Implantation of a novel insertable cardiac monitor: preliminary multicenter experience in Europe.

BACKGROUND: The LUX-Dx™ is a novel insertable cardiac monitor (ICM) introduced into the European market since October 2022. PURPOSE: The aim of this investigation was to provide a comprehensive description of the ICM implantation experience in Europe during its initial year of commercial use. METHODS: The system comprises an incision tool and a single-piece insertion tool pre-loaded with the small ICM. The implantation procedure involves incision, creation of a device pocket, insertion of the ICM, verification of sensing, and incision closure. Patients receive a mobile device with a preloaded App, connecting to their ICM and transmitting data to the management system. Data collected at European centers were analyzed at the time of implantation and before patient discharge. RESULTS: A total of 368 implantation procedures were conducted across 23 centers. Syncope (235, 64%) and cryptogenic stroke (34, 9%) were the most frequent indications for ICM. Most procedures (338, 92%) were performed in electrophysiology laboratories. All ICMs were successfully implanted in the left parasternal region, oriented at 45° in 323 (88%) patients. Repositioning was necessary after sensing verification in 9 (2%) patients. No procedural complications were reported, with a median time from skin incision to suture of 4 min (25th-75th percentiles 2-7). At implantation, the mean R-wave amplitude was 0.39 ± 0.30 mV and the P-wave visibility was 91 ± 20%. Sensing parameters remained stable until pre-discharge and were not influenced by patient characteristics or indications. Procedural times were fast, exhibited consistency across patient groups, and improved after an initial experience with the system. Operator Operator feedback on the system was positive. Patients reported very good ease of use of the App and low levels of discomfort after implantation. CONCLUSIONS: LUX-Dx™ implantation appears efficient and straightforward, with favorable post-implantation sensing values and associated with positive feedback from operators and patients.

Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs.

BACKGROUND: Atrial tachycardia-induced remodeling promotes the occurrence and maintenance of atrial fibrillation (AF) and decreases L-type Ca(2+) current. There is also a clinical suggestion that acute L-type Ca(2) channel blockade can promote AF, consistent with an AF promoting effect of Ca(2+) channel inhibition. METHODS: To evaluate the potential mechanisms of AF promotion by Ca(2+) channel blockers, we administered verapamil to morphine-chloralose anesthetized dogs. Diltiazem was used as a comparison drug and autonomic blockade with atropine and nadolol was applied in some experiments. Epicardial mapping with 240 epicardial electrodes was used to evaluate activation during AF. RESULTS: Verapamil caused AF promotion in six dogs, increasing mean duration of AF induced by burst pacing, from 8+/-4 s (mean+/-S.E.) to 95+/-39 s (P<0.01 vs. control) at a loading dose of 0.1 mg/kg and 228+/-101 s (P<0.0005 vs. control) at a dose of 0.2 mg/kg. Underlying electrophysiological mechanisms were studied in detail in five additional dogs under control conditions and in the presence of the higher dose of verapamil. In these experiments, verapamil shortened mean effective refractory period (ERP) from 122+/-5 to 114+/-4 ms (P<0.02) at a cycle length of 300 ms, decreased ERP heterogeneity (from 15+/-1 to 10+/-1%, P<0.05), heterogeneously accelerated atrial conduction and decreased the cycle length of AF (94+/-4 to 84+/-3 ms, P<0.005). Diltiazem did not affect ERP, AF cycle length or AF duration, but produced conduction acceleration similar to that caused by verapamil (n=5). In the presence of autonomic blockade, verapamil failed to promote AF and increased, rather than decreasing, refractoriness. Neither verapamil nor diltiazem affected atrial conduction in the presence of autonomic blockade. Epicardial mapping suggested that verapamil promoted AF by increasing the number of simultaneous wavefronts reflected by separate zones of reactivation in each cycle. CONCLUSIONS: Verapamil promotes AF in normal dogs by promoting multiple circuit reentry, an effect dependent on intact autonomic tone and not shared by diltiazem.

Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs.

BACKGROUND: Tachycardia-induced remodeling likely plays an important role in atrial fibrillation (AF) maintenance and recurrence after cardioversion, and Ca(2+) overload may be an important mediator. This study was designed to evaluate the relative efficacies of selective T-type (mibefradil) and L-type (diltiazem) Ca(2+)-channel blockers in preventing tachycardia-induced atrial remodeling. METHODS: Dogs were given daily doses of mibefradil (100 mg), diltiazem (240 mg) or placebo in a blinded fashion, beginning 4 days before and continuing through a 7-day period of atrial pacing at 400 bpm. An electrophysiological study was then performed to assess changes in refractoriness, refractoriness heterogeneity and AF duration. RESULTS: Mean duration of burst-pacing induced AF was similar in placebo (567+/-203 s) and diltiazem-treated (963+/-280 s, P=NS) animals, but was much less in mibefradil-treated dogs (3.6+/-0.9 s, P<0.002) and non-paced controls (6.6+/-2.7 s). In contrast to mibefradil, diltiazem did not alter tachycardia-induced refractoriness abbreviation or heterogeneity. To exclude inadequate dosing as an explanation for diltiazem's inefficacy, we studied an additional group of dogs treated with 720 mg/day of diltiazem, and again noted no protective effect. Acute intravenous administration of diltiazem to control dogs failed to alter atrial refractoriness or AF duration, excluding a masking of remodeling suppression by offsetting profibrillatory effects of the drug. CONCLUSIONS: Whereas the selective T-type Ca(2+)-channel blocker mibefradil protects against atrial remodeling caused by 7-day atrial tachycardia, the selective L-type blocker diltiazem is without effect. These findings are potentially important for understanding the mechanisms and prevention of clinically-relevant atrial-tachycardia-induced remodeling.

[Acute dissection of the ascending thoracic aorta complicated by myocardial infarct: an unavoidable diagnostic pitfall?]. / Dissection aiguë de l'aorte thoracique ascendante compliquée d'infarctus du myocarde: un piège diagnostique inévitable?

BACKGROUND: Acute dissection of the aorta during myocardial infarction is exceptional. In such cases, fibrinolysis can be fatal. CASE REPORTS: A 63-year-old woman with a history of hypertension was referred to our intensive care unit with the diagnosis of early stage inferior myocardial infarction. Thrombolysis was instituted and the patient rapidly developed cardiovascular collapse with global heart failure. Coronarography was attempted to revascularize the occluded coronary artery but the coronary arteries could not be catheterized. An aortography was performed and gave the diagnosis of De Bakey type I dissection of the aorta. The patient died from cardiac arrest after a phase of low cardiac output. DISCUSSION: This case illustrates how myocardial infarction can complicate or mask acute dissection of the aorta. It also raises the question of transthoracic echocardiography prior to institution of fibrinolysis.

The T-type Ca(2+) channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs.

BACKGROUND: Ca(2+) overload is believed to play a role in tachycardia-induced atrial electrophysiological remodeling. L-type Ca(2+) channel blockers attenuate effective refractory period (ERP) changes caused by 24 hours of atrial tachycardia but may not substantially alter atrial fibrillation (AF) inducibility. This study assessed the effects of the T-type Ca(2+) channel blocker mibefradil on tachycardia-induced atrial remodeling. METHODS AND RESULTS: Dogs subjected to rapid atrial pacing (400 bpm) for 7 days were treated with mibefradil (100 mg/d, n=8) or matching placebo (n=10) in blinded fashion. Radiofrequency ablation of atrioventricular conduction and ventricular pacing were used to control ventricular rate. Placebo dogs showed significant decreases in atrial ERP (76+/-5 ms at a cycle length of 300 ms) and increases in ERP heterogeneity (27.7+/-2.4%), AF duration (414+/-232 seconds), and AF inducibility by single extrastimuli (41+/-10% of sites) compared with 10 unpaced control dogs (ERP 114+/-3 ms, ERP heterogeneity 13.8+/-0.9%, AF duration 7+/-3 seconds, AF inducibility 1.9+/-1.0% of sites). The changes caused by atrial tachycardia were strongly attenuated in mibefradil dogs, with ERPs averaging 102+/-7 ms, ERP heterogeneity 18.8+/-1.4%, AF duration 3+/-1 seconds, and AF inducibility 9.6+/-4.0% of sites. Among mibefradil-treated dogs, ERP, AF duration, and inducibility correlated with plasma drug concentration. Acute mibefradil administration did not alter ERP or AF. CONCLUSIONS: Mibefradil, a drug with strong T-type Ca(2+) channel blocking properties, prevents AF-promoting electrophysiological remodeling by atrial tachycardia. These findings have important potential implications for the mechanisms of tachycardia-induced atrial remodeling and demonstrate the feasibility of preventing electrical remodeling caused by several days of atrial tachycardia.

Accuracy and limitations of published algorithms using the twelve-lead electrocardiogram to localize overt atrioventricular accessory pathways.

INTRODUCTION: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12-lead ECG to localize AV accessory pathways (APs). METHODS AND RESULTS: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6% +/- 10.9% vs 61.2% +/- 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6% +/- 11.2% vs 52.3% +/- 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%). CONCLUSION: Our study suggests that the accuracy of algorithms relying on the 12-lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.

Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation.

BACKGROUND: We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current (ICa) and that this is the principal mechanism of the action potential duration and refractoriness changes that characterize tachycardia-induced atrial remodeling. The present study was designed to determine whether atrial tachycardia alters biochemical indices of the number of L-type Ca2+ channels and/or of the number and binding affinity of beta-adrenergic receptors. METHODS: In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridine receptors were determined with the use of 3H-nitrendipine and that of beta-adrenergic receptors with 125I-iodocyanopindolol. Results were obtained with preparations from dogs paced at 400/min for 1 (P1, n = 20), 7 (P7, n = 9), and 42 (P42, n = 9) days, and compared with observations in sham-operated controls (P0, n = 14). RESULTS: Pacing reduced the Bmax of dihydropyridine receptors, from 157 +/- 18 fmol/mg (P0) to 116 +/- 9 fmol/mg (P1, P < 0.05), 100 +/- 14 fmol/mg (P7, P < 0.05) and 94 +/- 9 fmol/mg (P42, P < 0.01). The affinity of dihydropyridine receptors was unchanged, with the Kd averaging 711 +/- 102 pM. 656 +/- 74 pM, 633 +/- 155 pM and 585 +/- 92 pM in P0, P1, P7 and P42 dogs. Neither Bmax nor Kd of beta-adrenergic receptors was altered by rapid pacing. Values of Bmax of dihydropyridine receptors correlated with atrial ICa current density (r2 = 0.95) and ERP (r2 = 0.99). CONCLUSIONS: Rapid atrial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of beta-adrenergic receptors. The reductions in ICa that play an important role in the atrial electrical remodeling by which 'AF begets AF' appear to be due at least in part to a decrease in the number of L-type Ca2+ channels in cardiac cell membranes.

Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.

BACKGROUND: Studies of atrial fibrillation (AF) due to atrial tachycardia have provided insights into the remodeling mechanisms by which "AF begets AF" but have not elucidated the substrate that initially supports AF before remodeling occurs. We studied the effects of congestive heart failure (CHF), an entity strongly associated with clinical AF, on atrial electrophysiology in the dog and compared the results with those in dogs subjected to rapid atrial pacing (RAP; 400 bpm) with a controlled ventricular rate (AV block plus ventricular pacemaker at 80 bpm). METHODS AND RESULTS: CHF induced by 5 weeks of rapid ventricular pacing (220 to 240 bpm) increased the duration of AF induced by burst pacing (from 8+/-4 seconds in control dogs to 535+/-82 seconds; P<0.01), similar to the effect of 1 week of RAP (713+/-300 seconds). In contrast to RAP, CHF did not alter atrial refractory period, refractoriness heterogeneity, or conduction velocity at a cycle length of 360 ms; however, CHF dogs had a substantial increase in the heterogeneity of conduction during atrial pacing (heterogeneity index in CHF dogs, 2. 76+/-0.16 versus 1.46+/-0.10 for control and 1.51+/-0.06 for RAP dogs; P<0.01) owing to discrete regions of slow conduction. Histological examination revealed extensive interstitial fibrosis (connective tissue occupying 12.8+/-1.9% of the cross-sectional area) in CHF dogs compared with control (0.8+/-0.3%) and RAP (0. 9+/-0.2%) dogs. CONCLUSIONS: Experimental CHF strongly promotes the induction of sustained AF by causing interstitial fibrosis that interferes with local conduction. The substrates of AF in CHF are very different from those of atrial tachycardia-related AF, with important potential implications for understanding, treating, and preventing AF related to CHF.

Importance of refractoriness heterogeneity in the enhanced vulnerability to atrial fibrillation induction caused by tachycardia-induced atrial electrical remodeling.

BACKGROUND: Rapid atrial activation causes electrical remodeling that promotes the occurrence and the maintenance of atrial fibrillation (AF). Although remodeling has been shown to alter electrophysiological variables, the spatial uniformity of these changes is unknown. METHODS AND RESULTS: Dogs subjected to rapid atrial pacing (400 bpm) for 24 hours (n=12) were compared with sham-operated dogs (instrumented but not paced, n=12). Epicardial mapping (240 bipolar electrodes) and extrastimulation at a large number of sites (mean+/-SEM, 66+/-4 per dog) were used to evaluate atrial activation and the heterogeneity of the effective refractory period (ERP), respectively. Rapid pacing increased both the percentage of sites at which AF could be induced by single premature stimuli (from 2.6+/-0.9% to 11.8+/-2.8%, P=0.007) and AF duration (from 39+/-28 to 146+/-49 seconds, P=0.03). Atrial tachycardia decreased atrial ERP (from 120+/-4 to 103+/-2 ms, P=0.003), increased the coefficient of variation of ERP (from 14.9+/-0.9% to 20.7+/-0.9%, P<0.0001), and accelerated conduction velocity (from 91+/-2 to 108+/-3 cm/s, P=0.0004), with no change in the wavelength. The increase in ERP heterogeneity was due both to interregional differences in the extent of ERP remodeling and to increased intersite variability within regions. Stepwise multilinear regression indicated that ERP heterogeneity was an independent determinant of the inducibility (P<0.0001) and duration (P<0.0001) of AF, whereas ERP per se and wavelength were not significant determinants. Combined mapping of AF induction and atrial ERP showed that premature extrastimuli induced AF at sites with short ERP by causing local conduction slowing and/or block in adjacent zones with longer ERP values. CONCLUSIONS: Atrial tachycardia causes nonuniform remodeling of atrial refractoriness that plays an important role in increasing atrial vulnerability to AF induction and the duration of induced AF.

[Large coronary artery aneurysms. A study of 20 clinical cases in the elderly]. / Anévrismes volumineux des artères coronaires. Etude de 20 observations anatomo-cliniques chez l'adulte âgé.

The aim of this study was describe the anatomical features of coronary aneurysms and assess their role in causing death. Twenty clinico-pathological cases were recensed prospectively out of 8,920 autopsies (0.22%). The average age at death was 68 +/- 20 years (14 men and 6 women). Death was due to a cardiac cause in 90% of cases. The aneurysms were located on a single coronary artery in 14 cases, on 2 coronary arteries in 3 cases, and on all three arteries in 3 cases with a mean maximum diameter of 15 +/- 4.5 mm. Aneurysms of the right coronary artery were the most common (p < 0.01) and the largest (16.7 +/- 3.8 mm; p = 0.12) and circumflex arteries (12 +/- 3.1 mm, p = 0.03). The diameter of the coronary aneurysm was greater in the more elderly patients (r = 0.51 ; p = 0.022). The coronary aneurysms were diffuse in 10 subjects and localised in the other 10 (mainly fusiform and proximal). Only 3 aneurysms were directly associated with significant stenosis of the same artery. The aetiology was atherosclerosis in 18 cases, with associated extra-cardiac disease in 14 cases; the other 2 cases were dystrophic. The underlying anatomical abnormality constantly found was variable degrees of atrophy and destruction of the musculo-elastic elements of the media, a source of dilation. In 80% of cases, thrombosis of the aneurysm was directly or indirectly responsible for death. Coronary artery aneurysms are a rare finding and are frequently complicated by fatal thrombosis. Coronary angiographic detection of this condition characterised by the large size and absence of stenosis of the artery should lead to prophylactic antithrombotic therapy.

[Post-radiotherapy pericarditis; a clinical and pathological study of 75 cases]. / Péricardites post-radiothérapiques; étude clinique, évolutive et histopathologique de 75 cas.

The outcome of 75 cases of post-radiotherapy pericarditis severe enough to lead to surgery, was reviewed from 1970 to September 1995. Four clinical forms were identified: acute pericarditis resistant to medical treatment (12 cases), large chronic pericardial effusions resistant to medical treatment (16 cases), chronic, compressive effusions (35 cases) and signs of pericardial constriction (12 cases). The medical conditions irradiated were Hodgkin's disease (41 cases), followed by carcinomas (27 cases), malignant lymphomas, thymoma and seminoma. Forty-three deaths were observed during the study period (only 4 unrelated to the neoplasia or radiotherapy) after a mean interval of 7.4 years after radiotherapy and 2.5 years after surgical biopsy: 25 were related to cardiopulmonary complications of radiotherapy: 14 were due to recurrence of the malignant disease or the appearance of another tumour. Fifty-two pericardial effusion drainage procedures and 28 pericardectomies were performed, due to the necessity for reoperation. The authors have tried to determine therapeutic indications based on recognised physiopathological data and the anatomical aspects of the four different clinical forms. The prognosis is affected by post-radiotherapy fibrosis which extends beyond the pericardium to involve other cardiac structures and the pulmonary parenchyma. However, it must be emphasised that the initial survival of all these patients was due to the radiotherapy.

[Apparently idiopathic chronic pericardial effusion. Long-term outcome in 71 cases]. / Epanchements péricardiques chroniques d'apparence idiopathique. Evolution à long terme de 71 cas.

Seventy one cases of apparently idiopathic chronic pericardial effusion were systematicaly followed up. There were 3 inclusion criteria: patients had to be symptomatic with radiological cardiomegaly without tamponade or an acute onset; the effusion had to be stable for more than 3 months despite medical therapy at the time of surgery; the parietal pericardium removed at surgery had to be of normal histopathological appearances. Cases with a discernable classical cause of pericardial effusion were excluded: previous mediastinal radiotherapy, connective tissue diseases, malignancies, chronic infection or a recent episode of acute pericarditis. There were 9 deaths during the first five postoperative years, one of which was related to the pericardial disease and surgery. By definition, no cause was found but in one third of cases a relationship between the pericarditis and other disease processes was possible. The management of these large pericardial effusions resistant to treatment without any apparent underlying pathology and in which echocardiography only shows a large effusion should be surgical with drainage of the pericardial cavity, allowing exclusion of aetiologies which are non-identifiable by other methods, with a negligeable operative risk even in elderly patients and good long-term clinical results. This recommendation is based on systematic follow-up of over 5 years in 57 of our 71 cases; after drainage, only one of the nine deaths observed was related to the pericardial disease itself and 59, subjects (83%) had no further symptomatic pericardial disease.

Heterogeneous effect of quinidine on the ventricular depolarization process assessed by the spatial velocity electrocardiogram of the QRS complex. Preliminary report of a new investigative method.

The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.

Interactive and dynamic ECG analysis. Is it just an IDEA or a clinically relevant approach?

The idea that it is possible to increase the overall electrocardiographic (ECG) diagnostic performance is developed in this paper, provided that different programs or methods and various data sources are combined and that the dynamicity of the patients' record is considered. This dynamicity consists of the following three dimensions: beat-to-beat changes within continuous recordings, changes between serial records, and clinical events. Data integration should be time- or event-related, and multisources data should interact. Interactive and dynamic ECG analysis (IDEA), however, can only be achieved if powerful clinical workstations are developed that access the right information, when and where needed, a challenge that the IDEA workstation intends to accomplish.

Stratification of time-frequency abnormalities in the signal-averaged high-resolution ECG in postinfarction patients with and without ventricular tachycardia and congenital long QT syndrome.

Having developed sound mathematical techniques that allow precise mapping of cardiac signals in the time-frequency (TF) and time-scale planes, the next important issue is to extract from these representations information that best reflects the electrophysiologic and anatomic derangement unique to patients at risk of arrhythmias and other cardiac diseases. In this study, the authors present a new method that stratifies the magnitude of the TF transforms of abnormal cardiac signals into distinguishing features by comparing the means of the coefficients of the TF transforms of any study population to the corresponding means of a control population using a standard ANOVA technique. This results in a three-dimensional mapping of the high-resolution ECG into time, frequency, and P value components. Significant energy increases are given positive P values and depressed energies are given negative P values: these are ranked according to a color scale. The method was tested on two study populations: postmyocardial infarction patients with documented ventricular tachycardia (MI+VT, n = 23) and without (MI-VT, n = 40) and patients with congenital long QT syndrome (LQTS, n = 19). Two groups of healthy control subjects (n = 31 and n = 40) were used as a reference group matched for sex. The study results were based on the Morlet analyzing wavelets, with frequencies ranging from 40 to 250 Hz in 10 logarithmically progressing scales, and computed millisecond per millisecond over a 350-ms analyzing time window, starting from 100 ms before the onset of the QRS. The patients with MI+VT displayed significantly increased high-frequency components in the 40-250-Hz frequency range, corresponding to prolonged QRS duration and late potentials in the area from 80 to 150 ms after QRS onset. Significantly depressed energy (P < 10(-4)) was also observed for the 40-106-Hz frequency range in the first 50 ms of the QRS complex, mainly in lead Y and in the magnitude vector. In patients with LQTS, significant modifications (P < 10(-2)) were observed in the first half of the QRS and in the ST-segment, in all leads, revealing anomalies in the genesis of the ventricular depolarization and repolarization processes. In conclusion, the authors propose a new method for the stratification of abnormal TF components occurring in the signal-averaged high-resolution electrocardiogram of patients at risk of VT and fibrillation under different pathologic conditions.

[Diagnostic value of exercise test in the evaluation of sustained ventricular arrhythmia]. / Intérêt diagnostique de l'épreuve d'effort dans l'évaluation des arythmies ventriculaires soutenues.

The authors undertook a prospective study comparing exercise testing and programmed ventricular stimulation in order to assess the diagnostic value and risks of exercise stress testing in patients with sustained ventricular arrhythmias. Fifty-five consecutive patients (47 men and 8 women) with an average age of 47 +/- 15 years were included. The initial condition requiring investigation was sustained ventricular tachycardia (47 cases) and ventricular fibrillation (8 cases). The patients had ischaemic heart disease (N = 18), dilated cardiomyopathy (N = 9), valvular heart disease (N = 4) and congenital heart disease (N = 3). Six patients presented with arrhythmogenic right ventricular dysplasia and 15 patients had apparently normal hearts. Four episodes of sustained ventricular tachycardia (7.3%) and 10 non-sustained ventricular tachycardia (18.2%) were induced by exercise testing. One poorly tolerated episode of ventricular tachycardia required cardioversion. No signs of myocardial ischaemia were observed in association with the induced ventricular tachycardia Patients with ventricular tachycardia induced by exercise were significantly younger (39.5 +/- 12.5 vs 49.5 +/- 15.4 years; p = 0.04) and attained a lower predicted maximal heart rate (82.2 +/- 14.6 vs 91.4 +/- 14.4%; p = 0.04), but the underlying pathologies were the same, as were the initial arrhythmias and the level of exercise attained. With respect to the clinical circumstances of induction of the initial ventricular arrhythmia, patients with ventricular tachycardia induced by exercise had an increased tendency to arrhythmias during effort or stress (7/14 vs 8/41; p = 0.06). Programmed ventricular stimulation induced more ventricular tachycardias than exercise testing (36/55 vs 14/55; p < 0.0001). The results of exercise testing were not correlated to those of programmed stimulation (p = 0.38).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. A meta-analysis.

We examined the influence of phosphodiesterase inhibitors (PDIs) on mortality in patients with overt chronic heart failure. A total of 13 randomised, placebo-controlled trials of PDIs involving 2808 patients were selected. Meta-analysis, using data for all patients, showed that there was a non-significant (P = 0.16) increase of about 17% in the mortality rate of patients receiving a PDI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.94-1.46]. However, the observed treatment effects were found to be heterogeneous due to the results from the trials on vesnarinone. The heterogeneity became non-significant (P = 0.77) when these trials were removed, and a significant increase in the mortality rate was observed under treatment with the other PDIs (OR 1.41, 95% CI 1.11-1.79). In the subgroups of patients with or without additional vasodilator (VD) treatment, similar results were observed (PDI with VD: OR 1.3, 95% CI 1.03-1.7; PDI without VD: OR 2.04, 95% CI 1.1-3.8). These results indicate that PDIs (with the exception of vesnarinone) should not be prescribed for long-term use in patients with overt chronic heart failure. Additional vasodilator treatment in patients receiving PDIs for chronic heart failure does not explain the increased mortality seen with PDIs. This toxicity must, therefore, arise by other mechanisms. Further experimental and clinical evaluation is needed to confirm the beneficial influence of vesnarinone on survival in chronic heart failure patients and to identify the mechanism(s) differentiating this agent's therapeutic effect from that of other PDIs.

The role of an initial single-blind placebo period in phase I clinical trials.

The effect of an initial single-blind placebo period in a phase I clinical trial was assessed in 12 volunteers who underwent five weekly treatment periods, consisting of treatment on the first day and a six-day wash-out period. An initial single-blind placebo period was followed by three different single doses of a platelet-aggregation factor inhibitor and another placebo period, under a double-blind Latin square design. Reports of abnormal symptoms were collected using a questionnaire designed by our group. A total of 13 abnormal symptoms were reported during the first period and only nine for the following four periods, indicating a clear placebo period effect. These preliminary results suggest that an initial single-blind period may be usefully included in phase I clinical trials.