Predictors of Total Mortality and Echocardiographic Response for Cardiac Resynchronization Therapy: A Cohort Study / Preditores de Mortalidade Total e de Resposta Ecocardiográfica à Terapia de Ressincronização Cardíaca: Um Estudo de Coorte

Abstract Background: Clinical studies demonstrate that up to 40% of patients do not respond to cardiac resynchronization therapy (CRT), thus, appropriate patient selection is critical to the success of CRT in heart failure. Objective: Evaluation of mortality predictors and response to CRT in the Brazilian scenario. Methods: Retrospective cohort study including patients submitted to CRT in a tertiary hospital in southern Brazil from 2008 to 2014. Survival was assessed through a database of the State Department of Health (RS). Predictors of echocardiographic response were evaluated using Poisson regression. Survival analysis was performed by Cox regression and Kaplan Meyer curves. A two-tailed p value less than 0.05 was considered statistically significant. Results: A total of 170 patients with an average follow-up of 1011 ± 632 days were included. The total mortality was 30%. The independent predictors of mortality were age (hazard ratio [HR] of 1.05, p = 0.027), previous acute myocardial infarction (AMI) (HR of 2.17, p = 0.049) and chronic obstructive pulmonary disease (COPD) (HR of 3.13, p = 0.015). The percentage of biventricular stimulation at 6 months was identified as protective factor of mortality ([HR] 0.97, p = 0.048). The independent predictors associated with the echocardiographic response were absence of mitral insufficiency, presence of left bundle branch block and percentage of biventricular stimulation. Conclusion: Mortality in patients submitted to CRT in a tertiary hospital was independently associated with age, presence of COPD and previous AMI. The percentage of biventricular pacing evaluated 6 months after resynchronizer implantation was independently associated with improved survival and echocardiographic response.

Resumo Fundamento: Estudos Clínicos demonstram que até 40% dos pacientes não respondem à terapia de ressincronização cardíaca (TRC), assim a seleção apropriada dos pacientes é fundamental para o sucesso da TRC na insuficiência cardíaca. Objetivo: Avaliação de preditores de mortalidade e resposta à TRC no cenário brasileiro. Métodos: Estudo de coorte retrospectivo incluindo os pacientes submetidos à TRC em hospital terciário no Sul do Brasil entre 2008-2014. A sobrevida foi avaliada através de banco de dados da Secretaria Estadual de Saúde (RS). Os preditores de resposta ecocardiográfica foram avaliados utilizando método de regressão de Poisson. A análise de sobrevida foi feita por regressão de Cox e curvas de Kaplan Meyer. Um valor de p bicaudal inferior a 0,05 foi considerado estatisticamente significativo. Resultados: Foram incluídos 170 pacientes com seguimento médio de 1011 ± 632 dias. A mortalidade total foi de 30%. Os preditores independentes de mortalidade identificados foram idade (hazzard ratio [HR] de 1,05; p = 0,027), infarto agudo do miocárdio (IAM) prévio (HR de 2,17; p = 0,049) e doença pulmonar obstrutiva crônica (DPOC) (HR de 3,13; p = 0,015). O percentual de estimulação biventricular em 6 meses foi identificado com fator protetor de mortalidade ([HR] 0,97; p = 0,048). Os preditores independentes associados à reposta ecocardiográfica foram ausência de insuficiência mitral, presença de bloqueio de ramo esquerdo e percentual de estimulação biventricular. Conclusão: A mortalidade nos pacientes submetidos à TRC em hospital terciário foi independentemente associada à idade, presença de DPOC e IAM prévio. O percentual de estimulação biventricular avaliado 6 meses após o implante do ressincronizador foi independentemente associado a melhora da sobrevida e resposta ecocardiográfica.

Complications after Surgical Procedures in Patients with Cardiac Implantable Electronic Devices: Results of a Prospective Registry / Complicações após Procedimentos Cirúrgicos em Portadores de Dispositivos Cardíacos Eletrônicos Implantáveis: Resultados de um Registro Prospectivo

Abstract Background: Complications after surgical procedures in patients with cardiac implantable electronic devices (CIED) are an emerging problem due to an increasing number of such procedures and aging of the population, which consequently increases the frequency of comorbidities. Objective: To identify the rates of postoperative complications, mortality, and hospital readmissions, and evaluate the risk factors for the occurrence of these events. Methods: Prospective and unicentric study that included all individuals undergoing CIED surgical procedures from February to August 2011. The patients were distributed by type of procedure into the following groups: initial implantations (cohort 1), generator exchange (cohort 2), and lead-related procedures (cohort 3). The outcomes were evaluated by an independent committee. Univariate and multivariate analyses assessed the risk factors, and the Kaplan-Meier method was used for survival analysis. Results: A total of 713 patients were included in the study and distributed as follows: 333 in cohort 1, 304 in cohort 2, and 76 in cohort 3. Postoperative complications were detected in 7.5%, 1.6%, and 11.8% of the patients in cohorts 1, 2, and 3, respectively (p = 0.014). During a 6-month follow-up, there were 58 (8.1%) deaths and 75 (10.5%) hospital readmissions. Predictors of hospital readmission included the use of implantable cardioverter-defibrillators (odds ratio [OR] = 4.2), functional class III­-IV (OR = 1.8), and warfarin administration (OR = 1.9). Predictors of mortality included age over 80 years (OR = 2.4), ventricular dysfunction (OR = 2.2), functional class III-IV (OR = 3.3), and warfarin administration (OR = 2.3). Conclusions: Postoperative complications, hospital readmissions, and deaths occurred frequently and were strongly related to the type of procedure performed, type of CIED, and severity of the patient's underlying heart disease.

Resumo Fundamento: Complicações após procedimentos cirúrgicos em portadores de dispositivos cardíacos eletrônicos implantáveis (DCEI) são um problema emergente devido ao aumento crescente na taxa destes procedimentos e ao envelhecimento da população, com consequente aumento de comorbidades. Objetivos: Identificar as taxas de complicações pós-operatórias, mortalidade e readmissão hospitalar, e pesquisar fatores de risco para a ocorrência desses eventos. Métodos: Registro prospectivo e unicêntrico que incluiu todos os indivíduos submetidos a procedimentos cirúrgicos em DCEI no período de fevereiro a agosto de 2011. Os pacientes foram distribuídos por tipos de procedimento nos seguintes grupos: implantes iniciais (coorte 1), troca de gerador (coorte 2) e procedimentos em cabos-eletrodos (coorte 3). Os desfechos foram avaliados por um comitê independente. Empregou-se a análise univariada e multivariada para a pesquisa de fatores de risco e o método de Kaplan-Meier para análise de sobrevida. Resultados: Foram incluídos 713 pacientes, sendo 333, 304 e 76 distribuídos nas coortes 1, 2 e 3, respectivamente. Complicações pós-operatórias foram detectadas em 7,5%, 1,6% e 11,8% dos pacientes nas coortes 1, 2 e 3, respectivamente (p = 0,014). Durante os 6 meses de seguimento, houve 58 (8,1%) óbitos e 75 (10,5%) readmissões hospitalares. Preditores de readmissão hospitalar incluíram o uso de cardioversor-desfibrilador implantável ( odds ratio [OR] = 4,2), classe funcional III-IV (OR = 1,8) e uso de warfarina (OR = 1,9). Preditores de mortalidade incluíram idade acima de 80 anos (OR = 2,4), disfunção ventricular (OR = 2,2), classe funcional III-IV (OR = 3,3) e uso de warfarina (OR = 2,3). Conclusões: Complicações pós-operatórias, readmissões hospitalares e óbitos foram frequentes. Esses eventos estiveram fortemente relacionados ao tipo de procedimento realizado, tipo de DCEI e gravidade da doença cardíaca do paciente.

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 / 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.

Mid-Term Outcomes in Patients Implanted with Cardiac Resynchronization Therapy

We applied cardiac resynchronization therapy (CRT) for desynchronized heart failure patients. We evaluated clinical outcomes including morbidity, mortality, and echocardiographic parameters in 47 patients with implanted CRT in Korea from October 2005 to May 2013. The combined outcomes of hospitalization from heart failure, heart transplantation and death were the primary end point. Median follow-up period was 17.5 months. The primary outcomes listed above occurred in 10 (21.3%) patients. Two patients (4.3%) died after CRT and 8 (17%) patients were hospitalized for recurrent heart failure. Among patients hospitalized for heart failure, 2 (4.3%) patients underwent heart transplantation. The overall free rate of heart failure requiring hospitalization was 90.1% (95% CI, 0.81-0.99) over one year and 69.4% (95% CI, 0.47-0.91) over 3 yr. We observed improvement of the New York Heart Association classification (3.1+/-0.5 to 1.7+/-0.4), decreases in QRS duration (169.1 to 146.9 ms), decreases in left ventricular (LV) end-diastolic (255.0 to 220.1 mL) and end-systolic (194.4 to 159.4 mL) volume and increases in LV ejection fraction (22.5% to 31.1%) at 6 months after CRT. CRT improved symptoms and echocardiographic parameters in a relatively short period, resulting in low mortality and a decrease in hospitalization due to heart failure.

Terapia de resincronización en pacientes con insuficiencia cardiaca: experiencia acumulada de 10 años / Cardiac resynchronization therapy in patients with heart failure: A 10-year experience

Background: Multiple randomized trials support the clinical benefits of cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and ventricular dyssynchrony. Since the year 2000 this therapy has been increasingly used in Chile. Aim: To describe the clinical characteristics and follow-up of HF patients undergoing CRT in a single Chilean university hospital during the last 10 years. Patients and Methods: All patients undergoing CRT between 2000 and 2010 in our university hospital were included. Clinical and echocardiographic data were extracted from medical records and mortality causes were obtained from the National Identification Service. Results: A total of 252 patients underwent CRT during the study period. Seventy five percent were in New York Heart Associatin (NYHA) functional class III and mean ejection fraction was 29 ± 10%. Complete left bundle branch block was present in 55% and 20% had permanent atrial fibrillation (AF). Mean survival was 86% at 1 year and 82% of patients in NYHA class III-IV improved at least one functional class. Survival was poorer in patients with ischemic etiology (hazard ratio (HR) 1.48), functional class IV (HR 2.2), right bundle branch block (RBBB) (HR 3.1) and AF (HR 3.4). No survival differences were observed between patients with and without an implanted cardiodefibrillator. Conclusions: This series show good clinical outcomes, comparable to those reported in randomized trials. Predictors of worse survival included an ischemic etiology, functional class IV, RBBB and AF. Patients with a defibrillator had no better survival, which could be relevant in countries with limited health care resources.