Epidemiological Profile of Atrial Fibrillation: A Contemporary Perspective

The filling of the ventricle (diastole) is followed by ventricular contraction (systole) to provide an adequate cardiac output during both rest and exercise to meet the body’s metabolic demands. Systole and diastole affect each other in an intimate manner to accomplish this goal. This chapter describes how to determine normal and abnormal left ventricular (LV) filling patterns and to recognize when abnormal LV relaxation, compliance, and filling pressures are present using two-dimensional (2-D) and Doppler technique of mitral and pulmonary venous flow velocity variables. When needed additional information such as color M mode, Doppler tissue imaging, and altering loading conditions help this analysis. By identifying the abnormalities present, and which is predominant, an individualized treatment plan can be devised for cardiac patients.

Dronedarone, a multiple ion channel blocker is prescribed for the treatment of paroxysmal and persistent atrial fibrillation. While dronedarone does not precipitate toxicities like its predecessor amiodarone, its clinical use has been associated with idiosyncratic hepatic and cardiac adverse effects and drug–drug interactions (DDIs). As dronedarone is a potent mechanism-based inactivator of CYP3A4 and CYP3A5, a question arose if it exerts a similar inhibitory effect on CYP2J2, a prominent cardiac CYP450 enzyme. In this study, we demonstrated that CYP2J2 is reversibly inhibited by dronedarone (K_i = 0.034 μM), amiodarone (K_i = 4.8 μM) and their respective pharmacologically active metabolites namely N-desbutyldronedarone (NDBD) (K_i = 0.55 μM) and N-desethylamiodarone (NDEA) (K_i = 7.4 μM). Moreover, time-, concentration- and NADPH-dependent irreversible inactivation of CYP2J2 was investigated where inactivation kinetic parameters (K_I, k_inact) and partition ratio (r) of dronedarone (0.05 μM, 0.034 min⁻¹, 3.3), amiodarone (0.21 μM, 0.015 min⁻¹, 20.7) and NDBD (0.48 μM, 0.024 min⁻¹, 21.7) were observed except for NDEA. The absence of the characteristic Soret peak, lack of recovery of CYP2J2 activity upon dialysis, and biotransformation of dronedarone and NDBD to quinone-oxime reactive metabolites further confirmed the irreversible inactivation of CYP2J2 by dronedarone and NDBD is via the covalent adduction of CYP2J2. Our novel findings illuminate the possible mechanisms of DDIs and cardiac adverse effects due to both reversible inhibition and irreversible inactivation of CYP2J2 by dronedarone, amiodarone and their active metabolites.

Contrast-induced nephropathy (CIN) is an iatrogenic problem in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Atrial fibrillation (AF) may also contribute to impaired kidney function. Several factors may contribute to the development of CIN. In patients with STEMI, concomitant AF is associated with higher in-hospital/follow-up mortality and morbidity. Therefore, we aimed to investigate the relationship between AF and CIN developments.

In this study, 650 consecutive STEMI patients treated with PPCI were enrolled. Patients with AF at admission who did not achieve a sinus rhythm during 48 h after hospitalization were defined as AF patients. CIN was defined by an increase in serum creatinine by >25% or 0.5 mg/dL within 72 h following contrast media exposure.

Our patients were divided into two groups based on whether they had AF, and although warfarin usage was different, the other parameters were similar between the groups. When our patients were grouped according to CIN development [group 1: CIN (+), group 2: CIN (−)], creatinine levels prior to PPCI (p = 0.020), estimated glomerular filtration rate (eGFR) prior to PPCI (p < 0.001), left ventricular ejection fraction (LVEF) (p = 0.011), AF (p < 0.001), and warfarin usage (p = 0.016) were different between the two groups. We also performed multivariate logistic regression analyses and found that AF [odds ratio (OR), 6.945; 95% confidence interval (CI), 2.789–17.293; p < 0.001], eGFR (OR, 0.973; 95% CI, 0.957–0.989; p = 0.001), and LVEF (OR, 0.963; 95% CI, 0.935–0.991; p = 0.010) independently predicted CIN development in patients with STEMI.

The risk factors for CIN are multifactorial and identifying high-risk patients is the most important step for prevention. In addition to traditional risk factors, AF can contribute to CIN development in patients with STEMI.

Atrial fibrillation (AF) is the most frequent heart rhythm disorder in the general population and contributes not only to a major deterioration in quality of life but also to an increase in cardiovascular morbimortality. The onset of AF in the acute phase of myocardial infarction (MI) is a major event that can jeopardize the prognosis of patients in the short-, medium- and long-term, and is a powerful predictor of a poor prognosis after MI. The suspected mechanism underlying the excess mortality is the drop in coronary flow linked to the acceleration and arrhythmic nature of the left ventricular contractions, which reduce the left ventricular ejection fraction. The principal causes of AF-associated death after MI are linked to heart failure. Moreover, the excess risk of death in these heart failure patients has also been associated with the onset of sudden death. Whatever its form, AF has a major negative effect on patient prognosis. In recent studies, symptomatic AF was associated with inhospital mortality of 17.8%, to which can be added mortality at 1 year of 18.8%. Surprisingly, silent AF also has a negative effect on the prognosis, as it is associated with an inhospital mortality rate of 10.4%, which remains high at 5.7% at 1 year. Moreover, both forms of AF are independent predictors of mortality beyond traditional risk factors. The frequency and seriousness of silent AF in the short- and long-term, which were until recently rarely studied, raises the question of systematically screening for it in the acute phase of MI. Consequently, the use of continuous ECG monitoring could be a simple, effective and inexpensive solution to improve screening for AF, even though studies are still necessary to validate this strategy. Finally, complementary studies also effect of oxidative stress and endothelial dysfunction, which seem to play a major role in triggering this rhythm disorder.

La fibrillation atriale (FA) est le plus fréquent des troubles du rythme cardiaque dans la population générale et contribue non seulement à une détérioration importante de la qualité de vie mais aussi à une augmentation de la morbi-mortalité cardiovasculaire. L’apparition de la FA dans la phase aiguë de l’infarctus du myocarde (IDM) est un événement majeur qui peut mettre en péril le pronostic des patients à court, moyen et long termes, et est un puissant facteur prédictif de mauvais pronostic après un IDM. Le mécanisme sous-jacent qui pourrait expliquer la surmortalité est la chute du débit coronaire lié à l’accélération et au caractère arythmique des contractions du ventricule gauche, qui réduisent la fraction d’éjection ventriculaire gauche. Les principales causes de décès associées à la FA après un IDM sont liées à l’insuffisance cardiaque. De plus, le sur-risque de décès chez ces patients insuffisants cardiaques est également associé à la survenue d’une mort subite par troubles du rythme ventriculaire graves. Quelle que soit sa forme, la FA a un effet négatif important sur le pronostic du patient. Dans des études récentes, la FA symptomatique a été associée à une mortalité intra-hospitalière de 17,8 %, à laquelle on peut ajouter la mortalité à 1 an de 18,8 %. De manière très intéressante, la FA silencieuse a également un effet négatif sur le pronostic des patients après un IDM, avec une mortalité intra-hospitalière de 10,4 % et qui reste élevée à un an à 5,7 %. De plus, la survenue d’une FA quelle que soit sa forme est un facteur prédictif indépendant de la mortalité au-delà de facteurs de risque traditionnels. La fréquence de survenue et l’impact pronostic à court et long termes des épisodes silencieux de FA, qui n’avaient jusqu’à été que rarement étudiés, soulèvent la question du dépistage systématique de la Fa silencieuse à la phase aiguë de l’IDM. Par conséquent, l’utilisation du monitoring en continu de l’ECG pourrait être une solution simple, efficace et peu coûteuse pour améliorer le dépistage des épisodes de FA silencieuse, même si des études sont encore nécessaires pour valider cette stratégie. Enfin, des études complémentaires semblent également prouver l’implication du stress oxydatif et de la dysfonction endothéliale, qui semblent jouer un rôle majeur dans le déclenchement de ce trouble du rythme.

La fibrillation atriale est une situation clinique qui peut exposer à un risque de complications thromboemboliques. Plusieurs marqueurs biologiques ont été testés afin d’affiner la stratification de ce risque. Le but de cette étude est d’étudier l’intérêt du dosage des d-dimères dans cette pathologie. L’étude était prospective, intéressant 50 malades et 19 témoins colligés au service de cardiologie de l’hôpital Mongi Slim entre le 1^er juillet–1^er novembre 2012. Le dosage des d-dimères a été réalisé sur mini-VIDAS^® et analysé en fonction des données cliniques, échographiques et biologiques. L’âge moyen des patients était de 61,8 ± 10,6 ans. Le score CHA2DS2-VASc moyen était de 2,58 ± 1,31. Le taux moyen des d-dimères des patients était de 590 ± 506 ng/mL et de 225,26 ± 112,95 ng/mL chez les témoins (p = 0,02). Il n’a pas été retrouvé de différence significative entre le taux des d-dimères selon l’âge, le sexe, le type et l’étiologie de la fibrillation atriale, le score CHA2DS2-VASc, la surface de l’oreillette gauche et la présence d’un thrombus intra-auriculaire gauche. Le taux des d-dimères était significativement plus élevé chez les patients sous acénocoumarol ayant un INR < 2 par rapport à ceux ayant un INR ≥ 2 (p = 0,004). Une valeur seuil de positivité du taux des d-dimères (300 ng/mL) a été déterminée permettant de distinguer significativement les patients des témoins (p < 0,001). Le dosage des d-dimères pourrait permettre d’identifier les patients en fibrillation atriale avec un état d’hypercoagulabilité. Il pourrait être complémentaire au dosage de l’INR dans la surveillance du traitement anticoagulant et ceux en permettant d’affiner le risque thrombogène.

Atrial fibrillation can expose to thrombo-embolic complications. Many biomarkers have been tested to refine the stratification of thrombo-embolic risk. The study aim was to assess the interest of the d-dimer testing in this pathology. We conducted a prospective observational study including 50 cases and 19 controls, enrolled at the cardiology department of the Mongi Slim Hospital, from July to November 2012. The d-dimer assay was performed on mini-VIDAS^® and analyzed according to clinical, echocardiographic and biological data. The mean age of patients was 61.8 ± 10.6 years. The mean CHA2DS2-VASc score was 2.58 ± 1.31. The average of D-dimer levels was 590 ± 506 ng/ml in patients and 225.26 ± 112.95 ng/ml in controls (P = 0.02). No significant difference has been found between the d-dimer level and age, sex, type and etiology of atrial fibrillation, the CHA2DS2-VASc score, the left atrial surface. Among patients on acenocoumarol, d-dimer levels was significantly higher in patients with an INR < 2 compared to those with an INR ≥ 2 (P = 0.004). We identified a positive d-dimer threshold (300 ng/ml) in patients distinguishing them significantly with controls (P < 0.001). In conclusion, the measurement of d-dimers could help clinicians to identify patients with atrial fibrillation having an increased coagulability and, therefore, an increased thrombo-embolic risk. It could be complementary to the determination of INR in monitoring anticoagulation therapy: d-dimers level refines the thrombo-embolic risk and INR measurement assesses the level of anticoagulation and the bleeding risk.