Abnormal cardiac nerve function in syndrome X.

Abstract

Syndrome X is likely to be caused by a dysfunction of small coronary arteries. Several authors suggested that an increased adrenergic activity could be involved in the pathogenesis of syndrome X, but studies investigating this topic by indirect methods led to conflicting results. We directly investigated cardiac sympathetic nerve function in syndrome X by myocardial radionuclide studies with 123I-metaiodobenzylguanidine (MIBG). Twelve syndrome X patients and 10 healthy controls were enrolled in the study. Cardiac MIBG uptake was assessed calculating the heart/mediastinum (H/M) ratio and a semiquantitative MIBG uptake score. Cardiac MIBG images were normal in all but 1 of controls (10%). Conversely, abnormalities in cardiac MIBG uptake were found in 9 syndrome X patients (75%, p < 0.01). In 5 patients the heart was totally or almost totally invisible on radionuclide MIBG images, while regional defects were found in other 4 patients. The H/M ratio was lower and cardiac MIBG uptake score strikingly higher in syndrome X patients. At 3 hours the H/M ratio was 1.70 +/- 0.6 in patients and 2.19 +/- 0.3 in controls (p = 0.03), while MIBG uptake score was 36.7 +/- 31 and 4.0 +/- 2.5 (p = 0.003) in the 4 groups, respectively. There were no differences between patients and controls in lung and salivary MIBG uptake. Reversible perfusion defects on stress thallium scintigraphy were found in 5 syndrome X patients (45%), all of whom also had abnormal MIBG scintigrams, while all 3 patients with normal MIBG scintigraphy also had normal thallium images. Thus, the function of efferent cardiac adrenergic nerve fibers is strongly impaired in the majority (i.e., 75%) of syndrome X patients. This abnormal function likely contributes significantly to the pathophysiologic and clinical features of syndrome X. We speculate that also the increased perception of cardiac pain reported in these patients could be an expression of the abnormal function of cardiac nerves, reflecting alterations of afferent nociceptive cardiac nerve fibers, as the abnormalities in MIBG uptake reflect alterations of efferent cardiac adrenergic nerve fibers.