Absolute Lymphocyte Count: a Predictor of Positive Serum PCR for Trypanosoma cruzi in Patients with Chagas Disease Undergoing Heart Transplantation. / Contagem Absoluta de Linfócitos: um Preditor de PCR Sérica Positiva para o Trypanosoma cruzi em Pacientes com Chagas Submetidos ao Transplante Cardíaco.

BACKGROUND: It is unknown whether lymphopenia is a risk factor for the reactivation of Chagas disease in heart transplantation (HTx), as recently described in the reactivation of cytomegalovirus in transplant patients. OBJECTIVE: To evaluate whether lymphopenia in the perioperative period of heart transplantation is related to early Trypanosoma cruzi parasitemia. METHODS: This observational, retrospective study analyzed a sample from January 2014 to January 2023). Parasitemia was evaluated in the first 3 months after HTx using serum polymerase chain reaction (PCR) and compared with the total lymphocyte count in the perioperative period of HTx using receiver operating characteristic curves. Baseline characteristics were compared with PCR for Chagas using independent Cox proportional hazards models. A significance level of 5% was adopted. RESULTS: The sample (n = 35) had a mean age of 52.5 ± 8.1 years, and 22 patients (62.8%) had positive PCR for Chagas. The mean lowest lymphocyte values in the first 14 days after HTx were 398 ± 189 and 755 ± 303 cells/mm3 in patients with and without parasitemia, respectively, within 3 months after HTx (area under the curve = 0.857; 95% confidence interval: 0.996 to 0.718, sensitivity and specificity of 83.3% and 86.4%). A cutoff value of less than 550 lymphocytes/mm3 was determined as a risk factor for the presence of parasitemia. Patients with lymphocytes < 550 units/mm3 in the first 14 days after HTx presented positive PCR in 80% of cases. For every increase of 100 lymphocytes/mm3, the risk of PCR positivity was reduced by 26% (hazard rate ratio = 0.74; 95% confidence interval: 0.59 to 0.93, p = 0.009). CONCLUSION: There was an association between lymphopenia in the perioperative period of HTx and early T. cruzi parasitemia detected by PCR.

FUNDAMENTO: É desconhecido se a linfopenia é fator de risco para a reativação da doença de Chagas no transplante cardíaco (TxC), como recentemente descrito na reativação de citomegalovírus em pacientes transplantados. OBJETIVO: Avaliar se a linfopenia no perioperatório do TxC está relacionada à parasitemia precoce pelo Trypanosoma cruzi. MÉTODOS: Amostra analisada (janeiro de 2014 a janeiro de 2023) em estudo observacional e retrospectivo. A parasitemia foi avaliada nos primeiros 3 meses após o TxC por meio da reação em cadeia da polimerase sérica (PCR) e comparada com a contagem total de linfócitos no perioperatório do TxC por curvas ROC. Comparadas características de base com a PCR Chagas por modelos de risco proporcionais de Cox independentes. Nível de significância adotado de 5%. RESULTADOS: Amostra (n = 35) apresentou idade média de 52,5 ± 8,1 anos e PCR Chagas positiva em 22 pacientes (62,8%). As médias dos menores valores de linfócitos nos primeiros 14 dias do TxC foram 398 ± 189 e 755 ± 303 células/mm3 em pacientes com e sem parasitemia nos 3 meses após o TxC, respectivamente (área sob a curva = 0,857; intervalo de confiança de 95%: 0,996 a 0,718, sensibilidade e especificidade de 83,3% e 86,4%). Determinado valor de corte inferior a 550 linfócitos/mm3 como fator de risco para presença de parasitemia. Pacientes com linfócitos < 550 unidades/mm3 nos primeiros 14 dias do pós-TxC apresentaram PCR positiva em 80% dos casos. Para cada aumento de 100 linfócitos/mm3, o risco de positividade da PCR é reduzido em 26% (razão de riscos = 0,74; intervalo de confiança de 95%: 0,59 a 0,93, p = 0,009). CONCLUSÃO: Houve associação entre a linfopenia no perioperatório do TxC com a parasitemia precoce pelo T. cruzi detectada por PCR.

Chagas Cardiomyopathy and Myocardial Sympathetic Denervation.

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.

Survival after heart transplantation for Chagas cardiomyopathy using a conventional protocol: A 10-year experience in a single center.

BACKGROUND: Heart transplant (HT) remains the most frequently indicated therapy for patients with end-stage heart failure that improves prognosis in Chagas cardiomyopathy (CCM). However, the lack of benznidazole therapy and availability of RT-PCR follow-up in many centers is a major limitation to perform this life-saving intervention, as there are concerns related with the risk of reactivation. We aimed to describe the outcomes of a cohort of patients with CCM who underwent HT using a conventional protocol with mycophenolate mofetil, without benznidazole prophylaxis or RT-PCR follow-up. METHODS: Retrospective cohort study. Between 2008 and 2018, 43 patients with CCM underwent HT. A descriptive analysis to characterize outcomes as rejection, infectious and neoplastic complications and a survival analysis was carried out. RESULTS: Median of follow-up was 4.3 (IR 4.28) years. Survival at 1 month, 1 year, and 5 years was 95%, 85%, and 75%, respectively, infections being the main cause of death (60%). Reactivations occurred in only three patients (7.34%) and were not related to mortality. CONCLUSION: This cohort showed a favorable survival and a low reactivation rate without an impact on mortality. Our results suggest that performing HT in patients with CCM following conventional guidelines and recommendations for other etiologies is a safe approach.

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.

Renal denervation in patients with heart failure secondary to Chagas' disease: A pilot randomized controlled trial.

INTRODUCTION: Chagas disease is one of the most relevant endemic parasitic diseases in Latin America, affecting approximately 6 million people. Overt Chagas heart disease is an ominous condition, occurring in 20-30% of infected individuals, which has besides the persistent myocarditis a peculiar intracardiac ganglionic neuronal depletion and dysautonomy. This study aims to evaluate the safety and feasibility of renal denervation for patients with advanced symptomatic Chagas cardiomyopathy. METHODS: Open-label prospective pilot study that randomized patients with Chagas heart disease to either renal denervation or conservative treatment (2:1 ratio). The primary endpoint was the incidence of major adverse events at 9 months, defined as a composite of all-cause death, myocardial infarction, stroke, need for renal artery invasive treatment, or worsening renal function. RESULTS: A total of 17 patients were allocated for renal denervation (n = 11) or conservative treatment (n = 6). Included patients had severe symptomatic heart disease, with markedly depressed left ventricular function (average ejection fraction 26.7 ± 4.9%). For patients randomized to renal denervation, the procedure was performed successfully and uneventfully. After 9 months, the primary endpoint occurred in 36.4% of patients in the renal denervation group and 50.0% in the control arm (p = .6). After 9 months, clinical, laboratory, functional, echocardiographic, and quality of life parameters were similar between groups. CONCLUSIONS: This pilot study suggests that renal denervation is safe and feasible in patients with Chagas cardiomyopathy, warranting future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.

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

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.

Chagas Cardiomyopathy in Latin America Review.

PURPOSE OF REVIEW: Chagas cardiomyopathy is a major public health disease in Latin America and, due to migration, is becoming a worldwide health and economic burden. This review sought to present the clinical and epidemiological aspects of Chagas cardiomyopathy, as well as some specific features and principles of treatment. We also retrospectively assessed our institutional experience with mechanical circulatory support in refractory heart failure due to Chagas cardiomyopathy over a 10-year period. RECENT FINDINGS: The role of antiparasitic treatment in patients with heart failure due to Chagas cardiomyopathy is controversial. Heart transplantation, although formerly contraindicated, is currently established as an important therapeutic option. Also, the favorable characteristics of Chagas patients, such as younger age, little comorbidity, and no reoperations or severe pulmonary hypertension, could be an advantage for a mechanical circulatory support indication in advanced heart failure due to Chagas cardiomyopathy. Despite the absence of large evidence-based data, much has been accomplished since Carlos Chagas' discovery one century ago. Our institutional experience shows that mechanical circulatory support in Chagas patients is associated with more successful bridging to heart transplantation when compared to non-Chagas patients.

An Unusual Suspect in a Case of Left Ventricular Aneurysm.

True left ventricular aneurysms are most frequently seen after acute transmural myocardial infarction. These aneurysms are distinct from apical left ventricular pseudoaneurysms, which can also be seen in ischemia, and have a different treatment course. A major dilemma for clinicians is using echocardiographic information to make this distinction. Coronary angiography aids in this distinction; however, in the case of normal coronaries alternate etiologies must be considered. The differential for a patient with a left ventricular aneurysm and normal coronaries or no prior cardiac surgery is broad and includes traumatic, infectious and infiltrative causes. In this e-challenge, we present an unusual cause of a left ventricular apical aneurysm in a patient with normal coronary arteries residing in the United States.

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.

Cardiac surgery for Chagas disease.

Although Chagas disease is a rare entity in North America, it is associated with significant cardiac morbidity. It is estimated that 20-30% of those who are infected will eventually develop cardiovascular disease secondary to Chagas disease. We review the literature and share our experience on the surgical management of this challenging patient population.

Reactivation of Chagas disease among heart transplant recipients in the United States, 2012-2016.

BACKGROUND: Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non-endemic countries. METHODS: We present our experience with 31 patients with chronic Chagas disease who underwent orthotopic heart transplantation in the United States from 2012 to 2016. Patients were monitored following a standard schedule. RESULTS: Of the 31 patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a majority (95%) were identified by laboratory monitoring using polymerase chain reaction testing. One patient was identified after the onset of clinical symptoms of reactivation. All subjects with evidence of reactivation were alive at follow-up (median: 60 weeks). CONCLUSIONS: Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.

Implantable cardioverter-defibrillator in Chagas heart disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: In patients with Chagas cardiomyopathy (ChCM), sudden cardiac death (SCD) is the leading cause of mortality. Implantable cardioverter-defibrillator (ICD) is a well-established therapy for secondary prevention in patients with structural heart disease, but there are conflicting opinions regarding its efficacy and safety in patients with ChCM. The aim of this meta-analysis was to assess the efficacy of the ICD for secondary prevention in patients with ChCM, comparing mortality as the primary outcome of patients treated with ICD with those treated with amiodarone. METHODS: We systematically searched five databases for studies assessing mortality outcomes in patients with ChCM and sustained ventricular tachycardia (VT) treated with ICD implantation or with amiodarone. The results of studies were pooled using random-effects modeling. RESULTS: There was no randomized clinical trial comparing efficacy of ICD versus medical treatment in patients with ChCM. Six observational studies were included, totalizing 115 patients in amiodarone group and 483 patients in ICD group. The mortality outcome in the ICD population was 9.7 per 100 patient-years of follow-up (95%CI 5.7-13.7) and 9.6 per 100 patient-years in the amiodarone group (95%CI 6.7-12.4) (p = 0.95). Meta-regression did not show any association with LV ejection fraction (p = 0.32), age (p = 0.44), beta-blocker (p = 0.33) or angiotensin-converting enzyme inhibitors (p = 0.096) usage. CONCLUSION: The best available evidence derived from small observational studies suggests that ICD therapy in secondary prevention of sudden death (VT or resuscitated SCD) is not associated with lower rate of all-cause mortality in patients with ChCM. Randomized controlled trials are needed to answer this question.

Challenges of immunosuppressive and antitrypanosomal drug therapy after heart transplantation in patients with chronic Chagas disease: A systematic review of clinical recommendations.

BACKGROUND: Although contraindicated for decades, heart transplantation (HT) has finally become a feasible therapeutic option for the treatment of Chagasic patients with end-stage heart failure. Part of the success in achieving acceptable survival rates after HT is due to the enhancement of the pharmacological management of allograft rejection and reactivation of Trypanosoma cruzi infection. METHODS: By using the framework of a systematic review, we investigated if Chagasic patients who have undergone a HT are treated with similar immunosuppressive and antitrypanosomal regimens in endemic and non-endemic countries and exhibits similar T. cruzi reactivation, allograft rejection and survival rates. From a structured search in PubMed/Medline, Scopus, and Web of Sciences databases, 30 clinical studies were reviewed. RESULTS AND CONCLUSION: Although immunosuppressive regimens are variable in endemic and non-endemic countries, the current evidence supports the administration of lower doses of corticosteroids, adjusted cyclosporine levels (100-150 ng/mL) 3 months after HT, and azathioprine rather than mycophenolate mofetil to reduce the risk of T. cruzi reactivation and rejection episodes. Antitrypanosomal therapy exclusively based on benznidazole, nifurtimox, and allopurinol was consistent in endemic and non-endemic countries, achieving effective results in the control of infection reactivation. The evidence that supports prophylactic antitrypanosomal therapy or administration of allopurinol alone is limited. By highlighting the main sources of research bias, we hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in new research initiatives.