Associação entre Bloqueio Atrioventricular e Mortalidade em Pacientes de Atenção Primária: O Estudo CODE / Association between Atrioventricular Block and Mortality in Primary Care Patients: The CODE Study

Resumo Fundamento O bloqueio atrioventricular (BAV) descreve um comprometimento na condução dos átrios para os ventrículos. Embora o curso clínico do BAV tenha sido avaliado, os achados são de países de alta renda e, portanto, não podem ser extrapolados para a população latina. Objetivo Avaliar a associação entre BAV e mortalidade. Métodos Foram incluídos pacientes do estudo CODE (Clinical Outcomes in Digital Electrocardiology), maiores de 16 anos que realizaram eletrocardiograma (ECG) digital de 2010 a 2017. Os ECGs foram relatados por cardiologistas e por software automatizado. Para avaliar a relação entre BAV e mortalidade, foram utilizados o modelo log-normal e as curvas de Kaplan-Meier com valores de p bicaudais < 0,05 considerados estatisticamente significativos. Resultados O estudo incluiu 1.557.901 pacientes; 40,23% eram homens e a média de idade foi de 51,7 (DP ± 17,6) anos. Durante um seguimento médio de 3,7 anos, a mortalidade foi de 3,35%. A prevalência de BAV foi de 1,38% (21.538). Os pacientes com BAV de primeiro, segundo e terceiro graus foram associados a uma taxa de sobrevida 24% (taxa de sobrevida relativa [RS] = 0,76; intervalo de confiança [IC] de 95%: 0,71 a 0,81; p < 0,001), 55% (RS = 0,45; IC de 95%: 0,27 a 0,77; p = 0,01) e 64% (RS = 0,36; IC de 95%: 0,26 a 0,49; p < 0,001) menor quando comparados ao grupo controle, respectivamente. Os pacientes com BAV 2:1 tiveram 79% (RS = 0,21; IC de 95%: 0,08 a 0,52; p = 0,005) menor taxa de sobrevida do que o grupo controle. Apenas Mobitz tipo I não foi associado a maior mortalidade (p = 0,27). Conclusão BAV foi um fator de risco independente para mortalidade geral, com exceção do BAV Mobitz tipo I.

Abstract Background Atrioventricular block (AVB) describes an impairment of conduction from the atria to the ventricles. Although the clinical course of AVB has been evaluated, the findings are from high-income countries and, therefore, cannot be extrapolated to the Latinx population. Objective Evaluate the association between AVB and mortality. Methods Patients from the CODE (Clinical Outcomes in Digital Electrocardiology) study, older than 16 years who underwent digital electrocardiogram (ECG) from 2010 to 2017 were included. ECGs were reported by cardiologists and by automated software. To assess the relationship between AVB and mortality, the log-normal model and the Kaplan-Meier curves were used with two-tailed p-values < 0.05 considered statistically significant. Results The study included 1,557,901 patients; 40.2% were men, and mean age was 51.7 (standard deviation ± 17.6) years. In a mean follow-up of 3.7 years, the mortality rate was 3.35%. The AVB prevalence was 1.38% (21,538). Patients with first-, second-, and third-degree AVB were associated with 24% (relative survival rate [RS] = 0.76; 95% confidence interval [CI]: 0.71-0.81; p < 0.001), 55% (RS = 0.45; 95% CI: 0.27-0.77; p = 0.01), and 64% (RS = 0.36; 95% CI: 0.26-0.49; p < 0.001) lower survival rate when compared to the control group, respectively. Patients with 2:1 AVB had 79% (RS = 0.21; 95% CI: 0.08-0.52; p = 0.005) lower survival rate than the control group. Only Mobitz type I was not associated with higher mortality (p = 0.27). Conclusion AVB was an independent risk factor for overall mortality, with the exception of Mobitz type I.

Association between Atrioventricular Block and Mortality in Primary Care Patients: The CODE Study. / Associação entre Bloqueio Atrioventricular e Mortalidade em Pacientes de Atenção Primária: O Estudo CODE.

BACKGROUND: Atrioventricular block (AVB) describes an impairment of conduction from the atria to the ventricles. Although the clinical course of AVB has been evaluated, the findings are from high-income countries and, therefore, cannot be extrapolated to the Latinx population. OBJECTIVE: Evaluate the association between AVB and mortality. METHODS: Patients from the CODE (Clinical Outcomes in Digital Electrocardiology) study, older than 16 years who underwent digital electrocardiogram (ECG) from 2010 to 2017 were included. ECGs were reported by cardiologists and by automated software. To assess the relationship between AVB and mortality, the log-normal model and the Kaplan-Meier curves were used with two-tailed p-values < 0.05 considered statistically significant. RESULTS: The study included 1,557,901 patients; 40.2% were men, and mean age was 51.7 (standard deviation ± 17.6) years. In a mean follow-up of 3.7 years, the mortality rate was 3.35%. The AVB prevalence was 1.38% (21,538). Patients with first-, second-, and third-degree AVB were associated with 24% (relative survival rate [RS] = 0.76; 95% confidence interval [CI]: 0.71-0.81; p < 0.001), 55% (RS = 0.45; 95% CI: 0.27-0.77; p = 0.01), and 64% (RS = 0.36; 95% CI: 0.26-0.49; p < 0.001) lower survival rate when compared to the control group, respectively. Patients with 2:1 AVB had 79% (RS = 0.21; 95% CI: 0.08-0.52; p = 0.005) lower survival rate than the control group. Only Mobitz type I was not associated with higher mortality (p = 0.27). CONCLUSION: AVB was an independent risk factor for overall mortality, with the exception of Mobitz type I.

FUNDAMENTO: O bloqueio atrioventricular (BAV) descreve um comprometimento na condução dos átrios para os ventrículos. Embora o curso clínico do BAV tenha sido avaliado, os achados são de países de alta renda e, portanto, não podem ser extrapolados para a população latina. OBJETIVO: Avaliar a associação entre BAV e mortalidade. MÉTODOS: Foram incluídos pacientes do estudo CODE (Clinical Outcomes in Digital Electrocardiology), maiores de 16 anos que realizaram eletrocardiograma (ECG) digital de 2010 a 2017. Os ECGs foram relatados por cardiologistas e por software automatizado. Para avaliar a relação entre BAV e mortalidade, foram utilizados o modelo log-normal e as curvas de Kaplan-Meier com valores de p bicaudais < 0,05 considerados estatisticamente significativos. RESULTADOS: O estudo incluiu 1.557.901 pacientes; 40,23% eram homens e a média de idade foi de 51,7 (DP ± 17,6) anos. Durante um seguimento médio de 3,7 anos, a mortalidade foi de 3,35%. A prevalência de BAV foi de 1,38% (21.538). Os pacientes com BAV de primeiro, segundo e terceiro graus foram associados a uma taxa de sobrevida 24% (taxa de sobrevida relativa [RS] = 0,76; intervalo de confiança [IC] de 95%: 0,71 a 0,81; p < 0,001), 55% (RS = 0,45; IC de 95%: 0,27 a 0,77; p = 0,01) e 64% (RS = 0,36; IC de 95%: 0,26 a 0,49; p < 0,001) menor quando comparados ao grupo controle, respectivamente. Os pacientes com BAV 2:1 tiveram 79% (RS = 0,21; IC de 95%: 0,08 a 0,52; p = 0,005) menor taxa de sobrevida do que o grupo controle. Apenas Mobitz tipo I não foi associado a maior mortalidade (p = 0,27). CONCLUSÃO: BAV foi um fator de risco independente para mortalidade geral, com exceção do BAV Mobitz tipo I.

Deep neural network-estimated electrocardiographic age as a mortality predictor.

The electrocardiogram (ECG) is the most commonly used exam for the evaluation of cardiovascular diseases. Here we propose that the age predicted by artificial intelligence (AI) from the raw ECG (ECG-age) can be a measure of cardiovascular health. A deep neural network is trained to predict a patient's age from the 12-lead ECG in the CODE study cohort (n = 1,558,415 patients). On a 15% hold-out split, patients with ECG-age more than 8 years greater than the chronological age have a higher mortality rate (hazard ratio (HR) 1.79, p < 0.001), whereas those with ECG-age more than 8 years smaller, have a lower mortality rate (HR 0.78, p < 0.001). Similar results are obtained in the external cohorts ELSA-Brasil (n = 14,236) and SaMi-Trop (n = 1,631). Moreover, even for apparent normal ECGs, the predicted ECG-age gap from the chronological age remains a statistically significant risk predictor. These results show that the AI-enabled analysis of the ECG can add prognostic information.

Ventricular pre-excitation in primary care patients: Evaluation of the risk of mortality.

BACKGROUND: Ventricular pre-excitation is characterized by the presence of atrioventricular accessory pathways, predisposing to arrhythmias. Although it is well established that risk stratification in symptomatic patients should be invasive, there is a lack of evidence of the benefit in asymptomatic. OBJECTIVE: Evaluate ventricular pre-excitation in the electrocardiogram (ECG) as a risk factor for overall mortality in patients of Telehealth Network of Minas Gerais (TNMG), Brazil. METHODS: This observational study was developed with the database of digital ECGs (2010-2017) from TNMG. The electronic cohort was obtained by linking data from ECG exams and those from the national mortality information system. Only the first ECG was considered. Clinical data were self-reported, and ECGs were interpreted manually by cardiologists and automatically by the Glasgow University Interpreter software. Hazard ratio (HR) for mortality was estimated using weighted Cox regression. RESULTS: Nearly 1 665 667 patients were included (median age: 50 [Q1: 34; Q3: 63] years; 41.4% were male). In a mean follow-up of 3.7 years, the overall mortality rate was 3.1%. The prevalence of ventricular pre-excitation was 0.07%. In multivariate analysis, adjusting for sex and age, ventricular pre-excitation was not associated with an increased risk of mortality (HR: 1.41; 95% confidence interval [CI]: 0.56-3.57; p = .47) when compared to the whole sample or to patients with normal ECG (HR: 1.41; 95% CI: 0.53-4.36; p = .43). In a subanalysis on accessory pathway location, there was no evidence of a higher risk of death related to any location. CONCLUSION: Ventricular pre-excitation was not associated with an increased risk of mortality in a primary care cohort.

Evaluation of Mortality in Atrial Fibrillation: Clinical Outcomes in Digital Electrocardiography (CODE) Study.

Aims: Atrial fibrillation (AF) is a public health problem and its prevalence is increasing worldwide. Electronic cohorts, with large electrocardiogram (ECG) databases linked to mortality data, can be useful in determining prognostic value of ECG abnormalities. Our aim is to evaluate the risk of mortality in patients with AF from Brazil. Methods: This observational retrospective study of primary care patients was developed with the digital ECG database from the Telehealth Network of Minas Gerais, Brazil. ECGs performed from 2010 to 2017 were interpreted by cardiologists and the University of Glasgow automated analysis software. An electronic cohort was obtained linking data from ECG exams and those from a national mortality information system, using standard probabilistic linkage methods. We considered only the first ECG of each patient. Patients under 16 years were excluded. Hazard ratios (HR) for mortality were adjusted for demographic and self-reported clinical factors and estimated with Cox regression. Results: From a dataset of 1,773,689 patients, 1,558,421 were included, mean age 51.6 years; 40.2% male. There were 3.34% deaths from all causes in 3.68 years of median follow up. The prevalence of AF was 1.33%. AF was an independent risk factor for all-cause mortality (HR 2.10, 95%CI 2.03-2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86-2.29). Females with AF had a higher risk of overall and cardiovascular mortality compared with males (p < 0.001). Conclusions: AF was a strong predictor of cardiovascular and all-cause mortality in a primary care population, with increased risk in women. Condensed abstract: To assess risk of mortality in AF patients, an electronic cohort was obtained linking data from ECG exams of Brazilian primary care patients and a national mortality information system. From 1,558,421 patients, AF (prevalence 1.33%) carried a higher risk of overall and cardiovascular mortality, with increased risk in women. What's New: This is the first study with a large Brazilian electronic cohort to evaluate the risk of mortality linked to AF in primary care patients.AF patients from a Brazilian primary care population had a higher risk of death for all causes (HR 2.10, 95%CI 2.03-2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86-2.29).Female patients with AF had an increased risk of overall and cardiovascular mortality compared with male patients (p < 0.001).

Evaluation of mortality in bundle branch block patients from an electronic cohort: Clinical Outcomes in Digital Electrocardiography (CODE) study.

BACKGROUND: Left bundle branch block is recognized as a marker of higher risk of death, but the prognostic value of the right bundle branch block in the general population is still controversial. Our aim is to evaluate the risk of overall and cardiovascular mortality in patients with right (RBBB) and left bundle branch block (LBBB) in a large electronic cohort of Brazilian patients. METHODS: This observational retrospective study was developed with the database of digital ECGs from Telehealth Network of Minas Gerais, Brazil (TNMG). All ECGs performed from 2010 to 2017 in primary care patients over 16 years old were assessed. The electronic cohort was obtained by linking data from ECG exams (name, sex, date of birth, city of residence) and those from national mortality information system, using standard probabilistic linkage methods (FRIL: Fine-grained record linkage software, v.2.1.5, Atlanta, GA). Only the first ECG of each patient was considered. Clinical data were self-reported, and ECGs were interpreted manually by cardiologists and automatically by the Glasgow University Interpreter software. Hazard ratio (HR) for mortality was estimated using Cox regression. RESULTS: From a dataset of 1,773,689 patients, 1,558,421 primary care patients over 16 years old underwent a valid ECG recording during 2010 to 2017. We excluded 17,359 patients that didn't have a valid QRS measure from the Glasgow program and 11,091 patients from the control group that had QRS equal or above 120 ms and were not RBBB or LBBB. Therefore, 1,529,971 were included (median age 52 [Q1:38; Q3:65] years; 40.2% were male). In a mean follow-up of 3.7 years, the overall mortality rate was 3.34%. RBBB was more frequent (2.42%) than LBBB (1.32%). In multivariate analysis, adjusting for sex, age and comorbidities, both patients with RBBB (HR 1.32; CI 95% 1.27-1.37) and LBBB (HR 1.69; CI 95% 1.62-1.76) had higher risk of overall mortality. Women with RBBB had an increased risk of all-cause death compared to men (p < 0.001). Cardiovascular mortality was higher in patients with LBBB (HR 1.77; CI 95% 1.55-2.01), but not for RBBB. CONCLUSIONS: Patients with RBBB and LBBB had higher risk of overall mortality. Women with RBBB had more risk of all-cause death than men. LBBB was associated with higher risk of cardiovascular mortality.

Tele-electrocardiography and bigdata: The CODE (Clinical Outcomes in Digital Electrocardiography) study.

Digital electrocardiographs are now widely available and a large number of digital electrocardiograms (ECGs) have been recorded and stored. The present study describes the development and clinical applications of a large database of such digital ECGs, namely the CODE (Clinical Outcomes in Digital Electrocardiology) study. ECGs obtained by the Telehealth Network of Minas Gerais, Brazil, from 2010 to 17, were organized in a structured database. A hierarchical free-text machine learning algorithm recognized specific ECG diagnoses from cardiologist reports. The Glasgow ECG Analysis Program provided Minnesota Codes and automatic diagnostic statements. The presence of a specific ECG abnormality was considered when both automatic and medical diagnosis were concordant; cases of discordance were decided using heuristisc rules and manual review. The ECG database was linked to the national mortality information system using probabilistic linkage methods. From 2,470,424 ECGs, 1,773,689 patients were identified. After excluding the ECGs with technical problems and patients <16 years-old, 1,558,415 patients were studied. High performance measures were obtained using an end-to-end deep neural network trained to detect 6 types of ECG abnormalities, with F1 scores >80% and specificity >99% in an independent test dataset. We also evaluated the risk of mortality associated with the presence of atrial fibrillation (AF), which showed that AF was a strong predictor of cardiovascular mortality and mortality for all causes, with increased risk in women. In conclusion, a large database that comprises all ECGs performed by a large telehealth network can be useful for further developments in the field of digital electrocardiography, clinical cardiology and cardiovascular epidemiology.