eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
2/2005
vol. 1
 
Share:
Share:
more
 
 

Review paper
A reappraisal of concepts in heart failure: Central role of cardiac power reserve

Simon G. Williams
,
Diane Barker
,
David F. Goldspink
,
Lip-Bun Tan

Arch Med Sci 2005; 1, 2: 65-74
Online publish date: 2005/09/21
Article file
- A reappraisal.pdf  [0.12 MB]
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 
Submitted: 12 June 2005
Accepted: 5 July 2005



Corresponding author:
Lip-Bun Tan, DPhil, FRCP, FESC
Consultant Cardiologist
Leeds General Infirmary
Leeds, LS1 3EX, UK
Phone: +44 (0)113 392 5401
Fax: +44 (0)113 392 5395





Introduction
Some misleading concepts of heart failure
There are some conceptual cul-de-sacs that have been rather influential in the field of heart failure. The first one is the reliance by clinicians on measurements made with the patients comfortably resting using sophisticated imaging techniques. A fundamental flaw in this approach is the confusion between structure and function, as exemplified by the widespread use of left ventricular ejection fraction (LVEF) in clinical practice as an indicator of cardiac "function". The second pertains to the fundamental misconception that heart failure is a problem of myocardial contractility, which needs to be "extracted" and be independent of the loading conditions affecting the myocardial contraction. The third is the belief that heart failure is exemplified by its inability to meet "the needs of the body" [5] or "to pump blood at a rate commensurate with the requirements of the metabolizing tissues" [6]. The fourth is the belief that measurements made at rest are sufficient to define the overall state of heart failure.

Imaging and LVEF
Echocardiographic representation of LVEF is perhaps the most widely used indicator of cardiac function. Although entrenched in cardiological practice and widely employed as an inclusion requirement into clinical trials, it is not a panacea. It is usually measured at rest. It has previously been shown to correlate well with mortality [7-9], but does not correlate with functional capacity as measured by exercise duration, METS achieved or peak VO2 [10-14]. When the heart begins to fail, a key manifestation is exercise intolerance. For a measurement purported to represent cardiac function to show very poor correlation with exercise capacity, questions should be asked whether such a measure is truly a reliable representation of HF.
LVEF is equal to stroke volume (SV) divided by the LV end-diastolic volume (LVEDV), LVEF=SV/LVEDV. End-diastolic dimensions or volume are essentially an indication of the structure of the LV, just as a necessary part of the description of the structure of a container is given by describing its dimensions. Therefore, in this equation, only the numerator is possibly an indication of cardiac function. However, it is also known that compensatory mechanisms are triggered following an insult to the heart in an attempt to maintain the SV as constant as possible. In other words, the decrease in LVEF following cardiac impairment is largely a relative constant divided by the enlarging LVEDV. Thus, LVEF can be viewed as the reciprocal of LVEDV, and therefore an indicator of structure. This is probably why LVEF correlates poorly with exercise capacity or cardiac function [15].
The operative concept in HF is impairment of function, of instead structure which may or may not have contributed to the dysfunction. It is therefore vitally important, when viewing images of the heart, to distinguish information pertaining to function versus to structure, and the relation between the two. A commonly used term in modern HF literature is 'remodelling', which is often assumed to connote adverse remodelling (meaning ventricular chamber dilatation), although the dilatation itself may actually be physiological and compensatory [16]. To assume that all remodelling (dilatation) is adverse and should be prevented or reversed is rather simplistic. A deeper understanding of the mechanistic processes involved is necessary to avoid confusion [1].

Contractility
In the 1960s, a notion emerged that became a prevailing concept that the crucial difference between a failing and a normal heart is that the former has compromised myocardial contractility [17-19]. This led to the hunt for an "index of contractility" that was totally independent of ventricular loading conditions, especially preload and afterload [18-20]. A major objective of therapy thus became primarily to increase myocardial contractility to reverse HF. This led to a systematic development of positive inotropic agents and the emergence and testing of milrinone, enoximone, xamoterol, flosequinan, vesnarinone, and more recently levosimendan [21, 22]. However, meta-analyses of data from clinical trials of inotropic agents point to worryingly high mortality rates [23-25]. Paradoxically, powerful negative inotropic agents such as β-adrenoceptor blockers have been shown in clinical trials to produce the opposite effect of lower mortality rates [26, 27], and not all of these were due to reduction in sudden cardiac deaths [28].
With hindsight, it has become evident that the concept of increasing myocardial "indices of contractility" is flawed. After a major injury to the left ventricle, such as after a sizeable myocardial infarction or acute myocarditis, the remaining viable myocardium becomes vital in maintaining the cardiac function and provides an adequate circulation. Stimulating these remaining viable myocardium to enhance cardiac pumping by neurohormonal, pharmacological or other means would improve the indices of "contractility" (e.g. LV dp/dtmax, Vmax, Emax), but also hasten the demise of these vital cardiomyocytes, leading to vicious downward spiral of progressive LV dysfunction [1]. Rather than stressing the cardiomyocytes, the objective should be to improve impaired ventricular mechanics, such as in the presence of dyssynchrous contraction that can be corrected by cardiac resynchronisation therapy, thereby possibly sparing the need for the viable myocytes to hypercontract leading to prolonged survival [3].

Failure to meet the needs of body tissues
The concept that heart failure is exemplified by its inability to meet "the needs of the body" [5] or "the requirements of the metabolizing tissues" [6] has been so deep-seated as to be sanctioned in many formulations of definitions of heart failure [4]. Of all the nutrient needs of the body, because of the lack of any storage capacity in the tissues, the one that is most dependent on the continuous delivery via the blood propelled by the pumping action of the heart is oxygen, not glucose, free fatty acids or other ingredients of biochemical fuel. This is so crucial that apart from the heart, the only other organ in the body that receives the entire cardiac output is the lungs, in order to acquire oxygen. However, such a concept of not meeting tissue needs was debunked over two decades ago by Harris [29] who pointed out that "neither the consumption of oxygen by the body is reduced in cardiac failure" nor is there any tissue sensor that detects tissue hypo-oxygenation or hypo-metabolism and thereby triggers compensatory mechanisms [30]. Instead, he expounded that the body naturally detects the insufficiency in cardiac pumping output via the arterial baroreceptors that secondarily trigger a whole series of compensatory mechanisms in an attempt to prop up the arterial pressure. At length, he explained that nature does not cater for the heart failure condition, and in effect, these detection and compensatory systems triggered by heart failure are erroneous because they were designed not to cope with heart failure but for other purposes such as haemorrhagic shock or exercise. Subsequent clinical counteraction of these effects through pharmacotherapy (using diuretics, ACE inhibitors, β-adrenergic, angiotensin and aldosterone receptor blockers, etc) has proven to be beneficial to the patients [1, 2, 26-28, 31]. These therapies are nevertheless dealing with the secondary effects of heart failure. Dealing with the primary defect of cardiac pump dysfunction is even more fundamental, but the present clinical predicament is whether there is a reliable way of measuring the primary functional inadequacy of cardiac pumping, that also takes into account the natural detection system already in place through evolution [29].

Measurements made at rest
are unrepresentative of cardiac reserve

It is axiomatic that patients with HF are more troubled by symptoms during exertion than at rest, mainly because the reserve function of the heart becomes exposed as being limited during exertion [32]. More than a century ago, Sir William Osler [33] wrote "that in these hearts, the reserve force is lost, and with it the power of meeting the demands in maintaining the circulation during severe exertion" [34]. This was probably one of the earliest recognitions by a physician (without the benefit of measuring cardiac function in vivo) that the prime cause of heart failure is the loss of cardiac reserve, and implied that its evaluation should include means of revealing such limitations through some form of maximal stress, such as severe exertion or maximal exercise testing. Conceptually, HF is primarily the failure of the cardiac pump to function adequately to support the more dynamic circulation required during exercise [15]. Conversely, the extent of impairment in pump function is indirectly represented by the diminution in exercise capacity, best measured by peak exercise oxygen consumption (VO2), but approximated by exercise duration [15]. However, in the event that the exercise diminution is likely to be caused by non-cardiac factors as well, direct evaluation of how much cardiac function is impaired will be required. In this case, the choice of variable to represent cardiac function requires careful consideration, as such a variable will need to be reliably indicative of cardiac impairment.

Cardiac functional reserve
What is clear from the above is that when measured at rest, unless the heart is in extremis and the patient is symptomatic with minimal or no exertion, it will not be able to predict how much reserve function the failing heart still possesses. The most reliable estimate of the reserve is necessarily measured at peak stimulation of the heart, during "severe exertion", as stipulated by Osler in 1895 [33].

Peak oxygen consumption
HF is a disease of exercise; exercise limitation is its principal symptom and the degree of exercise limitation is its principal prognostic indicator [32]. The addition of respiratory gas analysis to standard exercise testing has become increasingly important over the years, especially in the assessment of HF. There is a steady growth in recent years of patients awaiting transplantation relative to the availability of donor hearts. The use of peak oxygen consumption (VO2) in prognostic assessment and monitoring of this condition has become, and continues to be, standard practice [35, 36].
Exercise capacity (Figure 1), expressed as exercise duration or workload achieved has been recognised for several decades as an important prognostic marker in cardiac disease [37]. Myers and colleagues [38] showed peak exercise capacity to be the strongest predictor of all cause mortality amongst both normal subjects and those with cardiovascular disease. Exercise capacity outperformed other traditional markers of cardiovascular risk, including smoking, hypertension, diabetes, previous history of myocardial infarction or HF and hyperlipidaemia. This study concluded that, in terms of reducing mortality from any cause, improving exercise tolerance warranted at least as much attention from physicians as other major risk factors. Exercise capacity itself is a key item of the quality of life of patients with HF, which can be perceived by the patients and verified through formal exercise testing. Improving it is a major objective of therapeutic trials.
Peak VO2 (Figure 1) is a more reliable index of exercise capacity than exercise duration or workload as it represents a more precise, reproducible and physiological measure of cardiopulmonary function [32, 35]. Numerous studies published in the last decade demonstrate peak VO2 to be an independent predictor of mortality. Several small studies were published in the mid 1980's showing peak VO2, along with other factors, to be important in risk stratification in patients with HF [39-41]. Studies followed in the 1990's all indicating peak VO2 to be an independent predictor of mortality using a multivariate analysis [13, 42-48].
Some of these studies highlighted that a single cut off point for peak VO2 provided a clinically meaningful separation between patients with a high or low likelihood of survival. The study by Szlachcic and colleagues [39] was the first to suggest that a cut-off point of peak VO2 (in this case, 10 mls/kg/min) played an important role in risk stratification. More recently, a peak VO2 of
14 mls/kg/min has been used and is commonly applied in the context of selecting patients for transplantation [49]; it appears that for patients who achieve values greater than 14 mls/kg/min, the 1-year survival is similar to those who receive a transplant. This value is currently recommended as a relative indication for accepting patients for transplantation in the American Heart Association Scientific Statement on Transplantation [50]. Peak VO2 also correlates well with quality of life and symptoms [51, 52] and hospitalisation rates [53].

Limitations of peak oxygen consumption
However, peak VO2 has several key limitations in the assessment of cardiac disease. It is influenced by non-cardiac factors (Figure 1) such as muscle deconditioning, motivation for performing exercise and obesity [52, 54]. The expected peak VO2 varies according to the age and sex of the subject [55, 56] and evaluation using a percentage of the predicted peak VO2 has been suggested to be more predictive of mortality than peak VO2 alone [57]. Also, no statistical difference in survival between patients with peak VO2 levels of 10-14 mls/min/kg and those with levels of 14-18 mls/min/kg has previously been shown in some studies [39,43,49]. A large study consisting of 664 patients during a 10 year period of follow-up was carried out by Myers and colleagues [58]. A multivariate analysis revealed peak VO2 to be an independent predictor of mortality above and below a range of 10-17 mls/min/kg, rather than at a cut-off point of 14 mls/kg/ml. The non-predictive value of peak VO2 may be linked to the fact that it is only an indirect indicator of peak exercise cardiac output [39, 59, 60] and cardiac functional reserve [15]. This has led investigators to look beyond peak VO2 at other cardiopulmonary exercise derived data in the assessment of cardiac function.
Haemodynamic assessment of cardiac function
Parameters such as the blood pressure response to exercise [61-65], the ratio of minute ventilation to carbon dioxide production (VE/VCO2) [66-69] and oxygen recovery post exercise [70] have emerged in recent years as independent predictors of outcome. However, these variables are only indirectly related to cardiac function, and therefore can only be considered as markers of severity of organ failure, with direct means to improve these values not necessarily indicating an improvement in cardiac function. More direct measurements of cardiac work, represented by peak stroke work index [71, 72], cardiac output (CO) response to exercise [73] or cardiac power output, CPO [74, 75], have emerged as powerful independent predictors of prognosis over peak VO2.

Cardiac pumping capacity and cardiac reserve
The heart is a mechanical pump; its performance ranges from zero to a finite maximum. Two important terms can be applied to cardiac performance: (a) cardiac pumping capability – the maximum performance that can be achieved during stimulation, and (b) cardiac pumping reserve – the difference in performance between resting and maximally stimulated states. This concept was initially proposed by Barringer [76] in 1917 and has since been re-evaluated and modified by subsequent investigators [77-80].
Each heart has its own ceiling peak pumping performance, above which it is physically impossible to exceed (Figure 2). This value would alter only if the intrinsic condition of the heart is altered, e.g. after an acute myocardial infarction or after successful relevant cardiac surgery. When compared, these maxima of individual cardiac function are direct and objective indicators of how relatively good or impaired the hearts are as fluid pumps. They provide a means of grading the degree of functional impairment in heart failure along the scales below the norm (Figure 3), and conversely, the degree of superiority in the function of athletic hearts [79, 80].
The performance of the cardiac pump, if considered in the context of its function, can be defined by paraphrasing William Harvey's original concept as "the maintenance of the circulation to transport nutrients to meet the metabolic demands of body tissues" [81]. The delivery of oxygen to an organ depends on the rate of blood flow into the vascular bed of that organ. Thus, the first determinant of the demand imposed on the heart is the production of an adequate cardiac output (CO). One way of increasing blood flow to any tissue is by reducing its vascular resistance. Once maximum vasodilatation is achieved, the only way to increase blood flow into the tissue is by increasing arterial perfusion pressure. This increase in pressure assumes an even greater importance in the perfusion of exercising skeletal muscle because of the higher tissue pressure developed during muscle contraction, in particular during isometric exercise. Hence, the second demand imposed on the heart is the maintenance of an adequate arterial pressure. The product of cardiac output and arterial pressure is defined as cardiac power output (CPO). This term represents the overall function, equivalent to the rate of hydraulic energy imparted by the cardiac pump into the circulation to facilitate the perfusion of various metabolising tissues. By virtue of containing the arterial pressure term, CPO measurement, especially at maximal exercise, may well represent the best way of detecting and monitoring primary cardiac pump inadequacy in heart failure patients, complementing the natural detection of inadequate BP levels already afforded through evolution [29].
Cardiac pumping capability can thus be defined as the power output achieved by the heart during maximal stimulation, and cardiac pumping reserve as the increase in power output as the heart's performance is increased from resting to the maximally stimulated state. Figure 3 illustrates cardiac functional reserve of individual hearts in a normal functional state, in various degrees of HF and in cardiogenic shock.

Clinical application of cardiac work
and cardiac power output

CPO has been used by several investigators in the evaluation of cardiac disease. It is calculated as the product of the mean arterial pressure (MAP) and the cardiac output multiplied by a correction factor (2.22 X 10-3) and is expressed in watts. Maximal CPO was shown by Tan [78] in 1986 to be an accurate predictor of prognosis in a group of ambulatory patients with New York Heart Association (NYHA) functional class III-IV of heart failure. Sixty three patients with a mean LVEF of 24.2% were studied. Several invasive haemodynamic measurements were recorded at rest: Cardiac index (CI) = CO/body surface area in l/min/m2, pulmonary artery wedge pressure (PAWP), left ventricular stroke work index (LVSWI) = MAP x PAWP/HR x 0.133 J.m-2). Dobutamine was then infused as a stress agent increasing in increments of 5mcg/kg/min to a maximum of 40 mcg/kg/min.
The hypothesis tested was that a maximal CPO of <1 watt via pharmacological stimulation (assumed to be normal resting value for an average sized man) could discriminate between survivors and non-survivors at one year follow up. Of the 23 patients with a maximal CPO <1 watt, 19 died of progressive heart failure. Four patients died in the group of 40 with a maximal CPO of >1 watt. No pattern was seen with any resting parameter. Conclusions were drawn therefore that a maximal CPO of <1 watt was indicative of a poor 1-year survival, although no statistical comparison was made with the other haemodynamic parameters in order to assess which provided the most accurate prognostic information. We can conclude from this study, however, that haemodynamic parameters under stress are more predictive of mortality than resting values.
In a similar study, Tan and Littler [82] studied the application of CPO in patients with acute cardiogenic shock. Twenty eight consecutive patients admitted to the coronary care unit (CCU) with the condition were studied (24 of these patients had sustained a myocardial infarction, MI). Invasive measurements of the haemodynamic parameters were taken, at rest and after dobutamine stress (until no further rise in CPO occurred or a maximum dose of 40 mcg/kg/min was reached). The study showed differences between survivors and non-survivors in resting and maximal LVSWI, maximal CI and maximum CPO. All the patients with a resting CPO <0.35 watts died, as did all the patients with a maximum CPO of <1 watt or a LVSWI <0.25 J/m2.
Over two decades later, the SHOCK trial registry [83] confirmed the prognostic value of resting. In a multivariate analysis, CPO and CPI (cardiac power index) were found to be the only haemodynamic predictors independently associated with in-hospital mortality after adjusting for age and a history of hypertension.
Stress represented by exercise (a more natural physiological index of stress) has also been found to correlate with dobutamine stimulation for maximal CPO [84]. In this study, LVSWI also showed no significant difference between the two modes of stress, but maximal CO values were higher in the dobutamine group. This may have been due to the fact that dobutamine caused more vasodilatation than exercise and the heart converted more of its pressure generating capacity into a flow generating capacity.
Roul and colleagues [74] were the first group to evaluate the prognostic value of peak CPO during maximal exercise testing of patients with CHF. This group assessed 50 patients with NYHA class II-III CHF using invasive measurements of the haemodynamic parameters during maximal supine exercise on a flywheel. The mean follow-up was 21.2±1.17 months. The multivariate analysis revealed the peak CPO to be an independent predictor of death or a major cardiac event and a peak CPO <2 watts was found to accurately identify patients with a poor short term prognosis.

Non-invasive estimation
of cardiac power output

One of the drawbacks of using peak CPO and other haemodynamic parameters as indicators of cardiac function, is that invasive measures use a right heart catheter, which is not without risk to the patient and also impractical for everyday clinical use. Investigators have therefore looked at non-invasive ways of measuring haemodynamic parameters using either echocardiography [85,86] or carbon dioxide (CO2) re-breathing techniques [87]. The non-invasive assessment has the advantage that it does not have the complications associated with Swan-Ganz catherisation, e.g. pneumothorax. From the patients' point of view, it obviates the discomfort associated with in-situ intravenous (± intra-arterial) catheters which can result in indeterminate extents of vaso-vagal reaction. With less constraints, patients are more likely to attain their true maximum exercise capability. Non-invasive measurements are therefore more likely to provide a true reflection of peak exercise haemodynamic data.
Further statistical evidence in favour of using maximal CPO and cardiac reserve (assessed non-invasively by echocardiography) as prognostic indicators was reported by Marmor and Schneeweiss [88]. Forty two patients with CHF (NYHA functional class I-IV) and 10 healthy volunteers were followed-up for 3 years after haemodynamic assessment at rest and after incremental dobutamine stimulation. CPO was estimated non-invasively as the maximal product of systolic pressure and aortic flow. Aortic flow was determined using Doppler ultrasonography to calculate the velocity time integral and aortic cross sectional area. Central aortic pressure was calculated by a computer controlled device producing a non-invasive waveform previously validated against invasive measurements [89]. By aligning the beginning of the flow with the simultaneously recorded central aortic pressure, instant power measurements were obtained. This study showed that those subjects with a cardiac reserve >1.5 watts (i.e. ability to increase cardiac power output on stress) survived and 8 out of the 9 patients with a cardiac reserve <1.5 watts died. Cardiac reserve was found to be the only significant predictor of survival in a multivariate analysis.
That a cut-off point exists for the prognostic power of peak exercise CPO (assessed non-invasively using CO2 re-breathing methods) in a group of patients with stable CHF was confirmed by Williams and colleagues [75]. A cohort of 219 unselected consecutive patients underwent cardiopulmonary exercise testing with non-invasive measurements of haemodynamic parameters over a mean follow up period of 4.64 years. Peak and resting CPO, peak MAP peak and resting CO, and peak VO2 were all predictive of outcome in univariate analyses. Peak CPO, either entered continuously or categorically with a cut-off value of 2.0 watts, was the only independent predictor of mortality using a multivariate model - outperforming peak VO2. The mortality rate of those patients with a peak CPO <2.0 watts was considerably higher than those with a peak CPO >2.0 watts in Kaplan-Meier survival analysis, a result in close agreement with previous published work using invasive measurements of CPO [74].

"Surrogate" markers of cardiac power output
Methods of measuring cardiac output and mean systemic arterial pressures, especially at peak exercise, are not as straightforward as measuring of O2 consumption with available non-invasive equipments nowadays. For practical purposes, approximations to CPO are being sought. After all, VO2 contains CO, multiplied by a factor, the systemic arteriovenous difference in O2 content. At peak exercise, if we can assume that systemic oxygen extraction to be maximal, then the difference in O2 content can be assumed to be relatively constant.
Taking the above into account, Cohen-Solal et al. [90] assessed the prognostic value of a new "surrogate" variable of CPO, "circulatory power" (CircP, the product of peak VO2 and peak systolic blood pressure). Although easier to measure, systolic blood pressures are generally exaggerated in stiffened arterial systems, such as those found in the elderly. Despite these confounders, circulatory power was found to be the only cardiopulmonary variable predictive of prognosis in a population of 175 patients with CHF. Scharf et al. [91] also confirmed the prognostic significance of the circulatory power, which also outperformed peak VO2 in a multivariate analysis, in 154 patients with CHF.
Williams et al. [92] evaluated the relationship between the more direct CPO and the indirect index of cardiac pumping capacity, circulatory power in 219 ambulatory patients with CHF. CircP was found to have a direct and consistent relationship with CPO, both overall and at peak exercise. The results suggest CircP to be an adequate measure of cardiac pumping capacity when the more directly measured CPO is not available. This finding was not unexpected as VO2 contains the term CO, multiplied by a factor, the systemic arteriovenous difference in O2 content
([O2]a-v). For the approximation of CO from VO2 to hold, it requires that we assume at peak exercise the [O2]a-v is invariable, which implies that systemic oxygen extraction is maximal in each patient. If this assumption holds, then peak VO2 and hence peak CircP would provide similar information about cardiac function as peak CO and CPO, respectively.
However, this raises the question whether in clinical practice we can rely on such approximations and assumptions when making important decisions on individual patients, such as whether to undergo cardiac transplantation or not. The answer depends on each clinician's decision about how much trade-off between accuracy and ease of measurement is clinically acceptable. As technology for measuring CO and MAP continuously and non-invasively, especially at peak exercise, is not as well developed as that for measuring VO2, it would therefore seem reasonable to use CircP as a valid and practical surrogate. However, when more critical decision making is required, then the clinician can fall back and rely on the more direct indicator of cardiac function, CPO [15,93].

Cardiac power output
and relationship to exercise capacity

The studies outlined above have highlighted the prognostic importance of CPO, cardiac reserve and the "surrogate" circulatory power, in the assessment of various cardiac disorders. Assessment of exercise capacity and quality of life is as important as mortality in the evaluation of cardiac disease. CPO and cardiac reserve, like peak VO2, have previously been shown to correlate with exercise capacity and quality of life. Bain and colleagues [94] studied 41 CHF patients with NYHA functional class II-IV, using invasive haemodynamic measurements at rest and maximal exercise. Peak exercise CPO was shown to correlate with exercise duration to a greater extent than either maximal cardiac index or left ventricular stroke work index. Cardiac reserve correlated with exercise duration, to a similar extent as peak exercise CPO. A later study by Cooke et al. [87], using non-invasive haemodynamic assessments, was performed to test the hypothesis that CPO and cardiac reserve correlated with peak VO2. Seventy subjects with a wide range of cardiac function, from trained athletes to transplant candidates performed treadmill cardiopulmonary exercise tests with estimation of haemodynamic parameters. CPO at peak exercise was found to correlate significantly with peak VO2. Non-invasive measurements of data were reproducible with coefficients of variation of 4.7% for peak VO2, 7.08% for maximal CO and 9.08% for CPO. Marmor et al. [85] showed NYHA functional class, the classical tool used for symptom assessment of cardiac disorders to significantly correlate with peak CPO, suggesting that NYHA is an easily obtainable clinical surrogate of cardiac function.

Conclusions
Compared to other aspects of cardiology (e.g. coronary artery or valvular diseases, hypertension or arrhythmia), heart failure is conceptually more challenging, and historically, it has also been beleaguered by misleading concepts. At the crux of these difficulties lies the question, what is the most representative measure of cardiac pump dysfunction. To find the answer, we need to acknowledge that heart failure is indeed a disease of exercise intolerance, and that no amount of measurements at basal resting states can accurately depict or predict the true extents of loss of functional reserve. Similarly, any selection of parameter to represent cardiac dysfunction must be cognizant of the fact that the prime role of the mechanical pump is to impart hydraulic energy to maintain an adequate circulation, and that the cardiovascular control system operative in compensating for the failing heart works by detecting the inadequacy of pressure and flow generating capacity of the heart. Evidence available so far supports the concept that there is a central role for measuring cardiac power reserve in understanding how best to evaluate and treat patients with heart failure.
References
1. Tan LB, Williams SG, Goldspink DF. From CONSENSUS to CHARM - how do ACEI and ARB produce clinical benefits in CHF? Int J Cardiol 2004; 94: 137-41.
2. Tan LB, Schlosshan D, Barker D. Fiftieth anniversary of aldosterone: from discovery to cardiovascular therapy. Int J Cardiol 2004; 96: 321-33.
3. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352: 1539-49.
4. Coronel R, de Groot JR, van Lieshout JJ. Defining heart failure. Cardiovasc Res 2001; 50: 419-22.
5. Wood PW. Diseases of the Heart and Circulation. Lippincott, Philadelphia, 1956.
6. Braunwald E. Heart failure: Pathophysiology and treatment. Am Heart J 1981; 102: 486-90.
7. Keogh AM, Baron DW, Hickie JB. Prognostic guides in patients with idiopathic or ischaemic dilated cardiomyopathy assessed for cardiac transplantation. Am J Cardiol 1990; 65: 903-8.
8. Parameshwar J, Keegan J, Sparrow J, Sutton GC, Poole-Wilson PA. Predictors of prognosis in severe chronic heart failure. Am Heart J 1992; 123: 421-6.
9. Clintron G, Johnson G, Francis G, Cobb F, Cohn JN, for the V-HeFT VA Cooperative studies group. Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. Circulation 1993; 87 (suppl. VI): VI-17-23.
10. Benge W, Litchfield RL, Marcus ML. Exercise capacity in patients with severe left ventricular dysfunction. Circulation 1980; 61: 955-9.
11. Franciosa J, Park M, Levine TB. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 1981; 47: 33-9.
12. Higginbotham MB, Morris KG, Conn EH, Coleman RE, Cobb FR. Determinants of variable exercise performance among patients with severe left ventricular dysfunction. Am J Cardiol 1983; 51: 52-60.
13. Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, et al. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA cooperative studies group. Circulation 1993; 87(suppl. VI): VI 5-16.
14. Metra M, Raddino R, Dei Cas. Assessment of peak oxygen consumption, lactate and ventilatory threshold and correlation with resting and exercise haemodynamic data in chronic congestive cardiac failure. Am J Cardiol 1990; 65: 1127-33.
15. Cotter G, Williams SG, Vered Z, Tan LB. Role of cardiac power in heart failure. Curr Opin Cardiol 2003; 18: 215-22.
16. Tan LB, Hall AS. Cardiac Remodelling. Br Heart J 1994; 72: 315-6.
17. Braunwald E, Ross J Jr, Sonnenblick EH. Mechanisms of contraction of the normal and failing heart. Little Brown, Boston, 1968.
18. Sonnenblick EH. Implications of muscle mechanics in the heart. Fed Proc 1962; 21: 975-90.
19. Sonnenblick EH. Force-velocity relations in mammalian heart muscle. Am J Physiol 1962; 202: 931-9.
20. Suga H. Theoretical analysis of a left ventricular pumping model based on the svstolic time varying pressure-volume ratio. IEEE Trans BioMed Engng BME 1971; 18: 47-55.
21. Chatterjee K, De Marco T. Role of nonglycosidic inotropic agents: indications, ethics, and limitations. Med Clin North Am 2003; 87: 391-418.
22. Lehtonen LA. Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory properties. Expert Opin Investig Drugs 2001; 10: 955-70.
23. Thackray S, Easthaugh J, Freemantle N, Cleland JG. The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis. Eur J Heart Fail 2002; 4: 515-29.
24. Felker GM, O'Connor CM. Inotropic therapy for heart failure: an evidence-based approach. Am Heart J 2001; 142: 393-401.
25. Young JB. New therapeutic choices in the management of acute congestive heart failure. Rev Cardiovasc Med 2001; 2: 19-24.
26. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9-13.
27. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344: 1651-8.
28. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353: 2001-7.
29. Harris P. Evolution and the cardiac patient. Cardiovasc Res 1983; 17: 313-9, 373-6, 437-45.
30. Harris P. Congestive cardiac failure: central role of the arterial blood pressure. Br Heart J 1987; 58: 190-203.
31. The consensus trial study group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Co-operative North Scandinavian Study Group (consensus). New Engl J Med 1987; 316: 4129-35.
32. Francis DP, Davies LC, Coats AJS. Diagnostic exercise physiology in chronic heart failure. Heart 2001; 86: 17-20.
33. Osler W. The Principles and Practice of Medicine. Edinburgh: Young J Pentland 1895: 671.
34. Tan LB, Al-Timman JK, Marshall P, Cooke GA. Heart failure: can it be defined? Eur J Clin Pharm 1996; 49 (suppl. 1): S11-8.
35. Myers J, Gullestad L. The role of exercise testing and gas-exchange measurement in the prognostic assessment of patients with heart failure. Current Opin Cardiol 1998; 13: 145-55.
36. Mancini D, LeJemtel T, Aaronson K. Peak VO2 - A simple but enduring standard. Circulation 2000; 101: 1080-2.
37. Morris CK, Ueshima K, Kawaguchi T, Hideg A, Froelicher VF. The prognostic value of exercise capacity: a review of the literature. Am Heart J 1991 122: 1423-31.
38. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. New Engl J Med 2002; 346: 793-801.
39. Szlachcic J, Massie B, Kramer B, Topic N, Tubau J. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 1985; 55: 1037-42.
40. Likoff MJ, Chandler SL, Kay HR. Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or ischaemic cardiomyopathy. Am J Cardiol 1987; 55: 1037-42.
41. Willens HJ, Blevins RD, Wrisley D, Antonishen D, Reinstein D, Rubenfire M. The prognostic value of functional capacity in patients with mild-moderate heart failure. Am Heart J 1987; 114: 377-82.
42. Saxon LA, Stevenson WG, Middlekauff HR, Fonarow G, Woo M, Moser D, et al. Predicting death from progressive heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1993; 72: 62-5.
43. Stevenson LW, Couper G, Natterson B, Fonarow G, Hamilton MA, Woo M, et al. Target heart failure populations for newer therapies. Circulation 1995; 92 (suppl II): II174-81.
44. Haywood GA, Rickenbacher PR, Trindade PT, Gullestad L, Jiang JP, Schroeder JS, et al. Analysis of deaths in patients awaiting heart transplantation: impact on patient selection criteria. Heart 1996; 75: 455-62.
45. Rickenbacher PR, Trindade PT, Haywood GA, Vangelos RH, Schroeder JS, Wilson K, et al. Transplant candidates with severe left ventricular dysfunction managed by medical treatment: characteristics and survival. J Am Coll Cardiol 1996;27:1192-7.
46. Myers J, Gullestad L, Vagelos R, Do D, Bellin D, Ross H, et al. Clinical, hemodynamic and cardiopulmonary exercise test determinants of survival in patients with heart failure. Ann Intern Med 1998; 129: 286-93.
47. Opasich C, Pinna GD, Bobbio M, Sitsi M, Demichelis B, Febo O, et al. Peak exercise oxygen consumption in chronic heart failure: toward efficient use in the individual patient. J Am Coll Cardiol 1998; 31: 766-75.
48. Pardaens K, Van Cleemput J, Vanhaecke J, Fagard RH. Peak oxygen consumption better predicts outcome than submaximal respiratory data in heart transplant candidates. Circulation 2000; 101: 1152-7.
49. Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr, et al. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991; 83: 778-86.
50. Costanzo MR, Augustine S, Bourge R, Bristow M, O'Connell JB, Driscoll D, et al. Selection and treatment of candidates for heart transplantation: a statement for health professionals from the committee on heart failure and cardiac transplantation of the council on clinical cardiology, American Heart Association. Circulation 1995; 92: 3593-612.
51. Smith RF, Johnson G, Ziesche, Bhat G, Blankenship K, Cohn JN. Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The VheFT VA Cooperative Studies Group. Circulation 1993; 87: V188-93.
52. Wilson JR, Hanamanthu S, Chomsky DB, Davis SF. Relationship between exertional symptoms and functional capacity in patients with heart failure. J Am Coll Cardiol 1999; 33: 1943-7.
53. Loeb HS, Johnson G, Henrick A, Smith R, Wilson J, Cremo R, et al. Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalisation in patients with chronic congestive cardiac failure. The VheFT VA Cooperative Studies Group. Circulation 1993; 87: V178-87.
54. Fleg JL, Lakata EG. Role of muscle loss in age-associated reduction in VO2 max. J Appl Physiol 1988; 65: 1147-51.
55. Becklake MR, Frank H, Dagenais GR, Ostiguy GL, Guzman CA. Influence of age and sex on exercise cardiac output. J Appl Physiol 1965; 20: 938-47.
56. Wasserman K, Hansen JE, Sue DY, Whipp BJ, Casburi R. Principles of Exercise Testing and Interpretation. Lea and Fabiger, 1994.
57. Cohen?Solal A, Barnier P, Pessione F, Seknadji P, Logeart D, Laperche T, et al. Comparison of the long term prognostic value of peak exercise oxygen pulse and peak oxygen uptake in patients with chronic heart failure. Heart 1997; 78: 572?6.
58. Myers J, Gullestad L, Vagelos R, Do D, Bellin D, Ross H, et al. Cardiopulmonary exercise testing and prognosis in severe heart failure: 14 mls/kg/min revisited. Am Heart J 2000;139:78-84.
59. Weber KT, Kinasewitz GT, Janicki JS, Fishman AP. Oxygen utilisation and ventilation during exercise in patients with chronic cardiac failure. Circulation 1982; 65: 1213-23.
60. Meiler SE, Ashton JJ, Moeschberger MC, Unverferth DV, Leier CV. An analysis of the determinants of exercise performance in congestive heart failure. Am Heart J 1987; 113: 1207-17.
61. Kelly TL, Cremo R, Nielsen C, Shabetai R. Prediction of outcome in late?stage cardiomyopathy. Am Heart J 1990; 119: 1111?21.
62. Ghali JK, Kadakia S, Bhatt A, Cooper R, Liao Y. Survival of heart failure patients with preserved versus impaired systolic function: the prognostic implication of blood pressure. Am Heart J 1992; 123: 993-7.
63. De Groote P, Millaire A, Decolouix E, Nugue O, Guimier P, Ducloux G. Kinetics of oxygen consumption during and after exercise in patients with dilated cardiomyopathy. J Am Coll Cardiol 1996; 28: 168-75.
64. Osada N, Chaitman BR, Miller LW, Yip D, Cishek MB, Wolford TL, et al. Cardiopulmonary exercise testing identifies low risk patients with heart failure and severely impaired exercise considered for heart transplantation. J Am Coll Cardiol 1998; 31: 577-82.
65. Pousset F, Masson F, Chavirovskaia O, Isnard R, Carayon A, Golmard JL, et al. Plasma adrenomedullin, a new independent predictor of prognosis in patients with chronic heart failure. Eur Heart J 2000; 21: 1009-14.
66. Robbins M, Francis G, Pashkow F, Snader CE, Hoercher K, Young JB, et al. Ventilatory and heart rate responses to exercise. Better predictors of mortality than peak oxygen consumption. Circulation 1999; 100: 2411-7.
67. Francis DP, Shamim W, Davies LC, Pieopli MF, Ponikowski P, Anker SD, et al. Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from the VE/VCO2 slope and peak VO2. Eur Heart J 2000; 21: 154-61.
68. Florea VG, Henein MY, Anker SD, Francis DP, Chambers JC, Ponikowski P, et al. Prognostic value of changes over time in exercise capacity and echocardiographic measurements in patients with chronic heart failure. Eur Heart J 2000; 21: 146-53.
69. Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 2001; 103: 967-72.
70. Cohen-Solal A, Laperche T, Morvan D, Geneves M, Caviezel B, Gourgon R. Prolonged kinetics of recovery of oxygen consumption after maximal graded exercise in patients with chronic heart failure. Analysis with gas exchange measurements and NMR spectroscopy. Circulation 1995; 91: 2924?32.
71. Griffin BP, Shah PK, Ferguson J, Rubin SA. Incremental prognostic value of exercise haemodynamic variables in chronic congestive heart failure secondary to coronary artery disease or dilated cardiomyopathy. Am J Cardiol 1991; 67: 848-53.
72. Metra M, Faggiano P, D'Aloia A, Nodari S, Gualeni A, Raccagni D, et al. Use of cardiopulmonary exercise testing with haemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure. J Am Coll Cardiol 1999; 33: 943-50.
73. Chomsky DB, Lang CC, Rayos GH, Shyr Y, Yeoh TK, Pierson III RN, et al. Haemodynamic exercise testing: A valuable tool in the selection of transplantation candidates. Circulation 1996; 94: 3176-83.
74. Roul G, Moulichon ME, Bareiss P, Gries P, Koegler A, Sacrez J, et al. Prognostic factors of chronic heart failure in NYHA class II or II: value of invasive exercise haemodynamic data. Eur Heart J 1995; 16: 1387-98.
75. Williams SG, Cooke GA, Wright DJ, Parsons WJ, Riley RL, Marshall P, et al. Peak exercise cardiac power output: A direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure. Eur Heart J 2001; 22: 1496-503.
76. Barringer TB. The circulatory reaction to graduated work as a test of the hearts functional capacity. Arch Int Med 1917; 17: 363.
77. Rushmer RF. Cardiovascular Dynamics. Philadelphia: W.B. Saunders, 1970
78. Tan LB. Cardiac pumping capability and prognosis in heart failure. Lancet 1986; ii: 1360-3.
79. Tan LB. Clinical and research implications of new concepts in the assessment of cardiac pumping performance in heart failure. Cardiovasc Res 1987; 21: 615-22.
80. Tan LB. Evaluation of cardiac dysfuncton, cardiac reserve and inotropic response. Postgrad Med J 1991; 67 (suppl 1): S10-20.
81. Franklin KJ. A short history of physiology. London: Bale, 1933.
82. Tan LB, Littler WA. Measurement of cardiac reserve in cardiogenic shock: implications for prognosis and management. Br Heart J 1990; 64: 121-8.
83. Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, et al. SHOCK Investigators. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol 2004; 44: 340-8.
84. Tan LB, Bain RJI, Littler WA. Assessing cardiac pumping capability by exercise testing and inotropic stimulation. Br Heart J 1989; 62: 20-5.
85. Marmor A, Raphael T, Marmor M, Blondheim D. Evaluation of contractile reserve by dobutamine echocardiography: non-invasive estimation of the severity of heart failure. Am Heart J 1996; 132: 1195-201.
86. Armstrong GP, Carlier SG, Fukamachi K, Thomas JD, Marwick TH. Estimation of cardiac reserve by peak power: validation and initial application of a simplified index. Heart 1999; 82: 357-64.
87. Cooke GA, Marshall P, Al-Timman JK, Wright DJ, Riley R, Tan LB. Physiological cardiac reserve; development of a non-invasive method and first estimates in man. Heart 1998; 79: 289-94.
88. Marmor A, Schneeweiss A. Prognostic value of non-invasively obtained left ventricular contractile reserve in patients with severe heart failure. J Am Coll Cardiol 1997; 29: 422-8.
89. Sharir T, Mamor A, Ting CT. Validation of a method for non-invasive measurement of central aortic pressure. Hypertension 1993; 21: 74-82.
90. Cohen-Solal A, Tabet JY, Logeart D, Bourgoin P, Tokmakova M, Dahan M. A non-invasively determined surrogate of cardiac power (circulatory power) at peak exercise is a powerful prognostic factor in chronic heart failure. Eur Heart J 2002; 23: 806-14.
91. Scharf C, Merz T, Kiowski W, Oechslin E, Schalcher C, Brunner-La Rocca HP. Noninvasive assessment of cardiac pumping capacity during exercise predicts prognosis in patients with congestive heart failure. Chest 2002; 122: 1333-9.
92. Williams SG, Tzeng BH, Barker D, Tan LB. Comparison and relationship of indirect and direct dynamic indices of cardiac pumping capacity in chronic heart failure. Am J Cardiol - in press (05/05).
93. Nicholls DP, O'Dochartaigh C, Riley MS. Circulatory power - a new perspective on an old friend. Eur Heart J 2002; 23: 1242-5.
94. Bain RJI, Tan LB, Murray RG, Davies MK, Littler WA. The correlation of cardiac power output to exercise capacity in chronic heart failure. Eur J Appl Physiol 1990; 61: 112-8.
Copyright: © 2005 Termedia & Banach. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2020 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe