive 100 HTx recipients who did not have any coronary artery lesions on first coronary angiography at 5 to 12 weeks after transplantation (baseline). Donor-transmitted atherosclerosis (DA) on intravascular ultrasound (IVUS) was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Pathology diagnosis of cardiac antibody-mediated rejection (pAMR) was pathologically diagnosed on the basis of the 2013 ISHLT working formulation. The development of CAV included the any coronary revascularization, acute myocardial infarction and the coronary artery lesions classified ISHLT CAV 1 or 2. DA on IVUS was observed in 62 recipients regardless of no apparent lesions on angiography. pAMR was diagnosed in six recipients within 1year post-HTx. Sixteen recipients had the development of CAV, including five who underwent revascularization, one who had acute myocardial infarction and three who found the moderate lesions classified ISHLT CAV2. DA and the occurrence of pAMR within 1 year post-HTx significantly influenced on the cumulative incidence of development of CAV at a mean follow up period of 6.7±4.6 years after transplantation [Hazard ratio (HR): 5.2, 95% confidence intervals (CI):1.2-23.0, P=0.029 and HR: 7.3, 95% CI:2.0-26.7, P=0.003, respectively]. Multivariable cox proportional hazard model including DA, the occurrence of pAMR and associated variables with the development of CAV showed that DA and the occurrence of pAMR were independently associated with the development of CAV (HR: 5.4, 95%CI:1.2-24.6, P=0.028 and HR: 6.7, 95%CI:1.5-29.1, P=0.012, respectively). DA and the occurrence of pAMR within 1 year post-HTx independently influenced on the development of CAV.

Life expectancy of heart recipients with donor-transmitted coronary atherosclerosis

Introduction . Heart transplantation (HT) is an extreme treatment for chronic congestive heart failure. One of the ways of reducing deficit of donor organs was to expand the criteria for selection of donors in favor of heart retrieval from older donors. This became one of the causes increasing the risk of donor-transmitted coronary atherosclerosis (DTCA). The impact of endovascular DTCA correction on postoperative survival of heart recipients remains poorly studied. Objective : to estimate the life expectancy of heart recipients with donor-transmitted coronary atherosclerosis. Materials and methods . The life expectancy of 518 heart recipients who underwent coronarography during the first week after HT was evaluated. When hemodynamically significant stenosis of the coronary arteries was detected, percutaneous coronary intervention (PCI) was performed as planned. The average age of recipients was 46.92 ± 1 year (10 to 72 years). 90% of them were men. Recipients’ initial UNOS status was distributed as follows: UNOS 1a – 217 people, UNOS 1b – 89 and UNOS 2 – 212. Two groups were formed based on coronary angiography results. Group 1 included patients with DTCA signs, Group 2 was the control group (without DTCA). The first group was divided into 2 subgroups – a subgroup with DTCA signs, but without hemodynamically significant lesions (without PCI), and a subgroup with DTCA, where PCI was performed (PCI). Results . The age of recipients in both groups (DTCA and without DTCA) did not differ – 47.54 ± 1.01 and 46.64 ± 0.64 years, respectively. Donors were older in the DTCA group (50.2 ± 0.7 years) than in the control group (41 ± 0.5 years) (p = 0.0005). Survival in the control group averaged 58.25 ± 1.17 months, and in the DTCA group – 53.16 ± 0.36 months (p = 0.033). The difference in life expectancy of patients who underwent PCI (51.18 ± 2.9 months) and patients of the control group (58.25 ± 1.17 months) was not statistically significant (p = 0.88). In the group where graft showed signs of atherosclerotic changes in the coronary arteries, the cause of donor brain death from cerebrovascular accident was more common than in the control group. Conclusion . The risk of DTCA is associated with the donor’s age and the death of the donor brain from vascular causes. Endovascular correction of atherosclerotic lesions of coronary arteries makes it possible to neutralize the impact of transplant coronary artery stenosis on long-term outcome of HT surgery.

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting in Heart Transplant Recipients With Transplant Coronary Arterial Vasculopathy

BackgroundTransplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. MethodsNinety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. ResultsTCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. ConclusionsCoronary revascularization was feasible and effective for severe TCAV with middle-term follow-up.

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis.

BackgroundThe influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear.MethodsWe performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx.ResultsDonor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002).ConclusionsThis volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.

DONOR-TRANSMITTED CORONARY ATHEROSCLEROSIS

Aim . To estimate opportunities, prospects and safety of using heart transplants from aged donors who are at high risk of coronary atherosclerosis. Materials and methods . Over the period from March 1987 to May 2014 450 heart transplantations (HTx) were performed in V.I.Shumakov Federal Research Center of Transplantology and Artifi cial Organs. During the fi rst month after HTx coronarography was made to 152 (37,8%) recipients in order to exclude/confi rm donor-transmitted coronary atherosclerosis (DTCA) and to identify tactics of treatment. Coronary atherosclerosis was detected among 16 patients (3,6% of total number of HTx), 15 (93,8%) men and 1 (6,2%) women. Mean age of recipients with DTCA at the moment of HTx was 48,3 ± 13,1 years. Results. Hemodynamically relevant coronary atherosclerosis was not detected and percutaneous coronary intervention (PCI) was not made in the group of patients with the mean age of 42,24 ± 8,91 years. Using heart transplants from aged donors is connected with increasing risk of DTCA among the recipients. DTCA-dependent PCI is not connected with coronary mortality. Actuarial survival rate of patients who underwent PCI is comparable with the same one in the total population of HTx recipients and is equal to 87,5% at 5 years and less. Conclusion . Hearts from aged donors (older than 50 years) may be used for HTx with suffi cient level of safety. Due to high level of DTCA using of hearts from such donors is preferable for completing urgent HTx to recipients 1А–В UNOS.

Tissue Characterization of Progressive Cardiac Allograft Vasculopathy in Patients With Everolimus Therapy Compared With Donor-Transmitted Atherosclerosis Assessed Using Serial Intravascular Imaging: A Case Report

Using serial intravascular ultrasound (IVUS), integrated-backscatter IVUS, and optical coherence tomography, we observed rapidly progressive cardiac allograft vasculopathy (CAV) and donor-transmitted plaque in the left anterior descending artery. Late-phase everolimus-resistant CAV had a rapidly progressive course (maximal intimal thickness [MIT] increased by 0.5 mm between years 3 and 4 after cardiac transplantation, from MIT growth <0.5 mm at year 1). Conversely, the donor-transmitted plaque grew slowly (0.1 mm increase during the same period). Tissue characteristics in the 2 segments were also different; CAV had eccentric, noncalcified, and lipid-rich components and was associated with macrophage accumulation, whereas donor-transmitted atherosclerosis presented with typical features of atherosclerosis (ie, fibrocalcific plaque). CAV with late-phase progression involves everolimus resistance and features of vulnerable plaques seen in nontransplantation patients and is independent of donor-transmitted atherosclerosis.

Prevalence of donor-transmitted atherosclerosis—Clinical utility of intracoronary ultrasound early after heart transplantation. A single-center study

IntroductionCoronary allograft vasculopathy (CAV) is one of the main factors limiting long-term survival following orthotopic heart transplantation (HTx). Whether or not and, if so, how donor-transmitted atherosclerosis (DCA) affects the post-transplant course of the allograft recipient is still unclear. Conventional coronary angiography is a moderately accurate technique for DCA detection as it will reveal only the more gross morphological lesions. By contrast, intravascular ultrasound (IVUS) has been shown to be a much more sensitive technique for CAV and DCA detection. In our study we sought to determine the prevalence of DCA in our HTx patient population and identify main risk factors of DCA based on donor characteristics. Patients and methodsWe performed a retrospective analysis of data of 119 patients (92 men, 27 women) undergoing transplantation in our center from August 2006 through September 2012, who had survived their first post-transplant month and had coronary angiography and IVUS. ResultsDCA was present in 39 patients, and not documented in 80 patients. The main risk factors for DCA included donor age, cigarette smoking, and hypertension; the other parameters were not shown to be statistically significant. In-hospital mortality was low in both groups (DCA positive and DCA negative), with one patient dying in either group. One-year mortality rates post-HTx were likewise almost identical in both groups (15.4% and 15% in DCA positive and negative, respectively). ConclusionThe prevalence of DCA in our patients was 32.8%, with major risk factors for DCA including donor age, cigarette smoking, and hypertension. As age seems to be the strongest predictor, coronary angiography should be a routine examination in individuals aged over 40 years; the examination should be considered in younger individuals with a cluster of several of risk factors. The 1-year survival in this selected patient population was identical in both groups, the implication being that the diagnosis of DCA had no effect on 1-year survival post-HTx.

Impact of Donor-Transmitted Atherosclerosis on Early Cardiac Allograft Vasculopathy: New Findings by Three-Dimensional Intravascular Ultrasound Analysis

The influence of donor-transmitted coronary atherosclerosis (DA) on plaque progression during the first year after cardiac transplantation (Tx) is unknown. Serial 3-dimensional intravascular ultrasound (IVUS) studies were performed within 8 weeks (baseline; BL) and at 1 year after Tx in 38 recipients. On the basis of maximum intimal thickness (MIT) at BL, recipients were divided into DA group (DA+; MIT≥0.5 mm, n=23) or non-DA group (DA-; MIT<0.5 mm, n=15). Plaque, lumen, and vessel volume indexes were calculated by volume/measured length (mm/mm) in the left anterior descending artery. Univariate and multivariate regression analyses were attempted to reveal clinical predictors of change in coronary dimensions. During the first year after Tx, plaque volume index increased significantly in DA+ group, but did not change in DA- Group (DA+, 3.0±1.5 to 4.1±1.5 mm/mm, P<0.0001: DA-, 1.2±0.4 to 1.3±0.5 mm/mm, P=0.53). In both groups vessel volume index decreased significantly (DA+, 16.3±3.6 to 14.6±3.3 mm/mm, P=0.003: DA-, 13.5±4.1 to 12.0±3.3 mm/mm, P=0.01), as did lumen volume index (DA+, 13.2±3.1 to 10.5±2.7 mm/mm, P<0.0001: DA-, 12.2±3.7 to 10.7±3.0 mm/mm, P=0.004). Univariate and multivariate regression analyses revealed that DA was one of the strongest predictors for plaque progression. DA was associated with significant plaque progression during the first year after Tx, and in conjunction with negative remodeling, may be an important determinant of cardiac allograft vasculopathy.

In vivo characterization of plaque composition in late Cardiac Allograft Vasculopathy

Purpose: Allograft vasculopathy is the leading cause of late mortality after cardiac transplantation. Late cardiac allograft vasculopathy, as seen at necropsy, manifests as a diffuse obliterative process characterized by concentric intimal proliferation. Investigation of coronary plaque composition in vivo has become possible with the introduction of virtual histology (VH) intravascular ultrasound (IVUS). In this study we evaluated the feasibility of in vivo plaque characterization in late allograft vasculopathy using VH-IVUS. Methods and Materials: 15 patients (median age 61years; 3273years) 8 years (4-14years) after heart transplantation were included into this study. In all patients at least one coronary artery was investigated using VH-IVUS. VH-IVUS data were obtained using a continuous pullback (0.5mm/s) and a commercially available mechanical sector scanner (Eagle Eye GoldTM, Volcano Therapeutics). A region of interest (11-15mm) was selected and analyses were done offline with pcVH-review software (Volcano Therapeutics). Four histological plaque components (fibrous, fibrolipidic, necrotic and calcified) were correlated with a specific spectrum of the radiofrequency signal. Results: Median plaque length was 14mm (11-15mm), vessel segment volume 209mm3 (125-314mm3), and plaque-plus-media-volume 95mm3 (46-156mm3), resulting in a volume stenosis of 44% (34-56%). The remodeling index was 1.01 (0.88-1.21). VH demonstrated that 67% (47-77%) of plaque volumen was composed of fibrous, 10% (5-19%) of fibrolipidic, 14% (8-26%) of necrotic and 7% (2-12%) of calcified tissue. Conclusions: In vivo analysis of plaque composition in cardiac allograft vasculopathy is feasible using VH-IVUS. The high proportion of fibrous tissue identified by VH is well in line with post mortem data. It can be speculated that the addition of VH to standard IVUS will be helpful for the differentiation between early allograft vasculopathy from donor-transmitted atherosclerosis, and for investigating the effects of new therapy on disease progression.

Assessment of Early Atherosclerosis in de novo Heart Transplant Recipients: Analysis with Intravascular Ultrasound-Derived Radiofrequency Analysis

Cardiac allograft vasculopathy (CAV) is the major limitation in survival of patients after heart transplantation. Cardiac allograft vasculopathy is angiographically silent in the early phase after operation. Intravascular ultrasound (IVUS) is a more sensitive method to detect the early stages of CAV and provides information about its development. Recent IVUS studies demonstrated a rapid progression of CAV within the first year after transplantation as a predictor of morbidity and mortality. This study assessed the plaque composition of early atherosclerosis in transplant patients by radiofrequency analysis. Coronary angiography and IVUS with Virtual Histology (VH) software (Real-Time VH, Volcano Corp, Rancho Cordova, CA) were used to assess 18 patients early after heart transplantation (1.71 +/- 0.47 months). The plaque composition was determined by IVUS radiofrequency data analysis. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. The VH-IVUS acquisition was performed with standardized IVUS (EagleEye catheter; 2.9 F/20 MHz; Volcano Corp) and the VH-IVUS console (Volcano Corp). Coronary angiography did not show any wall irregularities. Intravascular ultrasound demonstrated donor-transmitted atherosclerosis in 6 of 18 patients (33.33%). The incidence, amount of plaque burden, and plaque composition was significantly related to donor age. By VH-IVUS analysis, the plaque composition consisted mainly of fibrotic tissue. Donor-transmitted coronary atherosclerosis is present early after heart transplantation and cannot be detected by coronary angiography. VH-IVUS gives detailed information about the plaque distribution and the plaque composition.