Graft Vessel Disease Research Articles

Coronary Angiography and Revascularization Following Coronary Artery Bypass Grafting in British Columbia: Incidence, Predictors and Longer-term Outcomes

BackgroundCoronary artery bypass grafting (CABG) is established treatment for subsets of coronary artery disease (CAD). Observational data have characterised significant progression of native coronary as well as graft vessel disease during longer-term follow-up, potentially reducing the benefit of CABG. We sought to assess longer-term outcomes following CABG by determining rates of repeat coronary angiography, revascularization procedures, and survival. MethodsData for all patients undergoing isolated CABG in British Columbia between 2001 and 2009 inclusive, and with follow-up until the end of 2013, were retrieved from the British Columbia Cardiac Registry. Cox proportional hazard regression and competing risk regression were performed for survival and subsequent cardiac procedures (coronary angiography, percutaneous coronary intervention [PCI] or repeat CABG). ResultsData were available from 17,316 patients with a mean age at index CABG of 65.7 ± 9.8 years. At a median follow-up of 8.5 (range 4.0 to 12.9) years, 3185 patients (18.4%) had died, 3135 (18.1%) underwent repeat coronary angiography with or without PCI or repeat CABG, and 11,557 (66.7%) had survived without additional procedures. Of those who underwent angiography, 1459 patients (46.5%) underwent further revascularization. In multivariate analysis, the strongest predictors of long-term mortality were dialysis dependency and age >75, whereas left internal mammary artery utilization and aspirin therapy were protective. Repeat revascularization predicted survival (adjusted hazard ratio 0.76; 95% confidence interval, 0.63-0.92; P = 0.004), whereas angiography alone did not. ConclusionsFollowing CABG, patients frequently undergo repeat coronary angiography. Although only a minority of patients receive further revascularization, this appears to be associated with longer-term survival.

Depletion of macrophages from Cytomegalovirus (CMV) latently infected donor allografts decreases CMV mediated immunopathology and prevents CMV-accelerated chronic rejection

Abstract Cytomegalovirus (CMV), a ubiquitous β-herpesvirus, is linked to acceleration of solid organ transplant vascular sclerosis (TVS) and chronic rejection (CR). Latent CMV infection increases cardiac-resident macrophages and T cells that may increase inflammation and promote allograft rejection. To investigate the role of cardiac macrophages in CMV mediated TVS/CR, macrophages were depleted from CMV+ donor allografts prior to transplantation using clodronate liposomes (clod) in our rat heart transplant model. Latently rat CMV infected donor F344 rats were treated with clod or PBS or control liposomes 3 days prior to heterotopic cardiac transplant into CMV-naïve Lewis rats and macrophage depletion was validated. Donor hearts were transplanted and monitored daily for rejection. Clod treatment significantly increased graft survival from 61 days post-transplant to 84 days. The severity of graft vessel disease was decreased compared to controls. Clod treatment significant decreased macrophage and T cell infiltration into allograft tissue versus controls. Clod treatment also altered allograft tissue protein and gene expression cytokine/chemokine profiles toward a phenotype that promotes graft survival by reducing the allograft inflammation. Clod treatment did not prevent CMV reactivation since all recipients seroconverted and CMV DNA was detectable in recipient salivary glands. Depletion of donor macrophages prior to transplant represents a novel method to modulate allograft rejection immunity and prevent the negative impact of CMV on allograft recipient survival.

TCT-638 Non-pharmaco, Non-invasive approach in treatment of coronary No-reflow phenomenon

No-reflow is a common complication of percutaneous coronary intervention (PCI) (primary, acute coronary syndrome, stable coronary disease and graft vessel disease) with adverse outcomes. Microvascular obstruction of downstream bed is the culprit. Intracoronary administration of various calcium

Graft Vessel Disease Following Heart Transplantation: A Systematic Review of the Role of Statin Therapy

Graft vessel disease (GVD) is a significant cause of morbidity and mortality in cardiac allograft recipients. Hyperlipidemia is a risk factor for GVD, and the majority of patients will display abnormal lipid profiles in the years following transplant. This systematic review aims to establish the clinical impact of statins in cardiac allograft recipients, critically appraising the literature on this subject. A literature search for randomized studies assessing statin use in cardiac allograft recipients was undertaken. The Cochrane Central Registry of Controlled Trials, MEDLINE, EMBASE, clinicaltrials.gov, and the Transplant Library from the Centre for Evidence in Transplantation were searched. The primary outcome was presence of GVD. Secondary outcomes included graft and patient survival, acute rejection, and adverse events. Meta-analysis was precluded by heterogeneity in outcome reporting and therefore narrative synthesis was undertaken. Seven randomized controlled trials (RCTs) were identified. The majority of RCTs demonstrated some risk of bias, and methods of outcome measurement were variable. Studies reporting incidence or severity of GVD suggest that statins do confer benefit. Survival benefit from statin use is modest. There is a low incidence of adverse events attributable to statins. There was no difference in the overall number of episodes of rejection. Whilst the methodological quality of evidence describing the use of statins in cardiac allograft recipients is limited, the available evidence suggests benefit from their use. This is compatible with the effects of statins in non-transplant patients with cardiovascular disease. Furthermore, the rate of adverse events in the trials is low.

Medication Adherence in Patients Who Undergo Cardiac Transplantation

BackgroundHeart transplant patients are required to take medication for life, both immunosuppressants to prevent rejection and any required for other illnesses. Treatment compliance can be measured quantitatively or qualitatively. Compliance measurement is not easy owing to different factors. The aim of this study was to assess the prevalence of therapeutic compliance in heart transplant patients. MethodsWe undertook a cross-sectional observational descriptive study. The sample comprised patients who received a heart transplant from 2001 to 2011. Of the 203 patients in total, we studied 99. We used the Morisky-Green test as an indirect method and recorded the immunosuppressant blood levels as a direct method. ResultsThe mean age of the patients was 50 ± 12 years, and 84% were male. According to the Morisky-Green test, 33% of the patients were noncompliant, of whom 30% said they rarely forgot to take their medication. Patients took an average of 8 ± 3 drugs per day, but only 85% knew what the drugs were for; 24% of the patients had grade 3A rejection, and 65% had graft vessel disease. ConclusionsTransplanted patients in this study showed a high level of therapeutic adherence that did not differ from other transplant series, either cardiac or other organs, nor from other chronic diseases. The results for defaulters were higher than that expected from these patients. The defaulter results were expected to be lower, given the information that the patients were supposed to have, both before and after the transplantation, and with the strict medical monitoring. Therefore, we have to stress therapeutic compliance, both medical and dietary-hygiene measures, and seek new strategies to improve the results.

Relationship between angiographic graft vessel disease and microvascular reaction after heart transplantation

This study tests the correlation of coronary angiographic findings with the extent of microvascular reaction in right ventricular endomyocardial biopsies (EMBs) in transplanted hearts. In EMBs (n = 209) of 30 heart transplant patients (8 female, 22 male, mean age 48 years) microvascular reaction, i.e. endothelial cell swelling and vascular wall thickening (both grade 0-2), was graded by light microscopy at ×200. Patients' first and last coronary angiography (CA) (mean time after heart transplantation [HTx] 8 and 44 months) were graded according to the Stanford Classification and the presence of diameter irregularities was evaluated semi-quantitatively. We found a correlation of angiographic type B lesions with endothelial cell swelling during the first 5 months and vascular wall thickening during the fifth to fourteenth month after HTx (p <0.05). In patients with diameter irregularities and type B1 lesions in their first CA and type C lesions in their last CA, there was pronounced endothelial cell swelling in the early postoperative period (p <0.05). There was a tendency towards an increased vascular wall thickening in these patients during the later postoperative period. Graft vessel disease affects large and small coronary arteries and capillaries. Small vessel disease is characterized by architectural changes in blood vessel walls. Serial investigations of EMBs for diagnosis of small vessel disease complement the present diagnostic tools.

Cardiac Allograft Vasculopathy: Coronary Computed Tomography and Virtual Histology Assessment

Introduction Cardiac allograft vasculopathy remains the leading cause of late morbidity and mortality in heart transplantation. The main diagnostic methods, coronary angiography or intracoronary ultrasound (when angiography is normal), are invasive. Other study methods, such as coronary computed tomography (CT) and virtual histological analysis, have not been widely assessed in this condition. Objective The objective of this study was to assess the correlation between data obtained from analysis of virtual histology compared with those obtained from the performance of coronary CT in cardiac transplant recipients. Materials and Methods During the same admission we performed coronary angiography and intravascular ultrasound with virtual histological analysis (automatic pull-back in anterior descending artery and one additional vessel if the former was normal) as well as coronary CT. Results The study included 10 patients. Virtual histology was done in segments with intimal thickening >0.5 mm, defining 2 groups of plaque, those with an inflammatory component (necrotic core >30% and calcium) versus those without it defined as the combination of both being <30%. A calcium component of the inflammatory plaque allowed coronary CT detection. Conclusions The detection of inflammatory plaque in graft vessel disease can be based on an initial noninvasive method, such as coronary CT, although confirmation requires further study.

Low‐dose oral sirolimus reduces atherogenesis, vascular inflammation and modulates plaque composition in mice lacking the LDL receptor

Chronic proliferative responses of different vascular cell types have been involved in the pathogenesis of atherosclerosis. However, their functional role remains to be established. Sirolimus reduces neointimal proliferation after balloon angioplasty and chronic graft vessel disease. These studies were undertaken to investigate the effects of this anti-proliferative drug on atherogenesis. Low-density lipoprotein receptor-deficient (LDL r-KO) mice on a cholesterol-rich diet were randomized to receive placebo or sirolimus (0.1; 0.3; or 1 mg.kg(-1)) in their diet for 8 or 16 weeks. In both studies, plasma levels of the drug increased in a dose-dependent fashion, animals gained weight normally and, among groups, plasma lipids levels did not differ significantly. Compared with placebo, plasma levels of interleukin-6, monocyte chemoattractant protein-1, interferon gamma, tumour necrosis factor alpha and CD40, and their mRNA levels in aortic tissue were significantly reduced in sirolimus-treated mice. This effect resulted in a significant and dose-dependent reduction in atherosclerotic lesions, in both the root and aortic tree. Also these lesions contained less monocyte/macrophages and smooth muscle cells, but more collagen. The present results demonstrated that at low doses, sirolimus was an effective and safe anti-atherogenic agent in the LDL r-KO mice. It attenuated the progression of atherosclerosis and modulated the plaque phenotype by reducing the pro-inflammatory vascular responses typical of the disease.

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution

Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)-based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Since 1999, 12 HTx recipients (10 men; 58 +/- 3.6 yr of age; 8.7 +/- 4.2 yr after HTx) with CNI-based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2-4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. After a mean follow-up of 20 +/- 16 months, CreaCl improved significantly: pre-conversion vs. post-conversion: 32.8 +/- 12.2 mg/dL vs. 42.8 +/- 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.

Multislice CT in Graft Vascular Disease. A Pilot Study

Introduction Graft vessel disease (GVD) is one of the main long-term complications in heart transplant (HT) patients. At present, the diagnosis of this complication requires invasive procedures. Multislice CT is an emerging technique that allows visualization of the coronary anatomy, including the vascular lumen and wall thickness. Our objective was to establish the value of 16-detector multislice CT in the detection of GVD, compared with angiography and intravascular ultrasound (IVUS). Patients and methods We studied 32 HT patients, who had a mean follow-up of 2016 days. CT was performed 24 hours prior to angiography, associated with IVUS if the latter proved normal. Comparisons were subsequently made using contingency tables to establish the sensitivity, specificity, and predictive values of the CT. Results Angiography was not performed on two patients, and eight were excluded from CT assessment due to serum creatinine values >1.5 mg/dL. Comparison of the CT findings with the invasive techniques yielded a sensitivity of 50%, a specificity of 81%, a negative predictive value of 81%, a positive predictive value of 50%, and a precision of 72%. Conclusions Our results suggested good performance of the technique in screening for GVD because a high negative predictive value was recorded. We plan to increase the number of patients and use the 64-detector CT system to ensure greater time and spatial resolution.

Sirolimus Experience in Heart Transplantation

Introduction Sirolimus is a potent, nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Recent data support the conversion in late renal failure secondary to calcineurin inhibitors (CNIs), with limited experience in de novo regimens in patients with predictive factors of postoperative renal impairment. Objective We evaluated our experience of sirolimus-based immunosuppression administered to 25 heart transplant recipients. Methods A retrospective analysis of 25 heart transplant recipients who received sirolimus included 17 conversions due to late CNI-related chronic renal dysfunction, six patients with a de novo regimen, and two patients who developed posttransplant pulmonary neoplasms. The conversion from CNI to sirolimus was started with 2 mg, with an average time after transplantation of 78 ± 43 months and a mean baseline serum creatinine level of 2.1 ± 0.45 mg/dL. The mean clinical follow-up was 17 ± 9 months postconversion, and included echocardiography and laboratory studies. In the de novo group successive endomyocardial biopsies were performed during the first semester. Results Serum creatinine fell from 2.1 ± 0.45 mg/dL to 1.8 ± 0.51 mg/dL ( P = .012). Mean sirolimus levels were 15 ± 9 ng/mL (doses 2.2 ± 0.4 mg). This improvement continued until 3 months (creatinine 1.5 ± 0.35 P < .01)/sirolimus levels 11.7 ± 5 ng/mL [1.9 ± 0.7 mg]), with maintenance at 6 months (1.58 ± 0.3 mg/dL/14 ± 4 ng/mL [1.85 ± 0.7 mg]) and 1-year postconversion (1.53 ± 0.39 mg/dL; P = .019/10.7 ± 2.5 ng/mL [1.5 ± 0.7 mg]). De novo, after a mean follow-up of 13 months (range 3 to 35), sirolimus appeared to increase the incidence of a moderate histological grade of rejection without hemodynamic compromise. Side effects were common (63%), including peripheral edema, skin eruptions, and pericardial effusion. Only one patient discontinued treatment, due to intestinal intolerance. Four patients died during follow-up: two because of lung neoplasms and two because of progressive graft vessel disease. Conclusion Sirolimus improved late CNI-related chronic renal dysfunction. Kidney function was preserved using a de novo CNI-free immunosuppressive regimen for recent cardiac transplant recipients.

159: Validation of the prognostic value of a new intravascular ultrasound score for the evaluation of graft vessel disease

159: Validation of the prognostic value of a new intravascular ultrasound score for the evaluation of graft vessel disease

163: Why do some heart transplantation recipients not develop graft vessel disease on the long term?

163: Why do some heart transplantation recipients not develop graft vessel disease on the long term?

Calcineurin inhibitor-free immunosuppression after heart transplantation: can chronic side effects be avoided?

Purpose of review This paper discusses the recent findings on the subject of whether calcineurin inhibitor-free immunosuppressive regimens might be feasible and safe. Randomized trials and longer-term follow-up will help to establish whether such regimens could be used to avoid or reverse the chronic side effects associated with calcineurin inhibitors. Recent findings The introduction of mycophenolate mofetil and sirolimus resulted in several approaches to begin long-term immunosuppression independently of calcineurin inhibitors. In patients with calcineurin inhibitor toxicity, calcineurin inhibitor withdrawal resulted in a reversal of calcineurin inhibitor-induced renal failure in most reports. Conversion to mycophenolate mofetil and steroids was associated with improved renal function, but the incidence of rejections and graft vessel disease increased. In contrast, mycophenolate mofetil combined with sirolimus as conversion therapy improved renal function and was efficacious and safe. Therefore, interest is growing in de-novo calcineurin inhibitor-free regimens to completely avoid calcineurin inhibitor toxicity. Unfortunately, most reports of calcineurin inhibitor-free immunosuppression were retrospective analyses, and only two prospective, but noncomparative, studies exist. Summary First experiences with calcineurin inhibitor-free immunosuppression after heart transplantation are made as a conversion approach and as de-novo therapy. The superiority in safety and efficacy of calcineurin inhibitor-free immunosuppression has to be proven in randomized trials. Longer follow-up will answer the question regarding the prevention of adverse events like renal failure or graft vessel disease and prolongation of patients' survival.

Freedom From Graft Vessel Disease in Heart and Combined Heart- and Kidney-transplanted Patients Treated With Tacrolimus-based Immunosuppression

In end-stage cardiomyopathy where concomitant chronic renal failure is a contraindication for cardiac transplantation (HTx), simultaneous heart and kidney transplantation (HKTx) may be the only feasible therapeutic option. Due to the increased donor shortage, the clinical outcome of combined HKTx patients on tacrolimus-based immunosuppression was assessed and compared with a group of HTx patients. Three hundred forty-nine HTxs, including 13 (4%) combined HKTxs, were performed since 1995. Two hundred twenty-one HTx and all HKTx recipients received tacrolimus-based immunosuppression. Acute rejection episodes (AREs), infections, renal function and clinical outcome were evaluated. Pre-operative renal diagnoses for HKTx patients included cystic nephropathy (n = 4), glomerulonephritis (n = 4), cytostatica-induced nephropathy (n = 1), chronic rejection after renal transplant (n = 1), reflux nephropathy (n = 2) and chronic calcineurin-inhibitor -induced nephropathy after HTx (n = 1). Twelve patients (92%) were on hemodialysis pre-operatively, 1 underwent implantation of a left ventricular assist device (LVAD) before HKTx. After 4.7 +/- 2 years, 92% of HKTx compared with 85% of HTx patients had survived (p = 0.42). Acute cardiac rejection episodes were more frequent in HTx than in HKTx patients (0.04 +/- 0.09 vs 0.02 +/- 0.04 ARE/100 patient-days; p = 0.07). Incidence of infection was comparable (0.3 +/- 0.2 vs 0.5 +/- 0.4 infection/100 patient-days). Freedom from transplant vasculopathy was 100% in the HKTx group compared with 71% in the HTx group after 4 years (p = 0.04). Tacrolimus-based immunosuppression yields promising long-term results in HKTx and HTx. The incidence of transplant vasculopathy seems to be lower after HKTx than after HTx. If these results are secondary to a protective effect of tacrolimus-induced tolerance or of tolerance-associated co-transplantation they will need to be investigated in prospective multicenter trials.

Rapamycin Attenuates Atherosclerotic Plaque Progression in Apolipoprotein E Knockout Mice

Rapamycin has been shown to reduce neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease. This study was designed to test the effect of oral rapamycin on atherosclerotic plaque progression and the possible mechanism involved. Apolipoprotein E (apoE) knockout mice were fed either a diet supplemented with cholesterol or with cholesterol and rapamycin. At 4 and 8 weeks, quantitative analyses of plaque area and macrophage numbers were determined. Plasma cholesterol, triglyceride, and whole-blood rapamycin levels were measured. Rapamycin could be detected in the blood of mice (117+/-7 pg/mL). In mice fed with rapamycin, atherosclerotic lesions covered 22% of the aortic arch as compared with 41% in cholesterol-fed mice. The macrophage count was significantly lower in the rapamycin-fed mice as compared with cholesterol-fed mice. Rapamycin, in a dose-dependent manner, inhibited monocyte chemotaxis elicited by stromal cell-derived factor-1. Lesions in the cholesterol-fed mice had complex atherosclerotic plaque with acellular core, cholesterol clefts, and an abundant collection of monocytes/macrophages. Lesions in the rapamycin-fed mice were mainly composed of monocytes/macrophages. Oral rapamycin is effective in slowing the progression of atherosclerosis. Along with its multitude actions, attenuation of monocyte chemotaxis may be one more way by which rapamycin attenuates plaque progression.

Prevalence of graft vessel disease after paediatric heart transplantation: a single centre study of 54 patients

The study tested the prevalence of graft vessel disease (GVD) in 54 paediatric heart transplant (HTx) patients (32 male, age 0-17 years) who underwent coronary angiographic investigations (N=117). These were evaluated according to the Stanford classification and additional criteria (peripheral obliterations, diameter fluctuations, pathologic tapering) were applied for risk assessment (no GVD/minimal lesions, GVD without Stanford lesions, accelerated GVD). In H&E stainings from right ventricular endomyocardial biopsies (EMB=169) diagnosis of acute cellular rejection (ACR, ISHLT) and microvasculopathy were performed. Mild rejection was found in 43% (N=44) and severe rejection in 7% (N=7) of EMB early (1st year) and mild rejection in 31% (N=32) and severe in 8% (N=9) late (>3 years) after HTx. Microvasculopathy was present in 22% of EMB. Risk assessment of coronary angiographies showed no GVD/minimal disease in 25% (N=29), GVD without Stanford lesions in 12% (N=14) and different grades of accelerated GVD in 74% (N=74) of studies. All patients dying due to cardiac related causes of death (N=6, 3-12 years after HTx) had evidence of GVD. The data show GVD to be an important cause of late cardiac related deaths in this population.

The combination of sirolimus and tacrolimus for primary immunosuppression after heart transplantation-is it worth the effort

Introduction: This combination has hardly been considered for immunosuppression since both compounds compete for the same binding protein. Methods: In a controlled, prospective pilot study 33 patients (pts) were treated with a combination of tacrolimus (tac), sirolimus (sir) and prednisone. Prednisone was completely withdrawn after six months. Mean follow up time was 931 226 days. Results: Survival during follow up was 100%. All but three pts. tolerated the combination well: one pt. was switched to tac/azathioprine, two pts. to sir/mycopehnolate mofetil. Only one pt. revealed an acute rejection episode (ARE) on day 54 after transplantation (0.004ARE/100pt.days). Mean tac/sir trough levels achieved were 8.28 1.74 and 6.27 1.02ng/ml, respectively. The infection incidence (1.5 1.39/pat) was comparable to that of alternative regimes with remarkable less viral infections (0.19 0.4). There were no cases of pneumonitis or wound healing disturbances but 3 cases of pericardial, 1 case of pleural effusion. In 1 patient the trough level of sir had to be decreased because of permanent diarrhea. Non significant adverse events were temporary. Mean cholesterol levels decreased after cessation of steroids, mean creatinine-levels increased slightly. At time of baseline angiography an cav-score of 0.46 1.25 was detected. At one year after transplantation this score was 1.38 3.19 and after two years 1.70 3.50 (p ns). Conclusion: This combination seems to be extremely effective preventing AREs at low trough levels, while infection-incidence proved to be comparable to alternative regimes. Adverse events were non-significant and decreased over time. Therefore, this combination seems to offer an option to decrease target trough levels of each drug, which could not be achieved for each compound in combination with other, less potent agents. Furthermore, due to antiproliferative effects of sir, the combination resulted in a decrease of the incidence of graft vessel disease compared to other immunosuppressive regimes.

Epicardial and microvascular graft vessel disease in children

Graft vessel disease (GVD) is one of the main limiting factors to long-term survival after adult heart transplantation (HTx). The incidence of epicardial and microvascular GVD in paediatric patients was studied. A total of 137 coronary angiographies from 130 paediatric HTx and heart and lung transplant (HLTx) patients (70 male, 60 female, aged 0-18 y) were evaluated according to the Stanford classification and its supplements (minor vessel alterations). In H&E stainings from right ventricular endomyocardial biopsies (EMB = 397), light microscopic diagnosis of acute cellular rejection (ISHLT classification) and vascular reaction (morphology of endothelial cells and vessel walls) was performed. Moderate rejection was present in 32.8% and severe rejection in 13.3% of EMB. Microvascular EC swelling was found in 33.5% and vessel wall thickening in 53.8% of EMB. The results of the coronary angiographic investigations were: Stanford lesions = 61.2%, peripheral obliterations = 52.5%, diameter fluctuations = 86.3%, pathologic tapering = 64.0%, calcifications = 10.8%. Long-term survivors (> or =5 y) showed macrovascular alterations in 78% of cases and microvascular alterations in 67% of cases. The development of micro- and macrovascular GVD is one of the predominant complications in long-term survivors after paediatric HTx and HLTx.

Epicardial and microvascular graft vessel disease in children

Epicardial and microvascular graft vessel disease in children