CArdiac MagnEtic resonance assessment of bi-Atrial fibrosis in secundum atrial septal defects patients: CAMERA-ASD study.

AIMS: Atrial septal defects (ASD) are associated with atrial arrhythmias, but the arrhythmia substrate in these patients is poorly defined. We hypothesized that bi-atrial fibrosis is present and that right atrial fibrosis is associated with atrial arrhythmias in ASD patients. We aimed to evaluate the extent of bi-atrial fibrosis in ASD patients and to investigate the relationships between bi-atrial fibrosis, atrial arrhythmias, shunt fraction, and age. METHODS AND RESULTS: Patients with uncorrected secundum ASDs (n = 36; 50.4 ± 13.6 years) underwent cardiac magnetic resonance imaging with atrial late gadolinium enhancement. Comparison was made to non-congenital heart disease patients (n = 36; 60.3 ± 10.5 years) with paroxysmal atrial fibrillation (AF). Cardiac magnetic resonance parameters associated with atrial arrhythmias were identified and the relationship between bi-atrial structure, age, and shunt fraction studied. Bi-atrial fibrosis burden was greater in ASD patients than paroxysmal AF patients (20.7 ± 14% vs. 10.1 ± 8.6% and 14.8 ± 8.5% vs. 8.6 ± 6.1% for right and left atria respectively, P = 0.001 for both). In ASD patients, right atrial fibrosis burden was greater in those with than without atrial arrhythmias (33.4 ± 18.7% vs. 16.8 ± 10.3%, P = 0.034). On receiver operating characteristic analysis, a right atrial fibrosis burden of 32% had a 92% specificity and 71% sensitivity for predicting the presence of atrial arrhythmias. Neither age nor shunt fraction was associated with bi-atrial fibrosis burden. CONCLUSION: Bi-atrial fibrosis burden is greater in ASD patients than non-congenital heart disease patients with paroxysmal AF. Right atrial fibrosis is associated with the presence of atrial arrhythmias in ASD patients. These findings highlight the importance of right atrial fibrosis to atrial arrhythmogenesis in ASD patients.

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

Fully Automatic Atrial Fibrosis Assessment Using a Multilabel Convolutional Neural Network.

BACKGROUND: Pathological atrial fibrosis is a major contributor to sustained atrial fibrillation. Currently, late gadolinium enhancement (LGE) scans provide the only noninvasive estimate of atrial fibrosis. However, widespread adoption of atrial LGE has been hindered partly by nonstandardized image processing techniques, which can be operator and algorithm dependent. Minimal validation and limited access to transparent software platforms have also exacerbated the problem. This study aims to estimate atrial fibrosis from cardiac magnetic resonance scans using a reproducible operator-independent fully automatic open-source end-to-end pipeline. METHODS: A multilabel convolutional neural network was designed to accurately delineate atrial structures including the blood pool, pulmonary veins, and mitral valve. The output from the network removed the operator dependent steps in a reproducible pipeline and allowed for automated estimation of atrial fibrosis from LGE-cardiac magnetic resonance scans. The pipeline results were compared against manual fibrosis burdens, calculated using published thresholds: image intensity ratio 0.97, image intensity ratio 1.61, and mean blood pool signal +3.3 SD. RESULTS: We validated our methods on a large 3-dimensional LGE-cardiac magnetic resonance data set from 207 labeled scans. Automatic atrial segmentation achieved a 91% Dice score, compared with the mutual agreement of 85% in Dice seen in the interobserver analysis of operators. Intraclass correlation coefficients of the automatic pipeline with manually generated results were excellent and better than or equal to interobserver correlations for all 3 thresholds: 0.94 versus 0.88, 0.99 versus 0.99, 0.99 versus 0.96 for image intensity ratio 0.97, image intensity ratio 1.61, and +3.3 SD thresholds, respectively. Automatic analysis required 3 minutes per case on a standard workstation. The network and the analysis software are publicly available. CONCLUSIONS: Our pipeline provides a fully automatic estimation of fibrosis burden from LGE-cardiac magnetic resonance scans that is comparable to manual analysis. This removes one key source of variability in the measurement of atrial fibrosis.

Pulmonary vein encirclement using an Ablation Index-guided point-by-point workflow: cardiovascular magnetic resonance assessment of left atrial scar formation.

AIMS: A point-by-point workflow for pulmonary vein isolation (PVI) targeting pre-defined Ablation Index values (a composite of contact force, time, and power) and minimizing interlesion distance may optimize the creation of contiguous ablation lesions whilst minimizing scar formation. We aimed to compare ablation scar formation in patients undergoing PVI using this workflow to patients undergoing a continuous catheter drag workflow. METHODS AND RESULTS: Post-ablation cardiovascular magnetic resonance imaging was performed in patients undergoing 1st-time PVI using a parameter-guided point-by-point workflow (n = 26). Total left atrial scar burden and the width and continuity of the pulmonary vein encirclement were determined on analysis of atrial late gadolinium enhancement sequences. Comparison was made with a cohort of patients (n = 20) undergoing PVI using continuous drag lesions. Mean post-ablation scar burden and scar width were significantly lower in the point-by-point group than in the control group (6.6 ± 6.8% vs. 9.6 ± 5.0%, P = 0.03 and 7.9 ± 3.6 mm vs. 10.7 ± 2.3 mm, P = 0.003). More complete bilateral pulmonary vein encirclements were seen in the point-by-point group (P = 0.038). All patients achieved acute PVI. CONCLUSION: Pulmonary vein isolation using a point-by-point workflow is feasible and results in a lower scar burden and scar width with more complete pulmonary vein encirclements than a conventional drag lesion approach.

A comprehensive multi-index cardiac magnetic resonance-guided assessment of atrial fibrillation substrate prior to ablation: Prediction of long-term outcomes.

INTRODUCTION: Multiple cardiac magnetic resonance (CMR)-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), left ventricular ejection fraction (LVEF), LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study. METHODS AND RESULTS: Eighty-nine patients (53% paroxysmal AF, 73% male) underwent comprehensive CMR study before first-time AF ablation (median follow-up 726 days [IQR: 418-1010 days]). The 3D late gadolinium-enhanced acquisition (1.5T, 1.3 × 1.3 × 2 mm) was quantified for fibrosis; LA volume and sphericity were assessed on manual segmentation at atrial diastole; LAEF and LVEF were quantified on multislice cine imaging. AF recurred in 43 patients (48%) overall (31 at 1 year). In the recurrence group, LA fibrosis was higher (42% vs 29%; hazard ratio [HR]: 1.032; P = .002), left atrial ejection fraction (LAEF) lower (25% vs 34%; HR: 0.063; P = .016) and LVEF lower (57% vs 63%; HR: 0.011; P = .008). LA volume (135 vs 124 mL) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (Model 1), additionally AF type (Model 2) and combined (Model 3). In Models 1 and 2, LA fibrosis, LAEF, and LVEF were independently associated with outcome, but only LA fibrosis was independent in Model 3 (HR: 1.021; P = .022). CONCLUSIONS: LAEF, LVEF, and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome.

Evaluation of a real-time magnetic resonance imaging-guided electrophysiology system for structural and electrophysiological ventricular tachycardia substrate assessment.

AIMS: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model. METHODS AND RESULTS: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ≥40 ms. Using conventional (0.5-1.5 mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5 mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 ± 6.0%, 35.0 ± 10.1%, and 90.4 ± 8.6%, respectively. CONCLUSION: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI.

The value of ablation parameter indices for predicting mature atrial scar formation in humans: An in vivo assessment using cardiac magnetic resonance imaging.

INTRODUCTION: The VisiTag module (CARTO3) provides an objective assessment of radiofrequency (RF) ablation parameters. This study aimed to determine the predictive value and optimal VisiTag threshold settings for prediction of gaps in mature atrial scar, as assessed non-invasively using cardiac magnetic resonance (CMR) imaging. METHODS: Twenty-four subjects (11 paroxysmal atrial fibrillation) underwent first-time RF ablation with operators blinded to VisiTag data. Three-dimensional late gadolinium enhancement (LGE) CMR scans were performed at 3 months (1.3 × 1.3 × 4 mm3 ). A survey of UK operators defined the standard VisiTag settings ("Force," 8 g; "Time," 10 seconds; "Percentage Time," 50%; "Range," 3 mm; "Impedance" and "Temperature" "off"). Each ablation procedure was exported 27 times, varying single VisiTag parameters from default values. The presence of gaps in VisiTag markers (18 sectors) was assessed for each export and compared with gaps in CMR enhancement. RESULTS: At default settings, VisiTag gaps were specific (97.5%) but less sensitive (50.4%) for CMR gaps. Sensitivity improved at higher thresholds (89.2% at 20 g, 85.6% at 30 seconds, 88.5% impedance 10 Ω, 92.8% temperature 42°C), but with a lower positive predictive value (PPV) (42.3%, 42.7%, 41.1%, and 37.7%, respectively, vs 90.9% at baseline). "Force" thresholds demonstrated stable PPV from 2 to 8 g (P = 0.24), but a rapid fall at forces more than 10 g. The binomial logistic regression model explained 41.7% of gaps; χ 2 (4), 148; P < 0.0001, correctly classifying 82% of cases (specificity 94.9%, sensitivity 56.8%). CONCLUSION: Gaps in VisiTags predict gaps in CMR LGE enhancement with high specificity at default settings. Sensitivity may be improved using more stringent thresholds but at the potential cost of unnecessary ablation, particularly when a force more than 10 g is stipulated.

Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change.

OBJECTIVE: Responders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker. METHODS: A decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016-2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years. RESULTS: At 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year. CONCLUSIONS: Implanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.

Cardiac CT assessment of tissue thickness at the ostium of the left atrial appendage predicts acute success of radiofrequency ablation.

BACKGROUND: Tissue thickness at the site of ablation is a determinant of lesion transmurality. We reported the feasibility, safety, and efficacy of longstanding persistent atrial fibrillation ablation, incorporating deliberate left atrial appendage (LAA) isolation and occlusion, and identified systematic differences in ostial LAA tissue thickness in a matched cohort of cadaveric specimens. METHODS: Preprocedural cardiac computed tomography (CCT) scans were acquired from 22 patients undergoing LAA isolation and subsequent occlusion. Using a novel CCT wall thickness algorithm, LAA ostial wall thickness was assessed in vivo, compared with measurements from the cadaveric specimens, and analyzed for differences between regions that demonstrated acute electrical reconnection and those that did not. RESULTS: Mean tissue thickness calculated for each LAA ostial quadrant was 2.1 (±0.6) mm (anterior quadrant), 1.9 (±0.4) mm (superior quadrant), 1.5 (±0.4) mm (posterior quadrant), and 1.8 (±0.7) mm (inferior quadrant). Tissue was significantly thicker in the anterior (P  =  0.004) and superior quadrants (P  =  0.014) than the posterior quadrant. Higher thickness measurements were recorded from quadrants demonstrated to be thicker from histology. Tissue was significantly thicker in regions that demonstrated acute electrical reconnection (1.9 (±0.6) mm) when compared with those that did not (1.6 (±0.5) mm) (P  =  0.008). CONCLUSIONS: CCT imaging may be used to detect differences in wall thickness at different atrial locations and success of LAA ablation may be affected by local tissue thickness. Atrial wall thickness may need to be considered as a metric to guide titration of radiofrequency energy for safe and successful ablation.

The Effect of Contact Force in Atrial Radiofrequency Ablation: Electroanatomical, Cardiovascular Magnetic Resonance, and Histological Assessment in a Chronic Porcine Model.

OBJECTIVES: This study sought to determine the effect of contact force (CF) on atrial lesion size, quality, and transmurality by using a chronic porcine model of radiofrequency ablation. BACKGROUND: CF is a major determinant of ventricular lesion formation, but uncertainty exists regarding the most appropriate CF parameters to safely achieve permanent, transmural lesions in the atria. METHODS: Intercaval linear ablation (30 W, 42°C, 17 ml/min irrigation) was performed in 8 Göttingen minipigs by using a force-sensing catheter with CF >20 g (high force) or <10 g (low force) at alternate ends of the line, separated by an intentional gap. Voltage mapping and cardiovascular magnetic resonance (CMR) imaging were performed pre-ablation, immediately after ablation, and at 2 months' post-procedure. Lesions were sectioned orthogonal to the axis of ablation to assess transmurality. RESULTS: Mean CF was 22.6 ± 11.4 g and 7.8 ± 4.0 g in the high and low CF regions. Acute tissue edema was greater with high CF, both caudally (7.0 mm vs. 4.6 mm; p = 0.016) and cranially (6.9 mm vs. 4.6 mm; p = 0.038). There was no difference in chronic lesion size (voltage mapping) or volume (late gadolinium enhancement CMR) between high and low CF regions. There was no difference in scar density (assessed by low-voltage criteria and late gadolinium enhancement signal intensity) or histological transmurality between high and low CF regions. CONCLUSIONS: Although high CF (>20 g) resulted in more acute tissue edema than low CF (<10 g), chronically there was no difference in lesion size, quality, or transmurality. Appropriate CF targets for atrial ablation may be lower than previously thought.

Comparing exercise interventions to increase persistence with physical exercise and sporting activity among people with hypertension or high normal blood pressure: study protocol for a randomised controlled trial.

BACKGROUND: Increasing physical activity is known to have health benefits for people with hypertension and related conditions. Current general practitioner referrals for gym-based exercise increase physical activity but meta-analyses show that while these are effective the absolute health risk reduction is small due to patients failing to maintain activity levels over time. This study assesses the effectiveness of two sports-oriented interventions that are intended to bridge the intention-behaviour gap and thus increase the likelihood of sustained increases in physical activity. METHODS/DESIGN: Four-arm randomised controlled trial. The study tests two types of intervention that are intended to increase physical activity among currently inactive 18- to 74-year-old people with hypertension or high-normal blood pressure. This study will assess the effectiveness of a 12-week sports-oriented exercise programme, the efficacy of a web-delivered self-help tool to promote and support sports participation and healthy behaviour change and the effect of these interventions in combination. The control arm will be a standard care general practitioner referral for gym-based exercise. Participants will be allocated using block randomisation. The first author and primary analyst is blinded to participant allocation. The primary outcome measures will be time spent in physical activity assessed in metabolic equivalent minutes per week using the International Physical Activity Questionnaire 1 year after commencement of the intervention. Secondary outcomes include increased involvement in sporting activity and biomedical health outcomes including change in body mass index, and waist and hip measurement and reductions in blood pressure. DISCUSSION: If proven to be superior to general practitioner referrals for gym-based exercise, these sports-oriented interventions would constitute low-cost alternatives. The next stage would be a full economic evaluation of the interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71952900 (7 June 2013).

Quantitative assessment of the effects of therapeutic hypothermia on early repolarization in idiopathic ventricular fibrillation survivors: a 7-year cohort study.

BACKGROUND: The early repolarization (ER) pattern on ECG is associated with an increased risk of idiopathic ventricular fibrillation (ID-VF). Hypothermia is known to result in similar electrocardiographic changes. In this retrospective cohort study, we examine the impact of therapeutic hypothermia on ER in survivors of cardiac arrest attributed to ID-VF and draw comparisons with a control group who experienced coronary artery disease-related VF (CAD-VF). METHODS AND RESULTS: All patients who had cardiac arrest and were treated with therapeutic hypothermia over a 7-year period were considered for inclusion in the study. Forty-three patients were identified with ID-VF or CAD-VF arrest. ECGs were obtained during cooling and again after rewarming. ECGs were digitized and assessed for the presence of ER by 2 independent observers. Cooling significantly increased the prevalence (74% during cooling versus 51% at baseline temperature; P=0.044) and mean amplitude (0.78±0.10 mV during cooling versus 0.56±0.09 mV at baseline temperature; P=0.038) of ER in the overall cohort. During cooling, ER was more common among survivors of ID-VF than of CAD-VF (100% versus 67%; P=0.043). ER magnitude was significantly greater among ID-VF survivors than CAD-VF survivors both during cooling (1.16±0.18 versus 0.70±0.11 mV; P=0.044) and at baseline temperature (1.02±0.21 versus 0.42±0.09 mV; P=0.005). CONCLUSIONS: Hypothermia increases both the prevalence and magnitude of ER in cardiac arrest survivors. Despite the association of ER with ID-VF, therapeutic hypothermia only increases ER amplitude in CAD-VF survivors.