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Background: Achievement of guideline-recommended levels of physical activity (≥150 minutes of moderate-to-vigorous physical activity per week) is associated with lower risk of adverse cardiovascular events and represents an important public health priority. Although physical activity commonly follows a "weekend warrior" pattern, in which most moderate-to-vigorous physical activity is concentrated in 1 or 2 days rather than spread more evenly across the week (regular), the effects of physical activity pattern across a range of incident diseases, including cardiometabolic conditions, are unknown., Methods: We tested associations between physical activity pattern and incidence of 678 conditions in 89 573 participants (62±8 years of age; 56% women) of the UK Biobank prospective cohort study who wore an accelerometer for 1 week between June 2013 and December 2015. Models were adjusted for multiple baseline clinical factors, and P value thresholds were corrected for multiplicity., Results: When compared to inactive (<150 minutes moderate-to-vigorous physical activity/week), both weekend warrior (267 total associations; 264 [99%] with lower disease risk; hazard ratio [HR] range, 0.35-0.89) and regular activity (209 associations; 205 [98%] with lower disease risk; HR range, 0.41-0.88) were broadly associated with lower risk of incident disease. The strongest associations were observed for cardiometabolic conditions such as incident hypertension (weekend warrior: HR, 0.77 [95% CI, 0.73-0.80]; P =1.2×10 -27 ; regular: HR, 0.72 [95% CI, 0.68-0.77]; P =4.5×10 -28 ), diabetes (weekend warrior: HR, 0.57 [95% CI, 0.51-0.62]; P =3.9×10 -32 ; regular: HR, 0.54 [95% CI, 0.48-0.60]; P =8.7×10 -26 ), obesity (weekend warrior: HR, 0.55 [95% CI, 0.50-0.60]; P =2.4×10 -43 , regular: HR, 0.44 [95% CI, 0.40-0.50]; P =9.6×10 -47 ), and sleep apnea (weekend warrior: HR, 0.57 [95% CI, 0.48-0.69]; P =1.6×10 -9 ; regular: HR, 0.49 [95% CI, 0.39-0.62]; P =7.4×10 -10 ). When weekend warrior and regular activity were compared directly, there were no conditions for which effects differed significantly. Observations were similar when activity was thresholded at the sample median (≥230.4 minutes of moderate-to-vigorous physical activity/week)., Conclusions: Achievement of measured physical activity volumes consistent with guideline recommendations is associated with lower risk for >200 diseases, with prominent effects on cardiometabolic conditions. Associations appear similar whether physical activity follows a weekend warrior pattern or is spread more evenly throughout the week., Competing Interests: P.T.E. receives sponsored research support from Bayer AG, Bristol Myers Squibb, Pfizer, and Novo Nordisk; he has also served on advisory boards or consulted for Bayer AG. S.A.L. is an employee of Novartis as of July 2022. S.A.L. received sponsored research support from Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, Fitbit, Medtronic, Premier, and IBM, and has consulted for Bristol Myers Squibb, Pfizer, Blackstone Life Sciences, and Invitae. The other authors report no conflicts.

Background: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood., Objectives: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression., Methods: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygA C ). CVD events were ascertained from electronic health records., Results: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygA C (standardized β: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygA C reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023)., Conclusions: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression., Competing Interests: Funding Support and Author Disclosures This study is in part funded by National Institutes of Health (NIH) grants R56AR077187-01 and P01HL131478-05. This study was in part supported by NIH grants 1R01AR077187 (Dr Tawakol), P01HL131478 (Drs Tawakol and Fayad), K23HL151909 (Dr Osborne). Dr Osborne has received consulting fees from WCG Intrinsic Imaging, LLC, for unrelated work. Dr Choi has received support in part by funding from the National Institute of Mental Health (K08MH127413) and a NARSAD Brain and Behavior Foundation Young Investigator Award. Dr Smoller has received support for work outside the submitted research; is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity); has received an honorarium for an internal seminar at Tempus Labs and Biogen, Inc; and is PI of a study sponsored by 23andMe. Dr Tawakol has received grants from the National Institutes of Health, International Atomic Energy Agency, Osler/Harvard, and Lung Biotechnologies for work outside the submitted research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest None.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort., (© 2024 European Society of Cardiology.)

Preparticipation cardiovascular screening (PPCS) in young athletes is performed to detect conditions associated with sudden cardiac death. Many medical societies and sports governing bodies support the addition of a 12-lead electrocardiogram (ECG) to the history and physical to improve PPCS sensitivity. The current standard for ECG interpretation in athletes, the International Criteria, was developed to distinguish physiologic from pathologic ECG findings in athletes. Although application of the International Criteria has reduced the PPCS false-positive rate, interpretative challenges and potential areas of improvement remain. This review provides an overview of common pitfalls and future directions for ECG interpretation in athletes., Competing Interests: Disclosure The authors report no disclosures. Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) is difficult to phenotype. The metrics of severity are frequently discordant, making prognostication challenging. Flow state is central to accurately determining severity. We sought to evaluate the prognostic value of dimensionless index (DI) and transvalvular flow rate (Q) in AS. We evaluated 2 independent, longitudinal registries of ≥ moderate severity AS (aortic valve area ≤1.5 cm 2 or mean gradient ≥20 mm Hg) with complete data follow-up. In the primary cohort (n = 1,104, 77 ± 11 years, 40% female), the DI and Q category significantly predicted mortality (p <0.001) (Figure 1), with the highest risk being low DI and low Q (DI <0.25, Q ≤210 mL/s). In the validation cohort (n = 939, 70 ± 13 years, 42% female), similar results were seen in Kaplan-Meier (p <0.001) and multivariable Cox model analyses (p <0.01). We advocate for wider combined use of DI and Q in AS assessment to augment current diagnostic and prognostic approaches., Competing Interests: Declaration of competing interest Dr. Namasivayam has received the Nvidia Corporation Academic Hardware Grant. Dr. Pibarot has received funding from Edwards Lifesciences and Medtronic for echo corelab or in vitro analyses with no personal compensation. The remaining authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To leverage deep learning on the resting 12-lead electrocardiogram (ECG) to estimate peak oxygen consumption (V˙O2peak) without cardiopulmonary exercise testing (CPET)., Methods and Results: V ˙ O 2 peak estimation models were developed in 1891 individuals undergoing CPET at Massachusetts General Hospital (age 45 ± 19 years, 38% female) and validated in a separate test set (MGH Test, n = 448) and external sample (BWH Test, n = 1076). Three penalized linear models were compared: (i) age, sex, and body mass index ('Basic'), (ii) Basic plus standard ECG measurements ('Basic + ECG Parameters'), and (iii) basic plus 320 deep learning-derived ECG variables instead of ECG measurements ('Deep ECG-V˙O2'). Associations between estimated V˙O2peak and incident disease were assessed using proportional hazards models within 84 718 primary care patients without CPET. Inference ECGs preceded CPET by 7 days (median, interquartile range 27-0 days). Among models, Deep ECG-V˙O2 was most accurate in MGH Test [r = 0.845, 95% confidence interval (CI) 0.817-0.870; mean absolute error (MAE) 5.84, 95% CI 5.39-6.29] and BWH Test (r = 0.552, 95% CI 0.509-0.592, MAE 6.49, 95% CI 6.21-6.67). Deep ECG-V˙O2 also outperformed the Wasserman, Jones, and FRIEND reference equations (P < 0.01 for comparisons of correlation). Performance was higher in BWH Test when individuals with heart failure (HF) were excluded (r = 0.628, 95% CI 0.567-0.682; MAE 5.97, 95% CI 5.57-6.37). Deep ECG-V˙O2 estimated V˙O2peak <14 mL/kg/min was associated with increased risks of incident atrial fibrillation [hazard ratio 1.36 (95% CI 1.21-1.54)], myocardial infarction [1.21 (1.02-1.45)], HF [1.67 (1.49-1.88)], and death [1.84 (1.68-2.03)]., Conclusion: Deep learning-enabled analysis of the resting 12-lead ECG can estimate exercise capacity (V˙O2peak) at scale to enable efficient cardiovascular risk stratification., Competing Interests: Conflict of interest: B.M.W. has consulted for Change Healthcare. P.D.A. and P.B. are supported by grants from Bayer AG and IBM applying machine learning in cardiovascular disease. P.B. serves as a consultant for Novartis and Prometheus Biosciences. P.T.E. receives sponsored research support from Bayer AG and IBM Research; he has also served on advisory boards or consulted for Bayer AG, MyoKardia, and Novartis. S.A.L. receives sponsored research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, and IBM, and has consulted for Bristol Myers Squibb/Pfizer, Bayer AG, and Blackstone Life Sciences. S.A.L. is now an employee of Novartis Institute for Biomedical Research. The remaining authors have no disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: None declared.

Background: Understanding the incidence, causes, and trends of sudden cardiac death (SCD) among young competitive athletes is critical to inform preventive policies., Methods: This study included National Collegiate Athletic Association athlete deaths during a 20-year time frame (July 1, 2002, through June 30, 2022). Athlete deaths were identified through 4 separate independent databases and search strategies (National Collegiate Athletic Association resolutions list, Parent Heart Watch database and media reports, National Center for Catastrophic Sports Injury Research database, and insurance claims). Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD., Results: A total of 143 SCD cases in National Collegiate Athletic Association athletes were identified from 1102 total deaths. The National Collegiate Athletic Association resolutions list identified 117 of 143 (82%), the Parent Heart Watch database or media reports identified 89 of 143 (62%), the National Center for Catastrophic Sports Injury Research database identified 63 of 143 (44%), and insurance claims identified 27 of 143 (19%) SCD cases. The overall incidence of SCD was 1:63 682 athlete-years (95% CI, 1:54 065-1:75 010). Incidence was higher in male athletes than in female athletes (1:43 348 [95% CI, 1:36 228-1:51 867] versus 1:164 504 [95% CI, 1:110 552-1:244 787] athlete-years, respectively) and Black athletes compared with White athletes (1:26 704 [1:20 417-1:34 925] versus 1:74 581 [1:60 247-1:92 326] athlete-years, respectively). The highest incidence of SCD was among Division I male basketball players (1:8188 [White, 1:5848; Black, 1:7696 athlete-years]). The incidence rate for SCD decreased over the study period (5-year incidence rate ratio, 0.71 [95% CI, 0.61-0.82]), whereas the rate of noncardiovascular deaths remained stable (5-year incidence rate ratio, 0.98 [95% CI, 0.94-1.04]). Autopsy-negative sudden unexplained death (19.5%) was the most common postmortem examination finding, followed by idiopathic left ventricular hypertrophy or possible cardiomyopathy (16.9%) and hypertrophic cardiomyopathy (12.7%), in cases with enough information for adjudication (118 of 143). Eight cases of death were attributable to myocarditis over the study period (1 case from January 1, 2020, through June 30, 2022), with none attributed to COVID-19 infection. SCD events were exertional in 50% of cases. Exertional SCD was more common among those with coronary artery anomalies (100%) and arrhythmogenic cardiomyopathy (83%)., Conclusions: The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD., Competing Interests: Disclosures Dr Ackerman is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, Thryv Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, and Pfizer. None of these entities was involved in this study. Dr Baggish has received funding from the National Institute of Health/National Heart, Lung, and Blood Institute, the National Football Players Association, the American Heart Association, and the American Medical Society for Sports Medicine to study cardiovascular outcomes among elite athletes and receives compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, and US Rowing. Dr Drezner has received funding from the American Medical Society for Sports Medicine, the American Heart Association, and the National Center for Catastrophic Sports Injury Research. Dr Harmon has received funding from the American Medical Society for Sports Medicine, Football Research, Inc, the Pac-12, and the American Heart Association. Dr Kucera is supported by funds from the National Center for Catastrophic Sports Injury Research.

Background: Imaging evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging. Myocardial strain assessment by echocardiography is an increasingly utilized technique for detecting subclinical left ventricular (LV) and right ventricular (RV) dysfunction. We aimed to evaluate the diagnostic and prognostic utility of LV and RV strain in ARVC., Methods: Patients with suspected ARVC (n = 109) from a multicenter registry were clinically phenotyped using the 2010 ARVC Revised Task Force Criteria and underwent baseline strain echocardiography. Diagnostic performance of LV and RV strain was evaluated using the area under the receiver operating characteristic curve analysis against the 2010 ARVC Revised Task Force Criteria, and the prognostic value was assessed using the Kaplan-Meier analysis., Results: Mean age was 45.3±14.7 years, and 48% of patients were female. Estimation of RV strain was feasible in 99/109 (91%), and LV strain was feasible in 85/109 (78%) patients. ARVC prevalence by 2010 ARVC Revised Task Force Criteria is 91/109 (83%) and 83/99 (84%) in those with RV strain measurements. RV global longitudinal strain and RV free wall strain had diagnostic area under the receiver operating characteristic curve of 0.76 and 0.77, respectively (both P <0.001; difference NS). Abnormal RV global longitudinal strain phenotype (RV global longitudinal strain > -17.9%) and RV free wall strain phenotype (RV free wall strain > -21.2%) were identified in 41/69 (59%) and 56/69 (81%) of subjects, respectively, who were not identified by conventional echocardiographic criteria but still met the overall 2010 ARVC Revised Task Force Criteria for ARVC. LV global longitudinal strain did not add diagnostic value but was prognostic for composite end points of death, heart transplantation, or ventricular arrhythmia (log-rank P =0.04)., Conclusions: In a prospective, multicenter registry of ARVC, RV strain assessment added diagnostic value to current echocardiographic criteria by identifying patients who are missed by current echocardiographic criteria yet still fulfill the diagnosis of ARVC. LV strain, by contrast, did not add incremental diagnostic value but was prognostic for identification of high-risk patients., Competing Interests: Disclosures Dr Namasivayam received support from the Nvidia Corporation Academic Hardware Grant for work unrelated to this article. The other authors report no conflicts.

Objective: Concerns for cardiac involvement after SARS-CoV-2 infection led to widespread cardiac testing in athletes. We examined incidental non-COVID-19 cardiovascular pathology in college athletes undergoing postinfection return-to-play screening., Methods: The Outcomes Registry for Cardiac Conditions in Athletes was a nationwide prospective multicentre observational cohort study that captured testing and outcomes data from 45 institutions (September 2020-June 2021). Athletes with an ECG and transthoracic echocardiogram (TTE) and no pre-existing conditions were included. Findings were defined as major (associated with sudden cardiac death or requiring intervention), minor (warrants surveillance), incidental (no follow-up needed) or uncertain significance (abnormal with subsequent normal testing)., Results: Athletes with both ECG and TTE (n=2900, mean age 20±1, 32% female, 27% black) were included. 35 (1.2%) had ECG abnormalities. Of these, 2 (5.7%) had TTE abnormalities indicating cardiomyopathy (hypertrophic-1, dilated-1), and 1 with normal TTE had atrial fibrillation. Of 2865 (98.8%) athletes with a normal ECG, 54 (1.9%) had TTE abnormalities: 3 (5.6%) with aortic root dilatation ≥40 mm, 15 (27.8%) with minor abnormalities, 25 (46.3%) with incidental findings and 11 (20.4%) with findings of uncertain significance. Overall, 6 (0.2%) athletes had major conditions; however, coronary anatomy and aortic dimensions were inconsistently reported and pathology may have been missed., Conclusion: Major non-COVID-19 cardiovascular pathology was identified in 1/500 college athletes undergoing return-to-play screening. In athletes without ECG abnormalities, TTE's added value was limited to pathological aortic root dilatation in 1/1000 athletes and minor abnormalities warranting surveillance in 1/160 athletes. Two-thirds of findings were incidental or of uncertain significance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of consumer wearable devices (CWDs) to track health and fitness has rapidly expanded over recent years because of advances in technology. The general population now has the capability to continuously track vital signs, exercise output, and advanced health metrics. Although understanding of basic health metrics may be intuitive (eg, peak heart rate), more complex metrics are derived from proprietary algorithms, differ among device manufacturers, and may not historically be common in clinical practice (eg, peak V˙O 2 , exercise recovery scores). With the massive expansion of data collected at an individual patient level, careful interpretation is imperative. In this review, we critically analyze common health metrics provided by CWDs, describe common pitfalls in CWD interpretation, provide recommendations for the interpretation of abnormal results, present the utility of CWDs in exercise prescription, examine health disparities and inequities in CWD use and development, and present future directions for research and development., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Guidelines recommend 150 minutes or more of moderate to vigorous physical activity (MVPA) per week for overall health benefit, but the relative effects of concentrated vs more evenly distributed activity are unclear., Objective: To examine associations between an accelerometer-derived "weekend warrior" pattern (ie, most MVPA achieved over 1-2 days) vs MVPA spread more evenly with risk of incident cardiovascular events., Design, Setting, and Participants: Retrospective analysis of UK Biobank cohort study participants providing a full week of accelerometer-based physical activity data between June 8, 2013, and December 30, 2015., Exposures: Three MVPA patterns were compared: active weekend warrior (active WW, ≥150 minutes with ≥50% of total MVPA achieved in 1-2 days), active regular (≥150 minutes and not meeting active WW status), and inactive (<150 minutes). The same patterns were assessed using the sample median threshold of 230.4 minutes or more of MVPA per week., Main Outcomes and Measures: Associations between activity pattern and incident atrial fibrillation, myocardial infarction, heart failure, and stroke were assessed using Cox proportional hazards regression, adjusted for age, sex, racial and ethnic background, tobacco use, alcohol intake, Townsend Deprivation Index, employment status, self-reported health, and diet quality., Results: A total of 89 573 individuals (mean [SD] age, 62 [7.8] years; 56% women) who underwent accelerometry were included. When stratified at the threshold of 150 minutes or more of MVPA per week, a total of 37 872 were in the active WW group (42.2%), 21 473 were in the active regular group (24.0%), and 30 228 were in the inactive group (33.7%). In multivariable-adjusted models, both activity patterns were associated with similarly lower risks of incident atrial fibrillation (active WW: hazard ratio [HR], 0.78 [95% CI, 0.74-0.83]; active regular: 0.81 [95% CI, 0.74-0.88; inactive: HR, 1.00 [95% CI, 0.94-1.07]), myocardial infarction (active WW: 0.73 [95% CI, 0.67-0.80]; active regular: 0.65 [95% CI, 0.57-0.74]; and inactive: 1.00 [95% CI, 0.91-1.10]), heart failure (active WW: 0.62 [95% CI, 0.56-0.68]; active regular: 0.64 [95% CI, 0.56-0.73]; and inactive: 1.00 [95% CI, 0.92-1.09]), and stroke (active WW: 0.79 [95% CI, 0.71-0.88]; active regular: 0.83 [95% CI, 0.72-0.97]; and inactive: 1.00 [95% CI, 0.90-1.11]). Findings were consistent at the median threshold of 230.4 minutes or more of MVPA per week, although associations with stroke were no longer significant (active WW: 0.89 [95% CI, 0.79-1.02]; active regular: 0.87 [95% CI, 0.74-1.02]; and inactive: 1.00 [95% CI, 0.90-1.11])., Conclusions and Relevance: Physical activity concentrated within 1 to 2 days was associated with similarly lower risk of cardiovascular outcomes to more evenly distributed activity.

Background Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision-making model. However, the impact and outcomes of this strategy remain unknown. Methods The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life-threatening cardiovascular conditions. The study will assess sports eligibility decision-making, exercise habits, psychosocial well-being, and long-term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to <35 years diagnosed with a confirmed cardiovascular condition or borderline finding with potential increased risk of major adverse cardiovascular events are eligible. Outcomes will be monitored for an initial 5-year follow-up period or until age 35, and metrics of psychosocial well-being and composite adverse cardiovascular events including arrhythmias, sudden cardiac arrest/sudden cardiac death, and evidence of disease progression will be compared among athletes who continue versus discontinue competitive sports participation. Conclusions The ORCCA study aims to assess the process and results of return to sport decision-making and to monitor major adverse cardiovascular events, exercise habits, and the psychosocial well-being among young competitive athletes diagnosed with confirmed cardiovascular conditions or borderline findings with potential increased risk of major adverse cardiovascular events. The results of this work will generate an evidence base to inform future guidelines.

Mitral annular calcification (MAC)-related mitral valve (MV) dysfunction is an increasingly recognized entity, which confers a high burden of morbidity and mortality. Although more common among women, there is a paucity of data regarding how the phenotype of MAC and the associated adverse clinical implications may differ between women and men. A total of 3,524 patients with extensive MAC and significant MAC-related MV dysfunction (i.e., transmitral gradient ≥3 mm Hg) were retrospectively analyzed from a large institutional database, with the goal of defining gender differences in clinical and echocardiographic characteristics and the prognostic importance of MAC-related MV dysfunction. We stratified patients into low- (3 to 5 mm Hg), moderate- (5 to 10 mm Hg), and high- (≥10 mm Hg) gradient groups and analyzed the gender differences in phenotype and outcome. The primary outcome was all-cause mortality, assessed using adjusted Cox regression models. Women represented the majority (67%) of subjects, were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had a lower burden of cardiovascular co-morbidities than men. Women had higher transmitral gradients (5.7 ± 2.7 vs 5.3 ± 2.6 mm Hg, p <0.001), more concentric hypertrophy (49% vs 33%), and more mitral regurgitation. The median survival was 3.4 years (95% confidence interval 3.0 to 3.6) among women and 3.0 years (95% confidence interval 2.6 to 4.5) among men. The adjusted survival was worse among men, and the prognostic impact of the transmitral gradient did not differ overall by gender. In conclusion, we describe important gender differences among patients with MAC-related MV dysfunction and show worse adjusted survival among men; although, the adverse prognostic impact of the transmitral gradient was similar between men and women., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: While young adults 18-24 years old bear a significant proportion of COVID-19 diagnoses, the risk factors for hospitalisation and severe COVID-19 complications in this population are poorly understood., Objective: The objective of this study was to identify risk factors for hospitalisation and other COVID-19 complications across the health spectrum of young adults diagnosed with COVID-19 infection., Study Design: Retrospective cohort study., Participants: Young adults (aged 18-24) with confirmed COVID-19 infection from the American Heart Association (AHA) COVID-19 Cardiovascular Disease Registry of hospitalised patients and the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study of collegiate athletes. The AHA registry included 636 young adults from 152 hospitals. The ORCCA registry consisted of 3653 competitive college athletes from 42 colleges and universities., Intervention: None (exposure to COVID-19)., Primary and Secondary Outcome Measures: Main outcomes included hospitalisation, death, major adverse cardiovascular events (MACE) and other severe clinical events., Results: In comparison to the ORCCA registry, patients in the AHA registry were more likely to be female (59% vs 33%); had higher average body mass index (BMI) (32.4 vs 25.6); and had increased prevalence of diabetes (10% vs 0.4%), hypertension (7% vs 0.6%), chronic kidney disease (2% vs 0%) and asthma (14% vs 8%), all with p<0.01. There were eight (2%) deaths in the AHA hospitalised registry compared with zero in the ORCCA cohort. BMI was a statistically significant predictor of death in the hospitalised cohort (OR 1.05, 95% CI 1.00, 1.10). No significant predictors of MACE or other severe clinical events were identified., Conclusions: The risk of cardiac events in young adults aged 18-24 diagnosed with COVID-19 infection is low. Patients who were hospitalised (AHA registry) were more likely to have pre-existing medical comorbidities and higher BMI than healthy collegiate athletes (ORCCA registry). Once hospitalised, elevated BMI is associated with increased mortality although other drivers of MACE and other severe clinical events remain unclear., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest: None declared.

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study is a large-scale prospective investigation evaluating the cardiovascular effects and outcomes of SARS-CoV-2 infection on young competitive athletes. This review provides an overview of the key results from the ORCCA study. Results from the ORCCA study have provided important insights into the clinical impact of SARS-CoV-2 infection on the cardiovascular health of young competitive athletes and informed contemporary screening and return to sport practices. Key results include defining a low prevalence of both cardiac involvement and adverse cardiovascular outcomes after SARS-CoV-2 infection and evaluating the utility of a return-to-play cardiac evaluation. Future aims of the ORCCA study include the longer-term evaluation of cardiovascular outcomes among athletes post-SARS-CoV-2 infection and the transition to investigating outcomes in young athletes with potentially high-risk genetic or structural cardiac diagnoses.

Preparticipation cardiovascular screening (PPCS) in young athletes is performed to detect conditions associated with sudden cardiac death. Many medical societies and sports governing bodies support the addition of a 12-lead electrocardiogram (ECG) to the history and physical to improve PPCS sensitivity. The current standard for ECG interpretation in athletes, the International Criteria, was developed to distinguish physiologic from pathologic ECG findings in athletes. Although application of the International Criteria has reduced the PPCS false-positive rate, interpretative challenges and potential areas of improvement remain. This review provides an overview of common pitfalls and future directions for ECG interpretation in athletes., Competing Interests: Disclosure The authors report no disclosures. Conflict of interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Initial protocols for return to play cardiac testing in young competitive athletes following SARS-CoV-2 infection recommended cardiac troponin (cTn) to screen for cardiac involvement. This study aimed to define the diagnostic yield of cTn in athletes undergoing cardiovascular testing following SARS-CoV-2 infection. Methods and Results This prospective, observational cohort study from ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) included collegiate athletes who underwent cTn testing as a component of return to play protocols following SARS-CoV-2 infection. The cTn values were stratified as undetectable, detectable but within normal limits, and abnormal (>99% percentile). The presence of probable or definite SARS-CoV-2 myocardial involvement was compared between those with normal versus abnormal cTn levels. A total of 3184/3685 (86%) athletes in the ORCCA database met the inclusion criteria for this study (age 20±1 years, 32% female athletes, 28% Black race). The median time from SARS-CoV-2 diagnosis to cTn testing was 13 days (interquartile range, 11, 18 days). The cTn levels were undetectable in 2942 athletes (92%), detectable but within normal limits in 210 athletes (7%), and abnormal in 32 athletes (1%). Of the 32 athletes with abnormal cTn testing, 19/32 (59%) underwent cardiac magnetic resonance imaging, 30/32 (94%) underwent transthoracic echocardiography, and 1/32 (3%) did not have cardiac imaging. One athlete with abnormal troponin met the criteria for definite or probable SARS-CoV-2 myocardial involvement. In the total cohort, 21/3184 (0.7%) had SARS-CoV-2 myocardial involvement, among whom 20/21 (95%) had normal troponin testing. Conclusions Abnormal cTn during routine return to play cardiac screening among competitive athletes following SARS-CoV-2 infection appears to have limited diagnostic utility.

Mitral annular calcification (MAC) is a common clinical finding and is associated with adverse clinical outcomes, but the clinical impact of MAC-related mitral valve (MV) dysfunction remains underappreciated. Patients with MAC frequently have stenotic, regurgitant, or mixed valvular disease, and this valvular dysfunction is increasingly recognized to be independently associated with worse prognosis. MAC-related MV dysfunction is a distinct pathophysiologic entity, and importantly much of the diagnostic and therapeutic paradigm from published rheumatic MV disease research cannot be applied in this context, leaving important gaps in our knowledge. This review summarizes the current epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes both an integrative definition and an overarching approach to this important and increasingly recognized clinical condition., Competing Interests: Funding Support and Author Disclosures This study was supported in part by a grant from the Ellison Foundation and by National Institutes of Health grant R01 HL141917 (Drs Levine and Hung). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms in young competitive athletes following SARS-CoV-2 infection., Methods: This observational cohort study from the Outcomes Registry for Cardiac Conditions in Athletes included 3597 US collegiate athletes after SARS-CoV-2 infection. Clinical characteristics, advanced diagnostic testing and SARS-CoV-2-associated sequelae were compared between athletes with persistent symptoms >3 weeks, exertional symptoms on return to exercise and those without persistent or exertional symptoms., Results: Among 3597 athletes (mean age 20 years (SD, 1 year), 34% female), data on persistent and exertional symptoms were reported in 3529 and 3393 athletes, respectively. Persistent symptoms >3 weeks were present in 44/3529 (1.2%) athletes with 2/3529 (0.06%) reporting symptoms >12 weeks. Exertional cardiopulmonary symptoms were present in 137/3393 (4.0%) athletes. Clinical evaluation and diagnostic testing led to the diagnosis of SARS-CoV-2-associated sequelae in 12/137 (8.8%) athletes with exertional symptoms (five cardiac involvement, two pneumonia, two inappropriate sinus tachycardia, two postural orthostatic tachycardia syndrome and one pleural effusion). No SARS-CoV-2-associated sequelae were identified in athletes with isolated persistent symptoms. Of athletes with chest pain on return to exercise who underwent cardiac MRI (CMR), 5/24 (20.8%) had probable or definite cardiac involvement. In contrast, no athlete with exertional symptoms without chest pain who underwent CMR (0/20) was diagnosed with probable or definite SARS-CoV-2 cardiac involvement., Conclusion: Collegiate athletes with SARS-CoV-2 infection have a low prevalence of persistent or exertional symptoms on return to exercise. Exertional cardiopulmonary symptoms, specifically chest pain, warrant a comprehensive evaluation., Competing Interests: Competing interests: JAD is Editor-in-Chief of BJSM and KGH is a Deputy Editor of BJSM. ALB has received funding from the National Institute of Health/ National Heart, Lung, and Blood Institute (NHLBI), the National Football Players Association, and the American Heart Association and receives compensation for his role as team cardiologist from the US Olympic Committee / US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. KGH has stock options for 98point6 for which she is also on the medical advisory board. MRP is on the Advisory Board for: Amgen, Bayer, Janssen, Heartflow, Medscape, and has research grant funding from NHLBI, Bayer, Janssen, Heartflow, Idorsia. and the Joel Cournette Foundation for research on athlete’s hearts., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Persistent or late-onset cardiopulmonary symptoms following COVID-19 may occur in athletes despite a benign initial course. We examined the yield of cardiac evaluation, including cardiopulmonary exercise testing (CPET), in athletes with cardiopulmonary symptoms after COVID-19, compared CPETs in these athletes and those without COVID-19 and evaluated longitudinal changes in CPET with improvement in symptoms., Methods: This prospective cohort study evaluated young (18-35 years old) athletes referred for cardiopulmonary symptoms that were present>28 days from COVID-19 diagnosis. CPET findings in post-COVID athletes were compared with a matched reference group of healthy athletes without COVID-19. Post-COVID athletes underwent repeat CPET between 3 and 6 months after initial evaluation., Results: Twenty-one consecutive post-COVID athletes with cardiopulmonary symptoms (21.9±3.9 years old, 43% female) were evaluated 3.0±2.1 months after diagnosis. No athlete had active inflammatory heart disease. CPET reproduced presenting symptoms in 86%. Compared with reference athletes (n=42), there was similar peak VO 2 but a higher prevalence of abnormal spirometry (42%) and low breathing reserve (42%). Thirteen athletes (62%) completed longitudinal follow-up (4.8±1.9 months). The majority (69%) had reduction in cardiopulmonary symptoms, accompanied by improvement in peak VO 2 and oxygen pulse, and reduction in resting and peak heart rate (all p<0.05)., Conclusion: Despite a high burden of cardiopulmonary symptoms after COVID-19, no athlete had active inflammatory heart disease. CPET was clinically useful to reproduce symptoms with either normal testing or identification of abnormal spirometry as a potential therapeutic target. Improvement in post-COVID symptoms was accompanied by improvements in CPET parameters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Oxygen uptake (V̇o 2 ) at exercise onset is determined in part by acceleration of pulmonary blood flow ([Formula: see text]). Impairments in the [Formula: see text] response can decrease exercise tolerance. Prior research has shown that voluntary respiratory maneuvers can augment venous return, but the corollary impacts on cardiac function, [Formula: see text] and early-exercise V̇o 2 remain uncertain. We examined 1 ) the cardiovascular effects of three distinct respiratory maneuvers (abdominal, AB; rib cage, RC; and deep breathing, DB) under resting conditions in healthy subjects ( Protocol 1 , n = 13), and 2 ) the impact of pre-exercise DB on pulmonary O 2 transfer during initiation of moderate-intensity exercise ( Protocol 2 , n = 8). In Protocol 1 , echocardiographic analysis showed increased right ventricular (RV) cardiac output and left ventricular (LV) cardiac output (RVCO and LVCO, respectively), following AB (by +23 ± 13 and +18 ± 15%, respectively, P < 0.05), RC (+23 ± 16; +14 ± 15%, P < 0.05), and DB (+27 ± 21; +23 ± 14%, P < 0.05). In Protocol 2 , DB performed for 12 breaths produced a pre-exercise increase in V̇o 2 (+801 ± 254 mL·min -1 over ∼6 s), presumably from increased [Formula: see text], followed by a reduction in pulmonary O 2 transfer during early phase exercise (first 20 s) compared with the control condition (149 ± 51 vs. 233 ± 65 mL, P < 0.05). We conclude that 1 ) respiratory maneuvers enhance RVCO and LVCO in healthy subjects under resting conditions, 2 ) AB, RC, and DB have similar effects on RVCO and LVCO, and 3 ) DB can increase [Formula: see text] before exercise onset. These findings suggest that pre-exercise respiratory maneuvers may represent a promising strategy to prime V̇o 2 kinetics and thereby to potentially improve exercise tolerance in patients with impaired cardiac function. NEW & NOTEWORTHY We demonstrate that different breathing maneuvers can augment both right and left-sided cardiac output in healthy subjects. These maneuvers, when performed immediately before exercise, result in a pre-exercise "cardiodynamic" increase in oxygen uptake (V̇o 2 ) associated with a subsequent reduction in the "cardiodynamic" V̇o 2 normally seen during early exercise. We conclude that pre-exercise breathing maneuvers are a plausible tool worthy of additional study to prime V̇o 2 kinetics and improve exercise tolerance in patients with cardiovascular disease.

Initial guidelines recommended a 12-lead electrocardiogram (ECG) in young competitive athletes following SARS-CoV-2 infection to screen for myocarditis. However, no data are available that detail ECG findings before and after SARS-CoV-2 infection in young athletes without clinical or imaging evidence of overt myocarditis. This study applied the International Criteria for ECG interpretation in a cohort of 378 collegiate athletes to compare ECG findings at baseline and during the acute phase of SARS-CoV-2 infection. Our results suggest that ECG changes can occur in the absence of definitive SARS-CoV-2 cardiac involvement in young competitive athletes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Cardiorespiratory fitness (CRF), as one of the most potent prognostic factors in medicine, is followed longitudinally to guide clinical management. Coronavirus disease 2019 (COVID-19) pandemic-related changes in lifestyle stand to influence CRF., Objective: To assess the influence of the pandemic on perceived CRF in athlete patients and evaluate how perceived CRF change was related to demographics, pre-pandemic measured CRF, and current physical activity (PA)., Design: Prospective cohort study, utilizing electronic survey., Setting: Tertiary care sports cardiology clinical practice., Participants: Adult athlete patients without COVID-19 with pre-pandemic measured CRF using cardiopulmonary exercise testing., Interventions: Not applicable., Main Outcome Measures: Perceived change in CRF since pandemic onset; association between perceived CRF change and demographics, PA, health status, and pre-pandemic measured CRF assessed via analysis of variance (ANOVA)., Results: Among 62 participants (male: 71%, 50.1 ± 12.1 years old), 40% (25/62) reported no change and 32% (20/62) reported an increase in perceived CRF since pandemic onset. Among the 27% (17/62) who reported a decrease in perceived CRF, in most (12/17), this was characterized as only mild. Demographics and pre-pandemic measured CRF did not differ across groups of perceived CRF change. Participants with a moderate or greater decrease in perceived CRF regarded their overall health (via Euro Quality of Life Visual Analogue Scale) as worse than other groups (ANOVA, p = .001). Although total PA was similar across groups, those who had improvement in perceived CRF reported higher levels of moderate intensity PA (ANOVA, p = .008)., Conclusions: The majority of participants perceived that they had maintained or improved CRF over the pandemic. Findings from this study suggest that a reduction in perceived CRF from pre-pandemic values in athletic patients in clinical practice may not result from population-wide pandemic changes in lifestyle. Worse health status and lower levels of moderate intensity PA were associated with perceived reduction in CRF over the pandemic in athlete patients., (© 2022 American Academy of Physical Medicine and Rehabilitation.)

To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFβ signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications., Competing Interests: This work was supported by the National Institutes of Health (R01AG061034 and R35HL15531 [to Dr Rosenzweig]; R01HL092577, R01HL128914, and K24HL105780 [to Dr Ellinor]; R01HL134893, R01HL140224, K24HL153669 [to Dr Ho]; T32HL094301 [to Dr Weber]; K08HL140200 [to Dr Rhee]; and K76AG064328 [to Dr Roh]), the Fondation Leducq (14CVD01 [to Dr Ellinor]), the American Heart Association (18SFRN34110082 [to Dr Ellinor]), a Sarnoff Cardiovascular Research Foundation Fellowship award (to Dr Trager), the Fred and Ines Yeatts Fund for Innovative Research (to Dr Roh), the Hassenfeld Scholars Award (to Dr Roh), Fast Grants, Emergent Ventures, Mercatus Center at George Mason University (to Dr Martinot), and a research grant from Bayer AG to the Broad Institute (to Drs Ellinor and Ho). Dr Ellinor is supported by a grant from Bayer AG to the Broad Institute focused on the genetics and therapeutics of cardiovascular diseases; and has served on advisory boards or consulted for Bayer AG, Quest Diagnostics, MyoKardia and Novartis. Dr Ho has received research grants from Bayer AG and Gilead Sciences; and has received research supplies from EcoNugenics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Aims: Accurate interpretation of cardiopulmonary exercise testing (CPET) relies on age, gender, and exercise modality-specific reference values. To date, clinically applicable CPET reference values derived from a source population of endurance athletes (EAs) have been lacking. The purpose of this study was to generate CPET reference values for use in the clinical assessment of EA., Methods and Results: Prospective data accrued during the clinical care of healthy EA were used to derive CPET reference values and to develop novel equations for V˙O2peak. The performance of these equations was compared to the contemporary standard of care equations and assessed in a discrete EA validation cohort. A total of 272 EA (age = 42 ± 15 years, female = 31%, V˙O2peak = 3.6 ± 0.83 L/min) met inclusion criteria and comprised the derivation cohort. V˙O2peak prediction equations derived from general population cohorts described a modest amount of V˙O2peak variability [R2 = 0.58-0.70, root mean square error (RMSE) = 0.46-0.54 L/min] but were mis-calibrated (calibration-in-the-large = 0.45-1.18 L/min) among EA leading to significant V˙O2peak underestimation. Newly derived, externally validated V˙O2peak prediction equations for EA that included age, sex, and height for both treadmill (R2 = 0.74, RMSE = 0.42 L/min) and cycle ergometer CPET (Cycle: R2 = 0.69, RMSE = 0.42 L/min) demonstrated improved accuracy., Conclusion: Commonly used V˙O2peak prediction equations derived from general population cohorts perform poorly among competitive EA. Newly derived CPET reference values including novel V˙O2peak prediction equations may improve the clinical utility of CPET in this rapidly growing patient population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The prevalence of mitral annular calcium (MAC) is increasing in our aging population. However, data regarding prognostication in MAC-related mitral valve (MV) disease remain limited. This retrospective observational study aims to explore the prognostic impact of systolic pulmonary artery pressure (SPAP) in MAC-related MV dysfunction and define its determinants. We identified 4,384 patients (mean age 78 ± 11 years and 69% female) with MAC-related MV dysfunction (documented transmitral gradient ≥3 mm Hg) from a large institutional echocardiographic database between 2001 and 2019. In Cox regression analysis, higher SPAP strongly associated with all-cause mortality, independent of cardiovascular risk factors and indices of MV dysfunction (adjusted hazard ratio 1.22 per 10 mm Hg SPAP increase, 95% confidence interval 1.17 to 1.27). Patients with SPAP ≥50 mm Hg had significantly higher mortality compared with SPAP <50 mm Hg (log-rank p <0.001), a finding that was consistent across different transmitral gradient subgroups (≤5, 5 to 10, and ≥10 mm Hg). Independent determinants of SPAP included the mean transmitral gradient, mitral regurgitation severity, left ventricular ejection fraction, and ≥moderate aortic stenosis (adjusted p <0.05), and atrial fibrillation and left atrial dimension. The impact of concomitant mitral regurgitation on SPAP decreased at higher transmitral gradients and was no longer significant at gradients ≥10 mm Hg (p = 0.100). In conclusion, SPAP strongly associates with mortality in MAC, independent of cardiovascular risk factors and indices of MAC-related MV dysfunction. These findings suggest an incremental role for SPAP in the risk stratification and prognostication in this increasingly prevalent condition with expanding the scope of possible interventions., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Mechanisms underlying sex differences in heart failure with preserved ejection fraction (HFpEF) are poorly understood. We sought to examine sex differences in measures of arterial stiffness and the association of arterial stiffness measures with left ventricular hemodynamic responses to exercise in men and women., Methods: We studied 83 men (mean age 62 years) and 107 women (mean age 59 years) with HFpEF who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial stiffness measurement (augmentation pressure [AP], augmentation index [AIx], and aortic pulse pressure [AoPP]). Sex differences were compared using multivariable linear regression. We examined the association of arterial stiffness with abnormal left ventricular diastolic response to exercise, defined as a rise in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO) ≥ 2 mmHg/L/min by using logistic regression models., Results: Women with HFpEF had increased arterial stiffness compared with men. AP was nearly 10 mmHg higher, and AIx was more than 10% higher in women compared with men (P < 0.0001 for both). Arterial stiffness measures were associated with a greater pulmonary capillary wedge pressure response to exercise, particularly among women. A 1-standard deviation higher AP was associated with > 3-fold increased odds of abnormal diastolic exercise response (AP: OR 3.16, 95% CI 1.34-7.42; P = 0.008 [women] vs OR 2.07, 95% CI 0.95-5.49; P = 0.15 [men]) with similar findings for AIx and AoPP., Conclusions: Arterial stiffness measures are significantly higher in women with HFpEF than in men and are associated with abnormally steep increases in pulmonary capillary wedge pressure with exercise, particularly in women. Arterial stiffness may preferentially contribute to abnormal diastolic function during exercise in women with HFpEF compared with men., Competing Interests: Conflicts of interest The authors have no conflicts of interest to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Although exercise testing guidelines define cutoffs for an exaggerated exercise systolic blood pressure (SBP) response, SBPs above these cutoffs are not uncommon in athletes given their high exercise capacity. Alternately, guidelines also specify a normal SBP response that accounts for metabolic equivalents (METs; mean [SD] of 10 [2] mm Hg per MET or 3.5 mL/kg/min oxygen consumption [V˙o 2 ]). SBP and V˙o 2 increase less during exercise in females than males. It is not clear if sex-based differences in exercise SBP are related to differences in V˙o 2 or if current recommendations for normal increase in SBP per MET produce reasonable estimates using measured METs (ie, V˙o 2 ) in athletes. We therefore examined sex-based differences in exercise SBP indexed to V˙o 2 in athletes with the goal of defining normative values for exercise SBP that account for fitness and sex., Methods: Using prospectively collected data from a single sports cardiology program, normotensive athlete patients were identified who had no relevant cardiopulmonary disease and had undergone cardiopulmonary exercise testing with cycle ergometry or treadmill. The relationship between ΔSBP (peak - rest) and ΔV˙o 2 (peak - rest) was examined in the total cohort and compared between sexes., Findings: A total of 413 athletes (mean [SD] age, 35.5 [14] years; 38% female; mean [SD] peak V˙o 2 , 46.0 [10.2] mL/kg/min, 127% [27%] predicted) met the inclusion criteria. The ΔSBP correlated with unadjusted ΔV˙o 2 (cycle: R 2  = 0.18, treadmill: R 2  = 0.12; P < 0.0001). Female athletes had lower mean (SD) peak SBP (cycle: 161 [15] vs 186 [24] mm Hg; treadmill: 165 [17] vs 180 [20] mm Hg; P < 0.05) than male athletes. Despite lower peak SBP, mean (SD) ΔSBP relative to unadjusted ΔV˙o 2 was higher in female than male athletes (cycle: 25.6 [7.2] vs 21.1 [7.3] mm Hg/L/min; treadmill: 21.6 [7.2] vs 17.0 [6.2] mm Hg/L/min; P < 0.05). When V˙o 2 was adjusted for body size and converted to METs, female and male athletes had similar mean (SD) ΔSBP /ΔMET (cycle: 6.0 [2.1] vs 5.8 [2.0] mm Hg/mL/kg/min; treadmill: 4.7 [1.8] vs 4.8 [1.7] mm Hg/mL/kg/min)., Implications: In this cohort of athletes without known cardiopulmonary disease, observed sex-based differences in peak exercise SBP were in part related to the differences in ΔV˙o 2 between male and female athletes. Despite lower peak SBP, ΔSBP/unadjusted ΔV˙o 2 was paradoxically higher in female athletes. Future work should define whether this finding reflects sex-based differences in the peripheral vascular response to exercise. In this athletic cohort, ΔSBP/ΔMET was similar between sexes and much lower than the ratio that has been proposed by guidelines to define a normal SBP response. Our observed ΔSBP/ΔMET, based on measured rather than estimated METs, provides a clinically useful estimate for normal peak SBP range in athletes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiopulmonary exercise testing (CPET) guidelines recommend analysis of the oxygen (O 2 ) pulse for a late exercise plateau in evaluation for obstructive coronary artery disease (OCAD). However, whether this O 2 pulse trajectory is within the range of normal has been debated, and the diagnostic performance of the O 2 pulse for OCAD in physically fit individuals, in whom V ˙ O 2 may be more likely to plateau, has not been evaluated. Using prospectively collected data from a sports cardiology program, patients were identified who were free of other cardiac disease and underwent clinically-indicated CPET within 90 days of invasive or computed tomography coronary angiography. The diagnostic performance of quantitative O 2 pulse metrics (late exercise slope, proportional change in slope during late exercise) and qualitative assessment for O 2 pulse plateau to predict OCAD was assessed. Among 104 patients (age:56 ± 12 years, 30% female, peak V ˙ O 2 119 ± 34% predicted), the diagnostic performance for OCAD (n = 24,23%) was poor for both quantitative and qualitative metrics reflecting an O 2 pulse plateau (late exercise slope: AUC = 0.55, sensitivity = 68%, specificity = 41%; proportional change in slope: AUC = 0.55, sensitivity = 91%, specificity = 18%; visual plateau/decline: AUC = 0.51, sensitivity = 33%, specificity = 67%). When O 2 pulse parameters were added to the electrocardiogram, the change in AUC was minimal (-0.01 to +0.02, p ≥ 0.05). Those patients without OCAD with a plateau or decline in O 2 pulse were fitter than those with linear augmentation (peak V ˙ O 2 133 ± 31% vs. 114 ± 36% predicted, p < 0.05) and had a longer exercise ramp time (9.5 ± 3.2 vs. 8.0 ± 2.5 min, p < 0.05). Overall, a plateau in O 2 pulse was not a useful predictor of OCAD in a physically fit population, indicating that the O 2 pulse should be integrated with other CPET parameters and may reflect a physiologic limitation of stroke volume and/or O 2 extraction during intense exercise., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Aims: Viral-induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)-like syndromes. COVID-19 can lead to myocardial damage and vascular injury. We hypothesised that COVID-19 patients frequently develop a HFpEF-like syndrome, and designed this study to explore this., Methods and Results: Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID-19 patients from April-November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID-19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA-PEFF score. A low (0-1 points), intermediate (2-4 points), and high (5-6 points) HFA-PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID-19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA-PEFF scores were more frequent in COVID-19 patients than controls (25% vs. 4%, P = 0.001). In COVID-19 patients, the HFA-PEFF score significantly correlated with age, estimated glomerular filtration rate, high-sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H 2 FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA-PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA-PEFF scores [median 5 (interquartile range 3-6) vs. 1 (0-3), P < 0.001] and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001)., Conclusion: Hospitalized COVID-19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID-19 patients., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: An upcoming national mandate will require consultation of appropriate use criteria (AUC) through a clinical decision support mechanism (CDSM) for advanced imaging. We aimed to evaluate our current ability to ascertain test appropriateness., Methods: We prospectively collected data on 288 consecutive stress tests and coronary computed tomography angiography studies for medical inpatients. Study appropriateness was determined independently by two physicians using the 2013 Multimodality AUC., Results: The median age of the study population was 66 years [interquartile range (IQR) 56, 75], 40.8% were female, and 52.8% had a history of coronary artery disease. Review of the electronic health record (EHR) alone was sufficient to deem appropriateness for 87.2% of cases. The most common reason it was insufficient was inability to determine if the patient could exercise (59.5%). After reviewing the EHR and pilot CDSM data together, appropriateness could be determined for 95.8% of the cases. The most common reason appropriateness could not be determined was that the exam indication was not addressed by an AUC criterion (83.3%)., Conclusion: In preparing for the mandate, it will be important for future CDSM to obtain information on the patient's ability to exercise and for future AUC to include additional indications that are not currently addressed., (© 2019. American Society of Nuclear Cardiology.)

Importance: Population-specific normative data are essential for the evaluation of competitive athletes. At present, there are limited data defining normal electrocardiographic (ECG) and echocardiographic values among elite US soccer players., Objective: To describe ECG and echocardiographic findings in healthy elite US soccer players., Design, Setting, and Participants: This cross-sectional study analyzed Fédération Internationale de Football Association-mandated screening sessions performed at US Soccer National Team training locations from January 2015 to December 2019. US women's and men's national team soccer players undergoing mandated cardiovascular screening were included., Main Outcomes and Measures: Normal training-related and abnormal ECG findings were reported using the International Recommendations for Electrocardiographic Interpretation in Athletes. Echocardiographic measurements of structural and functional parameters relevant to cardiovascular remodeling were assessed relative to American Society of Echocardiography guideline-defined normal ranges., Results: A total of 238 athletes (122 [51%] female; mean [SD] age, 20 [4] years; age range, 15-40 years) were included. Male athletes demonstrated a higher prevalence of normal training-related ECG findings, while female athletes were more likely to have abnormal ECG patterns (14 [11%] vs 0 in male cohort), largely accounted for by abnormal T-wave inversions. Echocardiography revealed no pathologic findings meeting criteria for sport restriction, but athletes frequently exceeded normal ranges for structural cardiac parameters responsive to exercise-induced remodeling including body surface area-indexed left ventricular (LV) mass (58 of 113 female athletes [51%] and 67 of 114 male athletes [59%]), indexed LV volume (89 of 115 female athletes [77%] and 76 of 111 male athletes [68%]), and LV wall thickness (37 of 122 female athletes [30%] and 47 of 116 male athletes [41%]). Age-stratified analysis revealed age-dependent increases in LV wall thickness, mass, and volumes among female athletes and LV wall thickness and mass among male athletes., Conclusions and Relevance: These data represent the first set of comprehensive normative values for elite US soccer players and one of the largest sport-specific echocardiographic remodeling studies in female athletes. Abnormal ECG findings were more common in female athletes, while both female and male athletes frequently exceeded clinical normality cut points for remodeling-associated echocardiographic parameters.

Background: Occult atrial fibrillation (AF) is an important contributor to cryptogenic stroke, yet remains difficult to unmask at presentation. This study investigated the predictive value of left atrial (LA) mechanics by strain echocardiography during stroke hospitalization for the presence of AF as detected on early 30-day monitoring and routine clinical follow-up., Methods: Left atrial mechanics were studied by strain echocardiography in a retrospective cohort of 191 patients with cryptogenic stroke and 30-day mobile cardiac outpatient telemetry poststroke to diagnose AF. After this, AF was diagnosed via routine clinical follow-up. The independent and incremental value of measures of LA size and mechanics (i.e., strain and strain rate in the reservoir, conduit, and booster pump phase) to predict AF on top of clinical characteristics was assessed., Results: Of 191 patients, 15% (n = 28) developed AF, of which 10 were observed during 30-day mobile cardiac outpatient telemetry and 18 were observed at a median follow-up of 25 (interquartile range, 10-43) months. Median time from embolic stroke to strain echocardiography was 1 day (interquartile range, 1-2 days). Left atrial mechanics were significantly worse in AF (P < .05 for all), despite largely similar baseline cardiovascular risk profile. Booster pump strain rate was the strongest predictor for AF, independent of age, LA volume index, E/e', and reservoir strain (odds ratio = 2.88 per SD increase; 95% confidence interval, 1.29-6.41; P = .010). Adding LA strain reservoir strain and booster pump function significantly enhanced a multivariate model to predict AF. Freedom from AF was significantly lower in subjects with a booster pump strain rate (at stroke presentation) worse than -0.67 sec -1 , as derived from receiver operator curve analysis (P < .001)., Conclusions: Left atrial mechanics and particularly the LA booster pump function assessed early during hospitalization for cryptogenic stroke can identify patients at greater likelihood of future diagnosis of AF. These findings could in part relate to LA mechanical stunning after spontaneous cardioversion, which-when identified by early strain echocardiography-can inform further risk stratification and decision-making., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to define the natural history of patients with mitral annular calcification (MAC)-related mitral valve dysfunction and to assess the prognostic importance of mean transmitral pressure gradient (MG) and impact of concomitant mitral regurgitation (MR)., Methods and Results: The institutional echocardiography database was examined from 2001 to 2019 for all patients with MAC and MG ≥3 mmHg. A total of 5754 patients were stratified by MG in low (3-5 mmHg, n = 3927), mid (5-10 mmHg, n = 1476), and high (≥10 mmHg, n = 351) gradient. The mean age was 78 ± 11 years, and 67% were female. MR was none/trace in 32%, mild in 42%, moderate in 23%, and severe in 3%. Primary outcome was all-cause mortality, and outcome models were adjusted for age, sex, and MAC-related risk factors (hypertension, diabetes, coronary artery disease, chronic kidney disease). Survival at 1, 5, and 10 years was 77%, 42%, and 18% in the low-gradient group; 73%, 38%, and 17% in the mid-gradient group; and 67%, 25%, and 11% in the high-gradient group, respectively (log-rank P < 0.001 between groups). MG was independently associated with mortality (adjusted HR 1.064 per 1 mmHg increase, 95% CI 1.049-1.080). MR severity was associated with mortality at low gradients (P < 0.001) but not at higher gradients (P = 0.166 and 0.372 in the mid- and high-gradient groups, respectively)., Conclusion: In MAC-related mitral valve dysfunction, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and MAC-related risk factors. Concomitant MR is associated with excess mortality in low-gradient ranges (3-5 mmHg) but gradually loses prognostic importance at higher gradients, indicating prognostic utility of transmitral gradient in MAC regardless of MR severity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Agitated saline contrast studies are an essential component of contemporary echocardiography. Agitated saline contrast plays a critical role in the elucidation of intracardiac versus intrapulmonary shunting and can have major therapeutic implications, particularly in light of the evolution of percutaneous treatment options for atrial septal defects or a patent foramen ovale. Despite their perceived simplicity, however, there are numerous pitfalls of these investigations that can occur during their performance and interpretation. As such, the authors review the "bubble study" in identifying intracardiac and extracardiac shunts, including the history of its development, the physics and physiology of contrast enhancement, how to optimally perform and interpret an agitated saline contrast study, and its safety in unique populations., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. To date, explanatory molecular mechanisms and the influence of exercise intensity remain poorly understood. Circulating factors are hypothesized to transduce some of the systemic effects of exercise. We sought to examine the role of exercise and exercise intensity on the human plasma proteome. We employed an aptamer-based method to examine 1,305 plasma proteins in 12 participants before and after exercise at two physiologically defined intensities (moderate and high) to determine the proteomic response. We demonstrate that the human plasma proteome is responsive to acute exercise in an intensity-dependent manner with enrichment analysis suggesting functional biological differences between the moderate and high intensity doses. Through integration of available genetic data, we estimate the effects of acute exercise on exercise-associated traits and find proteomic responses that may contribute to observed clinical effects on coronary artery disease and blood pressure regulation. In sum, we provide supportive evidence that moderate and high intensity exercise elicit different signaling responses, that exercise may act in part non-cell autonomously through circulating plasma proteins, and that plasma protein dynamics can simulate some the beneficial and adverse effects of acute exercise.

Masters athletes (MA), men and woman older than 35 years who participate in competitive athletics, is a rapidly growing population that is increasingly encountered in clinical cardiovascular practice. Although the high levels of exercise typically performed by MA confer numerous health advantages, no amount of exercise confers complete immunity from cardiovascular disease. The review was written to cover the clinical management of MA with cardiovascular disease. Focus is dedicated to four of the most common clinical scenarios including atrial fibrillation, myocardial fibrosis, coronary artery disease, and dilation of the ascending aorta.