When Exercise ECG and Stress Echocardiography Disagree: Thoracic Geometry as a Potential Determinant of Exercise-Induced ST-Segment Abnormalities

Background: Exercise-induced ST-segment depression may occur despite negative exercise stress echocardiography (ESE) and absence of obstructive coronary artery disease (CAD), creating diagnostic uncertainty in symptomatic patients. Whether thoracic geometry contributes to this discordant response remains poorly understood. We investigated factors associated with a positive exercise ECG despite negative ESE (ECG+/ESE−), with particular focus on antero-posterior (A-P) thoracic diameter. Methods: In this prospective, single-center study, 101 consecutive symptomatic patients undergoing evaluation for suspected obstructive CAD were enrolled. ESE and coronary computed tomography angiography (CCTA) were prospectively planned in all patients. A positive exercise ECG was defined by horizontal/downsloping ST-segment depression ≥ 1.0 mm or upsloping depression ≥ 1.5 mm. ESE was considered negative in the absence of new or worsening regional wall-motion abnormalities. Patients with ECG+/ESE− and ECG−/ESE− responses were compared, and factors associated with ECG positivity were assessed by logistic regression. The discriminatory performance of A-P thoracic diameter was explored using ROC analysis. Results: All patients had negative ESE and no obstructive CAD on CCTA, while 35 (34.7%) developed a positive exercise ECG. Compared with ECG−/ESE− patients, those with ECG+/ESE− exhibited a smaller A-P thoracic diameter and higher modified Haller index, together with distinctive cardiac geometry and more frequent MVP. After multivariable adjustment, MVP was independently associated with ECG positivity (adjusted OR 8.50, 95% CI 1.07–67.75; p = 0.043), whereas increasing A-P thoracic diameter showed a strong inverse association (adjusted OR per 1-cm increase 0.026, 95% CI 0.005–0.143; p < 0.001). Smaller A-P thoracic diameter was also associated with lower exercise capacity and chronotropic response, greater exercise-induced ST-segment depression, and lower peak-exercise E/e′. A-P thoracic diameter showed excellent discrimination (AUC 0.962, 95% CI 0.921–1.000; p < 0.001); a data-derived cut-off ≤ 10.95 cm yielded 97.1% sensitivity and 93.9% specificity. Conclusions: MVP and reduced A-P thoracic diameter were independently associated with exercise ECG positivity despite negative ESE and absence of obstructive CAD, supporting a distinct thoraco-cardiac phenotype associated with exercise-induced repolarization abnormalities despite preserved LV contractile reserve. A-P thoracic diameter may provide complementary phenotypic information when exercise ECG and ESE findings are discordant; however, its incremental clinical value and the proposed ≤ 10.95-cm threshold require external validation.