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1.
Can Prosthet Orthot J ; 6(1): 41454, 2023.
Article in English | MEDLINE | ID: mdl-38873006

ABSTRACT

BACKGROUND: Despite the recent advancements in the design and manufacture of prostheses for individuals with craniofacial irregularity and amputation, these individuals tend to become self-conscious about their appearance. The aim of this study was to investigate the reliability and validity of Persian version of the Derriford Appearance Scale24 (P-DAS24) for a sample of individuals with craniofacial irregularity and limb loss. METHODOLOGY: Reliability of the P-DAS24 was determined by computing internal consistency and test-retest reliability utilizing Cronbach's alpha coefficient and Pearson's correlation coefficient. Discriminant validity was investigated with comparing the total score of the P-DAS24 between disfigured participants and those with no appearance problem. Known-groups validity was evaluated regarding the participants' gender and their level of involvement. FINDINGS: The sample size comprised of 251 individuals with disfigurement and 101 without disfigurement who were deemed normal in appearance. The P-DAS24 showed satisfactory internal consistency (Cronbach's alpha = 0.89) and excellent test-retest reliability (r = 0.96). The total score of the P-DAS24 showed a statistically significant difference between individuals deemed disfigured or normal (P=0.01). The total scores P-DAS24 in individuals with different levels of involvement were significantly different (P<0.001). The scores of the DAS2, DAS18, DAS21, and DAS24 were significantly different between men and women (P<0.01, <0.01, 0.03, and 0.01, respectively). CONCLUSION: The P-DAS24 is a valid and reliable tool that may be utilized in clinical practice and researches to assess the outcomes of prosthetic reconstructions in individuals with disfigurement.

2.
Transplant Proc ; 49(1): 218-220, 2017.
Article in English | MEDLINE | ID: mdl-28104142

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) may be used safely as a bridge to lung transplantation in carefully selected elderly patients. We report the case of a 70-year-old patient bridged on ECMO before transplantation. A brief discussion on improving outcomes for the elderly and patients bridged on ECMO in general is presented.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Lung Transplantation , Preoperative Care/methods , Aged , Humans , Male , Treatment Outcome
3.
QJM ; 104(4): 335-43, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21106504

ABSTRACT

BACKGROUND: Heart transplantation (HTx), the gold standard therapy for advanced heart failure, is limited by donor availability; alternative therapies are now becoming available. AIM: We examined the outcome of HTx with current immunosuppressive and adjunctive therapy. DESIGN AND METHODS: We analysed the outcome of 399 consecutive patients who underwent transplantation at our centre (1995-2007). Prior to HTx 23% (98) required inotropic support, 8.5% (34) an intra-aortic balloon pump and 11% (43) a ventricular assist device. RESULTS: Actuarial patient survival was 86% at 30 days, 79% at 1 year and 62% at 10 years. Survival was similar regardless of the heart failure severity, P=0.22. The cumulative incidence of allograft vasculopathy, Costanzo grade≥2, was 7% at 5 years and 23% by 10 years with an 11% cumulative probability of requiring a percutaneous coronary intervention by 10 years. Allograft function was preserved with a mean±SD left ventricular ejection fraction of 73±7% at 1 year and 74±8% at 10 years. The cumulative incidence of malignancy by 10 years was 27% (skin malignancy 13% and post transplant lymphoproliferative diseases 10%). The cumulative incidence of developing chronic kidney disease (CKD) with an estimated glomerular filtration rate≤45 ml/min/1.73 m2 was 42% at 1 year, 62% at 5 years and 72% at 10 years and of requiring long-term renal replacement therapy was 10.6% at 10 years. CONCLUSION: HTx provided good medium-term survival for patients with advanced heart failure, independent of its severity. The incidence of allograft vasculopathy was lower than reported previously but malignancy and CKD remain cause for concern.


Subject(s)
Heart Failure/surgery , Heart Transplantation/mortality , Adolescent , Aged , Female , Heart Failure/mortality , Heart Transplantation/adverse effects , Heart Transplantation/methods , Humans , Male , Middle Aged , Prognosis , Risk Assessment , Survival Analysis , Tissue and Organ Procurement/methods , Treatment Outcome , United Kingdom/epidemiology , Young Adult
4.
Lancet ; 374(9687): 387-92, 2009 Aug 01.
Article in English | MEDLINE | ID: mdl-19604574

ABSTRACT

BACKGROUND: Cardiac transplantation is a life-saving procedure in infants and children with advanced cardiomyopathy. However, it is greatly limited by shortage of paediatric donors and the complications of long-term immunosuppression, including post-transplant lymphoproliferative disorder (PTLD). We report the management of an infant who had heterotopic cardiac transplantation for advanced cardiomyopathy with secondary pulmonary hypertension who developed seemingly incurable PTLD. METHODS: An 8-month-old girl presented in 1994 with signs of severe heart failure, secondary to dilated cardiomyopathy. At age 11 months, the patient underwent a heterotopic cardiac transplantation. FINDINGS: The patient developed many episodes of PTLD associated with Epstein-Barr virus infection that were resistant to several therapies, including reduction of immunosuppression. Native heart recovery enabled removal of the donor heart 10.5 years after the original operation to allow complete cessation of immunosuppression. Her postoperative course was uncomplicated and the outcome was excellent. 3.5 years after surgery, the patient remains well, in complete remission from her PTLD, and has normal cardiac function. INTERPRETATION: This case shows several issues relating to the use of heterotopic cardiac transplantation in infants and the capacity of the heart to recover. It also provides new insights into the interaction between the immune system with several aspects of modern management of post-transplantation PTLD. FUNDING: None.


Subject(s)
Cardiomyopathy, Dilated/surgery , Epstein-Barr Virus Infections/complications , Heart Transplantation/methods , Immunosuppressive Agents/adverse effects , Lymphoproliferative Disorders/virology , Drug Resistance, Viral , Epstein-Barr Virus Infections/immunology , Female , Heart Transplantation/adverse effects , Heart Transplantation/immunology , Humans , Immunosuppression Therapy/adverse effects , Infant , Lymphoproliferative Disorders/immunology , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Transplantation, Heterotopic , Viral Load
6.
J Heart Lung Transplant ; 25(2): 181-6, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16446218

ABSTRACT

BACKGROUND: The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. METHODS: Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 +/- 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). RESULTS: Mean support time was 14.2 +/- 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. CONCLUSIONS: The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.


Subject(s)
Heart-Assist Devices/standards , Shock, Cardiogenic/therapy , Adolescent , Adult , Anticoagulants/therapeutic use , Child , Female , Heart Ventricles/physiopathology , Heart Ventricles/surgery , Humans , Lactates/blood , Male , Middle Aged , Shock, Cardiogenic/blood , Time Factors , Treatment Outcome
7.
J Heart Lung Transplant ; 23(8): 964-9, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15312826

ABSTRACT

BACKGROUND: Mechanical device failure can be life-threatening and is becoming increasingly important as left ventricular assist devices (LVADs) are being used for longer periods as a bridge to transplantation (period lengthening due to donor shortage) or recovery, or as destination therapy. However, its incidence and clinical management have not been widely studied. METHODS: We investigated the incidence and management of major device failure for a total of 102 Thoratec/TCI HeartMate and Thoratec PVAD devices implanted at our institution since 1995. RESULTS: The cumulative probability of device failure was 6%, 12%, 27% and 64% at 6 months, 1 year, 18 months and 2 years, respectively. Major failure occurred in 8 (7.8%) patients. Four patients presented as emergency cases with vented electric (VE) failure, and 3, with failure due to a seized motor, were supported on the pneumatic driver to explantation, transplantation or device change. Another patient had a ruptured pump diaphragm and was maintained for 12 hours, but died of a Type B aortic dissection. Four patients underwent elective device change, including 2 of a VE pump, 1 with inlet valve regurgitation and fractured power cable at 414 days, and 1 with inlet valve regurgitation at 656 days, all of whom underwent transplantation or explantation. One patient with VE failure was maintained on the pneumatic driver, then underwent Thoratec paracorporeal ventricular assist device (PVAD) implantation and was transplanted. One Thoratec PVAD patient developed LVAD thrombus, underwent pump replacement, and was transplanted. A further patient on the implantable pneumatic (IP) HeartMate developed a pneumoperitoneum due to a leak at the junction of the pneumatic driveline, which was repaired by inserting a new driveline, and underwent heart/kidney transplantation. CONCLUSIONS: Life-threatening mechanical device failure is not uncommon and increases with time, but can be managed successfully in most patients. Improvements in design and manufacture should further enhance outcome with LVADs.


Subject(s)
Equipment Failure/statistics & numerical data , Heart-Assist Devices , Ventricular Dysfunction, Left/therapy , Adult , Female , Humans , Incidence , Male , Middle Aged , Time Factors
8.
Circulation ; 109(19): 2263-5, 2004 May 18.
Article in English | MEDLINE | ID: mdl-15136495

ABSTRACT

BACKGROUND: Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown. METHODS AND RESULTS: We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed approximately 50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca2+ content was increased in the recovery compared with the nonrecovery group. CONCLUSIONS: These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca2+ handling as a key functional determinant in patients with heart failure.


Subject(s)
Calcium Signaling , Calcium/analysis , Heart Failure/therapy , Heart-Assist Devices , Myocytes, Cardiac/chemistry , Sarcoplasmic Reticulum/ultrastructure , Caffeine/pharmacology , Calcium Channels, L-Type/metabolism , Cardiovascular Agents/therapeutic use , Cell Size , Combined Modality Therapy , Heart Failure/drug therapy , Heart Failure/metabolism , Heart Failure/pathology , Heart Failure/surgery , Heart Transplantation , Heart Ventricles/pathology , Humans , Ion Transport/drug effects , Myocytes, Cardiac/pathology , Remission Induction , Sarcoplasmic Reticulum/chemistry , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Left/metabolism , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/therapy
9.
J Heart Lung Transplant ; 22(1): 50-7, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12531413

ABSTRACT

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a leading cause of morbidity and mortality after lung and heart-lung transplantation. Present treatment is directed at the augmentation of pharmacologic immunosuppression. METHODS: This study examines the effect of substituting cyclosporine with tacrolimus on the forced expiratory volume in 1 second (FEV(1)) and on the forced expiratory flow between 25% and 75% of vital capacity (FEF(25%-75%)) in 32 patients who developed BOS. The proportional rates of decline of FEV(1) and FEF(25%-75%) before and after treatment with tacrolimus were calculated. The actuarial survival of responders and non-responders to tacrolimus was compared. Pre-operative and post-operative factors were investigated to determine any difference between the 2 groups. RESULTS: There were significant reductions in the rates of decline of FEV(1) and FEF(25%-75%) when the rates in the 3 months before conversion to tacrolimus were compared with subsequent rates at 0 to 3 months, 3 to 6 months, 6 to 9 months and 9 to 12 months after conversion. The rates of decline of FEV(1) and FEF(25%-75%) in the 3 months before conversion were 0.11 liters/month and 0.13 liters/s per month, respectively. This compares with the rates of decline for FEV(1) and FEF(25%-75%) for the 3 months after conversion to tacrolimus of 0.04 liters/month (p = 0.023) and 0.04 liters/s per month (p = 0.022), respectively. The actuarial survival at 1 year from the time of conversion to tacrolimus for the responder sub-group and the non-responder sub-group were 89.2% and 75%, respectively, and at 4 years after conversion were 61.3% and 56.3%, respectively (p = 0.92). CONCLUSIONS: Tacrolimus rescue therapy is effective at stabilizing lung function in patients with BOS, and this effect is apparent up to 12 months after conversion from cyclosporine.


Subject(s)
Bronchiolitis Obliterans/drug therapy , Cyclosporine/therapeutic use , Heart-Lung Transplantation , Immunosuppressive Agents/therapeutic use , Lung Transplantation , Lung/physiopathology , Tacrolimus/therapeutic use , Bronchiolitis Obliterans/immunology , Bronchiolitis Obliterans/physiopathology , Forced Expiratory Volume , Humans , Spirometry , Time Factors
10.
J Thorac Cardiovasc Surg ; 124(6): 1190-7, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12447186

ABSTRACT

OBJECTIVE: We sought to examine our management and outcome of lung carcinoma occurring after thoracic organ transplantation. METHODS: We performed a retrospective review of cases of primary lung carcinoma diagnosed between 1990 and 2000 in patients who have previously undergone thoracic transplantation at our institution. RESULTS: Seventeen patients were identified (1 lung and 16 heart transplants). Median time from transplantation to diagnosis of lung carcinoma was 89 months (range, 46-138 months). Predominant presentation was as an incidental finding at chest radiography (13/17). All patients had smoked cigarettes before transplantation, with 5 continuing to smoke after transplantation. Histologic types were squamous (n = 11), adenocarcinoma (n = 3), small cell (n = 2), and undifferentiated (n = 1). Revised International Union Against Cancer (UICC) clinical stage at the time of diagnosis was stage I or II in 11 of 17 patients. Of these, 9 underwent surgical resection; 2 patients unfit for surgical intervention had radiotherapy. Surgical procedures were lobectomy (n = 5), wedge excision (n = 3), and no resection (n = 1). Median survival after diagnosis was 12 months for all patients and 24 months if the tumor was resected. Six patients who had surgical resection subsequently died (survival of 2, 9, 21, 21, 36, and 67 months); 2 remain alive after 12 and 54 months, respectively. CONCLUSIONS: When possible, surgical intervention should be undertaken for early stage lung cancer occurring after thoracic transplantation because medium-term survival is achievable. Sublobar excisions and definitive radiotherapy should be considered if comorbidity prevents optimal surgical treatment.


Subject(s)
Heart Transplantation , Lung Neoplasms/etiology , Lung Transplantation , Postoperative Complications/therapy , Female , Humans , Life Tables , Lung Neoplasms/mortality , Lung Neoplasms/therapy , Male , Middle Aged , Postoperative Complications/mortality , Retrospective Studies , Survival Analysis , Time Factors
11.
J Heart Lung Transplant ; 21(8): 867-73, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12163086

ABSTRACT

BACKGROUND: Donor availability is currently the major factor limiting the use of heart transplantation as a treatment for severe heart failure. Heterotopic heart transplantation may address this issue by allowing the use of smaller donor organs, which otherwise may not be used. METHODS: We analyzed the outcome of 42 consecutive, adult heterotopic transplantations performed between 1993 and 1999 at our center and compared them with the 303 consecutive orthotopic transplants performed in adult patients during the same period. METHODS: Univariate analysis showed a relative risk for death of 1.8 at 1 year after transplantation for the heterotopic group compared with the orthotopic transplantation group (p = 0.04). Multiple regression analysis using a proportional hazards model showed that donor-recipient size-mismatch, i.e., donor body surface area < or =75% of recipient body surface area (p = 0.0001), donor age (p = 0.0001), and use of a female donor (p = 0.04) were significant risk factors but heterotopic transplantation per se was not. A Kaplan-Meier survival analysis of heterotopic vs orthotopic transplantation showed that 30-day survival was 76% vs 87%. By 1 year, this was 59% vs 74%. At 3 years, the comparison was 56% vs 69%. Repeating this analysis after sub-dividing the heterotopic group into those size-matched vs size-mismatched, the 1-year survival was 81% vs 45%, respectively (p = 0.02). CONCLUSIONS: Heterotopic transplantation using a size-matched graft resulted in similar survival to that seen after orthotopic transplantation during the same period. Heterotopic transplantation with an undersized graft resulted in significantly decreased survival.


Subject(s)
Heart Transplantation , Transplantation, Heterotopic , Cause of Death , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
12.
Circulation ; 104(12 Suppl 1): I233-40, 2001 Sep 18.
Article in English | MEDLINE | ID: mdl-11568062

ABSTRACT

BACKGROUND: Molecular mechanisms underlying the deterioration of patients undergoing LV assist device (LVAD) implantation remain poorly understood. We studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with decompensating heart failure who required LVAD support and compared them with patients with less severe heart failure undergoing elective heart transplantation. METHODS AND RESULTS: Myocardial and serum samples from 23 patients undergoing LVAD implantation were compared with those from 36 patients undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold; P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4 pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL; P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart failure patients and was not further elevated in the LVAD patients. Levels of procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units; P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05), intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were raised in LVAD patients, but caspase-3 and human nuclease CPAN were not. CONCLUSIONS: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in serum of deteriorating patients who required LVAD support. These occurrences may have therapeutic implications and influence the timing of LVAD insertion.


Subject(s)
Apoptosis , Cytokines/biosynthesis , Heart Failure/physiopathology , Myocardium/metabolism , Ventricular Dysfunction, Left/physiopathology , Adolescent , Adult , Cardiac Output, Low , Cardiac Surgical Procedures , Caspases/metabolism , Cytokines/blood , Cytokines/genetics , Disease Progression , Female , Heart-Assist Devices , Humans , Interleukin-1/biosynthesis , Interleukin-1/genetics , Interleukin-6/biosynthesis , Interleukin-6/blood , Interleukin-6/genetics , Male , Middle Aged , Myocardium/chemistry , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , Ventricular Dysfunction, Left/therapy
14.
Ann Thorac Surg ; 71(5 Suppl): S368-70, 2001 May.
Article in English | MEDLINE | ID: mdl-11388226

ABSTRACT

BACKGROUND: We have previously shown, by means of electron beam tomography, the pattern of calcification of the aortic root wall of homografts and porcine xenografts after aortic root replacement. However, application of similar methods for cusp calcification raises specific problems that have not been addressed before. METHODS: A new method for localizing and quantifying calcification of the aortic valve cusps has been evolved. Intravenous contrast-enhanced electron beam tomography was introduced to visualize the aortic cusps. This technique was applied to quantify cusp calcification in 37 patients after aortic root replacement with a homograft (group H) or a Medtronic Freestyle valve (group F) at set intervals between 6 months and 2 years. A calcification score in Hounsfield units (HU) and a calcified volume score in cubic millimeters were calculated. RESULTS: The aortic leaflets were clearly visualized in all patients. The mean calcium score in the cusps was 28.8+/-64.4 HU in group F and 62.4+/-66.9 HU in group H (p = not significant). The mean calcified volume score was 327.0+/-425.9 mm3 in group F and 642.0+/-443.0 mm3 in group H (p = not significant). CONCLUSIONS: Contrast enhancement electron beam tomography is a useful tool for quantification of calcium in the aortic valve leaflets. Our preliminary results show a tendency toward more calcification in the homografts. This needs to be studied further in a bigger cohort of patients followed up for longer periods.


Subject(s)
Aortic Valve/surgery , Bioprosthesis , Calcinosis/diagnostic imaging , Heart Valve Prosthesis , Heart Valves/transplantation , Postoperative Complications/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Female , Follow-Up Studies , Heart Valves/diagnostic imaging , Humans , Male , Middle Aged , Prosthesis Design , Prosthesis Failure , Reoperation , Transplantation, Homologous
16.
Heart ; 85(2): 202-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11156673

ABSTRACT

OBJECTIVE: To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre. DESIGN: Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death. PATIENTS: 10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997. RESULTS: Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3-116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%. CONCLUSIONS: Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.


Subject(s)
Amyloidosis/surgery , Cardiomyopathies/surgery , Heart Transplantation , Adult , Cause of Death , Disease Progression , Female , Follow-Up Studies , Graft Rejection , Heart Transplantation/mortality , Hemodynamics , Humans , Male , Middle Aged , Postoperative Care/methods , Prognosis , Recurrence , Retrospective Studies , Survival Rate , Treatment Outcome
17.
Transplantation ; 70(10): 1498-506, 2000 Nov 27.
Article in English | MEDLINE | ID: mdl-11118097

ABSTRACT

BACKGROUND: Myocardial dysfunction is common after brain death, but the mechanisms remain unclear. Apoptosis is tightly regulated by enzymes termed the caspases. We have investigated the caspases involved in the terminal part of the apoptotic pathway in dysfunctional (nontransplanted) donor hearts and their relation to inflammatory markers and compared them to hearts with good ventricular function (transplanted donors). METHODS: Thirty-one donor hearts assessed for transplantation were examined. Western blotting was used to measure pro-caspase-9, caspase-3, DFF45, the activated nuclease CPAN and poly (ADP-ribose) polymerase, a DNA repair enzyme inactivated by caspase-3. Caspase-3 activity was also measured. Histologic and immunocytochemical analysis for HLA Class II and Real Time polymerase chain reaction for tumor necrosis factor-alpha and interleukin 6 were performed to detect inflammatory activation. RESULTS: Cleaved caspase-9 was higher (5.53+/-0.6 vs. 3.64+/-0.4 O.D. units, P<0.01) in nontransplanted compared with transplanted donors and there was a trend for higher pro-caspase-9 (5.20+/-1.0 vs. 4.22+/-0.4 O.D. units, P=NS). Levels of pro-caspase-3 were higher in nontransplanted (9.66+/-0.5 vs. 5.15+/-0.5 O.D. units, P<0.00001) donors and cleavage products of caspase-3 were elevated in 14 of 14 nontransplanted and 2 of 17 transplanted donors. Intact DFF-45 (8.94+/-0.36 vs. 6.14+/-0.30 O.D. units, P<0.000005), its spliced product (2.38+/-0.35 vs. 0.4+/-0.21 O.D. units, P=0.0001) and the nuclease caspase-activated nuclease (2.01+/-0.3 vs. 0.66+/-0.16 OD units, P=0.001) were higher in nontransplanted donors. The caspase-3 substrate poly (ADP-ribose) polymerase was higher in nontransplanted (1.16+/-0.13 vs. 0.61+/-0.22 O.D. units, P=0.57) donors. CONCLUSIONS: The caspases are elevated in dysfunctional donor hearts compared with hearts with good ventricular function with a possible link to inflammatory activation supporting the concept that brain death causes inflammatory activation which can lead to apoptosis with a possible important effect on function.


Subject(s)
Apoptosis/physiology , Heart/physiology , Inflammation/physiopathology , Tissue Donors , Adult , Antibodies/metabolism , Apoptosis Regulatory Proteins , Caspase 3 , Caspase 9 , Caspases/metabolism , Female , Heart Transplantation/immunology , Heart Transplantation/pathology , Heart Transplantation/physiology , Histocompatibility Antigens Class II/biosynthesis , Humans , Male , Myocardium/enzymology , Poly(ADP-ribose) Polymerases/immunology , Proteins/immunology , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/genetics
18.
Eur Heart J ; 21(20): 1698-707, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11032697

ABSTRACT

OBJECTIVES: The aim of this study was to assess the influence of valve substitute (homograft vs prosthetic valve) on the long-term survival and late valve-related complication rates following aortic valve replacement in patients with aortic valve disease and congestive heart failure. BACKGROUND: The effect of choice of valve substitute on outcome after aortic valve replacement in patients with pre-operative heart failure is unknown. The superior haemodynamic profile of homografts may be of particular benefit. METHODS: We retrospectively analysed pre-operative, operative and follow-up data on 518 adults in functional classes III and IV, who, over the 25 years 1969-1993, had their initial aortic valve replacement at Harefield hospital. Follow-up conducted during 1996 to April 1997 and totalling 4439 patient-years was 96.1% complete. Using multivariate analysis, independent risk factors for different complications and mortality were defined. RESULTS: Overall 5-, 10- and 20-year survival was 80+/-2%, 62+/-2% and 30+/-3%, respectively, with no significant difference between valve types. However, homografts (n=381) independently reduced the rate of serious complications and cardiac death, whereas mechanical valves were an independent adverse risk factor for late mortality. The rates of anticoagulant-related bleeding and thromboembolism were increased by mechanical valves, whereas primary tissue failure was the main complication of homografts. CONCLUSIONS: Long-term outcome of homograft aortic valve replacement in patients with congestive heart failure is acceptable, with a reduced rate of serious complications and cardiac death. Further improvements would be expected if the rate of primary tissue failure could be reduced.


Subject(s)
Aortic Valve/surgery , Aortic Valve/transplantation , Heart Failure/surgery , Heart Valve Prosthesis Implantation , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis/standards , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, Homologous/standards
19.
Circulation ; 102(3): 326-31, 2000 Jul 18.
Article in English | MEDLINE | ID: mdl-10899097

ABSTRACT

BACKGROUND-Myocardial failure is an important problem after heart transplantation. Right ventricular (RV) failure is most common, although its mechanisms remain poorly understood. Inflammatory cytokines play an important role in heart failure. We studied the expression of tumor necrosis factor (TNF)-alpha and other cytokines in donor myocardium and their relationship to the subsequent development of RV failure early after transplantation. METHODS AND RESULTS-Clinical details were obtained, and ventricular function was assessed by transesophageal echocardiography in 26 donors before heart retrieval. A donor RV biopsy was obtained immediately before transplantation, and each recipient was followed for the development of RV failure. Reverse transcriptase-polymerase chain reaction was performed to detect TNF-alpha, interleukin-2, interferon-gamma, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-alpha, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-alpha (P<0.005). As a predictor of RV failure, TNF-alpha mRNA had a sensitivity of 87.5%, a specificity of 83.3%, a positive predictive value of 70%, and a negative predictive value of 93.7%. Western blotting demonstrated more TNF-alpha protein in the myocardium of donor hearts that developed RV failure (658+/-60 versus 470+/-57 optical density units, P<0.05). Immunocytochemistry localized TNF-alpha expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction detected interferon-gamma in 2 (7.7%), interleukin-2 in 1 (3.8%), and inducible nitric oxide synthase mRNA in 1 (3.8%) of the 26 donor hearts, none of which developed RV failure. CONCLUSIONS-TNF-alpha expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.


Subject(s)
Cardiac Output, Low/etiology , Heart Transplantation , Myocardium/metabolism , Postoperative Complications , Tissue Donors , Tumor Necrosis Factor-alpha/metabolism , Ventricular Dysfunction, Right/etiology , Adolescent , Adult , Blotting, Western , Cytokines/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , RNA, Messenger/metabolism , Treatment Outcome , Tumor Necrosis Factor-alpha/genetics
20.
J Heart Valve Dis ; 9(1): 97-103, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10678381

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: Unstented aortic valve substitutes offer many of the theoretical advantages of homografts such as superior hemodynamic performance and enhanced durability, particularly when inserted as a root. Many of these depend on the maintained flexibility of the valve components. Calcification of the aortic wall may adversely affect these phenomena. Electron beam computed tomography has been used to evaluate aortic wall calcification in patients undergoing aortic root replacement in a prospective randomized trial designed to compare the Medtronic Freestyle valve with the homograft valve replacement. METHODS: Patients were followed with electron beam computed tomography scans of the aortic root at six-monthly intervals after surgery. A calcification score (Hounsfield units) and a calcified volume score (mm3) were obtained from each scan using a new modified technique. Results were related to hemodynamic data from echocardiography. The prevalence of calcification was also related to the homograft donor age. RESULTS: Seventy-six patients (age range: 40-79 years) were randomized to root replacement with either homograft (n = 31) or Freestyle (n = 45) valves. Fifty-three scans of the aortic root were performed postoperatively in 37 patients. No statistical difference between the two groups was found at six and 12 months after surgery. However, after 18 months the calcified volume score was 5903.8+/-2356.8 mm3 in the homograft versus 2725.6+/-1500.5 mm3 in the Freestyle group (p = 0.017). There was a correlation between calcification score, calcified volume score and left ventricular mass (r = 0.323, p = 0.093 and r = 0.350, p = 0.068, respectively) on the one hand, and calcification score, calcified volume score and valve size on the other hand (r = 0.178, p = 0.466 and r = 0.068, p = 0.780, respectively). CONCLUSIONS: Electron beam computed tomography provides a powerful tool for the detection of calcium in the aortic wall of valve grafts. There is a low rate of calcification during the first 18 months in the Medtronic Freestyle valve, and this appears to be lower than that observed in homografts. Longer-term follow up of the aortic root in these patients is required. This is an ongoing study.


Subject(s)
Aortic Valve/surgery , Calcinosis/etiology , Heart Valve Prosthesis , Postoperative Complications , Adult , Aged , Calcinosis/pathology , Female , Humans , Male , Middle Aged , Postoperative Complications/pathology , Prospective Studies , Transplantation, Homologous
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