Computerized surgical navigation resection of pelvic region simulated bone tumors using skin fiducial marker registration: an in vitro cadaveric study.

INTRODUCTION: Computerized surgical navigation system guidance can improve bone tumor surgical resection accuracy. This study compared the 10-mm planned resection margin agreement between simulated pelvic-region bone tumors (SPBT) resected using either skin fiducial markers or Kirschner (K)-wires inserted directly into osseous landmarks with navigational system registration under direct observation. We hypothesized that skin fiducial markers would display similar resection margin accuracy. METHODS: Six cadaveric pelvises had one SPBT implanted into each supra-acetabular region. At the left hemi-pelvis, the skin fiducial marker group had guidance from markers placed over the pubic tubercle, the anterior superior iliac spine, the central and more posterior iliac crest, and the greater trochanter (5 markers). At the right hemi-pelvis, the K-wire group had guidance from 1.4-mm-diameter wires inserted into the pubic tubercle, and 3 inserted along the iliac crest (4 K-wires). The senior author, a fellowship-trained surgeon performed "en bloc" SPBT resections. The primary investigator, blinded to group assignment, measured actual resection margins. RESULTS: Twenty of 22 resection margins (91%) in the skin fiducial marker group were within the Bland-Altman plot 95% confidence interval for actual-planned margin mean difference (mean = -0.23 mm; 95% confidence intervals = 2.8 mm, - 3.3 mm). Twenty-one of 22 resection margins (95%) in the K-wire group were within the 95% confidence interval of actual-planned margin mean difference (mean = 0.26 mm; 95% confidence intervals = 1.7 mm, - 1.1 mm). CONCLUSION: Pelvic bone tumor resection with navigational guidance from skin fiducial markers placed over osseous landmarks provided similar accuracy to K-wires inserted into osseous landmarks. Further in vitro studies with different SPBT dimensions/locations and clinical studies will better delineate use efficacy.

Understanding the health system utilisation and reasons for avoidable mortality after fatal injury within a Three-Delays framework in Karonga, Northern Malawi: a retrospective analysis of verbal autopsy data.

OBJECTIVES: To use verbal autopsy (VA) data to understand health system utilisation and the potential avoidability associated with fatal injury. Then to categorise any evident barriers driving avoidable delays to care within a Three-Delays framework that considers delays to seeking (Delay 1), reaching (Delay 2) or receiving (Delay 3) quality injury care. DESIGN: Retrospective analysis of existing VA data routinely collected by a demographic surveillance site. SETTING: Karonga Health and Demographic Surveillance Site (HDSS) population, Northern Malawi. PARTICIPANTS: Fatally injured members of the HDSS. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of fatal injury deaths that were potentially avoidable. Secondary outcomes were the delay stage and corresponding barriers associated with avoidable deaths and the health system utilisation for fatal injuries within the health system. RESULTS: Of the 252 deaths due to external causes, 185 injury-related deaths were analysed. Deaths were predominantly among young males (median age 30, IQR 11-48), 71.9% (133/185). 35.1% (65/185) were assessed as potentially avoidable. Delay 1 was implicated in 30.8% (20/65) of potentially avoidable deaths, Delay 2 in 61.5% (40/65) and Delay 3 in 75.4% (49/65). Within Delay 1, 'healthcare literacy' was most commonly implicated barrier in 75% (15/20). Within Delay 2, 'communication' and 'prehospital care' were the most commonly implicated in 92.5% (37/40). Within Delay 3, 'physical resources' were most commonly implicated, 85.7% (42/49). CONCLUSIONS: VA is feasible for studying pathways to care and health system responsiveness in avoidable deaths following injury and ascertaining the delays that contribute to deaths. A large proportion of injury deaths were avoidable, and we have identified several barriers as potential targets for intervention. Refining and integrating VA with other health system assessment methods is likely necessary to holistically understand an injury care health system.

Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

The development of inherited cardiac conditions services: current position and future perspectives.

BACKGROUND: Over the last two decades, inherited cardiac conditions (ICC) centres have emerged with the aim of improving outcomes for patients and their families, through early diagnosis, genetic testing, risk assessment and specialist treatment. SOURCES OF DATA: A literature search was performed using PubMed (https://pubmed.ncbi.nlm.nih.gov/). Commissioned ICC service reviews from NHS England, NHS Improvement and PHG Foundation were evaluated. AREAS OF AGREEMENT: ICC patient management requires a multi-disciplinary approach. ICC services are predominantly based within tertiary centres. Despite expansion, provision of care remains inadequate to meet rising demands. Access to services is inconsistent, partly due to geographic variation and lack of standardized pathways. AREAS OF CONTROVERSY: The optimal ICC care model remains undecided, although there is growing interest in 'hub-and-spoke' networks, which could aid secondary and tertiary service integration and repatriation of care. GROWING POINTS: Genetic mainstreaming is a priority for the Genomic Medicine Service Alliance. The benefits of telehealth and virtual clinics have been validated by their use during the COVID-19 pandemic. Other innovations to improve resource efficiency, such as clinical scientist-led and nurse-led clinics, show promise. AREAS TIMELY FOR DEVELOPING RESEARCH: An update for the NHS ICC service specifications is planned that appears well timed given the rapid evolution of the ICC landscape in the decade since last review. This has the potential to address needs including national audit, standardized pathways and ICC networks to improve governance and equity of care. Delegation of commissioning for specialist services to integrated care systems may also provide opportunity for increased regional direction.

Individual characteristics associated with road traffic collisions and healthcare seeking in low- and middle-income countries and territories.

Incidence of road traffic collisions (RTCs), types of users involved, and healthcare requirement afterwards are essential information for efficient policy making. We analysed individual-level data from nationally representative surveys conducted in low- or middle-income countries (LMICs) between 2008-2019. We describe the weighted incidence of non-fatal RTC in the past 12 months, type of road user involved, and incidence of traffic injuries requiring medical attention. Multivariable logistic regressions were done to evaluate associated sociodemographic and economic characteristics, and alcohol use. Data were included from 90,790 individuals from 15 countries or territories. The non-fatal RTC incidence in participants aged 24-65 years was 5.2% (95% CI: 4.6-5.9), with significant differences dependent on country income status. Drivers, passengers, pedestrians and cyclists composed 37.2%, 40.3%, 11.3% and 11.2% of RTCs, respectively. The distribution of road user type varied with country income status, with divers increasing and cyclists decreasing with increasing country income status. Type of road users involved in RTCs also varied by the age and sex of the person involved, with a greater proportion of males than females involved as drivers, and a reverse pattern for pedestrians. In multivariable analysis, RTC incidence was associated with younger age, male sex, being single, and having achieved higher levels of education; there was no association with alcohol use. In a sensitivity analysis including respondents aged 18-64 years, results were similar, however, there was an association of RTC incidence with alcohol use. The incidence of injuries requiring medical attention was 1.8% (1.6-2.1). In multivariable analyses, requiring medical attention was associated with younger age, male sex, and higher wealth quintile. We found remarkable heterogeneity in RTC incidence, the type of road users involved, and the requirement for medical attention after injuries depending on country income status and socio-demographic characteristics. Targeted data-informed approaches are needed to prevent and manage RTCs.

Access to quality care after injury in Northern Malawi: results of a household survey.

BACKGROUND: Most injury care research in low-income contexts such as Malawi is facility centric. Community-derived data is needed to better understand actual injury incidence, health system utilisation and barriers to seeking care following injury. METHODS: We administered a household survey to 2200 households in Karonga, Malawi. The primary outcome was injury incidence, with non-fatal injuries classified as major or minor (> 30 or 1-29 disability days respectively). Those seeking medical treatment were asked about time delays to seeking, reaching and receiving care at a facility, where they sought care, and whether they attended a second facility. We performed analysis for associations between injury severity and whether the patient sought care, stayed overnight in a facility, attended a second facility, or received care within 1 or 2 h. The reason for those not seeking care was asked. RESULTS: Most households (82.7%) completed the survey, with 29.2% reporting an injury. Overall, 611 non-fatal and four fatal injuries were reported from 531 households: an incidence of 6900 per 100,000. Major injuries accounted for 26.6%. Three quarters, 76.1% (465/611), sought medical attention. Almost all, 96.3% (448/465), seeking care attended a primary facility first. Only 29.7% (138/465), attended a second place of care. Only 32.0% (142/444), received care within one hour. A further 19.1% (85/444) received care within 2 h. Major injury was associated with being more likely to have; sought care (94.4% vs 69.8% p < 0.001), stayed overnight at a facility (22.9% vs 15.4% P = 0.047), attended a second place of care (50.3% vs 19.9%, P < 0.001). For those not seeking care the most important reason was the injury not being serious enough for 52.1% (74/142), followed by transport difficulties 13.4% (19/142) and financial costs 5.6% (8/142). CONCLUSION: Injuries in Northern Malawi are substantial. Community-derived details are necessary to fully understand injury burden and barriers to seeking and reaching care.

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.

Exploring the global health and defence engagement interface.

Militaries have an important and inevitable role in global health and will interface with existing health systems on deployments. While the primary concern of militaries is not global health, there are clear, and increasingly frequent, circumstances when global health activities align with the interests of defence. Recognising this link between global health and security warrants thoughtful consideration and action where concerns affecting both intersect. In addition to providing medical support to military personnel on operations, advantageous effects can be achieved directly from military medical activities as part of Defence Engagement. While there are limitations and ethical boundaries to the role of militaries in global health, further training, research and conceptual development are warranted to optimise military medical activity at the intersection of security and global health to deliver advantageous effects. This paper forms part of a special issue of BMJ Military Health dedicated to Defence Engagement.

Diagnosis and management of ventricular tachycardia.

Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist services for ongoing management. The diagnosis of VT is usually made based on electrocardiographic data, most commonly 12-lead echocardiography (ECG), as well as supportive cardiac telemetric monitoring. Distinguishing between VT and supraventricular arrhythmias on ECG can be difficult. However, the VT diagnosis frequently needs to be made rapidly in the acute setting. In this review, we discuss the definition of VT, review features of wide-complex tachycardia (WCT) on ECG that might be helpful in diagnosing VT, discuss the different substrates in which VT can occur and offer brief comments on management considerations for patients found to have VT.

Free Hip Arthroplasty Templating Software - Does it Work?

Background: Preoperative planning is important for successful total hip arthroplasty (THA) and has been historically performed using acetate templates. Digital software templating has been adopted for evaluating implant size, position, and alignment. Commercial software can be expensive, but free programs exist. Detroit Bone Setter (detroitbonesetter.com, Detroit, MI) is a freely available templating program, but hasn't been validated. Our study reports this program's accuracy for templating THA. Methods: Sixty-five patients undergoing THA between 2017 and 2022 at 2 hospitals were included. All cases were templated by the senior author or orthopaedic trauma fellow prospectively or retrospectively in a blinded fashion. Direct anterior or posterior approaches were used based on attending surgeon's preference. A student's t-test was used to compare means of templated vs actual implant sizes of femoral and acetabular components. Results: There was no significant difference between implanted (mean [M] = 6.4, standard deviation [SD] = 2.0) and templated femoral component sizes (M = 5.7, SD = 2.1). There was a significant difference between implanted (M = 57.0, SD = 3.9) and templated acetabular component sizes (M = 53.4, SD = 3.0). Bland-Altman testing demonstrated femoral components with positive measurement bias of 0.62, indicating slight overestimation of implant size. Acetabular component size was overestimated with positive measurement bias of 3.6 mm. Conclusions: Detroit Bone Setter is advantageous as it is freely available and supports most major company implants. It accurately templated femoral component size but consistently overestimated acetabular component size by 3.6 mm. Further studies are needed prior to recommending its routine use for templating THA when other validated methods exist. It could be used with caution when no other methods are available.

Stereotactic arrhythmia radioablation: A multicenter pre-post intervention safety evaluation of the implantable cardioverter-defibrillator function.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) appears to be beneficial in selected patients with therapy-refractory ventricular tachycardia (VT). However, high-dose radiotherapy used for STAR-treatment may affect functioning of the patients' implantable cardioverter defibrillator (ICD) by direct effects of radiation on ICD components or cardiac tissue. Currently, the effect of STAR on ICD functioning remains unknown. METHODS: A retrospective pre-post multicenter study evaluating ICD functioning in the 12-month before and after STAR was performed. Patients with (non)ischemic cardiomyopathies with therapy-refractory VT and ICD who underwent STAR were included and the occurrence of ICD-related adverse events was collected. Evaluated ICD parameters included sensing, capture threshold and impedance. A linear mixed-effects model was used to investigate the association between STAR, radiotherapy dose and changes in lead parameters over time. RESULTS: In total, 43 patients (88% male) were included in this study. All patients had an ICD with an additional right atrial lead in 34 (79%) and a ventricular lead in 17 (40%) patients. Median ICD-generator dose was 0.1 Gy and lead tip dose ranged from 0-32 Gy. In one patient (2%), a reset occurred during treatment, but otherwise, STAR and radiotherapy dose were not associated with clinically relevant alterations in ICD leads parameters. CONCLUSIONS: STAR treatment did not result in major ICD malfunction. Only one radiotherapy related adverse event occurred during the study follow-up without patient harm. No clinically relevant alterations in ICD functioning were observed after STAR in any of the leads. With the reported doses STAR appears to be safe.

Gender Diversity in Sports Medicine: Current Trends.

As the sports medicine field has grown, the need for a more diverse workforce has become more evident. Given the growing athlete diversity that exists at all recreational and competitive levels of organized sports, it is important to better understand the current state of athletic health care diversity. This review assesses the current state of diversity in sports medicine from the perspective of the medical and athletic training professions. Men and women currently display nearly equivalent participation levels; however, the distribution of female team physicians and athletic trainers could better match the teams that they serve. Although progress has been made, much more needs to be done to bring more female athletic trainers and team physicians into athletic health care leadership roles. Early mentoring programs have shown efficacy for increasing the number of female candidates who might become the foundation of future athletic health care and academic program leaders. Level of Evidence: V, expert opinion.

Novel application of multi-facility process map analysis for rapid injury care health system assessment in Northern Malawi.

OBJECTIVES: We used the process mapping method and Three Delays framework, to identify and visually represent the relationship between critical actions, decisions and barriers to access to care following injury in the Karonga health system, Northern Malawi. DESIGN: Facilitated group process mapping workshops with summary process mapping synthesis. SETTING: Process mapping workshops took place in 11 identified health system facilities (one per facility) providing injury care for a population in Karonga, Northern Malawi. PARTICIPANTS: Fifty-four healthcare workers from various cadres took part. RESULTS: An overall injury health system summary map was created using those categories of action, decision and barrier that were sometimes or frequently reported. This provided a visual summary of the process following injury within the health system. For Delay 1 (seeking care) four barriers were most commonly described (by 8 of 11 facilities) these were 'cultural norms', 'healthcare literacy', 'traditional healers' and 'police processes'. For Delay 2 (reaching care) the barrier most frequently described was 'transport'-a lack of timely affordable emergency transport (formal or informal) described by all 11 facilities. For Delay 3 (receiving quality care) the most commonly reported barrier was that of 'physical resources' (9 of 11 facilities). CONCLUSIONS: We found our novel approach combining several process mapping exercises to produce a summary map to be highly suited to rapid health system assessment identifying barriers to injury care, within a Three Delays framework. We commend the approach to others wishing to conduct rapid health system assessments in similar contexts.

Additional coils mitigate elevated defibrillation threshold in right-sided implantable cardioverter defibrillator generator placement: a simulation study.

AIMS: The standard implantable cardioverter defibrillator (ICD) generator (can) is placed in the left pectoral area; however, in certain circumstances, right-sided cans may be required which may increase defibrillation threshold (DFT) due to suboptimal shock vectors. We aim to quantitatively assess whether the potential increase in DFT of right-sided can configurations may be mitigated by alternate positioning of the right ventricular (RV) shocking coil or adding coils in the superior vena cava (SVC) and coronary sinus (CS). METHODS AND RESULTS: A cohort of CT-derived torso models was used to assess DFT of ICD configurations with right-sided cans and alternate positioning of RV shock coils. Efficacy changes with additional coils in the SVC and CS were evaluated. A right-sided can with an apical RV shock coil significantly increased DFT compared to a left-sided can [19.5 (16.4, 27.1) J vs. 13.3 (11.7, 19.9) J, P < 0.001]. Septal positioning of the RV coil led to a further DFT increase when using a right-sided can [26.7 (18.1, 36.1) J vs. 19.5 (16.4, 27.1) J, P < 0.001], but not a left-sided can [12.1 (8.1, 17.6) J vs. 13.3 (11.7, 19.9) J, P = 0.099). Defibrillation threshold of a right-sided can with apical or septal coil was reduced the most by adding both SVC and CS coils [19.5 (16.4, 27.1) J vs. 6.6 (3.9, 9.9) J, P < 0.001, and 26.7 (18.1, 36.1) J vs. 12.1 (5.7, 13.5) J, P < 0.001]. CONCLUSION: Right-sided, compared to left-sided, can positioning results in a 50% increase in DFT. For right-sided cans, apical shock coil positioning produces a lower DFT than septal positions. Elevated right-sided can DFTs may be mitigated by utilizing additional coils in SVC and CS.

Non-Invasive Diagnosis of Sun Damaged Skin: Actinic Keratosis Vs Squamous Cell Carcinoma.

IMPORTANCE: Actinic keratosis (AK) is a premalignant lesion that has a1% to 10% potential of progression to squamous cell carcinoma (SCC), but it is not possible to determine which lesions are at higher risk. OBJECTIVE: This study examined the epidermal genetic profiles of actinic keratosis and SCC through non-invasive techniques seeking to develop a biopsy-free method for AK monitoring and aid in the early diagnosis of developing SCC. DESIGN: Ribonucleic acid (RNA) was collected from adhesive tape strips and gene expression levels were measured. A threshold fold change >2 and adjusted P-value <0.05 were used to determine differentially expressed genes. SETTING: Single center dermatology clinic. PARTICIPANTS: Patients who presented to the clinic with lesions suspicious of non-melanoma skin cancer that had never been previously biopsied. MAIN OUTCOME AND MEASURE: RNA was extracted via non-invasive biopsy and sequenced. Low quality samples were filtered out and the remaining samples underwent differential gene expression analysis by DESeq2 in R package. A threshold of fold change >2 and adjusted P-value <0.05 was used for determination of differentially expressed genes. The differentially expressed genes that overlapped between the corrected and uncorrected groups were the most significant for analysis. RESULTS: From 47 lesions, 6 significant differentially expressed genes were found between AK and SCC, and 25 significant differentially expressed genes between in-situ SCC and invasive SCC. Individual samples showed similarities based on diagnosis, suggesting mutations were specific to the disease and not the individual. CONCLUSIONS AND RELEVANCE: These findings highlight which genes may play a role in AK progression to SCC. The genomic differences between in-situ and invasive squamous cell carcinoma open an opportunity for early diagnosis of squamous cell carcinoma and risk prediction of actinic keratosis. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7097.

Surveillance Post Surgery for Retroperitoneal Soft Tissue Sarcoma.

Complete en bloc surgical resection offers the best opportunity for the cure of primary retroperitoneal sarcomas (RPS). The potential for disease recurrence, in the form of both loco-regional recurrence and distant metastases, underpins the rationale for postoperative surveillance. There is a paucity of high-quality evidence underpinning follow-up for RPS patients, and most practice guidelines draw from expert opinion and evidence from soft tissue sarcomas of the extremities. The available observational retrospective data analysis has failed to demonstrate that high-intensity radiological surveillance improves the overall survival in patients. The lack of a robust evidence base has given rise to variations in approaches to post-operative surveillance strategies adopted by specialist centres managing RPS across the world. More high-quality prospective research is needed and planned to more clearly support surveillance approaches that balance oncologic outcomes, patient-centric care, and health service value. Risk stratification tools exist and are available for use in routine practice. Their use will likely support more individualised post-operative surveillance moving forward. Surveillance will likely be underpinned by serial radiological imaging for the medium term. However, developments in genomics offer hope for biomarkers such as ctDNA to impact patient care positively in the future and further support individualised patient care pathways.

Frequency Domain Analysis of Endocardial Electrograms for Detection of Nontransmural Myocardial Fibrosis in Nonischemic Cardiomyopathy.

BACKGROUND: Voltage mapping in nonischemic cardiomyopathy can fail to identify midmyocardial substrate for ventricular arrhythmias, an important cause of ablation failure. OBJECTIVES: The aim of this study was to assess whether frequency domain analysis of endocardial left ventricular electrograms (EGMs) can better predict the presence of midmyocardial fibrosis (MMF) compared with voltage amplitude. METHODS: Nonischemic cardiomyopathy patients undergoing ventricular tachycardia ablation with registered preprocedural cardiac computed tomography and late iodine enhancement were included. Presence of fibrosis at each EGM site was assessed. Bipolar and unipolar EGMs were transformed to the frequency domain using multitaper spectral analysis. Singular value decomposition of the EGM frequency spectrum was used within a supervised machine learning process to select features to predict the presence of MMF and compare against predictions using voltage amplitude. RESULTS: Thirteen patients were included (median age 57 years [IQR: 28-73 years], median ejection fraction 40% [IQR: 15%-57%]). A total of 6,015 EGM pairs were processed: 2,459 EGM pairs in MMF areas and 3,556 EGM pairs in non-MMF areas. Supervised classifiers were trained with stratified k-fold cross-validation within patients. The distribution of mean area under the curve metrics using frequency features, f, was significantly greater than voltage feature area under the curve metrics, v, (mean f = 0.841 [95% CI: 0.789-0.884] vs mean v = 0.591 [95% CI: 0.530-0.658]; P < 0.001), indicating that frequency-trained classifiers better predicted the presence of MMF. CONCLUSIONS: These data indicate the promising discriminatory value of endocardial EGM frequency content in the assessment of concealed myocardial substrate. Further studies are needed to investigate the importance of the specific frequency features identified.

Assessing the arrhythmogenic risk of engineered heart tissue patches through in silico application on infarcted ventricle models.

BACKGROUND: Post myocardial infarction (MI) ventricles contain fibrotic tissue and may have disrupted electrical properties, both of which predispose to an increased risk of life-threatening arrhythmias. Application of epicardial patches obtained from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a potential long-term therapy to treat heart failure resulting from post MI remodelling. However, whether the introduction of these patches is anti- or pro-arrhythmic has not been studied. METHODS: We studied arrhythmic risk using in silico engineered heart tissue (EHT) patch engraftment on human post-MI ventricular models. Two patient models were studied, including one with a large dense scar and one with an apparent channel of preserved viability bordered on both sides by scar. In each heart model a virtual EHT patch was introduced as a layer of viable tissue overlying the scarred area, with hiPSC-CMs electrophysiological properties. The incidence of re-entrant and sustained activation in simulations with and without EHT patches was assessed and the arrhythmia inducibility compared in the context of different EHT patch properties (conduction velocity (CV) and action potential duration (APD)). The impact of the EHT patch on the likelihood of focal ectopic impulse propagation was estimated by assessing the minimum stimulus strength and duration required to generate a propagating impulse in the scar border zone (BZ) with and without patch. RESULTS: We uncovered two main mechanisms by which ventricular tachycardia (VT) risk could be either augmented or attenuated by the interaction of the patch with the tissue. In the case of isthmus-related VT, our simulations predict that EHT patches can prevent the induction of VT when the, generally longer, hiPSC-CMs APD is reduced towards more physiological values. In the case of large dense scar, we found that, an EHT patch with CV similar to the host myocardium does not promote VT, while EHT patches with lower CV increase the risk of VT, by promoting both non-sustained and sustained re-entry. Finally, our simulations indicate that electrically coupled EHT patches reduce the likelihood of propagation of focal ectopic impulses. CONCLUSIONS: The introduction of EHT patches as a treatment for heart failure has the potential to augment or attenuate the risk of ventricular arrhythmias, and variations in the anatomic configuration of the substrate, the functional properties of the BZ and the electrophysiologic properties of the patch itself will determine the overall impact. Planning for delivery of this therapy will need to consider the possible impact on arrhythmia.