Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%).

To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD.

Between 2008 and 2018, consecutive patients with inconclusive stress test to detect CAD prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events(MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by stress echocardiography or nuclear stress testing with uncertain conclusion. To characterize this population, an unsupervised clustering analysis of these patients was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia in each of the clusters identified.

Of 1502 patients with inconclusive stress test (62±12 years, 59% men), 1397 (93%) completed the follow-up (median 5.5±2.3 years). Stress CMR was well tolerated without severe adverse event. An unsupervised clustering analysis of those patients identified 3 clusters:.

– Cluster 1 (n=524, 35%) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined by CMR, the lowest LVEF (35±7%) and the highest degree of LV dilatation.

– Cluster 2 (n=406, 27%) had the highest prevalence of previous CABG (82%), preserved LVEF(54±10%), absence of LV dilatation, and presence of myocardial scar(52%). This cluster comprised predominantly male patients (89%), with the highest rate of dyslipidemia(81%) or hypertension(71%).

– Cluster 3 (n=572, 38%) had the lowest rate of previous PCI/CABG (9%) and the lowest rate of myocardial scar in CMR(6%). This cluster gathered the oldest patients(73±11 years) and was predominantly female(60%) with the highest rate of atrial fibrillation(51%) or body mass index.

Survival analysis found significant differences across clusters for the occurrence of MACE (P=0.02). Moreover, the presence of inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, hazard ratio HR 2.28; [95% confidence interval CI: 1.31–3.99]; P=0.0028; cluster 2, HR 3.37; [95%CI, 1.97–5.75]; P<0.0001; cluster 3, HR 2.73; [95%CI, 1.67–4.46]; P<0.0001). In a multivariable Cox regression including clinical characteristics and CMR indexes, the presence of inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster (P<0.001 for all) (Fig. 1)

Cluster analysis of clinical and CMR variables identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict MACE.