[Vitamin K in the neonate: Recommendations update]. / Vitamine K chez le nouveau-né : mise à jour des recommandations.

Hemorrhagic disease of the newborn is not common but may be very serious, with cerebral, hepatic, or adrenal gland bleeding. Its prevention is based upon vitamin K1 administration from birth. Scientific studies to validate appropriate treatment policies are scarce, with recommendations coming from expert opinions, retrospective studies, or controversies on possible side effects. After analysis of recent literature data, we propose an oral administration of three doses of 2mg of vitamin K1 at birth, at discharge from the maternity ward, and at 1 month postnatal age for term infants. For premature infants born with a birth weight above 1500g, a weekly dose of 2mg up to term equivalent age may be recommended. For premature infants below 1500g, a weekly dose of 1mg up to 1500g body weight, then a weekly dose of 2mg up to term equivalent age seems appropriate. If oral administration is not possible, the intravenous or intramuscular route may be used with a 50% reduction in dosing.

Predicting sudden death in the population: the Paris Prospective Study I.

BACKGROUND: Sudden death was found to share the same set of usual risk factors as coronary events and therefore could not be specifically predicted in the population. It appears, however, that parental history of sudden death has not been investigated yet as a risk factor for sudden death. Therefore, we assessed risk factors, including parental sudden death, associated with the occurrence of sudden death in a long-term cohort study. METHODS AND RESULTS: We included 7746 men employed by the city of Paris who were 43 to 52 years of age in 1967 to 1972 in the Paris Prospective Study I. Each subject underwent a physical examination and an ECG, provided blood for laboratory tests, and answered questionnaires administered by trained interviewers who paid particular attention to family medical history. Men with known ischemic cardiac disease were further excluded from analysis. For 95.5% of the men, vital status was obtained from specific inquiries until retirement, then by death certificates. Resting heart rate, systolic or diastolic blood pressure, tobacco consumption, body mass index, diabetes status, serum cholesterol, and parental history of sudden death were independent factors associated with sudden death during follow-up (23 years on average). When adjusted for confounding variables, including parental history of myocardial infarction, relative risk of sudden death associated with parental sudden death was 1.80 (95% CI, 1.11 to 2.88). CONCLUSIONS: Parental sudden death is an independent risk factor for sudden death in middle-aged men. The existence of familial risk factors for sudden death may help provide better identification of subjects at high risk of and early prevention of sudden death.

Endothelial dysfunction and collagen accumulation: two independent factors for restenosis and constrictive remodeling after experimental angioplasty.

BACKGROUND: Constrictive remodeling plays a prominent role in restenosis after balloon angioplasty, but its regulation remains unclear. Because endothelial dysfunction and changes in extracellular matrix have been reported after angioplasty, this study was designed to simultaneously evaluate endothelial function and collagen and elastin changes after restenosis and arterial remodeling. METHODS AND RESULTS: Atherosclerosis was induced in femoral arteries of 22 New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed. Histomorphometry and in vitro assessment of endothelial function were performed 4 weeks after angioplasty. Restenosis correlated with constrictive remodeling (r=0.60, P=0.01) but not with neointimal growth (r=-0.06, P=0.79). Restenosis correlated with an impaired relaxation to acetylcholine (ACh; r=0.61, P=0.02) but not with the response to the endothelium-independent vasodilator sodium nitroprusside (r=-0.25, P=0.40). Restenosis correlated positively with collagen accumulation (r=0.69, P=0.004) and inversely with elastin density (r=-0.48, P=0.05). Relaxations to ACh were significantly more decreased in arteries with constrictive remodeling than in those with enlargement remodeling (3.7+/-7.9% versus 35.5+/-15.0%, P=0.04). Neointimal collagen density was significantly higher in arteries with constrictive remodeling than in those with enlargement remodeling (34.5+/-4.5% versus 18.2+/-4.7%, P=0.03). Endothelial function and collagen and elastin density were independent predictors of restenosis in the study. CONCLUSIONS: These results demonstrate that the severity of restenosis after angioplasty correlated with both defective endothelium-dependent relaxation and increased collagen density.

"Crochetage" (notch) on R wave in inferior limb leads: a new independent electrocardiographic sign of atrial septal defect.

OBJECTIVES: This study sought to determine the clinical significance of a "crochetage" pattern--a notch near the apex of the R wave in electrocardiographic (ECG) inferior limb leads--in secundum atrial septal defect. BACKGROUND: Atrial septal defect is often overdiagnosed on the basis of classical clinical features. Thus, more specific signs on the ECG for screening are needed. Methods. We searched for a crochetage pattern in 1,560 older children and adults: 532 with secundum atrial septal defect, 266 with ventricular septal defect, 146 with pulmonary stenosis, 110 with mitral stenosis, 47 with cor pulmonale and 459 normal subjects. RESULTS: This pattern was observed respectively in 73.1%, 35.7%, 23.3%, 6.4%, 10.6% and 7.4% of these groups (p<0.001). In atrial septal defect, its incidence increased with larger anatomic defect (p<0.0001) or greater left-to-right shunt (p<0.0001), even in the presence of pulmonary hypertension. By multiple regression analysis, only shunt size (p<0.0006) and defect location (p<0.0001) were the determinants of its presence. In all groups, the specificity of this sign for the diagnosis was remarkably high when present in all three inferior limb leads (> or = to 92%), even when comparison was limited to patients with an incomplete right bundle branch block (> or = 95.2%). Early disappearance of this pattern was observed in 35.1% of the operated-on patients although the right bundle branch block pattern persisted. CONCLUSIONS: A crochetage pattern of the R wave in inferior limb leads is frequent in patients with atrial septal defect, correlates with shunt severity and is independent of the right bundle branch block pattern. Sensitivity and specificity of this sign are remarkably high when it is associated with an incomplete right bundle branch block or present in all inferior limb leads.

Resting heart rate as a predictive risk factor for sudden death in middle-aged men.

OBJECTIVE: A relative hyperadrenergic tone related to abnormalities of the autonomic nervous system is suspected in the mechanisms of sudden death. Therefore, we assessed the role of an elevated basal heart rate in the occurrence of sudden death in a long-term cohort study. METHODS: 7746 subjects aged 42--53 years, underwent ECG and physical examination conducted by a physician under standardized conditions, provided blood samples for laboratory tests, and answered questionnaires administered by trained interviewers. The vital status was obtained from specific inquiries up to the time of retirement and then by death certificates. Men with known ischemic heart disease were further excluded from analysis which was conducted on the 7079 remaining subjects. RESULTS: After an average follow-up period of 23 years, there were 2083 deaths, among which were 603 cardiovascular deaths including 118 sudden deaths and 192 following myocardial infarction. The crude risk of sudden death increased linearly with the level of resting heart rate and the risk in men in the highest quintile of heart rate was 3.8 fold than in those in the lowest quintile, whereas rates were approximatively twice higher for fatal myocardial infarction, cardiovascular and total mortality (all P<0.01). When age, body mass index, systolic blood pressure, tobacco consumption, parental history of myocardial infarction and parental history of sudden death, cholesterol level, diabetic status, and sport activity were simultaneously entered into the survival model, resting heart rate remained an independent risk factor for sudden death (P=0.03) but not for fatal myocardial infarction. CONCLUSION: An elevated heart rate at rest was confirmed as an independent risk factor for sudden death in middle-aged men.

Thrombus generation after adenovirus-mediated gene transfer into atherosclerotic arteries.

Thrombosis represents a major issue during arterial local delivery. We evaluated the occurrence of thrombosis after adenovirus (Ad)-mediated gene transfer into normal and atherosclerotic arteries. A replication-deficient Ad vector expressing the beta-galactosidase reporter gene (Ad.RSV betagal; 4 x 10(9) PFU) was injected into normal and atherosclerotic arteries (n = 11 in both groups). The contralateral artery received either an Ad vector carrying no transgene (Ad.MLPnull) (n = 7 in both groups, 4 x 10(9) PFU) or vehicle buffer (n = 4 in normal group, n = 8 in atherosclerotic group). Animals were sacrificed 3 days following gene transfer for thrombus detection and assessment of beta-galactosidase activity. Thrombus was absent in normal arteries and in atherosclerotic arteries injected with vehicle buffer only. In contrast, nonocclusive thrombus was present in atherosclerotic arteries injected with either Ad.RSV betagal (5 of 11) or Ad.MLPnull (3 of 7). Beta-galactosidase activity was predominantly found in the endothelial layer of the transfected arteries. Gene transfer and expression occurred despite the presence of the thrombus (4 of 5), and its efficiency did not significantly differ regardless of the thrombus. We conclude that thrombus frequently occurred in atherosclerotic arteries after Ad-mediated gene transfer. Further studies are warranted to identify the mechanisms of thrombus generation after Ad-mediated gene transfer into atherosclerotic arteries.

Pentosane polysulfate: the effect on hemostasis of a continuous 3-day infusion.

Pentosane polysulfate (PP) is a sulfated polysaccharide known to exhibit anticoagulant properties that are in part independent of antithrombin III activity. These effects have only been studied in vitro or after single injections in healthy subjects. Our objective was to evaluate the modification of hemostasis induced by a 3-day continuous infusion of PP (4 mg/kg body weight/24 hr) in 10 subjects. No hemorrhagic complication was observed in any patient. Bleeding time was not modified by the infusion, despite a slight decrease in the platelet number. Among the other parameters measured, the automated partial thromboplastin time, prothrombin time, and anti-Xa activity were the most affected by PP. The kinetics of their modifications were quite uniform: clotting times and the anti-Xa effect increased gradually until reaching steady state 24 hours after the start of the infusion. A progressive return to the pretreatment level was then observed during the 6 hours after the end of the infusion. A significant decrease in the factor V concentration was found at day 4. Finally, in contrast with other reported results, no activation of fibrinolysis was induced by PP under the conditions we used, which suggests that discontinuous administration or the route of administration of the drug influences the fibrinolytic effect. In conclusion, we show the excellent tolerance of continuous infusion of PP, detail the modifications in biologic parameters of hemostasis during and after PP infusion, and demonstrate that PP decreases factor V activity.

Intra-coronary thrombolysis with streptokinase or lys-plasminogen/urokinase in acute myocardial infarction: effects on recanalization and blood fibrinolysis.

Forty-two patients with total occlusion of a coronary vessel were treated with intracoronary fibrinolytic agents. Four therapeutic protocols were compared: group I received streptokinase (SK) as a continuous infusion; group II and III received SK as a bolus at different doses and group IV received lysplasminogen (Pg) plus urokinase (UK); maximal doses were 350,000 IU of SK and 250,000 IU of UK plus 75 microK of Pg. Thrombolysis was assessed by coronary angiography. Coagulation studies were performed prior to, 15 min and 6 hr after the end of the thrombolytic treatment. Recanalization was achieved in 27 of the 31 SK-treated patients (87%) and in 7 of the 11 Pg-UK-treated patients (63.6%). The recanalization frequency was the same in the three SK-treated groups, even though when SK was administered as a bolus, the dose was significantly less than when administered on a continuous infusion. Although systemic fibrinolysis occurred in all 4 groups of patients, this effect was less pronounced in the UK-treated patients than in the three SK-treated groups. This study also shows that recanalization can be achieved with a dose of SK lower than the anti-SK antibody level. Haemorrhagic side effects were minimal in all patients studied. Severe defibrination is usually considered a risk of haemorrhage. These preliminary results suggest that bolus injection of SK or the use of UK plus lys-Pg can reduce the level of defibrination and thus the haemorrhagic risk.

Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure.

STUDY OBJECTIVES: Respiratory muscle strength has been shown to be reduced in patients with chronic heart failure. The purpose of this prospective study was to determine whether long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor perindopril improves respiratory muscle strength in patients with chronic heart failure. PATIENTS AND METHODS: Eighteen patients with stable chronic heart failure were administered perindopril, 4 mg/d, in addition to their standard therapy for a period of 6 months. Fourteen patients completed the study. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) expressed in percentage of predicted values, left ventricular ejection fraction (LVEF) determined by means of two-dimensional echocardiography, and pulmonary volumes were obtained before and after therapy. MEASUREMENTS AND RESULTS: As compared to baseline, there was a significant increase in both PImax and PEmax after therapy (57 +/- 27% predicted vs 78 +/- 36% predicted and 62 +/- 20% predicted vs 73 +/- 15% predicted, respectively; each p < 0.05). LVEF increased (34 +/- 5% vs 41 +/- 10%; p < 0.05); functional class improved by > or = 1 New York Heart Association (NYHA) class in five patients. There were no changes in pulmonary volumes. No correlation was found between changes in PImax and PEmax and changes in either LVEF or NYHA functional class. CONCLUSIONS: In patients with chronic heart failure, long-term therapy with the ACE inhibitor perindopril improved respiratory muscle strength, as indicated by significant increases in PImax and PEmax.

Toxoplasma pericarditis in acquired immunodeficiency syndrome.

Large pericardial effusions are now a well-known complication of the acquired immunodeficiency syndrome, mainly caused by mycobacterial disease. However, other etiologies can be found. We report a case of toxoplasma pericarditis without other parasitic localizations. Pericarditis is a very uncommon clinical feature during toxoplasmosis. Its diagnosis is often difficult to establish, particularly in immunocompromised patients. Nevertheless, its possible evolution to constriction or tamponade requires its consideration. New methods of rapid tissue cultures may be helpful and allow early specific treatment.

Electrophysiological study of intravenous pinaverium bromide in cardiology.

Pinaverium bromide is a musculotropic spasmolytic agent which acts by inhibiting transmembrane calcium movements, an effect similar to that of verapamil. Because of this, an investigation was carried out to see if it had any electrophysiological effects in patients with various cardiac disorders. In an open study, 10 patients received 2 mg pinaverium bromide intravenously. In a double-blind study, 10 patients received 4 mg pinaverium bromide intravenously and 10 patients placebo. Patients included those with either normal or pathological basal conduction, such as bundle-branch block and 1st degree atrioventricular block. Measurements were made of electrophysiological parameters before and 10 minutes after injection. The results showed that neither of the two doses of pinaverium bromide had any effect on atrial excitability, sino-atrial conduction, node and trunk atrioventricular conduction or on intraventricular conduction. No significant difference was seen in comparison with placebo. Pinaverium bromide had no anti-arrhythmic properties in these studies. Local, cardiac and general clinical tolerability was good in all patients.

Investigation of drug interactions with pinaverium bromide.

A series of studies was carried out at 6 centres to investigate possible drug interaction between the spasmolytic, pinaverium bromide, and cardiac glycosides, anticoagulants and hypoglycaemic agents given to patients as part of the long-term treatment of their condition. The results of clinical and laboratory investigations did not show any evidence of pinaverium bromide interfering with the action or activity of any of the drugs studied.

[What is left of invasive electrophysiological explorations?]. / Que reste-t-il des explorations électrophysiologiques invasives?

After a golden period during which invasive electrophysiological investigations improved our understanding of the physiopathology of cardiac arrhythmias the clinical indications have now become more restricted. In the investigation of syncope, electrophysiological studies are only envisaged when the diagnosis is uncertain after clinical examination, resting ECG and non-invasive investigations. Holter monitoring in particular. Three types of arrhythmia may confirm our positive diagnostic criteria: sinoatrial block in patients with a sinus node recovery time greater than 1,000 ms uninfluenced by atropine atrioventricular block in patients with distal conduction defects during sustained atrial pacing, if necessary after injection of ajmaline: ventricular tachycardia in patients sustained monomorphic VT induced by 2 or 3 extrastimuli. The selection of the clinical indications has significantly improved the diagnostic value of electrophysiological investigations. The negativity of a strictly performed protocol, even though not giving a precise diagnosis of a syncopal episode, does provide reassuring prognostic information. In VT, electrophysiological studies may also be used to evaluate the secondary prognosis but with a diagnostic value no greater than that of non-invasive investigations. Programmed ventricular stimulation is not systematic for guiding antiarrhythmic therapy in France. Reserved for recurrent VT, electrophysiological studies are of additional value in the adaptation of treatment and improve the secondary prognosis.

[Myocardial bridge: description, significance, treatment]. / Pont myocardique description, signification, traitement.

The myocardial bridge is a well known anomalous trajectory of the coronary arteries, the significance of which has been discussed for a long time. It now appears that some myocardial bridges may cause myocardial ischaemia with clinical electrocardiographic, scintigraphic or metabolic signs--even myocardial infarction or sudden death. In these symptomatic cases, treatment is usually medical and rarely surgical. In the last few years, angioplasty and stenting have been used more frequently in cases resistant to medical therapy and appear to be an effective alternative to surgery.

[Hypertrophic cardiomyopathy: place and limitations of medical therapy]. / Cardiomyopathie hypertrophique; place et limites du traitement médical.

The development of echocardiography and kindred studies have enabled the detection of an increasing number of asymptomatic forms of hypertrophic cardiomyopathy. Drug therapy, by far the commonest therapeutic method of managing this condition, has only been shown to be effective on the symptoms. Therefore, due to the risk of iatrogenic disease, medication is only proposed to symptomatic patients: high dose betablockers is the usual treatment; when ineffective or contra-indicated, verapamil may be prescribed at progressively increasing doses under strict medical control. These products may need to be given at high doses in order to be effective but excessive bradycardia may be a limiting factor. Amiodarone alone or in association, may be preferred in forms with arrhythmias. The comparative efficacy of the different drugs, especially in preventing sudden death, requires well designed, controlled, therapeutic trials. Their results, if positive, would question the dogma of only treating symptomatic patients.

[Dynamic cardiomyoplasty: models of action and indications]. / Cardiomyoplastie dynamique: modes d'action et indications.

Cardiomyoplasty, proposed as an alternative to cardiac transplantation for the first time in 1985, has been carried out in over 500 patients over the world. The functional improvement after the procedure may be spectacular. The haemodynamic improvement at rest is generally small in terms of pre and postoperative ejection fractions. A dynamic effect of systolic assistance due to stimulation of the latissimus dorsi may be demonstrated in some cases by analysis of ventricular pressure-volume curves. However, it is probable that cardiomyoplasty prevents ventricular remodelling (girdling effect) and that chronic stimulation of latissimus dorsi, necessary to prevent atrophy and fibrosis, reduces wall stress. Therefore, many mechanisms, probably associated, may explain the clinical efficacy of cardiomyoplasty. Though the contraindications of this technique are now better known, its role with respect to cardiac transplantation in cases of severe congestive cardiac failure resistant to medical therapy still remain undefined.

[Surgical mitral valvuloplasty and dynamic left ventricular obstruction syndrome]. / Valvuloplastie mitrale chirurgicale et syndrome d'obstruction intraventriculaire gauche "dynamique".

The "dynamic" left ventricular outflow obstruction syndrome, which is found in 4.5 to 11 p. 100 of patients who underwent mitral valve repair by Carpentier's technique, seems to be due to the association of two different sets of circumstances. The first set is anatomical; the syndrome is thought to result from the implantation of a semi-rigid valve ring, from the excessive length of the mitral valve system in relation to the size of the ventricular cavity, and from excessive correction of mitral regurgitation with subsequent excessive reduction in caliber of the left ventricular outflow tract, change in the interrelation between outflow tract and ventricular filling and strongly anterior position of the mitral valve. The second set is functional; it is due to a more than 20 p. 100 reduction in caliber of the left ventricular outflow tract on the one hand, and to a more than 2.5 m/s increase in blood flow velocity on the other hand. These two phenomena may be produced by a decrease in left ventricular volume as a result of hypovolaemia, tachycardia or more rapid circulation. Treatment of the syndrome consists of correcting the associated abnormalities by prescribing a diet with a normal sodium content, together with an appropriate anti-arrhythmic agent and a beta-blocker.

[Should a main coronary artery be dilated when the controlateral vessel is occluded?]. / Faut-il dilater une artère coronaire principale lorsque l'artère controlatérale est occluse?

Angioplasty of the dominant left anterior descending or right coronary arteries when the controlateral artery is occluded may lead to major left ventricular dysfunction or cardiogenic shock. The authors assessed the results of angioplasty of a right coronary (n = 52) or left anterior descending (n = 141) artery stenosis when the controlateral artery was occluded and the left circumflex had no significant stenosis in 193 patients. The immediate and late (33 +/- 18 months) results were compared in 3 groups: the study group, a reference surgical group in which patients with comparable coronary lesions underwent double coronary artery bypass and a reference angioplasty group (n = 194) in which patients were treated by angioplasty of the right coronary and left anterior descending arteries. The left ventricular function of the study group was normal or midly abnormal in 72% of cases and moderately to severely abnormal in 28% of cases. During the hospital period, for the study group, there were 5.7% emergency coronary bypass procedures and 2.6% non-emergency bypass procedures, 1.6% of myocardial infarction and 0.5% deaths. After hospital discharge, the study group had 13.1% of coronary bypass procedures, 3.7% of myocardial infarcts and 4.7% deaths. The death and infarction rates were comparable in the 3 groups. The study group had a higher incidence of coronary bypass surgery in and after the hospital period than the control surgical group (p = 0.0.002). The authors conclude that dilatation of a main coronary artery when the controlateral artery is occluded is as safe as double coronary artery bypass surgery and angioplasty of the two vessels. Incomplete revascularisation in the study group did not affect survival rate without myocardial infarction compared with the angioplasty and surgical reference groups.

[Physical reproduction of cardiac sutures. A new field of investigation in cardiology]. / Reproduction physique des structures cardiaques. Une nouvelle voie d'exploration en cardiologie.

A new technique of physical reproduction of cardiac anatomy has been developed from volumetric data and its practical value assessed in cardiological practice. The acquisition of the volumetric data was by 3D echocardiography. Parallel and equidistant 2D views were selected from this information. The images were printed at a scale adjusted to the true dimensions of the structures of interest and then stuck on a support, the thickness of which was identical to the distance between the views, and the slices were superimposed while respecting the initial orientation. This technique has been adapted secondarily to modern industrial processes of rapid prototyping (3D printing and powdering) allowing automatic tooling of models. Several physical models have been made: whole heart in end diastole, mitral valve stenosis and prolapse, atrial septal defect with insertion of a percutaneous prosthetic device, great vessels at the base of the heart. There are many possible cardiological applications of physical models: investigation of complex cardiac disease, pre- and per-operative simulation of surgical procedures, elaboration of prosthetic material, physiopathological studies, teaching and training, patient information.

[Second degre Wenckebach phenomenon. Electrocardiographic and clinical study apropos of 10 cases]. / Le phénomène de Wenckebach du 2e degré. Etude clinique et électrocardiographique à propos de 10 cas

Study of atrio-ventricular conduction across the atrio-ventricular node using rapid atrial stimulation revealed a particular kind of block in 10 patients; the characteristics of the Wenckebach phenomenon were associated with a 2/1 block. One P wave was blocked, and the PR interval of the conducting sequence became progressively longer until the cycle was broken by two consecutive blocked P waves. By recording the potentials in the bundle of His, it proved possible to localise the conduction defect to the A/V node in 9 cases. The defect appeared in various clinical forms: atrial tachysystole, incomplete atrio-ventricular block, both chronic and acute, and atrio-ventricular conduction that was apparently normal. Study of the transmission through the node of progressively increasing atrial stimuli showed that there was a strong tendency towards diminishing conductivity which appeared to favour dispersion of the incoming impulses centrally within the node.