Normal Epicardial Coronary Arteries Research Articles

Improved exercise capacity with acute aminophylline administration in patients with syndrome X

The efficacy of the adenosine receptor blocker aminophylline on exercise capacity in patients with effort ischemia and documented coronary artery, disease has been previously documented. In this study the effect of aminophylline on effort electrocardiographic (ECG) alterations and chest pain was tested in eight patients with syndrome X (anginal chest pain on effort, ischemic ECG changes during exercise, positive dipyridamole test, normal epicardial coronary arteries on angiography and absence of coronary spasm after ergonovine).After double-blind, randomized intravenous infusion of aminophylline (6 mg/kg body weight over 15 min) or placebo (20 ml of saline solution over 15 min), the eight patients with syndrome X underwent an upright bicycle exercise stress test on 2 consecutive days. After aminophylline, there was an increase in effort tolerance (aminophylline 7.7 ± 1.2 min of exercise versus placebo 5.6 ± 0.9, p < 0.01) paralleled by an increase of the rate-pressure product (mm Hg × beats/min x 1/100) at 0.1 mV of ST segment depression or at peak exercise (aminophylline 278 ± 55 versus placebo 230 ± 24, p < 0.05). Aminophylline provoked the abolition of ECG signs of ischemia in all eight patients.Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced chest pain and ischemia-like ECG changes in syndrome X. This effect occurs possibly through the prevention of myocardial flow maldistribution elicited by inappropriate adenosine release during effort in the presence of increased coronary resistance at the level of small intramural coronary arteries. This study, however, does not document the ischemic nature of effort-induced pain and ECG alterations in syndrome X.

Myocardial ischemia without atherosclerosis.

Myocardial ischemia in the presence of normal epicardial coronary arteries can be caused by an abnormality in the microcirculation or myocardial cell or by hypertrophy resulting in depressed coronary vasodilator reserve. Newly developed methods of assessing coronary blood flow and velocity make definitive diagnosis possible. Treatment, which may be difficult, includes therapy for the underlying cause, a calcium blocker, and nitrates.

Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy

Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease ≤5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 ± 15 vs 75 ± 11%, respectively, p < 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 ± 7 vs 21 ± 6 mm, p < 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p < 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p < 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p < 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.

Effect of surgical reduction of left ventricular outflow obstruction on hemodynamics, coronary flow, and myocardial metabolism in hypertrophic cardiomyopathy.

To assess the impact of operative reduction of left ventricular outflow obstruction in hypertrophic cardiomyopathy, measurements of great cardiac vein flow, oxygen and lactate content, left ventricular pressures, and cardiac index were measured at rest and during pacing stress in 20 consecutive patients (13, myotomy-myectomy; six, mitral valve replacement; one, both myotomy-myectomy and mitral valve replacement) who underwent both preoperative and postoperative studies. All had angiographically normal epicardial coronary arteries. Operation resulted in reduction in outflow gradient (64 +/- 38 to 4 +/- 7 mm Hg, p less than 0.001) and in left ventricular systolic pressure (186 +/- 32 to 128 +/- 22 mm Hg, p less than 0.001) and was associated with reduction in great cardiac vein flow (101 +/- 26 to 78 +/- 16 ml/min, p less than 0.001) and oxygen consumption in the anterior left ventricle and septum (11.9 +/- 4.1 to 8.4 +/- 1.9 ml O2/min, p less than 0.001) in the basal state. During rapid atrial pacing, 13 of 20 patients experienced chest pain postoperatively, whereas all 20 developed chest pain during preoperative pacing, with an improvement in pacing anginal threshold (or heart rate 150 if no chest pain was experienced) of 16 +/- 18 beats/min (p less than 0.001). The peak great cardiac vein flow (161 +/- 41 to 131 +/- 45 ml/min, p less than 0.025) and myocardial oxygen consumption (19.4 +/- 6.1 to 14.3 +/- 5.5 ml O2/min, p less than 0.005) during pacing, which correlated directly with the severity of the basal left ventricular gradient (p = 0.011 and p = 0.002, respectively), were also reduced by surgery. Lactate metabolism during pacing changed from net production before surgery to net consumption after operation (-17 +/- 47.6 to 4.4 +/- 29.8 mumol/min, p less than 0.01), with six of 20 patients producing lactate after surgery compared with 13 of 20 before surgery (p = 0.06). The six patients with the highest peak great cardiac vein flow (greater than 175 ml/min) during preoperative pacing had greater symptom and metabolic benefit during pacing after surgery compared with the 14 patients with lower peak coronary flow. Postpacing left ventricular end-diastolic pressure (30 +/- 7 to 23 +/- 7 mm Hg, p less than 0.001) and pulmonary artery wedge pressure (24 +/- 6 to 20 +/- 5, p less than 0.001) were reduced after surgery.(ABSTRACT TRUNCATED AT 400 WORDS)

Dipyridamole-echocardiography test in essential hypertensives with chest pain and angiographically normal coronary arteries.

Microvascular angina--chest pain syndrome in the presence of angiographically normal epicardial coronary arteries and reduced flow reserve--has been described in patients with essential hypertension (EH) and linked to the development of left ventricular hypertrophy (LVH). We performed a dipyridamole-echocardiography test (DET: 2D-echo and 12 lead ECG monitoring with dipyridamole infusion, up to 0.84 mg/kg over ten minutes) in 28 essential hypertensives meeting the following inclusion criteria: (1) history of chest pain; (2) angiographically normal coronary arteries; (3) normal resting regional and global left ventricular function. A group of 12 (age- and sex-matched) normotensives with the same inclusion criteria, as well as with negative exercise stress test, was also evaluated. During DET, none of the essential hypertensives or the control group developed a regional dyssynergy of contraction. Fifteen essential hypertensives and two in the control group had a diagnostic (greater than 0.1 mV from baseline) ST segment depression on ECG tracing (54 v 17%, P less than .01); 16 essential hypertensives and two in the control group had chest pain (57 v 17%, P less than .01). None of the control group and nine of the essential hypertensives had echocardiographically assessed LVH. In the essential hypertensive group ventricular hypertrophy was present in seven of 20 patients with and in two of eight patients without dipyridamole induced chest pain and/or ST segment depression (35% v 25%, P = NS). In conclusion, essential hypertensive patients with chest pain and angiographically normal coronary arteries frequently show echocardiographically silent angina and/or ST segment depression during DET.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intracoronary injection of acetylcholine on coronary arterial hemodynamics and diameter

To examine the effects of intracoronary injection of acetylcholine on coronary blood flow and on coronary arterial diameter in humans, acetylcholine was injected into the left coronary artery in 32 adult patients (21 men and 11 women with a mean age of 54 years, range 37 to 65) with normal or almost normal coronary arteriographic findings. Patients with angina pectoris, myocardial infarction and severe cardiac diseases were excluded. Temporary right ventricular pacing was set at a rate of 60 beats/min to prevent transient bradyarrhythmias during intracoronary injection of acetylcholine. Measurements of coronary sinus blood flow and coronary vascular resistance and quantification of coronary arterial diameters using a computer-assisted technique were performed before and after each injection of 20, 50 and 100 μg of acetylcholine. Significant increase in coronary sinus blood flow and significant decrease in coronary vascular resistance occurred after intracoronary injection of acetylcholine. In contrast, mean diameter of normal epicardial coronary artery tended to decrease and that of irregular epicardial coronary artery decreased significantly after intracoronary injection of acetylcholine. Intracoronary injection of acetylcholine increases coronary blood flow, suggesting vasodilation in the coronary arteriolar bed, while it induces vasoconstriction in most of epicardial coronary arteries in adult humans.

R wave amplitude changes during stress testing in ischemic patients with normal epicardial coronary arteries

R wave amplitude changes during stress testing were validated in 12 ischemic patients with normal coronary angiograms. The data were compared with findings obtained from 10 patients with clinical and angiographic evidence of coronary arterial disease and 10 normal controls. An abnormal R wave amplitude response occurred in 83.3% of the group with normal coronary angiography, in 80% of the group of patients with clinical and angiographic evidence of coronary arterial disease, and in only 10% of the control group. The similarity of R wave amplitude changes in the first two group suggests that these changes are related to ischemia. If so, then R wave amplitude response to exercise could be of value in the electrocardiographic diagnosis of ischemia in patients with angiographically normal coronary arteries.

Limited coronary flow reserve after dipyridamole in patients with ergonovine-induced coronary vasoconstriction.

Patients with anginal chest pain despite angiographically normal coronary arteries and left ventricles may have abnormalities of coronary flow reserve. Twenty-five patients were found to have limited flow reserve during rapid atrial pacing after administration of 0.15 to 0.30 mg iv ergonovine, associated with precipitation of chest pain and hemodynamic and metabolic evidence of myocardial ischemia. No significant narrowing occurred in epicardial coronary artery luminal diameter. An additional 15 patients had no chest pain during pacing; because they developed significantly higher great cardiac vein flow and lower coronary resistance they were considered to have normal vasodilator reserve. After administration of dipyridamole (0.5 to 0.75 mg/kg iv), the lowest absolute levels to which coronary resistance fell (0.79 +/- 0.23 vs 0.47 +/- 0.12 mm Hg X min/ml; p less than .001) and the maximal absolute levels to which great cardiac vein flow rose (134 +/- 34 vs 202 +/- 45 ml/min; p less than .001) were impaired in the 25 patients with ergonovine-induced flow limitation compared with the 15 patients without flow limitation after ergonovine. In addition, 18 of the 25 patients with limited flow reserve after dipyridamole experienced chest pain despite an increase in coronary flow. In these patients, dipyridamole-induced increased flow across small prearteriolar coronary arteries, which were narrowed because of abnormal tonus or sensitivity to vasoconstrictor stimuli, could have resulted in a transmural redistribution of blood flow away from the subendocardium, precipitating subendocardial ischemia. These studies suggest that patients with anginal chest pain despite normal epicardial coronary arteries may have exaggerated coronary responses to vasoconstrictor stimuli, which can result in myocardial ischemia during stress, as well as attenuated responses to coronary vasodilator stimuli.

Response of normal and diseased epicardial coronary arteries to vasoactive drugs: quantitative arteriographic studies

Coronary vasodilators known to be effective in effort and vasospastic angina were studied in 93 patients undergoing catheterization for evaluation of chest pain. The ischemia-provoking stresses were isometric handgrip (25% of maximum for 4 to 5 minutes) or ergonovine maleate (0.2 mg intravenously). Hemodynamic changes and changes in angiographic diameter of epicardial coronary arteries were measured during these stresses, with and without drug administration. Drugs included intravenous diltiazem (0.25 mg/kg load + 0.003 mg/ kg/min), intravenous verapamil (0.14 mg/kg load + 0.0075 mg/kg/min) and intracoronary (0.012 mg/min X 4 minutes) and sublingual (0.4 mg) nitroglycerin. From these studies, the following statistically valid conclusions were reached. First, nitroglycerin is a potent dilator of epicardial coronary arteries, increasing normal luminal area an average of 28% and luminal area in significantly stenotic segments by 29%. Second, verapamil and diltiazem are nonsignificant epicardial coronary dilators (9% and 4% luminal area increase, respectively). Similarly, diltiazem does not dilate significant coronary stenoses. Third, sustained isometric handgrip increases systemic blood pressure and heart rate by reflex activation of the sympathetic nervous system. By this means, handgrip also constricts luminal area in normal and diseased coronary segments by 20% and 22%, respectively. One result of these changes is a handgrip-induced, ischemic 56% rise in pulmonary wedge pressure in patients with significant stenosis. Fourth, intracoronary nitroglycerin, in very small doses, does not block the systemic hemodynamic response to handgrip, but prevents handgrip-induced coronary constriction and the associated ischemic left ventricular dysfunction. Thus, in states of sympathetic activation, vasotonic constriction of significant lesions is a major mechanism of the ischemic response, and its prevention is a major mechanism of the nitroglycerin response. Last, verapamil and diltiazem infusions block the coronary constriction observed during handgrip in normal and diseased coronary segments. Verapamil almost completely abolishes the coronary constriction seen after ergonovine. Thus, unlike nitroglycerin, verapamil and diltiazem are not direct epicardial coronary dilators, but act by preventing the constriction of diseased coronary segments induced by α-adrenergic and serotonergic coronary receptor stimulation.

Decreased coronary reserve in primary scleroderma myocardial disease.

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.

Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve.

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 less than .001), higher coronary resistance (1.27 +/- 0.43 vs 0.77 +/- 0.18 mm Hg/ml/min, p less than .005), and less lactate consumption (30.5 +/- 22.0 vs 69.7 +/- 41.1 mM . ml/min, p less than .005) and a higher left ventricular end-diastolic pressure after pacing (20 +/- 4 vs 12 +/- 1, p less than .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 seven patients with appropriate vasodilator reserve (66 +/- 4%, p less than .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 +/- 10%, p less than .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 less than .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia.

Chest pain and “normal” coronary arteries—Role of small coronary arteries

To study the mechanism of chest pain in patients with insignificant epicardial coronary artery disease, 50 patients underwent great cardiac vein (GCV) flow, oxygen content and lactate determinations at rest and during pacing, and left ventricular end-diastolic pressure (LVEDP) measurements at rest and after pacing. Twenty-four patients having typical chest discomfort during pacing demonstrated significantly lower increase in flow from baseline (36 ± 18% versus 86 ± 24%, p < 0.001) and decrease in coronary resistance (−17 ± 12% versus −43 ±7%, p < 0.001) compared with 26 patients without pacing-induced chest pain, despite no significant difference in myocardial oxygen consumption (MVO 2) between the 2 groups. Lactate consumption at a heart rate (HR) of 150 beats/min was significantly less (28.3 ± 21.5 versus 51.3 ± 35.8 mM· ml/min, p < 0.001) and the increase in LVEDP from rest to after pacing was significantly greater (5 ±2 versus 1 ± 2 mm Hg, p < 0.001) in the chest pain group. After administration of ergonovine, 0.15 mg intravenously, to 46 of these patients, 31 had typical pain either at rest (1 patient) or during pacing. This group had significantly lower increase in flow (38 ± 20% versus 107 ± 38%, p < 0.001), and decrease in coronary resistance (-16 ± 12% versus −45 ± 11%, p < 0.001) compared with the 15 patients not having chest pain, despite no significant difference in MVO 2 between the 2 groups. Patients with chest pain also had lower lactate consumption at a HR of 150 beats/min (39.2 ± 23.6 versus 65.3 ± 46.3 mM·ml/min, p < 0.01), greater arterial-GCV oxygen difference (12.5 ± 1.3 versus 11.6 ± 1.0 ml O 2/100 ml, p < 0.05), and a more marked increase in LVEDP from rest to after pacing (11 ± 3 versus 5 ± 2 mm Hg, p < 0.001). Quantitative coronary arteriography demonstrated no significant luminal narrowing of the epicardial coronary arteries in response to ergonovine. These data are consistent with the hypothesis that some patients with chest pain and angiographically normal epicardial coronary arteries have dynamic abnormalities of the small coronary arteries or coronary microcirculation that cause abnormal vasodilator reserve or vaso-constriction, resulting in myocardial ischemia and angina pectoris.

Cardiac syndrome X – a challenge for Cardiologist

Cardiac syndrome X is a multifactorial disorder. A triad of angina pectoris, positive exercise tolerance test (ETT) and angiographically normal epicardial coronary arteries, is called Cardiac syndrome X. Though the normal epicardial coronary arteries, patients present with debilitating chest pain which increases morbidity and poor quality of life. The particular cause of Cardiac syndrome X is still unknown. Many large trails are on going to detect exact pathogenesis of this condition. A multiple treatment regimens may reduce the morbidity and improve the quality of life of these patients. Key words: Angina pectoris; exercise tolerance test. DOI: 10.3329/uhj.v6i1.7188University Heart Journal Vol.6(1) 2010 pp.32-34

Chest Pain and Exercise Induced Ischemia with Angiographically Insignificant Coronary Arterial Disease: Clinical Presentation and Follow-Up

Angiography of patients with typical chest pain reveals normal epicardial coronary arteries in about 15-20%. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in this subset of the patients. Total 58 patients (42 females) with mean age 42±7 years who were undergoing coronary angiogram in the Department of Cardiology, University Cardiac Center, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2005 to December 2009 were evaluated. The patients were recruited on the basis of presence of history of chest pain, with normal resting ECG and ischemia like ECG changes during exercise stress test. 32.8% patients had hypertension and 15.5% were diabetics, 19.0% had dyslipidemia and 6.9% had family history of ischemic heart disease. All the patients were having positive exercise stress test. Angiographic findings showed luminal irregularities in 29.3% patients, 15.5% patients had luminal stenosis less than 30% and rest had normal coronary angiogram. Follow up of the patients after one and six months of angiogram was done. After one month 63.8% patients remained symptomatic and after six months 63.3% patients remained symptomatic despite maximum medical management. The pathophysiology and appropriate management of this subset of the patients still remained a challenge for physicians. Optimum management of cardiovascular risk factors is very important issue in this group of patients.Key words: Angiography; Epicardial coronary arteries; Exercise stress test; Cardiovascular risk factors. DOI: 10.3329/uhj.v6i1.7187University Heart Journal Vol.6(1) 2010 pp.27-31