Prediction of 2-year major adverse cardiac events from myocardial perfusion scintigraphy and clinical risk factors

Abstract

Background

We developed CRAX2MACE, a new tool derived from clinical and SPECT myocardial perfusion imaging (MPI) variables, to predict 2-year probability of major adverse cardiac event (MACE) comprising death, hospitalized acute myocardial infarction or coronary revascularization.

Methods

Consecutive individuals with SPECT MPI 2001-2008 had two-year MACE determined from population-based health services data. CRAX2MACE included age, sex, diabetes, recent cardiac hospitalization, pharmacologic stress, stress total perfusion deficit (TPD), ischemic (stress-rest) TPD, left ventricular ejection fraction and transient ischemic dilation ratio. Two-year event rates were classified as low (< 5%), moderate (5.0-9.9%), high (10-19.9%) and very high (20% or greater).

Results

The study population comprised 3896 individuals for the development and 1946 for the validation subgroups with subsequent MACE in 589 (15.1%) and 272 (14.0%), respectively. CRAX2MACE, derived from the development subgroups, accurately stratified MACE risk in the validation subgroup (area under the receiver operating characteristics curve 0.79) with stepwise increase in the observed event rate with increasing predicted risk category (low, 2.3%; moderate, 5.5%; high, 18.8%; very high 33.2%; P-trend < 0.001).

Conclusions

A simple tool based upon clinical risk factors and MPI variables predicts 2-year cardiac events. Risk stratification between the low and very high groups was greater than tenfold.

Introduction

Coronary artery disease (CAD) remains the principle cause of death in developed countries despite major advances in both the medical and interventional approaches to management, with an emerging epidemic among low- and middle-income countries which are now responsible for overwhelming majority of cardiovascular disease worldwide.^1,2 Myocardial perfusion imaging (MPI) is a powerful technique to assess for the presence and severity of CAD, and is predictive of both short-term and long-term cardiac events.³, Clinical risk factors and derived composite scores are also widely used to stratify risk for CAD and related outcomes.⁴ To date, there have been limited attempts to quantitatively integrate MPI and clinical risk factors into a unified risk measure that could potentially be used to generate a personalized risk profile and guide treatment, although several prognostic risk models have been developed and adopted for non-MPI laboratory and imaging measures.⁵

There is increasing consensus that therapeutic intervention should be personalized based upon an individual’s level of risk and anticipated benefit.6, 7, 8 An accurate assessment of baseline risk is therefore an essential component of this process. A previous study provided proof-of-concept that a prediction tool, CRAX, for five-year death and 5-year acute myocardial infarction (AMI) based upon fully automated MPI analysis and clinical risk factors was feasible.⁹ Limitations of CRAX included the relatively long time horizon of 5 years. Moreover, diabetes was not included in this model though studies document the importance of diabetes as an important risk factor for adverse cardiac outcomes even when adjusted for MPI variables, and as a CAD equivalent.10, 11, 12

The objective of the current analysis was to develop a new clinical prediction tool, CRAX2MACE, to predict 2-year probability of major adverse cardiac event (MACE) that comprised death, hospitalized AMI or coronary revascularization. Clinical risk factors and MPI variables were included in the prediction algorithm which was developed and internally validated in a large clinical cohort.