Cinétiques de la fréquence cardiaque et de la repolarisation ventriculaire durant l’effort et la récupération

Lors des variations normales de la fréquence cardiaque, notamment durant l’effort et la récupération, l’intervalle QT s’adapte à la durée du cycle cardiaque (RR) selon deux processus : la dépendance QT/RR qui définit la relation entre le RR et le QT à l’état stable, et l’hystérésis QT/RR qui définit la cinétique de l’adaptation du QT entre deux états stables. Plusieurs approches ont été suggérées pour quantifier ces deux processus. Il apparaît que la dépendance QT/RR autant que l’hystérésis QT/RR sont hautement individuels et il a été avancé que certains profils de dépendance ou d’hystérésis QT/RR étaient associés à un mauvais pronostic chez des patients cardiaques. Ces descripteurs de la relation QT/RR varient également entre des sujets apparemment en santé, et bien qu’il semble plausible que ces différences s’expliquent par des variations de la modulation autonome, ce sujet a été pratiquement inexploré. Les travaux présentés dans le cadre de cette thèse visent à définir la réponse normale de l’intervalle QT lors de l’effort et de la récupération, et à caractériser l’adaptation de cette réponse chez des sujets entraînés. L’existence de nombreuses approches présentant de grandes disparités nous a conduits à réaliser une revue systématique de littérature portant sur les méthodes de quantification de l’hystérésis QT/RR et visant à spécifier les limites inhérentes aux méthodes documentées ainsi qu’à déterminer la méthode la plus appropriée pour comparer l’hystérésis entre des conditions où les registres de fréquences cardiaques observées diffèrent. Une deuxième revue systématique a identifié l’ensemble des conditions cliniques dans lesquelles l’hystérésis QT/RR a été mesurée. Il en ressort qu’une hystérésis exagérée pourrait être un prédicteur de mortalité arythmique dans certaines populations, un marqueur d’ischémie durant un test d’effort, et une manifestation du syndrome du QT long. Toutefois, ces preuves d’associations tiennent sur peu d’études et devront être confirmées par des études de plus grande ampleur utilisant des méthodes reproductibles permettant de distinguer l’hystérésis QT/RR de la dépendance QT/RR. Une étude a été conduite chez des hommes en santé afin de déterminer si la cinétique du RR et l’hystérésis QT/RR variaient chez un même sujet entre des protocoles d’effort impliquant des mécanismes de modulation autonome différents. Les résultats démontrent que la cinétique du RR et l’hystérésis QT/RR sont plus lents en récupération qu’à l’effort et que la cinétique du RR est plus lente lorsque l’exercice ou la récupération est amorcé depuis une fréquence cardiaque plus élevée. Cette étude suggère aussi que la présomption habituelle selon laquelle l’hystérésis QT/RR demeure constante chez un individu est inappropriée. Il apparaît que l’hystérésis est exagérée lors d’efforts de faible intensité initiés depuis le repos par rapport aux autres conditions étudiées. Également, l’étude indique que l’estimation de la cinétique individuelle du RR et du QT est plus fiable lorsqu’elle inclut des mesures obtenues à des intensités d’effort relativement élevées que lorsqu’elle se limite à des données de faible intensité. Une dernière étude a comparé la dépendance QT/RR, la cinétique du RR et l’hystérésis QT/RR entre des hommes entraînés en endurance et des hommes modérément actifs, évalués lors d’efforts d’une même intensité relative. Cette étude confirme les résultats antérieurs selon lesquels la cinétique du RR est accélérée chez les hommes entraînés, autant à l’effort qu’en récupération. De plus, les résultats indiquent une prolongation faible mais significative de l’intervalle QT chez les athlètes, indépendante de la fréquence cardiaque, et une augmentation de la pente QT/RR. Toutefois, aucune modification significative de l’hystérésis QT/RR n’a été identifiée chez ces sujets. Dans l’ensemble, les travaux réalisés démontrent que les cinétiques du RR et du QT varient chez un même sujet et témoignent vraisemblablement de mécanismes différents de la modulation autonome cardiaque selon les conditions d’effort et de récupération. Chez des individus entraînés en endurance, la cinétique de la fréquence cardiaque est accélérée et on observe également une faible prolongation de la repolarisation et un accroissement de sa dépendance à la fréquence cardiaque.During physiological heart rate variations in the course of exercise and recovery, the QT interval adapts to cardiac cycle length (RR) according to two distinct processes: QT/RR dependency which describes the steady-state relationship between QT and RR intervals, and QT/RR hysteresis which describes the time course of QT accommodation between steady-state conditions. Several approaches were suggested to quantify these two processes. It appears that both QT/RR dependency and QT/RR hysteresis are highly individual and it was put forward that certain profiles of QT/RR dependency and hysteresis could be useful risk predictors in cardiac patients. However, these descriptors of the QT/RR relationship remain largely variable among healthy subjects. While it is plausible that such inter-individual discrepancies are explained by variations of cardiac autonomic modulation, very few studies have addressed this question. The work conducted in this thesis aims to define the normal response of the QT interval during exercise and recovery and to characterize adaptations of this response in endurance-trained individuals. A systematic review of the literature addressing methods of QT/RR hysteresis estimation is reported. The review highlights the inherent limits of reported approaches and a theoretical comparison of methods suggests that one procedure, namely estimation of the memory in the modelled QT/RR relationship, is superior for comparison of QT/RR hysteresis between conditions where the range of observed RR intervals varies. A second systematic review was conducted with the aim of identifying clinical conditions in which QT/RR hysteresis was examined. It emerges from this review that an increased QT/RR hysteresis could be a predictor of severe arrhythmia, a marker of exercise-induced myocardial ischemia and a feature of the long QT syndrome. However, the proofs of such associations are rather weak and would need to be confirmed by larger studies using reliable methods that can differentiate QT/RR hysteresis from QT/RR dependency. A study was conducted in healthy men in order to determine if RR kinetics and QT/RR hysteresis varied in the same subject between exercise protocols implying different mechanisms of autonomic modulation. The results demonstrate that both RR kinetics and QT/RR hysteresis are slower during recovery compared to exercise, and that RR kinetics is slower when exercise or recovery is initiated from a higher baseline heart rate. This work also suggests that the usual assumption that QT/RR hysteresis remains invariant in a same individual is incorrect. It appears that hysteresis is larger in the transition from rest to low intensity exercise compared to other investigated conditions. In addition, our results show that quantification of individual RR and QT kinetics is more reliable when it is computed from recordings including exercise data at moderate intensities compared to estimations relying solely on data recorded during low intensity exercise. The last study aimed to compare QT/RR dependency, RR kinetics and QT/RR hysteresis between endurance-trained and moderately active young men, evaluated during exercise at identical relative work outputs. The study corroborates previous findings that RR kinetics is accelerated in endurance-trained men, both during exercise and recovery. In addition, the study reveals a small but significant rate-independent QT prolongation in athletes and an increased steady-state QT/RR slope. However, no significant modification of QT/RR hysteresis was observed in these subjects. Overall, this work identifies within-subject variations of RR and QT kinetics, likely explained by varying mechanisms of autonomic cardiac modulation across investigated conditions. In endurance-trained men, heart rate kinetics is accelerated while repolarisation is protracted and its heart rate dependency is increased

Cardiac Arrhythmias

The most intimate mechanisms of cardiac arrhythmias are still quite unknown to scientists. Genetic studies on ionic alterations, the electrocardiographic features of cardiac rhythm and an arsenal of diagnostic tests have done more in the last five years than in all the history of cardiology. Similarly, therapy to prevent or cure such diseases is growing rapidly day by day. In this book the reader will be able to see with brighter light some of these intimate mechanisms of production, as well as cutting-edge therapies to date. Genetic studies, electrophysiological and electrocardiographyc features, ion channel alterations, heart diseases still unknown , and even the relationship between the psychic sphere and the heart have been exposed in this book. It deserves to be read

QT Variability and Other Electrocardiographic Predictors of Sudden Cardiac Death

This thesis investigates sudden cardiac death, focusing of QT variability, heart-rate variability and other electrocardiographic markers. Topics include: - Normal values for heart-rate variability - Normal values for QT variability - The association of QT variability with sudden cardiac death - The association of QT variability with Heart Failure - The association of thyroid function and Sudden cardiac death - The association of thyroid function with QT variability - The association of COPD with sudden cardiac deat

THE EFFECT OF ETHNICITY AND BODY SIZE ON THE ATHLETE’S HEART AND THEIR IMPACT ON CARDIOVASCULAR PRE-PARTICIPATION SCREENING

In response to the augmented haemodynamic load placed upon the heart by intense and prolonged exercise, various forms of physiological remodelling are elicited. The resultant cardiac structural, functional and electrical adaptations are coined the athlete’s heart. Due to the nature of the remodelling, in some cases these adaptations may however overlap with the diagnostic criteria for varying pathological conditions, often related to sudden cardiac death. Several variables are associated with the athlete’s heart including age, sex, sport, body size, and ethnicity. Ethnicity is of particular importance as athletes of an African/Afro-Caribbean ethnicity demonstrate a greater prevalence of abnormal changes suggestive of pathology. There is however paucity in the literature of the athlete’s heart among other ethnicities. For this reason Study 1 investigated the impact of Arabic ethnicity upon the structure, function and electrophysiology of the heart in male athletes. Study 1 identified that while Arabic athletes had larger hearts than Arabic controls, they had significantly smaller hearts than their Black and Caucasian athletic counterparts. While Black athletes had a significantly greater prevalence of training unrelated/abnormal ECG findings, Arabic and Caucasian both had similar levels of training unrelated/abnormal findings, suggesting the European Society of Cardiology guidelines for ECG interpretation in athletes are applicable for the ethnicity.Study 2 investigated another important facet of the athlete’s heart, which is body size. Study 2 identified that while there was a progressive relationship between body size and cardiac dimensions, the previously identified upper limits of cardiac structural remodelling were applicable even among those with a body surface area (BSA) over 2.3m2. Among the cohort of athletes with a BSA >2.3m2, Black athletes demonstrated significantly greater wall thickness’ than Caucasian and Arabic athletes.The second aspect to the thesis highlighted how the findings of Study 1 and 2 impact upon pre-participation screening. While debate still exists around the most effective methodology to screen for pathological cardiac conditions, several organisations mandate the use of the echocardiography alongside the resting 12-Lead ECG. Study 3 established that should echocardiography be limited to use as a follow up investigation, significant cost benefits could be elicited (47% reduction). The premise of this significant cost reduction was that no pathological case was identified by echocardiography in isolation. While still found to be useful in confirming pathology, significantly, in our study the investigation failed to identify two cases of hypertrophic cardiomyopathy.Study 4 investigated the implications of adopting modified ECG interpretation guidelines in light of the criticism that ECG screening should be avoided due to a high false positive rate. Utilising an ethnically diverse cohort, Study 4 demonstrated that using the ‘Refined’ criteria reduced the false positive rate from 22% when using the 2010 ESC guidelines to 5%. Importantly both criteria achieved 100% sensitivity, highlighting the importance of the ECG in cardiovascular screening