Genetic polymorphisms and coronary artery disease in the south of France.

Vascular disease is a multifactorial disease that involves atherosclerotic and thrombotic factors. Genetic polymorphisms have been associated with myocardial infarction and angina pectoris. The aim of the present study was to assess the relationship between some genetic polymorphisms and myocardial infarction (MI) or vasospastic angina pectoris in a population from southern France. Genetic polymorphisms of the renin angiotensin system (the D/I polymorphism of the ACE gene and the A1166C polymorphism of the angiotensin II type 1 receptor [AT1R]) and of haemostatic factors (the -675 4G/5G polymorphism of the plasminogen-activator inhibitor 1[PAI-1] gene, and the G to T common point mutation in exon 2, codon 34 of the Factor XIII A-subunit gene) were examined. We assessed the genotype distribution in consecutive coronary artery disease (CAD) patients with MI (n = 201) and vasospastic angina pectoris (n = 43) and in 244 healthy controls comparable in age, sex, body mass index and total cholesterol level. The genotype distribution of AT1R polymorphism was significantly different between controls and patients, the prevalence of the C allele carriers being higher in patients with MI after the age of 45 than in control individuals (61 vs 45%, p <0.01), leading to an odds ratio (OR) of 2 (CI: 1.2-3.4). When looking at the group of patients with vasospastic angina the difference was even higher (76 vs 45%, p <0.01) yielding an OR of 4.3 (CI: 1.4-17.4). Genotype distributions of ACE, PAI-1 and Factor XIII polymorphisms were similar in patients and in controls. This study is in favor of a role of ATIR gene polymorphism in myocardial infarction and vasospastic angina.

Fatal cerebral hemorrhage and severe thrombocytopenia during abciximab treatment.

We describe the case of a fatal cerebral hemorrhage associated with a severe thrombocytopenia (4.0 x 10(9)/l), occurring only 90 min after starting treatment with abciximab, in a patient undergoing primary percutaneous transluminal coronary angioplasty (PTCA) for an acute myocardial infarction. Cathet. Cardiovasc. Intervent. 49:177-180, 2000.

[Does diabetes change the anti-ischemic therapeutic options in the symptomatic coronary patient?]. / Le diabète modifie-t-il le choix des thérapeutiques anti-ischémiques chez le coronarien symptomatique?

The assessment of results of medical treatment, angioplasty and coronary bypass surgery in diabetic coronary patients is difficult because of the absence of distinction in the subgroups of type 1 and 2 diabetes and of stable and unstable angina. With respect to medical therapy, betablockers are practically without deleterious effects and are effective in diabetic populations. The same is true of other antianginal drugs. Conventional coronary angioplasty is associated with poorer results than the general population in the long-term, partly because of progression of the coronary artery disease and partly because of an increased incidence of restenosis. The use of stents improves these results, which are similar to those of the general population with single vessel disease or those without proteinuria. Coronary bypass surgery, despite a certain perioperative morbidity, is associated with an identical survival rate at 5 years as non-diabetics, providing the internal mammary artery is grafted. The comparison between these methods is resumed in the ACIP study which opposes the 3 strategies, in Morris et al's study comparing medical and surgical approaches and, finally, in the recent BARI trial where patients were randomly allocated to angioplasty or surgery. It would appear that the surgical strategy gives better results in multivessel disease. However, many reserves have been voiced because of the small numbers of patients, the high number of excluded patients and the fact that recent progress in angioplasty with widespread use of stenting associated with the prescription of new antiaggregant drugs was not taken into account.

[Acute complications of coronary angioplasty: prevention and management]. / Complications aiguës de l'angioplastie coronaire: prévention et prise en charge.

The immediate results of transluminal coronary angioplasty (TCA) have improved considerably during recent years. Balloon dilatation of the arterial stenosis is the basis of this technique of revascularisation but new tools may be used to treat specific lesions. Coronary occlusion is the most feared complication of TCA. It may cause myocardial infarction or death of the patient. It is usually secondary to dissection and/or thrombus of the artery. The implantation of a stent successfully treats most cases of dissection. New anti-platelet (GP IIb/IIIa) drugs seem to be very effective in the prevention and treatment of the thrombosis. The systematic use of ticlopidine limits the risk of stent occlusion. Improved features enable satisfactory implantation of stents in the majority of cases. In some patients, the clinical consequences of occlusion may be limited by vascular bypass techniques, especially intra-aortic balloon pumping. In other cases, emergency coronary bypass surgery may be necessary. When TCA is considered to be a very high risk procedure, effective surgical cover is essential.

Silent myocardial ischemia in patients with diabetes: who to screen.

OBJECTIVE: Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. RESULTS: Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. CONCLUSIONS: The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present.

Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells.

Circulating endothelial cells (CECs) have been detected in association with endothelial injury and therefore represent proof of serious damage to the vascular tree. Our aim was to investigate, using the technique of immunomagnetic separation, whether the pathological events in unstable angina (UA) or acute myocardial infarction (AMI) could cause desquamation of endothelial cells in circulating blood compared with effort angina (EA) and noncoronary chest pain. A high CEC count was found in AMI (median, 7.5 cells/mL; interquartile range, 4.1 to 43.5, P <.01 analysis of variance [ANOVA]) and UA (4.5; 0.75 to 13.25 cells/mL, P <.01) within 12 hours after chest pain as compared with controls (0; 0 to 0 cells/mL) and stable angina (0; 0 to 0 cells/mL). CEC levels in serial samples peaked at 15.5 (2.7 to 39) cells/mL 18 to 24 hours after AMI (P <.05 repeated measures ANOVA), but fell steadily after UA. Regardless of acute coronary events, the isolated cells displayed morphologic and immunologic features of vascular endothelium. The CECs were predominantly of macrovascular origin. They did not express the activation markers intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin, although some were positive for tissue factor. CECs failed to exhibit characteristics of apoptosis (TUNEL assay) excluding this event as a possible mechanism of cell detachment. The presence of CECs provides direct evidence of endothelial injury in AMI and UA, but not in stable angina, confirming that these diseases have different etiopathogenic mechanisms.

[Prospective study on the mechanism of myocardial infarction without significant coronary stenosis]. / Etude prospective sur le mécanisme de l'infarctus du myocarde sans sténose coronaire significative.

The aim of this study was to evaluate prospectively the respective roles of the atheromatous plaque, coronary spasm and abnormalities of haemostasis in patients with myocardial infarction with normal coronary arteries. The study population included 25 patients (19 men and 6 women) with a mean age of 52.1 +/- 11.1 years (34-76 years). The diagnosis of myocardial infarction was made as the finding of 2 out of 3 WHO criteria. It occurred spontaneously and was transmural in 80% of cases, inferior wall infarction in 9 patients (36%), anterior in 12 (48%) and lateral in 4 patients (16%). All patients underwent investigation on average 10 days after infarction (1-42 days) by coronary angiography with quantitative angiography, endocoronary ultrasonography, an ergometrine provocation test for coronary spasm and a blood coagulation study. Coronary angiography was normal in 4 patients but showed wall changes without stenosis > 50% in 20 patients and one case of aneurysmal arterial disease. Intracoronary thrombosis was detected in 6 cases. Endocoronary ultrasonography confirmed the normality of the coronary arteries in 2 cases and showed atheroma in 23 cases (soft atheroma: n = 17 and hard: n = 6). It detected 66% of the coronary thrombi observed at angiography and found 3 other cases. Coronary spasm was verified in 10 patients (40%). The coagulation study was normal in 19 patients and showed increase in Pai-1 in 5 patients and primary thrombocythemia in one case. The authors conclude that coronary angiographic data is less accurate than endo-coronary ultrasonography which best shows the extent and, above all, the nature of the plaques present in 23 of the cases (92%). Coronary spasm may be a contributing factor in 40% of cases, in situ thrombosis in 36% of cases despite usually normal blood clotting studies. None of these abnormalities was observed in one case. The embolic cause of infarction was certain in 2 cases.

[Detection and surveillance of left atrial thrombosis by transesophageal echocardiography]. / Détection et surveillance des caillots de l'oreillette gauche par échographie transoesophagienne.

Out of 1,141 successive transoesophageal echocardiographic studies performed prospectively between 01/05/1993 and 31/12/1995, 26 cases of left atrial thrombosis were observed (2.2%); 5 were in the left atrium (20%), 19 in the left atrial appendage (73%) and the thrombi were in both atrium and left atrial appendage in 2 cases (7%). The 26 patients included 15 women and 11 men, with an average age of 69 +/- 16 years (range 25-89 years); 22 patients (84%) had permanent atrial fibrillation and 4 were in sinus rhythm. Only 5 of the patients were on oral anticoagulant therapy. All had underlying cardiac disease: 11 mitral valve diseases; 10 dilated cardiomyopathies; 2 hypertrophic cardiomyopathies; 3 other cardiac diseases. The indication for transoesophageal echocardiography was systemic embolism in 13 cases (50%); before D.C. cardioversion in 10 cases (38%) and before percutaneous mitral valvuloplasty in 3 cases. The thrombus was adherent in 18 cases (69%) and mobile in 8 cases (31%). Spontaneous contrast was observed in 23 cases (88%). Intravenous heparin was given as soon as the diagnosis was made. In 4 patients, thrombectomy was indicated in view of the threatening nature of the thrombus and/or the necessity for associated valve replacement. In 22 patients, heparin was relayed by oral anticoagulants on the 10th day of treatment. Control transoesophageal echocardiography was not performed because of the patient's refusal or poor general condition. The other 15 patients were reexamined 1 to 5 times between the 4th day and 12th month: a regression was observed in 13 cases (86%) which was complete in 11 and partial in 2 cases. No cases of embolism occurred during follow-up but six patients died: 1 of the operated cases and 5 of the patients treated medically (3 cardiac failures and 2 cerebral haemorrhages). The authors conclude that left atrial thrombosis is rare in the absence of classical embolic cardiac disease. With the exception of the surgical indication of a life-threatening thrombus and/or associated surgical mitral valve disease, anticoagulant therapy results in complete or partial regression of the thrombus visualised by transoesophageal echocardiography which is essential for follow-up. The prognosis depends on the severity of the underlying heart disease.

[Frequency and nature of atheroma at the site of spasm of angiographically normal or subnormal coronary arteries: an endocoronary ultrasonographic study]. / Fréquence et nature de l'athérome sur le site vasospastique d'artères coronaires angiographiquement normales ou subnormales. Etude par échographie endocoronaire.

Anatomical studies suggest that sites of coronary spasm are subject to early atherosclerosis. Coronary angiography is unable to confirm the lesions or provide information about their nature. On the other hand, endocoronary ultrasound is able to identify and, it is hoped, to determine the frequency and composition of the lesions. Nineteen patients with chest pain and angiographically normal or subnormal coronary arteries were included in a prospective study (16 men and 3 women: average age 53 +/- 10 years). Four patients had spontaneous spasm and in the other 15, spasm was induced by intravenous injection of ergometrine (6 micrograms/kg). After countering the spasm with isosorbide dinitrate, the site of spasm and adjacent segments were examined by endocoronary ultrasound. Localised vasospasm which was stenotic in 14 cases and obstructive in 5 cases, was observed. The ECG was unchanged in 4 cases and showed ST-T segment changes in 15 cases. The artery affected was the left anterior descending in 10 cases, the left circumflex in 2 cases and the right coronary in 7 cases. A plaque of atheroma, defined as significant intimal thickening, was detected in 18 out of the 19 cases. This atheroma was classified as soft in 17 cases and hard in one case. The authors conclude that vasospasm is not only associated with a plaque of atheroma, nearly always suspected at coronary angiography, but also its composition is nearly always soft (lipidic) from ultrasonographic data.

[Heart rate variability and vagal syncope in the young adult]. / Variabilité sinusale et syncope vagale chez l'adulte jeune.

Heart rate variability is a sign of sympathetic activity. The authors compared two study populations of young males aged 19 to 30 years: population T comprised 15 healthy volunteers who had two negative tilt tests, one under basal conditions and the other after a bolus of isoproterenol; population S comprised 12 patients without cardiac or other disease, who were followed up for malaise and in whom the basal tilt test was positive, confirming the vagal origin of syncope. Temporal and spectral (total power, low frequency 0.04-0.15 Hz, hight frequency 0.16-0.40 Hz) data was obtained concerning heart rate variability from 24 hour Holter monitoring. The main difference between the two study populations was in the temporal data over 24 hours especially with respect to the heart rate (T = 73.5 +/- 6.9; S = 65.4 +/- 6.2/min; p = 0.004) and the percentage of successive R-R intervals varying by more than 50 ms (PNN 50) (T = 20.2 +/- 8.3%; S = 30.7 +/- 10.2%; p = 0.024). At night, the lowest SDANN/5 (standard deviation of RR intervals over periods of 5 minutes) were observed in group S (67.2 +/- 16.7 ms vs 87.3 +/- 24.4 ms; p = 0.026). No statistically significant differences between the two groups was observed in the spectral data. The temporal data of heart rate variability on Holter ECG monitoring over 24 hours could therefore have a good predictive value of the vagal origin of syncope in young adults.

Tilt table testing of young adult patients: improved speed and sensitivity using an isoproterenol bolus and a continuous 60 degrees tilt.

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 80 micrograms bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60 degrees tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 +/- 8.4 min) and 14 cases after administration of 5.1 +/- 1.9 micrograms of isoproterenol.

Clinical epidemiology of venous thromboembolic disease. Results of a French Multicentre Registry.

OBJECTIVE: Between July 1992 and December 1994, 16 French hospital centres, mainly cardiological, participated in a non-controlled observational study on venous thromboembolic disease. The objective of this survey was to collect data concerning the current status of pulmonary embolism and deep venous thrombosis. PATIENTS: During this period, 547 patients were included: 446 with deep venous thrombosis and 387 with pulmonary embolisms. RESULTS: Mean age of patients was 63 +/- 21 years. There were no significant differences between the sexes. Pulmonary embolism and deep venous thrombosis tended to occur more frequently during the autumn and winter. In 30% of cases, prior deep venous thrombosis or pulmonary embolism was noted. No cause was found for the condition in 47% of cases. Ultrasound (echocardiography and/or venous ultrasound) was the most frequently requested investigation. Intravenous heparin remains the most widely used treatment (76%). Oral anticoagulation was begun before day 3 in less than 31% of cases. Thrombolytic treatment was used in 20% of pulmonary embolism cases, but was rarely prescribed for deep venous thrombosis (2.2%). The hospital recurrence rate (12/547 cases) was fairly low. The search for occult malignancy, performed in 48% of cases, seems to remain one of the major concerns of physicians. The combined pulmonary embolism and deep venous thrombosis mortality rate was 4.4%, while the death rate for pulmonary embolism alone was 6.2%.

Clinical electrophysiologic effects of a single high oral dose of amiodarone.

Several recent reports have described the antiarrhythmic effects of a single high oral dose of amiodarone but clinical electrophysiologic effects have not been reported. The present study was performed to assess electrophysiologic effects in 12 patients. After baseline electrophysiologic studies (EPS) patients were administered a single oral dose of 30 mg/kg of amiodarone. EPS was repeated 7.5 +/- 0.5 hours later. Plasma levels of amiodarone and its metabolite desethylamiodarone were determined at the time of the second EPS, Holter monitoring was performed for 24 hours after amiodarone administration. Amiodarone significantly increased the following parameters: corrected QT interval (+4.5%), functional refractory period of the right atrium (+7%); AH interval (+12.3%), effective refractory period of the atrioventricular node (+18.5%), and cycle length of Wenckebach block (+8.4%). These effects were not correlated with plasma levels of amiodarone and desethylamiodarone. Holter monitoring detected no significant bradycardia or arrhythmia. These findings indicate that the effects of a single high oral dose of amiodarone are the same as those known to be induced by acute intravenous administration.

Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients.

Most studies on the natural course of coronary artery spasm in patients with normal or nearly normal coronary arteries are based on medium-term follow-up in small populations. The present series includes 277 successive patients with a median follow-up of 89 months (range: 1 to 198 months). There were 206 men and 71 women whose mean age was 53.6 +/- 9.3 years. They were all assessed with coronary arteriography which revealed no stenoses greater than 50%. Spasm was confirmed during the coronary arteriography in 157 patients (56.7%), by a positive provocation test following the arteriography in 113 patients (40.8%), and by an electrocardiogram which showed Prinzmetal's variant angina in seven patients (2.5%). The majority of patients, 264 (95.3%) were treated with calcium channel blockers. At the end of this study: 35 patients (12.6%) were lost to follow-up; 20 patients (7.2% died) including 10 (3.6%) from cardiac causes; 18 patients (6.5%) experienced myocardial infarction in 11 of whom repeat coronary arteriography consistently demonstrated one or more significant stenoses (greater than 70%); 109 patients (39%) had persistent angina, in 52 of whom the severity (more than one episode per month) warranted repeat coronary arteriography which detected significant stenosis in 19 cases; 95 patients (34.3%) were asymptomatic. Multivariate statistical analyses showed that only predictors of major coronary events (death, myocardial infarction or angina requiring repeat coronary arteriography) were systemic hypertension or the finding of minor parietal irregularities on the initial coronary arteriogram. Conclusion. Despite treatment with calcium channel blockers, persistent or recurrent episodes of angina are frequently observed whereas complications such as myocardial infarction or death are rare.

[Pulmonary arteriovenous fistula. A rare cause of dyspnea and cyanosis in an adult]. / Communication artério-veineuse pulmonaire. Une cause rare de dyspnée et de cyanose chez l'adulte.

The authors report the case of a pulmonary arteriovenous fistula presenting with dyspnoea and cyanosis in a young adult. The malformation was situated on the proximal pulmonary vessels and was cured by surgical correction. The diagnostic value of the clinical signs and complementary investigations of this rare conditions, often detected during adulthood, is discussed. The functional tolerance of the condition is often variable. Oxygen desaturation of arterial blood indicates a right-to-left shunt. Pulmonary angiography enables visualisation of the lesions and guides surgical management. The prevalence of complications of this condition is not well known, but the potential severity is an argument for therapeutic intervention. Embolisation techniques are developing but there is a risk of a systemic embolism. Surgery is the reference for the treatment of proximal fistulae, its curative effect being immediate and definitive.

[Spasm of normal or irregular coronary arteries. Long-term outcome of 277 patients]. / Spasme sur artères coronaires normales ou irrégulières. Devenir à long terme de 277 patients.

The outcome of patients presenting with spasm of normal or subnormal coronary arteries is only known in small series of patients at medium-term. The authors reviewed the outcome of 277 successive patients over an average period of 86 +/- 43 months (12 to 174 months). There were 206 men and 71 women with a mean age of 54 +/- 9 years. Coronary angiography was performed in all cases and did not show any stenosis greater than 50%. Spasm was documented during coronary angiography in 157 cases (57%) by a positive Methergin test after coronary angiography in 113 cases (41%) and by an ECG recording of Prinzmetal angina in 7 cases (2.5%). Nearly all patients (264: 95%) were treated by calcium antagonists. At the end of follow-up, there were: 35 lost to follow-up (12.6%), 20 deaths (7.2%) of which 10 were cardiac (3.6%), 18 myocardial infarctions (6.5%): 11 had repeat coronary angiography which showed one or more new significant (> 70%) coronary lesions in all cases; 109 patients had persistence of chest pain (39%). The severity of symptoms in 52 cases (over one attack of chest pain per month) led to repeat coronary angiography which showed significant coronary disease in 19 cases; 95 patients (34%) were asymptomatic. A multivariate statistical analysis showed hypertension or subnormal appearances on the initial coronary angiography to be significant predictive factors for new coronary events (death, myocardial infarction or angina requiring repeat coronary angiography). The authors conclude that coronary spasm of angiographically normal or subnormal arteries is only well controlled at long-term in 39% of patients not lost to follow-up and is responsible for death or myocardial infarction in 11.6% of cases (nearly 1.5% per year).

[Detection of circulating endothelial cells: a new diagnostic test of angina at rest]. / Détection des cellules endothéliales circulantes: un nouveau test diagnostique de l'angor de repos.

The diagnosis of spontaneous angina depends on the recording of per-critical electrocardiographic changes. There is no simple biological test to make its retrospective diagnosis. The attack is usually triggered by instability of an atheromatous plaque which fissures and liberates endothelial cells in the blod stream. The detection of these cells cold therefore be a biological sign of this condition. The technique of detection of circulating endothelial cells by immuno-magnetic method was used in 3 groups of patients admitted to hospital within 24 hours: group I comprised 11 patients with acute myocardial infarction, group II comprised 23 patients who had suffered from spontaneous angina with ST segment depression during the attack and significant coronary arterial stenosis, group III comprised 6 patients with chest pain for which coronary angiography is normal and provocative test of spasm is negative. Circulating endothelial cells were detected in all patients of group I (100%), in 18 of the 23 patients of group II (78%) and only in one of group III (18%). These results confer on this biological test for spontaneous angina a specificity and predictive positive value of 83 and 95% and a sensitivity and negative predictive value of 78 and 50%. Therefore the detection of circulating endothelial cells could be used as a simple and reliable test for retrospective diagnosis of spontaneous angina. The mediocre sensitivity and negative predictive value may be explained by a mechanism other than fissuration of atheromatous plaque in some cases of spontaneous angina.