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2.
J Heart Lung Transplant ; 30(5): 552-7, 2011 May.
Article in English | MEDLINE | ID: mdl-21212001

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the change in renal function and its determinants after replacement of calcineurin inhibitors with a proliferation signal inhibitor (sirolimus or everolimus) in long-term heart transplant recipients. METHODS: We studied 49 consecutive patients in whom a switch to a proliferation signal inhibitor was carried out 9 ± 4 years after transplantation. Evolutive glomerular filtration rate was assessed at a mean of 28 months after conversion by the simplified MDRD equation. RESULTS: Pre-conversion glomerular filtration rate (40 ± 22 ml/min/1.73 m(2)) remained stable at 1 year after conversion (41 ± 22 ml/min/1.73 m(2)), but decreased significantly by the end of follow-up (35 ± 22 ml/min/1.73 m(2); p = 0.008 and p = 0.002 vs pre-conversion and 1-year values, respectively). In a multivariate model, including age, time from transplantation to conversion, pre-conversion glomerular filtration rate, presence of diabetes and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy, the rate of decline in renal function was related only to the presence of diabetes (p = 0.017) and inversely related to the use of ACEI/ARB therapy (p = 0.003). There were no significant differences with respect to age, time between transplantation and replacement and baseline glomerular filtration rate. CONCLUSION: In long-term heart transplant recipients, late substitution of a calcineurin inhibitor for a proliferation signal inhibitor does not preclude a decrease in renal function in the long-term setting. We identified the presence of diabetes as the main clinical predictor of renal function deterioration. In contrast, we found that the use of ACEI/ARB therapy could exert a protective effect.


Subject(s)
Heart Transplantation/immunology , Immunosuppressive Agents/pharmacology , Kidney/drug effects , Kidney/physiology , Sirolimus/analogs & derivatives , Sirolimus/pharmacology , Adult , Aged , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Calcineurin Inhibitors , Everolimus , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Humans , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Retrospective Studies
3.
J Heart Lung Transplant ; 28(2): 156-62, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19201341

ABSTRACT

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main cause of graft loss and death in heart transplant (HTx) recipients surviving >1 year. There is a dual etiology for coronary disease in HTx: classic atherosclerosis and an immunologically mediated disease. Intravascular ultrasound (IVUS) is highly sensitive for CAV detection; however, gray-scale IVUS is of limited value for identification of specific plaque components. We sought to characterize graft coronary artery disease by means of IVUS-virtual histology (IVUS-VH) at different time-points of follow-up and to correlate plaque composition with clinical factors. METHODS: In our study we included 67 patients, who were 7.6 +/- 5.7 years post-HTx. IVUS gray-scale evaluation was performed on all patients. IVUS-VH analysis was done in those patients showing intimal thickening >0.5 mm at the three more significant lesions (three cross-sections for each) of the left anterior descending artery. RESULTS: IVUS-VH analysis was obtained done on 58 patients (86.5%). We found a significant correlation between time of HTx and IVUS gray-scale parameters (plaque area and plaque burden), with both increasing over time. We also found a significant correlation between time and IVUS-VH-derived plaque components, necrotic core and calcium, which increased with time, and fibrous and fibrofatty components, both decreased at follow-up. IVUS-VH results were also related to donor age and cardiovascular risk factors. CONCLUSIONS: We observed a time-related change in IVUS-VH-derived plaque composition. Necrotic core and calcium, typical atheromatous components, become more prevalent with time after HTx, especially when influenced by cardiovascular risk factors. The presence of a necrotic core in the early stages was linked to older donor age.


Subject(s)
Cardiovascular Diseases/diagnostic imaging , Echocardiography/methods , Heart Transplantation/pathology , User-Computer Interface , Aged , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/pathology , Cardiovascular Diseases/pathology , Coronary Angiography , Female , Follow-Up Studies , Heart Diseases/classification , Heart Diseases/complications , Heart Diseases/surgery , Heart Transplantation/adverse effects , Humans , Male , Middle Aged , Regression Analysis , Time Factors , Tissue Donors/statistics & numerical data
4.
J Heart Lung Transplant ; 27(7): 797-800, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18582812

ABSTRACT

Pulmonary toxicity (PT) is emerging as a frequent and serious complication of sirolimus, a proliferation signal inhibitor (PSI) used in solid-organ transplantation. Everolimus is a more recently developed PSI with molecular structure very similar to that of sirolimus. Surprisingly, although experience with everolimus is increasing and becoming substantial, there remains very little information about everolimus-related PT. Herein we report 2 heart transplant recipients who developed a non-infectious pulmonary syndrome after everolimus treatment was started. Transbronchial pulmonary biopsy specimens showed typical interstitial pneumonitis, and everolimus discontinuation resulted in rapid clinical and radiological improvement. Although PT seems to be more common after sirolimus exposure, everolimus is by no means spared from this potentially lethal complication and should always be suspected in the relevant clinical setting.


Subject(s)
Heart Transplantation , Immunosuppressive Agents/adverse effects , Lung Diseases, Interstitial/chemically induced , Lung/pathology , Sirolimus/analogs & derivatives , Aged , Biopsy , Everolimus , Female , Humans , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Sirolimus/adverse effects , Treatment Outcome
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