Immunochemical evidence for the species-specificity of mammalian cardiac myosin and heavy meromyosin.

Structural differences between various myosins were investigated by means of antibodies to heavy meromyosin, a tryptic subfragment of myosin. Heavy meromyosin was purified from rabbit white skeletal and from pig and human cardiac muscles by gel filtration, and antisera were produced in guinea pigs. Analyses, carried out with the quantitative micro-complement fixation technique, indicated that the antibodies were specific to heavy meromyosin and myosin and not to other contractile proteins. For each muscle type, the corresponding intact myosin reacted, and the degree of dixation was always lower than with heavy meromyosin (50 and 70% fixation respectively). This vertical shift was the same for the three muscle types, indicating that the heavy meromyosin represent corresponding fragments of the myosin molecule from one muscle to the other. Antisera to pig or human cardiac heavy meromyosin clearly distinguished antigens (heavy meromyosins, myosins, or crude extracts) from the ventricles of various heterologous species. Relative to pig, the immunological distances were 50 for the rabbit, 73 for the rat and greater than 100 for human and mice. Relative to human, these values were 20 for the rat, 60 for the rabbit, 72 for the pig. These data provide direct evidence that mammalian cardiac myosin is species-specific.

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)

[Long-term evaluation of endocavitary cryoablation of nodal reentry]. / Evaluation à long terme de la cryoablation endocavitaire dans le traitement des réentrées nodales.

Radiofrequency ablation is the reference treatment of refractory nodal reentry. Cryoablation has the advantage of having more modulable effects and minimises the risk of permanent atrioventricular block (AVB). Its immediate efficacy seems comparable to that of radiofrequency ablation but the long-term results are not well known. Endocavitary cryoablation of the slow pathway was undertaken in 26 patients (18 women) with an average age of 47.7 +/- 72.8 years with re-entrant nodal tachycardia refractory to medical therapy. The primary success rate was 92% (24 out of 26). On average, 2.6 +/- 2.2 (1 to 10) cryoablations at - 70 degrees C were delivered and were preceded by 6.4 +/- 4.5 (1 to 16) cryomappings to locate the site of the slow pathway. During cryomapping, 8 episodes of AVB were observed in 6 patients (6 second or third degree), all of which were revertible on rewarming. No cases of permanent AVB were observed. An oesophageal stimulation test of inducibility was performed on the 4th day in 21 patients, 16 of which were not reinducible. During follow-up of 355 +/- 194 days, 22 of the 26 patients (85%) had no recurrence of the arrhythmia. Two of the 24 primary successes had a recurrence, in addition to the two primary failures. Two of the four recurrences occurred in a non-sustained form which was less disabilitating for the patient and the recurrences were controlled in the 4 patients by antiarrhythmic therapy. These results suggest that cryoablation may be a reliable and effective long-term treatment of re-entrant nodal tachycardias. If confirmed in larger series in terms of efficacy and safety, cryoablation could become the treatment of choice of re-entrant nodal tachycardia.

[New energy sources for ablative methods]. / Nouvelles sources d'énergie dans les méthodes ablatives.

Radiofrequency current is the reference energy source for endocavitary ablation of arrhythmias. It is particularly well adapted for the ablation of focal arrhythmogenic substrates such as accessory pathways or foyers of automatism. Technological advances have made the lesions larger but the extension of the indications of percutaneous ablation to more complex substrates such as atrial fibrillation have justified the evaluation of alternative energies. The production of linear transmural lesions or deeper lesions which respect the parietal myocardial architecture and endocardial structure are a challenge for these energies. The capacity of functional mapping specific to cryogenics has provided this energy source with a clinical application for ablation of high risk structures whereas other energies, despite the chronicity of their experimental evaluation, are still at the stage of preliminary clinical trials with the sophisticated catheters in special indications.

Effect of diltiazem on myocardial infarct size estimated by enzyme release, serial thallium-201 single-photon emission computed tomography and radionuclide angiography.

Diltiazem is a calcium antagonist with demonstrated experimental cardioprotective effects. Its effects on myocardial infarct size were studied in 34 patients admitted within 6 hours after the first symptoms of acute myocardial infarction. These patients were randomized, double-blind to placebo or diltiazem (10-mg intravenous bolus followed by 15 mg/hr intravenous infusion during 72 hours, followed by 4 X 60 mg during 21 days). Myocardial infarct size was assessed by plasma creatine kinase and creatine kinase-MB indexes, perfusion defect scores using single-photon emission computed tomography with thallium-201 and left ventricular ejection fraction measured by radionuclide angiography. Tomographic and angiographic scanning was performed serially before randomization, after 48 hours and 21 days later. Groups were comparable in terms of age, sex, inclusion time and baseline infarct location and size. Results showed no difference in creatine kinase and creatine kinase-MB data between controls and treated patients, a significant decrease in the perfusion defect scores in the diltiazem group (+0.1 +/- 3.0 placebo vs -2.2 +/- 1.9 diltiazem, p less than 0.02) and a better ejection fraction recovery in the diltiazem group (-4.2 +/- 7.4 placebo vs +7.7 +/- 11.2 diltiazem, p less than 0.05). Myocardial infarct size estimates from perfusion defect scores and enzyme data were closely correlated. These preliminary results suggest that diltiazem may reduce ischemic injury in acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Classification and pitfalls of atrioventricular blocks]. / Classification et pièges des blocs auriculoventriculaires.

Atrioventricular blocks may be classified according to their degree, their site and their aetiology. Assessing the degree of block is not always easy when the P waves are poorly visible and/or masked by the ventricular complexes. Affirmation that a 2nd degree block is a Mobitz II block requires examination of the ECG to differentiate it from "false" Mobitz II due to variable PP intervals or concealed hisian extrasystoles. Complete atrioventricular block is easy to define on the ECG but not always synonymous with totally blocked conduction and should be interpreted taking into account the frequency of escape beats. Determining the site of block is important as it has therapeutic implications; the type of block evaluated from the surface ECG also provides useful but not always decisive information. The investigation of the aetiology of the block is valuable for differentiating acute, transient blocks from chronic (permanent or paroxysmal) blocks, the former sometimes requiring temporary but rarely permanent cardiac pacing.

[Electrocardiographic aspects of atrial fibrillations]. / Aspects électrocardiographiques des fibrillations auriculaires.

The electrocardiographic analysis of atrial fibrillation is usually easy. However, some cases may be difficult to interpret: the organisation and voltage of the fibrillation waves can be very variable leading to appearances of atypical flutter in cases with large "f" waves or, conversely, in cases with low voltage fibrillation, to those of sinus mode dysfunction. The ventricular response may be slow: the conduction is usually delayed in the atrioventricular node where concealed conduction plays an important role in determining the ventricular response. Regular ventriculogrammes correspond to a junctional or ventricular escape rhythms. Aberrant conduction in the His-Purkinje system may sometimes be observed after long diastoles (phase 4 block) but often terminates short, preceded by long cycles (phase 3 block). It is usually easy to differentiate them from ventricular ectopics or preexcitation by careful examination and application of classical diagnostic criteria.

[Drug treatment of chronic ventricular arrhythmia]. / Traitement médicamenteux des arythmies ventriculaires chroniques.

The treatment of chronic ventricular arrhythmias depends on the severity and tolerance of the arrhythmia. Extrasystoles, even repetitive, in the healthy heart, are usually respected when asymptomatic or treated with betablockers in first intention when symptomatic. These drugs should also be proposed for patients with ischemic heart disease and non-sustained ventricular tachycardia, a situation in which Class I antiarrhythmics should be avoided. The prevention of sustained ventricular tachycardial may be empirical, with betablockers and/or amiodarone, or guided by the results of pharmacological tests during endocavitary electrophysiological studies.

[Radiofrequency ablation of accessory atrioventricular pathways]. / Ablation des voies accessoires par radiofréquence.

Since its introduction at the beginning of the 1980s, radiofrequency ablation of accessory atrioventricular pathways has become method because of its excellent results and the indications have increased to cases in which only symptomatic improvement is the objective. These advances have been made possible by technical innovations to the generators of the radiofrequency current and, above all, to the ablation catheters which enable mapping nearly all the perimeter of the atrioventricular rings and reach all the accessory pathways irrespective of their site. The approach depends on the localisation of the accessory pathway but the criteria of mapping are the same: detection of a specific accessory pathway potential, precession or concordance (depending on the topography) of the initial peak of the endocavitary ventriculogramme and the onset of the delta wave on the surface ECG, QS morphology of the ventriculogramme on monopolar recording, shortest VA' interval in orthodromic reciprocating tachycardia for latent kent bundles. In specialised centres, the global success rate is 90 to 98% but certain sites, especially the right lateral pathways, are more difficult to attain. The complication rate is about 4% but it tends to decrease with the experience of the operating teams and close monitoring of the patients. However, there persists an uncertainty concerning potentially arrhythmogenic effects of the lesions induced which justifies restricting the indications in young children.

[Bitachycardia]. / Les bitachycardies.

One or several episodes of bitachycardia (a simultaneous ventricular tachycardia and atrial tachycardia or fibrillation) were observed in 13 patients. An oesophageal or right atrial endocavitary recording is usually necessary to show the atrioventricular dissociation: even then the diagnosis may be difficult in cases of isorhythmic dissociation or when the ventricular tachycardia is irregular. In 5 cases the double tachycardia appeared to be coincidental. In 7 patients the ventricular tachycardia seemed to be dependant on the atrial tachycardia and could be initiated by a simple spontaneous atrial extrasystole in 3 cases. In one patient the ventricular tachycardia, after a phase of retrograde conduction to the atria, initiated the atrial arrhythmia. The therapeutic indications depend in part on the eventual relationship between the two arrhythmias.

[How to evaluate the arrhythmogenic risk after myocardial infarction?]. / Comment évaluer le risque arythmique au décours d'un infarctus du myocarde.

The risk of sudden arrhythmic death after myocardial infarction is high, especially during the first months. The evaluation of this risk should be performed before hospital discharge in the same way as residual ischaemia and left ventricular function, which are independent risk factors for arrhythmia, are assessed. Holter monitoring provides information not only about ventricular hyperexcitability (especially the detection of unsustained ventricular tachycardia) but also about the activity of the autonomic nervous system by analysis of variations of the sinus rhythm, the decrease of which carries a poor prognosis. The search for an arrhythmogenic substrate requires signal averaged electrocardiography, but although the absence of late potentials carries a good prognosis, the positive predictive value of this investigation is very low. The association of non-invasive indices of poor prognosis greatly increases the probability of a major arrhythmic event; this may require consideration of programmed ventricular pacing, another method of substrate and risk assessment, which has the added advantage of sometimes indicating the most appropriate therapy.

[Electrophysiological mechanisms of ventricular arrhythmia in myocardial infarction]. / Mécanismes électrophysiologiques des arythmies ventriculaires de l'infarctus du myocarde.

In experimental models of coronary occlusion, the physiopathology of ventricular arrhythmias varies with its timing, there being three main phases: early, late and chronic. The early phase covers the first 30 minutes and is dominated by tachycardias and fibrillations resulting from multiple micro-reentry circuits which are the consequence of major changes in conduction and excitability created by acute ischaemia. These arrhythmias may be triggered by extrasystoles which have a different mechanism related to the injury current generated in the border zone between ischaemic and healthy cells. The late phase lasts about 72 hours: it is characterised by polymorphic ventricular extrasystoles and bursts of relatively slow ventricular tachycardia. Much more rapid tachycardia can be induced by stimulation. The origin of these arrhythmias is usually in the surviving Purkinje fibres of the subendocardium. The mechanisms are variable: abnormal automaticity, reentry or activity triggered by delayed after depolarisations. During the chronic phase, reentrant tachycardia is possible but only when induced by stimulation. Delayed conduction is the consequence of non-uniform antisotropism related to the disorientation of the myocardial fibres caused by fibrosis. In the clinical situation, most research has been centered on sustained monomorphic ventricular tachycardias of the chronic phase. Their mechanism is almost exclusively reentry (the circuits usually being located in the subendocardium) as suggested by the triggering and interruption of clinical tachycardias by stimulation, the recording of fragmented activation or prepotentials at the site of emergence of the tachycardia and the phenomena of pacing.

[Double responses]. / Les doubles réponses.

Double response is a rare electrocardiographic phenomenon requiring two atrioventricular conduction pathways with very different electrophysiological properties. Double ventricular responses are the usual manifestation: an atrial depolarisation (spontaneous or provoked, anticipated or not) is followed by a first ventricular response dependent on an accessory pathway or a rapid nodal pathway and then a second response resulting from sufficiently delayed transmission through a nodal pathway for the ventricles to have recovered their excitability when the second wave of activation reaches them. A simple curiosity when isolated and occurring under unusual conditions, particularly during electrophysiological investigation of the Wolff-Parkinson-White syndrome, the double response may initiate symptomatic non-reentrant junctional tachycardia when associated with nodal duality and repeating from atria in sinus rhythm. The functional incapacity and resistance to antiarrhythmic therapy may require referral for ablation of the slow pathway.

[Fragmenting of the His potential after atrial stimulation]. / Fragmentation du potentiel hisien après extrastimulus auriculaire.

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

[Double Wenckebach phenomenon at nodal and His levels. Electrophysiological demonstration in slow and irregular flutter]. / Double phénomène de Wenckebach, nodal et hisien. Démonstration électrophysiologique dans un flutter lent et irrégulier.

The authors describe the analysis of a case of atrial flutter with a slow ventricular response, the block being 9:2 with a first RR interval measuring between 3 and 4 PP intervals and a second RR interval between 5 and 6 PP intervals, the second of the 2 RR intervals being exactly 9 PP intervals. The only possible explanation of this sequence is firstly a 3:1 intranodal block (Wenckebach 3:2 in the central zone N of the node and 2:1 block at the nodo-hisian junction) followed by a 3:2 infra- or intra-hisian Wenckebach phenomenon. The His bundle recordings during flutter confirmed this hypothesis with the recording of a 3:2 block after the H potential. When sinus rhythm was restored at atrial level, the intrahisian conduction defect persisted (2:1 or 3:2 Wenckebach block).

[Late recurrence of atrioventricular block in acute anterior and/or septal myocardial infarcts. Discussion of the implantation of a permanent pacemaker. Apropos of 2 cases]. / Récidive tardive du bloc auriculo-ventriculaire des infarctus du myocarde aigus antérieurs et/ou septaux. Discussion de l'implantation d'un pacemaker définitif. A propos de deux observations.

Does the high incidence of post hospital sudden death in patients surviving acute anterior and or septal infarction complicated by transient intraventricular or atrioventricular block have any relation to a late recurrence of the conduction defect and is prophylactic permanent pacing justified from the outset? These questions remain controversial and, to illustrate the problem, two cases of infarction, one an extensive anterior infarct and the other a deep septal infarct are reported. Both developed late recurrences of atrioventricular block without recurrent myocardial infarction requiring permanent pacing. In practice, the usual poor prognosis of these infarcts make comparative survival studies very difficult. The authors suggest permanent pacing for a very restricted group of patients surviving acute anterior and or septal infarction complicated by transient complete atrioventricular block.

[Acute myocarditis simulating myocardial infarct with regressive heart failure]. / Myocardites aiguës simulant un infarctus myocardique avec insuffisance cardiaque régressive.

Two patients were hospitalised with severe heart failure and hypotension thought initially to be due to acute anterior myocardial infarction because of very suggestive electrocardiographic appearances. Heart failure rapidly regressed in both cases. The young age of these two patients, the pyrexia, rapid and total regression of the ECG appearances, the absence of atheromatous lesions at coronary angiography and clinical cure with a follow-up of 10 years in one of the cases, were factors in favour of the diagnosis of acute myocarditis.

[Radiofrequency catheter ablation: theoretical and technical aspects]. / Ablation par courants de radiofréquence; aspects théoriques et techniques.

Radiofrequency currents produce circumscribed tissue necrosis by progressive and localised heating. Endocardial application via the percutaneous approach with a specific electrophysiological catheter enables destruction of the anatomical substrate of many cardiac arrhythmias. The technique is well tolerated due to the absence of barometric phenomena and general anaesthesia, and the possibility of modulating the energy delivered, which explains why it has supplanted fulguration in most indications. The technological evolution aims to increase the lesional power and decrease the number of complications. This implies the development of catheters capable of delivering greater currents without the risk of thrombus formation and of generators dependent on electrical or thermal parameters. The low incidence of complications reported by centres using the technique is based on an excellent understanding of the technique, the use of appropriate material, the surveillance of parameters which allow detection of unwanted effects and the respect of a strict operation protocol. In the absence of these precautions, the wide diffusion of this technique, favored by its low cost and relative simplicity, may be associated with an increase in the number of side effects which could be lethal. This cannot be accepted in a technique with such wide indications, including arrhythmias with a usually benign long-term prognosis.

[Comparative study of effects of diltiazem, nifedipine and their combination on exercise stable angina]. / Etude comparative des effets du diltiazem, de la nifédipine et de leur association dans l'angor stable d'effort.

Diltiazem and Nifedipine could be synergic. The aim of this study was to investigate the benefits of their association. Eighteen patients, 15 men and 3 women, average age 61 +/- 6 years, with stable angina on effort, were studied. Eight patients had single vessel disease and 10 patients had multivessel disease. The patients underwent a randomised double-blind trial with 4 successive treatment periods each lasting one week: placebo; 360 mg/day of Diltiazem; 60 mg/day of Nifedipine; 180 mg/day of Diltiazem with 30 mg/day of Nifedipine. The benefits were evaluated clinically, by exercise stress testing and with drug plasma concentrations at the end of each sequence. The results at the end of the 3 treatment periods were significantly better than with placebo. Diltiazem was significantly better than Nifedipine with respect to the development of angina during exercise testing (1 patient compared with 7 patients) and to maximum load (118.3 +/- 33.3 watts compared with 105.9 +/- 35.4 watts) (p less than 0.05). The association of the two drugs did not give better results than Diltiazem alone. Compared with placebo, the total duration of exercise testing and the duration of 1 mm ST depression were significantly longer during the 3 treatment sequences but there were no significant differences between each of them. Secondary effects were significantly more common with Nifedipine (7 patients) and with the drug association (9 patients) than with Diltiazem alone (3 patients) or placebo (1 patient). Plasma concentrations of Diltiazem were 328 +/- 35 ng/l with the 360 mg/day dosage and 137 +/- 52 ng/l with the 180 mg/day dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

[Radiofrequency ablation: physical bases and principles]. / Ablation par courants de radiofréquence; bases physiques et principes.

Radiofrequency currents are the reference physical agent for endocavitary ablation, especially of supraventricular tachycardias. They are delivered in a continuous mode or sinusoidal waves. Because of the high frequency between 200 and 3,000 kHz there is no stimulation of the neuromuscular cells. The mechanism of the resulting lesion is essentially related to heating of the biological surroundings of the active electrode. The temperature increase remains localised around the active electrode and its kinetics are progressive, which implies close and stable contact between the active electrode and the tissues. The lesional effect is obtained 60 to 90 degrees C in order to avoid the deleterious effects induced by temperatures of over 100 degrees C: boiling, coagulation, vaporization and carbonization of the tissues leading to an increase in impedence. The volume of lesions depends on many factors which are sometimes difficult to control in vivo. It is more closely correlated to the temperature of the active electrode than to the parameters of delivery (power, duration ...). The histological lesions correspond to scar tissue which respects the surrounding architecture. The major technological innovations of this method have resulted in an increase in the volume of the lesions produced, a reduction in the frequency of undesirable effects such as the formation of coagulum and in an immediate evaluation of the anatomic lesional effect. They have consisted in the introduction of specific electrodes and of systems of monitoring the electrical and thermal effects with the use of imaging techniques such as endovascular and transoesophageal echocardiography and angioscopy. New indications will require development of specific catheter-generator equipment to create lesions of size and shape adapted to the arrhythmogenic substrate.