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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.

Significance Unlike other great apes, humans evolved multisystem capabilities for moderate-intensity EPA, but it is unknown if selection acted similarly on the heart. We present data from a sample of humans, chimpanzees, and gorillas showing that the human (LV) evolved numerous features that help to augment stroke volume (SV), enabling moderate-intensity EPA. We also show that phenotypic plasticity of the human LV trades off pressure adaptations for volume capabilities, becoming more similar to a chimpanzee-like heart in response to physical inactivity or chronic pressure loading. Consequently, the derived human heart appears partly dependent upon moderate EPA and its absence, in combination with a highly processed diet, likely contributes to the modern epidemic of hypertensive heart disease., Chimpanzees and gorillas, when not inactive, engage primarily in short bursts of resistance physical activity (RPA), such as climbing and fighting, that creates pressure stress on the cardiovascular system. In contrast, to initially hunt and gather and later to farm, it is thought that preindustrial human survival was dependent on lifelong moderate-intensity endurance physical activity (EPA), which creates a cardiovascular volume stress. Although derived musculoskeletal and thermoregulatory adaptations for EPA in humans have been documented, it is unknown if selection acted similarly on the heart. To test this hypothesis, we compared left ventricular (LV) structure and function across semiwild sanctuary chimpanzees, gorillas, and a sample of humans exposed to markedly different physical activity patterns. We show the human LV possesses derived features that help augment cardiac output (CO) thereby enabling EPA. However, the human LV also demonstrates phenotypic plasticity and, hence, variability, across a wide range of habitual physical activity. We show that the human LV’s propensity to remodel differentially in response to chronic pressure or volume stimuli associated with intense RPA and EPA as well as physical inactivity represents an evolutionary trade-off with potential implications for contemporary cardiovascular health. Specifically, the human LV trades off pressure adaptations for volume capabilities and converges on a chimpanzee-like phenotype in response to physical inactivity or sustained pressure loading. Consequently, the derived LV and lifelong low blood pressure (BP) appear to be partly sustained by regular moderate-intensity EPA whose decline in postindustrial societies likely contributes to the modern epidemic of hypertensive heart disease.

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 Federation 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.

Cardiomyopathies represent a heterogeneous group of heart muscle diseases that are a major cause of morbidity and mortality (Watkins et al., N Engl J Med 364(17):1643–1656, 2011; McMurray, N Engl J Med 362(3):228–238, 2010). Classification schemes for cardiomyopathy have been complex, and efforts have been made to classify the disease states based on myocardial characteristics and etiologies (Maron et al., Circulation 113:1807–1816, 2006). The etiology, diagnosis, and management of dilated cardiomyopathy (DCM), restrictive/infiltrative cardiomyopathy, and hypertrophic cardiomyopathy (HCM) are the subject of this chapter and several features of each form of cardiomyopathy are highlighted in Table 1.

Current clinical practice guidelines for managing Coronary Artery Disease (CAD) account for general cardiovascular risk factors. However, they do not present a framework that considers personalized patient-specific characteristics. Using the electronic health records of 21,460 patients, we created data-driven models for personalized CAD management that significantly improve health outcomes relative to the standard of care. We develop binary classifiers to detect whether a patient will experience an adverse event due to CAD within a 10-year time frame. Combining the patients' medical history and clinical examination results, we achieve 81.5% AUC. For each treatment, we also create a series of regression models that are based on different supervised machine learning algorithms. We are able to estimate with average R squared = 0.801 the time from diagnosis to a potential adverse event (TAE) and gain accurate approximations of the counterfactual treatment effects. Leveraging combinations of these models, we present ML4CAD, a novel personalized prescriptive algorithm. Considering the recommendations of multiple predictive models at once, ML4CAD identifies for every patient the therapy with the best expected outcome using a voting mechanism. We evaluate its performance by measuring the prescription effectiveness and robustness under alternative ground truths. We show that our methodology improves the expected TAE upon the current baseline by 24.11%, increasing it from 4.56 to 5.66 years. The algorithm performs particularly well for the male (24.3% improvement) and Hispanic (58.41% improvement) subpopulations. Finally, we create an interactive interface, providing physicians with an intuitive, accurate, readily implementable, and effective tool.

The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke. We present a novel technique to detect and characterize LAA thrombus in humans using positron emission tomography (PET) of a fibrin-binding radiotracer, [64Cu]FBP8. Initial testing in healthy volunteers (n = 8) revealed that [64Cu]FBP8 was stable to metabolism and was rapidly eliminated with a blood half-life of one hour. Patients with atrial fibrillation (AF) and recent transesophageal echocardiograms (TEEs) of the LAA (positive n = 12, negative n = 12) were studied. PET, integrated with magnetic resonance (PET-MR), of the thorax was performed one hour after [64Cu]FBP8 injection. The maximum standardized uptake value (SUVMax) in the LAA was significantly higher in the TEE positive than negative subjects, median [interquartile range] of 4.0 [3.0–6.0] vs. 2.3 [2.1–2.5]; p < 0.001. A SUVMax threshold of 2.6 correctly identified 12/12 positive TEEs and 10/12 negative ones, yielding an area-under-the-receiver operating characteristic curve of 0.97. The minimum longitudinal magnetic relaxation time (T1Min) in the LAA was significantly shorter in the TEE positive than TEE negative group 970 [780–1080] vs. 1380 [1120–1620], p < 0.05, with some overlap between the groups. Logistic regression using SUVMax and T1Min allowed all TEE positive and negative subjects to be classified with 100% accuracy. A strong correlation was seen between fibrin (SUVMax) and methemoglobin (T1Min) content in the LAA. In conclusion, the detection of LAA thrombus in humans with PET-MR of [64Cu]FBP8 is highly accurate and provides useful information on the biological properties of cardiac thrombus.One Sentence SummaryFirst-in-human fibrin-targeted PET-MR of thrombus

Background: Lower body mass is thought to enhance athletic performance. We explored the relationship between BMI and aerobic fitness in athletic younger and older men and women. Methods: We examined 2224 patients (805 women, 1419 men) ages 17 through 91, referred to the Cardiovascular Performance Program at Massachusetts General Hospital between 2011 and 2019. Cardiorespiratory fitness (CRF; Peak V0 2 ) was assessed and expressed as %- predicted peak V0 2 , using the equation of Jones to adjust for age, height, and weight. Associations were evaluated using linear regression. Results: Mean peak VO 2 was 34.3±14.1 mL/kg/min, and median %-predicted VO 2 was 105%. We observed an inverse association between BMI and CRF in adults over 30 years old ( B = -0.043, p = 3.3x10 -33 for men, B = -0.051, p = 1.6 x 10 -13 for women) (Fig 1a) and men under 30 ( B = -0.025, p = 0.005) (Fig 1b). No linear association was found in younger women ages 17 - 29 ( B = -0.0078, p = 0.38) (Fig 1b). In contrast, a quadratic model disclosed a direct relationship at lower BMI and an inverse relationship at higher BMI (Fig 1c). An examination of high fitness young adults (defined as having %-predicted VO 2 ≥ 120%) demonstrates that fit women have mean BMI’s of 23.15 ± 2.69 (Fig 1d). Conclusion: These data highlight that BMI and fitness in younger aerobically fit women do not follow a simple linear relationship but one that is parabolic in nature. High fitness in young women occurs with highest density in the upper strata of the WHO and NIH-defined range of healthy BMI. These data support a deemphasis of weight loss generally and BMI specifically to enhance aerobic performance in athletic young women.

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

Background There is little understanding of whether a physician's tendency to order an inappropriate cardiac service is associated with the use of other cardiac services and clinical outcomes in their patients with heart failure (HF). Methods and Results We conducted a secondary analysis of 35 Ontario‐based cardiologists who participated in the control arm of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) trial. Transthoracic echocardiograms, ordered during the trial, were classified as rarely appropriate ( rA ), appropriate, or maybe appropriate on the basis of the 2011 appropriate use criteria. Cardiologists were grouped into tertiles of rA transthoracic echocardiogram ordering frequency: low ordering (bottom tertile), n=11; moderate ordering, n=12; or high ordering (top tertile), n=12. The main outcomes were measures of cardiac service use, including cardiology‐related physician visits, tests, and medications. Among 1677 patients with heart failure and an outpatient visit to 1 of 35 cardiologists, we found no significant association between rA transthoracic echocardiogram ordering frequency (by tertile) and cardiac testing use, although patients of cardiologists in the high ordering group had fewer physician visits, on average, than patients seen by low ordering cardiologists. In addition, patients of cardiologists in the highest rA ordering tertile had significantly lower odds of receiving potentially effective interventions, such as β blockers (odds ratio, 0.62; 95% CI , 0.43–0.89), than the low ordering group. Conclusions Although patients of cardiologists who frequently order rA transthoracic echocardiograms do not appear more (or less) likely to have subsequent cardiac tests, these patients have fewer follow‐up visits and lower odds of receiving evidence‐based medications. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02038101.

A Man with Syncope A 63-year-old man who had a history of coronary artery disease and coronary-artery bypass grafting presented with syncope. Echocardiography revealed two masses external to the ri...

Background: The relationship between ordering frequency of rarely appropriate transthoracic echocardiograms on healthcare utilization and patient outcomes in coronary artery disease (CAD) is not known. Our objective was to investigate practice patterns of cardiologists who order a high frequency of low-value transthoracic echocardiograms in patients with CAD and whether practice behavior influences patient outcomes. Methods and Results: A retrospective cohort of outpatient CAD patients was accrued by identifying patients with at least 1 visit to 1 of 35 Ontario-based cardiologists in the EchoWISELY randomized clinical trial (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) control group. The main outcomes of interest were patient-level receipt of diagnostic tests, physician visits, medication prescriptions, and clinical outcomes at 1 year. Our cohort consisted of 3966 patients with CAD (mean [SD] age, 67.8 [12.0] years; 72% men), with an outpatient visit to 1 of 35 eligible cardiologists, stratified into 3 ordering tertiles. Patients of cardiologists in the top ordering tertile of rarely appropriate transthoracic echocardiograms had significantly lower odds of receiving the following services at 1 year compared with patients in the low ordering group: cholesterol assessment (odds ratio [OR], 0.77 [95% CI, 0.65–0.91]); hemoglobin A1c assessment (OR, 0.79 [95% CI, 0.66–0.94]); β-blocker prescription (OR, 0.70 [95% CI, 0.55–0.90]); and aldosterone receptor antagonist prescription (OR, 0.46 [95% CI, 0.22–0.98]). Patients of high ordering cardiologists had greater odds of all-cause mortality at 1 year (OR, 1.54 [95% CI, 1.04–2.28]), although all other outcomes were similar. Conclusions: Patients with CAD seen by cardiologist who ordered a high rate of rarely appropriate transthoracic echocardiograms were less likely to receive potentially high-value screening tests and evidence-based medications than low ordering cardiologists. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02038101.

The management of patients presenting to an emergency department with chest discomfort at low-risk for acute coronary syndrome represents a common clinical challenge. Such patients are often triaged to chest pain units for monitoring and cardiac stress testing for further risk stratification. We conducted a retrospective study of 292 low-risk patients who presented to an emergency department with chest discomfort. We performed physician-adjudicated chart reviews of all patients with positive stress tests to assess downstream testing, subsequent coronary revascularization, and outcomes. Of the 292 patients, 33 (11.3%) had stress tests positive for ischemia, and 12 (4.1%) underwent diagnostic cardiac catheterization. Of the 292 patients, 4 (1.4%) underwent coronary revascularization that may have resulted in a mortality benefit. These data suggest a very low yield of detecting clinically significant coronary disease with stress testing low-risk patients with chest discomfort in emergency department chest pain units.

The appropriate use criteria (AUC) is intended to facilitate rationale of cardiovascular imaging and aid quality improvement efforts [(1,2)][1]. Despite emerging research regarding the role of AUC for transthoracic echocardiography (TTE) in clinical practice, little data exist regarding the

The last few decades have seen substantial growth in the populations of competitive athletes and highly active people (CAHAP). Although vigorous physical exercise is an effective way to reduce the risk of cardiovascular (CV) disease, CAHAP remain susceptible to inherited and acquired CV disease, and may be most at risk for adverse CV outcomes during intense physical activity. Traditionally, multidisciplinary teams comprising athletic trainers, physical therapists, primary care sports medicine physicians, and orthopedic surgeons have provided clinical care for CAHAP. However, there is increasing recognition that a care team including qualified CV specialists optimizes care delivery for CAHAP. In recognition of the increasing demand for CV specialists competent in the care of CAHAP, the American College of Cardiology has recently established a Sports and Exercise Council. An important primary objective of this council is to define the essential skills necessary to practice effective sports cardiology.

Background Appropriate use criteria (AUC) have defined transthoracic echocardiogram (TTE) indications for which there is a clear lack of benefit as rarely appropriate (rA). Objectives This study sought to investigate the impact of an AUC-based educational intervention on outpatient TTE ordering by cardiologists and primary care providers. Methods The authors conducted a prospective, investigator-blinded, multicenter, randomized controlled trial of an AUC-based educational intervention aimed at reducing rA outpatient TTEs. The study was conducted at 8 hospitals across 2 countries. The authors randomized cardiologists and primary care providers to receive either intervention or control (no intervention). The primary outcome measure was the proportion of rA TTEs. Results One hundred and ninety-six physicians were randomized, and 179 were included in the analysis. From December 2014 to April 2016, the authors assessed 14,697 TTEs for appropriateness, of which 99% were classifiable using the 2011 AUC. The mean proportion of rA TTEs was significantly lower in the intervention versus the control group (8.8% vs. 10.1%; odds ratio [OR]: 0.75; 95% confidence interval [CI]: 0.57 to 0.99; p = 0.039). In physicians who ordered, on average, at least 1 TTE per month, there was a significantly lower proportion of rA TTEs in the intervention versus the control group (8.6% vs. 11.1%; OR: 0.76; 95% CI: 0.57 to 0.99; p = 0.047). There was no difference in the TTE ordering volume between the intervention and control groups (mean 77.7 ± 89.3 vs. 85.4 ± 111.4; p = 0.83). Conclusions An educational intervention reduced the number of rA TTEs ordered by attending physicians in a variety of ambulatory care environments. This may prove to be an effective strategy to improve the use of imaging. (A Multi-Centered Feedback and Education Intervention Designed to Reduce Inappropriate Transthoracic Echocardiograms [Echo WISELY]; NCT02038101)

Objective Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown. Methods A retrospective cohort was identified of individuals (N = 65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA, and linear regression, accounting for cardiometabolic factors. Results Median age was 47 years; 22% (n = 14) had NASH. NASH patients had increased median left atrial (LA) volume (28.6 mL/m2 vs. 24.8 mL/m2; P

Objectives To characterize the subgroup of outpatient pediatric patients presenting with chest pain and to determine the effectiveness of published pediatric appropriate use criteria (PAUC) to detect pathology. Study design The Pediatric Appropriate Use of Echocardiography study evaluated the use and yield of transthoracic echocardiography (TTE) before and after PAUC release. Data were reviewed on patients ≤18 years of age who underwent TTE for chest pain. Indications were classified as appropriate (A), may be appropriate (M), and rarely appropriate (R) based on PAUC ratings, and findings were normal, incidental, or abnormal. Results Chest pain was the primary indication in 772 of 4562 outpatient TTE studies (17%) (median age 14 years, IQR 10-16) ordered during the study period: 458 of 772 before (59%) and 314 of 772 after (41 %) the release of PAUC with no change in appropriateness. In A indications (n = 654), 642 (98%) were normal, 5 (1%) had incidental findings, and 7 (1%) were abnormal. A and M detected 100% of all abnormal findings (A: n = 7; M: n = 6; R: n = 0), with an association between ratings and findings ( P .001). There was no association between R rating and any pathology. Conclusions There was no change in ordering patterns with publication of the PAUC. Despite the high rate of TTEs ordered for indications rated A, most studies were normal. Studies that detected pathology were performed for indications rated A or M, but not R. This study supports PAUC as a useful tool in pediatric chest pain evaluation that may subsequently improve the use of TTE.

Objectives To define the role of single or serial measurement of endothelin 1 (ET-1) for prognostication beyond traditional and modern markers of risk in heart failure (HF). Methods In total, 115 patients with chronic systolic HF were followed for 10 months. Clinical assessment and ET-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), highly sensitive troponin I (hsTnI), soluble ST2 (sST2), and galectin 3 were measured at each visit. Results Elevated ET-1 was associated with worse HF, lower right ventricular function, higher pulmonary pressure, and higher left atrial volume index despite similar left ventricular function. ET-1 correlated with angiotensin-converting enzyme inhibitor use. A model containing traditional risk factors, ET-1, NT-proBNP, hsTnI, and sST2 best predicted cardiovascular events, and ET-1 improved reclassification. In an adjusted time-integrated model, percent time spent with ET-1 of 5.90 pg/mL or less was predictive of fewer cardiovascular events (odds ratio, 0.75; 95% confidence interval, 0.62-0.91). ET-1 reduction over time was associated with a lower rate of cardiovascular events compared with increasing or stable ET-1 (24.4% vs 50.0%). Conclusions ET-1 may be a unique predictor of HF prognosis, complementing other biomarkers in a multimarker profile. Serial measurement of ET-1 may provide additional prognostic information.

Cardiovascular imaging plays a central role in the diagnosis and treatment of cardiovascular disease. Recently, increased emphasis has been placed on quality in cardiovascular imaging, and it is becoming a central priority for various stakeholders, including patients, physicians, and payers. The changing health care landscape and associated challenges imposed on cardiac imagers, including reductions in reimbursement and growing need for pre-authorization, have also helped bring quality metrics to the forefront. Continuous quality improvement initiatives provide the framework for the team of physicians, technical staff members, administrators, and other health care professionals to deliver high-quality care. Efforts to improve quality in cardiac imaging have started to form the foundation for numerous research studies in this arena, and although few in number, randomized control trials have begun to emerge. This review highlights quality improvement studies focusing on appropriate use education, reporting, and radiation dose reduction in cardiovascular imaging.

Objective Preliminary data suggest that nonalcoholic fatty liver disease (NAFLD) is associated with early heart failure (HF). However, whether nonalcoholic steatophepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown. Methods We identified a retrospective cohort (N=65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA and linear regression, accounting for cardiometabolic factors. Results Median age was 47 years; 22% (n=14) had NASH. NASH patients had increased median left atrial (LA) volume (28.6mL/m2 vs. 24.8mL/m2, p

Pediatric appropriate use criteria (AUC) were recently published for initial outpatient transthoracic echocardiography (TTE). The purpose of this study was to determine the effect of AUC publication on TTE ordering patterns of pediatric cardiologists. Data were prospectively collected on patients who had initial outpatient TTE ordered before (phase I, April to September 2014) and 3 months after (phase II, January to April 2015) AUC document publication at 6 centers. Site investigators assessed each study's indication and assigned AUC appropriateness as "appropriate" (A), "may be appropriate" (M), "rarely appropriate" (R), or "unclassifiable." One hundred three physicians ordered 4,562 TTEs (2,655 phase I and 1,907 phase II). Overall, there was no statistically significant change in the proportion of A, M, or unclassifiable, but R decreased (12.0% to 9.6%, p = 0.01). There was significant variability among the centers in the percentage of studies for indications rated R (4.9% to 34.8%). There was no significant change in any of the appropriateness ratings at 4 centers, a decrease in R and an increase in A at 1 and a decrease in R and increase in unclassifiable at another. The first pediatric AUC document had only a small impact on physician ordering behavior for initial TTEs, including a small decrease in R. There was a significant variability in appropriateness of studies among centers. These data suggest that active educational interventions are required to substantially improve the appropriate use of pediatric TTE in the outpatient setting.

Purpose Swim training is performed in the prone or supine position and obligates water immersion, factors that may augment cardiac volume loading more than other endurance sports. At present, prospective data defining the cardiac responses to swim training are lacking. We therefore studied myocardial adaptations among competitive swimmers to establish a causal relationship between swim training and left ventricular (LV) remodeling. Methods Collegiate swimmers were studied before and after a 90-d period of training intensification. Transthoracic echocardiography was used to examine LV structural and functional adaptations under resting conditions and during an acute LV afterload challenge generated by isometric handgrip testing (IHGT). A sedentary control population was identically studied with IHGT. Results In response to a discrete period of swim training intensification, athletes (n = 17, 47% female, 19 ± 0.4 yr old) experienced eccentric LV remodeling, characterized by proportionally more chamber dilation than wall thickening, with attendant enhancements of resting LV systolic (LV twist) and diastolic (early and late phase tissue velocities) function. Compared with baseline and controls, athletes posttraining demonstrated greater systolic twist impairment during IHGT. However, training-induced LV dilation coupled with gains in diastolic function offsets this acquired systolic susceptibility to acute afterload, resulting in the relative preservation of stroke volume during IHGT. Conclusion Swim training, a sport characterized by unique cardiac loading conditions, stimulates eccentric LV remodeling with the concomitant augmentation of systolic twist and diastolic relaxation. This volume-mediated cardiac remodeling appears to result in greater systolic susceptibility to acute afterload challenge. Further work is required to establish how training-induced changes in function translate to human performance and whether these are accompanied by physiologic trade-offs with relevance to common forms of heart disease.

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/m(2), P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P

Echocardiography is an important tool in the diagnosis and management of cardiovascular disease. However, there has been concern in recent years regarding the rapid growth of echocardiography utilization. The American College of Cardiology Foundation (ACCF), along with other subspecialty societies, developed Appropriate Use Criteria (AUC) in an effort to promote more effective utilization of diagnostic testing and procedures in cardiovascular medicine, and echocardiography has been a focus of the AUC. AUC are distinct from clinical practice guidelines, as AUC delineate clinical scenarios in which ordering a test or procedure may be considered appropriate or less appropriate. Revised and updated AUC for adult echocardiography were published in 2011. One of the first uses of the AUC for echocardiography was to characterize practice patterns and determine appropriateness rates in clinical practice. Moving beyond a description of ordering patterns in clinical practice, educational intervention studies have been designed which incorporate AUC into the process of educating ordering clinicians. Several studies indicate that it is feasible to teach clinicians about appropriate use and that providing feedback about ordering behavior may improve utilization. The importance and role of feedback in AUC-based educational efforts is supported by the results of these studies. The optimal approach to incorporate AUC into patient selection remains to be determined, and it should be emphasized that clinical judgment remains important and is not to be replaced by criteria. Adherence to AUC and the subsequent impact on clinical outcomes, although difficult to study, is a critical area in need of further investigation.

The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease.

Objective Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD. Design We prospectively evaluated for 12months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography. Results After 12months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4±22.5g/m 2 vs untreated: 72.9±21.3g/m 2 , p=0.89), E/A ratio (GH: 1.21±0.39 vs untreated: 1.08±0.39, p=0.50) or deceleration time (GH: 224.5±60.1ms vs untreated: 260±79.8ms, p=0.32). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p=0.76) classified as having normal diastolic function at follow-up. Conclusions There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population.

The term endurance sport (ES) is broadly used to characterize any exercise that requires maintenance of high cardiac output over extended time. However, the relative amount of isotonic (volume) versus isometric (pressure) cardiac stress varies across ES disciplines. To what degree ES-mediated cardiac remodeling varies, as a function of superimposed isometric stress, is uncertain. The aim of this study was to compare the cardiac remodeling characteristics associated with two common yet physiologically distinct forms of ES.Healthy competitive male long-distance runners (high isotonic, low isometric stress; n = 40) and rowers (high isotonic, high isometric stress; n = 40) were comparatively studied after 3 months of sport-specific exercise training with conventional and speckle-tracking two-dimensional echocardiography.Rowers demonstrated dilated left ventricular (LV) volumes and elevated LV mass (i.e., eccentric LV hypertrophy), whereas runners demonstrated normal LV mass (runners, 88 ± 11 g/m(2); rowers, 108 ± 13 g/m(2); P.001) despite comparatively larger LV volumes (runners, 101 ± 10 mL/m(2); rowers, 89 ± 13 mL/m(2); P.001) consistent with eccentric LV remodeling. Increasing LV mass was associated with increased reliance on early diastolic filling (LV mass vs E'/A' ratio, R = 0.47, P.001) indicating "mass-dependent" diastolic function. Right ventricular dilation of similar magnitude and LV systolic function, as assessed by numerous complementary indices, were similar in both groups.Cardiac adaptations differ significantly as a function of ES discipline. Further work is required to determine the mechanisms for this differential adaptation, to develop definitive ES discipline-specific normative values, and to evaluate the optimal therapeutic use of specific ES disciplines among patients with common cardiovascular diseases.

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.

Background Appropriate use criteria (AUC) represent an important mechanism by which to promote the rational utilization of healthcare resources. No study to date has been conducted assessing the applicability of current AUC to transthoracic echocardiograms (TTEs) performed in a cardiac intensive care unit (CICU). We analyzed 2 years of consecutive TTEs performed in a CICU at a quaternary-care academic medical center, hypothesizing that current AUC may not adequately describe the role of TTE in a modern CICU. Methods Indications for TTEs were independently classified by two investigators in accordance with 2011 AUC. If investigators were unable to assign an AUC classification to a given study, it was deemed to be unclassifiable. Disagreements between investigators were resolved by consensus. Cases in which consensus could not be reached underwent definitive adjudication by a third investigator. Results Of the 826 TTEs, 619 TTEs were classified as appropriate (74.9%, CI 71.8%-77.9%), 12 as uncertain (1.5%, CI 0.75%-2.5%), 21 as rarely appropriate (2.5%, CI 1.6%-3.9%), and 174 were unable to be classified (21.1%, CI 18.3%-24.0%). The most common unclassifiable indication was "initial evaluation of cardiac structure or function after cardiac arrest of unknown etiology" (n = 101). Conclusion Current AUC for TTEs may not adequately address the complexity of clinical cases encountered in the CICU. In our study of 826 consecutive TTEs, 21.1% were unable to be classified, reflecting the difficulty in applying AUC to this unique clinical environment. Further studies are therefore needed to better delineate the appropriateness of TTEs performed in the CICU.

The Echocardiography Appropriate Use Criteria (EAUC) are a set of indications for transthoracic echocardiography (TTE) developed to guide physician decision making around ordering of TTE. In this study, an automated rule-based method for processing “indications” listed within TTE reports and classification into one of the major EAUC categories was developed and validated against a clinician-annotated reference standard. The system performed at a comparable level to trained physicians allowing for the automated classification of more than 30,000 TTE indications from a public database in less than ten minutes. The most common indication for TTE was Valvular assessment closely followed by General. Hypertension/Heart Failure/Cardiomyopathy, Acute, and Cardiac Structure assessment each contributed more than ten percent within this patient population. These results suggest potential for automated approaches for tracking appropriate use of TTE, as well as guide the development of systems for prospectively identifying when TTE use is recommended.

Background Recently published appropriate use criteria (AUC) for initial pediatric outpatient transthoracic echocardiography (TTE) have not yet been evaluated for clinical applicability. Objectives This study sought to determine the appropriateness of TTE as currently performed in pediatric cardiology clinics, diagnostic yield of TTE for various AUC indications, and any gaps in the AUC document. Methods Data were prospectively collected from patients undergoing initial outpatient TTE in 6 centers. TTE indications (appropriate [A], may be appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or abnormal) were recorded. Results Of the 2,655 studies ordered by 102 physicians, indications rated A, M, and R were found in 1,876 (71%), 316 (12%), and 319 studies (12%), respectively, and 144 studies (5%) were unclassifiable. Twenty-four of 113 indications (21%) were not used. Innocent murmur and syncope or palpitations with no other indications of cardiovascular disease, a benign family history, and normal electrocardiogram accounted for 75% of indications rated R. Pathologic murmur had the highest yield of abnormal findings (40%). Odds of an abnormal finding in an A or M TTE were 6 times that of R (95% confidence interval [CI]: [2.8 to 12.8]). Abnormal findings were more common in patients 10 years of age (odds ratio: 6.4; 95% CI: 4.7 to 8.7). Age was a significant predictor of an abnormal finding after adjusting for indication and site (p Conclusions Most TTEs ordered in pediatric cardiology clinics were for indications rated A. AUC ratings successfully stratified indications based on the yield of abnormal findings. This study identified differences in the yield of TTE based on patient age and most common indications rated R. These findings should inform quality improvement efforts and future revisions of the AUC document.

Background Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. Aims The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. Methods In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. Conclusions The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101).

Exercise-induced cardiac remodeling is a complex process by which the cardinal hemodynamic stresses of pressure and volume lead to a host of structural or functional adaptations. In aggregate, the constellation of changes that accompany this process serve to facilitate athletic performance by minimizing the cardiac work inherent in athletic activity. Although several key determinants of athletic cardiac adaptation have been described, observed variability across athlete cohorts remains an incompletely understood area. Ongoing and future work are required to further understand this process and ultimately to determine where the boundary lies between adaptive physiology and maladaptive disease.

Highly sensitive troponin (hsTn) assays may predict cardiovascular (CV) events and left ventricular (LV) remodeling in patients with heart failure (HF). In this study, 99 subjects with LV systolic dysfunction (LVSD) were followed 10 ± 3 months with serial measurement of hsTnI by a novel method. hsTnI was detectable in all subjects and was above the 99th percentile of a normal population in 56.7 %. Supramedian baseline hsTnI concentration was associated with higher-risk clinical features and shorter time-to-first event (p = 0.008). Across serial measurements, more time spent ≤ 10.9 pg/mL was associated with a lower CV event rate after adjustment (odds ratio (OR) = 0.81; p = 0.008); rising hsTnI also predicted progressive LV remodeling. In conclusion, hsTnI detected significant myocardial necrosis in a majority of patients with chronic HF due to LVSD and when measured serially, provided independent risk information for poor CV outcomes and deleterious LV remodeling.

Background Galectin-3 is a prognostic heart failure biomarker associated with aldosterone-induced myocardial fibrosis; mineralocorticoid receptor antagonists (MRAs) may reduce such fibrosis. We sought to examine outcomes of patients with heart failure with reduced ejection fraction (HFrEF) as a function of galectin-3 and MRA therapy. Methods A total of 151 patients with chronic HFrEF were categorized by baseline galectin-3 and subsequent MRA therapy trends with regard to cardiovascular (CV) events, left ventricular remodeling, safety, and quality of life, over a mean of 10 months. Results Although galectin-3 >20 ng/mL was associated with doubling in adjusted risk for CV events, regardless of MRA treatment, there was no difference in CV event rates with regard to MRA use patterns, independent of galectin-3 concentrations. Specifically, in patients with elevated galectin-3 treated with intensified MRA therapy, a significant difference was not detected in CV event rates ( P = .79) or the cumulative number of such events ( P = .76). Adjusted analysis revealed no difference in time to first CV event if MRA was added/intensified in those with elevated galectin-3 (hazard ratio 0.99, 95% CI 0.97-1.02, P = .74); similarly, cumulative MRA dose was not a specific predictor of benefit. In those with elevated galectin-3, MRA therapy did not affect left ventricular remodeling indices or quality of life at follow-up; these patients had the highest rates of treatment-related adverse events with intensified MRA use. Regardless of MRA use, elevated galectin-3 was associated with more significant renal dysfunction. Conclusions Among patients with chronic HFrEF and elevated galectin-3 concentrations, we found no specific benefit from addition or intensification of MRA therapy.

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic–androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Out-patient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiological testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes [estimated difference, 95% confidence interval (CI) = 2.3 (0.1, 4.5) ml; P = 0.042] and lower serum testosterone levels [estimated difference: 95% CI = 131 (25, 227) dl; P = 0.009], with five users showing testosterone levels below 200 ng/dl despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF sexual desire subscale [estimated difference: 95% CI = 2.4 (1.3, 3.4) points on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus untreated former users, seven (29%) had experienced major depressive episodes during AAS withdrawal; four of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic–androgenic steroid misusers, anabolic–androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged and associated with substantial morbidity.