Vasospastic angina with angiographically normal coronary vessels of iatrogenic origin. Apropos of 2 cases]

Two cases of angina pectoris, induced by methylergometrine (Methergin) and by an association of ergotamine tartrate (Gynergene) and methysergide (Desernil) respectively, are reported. In both patients, angiography revealed spontaneous spasm in a coronary system free from any significant atheromatous stenosis. In the second case, a test administration of i.v. Methergin, administered during calcium-channel antagonist treatment a few days after the "guilty" drugs had been stopped was found to be negative. The outcome was favorable in both cases: the angina disappeared and the base-line and exercise ECG returned to normal. The hypothesis of coronary spasm induced by the treatment was adopted in both cases. In this context, the major iatrogenic etiologies of vasospastic angina are recalled, together with the prophylactic and therapeutic measures they call for.     

Myocardial metabolism in angina with angiographically normal coronary arteries

Myocardial metabolism was studied during rapid atrial pacing in 22 patients with angina and angiographically normal coronary arteries. Pyruvate, non esterified fatty acid and lactate levels were measured in the coronary arteries and veins under basal conditions, at the peak of atrial pacing and during the recovery phase. A control group of 8 patients had neither angina, ST depression, or lactate production during atrial pacing. A correlation was observed between the coronary arterio-venous difference and arterial pyruvate and non esterified fatty acid levels in the 22 patients during the 3 periods of study. The control patients did not differ significantly from the rest of the population. There was a correlation between the coronary arterio-venous difference and arterial lactate levels under basal conditions in all of the study and control groups. This correlation remained significant during atrial pacing and the recovery period only in the control group. It was possible to distinguish a group of 14 patients (64 p. 100) (Group A) with a correlation coefficient of lactate production similar to the control group (+/- 2 standard deviations) during atrial pacing, from a second group of 8 patients (36 p. 100) (Group B) with abnormal myocardial metabolism. The arterial lactate concentrations were similar in both groups in the 3 periods of study. A coefficient of lactate extraction less than 10 p. 100 was observed in 2 patients in Group A and in 7 patients in Group B (88 p. 100, p less than 0.01). One patient in Group B had a coefficient of lactate extraction greater than 10 p. 100 (+ 13 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)     

Infarction with angiographically normal coronary vessels. (20 cases)

Over 8 years, 20 cases of infarction with normal coronary angiography have been reported, representing 0.9% of the patients who underwent a coronary angiography after a myocardial infarction. The main characteristics of these patients are compared with those taken from the literature. The occurrence of this disease mainly depends on the age: especially higher when the patients are younger, ranging between 1 and 4% in major series, but it may reach 25% in case of infarction occurring before the age of 30. Therefore, this entity mainly affects young patients (mean age in the literature: 34.3 years), with a large proportion of women (27%). The main risk factor is smoking, found in 3 out of 4 men an more than half of the women; on the contrary, hypercholesterolemia and arterial hypertension are only seldom found. In women, administration of estro-progestative medications in mentioned in almost every other case. Coronary heredity is mentioned in one out of 3 cases. In 68% of the cases, the infarction is the original manifestation and frequently occurs during stress: 60 p. cent of the cases. The site of the necrosis is insignificant. Mortality is low: 2 p. cent but in 5 p. cent of the cases, the course may be complicated by recurrence or heart failure. According to recent findings on coronary angiography during the acute phase, the pathogenesis could involve an arterial coronary thrombosis, perhaps developing on minimal coronary lesions, caused by a spasm and/or a platelets hyperaggregation; then this coronary thrombosis is revascularized.     

Coronary flow reserve, esophageal motility, and chest pain in patients with angiographically normal coronary arteries

PURPOSE AND METHODS: To ascertain the relative prevalence of abnormalities of coronary flow reserve and esophageal function in patients with chest pain despite angiographically normal coronary arteries, 87 patients underwent invasive study of coronary flow reserve and, during the same week, esophageal testing. RESULTS: Sixty-three of the 87 patients (72%) demonstrated abnormalities of coronary flow reserve, as evidenced by an increase in coronary resistance during the stress of rapid atrial pacing after administration of ergonovine 0.15 mg intravenously (1.33 +/- 0.36 mm Hg.minute/mL), compared with pacing at the same heart rate before ergonovine administration (1.10 +/- 0.33 mm Hg.minute/mL). This higher coronary vascular resistance occurred in the absence of significant epicardial coronary artery luminal narrowing. Fifty-seven of these 63 patients (90%) with a coronary vasoconstrictor response to ergonovine described their typical chest pain during pacing stress, compared with only six of 24 patients (25%) who demonstrated no coronary flow abnormality (p less than 0.001). After administration of dipyridamole 0.5 to 0.75 mg/kg intravenously to 65 patients, the 48 patients with ergonovine-induced vasoconstriction had a significantly higher minimum coronary resistance, compared with the 17 patients without a coronary vasoconstrictor response to ergonovine (0.65 +/- 0.21 versus 0.47 +/- 0.13 mm Hg.minute/mL, p less than 0.03). Twenty of 87 patients (23%) had abnormal esophageal motility [nutcracker esophagus (11), nonspecific motility disorder (seven), and diffuse esophageal spasm (two)], including 16 of the 63 patients (25%) with abnormal coronary flow reserve. Twenty-four (28%) patients experienced their typical chest pain during motility testing, but only five of these patients met criteria for abnormal esophageal motility. Nine of 75 patients tested (12%) had their typical chest pain during Bernstein testing, and 18 of 38 patients (47%) tested had their typical chest pain provoked by intraesophageal balloon distention. CONCLUSIONS: Seventy-one of 87 patients (82%) with anginal-like chest pain and normal epicardial vessels in our series had a disorder of either coronary flow reserve, esophageal motility, and/or reproduction of typical chest pain during acid infusion. Of interest, chest pain was commonly encountered during cardiac and esophageal testing (85% of patients), regardless of the ability to demonstrate an abnormality of coronary flow reserve or abnormal esophageal function. This suggests that pain experienced by these patients may be a consequence of myocardial ischemia, esophageal dysfunction, abnormal visceral nociception, or a combination of any or all of these entities.     

Evaluation of coronary reserve in angina pectoris with angiographically normal coronary arteries

Coronary reserve was studied: 1) during rapid atrial pacing and then, 2) during dipyridamole infusion (0.6 mg/Kg/4 min) in 3 groups of subjects: 13 patients with angina pectoris and angiographically normal coronary arteries (ANC) with proven myocardial ischaemia during atrial pacing, 15 patients with coronary artery disease (COR) and 17 normal controls with normal coronary angiography and atrial pacing. Coronary sinus flow (QCS) was measured by thermodilution and myocardial metabolism studied by the coefficient of lactate extraction (K). At maximal pacing rates, K remained 15 p. 100 in the control group (average 24 +/- 7 p. 100) but was inversed in the ANC (-3 +/- 10 p. 100) and COR groups (-27 +/- 38 p. 100). The risk in QCS was low in the COR group (+60 +/- 33 p. 100) p less than 0.02, but significant in the ANC group (+104 +/- 57 p. 100) and normal controls (+107 +/- 41 p. 100). Coronary reserve, calculated as the percentage increase in QCS with dipryridamole, was found to be the same in the ANC group (+225 +/- 79 p. 100) as in normal subjects (+191 +/- 81 p. 100) but was low in the COR group (74 +/- 42 p. 100, p less than 0,001). Therefore, no reduction in coronary reserve was shown in patients with angina and normal coronary arteries whilst the myocardial ischaemia in coronary disease does seem to be related to an amputation of the coronary reserve.     

Long-term clinical course of patients with angina and angiographically normal coronary arteries

In 88 of 103 consecutive patients with angina and normal coronary arteries, follow-up data could be achieved 6-11 years (9.2 +/- 1.2 years) after diagnostic left heart catheterization. Three of these patients died during follow-up (two noncardiac deaths and one death with no identifiable etiology). One patient suffered a documented myocardial infarction. In 40 patients (47%) chest pain diminished, while symptoms were unchanged in 20 (24%) or even worse in 25 (29%). Resolution or persistence of chest pain could not be predicted either by the character of pain (typical vs. atypical), the presence of hypertension, a left bundle-branch block, a positive exercise electrocardiogram or pathological pulmonary artery pressures during exercise, documentation of myocardial bridges, local wall motion abnormalities, or a left ventricular end-diastolic pressure greater than or equal to 13 mmHg. However, continuing chest pain was significantly more common in patients who revealed a 'slow-flow phenomenon' at initial coronary arteriogram. Thus, in patients with angina and normal coronary arteries the long-term course regarding frequency of morbid cardiac events is benign. However, more than half of the patients reported chest pain to be similar or even worse than at catheterization. Most clinical and invasive results at initial evaluation had no predictive value for the persistence of symptoms. The impact of 'slow-flow' in coronary arteriography, which was a phenomenon almost exclusive to patients with constant or even worse chest pain at follow-up, should be evaluated in larger patient populations.     

Spontaneous rupture of the papillary muscle with angiographically normal coronary vessels

Papillary muscle rupture is an unusual pathology, commonly being a mechanical complication of an acute myocardial infarction or a blunt chest trauma. In this case report we describe a patient with a spontaneous complete posteromedial papillary muscle rupture, secondary to an isolated papillary muscle infarction, in the absence of coronary artery disease, resulting in severe mitral regurgitation, cardiogenic shock and uneventful urgent mitral valve replacement. The clinical and histopathologic literature, and mechanisms to explain this kind of rupture, are reviewed.     

The ergometrine test: effects on esophageal motility in patients with chest pain and normal coronary arteries

Ergometrine can evoke coronary spasm in patients with variant angina. The cause of ergometrine-induced chest pain in the absence of coronary spasm is not clear. To determine whether ergometrine produced esophageal dysfunction and chest pain, we evaluated 28 patients by esophageal manometry. Six had chest pain in response to ergometrine during cardiac catheterization (group I) and 22 did not (group II). Results of cardiac catheterization were normal in all patients. Seven volunteers with no history of chest pain formed a control group (group III). Esophageal manometry was performed before and after ergometrine administration (0.4 mg I.V.). Ergometrine provocation during esophageal manometry caused significant deterioration in esophageal motility associated with familiar pain in 5/6 group 1 patients. The motility disorders were characterized by repetitive contracts of high amplitude and long duration in the distal esophagus. No patient from group II or III experienced chest pain after ergometrine and only 2 from group II developed long duration contractions. Thus, we conclude that in patients with normal coronary angiograms, ergometrine-induced chest pain without associated coronary spasm suggests that esophageal motility disorders originate chest pain.     

Acute myocardial infarction with angiographically normal coronary arteries.

The authors present the case of a 51-year-old woman, with no known cardiovascular risk factors, admitted with anterior acute myocardial infarction complicated by primary ventricular fibrillation, who underwent reperfusion therapy with tenecteplase. Left heart catheterization on the sixth day showed left ventricular anteroapical akinesia and normal coronary arteries. The causes of acute myocardial infarction with normal coronary arteries and its differential diagnosis are discussed.     

Clinical significance of the calcification of coronary arteries in patients with angiographically normal coronary arteries.

In order to clarify the clinical significance of coronary calcification in patients with angiographically normal coronary arteries, exercise electrocardiography was used and left ventricular function was examined noninvasively and invasively. The patient groups were as follows: (1) patients with coronary artery calcification on only the left anterior descending artery but no narrowing lesion on any other arteries (calcified group), (2) patients with a significant stenosis on only the left anterior descending artery (stenotic group), and (3) the control group. The left ventricular function in the calcified group, as indicated by systolic time intervals and invasive parameters such as ejection fraction and mean systolic ejection rate, showed a depression similar to that in the stenotic group, compared with the control group. The incidence of electrocardiographically ischemic responses to exercise testing was significantly higher in the calcified group (75%, p less than 0.01) and the stenotic group (68%, p less than 0.01) than in the control group (25%). Exercise tolerance time and the maximum double product were markedly smaller in the calcified and the stenotic groups as compared with the control group. These results indicate that the left ventricular function and coronary reserve in the calcified group were reduced and almost identical with those in the stenotic group. The authors conclude that a calcified coronary artery, even if patent, cannot supply an adequate blood flow for the myocardium, resulting in impaired left ventricular function.     

Methergin testing with angiographically normal coronary arteries

To evaluate the incidence of spasm in patients with angiographically normal coronary arteries or with stenosis less than or equal to 50%, methergin testing was done consecutively in 1,200 patients (742 men and 458 women). The methergin test was performed 850 times during coronary angiography and 350 times after it. The test was globally positive in 11% (127 of 1,200 patients), positive in 7% among 921 patients presenting with atypical chest pain, 13% of 31 patients with effort angina, 54% of 54 with angina at rest, 57% of 53 with Prinzmetal's angina, 3% of 59 with acute myocardial infarction and 1% of 82 miscellaneous patients without chest pain. Another test was done in 291 patients after blockade of the cardiac autonomous nervous system with 0.04 mg/kg of atropine and 2 mg/kg of labetolol. The frequency of positive results in the methergin test increased after blockade from 8 to 19% (p less than 0.01). The increase of positive results was especially obvious among patients with atypical chest pain (from 6 to 14%). Thus, frequency of spasm in these patients with normal coronary arteries or without significative lesions was 11%. This incidence was influenced by the composition of the patient population and increased with blockade of the cardiac autonomous nervous system.     

Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.     

Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries

Angiographically normal coronary arteries are found in a substantial number of patients evaluated for angina pectoris. One third to one half of such patients demonstrate abnormalities of myocardial perfusion or metabolism when evaluated with invasive techniques. This study was designed to determine whether angina in such patients is attributable to abnormalities of perfusion at rest, maximal perfusion or vasodilator reserve and whether any identified abnormalities were global or regional in nature. Positron emission tomography was performed with oxygen-15-labeled water (H2(15)O) and oxygen-15-labeled carbon monoxide (C15O) before and after intravenous dipyridamole to assess regional myocardial perfusion and perfusion reserve in absolute terms in 16 normal subjects and 17 patients with chest pain and angiographically normal coronary arteries. Eight of the 17 patients had a myocardial perfusion reserve less than 2.5 (the lower limit of normal in studies with positron emission tomography, as well as with other techniques) and 9 of 17 patients had a normal response. In the patients with an impaired perfusion reserve, perfusion at rest was significantly higher than that measured in normal subjects (1.61 +/- 0.38 versus 1.25 +/- 0.28 ml/g per min, p less than 0.02) and maximal flow and perfusion reserve were significantly reduced (2.26 +/- 0.92 versus 4.62 +/- 1.58 ml/g per min and 1.4 +/- 0.5 versus 3.8 +/- 1.1, respectively; p less than 0.001 for both comparisons). Abnormalities of perfusion and perfusion reserve were spatially homogeneous without detectable regional disparities. Thus, nearly half of patients with chest pain and normal coronary arteries have abnormalities of myocardial perfusion that are detectable noninvasively with positron emission tomography and H2(15)O.     

Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms

This study determines whether an impaired endothelium-mediated vasodilation in coronary resistance vessels exists in patients with microvascular angina. In 23 patients with clinically suspected coronary artery disease and smooth coronary arteries in the angiogram, coronary flow in response to an endothelium-related (acetylcholine) and endothelium-unrelated (dipyridamole) vasodilation was measured. Coronary flow was determined by the gas-chromatographic argon method (1) before, (2) with intracoronary acetylcholine infusion, and (3) after dipyridamole administered intravenously. In 8 patients, acetylcholine did not significantly increase coronary flow (from 91 +/- 28 to 118 +/- 37 ml/min.100 g), whereas flow was greatly increased after administration of dipyridamole (258 +/- 97 ml/min.100 g), indicating an endothelium-related vasodilator defect. In 6 patients, neither acetylcholine nor dipyridamole caused a significant increase in coronary flow, indicating an impaired coronary vasodilation on the vascular site. In 6 patients, coronary flow increased markedly after both administration of both acetylcholine and dipyridamole (from 81 +/- 26 to 191 +/- 68 and 234 +/- 87 ml/min.100 g). In 3 patients given acetylcholine, coronary artery constriction occurred. No significant correlation was found between the response to acetylcholine and that to dipyridamole (r = 0.40, p = not significant). The results indicate that in a subgroup of patients with smooth coronary arteries angina can be caused by an abnormality of the endothelial function in the microcirculation.