Lack of effects of trimetazidine on systemic hemodynamics in patients with coronary artery disease: a placebo-controlled study.

Trimetazidine has been shown to improve anginal symptoms and exercise tolerance in patients with coronary artery disease (CAD). To determine the hemodynamic effects of trimetazidine, systemic hemodynamics were studied in 15 patients suffering from CAD (12 male, 3 female, mean age +/- SEM = 58.6 +/- 1.8 years). Cardiac index was determined by thermodilution method. Left ventricular and aortic pressures were measured using micromanometers (Miller Instruments). After basal measurements, patients were randomly given either placebo (n = 5) or one of two therapeutic doses of trimetazidine 1 mg.kg-1 (n = 5) or trimetazidine 1.5 mg.kg-1 (n = 5) in a double-blind procedure. Data were recorded 5, 10 and 20 min after intravenous drug bolus. Throughout the procedure, the evolution of systemic hemodynamic parameters was not statistically different between the three groups, in particular heart rate, cardiac index, systolic, diastolic and mean aortic pressures, end-diastolic ventricular pressure, mean capillary wedge pressure, pulmonary artery pressures or systemic vascular resistances. We conclude that, unlike other antianginal drugs (particularly beta-blockers, nitrates and calcium-channel inhibitors), trimetazidine does not modify systemic hemodynamics in patients with CAD. These results are consistent with a direct effect of trimetazidine on the ischemic myocardial cell previously reported.

[Quantitative thallium myocardial tomoscintigraphy. Value of intravenous infusion of dipyridamole after negative submaximal exercise test]. / Tomoscintigraphie quantifiée au thallium. Intérêt d'une injection intraveineuse de dipyridamole après une épreuve d'effort sous maximale négative.

Patients with suspected coronary artery disease are sometimes unable to exercise adequately (85% of age calculated maximal heart rate) to validate their ergometric stress test. Some groups suggest performing dipyridamole scintigraphy from the outset but then the information provided by exercise stress testing is lost. The aim of this study was to compare scintigraphies performed after exercise alone and after exercise combined with dipyridamole using a method of quantification. Thirteen patients with ischaemic heart disease without necrosis (coronary lesions greater than 75% luminal narrowing in: 7 right coronary, 10 left anterior descending, 3 left circumflex arteries and 1 left main coronary artery with 50% luminal narrowing) underwent exercise stress testing followed by Thallium imaging. One week later, the same exercise stress test was performed followed by an intravenous injection of dipyridamole and Thallium scintigraphy. The circumference of the radioactivity was traced and the surface of each segment calculated in three different short axis views, subdivided into 4 segments (anterior, lateral, inferior and septal walls). Any segment vascularised by a stenosed coronary artery was considered to be underperfused (105 segments). The ratios of the surfaces of underperfused/normal segments were compared using the two study protocols. Segments of the same wall in the 3 short axis views were grouped in the same myocardial zone. Thirty five myocardial zones were thus obtained: 25 zones were more underperfused after combining exercise and dipyridamole than after simple exercise stress (p = 0.014). The average increase in underperfusion after the combined exercise-dipyridamole was 12.4% compared with 5.5% after exercise alone (p = 0.03). Secondary effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

[Demonstration of muscular activity in the human aorta. Effects of trinitrin]. / Mise en évidence d'une activité musculaire au niveau de l'aorte humaine. Effet de la trinitrine.

The human thoracic aorta is usually considered to be a purely elastic vessel. Transoesophageal echo-cardiography (TEE) provides a new approach to study the mechanical properties of the descending aorta. The aim of the study was to evaluate the reproducibility and accuracy of M mode recordings of the human descending thoracic aorta and to appreciate the changes produced by an infusion of glyceryl trinitrate (GTN). The reproducibility of M mode recordings was studied in vitro on plexiglass tubes of different calibre, and also in vivo, the inter and intra-observer error was estimated to 0.6% in vitro and 1% in vivo. The accuracy of the method was evaluated in vitro by comparing the measured values (MV) with the actual diameters of the plexiglass tubes (T): MV = 1.012T + 0.9; r = 0.99; SE = 0.8 mm. The systolic and diastolic diameters of the descending thoracic aorta were measured in 8 healthy volunteers by TEE, before and during continuous intravenous infusion of GTN at a rate of 0.9 mg/hr and then 1.35 mg/hr after a 10 minutes interval. Systolic and diastolic blood pressures were recorded automatically every minute. The results showed a very significant increase in the systolic (from 20.3 +/- 0.7 to 20.9 +/- 1.3 and 22.1 +/- 2.2 mm) and diastolic diameters of the aorta (from 18.3 +/- 0.7 to 19.1 +/- 1.4 and 20.1 +/- 2.4 mm) despite a fall in systolic blood pressure (from 121.3 +/- 7.7 to 114.5 +/- 6.6 and 108.4 +/- 5.4 mmHg). This study shows that TEE is a reliable and reproducible method of measuring the diameter of the human descending thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients.

To determine the incidence rate of complications associated with vascular catheters in intensive care unit patients and to analyze risk factors for a positive vascular culture, we performed a multicenter study of intensive care unit patients at eight French hospitals. During the study period, 865 intravenous catheters were inserted in 566 patients; 362 (41.8%) were peripheral catheters, and 503 (58.2%) were central catheters. Local complications (i.e., infiltration) occurred significantly more often with peripheral than with central catheters (P less than 0.001); in contrast, fever and bacteremia were significantly more often associated with central than with peripheral catheters (P less than 0.01 and P less than 0.05, respectively). The culture of the vascular-catheter tip was positive for 24% of central catheters (32 of 1,000 catheters days) and for 9% of peripheral catheters (21 of 1,000 catheters days). Staphylococcus epidermidis was the most common microorganism isolated from both peripheral and central catheters, followed by Staphylococcus aureus and Pseudomonas aeruginosa. No significant risk factor associated with positive cultures for peripheral catheters was found by univariate analysis. In contrast, the purpose of the cannula (nutrition and monitoring of central venous pressure), the insertion site (jugular), the dressing type (semipermeable transparent dressing), the antiseptic used to prepare the insertion site (povidone iodine), and routine changing of the intravenous administration set were significantly associated with positive cultures of central catheters. Three factors, duration of catheterization, use of a semipermeable transparent dressing, and the jugular insertion site, were found to be independently associated with positive cultures of central catheters by multivariate analysis.

[The value of recording the pulmonary insufficiency flow by continuous Doppler for the evaluation of systolic pulmonary artery pressure]. / Intérêt de l'enregistrement du flux d'insuffisance pulmonaire en doppler continu pour l'estimation de la pression artérielle pulmonaire systolique.

Systolic, diastolic and mean pulmonary artery pressures can be evaluated by Doppler recordings of the maximal velocity of tricuspid regurgitation and early and late diastolic pulmonary regurgitant flow. The aim of this study was to assess the reliability of the calculation of systolic pulmonary artery pressure from pulmonary regurgitant flow by comparing the values with those obtained from the tricuspid regurgitant flow in the same patient. With this objective in mind, we investigated 70 patients with an average age of 45 +/- 34 years, in sinus rhythm, all of whom had tricuspid and pulmonary regurgitant jets which could be recorded with continuous wave Doppler. Systolic pulmonary artery pressure was calculated as follows: from tricuspid regurgitation: maximum pressure gradient + 10 mmHg; from pulmonary regurgitation: 3 x early diastolic gradient - 2 x late diastolic gradient + 10 mmHg. The systolic pulmonary artery pressures calculated from tricuspid and pulmonary regurgitation were: 42 +/- 16 mmHg and 43 +/- 17 mmHg respectively (r = 0.97) with an estimated standard error of 4.7 mmHg. These results show that the recording of pulmonary regurgitation by continuous wave Doppler allows accurate estimation of pulmonary artery pressures. The calculation by the two methods using tricuspid and pulmonary regurgitant jets increases the reliability of the results and provides a means of internal validation of the Doppler technique.

[Enoximone in the hemodynamic evaluation before heart transplantation. A new test]. / L'énoximone dans le bilan hémodynamique prétransplantation cardiaque. Un nouveau test.

A better selection of patients referred for cardiac transplantation should lead to better surgical results. The presence of severe and irreversible pulmonary hypertension is an important factor and its pretransplantation assessment requires pharmacodynamic testing with vasodilators and dobutamine. The aim of this study of 10 patients in congestive cardiac failure referred for cardiac transplantation was to evaluate enoximone in this indication by comparing it with sodium nitroprussiate (3 micrograms/kg/mn). Intravenous enoximone (total dose of 1.5 mg/kg) increased the cardiac index (+49%; p less than 0.01), slightly reduced the mean systemic blood pressure (-8%; p less than 0.05) whilst inducing a greater reduction in systemic arterial resistances (-36%; p less than 0.01); the fall in mean blood pressure was less than with sodium nitroprussiate (-23%; p less than 0.01). Myocardial oxygen consumption (rate-pressure product) did not increase in contrast to the effect of dobutamine (+21%; p less than 0.01). There was a significant reduction in pulmonary arteriolar resistances (p less than 0.01) with all three drugs but the interpretation of this response and its prognostic significance in patients with a low cardiac output and persistent pulmonary hypertension are discutable even when pulmonary arteriolar resistances are less than 6 Wood units. The value of using an inotropic agent such as Dobutamine or Enoximone is to unmask fixed pulmonary hypertension which may be missed in patients with low cardiac output even with vasodilator drugs, and also to mimic the haemodynamic result of transplantation. In this indication Enoximone may be used like Dobutamine but with the advantage of not increasing myocardial oxygen consumption and being probably less arrhythmogenic.

Electrophysiologic effects of intravenous nicardipine on sinus node function and conduction in humans.

We conducted an intracardiac study of the electrophysiologic effects and kinetics of intravenous nicardipine (N) in 16 patients with or without impaired cardiac conduction, using a randomized, double-blind, crossover design versus placebo (P). N or P were infused intravenously over 5 min: the dose of N was 9.46 +/- 3.85 mg. Standard electrophysiologic parameters of atrioventricular (AV) conduction and sinus function were measured under basal conditions, between 10 and 25 min, and at 65 min, after beginning the first infusion of N or P, and between 10 and 25 min after beginning the second infusion of N or P. Treatment with N significantly reduced systolic (S) and diastolic (D) blood pressure (BP) at 10 min (35 +/- 19 and 25 +/- 17 mm Hg, respectively). N significantly shortened sinus cycle length (SCL), corrected sinus recovery time (CSNRT), AH interval, AV node (AVN) Wenckebach cycle length, and anterograde and retrograde effective (ERPs) and functional refractory periods (FRPs) of the AVN. Infranodal parameters were unaffected. Mean plasma N concentrations at 10 min were 18.5 +/- 7.7 ng/ml/kg and 5.3 +/- 3 ng/ml/kg at 60 min. Two patients experienced slight adverse effects (anginal pain and nausea); another with sick sinus syndrome developed a sinus pause. We conclude that intravenous N affects nodal, but not His conduction, and that it should be administered with care in the presence of SSS.

[Clinical application of echocardiography using a transesophageal approach]. / Applications cliniques de l'échocardiographie par voie transoesophagienne.

Transesophageal echocardiography is a new method of cardiac imaging with well-defined indications. In view of the absence of hindering anatomical obstacle between the probe and cardiac structures, the images obtained are of high definition, especially as regards the atria and atrial appendages, the mitral, aortic and tricuspid valves and the thoracic aorta. Being easy to perform and little traumatic, this method can be used in ambulatory patients. It is also valuable in intensive care patients and in the peri-operative period. Transesophageal echocardiography is primarily indicated to explore cardiac valve prostheses, notably those of the mitral valve, to identify vegetations and abscesses in infective endocarditis, to detect intra-atrial tumours and thrombi, to evaluate dissections of the aorta, to study the mechanism of mitral regurgitation, to investigate some congenital cardiopathies in adults, such as interatrial septal defects, and to monitor left ventricular function before and after surgery. Owing to its major contribution to the diagnosis of these potentially dangerous diseases, it should soon become a very useful and even indispensable complement of transthoracic exploration in certain cases.

Influence of training on blood lipids and coagulation.

Even if the effects of physical training on secondary prevention are controversial, it is known that exercise may influence several of the risk factors for coronary heart disease (CHD). One of the most important is cholesterol. Studies conducted to determine the influence of training on lipid profile have shown in normals, as well as in CHD patients, a favourable influence: a small decrease in total cholesterol and low-density lipoprotein cholesterol, and an increase in high-density lipoprotein cholesterol. These results are obtained after prolonged and intensive training. The influence of training on coagulation is more controversial and less well known. During short bouts of exercise the following changes are generally observed: an increase in platelet count and platelet aggregation (the effects on platelet adhesiveness and activation are controversial), potentiation of coagulation with an increase in factor VIII, and an increase in fibrinolytic activity due to an increase in plasminogen activator level. The effects of training have been less well studied. It is supposed that training could diminish the clotting potentiation observed during short exercise. Fibrinolysis is also increased in these conditions. If the influence of training on blood lipid profile may be considered as favourable in secondary prevention, no study has yet assessed the role of training on coagulation factors in secondary prevention.

[Short-axis thallium 201 tomography. Changes in the isotope fixation on the circumference of the left ventricle]. / Tomographie au thallium 201 en coupes petit axe. Etude de la variation de fixation de l'isotope sur la circonférence du ventricule gauche.

Several authors have studied variations in myocardial thickness on short-axis sections cut through healthy postmortem hearts. The circumferential profiles showed a series of minima and maxima, with a minimum at the septum, a maximum at the anterior interventricular junction and another at the anterolateral papillary muscle, a minimum at the inferior wall followed by a maximum at the posterior papillary muscle, then at the posterior interventricular junction, after which came a septal minimum again. When examined by short-axis thallium 201 tomography, the left ventricle does not look like a ring of even density. The purpose of this study was to try and explain the changes in density observed by variations in thickness and to devise a quantification method that would take anatomical features into account. 23 patients with normal coronary angiography underwent thallium 201 scanning after exercise. Circumferential profiles were drawn from short-axis sections with the angle on the abscissa and the number of sections on the ordinate. 29 other patients with a more than 75 p. 100 stenosis of coronary vessels (anterior interventricular artery 15, right coronary artery 10, circumflex artery 8, diagonal artery 4) had the same examination. The circumferential profiles of normal subjects closely resembled those of anatomical sections, with a minimum at the upper and anterior septal wall (the limit between the two areas being undefinable), a maximum at the anterolateral papillary muscle and adjacent myocardium, a minimum at the inferior wall and a maximum at the posterior papillary muscle and adjacent septum. These curves enabled us to determine the relative perfusion values of one area compared with another, which will serve as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

[Recurrent myocardial abscess during Streptococcus B endocarditis]. / Abcès myocardique récidivant au cours d'une endocardite à streptocoque B.

The authors report a case of serious streptococcus B endocarditis with a myocardial abscess that recurred after surgery. Streptococcus B endocarditis is a rare disease which is characterized by a pronounced tropism of the organism for cardiac tissues, with severe cardiac valve mutilation and abscess formation in 40% of the cases. A myocardial abscess makes the prognosis worse and must be treated surgically during the acute phase of endocarditis. Modern imaging methods, notably trans-oesophageal two-dimensional echocardiography and computerized tomography should now be used to detect such abscesses.

Prognostic significance of angina pectoris recurring soon after myocardial infarction.

The prognostic significance of an early occurrence, or recurrence, of angina pectoris after myocardial infarction was studied in 254 patients (221 male, 33 female; mean age 58 +/- 11 years). During the in-hospital rehabilitation program, 41 patients (16%) had anginal pain. The mean follow-up was 21 months (range 12-33 months). Among the 254 patients, 21 died, five had recurrent myocardial infarction, 13 had unstable angina, and 22 underwent aortocoronary bypass surgery. An early recurrence of angina pectoris was predictive of combined (medical + surgical) events (21 patients, P less than 0.05), medical events (11 patients, P less than 0.05) and surgical events (10 patients, P less than 0.001), but failed to predict individual death (six patients), recurrent myocardial infarction (two patients) or unstable angina (three patients). Of the events that occurred in the 254 patients, 34% were predicted by the early recurrence of angina pectoris. Early post-infarction angina was observed more frequently in older patients and patients with previous history of angina pectoris. This represents an important prognostic factor after myocardial infarction, which defines a high-risk group of patients requiring further investigation and appropriate therapeutic approaches.

[Prognostic value of the exercise test after myocardial infarction]. / Intérêt pronostique du test d'effort après infarctus du myocarde.

A stress test performed in the early stage after myocardial infarction enables to evaluate directly or indirectly three of the main prognosis factors: alteration of ventricular function, presence of ventricular arrhythmias, residual ischemia. This test, performed around the 15th day, after previous anti-angina treatment have been discontinued, is only done in the absence of the classic contra-indications. It permits to detect abnormalities: electrical positivity (with or without pain), disorder of the ventricular rhythm, abnormality of the blood pressure profile, low stress level. The predictive value of these abnormalities has been the subject of many studies. Although all the results are not in agreement, each one of these abnormalities seems to carry an increased risk of cardiac occurrences after myocardial infarction. In addition, an early stress test enables to detect pluritroncular coronary lesions with, however, an average sensitivity. Thallium scintigraphy in conjunction with a stress test improves, however, the performances of this test. The advantage of an early stress test is the rapid screening of high risk patients who should benefit from additional exploratory measures and possibly of myocardial revascularization procedures.

[Foreign body in the tricuspid valve with valvular insufficiency and right-left shunt]. / Corps étranger de la tricuspide avec insuffisance valvulaire et shunt droite-gauche.

We present the case of a 50-year old man who progressively developed tricuspid valve insufficiency with opening of a patent foramen ovale responsible for right-to-left shunt with polycythaemia. The tricuspid valve insufficiency was due to a foreign body, probably of surgical origin as suggested by its radiological image and by the patient's previous history. It would have been introduced, far away from the tricuspid valve (compound fracture of the wrist), several years previously. At surgery, we found the foreign body embedded in the valve system. As a possible mechanism for the mutilation, an undiagnosed endocarditis was suspected but could not be confirmed. Three cases tricuspid endocarditis (with foreign bodies in the right ventricle) and 3 cases of asymptomatic tricuspid valve foreign bodies have been published. Fifty-five cases of foreign bodies introduced peripherally and migrated into the heart, the pericardium and the pulmonary artery are reviewed.

Acute effects of trimetazidine evaluated by exercise testing.

A single dose of 60 mg trimetazidine (the normal daily dose) improved exercise capacity in angina pectoris, as reflected by an increase in the duration of exercise, total work performed, and improvement in ECG signs of ischaemia. All these effects occurred without any detectable chronotropic or vasomotor effect. The importance of this study is to demonstrate that these beneficial effects, already well-recognized after chronic administration of 20 mg three times a day, also occur after a single administration equivalent to the normal daily dose.

Quantification of aortic regurgitation using Doppler imaging.

Aortic insufficiency induces the development of a jet within the left ventricular outflow tract. The cross sectional area of this jet at its origin is the major determinant of the severity of the regurgitation. M mode Doppler imaging reportedly allows the measurement of jet diameter. This study was designed to evaluate the quantification of aortic regurgitation using a measurement of the jet diameter by M mode Doppler imaging. The left ventricular outflow tract of 32 patients was imaged using either a multigate pulsed Doppler velocimeter of color flow mapping system (Hewlett Packard). The jet diameter was compared to a 4 grade semiquantification derived from supravalvular aortography. Adequate imaging was obtained in the 32 patients. Four of them had no regurgitation: no diastolic flow image could be found during their Doppler investigation. A clear jet image was obtained in the 28 remaining patients. We found a close relationship between the jet diameter (jd in mm) and the angiographic grade (ag): jd = 2.4 + 6.1 ag, r = 0.88, the most significant differences being found between grade 0 and grade 1, and grade 1 and grade 2. In conclusion, direct M mode measurement of the regurgitant jet of aortic insufficiency at its origin offers an additional approach of the severity of the leak.

[Study of sinus function and nodal conduction using transesophageal recordings]. / Etude de la fonction sinusale et de la conduction nodale par voie transoesophagienne.

Transoesophageal pacing is mainly used for treatment of supraventricular tachycardias and assessment of refractory periods of accessory pathways. It has been proposed for the study of sinus node function and A-V nodal conduction. The aim of this study was to know if transoesophageal pacing could modify the vago-sympathetic tone, therefore the results of the tests, knowing it can be discomfortable and that endodigestive procedures can induce vagal responses. Furthermore, the stimulation is elicited near the left atrium, and not in the right atrium as during endocavitary tests. We have compared in 20 patients (age 68 +/- 12) the results obtained by both endocavitary and transoesophageal pacing (tension 21.2 +/- 4.5 V, duration 16 msec, interelectrode spacing 30 mm). We measured sino-atrial conduction time (SACT), sinus node recovery time (SNRT), Wenckebach's point and nodal refractory periods. After introduction of the oesophageal lead we observed a significant (p less than 0.01) but slight and transitory tachycardia. The results of A-V nodal conduction parameters were not significantly different and were significantly correlated (r = 0.94 for Wenckebach's point and effective refractory period). For the sinus node function, there was no significant difference between the parameters if the oesophago-atrial delay (mean 104.4 +/- 25.9 msec) is taken into account. The correlation is poor for sino-atrial conduction time (corrected SACT, r = 0.55), tighter for sinus node recovery time (maximal corrected SNRT, r = 0.92).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ergometric effects of a single administration of trimetazidine]. / Effets ergométriques d'une administration unique de trimétazidine.

The effects on exercise capacity of a single oral dose of 60 mg of trimetazidine were studied during a double-blind, placebo controlled cross-over study. Ten patients with stable angina and angiographically proven coronary artery lesions underwent ergometric bicycle exercise tests before and two hours after administration of the drug. A blood sample, for trimetazidine levels, was taken at the end of the recovery period. The homogeneity of the group and the lack of significance of the order of administration were established by cross-over analysis of the "control" tests and the "treated" tests. As compared with placebo, a statistically significant difference was noted after trimetazidine in the following parameters: total work (+31%, P less than 0.02), duration of exercise (+17%, P less than 0.02), percentage of the predicted maximal heart rate reached (+4%, P = 0.05), time to 1 mm ST segment depression (+17%, P less than 0.05) and degree of ST depression at maximum exercise level of the first control test (-31%, P less than 0.05); there was no significant difference in heart rate, blood pressure at rest and rate-pressure product during exercise between treatment and placebo. Two patients showed no response to trimetazidine. In the eight patients who did respond, there was a correlation factor of 0.73 between the plasma levels of trimetazidine and the increase in work performed. In conclusion, a single 60 mg dose of trimetazidine improves exercise tolerance and delays the ischaemic threshold during exercise without any detectable peripheral haemodynamic effects.