Clustering of patients with inconclusive non-invasive stress testing referred for vasodilator stress cardiovascular magnetic resonance

Abstract

BackgroundInconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods. AimsTo identify patient subgroups by phenotypic unsupervised clustering, integrating clinical and cardiovascular magnetic resonance data to unveil pathophysiological differences between subgroups of patients with inconclusive stress tests. MethodsBetween 2008 and 2020, consecutive patients with a first inconclusive non-invasive stress test referred for stress cardiovascular magnetic resonance were followed for the occurrence of major adverse cardiovascular events (defined as cardiovascular death or myocardial infarction). A cluster analysis was performed on clinical and cardiovascular magnetic resonance variables. ResultsOf 1402 patients (67% male; mean age 70±11years) who completed the follow-up (median 6.5years, interquartile range 5.6–7.5years), 197 experienced major adverse cardiovascular events (14.1%). Three distinct phenogroups were identified based upon unsupervised hierarchical clustering of principal components: phenogroup 1=history of percutaneous coronary intervention with viable myocardial infarction and preserved left ventricular ejection fraction; phenogroup 2=atrial fibrillation with preserved left ventricular ejection fraction; and phenogroup 3=coronary artery bypass graft with non-viable myocardial scar and reduced left ventricular ejection fraction. Using survival analysis, the occurrence of major adverse cardiovascular events (P=0.007), cardiovascular mortality (P=0.002) and all-cause mortality (P<0.001) differed among the three phenogroups. Phenogroup 3 presented the worse prognosis. In each phenogroup, ischaemia was associated with major adverse cardiovascular events (phenogroup 1: hazard ratio 2.79, 95% confidence interval 1.61–4.84; phenogroup 2: hazard ratio 2.59, 95% confidence interval 1.69–3.97; phenogroup 3: hazard ratio 3.16, 95% confidence interval 1.82–5.49; all P<0.001). ConclusionsCluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.