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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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Context: Somatic EPAS1 variants account for 5% to 8% of all pheochromocytoma and paragangliomas (PPGL) but are detected in over 90% of PPGL in patients with congenital cyanotic heart disease, where hypoxemia may select for EPAS1 gain-of-function variants. Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with chronic hypoxia and there are isolated reports of PPGL in patients with SCD, but a genetic link between the conditions has yet to be established., Objective: To determine the phenotype and EPAS1 variant status of patients with PPGL and SCD., Methods: Records of 128 patients with PPGL under follow-up at our center from January 2017 to December 2022 were screened for SCD diagnosis. For identified patients, clinical data and biological specimens were obtained, including tumor, adjacent non-tumor tissue and peripheral blood. Sanger sequencing of exons 9 and 12 of EPAS1, followed by amplicon next-generation sequencing of identified variants was performed on all samples., Results: Four patients with both PPGL and SCD were identified. Median age at PPGL diagnosis was 28 years. Three tumors were abdominal paragangliomas and 1 was a pheochromocytoma. No germline pathogenic variants in PPGL-susceptibility genes were identified in the cohort. Genetic testing of tumor tissue detected unique EPAS1 variants in all 4 patients. Variants were not detected in the germline, and 1 variant was detected in lymph node tissue of a patient with metastatic disease., Conclusion: We propose that somatic EPAS1 variants may be acquired through exposure to chronic hypoxia in SCD and drive PPGL development. Future work is needed to further characterize this association., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Aims: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic obstruction of the left ventricular (LV) outflow tract (LVOT). Although this may be mediated by interplay between the hypertrophied septal wall, systolic anterior motion of the mitral valve, and papillary muscle abnormalities, the mechanistic role of LV shape is still not fully understood. This study sought to identify the LV end-diastolic morphology underpinning oHCM., Methods and Results: Cardiovascular magnetic resonance images from 2398 HCM individuals were obtained as part of the NHLBI HCM Registry. Three-dimensional LV models were constructed and used, together with a principal component analysis, to build a statistical shape model capturing shape variations. A set of linear discriminant axes were built to define and quantify (Z-scores) the characteristic LV morphology associated with LVOT obstruction (LVOTO) under different physiological conditions and the relationship between LV phenotype and genotype. The LV remodelling pattern in oHCM consisted not only of basal septal hypertrophy but a combination with LV lengthening, apical dilatation, and LVOT inward remodelling. Salient differences were observed between obstructive cases at rest and stress. Genotype negative cases showed a tendency towards more obstructive phenotypes both at rest and stress., Conclusions: LV anatomy underpinning oHCM consists of basal septal hypertrophy, apical dilatation, LV lengthening, and LVOT inward remodelling. Differences between oHCM cases at rest and stress, as well as the relationship between LV phenotype and genotype, suggest different mechanisms for LVOTO. Proposed Z-scores render an opportunity of redefining management strategies based on the relationship between LV anatomy and LVOTO., Competing Interests: Conflict of interest: P.L. sits at the scientific advisory board of Ultromics. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Remote monitoring (RM) is the standard of care for follow up of patients with cardiac implantable electronic devices. The aim of this study was to compare smartphone-based RM (SM-RM) using patient applications (myMerlinPulse™ app) with traditional bedside monitor RM (BM-RM)., Methods and Results: The retrospective study included de-identified US patients who received either SM-RM or BM-RM capable of implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators (Abbott, USA). Patients in SM-RM and BM-RM groups were propensity-score matched on age and gender, device type, implant year, and month. Compliance with RM was quantified as the proportion of patients enrolling in the RM system (Merlin.net™) and transmitting data at least once. Connectivity was measured by the median number of days between consecutive transmissions per patient. Of the initial 9714 patients with SM-RM and 26 679 patients with BM-RM, 9397 patients from each group were matched. Remote monitoring compliance was higher in SM-RM; significantly more patients with SM-RM were enrolled in RM compared with BM-RM (94.4 vs. 85.0%, P < 0.001), similar number of patients in the SM-RM group paired their device (95.1 vs. 95.0%, P = 0.77), but more SM-RM patients transmitted at least once (98.1 vs. 94.3%, P < 0.001). Connectivity was significantly higher in the SM-RM, with patients transmitting data every 1.2 (1.1, 1.7) vs. every 1.7 (1.5, 2.0) days with BM-RM ( P < 0.001) and remained better over time. Significantly more SM-RM patients utilized patient-initiated transmissions compared with BM-RM (55.6 vs. 28.1%, P < 0.001)., Conclusion: In this large real-world study, patients with SM-RM demonstrated improved compliance and connectivity compared with BM-RM., Competing Interests: Conflict of interest: H.M.: consultant for Abbott. H.B.: speaker fees, institutional fellowship support or research grants from Abbott, Biotronik, Boston Scientific, Medtronic and Microport. R.C.-A.: speaker fees of small amount from Abbott, Johnson and Johnson. N.V.: research/PI/SC member/consultant for Abbott, Biotronik, Boston Scientific, EP Solutions, Medtronic, Impulse Dynamics, Implicity, Pacemate, Cardiologs. C.L.: speaker fees from Bayer, AstraZeneca. D.K.: consultant for Abbott, Biotronik, Boston Scientific, Medtronic. Speaker fees of small amount from Abbott and Medtronic. G.C.-W.: research funding and speaker fees from Pfizer Medtronic BMS and Abbott. K.K., I.R., Y.N.- employment and stock, Abbott. G.B.: speaker fees of small amount from Bayer, Boehringer, Boston, Daiichi., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To characterize the most common electrocardiographic (ECG) abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), including anterior T-wave inversion (TWI) and to compare the characteristics of TWI in patients with ARVC and in a cohort of young healthy athletes and sedentary individuals., Methods and Results: The study population consisted of 162 patients with a definite diagnosis of ARVC and 129 young controls with anterior TWI. Cardiac disease was excluded in all controls after a comprehensive diagnostic work-up. The ECG was abnormal in 131 patients with ARVC (81%). Abnormalities included anterior TWI (n = 82, 51%), QRS duration ratio V2:V5 >1.2 (n = 51, 31%), prolonged terminal S wave activation duration in V2 >55 ms (n = 42, 26%), inferior TWI (n = 30, 18%), and lateral TWI (n = 26, 16%). The J-point preceding anterior TWI was <0.1 mV in 80/82 (98%) patients with ARVC and in 98 (76%) controls. Among the ARVC patients with anterior TWI, 62 (77%) showed at least one additional abnormal feature, most commonly QRS duration ratio V2:V5 > 1.2 (52%) and inferior or lateral TWI (47%)., Conclusion: The ECG is frequently abnormal in patients with ARVC and anterior TWI is the most common feature. Anterior TWI is usually accompanied by other abnormalities in ARVC, which are uncommon in healthy individuals. J point <0.1 mV preceding anterior TWI is not specific to ARVC and is observed in the majority of healthy individuals, including athletes, indicating a limited role for differentiating physiology or normal variants from ARVC.

Introduction: Community-based participatory research [CBPR] is an emerging approach to collaborative research aimed at creating locally effective and sustainable interventions. The 2040 Partners for Health student program was developed as a unique model of longitudinal CBPR. Analysis of this program and its components illuminates both the challenges and the opportunities inherent in community engagement., Methods: The program rests on a foundation of a community-based, non-profit organization and a supportive academic university centre. Inter-professional health students and community members of underserved populations work together on different health projects by employing an adapted CBPR methodology. Three successful examples of sustainable CBPR projects are briefly described., Results: The three projects are presented as primary outcomes resulting from this model. Benefits and challenges of the model as an approach to community-engaged research are discussed as well as secondary benefits of student participation., Conclusion: The 2040 Partners for Health student program represents a successful model of CBPR, illuminating common challenges and reiterating the profound value of community-engaged research., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To estimate UK prevalence and incidence of clinically significant carbapenemase-producing Enterobacteriaceae (CPE), and to determine epidemiological characteristics, laboratory methods and infection prevention and control (IPC) measures in acute care facilities., Methods: A 6 month survey was undertaken in November 2013-April 2014 in 21 sentinel UK laboratories as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) project. Up to 10 consecutive, non-duplicate, clinically significant and carbapenem-non-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were submitted to a reference laboratory. Participants answered a questionnaire on relevant laboratory methods and IPC measures., Results: Of 102 isolates submitted, 89 (87%) were non-susceptible to ≥1 carbapenem, and 32 (36%) were confirmed as CPE. CPE were resistant to most antibiotics, except colistin (94% susceptible), gentamicin (63%), tigecycline (56%) and amikacin (53%). The prevalence of CPE was 0.02% (95% CI = 0.01%-0.03%). The incidence of CPE was 0.007 per 1000 patient-days (95% CI = 0.005-0.010), with north-west England the most affected region at 0.033 per 1000 patient-days (95% CI = 0.012-0.072). Recommended IPC measures were not universally followed, notably screening high-risk patients on admission (applied by 86%), using a CPE 'flag' on patients' records (70%) and alerting neighbouring hospitals when transferring affected patients (only 30%). Most sites (86%) had a laboratory protocol for CPE screening, most frequently using chromogenic agar (52%) or MacConkey/CLED agars with carbapenem discs (38%)., Conclusions: The UK prevalence and incidence of clinically significant CPE is currently low, but these MDR bacteria affect most UK regions. Improved IPC measures, vigilance and monitoring are required., (© Crown copyright 2016.)

Aims: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible., Methods and Results: To determine the feasibility and diagnostic yield of targeted exome sequencing deoxyribonucleic acid (DNA) was isolated from 59 SADS victims (mean age 25 years, range 1-51 years). Targeted exome sequencing of 135 genes associated with cardiomyopathies and ion channelopathies was performed on the Illumina HiSeq2000 platform. Non-synonymous, loss-of-function, and splice-site variants with a minor allele frequency <0.02% in the NHLBI exome sequencing project and an internal set of control exomes were prioritized for analysis followed by <0.5% frequency threshold secondary analysis. First-degree relatives were offered clinical screening for inherited cardiac conditions. Seven probands (12%) carried very rare (<0.02%) or novel non-sense candidate mutations and 10 probands (17%) had previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands., Conclusion: Molecular autopsy using targeted exome sequencing has a relatively low diagnostic yield of very rare potentially disease causing mutations. Candidate pathogenic variants with a higher frequency in control populations are relatively common and should be interpreted with caution., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Transmural lesion formation is critical to success in atrial fibrillation ablation and is dependent on left atrial wall thickness (LAWT). Pre- and peri-procedural planning may benefit from LAWT measurements., Methods and Results: To calculate the LAWT, the Laplace equation was solved over a finite element mesh of the left atrium derived from the segmented computed tomographic angiography (CTA) dataset. Local LAWT was then calculated from the length of field lines derived from the Laplace solution that spanned the wall from the endocardium or epicardium. The method was validated on an atrium phantom and retrospectively applied to 10 patients who underwent routine coronary CTA for standard clinical indications at our institute. The Laplace wall thickness algorithm was validated on the left atrium phantom. Wall thickness measurements had errors of <0.2 mm for thicknesses of 0.5-5.0 mm that are attributed to image resolution and segmentation artefacts. Left atrial wall thickness measurements were performed on 10 patients. Successful comprehensive LAWT maps were generated in all patients from the coronary CTA images. Mean LAWT measurements ranged from 0.6 to 1.0 mm and showed significant inter and intra patient variability., Conclusions: Left atrial wall thickness can be measured robustly and efficiently across the whole left atrium using a solution of the Laplace equation over a finite element mesh of the left atrium. Further studies are indicated to determine whether the integration of LAWT maps into pre-existing 3D anatomical mapping systems may provide important anatomical information for guiding radiofrequency ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Participation of patients with heart failure in cardiac rehabilitation in the UK is low. This study investigated the availability of cardiac rehabilitation services for patients with heart failure in the UK and the views of service coordinators on ideal service models., Design: Our study was a cross-sectional national postal survey that was mailed to 342 service coordinators in the UK between April and June 2009., Methods: We developed a 38-item questionnaire to survey all cardiac rehabilitation service coordinators on the National Audit of Cardiac Rehabilitation register in the UK in 2009., Results: The survey response rate was 71% (244/342). Forty three per cent (105/244) of coordinators did not accept patients with heart failure to their cardiac rehabilitation services. Most coordinators who did accept patients with heart failure offered their services to patients with a variety of cardiac conditions, though referral criteria and models of care varied widely. Services inconsistently used New York Heart Association classes and left ventricular ejection fraction measures to select patients. Few offered separate dedicated heart failure programmes (14%; 33/244) but where these existed they ran for longer than programmes which included patients with heart failure alongside other cardiac patients (10.9 vs 8.5 weeks; F = 4.04; p = 0.019). Few offered home-based options for patients with heart failure (11%; 27/244). Coordinators accepting patients with heart failure to their cardiac rehabilitation services tended to agree that patients with heart failure should be included in services alongside other cardiac patients (χ(2) = 6.2; p = 0.013)., Conclusions: There is limited access for patients with heart failure to cardiac rehabilitation in the UK. Local policies on referral and selection criteria differ and reflect coordinators' views rather than clinical guidance., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aims: Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead., Methods and Results: Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration., Conclusion: Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: Left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT) is largely empirical and operator-dependent. Our aim was to determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the acute and the chronic response., Methods and Results: CMR-derived anatomical models and dyssynchrony maps were created for 20 patients. The CMR targets (three latest activated segments with <50% scar) were overlaid on to live fluoroscopy. Acute haemodynamic response (AHR) to LV pacing was assessed using an intra-ventricular pressure wire. Chronic CRT response (end-systolic volume reduction ≥15%) was assessed 6 months post-implantation. All patients underwent successful CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients. The mean change in LVdP/dtmax for the CMR target was +14.2 ± 12.5 vs. +18.7 ± 11.9% for the best AHR in any segment and +12.0 ± 13.8% for the segment based on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were echocardiographic responders. Of the echocardiographic responders, 92% were successfully paced in a CMR target segment compared with only 50% of non-responders (P = 0.04)., Conclusion: CMR guidance compared well when validated against the AHR. Lead placement was possible in the CMR target region in most patients with an AHR comparable with the best achieved in any CS branch. The chronic response was significantly better in patients paced in a CMR target segment. These results suggest that CMR guidance may represent a clinically useful tool for CRT.