Stress cardiac magnetic resonance imaging provides effective cardiac risk reclassification in patients with known or suspected stable coronary artery disease

Abstract

Background: A recent large-scale clinical trial found that an initial invasive strategy does not improve cardiac outcomes beyond optimized medical therapy in patients with stable coronary artery disease. Novel methods to stratify at-risk patients may refine therapeutic decisions to improve outcomes.

Methods and results: In a cohort of 815 consecutive patients referred for evaluation of myocardial ischemia, we determined the net reclassification improvement of the risk of cardiac death or nonfatal myocardial infarction (major adverse cardiac events) incremental to clinical risk models, using guideline-based low (<1%), moderate (1% to 3%), and high (>3%) annual risk categories. In the whole cohort, inducible ischemia demonstrated a strong association with major adverse cardiac events (hazard ratio=14.66; P<0.0001) with low negative event rates of major adverse cardiac events and cardiac death (0.6% and 0.4%, respectively). This prognostic robustness was maintained in patients with previous coronary artery disease (hazard ratio=8.17; P<0.0001; 1.3% and 0.6%, respectively). Adding inducible ischemia to the multivariable clinical risk model (adjusted for age and previous coronary artery disease) improved discrimination of major adverse cardiac events (C statistic, 0.81-0.86; P=0.04; adjusted hazard ratio=7.37; P<0.0001) and reclassified 91.5% of patients at moderate pretest risk (65.7% to low risk; 25.8% to high risk) with corresponding changes in the observed event rates (0.3%/y and 4.9%/y for low and high risk posttest, respectively). Categorical net reclassification index was 0.229 (95% confidence interval, 0.063-0.391). Continuous net reclassification improvement was 1.11 (95% confidence interval, 0.81-1.39).

Conclusions: Stress cardiac magnetic resonance imaging effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at moderate to high pretest clinical risk and in patients with previous coronary artery disease.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT01821924.

Keywords: chronic ischemia; magnetic resonance imaging.

Conflict of interest statement

Conflict of Interest Disclosures: Dr. Kwong is supported by a NIH grant R01-HL091157 and a research grant from Astellas Pharmaceuticals. All other authors have no financial disclosures relevant to the content of this manuscript.

Figures

Figure 1

Kaplan-Meier MACE-free survival curves for the whole cohort (left upper panel) and patients with prior CAD (right upper panel). Follow-up period was truncated to 8 years. The bottom panels display the corresponding cumulative hazard function for illustration of rates of MACE accumulation in these respective patient groups during the first 5 years after stress CMR assessment. P-value was derived using the log-rank test. Abbreviations: ISCH = inducible ischemia by stress CMR.

Figure 2

Kaplan-Meier all cause mortality-free survival curves for the whole cohort (A) and patients with prior CAD (B). Follow-up period was truncated to 8 years. P-value was derived using the log-rank test. Abbreviations: ISCH = inducible ischemia by stress CMR.

Figure 3

Annualized event rates of MACE (A), cardiac death (B), and all-cause mortality (C) in the whole cohort and stratified by the presence (red) or absence (blue) of inducible ischemia. Comparison P-values were calculated by chi-square tests.

Figure 3

Annualized event rates of MACE (A), cardiac death (B), and all-cause mortality (C) in the whole cohort and stratified by the presence (red) or absence (blue) of inducible ischemia. Comparison P-values were calculated by chi-square tests.

Figure 3

Annualized event rates of MACE (A), cardiac death (B), and all-cause mortality (C) in the whole cohort and stratified by the presence (red) or absence (blue) of inducible ischemia. Comparison P-values were calculated by chi-square tests.

Figure 4

Risk reclassification improvement. Presence of inducible ischemia was added to the multivariable clinical risk model (Model 1 in Table 3) for risk reclassification across ACC/AHA practice guideline categories. Pie charts demonstrate proportion of patients reclassified by the addition of inducible ischemia across pre-test risk categories. Observed annualized rates of MACE for reclassified patients were displayed in bar graphs.