Syndrome X

Opinion Statement

• Syndrome X, defined as typical angina with positive exercise test results and normal coronary angiographic findings, represents a multifactorial pathophysiologic state that may range from abnormalities in pain perception to abnormalities in endothelial- and nonendothelial-dependent coronary flow reserve associated with myocardial ischemia. Treatment begins with accurate diagnosis by means of a comprehensive coronary vascular reactivity evaluation. This may lay the groundwork for appropriate treatment.

• The management of patients with syndrome X is challenging, and it may be necessary to attempt various medications depending on the patient’s response. We feel that the first step in the treatment is accurate diagnosis. This is done by performing a functional angiogram (assessment of endothelial-dependent and endothelialindependent coronary flow reserve). In those without evidence of coronary flow reserve abnormalities, reassurance might be curative; however, in those who continue to have symptoms, a trial of imipramine therapy at a dose of 50 mg/d may be attempted, provided other organic disorders (in particular gastrointestinal disorders) are excluded.

• Those who demonstrate evidence of abnormal coronary vascular reactivity are approached as outlined in Figure 1. Patients are advised to avoid medications that may cause coronary “spasm.” We routinely refer our patients to the cardiovascular health clinic for risk factor management and an exercise program.

• Our first choice of medications usually consists of slow-release calcium channel blockers. We tend to start with a once-a-day regimen, and based on the response, we occasionally change the regimen to twice a day. If the functional angiogram reveals concomitant epicardial disease, then nitrates are added to the medical regimen. Angiotensin-converting enzyme inhibitors are part of the treatment if the patient has hypertension or diabetes or if calcium channel blocker therapy fails. L-Arginine at an initial dosage of 1 g three times daily is added and may be increased to 3 g three times daily if no contraindications are present. Because there are no data regarding the effect of L-arginine, which may affect insulin secretion, in patients with diabetes, we use caution in this patient population [1]. There is no “gold standard” therapy for syndrome X, so each patient may respond differently to the initial medical therapy. Thus, we follow these patients closely to monitor their response to treatment.