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PubMed1999

Recurrent syncopal episodes of neurocardiogenic origin in a patient suffering from cardiac syndrome-X.

We describe the case of a 44-year-old man, with a history of recurrent syncopal episodes and effort angina, the latter attributed to cardiac syndrome-X, who was admitted to our department because of a syncopal episode. During his hospitalization laboratory investigations including haematologic and blood chemical findings, head C/T scan, electroencephalogram, 48-hour Holter monitoring, electrophysiologic testing and echocardiographic study disclosed no abnormalities. On the contrary, a passive upright tilt testing was found to be positive, resulting, approximately, in a 10-seconds time interval of asystole accompanied by syncope. The association in the same patient of cardiac syndrome-X and neurocardiogenic syncope, although never described before, might be explained by a similar pathophysiological mechanism, which is a sympathovagal imbalance.

Adult↗

PubMed1997

Impaired left ventricular filling dynamics in patients with angina and angiographically normal coronary arteries: effect of beta adrenergic blockade.

OBJECTIVE: To assess exercise performance and resting left ventricular filling dynamics in patients with syndrome X (SX) in basal conditions and after 10 days treatment with oral atenolol. DESIGN AND PATIENTS: Exercise performance was studied and left ventricular filling assessed by Doppler-derived transmitral flow pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with angina, a positive exercise test, and angiographically smooth coronary arteries. Patients were studied after two 10 day treatment periods with either atenolol or placebo in a single-blind, randomised, crossover trial. The same protocol was followed in 10 patients with documented coronary artery disease (CAD) and in 13 controls (C). RESULTS: Unlike the controls, patients with SX and those with CAD consistently showed exercise-induced ST segment abnormalities and impaired resting left ventricular filling while on placebo. Atenolol significantly reduced episodes of angina, completely prevented exercise-induced ST segment changes in 18 SX patients, and delayed their onset in all patients with CAD: in both groups the agent significantly improved Doppler-derived indices (mean (SD)) of ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37), respectively). CONCLUSIONS: The objective documentation of left ventricular filling abnormalities may be useful in confirming the clinical diagnosis of SX and in providing objective evidence of therapeutic benefit. The similarity of the symptoms and electrocardiographic and ventricular filling abnormalities found in patients with SX and in those with CAD suggests that ischaemia is involved in both groups.

Adrenergic beta-Antagonists↗

PubMed1994

[Does syndrome X exist?].

The syndrome X is an entity characterised by the association of chest pain on exercise and a positive exercise stress test in patients with normal coronary angiography. However, this diagnosis can only be admitted when all other causes of angina with normal coronary arteries have been excluded. They include angina secondary to coronary artery spasm and myocardial hypertrophy. A review of the literature based on 26 publications recensing 822 patients shows that these criteria are not always respected: a really positive exercise stress test is an inclusion criterion in only 13 studies and concerns only 313 patients (38.1%); myocardial hypertrophy and coronary spasm were formally excluded in only 278 (33.3%) and 228 patients (27.7%) respectively. Taking into consideration only the patients of these 26 series with a positive exercise stress test after exclusion of coronary spasm and myocardial hypertrophy, 143 (17.4%) may be considered to be due to syndrome X. Syndrome X is a real entity but its incidence is usually overestimated. It is appropriate to distinguish it from other conditions associating, though the exercise stress test is negative, chest pain on effort and the positivity of a test considered to be indicative of myocardial ischaemia.

Exercise Test↗

PubMed1998

Remnant-like particle cholesterol is a major risk factor for myocardial infarction in vasospastic angina with nearly normal coronary artery.

We investigated the association of remnant-like particle cholesterol (RLP-C), with vasospastic angina (VSA). We selected 66 subjects with nearly normal coronary artery as a control group, and 74 VSA with nearly normal coronary artery, of whom 19 had prior myocardial infarction (MI). Coronary risk factors, triglyceride, lipoproteins and apolipoproteins were evaluated using stepwise discriminant analysis, smoking was the only discriminator of the control group from VSA and RLP-C was the only discriminator of VSA with MI from VSA without MI. In comparison between VSA with and without MI, using stepwise logistic regression analysis, the only significant variable was RLP-C, and odds ratio of RLP-C for MI was 1.59. Thus, RLP-C is a major discriminator of VSA with MI and appears to be a major risk factor for MI in VSA.

Adult↗

PubMedDate not supplied

Profile of coronary risk factors in patients with manifest ischaemia and normal coronary arteries.

Risk factor profile of 142 patients with normal epicardial coronary arteries (86 males, 56 females, mean age 47 +/- 11 years) out of 1,508 consecutive patients undergoing coronary angiography was analysed. The mode of presentation in these patients was old or recent myocardial infarction (16.1%), unstable angina (12.0%), angina on effort (43.7%), atypical chest pain (8.5%), and anginal equivalent (19.7%). One or more stress test was positive in the majority (88%) of patients. Though the majority (39.5%) of patients had one risk factor, multiple (two or more) risk factors were not uncommon. Risk factor profile in patients with normal coronaries included hypertension (45.7%), dyslipidemia (33.8%), obesity (19.7%), positive family history of coronary artery disease (18.3%), cigarette smoking (16.1%), and minor risk factors (hyperuricemia, sedentary life style, Type A personality, oral contraceptive intake -15.4%). The mechanism of myocardial ischemia in patients with normal coronary arteries is not fully understood. We conclude that approximately one tenth of patients with clinically manifest coronary artery disease and one or more conventional risk factors do not have atherosclerotic changes in their epicardial coronary arteries as seen on coronary angiography.

Coronary Angiography↗

PubMed1994

[Syndrome X. Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography].

Over a seven year period, 8.6% of 990 patients subjected to coronary arteriography because of angina pectoris were found to have normal coronary arteries (NCA). The subsequent histories of these patients were compared to those of a group of patients (N = 112) with coronary atherosclerosis (CAD). On average 44 months after coronary arteriography, 2.4% (NCA) had died versus 20.5% (CAD) (p < 0.001). Myocardial infarction had occurred in 0% (NCA) versus 12.8% (CAD) of the survivors (p < 0.001). Chest pain was unchanged or had worsened in 58.2% (NCA) versus 21.1% (CAD) (p < 0.001). Of the NCA patients, 33.3% had ischaemia during exercise-ECG. Three patients developed ischaemia during hyperventilation test. Eighty % (NCA) versus 63.9% (CAD) gave up work due to chest pain (p < 0.05). Further, 55.7% (NCA) versus 34.6% (CAD) had reduced daily activities (p < 0.01); similarly, the frequency of divorce was higher in the NCA group (10.2%) than in the CAD group (1.3%) (p < 0.05).

Adult↗

PubMed1997

Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X).

BACKGROUND: Patients with syndrome X (exertional angina, positive exercise test, normal coronary arteriogram) have an altered perception of cardiac pain. This symptom may arise from increased sensitivity to adenosine. Previous studies suggest that intravenous aminophylline (an adenosine receptor blocker) improves exercise tolerance in patients with this disorder. OBJECTIVE: To examine the efficacy of oral aminophylline in syndrome X. METHODS: 13 patients (11 women and two men, mean (SD) 54 (6) years) with syndrome X were studied. Patients were randomised in a double blind crossover study to receive either oral aminophylline or placebo for three weeks. All patients underwent symptom limited exercise testing and ambulatory electrocardiography at the end of each three week period. RESULTS: 10 patients completed the study. The time to angina during exercise testing in patients who were given aminophylline was longer than for the placebo group (mean (SD) 632 (202) seconds v 522 (264) seconds, P = 0.004). Peak exercise ST depression did not differ significantly between patients who received aminophylline and those administered placebo (mean (SD) -1.9 (0.7) mm v -1.5 (0.8) mm). Six patients taking aminophylline reported a reduction in the total number of episodes of chest pain during the three weeks, but the frequency and duration of ST segment depression during Holter monitoring was unchanged. CONCLUSION: Oral aminophylline has a favourable effect on exercise induced chest pain threshold in patients with syndrome X. The disparate effects on symptoms and ST segment changes are intriguing and further study is warranted.

Administration, Oral↗

PubMed2005

Cardiac syndrome X.

Cardiac syndrome X, the triad of angina pectoris, a positive exercise electrocardiogram for myocardial ischaemia and angiographically smooth coronary arteries, is frequently associated with debilitating symptomology, increased psychological morbidity and a poor quality of life. While various avenues of research have been undertaken, there are as yet no definitive conclusions regarding the exact pathogenesis of the condition. A number of physiological mechanisms have been explored, including the existence of underlying myocardial ischaemia, suggested endothelial dysfunction, abnormal pain perception, hormonal irregularities and insulin resistance, while the psychological impact of the condition has also been explored. Various treatment regimens have also been the subject of research with varying degrees of success. The heterogeneous nature of the patient population suggests that the mechanistic pathway may be multifactorial, while a comprehensive treatment regimen including both psychosocial and pharmacological interventions may offer the best outcome for patients with cardiac syndrome X.

Adult↗

PubMed2005

Psychosocial factors associated with noncardiac chest pain and cardiac syndrome X.

Cardiac syndrome X, the triad of angina pectoris, positive exercise electrocardiogram (ECG) for myocardial ischemia and angiographically smooth coronary arteries, is associated with increased psychological morbidity, debilitating symptomatology and a poor quality of life. Patients with noncardiac chest pain (NCCP) are often similarly affected. The psychological morbidity noted among this patient population has been linked with a number of psychosocial factors, including impaired social support, traumatic life events, the negative impact of menopause among female sufferers, and an awareness of a family history of coronary heart disease (CHD). Cognitive behavioral therapy (CBT), group support, physical activity and relaxation techniques have been investigated as treatments for psychological morbidity among this patient group with varying degrees of success. While clinicians should be aware of the psychological aspect of patients with NCCP and cardiac syndrome X, further research is needed in order to establish a comprehensive physiological and psychological treatment regimen.

Clinical Trials as Topic↗

PubMed1999

Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire.

BACKGROUND: Prognosis in patients with syndrome X (chest pain and normal coronary arteriograms) is good; however, persistent chest pain and functional disability are common in these patients. Accurate assessment of quality of life may be useful for patient management. AIM: The quality of life status in patients with syndrome X was assessed using a specific questionnaire. This questionnaire was developed and validated for the assessment of quality of life in patients with typical chest pain despite normal coronary arteriograms. METHODS: Ninety consecutive patients were invited to complete both the questionnaire (on two occasions within 2 weeks) and a standardized angina dairy. Fully completed questionnaires were received from 66 (73%) patients (mean age 58 +/- 8 years, 55 women). RESULTS: Answers were scored according to a grading system where higher scores indicate worse quality of life. We observed that total scores increased with severity of angina (Canadian Class I, 38 +/- 16, II: 93 +/- 29, III-IV, 119 +/- 23; p < 0.001) and correlated with both the number and the severity of chest pain episodes (r = 0.50-0.66: p < 0.001). In patients who remained clinically stable (n = 37) during the 2-week assessment, test-retest analysis showed no score differences (87 +/- 30 vs. 81 +/- 30; p = 0.1), while total score increased in patients (n = 24) whose symptoms worsened (108 +/- 31 vs. 116 +/- 31; p < 0.02) and was reduced in those (n = 5) whose symptoms improved (55 +/- 37 vs. 39 +/- 28; p < 0.04). CONCLUSION: Our study shows that quality of life is significantly impaired in patients with syndrome X and that the specific questionnaire used for assessment is a reliable and sensitive tool for the evaluation of quality of life in patients with chest pain and normal coronary arteriograms.

Aged↗

PubMed1999

The effect of aminophylline infusion on the exercise capacity in patients with syndrome X.

Aminophylline was known to decrease effort angina and ischaemia in patients with coronary artery disease and stable angina. This effect has been explained by the antagonization of the vasodilatation caused by adenosine and the prevention of the transmural myocardial maldistribution (steal phenomenon). In this study, treadmill exercise tests (with Bruce protocol) were performed in 14 patients (11 women, 3 men, mean age 51 +/- 9.9 years) diagnosed with syndrome X (typical anginal chest pain, abnormal stress test, normal coronary angiography) before (basal condition) and after the acute i.v. aminophylline infusion (total dosage 6 mg/kg within 15 minutes). It was shown that aminophylline lengthened the time before the occurrence of ischaemia in patients with syndrome X by increasing the ischaemia threshold in spite of the occurrence of tachycardia but it had no effect on the total exercise duration. Aminophylline infusion also exerted a beneficial effect on exercise-induced chest pain. It has been suggested that the role of the adenosine receptor could be important in the pathogenesis of syndrome X.

Aminophylline↗

PubMed1996

[Esophagoscopy in patients with angina pectoris and normal coronary arteriography].

The clinical value of oesophago-gastro-duodenoscopy and distal oesophageal biopsies was investigated in 49 patients with angina pectoris and normal coronary angiograms. The results were compared to 24 hour oesophageal pH-monitoring of the patients and of a control group of 22 healthy sons. Macroscopic esophagitis--mainly grade I was found in 31% of the patients and microscopic oesophagitis in 25%. The only major abnormalities were the identification of three peptic ulcers (6%). Median (range) reflux index was 1.3 (0.0-13.4) in the patient group and 2.1 (0.0-9.9) in the controls (p = 0.49). There were no differences with respect to endoscopical findings or reflux index between patients with a positive and patients with a normal exercise electrocardiogram. At a median 36 months post study 38% of the patients had undergone acid secretion inhibitor treatment with an effect on symptoms in only 4%. The study provides evidence that routine oesophago-gastro-duodenoscopy is of limited value in this patient group.

Adult↗

PubMed1998

Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X.

OBJECTIVES: We sought to investigate whether patients with syndrome X have an abnormal perception of cardiac pain. BACKGROUND: Previous studies have reported an increased sensitivity to potentially painful cardiac stimuli in patients with syndrome X. However, it is not clear whether this increase is due to an increased perception of pain or to an enhanced tendency to complain. METHODS: We assessed cardiac sensitivity to pain in 16 patients with syndrome X and 15 control subjects by performing right atrial and ventricular pacing with increasing stimulus intensity (1 to 10 mA) at a rate 5 to 10 beats higher than the patient's heart rate. False and true pacing were performed in random sequence, with both patients and investigators having no knowledge of the type of stimulation being administered. RESULTS: No control subject had pacing-induced pain; conversely, 8 patients with syndrome X reported angina during atrial pacing (50%, p < 0.01) and 15 during ventricular pacing (94%, p < 0.001). During atrial stimulation, both true and false pacing caused chest pain in a similar proportion of patients (50% vs. 63%, p = 0.61), whereas during ventricular stimulation, true pacing caused chest pain in a higher proportion of patients (94% vs. 50%, p < 0.05). Pain threshold and severity of pain (1 to 10 scale) were similar during true and false atrial pacing, whereas true ventricular pacing resulted in a lower pain threshold (mean +/- SD 3.7 +/- 3.0 vs. 7.9 +/- 2.8 mA, p < 0.001) and a higher level of pain severity (7.3 +/- 2.7 vs. 3.1 +/- 3.5, p < 0.001) than did false pacing. CONCLUSIONS: Patients with syndrome X frequently reported chest pain even in the absence of cardiac stimulation. Yet, in addition to this increased tendency to complain, they also exhibited a selective enhancement of ventricular painful sensitivity to electrical stimulation.

Adult↗

PubMed2001

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X).

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.

Adult↗

PubMed2002

Increased P wave dispersion: a new finding in patients with syndrome X.

The present clinical study was undertaken in patients with syndrome X, namely angina with normal coronary arteries, to investigate the presence of increased P wave dispersion by comparing patients with coronary artery disease (CAD) and healthy control subjects. Three groups were studied - group A, 21 patients (48 6 years) with syndrome X; group B, 16 patients (56 9 years) with CAD; and group C, 16 healthy subjects (49 8 years). Patients with CAD were older than those in groups A and C (P=0.005 and P=0.035, respectively). All groups demonstrated similar PQ, QRS and RR intervals. Group B had a lower minimum P wave duration than group C (P=0.05). P wave dispersion in group A was found to be higher than that in groups B and C (P=0.018 and P=0.0001, respectively). Patients with syndrome X demonstrated increased P wave dispersion compared to patients with CAD and healthy subjects. High sympathetic tone or autonomic imbalance observed in patients with syndrome X may affect intra-atrial and interatrial conduction times, and leave them prone to develop atrial arrhythmias.

Case-Control Studies↗

PubMed1994

Is coronary flow reserve in response to papaverine really normal in syndrome X?

BACKGROUND: An impaired coronary flow reserve in syndrome X has been demonstrated by many studies. Recently, however, a normal coronary flow reserve in response to papaverine was reported, but the number of patients in these studies was small. The aim of this study was to investigate whether coronary flow reserve in response to intracoronary papaverine is really impaired in syndrome X. METHODS AND RESULTS: We investigated 53 syndrome X patients (typical angina, a positive exercise test, and completely normal coronary arteries on angiography) and 26 heart transplant patients with normal coronary arteries (control group). All antianginal medications were stopped 48 hours before the study. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery and was connected to a Millar velocimeter. The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured. Coronary flow reserve was defined as the ratio of hyperemic coronary blood flow velocity in response to papaverine and resting coronary blood flow velocity. The coronary flow reserve (mean +/- SD) in the syndrome X group was 2.72 +/- 1.39. The coronary flow reserve in the control group was significantly higher at 5.22 +/- 1.26 (P < .01). In both groups there was no significant difference in the heart rate or the mean arterial pressure during the study. CONCLUSIONS: Our study shows that coronary flow reserve in response to intracoronary papaverine is impaired in syndrome X patients.

Adult↗

PubMed1999

[Defects in autonomic regulation in myocardial ischemia].

AIM: To evaluate cerebral and peripheral mechanisms of autonomic regulation of the cardiovascular system, their role in development of myocardial ischemia in coronary heart disease (CHD) patients with coronary atherosclerosis and X syndrome. MATERIALS AND METHODS: Psychometric testing, questionnaires, cardiovascular tests (by D. Y. Ewing), automatic spectral analysis of cardiac rhythm variability were used in investigation of psychovegetative regulation in 36 patients and 19 healthy subjects. Group 1 consisted of 26 CHD patients with coronary atherosclerosis and stable angina class I-II. Group 2 consisted of 10 patients with symptoms of myocardial ischemia and coronarographically intact coronary arteries. RESULTS: Patients of both groups demonstrated initial activation of cerebral sympathicoadrenal mechanisms manifesting with high anxiety, depression, vegetative defects in regulation of both initial autonomic tone and autonomic support of the orthostatic test. CHD patients with coronary atherosclerosis were characterized by persistent activation of cerebral sympathicoadrenal mechanisms and resistance of homeostatic baroreflex sympathetic systems. Vagal insufficiency was moderate and arose only at rest. In X syndrome patients with the same initial cerebral activation of the sympathicoadrenal mechanisms had dystonic trend in hemodynamic autonomic parameters: higher systolic blood pressure in subnormal heart rate, lability of baroreflex and cerebral mechanisms under the orthostatic test. The above features of psychovegetative relations make such patients very close to those with psychovegetative syndrome. CONCLUSION: CHD patients with coronary atherosclerosis and patients with X syndrome differ by mechanisms of maladaptation of autonomic regulation.

Adult↗

PubMed1994

Usefulness of changes in exercise tolerance induced by nitroglycerin in identifying patients with syndrome X.

Two exercise tests, one under basal conditions and one after sublingual nitroglycerin (NTG), were performed in 39 patients with stable angina pectoris--16 with critical coronary stenoses and 23 with normal coronary arteries (syndrome X). Under basal conditions, times at ischemic threshold, at peak exercise, and at complete ECG recovery were similar in the two groups. Peak ST depression was significantly higher in patients with coronary artery disease (CAD). In a similar proportion of patients, ST-segment depression developed earlier or at a low heart rate. Patterns of heart rate, blood pressure, and rate-pressure product during exercise and recovery were also similar. After NTG an increase in the ischemic threshold was observed in a significantly higher proportion of patients with CAD (93.8% vs 39.1%). Furthermore, a subgroup of patients with syndrome X showed a worsening of exercise performance. This suggests that NTG does not directly affect small coronary vessels. Our results confirm that no relevant differences exist in exercise responses between patients with CAD and those with syndrome X under basal conditions. NTG-induced changes in this response could be useful in identifying patients with normal coronary arteries. Moreover, this test could be used as a guide to therapeutic approaches.

Administration, Sublingual↗