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Resume Le secnidazole est un nouveau 5 nitro-imidazole possedant une activite antimicrobienne polyvalente, agissant a la fois comme antiparasitaire et antibacterien. Le secnidazole est employe dans les infections genitales a Trichomonas vaginalis, l’amibiase et la Giardiase. Le secnidazole possede une excellente activite sur les anaerobies, superposable a celle du metronidazole. Il est egalement actif sur des bacteries incurvees telles que Helicobacter pylori. Sur le plan pharmacocinetique, le secnidazole se caracterise par une demi-vie longue. Cela permet un traitement par dose unique de 2 g dans l’infection uro-genitale a Trichomonas vaginalis et la giardiase. Il en est de meme pour la vaginose bacterienne. La tolerance est bonne et liee a la prise unique de secnidazole.

A new apolipoprotein (apo) E variant, apoE5 (Glu212–>Lys) was identified in a Turkish family. The variant was due to a point mutation (CAG–>AAG) at the first nucleotide position of the codon encoding amino acid residue 212 of the mature apoE. The 23-year-old index patient was heterozygous for the mutation. Examination of the proband's kindred revealed six heterozygous and two homozygous mutation carriers. Compared to non-carriers, carriers of the mutation had slightly higher triglycerides (1.25 versus 1.11 g/l) and lower HDL cholesterol (0.36 versus 0.41 g/l). Very low density lipoproteins (VLDL) from an apoE5 (Glu212–>Lys) homozygote displayed enhanced binding (+17%, P < 0.05), but decreased uptake (-35%, P < 0.0001) and degradation (-51%, P < 0.0001) in cultured fibroblasts, compared to E3/3-VLDL. The region of the apoE molecule surrounding residue 212 contains a heparin binding domain. Consistently, the enhanced cell surface binding of E5/5-VLDL was observed in “wild-type” Chinese hamster ovary cells (+19%, P < 0.05), but not in proteoglycan-deficient cells. The binding of E5/5-VLDL to heparin was increased (+22%, P < 0.05). As the endocytosis of apoE-containing particles involves the transfer of proteoglycan-bound ligands to lipoprotein receptors, the stronger binding of apoE5 (Glu212–>Lys) to proteoglycans could reduce the rate at which the mutant is finally delivered to endocytotic pathways. These data may provide evidence for a functionally important heparin binding site around amino acid residue 212 of the apoE molecule in vivo.

The antibacterial activity of rufloxacin was confirmed against a large number of respiratory and urinary tract pathogens collected in five European countries. In terms of both MIC90 values and percentages of susceptible isolates found, this new quinolone showed useful in-vitro activity against Mycoplasma catarrhalis, Haemophilus influenzae and Klebsiella pneumoniae, with a large proportion of Staphylococcus aureus also covered, while, as expected Streptococcus pneumoniae and Streptococcus pyogenes were not included in its antibacterial spectrum. Rufloxacin was comparable with the other antibiotics against these pathogens with the exception of streptococci. Against these microorganisms, beta-lactams were the most active agents. Against the urinary pathogens the in-vitro activity of rufloxacin is similar to that of norfloxacin although this latter drug is more active in terms of MIC90 values and in percentages of strains inhibited. In many cases more isolates were susceptible to the remaining comparator agents than to rufloxacin. However, there were no significant differences between the numbers of microorganisms inhibited by the various drugs and rufloxacin. The findings of this survey do not seem to modify the general picture which emerged in previous studies and further confirms its useful spectrum in different geographic settings.

Optimal timing of surgery in infective endocarditis (IE) depends mainly on the haemodynamic tolerance of the patient. Emergency surgery is required in cases of refractory heart failure due to valvular lesions, intracardiac fistulas and high grade cardiac conduction abnormalities caused by septal abscesses. Surgery must be considered in all patients who have undergone a transient episode of heart failure such as a pulmonary oedema and it must be early--within 2 or 3 weeks of starting antibiotic therapy in patients with aortic regurgitation. Bacteriological indications are less frequent: persistent sepsis beyond the first week in spite of medical therapy, mycotic IE or prosthetic valve endocarditis caused by Gram-negative or staphylococcal organisms. Some complications may swing the argument in favour of surgery: detection of root abscesses or mycotic aneurysms using transoesophageal echocardiography, and systemic embolisms with persistent, large and mobile vegetative lesions. Mortality rate depends on the haemodynamic status but also on the severity of anatomical lesions, on the type of endocarditis (native or prosthetic valve), on the type of surgery and on bacterial aetiologies. It varies between 5% and 30%. The late postoperative outcome is good. The actuarial survival rate at 8 years was 70% in our series of 31 patients with aortic regurgitation and early surgery. In mitral regurgitation, conservative surgery is possible in most cases. In our department, 48 patients with mitral bacterial lesions have been operated on with conservative surgery without operative mortality. IE was active in 14, recent in 12 and had occurred earlier in 22.(ABSTRACT TRUNCATED AT 250 WORDS)

Although no epidemiological studies are available to evaluate the exact risk of infective endocarditis complicating native cardiac disease, analysis of data in the literature shows that cardiac disease can be classified into three groups of decreasing risk: (1) high risk disease includes cyanotic congenital heart lesions, previous bacterial endocarditis, aortic valve disease, mitral regurgitation and uncorrected left-to-right shunt, but not atrial septal defect; (2) cardiac conditions of moderate risk include mitral valve prolapse with valvar regurgitation or leaflet thickening, isolated mitral stenosis, tricuspid valve disease, pulmonary stenosis and hypertrophic cardiomyopathy; (3) conditions of low or no risk include isolated atrial septal defect, ischaemic heart disease and/or previous coronary artery bypass graft surgery, surgically corrected left-to-right shunt with no residual shunt, mitral valve prolapse with thin leaflets in the absence of regurgitation, and calcification of the mitral annulus.

A considerable amount of work has been devoted to thrombolytic therapy (about 3000 references from 1991 to 1995 in a Medline search). The most important and well established indication of thrombolytic treatment is acute myocardial infarction (MI). Megatrials have evidenced a significant 30 to 40% reduction in hospital mortality in the treated patients. However, lack of sufficient thrombolysis in approximately 25% of patients, reocclusion in 6 to 16% of patients and intracranial hemorrhage in about 0.5% of patients are the main concerns regarding thrombolysis. Three approaches should improve the results of thrombolytic therapy in acute MI: earlier medical treatment, use of more efficacious thrombolytic agents in combination with more active antithrombotic agents and reduction of severe bleeding with safer combination of drugs. An improved of laboratory monitoring may also reduce the incidence of severe hemorrhagic events. In acute pulmonary embolism (PE), a change of indication for treatment based on echocardiography and high probability ventilation-perfusion lung scan results (without requiring pulmonary angiography) could broaden the use of thrombolysis. However, thus far, there has not been a demonstration of a reduction in mortality in large controlled studies. Thrombolysis in acute ischemic stroke is an attractive treatment but thrombolytic treatment is still at an experimental stage. However, the successful use of rt-PA in acute MI has renewed the interest in thrombolysis for focal cerebro-vascular ischaemia. Large controlled studies with SK, rt-PA or UK locally or intravenously administered have been recently undertaken to evaluate the benefit/risk ratio of treatment which seems surprisingly variable in different subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Since 1984 and 1986. a new therapy has been proposed for patients with mitral and aortic stenosis. the Percutaneous Balloon Valvuloplasty (PBV). The outcome of the methods in each type of valvular heart disease have however been different. In mitral stenosis. PBV is used more frequently and the immediate and mid-term results are good when the technique is carried out by an experienced team. Percutaneous mitral valvuloplasty is, in many cases, the first therapeutic step and acts as a surgical commissurotomy. In aortic stenosis. PBV is rarely used because results are disappointing The procedure is however indicated in the elderly when the operative risk is prohibitively high.

Increased antimicrobial resistance in bacteria that are important pathogens of humans, and spread of resistance from the closed environment of hospitals into open communities are increasingly perceived as a threat to public health. Any antimicrobial use, whether in humans, animals, plants or food processing technology, could lead to bacterial resistance. Use of antimicrobials in livestock production is suspected to significantly contribute to this phenomenon in species of bacteria which are common to humans and animals. Further research is required into the specific use conditions that govern the selection and dissemination of resistant bacteria. International travel and trade in animals and food increase the risks of antimicrobial resistance world-wide. Countries are considering import restrictions for products deemed a risk to public health. The Office International des Epizooties, a World Trade Organization reference organisation for the Agreement on the Application of Sanitary and Phytosanitary Measures, develops international standards on antimicrobial resistance which, as is the case for national measures, must be based on risk analysis. The scientific background and problems of resistance in human medicine are reviewed. Current knowledge, missing information and actions to be taken are identified.

The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide. Resistance phenotypes of interest include multidrug-resistant pathogens, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and Streptococcus pneumoniae. Clusters of > or =2 isolates within a given resistance profile that are linked temporally and by hospital location are flagged for DNA fingerprinting. Further characterization of organisms with respect to resistance genotype is accomplished with use of polymerase chain reaction and DNA sequencing. This process has been highly successful in identifying clonal spread within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters identified by phenotypic screening contained evidence of clonal spread. Among the Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing clusters of infection, and approximately 50% of recognized clusters demonstrate clonal spread. Clusters of Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia have been noted with clonal spread among patients with urinary tract, respiratory, and bloodstream infections. Characterization of mutations in the FQR-determining region of phenotypically susceptible isolates of E. coli and S. pneumoniae has identified first-stage mutants among as many as 40% of isolates. The ability to characterize organisms phenotypically and genotypically is extremely powerful and provides unique information that is important in a global antimicrobial surveillance program.

The SENTRY Antimicrobial Surveillance Program was established to monitor the occurrence and antimicrobial susceptibility of bacterial pathogens via an international network of sentinel hospitals. Twenty European hospitals referred a total of 887 urinary tract infection (UTI) isolates to the European SENTRY reference laboratory during the period October-December 1997. Ninety percent of the referred species were represented by Escherichia coli (52%), Enterococcus spp. (12%), Klebsiella spp. (7%), Proteus spp. (7%), Pseudomonas aeruginosa (7%), and Enterobacter spp. (5%). The susceptibility of E. coli isolates to penicillins was less than 60%, while almost all of the isolates were susceptible to piperacillin/tazobactam (98% susceptibility), cephalosporins (98%), and carbapenems (100%). Amikacin was the best aminoglycoside (99.8% susceptibility). The susceptibility to quinolones was only 88-89%, with highest levels of resistance observed for isolates from Portugal, Italy, England, The Netherlands, and some centers in France, Spain, and Poland. The susceptibility of Klebsiella spp. to the newer generations of cephalosporins was 82-95% and to the carbapenems 100%. Amikacin was again the best aminoglycoside (94% susceptibility). The susceptibility of Enterobacter spp. to any beta-lactam antibiotic was poor, except for the carbapenems (100% susceptibility) and cefepime (90% susceptibility), while the susceptibility to aminoglycosides was 80-89%. Proteus spp. showed complete susceptibility to cefepime, ceftriaxone, the carbapenems, and piperacillin/tazobactam, while the susceptibility of P. aeruginosa isolates was poor, with best results for the carbapenems (susceptibility 89%), piperacillin/tazobactam (susceptibility 84%), and amikacin and ticarcillin (susceptibility to both 80%). Enterococcus spp. showed the highest susceptibility to vancomycin (98%), teicoplanin (98%), and ampicillin (94%).

The SENTRY antimicrobial surveillance program was established to monitor the occurrence and antimicrobial susceptibility of bacterial pathogens via an international network of sentinel hospitals.Microorganisms were forwarded to the reference laboratory for testing against various antimicrobial agents using broth microdilution. Twenty European hospitals referred 286 Streptococcus pneumoniae, 309 Haemophilus influenzae, and 167 Moraxella catarrhalis isolates during the first 10 months of the study, starting in April 1997.Seven percent of the S. pneumoniae isolates were highly resistant to penicillin, and 21% showed intermediate resistance. The highly resistant pneumococcal isolates came from Coimbra, Barcelona, Athens, and London, whereas the intermediate penicillin-resistant isolates were received from all participating countries. The incidence of intermediate penicillin-resistant pneumococci was lowest in Lausanne, Freiburg and Duesseldorf, London, and Utrecht and highest in southern European countries. Fifty-five percent of the penicillin-resistant S. pneumoniae were also resistant to erythromycin, and 35% to clindamycin. Sparfloxacin, trovafloxacin, levofloxacin, and vancomycin were fully active against pneumococcal isolates. Haemophilus influenzae isolates were generally highly susceptible to most of the antibiotics tested, and 92% of the M. catarrhalis isolates were resistant to penicillin. Susceptibility to cephalosporins, ciprofloxacin, levofloxacin, and rifampicin was 100%.Penicillin may no longer be the first-choice drug for empirical treatment of pneumococcal infections. The newer fluoroquinolones may play a role in the empirical treatment of community-acquired pneumonia.

The SENTRY Antimicrobial Surveillance Programme was established to provide a coordinated, standardised, international surveillance on antimicrobial resistance. In one part of the programme, isolates from skin and soft tissue infections sent from 20 hospitals in 12 different European countries were investigated in the European coordinating centre. Of 1013 isolates, Staphylococcus aureus and Pseudomonas aeruginosa were the most significant species, constituting almost 50% of the referred isolates. Methicillin resistance in Staphylococcus aureus averaged 22% across Europe, only slightly less than that in isolates derived from blood. Less than 5% of the enterococcal isolates were resistant to vancomycin. Piperacillin/tazobactam was the most active penicillin-derived beta-lactam compound against Pseudomonas aeruginosa, inhibiting 91.3% of the isolates, while ceftazidime and cefepime were the most active cephalosporins, inhibiting 85.8% and 80.3% of the isolates, respectively. Putative extended-spectrum beta-lactamase production was not detected in Escherichia coli and was found in only 5.1% of the Klebsiella pneumoniae isolates. In general, strains of the family Enterobacteriaceae remained mostly susceptible to carbapenems, cefepime, and amikacin.

To define the clinical, microbiological, and therapeutic characteristics of haemophilus endocarditis, we reviewed the charts of 42 adults with haemophilus endocarditis (native valve disease, 37; prosthetic valve disease, five) who were followed up between 1983 and 1995 in France. The mean duration of symptoms before diagnosis was 34 days. The causative Haemophilus species were as follows: H. parainfluenzae (26 adults), H. aphrophilus (9), H. paraphrophilus (4), and H. influenzae (3). According to the Duke criteria, 38 cases of endocarditis were definitive and four were possible. Thirty-nine patients received combination antibacterial therapy and three received therapy with a beta-lactam agent alone (mean duration, 46 days). Arterial embolism occurred in 15 patients. Cardiac surgery was indicated for 18 patients; 16 of these surgeries were performed within 3 months. Two patients died of heart failure. In conclusion, haemophilus endocarditis is rare and is mainly due to H. parainfluenzae. Although surgery is often necessary, haemophilus endocarditis has a favorable prognosis.

The antibiograms of 1162 bacterial strains, including references, have been performed within four centres. They have been read manually and by the SIRSCAN camera, which yields to 30936 couples of diameters values. A non-concordance, at a 3 mm level, was observed fot 11.14% of the diameters. The mean of difference is 0.82 mm and the standard deviation 3.34 mm. Round Petri dishes gave results less reliable than those obtained with square dishes. A deviation in function of the centres is obtained for wild-strains as for the references. For the whole population a S/R discordance (sensible/résistant confusion) is obtained for 1.76% of the diameters. This value drops to 0.93% for enterobacteriaceae, P. aeruginosa and S. aureus (968 strains).

A new apolipoprotein (apo) E variant, apoE5 (Glu212--Lys) was identified in a Turkish family. The variant was due to a point mutation (CAG--AAG) at the first nucleotide position of the codon encoding amino acid residue 212 of the mature apoE. The 23-year-old index patient was heterozygous for the mutation. Examination of the proband's kindred revealed six heterozygous and two homozygous mutation carriers. Compared to non-carriers, carriers of the mutation had slightly higher triglycerides (1.25 versus 1.11 g/l) and lower HDL cholesterol (0.36 versus 0.41 g/l). Very low density lipoproteins (VLDL) from an apoE5 (Glu212--Lys) homozygote displayed enhanced binding (+17%, P0.05), but decreased uptake (-35%, P0.0001) and degradation (-51%, P0.0001) in cultured fibroblasts, compared to E3/3-VLDL. The region of the apoE molecule surrounding residue 212 contains a heparin binding domain. Consistently, the enhanced cell surface binding of E5/5-VLDL was observed in "wild-type" Chinese hamster ovary cells (+19%, P0.05), but not in proteoglycan-deficient cells. The binding of E5/5-VLDL to heparin was increased (+22%, P0.05). As the endocytosis of apoE-containing particles involves the transfer of proteoglycan-bound ligands to lipoprotein receptors, the stronger binding of apoE5 (Glu212--Lys) to proteoglycans could reduce the rate at which the mutant is finally delivered to endocytotic pathways. These data may provide evidence for a functionally important heparin binding site around amino acid residue 212 of the apoE molecule in vivo.

The purpose of this study is to analyze treatment options for valvular regurgitation with severe left ventricular dysfunction.Results of valvular surgery in 98 patients with mitral or aortic regurgitation and severe systolic left ventricular dysfunction (LVD) were analyzed. Selection criteria were the absence of significant coronary heart disease and a resting ejection fraction (EF)40% for aortic and50% for mitral regurgitation.In patients with aortic regurgitation (n = 46) operative mortality was higher but not significantly so than in a control group of 238 cases (6.5% vs. 3.4%). The actuarial survival rates at five and 10 years were 84% and 55% vs. 84% and 67%, respectively. Independent preoperative predictors of severe postoperative LVD were rheumatic etiology and increased left ventricular end-systolic diameter. In patients with mitral regurgitation (n = 52), operative mortality was not significantly different from that of a control group of 273 cases (3.8% vs. 2.6%), whether the surgical procedure was valve replacement or valve repair. Perioperative morbidity was frequent (30% of cases), mainly low cardiac output, after valve replacement. The actuarial survival rates at eight years were respectively for the groups with and without LVD: 81% and 89% after valve repair, 60% and 75% after valve replacement. Independent predictors of severe postoperative LVD were increased left ventricular end-systolic volume and the type of surgery. Better results were observed after valve repair.It is concluded that a low EF is not a predictive factor of operative mortality but it influences late survival as do the degree of left ventricular dilatation, etiology in aortic and type of surgery in mitral regurgitation. Alternatives to valvular surgery have been envisaged but information on vasodilators in these patients is scant and results of heart transplantation are known only from a few small series.

Thromboembolic events are still a major cause of morbidity and mortality in patients with native valvular heart disease and in patients with prosthetic heart valves. Although the introduction of oral anticoagulation reduced this risk, thromboembolism and anticoagulation-related hemorrhages still represent significant problems in the management of these patients. In this article the guidelines developed by the Working Group on Valvular Heart Disease of the European Society of Cardiology for the management of antithrombotic therapy in heart valve disease are thoroughly discussed. The indication for and intensity of anticoagulation in various clinical situations, the concept of risk factor-adjusted intensity of anticoagulation, and the concept of control of oral anticoagulation with the International Normalized Ratio are presented.

This type of disease has benefited considerably, over recent decades, from progress in ultrasound technique and new methods of medical and surgical treatment. The aetiologies of mitral incompetence can be classified into 4 categories according to their mechanism: 1. Mutilating valve lesions, usually secondary to bacterial endocarditis, but sometimes secondary to trauma (percutaneous valvuloplasty). 2. Rupture of chordae tendineae, either spontaneous or bacterial, in a context of pre-existing valvular heart disease, usually degenerative. 3. Papillary muscle lesions, usually corresponding to rupture of a papillary muscle or the head of a papillary muscle, associated with myocardial infarction. 4. Biological or mechanical valve prosthesis dysfunction. The consequences of acute mitral incompetence depend on its aetiology and the presence or absence of previous mitral valve disease. Three factors determine the clinical presentation and prognosis: the volume of regurgitation, left ventricular function and left atrial compliance. In pure forms, such as those occurring after rupture of chordae tendineae, the haemodynamic profile consists of a marked elevation of left ventricular filling pressures, left atrial mean and systolic pressures (large V wave), and a reduction of the cardiac output. The left ventricular end-diastolic volume is moderately increased, while the end-systolic volume is normal or decreased and the ejection fraction is increased. The clinical picture is that of acute left ventricular failure with a systolic murmur of mitral regurgitation and a pulmonary hypertension syndrome. The absence of left ventricular hypertrophy on the electrocardiogram and the absence of left-sided dilatation on radiological examination indicate the recent nature of the haemodynamic disturbances. The diagnosis of acute IM is confirmed by Doppler ultrasound, which defines the mechanism and sometimes eliminates the need for an invasive investigation. The clinical course depends on the aetiology, the volume of regurgitation, left ventricular function and the treatment implemented. First-line treatment must include vasodilators. Sodium nitroprussate infusion decreases the left ventricular end-diastolic volume and the volume of regurgitation and increases the cardiac output. It allows a rapid reduction of pulmonary artery and capillary hypertension. When this treatment is not sufficient, intra-aortic counterpulsation may be useful. Emergency surgery is sometimes necessary, but usually after improvement of the haemodynamic state by vasodilators. Depending on the aetiology, surgery may consist of valve replacement or surgical repair, which can give excellent results even in the presence of active bacterial endocarditis. In other cases, following control of the acute phase by medical treatment, mitral incompetence will become chronic.

To identify the predictive factors of left ventricular dysfunction (LVD) after surgery, we performed an uni- and multivariate analysis of the data concerning 286 patients operated for pure aortic regurgitation between 1980 and 1994 and 460 patients operated for pure non-ischemic mitral regurgitation over a period of 24 years. Among the aortic regurgitation patients, 28 developed left ventricular dysfunction not attributable to residual aortic valve dysfunction, another valvular lesion or hypertensive or ischemic heart disease. By univariate analysis identified predictive factors of LVD were duration of symptoms prior to surgery, duration of the history of diastolic murmur, NYHA class, cardiothoracic ratio, LV echographic diameters, fractional shortening of short axis, LV end-systolic volume and LV ejection fraction. Multivariate analysis identified three independent predictors: NYHA functional class, LV end-systolic diameter and LV ejection fraction. Of 428 operative survivors with non-ischemic mitral regurgitation 63 developed severe LVD. Univariate analysis identified functional class III or IV, duration of symptoms prior to surgery, atrial fibrillation, echo LV and LA diameters, angio LV volumes, LV ejection fraction, cardiac index and type of surgery as independent predictors of LVD. Multivariate analysis showed that type of surgery, LV ejection fraction, LV end-diastolic and end-systolic volume and echo LV end-systolic diameter were all independent predictors of LVD.

Percutaneous mitral dilatation is now recognized as a valid alternative to open heart surgery. Indications have been clearly established for symptomatic patients with major stenosis (1.5 cm2, or 1 cm2/m2 body surface area). In other cases, the level of functional impairment, the anatomic state of the valve and the patient's past history must all be taken into consideration. In Western countries, there is a relatively large number of elderly patients with a moderately or severely damaged mitral valve. A critical evaluation of immediate and long-term outcome is required to determine the precise indications for dilatation and for surgery. Finally, these two methods should not be considered as contradictory but rather as complementary tools to control the natural history of the disease.

A French cooperative study of 155 pregnancies in 103 women with valvular prosthesis (95 mechanical, 60 bioprostheses including 27 bivalvular prostheses) is reported. Therefore, a total of 182 prostheses (108 mechanical and 74 bioprostheses) were exposed to the risk of pregnancy. The maternal outcome in the group of 108 mechanical prostheses was complicated by 16 thromboembolic events (TE) including 10 prosthetic valve thromboses which required emergency valve replacement in 4 cases, 6 systemic TE in 13 mitral, 2 aortic and 1 pulmonary mechanical prostheses. The TE were four times more frequent in patients on heparin than in those on oral anticoagulants. There were 4 deaths, 3 among the 10 prosthetic valve thromboses (one reoperation, two sudden deaths). Seven of the 74 bioprostheses were reoperated for degeneration on average 5.9 years after the initial operation but there were no deaths or TE. The outcome of pregnancy was 99 children (63%), 49 of which were born to mothers with mechanical prostheses (53%) and 50 to mothers with bioprostheses (80%) (p0.001). Seven of the children were born prematurely, all mothers being on anticoagulant therapy. The birth weight was over 400 grams heavier (3 kg versus 2.6 kg) in the bioprosthesis group (p0.05). The 20 spontaneous abortions (13%) were more common in patients on anticoagulants (17%) than in those without (2%) (p0.02). Congenital defects due to oral anticoagulants were rare (one certain case). There was one case of phocomelia, an abnormality which has never been described in this context. The 36 remaining pregnancies were still deaths (N = 5), abortion due to maternal death (N = 4), maternal complications (N = 8), therapeutic (N = 9) or voluntary abortions (N = 10) (28 mechanical and 8 bioprostheses).(ABSTRACT TRUNCATED AT 250 WORDS)

In order to analyse the results of conservative mitral valve surgery in the treatment of mitral regurgitation due to infective endocarditis, the authors reviewed the cases of 48 patients operated between 1974 and April 1993 (36 operations having been performed after 1989, a period during which only 3 patients underwent mitral valve replacement for the same indication). Thirty-four patients were operated after sterilisation of the infective endocarditis, and 14 patients were treated during the active phase. There were 32 men and 16 women with an average age of 45 +/- 13 years. In two thirds of the cases, the causative organism was a streptococcus. Half of the patients were operated during the acute stage because of their poor haemodynamic status, 5 because of residual bacterial vegetations after one or more embolic events and two because of the infection itself. On the other hand, patients were operated after the infective phase because of severe mitral regurgitation, responsible for severe symptoms (NYHA Class III) in 16 cases. From the anatomical point of view, the peroperative finding of 14 patients operated in the acute phase included dilatation of the annulus (N = 9), ruptured chordae (N = 9), perforation (N = 8) or vegetations (N = 8); in the patients operated later, the incidence of perforation and vegetations was much lower (20%) whereas dilatation of the annulus was almost constant (91%).(ABSTRACT TRUNCATED AT 250 WORDS)

This study was undertaken to determine the value of transoesophageal echocardiography in the follow-up of patients with severe mitral stenosis having undergone successful percutaneous mitral commissurotomy as defined as a final valve surface area1.5 cm2 without2/4 mitral regurgitation (MR). Eighty one patients who had undergone successful procedures were studied by transthoracic (TTE) and transoesophageal echocardiography (TOE) before, immediately after (24 to 48 hours) and at medium term (8 +/- 4 months) after balloon commissurotomy. The three main parameters studied were the degree of MR, presence of inter-atrial shunt and spontaneous left atrial contrast. Immediately after commissurotomy the MR was graded 0/4 in 6 patients (7.5%), 1/4 in 48 patients (59%) and 2/4 in 27 patients (33.5%). The TOE showed small traumatic lesions (localised valve tears, rupture of an accessory chordae tendinae) in 9 cases (11%). At medium term follow-up, the MR was stable in 75 patients (93%), decreased by one grade in 3 patients (3.5%), without the occurrence of severe MR. Interatrial shunts were more frequently observed by TOE than by TTE or oximetry with a prevalence of 57%. They usually disappeared at medium term follow-up. There were 3 factors associated with its persistence: a shunt visible at TTE, immediately after commissurotomy, visualisation of an atrial septal defect and a shunt jet widthor = 5 mm at TOE immediately after commissurotomy. Spontaneous contrast was common before the procedure (65%).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to determine the frequency, significance and prognosis of small, abnormal, strand-like echos observed by early transoesophageal echocardiography after mitral mechanical valve replacement with hemi-disc prostheses. One hundred and twenty nine consecutive patients operated between October 1988 and June 1992 underwent transoesophageal echocardiography on average 15 +/- 7 days after surgery. A second transoesophageal echocardiography was performed in 52 patients on average 8 months after the first postoperative examination. The frequency of small strand-like echos and of non-obstructive thromboses of the valve at the initial transoesophageal examination was 43% and 8.5% respectively. A multivariate analysis showed that the only independent predictive factor for prosthetic valve strands was spontaneous intra-atrial contrast (p0.01). The presence of strands was significantly related to the prevalence of early thrombo-embolic events (confirmed non-obstructive valve thrombosis and systemic embolism). Strands were observed in 80% of cases with early thromboembolic complications compared with only 38% of cases with no early thromboembolic events (p0.04). Univariate analysis showed that the protamine/heparin ratio at the end of cardiopulmonary bypass and the percentage of ineffective postoperative heparinisation were higher in patients with these small, abnormal echos (p0.05 and p0.001, respectively). These appearances disappear at long-term transoesophageal echocardiographic control examinations in about half the cases. The authors conclude that the majority of these small, abnormal echos are thrombotic in nature and are associated with a higher thromboembolic risk, justifying effective anticoagulation in the first postoperative hours whenever possible, considering the risk of bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Between January 1978 and June 1992, 798 patients underwent isolated AVR for hemodynamically significant calcific aortic stenosis. Preoperative coronary angiography was performed in 687 patients, of whom 229 had coronary stenosis40% and were divided into three (I, IIa and IIb) groups. Group I consisted of 144 patients undergoing AVR plus coronary artery bypass grafts (CABG); 39 patients in Group IIa had AVR only in the presence of coronary stenoses60%, and 46 patients in Group IIb had AVR only in the presence of coronary stenoses60%. Group III consisted of 144 matched patients selected from the remaining 458 patients with no coronary disease, or stenoses less than 40%, according to five matching criteria (age, sex, functional status, ejection fraction and year of surgery) with patients in Group I. Early mortality was 10.4% in Group I, 7.7% in Group IIa, 13% in Group IIb and 4.9% in Group III. Although the differences in operative mortality are apparent, they did not reach statistical significance. A difference in long term survival could only be detected between Groups I and III (actuarial survival at nine years 66% and 78.9%, respectively, p0.01). Similarly, late coronary events were more frequent in Group I than in Group III (13.9% vs. 5.1%, p0.03). It is concluded that revascularization should be as complete as possible for severe coronary stenoses coexisting with significant calcific aortic stenosis. However, bypassing of moderate coronary lesions (stenoses in the order of 50%) in association with AVR does not appear justified on current evidence. Further studies on this important aspect are clearly required.

This report analyses the efficacy and tolerance of percutaneous mitral commissurotomy (PMC) in 10 pregnant women with severe mitral stenosis. Pregnancy was the cause of decompensation of the mitral stenosis and surgery was not considered because of the foetal risk. PMC was undertaken after an average of 26 +/- 4 weeks of gestation (range 23-33 weeks). The average age of the patients was 28 +/- 6 years (range 20-41 years). Six patients were in NYHA Class III and 4 in Class IV despite medical treatment. Five patients had mild mitral regurgitation. Foetal protection was ensured by covering the mother's abdomen with a lead apron. The double balloon technique was used in 4 cases and Inoue's balloon in 6 patients. The average duration of fluoroscopy was 17 +/- 10 minutes (range 6-37 minutes). After PMC, the mean pulmonary artery pressure decreased from 47 +/- 12 mmHg to 31 +/- 11 mmHg (p = 0.005); two dimensional echocardiography showed an increase in mitral valve surface area from 1 +/- 0.2 cm2 to 2 +/- 0.3 cm2 (p = 0.005). There were no complications related to the procedure. The foetal heart rate was monitored continuously and no significant modification suggestive of foetal distress was recorded. The abdominal cutaneous dose of irradiation was less than 0.2 millisievert, which was minimal. All patients experienced a functional improvement after PMC. Nine delivered after an average gestation of 38 +/- 2 weeks (range 36-42 weeks) without cardiac decompensation. The average birth weight of the babies was 3.1 +/- 0.3 kg (range 2.9-3.7 kg).(ABSTRACT TRUNCATED AT 250 WORDS)

A 66 year old man with mild hypertension developed congestive cardiac failure of rapid onset associated with a continuous epigastric murmur suggesting an arteriovenous fistula. Doppler ultrasonography, computed tomography, magnetic resonance imaging and abdominal arteriography showed the fistula to arise from a large thrombosed aneurysm of the hepatic artery which had ruptured into the portal vein. Echocardiography and radionuclide angiography showed normal left ventricular systolic function. The patient underwent aneurysmorrhaphy and suture of the portal vein without any complications and the murmur and signs of cardiac failure disappeared. Histological examination showed the arterial lesion to be due to atherosclerosis. The authors underline the rarity of aneurysms of the hepatic artery and, above all, of their rupture into the portal system as there have only been 7 previously reported cases. Fistulae of the portal system are usually well tolerated, the commonest complication being portal hypertension. Cardiac failure is an exceptionally rare occurrence: it may be observed when the fistula develops suddenly and has a high flow rate, and in patients with abnormal myocardial function.

With the increasing age of patients and the progression of degenerative pathologies, the management of aortic stenosis (AS) with coronary artery disease is becoming more frequent. Reported results of combined valve and coronary surgery are equivocal especially with respect to the increased risk compared with aortic valve replacement without coronary surgery. The authors assessed the results of combined surgery by comparing two groups of patients with AS operated between 1979 and 1991: 122 patients with coronary lesions undergoing combined valve and coronary surgery (Group I) and 122 patients without coronary artery disease undergoing isolated aortic valve replacement (Group II) and paired with Group I patients for 5 prognostic factors (age, sex, functional status, date of surgery and left ventricular ejection fraction). Pairing the patients provided comparable populations for these 5 factors. The average age was high (68 years in Group I with over 50% of patients over 70 years of age) and most patients were in functional classes III or IV (67% in Group I). In Group I, 67% of patients had multivessel disease (average 2 vessel disease). Aortic valve replacement was associated with an average of 1.7 coronary bypass grafts per patient. Myocardial protection was the same in all cases using cold potassium enriched cardioplegic solutions. Operative mortality was 10.6% in Group I compared with 4.9% in Group II (NS) and the respective perioperative infarction rates were 6.6% and 0.8% (p0.02). Seven year actuarial survival rates were 71.8% in Group I and 74.9% in Group II (NS) without any increased late mortality in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to evaluate the incidence and prognostic value of ventricular arrhythmias in patients with aortic valve disease, 24 hour ambulatory electrocardiographic recordings were obtained in 374 patients without coronary artery disease (aortic stenosis n = 194, aortic regurgitation n = 103, combined aortic stenosis and regurgitation n = 77). Following aortic valve replacement, repeat recordings were obtained in a subgroup of 96 patients at 13 +/- 4 days and 18 +/- 7 months. Ventricular arrhythmias were classified in all cases according to Lown and were compared with clinical, echocardiographic and hemodynamic data. Preoperatively, ventricular premature beats were observed in 329 patients (88%), and were found to be frequent (30 ventricular premature beats/hour) in 83 (22%). Multiformity was found in 105 (28%), couplets in 75 (20%) and ventricular tachycardia in 45 (12%). The occurrence of ventricular arrhythmias was not related to the type or severity of the valve lesions. Patients with severe ventricular arrhythmias (Lown class 3 or 4: 36.5%) had a higher ventricular wall thickness (interventricular septum thickness 14.2 +/- 1.8 mm vs. 11.9 +/- 2.0 mm, p0.01, a higher LV mass (178 +/- 32 g/m2 vs. 142 +/- 35 g/m2, p0.001) and a lower left ventricular ejection fraction (48% +/- 9% vs. 56.5% +/- 10%, p0.001); while in patients with aortic regurgitation a higher end-diastolic LV volume (224 +/- 38 ml/m2 vs. 178 +/- 42 ml/m2, p0.02) and a higher end-systolic LV diameter (56 +/- 7 mm vs. 46 +/- 8 mm, p0.02) were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Since it was introduced, in 1984, as an alternative to surgical commissurotomy, percutaneous balloon mitral commissurotomy has been performed in a large number of patients with mitral valve stenosis, significantly improving the valvular function with a final area of 2 square centimetres. The quality of the result obtained basically depends on valve anatomy. The incidence of complications is globally low, with a mortality of 0.5 to 3 percent, and severe mitral regurgitation in 5 percent of the cases. Left-to-right atrial shunts are detected by oxymetry in 20 percent of the patients, but they subsequently vanish in two-thirds of them. For the moment, only medium-term results are available: when the initial result is good functional improvement is the rule, and the incidence of restenosis is low. Conversely, when the result is insufficient or severe mitral regurgitation develops secondary surgery is usually necessary. Before deciding to perform percutaneous commissurotomy, the contre-indications of this method (left atrial thrombosis, moderate to severe mitral insufficiency) must be excluded. In view of the encouraging results obtained, percutaneous commissurotomy can be advocated as first-line treatment of soft valve mitral stenosis. In patients with calcified valve mitral stenosis, valve replacement remains the principal treatment, percutaneous commissurotomy being reserved for special cases.

Thrombolytic therapy has been shown to preserve left ventricular function and reduce mortality in the acute phase of myocardial infarction. When the usual inclusion criteria are respected, only about 30% of patients can benefit from this form of treatment. The "excluded" cases are more numerous and have a worse prognosis. This has led to a review or the indications, especially with respect to age and the maximum time delay before instituting treatment. The data currently available comes mainly from large from retrospective analyses of subgroups taken from large scale thrombolytic trials, and must be confirmed by randomized studies specifically designed to analyse these problems. In elderly patients, the benefits in terms of mortality are important but the haemorrhagic risk is also greater and has to be accurately evaluated. Age by itself should not be considered to be an absolute contraindication to thrombolytic therapy which may be undertaken in elderly patients with large infarcts after having carefully excluded the other contraindications frequently observed in this age group. Late thrombolysis probably acts by mechanisms other than limitation of infarct size. The results are less impressive than when thrombolysis is instituted early require confirmation by the randomised studies currently under way. However, at present, is seems justified to prescribe thrombolytic therapy after the 6th hour in patients with large infarcts who continue to have chest pain. The limitations of thrombolytic therapy with regards to age and delay of administration should, therefore, be reconsidered taking into account the individual risk benefit ratio.

The aim of this study was to analyse the evolution of the aetiologies of operated valvular heart disease over a 20 year period and to assess the consequences. Two thousand five hundred and ninety eight patients who underwent conservative surgery or valve replacement were included. This population was classified according to the date of surgery into 4 groups, each corresponding to a 5 year period. Analysis of these results, especially in the groups operated between 1970 and 1974 and between 1985 and 1989 shows: 1) a change in aetiology: decreased incidence of rheumatic valvular disease (36 versus 61%) and an increased incidence of degenerative lesions (43 versus 23%) (p less than 0.0001); 2) a change in the valvular lesions operated, aortic stenosis has become the commonest operated condition (43 versus 27%) (less than 0.001); 3) an increased age (59 +/- 14 versus 49 +/- 13 years, p less than 0.0001) with a higher proportion of patients over 70 years of age (22 versus 1%, p less than 0.001); 4) a higher incidence of mixed coronary and valvular surgery (11 versus 2%, p less than 0.001).

Between 1969 and 1990, 75 adults living in mainland France underwent reoperation for bioprosthetic valve dysfunction. The average time between the initial operation and reoperation was 65 +/- 41 months. The average age was 44 years and half of the patients were severely symptomatic (NYHA Stages III or IV in half the cases). Dysfunction of an aortic valve prosthesis was observed in 65% of cases (N = 49) and of a mitral valve prosthesis in 35% of cases (N = 26). The causes of reoperation were: 50 primary degenerations (67%), 19 infectious endocarditis (25%) and 6 perivalvular leaks (8%). Valve replacement was performed in 74 cases and suture of the sewing ring in 1 case. An associated procedure was performed in 24 cases: 12 drainage of abscess, 10 double valve replacements and 2 tricuspid valvuloplasties. The operative mortality was 9.3% and early morbidity was 46%. Univariate and multivariate analysis identified two factors predictive of operative mortality: the duration of cardiopulmonary bypass and the cardiothoracic ratio. During follow-up, which lasted 36 +/- 31 months, there were 12 deaths, 4 of cardiac failure; 4 sudden deaths, 3 deaths related to the prosthesis and 1 extracardiac death. The 6 year actuarial survival rate was 71%. The cardiothoracic ratio, the preoperative ejection fraction and the bypass time were factors predictive of global showed bypass time and the cardiothoracic ratio to be prognostic factors. The 6 year survival without cardiac events was 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to evaluate the effect of aortic valve replacement on the incidence of ventricular arrhythmias in patients with aortic valve disease, 24-hour ambulatory electrocardiographic recordings were obtained before surgery in 96 patients without coronary artery disease (aortic stenosis n = 50, combined aortic stenosis and regurgitation n = 19 and aortic regurgitation n = 27). Following aortic valve replacement, repeat recordings were obtained after 13 +/- 4 days and 18 +/- 7 months. Ventricular arrhythmias were in all cases classified according to Lown and were compared with clinical, echocardiographic and hemodynamic data. Preoperatively, ventricular premature beats were observed in 85 patients (89%) and were frequent (greater than 30 ventricular premature beats/hour) in 20 (21%). Multiformity was found in 27 (28%), couplets in 18 (19%) and ventricular tachycardia in 11 (11.5%). The occurrence of ventricular arrhythmias was not related to the type or severity of valve lesions. Patients with severe ventricular arrhythmias (Lown class 3 or 4: 37%) had a greater thickness of their interventricular septum 13.9 +/- 2.5 mm, vs 11.7 +/- 2.6 (p less than 0.05); a higher LV mass 176 +/- 34 g/m2, vs 134 +/- 39 (p less than 0.05) and a lower left ventricular ejection fraction 47 +/- 12%, vs 57 +/- 11, (p less than 0.01). Two weeks postoperatively, the incidence and severity of ventricular arrhythmias had increased: ventricular premature beats were noted in 92% and were severe in 50%. No correlation was found between ventricular arrhythmias and preoperative or operative data. Eighteen months after surgery, ventricular premature beats were still observed in 81% of patients but remained frequent in 7% only. Severe ventricular arrhythmias were noted in 27%. Patients with severe ventricular arrhythmias had at the time of this late recording a lower radionuclide left ventricular ejection fraction 57 +/- 14%, vs 73 +/- 9 (p less than 0.02) and a higher enddiastolic diameter 63 +/- 15 mm, vs 48 +/- 7, (p less than 0.01). This study indicates that ventricular arrhythmias are common in patients with aortic valve disease. The severity of arrhythmias is influenced by the LV consequences of valve lesion both pre- and late postoperatively. The frequency and severity of ventricular arrhythmias increase early after surgery and do not correlate with preoperative or operative data.

The aim of this study was to assess the features of patients with severe mitral stenosis in relation to atrial rhythm. Six hundred and fifty patients (pts) with severe mitral stenosis (MS) (valve area less than or equal to 1.5 cm2) who underwent percutaneous balloon commissurotomy (n = 600) or surgery (n = 50) were classified into 3 groups according to their atrial rhythm (AR): group A: sinus rhythm (SR) (n = 379), group B: SR with episodes of transient atrial fibrillation (AF) (n = 65), group C: permanent AF (n = 206). Uni- and multivariate analysis of clinical, echocardiographic and hemodynamic parameters with respect to the atrial rhythm was performed. Some parameters were comparable in all 3 groups: sex, pulmonary, right and left atrial pressures, mitral valve area, incidence of associated aortic valve disease. Nine parameters were different: mean age, NYHA class III or IV, previous commissurotomy, previous embolism, cardiac index, mitral regurgitation, tricuspid regurgitation, left atrium diameter, mitral calcification. Multivariate analysis, identified age, left atrial diameter and presence of mitral calcification as independent predictors of atrial fibrillation. Transoesophageal echocardiography was performed in 167 cases. A spontaneous echo contrast was recorded in 106 cases (63.5%) and was significantly correlated with a history of embolism and or left atrial thrombi detected by echocardiography. Atrial fibrillation, size of left atrium, severity of mitral stenosis and cardiac index were found to be independent predictive factors of spontaneous echo contrast.

The choice of a valve replacement in patients over 70 years of age must take into account various parameters: the type of valve disorder being operated, the probability of post-operative survival in view of the stage of the valve disease and the age of the subject, and the advantages and draws-backs related to the replacements used. In the case of mechanical replacements, the main risks are related to the embolic and hemorrhagic problems inherent in anticoagulant treatment. In the case of biological replacements, the problems are related to the primary degeneration of these valves, which appears to be less frequent the higher the age. In patients over 75 years of age, bioreplacements have more advantages than mechanical valves. In subjects between 70 and 75 years of age, a mechanical valve can be recommended if there is no contraindication to anticoagulant treatment, if there is some other grounds for long-term anticoagulation and if the life expectancy appears to be greater than 10 years. In other situations, a bioreplacement is recommended.

This retrospective study assessed the prevalence of left atrial thrombi in mitral stenosis and evaluated the diagnostic value ot the main means of investigation Five hundred and eighty-one patients underwent open heart surgery over a 10 year period. The prevalence of atrial thrombi was 7%, the majority (60%) being located in the left atrial appendage. The sensitivity of transthoracic echocardiography for detecting thrombi in the left atrial cavity was satisfactory (65%) but was very poor for detecting thrombi in the left atrial appendage (4%). The results of invasive investigations (atrial angiography and coronary angiography) are no better. Without any doubt, transoesophageal echocardiography, performed in 101 patients in this series, has transformed these results (sensitivity 83%, specificity 97%). False negatives in this study mainly concerned small thrombi adherent to the atrial wall. Under these conditions, it would seem reasonable to propose transoesophageal echocardiography to all patients with mitral stenosis complicated by an embolic event or for those for whom percutaneous commissurotomy is suggested.

Medium-term results of valve replacement with a pericardial bioprosthesis were analysed in 141 patients receiving an Ionescu-Shiley aortic prosthesis and in 67 patients receiving a Mitroflow aortic (42), mitral (21) or double mitro-aortic (4) bioprostheses. There were 8 deaths in the operative (5.7%) and medium term (56 months) follow-up periods in the Ionescu group and a cumulative survival of 625 patient-years. There were 16 late deaths, 8 of cardiac origin. The 8 year survival and good functional results rates were 71% and 53% respectively. The linear rates of thrombo-embolism, endocarditis, reoperation, valvular dysfunction and regurgitation were 3.5, 1.1, 2.6, 2.7 and 6.1% patient-years. The corresponding figures in the Mitroflow bioprostheses were 0.5, 1.0, 3.1, 3.1 and 5.6% patient-years, but the average follow-up was shorter (36 months) with a cumulative survival of 195 patient-years. These results underline the frequency of primary valve dysfunction the mechanisms of which are: early tear in areas of high mechanical stress and late calcification. However, the hemodynamic profiles of this type of prosthesis are better than those of porcine bioprostheses which make them a valuable alternative in elderly patients operated for calcific aortic stenosis with a small aortic ring.