Recent Advances in Drug Therapy for Atrial Fibrillation

Despite the major new insights into our knowledge of the mechanisms underlying initiation and perpetuation of atrial fibrillation (AF) gained in the last decade, the treatment of this common arrhythmia remains unsatisfactory in many patients. Although several new treatment modalities (e.g., internal cardioversion, pulmonary vein ablation, preventive pacing) have been developed, pharmacologic therapy remains the first-line therapy in most patients with AF. As illustrated by recent trials comparing rhythm control and rate control, current antifibrillatory drugs are hampered by a relatively low success rate in maintaining long-term sinus rhythm and the occurrence of proarrhythmic and other adverse events. This article discusses currently available antiarrhythmic drugs for rhythm and rate control, with special emphasis on more recently developed drugs and drugs still under development. Selective blockers of atrial ion channels (I _Kur and I _K.ACh ), multi-ion channel blockers, and selective A ₁ -adenosine receptor antagonists are examples of the newer antiarrhythmic drugs that are expected to be more effective and safer than those currently available. (J Cardiovasc Electrophysiol, Vol. 14, pp. S40-S47, September 2003, Suppl.)     

Sustained Monomorphic Ventricular Tachycardia: A Single Electrocardiographic Expression of Different Patterns of Reentry

Sustained monomorphic ventricular tachycardia (SMVT) can be the electrocardiographic expression of a reentrant impulse in the ventricles. In this study we analyzed the different types of reentry that might lead to SMVT, Methods: The pattern of activation of 73 episodes of SMVT induced in thin sheets of epicardium in 50 Langendorff perfused rabbit hearts were visualized with high resolution epicardial mapping (248 points). Results: Five different patterns of reentry resulting in SMVT were identified: (1) Single-loop reentry around a fixed obstacle (n = 40); (2) Single-loop reentry around a functional arc of conduction block (n = 17); (3) Double-wave reentry around a fixed obstacle (n = 9); (4) Figure-of-eight reentry around two areas of functional block (n = 5); and (5) Multiple synchronized circuits around multiple areas of functional block (n = 2), Conclusion: SMVT is a single electrocardiographic expression of different patterns of reentry. Accurate mopping is mandatory to identify the reentrant pathway and the pathophysiological substrate of the arrhythmia.     

Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross-sectional study

In a prospective investigation, a large kindred (twenty-one subjects) with unexplained association of familial hypocalciuric hypercalcaemia and idiopathic interstitial lung disease was studied. Serum calcium was increased in fifteen patients (the youngest being 7 years old) and was associated with hypo- or normocalciuria. The abnormalities were not age-dependent. The serum concentrations of parathyroid hormone, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and calcitonin were normal. In twelve patients the diffusing capacity (DLCO) and/or DLCO per unit lung volume was less than 75% predicted. This was often accompanied by a vital capacity of less than 80% predicted, and increased Tiffeneau index, and a reticulo-micronodular pattern with high diaphragm on chest X-ray. The decrease in DLCO was more pronounced in older non-smoking as well as smoking subjects (P less than 0.02) suggesting a progressing interstitial disease with age. The fibrosing alveolitis, which had been confirmed by open lung biopsy in three subjects, could not be attributed to sarcoidosis, collagen-vascular disease, or exogenous causes. The disturbances in the calcium homeostasis and in the diffusing capacity of the lung coexisted in seven of the twenty-one patients. Apparently, both abnormalities were inherited following an autosomal-dominant pattern but with a different penetration in each person, and seemed not be causally related to each other.     

Does the heart know what the ears hear? A heart rate analysis of auditory selective attention

Between- and within-channel auditory selective attention were examined by presenting subjects with tone pips randomly to opposite ears; some pips had a slightly different pitch. Subjects were instructed to count rare, deviant tone pips at one ear and ignore all input to the other ear. Heart rate was sampled twice: once for the attended tone pips and once for the nonattended stimulus series. Heart rate responded differently to attended tone pips. While subjects were waiting for the rare stimulus to occur, heart rate slowed until the deviant stimulus was detected, which was followed by heart rate acceleration. Anticipatory heart rate deceleration was largely absent for nonatended series, and rare tone pips presented at the nonattended ear were not followed by acceleratory recovery. All tone pips elicited cardiac cycle time effects, that is, stimuli presented at short delays after the R wave prolonged the concurrent interbeat interval more than stimuli presented later. The cardiac cycle time effect was not altered by stimulus relevance (attended vs. nonattended) or significance (standard vs. rare). These results suggest that all stimuli receive preliminary perceptual analysis, but only attended stimuli are processed for further evaluation.     

Heart rate and sustained attention during childhood: Age changes in anticipatory heart rate, primary bradycardia, and respiratory sinus arrhythmia

This study examined age changes in three aspects of heart rate responsivity elicited in an auditory oddball task; anticipatory heart rate change, primary bradycardia, and respiratory sinus arrhythmia. Three age groups (5-, 7-, and 9-year-old boys) were presented with series of target (15%) and standard (85%) tones. The results were consistent with the findings reported previously in the adult literature. Heart rate decreased in anticipation of the target tone. The morphology of anticipatory deceleration was somewhat different for the 5-year-olds compared to the older children. Stimuli presented during the early part of the cardiac cycle induced added deceleration, but this primary bradycardia did not differ between age groups. Respiratory sinus arrhythmia did not discriminate between age groups but was suppressed during the performance of the oddball task relative to base level. It was concluded that these three aspects of heart rate responsivity show developmental constancy rather than change.     

Variations in Human Atrial Flutter Cycle Length Induced by Ventricular Beats: Evidence of a Reentrant Circuit with a Partially Excitable Gap

Variations in Atrial Flutter Cycle Length. Introduction : The purpose of this investigation was to study the mechanisms responsible for small variations in atrial flutter cycle lengths. Methods and Results : In a study group of 11 patients with common atrial flutter, atrial electrograms were recorded from an intraesophageal lead together with a surface lead (V₁). Upon the onset of the QRS complex, atrial flutter intervals consistently increased by an average of 1.8% (SD± 0.9; P <0.01) and subsequently decreased by 2.1% (SD ± 0.8; P <0.01) before returning to the average flutter rate. Carotid sinus massage, which temporally prevented ventricular activation, markedly reduced the variations in atrial flutter intervals. Ventricular pacing at different rates clearly demonstrated that the pattern in atrial flutter intervals was coupled to the moment of ventricular contraction. The hypothesis was formulated that these periodic variations in atrial flutter intervals following a ventricular contraction were caused by the influence of stretch of the atrial myocardium on the conduction properties of a circulating impulse in the atrium. The secondary decrease in flutter rate could be explained if a partial excitable gap is assumed between head and tail of the circus movement. This hypothesis was tested in a simulation study, which revealed that the alternation in intervals as found in patients could only be reproduced if the excitable gap in the circus movement was partially excitable. Conclusion : In conclusion, the analysis of variations in atrial flutter cycle lengths points to a mechanism of circus movement with a partially excitable gap in common atrial flutter.     

The Impact of New and Emerging Clinical Data on Treatment Strategies for Atrial Fibrillation

AF Treatment Strategies . Introduction: The Atrial Fibrillation (AF) Exchange Group, an international multidisciplinary group concerned with the management of AF, was convened to review recent advances in the field and the potential impact on treatment strategies. Methods: Issues discussed included epidemiology and the impact of the rising incidence of AF on health care systems, developments in pharmacological and surgical interventions in the management of arrhythmias and thromboprophylaxis, the potential to affect treatment strategies, and barriers to implementing them. Results: The incidence of AF and the associated burden on health care systems are increasing with aging populations, prevalence of comorbidities and more effective treatment of cardiovascular diseases. Advances in available medical treatments, in particular dronedarone and dabigatran, with other products in development, offer the possibility of changes in treatment paradigms and a greater emphasis on reducing hospitalizations and improvement in long‐term outcomes instead of a symptom/safety‐driven approach in which the priority is symptom suppression without provoking drug toxicity. Developments in catheter ablation techniques may mean that, in experienced centers, ablation may be offered as first‐line treatment in selected patient populations. Barriers to optimal treatment include underdiagnosis, lack of recognition as a serious condition and as a risk factor for stroke, limited access to care, inadequate implementation of guidelines, and poor adherence to treatment. Conclusions: The focus of the management of AF may be changing as a consequence of new treatments based on the outcome improvements they offer. However, the benefits will not be fully realized if guidelines and guidance are not observed in routine clinical practice. (J Cardiovasc Electrophysiol, Vol. 21, pp. 946‐958, August 2010)     

Susceptibility to Atrial Fibrillation:

Propensity for Extrastimulus to Induce AF. Introduction : The development of susceptibility to atrial fibrillation (AF) is a common consequence of many forms of cardiovascular disease, especially heart failure. In this study we used a sheep model of pacing-induced stable early heart failure to describe, quantify, and relate the level of susceptibility to AF to changes in structural and electrophysiologic parameters.
Methods and Results : Epicardial electrodes were implanted on the atria and right ventricles of nine sheep. The AF thresbold, atrial vulnerability period, atrial effective refractory period (ERP), and interatrial conduction time were examined during control and over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA) area and left ventricular (LV) fractional shortening were monitored using echocardiography. There were significant increases in LA susceptibility to AF (P < 0.0003), LA area (P < 0.0002), and LA FRP400 (P < 0.0002). Rate of increase in LA area was related positively to AF susceptibility (P = 0.02) and inversely to LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of control value (P < 0.00001). No changes were observed in right atrial electrophysiology.
Conclusion : In this study, susceptibility (the ability of an extrastimulus to induce AF) was rigorously measured within a predetermined format. Significant relationships were found to exist between susceptibility, certain of the observed changes in atrial electrophysiology and structure.