Continuous daily assessment of multiple sclerosis disability using remote step count monitoring.

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p < 0.01). Lower average daily step count was associated with greater disability on the Expanded Disability Status Scale (EDSS) (p < 0.001). Within each EDSS category, substantial variability in step count was apparent (i.e., EDSS = 6.0 range 1097-7152). Step count demonstrated moderate-strong correlations with other walking measures. Lower average daily step count is associated with greater MS disability and captures important variability in real-world walking activity otherwise masked by standard disability scales, including the EDSS. These results support remote step count monitoring as an exploratory outcome in MS trials.

Inhibition of the Na(+)/H(+) exchanger delays the development of rapid pacing-induced atrial contractile dysfunction.

BACKGROUND: Atrial mechanical stunning due to atrial fibrillation may persist after restoration of sinus rhythm. Although the mechanism of rapid rate-related contractile dysfunction remains unknown, ischemia, pH changes, and calcium overload have been postulated as potential mechanisms. We hypothesized that blockade of the Na(+)/H(+) exchanger (NHE) would alter atrial contractile dysfunction from rapid rates. METHODS AND RESULTS: Twenty-three anesthetized dogs were studied and subjected to 5 hours of rapid right atrial pacing. Ten received an inhibitor of the NHE, 10 received saline, and 3 received nifedipine. All animals underwent placement of 2 sonomicrometers on the left atrium, transesophageal echocardiography, and invasive hemodynamic monitoring. All measurements were made in sinus rhythm. Except for baseline and postdrug measurements, reduction in left atrial fractional shortening was significantly less at all time points in the NHEI group than in the control and nifedipine groups (P:=0.05). The percent change from baseline of left atrial function at all time intervals as assessed by left atrial appendage contraction velocity (LAACV) was significantly less in the NHEI group than in the control (P:=0.05) group. LAACV was significantly preserved at all time intervals (except 300 minutes) in the NHEI group compared with the nifedipine group (P:=0.05). The only significant difference in hemodynamics among the groups was between the control and the nifedipine groups at 30 minutes after drug (P:=0.05). CONCLUSIONS: Treatment with HOE642 significantly blunts the decline in left atrial mechanical function from rapid atrial rates compared with both control and nifedipine-treated groups.

Localization of the origin of arrhythmias for ablation: from Electrocardiography to advanced endocardial mapping systems.

Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra-atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter-based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter-based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed.

Differences in organization between acute and chronic atrial fibrillation in dogs.

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.

Role of the Na(+)/H(+) exchanger in short-term atrial electrophysiological remodeling.

BACKGROUND: The pathophysiology underlying electrophysiological remodeling (ER) from rapid atrial rates is unknown. We tested the hypothesis that activation of the Na(+)/H(+) exchanger (NHE) by ischemia contributes to ER. METHODS AND RESULTS: Twenty-eight dogs were studied under autonomic blockade. In 15 closed-chest dogs, atrial fibrillation was simulated by right atrial pacing at 600 bpm over 5 hours. Of these, 9 (pace/NHEI) received HOE642, a selective inhibitor of the NHE, and 6 (pace/control) received saline. In pace/controls, atrial effective refractory period (AERP) at a drive cycle length (DCL) of 400 ms shortened from 143+/-7 to 118+/-5 ms (1 hour) and to 122+/-17 ms (5 hours). Shortening of AERP was prevented in the pace/NHEI group (P=0.02 compared with pace/controls). At baseline in all 15 dogs, pacing at shorter DCL resulted in shortening of AERP (physiological rate adaptation), which was lost at 5 hours in pace/controls. In pace/NHEI animals, rate adaptation was maintained despite 5 hours of pacing (P=0.02). In 13 other open-chest dogs, right atrial ERP was determined before and after occlusion of the right coronary artery. Five received HOE642 (ischemia/NHEI), 5 saline (ischemia/control), and 3 intravenous glibenclamide. In ischemia/controls, AERP(400) decreased (156+/-30 to 130+/-32 ms). Shortening of AERP was not prevented by glibenclamide (180+/-20 to 153+/-33 ms) but was prevented in ischemia/NHEI dogs (169+/-12 to 184+/-19 ms, P=0.001 compared with ischemia/controls and ischemia/glibenclamide). Rate adaptation was lost in ischemia/controls and preserved in ischemia/NHEI dogs (P=0. 02). CONCLUSIONS: Activation of the NHE is one mechanism underlying short-term ER.

Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation.

BACKGROUND: Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. METHODS AND RESULTS: Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (P=0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (P=0.01). The coefficient of variation of HED retention was also greater in paced animals (P=0.05) and was greater in the right atrium than in the left atrium (P=0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2+/-5 ms) than in the left atrium (85.8+/-5.5 ms) at baseline (P=0.005). AF cycle length did not vary significantly from baseline (97.6+/-13.4 ms) with stellate stimulation (100.5+/-6 ms) but lengthened with propranolol (107.5+/-6.1 ms, P=0.03). CONCLUSIONS: Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing-induced AF on atrial electrophysiology.

A high-temporal resolution algorithm for quantifying organization during atrial fibrillation.

Atrial fibrillation (AF) has been described as a "random" or "chaotic" rhythm. Evidence suggests that AF may have transient episodes of temporal and spatial organization. We introduce a new algorithm that quantifies AF organization by the mean-squared error (MSE) in the linear prediction between two cardiac electrograms. This algorithm calculates organization at a finer temporal resolution. (approximately 300 ms) than previously published algorithms. Using canine atrial epicardial mapping data, we verified that the MSE algorithm showed nonfibrillatory rhythms to be significantly more organized than fibrillatory rhythms (p < .00001). Further, we compared the sensitivity of MSE to that of two previously published algorithms by analyzing AF with simulated noise and AF manipulated with vagal stimulation or by adenosine administration to alter the character of the AF. MSE performed favorably in the presence of noise. While all three algorithms distinguished between low and high vagal AF, MSE was the most sensitive in its discrimination. Only MSE could distinguish baseline AF from AF with adenosine. We conclude that our algorithm can distinguish different levels of organization during AF with a greater temporal resolution and sensitivity than previously described algorithms. This algorithm could lead to new ways of analyzing and understanding AF as well as improved techniques in AF therapy.

Radiofrequency catheter ablation for postinfarct ventricular tachycardia.

Catheter mapping and radiofrequency ablation of postinfarct sustained ventricular tachycardia (VT) remain one of the greatest challenges for the electrophysiologist. Although there were no major breakthroughs during the past year, several refinements and clarifications of existing mapping criteria were published. In addition, initial reports appeared describing new mapping systems and ablation technologies that may significantly impact the way ablation studies are performed as well as the way in which they affect success rates. Uncertainties remain as to how effective catheter ablation will be as a longterm cure for this type of VT. For the foreseeable future, catheter ablation in postinfarct VT will remain adjunctive rather than primary therapy.

Heterogeneous atrial denervation creates substrate for sustained atrial fibrillation.

BACKGROUND: Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. METHODS AND RESULTS: After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation. Dogs then underwent PET imaging with either a sympathetic ([11C]hydroxyephedrine, HED) or parasympathetic (5-[11C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (>60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136+/-17.6 ms) than those same sites in the sham controls (156+/-19.1 ms) (P=0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17+/-8%) than in the nonphenol sites (9+/-9%) (P=0.01). There was a significantly increased dispersion of refractoriness (21+/-6.4 ms in the sham versus 58+/-14 ms in the phenol dogs, P=0.01) as well as dispersion of AF cycle length (49+/-10 ms in the sham versus 105+/-12 ms in the phenol dogs, P=0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake. CONCLUSIONS: Heterogeneous sympathetic atrial denervation with phenol facilitates sustained AF.

Atrial macroreentry involving the myocardium of the coronary sinus: a unique mechanism for atypical flutter.

Atrial flutter involving either clockwise or counterclockwise rotation around the tricuspid annulus utilizing the subeustachian isthmus has been well described. However, macroreentrant atrial circuits in atypical atrial flutter in patients who have not undergone previous surgery or without atrial disease are not well defined. We describe a patient without structural heart disease who presented with an atrial macroreentrant rhythm. Entrainment mapping demonstrated a critical isthmus within the coronary sinus. Activation mapping demonstrated double potential throughout the length of the coronary sinus with disparate activation sequences. A circuit involving the myocardium of the coronary sinus, exiting in the lateral left atrium, down the interatrial septum, and reentering into the coronary sinus was identified. Successful ablation of the rhythm was accomplished by a circumferential radiofrequency application within the coronary sinus.

Acute effects of intraoperative multisite ventricular pacing on left ventricular function and activation/contraction sequence in patients with depressed ventricular function.

INTRODUCTION: We hypothesized that simultaneous right and left ventricular apical pacing would result in improvement in left ventricular function due to improved coordination of segmental ventricular contraction. Structural changes in ventricular muscle present in dilated cardiomyopathy compromise ventricular excitation and mechanical contraction. METHODS AND RESULTS: Eleven patients with depressed left ventricular function having cardiac surgery underwent epicardial multisite pacing with continuous transesophageal echocardiographic imaging. Quantitative measurement of percent fractional area change was performed, and segmental changes in contraction sequence resulting from simultaneous right and left ventricular pacing were assessed by application of phase analysis to recorded transesophageal images. There was no statistically significant difference between the paced QRS duration achieved with simultaneous right and left ventricular apical pacing and the native QRS duration (139+/-39 msec vs 106+/-18 msec, P = NS), but all other paced modes resulted in longer QRS durations. Percent fractional area change improved with simultaneous right and left ventricular apical pacing but not with other paced modes (41.5+/-11.9 vs 34.3+/-9.7, P < 0.01). Phase analysis demonstrated a resequencing of segmental left ventricular activation/contraction when compared to baseline ventricular activation. CONCLUSION: Simultaneous right and left ventricular apical pacing results in acute improvements in global ventricular performance in patients with depressed ventricular function. Improvements may result from pacing-induced global coordination through recruitment of left and right ventricular apical and septal segments critical to effective ventricular contraction.

"Cristal tachycardias": origin of right atrial tachycardias from the crista terminalis identified by intracardiac echocardiography.

OBJECTIVES: We sought to use intracardiac echocardiography (ICE) to identify the anatomic origin of focal right atrial tachycardias and to define their relation with the crista terminalis (CT). BACKGROUND: Previous studies using ICE during mapping of atrial flutter and inappropriate sinus tachycardia have demonstrated an important relation between endocardial anatomy and electrophysiologic events. Recent studies have suggested that right atrial tachycardias may also have a characteristic anatomic distribution. METHODS: Twenty-three consecutive patients with 27 right atrial tachycardias were included in the study. ICE was used to facilitate activation mapping in relation to endocardial structures. A 20-pole catheter was positioned along the CT under ICE guidance. ICE was also used to assist in guiding detailed mapping with the ablation catheter in the right atrium. RESULTS: Of 27 focal right atrial tachycardias, 18 (67%, 95% confidence interval [CI] 46% to 83%) were on the CT (2 high medial, 8 high lateral, 6 mid and 2 low). ICE identified the location of the tip of the ablation catheter in immediate relation to the CT in all 18 cases. The 20-pole mapping catheter together with echocardiographic visualization of the CT provided a guide to the site of tachycardia origin along this structure. Radiofrequency ablation was successful in 26 (96%) of 27 (95% CI 81% to 100%) right atrial tachycardias. CONCLUSIONS: This study demonstrates that approximately two thirds of focal right atrial tachycardias occurring in the absence of structural heart disease will arise along the CT. Recognition of this common distribution may potentially facilitate mapping and ablation of these tachycardias.

The laboratory evaluation and role of catheter ablation for patients with atrial flutter.

The anatomic substrate for atrial flutter has now been recognized, and improved methods for catheter ablation have been developed. Using mapping techniques such as entrainment mapping, recognizing the different types of flutter that can occur, and testing for conduction block with pacing after ablation, long-term cure of atrial flutter can be achieved in most patients with catheter ablation. Not only is catheter ablative cure of atrial flutter the treatment of choice for drug-refractory patients, but also may now be offered as an alternative to drug therapy.