Unravelling the grey zone: submaximal-to-peak stress echocardiography enhances diagnostic accuracy in differentiating early dilated cardiomyopathy from physiological adaptation

BACKGROUND: Participation in regular endurance exercise may be associated with physiological left ventricular (LV) dilatation and concomitant low resting LV ejection fraction (LVEF), a phenotype indistinguishable from early dilated cardiomyopathy (DCM) on resting imaging alone and termed the "grey zone". Stress echocardiography has emerged as a potential arbiter and has been proposed to resolve this dilemma. OBJECTIVES: We evaluated the diagnostic accuracy of stress echocardiography in distinguishing physiological from pathological LV dilatation and assessed whether incorporating submaximal-to-peak contractile reserve improved discriminatory value in athletes in the grey zone. METHODS: Of the 182 athletic individuals, 62 control athletes with an enlarged LV and normal LVEF, 58 athletic DCM individuals, and 62 grey zone athletes underwent stress echocardiography using a semi-supine bicycle. In addition to the ability to augment LVEF ≥ 10% from rest to maximal exercise, we evaluated the ability to augment LVEF from submaximal exercise (80% of maximal heart rate) to peak exercise. RESULTS: Resting LV dimensions did not differ significantly amongst the groups. Control athletes had higher resting LVEF than grey zone athletes and DCM individuals (62.1% vs 52.1% and 53.1%; p=<0.001). Control and grey zone athletes showed greater ΔLVEF from rest to peak exercise than DCM individuals (21% and 19.2% vs 4.9%; p < 0.001). Most control (98.3%) and grey-zone athletes (90.3%) achieved a ΔLVEF ≥ 10% from rest to peak exercise compared with 20.6% of athletic DCM individuals. Control and grey zone athletes also revealed a mean increase in LVEF from submaximal to peak exercise of 7.5% and 3.8%, respectively, whereas DCM individuals showed a mean LVEF decline of -4.3% (p < 0.001). Although 20.6% of DCM individuals demonstrated a ΔLVEF ≥ 10% from rest to peak, only a single DCM individual augmented LVEF from submaximal to peak exercise. Failure to increase LVEF ≥ 10% from rest to peak exercise identified DCM with 79.4% sensitivity and 98.3% specificity. Combining this inability with a failure to augment LVEF from submaximal to peak exercise improved the sensitivity to 98.2% and specificity to 98.4%. CONCLUSION: Reliance on rest-to-peak augmentation of ≥10% alone risks misclassification. Introducing submaximal-to-peak augmentation enhances diagnostic precision by identifying virtually all individuals with DCM while preserving specificity.