Angeline Leet

Alfred Hospital, Melbourne, Victoria, Australia

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Publications (16)64.29 Total impact

  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S313-S314. DOI:10.1016/j.healun.2014.01.848 · 5.61 Impact Factor
  • Heart, Lung and Circulation 12/2013; 22:S78-S79. DOI:10.1016/j.hlc.2013.05.187 · 1.17 Impact Factor
  • Rochelle M Gellatly · Angeline Leet · Kathryn E Brown
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2013; DOI:10.1016/j.healun.2013.07.015 · 5.61 Impact Factor
  • Nur-Shirin Harun · Angeline Leet · Matthew T Naughton
    06/2013; 10(3):272-273. DOI:10.1513/AnnalsATS.201304-075SF
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    ABSTRACT: The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.
    The Annals of thoracic surgery 11/2010; 90(5):1541-6. DOI:10.1016/j.athoracsur.2010.05.066 · 3.65 Impact Factor
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    ABSTRACT: Cardiac resynchronization therapy (CRT) is advocated in advanced heart failure; however, patient selection remains challenging. We examined the utility of multi-sequential cardiac magnetic resonance imaging (CMR) in predicting outcome after CRT. We performed multi-sequential CMR on 40 subjects with cardiomyopathy and advanced heart failure, despite optimized medical therapy. All patients had been recommended for CRT according to accepted clinical guidelines. Patients were defined by CMR as likely responders if they had significant mechanical dyssynchrony (> or =65 ms delay between septal and posterolateral wall contraction on cine imaging), and no transmural scarring of the anteroseptal or posterolateral wall on delayed contrast-enhanced imaging. Clinical composite score was recorded at baseline and 6 months post-CRT. Long-term follow-up (transplant-free survival) was 497 +/- 55 days post-CRT. A clinical response was achieved in 19/26 (73%) of the CMR-predicted responders and 2/12 (17%) of the CMR-predicted non-responders (P < 0.01, chi(2)). The sensitivity of CMR for prediction of clinical response to CRT was 90%, with a specificity of 59%. Transplant-free survival post-CRT was achieved in 88% of the CMR-predicted responders and 58% of the CMR-predicted non-responders (P < 0.05, Kaplan-Meier survival analysis). Multi-sequential CMR identifies patients with severe cardiomyopathy who will respond to CRT with a favourable long-term prognosis.
    Europace 02/2010; 12(5):708-13. DOI:10.1093/europace/euq047 · 3.05 Impact Factor
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    ABSTRACT: We evaluated cardiac magnetic resonance imaging (CMR) as a non-invasive test for cardiac allograft rejection. We performed CMR on 50 heart-transplant recipients. Acute rejection was confirmed in 11 cases by endomyocardial biopsy (EMB) and presumed in 8 cases with a recent fall in left-ventricular ejection fraction (LVEF) not attributable to coronary allograft vasculopathy. Control patients had both normal LVEF and no significant rejection on EMB. Cardiac magnetic resonance imaging evaluated myocardial function, oedema, and early and late post-Gadolinium-DTPA contrast enhancement. Patients with confirmed rejection demonstrated elevated early relative myocardial contrast enhancement (4.1 +/- 0.3 vs. 2.8 +/- 0.2, P < 0.001) and a trend to higher oedema suggested by higher relative myocardial intensity on T(2)-weighted imaging compared to controls (2.1 +/- 0.1 vs. 1.7 +/- 0.1, P = 0.1). With rejection defined as increased early contrast enhancement or myocardial oedema, the sensitivity and specificity of CMR compared with EMB were 100 and 73%, respectively. Eight patients with presumed rejection also had elevated early myocardial contrast enhancement compared with controls, (8.7 +/- 1.9 vs. 2.8 +/- 0.2, P < 0.05), which reduced following increased immunosuppression (8.7 +/- 1.9 vs. 4.6 +/- 1.2, P < 0.05). In these patients LVEF improved following increased immunosuppression (32 +/- 5 vs. 46 +/- 5%, P < 0.05). Cardiac magnetic resonance imaging is a promising modality for non-invasive detection of cardiac allograft rejection.
    European Journal of Heart Failure 01/2010; 12(1):45-51. DOI:10.1093/eurjhf/hfp174 · 6.58 Impact Factor
  • Heart, Lung and Circulation 12/2009; 18. DOI:10.1016/j.hlc.2009.05.047 · 1.17 Impact Factor
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    ABSTRACT: Cyclosporine in the form of a microemulsion (Neoral) has been the cornerstone of the majority of immunosuppression regimes in thoracic organ transplantation. Cysporin, an alternative form of cyclosporine, is now available. Although bioavailability has been studied in healthy volunteers and stable renal transplant recipients, there are no bioequivalence data currently available for the population of thoracic organ transplant recipients. This randomized, 2-arm, crossover, open-label study compares the pharmacokinetic profiles of two formulations of cyclosporine (Neoral and Cysporin) in stable heart transplant patients. The pharmacokinetics of Neoral and Cysporin were assessed on 2 study days in 16 stable heart transplant recipients already receiving Neoral, who were at least 15 months post-transplant and had not undergone dose adjustments of Neoral for the previous 3 months. Participants were randomized to receive one study drug for at least 2 weeks with crossover to the other arm for a further 2 weeks. Drug levels were measured from blood samples obtained on the study day at the end of each phase at baseline (pre-dose) and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post-dose. The two formulations of cyclosporine were not found to be bioequivalent for C(max). There was less cyclosporine absorbed with Cysporin than with Neoral (ratio 1.31, 90% confidence intervals 1.20 to 1.42) and, although statistically bioequivalent for area under the curve (AUC), a reduction was observed with the new formulation (ratio 1.17, 90% confidence intervals 1.1 to 1.23). The best fit with AUC was observed at 6 hours post-dose for Neoral and 1.5 hours for Cysporin, not the 2 hours post-dose used clinically. This study suggests that Cysporin may not be clinically bioequivalent to Neoral in heart transplant recipients. The clinical implications of this observation require further exploration in a larger patient cohort.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 10/2009; 28(9):894-8. DOI:10.1016/j.healun.2009.05.015 · 5.61 Impact Factor
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    ABSTRACT: Studies in explanted hearts from patients supported with a left ventricular assist device (LVAD) suggest that no or a less pronounced reverse remodeling process occurs in the right ventricle (RV) during LVAD support. The intermediate-term functional changes in RV function in patients with refractory heart failure (HF) supported with a continuous LVAD are not well characterized. Serial transthoracic echocardiograms and simultaneous measurements of biochemical surrogates of disease severity and organ perfusion were obtained in 20 patients (aged 57 +/- 17 years) with refractory HF before and after implantation of a continuous-flow LVAD (VentrAssist, Ventracor Ltd, Chatswood, Australia). After a median (interquartile range) follow-up of 140 days (34-367 days), RV diameter was reduced (36 +/- 7 vs 33 +/- 4 mm; p = 0.04), as was right atrial area (27 +/- 5 vs 24 +/- 6 cm(2); p = .04). There was a trend toward a reduction in tricuspid annulus plane systolic excursion (14 +/- 6 vs 13 +/- 5 mm; p = .05). RV fractional area change (26% +/- 13% vs 27% +/- 10%; p = .53) and global RV dysfunction graded visually using a scale from 0 (absent) to 3 (severe dysfunction) did not change from pre-implant to follow-up (2 [1-2] vs 1.5 [0.5-2]; p = .18). The degree of global RV dysfunction at follow-up was closely related to the degree of RV dysfunction at the pre-implant study (r = 0.69; p = .001). Changes in global RV dysfunction were inversely related to changes in glomerular filtration rate (r = -0.49; p = .03). During continuous-flow LVAD support, pre-existing RV dysfunction does not worsen in the intermediate term.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2009; 28(4):360-6. DOI:10.1016/j.healun.2009.01.007 · 5.61 Impact Factor
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    ABSTRACT: We report the clinical course of a 16-year-old girl in remission from non-Hodgkin's lymphoma who presented in cardiogenic shock due to a severe anthracycline cardiomyopathy. The patient was initially stabilized using central extracorporeal membrane oxygenation support, followed by conversion to a left ventricular assist device. Unexpected evidence of cardiac recovery 9 months after implant enabled device weaning during a 3-month period, culminating in successful device explantation 1 year after implant. The patient survives 18 months after explant in New York Heart Association class I, on conventional heart failure medical management and metabolic therapy.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2009; 28(1):101-3. DOI:10.1016/j.healun.2008.10.002 · 5.61 Impact Factor
  • The Journal of Heart and Lung Transplantation 02/2009; 28(2). DOI:10.1016/j.healun.2008.11.519 · 5.61 Impact Factor
  • Transplantation 12/2008; 17. DOI:10.1016/j.hlc.2008.05.004 · 3.78 Impact Factor
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    ABSTRACT: Improvements in cardiac transplant practice and immunosuppressive treatment have done much to curb the incidence of acute cellular rejection (ACR); however, antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) remain prevalent. Recent studies have shown that allograft rejection is governed by both allogeneic and nonallogeneic factors such as inflammation. Initial studies have suggested that vascular endothelial growth factor (VEGF), a leukocyte mitogen produced by activated endothelial cells and leukocytes, may play a specific role in not only leukocyte trafficking, but also in the augmentation of ACR and development of CAV. We investigated the localization of VEGF protein using immunohistochemistry in a cohort of 76 heart transplant patients during periods of ACR and AMR and assessed the development of CAV. We showed a significant correlation between lymphocytic localization of VEGF protein and severe ACR (P<0.001). Antibody-mediated rejection positive biopsies taken at 12 months posttransplantation showed significantly greater endothelial localization of VEGF than time-matched AMR negative biopsies (P=0.006). Diffuse endothelial expression of VEGF was also associated with a 2.5-fold increase in the risk of developing CAV (P=0.001). These results show that localization of VEGF protein to the vascular endothelium during AMR is significantly increased in patients who develop CAV. This study also highlights the potential pathogenic role of the endothelial cell in late onset AMR and the development of CAV.
    Transplantation 10/2008; 86(7):991-7. DOI:10.1097/TP.0b013e318186d734 · 3.78 Impact Factor
  • Angeline Leet · Andrew Ross · Donald Esmore · David Kaye
    The Journal of Heart and Lung Transplantation 02/2008; 17(2). DOI:10.1016/j.hlc.2008.05.359 · 5.61 Impact Factor
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    ABSTRACT: Investigation into the contribution of the immune system and inflammatory cascade to acute rejection (AR) and cardiac allograft vasculopathy (CAV) has implicated vascular endothelial growth factor (VEGF). The endomyocardial biopsy (EB) has proved invaluable in the diagnosis of AR, and in providing information concerning the biological processes occurring following transplantation. The association between VEGF and AR and the development of CAV was examined in endomyocardial biopsies (EBs) from a cohort of 76 heart transplant recipients. VEGF mRNA levels were quantified through real time RT-PCR in 712 EBs, obtained at routine intervals during post-operative monitoring. VEGF and leukocyte and endothelial markers were assessed in a subset of biopsies through immunohistochemistry. The results of generalised linear modelling, adjusting for covariates, revealed VEGF mRNA expression was 19% greater during severe AR as compared to no rejection (p=0.007). Immunohistochemical results supported these findings. Mean VEGF mRNA levels were not significant predictors for the development of CAV (p=0.554). However the risk of cardiac related death increased 9-fold for a 1 unit increase in mean VEGF expression (p=0.006). Similarly, a single unit increase in mean AR severity equated to a 10-fold increase in the risk of cardiac related death (p<0.005). Our data suggest that increased VEGF expression is strongly associated with severe AR and cardiac related death.
    Transplant Immunology 02/2008; 18(3):264-74. DOI:10.1016/j.trim.2007.07.006 · 1.83 Impact Factor