Primary results of the brazilian registry of atherothrombotic disease (NEAT).

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease.ClinicalTrials.gov NCT04677725.

Identification of apob variants in samples from the brazilian population with hypercholesterolemic phenotype

INTRODUCTION AND OBJECTIVES: Apolipoprotein B plays a crucial role in regulating plasma cholesterol by mediating the interaction of low-density lipoprotein (LDL) with LDL receptors in the liver. Inherited mutations in this gene may increase the risk of developing premature atherosclerotic cardiovascular disease, especially in individuals with familial hypercholesterolemia type 2 (FH2). The aim of this study is to identify APOB variants that may indicate pathogenicity in a sample of the Brazilian population using a data bank exome sequencing study by NGS in a Brazilian population phenotypically diagnosed by clinical and laboratory profile. This finding is going to improve genetic hypercholesteremia diagnosis. Casuistic, Material and METHODS: High quality DNA samples (n=300) were sequenced using an exon- targeted gene sequencing (ETGS) strategy to identify variants in FH-related genes. Pathogenicity classification was based on criteria established by the American College of Medical Genetics and Genomics (ACMG), also using information from ClinVar and pathogenicity scores from previous association studies. RESULTS and CONCLUSIONS: A total of 121 variants were identified in APOB, of which four are novel variants missense (p.Thr626Asn, p.Ile2750Thr, p.Gln2078Lys and p.Met4184Arg). After curating pathogenicity scores, variants were classified according to the ACMG criteria. Among them four as pathogenic or likely pathogenic (p.Pro2739Leu, p.His1923Arg, p.Pro994Leu and p.Pro877Leu), and 21 variants had uncertain significance. Additionally, 92 previously known variants with uncertain significance were classified as benign or likely benign. The results were submitted to Clinvar for actualization of pathogenicity and to improve the molecular diagnosis associating APOB variants with the clinical phenotype of hypercholesterolemia. Financing: FAPESP, CNPQ, CAPES.

Identification of pathogenic variants in the brazilian cohort with familial hypercholesterolemia using exon-targeted gene sequencing

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows-Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Toolkit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regulatory regions (3'UTR and 5'UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown uncertain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows-Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Toolkit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regulatory regions (3'UTR and 5'UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown uncertain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

Cardiac Surgery-associated Acute Kidney Injury in Patients with Preserved Baseline Renal Function.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a powerful predictor of perioperative outcomes. We evaluated the burden of CSA-AKI in patients with preserved baseline renal function. METHODS: The data of 2,162 adult patients who underwent cardiac surgery from January 2005 to December 2020 were analyzed. Logistic regression models were used to determine predictors of CSA-AKI and their associations with hospital mortality up to 30 days. RESULTS: The prevalence of acute kidney injury was 43.0%, and 2.0% of patients required renal replacement therapy. Hospital mortality rate was 5.6% (non-acute kidney injury = 2.0% vs. CSA-AKI = 10.4%, P<0.001), and any degree of CSA-AKI was associated with a significant increase in death rates (stage 1 = 4.3%, stage 2 = 23.9%, stage 3 = 59.7%). Multivariable logistic regression analysis identified age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration as predictors of CSA-AKI. Moreover, CSA-AKI was confirmed as independent predictor of hospital mortality for stage 1 (odds ratio, 2.02; 95% confidence interval, 1.16 to 3.51; P=0.013), stage 2 (odds ratio, 9.18; 95% confidence interval, 4.54 to 18.58; P<0.001), and stage 3 (odds ratio, 37.72; 95% confidence interval, 18.87 to 75.40; P<0.001) patients. CONCLUSION: Age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration are independent predictors of CSA-AKI in patients with preserved baseline renal function. The development of CSA-AKI is significantly associated with worse outcomes, and there is a dose-response relationship between acute kidney injury stages and hospital mortality.

Cardiac Surgery-associated Acute Kidney Injury in Patients with Preserved Baseline Renal Function

ABSTRACT Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a powerful predictor of perioperative outcomes. We evaluated the burden of CSA-AKI in patients with preserved baseline renal function. Methods: The data of 2,162 adult patients who underwent cardiac surgery from January 2005 to December 2020 were analyzed. Logistic regression models were used to determine predictors of CSA-AKI and their associations with hospital mortality up to 30 days. Results: The prevalence of acute kidney injury was 43.0%, and 2.0% of patients required renal replacement therapy. Hospital mortality rate was 5.6% (non-acute kidney injury = 2.0% vs. CSA-AKI = 10.4%, P<0.001), and any degree of CSA-AKI was associated with a significant increase in death rates (stage 1 = 4.3%, stage 2 = 23.9%, stage 3 = 59.7%). Multivariable logistic regression analysis identified age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration as predictors of CSA-AKI. Moreover, CSA-AKI was confirmed as independent predictor of hospital mortality for stage 1 (odds ratio, 2.02; 95% confidence interval, 1.16 to 3.51; P=0.013), stage 2 (odds ratio, 9.18; 95% confidence interval, 4.54 to 18.58; P<0.001), and stage 3 (odds ratio, 37.72; 95% confidence interval, 18.87 to 75.40; P<0.001) patients. Conclusion: Age, obesity, left ventricular dysfunction, previous cardiac surgery, and cardiopulmonary bypass duration are independent predictors of CSA-AKI in patients with preserved baseline renal function. The development of CSA-AKI is significantly associated with worse outcomes, and there is a dose-response relationship between acute kidney injury stages and hospital mortality.

Performance of a novel risk model for deep sternal wound infection after coronary artery bypass grafting.

Clinical prediction models for deep sternal wound infections (DSWI) after coronary artery bypass graft (CABG) surgery exist, although they have a poor impact in external validation studies. We developed and validated a new predictive model for 30-day DSWI after CABG (REPINF) and compared it with the Society of Thoracic Surgeons model (STS). The REPINF model was created through a multicenter cohort of adults undergoing CABG surgery (REPLICCAR II Study) database, using least absolute shrinkage and selection operator (LASSO) logistic regression, internally and externally validated comparing discrimination, calibration in-the-large (CL), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), trained between the new model and the STS PredDeep, a validated model for DSWI after cardiac surgery. In the validation data, c-index = 0.83 (95% CI 0.72-0.95). Compared to the STS PredDeep, predictions improved by 6.5% (IDI). However, both STS and REPINF had limited calibration. Different populations require independent scoring systems to achieve the best predictive effect. The external validation of REPINF across multiple centers is an important quality improvement tool to generalize the model and to guide healthcare professionals in the prevention of DSWI after CABG surgery.

Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger.

Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.

Does left ventricular reverse remodeling influence long-term outcomes in patients with Chagas cardiomyopathy?

BACKGROUND: The impact of left ventricular reverse remodeling (LVRR) on the prognosis of Chagas cardiomyopathy is unknown. The aim of this study was to determine whether the presence of LVRR can predict mortality in these patients. METHODS: From January 2000 to December 2010, the medical charts of 159 patients were reviewed. LVRR was defined as an increase of left ventricular ejection fraction (LVEF) and a decrease of left ventricular end-diastolic diameter (LVDD) by two-dimensional echocardiography. No patient underwent cardiac resynchronization therapy or required mechanical ventricular assistance. RESULTS: At baseline, median (25th-75th) LVDD was 64 mm (59-70), and median LVEF was 33.2% (26.4-40.1). LVRR was detected in 24.5% of patients in a 40-month (26-64) median follow-up. In the LVRR group, LVDD decreased from 64 mm (59-68) to 60 mm (56-65; p < 0.001), and LVEF increased from 31.3% (24.1-39.0) to 42.5% (32.2-47.7; p < 0.001). However, LVRR was not associated with heart failure hospitalization, cardiogenic shock, heart transplantation, or mortality (p > 0.05 for all comparisons). The Cox proportional hazard model analysis identified only cardiogenic shock (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 1.51-3.85; p < 0.001) and serum sodium level (HR: 0.91; 95% CI: 0.86-0.96; p < 0.001) as independent predictors of all-cause mortality. CONCLUSIONS: Left ventricular reverse remodeling occurs in one quarter of patients with Chagas cardiomyopathy and have no impact on the outcomes of patients with this condition.

Correction: Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

[This corrects the article DOI: 10.1371/journal.pone.0255662.].

Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

BACKGROUND: The performance of traditional scores is significantly limited to predict mortality in high-risk cardiac surgery. The aim of this study was to compare the performance of STS, ESII and HiriSCORE models in predicting mortality in high-risk patients undergoing CABG. METHODS: Cross-sectional analysis in the international prospective database of high-risk patients: HiriSCORE project. We evaluated 248 patients with STS or ESII (5-10%) undergoing CABG in 8 hospitals in Brazil and China. The main outcome was mortality, defined as all deaths occurred during the hospitalization in which the operation was performed, even after 30 days. Five variables were selected as predictors of mortality in this cohort of patients. The model's performance was evaluated through the calibration-in-the-large and the receiver operating curve (ROC) tests. RESULTS: The mean age was 69.90±9.45, with 52.02% being female, 25% of the patients were on New York Heart Association (NYHA) class IV and 49.6% had Canadian Cardiovascular Society (CCS) class 4 angina, and 85.5% had urgency or emergency status. The mortality observed in the sample was 13.31%. The HiriSCORE model showed better calibration (15.0%) compared to ESII (6.6%) and the STS model (2.0%). In the ROC curve, the HiriSCORE model showed better accuracy (ROC = 0.74) than the traditional models STS (ROC = 0.67) and ESII (ROC = 0.50). CONCLUSION: Traditional models were inadequate to predict mortality of high-risk patients undergoing CABG. However, the HiriSCORE model was simple and accurate to predict mortality in high-risk patients.

Genomics, epigenomics and pharmacogenomics of Familial Hypercholesterolemia (FHBGEP): A study protocol

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. SUMMARY: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients.

Most deaths in low-risk cardiac surgery could be avoidable.

It is observed that death rates in cardiac surgery has decreased, however, root causes that behave like triggers of potentially avoidable deaths (AD), especially in low-risk patients (less bias) are often unknown and underexplored, Phase of Care Mortality Analysis (POCMA) can be a valuable tool to identify seminal events (SE), providing valuable information where it is possible to make improvements in the quality and safety of future procedures. Our results show that in São Paul State, only one third of AD in low-risk cardiac surgery was related to specific surgical problems. After a revisited analysis, 75% of deaths could have been avoided, which in the pre-operative phase, the SE was related judgment, patient evaluation and preparation. In the intra-operative phase, most occurrences could have been avoided if other surgical technique had been used. Sepsis was responsible for 75% of AD in the intensive care unit. In the ward phase, the recognition/management of clinical decompensations and sepsis were the contributing factors. Logistic regression model identified age, previous coronary stent implantation, coronary artery bypass grafting + heart valve surgery, ≥ 2 combined heart valve surgery and hospital-acquired infection as independent predictors of AD.

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. SUMMARY: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients.

Validation and quality measurements for STS, EuroSCORE II and a regional risk model in Brazilian patients.

OBJECTIVES: The objectives of this study were to describe a novel statewide registry for cardiac surgery in Brazil (REPLICCAR), to compare a regional risk model (SPScore) with EuroSCORE II and STS, and to understand where quality improvement and safety initiatives can be implemented. METHODS: A total of 11 sites in the state of São Paulo, Brazil, formed an online registry platform to capture information on risk factors and outcomes after cardiac surgery procedures for all consecutive patients. EuroSCORE II and STS values were calculated for each patient. An SPScore model was designed and compared with EuroSCORE II and STS to predict 30-day outcomes: death, reoperation, readmission, and any morbidity. RESULTS: A total of 5222 patients were enrolled in this study between November 2013 and December 2017. The observed 30-day mortality rate was 7.6%. Most patients were older, overweight, and classified as New York Heart Association (NYHA) functional class III; 14.5% of the patient population had a positive diagnosis of rheumatic heart disease, 10.9% had insulin-dependent diabetes, and 19 individuals had a positive diagnosis of Chagas disease. When evaluating the prediction performance, we found that SPScore outperformed EuroSCORE II and STS in the prediction of mortality (0.90 vs. 0.76 and 0.77), reoperation (0.84 vs. 0.60 and 0.56), readmission (0.84 vs. 0.55 and 0.51), and any morbidity (0.80 vs. 0.65 and 0.64), respectively (p<0.001). CONCLUSIONS: The REPLICCAR registry might stimulate the creation of other cardiac surgery registries in developing countries, ultimately improving the regional quality of care provided to patients.

REPLICCAR II Study: Data quality audit in the Paulista Cardiovascular Surgery Registry.

The quality of data in electronic healthcare databases is a critical component when used for research and health practice. The aim of the present study was to assess the data quality in the Paulista Cardiovascular Surgery Registry II (REPLICCAR II) using two different audit methods, direct and indirect. The REPLICCAR II database contains data from 9 hospitals in São Paulo State with over 700 variables for 2229 surgical patients. The data collection was performed in REDCap platform using trained data managers to abstract information. We directly audited a random sample (n = 107) of the data collected after 6 months and indirectly audited the entire sample after 1 year of data collection. The indirect audit was performed using the data management tools in REDCap platform. We computed a modified Aggregate Data Quality Score (ADQ) previously reported by Salati et al. (2015). The agreement between data elements was good for categorical data (Cohen κ = 0.7, 95%CI = 0.59-0.83). For continuous data, the intraclass coefficient (ICC) for only 2 out of 15 continuous variables had an ICC < 0.9. In the indirect audit, 77% of the selected variables (n = 23) had a good ADQ score for completeness and accuracy. Data entry in the REPLICCAR II database proved to be satisfactory and showed competence and reliable data for research in cardiovascular surgery in Brazil.

Prognostic Significance of Chronic Kidney Disease (CKD-EPI Equation) and Anemia in Patients with Chronic Heart Failure Secondary to Chagas Cardiomyopathy.

BACKGROUND: Few studies regarding chronic kidney disease (CKD) and anemia have been conducted in patients with Chagas cardiomyopathy (CC). We evaluated the risk prediction performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and anemia in CC patients. METHODS: From 2000 to 2010, a total of 232 patients were studied in a single-center retrospective study. CKD was defined as creatinine clearance <60 mL/min/1.73 m2 according to CKD-EPI equation. Anemia was defined as hemoglobin <12 g/dL (women) and <13 g/dL (men). Cox proportional hazards models were used to establish predictors for death. RESULTS: At baseline, 98 individuals (42.2%) had criteria for CKD and 41 (17.7%) for anemia. During follow-up, 136 patients (58.6%) died. Independently, CKD and anemia were not associated with all-cause mortality. However, when they coexisted, an additional risk was attributed for these patients. Cox proportional hazard models analysis identified systolic blood pressure (hazard ratio, 0.99; 95% confidence interval (CI), 0.98 to 1.00; P=0.015), implantable cardioverter-defibrillator (hazard ratio, 0.48; 95% CI, 0.27 to 0.85; P=0.012), left anterior fascicular block (hazard ratio, 1.52; 95% CI, 1.08 to 2.13; P=0.017), left ventricular end-diastolic diameter (hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P < 0.001), and serum sodium (hazard ratio, 0.95; 95% CI, 0.92 to 0.99; P=0.020) as independent predictors for death. CONCLUSIONS: CKD and anemia are not independent predictors for long-term mortality in CC patients. However, the prognosis is poorer in individuals with both comorbidities.

The use of the CALL Risk Score for predicting mortality in Brazilian heart failure patients.

AIMS: This study aimed to develop and validate a simple method for predicting long-term all-cause mortality in ambulatory patients with chronic heart failure (CHF) residing in an area where Chagas disease is endemic, which will be important not only for patients living in Latin America but also to those living in developed non-endemic countries. METHODS AND RESULTS: A total of 677 patients with a wide spectrum of aetiologies for left ventricular systolic dysfunction and receiving optimized evidence-based treatment for CHF were prospectively followed for approximately 11 years. We established a risk score using Cox proportional hazard regression models. After multivariable analysis, four variables were independently associated with mortality and included in the CALL Risk Score: Chagas cardiomyopathy aetiology alone [hazard ratio, 3.36; 95% confidence interval (CI), 2.61-4.33; P < 0.001], age ≥60 years (hazard ratio, 1.36; 95% CI, 1.06-1.74; P = 0.016), left anterior fascicular block (hazard ratio, 1.64; 95% CI, 1.27-2.11; P < 0.001), and left ventricular ejection fraction <40% (hazard ratio, 1.73; 95% CI, 1.30-2.28; P < 0.001). The internal validation considered the bootstrapping, a resampling technique recommended for prediction model development. Hence, we established a scoring system attributing weights according to each risk factor: 3 points for Chagas cardiomyopathy alone, 1 point for age ≥60 years, and 2 points each for left anterior fascicular block and left ventricular ejection fraction <40%. Three risk groups were identified: low risk (score ≤2 points), intermediate risk (score of 3 to 5 points), and high risk (score ≥6 points). High-risk patients had more than two-fold increase in mortality (26.9 events/100 patient-years) compared with intermediate-risk patients (10.1 events/100 patient-years) and almost seven-fold increase compared with low-risk patients (4.3 events/100 patient-years). The CALL Risk Score data sets from the development and internal validation cohorts both displayed suitable discrimination c-index of 0.689 (95% CI, 0.688-0.690; P < 0.001) and 0.687 (95% CI, 0.686-0.688; P < 0.001), respectively, and satisfactory calibration [Greenwood-Nam-D'Agostino test (8) = 7.867; P = 0.447] and [Greenwood-Nam-D'Agostino test (8) = 10.08; P = 0.273], respectively. CONCLUSIONS: The CALL Risk Score represents a simple and validated method with a limited number of non-invasive variables that successfully predicts long-term all-cause mortality in a real-world cohort of patients with CHF. Patients with CHF stratified as high risk according to the CALL Risk Score should be monitored and aggressively managed, including those with CHF secondary to Chagas disease.