Rapidly progressive respiratory failure after helminth larvae ingestion.

BACKGROUND: Self-administration of helminths has gained attention among patients as a potential but unproven therapy for autoimmune disease. We present a case of rapidly progressive respiratory failure in a patient with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) as a result of self-administration of parasitic organisms. CASE: A 45-year-old woman with a history of interstitial lung disease and PAH due to limited cutaneous SSc presented to pulmonary clinic with worsening dyspnea, cough, and new onset hypoxemia. Three months prior to presentation she started oral helminth therapy with Necator americanus as an alternative treatment for SSc. Laboratory evaluation revelaed eosinophilia and elevated IgE levels. IgG antibodies to Strongyloides were detected. High resolution computed tomography of the chest revealed progressive ILD and new diffuse ground glass opacities. Transthoracic echocardiogram and right heart catheterization illustrated worsening PAH and right heart failure. The patient was admitted to the hospital and emergently evaluated for lung transplantation but was not a candidate for transplantation due to comorbidities. Despite aggressive treatment for PAH and right heart failure, her respiratory status deteriorated, and the patient transitioned to comfort-focused care. CONCLUSION: Although ingestion of helminths poses a risk of infection, helminth therapy has been investigated as a potential treatment for autoimmune diseases. In this case, self-prescribed helminth ingestion precipitated fatal acute worsening of lung inflammation, hypoxemia, and right heart dysfunction, highlighting the risk of experimental helminth therapy in patients, especially those with underlying respiratory disease.

Measurement of multiple cytokines for discrimination and risk stratification in patients with Chagas' disease and idiopathic dilated cardiomyopathy.

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.

Chagas disease is associated with a poor outcome at 1-year follow-up after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapeutic modality for patients with heart failure (HF). The effectiveness of this treatment for event reduction is based on clinical trials where the population of patients with Chagas' disease (DC) is underrepresented. OBJECTIVE: To evaluate the prognosis after CRT of a population in which CD is an endemic cause of HF. METHODS: A retrospective cohort conducted between January 2015 and December 2016 that included patients with HF and left ventricular ejection fraction (LVEF) of less than 35% and undergoing CRT. Clinical and demographic data were collected to search for predictors for the combined outcome of death or hospitalization for HF at one year after CRT implantation. RESULTS: Fifty-four patients were evaluated, and 13 (24.1%) presented CD as the etiology of HF. The mean LVEF was 26.2± 6.1%, and 36 (66.7%) patients presented functional class III or IV HF. After the mean follow-up of 15 (±6,9) months, 17 (32.1%) patients presented the combined outcome. In the univariate analysis, CD was associated with the combined event when compared to other etiologies of HF, 8 (47%) vs. 9 (13,5%), RR: 3,91 CI: 1,46-10,45, p=0,007, as well as lower values of LVEF. In the multivariate analysis, CD and LVEF remained independent risk factors for the combined outcome. CONCLUSION: In a population of HF patients undergoing CRT, CD was independently associated with mortality and hospitalization for HF.

Chagas disease is associated with a poor outcome at 1-year follow-up after cardiac resynchronization therapy

SUMMARY BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapeutic modality for patients with heart failure (HF). The effectiveness of this treatment for event reduction is based on clinical trials where the population of patients with Chagas' disease (DC) is underrepresented. OBJECTIVE: To evaluate the prognosis after CRT of a population in which CD is an endemic cause of HF. METHODS: A retrospective cohort conducted between January 2015 and December 2016 that included patients with HF and left ventricular ejection fraction (LVEF) of less than 35% and undergoing CRT. Clinical and demographic data were collected to search for predictors for the combined outcome of death or hospitalization for HF at one year after CRT implantation. RESULTS: Fifty-four patients were evaluated, and 13 (24.1%) presented CD as the etiology of HF. The mean LVEF was 26.2± 6.1%, and 36 (66.7%) patients presented functional class III or IV HF. After the mean follow-up of 15 (±6,9) months, 17 (32.1%) patients presented the combined outcome. In the univariate analysis, CD was associated with the combined event when compared to other etiologies of HF, 8 (47%) vs. 9 (13,5%), RR: 3,91 CI: 1,46-10,45, p=0,007, as well as lower values of LVEF. In the multivariate analysis, CD and LVEF remained independent risk factors for the combined outcome. CONCLUSION: In a population of HF patients undergoing CRT, CD was independently associated with mortality and hospitalization for HF.

RESUMO INTRODUÇÃO: A terapia de ressincronização cardíaca (TRC) é uma modalidade terapêutica para pacientes com insuficiência cardíaca (IC). A eficácia desse tratamento para redução de eventos baseia-se em ensaios clínicos em que a população de pacientes com doença de Chagas (DC) é sub-representada. OBJETIVO: Avaliar o prognóstico após TRC em uma população em que a DC é uma causa frequente de IC. MÉTODOS: Coorte retrospectiva realizada entre janeiro de 2015 e dezembro de 2016, sendo incluídos pacientes portadores de IC com fração de ejeção do ventrículo esquerdo (Feve) menor que 35% e submetidos à TRC. Os dados clínicos e demográficos foram coletados para pesquisa de preditores para o desfecho combinado de morte ou internação por IC após implante da TRC. RESULTADOS: Foram avaliados 54 pacientes, dos quais 13 (24,1%) apresentavam a DC como etiologia da IC. A Feve média foi de 26,2% (±6,1) e 36 (66,7%) pacientes apresentavam classe funcional de IC III ou IV. Após o seguimento médio de 15 meses, 17 (32,1%) pacientes apresentaram o desfecho combinado. Na análise univariada, a DC esteve associada ao evento combinado quando comparada a outras etiologias de IC, 8 (47%) vs 9 (13,5%), RR: 3,91 IC: 1,46-10,45, p=0,007, assim como valores mais baixos da Feve. Na análise multivariada, a DC e a Feve permaneceram como fatores de risco independentes para o desfecho combinado. CONCLUSÃO: Em uma população de pacientes com IC submetidos à TRC, a doença de Chagas esteve independentemente associada à mortalidade e internação por insuficiência cardíaca no seguimento de 15 meses.

Cardiac involvement in trypanosomiasis in sheep experimentally infected by Trypanosoma vivax (Ziemman, 1905).

The objective of the present study was to evaluate the clinical signs, electrocardiographic signs and evolution of histopathological lesions in the heart of sheep experimentally infected by Trypanosoma vivax during the acute and chronic phases of infection as well as to investigate the presence of parasitic DNA in the heart using polymerase chain reaction (PCR). Twenty-two male sheep were divided into the following four groups: G1, which consisted of six sheep infected by T. vivax that were evaluated until 20 days post-infection (dpi; acute phase); G2, which consisted of six sheep infected by T. vivax that were evaluated until 90 dpi (chronic phase); and G3 and G4 groups, which each consisted of five uninfected sheep. At the end of the experimental period, electrocardiographic evaluations and necroscopic examinations were performed. Fragments of the heart were collected and stained by Hematoxylin-Eosin and Masson's trichrome, and the fragments were also evaluated by PCR for T. vivax. G2 animals presented clinical signs suggestive of heart failure and electrocardiogram alterations characterized by prolonged P, T and QRS complex durations as well as by a cardiac electrical axis shift to the left and increased heart rate. In these animals, mononuclear multifocal myocarditis and interstitial fibrosis were also observed. PCR revealed positivity for T. vivax in two G1 animals and in all G2 animals. Thus, these findings suggested that T. vivax is responsible for the occurrence of cardiac lesions, which are related to heart failure, electrocardiographic alterations and mortality of the infected animals.

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.

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.

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.

Reassessment of quality of life domains in patients with compensated Chagas heart failure after participating in a cardiac rehabilitation program.

INTRODUCTION:: We evaluated the effects of a cardiac rehabilitation program on quality of life. METHODS: This secondary analysis of a single-arm study included 12 patients with Chagas heart failure. The cardiac rehabilitation program comprised exercise training and nutritional and pharmaceutical counseling. Quality of life was assessed using the SF-36 questionnaire. RESULTS:: The program promoted improved physical functioning (ß= +5.7; p=0.003), role-physical (ß= +1.9; p=0.03), and bodily pain (ß= +3.5; p=0.02) scores. Moreover, the summary physical health score (ß= +1.4; p=0.001) improved. CONCLUSION:: The cardiac rehabilitation program significantly improved the physical quality of life of patients with Chagas heart failure.

Reassessment of quality of life domains in patients with compensated Chagas heart failure after participating in a cardiac rehabilitation program

Abstract INTRODUCTION: We evaluated the effects of a cardiac rehabilitation program on quality of life. METHODS This secondary analysis of a single-arm study included 12 patients with Chagas heart failure. The cardiac rehabilitation program comprised exercise training and nutritional and pharmaceutical counseling. Quality of life was assessed using the SF-36 questionnaire. RESULTS: The program promoted improved physical functioning (β= +5.7; p=0.003), role-physical (β= +1.9; p=0.03), and bodily pain (β= +3.5; p=0.02) scores. Moreover, the summary physical health score (β= +1.4; p=0.001) improved. CONCLUSION: The cardiac rehabilitation program significantly improved the physical quality of life of patients with Chagas heart failure.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study.

INTRODUCTION: The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS: A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS: Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS: CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.

Cardiac rehabilitation program in patients with Chagas heart failure: a single-arm pilot study

Abstract: INTRODUCTION: The benefit of a cardiac rehabilitation (CR) program for patients with Chagas heart failure (CHF) remains unclear. Therefore, we aimed to investigate the effects of CR for CHF patients. METHODS: A single-arm pilot study, including 12 patients with CHF, was performed. Patients participated in an 8-month physical exercise intervention, comprising aerobic, strength, and stretching exercises (3 times per week, 60 minutes per session). Nutritional and pharmaceutical counseling were also performed. Functional capacity (cardiopulmonary exercise test), muscle respiratory strength (manovacuometry), and body composition (anthropometry and skinfolds) were evaluated at baseline, and after 4 and 8 months of intervention. Cardiac function (echocardiography), biomarkers (lipid profile, glucose, and glycated hemoglobin) and quality of life (Minnesota Living with Heart Failure Questionnaire) were assessed at baseline and at the end of the intervention. RESULTS: Seven of 12 patients included in the study completed the 8-month follow-up period. Only 2 moderate adverse events occurred during the exercise training. Functional capacity improved after 4 months of CR, while left ventricular ejection fraction (LVEF) and respiratory strength improved after 8 months. Patients with right ventricular (RV) dysfunction at baseline exhibited an improvement in functional capacity after 4 months, and improvements in left ventricular (LV) diastolic pressure, respiratory strength, and quality of life at the end of follow-up. Conversely, those with normal baseline RV function demonstrated LVEF increases that were not observed in patients with RV dysfunction. CONCLUSIONS: CR was feasible, safe, and has important clinical benefits for patients with CHF, specifically for cardiac function and muscle respiratory strength.

Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis.

AIMS: Invaginations of the cellular membrane called t-tubules are essential for maintaining efficient excitation-contraction coupling in ventricular cardiomyocytes. Disruption of t-tubule structure during heart failure has been linked to dyssynchronous, slowed Ca(2+) release and reduced power of the heartbeat. The underlying mechanism is, however, unknown. We presently investigated whether elevated ventricular wall stress triggers remodelling of t-tubule structure and function. METHODS AND RESULTS: MRI and blood pressure measurements were employed to examine regional wall stress across the left ventricle of sham-operated and failing, post-infarction rat hearts. In failing hearts, elevated left ventricular diastolic pressure and ventricular dilation resulted in markedly increased wall stress, particularly in the thin-walled region proximal to the infarct. High wall stress in this proximal zone was associated with reduced expression of the dyadic anchor junctophilin-2 and disrupted cardiomyocyte t-tubular structure. Indeed, local wall stress measurements predicted t-tubule density across sham and failing hearts. Elevated wall stress and disrupted cardiomyocyte structure in the proximal zone were also associated with desynchronized Ca(2+) release in cardiomyocytes and markedly reduced local contractility in vivo. A causative role of wall stress in promoting t-tubule remodelling was established by applying stretch to papillary muscles ex vivo under culture conditions. Loads comparable to wall stress levels observed in vivo in the proximal zone reduced expression of junctophilin-2 and promoted t-tubule loss. CONCLUSION: Elevated wall stress reduces junctophilin-2 expression and disrupts t-tubule integrity, Ca(2+) release, and contractile function. These findings provide new insight into the role of wall stress in promoting heart failure progression.

Toxoplasma gondii Serology and Outcomes After Heart Transplantation: Contention in the Literature.

BACKGROUND: Toxoplasma gondii is an endemic pathogen to which approximately half of healthy patients develop antibodies. Toxoplasma serology is routinely assessed prior to heart transplantation. It has been suggested that donor or recipient toxoplasma serologic status may be associated with poor long-term outcomes post-transplantation, but current literature reveals conflicting results. METHODS: From 1995 to 2012 at our single center, we retrospectively reviewed 785 heart transplant patients for pre-transplantation T. gondii serology. Patients were divided into T. gondii seronegative and seropositive groups. Subgroups in each group were created based on whether the donor was seropositive or seronegative. We assessed survival, freedom from nonfatal major adverse cardiac events, and freedom from cardiac allograft vasculopathy at 5 years post-transplantation. RESULTS: No significant difference was found between 5-year outcomes of pre-transplant T. gondii seronegative and T. gondii seropositive recipients post-heart transplantation. However, in the donor-seropositive/recipient-seronegative subgroup (D+/R-), there was a significantly lower 5-year survival rate compared to the cohort of donor-seronegative/recipient-seronegative (D-/R-) patients (60% vs 87%, P = .04). After adjustment by multivariate analysis, D+/R- status conferred a trend towards increased mortality (HR 3.0, P = .06). CONCLUSIONS: Toxoplasma serology prior to heart transplantation does not appear to impact post-transplantation outcome. However, toxoplasma seronegative patients who receive toxoplasma seropositive hearts appear to have poorer 5-year survival compared to toxoplasma seronegative patients who received toxoplasma seronegative hearts. Due to the small sample size, the association between T. gondii serology mismatch and long-term survival warrants further study.

Telecare for diabetes, CHF or COPD: effect on quality of life, hospital use and costs. A randomised controlled trial and qualitative evaluation.

OBJECTIVES: To assess the effect of telecare on health related quality of life, self-care, hospital use, costs and the experiences of patients, informal carers and health care professionals. METHODS: Patients were randomly assigned either to usual care or to additionally entering their data into a commercially-available electronic device that uploaded data once a day to a nurse-led monitoring station. Patients had congestive heart failure (Site A), chronic obstructive pulmonary disease (Site B), or any long-term condition, mostly diabetes (Site C). Site C contributed only intervention patients - they considered a usual care option to be unethical. The study took place in New Zealand between September 2010 and February 2012, and lasted 3 to 6 months for each patient. The primary outcome was health-related quality of life (SF36). Data on experiences were collected by individual and group interviews and by questionnaire. RESULTS: There were 171 patients (98 intervention, 73 control). Quality of life, self-efficacy and disease-specific measures did not change significantly, while anxiety and depression both decreased significantly with the intervention. Hospital admissions, days in hospital, emergency department visits, outpatient visits and costs did not differ significantly between the groups. Patients at all sites were universally positive. Many felt safer and more cared-for, and said that they and their family had learned more about managing their condition. Staff could all see potential benefits of telecare, and, after some initial technical problems, many staff felt that telecare enabled them to effectively monitor more patients. CONCLUSIONS: Strongly positive patient and staff experiences and attitudes complement and contrast with small or non-significant quantitative changes. Telecare led to patients and families taking a more active role in self-management. It is likely that subgroups of patients benefitted in ways that were not measured or visible within the quantitative data, especially feelings of safety and being cared-for. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000269033.

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.