RESUMEN
In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6 ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10 ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4 mL/min (standard deviation [SD] 20.2 mL/min) versus 59.2 mL/min (SD 17.4 mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3 mL/min (95% CI 11.1-25.6 mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade ≥2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p = 0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage.
Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Everolimus/uso terapéutico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón , Inmunosupresores/uso terapéutico , Enfermedades Vasculares/tratamiento farmacológico , Adolescente , Adulto , Anciano , Aloinjertos , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Cardiopatías/cirugía , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Receptores de Trasplantes , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología , Privación de Tratamiento , Adulto JovenRESUMEN
Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Everolimus/uso terapéutico , Rechazo de Injerto/prevención & control , Cardiopatías/cirugía , Trasplante de Corazón , Receptores de Trasplantes , Enfermedades Vasculares/tratamiento farmacológico , Adulto , Aloinjertos , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Supervivencia de Injerto , Cardiopatías/complicaciones , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Sirolimus/uso terapéutico , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiologíaRESUMEN
In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (36 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 711 weeks and everolimus exposure increased (610 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m2 vs. 61.5 ± 19.6 mL/min/1.73 m2; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 711 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p < 0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
Asunto(s)
Inhibidores de la Calcineurina/administración & dosificación , Trasplante de Corazón , Inmunosupresores/administración & dosificación , Sirolimus/análogos & derivados , Corticoesteroides/administración & dosificación , Adulto , Anciano , Ciclosporina/administración & dosificación , Esquema de Medicación , Everolimus , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Insuficiencia Cardíaca/cirugía , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Sirolimus/administración & dosificación , Serina-Treonina Quinasas TOR/metabolismo , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: Early and long-term survival in patients suffering from cardiogenic shock is poor. Treatment with mechanical assist devices is complicated and expensive but claim to improve survival. We reviewed our experience of venoarterial extracorporeal membrane oxygenation (ECMO) in patients with acute cardiogenic shock. DESIGN: ECMO was used in 52 patients with cardiogenic shock. They were divided into those not operated upon previously (n=19) and those having had cardiac surgery prior to circulatory collapse (n=33). RESULTS: Twenty-six patients were weaned from ECMO. Early mortality for all patients was 48%. Mortality beyond 30 days was 5.8%, with no mortality in the non-cardiotomy group. Long-term survival for patients in the non-cardiotomy group was 63%, as compared to 33% in post-cardiotomy patients (p=0.07). Age over 55 years, female gender or cannulation site did not appear to influence survival. CONCLUSION: Mortality for patients in cardiogenic shock is very high. Treatment with ECMO in patients with refractory cardiogenic shock can be performed with good survival especially in non-surgical patients.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Choque Cardiogénico/terapia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Oxigenación por Membrana Extracorpórea/instrumentación , Oxigenación por Membrana Extracorpórea/mortalidad , Femenino , Corazón Auxiliar , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/terapia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Choque Cardiogénico/etiología , Choque Cardiogénico/mortalidad , Suecia/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to test the hypothesis that angiotensin converting enzyme inhibition or angiotensin II antagonism can counteract cardiac human vascular endothelial growth factor-A165 (phVEGF-A165) induced angiogenesis. METHODS: Mice were given a single intramyocardial injection of phVEGF-A165. Either enalapril or candesartan was given subcutaneously for 10 consecutive days. Hearts were harvested and capillary count was performed by immunohistochemistry. With similar design, groups of mice were sacrificed after 24 h for the determination of tissue expression of phVEGF-A protein, mRNA expression of mouse VEGF-A, and VEGF receptors 1 and 2, after pEGFP-Luc transfection for luciferase expression. RESULTS: Increased myocardial capillary density (P < .02) induced by phVEGF-A165 was counteracted by both enalapril (P < .07) and candesartan (P < .02) and then did not differ from control values. We found that phVEGF-A165 induced myocardial hVEGF-A expression (110 +/- 15 pg/heart, P < .0001). Both enalapril and candesartan decreased (P < .01) expression of hVEGF-A to a level not different from control values. Although phVEGF-A165 upregulated (P < .0001) mVEGFR-2, addition of candesartan downregulated endogenous mVEGF-A (P < .0001) and mVEGFR-2 (P < .0001) below the level in normal myocardium. Enalapril or candesartan did not effect luciferase expression. CONCLUSIONS: Enalapril and candesartan both specifically inhibit phVEGF-A165 induced myocardial angiogenesis in the normal heart. The mechanism of inhibition is a combination of inhibition of cardiac hVEGF-A expression and of decreased endogenous expression of the mVEGF ligand and receptor system.
Asunto(s)
Bencimidazoles/farmacología , Enalapril/farmacología , Terapia Genética/métodos , Neovascularización Fisiológica/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Tetrazoles/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Compuestos de Bifenilo , Capilares/efectos de los fármacos , Capilares/fisiología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiología , Luciferasas/genética , Luciferasas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Statins have cardioprotective roles. We explored the cardiac angiogenic effects of simvastatin in combination with transient overexpression of vascular endothelial growth factor (VEGF). Compared with normal mice, 1-year-old ApoE(-/-) mice fed on a high-fat diet (HFD) had about 30% less myocardial capillary (P < 0.001) and arteriolar (P < 0.03) densities, associated with decreased VEGF (55%), VEGFR-1 (56%) and VEGFR-2 (78%) mRNA expressions and myocardial endothelial nitric oxide synthase (eNOS) production (58%). By contrast, angiopoietin-1 and angiopoietin-2 mRNA expressions were increased (500% P < 0.02, and 400% P < 0.01, respectively) in the ApoE(-/-) hearts. No change was observed in Tie-2 gene expression. Phosphorylation of antiapoptotic Akt was lower and proapoptotic p38 mitogen-activated protein kinase (MAPK) was higher in the ApoE(-/-) mice compared with controls. Intramyocardial VEGF gene transfer increased capillary and arteriolar densities in the ApoE(-/-) mice, and simvastatin treatment further enhanced capillary density (P < 0.03) to a level similar to that of normal mice. Simvastatin did not change the lipid profile but blocked p38 MAPK phosphorylation in the ApoE(-/-) myocardium. Concurrent with these changes, there were increased levels of expression of mVEGF (P < 0.04) and VEGFR-2 (P < 0.03) mRNAs and increased production of eNOS (P < 0.05) in the ApoE(-/-) mice, while no changes were detected in the angiopoietin system. Thus, increased myocardial angiogenesis in the ApoE(-/-) mice following transient overexpression of VEGF is further increased by additional simvastatin treatment. These effects occurred concurrently with simvastatin-induced stimulation of the VEGF system, increased eNOS production and reduction in p38 MAPK phosphorylation.
Asunto(s)
Anticolesterolemiantes/farmacología , Vasos Coronarios/efectos de los fármacos , Técnicas de Transferencia de Gen , Neovascularización Fisiológica/efectos de los fármacos , Simvastatina/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Vasos Coronarios/crecimiento & desarrollo , Humanos , Lípidos/sangre , Ratones , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: It is thought that adult human mesenchymal stem cells do not induce immunoreactivity even to xenografts. We wanted to study whether adult human mesenchymal stem cells survive and engraft in experimentally induced ischemic rat myocardium. METHODS: Bone marrow-derived adult human mesenchymal stem cells (2.5 x 10(6)) were injected into the myocardium of 4 Sprague-Dawley rats. One week after injection, peripheral blood rat lymphocytes were added to adult human mesenchymal stem cells in a mixed lymphocyte reaction. Furthermore, an infarction was created by left anterior descending artery ligation of 8 Sprague-Dawley rats, 4 of which were immunosuppressed with tacrolimus (0.1 mg/kg/d) and 4 RNU athymic rats. One week after left anterior descending artery ligation, 2.5 to 3.5 x 10(6) adult human mesenchymal stem cells were injected around the infarcted area. The adult human mesenchymal stem cells were identified with fluorescence in situ hybridization technique and myocardial antigens by immunohistochemistry. The immune response was studied by hematoxylin and eosin staining and by antibodies directed toward macrophages. RESULTS: Significant rat lymphocyte proliferation was observed when adult human mesenchymal stem cells were added to peripheral blood from Sprague-Dawley rats previously exposed to adult human mesenchymal stem cells. No reactivity was seen in lymphocytes from untreated Sprague-Dawley rats and athymic rats. Adult human mesenchymal stem cells could only be identified in the myocardium of athymic rats. Further, in normal Sprague-Dawley rats, there was a significant myocardial infiltration of round cells, mostly macrophages, in the area of injection of adult human mesenchymal stem cells. In RNU rats, this reaction was less intense. CONCLUSION: Adult human mesenchymal stem cells did not induce xenoreactivity in vitro in previously unexposed immunocompetent Sprague-Dawley rats. However, although mesenchymal stem cells are transplantable across allogeneic barriers, transplant rejection can occur in a xenogenic model. When transplanted into an immunoincompetent host, adult human mesenchymal stem cells showed persistent engraftment.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/inmunología , Infarto del Miocardio/cirugía , Trasplante Heterólogo , Animales , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Inyecciones , Prueba de Cultivo Mixto de Linfocitos , Infarto del Miocardio/patología , Miocardio/patología , Ratas , Ratas Desnudas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: It is thought that a patent foramen ovale (PFO) is the crucial mechanism in patients with suspected paradoxical embolism and cryptogenic stroke. It has been hypothesized that closure of the PFO would prevent further cerebrovascular incidents. We describe our early and late experience with surgical closure of the PFO in patients with paradoxical embolism. PATIENTS AND METHODS: Between May 1994 and December 2001, 33 patients (26 men, 7 women; mean age, 55.2 +/- 8.7 years; range, 37-74) underwent surgical closure of a PFO at our institution. All patients had preoperatively suffered from a stroke and/or a transient ischemic attack, after which echocardiography showed a PFO. Mean follow-up at 99 +/- 30 months (range, 10-111 months) was 100% complete. RESULTS: All patients survived the operative procedure. Early complications occurred in four patients (12%). Actuarial survival at 1, 5 and 8 years was 97 +/- 3%, 97 +/- 5% and 94 +/- 8%, respectively. At long-term follow-up all but two patients were alive. The deaths of these two patients were related to malignancy and ischemic heart disease, respectively. Two patients (6%) had suffered a residual cerebrovascular event after successful surgery. CONCLUSION: Surgical closure of PFO in patients with paradoxical embolism can safely be performed with a low risk of early mortality. Residual thromboembolic events were rare and in those few it occurred it did so with the interatrial septum being closed, indicating that in those patients the PFO was not the mechanism of the thromboembolic event in the first place.
Asunto(s)
Embolia Paradójica/prevención & control , Defectos del Tabique Interatrial/cirugía , Adulto , Anciano , Puente Cardiopulmonar , Embolia Paradójica/etiología , Femenino , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Hipotermia Inducida , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
We report a successful off pump coronary artery bypass case in a patient with a pre-operatively undiagnosed pheochromocytoma. The patient had no signs of ischemia intra- or post-operatively due to aggressive antihypertensive treatment. We would also like to emphasize the importance of using an adequate stabilizing device in order to safely perform anastomoses in a situation like this.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Puente de Arteria Coronaria , Feocromocitoma/complicaciones , Anciano , Humanos , MasculinoRESUMEN
Our institutional experience with 68 pediatric patients undergoing cardiac transplantation was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. The introduction of donor blood insulin cardioplegia was associated with a significant improvement in patient and graft survival. Among 63 ABO-matched transplant procedures, both the patient and graft loss rate were significantly lower (by multivariable analysis) with the use of the donor blood insulin cardioplegia versus conventional cardioplegia, despite significantly longer ischemic times in the former group. Twenty-three (33.8%) patients were deemed at ultra-high risk: eight of 11 patients with cardiomyopathy transplanted following ECMO support survived without major sequelae; three of four additional patients survived early retransplantation. Ten patients underwent intentional ABO-incompatible transplantation under a protocol of plasma exchange on bypass. There were two early deaths because of nonspecific graft failure and respiratory complications with mild vascular rejection, and one late death because of lymphoma. Among seven surviving ABO-incompatible patients followed up to 31 months, there have been no episodes of humoral rejection despite development of antidonor blood group antibodies in A to O, but not B to O, mismatches. The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting salvage of patients conventionally considered at high risk or nontransplantable.
Asunto(s)
Cardiopatías/cirugía , Trasplante de Corazón , Sistema del Grupo Sanguíneo ABO , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Oxigenación por Membrana Extracorpórea , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Cardiopatías/inmunología , Trasplante de Corazón/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Aortic root re-replacement is being performed with increased frequency. Limited information is available regarding the surgical approaches and clinical outcomes of this reoperation. METHODS: Between May 1980 and May 1999, 31 patients (mean age, 45 +/- 15 years) underwent redo composite replacement of the aortic valve and ascending aorta. Indications for reoperation were prosthetic valve endocarditis in 12 patients (39%), failed biological valve in 17 (55%), and false aneurysm in 2 (6%). At reoperation, mechanical valves were implanted in 24 patients and biologic valves in 7. All patients with endocarditis had annular abscess and required reconstruction of the left ventricular outflow tract before implantation of a new valved conduit. Mechanical valves were used in 24 patients, aortic homograft in 4, and bioprosthetic valves in 3. The coronary button technique was used to reimplant the coronary arteries whenever possible. Extension of one or both coronary arteries with a short segment of saphenous vein or a synthetic graft was used in 16 patients (52%). The aortic arch was replaced in 7 patients (23%). RESULTS: There was one operative death (3%) because of rupture of an abdominal aortic aneurysm. The mean follow-up was 47 +/- 46 months and was 100% complete. There were five late deaths (16%), three of which were cardiac related. The actuarial survival was 71% +/- 12% at 5 years. Three patients experienced recurrent prosthetic valve endocarditis 4 months to 8 years after operation. The 8-year freedom from endocarditis for patients operated on for endocarditis was 82% +/- 11% compared with 100% for those operated on for other reasons (p = 0.1). At the last follow-up, 21 of 25 survivors (84%) were in New York Heart Association functional classes I or II, and 4 were in class III. CONCLUSIONS: Redo aortic root replacement can be performed with good early and late results. Patients operated on for prosthetic root endocarditis may have an increased risk of recurrent late endocarditis.
Asunto(s)
Aorta Torácica/cirugía , Válvula Aórtica/cirugía , Implantación de Prótesis Vascular , Implantación de Prótesis de Válvulas Cardíacas , Complicaciones Posoperatorias/cirugía , Adolescente , Adulto , Anciano , Bioprótesis , Causas de Muerte , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Diseño de Prótesis , Falla de Prótesis , Reoperación , Estudios RetrospectivosRESUMEN
OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.
Asunto(s)
Cardiopatías/cirugía , Trasplante de Corazón , Sistema del Grupo Sanguíneo ABO/inmunología , Adolescente , Cateterismo Cardíaco , Niño , Preescolar , Enfermedad Coronaria/etiología , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/prevención & control , Oxigenación por Membrana Extracorpórea , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Cardiopatías/mortalidad , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Lactante , Recién Nacido , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/prevención & control , Masculino , Pronóstico , Circulación Pulmonar/fisiología , Estudios Retrospectivos , Factores de Riesgo , Síndrome de la Vena Cava Superior/etiología , Síndrome de la Vena Cava Superior/mortalidad , Síndrome de la Vena Cava Superior/fisiopatología , Síndrome de la Vena Cava Superior/terapia , Tasa de Supervivencia , Resistencia VascularRESUMEN
BACKGROUND: We reviewed our experience with the Ross procedure to identify the prevalence and predictors of late pulmonary homograft stenosis. METHODS: Between June 1992 and December 1997, 109 consecutive patients (age 34.5 +/- 8.6 years) underwent the Ross procedure, with reconstruction of the right ventricular outflow tract with a cryopreserved pulmonary homograft (22 to 30 mm diameter). There was one early and one late death. Echocardiographic follow-up was available in 105 of 108 patients (97%), with a follow-up of 39 +/- 20 months. Homograft donor and preservation measurements and patient variables were subjected to multivariable analyses to identify independent predictors of late homograft performance. RESULTS: The major physiopathologic finding was homograft stenosis. Peak systolic gradients across the homograft were 20 mm Hg or more in 30 of 105 patients (28.5%) and 40 mm Hg or more in 4 of 105 patients (3.8%). One patient required two re-replacements of her homograft for severe stenosis. Moderate or severe homograft insufficiency was noted in 10 of 105 patients (9.5%). The independent predictors of late pulmonary homograft stenosis were younger donor age (p = 0.03), shorter duration of cryopreservation (p = 0.01), and smaller homograft size (p = 0.06). Beating heart donor status, short homograft ischemic time, and other factors that have been shown to be associated with increased graft viability were associated with graft stenosis but did not reach statistical significance. However, mean gradients across the homograft were significantly related (p = 0.002) to the number of these risk factors in each patient. CONCLUSIONS: Stenosis of the pulmonary homograft can be a significant problem following the Ross procedure, and was predicted by younger donor age and shorter duration of cryopreservation. These factors may be related to increased cellular viability, which might actually predispose to late homograft stenosis in a subgroup of patients.
Asunto(s)
Bioprótesis , Implantación de Prótesis Vascular , Prótesis Vascular , Oclusión de Injerto Vascular/etiología , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Complicaciones Posoperatorias/etiología , Válvula Pulmonar/cirugía , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Pulmonar/anomalías , Trasplante Homólogo , Resultado del TratamientoRESUMEN
In the "Extended" Biocor stentless aortic bioprosthesis, supra- and subvalvular extensions to a bovine pericardium ring carry three porcine leaflets. The extensions cover the "non-coronary" sinus of the prosthesis and allow optional enlargement of the aortic root down towards the mitral valve as well as upwards into the aortotomy. Seventy-one patients with this stentless valve (62 with predominantly aortic stenosis, 28 with concomitant CABG) are being prospectively studied. This paper reports follow-up one year after insertion. The upper and lower pericardial extensions were used in 61 and 11 patients, respectively. The average prosthetic valve size was 23.2 +/- 1.6 mm. Early mortality was 7% (5/71); late mortality (4/66, 5%/patient year) was not valve-related. Symptoms of thromboembolism (new neurological defects) occurred in four patients. There was no valve failure or late endocarditis. One year postoperatively the transvalvular mean pressure difference for all valves was 7.9 (3.1-18.4) mmHg. None of the patients had haemodynamically significant aortic regurgitation at follow-up; nine had trivial regurgitation. The "Extended" Biocor stentless bioprosthesis thus has a favourable haemodynamic profile and can be advantageous in elderly patients with narrow aortic roots, and often with thin and/or calcified aortic walls.
Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Anciano , Anciano de 80 o más Años , Válvula Aórtica , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Femenino , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Falla de Prótesis , Resultado del TratamientoRESUMEN
Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.
Asunto(s)
Estenosis de la Válvula Aórtica/genética , Hipertrofia Ventricular Izquierda/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Anciano , Análisis de Varianza , Estenosis de la Válvula Aórtica/enzimología , Estenosis de la Válvula Aórtica/cirugía , Ecocardiografía Doppler , Femenino , Eliminación de Gen , Frecuencia de los Genes , Genotipo , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/enzimología , Modelos Lineales , Masculino , Estudios ProspectivosRESUMEN
The Toronto-SPV (T-SPV) bioprosthesis has been used for aortic valve replacement (AVR) since July 1991. There is no published data on its mid-term hemodynamic performance. This study compares the hemodynamic data of a consecutive series of patients at 1 and 5 years after AVR. The first 109 consecutive patients who had AVR with a T-SPV have been monitored for a minimum of 5 years and have had annual Doppler echocardiographic studies. There were 80 men and 29 women in the study; mean age was 62 years (range 34 to 80 years). Concomitant coronary artery bypass surgery was done in 35 patients. One operative and nine late deaths occurred. The mean systolic gradient across the T-SPV in all patients was 3.9+/-2.4 mm Hg at 1 year and 4.1+/-3.3 mm Hg at 5 years (P = .27). The mean aortic valve area was 2.2+/-0.6 cm2 at 1 year and 2.3+/-0.7 cm2 at 5 years (P = .43). The mean left ventricular mass index (LVMI) was 104+/-31 g/m2 at 1 year and 97+/-24 g/m2 at 5 years (P = .08). Multivariate linear regression analysis showed that preoperative coronary artery disease (P<.0001) and hypertension (P<.01) were independent predictors of higher LVMI over time. Aortic insufficiency was none/trivial in 94% of patients and mild in 6% at 1 year. At 5 years, aortic insufficiency was none/trivial in 88% of patients, mild in 10%, and moderate in 2%. The aortic leaflets remained thin and pliable in all patients as assessed by echocardiography. Most patients (85%) were in New York Heart Association functional class I. The hemodynamic performance of the T-SPV remained unchanged during the first 5 years after implantation. The LVMI continued to decrease after the first year and tended to normalize in most patients. The aortic valve remained competent, and the leaflets did not change their thickness or show evidence of calcification.
Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica , Femenino , Ventrículos Cardíacos/patología , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Factores de Tiempo , Función Ventricular IzquierdaRESUMEN
BACKGROUND AND AIMS OF THE STUDY: Aortic valve surgery in patients with a narrow aortic root remains a clinical problem. The Extended Biocor Stentless porcine bioprosthesis was specifically designed to allow widening of the aortic annulus in patients with narrow aortic roots. The aim of this prospective study was to evaluate the hemodynamic performance of this prosthesis. METHODS: Serial Doppler echocardiography was used in 50 patients (mean age 77 years, range: 60 to 87 years) during a 15-month follow up after aortic valve replacement. Valve hemodynamics were also assessed in 30 patients at 15 months after surgery, during increased flow rates induced by a supine bicycle exercise test. RESULTS: Of these patients, 60% received valves sized 23 mm or smaller. The mean pressure difference before hospital discharge was 13.8 +/- 5.8 mmHg and this decreased by 40% during the first six months. During the same period there was a significant increase in effective orifice area and a decrease in left ventricular mass. Symptom-limited supine exercise increased cardiac output by 65% while the mean pressure difference increased only slightly (from 8.1 +/- 3.2 to 11.9 +/- 3.6 mmHg). Trivial aortic regurgitation (grade 1+) was detected in 12% of patients at 15 months follow up. All patients who were in NYHA functional class III or IV before surgery were in class I or II after surgery. CONCLUSIONS: We conclude that the Extended Biocor Stentless prosthesis shows low Doppler-derived transvalvular pressure gradients both at rest and during exercise, and also when small-sized valves are employed. Doppler echocardiography, showing low incidence of aortic regurgitation and early regression of left ventricular hypertrophy, demonstrate the beneficial hemodynamic performance of this valve.