European Journal of Heart Failure

European Journal of Heart Failure 2008 10(2):112-118; doi:10.1016/j.ejheart.2007.12.011

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (3) Request Permissions Disclaimer Google Scholar Articles by Ingle, L. Search for Related Content PubMed PubMed Citation Articles by Ingle, L. Social Bookmarking          What's this?

© 2008 European Society of Cardiology

Prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure

Lee Ingle^*

Carnegie Faculty of Sport and Education, Leeds Metropolitan University Beckett's Park, Headingley, Leeds LS6 3QS, UK

	Abstract

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Cardiopulmonary exercise testing (CPET) is a well established technique for stratifying cardiovascular risk in patients with chronic heart failure (CHF). Important prognostic variables include a reduced peak oxygen uptake which has a central use in cardiac transplant selection, and the abnormal relation between minute ventilation (VE) and carbon dioxide production (VCO₂), often referred to as the elevated VE/VCO₂ slope. We will discuss the pathophysiology of these abnormal responses to exercise in CHF, and how these are interpreted during CPET. The potential of CPET for diagnosing circulatory, respiratory, metabolic, musculoskeletal or mixed limitations is an emerging field of research. We will speculate on how CHF manifests during CPET, and clarify the pathophysiological basis of these exercise responses. To improve our understanding of the diagnostic value of CPET, further investigation is required by clinicians to develop reference ranges for CHF patients from a co-ordinated multicentre approach. The use of CPET technology is becoming increasingly prevalent in cardiology services, and it is likely that, in the future, CPET will take a more prominent role in guiding patient management provision.

Key Words: Exercise testing • Risk stratification • CHF • CPET

Received August 2, 2007; Revised November 16, 2007; Accepted December 19, 2007

	1. Introduction

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Chronic heart failure (CHF) is a disorder associated with high mortality and persistent and prolonged hospitalizations, and affects >10 million people in the countries represented by the European Society of Cardiology [1]. The prevalence of CHF increases markedly with age and treatment and is often complicated by the presence of multiple co-morbidities. Patients' functional status and ultimately quality of life are impaired because the heart is unable to meet the demands of skeletal musculature, and symptoms manifest as signs of fatigue and dyspnoea. The pathophysiological basis of limited functional capacity has yet to be fully explained, however, abnormalities in central haemodynamic function are not sufficient to fully explain exercise intolerance in CHF because indices of resting ventricular function such as left ventricular ejection fraction (LVEF) are poorly correlated with peak exercise capacity [2].

Peripheral limitations such as a reduced quality of skeletal musculature including reduced bulk and consequent strength [3], and a higher preponderance of highly fatigable Type II muscle fibres [4] have been identified in CHF. This results in a greater production of metabolic products during exercise which will stimulate ergoreceptor activation. In turn, this will stimulate ventilatory drive and manifest as an increased ventilation relative to carbon dioxide production, thus increasing VE/VCO₂ slope and reducing PaCO₂ [5].

Objective assessment of exercise intolerance in CHF involves physical stress testing. The 6-min walk test (6-MWT) is commonly used, and is both reproducible and cheap to administer. It is useful in large patient populations, correlates with self-reported changes in symptoms over time [6] and is useful for risk stratification in CHF [7]. However, cardiopulmonary exercise testing (CPET), augmented with electrocardiography, blood pressure and heart rate responses provides far discriminatory data for a variety of functions. CPET guidelines have been published and regularly updated by working groups in cardiology in order to aid standardisation of test protocols, inform practice, and interpret exercise data [8-10].

	2. Practical considerations of CPET

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
CPET is a safe procedure with risk between 2 and 5 deaths per 100,000 tests performed [10]. Metabolic carts must be calibrated prior to the exercise test for linearity and gas volume according to manufacturer's instructions. Ideally, the system should be calibrated between patient tests and a calibration logbook should be maintained so that long-term trends can be monitored [11].

Exercise testing modalities normally involve either treadmill walking or cycle ergometry. If we compare protocol type and workload between participant sub-groups, wide variations exist. For example, in elite endurance male athletes, the British Association of Sport and Exercise Sciences [12] recommends that initial treadmill belt speed should be 15.0 km.h^–1 and should increase 1 km.h^–1 every 3 min. In elite female athletes, initial belt speed should be 13.0 km.h^–1 with the same incremental rate. Gradient should be fixed at 1%. Participants should complete between 5 to 9 stages. Using this protocol, maximal oxygen uptake values for typical elite endurance athletes range from 80-90 ml.kg^–1 min^–1 in males, and 70-80 ml.kg^–1 min^–1 in females. In healthy participants, maximal oxygen uptake varies greatly depending on individual fitness levels. For example, in 40-49 year old males, 45 ml.kg^–1 min^–1 has been classified as a "superior" level of aerobic fitness compared to 33 ml.kg^–1 min^–1 which is classified as "poor". In females of the same age, >37 ml.kg^–1 min^–1 is "superior" and 27 ml.kg^–1 min^–1 is classified as "poor". [13]

Treadmill protocols normally elicit higher peak oxygen uptake values (10%) and lead to a greater hyperventilation during exercise [10]. Cycle ergometer tests are more often stopped due to fatigue, conversely, treadmill protocols are more likely to be stopped due to breathlessness even at the same intensity of exercise [10]. This observation may be due to the rate of change of workload selection.

The modified Bruce treadmill protocol which elicits an initial treadmill belt speed of 2.7 km h^–1 (2.3 METs), may be too severe for many elderly CHF patients. We have previously reported that 40-50% cannot complete a modified Bruce protocol, defined by an inability to complete the CPET with a peak respiratory exchange ratio (pRER) >1.0 [14]. The modified Bruce protocol employs relatively large and unequal increments every 3 min and it has been recommended by the American College of Sports Medicine [9] that the modified Naughton protocol, with smaller increments may be more suitable for patients with cardiovascular disease. The modified Naughton is an incremental protocol with 2-min stages and increments in both gradient and velocity of approximately 1 MET. If one agrees that a test protocol of 10-15 min duration is optimal, then the modified Naughton may be inappropriate for patients with milder heart failure, as CPETs in these patients can far exceed 15 min. For patients with milder heart failure, a modified or full Bruce protocol may be more appropriate [15].

For cycle ergometer protocols, an increment rate of 10 W min^–1 has been recommended and is generally well tolerated in CHF patients [8]. Assessing the perception of symptom severity is normally achieved through a numerical analogue scale. Ratings of perceived exertion, often termed the Borg scale [16] is the most commonly used, and can assist with exercise prescription and adjustments in the intensity of activity.

	3. Exercise physiology

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Oxygen uptake is determined by cellular oxygen demand and can be calculated from blood flow and oxygen extraction by the tissues, as expressed by the Fick equation:

Where indicates cardiac output (mL.beat^–1), O₂ is oxygen uptake, and [C(a-) O₂] indicates the arterio-venous oxygen content difference.

Cardiac output (a linear function of O₂) increases linearly with workload to support the increasing metabolic demands of the working musculature. Indeed, during maximal exercise, 75-88% of the distribution of cardiac output is towards the active musculature in healthy controls [34]. C(a-) O₂ is related to oxygen extraction and can increase three to four-fold during maximal exercise increasing from (on average) 5 mL dL^–1 at rest to 15-20 mL dL^–1 during maximal exercise in healthy controls [35]. At lower exercise intensities, increases in are accomplished by increases in both stroke volume (SV) and heart rate (HR), whereas at moderate to higher intensities is almost exclusively increased by concomitant HR rises. The increase in is largely driven by vagal withdrawal and by increases in catecholamine response to exercise.

Individual differences in oxygen availability will relate to oxygen-carrying capacity of the blood (haemoglobin concentration), oxyhaemoglobin dissociation curve shifts in relation to changes in PO₂, PCO₂, temperature regulation, and acid-base balance), cardiac function (HR, SV), redistribution of peripheral blood flow, and oxygen extraction by the skeletal muscles (capillary density, mitochondrial density, adequacy of perfusion, and tissue diffusion) [11].

	4. Respiratory disease in CHF

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Respiratory limitations affecting exercise capacity include generation of greater inspiratory muscle pressures [17], reduced lung compliance and elevated airway resistance [18]. Respiratory muscle strength [19,20] and endurance [21] are also reduced, and changes in diaphragm position occur [22] making patients susceptible to diaphragmatic fatigue during exercise [23].

Lung disease often co-exists with CHF, so ultimately, exercise limitation may be the result of a number of different co-morbidities. A restrictive pattern of pulmonary impairment has been well-documented in CHF patients [24-27] attributed mainly to interstitial and alveolar pulmonary oedema [28]. The occurrence of restrictive lung abnormalities results in a lower rate of increase in tidal volume (V_T), higher respiratory rate (RR), and higher dead space to tidal volume ratio (V_DV_T) for a given workload. Therefore, prior to CPET, it is recommended that inspiratory capacity (IC), forced expiratory volume in 1 s (FEV₁) and forced vital capacity are assessed in each patient [29].

In order to identify pulmonary causes of exercise intolerance it is recommended that two breathing manoeuvres are completed through the metabolic cart prior to the exercise test. The first measures IC and requires the patient to achieve a steady tidal volume and end-expiratory lung volume. Patients are then instructed to fully inspire from end-expiratory lung volume to total lung capacity and then revert to normal breathing [30]. The second test is a forced manoeuvre where the variables of interest are FVC and FEV₁. To identify a pulmonary limitation it is important to assess the maximal voluntary ventilation (MVV) which is the maximum volume of air that can be breathed in and out during 1 min [31]. To perform this manoeuvre effectively is extremely difficult for patients. Therefore, we recommend that estimated MVV (eMVV) is calculated using the following formula: FEV₁^*40 [32]. The ventilatory reserve (VR) relates the ventilatory response during maximal exercise to the maximum ability to breathe. VR can be estimated as the difference between the eMVV and the peak minute ventilation (pVE) following the CPET. A VR approaching or exceeding 100% of predicted (reduced reserve) is indicative of concurrent respiratory disease and is not uncommon in CHF [33]. It is considered that patients have a pulmonary limitation if the exercise tidal volume reaches the IC, particularly early during a ramped exercise protocol, or if the breathing frequency exceeds 50 breaths per min [11]. Tidal volume does not normally exceed 70% of the IC during exercise, but increases to a value approaching 100% are seen in patients with restrictive lung disease. These relations can be identified through the nine panelled array (Wasserman-9) option available on most metablic carts after the conclusion of the CPET.

	5. Prognostic value of CPET

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Peak oxygen uptake (peak O₂) is regarded as the "gold-standard" measure of aerobic fitness. The term "O₂ max" is often referenced by physiologists and conceptually refers to a plateau in oxygen uptake in line with increasing workload. However, CHF patients are normally unable to exercise to such a level, therefore, the term peak O₂ is used. Since a low peak O₂ implies poor outcome independently from other risk factors it is often used for stratifying risk. The optimal cut-off point is often debated and while it is agreed that a peak O₂>18 mL.kg^–1 min^–1 identifies low risk patients [36], a cut-off of 14 mL.kg^–1 min^–1 is no longer viewed as appropriate for cardiac transplantation because of improved survival in patients treated with beta-blockers. Patients on beta-blockers with a peak O₂<14 mL.kg^–1 min^–1 have a better outcome than non-beta-blocked patients with a peak O₂>14 mL.kg^–1 min^–1 [37]. A contemporary cut-off of 10 mL.kg^–1 min^–1 has been used for cardiac transplant selection [36]. Females with CHF have lower peak O₂ levels than males but despite this they often have better survival rates. Elmariah and colleagues [38] suggested that gender-specific thresholds for peak oxygen uptake may be necessary for heart transplantation timing. For example, in females, a peak oxygen uptake threshold of <10 ml.kg^–1 min^–1 may be appropriate, while in males, 11.5 ml.kg^–1 min^–1 may be more suitable [38].

In healthy individuals, peak O₂ is affected by gender and age. In addition, because oxygen uptake is relativised for body mass, heavier patients with a similar fitness level will have a lower peak O₂. Therefore, when considering an individual patient for transplant, one must consider adjustments for age, gender and body mass of the patient [39]. A modification for lean body mass has also been recommended because adipose tissue is metabolically inert [40].

Assessment of peak O₂ threshold can be problematic in some CHF patients, issues including deconditioning and high body mass, lack of motivation, and difficulty exercising with a face-mask/mouthpiece in situ are issues frequently experienced by clinicians [41]. Therefore, for risk stratification purposes, peak O₂ is often considered in conjunction with other markers including the augmented ventilatory response to exercise. In recent years, some studies have shown that the VE/VCO₂ slope more powerfully predicts mortality than peak VO₂ alone [42], although the addition of peak VO₂ has an additive effect in the multivariable model [43-46].

As a result of these inherent difficulties in attaining a "true" peak oxygen uptake, researchers have looked beyond CPET variables to identify suitable transplant criteria. Other clinical parameters have been combined into validated prediction models such as the Heart Failure Survival Score (HFSS) and the Seattle Heart Failure Model (SHFM). The HFSS is derived from the mathematical manipulation of seven key clinical variables which have shown to be independently predictive of survival. Green and colleagues [47] showed that both peak oxygen uptake and the HFSS were excellent predictors of survival in females with CHF. Likewise, the SHFM uses 10 clinical variables and has been shown to provide an accurate estimate of mean, 1-, 2-, and 3-year survival rates [48]. A benefit of the SHFM is that it accounts for changes in pharmacological therapy and the additive effect of implantable devices. The addition of BNP was found to provide further predictive power at 1 year and at 5 years [49].

	6. E/CO2 slope

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
The relation between ventilation and carbon dioxide production during incremental exercise is atypical in CHF. Patients with an abnormally high E/CO₂ slope (typically >34) are at a greater risk of a cardiovascular event [50-52]. The E/CO₂ slope can be described by the following relationship:

Where, 863 is a constant (corrects for different environmental conditions, and assumes core temperature of 37 °C), V_D/V_T is the physiological dead space/tidal volume ratio, and PaCO₂ is the arterial CO₂ partial pressure.

PaCO₂ is unchanged or shows a small increase up to the respiratory compensation point but falls steadily above until test termination [53,54]. Therefore, if the VE/VCO₂ slope increases yet PaCO₂ decreases then an increase in dead space ventilation must be responsible [55]. Airways can be ventilated, but underperfused resulting in wasted ventilation or "dead space". Dead space is represented by both anatomic (fixed volume of the respiratory zone not involved in gaseous exchange), and physiologic, represented by addition of anatomical and alveolar dead space. At rest, anatomic dead space (V_D) is 150 ml in an average-sized adult and V_T is 500 ml. Consequently, V_D/V_T would be 0.3 (normal range=0.3-0.4, but is age and health dependent). During heavy exercise, conducting airway volume is 200 ml, and V_T is around 2.5 L, therefore V_D/V_T is 0.10 (200/2500) in the same adult. Higher values are seen in patients with lung disease. There is evidence, that dead space ventilation may not be the principal cause of ventilatory inefficiency in CHF. For example, dead space ventilation worsens as exercise intensity progresses; however, overbreathing is evident from the onset of exercise.

The control of breathing, specifically peripheral and central chemoreflex deregulation is affected in CHF which contributes to the abnormal ventilatory response to exercise. Similarly, augmented ergoreceptor activation (the ergoreflex) results in sympathetic activation, vasoconstriction, and hyperventilation during exercise in CHF [56]. The ergoreflex correlates with VE/VCO₂ slope and inversely with exercise tolerance in CHF.

The theory that peripheral muscle receptors (metabo- or mechanoreceptors) produce an abnormal ergoreflex resulting in an abnormal VE/VCO₂ slope during exercise has been used to explain breathlessness and fatigue in CHF [57]. Witte and Clark's [5] unifying hypothesis for ventilatory inefficiency suggests that in weak, structurally abnormal and inefficient skeletal muscle, incremental exercise produces a greater relative production of metabolic products leading to an increased ergoreflex in CHF. As a result, there is increased ventilation relative to carbon dioxide production, thus increasing the VE/VCO₂ slope and reducing PaCO₂. The interested reader is directed to Witte and Clark [5], and Tumminello and colleagues [58] for a more detailed discussion.

Pharmacological intervention can also affect the relation between VE and VCO₂, for example, carvedilol reduces the gradient of the slope, without changing V_D/V_T [59]. It is possible that β-blockers may attenuate catecholamine activation of central and peripheral chemoreceptors [60]. Interestingly, Clark and Cleland [61] have argued that β-blockers may affect metabolic activity by delaying the switch from fatty acid to carbohydrate utilization during incremental exercise by suppressing the respiratory exchange ratio (VCO₂/VO₂). Adjunctive therapies such as sildenafil inhibit the nitric oxide pathway and have been shown to reduce the VE/VCO₂ slope during exercise [62]. Continuous positive airway pressure (CPAP) used on patients with central and obstructive sleep apnoea has also been shown to reduce ventilatory inefficiency in CHF [63]. Exercise training can also improve ventilatory inefficiency by improving alveolar-capillary membrane diffusion [64], reducing exercise-induced sympathetic activity and catecholamine responses [65], and reducing metabolic markers involved in ergoreflex overactivity [66].

	7. Anaerobic threshold

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
The point at which anaerobic metabolism supplements aerobic energy requirements has been termed the anaerobic threshold (AT), and it is accompanied by a net gain in lactate production. The AT and its ventilatory exchange analogue, the lactic acidosis threshold (LAT) are critical for prognostic and diagnostic purposes in CHF. The LAT is also a surrogate measure of outcome in patients. A LAT of <11 mL.kg^–1 min^–1 and E/CO₂ slope >34 was a better indicator of risk associated with early cardiac death than O₂ peak alone in patients being prioritised for cardiac transplantation [67]. It has been recommended that the AT should be determined by the non-linear increase in the CO₂/O₂ slope (V-slope method) [68].

	8. Diagnostic potential of CPET

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
The diagnostic value of CPET is controversial and the interested reader is directed to Wasserman and colleagues' seminal works [11]. In CHF, metabolic responses to exercise are abnormal and manifest in the following ways:

Peak work rate, AT and peak O₂ are lower compared to age-matched healthy controls reflecting impaired exercise tolerance in CHF. Increased breathing frequency and V_T are often seen. Early exercise cessation and reduced peak O₂ are associated with a reduced peak VE and a large ventilatory reserve. The VO₂/WR relationship is decreased above the AT (<10) [69] (Table 1).

View this table: [in this window] [in a new window]   Table 1 Routinely collected cardiopulmonary exercise test variables

 
Predicted peak heart rate [220 beats.min^–1–age (years)] is reduced due to beta-blockade, early fatigue, or chronotopic incompetence. Little or no heart rate reserve is evident in mild or more severe CHF. Increased heart rate response relative to oxygen uptake is observed. The relation between HR and O₂ is termed the "oxygen pulse" and reflects the amount of oxygen extracted per beat. Oxygen pulse has often been used as an estimator for SV although this is controversial in patients who desaturate. The oxygen pulse increases linearly with incremental exercise in healthy controls. At maximal or near maximal exercise the slope flattens as it is assumed that the arterio-venous mixed oxygen difference is maximal [8]. A low, unchanging or shallow oxygen pulse suggests poor oxygen extraction of the skeletal muscles and is seen in patients who may be deconditioned or suffer from cardiovascular disease. The peak oxygen pulse and estimated peak stroke volume [(O₂ pulse/haemoglobin concentration)^*100] is reduced in CHF [70]. In some patients, an immediate post-exercise increase in O₂ pulse is evident probably caused by an abrupt decrease in left ventricular afterload when exercise ends [71]. Early metabolic acidosis often develops because cannot increase to a proportionate level with increasing workload [72,73]. (Table 2).

View this table: [in this window] [in a new window]   Table 2 CPET responses in patients with CHF

 

	9. Exercise oscillatory ventilation

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
Exercise oscillatory ventilation (EOV) or periodic breathing manifests as a cyclic breathing pattern that promotes oscillations in minute ventilation during incremental exercise, especially at lower exercise intensities in CHF patients. Prevalence of EOV is difficult to determine, mainly due to the lack of standardisation of criteria for determining EOV [74,75]. In published investigations, prevalence ranges from 12 to 35% [74-78].

EOV at rest does not hold the same prognostic significance as during physical activity. However, during exercise, EOV may be a more powerful prognosticator than VE/VCO₂ slope [77]. A recent study [79] has shown that EOV is possibly an independent predictor of sudden cardiac death (SCD), indeed, of 33 deaths due to SCD, each patient had a diagnosis of EOV. The authors also concluded that prevalence of EOV may be useful for screening suitability for ICD therapy. EOV often co-exists with central sleep apnoea. The relation between sleep disordered breathing and EOV is an interesting one. A study by Corra and colleagues [75] showed that EOV is significantly associated with an apnoea/hypopnoea index >30/h and concluded that while each breathing disorder alone is linked to survival, their combination has a more profound prognostic millstone.

EOV is associated with a more advanced clinical status, cardiac impairment, and reduced exercise capacity, and may reflect a more severe derangement of the ventilatory control system [76]. The ventilatory hypothesis is based on an abnormal chemoreceptor feedback which leads to a ventilatory control flux resulting in the typical "saw-toothed" breathing pattern. Oscillatory flow through the pulmonary circulation may also cause changes to arterial blood gases and pH. A circulatory delay has been reported in CHF patients that could induce a loss of synchronisation between the lung and the ventilatory control system [58].

	10. Conclusions

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
The non-invasive value of CPET for risk stratification and transplant selection is commonly acknowledged. It can also be used for distinguishing between cardiac and pulmonary causes of exercise intolerance, however, its diagnostic potential is less widely documented in CHF patients. To improve our understanding and confidence, clinicians must develop reference values and ranges for CHF patients from a co-ordinated multicentre approach. This will require a standardisation of equipment, and protocols as well as data interpretation. Consequently, this must be driven by appropriate governing bodies e.g. ESC. There is also a need to establish CPET criteria for establishing the severity of dysfunction. Currently, because the diagnostic value of CPET is not internationally accepted in CHF, data should only be used for confirmatory analysis in conjunction with further investigation. For medical centres considering CPET as an adjunct to current service provision, initial start-up costs will be relatively high. In addition, staff training will be required, and there will be modest ongoing consumable and service costs. However, costs incurred are modest when compared to other tests routinely used by cardiologists, and in addition, CPET is safe for cardiac patients with few events reported. The use of CPET technology is becoming increasingly prevalent in cardiology services, and it is likely that, in the future, CPET will take a more prominent role in guiding patient management provision.

	Notes

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 
^* Tel.: +44 113 8123246. E-mail address: L.Ingle{at}leedsmet.ac.uk

	References

Top Notes Abstract 1. Introduction 2. Practical considerations of... 3. Exercise physiology 4. Respiratory disease in... 5. Prognostic value of... 6. VE/VCO2 slope 7. Anaerobic threshold 8. Diagnostic potential of... 9. Exercise oscillatory... 10. Conclusions References

 

1. Nieminen M.S., Bohm M., Cowie M.R., et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J (2005) 26(4):384–416.[Free Full Text]
2. Sullivan M.J., Higginbotham M.B., Cobb F.R. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite haemodynamic and pulmonary abnormalities. Circulation (1988) 77:552–559.[Abstract/Free Full Text]
3. Williams A.D., Selig S., Hare D.L., et al. Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity. J Cardiac Fail (2004) 10:141–148.[CrossRef][Web of Science][Medline]
4. Sullivan M.J., Green H.J., Cobb F.R. Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. Circulation (1990) 81:518–527.[Abstract/Free Full Text]
5. Witte K.K., Clark A.L. Why does chronic heart failure cause breathlessness and fatigue? Prog Cardiovasc Dis (2007) 49(5):366–384.[CrossRef][Web of Science][Medline]
6. Ingle L., Rigby A.S., Carroll S., et al. Prognostic value of the 6-min walk test and symptom severity in older patients with left ventricular systolic dysfunction. Eur Heart J (2007) 28(5):560–608.[Abstract/Free Full Text]
7. Ingle L., Shelton R.J., Rigby A.S., et al. The reproducibility and sensitivity of the 6-minute walk test in elderly patients with chronic heart failure. Euro Heart J (2005) 26:1742–1751.[Abstract/Free Full Text]
8. ESC Working Group on Exercise Physiology. Physiopathology and electrocardiography. Guidelines for cardiac exercise testing. Euro Heart J (1993) 14:969–988.[Free Full Text]
9. American College of Sports Medicine (ACSM) Guidelines for Exercise Testing and Prescription. (2000) 6th Edition. London: Williams and Wilkins.
10. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation (2002) 106(14):1883–1892.[Free Full Text] Witte K.K., Clark A.L. Cycle exercise causes a lower ventilatory response to exercise in chronic heart failure. Heart (2005) 91(2):225–226.[Free Full Text]
11. Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp B. Principles of Exercise Testing and Interpretation. (2005) Fourth Edition. London: Lippincott, Williams and Wilkins.
12. British Association of Sports and Exercise Sciences. Sport and exercise physiology guidelines. In: Volume One — Sport Testing—Winter E.M., Jones A.M., Davison R.R.C., Bromley P.D., Mercer T.H., eds. (2007) London: Routledge. 147–154.
13. Heyward V. Advanced fitness assessment and exercise prescription. (1998) Champaign, Il: Human Kinetics. 47–81.
14. Ingle L., Carroll S. The 6-min walk test: a useful test in elderly patients with heart failure? Med Sci Sports Ex (2007) 39(2):391.[CrossRef]
15. Kleber F.X., Waurick P., Winterhalter M. CPET in heart failure. Eur Heart J Suppl (2004) 6(Supplement_D):D1–D4.[Abstract/Free Full Text]
16. Borg G. Subjective effort and physical activities. Scand J Rehabil (1978) 6:108–113.
17. McParland C., Krishnan B., Wang Y., et al. Inspiratory muscle weakness and dyspnea in chronic heart failure. Am Rev Respir Dis (1992) 146:467–472.[Web of Science][Medline]
18. Witte K.K.A., Morice A., Clark A.L., et al. Airway resistance in chronic heart failure measured by impulse oscillometry. J Cardiac Fail (2002) 8:225–231.[CrossRef][Web of Science][Medline]
19. Evans S.A., Watson L., Hawkins M., et al. Respiratory muscle strength in chronic heart failure. Thorax (1995) 50:625–628.[Abstract/Free Full Text]
20. Hammond M.D., Bauer K.A., Sharp J.T., Rocha D. Respiratory muscle strength in congestive heart failure. Chest (1990) 98:1091–1094.[Abstract/Free Full Text]
21. Mancini D.M., Henson D., LaManca J., Levine S. Evidence of reduced respiratory muscle endurance in patients with heart failure. J Am Coll Cardiol (1994) 24:972–981.[Abstract]
22. Caruana L., Petrie M.C., McMurray J.J., et al. Altered diaphragm position and function in patients with chronic heart failure. Euro J Heart Fail (2001) 3:183–187.[CrossRef]
23. Kufel T.J., Pineda L.A., Junega R.G., Hathwar R., Mador M.J. Diaphragmatic function after intense exercise in congestive heart failure patients. Eur Respir J (2002) 20:1399–1405.[Abstract/Free Full Text]
24. Guazzi M., Agostoni P., Matturri M., et al. Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol. Am Heart J (1999) 138:460–467.[CrossRef][Web of Science][Medline]
25. Ravenscraft S.A., Gross C.R., Kubo S.H., et al. Pulmonary function after successful heart transplantation. Chest (1993) 103:54–58.[Medline]
26. Faggiano P., Lombardi C., Sorgato A., et al. Pulmonary function tests in patients with congestive heart failure: effects of medical therapy. Cardiology (1993) 83:30–35.[CrossRef][Web of Science][Medline]
27. Puri S., Dutka D.P., Baker L., et al. Acute saline infusion reduces alveolar-capillary membrane conductance and increases airflow obstruction in patients with left ventricular dysfunction. Circulation (1999) 99:1190–1196.[Abstract/Free Full Text]
28. Hauge A., Bo G., Waaler B.A. Interrelations between pulmonary liquid volumes and lung compliance. J Appl Physiol (1975) 38:608–614.[Abstract/Free Full Text]
29. Ingle L. Theoretical rationale and practical recommendations for cardiopulmonary exercise testing in patients with chronic heart failure. Heart Fail Rev (2007) 12(1):12–22.[CrossRef][Web of Science][Medline]
30. Marin J.M., Carrizo S.J., Gascon M., et al. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med (2001) 163:1395–1399.[Abstract/Free Full Text]
31. Faggiano P., Lombardi C., Sorgato A., et al. Pulmonary function tests in patients with congestive heart failure: effects of medical therapy. Cardiology (1993) 83:30–35.[CrossRef][Web of Science][Medline]
32. Campbell S.C. A comparison of the maximal volume ventilation with forced expiratory volume in one second: an assessment of subject cooperation. J Occup Med (1982) 24:531–533.[Web of Science][Medline]
33. Weisman I.M., Zeballos R.J. Integrative approach to the interpretation of cardiopulmonary exercise testing. Weisman I.M., Zeballos R.J., Gore C.J., et al, eds. (2002) Basel, Switzerland: Karger. 300–322.
34. Anderson K.L. The cardiovascular system in exercise. In: Exercise Physiology—Falls H.B., ed. (1968) New York: Academic Press.
35. Saltin B. Physiological effects of physical conditioning. Medicine and Science in Sports (1969) 1(1):50–56.
36. Fleg J.L., Pina I.L., Balady G.J., et al. Assessment of functional capacity in clinical and research applications: an advisory from the Committee on Exercise, Rehabilitation and Prevention, Council on Clinical Cardiology, American Heart Association. Circulation (2000) 102:1591–1597.[Free Full Text]
37. Zugck C., Haunstetter A., Kruger C., et al. Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure. J Am Coll Cardiol (2002) 39:1615–1622.[Abstract/Free Full Text]
38. Elmariah S., Goldberg L.R., Allen M.T., Kao A. Effects of gender on peak oxygen consumption and the timing of cardiac transplantation. J Am Coll Cardiol (2006) 47(11):2237–2242.[Abstract/Free Full Text]
39. Working Group on Cardiac Rehabilitation and Exercise Physiology and Working Group on Heart Failure for the European Society of Cardiology. Recommendations for exercise testing in chronic heart failure patients. Eur Heart J (2001) 22:37–45.[Free Full Text]
40. Cicoira M., Davos C.H., Francis D.P., et al. Prediction of mortality in chronic heart failure from peak oxygen consumption adjusted for either body weight or lean tissue. J Cardiac Failure (2004) 10:421–426.[CrossRef][Web of Science][Medline]
41. Mehra M.R., Kobashigawa J., Starling R., et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J Heart Lung Transplant (2006) 25(9):1024–1042.[CrossRef][Web of Science][Medline]
42. Arena R., Myers J., Abella J., et al. Development of a ventilatory classification system in patients with heart failure. Circulation (2007) 115:2410–2417.[Abstract/Free Full Text]
43. Corra U., Mezzani A., Bosimini E., et al. Limited predictive value of cardiopulmonary exercise indices in patients with moderate chronic heart failure treated with carvedilol. Am Heart J (2004) 147:553–560.[CrossRef][Web of Science][Medline]
44. Arena R., Myers J., Abella J., Peberdy M.A. Influence of heart failure etiology on the prognostic value of peak oxygen consumption and minute ventilation/carbon dioxide production slope. Chest (2005) 128:2812–2817.[Abstract/Free Full Text]
45. Guazzi M., Arena R., Myers J. Comparison of the prognostic value of cardiopulmonary exercise testing between male and female patients with heart failure. Int J Cardiol (2006) 113:395–400.[CrossRef][Web of Science][Medline]
46. Bard R.L., Gillespie B.W., Clarke N.S., Egan T.G., Nicklas J.M. Determining the best ventilatory efficiency measure to predict mortality in patients with heart failure. J Heart Lung Transplant (2006) 25:589–595.[CrossRef][Web of Science][Medline]
47. Green P., Lund L.H., Mancini D. Comparison of peak exercise oxygen consumption and the heart failure survival score for predicting prognosis in women versus men. Am J Cardiol (2007) 99:399–403.[CrossRef][Web of Science][Medline]
48. Levy W.C., Mozaffarian D., Linker D.T., et al. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation (2006) 113:1424–1433.[Abstract/Free Full Text]
49. May H.T., Horne B.D., Levy W.C., et al. Validation of the seattle heart failure model in a community-based heart failure population and enhancement by adding B-type natriuretic peptide. Am J Cardiol (2007) 100:697–700.[CrossRef][Web of Science][Medline]
50. Arena R., Myers J., Abella J., et al. Development of a ventilatory classification system in patients with heart failure. Circulation (2007) 115(18):2410–2417.[Abstract/Free Full Text]
51. Nanas S.N., Nanas J.N., Sakellariou D.C., et al. VE/VCO₂ slope is associated with abnormal resting haemodynamics and is a predictor of long-term survival in chronic heart failure. Eur J Heart Fail (2006) 8(4):420–427.[Abstract/Free Full Text]
52. Tabet J.Y., Beauvais F., Thabut G., et al. A critical appraisal of the prognostic value of the VE/VCO₂ slope in chronic heart failure. Eur J Cardiovasc Prev Rehabil (2003) 10(4):267–272.[CrossRef][Web of Science][Medline]
53. Rubin S.A., Brown H.V., Swan H.J.C. Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment. Circulation (1982) 66:143–148.[Abstract/Free Full Text]
54. Clark A.L., Coats A.J.S. Usefulness of arterial blood gas estimations during exercise in patients with chronic heart failure. Br Heart J (1994) 71:528–530.[Abstract/Free Full Text]
55. Sullivan M.J., Higginbotham M.B., Cobb F.R. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodyamic and pulmonary abnormalities. Circulation (1988) 77:552–559.[Abstract/Free Full Text]
56. Piepoli M., Clark A.M., Volterrani M., et al. Contribution of muscle afferents to the hemodynamic, autonomic, ventilatory responses to exercise in patients with chronic heart failure. Circulation (1996) 93:940–952.[Abstract/Free Full Text]
57. Clark A.L., Poole-Wilson P.A., Coats A.J., et al. Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol (1996) 28:1092–1102.[Abstract]
58. Tumminello G., Guazzi M., Lancellotti P., et al. Exercise ventilation inefficiency in heart failure: pathophysiological and clinical significance. Euro Heart J (2007) 28:673–678.[Abstract/Free Full Text]
59. Agostoni P.G., Guazzi M., Bussotti M., et al. Carvedilol reduces the inappropriate increase of ventilation during exercise in heart failure patients. Chest (2002) 122:2062–2067.[Abstract/Free Full Text]
60. Butland R.J., Pang J.A., Geddes D.M. The selectivity of the beta-adrenoceptor for ventilation in man. Br J Clin Pharmacol (1982) 14:707–711.[Web of Science][Medline]
61. Clark A.L., Cleland J.G.F. Beta-blockers exercise ventilation in chronic heart failure. J Card Failure (2005) 5:340–342.
62. Guazzi M., Tumminello G., DiMarco F., et al. The effect of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilation efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol (2004) 44:2339–2348.[Abstract/Free Full Text]
63. Arzt M., Schulz M., Wensel R., et al. Nocturnal positive airway pressure improves ventilatory efficiency during exercise in patients with chronic heart failure. Chest (2005) 127:794–802.[Abstract/Free Full Text]
64. Guazzi M., Reina G., Tumminello G., et al. Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure. J Appl Physiol (2004) 97:1866–1873.[Abstract/Free Full Text]
65. Belardinelli R., Georgiou D., Purcaro A. Low dose dobutamine echocardiography predicts improvement in functional capacity after exercise training in patients with ischaemic cardiomyopathy: prognostic implication. J Am Coll Cardiol (1998) 31:1027–1034.[Abstract/Free Full Text]
66. Adamopoulos S., Coats A.J., Brunotte F., et al. Physical training improves skeletal muscle metabolic abnormalities in patients with chronic heart failure. J Am Coll Cardiol (1993) 23:1101–1106.
67. Gitt A.K., Wasserman K., Kilkowski C., et al. Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation (2002) 106:3079–3084.[Abstract/Free Full Text]
68. Beaver W.L., Wasserman K., Whipp B.J. A new method for detecting the anaerobic threshold by gas exchange. J Appl Physiol (1986) 60:2020–2027.[Abstract/Free Full Text]
69. Hansen J.E., Casaburi R., Cooper D.M., et al. Oxygen uptake as related to work rate increment during cycle ergometer exercise. Eur J Appl Physiol (1988) 57:140–145.[CrossRef][Web of Science]
70. Belardinelli R., Lacalaprice F., Carle F., et al. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing. Eur Heart J (2003) 24(14):1304–1313.[Abstract/Free Full Text]
71. Koike A., Itoh H., Doi M., et al. Beat-to-beat evaluation of cardiac function during recovery from upright bicycle exercise in patients with coronary artery disease. Am Heart J (1990) 120:316–323.[CrossRef][Web of Science][Medline]
72. Sullivan M.J., Cobb F.R. Relation between central and peripheral haemodynamics during exercise in patients with chronic heart failure. Circulation (1989) 80:769–781.[Abstract/Free Full Text]
73. Wilson J.R., Martin J.L., Schwartz D., et al. Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation (1984) 69:1079–1087.[Abstract/Free Full Text]
74. Leite J.J., Mansur A.J., de Freitas H.F., et al. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol (2003) 41:2175–2181.[Abstract/Free Full Text]
75. Corrà U., Pistono M., Mezzani A., et al. Sleep and exertional periodic breathing in chronic heart failure — prognostic importance and interdependence. Circulation. (2006) 113:44–50.[Abstract/Free Full Text]
76. Corra U., Giordano A., Bosimini E., et al. Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications. Chest (2002) 21(5):1572–1580.
77. Guazzi M., Arena R., Ascione A., Piepoli M., Guazzi M.D. Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value. American Heart Journal (2007) 153:859–867.[CrossRef][Web of Science][Medline]
78. Francis D.P., Davies L.C., Willson K., et al. Impact of periodic breathing on measurement of oxygen uptake and respiratory exchange ratio during cardiopulmonary exercise testing. Clinical Science (2002) 103:543–552.[Web of Science][Medline]
79. Guazzi M., Raimondo R., Vicenzi M., et al. J Am Coll Cardiol (2007) 50:299–308.[Abstract/Free Full Text]
80. ATS/ACCP Statement on Cardiopulmonary Exercise Testing. Joint Statement of the American Thoracic Society ( ATS ) and the American College of Chest Physicians (ACCP). Am J Respir Crit Care Med (2003) 167:211–277.[Free Full Text]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				H. Ukkonen, I. G. Burwash, W. Dafoe, R. A. de Kemp, H. Haddad, K. Yoshinaga, R. A. Davies, E. K. Gannon, J. N. DaSilva, and R. S.B. Beanlands Is ventilatory efficiency (VE/VCO2 slope) associated with right ventricular oxidative metabolism in patients with congestive heart failure? Eur J Heart Fail, November 1, 2008; 10(11): 1117 - 1122. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (3) Request Permissions Disclaimer Google Scholar Articles by Ingle, L. Search for Related Content PubMed PubMed Citation Articles by Ingle, L. Social Bookmarking          What's this?

Online ISSN 1879-0844 - Print ISSN 1388-9842

Copyright © 2010 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics