Health system assessment for access to care after injury in low- or middle-income countries: A mixed methods study from Northern Malawi.

BACKGROUND: Injuries represent a vast and relatively neglected burden of disease affecting low- and middle-income countries (LMICs). While many health systems underperform in treating injured patients, most assessments have not considered the whole system. We integrated findings from 9 methods using a 3 delays approach (delays in seeking, reaching, or receiving care) to prioritise important trauma care health system barriers in Karonga, Northern Malawi, and exemplify a holistic health system assessment approach applicable in comparable settings. METHODS AND FINDINGS: To provide multiple perspectives on each conceptual delay and include data from community-based and facility-based sources, we used 9 methods to examine the injury care health system. The methods were (1) household survey; (2) verbal autopsy analysis; (3) community focus group discussions (FGDs); (4) community photovoice; (5) facility care-pathway process mapping and elucidation of barriers following injury; (6) facility healthcare worker survey; (7) facility assessment survey; (8) clinical vignettes for care process quality assessment of facility-based healthcare workers; and (9) geographic information system (GIS) analysis. Empirical data collection took place in Karonga, Northern Malawi, between July 2019 and February 2020. We used a convergent parallel study design concurrently conducting all data collection before subsequently integrating results for interpretation. For each delay, a matrix was created to juxtapose method-specific data relevant to each barrier identified as driving delays to injury care. Using a consensus approach, we graded the evidence from each method as to whether an identified barrier was important within the health system. We identified 26 barriers to access timely quality injury care evidenced by at least 3 of the 9 study methods. There were 10 barriers at delay 1, 6 at delay 2, and 10 at delay 3. We found that the barriers "cost," "transport," and "physical resources" had the most methods providing strong evidence they were important health system barriers within delays 1 (seeking care), 2 (reaching care), and 3 (receiving care), respectively. Facility process mapping provided evidence for the greatest number of barriers-25 of 26 within the integrated analysis. There were some barriers with notable divergent findings between the community- and facility-based methods, as well as among different community- and facility-based methods, which are discussed. The main limitation of our study is that the framework for grading evidence strength for important health system barriers across the 9 studies was done by author-derived consensus; other researchers might have created a different framework. CONCLUSIONS: By integrating 9 different methods, including qualitative, quantitative, community-, patient-, and healthcare worker-derived data sources, we gained a rich insight into the functioning of this health system's ability to provide injury care. This approach allowed more holistic appraisal of this health system's issues by establishing convergence of evidence across the diverse methods used that the barriers of cost, transport, and physical resources were the most important health system barriers driving delays to seeking, reaching, and receiving injury care, respectively. This offers direction and confidence, over and above that derived from single methodology studies, for prioritising barriers to address through health service development and policy.

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.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

Equitable access to quality trauma systems in low-income and middle-income countries: assessing gaps and developing priorities in Ghana, Rwanda and South Africa.

Injuries in low-income and middle-income countries are prevalent and their number is expected to increase. Death and disability after injury can be reduced if people reach healthcare facilities in a timely manner. Knowledge of barriers to access to quality injury care is necessary to intervene to improve outcomes. We combined a four-delay framework with WHO Building Blocks and Institution of Medicine Quality Outcomes Frameworks to describe barriers to trauma care in three countries in sub-Saharan Africa: Ghana, South Africa and Rwanda. We used a parallel convergent mixed-methods research design, integrating the results to enable a holistic analysis of the barriers to access to quality injury care. Data were collected using surveys of patient experiences of injury care, interviews and focus group discussions with patients and community leaders, and a survey of policy-makers and healthcare leaders on the governance context for injury care. We identified 121 barriers across all three countries. Of these, 31 (25.6%) were shared across countries. More than half (18/31, 58%) were predominantly related to delay 3 ('Delays to receiving quality care'). The majority of the barriers were captured using just one of the multiple methods, emphasising the need to use multiple methods to identify all barriers. Given there are many barriers to access to quality care for people who have been injured in Rwanda, Ghana and South Africa, but few of these are shared across countries, solutions to overcome these barriers may also be contextually dependent. This suggests the need for rigorous assessments of contexts using multiple data collection methods before developing interventions to improve access to quality care.

An in-silico assessment of efficacy of two novel intra-cardiac electrode configurations versus traditional anti-tachycardia pacing therapy for terminating sustained ventricular tachycardia.

The implanted cardioverter defibrillator (ICD) is an effective direct therapy for the treatment of cardiac arrhythmias, including ventricular tachycardia (VT). Anti-tachycardia pacing (ATP) is often applied by the ICD as the first mode of therapy, but is often found to be ineffective, particularly for fast VTs. In such cases, strong, painful and damaging backup defibrillation shocks are applied by the device. Here, we propose two novel electrode configurations: "bipolar" and "transmural" which both combine the concept of targeted shock delivery with the advantage of reduced energy required for VT termination. We perform an in silico study to evaluate the efficacy of VT termination by applying one single (low-energy) monophasic shock from each novel configuration, comparing with conventional ATP therapy. Both bipolar and transmural configurations are able to achieve a higher efficacy (93% and 85%) than ATP (45%), with energy delivered similar to and two orders of magnitudes smaller than conventional ICD defibrillation shocks, respectively. Specifically, the transmural configuration (which applies the shock vector directly across the scar substrate sustaining the VT) is most efficient, requiring typically less than 1 J shock energy to achieve a high efficacy. The efficacy of both bipolar and transmural configurations are higher when applied to slow VTs (100% and 97%) compared to fast VTs (57% and 29%). Both novel electrode configurations introduced are able to improve electrotherapy efficacy while reducing the overall number of required therapies and need for strong backup shocks.

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.

Local Conduction Velocity in the Presence of Late Gadolinium Enhancement and Myocardial Wall Thinning: A Cardiac Magnetic Resonance Study in a Swine Model of Healed Left Ventricular Infarction.

BACKGROUND: Conduction velocity (CV) is an important property that contributes to the arrhythmogenicity of the tissue substrate. The aim of this study was to investigate the association between local CV versus late gadolinium enhancement (LGE) and myocardial wall thickness in a swine model of healed left ventricular infarction. METHODS: Six swine with healed myocardial infarction underwent cardiovascular magnetic resonance imaging and electroanatomic mapping. Two healthy controls (one treated with amiodarone and one unmedicated) underwent electroanatomic mapping with identical protocols to establish the baseline CV. CV was estimated using a triangulation technique. LGE+ regions were defined as signal intensity >2 SD than the mean of remote regions, wall thinning+ as those with wall thickness <2 SD than the mean of remote regions. LGE heterogeneity was defined as SD of LGE in the local neighborhood of 5 mm and wall thickness gradient as SD within 5 mm. Cardiovascular magnetic resonance and electroanatomic mapping data were registered, and hierarchical modeling was performed to estimate the mean difference of CV (LGE+/-, wall thinning+/-), or the change of the mean of CV per unit change (LGE heterogeneity, wall thickness gradient). RESULTS: Significantly slower CV was observed in LGE+ (0.33±0.25 versus 0.54±0.36 m/s; P<0.001) and wall thinning+ regions (0.38±0.28 versus 0.55±0.37 m/s; P<0.001). Areas with greater LGE heterogeneity ( P<0.001) and wall thickness gradient ( P<0.001) exhibited slower CV. CONCLUSIONS: Slower CV is observed in the presence of LGE, myocardial wall thinning, high LGE heterogeneity, and a high wall thickness gradient. Cardiovascular magnetic resonance may offer a valuable imaging surrogate for estimating CV, which may support noninvasive identification of the arrhythmogenic substrate.

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.

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.

Local activation time sampling density for atrial tachycardia contact mapping: how much is enough?

Aims: Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach. Methods and results: In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry. In silico activation was simulated on a 4×4cm atrial monolayer, sampled randomly at 0.25-10 points/cm2 and used to re-interpolate LAT maps. Activation patterns were studied in the geometrically simple porcine right atrium (RA) and complex human left atrium (LA). Activation complexity was introduced into the porcine RA by incomplete inter-caval linear ablation. In all cases, optimal sampling density was defined as the highest density resulting in minimal further error reduction in the re-interpolated maps. Optimal sampling densities for LA tachycardias were 0.67 ± 0.17 points/cm2 (focal activation), 1.05 ± 0.32 points/cm2 (macro-re-entry) and 1.23 ± 0.26 points/cm2 (localized re-entry), P = 0.0031. Increasing activation complexity was associated with increased optimal sampling density both in silico (focal activation 1.09 ± 0.14 points/cm2; re-entry 1.44 ± 0.49 points/cm2; spiral-wave 1.50 ± 0.34 points/cm2, P < 0.0001) and in vivo (porcine RA pre-ablation 0.45 ± 0.13 vs. post-ablation 0.78 ± 0.17 points/cm2, P = 0.0008). Increasing chamber geometry was also associated with increased optimal sampling density (0.61 ± 0.22 points/cm2 vs. 1.0 ± 0.34 points/cm2, P = 0.0015). Conclusion: Optimal sampling densities can be identified to maximize diagnostic yield of LAT maps. Greater sampling density is required to correctly reveal complex activation and represent activation across complex geometries. Overall, the optimal sampling density for LAT map interpolation defined in this study was ∼1.0-1.5 points/cm2.

Personalized Models of Human Atrial Electrophysiology Derived From Endocardial Electrograms.

OBJECTIVE: Computational models represent a novel framework for understanding the mechanisms behind atrial fibrillation (AF) and offer a pathway for personalizing and optimizing treatment. The characterization of local electrophysiological properties across the atria during procedures remains a challenge. The aim of this work is to characterize the regional properties of the human atrium from multielectrode catheter measurements. METHODS: We propose a novel method that characterizes regional electrophysiology properties by fitting parameters of an ionic model to conduction velocity and effective refractory period restitution curves obtained by a s1-s2 pacing protocol applied through a multielectrode catheter. Using an in-silico dataset we demonstrate that the fitting method can constrain parameters with a mean error of 21.9 ± 16.1% and can replicate conduction velocity and effective refractory curves not used in the original fitting with a relative error of 4.4 ± 6.9%. RESULTS: We demonstrate this parameter estimation approach on five clinical datasets recorded from AF patients. Recordings and parametrization took approx. 5 and 6 min, respectively. Models fitted restitution curves with an error of ~ 5% and identify a unique parameter set. Tissue properties were predicted using a two-dimensional atrial tissue sheet model. Spiral wave stability in each case was predicted using tissue simulations, identifying distinct stable (2/5), meandering and breaking up (2/5), and unstable self-terminating (1/5) spiral tip patterns for different cases. CONCLUSION AND SIGNIFICANCE: We have developed and demonstrated a robust and rapid approach for personalizing local ionic models from a clinically tractable.

High-Resolution Mapping of Ventricular Scar: Evaluation of a Novel Integrated Multielectrode Mapping and Ablation Catheter.

OBJECTIVES: This study sought to evaluate an investigational catheter that incorporates 3 microelectrodes embedded along the circumference of a standard 3.5-mm open-irrigated catheter. BACKGROUND: Mapping resolution is influenced by both electrode size and interelectrode spacing. Multielectrode mapping catheters enhance mapping resolution within scar compared with standard ablation catheters; however, this requires the use of 2 separate catheters for mapping and ablation. METHODS: Six swine with healed infarction and 2 healthy controls underwent mapping of the left ventricle using a THERMOCOOL SMARTTOUCH SF catheter with 3 additional microelectrodes (0.167 mm2) along its circumference (Qdot, Biosense Webster, Diamond Bar, California). Mapping resolution in healthy and scarred tissue was compared between the standard electrodes and microelectrodes using electrogram characteristics, cardiac magnetic resonance, and histology. RESULTS: In healthy myocardium, bipolar voltage amplitude was similar between the standard electrodes and microelectrodes, with a fifth percentile of 1.19 and 1.30 mV, respectively. In healed infarction, the area of low bipolar voltage (defined as <1.5 mV) was smaller with microelectrodes (16.8 cm2 vs. 25.3 cm2; p = 0.033). Specifically, the microelectrodes detected zones of increased bipolar voltage amplitude, with normal electrogram characteristics occurring at the end of or after the QRS, consistent with channels of preserved subendocardium. Identification of surviving subendocardium by the microelectrodes was consistent with cardiac magnetic resonance and histology. The microelectrodes also improved distinction between near-field and far-field electrograms, with more precise identification of scar border zones. CONCLUSIONS: This novel catheter combines high-resolution mapping and radiofrequency ablation with an open-irrigated, tissue contact-sensing technology. It improves scar mapping resolution while limiting the need for and cost associated with the use of a separate mapping catheter.

Electroanatomic Mapping and Transoesophageal Echocardiography for near Zero Fluoroscopy during Complex Left Atrial Ablation.

BACKGROUND: We evaluated Carto 3, transoesophageal echocardiography (TOE) and contact force (CF) sensing catheter in atrial fibrillation (AF) ablation. METHODS: Unselected consecutive ablations performed under general anaesthesia (GA) were studied with modified protocol (cases, n=11) and compared to retrospective consecutive controls (n=10). Patent foramen ovale (PFO) or single transseptal puncture enabled left atrial (LA) access; ablation strategy was stepwise approach. Modified protocol utilised right atrial (RA) electrograms, CF and TOE to localise SmartTouch and create RA and CS electroanatomic map (EAM) without fluoroscopy. Transseptal puncture was performed with fluoroscopy in absence of PFO. Fluoroless pulmonary vein and LA EAM was created using TOE to locate circular-mapping catheter. RESULTS: Mean age of cases was 57±11 years with 64% male compared with 60±11 (70% male) for controls. Patent foramen ovale was identified in four cases (36%) and two controls (20%). No early complications occurred. Shorter fluoroscopy time (median 36 vs 390seconds; p=0.038) and trend to lower radiation dose (median 17 vs 165 cGym2; p=0.053) was seen in cases, with no increase in total procedure time (p=0.438). CONCLUSIONS: General anaesthesia, TOE and CF mapping catheters facilitate minimised fluoroscopy for catheter ablation of LA arrhythmias. Zero fluoroscopy is possible in a majority of cases with PFO.