Impact of an online course on enhancing the diagnosis of Chagas disease in Latin America.

Objective: Chagas disease poses a public health problem in Latin America, and the electrocardiogram is a crucial tool in the diagnosis and monitoring of this pathology. In this context, the aim of this study was to quantify the change in the ability to detect electrocardiographic patterns among healthcare professionals after completing a virtual course. Materials and Methods: An asynchronous virtual course with seven pre-recorded classes was conducted. Participants answered the same questionnaire at the beginning and end of the training. Based on these responses, pre and post-test results for each participant were compared. Results: The study included 1656 participants from 21 countries; 87.9% were physicians, 5.2% nurses, 4.1% technicians, and 2.8% medical students. Initially, 3.1% answered at least 50% of the pre-test questions correctly, a proportion that increased to 50.4% after the course (p=0.001). Regardless of their baseline characteristics, 82.1% of course attendees improved their answers after completing the course. Conclusions: The implementation of an asynchronous online course on electrocardiography in Chagas disease enhanced the skills of both medical and non-medical personnel to recognize this condition.

A systematic review and meta-analysis of mortality in chronic Chagas cardiomyopathy versus other cardiomyopathies: higher risk or fiction?

INTRODUCTION AND OBJECTIVES: Although multiple studies suggest that chronic Chagas cardiomyopathy (CCC) has higher mortality than other cardiomyopathies, the absence of meta-analyses supporting this perspective limits the possibility of generating robust conclusions. The aim of this study was to systematically evaluate the current evidence on mortality risk in CCC compared with that of other cardiomyopathies. METHODS: PubMed/Medline and EMBASE were searched for studies comparing mortality risk between patients with CCC and those with other cardiomyopathies, including in the latter nonischemic cardiomyopathy (NICM), ischemic cardiomyopathy, and non-Chagas cardiomyopathy (nonCC). A random-effects meta-analysis was performed to combine the effects of the evaluated studies. RESULTS: A total of 37 studies evaluating 17 949 patients were included. Patients with CCC had a significantly higher mortality risk compared with patients with NICM (HR, 2.04; 95%CI, 1.60-2.60; I2, 47%; 8 studies) and non-CC (HR, 2.26; 95%CI, 1.65-3.10; I2, 71%; 11 studies), while no significant association was observed compared with patients with ischemic cardiomyopathy (HR, 1.72; 95%CI, 0.80-3.66; I2, 69%; 4 studies) in the adjusted-measures meta-analysis. CONCLUSIONS: Patients with CCC have an almost 2-fold increased mortality risk compared with individuals with heart failure secondary to other etiologies. This finding highlights the need for effective public policies and targeted research initiatives to optimally address the challenges of CCC.

Characteristics and Outcomes of Atrial Fibrillation in Chronic Heart Failure Patients: A Comprehensive Analysis of the Colombian Heart Failure Registry.

Background: Heart failure (HF) and atrial fibrillation (AF) represent conditions that commonly coexist. The impact of AF in HF has yet to be well studied in Latin America. This study aimed to characterize the sociodemographic and clinical features, along with patients' outcomes with AF and HF from the Colombian Heart Failure Registry (RECOLFACA). Methods: Patients with ambulatory HF and AF were included in RECOLFACA, mainly with persistent or permanent AF. A 6-month follow-up was performed. Primary outcome was all-cause mortality. To assess the impact of AF on mortality, we used a logistic regression model. A P value of < 0.05 was considered significant. All statistical tests were two-tailed. Results: Of 2,528 patients with HF in the registry, 2,514 records included information regarding AF diagnosis. Five hundred sixty (22.3%) were in AF (mean age 73 ± 11, 56% men), while 1,954 had no AF (mean age 66 ± 14 years, 58% men). Patients with AF were significantly older and had a different profile of comorbidities and implanted devices compared to non-AF patients. Moreover, AF diagnosis was associated with lower quality of life score (EuroQol-5D), mainly in mobility, personal care, and daily activity. AF was prevalent in patients with preserved ejection fraction (EF), while no significant differences in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were observed. Although higher mortality was observed in the AF group compared to individuals without AF (8.9% vs. 6.1%, respectively; P = 0.016), this association lost statistical significance after adjusting by age in a multivariate regression model (odds ratio (OR): 1.35; 95% confidence interval (CI): 0.95 - 1.92). Conclusions: AF is more prevalent in HF patients with higher EF, lower quality of life and different clinical profiles. Similar HF severity and non-independent association with mortality were observed in our cohort. These results emphasize the need for an improved understanding of the AF and HF coexistence phenomenon.

Clinical Characteristics and Outcomes of Patients with Heart Failure of Hypertensive Etiology: Analysis of Colombian Heart Failure Registry (RECOLFACA).

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 <0.05 was considered significant. All statistical tests were two-tailed. RESULTS: Out of the total number of patients evaluated in RECOLFACA (n = 2,514), 804 had a diagnosis of HF with hypertensive etiology (31.9%). These patients were less frequently males and had a significantly older age and lower prevalence of comorbidities than those with HF of other etiologies. Additionally, patients with hypertensive HF had a higher prevalence of HF with preserved ejection fraction (HFpEF) (34.1% vs. 28.3%; p = 0.004). Finally, type 2 diabetes mellitus, chronic obstructive pulmonary disease diagnosis, and NYHA class IV were classified as independent mortality risk factors. CONCLUSIONS: Hypertensive HF represents about one-third of the total number of patients with HF in RECOLFACA. Compared with HF of other etiologies, it presents a differential clinical profile - older age and a higher prevalence of HFpEF. RECOLFACA has become a useful tool to characterize patients with HF in Colombia, with which it has been possible to carry out a more specific search and reach the diagnosis of this pathology in our population, and it has served as an example to stimulate registries of patients with HF in other countries in the region.

Adherence to treatment guidelines in Ambulatory Heart Failure Patients with Reduced Ejection Fraction in a Latin-American Country: Observational Study of the Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) or angiotensin receptor - neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA), and sodium-glucose cocotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aims to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA). METHODS: Patients with HFrEF enrolled in RECOLFACA during 2017-2019 were included. Heart Failure (HF) medications prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists. RESULTS: Out of 2528 patients in the registry, 1384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists. CONCLUSION: Prescription rates and target dose achievement is sub-optimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.

The Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared With Outpatients With HFrEF: An Analysis of GALACTIC-HF.

BACKGROUND: In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events, or cardiovascular death in patients with HF and reduced ejection fraction. The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting, that is, whether participants were enrolled as outpatients or inpatients. METHODS AND RESULTS: Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department visit). The primary outcome was a composite of worsening HF event (HF hospitalization or an urgent emergency department or clinic visit) or cardiovascular death. Of the 8232 patients analyzed, 2084 (25%) were hospitalized at randomization. Hospitalized patients had higher N-terminal prohormone of B-type natriuretic peptide concentrations, lower systolic blood pressure, reported more symptoms, and were less frequently treated with a renin-angiotensin system blocker or a beta-blocker than outpatients. The rate (per 100 person-years) of the primary outcome was higher in hospitalized patients (placebo group = 38.3/100 person-years) than in outpatients (23.1/100 person-years); adjusted hazard ratio 1.21 (95% confidence interval 1.12-1.31). The effect of omecamtiv mecarbil versus placebo on the primary outcome was similar in hospitalized patients (hazard ratio 0.89, 95% confidence interval 0.78-1.01) and outpatients (hazard ratio 0.94, 95% confidence interval 0.86-1.02) (interaction P = .51). CONCLUSIONS: Hospitalized patients with HF with reduced ejection fraction had a higher rate of the primary outcome than outpatients. Omecamtiv mecarbil decreased the risk of the primary outcome both when initiated in hospitalized patients and in outpatients.

Chronic hyperkalemia, diagnosis and management. Colombian consensus.

OBJECTIVE: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. METHOD: This consensus was made by nephrologists and cardiologists following the GRADE methodology. RESULTS: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. CONCLUSIONS: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

OBJETIVO: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. MÉTODO: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. RESULTADOS: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. CONCLUSIONES: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Characterization of Patients With Heart Failure of Chagas Etiology in Colombia: An Analysis Based on the Colombian Registry of Heart Failure (RECOLFACA).

Chronic Chagas cardiomyopathy (CCM) represents a relevant origin of Heart Failure (HF) in countries where the disease is endemic. CCM exhibits distinct myocardial involvement and is associated with a poorer prognosis compared to different HF etiologies. The aim is to explain the features and prognosis of individuals with HF resultant to CCM registered in the Colombian Registry of Heart Failure (RECOLFACA). RECOLFACA registry enrolled 2528 adult patients with HF. A comparison was made between patients diagnosed with CCM and those diagnosed with other etiologies of HF. Eighty-eight patients (3.5%) present CCM diagnosis. The individuals diagnosed with both HF and CCM were notably younger in age, had less comorbidities, poorer functional class, and significantly inferior ejection fraction. Finally, the presence of CCM diagnosis was linked to a substantially elevated mortality risk throughout the follow-up period (HR 2.01; 95% CI, 1.01-4.00) according to a multivariate model adjusted. CCM represents an important etiology of HF in Colombia, drawing attention to a distinct clinical profile and a higher risk of mortality compared to other HF etiologies.

Prevalence, Clinical Characteristics, and Prognostic Impact of Kidney Disease on Heart Failure Patients: An Observational Study of the Colombian Heart Failure Registry.

INTRODUCTION: Chronic kidney disease (CKD) represents one of the most frequent comorbidities observed in heart failure (HF) patients and has been observed to increase this population's risk of adverse outcomes. Nevertheless, evidence analyzing kidney dysfunction in HF is scarce in Latin American populations. We aimed to analyze the prevalence of kidney dysfunction and assess its association with mortality in patients diagnosed with HF enrolled in the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of the different categories of eGFR in mortality risk. A p value of <0.05 was considered significant. All statistical tests were two-tailed. RESULTS: From the total 2,514 evaluated patients, 1,501 (59.7%) patients had moderate kidney dysfunction (eGFR <60 mL/min/1.73 m2), while 221 (8.8%) patients were classified as having a severe kidney dysfunction (eGFR <30 mL/min/1.73 m2). Patients with lower kidney function were most commonly males, had higher median age, and reported a higher prevalence of cardiovascular comorbidities. Moreover, different patterns of medications prescription were observed when comparing CKD versus non-CKD patients. Finally, eGFR <30 mL/min/1.73 m2 was significantly associated with a higher mortality risk compared to eGFR >90 mL/min/1.73 m2 status (HR: 1.87; 95% CI, 1.10-3.18), even after an extensive adjustment by relevant covariates. CONCLUSION: CKD represents a prevalent condition in the setting of HF. Patients with CKD and HF present with multiple sociodemographic, clinical, and laboratory differences compared with those only diagnosed with HF and present a significantly higher risk of mortality. A timely diagnosis and optimal treatment and follow-up of CKD in the setting of HF may improve the prognosis of these patients and prevent adverse outcomes.

Prevalence of Neutralizing Antibodies against Adeno-Associated Virus Serotypes 1, 2, and 9 in Non-Injected Latin American Patients with Heart Failure-ANVIAS Study.

Neutralizing antibody (NAb) activity against the viral capsid of adeno-associated viral (AAV) vectors decreases transduction efficiency, thus limiting transgene expression. Several reports have mentioned a variation in NAb prevalence according to age, AAV serotype, and, most importantly, geographic location. There are currently no reports specifically describing the anti-AAV NAb prevalence in Latin America. Here, we describe the prevalence of NAb against different serotypes of AAV vectors (AAV1, AAV2, and AAV9) in Colombian patients with heart failure (HF) (referred to as cases) and healthy individuals (referred to as controls). The levels of NAb were evaluated in serum samples of 60 subjects from each group using an in vitro inhibitory assay. The neutralizing titer was reported as the first dilution inhibiting ≥50% of the transgene signal, and the samples with neutralizing titers at ≥1:50 dilution were considered positive. The prevalence of NAb in the case and control groups were similar (AAV2: 43% and 45%, respectively; AAV1 33.3% in each group; AAV9: 20% and 23.2%, respectively). The presence of NAb for two or more of the serotypes analyzed was observed in 25% of the studied samples, with the largest amount in the positive samples for AAV1 (55-75%) and AAV9 (93%), suggesting serial exposures, cross-reactivity, or coinfection. Moreover, patients in the HF group exhibited more common combined seropositivity for NAb against AAV1 d AAV9 than those in the control group (91.6% vs. 35.7%, respectively; p = 0.003). Finally, exposure to toxins was significantly associated with the presence of NAb in all regression models. These results constitute the first report of the prevalence of NAb against AAV in Latin America, being the first step to implementing therapeutic strategies based on AAV vectors in this population in our region.

Comorbidity profile and outcomes in patients with chronic heart failure in a Latin American country: Insights from the Colombian heart failure registry (RECOLFACA).

BACKGROUND: Heart failure (HF) is usually accompanied by cardiovascular and non-cardiovascular comorbidities, which may significantly impact its prognosis. In this study we aimed to characterize the comorbidity profile and its impact in mortality in patients with HF diagnosis from the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess the impact of the comorbidities in mortality. A p-value of <0.05 was considered significant. RESULTS: From the total 2528 patients included in the registry, 2514 patients (58% males, mean age 68 years) had information regarding comorbidity diagnoses. 2321 patients (92.3%) reported at least one comorbidity. Arterial hypertension was the most frequent individual diagnosis (72%; n = 1811), followed by anemia (30.1%, n = 726). The most frequently observed coexisting comorbidities were coronary disease (CHD) with dyslipidemia, and chronic kidney disease (CKD) with type 2 Diabetes Mellitus (T2DM). Different patterns of comorbidity coexistence were observed when comparing HF patients by sex and left-ventricular ejection fraction (LVEF) classification. The only comorbidities that were significantly associated with mortality after multivariate adjustment were T2DM (HR 1.45. 95% CI 1.01-2.12), anemia (HR 1.48. 95% CI 1.02-2.16), and CHD (HR 1.59. 95% CI 1.09-2.33). CONCLUSION: Multiple comorbidities were frequently observed in the patients from the RECOLFACA. T2DM, anemia and CHD were significantly associated with a higher risk of mortality, highlighting the importance of promoting an optimal follow-up and control of these conditions.

Hiperkalemia crónica, diagnóstico y manejo. Consenso colombiano / Chronic hyperkalemia, diagnosis and management. Colombian consensus

Resumen Objetivo: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. Método: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. Resultados: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. Conclusiones: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Abstract Objective: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. Method: This consensus was made by nephrologists and cardiologists following the GRADE methodology. Results: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. Conclusions: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy.

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.

Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients. OBJECTIVES: This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. METHODS: Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death. RESULTS: A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (Pinteraction = 0.002) and total heart failure hospitalizations (Pinteraction < 0.001), with those most frail deriving greater benefit. CONCLUSIONS: Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Global, Regional, and National Trends of Chagas Disease from 1990 to 2019: Comprehensive Analysis of the Global Burden of Disease Study.

Background: Chagas disease (CD) is a neglected tropical disease, endemic in Latin America, but due to migration and environmental changes it has become a global public health issue. Objectives: To assess the global prevalence and disability-adjusted life years due to CD using findings from the Global Burden of Disease Study 2019. Methods: The Global Burden of Disease data was obtained from the Global Burden of Disease Collaborative Network; results were provided by the Institute for Health Metrics and Evaluation. The prevalence and disability-adjusted life-years (DALYs) were described at a global, regional, and national level, including data from 1990 to 2019. Results: Globally, CD prevalence decreased by 11.3% during the study period, from 7,292,889 cases estimated in 1990 to 6,469,283 in 2019. Moreover, the global DALY rate of CD decreased by 23.7% during the evaluated period, from 360,872 in 1990 to 275,377 in 2019. In addition, significant differences in the burden by sex, being men the most affected, age, with the elderly having the highest burden of the disease, and sociodemographic index (SDI), with countries with the lowest SDI values having the highest prevalence of the disease, were observed. Finally, the prevalence trends have followed different patterns according to the region, with a sustained decrease in Latin America, compared to an increasing trend in North America and Europe until 2010. Conclusion: The global burden of CD has changed in recent decades, with a sustained decline in the number of cases. Although the majority of cases remain concentrated in Latin America, the increase observed in countries in North America and Europe highlights the importance of screening at-risk populations and raising awareness of this neglected tropical disease.

Characteristics and Outcomes of Heart Failure Patients from a Middle-Income Country: The RECOLFACA Registry.

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.

Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy.

Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.