BACKGROUND: Psychosocial stress could contribute to cardiovascular disease including mental stress-induced myocardial ischaemia (MSIMI), especially in young and midlife women. Diagnosis of MSIMI remains still enigma for physicians, and is rarely reported in patients with symptoms but nonobstructive coronary arteries. CASE SUMMARY: A 40-year-old female bus driver suffered from refractory angina despite medical treatment over the past six months. Invasive angiography showed merely 40% stenosis in the middle segment of the left anterior descending artery while coronary spasm was also suspected. Mental stress assessment was conducted given her psychosocial adversities in the past few years and high scores during the psychological scale evaluation. The patient reported aggravated chest pain during mental stress testing. Apical perfusion delay (∼4 s) in replenishment following high-mechanical index flash impulses was simultaneously observed on myocardial contrast echocardiography, along with hypokinetic apical wall motion. A reduced left ventricular ejection fraction (42%) compared to admission (62%) was also noted, and left ventricular global longitudinal strain was -17.1% (normal value <
-20%). Reactive hyperaemia index reflecting peripheral microvascular function showed mild decline. The patient was diagnosed with MSIMI on positron emission tomography (PET) and effectively treated with escitalopram. DISCUSSION: Mental stress-induced myocardial ischaemia could coexist with nonobstructive coronary artery disease due to their similar pathological basis of coronary microcirculation. The crucial role of echocardiography with contrast agent in MSIMI diagnosis was emphasized in the present case and confirmed on PET. Comprehensive management including pharmacotherapy specific for psychosocial disorders was proved effective that significantly improved the patient prognosis.