Clinical pharmacokinetics of levorotatory and racemic disopyramide, at steady state, following oral administration in patients with ventricular arrhythmias.

Electrophysiological effects, antiarrhythmic activity and kinetics of levorotatory disopyramide (R(-) DP) and racemic disopyramide (equimolar mixture of R(-) DP and S(+) DP) were compared in patients with ventricular arrhythmias. This double blind cross-over randomized trial was achieved, at steady-state, following oral administration of 200 mg three times a day. In comparison with baseline values, electrophysiological data indicated that R(-) DP and racemic DP prolonged, significantly and similarly, PR interval (+11.7% and +10%, respectively, P less than .01), and QTc interval (+9.2% and +7%, respectively, P less than .001), while QRS interval was not significantly affected. The antiarrhythmic activity, assessed by percent reduction in ventricular extrasystoles frequency, showed a similar efficiency of levorotatory and racemic DP: 80% and 74%, respectively (P = .24). Ventricular tachycardias disappeared with both treatments in the three patients concerned. During the racemic period, the mean total plasma clearance, expressed as CL/F, of S(+) DP (114.6 ml/min), was significantly lower than that of R(-) DP (157 ml/min), (P less than .001). The mean total plasma clearance of R(-) DP, during the levorotatory period (163 ml/min), did not differ from the respective value determined during the racemic period (P = .32). During the racemic period, the stereoselective difference in total plasma clearances, which is not observed when DP enantiomers are administered separately, may result from an increase in unbound fraction of R(-) DP, due to the presence of S(+) DP, which is known to be a potent displacer of R(-) DP.

Haemodynamic benefit of a rate-adapted A-V delay in dual chamber pacing.

In dual chamber pacing, an improvement of exercise capacity is expected when the atrial refractory period is shortened, because the 2/1 point is increased. This objective can be achieved by greatly reducing atrioventricular delay (AVD) on exercise. Are such variations (up to 100-120 ms) detrimental from a haemodynamic standpoint? This study was performed to analyse this particular aspect of DDD pacing. Three DDD pacing modes, differing by their AVDs (fixed 200 ms AVD, fixed 150 ms AVD, and rate-adapted AVD) were tested in random order, with a haemodynamic protocol including ten patients with chronic atrio-ventricular (A-V) block. For the rate-adapted AVD pacing mode, AVD was reduced by 20 ms every 10 beats min-1 increment (from 220 ms at 90 beats min-1 to 100 ms at 150 beats min-1). Pacing rate was increased from 90 to 150 beats min-1 by increments of 10 beats min-1 every 5 min. Cardiac performance was significantly improved with the rate-adapted AVD above the two fixed AVDs, despite a large AVD variation. When AVD was rate adapted, cardiac index, stroke volume index and left ventricular systolic work index were generally higher and pulmonary capillary wedge pressure, pulmonary arterial pressure and systemic vascular resistances were generally lower, especially at 120, 130 and 140 beats min-1. Comparing the two fixed AVDs, 200 AVD improved cardiac function more at lower heart rates, whereas 150 AVD improved cardiac function more at higher heart rates. Despite its limitations, this study demonstrates that the potential benefits of reducing AVD with increasing heart rates should be twofold in dual chamber pacing: (a) haemodynamic, optimizing cardiac performance on exercise for all heart rates, especially in cases of organic heart disease; (b) electrophysiologic, permitting a sufficiently rapid maximal tracking rate in cases with long post-ventricular atrial refractory periods, allowing a satisfactory level of exercise.

Failure of the exercise test to predict the anterograde refractory period of the accessory pathway in Wolff Parkinson White syndrome.

Modifications of the delta wave on the surface ECG during an exercise stress test were compared to electrophysiological variations in accessory pathway (AP) refractoriness and in AV node conduction, during intravenous isoproterenol infusion in ten patients with WPW syndrome. In one patient, the delta wave persisted unchanged at the end of exercise and, with isoproterenol, there was a greater reduction in the AP anterograde effective refractory period (AERP) than in AV node conduction time. In three patients, the delta wave became less and less apparent but without completely disappearing; in these patients, the slight reduction of the AERP in the accessory pathway with isoproterenol was comparable to the reduction in AV node conduction time, explaining the progressive fusion between the two activation fronts. In the six other patients, the delta wave completely disappeared during exercise: in two cases, suddenly from one cycle to the next with strong concordance between the measured (isoproterenol) and the estimated (exercise test) AERP in the AP; in four cases, the disappearance was progressive with a significantly greater reduction in the AV node conduction time than in the measured AERP of AP which was nonetheless very short, 190 to 225 ms, during isoproterenol infusion. These findings confirm the limitations of the exercise test to predict the AERP of the AP. In addition, they demonstrate that modifications in the delta wave during exercise result from a balance between the relative effects of sympathetic stimulation on refractoriness of AP and normal AV conduction.

Critical analysis of cineangiographic criteria for diagnosis of arrhythmogenic right ventricular dysplasia.

Biplane 30-degree RAO and 60-degree LAO RV selective cineangiography was performed in 21 patients with significant ventricular arrhythmias (ventricular tachycardia in 14, salvos in three, and complex PVCs in seven) and a high presumption of arrhythmogenic RV dysplasia (ARVD), and in a control group of 10 presumed normal individuals. Comparing the two series revealed the lack of specificity of some angiographic images usually reported as suggestive signs of ARVD, such as slow dye evacuation of RV during the levophase and deep fissuring in the anterior wall with a "pile of plates" image. Inversely, localized morphologic and contraction abnormalities in the RV free wall were more sensitive and specific signs for diagnosis of ARVD; these were localized akinetic or dyskinetic bulges sometimes giving a true image of aneurysm (90%), wide and deep fissuring of the apex or of the inferior wall (33%), and large areas of akinesia. By order of frequency, these abnormalities were found on the apex in 71%, on the inferior wall in 52%, on the anterior wall in 48%, in the subtricuspid area in 38%, and on the pulmonary infundibulum in 33%. These localized lesions can suffice for the diagnosis of RV dysplasia in the absence of associated pathologies, such as ischemic heart disease or congenital defects. Usually a global RV systolic dysfunction is associated in ARVD, as confirmed by greater RV volumes (134 +/- 26 vs 79 +/- 10 ml/m2 for RVEDV, p less than 0.001; 76 +/- 34 vs 32 +/- 6 ml/m2 for RVESV, p less than 0.001), and lower RV ejection fraction (58 +/- 18% vs 47 +/- 8%, p less than 0.001) in the ARVD group compared to controls. Nevertheless, normal RV volumes and ejection fraction can be observed in some localized forms with mono- or bisegmental lesions in which RV systolic dysfunction is absent or moderate, and extensive forms with multiple segmental lesions where RV systolic dysfunction is constant and often severe. Six out of 21 patients in the ARVD group exhibited obvious global or segmental LV dysfunction, indicating the possibility of biventricular forms, as previously reported in other publications.

[Mid-term outcome of acute right ventricular dysfunction in biventricular myocardial infarction. Hemodynamic and cineangiographic studies]. / Devenir à moyen terme de la dysfonction aiguë du ventricule droit dans les infarctus du myocarde biventriculaires. Etude hémodynamique et cinéangiographique.

This study was designed to evaluate the mid-term outcome of the right ventricular (RV) dysfunction which characterizes infarction of both ventricles in the acute phase. Thirteen patients hospitalized for inaugural posterior or infero-posterior infarction extending to the right ventricle (haemodynamic and cineangiographic diagnosis) were explored in the acute phase and 4 months later by right heart catheterization and selective cineangiography of the right ventricle in a 30 degrees RAO projection. The results were compared with those obtained in a control group. Haemodynamically, the RV filling pressures (p less than 0.001) and the indices of RV dysfunction--i.e. RV end-diastolic pressure/RV systolic pressure ratio (p less than 0.001) and right atrial pressure/pulmonary wedge pressure ratio (p less than 0.02)--were significantly decreased between the acute and chronic phases, but they remained pathological compared with those measured in the control group. Angiographically, the right ventricular dysfunction in the acute phase was reflected in an increase of the RV end-systolic volume (p less than 0.02) and a decrease of the RV ejection fraction (p less than 0.01), whereas diastolic cavitary dilatation was inconstant, with mean values of RV end-diastolic volume close to those found in the control group. The systolic dysfunction persisted, unchanged, during the chronic phase. Segmental kinetics of the inferior wall was much reduced in the acute phase (p less than 0.001), this hypokinesia partially regressing in the chronic phase; but in fact there were wide individual variations, and some patients even recovered an almost normal contractility. Tricuspid valve regurgitation was frequent (6/13 cases) in the acute phase and regressed in 2 out of 3 cases in the chronic phase; its presence introduced a degree of bias in the measurement of RV end-systolic volume and RV ejection fraction, with a tendency to underestimate the severity of diastolic dysfunction. To summarize, right ventricular dysfunction was constant but often modest in the acute phase and remained relatively stable at mid-term, whereas segmental kinetics of the inferior wall improved, sometimes dramatically.

[Measurement of right ventricular volume by cineangiography. Validation of monoplane analysis compared with biplane]. / Mesure des volumes ventriculaires droits par la cinéangiographie. Validation de l'analyse monoplan comparée au biplan.

It is demonstrated that right ventricular volumes can be measured accurately by biplane cineangiography using the Simpson's rule or various area-length methods. In order to validate the single plane approach a biplane (30 degrees RAO-60 degrees LAO) right ventricle (RV) cineangiography was performed in 10 adults investigated for chest pain without coronary artery disease or any other heart disease. RV volumes (EDV: end-diastolic; ESV: end-systolic; SV: stroke volume) and EF (ejection fraction) were measured by biplane and single plane analysis with the same area-length method using the pyramide with triangular base as geometric model (Ferlinz). The results are: RVEDV (ml/m2) biplane (B) 81 +/- 10, monoplane (M) 82 +/- 11; RVESV (ml/m2) B 33 +/- 6, M 35 +/- 8; RVSV (ml/m2) B 48 +/- 8, M 47 +/- 10; RVEF (%) B 59 +/- 6, M 57 +/- 8. Equations of linear regression show the following correlations: RVEDV R = 0.82 p less than 0.01; RVESV R = 0.77 p less than 0.01; RVSV R = 0.92 p less than 0.001; RVEF R = 0.85 p less than 0.01. Authors conclude to a good enough correlation between monoplane and biplane analysis especially for RVSV and RVEF. They underline the great variability of individual values.

Physiological relationship between AV interval and heart rate in healthy subjects: applications to dual chamber pacing.

The purpose of this paper is to specify the mathematical relationship between spontaneous AV interval (AVI) and heart rate (HR), the amplitude and rate of variation of AVI, and the physiological factors likely to affect these characteristics. Ten patients with healthy hearts were studied. Two catheter electrodes were positioned in the right atrium and at the tip of the right ventricle respectively, allowing the detection of endocardial signals. The AV and AA intervals for each heart cycle were digitized to an accuracy of +/- 1 msec. Measurements were made at rest, then during a stress test on an exercise bicycle, and finally during the recovery phase. The results show that adaptation is very precise and takes place instantly. Any variation in heart rate causes an immediate, inversely proportional variation in AVI. Adaptation follows a linear pattern, generally with relatively low amplitude and an average AVI reduction of 27.5 +/- 11.2 msec for an average HR increase of 78.7 +/- 22.5 bpm, i.e., a decrease of 4 +/- 2.1 msec for an HR variation of 10 bpm. The amplitude and variation rate of AVI seem to be independent of the age and base value of the PR interval. These observations may be useful for designing new VDD or DDD pacemakers that automatically adapt the AV interval to the instantaneous heart rate. The hemodynamic benefits of this adaptation were also demonstrated.

[Surgical correction of chronic tricuspid insufficiency following infarction of the right ventricle]. / Correction chirurgicale d'une insuffisance tricuspidienne chronique secondaire à un infarctus du ventricule droit.

The case of a 69 year old man with isolated tricuspid regurgitation secondary to right ventricular infarction is reported. The poor long-term tolerance of the regurgitation resulting in severe right ventricular failure in the absence of any left ventricular dysfunction led to tricuspid valve replacement with a bioprosthesis 13 years after the causal infarct.

[Severe hypoxemia due to a right-to-left shunt at the atrial level caused by an infarction of the right ventricle]. / Hypoxémie sévère par shunt droite-gauche à l'étage auriculaire lié à un infarctus du ventricule droit.

The authors report the case of a biventricular inferior myocardial infarction complicated in the acute phase by massive tricuspid regurgitation and a right-to-left interatrial shunt through a patent foramen ovale; this resulted in severe hypoxaemia. The diagnosis was made by contrast 2D echocardiography which showed ventriculo-atrial regurgitation and the passage of microbubbles from the right to the left atrium leading to opacification of the left ventricule: right heart catheterisation with oxymetry and selective right ventriculography confirmed the diagnosis. The hypoxaemia became less severe as the haemodynamic conditions improved. This is one possible mechanism of severe hypoxaemia in the acute phase of myocardial infarction and should be excluded routinely in this situation as it can have important prognostic and therapeutid implications.

[Tricuspid insufficiency in biventricular myocardial infarct]. / L'insuffisance tricuspidienne des infarctus du myocarde biventriculaires.

Tricuspid insufficiency (TI) has already been reported as a possible complication of biventricular infarction. However, in the absence of large study groups, this condition is not well known. This paper reports the results of 2 studies: a retrospective study of 91 biventricular infarcts, identified by haemodynamic criteria, and a prospective study of 23 consecutive patients (belonging to the previous group) in whom selective right ventricular cineangiography was performed in the acute phase. The following conclusions were drawn: moderate to severe TI is very common during the first days of infarction (30%/39%); the diagnosis is simple, based on non invasive, very sensitive (89%) and specific (100%) haemodynamic criteria; it is associated with a much more severe clinical and haemodynamic presentation and with a higher mortality in the acute phase (37% vs 6.2% in the global study); the poor prognosis does not persist in the long term; regression is common (2/3 to 3/4 of cases) and angiographic data suggests that it is often related to a transient ischaemic papillary muscle dysfunction. Acute paralysis of the right atrium may also play a major role; the TI remains unchanged only in rare cases and may then be responsible for a chronic right ventricular dysfunction and then raise the question of surgical intervention.

[Infarction of the right ventricle]. / Les infarctus du ventricule droit.

Anatomical studies have confirmed that isolated right ventricular and anterior biventricular infarcts are rare. However, RV extension is found in 36 to 50 per cent of cases of postero-inferior infarcts, which confirms the findings of invasive and non-invasive investigations which detect acute RV dysfunction with the same frequency after this type of infarct. It is difficult to create right ventricular infarction experimentally because of the relative protection against ischaemia of the RV. In man, this condition almost always implies an associated thrombosis of the proximal right coronary artery and significant stenosis of the IVA, which justifies the broad indications for coronary angiography. The two major haemodynamic consequences of right ventricular infarction are due to original pathophysiological mechanisms: the adiastole seems to be due to a limitation of RV dilatation by the pericardium, the reduced output is due to faulty LV filling as a result of RV systolic dysfunction and associated factors such as the absence of efficient and synchronous atrial systole secondary to AVB (60%) or to acute right atrial paralysis. The choice of treatment is based on these pathophysiological data. The diagnosis of infarction of the RV is straightforward, often suggested on clinical examination (RVI syndrome: reduced output in 45% of cases) and the surface E.C.G. (ST-T depression 1 mm in V3R-V4R-V5R). The diagnosis is confirmed by more sophisticated investigations which can evaluate the degree of systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

[M-mode echocardiographic study of right ventricular involvement in the acute phase of inferoposterior myocardial infarction]. / Etude échocardiographique TM de l'atteinte ventriculaire droite à la phase aiguë des infarctus du myocarde inféro-postérieurs.

The aim of this study was to assess the value of a non-invasive technique, echocardiography, in diagnosing RV extension during the acute phase of myocardial infarction. Forty patients with an acute infero-posterior infarct were divided into two groups according to the presence (Group A) or absence (Group B) of RV akinesia on angiography. M mode echocardiography was carried out from two positions: left parasternal, for the study of quantitative parameters: RV and LV diameters, wall thickness and excursion, VCF and fractional shortening, mitral and tricuspid valve morphology, aortic and left atrial dimensions; subxostal: for the study of one parametere: RV inferior wall motion assessed as normal or akinetic. A comparative statistical study including a group of 35 controls was carried out. The results showed at comparable values in both groups, that patients in Group A had lower global LV function, hypokinesia of the LV posterior wall with minor changes in the mitral valve echo and LA dimension; akinesia of the RV inferior wall, a direct and specific sign of RV infarction, was observed in 50 p. 100 of cases; in comparison with the other two groups, despite large individual variations, there was a significant increase in RV diameter (p less than 0,001) and RV/LV diameter (p less than 0,001), and in the amplitude of systolic motion of the RV anterior wall (p less than 0,05 and p less than 0,01). Other qualitative signs were inconstant: paradoxical septal motion (7/20), pericardial separation (3/20), tricuspid B point (5/20). Dilatation of the RV was inconstant (50 p. 100 of cases) but its association with paradoxical septal motion was indicative of significant tricuspid incompetence. Akinesia of the RV inferior wall seemed to be of prognostic value: RVEDP and the extent of angiographic RV akinesia were greater in its presence (p less than 0,05). There was a slight correlation between RV dimensions (RV diameter and RV/LV diameters) and the extent of angiographic RV akinesia (R = 0,50, p less than 0,05) and with cardiac index (R = 0,60, p less than 0,05). This study shows that M mode echo provides positive direct signs of RV infarction in about 50 p. 100 of cases. The sensitivity of the technique is therefore relatively low. However, it does distinguish the more severe forms of biventricular infarction, especially when complicated by tricuspid incompetence.

[Detachment of valve prostheses. Apropos of 24 cases]. / Désinsertions de prothèses valvulaires. A propos de 24 cas.

A series of 24 cases of paraprosthetic valvular regurgitation, 10 mitral and 14 aortic, in 19 out of a group of 634 operated patients with a total of 822 prosthetic heart valves is reported. The presenting features are dominated by auscultatory changes, though inconstant episodes of heart failure, and, in aortic prostheses, the high incidence of infective endocarditis. Paraclinical investigations are of variable value; cineradiography in aortic valves and phonocardiography in mitral valves are useful; catheterisation with ventriculography or aortic angiography according to the case under study are the investigations of choice, especially in mitral regurgitation where it is essential. Typical clinical settings for these problems are valve ring dilatation calcification, and previous or active infective endocarditis. The indications for urgent surgery depend on the clinical signs, the presence of heart failure, haemolysis, active endocarditis and deterioration despite medical treatment. The series compares the data in mitral paraprosthetic regurgitation, difficult to diagnose but with a reasonably good prognosis, and aortic paraprosthetic regurgitation, easier to diagnose but associated with a poor prognosis due to the high incidence of associated endocarditis.