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Background: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort., Methods: In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59 868 and 62 266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420 071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR)., Results: Mean PR interval and QRS duration were 144.2 ms (± 20.4) and 92.3 ms (± 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95% CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered., Conclusions: Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age., Competing Interests: Competing interests: JD serves on scientific advisory boards for AstraZeneca, Novartis and UK Biobank and has received multiple grants from academic, charitable and industry sources outside of the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Atrial fibrillation (AF) prediction improves by combining clinical scores with a polygenic risk score (PRS) for AF (AF-PRS), but there are limited studies of PRS for ventricular arrhythmia (VA) prediction., Objective: We assessed the value of including multiple PRS for cardiovascular risk factors (CV-PRS) for incident AF and VA prediction., Methods: We used 158,733 individuals of European ancestry from UK Biobank to build three models for AF: CHARGE-AF (AF1), AF1 + AF-PRS (AF2), AF2 + CV-PRS (AF3). Models for VA included sex and age (VA1), VA1 + coronary artery disease (CAD) PRS (CAD-PRS, VA2), and VA2 + CV-PRS (VA3), conducting separate analyses in subjects with and without ischemic heart disease (IHD). Performance was evaluated in individuals of European (N=158,733), African (N=7,200), South Asian (N=9,241) and East Asian (N=2,076) ancestry from UK Biobank., Results: AF2 had a higher C-index than AF1 (0.762 versus 0.746, P<0.001), marginally improving to 0.765 for AF3 (P<0.001, including PRS for heart failure, electrocardiogram and cardiac magnetic resonance measures). In South Asians, AF2 C-index was higher than AF1 (P<0.001). For VA, the C-index for VA2 was greater than VA1 (0.692 versus 0.681, P<0.001) in Europeans, which was also observed in South Asians (P<0.001). VA3 improved prediction of VA in individuals with IHD., Conclusion: CV-PRS improved AF prediction compared to CHARGE-AF and AF-PRS. A CAD-PRS improved VA prediction, while CV-PRS contributed in IHD. AF- and CAD-PRS were transferable to individuals of South Asian ancestry. Our results inform of the use of CV-PRS for personalised screening., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This scoping review was undertaken to identify risk predictions models and preoperative predictors of surgical site infection (SSI) in adult cardiac surgery. A particular focus was on the identification of novel predictors that could underpin the future development of a risk prediction model to identify individuals at high-risk of SSI, and therefore guide a national SSI prevention strategy., Methods: A scoping review to systematically identify and map out existing research evidence on preoperative predictors of SSI was conducted in two stages. Stage 1 reviewed prediction modelling studies of SSI in cardiac surgery. Stage 2 identified primary studies and systematic reviews of novel cardiac SSI predictors., Results: The search identified 7887 unique records; 7154 studies were excluded at abstract screening and 733 studies selected for full-text assessment. Twenty-nine were included for Stage 1 and reported the development (n = 14), validation (n = 13), or both the development and validation (n = 2) of 52 SSI risk prediction models including 67 different preoperative predictors. The remaining 703 studies were re-assessed for Stage 2; 49 studies met the inclusion criteria, and 56 novel preoperative predictors not yet assessed in models were identified., Conclusions: This review identified 123 preoperative predictors of SSI risk following cardiac surgery, 56 of which have not been previously included in the development of cardiac SSI prediction models. These candidate predictors will be a valuable resource in the future development of risk prediction scores and may be relevant to SSI risk prediction in other surgical specialities., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dilated cardiomyopathy (DCM) is extensively discussed in numerous expert consensus documents and international guidelines, with differing recommendations. To support clinicians in daily practice and decision-making, we conducted a systematic review of key guidelines and recommendations concerning the diagnosis and clinical management of DCM. Our research encompassed MEDLINE and EMBASE databases for relevant articles published, as well as the websites of relevant scientific societies. We identified two guidelines and one scientific statement that met stringent criteria, thereby qualifying them for detailed systematic analysis. Our review revealed consensus on several key aspects: the definition of DCM, the use of B-type natriuretic peptides and high-sensitivity troponin in laboratory testing, the essential role of multimodality cardiovascular imaging for initial diagnosis, genetic counselling, and the management of advanced disease. Nonetheless, notable areas of variation included the formation of multidisciplinary management teams, the role of cascade genetic testing, pathways for arrhythmic risk stratification, and the criteria for prophylactic defibrillator implantation. Significant evidence gaps persist, particularly regarding the clinical trajectory of genetic, non-genetic and gene-elusive forms of DCM, the use of cardiovascular magnetic resonance in phenotype-negative family members with genotype-positive probands, and the development of potential aetiology-oriented therapies. Addressing these gaps could enhance clinical outcomes and inform future research directions and guideline development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Explainable artificial intelligence (XAI) emerged to improve the transparency of machine learning models and increase understanding of how models make actions and decisions. It helps to present complex models in a more digestible form from a human perspective. However, XAI is still in the development stage and must be used carefully in sensitive domains including paediatrics, where misuse might have adverse consequences., Objective: This commentary paper discusses concerns and challenges related to implementation and interpretation of XAI methods, with the aim of rising awareness of the main concerns regarding their adoption in paediatrics., Methods: A comprehensive literature review was undertaken to explore the challenges of adopting XAI in paediatrics., Results: Although XAI has several favorable outcomes, its implementation in paediatrics is prone to challenges including generalizability, trustworthiness, causality and intervention, and XAI evaluation., Conclusion: Paediatrics is a very sensitive domain where consequences of misinterpreting AI outcomes might be very significant. XAI should be adopted carefully with focus on evaluating the outcomes primarily by including paediatricians in the loop, enriching the pipeline by injecting domain knowledge promoting a cross-fertilization perspective aiming at filling the gaps still preventing its adoption., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Cardiology training in the UK is facing significant challenges due to a range of factors. Recent curriculum changes have further compounded this issue and significantly risk the ability to produce adequately trained consultants capable of managing patients with increasingly complex cardiovascular disease. The introduction of mandatory dual accreditation in general internal medicine (GIM) alongside cardiology, by design, results in significantly reduced training opportunities, including procedural and subspecialty exposure. Despite prolongation in training duration to mitigate these effects, most trainees now report needing post-certificate of completion of training fellowships to gain the standard competencies required for consultant roles, undermining the curriculum's aim of fostering independent practice. Furthermore, the current training model is misaligned with patient needs, lacking provisions for training in key and expanding services, such as complex structural interventions and inherited cardiac conditions. The increasing complexity of expectations placed on trainees also has the potential to significantly hinder academic training, discouraging research and innovation, thereby risking the future of UK clinical academia. Urgent curriculum reform is not only desirable but also essential and should include limiting GIM training time, improving subspecialty accreditation pathways and revising academic training provisions. If current bodies overseeing cardiology training fail to implement these essential changes, additional options, including an independent regulatory framework for cardiology training, should be considered. Without immediate action, UK cardiology training risks facing a generational crisis of inadequately skilled consultants, which could compromise future patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Breast hamartomas are rarely associated with epithelial atypia or malignancy. Since the introduction of digital mammography in the UK from 2008, hamartoma detection has increased. The aim of this study was to identify if there are characteristic clinical, radiological or histological features that distinguish hamartomas with intralesional atypia/malignancy (complex hamartomas, CH) or ipsilateral/contralateral atypia/malignancy (non-CH) from those without atypia/malignancy at diagnosis (other benign hamartomas, BH)., Methods: We performed a retrospective single-institution review of 450 hamartomas reported between 2010 and 2023. Anonymised H&E sections and imaging of CH and non-CH were reviewed to identify distinguishing features., Results: 13,441 benign breast lesions were biopsied/resected between 2010 and 2023 including 450 hamartomas (3.3%), 19 of which (4.2%) were associated with atypia or malignancy. 14 were analysed further (7 CH; 7 non-CH). The mean age of CH plus non-CH patients was significantly higher than patients with BH (47.5 vs. 40.6 years; p = 0.03). The mean size of CH was greater than non-CH (32.1 mm vs.17.6 mm; p = 0.06). There was a statistically significantly higher incidence of atypical/malignant lobular lesions (ALH/LCIS/ILC) in CH vs. non-CH (42.9% vs 0%; p = 0.05). MRI was performed in 2 CH and 3 non-CH; in all 5 the associated malignancy was detected. There was no significant difference between the CH and non-CH group in ultrasound/mammographic features, other hamartoma histological features or other associated benign breast changes., Conclusions: Ultrasound/mammogram are not sufficiently sensitive to identify hamartomas with associated atypia/malignancy. Certain hamartoma features may preferentially be associated with atypia/malignancy and which merit further radiological and/or detailed histological investigation., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

People living with resistant hypertension (RH) are at high risk of adverse cardiovascular events. The British and Irish Hypertension Society has identified suspected RH as a condition for which specialist guidance may improve rates of blood pressure control and help clinicians identify those individuals who may benefit from specialist review. In this position statement we provide a practical approach for the investigation and management of adults with RH. We highlight gaps in the current evidence and identify important future research questions. Our aim is to support the delivery of high-quality and consistent care to people living with RH across the UK and Ireland., Competing Interests: Competing interests: Professor Adrian J.B. Brady has received honoraria from Daiichi-Sankyo, Amgen, Sanofi-Aventis, Bayer, MSD, and Novartis. Professor Phil Chowienczyk has an interest in Centron Diagnostics, a company that has produced technology for blood pressure measurement. Professor Jacob George has received grants and travel funding from Astra Zeneca, Novartis and Daiichi Sankyo, is on Advisory Boards for AstraZeneca, Menarini and Novartis, consulting fees from Roche and PwC and is a Principal Investigator for studies funded by AstraZeneca, Alnylam, Novartis, Esperion. Dr Pankaj Gupta has received research grants, lecture honoraria and funding for conference attendance from Sanofi-Aventis and Amgen, and consulting fees from Ionis Pharmaceuticals. Professor Anthony Heagerty has received lecture honoraria from Servier. Dr Spoorthy Kulkarni is a PhD student at the University of Cambridge funded by AstraZeneca and has attended scientific advisory boards for Viatris. Professor Terry McCormack has received lecture honoraria and/or consultation fees from AstraZeneca, Daichi-Sankyo, and Medtronic. He is a co-investigator in the Alnylam study Kardia 3. Professor Neil R Poulter has received lecture honoraria and/or consultation fees from several pharmaceutical companies that manufacture blood pressure lowering agents including AstraZeneca, Eva Pharma, Lri Therapharma, Napi, Pfizer, Servier and Sanofi-Aventis. Professor Ian B Wilkinson has received research grants from AstraZeneca, GSK and scientific advisory board consultation fees for Viatris, Astra Zeneca and Roche. Dr Luca Faconti, Dr Carmen Maniero, Dr Vikas Kapil, Dr Philip Lewis, Ms Michaela Nuttall, Mr Sam Olden, Dr Sarah Partridge, Dr Alfredo Petrosino, Dr Abilash Sathyanarayanan, Professor Peter Sever, Dr Wayne Sunman and Dr Helen Warren have no competing interests to declare for this manuscript., (© 2024. The Author(s).)

Background: Coronary sinus reducer (CSR) implantation is emerging as a novel effective percutaneous therapy for patients with refractory angina. Limited data exists examining the factors influencing successful CSR implantation. As CSR implantation becomes more widely adopted, a greater understanding of the procedural challenges which operators encounter is required., Aim: To evaluate the patient and procedural characteristics influencing successful CSR implantation., Methods: This was a retrospective cohort study of consecutive patients with refractory angina undergoing clinically indicated CSR implantation (February 2016 to August 2024) at a high-volume implanting centre in the UK. Patient and procedural characteristics affecting procedural difficulty were systematically analysed. Procedural difficulty was determined by 1) increasing total procedural time or 2) features of challenging equipment handling such as bellying, swan-necking or complete equipment fallout from the coronary sinus (CS)., Results: 102 out of 105 (97 %) patients underwent a successful CSR implant at the first attempt. Patients had a high rate of previous revascularisation (PCI: 85 %; CABG 64 %) and diabetes (58 %). Significant improvements in Canadian Cardiovascular Society (CCS) class were observed with 36 % of patients improving by ≥2 CCS classes and 71 % improving by ≥1 CCS class. A C- or non-C-shape of the CS was not associated with differences in procedural time (P = 0.52). However, the presence of both a valve and ridge in the CS was associated with significantly longer procedural times (P = 0.03). A ridge, alone or together with a valve, predicted features of procedural difficulty, such as bellying (ridge - OR: 2.69, P = 0.02; valve and ridge - OR: 4.58, P = 0.0006) and swan-necking (ridge - OR: 5.43, P = 0.001; valve and ridge - OR: 4.74, P = 0.002). Bellying, swan-necking, and complete fallout of equipment from the CS were associated with longer procedural times, but also with each other, suggesting their utility as indicators of procedural complexity., Conclusion: In our experience, CSR implantation is safe and associated with high rates of procedural success. However, patient and procedural factors can influence the difficulty of CSR implantation. The presence of a ridge may make implantation more challenging. Bellying, swan-necking and complete equipment fallout may indicate increased procedural complexity. Greater awareness of these features will encourage operators to remain vigilant and adapt their implantation strategy when encountering challenging cases., Competing Interests: Declaration of competing interest Ranil de Silva reports a relationship with Shockwave Medical Inc. that includes: non-financial support and speaking and lecture fees. Ranil de SIlva reports a relationship with Abbott Vascular Inc. that includes: non-financial support and speaking and lecture fees. Jonathan Hill reports a relationship with Abbott that includes: non-financial support and speaking and lecture fees. Jonathan Hill reports a relationship with AbioMed Inc. that includes: non-financial support and speaking and lecture fees. Jonathan Hill reports a relationship with Boston Scientific Corporation that includes: non-financial support and speaking and lecture fees. Jonathan Hill reports a relationship with Shockwave Medical Inc. that includes: non-financial support and speaking and lecture fees. Jonathan Hill reports a relationship with Shockwave Medical Inc. that includes: equity or stocks. Christos Papageorgiou reports a relationship with AbioMed Inc. that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Here we present long-term outcomes of first line afatinib in comorbid patients with suspected or confirmed EGFR mutant NSCLC otherwise considered unsuitable for chemotherapy, and the clinical utility of serial ctDNA monitoring., Methods: TIMELY (NCT01415011) was a multicentre, single arm, phase II trial conducted in the UK. Patients aged ≥18 were treated with daily oral afatinib (40 mg) until disease progression or unacceptable toxicity. Blood samples for ctDNA analysis were obtained at baseline and 12-weekly until treatment discontinuation. The primary endpoint was PFS., Results: Thirty-nine patients were enrolled between March 2013 and August 2015. Median follow-up was 98 months (range 69-101). Median PFS was 7.9 months (95% CI 4.6-10.5). Seven patients (18%) continued afatinib beyond 18 months, 3 beyond 36 months and 2 were still on treatment at last follow-up 101 months post-treatment initiation. Analysis of baseline ctDNA samples identified 8 EGFR mutant cases that were not identified by tissue genotyping and ctDNA clearance was associated with improved PFS and OS., Conclusion: Afatinib is a viable treatment option for tissue or ctDNA-detected EGFR mutant NSCLC comorbid patients, with a proportion achieving long-term clinical benefit. Plasma ctDNA testing improved EGFR mutant identification and its clearance predicted improved PFS and OS., Competing Interests: Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Popat’s has consulting /advisory Role with Amgen, AstraZeneca (AZ), Bayer, Blueprint, Bristol Myers Squibb (BMS), Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline (GSK), Guardant Health, Incyte, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme (MSD), Novartis, Roche, Takeda, Pfizer, Seattle Genetics, Turning Point Therapeutics & EQRx. He has received payment/Honoraria from AstraZeneca, Bayer, Guardant Health, Janssen, Merck Serono, Roche & Takeda. He has provided expert testimony to Roche, Merck Serono. He has received meeting attendance support from Janssen & Roche. He has a leadership / fiduciary Role with the British Thoracic Oncology Group (BTOG), ALK Positive UK, Lung Cancer Europe, Ruth Strauss Foundation, Mesothelioma Applied Research Foundation & ETOP-IBCSG Partners Foundation Board. Dr Januszewski has received grant/holds contracts with Gilead & Roche. He has received teaching payments from AZ, Johnson and Johnson, Roche, Pfizer, MSD & Bayer. He has received meeting attendance support from Johnson & Johnson Pharmaceuticals & Roche Pharmaceuticals. He has an advisory role with BMS, AZ, Pfizer & MSD. He has a leadership/fiduciary role with BTOG. Dr Ahmad has received speaker payment from AZ. She has received payment for an advisory project from Roche and meeting attendance support from Takeda. Dr Shah has an advisory role with BI. He has received meeting attendance support from BI. He has a leadership / fiduciary role with BTOG & EGFR + UK. Dr Geldart has received honoraria from Merck and meeting attendance support from BMS. Prof Spicer has consulting compensation to author’s employer from AZ, BMS, GSK & RS Oncology; Advisory Board fees. He has an advisory role with CHM Cancer Vaccines Expert Working Group & CHM Expert Advisory Group on Oncology & Haematology. He has a leadership /fiduciary role with BTOG & Experimental Cancer Medicine Centres. He has stock/stock Options with Avacta & Epsiolgen. He has received reimbursements for treatment of trial patients from Achilles, BergenBio, BMS, Gilead, IO Biotech, Iovance, MSD, Roche, RS Oncology, Starpharma & Trizell. Dr Roitt has limited prior shares with Inivata. Dr Mulatero has stocks with Inivata. All remaining authors had no conflicts of interest to declare. Ethical approval and consent to participate: The TIMELY trial was approved by the Scotland A Research Ethics Committee. Written informed consent was obtained from all patients. The study was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Background: A significant proportion of cardiomyopathy patients remain genetically unsolved. Our aim was to use the large genomes cohort of the 100,000 genomes project (100KGP) to explore the proportion of potentially causal mitochondrial (mtDNA) variants in cardiomyopathy patients, particularly in genotype-elusive participants. The homoplasmic MT-TI 4300A>G is unusual in that it typically presents with a cardiac-only phenotype, but MT-TI is currently not part of the genes analysed for non-syndromic cardiomyopathies., Results: We analysed 1363 cardiomyopathy genomes from the 100KGP project (of which only 172 had been previously solved) to detect disease causing mtDNA variants. MitoHPC was used to call variants. For controls, 1329 random subjects not recruited for a cardiomyopathy diagnosis and not related to any participant in the cardiomyopathy cohort were selected. We have additionally compared the frequency of detected variants with published UK Biobank data. Pathogenicity annotations were assigned based on MitoMap. Four patients, all with a diagnosis of hypertrophic cardiomyopathy (HCM) and without a previously identified genetic cause from the 100KGP clinical-standard analysis, were found to harbour the pathogenic MT-TI m.4300A>G variant (0.6% of HCM cases without a diagnosis)., Conclusion: These data support the inclusion of MT-TI in the initial genetic testing panel for (non-syndromic) HCM., Competing Interests: Declarations. Ethics approval and consent to participate: The 100KGP was approved by the relevant Research Ethics Committee (REC) [East of England—Cambridge South (REC ref. 14/EE/1112)] and all participants provided informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objective: Advances in molecular diagnostics have ushered in a new era for patients with prostate, renal, and urothelial cancers, with novel radiographic and molecular modalities for the assessment of disease burden and minimal residual disease (MRD). Conventional imaging has a limited threshold for disease detection and is often unable to discern clinically occult disease with varying risks of false-negative or false-positive findings depending on the disease state and type of imaging., Methods: We provide an overview of emerging radiographic and molecular tools in development within the genitourinary (GU) disease space. A literature review of contemporary basic, translational, and clinical research studies was performed, covering the timeframe of 1980-2024 through the MEDLINE (via PubMed) and Scopus databases. We highlight select examples of emerging technologies and biomarker-informed clinical trials, which aim to quantify disease at lower thresholds and have the potential for integrating MRD in clinical practice for GU patients., Key Findings and Limitations: The development of novel radiotracers, such as prostate-specific membrane antigen or carbonic anhydrase IX, is being evaluated in both clinical practice and trial setting, aiming to change the management of these tumors. Molecular tools including circulating tumor cells and byproducts such as plasma and urine cell-free circulating tumor DNA provide the opportunity for MRD detection. MRD capture on single-cell or cellular byproducts can serve as a conduit for genomic and transcriptomic analyses, providing insight into the molecular underpinnings and clonal evolution of disease., Conclusions and Clinical Implications: While the full potential for MRD applications has yet to be realized, we are witnessing the emergence of novel techniques aimed at MRD detection and the rapid development of elegantly designed studies implementing iterative detection of MRD as means to provide biological rationale and tailor therapeutic options in GU tumors., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In the modern era, cardiologists managing patients and families with cardiomyopathies need to be familiar with every stage of the diagnostic pathway from clinical phenotyping to the prescription and interpretation of genetic tests. This clinical consensus statement from the ESC Council for Cardiovascular Genomics aims to promote the integration of genetic testing into routine cardiac care of patients with cardiomyopathies, as recommended in the 2023 ESC guidelines for cardiomyopathies. The document describes the types of genetic tests currently available and provides advice on their prescription and for counselling after the return of genetic findings, including the approach in patients and families with variants of unknown significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Cardiovascular magnetic resonance (CMR) is increasingly used in the diagnosis of myocarditis, with myocardial injury and systolic dysfunction playing key roles in the prognosis of this clinical setting. The clinical determinants of myocardial injury and systolic impairment in acute myocarditis are poorly defined. The aim of the current study is to assess the association of laboratory markers, late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF) in patients with acute myocarditis., Methods: We completed a retrospective cohort study from a tertiary referral centre in London with CMR and acute myocarditis. Cases with cardiomyopathy were excluded. Missing data was imputed for selected clinical variables. We evaluated the association between peak troponin and LGE extent and LVEF. We adjusted the models for age, sex and time to CMR with a sensitivity analysis adjusting for body mass index and cardiovascular risk factors including hypertension, dyslipidaemia, diabetes mellitus and smoking., Results: 127 patients had abnormal T2-weighted imaging/mapping results with 118 (93%) presenting with chest pain and/or shortness of breath. Left ventricular LGE was identified in 118 (93%) patients and LVEF was 58±11%. The median time from the peak troponin to CMR was 1 day (IQR 0-6 days). The highest tertile of peak troponin was associated with more LGE (incident rate ratio 1.33, 95% CI: 1.07 to 1.64) and a lower LVEF (coefficient -5.3%, 95% CI: -9.5% to -1.1%). Diabetes was also associated with more LGE (incident rate ratio 1.90, 95% CI: 1.37 to 2.61) and lower LVEF (coefficient -8.9%, 95% CI: -14.7% to -1.8%)., Conclusions: Peak troponin is associated with more LGE and a lower LVEF even after accounting for demographics and comorbidities. Myocardial injury and systolic dysfunction play key roles in prognosis and future work incorporating clinical features into a risk prediction model may enable better risk stratification in acute myocarditis., Competing Interests: Competing interests: SEP reports a consultancy for Circle Cardiovascular Imaging, Inc., Calgary, Alberta, Canada., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Patients with reduced left ventricular ejection fraction (LVEF) and rate-controlled atrial fibrillation (AF) may improve after restoring sinus rhythm. This may be due to the elimination of the short R-R intervals during AF even when mean heart rate is acceptable., Objectives: This work aims to evaluate a novel parameter representing the burden of short R-R intervals during AF and its association with reduced LVEF and LVEF recovery after catheter ablation (CA)., Methods: Patients with persistent AF were prospectively enrolled pre-CA and grouped as having reduced (LVEF ≤50%) or preserved LVEF. Sequential R-R intervals on resting Holter monitoring were measured. We sought to define a threshold R-R interval at which the difference in the percentage of short R-R intervals is greatest when comparing patients with reduced and preserved ejection fraction. We termed this threshold the restitution threshold (RT) in the belief that this may be possible to apply as a threshold to identify patients with AF-mediated cardiomyopathy. This percentage burden of intervals shorter than the RT was defined as the restitution threshold index (RTI). The association with reduced LVEF in AF and predicting improvement in LVEF after CA was then evaluated., Results: One hundred four patients were enrolled; 53 (51%) had a reduced LVEF. There was no difference in mean heart rate; however, at an RT of 660 ms, the RTI was higher in the reduced LVEF arm (56.1% ± 23.1% vs 39.5% ± 26.0%; P < 0.001). It was an independent predictor of left ventricular systolic dysfunction. The RTI in the reduced LVEF arm had an area under the receiver operating characteristic of 0.74 (95% CI: 0.47-0.95) and positive predictive value of 0.97 for LVEF improvement after CA, which was observed in 39 of 47 (83.0%) participants in sinus rhythm., Conclusions: The RTI in persistent AF was associated with a reduced LVEF, whereas mean heart rate was not. The RTI could be used to predict LVEF improvement after CA., Competing Interests: Funding Support and Author Disclosures This study was funded by a Clinical Research Training Fellowship grant from Barts Charity and a Research Grant from Abbott Inc. Drs Honarbakkhsh, Hunter, and Schilling were inventors of the STAR mapping system and are shareholders in Rhythm AI Ltd. Dr Hunter has received research grants and educational grants from Medtronic and Biosense Webster; and has received speaker fees and travel grants from Abbott, Biosense Webster, and Medtronic. Dr Schilling has received research grants and educational grants from Abbott, Biosense Webster, and Medtronic; and has received speaker fees and travel grants from Abbott, Biosense Webster, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) has been proposed as an alternative to intravascular imaging for assessing plaque pathology., Aims: We aimed to assess the efficacy of CCTA against near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) in evaluating atheroma burden and composition and for guiding coronary interventions., Methods: Seventy patients with a chronic coronary syndrome were recruited and underwent CCTA and NIRS-IVUS. The imaging data were matched, and the estimations of lumen, vessel wall and plaque dimensions and composition of the two modalities were compared. The primary endpoint of the study was the efficacy of CCTA in detecting lipid-rich plaques identified by NIRS-IVUS. Secondary endpoints included the performance of CCTA in evaluating coronary artery pathology in the studied segments and its value in stent sizing, using NIRS-IVUS as the reference standard., Results: In total, 186 vessels were analysed. The attenuated plaque volume on CCTA had weak accuracy in detecting lipid-rich plaques (58%; p=0.029). Compared to NIRS-IVUS, CCTA underestimated the lumen volume (309.2 mm 3 vs 420.4 mm 3 ; p=0.001) and plaque dimensions (total atheroma volume 116.1 mm 3 vs 292.8 mm 3 ; p<0.001 and percentage atheroma volume 27.67% vs 41.06%; p<0.001) and overestimated the lipid component (lipid core burden index 48.6 vs 33.8; p=0.007). In the 86 lesions considered for revascularisation, CCTA underestimated the reference vessel area (8.16 mm 2 vs 12.30 mm 2 ; p<0.001) and overestimated the lesion length (23.5 mm vs 19.0 mm; p=0.029) compared to NIRS-IVUS., Conclusions: CCTA has limited efficacy in assessing plaque composition and quantifying lumen and plaque dimensions and tissue types, which may potentially impact revascularisation planning.

Background: Surgical site infection (SSI) is a common type of hospital-acquired infection and affects up to a third of patients following surgical procedures. It is associated with significant mortality and morbidity. In the United Kingdom alone, it is estimated to add another £30 million to the cost of adult cardiac surgery. Although generic guidance for SSI prevention exists, this is not specific to adult cardiac surgery. Furthermore, many of the risk factors for SSI are prevalent within the cardiac surgery population. Despite this, there is currently no standard of care for SSI prevention in adults undergoing cardiac surgery throughout the preoperative, intraoperative and postoperative periods of care, with variations in practice existing throughout from risk stratification, decontamination strategies and surveillance., Objectives: Primary objective: to assess the clinical effectiveness of pre-, intra-, and postoperative interventions in the prevention of cardiac SSI., Secondary Objectives: (i) to evaluate the effects of SSI prevention interventions on morbidity, mortality, and resource use; (ii) to evaluate the effects of SSI prevention care bundles on morbidity, mortality, and resource use., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid, from inception) and Embase (Ovid, from inception) on 31 May 2021., Clinicaltrials: gov and the WHO International Clinical Trials Registry Platform (ICTRP) were also searched for ongoing or unpublished trials on 21 May 2021. No language restrictions were imposed., Selection Criteria: We included RCTs evaluating interventions to reduce SSI in adults (≥ 18 years of age) who have undergone any cardiac surgery., Data Collection and Analysis: We followed the methods as per our published Cochrane protocol. Our primary outcome was surgical site infection. Our secondary outcomes were all-cause mortality, reoperation for SSI, hospital length of stay, hospital readmissions for SSI, healthcare costs and cost-effectiveness, quality of life (QoL), and adverse effects. We used the GRADE approach to assess the certainty of evidence., Main Results: A total of 118 studies involving 51,854 participants were included. Twenty-two interventions to reduce SSI in adults undergoing cardiac surgery were identified. The risk of bias was judged to be high in the majority of studies. There was heterogeneity in the study populations and interventions; consequently, meta-analysis was not appropriate for many of the comparisons and these are presented as narrative summaries. We focused our reporting of findings on four comparisons deemed to be of great clinical relevance by all review authors. Decolonisation versus no decolonisation Pooled data from three studies (n = 1564) using preoperative topical oral/nasal decontamination in all patients demonstrated an uncertain direction of treatment effect in relation to total SSI (RR 0.98, 95% CI 0.70 to 1.36; I 2 = 0%; very low-certainty evidence). A single study reported that decolonisation likely results in little to no difference in superficial SSI (RR 1.35, 95% CI 0.84 to 2.15; moderate-certainty evidence) and a reduction in deep SSI (RR 0.36, 95% CI 0.17 to 0.77; high-certainty evidence). The evidence on all-cause mortality from three studies (n = 1564) is very uncertain (RR 0.66, 95% CI 0.24 to 1.84; I 2 = 49%; very low-certainty evidence). A single study (n = 954) demonstrated that decolonisation may result in little to no difference in hospital readmission for SSI (RR 0.80, 95% CI 0.44 to 1.45; low-certainty evidence). A single study (n = 954) reported one case of temporary discolouration of teeth in the decolonisation arm (low-certainty-evidence. Reoperation for SSI was not reported. Tight glucose control versus standard glucose control Pooled data from seven studies (n = 880) showed that tight glucose control may reduce total SSI, but the evidence is very uncertain (RR 0.41, 95% CI 0.19 to 0.85; I 2 = 29%; numbers need to treat to benefit (NNTB) = 13; very-low certainty evidence). Pooled data from seven studies (n = 3334) showed tight glucose control may reduce all-cause mortality, but the evidence is very uncertain (RR 0.61, 95% CI 0.41 to 0.91; I 2 = 0%; very low-certainty evidence). Based on four studies (n = 2793), there may be little to no difference in episodes of hypoglycaemia between tight control vs. standard control, but the evidence is very uncertain (RR 2.12, 95% CI 0.51 to 8.76; I 2 = 72%; very low-certainty evidence). No studies reported superficial/deep SSI, reoperation for SSI, or hospital readmission for SSI. Negative pressure wound therapy (NPWT) versus standard dressings NPWT was assessed in two studies (n = 144) and it may reduce total SSI, but the evidence is very uncertain (RR 0.17, 95% CI 0.03 to 0.97; I 2 = 0%; NNTB = 10; very low-certainty evidence). A single study (n = 80) reported reoperation for SSI. The relative effect could not be estimated. The certainty of evidence was judged to be very low. No studies reported superficial/deep SSI, all-cause mortality, hospital readmission for SSI, or adverse effects. Topical antimicrobials versus no topical antimicrobials Five studies (n = 5382) evaluated topical gentamicin sponge, which may reduce total SSI (RR 0.62, 95% CI 0.46 to 0.84; I 2 = 48%; NNTB = 32), superficial SSI (RR 0.60, 95% CI 0.37 to 0.98; I 2 = 69%), and deep SSI (RR 0.67, 95% CI 0.47 to 0.96; I 2 = 5%; low-certainty evidence. Four studies (n = 4662) demonstrated that topical gentamicin sponge may result in little to no difference in all-cause mortality, but the evidence is very uncertain (RR 0.96, 95% CI 0.65 to 1.42; I 2 = 0%; very low-certainty evidence). Reoperation for SSI, hospital readmission for SSI, and adverse effects were not reported in any included studies., Authors' Conclusions: This review provides the broadest and most recent review of the current evidence base for interventions to reduce SSI in adults undergoing cardiac surgery. Twenty-one interventions were identified across the perioperative period. Evidence is of low to very low certainty primarily due to significant heterogeneity in how interventions were implemented and the definitions of SSI used. Knowledge gaps have been identified across a number of practices that should represent key areas for future research. Efforts to standardise SSI outcome reporting are warranted., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes., Patients and Methods: TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively. The association was evaluated in each treatment arm using logistic regression [objective response rate (ORR)] and Cox proportional hazards regression models (PFS and OS); one-sided (pembrolizumab monotherapy; pembrolizumab plus chemotherapy) and two-sided (chemotherapy) nominal P values were calculated. Significance was prespecified at α = 0.05 without multiplicity adjustment. Efficacy was evaluated by prespecified cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1)., Results: Of the 993 treated patients, 820 (82.6%) and 993 (100%) had evaluable TMB and CPS data, respectively. Continuous TMB was positively associated with ORR, PFS, and OS for pembrolizumab monotherapy (one-sided P < 0.001, P < 0.001, and P = 0.007, respectively); PFS and OS for pembrolizumab plus chemotherapy (one-sided P = 0.007 and P = 0.010, respectively); and OS for chemotherapy alone (two-sided P = 0.040). Continuous PD-L1 CPS showed evidence of anticipated association with ORR and PFS for pembrolizumab monotherapy. The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone., Conclusions: These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma., (©2024 The Authors; Published by the American Association for Cancer Research.)

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics., Competing Interests: Competing interests: S.L.Z. has acted as a consultant for Health Lumen. A.H. and R.T.L. have received funding from Pfizer Inc. R.T.L. has performed paid consultancy for Health Lumen and Fitfile Ltd. J.S.W. has acted as a consultant for MyoKardia, Pfizer, Foresite Labs and Health Lumen and received institutional support from Bristol Myers Squibb and Pfizer Inc. P.C. has received personal fees for consultancies, outside the present work, for Amicus, Pfizer Inc., Owkin and Bristol Myers Squibb. M.-P.D. declares holding equity in Dalcor Pharmaceuticals, unrelated to this work. The authors who are affiliated with deCODE genetics/Amgen Inc. and Regeneron Pharmaceuticals declare competing financial interests as employees. The other authors declare no competing interests., (© 2024. The Author(s).)

VHL disease is an inherited and autosomal dominant disorder affecting 1 in 36,0000 individuals worldwide. It is caused by von Hippel-Lindau (VHL) gene mutations and can affect both genders and all ethnic backgrounds (Nordstrom-O'Brien et al., 2009; Maher, 2004). Here, we generated and characterised two iPSC lines derived from patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and VHL Type 1 enrolled in the TRACERx Renal (TRAcking Renal Cell Carcinoma Evolution Through Therapy (Rx)). PBMCs were reprogrammed to pluripotency using a genome non-integrating Sendai virus (SeV) vectors protocol. Both human iPSC lines displayed normal morphology, expressed markers associated with stemness and differentiated into the three germ layers. The iPSC lines could be used as a disease-specific cellular model to understand furtherthe inherited disorder of Type 1 von Hippel-Lindau (VHL) disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis with current treatment options including chemotherapy and androgen receptor signaling inhibitor (ARSI) medications. Poly-ADP ribose polymerase (PARP) inhibitors alone and in combination with ARSI has recently been incorporated in management for mCRPC deficient in BRCA1/2 genes. However, downregulating androgen-receptor signaling using ARSIs can upregulate the PI3K/AKT/mTOR pathway, promoting tumor cell survival. This creates a rationale for co-targeting both these pathways. This systematic review aimed to investigate AKT inhibitors and ARSI combination therapy., Methods: EMBASE, MEDLINE, and Scopus were searched from database inception to July 2023. Primary outcomes included objective response rate (ORR), prostate-specific antigen (PSA) response rate, adverse events (AEs), overall survival (OS), and radiographic progression-free survival (rPFS). Quality was assessed using the risk of bias tool (ROB2) and certainty of evidence with GRADE., Results: Six clinical trials with 3 Phase I, 1 Phase II, 1 Phase III were included with 771 patients and a median age ranging from 67 years to 70 years. The pooled ORR was 30% (n = 5 studies, 95% CI, 3%-84%) and PSA response rate was 43% (n = 5 studies, 95% CI, 15%-77%). The median duration of rPFS ranged from 8.2 to 19.2 months in the intervention compared with 6.4 to 16.6 months in the placebo group. A 16% reduction in radiographic progression or death was reported in patients receiving dual therapy compared with those receiving placebo. This reduction was greater by PTEN-loss status, ranging from 23% to 61%. The median OS ranged from 15.6 to 18.9 months. No significant difference was reported in survival relative to placebo. 98.8% (767/776) of patients experienced AEs of any grade, with GRADE ≥3 AEs occurring in 65.9% (512/776) of patients. The most common AE and GRADE ≥3 AEs were diarrhoea (pooled prevalence = 70%, 95% CI, 57%-81%), and hyperglycaemia (pooled prevalence = 12%, 95% CI, 6%-20%), respectively., Conclusion: Combined therapy reduced the risk of rPFS, with the response higher in PTEN-loss subgroup, with a modest but not significant increase in OS. Our AE estimates showed consistency with other studies. AEs of any grade were common with the majority experiencing at least 1 AE. (PROSPERO Registration Number: CRD420202352583)., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy and a leading cause of sudden death. Genetic testing and familial cascade screening play a pivotal role in the clinical management of HCM patients. However, conventional genetic tests primarily focus on the detection of exonic and canonical splice site variation. Oversighting intronic non-canonical splicing variants potentially contributes to a proportion of HCM patients remaining genetically undiagnosed. Here, using a non-integrative reprogramming strategy, we generated induced pluripotent stem cell (iPSC) lines from four individuals carrying one of two variants within intronic regions of MYBPC3: c.1224-52G > A and c.1898-23A > G. Upon differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), mis-spliced mRNAs were identified in cells harbouring these variants. Both abnormal mRNAs contained a premature termination codon (PTC), fitting the criteria for activation of nonsense mediated decay (NMD). However, the c.1898-23A > G transcripts escaped this mRNA quality control mechanism, while the c.1224-52G > A transcripts were degraded. The newly generated iPSC lines represent valuable tools for studying the functional consequences of intronic variation and for translational research aimed at reversing splicing abnormalities to prevent disease progression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.C.-F. is a co-founder and advisor for “GenoMed-Diagnósticos de Medicina Molecular, SA”; she reports research support by AbbVie and Gilead Sciences, outside of the scope of this study; she also received speaker fees from Novartis, Janssen, AstraZeneca and Alnylam. L.R.L speaker fee Alnylam, Sanofi-Genzyme and BMS and consulting fees BMS and Novo Nordisk. Research grant from BMS. The remaining authors have nothing to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: Randomised data on patient-reported outcomes (PROs) for stereotactic body radiotherapy (SBRT) and prostatectomy in localised prostate cancer are lacking. PACE-A compared patient-reported health-related quality of life after SBRT with that after prostatectomy., Methods: PACE is a phase 3 open-label, randomised controlled trial. PACE-A randomised men with low- to intermediate-risk localised prostate cancer to SBRT or prostatectomy (1:1). Androgen deprivation therapy (ADT) was not permitted. The coprimary outcomes were the Expanded Prostate Index Composite (EPIC-26) number of absorbent urinary pads required daily and bowel domain score at 2 yr. The secondary endpoints were clinician-reported toxicity, sexual functioning, and other PROs., Key Findings and Limitations: In total, 123 men were randomised (60 undergoing prostatectomy and 63 SBRT) from August 2012 to February 2022. The median follow-up time was 60.7 mo. The median age was 65.5 yr and the median prostate-specific antigen (PSA) value 7.9 ng/ml; 92% had National Comprehensive Cancer Network (NCCN) intermediate-risk disease. Fifty participants received prostatectomy and 60 received SBRT. At 2 yr, 16/32 (50%) prostatectomy and three of 46 (6.5%) SBRT participants used one or more urinary pads daily (p < 0.001; 15 and two, respectively, used one pad daily); the estimated difference was 43% (95% confidence interval [CI]: 25%, 62%). At 2 yr, bowel scores were better for prostatectomy (median [interquartile range] 100 [100-100]) than for SBRT (87.5 [79.2-100]; p < 0.001), with an estimated mean difference of 8.9 between these (95% CI: 4.2, 13.7); sexual scores were worse for prostatectomy (18 [13.8-40.3]) than for SBRT (62.5 [32.0-87.5]). The limitations were slow recruitment and incomplete 2-yr PRO response rates., Conclusions and Clinical Implications: SBRT was associated with less patient-reported urinary incontinence and sexual dysfunction, and slightly more bowel bother than prostatectomy. These randomised data should inform treatment decision-making for patients with localised, intermediate-risk prostate cancer., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Not all patients experience debilitating symptoms during Atrial Fibrillation (AF), some are asymptomatic. The reasons for this inter- and intrasubject variability is unknown., Purpose: The study objective was NOAH characterize episode-level and clinical characteristics associated with symptomatic versus asymptomatic episodes of AF in patients with an implantable cardiac monitor (ICM)., Methods: Patients with an AF episode detected on an ICM between 2007 and 2021 with overlapping clinical data from aggregated Electronic Health Records in the Optum® deidentified data set were included. Symptomatic episodes were labeled in real-time by the patient. Heart rate (HR) at onset, mean HR, AF Evidence Score (a measure of beat-to-beat irregularity), episode duration and Activity Index were evaluated for association with symptom status using multivariable regression modeling., Results: 11 267 patients had AF episodes with clinical data available. The 1776 (15.8%) patients who reported symptomatic AF episodes were younger (67 ± 12 years vs. 71 ± 11 years old, p < .001) and had fewer cardiovascular co-morbidities than patients with asymptomatic AF exclusively. Symptomatic episodes were longer (5.5 [2.4, 14.4] h vs. 3.7 [1.7, 11] h, p < .001), had higher mean HR (103 ± 22 bpm vs. 88 ± 22 bpm, p < .001) and higher AF evidence scores (98 ± 27 vs. 82 ± 24, p < .001). These features were independently associated with symptomatic episodes on multivariable regression analysis and per-subject analysis in patients who had both symptomatic and asymptomatic episodes., Discussion: Episode-level characteristics differed between symptomatic AF episodes versus asymptomatic episodes in patients with ICMs. Symptomatic patients also had less comorbidities. These parameters may be useful in understanding variable symptomatic manifestation and remote stratification of AF episodes., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non-invasively. At the population level, the prognostic role of CMR-modelled PCWP remains unknown. Furthermore, the relationship between CMR-modelled PCWP and established risk factors for cardiovascular disease has not been well characterized., Objective: The main aim of this study was to investigate the prognostic value of CMR-modelled PCWP at the population level., Methods: Employing data from the imaging substudy of the UK Biobank, a very large prospective population-based cohort study, CMR-modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR-modelled PCWP (≥15 mmHg). Cox regression was used to examine the impact of typical risk factors and CMR-modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE)., Results: Data from 39 163 participants were included in the study. Median age of all participants was 64 years (inter-quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR-modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44-1.70, P < 0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52-1.62, per standard deviation (SD) increment, P < 0.001], male sex (OR 1.37, 95% CI 1.26-1.47, P < 0.001), age (OR 1.33, 95% CI 1.27-1.41, per decade increment, P < 0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02-1.19, P = 0.012). After adjusting for potential confounders, CMR-modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07-4.07, P < 0.001] and MACE (HR 1.48, 95% CI 1.16-1.89, P = 0.002)., Conclusions: Raised CMR-modelled PCWP is an independent risk factor for incident HF and MACE. CMR-modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours., Competing Interests: Competing interests R.T.C. has received a Novartis speaker honorarium and is in an editorial position in Clinical Endocrinology. C.J. has received funding to his institution from Lantheus, Progenics, Exelixis, Merck Sharpe and Dohme and is a clinical adviser for Lantheus and Merck Sharpe and Dohme. S.D.M. is the Director of the NIHR Clinical Research Facility at Great Ormond Street Hospital, London. D.T. has received speaker and attendance honoraria from AAA/NOVARTIS. M.F. is an unpaid member of the ExCo of the European Society of Endocrinology. J.W.M.L. is an unpaid member of the advisory board of the Phaeochromocytoma and Paraganglioma Alliance., (© 2024. Crown.)

The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild-type aberrations. Twenty-four-week overall response rate was 50% (60% CI 39.3%-60.7%), and median duration of response was 11.6 months (IQR: 6.3-17). The median progression-free survival was 13.6 months (95% CI 3-19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune-mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD-1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Spinal cord ischemia (SCI) is a potentially devastating complication of thoracic endovascular aortic repair (TEVAR) and fenestrated-branched endovascular aortic repair (F-BEVAR). The aim of this systematic review was to evaluate the efficacy of neuromonitoring modalities to mitigate the risk of SCI during TEVAR and F-BEVAR procedures., Methods: Following the PRISMA guidelines, we conducted a detailed literature search of databases including PubMed, MEDLINE via Ovid, Embase, Scopus, and Cochrane CENTRAL, from 1998 to the present. Inclusion criteria were original research articles examining neuromonitoring during TEVAR and F-BEVAR. The primary outcome was the incidence of SCI, while the secondary outcome included early mortality. The quality of studies was assessed using the Newcastle-Ottawa Scale., Results: From 1,450 identified articles, 11 met inclusion criteria, encompassing data from 1,069 patients. Neuromonitoring modalities included motor-evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), and near-infrared spectroscopy. The combination of MEPs and SSEPs was most commonly used, with 93% sensitivity and 96% specificity for detecting SCI risks. SCI incidence ranged from 3.8 to 17.3%, with permanent deficits occurring in 2.7-5.8% of cases. In-hospital mortality ranged from 0.4 to 8%. Risk factors for SCI were identified, including operation duration and extent of aortic coverage., Conclusions: Neuromonitoring with MEPs and SSEPs appears to be effective in detecting perioperative SCI risk during TEVAR and F-BEVAR. However, discrepancies between neuromonitoring changes and actual SCI outcomes suggest the need for cautious interpretation. While the incidence of SCI remains variable, identified risk factors may guide clinical decisions, particularly in high-risk procedures. Future research should focus on prospective studies and randomized controlled trials to validate these findings and improve SCI prevention strategies in TEVAR and F-BEVAR., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Areas of abnormal or heterogeneous conduction velocity (CV) are important ablation targets for ventricular tachycardias, yet precise assessment of CV in clinical contact mapping remains challenging. Numerous different CV estimation methods have been proposed., Objective: This study aimed to compare the automated local activation time (LAT)-independent omnipolar-based CV estimation method termed wave speed (WS) with 4 established LAT-based methods to formally establish the quantitative differences between them., Methods: High-density contact maps in patients with structurally normal hearts during sinus rhythm (SR) and ventricular ectopy (VE) were retrospectively analyzed. CV was assessed and compared by 5 methods: omnipolar WS, gradient method, planar wavefront fitting, circular wavefront fitting, and radial basis function. CV variations based on electrogram (EGM) type (unipolar, bipolar, and omnipolar), catheter movement, and surrogate markers for catheter contact were analyzed., Results: The study included 23 patients (47.8% male; 45.7 ± 17.3 years) with 22 SR maps (11 left ventricle, 11 right ventricle) and 16 VE maps (9 left ventricle, 7 right ventricle). The WS algorithm yielded statistically significant higher CV estimates in SR (mean, 1.41 ± 0.18 m/s) and VE (mean, 1.23 ± 0.18 m/s) maps compared with all LAT-based estimation methods, with absolute differences ranging from 0.1 m/s to 0.81 m/s. Median pointwise differences in SR and VE between WS and LAT-based methods were high, ranging from 0.55 ± 0.15 m/s (WS vs planar wavefront fitting) to 0.67 ± 0.16 m/s (WS vs radial basis function). For LAT-based methods, use of unipolar EGMs yielded significantly higher CV estimates than bipolar or omnipolar EGMs in SR., Conclusion: The CV estimation method has an important, statistically significant impact on ventricular CV measurements. Future work will focus on how these differences affect identification of pathologic conduction slowing in scar-related substrate., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Blunt thoracic aortic injury (BTAI) represents one of the most devastating scenarios of vascular trauma. Different management strategies are available with varying clinical outcomes. However, thoracic endovascular aortic repair (TEVAR) has become the first-line option for most BTAI patients, mainly owing to its minimally invasive nature, yielding improved immediate results. This meta-analysis aims to investigate mortality, long-term survival, and reintervention following TEVAR in BTAI., Material and Methods: A systematic review conducted a comprehensive literature search on multiple electronic databases using strict search terms. Twenty-seven studies met the set inclusion/exclusion criteria. A proportional meta-analysis of extracted data was conducted using the Comprehensive Meta-Analysis Software, v.4., Results: 1498 BTAI patients who underwent TEVAR were included. Using the SVS grading system, 2.6% of the population had Grade 1 injuries, 13.6% Grade 2, 62.2% Grade 3, 19.6% Grade 4, and 1.9% unspecific. All-cause mortality did not exceed 20% in all studies except one outlier with a 37% mortality rate. Using the random effects model, the pooled estimate of overall mortality was 12% (95% confidence interval [CI], 5.35-8.55%; I 2  = 70.6%). This was 91% (95% CI, 88.6-93.2; I 2  = 30.2%) at 6 months, 90.1% (95% CI, 86.7-92.3; I 2  = 53.6%) at 1 year, 89.2% (95% CI, 85.2-91.8; I2 = 62.3%) at 2 years, and 88.1% (95% CI, 83.3-90.9; I 2  = 69.6%) at 5 years. Moreover, the pooled estimate of reintervention was 6.4% (95% CI, 0.1-0.49%; I 2  = 81.7%)., Conclusions: Despite the high morbidity and mortality associated with BTAI, TEVAR has proven to be a safe and effective management strategy with favorable long-term survival and minimal need for reintervention. Nevertheless, diagnosis of BTAI requires a high index of suspicion with appropriate grading and prompt transfer to trauma centers with appropriate TEVAR facilities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs)., Methods and Results: We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12 months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR = 1.51, 95% CI = 1.35-1.68; beta-blockers: OR = 1.22, 95% CI = 1.08-1.37; MRAs: OR = 1.31, 95% CI = 1.08-1.59) and poor persistence (RASIs: OR = 2.04, 95% CI = 1.75-2.37; beta-blockers: OR = 1.35, 95% CI = 1.12-1.63; MRAs: OR = 1.49, 95% CI = 1.16-1.93), and higher risks for dose down-titration for RASIs (OR = 1.69, 95% CI = 1.40-2.04) and beta-blockers (OR = 1.31, 95% CI = 1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs., Conclusions: Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Increasing numbers of people are seeking assisted conception. In people with known cardiac disease or risk factors for cardiac disease, assisted conception may carry increased risks during treatment and any subsequent pregnancy. These risks should be assessed, considered and minimized prior to treatment.

Introduction: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications., Materials and Methods: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures., Results: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions., Conclusions: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements., Competing Interests: Conflict of Interest Ganesan Baranidharan has received consulting fees from Abbott, Boston Scientific, Medtronic, and Saluda Medical; has received honoraria from Abbott, Boston Scientific, Mainstay Medical, Saluda Medical, Stryker, and Nevro Corp; and sits on the international data safety board for Saluda Medical. Stana Bojanić sits on the board of the International Neuromodulation Society. Sam Eldabe has received departmental grants from Boston Scientific and Saluda Medical; and consulting fees from Medtronic, Saluda Medical, Mainstay Medical, and Esteve Pharmaceutical. James J. FitzGerald has received institutional research grants from Merck and UCB; consulting fees from Abbott and Lilly; educational honoraria from Abbott; and advisory board fees from Medtronic and Abbott. Sarah Love-Jones has received travel honoraria from Boston Scientific, Nevro Corp, Abbott, Medtronic, and Saluda Medical; research grants from Boston Scientific, Mainstay Medical, Nevro Corp, Saluda Medical, Nalu Medical, and Abbott; and sits on the medical advisory board for Boston Scientific, Nevro Corp, Saluda Medical, Medtronic, and Pfizer. Vivek Mehta has received consulting fees from Mainstay Medical, Lundbeck, Pfizer, Boston Scientific, and Medtronic; holds an advisory position with Medtronic, Pfizer, and Man & Science; and sits on the board of the Neuromodulation Society of UK and Ireland, and the Education Committee of the North American Neuromodulation Society. Simon Thomson has received grants, honoraria, and consulting fees from Boston Scientific, Mainstay Medical, and Saluda Medical and holds an advisory position with Galvani Bioelectronics. The remaining authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We previously developed and internally validated the Barts Surgical Infection Risk (B-SIR). We sought to explore the external validity of the B-SIR tool and compare with the Australian Clinical Risk Index (ACRI) and Brompton and Harefield Infection Score (BHIS)., Study Design and Setting: This multicentre retrospective analysis of prospectively collected local data included adult (≥18years) patients undergoing cardiac surgery between January 2018 and December 2019. Pre-pandemic data was used as a reflection of standard practice. Area under the curve (AUC) was used to validate and compare the predictive power of the scores and calibration was assessed using Hosmer-Lemeshow test and calibration plots., Results: From three centres, 6,022 patients were included in the complete case analysis. The mean age was 66 years, 75% were men and 3.19% developed SSI. The B-SIR has an AUC of 0.686 (95% CI: 0.649 to 0.723) similar to the developmental study (AUC=0.682; 95% CI: 0.652 to 0.713). This is significantly higher than BHIS AUC=0.610 (95% CI: 0.045 to 0.109; p<0.001) and ACRI AUC=0.614 (95% CI: 0.041 to 0.103; p<0.001). After re-calibration using a correction factor, the B-SIR model gave accurate risk predictions (Hosmer-Lemeshow test p=0.423). Multiple imputation result (AUC=0.676; 95%CI: 0.639 to 0.712) is similar to development data and is higher than ACRI and BHIS., Conclusion: External B-SIR validation indicates B-SIR predicts SSI after cardiac surgery better than ACRI and BHIS risk tools. This suggests B-SIR could be useful to use routinely in practice., Competing Interests: Declaration of Competing Interest none., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflict of interest: none declared.

Introduction: Atrial fibrillation (AF)-induced cardiomyopathy (AIC) is retrospectively defined after normalisation of left ventricular ejection fraction (LVEF) in sinus rhythm. It is unclear why some patients develop AIC., Hypothesis: Patients with AIC have a subtle cardiomyopathic process that precedes their AF-mediated LVEF reduction. Detailed assessment of cardiac function after successful catheter ablation will reveal this., Objective: To evaluate the utility of measures to identify cardiomyopathic features that persist after LVEF normalisation in AIC., Methods: Patients with rate-controlled persistent AF and LVEF<50% undergoing catheter ablation (CA) were prospectively evaluated using echocardiography, cardio-pulmonary exercise testing and serum N-terminal pro b-type natriuretic peptide (NT-proBNP) at baseline and 6 months after CA. Participants with AIC, (LVEF recovery (≥50%) and no other cause for cardiac dysfunction) were evaluated using left ventricular (LV) longitudinal strain and left atrial (LA) reservoir strain (LARS). Changes in peak oxygen consumption and the minute ventilation/carbon dioxide production slope were measured as markers of functional capacity and ventilatory inefficiency. A control group of patients with persistent AF with preserved LVEF were also enrolled., Results: 34/41 (82.9%) participants recovered LVEF in sinus rhythm; defined as AIC. NT-proBNP levels were elevated in 18 (52.9%), and 16 reported ongoing heart failure (HF) symptoms. 10 (29.4%) had no improvement in functional capacity, and seven (20.6%) showed persistent ventilatory inefficiency. 20 (58.8%) had impaired global LV longitudinal strain with a relative apical sparing pattern. Nine (26.5%) had impaired LARS. There was an overlap of these abnormalities. 32 (94.1%) demonstrated at least one, 17 (50.0%) having no cardiovascular risk factors. Patients with preserved LVEF during persistent AF had similar demographics but a lower burden of short R-R intervals (<660 ms) on Holter monitoring., Discussion: Abnormal structural, metabolic and HF biomarkers are seen in patients with AIC in sinus rhythm. These features may represent a precedent subtle cardiomyopathic process predisposing them to left ventricular systolic dysfunction in AF., Trial Registration Number: NCT04987723., Competing Interests: Competing interests: RJH has received research grants and educational grants from Medtronic and Biosense Webster, and speaker fees and travel grants from Abbott and Biosense Webster and Medtronic. RS has received research grants and educational grants from Abbott and Biosense Webster and Medtronic, and speaker fees and travel grants from Abbott and Biosense Webster and Medtronic. RJH, SH and RS were inventors of the STAR mapping system and are shareholders in Rhythm AI. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The emergence of novel programming guidelines that reduce premature and inappropriate therapies along with the availability of new implantable cardioverter-defibrillator (ICD) technologies lacking traditional endocardial antitachycardia pacing (ATP) capabilities requires the reevaluation of ATP as a first strategy in terminating fast ventricular tachycardias (VTs) in primary prevention ICD recipients., Objective: To assess the role of ATP in terminating fast VTs in primary prevention ICD recipients with contemporary programming., Design, Setting, and Participants: This global, prospective, double-blind, randomized clinical trial had an equivalence design with a relative margin of 35%. Superiority tests were performed at interim analyses and the final analysis if equivalence was not proven. Patients were enrolled between September 2016 and April 2021 at 134 sites in 8 countries, with the last date of follow-up on July 6, 2023. Patients were required to have an indication for a primary prevention ICD, including left ventricular ejection fraction less than or equal to 35%., Interventions: Patients were randomized in a 1:1 ratio to receive ATP plus shock vs shock only., Main Outcomes and Measures: The primary end point was time to first all-cause shock. Secondary end points included time to first appropriate shock, time to first inappropriate shock, all-cause mortality, and the composite of time to first all-cause shock plus all-cause mortality., Results: A total of 2595 patients were randomized (mean age, 63.9 years; 22.4% were females). At a mean follow-up of 38 months, first all-cause shock occurred in 129 participants in the ATP plus shock group and 178 participants in the shock only group. The hazard ratio (HR) for the primary end point was 0.72 (95.9% CI, 0.57-0.92), with P = .005 for superiority of the ATP plus shock group over the shock only group. During follow-up in an intention-to-treat analysis, the total shock burden per 100 patient-years was not statistically different, at 12.3 and 14.9, respectively (P = .70)., Conclusions and Relevance: The use of a single burst of ATP prior to shock in primary prevention ICD recipients with modern ICD detection programming prolonged the time to first all-cause ICD shock., Trial Registration: ClinicalTrials.gov Identifier: NCT02923726.

Aim: To investigate current management of advanced epithelial ovarian cancer (OC) in the UK. Materials & methods: A cross-sectional survey with 55 healthcare professionals involved in the care of OC patients was conducted via telephone/videoconference in March/May 2023. Results: Respondents reported that homologous recombination deficiency (HRD) status and brca mutations were routinely tested before planning maintenance treatment. All respondents agreed that cytoreductive surgery should be considered at first recurrence, and 65% recommended using the Descriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) III criteria to guide secondary cytoreduction. Platinum responders typically receive poly (ADP-ribose) polymerase inhibitor maintenance therapy, regardless of HRD status. Conclusion: Respondents reinforce that most primary OC patients in the UK have known HRD and BRCA mutation status, and the role of secondary cytoreduction is increasingly recognized.

Background: GDM and preeclampsia are common complications of pregnancy, for which overweight/obesity is a common risk factor. Both conditions are associated with a two-to-four-fold increase in future incident heart failure, which may be linked to early maladaptive myocardial changes., Objectives: To determine maternal myocardial structural, functional, and energetic responses to pregnancies complicated by gestational diabetes mellitus (GDM) or preeclampsia compared to healthy pregnancies (HP) at third-trimester of pregnancy and twelve-months postpartum., Study Design: Thirty-eight women with HP, 30 GDM, 20 preeclampsia, 10 non-pregnant controls with overweight (Overweight-NC) and 10 with normal-weight were recruited. Cardiovascular magnetic resonance spectroscopy and imaging were used to define myocardial energetics (phosphocreatine: ATP ratio [PCr/ATP]), left ventricular (LV) volumes, mass, and ejection fraction and global longitudinal shortening (GLS). Pregnancy groups underwent repeat scans twelve-months postpartum, nulliparous-controls were assessed once., Results: During third-trimester, compared to HP, women with either GDM or preeclampsia displayed higher BMI, higher LV-mass (HP:90[85,94]g, GDM:103[96,112], Preeclampsia:118[111,125]g; P=0.001), and lower PCr/ATP (HP:2.2[2.1,2.4], GDM:1.9[1.7,2], Preeclampsia:1.9[1.8,2.1];P=0.0004) and GLS (HP:20[18,21]%, GDM:18[17,19]%, Preeclampsia:16[14,17]%;P=0.01). Post-pregnancy, no group saw significant changes in LV-mass, PCr/ATP or GLS. There were no significant differences in LV-mass, PCr/ATP or GLS between the GDM and preeclampsia groups during or post-pregnancy. Moreover, the Overweight-NC showed no significant differences in LV-mass ( 53[43,63])g, PCr/ATP (2.0[1.8,2.2]) or GLS (-19[17,21]%) compared to GDM or preeclampsia groups during or post-pregnancy., Conclusions: Women with GDM or preeclampsia exhibit similar myocardial phenotypes during pregnancy with persistent subclinical alterations in LV mass, energetics and GLS twelve-months postpartum. These myocardial alterations are similar to those detected in Overweight-NC, potentially suggesting the myocardial changes may predominantly be driven by overweight/obesity., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)