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Biomedical subjects

A Leenhardt

Publications and source records attributed to A Leenhardt.

At least 73 records · Page 4Linked to original sources

[Torsades de pointes with short coupling interval].

The authors describe a ventricular arrhythmia observed in 14 patients between 1972 and 1991, and 9 cases in the literature. The patients were hospitalised for investigations of syncope related to torsades de pointes. They were characterised by the very short coupling interval to the initiating extrasystole (average: 245 ms), by the young age of the patients (average: 34.6 years) and by the absence of overt cardiac disease. The resting electrocardiogrammes were normal, especially ventricular repolarisation. Some recordings showed isolated ventricular extrasystoles with short coupling intervals. Quite often, a family history of sudden death was obtained. These episodes of ventricular arrhythmia may degenerate to ventricular fibrillation. Pharmacological and electrophysiological investigations did not show any consistent characteristic electrophysiological behaviour. Investigations of autonomic nervous system function showed a decrease in global sinus rhythm variability and an increased sympathetic over parasympathetic activity. The clinical outcome of these patients is unpredictable with present methods. From a therapeutic point of view, Class I antiarrhythmics, betablockers and amiodarone were ineffective. Verapamil showed an electrocardiographic improvement by increasing the coupling interval of the extrasystoles and decreasing or even suppressing some repetitive forms, but without preventing recurrences. The indications for an implantable automatic defibrillator should be considered in this group of patients. These patients have clinical and electrocardiographic abnormalities which are sufficiently coherent for them to constitute a new pathological entity which the authors suggest calling "torsades de pointes with a short coupling interval".

Defibrillators, Implantable↗

Efficacy of beta-blocking agents in reducing the number of shocks in patients implanted with first-generation automatic defibrillators.

The efficacy of beta-blockers was tested in 11 patients who avoided sudden death as a result of ventricular tachycardia or fibrillation due to coronary artery disease or non-ischaemic underlying heart disease, after implantation of an automatic defibrillator. Ten patients initially tolerated acebutolol despite prior class III or IV heart failure in six cases; nadolol replaced acebutolol in nine cases for long-term therapy. In these 10 patients, periods of treatment with and without beta-blocking agent were available, making possible a crossover comparison, during a follow-up lasting 31.6 +/- 17.8 months. One hundred and ten shocks were delivered: 14 were considered as probably inappropriate and ruled out, leaving the remaining 96 shocks to be analysed. The monthly rate of shocks was lower during beta-blocking treatment: 0.12 +/- 0.24 vs. 1.09 +/- 1.41 (P = 0.03). While taking beta-blockers, only four patients received shocks, compared to 10 (i.e. all cases) not administered beta-blockers (P less than 0.01). Despite the technical limitations of the study, since only a few spontaneous shocks could be documented on ECG recordings, the efficacy of beta-blockers in preventing occurrence of severe ventricular tachyarrhythmias seems likely, and deserves further investigations using new implanted devices with improved memory functions.

Acebutolol↗

[Pro-arrhythmia effect of pyridostigmine. Apropos of a case].

A coronary patient with myasthenia gravis with a previous myocardial infarction presented with severe ventricular arrhythmias after the replacement of neostigmine by pyridostigmine for the treatment of the myasthenia. These arrhythmias were resistant to antiarrhythmic therapy associating betablockers and amiodarone throughout treatment with pyridostigmine but regressed when this drug was withdrawn. A test of reintroduction of pyridostigmine under medical surveillance led to the reappearance of the ventricular hyperexcitability, so confirming the responsibility of this drug. This would seem to be the first reported case of severe ventricular arrhythmias due to a proarrhythmic effect of pyridostigmine. The possible mechanisms of this effect are discussed.

Coronary Disease↗

[Clinical aspects of polymorphic ventricular tachycardia].

Polymorphic ventricular tachycardia is defined as constant change of the QRS morphology. The diagnosis has important etiological, therapeutic and prognostic implications. This term covers several different entities which may be artificially distinguished by the electrocardiographic appearances during tachycardia, by changes of the resting electrocardiogramme, the mode of onset, the presence or absence of underlying cardiac disease and of intercurrent drug therapy. However, as the resting ECG may not be available in an emergency situation, or difficult to interpret, the clinical context is the key to diagnosis and treatment. Polymorphic ventricular tachycardia is classified according to the absence or presence of underlying cardiac disease respectively as torsades de pointe with long QT, torsades de pointe with a short coupling interval and catecholamine-induced ventricular tachycardia of childhood on the one hand, and, iatrogenic torsades de pointe, ventricular tachycardia in acute or chronic infarction and other cardiac diseases, on the other hand. Finally, the authors discuss the problem of polymorphic ventricular tachycardia induced by programmed ventricular stimulation.

Anti-Arrhythmia Agents↗

[Value of signal-averaged electrocardiogram in ventricular arrhythmia without apparent heart disease].

Signal-averaged electrocardiography was performed in 132 subjects with various ventricular arrhythmias without clinically apparent heart disease and compared with the results obtained in a series of 45 normal subjects. The latter enabled definition of the following criteria of normality: QRS duration after averaging < 113 ms; Simson vector of the last 40 ms (RMS40) > or = 17 microV; low amplitude signal duration over 40 microV < 38 ms for a high pass bidirectional filter of 40-300 Hz. Complementary investigations (echo or angiography), performed in all cases, showed underlying abnormalities in 26 patients: 13 right ventricular dysplasias, 7 cardiomyopathies, 3 mitral valve prolapses and 3 minor congenital heart defects. These investigations were normal in the remaining 106 subjects. Of the 26 patients with cardiac disease, 15 had 3 criteria of positivity for late ventricular potentials, 6 had 2 criteria and the other 5 had no criteria of late ventricular potentials. Therefore, 81% of cases with cardiac disease had at least 2 diagnostic criteria of late ventricular potentials whereas only 4% of those without cardiac disease, and in the control group, had criteria of positivity (p < 0.001). Using these criteria, the predictive value of signal-averaged electrocardiography for the detection of underlying cardiac disease was good when 2 criteria are required for diagnosis of late ventricular potentials: sensitivity 81%, specificity 96%; predictive value of a positive test 78%, predictive value of a negative test 97%. Signal-averaged electrocardiography is therefore a good non-invasive method of diagnosing underlying cardiac disease in patients with ventricular arrhythmias without clinically apparent heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term follow-up after sustained monomorphic ventricular tachycardia: Causes, pump failure, and empiric antiarrhythmic therapy that modify survival.

We analyzed the actuarial cardiac mortality rate of 295 consecutive patients with sustained monomorphic ventricular tachycardia who were referred to us between 1978 and 1988. Patients were divided into four groups: group I of 156 patients with coronary disease, group II of 55 patients with nonischemic left ventricular disease, group III of 65 patients with right ventricular disease, and group IV of 19 patients without detectable heart disease. Patients were treated empirically according to a prospective schema: (1) class I antiarrhythmic drugs, (2) in case of recurrence of ventricular tachycardia: amiodarone or beta-blockers, (3) in case of recurrence of ventricular tachycardia: drug combinations or surgery. The mean follow-up duration was 61 +/- 40 months after the first occurrence of ventricular tachycardia, and the clinical outcome was known in 67.5% of patients at 5 years. The actuarial mortality rates were considerably higher in groups I and II compared with those in groups III and IV (p less than 0.01). The mortality rate was slightly higher in group I than in group II (p less than 0.05). In groups I and II, actuarial mortality rate were much higher when left ventricular ejection fraction was less than 0.30 (p less than 0.01). Comparisons between treatments showed no difference in actuarial mortality rates in patients with ventricular tachycardia and left ventricular ejection fraction greater than 0.30.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Influence of amiodarone on genetically determined drug metabolism in humans.

Amiodarone has been shown to interact with the nongenetically determined hepatic elimination of several drugs, including phenytoin and digoxin. Its influence on genetically determined metabolic pathways has not been studied in humans. We examined the effects of oral amiodarone therapy on the genetically determined metabolism of isoniazid (N-acetyltransferase), mephenytoin (cytochrome P450MEPH), and dextromethorphan (CYP2D6). Eight patients with arrhythmias were studied before and 76 +/- 16 days after amiodarone (loading dose of 1000 mg/day for 10 days followed by a maintenance dose of 200 to 400 mg/day). Genetically determined enzyme activity was assessed indirectly by calculating the metabolic ratio (parent drug/metabolite in 8-hour urine for CYP2D6 and P450MEPH and N-acetylisoniazid/isoniazid in plasma for N-acetyltransferase) after oral administration of the parent compounds. At the time of phenotyping, plasma concentrations of amiodarone and N-desethylamiodarone were 0.66 +/- 0.35 micrograms/ml and 0.65 +/- 0.26 micrograms/ml, respectively. Amiodarone increased the log(metabolic ratio) of dextromethorphan from a median of -2.5 (range, -2.9 to -2.0) to a median of -1.9 (range, -2.5 to -1.5; p less than 0.02) but did not alter the metabolic ratio of mephenytoin or isoniazid. The amount of dextromethorphan excreted in urine increased from a median of 0.084 mumol/8 hours (range, 0.041 to 0.161 mumol/8 hours) to a median of 0.205 mumol/8 hours (range, 0.064 to 0.288 mumol/8 hours; p less than 0.02) and the amount of its metabolite (dextrorphan) tended to decrease from a median of 26 mumol/8 hours (range, 15 to 37 mumol/8 hours) to a median of 20 mumol/8 hours (range, 7 to 27 mumol/8 hours; p less than 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heart rate variability in left ventricular hypertrophy and heart failure, and the effects of beta-blockade. A non-spectral analysis of heart rate variability in the frequency domain and in the time domain.

An analysis of heart rate (HR) variability (HRV) was based on quantifying the number and amplitude of HR fluctuations over long (8-30 cycles) and short (2-4 cycles) sequences of acceleration and deceleration-forming oscillations. The 'product' (number times amplitude) is an equivalent of the power spectrum in the frequency domain. In the time domain, positive correlations with HR were found for the number of long (L) sympathetic-mediated oscillations, whereas they were negative for short (S) vagally-mediated oscillations. The L/S ratio, an index of the autonomic nervous system (ANS) balance, closely paralleled the circadian HR values. HRV was studied in the ambulatory ECG of three groups of 15 normal adults (group I), 13 patients with left ventricular hypertrophy (LVH, group II) and 13 patients with heart failure (HF, group III). In basic conditions the mean HR was 77.1 +/- 1.9 beats min-1 (mean +/- SEM) in group I, 76.8 +/- 3.3 in II, 79.5 +/- 3.5 in III (P = NS). The different types of oscillations had smaller 24-h average values of the product in groups II and III than in group I, but the trends did not reach significance. However, the pooled 24 hourly values of the L/S ratio in group I (1.17 +/- 0.09) were lower than in group II (1.33 +/- 0.06, P less than 0.05 at Ancova) and higher than in group III (1.06 +/- 0.09, P less than 0.001). A 3-day treatment with acebutolol non-uniformly slowed the mean HR:--9.5% in group I, --18.1% in II and -19.1% in III (P less than 0.001), and uniformly diminished the L/S ratio by 17% to 20% (P less than 0.01). In conclusion, the sympathetic predominance of the ANS balance in LVH and HF is reflected by the beta-blockade induced HR decrease that is twice as marked in patients as in controls. In basic conditions HRV tends to be depressed in LVH and even more in HF. The ANS imbalance, however, has different modalities depending on the presence of HF, probably because of the different status of beta-adrenergic receptors in this condition.

Acebutolol↗

Sudden cardiac death, implanted defibrillation, and clinical electrophysiology.

A mere 25 years ago, the technique of external defibrillation became the starting point for the development of clinical electrophysiology by permitting routine use of endocavitary programmed electrical stimulation of the heart without undue risk. Major advances in knowledge of clinical arrhythmias and the understanding of their mechanisms were, thus, permitted. Mirowski's implanted defibrillator also constituted a major breakthrough therapeutically; unfortunately, however, some 10 years later, it has not yet induced similarly hoped for consequences in terms of progressing knowledge concerning lethal arrhythmias, largely due to the absence of Holter functions in the implanted devices. As a result of this, in our opinion, better established therapeutic indications are still needed. The reasons for the present situation, we believe, may be partly technical but are conceptual as well. The key point is that even the clear demonstration of the great practical efficacy of a therapeutic tool does not exempt us from the obligation of determining the mechanisms of this effect.

Arrhythmias, Cardiac↗

[Implantable automatic defibrillator. Evaluation after 8 years of use].

The thirty nine patients (30 men and 9 women, mean age 49 +/- 14 years) who were implanted with an automatic cardioverter defibrillator (AICD) between October 1982 and April 1990 were reviewed retrospectively. This group included 22 patients with ischaemic cardiomyopathy (55%), 9 primary cardiomyopathies (23%) 5 ventricular tachycardias in patients with normal hearts (13%), 1 case of arrhythmogenic right ventricular dysplasia and two of mitral valve prolapse. The mean ejection fraction for the whole group was 38 +/- 14%. The indication for implantation of the AICD was life-threatening ventricular arrhythmias for which other forms of treatment were either ineffective (29 patients), impossible to assess (9 patients) or poorly tolerated (1 patient). Two patients died during the perioperative period and the follow-up is too short in two other cases. Therefore, 35 patients were studied over an average of 23.7 +/- 16 months. During follow-up, 5 patients died, 3 of progressive cardiac failure and 2 suddenly, one of whom was waiting for a replacement of an exhausted generator. The AICD never functioned in 40% of patients. In addition, it was impossible to determine for the majority of shocks delivered if they had been triggered by a sustained ventricular arrhythmia. Long term tolerance was generally good but two patients developed cardiac constriction induced by the epicardial patch electrodes. The results of this review confirm the efficacy of AICD in preventing sudden death at the expense of a low operative mortality and with good long term tolerance. Quite a large proportion of AICDs never functioned and the interpretation of the delivered shocks remains questionable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Life expectancy after a first attack of sustained monomorphic ventricular tachycardia. Apropos of 295 patients with a follow-up of more than 5 years].

Analysis of actuarial cardiac mortality of 295 patients after a first attack of sustained monomorphic ventricular tachycardia followed up for an average of 5.1 years showed that: the aetiology was the main prognostic factor. Patients with a normal left ventricle had a zero 5 year mortality rate (normal heart) or 3% (arrhythmogenic right ventricular dysplasia) compared with 24% in patients with cardiomyopathy and 40% with myocardial infarction: p less than 0.01. Similar results were obtained if sudden death was considered; in patients with left-ventricular disease, the role of pump function assessed by the ejection fraction was essential: the 5 year mortality was 14.5% (cardiomyopathy) and 30% (myocardial infarction) if this was greater than 0.3 compared to 43% and 51% respectively when less than 0.3 (p less than 0.01); the heart rate of spontaneous ventricular tachycardia and that of tachycardia induced during endocavitary investigation had no influence on the mortality. However, the mortality following a first tachycardia with syncope was higher than that following a well tolerated tachycardia (p less than 0.5 if the ejection fraction less than or equal to 0.3 and p less than 0.001 if greater than 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Mental activity, adrenergic modulation, and cardiac arrhythmias in patients with heart disease.

All of the electrophysiological mechanisms of arrhythmias are sensitive to the influences of the autonomic nervous system, particularly to its adrenergic limb. Arrhythmogenic areas may also be dependent on the inhomogeneity of these influences because of their pathophysiological structure and/or the neurogenic or humoral nature of the vector of modulation. The complexity of the various possible scenarios, combined with the role of the rate dependence, explains why standardized protocols exploring the autonomic nervous system in clinical arrhythmias are difficult to define. Invasive electrophysiology is not adapted to address the problem. Isoprenaline infusion only reproduces the humoral adrenergic stimulation to which only a few types of arrhythmias are sensitive. The exercise test is a very complex investigation if the multiple parameters involved are considered. Only a part of its limitations are obviated by the mental stress. Under natural conditions, the neurogenic origin, the intensity of the sympathetic stimulation, and its suddenness are all critical factors responsible for severe tachyarrhythmias. Arrhythmias of the long QT syndrome are particularly demonstrative of the importance of the autonomic nervous system, but this evidence can also be documented in more trivial circumstances of diseased or apparently undiseased hearts. Exploring the autonomic nervous system behavior through heart rate variability in ambulatory recordings is the most recent and fruitful method of investigation. This nonprovocative approach has technical obstacles and practical and theoretical limitations related to the fundamental nature of the autonomic nervous system, which is both a marker of the cardiac status and a determinant of arrhythmias.

Arrhythmias, Cardiac↗

Predictive value of electrophysiologic studies during treatment of ventricular tachycardia with the beta-blocking agent nadolol. The Working Group on Arrhythmias of the French Society of Cardiology.

Sixty patients with recurrent inducible sustained ventricular tachycardia were prospectively treated with nadolol (40 or 80 mg/day). Old myocardial infarction was present in 43 patients and dilated cardiomyopathy in 12. In group I (n = 36), nadolol was given alone, whereas in group II (n = 24), previously ineffective treatment with amiodarone was continued in combination with nadolol. Left ventricular ejection fraction was higher in patients in group I (0.40 +/- 0.12) than in group II (0.30 +/- 0.10, p less than 0.01) patients. Electrophysiologic study was repeated after short-term treatment with nadolol, which was continued regardless of the results of this test, according to the scheme of the parallel approach. Recurrence of spontaneous tachycardia or sudden death occurred in 21 patients after 10 +/- 9.2 months; sustained tachycardia was inducible in 19 on nadolol therapy. The remaining 39 patients (of whom 21 had inducible tachycardia while taking the drug) have had no recurrence of tachycardia after 27.8 +/- 9.3 months of follow-up study. Sensitivity, specificity and predictive value of a positive and negative test were 90.5%, 46%, 47.5% and 90%, respectively. The results differ between group I and group II patients, the latter having a high percent of false positive responses. This difference is even more obvious with respect to left ventricular ejection fraction: the predictive value of a positive test was 86% when ejection fraction was greater than 0.40 and 39% when it was less than 0.40.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Signal-averaged electrocardiography in right ventricular dysplasia].

The authors report their experience of signal-averaged electrocardiography (SAE) in arrhythmogenic right ventricular dysplasia (ARVD) in a study comparing the results in 40 control subjects, 21 patients with ARVD with episodes of sustained monomorphic ventricular tachycardia (VT) (Group I), 7 patients with ARVD without sustained VT (Group II) and 10 asymptomatic members of the families of patients in Group I (Group III). There were significant differences in the results of SAE in the time domain between the control group and Group I, patients with "classical" ARVD. The RMS 40 (root mean square of the last 40 ms of the QRS complex) was the most sensitive parameter but the specificity was less than the averaged QRS width and the low amplitude signal duration. The results in Group II were more varied, some patients having clearly abnormal SAE and others strictly normal recordings. In Group III, the investigation was normal. Spectral analysis after Fourier transformation did not show significant differences between the 3 groups. A difference was observed between the diffuse and localised forms of ARVD in Groups I and II: the localised forms had a shorter QRS width and low amplitude signal duration than the diffuse forms. Also, there was a relationship in Group I between age and duration of QRS and delayed potential which increased and with the RMS 40 or 50 which decreased. This is an argument in favour of the progressive nature of ARVD with respect to time.

Adult↗

[Late potentials and arrhythmogenic right ventricular dysplasia].

The authors report on their experience in investigating late potentials (LPs) in arrhythmogenic right ventricular dysplasia (ARVD), by comparing 35 patients with ARVD with 40 control subjects. The values of QRS and RMS40 and the duration of the LP showed a marked difference between the control group and the ARVDs, particularly if sustained VT was present. In this case, 68 per cent of patients were found to have LPs (with at least 2 out of 3 parameters abnormal) versus 50 per cent in the ARVDs without sustained VT and 5 per cent in the controls. There was a difference between the diffuse forms (10 per cent) and the localized forms (25 per cent) of ARVD: the LPs were markedly more obvious in the diffuse forms. Likewise, there was a clear relationship between age and the criteria for LPs in ARVD with sustained VT. This is an argument in favour of the evolutive character of the disease, which could be observed directly in a few cases in which the examinations were repeated over the course of time.

Adult↗

Surgery for the Wolff-Parkinson-White syndrome in 73 consecutive patients: what have we learnt from intraoperative mapping?

Intraoperative epicardial mapping data obtained in 73 consecutive patients operated upon for the Wolff-Parkinson-White syndrome were reviewed. Fifty-six patients had single and 17 patients had multiple accessory pathways. Except for right free wall pathways, all bypass tracts were divided using an endocardial approach. There were 2 operative deaths, 1 of which occurred after a concomitant mitral valve replacement. A total of 78 of the 87 pathways present in the 71 survivors were successfully ablated (90%). All failures occurred in patients with left posterior septal pathways. Epicardial mapping performed prior to bypass was found helpful in identifying multiple distinct accessory pathways which had been missed preoperatively. This occurred in 6 patients and led to appropriate combinations of classic operative approaches which resulted in all of these pathways being successfully divided. Further, by demonstrating that Kent bundles often presented as multiple closely-spaced or arborized accessory pathways, intraoperative mapping led to widening of the margins of surgical dissection, and in particular to an additional left atriotomy in all cases of left posterior septal accessory pathways which resulted in a substantial improvement in our rate of success.

Adolescent↗

Results of electrical fulguration in arrhythmogenic right ventricular disease.

Eleven patients with sustained ventricular tachycardia (VT) refractory to antiarrhythmic drugs due to right ventricular disease shown by angiography underwent fulguration. Seven patients always had VT with the same morphology, and 4 had clinical VT with 2 or 3 different QRS waveforms. Five patients underwent a single fulguration and the other 6 underwent from 2 to 5 procedures; 2 to 14 shocks (mean 6) of 150 to 250 J were used. No serious complications occurred. At 31.5 +/- 9 months of follow-up, the arrhythmia was controlled in 8 patients, with continuation of previously ineffective antiarrhythmic drug therapy in 6 of 8. The number of VT episodes the year before and after fulguration was 0.5 +/- 0.7 vs 3.5 +/- 1.7 (p less than 0.001). There was no statistically significant difference between the success rate and the degree of prematurity of the onset of the local electrogram during VT: -36 +/- 31 ms for successes and -38 +/- 13 ms for failures. In 7 patients with monomorphic VT, there were 6 successes and 1 failure, and in 4 patients with several morphologies of VT, there were 2 successes and 2 failures (1 due to the appearance of a "new" VT). Thus, electrical fulguration of VT in patients with right ventricular disease is safe and most often effective, particularly in patients with monomorphic VT, when combined with antiarrhythmic drugs. In these patients, the usually recommended endocardial mapping criteria for the determination of the optimal fulguration site were not predictive of outcome. Further studies are necessary to better define the optimal site for fulguration.

Adult↗

[The implantable defibrillator. Long-term clinical results].

Between october, 1982 and december, 1986, 17 patients were implanted with an automatic defibrillator. The thoracic route was used in 6 patients with installation of an epicardial patch and an endocavitary electrode. The subcostal route was used in the remaining 11 patients, with 2 epicardial patches. The device, badly tolerated by 2 of the first 6 patients, created no problem in the 11 patients of the second group. One patient died of pulmonary embolism on the 6th post-operative day. At follow-up, there was no inappropriate triggering of the AID-B: 8 patients had neither arrhythmia nor shock, and 8 received from 2 to 55 shocks with documented arrhythmia. Two patients died suddenly: one after end of life of the device, the other after 3 years, while the device was still working. The implantable defibrillator technique has improved and local complications are now seldom observed. The device is reliable and constitutes an effective weapon against sudden death caused by ventricular arrhythmia.

Adolescent↗