Disección coronaria espontánea en paciente trasplantada de corazón / Spontaneous coronary artery dissection in a heart transplant patient: report of one case

Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome that predominantly affects women without cardiovascular risk factors. In transplant patients, spontaneous coronary artery dissection is an extremely rare condition, having been described in only three patients, in whom vascular damage secondary to the use of anticalcineurinics is postulated as a probable mechanism. We report a spontaneous coronary dissection in a female who received a heart transplant at 34 years of age. The diagnosis was made in a follow-up coronary angiography three years after transplantation, supplemented with optical coherence tomography. A percutaneous coronary revascularization of the involved artery was performed, with good immediate results and at one year of follow-up.

C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant

OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not.

Giant left atrium associated with massive thrombus formation 14 years after orthotopic heart transplantation

Abstract We report the case of a 60-year-old patient who underwent orthotopic heart transplant 14 years earlier. Routine echocardiography showed giant masses in the left atrium. There were no symptoms or thromboembolic events in the past. Magnetic resonance imaging study revealed very enlarged left atrium (8.7 × 10.6 cm) occupied by irregular smooth mass (7 × 5 × 6.1 cm) with a stalk that was attached to the posterior left atrial wall in the area of graft suture lines. Intraoperative examination revealed a massive thrombus (12 × 10 cm) that filled almost the entire left atrial area.

Heart Transplantation for Chagas Cardiomyopathy

Abstract Heart transplantation (HT) is an established treatment for patients with advanced heart failure (HF). Chagas disease (CD), caused by the Trypanosoma cruzi (T.cruzi) is an important cause of HF in Latin America. Considering CD is a chronic infectious disease, the use of immunosuppressive therapy after HT can reactivate T. cruzi infection and compromise outcomes. Early diagnosis and treatment of this complication is extremely important, which requires knowledge, experience, and a high degree of suspicion by transplant physicians. Furthermore, with the international immigration of people, CD is no longer exclusive to Latin America, since a large number of immigrants with T. cruzi infection are living in non-endemic countries. This phenomenon represents not only a new global epidemiological problem, but also a challenge for transplant teams. This review aims to discuss the peculiarities of HT in the context of CD, with a focus on reactivation of the infection, clinical manifestations, etiological treatment of T. cruzi and differential diagnosis with allograft rejection, among HT recipients.

Reactivation of Chagas disease in a heart transplant patient infected by sylvatic trypanosoma cruzi discrete typing unit I

Abstract Heart transplantation is an effective treatment for Chagas disease patients with severe cardiomyopathy. However, Trypanosoma cruzi reactivation is of great concern. The T. cruzi parasite is classified into six discrete typing units (DTUs identified as TcI-TcVI). It is unknown whether there is an association between T. cruzi genetic lineages and the different clinical manifestations of the disease. We report the case of a 51-year-old man who received a heart transplantation and presented with a reactivation of the disease. The molecular characterization of the parasite showed that the reactivation was related to specific infection by a DTU I (TcISYL) parasite.

Fatal case of donor-derived colistin-resistant carbapenemase-producing Klebsiella pneumoniae transmission in cardiac transplantation

ABSTRACT Herein we report a fatal case of donor-derived transmission of XDR-resistant carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) in cardiac transplantation. A 59-year-old male patient with non-obstructive hypertrophic cardiomyopathy underwent heart transplantation. On day 5 post-operation, blood cultures from the donor were positive for colistin-resistant carbapenemase-producing K. pneumoniae (ColR KPC-Kp) susceptible only to amikacin. Recipient blood cultures were also positive for ColR KPC-Kp with the same sensitivity profile as the donor isolate with an identical PFGE pattern. The patient was treated with double-carbapenems and amikacin. The patient evolved to pericarditis, osteomyelitis, and pulmonary necrosis, all fragment cultures positive for the same agent. The patient developed septic shock, multiple organ failure and died on day 50 post-transplantation. Based on current microbiological scenario worldwide the possibility of transmitting multidrug resistant (MDR) organisms should be considered.

Transmission of dengue virus from deceased donors to solid organ transplant recipients: case report and literature review

ABSTRACT Dengue fever is a vector-transmitted viral infection. Non-vectorial forms of transmission can occur through organ transplantation. We reviewed medical records of donors and recipients with suspected dengue in the first post-transplant week. We used serologic and molecular analysis to confirm the infection. Herein, we describe four cases of dengue virus transmission through solid organ transplantation. The recipients had positive serology and RT-PCR. Infection in donors was detected through serology. All cases presented with fever within the first week after transplantation. There were no fatal cases. After these cases, we implemented dengue screening with NS1 antigen detection in donors during dengue outbreaks, and no new cases were detected. In the literature review, additional cases had been published through August 2017. Transmission of Dengue virus can occur through organ donation. In endemic regions, it is important to suspect and screen for dengue in febrile and thrombocytopenic recipients in the postoperative period.

Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.

Enfermedad por citomegalovirus en pacientes receptores de trasplante de corazón en un centro de referencia nacional / Cytomegalovirus disease in post-heart-transplant patients at a national reference center

Introduction: Heart transplantation remains as the treatment of choice when the heart failure is refractory to the medical or surgical therapy. Therefore, cytomegalovirus disease is an important post-heart-transplant infectious complication. Aims: To describe the prevalence and clinical characteristics of the cytomegalovirus disease after heart transplant surgery. Materials and Methods: A retrospective, descriptive study was conducted. It enrolled 35 heart-transplant patients attended in the Cardiovascular National Institute (INCOR), between 2010 and 2015. The information was obtained through the review of medical records. The demographic and relevant clinical variables were analyzed for the cytomegalovirus disease cases. Results: The population mean age was 39.49 ± 15.07 years and most of them were male patients (63%). The prevalence of the cytomegalovirus disease was 5.7% (two patients), both were seronegative for cytomegalovirus before transplantation. One of the patients had the disease before finishing the valganciclovir prophylaxis and the other after the end of it. Conclusion: The prevalence of the cytomegalovirus disease is slightly lower than in other studies. Moreover, the cytomegalovirus disease can remit with a prompt diagnosis and the proper medical treatment.

Introducción: El trasplante cardiaco es el tratamiento de elección ante la falla cardiaca refractaria a la terapia médica o quirúrgica. En base a ello, la enfermedad por citomegalovirus (CMV) es una importante complicación infecciosa post-trasplante de corazón. Objetivos: Describir la prevalencia y las características clínicas de los pacientes que desarrollaron enfermedad por CMV posttrasplante de corazón. Materiales y Métodos: Se realizó un estudio retrospectivo y descriptivo, donde se incluyó a los 35 pacientes que recibieron trasplante de corazón en el Instituto Nacional Cardiovascular entre el período 2010-2015. La información se obtuvo mediante la revisión de historias clínicas. Se analizaron las variables demográficas y clínicas relevantes de los casos con enfermedad por CMV. Resultados: La edad media de la población fue de 39,49 ± 15,07 años, siendo la mayoría de sexo masculino (63%). La prevalencia de la enfermedad por CMV fue de 5,7%, -dos pacientes-, ambos con serología negativa para CMV previa al trasplante. Uno de ellos presentó la enfermedad antes de terminar la profilaxis con valganciclovir y el otro luego del cese de la misma. Conclusión: La prevalencia de la enfermedad por CMV es ligeramente menor que en otros estudios. Asimismo, ésta puede remitir con un pronto diagnóstico y el adecuado tratamiento médico.

Hypertension and arterial stiffness in heart transplantation patients

OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension.

Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients / Diagnóstico de Rejeição por Análise de Potenciais Ventriculares Tardios em Doentes Transplantados ao Coração

Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without). Results: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02). Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03) and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03). We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01), assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies.

Fundamento: A rejeição do transplante cardíaco origina zonas de condução lenta e fragmentada. O eletrocardiograma de alta resolução (ECGAR) é um método potencial de estratificação de risco da rejeição. Objetivo: Elaborar um escore de risco para rejeição, recorrendo ao ECGAR. Métodos: Estudaram-se 28 pacientes transplantados. Numa primeira fase, baseando-nos no diagnóstico de rejeição aguda, dividimos a amostra em dois grupos (5 pacientes com rejeição, 23 sem rejeição). Numa segunda fase, a divisão da amostra teve em conta o diagnóstico de rejeição em pelo menos uma biopsia realizada durante o seguimento (rejeição pm1) (18 pacientes com rejeição, 10 sem rejeição). Resultados: Para rejeição aguda, a única variável a revelar associação foi fibrose, evidenciando um aumento do risco de rejeição quando presente no ECG (OR = 19; IC 95% = 1,65-218,47; p = 0,02). Para rejeição pm1, constatamos que, para cada diminuição de unidade da RMS40, ocorre aumento de 7% do risco de rejeição (OR = 0,97; IC 95% = 0,87-0,99; p = 0,03) e que o aumento da LAS40 aumenta 1,06 vez o risco de rejeição (OR = 1,06; IC 95% = 1,01-1,11; p = 0,03). Formulamos um escore constituído por essas variáveis e aplicamos aos 28 indivíduos da amostra. A associação de fibrose, valores crescentes da LAS40 e valores decrescentes da RMS40 tem uma boa capacidade para distinguir doentes com e sem rejeição (AUC = 0,82; p < 0,01), assumindo um ponto de corte com sensibilidade = 83,3% e especificidade = 60%. Conclusão: O ECGAR distingue doentes com e sem rejeição. A utilidade do escore proposto deverá ser demonstrada em estudos de seguimento englobando uma amostra de maiores dimensões.

Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry / Terapia de Contrapulsação Aórtica em Pacientes com Insuficiência Cardíaca Avançada: Análise do Registro TBRIDGE

Abstract Background: The use of aortic counterpulsation therapy in advanced heart failure is controversial. Objectives: To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP) and its impact on 30-day mortality in patients with heart failure. Methods: Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). We analyzed changes in oxygen central venous saturation (ScvO2), arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test. Results: A total of 223 patients (mean age 49 ± 14 years) were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO2 (50.5% vs. 65.5%, p < 0.001) and use of nitroprusside (33.6% vs. 47.5%, p < 0.001), and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001) and use of vasopressors (36.3% vs. 25.6%, p = 0.003) after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008). Conclusion: After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation.

Resumo Fundamento: A utilização da terapia de contrapulsação aórtica na insuficiência cardíaca avançada é controversa. Objetivos: Avaliar o efeito hemodinâmico e metabólico do balão intra-aórtico (BIA) e seu impacto sobre a mortalidade em 30 dias em pacientes com insuficiência cardíaca. Métodos: Estudo prospectivo histórico, unicêntrico, avaliando todos os pacientes tratados com BIA entre agosto/2008 e julho/2013, incluídos em registro institucional denominado TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). Analisaram-se variações na saturação venosa central de oxigênio (SVO2), lactato arterial e uso de fármacos vasoativos 48 horas após instalação do dispositivo. A mortalidade em 30 dias foi estimada pelo método de Kaplan-Meier e diferenças entre subgrupos foram avaliadas pelo teste de Log-rank. Resultados: Foram incluídos 223 pacientes com idade média de 49 ± 14 anos, fração de ejeção do ventrículo esquerdo média de 24 ± 10%, sendo 30% acometidos por Doença de Chagas. Em comparação à pré-instalação do BIA, após a instalação, houve aumento da SVO2 (51% vs. 66%, p < 0,001) e no uso de nitroprussiato (34% vs. 48%, p < 0,001), além de redução do lactato (31 vs. 17 mg/dL, p < 0,001) e no uso de vasopressores (36% vs. 26%, p = 0,003). A sobrevida em 30 dias foi de 69%, com menor mortalidade nos pacientes chagásicos comparativamente aos não chagásicos (p = 0,008). Conclusão: Nas primeiras 48 horas de utilização, o BIA promoveu mudança no uso de fármacos vasoativos e melhora da perfusão tecidual. A etiologia chagásica associou-se a menor mortalidade em 30 dias. A terapia de contrapulsação aórtica mostrou-se opção eficaz de suporte circulatório em pacientes candidatos a transplante cardíaco.

Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation / Experiência na Utilização de ECMO na Disfunção Primária de Enxerto Pós-Transplante Cardíaco Ortotópico

Background:Primary graft dysfunction is the main cause of early mortality after heart transplantation. Mechanical circulatory support has been used to treat this syndrome.Objective:Describe the experience with extracorporeal membrane oxygenation to treat post-transplant primary cardiac graft dysfunction.Methods:Between January 2007 and December 2013, a total of 71 orthotopic heart transplantations were performed in patients with advanced heart failure. Eleven (15.5%) of these patients who presented primary graft dysfunction constituted the population of this study. Primary graft dysfunction manifested in our population as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe hemodynamic instability in the immediate postoperative period with severe cardiac dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia time was 151 ± 82 minutes. Once the diagnosis of primary graft dysfunction was established, we installed a mechanical circulatory support to stabilize the severe hemodynamic condition of the patients and followed their progression longitudinally.Results:The average duration of extracorporeal membrane oxygenation support was 76 ± 47.4 hours (range 32 to 144 hours). Weaning with cardiac recovery was successful in nine (81.8%) patients. However, two patients who presented cardiac recovery did not survive to hospital discharge.Conclusion:Mechanical circulatory support with central extracorporeal membrane oxygenation promoted cardiac recovery within a few days in most patients.

Fundamento:A disfunção primária de enxerto é a principal causa de mortalidade precoce após o transplante cardíaco. O uso de assistência circulatória mecânica tem sido empregado no tratamento dessa síndrome.Objetivo:Descrever a experiência com o uso de oxigenação por membrana extracorpórea para tratamento de disfunção primária de enxerto pós-transplante cardíaco.Métodos:Entre janeiro de 2007 e dezembro de 2013, foram realizados 71 transplantes cardíacos ortotópicos em pacientes com insuficiência cardíaca avançada. Destes, 11 (15,5%) pacientes apresentaram disfunção primária de enxerto, os quais constituíram a população deste estudo. As manifestações da disfunção primária de enxerto na nossa população foram falência no desmame da circulação extracorpórea em seis (54,5%) pacientes, instabilidade hemodinâmica grave no pós-operatório imediato com disfunção cardíaca acentuada em três (27,3%) e pós-parada cardíaca em dois (18,2%). O tempo de isquemia médio foi 151 ± 82 minutos. Assim que o diagnóstico de disfunção primária de enxerto foi estabelecido, procedeu-se à instalação de suporte circulatório mecânico para estabilização de quadro hemodinâmico grave, e a evolução dos pacientes foi estudada temporalmente.Resultados:A duração média de assistência em oxigenação por membrana extracorpórea foi 76 ± 47,4 horas (variação de 32 a 144 horas). O desmame com recuperação cardíaca obteve sucesso em nove (81,8%) pacientes. No entanto, dois pacientes, que tiveram recuperação cardíaca, não sobreviveram à alta hospitalar.Conclusão:O uso de assistência circulatória mecânica por meio de oxigenação por membrana extracorpórea central promoveu recuperação cardíaca em poucos dias na maioria dos pacientes.