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PubMed1994

Results of dobutamine stress echocardiography in patients with syndrome X.

This study describes the results of Dobutamine stress echocardiography in 10 patients with Syndrome X. The diagnosis of Syndrome X was made on the basis of the presence of exertional angina, positive exercise stress test, negative ergonovine stress test and normal coronary arteries at angiography. All patients underwent Dobutamine stress echocardiography after interruption of any antianginal therapy. Dobutamine was infused starting with a dose of 5 mcg/kg/min over 3 minutes with incremental steps of 5 mcg/kg/min every 3 minutes up to a maximal dose of 40 mcg/kg/min. Two-dimensional echocardiography and 12-lead electrocardiography was monitored during the infusion of the drug. Nine patients received the maximal dose while one patient prematurely stopped the test for the occurrence of side effects. None of the ten patients developed segmental left ventricular wall motion abnormalities indicative of myocardial ischemia; ST-segment depression diagnostic for ischemia developed in 30% of patients; angina was elicited in one of these patients and in two additional patients. A hyperkinetic response to Dobutamine infusion involving all the segments of the left ventricle was observed both in patients with and without chest pain or electrocardiographic changes. In patients with Syndrome X Dobutamine induces a hyperkinetic left ventricular response indicative of normal contractile reserve despite the presence in some cases of angina and electrocardiographic signs of ischemia.

Adult↗
PubMed1997

Insulin resistance in cardiac syndrome X and variant angina: influence of physical capacity and circulating lipids.

Insulin resistance has been demonstrated in patients with angina pectoris irrespective of detectable atherosclerosis at coronary angiograms. We compared insulin sensitivity, lipid profiles, and exercise capacity in 20 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls to investigate whether the presentation of the insulin resistance syndrome differs between the two patient groups with disparate vascular abnormalities. All patients had angiographically normal coronary arteries. Maximal oxygen uptake (VO2 max) was determined at bicycle exercise testing. Insulin sensitivity (SI) was assessed by the minimal model analysis of the intravenous glucose tolerance test. Patients with variant angina had significantly lower VO2 max than controls (mean +/- SE, 25.6 +/- 1.5 vs 30.6 +/- 1.4 ml x kg-1 x min-1, p < 0.05), whereas VO2 max in patients with syndrome X was intermediate (27.1 +/- 1.3 ml x kg-1 x min-1). Compared with controls, patients with syndrome X and variant angina had reduced insulin sensitivity (controls, 1.47 +/- 0.16 10(-4) x min-1/per pmol/L vs syndrome X, 0.86 +/- 0.11 10(-4) x min-1 per pmol/L and variant angina, 0.96 +/- 0.15 x 10(-4) x min-1 per pmol/L; analysis of variance, p < 0.05). Only patients with syndrome X exhibited fasting hyperinsulinemia. Patients with syndrome X also had higher fasting concentrations of triglycerides and total cholesterol and lower concentrations of high-density lipoprotein cholesterol than controls. When adjusting SI for variances of VO2 max, differences in SI vanished between controls and patients with variant angina but not between controls and patients with syndrome X. Thus syndrome X and variant angina are both associated with insulin resistance, but lipid abnormalities are only prominent in patients with syndrome X. A variable expression in terms of concomitant disturbances of lipid profiles and disparate influences of physical capacity suggests different underlying mechanisms.

Angina Pectoris, Variant↗
PubMed2000

The brain-heart axis in the perception of cardiac pain: the elusive link between ischaemia and pain.

Angina pectoris is a common symptom and one that can have profound implications for the patient. However, it correlates poorly with the extent of myocardial ischaemia and with prognosis. In order to understand more fully the heterogeneity of the experience of chest pain, we have adopted the technique of functional neuroimaging, where positron emission tomography is used to measure regional cerebral blood flow as an index of regional neuronal activation, during myocardial ischaemia in patients with coronary artery disease. We have been able to delineate those brain areas that are involved in the perception of angina: the hypothalamus, periaquaductal grey, thalami and bilaterally the prefrontal cortex and in the left the inferior anterocaudal cingulate cortex. By studying patients with silent myocardial ischaemia, we have established that the silence is not merely a matter of impaired afferent signalling resulting from autonomic neuropathy, but that it is associated with a failure of transmission of signals from the thalamus to the frontal cortex. At the other end of the spectrum, we have studied patients with syndrome X, a condition of chest pain with ischaemic-like stress electrocardiography (ECG) but entirely normal coronary angiogram; (on the basis of our own and other data we consider an ischaemic aetiology to be most unlikely in this condition). In syndrome X, distinct patterns of cerebral activation were found with characteristic activation of the right anterior insula at its junction with the frontal operculum. In conclusion, we present a unified view of the cerebral handling of afferent signals from the heart throughout this spectrum of experience of chest pain, a view that accounts for the clinical features of the patients studied.

Adrenergic beta-Agonists↗
PubMed1999

Paradoxical increase in coronary flow velocity after termination of acetylcholine infusion is a marker of the impaired vasodilatation at coronary microvessels in patients with angina and normal coronary arteries.

Some patients with anginal chest pain and normal coronary arteries exhibit a paradoxical increase in coronary flow velocity after termination of acetylcholine infusion. The aim of this study was to investigate whether this paradoxical increase in the flow velocity is associated with the impaired microvascular dilatation to pharmacological stimuli. We infused graded doses of endothelium-dependent vasodilator acetylcholine (10, 50, and 100 microg/min for 2 min) and the endothelium-independent vasodilators, papaverine and nitroglycerin, into the left coronary artery in 15 patients with chest pain and normal coronary arteries. Coronary blood flow responses were evaluated by Doppler guidewire and quantitative angiography in the proximal left anterior descending coronary artery. Seven patients showed a paradoxical increase in coronary flow velocity after termination of acetylcholine infusion with the highest dose (100 microg/min), whereas eight showed no change or a decrease in the flow velocity. This was also observed in 50 microg/min of acetylcholine infusion. In patients with a paradoxical increase in the flow velocity, coronary flow velocity responses to acetylcholine during three graded doses were significantly blunted in comparison to those without a paradoxical increase. In contrast, coronary flow reserve to papaverine and nitroglycerin was similar in the two groups. Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups. Papaverine and nitroglycerin also caused a similar degree of coronary dilatation in both groups. These results suggest that the paradoxical increase in coronary flow velocity observed immediately after termination of the intracoronary acetylcholine infusion is a marker of impaired nitric oxide-dependent dilatation of the coronary microvessels in patients with normal coronary arteries. Cathet. Cardiovasc. Intervent. 48:170-177, 1999.

Acetylcholine↗
PubMed1993

Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography: a follow-up study.

A follow-up over a 7-year period demonstrated that 8.6% of all patients subjected to coronary arteriography because of angina pectoris had normal coronary arteries (NCA). The somatic and social prognosis of these patients were evaluated and these were compared to that of an age- and sex-matched group of patients with arteriographically verified coronary atherosclerosis (CAD). On average 44 months after coronary arteriography, 2.4% with NCA had died versus 20.5% with CAD (P < 0.001). Myocardial infarction occurred in 0% (NCA) versus 12.8% (CAD) among survivors (P < 0.001). Coronary revascularization was carried out in 0% (NCA) versus 76.9% (CAD). Chest pain was unchanged or had worsened in 58.2% (NCA) versus 21.1% (CAD) (P < 0.001) and this in the NCA patients was correlated to the occurrence of minimal lesions of the coronary arteries. Of the NCA patients, 33.3% had ischaemia during exercise-ECG. Normalization was seen in 12 patients and newly developed ischaemia in seven patients. Three patients developed ischaemia during hyperventilation test. Eighty percent (NCA) versus 63.9% (CAD) gave up work due to chest pain (P < 0.001). Further, 55.7% (NCA) versus 34.6% (CAD) had reduced daily activities (P < 0.001); similarly, the frequency of divorce was higher in the NCA group (10.2%) than in the CAD group (1.3%) (P < 0.05).

Activities of Daily Living↗
PubMed2001

[Comparison of clinical status and long-term outcome of patients with angina pectoris and normal coronary vessels in coronary angiography or insignificantly narrowed coronary arteries].

UNLABELLED: Among patients investigated with coronary angiography because of effort chest pains, 8-30% are found to have insignificantly narrowed coronary arteries. In this group there are patients with angiographically normal coronary arteries and patients with hemodynamically insignificant atherosclerotic plaques. The aim of this study was to compare clinical status and long-term outcome of patients with effort angina whose epicardial coronary arteries were angiographically normal (Group 1) and patients with luminal diameter stenoses of maximum 30% (Group 2). Between III'91 and IV'97 we identified 230 patients who underwent coronary angiography in the Department of Coronary Artery Disease in Cracow. At the end of the follow-up the patients were asked to complete the self-report questionnaires which evaluated the course of the disease after discharge from the Department and present symptoms. On the basis of the medical records from the hospitalization in the Department and returned questionnaires data of 142 patients (Group 1: 89 patients, 46 men and 43 women, mean age 48.10 +/- 9.2 years; Group 2: 53 patients, 36 men and 17 women, mean age 52.51 +/- 9.6 years) were analyzed. Group 2 patients were older (p = 0.007), with higher prevalence of men (p = 0.05). The mean follow-up was 3.47 +/- 1.7 years for Group 1 and 2.85 +/- 1.7 years for group 2 (p = NS). Left ventricle contractility was normal in both groups. The occurrence of atherosclerosis risk factors was more frequent in Group 2 patients and didn't change significantly over the observation period. There were no deaths or new myocardial infarctions during the observation. Unstable angina occurred in 4 (2.8%) of patients. 33 patients (23.2%) reported hospital treatment for chest pain with mean frequency 0.13 +/- 0.3 hospitalizations/year in Group 1 and 0.09 +/- 0.17 in Group 2 (p = NS). Before coronary angiography this index was significantly higher -0.57 +/- 0.8 hospitalizations/year in group 1 and 0.51 +/- 0.7 in group 2 (p < 0.001 for both groups). Anginal symptoms improved significantly over the observation period. Before coronary angiography majority of patients (60.5% Group 1 patients and 58.3% of Group 2 patients) defined their angina as severe comparing to respectively 7.1% and 2.1% of patients at the end of follow-up (p < 0.05 for both groups). Only 8 (5.6%) of patients remained entirely asymptomatic at the end of the study. During the observation 7 (4.9%) of patients returned to work while 30 (21.1%) of patients retired for medical reasons out of which 25 (17.6%) were due to heart disease. During the follow-up there were no differences between the groups in the professional activity of patients. Group 2 patients were receiving more cardiac medications (mean 2.63 +/- 0.8 vs 2.18 +/- 0.9 at the discharge from the Department; p. = 0.05 and mean 2.52 +/- 0.9 vs 2.02 +/- 1.0 at the end of follow-up; p = 0.04). Group 2 patients were more frequently taking nitrates (86.3% vs 53.7% at the discharge from the Department; p < 0.001 and 77.1% vs 60.9% at the end of the study; p = 0.05) and diuretics. CONCLUSIONS: 1. During follow-up (mean 3.4 years) there were no differences between the groups in the presence of symptoms, frequency of hospitalizations and occurrence of acute coronary events. 2. In both groups severity of anginal symptoms and frequency of hospitalizations decreased significantly. 3. The persistence of cardiac symptoms might have been caused by the presence of atherosclerosis risk factors during the follow-up.

Adult↗
PubMed1995

Recurrent myocardial infarction with angina and normal coronary arteries.

Although it is well recognised that patients with ischemic heart disease can have normal coronary arteries on coronary angiography, most such patients have angina pectoris, whilst a minority have had a previous myocardial infarction. There are few reports of patients with recurrent myocardial infarctions and angina, but with normal coronary arteries on coronary angiography. We describe six patients who had more than one myocardial infarction, confirmed by raised cardiac enzymes and changes on the electrocardiogram. They subsequently developed classical angina and subsequent coronary angiography demonstrated no atherosclerotic coronary artery disease. Coronary artery spasm and diminished coronary reserve may have been contributory factors in these patients.

Adult↗
PubMed1995

Long-term prognosis of patients with anginalike chest pain and normal coronary angiographic findings.

OBJECTIVES: This study analyzes the long-term course of patients with typical angina pectoris or anginalike chest pain and normal coronary angiographic findings. BACKGROUND: In previous studies of such patients the rate of occurrence of typical coronary events during follow-up has differed widely, depending on the duration of the study and the number of patients. METHODS: One hundred seventy-six patients (mean age 48.3 years) who underwent coronary and left ventricular angiography for typical angina or anginalike chest pain were followed up for 5.8 to 15.8 years (median 12.4). By definition, all patients had normal findings on coronary and left ventricular angiograms; exercise test results were positive in 31. RESULTS: Fourteen patients (8%) had a coronary event (0.65%/year) after an average of 9.3 years (median 9.2). Two of the 14 died of a coronary event (0.09%/year), 1 of cardiogenic shock during acute myocardial infarction, 1 suddenly; 4 had a nonfatal myocardial infarction at an average of 8.1 years (median 9.1); 8 had severe angina pectoris after an average of 10.3 years (median 11.1), confirmed by a second angiogram, now with positive findings. Two patients died of a noncoronary cardiac event (chronic cor pulmonale due to obstructive lung disease, acute pulmonary embolism), eight of a noncardiac cause, mainly cancer. None of the 31 patients with a positive exercise test result had a coronary event. Patients with a coronary event had significantly more risk factors (hypercholesterolemia, hypertension, cigarette smoking, diabetes type II) than did those without an event (average 2.4/patient vs. 1.3/patient, p < 0.01). Chest pain persisted in 133 (81%) of the 164 survivors and disappeared in 31 (19%). CONCLUSIONS: Patients with typical angina or anginalike chest pain and normal coronary angiograms have a good long-term prognosis despite persistence of pain for many years; coronary morbidity and mortality are similar to those of the overall population. An increased risk for the development of coronary events is present mainly in patients with elevated risk factors.

Angina Pectoris↗
PubMed2000

New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine.

The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100 microg) and then an ER test (40-64 microg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8+/-0.8) was significantly lower than that of patients in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.

Acetylcholine↗
PubMed1994

Analysis methods to improve the diagnostic power of treadmill exercise stress testing in patients with suspected angina pectoris.

To assess the ability of 3 established analysis methods in exercise stress electrocardiography to non-invasively detect the presence of coronary artery disease (CAD), 67 consecutive patients who had typical angina, positive exercise stress electrocardiography (ST segment depression > or = 1 mm) and coronary arteriography were studied. Thirty-three patients had significant CAD, and 34 had normal coronary arteriograms. The results showed that the Treadmill Score Method, utilising both ST and non-ST segment variables, had the highest accuracy in predicting disease. The predictive power of all 3 methods was lower in females.

Adult↗
PubMed2005

Effect of spinal cord stimulation on spontaneous and stress-induced angina and 'ischemia-like' ST-segment depression in patients with cardiac syndrome X.

AIMS: A significant number of patients with cardiac syndrome X (CSX) present frequent episodes of severe chest pain, refractory to maximal multi-drug therapy. A few, small, uncontrolled data suggested that spinal cord stimulation (SCS) may have favourable clinical benefits in these patients. METHODS AND RESULTS: We studied 10 CSX patients who were being treated by SCS for refractory angina pectoris for 17+/-16 months (median 8). Patients were randomized to either continue or withdraw SCS for a period of 3 weeks and were then crossed over to the other condition for a further 3-week period. During each 3-week period patients kept a detailed diary of angina episodes occurring in the last 2 weeks of each phase. Furthermore, at the end of each 3-week period, angina status was also assessed by Seattle Angina Questionnaire (SAQ), a 0-100 visual analogue scale (VAS), and patients underwent 24-h Holter monitoring (HM) and echocardiographic dobutamine stress test (DST). Compared with the withdrawal phase, SCS reduced the number (P=0.01), duration (P=0.022), and severity (P=0.011) of angina episodes, and nitrate consumption (P=0.042). SAQ scores (P< or =0.013 for all) and VAS (P<0.001) were also improved, the number of episodes of ST-segment depression on HM was decreased (P=0.014), and time to angina (P=0.045) and to 1 mm ST-segment depression (P=0.04) during DST were both prolonged by SCS. CONCLUSIONS: Our data point out that SCS may be an effective form of treatment in patients with CSX suffering from frequent angina episodes significantly impairing quality of life (QOL) and refractory to maximally tolerated drug therapy.

Aged↗
PubMed2001

Slow coronary flow: a distinct angiographic subgroup in syndrome X.

Patients evaluated for chest pain with angiographically normal coronary arteries are usually labelled syndrome X. A portion of these patients may not have a cardiac cause for their symptoms. The authors aimed to study a subset within this group who showed the phenomenon of slow coronary flow (SCF) as evidenced by a slow antegrade progression of the dye on the coronary arteriogram to see if this could be used as a marker of myocardial ischemia. This observational study included 207 patients being evaluated for suspected coronary artery disease and found to have normal coronary angiograms. SCF was seen in 49 of these patients (23.7%) while the remaining 158 (76.3%) had normal coronary flow (NCF), as detected by the corrected thrombosis in myocardial infarction (TIMI) frame count method (TIMI frame count more than 2 SD of normal). Forty of the 49 patients (82%) in the SCF group had classical angina as compared with only 51 of the 158 patients (32%) in the NCF group (p<0.01). Also, a definitively positive exercise test was observed more commonly in the SCF group than in the NCF group (71% vs 42%, p < 0.01). The authors conclude that SCF patients constitute a definite subset within the wide spectrum of syndrome X and that the phenomenon of SCF could be used as a marker for myocardial ischemia.

Adult↗
PubMed1999

[Analysis of referral diagnoses of patients with normal coronary angiogram].

BACKGROUND AND AIMS: Angiography permits an evaluation of the morphology of the coronary artery, stratification of risk and optimal therapeutic management in patients with suspected coronary artery disease (CAD). The sophisticated apparatus, cost and invasiveness of the procedure necessitate well-considered application of this method. In spite of an exact documentation of the patient's medical history and careful establishment of the indication, the results of angiography are often normal. Therefore, it appears important to analyse the referral diagnoses in patients with normal coronary angiograms. PATIENTS AND METHODS: We studied 1000 consecutive patients (625 men, 375 women, mean age 63.1 years) who underwent coronary angiography at our institution from January to May 1998. All patients were included in the retrospective analysis of the referral diagnoses. RESULTS: 875 patients (554 men, 321 women) were referred due to suspected CAD; 173 of these had normal angiographic findings (20%; 73 men, 100 women; mean age 58.4 years). The referral diagnoses were as follows: unstable angina in 62 patients (36%), stable angina in 40 patients (23%), chest pain and pathological findings of non-invasive testing in 32 patients (19%), atypical chest pain in 25 patients (14%), previous myocardial infarction and multiple risk factors in 7 patients each (4% each). Gender-related differences were remarkable. Only 73 of the 554 referred men (13%) had normal angiographic findings, whereas in women the rate of normal results was more than twofold higher, i.e. 100 of the 321 referred women (31%) had normal angiographic findings (p < 0.01). CONCLUSIONS: Among 875 patients referred to our catheter laboratory for coronary angiography due to suspected CAD, normal angiographic results were documented in 20%. The high frequency of the referral diagnosis 'unstable angina' and 'pathological result of noninvasive testing' was as remarkable as the high proportion of women among patients with normal findings.

Adult↗
PubMed1997

Insulin-like growth factor-I, insulin, and angina pectoris secondary to coronary atherosclerosis, vasospasm, and syndrome X.

We measured growth hormone-related substances in patients with angina pectoris precipitated by different underlying disorders. Although hyperinsulinemia was more pronounced in patients with angina pectoris secondary to atherosclerotic coronary disease than in patients with syndrome X and variant angina, we found no evidence that growth hormone-related substances including insulin-like growth factor-I are associated with coronary atherosclerosis.

Angina Pectoris↗
PubMed2005

Anginalike pain and normal coronary arteries. Uncovering cardiac syndromes that mimic CAD.

Atherosclerotic CAD is the most common cause of cardiac chest pain in Western countries. Other cardiac syndromes may also cause anginalike pain and may be difficult to differentiate from atherosclerotic CAD. It is essential to make this distinction, because management and prognosis of these conditions are entirely different. A detailed history and, in some cases, special diagnostic methods can help make the diagnosis. When evaluating patients with anginalike chest pain and normal coronary arteries, physicians need to consider this group of diseases and tailor workup and diagnosis on an individual basis.

Adrenal Gland Neoplasms↗
PubMed1998

Syndrome X and endothelial dysfunction.

OBJECTIVE: Syndrome X (angina, normal coronary arteriogram and positive exercise test) remains an enigma with unexplained features and apparent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dysfunction, (ii) myocardial thallium201 defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its consequences can be improved by oral L-arginine. METHODS: Flow-mediated brachial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium201 defects and no known cause of endothelial dysfunction, and a normal control group. Syndrome X patients entered a 4-week randomised double-blind placebo-controlled cross-over trial of oral L-arginine (7 g twice daily), with brachial artery studies, exercise tests and technetium99 tetrafosmin scans. RESULTS: Flow-mediated dilatation was absent in Syndrome X vs. normal. Stress technetium99 tetrafosmin and thallium201 scans showed similar defects. Flow-mediated dilatation, symptom-limited exercise duration and peak oxygen consumption (VO2max) were increased but rate-pressure-product (RPP) and radionuclide defects were unchanged after L-arginine vs. placebo. CONCLUSIONS: The study supports coronary microvascular rather than myocardial dysfunction and shows loss of flow-mediated dilatation in systemic arteries. Oral L-arginine improved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endothelial dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvascular distribution.

Administration, Oral↗