Highlights from the Ninth International Symposium of Thrombosis and Anticoagulation (ISTA IX), October 15, 2016, Salvador, Bahia, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Ninth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, on October 15, 2016. This scientific program was developed by clinicians for clinicians and was promoted by two major clinical research institutes-the Brazilian Clinical Research Institute and the Duke Clinical Research Institute of the Duke University School of Medicine. Comprising academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Independent and Added Value of Cardiopulmonary Exercise Testing to New York Heart Association Classification in Patients With Heart Failure.

PURPOSE: The objective of this study was to evaluate the independent and added value of a cardiopulmonary exercise test (CPX) to New York Heart Association (NYHA) functional analysis in patients with heart failure (HF) and ejection fraction (EF) <50%. METHODS: Patients (n = 613) with HF and EF < 50% underwent CPX and were followed for 28 ± 17 mo with respect to primary outcomes (death or heart transplantation). RESULTS: Mean patient age was 56 ± 12 yr, and 64% were male. Most patients were classified as NYHA class II (41%). The composite rate of primary outcomes was 12%; death occurred in 9%, and heart transplant in 4%. Independent predictors of primary outcomes were: EF (HR = 0.95: 95% CI, 0.92-0.98; P = .001) and NYHA (HR = 2.06: 95% CI, 1.54-2.75; P < .0001). When added to the model, peak oxygen uptake (V˙ O2peak ) was an independent predictor (HR = 0.90: 95% CI, 0.84-0.96; P = .001), as was the percentage of predicted V˙ O2peak (HR = 0.03: 95% CI, 0.007-0.147; P < .001), minute ventilation/carbon dioxide production slope (HR = 1.02: 95% CI, 1.01-1.04; P = .012), and CPX score (HR = 1.16: 95% CI, 1.06-1.27; P = .001). CONCLUSIONS: CPX variables were independent predictors of HF prognosis, even when controlled by NYHA functional class. Despite being independent predictors, the value added to NYHA classification was modest and lacked statistical significance.

Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement. / Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. OBJECTIVES: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. METHODS: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ -17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. RESULTS: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was -19% (-16% to -20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). CONCLUSION: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

FUNDAMENTO: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T\TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. OBJETIVOS: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. MÉTODOS: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. RESULTADOS: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% ­ −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29­49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61­0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). CONCLUSÃO: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Highlights from the IV International Symposium of Thrombosis and Anticoagulation (ISTA), October 20-21, 2011, Salvador, Bahia, Brazil.

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fourth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, from October 20-21, 2011. This scientific program was developed by clinicians for clinicians and was promoted by three major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, and Hospital do Coração Research Institute. Comprising 2 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Low Concordance between NYHA Classification and Cardiopulmonary Exercise Test Variables in Patients with Heart Failure and Reduced Ejection Fraction. / Baixa Concordância entre a Classificação da NYHA e as Variáveis do Teste de Exercício Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida.

BACKGROUND: The New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF. OBJECTIVE: This study aimed to analyze correlation and concordance between NYHA classes and CPET variables. METHODS: HF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant. RESULTS: In total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO2] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606). CONCLUSION: There was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO2slope) and CPET score classes had a weak association and a low concordance with NYHA classes.

FUNDAMENTO: A classificação funcional da New York Heart Association (NYHA) é o sistema de classificação mais utilizado para a insuficiência cardíaca (IC), enquanto o teste de exercício cardiopulmonar (TECP) é o padrão ouro para a avaliação do estado funcional na IC. OBJETIVO: Analisar a correlação e a concordância entre as classes da NYHA e as variáveis do TECP. MÉTODOS: Foram selecionados pacientes com IC com indicação clínica para TECP e fração de ejeção (FE) < 50%. A correlação (coeficiente de Spearman) e a concordância (kappa) entre a classificação da NYHA e as classificações baseadas no TECP foram analisadas. Um valor de p < 0,05 foi considerado significativo. RESULTADOS: No total, foram incluídos 244 pacientes no estudo. A idade média foi de 56±14 anos, e a FE média foi de 35,5%±10%. A distribuição de pacientes de acordo com a classificação da NYHA foi a seguinte: classe I (31,2%), classe II (48,3%), classe III (19,2%) e classe IV (1,3%). A correlação (r) entre as classes da NYHA e de Weber foi de 0,489 (p < 0,001), e a concordância foi de 0,231 (p < 0,001). A correlação (r) entre as classes da NYHA e ventilatórias (inclinação da ventilação minuto/produção de dióxido de carbono [VE/VCO2]) foi de 0,218 (p < 0,001), e a concordância foi de 0,002 (p = 0,959). A correlação de Spearman entre as classes da NYHA e do escore TECP foi de 0,223 (p = 0,004), e a concordância kappa foi de 0,027 (p = 0,606). CONCLUSÃO: Foi identificada uma associação moderada entre as classes da NYHA e de Webber, embora a concordância tenha sido baixa. As classes ventilatórias (inclinação VE/VCO2) e do escore TECP apresentaram uma associação fraca e uma baixa concordância com as classes da NYHA.

The Six-Minute Step Test as a Predictor of Functional Capacity according to Peak VO2 in Cardiac Patients. / O Teste do Degrau de Seis Minutos como Preditor de Capacidade Funcional de Acordo com o Consumo de Oxigênio de Pico em Pacientes Cardíacos.

BACKGROUND: Six-minute step test (6MST) is a simple way to evaluate functional capacity, although it has not been well studied in patients with coronary artery disease (CAD) or heart failure (HF). OBJECTIVE: Analyze the association between the 6MST and peak oxygen uptake (VO2peak) and develop an equation for estimating VO2peak based on the 6MST, as well as to determine a cutoff point for the 6MST that predicts a VO2peak ≥20 mL.Kg-1.min-1. METHODS: In 171 patients who underwent the 6MST and a cardiopulmonary exercise test, correlation, regression, and ROC analysis were used and a p < 0.05 was admitted as significant. RESULTS: mean age was 60±14 years and 74% were male. Mean left ventricle ejection fraction was 57±16%, 74% had CAD and 28% had HF. Mean VO2peak was 19±6 mL.Kg-1.min-1 and mean 6MST performance was 87±45 steps. Association between 6MST and VO2peak was r 0.69 (p <0.001). The model VO2peak =19.6 + (0.075 x 6MST) - (0.10 x age) for men and VO2peak =19.6 + (0.075 x 6MST) - (0.10 x age) - 2 for women could predict VO2peak based on 6MST results (adjusted R 0.72; adjusted R2 0.53). The most accurate cutoff point for 6MST to predict a VO2peak ≥20 mL.Kg-1.min-1 was >105 steps (AUC 0.85; 95% CI 0.79 -0.90; p <0.001). CONCLUSION: An equation for predicting VO2peak based on 6MST results was derived, and a significant association was found between 6MST and VO2peak. The cutoff point for 6MST, which predicts a VO2peak ≥20 mL.Kg-1.min-1, was >105 steps. (Arq Bras Cardiol. 2021; 116(5):889-895).

FUNDAMENTO: O teste do degrau de seis minutos (TD6) é uma forma simples de avaliar a capacidade funcional, embora tenha sido pouco estudado em pacientes com doença arterial coronariana (DAC) ou insuficiência cardíaca (IC). OBJETIVO: Analisar a associação entre o TD6 e o consumo de oxigênio de pico (VO2pico) e desenvolver uma equação que estime o VO2pico com base no TD6, bem como determinar um ponto de corte para o TD6 que preveja um VO2pico ≥ 20 mL.kg-1.min-1. MÉTODOS: Nos 171 pacientes submetidos ao TD6 e a um teste de exercício cardiopulmonar, análises da curva ROC, de regressão e de correlação foram usadas, e um p < 0,05 foi admitido como significativo. RESULTADOS: A idade média foi 60±14 anos, e 74% eram do sexo masculino. A média da fração de ejeção ventricular esquerda foi 57±16%; 74% apresentavam DAC, e 28%, IC. A média do VO2pico foi 19±6 mL.kg-1.min-1, e o desempenho médio do TD6 foi 87±45 passos. A associação entre o TD6 e o VO2pico foi r 0,69 (p < 0,001). Os modelos VO2pico = 19,6 + (0,075 x TD6) ­ (0,10 x idade) para homens e VO2pico = 19,6 + (0,075 x TD6) ­ (0,10 x idade) ­ 2 para mulheres poderiam prever o VO2pico com base nos resultados do TD6 (R ajustado 0,72; R2 ajustado 0,53). O ponto de corte mais acurado para que o TD6 preveja um VO2pico ≥ 20 mL.kg-1.min-1 foi de > 105 passos [área sob a curva 0,85; intervalo de confiança de 95% 0,79 - 0,90; p < 0,001]. CONCLUSÃO: Uma equação que preveja o VO2pico com base nos resultados do TD6 foi derivada, e foi encontrada uma associação significativa entre o TD6 e o VO2pico. O ponto de corte do TD6, que prevê um VO2pico ≥ 20 mL.kg-1.min-1, foi > 105 passos. (Arq Bras Cardiol. 2021; 116(5):889-895).

[Impact of a program for venous thromboembolism prophylaxis in hospitalized patients in four hospitals in Salvador]. / Impacto de um programa para profilaxia de tromboembolismo venoso em pacientes clínicos em quatro hospitais de Salvador.

UNLABELLED: There is a discrepancy between guideline recommendations and practice of venous thromboembolism (VTE) prophylaxis in hospitals worldwide. OBJECTIVE: To implement a program using a risk-assessment tool (RAT) for VTE and educational lectures based on the Brazilian Guidelines for VTE Prophylaxis for Medical Patients and to evaluate the impact of these tools on adequacy of VTE prophylaxis in 4 hospitals in Salvador, Bahia. METHODS: We performed two cross-sectional surveys before and after the implementation of the program to compare the proportion of patients at-risk of VTE and the changes in the adequacy of VTE prophylaxis. RESULTS: We compared the data of 219 medical patients before with 292 patients after the program. The rates of patients with at least one risk factor for VTE and with contraindications (CI) for heparins were similar: 95% vs. 98% (p=0.13), and 42% vs. 34% (p=0.08), respectively. In both studies, 75% vs. 82% (p=0.06) were candidates for prophylaxis, and 44% vs. 55% (p =0.02) were candidates for prophylaxis and had no CI for heparin. After the program there was an increase in the use of mechanical prophylaxis 0.9% vs. 4.5% (p=0.03) and a decrease in pharmacological prophylaxis, 55.3% vs. 47.9% (p=0.04). However, there was a significant increase of use of the recommended doses of heparins, 53% vs. 75 (p<0.001). CONCLUSION: There is underutilization of VTE prophylaxis in Brazilian hospitals. Strategies based on passive distribution of RAT and educational lectures were not sufficient to improve the practice of prophylaxis, but improved the adequacy of VTE prophylaxis in hospitalized patients.

Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review.

BACKGROUND: Takotsubo syndrome (TTS) is characterized by a temporary systolic dysfunction of the left ventricle (LV) related to a stressful event. However, the factors associated with its recurrence are still not well established. OBJECTIVE: To analyze the main factors associated with TTS recurrence. METHODS: A systematic review was performed using the PRISMA model. Observational studies, published between January 2008 and October 2017, which presented a recurrence rate of at least 3% and/or 5 or more patients with recurrence, and who met at least 80% of the STROBE criteria were included. RESULTS: six articles reached the criteria to compose this systematic review. The recurrence rate ranged from 1 to 3.5% per year (global recurrence rate 3.8%). One study associated higher recurrence rate with the female gender, four reported the time between the first and second episodes, one study associated body mass index (BMI) and hypercontractility of the LV middle anterior wall to a higher recurrence rate. No association between recurrence and electrocardiographic changes were determined. Beta-blockers use was not associated with recurrence rates. CONCLUSIONS: Female gender, time from the first episode of the syndrome, low BMI and midventricular obstruction were reported as potential predictors of TTS recurrence.

Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto / Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement

Resumo Fundamento: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T/TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. Objetivos: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. Métodos: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. Resultados: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% - −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29-49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61-0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). Conclusão: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Abstract Background: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. Objectives: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. Methods: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ −17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. Results: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was −19% (−16% to −20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). Conclusion: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

Acute pulmonary embolism is an independent predictor of adverse events in severe decompensated heart failure patients.

BACKGROUND: Congestive heart failure (CHF) is a well-recognized risk factor for venous thromboembolism (VTE) and is associated with higher mortality in patients with an acute pulmonary embolism (PE). There are very few data on how acute PE affects the clinical course of patients with heart failure. The purpose of this study was to determine the impact of an acute PE on the short-term prognosis of patients hospitalized for decompensated CHF. METHODS: This was a prospective cohort study of 198 patients admitted to a coronary care unit between July 2001 and March 2003 with severe decompensated CHF. The primary outcome measure was death or rehospitalization at 3 months. RESULTS: PE was confirmed in 18 of 198 patients enrolled (9.1%). The groups with and without PE were comparable with regards to demographics, the prevalence of comorbid conditions, and severity of CHF (p > 0.05). The prevalence of cancer (p = 0.0001), previous VTE (p = 0.003), and right ventricular overload (p = 0.006) was higher in the PE group. The presence of PE was also associated with a longer hospital stay (37.5 +/- 71.6 days vs 15.4 +/- 15.0 days, p = 0.001) [mean +/- SD] and a higher incidence of death or rehospitalization at 3 months (72.2% vs 43.9%, p = 0.02). In a multiple logistic regression analysis, PE remained an independent predictor of death or rehospitalization at 3 months (odds ratio, 4.0; 95% confidence interval, 1.1 to 15.1; p = 0.038). CONCLUSIONS: Acute PE commonly complicates the hospital course of patients with severe CHF, increasing the length of hospital stay and the chance of death or rehospitalization at 3 months.

Cardiovascular function in normotensive offspring of persons with essential hypertension and black race.

Prior investigations have shown impaired endothelial function in hypertensive blacks when compared with whites. It is not clear, however, whether the difference in vascular responsiveness predates or follows the development of hypertension. Thirty-nine young black adults with a family history of essential hypertension and 41 control participants were studied for brachial artery reactivity and carotid intima-media thickness via ultrasonography, cardiac muscle mass and diastolic function by echocardiography, and biochemical analysis. There was no significant difference in brachial artery reactivity between the study groups, although women had greater reactivity than men (P=.05). Carotid intima-media thickness, left ventricular geometry, and biomarkers were equivalent between the study groups (P=not significant). Vascular imaging and biomarkers were unable to identify early evidence of endothelial dysfunction in offspring of African Americans with essential hypertension. These same studies demonstrated some early changes in vascular function based on sex.

Baixa Concordância entre a Classificação da NYHA e as Variáveis do Teste de Exercício Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida / Low Concordance between NYHA Classification and Cardiopulmonary Exercise Test Variables in Patients with Heart Failure and Reduced Ejection Fraction

Resumo Fundamento A classificação funcional da New York Heart Association (NYHA) é o sistema de classificação mais utilizado para a insuficiência cardíaca (IC), enquanto o teste de exercício cardiopulmonar (TECP) é o padrão ouro para a avaliação do estado funcional na IC. Objetivo Analisar a correlação e a concordância entre as classes da NYHA e as variáveis do TECP. Métodos Foram selecionados pacientes com IC com indicação clínica para TECP e fração de ejeção (FE) < 50%. A correlação (coeficiente de Spearman) e a concordância (kappa) entre a classificação da NYHA e as classificações baseadas no TECP foram analisadas. Um valor de p < 0,05 foi considerado significativo. Resultados No total, foram incluídos 244 pacientes no estudo. A idade média foi de 56±14 anos, e a FE média foi de 35,5%±10%. A distribuição de pacientes de acordo com a classificação da NYHA foi a seguinte: classe I (31,2%), classe II (48,3%), classe III (19,2%) e classe IV (1,3%). A correlação (r) entre as classes da NYHA e de Weber foi de 0,489 (p < 0,001), e a concordância foi de 0,231 (p < 0,001). A correlação (r) entre as classes da NYHA e ventilatórias (inclinação da ventilação minuto/produção de dióxido de carbono [VE/VCO2]) foi de 0,218 (p < 0,001), e a concordância foi de 0,002 (p = 0,959). A correlação de Spearman entre as classes da NYHA e do escore TECP foi de 0,223 (p = 0,004), e a concordância kappa foi de 0,027 (p = 0,606). Conclusão Foi identificada uma associação moderada entre as classes da NYHA e de Webber, embora a concordância tenha sido baixa. As classes ventilatórias (inclinação VE/VCO2) e do escore TECP apresentaram uma associação fraca e uma baixa concordância com as classes da NYHA.

Abstract Background The New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF. Objective This study aimed to analyze correlation and concordance between NYHA classes and CPET variables. Methods HF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant. Results In total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO2] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606). Conclusion There was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO2slope) and CPET score classes had a weak association and a low concordance with NYHA classes.

Comparison of the effect of anemia on in-hospital mortality in patients with versus without preserved left ventricular ejection fraction.

Patients with symptomatic heart failure (HF) frequently have preserved left ventricular (LV) ejection fractions (LVEFs). Although anemia is a common finding in this patient population, its prognostic role has not been well studied. This study's aim was to assess if the LVEF interferes in the association between anemia and in-hospital mortality in patients with severe HF. Consecutive patients admitted to an intensive care unit with decompensated chronic HF were prospectively enrolled. The diagnosis of HF was based on clinical criteria. Patients with LVEFs > or =45% (on echocardiography) were diagnosed as having preserved LVEFs. Multivariate analysis was performed to test the independent association between anemia and in-hospital mortality and to evaluate an interaction between anemia and systolic function. In all, 303 patients were recruited (mean age 69 +/- 13 years; 45.5% women). Preserved LVEFs were present in 34% of the population. The prevalence of anemia in this group was 58%, compared with 43% in the group with systolic dysfunction (p = 0.01). Dilated left ventricles, left bundle branch blocks, and valvular dysfunction were significantly more frequent in patients with systolic heart failure. In-hospital mortality was similar in the groups with preserved LVEFs and systolic dysfunction (p = 0.71). On multivariate analysis, anemia was independently associated with in-hospital mortality (odds ratio 2.7, 95% confidence interval 1.43 to 5.04, p = 0.002). There was no interaction between anemia and systolic function (p = 0.08 for interaction). In conclusion, anemia was an independent predictor of in-hospital mortality in symptomatic patients with severe HF, regardless of whether the patients had preserved or impaired LV systolic function.

Pulmonary Embolism Mortality in Brazil from 1989 to 2010: Gender and Regional Disparities.

BACKGROUND: A significant variation in pulmonary embolism (PE) mortality trends have been documented around the world. We investigated the trends in mortality rate from PE in Brazil over a period of 21 years and its regional and gender differences. METHODS: Using a nationwide database of death certificate information we searched for all cases with PE as the underlying cause of death between 1989 and 2010. Population data were obtained from the Brazilian Institute of Geography and Statistics (IBGE). We calculated age-, gender- and region-specific mortality rates for each year, using the 2000 Brazilian population for direct standardization. RESULTS: Over 21 years the age-standardized mortality rate (ASMR) fell 31% from 3.04/100,000 to 2.09/100,000. In every year between 1989 and 2010, the ASMR was higher in women than in men, but both showed a significant declining trend, from 3.10/100,000 to 2.36/100,000 and from 2.94/100,000 to 1.80/100,000, respectively. Although all country regions showed a decline in their ASMR, the largest fall in death rates was concentrated in the highest income regions of the South and Southeast Brazil. The North and Northeast regions, the lowest income areas, showed a less marked fall in death rates and no distinct change in the PE mortality rate in women. CONCLUSIONS: Our study showed a reduction in the PE mortality rate over two decades in Brazil. However, significant variation in this trend was observed amongst the five country regions and between genders, pointing to possible disparities in health care access and quality in these groups.

O Teste do Degrau de Seis Minutos como Preditor de Capacidade Funcional de Acordo com o Consumo de Oxigênio de Pico em Pacientes Cardíacos / The Six-Minute Step Test as a Predictor of Functional Capacity according to Peak VO2 in Cardiac Patients

Resumo Fundamento: O teste do degrau de seis minutos (TD6) é uma forma simples de avaliar a capacidade funcional, embora tenha sido pouco estudado em pacientes com doença arterial coronariana (DAC) ou insuficiência cardíaca (IC). Objetivo: Analisar a associação entre o TD6 e o consumo de oxigênio de pico (VO2pico) e desenvolver uma equação que estime o VO2pico com base no TD6, bem como determinar um ponto de corte para o TD6 que preveja um VO2pico ≥ 20 mL.kg-1.min-1 Métodos: Nos 171 pacientes submetidos ao TD6 e a um teste de exercício cardiopulmonar, análises da curva ROC, de regressão e de correlação foram usadas, e um p < 0,05 foi admitido como significativo. Resultados: A idade média foi 60±14 anos, e 74% eram do sexo masculino. A média da fração de ejeção ventricular esquerda foi 57±16%; 74% apresentavam DAC, e 28%, IC. A média do VO2pico foi 19±6 mL.kg-1.min-1, e o desempenho médio do TD6 foi 87±45 passos. A associação entre o TD6 e o VO2pico foi r 0,69 (p < 0,001). Os modelos VO2pico = 19,6 + (0,075 x TD6) - (0,10 x idade) para homens e VO2pico = 19,6 + (0,075 x TD6) - (0,10 x idade) - 2 para mulheres poderiam prever o VO2pico com base nos resultados do TD6 (R ajustado 0,72; R2 ajustado 0,53). O ponto de corte mais acurado para que o TD6 preveja um VO2pico ≥ 20 mL.kg-1.min-1 foi de > 105 passos [área sob a curva 0,85; intervalo de confiança de 95% 0,79 - 0,90; p < 0,001]. Conclusão: Uma equação que preveja o VO2pico com base nos resultados do TD6 foi derivada, e foi encontrada uma associação significativa entre o TD6 e o VO2pico. O ponto de corte do TD6, que prevê um VO2pico ≥ 20 mL.kg-1.min-1, foi > 105 passos. (Arq Bras Cardiol. 2021; 116(5):889-895)

Abstract Background: Six-minute step test (6MST) is a simple way to evaluate functional capacity, although it has not been well studied in patients with coronary artery disease (CAD) or heart failure (HF). Objective: Analyze the association between the 6MST and peak oxygen uptake (VO2peak) and develop an equation for estimating VO2peak based on the 6MST, as well as to determine a cutoff point for the 6MST that predicts a VO2peak ≥20 mL.Kg-1.min-1 Methods: In 171 patients who underwent the 6MST and a cardiopulmonary exercise test, correlation, regression, and ROC analysis were used and a p < 0.05 was admitted as significant. Results: mean age was 60±14 years and 74% were male. Mean left ventricle ejection fraction was 57±16%, 74% had CAD and 28% had HF. Mean VO2peak was 19±6 mL.Kg-1.min-1 and mean 6MST performance was 87±45 steps. Association between 6MST and VO2peak was r 0.69 (p <0.001). The model VO2peak =19.6 + (0.075 x 6MST) - (0.10 x age) for men and VO2peak =19.6 + (0.075 x 6MST) - (0.10 x age) - 2 for women could predict VO2peak based on 6MST results (adjusted R 0.72; adjusted R2 0.53). The most accurate cutoff point for 6MST to predict a VO2peak ≥20 mL.Kg-1.min-1 was >105 steps (AUC 0.85; 95% CI 0.79 -0.90; p <0.001). Conclusion: An equation for predicting VO2peak based on 6MST results was derived, and a significant association was found between 6MST and VO2peak. The cutoff point for 6MST, which predicts a VO2peak ≥20 mL.Kg-1.min-1, was >105 steps. (Arq Bras Cardiol. 2021; 116(5):889-895)

Incidence and clinical predictors of pulmonary embolism in severe heart failure patients admitted to a coronary care unit.

OBJECTIVES: To determine the incidence of clinical pulmonary embolism (PE) in a population with severe congestive heart failure (CHF) admitted to a coronary care unit (CCU), and to identify clinical predictors of PE in this population. DESIGN AND SETTING: Prospective, observational study performed in a CCU of a tertiary care hospital between July 2001 and March 2003. PATIENTS: One hundred ninety-eight patients with severe decompensated CHF. MEASUREMENTS AND RESULTS: Of 198 patients recruited, 18 patients (9.1%) received a diagnosis of PE during their hospitalization. Deep vein thrombosis was demonstrated in 8 of 18 patients (44.4%) with PE. Thromboprophylaxis was used by 12 of 18 patients (66.7%) with PE and 126 of 180 patients (70%) without PE (p = 0.77). Both groups were similar with respect to mean age (68.2 +/- 14.1 years vs 69.6 +/- 13.4 years [+/- SD]), proportion of male patients (61.1% vs 55.1%), markers of CHF severity (New York Heart Association functional class > II, ejection fraction < 30%, Na < 136 mEq/L, ischemic etiology), and comorbid conditions (diabetes mellitus, atrial fibrillation, chronic renal failure, hypertension) [p = not significant]. The presence of PE was significantly associated with cancer (relative risk [RR], 8.4; 95% confidence interval [CI], 3.9 to 18.1), immobilization (RR, 5.4; 95% CI, 2.0 to 14.4), previous venous thromboembolism (VTE) [RR, 4.4; 95% CI, 1.7 to 11.3], COPD (RR, 3.1; 95% CI, 1.03 to 9.2), and right ventricle (RV) abnormality (RR, 3.3; 95% CI, 1.3 to 8.0). In a multiple logistic regression analysis, only cancer (odds ratio [OR], 26.9; 95% CI, 4.9 to 146.8), RV abnormality (OR, 9.7; 95% CI, 2.2 to 42.6), and previous VTE (OR, 9.1; 95% CI, 1.28 to 64.7) remained independently associated with PE. CONCLUSIONS: In patients with severe decompensated CHF admitted to a CCU, the incidence of clinical PE is very high despite adequate prophylaxis. Traditional risk factors seemed to play an important role in determining the risk of PE in this population.

Trends and Predictors of Oral Anticoagulation in Patients with Atrial Fibrillation: A Serial Cross-Sectional Study from 2011 to 2016

Abstract Background: Despite the efficacy of vitamin K antagonists against stroke in patients with atrial fibrillation (AF), the underuse of this therapy is well documented. Objectives: To evaluate trends and predictors of oral anticoagulants utilization in patients with AF. Methods: Observational, retrospective, serial cross-sectional study between 2011-2016. Comparisons between groups were performed using the Student t, Mann-Whitney and Chi-square tests. Logistic regression was used to identify independent predictors of anticoagulation. A p value < 0.05 was considered significant. Results: A total of 377 patients were analyzed. The mean age was 70 ± 15 years; 52% were male and 75% were anticoagulated (20% with VKA and 55% with DOAC). Over 5 years, the overall frequency of anticoagulation increased by 22.4%. The use of DOACs increased from 29% to 70%, whereas the use of VKA decreased from 36% to 17%. The use of antiplatelet agents alone also fell from 21% to 6%. The predictors of anticoagulation were previous episodes of AF (OR 3.1, p < 0.001), hypertension (OR 3.0, p < 0.001) and HASBLED score (OR 0.5, p < 0.001). The predictors of DOAC use were serum creatinine (OR 0.2, p = 0.002), left atrial size (OR 0.9, p = 0.003) and biological valve prosthesis (OR 0.1, p = 0.007). Of the 208 patients using DOACs, 63 (30%) received inadequate prescriptions: 5 with severe drug interactions and 58 with incorrect dosing. Conclusions: Between 2011 and 2016, DOACs were rapidly incorporated into clinical practice, replacing AVKs and antiplatelets, and contributing to greater use of anticoagulation in patients with AF.

Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review / Fatores Associados à Recorrência na Síndrome de Takotsubo: Uma Revisão Sistemática

Abstract Background: Takotsubo syndrome (TTS) is characterized by a temporary systolic dysfunction of the left ventricle (LV) related to a stressful event. However, the factors associated with its recurrence are still not well established. Objective: To analyze the main factors associated with TTS recurrence. Methods: A systematic review was performed using the PRISMA model. Observational studies, published between January 2008 and October 2017, which presented a recurrence rate of at least 3% and/or 5 or more patients with recurrence, and who met at least 80% of the STROBE criteria were included. Results: six articles reached the criteria to compose this systematic review. The recurrence rate ranged from 1 to 3.5% per year (global recurrence rate 3.8%). One study associated higher recurrence rate with the female gender, four reported the time between the first and second episodes, one study associated body mass index (BMI) and hypercontractility of the LV middle anterior wall to a higher recurrence rate. No association between recurrence and electrocardiographic changes were determined. Beta-blockers use was not associated with recurrence rates. Conclusions: Female gender, time from the first episode of the syndrome, low BMI and midventricular obstruction were reported as potential predictors of TTS recurrence.

Resumo Fundamento: A síndrome de Takotsubo (STT) é caracterizada por uma disfunção sistólica temporária do ventrículo esquerdo (VE) relacionada a um evento estressante. No entanto, os fatores associados à sua recorrência ainda não estão bem estabelecidos. Objetivo: Analisar os principais fatores associados à recorrência da STT. Métodos: Uma revisão sistemática foi realizada usando o modelo PRISMA. Foram incluídos estudos observacionais, publicados entre janeiro de 2008 e outubro de 2017, que apresentaram uma taxa de recorrência de pelo menos 3% e/ou 5 ou mais pacientes com recidiva e que preencheram pelo menos 80% dos critérios STROBE. Resultados: Seis artigos atenderam aos critérios para esta revisão sistemática. A taxa de recorrência variou de 1 a 3,5% ao ano (taxa de recorrência global 3,8%). Um estudo associou maior taxa de recorrência ao sexo feminino, quatro relataram o tempo entre o primeiro e o segundo episódio, um estudo associou o índice de massa corporal (IMC) e a hipercontratilidade da parede anterior média do VE a uma maior taxa de recorrência. Não foi determinada associação entre recorrência e alterações eletrocardiográficas. O uso de betabloqueadores não foi associado a taxas de recorrência. Conclusões: Sexo feminino, tempo desde o primeiro episódio da síndrome, baixo IMC e obstrução ventricular foram relatados como possíveis preditores de recorrência da STT.