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Background and ObjectivesGuidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE).MethodsWe performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations.ResultsBetween May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5–7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28–16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%).DiscussionCardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam Movement Sciences and the Dutch Olympic Committee. Background Cardiac magnetic resonance imaging (CMR) T1 mapping is an established tool for tissue characterisation. This is of particular interest in athletes as differentiation of the ‘grey zone’ between physiological adaptation to sports and pathology can be highly challenging. To correctly interpret individual T1 times, T1 times are conventionally compared to normal values derived from healthy controls. However, whether these values can be applied to elite athletes with different types of cardiac adaptation is unknown. Purpose To determine differences in native T1 times between elite athletes and healthy non-athletic controls and to determine differences in athletes with different types of cardiac remodelling. Methods This is a cross-sectional analysis of elite athletes included in the ELITE cohort. ELITE collects the preparticipation cardiovascular screenings data from all athletes that perform at the highest national, international and/or Olympic level in the Netherlands. All athletes were sixteen years or older. The screening includes cardiovascular magnetic resonance imaging on a Siemens Avanto fit 1.5T machine with cine-imaging, delayed hyperenhancement and a three-pulse shortened modified look-locker inversion recovery 5(3)3 sequence. For this analysis, all athletes with a history of cardiovascular disease or pathological late gadolinium enhancement were excluded. Athletes were classified according to the Mitchell Sports Classification based on the intensity (low (L) / moderate (M) / high (H)) of the dynamic (D) and static components (S). Native- and post-contrast T1 mapping times were calculated by manually tracing the endocardial- and epicardial contours. Results A total of 117 elite athletes (44% women; mean age 26±6.5; Mitchell sports classification: 47 HS/HD, 8 HS/LD, 5 HS/MD, 36 LS/HD, 16 MS/HD, 3 MS/MD, 3 missing) and 48 healthy non-athletic controls (54% women; mean age 39±15.1). Men had lower t1 times compared to women, both in athletes (949ms vs 964ms, p Conclusion Men demonstrate markedly shorter T1 times compared to women in both athletes and controls. Moreover, native T1 times were associated with markers for cardiac remodelling. Sex- and athlete-specific characteristics should be taken into account when interpreting T1 times in athletes.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Amsterdam Movement Sciences (AMS); Dutch National Olympic Committee & National Sports Federation (NOC*NSF); Heart To Handle. Background Differentiating between exercise-induced cardiac remodelling (EICR) and pathology constitutes a central challenge in sports cardiology. To facilitate this differentiation, reference ranges for cardiovascular magnetic resonance imaging (CMR) are needed. However, female athletes, and especially, female elite athletes with potentially the most outspoken adaptation, are severely underrepresented. Moreover, no large studies including CMR data in female, elite athletes are currently available. Purpose To quantify EICR on CMR in a large cohort of female, elite athletes, compared with currently available reference values of the general female, and female athlete population. Methods We performed a cross-sectional CMR analysis in female elite athletes aged ≥16 years, included in the ELITE cohort. We excluded athletes with known cardiovascular disease. The primary outcome was EICR quantification as BSA indexed RV and LV end-diastolic volume (EDVi), LV wall mass (LVMi), LV remodelling index (LVMi/LVEDVi), and LV/RV ratio (LVEDi/RVEDVi). Second, we compared our parameters with reference ranges (1,2). CMR was performed according to a uniform protocol, and included cine-imaging and delayed hyperenhancement, preferentially on 1.5T. A dedicated core-lab analysed all CMRs in Circle Cardiovascular Imaging. Results We included 102 female elite athletes, 97% caucasian, mean age of 26.3 ±5.0, BSA 1.79 ±0.14 m2, and mean professional athlete years of 10.3 ±5. Main athlete disciplines (≥10 hours/week) were field hockey (15%), rowing (13%), road cycling (12%), and European style football (10%). Female elite athletes had marked EICR as compared with general population reference values, with higher LVEDVi (108 ±13.9 vs 69 ±12 ml/m2, p Conclusion EICR on CMR in female, elite athletes is mainly characterised by isolated increased volumes, with a considerable proportion (11%) demonstrating no EICR. Compared with the general population, female athletes have larger cardiac ventricular volumes and wall mass; compared with available elite athlete reference ranges comparable ventricular volumes, but a larger spread in cardiac wall mass. Our results constitute a first step towards sex-specific CMR reference ranges for female athletes.

IntroductionThe cardiovascular benefits of physical exercise are well-known. However, vigorous exercise has also been associated with adverse cardiac effects. To improve our understanding of cardiovascular adaptation to exercise versus maladaptation and pathology, the limits of adaptation should be firmly established using state-of-the-art diagnostic modalities. We therefore initiated the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort to investigate the longitudinal (beneficial and pathological) cardiovascular effects of intensive elite sports and exercise.Methods and analysisELITE is a prospective, multicentre, longitudinal cohort study. Elite athletes, from the age of sixteen, are recruited in The Netherlands. The primary objective is to determine the association between elite sports and exercise-induced cardiac remodelling, cardiac pathology, and health benefits over time. Secondary objectives include determining and identifying genetic profiles of elite athletes, and how these are associated with cardiac indices. ELITE will collect data from consultations, electrocardiography, echocardiography and cardiac magnetic resonance imaging, and training- and injury data. ELITE will also collect blood for biobanking and cardiogenetics. Follow-up will take place at intervals of two to five years, and after the elite athletes’ professional careers have ended. In addition, a subcohort of ELITE has been established to investigate cardiac sequelae following infections associated with myocardial involvement, including SARS-CoV-2. ELITE is a prospective observational study; therefore, analyses will be primarily explorative.Ethics and disseminationThis study has been approved by the Medical Ethics Review Board of the Amsterdam University Medical Centers (NL71682.018.19). The results of the study will be disseminated by publication in peer-reviewed journals (Netherlands Trial Register number: NL9328).

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: Guidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardio-aortic sources of embolism than transthoracic echocardiography (TTE). Methods: We performed a prospective, single center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent routine stroke work-up, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardio-aortic source of embolism on cardiac CT versus TTE in patients undergoing both investigations. Results: Between May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5–7) minutes with poor scan quality in only 3%. In total, 350/452 (77.4%) patients underwent TTE, 99 of which were performed in an outpatient setting. Reasons for not undergoing TTE were: death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardio-aortic source of embolism was detected in 40/350 (11.4%) patients on CT, compared to 17/350 (4.9%) on TTE (odds ratio 5.60, 95%CI: 2.28–16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 54/452 (12.2%). Among 175 patients with cryptogenic stroke after routine work-up, cardiac CT identified a cause of the stroke in 11 (6.3%). Discussion Cardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared to TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

Rationale About one-third of ischaemic strokes are caused by cardioembolism, and a substantial proportion of cryptogenic strokes likely also originate from the heart or aortic arch. Early determination of aetiology is important to optimise management. Computed Tomography-angiography of the heart is emerging as an alternative to echocardiography to detect cardio-aortic sources of embolism in stroke patients, but its diagnostic yield in acute ischaemic stroke has not been thoroughly assessed. Hypothesis: We hypothesise that electrocardiography-gated computed tomography-angiography of the heart and aortic arch, acquired in the acute phase in patients with ischaemic stroke, has a higher diagnostic yield than transthoracic echocardiography as a first-line screening method for detection of cardio-aortic sources of embolism. Methods and design Mind the Heart is a single-centre prospective observational cohort study. We will include consecutive adult patients with acute ischaemic stroke who are potentially eligible for reperfusion therapy. Patients undergo non-electrocardiography-gated computed tomography-angiography of the aortic arch, cervical and intracranial arteries, directly followed by prospective sequential electrocardiography-gated cardiac computed tomography-angiography. Routine work-up for cardioembolism including 12-leads electrocardiography, Holter electrocardiography and transthoracic echocardiography is performed as soon as possible. The primary endpoint is the proportion of patients with a predefined high-risk cardio-aortic source of embolism on computed tomography-angiography versus transthoracic echocardiography in patients who underwent both investigations. Based on an expected 5% additional yield of computed tomography-angiography, a sample size of 450 patients is required. Conclusions The Mind the Heart study will generate a reliable estimate of the diagnostic yield of echocardiography-gated cardio-aortic computed tomography-angiography performed in the acute phase of ischaemic stroke.

Funding Acknowledgements Type of funding sources: None. Background Late gadolinium enhancement (LGE) demonstrates regional differences in myocardial extracellular volume, such as seen in myocardial fibrosis, and is associated with diverse cardiac diseases and is a predictive factor for sudden cardiac death. Earlier findings suggest an LGE prevalence of 7% in endurance athletes of varying age and exercise exposure. However, findings for (potentially benign) LGE indices in athletes performing at elite-level are lacking. Purpose To establish a specific baseline for LGE findings on CMR in apparently healthy, elite-level athletes. Methods We performed a cross-sectional assessment of hinge point late gadolinium enhancement (HP-LGE) in elite athletes (national-, international-, Olympic-, Paralympic-level or comparable). All athletes were asymptomatic and examined during pre-participation cardiovascular screening. Each underwent CMR using 3 Tesla- (Philips) or 1½ Tesla- (Siemens) MRI-scanners including short-axis cine imaging, LGE, and T1-mapping. CMR data were analysed using cvi42, statistical analyses using R. Athletes with HP-LGE were compared to athletes without HP-LGE. Results We screened 210 athletes, 34% female, with a mean age (±SD) of 28±7 and body surface area (BSA) of 2.0±0.2 m2 participating in road cycling (n=38), field hockey (n=28), water polo (n=27), soccer (n=21), rowing (n=18), swimming (n=13), track cycling (n=12), tennis (n=10), sailing (n=10), para-cycling (n=7), and miscellaneous (n=26) sports. We observed indexed end-diastolic volumes (EDVi) of 119±20 and 123±20 ml/m2, stroke volumes 131±33 and 127±37 ml, and ejection fractions of 56±5 and 54±6 %, in the left- (LV) and right ventricle (RV), respectively. Eighty-four (40%) athletes had HP-LGE. Proportionally, fewer female athletes had HP-LGE as compared with men (24 vs 41 %, p=0.014). Athletes with HP-LGE had greater LV- and RV EDVi (123±20 and 127±20 ml/m2 vs. 117±19 and 120±19 ml/m2, p=0.02 and p=0.01; for LV and RV, respectively), lower RV ejection fractions (53±5 vs. 55±6, p-value 0.04), smaller estimated global extra cellular volumes of the LV (24 vs 25 %, p=0.01). There were no differences in indexed LV- and RV end-systolic volumes, LV- and RV stroke volumes, LV ejection fraction and indexed wall mass, global native-, or contrast-enhanced T1 times in athletes with and without HP-LGE. Conclusion Late gadolinium enhancement in the hinge point is present in 40% of asymptomatic elite athletes. Athletes with HP-LGE were more frequently men, had higher LV- and RV EDVi, suggesting an association with ventricular volumes. Our findings in asymptomatic, elite athletes, with normal ventricular function and T1 times, suggest that HP-LGE could be a sign of physiological sports adaptation instead of an early sign of pathology. Further studies are warranted to investigate if HP-LGE is associated with long-term cardiac changes or the development of cardiac pathology.