Symptoms during ATP-test under pacing: impact on syncope recurrence and prediction from the ATP-test without pacing.

Syncope recurrence in patients with positive ATP-test who underwent permanent pacemaker implantation is suspected to be related to vagal vasodilatation. We studied symptoms during ATP-test in 38 temporary paced patients. Among patients with positive ATP-test who underwent permanent pacemaker implantation (N = 14), the only one patient who recurred during follow-up was symptomatic during the initial paced ATP-test. Symptoms during paced ATP-test were well predicted by a higher blood pressure (BP) drop during standard ATP-test (i.e. without pacing) (Area under ROC curves > 0.70 for all BP parameters except for relative diastolic BP drop). Moreover, BP drop during standard and paced ATP-test were significantly correlated (all p ≤ 0.03). Thus, a higher BP drop measured during ATP-test without pacing might help identify patients who would experience recurrences due to vasodilatation under permanent pacing.

Blood pressure drop and symptoms during ATP-test under pacing.

We studied systolic blood pressure (SBP) behavior and symptoms during ATP-test in temporary paced patients. SBP drop during ATP-test is only partially prevented by pacing. During DDD paced ATP-test, SBP minimum was lower in symptomatic patients. Considering the role of endogenous adenosine in neurally-mediated syncope (NMS), our results are concurrent with a SBP fall resulting in NMS recurrence under permanent pacing.

[The adenosine-5'-triphosphate (ATP) test: a diagnostic tool in the management of syncope of unknown origin. Basic and clinical aspects]. / Apport du test à l'adénosine-5'-triphosphate (ATP) dans l'évaluation diagnostique et l'approche therapeutique des syncopes d'origine indéterminée (vasovagale ou neurocardiogénique).

The prevalence of syncope increases in elderly population. An inappropriate reflex reaction of the autonomous nervous system in specific circumstances is responsible for symptoms in more than 50% of cases. These neurocardiogenic or vasovagal syncopes are due to a vasoplegia or to a cardio-inhibitory reflex or to the association of both mechanisms. Reproducing the symptoms may contribute to identify the responsible mechanism of syncope; this objective is partly reached by the head-up tilt test--a provocative test--which reproduces symptoms in about half of the cases, mainly by provoking a severe vasodilation with fall of blood pressure. On the opposite, the ATP test (20 mg i.v. bolus)--a descriptive test--provokes a strong cardio-inhibitory reflex independent from external factors like body position but it must be undertaken in a calm environment for preventing any anticipative sympathetic reaction. The test is considered positive if ATP produces a cardiac pause longer than 10 seconds and related symptoms are not taken into account for assessing the final result. ATP test positivity increases with age and with the presence of cardiac diseases. Permanent dual chamber pacing at 70 bpm has been shown to reduce significantly the syncope recurrences in patients with positive ATP test and to have no influence on patients with a negative test. The use of ATP test should be extended to all syncope screening. Its positivity identifies a group of patients in whom the mechanism of the syncope is susceptible to be improved by a permanent dual chamber pacing.

Contribution of head-up tilt testing and ATP testing in assessing the mechanisms of vasovagal syndrome: preliminary results and potential therapeutic implications.

BACKGROUND: In patients with vasovagal syndrome, head-up tilt testing may reproduce symptoms generally associated with vasodepression. Recent research suggests ATP testing identifies patients with abnormal vagal cardiac inhibition. This preliminary study examined the joint contribution of both tests in identifying underlying mechanisms in the general population with vasovagal syndrome. METHODS AND RESULTS: Both tests were performed in random order during 1 session and outside of predominant sympathetic periods in 72 patients hospitalized for syncope (n=56) or presyncope (n=16) for whom no cardiac or extracardiac cause was found. For passive and isoproterenol-provocative tilt testing by standard protocol, reproduction of symptoms defined a positive test. The ATP test consisted of injecting ATP 20 mg IV at bedside, continuously monitoring ECG and blood pressure; a vagal cardiac pause >10 seconds defined a positive test. For most patients (64%), >/=1 test was positive. Of the 41 patients (57%) with a positive tilt test (either passive or provoked by isoproterenol), 32% had cardiac disease; none had significant bradycardia (<50 bpm). Of the 8 patients (11%) with a positive ATP test, 62% had cardiac disease; the probability of a positive result increased with age (P=0.015). Both tests were positive in 3 patients and negative in 26 patients; the tilt and ATP test results were uncorrelated (P=0.28). CONCLUSIONS: Results suggest tilt and ATP tests individually and jointly determine the mechanism of vasovagal symptoms in most patients and that vagal cardiac inhibition increases with age.

Is a pacemaker indicated for vasovagal patients with severe cardioinhibitory reflex as identified by the ATP test? A preliminary randomized trial.

BACKGROUND: A previous observational study suggested that, in syncopal elderly patients with vasovagal syndrome, a test using adenosine-5'-triphosphate (intravenous ATP 20 mg. 2 ml-1) could identify a subgroup of patients at high risk of severe cardioinhibitory response and guide the therapeutic strategy. To test one aspect of these results prospectively, we designed a small study focusing only on vasovagal patients with abnormal response to ATP testing. METHODS: Twenty patients hospitalized for syncope, which was considered to be vasovagal, and exhibiting an abnormal ATP test--defined by a longer than 10 s cardiac pause--were randomized to two groups: half to implantation with a dual-chamber pacemaker and half to usual medical care. All patients who were not hospitalized for recurrences were assessed every 6 months in the clinic or by telephone. RESULTS: At baseline, the randomized patient groups were similar in their demographic and health characteristics and in the results of their ATP tests, for example the mean cardiac pause (21.4 +/- 9.3 vs 15.9 +/- 3.7 s) and the mean interval between escape beats during the pause (7.29 +/- 4.2 vs 7.48 +/- 3.3 s). During a mean follow-up of 52 months, recurrences appeared in six of the 10 usual-care patients (range 0.2-29 months) but in none of the implanted patients (P < 0.02). CONCLUSIONS: This limited trial (1) supports the conclusion that patients with an abnormal ATP test who receive a dual-chamber pacemaker suffer fewer recurrences than those who are monitored only; and (2) consequently further supports the hypothesis that, among vasovagal patients, a cardiac pause of longer than 10 s in patients administered ATP identifies those at high risk of symptomatic vagal cardiac inhibition.

Reproducibility of the adenosine-5'-triphosphate test in vasovagal syndrome.

INTRODUCTION: Adenosine-5'-triphosphate (ATP) provokes negative chronotropic and dromotropic vagal effects. In vasovagal syndrome, ATP test (20-mg i.v. bolus infusion) represents a promising technique for identifying patients at risk of severe cardioinhibitory response of vagal origin. The electrocardiographic and related symptom reproducibility of this descriptive test must be assessed. METHODS AND RESULTS: In order to achieve this objective, ATP tests were performed twice in 80 patients (44 men, 36 women; mean age 72.3+/-12.2 years) by using the recently published test procedure and criteria of positivity. The second test was repeated shortly after the initial test (mean: 7 days) in 43 patients and long-term (mean: 3.7 years) in 37 patients. The initial ATP test provoked a cardiac pause > 10 seconds in 31 patients (39%) and a short cardiac pause (< or =10 sec) or no pause in 49 patients (61%). The electrocardiographic outcome was reproduced during the second ATP test in 36 patients (84%) of the short-term group and in 29 patients (78%) of the long-term group. Similarly, symptoms were reproduced in 38 patients (88%) of the short-term group and 29 patients (78%) of the long-term group, reflecting the severity of the electrocardiographic outcome. CONCLUSION: The negative chronotropic and dromotropic vagal effect of ATP can be reproduced short term and long term in 84% and 78% of patients, respectively. Associated symptoms were related to the severity of the electrocardiographic outcome.

Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial.

BACKGROUND: The pathogenesis of unstable angina and non-Q-wave myocardial infarction is still poorly understood, and early evaluation of prognosis remains difficult. We therefore studied the predictive value of 5 biological indicators of inflammation, thrombogenesis, vasoconstriction, and myocardial necrosis, and we examined the effects of enoxaparin and unfractionated heparin on these markers after 48 hours of treatment. METHODS AND RESULTS: Sixty-eight patients with unstable angina or non-Q-wave myocardial infarction randomized in the international ESSENCE trial participated in this French substudy. C-reactive protein, fibrinogen, von Willebrand factor antigen, endothelin-1 and troponin I were measured on admission and 48 hours later. The composite end point of death, myocardial infarction, recurrent angina, or revascularization was significantly lower at 14 and 30 days of follow-up in patients allocated to enoxaparin compared with unfractionated heparin. All acute-phase reactant proteins were elevated on admission and increased further at 48 hours. Multivariate analysis demonstrated that the rise of von Willebrand factor over 48 hours was a significant and independent predictor of the composite end point at both 14 days and 30 days. Moreover the early increase of von Willebrand factor was more frequent and more severe with unfractionated heparin than with enoxaparin (mean change was +8.7+/-8.8% with enoxaparin versus +93.9+/-11.7% with unfractionated heparin, P<0.0001). The other clinical and biological variables did not predict outcome. CONCLUSIONS: In patients with unstable angina or non-Q-wave myocardial infarction, the acute-phase proteins increase over the first 2 days despite medical treatment. The early rise of von Willebrand factor is an independent predictor of adverse clinical outcome at 14 days and at 30 days. Enoxaparin provides protection as evidenced by the reduced release of von Willebrand factor, which represents a favorable prognostic finding.

[A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia]. / Etude randomisée en double aveugle comparant la cibenzoline et le disopyramide dans la prévention de récidives de tachyarythmies atriales.

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.

Can adenosine 5'-triphosphate be used to select treatment in severe vasovagal syndrome?

BACKGROUND: Selection of treatment in vasovagal syndrome should be guided by the mechanism of symptoms. This study determined whether a simple drug test may assess one mechanism. METHODS AND RESULTS: To identify patients at risk of severe cardioinhibitory response of vagal origin, we infused 20 mg ATP into 316 patients hospitalized for recurrent syncope (n=195) or presyncope (n=121) of unknown origin and into normal subjects (n=51). We then assessed the ECG and clinical responses to the drug, recommended therapy, and followed up the subjects chronically. A cardiac pause > 10 seconds was seen in only 3 normal subjects (6%). Therefore, a pause < or = 10 seconds yielded the approximately 95th percentile of the normal range. ATP provoked a pause > 10 seconds in 130 symptomatic patients (41%) and a pause < or = 10 seconds in 186 symptomatic patients (59%). Thus, symptomatic patients with pauses > 10 seconds were proposed for pacemaker implantation; all other patients and normal subjects were simply monitored. Among long-pause patients with follow-up, the observed recurrence rate for the 104 with pacemakers was one-third that for the 21 who were only monitored (P<.0001). Among followed-up short-pause patients, the rate in the 153 monitored-only patients did not differ from the 20 implanted patients (P=.432). CONCLUSIONS: The vagal effect of ATP may identify the subgroup of patients at high risk of severe cardioinhibitory response of vagal origin who likely will benefit from pacemaker therapy. This fast, uncomplicated test should be considered for further use in screening patients with vasovagal syndrome.

Acute and long-term efficacy of perindopril in severe chronic congestive heart failure.

To assess the short- and long-term hemodynamic efficacy of perindopril, 15 patients (12 men and 3 women) diagnosed with congestive heart failure were treated with oral perindopril (4 mg daily) for 3 months in association with digitalis and diuretic maintenance therapy. Patients were in New York Heart Association (NYHA) functional classes III and IV. Underlying cardiopathy was ischemic (6 patients), hypertensive (5 patients), valvular (2 patients), and dilated cardiomyopathy (2 patients). Hemodynamics, angiotensin-converting enzyme (ACE) activity, and perindoprilat (the active metabolite of perindopril) blood titration were measured at 2 periods. Acute assessment was performed over 2 titration days on oral perindopril 2 mg (day 1) and 4 mg (day 2); measurements were performed at rest and at 0, 1, 4, 6, 8, 12, and 24 hours. Chronic assessment was performed after 3 months of treatment with oral perindopril, 4 mg daily. During the study, 1 patient withdrew due to low systolic blood pressure (< 100 mm Hg) and 3 severely impaired patients died due to a worsening of heart failure during the study. Among the 11 remaining patients, 6 were symptomatically improved. On 4 mg perindopril administration, hemodynamic improvement was similar for peak values at both day 2 and at 3 months. At day 2, compared with baseline, cardiac index increased by 21% (p < 0.05) and pulmonary capillary wedge pressure (PCWP) and mean arterial pressure (MAP) decreased by 54% and by 21%, respectively (p < 0.01). Similarly, at 3 months, cardiac index increased by 37% (p < 0.001) and PCWP and MAP decreased by 41% and 19%, respectively (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Interstitial pulmonary involvements in polymyositis and dermatopolymyositis. Apropos of 3 cases. Review of the literature]. / Atteintes pulmonaires interstitielles des polymyosites (PM) et dermatopolymyosites (DP). A propos de 3 observations. Revue de la littérature.

The authors report 3 cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jol antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.

Amplitude and direction of atrial depolarization using a multipolar floating catheter: principles for a single lead VDD pacing.

VDD stimulation using a single catheter for atrial sensing and ventricular sensing and pacing has become a reality. In order to compare the quality of the cavitary atrial electrogram (AEG) and to determine the intraatrial P wave direction and conduction time (CT), we compared, in an acute study, three different types of atrial electrode systems using four different leads, in 53 patients in sinus rhythm. The three electrode systems were: (1) one experimental system with quadripolar orthogonal electrodes using the Goldreyer concept; (2) one experimental system with quadripolar whole ring electrodes; (3) two systems with diagonally oriented half-ring electrodes, one experimental quadripolar and one bipolar CCS commercial (Polysafe A-Track lead). For the experimental systems, the four electrodes forming two independent bipolar pairs were situated on the intraatrial floating portion of a single lead and one supplemental electrode was distally positioned in the right ventricular apex. Bipolar AEGs were recorded at the high and at the low levels of the right atrium. For the CCS lead, the single bipolar AEG was recorded at the high level of the right atrium only. The highest AEG amplitude and the highest values for ventricular far-field rejection were provided by both diagonally oriented half-ring electrodes at the high atrial level and by the whole ring electrodes at the low atrial level. For both atrial levels, the orthogonal electrode system provided the smallest AEG amplitudes, the highest ventricular electrogram amplitudes, and therefore, the smallest values for ventricular far-field rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Interstitial pulmonary involvement of polymyositis and dermatomyositis. Apropos of 3 cases. Review of the literature]. / Atteintes pulmonaires interstitielles des polymyosites (PM) et dermatopolymyosites (DP). A propos de 3 observations. Revue de la littérature.

The authors report 3 new cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti-Jo1 antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis.

[Intravenous enoximone versus conventional treatment in acute lung edema. Preliminary results of a randomized study]. / Enoximone administré par voie intraveineuse contre traitement conventionnel dans l'oedème aigu du poumon. Résultats préliminaires d'une étude randomisée.

The aim of this open study was to compare the efficacy of Enoximone and conventional treatment in 44 patients with acute pulmonary edema. At the time of this interim analysis, 22 patients had received Enoximone (1 mg/kg by rapid intravenous injection every 8 hours for 48 hours) and 22 were given conventional treatment (furosemide, nitrates, dopamine-dobutamine). The treatment schedules were randomised. Clinical data was obtained at 0, 1, 2, 24 and 48 hours and evaluated using the Killip-Kimball score, dyspnoea, pulmonary rales, the need for additional therapy and patient mortality. The patients in the two groups were comparable in all clinical features except the sex ratio. The improvement of all clinical criteria of evaluation seemed to be greater in the Enoximone group, except during the first hour of treatment (due to the action of diuretics). The overall outcome was better in the Enoximone group (17 favourable responses compared to 11 in the group receiving conventional treatment). Normalisation of haemodynamic parameters was observed only with Enoximone. In addition, it became necessary to administer Enoximone to 9 patients in the conventional treatment group. At these doses, Enoximone was at least as effective as conventional treatment of acute pulmonary edema. What is more, no secondary effects or tachyphylaxis were observed during the period of hospital treatment.

Acute pulmonary oedema: preliminary results of a randomized trial of the intravenous phosphodiesterase inhibitor, enoximone, vs conventional therapy.

The purpose of this open study was to compare the effects of enoximone and conventional therapy in 44 patients with acute pulmonary oedema. In this preliminary report, 22 patients were randomly assigned to the enoximone group (1 mg/kg bolus, every 8 hours for 48 hours) and 22 patients to conventional therapy (frusemide, nitrates, dopamine-dobutamine). Patients were assessed clinically at 0, 1, 2, 24 and 48 hours by the change in their Killip-Kimball score, dyspnoea, pulmonary rales, blood pressure, diuresis, requirement for additional therapy and/or death. Patient characteristics were similar except for distribution of the sexes. Improvements of each clinical parameter seemed more marked in the enoximone group, except during the first hour (due to the diuretics). The general course of the disease was more favourable in the enoximone group (17 cases vs 11 in the conventional therapy group), in which enoximone used alone was sufficient to normalize the haemodynamic variables. On the other hand, in the conventional therapy group, it was necessary to institute enoximone therapy in 9 cases. With the dosage used, enoximone appeared to be at least as effective as conventional therapy in acute pulmonary oedema. Moreover, no side-effects or tachyphylaxis appeared during the hospital assessment.

[Acute thrombosis of mitral Starr prosthesis. Value of color coded two-dimensional doppler echocardiography]. / Thrombose aiguë de prothèse de Starr mitrale. Intérêt de l'échocardiographie-doppler bidimensionnelle à codage couleur.

In a case of acute thrombosis on mitral Starr valve two-dimensional doppler-echocardiography rapidly showed that parts of the transprosthetic jets had disappeared, while conventional continuous wave doppler ultrasound confirmed the presence of a severe haemodynamic obstacle. With colour-coded doppler ultrasound, there only remained a jet that was parallel to the posterior wall of the left ventricle. This jet was of unusual pattern, with the presence of turbulence and high velocities in aliasing colour. The effectiveness of a thrombolytic treatment was demonstrated by the reappearance of the missing diastolic jets with return to normal velocities. Comparison between a post-thrombolysis colour-coded doppler examination and a reference examination confirmed that the valve was now functioning normally. Thus, while conventional doppler recordings accurately quantify prosthetic dysfunctions leading to stenosis, two-dimensional doppler recordings rapidly provide an anatomical information. By showing changes in the transprosthetic jets they indicate the precise location and extent of valve obstruction.

Myocardial infarction: is bepridil, a new calcium antagonist, able to improve the course of the acute phase?

Several calcium antagonists are useful in the treatment of ischemic heart disease. This open randomized study was designed to determine the effects of bepridil, a new long-acting calcium antagonist with antiarrhythmic properties, on the course of acute myocardial infarction (AMI). Two hundred patients with AMI of less than 48 hours duration (average 10.9 hours) were randomly assigned to two treatment groups: The first one was treated with bepridil (BEP, n = 100), and the second one was considered as a control group, using isosorbide dinitrate at a low dosage (ISDN, n = 100). BEP was administered intravenously for 48 hours at a dosage of 4 mg/kg/day; at the same time, an oral dose of 200 mg t.i.d. was started and continued for 21 days. In the control group, ISDN was given orally at the low dosage of 5 mg every 4 hours for 21 days. An uneventful course was seen in 28 BEP patients versus 15 in the control group (p less than 0.05). Mortality and recurrence of angina were lower in the BEP group than in the control group, but the difference is not significant. On the other hand, moderate and severe hemodynamic complications did not occur in 80 BEP patients versus 65 in the control group (p less than 0.05). Ventricular arrhythmias occurred in 36 BEP patients versus 50 in the control group (p less than 0.05). Antiarrhythmic therapy was required in 14 BEP patients versus 61 in the control group (p less than 0.001). These results show that bepridil seems capable of improving the hemodynamics and arrhythmologic course of AMI.