Trends in implantable cardioverter defibrillator and cardiac resynchronisation therapy lead parameters for patients with arrhythmogenic and dilated cardiomyopathies.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead parameters may deteriorate due to right ventricular (RV) disease such as arrhythmogenic right ventricular cardiomyopathy (ARVC), with implications for safe delivery of therapies. We compared ICD and CRT-D (cardiac resynchronisation therapy-defibrillator) lead parameters in patients with ARVC and dilated cardiomyopathy (DCM). METHODS: RV lead sensing (R wave amplitude) and pacing (threshold and amplitude-pulse width product (APWP)), left ventricular (LV) pacing (APWP), and imaging parameter trends were assessed in 18 patients with ARVC and 18 with DCM. RESULTS: R wave amplitude did not change significantly over time in either group (over 5 years, ARVC -0.4 mV, 95% CI -3.8-3.0 mV; DCM -1.8 mV, 95% CI -5.0-1.3 mV). Within ARVC group, divergent trends were seen according to lead position. DCM patients experienced an increase in RV lead threshold (+1.1 V over 5 years, 95% CI + 0.5 to +1.7 V) and RV APWP (+0.48 Vms over 5 years, 95% CI + 0.24 to +0.71 Vms); ARVC patients had no change. ARVC patients had a higher LVEF at baseline than DCM patients (52 vs 20%, p < 0.001), though LVEF decreased over time for the former, while increasing for the latter. TAPSE did not change over time for ARVC patients. CONCLUSIONS: Lead parameters in ARVC patients were stable over medium-term follow up. In DCM patients, RV lead threshold and RV and LV APWP increased over time. These differential responses for DCM and ARVC were not explained by imaging indices, and may reflect distinct patterns of disease progression.

Anticoagulation and the risk of complications in ventricular tachycardia and premature ventricular complex ablation.

BACKGROUND: Many patients undergoing ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation receive antithrombotic medications.  Their uninterrupted use has the potential to affect complication rates. We assessed the incidence of complications in a large cohort of patients undergoing these procedures, according to antithrombotic medication use. METHODS: From June 2014 to June 2016, 201 VT and PVC ablations were performed at a single center. We allocated patients to three groups: (A) anticoagulation group (international normalized ratio ≥ 1.5 or non-vitamin K anticoagulant or full-dose low-molecular-weight (LMW) heparin on day of procedure); (B) antithrombotic group (antiplatelet therapy and/or prophylactic LMW heparin on day of procedure); and (C) no antithrombotics group.  We assessed periprocedural complication rates in each group.  Multivariable analysis was performed. RESULTS: Group A (47 patients) had 8.5% procedural complication rate: one stroke, one pseudoaneurysm, one femoral artery occlusion, and one access site hematoma. In this group, 37 patients had femoral arterial and 18 had epicardial access. In Group B (46 patients), the complication rate was 6.5%: two cardiac tamponades and one pericardial effusion without compromise. Group C (108 patients) had a 5.6% complication rate: three cardiac tamponades (with one periprocedural death and one concomitant gastric vessel injury), one pericardial effusion without compromise, one stomach perforation, and two access site hematomas. Multivariable analysis did not show any significant predictors of complications, though age approached significance. CONCLUSIONS: Complication rates were not significantly different between groups. These findings suggest that VT and PVC ablation can be performed safely in patients with uninterrupted antithrombotic medications.

Tissue-Level Cardiac Electrophysiology Studied in Murine Myocardium Using a Microelectrode Array: Autonomic and Thermal Modulation.

Cardiac electrophysiology is regulated by the autonomic nervous system, and this has both pathophysiological, and possibly therapeutic importance. Furthermore, chamber differences in electrophysiology exist between atria and ventricles, yet there have been few direct comparisons. There is substantial literature on ion channel modulation at the single-cell level but less work on how this affects tissue-level parameters. We used a microelectrode array system to explore these issues using murine atrial and ventricular tissue slices. Activation time, conduction velocity and repolarisation were measured, and their modulation by temperature and pharmacological autonomic agonists were assessed. The system recorded reliable measurements under control conditions in the absence of drug/thermal challenge, and significant baseline differences were found in chamber electrophysiology. The sodium channel blocker mexiletine, produced large magnitude changes in all three measured parameters. Carbachol and isoprenaline induced differing effects in atria and ventricles, whereas temperature produced similar effects on activation and repolarisation.

Ripple mapping: Initial multicenter experience of an intuitive approach to overcoming the limitations of 3D activation mapping.

BACKGROUND: Ripple mapping (RM) displays electrograms as moving bars over a three-dimensional surface displaying bipolar voltage, and has shown in a single-center series to be effective for atrial tachycardia (AT) mapping without annotation of local activation time or window-of-interest assignment. We tested the reproducibility of these findings in operators naïve to RM, using it for the first time in postablation AT. METHODS: Maps were collected with multielectrode catheters and CARTO ConfiDENSE. A diagnosis of the tachycardia mechanism was made using RM and an assessment of operator confidence was made according to a three-grade scale (1 highest-3 lowest). RESULTS: The first 20 patients (64 ± 9 years, median two previous ablations) undergoing RM-guided AT ablation across five sites were studied. High-density maps (2,935 ± 1,328 points) in AT (CL = 296 ± 95 milliseconds) were collected. Macroreentrant ATs bordered by scar or anatomical obstacles were identified in n = 12 (60%), small reentrant ATs around scar in n = 3 (15%), and focal ATs from scar in n = 5 (25%). Diagnostic confidence with RM was grade 1 in n = 13 (65%), where operators felt confident to proceed to ablation without entrainment. Ablation offered the correct diagnosis n = 18 (90%). Retrospective review of the accompanying LAT maps demonstrated potential sources for error related to the window of interest selection, interpolation, and differentiating regions of scar during tachycardia on the voltage map. CONCLUSION: RM was easy to adopt by operators using it for the first time, and identified the correct target for ablation with high diagnostic confidence in most cases of complex AT.

Evaluation of ECG Imaging to Map Hemodynamically Stable and Unstable Ventricular Arrhythmias.

BACKGROUND: ECG imaging (ECGI) has been used to guide treatment of ventricular ectopy and arrhythmias. However, the accuracy of ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia (VT) in structurally abnormal hearts remains to be fully validated. METHODS: During catheter ablation of VT, simultaneous mapping was performed using electroanatomical mapping (CARTO, Biosense-Webster) and ECGI (CardioInsight, Medtronic) in 18 patients. Sites of entrainment, pace-mapping, and termination during ablation were used to define the VT site of origin (SoO). Distance between SoO and the site of earliest activation on ECGI were measured using co-registered geometries from both systems. The accuracy of ECGI versus a 12-lead surface ECG algorithm was compared. RESULTS: A total of 29 VTs were available for comparison. Distance between SoO and sites of earliest activation in ECGI was 22.6, 13.9 to 36.2 mm (median, first to third quartile). ECGI mapped VT sites of origin onto the correct AHA segment with higher accuracy than a validated 12-lead ECG algorithm (83.3% versus 38.9%; P=0.015). CONCLUSIONS: This simultaneous assessment demonstrates that CardioInsight localizes VT circuits with sufficient accuracy to provide a region of interest for targeting mapping for ablation. Resolution is not sufficient to guide discrete radiofrequency lesion delivery via catheter ablation without concomitant use of an electroanatomical mapping system but may be sufficient for segmental ablation with radiotherapy.

Simultaneous Comparison of Electrocardiographic Imaging and Epicardial Contact Mapping in Structural Heart Disease.

BACKGROUND: The accuracy of ECG imaging (ECGI) in structural heart disease remains uncertain. This study aimed to provide a detailed comparison of ECGI and contact-mapping system (CARTO) electrograms. METHODS: Simultaneous epicardial mapping using CARTO (Biosense-Webster, CA) and ECGI (CardioInsight) in 8 patients was performed to compare electrogram morphology, activation time (AT), and repolarization time (RT). Agreement between AT and RT from CARTO and ECGI was assessed using Pearson correlation coefficient, ρ AT and ρ RT, root mean square error, E AT and E RT, and Bland-Altman plots. RESULTS: After geometric coregistration, 711 (439-905; median, first-third quartiles) ECGI and CARTO points were paired per patient. AT maps showed ρ AT=0.66 (0.53-0.73) and E AT=24 (21-32) ms, RT maps showed ρ RT=0.55 (0.41-0.71) and E RT=51 (38-70) ms. The median correlation coefficient measuring the morphological similarity between the unipolar electrograms was equal to 0.71 (0.65-0.74) for the entire signal, 0.67 (0.59-0.76) for QRS complexes, and 0.57 (0.35-0.76) for T waves. Local activation map correlation, ρ AT, was lower when default filters were used (0.60 (0.30-0.71), P=0.053). Small misalignment of the ECGI and CARTO geometries (below ±4 mm and ±4°) could introduce variations in the median ρ AT up to ±25%. Minimum distance between epicardial pacing sites and the region of earliest activation in ECGI was 13.2 (0.0-28.3) mm from 25 pacing sites with stimulation to QRS interval <40 ms. CONCLUSIONS: This simultaneous assessment demonstrates that ECGI maps activation and repolarization parameters with moderate accuracy. ECGI and contact electrogram correlation is sensitive to electrode apposition and geometric alignment. Further technological developments may improve spatial resolution.

Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?

Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. In this review, we look at some of the lessons to be learned from approaches to arrhythmia prediction in patients, clinical trials of drugs used in the treatment of arrhythmias, and the implications for the design of pre-clinical safety pharmacology testing.