Walking-adaptability therapy after stroke: results of a randomized controlled trial.

BACKGROUND: The ability to adapt walking to environmental properties and hazards, a prerequisite for safe ambulation, is often impaired in persons after stroke. RESEARCH QUESTION: The aim of this study was to compare the efficacy of two walking-adaptability interventions: a novel treadmill-based C-Mill therapy (using gait-dependent augmented reality) and the standard overground FALLS program (using physical context). We expected sustained improvements for both treatment groups combined but hypothesized better outcomes for C-Mill therapy than the FALLS program due to its expected greater amount of walking practice. METHODS: In this pre-registered single-centre parallel group randomized controlled trial, forty persons after stroke (≥ 3 months ago) with walking and/or balance deficits were randomly allocated to either 5 weeks of C-Mill therapy or the FALLS program. The primary outcome measure was the standard walking speed as determined with the 10-meter walking test (10MWT). Additionally, context-specific walking speed was assessed in environments enriched with either stationary physical context (10MWT context) or suddenly appearing visual images (Interactive Walkway obstacles). The walking-adaptability scores of those enriched walking tests served as secondary outcome measures. Furthermore, a cognitive task was added to all three assessments to evaluate dual-task performance in this context. Finally, the participants' experience and amount of walking practice were scored. The outcome measures were assessed at four test moments: pre-intervention (T0), post-intervention (T1), 5-week post-intervention retention (T2), and 1-year post-intervention follow-up (T3). RESULTS: No significant group differences were found between the interventions for the primary outcome measure standard walking speed, but we found a greater improvement in context-specific walking speed with stationary physical context of the C-Mill therapy compared to the FALLS program at the post-intervention test, which was no longer significant at retention. Both interventions were well received, but C-Mill therapy scored better on perceived increased fitness than the FALLS program. C-Mill therapy resulted in twice as many steps per session of equal duration than the FALLS program. The "change-over-time" analyses for participants of both interventions combined showed no significant improvements in the standard walking speed; however, significant improvements were found for context-specific walking speed, walking adaptability, and cognitive dual-task performance. SIGNIFICANCE: This study showed no between-group differences between the novel treadmill-based C-Mill therapy and the standard overground FALLS program with respect to the primary outcome measure standard walking speed. However, the greater amount of walking practice observed for the C-Mill group, an essential aspect of effective intervention programs after stroke, may underlie the reported increased perceived fitness and observed increased context-specific walking speed for the C-Mill group directly after the intervention. Although the "change-over-time" results for all participants combined showed no improvement in the standard walking speed, context-specific walking speed and walking adaptability showed sustained improvements after the interventions, underscoring the importance of including walking-adaptability training and assessment in rehabilitation post stroke. TRIAL REGISTRATION: The Netherlands Trial Register NTR4030 . Registered 11 June 2013.

Linear mixed-effects models for central statistical monitoring of multicenter clinical trials.

Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this context, we consider the simple case of a continuous variable, and we propose a detection procedure based on a linear mixed-effects model to detect location differences between each center and all other centers. We describe the performance of the procedure as a function of contamination rate and signal-to-noise ratio. We investigate the effect of center size and variance structure and illustrate the use of the procedure using data from two multicenter clinical trials.

Unmappable ventricular tachycardia after an old myocardial infarction. Long-term results of substrate modification in patients with an implantable cardioverter defibrillator.

PURPOSE: The frequent occurrence of ventricular tachycardia can create a serious problem in patients with an implantable cardioverter defibrillator. We assessed the long-term efficacy of catheter-based substrate modification using the voltage mapping technique of infarct-related ventricular tachycardia and recurrent device therapy. METHODS: The study population consisted of 27 consecutive patients (age 68 ± 8 years, 25 men, mean left ventricular ejection fraction 31 ± 9%) with an old myocardial infarction and multiple and/or hemodynamically not tolerated ventricular tachycardia necessitating repeated device therapy. A total of 31 substrate modification procedures were performed using the three-dimensional electroanatomical mapping system. Patients were followed up for a median of 23.5 (interquartile range 6.5-53.2) months before and 37.8 (interquartile range 11.7-71.8) months after ablation. Antiarrhythmic drugs were not changed after the procedure, and were stopped 6 to 9 months after the procedure in patients who did not show ventricular tachycardia recurrence. RESULTS: Median ventricular tachycardias were 1.6 (interquartile range 0.7-6.7) per month before and 0.2 (interquartile range 0.00-1.3) per month after ablation (P = 0.006). Nine ventricular fibrillation episodes were registered in seven patients before and two after ablation (P = 0.025). Median antitachycardia pacing decreased from 1.6 (interquartile range 0.01-5.5) per month before to 0.18 (interquartile range 0.00-1.6) per month after ablation (P = 0.069). Median number of shocks decreased from 0.19 (interquartile range 0.04-0.81) per month before to 0.00 (interquartile range 0.00-0.09) per month after ablation (P = 0.001). One patient had a transient ischemic attack during the procedure, and another developed pericarditis. Nine patients died during follow-up, eight patients due to heart failure and one patient during valve surgery. CONCLUSION: Catheter-based substrate modification using voltage mapping results in a long-lasting reduction of cardioverter defibrillator therapy in patients with multiple and/or hemodynamically not tolerated infarct-related ventricular tachyarrhythmia.

Internal atrial shock delivery by standard diagnostic electrophysiology catheters in goats: effects on atrial electrogram amplitude and tissue architecture.

AIMS: In this study, we evaluated the effects of atrial shock delivered via diagnostic electrophysiology catheters. METHODS AND RESULTS: In 11 anaesthetized goats, decapolar catheters were positioned in the right atrial appendage (RAA) and coronary sinus (CS). Three different catheters and two cardioversion protocols were evaluated. In four goats, 50 J shocks were delivered using catheters with 1 mm electrodes (surface area 70 mm(2)). In 6 goats, catheters with 2 mm electrodes (area 140 mm(2)) were used. In three of the six goats, 50 J shocks were given while in the other 3, 10 J shocks were delivered. In 1 goat 50 J shocks were delivered via 5 mm electrode catheters (area 310 mm(2)). No persisting adverse effects occurred. However, the electrogram amplitude at the RAA and CS decreased by >50-98% (P > 0.01). The amount of amplitude decrease was most pronounced at the CS site and for 50 J shocks. Goats were sacrificed after 9 +/- 1 days. Macroscopy revealed endocardial lesions at the electrode locations. Microscopy showed endocardial thrombosis, and necrosis with formation of granulation tissue. Changes were most marked with diagnostic catheters and 50 J shocks. CONCLUSIONS: Atrial shock delivery via diagnostic catheters causes local ablation lesions. The amount of amplitude decrease, macroscopic and microscopic damages were related to the energy applied and electrode surface area.

Radiofrequency ablation of atrial arrhythmias after previous open-heart surgery.

AIM: To report the results of ablation of atrial arrhythmias (AA) after previous open-heart surgery. METHODS: Nineteen patients [50+/-11 years, 11 women] underwent ablation of symptomatic AAs after previous open-heart surgery. In 11 patients mapping was performed using conventional multielectrode catheters. In the other eight patients CARTO electro-anatomical mapping system was used to supplement conventional mapping. RESULTS: After conventional mapping, 10/11 patients (91%) were found to have typical atrial flutter (AFL). The cavotricuspid isthmus was successfully ablated in these 10 patients. CARTO combined with conventional mapping showed that 7 of 8 patients had one macro-reentry right atrial circuit. The remaining patient had two focal atrial tachycardias. CARTO-guided ablation was successful in all eight patients (100%). After follow-up of 12+/-11 months, 2/18 patients (11%) had recurrence of either the same (n=1) or a new (n=1) AA. CONCLUSIONS: AAs after previous open-heart surgery can be ablated successfully (>90%) with a low recurrence rate (11%) at 1-year follow-up. Typical AFL was found frequently (14/19 patients, 72%). This could be ablated successfully, often, after conventional mapping alone. CARTO helps to uncover peri-scar reentry and guide the ablation by creating a line of block connecting the scar to another landmark (unconventional isthmus).

Transvenous cryoablation of cardiac arrhythmias.

This study reports on the acute and long-term results of cryoablation in patients with supraventricular and ventricular tachycardia. One hundred fifty nine patients with cardiac arrhythmias (147 with supraventricular and 12 with ventricular tachycardia) were consecutively enrolled in our institution to undergo trnasvenous cryoablation with a new cryotechnology system (CryoCor trade mark ). This cryoablation system consists of a console, an articulating arm housing a pre-cooler, and a disposable sterile steerable bipolar 10-fr catheter. The N(2)O is used as a main refrigerant. The acute and chronic outcomes (after 15 months for patients with supraventricular tachycardia and 9 months for patients with ventricular tachycardia) were comparable to those using radiofrequency energy. From this study we concluded that transvenous cryoablation is a safe and effective therapy for the treatment of cardiac arrhythmias.

Biatrial activation in isthmus-dependent atrial flutter.

BACKGROUND: The aim of this study was to determine the biatrial activation pattern in isthmus-dependent atrial flutter (AFL) to understand the functional interatrial connections and the activation pattern of the left atrium (LA). METHODS AND RESULTS: Biatrial activation was performed, using an electroanatomic mapping system, in 10 patients undergoing right atrial isthmus ablation for counterclockwise (n=7) or clockwise (n=3) AFL. The AFL circuit was peritricuspid and propagated slowly (0.5+/-0.2 m/s) through the isthmus. LA was activated by two wave fronts, with discrete breakthroughs in the superior, mid, or inferior atrial septum. The activation of LA overlapped 50+/-16% of the AFL cycle length. In counterclockwise AFL, at least one breakthrough was located in the inferior atrial septum. LA activation began immediately after the exit of the flutter wave from the isthmus and was directed inferosuperiorly in all patients, being synchronous with the atrial septal activation. The septal breakthroughs in patients with clockwise AFL were variably located. The direction of LA activation was superoinferior in 2 and inferosuperior in 1 patient. CONCLUSIONS: The circuit of isthmus-dependent AFL was entirely in the right atrium. LA activation was a bystander and followed trans-septal conduction across the inferior coronary sinus-LA connection, Bachmann's bundle, and/or fossa ovalis.

The effect of incentive spirometry on postoperative pulmonary complications: a systematic review.

OBJECTIVE: To systematically review the evidence examining the use of incentive spirometry (IS) for the prevention of postoperative pulmonary complications (PPCs). METHODS: We searched MEDLINE, CINAHL, HealthSTAR, and Current Contents databases from their inception until June 2000. Key terms included "incentive spirometry," "breathing exercises," "chest physical therapy," and "pulmonary complications." Articles were limited to human studies in English. A secondary search of the reference lists of all identified articles also was conducted. A critical appraisal form was developed to extract and assess information. Each study was reviewed independently by one of three pairs of group members. The pair then met to reach consensus before presenting the report to the entire review group for final agreement. RESULTS: The search yielded 85 articles. Studies dealing with the use of IS for preventing PPCs (n = 46) were accepted for systematic review. In 35 of these studies, we were unable to accept the stated conclusions due to flaws in methodology. Critical appraisal of the 11 remaining studies indicated 10 studies in which there was no positive short-term effect or treatment effect of IS following cardiac or abdominal surgery. The only supportive study reported that IS, deep breathing, and intermittent positive-pressure breathing were equally more effective than no treatment in preventing PPCs following abdominal surgery. CONCLUSIONS: Presently, the evidence does not support the use of IS for decreasing the incidence of PPCs following cardiac or upper abdominal surgery.

Use of a saline-irrigated tip catheter for ablation of ventricular tachycardia resistant to conventional radiofrequency ablation: early experience.

INTRODUCTION: Radiofrequency (RF) catheter ablation of ventricular tachycardia (VT) may fail if the critical isthmus is located intramyocardially or epicardially. The design of a saline-irrigated tip (SIT) catheter (Thermo-Cool, Cordis-Webster) involves active cooling of the tip electrode, which allows creation of larger ablation lesions. METHODS AND RESULTS: Eight patients (6 men, age 59 +/- 12 years) in whom the clinical target VT (cycle length 430 +/- 97 msec) could not be ablated using a conventional 4-mm tip RF ablation catheter underwent additional attempts to ablate this VT using a SIT catheter. Six patients had an old myocardial infarction, 1 patient had a dilated cardiomyopathy, and 1 patient had a structurally normal heart. Ablation of the clinical target VT using a SIT catheter was attempted from the left ventricle in 6 (septal, posterobasal, and inferior: 2 each) and from the right ventricle in 2 patients (both septal), by entrainment (n = 6), activation (n = 1), or pace mapping (n = 1). A mean of 6 +/- 5 (range 2 to 15) pulses were delivered. Target VT ablation was successful in 5 patients (63%). After successful ablation, at a mean follow-up of 6.5 +/- 4 months and while taking antiarrhythmic drugs, all 5 patients were free of VT recurrences. CONCLUSION: The clinical target VT could be ablated using a SIT catheter in 5 (63%) of the 8 patients in whom ablation using a conventional RF catheter was unsuccessful. In the 2 patients with septal VT, a biventricular approach to mapping and ablation was required.

Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long term outcome after right atrial isthmus ablation.

OBJECTIVE: To describe the electrocardiographic and electrophysiological findings of new atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation, and to report the long term results of right atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial flutter. DESIGN: Retrospective analysis. SETTING: Tertiary care academic hospital. PATIENTS: 24 consecutive patients with atrial fibrillation (age 54 (12) years; 5 female, 19 male) developing atrial flutter while taking propafenone (n = 12) or flecainide (n = 12). RESULTS: The ECG was classified as typical (n = 13; 54%) or atypical atrial flutter (n = 8) or coarse atrial fibrillation (n = 3). Counterclockwise atrial flutter was the predominant arrhythmia. Acute success after isthmus ablation was similar in patients with typical (12/13) and atypical (8/8) atrial flutter. After long term follow up (13 (6) months, range 6-26 months), continuation of antiarrhythmic drug treatment appeared to result in better control of recurrences of atrial fibrillation in patients with typical atrial flutter (11/13) than in those with atypical atrial flutter (4/8), but the difference was not significant. Ablation for coarse atrial fibrillation was unsuccessful. CONCLUSIONS: New atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation has either typical or atypical flutter wave morphology on ECG. The endocardial activation pattern and the acute results of ablation suggest that the flutter circuit was located in the right atrium and that the isthmus was involved in the re-entry mechanism. There appeared to be better long term control of recurrent atrial fibrillation in patients with typical (85%) as compared with atypical atrial flutter (50%). Patients developing coarse atrial fibrillation may not be candidates for this strategy.

Comparison of results of an 8-mm split-tip versus a 4-mm tip ablation catheter to perform radiofrequency ablation of type I atrial flutter.

Thirty consecutive patients with type I atrial flutter were randomized to undergo radiofrequency ablation using an 8-mm split-tip versus a 4-mm tip catheter. Procedural success was high in both groups (100% vs 93%). However, requirement of a fewer number of radiofrequency pulses and fluoroscopy time suggests superiority of the 8-mm split-tip over the 4-mm tip ablation catheter.

Initial clinical experience with ambulatory use of an implantable atrial defibrillator for conversion of atrial fibrillation. Metrix Investigators.

BACKGROUND: A recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. METHODS AND RESULTS: An atrial defibrillator was implanted in 105 patients (75 men; mean age, 59+/-12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented "not at all," 10 represented "extremely") after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6+/-1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2+/-2.4 for successful therapy and 4.2+/-2.2 for unsuccessful therapy (P:>0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4+/-3. 3 versus 8.7+/-1.3, P:<0.05). There was no ventricular proarrhythmia observed throughout the course of this study. CONCLUSIONS: Ambulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Decreasing the number of leads required for an implantable atrial defibrillator: use of a new 2-lead system.

BACKGROUND: The purpose of this study was to evaluate the use of a new 2-lead system for detection of atrial fibrillation (AF) and atrial defibrillation. METHODS: In 16 patients undergoing elective cardioversion of AF, a 2-lead system was compared with the conventional 3-lead system in a randomized trial. The new 2-lead system consisted of a catheter with a distal bipolar right ventricular electrode pair and a proximal right atrial shock electrode coil and a separate decapolar defibrillation catheter in the coronary sinus. For the 3-lead system, an additional decapolar catheter was placed in the right atrium. AF and sinus rhythm signal amplitude detection and atrial defibrillation threshold (ADFT) were compared in each patient with both systems. RESULTS: Successful defibrillation was obtained in all patients. ADFT for the 2-lead system was significantly higher compared with the 3-lead system (370 +/- 112 vs 316 +/- 100 V, P < .05; 9.3 +/- 5.2 vs 6.8 +/- 4.2 J, P < .05). In contrast, there was an increase in impedance for the 3-lead system (77 +/- 16 ohms vs 68 +/- 13 ohms; P < .05). AF had a lower signal amplitude compared with sinus rhythm for both systems (P < .05), and the 2-lead system had a lower signal amplitude compared with the 3-lead system for both rhythms (P < .05). CONCLUSION: The use of a 2-lead system with this configuration is not superior to the 3-lead system regarding AF signal amplitude detection and ADFT. Further study is needed with implantable-quality leads in place of the temporary catheters used in this study.

Management of atrial arrhythmias secondary to severe congenital heart disease with the Atrioverter.

An atrial defibrillator was implanted in a patient with congenitally corrected transposition of the great arteries, associated cardiac abnormalities, and persistent atrial arrhythmias. During a 15-month follow-up, 14 of 20 spontaneous episodes of his arrhythmias were successfully treated with the device. Two of these episodes were converted to sinus rhythm during ambulatory use of the device. Successful use of the device required implantation of a third defibrillation lead in the persistent left-sided superior caval vein and rigid control of congestive heart failure. An atrial defibrillator may be a valid treatment option in patients with congenital heart disease crippled by atrial fibrillation.