Anesthetic Management for Ventricular Tachycardia Ablation: A National Anesthesia Clinical Outcomes Registry Analysis.

OBJECTIVES: The authors analyzed anesthetic management trends during ventricular tachycardia (VT) ablation, hypothesizing that (1) monitored anesthesia care (MAC) is more commonly used than general anesthesia (GA); (2) MAC uses significantly increased after release of the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias; and (3) anesthetic approach varies based on patient and hospital characteristics. DESIGN: Retrospective study. SETTING: National Anesthesia Clinical Outcomes Registry data. PARTICIPANTS: Patients 18 years or older who underwent elective VT ablation between 2013 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Covariates were selected a priori within multivariate models, and interrupted time-series analysis was performed. Of the 15,505 patients who underwent VT ablation between 2013 and 2021, 9,790 (63.1%) received GA. After the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias supported avoidance of GA in idiopathic VT, no statistically significant increase in MAC was evident (immediate change in intercept post-consensus statement release adjusted odds ratio 1.41, p = 0.1629; change in slope post-consensus statement release adjusted odds ratio 1.06 per quarter, p = 0.1591). Multivariate analysis demonstrated that sex, American Society of Anesthesiologists physical status, age, and geographic location were statistically significantly associated with the anesthetic approach. CONCLUSIONS: GA has remained the primary anesthetic type for VT ablation despite the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias suggested its avoidance in idiopathic VT. Achieving widespread clinical practice change is an ongoing challenge in medicine, emphasizing the importance of developing effective implementation strategies to facilitate awareness of guideline release and subsequent adherence to and adoption of recommendations.

Anesthetic Choice for Cardiovascular Implantable Electronic Device Placement and Lead Removal: A National Anesthesia Clinical Outcomes Registry Analysis.

OBJECTIVE: The authors evaluated the anesthetic approach for cardiovascular implantable electronic device (CIED) placement and transvenous lead removal, hypothesizing that monitored anesthesia care is used more frequently than general anesthesia. DESIGN: A retrospective study. SETTING: National Anesthesia Clinical Outcomes Registry data. PARTICIPANTS: Adult patients who underwent CIED (permanent cardiac pacemaker or implantable cardioverter-defibrillator [ICD]) placement or transvenous lead removal between 2010 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Covariates were selected a priori within multivariate models to assess predictors of anesthetic type. A total of 87,530 patients underwent pacemaker placement, 76,140 had ICD placement, 2,568 had pacemaker transvenous lead removal, and 4,861 had ICD transvenous lead extraction; 51.2%, 45.64%, 16.82%, and 45.64% received monitored anesthesia care, respectively. A 2%, 1% (both p < 0.0001), and 2% (p = 0.0003) increase in monitored anesthesia care occurred for each 1-year increase in age for pacemaker placement, ICD placement, and pacemaker transvenous lead removal, respectively. American Society of Anesthesiologists (ASA) physical status ≤III for pacemaker placement, ASA ≥IV for ICD placement, and ASA ≤III for pacemaker transvenous lead removal were 7% (p = 0.0013), 5% (p = 0.0144), and 27% (p = 0.0247) more likely to receive monitored anesthesia care, respectively. Patients treated in the Northeast were more likely to receive monitored anesthesia care than in the West for all groups analyzed (p < 0.0024). Male patients were 24% less likely to receive monitored anesthesia care for pacemaker transvenous lead removal (p = 0.0378). For every additional 10 pacemaker or ICD lead removals performed in a year, a 2% decrease in monitored anesthesia care was evident (p = 0.0271, p < 0.0001, respectively). CONCLUSIONS: General anesthesia still has a strong presence in the anesthetic management of both CIED placement and transvenous lead removal. Anesthetic choice, however, varies with patient demographics, hospital characteristics, and geographic region.

Long-haul COVID: healthcare utilization and medical expenditures 6 months post-diagnosis.

BACKGROUND: Despite extensive evidence that COVID-19 symptoms may persist for up to a year, their long-term implications for healthcare utilization and costs 6 months post-diagnosis remain relatively unexplored. We examine patient-level association of COVID-19 diagnosis association of COVID-19 diagnosis with average monthly healthcare utilization and medical expenditures for up to 6 months, explore heterogeneity across age groups and determine for how many months post-diagnosis healthcare utilization and costs of COVID-19 patients persist above pre-diagnosis levels. METHODS: This population-based retrospective cohort study followed COVID-19 patients' healthcare utilization and costs from January 2019 through March 2021 using claims data provided by the COVID-19 Research Database. The patient population includes 250,514 individuals infected with COVID-19 during March-September 2020 and whose last recorded claim was not hospitalization with severe symptoms. We measure the monthly number and costs of total visits and by telemedicine, preventive, urgent care, emergency, immunization, cardiology, inpatient or surgical services and established patient or new patient visits. RESULTS: The mean (SD) total number of monthly visits and costs pre-diagnosis were .4783 (4.0839) and 128.06 (1182.78) dollars compared with 1.2078 (8.4962) visits and 351.67 (2473.63) dollars post-diagnosis. COVID-19 diagnosis associated with .7269 (95% CI, 0.7088 to 0.7449 visits; P < .001) more total healthcare visits and an additional $223.60 (95% CI, 218.34 to 228.85; P < .001) in monthly costs. Excess monthly utilization and costs for individuals 17 years old and under subside after 5 months to .070 visits and $2.77, persist at substantial levels for all other groups and most pronounced among individuals age 45-64 (.207 visits and $73.43) and 65 years or older (.133 visits and $60.49). CONCLUSIONS: This study found that COVID-19 diagnosis was associated with increased healthcare utilization and costs over a six-month post-diagnosis period. These findings imply a prolonged burden to the US healthcare system from medical encounters of COVID-19 patients and increased spending.

Anesthetic Choice for Atrial Fibrillation Ablation: A National Anesthesia Clinical Outcomes Registry Analysis.

OBJECTIVE: The authors evaluated the type of anesthesia administered in atrial fibrillation ablation, hypothesizing that monitored anesthesia care is used less frequently than general anesthesia. DESIGN: A retrospective study. SETTING: National Anesthesia Clinical Outcomes Registry data, which are multi-institutional from across the United States. PARTICIPANTS: Adult patients who underwent elective atrial fibrillation ablation between 2013 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: National Anesthesia Clinical Outcomes Registry data were evaluated, and covariates were selected a priori within multivariate models to assess for predictors of anesthetic type. A total of 54,321 patients underwent atrial fibrillation ablation; 3,251 (6.0%) received monitored anesthesia care. Patients who received monitored anesthesia care were more likely to be >80 years old (12.4% v 4.9%; p < 0.0001), female (36.1% v 34.3%; p < 0.0001), have American Society of Anesthesiologists physical status >III (17.28% v 10.48%; p < 0.0001), and reside in urban areas (62.23% v 53.37%; p < 0.0001). They received care in the Northeast (17.6% v 10.1%; p < 0.0001) at low-volume centers (median 224 v 284 procedures; p < 0.0001). Multivariate analysis revealed that each five-year increase in age, being female, and having an American Society of Anesthesiologists physical status >III resulted in a 7% (p < 0.0001), 9% (p = 0.032), and 200% (p < 0.0001) increased odds of receiving monitored anesthesia care, respectively. Requiring additional ablation of atria or of a second arrhythmia and residing outside the Northeast resulted in a decreased odds of monitored anesthesia care (adjusted odds ratio 0.24 [p=0.002] and < 0.5 [p < 0.03], respectively). For each 50 cases performed annually at a center, the odds decreased by 5% (p = 0.005). CONCLUSIONS: General anesthesia is the most common type of anesthesia administered for atrial fibrillation ablation. The type of anesthesia administered, however, varies with patient, procedural, and hospital characteristics.

Amiodarone is associated with adverse outcomes in patients with sustained ventricular arrhythmias upgraded to cardiac resynchronization therapy-defibrillators.

INTRODUCTION: Amiodarone reduces recurrent ventricular tachyarrhythmias (VTA) but may worsen cardiovascular outcomes in heart failure (HF) patients. Cardiac resynchronization therapy (CRT) may also be antiarrhythmic. When patients with prior sustained VTA are upgraded to CRT defibrillators (CRT-D) from conventional implantable cardioverter-defibrillators (ICDs), should concomitant amiodarone be continued or is CRT's antiarrhythmic potential sufficient? METHODS AND RESULTS: We identified 67 patients from a prospective CRT registry with spontaneous sustained VTA, New York Heart Association (NYHA) II-IV HF, and left bundle-branch block (LBBB) who were upgraded to CRT defibrillators from conventional ICDs. We compared changes in QRS duration and left ventricular ejection fraction (LVEF) pre- and post-CRT, time to death, transplant or ventricular assist device (VAD), and time to recurrent VTA therapies between 37 patients continuing amiodarone therapy and 30 amiodarone-naïve patients. Amiodarone-treated patients had worse renal function and a higher prevalence of prior VTA storm compared with amiodarone-naïve patients. After CRT, amiodarone-treated patients demonstrated less QRS narrowing (8 vs 20 ms; P = 0.021) and less LVEF improvement (-2.7 vs +5.2%; P = 0.006). Over 29 months, 31 (47%) patients died and 13 (20%) received transplant or VAD. Risk of death, transplant, or VAD was greater in amiodarone-treated than -naïve patients (corrected hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.12-4.11; P = 0.022). Appropriate CRT-D therapies occurred in 37 (55%) patients; amiodarone use was not associated time to first therapy (HR, 1.13; 95% CI, 0.59-2.16; P = 0.72). CONCLUSION: In patients with sustained VTA and LBBB upgraded from conventional ICDs to CRT defibrillators, concomitant amiodarone use is associated with less QRS narrowing, less LVEF improvement, greater risk of death, transplant, or VAD, and similar risk of recurrent VTA.

Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS.

BACKGROUND: Corticospinal tract (CST) degeneration and cortical atrophy are consistent features of amyotrophic lateral sclerosis (ALS). We hypothesised that neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, would reveal microstructural changes associated with ALS within the CST and precentral gyrus (PCG) 'in vivo'. METHODS: 23 participants with sporadic ALS and 23 healthy controls underwent diffusion MRI. Neurite density index (NDI), orientation dispersion index (ODI) and free water fraction (isotropic compartment (ISO)) were derived. Whole brain voxel-wise analysis was performed to assess for group differences. Standard diffusion tensor imaging (DTI) parameters were computed for comparison. Subgroup analysis was performed to investigate for NODDI parameter differences relating to bulbar involvement. Correlation of NODDI parameters with clinical variables were also explored. The results were accepted as significant where p<0.05 after family-wise error correction at the cluster level, clusters formed with p<0.001. RESULTS: In the ALS group NDI was reduced in the extensive regions of the CST, the corpus callosum and the right PCG. ODI was reduced in the right anterior internal capsule and the right PCG. Significant differences in NDI were detected between subgroups stratified according to the presence or absence of bulbar involvement. ODI and ISO correlated with disease duration. CONCLUSIONS: NODDI demonstrates that axonal loss within the CST is a core feature of degeneration in ALS. This is the main factor contributing to the altered diffusivity profile detected using DTI. NODDI also identified dendritic alterations within the PCG, suggesting microstructural cortical dendritic changes occur together with CST axonal damage.

Visual Perceptual Echo Reflects Learning of Regularities in Rapid Luminance Sequences.

A novel neural signature of active visual processing has recently been described in the form of the "perceptual echo", in which the cross-correlation between a sequence of randomly fluctuating luminance values and occipital electrophysiological signals exhibits a long-lasting periodic (∼100 ms cycle) reverberation of the input stimulus (VanRullen and Macdonald, 2012). As yet, however, the mechanisms underlying the perceptual echo and its function remain unknown. Reasoning that natural visual signals often contain temporally predictable, though nonperiodic features, we hypothesized that the perceptual echo may reflect a periodic process associated with regularity learning. To test this hypothesis, we presented subjects with successive repetitions of a rapid nonperiodic luminance sequence, and examined the effects on the perceptual echo, finding that echo amplitude linearly increased with the number of presentations of a given luminance sequence. These data suggest that the perceptual echo reflects a neural signature of regularity learning.Furthermore, when a set of repeated sequences was followed by a sequence with inverted luminance polarities, the echo amplitude decreased to the same level evoked by a novel stimulus sequence. Crucially, when the original stimulus sequence was re-presented, the echo amplitude returned to a level consistent with the number of presentations of this sequence, indicating that the visual system retained sequence-specific information, for many seconds, even in the presence of intervening visual input. Altogether, our results reveal a previously undiscovered regularity learning mechanism within the human visual system, reflected by the perceptual echo.SIGNIFICANCE STATEMENT How the brain encodes and learns fast-changing but nonperiodic visual input remains unknown, even though such visual input characterizes natural scenes. We investigated whether the phenomenon of "perceptual echo" might index such learning. The perceptual echo is a long-lasting reverberation between a rapidly changing visual input and evoked neural activity, apparent in cross-correlations between occipital EEG and stimulus sequences, peaking in the alpha (∼10 Hz) range. We indeed found that perceptual echo is enhanced by repeatedly presenting the same visual sequence, indicating that the human visual system can rapidly and automatically learn regularities embedded within fast-changing dynamic sequences. These results point to a previously undiscovered regularity learning mechanism, operating at a rate defined by the alpha frequency.

Response to Ruby et al: On a 'failed' attempt to manipulate conscious perception with transcranial magnetic stimulation to prefrontal cortex.

Does disruption of prefrontal cortical activity using transcranial magnetic stimulation (TMS) impair visual metacognition? An initial study supporting this idea (Rounis, Maniscalco, Rothwell, Passingham, & Lau, 2010) motivated an attempted replication and extension (Bor, Schwartzman, Barrett, & Seth, 2017). Bor et al. failed to replicate the initial study, concluding that there was not good evidence that TMS to dorsolateral prefrontal cortex impairs visual metacognition. This failed replication has recently been critiqued by some of the authors of the initial study (Ruby, Maniscalco, & Peters, 2018). Here we argue that these criticisms are misplaced. In our response, we encounter some more general issues concerning good practice in replication of cognitive neuroscience studies, and in setting criteria for excluding data when employing statistical analyses like signal detection theory. We look forward to further studies investigating the role of prefrontal cortex in metacognition, with increasingly refined methodologies, motivated by the discussions in this series of papers.

Miniaturized Robotic End-Effector with Piezoelectric Actuation and Fiber Optic Sensing for Minimally Invasive Cardiac Procedures.

Each year 35,000 cardiac ablation procedures are performed to treat atrial fibrillation through the use of catheter systems. The success rate of this treatment is highly dependent on the force which the catheter applies on the heart wall. If the magnitude of the applied force is much higher than a certain threshold the tissue perforates, whereas if the force is lower than this threshold the lesion size may be too large and is inconsistent. Furthermore, studies have shown large variability in the applied force from trained physicians during treatment, suggesting that physicians are unable to manually regulate the levels of the force at the site of treatment. Current catheter systems do not provide the physicians with active means for contact force control and are only at most aided by visual feedback of the forces measured in situ. This paper discusses a novel design of a robotic end-effector that integrates mechanisms of sensing and actively controlling of the applied forces into a miniaturized compact form. The required specifications for design and integration were derived from the current application under investigation. An off-the-shelf miniature piezoelectric motor was chosen for actuation, and a force sensing solution was developed to meet the specifications. Experimental characterization of the actuator and the force sensor within the integrated setup show compliance with the specifications and pave the way for future experimentation where closed-loop control of the system can be implemented according to the contact force control strategies for the application.

Left ventricular dimensions predict risk of appropriate shocks but not mortality in cardiac resynchronization therapy-defibrillator recipients with left bundle-branch block and non-ischemic cardiomyopathy.

AIMS: Patients with non-ischaemic cardiomyopathy (NICM) and left bundle-branch block (LBBB) often benefit markedly from cardiac resynchronization therapy (CRT). Cardiac resynchronization therapy responders have a lower risk of appropriate device shocks from CRT-defibrillators (CRT-D) than do non-responders. Larger baseline left ventricular (LV) dimensions may be associated with less CRT response and thus greater risk of appropriate shocks. METHODS AND RESULTS: We analysed all (n = 249; 55% female) primary prevention CRT-D recipients at our institution with LBBB, NICM, and measured LV dimensions prior to device implant for the outcomes of (i) appropriate shocks, (ii) any appropriate tachyarrhythmia therapies, and (iii) risk of death, transplant, or left ventricular assist device (LVAD). During 59 months (interquartile range 21.5-91.5) follow-up, 19 (8%) patients received ≥1 appropriate shock, and 67 (27%) patients died, received a transplant, or required LVAD. Receiver-operating characteristic analysis of LV end-diastolic diameter (LVEDD) per meter height vs. appropriate shock(s) revealed an area under the curve of 0.75 (95% CI 0.65-0.85; P < 0.001). No patient with indexed LVEDD <3.36 cm/m (n = 76) received a shock. There was no statistically significant difference in risk of death, transplant, or LVAD (corrected HR 1.67, 95% CI 0.90-3.03; P = 0.103) in patients with indexed LVEDD above this cut-off compared to those with smaller dimension. Among 102 patients with paired quantitative echocardiograms, there was no difference in LVEF change between patients with indexed LVEDD <3.36 cm/m (n = 27; median 11%) and larger (n = 75; median 14%). CONCLUSION: Patients with LVEDD <3.36 cm/m height prior to CRT-D implant in the setting of NICM and LBBB have minimal risk of appropriate shocks but similar risk of death, transplant- and LVAD and similar extent of LV functional improvement as patients with larger LVEDD. CRT-pacemakers may be appropriate in such patients.

Clinical outcomes in cardiac resynchronization therapy-defibrillator recipients 80 years of age and older.

AIMS: Very elderly patients have not been well-represented in the randomized trials that established the benefits of cardiac resynchronization therapy (CRT) in heart failure (HF) patients. We therefore compared clinical outcomes in CRT-defibrillator (CRT-D) recipients ≥80 and <80 years old. METHODS AND RESULTS: We compared mortality and time to first appropriate shock in 258 consecutive CRT-D patients ≥80 years old with New York Heart Association II-IV HF, left ventricular ejection fraction ≤35%, QRS duration ≥120 ms, and no prior sustained ventricular tachyarrhythmias to 1058 patients <80 years old implanted with CRT-D during the same timeframe. Comorbidities and medical therapy differed significantly between the groups. During 52 ± 36 months, 123 (48%) patients ≥80 and 474 (45%) patients <80 died; mortality was significantly higher among patients ≥80 [corrected hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.12-1.72; P = 0.003]. Among 258 patients ≥80 with device follow-up, only 20 (8%) received an appropriate shock compared with 172 (17%) shocks in 1053 patients <80 years old. Time to first appropriate shock was significantly shorter in patients <80 (corrected HR 0.51, 95% CI 0.30-0.87, P = 0.013). Older patients experienced 14 inappropriate shocks, and while life-threatening device complications were rare, complications related to the high-power components of the CRT-D system were not infrequent (n = 11). CONCLUSION: Mortality among CRT-D recipients ≥80 years old is higher than in younger patients but is not excessive. The risk of appropriate device shocks in older patients is relatively low and significantly less than in younger patients. These observations suggest that CRT-pacemakers should be given due consideration in elderly HF patients.

A novel toolkit to improve percutaneous subxiphoid needle access to the healthy pericardial sac.

INTRODUCTION: The current practice of percutaneous subxiphoid needle access to the "healthy" pericardial sac has significant limitations. We sought to examine the feasibility of a novel toolkit designed to improve this procedure. METHODS AND RESULTS: The toolkit included a pericardial access needle and a virtual imaging platform. The needle had a 0.036 inch outer diameter, abbreviated 25° bevel, and was electrically insulated except for two small surfaces recessed from the tip. Radiofrequency energy was delivered via these surfaces to facilitate pericardial perforation. The virtual imaging system demonstrated the needle in real time and in its entirety within the thoracic anatomy of the individual animal, which was reconstructed from computed tomographic images obtained preoperatively and registered to the operative field. In five large (40-60 kg) healthy pigs, percutaneous subxiphoid access to the sac using both anterior and posterior approaches was performed. Spatial inaccuracy was measured as the distance between the pericardial puncture site and the anterior or posterior descending coronary artery, the pericardium contiguous to which had been targeted by the needle. In each animal, pericardial access was gained at 4 discrete sites (2 anterior, 2 posterior). Inaccuracy was 4.2 ± 2.2 millimeters (range 0-8 millimeters) and did not differ significantly between anterior and posterior approaches. No damage to the epicardium or coronary arteries was observed. CONCLUSIONS: Percutaneous subxiphoid access to the pericardial sac utilizing this toolkit was feasible, including safety and reasonable accuracy.

Health and Economic Outcomes Associated with Use of an Antimicrobial Envelope as a Standard of Care for Cardiac Implantable Electronic Device Implantation.

INTRODUCTION: Infection of cardiac implanted electrical devices (CIED) is a problem. In selected patients, use of an "antibacterial envelope" (AIGISRx®) is associated with low CIED infection rates. The value of this device when used as a standard of care is unclear. METHODS AND RESULTS: Retrospective analysis of all patients (N = 1,476) who underwent CIED implantation at a single hospital. During the study period, some implanters used the AIGISRx as a standard of care (Yes-AIGISRx Group, N = 365), whereas others did not use it at all (No-AIGISRx Group, N = 1,111). A risk score based on preoperative factors was calculated for each patient. Rates of CIED infection within 6 months were measured, and associated costs were estimated. The Yes-AIGISRx and No-AIGISRx groups had similar preoperative infection risk. In the No-AIGISRx group, 19 infections were observed (1.7%), versus 0 in the Yes-AIGISRx group (P = 0.006). The 6-month mortality rate among patients with infection was significantly greater than among those without infection (15.7% vs. 4.5%, P = 0.021). The average hospital duration for infection care was 13 days. By extrapolating the infection rate and costs observed in the No-AIGISRx group to the Yes-AIGISRx group, we estimated that there would have been 6.2 additional infections costing approximately $340,000. This cost was similar to the actual cost of the devices in the Yes-AIGISRx group, estimated at $320,000. CONCLUSIONS: Standard of care use of an antibacterial envelope as a standard of care was associated with a significantly lower rate of CIED infection, and appeared to be economically reasonable. Prospective trials to address these findings may be worthwhile.

Relaxin suppresses atrial fibrillation by reversing fibrosis and myocyte hypertrophy and increasing conduction velocity and sodium current in spontaneously hypertensive rat hearts.

RATIONALE: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. OBJECTIVE: To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca²âº transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P<0.01 versus WKY), steeper CV restitution kinetics, greater collagen deposition, higher levels of transcripts for transforming growth factor-ß, metalloproteinase-2, metalloproteinase-9, collagen I/III, and reduced connexin 43 phosphorylation (P<0.05 versus WKY). Programmed stimulation triggered sustained AF in SHR (n=5/5) and SHR+V (n=4/4), but not in WKY (n=0/5) and SHR+RLX (n=1/8; P<0.01). RLX treatment reversed the transcripts for fibrosis, flattened CV restitution kinetics, reduced action potential duration at 90% recovery to baseline, increased CV (P<0.01), and reversed atrial hypertrophy (P<0.05). Independent of antifibrotic actions, RLX (0.1 µmol/L) increased Na⁺ current density, INa (≈2-fold in 48 hours) in human cardiomyocytes derived from inducible pluripotent stem cells (n=18/18; P<0.01). CONCLUSIONS: RLX treatment suppressed AF in SHR hearts by increasing CV from a combination of reversal of fibrosis and hypertrophy and by increasing INa. The study provides compelling evidence that RLX may provide a novel therapy to manage AF in humans by reversing fibrosis and hypertrophy and by modulating cardiac ionic currents.

CT-Electromagnetic Three-Dimensional Tracking for Renal Endovascular Sympathetic Ablation Catheter Positioning in an Animal Model.

PURPOSE: To examine the feasibility of a computed tomography (CT)-guided renal endoarterial ablation procedure. MATERIALS AND METHODS: Five large (40-60 kg) pigs were studied. Abdominal CT images that were obtained preoperatively were registered to the operative field, and subsequent virtual navigation of a multielectrode ablation catheter within the CT environment was performed. The ablation electrodes were visualized using an impedance technique. Ablation lesions were applied within each artery. Histologic analysis was performed to judge accuracy of the catheter location as portrayed in the virtual image. RESULTS: The error between virtual and actual lesion locations along the longitudinal plane of the artery was 3.0 mm ± 2.5 (range, 0-6 mm) in the left renal artery and 3.4 mm ± 2.7 (range, 0-7 mm; P = .7) in the right renal artery. The accuracy of circumferential localization of the electrode was 92% in the right artery and 88% in the left artery. CONCLUSIONS: These data demonstrate that a CT-guided renal artery ablation procedure is feasible.

A pilot study to assess benefit of atrial rhythm control after cardiac resynchronization therapy and atrioventricular node ablation.

BACKGROUND: Atrial fibrillation (AF) is frequently comorbid in patients receiving cardiac resynchronization therapy (CRT), and suppression is typically difficult. Herein, we sought to understand the benefit of atrial rhythm control in the setting of ventricular rate and regularity control induced by atrioventricular node (AVN) ablation. METHODS: Fifty-two patients with heart failure, persistent AF, left ventricular (LV) ejection fraction <35%, and left bundle branch block underwent cardiac resynchronization therapy (CRT) + AVN ablation, and were randomized to one of the following groups: (1) Atrial Rhythm Control (ARC); (2) AF. Patients were subsequently followed for up to 1 year. RESULTS: Similar numbers of patients in each group were lost to follow-up or have withdrawn (ARC two; AF three). Rhythm control in four patients in the ARC group was inadequate. Among the remaining patients, the incidence of death (ARC=1, AF=2) or left ventricular assist device +/- transplantation (ARC=2, AF=1) were similar. Among the remaining patients (ARC 16, AF 19), at 1 year, there were no significant differences in CRT response rate, Minnesota Living with Heart Failure survey score, 6-minute hall walk distance, ventricular tachyarrhythmia occurrence, or LV dimensions. A significantly higher hospital encounter rate among ARC patients was attributable to efforts to maintain uniform atrial rhythm. CONCLUSIONS: In this pilot study, no incremental benefit for ARC was apparent. A larger study will be necessary to adequately examine these issues.

Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission.

AIMS: Diabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure. METHODS AND RESULTS: We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models. CONCLUSION: Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

Impact of scar on SPECT assay of left ventricular contraction dyssynchrony.

PURPOSE: Many patients presently receiving cardiac resynchronization therapy (CRT) do not respond. A disproportionate number of nonresponders have ischemic cardiomyopathy, with significant left ventricular (LV) scar burden. Current selection criteria, such as electrocardiography or echocardiography, may not reliably portray the magnitude of CRT-remediable LV contraction dyssynchrony. Although phase analysis of gated single photon emission computed tomography (SPECT) image data is increasingly appreciated as a tool for quantifying dyssynchrony, its use in the setting of scar has not been adequately evaluated. METHODS: Consecutive patients with ischemic (ICM, n = 50) or nonischemic (NICM, n = 39) cardiomyopathy underwent SPECT imaging prior to receiving CRT. In each patient, phase analysis of the raw images was performed to yield a phase standard deviation (PSD), an index which varies directly with the magnitude of dyssynchrony. ICM patient image data were also reanalyzed after scarred segments were stripped away. RESULTS: Raw image analysis demonstrated that PSD was significantly larger among ICM (57 ± 17°) than NICM (35 ± 13°, p < 0.001) patients. Among ICM patients, PSD after stripping of scarred segments was significantly decreased (40 ± 13°, p < 0.001). Signals emanating from scarred segments were of low amplitude and presented a random pattern, suggestive of noise rather than indicating contraction. CONCLUSION: PSD values may be spuriously increased by scar. These findings may be important when using SPECT in selecting ischemic cardiomyopathy patients for CRT.

Computed tomographic analysis of left ventricular volumes and function after implantation of the Parachute® endoventricular partitioning device.

BACKGROUND: Preliminary clinical experience with a percutaneous endoventricular partitioning device (Parachute®, CardioKinetix Inc., Menlo Park, CA, USA) suggests that it ameliorates global LV dysfunction and heart failure symptoms in selected patients who have suffered previous anterior myocardial infarction. Less is known of its effect on regional LV function. OBJECTIVE: To gain insight into device effect on regional LV function by analysis of cardiac computed tomographic (CT) images obtained before and after device implantation. METHODS: Comparative analysis of pre and 6 months post-implantation contrast-enhanced CT images from 6 subjects enrolled in the phase 1 Parachute clinical trials, including regional LV volume and systolic excursion, as well as device motion. RESULTS: After implantation, a significant reduction in volume of the "dynamic" LV compartment (that which was not excluded by the device) was accompanied by a significant reduction in dykinetic motion and a trend toward an improved ejection fraction. Penetration of contrast into the excluded compartment was still present at 6 months, however the apical motion was significantly less dyskinetic in 3 subjects and unchanged in the other 3. Overall device surface motion was inward in systole, a significant improvement relative to the overall dyskinetic LV apex pre-implantation. Device motion was spatially heterogeneous, which appeared to be dependent on the motility of the myocardium that anchored its individual splines. CONCLUSIONS: Our data suggest that the Parachute device acts as a functional impediment to flow and stretch, effectively depressurizing the apical segment.

Single-photon emission computed tomographic-multidetector computed tomographic fusion image integration: a potential aid to left ventricular substrate ablation.

AIMS: To illustrate the feasibility of ventricular tachycardia (VT) ablation assisted by single photon emission computed tomography (SPECT)-multidetector (MDCT) computed tomography 'fusion' image guidance. METHODS AND RESULTS: A patient with ischaemic cardiomyopathy and recurrent VT underwent catheter ablation. Prior to the procedure, SPECT and MDCT had been obtained. A combined ('fusion') image was created, and this image was registered to the operative field using a commercial catheter navigation system. There was a close anatomic and electrophysiological correspondence between the left ventricular electroanatomic map obtained in the operating theatre and the fusion image. CONCLUSION: If accuracy of this technique can be confirmed, fusion image guidance may offer a significant value during catheter ablation of VT, including improved substrate detail and procedure abbreviation.