P atients with cardiac syndrome X (CSX)-typical chest pain and electrocardiographic changes suggestive of myocardial ischemia despite normal coronary arteriograms-represent a diagnostic and therapeutic riddle. CSX is not associated with an increased mortality or an increased risk of cardiovascular events, but it often severely impairs quality of life and represents a substantial cost burden to the healthcare system. This syndrome of chest pain with normal coronary arteries encompasses a variety of pathogenic subgroups and is predominantly seen in postmenopausal women. Lack of understanding of the syndrome by the cardiovascular physician not infrequently results in discounting the clinical problem. Treatment remains elusive, but management strategies can improve the patient's quality of life and reduce the financial burden imposed on health services.Case Report: A 55-year-old white female pharmacist underwent diagnostic coronary arteriography for the assessment of typical exertional chest pain, which had started 18 months previously and had gradually become more frequent and severe despite treatment with oral and sublingual nitrates and atenolol (50 mg daily). Central chest pain and dyspnea occurred at rest and with emotional stress and responded rather poorly to sublingual nitrate administration. ECG exercise stress test was positive (Figure 1), and transient perfusion defects were found on thallium-201 dipyridamole testing ( Figure 2). She had long-lasting excruciating chest pain after dipyridamole infusion. Risk factors included a family history of coronary artery disease, a lowdensity lipoprotein-cholesterol level of 4.2 mmol/L, a high-density lipoproteincholesterol level 0.9 mmol/L, menopausal status, a previous history of smoking, body-mass index of 28 kg/m 2 , and raised high-sensitivity C-reactive protein levels (3.8 mg/L). Coronary arteries and left ventricular function were completely normal. Coronary intravascular ultrasound showed no significant subangiographic disease. After reassurance by her cardiologist, all cardiac medications were discontinued. Symptoms continued to deteriorate over the ensuing months, however, to the point that she was unable to work and required help with her supermarket shopping and household tasks. She was referred to our CSX clinic for treatment.Esophageal manometry and pH measurements showed 4 asymptomatic episodes of gastroesophageal reflux without associated ECG changes. Specialist psychological assessment revealed no abnormalities. Coronary artery spasm and musculoskeletal conditions were ruled out as the cause of her symptoms. Transient ST-segment depression and chest pain detected during ambulatory monitoring were usually associated with tachycardia ( Figure 3). It was noted that 20% of the episodes of ST-segment depression occurred with a heart rate Ͻ80 bpm. Brachial artery flow-mediated dilatation was reduced to 1.3%, indicating systemic endothelial dysfunction. Dobutamine stressechocardiogram showed no regional wall motion abnormalities despite the occurrence of ST...