Exercise Dose Associated With Military Service: Implications for the Clinical Management of Inherited Risk for Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

Introduction

High levels of aerobic exercise in individuals who have a gene mutation associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with clinical disease progression. Guidelines consequently restrict patients from competitive athletics. However, there is minimal literature to guide the safe dosing of physical activity outside of the setting of competitive athletics. Patients may be physically active pursuant to a variety of careers, including military service. This study aimed to define a therapeutic window for exercise for ARVC gene-positive individuals that are compatible with continuing military service and general health while maintaining a level of exercise below that which risks disease progression.

Materials and Methods

Using standard metabolic equations, we calculated the minimum VO₂ max (amount of oxygen utilized at peak exercise capacity) required to pass the physical fitness tests for each branch. We then developed a sample exercise prescription to maintain this level of fitness. We compared the prescribed exercise load with the physical activity levels associated with non-inferior clinical outcomes in ARVC gene-positive individuals. Additionally, we determined the physical activity exposure sustained by service members based on self-report data and compared these values with the upper limit of safe exercise exposure.

Results

Based on a review of the currently available literature, aerobic exercise exposure less than 700 to 1,100 MET-hours/year (metabolic equivalent-hours per year) is not associated with inferior clinical outcomes for gene-positive individuals. A military service member needs 600 to 700 MET-hours/year to minimally pass the physical fitness test. However, many military members are exercising in excess of this minimum, with typical exposures between 900 and 2,400 MET-hours/year.

Conclusions

A therapeutic window of aerobic exercise may exist for ARVC gene-positive individuals which would allow continuation of military service while maintaining levels of exercise restriction associated with non-inferior clinical outcomes.

INTRODUCTION

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic condition which predisposes individuals to ventricular arrhythmias and dilated cardiomyopathy. Affected individuals may present with palpitations, syncope, chest pain, dyspnea, and sudden cardiac death. However, ARVC may remain asymptomatic, with some patients presenting for care only after the diagnosis of a family member.

For individuals with genotype-positive phenotype-positive ARVC (“G+ P+,” ie subjects having evident conditions meeting Task Force Criteria¹), exercise is associated with negative clinical outcomes including decreased right ventricular ejection fraction and ventricular arrhythmias.² For genotype-positive phenotype-negative individuals (“G+ P–,” ie subjects with a pathogenic mutation but no clinical manifestation of disease), endurance exercise is associated with clinical progression to an ARVC phenotype.^3,4 Current guidelines are conflicted, especially regarding G+ P– individuals. A review of guidelines over the past 5 years shows a wide variety of guidance including a range of acceptable exercise exposure for G+ P+ individuals and counselling G+ P– individuals that frequent exercise exposure is associated with increased risk of progression to disease without delineating a safe exercise dose.^5,6 Exercise prescriptions can be given in a MET-hour/year format. A MET, or metabolic equivalent, is a unit of measure which quantifies physical activity intensity in comparison with sitting, resting quietly (1 MET or 3.5 mL/kg/min of oxygen). Walking at 3 miles per hour is 3 METs and running at 6 miles per hour is 10 METs.⁷ Based on a review of the currently available literature, aerobic exercise exposure less than 700 to 1,100 MET-hours/year is not associated with inferior clinical outcomes for G+ P+ individuals.^2,3,5,6,8,9

Individuals may be physically active pursuant to a profession such as military service. An individual’s level of physical fitness can be measured with VO₂ max (the amount of oxygen consumed at peak aerobic effort). Currently, there is minimal guidance regarding the safe exercise dose that would allow for the appropriate restriction of physical activity below the ARVC “danger zone” while permitting patients the maximal benefit of exercise as well as maximizing aerobic capacity to facilitate the continuation of daily physical activities, including military service. The aim of this study is to establish the exercise dosage associated with active duty military service to determine if service members who are found to be G+ P– may remain on active duty without exceeding the maximum recommended exercise levels.

METHODS

We reviewed the literature for data regarding physical activity levels of active duty service members and both G+ P+ and G+ P– ARVC patients utilizing PubMed as the primary search engine. Search terms included “arrhythmogenic right ventricular cardiomyopathy, ARVC, exercise prescription, exercise, sudden cardiac death, arrhythmia, exercise exposure, military, Army, Navy, Air Force.” A proxy for the minimum required physical activity for military retention was calculated by applying established metabolic conversion equations to the minimum VO₂ max (expressed in METs) required to pass the service-specific physical fitness test. ^7,10 We then developed a sample exercise prescription to achieve this minimum required maximal aerobic capacity using accepted practices (see Fig. 1). ⁷ We obtained self-reported physical activity levels of service members from the 2011 Health Related Behaviors Survey of U.S. Active Duty Military Personnel¹¹. The appropriate exercise dose in G+ P– was extrapolated from studies primarily examining disease progression in G+ P+; the safe exercise dose proposed represents a level of exercise below which there is no demonstrated association with progression of arrhythmias or ventricular dysfunction in G+ P+. ^{2 8} Although some studies reported physical activity in MET-hours, other studies reported activity in hours per given time period and intensity (ie moderate versus strenuous). The latter were converted to a MET-hour/year format using accepted metabolic equations and equivalents.⁷ Additionally, calculated values of safe exercise exposure were compared with MET-hour exposure associated with an experimental training program designed to increase service member performance on a weighted pack carry.¹²

FIGURE 1.

Sample Calculations.

RESULTS

Our literature review yielded almost exclusively data on exercise dosage in G+ P+ individuals, with a small subset of data on G+ P– individuals (Table I). Safe exercise dose (not associated with clinically inferior outcomes) ranged between 720 and 1,100 MET-hours/year depending on outcome measured (arrhythmias versus right ventricular function).^2,8 A small observational study of G+ P– individuals found that patients who exercised 650 MET-hours/year (the American Heart Association guideline suggested amount of physical activity for the general adult population¹³) did not have an increased risk of disease progression and had no episodes of either ventricular tachycardia or ventricular fibrillation. Conversely, patients with these complications incurred 1,787 to 2,275 MET-hours/year.⁵ Individuals require a minimum aerobic stimulus of at least 45% VO₂ max to increase VO₂ max.¹⁴ If an 18-year-old Army male (the demographic with the highest minimum MET output requirement) was trying to maintain the minimum cardiovascular fitness in order to pass his fitness test, he could run his test distance (a 2-mile run) at approximately an 8-minute/mile three times weekly to train. This is the pace required to pass the run portion of the test and a sufficient aerobic stimulus to maintain his physical fitness. This prescription incurs 48 minutes of physical activity at 13 METs per week or an annual exercise exposure of 540.8 MET-hours/year. This calculation was applied to the other services and age requirements and compared to the ARVC safe exercise dose literature (Fig. 2).

TABLE I.

Exercise Exposure and Associated Clinical Outcomes

Study	Target Population	MET-hours/year	Endpoint
Saberniak et al.2	G+ P+ (59%) and G+ P– family members (41%)	728	Increased dilation of right ventricle
		1,020	Increased risk of arrhythmia
Sawant et al.5	G+ P–	650	No increased risk of progression to G+ P+ and/or arrhythmia
		1,787	Average annual exposure at time of transition to G+ P+
		2,275	Average annual exposure at time of first ventricular tachycardia or ventricular fibrillation
Wang et al.8	G+ P+ with ICDs	1,100	Average annual exercise exposure of patients who reduced exercise after diagnosis, which is associated with decreased risk of appropriate first ICD discharge

FIGURE 2.

Exercise Dose in MET-Hours/Year Needed to Pass the Run Portion of the Service-specific Physical Fitness Test, Separated by Service and Sex. The Bar Represents the Variability of Associated Dose Given Different Standards for Different Age Groups. 650 MET-Hour/Year (green) is the AHA Recommended Amount of Exercise for the General Population and is not Associated with Progression in G+ P– Individuals. 5,720 MET-Hour/Year (Yellow) is not Associated with Increased Dilation in G+ P+ Individuals. 21,100 MET-Hour/Year (Blue) is the Exercise Dose Associated with Training Program Developed to Improve Performance in a Weighted Carry Task. 121,787 MET-Hour/Year (Red) is Annual Exposure Associated with Progression from G+ P– to G+ P+ 0.5.

However, minimum required exposure does not necessarily correlate with actual exposure to physical activity. Military service is associated with a significant level of exercise exposure each year, with the highest exposure levels found in the Army and Marine Corps per self-report data (Fig. 3). All branches of military service were associated with enough exercise exposure to classify members as athletes as defined by the current ARVC-focused literature (ie at least 3 hours per week of moderate to intense dynamic activity, of at least 6 METs, or at least 936 MET-hours/year).⁸ Both the Army and Marine Corps had individuals exceeding the dose of exercise associated with increased arrhythmia in G+ P+ individuals. ⁸ Some service members are registering extremely high levels of physical activity associated with disease progression in G+ P– individuals, although the range of activity also includes an exercise dose that is associated with fewer arrhythmic events. ⁸

FIGURE 3.

Exercise Exposure in MET-Hours/Year by Service. Values were Calculated from Self-report Data. [10] 650 MET-Hour/Year (Green) is the AHA Recommended Amount of Exercise for the General Population and is not Associated with Progression in G+ P– Individuals. 5,720 MET-Hour/Year (Yellow) is not Associated with Increased Dilation in G+ P+ individuals. 21,100 MET-Hour/Year (blue) is the Exercise Dose Associated with Training Program Developed to Improve Performance in a Weighted Carry Task. 121,787 MET-Hour/Year (Red) is Annual Exposure Associated with Progression from G+ P– to G+ P+0.5.

Previous studies have proposed exercise regimens designed to improve performance on the Army Physical Fitness test and military-specific tasks such as a weighted carry. Analysis of one such program¹² did not exceed the upper limit of safe exercise dose. Service members enrolled in an experimental exercise training routine including aerobic and strength components (including long distance running, sprints, and weightlifting) for a 12-week program. Participants were on average exposed to 15.2 MET-hour/week of cardiovascular stimulus and 3 MET-hour/week of weight training stimulus, for a total of 18.2 MET-hour/week. With this dosage of exercise, they were able to improve performance on a 2 mile load-bearing task by 14%.¹² Extending the program from 12 weeks to a full year would expose service members to 1,005.3 MET-hour/year, within the range of suggested safe exposure for G+ P+, and well below the dose associated with increased arrhythmic events in G+ P– individuals (1,820 MET-hour/year). This exercise program that was developed for improved performance on military-specific activities for the general military population without consideration for clinically necessitated exercise restriction may still be compliant with a safe exercise prescription for G+ P– individuals.

DISCUSSION

Exercise dosage associated with military service is significant enough to qualify most service members as athletes yet is also characterized by high variability. Minimum exercise required to pass the service-specific fitness tests requires a relatively low exercise exposures and are completely compatible with safe levels of exercise for G+ P– individuals. Most branches require less than the most conservative estimates of safe exercise allowances even for patients with manifest ARVC disease (G+ P+) (720–1,100 MET-hours/year). Notably, the Marine Corps’ 3 mile run in contrast to the 2 or 1.5 mile run does require an exercise dose which would exceed the safe dose for a G+ P+ individual. All branches fall far below the 1,820 MET-hour/year dosage associated with inferior clinical outcomes in G + P- individuals. Active duty service members identified as G+ P– can continue to meet minimum fitness requirements for service while maintaining clinically appropriate exercise restrictions. However, a review of self-report data shows that most service members exercise in excess of these minimum requirements. Therefore, careful communication between doctor and patient is required to ensure adherence to an appropriate exercise prescription. Because military service is a culture which promotes copious physical activity, continuation in the services with a prescription for reduced exercise will take mindful recognition of the patient’s physical activity level to continue to meet service-specific requirements. Although G+ P- would be able to meet the minimum physical fitness requirements for general military retention, it is likely that they would be unable to appropriately meet the demands of the more physically demanding careers (eg infantry) and should be limited from these positions. However, critical military positions and skillsets do not always require high physical activity (eg intelligence analysis). This should be a carefully individualized decision, made through joint decision-making with the patient, their command, and the physician who has a thorough understanding of ARVC, exercise, and military requirements. Importantly, the military’s focus has traditionally been on standardization. The future challenge lies in adaption to personalization in the upcoming era of personalized medicine. ARVC G+ P– state is just one of the myriad of genetic vulnerabilities that service members will be diagnosed with as precision medicine expands. This study comes near the beginning of a broader discussion that must be had.

Although our calculations pertain to active duty service members, this work also has ramifications for civilian G+ P– individuals. Data from several studies suggest that the safe exercise exposure limit is high enough that G+ P– individuals should be allowed to maintain relatively high cardiovascular fitness through exercise (maintaining VO₂ max at approximately 14 METs falls within safe exercise exposure parameters). G+ P– individuals can engage in regular cardiovascular exercise (eg running 2 miles three times weekly at an 8-minute/mile pace). This allows these patients to continue to experience the benefits of aerobic exercise while mitigating the risk associated with G+ P– state.

Active duty G+ P– and G+ P+ individuals represent a small portion of all military members. In the general population, the incidence of ARVC estimated between 1:1,000 and 1:5,000.^15,16 The average age of diagnosis is 29 and accounts for 22% of sudden cardiac death in certain populations of athletes.¹⁶ It is most likely underdiagnosed in the United States, and the prevalence in the military has not been quantified in the literature.¹⁶ However, with an average age between 25 and 29 depending on branch, service members may present for diagnosis and treatment during an active duty career.¹⁷ Additionally, there is evidence that high levels of exercise such as those incurred by service members may predispose individuals to ARVC even without predisposing genetic factors.¹⁸ A better understanding of ARVC and mitigation strategies within the constructs of military service is important to improve clinical outcomes in this at-risk population. Additionally, there are several other conditions which demand exercise restriction (eg myocarditis). It is important to accurately measure the exercise dose associated with active duty military service to allow for evidence-based recommendations in these clinical scenarios.

The current data support that some aerobic exercise is safe for G+ P– patients, and therefore the finding of a pathogenic mutation is not universally incompatible with military service. However, these conclusions are based on calculated data from the physical fitness tests and self-report data, which are commonly inaccurate.¹⁹ An important next step is to directly measure (eg using an activity tracker) how much exercise exposure is actually associated with military service. Finally, because the safe dosage of physical activity was also determined using self-report data, it will also be important to further explore the safe limit of physical activity for G+ P– using some form of direct measurement, as well.

There are several key limitations to this work. First, the studies used to determine safe exercise dosage were small, and the G+ P– patients made up only a portion of this population. Additionally, service-specific fitness tests were used as a proxy for the minimum physical fitness level required for retention. Although every service member is required to pass the test, the test may not represent a true minimum. Even low physical activity military occupation service designations may require increased amounts of non-exercise-associated physical activity while conducting operations in a deployed environment. For example, a linguist may be called on to help set up tents or other demanding tasks, as needed. Therefore, it is important to note that the findings in this study need to be interpreted with the understanding that the service member would also need to limit non-exercise activity, an understanding that would require open communication with the service member’s chain of command to ensure that the restriction is respected. In fact, one study of exercise exposure during basic training suggests that a trainee spends more time engaged in non-exercise physical activity such as marching, than physical activity designed to improve fitness, as is measured in the calculations.²⁰ Furthermore, the Army has proposed moving to a new “combat fitness test” with expanded tasks such as a sled drag and deadlift. Given the increased number of components, it is likely that soldiers may need to further increase their physical activity above and beyond the exercise needed to pass the current physical fitness test.²¹ A service member identified as a G+ P– may necessitate a medical evaluation board (MEB) to determine if a service member with these restrictions is worldwide deployment-qualified and employ appropriate restriction codes if this is not the case. Following MEB evaluation, the service member should be evaluated by the physical evaluation board (PEB) to determine if an individual with the given restrictions is appropriate for military retention. This decision should be made by balancing the needs of the military and the specific nature of the service member’s skill identifier (occupation). Approach to the MEB should include a physician who is familiar with the current literature and exercise requirements for ARVC.

Self-report data was used to quantify the actual exercise dose experienced by service members, which, as noted, is often inaccurate.¹⁹ Both exercise and non-exercise-associated physical activity are overestimated, with variations in self-report tools. Exercise estimates based on self-report data are more accurate than non-exercise-associated physical activity but still exhibit significant discordance with measured activity.

CONCLUSION

Although G+ P+ individuals cannot continue military service because of the increased risk for sudden death, G+ P– individuals are not precluded from military service fitness requirements. A careful, personalized risk/benefit profile for each patient should be constructed when such an individual is identified. It is possible for a G+ P– service member to maintain the relatively high level of physical fitness required for military retention while conforming with clinically appropriate exercise restriction. Further research is needed to better quantify both the safe dose of exercise for these individuals as well as the exercise dose associated with military service using direct measurement.

Collaborative Health Initiative Research Program and Military Cardiovascular Outcomes Research F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD Department of Medicine Division of Cardiology, Uniformed Services University of the Health Sciences Bethesda, MD 20814. The views expressed in this manuscript are those of the author and do not reflect the official policy of the Department of Army, Navy, Air Force, Department of Defense, the Uniformed Services University, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., or the U.S. Government. Data in this manuscript were previously presented as a poster at the 2019 Military Health Systems Research Symposium.

Funding: Partial funding from NHLBI Grant: IAA-A-HL-007.001 and HU00011920029 from the Defense Health Agency.