High prevalence of ventricular repolarization abnormalities in people carrying TGFßR2 mutations.

Mutations in the TGFßR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFßR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFßR2 mutations. ECG findings from 58 mutation carriers patients (TGFßR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFßR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFßR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.

Influence of blood glucose on heart rate and cardiac autonomic function. The DESIR study.

OBJECTIVES: To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability. METHODS: Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability. RESULTS: Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r=-0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration. CONCLUSIONS: Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability.

[Primary anomalies of ventricular repolarisation]. / Anomalies primaires de la repolarisation ventriculaire. Conséquences electrophysiologiques.

The duration of repolarisation is the main determinant of the refractory period and therefore plays a major electrophysiological role. Ventricular repolarisation can be influenced or modified by very many extrinsic factors responsible for so-called secondary changes or anomalies. On the contrary, primary anomalies of ventricular repolarisation correspond to intrinsic anomalies of ionic conduction which in turn affect repolarisation. Primary anomalies of ventricular repolarisation are the consequences of vascular disease, which is the origin of both electrocardiographic anomalies and rhythm disorders, and which can result in sudden death from ventricular fibrillation. Three clinical syndromes correspond with these definitions: long QT syndrome, short QT syndrome, and Brugada syndrome. Much of the experimental work seems to show that arrhythmogenic action results mostly from an increase in the heterogeneity of the refractory periods, whether this involves a prolonged, short or even normal repolarisation time. The various experimental models also give a better understanding of the repolarisation changes observed on the electrocardiogram. Knowledge of the mechanisms responsible for arrhythmias due to primary anomalies of ventricular repolarisation could provide a model for secondary anomalies.

[Recent concepts of the Brugada syndrome, the long QT syndrome and adrenergic ventricular tachycardias]. / Aspects récents dans le syndrome de Brugada, le syndrome du QT long et les TV catécholergiques.

The clinical syndromes responsible for sudden death have benefited from spectacular advances in recent years. The authors propose a brief review of the genetic, electrophysiological, physiopathological and clinical characteristics of the long QT syndrome, Brugada's syndrome, adrenergic ventricular tachycardias and the short QT syndrome. The initial concept of one gene responsible for one pathology has uncovered new zones of complexity within diseases considered to be monogenetic in origin. These new findings have impacted on diagnostic and therapeutic strategies of these conditions. However, the assessment of the arrhythmic risk and the choice of treatment in individual cases still remain almost exclusively the domain of clinical judgement. Similarly, the better understanding of the mechanisms of the arrhythmias in these syndromes has opened up new specific therapeutic approaches which require validation by clinical trial.

[Role of antiarrhythmics in the treatment of paroxysmal atrial fibrillation]. / Place des antiarythmiques dans le traitement de la fibrillation auriculaire paroxystique.

Atrial fibrillation is not a homogenous entity. Numerous parameters affect its cause, its continuation, and the arrest of an attack. The presence or absence of cardiopathy and left ventricular dysfunction play a major role via the electrophysiological and haemodynamic consequences and the repercussions on the state of the autonomic nervous system, and finally on the effect of anti-arrhythmics themselves. This shows the importance of taking into account all of these parameters together in order to adapt the therapeutic approach. Equally, this underlines the difficulty in interpreting clinical studies comparing pharmacological treatments when the populations treated are poorly defined or very heterogenous. Most often, one drug is not more or less effective than another, it is more or less suited to the patients treated. The frequency of recurrences of AF despite anti-arrhythmic treatment (on average 50% to 60% at one year) means that in paroxysmal AF the goal of anti-arrhythmic treatment is relatively modest: essentially reducing the frequency, duration and severity of AF attacks, allowing an improvement in the quality of life. The consequences in daily practice are clear: one must ensure good patient compliance and minimise the risks of treatment: side effects of and pro-arrhythmic effects of anti-arrhythmics.

A neural network approach for predicting and modelling the dynamical behaviour of cardiac ventricular repolarisation.

Physiological signals are usually patient specific, and they are difficult to predict, especially for the cardiovascular system. New methods capable to be adapted to each case and to learn the singular behavior of heart functions should be developed to support physicians in their decision-making. One of the most widely studied relations is the QT-RR one, between the total duration of the ventricle activation and inactivation, and the heart rate. In the past, different studies were made to approach this relation in the steady state. In this paper, a new method for modeling and predicting the transient dynamic behaviour of QT interval in relation to changing RR intervals is presented using artificial neural networks.

Influence of atenolol on the kinetics of RT interval rate adaptation in conscious dogs.

The objective was to test an effect of atenolol independent of heart rate on electrocardiographic RT rate adaptation by investigating RT adaptation during spontaneous rate and after an abrupt change of atrial rate (study of RT delay). Digital electrocardiograms were recorded from eight conscious dogs. Analysis of RT interval (measured from QRS apex to end of T) was performed on a beat-to-beat basis. The protocol was repeated in the control state and after atenolol administration (2 mg/kg). Regarding spontaneous heart rate, an increased or decreased RR duration did not modify the beat-to-beat relative adaptation of RT to a change of RR (2.15 +/- 1% during control). Atenolol increased mean RR (p < 0.001) and decreased relative adaptation of RT (0.22 +/- 0.18%, p < 0.001). The inverse correlation between mean RR and the relative RT adaptation (r = -0.76, p < 0.05) disappeared after atenolol administration. Regarding RT delay, complete adaptation of RT required 3 min; 48 +/- 16% of this adaptation was observed after the first beat and 60 +/- 11% was observed after the 20th. Atenolol attenuated this adaptation during the first six beats following the abrupt cycle length change (p < 0.05). We concluded that the attenuation of RT rate adaptation after atenolol is related to heart rate modulation and to the time delay in RT rate adaptation.

[New markers for the risk of sudden death: analysis of ventricular repolarization]. / Nouveaux marqueurs de risque de mort subite: apport de l'analyse de la repolarisation ventriculaire.

The identification of patients at high risk of sudden cardiac death is one of the greatest challenges for cardiologists. Non-invasive methods have, characteristically, low predictive sensitivities and specificities. The role of abnormalities of ventricular repolarisation (QT interval) in the genesis of ventricular arrhythmias has been well established by experimental data. For this reason, parameters of ventricular repolarisation on the surface electrocardiogram have been proposed. However, taken in isolation, these markers are limited in terms of arrhythmic risk stratification. This report analyses the value of the different parameters of ventricular repolarisation in the identification of high risk: QT dispersion, QT dynamics and T wave alternans. The dispersion of the QT interval is a marker of unhomogenous ventricular depolarisation. This concept must be applied differently in such pathologically dissimilar diseases such as myocardial infarction, cardiomyopathy or the long QT syndrome. Moreover, methodological problems make the interpretation of many experimental studies very delicate. Frequency dependence of the QT helps select high risk patients after myocardial infarction or with dilated cardiomyopathy. A common feature of pathological ventricular myocardium is the more pronounced frequency-dependency of the QT interval. The predictive value of this new index should be evaluated and compared with other non-invasive risk factors in prospective trials. Studies of T wave alternans in selected high risk populations, essentially patients with coronary artery disease and dilated cardiomyopathy, have shown this parameter to be predictive of arrhythmia. The predictive value requires confirmation in much larger populations at lower levels of risk of arrhythmia and sudden death in prospective trials. A new field of research has opened up in the study of ventricular repolarisation. Many studies have been undertaken on the duration of the QT interval, the morphology of the QT (including T wave alternans and post-pause changes) and, finally, the dynamics of the QT interval. By regrouping, analysing and using these data correctly, we should be able to identify new markers of high arrhythmic risk.

Parasympathetic activity during parabolic flight, effect of LBNP during microgravity.

BACKGROUND/HYPOTHESIS: During parabolic flight, in the standing position, changes are partly due to an acute shift in fluid between the lower extremities, the head and the thorax (Vaïda P, et al. J Appl Physiol 1997; 82:1091-7; and Bailliart O, et al. J Appl Physiol 1998; 85:2100-5). We hypothesized that modifications of parasympathetic activity associated with changes in hydrostatic pressure gradients induced by changes in gravity could be detected by analysis of short time periods. METHODS: We assessed heart rate variability (HRV) in 11 healthy volunteers by indices of temporal analysis (NN, SDNN, RMSSD) and normalized indices such as coefficients of variation CV-SDNN and CV-RMSSD and ratio SDNN/RMSSD. A lower body negative pressure (LBNP) at -50 mm Hg was randomly applied during the microgravity phase (0 Gz) to counteract the lack of hydrostatic pressure in the lower part of the body. RESULTS: NN, CV-SDNN and CV-RMSSD decreased during hypergravity phases and increased during microgravity and during early normogravity (1 Gz) period at the end of parabolas. With LBNP changes are less pronounced at 0 Gz and in the 1 Gz post parabolic period. CONCLUSION: We concluded that parasympathetic nervous activity is recordable by temporal analysis of HRV during short periods of time. LBNP applied during 0 Gz phase reduced the parasympathetic activation at 0 Gz and post parabolic 1 Gz.