Search

Aims The aim of this study is to develop and validate a deep learning (DL) methodology capable of automated and accurate segmentation of intravascular ultrasound (IVUS) image sequences in real-time. Methods and results IVUS segmentation was performed by two experts who manually annotated the external elastic membrane (EEM) and lumen borders in the end-diastolic frames of 197 IVUS sequences portraying the native coronary arteries of 65 patients. The IVUS sequences of 177 randomly-selected vessels were used to train and optimise a novel DL model for the segmentation of IVUS images. Validation of the developed methodology was performed in 20 vessels using the estimations of two expert analysts as the reference standard. The mean difference for the EEM, lumen and plaque area between the DL-methodology and the analysts was ≤0.23mm2 (standard deviation ≤0.85mm2), while the Hausdorff and mean distance differences for the EEM and lumen borders was ≤0.19 mm (standard deviation≤0.17 mm). The agreement between DL and experts was similar to experts' agreement (Williams Index ranges: 0.754–1.061) with similar results in frames portraying calcific plaques or side branches. Conclusions The developed DL-methodology appears accurate and capable of segmenting high-resolution real-world IVUS datasets. These features are expected to facilitate its broad adoption and enhance the applications of IVUS in clinical practice and research.

We hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91–0.99), sensitivity 0.84 (0.7–0.93) and specificity 0.95 (0.85–0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17–0.69) and specificity 0.95 (0.85–0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.

This study sought to identify patients with repaired tetralogy of Fallot (rTOF) at high risk of death and malignant ventricular arrhythmia (VA).To date there is no robust risk stratification scheme to predict outcomes in adults with rTOF.Consecutive patients were prospectively recruited for late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to define right and left ventricular (RV, LV) fibrosis in addition to proven risk markers.The primary endpoint was all-cause mortality. Of the 550 patients (median age 32 years, 56% male), 27 died (mean follow-up 6.4 ± 5.8; total 3,512 years). Mortality was independently predicted by RVLGE extent, presence of LVLGE, RV ejection fraction ≤47%, LV ejection fraction ≤55%, B-type natriuretic peptide ≥127 ng/L, peak exercise oxygen uptake (V0We present a score integrating multiple appropriately weighted risk factors to identify the subgroup of patients with rTOF who are at high annual risk of death who may benefit from targeted therapy.

Background: Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy, but human measurement is prone to variability. We developed an automated machine learning algorithm for MWT measurement and compared precision (reproducibility) with that of 11 international experts, using a dataset of patients with hypertrophic cardiomyopathy. Methods: 60 adult patients with hypertrophic cardiomyopathy, including those carrying hypertrophic cardiomyopathy gene mutations, were recruited at three institutes in the UK from August, 2018, to September, 2019: Barts Heart Centre, University College London Hospital (The Heart Hospital), and Leeds Teaching Hospitals NHS Trust. Participants had two cardiovascular magnetic resonance scans (test and retest) on the same day, ensuring no biological variability, using four cardiac MRI scanner models represented across two manufacturers and two field strengths. End-diastolic short-axis MWT was measured in test and retest by 11 international experts (from nine centres in six countries) and an automated machine learning method, which was trained to segment endocardial and epicardial contours on an independent, multicentre, multidisease dataset of 1923 patients. Machine learning MWT measurement was done with a method based on solving Laplace's equation. To assess test–retest reproducibility, we estimated the absolute test–retest MWT difference (precision), the coefficient of variation (CoV) for duplicate measurements, and the number of patients reclassified between test and retest according to different thresholds (MWT >15 mm and >30 mm). We calculated the sample size required to detect a prespecified MWT change between pairs of scans for machine learning and each expert. Findings: 1440 MWT measurements were analysed, corresponding to two scans from 60 participants by 12 observers (11 experts and machine learning). Experts differed in the MWT they measured, ranging from 14·9 mm (SD 4·2) to 19·0 mm (4·7; p

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Myocardial extracellular volume (ECV) increases with fibrosis, oedema or infiltration. ECV by CMR predicts all-cause and cardiovascular mortality in severe AS after valve intervention. Previous studies have shown that ECV can be reliably quantified by computed tomography (ECVCT), but these studies have not differentiated between ECV elevation due to fibrosis or cardiac amyloid deposition (13-16% of patients with severe AS). Purpose We hypothesised that ECVCT quantification, performed as part of a transcatheter aortic valve implantation (TAVI) work-up CT, predicts survival in patients with severe AS without cardiac amyloid (lone AS). Methods Patients aged ≥75, with severe AS, referred for TAVI at Barts Heart Centre (as part of ATTRact-AS (NCT03029026)) underwent CT as part of their clinical work-up. All patients had 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy and those with a positive result were excluded. CT was performed on a 128-slice dual-source 3rdgeneration scanner (Siemens Somatom FORCE) and ECVCT was acquired during the TAVI work-up CT using additional pre- and 3-minute post-contrast ‘axial shuttle mode’ acquisitions (no additional contrast). ECVCT was calculated from the Hounsfield units (HU) and a venous haematocrit (HCT): ECVCT = (1-HCT) x (ΔHUmyo/ΔHUblood). Results Following exclusion of 16 patients with cardiac uptake on DPD, 93 patients (41% male, aged 85 ± 5 years) were included in the study. All patients had severe AS (AV Vmax 4.12 ± 0.63m/s, mean AV gradient 42 ± 14mmHg, AVA 0.71 ± 0.23cm2). The mean HCT was 0.38 ± 0.04 and total dose-length product for additional research scans was 364 ± 41 mGy.cm. 76 patients (82%) underwent TAVI. ECVCT was 32 ± 3% in the entire cohort, which we then split into those with a ‘higher’ ECVCT (>34%, n = 23, representing the highest quartile) and those with a ‘lower’ ECVCT (≤34%, n = 70, representing the lower quartiles). Over a median follow-up of 25 months (IQR 17-34 months) there were 27 deaths (29%), of whom 11 did not undergo TAVI (41%). There were 10 deaths in the 23 patients (44%) with a higher ECVCT, compared to 17 in the 70 patients (24%) with a lower ECVCT (p = 0.03, figure 1). This mortality difference remained significant when those patients who did not undergo TAVI were excluded (p = 0.03). Conclusions Myocardial fibrosis quantified by ECVCT is associated with a significantly worse prognosis in lone AS, even after patients with AS-amyloid are excluded. ECVCT can be performed as a simple addition to the TAVI work-up CT and provides additional prognostic information. Abstract Figure.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Quantitative myocardial perfusion mapping using Cardiac Magnetic Resonance (CMR) imaging is used for evaluation of ischaemia in the context of native vessel coronary disease, but its diagnostic performance in patients with grafts is not well established. Perfusion defects are often detected in these patients, but whether these are a consequence of a technical limitation (delayed contrast arrival from graft conduits) or a true reflection of reduced myocardial blood flow is unclear. Methods 39 patients undergoing stress perfusion CMR with previous coronary artery bypass graft (CABG) surgery, unobstructed left internal mammary artery (LIMA) grafts to the left anterior descending (LAD) artery on coronary angiography and no CMR evidence of prior LAD infarction were included. Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were evaluated with quantitative perfusion mapping and the factors determining MBF in the LIMA-LAD territory (AHA segments 1,2,7,8,13,14), including the impact of delayed contrast arrival through the LIMA graft were evaluated. Results In 28 out of 39 cases a myocardial perfusion defect was reported on visual assessment in LIMA-LAD myocardial territory, despite the presence of unobstructed LIMA graft and no LAD infarction. Chronic total occlusion (CTO) of the native LAD was an independent predictor of stress MBF (B=-0.36, p =0.027) and the strongest predictor of MPR (B=-0.55, p 0.005) within the LIMA-LAD myocardial territory after adjusting for age, left ventricular (LV) ejection fraction, and presence of diabetes. CTO of the native LAD was associated with a reduction in stress MBF in the basal myocardial segments (-0.57ml/g/min, p = 0.002) but had no effect on the MBF of apical segments (-0.31ml/g/min, p = 0.084). Increasing the maximum value for allowable arterial delay (TA) of contrast in the quantitative mapping algorithm resulted in a small increase in myocardial blood flow in the LIMA-LAD territory both at stress (0.07 ± 0.08ml/g/min, p Conclusions Perfusion defects detected in LIMA-LAD subtended territories are common despite graft patency. These defects are likely to represent genuine reduction in MBF, resulting from native LAD coronary occlusion. Prolonged contrast transit time associated with LIMA grafts results in small underestimation of MBF as measured by quantitative CMR perfusion mapping, but does not account for the degree of MBF reduction seen in these patients. Figure 1. Study patient with unobstructed LIMA to LAD graft and evidence of inducible perfusion defect in LIMA-LAD territories. (A): First pass perfusion CMR imaging. (B): Perfusion mapping showing reduced stress MBF in mid antero-septum (0.85ml/g/min) compared to the apical septum (1.65ml/g/min). (C): Late gadolinium enhancement showing no evidence of previous infarction. (D,E): Coronary angiography demonstrating unobstructed LIMA graft (D) and anastomosis site (E). Abstract Figure 1.

Background Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years’ follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): I have received a research fellowship grant from the UK based charity Cardiac Risk in the Young Objectives We investigated the effect of long-term exercise and sex on left ventricular (LV) geometry in a large group of female and male masters athletes. Background Studies assessing LV geometry in masters athletes are scarce. Methods Different types of LV geometry were identified according to echocardiography-derived relative wall thickness (RWT) and left ventricular mass (LVM) values as per international guidelines. 4 groups were formed: normal (normal LVM/normal RWT), concentric hypertrophy (increased LVM/increased RWT), eccentric hypertrophy (increased LVM/normal RWT), and concentric remodeling (normal LVM/increased RWT). Results A total of 277 healthy, elite, caucasian endurance masters athletes (65% female; mean age54.8 ± 7.7 years) were assessed. The athletes were exercising for a mean 32 ± 11.7 years and have completed a median 70 competitions including a median 13 marathon-type competitions. Females exhibited lower absolute LVM (127.7 ± 30.31g vs 196.57 ± 45.0g, p < 0.001), indexed LVM (76.8 ± 18.0 g/m2 vs. 103.6 ± 22.7 g/m2; p < 0.001), RWT (0.36 ± 0.07 vs. 0.42 ± 0.08; p < 0.001) and absolute LV end-diastolic dimension (LVEDD) (46.3 ± 4.1 mm vs 50.1 ± 5.11 mm, p < 0.001) but greater indexed LVEDD (27.7 ± 2.7mm/m2 vs 26.5 ± 2.7 mm/m2, p < 0.001) compared with male athletes. Most female athletes showed normal LV geometry (72% vs 38% in male athletes, P Conclusions A sex-specific response to chronic exercise is observed. Male masters athletes exhibit significantly more frequently abnormal LV geometry with concentric LV remodeling and/or concentric hypertrophy. Cohort characteristics Male masters athletes N = 97 Female masters athletes N = 180 P value Age (years) 55.0 ± 9.0 54.7 ± 6.9 0.68 Years of exercise 32.0 ± 12.8 33.3 ± 11.1 0.14 LV Mass (g) 127.7 ± 30.31 196.57 ± 45.0

Funding Acknowledgements Type of funding sources: None. Background Staging of Fabry disease (FD) cardiomyopathy uses multiparametric cardiac MRI. Advanced disease is characterized by left ventricular hypertrophy (LVH), myocardial inflammation/oedema (high native T2 mapping) and/or fibrosis (late gadolinium enhancement, LGE). Pre-LVH involvement has been described and includes myocardial sphingolipid storage (low native T1 mapping), impaired LV global longitudinal strain (GLS) and microvascular disease/dysfunction (low stress myocardial blood flow, MBF, in perfusion mapping). We aimed to define (1) the early myocardial phenotype prior to T1 lowering/pre-storage and (2) the stages of cardiac involvement in FD. Methods FD patients and age, sex and heart rate matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR (cines, GLS, pre-contrast T1 and T2 mapping, adenosine stress perfusion mapping [for MBF] and LGE). Results 114 Fabry patients (46 ± 13 years, 61% female, 37% [n = 72] had LVH) and 76 controls (49 ± 15 years, 50% female) were included. FD with vs without LVH in brief and as expected, FD with LVH had significantly (p FD pre-LVH low T1 vs pre-LVH normal T1: low T1 patients (32/72, 44%) had higher LV mass index (67 ± 14 vs 59 ± 10g/m2, P = 0.011), maximum Q wave amplitude (2[1-2] vs 1[1-2]mm, P FD pre-LVH normal T1 vs healthy controls: normal T1 pre-LVH Fabry patients (40/72, 56%) had reduced GLS (-18 ± 2 vs -20 ± 2%, P Conclusion Prior staging of Fabry cardiomyopathy included a pre-LVH stage (accumulation/storage) and two LVH stages (hypertrophy and inflammation; fibrosis and impairment). Here we define an even earlier stage, pre-LVH pre-detectable storage, defined by microvascular dysfunction, impaired GLS and altered atrial depolarization and ventricular repolarization intervals (see Figure). Abstract Figure. Proposed stages of cardiac involvement

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by a Clinical Training Research Fellowship (K. Knott) from the British Heart Foundation and directly and indirectly from the Biomedical Research Centre at University College London Hospitals and Barts Heart Centre. Background Cardiovascular magnetic resonance (CMR) with automated inline perfusion mapping permits rapid fully automated non-invasive myocardial blood flow (MBF, ml/g/min). Understanding the microvascular component of MBF would help optimize epicardial coronary artery disease detection and potentially serve as an independent diagnostic / therapeutic target. Purpose To explore MBF influences at stress and rest in patients with unobstructed epicardial coronary arteries. Methods 242 participants (mean age 56.9 years) from 5 European centers with unobstructed epicardial coronary arteries and no myocardial scar underwent adenosine vasodilator perfusion mapping at stress and rest. The factors influencing MBF were determined using univariate and multivariate linear regression analyses. Results Mean rest perfusion was 0.91+/-0.24ml/g/min. Rest perfusion was higher in females (0.97+/-0.22ml/g/min vs 0.83 +/- 0.24ml/g/min) and lower in patients on beta blockers. Mean stress MBF was 2.53+/-0.82ml/g/min. Factors independently associated with reduced stress MBF were increasing age, diabetes, increasing left ventricular mass (LVMi) and the use of beta blockers. The predicted stress MBF can be obtained from the equation MBF = 2.66–0.015(age-60)–0.013(LVMi-57)-0.405(diabetes)–0.365(beta blocker). This means stress MBF falls 10% over 19 years and that diabetes drops the MBF by the equivalent of being 27 years older. These changes are large: for example, a 70-year-old diabetic would have 30% lower stress MBF than a 35 year-old non-diabetic. Conclusions In the absence of obstructive epicardial coronary disease, stress MBF falls with age, diabetes, increased LV mass and beta-blockers. These data may help develop normal reference ranges, input to other modelling (eg CT FFR), and they advance perfusion mapping as a measure of microvascular function. Abstract Figure. Summary of the determinants of perfusion

Background: Survival in transfusion dependent thalassemia is closely linked to iron overload with severe cardiac iron causing heart failure. MRI guided chelation improves survival in high income countries. We explored the use of rapid MRI to guide therapy in a Lower Middle Income Country (LMIC), India, via locally organized thalassemia patient medical camps. Methods: Rapid cardiac MRI (rCMR) was implemented at two sites with clinical assessment and therapy recommendations based on rCMR findings. Investigations and clinical reassessment were repeated at 13 months. Findings: The baseline visit was attended by 103 patients, the second by 86. Average time of scanning was 10 minutes. At baseline 29% had a cardiac T2* = 17ms). At 13 months more patients were taking 2 oral chelators (21% to 37%, p

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Barts Cardiovascular Biomedical Research Centre onbehalf The Marathon Study Consortium Introduction Cardiovascular function depends on the inter-relation between heart and vasculature. The contribution of aorta and peripheral vessels to the total systolic load of the left ventricle (LV) can be represented respectively by a "pulsatile" and a "resistive" component. We sought to understand their interrelation by exploring how LV remodelling occurred with altered load associated with an external stimulus (training). Methods: 237 untrained healthy male and female subjects volunteering for their first-time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided into 4 groups according to the variation (positive versus null or negative) in Total Arterial Compliance Index (TACi), representing the pulsatile component of the LV load, and in Systemic Vascular Resistance Index (SVRI), representing the resistive component of the LV load. Results: 138runners (age 21-69 years; F: 51%) completed the race. Data are reported for each variable as Δ mean [95% Confidence Interval]. In the whole cohort, training was associated with a small increase in LV mass index (+3g/m2, [0, 6 g/m2]), indexed LV end-diastolic volume (EDVi) (+3ml/m2, [-2, 5 3ml/m2]), in LV mass/LVEDV ratio (+0.02g/ml, [0.00, 0.04 g/ml]) and in TACi (+0.02ml/m2, [0.02, 0.38 ml/m2]). SVRi mildly fell (-43dyn·s/cm2[-103, 17dyn·s/cm2]). TACi increase was associated with LVEDVi increase and no change in LV mass/EDV (eccentric remodelling). On the other hand, both TACi reduction and SVRi increase were associated with increase in LV mass/EDV and no significant change in LVEDVi (concentric remodelling). A similar increase in LV mass was observed in all groups. See Table. Conclusion: Cardiac remodelling observed after mild, medium term, unsupervised training seems to be related to the modifications of aorta and peripheral vessels. In particular, a reduction in pulsatile load seems associated with eccentric LV remodelling, while an increase in both pulsatile and resistive with concentric LV remodelling. Further research is needed to understand the interaction between TACi and SVRi. Table 1 LV EDVi (ml/m2) LV mass index (g/m2) LV mass/EDV TACi increase (n = 75) +4 [0, 9] +3 [0, 7] 0 [-0.03, 0.03] TACi decrease (n = 62) -1 [-6, 4] +3 [0, 8] 0.04 [0.01, 0.07] SVRi increase (n = 63) 0 [-4,4] +3 [0, 7] +0.03 [0, 0.06] SVRi decrease (n = 73) +3 [-3, 7] +3 [-1, 6] +0.01 [-0.02, 0.04]

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospital Biomedical Research Centre Background In people with obesity, bariatric surgery reduces mortality, heart failure and coronary disease, improving metabolic (blood sugar, lipid profile, inflammation) and cardiovascular (diastolic/systolic function, filling pressure, cardiac remodelling) parameters. Myocardial microvascular function is a candidate causal link of metabolic to structural cardiac abnormalities. Purpose We hypothesised that bariatric surgery could improve myocardial microvascular and mechanical function in both those with and without diabetes. Methods Before and six months after bariatric surgery, 24 subjects with obesity were assessed with haematology, biochemistry and advanced CMR (cines, vasodilator adenosine stress and rest fully-automated quantitative perfusion mapping, tissue-tracking (CVI42, post processing). Results. Mean age was 49± 12 years, 35%(8) were male, 63%(15), had hypertension, 17 (71%) had diabetes. Surgery resulted in decreases in BMI (44 ± 7 to 34 ± 6 kg/m2 p = 0.0001) and HbA1c (57 ± 16 to 42 ± 9mmol/mol p = 0.0001). EF% and absolute LV end-diastolic volumes remained unchanged, but mass regressed and myocardial contraction fraction (ratio of stroke volume and LV volume) increased (see Table). There were also strain improvements (radial 35 ± 8.8 to 37.3 ± 8.7 %p = 0.029) (circumferential -19.8 ± 2.3 vs -20.7 ± 3% p = 0.017), although longitudinal did not improve (-16.3 ± 3.2 to -15.9 ± 3% p = 0.25). Myocardial perfusion significantly improved (stress myocardial blood flow, MBF 2.35 ± 0.71 to 2.80 ± 0.98 ml/g/min p = 0.008; myocardial perfusion reserve MPR 2.47 ± 0.78 to 2.97 ± 0.95 p = 0.005). Improvement in stress MBF and MPR from pre-operative to post-operative was higher in the non-diabetics (n = 7 (29%)) than the diabetics (n = 17 (71%)) (stress MBF: 1.15 ± 1.00 vs 0.16 ± 0.39ml/g/min p = 0.002) MPR: (1.09 ± 0.73 vs 0.25 ± 0.66 p = 0.011). Conclusion At 6 months, bariatric surgery results in beneficial myocardial remodelling and substantial improvements in myocardial microvascular function. These improvements occur most in those without diabetes suggesting that there may be reversible and irreversible components to microvascular dysfunction. Perfusion and strain variables Variable Pre-op (n = 24) Post-op (n = 24) p-value LVEDV (ml) 163 ± 28 161 ± 29 0.64 EF (%) 70 ± 8 70 ± 7 0.78 Stroke volume (ml) 113 ± 19 111 ± 21 0.6 LV Mass (g) 117 ± 25 103 ± 21 0.001 Myocardial contraction fraction 94 ± 14 105 ± 14 0.001 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction Abstract Figure.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Guy"s and St Thomas" Charity University College London Hospitals Biomedical Research Centre Background Obesity and cardiovascular disease are associated, but the relationship is poorly understood. Myocardial perfusion, metabolic derangement and lipotoxicity appear adversely associated in many scenarios (myocardial injury, diastolic dysfunction, diabetes). Altered perfusion (by PET) predicts outcome, and it is hypothesised that perfusion derangement is part of causality for cardiac disease and adverse outcomes. Purpose To assess the presence and pattern of myocardial microvascular dysfunction in patients with obesity (scheduled for bariatric surgery) using stress quantitative perfusion mapping. Methods 38 subjects with obesity planned to undergo bariatric surgery and 38 age and sex matched healthy volunteers (no diabetes, no hypertension) underwent anthropometry, biochemistry and CMR at 1.5T (Siemens) with cine imaging, stress (adenosine 140-210 mcg/kg/min) and rest fully-automated quantitative perfusion mapping. Results Bariatric patients had a higher BMI (44 ± 6.4 vs 26.5 ± 4kg/m2 p = 0.001); 58%(22) were diabetic and 58%(22) had hypertension. Bariatric patients had higher absolute but lower indexed end-diastolic volumes, and overall higher ejection fractions (+5%) (see Table). Rest myocardial blood flow (MBF) in bariatric patients was the same (1.00 ± 0.3 vs 0.88 ± 0.24 p = 0.052), but stress perfusion results were significantly lower both for stress MBF (2.35 ± 0.69 vs 2.93 ± 0.76ml/g/min p = 0.001) and myocardial perfusion reserve (MPR 2.48 ± 0.82 vs 3.4 ± 0.81ml/g/min p = 0.0001). Although this was transmural, the endocardial stress MBF was particularly negatively affected in the bariatric cohort compared to controls (endocardial MBF 2.16 ± 0.65 vs 2.82 ± 0.73ml/g/min, p = 0.0001 vs epicardial MBF: 2.52 ± 0.76 vs 3.06 ± 0.79 p = 0.003), meaning there was an increased endo-epicardial stress MBF gradient in bariatric patients (0.87 ± 0.12 vs 0.92 ± 0.07 p = 0.03). Conclusion Compared to healthy controls, patients with obesity have abnormal myocardial stress perfusion with reduced global perfusion, perfusion reserve and an increased transmyocardial perfusion gradient. Table - myocardial perfusion parameters Category Bariatric patients n = 38 Controls n = 38 p value Age (years) 48 ± 11 45 ± 13 0.25 n male (%) 12 (32%) 10 (36%) 0.32 LVEDV (ml) 168 ± 37 149 ± 31 0.017 LVEDVi (ml/m2) 70.4 ± 12.3 78.8 ± 12.1 0.004 LV Mass (g) 116 ± 31 99 ± 28 0.019 EF (%) 70 ± 8 65 ± 5 0.002 LVEDV - left ventricular end-diastolic volume, EF - ejection fraction

Background: Measurement of myocardial T1 is increasingly incorporated into standard cardiovascular magnetic resonance (CMR) protocols, however accuracy may be reduced in patients with metallic cardiovascular implants. Measurement is feasible in segments free from visual artifact, but there may still be off-resonance induced error.Aim: To quantify off-resonance induced T1 error in patients with metallic cardiovascular implants, and validate a method for error correction for a conventional MOLLI pulse sequence.Methods: Twenty-four patients with cardiac implantable electronic devices (CIEDs: 46% permanent pacemakers, PPMs; 33% implantable loop recorders, ILRs; and 21% implantable cardioverter-defibrillators, ICDs); and 31 patients with aortic valve replacement (AVR) (45% metallic) were studied. Paired mid-myocardial short-axis MOLLI and single breath-hold off-resonance field maps were acquired at 1.5 T. T1 values were measured by AHA segment, and segments with visual artifact were excluded. T1 correction was applied using a published relationship between off-resonance and T1. The accuracy of the correction was assessed in 10 healthy volunteers by measuring T1 before and after external placement of an ICD generator next to the chest to generate off-resonance.Results: T1 values in healthy volunteers with an ICD were underestimated compared to without (967 ± 52 vs. 997 ± 26 ms respectively, p = 0.0001), but were similar after correction (p = 0.57, residual difference 2 ± 27 ms). Artifact was visible in 4 ± 12, 42 ± 31, and 53 ± 27% of AHA segments in patients with ILRs, PPMs, and ICDs, respectively. In segments without artifact, T1 was underestimated by 63 ms (interquartile range: 7–143) per patient. The greatest error for patients with ILRs, PPMs and ICDs were 79, 146, and 191 ms, respectively. The presence of an AVR did not generate T1 error.Conclusion: Even when there is no visual artifact, there is error in T1 in patients with CIEDs, but not AVRs. Off-resonance field map acquisition can detect error in measured T1, and a correction can be applied to quantify T1 MOLLI accurately.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation onbehalf AS-Amyloidosis consortium Background The coexistence of severe aortic stenosis (lone AS) and transthyretin cardiac amyloidosis (lone amyloidosis) is common, but the resultant AS-amyloidosis phenotype is unclear. Purpose We characterised AS-amyloidosis, hypothesizing that the dual insult of AS-amyloidosis results is a severe phenotype. Methods We compared four cohorts with deep phenotyping: 81 older age controls, 359 lone AS, 36 AS-amyloidosis (Perugini grade 2 and 3) and 107 lone amyloidosis (Perugini grade 2 and 3). Results AS-amyloidosis was similar to lone AS with respect to left ventricular mass and LVEF (57 (45, 64)%). It was similar to lone amyloidosis with respect to lateral S" (0.04 (0.03, 0.06) m/s), NT-proBNP (4149 (1449, 6459) ng/L) and troponin T (56 (34, 100) ng/L). Whilst, prevalence of carpal tunnel syndrome (CTS) (17%) and diastolic function (E/A ratio 1.1 (0.8, 2.8)) were intermediate. Conclusion AS-amyloidosis is not a double insult from AS and amyloidosis, but a mixed phenotype with features similar to lone amyloidosis (cardiac biomarkers), lone AS (remodelling and LVEF) or intermediate (diastology and CTS). Characteristics across all 4 groups Variable Older age controls (n = 81) Lone AS (n = 359) AS-amyloidosis (n = 36) Lone amyloidosis (n = 107) P value Age (years) 82 (80, 84)*†‡ 85 (80, 88)§∞ 88 (85, 92)# 80 (75, 84)

BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p

International audience; Background: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD.Methods and findings: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial.Conclusion: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

Aims: To evaluate the repeatability of cardiac magnetic resonance (CMR) radiomics features on test-retest scanning using a multi-centre multi-vendor dataset with a varied case-mix.Methods and Results: The sample included 54 test-retest studies from the VOLUMES resource (thevolumesresource.com). Images were segmented according to a pre-defined protocol to select three regions of interest (ROI) in end-diastole and end-systole: right ventricle, left ventricle (LV), and LV myocardium. We extracted radiomics shape features from all three ROIs and, additionally, first-order and texture features from the LV myocardium. Overall, 280 features were derived per study. For each feature, we calculated intra-class correlation coefficient (ICC), within-subject coefficient of variation, and mean relative difference. We ranked robustness of features according to mean ICC stratified by feature category, ROI, and cardiac phase, demonstrating a wide range of repeatability. There were features with good and excellent repeatability (ICC ≥ 0.75) within all feature categories and ROIs. A high proportion of first-order and texture features had excellent repeatability (ICC ≥ 0.90), however, these categories also contained features with the poorest repeatability (ICC < 0.50).Conclusion: CMR radiomic features have a wide range of repeatability. This paper is intended as a reference for future researchers to guide selection of the most robust features for clinical CMR radiomics models. Further work in larger and richer datasets is needed to further define the technical performance and clinical utility of CMR radiomics.

PURPOSE The irreversible ErbB family tyrosine kinase inhibitor (TKI) afatinib plus the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to EGFR TKIs. We studied whether the combination of afatinib plus cetuximab compared with afatinib alone would improve progression-free survival (PFS) in patients with treatment-naive EGFR-mutant non–small-cell lung cancer (NSCLC) by preventing or delaying resistance. METHODS Patients with EGFR-mutant NSCLC without prior treatment of advanced disease were enrolled in this phase II, multicenter trial and randomly assigned to receive afatinib 40 mg orally daily plus cetuximab 500 mg/m2 intravenously every 2 weeks or afatinib alone. The primary end point was PFS. RESULTS Between March 25, 2015 and April 23, 2018, 174 patients were randomly assigned, and 168 (83 on afatinib + cetuximab and 85 on afatinib) were eligible. There was no improvement in PFS in patients receiving afatinib plus cetuximab compared with afatinib alone (hazard ratio [HR], 1.01; 95% CI, 0.72 to 1.43; P = .94; median, 11.9 months v 13.4 months). Similarly, there was no difference in response rate (67% v 74%; P = .38) or overall survival (HR, 0.82; 95% CI, 0.50 to 1.36; P = .44). Toxicity was greater with the combination: grade ≥ 3 adverse events related to treatment occurred in 72% of patients receiving afatinib plus cetuximab compared with 40% of those receiving afatinib alone, most commonly rash and diarrhea. Dose reductions were more common in patients receiving the combination, and 30% of patients in this arm discontinued cetuximab due to toxicity. At interim analysis, there was insufficient evidence to support continued accrual, and the trial was closed. CONCLUSIONS The addition of cetuximab to afatinib did not improve outcomes in previously untreated EGFR-mutant NSCLC, despite recognized activity in the acquired resistance setting.

Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P mean 13.6% [6.3–18.8], P mean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P 2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

Introduction: Cardiac involvement determines outcome in systemic amyloidosis, but the relationship between amyloid deposits and outcomes is poorly understood. Many clinical observations are not explained by the simple concept of physical, mechanical replacement of the interstitium by amyloid material. Hypothesis: Preliminary studies in patients with cardiac amyloidosis (CA) support the hypothesis that myocardial ischaemia contributes to cell damage. This study assesses the presence and mechanisms of myocardial ischaemia using CMR with multiparametric mapping and histopathological assessment. Methods: 92 patients with CA (41 AL, 51 ATTR) and 73 without CA (26 with unobstructed coronary arteries; 47 with 3VD) underwent CMR with T1, T2, Extracellular volume (ECV) mapping and adenosine stress with myocardial blood flow (MBF) mapping. 25 cardiac biopsies and 3 explanted hearts with CA were analysed histopathologically. Results: CA patients had severe reductions in stress MBF and myocardial perfusion reserve (MPR)- (1.03ml/g/min±0.50;1.54±0.59 ) compared to patients with unobstructed coronary arteries (2.82 ml/g/min±0.53; 2.94±0.59, p Conclusion: CA is associated with severe myocardial ischaemia demonstrable by histology and CMR perfusion mapping. Histological evaluation indicates a complex pathophysiology, where direct disruption of the vessels by amyloid deposits and reduction in epicardial flow contribute to myocardial ischaemia.

Background: Elderly patients with severe aortic stenosis (AS) are increasingly diagnosed with cardiac amyloidosis (CA). It is unclear whether dual AS-CA has worse outcomes or may even result in futility of transcatheter aortic valve replacement (TAVR). Objective: To identify diagnostic predictors and outcomes of AS-CA compared to lone AS. Methods: Severe AS TAVR referrals at three international sites underwent clinical and laboratory assessment, six-minute walk test, ECG, transthoracic echocardiography with strain analysis, and blinded research 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy, unremarkable serum/urine free light chain assessment; light-chain CA (AL) was diagnosis by endomyocardial biopsy. All-cause mortality was captured from national registries. Results: 408 patients (age 83.4±6.5 years, 49.8% male) were recruited. DPD bone scintigraphy was positive in 11.6% (n=47, Grade-1 3.7%[15]) Grade-2/3 7.9%[32]). Positivity was associated with QRS duration (OR 2.5, 95%CI 1.1-5.5, p=0.02), voltage/mass-ratio (OR 0.4, 95%CI 0.2-0.9, p=0.02), history of carpal tunnel syndrome (OR 1.6, 95%CI 1.1-2.3, p=0.02). An additional two cases had biopsy proven AL-CA. Heart Team decision (blinded to bone scintigraphy) resulted in TAVR in 333 (81.6%), surgical aortic valve replacement in 10 (2.5%) and medical management in 65 (15.9%). After a median of 1.7 years, 22.9% of patients had died. AS-CA had a worse 1-year mortality than lone AS (24.5 vs 13.9%, p=0.045, Figure 1A), but there was no difference post valve intervention (p=0.7), which improved outcomes in both lone AS and AS-CA compared to medical management (Figure 1B+C). Discussion: Dual pathology of AS-CA is common in elderly AS patients. AS-CA is prognostically slightly worse than lone AS, but not if treated by valve intervention. Based on this data, TAVR should not be witheld in AS-CA.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.

BackgroundSARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity.MethodsHealth-care workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n=12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to previously reported pseudovirus neutralising antibody measurements.FindingsA total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r=0.57, pInterpretationMild SARS-CoV-2 infection is associated with heterogenous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. The application of individual assays for diagnostic and epidemiological serology requires validation in time series analysis.FundingCharitable donations via Barts CharityResearch in contextEvidence before this studyWe searched PubMed, medRxiv, and bioRxiv for [“antibody” OR “serology”] AND [“SARS-CoV-2” OR “COVID-19”]. The available literature highlights widespread use of serology to detect recent SARS-CoV-2 infection in individual patients and in population epidemiological surveys. Antibody to virus spike protein S1 domain is widely reported to correlate with neutralising antibody titres. The existing assays have good sensitivity to detect seroconversion within 14 days of incident infection, but the available longitudinal studies have reported variable rates of decline in antibody levels and reversion to undetectable levels in some people over 3 months. High frequency multi-time point serology data for different antibody targets or assays in longitudinal cohorts from the time of incident infection to greater than 3 months follow up are lacking.Added value of this studyWe combine detailed longitudinal serology using the Euroimmun anti-S1 and Roche anti-nucleocapsid protein (NP) assays in 731 health care workers from the time of the first SARS-CoV-2 epidemic peak in London, UK. In 157 seroconverters (using either assay) we show substantial heterogeneity in semiquantitative antibody measurements over time between individuals and between assays. Mathematical modelling of individual participant antibody production and clearance rates in individuals with at least 8 data points over 21 weeks showed anti-S1 antibodies to have a faster clearance rate, earlier transition from the initial antibody production rate to lower rates, and greater reduction in antibody production rate after this transition, compared to anti-NP antibodies as measured by these assays. As a result, Euroimmun anti-S1 measurements peaked earlier and then reduced more rapidly than Roche anti-NP measurements. In this study, these differences led to 21% anti-S1 sero-reversion, compared to 4% anti-NP sero-reversion over 4-5 months.Implications of all of the available evidenceThe rapid decline in anti-S1 antibodies measured by the Euroimmun assay following infection limits its application for diagnostic and epidemiological screening. If generalisable, these data are consistent with the hypothesis that anti-S1 mediated humoral immunity may not be sustained in some people beyond the initial post-infective period. Further work is required to understand the mechanisms behind the heterogeneity in antibody kinetics between individuals to SARS-CoV-2. Our data point to differential mechanisms regulating humoral immunity against these two viral targets.

Background Cardiovascular magnetic resonance (CMR) demonstrates promise in improving patient risk stratification in aortic stenosis (AS). We explored whether machine learning might provide further insights into the prognostic capability of CMR parameters. Methods Severe AS patients (n=440) undergoing AVR were prospectively enrolled across 10 international sites, and CMR performed prior to AVR. A machine learning prediction model using a random survival forest (RSF) was trained with 29 variables, including 13 CMR, 4 echocardiography, and 12 clinical parameters, using post-AVR mortality as an outcome. The impact of the important variables on the outcome (partial dependency) was examined. Results The most predictive CMR parameters in the RSF model were the extracellular volume fraction (ECV%), followed by right ventricular ejection fraction (RVEF), late gadolinium enhancement (LGE%), and indexed left ventricular end-diastolic volume (LVEDVi). Regarding the partial effects, the predicted mortality increased strongly once the ECV% exceeded 26.5% (Figure 1A). The LGE% was associated with an increased risk of mortality, which reached a plateau beyond the level of 2% (Figure 1C). There were U-shaped relationships between mortality and both RVEF and LVEDVi, with the lowest mortality seen at RVEF 70% and LVEDVi 68ml/m2 (Figure 1B, D). These trends of predicted outcomes by each variable were verified in the Kaplan-Meier curves and Cox analyses (Table). In both Cox and RSF models, the predictability was substantially increased when these four CMR parameters were added to conventional clinical risk factors. An AS-CMR risk score comprised of these four parameters presented a stepwise increase in mortality with increasing adverse CMR features (p Conclusions Our machine learning analysis using RSF has identified ECV%, RVEF, LGE%, and LVEDVi as key prognostic markers in severe AS with a nonlinear influence of each parameter on mortality post-AVR. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by grants from the Korean Health Technology R & D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (HI16C0225 and HI15C0399) and the National Institute for Health Research (NIHR) infrastructure at Leeds.

Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None

Background Cardiovascular diseases are an important component of the multi-morbidity syndrome which is associated with negative health outcomes resulting in a major societal economic burden. An objective way to assess multi-morbidity is to calculate a frailty index based on medical deficit accumulation. Late-life frailty has been validated to predict mortality, but little is known about the association between life-course frailty and cardiovascular health in later-life. Purpose To study the association between life-course frailty and later-life heart size and function using data from the world's longest running birth cohort with continuous follow-up. Methods A 45-deficit frailty index (FI) was calculated at 4 age-intervals across the life-course (0 to 16 years old, 19 to 44 years old, 45 to 54 years old and 60 to 64 years old) in participants from the UK 1946 Medical Research Council (MRC) National Survey of Heath and Development (NSHD) birth cohort. The life-course frailty indices (FI0_16, FI19_44, FI45_54 and FI60_64) reflect the cumulative medical deficits at the corresponding age-intervals. They were used to derive FImean and FIsum reflecting overall-life frailty. The step change in deficit accumulation between age-intervals was also calculated (FI2-1, FI3-1, FI4-1, FI3-2, FI4-2, FI4-3). Echocardiographic data at 60–64 years provided: E/e' ratio, ejection fraction (EF), myocardial contraction fraction index (MCFi) and left ventricular mass index (LVmassi). Generalized linear mixed models with gamma distribution and log link assessed the association between FIs and echo parameters after adjustment for sex, socio-economic position and body mass index. Results 1.805 NSHD participants were included (834 male). Accumulation of a single deficit had a significant impact (p13, p Conclusion Frailty during the life-course, overall life-frailty and the step change in deficit accumulation is associated with later-life cardiac dysfunction. Frailty strain appears to have its greatest impact on pathological myocardial hypertrophy (high LVmassi and low MCFi) potentially paving the way to later-life systolic or diastolic dysfunction in susceptible individuals. Funding Acknowledgement Type of funding source: None

Background Cardiac involvement in Fabry Disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with storage reflected by cardiovascular magnetic resonance (CMR) and ECG changes. Objectives We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering. Methods FD patients and age, sex and heart rate matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR (cines, global longitudinal strain [GLS], T1 and T2 mapping, stress perfusion [myocardial blood flow, MBF] and late gadolinium enhancement [LGE]). Results 114 Fabry patients (46±13 years, 61% female) and 76 controls (49±15 years, 50% female) were included. In pre-LVH FD (n=72, 63%), a low T1 (n=32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n=40/72, 56%) also had abnormalities compared to controls: reduced GLS (−18±2 vs −20±2%, P Conclusions FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals. Proposed stages of cardiac involvement Funding Acknowledgement Type of funding source: None

Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4 years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were feasible from 86 patients with median CVF of 14.6% [IQR 7.4–20.3]. Fibrosis was present even in NYHA Class I patients (13.6% [6.3–18.8]), and was significantly higher than the 3.3% [2.6–6.1] obtained from 8 autopsy controls without cardiac disease (P Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although it did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV (27.4±3.3%) correlated with systolic (LVEF Rho=−0.22, P=0.029; LVESVi Rho=0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e' R=0.25, P=0.022), exercise capacity (%VO2max R=−0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Post-operatively, although LVEF remained normal (defined as >50%) in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., Uncoupling of neutralizing antibody and T cell responses to SARS-CoV-2 antigens occurs in some mild or asymptomatic cases of COVID-19.

Studies of adaptive immunity to SARS-CoV-2 include characterisation of lethal, severe and mild cases1-8. Understanding how long immunity lasts in people who have had mild or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed to and infected by SARS-CoV-2 during the early stages of the pandemic are an invaluable resource to study this question9-14. The UK COVIDsortium is a longitudinal, London hospital HCW cohort, followed from the time of UK lockdown9,10 ; weekly PCR, serology and symptom diaries allowed capture of asymptomatic infection around the time of onset, so duration of immunity could be tracked. Here, we conduct a cross-sectional, case-control, sub-study of 136 HCW at 16-18 weeks after UK lockdown, with 76 having had laboratory-confirmed SARS-CoV-2 mild or asymptomatic infection. Neutralising antibodies (nAb) were present in 90% of infected HCW sampled after the first wave; titres, likely to correlate with functional protection, were present in 66% at 16-18 weeks. T cell responses tended to be lower in asymptomatic infected HCW than those reporting case-definition symptoms of COVID-19, while nAb titres were maintained irrespective of symptoms. T cell and antibody responses were discordant. HCW lacking nAb also showed undetectable T cells to Spike protein but had T cells of other specificities. Our findings suggest that the majority of HCW with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multi-specific T cell responses for at least 4 months after mild or asymptomatic SARS-CoV-2 infection.

BackgroundAccess to health services and adequate care is influenced by sex, ethnicity, socio-economic position (SEP) and burden of co-morbidities. However, it is unknown whether the COVID-19 pandemic further deepened these already existing health inequalities.MethodsParticipants were from five longitudinal age-homogenous British cohorts (born in 2001, 1990, 1970, 1958 and 1946). A web and telephone-based survey provided data on cancelled surgical or medical appointments, and the number of care hours received during the UK COVID-19 national lockdown. Using binary or ordered logistic regression, we evaluated whether these outcomes differed by sex, ethnicity, SEP and having a chronic illness. Adjustment was made for study-design, non-response weights, psychological distress, presence of children or adolescents in the household, keyworker status, and whether participants had received a shielding letter. Meta-analyses were performed across the cohorts and meta-regression evaluated the effect of age as a moderator.Findings14891 participants were included. Females (OR 1·40, 95% confidence interval [1·27,1·55]) and those with a chronic illness (OR 1·84 [1·65-2·05]) experienced significantly more cancellations during lockdown (all ppInterpretationThe UK government’s lockdown approach during the COVID-19 pandemic appears to have deepened existing health inequalities, impacting predominantly females, ethnic-minorities and those with chronic illnesses. Public health authorities need to implement urgent policies to ensure equitable access to health and care for all in preparation for a second wave.

AimTo study the association between the life-course accumulation of health deficits and later-life heart size and function using data from the 1946 National Survey of Heath and Development (NSHD) British birth cohort, the world’s longest running birth cohort with continuous follow-up.Methods and ResultsA multidimensional health deficit index (DI) looking at 45-health deficits was serially calculated at 4 time periods of the life-course in NSHD participants (0-16, 19-44, 45-54 and 60 to 64 years), and from these the mean and total DI for the life-course was derived (DImean, DIsum). The step change in deficit accumulation from one time period to another was also calculated. Echocardiographic data at 60-64 years provided: ejection fraction (EF), left ventricular mass indexed to body surface area (LVmassi, BSA), myocardial contraction fraction indexed to BSA (MCFi) and E/e’. Generalized linear models assessed the association between DIs and echocardiographic parameters after adjustment for sex, socio-economic position and body mass index.1,375 NSHD participants were included (46.47% male). For each single new deficit accumulated at any one of the 4 time periods of the life-course, LVmassi increased by 0.91-1.44% (pi decreased by 0.6-1.02% (ppp13.ConclusionThe accumulation of health deficits at any time period of the life-course associates with a maladaptive cardiac phenotype in older age, dominated by myocardial hypertrophy and poorer function. The burden of health deficits appears to strain the myocardium potentially leading to future cardiac dysfunction.

A 55-year-old woman with a recent history of surgically and radioiodine treated thyroid cancer experienced a run of polymorphic ventricular tachycardia with hemodynamic perturbation during anaesthetic induction with propofol, fentanyl and rocuronium for elective surgical excision of right hip metastasis. Electrocardiography showed new T-wave inversion and QT prolongation that subsequently resolved. Cardiac enzymes were elevated but invasive coronary angiography showed unobstructed epicardial coronary arteries. Cardiovascular magnetic resonance showed not only normal biventricular size and systolic function but also a striking pattern of patchy myocardial oedema involving the basal-to-mid anterior, septal and inferior walls and some associated hypertrophy in the anteroseptum (representing focal myocardial swelling from the oedema) but no focal or diffuse myocardial fibrosis. All these abnormalities resolved on subsequent convalescent imaging. A diagnosis of multifactorial acquired long QT syndrome secondary to atypical variant stress-induced cardiomyopathy was made with the likely provoking factors in this case having been the female sex, understandable pre-operative anxiety, anaesthetic drugs, supraglottic airway placement and thyroid dysfunction. An implantable loop recorder during follow-up detected no further significant arrhythmias and she remains well and asymptomatic to date on a low dose of beta-blocker.

This chapter was inadvertently published as an open access chapter. However, the open access for this chapter has now been reverted.

Background Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM), but measurement has variation. Objectives We developed a fully automated machine learning (ML) algorithm for MWT measurement and compared it to international experts using precision (repeatability) on a dataset of HCM patients scanned twice with cardiovascular magnetic resonance (CMR). Methods Training dataset: Endo- and epicardial end-diastolic contours were derived using a fully-automated convolutional neural network trained on 1,923 independent multi-centre multi-disease cases (14 centres from 3 countries, 10 scanner models, 2 field strengths, with balanced pathologies - health, athletes, myocardial infarction, aortic stenosis, HCM, dilated cardiomyopathy, infiltrative diseases) all segmented by a single expert. Patients: 60 HCM patients were scanned twice (scan:rescan) in the same session (no biological variability) at different field strengths and vendors (Siemens, GE, Philips) in 3 centres to allow generalizability. The protocol consisted of long axis cines and a short axis (SAX) bSSFP cine stack. Between scans, patients were brought out of the bore, repositioned on the table and re-isocentered. Wall thickness: MWT was measured in the SAX cine stack in end-diastole (scans A and B) by 11 experts (from 4 continents, 6 countries, 9 centers). For ML performance, the contours were based on a repurposed algorithm used for brain cortical thickness measurement, applying the Laplace equation for all contour points – effectively creating nested smoothly deforming surfaces from endo- to epicardium. We created orthogonal field lines to connect endo-and epicardial points, measured these distances and took the maximum as MWT. Results 1320 MWT measurements by experts were analyzed. Mean MWT varied significantly from 14.9 mm to 19.0 mm (Δ4.1 mm, p Conclusions ML MWT measurement in HCM is superior to all international experts studied with implications for risk stratification and sample sizes for clinical trials.

Background Cardiovascular diseases are an important component of the multimorbidity syndrome which is associated with negative health outcomes resulting in a major societal economic burden. An objective way to assess multimorbidity is to calculate a frailty index based on medical deficit accumulation. Late-life frailty has been validated to predict mortality, but little is known about the association between life-course frailty and cardiovascular health in later-life. Purpose To study the association between life-course frailty and later-life heart size and function using data from the world’s longest running birth cohort with continuous follow-up. Methods A 45-deficit frailty index (FI) was calculated at 4 age-intervals across the life-course (0 to 16, 19 to 44, 45 to 54 and 60 to 64 years) in birth cohort participants of the UK 1946 Medical Research Council National Survey of Heath and Development (NSHD). The 4 resultant frailty indices (FI0_16, FI19_44, FI45_54 and FI60_64) were used to derive FImean and FIsum reflecting overall life frailty. The step change in deficit accumulation between age-intervals was also calculated (FI2-1, FI3-1, FI4-1, FI3-2, FI4-2, FI4-3). Echocardiographic data at 60-64 years provided: left ventricular (LV) ejection fraction (EF), LV mass indexed to body surface area (BSA; LVmassi), BSA-indexed myocardial contraction fraction (MCFi) and LV filling pressure defined as E/e’>13. Generalized linear mixed models (glmm) with gamma distribution and log link or binomial distribution and logit link, assessed the association between FIs and echocardiographic parameters after adjustment for sex, socio-economic position and body mass index. Results 1,805 NSHD participants were included (834 male, mean FI60_64 0.28±0.097, range 0.07-0.70). A unit increase in frailty decreased EF by 11% and 12% for FI45_54 and FI60_64 respectively, by 10% to 12% for FI2-1, FI3-1, FI4-1 and FI4-2, and by 4% and 15% for FIsum and FImean respectively (all p Conclusion Frailty during childhood, young adulthood, middle age and older age associates with having a weaker (↓EF/MCFi), thicker (↑LVmassi) and stiffer (↑E/e’) heart in later-life. The accumulation of new deficits from one age interval to the next also associates with poorer cardiac function in later-life. It appears that multimorbidity and health deficits accumulated over the life-course strain the myocardium resulting in pathological myocardial hypertrophy potentially paving the way to later-life systolic or diastolic dysfunction in susceptible individuals Conflict of Interest None.

Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 6-9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were collected from 86 patients with median CVF of 14.6%[IQR 7.4-20.3]. Fibrosis was present even in NYHA Class I patients (13.6%[6.3-18.8]), and was significantly higher than the 3.3%[2.6-6.1] obtained from 8 autopsy controls without cardiac disease (P Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although CVF did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV correlated with systolic (LVEF Rho=-0.22, P=0.029; LVESVi Rho 0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e’ R=0.25, P=0.022), exercise capacity (%VO2max R=-0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Following surgery, although LVEF remained >50% in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Conflict of Interest None

Background H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. Results We detected chromatin regions with differential acetylation activity (DARs; Padj. < 0.05) between remodeled non-failing patient hearts and healthy donor hearts. The acetylation level of the chromatin region correlated with its RNA polymerase II occupancy level and the mRNA expression level of its adjacent gene per sample. Annotated genes from DARs were enriched in disease-related pathways, including fibrosis and cell metabolism regulation. DARs that change in the same direction have a tendency to cluster together, suggesting the well-reorganized chromatin architecture that facilitates the interactions of regulatory domains in response to myocardial remodeling. We further show the differences between the acetylation level and the mRNA expression level of cell-type-specific markers for cardiomyocytes and 11 non-myocyte cell types. Notably, we identified transcriptome factor (TF) binding motifs that were enriched in DARs and defined TFs that were predicted to bind to these motifs. We further showed 64 genes coding for these TFs that were differentially expressed in remodeled myocardium when compared with controls. Conclusions Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles, we further provide promising TF-encoding genes that could serve as master regulators of myocardial remodeling. Combined, our findings highlight the important role of chromatin regulatory signatures in understanding disease etiology.

Background Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms. Methods and results Two hundred and six healthy volunteers (age range 21–73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, −6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P Conclusion This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals.

The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.MWT analysis was completed by 70 readers (from 6 continents; 91% with5 years' experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range -59% to 117% [SD ±20%] and -61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

Quantification of myocardial perfusion has the potential to improve detection of regional and global flow reduction. Significant effort has been made to automate the workflow, where one essential step is the arterial input function (AIF) extraction. Since failure here invalidates quantification, high accuracy is required. For this purpose, this study presents a robust AIF detection method using the convolutional neural net (CNN) model. CNN models were trained by assembling 25,027 scans (N=12,984 patients) from three hospitals, seven scanners. A test set of 5,721 scans (N=2,805 patients) evaluated model performance. The 2D+T AIF time series was inputted into CNN. Two variations were investigated: a) Two Classes (2CS) for background and foreground (LV mask); b) Three Classes (3CS) for background, foreground LV and RV. Final model was deployed on MR scanners via the Gadgetron InlineAI. Model loading time on MR scanner was ~340ms and applying it took ~180ms. The 3CS model successfully detect LV for 99.98% of all test cases (1 failed out of 5,721 cases). The mean Dice ratio for 3CS was 0.87+/-0.08 with 92.0% of all test cases having Dice ratio >0.75, while the 2CS model gave lower Dice of 0.82+/-0.22 (P0.2). This study proposed, validated, and deployed a robust CNN solution to detect the LV for the extraction of the AIF signal used in fully automated perfusion flow mapping. A very large data cohort was assembled and resulting models were deployed to MR scanners for fully inline AI in clinical hospitals., Accepted by Magnetic Resonance in Medicine on March 30, 2020

Background:Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives:This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods:Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results:Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4to58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p Conclusions:In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% isameasure of left ventricular decompensation and a powerful independent predictor of mortality.

Native myocardial T1 and extracellular volume (ECV) by cardiovascular magnetic resonance imaging are key biomarkers for assessing several heart muscle diseases. Their measurement, however, is influenced by blood T1, either due to myocardial vascular blood volume or via blood pool partial voluming.

The purpose of this study was to validate computed tomography measured ECV (ECVAS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV).Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVA total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVECV

Aims: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. Methods: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. Results: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). Conclusion: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.