Negative exercise stress echocardiography and long-term outcomes: insights from a retrospective cohort study

Exercise stress echocardiography (ESE) is widely used to detect inducible myocardial ischaemia. However, a substantial proportion of ESEs remains inconclusive or shows abnormal non-ischaemic findings (fixed regional wall motion abnormalities without new inducible ischaemia), often requiring further testing. Baseline characteristics differ markedly between these groups, highlighting the need for studies that precisely adjust for confounders.This article aims to assess long-term outcomes among patients with negative, non-diagnostic or abnormal non-ischaemic ESE using robust confounder adjusted analyses.

This was a retrospective cohort study conducted between 2017 and 2023 at a tertiary care hospital in Santander, northern Spain. Patients with inducible ischaemia or non-treadmill protocols were excluded. Participants were classified as diagnostic negative (≥85% predicted heart rate), non-diagnostic negative (<85%) or abnormal non-ischaemic (fixed wall motion abnormalities without inducible ischaemia). The primary endpoint was a composite of all-cause mortality, cardiovascular death, ischaemic hospitalisation and coronary angiography. Inverse probability of treatment weighting (IPTW) and generalised pairwise comparisons (GPC) assessed outcomes.

During a mean follow-up of 71 months among 788 patients, the overall event rate was 3.2 per 100 patient-years. Adjusted Cox models showed no significant differences between non-diagnostic (HR 0.92; 95% CI 0.49 to 1.72) or abnormal non-ischaemic (HR 0.80; 95% CI 0.24 to 2.61) versus diagnostic negative groups. Independent risk predictors included type 2 diabetes mellitus (HR 2.13; 95% CI 1.13 to 4.03) and lower ejection fraction (HR 0.97 per 1% increase; 95% CI 0.94 to 0.99). GPC identified more angiographies in the negative non-diagnostic group (p=0.04) and greater mortality in the abnormal non-ischaemic group (p=0.02) than in diagnostic negative patients, despite similar composite outcomes.

Negative ESE generally predicts low risk; however, non-diagnostic or abnormal non-ischaemic GPC findings show subtle prognostic differences undetected by conventional analysis. These subgroups may warrant closer follow-up or additional imaging.