Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study.

BACKGROUND AND OBJECTIVE: AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. METHODS: 359 subjects aged 65-75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (NuuboTM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. RESULTS: AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780-1]), while MyDiagnostick showed the highest specificity (97.10%). CONCLUSION: The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible.

Burden of heart failure in primary healthcare / Impacto de la insuficiencia cardíaca en la atención primaria

Objectives: To determine the epidemiology of heart failure registered in primary healthcare clinical records in Catalunya, Spain, between 2010 and 2014, focusing on incidence, mortality, and resource utilization. Design: Retrospective observational cohort study. Setting: Study was carried out in primary care setting. Participants and interventions: Patients registered as presenting a new heart failure diagnosis. The inclusion period ran from 1st January 2010 to 31st December 2013, but patients were followed until 31st December 2013 in order to analyze mortality. Main measures: Information came from electronic medical records. Results: A total of 64441 patients were registered with a new diagnosis of heart failure (2.76 new cases per 1000 persons-year). Among them, 85.8% were ≥65 years. The number of cases/1000 persons-year was higher in men in all age groups. Incidence ranged from 0.04 in women <45 years to 27.61 in the oldest group, and from 0.08 in men <45 years to 28.52 in the oldest group. Mortality occurred in 16305 (25.3%) patients. Primary healthcare resource utilization increased after the occurrence of heart failure, especially the number of visits made by nurses to the patients’ homes. Conclusion: Heart failure incidence increases with age, is greater in men, and remains stable. Mortality continues to be high in newly diagnosed patients in spite of the current improvements in treatment. Home visits represent the greatest cost for the management of this disease in primary care setting.(AU)

Objetivo: Determinar la epidemiología de la insuficiencia cardíaca registrada en las historias clínicas de atención primaria en Cataluña, España, entre 2010 y 2014, centrándose en la incidencia, la mortalidad y la utilización de recursos sanitarios. Diseño: Estudio de cohorte observacional retrospectivo. Emplazamiento: El estudio se llevó a cabo en atención primaria. Participantes e intervenciones: Pacientes registrados con nuevo diagnóstico de insuficiencia cardíaca en el período de estudio. El período de inclusión fue del 1 de enero de 2010 al 31 de diciembre de 2013, pero los pacientes se siguieron hasta el 31 de diciembre de 2014 para poder determinar la mortalidad. Mediciones principales: La información se obtuvo de la historia clínica electrónica de los participantes. Resultados: Se registraron un total de 64.441 pacientes con nuevo diagnóstico de insuficiencia cardíaca (2,76 nuevos casos/1000 personas-año). De ellos, el 85,8% tenían ≥65 años. El número de casos/1000 personas-año fue mayor en hombres en todos los grupos de edad. La incidencia varió de 0,04 en mujeres <45 años a 27,61 en el grupo de mayor edad, y de 0,08 en hombres <45 años a 28,52 en el grupo de mayor edad. La mortalidad se produjo en 16.305 (25,3%) pacientes. La utilización de los recursos de atención primaria aumentó tras el diagnóstico de insuficiencia cardíaca, especialmente el número de visitas realizadas por las enfermeras a los pacientes en su domicilio. Conclusión: La incidencia de insuficiencia cardíaca aumenta con la edad, es mayor en hombres y se mantiene estable en el tiempo. La mortalidad continúa siendo alta en pacientes recién diagnosticados a pesar de las mejoras actuales en el tratamiento. Las visitas domiciliarias representan el mayor coste para el manejo de esta enfermedad en el ámbito de atención primaria.(AU)

Burden of heart failure in primary healthcare.

OBJECTIVES: To determine the epidemiology of heart failure registered in primary healthcare clinical records in Catalunya, Spain, between 2010 and 2014, focusing on incidence, mortality, and resource utilization. DESIGN: Retrospective observational cohort study. SETTING: Study was carried out in primary care setting. PARTICIPANTS AND INTERVENTIONS: Patients registered as presenting a new heart failure diagnosis. The inclusion period ran from 1st January 2010 to 31st December 2013, but patients were followed until 31st December 2013 in order to analyze mortality. MAIN MEASURES: Information came from electronic medical records. RESULTS: A total of 64441 patients were registered with a new diagnosis of heart failure (2.76 new cases per 1000 persons-year). Among them, 85.8% were ≥65 years. The number of cases/1000 persons-year was higher in men in all age groups. Incidence ranged from 0.04 in women <45 years to 27.61 in the oldest group, and from 0.08 in men <45 years to 28.52 in the oldest group. Mortality occurred in 16305 (25.3%) patients. Primary healthcare resource utilization increased after the occurrence of heart failure, especially the number of visits made by nurses to the patients' homes. CONCLUSION: Heart failure incidence increases with age, is greater in men, and remains stable. Mortality continues to be high in newly diagnosed patients in spite of the current improvements in treatment. Home visits represent the greatest cost for the management of this disease in primary care setting.

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients.

Background: Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. Methods: Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. Results: Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. Conclusion: Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Predictive model for atrial fibrillation in hypertensive diabetic patients.

BACKGROUND: Several scores to identify patients at high risk of suffering atrial fibrillation have been developed. Their applicability in hypertensive diabetic patients, however, remains uncertain. Our aim is to develop and validate a diagnostic predictive model to calculate the risk of developing atrial fibrillation at five years in a hypertensive diabetic population. METHODS: The derivation cohort consisted of patients with both hypertension and diabetes attended in any of the 52 primary healthcare centres of Barcelona; the validation cohort came from the 11 primary healthcare centres of Terres de l'Ebre (Catalonia South) from January 2013 to December 2017. Multivariable Cox regression identified clinical risk factors associated with the development of atrial fibrillation. The overall performance, discrimination and calibration of the model were carried out. RESULTS: The derivation data set comprised 54 575 patients. The atrial fibrillation rate incidence was 15.3 per 1000 person/year. A 5-year predictive model included age, male gender, overweight, heart failure, valvular heart disease, peripheral vascular disease, chronic kidney disease, number of antihypertensive drugs, systolic and diastolic blood pressure, heart rate, thromboembolism, stroke and previous history of myocardial infarction. The discrimination of the model was good (c-index = 0.692; 95% confidence interval, 0.684-0.700), and calibration was adequate. In the validation cohort, the discrimination was lower (c-index = 0.670). CONCLUSIONS: The model accurately predicts future atrial fibrillation in a population with both diabetes and hypertension. Early detection allows the prevention of possible complications arising from this disease.

N-Terminal Pro B-Type Natriuretic Peptide's Usefulness for Paroxysmal Atrial Fibrillation Detection Among Populations Carrying Cardiovascular Risk Factors.

Background: Atrial fibrillation (AF) systematic screening studies have not shown a clear usefulness in stroke prevention, as AF might present as paroxysmal and asymptomatic. This study aims to determine the usefulness of some blood-biomarkers to identify paroxysmal atrial fibrillation in the context of a screening programme. Methods: A total of 100 subjects aged 65-75 years with hypertension and diabetes were randomly selected. AF was assessed by conventional electrocardiogram (ECG) and 4 weeks monitoring with a wearable Holter device (Nuubo™). N-terminal pro B-type natriuretic peptide (NT-proBNP), apolipoprotein CIII (ApoC-III), von Willebrand factor (vWF), ADAMTS13, urokinase plasminogen activator surface receptor (uPAR), and urokinase plasminogen activator (uPA) were determined in serum/plasma samples and the levels were compared depending on AF presence and mode of detection. Results: The AF prevalence in the studied population was found to be 20%. In seven subjects, AF was only detected after 1 month of Holter monitoring (hAF group). NT-proBNP levels were higher in subjects with AF compared with subjects with no AF (p < 0.0001), even when only taking into account the hAF group (p = 0.031). No significant differences were found in the other biomarkers. The NT-proBNP >95 pg/ml cut-off showed high sensitivity and specificity to detect AF (95%, 66.2%) or hAF (85.72%, 66.2%) and was found to be an independent predictor of AF and hAF in a logistic regression analysis. NT-proBNP correlated with AF burden (r = 0.597, p = 0.024). Conclusion: NT-proBNP was elevated in AF cases not identified by ECG; thus, it may be used as a screening biomarker in asymptomatic high-risk populations, with a promising cut-off point of 95 pg/ml that requires further validation.

Mortality in heart failure with atrial fibrillation: Role of digoxin and diuretics.

BACKGROUND: The impact of atrial fibrillation (AF) on mortality of patients with heart failure (HF) has been established. Nevertheless, the effect of some factors in mortality, such as digoxin or diuretic use, remains controversial. This study aims at assessing mortality in community-dwelling patients with stable HF related to AF and determines the relation of these drugs with prognosis. MATERIALS AND METHODS: Community-based cohort study of HF patients diagnosed between January 2010 and December 2014 attended at any one of the 279 primary healthcare centres of the Catalan Institute of Health (Spain). Follow-up ended on December 31, 2015, and the main outcome was mortality for all causes. The effect of clinical and demographic characteristics on survival was assessed by Cox proportional hazards model. RESULTS: A total of 13 334 HF patients were included. Mean age was 78.7 years (SD 10.1), and 36.8% had AF. Mean follow-up was 26.9 months (SD 14.0). At the end of the study, 25.8% patients had died, and mortality was higher when AF was present (28.8% vs 24.1%, P < 0.001, respectively). Multivariate model confirmed the higher risk of death for AF patients (HR 1.10 95%, CI 1.02-1.19). Digoxin and diuretics were not associated with higher mortality in AF patients (HR 1.04 95% CI 0.92-1.18 and HR 1.04 95% CI 0.85-1.26, respectively). CONCLUSIONS: An excess of mortality in HF patients with AF was found in a large retrospective community-based cohort. Digoxin and diuretics did not affect mortality in HF patients with AF.