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Background/Introduction Specific athlete reference values for cardiac volumes and function using cardiac magnetic resonance (CMR) parameters have been reported and are used in clinical practice. Elite athletes are conventionally thought to demonstrate the highest levels of physiological adaptation to sports and therefore dictate the upper limit of normal for biventricular size and function in the athlete population. Purpose To compare volumetric parameters in a cohort of both male and female elite-level athletes to previously published reference values. Methods We used data from the prospective ELITE-cohort, which collects pre-participation data of elite athletes (national-, international-, Olympic-, Paralympic-level), including CMR imaging. Athletes suspected of pathology based on comprehensively investigated electrocardiograph, exercise test, echocardiogram and late gadolinium enhancement were excluded. Biventricular volumes were derived from short-axis cine images using Cvi42 (v5.1.2.) and indexed for body surface area (BSA). Volumetric parameters were compared to the previously reported gender- and Mitchell sports classification specific cardiac 95th percentile (95%tile) reference values, as reported by Luijkx et al.: left-ventricle (LV) end-diastolic volume (EDV) / BSA for high-static and high-dynamic sports (HS/HD; ♀ 142 ♂ 158); low-static and high-dynamic (LS/HD; ♀ 127 ♂ 149); high-static and low-dynamic (HS/LD; ♀ 114 ♂ 140); right ventricle (RV) EDV / BSA HS/HD (♀ 154 ♂ 184), LS/HD (♀ 136 ♂ 163), and HS/LD (♀ 120 ♂ 157). Results We analysed a total of 221 athletes (38% female), with a median age (IQR) of 26.0 (22.5–29.8) years, and mean ±SD BSA of 1.96±0.22 m2. Athletes were classified according to the Mitchell sports classification: HS/HD 116 (54%); LS/HD 61 (29%); moderate-static and high-dynamic (MS/HD) 20 (9.4%); HS/LD 16 (7.5%) (Table). We found smaller mean ±SD (95%tile) RV EDV/BSA in athletes participating in HS/HD sports (♀: 117±20 (148) and ♂: 133±20 (160)) and LS/HD sports (♀: 109±11 (129) and ♂: 119±15 (142)) and smaller LV EDV/BSA in male athletes in LS/HD sports (116±15 (138)) compared to reference values, (Figure). When using conventional cut-offs in our population we found 10 (4.5%) and 2 (0.9%) athletes above 95%tile for LVEDV/BSA and RVEDV/BSA, respectively (Figure). Conclusion In a cohort consisting of healthy, elite athletes, volumetric adaptations were less outspoken as compared with current reference ranges, specifically in the RV. Only 1 percent of our athletes exceeded conventional 95%tile references for the RV. Potentially, current athlete reference values could overestimate healthy upper limits of cardiac volumes in elite athletes. Our study could indicate that a stricter definition of volumetric reference values, including 95%tile, might be of added value in the specific group of elite athletes to help differentiate between pathology and sports adaptation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Amsterdam Movement Sciences (P1A210AMC2018)

Background/Introduction In the general population, cardiac magnetic resonance imaging (CMR) T1 mapping is an established tool used for cardiac tissue characterisation. Such characterisation is of particular interest in athletes, as differentiation of the “grey zone” between physiological adaptation to sports and myocardial pathology can be highly challenging. To correctly interpret individual T1 times, T1 times are conventionally compared with normal values derived from healthy controls. However, whether these normative T1 values can be applied to elite athletes, who commonly demonstrate the most extreme cardiac adaptation, is unknown. Purpose To determine whether there are gender-specific differences in normative T1 times between elite athletes and healthy controls. Methods This study is a cross-sectional assessment of healthy athletes included the ELITE-cohort. ELITE includes athletes at national, international, and Olympic level in the Netherlands, aged sixteen years or older and without a history of cardiovascular disease. All athletes undergo standard periodic preparticipation screening with cardiovascular magnetic resonance imaging (Phillips 1.5 Tesla), including native T1 mapping. For the current study, we compared athletes to healthy controls per gender group. T1 inversion times were calculated in Circle Cardiovascular software (v5.12); means for global and segmented myocardium, according to the AHA 16-segment model, were determined using R (v4.1.4). Results A total of 81 elite athletes (35 women, 43.2%) with a median (IQR) age of 26 (22.0–29.55) years and 55 healthy controls (27 women, 49.1%), with a mean age of 38.4±15 years were included (Table 1). Overall, mean global T1 times were markedly shorter in athletes compared with controls (959±21.1ms vs. 984±26.6ms, P Conclusion(s) Athletes demonstrate markedly shorter T1 times as compared with healthy controls, both in women and men. Sex-specific, athlete-normative T1 times should be taken into account when interpreting T1 times in athletes undergoing cardiac evaluation. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam Movement Sciences and the Dutch Olympic Committee*Dutch Sports Federation

Background/Introduction SARS-CoV-2 (subclinical) myocarditis has been demonstrated in up to 5% in athletes, and is currently a topic being intensively investigated. However, more subtle changes in function and volumetric parameters have been less well documented, especially in elite athletes, who perform at the highest levels of sports, with potentially the most outspoken adaptation. Purpose To determine differences in cardiac function and volumetric parameters using cardiac magnetic resonance imaging (CMR) in elite athletes recovered from a SARS-CoV-2 infection as compared to non-infected elite athletes (controls). Methods We included elite athletes from the ELITE (Evaluation of Lifetime Intensive Top-level sports and Exercise) cohort, who voluntary undergo cardiovascular pre-participation screenings, which includes cardiac magnetic resonance imaging (CMR). SARS-CoV-2 infection was diagnosed with a positive-PCR or antibody test (if unvaccinated). The primary outcome was the incidence of structural cardiac changes on CMR, defined as LV/RV BSA indexed-EDV (EDVi), LV/RV BSA indexed-ESV (ESVi), LV/RV EF, presence of pathological late gadolinium enhancement (LGE) (excluding hinge point fibrosis), and T1 times. Results We included 234 elite athletes, mean age 27 (±7), 39% female, with main athletic disciplines (≥10 hours/week) of cycling (24%), field hockey (13%), and water polo (12%). In total 69 elite athletes had documented SARS-CoV-2 infection, and 165 were documented as not exposed to SARS-CoV-2. The majority reported mild symptoms 61/69 (88%), 1/69 (1%) severe symptoms, and 7/69 (11%) no symptoms. Mean time between infection and CMR was 2.8 (±2) months. CMR showed no significant difference between elite athletes with SARS-CoV-2 and without (Table) in mean LVEDVi (117±19 vs 120±19 ml/m2, p=0.29), LVESVi (50.6±11 vs 53.2±11 ml/m2, p=0.12), LVEF (56.9% ±5 vs 55.8% ±5, p=0.14), RVEDVi (120±20 vs 122±19 ml/m2, p=0.56), RVESVi (54.5±11 vs 56.2±11 ml/m2, p=0.29), and RVEF (54.6% ±4 vs 53.9% ±5, p=0.23). In 4/69 (4.7%) vs 1/165 (1.3%) pathological non-ischemic pattern of myocardial LGE was present (≤20% of total LV mass), of which one athlete (1.2%) showed increased T1 time, all with no deterioration in right and left ventricle function and volumetric parameters (Figure) after SARS-CoV-2 infection. All athletes made a full recovery and returned to elite competitive sports. Conclusion(s) This cross-sectional study of elite athletes demonstrates that infection with SARS-CoV-2 is not associated with deterioration in cardiac function and volumetric parameters on CMR compared with non-infected athletes, also in the small subset of athletes with pathological LGE patterns after SARS-CoV-2 infection. Prospective studies with long-term follow-up are needed to establish whether intensive sports is associated with long-term cardiac deleterious effects in elite athletes exposed to SARS-CoV-2. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Dutch Heart FoundationDutch National Olympic Committee & National Sports Federation (NOC*NSF)

Background/Introduction Multidisciplinary teams (MDT) are an integral part of cardiology. In sports cardiology wide area of expertise is required to differentiate between extraordinary pathophysiological adaption and pathology. In Addition, expertise-based sports advice should be prescribed with great care considering the great impact on (professional) sports careers. Specific guidelines for the composition of MDT's for sports cardiology are currently lacking. We established a sports cardiology MDT in April 2020 (Amsterdam UMC), consisting of experts in the fields of sports medicine, cardiogenetics and paediatric cardiology, cardiovascular imaging and electrophysiology, with bi-monthly meetings. Cases were contributed from cardiologists or referred nationally for expertise with patients/athletes varying from recreational to elite-level sports. Purpose To describe our infrastructure and utilization of a sports cardiology MDT, and to justify the need for a sports cardiology MDT. Methods We retrospectively analysed all MDT reviewed cases (from April 2020 to April 2021), and collected follow-up data 1 year after initial MDT review. Data were classified according to type/level of sports. We compared diagnosis and/or reason for referral and sports advice at initial MDT application and after panel review. In addition we abstracted data on occurrence of cardiac symptoms and/or cardiac events, and adherence to sports advice. Results 112 cases underwent MDT review, with a mean age of 32 (SD 16.0) years. In total 12% were women, 38% professional athletes, and 30% engaged in high dynamic/low static sports. Reasons for referral were personalised sports advice in 48%, expert opinion in 28%, and abnormal ECG/CMR/CPX in 24%. The diagnosis was revised in 55% (n=61), main groups; 1) suspicion of (non-specified) cardiomyopathy (CMP) to no cardiac pathology in 20% (n=12), and 2) “cardiac abnormalities with no clear diagnosis” to “no cardiac pathology” in 36% (n=22) (Figure 1). Sports advice was revised to more personalized sports advice in 30% (n=34) (Figure 2), main groups; no restriction to no peak load/specific maximum load in 38% (n=13), and no restrictions to no competitive sports in 26% (n=9). At 1 year follow-up, the (sports) advice was adhered in 99,98% (n=111), and cases with no sports restrictions reported no cardiac symptoms in 99% (n=72/73), and no major acute cardiovascular events in 100% (73/73). No further revisions of diagnoses were found to have taken place. Conclusion Our experience with a comprehensive, sports cardiology MDT demonstrates that such an approach is feasible, and leads to more personalised treatment- and sports advice in athletes. Medium-term adherence to sports advice given is high. A team-based approach also leads to a higher percentage definitive diagnoses. Our findings serve as a proof-of-concept of the added value of the sports cardiology team in care for athletes and patients who wish to engage in sports and exercise. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Dutch Olympic Committee*Dutch Sports Federation (NOC*NSF)Amsterdam Movement Sciences (AMS) Figure 1. Revised diagnosis before and after panel review (N=61)Figure 2. Revised sports advice before and after panel review (N=34)

Background The growing availability of mobile phones increases the popularity of portable telemonitoring devices. An atrial fibrillation diagnosis can be reached with a recording of 30s on such telemonitoring devices. However, current commercially available automatic algorithms still require approval by experts. Purpose In this research we aimed to build an artificial intelligence (AI) algorithm to improve automatic distinction of atrial fibrillation (AF) from sinus rhythm (SR), to ultimately save time, costs, and to facilitate telemonitoring programs. Methods We developed a deep convolutional neural network (CNN), based on a residual neural network (ResNet), tailored to single-lead ECG analysis. The CNN was trained using publicly available single-lead ECGs from the 2017 PhysioNet/ Computing in Cardiology Challenge. This dataset consists of 60% SR, 9% AF, 30% alternative rhythm, and 1% noise ECGs. The 8528 available ECGs were divided into a training (90%) and validation set (10%) for model development and hyperparameter optimization. Results The trained CNN was applied to an independent set containing single-lead ECGs of 600 patients equally divided into two groups: SR and AF. Both groups comprised of 300 unique ECGs (SR; 60% male, 63±11 years, AF; 38% male, 56±14 years). In distinguishing between AF and SR, the method achieved an accuracy of 0.92, an F1-score of 0.91, and area under the ROC-curve of 0.98. Conclusion The results demonstrate that distinguishing SR and AF by a fully automatic AI algorithm is feasible. This approach has the potential to reduce cost by minimizing expert supervision, especially when extending the algorithm to other heart rhythms, like premature atrial/ventricular contractions and atrial flutter. Figure 1. ROC curve Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dekkerbeurs - Hartstichting

Peptides produced by the renin-angiotensin system play a major role in the development and progression of various cardiovascular diseases. One of these peptides, angiotensin II, is a potent vasoconstrictor that exerts most of its effects through the human AT1 receptor. Following the discovery of a functional variation in the angiotensin-converting enzyme gene, research has identified other genetic variations in the renin-angiotensin system that may contribute to cardiovascular disorders. Of the described polymorphisms in the AT1-receptor gene, the A1166C transversion is associated with human essential hypertension. We have used the TGR(alpha MHC-h AT1) rat model, which overexpresses the human AT1 receptor in the myocardium, to study some of the associations between an increased AT1-receptor number and cardiovascular disorders. Our results suggest that under physiological conditions overexpression of the AT1 receptor causes no changes in cardiovascular structure; however, pressure and volume overload lead to hypertrophic growth in this model. While the AT1-receptor polymorphism may not cause cardiovascular disorders directly, it can perhaps contribute to a process that is started by other factors, such as increased activity or uptake by tissues of plasma renin, which leads to local activation of the renin-angiotensin system. Our data indicate that the AT1-receptor polymorphism is probably associated with an increased responsiveness to angiotensin II. Under basal conditions, this increased responsiveness does not seem to affect the heart, but it may exert adverse effects under loading or high-renin conditions.

We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletion polymorphism may be related to arterial phenotypic differences that could explain the adverse effects of deletion polymorphism. Accordingly, contractile responses to angiotensin I and II (0.1 nmol.1(-1)-1 micromol.1(-1), endothelium-dependent relaxation to methacholine (0.01-100 micromol.1(-1), and the effect of NG-monomethyl-L-arginine (L-NMMA; 100 micromol.1(-1) on phenylephrine (10 micromol.1(-1) induced contraction, were studied in isolated rings of internal mammary arteries obtained from patients undergoing coronary bypass surgery. The results were analysed according to the ACE genotype of the patient (II, n = 8; ID, n = 11; DD, n = 9) as well as the presence/absence of either allele. The arteries from patients with the D allele (ID/DD) displayed a lower sensitivity to methacholine (P0.05 vs II), which suggested that the capacity of the endothelium for nitric oxide release in response to stimulation was also lower. By contrast, the increase in phenylephrine-induced contraction, by pre-incubation with L-NMMA, was more pronounced in the group with the DD allele (31 +/- 5%) than with the ID (11 +/- 11%) and II alleles (1 +/- 11%, P0.05 vs DD), which suggested a higher level of basal nitric oxide release. Finally, the differences in the responses to angiotensin I and II, which were used to evaluate the vascular conversion of angiotensin I, indicated that the level of angiotensin I conversion was higher in patients with the D allele (ID/DD, P0.05 vs II). The findings of this study indicate that ACE insertion/deletion polymorphism is related to arterial phenotypic differences in endothelial function and angiotensin I conversion.