Distal Upper Extremity Arterial Calcification as a Predictor for Subclinical Coronary Artery Disease by Coronary Artery Calcium Scoring.

Several studies have linked calcification of the thoracic and lower extremity arterial trunks to an increased risk of developing coronary artery disease (CAD). Calcifications of the radial and/or ulnar artery are regularly identified in hand/wrist x-rays; however, the clinical relevance of these findings as related to identifying subclinical CAD is not well understood. Associations between CAD and upper extremity calcifications have been reported, but the timeline is unclear. The purpose of this study was to evaluate the association between upper extremity arterial calcifications on hand radiographs with CAD by coronary artery calcification (CAC) scoring in patients with no known history of CAD. This is a pilot single-center, prospective, matched cohort study. We included patients with no known history of CAD, related symptoms, or major risk factors. We recruited five patients with calcifications (cal+) and five patients matched by age, race, sex, and medical history but without calcifications (cal-). CAC scores were determined from computed tomography scanning, and lipid profile was evaluated. In the cal+ group, the mean CAC total score was 244.1; in the control (cal-) group, it was 85.2. The mean total cholesterol levels were 220.8 mg per dL and 167 mg per dL in the cal+ and cal- groups, respectively. Two cal+ patients with CAC scores of 937 and 669 died shortly after being enrolled in our study. Preliminary findings suggest that calcifications in the radial or ulnar artery in otherwise asymptomatic patients with no history of CAD may be an independent sign of CAD.

Electrocardiographic Findings in Female Professional Basketball Athletes.

Importance: Previous studies of professional basketball athletes have characterized manifestations of athletic remodeling by echocardiography and electrocardiography (ECG) in males and echocardiography in females. There is a paucity of female, basketball-specific ECG data. Objective: To generate reference range ECG data for female professional basketball athletes. Design, Setting, and Participants: This is a cross-sectional study of ECGs performed on female professional basketball athletes. The Women's National Basketball Association mandates annual preseason ECGs and echocardiograms for each athlete and has partnered with Columbia University Irving Medical Center to annually review these studies. Data for this study were collected during preseason ECG and echocardiography cardiac screening between April and May 2022. Data analysis was performed between February and July 2023. Exposure: Athlete ECGs and echocardiograms were sent to Columbia University Irving Medical Center for core lab analysis. Main Outcomes and Measures: Quantitative ECG variables were measured. ECG data were qualitatively analyzed for training-related and abnormal findings using the International Recommendations for Electrocardiographic Interpretation in Athletes. Findings from ECGs were compared with corresponding echocardiographic data. Results: There were a total of 173 athletes (mean [SD] age 26.5 [4.1] years; mean [SD] height, 183.4 [9.1] cm; mean [SD] body surface area, 2.0 [0.2] m2), including 129 Black athletes (74.5%) and 40 White athletes (23.1%). By international criteria, 136 athletes (78.6%) had training-related ECG changes and 8 athletes (4.6%) had abnormal ECG findings. Among athletes with at least 1 training-related ECG finding, left ventricular structural adaptations associated with athletic remodeling were present in 64 athletes (47.1%). Increased relative wall thickness, reflecting concentric left ventricular geometry, was more prevalent in athletes with the repolarization variant demonstrating convex ST elevation combined with T-wave inversions in leads V1 to V4 (6 of 12 athletes [50.0%]) than in athletes with early repolarization (5 of 42 athletes [11.9%]) (odds ratio, 7.40; 95% CI, 1.71-32.09; P = .01). Abnormal ECG findings included T-wave inversions (3 athletes [1.7%]), Q waves (2 athletes [1.2%]), prolonged QTc interval (2 athletes [1.2%]), and frequent premature ventricular contractions (1 athlete [0.6%]). Conclusions and Relevance: This cross-sectional study provides reference ECG data for elite female basketball athletes. International criteria-defined training-related findings were common, whereas abnormal ECG findings were rare in this athlete group. These reference data may assist basketball programs and health care professionals using ECGs in screening for female athletes and may be used as a stimulus for future female-specific ECG inquiries.

Cardiovascular Safety of the COVID-19 Vaccine in Team USA Athletes.

BACKGROUND: Despite reassuring scientific data, the lay press and social media continue to propagate largely unsubstantiated claims that a significant number of athletes have died from cardiovascular complications related to COVID-19 vaccines. The present study sought to determine the incidence of COVID-19 vaccine cardiovascular complications in Team USA athletes. HYPOTHESIS: It was predicted that there would be a low incidence of cardiovascular complications from COVID-19 vaccination in Team USA athletes. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS: A retrospective review was conducted on the United States Olympic and Paralympic Committee electronic medical record, inclusive of athletes who represented Team USA in the 2020 Tokyo and 2022 Beijing Olympic and Paralympic Games, for COVID-19 vaccine cardiac complications including sudden cardiac arrest/death, myocarditis, pericarditis, and myopericarditis. Vaccination status (ie, fully vaccinated, yes or no), date of vaccination and eligible boosters, and type of vaccination during the study period were abstracted from the electronic medical record. RESULTS: A total of 1229 athletes represented Team USA during the 2020 Tokyo (Olympic, 697; Paralympic, 237) and 2022 Beijing Games (Olympic, 229; Paralympic, 66). For the 2020 Tokyo Games, 73.8% of Olympians and 80.6% of Paralympians with available vaccination status had completed a primary vaccine series. For the 2022 Beijing Games, 100% of Olympians and Paralympians with available vaccination status were fully vaccinated. No athletes suffered sudden cardiac arrest/death or were diagnosed with myocarditis, pericarditis, or myopericarditis after COVID-19 vaccination. CONCLUSION: The data demonstrate an overall willingness of elite athletes to receive recommended COVID-19 vaccination coupled with a complete absence of vaccine-related cardiac complications in >1 year of follow-up. CLINICAL RELEVANCE: Supposedly, this is the first study to investigate the incidence of COVID-19 vaccine cardiovascular complications in elite athletes. These data are an important first step to better inform cardiologists and sports medicine physicians who care for elite athletes.

Impact of Sex on Cardiovascular Adaptations to Exercise: JACC Review Topic of the Week.

Routine exercise leads to cardiovascular adaptations that differ based on sex. Use of cardiac testing to screen athletes has driven research to define how these sex-based adaptations manifest on the electrocardiogram and cardiac imaging. Importantly, sex-based differences in cardiovascular structure and outcomes in athletes often parallel findings in the general population, underscoring the importance of understanding their mechanisms. Substantial gaps exist in the understanding of why cardiovascular adaptations and outcomes related to exercise differ by sex because of underrepresentation of female participants in research. As female sports participation rates have increased dramatically over several decades, it also remains unknown if differences observed in older athletes reflect biological mechanisms vs less lifetime access to sports in females. In this review, we will assess the effect of sex on cardiovascular adaptations and outcomes related to exercise, identify the impact of sex hormones on exercise performance, and highlight key areas for future research.

A Cyclist on a Tricyclic: Exercise Intolerance Due to Chronotropic Incompetence.

Depression in athletes is prevalent, and antidepressant treatment may have a cardiovascular impact. We present a case, documented by serial exercise testing, of exertional intolerance due to chronotropic incompetence associated with tricyclic antidepressant use. This case underscores the importance of understanding the mechanism of action and side effects of antidepressants. (Level of Difficulty: Advanced.).

Updated Blood Pressure Guidelines: Implications for Athletes.

PURPOSE OF REVIEW: To review the prevalence, short- and long-term impact of exercise on blood pressure, and the evaluation and treatment of hypertension in competitive athletes. RECENT FINDINGS: Due, in part, to inconsistencies in measurement and the definitions used, the true prevalence of hypertension is unknown as reports range from 0 to 83%. With recent changes in the blood pressure guidelines, the proportion of athletes that meet criteria for elevated blood pressure or stage 1 hypertension has increased dramatically with over one-third of collegiate and professional athletes meeting criteria for hypertension. Data consistently show that American-style football players, particularly linemen, display the highest rates of hypertension. These athletes typically have a larger body mass index, higher body fat percentage, and weight gain in serial follow-up. Many athletes with hypertension have traditional risk factors, and, to date, there is no evidence of a causal relationship between long-term sport participation and increased risk of developing hypertension. Many more athletes now meet criteria for hypertension, given the updated blood pressure guidelines. This should be taken as an opportunity for early intervention, as athletes are not immune to the development of cardiovascular risk factors and disease.

Differentiating Physiology from Pathology: The Gray Zones of the Athlete's Heart.

Routine vigorous exercise can lead to electrical, structural, and functional adaptations that can enhance exercise performance. There are several factors that determine the type and magnitude of exercise-induced cardiac remodeling (EICR) in trained athletes. In some athletes with pronounced cardiac remodeling, there can be an overlap in morphologic features with mild forms of cardiomyopathy creating gray zone scenarios whereby distinguishing health from disease can be difficult. An integrated clinical approach that factors athlete-specific characteristics (sex, size, sport, ethnicity, and training history) and findings from multimodality imaging are essential to help make this distinction.

Exercise and the Female Heart.

Female participation in sport has increased sharply during the last few decades, and for the third straight Olympic Games, there were more women than men on the US roster for the 2020 Tokyo Games. Given this, an understanding of the differences between men and women with respect to exercise-induced cardiac remodeling is critical for those caring for female athletes. Recent studies have provided insight into female-specific cardiac remodeling and have enhanced our understanding on the upper limits of cardiac remodeling in female athletes and how these adaptations compare with sedentary females, male athletes, and cardiomyopathies. Female athletes display fewer signs of adaptive remodeling on ECG compared with male athletes. Structurally, male athletes have larger absolute cardiac dimensions, but female athletes have similar or larger chamber size when adjusted for body size. Female athletes have a lower incidence of sudden cardiac arrest or death compared with male athletes in the early competitive years (high school, college, and professional) and in the masters athlete years. In addition, female athletes are less likely to have coronary disease and atrial fibrillation compared with male athletes. Data on longevity indicate that female athletes live longer than their sedentary counterparts. Unlike men, there has been no convincing association of extreme exercise and cardiovascular disease in longer-term endurance female athletes. The underlying mechanisms of these sex-based differences are not very well understood, and future studies are warranted to better understand the mechanisms of cardiac adaptation in female athletes.

Exercise-Induced Cardiovascular Adaptations and Approach to Exercise and Cardiovascular Disease: JACC State-of-the-Art Review.

The role of the sports cardiologist has evolved into an essential component of the medical care of athletes. In addition to the improvement in health outcomes caused by reductions in cardiovascular risk, exercise results in adaptations in cardiovascular structure and function, termed exercise-induced cardiac remodeling. As diagnostic modalities have evolved over the last century, we have learned much about the healthy athletic adaptation that occurs with exercise. Sports cardiologists care for those with known or previously unknown cardiovascular conditions, distinguish findings on testing as physiological adaptation or pathological changes, and provide evidence-based and "best judgment" assessment of the risks of sports participation. We review the effects of exercise on the heart, the approach to common clinical scenarios in sports cardiology, and the importance of a patient/athlete-centered, shared decision-making approach in the care provided to athletes.

Resumption of Sport at the United States Olympic and Paralympic Training Facilities During the COVID-19 Pandemic.

In this brief report, we describe the safety of reopening US Olympic and Paralympic Training facilities (USOPTFs) during the coronavirus disease 2019 (COVID-19) pandemic from July 2020 through October 2020. We evaluated the prevalence of COVID-19 infection at the time of reentry and cardiopulmonary sequelae of COVID-19 in elite athletes. All athletes returning to a USOPTF were required to go through a reentry protocol consisting of an electronic health history, a 6-day quarantine including twice-daily symptom surveys, COVID-19 polymerase chain reaction and antibody testing, physical examination, 12-lead electrocardiogram, high-sensitivity cardiac troponin I, and pulmonary function testing. Athletes with current or prior COVID-19 infection also underwent an echocardiogram, cardiology consultation, and additional testing as indicated. All athletes followed rigorous infection prevention measures and minimized contact with the outside community following reentry. At the time of this report, 301 athletes completed the reentry protocol among which 14 (4.7%) tested positive for active (positive polymerase chain reaction test, n = 3) or prior (positive antibody test, n = 11) COVID-19 infection. During the study period, this cohort accrued 14,916 days living and training at USOPTFs. Only one (0.3%) athlete was subsequently diagnosed with a new COVID-19 infection. No cardiopulmonary pathology attributable to COVID-19 was detected. Our findings suggest that residential elite athlete training facilities can successfully resume activity during the COVID-19 pandemic when strict reentry and infection prevention measures are followed. Dissemination of our reentry quarantine and screening protocols with COVID-19 mitigation measures may assist the global sports and medical community develop best practices for reopening of similar training centers.

Cardiovascular risk among ultra-endurance runners.

BACKGROUND: Our objective was to determine the prevalence and clinical correlates of conventional cardiovascular risk factors among ultra-endurance marathon runners. METHODS: An electronic internet survey to characterize modifiable cardiovascular risk factors including diabetes, hypertension, dyslipidemia, tobacco exposure and obesity (BMI>30) among competitive ultra-endurance runners. RESULTS: Among 290 respondents (mean±SD, 42±11 years, 31.4% female), 106 (36.6%) had at least one established cardiovascular risk factor. Female sex, younger age and participation in competitive high school or collegiate sports were associated with freedom from cardiovascular risk factors. There were no significant associations between risk factor status and either hours per week of running training (risk factor negative: 10±7 vs. risk factor positive: 11±8 hours, P=0.42) or years of ultra-endurance competition (6±8 vs. 7±9 years, P=0.38). Runners with at least one cardiovascular risk factor were more likely to have had personal or peer concerns about excessive alcohol use. CONCLUSIONS: Conventional cardiovascular risk factors are common among ultra-endurance runners. Early-life participation in competitive sports, rather than adult exercise habits, is associated with freedom from the development of cardiovascular risk factors during middle age. Determining mechanistic explanations for the legacy effect of early life exercise as a means to reduce cardiovascular risk among aging athletes represents an important area of future work.

The ELISA Detectability and Potency of Pegfilgrastim Decrease in Physiological Conditions: Key Roles for Aggregation and Individual Variability.

PEGylated recombinant human granulocyte colony stimulating factor (pegfilgrastim) is used clinically to accelerate immune reconstitution following chemotherapy and is being pursued for biosimilar development. One challenge to overcome in pegfilgrastim biosimilar development is establishing pharmacokinetic (PK) similarity, which is partly due to the degree of PK variability. We herein report that commercially available G-CSF and PEG ELISA detection kits have different capacities to detect pegfilgrastim aggregates that rapidly form in vitro in physiological conditions. These aggregates can be observed using SDS-PAGE, size-exclusion chromatography, dynamic light scattering, and real-time NMR analysis and are associated with decreased bioactivity as reflected by reduced drug-induced cellular proliferation and STAT3 phosphorylation. Furthermore, individual variability in the stability and detectability of pegfilgrastim in human sera is also observed. Pegfilgrastim levels display marked subject variability in sera from healthy donors incubated at 37 °C. The stability patterns of pegfilgrastim closely match the stability patterns of filgrastim, consistent with a key role for pegfilgrastim's G-CSF moiety in driving formation of inactive aggregates. Taken together, our results indicate that individual variability and ELISA specificity for inactive aggregates are key factors to consider when designing and interpreting studies involving the measurement of serum pegfilgrastim concentrations.

Ultrasound imaging in musculoskeletal injuries-What the Orthopaedic surgeon needs to know.

Patients with musculoskeletal complaints have either been ignored or advised investigations far beyond their means or comfort. Focusing attention only on spine and head restricted the evaluation in cases of trauma and were followed up only if the injuries were life threatening. In the same vein, the extremities often got overlooked or at best were evaluated only by plain radiographs. Soft tissue injuries were therefore often missed and not only raised the morbidity in the patient but also dissatisfaction towards the treating physician. Recent exponential improvement in medical ultrasound technology has revolutionised the field of musculoskeletal imaging. Cutting-edge technology using state-of-the-art machines and high-frequency transducers have placed it in a stronger position as compared to in the past in many aspects of musculoskeletal imaging. Also, with better techniques and understanding of the modality, under given set of circumstances MSK ultrasound has far reaching results allowing for detailed evaluation of soft tissues including nerves, ligaments and tendons.

Catecholamine response to exercise in patients with non-obstructive hypertrophic cardiomyopathy.

KEY POINTS: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). As a result, the majority of patients with HCM deliberately reduce their habitual physical activity after diagnosis and this lifestyle change puts them at risk for sequelae of a sedentary lifestyle: weight gain, hypertension, hyperlipidaemia, insulin resistance, coronary artery disease, and increased morbidity and mortality. We show that plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold, a parameter that can be defined during cardiopulmonary exercise testing, but rise rapidly at higher intensities of exercise. These findings suggest that cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM. ABSTRACT: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). However, the impact of exercise intensity on plasma catecholamine levels among HCM patients has not been rigorously defined. We conducted a prospective observational case-control study of men with non-obstructive HCM and age-matched controls. Laboratory-based cardiopulmonary exercise testing coupled with serial phlebotomy was used to define the relationship between exercise intensity and plasma catecholamine levels. Compared to controls (C, n = 5), HCM participants (H, n = 9) demonstrated higher left ventricular mass index (115 ± 20 vs. 90 ± 16 g/m2 , P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P < 0.001) but similar body mass index, resting heart rate, peak oxygen consumption (H = 40 ± 13 vs. C = 42 ± 7 ml/kg/min, P = 0.81) and heart rate at the ventilatory threshold (H = 78 ± 6 vs. C = 78 ± 4% peak heart rate, P = 0.92). During incremental effort exercise in both groups, concentrations of adrenaline and noradrenaline were unchanged through low- and moderate-exercise intensity until reaching a catecholamine threshold (H = 82 ± 4 vs. C = 85 ± 3% peak heart rate, P = 0.86) after which levels of both molecules rose rapidly. In patients with mild non-obstructive HCM, plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold but rise rapidly at higher intensities of exercise. Routine cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM.

Endurance exercise training attenuates natriuretic peptide release during maximal effort exercise: biochemical correlates of the "athlete's heart".

Endurance exercise training (ET) stimulates eccentric left ventricular hypertrophy (LVH) with left atrial dilation. To date, the biochemical correlates of exercise-induced cardiac remodeling (EICR) remain incompletely understood. Collegiate male rowers (n = 9) were studied with echocardiography and maximal-effort cardiopulmonary exercise testing (MECPET) before and after 90 days of ET intensification. Midregional proatrial natriuretic peptide (MR-proANP), NH2-terminal pro B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T were measured at rest, peak MECPET, and 60 min post-MECPET at both study time points. Endurance exercise training resulted in eccentric LVH (LV mass = 102 ± 8 vs. 110 ± 11 g/m2, P = 0.001; relative wall thickness = 0.36 ± 0.04 vs. 0.37 ± 0.04, P = 0.103), left atrial dilation (74 ± 18 vs. 84 ± 15 ml, P < 0.001), and increased exercise capacity (peak V̇o2 = 53.0 ± 5.9 vs. 67.3 ± 8.2 ml·kg-1·min-1, P < 0.001). Left ventricular remodeling was characterized by an ~7% increase in LV wall thickness but only a 3% increase in LV chamber radius. The magnitude of natriuretic peptide release, examined as percent change from rest to peak exercise, was significantly lower for both MR-proANP (115 [95,127]% vs. 78 [59,87]%, P = 0.04) and NT-proBNP (46 [31,70]% vs. 27 [25,37]%, P = 0.02) after ET. Rowing-based ET and corollary EICR appear to result in an attenuated natriuretic peptide response to maximal effort exercise. This may occur as a function of decreased cardiac wall stress after ET as seen by disproportionally higher ventricular wall thickening compared with chamber dilation.NEW & NOTEWORTHY Using longitudinal pre- and postendurance training natriuretic peptide measurements, we demonstrate that the development of exercise-induced cardiac remodeling results in an attenuated natriuretic peptide response to acute bouts of maximal intensity exercise. Exercise-induced cardiac remodeling was associated with a disproportionally higher ventricular wall thickening compared with chamber dilation, a pattern that reduces cardiac wall stress. These observations advance our understanding of both the structural and biochemical adaptations that underlie the cardiovascular response to endurance training.

Structure and Composition Define Immunorecognition of Nucleic Acid Nanoparticles.

Nucleic acid nanoparticles (NANPs) have evolved as a new class of therapeutics with the potential to detect and treat diseases. Despite tremendous advancements in NANP development, their immunotoxicity, one of the major impediments in clinical translation of traditional therapeutic nucleic acids (TNAs), has never been fully characterized. Here, we describe the first systematically studied immunological recognition of 25 representative RNA and DNA NANPs selected to have different design principles and physicochemical properties. We discover that, unlike traditional TNAs, NANPs used without a delivery carrier are immunoquiescent. We show that interferons (IFNs) are the key cytokines triggered by NANPs after their internalization by phagocytic cells, which agrees with predictions based on the experiences with TNAs. However, in addition to type I IFNs, type III IFNs also serve as reliable biomarkers of NANPs, which is usually not characteristic of TNAs. We show that overall immunostimulation relies on NANP shapes, connectivities, and compositions. We demonstrate that, like with traditional TNAs, plasmacytoid dendritic cells serve as the primary interferon producers among all peripheral blood mononuclear cells treated with NANPs, and scavenger receptor-mediated uptake and endosomal Toll-like receptor signaling are essential for NANP immunorecognition. The TLR involvement, however, is different from that expected for traditional TNA recognition. Based on these results, we suggest that NANP technology may serve as a prototype of auxiliary molecular language for communication with the immune system and the modulation of immune responses.

Dengue fever as a cause of perimyocarditis and low-pressure cardiac tamponade.

We describe a case of dengue shock syndrome, perimyocarditis, and low-pressure cardiac tamponade following a trip to the Caribbean. The case was managed in the critical care unit and 6 weeks after discharge the patient was asymptomatic with a normal ejection fraction. Dengue fever presenting as cardiac tamponade is exceedingly rare and emphasizes the importance of taking a thorough travel history as well as being aware of atypical manifestations of rare diseases to make a correct diagnosis.