The epidemiological characteristics and prognostic profiles of the population with CAD newly diagnosed are heterogeneous, particularly in terms of age, risk factors, degree of CAD burden and left ventricular abnormalities.

To identify patient subgroups by phenotypic unsupervised clustering integrating clinical data, CCTA and CMR parameters to unveil pathophysiological differences between subgroups of patients with CAD newly diagnosed.

Between 2008 and 2020, consecutive symptomatic patients without known CAD referred for CCTA were screened. Among those, patients with obstructive CAD (at least 1≥50% stenosis on CCTA) and referred for stress CMR were included and followed for MACE (CV death or nonfatal MI). A cluster analysis was performed on clinical, CCTA and CMR variables.

In total, 2015 patients (46.3% male, mean age 70±12years) completed the follow-up (median: 6.8 [IQR: 5.9–9.2] years). Three mutually exclusive phenogroups (PG) were identified: [PG1] older females without CV risk factor, without proximal stenosis by CCTA and preserved LVEF; [PG2] young females with several CV risk factors, with calcified stenosis by CCTA and preserved LVEF; and [PG3] young males with≥1 proximal significant stenosis without calcification by CCTA, myocardial scar and reduced LVEF. The occurrence of MACE (P<0.001), cardiovascular mortality (P<0.001) and all-cause mortality (P<0.001) differed among the three phenogroups. The PG3 presented the worse prognosis. In each phenogroup, inducible ischemia was associated with MACE (PG1, HR=3.09 [95% CI: 1.70–5.62]; PG2, HR: 3.62 [95% CI: 2.31–5.70]; PG3, HR: 3.55 [95% CI: 2.30–5.49]; all P<0.001) (Fig. 1).

Cluster analysis of clinical, CCTA and CMR variables identified 3 phenogroups of patients with CAD newly diagnosed that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup.