COVID-19 complicating perioperative management of LVAD implantation: A case report and systematic review.

The coronavirus 2019 disease (COVID-19) affected 125 million people worldwide and caused 2.7 million deaths. Some comorbidities are associated with worse prognosis and left ventricular assist device (LVAD) recipients are probably part of this high-risk population. We report a 31-year-old male patient who developed COVID-19 during LVAD implantation. His postoperative period was complicated by severe pneumonia and mechanical ventilation (MV) leading to right ventricular failure (RVF) and inotrope necessity. He experienced multiple complications, but eventually recovered. We present a systematic review of LVAD recipients and COVID-19. Among 14 patients, the mean age was 62.7 years, 78.5% were male. A total of 5 patients (35.7%) required MV and 3 patients (21.4%) died. A total of 2 patients (14.2%) had thromboembolic events. This case and systematic review suggest LVAD recipients are at particular risk of unfavorable outcomes and they may be more susceptible to RVF in the setting of COVID-19, particularly during perioperative period.

A medical epopee: recurrent fungal endocarditis, heart transplantation and chylopericardium.

BACKGROUND: Candida prosthetic endocarditis is associated with high mortality rates and valve replacement surgery, together with antifungal treatment, play a major role in eradicating the fungal infection. Valve reoperations in these scenarios may be relatively common due to the high infection relapse rates and, in some cases, heart transplantation may be an imposing therapy for infection resolution and for the heart failure related to the myocardial reoperation injury. Among the many postoperative complications related to heart transplantation, chylopericardium is a rare but challenging example. CASE PRESENTATION: We report the case of a 55-year-old man who was admitted to our hospital with a 1-month history of progressive dyspnea and fatigue. His past medical history included four open-heart surgeries for aortic and mitral valve replacement due to recurrent Candida parapsilosis infective endocarditis. Transthoracic echocardiogram showed a markedly reduced left ventricular systolic function and normofunctioning bioprosthetic valves. An inotropic dependency condition led to heart transplantation surgery. In the early postoperative period, a persistent chylous fluid started to drain from the pericardial tube, compatible with the diagnosis of chylopericardium. The lack of clinical response to total parenteral nutrition and intravenous infusion of octreotide imposed the need of interventional radiology with diagnostic lymphography through cisterna chyli puncture and thoracic duct catheterization, confirming the presence of a lymphatic fistula. A successful treatment outcome was achieved with percutaneous thoracic duct embolization using coils and n-butyl-cyanoacrilate glue, possibiliting hospital discharge. CONCLUSIONS: Fungal endocarditis requires combined treatment (surgical and antimicrobial) for eradication. Valve replacement, while necessary, may lead to severe ventricular deterioration and heart transplantation may be the only viable therapeutic solution. Among the several postoperative complications of heart transplantation, chylopericardium is an uncommon and defiant example. Advances in interventional radiology like the percutaneous embolization allow a less invasive and highly efficient approach for this complication.

Fluid overload after coronary artery bypass graft in patients on maintenance hemodialysis is associated with prolonged time on mechanical ventilation.

BACKGROUND: Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3-4) and patients with normal renal function (reference group). METHODS: This is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups according to time on mechanical ventilation: < 24 h, 24-48 h and > 48 h. The same observer followed patients daily from the surgery to the hospital discharge. Cumulative fluid balance was defined as the sum of daily fluid balance over the first 5 days following surgery. RESULTS: Patients requiring more than 48 h of ventilation (5.3%) had a lower estimated glomerular filtration rate, were more likely to be on maintenance dialysis, had longer anesthesia time, needed higher dobutamine and noradrenaline infusion following surgery, and had longer hospitalization stay. Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment in the day following surgery, and the renal function (normal, chronic kidney disease not on dialysis and maintenance hemodialysis) were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation. CONCLUSIONS: Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.

Whole-Genome Cardiac DNA Methylation Fingerprint and Gene Expression Analysis Provide New Insights in the Pathogenesis of Chronic Chagas Disease Cardiomyopathy.

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects 10 million people worldwide. Approximately 12000 deaths attributable to Chagas disease occur annually due to chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop CCC years after infection. Genetic mechanisms play a role in differential progression to CCC, but little is known about the role of epigenetic modifications in pathological gene expression patterns in CCC patients' myocardium. DNA methylation is the most common modification in the mammalian genome. Methods: We investigated the impact of genome-wide cardiac DNA methylation on global gene expression in myocardial samples from end-stage CCC patients, compared to control samples from organ donors. Results: In total, 4720 genes were differentially methylated between CCC patients and controls, of which 399 were also differentially expressed. Several of them were related to heart function or to the immune response and had methylation sites in their promoter region. Reporter gene and in silico transcription factor binding analyses indicated promoter methylation modified expression of key genes. Among those, we found potassium channel genes KCNA4 and KCNIP4, involved in electrical conduction and arrythmia, SMOC2, involved in matrix remodeling, as well as enkephalin and RUNX3, potentially involved in the increased T-helper 1 cytokine-mediated inflammatory damage in heart. Conclusions: Results support that DNA methylation plays a role in the regulation of expression of pathogenically relevant genes in CCC myocardium, and identify novel potential disease pathways and therapeutic targets in CCC.

Myocardial Infarction-Associated Transcript, a Long Noncoding RNA, Is Overexpressed During Dilated Cardiomyopathy Due to Chronic Chagas Disease.

Long noncoding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional, and posttranscriptional levels. Dysregulation of the lncRNA known as myocardial infarction-associated transcript (MIAT) has been associated with myocardial infarction. Chagas disease causes a severe inflammatory dilated chronic cardiomyopathy (CCC). We investigated the role of MIAT in CCC. A whole-transcriptome analysis of heart biopsy specimens and formalin-fixed, paraffin-embedded samples revealed that MIAT was overexpressed in patients with CCC, compared with subjects with noninflammatory dilated cardiomyopathy and controls. These results were confirmed in a mouse model. Results suggest that MIAT is a specific biomarker of CCC.

Severe and Moderate Primary Graft Dysfunction in Adult Heart Recipients.

INTRODUCTION: The aims of this study were to determine the incidence of severe and moderate primary graft dysfunction (PGD) in our center, to identify, retrospectively, donors' and recipients' risk factors for PGD development, and to evaluate the impact of PGD within 30 days after heart transplantation. METHODS: Donors' and recipients' medical records of 64 consecutive adult cardiac transplantations performed between January 2016 and June 2017 were reviewed. The International Society for Heart and Lung Transplantation (ISHLT) criteria were used to diagnose moderate and severe PGD. Associations of risk factors for combined moderate/severe PGD were assessed with appropriate statistical analyses. RESULTS: Sixty-four patients underwent heart transplantation in this period. Twelve recipients (18.7%) developed severe or moderate PGD. Development of PGD was associated with previous donor cardiopulmonary resuscitation and a history of prior heart surgery in the recipient (P=0.01 and P=0.02, respectively). The 30-day in hospital mortality was similar in both PGD and non-PGD patients. CONCLUSION: The use of the ISHLT criteria for PGD is important to identify potential risk factor. The development of PGD did not affect short-term survival in our study. More studies should be done to better understand the pathophysiology of PGD.

Symptomatic uterine leiomyomatosis with intracaval and intracardiac invasion: Video case report.

Background: Fibroid is the most prevalent benign tumor of the female genital tract. Intravenous and intracardiac leiomyomatosis (IVL and ICLM, respectively) are rare complications that present with symptoms of pulmonary thromboembolism and heart failure and whose etiology, despite controversial, is a direct vascular invasion by a primary uterine leiomyoma. Case presentation: We present the case of a 31-year-old female patient with a previous history of pelvic pain and dysmenorrhea, whose ultrasound showed an enlarged and heterogeneous uterus. Complete hysterectomy was performed, and the anatomopathological examination showed leiomyomas without evidence of malignancy. One month later, the patient manifested dyspnea and chest pain. A neoplastic thrombus was identified, extending from the inferior vena cava to the right atrium, for which we proceeded with cavo-atrial thrombectomy under Normothermic Cardiopulmonary Bypass (CPB) with Warm Blood Cardioplegia (WBC). A metastatic lung injury of non-malignant histology was also detected. Discussion: Uterine leiomyoma is a very common benign tumor of the female genital tract. IVL with ICLM are rare and difficult-to-treat complications, whose etiology is a direct vascular invasion by a primary uterine leiomyoma, although it is still controversial. The incidence of ICLM is 10 to 30% of IVL cases. The main symptoms of ICLM are dyspnea, syncope, edema of the lower extremities and palpitations. Treatment is based on complete surgical removal of the tumor thrombus. Studies demonstrated that the one-stage procedure is safer from the patient's perspective and that CPB with WBC reduced intraoperative blood loss and total operative time, ensuring a less traumatic postoperative. Conclusions: Most patients with uterine leiomyoma are asymptomatic and acute complications are rare. In ICLM clinical manifestations are related to heart failure and flow obstruction. Because of the severity of the condition and the curative potential of treatment, surgery is morbid but highly recommended. The use of CPB with WBC improved the postoperative period and increased the patient's quality of life.

Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens. / Sobrevida de Pacientes Transplantados Cardíacos com Doença de Chagas Sob Diferentes Regimes de Imunossupressores Antiproliferativos.

Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown. To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge ("Change" group). A p-value < 0.05 was considered statistically significant. Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates. This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.

A Doença de Chagas (DC) é uma causa importante de transplante cardíaco (TC). O principal obstáculo é a reativação da DC (RDC), normalmente associada a altas doses de imunossupressores. Estudos anteriores sugeriram uma associação do micofenolato de mofetila com aumento na RDC. No entanto, preditores de mortalidade são desconhecidos. Identificar os fatores de risco de mortalidade em pacientes com DC após o TC e o impacto do regime antiproliferativo sobre a sobrevida. Estudo retrospectivo com pacientes chagásicos submetidos ao TC entre janeiro de 2004 e setembro de 2020, em protocolo de imunossupressão que priorizava o uso de azatioprina e sua mudança para micofenolato de mofetila em caso de rejeição. Realizamos regressão univariada para identificar preditores de mortalidade e comparamos sobrevida, rejeição, e evidência RDC entre os pacientes que usavam azatioprina, micofenolato de mofetila, e aqueles que mudaram de azatioprina para micofenolato (grupo "Mudança") após a alta. Um valor de p<0,05 foi considerado estatisticamente significativo. Foram incluídos 85 pacientes, 54,1% homens, idade mediana 49 (39-57) anos, e 91,8% com prioridade na lista de espera. Dezenove (22,4%) usavam azatioprina, 37 (43,5%) micofenolato de mofetila, e 29 (34,1%) trocaram a terapia; a sobrevida não foi diferente entre os grupos, 2,9 (1,6-5,0) x 2,9 (1,8-4,8) x 4,2 (2,0-5,0) anos, respectivamente; p=0,4. Não houve diferença na taxa de rejeição (42%, 73% e 59% respectivamente; p=0,08) ou de RDC (T. cruzi positiva na biópsia endomiocárdica 5% x 11% x 7%; p=0,7; uso benzonidazol 58% x 65% x 69%; p=0,8; PCR positiva para T. cruzi 20% x 68% x 42% respectivamente; p=0,1). Este estudo retrospectivo com pacientes com DC e TC não mostrou diferença na sobrevida entre os diferentes regimes antiproliferativos. O uso de micofenolato de mofetila não foi associado com taxas significativamente mais altas de RDC ou rejeição do enxerto nesta coorte. Novos ensaios randomizados são necessários para abordar essa questão.

Matrix Metalloproteinase 2 and 9 Enzymatic Activities are Selectively Increased in the Myocardium of Chronic Chagas Disease Cardiomyopathy Patients: Role of TIMPs.

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.

Chronic thromboembolic pulmonary hypertension: the impact of advances in perioperative techniques in patient outcomes.

OBJECTIVES: Pulmonary endarterectomy (PEA) is the gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed at reporting outcomes of CTEPH patients undergoing PEA within 10 years, focusing on advances in anesthetic and surgical techniques. METHODS: We evaluated 102 patients who underwent PEA between January 2007 and May 2016 at the Instituto do Coração do Hospital das Clínicas da Universidade de São Paulo. Changes in techniques included longer cardiopulmonary bypass, heating, and cooling times and mean time of deep hypothermic circulatory arrest and shortened reperfusion time. Patients were stratified according to temporal changes in anesthetic and surgical techniques: group 1 (January 2007-December 2012), group 2 (January 2013-March 2015), and group 3 (April 2015-May 2016). Clinical outcomes were any occurrence of complications during hospitalization. RESULTS: Groups 1, 2, and 3 included 38, 35, and 29 patients, respectively. Overall, 62.8% were women (mean age, 49.1 years), and 65.7% were in New York Heart Association functional class III-IV. Postoperative complications were less frequent in group 3 than in groups 1 and 2: surgical complications (10.3% vs. 34.2% vs. 31.4%, p=0.035), bleeding (10.3% vs. 31.5% vs. 25.7%, p=0.047), and stroke (0 vs. 13.2% vs. 0, p=0.01). Between 3 and 6 months post-discharge, 85% were in NYHA class I-II. CONCLUSION: Improvements in anesthetic and surgical procedures were associated with better outcomes in CTEPH patients undergoing PEA during the 10-year period.

Heterotopic Heart Transplantation as a Left Ventricular Biological Assistance: a New Two-Stage Method Proposal.

Since Barnard's first heterotopic heart transplant in 1974, Copeland's method has been the greatest contribution to heterotopic transplants but has the drawback of donor's right ventricular atrophy. This new method proposes a modification in the anastomosis of the superior vena cava aiming to pre-serve donor's right ventricular function by decompressing the pulmonary territory and reducing the pulmonary arterial pressure, as a biological ventricular assist device. Finally, a second intervention is proposed, where a "twist" is performed to place the donor's heart in an orthotopic position after re-moval of the native heart. A pioneering research on this method received approval from the ethics committee of the Heart Institute of São Paulo. We believe that this method has the potential to im-prove quality of life in a selected group of patients.

Hypotheses, rationale, design, and methods for prognostic evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy who undergo medical or surgical treatment: MASS-VI (HF).

BACKGROUND: Ischemic cardiomyopathy and severe left ventricular dysfunction are well established to represent the main determinants of poor survival and premature death compared with preserved ventricular function. However, the role of myocardial revascularization as a therapeutic alternative is not known to improve the long-term prognosis in this group of patients. This study will investigate whether myocardial revascularization contributes to a better prognosis for patients compared with those treated with drugs alone and followed over the long term. METHODS: The study will include 600 patients with coronary artery disease associated with ischemic cardiomyopathy. The surgical or drug therapy option will be randomized, and the events considered for analysis will be all-cause mortality, nonfatal infarction, unstable angina requiring additional revascularization, and stroke. The events will be analyzed according to the intent-to-treat principle. Patients with multivessel coronary disease and left ventricular ejection fraction measurements of less than 35% will be included. In addition, myocardial ischemia will be documented by myocardial scintigraphy. Markers of myocardial necrosis will be checked at admission and after the procedure. DISCUSSION: The role of myocardial revascularization (CABG) in the treatment of patients with coronary artery disease and heart failure is not clearly established. The surgical option of revascularizing the myocardium is a procedure designed to reduce the load of myocardial hibernation in patients with heart failure caused by coronary artery disease. On the other hand, the assessment of myocardial viability is frequently used to identify patients with left ventricular ischemic dysfunction in which CABG may add survival benefit. However, the effectiveness of this option is uncertain. The great difficulty in establishing the efficacy of surgical intervention is based on the understanding of viability without ischemia. Thus, this study will include only patients with viable and truly ischemic myocardium to correct this anomaly. TRIAL REGISTRATION: Evaluation of a randomized comparison between patients with coronary artery disease associated with ischemic cardiomyopathy submitted to medical or surgical treatment: MASS-VI (HF), ISRCTN77449548, Oct 10th, 2019 (retrospectively registered).

Severe and Moderate Primary Graft Dysfunction in Adult Heart Recipients

ABSTRACT Introduction: The aims of this study were to determine the incidence of severe and moderate primary graft dysfunction (PGD) in our center, to identify, retrospectively, donors' and recipients' risk factors for PGD development, and to evaluate the impact of PGD within 30 days after heart transplantation. Methods: Donors' and recipients' medical records of 64 consecutive adult cardiac transplantations performed between January 2016 and June 2017 were reviewed. The International Society for Heart and Lung Transplantation (ISHLT) criteria were used to diagnose moderate and severe PGD. Associations of risk factors for combined moderate/severe PGD were assessed with appropriate statistical analyses. Results: Sixty-four patients underwent heart transplantation in this period. Twelve recipients (18.7%) developed severe or moderate PGD. Development of PGD was associated with previous donor cardiopulmonary resuscitation and a history of prior heart surgery in the recipient (P=0.01 and P=0.02, respectively). The 30-day in hospital mortality was similar in both PGD and non-PGD patients. Conclusion: The use of the ISHLT criteria for PGD is important to identify potential risk factor. The development of PGD did not affect short-term survival in our study. More studies should be done to better understand the pathophysiology of PGD.

Sobrevida de Pacientes Transplantados Cardíacos com Doença de Chagas Sob Diferentes Regimes de Imunossupressores Antiproliferativos / Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens

Resumo Fundamento A Doença de Chagas (DC) é uma causa importante de transplante cardíaco (TC). O principal obstáculo é a reativação da DC (RDC), normalmente associada a altas doses de imunossupressores. Estudos anteriores sugeriram uma associação do micofenolato de mofetila com aumento na RDC. No entanto, preditores de mortalidade são desconhecidos. Objetivos Identificar os fatores de risco de mortalidade em pacientes com DC após o TC e o impacto do regime antiproliferativo sobre a sobrevida. Métodos Estudo retrospectivo com pacientes chagásicos submetidos ao TC entre janeiro de 2004 e setembro de 2020, em protocolo de imunossupressão que priorizava o uso de azatioprina e sua mudança para micofenolato de mofetila em caso de rejeição. Realizamos regressão univariada para identificar preditores de mortalidade e comparamos sobrevida, rejeição, e evidência RDC entre os pacientes que usavam azatioprina, micofenolato de mofetila, e aqueles que mudaram de azatioprina para micofenolato (grupo "Mudança") após a alta. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Foram incluídos 85 pacientes, 54,1% homens, idade mediana 49 (39-57) anos, e 91,8% com prioridade na lista de espera. Dezenove (22,4%) usavam azatioprina, 37 (43,5%) micofenolato de mofetila, e 29 (34,1%) trocaram a terapia; a sobrevida não foi diferente entre os grupos, 2,9 (1,6-5,0) x 2,9 (1,8-4,8) x 4,2 (2,0-5,0) anos, respectivamente; p=0,4. Não houve diferença na taxa de rejeição (42%, 73% e 59% respectivamente; p=0,08) ou de RDC (T. cruzi positiva na biópsia endomiocárdica 5% x 11% x 7%; p=0,7; uso benzonidazol 58% x 65% x 69%; p=0,8; PCR positiva para T. cruzi 20% x 68% x 42% respectivamente; p=0,1). Conclusões Este estudo retrospectivo com pacientes com DC e TC não mostrou diferença na sobrevida entre os diferentes regimes antiproliferativos. O uso de micofenolato de mofetila não foi associado com taxas significativamente mais altas de RDC ou rejeição do enxerto nesta coorte. Novos ensaios randomizados são necessários para abordar essa questão.

Abstract Background Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown. Objectives To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. Methods Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge ("Change" group). A p-value < 0.05 was considered statistically significant. Results Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates. Conclusions This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.