Search

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.

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.

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

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

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

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.

Background— Pulmonary vascular (PV) distensibility, defined as the percent increase in pulmonary vessel diameter per mm Hg increase in pressure, permits the pulmonary vessels to increase in size to accommodate increased blood flow. We hypothesized that PV distensibility is abnormally low in patients with heart failure (HF) and serves as an important determinant of right ventricular performance and exercise capacity. Methods and Results— Patients with HF with preserved ejection fraction (n=48), HF with reduced ejection fraction (n=55), pulmonary arterial hypertension without left heart failure (n=18), and control subjects (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PV distensibility was derived from 1257 matched measurements (mean±SD, 8.3±2.8 per subject) of pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output. PV distensibility was lowest in the pulmonary arterial hypertension group (0.40±0.24% per mm Hg) and intermediate in the HF with preserved ejection fraction and HF with reduced ejection fraction groups (0.92±0.39 and 0.84±0.33% per mm Hg, respectively) compared to the control group (1.39±0.32% per mm Hg, P P 2. PV distensibility also predicted cardiovascular mortality independent of peak VO 2 in HF patients (n=103; Cox hazard ratio, 0.30; 95% confidence interval, 0.10–0.93; P =0.036). In a subset of patients with HF with reduced ejection fraction (n=26), 12 weeks of treatment with the pulmonary vasodilator sildenafil or placebo led to a 24.6% increase in PV distensibility ( P =0.015) in the sildenafil group only. Conclusions— PV distensibility is reduced in patients with HF and pulmonary arterial hypertension and is closely related to RV systolic function during exercise, maximal exercise capacity, and survival. Furthermore, PV distensibility is modifiable with selective pulmonary vasodilator therapy and may represent an important target for therapy in selected HF patients with pulmonary hypertension. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00309790.

There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed.

Background: Accumulating case reports have described tendon rupture in men who use anabolic-androgenic steroids (AAS). However, no controlled study has assessed the history of tendon rupture in a large cohort of AAS users and comparison nonusers. Hypothesis: Men reporting long-term AAS abuse would report an elevated lifetime incidence of tendon rupture compared with non–AAS-using bodybuilders. Study Design: Cohort study; Level of evidence, 3. Methods: Medical histories were obtained from 142 experienced male bodybuilders aged 35 to 55 years recruited in the course of 2 studies. Of these men, 88 reported at least 2 years of cumulative lifetime AAS use, and 54 reported no history of AAS use. In men reporting a history of tendon rupture, the circumstances of the injury, prodromal symptoms, concomitant drug or alcohol use, and details of current and lifetime AAS use (if applicable) were recorded. Surgical records were obtained for most participants. Results: Nineteen (22%) of the AAS users, but only 3 (6%) of the nonusers, reported at least 1 lifetime tendon rupture. The hazard ratio for a first ruptured tendon in AAS users versus nonusers was 9.0 (95% CI, 2.5-32.3; P < .001). Several men reported 2 or more independent lifetime tendon ruptures. Interestingly, upper-body tendon ruptures occurred exclusively in the AAS group (15 [17%] AAS users vs 0 nonusers; risk difference, 0.17 [95% CI, 0.09-0.25]; P < .001 [hazard ratio not estimable]), whereas there was no significant difference between users and nonusers in risk for lower-body ruptures (6 [7%] AAS users, 3 [6%] nonusers; hazard ratio, 3.1 [95% CI, 0.7-13.8]; P = .13). Of 31 individual tendon ruptures assessed, only 6 (19%) occurred while weightlifting, with the majority occurring during other sports activities. Eight (26%) ruptures followed prodromal symptoms of nonspecific pain in the region. Virtually all ruptures were treated surgically, with complete or near-complete ultimate restoration of function. Conclusion: AAS abusers, compared with otherwise similar bodybuilders, showed a markedly increased risk of tendon ruptures, particularly upper-body tendon rupture.

Background— Although illicit anabolic-androgenic steroid (AAS) use is widespread, the cardiac effects of long-term AAS use remain inadequately characterized. We compared cardiac parameters in weightlifters reporting long-term AAS use to those in otherwise similar weightlifters without prior AAS exposure. Methods and Results— We performed 2D tissue-Doppler and speckle-tracking echocardiography to assess left ventricular (LV) ejection fraction, LV systolic strain, and conventional indices of diastolic function in long-term AAS users (n=12) and otherwise similar AAS nonusers (n=7). AAS users (median [quartile 1, quartile 3] cumulative lifetime AAS exposure, 468 [169, 520] weeks) closely resembled nonusers in age, prior duration of weightlifting, and current intensity of weight training. LV structural parameters were similar between the two groups; however, AAS users had significantly lower LV ejection fraction (50.6% [48.4, 53.6] versus 59.1% [58.0%, 61.7%]; P =0.003 by two-tailed Wilcoxon rank sum test), longitudinal strain (16.9% [14.0%, 19.0%] versus 21.0% [20.2%, 22.9%]; P =0.004), and radial strain (38.3% [28.5%, 43.7%] versus 50.1% [44.3%, 61.8%]; P =0.02). Ten of the 12 AAS users showed LV ejection fractions below the accepted limit of normal (≥55%). AAS users also demonstrated decreased diastolic function compared to nonusers as evidenced by a markedly lower early peak tissue velocity (7.4 [6.8, 7.9] cm/s versus 9.9 [8.3, 10.5] cm/s; P =0.005) and early-to-late diastolic filling ratio (0.93 [0.88, 1.39] versus 1.80 [1.48, 2.00]; P =0.003). Conclusions— Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.

The international governing body for competitive rowing recently mandated the inclusion of 12-lead ECG during preparticipation screening. We therefore sought to describe normative ECG characteristics and to examine the prevalence of abnormal ECG findings as defined by contemporary athlete ECG interpretation criteria among competitive rowers.Competitive rowers (n=330, 56% male) underwent standard 12-lead ECG at the time of collegiate preparticipation screening. ECGs were analysed quantitatively to develop a sport-specific normative database and then for the presence of abnormalities in accordance with the 2010 European Society of Cardiology (ESC) recommendations and 2013 'Seattle Criteria.'94% of rowers had one or more training-related ECG patterns including sinus bradycardia (51%), sinus arrhythmia (55%), and incomplete right bundle branch block (42%). Males were more likely than females to have isolated voltage criteria for left ventricular hypertrophy (LVH) (51% vs 8%, p0.001) and early repolarisation pattern (76% vs 23%, p0.001). Application of the 2010 ESC criteria, compared to the Seattle criteria, resulted in the classification of a significantly greater number of abnormal ECGs (47% vs 4%; p0.001). The detection of true pathology, accomplished by both interpretation criteria, was confined to a single case of ventricular pre-excitation.Training-related ECG patterns with several gender-based differences are common among competitive rowers. The diagnostic accuracy and down-stream clinical implications of ECG-inclusive preparticipation screening among rowers will be dictated by the choice and future refinement of ECG interpretation criteria.

ObjectivesThis study sought to prospectively study the impact of an appropriate use criteria (AUC)-based educational intervention on transthoracic echocardiography (TTE) ordering among house staff on the inpatient general internal medicine service at an academic medical center.BackgroundAUC for TTE were developed in response to concerns about inappropriate use of TTE. To date, educational interventions based on the AUC to reduce inappropriate use of TTE have not been prospectively studied.MethodsA prospective, time series analysis of an educational intervention was conducted and then compared with TTE ordering on the same medical service during a control period. The intervention consisted of: 1) a lecture to house staff on the 2011 AUC for TTE; 2) a pocket card that applied the AUC to common clinical scenarios; and 3) biweekly e-mail feedback regarding ordering behavior. TTE ordering was tracked over the intervention period on a daily basis and feedback reports were e-mailed at 2-week intervals. The primary outcome was the proportion of inappropriate and appropriate TTE ordered during the intervention period.ResultsOf all TTEs ordered in the control and study periods, 99% and 98%, respectively, were classifiable using the 2011 AUC. During the study period, there was a 26% reduction in the number of TTE ordered per day compared with the number ordered during the control period (2.9 vs. 3.9 TTE, p < 0.001). During the study period, the proportion of inappropriate TTE was significantly lower (5% vs. 13%, p < 0.001) and the proportion of appropriate TTE was significantly higher (93% vs. 84%, p < 0.001).ConclusionsA simple educational intervention produced a significant reduction in the proportion of inappropriate TTE and increased the proportion of appropriate TTE ordered on an inpatient academic medical service. This study provides a practical approach for using the AUC to reduce the number of inappropriate TTE. Further study in other practice environments is warranted.

ObjectivesWe sought to examine the effect of endurance exercise training (EET) on peak systolic left ventricular torsion (LVT) and peak early diastolic untwisting rate (UTR).BackgroundLeft ventricular (LV) structural adaptations to EET have been well characterized. LVT, a recognized marker of LV function in numerous cardiac diseases, has recently been investigated in the setting of exercise. However, longitudinal data characterizing the impact of sustained exercise training on LVT have not been reported.MethodsA prospective, longitudinal study design examined the impact of a 90-day period of training on LV twist mechanics in university male rowers (n = 15, mean age 18.6 ± 0.5 years). Conventional LV structural measurements, LV apical and basal rotation, peak systolic LVT, and peak early diastolic UTR were measured by 2-dimensional and speckle tracking echocardiography before and after the EET study period.ResultsParticipants experienced LV eccentric hypertrophy, characterized by increased LV end-diastolic volume (80.8 ± 8.7 ml/m2 vs. 91.3 ± 8.0 ml/m2, p < 0.001) and LV mass (101.3 ± 11.4 g/m2 vs. 115.7 ± 12.6 g/m2, p = 0.001). There was a significant increase in peak systolic apical rotation (8.9 ± 4.2° vs. 12.7 ± 3.9°, p = 0.002) but no change in basal rotation. This translated into a highly significant increase in peak systolic LVT after EET (14.1 ± 5.0° vs. 18.0 ± 3.6°, p = 0.002). The impact of EET on LV twist mechanics was not confined to ventricular systole, as peak early diastolic UTR (−110.6 ± 41.8°/s vs. −148.0 ± 29.8°/s, p = 0.003) and the percentage of untwisting that occurred by the end of isovolumic relaxation (31.2 ± 12.0% vs. 39.9 ± 14.9%, p = 0.04) increased.ConclusionsParticipation in EET was associated with significant changes in LV twist mechanics characterized by increased apical rotation, LVT, and UTR. These findings suggest that LVT and UTR augmentation may be an important and previously unrecognized component of exercise-induced cardiac remodeling.

Objectives The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro–B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. Background It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. Methods In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP–guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. Results Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP–guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP–guided care as younger subjects. Compared with SOC, NT-proBNP–guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. Conclusions In patients with HF due to LV systolic dysfunction, NT-proBNP–guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390 )

Background Responding to concerns regarding the growth of cardiac testing, the American College of Cardiology Foundation (ACCF) published Appropriate Use Criteria (AUC) for various cardiac imaging modalities. Single modality cardiac imaging appropriateness has been reported but there have been no studies assessing the appropriateness of multiple imaging modalities in an inpatient environment. Methods A retrospective study of the appropriateness of cardiac tests ordered by the inpatient General Internal Medicine (GIM) and Cardiology services at three Canadian academic hospitals was conducted over two one-month periods. Cardiac tests characterized were transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), single-photon emission tomography myocardial perfusion imaging (SPECT), and diagnostic cardiac catheterization. Results Overall, 553 tests were assessed, of which 99.8 % were classifiable by AUC. 91 % of all studies were categorized as appropriate, 4 % may be appropriate and 5 % were rarely appropriate. There were high rates of appropriate use of all modalities by GIM and Cardiology throughout. Significantly more appropriate diagnostic catheterizations were ordered by Cardiology than GIM (93 % vs. 82 %, p =

Background Masters athletes (MAs), people over the age of 35 that participate in competitive sports, are a rapidly growing population that may be uniquely at risk for cardiovascular (CV) disease. The objective of this study was to develop a comprehensive clinical CV profile of MA. Methods An electronic Internet-based survey (survey response rate = 66 %) was used to characterize a community cohort of MAs residing in Eastern Massachusetts, USA. Clinical and lifestyle factors associated with prevalent CV disease were determined using logistic regression. Results Among 591 MAs (66 % men, age = 50 ± 9 years) with 21.3 ± 5.5 years of competitive endurance sport exposure, at least one CV risk factor was present in 64 % including the following: family history of premature atherosclerosis (32 %), prior/current tobacco exposure (23 %), hypertension (12.0 %), and dyslipidemia (7.4 %). There was a 9 % (54/591) prevalence of established CV disease which was accounted for largely by atrial fibrillation (AF) and coronary atherosclerosis (CAD). Prevalent AF was associated with years of exercise exposure [adjusted odds ratio, OR (95 % confidence intervals); OR = 1.10 (1.06, 1.21)] and hypertension [OR = 1.05 (1.01, 1.10)] while CAD was associated with dyslipidemia [OR = 9.09 (2.40, 34.39)] and tobacco use [OR = 1.78 (1.34, 3.10)] but was independent of exercise exposure. Conclusions Among MAs, AF is associated with prior exercise exposure whereas CAD is associated with typical risk factors including dyslipidemia and prior tobacco use. These findings suggest that there are numerous opportunities to improve disease prevention and clinical care in this population.

Ventilatory efficiency, as indicated by the increment in minute ventilation (VE) relative to CO2 production (VCO2), reflects right ventricular-pulmonary vascular (RV-PV) function during exercise. In patients with heart failure (HF), a VE/VCO2 slope greater than 34 purports a poor prognosis. Less is

Background The 2007 Appropriate Use Criteria (AUC) for echocardiography was revised in 2011 to cover a wider range of scenarios of use. Previous studies of the 2007 AUC found a relatively large number of unclassified transthoracic echocardiograms (TTEs). Methods We conducted a retrospective chart review comparing TTE usage in three clinical environments: academic inpatient, academic outpatient, and community outpatient. We assessed the TTE ordering behavior using both the 2007 and 2011 AUC. Results We reviewed 150 consecutive TTEs performed in 2011 in each of the three practice settings (total 450). Using the 2007 AUC, 347 TTEs (77%) were classifiable, and, using the 2011 AUC, 441 TTEs (98%) were classifiable ( P P P = .14), and the percentage of uncertain TTEs was 0% and 7% ( P P = .004). Conclusions The 2011 AUC classified a significantly greater proportion of TTEs than the 2007 AUC across a variety of practice settings. The rate of appropriate TTEs was lower using the 2011 AUC, and the appropriateness ratings varied by clinical setting. These findings suggest that the expanded AUC offer an opportunity for improvement in TTE usage.