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Abstract Background Anemia represents a commonly reported comorbidity in patients diagnosed with heart failure (HF), related with a higher risk of unfavorable outcomes such as recurrent hospitalizations and mortality. There is a lack of evidence in Latin America regarding this topic. Our aim was to evaluate the prognostic value of the diagnosis of anemia in patients from the Colombian Heart Failure Registry (RECOLFACA). Methods RECOLFACA registry included adult ambulatory patients with HF in 60 medical centers in Colombia during 2017–2019. Baseline characteristics of patients diagnosed with anemia and those without anemia were compared. The main outcome was all-cause mortality. A Cox proportional hazards regression model was used to evaluate the factors linked to the main outcome in patients with anemia. A statistically significant p-value was

Introduction. Heart failure and type 2 diabetes mellitus are critical public health issues. Objective. To characterize the risk factors for mortality in patients with heart failure and type 2 diabetes mellitus from a large registry in Colombia and to evaluate the potential effect modifications by type 2 diabetes mellitus over other risk factors. Materials and methods. Heart failure patients with and without type 2 diabetes mellitus enrolled in the Registro Colombiano de Falla Cardíaca (RECOLFACA) were included. RECOLFACA enrolled adult patients with heart failure diagnosis from 60 medical centers in Colombia during 2017-2019. The primary outcome was all-cause mortality. Survival analysis was performed using adjusted Cox proportional hazard models. Results. A total of 2514 patients were included, and the prevalence of type 2 diabetes mellitus was 24.7% (n = 620). We found seven independent predictors of short-term mortality for the general cohort, chronic obstructive pulmonary disease, sinus rhythm, triple therapy, nitrates use, statins use, anemia, and hyperkalemia. In the type 2 diabetes mellitus group, only the left ventricle diastolic diameter was an independent mortality predictor (HR = 0.96; 95% CI: 0.93-0.98). There was no evidence of effect modification by type 2 diabetes mellitus on the relationship between any independent predictors and all-cause mortality. However, a significant effect modification by type 2 diabetes mellitus between smoking and mortality was observed. Conclusions. Patients with type 2 diabetes mellitus had higher mortality risk. Our results also suggest that type 2 diabetes mellitus diagnosis does not modify the effect of the independent risk factors for mortality in heart failure evaluated. However, type 2 diabetes mellitus significantly modify the risk relation between mortality and smoking in patients with heart failure.

Background: The value of Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitor) therapy in individuals with heart failure with preserved EF (HFpEF) was unknown until the EMPEROR-Preserved trial. We aimed to assess the proportion of patients with HFpEF that are eligible for empagliflozin therapy within the Colombian Heart Failure Registry (RECOLFACA). Methods: RECOLFACA enrolled adult patients with a HF diagnosis during 2017–2019 from 60 medical centers in Colombia. Criteria of the EMPEROR-Preserved Trial were used to recruit participants. The main outcome was individual eligibility with N-terminal pro-B-type natriuretic peptide (NT-proBNP) criteria, while the secondary outcome was eligibility without NT-proBNP data. Results: RECOLFACA had 799 patients with HFpEF (mean age70.7 ± 13.5; 50.7 % males). According to the major selection criteria of the EMPEROR Preserved Trial, 73.7 % patients would be eligible for empagliflozin therapy initiation when considering the NT-proBNP threshold. The NT-proBNP threshold represented the main determinant of ineligibility in patients with this biomarker measure (13.6 %; n = 16). In patients without NT-proBNP data, the main reasons for exclusion were the diagnosis of symptomatic hypotension or a systolic blood pressure below 100 mmHg (7.5 %), having an eGFR

Introduction: Arterial hypertension represents one of the main comorbidities observed in patients with heart failure (HF) and one of the main risk factors for its development. Despite this, studies assessing this hypertensive etiology are scarce in Latin America. Our objective was to analyze the prevalence of HF of hypertensive etiology and evaluate its prognosis in patients enrolled in the Colombian Heart Failure Registry (RECOLFACA by its Spanish acronym). Methods: RECOLFACA recruited adult patients diagnosed with HF in 60 centers in Colombia between 2017 and 2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess factors associated with primary outcomes in patients with hypertensive HF. A p value

The impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) has yet to be well assessed in the Latin American population. This study aimed to analyze the impact of COPD on HF patients from the Colombian Heart Failure Registry (RECOLFACA). The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of COPD on mortality. From the total of 2528 patients in the registry, 2514 patients had information regarding COPD diagnosis. COPD diagnosis was associated with a worse functional class and higher use of diuretics than non-COPD patients (p < 0.001). Patients with this comorbidity had a significantly better ejection fraction (median ejection fraction 35% vs. 32% in non-COPD patients; p = 0.004), with a higher occurrence of HF with preserved ejection fraction (HFpEF) in the COPD group (p = 0.000). Finally, patients with COPD had a significantly higher risk of mortality in the multivariate regression model (HR 1.47; 95% CI 1.02, 2.11). COPD is a prevalent comorbidity among patients with HF in Colombia, showing a different clinical profile and a worse functional class than patients without this condition. Patients with COPD and HFpEF have a high mortality risk according to our results.

El trasplante de órganos es una alternativa terapéutica cada vez más frecuente en nuestro medio y con ello las complicaciones y efectos de las medicaciones inmunosupresoras que afectan el sistema nervioso central (SNC). El síndrome de encefalopatía posterior reversible (SEPR) es un trastorno caracterizado por manifestaciones neurológicas potencialmente reversibles, asociadas a cambios en las neuroimágenes, en estrecha asociación con factores precipitantes, dentro de los cuales, se destacan el uso de medicamentos inmunosupresores, quimioterapéuticos y algunas condiciones médicas como hipertensión arterial y enfermedades renales. Las características clinico-radiológicas de este trastorno usualmente revierten con la suspensión de los factores precipitantes; sin embargo el diagnóstico tardío puede llevar a un desenlace fatal. Se presenta un caso de SEPR en una paciente joven a quien se le realizó trasplante cardiaco de urgencia. Durante su manejo post-operatorio recibió tacrolimus como parte del tratamiento del paciente trasplantado. En la cuarta semana de post-operatorio y quinto día de tratamiento con tacrolimus desarrolló cefalea asociada a cifras tensionales elevadas, deterioro de la conciencia y episodios convulsivos tónico-clónicos generalizados; las manifestaciones neurológicas revirtieron en las 48 horas siguientes al retiro del tacrolimus, al igual que los cambios en las neuroimagenes que resolvieron un mes después de las manifestaciones iniciales.

Background: There is a lack of epidemiological data around heart failure (HF) in Latin America; the potential impact description of this disease in middle-income countries is relevant. Objective: This study aimed to describe the characteristics and healthcare resource utilization patterns of HF patients at baseline and six-month follow-up. Methods: This retrospective observational study used data from the RECOLFACA ('Registro Colombiano de Falla Cardíaca') registry, which includes data obtained from the examination of clinical records from 2,528 patients in 60 Colombian healthcare institutions. Baseline and six-month follow-up data were evaluated from patients with previous hospital admissions due to HF during the 12 months prior to enrollment. Results: This study analyzed 2,045 patients (42.8% female) with a mean age of 67.71 ± 13.64 years. The most common etiologies were ischemic (44.4%) and hypertensive heart disease (38.5%). At baseline, 53.4% of patients were classified with NYHA class II, and 73.6% had a reduced left ventricle ejection fraction (LVEF). A year prior to entering the registry, patients were hospitalized an average of 1.4 ± 1.1 times due to HF. Prescription of evidence-based treatment at baseline included sacubitril/valsartan (10%), ACEI (33%), ARB (41%), beta-blocker (79%), diuretics (68%), and MRA (56%). The average quality of life score measured using the EQ-5D-3L questionnaire was 78.7 ± 20.8 at baseline and 82.3 ± 20.1 at the six-month follow-up. The mortality rate was 6.7%. Conclusions: The use of information from the RECOLFACA registry allowed characterization as well as analyses of healthcare resource utilization of patients with heart failure in Colombia. The results of this study show that multiple evidence-based treatments for HF are being widely used in Colombia, but there seems to be room for improvement regarding some interventions for the treatment of patients with HF.

Resumen: Las recomendaciones de las guías internacionales para el tratamiento de la insuficiencia cardiaca son similares para la población de pacientes con y sin diabetes. Sin embargo, existen análisis del subgrupo de diabéticos de muchas de las terapias actuales, que sugieren que esta población podría tener un comportamiento diferente, pues tiene mayor riesgo de eventos y puede presentar, a la vez, mayor número de complicaciones.En este artículo se resume el estado del arte actual de los tratamientos farmacológicos y de los dispositivos utilizados para los pacientes con insuficiencia cardiaca y se ilustran las diferencias que existen en la respuesta de los pacientes diabéticos. Abstract: The recommendations in the international guidelines for the treatment of heart failure are similar for the population with or without diabetes. However, an analysis of many of the current therapies has been performed on a sub-group of diabetics has suggested that this population could behave differently, as it has an increased risk of events and may also present with a greater number of complications.In this article, a summary is presented on the current state of the art of the pharmacological treatments and the devices used for patients with heart failure, as well as illustrating the differences in the response of diabetic patients. Palabras clave: Insuficiencia cardiaca, Diabetes, Tratamiento, Keywords: Heart failure, Diabetes, Treatment

BackgroundChagas disease (CD) is endemic in Latin America; however, its spread to nontropical areas has raised global interest in this condition. Barriers in access to early diagnosis and treatment of both acute and chronic infection and their complications have led to an increasing disease burden outside of Latin America. Our goal was to identify those barriers and to perform an additional analysis of them based on the Inter American Society of Cardiology (SIAC) and the World Heart Federation (WHF) Chagas Roadmap, at a country level in Argentina, Colombia, Spain, and the United States, which serve as representatives of endemic and nonendemic countries.Methodology and principal findingsThis is a nonsystematic review of articles published in indexed journals from 1955 to 2021 and of gray literature (local health organizations guidelines, local policies, blogs, and media). We classified barriers to access care as (i) existing difficulties limiting healthcare access; (ii) lack of awareness about CD and its complications; (iii) poor transmission control (vectorial and nonvectorial); (iv) scarce availability of antitrypanosomal drugs; and (v) cultural beliefs and stigma. Region-specific barriers may limit the implementation of roadmaps and require the application of tailored strategies to improve access to appropriate care.ConclusionsMultiple barriers negatively impact the prognosis of CD. Identification of these roadblocks both nationally and globally is important to guide development of appropriate policies and public health programs to reduce the global burden of this disease.

Resumen: La definición más actualizada de falla cardiaca avanzada incluye síntomas refractarios al tratamiento convencional, independiente de la fracción de eyección del ventrículo izquierdo, acompañados de elevación de péptidos natriuréticos. En esta nueva definición se destacan condiciones específicas como son la necesidad usual de diurético intravenoso, hospitalizaciones o consultas frecuentes por falla cardíaca, medicación inotrópica intermitente y arritmias malignas recurrentes.Esta condición está presente en aproximadamente 4 a 6% de los pacientes con falla cardiaca y se asocia a más síntomas, más comorbilidades y mayor mortalidad (hasta 75% a un año). En este punto, las terapias convencionales han fallado o son refractarias y se requiere la toma de decisiones para instaurar tratamientos más avanzados (p. ej.: inotrópicos, asistencia ventricular, trasplante cardiaco, cuidado paliativo, entre otras).El tratamiento representa un reto para los sistemas de salud de Colombia por la necesidad de optimizar y racionalizar el uso de estos recursos; por esto se debe considerar que estos pacientes, en algún momento de su evolución, que sean remitidos para valoración en las Clínicas de Falla Cardíaca ya que estos servicios cuentan con personal altamente calificado y una estructura administrativa, logística y tecnológica que garantizan el acceso a un tratamiento integral y multidisciplinario con estándares de calidad internacionales que es lo que finalmente se requiere en estas condiciones.En el “Consenso colombiano de falla cardiaca avanzada” se presentan diferentes opciones de tratamiento a considerar y un modelo de atención integral que inicia desde el momento del diagnóstico hasta etapas refractarias y avanzadas. Abstract: The most up-to-date definition of advanced heart failure includes symptoms refractory to conventional treatment (regardless of the left ventricular ejection fraction), accompanied by an elevation in natriuretic peptides. Specific conditions are highlighted in this new definition, such as the usual need of an intravenous diuretic, hospital admissions, or frequent consultations due to heart failure, intermittent inotropic medication, and recurrent malignant arrhythmias.This condition is present in approximately 4 to 6% of patients with heart failure and is associated with more symptoms, more comorbidities, and higher mortality (up to 75% at one year). On this point, the conventional treatments have failed, or are refractory, and decisions need to be taken to introduce more advanced treatments (for example: inotropic, ventricular assistance, palliative care, among others).The treatment represents a challenge for the Health Systems of Colombia due to the need to optimise and rationalise the use of these resources. For this reason, it must be considered that these patients, at any time during its course, may be sent for assessment in Heart Failure Clinics, as these services have highly qualified staff and an administrative, logistics, and technological structure that ensures access to an integral and multidisciplinary treatment with standards of international quality, which is what is finally required in these conditions.Different treatment options to consider are presented in the “Colombian consensus on advanced heart failure”, as well as an integral care model that begins from the time of the diagnosis until the refractory and advanced stages. Palabras clave: Avanzada, Tratamiento, Clínicas, Inotrópicos, Trasplante, Paliativo, Enfermería, Key words: Advanced, Treatments, Clinics, Inotropes, Transplant, Palliative, Nursing

Aim: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). Methods: A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry. Results: Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group. Conclusions: CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.

As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. 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.

Background: Chagas Disease is a neglected tropical disease caused by the protozoan 'Trypanosoma cruzi', with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality asso­ciated with the disease, the social and economic burdens on individuals and society are substantial. Often called the ‘silent killer’, Chagas disease is characterized by a long, asymptomatic phase in affected individuals. Approximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure. Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American Society of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care profession­als working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation. Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of ‘roadblocks’ in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy. Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on avail­able research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.

Tyrosine kinase 2 (TYK2) is a member of the Janus kinases family implicated in the signal transduction of type I interferons and several interleukins. It has been described that genetic mutations within TYK2 lead to multiple deleterious effects in the immune response. In this work, we have analyzed three functional independent variants from the frequency spectrum on the TYK2 gene (common and low-frequency variants) suggested to reduce the function of the gene in mediating cytokine signaling and the susceptibility to infections by Trypanosoma cruzi and/or the development of Chagas cardiomyopathy in the Colombian population. A total of 1,323 individuals from a Colombian endemic region for Chagas disease were enrolled in the study. They were classified as seronegative (n = 445), seropositive asymptomatic (n = 336), and chronic Chagas Cardiomyopathy subjects (n = 542). DNA samples were genotyped using TaqMan probes. Our results showed no statistically significant differences between the allelic frequencies of the three analyzed variants when seropositive and seronegative individuals were compared, therefore these variants were not associated with susceptibility to Chagas disease. Moreover, when Chagas cardiomyopathy patients were compared to asymptomatic patients, no significant associations were found. Previous reports highlighted the association of this gene in immune-related disorders under an autoimmunity context, but not predisposing patients to infectious diseases, which is consistent with our findings. Therefore, according to our results, TYK2 gene variants do not seem to play an important role in Chagas disease susceptibility and/or chronic Chagas cardiomyopathy.

Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

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.

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.