The Importance of Exercise Testing in Occupational Cardiovascular Assessment for High-Hazard Professions

Rebecca R. Chamley, MBBS, BSc; David A. Holdsworth MA DPhil; Oliver J. Rider BA BMBCh FRCP DPhil; Edward D. Nicol, MD FRCP FRCR FESC FACC DAvMed

Disclosures

Eur Heart J. 2019;40(37):3078-3080. 

In the setting of high-hazard work, occupational medicine is principally concerned with risk assessment. Cardiovascular risk assessment must consider interactions of the body with the environment of the work in order to accurately estimate event rates. Aircrew, emergency service workers, and miners, for example, face heterogeneous physiological and psychological challenges including hypoxia, sustained acceleration, thermal stress, high physical workload, disorientation, fear and sensory overload. One can readily appreciate how these environmental factors might influence cardiac output, increase myocardial oxygen demand, lead to electrolyte shifts, and alter the balance of autonomic activity, such that the threshold for arrhythmia, ischaemia, and acute heart failure is reduced. Furthermore, the effects of specific therapies: drugs, devices, coronary stenting and ablation must also be considered in the context of occupational role and environmental exposure.

It is difficult to faithfully reproduce all occupational stressors for environment-specific testing. Increasingly impressive high-fidelity training simulators are available, including 'human centrifuges' that can achieve the extreme, prolonged accelerations experienced in high-performance aircraft (Figure 1), or environmental and hypobaric chambers that can reproduce extremes of temperature and pressure. Though such hi-fidelity simulators provide the best substitute for the actual environment, their complexity and expense limits their availability. Furthermore, the practical physical challenges of such environments can make extensive physiological assessment challenging. Although exercise-stress cannot exactly reproduce all environmental extremes of a high-hazard profession, it does place the heart, lungs and circulatory system under considerable load and is an important surrogate for other forms of environmental stress.

Figure 1.

The Royal Air Force Human centrifuge in the UK (Panel A) is used to simulate high fidelity military air combat sorties, whilst also allowing simultaneous physiology assessment to be undertaken. Wearing full life support systems, sorties that include sustained acceleration (Panel B) of up to +15 Gz are possible in these modern systems, placing significant strain on the cardiovascular and respiratory systems.

At peak exercise, cardiac output can rise to 40 L/min and ventilation to 200 L/min; approximately 8- and 20-fold increases from the resting condition. Blood flow to skeletal muscle, which typically has a low flow rate at rest, can increase 100-fold.[1] Furthermore, dramatic shifts in extracellular potassium are seen with high-intensity exercise. Within seconds of reaching peak workload, plasma potassium typically reaches ~8 mmol/L, and on stopping exercise, potassium levels fall to just below normal resting level just as rapidly, resulting in potassium shifts of 3–4 mmol/L in just 1–2 min.[2] There are three important conclusions that may be drawn from this remarkable plasticity in human metabolic capacity and the associated electrolyte shifts.

  1. Activities, including occupational work, which are associated with high-intensity exercise will place huge demands on the lungs, heart, circulation, gas-carriage capacity of blood, metabolism, and musculoskeletal system.

  2. Measurements of the cardiovascular system performed at rest are not sufficiently sensitive to uncover cardiorespiratory abnormalities which may cause a limitation only at high workload.

  3. The demonstration of high exercise capacity provides robust reassurance that there is no significant abnormality in the airway, respiratory membrane, pulmonary circulation, cardiac function, blood, systemic circulation, metabolism, or skeletal muscle. In other words, if the exercise capacity is unequivocally normal, there is no major deficiency anywhere on the pathway of oxygen, from mouth to mitochondrion.

Work in exercise physiology and exercise testing reveals that the presence of a high exercise capacity, regardless of symptoms, electrocardiogram (ECG) changes and underlying coronary anatomy, confers an excellent prognosis, even in the presence of significant coronary artery disease (Table 1). Where the functional capacity is reduced, the pattern of exchange of respiratory gases at the mouth, combined with ventilation, heart rate and external work developed can be analysed to uncover characteristic patterns and so identify the location of the deficit. This pattern-recognition underlies the practice of cardiopulmonary exercise testing (CPET).

Numerous large studies have linked activity levels assessed by questionnaire to all-cause mortality. These include the Framingham study,[3] Harvard Alumni study,[4] and Multiple Risk Factor Intervention Trial.[5]

More importantly, from the perspective of the cardiologist addressing individual cardiovascular risk, there is robust evidence that objective measurements of cardiorespiratory fitness are strongly associated with clinical outcome. Myers et al determined the exercise capacity of 6213 men referred for treadmill exercise test and followed them up for a median 6.2 years, with a primary endpoint of all-cause mortality.[6] A total of 3679 patients had either a history of cardiovascular disease or an abnormal exercise test; 2534 had both a normal exercise test and no cardiovascular disease history. The annual mortality rate was 2.6%. After adjustment for age, the strongest predictor of death in both groups was peak exercise capacity (in metabolic equivalents: METs). This parameter outperformed smoking, hypertension, history of diabetes, left ventricular hypertrophy, history of heart failure, history of myocardial infarction, ST segment depression, body mass index, and cholesterol. To demonstrate the magnitude of effect, each additional MET (1 MET ≡ metabolic activity at rest) was associated with a 12% increase in survival. In every risk-factor subgroup, the risk of death associated with achieving <5 METs peak exercise capacity was approximately double that of >8 METs.[6]

The assessment of coronary disease in high hazard populations and the use of population-based risk estimation tools has been previously considered in this series.[7,8] Risk profiling is based upon population data and the prediction of risk for an individual is a crude estimate. Exercise testing permits an individualised assessment (Table 1).

It is plausible that a high level of fitness and low risk of cardiovascular events are parallel results of heritable traits, rather than being causally related. However, a large Swedish study of 5200 pairs of monozygotic twins demonstrated 20% all-cause and 30% cardiovascular mortality reduction in twins who were more physically active than their genetically identical sibling.[7] The occupational implication of these observations is that, regardless of the presence of occult coronary disease, if resting left ventricular function is normal, a high exercise capacity without ECG changes, signals an excellent prognosis and low likelihood of cardiovascular events. It is likely that, where the maximal exercise capacity—a cheap and reproducible parameter to obtain—is not integrated into risk assessment, that fitter older workers are being unnecessarily excluded, and conversely that some unfit, unhealthy younger workers, are being passed as fit, based on a falsely reassuring population-estimate of their cardiovascular risk.

A key output of exercise testing in occupational cardiology therefore is in the prognostic reassurance of high exercise capacity, which can be established by CPET or exercise treadmill test. However, the additional diagnostic benefit available from CPET is relevant when the exercise capacity is less than normal. In these circumstances, pattern analysis of the O2 uptake, CO2 elimination, ventilation, ECG, heart rate, and external workload can be used to localize the functional limitation within the ventilatory system or circulatory system (including impaired peripheral oxygen delivery and impaired mitochondrial metabolism and oxygen uptake). Indeed, CPET is recommended (IIa, C) by the European Society of Cardiology (ESC) in the assessment of unexplained breathlessness.[8]

Maximum oxygen uptake (CPET) has been used to discriminate pathological ventricular hypertrophy from athletic adaptation.[9] A similar diagnostic quandary exists with the finding of borderline chamber dilatation and mild reduction in ejection fraction. This phenotype may be seen in either athletic adaptation or incipient cardiomyopathy and may prove difficult to distinguish even with the use of cardiovascular magnetic resonance imaging.[10] Peripheral oxygen extraction is remarkably consistent between individuals, during both rest and stress. As a result, VO2/heart rate: 'VO2 pulse', reflects stroke volume. CPET parameters may therefore reveal differences in cardiopulmonary response to exercise between early cardiomyopathy and athletic adaptation, which are indistinguishable by imaging performed at rest.

The American Society of Echo guidelines likewise recognize that the challenge of diagnosing early diastolic dysfunction and suggest the use of diastolic stress testing, by focused exercise echo, in borderline cases.[11] The expected finding of a lowering in E/e' with exercise stress in a healthy heart contrasts with a rise in this parameter with diastolic dysfunction. Measurement of E/e' at rest and stress increases the sensitivity of detecting diastolic dysfunction, permitting earlier detection of heart muscle disease. Exercise testing also permits both reassurance regarding abnormalities identified at rest, such as appropriate shortening of the PR or QTc interval, or the suppression of ventricular ectopy, and the exposure of problems, which are not manifest at rest, such as the development of exertional heart block, or failure to demonstrate a normal blood pressure response.

The scope of human functional capacity is very wide. Achieving a high level of physical work, combined with a normal pattern of blood pressure, heart rate and ventilatory responses, to reach a high peak oxygen uptake is a cheap, safe and reproducible way to demonstrate the body's ability to withstand a variety of environmental stressors. Likewise, investigation of human physiology during maximal exertion can uncover many abnormalities which are hidden at rest. Anatomic assessment alone, is insufficient to provide the required evidence to support many occupational health decisions and physiological assessment should always be considered to inform comprehensive cardiovascular assessment in those undertaking high hazard occupations.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....