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Background Temporary epicardial pacing wires, implemented in patients during heart transplantation, are routinely removed before discharge. However, in some cases, these wires may remain in situ and are often considered as a contraindication for cardiovascular magnetic resonance (CMR) imaging in the future. Therefore, we aimed to provide data about safety and image quality of CMR in these patients. Methods This is a report on a subpopulation out of 88 patients after heart transplantation that were included in a prospective cohort study and underwent multiple CMR in their post-transplant course. During CMR, patients were monitored by electrocardiogram and all examinations were observed by a physician to document potential adverse events. Additionally, image quality was assessed by an imaging specialist. Results Nineteen of 88 patients included had temporary pacing wires in situ. These patients underwent a total of 51 CMR studies. No major adverse event and only one single, mild sensory event could be documented. All CMR studies showed preserved diagnostic image quality. Temporary pacing wires were visible in 100% of HASTE and cine sequences. In less than 50% of the examinations, temporary pacing wires were also visible in T1 and T2 mapping, short tau inversion recovery (STIR), and late gadolinium enhancement (LGE) sequences, without any impairment of image quality. Conclusions With a low event rate of only one mild adverse event during 51 CMR examinations (2%), CMR appears to be safe in patients with retained temporary epicardial pacing wires after heart transplantation. Moreover, image quality was not impaired by the presence of pacing wires.

ZusammenfassungIn der folgenden Übersicht sollen die verschiedenen Belastungsformen sowie deren Indikationen und Kontraindikation beschrieben werden. Zur Beurteilung, ob eine hämodynamisch wirksame koronare Herzkrankheit vorliegt bzw. ob eine Koronargefäßstenose hämodynamisch auch signifikant ist, dient die Myokardszintigrafie unter Belastung, welche dann der Ruheuntersuchung gegenübergestellt wird. Die Untersuchung ist allerdings nur dann auch aussagekräftig, wenn eine entsprechende Belastung der Applikation des Radiopharmakons vorausgegangen ist. Dies setzt voraus, dass die Belastung – ergometrisch oder pharmakologisch – adäquat durchgeführt wurde. Es muss der Blutfluss unter physiologischen Bedingungen bei Belastung auf das 3 – bis 4-Fache ansteigen. Dies ist das Ziel der Belastung, deren unterschiedliche Formen in der Folge beschrieben werden 1.

Objectives Within the presented prospective study, we aimed to illuminate the effect of long-term physical exercise on serum levels of adipsin (complement factor D) and angiopoietin-like 4 (ANGPTL4). Although past studies already outlined the effects of acute exercise, our trial design aimed to depict the development under long-term physical activity conditions. Design & methods 98 participants were included in the study and were asked to perform eight months of moderate physical activity for at least 150 minutes/week and/or vigorous-intensity exercise for at least 75 minutes/week. According to initial performance and performance gain throughout the study period, four groups were formed and subsequently compared. Blood sampling for the determination of routine laboratory parameters was done at baseline, after 2, 6, and 8 months. Additionally, adipsin and ANGPTL4 serum levels were concurrently quantified using commercially available ELISA kits. Results The study cohort consisted of 61.2% male participants with an average age of 49.3±6.7 years. Adipsin and ANGPTL4 were found to be strongly increased by long-term physical exercise. Participants displaying a performance gain of > 2.9% throughout the study showed significantly increased serum levels of both biomarkers. Conclusions Serum levels of adipsin and ANGPTL4 were closely tied to the individual performance gain of the participating probands. An association of adipsin levels, initial performance, and serum triglycerides was found at baseline. Interestingly, this interrelationship was not detectable after eight months of physical training. This finding might indicate adipsin's involvement in linking triglyceride-balance to individual performance and energy demands in a homeostatic state.

Background: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the vascular endothelium in several organs. Methods: Three Fabry disease patients were screened using a micro-RNA screen. An in vitro approach in human endothelial cells was used to determine miRNA regulation by Gb3. Results: In a micro-RNA screen of three Fabry patients undergoing enzyme replacement therapy, we found that miRNAs let-7a and let-7d were significantly increased after therapy. We demonstrate in vitro in endothelial cells that Gb3 induced activation of NF-κB and activated downstream targets. In addition, NF-κB activity directly reduced let-7a and let-7d miRNA expression as inhibiting NF-kB nuclear entry abolished the Gb3 effects. Conclusion: We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.

Introduction About 50% of Fabry disease (FD) patients develop cardiac manifestation, also known as Fabry cardiomyopathy. Beside echocardiography, cardiac magnetic resonance imaging (CMR) is included in the regular assessment of these patients, allowing non-invasive tissue characterization via T1 Mapping but also evaluation of morphological and functional characteristics. Purpose Myocardial strain measured by feature-tracking CMR has been previously shown to be a sensitive indicator of mechanical dysfunction in different diseases. We therefore evaluated changes of these parameters over the time, potentially reflecting disease progression in patients with FD. Furthermore, we also assessed the association of T1 mapping with follow-up changes of myocardial strain. Thus, our data may provide novel insights about cardiac changes in the natural course of the disease and cardiac effects of specific therapies. Methods We used post processing software for CMR to analyze baseline and follow-up cardiac involvement in a cohort of FD patients who were enrolled in the KarMA study, which examines cardiac changes over time. We measured left ventricular mass (LVM), left ventricular end-systolic and end-diastolic volume (LVEDV, LVESV), left ventricular ejection fraction (LVEF), mean left ventricular T1 relaxation times (T1), global longitudinal strain (GLS), global regional strain (GRS) and global circumferential strain (GCS). Statistical analyses included T-test and Spearman's correlation. Results CMR Images of 33 Patients were analyzed (22 females; mean age 40.8±16.3 years; at baseline 17 were therapy naïve and 16 on ERT), of whom 31 underwent a second CMR. In 18 patients (10 females; 44.9±16.0 years) myocardial strain measurement by feature-tracking was possible in both examinations. T1, LVM, LVEDV and LVESV, LVEF as well as GLS, GRS and GCS showed no significant change during the mean follow-up period of 43 (±17) months in all patients. However, we found a significant correlation of baseline T1 (967±84.5ms) with follow up values of LVM (84.9±32.7 g/m2; p=0.02, ρ=−0.462), LVEDV (63.0±17.6 g/m2 p=0.049 ρ=−0.398) and GRS (70.2±14.2% p=0.011 ρ=−0.5). Baseline T1 also correlated with changes in LVM (p=0.036 ρ=−0.44) and changes of GCS (p=0.001 ρ=−0.858) from baseline to follow up. Differences in T1 from baseline to follow up correlated with follow-up values of GLS (−19.5±3.57 p=0.044, ρ=−0.414) and GRS (69.1±18.7 p=0.003, ρ=−0.588). Conclusion T1, reflecting glycosphingolipid accumulation might predict changes in LVM, LVEDV and strain. Moreover, changes in T1, reflecting myocardial remodeling, go in parallel with worse left ventricular function shown by more positive values of GLS, GCS and GRS. T1 mapping together with strain parameters are important markers for monitoring patients with FD. Funding Acknowledgement Type of funding source: None

Background Data on cardiac remodeling in athletes are conflicting and rarely available in veteran athletes. Purpose Therefore, in this study we aimed to define echocardiographic features of healthy endurance athletes older than 50 years. Methods We included probands aged >50 years, who have performed endurance sports at 70% of their maximum heart rate for at least 1 hour 3 times per week over the previous 5 years. Results Between November 2018 and May 2019, 69 probands were recruited. Median age was 57 years (IQR 52–64) and 26% were female. Groups were formed according to the median training time of 6 hours per week: (A) 45 probands with ≥6 hours (IQR 6–10) and (B) 24 probands with Global right and left ventricular (LV) strain were similar, but LA reservoir strain was higher in group A than in B (27% (IQR 22–34) vs. 20% (IQR 15–29), p=0.016). Conclusion Endurance training in healthy athletes older than 50 years does not result in relevant chamber dilatation or LV hypertrophy and a weekly training duration of ≥6 hours seems beneficial to preserve diastolic function associated with an increased LA reservoir function. Funding Acknowledgement Type of funding source: None

Background Concomitant secondary atrioventricular regurgitation is frequent in patients with severe aortic stenosis scheduled fortranscatheter aortic valve replacement (TAVR). The future implications of leaving associated valve lesions untreated after TAVR remain unknown. Aim of the present study wasto characterize the evolution of concomitant secondary atrioventricular regurgitations and to evaluate their impact on long-term prognosis. Methods We prospectively enrolled 429 consecutive TAVR patients. All patients underwent comprehensive clinical, laboratory, and echocardiographic assessments prior to TAVR, at discharge, and yearly thereafter. All-cause mortality was chosen as primary study endpoint. Results At baseline, severe concomitant secondary mitral regurgitation (sMR) was present in 54 (13%) and severe concomitant secondary tricuspid regurgitation (sTR) in 75 patients (17%). After TAVR 59% of patients with severe sMR at baseline experienced sMR regression, whereas analogously sTR regressed in 43% of patients with severe sTR at baseline. Persistence of sTR and sMR were associated with excess mortality after adjustment for our bootstrap-selected confounder model with an adjusted HR of 2.44 (95% CI 1.15–5.20, P=0.021) for sMR and of 2.09 (95% CI 1.20–3.66, P=0.01) for sTR (Figure 1). Furthermore patients showing regression of atrioventricular regurgitation exhibited survival rates indistinguishable to those seen in patients without concomitant atrioventricular regurgitation (sMR: P=0.83; sTR: P=0.74) Conclusion Concomitant secondary atrioventricular regurgitation in patients with severe AS is a highly dynamic process with up to half of all patients showing regression of associated valvular regurgitation after TAVR and subsequent favorable post-interventional outcome. Persistent atrioventricular regurgitation is a major determinant of TAVR futility and proposes a window of early sequel intervention. Funding Acknowledgement Type of funding source: None

Aims Concomitant secondary atrioventricular regurgitation is frequent in patients with severe aortic stenosis scheduled for transcatheter aortic valve replacement (TAVR). The future implications of leaving associated valve lesions untreated after TAVR remain unknown. Aim of the present study was to characterize the evolution of concomitant secondary atrioventricular regurgitations and to evaluate their impact on long-term prognosis. Methods and results We prospectively enrolled 429 consecutive TAVR patients. All patients underwent comprehensive clinical, laboratory, and echocardiographic assessments prior to TAVR, at discharge, and yearly thereafter. All-cause mortality was chosen as primary study endpoint. At baseline, severe concomitant secondary mitral regurgitation (sMR) was present in 54 (13%) and severe concomitant secondary tricuspid regurgitation (sTR) in 75 patients (17%). After TAVR 59% of patients with severe sMR at baseline experienced sMR regression, whereas analogously sTR regressed in 43% of patients with severe sTR. Persistence of sTR and sMR were associated with excess mortality after adjustment for our bootstrap-selected confounder model with an adjusted HR of 2.44 (95% CI 1.15–5.20, P = 0.021) for sMR and of 2.09 (95% CI 1.20–3.66, P = 0.01) for sTR. Patients showing regression of atrioventricular regurgitation exhibited survival rates indistinguishable to those seen in patients without concomitant atrioventricular regurgitation (sMR: P = 0.83; sTR: P = 0.74). Conclusion Concomitant secondary atrioventricular regurgitation in patients with severe AS is a highly dynamic process with up to half of all patients showing regression of associated valvular regurgitation after TAVR and subsequent favourable post-interventional outcome. Persistent atrioventricular regurgitation is a major determinant of unfavourable outcome after TAVR and proposes a window of early sequel intervention.

Purpose Cardiovascular disease and foremost coronary heart disease (CHD) are the worldwide leading causes of death. The aim of this study was to use non-invasive, multimodel retinal imaging to define microvascular features in patients with and without coronary angiography (CA)-confirmed CHD. Methods In this prospective, cross-sectional pilot study we included adult patients who presented to a tertiary referral center for elective CA due to suspected CHD. All patients underwent widefield fundus photography for retinopathy grading. Optical coherence tomography angiography was used to measure vessel density (VD) of the individual capillary plexuses in 6 × 6-mm macular volume scans. Adaptive optics imaging was performed to assess the first-order arteriolar lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and wall cross-section area, as well as to qualitatively describe vessel morphology. Results Of the included 45 patients (13 females; 65 ± 10 years old), 27 were confirmed with CHD in elective CA. The most prevalent retinal vascular pathologies were arteriovenous nickings, focal arterial narrowings, and microaneurysms. VD in the superficial capillary plexus, deep capillary plexus, and choriocapillaris was lower in CHD patients, although the odds ratios were not significantly different from 1 (P = 0.06-0.92). Median arterial LD, TD, and WLR values were 98.3 µm (interquartile range [IQR] = 13.0), 122.9 µm (IQR = 17.6), and 0.26 µm (IQR = 0.07), respectively, with a trend toward a higher WLR in CHD patients. Conclusions In a cardiovascular risk population, high-resolution quantitative and qualitative microvascular phenotyping in the retina may provide valuable subclinical indicators for coronary artery impairment, although larger clinical trials are needed. Translational relevance Subclinical retinal microvascular changes may serve as non-invasive, cost-effective biomarkers for risk stratification of patients with CHD.

OnBehalf Constantin Gatterer Introduction Fabry disease (FD) is one of the most common lysosomal storage diseases caused by deficiency of Alpha-Galactosidase A and accumulation of glycosphingolipids in all cells containing lysosomes. Cardiac involvement is characterized by left ventricular hypertrophy, conduction abnormalities and myocardial fibrosis with consecutive cardiomyopathy in late stages. Purpose As the detection of early signs of cardiac involvement is crucial for the initiation of enzyme replacement therapy (ERT) or Chaperon therapy, we intended to find early imaging markers. Methods Cardiac MRI (CMR) including Late Gadolinium Enhancement (LGE), representing fibrosis, and T1-mapping as well as echocardiography with measurement of global longitudinal strain (GLS) were done as part of the regular check-ups for patients with FD. Results The study cohort of 30 FD patients (20-69 years, 53% women) in different stages of disease showed low GLS values already at the time of baseline echocardiography (mean: -17,22%), correlating with the amount of LGE (r = 0,73; p = 0,003) and ejection fraction measured by CMR (CMR-EF; r=-0,74; p = 0,002). After an average follow-up of 39 months (STD 18), GLS values were significantly declined (-15,51 %; p = 0,009) and correlated with T1 times (r = 0,7; p = 0,04), while LGE and CMR-EF did not significantly change compared to baseline. Baseline T1 times correlated negatively with the reduction of GLS (r=-0,7; p = 0,003), while LGE and CMR-EF showed no correlation with the course of GLS. ERT appeared to have no influence on the extend of GLS reduction. Conclusion Low native CMR T1 times, indicating sphingolipid accumulation in the myocardium, seem to represent the beginning of cardiac involvement in FD and might predict the course of GLS. GLS is a sensitive parameter for early detection of cardiac manifestation and disease progression, while LGE and CMR-EF could not recognize slight deterioration of left ventricular function.