Malissa J. Wood

Myocardial Injury and Ventricular Dysfunction Related to Training Levels Among Nonelite Participants in the Boston Marathon

Background— Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results— We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler–derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, >60% of participants had increased cTnT >99th percentile of normal (>0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (≥0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=−0.70, P<0.001) and inversely with training mileage (r=−0.71, P<0.001). Compared with athletes training >45 miles/wk, athletes who trained ≤35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16±5% versus 25±4%, P<0.001), myocyte injury (cTnT 0.09 versus <0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). Conclusions— Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Cardiovascular screening in college athletes with and without electrocardiography: a cross-sectional study.

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.

Exercise-Induced Cardiac Troponin Elevation Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

Metabolic Signatures of Exercise in Human Plasma

Measurement by mass spectrometry of 200 blood metabolites reveals that individuals who are more fit respond more effectively to exercise, as shown by larger exercise-induced increase in glycerol. What Happens When You Run the Boston Marathon? We used to call it toil; now, we call it exercise. The human body has evolved to perform physical labor, and modern sedentary lifestyles are at odds with this evolutionary mandate. This disconnect makes it all the more imperative that we understand the physiology of how the body converts fuel to work. Lewis and colleagues have moved us toward that goal by comprehensively surveying blood metabolites in people of varying fitness levels before and during exercise. Through the use of a high-sensitivity mass spectrometry method, they have characterized these exercise-induced metabolic changes in unprecedented detail. The authors measured 200 blood metabolites in groups of people before, during, and after exercise on a treadmill. They found that the elevated glycolysis, lipolysis, and amino acid catabolism that occur in skeletal muscle cells during use are reflected in a rise in marker metabolites of these processes in blood. Also appearing in the blood after exercise were niacinamide, which enhances insulin release and improves glycemic control, and allantoin, an indicator of oxidative stress. Even when other variables were controlled for, the people who were more fit—as measured by their maximum oxygen use—exhibited more lipolysis during exercise (98% increase) than did the less fit (48% increase) participants or those who developed heart ischemia upon exertion (18% increase). Even more striking was the increase in lipolysis (1128%) in runners after they finished the Boston Marathon, a 26.2-mile run through the winding roads of Boston and its environs. From these data, the authors could not tell whether the more well-conditioned individuals were fitter because their metabolism used fat more effectively or whether, once attaining fitness, these able-bodied metabolic systems were better at burning fat. A mechanistic clue is provided by a final experiment in which the authors show that a combination of six of the metabolites elevated by exercise reflects an increase in glucose utilization and lipid metabolism in skeletal muscle cells, whereas none of the individual elevated molecules signal this effect. Thus, a cost of our sedentary lives may be to deoptimize the operation of the complicated system that is human metabolism. Sorting out how this backsliding occurs and how to restore the vigor of our metabolism will be facilitated by the findings and tools reported here. Exercise provides numerous salutary effects, but our understanding of how these occur is limited. To gain a clearer picture of exercise-induced metabolic responses, we have developed comprehensive plasma metabolite signatures by using mass spectrometry to measure >200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid cycle span 2 expansion (succinate, malate, and fumarate), and lipolysis (glycerol), as well as modulators of insulin sensitivity (niacinamide) and fatty acid oxidation (pantothenic acid). Metabolites that were highly correlated with fitness parameters were found in subjects undergoing acute exercise testing and marathon running and in 302 subjects from a longitudinal cohort study. Exercise-induced increases in glycerol were strongly related to fitness levels in normal individuals and were attenuated in subjects with myocardial ischemia. A combination of metabolites that increased in plasma in response to exercise (glycerol, niacinamide, glucose-6-phosphate, pantothenate, and succinate) up-regulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeletal muscle in vitro. Plasma metabolic profiles obtained during exercise provide signatures of exercise performance and cardiovascular disease susceptibility, in addition to highlighting molecular pathways that may modulate the salutary effects of exercise.

State-of-the-Art PaperExercise-Induced Cardiac Troponin Elevation: Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

Athlete's Heart and Cardiovascular Care of the Athlete: Scientific and Clinical Update

“The physiologic capabilities of the heart are enormous, and in judging the effect of any undue exertion on it, we must not regard the murmurs of the irregularity alone, but must also consider carefully, the way in which the heart is doing its work, its strength, as shown by its ability to maintain proper arterial tension, and its recuperative power. As with other muscles, not size but quality tells in the long run.”1 Eugene Darling The heart of the athlete has intrigued clinicians and scientists for more than a century. Early investigations in the late 1800s and early 1900s documented cardiac enlargement and bradyarrhythmias in individuals with above-normal exercise capacity and no attendant signs of cardiovascular disease. Since that time, scientific understanding of the association between sport participation and specific cardiac abnormalities has paralleled advances in cardiovascular diagnostic techniques. It is now well established that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. Recent increases in the popularity of recreational exercise and competitive athletics have led to a growing number of individuals exhibiting this phenomenon. This review provides an up-to-date summary of the science of cardiac remodeling in athletes and an overview of common clinical issues that are encountered in the cardiovascular care of the athlete. Initial reports describing cardiac enlargement in athletes date back to the late 1890s. In Europe, the Swedish clinician Henschen2 used the rudimentary yet elegant physical examination skills of auscultation and percussion to demonstrate increased cardiac dimensions in elite Nordic skiers. Similar observations were made during the same year by Eugene Darling1 of Harvard University in university rowers. In the early 1900s, Paul Dudley White3 studied radial pulse rate and pattern among Boston Marathon competitors, and was the first to report marked resting sinus …

Tai Chi Exercise in Patients With Chronic Heart Failure: A Randomized Clinical Trial

BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure (HF); this has not been rigorously tested in a large clinical sample. We sought to investigate whether tai chi, as an adjunct to standard care, improves functional capacity and quality of life in patients with HF. METHODS A single-blind, multisite, parallel-group, randomized controlled trial evaluated 100 outpatients with systolic HF (New York Heart Association class I-III, left ventricular ejection fraction ≤40%) who were recruited between May 1, 2005, and September 30, 2008. A group-based 12-week tai chi exercise program (n = 50) or time-matched education (n = 50, control group) was conducted. Outcome measures included exercise capacity (6- minute walk test and peak oxygen uptake) and disease-specific quality of life (Minnesota Living With Heart Failure Questionnaire). RESULTS Mean (SD) age of patients was 67 (11) years; baseline values were left ventricular ejection fraction, 29% (8%) and peak oxygen uptake, 13.5 mL/kg/min; the median New York Heart Association class of HF was class II. At completion of the study, there were no significant differences in change in 6-minute walk distance and peak oxygen uptake (median change [first quartile, third quartile], 35 [-2, 51] vs 2 [-7, 54] meters, P = .95; and 1.1 [-1.1, 1.5] vs -0.5 [-1.2, 1.8] mL/kg/min, P = .81) when comparing tai chi and control groups; however, patients in the tai chi group had greater improvements in quality of life (Minnesota Living With Heart Failure Questionnaire, -19 [-23, -3] vs 1 [-16, 3], P = .02). Improvements with tai chi were also seen in exercise self-efficacy (Cardiac Exercise Self-efficacy Instrument, 0.1 [0.1, 0.6] vs -0.3 [-0.5, 0.2], P < .001) and mood (Profile of Mood States total mood disturbance, -6 [-17, 1] vs -1 [-13, 10], P = .01). CONCLUSION Tai chi exercise may improve quality of life, mood, and exercise self-efficacy in patients with HF. Trial Registration clinicaltrials.gov Identifier: NCT00110227.

Perioperative Echocardiographic Examination for Ventricular Assist Device Implantation

Ventricular assist devices (VADs) are systems for mechanical circulatory support of the patient with severe heart failure. Perioperative transesophageal echocardiography is a major component of patient management, and important for surgical and anesthetic decision making. In this review we present the rationale and available data for a comprehensive echocardiographic assessment of patients receiving a VAD. In addition to the standard examination, device-specific pre-, intra-, and postoperative considerations are essential to the echocardiographic evaluation. These include: (a) the pre-VAD insertion examination of the heart and large vessels to exclude significant aortic regurgitation, tricuspid regurgitation, mitral stenosis, patent foramen ovale, or other cardiac abnormality that could lead to right-to-left shunt after left VAD placement, intracardiac thrombi, ventricular scars, pulmonic regurgitation, pulmonary hypertension, pulmonary embolism, and atherosclerotic disease in the ascending aorta; and to assess right ventricular function; and (b) the post-VAD insertion examination of the device and reassessment of the heart and large vessels. The examination of the device aims to confirm completeness of device and heart deairing, cannulas alignment and patency, and competency of device valves using two-dimensional, and color, continuous and pulsed wave Doppler modalities. The goal for the heart examination after implantation should be to exclude aortic regurgitation, or an uncovered right-to-left shunt; and to assess right ventricular function, left ventricular unloading, and the effect of device settings on global heart function. The variety of VAD models with different basic and operation principles requires specific echocardiographic assessment targeted to the characteristics of the implanted device.

Performance of the 2010 European Society of Cardiology criteria for ECG interpretation in athletes

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.

Early Repolarization Pattern in Competitive Athletes Clinical Correlates and the Effects of Exercise Training

Background— Inferior lead early repolarization pattern (ERP) recently has been associated with sudden cardiac death. Although ERP is common among athletes, prevalence, ECG lead distribution, clinical characteristics, and effects of physical training remain uncertain. We sought to examine the nonanterior ERP in competitive athletes. Methods and Results— ERP was assessed in a cross-sectional cohort of collegiate athletes (n=879). The relationship between ERP and cardiac structure were then examined in a longitudinal subgroup (n=146) before and after a 90-day period of exercise training. ERP was defined as J-point elevation ≥0.1 mV in at least 2 leads within a nonanterior territory (inferior [II, III, aVF] or lateral territory [I, aVL, V4-V6]). Nonanterior ERP was present in 25.1% (221/879) of athletes, including the inferior subtype in 3.8% (33/879). Exercise training led to significant increases in the prevalence of ERP and the inferior subtype, but there were no associations between ERP and echocardiographic measures of left ventricular remodeling. In a multivariable model, ERP was associated with black race (odds ratio [OR], 5.84; 95% CI, 3.54 to 9.61; P <0.001), increased QRS voltage (OR, 2.08; 95% CI, 1.71 to 2.52; P <0.001), and slower heart rate (OR, 1.54; 95% CI, 1.26 to 1.87; P <0.001). Conclusions— Nonanterior ERP, including the inferior subtype, is common and has strong clinical associations among competitive athletes. The finding of increased ERP prevalence after intense physical training establishes a strong association between exercise and ERP.Background— Inferior lead early repolarization pattern (ERP) recently has been associated with sudden cardiac death. Although ERP is common among athletes, prevalence, ECG lead distribution, clinical characteristics, and effects of physical training remain uncertain. We sought to examine the nonanterior ERP in competitive athletes. Methods and Results— ERP was assessed in a cross-sectional cohort of collegiate athletes (n=879). The relationship between ERP and cardiac structure were then examined in a longitudinal subgroup (n=146) before and after a 90-day period of exercise training. ERP was defined as J-point elevation ≥0.1 mV in at least 2 leads within a nonanterior territory (inferior [II, III, aVF] or lateral territory [I, aVL, V4-V6]). Nonanterior ERP was present in 25.1% (221/879) of athletes, including the inferior subtype in 3.8% (33/879). Exercise training led to significant increases in the prevalence of ERP and the inferior subtype, but there were no associations between ERP and echocardiographic measures of left ventricular remodeling. In a multivariable model, ERP was associated with black race (odds ratio [OR], 5.84; 95% CI, 3.54 to 9.61; P<0.001), increased QRS voltage (OR, 2.08; 95% CI, 1.71 to 2.52; P<0.001), and slower heart rate (OR, 1.54; 95% CI, 1.26 to 1.87; P<0.001). Conclusions— Nonanterior ERP, including the inferior subtype, is common and has strong clinical associations among competitive athletes. The finding of increased ERP prevalence after intense physical training establishes a strong association between exercise and ERP.