Benjamin D Levine

University of Texas Southwestern Medical Center, Dallas, Texas, United States

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Publications (415)2165.2 Total impact

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    ABSTRACT: To assess the hemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRV). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. 14 asymptomatic patients (34 ± 10y) with TGA and SRV were enrolled in a 12 week exercise training program (moderate and high intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: a) submaximal and peak; b) prolonged (60 min) submaximal endurance and c) high intensity intervals. Oxygen uptake (VO2; Douglas bag technique), cardiac output (Qc, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak VO2 , Qc, and stroke volume (SV), a blunted Qc/VO2 slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, p<0.001) compared with controls. After training, TGA patients increased peak VO2 by 6%±8.5%, similar to controls (interaction p = 0.24). The magnitude of SV reserve on initial testing correlated with Qc training response (r = 0.58, p = 0.047), though overall, no change in peak Qc was observed. Hs-troponin-T and NT pro-BNP were low and did not change with acute exercise or after training. TGA patients with SRVs in this study safely participated in exercise training and improved peak VO2 . Neither prolonged submaximal exercise, high intensity intervals, or short-term exercise training seem to injure the systemic right ventricle. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 03/2015; DOI:10.1113/JP270280 · 4.38 Impact Factor
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    ABSTRACT: Patients with the postural orthostatic tachycardia syndrome (POTS) are primarily premenopausal women, which may be attributed to female sex hormones. We tested the hypothesis that hormonal fluctuations of the menstrual cycle alter sympathetic neural activity and orthostatic tolerance in POTS women. Ten POTS women were studied during the early follicular (EF) and mid-luteal (ML) phases of the menstrual cycle. Haemodynamics and muscle sympathetic nerve activity (MSNA) were measured while supine, and during 60° upright tilt for 45 min or until presyncope, cold pressor test (CPT), and Valsalva manoeuvres. Blood pressure and total peripheral resistance were higher during rest and tilting in the ML than EF phase; however heart rate, stroke volume, and cardiac output were similar between phases. There were no differences in MSNA burst frequency (8 ± 8 [SD] EF phase vs. 10 ± 10 bursts/min ML phase at rest; 34 ± 15 EF phase vs. 36 ± 16 bursts/min ML phase at 5 min tilt), burst incidence, or total activity, or in the cardiovagal and sympathetic baroreflex sensitivities between phases in any condition. The incidence of presyncope was also the same between phases. There were no differences in haemodynamic or sympathetic responses to CPT or Valsalva. These results suggest that the menstrual cycle does not affect sympathetic neural activity, but modulates blood pressure and vasoconstriction in POTS women during tilting. Thus, factors other than sympathetic neural activity are likely responsible for symptoms of orthostatic intolerance across the menstrual cycle in women with POTS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Journal of Physiology 02/2015; DOI:10.1113/JP270088 · 4.54 Impact Factor
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    ABSTRACT: Introduction. This controlled nonrandomized parallel groups trial investigated the effects on performance, VO2 and hemoglobin mass (tHbmass) of 4 preparatory in-season training interventions: living and training at moderate altitude for 3 and 4 weeks (Hi-Hi3, Hi-Hi), living high and training high and low (Hi-HiLo, 4 weeks), and living and training at sea level (SL) (Lo-Lo, 4 weeks). Methods. From 61 elite swimmers, 54 met all inclusion criteria and completed time trials over 50 and 400 m crawl (TT50, TT400), and 100 (sprinters) or 200 m (non-sprinters) at best stroke (TT100/TT200). and heart rate were measured with an incremental 4x200-m test. Training load was estimated using TRIMPc and session RPE. Initial measures (PRE) were repeated immediately (POST) and once weekly on return to SL (PostW1 to PostW4). tHbmass was measured in duplicate at PRE and once weekly during the camp with CO rebreathing. Effects were analyzed using mixed linear modeling. Results. TT100 or TT200 was worse or unchanged immediately POST, but improved by ~3.5% regardless of living or training at SL or altitude following at least 1 week of sea level recovery. Hi-HiLo achieved a greater improvement two (5.3%) and four weeks (6.3%) after the camp. Hi-HiLo also improved more in TT400 and TT50 two (4.2% and 5.2%, respectively) and four weeks (4.7% and 5.5%) from return. This performance improvement was not linked linearly to changes in or tHbmass. Conclusion. A well- implemented 3- or 4-week training camp may impair performance immediately, but clearly improves performance even in elite swimmers after a period of SL recovery. Hi-HiLo for 4 weeks improves performance in swimming above and beyond altitude and SL controls, through complex mechanisms involving altitude living and SL training effects.
    Medicine and science in sports and exercise 01/2015; DOI:10.1249/MSS.0000000000000626 · 4.48 Impact Factor
  • Rong Zhang, Wanpen Vongpatanasin, Benjamin D Levine
    JAMA Internal Medicine 01/2015; 175(1):144. DOI:10.1001/jamainternmed.2014.6971 · 13.25 Impact Factor
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    Circulation Heart Failure 01/2015; 8(1):209-20. DOI:10.1161/CIRCHEARTFAILURE.113.001420 · 6.68 Impact Factor
  • Satyam Sarma, Benjamin D Levine
    Circulation Cardiovascular Imaging 12/2014; 8(1). DOI:10.1161/CIRCIMAGING.114.002836 · 5.80 Impact Factor
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    ABSTRACT: To assess the effect of cardiorespiratory fitness on the association between the initiation of statin therapy and incident diabetes. In a prospective observational study, we studied 6519 generally healthy men and 2334 women with two preventive health examinations from December 15, 1998 through December 18, 2013 which included measurement of fitness levels, statin therapy, risk factors for diabetes, and incident diabetes. 93 cases of incident diabetes occurred during an average follow-up of 3.0 years. After multivariable adjustment, an increased odds of incident diabetes with statin use was observed in those patients with impaired fasting glucose at baseline (odds ratio [OR]: 2.15, [95% CI:1.26 to 3.67]), but not among individuals with normal glucose levels (OR:1.85, [95% CI: 0.76 to 4.52]). Cardiorespiratory fitness attenuated but did not eliminate the increased risk of incident diabetes with statin use. In a population of relatively healthy patients, statin use was not associated with incident diabetes in patients with normal fasting glucose at baseline. However, it was associated with incident diabetes in those patients with impaired fasting glucose at baseline, though this risk was substantially reduced by increasing fitness. In addition, increasing cardiorespiratory fitness was inversely associated with incident diabetes whether or not a patient was treated with a statin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 239(1):43-49. DOI:10.1016/j.atherosclerosis.2014.12.051 · 3.71 Impact Factor
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    ABSTRACT: We thank Lipman [1] for his attention to detail and swift response to our recent publication [2], and believe his letter provides an educational opportunity regarding the management of exertional heat stroke (EHS) and thermal emergencies in general.Although the controversial [3, 4] Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Heat-Related Illness [5] cites a review article [6] which references a book chapter [7] suggesting a strict definition of heat stroke as “…greater than 40 Celsius”, recent literature suggests that use of an absolute temperature threshold for the treatment of EHS is not supported by current knowledge. Lipman’s contention that it is at this exact temperature where cell injury, apoptosis, and systemic symptoms occur is not accurate. There is simply no evidence of a binary threshold of temperature at which the EHS pathways mentioned are initiated. In the spirit of education, we wish to point the reader to the three following princ ...
    Sports Medicine 12/2014; DOI:10.1007/s40279-014-0295-2 · 5.32 Impact Factor
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    ABSTRACT: Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal-adrenal system (e.g., low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. Blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30° and 60° for 5 min each) in 9 Asians [32±1 (SE) yrs] and 12 Caucasians (29±1 yrs) prospectively during pre, early (≤8 wks of gestation) and late (32–36 wks) pregnancy, and post-partum (6–10 wks after delivery). Supine MSNA increased with pregnancy in both groups (P<0.001); it was significantly lower in Asians than Caucasians (14±3 vs. 23±3 bursts/min and 16±5 vs. 30±3 bursts/min in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P<0.001), but was restored during late pregnancy. HR increased during pregnancy (P<0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31±6 vs. 49±3 bursts/min at 60° tilt; P = 0.003). Upright BP was lower in Asians even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P<0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal-adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy.This article is protected by copyright. All rights reserved
    The Journal of Physiology 12/2014; DOI:10.1113/jphysiol.2014.282277 · 4.38 Impact Factor
  • Qi Fu, Benjamin D Levine
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    ABSTRACT: Patients with the Postural Orthostatic Tachycardia Syndrome (POTS) have orthostatic intolerance, as well as exercise intolerance. Peak oxygen uptake (VO2peak) is generally lower in these patients compared with healthy sedentary individuals, suggesting a lower physical fitness level. During acute exercise, POTS patients have an excessive increase in heart rate and reduced stroke volume for each level of absolute workload; however, when expressed at relative workload (%VO2peak), there is no difference in the heart rate response between patients and healthy individuals. The relationship between cardiac output and VO2 is similar between POTS patients and healthy individuals. Short-term (i.e., 3months) exercise training increases cardiac size and mass, blood volume, and VO2peak in POTS patients. Exercise performance is improved after training. Specifically, stroke volume is greater and heart rate is lower at any given VO2 during exercise after training versus before training. Peak heart rate is the same but peak stroke volume and cardiac output are greater after training. Heart rate recovery from peak exercise is significantly faster after training, indicating an improvement in autonomic circulatory control. These results suggest that patients with POTS have no intrinsic abnormality of heart rate regulation during exercise. The tachycardia in POTS is due to a reduced stroke volume. Cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve exercise performance in these patients. Copyright © 2014 Elsevier B.V. All rights reserved.
    Autonomic neuroscience: basic & clinical 11/2014; 188. DOI:10.1016/j.autneu.2014.11.008 · 1.82 Impact Factor
  • Qi Fu, Benjamin D. Levine
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    ABSTRACT: Patients with the Postural Orthostatic Tachycardia Syndrome (POTS) have orthostatic intolerance, as well as exercise intolerance. Peak oxygen uptake (VO2peak) is generally lower in these patients compared with healthy sedentary individuals, suggesting a lower physical fitness level. During acute exercise, POTS patients have an excessive increase in heart rate and reduced stroke volume for each level of absolute workload; however, when expressed at relative workload (%VO2peak), there is no difference in the heart rate response between patients and healthy individuals. The relationship between cardiac output and VO2 is similar between POTS patients and healthy individuals. Short-term (i.e., 3 months) exercise training increases cardiac size and mass, blood volume, and VO2peak in POTS patients. Exercise performance is improved after training. Specifically, stroke volume is greater and heart rate is lower at any given VO2 during exercise after training versus before training. Peak heart rate is the same but peak stroke volume and cardiac output are greater after training. Heart rate recovery from peak exercise is significantly faster after training, indicating an improvement in autonomic circulatory control. These results suggest that patients with POTS have no intrinsic abnormality of heart rate regulation during exercise. The tachycardia in POTS is due to a reduced stroke volume. Cardiac remodeling and blood volume expansion associated with exercise training increase physical fitness and improve exercise performance in these patients.
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    ABSTRACT: 10.1161/CIRCHEARTFAILURE.114.001615
    Circulation Heart Failure 11/2014; DOI:10.1161/CIRCHEARTFAILURE.114.001615 · 5.95 Impact Factor
  • JACC Cardiovascular Imaging 11/2014; DOI:10.1016/j.jcmg.2014.07.019 · 6.99 Impact Factor
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    ABSTRACT: : While the preparticipation physical evaluation (PPE) is widely accepted, its usage and content are not standardized. Implementation is affected by cost, access, level of participation, participant age/sex, and local/regional/national mandate. Preparticipation physical evaluation screening costs are generally borne by the athlete, family, or club. Screening involves generally agreed-upon questions based on expert opinion and tested over decades of use. No large-scale prospective controlled tracking programs have examined PPE outcomes. While the panel did not reach consensus on electrocardiogram (ECG) screening as a routine part of PPE, all agreed that a history and physical exam focusing on cardiac risk is essential, and an ECG should be used where risk is increased. The many areas of consensus should help the American College of Sports Medicine and Fédération Internationale du Médicine du Sport in developing a universally accepted PPE. An electronic PPE, using human-centered design, would be comprehensive, would provide a database given that PPE is mandatory in many locations, would simplify PPE administration, would allow remote access to clinical data, and would provide the much-needed data for prospective studies in this area.
    Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 11/2014; 24(6):442-7. DOI:10.1097/JSM.0000000000000168 · 1.50 Impact Factor
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    ABSTRACT: Abstract Sex and gender differences in the cardiovascular adaptation to spaceflight were examined with the goal of optimizing the health and safety of male and female astronauts at the forefront of space exploration. Female astronauts are more susceptible to orthostatic intolerance after space flight; the visual impairment intracranial pressure syndrome predominates slightly in males. Since spaceflight simulates vascular aging, sex-specific effects on vascular endothelium and thrombotic risk warrant examination as predisposing factors to atherosclerosis, important as the current cohort of astronauts ages. Currently, 20% of astronauts are women, and the recently selected astronaut recruits are 50% women. Thus there should be expectation that future research will reflect the composition of the overall population to determine potential benefits or risks. This should apply both to clinical studies and to basic science research.
    Journal of Women's Health 11/2014; 23(11):950-5. DOI:10.1089/jwh.2014.4912 · 1.90 Impact Factor
  • William K Cornwell, Benjamin D Levine
    10/2014; DOI:10.1016/j.jchf.2014.10.006
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    ABSTRACT: Increasing participation in ultramarathons and other ultra-endurance events amplifies the potential for serious medical issues during and immediately following these competitions. Since these events are often located in remote settings where access may be extremely limited; the diagnostic capabilities, treatment options, and expectations of medical care may differ from those of urban events. This work outlines a process for assessment and treatment of athletes presenting for medical attention in remote environments, with a focus on potentially serious conditions such as major trauma, acute coronary syndrome, exertional heat stroke, hypothermia, hypoglycemia, exercise-associated hyponatremic encephalopathy, severe dehydration, altitude illness, envenomation, anaphylaxis, and bronchospasm. A list of suggested medical supplies is provided and discussed. But, given that diagnostic and treatment options may be extremely limited in remote settings, it is important for medical providers to understand how to assess and manage the most common serious medical issues with limited resources, and to be prepared to make presumptive diagnoses when necessary.
    Sports Medicine 10/2014; 45(2). DOI:10.1007/s40279-014-0270-y · 5.32 Impact Factor
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    ABSTRACT: Abnormal heart rate recovery (HRR) after maximal exercise may indicate autonomic dysfunction and is a predictor for cardiovascular mortality. HRR is attenuated with ageing and in middle-age hypertensive patients but it is unknown if HRR is attenuated in older-age adults with hypertension. This study compared HRR between 16 unmedicated Stage 1 hypertensive (HTN) participants (9M/7F; 68±5 [SD] yrs; awake ambulatory blood pressure [BP] 149±10/87±7mmHg) and 16 normotensive (CON) participants (9M/7F); 67±5 yrs; 122±4/72±5mmHg). Heart rate (HR), BP, oxygen uptake (VO2), cardiac output (Qc) and stroke volume (SV) were measured at rest, at two steady state work rates and graded exercise to peak during maximal treadmill exercise. During 6 minutes of seated recovery the change in HR (ΔHR) was obtained every minute and BP every 2 minutes. In addition HRR and R-R interval (RRI) recovery kinetics were analyzed using a mono-exponential function and the indexes (HRRI and RRII) were calculated. VO2max, HRmax, Qc and SV responses during exercise were not different between groups. ΔHR was significantly different (P<0.001) between the HTN group (26±8) and the CON group (36±12 beats.min(-1)) after 1 min of recovery but less convincing at 2 min (P=0.055). BP recovery was similar between groups. HRRI was significantly lower (P=0.016) and there was a trend of lower RRII (P=0.066) in the HTN group when compared to the CON group. These results show that in older-age adults, HRR is further attenuated with the presence of hypertension, which may be attributable to an impairment of autonomic function.
    Journal of Applied Physiology 10/2014; 117(11). DOI:10.1152/japplphysiol.00395.2014 · 3.43 Impact Factor
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    ABSTRACT: Background—It is unclear if, and to what extent, the striking cardiac morphologic manifestations of endurance athletes are a result of exercise training or a genetically determined characteristic of talented athletes. We hypothesized that prolonged and intensive endurance training in previously sedentary healthy young individuals could induce cardiac remodeling similar to that observed cross-sectionally in elite endurance athletes. Methods and Results—12 previously sedentary subjects (29􀁲6 yr; 7 men and 5 women) trained progressively and intensively for 12 months such that they could compete in a marathon. Magnetic resonance images for assessment of right and left ventricular mass and volumes were obtained at baseline and after 3,6,9, and 12 months of training. Maximum oxygen uptake (VO2max) and cardiac output at rest and during exercise (C2H2 rebreathing) were measured at the same time periods. Pulmonary artery catheterization was performed before and after 1 year of training, and pressure/volume and Starling curves were constructed during decreases (lower body negative pressure) and increases (saline infusion) in cardiac volume. Mean VO2max rose from 40.3􀁲1.6 to 48.7􀁲2.5 ml/kg/min after 1 year (p<0.00001), associated with an increase in both maximal cardiac output and stroke volume. Left and right ventricular mass increased progressively with training duration and intensity and reached levels similar to those observed in elite endurance athletes. In contrast, LV volume did not change significantly until six months of training, though RV volume increased progressively from the outset; Starling and pressure/volume curves approached, but did not match those of elite athletes. Conclusions—One year of prolonged and intensive endurance training leads to cardiac morphologic adaptations in previously sedentary young subjects similar to those observed in elite endurance athletes; however it is not sufficient to achieve similar levels of cardiac compliance and performance. Contrary to conventional thinking, the left ventricle responds to exercise with initial concentric not eccentric remodeling during the first 6-9 months after commencement of endurance training depending on the duration and intensity of exercise. Thereafter, the left ventricle dilates and restores the baseline mass to volume ratio. In contrast, the right ventricle responds to endurance training with eccentric remodeling at all levels of training.
    Circulation 10/2014; DOI:10.1161/CIRCULATIONAHA.114.010775 · 14.95 Impact Factor

Publication Stats

8k Citations
2,165.20 Total Impact Points

Institutions

  • 1991–2015
    • University of Texas Southwestern Medical Center
      • • Department of Internal Medicine
      • • Division of Cardiology
      • • Institute for Exercise and Environmental Medicine
      Dallas, Texas, United States
    • Duke University
      Durham, North Carolina, United States
  • 1994–2014
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2013
    • Brigham and Women's Hospital
      • Division of Sleep Medicine
      Boston, MA, United States
    • Indiana University Bloomington
      • Department of Kinesiology
      Bloomington, Indiana, United States
  • 2010–2012
    • Texas Health Resources
      Southlake, Texas, United States
  • 2011
    • John Peter Smith Hospital
      Fort Worth, Texas, United States
  • 1999–2010
    • New York Presbyterian Hospital
      New York, New York, United States
    • Uniformed Services University of the Health Sciences
      • Department of Family Medicine
      Maryland, United States
  • 2007
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 2006
    • Qinghai University
      Hsi-ning-shih, Qinghai Sheng, China
    • University of Southern California
      • Department of Biomedical Engineering
      Los Angeles, CA, United States
  • 2004–2006
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
    • National Sports Medicine Institute
      Лизбург, Virginia, United States
    • Nihon University
      Edo, Tōkyō, Japan
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 2005
    • Helen Hayes Hospital
      West Haverstraw, New York, United States
  • 2002
    • University of Texas at Arlington
      Arlington, Texas, United States
    • Pennsylvania State University
      • Department of Kinesiology
      University Park, MD, United States
    • Michigan Technological University
      • Department of Biomedical Engineering
      Houghton, MI, United States
    • Bethesda Hospital
      Jogjakarta, Daerah Istimewa Yogyakarta, Indonesia
  • 2001
    • University of Oslo
      Kristiania (historical), Oslo County, Norway
  • 1992–1994
    • IT University of Copenhagen
      København, Capital Region, Denmark