Exercise for Systolic HF in Relation to Disease Severity
Exercise for Systolic HF in Relation to Disease Severity
Background This post hoc analysis of the HF-ACTION cohort explores the primary and secondary results of the HF-ACTION study by etiology and severity of illness.
Methods HF-ACTION randomized stable outpatients with reduced left ventricular (LV) function and heart failure (HF) symptoms to either supervised exercise training plus usual care or to usual care alone. The primary outcome was all-cause mortality or all-cause hospitalization; secondary outcomes included all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or HF hospitalization. The interaction between treatment and risk variable, etiology or severity as determined by risk score, New York Heart Association class, and duration of cardiopulmonary exercise test was examined in a Cox proportional hazards model for all clinical end points.
Results There was no interaction between etiology and treatment for the primary outcome (P = .73), cardiovascular (CV) mortality or CV hospitalization (P = .59), or CV mortality or HF hospitalization (P = .07). There was a significant interaction between etiology and treatment for the outcome of mortality (P = .03), but the interaction was no longer significant when adjusted for HF-ACTION adjustment model predictors (P = .08). There was no significant interaction between treatment effect and severity, except a significant interaction between cardiopulmonary exercise duration and training was identified for the primary outcome of all-cause mortality or all-cause hospitalization.
Conclusion Consideration of symptomatic (New York Heart Association classes II to IV) patients with HF with reduced LV function for participation in an exercise training program should be made independent of the cause of HF or the severity of the symptoms.
Heart failure (HF) with reduced left ventricular (LV) function affects a large patient population that is characterized by heterogeneity. Characteristics such as etiology (ischemic vs nonischemic), exercise tolerance, and severity (ie, New York Heart Association [NYHA] class) of illness are independent risk factors for outcomes. Therapies for patients with HF will occasionally target certain subgroups of patients based on the mechanism of the therapy and/or the differential risk within the subgroups. For example, the implantable cardioverter defibrillator was initially evaluated in subjects with ischemic cardiomyopathy due to the higher risk of ventricular arrhythmias and sudden cardiac death in this subgroup. Implantable cardioverter defibrillator indications did expand to include nonischemic patients when larger populations were evaluated and the therapy was identified to have a greater impact in NYHA class II patients versus class III patients.
HF-ACTION was a randomized controlled trial evaluating an exercise training (ET) program plus usual care versus usual care (UC) alone in HF subjects with reduced LV function. The HF-ACTION study stratified randomization by etiology based on studies showing a differential effect of ET in patients with HF by etiology and evidence demonstrating the clinical benefit of ET in patients with coronary artery disease (CAD). Subsequent to the initiation of the study, a meta-analysis of ET trials enrolling patients with HF with reduced LV function identified a nonsignificant differential response by etiology (hazard ratio [HR] [95% CI] 0.54 [0.35–0.83] vs 0.93 [0.52–1.68], ischemic vs nonischemic, P = .10 for the interaction).
HF-ACTION identified a modest benefit of ET on the primary outcome of all-cause mortality or all-cause hospitalization after adjusting for 4 significant predictors of the outcome. One of these independent predictors was exercise duration during the cardiopulmonary exercise (CPX) test, an indicator of HF severity. There was a nonsignificant difference in the primary outcome for participants based on NYHA class (HR [95% CI], NYHA II 0.95 [0.83–1.08], NYHA III/IV 0.85 [0.73–1.00], P value for interaction = .27). In addition, there was no difference in HR between ischemic and nonischemic etiology (HR [95% CI], ischemic 0.94 [0.82–1.08], non ischemic 0.91 [0.78–1.05], P value for interaction = .73).
The current post hoc analysis of the HF-ACTION cohort further explores the primary and secondary results of the HF-ACTION study by etiology and severity of illness. We hypothesized that differences in the primary outcome and key secondary outcomes, particularly disease-specific outcomes such as HF hospitalization, would exist between subgroups when stratified by etiology or severity of illness.
Abstract and Introduction
Abstract
Background This post hoc analysis of the HF-ACTION cohort explores the primary and secondary results of the HF-ACTION study by etiology and severity of illness.
Methods HF-ACTION randomized stable outpatients with reduced left ventricular (LV) function and heart failure (HF) symptoms to either supervised exercise training plus usual care or to usual care alone. The primary outcome was all-cause mortality or all-cause hospitalization; secondary outcomes included all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or HF hospitalization. The interaction between treatment and risk variable, etiology or severity as determined by risk score, New York Heart Association class, and duration of cardiopulmonary exercise test was examined in a Cox proportional hazards model for all clinical end points.
Results There was no interaction between etiology and treatment for the primary outcome (P = .73), cardiovascular (CV) mortality or CV hospitalization (P = .59), or CV mortality or HF hospitalization (P = .07). There was a significant interaction between etiology and treatment for the outcome of mortality (P = .03), but the interaction was no longer significant when adjusted for HF-ACTION adjustment model predictors (P = .08). There was no significant interaction between treatment effect and severity, except a significant interaction between cardiopulmonary exercise duration and training was identified for the primary outcome of all-cause mortality or all-cause hospitalization.
Conclusion Consideration of symptomatic (New York Heart Association classes II to IV) patients with HF with reduced LV function for participation in an exercise training program should be made independent of the cause of HF or the severity of the symptoms.
Introduction
Heart failure (HF) with reduced left ventricular (LV) function affects a large patient population that is characterized by heterogeneity. Characteristics such as etiology (ischemic vs nonischemic), exercise tolerance, and severity (ie, New York Heart Association [NYHA] class) of illness are independent risk factors for outcomes. Therapies for patients with HF will occasionally target certain subgroups of patients based on the mechanism of the therapy and/or the differential risk within the subgroups. For example, the implantable cardioverter defibrillator was initially evaluated in subjects with ischemic cardiomyopathy due to the higher risk of ventricular arrhythmias and sudden cardiac death in this subgroup. Implantable cardioverter defibrillator indications did expand to include nonischemic patients when larger populations were evaluated and the therapy was identified to have a greater impact in NYHA class II patients versus class III patients.
HF-ACTION was a randomized controlled trial evaluating an exercise training (ET) program plus usual care versus usual care (UC) alone in HF subjects with reduced LV function. The HF-ACTION study stratified randomization by etiology based on studies showing a differential effect of ET in patients with HF by etiology and evidence demonstrating the clinical benefit of ET in patients with coronary artery disease (CAD). Subsequent to the initiation of the study, a meta-analysis of ET trials enrolling patients with HF with reduced LV function identified a nonsignificant differential response by etiology (hazard ratio [HR] [95% CI] 0.54 [0.35–0.83] vs 0.93 [0.52–1.68], ischemic vs nonischemic, P = .10 for the interaction).
HF-ACTION identified a modest benefit of ET on the primary outcome of all-cause mortality or all-cause hospitalization after adjusting for 4 significant predictors of the outcome. One of these independent predictors was exercise duration during the cardiopulmonary exercise (CPX) test, an indicator of HF severity. There was a nonsignificant difference in the primary outcome for participants based on NYHA class (HR [95% CI], NYHA II 0.95 [0.83–1.08], NYHA III/IV 0.85 [0.73–1.00], P value for interaction = .27). In addition, there was no difference in HR between ischemic and nonischemic etiology (HR [95% CI], ischemic 0.94 [0.82–1.08], non ischemic 0.91 [0.78–1.05], P value for interaction = .73).
The current post hoc analysis of the HF-ACTION cohort further explores the primary and secondary results of the HF-ACTION study by etiology and severity of illness. We hypothesized that differences in the primary outcome and key secondary outcomes, particularly disease-specific outcomes such as HF hospitalization, would exist between subgroups when stratified by etiology or severity of illness.
