Person:

Josephson, Mark

Electro-anatomical voltage mapping (EAM) is an invasive technique used for the identification of ventricular tachycardia (VT) substrate and subsequent guidance of VT ablation [1]. The mapping of VT substrate is very time consuming procedure, requires highly skilled electrophysiologist, is associated with patient risk and is an invasive procedure. Late gadolinium enhancement (LGE) MRI allows non-invasive evaluation of 3D structure of scar. Therefore, LGE has the potential to identify the VT substrate and can now be integrated in the current clinical platform for guidance of VT ablation as a roadmap. However, fusion of the two imaging modality is very challenging due to respiratory and cardiac motion during the mapping which results in large errors in data fusion. Our aim in this study is to develop a novel algorithm to detect the respiratory and cardiac-induced motion of the mapping catheter during the VT ablation to facilitate integration of LGE MRI to EAM data.

Summary. We assess left atrial scar using late gadolinium enhancement (LGE) with isotropic spatial resolution of (1.4^3 mm^3) by using highly accelerated LOST [1] reconstruction. Background. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia [2]. Pulmonary vein isolation (PVI) using radiofrequency (RF)-ablation is the leading treatment for AF. Recently, LGE imaging of the LA has been used to identify atrial wall scar due to RF-ablation [3]. However, current LGE methods have limited spatial resolution that substantially impact assessment of scar in the complex geometry of PVs and LA. In this study, we sought to utilize prospective random k-space sampling and LOST [1] for accelerated LGE imaging, where reduction in imaging time was traded-off for improved isotropic spatial-resolution. Methods. 23 patients with history of AF (6 females, (58.1 \pm 9.6) years, 9 pre-PVI, 2 with history of PVI; 8 post-PVI; 3 with both pre and post-PVI) were recruited for this study. LGE images were acquired 10-to-20 minutes after bolus infusion of 0.2 mmol/kg Gd-DTPA. Free-breathing ECG-triggered navigator-gated inversion-recovery GRE sequences were used for all acquisitions ((TR/TE/ \alpha = 5.2/2.6ms/25°, FOV=320×320×100mm)). The PV inflow artifact reduction technique in [4] was also utilized. For each patient, a standard non-isotropic 3D LGE scan ((1.4×1.4×4.0mm^3)) and a 3-fold-accelerated highresolution 3D LGE scan ((1.4^3 mm^3)) were performed, with randomized acquisition order. For random undersampling, central k-space (45×35 in ky-kz) was fullysampled, edges randomly discarded, and phase reordering performed as in [5]. Acquisition times were ~4 mins assuming 100% scan-efficiency at 70bpm for both scans. All undersampled data were reconstructed offline using LOST [1]. LOST-reconstructed high-resolution, and standard LGE images were scored by two blinded readers for diagnostic value, presence of LGE(yes/no); and image quality in axial(Ax), coronal(Co) and sagittal (Sa) views (1=poor,4=excellent). Results. Three cases were declared non-diagnostic due to contrast-washout and imperfect inversion-time. LGE was visually present in 14 of the remaining 20 patients based on standard-LGE images, and 12 based on LOST-reconstructed ones (disagreement on one pre- and one postPVI patient). Figure 1 and 2 show comparisons of isotropic vs. non-isotropic LGE images in two patients. Image scores for LOST-LGE: ( Ax=2.90 \pm 0.70, Sa=3.33 \pm 0.66, Co=3.00 \pm 0.63); and standard LGE: (Ax=3.76 \pm 0.54, Sa=2.48 \pm 0.60, Co=2.24 \pm 0.44), where differences were significant in all views. Conclusions. LOST allows isotropic spatial-resolution in LGE for assessment of LA and PV scar. Isotropic resolution allows reformatting LGE images in any orientation and facilitates assessment of scar. Further clinical study is needed to assess if the improved spatial resolution will impact the diagnostic interpretation of data.

Aims Cardiovascular magnetic resonance (MR) provides non-invasive assessment of early (24-hour) edema and injury following pulmonary vein isolation (by ablation) and subsequent scar formation. We hypothesize that 24-hours after ablation, cardiovascular MR would demonstrate a pattern of edema and injury due to ablation and the severity would correlate with subsequent scar. Methods: Fifteen atrial fibrillation patients underwent cardiovascular MR prior to pulmonary vein isolation, 24-hours post (N = 11) and 30-days post (N = 7) ablation, with T2-weighted (T2W) and late gadolinium enhancement (LGE) imaging. Left atrial wall thickness, edema enhancement ratio and LGE enhancement were assessed at each time point. Volumes of LGE and edema enhancement were measured, and the circumferential presence of injury was assessed at 24-hours, including comparison with LGE enhancement at 30 days. Results: Left atrial wall thickness was increased 24-hours post-ablation (10.7±4.1 mm vs. 7.0±1.8 mm pre-PVI, p<0.05). T2W enhancement at 24-hours showed increased edema enhancement ratio (1.5±0.4 for post-ablation, vs. 0.9±0.2 pre-ablation, p<0.001). Edema and LGE volumes at 24-hours were correlated with 30-day LGE volume (R = 0.76, p = 0.04, and R = 0.74, p = 0.09, respectively). Using a 16 segment model for assessment, 24-hour T2W had sensitivity, specificity, and accuracy of 82%, 63%, and 79% respectively, for predicting 30-day LGE. 24-hour LGE had sensitivity, specificity, and accuracy of 91%, 47%, and 84%. Conclusions: Increased left atrial wall thickening and edema were characterized on cardiovascular MR early post-ablation, and found to correlate with 30-day LGE scar.

Accurate fusion of late gadolinium enhancement magnetic resonance imaging (MRI) and electro-anatomical voltage mapping (EAM) is required to evaluate the potential of MRI to identify the substrate of ventricular tachycardia. However, both datasets are not acquired at the same cardiac phase and EAM data is corrupted with respiratory motion limiting the accuracy of current rigid fusion techniques. Knowledge of cardiac and respiratory motion during EAM is thus required to enhance the fusion process. In this study, we propose a novel approach to characterize both cardiac and respiratory motion from EAM data using the temporal evolution of the 3D catheter location recorded from clinical EAM systems. Cardiac and respiratory motion components are extracted from the recorded catheter location using multi-band filters. Filters are calibrated for each EAM point using estimates of heart rate and respiratory rate. The method was first evaluated in numerical simulations using 3D models of cardiac and respiratory motions of the heart generated from real time MRI data acquired in 5 healthy subjects. An accuracy of 0.6–0.7 mm was found for both cardiac and respiratory motion estimates in numerical simulations. Cardiac and respiratory motions were then characterized in 27 patients who underwent LV mapping for treatment of ventricular tachycardia. Mean maximum amplitude of cardiac and respiratory motion was 10.2±2.7 mm (min = 5.5, max = 16.9) and 8.8±2.3 mm (min = 4.3, max = 14.8), respectively. 3D Cardiac and respiratory motions could be estimated from the recorded catheter location and the method does not rely on additional imaging modality such as X-ray fluoroscopy and can be used in conventional electrophysiology laboratory setting.

Background: The relationship between pulmonary vein (PV) anatomy and successful catheter ablation of atrial fibrillation (AF) is poorly understood Methods: First-pass contrast enhanced PV magnetic resonance angiography was performed in 71 consecutive patients prior to PV isolation. PV diameter and cross-sectional area (CSA) were measured prior to PV isolation. Any symptomatic or asymptomatic AF >10s was considered a recurrence. Early recurrence was defined as recurrent AF ≤30 days after PV isolation, while late recurrence of AF was defined as recurrent AF >30 days after. Results: At 1 year, 57 % had any recurrence of AF while 41 % had late recurrence of AF. Study subjects with one or more PV diameter in the top 10th percentile had trend toward more early recurrent AF (HR 1.99, p = 0.053). Study subjects with one or more PV CSA in the top 10th percentile had more late recurrent AF (HR 2.25, p = 0.039) and a trend toward more early recurrent AF (HR 1.94, p = 0.064). With multivariate analysis, PV size was not associated with early recurrent AF, but late recurrent AF was associated with one or more large PV, increased left atrial size, and non-paroxysmal AF. Study subjects with all three of these risk factors had a 100 % rate of late recurrent AF at 1 year, while those with none had a 7 % rate of late recurrent AF. Conclusions: Larger PV size is independently associated with more late recurrent AF after PV isolation. Determination of PV size prior to PV isolation may predict procedural success.

Background: Anatomic atrial enlargement is associated with significant morbidity and mortality. However, atrial enlargement may not correlate with clinical measures such as electrocardiographic (ECG) criteria. Past studies correlating ECG criteria with anatomic measures mainly used inferior M-mode or two-dimensional echocardiographic data. We sought to determine the accuracy of the ECG to predict anatomic atrial enlargement as determined by volumetric cardiovascular magnetic resonance (CMR). Methods: ECG criteria for left (LAE) and right atrial enlargement (RAE) were compared to CMR atrial volume index measurements for 275 consecutive subjects referred for CMR (67% males, 51 (\pm) 14 years). ECG criteria for LAE and RAE were assessed by an expert observer blinded to CMR data. Atrial volume index was computed using the biplane area-length method. Results: The prevalence of CMR LAE and RAE was 28% and 11%, respectively, and by any ECG criteria was 82% and 5%, respectively. Though nonspecific, the presence of at least one ECG criteria for LAE was 90% sensitive for CMR LAE. The individual criteria P mitrale, P wave axis < (30^\circ), and negative P terminal force in V1 (NPTF-V1) > 0.04(s{\cdot}mm) were 88–99% specific although not sensitive for CMR LAE. ECG was insensitive but 96–100% specific for CMR RAE. Conclusion: The presence of at least one ECG criteria for LAE is sensitive but not specific for anatomic LAE. Individual criteria for LAE, including P mitrale, P wave axis < (30^\circ), or NPTF-V1 > 0.04(s{\cdot}mm) are highly specific, though not sensitive. ECG is highly specific but insensitive for RAE. Individual ECG P wave changes do not reliably both detect and predict anatomic atrial enlargement.

Background: Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results: Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration ≥120 ms were excluded. The mean spatial TT′ angle was 5.21±3.55°. During a median of 14 years of follow‐up, 235 SCDs occurred (1.24 per 1000 person‐years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT′ angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P<0.0001). A mean TT′ angle >90th percentile (>9.57°) was associated with a 2‐fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T‐vector amplitude ≥0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT′ angle and age was found: TT′ angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged ≥55 years (Pinteraction=0.009). Conclusions: In a large, prospective, community‐based cohort of left ventricular hypertrophy–free participants, increased beat‐to‐beat spatiotemporal variability in the T vector, as assessed by increasing TT′ angle, was associated with SCD.

Background: Identifying individuals at risk for sudden cardiac death (SCD) is of critical importance. Electrocardiographic (ECG) deep terminal negativity of P wave in V1 (DTNPV1), a marker of left atrial abnormality, has been associated with increased risk of all‐cause and cardiovascular mortality. We hypothesized that DTNPV1 is associated with increased risk of sudden cardiac death (SCD). Methods and Results: This analysis included 15 375 participants (54.1±5.8 years, 45% men, 73% whites) from the Atherosclerosis Risk in Communities (ARIC) study. DTNPV1 was defined from the resting 12‐lead ECG as presence of biphasic P wave (positive/negative) in V1 with the amplitude of the terminal negative phase >100 μV, or one small box on ECG scale. After a median of 14 years of follow‐up, 311 cases of SCD occurred. In unadjusted Cox regression, DTNPV1 was associated with an 8‐fold increased risk of SCD (HR 8.21; [95%CI 5.27 to 12.79]). Stratified by race and study center, and adjusted for age, sex, coronary heart disease (CHD), and ECG risk factors, as well as atrial fibrillation (AF), stroke, CHD, and heart failure (HF) as time‐updated variables, the risk of SCD associated with DTNPV1 remained significant (2.49, [1.51–4.10]). DTNPV1 improved reclassification: additional 3.4% of individuals were appropriately reclassified into a higher SCD risk group, as compared with traditional CHD risk factors alone. In fully adjusted models DTNPV1 was associated with increased risk of non‐fatal events: AF (5.02[3.23–7.80]), CHD (2.24[1.43–3.53]), HF (1.90[1.19–3.04]), and trended towards increased risk of stroke (1.88[0.99–3.57]). Conclusion: DTNPV1 is predictive of SCD suggesting its potential utility in risk stratification in the general population.