BACKGROUND:The Left Atrioventricular Coupling Index (LACI), calculated as the ratio of left atrial (LA) to left ventricular (LV) end-diastolic volume (EDV) has emerged as a novel imaging biomarker of LA-LV coupling. However, reference thresholds are undefined and its predictive value beyond established clinical and imaging markers remains uncertain, limiting broader clinical implementation. METHODS:Two large datasets were leveraged to 1) investigate demographic variations of LACI in health, 2) establish population-specific reference thresholds, 3) characterise the relationship between LACI and cardiac structure/function, and 4) investigate its incremental predictive value for cardiovascular outcomes. Cardiovascular magnetic resonance (CMR) scans were performed and analysed using standardised protocols. In the Healthy Hearts Consortium (HHC), a large image bank of verified healthy individuals, demographic variations of LACI were examined, and population-specific reference thresholds were calculated using the 95% prediction interval method. Associations between LACI and markers of LA/LV structure and function were assessed using linear regression models. In UK Biobank, associations of LACI with incident outcomes [atrial fibrillation (AF), heart failure (HF), myocardial infarction, cardiovascular death, all-cause death] were examined over a median 5.5 years prospective follow-up, using Cox regression models adjusted for demographic, clinical, and established CMR variables. RESULTS:In the HHC (n=7,111, 54% female, median 61.5 years), a higher LACI was observed in older age, ethnicities other than White, and women (who also had a greater age-related increase in LACI). After adjustment for demographic factors, higher LACI was associated with poorer LA function and higher LV filling pressures. In UK Biobank (n=25,849, 52% female, median 63.0 years), higher LACI was independently predictive of incident AF [HR per 1 standard deviation increase 1.31 (1.19, 1.44)] and HF [HR 1.15 (1.07, 1.24)], in Cox models adjusted for demographic, clinical, and established CMR variables. Applying the newly derived reference thresholds in a population-specific manner to the UKB cohort revealed a significantly higher probability of AF and HF amongst those with a raised LACI. CONCLUSION:LACI is a robust predictor of AF and HF with incremental value over established clinical and imaging markers. The provided population-specific reference thresholds permit its broader clinical application.

BACKGROUND:Cardiovascular magnetic resonance (CMR) and electrocardiographic (ECG) abnormalities after coronavirus disease 2019 (COVID-19) are widely reported. However, the absence of pre-infection assessments limits causal inference from these studies. This study aims to compare interval change in CMR and ECG measures in participants with incident COVID-19 and matched uninfected controls in UK Biobank. METHODS:UK Biobank participants with documented COVID-19 who had CMR and ECG performed before the pandemic were invited for repeat assessment, along with uninfected participants matched on age, sex, ethnicity, location, and date of baseline imaging. Automated pipelines were used to extract ECG phenotypes and CMR measures of cardiac structure and function, aortic distensibility, aortic flow, and myocardial native T1. Logistic regression was used to examine associations of baseline metrics with incident COVID-19. Standardized residual approach was used to compare the degree of interval change in CMR and ECG metrics between cases and controls. RESULTS:We analyzed 2092 participants (1079 cases and 1013 controls) with average age of 60 ± 7 years. 47.1% were male. There was 3.2 ± 1.5 years between pre- and post-infection assessments. 3.6% of cases were hospitalized. Lower baseline left ventricular ejection fraction and worse longitudinal, circumferential, and radial strain were associated with higher risk of incident COVID-19. There were no significant differences in interval change of any CMR or ECG metric between cases and controls. CONCLUSION:While pre-existing cardiovascular abnormalities are linked to higher risk of COVID-19, exposure to infection does not alter interval change of highly sensitive CMR and ECG indicators of cardiovascular health.

BACKGROUND:Cardiovascular disease (CVD) burden and risk factor management among cancer survivors, especially in socioeconomically deprived, multiethnic populations, remain understudied. This study examines CVD burden and risk factor control in survivors of 20 cancer types within a diverse urban population. METHODS:This matched cohort study used electronic health records from 127 urban primary care practices. Cancer survivors were matched to non-cancer comparators at a 1:4 ratio. Cancer and CVD diagnoses were defined using standard clinical code sets. Sociodemographic variables, lifestyle behaviours, blood pressure, cholesterol levels and statin prescriptions were analysed. Multivariable regression evaluated associations between cancer history, CVD prevalence and risk factor control. RESULTS:The cohort included 18 839 cancer survivors (43% men, average age 64±15 years), with high ethnic diversity (48% White, 24% Black, 22% Asian) and high deprivation levels. Cancer survivors had elevated odds of all CVDs considered, independent of shared risk factors. Heart failure was more common in haematological (OR 2.12; 95% CI 1.44 to 3.09) and breast cancer survivors (OR 1.38; 95% CI 1.16 to 1.64). Patients with bladder (OR 1.50; 95% CI 1.20 to 1.87) and lung cancer (OR 1.44; 95% CI 1.09 to 1.87) had higher odds of ischaemic heart disease. Venous thromboembolism risk was highest in ovarian cancer (OR 5.72; 95% CI 3.54 to 9.32). Blood pressure control was slightly better in cancer survivors (OR 0.92; 95% CI 0.87 to 0.97), yet one in three patients did not meet guideline-directed targets. Statin use and cholesterol management were similar between survivors and controls, but disparities were observed within certain ethnic groups. CONCLUSION:Cancer survivors have an elevated risk of CVD, with variations by cancer type and ethnicity. Despite comparable or slightly better control of major risk factors, a significant proportion of cancer survivors do not achieve guideline-recommended targets, highlighting the need for optimised management strategies, particularly in high-risk subgroups.

BACKGROUND: Hypertension is a major contributor to cardiovascular morbidity and mortality. Its heterogeneity complicates risk stratification. Unsupervised machine learning can uncover risk profiles and refine preventative strategies. This study applied a data-driven approach to identify clinical phenotypes of hypertension, examine their associations with cardiovascular imaging characteristics and adverse outcomes, and assess the mediating role of cardiac imaging features in these associations. METHODS: Fourteen thousand eight hundred forty UK Biobank participants with diagnosed hypertension and cardiovascular magnetic resonance imaging were analyzed. K-means clustering was applied to 77 clinical variables. Associations with incident heart failure, atrial fibrillation, atherosclerotic events, all-cause mortality, and major adverse cardiovascular events were examined and adjusted for cardiovascular risk factors. Mediation analyses assessed the role of cardiovascular imaging features in the association between clusters and outcomes. RESULTS: Three clusters emerged. Cluster 1, predominantly female with the most favorable metabolic profile, had the lowest risk. Cluster 2, predominantly male with the highest atherosclerosis burden, carried the greatest risk for all adverse events, independent of cardiovascular risk factors. They showed severe cardiac remodeling, impaired cardiac mechanisms, and global left atrial dysfunction. Cluster 3 had a profile resembling metabolic syndrome, with moderate risk for atrial fibrillation and all-cause death (hazard ratio, 1.65 and 1.58; P <0.05). Although in cluster 2 the risk was largely mediated by left ventricular hypertrophy, in cluster 3 its role was attenuated and more evenly balanced with left atrial dysfunction. CONCLUSIONS: Clustering analysis identified distinct hypertension phenotypes with specific risk profiles, suggesting potential for improved stratification and more tailored treatment approaches.

Aims:The importance of early life factors in determining health in later adulthood is increasingly recognized. This study evaluated the association of adverse childhood experiences (ACEs) with cardiovascular magnetic resonance (CMR) phenotypes. Methods and results:UK Biobank participants who had completed CMR and the self-reported questionnaire on traumatic childhood experiences were included. Images were analysed using automated pipelines to extract measures of left and right ventricular (LV and RV) structure and function, myocardial character, and arterial compliance. Multivariable linear regression was used to estimate the association of childhood adversity with CMR phenotypes adjusting for age, sex, deprivation, education, obesity, smoking, alcohol intake, exercise level, diabetes, hypertension, and hypercholesterolaemia. Amongst 30 814 participants analysed, 6023 (19.5%) experienced physical abuse, 2746 (8.9%) sexual abuse, 4685 (15.2%) emotional abuse, 6822 (22.1%) emotional neglect, and 4534 (14.7%) physical neglect. Except for physical abuse, women reported greater rates of childhood adversity than men. Collectively, all types of childhood adversity were associated with smaller LV and RV volumes, greater LV mass, a concentric pattern of LV remodelling, poorer LV and RV function, lower aortic compliance, and greater arterial stiffness. Sexual abuse was associated with unhealthy CMR phenotypes in age- and sex-adjusted models, but these relationships were attenuated in fully adjusted models. Physical neglect had the most prominent pattern of adverse cardiovascular remodelling. Conclusion:ACEs were associated with unhealthy cardiovascular remodelling in adulthood, independent of traditional cardiovascular risk factors. These findings support the consideration of early life factors in cardiovascular disease risk assessment.

OBJECTIVE:Further to previous development and internal validation of the Barts Surgical Infection Risk (B-SIR) tool, this study sought to explore the external validity of the B-SIR tool and compare it with the Australian Clinical Risk Index (ACRI), and the Brompton and Harefield Infection Score (BHIS). STUDY DESIGN AND SETTING:This multi-centre retrospective analysis of prospectively collected local data included adult (age ≥18 years) patients undergoing cardiac surgery between January 2018 and December 2019. Pre-pandemic data were 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 the Hosmer-Lemeshow test and calibration plots. RESULTS:In total, 6022 patients from three centres were included in the complete case analysis. The mean age was 66 years, 75% were men and 3.19% developed a surgical site infection (SSI). The B-SIR tool had an area under the curve (AUC) of 0.686 [95% confidence interval (CI) 0.649-0.723], similar to the developmental study (AUC=0.682, 95% CI 0.652-0.713). This was significantly higher than the BHIS AUC of 0.610 (95% CI 0.045-0.109; P<0.001) and the ACRI AUC of 0.614 (95% CI 0.041-0.103; P<0.001). After recalibration using a correction factor, the B-SIR tool gave accurate risk predictions (Hosmer-Lemeshow test P=0.423). The multiple imputation result (AUC=0.676, 95% CI 0.639-0.712) was similar to development data, and higher than the ACRI and BHIS. CONCLUSION:External validation indicated that the B-SIR tool predicted SSI after cardiac surgery better than the ACRI and BHIS. This suggests that the B-SIR tool could be useful for use in routine practice.

Aims We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases. Methods and results In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively. Conclusions We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.

Sleep duration and chronotype have been associated with increased morbidity and mortality. We assessed for associations between sleep duration and chronotype on cardiac structure and function. UK Biobank participants with CMR data and without known cardiovascular disease were included. Self-reported sleep duration was categorized as short (<7 h/d), normal (7-9 h/d) and long (>9 h/d). Self-reported chronotype was categories as "definitely morning" or "definitely evening." Analysis included 3903 middle-aged adults: 929 short, 2924 normal and 50 long sleepers; with 966 definitely-morning and 355 definitely-evening chronotypes. Long sleep was independently associated with lower left ventricular (LV) mass (-4.8%, P = 0.035), left atrial maximum volume (-8.1%, P = 0.041) and right ventricular (RV) end-diastolic volume (-4.8%, P = 0.038) compared to those with normal sleep duration. Evening chronotype was independently associated with lower LV end-diastolic volume (-2.4%, P = 0.021), RV end-diastolic volume (-3.6%, P = 0.0006), RV end systolic volume (-5.1%, P = 0.0009), RV stroke volume (RVSV -2.7%, P = 0.033), right atrial maximal volume (-4.3%, P = 0.011) and emptying fraction (+1.3%, P = 0.047) compared to morning chronotype. Sex interactions existed for sleep duration and chronotype and age interaction for chronotype even after considering potential confounders. In conclusion, longer sleep duration was independently associated with smaller LV mass, left atrial volume and RV volume. Evening chronotype was independently associated with smaller LV and RV and reduced RV function compared to morning chronotype. Sex interactions exist with cardiac remodeling most evident in males with long sleep duration and evening chronotype. Recommendations for sleep chronotype and duration may need to be individualized based on sex.

ObjectiveTo examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.MethodsCOVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32–395) of prospective follow-up.ResultsNon-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.ConclusionsIndividuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.

Aims Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.Methods and results Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.Conclusions Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.

Background: Advances in coronary computed tomography angiography (CCTA) reconstruction algorithms are expected to enhance the accuracy of CCTA plaque quantification. We aim to evaluate different CCTA recon-struction approaches in assessing vessel characteristics in coronary atheroma using intravascular ultrasound (IVUS) as the reference standard. Methods: Matched cross-sections (n = 7241) from 50 vessels in 15 participants with chronic coronary syndrome who prospectively underwent CCTA and 3-vessel near-infrared spectroscopy-IVUS were included. Twelve CCTA datasets per patient were reconstructed using two different kernels, two slice thicknesses (0.75 mm and 0.50 mm) and three different strengths of advanced model-based iterative reconstruction (IR) algorithms. Lumen and vessel wall borders were manually annotated in every IVUS and CCTA cross-section which were co-registered using dedicated software. Image quality was sub-optimal in the reconstructions with a sharper kernel, so these were excluded. Intraclass correlation coefficient (ICC) and repeatability coefficient (RC) were used to compare the estimations of the 6 CT reconstruction approaches with those derived by IVUS. Results: Segment-level analysis showed good agreement between CCTA and IVUS for assessing atheroma volume with approach 0.50/5 (slice thickness 0.50 mm and highest strength 5 ADMIRE IR) being the best (total atheroma volume ICC: 0.91, RC: 0.67, p < 0.001 and percentage atheroma volume ICC: 0.64, RC: 14.06, p < 0.001). At lesion-level, there was no difference between the CCTA reconstructions for detecting plaques (accuracy range: 0.64-0.67; p = 0.23); however, approach 0.50/5 was superior in assessing IVUS-derived lesion characteristics associated with plaque vulnerability (minimum lumen area ICC: 0.64, RC: 1.31, p < 0.001 and plaque burden ICC: 0.45, RC: 32.0, p < 0.001). Conclusion: CCTA reconstruction with thinner slice thickness, smooth kernel and highest strength advanced IR enabled more accurate quantification of the lumen and plaque at a segment-, and lesion-level analysis in coronary atheroma when validated against intravascular ultrasound. Clinicaltrials.gov (NCT03556644)

AbstractAimsTo evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.Methods and resultsThe analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.ConclusionGreater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.

Patients with classic low-flow low-gradient (cLFLG) aortic stenosis (AS) have a poor prognosis but still benefit from aortic valve replacement. There is a paucity of evidence to guide the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This study compared procedural and midterm outcomes in patients with cLFLG AS between TAVR and SAVR. Patients with cLFLG AS, defined as an aortic valve area ≤1 cm2, mean gradient <40 mm Hg, and left ventricular ejection fraction <50%, were selected from a single center between 2015 and 2020. Inverse probability weighting and regression were used to adjust for differences in baseline characteristics, the nonrandom assignment of treatment modalities, and procedural differences. The primary end point was all-cause mortality. A total of 322 patients (220 TAVR and 102 SAVR) were included. At a follow-up of 4.4 ± 1.5 years, the adjusted hazard ratio (HR) for mortality after inverse probability weighting with SAVR was 0.66, 95% confidence interval (CI) 0.31 to 1.35; p = 0.24. Worse renal function at baseline (per 10 ml/min/m2 increase HR 0.92, 95% CI 0.84 to 1.00, p = 0.04) and multiple valve interventions (HR 5.39, 95% CI 2.62 to 11.12, p <0.001) independently predicted mortality. There was no difference in stroke and permanent pacemaker implantation, but the rates of renal replacement therapy were higher among the SAVR cohort: 13.7% versus 0%; p <0.001. In conclusion, among patients with cLFLG AS, there was no difference in midterm mortality between TAVR and SAVR, supporting the use of either treatment. However, in patients with poor renal function or at risk of renal failure, TAVR may be the preferred option.

Objectives To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer. Methods Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics. Results We studied 18 714 participants (67% women, age: 62 (IQR: 57–66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92–3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34–2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk. Conclusions Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.

Introduction Obesity is a rising public health crisis and a major risk factor for heart failure (HF). However, underlying mechanisms are incompletely understood. In this study, we investigate longitudinal associations of obesity with incident HF and cardiovascular imaging phenotypes in the UK Biobank (UKB). Importantly, we use cardiovascular magnetic resonance (CMR) to investigate potential mechanisms driving the obesity-HF relationships. Methods The UKB cohort comprises over half a million individuals recruited from across the UK between 2006–2010. The UKB imaging study, which includes CMR, commenced in 2015 with plan to scan a random 20% subset of the original cohort. We defined obesity using body mass index (BMI) and waist-to-hip-ratio (WHR) measured at baseline recruitment. Incident HF events were identified through linked Hospital Episode Statistics data (censor date December 2021). CMR scans were analysed using an automated pipeline. We used Cox proportional hazard regression models adjusted for potential confounders to estimate the associations of BMI and WHR with incident HF in the whole sample. We used linear regression to characterise obesity (BMI, WHR) associations with CMR phenotypes. Finally, we used multiple mediation analysis to define the role of obesity-related cardiac remodelling in driving its associations with incident HF, independent of cardiometabolic diseases (diabetes, hypertension, high cholesterol). Results In 491,606 UK Biobank participants (mean age 56.6 years, 54.3% women) over 12.2±0.9 years of prospective follow-up, higher BMI [HR 1.34 (1.32, 1.37)] and WHR [HR 1.30 (1.30, 1.36)] were associated with a greater hazard of HF. In the subset of participants with CMR (n=31,107), greater obesity was associated with adverse left ventricular (LV) structure (higher LV mass, greater concentricity), poorer LV global functional index, and lower myocardial native T1. In multiple mediation analysis, hypertension had an important role in mediating the associations of obesity with incident HF. Adverse LV remodelling (higher LV mass, greater concentricity) were also major mediators of the obesity-HF associations, independent of cardiometabolic disease. Notably, higher native T1 (indicated greater myocardial fibrosis) mediated a significant fraction of the relationship between obesity and incident HF. Given that in the whole cohort greater obesity was related to lower native T1, this observation may indicate different stages of progression in obesity-related cardiac remodelling. Conclusion Our findings demonstrate the association of obesity with a greater risk of HF and adverse alterations of LV structure, function, and myocardial character. Importantly, we highlight the role of specific adverse cardiovascular remodelling patterns in driving obesity-HF associations. Thus, our findings highlight the growing public health importance of obesity as a driver of HF and propose novel channels for dedicated mechanistic research. Conflict of Interest None

Background Volumetric intravascular ultrasound (IVUS) analysis is currently performed at a fixed frame interval, neglecting the cyclic changes in vessel dimensions occurring during the cardiac cycle that can affect the reproducibility of the results. Analysis of end-diastolic (ED) IVUS frames has been proposed to overcome this limitation. However, at present, there is lack of data to support its superiority over conventional IVUS. Objectives The present study aims to compare the reproducibility of IVUS volumetric analysis performed at a fixed frame interval and at the ED frames, identified retrospectively using a novel deep-learning methodology. Methods IVUS data acquired from 97 vessels were included in the present study; each vessel was segmented at 1 mm interval (conventional approach) and at ED frame twice by an expert analyst. Reproducibility was tested for the following metrics; normalized lumen, vessel and total atheroma volume (TAV), and percent atheroma volume (PAV). Results The mean length of the analyzed segments was 50.0 +/- 24.1 mm. ED analysis was more reproducible than the conventional analysis for the normalized lumen (mean difference: 0.76 +/- 4.03 mm(3) vs. 1.72 +/- 11.37 mm(3); p for the variance of differences ratio < 0.001), vessel (0.30 +/- 1.79 mm(3) vs. -0.47 +/- 10.26 mm(3); p < 0.001), TAV (-0.46 +/- 4.03 mm(3) vs. -2.19 +/- 14.39 mm(3); p < 0.001) and PAV (-0.12 +/- 0.59% vs. -0.34 +/- 1.34%; p < 0.001). Results were similar when the analysis focused on the 10 mm most diseased segment. The superiority of the ED approach was due to a more reproducible detection of the segment of interest and to the fact that it was not susceptible to the longitudinal motion of the IVUS probe and the cyclic changes in vessel dimensions during the cardiac cycle. Conclusions ED IVUS segmentation enables more reproducible volumetric analysis and quantification of TAV and PAV that are established end points in longitudinal studies assessing the efficacy of novel pharmacotherapies. Therefore, it should be preferred over conventional IVUS analysis as its higher reproducibility is expected to have an impact on the sample size calculation for the primary end point.

Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known. The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort. The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall. From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01). This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding.

ObjectiveTo examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.MethodsCompeting risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7–12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight–MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.Results258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10–5) and attenuation to the null above this threshold. The birth weight–MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight–mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).ConclusionsLower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.

BACKGROUND Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known. OBJECTIVES The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort. METHODS The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall. RESULTS From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse wasmore frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01). CONCLUSIONS This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding. (J Am Coll Cardiol Img 2022;15:1856-1866) (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 μm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.