Non-invasive localization of post-infarct ventricular tachycardia exit sites to guide ablation planning: a computational deep learning platform utilizing the 12-lead electrocardiogram and intracardiac electrograms from implanted devices.

AIMS: Existing strategies that identify post-infarct ventricular tachycardia (VT) ablation target either employ invasive electrophysiological (EP) mapping or non-invasive modalities utilizing the electrocardiogram (ECG). Their success relies on localizing sites critical to the maintenance of the clinical arrhythmia, not always recorded on the 12-lead ECG. Targeting the clinical VT by utilizing electrograms (EGM) recordings stored in implanted devices may aid ablation planning, enhancing safety and speed and potentially reducing the need of VT induction. In this context, we aim to develop a non-invasive computational-deep learning (DL) platform to localize VT exit sites from surface ECGs and implanted device intracardiac EGMs. METHODS AND RESULTS: A library of ECGs and EGMs from simulated paced beats and representative post-infarct VTs was generated across five torso models. Traces were used to train DL algorithms to localize VT sites of earliest systolic activation; first tested on simulated data and then on a clinically induced VT to show applicability of our platform in clinical settings. Localization performance was estimated via localization errors (LEs) against known VT exit sites from simulations or clinical ablation targets. Surface ECGs successfully localized post-infarct VTs from simulated data with mean LE = 9.61 ± 2.61 mm across torsos. VT localization was successfully achieved from implanted device intracardiac EGMs with mean LE = 13.10 ± 2.36 mm. Finally, the clinically induced VT localization was in agreement with the clinical ablation volume. CONCLUSION: The proposed framework may be utilized for direct localization of post-infarct VTs from surface ECGs and/or implanted device EGMs, or in conjunction with efficient, patient-specific modelling, enhancing safety and speed of ablation planning.

The benefits of a home non-invasive ventilation retrieval service: Improved effectiveness and environmental sustainability in challenging times.

In the last 6 months, home non-invasive ventilation (NIV) services have faced several unanticipated challenges to their effectiveness and delivery as the result of a 'perfect storm' of the COVID-19 pandemic demands. We developed and delivered an innovative follow-up service, to support home NIV delivery, and improve cost-effectiveness and sustainability during COVID-19. Between Feb-2019 and Nov-2020, 92 post-acute patients were issued with home NIV; 25 (27%) out of the 92 patients had unused NIV machines successfully retrieved. The median (IQR) days of home NIV usage were 207 (98) for patients who had their machines returned. All the unused NIV machines retrieved were within the 5-year working life guaranteed by the manufacturer and were all redeployed after appropriate reconditioning and infection control measures. Without the home-visiting and recycling pilot, we would have relied on patients and families to return the unused machines. Given the expected disruption to NIV machine supply for at least the foreseeable 12-18 months, we feel it is important to get this important message out to other home NIV services urgently. Wider implementation of this novel approach could increase the availability of this vital resource and help meet the current demand on home NIV services.

Contrast-free high-resolution 3D magnetization transfer imaging for simultaneous myocardial scar and cardiac vein visualization.

OBJECTIVE: To develop a three-dimensional (3D) high-resolution free-breathing magnetization transfer ratio (MTR) sequence for contrast-free assessment of myocardial infarct and coronary vein anatomy. MATERIALS AND METHODS: Two datasets with and without off-resonance magnetization transfer preparation were sequentially acquired to compute MTR. 2D image navigators enabled beat-to-beat translational and bin-to-bin non-rigid motion correction. Two different imaging sequences were explored. MTR scar localization was compared against 3D late gadolinium enhancement (LGE) in a porcine model of myocardial infarction. MTR variability across the left ventricle and vessel sharpness in the coronary veins were evaluated in healthy human subjects. RESULTS: A decrease in MTR was observed in areas with LGE in all pigs (non-infarct: 25.1 ± 1.7% vs infarct: 16.8 ± 1.9%). The average infarct volume overlap on MTR and LGE was 62.5 ± 19.2%. In humans, mean MTR in myocardium was between 37 and 40%. Spatial variability was between 15 and 20% of the mean value. 3D whole heart MT-prepared datasets enabled coronary vein visualization with up to 8% improved vessel sharpness for non-rigid compared to translational motion correction. DISCUSSION: MTR and LGE showed agreement in infarct detection and localization in a swine model. Free-breathing 3D MTR maps are feasible in humans but high spatial variability was observed. Further clinical studies are warranted.

Non-contrast enhanced simultaneous 3D whole-heart bright-blood pulmonary veins visualization and black-blood quantification of atrial wall thickness.

PURPOSE: Pre-interventional assessment of atrial wall thickness (AWT) and of subject-specific variations in the anatomy of the pulmonary veins may affect the success rate of RF ablation procedures for the treatment of atrial fibrillation (AF). This study introduces a novel non-contrast enhanced 3D whole-heart sequence providing simultaneous information on the cardiac anatomy-including both the arterial and the venous system-(bright-blood volume) and AWT (black-blood volume). METHODS: The proposed MT-prepared bright-blood and black-blood phase sensitive inversion recovery (PSIR) BOOST framework acquires 2 differently weighted bright-blood volumes in an interleaved fashion. The 2 data sets are then combined in a PSIR-like reconstruction to obtain a complementary black-blood volume for atrial wall visualization. Image-based navigation and non-rigid respiratory motion correction are exploited for 100% scan efficiency and predictable acquisition time. The proposed approach was evaluated in 11 healthy subjects and 4 patients with AF scheduled for RF ablation. RESULTS: Improved depiction of the cardiac venous system was obtained in comparison to a T2 -prepared BOOST implementation, and quantified AWT was shown to be in good agreement with previously reported measurements obtained in healthy subjects (right atrium AWT: 2.54 ± 0.87 mm, left atrium AWT: 2.51 ± 0.61 mm). Feasibility for MT-prepared BOOST acquisitions in patients with AF was demonstrated. CONCLUSION: The proposed motion-corrected MT-prepared BOOST sequence provides simultaneous non-contrast pulmonary vein depiction as well as black-blood visualization of atrial walls. The proposed sequence has a large spectrum of potential clinical applications and further validation in patients is warranted.

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.

Left atrial effective conducting size predicts atrial fibrillation vulnerability in persistent but not paroxysmal atrial fibrillation.

BACKGROUND: The multiple wavelets and functional re-entry hypotheses are mechanistic theories to explain atrial fibrillation (AF). If valid, a chamber's ability to support AF should depend upon the left atrial size, conduction velocity (CV), and refractoriness. Measurement of these parameters could provide a new therapeutic target for AF. We investigated the relationship between left atrial effective conducting size (LAECS ), a function of area, CV and refractoriness, and AF vulnerability in patients undergoing AF ablation. METHODS AND RESULTS: Activation mapping was performed in patients with paroxysmal (n = 21) and persistent AF (n = 18) undergoing pulmonary vein isolation. Parameters used for calculating LAECS were: (a) left atrial body area (A); (b) effective refractory period (ERP); and (c) total activation time (T). Global CV was estimated as √A/T . Effective atrial conducting size was calculated as LAECS=A/(CV×ERP) . Post ablation, AF inducibility testing was performed. The critical LAECS required for multiple wavelet termination was determined from computational modeling. LAECS was greater in patients with persistent vs paroxysmal AF (4.4 ± 2.0 cm vs 3.2 ± 1.4 cm; P = .049). AF was inducible in 14/39 patients. LAECS was greater in AF-inducible patients (4.4 ± 1.8 cm vs 3.3 ± 1.7 cm; P = .035, respectively). The difference in LAECS between inducible and noninducible patients was significant in patients with persistent (P = .0046) but not paroxysmal AF (P = .6359). Computational modeling confirmed that LAECS > 4 cm was required for continuation of AF. CONCLUSIONS: LAECS measured post ablation was associated with AF inducibility in patients with persistent, but not paroxysmal AF. These data support a role for this method in electrical substrate assessment in AF patients.

Improved co-registration of ex-vivo and in-vivo cardiovascular magnetic resonance images using heart-specific flexible 3D printed acrylic scaffold combined with non-rigid registration.

BACKGROUND: Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI). METHODS: Seven weeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient. RESULTS: LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p < 0.0001) and there was a significantly greater change in the short axis dimensions in the control group (ratio of short axis dimensions in control and experimental group 0.38 vs 0.79, p < 0.001). In the experimental group, prior to non-rigid co-registration the LV cavity contracted isotropically in the ex-vivo condition by less than 20% in each dimension. There was a significant proportional change in tissue thickness in the healthy myocardium (change = 29 ± 21%), but not in dense scar (change = - 2 ± 2%, p = 0.034). Following the non-rigid co-registration step of the process, the DICE similarity coefficients for the myocardium, LV cavity and scar were 0.93 (±0.02), 0.89 (±0.01) and 0.77 (±0.07) respectively and the myocardial tissue and LV cavity volumes had a ratio of 1.03 and 1.00 respectively. CONCLUSIONS: The pattern of the morphological changes seen between the in-vivo and the ex-vivo LV differs between scar and healthy myocardium. A 3D printed flexible scaffold based on the in-vivo shape of the LV cavity is an effective strategy to minimize morphological changes in the ex-vivo LV. The subsequent non-rigid registration step further improved the co-registration and local comparison between in-vivo and ex-vivo data.

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.

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.

Magnetic resonance imaging guidance for the optimization of ventricular tachycardia ablation.

Catheter ablation has an important role in the management of patients with ventricular tachycardia (VT) but is limited by modest long-term success rates. Magnetic resonance imaging (MRI) can provide valuable anatomic and functional information as well as potentially improve identification of target sites for ablation. A major limitation of current MRI protocols is the spatial resolution required to identify the areas of tissue responsible for VT but recent developments have led to new strategies which may improve substrate assessment. Potential ways in which detailed information gained from MRI may be utilized during electrophysiology procedures include image integration or performing a procedure under real-time MRI guidance. Image integration allows pre-procedural magnetic resonance (MR) images to be registered with electroanatomical maps to help guide VT ablation and has shown promise in preliminary studies. However, multiple errors can arise during this process due to the registration technique used, changes in ventricular geometry between the time of MRI and the ablation procedure, respiratory and cardiac motion. As isthmus sites may only be a few millimetres wide, reducing these errors may be critical to improve outcomes in VT ablation. Real-time MR-guided intervention has emerged as an alternative solution to address the limitations of pre-acquired imaging to guide ablation. There is now a growing body of literature describing the feasibility, techniques, and potential applications of real-time MR-guided electrophysiology. We review whether real-time MR-guided intervention could be applied in the setting of VT ablation and the potential challenges that need to be overcome.

Patient-specific simulations predict efficacy of ablation of interatrial connections for treatment of persistent atrial fibrillation.

AIMS: Treatments for persistent atrial fibrillation (AF) offer limited efficacy. One potential strategy aims to return the right atrium (RA) to sinus rhythm (SR) by ablating interatrial connections (IAC) to isolate the atria, but there is limited clinical data to evaluate this ablation approach. We aimed to use simulation to evaluate and predict patient-specific suitability for ablation of IAC to treat AF. METHODS AND RESULTS: Persistent AF was simulated in 12 patient-specific geometries, incorporating electrophysiological heterogeneity and fibres, with IAC at Bachmann's bundle, the coronary sinus, and fossa ovalis. Simulations were performed to test the effect of left atrial (LA)-to-RA frequency gradient and fibrotic remodelling on IAC ablation efficacy. During AF, we simulated ablation of one, two, or all three IAC, with or without pulmonary vein isolation and determined if this altered or terminated the arrhythmia. For models without structural remodelling, ablating all IAC terminated RA arrhythmia in 83% of cases. Models with the LA-to-RA frequency gradient removed had an increased success rate (100% success). Ablation of IACs is less effective in cases with fibrotic remodelling (interstitial fibrosis 50% success rate; combination remodelling 67%). Mean number of phase singularities in the RA was higher pre-ablation for IAC failure (success 0.6 ± 0.8 vs. failure 3.2 ± 2.5, P < 0.001). CONCLUSION: This simulation study predicts that IAC ablation is effective in returning the RA to SR for many cases. Patient-specific modelling approaches have the potential to stratify patients prior to ablation by predicting if drivers are located in the LA or RA. We present a platform for predicting efficacy and informing patient selection for speculative treatments.

Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study.

Aims: Magnetic resonance imaging (MRI) is the gold standard for defining myocardial substrate in 3D and can be used to guide ventricular tachycardia ablation. We describe the feasibility of using a prototype magnetic resonance-guided electrophysiology (MR-EP) system in a pre-clinical model to perform real-time MRI-guided epicardial mapping, ablation, and lesion imaging with active catheter tracking. Methods and results: Experiments were performed in vivo in pigs (n = 6) using an MR-EP guidance system research prototype (Siemens Healthcare) with an irrigated ablation catheter (Vision-MR, Imricor) and a dedicated electrophysiology recording system (Advantage-MR, Imricor). Following epicardial access, local activation and voltage maps were acquired, and targeted radiofrequency (RF) ablation lesions were delivered. Ablation lesions were visualized in real time during RF delivery using MR-thermometry and dosimetry. Hyper-acute and acute assessment of ablation lesions was also performed using native T1 mapping and late-gadolinium enhancement (LGE), respectively. High-quality epicardial bipolar electrograms were recorded with a signal-to-noise ratio of greater than 10:1 for a signal of 1.5 mV. During epicardial ablation, localized temperature elevation could be visualized with a maximum temperature rise of 35 °C within 2 mm of the catheter tip relative to remote myocardium. Decreased native T1 times were observed (882 ± 107 ms) in the lesion core 3-5 min after lesion delivery and relative location of lesions matched well to LGE. There was a good correlation between ablation lesion site on the iCMR platform and autopsy. Conclusion: The MR-EP system was able to successfully acquire epicardial voltage and activation maps in swine, deliver, and visualize ablation lesions, demonstrating feasibility for intraprocedural guidance and real-time assessment of ablation injury.

Voltage and pace-capture mapping of linear ablation lesions overestimates chronic ablation gap size.

Aims: Conducting gaps in lesion sets are a major reason for failure of ablation procedures. Voltage mapping and pace-capture have been proposed for intra-procedural identification of gaps. We aimed to compare gap size measured acutely and chronically post-ablation to macroscopic gap size in a porcine model. Methods and results: Intercaval linear ablation was performed in eight Göttingen minipigs with a deliberate gap of ∼5 mm left in the ablation line. Gap size was measured by interpolating ablation contact force values between ablation tags and thresholding at a low force cut-off of 5 g. Bipolar voltage mapping and pace-capture mapping along the length of the line were performed immediately, and at 2 months, post-ablation. Animals were euthanized and gap sizes were measured macroscopically. Voltage thresholds to define scar were determined by receiver operating characteristic analysis as <0.56 mV (acutely) and <0.62 mV (chronically). Taking the macroscopic gap size as gold standard, error in gap measurements were determined for voltage, pace-capture, and ablation contact force maps. All modalities overestimated chronic gap size, by 1.4 ± 2.0 mm (ablation contact force map), 5.1 ± 3.4 mm (pace-capture), and 9.5 ± 3.8 mm (voltage mapping). Error on ablation contact force map gap measurements were significantly less than for voltage mapping (P = 0.003, Tukey's multiple comparisons test). Chronically, voltage mapping and pace-capture mapping overestimated macroscopic gap size by 11.9 ± 3.7 and 9.8 ± 3.5 mm, respectively. Conclusion: Bipolar voltage and pace-capture mapping overestimate the size of chronic gap formation in linear ablation lesions. The most accurate estimation of chronic gap size was achieved by analysis of catheter-myocardium contact force during ablation.

The effect of activation rate on left atrial bipolar voltage in patients with paroxysmal atrial fibrillation.

INTRODUCTION: Bipolar voltage is used during electroanatomic mapping to define abnormal myocardium, but the effect of activation rate on bipolar voltage is not known. We hypothesized that bipolar voltage may change in response to activation rate. By examining corresponding unipolar signals we sought to determine the mechanisms of such changes. METHODS AND RESULTS: LA extrastimulus mapping was performed during CS pacing in 10 patients undergoing first time paroxysmal atrial fibrillation ablation. Bipolar and unipolar electrograms were recorded using a PentaRay catheter (4-4-4 spacing) and indifferent IVC electrode, respectively. An S1S2 pacing protocol was delivered with extrastimulus coupling interval reducing from 350 to 200 milliseconds. At each recording site (119 ± 37 per LA), bipolar peak-to-peak voltage, unipolar peak to peak voltage and activation delay between unipole pairs was measured. Four patterns of bipolar voltage/extrastimulus coupling interval curves were seen: voltage attenuation with plateau voltage >1 mV (48 ± 15%) or <1 mV (22 ± 15%), and voltage unaffected by coupling interval with plateau voltage >1 mV (17 ± 10%) or <1 mV (13 ± 8%). Electrograms showing bipolar voltage attenuation were associated with significantly greater unipolar voltage attenuation at low (25 ± 28 mV/s vs. 9 ± 11 mV/s) and high (23 ± 29 mV/s vs. 6 ± 12 mV/s) plateau voltage sites (P < 0.001). There was a small but significant increase in conduction delay between unipole pairs at sites showing bipolar voltage attenuation (P = 0.026). CONCLUSIONS: Bipolar electrogram voltage is dependent on activation rate at a significant proportion of sites. Changes in unipolar voltage and timing underlie these effects. These observations have important implications for use of voltage mapping to delineate abnormal atrial substrate.

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial.

Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results: A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration: clinicaltrials.gov Identifier: NCT00990132.

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure.

BACKGROUND AND OBJECTIVE: We sought to elicit predictors of in-hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward-based non-invasive ventilation (NIV), and identify features associated with long-term survival. METHODS: Analysis of prospectively collected data at a single centre on patients undergoing NIV for AHRF between 2004 and 2009. Predictors of in-hospital mortality and intubation were sought by logistic regression and predictors of long-term survival by Cox regression. RESULTS: Initial pH exhibited a threshold effect for in-hospital mortality at pH 7.15. This relationship remained in patients undergoing their first episode of AHRF. In both first and subsequent admissions, a pH threshold of 7.25 at 4 h was associated with better prognosis (P = 0.02 and P = 0.04 respectively). In second or subsequent episodes of AHRF, mortality was lower and predicted only by age (P = 0.002) on multivariate analysis. CONCLUSIONS: NIV could be used on medical wards for patients with pH 7.16 or greater on their first admission, although more conservative values should continue to be used for those with a second or subsequent episodes of AHRF.

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.

Comorbidity Profiling in Rural and Urban Population of West Bengal, India: Report From a Community-Based Primary Healthcare System.

Introduction The burden of non-communicable diseases (NCDs) is fast changing across the world, especially in the context of rapid urbanization, adoption of Western lifestyles, and an aging multi-morbid population. Over the last three decades, India has undergone a significant demographic and socioeconomic transition. For effective targeting of health system resources and services, it is essential to understand how the prevalence of NCDs varies among population groups across India. We set out to understand the distribution of NCDs and co-morbidities in urban and rural West Bengal. Methods As part of a service improvement project, data was collected from four urban and four rural community-based clinics across West Bengal, India. The reason for visiting the healthcare center was recorded as the primary diagnosis and co-morbidities were recorded per the Elixhauser comorbidity scoring criteria. Associations between all the demographic variables and NCDs were studied using the Poisson regression model and multivariate analysis. Demographic profile, co-morbidities, and Elixhauser comorbidity index were expressed as frequency (%), mean (standard deviation, SD), or median (interquartile range, IQR) as appropriate. Results We obtained data from 1244 patients of which 886 (71%) were from urban areas and 358 (29%) were from rural areas. Patients were mostly female (61%) and had a mean (SD) age of 53 (11) years. There was a positive correlation between living in an urban residence and age, body mass index (BMI), hypertension, cardiovascular disease (CVD), and respiratory disease. There was a positive correlation between CVD and age, male sex, living in an urban residence, and hypertension but did not correlate positively with diabetes. BMI positively correlated with living in an urban residence, hypertension, diabetes, and musculoskeletal disorders. We observed a significantly higher prevalence of musculoskeletal (p=0.002) and psychological diseases (p<0.001) in the rural population, while the prevalence of hypertension (p<0.001) and respiratory diseases among the participants living in urban areas was higher (p<0.001). There was no statistically significant difference in the prevalence of diabetes between urban and rural areas (p=0.38). In the multivariable analyses, we observed that increased age, being overweight, and living in urban areas were associated with hypertension (prevalence ratio (PR): 1.40, 1.30, and 1.30, respectively; all p-values <0.05). An interaction between sex and living area was associated with a lower prevalence of musculoskeletal diseases (PR: 0.34; 95%CI: 0.18-0.66), i.e., musculoskeletal diseases were less prevalent in males living in urban areas (p=0.002). Conclusion There is a rise in multimorbidity with changing demographic patterns and a narrowing of the urban-rural gap in disease distribution. More investment is required in risk factor prevention, screening, and treatment, with greater accessibility of healthcare resources for those in rural areas. Further work needs to be done to study the trends and distribution of NCDs in West Bengal to inform healthcare policy.