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Abstract Aims This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. Methods and results Sixty‐eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e′ ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short‐axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA‐PEFF and H2FPEFF scores as well as N‐terminal prohormone of brain natriuretic peptide levels (all P 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. Conclusions Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.

Abstract This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P

Abstract Cardiovascular magnetic resonance (CMR)-derived hemodynamic force (HDF) analyses have been introduced recently enabling more in-depth cardiac function evaluation. Inter-study reproducibility is important for a widespread clinical use but has not been quantified for this novel CMR post-processing tool yet. Serial CMR imaging was performed in 11 healthy participants in a median interval of 63 days (range 49–87). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, diastolic deceleration as well as atrial thrust acceleration forces. Inter-study reproducibility and study sample sizes required to demonstrate 10%, 15% or 20% relative changes of HDF measurements were calculated. In addition, intra- and inter-observer analyses were performed. Intra- and inter-observer reproducibility was excellent for all HDF parameters according to intraclass correlation coefficient (ICC) values (> 0.80 for all). Inter-study reproducibility of all HDF parameters was excellent (ICC ≥ 0.80 for all) with systolic parameters showing lower coeffients of variation (CoV) than diastolic measurements (CoV 15.2% for systolic impulse vs. CoV 30.9% for atrial thrust). Calculated sample sizes to detect relative changes ranged from n = 12 for the detection of a 20% relative change in systolic impulse to n = 200 for the detection of 10% relative change in atrial thrust. Overall inter-study reproducibility of CMR-derived HDF assessments was sufficient with systolic HDF measurements showing lower inter-study variation than diastolic HDF analyses.

Abstract Maintaining cancer patients’ exercise capacity and therefore patients’ ability to live a self-determined life is of huge importance, but little is known about major determinants. We sought to identify determinants of exercise capacity in patients with a broad spectrum of cancer types, who were already receiving cancer treatment or about to commence such therapy. Exercise capacity was assessed in 253 consecutive patients mostly suffering from advanced cancer using the 6-min walk test (6-MWT). All patients underwent echocardiography, physical examination, resting electrocardiogram, hand grip strength (HGS) measurement, and laboratory assessments. Patients were divided into two groups according to the median distance in the 6-MWT (459 m). Patients with lower exercise capacity were older, had significantly lower HGS and haemoglobin and higher values of high sensitive (hs) Troponin T and NT-proBNP (all p 0.2). Using multivariable logistic regression, we found that the presence of anaemia (odds ratio (OR) 6.172, 95% confidence interval (CI) 1.401–27.201, p = 0.016) as well as an increase in hs Troponin T (OR 3.077, 95% CI 1.202–5.301, p = 0.019) remained independent predictors of impaired exercise capacity. Increasing HGS was associated with a reduced risk of a lower exercise capacity (OR 0.896, 95% CI 0.813–0.987, p = 0.026). Screening patients for elevated hs troponin levels as well as reduced HGS may help to identify patients at risk of lower exercise capacity during cancer treatment.

Abstract Aims There is evidence to suggest that the subtype of aortic stenosis (AS), the degree of myocardial fibrosis (MF), and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Because little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as their association with adverse cardiac events following transcatheter aortic valve replacement (TAVR). Methods and results One hundred consecutive patients with severe AS and indication for TAVR were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multidetector computed tomography, and left ventricular endomyocardial biopsies at the time of TAVR. The final study cohort consisted of 92 patients with a completed study protocol, 39 (42.4%) of whom showed a normal ejection fraction (EF) high‐gradient (NEFHG) AS, 13 (14.1%) a low EF high‐gradient (LEFHG) AS, 25 (27.2%) a low EF low‐gradient (LEFLG) AS, and 15 (16.3%) a paradoxical low‐flow, low‐gradient (PLFLG) AS. The high‐gradient phenotypes (NEFHG and LEFHG) showed the largest amount of AVC (807 ± 421 and 813 ± 281 mm3, respectively) as compared with the low‐gradient phenotypes (LEFLG and PLFLG; 503 ± 326 and 555 ± 594 mm3, respectively, P LEFHG > PLFLG > NEFHG, P PLFLG 26.7% > LEFHG 15.4% > NEFHG 2.5%; P = 0.023). In patients with a high MF burden, a higher AVC was associated with a lower mortality following TAVR (P = 0.045, hazard ratio 0.261, 95% confidence interval 0.07–0.97). Conclusions MF is associated with adverse CV outcome following TAVR, which is most prevalent in low EF situations. In the presence of large MF burden, patients with large AVC have better outcome following TAVR. Conversely, worse outcome in large MF and relatively little AVC may be explained by a relative prominence of an underlying cardiomyopathy. The better survival rates in large AVC patients following TAVR indicate TAVR induced relief of severe AS‐associated pressure overload with subsequently improved outcome.

ABSTRACT: Background: Identification of increased pulmonary capillary wedge pressure (PCWP) by right heart catheterization (RHC) is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF). Recently, cardiovascular magnetic resonance (CMR) imaging estimation of PCWP at rest was introduced as a non-invasive alternative. Since many patients are only identified during physiological exercise-stress, we hypothesized that novel exercise-stress CMR-derived PCWP emerges superior compared to its assessment at rest. Methods: The HFpEF-Stress Trial prospectively recruited 75 patients with exertional dyspnea and diastolic dysfunction who then underwent rest and exercise-stress RHC and CMR. HFpEF was defined according to PCWP (overt HFpEF ≥15 mmHg at rest, masked HFpEF ≥25 mmHg during exercise-stress). CMR-derived PCWP was calculated based on previously published formula using left ventricular mass and either biplane left atrial volume (LAV) or monoplane left atrial area (LAA). Results: LAV (rest/stress: r = 0.50/r = 0.55, p

Abstract Background Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort. Methods In total, 1046 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular (LV) end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or heart failure within 12 months after the index event were defined as primary clinical endpoint. Results LACI was significantly higher in patients with MACE compared to those without MACE (p

Abstract Aims Maintaining quality of life (QoL) in patients with cancer has gathered significant interest, but little is known about its major determinants. We sought to identify determinants of QoL in patients undergoing cancer treatment as well as in treatment‐naïve patients about to commence such therapy. Methods and results QoL was assessed in 283 patients with cancer using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire. All patients underwent a battery of tests including physical examination, resting electrocardiogram, hand grip strength, and biochemistry assessment. Using multivariable logistic regression, we found that age [odds ratio (OR) 0.954, 95% confidence interval (CI) 0.916–0.994], resting heart rate (OR 1.036, 95% CI 1.004–1.068), hand grip strength (OR 0.932, 95% CI 0.878–0.990), and the presence of cachexia (OR 4.334, 95% CI 1.767–10.631) and dyspnoea (OR 3.725, 95% CI 1.540–9.010; all P

BackgroundStrain analyses derived from cardiovascular magnetic resonance-feature tracking (CMR-FT) provide incremental prognostic benefit in patients sufferring from acute myocardial infarction (AMI). This study aims to evaluate and revalidate previously reported prognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardial infarction (STEMI).MethodsOverall, 566 STEMI patients enrolled in the CONDITIONING-LIPSIA trial including pre- and/or postconditioning treatment in addition to conventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronary intervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee), and boosterpump (Ea) strain analyses, as well as left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) analyses were carried out. Previously identified cutoff values were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction, and new congestive heart failure were assessed within 12 months after the occurrence of the index event.ResultsBoth atrial and ventricular strain values were significantly reduced in patients with MACE (p

Abstract Transcatheter aortic valve replacement (TAVR) has become the standard treatment for aortic stenosis in older patients. It increasingly relies on accurate pre-procedural planning using multidetector computed tomography (MDCT). Since little is known about the required competence levels for MDCT analyses, we comprehensively assessed MDCT TAVR planning reproducibility and accuracy with regard to valve selection in various healthcare workers. 20 randomly selected MDCT of TAVR patients were analyzed using dedicated software by healthcare professionals with varying backgrounds and experience (two structural interventionalists, one imaging specialist, one cardiac surgeon, one general physician, and one medical student). Following the analysis, the most appropriate Edwards SAPIEN 3™ and Medtronic CoreValve valve size was selected. Intra- and inter-observer variability were assessed. The first structural interventionalist was considered as reference standard for inter-observer comparison. Excellent intra- and inter-observer variability was found for the entire group in regard to the MDCT measurements. The best intra-observer agreement and reproducibility were found for the structural interventionalist, while the medical student had the lowest reproducibility. The highest inter-observer agreement was between both structural interventionalists, followed by the imaging specialist. As to valve size selection, the structural interventionalist showed the highest intra-observer reproducibility, independent of the brand of valve used. Compared to the reference structural interventionalist, the second structural interventionalist showed the highest inter-observer agreement for valve size selection [ICC 0.984, 95% CI 0.969–0.991] followed by the cardiac surgeon [ICC 0.947, 95%CI 0.900–0.972]. The lowest inter-observer agreement was found for the medical student [ICC 0.507, 95%CI 0.067–0.739]. While current state-of-the-art MDCT analysis software provides excellent reproducibility for anatomical measurements, the highest levels of confidence in terms of valve size selection were achieved by the performing interventional physicians. This was most likely attributable to observer experience.

(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5′-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced.

Abstract Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively. CMR data (n = 1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n = 759) and non-STEMI (TATORT-NSTEMI n = 336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI. Manually and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08–1.16, p

Abstract Background Since cardiovascular magnetic resonance (CMR) imaging allows comprehensive quantification of both myocardial function and structure we aimed to assess myocardial remodeling processes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods CMR imaging was performed in 40 patients with severe AS before and 1 year after TAVR. Image analyses comprised assessments of myocardial volumes, CMR-feature-tracking based atrial and ventricular strain, myocardial T1 mapping, extracellular volume fraction-based calculation of left ventricular (LV) cellular and matrix volumes, as well as ischemic and non-ischemic late gadolinium enhancement analyses. Moreover, biomarkers including NT-proBNP as well as functional and clinical status were documented. Results Myocardial function improved 1 year after TAVR: LV ejection fraction (57.9 ± 16.9% to 65.4 ± 14.5%, p = 0.002); LV global longitudinal (− 21.4 ± 8.0% to -25.0 ± 6.4%, p

Cardiac anatomy and function vary considerably across the human population with important implications for clinical diagnosis and treatment planning. Consequently, many computer-based approaches have been developed to capture this variability for a wide range of applications, including explainable cardiac disease detection and prediction, dimensionality reduction, cardiac shape analysis, and the generation of virtual heart populations. In this work, we propose a variational mesh autoencoder (mesh VAE) as a novel geometric deep learning approach to model such population-wide variations in cardiac shapes. It embeds multi-scale graph convolutions and mesh pooling layers in a hierarchical VAE framework to enable direct processing of surface mesh representations of the cardiac anatomy in an efficient manner. The proposed mesh VAE achieves low reconstruction errors on a dataset of 3D cardiac meshes from over 1,000 patients with acute myocardial infarction, with mean surface distances between input and reconstructed meshes below the underlying image resolution. We also find that it outperforms a voxelgrid-based deep learning benchmark in terms of both mean surface distance and Hausdorff distance while requiring considerably less memory. Furthermore, we explore the quality and interpretability of the mesh VAE's latent space and showcase its ability to improve the prediction of major adverse cardiac events over a clinical benchmark. Finally, we investigate the method's ability to generate realistic virtual populations of cardiac anatomies and find good alignment between the synthesized and gold standard mesh populations in terms of multiple clinical metrics.

Summary: Background: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Exercise-stress testing is recommended in case of uncertainty; however, this approach is time-consuming and costly. Since preserved EF does not represent normal systolic function, we hypothesized comprehensive cardiovascular magnetic resonance (CMR) assessment of cardiac hemodynamic forces (HDF) may identify functional abnormalities in HFpEF. Methods: The HFpEF Stress Trial (DZHK-17; Clinicaltrials.gov: NCT03260621) prospectively recruited 75 patients with exertional dyspnea, preserved EF (≥50%) and signs of diastolic dysfunction (E/e’ ≥8) on echocardiography. Patients underwent rest and exercise-stress right heart catheterisation, echocardiography and CMR. The final study cohort consisted of 68 patients (HFpEF n = 34 and non-cardiac dyspnea n = 34 according to pulmonary capillary wedge pressure (PCWP)). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, E-wave deceleration as well as A-wave acceleration forces. Follow-up after 24 months evaluated cardiovascular mortality and hospitalisation (CVH) – only two patients were lost to follow-up. Findings: HDF assessment revealed impairment of LV longitudinal function in patients with HFpEF compared to non-cardiac dyspnoea (15.8% vs. 18.3%, p = 0.035), attributable to impairment of systolic peak (38.6% vs 51.6%, p = 0.003) and impulse (20.8% vs. 24.5%, p = 0.009) forces as well as late diastolic filling (−3.8% vs −5.4%, p = 0.029). Early diastolic filling was impaired in HFpEF patients identified at rest compared with patients identified during stress only (7.7% vs. 9.9%, p = 0.004). Impaired systolic peak was associated with CVH (HR 0.95, p = 0.016), and was superior to LV global longitudinal strain assessment in prediction of CVH (AUC 0.76 vs. 0.61, p = 0.048). Interpretation: Assessment of HDF indicates impairment of LV systolic ejection force in HFpEF which is associated with cardiovascular events. Funding: German Centre for Cardiovascular Research (DZHK).

BackgroundThe risk of myocarditis after mRNA vaccination against COVID-19 has emerged recently. Current evidence suggests that young male patients are predominantly affected. In the majority of the cases, only mild symptoms were observed. However, little is known about cardiac magnetic resonance (CMR) imaging patterns in mRNA-related myocarditis and their differences when compared to classical viral myocarditis in the acute phase of inflammation.Methods and resultsIn total, 10 mRNA vaccination-associated patients with myocarditis were retrospectively enrolled in this study and compared to 10 patients suffering from viral myocarditis, who were matched for age, sex, comorbidities, and laboratory markers. All patients (n = 20) were hospitalized and underwent a standardized clinical examination, as well as an echocardiography and a CMR. Both, clinical and imaging findings and, in particular, functional and volumetric CMR assessments, as well as detailed tissue characterization using late gadolinium enhancement and T1 + T2-weighted sequences, were compared between both groups. The median age of the overall cohort was 26 years (group 1: 25.5; group 2: 27.5; p = 0.57). All patients described chest pain as the leading reason for their initial presentation. CMR volumetric and functional parameters did not differ significantly between both groups. In all cases, the lateral left ventricular wall showed late gadolinium enhancement without significant differences in terms of the localization or in-depth tissue characterization (late gadolinium enhancement [LGE] enlargement: group 1: 5.4%; group 2: 6.5%; p = 0.14; T2 global/maximum value: group 1: 38.9/52 ms; group 2: 37.8/54.5 ms; p = 0.79 and p = 0.80).ConclusionThis study yielded the first evidence that COVID-19 mRNA vaccine-associated myocarditis does not show specific CMR patterns during the very acute stage in the most affected patient group of young male patients. The observed imaging markers were closely related to regular viral myocarditis in our cohort. Additionally, we could not find any markers implying adverse outcomes in this relatively little number of patients; however, this has to be confirmed by future studies that will include larger sample sizes.

Background. Cardiovascular magnetic resonance imaging is considered the reference standard for assessing cardiac morphology and function and has demonstrated prognostic utility in patients undergoing transcatheter aortic valve replacement (TAVR). Novel fully automated analyses may facilitate data analyses but have not yet been compared against conventional manual data acquisition in patients with severe aortic stenosis (AS). Methods. Fully automated and manual biventricular assessments were performed in 139 AS patients scheduled for TAVR using commercially available software (suiteHEART®, Neosoft; QMass®, Medis Medical Imaging Systems). Volumetric assessment included left ventricular (LV) mass, LV/right ventricular (RV) end-diastolic/end-systolic volume, LV/RV stroke volume, and LV/RV ejection fraction (EF). Results of fully automated and manual analyses were compared. Regression analyses and receiver operator characteristics including area under the curve (AUC) calculation for prediction of the primary study endpoint cardiovascular (CV) death were performed. Results. Fully automated and manual assessment of LVEF revealed similar prediction of CV mortality in univariable (manual: hazard ratio (HR) 0.970 (95% CI 0.943–0.997) p=0.032; automated: HR 0.967 (95% CI 0.939–0.995) p=0.022) and multivariable analyses (model 1: (including significant univariable parameters) manual: HR 0.968 (95% CI 0.938–0.999) p=0.043; automated: HR 0.963 [95% CI 0.933–0.995] p=0.024; model 2: (including CV risk factors) manual: HR 0.962 (95% CI 0.920–0.996) p=0.027; automated: HR 0.954 (95% CI 0.920–0.989) p=0.011). There were no differences in AUC (LVEF fully automated: 0.686; manual: 0.661; p=0.21). Absolute values of LV volumes differed significantly between automated and manual approaches (p