Activating effective functional hand movements in individuals with complete tetraplegia through neural stimulation.

Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw.

Restoring Hand Functions in People with Tetraplegia through Multi-Contact, Fascicular, and Auto-Pilot Stimulation: A Proof-of-Concept Demonstration.

Two multi-contact epineural electrodes were placed around radial and median nerves of two subjects with high tetraplegia C4, American Spinal Injury Association Impairment Scale (AIS) A, group 0 of the International Classification for Surgery of the Hand in Tetraplegia. The purpose was to study the safety and capability of these electrodes to generate synergistic motor activation and functional movements and to test control interfaces that allow subjects to trigger pre-programmed stimulation sequences. The device consists of a pair of neural cuff electrodes and percutaneous cables with two extracorporeal connection cables inserted during a surgical procedure and maintained for 28 days. Continuity tests of the electrodes, selectivity of movements induced, motor capacities for grasping and gripping, conformity of the control order, tolerance, and acceptability were assessed. Neither of the two participants showed general and local comorbidity. Acceptability was optimal. None of the stimulation configurations generated contradictory movements. The success rate in task execution by the electro-stimulated hand exceeded the target of 50% (54% and 51% for patients 1 and 2, respectively). The compliance rate of the control orders in both patients was >90% using motion inertial measurement unit (IMU)-based detection and 100% using electromyography (EMG)-based detection in patient 1. These results support the relevance of neural stimulation of the tetraplegic upper limb with a more selective approach, using multi-contact epineural electrodes with nine and six contact points for the median and radial nerve respectively.

In Vivo Sustained Release of Peptide Vaccine Mediated by Dendritic Mesoporous Silica Nanocarriers.

Mesoporous silica nanoparticles have drawn increasing attention as promising candidates in vaccine delivery. Previous studies evaluating silica-based vaccine delivery systems concentrated largely on macromolecular antigens, such as inactivated whole viruses. In this study, we synthesized dendritic mesoporous silica nanoparticles (DMSNs), and we evaluated their effectiveness as delivery platforms for peptide-based subunit vaccines. We encapsulated and tested in vivo an earlier reported foot-and-mouth disease virus (FMDV) peptide vaccine (B2T). The B2T@DMSNs formulation contained the peptide vaccine and the DMSNs without further need of other compounds neither adjuvants nor emulsions. We measured in vitro a sustained release up to 930 h. B2T@DMSNs-57 and B2T@DMSNs-156 released 23.7% (135 µg) and 22.8% (132 µg) of the total B2T. The formation of a corona of serum proteins around the DMSNs increased the B2T release up to 61% (348 µg/mg) and 80% (464 µg/mg) for B2T@DMSNs-57 and B2T@DMSNs-156. In vitro results point out to a longer sustained release, assisted by the formation of a protein corona around DMSNs, compared to the reference formulation (i.e., B2T emulsified in Montanide). We further confirmed in vivo immunogenicity of B2T@DMSNs in a particle size-dependent manner. Since B2T@DMSNs elicited specific immune responses in mice with high IgG production like the reference B2T@Montanide™, self-adjuvant properties of the DMSNs could be ascribed. Our results display DMSNs as efficacious nanocarriers for peptide-based vaccine administration.

Differences in scar lesion formation between radiofrequency and cryoballoon in atrial fibrillation ablation: a comparison study using ultra-high-density mapping.

AIMS: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is usually associated to conduction gaps in pulmonary veins (PVs). Our objective was to characterize gaps in patients with recurrences after a first radiofrequency (RF) or cryoballoon (CB) PVI procedure, using a high-density mapping (HDM) system. METHODS AND RESULTS: Fifty patients with AF recurrence after a first PVI procedure (pre-RF 25 patients; pre-CB 25 patients) were included at two centres. Activation map (AM) and voltage map (VM) of the left atrium and PVs were built using the HDM Rhythmia® system. Superior PVs were reconnected more frequently in both groups. Right PVs were reconnected more frequently in pre-RF patients. Pre-RF patients had more reconnected veins than pre-CB patients (mean ± standard deviation: 3.00 ± 0.96 vs. 1.88 ± 1.13; P < 0.001) and more gaps (4.84 ± 2.06 vs. 2.16 ± 1.49; P < 0.001). Gaps in the VM were wider in pre-CB patients (16.5 ± 9.5 mm vs. 12.1 ± 4.8 mm; P = 0.006). There was a gap in 179 of the 800 PV segments analysed (22%); 52% were identified in both AM and VM maps; 39% only in the AM and 8% only in the VM. The highest sensitivity and specificity for gap detection was obtained with VM in pre-CB patients and with AM in pre-RF patients. CONCLUSION: In conclusion, HDM seems to be a useful and precise tool to detect conduction gaps after a first PVI procedure. The anatomical pattern and location of gaps depends on the technique used previously, usually being multiple, smaller, and better detected by AM after RF, and fewer, wider, and better detected by VM after CB.

Real-Time Closed-Loop Functional Electrical Stimulation Control of Muscle Activation with Evoked Electromyography Feedback for Spinal Cord Injured Patients.

Functional electrical stimulation (FES) is a neuroprosthetic technique to help restore motor function of spinal cord-injured (SCI) patients. Through delivery of electrical pulses to muscles of motor-impaired subjects, FES is able to artificially induce their muscle contractions. Evoked electromyography (eEMG) is used to record such FES-induced electrical muscle activity and presents a form of [Formula: see text]-wave. In order to monitor electrical muscle activity under stimulation and ensure safe stimulation configurations, closed-loop FES control with eEMG feedback is needed to be developed for SCI patients who lose their voluntary muscle contraction ability. This work proposes a closed-loop FES system for real-time control of muscle activation on the triceps surae and tibialis muscle groups through online modulating pulse width (PW) of electrical stimulus. Subject-specific time-variant muscle responses under FES are explicitly reflected by muscle excitation model, which is described by Hammerstein system with its input and output being, respectively, PW and eEMG. Model predictive control is adopted to compute the PW based on muscle excitation model which can online update its parameters. Four muscle activation patterns are provided as desired control references to validate the proposed closed-loop FES control paradigm. Real-time experimental results on three able-bodied subjects and five SCI patients in clinical environment show promising performances of tracking the aforementioned reference muscle activation patterns based on the proposed closed-loop FES control scheme.

Elucidation of hidden slow conduction by double ventricular extrastimuli: a method for further arrhythmic substrate identification in ventricular tachycardia ablation procedures.

Aims: Identification of local abnormal electrograms (EGMs) during ventricular tachycardia substrate ablation (VTSA) is challenging when they are hidden within the far-field signal. This study analyses whether the response to a double ventricular extrastimulus during substrate mapping could identify slow conducting areas that are hidden during sinus rhythm. Methods and results: Consecutive patients (n = 37) undergoing VTSA were prospectively included. Bipolar EGMs with >3 deflections and duration <133 ms were considered as potential hidden slow conduction EGMs (HSC-EGM) if located within/surrounding the scar area. Whenever a potential HSC-EGM was identified, a double ventricular extrastimulus was delivered. If the local potential delayed, it was annotated as HSC-EGM. The incidence of HSC-EGM in core, border-zone, and normal-voltage regions was determined. Ablation was delivered at conducting channel entrances and HSC-EGMs. VT inducibility after VTSA obtained was compared with data from a historic control group. 2417 EGMs were analyzed. 575 (23.7%) qualified as potential HSC-EGM, and 198 of them were tagged as HSC-EGMs. Scars in patients with HSC-EGMs (n = 21, 56.7%) were smaller (35.424.7 vs 67.639.1 cm2; P = 0.006) and more heterogeneous (core/scar area ratio 0.250.2 vs 0.450.19; P = 0.02). 28.8% of HSC-EGMs were located in normal-voltage tissue; 81.3% were targeted for ablation. Patients undergoing VTSA incorporating HSC analysis needed less radiofrequency time (17.411 vs 2310.7 minutes; P = 0.016) and had a lower rate of VT inducibility after VTSA than the historic controls (24.3% vs 50%; P = 0.018). Conclusion: Ventricular tachycardia substrate ablation incorporating HSC analysis allowed further arrhythmic substrate identification (especially in normal-voltage areas) and reduced RF time and VT inducibility after VTSA.

Multielectrode vs. point-by-point mapping for ventricular tachycardia substrate ablation: a randomized study.

Aims: Ventricular tachycardia (VT) substrate ablation is based on detailed electroanatomical maps (EAM). This study analyses whether high-density multielectrode mapping (MEM) is superior to conventional point-by-point mapping (PPM) in guiding VT substrate ablation procedures. Methods and results: This was a randomized controlled study (NCT02083016). Twenty consecutive ischemic patients undergoing VT substrate ablation were randomized to either group A [n = 10; substrate mapping performed first by PPM (Navistar) and secondly by MEM (PentaRay) ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM ablation guided by MEM]. Ablation was performed according to the scar-dechanneling technique. Late potential (LP) pairs were defined as a Navistar-LP and a PentaRay-LP located within a three-dimensional distance of ≤ 3 mm. Data obtained from EAM, procedure time, radiofrequency time, and post-ablation VT inducibility were compared between groups. Larger bipolar scar areas were obtained with MEM (55.7±31.7 vs. 50.5±26.6 cm2; P = 0.017). Substrate mapping time was similar with MEM (19.7±7.9 minutes) and PPM (25±9.2 minutes); P = 0.222. No differences were observed in the number of LPs identified within the scar by MEM vs. PPM (73±50 vs. 76±52 LPs per patient, respectively; P = 0.965). A total of 1104 LP pairs were analysed. Using PentaRay, far-field/LP ratio was significantly lower (0.58±0.4 vs. 1.64±1.1; P = 0.01) and radiofrequency time was shorter [median (interquartile range) 12 (7-20) vs. 22 (17-33) minutes; P = 0.023]. No differences were observed in VT inducibility after procedure. Conclusion: MEM with PentaRay catheter provided better discrimination of LPs due to a lower sensitivity for far-field signals. Ablation guided by MEM was associated with a shorter radiofrequency time.

Effects of Sensitive Electrical Stimulation-Based Somatosensory Cueing in Parkinson's Disease Gait and Freezing of Gait Assessment.

This study aims to investigate the effect of a somatosensory cueing on gait disorders in subjects with Parkinson's disease (PD). After having performed stepping in place and timed up and go assessing tasks, 13 participants with PD were equipped with an electrical stimulator and an inertial measurement unit (IMU) located under the lateral malleolus on the sagittal plane. Electrodes were positioned under the arch of the foot and electrical stimulation (ES) parameters (five 500 µs/phase charge-balanced biphasic pulses delivered at 200 Hz, repeated four times at 10 Hz) adjusted to deliver a sensitive signal. Online IMU signal was processed in order to trigger ES at heel off detection. Starting from a quiet standing posture, subjects were asked to walk at their preferred speed on a path including 5 m straight line, u-turn, and walk around tasks. Three situations were considered: no stimulation baseline precondition (C0), ES condition (C1), and no stimulation baseline post-condition (C0bis), for eliminating a learning effect possibility. In ES condition (C1) the time to execute the different tasks was globally decreased in all the subjects (n = 13). Participants' results were then grouped regarding whether they experienced freezing of gait (FOG) or not during C0 no stimulation baseline precondition. In "freezer" subjects (n = 9), the time to complete the entire path was reduced by 19%. FOG episodes occurrence was decreased by 12% compared to baseline conditions. This preliminary work showed a positive global effect on gait and FOG in PD by a somatosensory cueing based on sensitive electrical stimulation.

Cardiac magnetic resonance-aided scar dechanneling: Influence on acute and long-term outcomes.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) provides tissue characterization of ventricular myocardium and scar that can be depicted as pixel signal intensity (PSI) maps. OBJECTIVE: To assess the possible benefit of guiding the ventricular tachycardia (VT) substrate mapping by integrating these PSI maps into the navigation system. METHODS: In total, 159 consecutive patients (66 ± 11 years old, 151 men [95%]) with scar-related left ventricular (LV) VT were included. VT substrate ablation used the scar dechanneling technique. A CMR-aided ablation using the PSI maps was performed in 54 patients (34%). Procedural data as well as acute and long-term outcomes were compared with those of the remaining 105 patients (66%). RESULTS: Mean procedure duration and fluoroscopy time were 229 ± 67 minutes and 20 ± 9 minutes, respectively, without significant differences between groups. Both the number of radiofrequency (RF) applications and RF delivery time were lower in the CMR-aided group (28 ± 18 applications vs 36 ± 18 applications, P = .037, and 19 ± 12 minutes vs 27 ± 16 minutes, P = .009, respectively). After substrate ablation, monomorphic VT inducibility was lower in the CMR-aided than in the control group (17 [32%] vs 53 [51%] patients, P = .022). After a mean follow-up period of 20 ± 19 months, patients from the CMR-aided group had a lower recurrence rate than those in the control group (10 patients [18.5%] vs 46 patients [43.8%], respectively, P = .002; log-rank P = .017). Multivariate analysis found that CMR-aided ablation (hazard ratio, 0.48 [95% Confirdence Interval (CI) 0.24-0.96], P = .037) was an independent predictor of recurrences. CONCLUSION: CMR-aided scar dechanneling is associated with a lower need for RF delivery, higher noninducibility rates after substrate ablation, and a higher VT-recurrence-free survival.

Left atrial fibrosis quantification by late gadolinium-enhanced magnetic resonance: a new method to standardize the thresholds for reproducibility.

AIMS: Identification of left atrial (LA) fibrosis through late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) remains controversial due to the heterogeneity and lack of reproducibility of proposed methods. Our aim is to describe a normalized, reproducible, standardized method to evaluate LA fibrosis through LGE-CMR. METHODS AND RESULTS: Electrocardiogram- and respiratory-gated 3-Tesla LGE-CMR was performed in 10 healthy young volunteers and 30 patients with atrial fibrillation (AF): 10 with paroxysmal AF, 10 with persistent AF, and 10 with a previous AF ablation procedure. Local image intensity ratio (IIR) of the LA was calculated as the absolute pixel intensity to mean blood pool intensity ratio. The healthy atrial tissue threshold was defined in young healthy volunteers (upper limit of normality set at IIR tissue mean plus 2 SDs). Dense atrial scarring was characterized in patients with previous radiofrequency-induced scarring (post-AF ablation patients). Validation groups consisted of patients with paroxysmal and persistent AFs. The upper limit of normal IIR was 1.20; IIR values higher than 1.32 (60% of mean maximum pixel intensity in post-ablation patients) were considered dense scar. Image intensity ratio values between 1.2 and 1.32 identified interstitial fibrosis. Patients with paroxysmal and persistent AFs had less atrial fibrotic tissue compared with post-ablation patients. Endocardial bipolar voltage was correlated to IIR values. CONCLUSIONS: An IIR of 1.2 identifies the upper limit of normality in healthy young individuals. An IIR of >1.32 defines dense atrial fibrosis in post-ablation patients. Our results provide a consistent, comparable, and normalized tool to assess atrial arrhythmogenic substrate.

Real-time estimation of FES-induced joint torque with evoked EMG : Application to spinal cord injured patients.

BACKGROUND: Functional electrical stimulation (FES) is a neuroprosthetic technique for restoring lost motor function of spinal cord injured (SCI) patients and motor-impaired subjects by delivering short electrical pulses to their paralyzed muscles or motor nerves. FES induces action potentials respectively on muscles or nerves so that muscle activity can be characterized by the synchronous recruitment of motor units with its compound electromyography (EMG) signal is called M-wave. The recorded evoked EMG (eEMG) can be employed to predict the resultant joint torque, and modeling of FES-induced joint torque based on eEMG is an essential step to provide necessary prediction of the expected muscle response before achieving accurate joint torque control by FES. METHODS: Previous works on FES-induced torque tracking issues were mainly based on offline analysis. However, toward personalized clinical rehabilitation applications, real-time FES systems are essentially required considering the subject-specific muscle responses against electrical stimulation. This paper proposes a wireless portable stimulator used for estimating/predicting joint torque based on real time processing of eEMG. Kalman filter and recurrent neural network (RNN) are embedded into the real-time FES system for identification and estimation. RESULTS: Prediction results on 3 able-bodied subjects and 3 SCI patients demonstrate promising performances. As estimators, both Kalman filter and RNN approaches show clinically feasible results on estimation/prediction of joint torque with eEMG signals only, moreover RNN requires less computational requirement. CONCLUSION: The proposed real-time FES system establishes a platform for estimating and assessing the mechanical output, the electromyographic recordings and associated models. It will contribute to open a new modality for personalized portable neuroprosthetic control toward consolidated personal healthcare for motor-impaired patients.

Approach to ablation of unmappable ventricular arrhythmias.

Most patients with structural heart disease referred for ventricular tachycardia ablation have unstable tachycardias not suitable for conventional mapping (ie, entrainment mapping). Substrate-guided mapping and ablation during sinus rhythm are intended to overcome the limitations of conventional mapping and ablation. Substrate ablation permits elimination of multiple ventricular tachycardias irrespective of their inducibility during the procedure or their hemodynamic tolerability. Moreover, the elimination/isolation of the arrhythmogenic substrate identified during sinus rhythm has been associated with better outcomes. There is currently no standardized approach for substrate-guided ablation. This article discusses the main aspects of the proposed techniques and substrate ablation targets.

Scar dechanneling: new method for scar-related left ventricular tachycardia substrate ablation.

BACKGROUND: Ventricular tachycardia (VT) substrate ablation usually requires extensive ablation. Scar dechanneling technique may limit the extent of ablation needed. METHODS AND RESULTS: The study included 101 consecutive patients with left ventricular scar-related VT (75 ischemic patients; left ventricular ejection fraction, 36 ± 13%). Procedural end point was the elimination of all identified conducting channels (CCs) by ablation at the CC entrance followed by abolition of residual inducible VTs. By itself, scar dechanneling rendered noninducibility in 54.5% of patients; ablation of residual inducible VT increased noninducibility to 78.2%. Patients needing only scar dechanneling had a shorter procedure (213 ± 64 versus 244 ± 71 minutes; P = 0.027), fewer radiofrequency applications (19 ± 11% versus 27 ± 18%; P = 0.01), and external cardioversion/defibrillation shocks (20% versus 65.2%; P < 0.001). At 2 years, patients needing scar dechanneling alone had better event-free survival (80% versus 62%) and lower mortality (5% versus 11%). Incomplete CC-electrogram elimination was the only independent predictor (hazard ratio, 2.54 [1.06-6.10]) for the primary end point. Higher end point-free survival rates were observed in patients noninducible after scar dechanneling (log-rank P = 0.013) and those with complete CC-electrogram elimination (log-rank P = 0.013). The complications rate was 6.9%, with no deaths. CONCLUSIONS: Scar dechanneling alone results in low recurrence and mortality rates in more than half of patients despite the limited ablation extent required. Residual inducible VT ablation improves acute results, but patients who require it have worse outcomes. Recurrences are mainly related to incomplete CC-electrogram elimination.

Impact of earliest activation site location in the septal right ventricular outflow tract for identification of left vs right outflow tract origin of idiopathic ventricular arrhythmias.

BACKGROUND: The earliest activation site (EAS) location in the septal right ventricular outflow tract (RVOT) could be an additional mapping data predictor of left ventricular outflow tract (LVOT) vs RVOT origin of idiopathic ventricular arrhythmias (VAs). OBJECTIVE: The purpose of this study was to assess the impact of EAS location in predicting LVOT vs RVOT origin. METHODS: Macroscopic and histologic study was performed in 12 postmortem hearts. Electroanatomic maps (EAMs) from 37 patients with outflow tract (OT) VA with the EAS in the septal RVOT were analyzed. Pulmonary valve (PV) was defined by voltage scanning after validation of voltage thresholds by image integration. EAM measurements were correlated with those of macroscopic/histologic study. RESULTS: A cutoff value of 1.9 mV discriminated between subvalvular and supravalvular positions (90% sensitivity, 96% specificity). EAS ≥1 cm below PV excluded RVOT site of origin (SOO). According to anatomic findings (distance PV-left coronary cusp = 5 ± 3 vs PV-right coronary cusp = 11 ± 5 mm), EAS-PV distance was significantly shorter in VAs arising from left coronary cusp than from the other LVOT locations (4.2 ± 5.4 mm vs 9.2 ± 7 mm; P = .034). The 10-ms isochronal longitudinal/perpendicular diameter ratio was higher in the RVOT vs the LVOT SOO group (1.97 ± 1.2 vs 0.79 ± 0.49; P = .001). An algorithm based on EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio predicted LVOT SOO with 91% sensitivity and 100% specificity. CONCLUSION: An algorithm based on the EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio accurately predicts LVOT vs RVOT SOO in outflow tract VAs with EAS in the septal RVOT.

Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation.

AIMS: The endocardial vs. epicardial origin of ventricular arrhythmia (VA) can be inferred from detailed electrocardiogram (ECG) analysis. However, despite its clinical usefulness, ECG has limitations. Alternatively, scarred tissue sustaining VAs can be identified by contrast-enhanced cardiac magnetic resonance (ce-CMR). The objective of this study was to determine the clinical value of analysing the presence and distribution pattern of scarred tissue in the ventricles to identify the VA site of origin and the ablation approach required. METHODS AND RESULTS: A ce-CMR study was carried out before the index ablation procedure in a cohort of 80 patients with non-idiopathic VA. Hyper-enhancement (HE) in each ventricular segment was coded as absent, subendocardial, transmural, mid-myocardial, or epicardial. The endocardial or epicardial VA site of origin was also assigned according to the approach needed for ablation. The clinical VA was successfully ablated in 77 (96.3%) patients, all of them showing HE on ce-CMR. In segments with successful ablation of the clinical ventricular tachycardia, HE was absent in 3 (3.9%) patients, subendocardial in 19 (24.7%), transmural in 36 (46.7%), mid-myocardial in 8 (10.4%), and subepicardial in 11 (14.3%) patients. Epicardial ablation of the index VA was necessary in 3 (6.1%) ischaemic and 12 (42.9%) non-ischaemic patients. The presence of subepicardial HE in the successful ablation segment had 84.6% sensitivity and 100% specificity in predicting an epicardial origin of the VA. CONCLUSION: Contrast-enhanced cardiac magnetic resonance is helpful to localize the target ablation substrate of non-idiopathic VA and also to plan the approach needed, especially in non-ischaemic patients.

Transthoracic epicardial ablation of mitral isthmus for treatment of recurrent perimitral flutter.

BACKGROUND: Perimitral flutter (PMF) is a common form of left atrial tachycardia after atrial fibrillation (AF) ablation. The mitral isthmus (MI) is the standard ablation target. However, in some cases bidirectional block cannot be achieved. OBJECTIVE: The purpose of this study was to describe the first experience using a transthoracic epicardial (TTE) approach to treat recurrent PMF after prior unsuccessful ablation. METHODS: This is a case series of four patients with recurrence of highly symptomatic drug-refractory PMF (all male, median age 55 years, 3/4 hypertensive, 2/4 persistent AF, median AF period 24 months). Three patients presented with PMF-related tachymyocardiopathy. TTE ablation of MI was performed after a median of two prior endocardial MI and coronary sinus ablation attempts, using an open-tip 3.5-mm irrigated catheter (40 W, 45ºC). Persistent bidirectional block was assessed by activation mapping and differential pacing and was achieved in all patients. RESULTS: No PMF recurrence was observed after median follow-up of 18 months (range 15-22 months; two patients without antiarrhythmic drugs and two with previously ineffective amiodarone). Left ventricular function normalized in all three patients with tachycardiomyopathy. There were no complications related to TTE approach. CONCLUSION: The present study is the first to report the feasibility of a TTE approach for highly symptomatic PMF refractory to endocardial and coronary sinus MI ablation.

Alterations of the erythrocyte membrane proteome and cytoskeleton network during storage--a possible tool to identify autologous blood transfusion.

Mature red blood cells (RBCs) are the end-stage of a development process that starts in the bone marrow and continues to differentiate, through reticulocyte stage, entering into the circulation with a four-month lifespan. While stored, RBCs undergo different changes. The aim of this study was to evaluate changes occurring in RBC membranes during storage that could be used as possible markers to detect the misuse of blood transfusion in sports. Whole blood was collected from two volunteers in blood bags and stored for 42 days at 4°C. At different times (1, 7, 21, and 42 days of storage) whole blood was extracted under sterile conditions and submitted to RBC membrane ghost preparation and further analysis. Proteomic methods were applied using two strategies: protein oriented using 2-DE gels and peptide oriented using isobaric tags for relative and absolute quantitation (iTRAQ). In both approaches, the goal was to compare detectable changes in RBC membrane proteome before and after standard storage at different times. Some of the changes were confirmed with both methodologies employed, while with others only with one of them. Complementarities of the methods in this case showed to be an advantage. Changes were observed in two different protein complexes. In one of them, changes consisted of proteins decreasing, while increasing in the other during storage of RBCs. They are mostly located in cytoskeleton--spectrin ß, band 4.2, ankyrin-1, tropomodulin-1, ß adducin, band 4.9 (dematin), tropomyosin, while some changes were also observed in transmembrane proteins (glycophorin C, aquaporin-1, band 3).

Displacement of the target ablation site and ventricles during premature ventricular contractions: relevance for radiofrequency catheter ablation.

BACKGROUND: During premature ventricular contractions (PVCs), a spatial displacement of the ventricles and the target ablation site with respect to the sinus rhythm (SR) position is observed during mapping and ablation. OBJECTIVES: To analyze this displacement and its relevance for image integration and PVC ablation. METHODS: The electroanatomical activation maps (EAMs) of 55 consecutive patients who underwent PVC ablation were analyzed. Spatial displacement between each point position during PVC and SR was obtained. RESULTS: A total of 6923 points from 71 EAMs were analyzed. Overall, the median distance between the point position during SR and PVC for all the points was 9.42 mm (interquartile range [IQR]: 6.19-12.85). The EAM points from the right ventricle showed more displacement than did those from the left ventricle: 10.35 mm (IQR: 7.16-13.95) vs 7.62 mm (IQR: 5.20-10.81); P <.001. The ventricular end-diastolic volume of the EAM during SR was greater than that during PVC (median difference: 9.75 [IQR: 0.37-19.67] mL; P = .002). A shorter coupling interval of the PVC was associated with greater spatial displacement (r = -.521; P <.001), higher end-diastolic volume reduction with respect to the SR beat (r = -.718; P = .001), and worse image integration (mean point-to-surface distance between EAM and 3-dimensional computed tomography-derived structure; r = -.642; P = .018). CONCLUSIONS: There is a significant spatial displacement between the point position in SR and PVC, mainly in the right ventricle. This displacement increases with the shortening of the PVC coupling interval and can result in poorer image fusion and difficult catheter navigation/positioning for ablation.

Combined endocardial and epicardial catheter ablation in arrhythmogenic right ventricular dysplasia incorporating scar dechanneling technique.

BACKGROUND: Ventricular tachycardia (VT) ablation in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has a low success rate. A more extensive epicardial (Epi) arrhythmogenic substrate could explain the low efficacy. We report the results of combined endocardial (Endo) and Epi VT ablation and conducting channel (CC) elimination. METHODS AND RESULTS: Eleven consecutive patients with ARVD/C were included in the study. A high-density 3D Endo (321±93 sites mapped) and Epi (302±158 sites mapped) electroanatomical voltage map was obtained during sinus rhythm to define scar areas (<1.5 mV) and CCs inside the scars, between scars, or between the tricuspid annulus and a scar. The end point of the ablation procedure was the elimination of all identified CCs (scar dechanneling) and the abolition of all inducible VTs. The mean procedure and fluoroscopy time were 177±63 minutes and 20±8 minutes, respectively. Epi scar area was larger in all cases (26±18 versus 94±45 cm(2), P<0.01). The combined Endo and Epi VT ablation eliminated all clinical and induced VTs, and the addition of scar dechanneling resulted in noninducibility in all cases. Seven patients continued on sotalol. During a median follow-up of 11 months (6-24 months), only 1 (9%) patient had a VT recurrence. There was a single major bleeding event that did not preclude a successful procedure. CONCLUSIONS: Combined Endo and Epi mapping reveals a wider Epi VT substrate in patients with ARVD/C with clinical VTs. As a first-line therapy, combined Endo and Epi VT ablation incorporating scar dechanneling achieves a very good short- and midterm success rate.

Integration of 3D electroanatomic maps and magnetic resonance scar characterization into the navigation system to guide ventricular tachycardia ablation.

BACKGROUND: Scar heterogeneity identified with contrast-enhanced cardiac magnetic resonance (CE-CMR) has been related to its arrhythmogenic potential by using different algorithms. The purpose of the study was to identify the algorithm that best fits with the electroanatomic voltage maps (EAM) to guide ventricular tachycardia (VT) ablation. METHODS AND RESULTS: Three-dimensional scar reconstructions from preprocedural CE-CMR study at 3T were obtained and compared with EAMs of 10 ischemic patients submitted for a VT ablation. Three-dimensional scar reconstructions were created for the core (3D-CORE) and border zone (3D-BZ), applying cutoff values of 50%, 60%, and 70% of the maximum pixel signal intensity to discriminate between core and BZ. The left ventricular cavity from CE-CMR (3D-LV) was merged with the EAM, and the 3D-CORE and 3D-BZ were compared with the corresponding EAM areas defined with standard cutoff voltage values. The best match was obtained when a cutoff value of 60% of the maximum pixel signal intensity was used, both for core (r(2)=0.827; P<0.001) and BZ (r(2)=0.511; P=0.020), identifying 69% of conducting channels (CC) observed in the EAM. Matching improved when only the subendocardial half of the wall was segmented (CORE: r(2)=0.808; P<0.001 and BZ: r(2)=0.485; P=0.025), identifying 81% of CC. When comparing the location of each bipolar voltage intracardiac electrogram with respect to the 3D CE-CMR-derived structures, a Cohen κ coefficient of 0.70 was obtained. CONCLUSIONS: Scar characterization by means of high resolution CE-CMR resembles that of EAM and can be integrated into the CARTO system to guide VT ablation.