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Background: Attaining guideline-recommended levels of physical activity is associated with substantially lower risk of cardiometabolic diseases., Objectives: Although physical activity commonly follows a weekend warrior pattern, in which most moderate-to-vigorous physical activity is concentrated in 1 to 2 days rather than spread more evenly across the week (regular), the effects of activity pattern on imaging-based biomarkers of cardiometabolic health are unknown., Methods: We analyzed 17,146 UK Biobank participants who wore accelerometers for 1 week, and later underwent cardiac magnetic resonance imaging. Activity was categorized as inactive, regular, or "weekend warrior". Associations between activity pattern and magnetic resonance imaging-derived visceral adipose tissue (VAT) and epicardial and pericardial adipose tissue (EPAT) were assessed using multiple linear regression adjusted for confounding factors., Results: Compared to inactive, VAT was progressively lower with weekend warrior (-0.71 L, 95% CI -0.78 to -0.64, P < 0.001) followed by regular activity (-0.96 L, 95% CI -1.04 to -0.88, P < 0.001). Observations were similar for EPAT (weekend warrior activity -2.84 cm 2 , 95% CI -3.20 to -2.49, P < 0.001; regular activity -3.62 cm 2 , 95% CI -4.03 to -3.20, P < 0.001). When compared directly, weekend warriors had modestly higher adipose tissue than regular activity (VAT difference 0.25 L, 95% CI 0.17-0.32, P < 0.001; EPAT 0.78 cm 2 , 95% CI 0.40-1.15, P < 0.001). No differences were observed after adjustment for total moderate-to-vigorous physical activity minutes (VAT 0.07 L, 95% CI -0.01 to 0.14, P = 0.09; EPAT 0.04 cm 2 , 95% CI -0.35 to 0.43, P = 0.84)., Conclusions: Guideline-adherent physical activity is associated with favorable quantitative measures of cardiometabolic health, with no differences based on activity pattern for a given activity volume., Competing Interests: Funding support and author disclosures Dr Kany is supported by the Walter Benjamin Fellowship from the Deutsche Forschungsgemeinschaft (521832260). Dr Rämö is supported by a research fellowship from the Sigrid Jusélius Foundation. Dr Pirruccello is supported by the NIH (K08HL159346). Dr Churchill is supported by the National Institutes of Health (K23HL15926201A1). Dr Guseh is supported by the American Heart Association (19AMFDP34990046) and the President and Fellows of Harvard College (5KL2TR002542-04). Dr Ellinor is supported by grants from the National Institutes of Health (1RO1HL092577, 1R01HL157635, 5R01HL139731), from the American Heart Association (18SFRN34230127, 961045), and from the European Union (MAESTRIA 965286). Dr Lubitz previously received support from NIH grants R01HL139731 and R01HL157635, and American Heart Association18SFRN34250007. Dr Al-Alusi is supported by the NIH (T32-HL007208). Dr Khurshid is supported by the NIH (K23HL169839-01) and the American Heart Association (2023CDA1050571). Dr Ellinor receives sponsored research support from Bayer AG, IBM Research, Bristol Myers Squibb, Pfizer, and Novo Nordisk; he has also served on advisory boards or consulted for MyoKardia and Bayer AG. Dr Lubitz is an employee of Novartis as of July 2022; has 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. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

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.

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.)

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.

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.)

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.

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.)

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.

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: 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.)

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: 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.)

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.

Background: Aortic valve area (AVA) ≤1.0 cm 2 is a defining characteristic of severe aortic stenosis (AS). AVA can be underestimated at low transvalvular flow rate. Yet, the impact of flow rate on prognostic value of AVA ≤1.0 cm 2 is unknown and is not incorporated into AS assessment., Objectives: This study aimed to evaluate the effect of flow rate on prognostic value of AVA in AS., Methods: In total, 1,131 patients with moderate or severe AS and complete clinical follow-up were included as part of a longitudinal database. The effect of flow rate (ratio of stroke volume to ejection time) on prognostic value of AVA ≤1.0 cm 2 for time to death was evaluated, adjusting for confounders. Sensitivity analysis was performed to identify the optimal cutoff for prognostic threshold of AVA. The findings were validated in a separate external longitudinal cohort of 939 patients., Results: Flow rate had a significant effect on prognostic value of AVA. AVA ≤1.0 cm 2 was not prognostic for mortality (p = 0.15) if AVA was measured at flow rates below median (≤242 ml/s). In contrast, AVA ≤1.0 cm 2 was highly prognostic for mortality (p = 0.003) if AVA was measured at flow rates above median (>242 ml/s). Findings were irrespective of multivariable adjustment for age, sex, and surgical/transcatheter aortic valve replacement (as time-dependent covariates); comorbidities; medications; and echocardiographic features. AVA ≤1.0 cm 2 was also not an independent predictor of mortality below median flow rate in the validation cohort. The optimal flow rate cutoff for prognostic threshold was 210 ml/s., Conclusions: Transvalvular flow rate determines prognostic value of AVA in AS. AVA measured at low flow rate is not a good prognostic marker and therefore not a good diagnostic marker for truly severe AS. Flow rate assessment should be incorporated into clinical diagnosis, classification, and prognosis of AS., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A 77-year-old patient presented with a mobile structure on the anterior mitral valve leaflet and was diagnosed with endocarditis. Subsequent imaging demonstrated this finding was consistent with a left atrial mitral valve chord. Recognition of this rare mitral valve anomaly is key to avoid overdiagnostics and/or overtreatment. ( Level of Difficulty: Beginner. )., (© 2020 The Authors.)

Background: There is increasing evidence to suggest that not all individuals with type 2 diabetes mellitus (T2DM) have equal risk for developing cardiovascular disease. We sought to compare the yield of testing for pre-clinical atherosclerosis with various approaches., Methods: 98 asymptomatic individuals with T2DM without known coronary artery disease (CAD) were enrolled in a prospective study and underwent carotid ultrasound, exercise treadmill testing (ETT), coronary artery calcium (CAC) scoring, and coronary computed tomography angiography (CTA)., Results: Of 98 subjects (average age 55 ± 6, 64 % female), 43 (44 %) had coronary plaque detectable on CTA, and 38 (39 %) had CAC score >0. By CTA, 16 (16 %) had coronary stenosis ≥50 %, including three subjects with CAC = 0. Subjects with coronary plaque had greater prevalence of carotid plaque (58 % vs. 38 %, p = 0.01) and greater carotid intima media thickness (0.80 ± 0.20 mm vs. 0.70 ± 0.11 mm, p = 0.02). Notably, 18 of 55 subjects (33 %) with normal CTA had carotid plaque. Eight subjects had a positive ETT, of whom five had ≥ 50 % coronary stenosis, two had <50 % stenosis, and one had no CAD. Among these tests, CAC scoring had the highest sensitivity and specificity for prediction of CAD., Conclusion: Among asymptomatic subjects with T2DM, a majority (56 %) had no CAD by CTA. When compared to CTA, CAC was the most accurate screening modality for detection of CAD, while ETT and carotid ultrasound were less sensitive and specific. However, 33 % of subjects with normal coronary CTA had carotid plaque, suggesting that screening for carotid plaque might better characterize stroke risk in such patients.

OBJECTIVE We evaluated relationships of oral glucose tolerance testing (OGTT)-derived measures of insulin sensitivity and pancreatic β-cell function with indices of diabetes complications in a cross-sectional study of patients with type 2 diabetes who are free of overt cardiovascular or renal disease. RESEARCH DESIGN AND METHODS A subset of participants from the Penn Diabetes Heart Study (n = 672; mean age 59 ± 8 years; 67% male; 60% Caucasian) underwent a standard 2-h, 75-g OGTT. Insulin sensitivity was estimated using the Matsuda Insulin Sensitivity Index (ISI), and β-cell function was estimated using the Insulinogenic Index. Multivariable modeling was used to analyze associations between quartiles of each index with coronary artery calcification (CAC) and microalbuminuria. RESULTS The Insulinogenic Index and Matsuda ISI had distinct associations with cardiometabolic risk factors. The top quartile of the Matsuda ISI had a negative association with CAC that remained significant after adjusting for traditional cardiovascular risk factors (Tobit ratio -0.78 [95% CI -1.51 to -0.05]; P = 0.035), but the Insulinogenic Index was not associated with CAC. Conversely, the highest quartile of the Insulinogenic Index, but not the Matsuda ISI, was associated with lower odds of microalbuminuria (OR 0.52 [95% CI 0.30-0.91]; P = 0.022); however, this association was attenuated in models that included duration of diabetes. CONCLUSIONS Lower β-cell function is associated with microalbuminuria, a microvascular complication, while impaired insulin sensitivity is associated with higher CAC, a predictor of macrovascular complications. Despite these pathophysiological insights, the Matsuda ISI and Insulinogenic Index are unlikely to be translated into clinical use in type 2 diabetes beyond established clinical variables, such as obesity or duration of diabetes.