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Resume Les torsades de pointes sont des arythmies ventriculaires rares, particulieres par leur aspect (rotation des QRS autour de l'axe electrique), leurs circonstances d'apparition et leur traitement specifique. De durees variables, elles sont souvent repetitives, formant de veritables orages rythmiques. Quoique rapides, elles peuvent eventuellement passer inapercues lorsqu'elles sont breves, mais elles sont volontiers syncopales lorsqu'elles se prolongent et peuvent parfois degenerer en fibrillation ventriculaire. Elles surviennent dans un contexte d'allongement de l'intervalle QT d'origine acquise ou congenitale. Les formes acquises sont le plus souvent observees chez des sujets âges polymedicamentes ayant des antecedents cardiologiques, le plus souvent des femmes. Les causes de cet allongement sont une combinaison plus ou moins complexe de plusieurs facteurs (medicaments, bradycardie, hypokaliemie). Le traitement repose sur la suppression des facteurs de risques, l'administration intraveineuse (i.v.) de magnesium et, eventuellement, la stimulation ventriculaire rapide. L'utilisation ulterieure de medicaments allongeant QT chez ces patients ne pourra etre envisagee qu'apres avoir scrupuleusement evalue le rapport benefice/risque. Les formes congenitales apparaissent chez des sujets jeunes porteurs de mutations de certains canaux potassiques (Iks, Ikr) ou de leurs satellites et, beaucoup plus exceptionnellement, du canal sodique rapide. Dans le QT long congenital, la prevention du risque de mort subite repose sur le traitement β-bloquant, la stimulation ventriculaire ou le defibrillateur implantable et l'abstention de tout traitement retardant la repolarisation. Une enquete genetique doit etre realisee pour depister tous les porteurs de la mutation, car la mort subite peut en etre la premiere manifestation.

AF, a frequent and banal arrhythmia, is a debilitating and costly disease. The majority of patients with AF are aged 60 to 80 years, but the prevalence is as high as 10% after 80 years and the incidence increases in recent years in an "epidemic" way. AF is responsible for an excess of mortality with an relative risk between 2 and 4 depending of age and sex, especially as cardiovascular risk factors are associated. The morbidity is also important, with cerebral systemic embolism (2-3% per year), heart failure (1 patient for 3), and a total risk of hospitalization from 20 to 30% per year for AF patients with high cardiovascular risks. Whatever be the reasons for hospitalization, cardiovascular or not, in connection with AF or not, these reasons must be well analyzed, so that the risk of occurrence of hospitalization should reflect the efficacy of anti-arrhythmic drugs, or of their complications, or of the comorbidities associated with AF, so common in these older subjects. This morbidity-mortality composite endpoint should now be used in AF randomized trials, as occurring more frequently than mortality (4% per year) or embolic or hemorrhagic usual endpoints. Medico-economic consequences are significant and AF cost is almost 1% of total health spending, with 20% to 30% of the cost for anti-arrhythmic or anti-thrombotic drugs, and 50 to 60% for hospitalizations. Prevention of hospitalizations related to atrial fibrillation may represent a therapeutic target priority on the medico-economic ground.

Prior information in the realization of an invasive intervention is crucial. Indeed, the patient has to know theoretically his disease, diagnostic and therapeutic means, but also the risks of the used technique. The habits of information vary many from one center to another, in spite of the proposition of an information leaflet written by the French Society of Cardiology. Our aim was to evaluate the effectiveness of written information for patients hospitalized for coronary arteriography.Among patients hospitalized for realization of a programmed coronarography, a questionnaire was delivered before the information leaflet. The knowledge of the patients was so tested (27 items) before and after the reading of the information sheet (not limited time). The knowledge of the patients concerning coronarography indication, modalities, benefits, possible complications or still later possibilities was informed.Thirty-four patients were included: all knew hospitalization reason, 86% were men, middle-aged 65 (IC 95% 60-70). Thirty-four percent (15-54) had studied in higher education. Ninety-seven percent had had information before. Only 56% (38-74) were informed about the mode of anesthesia, 36% (19-53) duration, 69% (53-86) the injection of iodine, 44% the risk of allergy, 53% the risk of bruise, 15% of the cardiac risks, 21% the renal risks. Seventy-one percent knew the diagnostic benefits, 44% the possible coronary angioplasty, 17% the eventuality of a bypass surgery. The delivery of the information leaflet did not modify the knowledge on most of these items, in particular the modalities and the profits. The risks were known significantly better for the allergy (P=0.019), the bruise (P=0.018), the cardiac risks (0.001).The population benefiting from a coronarography considers to be enough informed. However, knowledge of the modalities, profits and risks is very low. The delivery of the consensual leaflet does not allow improving the situation, except as far as concerned the complications. Better information is so indispensable, not only to obtain a better support of the patient in the treatment, but also to prevent the forensic implications. The improvement of the information must be multifactorial, but usually used means could be not sufficient.

Acute pericarditis is a frequent hospitalization cause. A prospective, bicentric study aimed at different goals: population description, aetiologies screening, and evaluation of the interest of a coordinated and combined management between cardiologists and internists.Between May 2005 and September 2007, all patients admitted for acute pericarditis were prospectively enrolled. Physical examination, ECG, echocardiography, biological screening were performed. Patients were asked to consult both cardiologist and internist, one month later.Hundred and three patients were enrolled (mean age 43 years). Clinical outcome was classical in 60% of cases. ECG was typical in 59%. Troponin elevation was noted in 30% of patients. CRP was normal at diagnosis in 27% of patients, and increased significantly at first day (P=0.002). Possible cause was identified in 44 patients. In 26 patients (24.3%), precise diagnosis was performed: six cancers, one hemopathy, three connectivities, one EBV and one parvovirus B19 seroconversions, two untreated HIV patients, four inflammatory diseases, three endocrinology troubles, one oesophagitis, one dental sepsis, one amyloidosis, one acute pancreatitis, one declined dialysis indication. Eighteen de novo diagnoses (16.5%) were performed, out of them at least 12 benefited from specific management.Population of patients admitted for acute pericarditis are very heterogeneous. Our co-management between internists and cardiologists aims to diagnose earlier and easier curable diseases. Long-term follow-up remains of great interest, in order to diagnose later other disorders, which remained hidden, and to follow evolution of the population.

Faced with a cardiac arrhythmia occuring in an apparently healthy heart, it is necessary to perform an anatomical investigation to detect any unsuspected anomalies. Congenital cardiopathy must certainly be excluded, as this is often responsible for rhythm disorders and/or cardiac conduction defects. Similarly, any acquired conditions, cardiomyopathy, or cardiac tumour must be sought. However, the possibility should always be considered of a minimal congenital malformation, which could be repsonsible for: any type of cardiac arrhythmia: rhythm disorder or conduction defect at the atrial, junctional or ventricular level, with a benign or serious prognosis. Unexpected therapeutic difficulties during radiofrequency ablation procedures or at implantation of pacemakers or defibrillators. Together with rhythm studies, the investigation of choice is high quality imaging, either the classic left or right angiography or the more modern cardiac CT or intracardiac mapping.

Although anticoagulant treatment of atrial fibrillation is now well codified, the medical treatment of the fibrillation remains controversial. Two types of medication can be proposed: drugs to slow the rhythm (digitalis, betablockers and calcium inhibitors) and anti-arrhythmic mainly Class I or Class III drugs. Some doubt was raised in the 1990's about the pertinence of antiarrhythmic therapy and four recent trials (AFFIRM, RACE, PIAF and STAF) compared the two attitudes of "rhythm control" or "rate control" in atrial fibrillation. The four trials all showed that the results of these two options were equivalent with respect to the therapeutic objectives: reduction of mortality, thromboembolic or haemodynamic risk, and regression of symptoms and improvement of the quality of life. However, these trials have not closed the debate on these two therapeutic attitudes. In fact, analysis shows that the comparison was biased because anticoagulant treatment was inadequate and, though the treatment for rate control was appropriate, the antiarrhythmic treatment was far from being satisfactory and effective. Moreover, many patients in the "rhythm control" group were in atrial fibrillation whereas a certain number of patients in the "rate control" group were, in fact, in sinus rhythm throughout the study period. In addition, the comparison was incomplete because it did not include two other particularly common populations in clinical practice: multi-relapsing paroxysmal atrial fibrillation in healthy hearts and atrial fibrillation associated with severe left ventricular dysfunction, patients with cardiac failure. Until the results of trials currently under way (AF-CHF) become available, the authors discuss the use of drugs for rate control and antiarrhythmic therapy in everyday practice.

Among the unwanted effects of drugs, arrhythmogenic effects are particularly fearsome. Although rare they are serious, and responsible for syncope or sudden death, often linked with torsades de pointe on established long QT. For non cardiovascular drugs, detection is difficult because patients do not undergo systematic cardiological surveillance. Nevertheless understanding the risk, identification of predisposing factors, and consideration of the contra-indications are the rules of prescription, which are even more indispensable when the pathology being treated is benign. In effect, the implicated drugs are mainly anti-histamines, antibiotics, neuroleptics and antidepressants. The pharmaceutical companies, regulatory agencies, and pharmacological surveillance services must recognise the greatest possible risk of a drug, thanks to pre-clinical data, experimental electrophysiology both in vivo (measurement of the QT interval) and in vitro (action potential duration) or even in the elementary channel (essentially analysis of the iKr current). Correlated with clinical data (QT changes, pharmacokinetic interactions), a risk/benefit profile can therefore be established, which is even more demanding when the pathology is benign or when alternative drugs are available.

The mechanisms of action of antiarrhythmic drugs at atrial level are multiple. Antiarrhythmics may act at three levels in the prevention of paroxysmal atrial fibrillation: on the arrhythmogenic atrial substrate, the initiating extrasystoles including those of the pulmonary veins, and in the modulation of the autonomic nervous system. However, there are many modes of initiation which are not well understood so that the preventive role of the antiarrhythmic drugs remains imprecise. Cardioversion of persistent atrial fibrillation has been better analysed in healthy hearts: Class I antiarrhythmics in particular, despite their depressive effects on the conduction which are potentially arrhythmogenic, are beneficial by decreasing the number of reentry circuits, prolonging the atrial refractory period on short cycles and, paradoxically, by increasing the period of excitability in AF. All have a preferential action on anisotropic conduction, especially at the pivotal point of reentry. On the other hand, their role in electrophysiological remodelling in the prevention of immediate recurrences and in pathological atria, remains poorly understood. As for atrial flutter, despite many clinical and experimental studies with antiarrhythmics, the current predominant role of radiofrequency ablation greatly limits the value of these pharmacological studies.

A 29-year-old patient presented with Takayasu's arteritis which was revealed by heart failure, epilepsy, right hemiparesis and fever. Transient abnormalities of MRI and CSF (raised protein and cell content) were initially observed. The hypothesis of a hypertensive encephalopathy is suggested.

The PEPS study had the objective of documenting the acceptability and efficacy of propafenone in 1366 treated patients, after correction of chronic or paroxysmal AF, and followed up over one year. All the cases were validated by quality controls performed by the 196 participating cardiologists. All the events during follow up were validated by a committee of independent experts. The patients, aged 67 +/- 11 years, were in sinus rhythm on inclusion. Propafenone was prescribed at the initial dose of 600 mg/day in 65% of patients. The proportion of patients without relapse of AF was 64 +/- 1% at 12 months. After adjustment, the significant predictors of AF relapse were male sex, previous history of chronic AF and prescription of associated drugs. Neither patient age nor propafenone dose significantly influenced AF relapse. Seven deaths (0.5%) occurred during the study of which 3 were of unknown cause. A pro-arrhythmic effect was observed in 8 patients (0.59%) of which 6 had underlying heart disease. The overall frequency of pro-arrhythmic effects, including the 3 deaths of unknown cause, was therefore 0.81%. Tolerance of treatment with propafenone after correction of AF is therefore satisfactory and the frequency of pro-arrhythmic effects is less than 1%. The efficacy of the treatment for the maintenance of sinus rhythm is in accordance with previously published results.

Monophasic action potentials are currents recorded in vivo in the extracellular milieu which can reproduce the repolarisation signal of intracellular action potentials. For a long time unstable and complex to record, they now require simply a firm myocardial contact with a bipolar electrophysiological catheter and modification with recording filters, without a high-pass filter (DC). They have been widely used in recent years to study in vivo modifications of the action potential durations with frequency, epi-, endo-, or intramyocardial cellular topography, endocavity pressure modifications, or antiarrhythmic medication. They allow a unique means of continuous analysis in animals or in patients of the action potentials during polymorphic arrhythmias such as atrial fibrillation, ventricular fibrillation and torsades de pointes, although in these cases the refractory periods can not be measured precisely and continuously, beat after beat. In contrast, their clinical or experimental use in the study of arrhythmias dependent on premature post-depolarisations has without doubt been excessive and disputable, because it appears improbable that authentic premature post-depolarisations could ever be obtained on a monophasic action potential, which always represents the summation of the action potentials of dozens of cells.

A simple ECG curiosity or a precursor of serious arrhythmia, associated with pericardial effusion or a sign of inotropic alteration, the phenomenon of electrical alternans has intrigued clinicians and research workers in its multiple facets, mechanical and electrical, consequences on PR interval, QRS complex or ventricular repolarisation. As a consequence, the causal mechanisms are very different, but these last few years, a predominant role of calcium flux, especially intracellular, has been demonstrated. Recently, clinical interest in this phenomenon has been revived with the demonstration of micro-alternans of repolarisation, apparently a new marker for the risk of sudden death.

The objective of this study was to determine whether a small-size valve prosthesis contributes to exercise intolerance, as assessed by VO2 measurement during an exhaustive cycle ergometer exercise.The determinants of exercise capacity after mechanical aortic replacement are not well known. The selection of small valve sizes has, however, been described as an independent predictor of exercise intolerance as assessed by exercise duration. Maximal oxygen uptake (VO2max) is a good index of exercise tolerance.Fourteen patients were eligible, with a mean age of 62 +/- 6 years. Before surgery, the mean left ventricular ejection fraction (LVEF) was 73 +/- 8%. Two valve types with small diameter (19 to 21 mm) were used: Medtronic Hall and St Jude Medical. A healthy sedentary control group (n = 14) paired for age, weight and size was constituted. After one year of follow-up, cardiorespiratory tests were performed. In addition, the gradients through the prostheses were determined by continuous pulse Doppler at rest and immediately after the cardiorespiratory test. RESULTS The exercise tolerance was not significantly different between the control group and patient group: VO2 peak (21.7 vs. 20.4 ml/kg/min; p = 0.42), workloads (115 vs. 93 W; p = 0.13) and ventilatory parameters were similar. The mean and peak gradients at rest and during exercise were not correlated with VO2max.Valve replacement by small aortic prosthesis does not seem to be a factor of exercise intolerance as assessed by VO2max in patients without LVEF dysfunction before surgery.

In 1995, Wijffels and Alessie, using a curious goat model of atrial fibrillation, introduced the concept of atrial remodelling. The classical atrial substrate (anatomopathological-dilatation and hypokinesis-, and electrophysiological-short refractory periods and decreased conduction-), appeared not only to be one of the causes of atrial fibrillation but also the consequence of atrial fibrillation itself, the mechanism being a vicious circle. In addition to ventricular rhythmic cardiomyopathy, responsible for cardiac failure, the concept of atrial rhythmic cardiomyopathy with the same mechanical and electrophysiological consequences, has developed. These changes, characterised mainly by calcium overload associated with cellular hibernation and differentiation, have not been totally elucidated but have already renewed the physiopathology of atrial fibrillation.

We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K(+) current, I(K) (or Isus) by 69%. Dronedarone induced only a tonic block of I(K). Similar relative inhibitions of I(K) by dronedarone were obtained in young, sham, and PMI rats, even if I(K) was less in sham than in young and further reduced in PMI rats. The EC(50) values were 0.78 and 0.85 microM in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I(to). Time-to-peak and inactivation time constant of I(to) were decreased by dronedarone that also induced a marked slowing of I(to) recovery from inactivation. Similar effects were observed on the reduced I(to) recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K(+) currents and the increase in effective refractory period.

The hypothesis of immune and inflammatory activation occurring during chronic cardiac failure, capable of maintaining the disease, is supported by many experimental and clinical trials. Plasma cytokines levels, particularly the tumour necrosis factor alpha (TNF alpha), are raised at advanced stages of the disease, especially in cachectic patients. The correlations with other, more traditional markers, especially neurohumoral, are not very close, probably suggesting different mechanisms. Cytokines are a group of very different molecules with multiple, non-specific, and even beneficial effects. However, the lack of regulation in severe cardiac failure may lead to deleterious effects on the heart. The experimental effects of TNF alpha (mini-pumps, transgenic animals) include features of myocarditis, chamber dilatation and contractile dysfunction. Large scale therapeutic trials of long acting TNF alpha antagonists could confirm the "inflammation hypothesis" of mutual interaction between cardiac failure and the production of cytokines.

The genetics of the long QT syndrome are now better understood. However, there is much heterogeneity as three different genes have already been identified affecting the function of sodium and potassium channels. The aim of these recommendations is to draw up a list of drugs which are contraindicated or not recommended in patients with congenital long QT syndromes. The conraindicated drugs are those with which torsades de pointe have already been described. Drugs not recommended are substances which are not electrohysiologically neutral and for which, in view of their modes of action, their metabolism or belonging to a particular therapeutic class, make them very difficult to use in those patients. It is therefore better not to prescribe them whenever possible in this condition. These substances belong mainly to cardiovascular (especially antiarrhythmic), psychotropic, anti-infectious and antiallergic groups of drugs.

Low dose (5 to 10 micrograms/min) dobutamine echocardiography was used to predict the presence of reversible contractile dysfunction (myocardial stunning) after myocardial infarction successfully revascularised in the acute phase of primary angioplasty. The investigation was undertaken in 40 patients, 4 +/- 1 days after inaugural myocardial infarction. The left ventricle was divided into 16 segments. Viable myocardium was diagnosed when the initial regional wall motion score decreased by at least 2. Resting echocardiography was performed at 2 months to evaluate the effective recovery of regional wall motion (myocardial viability). The presence of contractile reserve was documented by dobutamine echocardiography in 18 patients (45%). The sensitivity, specificity and positive and negative predictive values of dobutamine echocardiography for the diagnosis of myocardial viability were 82, 83, 78 and 86% respectively. The negative predictive value was high in all dysnergic segments (86%). The positive predictive value of the investigation was however higher in hypokinetic than in akinetic segments (73 vs 21%; p0.05). The recovery of regional wall motion during follow-up was statistically related to higher initial left ventricular ejection fraction (p0.04), the presence of angiographically documented collateral circulation before revascularisation (p = 0.007), the contractile response to dobutamine (p = 0.0001) and was observed more frequently in hypokinetic than in akinetic segments (p0.05). These results show that low-dose dobutamine echocardiography is a sensitive and specific investigation for predicting irreversible myocardial damage after successful primary angioplasty in acute myocardial infarction. However, even in the absence of residual coronary stenosis, the presence of viable myocardium is only identified specifically in hypokinetic segments.

Most cases of dizziness or syncope referred to the emergency department or to services of internal medicine are caused by vasovagal syndromes. They comprise relative bradycardia with vasoplegia, the cardiovascular response to a neurological stimulus. It is possible to distinguish vagal or vasovagal syncope which is very common, the very stereotype reflex syncopes, carotid sinus hypersensitivity sometimes associated with sinus node dysfunction and borderline forms such as orthostatic sinus tachycardia and cerebrovascular syncope. The differential diagnosis is vast, from simple hysteria to severe cardiac disease. Tilt testing should be indicated for diagnosis of most cases of syncope with apparently normal hearts. Therapeutic abstention is the rule, providing certain preventive measures are taken, but, should treatment be necessary, cardiac pacing remains an exceptional modality in vasovagal syncope. Strict clinical and physiopathological studies are still required to determine the long-term prognosis and the underlying mechanisms of these syndromes.

The cardiac isoform of troponin I (cTnI) is a myofibrillar protein highly specific for myocardial injury. We used a recently developed new-generation immunoassay with high analytical sensitivity to measure cTnI in patients diagnosed with hematologic malignancies, before chemotherapy and after an intermediate cumulative dose of anthracyclines. We hypothesized that measurement of cTnI with this sensitive method would provide evidence of myocardial injury in these patients.Sera from 115 individuals (60 healthy controls, 25 anthracycline-naive patients and 30 patients treated with intermediate cumulative doses of anthracyclines) were assessed for cTnI, creatine kinase MB (CKMB) mass and myoglobin. Radionuclide left ventricular ejection fraction (LVEF) was also determined.Using this sensitive assay, detectable concentrations of cTnl were measured in the healthy population [mean, 19.5 pg/ml, 95% confidence interval (CI) 13.5-25.5 pg/ml]. Anthracycline-naive patients had cTnI mean values (36.5 pg/ml, 95% CI 25.1-47.9 pg/ml) that were significantly (P0.01) greater than those in the control group. cTnI was significantly (P0.00001) increased in anthracycline-treated patients (76.4 pg/ml, 95% CI 67.0-85.8 pg/ml) compared with both the anthracycline-naive patients and the controls. CKMB, myoglobin and LVEF were within the normal range in all patients.These data provide evidence for cardiac involvement in patients with hematological malignancies before and during the course of anthracycline chemotherapy. They suggest that detection of myocardial injury may be facilitated by measurement of cTnI with a highly sensitive assay.

ECG criteria which for many years formed the basis of the classification of regular atrial tachycardias may now be completed by the results of endocavitary studies (stimulation and mapping). Flutter is a macroreentry phenomenon in the right atrium, anticlockwise in typical, common or classical forms, and more variable in atypical forms: sometimes antidromic and clockwise, sometimes functional more rapid without a gap of excitability, or in other cases, skirting around the sears of atriotomy, especially right-sided. Tachycardias are paroxysmal and often secondary to reentry; more rarely permanent, they are then often due to increased automaticity especially in young patients. The concordance with surface ECG changes is not perfect and the distinction between flutter and tachycardia often depends on the frequency of the tachycardia and the leads studied.

During sinus rhythm, the successive responses to the application of electrical stimuli of increasing intensity during the vulnerable period are cardiac stimulations followed by repetitive ventricular responses and then ventricular fibrillation. An impulse of even greater intensity is not followed by ventricular fibrillation (shock at the upper limit of vulnerability) suggesting that defibrillatory shock is effective only when it does not reinduce fibrillation. Two other hypotheses are also proposed in fibrillation, that of critical mass and that of extension of the refractory periods, in particular after biphasic shocks. Clinically, the measurement of the threshold of defibrillation is difficult as it is a random process which does not obey the all or nothing principle. Ideally, a graph of efficacy versus energy should be constructed but this is only possible under experimental conditions. The effects of different antiarrhythmic drugs have been studied in this manner; in general, the sodium channel blockers improve the energies of defibrillation.

There are many electrocardiographic changes in sinoatrial block. Only 2nd and 3rd degree blocks can be analysed on surface recordings. However, they manifest themselves by pauses, the descriptions of which are rich and varied. They also vary according to the circumstances of apparition and the escape rhythms which accompany them. Related ECG changes such as chronotropic insufficiency or carotid sinus syndrome have been described. However, their significance is not univocal and only a precise analysis of the ECG recordings allows correct interpretation of the clinical and paraclinical signs and the institution of appropriate therapy.

Torsades de pointes is the most typical ventricular tachycardia involving QT-interval prolongation. It is a rather unusual but potentially lethal ventricular tachycardia with a distinctive morphology favored by bradycardia, antiarrhythmic drugs and hypokalemia and requires specific treatment. Torsades de pointes has been shown to be related to bradycardia-dependent early afterdepolarizations (EAD) and/or increased dispersion of repolarization. However, although EAD can be obtained relatively easily in vitro with quinidine or sotalol, torsades de pointes are very difficult to reproduce in animal models. The models of torsades de pointes which have been proposed can be categorized as morphological, EAD-related or pharmacological models. The purpose of the 'morphological' models was to reproduce the twisting of QRS axis typical of torsades de pointes, with no consideration of other aspects such as long QT or bradycardia. These models were produced by epicardial electrical or chemical (aconitine) stimulation at two distant ventricular sites or by overdosing of quinidine in dogs with acute myocardial infarction. The second type of model focused on the conditions producing EAD in vitro. Ventricular tachycardias were obtained in anesthetized dogs using toxics such as cesium or anthopleurine, both producing EAD in vitro. These ventricular tachycardias were shown to be sensitive to magnesium, heart rate and autonomic tone, but torsades de pointes remained rare, at least after cesium injections. The pharmacological models that could be used to study the QT-dependent proarrhythmic effects of drugs are the anesthetized rabbit with alpha-adrenergic stimulation, and the conscious dog model with chronic AV-block and diuretic-induced hypokalemia. Methoxamine-treated anesthetized rabbits develop ventricular tachycardias during clofilium infusions. These ventricular tachycardias, although appearing at very high heart rates, have typical torsades de pointes aspects and are often associated with giant QT waves. The specificity of the model remains to be tested. In our conscious bradycardic and hypokalemic dogs, quinidine and sotalol but not flecainide, propranolol or lidocaine induced QT-dependent arrhythmogenic effects and torsades de pointes. Efficacy of high rate stimulations and magnesium were repeatedly observed. This demanding model, especially designed for qualitative drug comparisons, is also well suited to studies on the mechanisms of initiation of torsades de pointes. The pertinence of these models for estimating the risk of QT-dependent proarrhythmias associated with non-antiarrhythmic agents remains to be tested.

Several experimental models of torsades de pointes have been proposed these last years. They can be classified in 2 categories: morphological models designed to reproduce the ECG features of "torsade", with in vivo ventricular stimulations or with computer ECG stimulations and pharmacological models designed to obtain in vivo early after depolarizations, with toxic agents such as cesium chloride and anthopleurine, or with commercialized or new pharmaceutical drugs. These models improved electrophysiologic and pharmacologic knowledge of torsades de pointes. The respective roles of early after depolarizations in torsades initiation and of reentry in the following beats of the salvos is now recognized. Induction protocols were described, which appeared to involve an inotropic potentiation following burst or repetitive extrastimuli. A more accurate evaluation of arrhythmogenic risk associated with new drugs could be developed.

In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block.

Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs' effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute poisoning with beta adrenergic inhibitors is rare although such drugs are widely prescribed. Between 1966 and 1980, 40 cases were recorded at the Fernand-Widal Toxicology Center. 40% of patients were asymptomatic and 25% had sinus bradycardia. 35% of patients had specific toxic signs, either atrioventricular block (20%) or hemodynamic disorders (15%); the latter were seen only when associated heart disease was present or when another cardiotropic agent had been absorbed. No deaths were recorded. This favorable prognosis may result from the self-limited nature of poisoning with beta blocking agents, myocardial function being similar to that which follows denervation. In severe cases, management includes pacing and glucagon.

Two patients were investigated for paroxysmal regular tachycardia with left bundle branch block centrifugation. A right-sided nodo-ventricular accessory pathway was demonstrated in both cases at electrophysiological investigation with His bundle recording and atrial and ventricular programd pacing techniques. However, the function of this pathway was different in the two cases. In the first case, there were no signs of an accessory pathway on the surface ECG in sinus rhythm but it could be unmasked by simple right atrial pacing at the same rhythm (widening of the QRS and shortening of HV from 40 to 25 ms). The tachycardias could be only initiated by ventricular extrastimulus. They showed major pre-excitation with left sided delay and a 1/1 atrio-ventricular response. There was no His potential before the ventriculogramme which retained the same configuration throughout the attack. The investigations also suggested the presence of a dual nodal pathway with the accessory pathway connected to the slow pathway. In the second case, the presence of an accessory pathway could be suspected from the appearance of the QRS complex in sinus rhythms. Tachycardia was initiated by an atrial extrastimulus with initially a first complex showing slightly more marked pre-excitation and a distinct His potential before the QRS but with a shorter HV interval than in sinus rhythm. Then the reciprocating tachycardia had appearances of major pre-excitation, left-sided delay and a 1/1 atrio-ventricular response. However, in contrast to the first case, all ventricular complexes were preceded by a His potential and the degree of pre-excitation was variable with a HV interval ranging from 0 to 15 ms. These two cases merit attention because of: --their points in common: nodal duality and an accessory pathway which was not atrio-ventricular (decremental conduction) but nodo-right ventricular, conducting well in the anterograde direction but more or less masked in sinus rhythm; the presence of the accessory pathway was clearly visible during reciprocating tachycardia; --the differences: in the first case the nodo-ventricular pathway formed part of the circuit of the reciprocating tachycardia which was antidromic: descending limb, the slow nodal pathway and then the accessory nodo-ventricular pathway; ascending limb, the His bundle and then the rapid nodal pathway. In the second case, the reciprocating tachycardia was entirely intranodal, the accessory pathway not being involved in the circuit but connected to it in parallel with the normal Hisian pathway.

The case reported here concerns an 80-year old man without history of coronary disease whose electrocardiogram showed localized and stable repolarization disorders, viz. elevated ST segment with isoelectric point J and negative T wave. This pattern suggested cardiac metastasis after chest examination had revealed a bronchial epidermoid carcinoma. Two-dimensional echocardiography showed that the lateral wall of the left ventricle was thickened, hyperechogenic and akinetic. The secondary cardiac lesions were confirmed at pathological examination. This case has prompted us to discuss the frequency of such secondary tumours of the heart, their mode of dissemination to the myocardium and their clinical and electrocardiographic aspects. It underlines the usefulness of echocardiography for the diagnosis of cardiac tumours.

Splitting of the His potential (H) in sinus rhythm is generally considered to be pathological but its significance during programmed atrial stimulation is not clear. This phenomenon was observed in 10 out of 53 patients aged between 19 and 45 years (average 31.8 years) not suspected of having paroxysmal intranodal block (asymptomatic, sinus rhythm without bundle branch block). Under basal conditions the H and the HV interval (35 to 50 ms; average 41 ms) were normal. Split H was observed with pacing periods of 680 to 885 ms (average 754 ms) and H1 H2 intervals of 325 to 450 ms (average 395 ms). The maximal interval between the split potentials ranged from 80 to 130 ms (average 100 ms). Splitting disappeared at the shortest periods when variable pacing cycles were used. The response to regular atrial pacing up to 150 bpm (10 cases) and to Ajmaline (1 mg/Kg) (4 cases) was normal. All patients but one were followed up to 10 to 41 months (average 21.4 months); the clinical and ECG parameters remained stable during this period. The presence of fragmented potentials between the atrial and ventricular complexes during programmed atrial stimulation may pose a difficult diagnosis problem, especially with respect to delayed atrial potentials. Splitting of the H is generally attributed to dispersion of the depolarisation wave front in the His bundle due to the persistence of the functional refractory state. Other mechanisms, especially longitudinal dissociation of the His bundle, may be discussed. From a prognostic point of view, this finding does not seem to carry more serious implications than simple lengthening of the HV interval or intranodal conduction delay, phenomena usually considered to be non-pathological.

A 25 year old patient presented with several types of paroxysmal tachycardia. Analysis of the recordings and the results of endocavitary electrophysiological investigation suggest the presence of nodoventricular and atrio-ventricular fibres. These two accessory pathways were latent in sinus rhythm but formed part of reentry loops. The reciprocating rhythms used the Kent bundle in the retrograde direction, and either the normal nodo-hisian or the Mahaim fibres in the anterograde direction. Simple echos ascending by the nodo-hisian pathway and descending by the nodo-ventricular pathway were also observed. The patient died of an unassociated cause and a pathological examination of the heart was performed. This confirmed the presence of a left posterior paraseptal Kent bundle and the presence of fibres relaying the inferior part of the atrioventricular node to the septal ventricular myocardium, this being made possible by a dehiscence of the central fibrous body.

We have evaluated the electrophysiologic effect of encainide and its three major metabolites, O-demethyl encainide, 3-methoxy-O-demethyl encainide and N-demethyl encainide in an anesthetized dog model. Our results support previous reports that O-demethyl encainide and 3-methoxy-O-demethyl encainide are both more potent than encainide in the depression of conduction. We also have shown that N-demethyl encainide is of about equal potency to encainide. Whereas the major differences between these compounds is primarily one of potency, there are some qualitative differences. Although O-demethyl encainide did not change the ventricular or atrial effective refractory periods significantly, 3-methoxy-O-demethyl encainide and N-demethyl encainide prolonged both. Encainide increased the atrial effective refractory period but did not produce significant changes in the ventricular refractory period. These data support previous suggestions of an important role for these metabolites as modulators of the clinical efficacy of encainide.

The aetiology and evolution of chronic infranodal atrioventricular block (AVB) of young patients are not well known: are they the first sign of subclinical myocardial disease which can only be diagnosed by long term follow-up or do they represent isolated degenerative disease of the conduction tissue (Lenegre's disease)? Eighteen patients (15 men, 3 women) aged 25 to 49 years (average 41.5 years) were followed up for periods of 2 to 20 years (average 7.33 years) after pacemaker implantation for syncopal AVB. Follow-up was focused on the evolution of the conduction defects and the cardiovascular status. The patients were divided into two groups at the initial assessment: Group I: 15 patients with documented AVB; Group II: 3 patients in whom all basal recordings showed sinus rhythm (SR). Apart from one patient with an early non-ischaemic dilated cardiomyopathy, there was no previous cardiovascular disease. There was no history of ischaemic heart disease, drug effects, infection or inflammation in favour of an acute AVB. Three patients had permanent AVB, either 2nd degree with bundle branch block (N = 2) or 3rd degree block (N = 1). The other 15 patients were in sinus rhythm with bundle branch block: left bundle branch block (LBBB) in 5 cases, right bundle branch block (RBBB) in 3 cases; RBBB with left anterior hemiblock in 5 cases, RBBB and left posterior hemiblock in 2 cases. Paroxysmal AVB was recorded in 12 of these 15 patients on at least one occasion.(ABSTRACT TRUNCATED AT 250 WORDS)

Sotalol is a beta-blocking agent endowed with class III electrophysiological properties. It has proved clinically effective in the treatment of arrhythmia, but episodes of torsades de pointe have been observed, particularly (though not exclusively) in the presence of hypokalaemia. The effect of sotalol with or without hypokalaemia was studied on a recently developed model for experimental torsades de pointe. Conscious dogs with complete atrioventricular block (ventricular cycle RR = 1530 +/- 170 ms) and provided with permanent atrial and ventricular epicardial electrodes were given sotalol intravenously either as a 4.5 mg/kg bolus injection or as a 1.5 mg/kg/h infusion. Group I dogs (n = 8) had normal blood potassium levels (4.3 +/- 0.1 mEq/1); following sotalol (plasma concentration 3.7 +/- 0.2 micrograms/ml) the ventricular rhythm was electrically driven to 25/min (RR = 240 ms) and QT was increased by 68 +/- 11 ms; torsades de pointe occurred in 5/8 animals (62 p. 100). Group II dogs (n = 6) had diuretic-induced hypokalaemia (2.6 +/- 0.1 mEq/1); following sotalol (plasma concentrations 3.8 +/- 0.3 micrograms/ml) the ventricular rhythm also depended on an external pacemaker to reach 25/min (in all but 1 dog) and QT increased by 46 +/- 11 ms; torsades de pointes were obtained in 5/6 animals (83 p. 100). These torsades de pointe were prevented in every case by rapid ventricular pacing (100-120/min). Thus, the pro-arrhythmic effects of sotalol were very frequent on this experimental model, but hypokalaemia was not necessary for torsades de pointe to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of a congenital aneurysm of the right anterior sinus of Valsalva (ASV) extending into the septum is reported. The patient, a 20 year old male Central-African, presented with syncopal complete atrioventricular block (AVB) or recent onset. There were no clinical or radiological signs of associated cardiac disease. After implantation of a pacemaker, the diagnosis of an ASV extending into the septum was suggested on routine M mode echocardiography. It was confirmed by two-dimensional echocardiography and aortography. These investigations provided data on its size, its relationship to the cardiac chambers and also showed absence of rupture. The neck of the aneurysm was closed by an endo-aortic approach. There was moderate postoperative aortic regurgitation. This case underlines the value of systematic echocardiography in young patients with AVB of recent onset and obscure origin.