Echocardiographic Predictors of Worse Outcome After Cardiac Resynchronization Therapy / Parâmetros Ecocardiográficos Preditores de Pior Evolução após a Terapia de Ressincronização Cardíaca

Abstract Background: Cardiac resynchronization therapy (CRT) is the recommended treatment by leading global guidelines. However, 30%-40% of selected patients are non-responders. Objective: To develop an echocardiographic model to predict cardiac death or transplantation (Tx) 1 year after CRT. Method: Observational, prospective study, with the inclusion of 116 patients, aged 64.89 ± 11.18 years, 69.8% male, 68,1% in NYHA FC III and 31,9% in FC IV, 71.55% with left bundle-branch block, and median ejection fraction (EF) of 29%. Evaluations were made in the pre‑implantation period and 6-12 months after that, and correlated with cardiac mortality/Tx at the end of follow-up. Cox and logistic regression analyses were performed with ROC and Kaplan-Meier curves. The model was internally validated by bootstrapping. Results: There were 29 (25%) deaths/Tx during follow-up of 34.09 ± 17.9 months. Cardiac mortality/Tx was 16.3%. In the multivariate Cox model, EF < 30%, grade III/IV diastolic dysfunction and grade III mitral regurgitation at 6‑12 months were independently related to increased cardiac mortality or Tx, with hazard ratios of 3.1, 4.63 and 7.11, respectively. The area under the ROC curve was 0.78. Conclusion: EF lower than 30%, severe diastolic dysfunction and severe mitral regurgitation indicate poor prognosis 1 year after CRT. The combination of two of those variables indicate the need for other treatment options.

Resumo Fundamento: A terapia de ressincronização cardíaca (TRC) é um tratamento recomendado pelas principais diretrizes mundiais. Entretanto, 30%-40% dos pacientes selecionados não respondem ao tratamento. Objetivo: Elaborar um modelo ecocardiográfico preditor de risco de óbito cardíaco ou transplante (Tx) após 1 ano da TRC. Método: Estudo observacional, prospectivo, com inclusão de 116 pacientes, sendo 69,8% do sexo masculino, com idade de 64,89 ± 11,18 anos, CF III (68,1%) e IV ambulatorial (31,9%), bloqueio de ramo esquerdo em 71,55%, e mediana da fração de ejeção (FE) de 29%. Avaliações foram feitas no período pré-implante e 6-12 meses após, e correlacionadas com mortalidade cardíaca/Tx no final do seguimento. Foram realizadas análises de regressão de Cox e logística, com a curva ROC e de sobrevida de Kaplan-Meier. O modelo foi validado internamente pelo “bootstrapping”. Resultados: Ocorreram 29 (25%) óbitos/Tx durante o seguimento de 34,09 ± 17,9 meses. A mortalidade cardíaca/Tx foi de 16,3 %. No modelo multivariado de Cox, as variáveis FE < 30%, disfunção diastólica grau III/IV e regurgitação mitral grau III, aferidas com 6-12 meses, relacionaram-se independentemente a aumento de mortalidade cardíaca ou Tx, com razões de risco de 3,1, 4,63 e 7,11, respectivamente. A área sob a curva ROC foi de 0,78. Conclusão: FE menor que 30%, disfunção diastólica grave e regurgitação mitral severa indicam pior prognóstico após 1 ano da TRC, devendo ser consideradas outras opções terapêuticas na presença da combinação de duas dessas variáveis.

Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy.

BACKGROUND: 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes. OBJECTIVE: This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT). METHODS: Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves. RESULTS: The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping. CONCLUSION: We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy / Desenvolvimento e Validação de Modelos Preditores de Mortalidade Cardíaca e Transplante na Terapia de Ressincronização Cardíaca

AbstractBackground:30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes.Objective:This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT).Methods:Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves.Results:The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping.Conclusion:We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

ResumoFundamento:A terapia de ressincronização cardíaca pode demonstrar resultados desfavoráveis em 30-40% dos casos.Objetivo:Este estudo teve por objetivo desenvolver modelos preditores para o desfecho combinado de morte cardíaca ou transplante (Tx) em diferentes estágios da terapia de ressincronização cardíaca (TRC).Métodos:Estudo prospectivo observacional de 116 pacientes com idade média de 64,8 ± 11,1 anos, dos quais 68,1% estavam em classe funcional (CF) III e 31,9% em classe IV ambulatorial. Variáveis clínicas, eletrocardiográficas e ecocardiográficas foram avaliadas com regressão de Cox e curvas de Kaplan-Meier.Resultados:O desfecho mortalidade/Tx cardíacos foi de 16,3% durante seguimento de 34,0 ± 17,9 meses. No período pré-implante, disfunção ventricular direita (DVD), fração de ejeção < 25% e uso de altas doses de diuréticos (ADD) aumentaram o risco de morte e Tx cardíacos em 3,9, 4,8 e 5,9 vezes, respectivamente. No primeiro ano após TRC, DVD, AHDD e hospitalização por insuficiência cardíaca congestiva elevaram o risco de morte (razões de risco de 3,5, 5,3 e 12,5, respectivamente). No segundo ano após TRC, DVD e CF III/IV foram fatores de risco significativos de mortalidade no modelo multivariado de Cox. As acurácias dos modelos foram 84,6% na pré-implante, 93% no primeiro ano após TRC e 90,5% no segundo ano após TRC. Os modelos foram validados por bootstrapping.Conclusão:Desenvolvemos modelos preditores de morte e Tx cardíacos em diferentes estágios de TRC com base na análise de variáveis clínicas e ecocardiográficas simples e de fácil obtenção. Os modelos mostraram boa acurácia e ajuste, foram validados internamente e são úteis para a seleção, o monitoramento e a orientação de pacientes indicados para TRC.

Echocardiographic Predictors of Worse Outcome After Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is the recommended treatment by leading global guidelines. However, 30%-40% of selected patients are non-responders. OBJECTIVE: To develop an echocardiographic model to predict cardiac death or transplantation (Tx) 1 year after CRT. METHOD: Observational, prospective study, with the inclusion of 116 patients, aged 64.89 ± 11.18 years, 69.8% male, 68,1% in NYHA FC III and 31,9% in FC IV, 71.55% with left bundle-branch block, and median ejection fraction (EF) of 29%. Evaluations were made in the pre­implantation period and 6-12 months after that, and correlated with cardiac mortality/Tx at the end of follow-up. Cox and logistic regression analyses were performed with ROC and Kaplan-Meier curves. The model was internally validated by bootstrapping. RESULTS: There were 29 (25%) deaths/Tx during follow-up of 34.09 ± 17.9 months. Cardiac mortality/Tx was 16.3%. In the multivariate Cox model, EF < 30%, grade III/IV diastolic dysfunction and grade III mitral regurgitation at 6­12 months were independently related to increased cardiac mortality or Tx, with hazard ratios of 3.1, 4.63 and 7.11, respectively. The area under the ROC curve was 0.78. CONCLUSION: EF lower than 30%, severe diastolic dysfunction and severe mitral regurgitation indicate poor prognosis 1 year after CRT. The combination of two of those variables indicate the need for other treatment options.

Cardiovascular disease in patients with end-stage renal disease on hemodialysis in a developing country.

Cardiovascular disease is the main cause of death among patients with end-stage renal disease (ESRD). The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on hemodialysis (HD) in Brazil. Their mean age was 47 ± 39 years. The main risk factors for cardiovascular diseases were arterial hypertension (89.4%), dyslipidemia (78.3%), low high-density lipoprotein levels (84.2%) and low physical activity (64.1%). Family history of coronary insufficiency and high low-density lipoprotein levels were significantly associated with coronary artery disease (P = 0.005 and P = 0.029, respectively). Sedentary life style, diabetes mellitus, secondary hyperparathyroidism and hyperglycemia also showed a significant association with the underlying vascular disease (P = 0.017, P = 0.039, P = 0.037 and P = 0.030, respectively). Hypercalcemia, hypertension and black race were factors significantly associated with left ventricular systolic dysfunction (P = 0.01, P = 0.0013 and P = 0.024, respectively). Our study shows that the most prevalent cardiovascular diseases in patients with ESRD were left ventricular hypertrophy, atherosclerotic disease, valvular disease and coronary artery disease. Hypertension and dyslipidemia were the common risk factors associated with cardiovascular diseases. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on HD in a single center in Brazil.

Allergies and diabetes as risk factors for dengue hemorrhagic fever: results of a case control study.

BACKGROUND: The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with selected co-morbidities are at higher risk of developing DHF. METHODS: A matched case-control study was conducted in a dengue sero-positive population in two Brazilian cities. For each case of DHF, 7 sero-positive controls were selected. Cases and controls were interviewed and information collected on demographic and socio-economic status, reported co-morbidities (diabetes, hypertension, allergy) and use of medication. Conditional logistic regression was used to calculate the strength of the association between the co-morbidities and occurrence of DHF. RESULTS: 170 cases of DHF and 1,175 controls were included. Significant associations were found between DHF and white ethnicity (OR = 4.70; 2.17-10.20), high income (OR = 6.84; 4.09-11.43), high education (OR = 4.67; 2.35-9.27), reported diabetes (OR = 2.75; 1.12-6.73) and reported allergy treated with steroids (OR = 2.94; 1.01-8.54). Black individuals who reported being treated for hypertension had 13 times higher risk of DHF then black individuals reporting no hypertension. CONCLUSIONS: This is the first study to find an association between DHF and diabetes, allergy and hypertension. Given the high case fatality rate of DHF (1-5%), we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in hospital.

Reduced oviposition of Aedes aegypti gravid females in domestic containers with predatory fish.

The presence of pathogens or predators in water may alter oviposition behaviour of gravid female Aedes aegypti mosquitoes. We evaluated the oviposition behaviour of A. aegypti in recipients containing larvivorous fish (Betta splendens and Poecilia reticulata). In four breeders, fish specimens were placed in 15 l of dechlorined water. Four control breeders only contained dechlorined water. Breeders with eucatex ovitraps and approximately 100 male and female mosquitoes were placed in wire netting cages. During a period of 7 weeks, eggs on the ovitraps were counted weekly. The median number of eggs laid in recipients with B. splendens (32.5/week) was lower than in those with P. reticulata (200.5/week) and the control group (186.5/week; P < 0.0001). The oviposition activity index (OAI) for P. reticulata did not show any considerable difference between posture in deposits with and without fish (-0005). Deposits with B. splendens showed a lower position than those used as controls (-0627). We conclude that B. splendens can be used to effectively prevent gravid A. aegypti females from laying eggs in large water containers.

Comparative study of cystatin C and serum creatinine in the estimative of glomerular filtration rate in children.

BACKGROUND: To compare estimated glomerular filtration rate (GFR) by Schwartz formula and cystatin C-derived formula in a large population of children with a large spectrum of renal disease. METHODS: Serum creatinine, cystatin C and estimated GFR were determined in 273 children, 254 with renal disease, and a mean age of 10.0+/-4.4 y. Nineteen children were used as control, with a mean age of 8.5+/-4.2 y. RESULTS: The children had nephrotic syndrome (16.5%), glomerulonephritis (11.4%), neurogenic bladder (11.4%), hydronephrosis (9.8%), asymptomatic hematuria (11%), chronic renal disease (5.9%) and other diseases (11%). Cystatin C, creatinine, Schwartz estimated GFR and cystatin C estimated GFR (mean+/-SD) were 1.30+/-1.03 mg/dl, 0.82+/-1.20 mg/l, 143+/-72 ml/min/1.73 m(2) and 88+/-36 ml/min/1.73 m(2), respectively. Although GFR estimated by creatinine and cystatin C had a significant correlation, the Bland-Altman analysis showed greater differences between GFR estimated by the 2 methods, with a mean difference of 50 ml/min. Besides, >50% of the patients with a reduced cystatin C estimated GFR had a normal GFR when analyzed by the Schwartz formula. CONCLUSIONS: Our data shows that cystatin C-based GFR is more sensitive than previous study had demonstrated. It is important to perform studies in specific populations to determine the variability in GFR measurements.

Epidemia de dengue em Fortaleza, Ceará: inquérito soro-epidemiológico aleatório / Dengue epidemic in a Northeastern Brazil: random epidemiological serum survey

Seguindo-se à epidemia de dengue (DEN), em 1994, em Fortaleza, Ceará, causada pelo sorotipo 2 (DEN-2), realizou-se inquérito soro-epidemiológico aleatório para avaliar e dimensionar o impacto da mesma e a prevalência do dengue por distrito sanitário. Foi aplicado questionário contendo informaçöes gerais, condiçöes socio-econômicas, informaçöes sobre o quadro clínico e tempo de doença. A amostra foi calculada para estimar uma prevalência de 20 por cento, com erro relativo de 10 por cento, e intervalo de confiança de 95 por cento (erro a de 5 por cento). O sorteio e as análises foram realizadas por meio de computador usando programas apropriados. Foram colhidas 1.341 amostras de soro de 9 distritos sanitários, testadas por inibiçäo da hemaglutinaçäo, sendo classificadas como negativas e positivas (respostas primária - RP e secundária - RS). Foram reativas 588 (44 por cento) amostras, sendo 93 (7 por cento) RP e 495 (37 por cento) RS. A prevalência global em Fortaleza variou de 21 por cento a 71 por cento. Houve 41 por cento (243/588) de infecçöes assintomáticas (IA) e 59 por cento (346/588) sintomáticas (IS). Näo houve diferença da prevalência quanto ao sexo, faixa etária e escolaridade, ao contrário da condiçäo socioeconômica que apresentou diferenças estatisticamente significantes (p<0,001). Ocorreram mais IA (p<0,001) e IS (p<0,0001) em casos de RS que RP, com significância estatística em ambos os sexos. Os sintomas mais prevalentes nos casos confirmados foram febre, cefaléia, mialgias, exantema, mal estar geral, tontura e artralgias, sendo que prirido, dor ocular, exantema e gengivorragia foram estatisticamente significantes (p<0,005). Tontura e artralgias foram mais associados com RS que com RP, havendo diferenças estatísticas (p<0,05)