[Value of left atrial dilation in the diagnosis of silent myocardial ischemia in diabetes mellitus patients]. / Facteurs prédictifs de l'existence d'une ischémie myocardique silencieuse chez le patient diabétique. Intérêt de l'évaluation de la surface de l'oreillette gauche.

BACKGROUND: Accelerated atherothrombosis is a common feature in diabetes mellitus patients (DM), which can be related to abnormalities in vascular cell apoptosis and activation leading to the release of procoagulant microparticles (MPs). In DM patients, we hypothesized that circulating levels of biomarkers involved in atherothrombosis processes as well as cardiac and carotid echocardiography variables could be useful in the detection of silent myocardial diagnosed by myocardial perfusion imaging. METHODS AND RESULTS: We investigated, in 55 patients with diabetes (mean age 62+/-10 years) and 15 nondiabetics (46+/-14 years) patients the prevalence of silent myocardial ischemia (SMI) detected by a treadmill exercise or dipyridamole (99m)Tc-sestamibi stress test. Echocardiographic and -carotid variables were obtained using standardized methods. Biomarkers assessing endothelial apoptosis or activation (CD31+-MPs, CD62+-MPs, VCAM-1), inflammatory status (CD11a +/- MPs, MCP-1, CRP), platelet activation (GPIb+/-MPs, CD40-L, P-selectin, GPV) ventricular stretch (BNP) were measured in the plasma. SMI was diagnosed in 23/55 (42%) diabetics patients and in 3/15 (20%) nondiabetics patients. Enhanced inflammatory status and leukocyte damage (CD11a+-MPs) were evidenced in diabetic patients. Within the diabetic population, biomarkers levels of atherothrombosis were not significantly associated to the detection of SMI. In multivariable analyses adjusted for LV hypertophy, left atrial surface (LA) remained independent predictor of silent myocardial ischemia (OR 4.14; IC [1.7-16.13]; P=0.039). CONCLUSIONS: In diabetes mellitus patients, LA surface independently predicted silent myocardial ischemia after adjustment for established echocardiographic, and inflammatory risk factors. This simple measure of LA dilation could be helpful in the identification of diabetes mellitus patients at heightened cardiovascular risk.

[Platelet response to aspirin and clopidogrel. Biochemical evaluation, clinical impact, and pharmacological modulation]. / Réponse plaquettaire à l'aspirine et au clopidogrel. Evaluation biologique, impact clinique, modulation pharmacologique.

In the vasculature, platelets contribute to thrombotic and inflammatory responses, key processes in atherothrombosis. During percutaneous coronary interventions, several studies have emphasized the deleterious impact of enhanced platelet aggregation on early clinical outcome. However, despite the significant interest of determining platelet responsiveness appears worth, the clinically accurate and practical platelet function assay is still not widespread available. Furthermore, standardized definitions of platelet "low-responders" are still lacking. Up to now, light transmission platelet aggregometry remains the "gold-standard". Platelets "points of care" assays might overcome the limitations of conventional optical platelet aggregation but need further validation in clinical settings. The most recent ACC/AHA guideline endorses a strategy of platelet monitoring in the highest risk patients (IIb C). In "low-responders" patients, clopidogrel dose escalation was demonstrated to improve platelet responsiveness. Others potential pharmacological solutions could include the switch for another thienopyridine. Indeed, prasugrel a P2Y12 receptor inhibitor was demonstrated to provide higher levels of inhibition of ADP-induced platelet aggregation.

[Platelet responsiveness to clopidogrel in patients with coronary syndrome. Comparison of platelet aggregation induced by ADP and flow cytometric analysis of intraplatelet VASP phosphorylation]. / Evaluation de la réponse plaquettaire au clopidogrel au cours des syndromes coronariens. Comparaison de l'agrégométrie à l'ADP et de la méthode VASP.

UNLABELLED: Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation. OBJECTIVES: (i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI > 67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM) < to 30%. RESULTS: PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P < 0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia. CONCLUSION: During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation.

[Microparticles and cardiovascular disease]. / Microparticules et pathologies cardiovasculaires.

Microparticles are membrane fragments liberated by activated or apoptopic cells. Thought for a long time to be cellular debris with no specific biologic function, in the vascular compartment they are a circulating reservoir of cellular effectors involved in thrombosis, inflammation, vascular remodelling and angiogenesis. High concentrations of circulating procoagulating microparticles found in many cardiovascular diseases indicate the importance of platelet, endothelial and monocytic activation and could contribute to the persistence of atherothrombotic disease. Pharmacological modulation of circulating microparticle concentrations could become a major therapeutic target in the future.

[Variable extent of platelet responsiveness to clopidogrel inhibition: "clopidogrel resistance"?]. / Variabilité de la réponse plaquettaire au clopidogrel: "résistance" biologique?

During percutaneous coronary angioplasty, platelet inhibition by clopidogrel and aspirin has drastically decreased the risk of thrombotic occlusion of the stented vessels. However, despite the widespread use of these drugs, the incidence of acute or subacute stent thrombosis remains elevated, concerning 1 to 2% of the treated patients. Considerable differences in the responsiveness to clopidogrel could be observed, suggesting a possible underlying biological resistance. "Clopidogrel resistance" has recently been associated to an increased risk of thrombotic events following coronary angioplasty. Variations in enteric absorption, biotransformation in the liver by the CYP3A4, changes in the ADP receptor P2Y12, abnomalies of intraplatelet signal transduction, extent of platelet activation, class angina, diabetes mellitus may account for the considerable interindividual response variability widely reported. In this view, laboratory tests evaluating "clopidogrel resistance" might be useful tools for the identification and follow-up of patients at higher thrombotic risk. Indeed, in these patients, further platelet inhibition can be achieved by higher doses of clopidogrel.

Myocardial bridging as a cause of acute transient left heart dysfunction.

The significance of myocardial bridging is still a matter of debate, and although several reports have underlined its pathologic potential, myocardial bridging is often considered to be a benign phenomenon. We present here the case of a 63-year-old woman with a history of acute left heart failure and ECG evidence of ischemia, and whose primary abnormality on extensive workup was myocardial bridging. This case further underlines that myocardial bridging can lead to significant cardiac events.

Anatomic, clinical, and therapeutic features of acute cardiac rupture. Successful surgical management fourteen hours after myocardial infarction.

A 62-year-old man sustained an acute myocardial infarction complicated on the thirteen hour by left ventricular rupture and acute periocardial tamponade. Echocardiography confirmed the suspicion of intrapericardial fluid, and immediate pericardiocentesis improved the hemodynamic state for a period sufficient to permit preparation for operation. Resection of ruptured and necrotic anteroapical left ventricular myocardium with primary reconstruction was successfully accomplished with the aid of temporary extracorporeal circulation. The patient has remained well for 1 year after the operation. Anatomic, clinical, and therapeutic features of acute cardiac rupture are discussed.

Diltiazem slow-release and left-ventricular hypertrophy: a volumetric approach of left ventricular mass using magnetic resonance imaging.

AIMS: This study was designed to assess the changes in left ventricular mass (LVM) in hypertensive patients with left ventricular hypertrophy under drug therapy with once-daily slow-release diltiazem. Magnetic resonance imaging (MRI) was used for this purpose because of its higher reproducibility than M-mode or two-dimensional echocardiography. METHODS: Patients suffering from essential hypertension were included if their baseline LVM index (LVMI) was > or = 105 g/m2 in male or > or = 85 g/m2 in female patients, ie, equal or higher to the median values observed in hypertensive patients in our institution. MRI consisted in a true short-axis, electrocardiogram (ECG) gated spin-echo slice acquisition at baseline, after 3 and 6 months of therapy (M0, M3, and M6). Data were stored on magnetic tapes and read subsequently under blind conditions and the control of an external auditor. RESULTS: Thirty-five patients were included. Of these, 14 patients (40%) were not previously treated. Inter- and intra-observer variability for LVMI measurement were 5.6 +/- 4.3% and 2.1 +/- 3.0%, respectively. Mean baseline LVMI was 110 +/- 16 g/m2 in male and 96 +/- 16 g/m2 in female patients. It decreased by 3.6% at M3 (P = 0.05) and by 6.0% at M6 (P = 0.02). A trend towards a greater LVMI reduction was observed in previously untreated patients. CONCLUSION: This study confirms that MRI is a reproducible technique for the measurement of LVM. It demonstrates a significant reduction in LVMI as early as the 3rd month of therapy in hypertensive patients treated with once-daily sustained release (SR) diltiazem, although baseline LVMI in the majority of participating patients was only moderately increased.

Acute post-infarction left ventricle rupture. Five operations with three long-term survivals.

Cardiac rupture is cause of death in myocardial infarction. Surprisingly only seventeen successful attempts at operative treatment have been published, with a rather good long term survival. The authors report five cases of cardiac rupture operated upon with two deaths and three long term survivals. Frequency, clinical features and surgical possibilities are discussed with particular insistance on a rather aggressive surgical attitude when considering this complication.

[Should cardiac insufficiency be first treated by angiotensin converting enzyme inhibitors?]. / Faut-il traiter les insuffisances cardiaques par les inhibiteurs de l'enzyme de conversion en première intention?

Chronic cardiac failure is an important problem of public health because of its prevalence and high mortality. A better understanding of its physiopathology and the detrimental effect of neurohormonal activation that it induces were the reasons for the utilisation of angiotensin converting enzyme inhibitors leading to symptomatic improvement and also a reduction in the mortality of severe cardiac failure, as demonstrated in the CONSENSUS study published 5 years ago. Since then, cardiologists have presented ACE inhibitors in all stages of cardiac failure, but is this attitude justified? More explicitly, are ACE inhibitors the drugs of choice in cardiac failure? Before acknowledging this label "drug of choice" in the treatment of chronic cardiac failure, ACE inhibitors should fulfill certain reference criteria proposed by Packer for the treatment of this condition: rapid relief of symptoms; reduced mortality; modification of the natural history of the condition; efficacious and well tolerated. The effects of ACE inhibitors are analysed critically taking into account the results of large scale therapeutic trials (SOLVD, V-HeFT II, CONSENSUS II, SAVE), which have been reported recently? The reported results confirm clinical impressions: ACE inhibitors are the drugs of choice of all stages of chronic cardiac failure but in association with diuretic and digitalis therapy.

[Terminal heart failure; therapeutic strategies. Drug therapy in cases of absence of possibility of heart transplantation: dobutamine therapy, aspects of compassion?]. / Insuffisance cardiaque terminale; stratégies thérapeutiques. Moyens médicaux en l'absence de possibilité de greffe cardiaque: cure de dobutamine, aspects compassionnels?

Terminal cardiac failure, despite the gain obtained by angiotensin converting enzyme inhibitors, continues to carry a high annual mortality. Cardiac transplantation, with a 1 year survival of about 80% (a result which is sustained at 5 years), constitutes the treatment of choice for these patients. However, in view of the contraindications to transplantation and the cruel lack of donors organs, many cases of terminal cardiac failure are unable to benefit from transplantation. What are the pharmacological means available for these patients? This is a real therapeutic challenge. The essential objective in the management of these patients with a poor short-term prognosis is the reduction of mortality. However, this aim is not easily attained, at least in the short or medium-term in the present state of our knowledge. Other objectives can therefore by legitimately considered in the management of patients with cardiac failure in the terminal phase: the most important ones are to improve symptomatology and the quality of life. Terminal cardiac failure is a complex syndrome implicating a number of non-cardiac abnormalities. They may not only participate in the symptomatology and high mortality, but also make therapeutic management a delicate operation. Nevertheless, the abnormalities of cardiovascular function remain the cardinal problem. The treatment which we use aims to correct them. The authors propose a review of the possibilities available with reference to data in the medical literature.

[The timing of cardiac transplantation]. / L'heure de la greffe cardiaque. Transplantation cardiaque.

The considerable progress realised over the last 20 years in the domain of cardiac transplantation has had, as a corollary, an ever increasing demand and a cruel shortage of available grafts, responsible for a high mortality of some of the candidates on the waiting list. This situation justifies a review of the objective criteria of eligibility for a more pertinent attribution of donor organs. A review of the recent literature suggests a logical process in the evaluation of candidates. The first step consists of optimisation of medical therapy. This allows classification of patients with respect to the clinical condition obtained, which may be "critical", "unstable" or "stable" and thereby retain the indication for transplantation in the first two groups in the absence of a contra-indication. The timing of the transplantation is more difficult to determine for the 60% or so of patients with a low ejection fraction and who have been stabilised. The measurement of peak VO2 on exercise, which appears to be the most powerful prognostic variable in these patients, with respect to a normal subject of the same age, allows identification of urgent indications for transplantation. Moreover, a 3 monthly follow-up of peak VO2 of patients on the waiting list or deferred also enables reconsideration of their inscription or non-inscription.

[Prognosis of diastolic cardiac insufficiency]. / Pronostic de l'insuffisance cardiaque diastolique.

The natural history and prognosis of diastolic cardiac failure are difficult to determine because of the large differences in the studies which have been performed in this field. The ten studies published to date concerning the prognosis have been performed on hospital populations and, consequently, only the most severe cases have been recruited. Moreover, the threshold values of indices of the ejection phase used to define systolic dysfunction vary from one study to another. A review of these papers provides a rather disconcerting appreciation of the annual mortality rate (from 1.3% to 17.5%). The differences in aetiology, age and threshold values of parameters of systolic function probably explain most of the variability observed. Taking unbiased studies alone in consideration, such as the Framingham study, the mean annual mortality of diastolic cardiac failure between 55 and 71 years, is 3 to 9%, much less than that observed with predominantly systolic dysfunction (15 to 20%). Other prospective studies, adjusting morbidity and mortality to age and other principal prognostic factors, are awaited.

[Left ventricular diastolic dysfunction in cardiomyopathies]. / Dysfonction ventriculaire gauche diastolique dans les myocardiopathies.

Although physiologists have recognised for many years that cardiac performance is based on two functions, systolic and diastolic, it has only been in the last 15 years that clinicians have acknowledged the essentiel role of diastole in the physiopathology of cardiac disease. Many studies have shown that left ventricular diastolic dysfunction resulting from abnormal active relaxation or changes in passive visco-elastic properties of the myocardium modulating its rigidity were responsible for decreased distensibility of the ventricle and an increase in its filling pressures. Therefore, the symptoms of the majority of patients with cardiomyopathy are due, more or less, to diastolic dysfunction. This is particularly the case in hypertrophic cardiomyopathy, most case of which have diastolic dysfunction secondary to an often asymetric distribution of the hypertrophy, to the disorganisation of the myocardiofibres and to interstitial fibrosis. With respect to advanced forms of restrictive cardiomyopathy, as their clinical and haemodynamic characteristics resembling constrictive pericarditis show, they demonstrate caricatural diastolic dysfunction. Finally, although the main abnormality in dilated cardiomyopathies is poor contractility, a decrease in ventricular compliance is constantly observed.

[Heart failure and vasopeptidase inhibitors]. / Insuffisance cardiaque et inhibiteurs des vasopeptidases.

The morbidity and mortality of cardiac insufficiency remains such that it justifies the pursuit of finding new drugs and new sensitive techniques to slow or abolish its evolution. Bringing the vasopeptidases, such as omapatrilat, up to date results in a rational process aimed at simultaneously modulating certain interactive humoral systems. They represent drugs which simultaneously inhibit neutral endopeptidase and angiotensin converting enzyme with the effect of potentiating the natiuretic peptide system and bradykinin, and blocking the conversion of angiotensin I and angiotensin II. In the IMPRESS study, omapatrilat has been evaluated in patients with cardiac insufficiency versus lisinopril; there was no significant difference on the principal outcome measure which was exercise tolerance, however it was significantly more effective than lisinopril on the outcome measure combining death and hospital admission for deteriorating cardiac insufficiency. A wider study is underway, the OVERTURE study, which is evaluating omapatrilat versus enalapril on hospital admission and all-cause mortality. The Vanlev dossier has not yet been submitted to the regulatory authorities for obtaining its authorisation to be put on the market.

[Echocardiographic abnormalities in the mitral valve prolapse syndrome]. / Les anomalies échocardiographiques dans le syndrome du prolapsus des valves mitrales

Eight patients with prolapsed mitral valve syndrome, with a mid - or - end - diastolic click or murmur, underwent echocardiographic examination using ultrasound. Examination of the displacement of the valves by the "time motion" method showed all cases to have an abnormal recoil; in 6 cases this occurred in mid or late systole, and in two from the beginning of systole. The recorded amplitude of the pathological displacement, which gives the systolic tracings a domed appearance, and the consistancy with which it could be recorded (irrespective of the incidence of the ultrasonic waves), seem to afford a method for evaluating the degree of prolapse which, in most cases, involves both the valves. The authors compare their results with those which have already appeared in the literature, and emphasise the very real contribution which echocardiography can make in the diagnosis and assessment of the prolapsed mitral valve syndrome.

[Familial forms of the mid-end systolic click and murmur syndrome with deviations of left ventricular kinetics]. / Formes familiales du syndrome "click et souffle méso-télésystoliques" avec anomalies de la cinétique ventriculaire gauche

The aetiology and pathogenesis of the "mid/end-diastolic click and murmur" syndrome, with prolapse of the mitral valves, is obscure in most cases. However, the fact that some cases have had a familial distribution is evidence in favour of a dysgenetic origin. Seven new cases of this type are reported. The authors suggest in this paper that the incidence of the familial form of the syndrome is greater than the literature seems to suggest, and that the syndrome is likely to be due to a malformation. They also emphasise the important part which echocardiography plays in its diagnosis and investigation. Finally, the finding on cine-angiocardiography of specific abnormalities of left ventricular function similar to those found in other studies is indicative of a primary myocardial disorder, associated with subsequent structural alterations of the valvular mechanism.

[Familial mitral valve prolapse and syncopes caused by ventricular tachycardia]. / Prolapsus valvulaire mitral familial et syncopes par tachycardie ventriculaire

The authors report the case of a female aged 40 who was subject to syncopal attacks, and had an apical end-systolic murmur. The presence of an idiopathic prolapse of the mitral valve was demonstrated, as well as the familial nature of the condition, and the fact that the syncopal attacks were caused by ventricular tachycardia, The case report is followed by a discussion of the cardiac arrhythmias which are likely to accompany this particular mitral lesion, the difficulties in treatment which arise, and finally the danger of sudden death by ventricular fibrillation inherent in this condition, a danger which it is stille difficult to quantify.

[Drug therapy of acute myocardial infarction without cardiogenic shock and thrombolytic therapy excluded]. / Les traitements médicamenteux de l'infarctus aigu du myocarde en dehors du choc cardiogénique et à l'exclusion de la thrombolyse.

Myocardial infarction is responsible for 25,000 deaths per year in France and is a real problem of public health. The management of patients victims of this condition is an important feature of medical practice. Thrombolytic therapy has resulted in significant improvements in the reduction of the size of the infarct, in the conservation of left ventricular function and in the reduction of mortality. Treatment of the acute phase of myocardial infarction, especially when there are contra-indications to thrombolysis, comprises other approaches, some of which are old, which are reviewed in the light of the results of the latest large scale therapeutic trials.

[Value of transesophageal auricular stimulation for evaluating the accessory pathway and effect of treatment in Wolf-Parkinson-White syndrome]. / Intérêt de la stimulation auriculaire transoesophagienne pour évaluer la voie accessoire et l'effet du traitement dans le syndrome de Wolff-Parkinson-White.

In order to assess the value of the various atrial pacing techniques employed to evaluate the anterograde conduction of the accessory pathway and the effect of antiarrhythmic agents in Wolff-Parkinson-White syndrome, transesophageal atrial pacing was performed in 12 patients before and during treatment with oral flecainide acetate in doses of 200 mg per day. Before treatment, the shortest interval conducted with a 1/1 atrioventricular conduction by the accessory pathway ranged from 225 to 600 ms (mean 311 +/- 98 ms), and the effective refractory period of the accessory pathway, measured by the extrastimulus method in 11 patients, varied from 240 to 320 ms (mean 273 +/- 22 ms). These two values were very close in each patient and correlated well with each other (r = 0.90; p less than 0.001). Atrial fibrillation could be induced in 3 patients. Three patients were considered "at risk" since their effective refractory period or minimal R-R interval in atrial fibrillation was 250 ms or less. Tachycardia was induced in 8 patients, and it was possible to induce arrhythmias in the 6 patients for whom we had recordings in spontaneous tachycardia. Under treatment with flecainide acetate, an anterograde conduction block appeared in 3 patients. In the remaining 9 patients the shortest interval conducted with a 1/1 atrioventricular conduction by the accessory pathway was longer in every case: it ranged from 270 to 540 ms (mean 407 +/- 84 ms; p less than 0.001), which corresponded to a 20 to 240 ms prolongation (mean 133 +/- 78 ms).(ABSTRACT TRUNCATED AT 250 WORDS)