Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score: Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction

Abstract

Background The Meta-Analysis Global Group in Chronic Heart Failure ( MAGGIC ) mortality risk score, derived from a large sample of patients with heart failure ( HF ) across the spectrum of ejection fraction ( EF ), has not yet been externally validated in a well-characterized HF with preserved EF cohort with adjudicated morbidity outcomes. Methods and Results We evaluated the MAGGIC risk score (composed of 13 clinical variables) in 407 patients with HF with preserved EF enrolled in a prospective registry and used Cox regression to evaluate its association with morbidity/mortality. We used receiver-operating characteristic analysis to compare the predictive ability of the MAGGIC risk score with the more complex Seattle Heart Failure Model, and we determined the value of adding B-type natriuretic peptide to the MAGGIC risk score for risk prediction. During a mean follow-up time of 3.6±1.8 years, 28% died, 32% were hospitalized for HF , and 55% had a cardiovascular hospitalization and/or death. The MAGGIC score, a mean± SD of 18±7, was significantly associated with mortality ( P<0.0001), HF hospitalizations ( P<0.0001), and the combined end point of cardiovascular-related hospitalizations or death (hazard ratio, 1.8 [95% confidence interval, 1.6-2.1], per 1- SD increase in the MAGGIC score; P<0.0001). Receiver-operating characteristic analyses showed that MAGGIC and Seattle Heart Failure Model performed similarly in predicting HF with preserved EF outcomes, but the MAGGIC score demonstrated better calibration for hospitalization outcomes. Further analyses showed that B-type natriuretic peptide was additive to the MAGGIC risk score for predicting outcomes ( P<0.01 by likelihood ratio test). Conclusions The MAGGIC risk score is a simple, yet powerful method of risk stratification for both morbidity and mortality in HF with preserved EF . Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01030991.

Keywords: heart failure; morbidity; mortality; risk assessment.

Figure 1

A, Relative contributions of individual predictor variables in the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) to total MAGGIC integer risk score. B, Histogram of MAGGIC integer risk scores in the cohort with heart failure with preserved ejection fraction (HFpEF). A, To put all of the MAGGIC risk score component variables on a single graph, each continuous variable that was a component of the risk score (age, creatinine, systolic blood pressure, New York Heart Association [NYHA] class, and body mass index) was standardized to a mean of 0 and an SD of ±1. All other components of the score (ie, categorical variables) were added together, and this summary variable was also standardized to a mean of 0 and an SD of ±1. Next, locally weighted smoothed scatterplots of each of the MAGGIC risk score predictors were plotted against the overall risk score to show the relative contribution of high and low values of the risk score components to the overall MAGGIC risk score. B, The distribution of MAGGIC integer risk scores for all 407 patients in the cohort with HFpEF shows a nearly bell‐shaped curve with a mean score of 20±6.

Figure 2

Kaplan‐Meier curves of event‐free survival stratified by tertiles of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. The MAGGIC risk score was significantly associated with mortality and with each of the clinical morbidity end points, including cardiovascular‐related hospitalization, heart failure (HF) hospitalization, and the combined end point of cardiovascular (CV) hospitalization and mortality (log‐rank P<0.001 for all survival curves). MAGGIC risk scores per tertile: tertile 1, 2 to 13; tertile 2, 14 to 20; and tertile 3, 21 to 38.

Figure 3

Cumulative incidence function curves of event‐free survival stratified by tertiles of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. The MAGGIC risk score was significantly associated with mortality and with each of the clinical morbidity end points, including cardiovascular (CV) related hospitalization, heart failure (HF) hospitalization, and the combined end point of cardiovascular hospitalization and mortality (P<0.001 for all cumulative incidence curves). MAGGIC risk scores per tertile: tertile 1, 2 to 13; tertile 2, 14 to 20; and tertile 3, 21 to 38.

Figure 4

Calibration plots for the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score (predicted vs actual probabilities). CV indicates cardiovascular; HF, heart failure.

Figure 5

Calibration plots for the Seattle Heart Failure Model (SHFM) risk score (predicted vs actual probabilities). CV indicates cardiovascular; HF, heart failure.

Figure 6

Event‐free survival rates of patients with heart failure with preserved ejection fraction stratified according to median Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score and B‐type natriuretic peptide (BNP) value. BNP is additive to the MAGGIC risk score on the basis of stratification of patients by median MAGGIC and BNP scores. Log‐rank P<0.001 for the entire survival curve. On Cox proportional hazards analysis, each of the 4 strata is statistically significantly different from the others (P<0.05), except for the comparison of the middle 2 groups (P=0.076). CV indicates cardiovascular.