Health insurance and clinical outcomes in patients with chronic heart failure in Latin America: an observational study of the Colombian Heart Failure Registry (RECOLFACA).

The effect of the health insurance type on the prognosis of heart failure (HF) patients in Colombia and Latin America is poorly known. We aimed to analyze the characteristics of HF patients that participated in the Colombian Heart Failure Registry (RECOLFACA) as stated by their health insurance type and their relationship with the immediate prognosis of these patients. Patients with HF diagnosis were included in the RECOLFACA registry between 2017-2019. The registry was conducted in 60 centers in Colombia. All-cause mortality was the principal outcome. To evaluate the impact of health insurance on mortality, a Cox proportional hazards regression model was used. The Kaplan-Meier analysis was performed to compare survival probabilities according to insurance type. All statistical analyses were two-tailed and were considered significant with a p value < 0.05. Of the 2,528 participants enrolled in the registry, 99% held details about their health insurance. Of those, 897 patients (35.6%) were covered by public insurance. These patients were significantly younger, with a lower proportion of men, more frequently from rural origin, and lower prevalence of most comorbidities (omitting hypertension, chronic obstructive pulmonary disease (COPD), and Chagas disease) than those with private insurance. Furthermore, patients with public insurance had a worse functional class, as well as a poorer quality of life, and lower frequency of use of implantable devices, while exhibiting similar prescription rates of triple medical therapy for HF. Finally, no differences in short-term mortality were observed between the two groups (HR 1.09; 95% CI 0.79, 1.51). The type of health insurance represents a condition related with relevant differences in the profile of patients with HF in Colombia. Despite this, no significant differences were detected in the short-term prognosis of these patients based on the type of health insurance.

Advancing Cardiac Care: A Registry of Heart Transplantation in Latin America (1968-2022).

INTRODUCTION: Heart transplantation (HTx) has emerged as a pivotal intervention for end-stage heart failure, offering significant improvements in survival and quality of life. This manuscript elucidates the landscape of HTx across Latin America (LATAM) from its advent in 1968 through December 2022, shedding light on its evolution, current practices, and regional disparities. METHODS: We distributed a structured questionnaire to the national coordinators or representatives of the Interamerican Council of Heart Failure and Pulmonary Hypertension, collating responses from 20 LATAM nations. This approach facilitated a comprehensive aggregation of regional HTx data. RESULTS: A total of 12,374 HTx were performed in 166 centers across 16 LATAM countries, with Brazil, Argentina, and Colombia accounting for the majority of procedures. Pediatric transplants represented 9% of the total caseload, and combined organ transplants were reported in 62.5% of the participating countries, underscoring the complexity and breadth of transplant services in the region. CONCLUSION: Despite facing infrastructural and logistical challenges, LATAM has demonstrated a robust capacity to conduct high-complexity transplant procedures. The establishment of a structured, regional HTx registry is imperative to enhance data collection and analysis, which in turn can inform clinical decision-making and policy development, ultimately improving patient outcomes across the continent.

How can we optimize the diagnostic and therapeutic approach to pneumonia? Expert opinion-based recommendations.

Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations.

SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art.

Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group's mechanism of action.

Quality of Life is an Independent Predictor of Mortality in Patients with Heart Failure: A Prospective Cohort Study from the Colombian Heart Failure Registry (RECOLFACA).

AIM: Patients with Heart Failure (HF) commonly have poor quality of life (QoL), secondary to the persistence and severity of HF symptoms. We aimed to evaluate the prognostic value of QoL measures on all-cause mortality in patients with HF from the Colombian registry of heart failure (RECOLFACA). METHODS AND RESULTS: We analyzed data from patients registered in RECOLFACA during 2017-2019. QoL was measured using the EuroQol-5D questionnaire (EQ-5D). From the questionnaire, two independent predictors of mortality were obtained, the visual analogue scale (VAS) and the utility score (US). Primary outcome was all-cause mortality, and secondary variables evaluated were demographic factors, comorbidities, NYHA classification, medications used and laboratory test results. To analyze survival among patients, the Kaplan-Meier method and the hierarchical Cox proportional-hazards regression model were used. This study included 2514 patients from RECOLFACA. Most patients were male (57.6%), and mean age was 67.8 years. Mean value and standard deviation (SD) of the VAS score was 78.8 ± 20.1 points, while the mean and SD of the US score was 0.81 ± 0.20. As the Kaplan-Meier curve illustrated, patients in the lower quartiles of both VAS and US scores had a significantly higher probability of mortality (log-rank test: p<0.001 for both scores). CONCLUSION: QoL, as calculated by the EQ-5D questionnaire, served as an independent predictor of mortality in patients from RECOLFACA. Further studies may be needed to evaluate whether provision of optimizing therapies and follow-up care based on patients' perceived QoL reduces short- and long-term mortality rates in this population.

Impact of sex on clinical and laboratory parameters in patients with heart failure: insights from the Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. This study aimed to assess the impact of sex on sociodemographic, clinical, and laboratory parameters in patients with HF who were included in the Colombian Heart Failure Registry (RECOLFACA). METHODS: This was a cross-sectional analytical research. All 2528 patients included in RECOLFACA were analysed. The Mann-Whitney U test was used to compare median values as well as first and third quartiles (Q1-Q3). The age-related trend of NT-proBNP levels for both men and women groups was statistically evaluated. RESULTS: The study included 2528 patients with HF (1072 women and 1456 men). The echocardiographic evidence showed that men presented reduced left ventricular ejection fraction (LVEF) (79.63 vs. 69.75%, respectively; p < 0.001) more often than women, which had a significantly higher proportion of preserved LVEF (20.46 vs.11.24%, respectively; p < 0.001). Women displayed a higher value of systolic blood pressure (p < 0.001) and heart rate (p = 0.014) compared to men. Haemoglobin, creatinine, and sodium levels were significantly higher in men. Men had a considerably lower glomerular filtration rate value, with the median reaching a G3a value for chronic renal failure. According to age, the levels of NT-proBNP in each sex increased equivalently with age. CONCLUSION: Sex differences presented in this study are comparable to those discovered in other nations. However, certain variations show that these sex differences may differ by geographical area, which should encourage further investigations to describe them.

The Role and Implications of COVID-19 in Incident and Prevalent Heart Failure.

PURPOSE OF REVIEW: This review examines the pathophysiological interactions between COVID-19 and heart failure, highlighting the exacerbation of heart failure in COVID-19 patients. It focuses on the complex mechanisms driving worse outcomes in these patients. RECENT FINDINGS: Patients with pre-existing heart failure experience more severe symptoms and higher mortality rates due to mechanisms such as cytokine storms, myocardial infarction, myocarditis, microvascular dysfunction, thrombosis, and stress cardiomyopathy. Elevated biomarkers like troponin and natriuretic peptides correlate with severe disease. Long-term cardiovascular risks for COVID-19 survivors include increased incidence of heart failure, non-ischemic cardiomyopathy, cardiac arrest, and cardiogenic shock. COVID-19 significantly impacts patients with pre-existing heart failure, leading to severe symptoms and higher mortality. Elevated cardiac biomarkers are indicators of severe disease. Acute and long-term cardiovascular complications are common, calling for ongoing research into targeted therapies and improved management strategies to better prevent, diagnose, and treat heart failure in the context of COVID-19.

Diabetes mellitus in patients with heart failure and effect modification of risk factors for short-term mortality: An observational study from the Registro Colombiano de Falla Cardíaca (RECOLFACA). / Diabetes mellitus en pacientes con insuficiencia cardiaca y modificación del efecto de los factores de riesgo de mortalidad a corto plazo: un estudio observacional del Registro Colombiano de Falla Cardíaca (RECOLFACA)

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.

Introducción. La insuficiencia cardíaca y la diabetes mellitus de tipo 2 son problemas críticos de salud pública. Objetivo. Caracterizar los factores de riesgo de mortalidad en pacientes con insuficiencia cardíaca y la diabetes mellitus de tipo 2 de un registro grande en Colombia y evaluar las posibles modificaciones del efecto de la diabetes mellitus de tipo 2 sobre otros factores de riesgo. Materiales y métodos. Se incluyeron pacientes con insuficiencia cardíaca con y sin diabetes mellitus de tipo 2, inscritos en el Registro Colombiano de Insuficiencia Cardíaca (RECOLFACA). RECOLFACA incorporó pacientes adultos con diagnóstico de insuficiencia cardíaca de 60 centros médicos de Colombia durante 2017-2019. El resultado primario fue la mortalidad por todas las causas. El análisis de supervivencia se realizó utilizando modelos ajustados de riesgos proporcionales de Cox. Resultados. Se incluyeron 2.514 pacientes, la prevalencia de diabetes mellitus de tipo 2 fue del 24,7 % (n = 620). Encontramos siete predictores independientes de mortalidad a corto plazo para la enfermedad pulmonar obstructiva crónica del grupo sin diabetes mellitus de tipo 2, el ritmo sinusal, la terapia triple, el uso de nitratos, el uso de estatinas, la anemia y la hiperpotasemia. En el grupo de diabetes mellitus de tipo 2, solo el diámetro diastólico del ventrículo izquierdo fue un predictor de mortalidad independiente (HR = 0,96; IC95 %: 0,93 - 0,98). No hubo evidencia de modificación del efecto de la diabetes mellitus de tipo 2 sobre la relación entre ningún predictor independiente y la mortalidad por todas las causas. Sin embargo, se observó una modificación significativa del efecto de la diabetes mellitus de tipo 2 entre el tabaquismo y la mortalidad. Conclusiones. Los pacientes con diabetes mellitus de tipo 2 tuvieron mayor riesgo de mortalidad. Los resultados también sugieren que el diagnóstico de diabetes mellitus de tipo 2 no modifica el efecto de los factores de riesgo independientes de mortalidad en IC evaluados. Sin embargo, la diabetes mellitus de tipo 2 modifica significativamente la relación de riesgo entre mortalidad y tabaquismo en pacientes con insuficiencia cardíaca, posiblemente debido a un efecto sinérgico negativo que resulta en lesión vascular.

Long COVID Clusters of Symptoms Persist beyond Two Years after Infection: Insights from the CARDIO COVID 20-21 Registry.

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

Pre-Existing Atrial Fibrillation in Hospitalized Patients with COVID-19: Insights from the CARDIO COVID 19-20 Registry.

Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.

Association of Abnormal Cardiac Biomarkers and Cardiovascular Complications, with Mortality in Patients with SARS-CoV-2 Infection in Latin America.

BACKGROUND: The COVID-19 pandemic has highlighted a correlation between cardiac complications and elevated cardiac biomarkers, which are linked to poorer clinical outcomes. OBJECTIVE: This study aims to determine the clinical impact of cardiac biomarkers in COVID-19 patients in Latin America. SUBJECTS AND METHODS: The CARDIO COVID 19-20 Registry is a multicenter observational study across 44 hospitals in Latin America and the Caribbean. It included hospitalized COVID-19 patients (n = 476) who underwent troponin, natriuretic peptide, and D-dimer tests. Patients were grouped based on the number of positive biomarkers. RESULTS: Among the 476 patients tested, 139 had one positive biomarker (Group C), 190 had two (Group B), 118 had three (Group A), and 29 had none (Group D). A directly proportional relationship was observed between the number of positive biomarkers and the incidence of decompensated heart failure. Similarly, there was a proportional relationship between the number of positive biomarkers and increased mortality. In Group B, patients with elevated troponin and natriuretic peptide and those with elevated troponin and D-dimer had 1.4 and 1.5 times higher mortality, respectively, than those with elevated natriuretic peptide and D-dimer. CONCLUSIONS: In Latin American COVID-19 patients, a higher number of positive cardiac biomarkers is associated with increased cardiovascular complications and mortality. These findings suggest that cardiac biomarkers should be utilized to guide acute-phase treatment strategies.

When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Eligibility of sodium-glucose cotransporter-2 inhibitors in heart failure with preserved ejection fraction: Insights from the Colombian heart failure registry (RECOLFACA).

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 < 20 ml/min/1.73 m2 (4.3 %), and haemoglobin < 9 g/dl (3.1 %). Excluding NT-proBNP criteria increased empagliflozin eligibility to 80.6 %. Conclusion: Most patients with HFpEF from RECOLFACA are potential candidates for empagliflozin therapy initiation according to the EMPEROR-Preserved trial criteria. These findings favor the utilization of SGLT-2 inhibitor medications in daily medical practice, which may further decrease morbidity and mortality in HF patients, regardless of their EF classification.

American registry of ambulatory and acute decompensated heart failure (AMERICCAASS registry): Rationale and design.

AIMS: Heart failure (HF) is a highly prevalent and progressive condition associated with significant morbidity and mortality rates. Acute decompensated HF precipitates millions of hospitalizations each year. Despite therapeutic advances, the overall prognosis of HF is poor. The varying clinical courses and outcomes of patients with this disease may be due to region-specific gaps and since most HF studies are conducted in developed countries, the participation of Latin American and Caribbean countries is low. Considering this, the American Registry of Ambulatory and Acute Decompensated Heart Failure (AMERICCAASS) aims to characterize the population with ambulatory and acute decompensated HF in the American continent and to determine rehospitalization and survival outcomes during the 12 months of follow-up. METHODS AND RESULTS: AMERICCAASS Registry is an observational, prospective, and hospital-based registry recruiting patients with ambulatory or acute decompensated HF. The registry plans to include between two and four institutions per country from at least 20 countries in the Americas, and at least 60 patients recruited from each participant institution regardless of their ambulatory or acutely decompensated condition. Ambulatory patients with confirmed HF diagnosis or inpatients presenting with acute decompensated HF will be included. Follow-up will be performed at 12 months in ambulatory patients or 1, 6, and 12 months after hospital discharge in acutely decompensated HF patients. This ongoing study began on 1 April 2022, with recruitment scheduled to end on 30 November 2023, and follow-up on 31 January 2025. Ethics approval was obtained from the Biomedical Research Ethics Committee of Fundación Valle del Lili. Data collected in the AMERICCAASS registry is being stored on the electronic platform REDCap (Research Electronic Data Capture), which allows different forms for patient groups to enable unbiased analyses. For quantitative variables comparison, we will use the Student's t-test or non-parametric tests accordingly. Categorical variables will be presented as proportions, and groups will be compared with Fisher's exact test. The significance level will be <0.05 for comparisons. Readmissions and post-discharge mortality will be calculated as proportions at 1, 6, and 12 months, with a survival analysis by conditional probability and the Kaplan-Meier method. CONCLUSIONS: AMERICCAASS Registry is intended to be the most important registry of the continent for obtaining important information about demographics, aetiology, co-morbidities, and treatment received, either ambulatory or hospitalized. This registry may contribute to the optimization of national and regional evidence and public policies for the diagnosis and treatment of HF disease.

Risk of corrected QT interval prolongation in patients receiving antipsychotics.

Antipsychotic (AP) use has been associated to QT interval prolongation on the surface electrocardiogram (ECG). Our study aimed to determine the incidence of corrected QT (QTc) interval prolongation among patients admitted to a psychiatric hospitalization unit requiring AP treatment and to assess the relationship between administered dose and QTc interval changes. We enrolled 179 patients admitted to the Hospital Psiquiátrico Departamental Universitario del Valle in Cali, Colombia. ECGs were conducted upon admission, and again at 3 and 7 days postadmission. The QT interval was measured, and QTc interval correction was performed using Bazzet's formula. QTc interval prolongation at time points B or C was observed in 9.5% of patients. Clozapine was the most common AP associated with QTc interval prolongation (20.59%), followed by olanzapine (15.38%). The relative risk of QT interval prolongation with clozapine compared to haloperidol was 4.17 (95% confidence interval, 1.14-15.17, P = 0.02). AP use upon hospital admission was linked to early (within 3 days) QTc interval prolongation. Clozapine and olanzapine were associated with a greater increase in QTc interval compared to haloperidol, indicating a need for rigorous electrocardiographic monitoring with their use.

COATi: Statistical Pairwise Alignment of Protein-Coding Sequences.

Sequence alignment is an essential method in bioinformatics and the basis of many analyses, including phylogenetic inference, ancestral sequence reconstruction, and gene annotation. Sequencing artifacts and errors made during genome assembly, such as abiological frameshifts and incorrect early stop codons, can impact downstream analyses leading to erroneous conclusions in comparative and functional genomic studies. More significantly, while indels can occur both within and between codons in natural sequences, most amino-acid- and codon-based aligners assume that indels only occur between codons. This mismatch between biology and alignment algorithms produces suboptimal alignments and errors in downstream analyses. To address these issues, we present COATi, a statistical, codon-aware pairwise aligner that supports complex insertion-deletion models and can handle artifacts present in genomic data. COATi allows users to reduce the amount of discarded data while generating more accurate sequence alignments. COATi can infer indels both within and between codons, leading to improved sequence alignments. We applied COATi to a dataset containing orthologous protein-coding sequences from humans and gorillas and conclude that 41% of indels occurred between codons, agreeing with previous work in other species. We also applied COATi to semiempirical benchmark alignments and find that it outperforms several popular alignment programs on several measures of alignment quality and accuracy.

Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.

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.

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 (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed 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) medication 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 2,528 patients in the registry, 1,384 (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 are suboptimal 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.

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.