Exercise Testing In Defining Prognosis In Heart Failure

Most investigators have found that pVo2 is the best indicator of prognosis in patients with heart failure. This well established variable can be thought of as integrating a number of factors which determine the severity of heart failure and the degree of functional limitation including cardiac reserve, skeletal muscle function, pulmonary abnormalities, and endothelial dysfunction.3

Peak Vo2 correlates poorly with haemodynamic factors measured at rest which is consistent with the fact that these resting parameters do not reflect functional reserve. There is, however, a good correlation between maximum cardiac output and pVo2.4

The factors that appear to be important in determining pVo2 are outlined in table 9.3.

The measurement of pVo2 was first described by Webber and colleagues as a method for characterising cardiac reserve and functional status in heart failure.5 Subsequently pVo2 has been shown by a number of investigators to be of prognostic significance, with lower pVo2 predicting mortality and the need for cardiac transplantation. For example, Szlachcic and colleagues studied 27 patients with heart failure and reported a 77% one year mortality rate in those with pVo2 <10 ml/kg/ min and 21% mortality rate in those with pVo2 between 10-18 ml/kg/min.6 A further study of 201 heart failure patients found that pVo2 was an independent predictor of mortality.7 Many other studies have confirmed these findings.

Cardiac transplantation is an important and successful treatment for end stage heart failure but its major limitation continues to be a shortage of appropriate donors. Therefore, accurate selection of those patients who will benefit most from transplantation is important. In this regard exercise parameters, in particular pVo2, have been found to be very important. Measurement of pVo2 in the assessment of subjects for cardiac transplantation is now endorsed within guidelines.8

In a widely quoted study Mancini and colleagues reported on 116 patients who were referred for assessment for cardiac transplantation (fig 9.2).9 Thirty five of the patients had a pVo2 of < 14 ml/kg/min; these patients were accepted for cardiac transplantation. A further 52 patients had a pVo2 > 14 ml/kg/ min and in these subjects transplantation was deferred. In addition to these two groups, a further 27 patients had pVo2

< 14 ml/kg/min but had other comorbidities which meant that they were not suitable for cardiac transplantation. one year survival in those with pVo2 > 14 ml/kg/min was 94%, while in those with pVo2 below this cut-off in whom transplantation was not carried out because of comorbidities, survival at one year was only 47%. In the subjects with pVo2

< 14ml/kg/min accepted for transplantation, one year survival while waiting for transplantation was 70%, and if urgent transplantation was counted as death one year survival was reduced to 48%. one year survival of 24 patients with a pVo2

< 14 ml/kg/min after transplantation was 83%. These results clearly demonstrate that low pVo2 identified a group of heart failure patients at high risk of death or need for urgent transplantation and that those subjects with higher pVo2 could have transplantation deferred.

Attempts have been made to use percentage of predicted pVo2 to improve the prognostic power of this measure. Percentage of predicted pVo2 may account for factors such as age, sex, and muscle mass which may have a significant impact on pVo2. In a study of 272 patients referred for transplantation, subjects were divided by strata of pVo2 uptake and percentage of predicted pVo2.10 These strata were designed to be of similar size. In this study survival curves were found to be similar whether the strata were classified by pVo2 or percentage of predicted pVo2. others have found that percentage of pVo2 is a better prognostic marker than pVo2, with 50% of predicted pVo2 the most significant predictor of death.11 It is likely that in some patients, percentage of pVo2 would be more useful—for example, at the extremes of age and possibly in women.

Table 9.2 Response to exercise in cardiac versus pulmonary disease

Variable

Cardiac disease

Pulmonary disease

Peak Vo2

Heart rate reserve

Anaerobic threshold

Oxygen pulse

Vo2 workload ratio

Peak Pao2 or O2 saturation

Reduced Usually none

Reduced (<40% predicted)

Reduced

Reduced

Normal

Reduced Increased

Normal or not achieved

Normal

Normal

Decreased

Peak Vo2, peak oxygen uptake; Heart rate reserve, difference between predicted maximum heart rate and attained heart rate with maximum exercise; Oxygen pulse, O2 uptake divided by heart rate, represents O2 extracted by the tissues from O2 carried in each stroke volume; Vo2 workload ratio, represents the efficiency of muscular work; Pao2, arterial oxygen tension.

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