Use of bosentan for digital ulcers related to systemic sclerosis: a real-life retrospective French study of 89 patients treated since specific approval.

OBJECTIVES: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. METHOD: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. RESULTS: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. CONCLUSIONS: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

Vertebral fractures in Gaucher disease type I: data from the French "Observatoire" on Gaucher disease (FROG).

UNLABELLED: Gaucher disease type 1 (GD1), results in a range of skeletal complications including osteopenia, osteoporosis, and osteonecrosis, but there is little published information regarding vertebral fractures. Findings from this observational study indicated that the prevalence of vertebral fractures in a cohort of adult French GD1 patients is approximately 15%. INTRODUCTION: The aim of the study was to assess the prevalence and characteristics of vertebral fractures in a cohort of adult patients with GD1. METHODS: This study was performed in adult patients with GD1 based on a detailed and complete clinical examination. For all patients for whom vertebral fractures were reported, a specific questionnaire was sent to physicians, and imaging data were collected, when available, for centralized analysis. RESULTS: Data were collected from a total of 105 adult GD1 patients. Bone complications were reported in 85% of patients, among whom vertebral fractures were diagnosed in 16 (15%); seven women and nine men (mean age, 45 years). We observed five patients with multiple vertebral fractures and one patient in whom the T3 vertebra was fractured. Most of these patients did not report fracture-related back pain. CONCLUSIONS: The prevalence of vertebral fractures in this cohort of adult patients with GD1 was 15%. Greater awareness of the natural history of vertebral fractures in GD1, and rigorous monitoring of bone fragility and spine involvement in affected patients, should allow earlier detection and initiation of treatment tailored toward improving bone status.

Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.

Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis.

OBJECTIVES: There is increasing concern about heart and pulmonary vascular involvement in systemic sclerosis (SSc). One of the most severe complications of SSc is pulmonary arterial hypertension (PAH). There has been an increased awareness of left ventricular (LV) diastolic abnormalities in SSc patients. However, previous studies have generally been conducted in small populations. The aims of this study were to prospectively screen for PAH and to describe echocardiographic parameters in a large group of SSc patients. METHODS: This prospective study was conducted in 21 centres for SSc in France. Patients without severe pulmonary function abnormalities, severe cardiac disease and known PAH underwent Doppler echocardiography performed by a reference cardiologist. RESULTS: Of the 570 patients evaluated, PAH was suspected in 33 patients and was confirmed in 18 by right heart catheterisation. LV systolic dysfunction was rare (1.4%). LV hypertrophy was found in 22.6%, with LV diastolic dysfunction in 17.7%. These LV abnormalities were influenced by age, gender and blood pressure. We identified a small group of 21 patients with a restrictive mitral flow pattern in the absence of any other cardiopulmonary diseases, suggesting a specific cardiac involvement in SSc. CONCLUSIONS: Left and right heart diseases, including PAH, LV hypertrophy and diastolic dysfunction, are common in SSc. However, a small subset of patients without any cardiac or pulmonary diseases have a restrictive mitral flow pattern that could be due to primary cardiac involvement of SSc. The prognostic implications of the LV abnormalities will be evaluated in the 3-year follow-up of this cohort.

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects.

BACKGROUND: Bosentan is an effective first-line therapy in New York Heart Association (NYHA) III patients with idiopathic pulmonary arterial hypertension (PAH). Pre-clinical data support the rationale for the potential benefit of bosentan in PAH associated with congenital heart disease (CHD). MATERIALS AND METHODS: We performed a retrospective analysis of patients with PAH-associated CHD who were treated with bosentan on top of conventional therapy. Bosentan was started at 62.5 mg bid for 4 weeks, then titrated to 125 mg bid. New York Heart Association (NYHA) functional class, 6-min walking distance (6MWD), Borg dyspnoea index, arterial oxygen saturation and cardiopulmonary haemodynamic data (cardiac output, pulmonary blood flow and systemic and pulmonary vascular resistances) were collected at baseline and at follow up. RESULTS: Twenty-seven patients (23 females, mean 35 +/- 15 years) with NYHA class III-IV PAH-associated CHD (not repaired in 23 cases) were treated with bosentan for a mean 18.3 +/- 9.9 months. Bosentan improved 6MWD from 298 +/- 92 m at baseline to 355 +/- 82 m at 3 months (P = 0.0002) and to 364 +/- 92 m (P = 0.0001) at the last follow up (mean 15.2 +/- 9.7 months). At the last follow up, 13 patients had improved (= 1 NYHA class) and 14 remained stable. A favourable effect was observed in pulmonary blood flow and pulmonary vascular resistance for the 11 available patients. No change in pulse oximetry or liver enzyme elevation was reported. CONCLUSIONS: Bosentan improves exercise capacity, functional class and haemodynamics in most patients with PAH-associated CHD, without serious side-effects, suggesting bosentan may be an important treatment option for these patients.

[Pulmonary arterial hypertension in systemic sclerosis: definition of a screening algorithm for early detection (the ItinérAIR-Sclérodermie Study)]. / L'hypertension artérielle pulmonaire associée à la sclérodermie systémique: proposition d'un algorithme échocardiographique de dépistage pour un diagnostic précoce (ItinérAIR-Sclérodermie).

PURPOSE: Pulmonary arterial hypertension (PAH) is a severe complication of scleroderma. Its prevalence varies from 5% to 35% in the literature. A systematic yearly screening is recommended for early detection and management of PAH, but no precise algorithm is yet available. METHODS: From literature analysis as well as evaluation of medical needs and practices, a multidisciplinary board of experts proposed an algorithm for the screening of PAH in scleroderma. RESULTS: This algorithm is based on a precise Doppler echocardiography methodology for the purpose of screening scleroderma patients for PAH. Patients are considered as being at high or low risk of PAH depending on the maximal tricuspid regurgitation velocity. High-risk patients undergo right heart catheterization for confirmation of the diagnosis of PAH. A French multicenter transversal observational study ("ItinérAIR Sclérodermie") will be conducted in 21 hospital centers in France and involved 100 investigators organized as multidisciplinary networks. FUTURE PROSPECTS: Final results will provide confirmation that the screening algorithm is applicable in a real world setting, as well as a better knowledge of the prevalence of PAH in the various sub-groups of scleroderma patients, of the risk profile for PAH and of the value of DLCO as a predictive factor for PAH, and will support elaboration of precise screening guidelines.

Comparative effects of bisoprolol and nitrendipine on exercise capacity in hypertensive patients with regular physical activity.

The aim of this study was to evaluate the long-term effects of administering bisoprolol compared with nitrendipine on the duration of the exercise tolerated by male and female patients, aged 18-65 years, having mild to moderate hypertension and taking regular exercise. In this double-blind, randomized prospective study, 96 patients (85 men and 11 women, 48+/-10 years) formed two groups: 49 in the bisoprolol group, and 47 in the nitrendipine group. After a washout period of 14 days, either 10 mg of bisoprolol or 20 mg of nitrendipine was given daily over a treatment period of 12 weeks. During the treatment period, the stability of the physical training was monitored weekly by using a questionnaire. The results of two maximal triangular exercise tolerance tests (ETTs) on an ergometric bicycle performed at D0 under placebo and at D84 under active treatment were compared. No statistical difference was observed between both groups, concerning age, gender, morphologic characteristics, resting cardiovascular parameters, or physical training. Both groups maintained the same training level throughout the study. No significant differences between the groups were noted for duration of ETT [D0 892+/-284 s, D84, 919+/-267 s (NS) vs. D0 929+/-290 s, D84 904+/-324 s (NS)], or maximal work load [D0 190+/-49 W, D84 197+/-48 W (NS) vs. D0 198+/-49 W, D84 196+/-55 W (NS)]. On the other hand, both groups differed in maximal systolic blood pressure [D0 239+/-24 mm Hg, D84 215+/-22 mm Hg (p<0.001) vs. D0 237+/-24 mm Hg, D84 222+/-27 mm Hg (p<0.05)] (p = 0.05), and maximal pulse rate during exercise [141+/-18 vs. 163+/-17] (p<0.001), albeit not in maximal diastolic blood pressure [D0 113+/-13 mm Hg, D84 106+/-17 mm Hg (p<0.05) vs. D0 112+/-13 mm Hg, D84 104+/-15 mm Hg (p<0.05)]. The patient's own perception of the maximal effort (Borg scale) was not significantly different in either of the groups (placebo vs. treatment). Overall, in a population of hypertensive patients taking regular exercise, long-term treatment with bisoprolol produced no significant changes in the duration of peak effort, maximal workload, or the effort perceived by the patients themselves. The effects of regular exercise were comparable in both groups (bisoprolol or nitrendipine). Because previous studies have shown that dihydropyridines do not modify exercise performance in hypertensive patients, it may be concluded that the antihypertensive therapy with bisoprolol is well tolerated in a population of active hypertensive patients during dynamic exercise.

Comparison of bisoprolol and verapamil in hypertension: influence on left ventricular mass and function--a pilot study.

The objective of this study was to test the influence of bisoprolol and verapamil on left ventricular filling in hypertensive patients in a 6 month randomized, double-blind trial in 54 hypertensive patients not previously treated with beta-blockers or calcium inhibitors. After administration of placebo for 14 days, an M echocardiogram of the left ventricle was recorded to determine left ventricular mass. Blood flow was evaluated by pulsed Doppler sonography. After randomization into two groups, one group received 10 mg of bisoprolol and the other 240 mg of verapamil LP in a single dose in the morning. After 2 months' treatment, the patients whose blood pressure was not well controlled were given a diuretic. Echo-Doppler was performed again by the same operator after 4-10 days on active treatment, after 6 months and after a subsequent 2 weeks of placebo for the patients treated with a single drug. The reduction in blood pressure was comparable in the two treated groups, but there was no significant decrease in left ventricular mass. Left ventricular filling was improved only in the patients receiving bisoprolol. The effect was observed immediately after the first administration and throughout the 6 months' treatment period declining slowly during the placebo wash-out. This effect appeared to be independent of any alteration in heart rate and was thought to be a specific action of this drug.

Non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity.

AIM: The objective of this study was to evaluate the relationship between non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity in hypertensive patients. SUBJECTS AND METHODS: Ambulatory blood pressure measurements (15-min intervals for 24 h) and continuous blood pressure measurements (Finapres, 20 min at rest after a 10-min resting period) were performed in 123 untreated hypertensives (resting diastolic blood pressure > or = 90 mmHg; 80 males, 43 females; mean +/- SD age 49 +/- 12 years, range 19-73). Fourier series were used to model 24-h blood pressure profiles (four harmonics). Ambulatory blood pressure variability was assessed by determination of the residuals in each 24-h blood pressure profile (measured minus predicted pressures). Resting blood pressure variability was defined as the SD of the mean Finapres value. Baroreflex sensitivity was evaluated by automatic detection of blood pressure and pulse interval sequences of > or = 3 beats when systolic blood pressure and pulse interval sequences changed in the same direction (increase or decrease: 1 mmHg for systolic blood pressure and 4 ms for RR interval), and was assessed as the slope of the regression line for each sequence. RESULTS: Ambulatory systolic blood pressure variability increased with age (r = 0.28*) and systolic pressure (r = 0.44**). Baroreflex sensitivity (increasing systolic pressure/pulse interval) decreased significantly with age (r = -0.48**) and systolic pressure (r = -0.23**), and was significantly related to increased ambulatory blood pressure variability (r = -0.33**). In a multivariate stepwise analysis the relationship between ambulatory blood pressure variability and baroreflex sensitivity (increasing systolic pressure/pulse interval) was statistically independent of age and systolic pressure (R = 0.55, P<0.001); this relationship was not observed with the corresponding decreasing sequence. CONCLUSIONS: This study shows that in uncomplicated hypertension, ambulatory blood pressure variability is related to baroreflex sensitivity independently of the blood pressure level. This finding has prognostic implications for this non-invasive measurement, which needs to be confirmed by large longitudinal studies.

[Effects of bisoprolol and ramipril on short-term variability of systolic blood pressure during mental stress test: spectrum analysis]. / Effets du bisoprolol et du ramipril sur la variabilité à court terme de la pression artérielle au cours d'un test de stress mental: analyse spectrale.

UNLABELLED: The mid frequency component (MFC = 66-128 mHz) of blood pressure is an index of sympathetic vascular control. To investigate the effect of bisoprolol (B) and ramipril (R) treatment (TT) on the short-term variability of systolic blood pressure (SBP) diastolic blood pressure (DPB) and heart rate (HR) reactivity during mental stress, we studied 54 mild essential untreated hypertensive patients (24 men, 45 +/- 9.6 years, BP > 160/90 mmHg after a 15-days placebo run-in period) who were randomly assigned to double blind treatment (B: 10 mg/day: n = 28 and R: 5 mg/day: n = 26). A Stroop Word Color Conflict Test (SWCCT) was performed before and after 2 months of treatment. Hemodynamic parameters (BP and HR) were measured by a non invasive device (Finapres 2300E, Ohmeda-Maurepas) and underwent spectral analysis (SBP: mmHg.Hz-1/2, HR: beats/min.Hz-1/2, Anapres 1.2, Notocord-Orgametrie Systems, Igny-Lille) at rest and during SWCCT. The sympathetic vascular activity was assessed by calculating the area of the mid-frequency component (MFC = 66-128 Hz). RESULTS: [table: see text] CONCLUSION: The absolute variations in sympathetic activity during SWCCT as demonstrated by analysis of MFC of SBP and HR is not affected by chronic ramipril treatment, whereas bisoprolol attenuates sympathetic reactivity during SWCCT.

[Evaluation of lisinopril and lisinopril-hydrochlorothiazide combination in mild to moderate arterial hypertension]. / Evaluation du lisinopril et de l'association lisinopril-hydrochlorothiazide dans l'hypertension artérielle légère à modérée. Groupe de Travail Prinzide.

The main objective of this multicenter study was to compare the efficacy of an increase in dose and of a synergic combination in the 68 patients out of 126 (54%) with hypertension (DBP between 95 and 120 mm Hg after 2 weeks of placebo) who did not respond (DBP > or = 95 mmHg) to a 4-week treatment of 20 mg per day of lisinopril. Patients were randomized to receive a 4-week double-blind treatment of either 40 mg per day of lisinopril or the combination of 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide per day. Mean reductions of systolic (inter-group comparison: p = 0.08) and diastolic BP (p = 0.006) as well as the proportion of responders (82% versus 45%, p < or = 0.01) were greater with the lisinopril-hydrochlorothiazide combination than with 40 mg of lisinopril. Tolerance was good in the 3 groups. The administration of a synergic combination is justified when hypertension is not controlled by a monotherapy.

[Evaluation of the antihypertensive efficacy of lisinopril and captopril associated with hydrochlorothiazide by ambulatory measurement of arterial pressure]. / Evaluation de l'efficacité antihypertensive du lisinopril et du captopril associés à l'hydrochlorothiazide par mesure ambulatoire de la pression artérielle.

The objective of this study was to evaluate the efficacy, particularly in terms of the 24-hour cover, and the safety of lisinopril 20 mg + hydrochlorothiazide 12.5 mg 5L/HCTZ) and captopril 50 mg + hydrochlorothiazide 25 mg (C/HCTZ) in patients with essential HT requiring two-agent therapy. Twenty patients with a diastolic blood pressure (DBP) between 95 and 120 mmHg after 2 weeks of placebo were randomised to receive, under double-blind conditions, either L/HCTZ or C/HCTZ as a single daily dose for 4 weeks. Clinical examination, laboratory tests and 24-hour ambulatory blood pressure monitoring (ABPM) were performed at the end of the placebo and active treatment periods. L/HCTZ and C/HCTZ significantly lowered SBP and DBP on occasional recordings and on ABPM. The mean fall in blood pressure on ABPM (SBP, DBP, mean of 24-hour recording, diurnal and nocturnal) at 4 weeks was greater with L/HCTZ than with C/HCTZ. Both treatments were effective for 24 hours and did not alter the circadian cycle. The clinical and laboratory safety was good. The blood pressure figures obtained by ABPM were lower than on occasional recordings, emphasising the value of this technique in the evaluation of a patient's poor response to antihypertensive treatment.

[Is sudden reperfusion more arrhythmogenic during thrombolysis for myocardial infarction?]. / Une reperfusion plus soudaine est-elle plus arythmogène au cours de la thrombolyse pour infarctus du myocarde?

The object of this study was to analyse ventricular arrhythmias occurring during intravenous thrombolysis for acute myocardial infarction with respect to ST segment changes on 24 hour Holter ECG monitoring initiated at the same time as thrombolytic therapy and on repeated 12 lead electrocardiogrammes. Forty-one patients in whom the infarct-related artery was patent at coronary angiography carried out 30.5 +/- 3.1 hours (< or = 24 hours in 59% of cases) after the onset of chest pain were included. The time to normalisation of the ST segment was defined as the interval between maximum ST elevation to a steady state and helped identify rapid (< or = 60 minutes, n = 13) from intermediate (60-180 minutes, n = 15) and slow (> 180 minutes, n = 13) reperfusion. The incidence of ventricular arrhythmias was the same in all three groups, except for prolonged ventricular tachycardias (> 15 complexes): 69%, 13% and 15% respectively (p = 0.002). The number of arrhythmias was greater when the ST segment changes were rapid than when they were intermediate or slow. This was true for ventricular extrasystoles (p < 0.05), accelerated idioventricular rhythms (p < 0.05), early (< or = 6 hours from onset of thrombolysis) accelerated idioventricular rhythms (p < 0.01) and ventricular tachycardias (p < 0.05). Therefore, the number of ventricular arrhythmias seems to be related to the speed of ST segment change, suggesting that more sudden reperfusion is more arrhythmogenic.

[Evolution of the ST segment in myocardial reperfusion]. / Evolution du segment ST au cours de la reperfusion myocardique.

Intracoronary thrombolysis showed the chronological order of clinical electric and biological changes following the reestablishment of coronary flow. These changes make up the reperfusion syndrome; ST segment changes are part of this syndrome. They occur in practically all cases at the moment of reperfusion. The ST elevation may regress more or less rapidly or, on the contrary, increase transiently to a greater or lesser degree. When associated with other criteria of reperfusion-enzyme changes, arrhythmias, ST changes contribute to the indirect diagnosis of reestablishment of coronary flow. Rapid decrease in ST segment elevation is usually associated with a good myocardial outcome. The prognostic significance of transient increases in ST elevation--so called "reperfusion ischaemia"--is not fully understood, in particular its relationship to myocardial reperfusion injury. The myocardial prognosis after reperfusion may be the "biological" sum of cellular lesions due to ischaemia and reperfusion.

[Reperfusion arrhythmia]. / Arythmies de reperfusion.

Reperfusion arrhythmias were described from the first trials of intracoronary thrombolysis for myocardial infarction. The prevalence of ventricular fibrillation during intravenous thrombolysis is low (< 7%) and comparable to that observed with classical treatment. Holter recording shows that ventricular tachycardia and accelerated idioventricular rhythms occur in over 80% of cases. These arrhythmias are generally well tolerated and do not require specific therapy. A bradycardia-hypotension syndrome is observed in about a quarter of reperfused patients, nearly always in inferior wall infarction. It normally resolves spontaneously or after atropine or vascular filling. Reperfusion is associated with a clearcut increase in the number of episodes of arrhythmia. Some arrhythmias such as sustained ventricular tachycardia, early accelerated idioventricular rhythms (occurring in the first 6 hours) or the bradycardia-hypotension syndrome may be considered as non-invasive criteria of reperfusion. More severe ischemia and sudden reperfusion favour the arrhythmogenicity of reperfusion in the animal. Recent data suggest that this may be the case in the clinical context. In some uncontrolled studies, lidocaine, betablockers and aspirin did not affect the prevalence of the arrhythmias. Preliminary trials indicate that flunarizine and captopril may reduce the incidence of reperfusion arrhythmias in man. Ventricular arrhythmias and myocardial stunning could be the result of sa single phenomenon (the extent of the ischemic lesions or reperfusion lesions). Studies currently under way should clarify the relationship between the incidence of arrhythmias, the severity of stunning and myocardial recovery. Protocols evaluating therapeutic interventions on the reperfusate should include Holter monitoring.

Is arrhythmogenicity related to the speed of reperfusion during thrombolysis for myocardial infarction?

The objective of this study was to relate the number of ventricular arrhythmias (VA) to the normalization time of the ST segment during thrombolysis for acute myocardial infarction. The 24 h Holter recordings, begun on start of intravenous thrombolytic therapy, and the 12-lead electrocardiograms of 41 patients with a patent infarct-related artery according to coronary angiography were analysed. The mean time from onset of chest pain to angiography was 30.5 +/- 3.1 h, < or = 24 h in 59%. The normalization time of the ST segment, assessed by the time of decrease of ST segment elevation from start of Holter recording to normal or steady state was < or = 60 min in 13 patients (group 1), 60 to 180 min in 15 patients (group 2) and > 180 min in 13 patients (group 3). The incidence of VA was similar in all groups, except for ventricular tachycardias (VT) > 15 beats (group 1:69%, group 2:13%, group 3:15%, P = 0.002). The frequency of accelerated idioventricular rhythms (AIVR), early AIVR (< or = 6 h) and of VT was significantly higher in group 1 than in group 3 with a 8-, 30- and 6-fold increase, respectively (back transformed mean). We conclude that the number of VAs is related to the normalization time of the ST segment during reperfusion. This may suggest that faster reflow is more arrhythmogenic.

[Reperfusion-induced arrhythmia and oxidative stress]. / Arythmies de reperfusion et stress oxydant.

Although recognized and reproduced in numerous animal models, reperfusion arrhythmias were not studied extensively in humans until the advent of methods of coronary reperfusion during the acute phase of myocardial infarction. Usually of ventricular origin, these arrhythmias are polymorphic and constitute imperfect but useful markers of coronary reperfusion. Their electrophysiologic mechanisms are complex and their molecular mechanisms unelucidated. Predisposing conditions are the duration and severity of the ischemia, biochemical modifications such as heterogeneous uptake of extracellular potassium, magnesium deficit, intracellular calcium overload and release of arrhythmogenic lipid metabolites or prostaglandins. The autonomic nervous system also plays a part by an increase in the number and response of alpha-adrenoceptors. Furthermore, experimental studies provide theoretical and pharmacologic arguments for the participation of free oxygen radicals (superoxide anion (02.-, hydroxyl radical OH.) in reperfusion arrhythmias in the animal. By its complexity, human myocardial infarction differs markedly from the animal models studied; it probably involves, apart from the free oxygen radicals, multiple thrombotic, humoral and nervous factors whose respective role in the production of reperfusion arrhythmias remains to be established. Some enlightenment should be obtained by analysis of rhythmic events during proposed controlled studies using anti-free radical agents to prevent these post-myocardial infarct acute events.

[Holter monitoring of ventricular arrhythmia during the 24 first hours of myocardial infarction treated with intravenous thrombolysis]. / Enregistrement Holter des arythmies ventriculaires dans les 24 premières heures de l'infarctus du myocarde traité par thrombolyse intraveineuse.

The aim of this study was to assess ventricular arrhythmias after intravenous thrombolysis for acute myocardial infarction and to determine their relationship with coronary artery patency. A 24 hour Holter recording was started 3.1 +/- 0.2 hours after the onset of pain in 40 patients (age 54 +/- 1.6 years, 42.5% anterior infarcts) treated by streptokinase (42.5%) or tissue plasminogen activator (57.5%) within 3.3 +/- 0.2 hours of the beginning of symptoms. The arrhythmias were analysed on a Marquette 8000 computer. Coronary angiography was systematic and was performed 26.7 +/- 2.5 hours (within 4 hours in 60% of patients) after the onset of pain to define coronary artery patency (TIMI 2 and 3: 72.5%) or occlusion (TIMI 0 or 1: 27.5%). Ventricular arrhythmias were common and generally well tolerated (one defibrillation for ventricular fibrillation). Accelerated idioventricular rhythms and ventricular tachycardias were equally prevalent in patients with patent arteries (90% and 83%) as with occluded arteries (82% and 73%). The prevalence of sustained ventricular tachycardias (> 15 complexes) and of early accelerated idioventricular rhythms (< or = 6 hours) was significantly higher in patients with patent coronary arteries: 38% versus 0% (p < 0.05) and 76% versus 18% (p < 0.01). These arrhythmias may be considered to be non-invasive markers of early coronary reperfusion, with a sensitivity of 38 and 76% and a specificity of 100 and 82%. Coronary patency was associated with higher numbers of ventricular extrasystoles, ventricular tachycardias and accelerated idioventricular rhythms by a factor of 14, 13 and 32 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)