Resultados Clínicos e Hemodinâmicos de Longo Prazo após o Transplante de Coração em Pacientes Pré-Tratados com Sildenafil / Long-Term Clinical and Hemodynamic Outcomes after Heart Transplantation in Patients Pre-Treated with Sildenafil

Resumo Fundamento A resistência vascular pulmonar elevada ainda é um grande problema na seleção de candidatos ao transplante cardíaco. Objetivo Nosso objetivo foi avaliar o efeito da administração de sildenafila pré-transplante cardíaco em pacientes com hipertensão pulmonar fixa. Métodos O estudo retrospectivo, de centro único, incluiu 300 candidatos a transplante cardíaco consecutivos tratados entre 2003 e 2013. Destes, 95 pacientes tinham hipertensão pulmonar fixa e, dentre eles, 30 pacientes foram tratados com sildenafila e acabaram passando pelo transplante, formando o Grupo A. O Grupo B incluiu 205 pacientes sem hipertensão pulmonar que passaram pelo transplante cardíaco. A hemodinâmica pulmonar foi avaliada antes do transplante, 1 semana e 1 ano após o transplante. A taxa de sobrevivência foi comparada entre os grupos. Neste estudo, um P valor < 0,05 foi considerado estatisticamente significativo. Resultados Após o tratamento com sildenafila, mas antes do TxC, a RVP (-39%) e a PAPs (-10%) diminuíram significativamente. A PAPs diminuiu após o TxC em ambos os grupos, mas permaneceu significativamente alta no grupo A em relação ao grupo B (40,3 ± 8,0 mmHg versus 36,5 ± 11,5 mmHg, P=0,022). Um ano após o TxC, a PAPs era 32,4 ± 6,3 mmHg no Grupo A versus 30,5 ± 8,2 mmHg no Grupo B (P=0,274). O índice de sobrevivência após o TxC 30 dias (97% no grupo A versus 96% no grupo B), 6 meses (87% versus 93%) e um ano (80% versus 91%) após o TxC não foi estatisticamente significativo (Log-rank P=0,063). Depois do primeiro ano, o índice de mortalidade era similar entre os dois grupos (sobrevivência condicional após 1 ano, Log-rank p=0,321). Conclusão Nos pacientes com HP pré-tratados com sildenafila, a hemodinâmica pós-operatória inicial e o prognóstico são numericamente piores em pacientes sem HP, mas depois de 1 ano, a mortalidade em médio e longo prazo são semelhantes. (Arq Bras Cardiol. 2021; 116(2):219-226)

Abstract Background Elevated pulmonary vascular resistance remains a major problem for heart transplant (HT) candidate selection. Objective This study sought at assess the effect of pre-HT sildenafil administration in patients with fixed pulmonary hypertension. Methods This retrospective, single-center study included 300 consecutive, HT candidates treated between 2003 and 2013, in which 95 patients had fixed PH, and of these, 30 patients were treated with sildenafil and eventually received a transplant, forming Group A. Group B included 205 patients without PH who underwent HT. Pulmonary hemodynamics were evaluated before HT, as well as 1 week after and 1 year after HT. Survival was compared between the groups. In this study, a p value < 0.05 was considered statistically significant. Results After treatment with sildenafil but before HT, PVR (-39%) and sPAP (-10%) decreased significantly. sPAP decreased after HT in both groups, but it remained significantly higher in group A vs. group B (40.3 ± 8.0 mmHg vs 36.5 ± 11.5 mmHg, p=0.022). One year after HT, sPAP was 32.4 ± 6.3 mmHg in group A vs 30.5 ± 8.2 mmHg in group B (p=0.274). The survival rate after HT at 30 days (97% in group A versus 96% in group B), at 6 months (87% versus 93%) and at one year (80% vs 91%) were not statistically significant (Log-rank p=0.063). After this first year, the attrition rate was similar among both groups (conditional survival after 1 year, Log-rank p=0.321). Conclusion In patients with severe PH pre-treated with sildenafil, early post-operative hemodynamics and prognosis are numerically worse than in patients without PH, but after 1 year, the medium to long-term mortality proved to be similar. (Arq Bras Cardiol. 2021; 116(2):219-226)

Primary graft failure after cardiac transplantation: prevalence, prognosis and risk factors.

OBJECTIVES: Primary graft failure (PGF) is a common and devastating complication, despite the advances in perioperative treatment. We aim to evaluate the prevalence of PGF and its impact on survival and to explore associated risk factors. METHODS: From November 2003 through December 2015, 290 patients submitted to cardiac transplantation were classified into non-PGF (243; 84%) and PGF (47; 16%) groups. The characteristics of the recipients were similar regarding age (54.6 ± 10.6 vs 54.0 ± 9.4 years; P = 0.74), male gender (78.2% vs 72.3%; P = 0.38) and transpulmonary gradient (9.4 ± 4.2 vs 10.5 ± 5.6 mmHg; P = 0.15); donors to the PGF group had similar age (35.5 ± 11.4 vs 37.5 ± 10.7 years; P = 0.27) but were predominantly female (21% vs 42.6%; P = 0.002). RESULTS: Mean ischaemic (89.0 ± 36.8 vs 103.3 ± 44.7 min; P = 0.019) and cardiopulmonary bypass (92.8 ± 14.5 vs 126.3 ± 62.4 min; P < 0.001) times were longer in the PGF group. Length of hospital stay was 13.5 ± 7.5 vs 28.9 ± 35.2 days (P= 0.005). Hospital mortality was 4.1% [1.6% for non-PGF and 17% for PGF (P < 0.001)]. Survival at 1, 5 and 10 years was 95.5 ± 1.3% vs 55.3 ± 7.3%, 84.1 ± 2.5% vs 47.4 ± 7.6% and 67.1 ± 3.8% vs 14.4 ± 12%, respectively (P < 0.001). Risk factors for PGF were female donor [odds ratio (OR): 2.56; 95% confidence interval (CI): 1.29-5.09; P = 0.007], total ischaemic time (OR: 1.01; 95% CI: 1.00-1.02; P = 0.032) and preoperative mechanical extracorporeal circulatory support (OR: 11.90; 95% CI: 2.62-54.12; P = 0.001). CONCLUSIONS: Our results demonstrate that PGF is associated with poor outcomes that extend beyond the 1st month and the 1st year after heart transplantation. We found female donor, total ischaemic time and preoperative mechanical extracorporeal circulatory support to be risk factors for PGF.

Heart transplantation: Early Results of Two Different Regimes of Immnunosuppression.

INTRODUCTION: The management of induction and maintenance immunosuppression therapy after heart transplantation (HT) remains a controversial issue. The dosage and the timing has been a changing target. We aimed at evaluate the incidence of acute cellular rejection (ACR) [≥1R grade], major infection and survival in first year after HT in patients receiving two different induction immunosuppression regimes and with a reduction in intensity of triple maintenance immunosuppression dose. METHODS: From November-2003 to June-2016, 317 patients were submitted to HT. After excluding those with pediatric age (n=8), those with previous renal or hepatic transplantation (n=2), those submitted to retransplantation (n=2), patients with early death without endomiocardial biopsy (n=10) and those in a transition maintenance regime (n=26), the study population resulted in 269 patients. These patients were divided in two groups: patients receiving the previous regime of two doses of basiliximab (group A, n=211) and those receiving a single dose of basiliximab (group B, n=58). All the patients were treated with a maintenance standard triple immunosuppressive regimen of corticosteroids, an inhibitor of calcineurin and mycophenolate mofetil but more immunosuppressive load in group A. RESULTS: Mean age of the recipients (group A vs. group B) was 54.6±10.6vs.55.0±9.8 years (p=0.808); 77.3%vs.75.9% were male (p=0.861); 28.4%vs.28.1% were diabetic (p=0.957); and ischemic etiology was present in 39.8%vs 41.0% of the patients (p=0.798), respectively. No differences were found, at first year, between the two groups concerning global ACR incidence (55.0%vs.56.9%, p=0.882, respectively) but major ACR (≥2R grade) was slightly superior in group B (16.6%vs.27.6%, p=0.080, respectively). Time-free from major ACR at 3rd, 6th and 12th months was, respectively 91.0±2.0%vs.84.5%±4.8%; 86.7±2.3%vs.74.1±5.7%; and 83.4±2.6%vs.72.4±5.9% (p=0.048). Time-free from major infection at 3rd, 6th and 12th months was, respectively 89.6±2.1%vs.82.8±5.0%; 87.7±2.3%vs.79.3±5.3%; and 84.4±2.5%vs.79.3±5.3% (p=0.253). No differences were found concerning survival at 3rd, 6th and 12th months (94.3±1.6%vs.94.8±2.9%; 92.4±1.8%vs.93.1±3.3%; and 90.0±2.1%vs.91.4±3.7%, (p=0.771) respectively). CONCLUSION: With this study, we verified that lowering doses of induction and maintenance therapy was responsible for increase cases of major ACR at first year of heart transplant. However, no differences were found concerning the incidence of major infection and early survival. Hence, effective immunosuppression induction regimen can apparently be done safely with a single dose regime without compromising survival at first year after HT.

Coronary Allograft Vasculopathy after Cardiac Transplantation: Prevalence, Prognostic and Risk Factors.

INTRODUCTION: Coronary allograft vasculopathy (CAV) is still a serious long-term complication after cardiac transplantation. PURPOSE: To evaluate the prevalence of CAV in a single institution, its impact on survival and to explore associated risk factors. METHODS: From November-2003 through June-2016, 316 patients were submitted to cardiac transplantation. After excluding those with paediatric age (n=8), those with previous renal or hepatic transplantation (n=2) and those who didn't survive the first year after cardiac transplantation (n=40), the study population resulted in 266 patients. Forty two patients (15.8%) with CAV, diagnosed by a new >50% coronary artery stenosis in any vessel during follow-up, were compared with a non-CAV group. RESULTS: Both groups share de same median age (54+10years). Recipient male sex predominated in the CAV group (93% vs. 74%), as did ischemic etiology (52% vs. 37%). Although not reaching statistical significance, CAV patients also had more dyslipidemia (60% vs. 50%), history of smoking (52% vs. 44%) and peripheral vascular disease (45% vs. 29%). The incidence of celular acute rejection 1R is more frequent in CAV group (69% vs. 60%) such as 2R or 3R (29% vs. 27%). Prolonged use of inotropic support and mechanical assistance after cardiac transplantation were comparable between both groups. The survival of this patients, who were submitted to cardiac transplantation and had lived at least 1 year, between CAV and non-CAV group was comparable at 5-year (91% vs. 85%), but tended to be lower for CAV patients in 10-year interval (52% vs. 73%). CONCLUSION: This data confirms CAV as a common long-term complication following cardiac transplantation. Although short to mid-term survival seems not to be affected by CAV, long-term survival appears lower, hence a longer follow-up is needed.

Heart Transplantation in Patients Older than 65 Years: Worthwhile or Wastage of Organs?

BACKGROUND: Patients older than 65 years have traditionally not been considered candidates for heart transplantation. However, recent studies have shown similar survival. We evaluated immediate and medium-term results in patients older than 65 years compared with younger patients. METHODS: From November 2003 to December 2013, 258 patients underwent transplantation. Children and patients with other organ transplantations were excluded from this study. Recipients were divided into two groups: 45 patients (18%) aged 65 years and older (Group A) and 203 patients (81%) younger than 65 years (Group B). RESULTS: Patients differed in age (67.0 ± 2.2 vs. 51.5 ± 9.7 years), but gender (male 77.8 vs. 77.3%; p = 0.949) was similar. Patients in Group A had more cardiovascular risk factors and ischemic cardiomyopathy (60 vs. 33.5%; p < 0.001). Donors to Group A were older (38.5 ± 11.3 vs. 34.0 ± 11.0 years; p = 0.014). Hospital mortality was 0 vs. 5.9% (p = 0.095) and 1- and 5-year survival were 88.8 ± 4.7 versus 86.8 ± 2.4% and 81.5 ± 5.9 versus 77.2 ± 3.2%, respectively. Mean follow-up was 3.8 ± 2.7 versus 4.5 ± 3.1 years. Incidence of cellular/humoral rejection was similar, but incidence of cardiac allograft vasculopathy was higher (15.6 vs. 7.4%; p = 0.081). Incidence of diabetes de novo was similar (p = 0.632), but older patients had more serious infections in the 1st year (p = 0.018). CONCLUSION: Heart transplantation in selected older patients can be performed with survival similar to younger patients, hence should not be restricted arbitrarily. Incidence of infections, graft vascular disease, and malignancies can be reduced with a more personalized approach to immunosuppression. Allocation of donors to these patients does not appear to reduce the possibility of transplanting younger patients.

A decade of cardiac transplantation in Coimbra: the value of experience.

INTRODUCTION AND OBJECTIVES: To analyze the experience gained in 10 years of the heart transplantation program of the University Hospital of Coimbra. METHODS: Between November 2003 and December 2013, 258 patients with a mean age of 53.0±12.7 years (3-72 years) and predominantly male (78%) were transplanted. Over a third of patients had ischemic (37.2%) and 36.4% idiopathic cardiomyopathy. The mean age of donors was 34.4±1.3 years and 195 were male (76%), with gender difference between donor and recipient in 32% of cases and ABO disparity (non-identical groups but compatible) in 18%. Harvest was distant in 59% of cases. In all cases total heart transplantation with bicaval anastomoses, modified at this center, was used. Mean ischemia time was 89.7±35.4 minutes. All patients received induction therapy. RESULTS: Early mortality was 4.7% (12 patients) from graft failure and stroke in five patients each, and hyperacute rejection in two. Thirteen patients (5%) required prolonged ventilation, 25 (11.8%) required inotropic support for more than 48 hours, and seven required pacemaker implantation. Mean hospital stay was 15.8±15.3 days (median 12 days). Ninety percent of patients were maintained on triple immunosuppressive therapy including cyclosporine, the remainder receiving tacrolimus. In 23 patients it was necessary to change the immunosuppression protocol due to renal and/or neoplastic complications and humoral rejection. All but two patients have been followed in the Surgical Center. Fifty patients (19.4%) subsequently died from infection (18), cancer (10), vascular (eight), neuropsychiatric (four), cardiac (two) or other causes (eight). Forty-six patients (17.8%) had episodes of cellular rejection (>2 R on the ISHLT classification), eight had humoral rejection (3.1%), and 22 have evidence of graft vascular disease (8.5%). Actuarial survival at 1, 5, and 8 years was 87±2%, 78±3% and 69±4%, respectively. CONCLUSION: This 10-year series yielded results equivalent or superior to those of centers with wider and longer experience, and have progressively improved following the introduction of changes prompted by experience. This program has made it possible to raise and maintain the rate of heart transplantation to values above the European average.

Results of heart transplantation in the urgent recipient - who should be transplanted? / Resultados do transplante cardíaco no paciente urgente - quem deve ser transplantado?

Objective: To evaluate immediate and long-term results of cardiac transplantation at two different levels of urgency. Methods: From November 2003 to December 2012, 228 patients underwent cardiac transplantation. Children and patients in cardiogenic shock were excluded from the study. From the final group (n=212), 58 patients (27%) were hospitalized under inotropic support (Group A), while 154 (73%) were awaiting transplantation at home (Group B). Patients in Group A were younger (52.0±11.3 vs. 55.2±10.4 years, P=0.050) and had shorter waiting times (29.4±43.8 vs. 48.8±45.2 days; P=0.006). No difference was found for sex or other comorbidities. Haemoglobin was lower and creatinine higher in Group A. The characteristics of the donors were similar. Follow-up was 4.5±2.7 years. Results: No differences were found in time of ischemia (89.1±37.0 vs. 91.5±34.5 min, P=0.660) or inotropic support (13.8% vs. 11.0%, P=0.579), neither in the incidence of cellular or humoral rejection and of cardiac allograft vasculopathy. De novo diabetes de novo in the first year was slightly higher in Group A (15.5% vs. 11.7%, P=0.456), and these patients were at increased risk of serious infection (22.4% vs. 12.3%, P=0.068). Hospital mortality was similar (3.4% vs. 4.5%, P=0.724), as well as long-term survival (7.8±0.5 vs. 7.4±0.3 years). Conclusions: The results obtained in patients hospitalized under inotropic support were similar to those of patients awaiting transplantation at home. Allocation of donors to the first group does not seem to compromise the benefit of transplantation. These results may not be extensible to more critical patients. .

Objetivo: Avaliar os resultados imediatos e de longo prazo do transplante cardíaco em dois níveis diferentes de urgência. Métodos: De novembro de 2003 a dezembro de 2012, 228 pacientes foram submetidos a transplante cardíaco. Crianças e os pacientes em choque cardiogênico foram excluídos do estudo. Do grupo final (n=212), 58 pacientes (27%) estavam hospitalizados e em suporte inotrópico (Grupo A), enquanto 154 (73%) aguardavam transplante em casa (Grupo B). Os pacientes do Grupo A eram mais jovens (52,0±11,3 vs. 55,2±10,4 anos, P=0,050) e tinham menor tempo de espera (29,4±43,8 vs. 48,8±45,2 dias, P=0,006). Não foram encontradas diferenças entre os sexos ou outras comorbidades. Níveis de hemoglobina foram menores e de creatinina superiores no Grupo A. As características dos doadores foram semelhantes. O acompanhamento foi de 4,5±2,7 anos. Resultados: Não foram observadas diferenças no tempo de isquemia (89,1 ± 37,0 vs. 91,5 ± 34,5 min, P=0,660) ou no suporte inotrópico (13,8% vs. 11,0%, P=0,579), nem na incidência de rejeição celular ou humoral e de vasculopatia do enxerto. Incidência de diabetes de novo no início do primeiro ano foi um pouco maior no Grupo A (15,5% vs. 11,7%, P=0,456), e esses pacientes apresentaram maior risco de infecção grave (22,4% vs. 12,3%, P=0,068). A mortalidade hospitalar foi semelhante (3,4% vs. 4,5%, P=0,724), bem como a sobrevida a longo prazo (7,8±0,5 vs. 7,4±0,3 anos). Conclusões: Os resultados obtidos em pacientes hospitalizados em suporte inotrópico foram semelhantes aos de pacientes que aguardam o transplante em casa. Alocação de doadores para o primeiro grupo não parece comprometer o benefício do transplante. Esses resultados podem não ser estendidos aos pacientes mais críticos. .

Gender mismatch between donor and recipient is a factor of morbidity but does not condition survival after cardiac transplantation.

We intended to evaluate the influence of sex mismatch between donor and recipient, which is still under much debate, on survival and comorbidities after cardiac transplantation. From November 2003 to December 2013, a total of 258 patients were transplanted in our center. From these, 200 receptors were male (77.5%) and constituted our study population, further divided into those who received the heart from a female donor (Group A) - 44 patients (22%) and those who received it from a male donor (Group B) - 156 (78%). Median follow-up was 4.2 ± 3.0 years (1-10 years). The two groups were quite comparable with each other, except for body mass index, systolic pulmonary artery pressure, and transpulmonary gradient, which were significantly lower in Group A. A low donor/recipient weigh ratio (<0.8) was avoided whenever possible. Hospital mortality was not different in the two groups. During follow-up, global survival was similar, as was survival free from acute cellular rejection and cardiac allograft vasculopathy. However, patients in Group A had decreased survival free from serious infections and malignant tumors. Allocation of female donors to male receptors can be done safely, at least in receptors without pulmonary hypertension and when an adequate donor/recipient weigh ratio is ensured.

Roles of Hedgehog pathway components and retinoic acid signalling in specifying zebrafish ventral spinal cord neurons.

In mouse, Hedgehog (Hh) signalling is required for most ventral spinal neurons to form. Here, we analyse the spinal cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signalling. We find that most V3 domain cells and motoneurons are lost, whereas medial floorplate still develops normally and V2, V1 and V0v cells form in normal numbers. This phenotype resembles that of mice that lack both Hh signalling and Gli repressor activity. Ventral spinal cord progenitor domain transcription factors are not expressed at 24 hpf in zebrafish MZsmo mutants. However, pMN, p2 and p1 domain markers are expressed at early somitogenesis stages in these mutants. This suggests that Gli repressor activity does not extend into zebrafish ventral spinal cord at these stages, even in the absence of Hh signalling. Consistent with this, ectopic expression of Gli3R represses ventral progenitor domain expression at these early stages and knocking down Gli repressor activity rescues later expression. We investigated whether retinoic acid (RA) signalling specifies ventral spinal neurons in the absence of Hh signalling. The results suggest that RA is required for the correct number of many different spinal neurons to form. This is probably mediated, in part, by an effect on cell proliferation. However, V0v, V1 and V2 cells are still present, even in the absence of both Hh and RA signalling. We demonstrate that Gli1 has a Hh-independent role in specifying most of the remaining motoneurons and V3 domain cells in embryos that lack Hh signalling, but removal of Gli1 activity does not affect more dorsal neurons.

Zebrafish V2 cells develop into excitatory CiD and Notch signalling dependent inhibitory VeLD interneurons.

The vertebrate spinal cord contains distinct classes of cells that form at precise dorsal-ventral locations and express specific combinations of transcription factors. In amniotes, V2 cells develop in the ventral spinal cord, just dorsal to motoneurons. All V2 cells develop from the same progenitor domain and hence are initially molecularly identical. However, as they start to become post-mitotic and differentiate they subdivide into two intermingled molecularly-distinct subpopulations of cells, V2a and V2b cells. Here we show that the molecular identities of V2a and V2b cells are conserved between zebrafish and amniotes. In zebrafish, these two cell types both develop into interneurons with very similar morphologies, but while V2a cells become excitatory Circumferential Descending (CiD) interneurons, V2b cells become inhibitory Ventral Lateral Descending (VeLD) interneurons. In addition, we demonstrate that Notch signalling is required for V2 cells to develop into V2b cells. In the absence of Notch signalling, all V2b cells develop as V2a cells.

A terceira idade e suas necessidades: uma visão de enfermagem / The aged client problems and the attendance of his needs

O trabalho do tipo exploratório, estuda o cliente idoso e suas necessidades humanas, o tipo de assistência de enfermagem oferecida aos clientes instittucionalizados e aos inseridos em situação domiciliar. O referencial teórico consta de 46 títulos entre periódicos, livros e teses. A metodologia utiliza instrumentos específicos (Roteiros de entrevista e questionário). Foram feitas 60 entrevistas com clientes idosos e 40 com pessoas prestadoras de assistência a esses clientes. Os resultados encontrados evidenciam que a assistência ao cliente idoso ainda não está sendo oferecida de forma adequada que atenda às necessidades humanas específicas da terceira idade, nos seus aspectos biológicos, psicológicos e espirituais. Os achados sugerem a continuação dos estudos abordando outros aspectos do problema, destacando-se: a educação de grupos para a assistência e a descoberta ou renovação de metodologias adequadas socio-psicológica de clientes na 3a idade.

Tipos de fracturas más frecuentes llevadas a la sala de reducción del Hospital Doctor Darío Contreras / Types of the fractures more common in the reduction room in the Hospital Dr. Darío Contreras

Se tomaron los casos de pacientes enviados a la sala de Reducción desde la emergencia del Hospital Doctor Darío Contreras, en el semestre comprendido del 1§ de Enero al 30 de Junio de 1984, con el fin de determinar el o los tipos de fracturas más frecuentes, además, la edad, sexo y tipo de anestésicos usados para la reducción de dichas fracturas. Pudimos determinar que el tipo más frecuente de fractura lo constituyó la fractura del 1/3 distal de cúbito y radio con 17.4% además que el sexo más frecuente fue el masculino con 62.7% y que prevaleció el uso de anestesia general en el tratamiento de éstos pacientes