Aims  Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes. Methods and results  One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson’s trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF−) median percentage MF (≥11% or <11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003). In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. 2% in MF− patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0–369), P = 0.01]. Conclusion  Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI.

Background: Right heart catheterisation (RHC) using exercise-stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiovascular magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary non-invasive alternative for diagnosing HFpEF. Methods: The HFpEF stress trial (DZHK-17, NCT03260621) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association (NYHA) class ≥II) to undergo echocardiography, RHC and RT-CMR at rest and during exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular (LV) filling, left atrial (LA) emptying and LV/LA long axis strain (LAS). Results: HFpEF patients (n=34, median PCWP rest 13mmHg, stress 27mmHg) had higher E/e' (12.5 vs. 9.15), NT-proBNP (255 vs. 75ng/l) and LA volume index (43.8 vs. 36.2ml/m 2 ) compared to non-cardiac dyspnea patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). Seven patients were excluded due to the presence of non HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164) between HFpEF and non-cardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (p<0.001) diastolic emptying in HFpEF during exercise-stress. RT-CMR exercise-stress LA LAS was independently associated with HFpEF (adjusted odds ratio 0.657, 95% confidence interval [0.516; 0.838], p=0.001) after adjustment for clinical and imaging parameters and emerged as the best predictor for HFpEF (area under the curve rest 0.82 vs. exercise-stress 0.93, p=0.029). Conclusions: RT-CMR allows highly accurate identification of HFpEF during physiological exercise and qualifies as a suitable non-invasive diagnostic alternative. These results will need to be confirmed in multi-centre prospective research studies to establish widespread routine clinical use. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03260621

Background: Cardiovascular magnetic resonance (CMR) represents the clinical gold standard for the assessment of biventricular morphology and function. Since manual post-processing is time-consuming and prone to observer variability, efforts have been directed towards automated volumetric quantification. In this study, we sought to validate the accuracy of a novel approach providing fully automated quantification of biventricular volumes and function in a "real-world" clinical setting. Methods: Three-hundred CMR examinations were randomly selected from the local data base. Fully automated quantification of left ventricular (LV) mass, LV and right ventricular (RV) end-diastolic and end-systolic volumes (EDV/ ESV), stroke volume (SV) and ejection fraction (EF) were performed overnight using commercially available software (suiteHEART®, Neosoft,

CARDIAC IMAGINGL eft ventricular (LV) ejection fraction (EF) is used to assess systolic myocardial function after acute myocardial infarction (AMI), and reduced LV EF is associated with adverse cardiovascular events (1). Risk stratification can be optimized by assessing myocardial ventricular strain with incremental value over LV EF, suggesting an important role of ventricular function imaging in patients with recent AMI (2,3).The importance of left atrial (LA) function and structure is increasingly recognized and has led to the introduction of atrial cardiomyopathy as an independent entity (4). Greater atrial volume is commonly associated with cardiovascular diseases, such as ischemic heart disease, valvular heart disease, and heart failure (eg, dilated cardiomyopathy) (5). Elevated LA volume has been shown to predict cardiovascular mortality (6) beyond LV EF after AMI (7). Volumetric atrial function shows superior predictive value beyond atrial size and LV EF in ST-elevation myocardial infarction (STEMI) (8) and non-STEMI (NSTEMI) (9). However, the superior predictive value of atrial volumetric

Myocardial strain is a well validated parameter for estimating left ventricular (LV) performance. The aim of our study was to evaluate the inter-study as well as intra- and interobserver reproducibility of fast-SENC derived myocardial strain. Eighteen subjects (11 healthy individuals and 7 patients with heart failure) underwent a cardiac MRI examination including fast-SENC acquisition for evaluating left ventricular global longitudinal (GLS) and circumferential strain (GCS) as well as left ventricular ejection fraction (LVEF). The examination was repeated after 63 [range 49‒87] days and analyzed by two experienced observers. Ten datasets were repeatedly assessed after 1 month by the same observer to test intraobserver variability. The reproducibility was measured using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Patients with heart failure demonstrated reduced GLS and GCS compared to healthy controls (-15.7 ± 3.7 vs. -20.1 ± 1.4; p = 0.002 for GLS and -15.3 ± 3.7 vs. -21.4 ± 1.1; p = 0.001 for GCS). The test-retest analysis showed excellent ICC for LVEF (0.92), GLS (0.94) and GCS (0.95). GLS exhibited excellent ICC (0.99) in both intra- and interobserver variability analysis with very narrow limits of agreement (-0.6 to 0.5 for intraobserver and -1.3 to 0.96 for interobserver agreement). Similarly, GCS showed excellent ICC (0.99) in both variability analyses with narrow limits of agreement (-1.1 to 1.2 for intraobserver and -1.7 to 1.3 for interobserver agreement), whereas LVEF showed larger limits of agreement (-14.4 to 10.1). The analysis of fast-SENC derived myocardial strain using cardiac MRI provides a highly reproducible method for assessing LV functional performance.

AimSince cardiovascular magnetic resonance feature-tracking (CMR-FT) has been demonstrated to be of incremental clinical merit we investigated the interchangeability of global left and right ventricular strain parameters between different CMR-FT software solutions.Material and methodsCMR-cine images of 10 patients without significant reduction in LVEF and RVEF and 10 patients with a significantly impaired systolic function were analyzed using two different types of FT-software (TomTec, Germany; QStrain, Netherlands). Global longitudinal strains (LV GLS, RV GLS), global left ventricular circumferential (GCS) and radial strains (GRS) were assessed. Differences in intra- and inter-observer variability within and between software types based on single and up to three repeated and subsequently averaged measurements were evaluated.ResultsInter-vendor agreement was highest for GCS followed by LV GLS. GRS and RV GLS showed lower inter-vendor agreement. Variability was consistently higher in healthy volunteers as compared to the patient group. Intra-vendor reproducibility was excellent for GCS, LV GLS and RV GLS, but lower for GRS. The impact of repeated measurements was most pronounced for GRS and RV GLS on an intra-vendor level.ConclusionCardiac pathology has no influence on CMR-FT reproducibility. LV GLS and GCS qualify as the most robust parameters within and between individual software types. Since both parameters can be interchangeably assessed with different software solutions they may enter the clinical arena for optimized diagnostic and prognostic evaluation of cardiovascular morbidity and mortality in various pathologies.

Interleukin (IL)-1β is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β levels, however, cause life-threatening inflammatory diseases, including systemic inflammatory response syndrome. In response to various danger signals, the pro-form of IL-1β is synthesized and stays in the cytoplasm unless a second signal, such as extracellular ATP, activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β. Lipopolysaccharide-primed monocytic U937 cells were stimulated with an ATP analog in the presence of natural or synthetic surfactant composed of recombinant surfactant protein (rSP)-C, palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both surfactant preparations dose-dependently inhibited IL-1β release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary mononuclear leukocytes isolated from human blood. Experiments with nicotinic antagonists, siRNA technology, and patch-clamp experiments suggested that stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit α9 results in a complete inhibition of the ion channel function of ATP receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently inhibits ATP-induced inflammasome activation and maturation of IL-1β in human monocytes by a mechanism involving nAChRs.

BackgroundCardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software.MethodsIntra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers.ResultsTraining improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC >0.86 and >0.81) and after training (ICC >0.91 and >0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance.ConclusionObserver experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance.