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PubMed2003

[Long-term outcome in patients with angina-like chest pain and normal coronary angiograms].

BACKGROUND: Short-term prognosis of patients with chest pain and angiographically smooth coronary arteries is good in terms of development of coronary events (fatal or nonfatal myocardial infarction, coronary death, new coronary heart disease), but long-term studies are rare. PATIENTS AND METHODS: 185 consecutive patients (mean age 54 +7.8 years, 59% male)with typical angina pectoris or atypical chest pain who underwent coronary angiography between 1980 and 1989 and had completely normal coronary arteries and left ventricular function (mean ejection fraction 68%) were followed over a period of 12.0 +/- 2.9 years. Exercise tests showed ischemia in 51 patients (ECG) and 21 patients (myocardial scintigraphy), respectively. 173 patients could be recruited for follow-up. RESULTS: One patient died from acute myocardial infarction (0.05% per year). Nine patients died potentially from cardiac causes (0.51% per year) and seven from extracardial diseases. No nonfatal myocardial infarctions were documented. Six patients developed an angiographically documented coronary heart disease with significant stenoses after a mean follow-up of 12.7 years (0.3% per year). These patients had significantly more coronary risk factors than patients without coronary heart disease (2.8 vs. 1.8; p < 0.05) but not more often pathologic findings in rest-ECG (28% vs. 36%; not significant [n.s.]) and exercise test-ing (14% vs. 32%; n.s.). Frequency and intensity of chest pain remained unchanged in 34% of the patients. Symptoms regressed in more patients with an initially negative exercise test compared to patients who had a positive exercise test (78% vs. 54%;p < 0.05). The decrease in patients taking nitrates did not differ significantly between both groups (-42% vs. -27%; n.s.). CONCLUSION: Patients suffering from angina-like chest pain with normal coronary angiograms have a good long-term prognosis which does not differ from the general population of the same age. Patients with positive stress tests will have less relief from their symptoms than patients with a negative stress test over many years.

Adult↗
PubMed1995

Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study.

OBJECTIVES: Our aim was to study the clinical characteristics and evolution of symptoms and left ventricular function in a clinically homogeneous group of patients with syndrome X (angina pectoris, positive exercise test results and normal coronary arteriograms). BACKGROUND: The syndrome of angina with normal coronary arteriograms is heterogeneous and encompasses different pathogenetic entities. These characteristics may contribute to the existing controversy concerning the cause of syndrome X. METHODS: We studied 99 patients with syndrome X (78 women, 21 men; mean age +/- SD 48.5 +/- 8 years). All underwent clinical characterization, ambulatory electrocardiographic (ECG) monitoring and echocardiographic assessment of left ventricular function during a follow-up period of 7 +/- 4 years. RESULTS: The syndrome was more common in women than in men. Of the women, 61.5% were postmenopausal before the onset of chest pain. All 99 patients had exertional angina, and 41 also had rest angina. The average duration of episodes of chest pain was > 10 min in 53% of patients. Sublingual nitrate was effective for relief of pain in 42% of patients. Transient ST segment depression was observed during ambulatory ECG monitoring in 64 patients and myocardial perfusion abnormalities in 22. During the first stage of the exercise test, 32 patients had an increase > 20 mm Hg in systolic blood pressure and showed an earlier onset of ST depression and shorter exercise time than did patients whose blood pressure increased < or = 20%. During follow-up, no deaths or myocardial infarctions occurred, ventricular function was unchanged (shortening fraction 35.4 +/- 4% vs. 35.6 +/- 3%; heart failure developed in only one patient), systemic hypertension occurred in eight patients and conduction disturbances in four. Symptoms lessened in 11 patients, were variable or unchanged in 64 and worsened in 24. CONCLUSIONS: Syndrome X, as defined in this study, occurs predominantly in postmenopausal women. Patients usually have chest pain typical for angina, but conventional antianginal treatment is not often successful. Myocardial perfusion abnormalities occur in a small proportion of patients. Long-term survival is not adversely affected, and deterioration of cardiac function rarely occurs.

Adult↗
PubMed2001

The higher likelihood of developing cardiomegaly during follow-up in patients with syndrome X and abnormal thallium-201 myocardial perfusion SPECT.

'Syndrome X' describes patients with exertional chest pain and a normal coronary arteriogram. In some patients, acute myocardial ischemia can be demonstrated by regional myocardial perfusion defects on thallium-201 exercise test. However, some patients with typical angina have normal perfusion on thallium-201 heart scintigraphy. It is not clear whether there are different prognoses for patients with normal and abnormal thallium studies. In this study, the clinical features, long term follow-up and clinical results of syndrome X patients with normal and abnormal thallium studies were evaluated to determine the differences between these two groups. Fifty-nine patients (52 males, seven females, mean age 62+/-6 years) with syndrome X were enrolled and divided into two groups on the basis of results of thallium-201 heart scintigraphy. Group I was comprised of 22 patients with normal thallium-201 perfusion scan and group II was comprised of 37 patients with abnormal thallium-201 heart scan. All subjects received coronary arteriography, exercise test, thallium-201 myocardial SPECT, ejection fraction of left ventricle, echocardiography, blood analysis and long term follow-up with questionnaire for 10 years. Lower maximal rate-pressure product and higher angina scores were found in group II. More patients developed cardiomegaly (nine of 33 patients) in group II than in group I (one of 21 patients). Both groups, however, were at low risk for cardiac events (cardiac death or myocardial infarction).

Aged↗
PubMed2005

[Typical angina pectoris complaints without coronary macroangiopathy].

HISTORY AND CLINICAL FINDINGS: A 46-year-old patient with repetitive chest pain on exercise and exclusion of coronary heart disease was transferred for further diagnostic evaluation and therapy because of the suspicion of cardiac syndrome X. INVESTIGATIONS: Coronary angiography showed no evidence for a stenotic coronary heart disease. However, a decreased coronary blood flow reserve was detected upon adenosin treatment (RCA), and myocardial scintigraphy (single-photon emission tomography-investigation [SPECT]) revealed a perfusion defects in the inferior wall. TREATMENT AND COURSE: Endothelial dysfunction (syndrom X) was diagnosed and an optimised therapy regime was initiated in order to improve endothelial function. CONCLUSION: In patients with typical angina pectoris and positive treadmill exercise stress test in the absence of stenotic coronary heart disease, cardiac syndrome X should be considered, and further invasive- and non-invasive tests should be performed. Therapeutic goals should be to improve endothelial function and to control chest pain and improve quality of life.

Chest Pain↗
PubMed1994

[Incidence of myocardial bridges after adrenergic stimulation and decreasing afterload in patients with angina pectoris, but normal coronary arteries].

The prevalence of myocardial bridging in patients with angina pectoris but normal coronary arteries was evaluated in 1780 patients who consecutively underwent coronary angiography. 62 patients (3.5%) were free of coronary atherosclerosis or other organic heart disease. In four of these patients systolic narrowing of the LAD was present. The other 58 patients received 0.2 mg nitroglycerin (NTG) intracoronarily and 30 micrograms/ml orciprenalin (ORC) intravenously up to a heart rate of 130/min. Repeated angiography revealed systolic compression of the LAD due to myocardial bridging (MB) in 40% (25 of 62). The length of MB raised from 1.4 +/- 0.9 cm to 2.1 +/- 1.1 cm (p < 0.001) after NTG and to 2.8 +/- 1.1 cm (p < 0.001) after ORC. Coronary luminal stenosis increased from 48 +/- 29% to 67 +/- 25% after NTG (p < 0.001) and to 83 +/- 18% (p < 0.001) after ORC. The prevalence of myocardial bridging in 40% of patients with stress-induced angina pectoris but normal coronary arteries is high. Nearly always coronary compression by myocardial bridging is only evident after adrenergic stimulation or after afterload reduction. Therefore, NTG and ORC are useful drugs to facilitate diagnosis of myocardial bridging by increasing coronary compression.

Adult↗
PubMed1998

Effects of doxazosin on exercise-induced angina pectoris, ST-segment depression, and insulin sensitivity in patients with syndrome X.

A significant proportion of patients with cardiac syndrome X have impaired coronary vasodilator capacity, which is thought to be caused by an increased sympathetic drive. The alpha1-adrenoceptor blocker, doxazosin, increases the coronary vasodilator reserve in patients with syndrome X. To study whether the augmentation is associated with clinical improvement in patients, we conducted a double-blind, placebo controlled, crossover study with doxazosin 1 to 4 mg once daily for 10 weeks in 16 patients with syndrome X (14 women and 2 men; mean +/- SD age 56+/-5 years). Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression during bicycle exercise testing were compared after treatment with doxazosin 2 mg or placebo for 5 weeks and again after treatment with doxazosin 4 mg or placebo for 10 weeks. Insulin sensitivity was assessed by the minimal model after 10 weeks of doxazosin or placebo treatment. Twelve patients completed the protocol. Doxazosin 4 mg/day decreased systolic blood pressure at rest (109+/-16 vs 125+/-18 mm Hg, p <0.05) and increased basal heart rate (85+/-9 vs 76+/-11 beats/min, p <0.05), whereas hemodynamics were unaffected during exercise. Time to angina, exercise duration, time to 0.1 mV ST-segment depression, and maximal ST-segment depression were similar during treatment with doxazosin and placebo irrespective of the doxazosin dose. Insulin sensitivity was not different with doxazosin and placebo. In conclusion, alpha1 blockade does not significantly improve exercise duration, angina pectoris, and ST-segment depression despite a favorable vasodilator effect in patients with syndrome X. The absent clinical efficacy of doxazosin may challenge the use of the coronary vasodilator capacity as an appropriate method to subclassify patients with syndrome X.

Adrenergic alpha-Antagonists↗
PubMed1997

[Angina pectoris with normal coronary arteries].

The occurrence of angina pectoris in patients with normal coronary angiograms is a subject of investigation since its first description as an entity in 1967. Its etiology remains unknown but, in the absence of disease of the epicardial coronary arteries, dysfunction of the small, most distal vessels and the endothelium appear to be incriminated. In this review, the most recent knowledge and understanding of the pathophysiology, clinical presentation and management of this syndrome is presented.

Coronary Vessels↗
PubMed1998

Role of the central endogenous opiate system in patients with syndrome X.

BACKGROUND: To evaluate the role of the endogenous opioid system (EOS) in abnormal pain perception in patients with syndrome X, we used a neuroendocrine approach, evaluating plasmatic luteinizing hormone (LH) changes after naloxone, a competitive antagonist of opioid receptors able to unblock tonic EOS inhibition on gonadotropin release. Thus LH response to naloxone test indicates the central EOS activity on hypothalamic luteinizing hormone-releasing hormone (LH-RH) inhibitory opioid receptors. METHODS: Ten patients with syndrome X, 10 age-matched male patients with coronary artery disease (CAD), and 10 normal subjects were analyzed. Naloxone tests were performed between 8 and 9 am. Basal beta-endorphin and LH levels were determined on 4 blood samples at 20-minute intervals; after naloxone (0.1 mg/kg intravenously in 4 minutes), LH was measured on 8 samples at 15-minute intervals. In all patients the test was also performed after LH-RH administration. Anginal pain on exercise testing was subjectively scored on a 1 to 10 analogic scale and wall motion abnormalities were quantified by a wall motion score index. RESULTS: Significant differences were found in LH release after naloxone (CAD 260.3 +/- 42.6 vs syndrome X 151.6 +/- 48.5 mIU/mL, P <.05), angina score (CAD 5.5 +/- 1.3 vs syndrome X 7.2 +/- 1.7, P <.05), and wall motion abnormalities (CAD 3.6 +/- 1. 2 vs syndrome X 2.8 +/- 1.9, P <.05). CONCLUSIONS: The reduced LH release after naloxone in syndrome X, with a normal LH-RH response, suggests a lower central EOS activity, which may be related to the higher anginal pain perception.

Humans↗
PubMed2004

Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X.

Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.

C-Reactive Protein↗
PubMed2005

Angiotension-converting enzyme gene I/D polymorphism in patients with angina and normal coronary arteriograms.

A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).

Alleles↗
PubMed1995

Syndrome X--angina and normal coronary angiography.

It is clear that angina pectoris with normal coronary arteries is a heterogeneous and ill-defined syndrome that encompasses different pathogenic entities. Differences in patient selection and in definition of 'syndrome X' has made comparison between different study groups rather difficult. Two decades of investigations have not revealed a specific cause of this syndrome. There is now a general belief that syndrome X probably encompasses several pathophysiological disease entities and the mechanisms involved in syndrome X remain to be fully elucidated.

Chest Pain↗
PubMed1997

Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging.

PURPOSE: To demonstrate the feasibility of determining myocardial blood flow changes and the myocardial perfusion reserve with magnetic resonance (MR) first-pass imaging, to validate the MR results by means of comparison with radiolabeled microsphere flow measurements in an animal model, and to compare the coronary flow reserve with the perfusion reserve at MR imaging in patients with hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging with contrast agent enhancement was performed in eight pigs with acute ischemia and in eight adult patients (six women, two men). In the pigs, microsphere flow measurements were obtained in parallel with the MR measurements. In the patients, the coronary flow reserve was measured with an intracoronary Doppler flow ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the animal studies, there was linear correlation between MR perfusion indexes and the microsphere flow measurements (r = .88, P < .01). In the patients, the regional perfusion reserve matched the coronary flow reserve (linear regression with a slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve can be quantified with first-pass MR imaging. In patients with microvascular dysfunction, the myocardial perfusion reserve matches the reduced coronary flow reserve.

Animals↗
PubMed1996

Beneficial effect of treatment with transdermal estradiol-17-beta on exercise-induced angina and ST segment depression in syndrome X.

We investigated the acute effect of transdermal estradiol-17-beta on exercise-induced ischemia in 15 postmenopausal women (mean age 58 +/- 6 years) with syndrome X (angina pectoris, positive exercise test and normal coronary angiogram) and eight healthy women (mean age 58 +/- 5 years) in a placebo-controlled, double-blind crossover trial. Two exercise tests were performed on separate days, separated by at least 1 week, after application of placebo or 100 micrograms/24 h estradiol-17-beta. In the control group there was no difference between estradiol and placebo. Patients with syndrome X, on the other hand, showed an increased time to angina (323 +/- 99 versus 233 +/- 67 s, P = 0.0044), time to 1 mm ST depression (257 +/- 142 versus 187 +/- 122 s, P = 0.039), total exercise time (363 +/- 104 versus 323 +/- 85 s, P = 0.038), and working capacity (93 +/- 17 versus 89 +/- 15 W, P = 0.0086) during active treatment. In conclusion, estradiol-17-beta has a beneficial effect on myocardial ischemia in postmenopausal women with syndrome X and may be a useful therapeutic agent in this disease.

Administration, Cutaneous↗
PubMed2005

Mean platelet volume in the patients with cardiac syndrome X.

BACKGROUND: Angina with normal coronary arteries, cardiac syndrome X, is a diagnosis of exclusion. The exact mechanism of this clinical syndrome remains unclear. Although the prognosis is as good as equal to that of normal population, symptoms related with the syndrome impair largely quality of life. Mean platelet volume showing the platelet size is an indicator of platelet function. Larger platelets are more active than smaller ones. METHODS AND RESULTS: We designed a study, evaluated mean platelet volume of the patients with cardiac syndrome X (group A) and stable angina (group B) and investigated the relation between groups. Eighty patients with cardiac syndrome X with a mean age of 51.08 +/- 9.79 years and 67 patients with stable angina with a mean age of 55.16 +/- 11.96 years were studied. At the end of the study, mean platelet volume of group A was significantly higher than that of group B, 10.55 +/- 1.08 fl vs. 9.39 +/- 0.58 fl, respectively (P < 0.001). CONCLUSION: Raised platelet size has been shown to be associated with adverse cardiac events. Mean platelet volume has increased in acute coronary syndromes and also in cardiac syndrome X in our study. Life style modification may optimize platelet size and improve symptoms in these patients.

Adult↗
PubMed1996

[The correlation between the clinical characteristics and psychological status in syndrome X patients].

Patients with anginal symptoms and normal coronary arteries have been found to present with high levels of neuroticism i.e. anxiety, depression and somatic concerns. Whether neuroticism plays a role in precipitating coronary hypoperfusion and symptoms is still a matter of investigation. The present study was undertaken to assess the relation between psychological status and clinical symptoms in 22 patients with syndrome X (angina and ST depression with angiographically normal coronary arteries and reversible myocardial perfusion abnormalities). Neuroticism was evaluated by Beck Depression Inventory, Hamilton Anxiety Rating Scale (HAM-A), State-Trait Anxiety Inventory, Sheehan Patient Rated Anxiety Scale, State-Trait Anger Expression Inventory (STAXI), Brief Psychiatric Rating Scale and Clinical Global Impression. Data were compared with those obtained in 30 patients with stable angina as well as coronary artery disease. All patients underwent an exercise stress testing and a 24-hour ambulatory Holter monitoring. Patients with syndrome X scored significantly higher than stable angina (p < 0.05 each) on all psychological tests but STAXI. No significant differences, between syndrome X and stable angina were found in exercise stress testing parameters and during Holter monitoring. Twelve out of 22 syndrome X patients had a score > 28 in HAM-A (Group 1, with frank psychiatric abnormalities). The remaining 10 patients were labelled as Group 2. No significant differences between Group 1 and Group 2 were found in exercise capacity (time to 0.1 m V ST depression: 397 +/- 73 and 419 +/- 137 s, respectively; NS) or in the number of anginal episodes per day (0.9 +/- 1.3/24 hours and 0.6 +/- 0.8/24 hours respectively; NS). In contrast, Holter monitoring showed a significantly higher number of ischemic episodes in Group 1 than in Group 2 (1.6 +/- 1.7 vs 0.1 +/- 0.3/24 hours; p < 0.02) and a greater duration of ischemia (23.8 +/- 32 vs 0.3 +/- 1 min/24 hours; p < 0.03). We conclude that: patients with syndrome X evidence elevated neuroticism scores; a high degree of anxiety correlates with increased transient myocardial ischemia during daily life; neuroticism may itself cause changes in coronary microvascular function in syndrome X. Alternatively it may simply modulate the threshold for ischemia in the presence of underlying dysfunction.

Adult↗
PubMed2000

Negative stress echocardiographic responses in normotensive and hypertensive patients with angina pectoris, positive exercise stress testing, and normal coronary arteriograms.

OBJECTIVES: To systematically compare the results of dobutamine stress echocardiography in matched groups of hypertensive and normotensive patients with anginal chest pain and normal coronary arteriograms (CPNA). SETTING: University hospital. SUBJECTS: 33 patients with exertional anginal chest pain, a positive exercise stress ECG, and a completely normal coronary arteriogram; 17 had a history of systemic hypertension (14 women; mean (SD) age 57 (6) years), and 16 had no hypertensive history (12 women; age 54 (9) years). METHODS: Ambulatory ECG monitoring, dobutamine stress echocardiography, and thallium-201 single photon emission computed tomography (SPECT) were performed in all subjects. RESULTS: All patients had normal left ventricular systolic function at rest and none fulfilled the criteria for ventricular hypertrophy. Eight normotensive patients and 10 hypertensive patients had perfusion abnormalities on thallium SPECT (p = 0.61). Dobutamine infusion reproduced anginal pain in seven normotensive and seven hypertensive patients (p = 0.88). ST segment depression was also recorded in eight normotensive patients and seven hypertensive patients (p = 0. 61). No patient in either group developed regional wall motion abnormalities during dobutamine stress echocardiography. CONCLUSIONS: Neither hypertensive nor normotensive CPNA patients developed regional wall motion abnormalities during dobutamine stress echocardiography, despite the high prevalence of scintigraphic perfusion defects in both groups and the presence of chest pain and ST segment depression. Thus myocardial ischaemia was not present in either group, or else dobutamine stress echocardiography is insensitive to ischaemia caused by microvascular dysfunction.

Aged↗
PubMed1999

Left ventricular dysfunction during dobutamine stress echocardiography in patients with syndrome X and positive myocardial perfusion scintigraphy.

AIMS: A sizeable proportion of patients with angina, angiographically smooth coronary arteries and positive exercise test (syndrome X) have stress/rest myocardial perfusion defects. The aim of the study was to assess whether perfusion defects are dependent upon a reduction in coronary flow reserve causing regional left ventricular dysfunction in syndrome X patients. METHODS AND RESULTS: Twenty-two syndrome X patients underwent dobutamine stress echocardiography (DSE). All had stress-induced perfusion defects documented by 99m-Tc-MIBI scintigraphy. Resting and peak DSE wall motion score index (WMSI) were evaluated. Six patients exhibited resting wall motion abnormalities in 10 segments (WMSI 1.05 +/- 0.11). DSE was positive in 12 patients (53%), in whom 16 myocardial segments were involved: of these, 12 were normokinetic and 4 hypokinetic at rest. Peak WMSI was 1.17 +/- 0.17 (p < 0.05 vs rest). Of the 12 patients with a positive DSE, 9 also showed diagnostic ECG changes and 6 complained of angina. Of the 10 patients with negative DSE, 5 had angina and 5 (one with angina) showed ECG changes. In 7 patients (7 segments) (32%), the location of dobutamine-induced wall motion abnormalities coincided with the area where exercise-induced hypoperfusion was observed with MIBI. CONCLUSIONS: More than a half of syndrome X patients with myocardial perfusion abnormalities also develop regional LV dysfunction during DSE. However, the site of perfusion defects and wall motion abnormalities can be different. Reversible ischemia, defined as a parallel limitation of flow reserve and inducible dysfunction, could be identified as the cause of chest pain in almost one-third of patients.

Adult↗
PubMed1994

Acute effects of nitrates on exercise testing in patients with syndrome X. Clinical and pathophysiological implications.

BACKGROUND: Sublingual nitrates are much more effective in relieving angina pectoris in patients with coronary artery disease than in patients with syndrome X, but it is not known whether their effect on exercise tolerance is also different in these two groups of patients. METHODS AND RESULTS: Treadmill exercise testing was performed before and after administration of sublingual isosorbide dinitrate (ISDN, 5 mg) in 18 patients with syndrome X (effort angina and normal coronaries, group X) and in 33 patients with documented coronary artery disease (group C). As a selection criterion, all patients had ST-segment depression > or = 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed during the exercise test after administration of ISDN were (1) heart rate at 1-mm ST-segment depression was higher (126 +/- 25 versus 104 +/- 15 beats per minute [bpm], P < .01) in group C, whereas it was not different (125 +/- 15 versus 126 +/- 16 beats per minute) in group X; (2) the rate-pressure product at 1-mm ST-segment depression, the time to 1-mm ST-segment depression, and the exercise duration were significantly improved in group C (P < .01 for all) but were worsened in group X (18,047 +/- 4159 versus 20,535 +/- 4507 bpm . mm Hg, P = .014; 268 +/- 312 versus 429 +/- 214 seconds, P < .01; 494 +/- 279 versus 622 +/- 194 seconds, P = .013, respectively); (3) a normalization of the ECG (no ST-segment depression) was obtained in 10 patients (30%) of group C but in only 1 (5%) of group X (P < .01); (4) angina was prevented in 10 of 19 patients of group C but in no patient of group X (P < .01). CONCLUSIONS: In patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise testing appear to be clinically useful to distinguish patients with coronary artery stenoses from patients with syndrome X. Indeed, worsening of exercise tolerance is highly predictive of normal coronary arteries. Furthermore, the failure of nitrates to improve exercise tolerance in patients with syndrome X suggests that a deficiency in coronary prearteriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome.

Aged↗