As the global COVID-19 pandemic advances, it increasingly impacts the vulnerable populations who already bear a heavy burden of neglected tropical diseases. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19’s potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs.

Abstract INTRODUCTION: Benznidazole (BZL) and Nifurtimox (NFX) are the pharmacological treatment for acute phase Chagas Disease (CD); however, therapy resistance and residual mortality development remain important unresolved issues. Posaconazole (POS) has shown a trypanocidal effect in vivo and in vitro. Thus, this study aimed at comparing the T. Cruzi parasitic load-reducing effect of the combination of BZL+POS against that of monotherapy with either, during acute phase CD, in an experimental murine model. METHODS Nineteen Wistar rats were randomly allocated to four groups and inoculated with the trypomastigotes of T. cruzi strain´s JChVcl1. The rats were administered anti-parasites from day 20-29 post-infection. The Pizzi and Brener method was used for parasitemia measurement. Longitudinal data analysis for the continuous outcome of repeated measures was performed using parasitemia as the outcome measured at days 20, 22, 24, 27, and 29 post-infection. RESULTS All four groups had similar parasitic loads (p=0.143) prior to therapy initiation. Among the three treatment groups, the BZL+POS (n=5) group showed the highest mean parasitic load reduction (p=0.000) compared with the control group. Likewise, the BZL+POS group rats showed an earlier therapeutic effect and were the only ones without parasites in their myocardial samples. CONCLUSIONS: Treatment of acute phase CD with BZL+POS was more efficacious at parasitemia and myocardial injury reduction, compared with monotherapy with either.

Abstract Distraction osteogenesis (DO) relies on the recruitment and proliferation of mesenchymal stem cells (MSC) to the target site, where they differentiate into osteoblasts to promote bone formation. Nevertheless, MSC recruitment appears to be slow and limits bone formation in DO defects. Thus, this systematic review aims to evaluate the ability of locally applied MSC to enhance bone formation in DO preclinical models. Databases were searched for quantitative pre-clinical controlled studies that evaluated the effect of local administration of MSC on DO bone formation. Eligible studies were identified and data regarding study characteristics, outcome measures and quality were extracted. Nine studies met the inclusion criteria. Autogenous and xenogenous MSC were used to promote DO bone formation. These included bone marrow-derived MSC, adipose tissue-derived MSC and MSC derived from human exfoliated deciduous teeth. Meta-analysis was not possible due to heterogeneities in study designs. Local MSC implantation was not associated with adverse effects. In 4 out of the 5 studies, locally delivered undifferentiated bone-marrow MSC had a positive effect on DO bone formation. Few studies evaluated the therapeutic effects of MSC from other sources. The adjunct use of biologically active molecules or forced expression of key genes involved in osteogenesis further boosted the ability of bone-marrow MSC to promote DO bone formation. While risk of bias and heterogeneity limited the strength of this systematic review, our results suggest that the use of MSC is safe and may provide beneficial effects on DO bone formation.

Background: Atrial fibrillation (AF) produces a five-fold increase in the risk of stroke, and the exclusion of the left atrial appendage (LAA), the main source of thrombi, is an interesting therapeutic option in patients with contraindication for oral anticoagulation. Objectives: The goal of this study was to evaluate the initial experience, immediate results and outcome at 45 days of percutaneous closure of the LAA in patients with AF and high risk of thromboembolic events, in whom chronic oral anticoagulation was contrain-dicated. Methods: Twenty-two patients with non-valvular AF and a CHA2DS2-Vasc ≥2 in whom there was contraindication or impossibility of long-term oral anticoagulation underwent percutaneous closure of the LAA with the WATCHMANT device. The patients were evaluated 45 days after the procedure by clinical assessment and transesophageal echocardiography. Results: The implant was successful in 21 of 22 patients (95.4%). Median (interquartile range) age and CHA2DS2-VASc and HAS-BLED scores were 76 years (IQR 14.5), 5 (IQR 1.5) and 4 (IQR 1), respectively. Three (13.6%) periprocedural complications were observed: one cardiac tamponade requiring surgery, one concealed major bleeding and one pseudoaneurysm of the femoral artery. No device-related complications or thromboembolic events were observed during the 45-day follow-up. The LAA was adequately excluded in 95% of the cases. Conclusions: In our initial experience, the procedure is feasible, with an acceptable risk, and can be considered a therapeutic option in patients with AF and high thromboembolic risk who cannot receive oral anticoagulation.

Introducción: La fibrilación auricular (FA) incrementa cinco veces el riesgo de accidente cerebrovascular y la orejuela auricular izquierda (OI) es la principal fuente de formación de trombos, por lo que su exclusión se presenta como una alternativa terapéutica interesante en pacientes con contraindicación para la anticoagulación oral. Objetivos: Evaluar la experiencia inicial, los resultados del implante y la evolución a los 45 días del cierre percutáneo de la OI en pacientes con FA de riesgo tromboembólico alto en los cuales no podía emplearse la anticoagulación oral crónica. Material y métodos: Veintidós pacientes con FA no valvular y CHA2DS2-Vasc ≥2 en los que la anticoagulación a largo plazo estaba contraindicada o era impracticable fueron sometidos al cierre percutáneo de la OI con el dispositivo WATCHMAN®. Los pacientes fueron evaluados a los 45 días mediante control clínico y con ecocardiografía transesofágica. Resultados: El implante fue exitoso en 21 de los 22 pacientes (95,4%). Las medianas (rango intercuartil) de edad, CHA2DS2-VASc y HAS-BLED fueron 76 años (RIC 14,5), 5 (RIC 1,5) y 4 (RIC 1), respectivamente. Se observaron 3 (13,6%) complicaciones periprocedimiento: un taponamiento que requirió revisión quirúrgica, un sangrado mayor oculto y un seudoaneurisma femoral. Durante el seguimiento a 45 días no se observaron complicaciones relacionadas con el dispositivo ni eventos tromboembólicos. En el 95% de los casos, la OI se encontraba adecuadamente excluida. Conclusiones: En nuestra experiencia inicial, el procedimiento es factible con un riesgo aceptable, constituyéndose en una alternativa terapéutica en pacientes con FA de riesgo tromboembólico alto que no pueden recibir anticoagulantes orales.

OBJETIVO: A doença de Chagas constitui importante problema de saúde pública global devido às mudanças nos padrões migratórios. O estudo eletrofisiológico é usualmente indicado na avaliação da função do nó sinusal, condução pelo nó atrioventricular e sistema His-Purkinje e mecanismos das arritmias. O objetivo deste estudo foi descrever as características do estudo eletrofisiológico em pacientes com doença de Chagas. MÉTODOS: Estudo retrospectivo e descritivo de 115 pacientes consecutivos com doença de Chagas submetidos ao estudo eletrofisiológico nos últimos 3 anos em centro terciário no Brasil. Características basais, eletrocardiográficas, ecocardiográficas e de Holter de 24 horas foram avaliadas e correlacionadas aos achados do estudo eletrofisiológico. RESULTADOS: Os tempos corrigidos de recuperação do nó sinusal e condução sinoatrial foram anormais em 6,9% e 26,1% dos pacientes, respectivamente. Apresentaram condução atrioventricular anormal 37 (32,2%) pacientes. A condução intraventricular mostrou-se alterada em 39 (33,9%) pacientes. Em aproximadamente 48%, houve indução de arritmias ventriculares sustentadas, sendo a maioria monomórfica (83,6%). A morfologia de bloqueio de ramo direito foi a mais comumente observada (52,7%). Dentre as arritmias, 51% associaram-se a sintomas/instabilidade hemodinâmica, 60% necessitaram de cardioversão elétrica e 27,3% de estimulação rápida. O sítio de origem mais comum foi a parede inferosseptal do ventrículo esquerdo (18,2%), seguido pela parede posterobasal (11%). Pacientes com fração de ejeção<40% tiveram risco 1,94 vez maior de indução de arritmias ventriculares comparados àqueles com fração de ejeção>60% (OR: 1,94; IC95%: 1,12-3,38; p=0,01). A presença de arritmias ventriculares complexas no Holter não foi preditiva de indução de arritmias ventriculares. CONCLUSÕES: Chagásicos com fração de ejeção baixa apresentam maior risco de arritmias ventriculares induzidas. Disfunção do nó sinusal e anormalidades da condução atrioventricular e do sistema His-Purkinje ocorrem em aproximadamente um terço dos pacientes. Arritmias ventriculares complexas no Holter não foram preditoras de indução de arritmias ventriculares nessa amostra populacional.

OBJECTIVE: Chagas disease has become a global problem due to changing migration patterns. An electrophysiological study is generally indicated for assessing sinus node function, conduction through the atrioventricular node and His-Purkinje system, in addition to evaluating the mechanisms of arrhythmia. The aim of this study was to describe the characteristics of electrophysiological study findings in patients with Chagas disease. METHODS: A retrospective descriptive study of 115 consecutive patients with Chagas disease undergoing an electrophysiological study over the last three years in a tertiary hospital in Brazil. Baseline characteristics, electrocardiogram, echocardiogram, and 24-hour Holter monitoring findings were recorded and correlated with the electrophysiological study findings. RESULTS: The corrected sinus node recovery time and sinoatrial conduction time were abnormal in 6.9% and 26.1% of patients, respectively. Thirty-seven (32.2%) had abnormal atrioventricular conduction. Intraventricular conduction was abnormal in 39 (33.9%). Approximately 48% had induced sustained ventricular arrhythmias, most of which were monomorphic (83.6%). Right bundle branch block was the most common morphology (52.7%). Fifty-one percent were associated with symptoms/hemodynamic instability, 60% required electrical cardioversion, and 27.3% needed overdrive suppression. The most common site of origin was the left ventricular inferoseptal wall (18.2%), followed by the left ventricular posterobasal wall (11%). Patients with an ejection fraction<40% had a 1.94-fold increased risk of ventricular arrhythmias compared to those with an ejection fraction>60% (OR: 1.94; 95%CI: 1.12-3.38; p=0.01). The presence of complex ventricular arrhythmias on Holter did not predict inducible ventricular arrhythmias. CONCLUSIONS: Chagas patients with a low ejection fraction have an increased risk of inducible ventricular arrhythmias. Sinus node dysfunction, and atrioventricular node and His-Purkinje conduction abnormalities occur in about one-third of patients. Complex ventricular arrhythmias on Holter were not associated with an increased risk of inducible ventricular arrhythmias.

OBJECTIVES: N-3 polyunsaturated fatty acids have been proposed as a novel treatment for preventing postoperative atrial fibrillation due to their potential anti-inflammatory and anti-arrhythmic effects. However, randomized studies have yielded conflicting results. The objective of this study is to review randomized trials of N-3 polyunsaturated fatty acid use for postoperative atrial fibrillation. METHODS: Using the CENTRAL, PUBMED, EMBASE, and LILACS databases, a literature search was conducted to identify all of the studies in human subjects that reported the effects of N-3 polyunsaturated fatty acids on the prevention of postoperative atrial fibrillation in cardiac surgery patients. The final search was performed on January 30, 2011. There was no language restriction, and the search strategy only involved terms for N-3 polyunsaturated fatty acids (or fish oil), atrial fibrillation, and cardiac surgery. To be included, the studies had to be randomized (open or blinded), and the enrolled patients had to be >18 years of age. RESULTS: Four randomized studies (three double-blind, one open-label) that enrolled 538 patients were identified. The patients were predominantly male, the mean age was 62.3 years, and most of the patients exhibited a normal left atrial size and ejection fraction. N-3 polyunsaturated fatty acid use was not associated with a reduction in postoperative atrial fibrillation. Similar results were observed when the open-label study was excluded. CONCLUSIONS: There is insufficient evidence to suggest that treatment with N-3 polyunsaturated fatty acids reduces postoperative atrial fibrillation. Therefore, their routine use in patients undergoing cardiac surgery is not recommended.

Um homem de 56 anos veio à Clínica de Marcapasso para verificação de rotina de seu marcapasso. Ele havia apresentado um episódio de síncope na semana anterior. O paciente tinha um diagnostico prévio de cardiomiopatia hipertrófica (CMH) não-obstrutiva crônica. Devido a um episódio prévio de síncope e bloqueio infrahisiano 2:1 documentado, um marcapasso permanente de dupla câmara havia sido implantado alguns anos antes. O dispositivo foi verificado, mostrando vários episódios de altas freqüências ventriculares. Uma análise cuidadosa dos eletrogramas intracardíacos armazenados no dispositivo mostrou taquicardia ventricular (TV) com condução ventrículo-atrial 2:1. A seguinte exposição discute o diagnóstico alternativo e o manejo clínico em um diagnóstico não-usual de TV na presença de cardiomiopatia hipertrófica não-obstrutiva.

A 56-year-old man came to the Pacemaker Clinic for his regular pacemaker control. He had experienced a syncopal episode in the previous week. He had a previous diagnosis of non-obstructive hypertrophic cardiomyopathy. Due to a previous syncope and documented 2:1 infrahisian block, a dual-chamber permanent pacemaker had been implanted a few years before. The device was interrogated, showing several ventricular high rate episodes. A careful analysis of the stored intracardiac electrograms showed ventricular tachycardia (VT) with 2:1 ventriculoatrial conduction. The following presentation discusses the alternative diagnosis and clinical management in an unusual diagnosis of VT in the presence of non-obstructive hypertrophic cardiomyopathy.

Un varón de 56 anos vino a la Clínica de Marcapaso para verificación rutinaria de su marcapaso. Él había presentado un episodio de síncopa la semana anterior. El paciente tenía un diagnostico previo de cardiomiopatía hipertrófica (CMH) no obstructiva crónica. Un marcapaso permanente de doble cámara había sido implantado algunos años antes, en virtud de un episodio previo de síncopa y bloqueo infrahisiano documentado 2:1. Se verificó el dispositivo, que presentó varios episodios de altas frecuencias ventriculares. Un análisis cuidadoso de los electrogramas intracardiacos almacenados en el dispositivo reveló taquicardia ventricular (TV) con conducción ventrículo-atrial 2:1. La presente exposición discute el diagnóstico alternativo y el manejo clínico en un diagnóstico no usual de TV en la presencia de cardiomiopatía hipertrófica no obstructiva.

Chronic ventricular lead dislodgement is an infrequent complication of pacemaker implantation. Occasionally, the dislodged lead may sense and capture a chamber in which the lead was not originally positioned. Intracardiac real time electrograms and channel markers are useful tools for the diagnosis of pacemaker malfunction. We present the case of a patient with a ventricular lead dislodgement into the atrium. The ventricular lead was able to sense and capture the atrium. Initial diagnosis was performed based on the deductive analysis of intracardiac real time electrograms and channel markers and confirmed by chest X-ray.

El desplazamiento crónico del catéter ventricular es una complicación infrecuente del implante de marcapasos. Es infrecuente que un catéter desplazado sense y capture en una cámara donde no fue implantado originalmente. Se presenta el caso de un paciente con marcapasos doble cámara en el que el catéter ventricular se desplazó hacia la aurícula derecha. El catéter desplazado permite sensar y capturar la aurícula. El diagnóstico inicial se realizó mediante el análisis deductivo conjunto de los electrogramas en tiempo real y los eventos en los canales de registro ("marker channel"). La radiografía de tórax confirmó el diagnóstico presuntivo.

The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2) and TLR4 gene polymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln) polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6% and 1.8% respectively). The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.

Antecedentes: el déficit de estrógenos propio de la etapa postmenopáusica, puede contribuir al desarrollo de un disbalance autonómico con la reducción del reflejo cardiovagal, lo que a su vez puede incrementar el riesgo cardiovascular. Aún no se han aclarado en su totalidad los mecanismos fisiopatológicos subyacentes de esta alteración. En este artículo se discute el efecto de la terapia hormonal de reemplazo sobre la función autonómica en mujeres sometidas a histerectomía. Métodos: en este ensayo clínico cruzado, placebo-controlado, doble ciego, se incluyeron mujeres con histerectomía y amenorrea al menos un año antes de la cirugía. De forma aleatoria, recibieron estrógenos conjugados 0,625 mg/dL o placebo durante doce semanas, con un período intermedio sin medicación de dos semanas. Se evaluó la función autonómica cardiovagal y vascular mediante técnicas convencionales y a tráves de pletismografía por oclusión venosa para calcular el flujo sanguíneo en el antebrazo y la resistencia vascular periférica en condiciones basales, durante la prueba de mesa basculante y en la prueba de presión negativa en miembros inferiores. Resultados: no se encontraron diferencias en la función autonómica cardiovagal entre los grupos de tratamiento en condiciones de reposo ni durante la prueba de mesa basculante y presión negativa en miembros inferiores. Se documentaron diferencias significativas tanto en el flujo sanguíneo en el antebrazo [1,9(0,5) vs. 1,5(0,5), p=0,02]así como en la resistencia vascular periférica [53,5(18,2) vs. 68,6(34), p=0,02], al comparar terapia de reemplazo hormonal con placebo. Conclusiones: la terapia de reemplazo hormonal a corto plazo, no mejoró las respuestas reflejas autonómicas cardiovasculares en mujeres postmenopáusicas, pero sí incrementó la relajación vascular por reducción de la resistencia vascular periférica. La terapia de reemplazo hormonal puede utilizarse bajo supervisión adecuada para mejorar los síntomas de la menopausia durante un tiempo corto, principalmente en mujeres postmenopáusicas jóvenes no hipertensas.

Background: estrogen deficit during menopause may be related to cardiac autonomic function imbalance, reducing the cardiovagal reflex response that could potentially increase cardiovascular risk. The physiological mechanisms that lead to this alteration in postmenopausal women remain unclear. In this article, the effect of hormonal replacement therapy on autonomic function in women submitted to hysterectomy is discussed. Methods: Fifty women with a previous hysterectomy and amenorrhea for 1 year prior to surgery were enrolled in a prospective randomized crossover double-blind placebo controlled trial. Either oral estrogen replacement therapy (ERT) conjugated estrogens 0.625 mg once a day or placebo, were randomly administered in a crossover design during 12 weeks with a 2 week washout period. Cardiovagal autonomic function was assessed by conventional techniques and through venous occlusion plethysmography in order to evaluate vascular autonomic function calculating forearm blood flow (FBF) and peripheral vascular resistance (PVR) at baseline, and during head-up tilt (HUT) and a non-hypotensive stimuli (-10mmHg) lower-body negative pressure (LBNP). Results: No differences were found in cardiovagal autonomic function comparing ERT vs. placebo at baseline resting conditions, nor during HUT and LBNP. A significant difference was identified in supine FBF [1.9(0.5) vs. 1.5(0.5), p=0.02] as well as in PVR [53.5(18.2) vs. 68.6(34), p=0.02] comparing ERT vs. placebo interventions. Conclusions: Short term ERT did not improve cardiovascular autonomic reflex responses in postmenopausal women, but increased vascular relaxation primarily by reducing peripheral vascular resistance. Hormone replacement therapy can be used under adequate supervision in order to improve menopausal symptoms during a short period of time, mainly in young non-hypertensive post-menopausal women.

Introducción: la enfermedad de Chagas es una infección parasitaria ocasionada por el Trypanosoma cruzi. En Latinoamérica esta enfermedad es endémica, y la cardiomiopatía chagásica es su manifestación más frecuente en Colombia. Este artículo describe las principales características clínicas, electrocardiográficas y ecocardiográficas de la cardiomiopatía chagásica en el Departamento de Santander, Colombia. Materiales y métodos: se realizó un estudio descriptivo, transversal, de sujetos provenientes de Santander, entre los 18 y 80 años, seropositivos para T. cruzi, con síntomas de falla cardiaca no terminal. A estos pacientes se les realizó examen físico, electrocardiograma y ecocardiograma bidimensional. Resultados: se evaluaron 119 pacientes, 62 mujeres y 57 hombres, con edad promedio de 58,5 ± 10,7 años. Los antecedentes más frecuentes fueron: hipertensión arterial (49,6%), implantación de marcapaso (8,4%) y dislipidemia (7,6%). En 34,3% de los sujetos se encontró hipertrofia ventricular izquierda en asociación con trastornos de repolarización. De las anormalidades de conducción, el bloqueo de rama derecha fue el más frecuente (11,8%). La valvulopatía más común fue la insuficiencia mitral (61,5%). Ninguna de estas variables se asoció con un peor estado de clase funcional. Discusión: las características electrocardiográficas de la cardiomiopatía chagásica en Colombia, parecen tener un comportamiento diferencial por regiones, y para la zona del Departamento de Santander lo más usual es el hallazgo de hipertrofia ventricular izquierda, trastornos de repolarización y bloqueo de rama derecha. Las intervenciones tempranas en este grupo de pacientes son necesarias dado el alto costo social y económico que conlleva la cardiomiopatía chagásica.

Background: Chagas’ disease (CD) is a parasitic infection caused by the Trypanosoma cruzi. In Latin America the disease is endemic and Chagas’ cardiomyopathy(CCM) is the main clinical presentation of CD in Colombia. This article describes the main clinical, electrocardiographic and echocardiographic characteristics of the CCM in Santander, Colombia. Materials and methods: A cross-sectional study of patients of ages between 18 and 80 years, from the Department of Santander, Colombia, with positive serology for T. cruzi, and symptoms of non-terminal heart failure was performed. Physical examination, 12-lead electrocardiogram and 2D echocardiogram were carried out. Results: The study included 62 women and 57 men, mean age 58.5±10.7 years. Hypertension (49.6%), pacemaker implantation (8.4%) and dyslipidemia (7.6%) were the most frequent antecedents. Left ventricular hypertrophy was seen in 34.3% of the subjects and it was associated to abnormalities in re-polarization. Right bundle branch block was determined in 11.8% of the subjects. Mitral insufficiency was identified by echocardiogram in 61.5% of the participants. None of these variables were associated with a worse functional class state. Discussion: The electrocardiographic characteristics in patients with CCM in Colombia seem to have a different behaviour according to the regions, and for Santander the most frequent findings were left ventricular hypertrophy, abnormalities in repolarization and right bundle branch block. Early interventions on this group of patients are necessary in order to reduce the social and economic impact associated to the CCM.