Aaron L. Baggish

Cardiac arrest during long-distance running races

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.

Electrocardiographic interpretation in athletes: the ‘Seattle Criteria’

Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athletes ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13–14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD.

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

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).

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.

Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training

Non‐technical summary  MicroRNA (miRNA) molecules are essential intracellular mediators of numerous biological processes including angiogenesis, inflammation, and mitochondrial metabolism. Recently, it has been shown that miRNAs are secreted into the bloodstream and that circulating miRNAs (c‐miRNAs) may serve important endocrine functions. This study examined plasma profiles of specific c‐miRNAs in healthy competitive athletes at rest and during exhaustive exercise testing, before and after a 90 day period of exercise training. In this setting, we observed four distinct patterns of c‐miRNA response to exercise: (1) c‐miRNAs up‐regulated by acute exhaustive exercise before and after sustained exercise training, (2) c‐miRNAs responsive to acute exhaustive exercise before but not after sustained exercise training, (3) c‐miRNAs responsive only to sustained exercise training, and (4) non‐responsive c‐miRNAs. These findings set the stage for further work aimed at defining the role of c‐miRNAs as fitness biomarkers and physiological mediators of exercise‐induced cardiovascular adaptation.

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 …

Antiparasitic Agent Atovaquone

Atovaquone is a unique naphthoquinone with broad-spectrum antiprotozoal activity. It is effective for the treatment and prevention of Pneumocystis carinii pneumonia (PCP), it is effective in combination with proguanil for the treatment and prevention of malaria, and it is effective in combination with azithromycin for the treatment of babesiosis. There is also limited experience with other protozoans. It has found a role in the management of diseases such as malaria and PCP because drug resistance, intolerable side effects of medications, and variable efficacies have occurred with existing treatments. Although the antimicrobial actions of the naphthoquinones were demonstrated more than 50 years ago, clinical trials leading to Food and Drug Administration (FDA) approval of atovaquone have occurred largely over the last decade. This paper reviews the pharmacology and mechanism of action, clinical trials, and current uses of atovaquone.

Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction The Role of Abnormal Peripheral Oxygen Extraction

Background—Exercise capacity as measured by peak oxygen uptake (VO2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of VO2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF. Methods and Results—We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak VO2=13.9±0.5 mL kg−1 min−1, mean±SEM, and HFrEF, n=56, peak VO2=12.1±0.5 mL kg−1 min−1) and 24 control subjects (peak VO2 27.0±1.7 mL kg−1 min−1). Peak exercise C(a-v)o2 was lower in HFpEF compared with HFrEF (11.5±0.27 versus 13.5±0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, CaO2, or cardiac filling pressures. Peak C(a-v)o2 and peak heart rate emerged as the leading predictors of peak VO2 in HFpEF. Impaired peripheral o2 extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). Conclusions—In the first study to directly measure C(a-v)o2 throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o2 was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o2 extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention.