Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular Remodeling

Scott, Jessica M.; Martin, David S.; Ploutz‐Snyder, Robert; Downs, Meghan; Dillon, E. Lichar; Sheffield‐Moore, Melinda; Urban, Randall J.; Ploutz‐Snyder, Lori L.

doi:10.1249/mss.0000000000001619

Cited by 12 publications

(9 citation statements)

References 41 publications

(50 reference statements)

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“…For example, reduced strain and strain rate revealed impaired myocardial function prior to LVEF decline [38] in cancer patients treated with anthracycline-containing therapy. Thus, evaluation of cardiac and vascular function with advanced imaging techniques at rest [39], as well as responses to a peak cardiopulmonary exercise test [40], may provide important insight into characterizing the ‘cachectic heart’.…”

Section: Discussionmentioning

confidence: 99%

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial

et al. 2019

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Background Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; however, the effects of testosterone on cardiac morphology and function are unknown. Accordingly, as an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction. Methods Men and women recently diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or concurrent chemoradiation were administered an adjunct 7 week treatment of weekly intramuscular injections of either 100 mg testosterone (T, n = 1 M/5F) or placebo (P, n = 6 M/4F) in a double-blinded randomized fashion. LV morphology (wall thickness), systolic function (ejection fraction, EF), diastolic function (E/A; E’/E), arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were assessed. Results No significant differences were observed in LV posterior wall thickness in placebo (pre: 1.10 ± 0.1 cm; post: 1.16 ± 0.2 cm; p = 0.11) or testosterone groups (pre: 0.99 ± 0.1 cm; post: 1.14 ± 0.20 cm; p = 0.22). Compared with placebo, testosterone significantly improved LVEF (placebo: − 1.8 ± 4.3%; testosterone: + 6.2 ± 4.3%; p < 0.05), Ea (placebo: 0.0 ± 0.2 mmHg/mL; testosterone: − 0.3 ± 0.2 mmHg/mL; p < 0.05), and Ea/Ees (placebo: 0.0 ± 0.1; testosterone: − 0.2 ± 0.1; p < 0.05). Conclusions In patients with advanced cancers, testosterone was associated with favorable changes in left ventricular systolic function, arterial elastance, and ventricular-arterial coupling. Given the small sample size, the promising multisystem benefits of testosterone warrants further evaluation in a definitive randomized trial. Trial registration This study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009). Electronic supplementary material The online version of this article (10.1186/s12885-019-6006-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial

et al. 2019

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“…Efforts to leverage multiple types of data to personalize the prescription of exercise and diet interventions are illustrative. For example, the National Aeronautics and Space Administration (NASA) has examined the applicability of deep phenotyping to prescribe tailored doses and types of exercise interventions to mitigate the cardiovascular impact of long space travel. In addition, Zeevi et al have used clinical deep phenotyping with multidimensional data in conjunction with machine‐based learning to personalize the specific components of diet interventions .…”

Section: Developing a Blueprint For Implementation In The United Statesmentioning

confidence: 99%

Implementing personalized pathways for cancer follow‐up care in the United States: Proceedings from an American Cancer Society–American Society of Clinical Oncology summit

Alfano

Mayer

Bhatia

et al. 2019

CA A Cancer J Clinicians

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A new approach to cancer follow‐up care is necessary to meet the needs of cancer survivors while dealing with increasing volume and provider shortages, knowledge gaps, and costs to both health care systems and patients. An approach that triages patients to personalized follow‐up care pathways, depending on the type(s) and level(s) of resources needed for patients’ long‐term care, is in use in the United Kingdom and other countries and has been shown to meet patients’ needs, more efficiently use the health care system, and reduce costs. Recognizing that testing and implementing a similar personalized approach to cancer follow‐up care in the United States will require a multipronged strategy, the American Cancer Society and the American Society of Clinical Oncology convened a summit in January 2018 to identify the needed steps to move this work from concept to implementation. The summit identified 4 key strategies going forward: 1) developing a candidate model (or models) of care delivery; 2) building the case for implementation by conducting studies modeling the effects of personalized pathways of follow‐up care on patient outcomes, workforce and health care resources, and utilization and costs; 3) creating consensus‐based guidelines to guide the delivery of personalized care pathways; and 4) identifying and filling research gaps to develop and implement needed care changes. While these national strategies are pursued, oncology and primary care providers can lay the groundwork for implementation by assessing their patients’ risk of recurrence and the chronic and late effects of cancer as well as other health care needs and resources available for care and by considering triaging patients accordingly, referring patients to appropriate specialized survivorship clinics as these are developed, helping to support patients who are capable of self‐managing their health, setting expectations with patients from diagnosis onward for the need for follow‐up in primary care and/or a survivorship clinic, and improving coordination of care between oncology and primary care.

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“…Indeed, the resultant deconditioning of numerous physiological systems and loss of strength, power, and cardiorespiratory fitness is well documented (Tesch et al, 2005; Lang et al, 2006; Trappe et al, 2009; Moore et al, 2010; Platts et al, 2014; Bloomberg et al, 2015). Exercise has long been used as the primary countermeasure for μG-induced deconditioning and the history of this has been detailed in an accompanying paper introducing this Research Topic (Scott et al, 2018). Recent reviews (Loenneke et al, 2012; Carpinelli, 2014) have also discussed the considerable attempts to solve the issue of how best to employ this countermeasure in μG environments.…”

Section: Introductionmentioning

confidence: 99%

“…A recent issue of Medicine and Science in Sports and Exercise detailed the results of NASA’s relatively recent 70-day bed rest study. This involved the use of concurrent resistance training and “cardio” exercise, in addition to testosterone supplementation, as countermeasures to deconditioning in a range of physiological systems (Cromwell et al, 2018; Dillon et al, 2018; Mulavara et al, 2018; Murach et al, 2018; Ploutz-Synder et al, 2018; Scott et al, 2018). The exercise interventions examined in the aforementioned bed rest study have been somewhat influenced by the recent body of literature supporting the use of high effort interval based “cardio” protocols [i.e., High Intensity Interval Training (HIIT)] as this was implemented as part of the concurrent program.…”

Section: Introductionmentioning

confidence: 99%

Comparisons of Resistance Training and “Cardio” Exercise Modalities as Countermeasures to Microgravity-Induced Physical Deconditioning: New Perspectives and Lessons Learned From Terrestrial Studies

Steele

Androulakis-Korakakis

Perrin

et al. 2019

Front. Physiol.

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Prolonged periods in microgravity (μG) environments result in deconditioning of numerous physiological systems, particularly muscle at molecular, single fiber, and whole muscle levels. This deconditioning leads to loss of strength and cardiorespiratory fitness. Loading muscle produces mechanical tension with resultant mechanotransduction initiating molecular signaling that stimulates adaptations in muscle. Exercise can reverse deconditioning resultant from phases of detraining, de-loading, or immobilization. On Earth, applications of loading using exercise models are common, as well as in μG settings as countermeasures to deconditioning. The primary modalities include, but are not limited to, aerobic training (or “cardio”) and resistance training, and have historically been dichotomized; the former primarily thought to improve cardiorespiratory fitness, and the latter primarily improving strength and muscle size. However, recent work questions this dichotomy, suggesting adaptations to loading through exercise are affected by intensity of effort independent of modality. Furthermore, similar adaptations may occur where sufficient intensity of effort is used. Traditional countermeasures for μG-induced deconditioning have focused upon engineering-based solutions to enable application of traditional models of exercise. Yet, contemporary developments in understanding of the applications, and subsequent adaptations, to exercise induced muscular loading in terrestrial settings have advanced such in recent years that it may be appropriate to revisit the evidence to inform how exercise can used in μG. With the planned decommissioning of the International Space Station as early as 2024 and future goals of manned moon and Mars missions, efficiency of resources must be prioritized. Engineering-based solutions to apply exercise modalities inevitably present issues relating to devices mass, size, energy use, heat production, and ultimately cost. It is necessary to identify exercise countermeasures to combat deconditioning while limiting these issues. As such, this brief narrative review considers recent developments in our understanding of skeletal muscle adaptation to loading through exercise from studies conducted in terrestrial settings, and their applications in μG environments. We consider the role of intensity of effort, comparisons of exercise modalities, the need for concurrent exercise approaches, and other issues often not considered in terrestrial exercise studies but are of concern in μG environments (i.e., O2 consumption, CO2 production, and energy costs of exercise).

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Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular Remodeling

Abstract: An integrated approach with evaluation of cardiac morphology, mechanics, V˙O2peak, and biomarkers provides extensive phenotyping of cardiovascular atrophic remodeling. Exercise training and exercise training with low-dose testosterone supplementation abrogates atrophic remodeling.

Cited by 12 publications

References 41 publications

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial

Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial

Implementing personalized pathways for cancer follow‐up care in the United States: Proceedings from an American Cancer Society–American Society of Clinical Oncology summit

Comparisons of Resistance Training and “Cardio” Exercise Modalities as Countermeasures to Microgravity-Induced Physical Deconditioning: New Perspectives and Lessons Learned From Terrestrial Studies

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