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 cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES: Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS: Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS: Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS: Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS: The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS: The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003286. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Evaluation of oxygen prescription in relation to hospital admission rate in patients with chronic obstructive pulmonary disease.

BACKGROUND: Long term oxygen therapy (LTOT) has a strong evidence base in COPD patients with respiratory failure, but prescribing practices are recognized to need reform to ensure appropriate use and minimize costs. In the UK, since February 2006, all Home Oxygen prescription is issued by hospitals, making respiratory specialists totally in charge of home oxygen prescription. It has been widely noted that inappropriate home oxygen, often for intermittent use ("short burst"), is frequently prescribed in patients with COPD and related conditions with the intention to prevent hospital admissions outside of evidence based LTOT guidelines. We participated in a national Lung Improvement Project aimed at making LTOT use more evidence based. We utilised this unique opportunity of studying the effect of removal of oxygen from COPD patients (who did not meet LTOT criteria) on hospital admission rates. METHODS: Primary and secondary care data sources were used to identify patients with COPD in a single primary care trust who were admitted to hospital at least once due to COPD between April 2007 and November 2010. Admission rates were compared between LTOT users and non-users, adjusted for age and COPD severity. LTOT users were further studied for predictors of admission in those appropriately or inappropriately given oxygen according to NICE guidance, and for admissions before and after oxygen receipt, adjusting further for co-morbidity. Mortality and economic analyses were also conducted. RESULTS: Readmission was more likely in LTOT users (3.18 v 1.67 per patient, p<0.001) after adjustment for FEV1 and age by multiple regression. When stratifying by appropriateness of LTOT prescription, adjusting also for Charlson index and other covariates, FEV1 predicted admission in appropriate users but there were no predictors in inappropriate users. In longitudinal analyses admission rates did not differ either side of oxygen prescription in appropriate or inappropriate LTOT users. Specialist assessment resulted in cost savings due to reduced use of oxygen. CONCLUSIONS: Admission to hospital is more likely in LTOT users, independent of COPD severity. Oxygen use outside NICE guidance does not appear to prevent admissions.

Metastatic spinal cord compression as an oncology emergency: getting our act together.

BACKGROUND: Metastatic spinal cord compression is a dreaded complication of cancer affecting 5-10% of patients requiring urgent treatment. A clinical practice improvement project was carried out to review and fine tune the clinical pathway for the acute management of patients with metastatic spinal cord compression. OBJECTIVE: To improve the quality of care for metastatic spinal cord compression over 6 months by ensuring that >90% of patients receive definitive treatment within 24 h of radiological diagnosis. METHOD: Using clinical practice improvement project methodology, the clinical pathway of 17 patients treated with radiotherapy for metastatic spinal cord compression within the last 6 months were reviewed to identify gaps and delays in the system. Interventions to form a multidisciplinary acute spinal cord crisis team, fine tune clinical referral processes and formulate a standardized treatment protocol were then implemented. Post-intervention of 22 subsequent patients were monitored for time to start steroids and radiation therapy, length of stay and hospitalization bill. RESULTS: With the interventions implemented, the mean response time to start steroidal therapy was reduced from 8.4 to 2.6 days and radiotherapy from 9.9 to 3.9 days. These translated into shorter mean length of stay from 23.8 to 14.7 days and smaller hospitalization bill size from 13,723 to 8,808 Singapore dollars. CONCLUSION: A clinical practice improvement project, to improve the quality of care for patients with metastatic spinal cord compression, can shorten response time to start steroidal therapy and definitive radiotherapy resulting in shorter length of stay and smaller hospitalization bill.

Evaluation of an audit with feedback continuing medical education program for radiation oncologists.

BACKGROUND: Meta-analyses demonstrate audit with feedback (AWF) is effective continuing medical education (CME). However, efficacy varies between specialties, with little published radiation oncologist (RO)-specific evidence. We evaluated an AWF CME intervention for ROs determining efficacy, cost-effectiveness, and participant satisfaction. METHODS: CME program: The CME incorporated fortnightly random patient chart audit, scoring management adequacy via a checklist. Scores were presented at a same-day institutional meeting, and case management discussed. Senior peers provided individualized, educational feedback. EVALUATION: Changes in behavior and performance were evaluated by chart review of new patients seen by ROs in the 2 months before commencement of AWF (T0), and at months 13-14 of the program (T1). Behavior and performance were evaluated with a validated, reproducible, 19-item instrument. Criteria for each case audited included 10 targeted and 3 nontargeted behavior items and 6 performance items; each scored 1 point if deemed adequate (maximum score 19). Cost-effectiveness was reported as cost to the institution per item point gained. The mean score (out of 5) of a 14-item questionnaire evaluated program perception. RESULTS: A total of 113 and 118 charts were evaluated at T0 and T1, respectively. Mean score of targeted behavior improved between T0 and T1 (from 8.7 to 9.2 out of 10, P = .0001), with no significant improvement of nontargeted behavior/performance items. Annual costs and cost-per-point gained were US 7,897 dollars and 15 dollars. Participant satisfaction was positive, increasing after efficacy result distribution (P = .0001). CONCLUSION: Audit with comparative, individualized, educational feedback is cost-effective and positively perceived CME, significantly improving targeted RO behavior. Oncologists' CME design and evaluation require further research.