Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty.

OBJECTIVES: This study sought to determine whether pravastatin affects clinical or angiographic restenosis after coronary balloon angioplasty. BACKGROUND: Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. METHODS: In a multicenter, randomized, double-blind trial, 695 patients were randomized to receive pravastatin (40 mg/day) or placebo for 6 months after successful balloon angioplasty. All patients received aspirin (100 mg/day). The primary angiographic end point was minimal lumen diameter (MLD) at follow-up, assessed by quantitative coronary angiography. A sample size of 313 patients per group was required to demonstrate a difference of 0.13 mm in MLD between groups (allowing for a two-tailed alpha error of 0.05 and a beta error of 0.20). To allow for incomplete angiographic follow-up (estimated lost to follow-up rate of 10%), 690 randomized patients were required. Secondary end points were angiographic restenosis rate (restenosis assessed as a categoric variable, > 50% stenosis) and clinical events (death, myocardial infarction, target vessel revascularization). RESULTS: At baseline, clinical, demographic, angiographic and lipid variables did not differ significantly between groups. In patients treated with pravastatin, there was a significant reduction in total and low density lipoprotein cholesterol and triglyceride levels and a significant increase in high density lipoprotein cholesterol levels. At follow-up the MLD (mean +/- SD) was 1.47 +/- 0.62 mm in the placebo group and 1.54 +/- 0.66 mm in the pravastatin group (p = 0.21). Similarly, late loss and net gain did not differ significantly between groups. The restenosis rate (recurrence > 50% stenosis) was 43.8% in the placebo group and 39.2% in the pravastatin group (p = 0.26). Clinical restenosis did not differ significantly between groups. CONCLUSIONS: Although pravastatin has documented efficacy in reducing clinical events and angiographic disease progression in patients with coronary atherosclerosis, this study shows that it has no effect on angiographic outcome at the target site 6 months after coronary angioplasty.

[Prescriptions in cardiology]. / Comment je prescris aujourd'hui en cardiologie.

Prescriptions in cardiology have progressed from the often empirical and approximate approach used in the past to more rational approach based on the results of large clinical trials. For high blood pressure, bi- or even tri-therapy is often necessary. For coronary heart disease, betablockers, aspirin, calcium inhibitors, statins and converting enzyme inhibitors constitute the mainstay drugs. For myocardial infarction, the crucial point is to restore muyocardial perfusion as quickly as possible by thrombolysis or angioplasty. Polytherapy is required for heart failure. Finally, for atrial fibrillation, after anticoagulation, sinus rhythm can be restored with anticoagulant cover can be obtained with electrical shock or antiarrhythmic drugs.

Influence of SIN-1 on platelet Ca2+ handling in patients with suspected coronary artery disease: ex vivo and in vitro studies.

The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2-). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation. This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2- from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2- scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect. This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2- release, independently of H2O2 formation.

Relations of platelet Ca2+ handling and membrane microviscosity to vascular tone and restenosis after angioplasty in human coronary artery.

This study was designed to assess whether platelet Ca2+ handling or membrane microviscosity could be considered as indexes of vascular tone, or could help to predict an increased risk of restenosis after coronary angioplasty. Vascular tone was quantified in 21 patients with stable angina by the vasodilator response to sin-1 intracoronary injection in the reference coronary segment and by the importance of the acute recoil after angioplasty in the narrowed segment. The degree of restenosis was quantified by coronary angiography 6 months later. Individual values of relative sin-1-induced changes in the reference coronary diameter were positively correlated with cytosolic Ca2+ concentration in unstimulated platelets, irrespective of the extracellular Ca2+ concentration (p < 0.01). This relationship was also observed with the thrombin-evoked Ca2+ changes, measured in the absence of a Ca2+ influx (p = 0.01). No relationship was found between sin-1-induced coronary changes and membrane microviscosity evaluated by TMA-DPH and DPH anisotropies or platelet volume, or between degree of acute recoil and platelet characteristics. In conclusion, platelet Ca2+ reflects the vasodilating efficacy in response to sin-1, but cannot help to predict restenosis after coronary angioplasty.

Late coronary angioplasty and ventricular late potentials.

To assess the effect of successful late coronary angioplasty of an occluded infarct-related artery on the prevalence of ventricular late potentials, signal-averaged electrocardiograms were recorded in 123 consecutive patients surviving a first acute myocardial infarction (58 with and 65 without mechanical reperfusion of the occluded coronary artery). Multivariate analysis showed that successful reperfusion by late angioplasty of the infarct artery contributes to a decrease in the prevalence of late potentials.

Detection of coronary restenosis by exercise electrocardiography thallium-201 perfusion imaging and coronary angiography in asymptomatic patients after percutaneous transluminal coronary angioplasty.

Noninvasive detection of restenosis in patients remaining asymptomatic after percutaneous transluminal coronary angioplasty (PTCA) remains a major clinical problem. The value of exercise electrocardiography (ECG) and exercise-redistribution thallium-201 single-photon emission computed tomography (SPECT) in detecting restenosis in such patients remains uncertain. Discordances between these tests and coronary angiography is a common situation. We studied 179 consecutive patients remaining asymptomatic after successful PTCA (208 vessels), who underwent 6 +/- 2 months of exercise ECG, SPECT, and coronary angiography. We sought to assess the diagnostic value of the noninvasive tests compared with coronary angiography, and identify the determinants of discordances between the tests. Restenosis (diameter stenosis >50%) was detected in 39% of patients and in 37% of vessels. The overall sensitivity, specificity, and accuracy for exercise ECG and SPECT in detecting restenosis in individual vessels were, respectively, 53% versus 63% (p = 0.06), 59% versus 77% (p = 0.0001), and 57% versus 72% (p = 0. 0001). On multivariate analysis, positive exercise ECG was associated with higher heart rate response (p = 0.02), incomplete revascularization (p = 0.004), and angiographic restenosis (p = 0. 03), whereas positive SPECT was associated with incomplete revascularization (p = 0.02), infarct-related artery PTCA (p = 0.01), and angiographic restenosis (p = 0.0001). Accuracies of the 2 tests were not significantly different in patients with incomplete revascularization or PTCA of an infarct-related vessel. Overall, SPECT is more accurate than exercise ECG in detecting asymptomatic restenosis. Nevertheless, incomplete revascularization and PTCA of an infarct-related artery could cause reversible perfusion defects regardless of restenosis, reducing the diagnostic value of SPECT in such patients.

The effects of talking, reading, and silence on the "white coat" phenomenon in hypertensive patients.

To explore the mechanisms of the "white coat" phenomenon, the effects of talking, reading, and silence were analyzed. Fifty essential hypertensive patients were randomly allocated to periods of stress talking and relaxing reading, alternating with three periods of silence. While talking, systolic/diastolic blood pressure increased sharply, from 142 +/- 0.7/97.7 +/- 0.5 mm Hg to 159 +/- 0.7/111 +/- 0.5 mm Hg (P < .0001). While reading, systolic/diastolic blood pressure decreased (P < .0001). Moreover, talking and reading had opposite residual effects. The silence and reading periods gave the best approximations of the daytime ambulatory period. The predictive value of clinical blood pressure can be improved if measured during a period without talking, thus decreasing the "white coat" phenomenon.

The heparin management test: a new device for monitoring anticoagulation during coronary intervention.

Whole blood coagulation analysers are widely used during percutaneous coronary interventions. The precise degree of anticoagulation in patients is important in this setting. The aim of this investigation was to compare the results obtained with ACT (Hemochron) and HMT, the Heparin Management Test (TAS) in patients undergoing percutaneous coronary interventions. Patients (n = 100) were enrolled prospectively. Each patient received 10,000 units of heparin. At the end of the procedure, the mean ACT was 284+/-31 seconds and the mean HMT was 292+/-33 seconds. The correlation between the two methods was highly significant (r = 0.64, p<0.001). The HMT correlates well with ACT values in patients undergoing percutaneous coronary interventions. Its use in the management of these patients should be considered.

Relation between successful late coronary angioplasty of an occluded, infarction-related artery and lower prevalence of ventricular late potentials.

BACKGROUND: The effect of mechanical reperfusion of the infarction-related artery on ventricular late potentials (VLP) continues to be debated. OBJECTIVE: To assess the influence of successful late coronary angioplasty on the prevalence of VLP after acute myocardial infarction (AMI). METHODS: We studied 113 consecutive patients (97 men, 16 women, mean age 57 +/- 10.8 years) in whom the infarction-related artery was occluded (thrombolysis in myocardial infarction score 0 or 1) at the time of the initial coronary arteriography 10.9 +/- 6.4 days after a first AMI. Successful late angioplasty of the infarcted artery was performed in 55 patients a mean of 11.5 +/- 7.2 days after AMI. The remaining 58 patients received a conservative treatment. Signal-averaged electrocardiograms (SAECGs) were recorded 25 +/- 10.2 days after AMI. Multivariate analysis was undertaken to assess the influence of late coronary angioplasty with respect to age, sex, infarction site, angiographic ejection fraction, extent of diseased coronary arteries, thrombolysis and time of recording the SAECG. RESULTS: The overall prevalence of VLP was 27%. It was greater in patients without than in those with angioplasty (40% compared with 15%, P = 0.017). Multivariate analysis demonstrated that successful angioplasty (odds ratio 3.2; P = 0.019) and ejection fraction >0.4 (odds ratio 5.1; P = 0.0051) were the strongest independent predictors of an absence of VLP. 'Non-inferior' myocardial infarction was also correlated with the absence of VLP (odds ratio 2.6), but with borderline significance (P = 0.053). CONCLUSION: When performed in an occluded, infarction-related artery, successful late coronary angioplasty contributes to a significant decrease in the prevalence of VLP.

Arterial response to mild balloon injury in the normal rabbit: evidence for low proliferation rate in the adventitia.

BACKGROUND: The role of constrictive remodeling, spasm and proliferation (particularly in the adventitia) in the genesis of chronic lumen narrowing after balloon injury remains under debate. This study analyzed the time course of these components following mild injury in normal arteries. METHODS: Iliac injury was induced by balloon overstretch in 32 rabbits, sacrificed at timed intervals from day 3 to 28. Angiographic response to nitrates, morphometric, immunohistochemical and biochemical analysis were performed at each time point. RESULTS: Quantitative angiography showed a decrease in lumen diameter and no change in response to nitrates over time. On morphometric analysis, remodeling was usually constrictive, appeared as early as day 3 and was responsible for 69+/-14% of the histologic lumen area stenosis at day 28. Constrictive remodeling was correlated negatively to intimal hyperplasia (r= 0.51, P< 0.002) and positively to the lumen area stenosis (r= 0.92, P< 0.0001). Macrophages (labeled by anti-RAM 11 antibodies) were very rare at all time points. Immunohistochemistry identified a high rate of proliferating smooth muscle cells in the media (13+/-7%) and intima (49+/-8%) at day 7, which decreased rapidly. Proliferating cells in the adventitia were rare (3+/-2% at day 7). The number of proliferating cells was time-dependent (r= 0.82, P< 0.0001) and related to cyclin A mRNA measured by reverse transcription-polymerase chain reaction (r= 0.84, P< 0.0001). CONCLUSIONS: In this model, luminal loss was mainly caused by constrictive remodeling rather than intimal hyperplasia. Constrictive remodeling appeared early and was not time-dependent. Macrophages, spasm and adventitial proliferation did not contribute to this constrictive remodeling.

Cardiovascular reactivity to a new mental stress test: The maze test.

The response to the maze test was studied in 31 subjects on no medication, including seven subjects with mild essential hypertension. Beat-by-beat finger blood pressure (BP) was measured with a Finapres device. Pulse interval from which heart rate (HR) was derived was obtained from the BP signal. A period of 5 min baseline was used to define resting levels of systolic BP and HR using 20-s averaged values for the calculation of the 95% confidence limit of the two variables. The average test duration was 10 min. During this period a series of video-displayed mazes had to be solved with easy mazes preceding difficult ones. No subject had been exposed to the test before. The maximal BP elevation associated with the test was 27 mmHg. The HR response averaged 11 beats/min. Significant elevations were observed for half the test duration. No significant relationship between these two responses was observed and some subjects exhibited isolated systolic BP or HR responses. When indices obtained during this active mental stress were compared to resting values, positive correlations were observed. When the resting standard deviation (SD) of systolic BP was higher the systolic response was greater. A similar relationship was observed for HR. In addition, when the systolic BP level at rest was higher, the systolic BP reactivity index was greater. However, systolic BP or HR at baseline were not predictive of the systolic BP or HR responses. This study demonstrates the applicability of a new test to assess cardiovascular reactivity. The main advantage of non-invasive continuous BP measurement with the Finapres is the ability to provide variability indices in addition to the peak responses.

Usefulness of radionuclide ventriculography during transesophageal atrial pacing in the diagnosis of coronary artery disease.

Radionuclide ventriculography before, during, and after atrial transesophageal pacing was carried out in 15 patients with suspected coronary artery disease (CAD) and without myocardial infarction. All patients underwent coronary angiography. Ten patients (group 1) had a coronary lesion > 50% on at least one of the main coronary arteries. Five patients (group 2) had normal coronary arteries. Radionuclide left ventricular ejection fraction (LVEF) before pacing was 56 +/- 3% in group 1 and 59 +/- 3% in group 2 (NS). Radionuclide ventriculography during pacing was 45 +/- 4% in group 1 (P < 0.0001 vs basal in group 1) and 45 +/- 6% in group 2 (P < 0.01 vs basal in group 2, NS vs group 1 during pacing). Immediate postpacing ejection fraction did not differ in the two groups and was identical to the prepacing value. A quantitative regional wall motion analysis was performed in 105 segments. Regional radionuclide ventriculography was calculated in each segment as follows: end-diastolic counts-end-systolic counts/end-diastolic counts. The relative decrease in regional LVEF during pacing was more important in the 39 segments related to a narrowed vessel than in the 66 segments related to normal coronary artery (32 +/- 13% vs 13 +/- 10%, P < 0.0001). A more than 20% relative decrease in at least one segment during pacing occurred in 10 patients in group 1 (sensitivity 100%) and in 2 patients in group 2 (specificity 60%). In conclusion, global radionuclide ventriculography during transesophageal atrial pacing decreases in patients with and without CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Talking effect and "white coat" effect in hypertensive patients: physical effort or emotional content?

Talking has been shown to increase blood pressure instantaneously in hypertensive patients and to contribute to the white coat effect. The effects of talking were compared with those of counting aloud in 64 patients with essential hypertension who were randomly assigned to a period of stress talking and a period of counting aloud (active periods), alternating with three periods of silence (control). The same monitor was used for office measurements and 24-hour ambulatory blood pressure analysis. Systolic/diastolic blood pressures increased significantly more during talking (163/110 mmHg) than during counting aloud (152/102 mmHg, both p < .0001) in both treated and untreated patients and in sustained and clinical hypertension. Talking had a residual effect on systolic blood pressure that lasted 5.8 +/- 0.1 minutes. The emotional content seemed to be the only cause of the talking effect. Its instantaneous and residual effects on blood pressure and heart rate should be considered when measuring these variables.

Talking effect and white coat phenomenon in hypertensive patients.

Both white coat effect (the tendency of blood pressure to rise during a medical visit) and talking effect were analyzed in 42 patients with essential hypertension. Blood pressure was measured during the clinic visit and over the subsequent 24-hour ambulatory period, with the physician performing 49 +/- 4 measurements for each patient. Three silent periods and two talking periods (stress and relaxation) were randomly allocated in a crossover design and studied, using analysis of variance. During the initial 11-minute silent period, systolic/diastolic blood pressures increased by 6 mm Hg/5 mm Hg. During the subsequent talking periods, these variations were significantly greater: +22 mm Hg/+17 mm Hg. Measures of systolic/diastolic blood pressure were higher during stressful talking than during relaxed talking. The talking and its emotional contents seemed to explain 70% of the white coat phenomenon. To minimize the white coat phenomenon in the clinic, physicians, nurses, and clinicians are advised to measure blood pressure during an initial period of silence.

[Ethics and cardiology]. / Ethique et cardiologie.

The multiplication of therapeutic protocols and progressively more complex procedures, and the development of invasive procedures of interventional cardiology, have made ethics all the more important in cardiology. They should be prominent in the field of research where the primary objective is improvement of the health of the individual without abusing the dignity of the human person. The Huriet-Serusclat law of the December 20th 1988 was formulated in this spirit. However, ethics also intervene in clinical cardiological practice which should provide patients with the best treatment whilst avoiding technological excesses. Moreover, economical considerations constitute a true ethical challenge. Each individual should have access to quality health care without financial difficulties being an obstacle to this right. This equality necessitates a rational use of available resources and the taking into account of the collective interest. As an aid to decision and a barrier of protection, ethics imply constant reflection in order to supply patients with the best treatment without ignoring the interests of society.

[The classic anti-anginal agents and molsidomine]. / Les anti-angineux classiques et la molsidomine.

In the face of the recent introduction of beta-blockers and calcium inhibitors, the author examines the role of Amiodarone, Perhexiline and Molsidomine in the treatment of angina pectoris. Amiodarone, introduced in 1967, remains a very useful anti-anginal drug. The beta and alpha-sympathetic inhibition it produces, makes it effective in effort and resting angina. It is particularly useful in anginal patients with arrhythmias as it has a potent anti-arrhythmic effect at all levels. It can be used in patients with bronchial asthma, in elderly patients and in cardiac failure. However, it may give risk to hypo or hyperthyroidism and so, should not be used in patients with a history or thyroid disorders. Perhexiline has been used in France since 1973 and is a second-line drug to be used in cases of intolerance or contraindications to other anti-anginal drugs. It is effective but may cause severe, undesirable hepatic and neurological complications. These side effects are however rare at low doses. Molsidomine, a more recent molecule, has an action similar to that of the nitrate derivatives: it mainly reduces left ventricular preload. It has a slower onset of action than the classical nitrate derivatives but its duration of action seems to be longer; Molsidomine and betablockade can be a useful therapeutic association.

[Coronary bypass after thrombolysis]. / Le pontage coronaire après thrombolyse.

Owing to the development of transluminal angioplasty, coronary bypass surgery has now well-defined indications in patients who underwent thrombolysis. It may need to be performed in an emergency, but fortunately this only occurs in a few cases: in case of occlusion of the left main coronary vessel or equivalent lesions, when thrombolysis has failed and in case of failure of angioplasty with obliteration of large vessel and a still viable myocardium, and when the patient continues to suffer or shows signs of heart failure. The operative risk and the risk of haemorrhage then reach 10 p. 100. The installation, prior to surgery, of an intra-aortic counterpulsation system is useful in case of shock or left ventricular failure. Delayed coronary bypass is indicated mainly in case of three-vessel lesions with a less than 40 p. 100 ejection fraction, in case of stenosis of the left main coronary vessel or equivalent lesions, and in patients whose lesions are not amenable to angioplasty on a good caliber vessel, with a still viable myocardium. The operative risk in such cases is distinctly lower (2.4 p. 100). The long-term results obtained confirm the value of coronary bypass surgery when it becomes necessary after thrombolysis.

[Should inferior myocardial infarction be thrombolysed?]. / Faut-il thrombolyser les infarctus inférieurs?

Recent randomised studies have demonstrated the benefits of administration of intravenous thrombolytic agents in the acute phase of myocardial infarction. Though the benefits are generally acknowledged in cases of anterior wall necrosis, the results in inferior infarction have been discordant. The early patency rate at 90 minutes after thrombolysis is lower in the right coronary and left circumflex than in the left anterior descending artery. The secondary reocclusion rate is twice as high on the right coronary artery. The significant increase in ejection fraction after thrombolysis has only been demonstrated in 2 of the 8 studies in the literature. The benefits in terms of early mortality were not significant in the GISSI study. A significant decrease in early mortality (7.2% vs 8.8%) was observed only in the ISIS 2 study with streptokinase. The reinfarction rate at 1 year was twice as high when the initial infarct was on the inferior wall. Analysis of the results in the literature shows that the benefits of intravenous thrombolysis was clearcut in certain subgroups of inferior infarction: ST elevation in over 3 leads, mirror-image anterior lead changes, very early treatment (before the 3rd hour), complicated infarcts (atrioventricular block, right ventricular extension, hypotension) or in inferior infarcts occurring after previous anterior infarction.

[Thrombolysis after 75 years of age: benefits, risks, indications]. / La thrombolyse après 75 ans; bénéfices, risques, indications.

Hospital mortality of myocardial infarction in patients over 75 years of age ranges from 25 to 33% without thrombolysis. Large scale trials of intravenous thrombolytic therapy including elderly patients showed that age itself is not a contra-indication to thrombolytic therapy. However, on the one hand, contra-indications are more common, and, on the other, the characteristics of infarction in the elderly are unsuitable so that thrombolysis is rarely used: in the MITI study, only 15% of over 75 years old patients would have benefitted from this therapy. The benefits of this treatment in patients over 75 years of age have been demonstrated: they were significant in Collin's meta-analysis (hospital mortality 24.9 vs 28.8%). In a more recent analysis (FFT study) the benefits of thrombolytic therapy after 75 years of age were shown providing the delay of inclusion (< 6 hours) and classical electrocardiographic criteria (ST elevation) were respected. Moreover, age is a risk factor for cerebral haemorrhage (prevalence 2.08% in patients over 75 years of age in the GUSTO study). The results of this study showed that, despite the development of thrombolysis, age was the main risk factor for hospital mortality and was independent of other risk factors. Therefore, the indication of intravenous thrombolytic therapy in elderly patients should be considered with respect to the characteristics of infarction (delay, site, presence of subendocardial ischaemia), the contra-indication related to potential bleeding and the possibilities of performing emergency angioplasty.

[Holter monitoring and silent myocardial ischemia]. / Enregistrement de Holter et ischémie myocardique silencieuse.

Angina is not a very sensitive indicator of myocardial ischaemia. In patients with coronary disease 75 percent of ischaemic episodes are asymptomatic. Holter monitoring enables such silent episodes to be detected in daily life, this method becoming more sensitive when pursued for several days. The procedure is facilitated by a new generation of Holter recorders fitted with microprocessors that digitalize electrocardiograms. Silent episodes occur in the same circumstances as painful episodes, with a peak of incidence between 6 a.m. and noon, but they are often somewhat shorter. In patients with stable angina, as in those with unstable angina and after infarction, silent ischaemia is of poor prognosis. Holter monitoring therefore is useful in patients with known coronary disease to identify subjects at risk and to evaluate the effectiveness of anti-ischaemic treatments.