BACKGROUND:Heart failure (HF) is a significant public health concern. Early detection, particularly during the asymptomatic stage, is essential for prompt intervention and preventing progression. Conventional measures, such as left ventricular ejection fraction (LVEF) have limited sensitivity. However, left ventricular global longitudinal strain (GLS) can detect subclinical myocardial dysfunction. Preliminary data from the previous HERZCHECK study showed that 23% (1023/4509) of participants in rural Germany had GLS-defined subclinical pre-HF (stage B HF) when examined with mobile cardiac MRI units. Yet, the prevalence of asymptomatic HF in urban populations remains unclear. The WE-CARE-HF-CMR trial aims to address this issue. STUDY DESIGN AND METHODOLOGY:The WE-CARE-HF-CMR trial is a single-center prospective observational study with a cross-sectional baseline assessment and an exploratory longitudinal follow-up conducted in five urban German cities (Berlin, Cologne, Frankfurt, Hamburg, Munich; NCT07185100). Asymptomatic patients between the ages of 40 and 69 with cardiovascular risk factors but without a history of symptomatic HF are enrolled via outpatient physician referral or self-referral. Participants undergo a standardized diagnostic evaluation including a medical history review, laboratory testing, cardiovascular magnetic resonance (CMR) imaging with GLS analysis, and quality-of-life questionnaires. CMR examinations are performed using both stationary and mobile magnetic resonance imaging (MRI) units. Subclinical pre-HF (stage B HF) is defined as GLS ≥ -15%. The primary endpoint is the prevalence of subclinical pre-HF (stage B HF) in the urban population. Secondary endpoints assess therapy adherence, quality of life, and the prevalence of chronic kidney disease. CMR images are analyzed centrally following standardized protocols to ensure comparability with HERZCHECK rural data. CONCLUSION:The WE-CARE-HF-CMR trial will provide critical data on the prevalence of subclinical pre-HF (stage B HF) in urban populations. Using CMR-based GLS analysis with stationary and mobile units, and building on the HERZCHECK trial methodology, the study will close the diagnostic gap between rural and urban areas. These findings may ultimately support the implementation of targeted screening programs for subclinical pre-HF (stage B HF) to enable early intervention and prevent the progression to symptomatic HF. CLINICALTRIALS: GOV IDENTIFIER:NCT07185100.

Abstract Persistent cardiac symptoms are common in post-COVID syndrome, even without structural heart disease. Evidence implicates immune dysregulation, endothelial dysfunction and low-grade cardiovascular inflammation. Yet no targeted treatment exists. Myoflame-19 is a multicenter, double-blind clinical trial of 279 participants with inflammatory cardiac involvement defined by cardiovascular magnetic resonance, randomized 1:1 to losartan plus prednisolone ( n = 139 ) or matching placebos ( n = 140 ) for 16 weeks. The modified intention-to-treat population comprised 124 and 122 participants. The primary endpoint, change in left ventricular (LV) ejection fraction, was neutral: between-group difference 0.74 percentage points (pp), 95%CI −0.14 to 1.62, p = 0.10, unpaired t-test; supportive baseline-adjusted ANCOVA 0.99, 95%CI 0.15-1.83, p = 0.021. Among prespecified secondary endpoints, several symptom and imaging measures showed numerical differences favoring intervention, including Average Symptom Score components (modified Canadian Chest Pain Scale −4.8 pp, 95%CI −17.3 to 7.6; NYHA class −8.1 pp, −20.6 to 4.3; Long COVID symptom burden −7.7 pp, −18.9 to 3.6), native T1 and T2 values (native T1 −2.46 ms, −8.35 to 3.42; native T2 −0.31 ms, −1.16 to 0.53), and LV end-diastolic volume ( + 1.45 ml/m², −0.09 to 3.00); however, confidence intervals included the null value and these findings should be regarded as hypothesis-generating.Treatment was safe and well-tolerated. These findings indicate a neutral treatment effect on the primary endpoint. They inform targeted immunomodulation and design of future trials in post-COVID syndrome and inflammatory cardiac involvement. Trial registration: EudraCT 2022-001682-12; NCT05619653.

BACKGROUND:There is a growing consensus that screening for subclinical preheart failure (HF) may reduce the burden of symptomatic HF by allowing for timely preventive interventions. However, validated screening algorithms are currently lacking. The aim of this study was to evaluate a fully mobile telemedically supervised cardiac magnetic resonance, as a simple standardized, and ubiquitously applicable screening algorithm for subclinical pre-HF in rural and underresourced regions. METHODS:HERZCHECK was a cross-sectional cohort study conducted at 12 sites across rural and underresourced regions of Germany. Asymptomatic participants (40-69 years) with ≥1 cardiovascular risk factor-obesity, smoking, arterial hypertension, diabetes, hypercholesterolemia, or chronic kidney disease-were enrolled and underwent telemedically supervised contrast-free short cardiac magnetic resonance in mobile screening units. Subclinical pre-HF was diagnosed using a predefined cutoff of global longitudinal strain ≥-15%. A matched and entropy-balanced control cohort constructed from claims data was used to determine the time difference between detection of subclinical pre-HF in HERZCHECK and the first symptom-based diagnosis of HF within the standard of care. RESULTS:Between June 2021 and April 2023, 4666 participants were enrolled in the study, of which 4509 participants were included in the final analysis. The prevalence of subclinical pre-HF in the studied at-risk population was 22.7% (95% CI, 21.5%-23.9%). Global longitudinal strain-based screening identified subclinical pre-HF 6.7 years before the average onset of symptomatic HF within the standard of care (n=8420). CONCLUSIONS:Subclinical pre-HF affects approximately one-fourth of the at-risk population in rural and underresourced regions. The HERZCHECK approach identifies patients suitable for targeted preventive interventions ≈7 years earlier than the standard of care. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05122793.

BACKGROUND:Exercise intolerance is a common and incapacitating long-term consequence of coronavirus disease (COVID-19), even after mild acute illness. Cardiovascular magnetic resonance (CMR) studies have demonstrated persistent perimyocardial inflammatory abnormalities; however, their relationship with long-term aerobic capacity remains unclear. METHODS:In this prospective observational study, individuals without prior structural heart disease underwent standardized CMR, echocardiography, and cardiopulmonary exercise testing (CPET) at least 3 years after the initial COVID-19. The primary endpoint was the association between %-predicted peak oxygen consumption (VO₂peak) (age-sex-body mass index (BMI) adjusted, Study of Health in Pomerania (SHIP) https://doi.org/10.1007/s00103-012-1483-6) and imaging parameters. Secondary analyses included lactate measurements and sex-stratified models. RESULTS:A total of 132 participants (mean age 49±12 years; 68/132 (52%) male) were evaluated 48 months [interquartile range (IQR) 42-53] post-infection. Non-ischemic perimyocardial enhancement was present in 34/132 (26%), whereas two participants had an unrecognized ischemic scar. Male sex, higher BMI, lower age, and higher native T1 were associated with lower %-predicted VO₂peak in univariate models. In multivariate analysis, male sex, lower age, and higher native T1 (β = -0.25 per ms, 95% CI -0.40 to -0.10; p<0.001) remained independent predictors of lower %-predicted VO₂peak. In total, 63/132 (48%) participants demonstrated %-predicted VO₂peak below predicted values. Sex-stratified multivariate analyses showed that higher native T1 (p<0.001) independently associated with lower %-predicted VO₂peak in both men and women, with lower age additionally retained in men. In a lactate-measured subgroup (n = 73), higher resting lactate, higher native T1, male sex, and lower left atrial area were associated with lower %-predicted VO₂peak. CONCLUSION:In long-term follow-up of individuals with mild initial COVID-19 and no prior structural heart disease, aerobic capacity relative to predicted values was reduced in 48% of participants, particularly in men, and was independently associated with higher myocardial native T1.

BACKGROUND:Diabetes mellitus (DM) promotes myocardial remodeling through advanced glycation end-products, interstitial fibrosis, and microvascular dysfunction. We investigated whether native T1 mapping captures this adverse phenotype and provides incremental prognostic information beyond established clinical risk factors in a real-world population. METHODS:Patients undergoing CMR were enrolled in a prospective single-center all-comer registry. CMR parameters were compared between groups, adjusted for LV end-diastolic volume index and major fibrosis-inducing comorbidities. Prognostic significance for the composite endpoint of all-cause mortality, heart failure hospitalization, and appropriate ICD shock therapy was assessed using Cox regression. Incremental value was evaluated by likelihood-ratio testing, IDI, and NRI. RESULTS:Among 3614 patients (DM n = 635, 18%), DM patients showed higher native T1 and impaired GLS (1137 ms [1134-1139] vs. 1147 ms [1141-1153], p < 0.001; -16.05% [-16.2 to -15.9] vs. -13.8% [-14.2 to -13.4], p < 0.001). The T1 difference persisted after adjustment for fibrosis-inducing comorbidities. In the multivariable model (N = 2426, 82 events), native T1 and lower LVEF were independently associated with outcomes. GLS was independently prognostic only when replacing LVEF. DM patients with T1 > 1123 ms showed the poorest prognosis. Adding native T1 improved global model fit (LR χ2 = 7.94, p = 0.0048), discrimination (C-index 0.758 → 0.771), reclassification (NRI = 0.113, p = 0.013). CONCLUSIONS:Patients with DM exhibit distinct structural and functional myocardial phenotypes. Native T1 captures diffuse myocardial alterations associated with adverse outcomes and provides modest incremental prognostic information beyond established clinical risk factors within the observed follow-up period, supporting comprehensive CMR phenotyping for risk stratification in DM.

Purpose Approximately 30% of patients with atrial fibrillation (AF) develop heart failure (HF), but the underlying mechanisms and their impact on the left ventricle (LV) remain unclear. Fibrosis and inflammation are suspected contributors. This study aimed to investigate LV tissue characteristics in patients with and without AF using cardiac magnetic resonance imaging (CMR). Methods Patients from a single-center CMR registry were categorized by AF status, adjudicated by two blinded investigators. LV fibrosis was assessed by native T1 and extracellular volume (ECV), while T2 indicated inflammation. Results were adjusted for LV ejection fraction (LVEF), end-systolic volume index (ESVi), and late gadolinium enhancement mass (LGEmass). Prognostic value was tested with multivariable Cox regression, using all-cause mortality or HF hospitalization at one year as the endpoint. Results Of 2,879 patients with one-year follow-up, 590 had AF. They showed lower LVEF and higher ESVi and LGEmass. After adjustment, AF was linked to higher T1 (p = 0.006), T2 (p = 0.01), and ECV (p < 0.001). Eighty-five patients reached the endpoint. In multivariable analysis, only T1 independently predicted outcome. Kaplan-Meier analysis showed patients with T1 above the median (1125 ms) had worse outcomes than those below, even without AF. The combination of AF and elevated T1 carried the poorest prognosis (p = 0.001). Conclusion AF is closely associated with LV fibrosis and inflammation, with T1 emerging as an independent predictor of outcome. These findings suggest a mechanistic pathway with important prognostic implications. Prospective studies are warranted to confirm these associations and explore their role in patient stratification and management.

Myocardial inflammation is a key driver of adverse outcomes; yet its clinical recognition remains challenging because of heterogeneous presentation and non-standardised prognostic frameworks. While prior studies linked troponin and late gadolinium enhancement (LGE) by cardiovascular magnetic resonance imaging (CMR) to outcomes, the relative prognostic value of individual non-invasive markers has not been systematically evaluated. We systematically evaluated the prognostic value of biomarkers and non-invasive imaging variables in patients with clinically suspected myocardial inflammation presenting to tertiary centres and referred for CMR diagnostic evaluation. The primary endpoint was major adverse cardiovascular events (MACE). A total of 722 patients (median age: 50 years [IQR: 40–61]; 422 males [58

Purpose Federated training is often challenging on heterogeneous datasets due to divergent data storage options, inconsistent naming schemes, varied annotation procedures, and disparities in label quality. This is particularly evident in the emerging multi-modal learning paradigms, where dataset harmonization including a uniform data representation and filtering options are of paramount importance.Methods DICOM-structured reports enable the standardized linkage of arbitrary information beyond the imaging domain and can be used within Python deep learning pipelines with highdicom. Building on this, we developed an open platform for data integration with interactive filtering capabilities, thereby simplifying the process of creation of patient cohorts over several sites with consistent multi-modal data.Results In this study, we extend our prior work by showing its applicability to more and divergent data types, as well as streamlining datasets for federated training within an established consortium of eight university hospitals in Germany. We prove its concurrent filtering ability by creating harmonized multi-modal datasets across all locations for predicting the outcome after minimally invasive heart valve replacement. The data include imaging and waveform data (i.e., computed tomography images, electrocardiography scans) as well as annotations (i.e., calcification segmentations, and pointsets), and metadata (i.e., prostheses and pacemaker dependency).Conclusion Structured reports bridge the traditional gap between imaging systems and information systems. Utilizing the inherent DICOM reference system arbitrary data types can be queried concurrently to create meaningful cohorts for multi-centric data analysis. The graphical interface as well as example structured report templates are available at https://github.com/Cardio-AI/fl-multi-modal-dataset-creation .

AIMS:The diagnostic performance of quantitative perfusion cardiac magnetic resonance (QP-CMR) imaging has scarcely been evaluated in patients with a history of coronary artery disease (CAD) and new onset chest pain. The present study compared the diagnostic performance of automated QP-CMR for the detection of fractional flow reserve (FFR) defined hemodynamically significant CAD with visual assessment of first-pass stress perfusion CMR (v-CMR) and quantitative [15O]H2O positron emission tomography (PET) imaging in a true head-to-head fashion in patients with prior CAD. METHODS AND RESULTS:This PACIFIC-2 substudy included 145 symptomatic chronic coronary symptom patients with prior myocardial infarction and/or percutaneous coronary intervention. All patients underwent dual-sequence, single-bolus perfusion CMR, and [15O]H2O PET perfusion imaging followed by invasive coronary angiography with three-vessel FFR. Hemodynamically significant CAD was defined as an FFR ≤ 0.80. QP-CMR, v-CMR, and PET exhibited a sensitivity of 66, 67, and 80%, respectively, whereas specificity was 60, 62, and 63%. Sensitivity of QP-CMR was lower than that of PET (P = 0.015), whereas the specificity of QP-CMR and PET was comparable. Diagnostic accuracy and area under the curve of QP-CMR (64% and 0.66) was comparable to both v-CMR [66% (P = not significant [NS]) and 0.67 (P = NS)] and PET [74% (P = NS) and 0.78 (P = NS)]. CONCLUSION:In patients with prior myocardial infarction and/or percutaneous coronary intervention, the diagnostic performance of QP-CMR was comparable to visual assessment of first-pass stress perfusion CMR and quantitative [15O]H2O PET for the detection of hemodynamically significant CAD as defined by FFR.

The aim of this study was to evaluate the subclinical patterns and evolution of cardiac abnormalities via transthoracic echocardiography (TTE) in patients with mild initial COVID-19 illness. A total of 343 infected individuals (163 males; age 44 (interquartile range, IQR 35–52) years) years) underwent serial TTE assessments at a median of 109 (interquartile range (IQR), 77–177) and 327 (276–379) days after infection. Compared with those of non-COVID-19-infected controls (n = 94, male n = 49), baseline systolic (LVEF, TAPSE) and diastolic function (eʹ, aʹ, E/eʹ) were significantly different in infected participants (p < 0.05 for all). Compared with baseline assessments, there was a reduction in global longitudinal strain (GLS) and an increase in the E wave, E/A ratio and E/eʹ at follow-up. At baseline, symptomatic participants had a lower LVEF and TAPSE and increased IVRT, eʹ and E/eʹ. At follow-up, symptomatic patients had a lower LV end-diastolic diameter (LVEDd). Symptoms were independently associated with E/eʹ at baseline (OR (95% CI) 1.45 (1.12–1.87), p = 0.005). Symptoms at follow-up were associated with LVEDd, measured either at baseline (OR: 0.91 (0.86, 0.96), p < 0.001) or follow-up (OR (95% CI) 0.91 (0.86–0.96), p < 0.001). There were significant associations for GLS and troponin and E/eʹ with CRP and NTproBNP at baseline. In the present cohort of COVID-19-infected individuals with mild initial illness, echocardiographic measurements revealed significant yet subclinical differences in systolic and diastolic function compared with controls, as well as between individuals with cardiac symptoms and those without. All the measured differences were small in magnitude and thus unlikely to be detectable clinically at the individual level.

Cardiovascular inflammatory involvement is an increasingly recognized sequela of COVID-19 disease. Cardiac magnetic resonance imaging (CMR) studies recorded subtle myocardial inflammatory changes, non-ischemic myocardial late gadolinium enhancement and pericarditis, also in previously well individuals with a mild initial course of disease. To investigate the long-term cardiovascular consequences of COVID-19 on exercise intolerance and other symptoms using advanced CMR imaging and cardiopulmonary exercise testing (CPET). We report preliminary results from a subcohort of a prospective, longitudinal study. All subjects were reevaluated at least 3 years after the first documented COVID-19. None of the patients had previously known or had evidence of structural heart disease in previous CMR performed after a minimum of 4 weeks and 6 months. All subjects underwent standardised contrast-enhanced CMR scan at 3 Tesla (gadobutrol 0.1 mmol/kg), echocardiography and CPET. Significant myocardial ischemia was evaluated in all subjects using a vasodilatory myocardial perfusion test. The primary endpoint was a univariate predictive association between the maximal rate of oxygen consumption attainable during physical exertion by VO2max and the imaging measures. A total of 138 individuals were included (mean age 49±12 years, 61 males), the median time from the first infection, median [IQR], months: 45 [39, 49]). On average, the subjects were normotensive and normocardic at rest. They had normal cardiac volumes and biventricular ejection fraction. About a quarter (24%) had persistent myocardial LGE, of which one patient had an ischemic scar, not observed previously. In univariate analyses (Table 1), the independent predictors of VO2max for the study cohort during the follow-up were age, female sex, BMI, native T1, LVEDVi, RVEF and E/e’, whereas in multivariate analysis these were age, native T1 and LVEDVi. In subanalyses for gender, in males, in multivariate analysis LA area was the sole predictor of VO2max during the follow-up, while in the females, these were age, BMI and native T1. Figure 1 shows that VO2max values of post-COVID-19 patients were lower compared to the expected VO2max values based on the cardiorespiratory fitness reference database FRIEND, with a statistically significant positive correlation. Furthermore, the native T1 showed inverse correlation with VO2max values in the study cohort. In individuals without previously known structural heart disease and mild initial COVID-19 disease, age, female sex, BMI, LVEDVi, RVEF, E/e', and native T1 were univariate predictors of VO2max at long-term follow-up. In multivariate analysis age, LVEDVi and native T1 were independent predictors of VO2max at follow-up. Patients with a history of COVID-19 achieved lower VO2max values compared to the reference values measured in the FRIEND registry. Native T1 showed an inverse correlation with VO2max values. Figure 1

Cardiometabolic diseases encompass a group of conditions characterized by metabolic and inflammatory abnormalities that increase the risk of diabetes and cardiovascular disease. These syndromes involve multiple organs, including the heart, arterial system, brain, skeletal muscle, adipose tissue, hematopoietic system, liver, kidneys, and pancreas. The crosstalk between these organs contributes to the development of disease. Advances in imaging techniques, such as magnetic resonance imaging, magnetic resonance spectroscopy, computed tomography, and positron emission tomography, have revolutionized the evaluation of these conditions. Hybrid imaging modalities, such as positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging, provide unique insights into the anatomy and metabolic alterations occurring in response to cardiometabolic risk factors. These methods are particularly valuable for assessing multisystemic involvement and interorgan crosstalk, revealing critical interactions such as the brain-heart axis, the heart-liver axis, and the fat-muscle-heart dynamics. This review discusses the role of state-of-the-art imaging techniques in evaluating the pathophysiological mechanisms underlying these complex syndromes and the clinical applications of the different imaging techniques in the assessment of cardiometabolic diseases.

INTRODUCTION:Coronary artery disease is the main cause of mortality worldwide mandating early detection, appropriate treatment, and follow-up. Noninvasive cardiac imaging techniques allow detection of obstructive coronary heart disease by direct visualization of the arteries or myocardial blood flow reduction. These techniques have made remarkable progress since their introduction, achieving high diagnostic precision. This review aims at evaluating these noninvasive cardiac imaging techniques, rendering a thorough overview of diagnostic decision-making for detection of ischemia. AREAS COVERED:We discuss the latest advances in the field such as computed tomography angiography, single-photon emission tomography, positron emission tomography, and cardiac magnetic resonance; their main advantages and disadvantages, their most appropriate use and prospects. For the review, we analyzed the literature from 2009 to 2024 on noninvasive cardiac imaging in the diagnosis of coronary artery disease. The review included the 78 publications considered most relevant, including landmark trials, review articles and guidelines. EXPERT OPINION:The progress in cardiac imaging is anticipated to overcome various limitations such as high costs, radiation exposure, artifacts, and differences in interpretation among observers. It is expected to lead to more automated scanning processes, and with the assistance of artificial intelligence-driven post-processing software, higher accuracy and reproducibility may be attained.

Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases and is characterised by reduced pericyte coverage. While the contributions of other cardiac cell types to HFpEF are well-studied, the role of pericytes remains less understood. Using murine single-nucleus RNA-sequencing to study cardiac pericytes in HFpEF, we identified reduced STAT3 expression as a hallmark of HFpEF pericytes. Mechanistic studies in vitro revealed that STAT3 deletion induces cellular senescence and impairs pericyte adhesion, recapitulating HFpEF-like characteristics. These findings suggest that STAT3 is crucial for maintaining pericyte homeostasis and highlight its reduction as a potential driver of pericyte loss, a defining feature of HFpEF.