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Biomedical subjects

P Coumel

Publications and source records attributed to P Coumel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA study. The College of French Cardiologists.

BACKGROUND: The clinical presentation and causes of atrial fibrillation (AF) in the 1990s may differ from AF seen 2 to 3 decades ago. It was the objective of this prospective study to characterize various clinical presentations and underlying conditions of patients with AF observed in general practice in France. METHODS AND RESULTS: The study population comprised 756 patients (19 to 95 years of age) with electrocardiographically documented AF subdivided into paroxysmal (<7 days), chronic (last episode >1 month) and recent onset AF(persistent >7 days and<1 month). Symptoms were present in 670 patients (88.6%). The relative prevalences of paroxysmal, chronic, and recent onset AF were 22.1%, 51.4%, and 26.4%, respectively. Cardiac disorders, present in 534 patients (70.6%), included hypertension (39.4%), coronary artery disease (16.6%), and myocardial diseases (15.3%) as the most common. Rheumatic valvular disease represented a common cause in women (25. 0%) but not in men (8.0%). The paroxysmal group differed by a high percentage of palpitations (79.0%) and a low percentage of underlying heart disease (53.9%). With a mean follow-up of 8.6+/-3.7 months, 28 patients (3.7%) died, including 6 fatal cerebrovascular accidents. Among the 728 patients who survived, congestive heart failure occurred in 30 patients (4.1%), and embolic complications occurred in 13 patients (1.8%). In the paroxysmal AF group, 13 patients (8.0%) developed chronic AF and 51 (31.3%) had AF recurrences. At the time of follow-up, 53 patients (14.3%) from the chronic AF group and 108 patients (55.7%) from the recent onset AF group were in sinus rhythm. CONCLUSIONS: This large-scale study establishes the current demographic profile of out-of-hospital patients with AF and highlights some of the changes that have occurred in the past decades, including a particular shift in cardiac causes toward nonrheumatic AF. This study also demonstrates significant differences between various subsets of AF.

Adult↗
PubMed1999

C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence.

BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in which 4 genes encoding ion-channel subunits have been identified. Most of the mutations have been determined in the transmembrane domains of the cardiac potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3' part of HERG for mutations. METHODS AND RESULTS: New specific primers allowed the amplification of the 3' part of HERG, the identification of 2 missense mutations, S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp insertion, 3108+1G. Hypokalemia was a triggering factor for torsade de pointes in 2 of the probands of these families. Lastly, in a large family, a maternally inherited G to A transition was found in the splicing donor consensus site of HERG, 2592+1G-A, and a paternally inherited mutation, A341E, was identified in KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The discovery of mutations in the C-terminal part of HERG emphasizes that this region plays a significant role in cardiac repolarization. Clinical data suggests that these mutations may be less malignant than mutations occurring in the pore region, but they can become clinically significant in cases of hypokalemia. The first description of 2 patients with double heterozygosity associated with a dramatic malignant phenotype implies that genetic analysis of severely affected young patients should include an investigation for >1 mutation in the LQT genes.

Adolescent↗
PubMed1999

Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.

Base Sequence↗
PubMed1999

QT interval and arrhythmic risk assessment after myocardial infarction.

To assess ventricular repolarization features as predictors of ventricular tachyarrhythmias (VT) in patients with previous myocardial infarction, we performed a dynamic study of QT interval from 24-hour electrocardiographic data. QT rate dependence was enhanced in patients with VT when compared with patients without VT.

Electrocardiography↗
PubMed1999

QT interval analysis on ambulatory electrocardiogram recordings: a selective beat averaging approach.

A computerised method for the analysis of QT intervals in ambulatory ECG recordings is presented. This approach is based on selective beat averaging which allows one to process P-QRS-T complexes together with the environment that characterises them. Long-term autonomic nervous system influences are accounted for by separating the analysis over different circadian periods. Effects of QT recovery time are taken into account by requiring a stable heart rate preceding each beat to be averaged. Before averaging, beats are resampled and realigned with respect to the R-wave peak estimated by parabolic interpolation. Averaged ECG templates are then analysed with an algorithm which automatically detects QRS complex and T-wave features. Repolarisation analysis is based on first and second derivatives of lowpass filtered ECG (recursive Butterworth filter). The QT/RR relationship and the circadian QT variation at identical heart rate were analysed in 14 normal individuals. When performed at stable heart rate conditions and when confined to well-defined circadian periods, the QT/RR relationship was strongly linear (r = 0.95 +/- 0.06); in addition, the slope of this relation changed between day and night (respectively, 0.197 +/- 0.07 and 0.139 +/- 0.03, p < 0.01). The range of circadian QT variation at identical heart rate was approximately 20 ms for both males and females.

Algorithms↗
PubMed1999

Circadian modulation of QT rate dependence in healthy volunteers: gender and age differences.

QT rate dependence is known to be linked with both circadian variations of the autonomic tone and gender. However, age and heart rate variability (HRV) influences are not well established. The QT/RR relationship was evaluated, separately during the day and at night, on 24-hour electrocardiogram in 60 healthy subjects (30 men) divided into three homogeneous groups (group 1, 20-29; group 2 30-39; group 3, 40-50 years). QT rate dependence was larger during the day in both genders. Women showed stronger QT rate dependence (0.195 during the day vs. 0.154 in men P< .0001). The circadian modulation decreased with increasing age (day/night slope differences: group 1, 0.038; group 2, 0.031; group 3, 0.001; analysis of variance P<.05). In addition, QT rate dependence increased as mean RR decreased (r = -0.58, P<.0001) and decreased as HRV parameters increased. Multiple influences on QT rate dependence can be found: not only circadian and gender modulation, but also age, heart rate, and HRV interventions.

Adult↗
PubMed1999

[Mechanism of spontaneous occurrence of tachycardia].

Tachycardias arise from an arrhythmogenic substrate and a trigger factor, an extrasystole, the two factors being under the influence of the autonomic nervous system. The study of the mechanisms of spontaneous initiation of arrhythmias must, therefore, take these three factors and their interactions into account. The frequency dependency of an arrhythmia and the sensitivity of the substrate to the adrenergic system varies with time in a given subject and from one patient to another according to the presence and type of cardiac disease. The mode of initiation of most ventricular tachycardias and the therapeutic consequences may be understood: in some forms of cardiac disease, such as arrhythmogenic right ventricular dysplasia, the increase in heart rate which usually precedes sustained ventricular arrhythmias is only perceptible in mild or recent forms, unlike the more chronic dysplasias. This suggests that the arrhythmogenic substrate becomes more sensitive to catecholamines with time, and therefore requires smaller changes in sympathetic tone in order to be expressed (adrenergic paradox). Heart rate changes accompany modifications of sinus variability. Holter monitoring has shown, and this has been confirmed by recordings obtained from patients with implanted automatic defibrillators, that global sinus variability decreases before the initiation of a ventricular arrhythmia. Studies of the dynamics of ventricular repolarisation should also confirm the changes of QT frequency-dependency. The analysis of the initiation of arrhythmias would only have an academic interest if this was limited to a purely descriptive exercise. It is one of the best means of understanding arrhythmias and their therapeutic implications. The development of computerised methods of analysis of Holter monitoring should lead to further progress in this field.

Cardiomegaly↗
PubMed1999

[Congenital long QT syndrome. The value of genetics in prognostic evaluation].

The congenital long QT syndrome (QTL) is a heterogenic clinical and genetic entity characterised by prolongation of the QT interval which may be complicated by syncope and sudden death. Four genes have been identified for the cardiac potassium (KCNQ1, HERG and KCNE1) and sodium (SCN5A). The aim of this study was to assess the prognosis of the disease by the site of mutation identified on the morbid gene. Thirty-two genotyped families participated to this study. Each subject gave a clinical history, an ECG and a search for genetic mutation. Eighteen mutations in the transmembrane domains of KCNQ1 were identified in 25 families and 2 mutations in the C-terminal part were found in 4 families. The phenotype was less severe in C-terminal part mutations: less syncopes and sudden deaths (22 vs 55%, p < 0.001) and a shorter QTc (458 +/- 31 ms vs 479 +/- 31 ms, p = 0.0003). Three mutations were detected in the C-terminal part of HERG in 3 different families. Their phenotype was less severe with syncoped related to hypokalemia. The authors also report the case of a family in which two subjects who were the most severely affected had two mutations, one in HERG and the other in KCNQ1. This study confirms the value of a genetic research in assessing the severity of the congenital long QT syndrome.

Adolescent↗
PubMed1998

[Congenital long QT syndrome].

SEVERAL FORMS: Congenital long QT syndrome is a clinically (with and without deafness) and genetically (recessive or dominant autosomal inheritance) heterogeneous entity characterized by a long QT interval on the ECG associated with the risk of severe ventricular arrhythmia (torsade de pointes, ventricular fibrillation) and subsequent syncope or sudden death. GENETIC DATA: This rare familial syndrome is transmitted by different modes of inheritance and occurs in subjects with a morphologically normal heart. The severity of the prognosis justifies screening tests. The genetic origin of the disease has been confirmed and at least 5 loci and 4 genes have been identified, giving a perfect illustration of adrenergic ventricular rhythm disorders. Beta-blockers are used as first line treatment in symptomatic patients. PREVENTION: All drugs favoring QT interval lengthening are contraindicated in all subjects with a genetic anomaly. All members of the direct family must have a Holter recording and genotype in order to identify mutation carriers or asymptomatic patients.

Adrenergic beta-Antagonists↗
PubMed1998

Dynamic analysis of dofetilide-induced changes in ventricular repolarization.

OBJECTIVE: To use dynamic electrocardiographic (ECG) techniques to study the influence of heart rate on dofetilide-induced QT prolongation among healthy volunteers. BACKGROUND: The extent to which heart rate modulates QT prolongation induced by the new class III antiarrhythmic drug dofetilide is a matter of debate. METHODS: Ten healthy volunteers underwent two 24-hour ECG recordings, one in the absence of dofetilide and the other after a single oral dose of 0.5 mg dofetilide. Two 4-hour periods were defined during the second recording: Dh, which corresponded to stable high concentration of the drug, and D1, which corresponded to low concentration of the drug. Corresponding baseline recording periods, Ch and C1, matched by time with Dh and D1 were selected from the control ECG recording in the absence of dofetilide. QT versus R-R relations were compared in the presence and absence of dofetilide. The QT versus R-R relation slope was used as an index of the rate dependence QT prolongation. Rate-independent changes in QT duration were also analyzed. RESULTS: During Dh, dofetilide induced a mean 12% lengthening of ventricular repolarization. Dynamic ECG analysis showed that this prolongation increased as R-R cycles became longer, a phenomenon known as reverse rate dependence. However, QT prolongation persisted at the shortest (600 ms) R-R cycle length that could be analyzed. During D1, dynamic ECG analysis showed a persistent, although small, effect of dofetilide on both QT prolongation (3%) and reverse rate dependence of this effect. CONCLUSIONS: Dofetilide prolongs QT duration, and this class III effect is influenced by heart rate. Although dofetilide-induced QT prolongation decreases when the R-R cycle shortens, this reverse rate dependence is only partial because marked QT prolongation persists at an R-R cycle of 600 ms. The results of our study indicated that dynamic ECG techniques can be useful in detection of subtle, drug-induced changes in the duration of ventricular repolarization.

Administration, Oral↗
PubMed1998

Diagnostic performance of QT interval variables from 24-h electrocardiography in the long QT syndrome.

AIMS: The long QT syndrome is mainly defined by QT interval prolongation (QTc > 0.44s). However, data obtained in genotyped patients showed that resting QTc measurement alone may be inaccurate for ascertaining the phenotype. The aim of this study was to evaluate the diagnostic performance of QT interval rate-dependence in untreated chromosome 11-linked patients. METHODS: The study population consisted of 25 untreated long QT patients linked to chromosome 11 and 25 age- and gender-matched controls. QTc intervals were measured on 12-lead resting ECG recordings. From 24-h Holter recordings, the slope of the relationship between ventricular repolarization and heart rate was studied separately day and night to assess neural modulation. Mean heart rates and rate-dependences of QT and Q-maximum of T (QTm) intervals were compared between long QT patients and controls for both time periods. RESULTS: In both groups, the rate-dependences were modulated by day-night influences. When compared to controls, long QT patients showed a significant increase at night in QT/RR slopes (0.158 +/- 0.05 vs 0.117 +/- 0.03, P = 0.002) and QTm/RR slopes (0.163 +/- 0.05 vs 0.116 +/- 0.04, P = 0.0006). Multivariate analysis, adjusting QTc interval on age and gender, discriminated between long QT patients and controls with a 76% sensitivity and a 84% specificity. A 96% sensitivity and a 96% specificity were reached by taking into account the QTm/RR slope at night, the QTc interval and the mean heart rate during the day. CONCLUSION: QT interval variables obtained from 24-h ECG recordings improve long QT syndrome diagnosis by showing an increased nocturnal ventricular repolarization rate-dependence in genotyped chromosome 11-linked patients.

Adolescent↗
PubMed1998

Heart rate variability in passive tilt test: comparative evaluation of autoregressive and FFT spectral analyses.

The dynamic response of the autonomic nervous system during tilting is assessed by changes in the low (LF) and high frequency (HF) components of the RR series power spectral density (PSD). Although results of many studies are consistent, some doubts related to different methodologies remain. Specifically, the respective relevance of autoregressive (AR) and fast Fourier transform (FFT) methods is often questioned. Beat-to-beat RR series were recorded during 90 degrees passive tilt in 18 healthy subjects (29 +/- 5 years, eight females). FFT-based (50% overlap, Hanning window) and AR-based (Levinson-Durbin algorithm) PSDs were calculated on the same RR intervals. Powers in very low frequency (VLF: < 0.04 Hz), LF (0.04-0.15 Hz), and HF (0.15-0.40 Hz) bands were calculated either by spectrum integration (FFT and ARIN), by considering the highest AR component in each band (ARHP), or by summation of all AR components (ARAP). LF and HF raw powers (ms2) were normalized by total power (%P) and by total power after removal of the VLF component (nu). AR and FFT total powers were not different, regardless of body position. In supine condition, when compared to ARHP and ARAP, FFT underestimated VLF and overestimated LF, whereas in tilt position FFT overestimated HF and underestimated LF. However, supine/tilt trends were consistent in all methods showing a clear reduction of HF and a less marked increase of LF. Both normalization procedures provided a significant LF increase and further magnified the HF decrease. Results obtained with ARIN were remarkably close to those obtained with FFT. In conclusion, significant differences between AR and FFT spectral analyses do exist, particularly in supine position. Nevertheless, dynamic trends provided by the two approaches are consistent. Normalization is necessary to evidence the LF increase during tilt.

Adult↗
PubMed1998

[QT interval and drugs. Recommendation for drug prescription for patients with long QT syndrome. Clinical Research Group of INSERM 4940 12: Diagnostic Clinic of Congenital Long QT Syndrome].

The genetics of the long QT syndrome are now better understood. However, there is much heterogeneity as three different genes have already been identified affecting the function of sodium and potassium channels. The aim of these recommendations is to draw up a list of drugs which are contraindicated or not recommended in patients with congenital long QT syndromes. The conraindicated drugs are those with which torsades de pointe have already been described. Drugs not recommended are substances which are not electrohysiologically neutral and for which, in view of their modes of action, their metabolism or belonging to a particular therapeutic class, make them very difficult to use in those patients. It is therefore better not to prescribe them whenever possible in this condition. These substances belong mainly to cardiovascular (especially antiarrhythmic), psychotropic, anti-infectious and antiallergic groups of drugs.

Anti-Allergic Agents↗
PubMed1998

[Implantable automatic defibrillators in the treatment of ventricular tachycardia].

The implantable automatic defibrillator (IAD) is the treatment of choice of malignant ventricular arrhythmias or those resistant to pharmacological or ablative techniques. However, the small number of implantations in France, the presence of many different models, the cost and sophistication of the latest models explain why IAD remain a poorly known therapeutic method because it is highly specialised and reserved for cardiological departments with a rhythmological interest. Several factors suggest that the number of implantations will increase in the future. Firstly, the techniques of implantation have been considerably simplified and associated with technological improvements of the devices, and, secondly, publication of several trials (MADIT, AVID), even if the conclusions in favour of IAD must be carefully interpreted, will change our methods of management of patients with severe ventricular arrhythmias. The current indications of IAD in ventricular tachycardia and future prospects are discussed in the light of new data.

Defibrillators, Implantable↗
PubMed1997

Instant power spectrum analysis of heart rate variability during orthostatic tilt using a time-/frequency-domain method.

BACKGROUND: Spectral analysis of heart rate (HR) variability (HRV) requires, as a rule, some level of stationarity and, as a result, is inadequate to quantify biological transients. A time-/frequency-domain method (TF) was developed to obtain an instant spectral power (SP) of HRV during tilt. METHODS AND RESULTS: HR was recorded by Holter monitoring in volunteers and analyzed with a TF, the smoothed pseudo-Wigner-Ville transformation (SPWVT), with the table inclination randomly set or continuously increased while the table rotated in head-up position. (1) The SPWVT assesses, beat by beat, the instant center frequency (ICF) of the SP. ICF correlates better with instant HR than the ratio of low- (LF) to high-frequency (HF) oscillations. The transient effect of tilt is better characterized as a shift of SP toward lower frequencies than by changes in amplitudes. (2) The method evidences variations of HR from one second to another. During the passage to head-up position, the vagal withdrawal and the sympathetic activation occur nearly simultaneously, as indicated by the instant changes in both LF and HF amplitudes and ICF. (3) The averaged results of the SPWVT give results similar to those previously obtained with autoregressive algorithms. CONCLUSIONS: The SPWVT is a new tool to explore HR transitions such as periods before episodes of arrhythmias on a time scale of one beat and allows quantification of an instant frequency index (ICF) that closely reflects the instantaneous relationship between sympathetic and vagal modulations.

Adult↗