Pathophysiology and Natural History Left Ventricular Performance

Thirty-three patients with chest pain despite angiographically normal coronary arteries underwent both coronary flow studies during pacing and resting and exercise gated blood pool scintigraphy. During atrial pacing after administration of ergonovine, those patients developing their typical chest pain demonstrated significantly lower great cardiac vein flow (97 ± 31 vs 150 + 33 ml/ min, p < .001), higher coronary resistance (1.27 -+0.43 vs 0.77 ± 0.18 mm Hg/ml/min, p < .005), and less lactate consumption (30.5 ± 22.0 vs 69.7 + 41.1 mM * ml/min, p < .005) and a higher left ventricular end-diastolic pressure after pacing (20 + 4 vs 12 ± 1, p < .001) compared with those without pain and in the absence of significant luminal narrowing of the epicardial coronary arteries. The 26 patients with abnormal vasodilator reserve demonstrated reduced left ventricular ejection fraction during exercise (58 ± 8%) compared with the seveni patients with appropriate vasodilator reserve (66 ± 4%, p < .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 ± 10%, p < .001). In addition, 12 of the 26 patients with abnormal vasodilator reserve demonstrated exercise-induced regional wall motion abnormalities. Many of these patients also manifested impaired left ventricular diastolic filling at rest compared with the control subjects (peak filling rate 2.6 + 0.7 vs 3.2 -+ 0.7 end-diastolic volume/sec, p < .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia. Circulation 71, No. 2, 218-226, 1985. MUCH DEBATE has focused on whether or not patients with chest pain despite normal epicardial coronary arteries truly experience myocardial ischemia. I6 Several investigators have found that many of these patients clearly have a noncardiac cause of their pain, including esophageal,7 8 chest wall,9 and psychosomatic causes.'0 However, others have found many such patients to have abnormal exercise electrocardiograms, 11-18, 23 abnormal lactate metabolism during infusion of isoproterenol or atrial pacing,'l 14, 17. 191, 23 elevation of left ventricular end-diastolic pressure during exercise,'2 14 22 and limited vasodilator reserve after infusion of dipyridamole.23 More recently, radionuclide studies have demonstrated abnormal myocardial perfusion'118 24-26 and abnormal left ventricular function From the Cardiovascular Diagnosis and Nuclear Cardiology Sections, Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda. Address for correspondence: Richard 0. Cannon III, M.D.. Building 10, Room 7B-15, National Institutes of Health, Bethesda, MD 20205. Received May 22, 1984; revision accepted Oct. 25, 1984. in patients with chest pain and angiographically normal coronary arteries.'8 27. 28 Results of such studies have been interpreted as "false positives" at one extreme and as indicative of myocardial ischemia of uncertain cause at the other. The most compelling argument against the presence of myocardial ischemia is that the prognosis of patients with chest pain and angiographically normal epicardial coronary arteries is believed to be benign,'0 13-15 29-31 even if they continue to experience frequent and disabling chest pain.30 31 We recently found that many patients with chest pain who have angiographically normal coronary arteries and no evidence of large vessel spasm after ergonovine challenge demonstrate a limited capacity to decrease coronary resistance and increase coronary flow in response to atrial pacing.32 This apparent inappropriate vasodilator reserve was associated with the patient's typical chest pain and diminished lactate consumption. Cold pressor testing and ergonovine infusion resulted in unmasking this abnormality in many CIRCULATION 218 by gest on A ril 6, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-LEFT VENTRICULAR PERFORMANCE patients with apparently normal flow responses to pacing alone, and in exacerbating abnormal vasodilator reserve in others. No significant change in epicardial coronary artery luminal diameter was noted after cold pressor testing or ergonovine, suggesting that this abnormality was localized in vessels too small to be imaged angiographically: either small coronary arteries or arterioles. However, the question remains whether this abnormality of coronary vasodilator reserve truly results in myocardial ischemia. In the current study, we compared left ventricular function at rest and during exercise in patients with chest pain related to impaired coronary vasodilator reserve with that in subjects of similar age and sex distribution and free of known heart disease.