AIMS:To determine the prevalence of asymmetric septal hypertrophy(ASH) across health and in diseases associated with left ventricular hypertrophy(LVH), including hypertrophic cardiomyopathy(HCM). METHODS AND RESULTS:We analysed two complementary datasets. First, a large UK Biobank healthy reference cohort(n = 4,020) was used to model demographic determinants of septal-to-lateral wall thickness ratio(SLR) and to provide the reference group for age-, sex-, and body-surface area-adjusted comparisons. Second, a multi-cohort clinical CMR dataset included 1,655 subjects comprising local healthy volunteers, athletes, patients with hypertension, aortic stenosis, Fabry disease, AL amyloidosis, ATTR amyloidosis, and HCM. LVH was defined by maximum wall thickness(MWT) ≥ 15 mm and asymmetry defined as SLR≥1.3. Left ventricular morphology was classified as normal, asymmetric remodelling(SLR≥1.3;MWT<15 mm), symmetric hypertrophy(SLR<1.3;MWT≥15 mm) or ASH(SLR≥1.3;MWT≥15 mm). ASH was highly prevalent in HCM(61%) but was also observed in ATTR amyloidosis(37%), AS(26%), and AL amyloidosis(23%). In the healthy reference cohort, a higher septal-to-lateral ratio was independently associated with older age, female sex, and larger BSA(p < 0.001). After adjustment for these demographic factors, only HCM retained a clinically meaningful excess in septal asymmetry(ΔSLR=+0.27;p < 0.001). In contrast, the apparent asymmetry in non-HCM cohorts was partly explained by demographic variation. After adjustment, only HCM showed a clinically meaningful excess in SLR, whereas other disease cohorts showed either no material difference or small negative differences relative to healthy controls. CONCLUSION:ASH is a common but non-specific finding in diseases associated with LVH. Septal asymmetry increases with age and body-size and is more pronounced in women. After adjusting for age, sex, and body-size, disproportionate septal asymmetry was most characteristic of HCM.

BACKGROUND:Incidental findings are often found in imaging research, especially in older people (aged ≥75 years). Understanding their prevalence is essential to inform consent and disclosure protocols as well as anticipate onward investigation balanced against minimising unnecessary anxiety and health-care burden. The aim of this study was to determine the prevalence of incidental findings in a population-based sample of individuals aged 75-77 years using cardiovascular magnetic resonance (CMR) imaging and to inform duty-of-care frameworks for their reporting. METHODS:MyoFit46 was a prospective imaging cohort substudy of the National Survey of Health and Development (NSHD) study. Participants were prospectively recruited from the NSHD study, between May 18, 2020, and March 15, 2024, and underwent 3-Tesla contrast-enhanced CMR. An incidental finding was defined as a previously unknown abnormality that had not been identified by the participant or the research team before the study date. Incidental findings were classified into cardiac, non-cardiac, and clinical, and predefined according to the required urgency of follow-up as routine (reported to participants and their general practitioners within 28 days) or or immediate (reported within 48 hours). This study is registered with ClinicalTrials.gov, NCT05455125. FINDINGS:Of 505 participants prospectively recruited, 484 (96%) completed a full CMR scan. Of these, 432 (89%) had at least one incidental finding, including 58 (12%) immediate and 429 (89%) routine findings. Incidental findings were more common in male participants than in female participants (routine: 250 [92%] of 271 men vs 182 [85%] of 213 women, p=0·018; immediate: 39 [14%] of 271 men vs 19 [9%] of 213 women, p=0·069). The commonest routine cardiac incidental finding was late gadolinium enhancement (145 [43%] of 334 participants) and the commonest immediate cardiac finding was a left ventricular ejection fraction lower than 40% (seven [2%] of 334 participants). Non-cardiac incidental findings were predominantly routine (203 [42%] of 484) whereas immediate non-cardiac incidental findings were very uncommon (four [1%] of 484). Clinical findings were found in 201 (42%) of 484 participants, of which 28 (6%) were classified as immediate and 187 (39%) classified as routine. INTERPRETATION:CMR and baseline assessments revealed that incidental findings are common in imaging research in adults aged 75 years and older, underscoring the need for robust duty-of-care frameworks to ensure timely, ethical, and appropriate management of these findings in older age. These findings provide a population benchmark that can inform the design, governance, and resource planning of future large-scale imaging studies in ageing cohorts. FUNDING:British Heart Foundation and Medical Research Council.

Background Patients with angina and no obstructive coronary artery disease (ANOCA) frequently receive empirical antianginal therapy that fails to target underlying pathophysiological mechanisms. Whether stress perfusion cardiac magnetic resonance (CMR)-guided endotyping and stratified medical therapy improves treatment satisfaction and appropriate medication prescribing in this population is uncertain. Methods In the Coronary Microvascular Angina CMR Imaging Trial, 250 patients with suspected ANOCA, who had undergone invasive coronary angiography demonstrating no obstructive disease, were enrolled and underwent stress perfusion CMR with quantification of myocardial blood flow. Participants were randomised 1:1 to CMR-guided management (intervention) or angiography-guided management (control). Treatment satisfaction was assessed using the validated Treatment Satisfaction Questionnaire for Medication (TSQM-9) at baseline, 6 months and 12 months. Medication prescriptions were documented at these time points. Results Stress CMR imaging led to diagnostic reclassification in 53.0% of patients, with microvascular angina diagnosed in 51.0%. At 12 months, global treatment satisfaction was significantly higher in the intervention group compared with controls (adjusted difference, 19.30 units (95% CI 13.89 to 24.71); p<0.001), with consistent improvements across the effectiveness and convenience domains. CMR-guided management was associated with more appropriate prescribing, including higher use of preventive therapies (85.5% vs 67.5%; p=0.001), and more targeted antianginal prescribing, including calcium channel blockers (43.5% vs 27.0%; p=0.008) and long-acting nitrates (56.5% vs 32.5%; p<0.001). Conclusions In patients with ANOCA, non-invasive CMR-guided endotyping substantially improves treatment satisfaction and enables more appropriate, mechanism-targeted pharmacotherapy compared with angiography-guided care. Trial registration number ClinicalTrials.gov ID NCT04805814 .

Pretrained segmentation models for cardiac magnetic resonance imaging (MRI) often fail to generalize across imaging sequences due to substantial contrast variations. These variations arise from different imaging protocols, yet fundamentally, all contrasts are governed by the same underlying tissue properties, primarily captured by three components: the magnetization strength (M0), T1, and T2. Building on this insight, we introduce Reverse Imaging, a physics-driven framework for data augmentation and domain generalization in cardiac MRI. Our method infers tissue properties from observed MR images with annotation by solving an ill-posed nonlinear inverse problem, regularized by a generative prior. The prior is learned from the multiparametric saturation-recovery single shot acquisition (mSASHA) dataset for joint cardiac T1 and T2 mapping. In inference, we characterize imaging sequences as weak, moderate, or strong observations according to the physical information they provide and the degree of ill-posedness. This motivates an iterative prior-learning strategy that uses moderate T1-mapping observations to alleviate mSASHA data scarcity via pseudo tissue-property estimates. We further integrate MRI physics into posterior inference by expressing the sequence model as a likelihood term guiding the reverse diffusion process. For widely used but weak cine observations, we develop a sequence-specific ControlNet to improve efficiency and spatial consistency. Extensive experiments on eight unseen cardiac MRI sequences with markedly different contrast mechanisms show that Reverse Imaging yields plausible tissue-property estimates, supports synthesis of diverse yet physically consistent contrasts, and improves segmentation robustness under severe cross-sequence shifts.

Aims In individuals with type 2 diabetes mellitus (T2DM), both myocardial ischemia and myocardial infarction (MI) are associated with adverse cardiovascular outcomes. The incremental prognosis of both risks is unknown. We aimed to investigate whether abnormal myocardial perfusion reserve (MPR), as a surrogate marker for ischemia and presence of MI offers incremental prognostic value in predicting major adverse cardiovascular and cerebrovascular events (MACCE) in patients with T2DM. Methods and results A retrospective multicentre cohort of 572 individuals with T2DM and healthy controls underwent quantitative stress myocardial perfusion cardiovascular magnetic resonance (CMR) to determine MPR and late gadolinium enhancement (LGE) to identify MI. Patients were divided into three groups: MI- and normal MPR, MI+ or abnormal MPR and MI+ and abnormal MPR. Cox proportional hazard models quantified associations between MPR and MI with MACCE (composite of all-cause death, MI, stroke, heart failure hospitalization, and late coronary revascularization>90 days after the CMR scan). Over a median of 28 months (IQR 25-31 months), 81 participants (14%) accrued at least one MACCE, including 25 (4%) deaths. Presence of either abnormal MPR or MI was associated with increased MACCE (MI- and normal MPR: 8% MACCE; MI+ or abnormal MPR: 15% MACCE (adjusted HR compared with normal 1.86 (95% CI 1.06-3.25, P = 0.03)); presence of both MI and abnormal MPR had the highest event rate: 30% MACCE (adjusted HR compared with normal 3.24 (95% CI 1.75-6.01, P < 0.001)). Conclusion In T2DM, abnormal MPR or MI are associated with MACCE, and the presence of both offers incremental prognostic value.

Background Electrocardiographic (ECG) devices in magnetic resonance (MR) scanners have a narrow bandwidth and suffer from signal distortion, preventing measurement of QRS/ QT durations, or detection of ST/ T-wave changes during ischaemia. We integrated an external device with novel post-processing software into a 3 Tesla (T) scanner to assess feasibility and accuracy for reconstructing 12-lead ECGs prior to and during adenosine infusion. Methods Reference 12-lead ECGs were first recorded outside the MR-environment. Using three MR-safe electrode patches, in-bore ECGs were then recorded prior to and during adenosine infusion. Post-processing removed artefacts and 12-lead ECGs were reconstructed from the raw signal using a subject-specific matrix. In-bore and reference ECGs were compared using Pearson’s correlation coefficient on the PQRST waveform and by manual measurements of QRS and QT durations. Adenosine-induced ischaemic changes were compared with corresponding territories on stress perfusion maps. Results In 26 participants (70.8 ± 13.0 years; 34.6

BACKGROUND:Alterations in myocardial perfusion and fibrosis are key components in the pathophysiology of heart failure (HF). However, the incremental prognostic value of combining myocardial perfusion and fibrosis remains unclear. The purpose of this study was to evaluate the incremental prognostic value of myocardial perfusion and diffuse fibrosis as defined by cardiovascular magnetic resonance (CMR) in patients with HF. MATERIALS AND METHODS:We collected data from prospectively recruited patients who were clinically diagnosed with HF and referred for CMR assessment between November 2017 to April 2024. Stress/rest myocardial blood flow (MBF) and perfusion reserve (MPR) were calculated from QP-CMR. Extracellular volume fraction (ECV) was calculated using T1 mapping. The primary endpoint was defined as a composite of HF hospitalization (HFH) and all-cause mortality, based on the timing of the first event. Univariate and multivariate Cox regression analysis, and global chi-square analysis were used to assess prognostic performance. RESULTS:A total of 677 patients with HF (median (interquartile range) 63.2 (55.2-72.3) years; 436 male.) were enrolled. During a median 3.5 year follow-up, 109 patients (16.1%) reached the primary endpoints (59 deaths and 50 HFHs). Lower tertile of MPR [adjusted hazard ratio (aHR) 1.74 (95% confidence interval 1.18-2.56), p=0.005) and higher tertiles of native T1 [aHR 1.74 (1.16-2.59), p=0.007] and ECV [aHR 2.35 (1.58-3.49), p<0.001] were associated with the occurrence of the primary endpoint, whereas stress and rest MBF were not significantly associated. Patients exhibiting both high-risk MPR and high-risk ECV had the poorest prognosis [aHR 4.01 (2.28-7.03), p<0.001] whereas patients with only isolated high-risk MPR (aHR 1.74 (1.06-2.86), p=0.027), or high-risk ECV [aHR 2.36(1.36-4.09), p=0.002] demonstrated significantly worse prognoses than patients with both parameters within the low-risk range. Adding ECV to age, sex, and conventional parameters increased the global chi-square values from 33.79 to 50.34 (p<0.001), and further addition of MPR to 57.78 (p=0.006). CONCLUSIONS:QP-CMR and T1 mapping provide incremental, complementary prognostic information for predicting adverse outcomes in HF patients. Impaired myocardial perfusion may be an important marker for risk stratification in addition to myocardial fibrosis in HF patients.

AIMS:Heart transplant (HTx) patients are known to be at risk of coronary microvascular dysfunction as well as having decreased exercise capacity. The aim of this study was to investigate if microvascular function in HTx patients differs from healthy controls and is related to objective measures of exercise capacity. METHODS AND RESULTS:Twenty-nine HTx patients (51 ± 15 years, 34% women) and 26 healthy controls (57 ± 10 years, 38% women) underwent CMR. Quantitative myocardial perfusion maps were acquired using single-bolus (0.05 mmol/kg), dual-sequence perfusion mapping at adenosine stress and at rest. In addition, all HTx patients performed a maximal cardiopulmonary exercise test with gas-exchange analysis for objective assessment of exercise capacity. Heart transplant patients had lower stress myocardial perfusion (2.9 ± 0.8 vs 3.4 ± 0.8, p = 0.03) and lower myocardial perfusion reserve (MPR) (2.7 ± 0.7 vs 3.8 ± 1.2, p < 0.001) compared to healthy controls. Furthermore, MPR in HTx patients was correlated with maximal workload (R2 = 0.25, p = 0.016), O2 pulse (R2 = 0.21, p = 0.026), peak O2 consumption (VO2 peak) (R2 = 0.25, p = 0.015) and O2 consumption (VO2) at the anaerobic threshold (AT) (R2 = 0.27, p = 0.011). CONCLUSION:Microvascular function as assessed by quantitative CMR perfusion mapping is lower in HTx patients than in healthy controls and is partly related to objective measures of exercise capacity.

Aims:In patients with heart failure with reduced ejection fraction (HFrEF), determining the aetiology of cardiac dysfunction has important therapeutic and prognostic implications. Cardiovascular magnetic resonance (CMR) enables comprehensive phenotyping of HFrEF; however, it remains uncertain whether the choice of pharmacological stress agent influences the hyperaemic response required for reliable ischaemia assessment. We sought to compare the hyperaemic effects of adenosine and dobutamine in patients with HFrEF using quantitative perfusion CMR. Methods and results:Patients with HFrEF [left ventricular ejection fraction (LVEF) ≤40%] prospectively underwent 3-Tesla CMR comprising functional cine imaging, late gadolinium enhancement (LGE), and first-pass perfusion imaging at rest and during pharmacological stress with (i) adenosine (140-210 μg/kg/min) and (ii) dobutamine (10-30 µg/kg/min). Perfusion maps were reconstructed inline with automated, pixel-wise quantification of myocardial blood flow (MBF). The hyperaemic response, defined by global myocardial perfusion reserve (MPR), was calculated as the quotient of stress and rest MBF and compared between stress protocols. Fifty-three patients with HFrEF (mean age 63 ± 10 years, 77% male, mean LVEF 36 ± 10%, infarction 59%, and non-ischaemic focal fibrosis 21%) with paired adenosine and dobutamine stress-perfusion data were analysed. Compared with dobutamine, adenosine produced a higher global MPR [mean difference: +0.61 (95% CI: 0.35, 0.88); P < 0.001], which remained significant at the segmental level following adjustment for age, sex, type 2 diabetes, LVEF, and LGE presence [mean difference: +0.63 (95% CI: 0.55, 0.71); P < 0.001]. Conclusion:In patients with HFrEF, adenosine induces a greater hyperaemic response than dobutamine; however, whether this impacts on the diagnostic assessment of ischaemia remains to be established (Trial registration: NCT03661827).

AIMS:Assessing cardiac function is critical for managing cardiovascular disease, guiding treatment, monitoring progression, and risk stratification. While left ventricular (LV) ejection fraction (LVEF) is firmly established, it has limitations. Myocardial contraction fraction (MCF)-the ratio of stroke volume to myocardial volume, is simple to compute without additional analysis and offers a promising alternative to LVEF. METHODS AND RESULTS:MCF was assessed across four datasets spanning healthy controls and chronic structural cardiac disease, with direct comparison to LVEF. Association between age, sex, and MCF were investigated in 3541 healthy subjects from the UK Biobank and sex-specific reference ranges derived. Several cohorts were recruited to investigate the discriminative power of MCF and LVEF between health and physiological adaption (n = 278 veteran athletes), pathological hypertrophy [hypertrophic cardiomyopathy, amyloid, Fabry, severe aortic stenosis (AS), and hypertension (HTN); n = 633], and dilatation [n = 103 dilated cardiomyopathy (DCM)]. Ability to track disease severity was assessed by looking at 41 558 subjects from the UK Biobank. Finally, prognostication was assessed on 1277 consecutive patients from an independent external dataset. All images were analysed using the same validated artificial intelligence algorithm. MCF varied with sex (mean MCF: 0.94 male; 1.1 female) but not age. Sex-specific reference ranges were established: [0.68-1.20] for male and [0.82-1.38] for female. MCF decreased in pathological disease (e.g. mean MCF: 0.72 HCM; 0.69 severe AS; 0.5 amyloid; 0.9 HTN) but there was no significant decrease in LVEF other than in amyloid (mean EF: 76% HCM; 64% severe AS; amyloid 56%; 65% HTN). Both MCF and ejection fraction (EF) decreased in DCM (EF 34%; MCF 0.58). MCF decreased with worsening HTN, whereas LVEF increased (P < 0.05). MCF had superior prognostic ability to LVEF (MCF vs. LVEF: HR = 0.772 vs. HR = 0.816; χ2 = 198 vs. χ2 = 151; P < 0.001). CONCLUSION:We established MCF reference ranges, showing superior performance for detecting early disease and tracking progression compared with LVEF. MCF offers enhanced prognostic utility, complementing established metrics of LV function.

Most high-field MRI scanners conduct imaging using phased-array coils, in which the signals received by an array of coil elements are combined for downstream processing. Optimally combining these signals requires knowledge of each coil's spatial sensitivity profile, which can be acquired from a volume coil with homogeneous sensitivity across the field-of-view. However, this approach is not often used on high-field MRI scanners, especially on non-clinical systems; therefore, this work uses an algorithm based on the singular-value decomposition (SVD), called SVD-B1, to estimate coil sensitivities directly from the array data itself. Images produced by SVD-B1 are devoid of wormhole artifacts and open-ended fringe lines commonly seen in more conventional reconstructions. Quantitative Susceptibility Maps (QSMs) produced using the algorithm were compared to those produced using other combination algorithms across clinically relevant regions of in-vivo and postmortem human brains. As progressive levels of simulated noise were added to the data, SVD-B1's QSMs were up to 3% (in-vivo) and 13% (postmortem) more consistent (as measured by their Intraclass Correlation Coefficient) than those from other algorithms. Additionally, these QSMs were up to 8.5% (in-vivo) and 36% (postmortem) more accurate than other QSMs with respect to a "single-coil" reference. A parallel imaging extension of SVD-B1, called SVD-B1 GRAPPA, achieved similar results for QSMs generated from progressively more accelerated acquisition data. These results show that SVD-B1 can improve the sensitivity of high-resolution QSM to subtle changes in fine-grained tissue structures (e.g., in neurodegenerative disease) and help reduce scan times in clinical settings where shorter scans are imperative.

Importance:Patients undergoing aortic valve replacement (AVR) for chronic severe aortic regurgitation (AR) based on current guideline-based thresholds may have irreversible myocardial scarring. Objective:To quantify reverse remodeling, functional recovery, and symptomatic change after AVR and assess whether myocardial fibrosis is associated with incomplete recovery. Design, Setting, and Participants:In this prospective longitudinal observational study, patients with chronic severe AR referred for AVR by a cardiology team were included. Key exclusion criteria were previous valve surgery, moderate or greater valve disease, and other primary cardiomyopathies. Included patients underwent paired biomarkers, echocardiography, cardiopulmonary exercise testing, and cardiovascular magnetic resonance (CMR) at baseline and at a median of 7 months after AVR. The study took place at 2 tertiary cardiothoracic centers in London, United Kingdom, with enrollment from August 2021 to October 2023. Data were analyzed from January to April 2026. Exposure:AVR. Main Outcomes and Measures:Left ventricular (LV) reverse remodeling (change in LV end-diastolic volume [LVEDV] and LV mass) post-AVR and preoperative correlates of incomplete recovery, with prespecified focus on CMR fibrosis markers (late gadolinium enhancement [LGE] and extracellular volume [ECV]). Results:Seventy-two patients (median [IQR] age, 60 [6-70] years; 59 [82%] male, 35 [49%] with bicuspid aortic valve) completed paired studies. Median (IQR) regurgitant volume fell from 61 (38-83) mL to 5 (3-8) mL; median (IQR) LVEDV fell 44% from 273 (211-307) mL to 153 (130-177) mL; and median (IQR) LV mass fell 21% from 200 (159-226) g to 158 (137-184) g (all P < .001). Indexed intracellular volume declined 21% and indexed extracellular volume 15% (26 mL/m2 to 22 mL/m2; P < .001), raising extracellular volume fraction (ECV%) from 27.4% to 29.1% (P < .001). LGE as a percentage of LV mass was unchanged (2.3% to 2.4%; P = .36); baseline LGE burden was associated with less regression of LV mass (χ22 = 29.4; P < .001) and LVEDV at 7 months (χ21 = 7.9; P = .007). New York Heart Association class and quality of life improved (median [IQR] EQ-5D index improved from 0.89 [0.78-1.00] to 0.94 [0.81-1.00]; P < .001), but maximum oxygen consumption was unchanged (22.6 mL/kg/min to 21 mL/kg/min; P = .08). N-terminal pro-B-type natriuretic peptide decreased slightly (228 pg/mL to 198 pg/mL; P = .27), with a larger fall in patients with evidence of decompensation (n = 31; 469 pg/mL to 279 pg/mL; P = .02). Conclusions and Relevance:In this study, AVR was associated with substantial reverse remodeling at 7 months, including regression of hypertrophy and a fall in indexed extracellular (matrix) volume; the extracellular volume fraction rose, as cellular regression outpaced matrix regression. Focal scar, as a proportion of myocardium, was unchanged. Preoperative focal scar was independently associated with less recovery and may mark incomplete remodeling. Objective functional recovery did not improve at this time point.