Cellular rejection, vasculitis, quilty effect and eosinophilia predicting adverse outcomes and survivorship in heart transplant patients

BACKGROUND: Adverse outcomes affect survival rates in heart transplant (HT) patients. This study aims to evaluate the potential of endomyocardial biopsies (EMB) in predicting adverse outcomes and survivorship in this population. METHODS: We analyzed 952 EMB samples from 107 HT patients (2002-2009) receiving standard cyclosporine, mycophenolate, and prednisone doses. EMBs were assessed for cell rejection, vasculitis, Quilty effect, and eosinophilia patterns. Cell rejection was numerically scored (0R = 0, 1R = 1, 2R = 2, 3R = 3). Other patterns scored 1 for presence, 0 for absence. Scores for each pattern group were averaged per EMB. Biopsies were grouped into predictive (adverse outcomes) and non-predictive (no adverse outcomes). Adverse outcomes were acute rejection (AR) or patient death. Statistical analysis included t-tests (continuous variables), chi-square (categorical variables), and logistic regression (p < 0.05). EMB scores correlated with patient survivorship, analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Of 952 EMBs, 720 were non-predictive, 232 predictive (Fig. 1a). Cell rejection was a significant predictor of AR and mortality (Fig. 1b). Only cell rejection was considered for survivorship, with results in quartiles: Q1 (0-0.43), Q2 (0.44-0.83), Q3 (0.84-1.25), and Q4 (>1.25) (Fig. 1c). CONCLUSION: Among the histological patterns studied, cell rejection can be considered an indicator of adverse outcomes and survivorship rates in HT patients.

Donor hypernatremia and smoking addiction contribute to primary graft failure in heart transplantation

INTRODUCTION: Primary graft failure (PGF) is an important contributor to early mortality, accounting for 41% of deaths within the first 30 days after heart transplantation (HT). Donor hypernatremia has been associated with PGF development. However, controversial data exist regarding the impact of sodium deregulation in patient survival after HT. This study aimed to assess the influence of donor hypernatremia on PGF development and to determine the serum sodium level threshold to assist in decision-making for organ procurement. METHODS: The medical record from 200 HT patients and organ donors were retrospectively assessed and categorized by PGF occurrence. Donor sodium leve were compared and cut-off points obtained by receiver operating characteristic (ROC) curve. A multiple logistic regression model was applied to assess the effects of factors and covariates that influence PGF development. RESULTS: Sodium levels of donors were significantly higher in recipients who developed PGF than those who did not develop PGF (162 vs. 153 mmol/L, p = 0.001). The sodium cut-off value determined by the ROC curve was 159 mmol/L. The group who received organs from donors with a serum sodium concentration >/=159 mmol/L had a higher incidence of PGF (63.3% vs 32.4%, p < 0.001). Furthermore, donor sodium levels >/=159 mmol/L increased the likelihood of recipients developing PGF by 3.4 times. It is also observed that the incidence of donor smoking addiction was significantly higher in the PGF group (28.6% vs. 11.5%, p = 0.004) and donor smoking addiction increased the risk of developing PGF by 2.8 times. CONCLUSION: Smoking addiction and the application of suboptimal organs from donors with hypernatremia contribute to primary graft failure in heart transplantation. (AU)

Donor hypernatremia and smoking addiction contribute to primary graft failure in heart transplantation.

INTRODUCTION: Primary graft failure (PGF) is an important contributor to early mortality, accounting for 41% of deaths within the first 30 days after heart transplantation (HT). Donor hypernatremia has been associated with PGF development. However, controversial data exist regarding the impact of sodium deregulation in patient survival after HT. This study aimed to assess the influence of donor hypernatremia on PGF development and to determine the serum sodium level threshold to assist in decision-making for organ procurement. METHODS: The medical record from 200 HT patients and organ donors were retrospectively assessed and categorized by PGF occurrence. Donor sodium levels were compared and cut-off points obtained by receiver operating characteristic (ROC) curve. A multiple logistic regression model was applied to assess the effects of factors and covariates that influence PGF development. RESULTS: Sodium levels of donors were significantly higher in recipients who developed PGF than those who did not develop PGF (162 vs. 153 mmol/L, P = .001). The sodium cut-off value determined by the ROC curve was 159 mmol/L. The group who received organs from donors with a serum sodium concentration ≥159 mmol/L had a higher incidence of PGF (63.3% vs 32.4%, P < .001). Furthermore, donor sodium levels ≥159 mmol/L increased the likelihood of recipients developing PGF by 3.4 times. It is also observed that the incidence of donor smoking addiction was significantly higher in the PGF group (28.6% vs. 11.5%, P = .004) and donor smoking addiction increased the risk of developing PGF by 2.8 times. CONCLUSION: Smoking addiction and the application of suboptimal organs from donors with hypernatremia contribute to primary graft failure in heart transplantation.

Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long -term heart transplantation

INTRODUCTION: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently verify the way in which it affects the outcome of the allograft. METHODS: In this retrospective study, 300 archives paraffin embedded endomyocardial biopsies from 63 heart allograft recipients were assessed. Cellular rejection and vasculitis were diagnosed through histological analysis, and antibody mediated rejection was performed with immunohistochemical C4d staining. The transcripts of ICAM, VCAM, VEGF, CCL2, IFNG, TGFB, TNF, ADIPOR1, and ADIPOR2 genes were examined through quantitative real -time polymerase chain reaction using B2M for normalization. RESULTS: We observed a higher prevalence of severe vasculitis in the early period of post transplant, and recovery was observed to take place around one year post the transplant. Additionally, vasculitis was found to be directly associated with acute cellular rejection and antibody -mediated rejection. The intense C4d capillary positivity predicts higher long -term cardiovascular disease mortality. In comparison to the vasculitis free group, the group with severe vasculitis displayed reduced left ventricular ejection fraction, and an up -regulation of VCAM and IFNG associated to the down -regulation of VEGF, ADIPOR1, and ADIPOR2. CONCLUSION: The vasculitis associated with the presence of C4d and the change of intragraft gene expression profile may contribute to poor allograft outcomes.

Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long-term heart transplantation.

INTRODUCTION: Vasculitis entails heterogeneous origins; it starts with an inflammatory process that leads to small vessels' necrosis, hemorrhage, and ischemic lesion, and may further result in occlusion of the vascular lumen. Vasculitis' contribution to allograft rejection is still unclear. This study aims to investigate the incidence of vasculitis in the early stages of heart transplantation as well as to assess the intragraft genes' expression associated with vascular function and subsequently to verify the way in which it affects the outcome of the allograft. METHODS: In this retrospective study, 300 archive paraffin-embedded endomyocardial biopsies from 63 heart allograft recipients were assessed. Cellular rejection and vasculitis were diagnosed through histological analysis, and antibody-mediated rejection was performed with immunohistochemical C4d staining. The transcripts of ICAM, VCAM, VEGF, CCL2, IFNG, TGFB, TNF, ADIPOR1, and ADIPOR2 genes were examined through quantitative polymerase chain reaction using B2M for normalization. RESULTS: We observed a higher prevalence of severe vasculitis in the early period of post-transplant, and recovery was observed to take place around 1 year post-transplant. Additionally, vasculitis was found to be directly associated with acute cellular rejection and antibody-mediated rejection. The intense C4d capillary positivity predicts higher long-term cardiovascular disease mortality. In comparison with the vasculitis-free group, the group with severe vasculitis displayed reduced left ventricular ejection fraction and an upregulation of VCAM and IFNG associated with the downregulation of VEGF, ADIPOR1, and ADIPOR2. CONCLUSION: The vasculitis associated with the presence of C4d and the change in intragraft gene expression profile may contribute to poor allograft outcomes.

Down regulation of protective genes is associated with cellular and antibody-mediated rejection.

Despite advances in immunosuppressive therapy, rejection still remains the main obstacle to a successful transplant. This study aims to explore the gene expression profile of the rejection process in order to decrease the number of unnecessary endomyocardial biopsies in stable patients. METHODS: A total of 300 formalin-fixed and paraffin-embedded (FFPE) endomyocardial biopsies sampled from 63 heart allograft recipients were included in this study. Acute cellular rejection (ACR) and antibody-mediated rejection (AMR) were diagnosed by histological analysis and immunohistochemical C4d staining, respectively. Analysis of gene expression was performed by quantitative real-time polymerase chain reaction. The samples were grouped according to the ISHLT rejection classification, aiming the statistical analysis. RESULTS: There was a significant decrease in the HMOX1, AIF1, and CCL2 transcript over the post-transplantation period in non-rejection group (P<.001). Furthermore, the ADIPOR1, ADIPOR2, BCL2L1, and VEGFA protective genes were significantly downregulated in the ACR group (P<.05). ADIPOR2, BCL2L1, IL6, and NOS2 genes were also significantly downregulated in the AMR group than in the non-rejection group (P<.05). CONCLUSION: The downregulations of the protective genes contribute to the allograft rejection, and the archived FFPE samples are useful for the gene expression analysis aiming the allograft rejection surveillance.

Down regulation of protective genes is associated with cellular and antibody- mediated rejection

Despite advances in immunosuppressive therapy, rejection still remains the main obstacleto a successful transplant. This study aims to explore the gene expression profileof the rejection process in order to decrease the number of unnecessary endomyocardialbiopsies in stable patients. Methods: A total of 300 formalin- fixed and paraffin- embedded (FFPE) endomyocardialbiopsies sampled from 63 heart allograft recipients were included in this study. Acute cellular rejection (ACR) and antibody- mediated rejection (AMR) were diagnosedby histological analysis and immunohistochemical C4d staining, respectively. Analysisof gene expression was performed by quantitative real- time polymerase chain reaction.The samples were grouped according to the ISHLT rejection classification, aimingthe statistical analysis. Results: There was a significant decrease in the HMOX1, AIF1, and CCL2 transcriptover the post- transplantation period in non- rejection group (P<.001). Furthermore, the ADIPOR1, ADIPOR2, BCL2L1, and VEGFA protective genes were significantly downregulatedin the ACR group (P<.05). ADIPOR2, BCL2L1, IL6, and NOS2 genes were alsosignificantly downregulated in the AMR group than in the non- rejection group (P<.05). Conclusion: The downregulations of the protective genes contribute to the allograftrejection, and the archived FFPE samples are useful for the gene expression analysisaiming the allograft rejection surveillance.

"Non Working Beating Heart": novo método de proteção miocárdica no transplante cardíaco / Non Working Beating Heart: a new strategy of myocardial protection during heart transplant

INTRODUÇÃO E OBJETIVO: Trata-se do implante em posição ortotópica bicaval bipulmonar do coração doado batendo em normotermia. Este estudo busca diminuir o tempo isquêmico e criar condições de ir se adaptando ao organismo hospedeiro. MÉTODOS: Já em CEC, a primeira anastomose a ser feita é a da aorta, reperfundindo as artérias coronárias e recuperando os batimentos. As restantes são realizadas com o coração batendo em ritmo sinusal, sendo a da artéria pulmonar a última. Esta metodologia foi aplicada em 10 pacientes receptores, sendo oito do sexo masculino, com idades entre 16 e 69 (média de 32,7 anos), PSAo 90-100 (média de 96 mmHg), PSAP 25-65 (média de 46,1 mmHg), RVP 0,9-5,0 (média de 3,17 Wood), GTP 4-13 (média de 7,9 mmHg). Entre os 10 doadores, sete eram do sexo masculino, com idade entre 15 e 48 (média 27,7 anos), peso entre 65 e 114 kg (média de 83,1 kg). As causas do coma encefálico foram: TCE (cinco), AVCH (quarto) e tumor cerebral (um). RESULTADOS: O tempo isquêmico variou de 58 a 90 minutos (média 67,6 minutos), sendo que oito doadores estavam em hospitais da região metropolitana de São Paulo e dois em cidades distantes. Todos os enxertos, após completadas as anastomoses, retomaram o fluxo e o débito, mantendo bons parâmetros, com baixa dosagem de inotrópico e mantiveram estas condições no pós-operatório imediato. Não ocorreram óbitos e todos os pacientes obtiveram alta hospitalar. A evolução tardia variou de 20 dias a 10 meses, tendo ocorrido um óbito ao 4º mês pós-transplante, por sepse. CONCLUSÕES: Esta metodologia, além de reduzir o tempo isquêmico, permite ao órgão doado recuperar e manter seus batimentos sem pré nem pós-carga durante o implante, o que enseja proporcionar recuperação fisiológica, ultraestrutural, imunológica, inflamatória e mecânica do enxerto, com resultados consistentes precoces e tardios.

BACKGROUND AND OBJECTIVE: We attempt to reduce the ischemic time during implantation of the donor heart in the bicaval bipulmonary orthotopic position using normothermic beating heart and thus, facilitate the transplanted heart adaptation to the recipient. This study presents a small experience about a new strategy of myocardial protection during heart transplant. METHODS: In cardiopulmonary bypass, the aorta anastomosis was done first, allowing the coronary arteries to receive blood flow and the recovering of the beats. The rest of the anastomosis is performed on a beating heart in sinus rhythm. The pulmonary anastomosis is the last to be done. This methodology was applied in 10 subjects: eight males, age 16-69 (mean 32.7 years), SPAo 90-100 mmHg (mean 96 mmHg), SPAP 25-65 mmHg (mean 46.1 mmHg), PVR 0.9 to 5.0 Wood (mean 3.17 Wood), GTP 4-13 mmHg (mean 7.9 mmHg), and eight male donors, age 15-48 years (mean 27.7 years), weight 65-114 kg (mean 83.1 kg). Causes of brain coma: encephalic trauma in five hemorrhagic stroke in four, and brain tumor in one. RESULTS: The ischemic time ranged from 58-90 minutes (mean 67.6 minutes) and 8 donors were in hospitals of Sao Paulo and two in distant cities. All grafts assumed the cardiac output requiring low-dose inotropic therapy and maintained these conditions in the postoperative period. There were no deaths and all were discharged. The late evolution goes from 20 days to 10 months with one death occurred after 4 months due to sepsis. CONCLUSION: This method, besides reducing the ischemic time of the procedure, allows the donated organ to regain and maintain their beats without pre or after load during implantation entailing the physiological recovery of the graft.

Vasculites e eosinófilos em biópsia endomiocárdica, como preditores de rejeição em transplante cardíaco / Vasculitides and eosinophils in emdomyocardial biopsies as rejection predictors in heart transplantation / Vasculitis y eosinófilos en biopsia endomiocárdica, como predictores de rechazo en transplante cardíaco

FUNDAMENTO: O significado clínico de vasculites, lesões isquêmicas, efeito Quilty e da presença de eosinófilos em biópsias endomiocárdicas de receptores de transplante cardíaco com rejeições leves não foi ainda estabelecido. OBJETIVO: Verificar se esses achados histológicos encontrados nas biópsias endomiocárdicas (eosinófilos, vasculites, efeito Quilty e lesões isquêmicas) são capazes de predizer rejeição aguda do enxerto. MÉTODOS: Foram reavaliadas 1.012 biópsias endomiocárdicas consecutivas; dessas, 939 foram classificadas como OR ou 1R pela Nomenclatura da Sociedade Internacional de Transplante de Coração e Pulmão de 2005, e divididas em dois grupos: (1) Biópsias preditoras: aquelas que precederam rejeição aguda; e (2) Biópsias não preditoras: aquelas que não precederam rejeição aguda. Comparamos a ocorrência dos seguintes achados histológicos: vasculites, lesões isquêmicas, efeito Quilty e eosinófilos por análise uni e multivariada entre os grupos. RESULTADOS: Após análise estatística verificou-se a presença de vasculite intensa e de eosinófilos como maiores preditores para rejeição aguda futura, apresentando respectivamente as seguintes razões de chance: 10,60 (IC95 por cento: 3,62 - 31,06. p < 0,001) e 6,26 (IC95 por cento: 3,16 - 12,43. p < 0,001). CONCLUSÃO: Vasculites intensas e eosinófilos em biópsias do miocárdio são os principais fatores preditores de rejeição aguda pós-transplante cardíaco.

BACKGROUND: The clinical significance of vasculitides, ischemic lesions, Quilty effect and the presence of eosinophils in endomyocardial biopsies of heart transplantation recipients with mild rejection has yet to be established. OBJECTIVE: To verify whether these histological findings observed in endomyocardial biopsies (eosinophils, vasculitides, Quilty effect and ischemic lesions) are capable of predicting acute graft rejection. METHODS: A total of 1,012 consecutive endomyocardial biopsies were reevaluated; of these, 939 were classified as OR or 1R according to the Nomenclature of the International Society of Heart and Lung Transplantation of 2005 and divided in two groups: (1) Predictive biopsies: those that preceded acute rejection; and (2) Nonpredictive biopsies: those that did not precede acute rejection. We compared the occurrence of the following histological findings: vasculitides, ischemic lesions, Quilty effect and eosinophils between the groups by uni- and multivariate analyses. RESULTS: The statistical analysis showed that the presence of severe vasculitides and eosinophils were the best predictors for future acute rejection, with the following odds ratios: 10.60 (95 percentCI: 3.62 - 31.06. p < 0.001) and 6.26 (95 percentCI: 3.16 - 12.43, p < 0.001). CONCLUSION: Severe vasculitides and eosinophils in myocardial biopsies are the main predictive factors of acute graft rejection post-heart transplantation.

FUNDAMENTO: El significado clínico de vasculitis, lesiones isquémicas, efecto Quilty y de la presencia de eosinófilos en biopsias endomiocárdicas de receptores de transplante cardíaco con rechazos leves no fue aun establecido. OBJETIVO: Verificar si esos hallazgos histológicos encontrados en las biopsias endomiocárdicas (eosinófilos, vasculitis, efecto Quilty y lesiones isquémicas) son capaces de predecir rechazo agudo del injerto. MÉTODOS: Fueron reevaluadas 1.012 biopsias endomiocárdicas consecutivas; de esas, 939 fueron clasificadas como OR o 1R por la Nomenclatura de la Sociedad Internacional de Transplante de Corazón y Pulmón de 2005, y divididas en dos grupos: (1) Biopsias predictoras: aquellas que precedieron rechazo agudo; y (2) Biopsias no predictoras: aquellas que no precedieron rechazo agudo. Comparamos la ocurrencia de los siguientes hallazgos histológicos: vasculitis, lesiones isquémicas, efecto Quilty y eosinófilos por análisis uni y multivariado entre los grupos. RESULTADOS: Después de análisis estadístico se verificó la presencia de vasculitis intensa y de eosinófilos como mayores predictores para rechazo agudo futuro, presentando respectivamente las siguientes razones de posibilidad: 10,60 (IC95 por ciento: 3,62 - 31,06. p < 0,001) y 6,26 (IC95 por ciento: 3,16 - 12,43. p < 0,001). CONCLUSIÓN: Vasculitis intensas y eosinófilos en biopsias del miocardio son los principales factores predictores de rechazo agudo post transplante cardíaco.

Vasculitides and eosinophils in endomyocardial biopsies as rejection predictors in heart transplantation.

BACKGROUND: The clinical significance of vasculitides, ischemic lesions, Quilty effect and the presence of eosinophils in endomyocardial biopsies of heart transplantation recipients with mild rejection has yet to be established. OBJECTIVE: To verify whether these histological findings observed in endomyocardial biopsies (eosinophils, vasculitides, Quilty effect and ischemic lesions) are capable of predicting acute graft rejection. METHODS: A total of 1,012 consecutive endomyocardial biopsies were reevaluated; of these, 939 were classified as OR or 1R according to the Nomenclature of the International Society of Heart and Lung Transplantation of 2005 and divided in two groups: (1) Predictive biopsies: those that preceded acute rejection; and (2) Nonpredictive biopsies: those that did not precede acute rejection. We compared the occurrence of the following histological findings: vasculitides, ischemic lesions, Quilty effect and eosinophils between the groups by uni- and multivariate analyses. RESULTS: The statistical analysis showed that the presence of severe vasculitides and eosinophils were the best predictors for future acute rejection, with the following odds ratios: 10.60 (95%CI: 3.62 - 31.06. p < 0.001) and 6.26 (95%CI: 3.16 - 12.43, p < 0.001). CONCLUSION: Severe vasculitides and eosinophils in myocardial biopsies are the main predictive factors of acute graft rejection post-heart transplantation.

Cardiomiopatia dilatada / Dilated cardiomyopathy

A cardiomiopatia dilatada é a doença do miocárdio mais comum, sendo responsável por 25 por cento dos casos de insuficiência cardíaca, é a terceira causa mais comum de falência miocárdica e a indicação mais comum de transplante cardíaco na América do Norte. A cardiomiopatia dilatada (CMD) é caracterizada principalmente pela disfunção sistólica do ventrículo esquerdo, com aumento associado da massa e do volume. Várias doenças podem cusar CMD, porém em muitos casos, não se encontra nenhuma etiologia e a cardiomiopatia é chamada de idiopática (até 50 por cento dos casos).

The dilated cardiomyopathy is the most important myocardial disease and represent 25% of all heart diseases. It is the third cause of myocardial failure and the most common cause of heart transplantation in North America. Its feature is the left ventricle systolic dysfunction with mass and volume increase. Several diseases may cause dilated cardiomyopathy, but in 50% the cause is unknown.

Non Working Beating Heart: a new strategy of myocardial protection during heart transplant.

BACKGROUND AND OBJECTIVE: We attempt to reduce the ischemic time during implantation of the donor heart in the bicaval bipulmonary orthotopic position using normothermic beating heart and thus, facilitate the transplanted heart adaptation to the recipient. This study presents a small experience about a new strategy of myocardial protection during heart transplant. METHODS: In cardiopulmonary bypass, the aorta anastomosis was done first, allowing the coronary arteries to receive blood flow and the recovering of the beats. The rest of the anastomosis is performed on a beating heart in sinus rhythm. The pulmonary anastomosis is the last to be done. This methodology was applied in 10 subjects: eight males, age 16-69 (mean 32.7 years), SPAo 90-100 mmHg (mean 96 mmHg), SPAP 25-65 mmHg (mean 46.1 mmHg), PVR 0.9 to 5.0 Wood (mean 3.17 Wood), GTP 4-13 mmHg (mean 7.9 mmHg), and eight male donors, age 15-48 years (mean 27.7 years), weight 65-114 kg (mean 83.1 kg). Causes of brain coma: encephalic trauma in five hemorrhagic stroke in four, and brain tumor in one. RESULTS: The ischemic time ranged from 58-90 minutes (mean 67.6 minutes) and 8 donors were in hospitals of Sao Paulo and two in distant cities. All grafts assumed the cardiac output requiring low-dose inotropic therapy and maintained these conditions in the postoperative period. There were no deaths and all were discharged. The late evolution goes from 20 days to 10 months with one death occurred after 4 months due to sepsis. CONCLUSION: This method, besides reducing the ischemic time of the procedure, allows the donated organ to regain and maintain their beats without pre or after load during implantation entailing the physiological recovery of the graft.

Vasculitides and eosinophils in emdomyocardial biopsies as rejection predictors in heart transplantation

Background: The clinical significance of vasculitides, ischemic lesions, Quilty effect and the presence of eosinophils inendomyocardial biopsies of heart transplantation recipients with mild rejection has yet to be established.Objective: To verify whether these histological findings observed in endomyocardial biopsies (eosinophils, vasculitides, Quilty effect and ischemic lesions) are capable of predicting acute graft rejection. Methods: A total of 1,012 consecutive endomyocardial biopsies were reevaluated; of these, 939 were classified as OR or 1R according to the Nomenclature of the International Society of Heart and Lung Transplantation of 2005 and divided intwo groups: (1) Predictive biopsies: those that preceded acute rejection; and (2) Nonpredictive biopsies: those that did not precede acute rejection. We compared the occurrence of the following histological findings: vasculitides, ischemic lesions, Quilty effect and eosinophils between the groups by uni- and multivariate analyses.Results: The statistical analysis showed that the presence of severe vasculitides and eosinophils were the best predictorsfor future acute rejection, with the following odds ratios: 10.60 (95%CI: 3.62 - 31.06. p < 0.001) and 6.26 (95%CI: 3.16 - 12.43, p < 0.001). Conclusion: Severe vasculitides and eosinophils in myocardial biopsies are the main predictive factors of acute graftrejection post-heart transplantation.

Farmacologic pre implants test in high pulmonary hypertension and still in candidates for heterotopic transplantation.

BACKGROUND: Evaluation of pulmonary artery pressure just before transplanting with sodium nitroprusside may allow conversion to orthotopic technique. METHODS: Between 1992 and 2007, 228 transplants were performed systematically and this was used in seven patients with preoperative hemodynamic evaluation: Pre NP (mmHg) Post NP (mmHg) Systolic systemic blood pressure (PSAS) 108-78 (101.7 ± 10.9) 90-74 (79.5 ± 15.2) pulmonary arterial systolic pressure (PASP) 88-51 (69.8 ± 13.2) 70-40 (57.8 ± 9.9) Gradient transpulmonary (GTP) 16-11 (14.2 ± 1.7) 14-11 (12.4 ± 1.2) pulmonary vascular resistance (PVR/w) 7.9 to 4.8 (6.2 ± 1 0) 5.9-4.1 (5.0 ± 0.8). RESULTS: The intraoperative findings were: Pre NP (mmHg) e Post NP (mmHg), respectively, PSAS 91-78 (8.5 ± 5.2) and 65-59 (4.2 ± 63.8) (P = 0.017), decrease 19.9%, decrease 29.3%; PSAP 71-52 (61.8 ± 6.1) and 43-32 (37.5 ± 3.3) (P = 0.018), decrease 28%, decrease 41%. In light of these data, patients were transplanted by orthotopic technique not being observed mortality in the short and long-term evolution from 5 months to 6 years. CONCLUSION: This methodology allowed the conversion of the technique for heterotopic orthotopically, with good early and late outcomes.

Teste farmacológico pré-implante na hipertensão pulmonar elevada e fixa em candidatos a transplante heterotópico / Farmacologic test pre implants in hypertension pulmonary elevated and still in candidates to heterotopic transplantation

OBJETIVOS: Avaliar a pressão da artéria pulmonar, nos momentos que precedem ao transplante, e verificar se o nitroprussiato de sódio pode possibilitar a conversão para técnica ortotópica. MÉTODOS: Entre 1992 e 2007, foram realizados 228 transplantes e esta sistemática foi empregada em sete pacientes que apresentavam na avaliação hemodinâmica pré-operatória: Pré NP (mmHg) Pós NP (mmHg) Pressão Sistólica Arterial Sistêmica (PSAS) 108 - 78 (101,7 ±10,9) 90 - 74 (79,5 ± 15,2) Pressão Sistólica Arterial Pulmonar (PSAP) 88 - 51 (69,8 ± 13,2) 70 - 40 (57,8 ± 9,9) Gradiente Transpulmonar (GTP) 16 11 (14,2 ± 1,7) 14 - 11 (12,4 ± 1,2) Resistência Vascular Pulmonar (RVP/w) 7,9 - 4,8 (6,2 ± 1,0) 5,9 - 4,1 (5,0 ± 0,8). RESULTADOS: Os achados intra-operatórios foram: Pré NP (mmHg) e Pós NP (mmHg), repectivamente, PSAS 91-78 (8,5 ± 5,2) e 65-59 (63,8 ± 4,2) (P = 0,017), queda 19,9 por cento, Queda 29,3 por cento; PSAP 71-52 (61,8 ± 6,1) e 43-32 (37,5 ± 3,3) (P = 0,018), queda 28 por cento, Queda 41 por cento Diante destes dados, os pacientes foram transplantados pela técnica ortotópica, não sendo constatada mortalidade a curto e a longo prazo em evolução de 5 meses a 6 anos. CONCLUSÃO: A aplicação desta metodologia permitiu a conversão da técnica heterotópica para ortotópica, com bons resultados imediatos e tardios.

BACKGROUND: Evaluation of pulmonary artery pressure just before transplanting with sodium nitroprusside may allow conversion to orthotopic technique. METHODS: Between 1992 and 2007, 228 transplants were performed systematically and this was used in seven patients with preoperative hemodynamic evaluation: Pre NP (mmHg) Post NP (mmHg) Systolic systemic blood pressure (PSAS) 108-78 (101.7 ± 10.9) 90-74 (79.5 ± 15.2) pulmonary arterial systolic pressure (PASP) 88-51 (69.8 ± 13.2) 70-40 (57.8 ± 9.9) Gradient transpulmonary (GTP) 16-11 (14.2 ± 1.7) 14-11 (12.4 ± 1.2) pulmonary vascular resistance (PVR/w) 7.9 to 4.8 (6.2 ± 1 0) 5.9-4.1 (5.0 ± 0.8). RESULTS: The intraoperative findings were: Pre NP (mmHg) e Post NP (mmHg), respectively, PSAS 91-78 (8.5 ± 5.2) and 65-59 (4.2 ± 63.8) (P = 0.017), decrease 19.9 percent, decrease 29.3 percent; PSAP 71-52 (61.8 ± 6.1) and 43-32 (37.5 ± 3.3) (P = 0.018), decrease 28 percent, decrease 41 percent. In light of these data, patients were transplanted by orthotopic technique not being observed mortality in the short and long-term evolution from 5 months to 6 years. CONCLUSION: This methodology allowed the conversion of the technique for heterotopic orthotopically, with good early and late otcomes.

Vasculites e lesões isquêmicas imunomediadas como fatores preditores de mau prognóstico no transplante cardíaco / Imuno mediated vasculitis and ischemia as predictor factors of bad prognosis in cardiac transplantation

INTRODUÇÃO: O significado clínico das vasculites, lesões isquêmicas, efeito Quilty e da presença de eosinófilos em biópsias endomiocardicas de receptores de transplante cardíaco com rejeições leves não foi ainda estabelecido. OBJETIVOS: Verificar se estes achados histológicos encontrados nas biópsias endomiocardicas (eosinófilos, vasculites, efeito Quilty e lesões isquêmicas) são capazes de predizer rejeição aguda do enxerto acompanhada ou não de grave comprometimento hemodinâmico e morte por rejeição aguda. MÉTODOS: Foram reavaliadas 939 biópsias endomiocardicas consecutivas classificadas como OR ou 1R pela de 2005 da Nomenclatura da Sociedade Internacional de Transplante de Coração e Pulmão e dividimos estas em dois grupos (1) Biópsias preditoras: aquelas que precederam rejeição aguda, rejeição aguda associada à grave comprometimento hemodinâmico ou morte e (2) Biópsias não preditoras aquelas que não precederam eventos clínicos. Comparamos a ocorrência dos seguintes achados histológicos: vasculites, lesões isquêmicas, efeito Quilty e eosinófilos por análise uni e multivariada entre os grupos. RESULTADOS: Após análise estatística verificou-se que a presença de vasculite intensa e de eosinófilos como maiores preditores tanto para rejeição aguda futura, apresentando respectivamente as seguintes razões de chance: 10,60 (IC95%: 3,62 31,06. p<0,001) e 6,26 (IC95%:3,16 12,43. p< 0,001) , quanto para rejeição aguda associada á grave comprometimento hemodinâmico, que para este desfecho clínico apresentaram respectivamente as seguintes razões de chance 7,52 (IC95%: 1,45-38,93. p=0,016) e 6,61 (IC95%: 2,38 18,31. p< 0,001), e também para morte em decorrência a rejeição aguda com as respectivas razões de chance: 11,20 (IC95%: 3,53 36,17. p < 0, 001) e 14,50 (IC95%: 2,19 36,17. p = 0,006)...

INTRODUCTION: The clinical meaning of vasculitis, ischemic lesions, Quilty effect and the presence of eosinophils in endomyocardial biopsies of transplant recipients with mild rejections have not been established yet. OBJECTIVES: Verify if these histological findings (eosinophils, vasculitis, Quilty effect and ischemic lesions), whose clinical meaning remains unknown so far, are able to predict acute rejection of the transplanted organ, accompanied or not by severe hemodynamic compromise and death due to acute rejection. METHODS: We reevaluated 939 consecutive endomyocardial biopsies classified as 0R or 1R, according to the nomenclature that the International Society for Heart and Lung Transplantation established in 2005. We divided these biopsies in 2 groups, as they follow: (1) Predictor biopsies, which are preceded by acute rejection, acute rejection associated to severe hemodynamic compromise or death and (2) Non-predictor biopsies that did not precede any clinical events. We compared the occurrence of the histological findings studied (eosinophils, vasculitis, Quilty effect and ischemic lesions) through univariate and multivariate analysis among the groups. RESULTS: After an appropriate statistical analysis, the result obtained was the presence of intense vasculitis and eosinophils as the greatest predictors of future acute rejection, presenting the respective odds ratio: 10,60 (IC95%: 3,62 31,06. p<0,001) and 6,26 (IC95%:3,16 12,43. p< 0,001), as well as acute rejection associated to severe hemodynamic compromise, which presented the respective odds ratio for this clinical outcome: 7,52 (IC95%: 1,45-38,93. p=0,016) and 6,61 (IC95%: 2,38 18,31. p< 0,001) and death due to acute rejection, presenting the respective odds ratio: 11,20 (IC95%: 3,53 36,17. p < 0, 001) and 14,50 (IC95%: 2,19 36,17. p = 0,006)...