Relationship between changing patient-reported outcomes and subsequent clinical events in patients with chronic heart failure: insights from HF-ACTION

Abstract

Aims: A 5-point change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) is commonly considered to be a clinically significant difference in health status in patients with heart failure. We evaluated how the magnitude of change relates to subsequent clinical outcomes.

Methods and results: Using data from the HF-ACTION trial of exercise training in chronic heart failure (n = 2331), we used multivariable Cox regression with piecewise linear splines to examine the relationship between change in KCCQ overall summary score from baseline to 3 months (range 0-100; higher scores reflect better health status) and subsequent all-cause mortality/hospitalization. Among 2038 patients with KCCQ data at the 3-month visit, KCCQ scores increased from baseline by ≥5 points for 45%, scores decreased by ≥5 points for 23%, and scores changed by <5 points for the remaining 32% of patients. There was a non-linear relationship between change in KCCQ and outcomes. Worsening health status was associated with increased all-cause mortality/hospitalization (adjusted hazard ratio 1.07 per 5-point KCCQ decline; 95% confidence interval 1.03-1.12; P < 0.001). In contrast, improving health status, up to an 8-point increase in KCCQ, was associated with decreased all-cause mortality/hospitalization (adjusted hazard ratio 0.93 per 5-point increase; 95% confidence interval 0.90-0.97; P < 0.001). Additional improvements in health status beyond an 8-point increase in KCCQ was not associated with all-cause death or hospitalization (P = 0.42).

Conclusion: In patients with heart failure, small changes in KCCQ are associated with changing future risk, but more research will be necessary to understand how different magnitudes of improving health status affect outcomes.

Trial registration: ClinicalTrials.gov NCT00047437.

Keywords: Health status; Patient-reported outcomes; Quality of life.

Figure 1:. Distributions of KCCQ in Analysis Cohort

Panel A shows the distribution of patients’ Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 3 months in the analysis population. The median baseline KCCQ overall summary score was 69 (Q1, Q3; 52, 83). Panel B shows the distribution of patient’s change in KCCQ overall summary score from baseline to 3 months. As represented by the figure, 918 patients (45%) experienced a ≥5 point improvement in health status, while 23% (N=462) experienced a ≥5 point decline, and 32% (N=658) experienced a change of less than 5 points. Overall, 215 (11%) patients experienced a change between +5 to +8 KCCQ points and 703 (35%) patients experienced an improvement in KCCQ overall score above 8 points.

Figure 2:. Kaplan-Meier Curves of All-Cause Mortality or Hospitalization, All-Cause Mortality, and Cardiovascular Death or Heart Failure Hospitalization

Unadjusted Kaplan-Meier curves for all-cause mortality or hospitalization (A), all-cause mortality (B), and cardiovascular mortality or heart failure hospitalization (C) in patients event-free for at least 3 months, stratified by changing Kansas City Cardiomyopathy Questionnaire overall summary score between baseline and 3 months. Blue line indicates ≥ 5 point decline; Red line indicates change within 5 points; Green line indicates ≥ 5 point increase.

Figure 3:. Relationship between Change in KCCQ at 3 Months and All-cause Mortality or Hospitalization

Among patients event-free at 3 months, this plot demonstrates the nonlinear relationship between 3-month change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score and predicted probability of all-cause death or hospitalization within 3 years. In our data, we observe a single inflection point where change in KCCQ is equal to 8. Increases in KCCQ from 0 to 8 was associated with a significant reduction in risk (p<0.001) but increases in KCCQ greater than 8 were not significantly associated with an increase in risk (p=0.183). Vertical reference bars identify these inflection points. Decreases in KCCQ between baseline and 3 months was associated with increased risk (p <0.001). Solid line indicates the predicted probability of death/hospitalization; dotted lines indicates point-wise 95% confidence intervals.