Background: Iron deposition following intramyocardial hemorrhage in ST elevation myocardial infarction (STEMI) has a mechanistic role in adverse left ventricular remodeling. Current cardiovascular magnetic resonance imaging-based methods for measuring myocardial iron in STEMI, including T2*, T1, and T2 mapping, are limited. Iron-mediated T1, T2, and T2* relaxation time shortening is opposed by edema-mediated prolongation of relaxation times, hindering the accuracy of these techniques. In contrast, quantitative susceptibility mapping (QSM) measures intrinsic tissue magnetic susceptibility, potentially resulting in higher specificity for iron detection in the setting of infarct-related myocardial edema. The objective of this work is to characterize the performance of QSM for the detection of hemorrhagic iron in the context of STEMI. Methods: 22 patients with STEMI were scanned using QSM and T2* mapping sequences. Presence/absence of iron, image quality, and diagnostic confidence were assessed by two expert readers for QSM, T2* mapping, and T2* weighted imaging (longest echo-time T2* map source image). The volume of intramyocardial hemorrhage was quantified for each technique and compared to the volume of microvascular obstruction determined by lategadolinium enhancement imaging. Mass of hemorrhagic iron in each case was determined using QSM and T2* maps. Results: In the qualitative analysis, QSM had significantly improved diagnostic confidence and image quality compared to both T2* maps and T2* weighted images. For quantitative analysis, the volume of intramyocardial hemorrhage determined by QSM had a significantly stronger correlation vs the reference standard than both T2* map and T2* weighted imaging. There was a strong correlation between the mass of hemorrhagic iron calculated by T2* map and QSM. Conclusion: This work demonstrates, in a patient population, the opportunity QSM presents for improving the assessment of hemorrhagic iron in the context of STEMI. Full evaluation in a large clinical trial is now warranted.

AIMS:The impact of particulate matter (PM) exposure on early myocardial remodelling remains incompletely understood. Cardiac magnetic resonance (CMR) mapping provides sensitive markers of diffuse myocardial fibrosis and inflammation that may reveal subclinical injury. METHODS AND RESULTS:Patients with structurally normal hearts and no late-gadolinium-enhancement on CMR from May 2020 to November 2024 were included. Long-term exposure to PM2.5 and PM10 was derived from the nearest European-Environment-Agency monitoring stations. Associations between PM and CMR parameters were tested with multivariable linear and logistic regression adjusted for demographic, clinical, socioeconomic factors, and inflammatory markers. Two-hundred-thirty-one patients (45 ± 21 years; 53% males; mean annual PM2.5 and PM10 exposure of 28.6 ± 14.8 µg/m3 and 56.0 ± 35.3 µg/m3) were included. After adjustment, exposure to PM2.5 (β & 0.034%; 95% CI 0.005-0.063; P & 0.023) and PM10 (β & 0.021 per 1 µg/m3; 95% CI 0.009-0.032; P & 0.001) were associated with higher synthetic-extracellular volume (ECV), whereas only PM2.5 was associated with higher native T1 (β & 0.317 ms per 1 µg/m3; 95% CI 0.07-0.564; P & 0.012). No associations were observed with other CMR parameters, including T2 mapping. By multivariable logistic regression, PM2.5, but not PM10, was associated with increased native T1 and synthetic-ECV. The association between PM and mapping was most pronounced in males and patients ≥50 years, and no mediation effect of inflammatory markers was found. CONCLUSION:In individuals with structurally normal hearts, chronic exposure to PM2.5 and PM10 was associated with higher synthetic-ECV values, suggesting early diffuse myocardial fibrosis related to air pollution.

BACKGROUND:Mitral valve prolapse (MVP) reflects a connective tissue abnormality of the mitral leaflets, but systemic manifestations beyond the valve in nonsyndromic MVP remain uncertain. Cardiovascular magnetic resonance (CMR) allows a comprehensive assessment of cardiac chambers, aortic dimensions, and skeletal indexes. We investigated systemic morphofunctional features suggestive of connective tissue alterations in nonsyndromic MVP. METHODS:In this single-centre, retrospective case-control study, 120 patients with MVP without more than mild mitral or aortic regurgitation, bicuspid aortic valve, hypertension, competitive sport, or known or suspected syndromic connective tissue disease were matched 2:1 for age, sex, body surface area (BSA), and body mass index with 60 control subjects undergoing CMR. RESULTS:Compared with control subjects, subjects with MVP showed greater aortic annulus (12.9 ± 1.8 mm/m2 vs 12.1 ± 1.3 mm/m2; P = 0.003), aortic root (18.5 [interquartile range (IQR) 17.1-20.3] vs 17.3 [IQR 15.8-18.7] mm/m2; P < 0.001), Haller index (2.7 [IQR 2.4-3.0] vs 2.6 [IQR 2.4-2.8]; P = 0.021), and kyphosis angle (37.0 [IQR 29.0-40.0] vs 27.5 [IQR 22.0-31.5]; P < 0.001). Subjects with MVP also exhibited higher extracellular volume, T2-mapping values, left ventricular end-diastolic and end-systolic volumes and mass, and left atrial volume. After controlling for sex, age, and BSA, MVP remained associated with the dimensions of the aortic annulus (β = 1.34; P = 0.001), aortic root (β = 1.93; P = 0.001), Haller index (β = 0.21; P = 0.008), and kyphosis angle (β = 8.46; P < 0.001). No excess of other connective tissue disorder features was observed compared with control subjects. CONCLUSIONS:In this patient cohort, nonsyndromic MVP was associated with subtle but significant morphofunctional changes in the cardiac chambers, proximal aorta, and thoracic skeleton. Whether these findings potentially reflect underlying connective tissue disorders, warrants further longitudinal studies on their genetic background and clinical implications.

INTRODUCTION:The left atrioventricular coupling index (LACI) has emerged as a potential prognostic marker in several clinical settings. This study evaluated the prognostic value of cardiac magnetic resonance (CMR)-derived LACI in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). METHODS:Patients from the multicentre DERIVATE registry with LVEF <50% who underwent CMR were included. LACI was calculated as the ratio between left atrial and left ventricular end-diastolic volumes. Univariable and multivariable Cox regression models estimated hazard ratios (HR) with 95% confidence intervals (CI) for predicting all-cause mortality (ACM), ACM or HF, and HF alone (competing-risk analysis). Time-dependent receiver operating characteristic analysis identified optimal cut-offs for 3-year outcomes. RESULTS:A total of 2170 patients were included (mean age 59.8 ± 13.9 years; 24.7% women; mean LVEF 31.6 ± 11.3%). Median follow-up was 1016 days (580-1609). Median LACI was 19.4% (13.3-28.8). During follow-up, ACM occurred in 191 patients (8.8%), ACM or HF in 565 (26.0%), and HF in 442 (20.4%). After adjustment for clinical and CMR parameters, including LVEF and late gadolinium enhancement (LGE), each 5% increase in LACI was associated with higher risk of ACM (HR 1.06, 95% CI 1.01-1.11; P = .016), ACM or HF (HR 1.09, 95% CI 1.06-1.12; P < .001), and HF (HR 1.09, 95% CI 1.05-1.12; P < .001). The optimal cut-off for ACM was LACI ≥21% (AUC 0.617, 95% CI 0.561-0.673), identifying patients at higher risk of ACM, ACM or HF, and HF (log-rank P < .001 for all). CONCLUSION:CMR-derived LACI independently predicts ACM and HF in patients with reduced LVEF and provides incremental prognostic value beyond LVEF and LGE. A cut-off of ≥21% identifies higher-risk patients and may support clinical risk stratification.

Abstract Background Primary hypertension is increasingly prevalent in adolescents and young adults, but the underlying circulatory changes in this age group are poorly understood. We examined the haemodynamic aetiology of hypertension in untreated young people using cardiac magnetic resonance imaging. Methods Participants aged 10–30 years were prospectively recruited into an observational cross-sectional study. Hypertensive untreated participants were recruited from paediatric and adult hypertension clinics and compared with normotensive controls. Hypertension was defined using standard clinical guidelines. Cardiac magnetic resonance imaging was used to determine cardiac geometry and aortic dimensions using a 1.5 Tesla Siemens Scanner. Key haemodynamic variables were derived from left ventricular volumes acquired during a short-axis stack sequence and from post processing analysis. Blood pressure was measured at the time of cardiac magnetic resonance imaging using a validated oscillometric blood pressure monitor. Findings Results from 92 participants are presented, 41 normotensive and 51 hypertensive, similar in age and sex with higher body mass index in the hypertensive compared to normotensive group (Table 1). Mean (±SD) cardiac output was higher in hypertensive versus normotensive groups (7.8 ± 1.8 versus 6.2 ± 1.7 L/min; P < 0.001), driven by higher heart rate rather than by higher stroke volume. There were no differences in systemic vascular resistance or proximal aortic pulse wave velocity. Conclusion These results suggest that in overweight/obese adolescents and young adults, higher cardiac output is a key determinant of hypertension. They implicate derangement of the autonomic nervous system rather than vascular remodelling as the earliest mechanism underlying hypertension in this age group.

AIMS:Current models predicting cardiovascular biological age rely on radiomics or complex large feature sets including T1 and strain. We developed and validated a machine learning-based cardiovascular biological age estimate (HeartAge) using cardiovascular-magnetic-resonance (CMR) phenotypes and assessed the prognostic value of its deviation from chronological age (HeartAge-gap) for cardiovascular outcomes and mortality. METHODS AND RESULTS:HeartAge was developed using gradient-boosting regression in 3760 healthy UK-Biobank participants based on readily extractable CMR phenotypes. HeartAge-gap was defined as the difference between HeartAge and chronological age. The association of HeartAge-gap with prevalent cardiovascular conditions and composite cardiovascular outcome or all-cause mortality was tested in 31 784 UK-Biobank participants (64 ± 7 years; 16 640 females) and validated in 897 Multi-Ethnic Study of Atherosclerosis (MESA) participants (60 ± 10 years; 472 females) using logistic and Cox regression, respectively. Over a median 5.5-year follow-up (IQR: 4.7-7.1), 2316 (7.3%) and 363 (1.1%) participants experienced the composite cardiovascular outcome and all-cause mortality, respectively. Each one-year increase in HeartAge-gap, was associated with the composite cardiovascular outcome in females (HR: 1.022, 95% CI: 1.001-1.044, P = 0.048) and males (HR: 1.017, 95% CI: 1.002-1.033, P = 0.027) independently of chronological age and confounders including, body-mass-index, ischaemic heart disease, diabetes, and hypertension. In females only, increased HeartAge-gap predicted all-cause mortality (HR: 1.061, 95% CI: 1.007-1.118, P = 0.027), regardless of chronological age. In female MESA participants only, increased HeartAge-gap predicted the cardiovascular outcome (HR: 1.113, 95% CI: 1.025-1.210, P = 0.011) independently of chronological age and other confounders. CONCLUSION:A biologically older cardiovascular system was independently associated with adverse cardiovascular outcomes across both sexes. In females, advanced cardiovascular ageing also predicts all-cause mortality, irrespective of chronological age.

AIMS:Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy of sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). The aim of current analysis is to evaluate the prognostic impact of late gadolinium enhancement-papillary muscles (LGE-PMs) at cardiovascular magnetic resonance (CMR) and specifically its capability to re-stratify the arrhythmic risk on top to the DERIVATE-ICM Risk Score previously published. METHODS:Eighty-hundred-thirty-nine patients (mean age 65 ± 11 years; males:721[86%]) with ICM and TTE-LVEF <50% were enrolled from the DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy- Ischemic Cardiomyopathy). Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS:During a median follow-up of 1054 days, MAACE occurred in 86 (9.7%). DERIVATE-ICM Risk Score quartiles Q2-Q3 (HR:2.124 [95% CI:1.084-4.162]; p = 0.028), Q4 (HR: 3.865 [95% CI: 1.875-7.970]; p < 0.001) and the involvement of isolated posteromedial (P)PM (HR:1.985 [95% CI:1.073-3.673]; p = 0.029) were independent predictors of MAACE. The Kaplan-Meier survival curves showed a higher event-free rate in absence of LGE-PPM in patients categorized in the DERIVATE-ICM Risk Score quartiles Q2-Q3 (p = 0.018). Finally, adding LGE-PPM involvement on top of the model included TTE LVEF<35% plus DERIVATE-ICM Risk Score quartiles Q2-Q3 provided a significant improvement of prognostic stratification (p = 0.044). CONCLUSION:This study suggests that, in a wide population of ICM patients, LGE-PPM is independently associated with the occurrence of MAACE. In the intermediate quartiles of the DERIVATE-ICM Risk Score, the absence of LGE-PPM, when added to the Score, may contribute to downward re-stratification of arrhythmic risk. CLINICAL TRIAL REGISTRATION:RCT#NCT03352648.

Tricuspid regurgitation (TR) has a community prevalence of 3%, which increases with age and affects up to 7% of elderly patients. TR is secondary (functional) in 90% of cases (usually resulting from left heart disease and/or pulmonary hypertension), although atrial dilatation is an increasingly recognised cause. Awareness of the poor prognosis associated with increasing TR severity has refocused the quest for effective treatments. Surgical intervention has been hindered by high in-hospital mortality (up to 10%), even in carefully selected cases, and transcatheter tricuspid valve interventions (TTVIs) have emerged as a low-risk alternative for this high-risk cohort. Increasing data demonstrate the clinical safety and efficacy of TTVIs, but uncertainties remain concerning optimal case selection and procedural timing. Herein, we review newly established techniques alongside emerging clinical and procedural outcome data.

BACKGROUND:Left ventricular (LV) remodeling in mitral valve prolapse (MVP) may occur disproportionally to mitral regurgitation (MR) severity, especially in patients with Barlow disease. This study hypothesized an underlying MVP cardiomyopathy, potentially driven by ventricular arrhythmias or a genetic substrate. We investigated the determinants of LV remodeling in patients with MVP beyond MR volume load. METHODS:Prospective inclusion of patients with nonsyndromic MVP at 3 centers. Patients were scheduled for cardiac magnetic resonance scans, 24-hour Holter monitoring, and the presence of an underlying cardiomyopathy-associated genetic variant was assessed. Disproportionate LV remodeling was defined as LV end-diastolic volume above the age- and sex-specific upper limit of normal after correction for the total MR volume load, using the following formula: (LV end-diastolic volume-MR volume)/body surface area-LVEDViULN >0. RESULTS:A total of 103 patients with MVP were included (58% males, age 52±17 years). Disproportionate LV remodeling was present in 37% and was more frequent in Barlow disease compared with nonclassic MVP (P=0.067). After correction for age, sex, and MR volume load, Barlow disease phenotypic features like mitral annular dilatation are independently associated with LV dilatation (P<0.001 at multivariable regression analysis for left ventricular end-systolic volume index, R2=0.518). The total volume load (MR volume+prolapse volume) had a stronger correlation with LV remodeling than MR volume alone. In addition, ventricular arrhythmia-particularly ≥3% premature ventricular contractions-was independently associated with increased left ventricular end-systolic volume index even after correction for other classical risk factors (P=0.024, R2=0.518). None of the patients carried a likely pathogenic or pathogenic variant in cardiomyopathy-associated genes. CONCLUSIONS:LV remodeling in MVP is a multifactorial process, where, especially in patients with Barlow disease, the associated mitral annular dilatation and larger prolapse volume drive LV dilatation beyond MR severity. In addition, a burden of ≥3% ventricular ectopy is strongly correlated with LV dilatation and dysfunction. Finally, a monogenic cardiomyopathy substrate appears unlikely.

Background:Mitral annular disjunction (MAD), consisting in a systolic separation between the posterior atrial wall-leaflet junction and the basal left ventricular wall, is a disputed imaging entity. MAD was initially associated with sudden cardiac death and ventricular arrhythmias in patients with mitral valve prolapse, whereas in more recent studies, it has been presented as a normal variant of the mitral annulus. Case summary:In the present series of two cases, we show a case featuring a young woman with syncope that showed a microscopic MAD on echocardiography but, after a thorough multimodality assessment, was diagnosed with a coronary anomaly responsible for her presentation. In the second case, a young man presenting with aborted sudden cardiac death was found to have a macroscopic MAD in the context of mitral valve prolapse with numerous high-risk arrhythmic features. Discussion:The need for assessing the diverse significance of MAD in the clinical and imaging context of each patient is underscored. Assessment of MAD should be complemented by other imaging and clinical parameters: the circumferential and longitudinal extent of MAD, the presence of repolarization abnormalities or ventricular arrhythmias, bi-leaflet prolapse, systolic curling, the Pickelhaube sign, left heart remodelling, and the presence of myocardial fibrosis, among others.

AIMS:Selection of the patients for implantable cardioverter defibrillator primary prevention therapy in non-ischaemic cardiomyopathy (NICM) needs to be improved. To evaluate the additional prognostic value of a new cardiac magnetic resonance (CMR) score based on late gadolinium enhancement (LGE) pattern distribution (DERIVATE Risk Score 2.0) when compared with previously published DERIVATE Risk Score 1.0, which is based solely on quantitative parameters, in a cohort of NICM patients enrolled in the DERIVATE registry. METHODS AND RESULTS:One thousand three hundred and eighty-four NICM patients with chronic heart failure and left ventricular ejection fraction (LVEF) < 50% were evaluated for primary sudden cardiac death prevention therapy. Major adverse arrhythmic cardiac events (MAACEs) were the primary endpoint. During a median follow-up of 959 days, MAACE occurred in 128 (9.2%) patients. In the multivariate analyses, male gender [hazard ratio (HR): 1.605 (95% confidence interval, CI: 1.051-2.451); P = 0.028], LVEF per point % [HR: 0.977 (95% CI: 0.961-0.993); P = 0.005] and presence and location of midwall LGE [weighted HR: 1.066 (95% CI: 1.045-1.086), P < 0.001] were independent predictors of MAACE. A multi-parametric CMR-weighted predictive-derived score (DERIVATE Risk Score 2.0) provided a higher additional prognostic value vs. transthoracic echocardiography-LVEF cut-off of 35% when compared with the previous published DERIVATE Risk Score 1.0 with a net reclassification improvement of 54.52% (95% CI: 36.52-72.52%; P < 0.001). These findings were confirmed in the validation cohort. CONCLUSION:The presence of midwall LGE, but also the location of scar, confers an added and independent MAACE risk to a large NICM population influencing the choice of treatment.

AIMS:Accurate risk stratification for patients with non-dilated left ventricular cardiomyopathy (NDLVC) remains challenging due to lack of dedicated clinical trials. This post hoc analysis aims to delineate the arrhythmic risk and assess the incremental value of cardiac magnetic resonance (CMR) imaging in the CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy (DERIVATE) study cohort meeting the NDLVC diagnostic criteria. METHODS AND RESULTS:Patients with NDLVC from the DERIVATE registry were identified in the absence of left ventricular (LV) dilatation and in the presence of non-ischaemic LV scarring ('fibrotic NDLVC') or isolated LV systolic dysfunction (LV ejection fraction < 50%) without fibrosis ('hypokinetic NDLVC'). The primary endpoint was all-cause mortality. Major adverse arrhythmic cardiac events (MAACE) were the secondary endpoint and included sudden cardiac death (SCD) and aborted SCD. One hundred and ninety-seven NDLVC patients were identified from the cohort of the DERIVATE study (mean age: 59 ± 14 years; male: 135). Over a median follow-up of 2.7 years, 15 (8%) patients died and 8 (4%) experienced MAACE. Patients with 'hypokinetic' NDLVC had significantly lower rates of MAACE than non-ischaemic dilated cardiomyopathy (NIDCM) (P = 0.001), while patients with 'fibrotic' NDLVC had same rate of both primary (P = 0.48) and secondary endpoints (P = 0.616) compared with NIDCM patients. Multivariable analysis identified late gadolinium enhancement (LGE) with midwall distribution as an independent predictor of MAACE in NDLVC patients (hazard ratio 6.7, 95% confidence interval: 1.33-33.67; P = 0.021). CONCLUSION:NDLVC patients exhibit a heterogeneous risk profile for arrhythmic events. The presence of midwall LGE, similarly to NIDCM, is a significant predictor of MAACE, highlighting the importance of CMR imaging for risk stratification.

Patients and healthcare professionals require clinical prediction models to accurately guide healthcare decisions, although an awareness of the limitations of regression-based models has recently increased. Deep learning (DL) has emerged as a promising alternative to traditional regression-based models, due to its ability to effectively analyse heterogeneous types of data, ranging from numerical variables to medical images. Building a DL model presents various challenges, including conceptualizing the clinical problem, selecting appropriate variables and model architecture, and providing explainability. We propose a four-step pipeline for developing DL-based prediction models for cardiac magnetic resonance image analysis. This framework aims to support researchers in exploring DL application across the broad spectrum of cardiology, with a specific focus on advancement in arrhythmic risk prediction. The field of cardiomyopathy faces challenges when assessing arrhythmic risk due to the low accuracy of the current prediction models. Research efforts have focused on developing DL models able to predict major arrhythmic events in dilated cardiomyopathy. While the initial results are promising, further tests are needed before translating these models into clinical practice.

Thoracic aortopathies result in aneurysmal expansion of the aorta that can lead to rapidly fatal aortic dissection or rupture. Despite the availability of abundant non-invasive imaging tools, the greatest contemporary challenge in the management of thoracic aortic aneurysm (TAA) is the lack of reliable metrics for risk stratification, with absolute aortic diameter, growth rate, and syndromic factors remaining the primary determinants by which prophylactic surgical intervention is adjudged. Advanced cardiovascular magnetic resonance (CMR) techniques present a potential key to unlocking insights into TAA that could guide disease surveillance and surgical intervention. CMR has the capacity to encapsulate the aorta as a complex biomechanical structure, permitting the determination of aortic volume, morphology, composition, distensibility, and fluid dynamics in a time-efficient manner. Nevertheless, current standard-of-care imaging protocols do not harness its full capacity. This state-of-the-art review explores the emerging role of CMR in the assessment of TAA and presents a blueprint for the required paradigm shift away from aortic size as the sole metric for risk-stratifying TAA.