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Importance: Aortic dilatation is frequently encountered in clinical practice among aging endurance athletes, but the distribution of aortic sizes in this population is unknown. It is additionally uncertain whether this may represent aortic adaptation to long-term exercise, similar to the well-established process of ventricular remodeling., Objective: To assess the prevalence of aortic dilatation among long-term masters-level male and female athletes with about 2 decades of exercise exposure., Design, Setting, and Participants: This cross-sectional study evaluated aortic size in veteran endurance athletes. Masters-level rowers and runners aged 50 to 75 years were enrolled from competitive athletic events across the United States from February to October 2018. Analysis began January 2019., Exposures: Long-term endurance exercise., Main Outcomes and Measures: The primary outcome was aortic size at the sinuses of Valsalva and the ascending aorta, measured using transthoracic echocardiography in accordance with contemporary guidelines. Aortic dimensions were compared with age, sex, and body size-adjusted predictions from published nomograms, and z scores were calculated where applicable., Results: Among 442 athletes (mean [SD] age, 61 [6] years; 267 men [60%]; 228 rowers [52%]; 214 runners [48%]), clinically relevant aortic dilatation, defined by a diameter at sinuses of Valsalva or ascending aorta of 40 mm or larger, was found in 21% (n = 94) of all participants (83 men [31%] and 11 women [6%]). When compared with published nomograms, the distribution of measured aortic size displayed a rightward shift with a rightward tail (all P < .001). Overall, 105 individuals (24%) had at least 1 z score of 2 or more, indicating an aortic measurement greater than 2 SDs above the population mean. In multivariate models adjusting for age, sex, body size, hypertension, and statin use, both elite competitor status (rowing participation in world championships or Olympics or marathon time under 2 hours and 45 minutes) and sport type (rowing) were independently associated with aortic size., Conclusions and Relevance: Clinically relevant aortic dilatation is common among aging endurance athletes, raising the possibility of vascular remodeling in response to long-term exercise. Longitudinal follow-up is warranted to establish corollary clinical outcomes in this population.

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.)

Clinical guidelines advocate for customization of exercise testing to address patient-specific diagnostic goals, including reproduction of presenting exertional symptoms. However, the diagnostic yield of adding customized exercise testing to graded exercise in patients presenting with exertional complaints has not been rigorously examined and is the focus of this study. Using prospectively collected data, we analyzed the diagnostic yield of customized additional exercise provocation following inconclusive graded exercise test with measurement of gas exchange. Additional testing was defined as "positive" if it revealed a clinically-actionable diagnosis related to the chief complaint or reproduced symptoms in the absence of an explanatory diagnosis or pathology. Of 1,110 patients who completed a graded test, 122 (11%) symptomatic patients underwent additional customized exercise testing (e.g., sprint intervals and race simulations). Compared with those who did not undergo additional testing, this group was younger (29 [interquartile range 19 to 45] vs 46 [25 to 58] year old) and disproportionately female (43% vs 27%). Presenting symptoms included palpitations (46%), lightheadedness/syncope (25%), chest pain (14%), dyspnea (11%), and exertional intolerance (3%). Additional testing was "positive" in 48 of 122 (39%) of patients by revealing a clinically actionable diagnosis in 26 of 48 (54%) or reproducing symptoms without an explanatory diagnosis in 22 of 48 (46%). In conclusion, while patient-centered customization of exercise testing is suggested by clinical guidelines, these data are the first to demonstrate that the selective addition of customized exercise provocation following inconclusive graded exercise testing improves the diagnostic yield of exercise assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Professional American-style football players are among the largest athletes across contemporary sporting disciplines. Weight gain during football participation is common, but the health implications of this early-life weight gain remain incompletely understood. We sought to define weight trajectories of former professional American-style football athletes and to establish their relationship with 5 common health afflictions (cardiovascular disease, cardiometabolic disease, neurocognitive impairment, sleep apnea, and chronic pain)., Methods: A health survey was distributed to former National Football League (NFL) players. Former players reported body weight at 4 time points (high school, college, professional, and time of survey response) as well as maximal retirement weight. Logistic regression was used to assess associations between weight gain during football participation and health affliction., Results: In this cohort of former NFL players (n = 3,506, age 53 ± 14 years), mean weight increase from high school to time of survey response was 40 ± 36 pounds, with the majority of weight gain occurring during periods of football participation (high-school-to-college and college-to-professional). The prevalence of health afflictions ranged from 9% (cardiovascular disease) to 28% (chronic pain). Weight gain during football participation was independently associated with risk of multiple later-life health afflictions in models adjusted for football exposure, lifestyle variables, and post-career weight gain., Conclusions: Early-life weight gain among American-style football athletes is common and is associated with risk of adverse health profiles during later-life. These findings establish football-associated weight gain as a key predictor of post-career health and raise important questions about the central role of targeted weight gain in this population., (Copyright © 2018. Published by Elsevier Inc.)

Opinion Statement: Cardiovascular remodeling in response to sustained moderate and high-intensity exercise is a well-established phenomenon. Following more than a century of work focused on the left ventricle (LV), remodeling of the right side of the heart has recently become a topic of considerable scientific and clinical interest. Morphologic and functional changes have now been well documented in the right ventricle (RV) after isolated bouts of endurance exercise and in association with long-term sustained training. Although exercise-induced cardiac remodeling is classically viewed as an adaptive, clinically benign process, it has recently been hypothesized that repetitive bouts of intense exercise may trigger pathologic changes in the RV characterized by patchy fibrosis and a predisposition to arrhythmia. At present, this concept remains speculative due to the absence of definitive clinical data. While we await scientific clarification of this intriguing hypothesis, several practical clinical considerations are noteworthy. RV dilation is common among trained endurance athletes. As such, asymptomatic athletes with RV dilation do not require additional diagnostic evaluation unless dilation is accompanied by substantial decrements in systolic function or other structural abnormalities suggestive of genetic heart disease. In contrast, RV dilation among athletes with either symptoms or a family history of genetic heart disease requires extensive multi-modality assessment including maximal effort-limited exercise testing, ambulatory rhythm monitoring, advanced non-invasive imaging, and invasive electrophysiology study. This review will discuss the contemporary understanding of how the RV responds to exercise with an emphasis on the relevance of this phenomenon in clinical cardiovascular practice.

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.

Background: Calcification of the thoracic aorta is a risk factor for cardiovascular disease and peripheral arterial disease but has not been well studied in diabetics. In addition, many studies consider aortic calcium as a single anatomic entity, whereas calcification of the ascending and descending portions of the thoracic aorta may represent separate phenotypes. We sought to characterize the prevalence of ascending and descending aortic calcium among diabetics and to assess their associations with cardiovascular risk factors, coronary artery calcium, and peripheral arterial disease., Methods: Within the Penn Diabetes Heart Study, a cross-sectional study of subjects with type 2 diabetes mellitus but without coronary or renal disease, we quantified Agatston scores of the ascending and descending thoracic aorta in 1739 subjects (63% male, 61% Caucasian). Multivariate logistic and Tobit regressions were used to assess associations with cardiovascular risk factors, coronary calcium, and peripheral arterial disease., Results: Of all subjects, 54% had thoracic aortic calcium; of these, 37% had calcium solely in the ascending thoracic aorta and 20% solely in the descending thoracic aorta. In multivariate regression, age, Caucasian race, systolic blood pressure, low-density lipoprotein cholesterol, smoking, and diabetes duration were independently associated with calcium of both the ascending and descending thoracic aorta (P < .001 for all). Ascending and descending aortic calcium were each independently associated with coronary calcium in multivariate regression, but only calcification of the descending thoracic aortic was associated with low ankle-brachial index., Conclusion: Ascending and descending thoracic aortic calcium have similar associations with traditional cardiovascular risk factors in diabetics and are independently associated with coronary artery calcium. Only calcium in the descending aorta is associated with peripheral arterial disease. Delineation of both phenotypes may provide information about the individualized vascular disease and risk profile of patients with type 2 diabetes mellitus., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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.

Objective: Ankle-brachial index (ABI) screening is recommended for the detection of asymptomatic peripheral arterial disease (PAD) in at-risk populations, including diabetics. A low ABI identifies obstructive lower extremity vascular disease and predicts CVD events and increased mortality. A high ABI represents non-compressible arterial disease (NCAD), and is also associated with increased mortality and vascular events. Our objective is to investigate whether low and high ABI have distinct patterns of association with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis in individuals with type-II diabetes mellitus., Methods: The Penn Diabetes Heart Study (PDHS) is a prospective observational cohort of diabetic individuals without clinically evident CVD. Multivariate logistic and Tobit linear regression were used to compare CVD risk factors and coronary artery (CAC) among 1863 subjects with PAD (ABI ≤ 0.9), NCAD (ABI ≥ 1.4 or non-compressible) or normal ABI (0.91-1.39)., Results: Compared to those with normal ABI, PAD was associated with smoking, obesity, and lower HDL-c; while diabetes duration and reduced renal function were associated with NCAD. Both PAD and NCAD were independently associated with increased CAC compared to those with normal ABI, and these relationships were not attenuated in multiply adjusted models., Conclusion: NCAD bears a distinct relationship to traditional CVD risk factors among diabetics, though like PAD is independently associated with increased CAC. These findings support the recognition of NCAD as a high-risk phenotype and provide additional relevance to ABI screening in diabetics., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Mitral annular calcification (MAC) is a degenerative process of the mitral annulus associated with cardiac disease and stroke. Although thought to be more prevalent in type 2 diabetes (T2DM), MAC remains poorly characterized in this population, due to confounding by renal and cardiac disease. Our goal was to study the risk factors for MAC in a sample of T2DM subjects without renal and cardiac disease., Methods: The Penn Diabetes Heart Study (PDHS) is a cross-sectional study of diabetic individuals without clinical cardiovascular or renal disease. We quantified and analyzed MAC Agatston scores in baseline cardiac CTs from 1753 individuals. Logistic and tobit regression were used to assess MAC's relationship with risk factors and coronary artery calcium (CAC)., Results: MAC was present in 12.0% of subjects, with a median Agatston score of 72.3 [Interquartile range (22.2-256.9)]. Older age, female gender, Caucasian race, and longer diabetes duration were independently associated with both the presence and extent MAC even after controlling for CAC; however, hypertension, hyperlipidemia, tobacco use, CRP levels, and other comorbidities were not associated. CAC was strongly associated with MAC [OR of 4.0 (95% CI 2.4-6.6)] in multivariable models., Conclusions: Age, female gender, Caucasian race, and diabetes duration were associated with the presence and extent of MAC in T2DM subjects, independent of CAC, which was also strongly associated with MAC. These data suggest that additional mechanisms for MAC formation in diabetics may exist which are distinct from those related to generalized atherosclerosis and deserve further investigation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)