Pregnancy and newborn outcomes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

INTRODUCTION: The prognosis of pregnancy in patients with Arrhythmogenic Right Ventricular Cardiomyopathy/dysplasia (ARVC/D) is poorly documented. The aim of this study is to assess the cardiac risks during pregnancy and the impact of ARVC/D on fetuses/neonates/children. METHODS: We included all ARVC/D women with a history of pregnancy from the ARVC/D Pitié-Salpêtrière registry. Cardiac and obstetrical events having occurred during pregnancy/delivery/post-partum periods and neonatal data/follow-up were collected. RESULTS: Sixty pregnancies in twenty-three patients were identified between 1968 and 2016. Only two major non-fatal cardiac events (one sustained non-documented tachycardia and one ventricular tachycardia) were recorded during pregnancy in two different mothers (3% of pregnancies, 9% of mothers). None occurred during delivery or in the postpartum period. No mother developed heart failure. Beta-blocker therapy during pregnancy (n=15) was associated with lower birthweight (2730 vs 3400g, p=0.004). Only two preterm deliveries occurred, unrelated to cardiac condition. Caesarean section was performed in 13% of cases. Premature sudden-death occurred in 10% (n=5) of children before 25years-old including two in the first year of life. CONCLUSION: ARVC/D is associated with a low rate of major cardiac events during pregnancy and vaginal delivery appears safe. The risk of sustained ventricular arrhythmia seems poorly predictable and supports the continuation of beta-blockers during pregnancy. Major cardiac events were frequent in childhood, justifying close cardiac monitoring.

Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.

BACKGROUND: Atrioventricular block (AVB) is common after transcatheter aortic valve replacement (TAVR) and permanent pacemaker (PPM) implantation is needed in up to 30% of patients. Main predictors of long term AVB are electrocardiographic. The purpose of this study is to assess the prognostic value of serial HV intervals measured before and after TAVR to shorten the timing of PPM implantation. METHODS: His bundle recordings were performed before (HV1), immediately after TAVR (HV2) and at day 2 for Edwards Sapien (ES) and 5 for Medtronic CoreValve (CV) (HV3). PPM indications were high degree AVB before day 5 or prolonged HV interval ≥80ms at the last recording. High degree AVB after discharge was evaluated from the pacemaker memories and ECG at 1 and 6months. RESULTS: Data were obtained in 84 patients (33% CV and 67% ES). HV values were not associated with early or late AVB. PPM were implanted in 27 patients (34%) for documented AVB (n=17, 24%), prolonged HV interval (n=9) or sick sinus syndrome (n=1). Persistent complete AVB during the procedure and postoperative high degree AVB were the only perioperative factors associated with further long term occurrence of high degree AVB (p=0.001 and p<0.001). On multivariate analysis, only postoperative high degree AVB was significant (p=0.001). CONCLUSION: Pre- and post-operative HV measurements were not correlated with late AVB after TAVR. Perioperative persistent complete AVB and postoperative high degree AVB are the only factors to predict late AVB and should be considered for the decision of PPM implantation.

Dexrazoxane protects the heart from acute doxorubicin-induced QT prolongation: a key role for I(Ks).

INTRODUCTION: Doxorubicin, an anthracycline widely used in the treatment of a broad range of tumours, causes acute QT prolongation. Dexrazoxane has been shown to prevent the QT prolongation induced by another anthracycline, epirubicin, but has not yet been reported to prevent that induced by doxorubicin. Thus, the present study was designed to test whether the acute QT effects induced by doxorubicin could be blocked by dexrazoxane and to explore the mechanism. Results were compared with those obtained with a reference human ether-a-go-go (hERG) channel blocker, moxifloxacin. METHODS: The effects of moxifloxacin (100 microM) and doxorubicin (30 microM), with or without dexrazoxane (from 3 to 30 microM), have been evaluated on the QTc interval in guinea-pig isolated hearts and on I(Kr) (rapid component of the delayed rectifier current) and I(Ks) (slow component of the delayed rectifier current) currents stably expressed in human embryonic kidney 293 cells. RESULTS: Moxifloxacin (100 microM), a potent hERG blocker, prolonged QTc by 22%, and this effect was not prevented by dexrazoxane. Doxorubicin (30 microM) also prolonged QTc by 13%, did not significantly block hERG channels and specifically inhibited I(Ks) (IC(50): 4.78 microM). Dexrazoxane significantly reduced the doxorubicin-induced QTc prolongation and prevented doxorubicin-induced inhibition of I(Ks). CONCLUSION AND IMPLICATIONS: Doxorubicin acutely prolonged the QT interval in guinea-pig heart by selective I(Ks) blockade. This effect was prevented by dexrazoxane. This result is important because it illustrates the danger of neglecting I(Ks) in favour of hERG screening alone, for early preclinical testing for possible induction of torsade de pointes.

[Survey into cardiac pacing in the Ile-de-France area for the year 2001: evaluation of indications]. / Enquête sur la stimulation cardiaque en Ile-de-France pour l'année 2001: evaluation des indications.

UNLABELLED: A survey into the implantation of cardiac pacemakers during 2001 in the Ile-de-France area was carried out by the French National Insurance Medical Service in order to evaluate performance in all centres performing more than 10 primary implantations per year. METHODS AND RESULTS: In 2001, 12 centres out of a total of 49 performed less than 50 primary implantations per year, representing 5% of the total regional activity, which was estimated to be 6414 procedures. The remaining 95% of procedures were spread evenly among 8 high-throughput centres (> 200 primary implantations per year) and 29 medium-throughput centres (50 to 200 primary implantations per year). Indications for pacing were analysed retrospectively by a team of regulatory doctors on a sample of 2176 patients with reference to the ACC/AHA/NASPE guidelines. After examination of the medical records, the indication was ranked as being class I, II or Ill (absence of indication). A valid indication was lacking in 8.2% of cases. Sinus node dysfunction represented 74.6% of the non-indications, and this classification had the predictive factors of asymptomatic dysfunction, and treatment with anti-arrhythmic or bradycardic medication. The proportion of class III interventions was significantly lower in the high-throughput centres (5.8 vs 9.9%, p < 0.05). CONCLUSION: 8.2% of primary pacing procedures were not indicated and resulted principally from asymptomatic sinus node dysfunction.

[Arrhythmogenic right ventricular dysplasia and sudden cardiac death]. / Dysplasie ventriculaire droite arythmogène et mort subite.

ARVD manifests itself by a wide spectrum of clinical presentations from asymptomatic patients to a broad range of ventricular arrhythmia, extrasystoles, tachycardia, or sudden arrhythmic death which can be the first symptom. It is a major cause for sudden death in young people and sportsmen. In known ARVD the risk of sudden death is not easy to assess from the literature, as its natural history is modulated by the wide variety of antiarrhythmic therapies. Hemodynamically ill tolerated ventricular arrhythmia, left ventricular involvement, sports, a youger age below 35, and uncontrolled therapy seem to predict an adverse outcome for these patients. These data may be helpful to decide for an AICD.

[Effects of 50 to 60 Hz and of 20 to 50 kHz magnetic fields on the operation of implanted cardiac pacemakers]. / Effets des champs magnétiques de 50 et 60 Hz et de 20 à 50 kHz sur le fonctionnement des cardiostimulateurs implantés.

UNLABELLED: The effect of 50 Hz and 60 Hz (frequencies of current distribution) and 20 kHz to 50 kHz (frequencies of induction cooktop) magnetic interference on implanted pacemakers have been assessed with the present generation of device technology. Sixty patients implanted in 1998 and 1999 with dual chamber pacemakers from 9 different manufacturers were monitored with telemetry while passing through, and standing between a system of two coils. They generated a 50 Hz or a 60 Hz magnetic field at 50 microT. Then, patients used a cooktop at different power. The recordings were made with the standard setting of "medically correct" sensing parameters chosen for the patients. Then pacemakers were reprogrammed to the unipolar mode, with the highest atrial (A) and ventricular (V) sensitivity that did not induce muscular inhibition while moving. Between each exposure (50 Hz, 60 Hz or 20 kHz to 50 kHz), the pacemaker programmation was controlled. At the end of the tests, pacemakers will be reprogrammed with the standard setting. The medical observer being blind to the existence or not of the magnetic field. No pacemaker was influenced by the vicinity of the magnetic field at medically correct settings. At unipolar high sensitivity, no inhibition nor reprogramming was observed. Transient reversion to interference mode was observed in 6 cases, 3 transient acceleration due to atrial detection of the interference, and one T wave detection by the ventricular lead. All were observed with the 60 Hz, and only 3 with the 50 Hz magnetic field. One device (Biotronik) shifted out of its special program (hysteresis research) during the tests with the induction cooktop, but it maintained its standard program, and the event could not be repeated despite further testing. CONCLUSION: Actual pacemakers do not present any electromagnetic interference with 50 Hz and 60 Hz or induction cooktop frequency working. They are insensitive with medically correct settings. Unusual high sensitivity leads only to noise reversion mode, or transient ventricular tracking.

[Cardiac Pacemakers, implantable defibrillators and IRM]. / Stimulateurs cardiaques, défibrillateurs implantables et IRM.

The IRM is formally contraindicated to the pacemaker and cardiac defibrillator wearers because of the risk of inhibition or inappropriate stimulations during the examination. However if the examination is essential, suitable programming of the apparatus and a constant monitoring of the heartbeat rate by a qualified doctor in cardiac stimulation must make it possible to avoid any accident.

[Effect of external electrical interference on pacemakers]. / L'effet des interférences électriques externes sur les stimulateurs cardiaques.

Cardiac pacemaker are sensitive to many kind of electromagnetic interference (EMI). However the low rate of reported effects is due to many protective features. Risks are minimal in everyday life conditions as airport detectors, electronic anti-thief systems, domestic electrical appliances and even mobile phones with the most recent models. Interference detection can be prevented by "medically correct" setting, with the use of bipolar sensing, and ventricular sensitivity above 2 mV. The effect of EMI from the industrial world are difficult to assess and need an individual study. The most important risks occur in the medical world, with the electrocutary, thransthoracic DC shocks, and magnetic resonance imaging.

Enalapril improves arterial elastic properties in rats with myocardial infarction.

Systemic arterial elastic properties, important determinants of left ventricular function and coronary blood flow, are compromised in myocardial infarction (MI). The cardiac effect of angiotensin-converting enzyme inhibitors (ACEIs) has been extensively studied, whereas their arterial effect has been poorly reported in MI. The aim of this work was to study the effect of prolonged ACEI enalapril treatment on systemic arterial structure and elastic properties in rats with MI. One week after the induction of an MI, 40 male Wistar rats received either no treatment (n = 20) or ACEI enalapril (2 mg/kg; n = 20) for 17 weeks. At the end of the treatment period, blood pressure, cardiac output, total peripheral resistance, systemic arterial compliance, characteristic impedance, and left ventricular power were measured in anesthetized rats. Then the rats were killed for infarct-size determination and aortic histomorphometric study. Infarct size, heart, and left and right ventricular weights were similar in the ACEI-treated and untreated infarcted rats. Prolonged ACEI enalapril treatment reduced blood pressure by 17% (p < 0.001), total peripheral resistance by 22% (p < 0.01), and characteristic impedance by 26% (p < 0.03), and increased systemic arterial compliance by 35% (p < 0.01), in comparison with untreated infarcted rats. Enalapril reduced aortic media wall thickness by 9% (p < 0.02) and increased elastin content by 22% (p < 0.03) and elastin-to-collagen content ratio by 42% (p < 0.01). Enalapril did not affect cardiac output and left ventricular power. Smooth muscle cell nuclei number and size and collagen content of aortic wall were similar in the ACEI-treated and untreated infarcted rats. These results indicate that long-term treatment with ACEI enalapril improves arterial elastic properties through structural modifications of arterial wall in rats with MI. This vascular effect may contribute to improve the left ventricular function and the coronary perfusion of infarcted myocardium, and added to the cardiac effect, may explain the prevention of left ventricular remodeling observed with ACEI in this model.

[Combination of celiprolol and amiodarone in the treatment of recurrent ventricular tachycardia]. / L'association du céliprolol à l'amiodarone dans le traitement des tachycardies ventriculaires récidivantes.

The combination of beta-blockers and amiodarone has been shown to be affective in the treatment of refractory chronic ventricular tachycardia. However, the possible induction of excessive sinus bradycardia can constitute a limitation to the use of this treatment. Celiprolol is a cardioselective beta-blocker with a partial beta-2 agonist activity and an alpha-2 blocking activity, with a minimal depressant effect on heart rate. It therefore seemed useful to evaluate this drug in combination with amiodarone in patients with chronic ventricular tachycardia refractory to amiodarone alone. Twelve men with age of 57 +/- 16 years (9 with a history of myocardial infarction) received 200 mg of celiprolol per day associated with an average of 2 grams of amiodarone per week. Failure of oral amiodarone alone was confirmed by "reloading" (1,200 mg per day for 4 days) in 11 patients. The mean left ventricular ejection fraction was 36 +/- 19%, and was < or = 30% in 5 patients. Three patients were classified as stage 3-4 of the NYHA functional classification. Episodes of tachycardia were paroxysmal in 10 patients and diurnal in 10 cases. The effects of treatment were evaluated by clinical examination, continuous electrocardiographic monitoring, stress test and endocavitary electrophysiological investigation. No patient developed cardiac decompensation or collapse during beta-blocker treatment. In one case, the dose of celiprolol had to be decreased to 100 mg per day because of hypotension. No proarrhythmic effect was observed. The sinus rate remained unchanged after addition of celiprolol to amiodarone (57 +/- 3 bpm before versus 56 +/- 4 bpm after). On the stress test, the exercise capacity was maintained and no tachyarrhythmia was induced. Right ventricular refractory periods were not modified by celiprolol (mean effective period 289 +/- 20 ms before versus 294 +/- 20 ms after). Following a hospital stay of 17 +/- 7 days, the beta-blocker was discontinued in 5 patients because of persistence of permanent tachycardia in 1 case, and because of inducibility of a tachycardia with the same frequency as before treatment in the other 4 cases. No sudden death or haemodynamically unstable recurrence of ventricular tachycardia were observed during follow-up over a period of 38 +/- 24 months (range: 2-55) of the 7 patients in whom treatment was considered to be effective. Only one patient presented a temporary and reversible deterioration of heart failure. The absence of excessive bradycardia was also observed during follow-up. In one patient, celiprolol was replaced by another antiarrhythmic due to the recrudescence of inducibility to programmed stimulation. Three patients developed a spontaneous recurrence of sustained monomorphie ventricular tachycardia, which was well tolerated. In conclusion, these results suggest that celiprolol in combination with amiodarone in the treatment of refractory chronic ventricular tachycardia is a valuable therapeutic option because of its good inotropic and particularly chronotropic safety. However, the efficacy of treatment must be evaluated by a stress test and by endocavitary electrophysiological investigation including programmed ventricular stimulation in every case.

[Outcome of arrhythmogenic right ventricular dysplasia. Apropos of 4 cases]. / Modalités évolutives de la dysplasie ventriculaire droite arythmogène. A propos de 4 observations.

The authors propose a classification of the outcome of arrhythmogenic right ventricular dysplasia with reference to 4 selected cases with a follow-up period of over 9 years. In type I, the left ventricular ejection fraction is normal (EF > 50%) and the risk, exclusively arrhythmic, can be controlled by appropriate antiarrhythmic therapy. This is the commonest form of arrhythmogenic right ventricular dysplasia with different varieties according to the degree of dilatation of the right ventricle. In type II, there is a variable degree of left ventricular involvement (30 < EF < 50%) either by extension of a comparable disease process as observed in the right ventricle or by an isolated or superimposed phenomenon of myocarditis. This form is stable and may remain stable for many years providing the arrhythmias are correctly treated. In type III, progressive degradation of the myocardium is observed over a period of about 10 years with a clinical presentation comparable to that of certain arrhythmogenic dilated cardiomyopathies which are often hereditary. In this case, the patients have an arrhythmic risk associated with that of cardiac failure which becomes progressively irreversible. The histology shows interstitial fibrosis with biventricular lymphocytic infiltration suggesting an autoimmune phenomenon. Therefore, the classification of cases of arrhythmogenic right ventricular dysplasia depends on the potential evolutivity of the lesions. When the patient is seen in the early stages of the disease, the prognosis should be garded, especially in a hereditary form.

[Value and limitations of diagnostic function of bradycardia of a ventricular pacemaker]. / Intérêts et limites de la fonction diagnostique de bradycardie d'un stimulateur ventriculaire. Groupe d'étude du registre Théorema.

The indication for permanent pacing may be confirmed by a bradycardia counter in patients without ECG or Holter recording of the causal bradycardia. The algorithm was assessed in a multicenter register with the SORIN Theorema model. The activation of the device was programmed on a double hysteresis of 2 seconds with a programmable histogramme of detections and sensing and pacing counters. One hundred and forty five patients were recruited in 50 centers over 2 years: 89 men and 56 women aged 33 to 96 years (average 72 years), 87 of whom had no other obvious cardiac disease. One hundred and ten had typical syncopal episodes, 19 had atypical or minor syncopal attacks and 16 were asymptomatic, one with sinus node dysfunction and the others with pathological prolongation of the HV interval (> or = 70 ms) during endocavitary electrophysiological investigation. The mechanism of the bradycardia was considered to be infra-hisian in 62 patients who had HV intervals > or = 70 ms. This was also the probable mechanism in 20 others who had bundle branch block and typical syncope despite a HV interval < 70 ms and in 6 patients with bundle branch block and typical syncope who did not undergo electrophysiological investigation before implantation. Twenty one patients had sinus node dysfunction during electrophysiological investigation and 8 had a carotid sinus syndrome. The remaining 28 cases had transient syncope but no ECG changes or abnormality on electrophysiological investigation. Permanent pacing was proposed when an extracardiac origin of the syncope was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-pharmacological methods of treatment of tachycardia]. / Méthodes non pharmacologiques de traitement des tachycardies.

Anti-tachycardia drugs have the advantage of preventing recurrent arrhythmia in most cases but have the disadvantage of requiring long-term prescriptions and producing extra-cardiac and cardiac side effects. In addition, paradoxical arrhythmogenic effects sometimes occur. With the advent of radiofrequency catheter ablation and implantable defibrillators, a whole new range of indications for non-drug treatments suddenly became possible. Radiofrequency ablation is now a real alternative in cases of Wolff-Parkinson-White junctional tachycardia with intranodal re-entry and accessory pathways since the success rate is 95%. For atrial flutter and ventricular tachycardia, myocardial localizations of the causal lesions are more diffuse and the clinical success rate is lower. Consequently, since other arrhythmias may occur, ablative treatment is usually reserved for drug-resistant cases. An implantable defibrillator is the only treatment, with the exception of cases with an identifiable acute origin, for ventricular fibrillation. In many countries, defibrillators are also implanted for drug-resistant ventricular tachycardia.

Diagnosis of ventricular tachycardia using a pacemaker Holter function.

The diagnosis of ventricular tachycardia (VT) using the Holter function of an implanted pacemaker has not yet been reported. We present the case of a patient with episodes of slow VT, hemodynamically stable, but in whom long lasting attacks were not identified by the patient as VT recurrences, finally leading to progressive heart failure. Prospective analysis of the 24-hour ECG and comparison with the pacemaker Holter data allowed us to determine diagnostic criteria to recognize VT using the pacemaker Holter function. Using these criteria it was possible to retrospectively diagnose VT occurrence during the weeks when the patient was out-of-hospital.

[The radiofrequency and the elimination of accessory atrioventricular pathways. The factors related to successful transcatheter ablation]. / Radiofrecuencia y eliminación de vías accesorias atrio-ventriculares. Factores relacionados con ablación exitosa trans-catéter.

Some factors related with successful radiofrequency catheter ablation were retrospectively analyzed from the initial patients with WPW syndrome that underwent this therapy. They were 21 patients, and success rate with radiofrequency therapy was 73%. Conventional conduction intervals were obtained from catheter ablation electrograms. Only ventricular activation around Delta-wave onset, and earliest retrograde atrial activation were statistically significant for successful ablation (P < 0.05 both). Inadvertent interruption of AV-His bundle was produced ablating a septal accessory pathway, and no mortality procedure-related was observed. We conclude that radiofrequency catheter ablation of accessory pathways represents nowadays, an effective solution in patients with symptomatic arrhythmias, besides its high success rate and low risks, but different mapping criteria should be considered to attain an efficient elimination of atrioventricular accessory-pathways.

[Ventricular tachycardia in a patient with rate-responsive cardiac pacemaker]. / Tachycardie ventriculaire chez un porteur de stimulateur cardiaque à fréquence asservie.

The authors report a case of syncopal ventricular tachycardia in a patient with a respiratory-dependent rate responsive pacemaker, followed-up for valvular heart disease with severe left ventricular dysfunction and sustained atrial and ventricular arrhythmias. The introduction of low dose betablocker therapy with reinforcement of the treatment of cardiac failure controlled the ventricular arrhythmia, after suppression of the data responsive function had been shown to be ineffective. The authors discuss the role of the rate responsive function in the triggering of the ventricular tachycardias.

[Acute hemodynamic effects of SIN-1 and isosorbide dinitrate in stable left ventricular failure: a comparative double-blind, cross-over study]. / Effets hémodynamiques aigus du SIN-1 et du dinitrate d'isosorbide dans l'insuffisance ventriculaire gauche stable: etude comparative randomisée en double aveugle et cross-over.

The acute hemodynamic effects of intravenous SIN-1 (1 mg) and sublingual isosorbide dinitrate (5 mg) were investigated in 12 patients (8 men and 4 women) between 38 and 80 years of age and suffering from stable chronic left ventricular failure (NYHA Classes III-IV) secondary to ischemic myocardiopathy (n = 5), hypertensive disease (n = 2) or idiopathic disorder (n = 5) corresponding to the following hemodynamic inclusion criteria: stable condition, cardiac index > or = 2 l/min/m2, mean capillary pressure > or = 18 mmHg and < or = 28 mmHg. Previous treatments were continued with the exception of vasodilators and diuretics which were stopped 24 hours earlier. The hemodynamic data from this cross-over, double-blind double-dummy trial were collected for two 60-hour periods separated by a washout period of 120 minutes. Simultaneously, venous samples were taken for the assay of plasma levels of SIN-1. The heart rate, cardiac output, pulmonary artery resistance and blood pressure were not affected by either SIN-1 or isosorbide dinitrate. An obvious reduction (> 15% of the basal value) in the mean capillary pressure, pulmonary artery pressure and mean right atrial pressure was observed in 10 subjects after SIN-1 and in 7 patients isosorbide dinitrate. A statistically non-significant trend towards a more marked effect (number of patients responding and maximum amplitude of pressure reduction) which occurred more rapidly and lasted longer was observed after SIN-1. Analysis of the relationship between the pharmacodynamics and pharmacokinetics of SIN-1 suggests that an active metabolites is involved. No adverse effects were reported.(ABSTRACT TRUNCATED AT 250 WORDS)

[Right ventricular dysplasia]. / La dysplasie ventriculaire droite.

Arrhythmogenic right ventricular dysplasia is responsible for ventricular tachycardia affecting an apparently healthy heart. It can sometimes lead to sudden death, which may be the presenting symptomatology of the disease. It results from fibro-adipose infiltration of the free wall of the right ventricle, and sometimes of the septum, possibly secondary to myocarditis. The prognosis depends upon the quality of the left ventricle. If it is healthy, the only risk is that of arrhythmia. Treatment using anti-arrhythmic drugs is most often effective and, with proper management, the prognosis is good and the risk of sudden death eliminated. If the left ventricle is abnormal, there is the risk that dysplasia associated with arrhythmia will progress to right then congestive cardiac failure in the context of a dilated idiopathic cardiomyopathy with ventricular tachycardias originating on the right side. Arrhythmogenic right ventricular dysplasia is a notable cause of sudden death in athletes. Routine screening of such individuals is justified, as is that of those with high risk occupations (locomotive and vehicle drivers, etc.).