Exclusion of HRAS from long QT locus.
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Chromosome Mapping↗
Biomedical subjects
P Coumel
Publications and source records attributed to P Coumel.
Paroxysmal atrial fibrillation: a disorder of autonomic tone?
Electrophysiological characteristics of atrial cells (action potential duration and refractoriness, conduction speed) are modulated differently by vagal and sympathetic influences. The former tends to favour macro-reentry phenomena whereas the latter favours abnormal automaticity and triggered activity. In normal hearts vagal influences are predominant, thus explaining that the clinical pattern of vagal-mediated paroxysmal atrial fibrillation is preferentially observed in the absence of detectable heart disease, in young male adults, with an ECG pattern of common flutter alternating with fibrillation. Symathetically mediated atrial fibrillation is observed in the presence of any heart disease, the first effect of which is to provoke a vagal withdrawal. The clinical history is a reliable guide for suspecting which type of physiological autonomic predominance contributes to destabilize the arrhythmogenic substrate, but observing the behaviour of sinus rate variability just preceding the onset of the arrhythmia only permits documentation of the mechanism. The role of the autonomic influences should be taken into consideration every time conventional antiarrhythmic treatment is insufficient. Beta-blockers as well as digitalis may be either beneficial or detrimental, according to the causal mechanism, so that the choice of their use as a single or a combined therapy should be appropriate.
Adult↗
Phenotypic determinants of heart rate variability in cardiac hypertrophy and failure.
Reduced heart rate variability (HRV) has a strong predictive value in terms of sudden death, as compared to other prognostic criteria, but it has never been previously studied in experimental models of cardiac hypertrophy and failure. However, it has been quantified in rats using Holter monitoring and the peak and trough method of analysis. In normal rats, as in humans, short and long oscillations, sensitive, respectively, to atropine and propranolol were detected. Both correlate with heart rate. Cardiothyrotoxicosis was characterized by tachycardia and, independently, by a pronounced alteration in long oscillations. HRV was normal in compensatory cardiac hypertrophy due to aortic stenosis, but in this model the normal correlation existing between HRV and heart rate had disappeared. It is suggested that the main determinants of the above modifications of HRV are the changes in the new myocardial phenotype observed in terms of beta-adrenoceptor and muscarinic densities.
Animals↗
Idiopathic verapamil-responsive left ventricular tachycardia: clinical characteristics and long-term follow-up of 33 patients.
Long-term prognosis, pharmacological prophylaxis and transcatheter ablation in a large group of patients with idiopathic verapamil-responsive left ventricular tachycardia (IVRLVT) are reported in this study. Thirty-three patients with a mean age of 27 +/- 16 years at their first IVRLVT episode, were studied retrospectively. Ventricular tachycardia was of the right bundle branch block morphology in all cases, with left axis deviation in 29 and right axis deviation in five (one patient had the two morphologies). Mitral valve prolapse was present in four patients; no heart disease was found in the remaining 29. Ventricular tachycardia could be electrophysiologically induced in 90% of the patients; Holter monitoring showed only sporadic ventricular extrasystoles in 76%; late potentials were found in 33% of the cases. At the end of a follow-up of 5.7 +/- 4.7 years, no patient had died. Thirty-one patients (94%) received a mean of 2.5 +/- 1.2 drugs; beta-blockers were effective in 71% of the cases, verapamil in 25%, class 1 drugs in 22%, class 3 drugs in 18%. Two patients who never received prophylaxis and four in whom it was stopped, were controlled with verapamil in case of recurrence. Six patients underwent catheter ablation; two with DC shock in whom it was successful in one, and four with radiofrequency energy, with a total success rate. The good prognosis of IVRLVT has been confirmed in a long-term follow-up; a new finding is the high efficacy of beta-blockers for prophylaxis. Radiofrequency transcatheter ablation is an effective and safe therapy for patients with symptoms not controlled by drug treatment.
Adolescent↗
Exercise ECG: prognostic implications of exercise induced arrhythmias.
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Arrhythmias, Cardiac↗
Heart rate and heart rate variability in normal young adults.
INTRODUCTION: The relationships between heart rate (HR) and HR variability (HRV) are not simple. Because both depend on the autonomic nervous system (ANS), they are not independent variables. Technically, the quantification of HRV is influenced by the duration of the cardiac cycles. The complexity of these relationships does not justify ignoring HR when studying HRV, as frequently occurs. METHODS AND RESULTS: Using spectral and nonspectral methods, the HR and various normalized and non-normalized indices of HRV were studied in 24-hour recordings of a homogeneous cohort of seventeen 20-year-old healthy males. The HR-HRV relationships were appraised by analyzing the same data in two different ways. The 24 mean hourly values provide consistent information on the circadian behavior of the indices, while the average 24-hour individual data show a wide spectrum of normality. Combined approaches allow assessment of the direct impact of RR interval on HRV evaluation. The correlations between HR and normalized indices of HRV are weaker in 24-hour individual data than in pooled hourly data of the same individuals. These correlations are close to 1 in the latter case, which does not mean that measuring HRV is simply another method of evaluating HR, but that normal physiology supposes a harmonious behavior of the various indices. When considered individually without normalization, the specific indices of vagal modulation (high-frequency band of the spectrum, short-term HR oscillations of the nonspectral analysis) consistently increase at night and diminish during the day. However, the low-frequency power, which supposedly reflects sympathetic influences, also increases at night, whereas more logically the longer HR oscillations would predominate during the day. Moreover, the selective analysis of HR oscillations during HR acceleration or decrease indicates that their behavior differs accordingly. CONCLUSION: We recommend that closer attention be paid to the complex relationships between HR and HRV. The strong correlations found in healthy subjects may reflect either the physiological harmony of ANS functions or simple redundancy. Their tendency to deteriorate in diseased hearts suggests that redundancy is not the cause and that abnormalities of ANS functions are not demonstrated by HRV analysis alone.
Adult↗
Heart rate variability in two models of cardiac hypertrophy in rats in relation to the new molecular phenotype.
The analysis of heart rate variability (HRV) provides information on neural control of the heart. We investigated HRV in normal rats and in models of experimental cardiac hypertrophy using the Holter monitoring and peak/trough method. In normal rats, two heart rate oscillations with different wavelengths, high frequency (HF) and low frequency (LF) oscillations, were detected. The HF oscillations were insensitive to propranolol and suppressed by atropine. The LF oscillations were sensitive to both antagonists. Thyrotoxicosis resulted in cardiac hypertrophy (+20%) and tachycardia. The HF oscillations were unchanged, whereas LF oscillations were hampered at low heart rate in this group. Aortic stenosis resulted in cardiac hypertrophy (+53%), but heart rate oscillations were unchanged. The (number x amplitude) product for both types of oscillations correlated with heart rate in controls but not in the thyrotoxicosis or aortic stenosis models. Alterations of HRV in cardiac hypertrophy occur in rats as in humans. They may reflect the changes in the molecular components of the adrenergic/muscarinic system, which defines the new myocardial phenotype.
Analysis of Variance↗
Short-coupled variant of torsade de pointes. A new electrocardiographic entity in the spectrum of idiopathic ventricular tachyarrhythmias.
BACKGROUND: Torsade de pointes is characterized not only by its particular ECG pattern but by its context of congenital or acquired long QT syndrome and the long coupling interval of the initial premature beat. METHODS AND RESULTS: We observed 14 patients aged 34.6 +/- 10 years (mean +/- SD) with no structural heart disease who presented with syncope related to a typical ECG aspect of torsade de pointes. However, there was no evidence of long QT syndrome, and the torsade had the unusual particularity of an extremely short coupling interval of the first beat or of the isolated premature beats (245 +/- 28 milliseconds). In 10 cases they deteriorated into ventricular fibrillation. Four patients had a familial history of sudden death. Only 2 patients had a tachyarrhythmia inducible by programmed stimulation. At Holter recordings the heart rate variability was globally and significantly depressed, the vagal limb of the autonomic nervous system being predominantly affected. During a mean follow-up of 7 years there were 5 deaths (4 sudden). Nine patients are alive, 3 with implanted defibrillators and 6 treated with verapamil alone. Unlike the other types of antiarrhythmic agents including beta-blockers and amiodarone, verapamil is in our experience the only drug apparently active on the arrhythmias; however, it does not prevent sudden death. CONCLUSIONS: The short-coupled variant of torsade de pointes should be identified because of their ECG pattern and the risk of sudden death in young adults with no structural heart disease.
Adult↗
[Pericardial constriction caused by epicardial patches of automatic implantable defibrillators. Apropos of 3 cases].
The authors report three cases of pericardial constriction secondary to implantation of an automatic defibrillator. In one case, the pericardial constriction occurred 1 year after implantation and was associated with ascending infection of the patch electrodes from the stimulator; the patient died when the patch electrodes were removed, the infection having eroded the left ventricular wall. In the other two cases, signs of constriction appeared 2 years after implantation. In one of these patients, surgery showed a fibrous pericardial reaction deforming the patch electrodes with a favourable outcome when the electrodes were removed. The other patient refused surgery. In the three cases, the diagnosis was confirmed by right heart catheterisation and ventriculography which showed signs of adiastole and severe deformation of the ventricular contours. Pericardial constriction due to patch electrodes is a potentially serious complication of implantable automatic defibrillators, the prevalence of which may be underestimated. The use of endocavitary or extra-pericardial electrodes should avoid this complication.
Defibrillators, Implantable↗
[Catheter ablation of atrioventricular nodal reentrant tachycardia].
Electrophysiological data of atrioventricular nodal reentrant tachycardia recensed over the last 40 years in the animal and in man has not resolved the question as to the exact site of the reentry circuit: an exclusively intranodal pathway or a pathway involving part of the atrium? The remarkable efficacy of modern radical therapy of this arrhythmia with preservation of atrioventricular conduction reinforces the concept of reentry involving not only the atrioventricular node but also the juxta nodal atrium and the superior and inferior atrionodal connections. Radical treatment was initially surgical and then by catheter ablation. The technique of specific ablation of the rapid anterior pathway was the first to be described. Its limitation is the relatively high risk (about 10%) of complete atrioventricular block. Very quickly, radiofrequency ablation of the slow posterior pathway became the method of reference. Most patients do not have retrograde conduction in the slow pathway. The pathway is located in sinus rhythm by recording its specific potentials: either the rapid potential described by Jackman et al or the fragmented potential described by Haïssaguerre and Warin. The former is recorded from the posterior septal position anterior to the orifice of the coronary sinus; the second is recorded at the same level but slightly above in the mid septal position. Ablation of the slow pathway can be performed on these purely anatomical criteria. Using these approaches, an immediate success rate of over 90% may be obtained. The recurrence rate is 0 to 5%; that of complete atrioventricular block ranges from 0 to 4%.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Automatic implantable defibrillators: long-term results].
The automatic implantable defibrillator is an essential component of the preventive management of sudden death of patients with malignant ventricular arrhythmias. Though its efficacy in this indication is not contested, the data concerning its influence on global cardiac mortality is more controversial. The elements of this controversy are reviewed. Several prognostic factors are implicated, the principal of which being the patient's haemodynamic status as assessed by objective evaluation of left ventricular function. Prospective randomised studies comparing medical therapy with the automatic implantable defibrillator are under way and should provide a better understanding of its indications in the future.
Arrhythmias, Cardiac↗
[Right accessory pathways with slow and decremential anterograde conduction. Electrophysiological changes during ablation of the proximal atrial poles].
Right sided accessory pathways with slow and decremential anterograde conduction differ from the anatomical substrates of the nodo-ventricular connections described by Mahaim. The connection may also be atrio-ventricular or atrio-fascicular. The authors report a series of 6 patients (2 men, average age 31 +/- 9 years) with antidromic reciprocating tachycardia implicating accessory pathways with decremential conduction (wide QRS complexes with left bundle branch block) the radiofrequency ablation of which was centered on the proximal atrial pole. The increment of pre-excitation was 75 +/- 18 ms. No nodo-ventricular or nodo-fascicular connections were observed. One patient had an atrio-ventricular connection, the mapping and ablation (5 applications) of which were performed on the annulus, as if it were a bundle of Kent. Five patients had a nodo-fascicular connection which was masked during sinus rhythm. The localisation of the proximal atrial insertion on the tricuspid annulus was initially estimated by studying the superior junction of the circuit and by endocavitary stimulation, and then by recording the M potential (activation of the accessory pathway). This was recorded in 4 patients, either at a specific point on the annulus (lateral or postero-lateral) which was the target of ablation (3 patients, 5 +/- 3 applications) or over a wider region (2 cm) at which ablation failed (1 patient: 13 applications). The site of the increment was determined in 2 patients and was proximal to the M potential. The M potential could not be recorded on the annulus in one patient. In 2 patients, the M potential was also recorded along the side of the pathway on the antero-lateral wall of the right ventricle of the tricuspid valve at its distal pole. In 2 patients, ablation was centered on the distal pole in second intention, near to the terminal part of the right bundle where it was localised in one of the two (18 applications). Finally, ablation was obtained in 5 out of 6 patients. They remain asymptomatic after 12 +/- 7 months follow-up. These cases show that accessory pathways with slow decremential conduction usually behave like a complete conduction pathway with an accessory laterally situated atrioventricular node on the tricuspid, an accessory bundle and a distal insertion which are all accessible to ablation.
Adolescent↗
[Paroxysmal atrial fibrillation: role of autonomic nervous system].
The electrophysiological properties of the atrial cells (duration of action potential and refractory period, conduction speed) are differently influenced by vagal and catecholamine stimulation: the first favorising phenomena of macroreentry, the second abnormal automatism and induced activity. In the normal heart, vagal tone is dominant at atrial level explaining that the clinical entity of paroxysmal vagal atrial fibrillation is observed in the absence of detectable cardiac disease in relatively young men with ECG appearances of alternating atrial flutter and fibrillation. Catecholamine-induced atrial fibrillation is usually observed with underlying cardiac disease. Besides the clinical terrain and appearances, the observation of the circumstances surrounding the triggering of atrial fibrillation and the features of the sinus rhythm and its variability before the induction of the episodes are the main factors which demonstrate the modalities of the influence of the autonomic nervous system. In cases resistant to treatment, the knowledge of these factors provides a guide to treatment, indicating which antiarrhythmic agents are poorly adapted or even harmful.
Adult↗
[Reflections on therapeutic trials].
The approach of establishing a relationship between cause and effect is a form of research contrary to the empirism which characterises many therapeutic trials. This empirism may result in certain embarrassing situations when the criteria of evaluation do not turn out to have the value that simple correlations attribute to them. Evaluating the efficacy of a drug whilst ignoring its mechanisms of action is courting danger, especially that of being unable to pursue a line of research when the global results are known in advance. These phenomena, observed in the example of the prevention of sudden death by antiarrhythmic drugs and betablockers, have the effect of impeding research in this complex field and the development of new and potentially useful drugs. It has become necessary to reevaluate the rules of medical experimentation which, in some cases, have reached the limits of feasibility and efficacy.
Clinical Trials as Topic↗
[Value of searching ventricular late potentials in patients recovering from ventricular fibrillation].
The prognostic value of ventricular late potentials (VLP) was studied in 38 survivors of ventricular fibrillation (VF) resuscitated after cardiac arrest. Thirty-seven patients had coronary artery disease, 24 within one month of myocardial infarction, and one patient had valvular heart disease. There were 7 deaths within 2 years, including 5 sudden deaths, the average follow-up in the remaining patients being 46 +/- 30 months. Bad prognostic factors included low left ventricular ejection fraction, anterior myocardial infarction, VF occurring after the first 24 hours of myocardial infarction and the presence of VLP. The 2 year mortality rate was 35% in patients with VLP compared with only 5% when they were absent (p < 0.05). The subgroup with the highest risk of death was that of anterior myocardial infarcts with VLP (45% 2 year mortality). The clinical circumstances surrounding VF were important; patients with clinical and electrical signs of ischaemia at the time of VF tended to have a better prognosis than the others, especially in the absence of VLP: in this subgroup of 12 "ischaemic" VFs without VLP the mortality at 2 years was nil, whereas the other 26 patients had a 27% death rate (0.05 < p < 0.10). Programmed ventricular stimulation was only carried out in 14 cases: it showed that the long-term mortality was very high (60%) in patients with VLP and inducible ventricular tachycardia (VT). Therefore, the implantation of an automatic defibrillator device would seem to be justified in patients resuscitated from VF who have both VLP and inducible VT, but of no value in cases of "ischaemic" VF without VLP.
Action Potentials↗
[Long term course of catecholaminergic polymorphic ventricular tachycardia in children. Apropos of 20 cases with an 8 year-follow-up].
BACKGROUND: Primary ventricular arrhythmias are rarely seen in children. Some of them have a poor prognosis; they should be diagnosed because adequate treatment can prevent sudden death. POPULATION AND METHODS: Twenty children (11 male, nine female), aged 3 to 16 years (mean: 7.7 +/- 4), with apparently normal hearts and normal QTc intervals were referred for stress or emotion-induced syncope. Primary ventricular arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvos eventually degenerating into ventricular fibrillation, was reproducibly induced by physical exertion. The syncopal events and "torsades de pointe" disappeared with beta-blocking therapy. A total of four syncopal events and two sudden deaths occurred during a mean follow-up of 8 years, probably due to discontinuation of treatment. DISCUSSION: Fifty-four-cases of stress-induced severe polymorphous ventricular arrhythmia have been reported in the literature. There were four sudden deaths in 37 patients on beta-blocking therapy, and ten sudden deaths in 21 untreated patients. CONCLUSION: Clinically close to the congenital long QT syndrome, this primary ventricular arrhythmia must be looked for in cases of stress or emotion-induced syncope. The diagnosis relies on Holter monitoring and a stress test. Life-long beta blocker therapy is required.
Adolescent↗
[Indications for implantable automatic defibrillators].
The automatic implantable defibrillator is an effective therapeutic tool for palliative treatment of severe ventricular arrhythmias. There is a significant reduction in sudden death in implanted patients. However, reliable data on the long term global mortality is not yet available. The indications are difficult to define apart from special cases. A large number of factors has to be taken into consideration: the clinical presentation of the arrhythmia, and the different medical and non-medical therapeutic options. At present, it is not possible to arrive at a consensus on the indications of automatic implantable defibrillators. Therefore, it is illusory to construct decisional algorithms. The authors suggest therapeutic orientations rather than strict clinical indications, based on recommendations published by the working groups on cardiac arrhythmias and pacing of the European Society of Cardiology and on their own personal experience.
Death, Sudden, Cardiac↗
Late potentials in arrhythmogenic right ventricular dysplasia. Prevalence, diagnostic and prognostic values.
A time-domain signal-averaged ECG was performed in 52 patients with arrhythmogenic right ventricular dysplasia (ARVD) proven by angiography, in 45 control subjects with normal hearts, and in 132 patients with various types of ventricular arrhythmias and no evidence of cardiac disease during routine cardiac examination. Based on the results of control subjects, patients with at least 2/3 abnormal parameters (QRS > or = 113 ms, LAS > or = 38 ms, RMS 40 < or = 16 microV) were considered as having late potentials (LP). Prevalence of LP was 75% (39/52) in patients with ARVD, 19% (25/132) in patients with apparently idiopathic ventricular arrhythmias, and 4% (4/45) in controls (P < 0.01). In ARVD, no relationship was found between LP and age, type of ventricular arrhythmia (sustained or not), or extent of the disease on angiography. A significant correlation was found between the values of two parameters (QRS and LAS length) and the delay between the first ventricular arrhythmia and the examination (r = 0.39 and 0.42 respectively, P < 0.01). Further examinations (echo and/or angiography) revealed underlying heart disease in 26/132 patients with apparently normal hearts, including 13 with ARVD. LP were present in 21/26 patients (81%) with diseased heart vs 4/106 (4%) in those with normal hearts after complete examination, giving a sensitivity of 86%, and a specificity of 96% for detecting underlying heart disease. During a follow-up of 3.1 +/- 1.2 years after signal-averaged ECG, only one patient died from heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗