Reverse Potts for the Treatment of Severe Idiopathic Pulmonary Hypertension in Children

ABSTRACT Idiopathic pulmonary arterial hypertension is a rare and progressive disease with poor prognosis. Many patients progressively worsen even when using combinations of specific drugs for its treatment. Herein, we present our experience in the management of three children with severe pulmonary arterial hypertension refractory to clinical treatment who underwent Potts surgery in addition to clinical treatment.

A Curva Volume-Tempo Obtida pela Ecocardiografia Tridimensional na Cardiomiopatia Chagásica: Análise do Mecanismo das Adaptações Hemodinâmicas / The Volume-Time Curve by Three-Dimensional Echocardiography in Chagas Cardiomyopathy: Insights into the Mechanism of Hemodynamic Adaptations

Resumo Fundamento A ecocardiografia tridimensional (ECO 3D) permite a geração de uma curva volume-tempo representativa das alterações no volume ventricular esquerdo (VE) ao longo de todo o ciclo cardíaco. Objetivo O presente estudo tem como objetivo demonstrar as adaptações hemodinâmicas presentes na cardiomiopatia chagásica (CC) por meio das medidas de volume e fluxo obtidas pela curva volume-tempo por ECO 3D. Métodos Vinte pacientes com CC e 15 indivíduos saudáveis foram incluídos prospectivamente em um estudo de desenho transversal. Realizou-se ECO 3D em todos os indivíduos e as curvas volume-tempo do VE foram geradas. O fluxo foi obtido pela primeira derivada da curva volume-tempo por meio do software MATLAB. A significância estatística foi definida com p<0,05. Resultados Embora os pacientes com CC tivessem menor fração de ejeção do VE em comparação com o grupo controle (29,8±7,5 vs. 57,7±6,1, p<0,001), o volume (61,5±25,2 vs. 53,8±21,0, p=0,364) e o fluxo de ejeção máximo durante a sístole (-360,3±147,5 vs. -305,6±126,0, p = 0,231) mostraram-se semelhantes entre os grupos. Da mesma forma, o fluxo máximo na fase de enchimento inicial e durante a contração atrial mostrou-se semelhante entre os grupos. Um aumento na pré-carga expressa pelo volume diastólico final do VE (204,8±79,4 vs. 93,0±32,6), p<0,001) pode manter o fluxo e o volume ejetado semelhantes aos dos controles. Conclusão Com uma ferramenta não invasiva, demonstramos que o aumento no volume diastólico final do VE pode ser o principal mecanismo de adaptação que mantém o fluxo e o volume ejetado no cenário de disfunção sistólica ventricular esquerda severa.

Abstract Background Three-dimensional echocardiography (3D ECHO) allows the generation of a volume-time curve representative of changes in the left ventricular (LV) volume throughout the entire cardiac cycle. Objective This study aims to demonstrate the hemodynamic adaptations present in Chagas cardiomyopathy (CC) by means of the volume and flow measurements obtained by the volume-time curve by 3D ECHO. Methods Twenty patients with CC and 15 healthy subjects were prospectively enrolled in a cross-sectional design study. 3D ECHO was performed in all subjects and the volume over time curves of the LV was generated. The flow was obtained by the first derivative of the volume-time curve using the software MATLAB. Statistical significance was set at p<0.05. Results Although CC patients had lower LV ejection fraction compared to the control group (29.8±7.5 vs. 57.7±6.1, p<0.001), stroke volume (61.5±25.2 vs. 53.8±21.0, p=0.364) and maximum ejection flow during systole (-360.3±147.5 vs. -305.6±126.0, p=0.231) were similar between the groups. Likewise, the maximum flow in the early diastolic filling phase and during atrial contraction was similar between groups. An increase in preload expressed by LV end diastolic volume (204.8±79.4 vs. 93.0±32.6), p<0.001) may maintain the flow and stroke volumes similar to the controls. Conclusion Using a non-invasive tool, we demonstrated that an increase in LV end-diastolic volume may be the main adaptation mechanism that maintains the flow and stroke volumes in the setting of severe LV systolic dysfunction.

Stroke in Chagas disease: from pathophysiology to clinical practice

ABSTRACT Despite substantial progress toward its control, Chagas disease continues to be a major public health problem in Latin America and has become a global health concern. The disease affects approximately 6 million people, of whom 20-40% will develop cardiomyopathy over the years after the initial Trypanosoma cruzi infection. Chagas cardiomyopathy is the most serious and frequent manifestation of Chagas disease. Clinical manifestations vary widely according to the severity of myocardial dysfunction, ranging from asymptomatic to severe forms, including dilated cardiomyopathy with heart failure, arrhythmias, thromboembolism events, and sudden death. Chagas disease is a risk factor for stroke regardless of the severity of cardiomyopathy, which is a leading cause of chronic disability. Classically, stroke etiology in patients with Chagas disease is thought to be cardioembolic and related to apical aneurysm, mural thrombus, and atrial arrhythmias. Although most strokes are thromboembolic, other etiologies have been observed. Small vessel disease, atherosclerosis, and cryptogenic diseases have been reported in patients with Chagas disease and stroke. The potential mechanisms involved in non-embolic strokes include the presence of associated risk factors, pro-inflammatory and prothrombotic disease states, and endothelial dysfunction. However, the contribution of each mechanism to stroke in Chagas disease remains unclear. The review aims to provide an overview of stroke in Chagas disease, highlighting the main pathophysiological mechanisms, clinical presentation, approaches for prevention, and unanswered questions regarding treatment strategies.

Determinantes da capacidade funcional em pacientes com doença de chagas / Determinants of functional capacity in patients with chagas disease

Resumo Fundamento: A doença de Chagas leva à redução da capacidade funcional. Entretanto, o estágio em que o comprometimento funcional é detectável permanece obscuro. Objetivos: O presente estudo teve como objetivo comparar a capacidade funcional de pacientes em diferentes estágios da doença de Chagas e de indivíduos saudáveis e verificar os determinantes do consumo de oxigênio de pico (VO2pico). Métodos: Em um estudo transversal, foram selecionados 160 indivíduos, 35 saudáveis e 125 com doença de Chagas. No grupo chagásico, 61 (49%) estavam na forma indeterminada da doença, 45 (36%) com cardiomiopatia chagásica (CC) e função cardíaca preservada e 19 (15%) com disfunção cardíaca e CC dilatada. Os dados foram analisados por meio de análise de regressão univariada e multivariada. A significância estatística foi fixada em 5%. Resultados: Pacientes na forma indeterminada da doença apresentaram capacidade funcional semelhante a indivíduos saudáveis (p> 0,05). Pacientes com ChC e função cardíaca preservada apresentaram VO2pico menor que os pacientes na forma indeterminada (p <0,05), mas apresentaram valores de VO2pico semelhantes ao ChC dilatado (p = 0,46). A idade, sexo masculino, classe funcional da NYHA, pressão arterial diastólica, razão entre a velocidade do fluxo transmitral diastólico precoce e a velocidade anular mitral diastólica precoce, a fração de ejeção do ventrículo esquerdo (FEVE) e o diâmetro diastólico final do ventrículo esquerdo foram associados à capacidade funcional. Porém, apenas idade, sexo masculino, FEVE e classe funcional da NYHA permaneceram associados ao VO2pico no modelo final (R2 ajustado = 0,60). Conclusão: Pacientes com CC apresentam menor capacidade funcional do que pacientes na forma indeterminada. FEVE, idade, sexo masculino e classe funcional da NYHA foram determinantes do VO2pico em pacientes com doença de Chagas.

Abstract Background: Chagas disease leads to reduced functional capacity. However, the stage at which functional impairment is detectable remains unclear. Objectives: The present study was addressed to compare the functional capacity of patients at different stages of Chagas disease and healthy individuals and to verify the determinants of peak oxygen uptake (VO2peak). Methods: In a cross-sectional study, 160 individuals were selected, 35 healthy and 125 with Chagas disease. In the Chagasic group, 61 (49%) were in the indeterminate form of the disease, 45 (36%) with Chagas cardiomyopathy (ChC) and preserved cardiac function and 19 (15%) with cardiac dysfunction and dilated ChC. The data were analyzed using univariate and multivariate regression analysis. Statistical significance was set at 5%. Results: Patients in the indeterminate form of disease showed similar functional capacity to healthy individuals (p>0.05). Patients with ChC and preserved cardiac function had lower VO2peak than patients in the indeterminate form (p<0.05), but showed similar VO2peak values than dilated ChC (p=0.46). The age, male sex, NYHA functional class, diastolic blood pressure, ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter were associated with functional capacity. However, only age, male sex, LVEF and NYHA functional class, remained associated with VO2peak in the final model (adjusted R2=0.60). Conclusion: Patients with ChC had lower functional capacity than patients in the indeterminate form. LVEF, age, male sex and NYHA functional class were determinants with VO2peak in patients with Chagas disease.

Bedside echocardiography to predict mortality of COVID-19 patients beyond clinical data: Data from the PROVAR-COVID study

Abstract INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, being more frequent in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside echocardiography (echo), in patients hospitalized with COVID-19. METHODS: Patients admitted in 2 reference hospitals in Brazil from Jul to Sept/2020 with confirmed COVID-19 and moderate/severe presentations underwent clinical and laboratory evaluation, and focused bedside echo (GE Vivid-IQ), at the earliest convenience, with remote interpretation. The association between demographics, clinical comorbidities and echo variables with all-cause hospital mortality was assessed, and factors significant at p<0.10 were put into multivariable models. RESULTS: Total 163 patients were enrolled, 59% were men, mean age 64±16 years, and 107 (66%) were admitted to intensive care. Comorbidities were present in 144 (88%) patients: hypertension 115 (71%), diabetes 61 (37%) and heart failure 22 (14%). In-hospital mortality was 34% (N=56). In univariate analysis, echo variables significantly associated with death were: LV ejection fraction (LVEF, OR=0.94), RV fractional area change (OR=0.96), tricuspid annular plane systolic excursion (TAPSE, OR=0.83) and RV dysfunction (OR=5.3). In multivariate analysis, after adjustment for clinical and demographic variables, independent predictors of mortality were age≥63 years (OR=5.53, 95%CI 1.52-20.17), LVEF<64% (OR=7.37, 95%CI 2.10-25.94) and TAPSE<18.5 mm (OR=9.43, 95% CI 2.57-35.03), and the final model had good discrimination, with C-statistic=0.83 (95%CI 0.75-0.91). CONCLUSION: Markers of RV and LV dysfunction assessed by bedside echo are independent predictors of mortality in hospitalized COVID-19 patients, after adjustment for clinical variables.

Exercise tests in Chagas cardiomyopathy: an overview of functional evaluation, prognostic significance, and current challenges

Abstract Patients with Chagas cardiomyopathy (ChC) usually progress with fatigue and dyspnea. Exercise tests are valuable for the functional evaluation of these patients. However, information about the applicability of the exercise tests is scattered, and no studies have systematically reviewed the results. Thus, the present review explored the general aspects and prognostic value of exercise tests in patients with ChC. A literature search of the MEDLINE, Web of Science, CINAHL, Scopus, and LILACS databases was performed to identify relevant studies. There were no data restrictions, and articles that met the objective of the study were selected. Articles written in English, Portuguese, and Spanish were considered, and 25 articles were finally included. The peak oxygen uptake (VO2peak) was correlated with demographic and echocardiographic variables. Echocardiographic features of the left ventricular diastolic function and right ventricular systolic function appeared to be determinants of functional capacity, in addition to age and sex. VO2peak was associated with higher mortality, especially in patients with dilated ChC. The minute ventilation/carbon dioxide production slope (VE/VCO2 slope) was a strong predictor of survival; however, more studies are needed to verify this observation. Field tests showed moderate to strong correlation with VO2peak and thus may be inexpensive tools for the functional evaluation of patients with ChC. However, few studies have verified their prognostic significance. While exercise tests are useful tools for functional assessment, information is scarce regarding further considerations, and many of the criteria are based on guidelines for other heart diseases.

Valor do ecocardiograma na Endocardite Infecciosa associada aos dispositivos cardíacos implantáveis / Use of echocardiography in Infectious Endocarditis associated with implantable cardiac devices

Nas últimas décadas, o aumento das indicações para dispositivos cardíacos eletrônicos implantáveis tem sido acompanhado pela elevação dos casos de complicações relacionadas ao seu uso, dentre elas a endocardite infecciosa. Apesar dos avanços diagnósticos e terapêuticos da doença, esta mantém elevada morbimortalidade. Os casos relacionados aos dispositivos apresentam importantes limitações referentes aos critérios e aos métodos diagnósticos que implicam na tomada de decisão terapêutica sobre retirada do dispositivo, com risco de morte e outras complicações. Ainda assim, o ecocardiograma mantém um grande valor no diagnóstico da endocardite infecciosa relacionada a dispositivos cardíacos e de suas complicações. O entendimento das limitações e dos desafios acerca do diagnóstico reforça a necessidade de mais estudos sobre do tema. O presente artigo visa descrever a epidemiologia, a microbiologia, os fatores de risco, a patogenia, o diagnóstico e o tratamento da endocardite infecciosa associada aos dispositivos cardíacos eletrônicos implantáveis, visando demonstrar, principalmente, o valor dos exames de imagem na abordagem dessa condição clínica, com ênfase nos achados ao ecocardiograma.

In recent decades, the increase in indications for implantable electronic cardiac devices has been accompanied by an increase in cases of complications related to their use, including infectious endocarditis. Despite the diagnostic and therapeutic advances of the disease, it maintains high morbidity and mortality. The cases related to the devices have important limitations regarding the criteria and diagnostic methods that imply in making a therapeutic decision about removing the device, with risk of death and other complications. Still, echocardiography remains of great value in the diagnosis of infective endocarditis related to cardiac devices and their complications. Understanding the limitations and challenges regarding diagnosis reinforces the need for further studies on the topic. This article aims to describe the epidemiology, microbiology, risk factors, pathogenesis, diagnosis and treatment of infective endocarditis associated with implantable electronic cardiac devices, aiming to demonstrate, mainly, the value of imaging tests in addressing this clinical condition , with emphasis on echocardiogram findings.

Rheumatic heart disease in the modern era: recent developments and current challenges

Abstract Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease.

Reduced functional capacity in patients with Chagas disease: a systematic review with meta-analysis

Abstract Reduced peak oxygen uptake (VO2peak) is a common clinical finding in progressive Chagas disease. However, the disease stage in which functional impairment is detectable remains uncertain. The present study compared functional capacity between healthy controls and patients with different clinical forms of Chagas disease. A systematic review and meta-analysis (PROSPERO database CRD42017058353) was conducted following a search of the MEDLINE, Web of Science, CINAHL, and LILACS databases from September to December 2017 for articles published in English, Spanish, or Portuguese, with no date restrictions. We included studies that compared the VO2peak between healthy and Chagas disease patients, stratified according to 3 clinical forms [no apparent cardiac disease, non-dilated Chagas heart disease (CHD), and dilated CHD]. Seven cross-sectional studies were included. Chagas disease patients without apparent cardiac disease (n=208) had VO2peak values [mean difference, -1.55ml/kg/min; 95% confidence interval (CI), -4.98ml/kg/min to 1.88ml/kg/min] similar to those of healthy controls (n=105; p=0.38, I2=52%). In non-dilated CHD (n=159), VO2peak was 8.71ml/kg/min lower (95% CI, -13.99 to -3.42ml/kg/min) than in healthy controls (n=59; p=0.001, I2=75%). VO2peak was also significantly lower (mean difference, -9.30ml/kg/min; 95% CI, -11.34 to -7.25ml/kg/min) in dilated CHD patients (n=131) than in healthy controls (n=53; p<0.001, I2=0%). Exercise capacity in Chagas disease patients without apparent cardiac disease is similar to that in healthy controls. Functional impairment in Chagas disease is detectable in the early stages of cardiac involvement, even in the absence of systolic dysfunction and signs of heart failure.

Prognostic value of serum brain-derived neurotrophic factor levels in patients with Chagas cardiomyopathy

BACKGROUND Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. METHODS Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. RESULTS After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026). CONCLUSION In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease. .

Health-related quality of life in patients with Chagas disease: a review of the evidence

Chagas disease (ChD), a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL) impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH) for searches in PubMed and the Scientific Electronic Library Online (SciELO), 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1) cardiac involvement is associated with a worse HRQoL in ChD patients; 2) HRQoL is associated with the patients' functional capacity; and 3) simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

Echocardiographic parameters associated with pulmonary congestion in Chagas cardiomyopathy / Parâmetros ecocardiográficos associados com a congestão pulmonar na miocardiopatia chagásica

INTRODUCTION: Discrepancy between the intensity of pulmonary congestion and the grade of cardiomegaly seems to be a common finding of Chagas cardiomyopathy, in spite of significant systolic dysfunction of the left ventricle. Its mechanism has not been established. The aim of this study was to investigate pulmonary congestion and to analyze if it correlated with Doppler echocardiographic parameters in patients with Chagas dilated cardiomyopathy. METHODS: Fifty-five patients with positive serology tests for Trypanosoma cruzi and Chagas dilated cardiomyopathy were studied. Chest x-rays, Doppler echocardiogram and plasmatic brain natriuretic peptide levels were obtained in all patients. The degree of pulmonary venous vessels changes on chest x-ray was graded using a pulmonary congestion score, and then compared to Doppler echocardiographic parameters. RESULTS: Mean age was 48.5 ± 11.2 years and 29 percent were women. The majority (95 percent) of patients were in NYHA functional class I and II. Mild pulmonary congestion by chest x-ray was found in 80 percent of the patients. In a multivariate analysis, left ventricular ejection fraction, right ventricular TEI index and the color M-mode velocity correlated with the degree of pulmonary congestion. CONCLUSIONS: Pulmonary venous changes on chest x-rays are frequent, but usually mild in patients with Chagas dilated cardiomyopathy. The degree of pulmonary congestion correlates with Doppler echocardiographic left and right ventricular dysfunction and with color M-mode velocity.

INTRODUÇÃO: Na miocardiopatia chagásica, é considerado haver uma menor intensidade de congestão pulmonar, mesmo na vigência de disfunção ventricular esquerda importante, não havendo ainda explicação definitiva para este fenômeno. O objetivo deste estudo foi de investigar a presença de congestão pulmonar na miocardiopatia chagásica e analisar se a intensidade da congestão esteve associada com parâmetros morfofuncionais ecocardiográficos de disfunção cardíaca. MÉTODOS: Cinquenta e cinco pacientes com sorologia positiva para o Trypanosoma cruzi e portadores de miocardiopatia chagásica foram estudados. Todos os pacientes foram submetidos ao estudo radiológico do tórax, ecocardiograma e dosagem plasmática do peptídeo natriurético cerebral. O grau de congestão pulmonar foi quantificado através de um escore da congestão pulmonar, e então comparado com os parâmetros ecocardiográficos. RESULTADOS: A idade média foi de 48.5 ± 1.2 anos e 29 por cento eram mulheres. A maior (95 por cento) parte dos pacientes encontrava-se na classe funcional I e II. Discreta congestão pulmonar à radiografia do tórax foi encontrada em 80 por cento dos pacientes. Na análise multivariada, a fração de ejeção do ventrículo esquerdo, o índice de TEI do ventrículo direito e a velocidade ao color M mode foram as variáveis que mais estiveram associadas com o grau de congestão pulmonar. CONCLUSÕES: Nos pacientes com miocardiopatia chagásica, as alterações do fluxo venoso pulmonar foram frequentes, porém discretas. O grau de congestão pulmonar associou com parâmetros ecocardiográficos de disfunção ventricular esquerda e direita e com a velocidade do color M mode.