Paul Clift

Background: The aim of this study was to evaluate the intersectionality between measured causes of health inequality and clinical factors that influence treatment decisions and regional variations in care and survival for people with thoracic aortic disease (TAD) in England. Methods: The target population was all new TAD diagnoses in English hospitals between April 2013 and March 2018 with at least a 1‐year follow‐up. Adjusted regression models analyzed the associations between age, sex, race and ethnicity, socioeconomic deprivation, and geographic region with 1‐year all‐cause death, early elective thoracic aortic intervention, and referral for imaging surveillance or clinical genetics screening. Results: The analysis cohort included 33 793 new TAD diagnoses with complete baseline and follow‐up data. In multivariate analyses, older patients, women, and people from economically deprived areas, were more likely to die within 1 year of diagnosis. Exploratory analyses showed that older people, people of Asian or Black race, and those from deprived areas were less likely to undergo early treatment, and older people, women, and people from deprived areas were more likely to undergo surveillance scans within 6 months of diagnosis. People from areas of deprivation were less likely to be referred for genetic screening. After adjustment for baseline differences and health inequalities, there was significant regional variation in the proportion of people with newly diagnosed TAD who underwent treatment and aortic surveillance. Conclusions: There are multilevel sources of inequality in access to care and survival following a diagnosis with TAD in England. These findings expose a significant evidence‐to‐practice gap and the need for national strategies to implement equitable standardized care pathways.

Cascade screening enables effective secondary prevention and early treatment for Thoracic Aortic Disease (TAD) and increases survival. Despite guideline recommendations, the uptake of screening remains low. This study investigated individual and organisational barriers to screening participation. We performed clinician and public focus groups ( n = 19 participants across 5 sessions), semi-structured interviews (4 clinicians) and a national patient/relative survey ( n = 242 responses: 71 probands, 171 relatives). Behavioural theories guided data interpretation and thematic analysis. Data collection explored motivations, psychological and practical burdens, communication dynamics and attitudes towards screening and Decision Support Tools (DSTs). A national survey of TAD patients and their families provided quantitative context on demographics, genetic testing uptake and involvement in shared decision-making. Thematic analysis using the framework approach was applied to qualitative data. Qualitative analysis of focus groups, interviews and a national patient/relative survey ( n = 242) identified significant barriers to TAD cascade screening, including fragmented services, inconsistent clinician knowledge and patient confusion regarding genetic testing pathways. Survey data showed low genetic testing uptake (47% survivors; 44% and 21% for first- and second-degree relatives). Conversely, key facilitators for a DST included user-friendliness, multi-modal accessibility, clear risk/benefit communication and the inherent value of reassurance with professional endorsement from healthcare providers. These would directly address observed psychological and practical burdens. Patient and family engagement in TAD cascade screening faces complex barriers, including psychological burdens and systemic issues, resulting in a substantial shared decision-making gap. User-centric, multi-modal Decision Support Tools, supported by enhanced clinician education and structured family communication, are vital for effective TAD prevention

Adult congenital heart disease (ACHD) patients often require non-cardiac surgery (NCS) and the need of such interventions is growing as the population ages. The intricacies inherent to their distinct physiology pose ACHD patients at a higher risk of perioperative complications, perioperative mortality, longer length of stay, and higher hospital charges compared with the general population. While 2020 ESC guidelines comprehensively address most aspects of ACHD care, they do not cover this specific area. Furthermore, although risk assessment for non-cardiac surgery is included in the 2022 ESC Guidelines on Cardiovascular Assessment and Management of Patients Undergoing Non-Cardiac Surgery, the unique pathophysiology of ACHD patients necessitates tailored considerations. The aim of this clinical consensus statement is to address the specific situations and needs of ACHD patients undergoing NCS from a multidisciplinary and practical point of view and to describe the organization of care for this complex group of patients. A group of experienced professionals from 4 cardiology and anaesthesiology scientific societies [the ESC Working Group on ACHD, the European Society of Anaesthesiology and Intensive Care (ESAIC), the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC), and the International Society of Adult Congenital Heart Disease (ISACHD)] have evaluated the available scientific data and reached expert consensus in areas of gaps in evidence.

Aims: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). PAH following CHD repair (repaired PAH-CHD) is an emerging population with increased morbidity and mortality. Existing PAH risk scores are unvalidated in young children with this condition. Methods and results: A 20-year cohort from the UK National Paediatric PH Service was studied to describe peri-operative characteristics and outcomes in children with repaired PAH-CHD and to create a tailored risk stratification tool. This tool was externally validated using the national Spanish PH (REHIPED) registry. The study included 178 patients (median age 3.2 years, 58.4% female), with 73.0% referred post-CHD repair. Complex CHD was present in 61.2%, and 48.9% had both pre- and post-tricuspid shunts. Down syndrome was noted in 33.1%. At initial post-operative assessment, 53.1% exhibited symptoms like breathlessness, 30.9% had moderate–severe right ventricular dilatation, and 23.7% showed right ventricular systolic impairment. During a median six-year follow-up of 156 patients, 19.2% died and 3.2% required lung transplantation, with survival rates at one, five, and ten years being 94.7%, 85.9%, and 80.1%, respectively. The developed risk score, based on clinical variables including absence of pre-operative PH, breathlessness, right ventricular dysfunction, and pulmonary vascular resistance index, showed good performance and calibration in predicting outcomes. Conclusion: In this national cohort of children with repaired PAH-CHD, mortality is significant. This novel, simple risk score has been developed and validated specifically for children with repaired PAH-CHD, useful at the time of post-operative assessment to predict outcome and direct management.

Background Cascade screening enables effective secondary prevention and early treatment for Thoracic Aortic Disease (TAD) and increases survival. Despite guideline recommendations, the uptake of screening remains low. This study investigated individual and organisational barriers to screening participation. Methods We performed clinician and public focus groups (n = 19 participants across 5 sessions), semi-structured interviews (4 clinicians), and a national patient/relative survey (n = 242 responses: 71 probands, 171 relatives). Behavioural theories guided data interpretation and thematic analysis. Data collection explored motivations, psychological and practical burdens, communication dynamics, and attitudes towards screening and Decision Support Tools (DSTs). A national survey of TAD patients and their families provided quantitative context on demographics, genetic testing uptake, and involvement in shared decision-making. Thematic analysis using the framework approach was applied to qualitative data. Results Qualitative analysis of focus groups, interviews, and a national patient/relative survey (n = 242) identified significant barriers to TAD cascade screening, including fragmented services, inconsistent clinician knowledge, and patient confusion regarding genetic testing pathways. Survey data showed low genetic testing uptake (47% survivors; 44% and 21% for first- and second-degree relatives). Conversely, key facilitators for a DST included user-friendliness, multi-modal accessibility, clear risk/benefit communication, and the inherent value of reassurance with professional endorsement from healthcare providers, directly addressing observed psychological and practical burdens. Conclusions Patient and family engagement in TAD cascade screening faces complex barriers, including psychological burdens and systemic issues, resulting in a substantial shared decision-making gap. User-centric, multi-modal Decision Support Tools, supported by enhanced clinician education and structured family communication, are vital for effective TAD prevention

Background: Fabry disease (FD) causes multiorgan sphingolipid accumulation, with cardiac involvement responsible for the largest burden of morbidity and mortality. Exercise intolerance in FD is prevalent, yet the mechanisms of this are poorly understood. The aim of this study was to assess exercise intolerance in FD and identify whether this correlates with the phase of cardiomyopathy.Methods: This was a retrospective observational study of adults with FD undergoing cardiopulmonary exercise testing (CPEX) between September 2011 and September 2023 at a national referral centre in the UK. The primary outcome measure was peak oxygen uptake (V̇O_2peak), with forced expiratory volume in 1 s (FEV₁) used to quantify respiratory impairment. Age-normalised/sex-normalised values were additionally calculated, based on published normal ranges for subgroups of age and sex. The cardiomyopathy phase was classified on a 4-point scale by two FD experts using contemporaneous imaging and biochemistry results.Results: CPEX was completed by 42 patients, with a median age of 54 years and of whom 62% were male. Patients were approximately equally distributed across the four cardiomyopathy phases. At phase I, the mean (±SD) V̇O_2peakwas 28.7±7.7 mL/kg/min, which represented a significant underperformance of 23%, relative to age-normalised and sex-normalised values (expected mean: 37.3±3.2 mL/kg/min, p=0.006). V̇O_2peakdeclined significantly across the cardiomyopathy phases (p=0.010), reaching a mean of 21.2±6.1 mL/kg/min at phase IV. Normalised FEV₁was not found to show a corresponding significant change with cardiomyopathy phase (p=0.683). Impaired left atrial global longitudinal strain as well as biochemical markers of inflammation were associated with impaired V̇O_2peak.Conclusions: This study identifies significantly impaired aerobic capacity in FD, even in those without phenotypic cardiomyopathy. No corresponding changes in respiratory impairment were observed, suggesting that exercise intolerance may be due to early cardiac sphingolipid accumulation and subsequent atrial and ventricular dysfunction, which increases as cardiomyopathy progresses. As such, peak V̇O_2peakholds promise as a therapeutic marker of response to FD-specific therapy.

Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy. Aortas from patients and animal models exhibit raised cellular reactive oxygen species, oxidative DNA damage and VSMC apoptosis. Antioxidant exposure or chelation of iron prevents oxidative damage in patient’s cells and aortopathy in the zebrafish model. Our observations suggest a key role for oxidative stress and cell death, including via ferroptosis, in mediating aortic degeneration.

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a progressive, life-limiting disease.In this paper, we review the classification and pathophysiology of PAH-CHD...