A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease.

People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD.

Targeted neurotechnology restores walking in humans with spinal cord injury.

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study.

BACKGROUND: Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation. METHODS AND RESULTS: A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, -1.6%; lower limit of 1-sided 95% confidence interval, -10.7%; P=0.0073 for noninferiority). When the CF arm was stratified into optimal CF (≥90% ablations with ≥10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively (P=0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P=0.0004 for noninferiority). CONCLUSIONS: The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01278953.

EFFICAS II: optimization of catheter contact force improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation.

AIMS: A challenge of pulmonary vein isolation (PVI) in catheter ablation for paroxysmal atrial fibrillation (PAF) is electrical reconnection of the PV. EFFICAS I showed correlation between contact force (CF) parameters and PV durable isolation but no prospective evaluation was made. EFFICAS II was a multicentre study to prospectively assess the impact of CF guidance for an effective reduction of PVI gaps. METHODS AND RESULTS: Pulmonary vein isolation using a radiofrequency (RF) ablation catheter with an integrated force sensor (TactiCath™) was performed in patients with PAF. Operators were provided EFFICAS I-based CF guidelines [target 20 g, range 10-30 g, minimum 400 g s force-time integral (FTI)]. Conduction gaps were assessed by remapping of PVs after 3 months, and gap rate was compared with EFFICAS I outcome. At follow up, 24 patients had 85% of PVs remaining isolated, compared with 72% in EFFICAS I (P = 0.037) in which CF guidelines were not used. The remaining 15% of gaps correlated to the number of catheter moves at creating the PVI line, quantified as Continuity Index. For PV lines with contiguous lesions and low catheter moves, durable isolation was 81% in EFFICAS I and 98% in EFFICAS II (P = 0.005). At index procedure, the number of lesions was reduced by 15% in EFFICAS II vs. EFFICAS I. CONCLUSION: The use of CF with the above guidelines and contiguous deployment of RF lesions in EFFICAS II study resulted in more durable PVI in catheter ablation of PAF.

Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size.

BACKGROUND: Electrode-tissue contact force (CF) is believed to be a major factor in radiofrequency lesion size. The purpose of this study was to determine, in the beating canine heart, the relationship between CF and radiofrequency lesion size and the accuracy of predicting CF and lesion size by measuring electrogram amplitude, impedance, and electrode temperature. METHODS AND RESULTS: Eight dogs were studied closed chest. Using a 7F catheter with a 3.5 mm irrigated electrode and CF sensor (TactiCath, St. Jude Medical), radiofrequency applications were delivered to 3 separate sites in the right ventricle (30 W, 60 seconds, 17 mL/min irrigation) and 3 sites in the left ventricle (40 W, 60 seconds, 30 mL/min irrigation) at (1) low CF (median 8 g); (2) moderate CF (median 21 g); and (3) high CF (median 60 g). Dogs were euthanized and lesion size was measured. At constant radiofrequency and time, lesion size increased significantly with increasing CF (P<0.01). The incidence of a steam pop increased with both increasing CF and higher power. Peak electrode temperature correlated poorly with lesion size. The decrease in impedance during the radiofrequency application correlated well with lesion size for lesions in the left ventricle but less well for lesions in the right ventricle. There was a poor relationship between CF and the amplitude of the bipolar or unipolar ventricular electrogram, unipolar injury current, and impedance. CONCLUSIONS: Radiofrequencylesion size and the incidence of steam pop increase strikingly with increasing CF. Electrogram parameters and initial impedance are poor predictors of CF for radiofrequency ablation.

Quantitative magnetic resonance imaging analysis of the relationship between contact force and left atrial scar formation after catheter ablation of atrial fibrillation.

BACKGROUND: Catheter contact force (CF) is an important determinant of radiofrequency (RF) lesion quality during pulmonary vein isolation (PVI). Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows good visualization of ablation lesions. OBJECTIVE: This study describes a new technique to examine the relationship between CF during RF delivery and LGE signal intensity (SI) following PVI. METHODS: Six patients underwent PVI for paroxysmal AF using a CF-sensing catheter and following preprocedural MRI. During ablation, CF-time integral (FTI) and position was documented for each RF application. All patients underwent repeat LGE MRI 3 months later. The LGE SIs were projected onto a MRI-derived 3-dimensional left atrial (LA) shell and a CF map was generated on the same shell. The entire LA surface was divided into 5 mm(2) segments. Force and LGE maps were fused and compared for each 5 mm(2) zone. An effective lesion was defined when MRI-defined scar occupied >90% of a 5 mm(2) analysis zone. RESULTS: Acute PVI was achieved in 100%. Two hundred sixty-eight RF lesions were tagged on the LA shells and given a lesion-specific FTI. Increasing FTI correlated with increased LGE SI, which was greater when the FTI was > 1,200 gs. Below an FTI of 1,200 gs, an increment in the FTI resulted in only a small increment in scar, whereas above 1,200 gs an increment in the FTI resulted in a large change of scar. CONCLUSION: There is a correlation between FTI and LGE SI in MRI following AF ablation. Real-time FTI maps are feasible and may prevent inadequate lesion formation.

Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study.

BACKGROUND: Pulmonary vein isolation is the most prevalent approach for catheter ablation of paroxysmal atrial fibrillation. Long-term success of the procedure is diminished by arrhythmia recurrences occurring predominantly because of reconnections in previously isolated pulmonary veins. The aim of the EFFICAS I multicenter study was to demonstrate the correlation between contact force (CF) parameters during initial procedure and the incidence of isolation gaps (gap) at 3-month follow-up. METHOD AND RESULTS: A radiofrequency ablation catheter with integrated CF sensor (TactiCath, Endosense, Geneva, Switzerland) was used to perform pulmonary vein isolation in 46 patients with paroxysmal atrial fibrillation. During the ablation procedure, the operator was blinded to CF information. At follow-up, an interventional diagnostic procedure was performed to assess gap location as correlated to index procedure ablation parameters. At follow-up, 65% (26/40) of patients showed ≥1 gaps. Ablations with minimum Force-Time Integral (FTI) <400 gs showed increased likelihood for reconnection (P<0.001). Reconnection correlated strongly with minimum CF (P<0.0001) and minimum FTI (P=0.0007) at the site of gap. Gap occurrence showed a strong trend with lower average CF and average FTI. CF and FTI are generally higher on the right side, although the left anterior segment presents a unique challenge to achieve stable position with good CF. CONCLUSIONS: Minimum CF and minimum FTI values are strong predictors of gap formation. Optimal CF parameter recommendations are a target CF of 20 g and a minimum FTI of 400 gs for each new lesion.

The relationship between contact force and clinical outcome during radiofrequency catheter ablation of atrial fibrillation in the TOCCATA study.

BACKGROUND: The clinical efficacy of catheter ablation of paroxysmal atrial fibrillation (AF) remains limited by difficulty in achieving durable pulmonary vein isolation (PVI). Suboptimal catheter tip-to-tissue contact force (CF) during lesion delivery is believed to reduce clinical efficacy. OBJECTIVE: To determine the relationship between catheter CF during irrigated catheter ablation for AF and clinical recurrences during follow-up. METHODS: Thirty-two patients with paroxysmal AF underwent PVI by using a radiofrequency ablation catheter with a CF sensor integrated at its tip, and they were followed for 12 months. The relationship between the CF and clinical outcomes was determined. RESULTS: Acute PVI was achieved in 100% of the veins. Thirty-five percent (351 of 1017) of the applications were placed with an average CF of <10 g (low CF). All patients treated with an average CF of <10 g (5 of 5 patients) experienced recurrences, whereas 80% of the patients treated with an average CF of >20 g (8 of 10 patients) were free from AF recurrence at 12 months. The analysis of the average force-time integral showed that 75% of the patients treated with <500 gs were recurrent whereas only 31% of the patients treated with >1000 gs had recurrences at 12 months. CONCLUSIONS: The CF during catheter ablation for AF correlates with clinical outcome. Arrhythmia control is best achieved when ablation lesions are placed with an average CF of >20 g, and clinical failure is universally noted with an average CF of <10 g.

A novel radiofrequency ablation catheter using contact force sensing: Toccata study.

OBJECTIVES: The aim of this multicenter study was to evaluate the device- and procedure-related safety of a novel force-sensing radiofrequency (RF) ablation catheter capable of measuring the real-time contact force (CF) and to present CF data and its possible implications on patient safety. BACKGROUND: The clinical outcome of RF ablation for the treatment of cardiac arrhythmias may be affected by the CF between the catheter tip and the tissue. Insufficient CF may result in an ineffective lesion, whereas excessive CF may result in complications. METHODS: Seventy-seven patients (43 with right-sided supraventricular tachycardia [SVT] and 34 with atrial fibrillation [AF]) received percutaneous ablation with the novel studied catheter. The CF applied and safety events related to the procedure were reported. RESULTS: CF values at mapping ranged from 8 ± 8 to 60 ± 35 g and from 12 ± 10 to 39 ± 29 g in the SVT group and the LA group, respectively, showing a significant interinvestigator variability (P < .0001). High transient CFs (>100 g) were noted in 27 patients (79%) of the LA group. One device-related complication (tamponade, 3%) occurred in the AF group. CONCLUSIONS: Catheter ablation using real-time CF technology is safe for the treatment of SVT and AF. High CFs may occur during catheter manipulation and not just during ablation, suggesting that measuring CF may provide additional useful information to the operator for safe catheter manipulation. In the future, CF-sensing catheters may also increase the effectiveness of RF ablations by allowing better control of the RF lesion size.

Catheter tip force required for mechanical perforation of porcine cardiac chambers.

AIMS: Catheter manipulation during ablation procedures can produce injury and tamponade. We evaluated the mechanical forces required to perforate a porcine heart with an ablation catheter. METHODS AND RESULTS: A 7 Fr, 3.5 mm irrigated radiofrequency (RF) ablation catheter with a force sensor (FS) within its tip was used to create right atrial (RA) free wall lesions in pigs. The intact heart was removed and the FS-equipped catheter was used to mechanically perforate (without RF delivery) the free walls of both atria and ventricles: directly and through an introducer sheath to prevent catheter shaft buckling. Perforation was also performed through epicardially visible RA lesions and adjacent unablated tissue. Twenty-four RA free wall lesions were created in four pigs. One hundred and forty-four mechanical perforations were performed: 44 RA, 30 left atrial (LA), 37 right ventricular (RV), and 33 left ventricular (LV). The RA and RV perforation force (PF) was lower than through the LA and LV (P<0.0001). The LV perforation time was shorter when the catheter was gripped through an introducer sheath (0.8±0.5 vs. 3.2±3 s, P<0.0001). Perforation force through transmural RA lesions was lower than through unablated RA tissue (172.4±79.1 vs. 300.6±116.8 g, P<0.0002). CONCLUSION: The force threshold for mechanical perforation in the porcine heart is lower for right- compared with left-sided chambers, and also lower through recently created RA RF lesions compared with unablated RA tissue. Left ventricular perforation is achieved more rapidly with the ablation catheter in a sheath despite the same PF because the sheath prevents catheter buckling.

Area under the real-time contact force curve (force-time integral) predicts radiofrequency lesion size in an in vitro contractile model.

INTRODUCTION: Electrode tissue contact, radiofrequency (RF) power and duration are major determinants of RF lesion size. Since contact forces (CF) vary in the beating heart, we evaluated contact force-time integral (FTI) as a predictor of lesion size at constant RF power in a contractile bench model simulating the beating heart. METHODS AND RESULTS: An open-tip irrigated catheter was attached to a movable mount incorporating a dynamic force sensor allowing closed loop control to achieve desired force variations between the catheter tip and bovine skeletal muscle placed on a ground plate. RF energy (20 and 40 W for 60 seconds, 17 cc/min irrigation) was delivered during (1) constant contact (C) at 20 g, (2) variable contact (V) with a 20 g peak and 10 g nadir, and (3) intermittent contact (I) with a 20 g peak and 0 g nadir with loss of contact. V and I protocols were performed at 50 and 100 catheter movements/min and 2 systole:diastole time ratios (50:50 and 30:70). The area under the CF curve was calculated as the FTI. Measured FTI was highest in C, intermediate during V and lowest during I and correlated linearly with lesion volume (P < 0.0001 for 20 and 40 W). Lesion volume was highest in group C, intermediate in V and lowest in group I (P < 0.05 for C vs V, V vs I, and C vs I). CONCLUSIONS: Lesion size correlates linearly with measured contact FTI. Constant contact produces the largest and intermittent contact the smallest lesions despite constant RF power and identical peak contact forces.

Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter.

INTRODUCTION: Ablation electrode-tissue contact has been shown to be an important determinant of lesion size and safety during nonirrigated ablation but little data are available during irrigated ablation. We aimed to determine the importance of contact force during irrigated-tip ablation. METHODS AND RESULTS: Freshly excised hearts from 11 male pigs were perfused and superfused using fresh, heparinized, oxygenated swine blood in an ex vivo model. One-minute ablations were placed using one of 3 different power control strategies (impedance control-15 Omega target impedance drop, and 20 W or 30 W fixed power) and 3 different contact forces (2 g, 20 g, and 60 g) to give a grid of 9 ablation groups. The force sensing catheter (Tacticath, Endosense SA) was irrigated at 17 mL/min for all of the ablations. Of a total 101 ablations, no thrombus formation was noted but popping was seen in 17 lesions. The lesion depth and incidence of pops was 5.0 +/- 1.3 mm /0%, 5.0 +/- 1.6 mm /10% and 6.7 +/- 2.5 mm /45% for the 15 Omega, 20 W, and 30 W groups (P < 0.01), respectively, and 4.4 +/- 1.8 mm /3%, 5.8 +/- 1.6 mm /17% and 6.6 +/- 2.0 mm /37% for the 2 g, 20 g, and 60 g groups, respectively (P < 0.01). The impedance drop in the first 5 seconds was significantly correlated to catheter contact force: 9.7 +/- 9.9 Omega, 22.3 +/- 11.0 Omega, and 41.7 +/- 22.1 Omega, respectively, for the 2 g, 20 g, and 60 g groups (Pearson's r = 0.65, P < 0.01). CONCLUSION: Catheter contact force has an important impact on both ablation lesion size and the incidence of pops.

Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus.

BACKGROUND: An open-irrigated radiofrequency (RF) ablation catheter was developed to measure contact force (CF). Three optical fibers measure microdeformation of the catheter tip. The purpose of this study was to (1) validate the accuracy of CF sensor (CFS) (bench test); and (2) determine the relationship between CF and tissue temperatures, lesion size, steam pop, and thrombus during RF ablation using a canine thigh muscle preparation. METHODS AND RESULTS: CFS measurements (total 1409) from 2 catheters in 3 angles (perpendicular, parallel, and 45 degrees ) were compared with a certified balance (range, 0 to 50 g). CFS measurements correlated highly (R(2) > or =0.988; mean error, < or =1.0 g). In 10 anesthetized dogs, a skin cradle over the thigh muscle was superfused with heparinized blood at 37 degrees C. A 7F catheter with 3.5-mm saline-irrigated electrode and CFS (Endosense) was held perpendicular to the muscle at CF of 2, 10, 20, 30, and 40 g. RF was delivered (n=100) for 60 seconds at 30 or 50 W (irrigation 17 or 30 mL/min). Tissue temperature (3 and 7 mm depths), lesion size, thrombus, and steam pop increased significantly with increasing CF at each RF power. Lesion size was greater with applications of lower power (30 W) and greater CF (30 to 40 g) than at high power (50 W) with lower CF (2 to 10 g). CONCLUSIONS: This novel ablation catheter, which accurately measures CF, confirmed CF is a major determinant of RF lesion size. Steam pop and thrombus incidence also increases with CF. CFS in an open-irrigated ablation catheter that may optimize the selection of RF power and application time to maximize lesion formation and reduce the risk of steam pop and thrombus.

Development and construct validation of performance metrics for multivessel coronary interventions on the VIST virtual reality simulator at PCR2005.

BACKGROUND: The first aim of this study was the development of performance metrics in a virtual reality simulation for interventional procedure in a real case of multivessel coronary disease. A second aim was to assess the construct validity of these metrics by comparing the performance of interventional cardiologists with different levels of experience. METHODS: Ninety-four practicing interventional cardiologists attending the EuroPCR 2005 in Paris, France participated in this study. Complete data was available on eighty-nine participants (95%). Participants were divided into three categories depending on experience. Group 1 (novices): N = 33, < 1 years experience; Group 2 (intermediate experience): N = 14, >50 cases per year for the last two years and Group 3 (master physicians): N = 42 participants completed > 100 cases per year during the last five years. PROCEDURE: Over a period of months during 2004-2005 we identified potential performance metrics for cases of coronary artery disease which were then applied to a case of a patient admitted because of stable angina (class 1) with multivessel coronary disease. Patient's coronary anatomy and lesions were then reconstructed and implemented for the VIST virtual reality simulator. All participants were required to perform this case. RESULTS: Overall, experienced interventional cardiologists performed significantly better than the novices for traditional metrics such as time (p = 0.03), contrast fluid (p = 0.0008) and Fluroscopy time (p = 0.005). Master physicians performed significantly better than the other two groups on metrics which assessed technical performance e.g., time to ascend the aorta (p = 0.0004) and stent placement accuracy (p = 0.02). Furthermore, master physicians made fewer handling errors than the intermediated group who in turn made fewer than the novice group (p = 0.0003). Performance consistency was also a linear function of experience. CONCLUSIONS: Novel performance metrics developed for the assessment of technical skills for a simulated intervention for multi-vessel coronary disease showed that more experienced interventional cardiologists performed the procedure better than less experienced interventionalists thus demonstrating construct validity of the metrics.