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Marathon running commonly causes a transient elevation of creatine kinase and cardiac troponin I (cTnI). The use of statins before marathon running exacerbates the release of creatine kinase from skeletal muscle, but the effect of statin use on exercise-induced cTnI release is unknown. We therefore measured cTnI concentrations in statin-using (n = 30) and nonstatin-using (n = 41) runners who participated in the 2011 Boston Marathon. All runners provided venous blood samples the day before, within an hour of finishing, and 24 hours after the marathon. cTnI was assessed at each time point via both a contemporary cTnI and high-sensitivity cTnI (hsTnI) assay. Before the marathon, cTnI was detectable in 99% of runners with the use of the hsTnI assay. All participants completed the marathon (finish time: 4:04:09 ± 0:41:10), and none had symptoms of an acute coronary syndrome. cTnI increased in all runners (p <0.001) immediately after the marathon, and half (hsTnI = 54% vs contemporary cTnI = 47%) exceeded the diagnostic cut-point for an acute myocardial infarction. Statin use did not affect the magnitude of cTnI release (group*time p = 0.47) or the incidence of runners with cTnI elevation greater than the diagnostic cut-point for myocardial infarction (57% vs 51%, p = 0.65). In addition, there was no significant association between statin potency and cTnI release (r = 0.09, p = 0.65). In conclusion, marathon-induced cTnI increases are not altered by statin use., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In recent years, athletic participation has more than doubled in all major demographic groups, while simultaneously, children and adults with established heart disease desire participation in sports and exercise. Despite conferring favorable long-term effects on well-being and survival, exercise can be associated with risk of adverse events in the short term. Complex individual cardiovascular (CV) demands and adaptations imposed by exercise present distinct challenges to the cardiologist asked to evaluate athletes. Here, we describe the evolution of sports and exercise cardiology as a unique discipline within the continuum of CV specialties, provide the rationale for tailoring of CV care to athletes and exercising individuals, define the role of the CV specialist within the athlete care team, and lay the foundation for the development of Sports and Exercise Cardiology in the United States. In 2011, the American College of Cardiology launched the Section of Sports and Exercise Cardiology. Membership has grown from 150 to over 4,000 members in just 2 short years, indicating marked interest from the CV community to advance the integration of sports and exercise cardiology into mainstream CV care. Although the current athlete CV care model has distinct limitations, here, we have outlined a new paradigm of care for the American athlete and exercising individual. By practicing and promoting this new paradigm, we believe we will enhance the CV care of athletes of all ages, and serve the greater athletic community and our nation as a whole, by allowing safest participation in sports and physical activity for all individuals who seek this lifestyle., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are intracellular mediators of adaptive processes, including muscle hypertrophy, contractile force generation, and inflammation. During basal conditions and tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise on plasma concentrations of c-miRNAs remains incompletely characterized. We hypothesized that specific c-miRNAs are differentially upregulated following prolonged aerobic exercise. To test this hypothesis, we measured concentrations of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR-208a), and the vascular endothelium (miR-126), as well as those important in inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest, immediately after a marathon (42-km foot race), and 24 h after the race. In addition, we compared c-miRNA profiles to those of conventional protein biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and systemic inflammation. Candidate c-miRNAs increased immediately after the marathon and declined to prerace levels or lower after 24 h of race completion. However, the magnitude of change for each c-miRNA differed, even when originating from the same tissue type. In contrast, traditional biomarkers increased after exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond differentially to prolonged exercise, suggesting the existence of specific mechanisms of c-miRNA release and clearance not fully explained by generalized cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal fashion from corollary conventional tissue-specific biomarkers, emphasizing the potential of c-miRNAs as unique, real-time markers of exercise-induced tissue adaptation.

Myocardial remodeling is pivotal in the progression and complication of chronic heart failure (HF). We assessed serial measurement of five biomarkers with biologic links to remodeling (biglycan, secreted frizzled-related protein 3, endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in 142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were most associated with events; in fully adjusted models, lower IGFBP7 concentrations across visits independently predicted fewer events (odds ratio [OR] = 0.83; 95 % confidence interval [CI] = 0.73-0.95, p = 0.01). Subjects with rising mimecan had greater decrease in left ventricular end diastolic (p = 0.07) and systolic (p = 0.01) volumes, greater increase in ejection fraction (p = 0.02), and had lowest event rates. Statistical models suggested several HF medications might lead to changes in both IGFBP7 and mimecan values. The results suggest serial measurement of IGFBP7 provides prognostic information, while changes in mimecan provide unique information regarding myocardial remodeling.

Objectives: The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis., Setting: field study at Boston Marathon., Participants: 42 qualifiers (mean age±SD: 46±13 years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12 years, n=21 women)., Outcomes: We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10 years Framingham risk, central arterial stiffness and SBP and cIMT., Results: Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r≥0.41; p<0.01) and Framingham risk score (all r≥0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75 bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model., Conclusions: Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors.

Objectives: The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM)., Background: Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging., Methods: In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement., Results: There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. -5% [-11% to -0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% ± 26% with placebo vs. -23% ± 45% with losartan; p = 0.03)., Conclusions: This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF., Methods and Results: A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels., Conclusion: In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels.

Sudden cardiac death in young athletes is rare but tragic. The cardiology community is faced with the challenge of providing a sensible strategy for the prevention of SCD while simultaneously reaffirming that the benefits of regular exercise far outweigh potential risks. At present, there is a broad range of screening recommendations dependent upon country, sporting discipline, and competition level. While much recent debate has focused on the efficacy of screening with electrocardiography, a number of sporting bodies also mandate the inclusion of exercise testing and echocardiography in screening protocols. Cardiac magnetic resonance imaging, coronary calcium scoring and computed tomography coronary angiography have also been promoted as potentially valuable screening tools for competitive athletes. This review will examine the controversial topic of utilizing cardiac imaging for athlete pre-participation screening. Specifically, the limitations of screening for relatively rare disorders using imaging tools with uncertain or imperfect accuracy will be addressed. Current evidence suggests that the accuracy of all cardiac imaging modalities is insufficient to justify their use as primary screening modalities in athletes. Atypical findings such as marked cardiac dilation, reduced deformation, or small patches of delayed gadolinium enhancement may be commonly encountered in well-trained athletes, but, at present, the prognostic significance of such findings is unknown. Resulting uncertainty for the clinician and athlete has the potential for psychological stress, further testing, and unnecessary exclusions from competition. However, these concerns must not be confused with the extremely useful applications of cardiac imaging for the assessment of athletes with symptoms, an abnormal electrocardiogram or a positive family history. As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known., Methods and Results: We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; P<0.001) and diastolic BP (64±8 mm Hg versus 66±10 mm Hg; P<0.001). At the postseason assessment, the majority of athletes met criteria for Joint National Commission (seventh report) prehypertension (53 of 113, 47%) or stage 1 hypertension (16 of 113, 14%). Among measured characteristics, lineman field position, intraseason weight gain, and family history of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001)., Conclusions: Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.

Cross-kingdom delivery of specific microRNAs to recipient organisms via food ingestion has been reported recently. However, it is unclear if such delivery of microRNAs occurs frequently in animal organisms after typical dietary intake. We found substantial levels of specific microRNAs in diets commonly consumed orally by humans, mice, and honey bees. Yet, after ingestion of fruit replete with plant microRNAs (MIR156a, MIR159a, and MIR169a), a cohort of healthy athletes did not carry detectable plasma levels of those molecules. Similarly, despite consumption of a diet with animal fat replete in endogenous miR-21, negligible expression of miR-21 in plasma or organ tissue was observed in miR-21 -/- recipient mice. Correspondingly, when fed vegetarian diets containing the above plant microRNAs, wild-type recipient mice expressed insignificant levels of these microRNAs. Finally, despite oral uptake of pollen containing these plant microRNAs, negligible delivery of these molecules was observed in recipient honeybees. Therefore, we conclude that horizontal delivery of microRNAs via typical dietary ingestion is neither a robust nor a frequent mechanism to maintain steady-state microRNA levels in a variety of model animal organisms, thus defining the biological limits of these molecules in vivo.

Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible., (© 2012 Wiley Periodicals, Inc.)

Background: In patients with left ventricular systolic dysfunction (LVSD), the rate at which oxygen uptake (VO2) increases on initiation of exercise is inadequate to match metabolic demands. To gain mechanistic insights into delayed VO2 kinetics in LVSD, we simultaneously assessed hemodynamic measurements, ventilatory parameters, and peripheral oxygen usage during exercise., Methods and Results: Forty-two patients with symptomatic LVSD (age, 59±2 years [mean±SEM]; LV ejection fraction, 30±1%) and 17 controls (LV ejection fraction, 68±1%) underwent maximum upright cycle ergometry cardiopulmonary exercise testing. Hemodynamic monitoring and first-pass radionuclide ventriculography were performed at rest and during exercise. VO2 kinetics were quantified by mean response time (MRT), which was significantly longer in patients with LVSD compared with controls (64±3 versus 45±5 s; P=0.004). In LVSD patients, MRT was associated with higher biventricular filling pressures and reduced cardiac output during early exercise. LVSD patients with MRT ≥60 s, compared with LVSD subjects with MRT <60 s, demonstrated greater impairment in right ventricular-pulmonary vascular function during exercise as evidenced by lower right ventricular ejection fraction (35±2 versus 45±2%; P=0.03), steeper increment in transpulmonary gradient relative to cardiac output (3.7 versus 2.2 mm Hg/L; P<0.001), and increased ventilatory dead-space fraction (17±1 versus 12±2%; P=0.03). In contrast, MRT was not associated with LV ejection fraction (rest, exercise), PaO2, hemoglobin, or resting pulmonary function test results., Conclusions: Delayed oxygen uptake on initiation of exercise (ie, MRT ≥60 s) in LVSD is closely related to impaired right ventricular-pulmonary vascular function and may represent an important surrogate for inability to augment RV performance during physical activity in patients with heart failure.

Aims: We sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function., Methods and Results: Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) ↑LV end-diastolic volume index = 1.43, 95% confidence interval (CI) 1.10-1.86, P = 0.007; HR ↑LV end-systolic volume index = 1.54, 95% CI 1.10-1.91, P = 0.01; HR ↓LV ejection fraction (LVEF) = 1.53, 905% CI 1.12-1.89, P = 0.02]. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity., Conclusion: NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC.

Cardiac channelopathies are potentially lethal inherited arrhythmia syndromes and an important cause of sudden cardiac death (SCD) in young athletes. Other cardiac rhythm and conduction disturbances also may indicate the presence of an underlying cardiac disorder. The 12-lead ECG is utilised as both a screening and a diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of a pathological cardiac disease. This article describes ECG findings present in primary electrical diseases afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

Electrocardiographic changes in athletes are common and usually reflect benign structural and electrical remodelling of the heart as a physiological adaptation to regular and sustained physical training (athlete's heart). The ability to identify an abnormality on the 12-lead ECG, suggestive of underlying cardiac disease associated with sudden cardiac death (SCD), is based on a sound working knowledge of the normal ECG characteristics within the athletic population. This document will assist physicians in identifying normal ECG patterns commonly found in athletes. The ECG findings presented as normal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and collectively are the leading cause of sudden cardiac death (SCD) in young athletes. The 12-lead ECG is utilised as both a screening and diagnostic tool for detecting conditions associated with SCD. Fundamental to the appropriate evaluation of athletes undergoing ECG is an understanding of the ECG findings that may indicate the presence of an underlying pathological cardiac disorder. This article describes ECG findings present in cardiomyopathies afflicting young athletes and outlines appropriate steps for further evaluation of these ECG abnormalities. The ECG findings defined as abnormal in athletes were established by an international consensus panel of experts in sports cardiology and sports medicine.

The likelihood of success of conservative management of obstructive hypertrophic cardiomyopathy (HC) and the predictors of failure of conservative therapy are not known. We therefore evaluated the efficacy of an algorithm for the management of symptoms and predictors of failed conservative therapy in 249 consecutive symptomatic patients with obstructive HC referred to a dedicated HC program for management in general or for septal reduction therapy (SRT) in particular. There was considerable practice variation in the extent to which conservative therapy was optimized before referral for SRT. Over 3.7 ± 2.9-year follow-up, symptoms resolved with addition of or increase in dosage of a β blocker, calcium channel blocker, or disopyramide in 16%, 10%, and 10% of patients, respectively. Pacing with short atrioventricular delay controlled symptoms in 4 of 9 patients. In 63% of patients, conservative measures failed to control symptoms. Multivariate predictors of failure of conservative therapy were presence of New York Heart Association class III or IV symptoms (hazard ratio 2.0, 95% confidence interval 1.4 to 2.9, p = 0.001) and greater septal wall thickness (hazard ratio 1.06, 95% confidence interval 1.02 to 1.10, p = 0.003) at presentation. At time of presentation, 93 patients (37%) were already on optimal therapy and were referred for SRT. Of the remaining 156 patients who did not require immediate SRT, 93 (60%) were free from a recommendation for SRT at the end of the follow-up period. In conclusion, in symptomatic patients with obstructive HC, conservative therapy is successful in >1/3 of referred patients at 3.7-year follow-up, obviating SRT in these patients. Clinicians in programs offering SRT should optimize conservative therapy before recommending SRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Left ventricular (LV) rotation occurs due to contraction of obliquely oriented myocardial fibres. Left ventricular twist (LVT) results from rotation of the apex and base in opposite directions. Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood. Isometric handgrip testing (IHGT), a well-established laboratory-based technique to increase LV afterload, was performed for 3 min at 40% maximum force generation in healthy human subjects (n = 18, mean age 29.7 ± 2.7 years). Speckle-tracking echocardiography was used to measure LV volumes, LV apical and basal rotation, peak systolic LVT and peak early diastolic untwisting rate (UTR) at rest and at peak IHGT. IHGT led to significant increase in systemic blood pressure (systolic, 120.6 ± 9.7 vs. 155.6 ± 14.5 mmHg, P < 0.001; diastolic, 67.5 ± 6.4 vs. 94.1 ± 21.1 mmHg, P < 0.001) and LV end-systolic volume (44.2 ± 7.8 vs. 50.5 ± 10.8 ml, P = 0.005), as well as a significant increase in heart rate (62.8 ± 11.7 vs. 84.7 ± 13.8 beats min−1; P < 0.001). IHGT produced a significant acute reduction in LV stroke volume (63.9 ± 12.0 vs. 49.4 ± 7.8 ml, P < 0.001). In this setting, there was a significant decrease in peak systolic apical rotation (11.9 ± 3.0 vs. 8.6 ± 2.2 deg, P < 0.001) and a resultant 25% decrease in peak systolic LVT (16.6 ± 2.8 vs. 12.5 ± 2.8 deg, P < 0.001). The magnitude of peak early diastolic UTR did not change (−114.5 ± 26.4 vs. −110.6 ± 39.8 deg s−1, P = 0.71). Peak systolic apical rotation and LVT decrease during IHGT in healthy humans. This impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload.

Background: Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study., Methods and Results: A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP-guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP-guided care for elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10)., Conclusions: Natriuretic peptide-guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (ClinicalTrials.Gov #00351390)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The reduction in the size of full-capability echocardiographic machines facilitates "out-of-hospital" transthoracic echocardiography (TTE). Data documenting the feasibility, yield, and logistical considerations of out-of-hospital TTE for preparticipation evaluation of athletes are sparse., Methods: A multiyear study was conducted to examine the role of 12-lead electrocardiography for athlete screening in which TTE was used to document or exclude underlying structural heart disease. Using a commercially available portable transthoracic echocardiographic system, the rate of technically adequate imaging, diagnostic yield, and the time required for the completion of TTE (including setup, performance, and interpretation) were examined. TTE was performed in university medical offices and at "out-of-office" athletic facilities. Measurements were recorded during each year of the study to determine the impact of targeted attempts to improve efficiency., Results: Four hundred sixty-seven of 510 participants had transthoracic echocardiographic images that were technically adequate for complete interpretation (imaging success rate, 92%). Echocardiographic evidence of physiologic, exercise-induced cardiac remodeling was observed in 110 of 510 (22%). Cardiac abnormalities with relevance to sports participation risk were detected in 11 of 508 participants (2.2%). Over 3 years, the average time for the completion of TTE (including setup, imaging, and interpretation) decreased (year 1, 17.4 ± 3 min; year 2, 14.0 ± 2.1 min; year 3, 11.0 ± 1.8 min; P < .001). This was driven by a significant decrease in the time required for TTE at out-of-office athletic facilities., Conclusions: Community-based TTE in athletes is feasible and is associated with a high rate of technically adequate imaging. Importantly, there appears to be a significant learning curve associated with out-of-hospital TTE., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The clinical evaluation of athletes during symptom evaluation or pre-participation screening often involves interpretation of the 12-lead electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of underlying cardiovascular disease from benign findings caused by exercise-induced cardiac adaptations can be challenging, and recent clinical guidelines have been created for this purpose. One of the most common ECG findings in athletes is the early repolarization pattern (ERP), characterized by diffuse J-point elevation and concave ST-segment elevation, and long regarded as a normal variant. However, recently published data suggest that the ERP may be a marker of increased risk for sudden cardiac death (SCD) in the general population. The observation that the ERP can indicate increased SCD risk has important implications for the clinician charged with the care of athletes. This review will describe the evolving understanding of the ERP and will explore the relevance of the ERP for the care of athletes.

Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Approximately 2 million people participate in long-distance running races in the United States annually. Reports of race-related cardiac arrests have generated concern about the safety of this activity., Methods: We assessed the incidence and outcomes of cardiac arrest associated with marathon and half-marathon races in the United States from January 1, 2000, to May 31, 2010. We determined the clinical characteristics of the arrests by interviewing survivors and the next of kin of nonsurvivors, reviewing medical records, and analyzing postmortem data., Results: Of 10.9 million runners, 59 (mean [±SD] age, 42-13 years; 51 men) had cardiac arrest (incidence rate, 0.54 per 100,000 participants; 95% confidence interval [CI], 0.41 to 0.70). Cardiovascular disease accounted for the majority of cardiac arrests. The incidence rate was significantly higher during marathons (1.01 per 100,000; 95% CI, 0.72 to 1.38) than during half-marathons (0.27; 95% CI, 0.17 to 0.43) and among men (0.90 per 100,000; 95% CI, 0.67 to 1.18) than among women (0.16; 95% CI, 0.07 to 0.31). Male marathon runners, the highest-risk group, had an increased incidence of cardiac arrest during the latter half of the study decade (2000-2004, 0.71 per 100,000 [95% CI, 0.31 to 1.40]; 2005-2010, 2.03 per 100,000 [95% CI, 1.33 to 2.98]; P=0.01). Of the 59 cases of cardiac arrest, 42 (71%) were fatal (incidence, 0.39 per 100,000; 95% CI, 0.28 to 0.52). Among the 31 cases with complete clinical data, initiation of bystander-administered cardiopulmonary resuscitation and an underlying diagnosis other than hypertrophic cardiomyopathy were the strongest predictors of survival., Conclusions: Marathons and half-marathons are associated with a low overall risk of cardiac arrest and sudden death. Cardiac arrest, most commonly attributable to hypertrophic cardiomyopathy or atherosclerotic coronary disease, occurs primarily among male marathon participants; the incidence rate in this group increased during the past decade.

This review describes ultrasound techniques of potential use to high altitude researchers and discusses technical issues related to using ultrasound for high altitude research. Ultrasound allows portable, noninvasive evaluation of many physiologic parameters of interest to high altitude researchers. We discuss techniques that have been extensively used and emerging techniques that can be used to assess parameters of particular interest to high altitude researchers. We do not provide a definitive description of all ultrasound scanning methods but references to instructive sources are included. Potential drawbacks of ultrasound use, such as the need for sometimes extensive training and the potential for interobserver variation, are discussed and strategies for mitigating these are suggested. This review is meant to encourage other high altitude researchers to consider using ultrasound, either as a primary investigative modality or as an adjunct for monitoring parameters of interest in studies of physiology, altitude illness, or therapeutics., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The European Society of Cardiology (ESC) recently published revised criteria for ECG interpretation in the athlete., Objective: To examine the performance of the 2010 ESC ECG criteria in a population of athletes undergoing preparticipation cardiovascular disease screening., Methods: University athletes (n=508) underwent routine medical history/physical examination and ECG before athletic participation. Transthoracic echocardiography (TTE) was also performed on each participant to detect or exclude cardiac findings with relevance to sport participation. Screening test statistics were calculated to determine the performance of the 2010 ESC criteria, and the performance of the 2010 criteria was compared with the 2005 criteria., Results: Application of the 2010 ESC criteria, compared with the 2005 criteria, reduced the number of participants with abnormal ECG findings from 83/508 (16.3%) to 49/508 (9.6%). The reduction in the number of abnormal ECGs was driven by the reclassification of participants with isolated QRS voltage criteria for left ventricular hypertrophy from abnormal to normal. Of the 49 participants with abnormal ECGs, 14/49 (29%) had a single ECG abnormality and 35/49 (71%) had two or more abnormalities. The use of the 2010 criteria was associated with improved specificity (reduction in the false positive rate) and preserved sensitivity when compared with the 2005 criteria., Conclusion: Application of the 2010 ESC criteria for ECG interpretation in the athlete improves the accuracy of an ECG-inclusive preparticipation screening strategy by reducing the rate of false positive ECGs.

Widespread use of anabolic androgenic steroid (AAS) abuse is a rapidly increasing public health concern with an expanding demographic. Previous studies and reports have been exclusive to young individuals at low risk for traditional, non-AAS associated, cardiovascular disease. To date, the impact of AAS use on older patients has not been well characterised. The patient herein presented documents a dramatic case of an older individual who developed decompensated heart failure secondary to illicit use of AAS, highlighting an evolving problem among a rapidly expanding demographic and illustrating that a) AAS, used to alter appearance or augment performance, is no longer an issue confined to young adults; b) older individuals with ageing myocardium may be particularly susceptible to AAS toxicity and may present with fulminate congestive heart failure; and that c) AAS abstinence coupled with traditional heart failure pharmacotherapy may be an effective treatment for this condition.

MicroRNAs (miRNAs) are intracellular mediators of essential biological functions. Recently, plasma-based 'circulating' miRNAs (c-miRNAs) have been shown to control cellular processes, but the c-miRNA response to human exercise remains unknown. We sought to determine whether c-miRNAs are dynamically regulated in response to acute exhaustive cycling exercise and sustained rowing exercise training using a longitudinal, repeated measures study design. Specifically, c-miRNAs involved in angiogenesis (miR-20a, miR-210, miR-221, miR-222, miR-328), inflammation (miR-21, miR-146a), skeletal and cardiac muscle contractility (miR-21, miR-133a), and hypoxia/ischaemia adaptation (miR-21, miR-146a, and miR-210) were measured at rest and immediately following acute exhaustive cycling exercise in competitive male rowers (n = 10, age = 19.1 ± 0.6 years) before and after a 90 day period of rowing training. Distinct patterns of c-miRNA response to exercise were observed and adhered to four major profiles: (1) c-miRNA up-regulated by acute exercise before and after sustained training (miR-146a and miR-222), (2) c-miRNA responsive to acute exercise before but not after sustained training (miR-21 and miR-221), (3) c-miRNA responsive only to sustained training (miR-20a), and (4) non-responsive c-miRNA (miR-133a, miR-210, miR-328). Linear correlations were observed between peak exercise levels of miR-146a and VO2max (r = 0.63, P = 0.003) and between changes in resting miR-20a and changes in VO2max (pre-training vs. post-training, r = 0.73; P = 0.02). Although future work is required, these results suggest the potential value of c-miRNAs as exercise biomarkers and their possible roles as physiological mediators of exercise-induced cardiovascular adaptation.

Background: Transthoracic echocardiographic estimates of peak systolic pulmonary artery pressure are conventionally calculated from the maximal velocity of the tricuspid regurgitation (TR) jet. Unfortunately, there is insufficient TR to determine estimated peak systolic pulmonary artery pressure (EPSPAP) in a significant number of patients. To date, in the absence of TR, no noninvasive method of deriving EPSPAP has been developed., Methods: Five hundred clinically indicated transthoracic echocardiograms were reviewed over a period of 6 months. Patients with pulmonic stenosis were excluded. Pulsed-wave Doppler was used to measure pulmonary artery acceleration time (PAAT) and right ventricular ejection time. Continuous-wave Doppler was used to measure the peak velocity of TR (TR(Vmax)), and EPSPAP was calculated as 4 × TR(Vmax)(2) + 10 mm Hg (to account for right atrial pressure). The relationship between PAAT and EPSPAP was then assessed., Results: Adequate imaging to measure PAAT was available in 99.6% of patients (498 of 500), but 25.3% (126 of 498) had insufficient TR to determine EPSPAP, and 1 patient had significant pulmonic stenosis. Therefore, 371 were included in the final analysis. Interobserver variability for PAAT was 0.97. There were strong inverse correlations between PAAT and TR(Vmax) (r = -0.96), the right atrial/right ventricular pressure gradient (r = -0.95), and EPSPAP (r = -0.95). The regression equation describing the relationship between PAAT and EPSPAP was log(10)(EPSPAP) = -0.004 (PAAT) + 2.1 (P < .001)., Conclusions: PAAT is routinely obtainable and correlates strongly with both TR(Vmax) and EPSPAP in a large population of randomly selected patients undergoing transthoracic echocardiography. Characterization of the relationship between PAAT and EPSPAP permits PAAT to be used to estimate peak systolic pulmonary artery pressure independent of TR, thereby increasing the percentage of patients in whom transthoracic echocardiography can be used to quantify pulmonary artery pressure., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

We sought to determine the clinical and physiologic significance of electrocardiographic complete right bundle branch block (CRBBB) and incomplete right bundle branch block (IRBBB) in trained athletes. The 12-lead electrocardiographic and echocardiographic data from 510 competitive athletes were analyzed. Compared to the 51 age-, sport type-, and gender-matched athletes with normal 12-lead electrocardiographic QRS complex duration, the 44 athletes with IRBBB (9%) and 13 with CRBBB (3%) had larger right ventricular (RV) dimensions, as measured by the basal RV end-diastolic diameter (CRBBB 43 ± 3 mm, IRBBB 38 ± 6 mm, normal QRS complex 35 ± 4 mm, p <0.001) and RV end-diastolic area (CRBBB 33 ± 5, IRBBB 27 ± 7, and normal QRS complex 23 ± 3 cm(2); p <0.001). Athletes with CRBBB also had a relative reduction in the RV systolic function at rest as assessed by the RV fractional area change and peak systolic tissue velocity. Finally, QRS prolongation was associated with parallel increases in interventricular dyssynchrony (basal RV to basal lateral left ventricular peak systolic tissue velocity time difference: CRBBB 112 ± 15, IRBBB 73 ± 33, normal QRS complex 43 ± 39 ms, p <0.001). Despite these findings, no athlete with CRBBB or IRBBB was found to have pathologic structural cardiac disease. In conclusion, among trained athletes, CRBBB and IRBBB appear to be markers of a structural and physiological cardiac remodeling triad characterized by RV dilation, a relative reduction in the RV systolic function at rest, and interventricular dyssynchrony., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Natriuretic peptides have multiple beneficial cardiovascular effects. Previous cross-sectional studies have indicated that obese subjects have lower natriuretic peptide concentrations than those of normal weight. It is not known whether this relative natriuretic peptide deficiency is reversible with weight loss. We studied 132 obese subjects undergoing weight loss surgery with serial measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations at preoperative, early (1 to 2 months), and late postoperative (6 months) points. In addition, 20 subjects also underwent echocardiography at baseline and 6 months after surgery. Significant weight loss was observed after surgery (median body mass index 45.1, 41.0, and 32.9 kg/m(2) for the 3 corresponding points, analysis of variance p <0.001). The median NT-proBNP levels increased substantially (31.6, 66.9, and 84.9 pg/ml; p <0.001). The average intrasubject increase in NT-proBNP at the 2 postoperative points was 3.4 and 5.0 times the preoperative level (p <0.001 for both points vs preoperatively). In the multivariate regression models adjusted for clinical characteristics and insulin resistance, the strongest predictor of the change in NT-proBNP level 6 months after weight loss surgery was the change in weight (p = 0.03). Echocardiography showed a mean intrasubject reduction in left ventricular mass index of 18% (p <0.001) and mild improvements in diastolic function, with no change in ejection fraction. In conclusion, we have demonstrated that weight loss is associated with early and sustained increases in NT-proBNP concentrations, despite evidence of preserved systolic and improved diastolic function. These findings suggest a direct, reversible relation between obesity and reduced natriuretic peptide levels., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: left ventricular (LV) rotation results from contraction of obliquely oriented myocardial fibers. The net difference between systolic apical counterclockwise rotation and basal clockwise rotation is left ventricular torsion (LVT). Although LVT is altered in various cardiac diseases, determinants of LVT are incompletely understood., Methods and Results: LV end-diastolic volume, LV apical and basal rotation, peak systolic LVT, and peak early diastolic untwisting rate were measured by speckle-tracking echocardiography in healthy subjects (n=8) before and after infusion of a weight-based normal saline bolus (2.1±0.3 L). Saline infusion led to a significant increase in end-diastolic LV internal diameter (45.9±3.7 versus 47.6±4.2 mm; P=0.002) and LV end-diastolic volume (90.0±21.6 versus 98.3±19.6 mL; P=0.01). Stroke volume (51.3±10.9 versus 63.0±15.5 mL; P=0.003) and cardiac output (3.4±0.8 versus 4.4±1.5 L/min; P=0.007) increased, whereas there was no change in heart rate and blood pressure. There was a significant increase in the magnitude of peak systolic apical rotation (7.5±2.4° versus 10.5±2.8°; P<0.001) but no change in basal rotation (-4.1±2.3° versus -4.8±3.1°; P=0.44). Accordingly, peak systolic LVT increased by 33% after saline infusion (11.2±1.3° versus 14.9±1.7°; P<0.001). This saline-induced increase in LVT was associated with a marked increase in peak early diastolic untwisting rate (72.3±21.4 versus 136.8±30.0 degrees/s; P<0.001)., Conclusions: peak systolic LVT and peak early diastolic untwisting rate are preload-dependent. Changes in LV preload should be considered when interpreting results of future LVT studies.

Objectives: We sought to examine the effect of endurance exercise training (EET) on peak systolic left ventricular torsion (LVT) and peak early diastolic untwisting rate (UTR)., Background: Left 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., Methods: A 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., Results: Participants experienced LV eccentric hypertrophy, characterized by increased LV end-diastolic volume (80.8 ± 8.7 ml/m(2) vs. 91.3 ± 8.0 ml/m(2), p < 0.001) and LV mass (101.3 ± 11.4 g/m(2) vs. 115.7 ± 12.6 g/m(2), 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., Conclusions: Participation 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., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 (>or=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.

Background: The prognostic value of the New York Heart Association classification (NYHAC) in acutely decompensated heart failure (ADHF) is unknown., Objectives: We sought to determine the relative value of NYHAC among patients with concomitantly measured amino-terminal pro-B type natriuretic peptide (NT-proBNP) at presentation with ADHF., Materials and Methods: NYHAC was determined for 720 patients with ADHF and 1-year mortality status was examined. Cox-proportional hazards analysis compared the prognostic accuracy of NYHAC with other ADHF risk measures., Results: NYHAC had a significant univariate association with 1-year mortality status (HR 1.41, 95% confidence interval (CI) 1.03-1.94; p = 0.03) but was not a significant predictor of death in a multivariable model that included NT-proBNP (HR 2.14; 95% CI 1.65-2.81, p < 0.001)., Conclusions: In contrast to objective measures such as NT-proBNP, the NYHAC appears to provide limited prognostic information among individuals with ADHF.

Pericardial disease is an important cause of morbidity and mortality in patients with cardiovascular disease. Inflammatory diseases of the pericardium constitute a spectrum ranging from acute pericarditis to chronic constrictive pericarditis. Other important entities that involve the pericardium include benign and malignant pericardial masses, pericardial cysts, and diverticula, as well as congenital absence of the pericardium. Recent advances in multimodality noninvasive cardiac imaging have solidified its role in the management of patients with suspected pericardial disease. The physiologic and structural information obtained from transthoracic echocardiography and the anatomic detail provided by cardiac computed tomography and magnetic resonance have led to growing interest in the complementary use of these techniques. Optimal management of the patient with suspected pericardial disease requires familiarity with the key imaging modalities and the ability to choose the appropriate imaging tests for each patient. This report reviews the imaging modalities most useful in the assessment of patients with pericardial disease, with an emphasis on the complementary value of multimodality cardiac imaging., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Staged ascent (SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure (PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent (DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximately 760 torr), after DA to simulated high altitude (hypobaric chamber, P(B) approximately 460 torr), and at 2 times points (90 min and 4 days) during exposure to terrestrial high altitude (P(B) approximately 460 torr) after SA (7 days, moderate altitude, P(B) approximately 548 torr). Alveolar oxygen pressure (Pao(2)) and arterial oxygenation saturation (Sao(2)) were measured at each time point. Compared to mean PAP at SL (mean +/- SD, 14 +/- 3 mmHg), mean PAP increased after DA to 37 +/- 8 mmHg (Delta = 24 +/- 10 mmHg, p < 0.001) and was negatively correlated with both Pao(2) (r(2) = 0.57, p = 0.011) and Sao(2) (r(2) = 0.64, p = 0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4 mmHg (Delta = 11 +/- 6 mmHg, p < 0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5 mmHg, p = not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia.

Unlabelled: There is significant individual variability in the cardiac adaptation that occurs in response to exercise training. Factors associated with this variability remain incompletely understood. To date, the relationship between the competition level at which athletes participate and their underlying cardiac parameters has not been explored., Purpose: The purpose of this study was to determine whether parameters of cardiac structure and function differ significantly among elite competitive rowers (ER), subelite competitive rowers (SR), and sedentary controls (C)., Methods: Cardiac parameters were assessed in ER (n = 20), SR (n = 20), and C (n = 20) using two-dimensional, tissue Doppler, and speckled-tracking echocardiography., Results: Physiologic cardiac remodeling was present in both ER and SR as evidenced by the significant differences in the majority of structural and functional parameters in both rower groups when compared with C. When compared with SR, ER were found to have greater left ventricular (LV) end-diastolic volume (76 +/- 6 vs 71 +/- 8 mL x m(-2), P = 0.02), LV mass (150 +/- 11 vs 134 +/- 16 g x m(-2), P = 0.002), and right ventricular (RV) end-diastolic chamber dimensions (15.6 +/- 0.9 vs 13.9 +/- 1.5 cm(2) x m(-2), P < 0.001). Further, ER demonstrated significantly more enhancement of RV systolic function (peak strain = 36% +/- 7% vs 31% +/- 6%, P = 0.008) and late diastolic relaxation in both the LV (A' = 4.2 +/- 1.3 vs 3.2 +/- 0.9 cm x s(-1), P = 0.01) and the RV (A' = 6.6 +/- 1.4 vs 4.3 +/- 1.3 cm x s(-1), P < 0.001)., Conclusions: Although cardiac remodeling occurs in both ER and SR, specific aspects of cardiac structure and function differ between rowers who compete at the elite and the subelite levels of sport.

Background: Serial measurements of N-terminal pro-B type natriuretic peptide (NT-proBNP) provide prognostic information in patients with chronic heart failure (HF). Changes in NT-proBNP concentrations parallel prognosis; however, it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT-proBNP concentrations is superior to standard HF care alone., Aims: The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to standard of care HF management., Methods: In a prospective randomized single-center trial, subjects with New York Heart Association class II to IV systolic HF (left ventricular ejection fraction < or =40%) will be enrolled. Both groups will receive standard HF management (with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF), whereas one group ("NT-proBNP") will also have treatment adjustments to reduce NT-proBNP concentrations < or =1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period; secondary end points will include effects of NT-proBNP-guided care on cardiac structure and function, quality of life, and total costs of care., Results: Enrollment began in 2006; of the original 300 planned, thus far, 151 subjects have been randomized. Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm. Full results are expected in 2010., Conclusions: The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to standard of care HF management (www.clinicaltrials.gov identifier NCT00351390)., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Although cardiovascular screening is recommended for athletes before participating in sports, the role of 12-lead electrocardiography (ECG) remains uncertain. To date, no prospective data that compare screening with and without ECG have been available., Objective: To compare the performance of preparticipation screening limited to medical history and physical examination with a strategy that integrates these with ECG., Design: Cross-sectional comparison of screening strategies., Setting: University Health Services, Harvard University, Cambridge, Massachusetts., Participants: 510 collegiate athletes who received cardiovascular screening before athletic participation., Measurements: Each participant had routine history and examination-limited screening and ECG. They received transthoracic echocardiography (TTE) to detect or exclude cardiac findings with relevance to sports participation. The performance of screening with history and examination only was compared with that of screening that integrated history, examination, and ECG., Results: Cardiac abnormalities with relevance to sports participation risk were observed on TTE in 11 of 510 participants (prevalence, 2.2%). Screening with history and examination alone detected abnormalities in 5 of these 11 athletes (sensitivity, 45.5% [95% CI, 16.8% to 76.2%]; specificity, 94.4% [CI, 92.0% to 96.2%]). Electrocardiography detected 5 additional participants with cardiac abnormalities (for a total of 10 of 11 participants), thereby improving the overall sensitivity of screening to 90.9% (CI, 58.7% to 99.8%). However, including ECG reduced the specificity of screening to 82.7% (CI, 79.1% to 86.0%) and was associated with a false-positive rate of 16.9% (vs. 5.5% for screening with history and examination only)., Limitation: Definitive conclusions regarding the effect of ECG inclusion on sudden death rates cannot be made., Conclusion: Adding ECG to medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However, this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are used., Primary Funding Source: None.

Left ventricular (LV) hypertrophy is a well-established, but highly variable, finding among exercise-trained persons. The causes for the variability in LV remodeling in response to exercise training remain incompletely understood. The present study sought to determine whether a family history of hypertension is a determinant of the cardiac response to exercise training. The cardiac parameters in 60 collegiate rowers (30 men/30 women; age 19.8 +/- 1.1 years) with (family history positive [FH+], n = 22) and without (family history negative [FH-], n = 38) a FH of hypertension were studied with echocardiography before and after 90 days of rowing training. The LV mass increased significantly in both groups. However, the LV mass increased significantly more in FH- persons (Delta 17 +/- 5 g/m(2)) than in FH+ persons (Delta 9 +/- 6 g/m(2), p <0.001) with distinctly differently patterns of LV hypertrophy between the 2 groups. FH- athletes experienced eccentric LV hypertrophy (relative wall thickness index 0.39 +/- 0.4) characterized by LV dilation. In contrast, FH+ athletes developed concentric LV hypertrophy (relative wall thickness index 0.44 +/- 0.3; p <0.001) characterized by LV wall thickening. Furthermore, the eccentric LV remodeling in FH- athletes was associated with a more robust enhancement of LV diastolic function than the concentric LV remodeling that occurred in FH+ athletes. In conclusion, these findings suggest that patterns of exercise-induced LV remodeling are strongly associated with FH history status.