Anti-arrhythmic effects of I (Na), I (Kr), and combined I (Kr)-I (CaL) blockade in an experimental model of acute stretch-related atrial fibrillation.

INTRODUCTION: Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications for anti-arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated the electrophysiological effects of three different anti-arrhythmic drugs: dofetilide, flecainide and BRL-32872 (associating I (Kr) and I (CaL) blocking properties). METHODS: After 30 min of sustained stretch-related AF, we perfused BRL 10-7 M, BRL 3.10-7 M, BRL 10-6 M, flecainide 2.4 10-6 M and dofetilide 10-7 M and iteratively measured atrial effective refractory periods (ERPs), AF inducibility and AF cycle length (AFCL) 15, 30 and 60 min after drug perfusion, respectively. RESULTS: After a significant shortening of the ERPs by acute atrial stretch in the five groups individually (p < 0.001, stretch vs baseline for each group individually), drug perfusion led to a strong lengthening of AFCL, a very significant prolongation of ERPs (p < 0.001 vs stretch) and a reduction of AF inducibility (p < 0.01 vs control group) for each of the five experimental groups. The relative ERP increase was comparable in all groups, whereas a significantly lower AF inducibility was observed in the BRL 10-6 M group (p < 0.05 vs other BRL concentrations). CONCLUSION: In a model of acute stretch-related AF, dofetilide, flecainide and BRL-32872 terminated AF and prevented its immediate reinduction after having comparatively prolonged AFCL and ERPs. These comparative results suggest that those drugs are equally efficacious, albeit with different mechanisms, in the setting of acute atrial stretch.

[Buerger's disease and coronary disease]. / Maladie de Buerger et atteinte coronaire.

The authors report the case of a 33 year old man with distal occlusive arterial disease diagnosed as Buerger's disease, with two previous transient ischaemic attacks and coronary disease resulting in myocardial infarction. Coronary angiography showed narrowing of the second segment of the left anterior descending artery, occluded distally and not suitable for revascularisation. The observation of coronary artery disease is very rare in Buerger's disease and data of coronary angiography are very sparse in this context. The occurrence of myocardial infarction and the angiographic appearances of the left anterior descending artery raise the question of coronary involvement of Buerger's disease.

Predictive factors of ventricular fibrillation triggered by pause-dependent torsades de pointes associated with acquired long QT interval: role of QT dispersion and left ventricular function.

INTRODUCTION: Death due to acquired torsades de pointes usually is caused by ventricular fibrillation (VF), but the contributing factors to VF triggered by pause-dependent torsades de pointes are not understood. METHODS AND RESULTS: We evaluated 91 patients who fulfilled four criteria: (1) pause-dependent torsades de pointes; (2) prolonged QT interval and/or corrected QT (QTc) (>0.44 sec); (3) long-short initiation sequence; and (4) conditions known to induce pause-dependent torsades de pointes. There were 38 patients with a documented VF (group I) and 53 without VF (group II). Absolute and relative dispersions of QT and QTc were calculated based on the 12-lead standard ECG. Group I differed from group II with regard to myocardial infarction history (32% vs 13%; P = 0.035), left ventricular ejection fraction (44% +/- 14% vs 65% +/- 9%; P < 0.0001), presence of structural heart disease (100% vs 20.8%; P < 0.0001), QT mean (591 +/- 73 msec vs 514 +/- 78 msec; P < 0.0001), QTc mean (563 +/- 76 msec vs 508 +/- 90 msec; P = 0.002), absolute QT dispersion (166 +/- 56 msec vs 84 +/- 49 msec; P < 0.0001), relative QT dispersion (9.9% +/- 3.5% vs 6.3% +/- 3.2%; P < 0.0001), absolute QTc dispersion (158 +/- 57 msec vs 81 +/- 44 msec; P < 0.0001), and relative QTc dispersion (9.9% +/- 3.6% vs 6.2% +/- 3%; P < 0.0001). Multiple regression analysis showed that ejection fraction (P = 0.0001), presence of structural heart disease (P < 0.0001), and relative QTc dispersion (P = 0.038) were the only independent predictors of VF. CONCLUSION: Left ventricular function, presence of structural heart disease, and QTc relative dispersion should be evaluated carefully in patients with conditions susceptible to inducing torsades de pointes.

[Hospital management of atrial fibrillation. Epidemiologic data and therapeutic strategy. Report of 100 consecutive patients]. / Prise en charge hospitalière de la fibrillation auriculaire. Données épidémiologiques et stratégie thérapeutique. A propos de 100 patients consécutifs.

Despite recent large scale trials, the management of atrial fibrillation remains very variable. The authors report the results of a prospective study of the management of atrial fibrillation in their department. One hundred consecutive patients admitted for atrial fibrillation were included in the study. The epidemiological and clinical data and the results of the therapeutic strategy were recorded prospectively. Three embolic complications occurred before hospital admission. The hospital stay was marked by spontaneous reduction of atrial fibrillation in 14 cases in the 6 hours following admission. The therapeutic strategy was the following: 40 arrhythmias were respected (well tolerated, > 1 year or with a left atrium 60 mm). Oral amiodarone (30 mg/Kg and 15 mg/Kg the next day) was given to 22 patients. Only 9 patients (41%) were converted (average delay of 12 hours). Four patients received intravenous amiodarone, reducing two arrhythmias. Twenty patients were treated by external electrical cardioversion of first intent and 14 after failure of pharmacological reduction. All of these procedures, early (after 48 hours anticoagulation and transoesophageal echocardiography), or late (after 1 month of anticoagulation), restored sinus rhythm without complications, especially embolic. This register showed a relatively low efficacy of oral amiodarone in the reduction of atrial fibrillation and underlines the efficacy and safety of external electrical cardioversion, even when performed early.

His-Purkinje system reentry as a proarrhythmic effect of flecainide.

We report a case of tachycardia due to reentry within the His-Purkinje system (HPS) occurring after introduction of flecainide. The patient presented with a mild mitral regurgitation and normal left ventricular function. He had incomplete left bundle branch block with left-axis deviation. At the electrophysiology study, a prolonged HV interval was observed at baseline, and the tachycardia could be reproduced after ajmaline infusion. Six months after interruption of flecainide, the patient remains free of arrhythmia recurrence. The authors emphasize that proarrhythmic effects of flecainide may include reentry within the HPS in patients with underlying HPS disease.

Continuous monitoring of an endocardial index of myocardial contractility during head-up tilt test.

BACKGROUND: Previous studies suggest that vigorous myocardial contractions stimulate ventricular mechanoreceptors and lead to vasovagal syncope. We studied an endocardial index of myocardial contractility during the head-up tilt test in vasovagal patients and control patients, and we evaluated the effect of negative inotropic drugs on myocardial contractility and tilt test outcome. METHODS AND RESULTS: We investigated 19 patients with recurrent vasovagal syncope and positive tilt test (group 1) and 11 patients with no syncope and negative tilt test (group 2). Myocardial contractility was continuously measured during a tilt test (60 degrees ) through a microaccelerometer incorporated in the tip of a right ventricular electrode to sense left ventricular contractility. Patients in groups 1 and 2 were evaluated during an unmedicated tilt test, and patients in group 1 were reevaluated during a tilt test with infusion of esmolol (n = 10) or disopyramide (n = 9). During the unmedicated test, patients in group 1 exhibited a significant increase in myocardial contractility immediately on postural change (P <.05), unlike patients in group 2. Patients in group 1 also had a further increase in myocardial contractility before the end of tilt (P <.01). With drug administration, the changes in supine myocardial contractility were nonsignificant and were not related with the outcome of the tilt test (P <.05). CONCLUSIONS: An increase in myocardial contractility is detected by the sensor during the tilt test. The changes induced by the drugs on supine myocardial contractility are minor and not related with the outcome of the head-up tilt test.

Near fatal electrical storm in a patient equipped with an implantable cardioverter defibrillator for Brugada syndrome.

A patient with Brugada syndrome experienced incessant ventricular fibrillation 7 years after implantation of an ICD. General anesthesia, fast ventricular pacing, bretylium, and atenolol infusion were ineffective; amiodarone infusion was started. After 190 defibrillation shocks over 36 hours, the electrical storm stopped. A multiorgan failure occurred as a complication of the electrical storm and necessitated prolonged reanimation. Thorough cardiac evaluation revealed no structural abnormality and the patient, now on chronic oral amiodarone therapy, remains free of arrhythmia 1 year after the event.

Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

UNLABELLED: Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct human hereditary cardiac diseases known to cause ventricular tachyarrhythmias (torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death. OBJECTIVE: In this study we have identified and electrophysiologically characterized, in patients having either LQTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene). METHOD: The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique. RESULTS: The R1512W mutation found in our first patient diagnosed with Brugada syndrome produced a slowing of both inactivation and recovery from inactivation. The R4132G mutation found in our second patient who also presented Brugada syndrome, resulted in no measurable sodium currents. Both Brugada syndrome patients showed ST segment elevation and right bundle-branch block, and had experienced syncopes. The E1784K mutation found in the LQTS showed a persistent inward sodium current, a hyperpolarized shift of the steady-sate inactivation and a faster recovery from inactivation. CONCLUSION: The different clinical manifestations of these three mutations most probably originate from the distinct electrophysiological abnormalities of the mutant cardiac sodium channels reported in this study.

[Pacemaker syndromes]. / Les syndromes du pacemaker.

The pacemaker syndrome refers to symptoms and signs in pacemaker patients caused by inadequate timing of atrial and ventricular contractions. The lack of normal atrioventricular synchrony may result in decreased cardiac output and increased in atrial pressure which elicits a systemic hypotensive reflex response. These hemodynamic disturbances mostly occur in the presence of retrograde VA conduction is present. The incidence of pacemaker syndrome is uncertain, and varies from 7% to 20% of all ventricular paced patients. Neurologic symptoms or symptoms suggesting low cardiac output or congestive heart failure are indicative of the pacemaker syndrome. These symptoms may vary from mild to severe, they are nonspecific and very common among cardiac patients with or without pacemaker. In many patients they are not even noted until AV synchrony is restored. The pacemaker syndrome is not restricted to the VVI stimulation mode. It can be seen, though rarely, in atrial and even dual-chamber pacing (VDD, DDI, DDD). In these cases it is usually occasional and may be due to inappropriate programming or selection of the pacing mode.

Prolonged QT interval and altered QT/RR relation early after radiofrequency ablation of the atrioventricular junction.

This study evaluated the paced QT interval in the days after radiofrequency ablation of the atrioventricular junction in patients with chronic rapid atrial fibrillation. There is an abnormality in the dynamics of the paced QT interval until the second day after ablation, resulting in an increased duration when the paced heart rate is <75 beats/min.

[Infections secondary to implantation of cardiac pacemakers]. / Infections secondaires à l'implantation d'un stimulateur cardiaque.

Infectious complications of pacemaker implantation are not common but may be particularly severe. Localised wound infections at the site of implantation have been reported in 0.5% of cases in the most recent series with an average of about 2%. The incidence of septicaemia and infectious endocarditis is lower, about 0.5% of cases. The operator's experience, the duration of the procedure and repeat procedures are considered to be predisposing factors. The main cause of these infections is though to be local contamination during the implantation. The commonest causal organism is the staphylococcus (75 to 92%), the staphylococcus aureus being the cause of acute infections whereas the staphylococcus epidermis is associated with cases of secondary infection. The usual clinical presentation is infection at the site of the pacemaker but other forms such as abscess, endocarditis, rejection of the implanted material, septic emboli and septic phlebitis have been described. The diagnosis is confirmed by local and systemic biological investigations and by echocardiography (especially transoesophageal echocardiography) in cases of right heart endocarditis. There are two axes of treatment: bactericidal double antibiotherapy and surgical ablation of the infected material either percutaneously or by cardiotomy. Though controversial, and unsupported by scientific evidence, the role of systematic, preoperative, prophylactic antibiotic therapy in the prevention of these complications seems to be increasing.

Safety and tolerability of intravenous cibenzoline for acute termination of spontaneous sustained ventricular tachycardia. Cibenzoline and spontaneous VT.

STUDY OBJECTIVES: To evaluate prospectively, the tolerability and safety of intravenous cibenzoline therapy, for the cardioversion of spontaneous monomorphic ventricular tachycardia (VT). SETTING AND PATIENTS: Between February 1990 and December 1996, fifty-eight patients aged 59+/-10 years old (fifty-three males, five females), with spontaneous VT not causing cardiac arrest, received intravenous cibenzoline. Their underlying heart conditions were: ischemic heart disease [35], dilated cardiomyopathy [14], right ventricular dysplasia [3], hypertrophic cardiomyopathy [1], valvulopathy [2], Fallot's Tetralogy [1] and primary arrhythmogenic disease [2]. The left ventricular ejection fraction was 42+/-13% (range 20%-76%). RESULTS: The mean dose of cibenzoline was 70+/-12 mg. The tachycardia stopped within 6+/-3 min in 47 (81%) patients. Side effects from cibenzoline occurred in two patients. The hemodynamic complications were limited to hypotension, that required vasopressor therapy in one patient. The only apparent proarrhythmic effect consisted of an isolated change in the morphology of the VT, that resolved spontaneously on withdrawal of the drug. No mortality occurred at the hospital. CONCLUSION: With appropriate rules for its administration, intravenous cibenzoline has the potential to become one of the first-line antiarrhythmic drugs, to be used for cardioversion of patients with spontaneous VT.

A sensor-based evaluation of heart contractility in patients with head-up tilt-induced syncope.

Studies using the head-up tilt test (HUT) suggest that a reflex increase in sympathetic activity resulting in vigorous myocardial contractions precedes neurally-mediated syncope (NMS). The aim of this study was to evaluate heart contractility changes during positive HUT. Ten patients with recurrent NMS and positive HUT were investigated. Before HUT we temporarily placed a standard right ventricular pacing electrode incorporating in its tip a recently developed microaccelerometer (Sorin Biomedica, Italy) that measures the peak endocardial acceleration (PEA) during the isovolumetric phase as an index of heart contractility. PEA potential amplitude, heart rate and mean blood pressure were continuously studied during HUT. Syncope occurred 16.7 +/- 10.3 min after 60 degrees tilt, either at baseline (8 patients) or after sublingual nitrate administration (2 patients). PEA value was stable at 0.62 +/- 0.34 (1G = 9.8 m/sec2) during the supine phase. It slightly increased to 0.72 +/- 0.44 G (p = NS) during the first minutes of 60 degrees tilt and then remained unchanged until a further increase of 71 +/- 79% (range 10 to 266%) as compared to tilt value (p = 0.004) at 2.8 +/- 2.4 min (range 0.25 to 6.5 min) before the syncope in 9 patients. The latter increase was not observed in the patient with dilated cardiomyopathy. In conclusion, a significant increase in heart contractility was observed in 9 patients in the minutes preceding HUT-induced NMS. These changes might be used for driving a rate adaptive pacemaker when cardiac pacing is indicated to prevent NMS.

Arrhythmic cardiac arrest due to isolated coronary artery spasm: long-term outcome of seven resuscitated patients.

OBJECTIVES: Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm. BACKGROUND: Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone. METHODS: The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result. RESULTS: The patients' mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm. CONCLUSIONS: A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.

Treatment of malignant primary vasodepressive neurocardiogenic syncope with a rate responsive pacemaker driven by heart contractility.

In a 41-year-old man suffering from frequent syncope, the tilt test reproducibly induced a primary vasodepressive neurocardiogenic syncope. Pharmacotherapy either failed to prevent the syncope induced at the tilt test or was poorly tolerated. In the minutes preceding the syncope, a dramatic increase in heart contractility was sensed by a microaccelerometer located at the tip of a right ventricular pacing electrode. When the tilt test was repeated with the pacemaker programmed in the DDDR mode, high rate dual chamber pacing occurred during the tilt phase and prevented the syncope. Three months after implantation, the patient remains totally symptom free.

A complication of pacemaker lead extraction: paradoxical embolism of a lead fragment in a leg artery.

Extraction of three chronically implanted pacemaker leads was performed via the implant vein in a 71-year-old man. One of the leads broke in the subclavian scar tissue. The lead fragment migrated into the left peroneotibial trunk artery. Transesophageal echocardiography showed patent foramen ovale associated with right-to-left atrial shunt. This complication of lead extraction is discussed along with the role of echocardiography prior to lead removal.