Exercise capacity: a predictor of mobidity and mortality?

In this paper by Diller et al. (2010, European Heart Journal 31, 3073-3083), the authors report the outcomes of 321 patients that underwent the Fontan procedure from 1997-2008 in four major hospitals in Europe.

The Importance of Exercise Capacity in Patients with Congenital Heart Defects

One of the major advancements of this study was that the authors not only recorded the fate of these patients but they also measured exercise capacity of these patients to see whether it affected their probability of dying, needing a heart transplant, or risk of hospitalization. This is an important advancement because recent studies have suggested that exercise capacity for patients with congenital heart defects (including those that have undergone the Fontan procedure) can be predictive of future survival as well as future medical issues.  For example, in 335 adult patients with various congenital heart defects (average age 33 years), exercise capacity was much lower than other individuals of the same age and was actually similar to adult patients that had heart failure that was not caused by a congenital heart defect (Diller et al., 2005, Circulation). By exercise capacity, I mean maximal oxygen consumption (“VO2 maximum”) that is measured during a cardiopulmonary exercise test that takes place on treadmill. Other traits during exercise are also measured of course but VO2 maximum is thought to reflect the overall physical condition (especially cardiovascular condition) and capacity for physical exertion of an individual. For example, VO2 maximum is very high in endurance athletes like runners or cyclists. This early study by Diller et al. (2005) was surprising because many adult patients with congenital heart defects did not report to the investigators that they actually experienced limitation during exercise or other periods of physical exertion yet they clearly showed it in their depressed VO2 maximum values.

In this study by Diller et al. (2010), the authors located 321 patients from Europe with various congenital heart defects that had the Fontan procedure 1997-2009 in 4 hospitals in Europe (German Heart Center in Munich, Royal Brompton Hospital in London, University Hospital in Bologna, and Great Ormand Street Hospital in London). They performed cardiopulomonary exercise testing to measure VO2 maximum and a variety of other characteristics reflecting exercise capacity during a standardized exercise trial on a treadmill. They followed these patients for an average of 21 months after exercise testing, though some patients were followed as short as <14 months and others >42 months. They recorded whether these patients were hospitalized, died, or underwent heart transplantation.

Major Findings of this Study by Diller et al. (2010)

1) Exercise capacity (VO2 maximum) was not affected by whether patients had the lateral tunnel/intra-cardiac Fontan or the extra-cardiac Fontan. Though it is important to note that a formal statistical analysis was not presented here.

2) VO2 maximum during exercise testing was highly reduced compared to normal patients. As expected and other studies have found (see below), VO2 maximum during exercise was highly reduced compared to what would be expected for a patient at that same age without the Fontan procedure. Actually only <3% of patients had what would be considered a normal exercise capacity (VO2 maximum) based upon the calculations of the authors.

3) VO2 maximum was not significantly related to probability of death or need for heart transplantation but heart rate reserve was. Unlike previous studies (see below), VO2 maximum was not related to the probability of death or need for a heart transplant but patients with lower heart rate reserve (which is the peak heart rate during exercise minus the resting heart rate) had a higher chance of dying or needing a heart transplant during follow-up. However, it is important to note that relatively few patients died (22 patients out of 321) or needed a heart transplant (6 patients out of 321) so these comparisons might not be the best given you are comparing the physiological values of one very small group (28 patients) compared to another much larger group (283 patients). Also, when the authors compared patients that were followed for a minimum of 3 years, they found that there was no effect of exercise capacity on probability of death or need for cardiac transplantation.

4) Patients with low exercise capacity (low VO2 maximum, low heart rate reserve, etc.) were more likely to be hospitalized during follow-up. The authors found that 41% of patients were hospitalized for a heart related issue during the follow-up period. Those patients with low VO2 maximum during exercise testing and low heart rate reserve (again peak heart rate during exercise minus resting heart rate) were more likely to be hospitalized for a heart related issue during follow-up.

Summary of Effects of Exercise Capacity on Survival and Health of Patients with Congenital Heart Defects

This study by Diller et al. (2010) adds to the growing number of studies showing that patients with congenital heart defects that ALSO exhibit low capacity for aerobic exercise tend to fare poorly. For example, in separate studies using different patients, Diller et al. (2005) found that adult patients with low exercise capacity (low VO2 maximum) tended to be more likely to be hospitalized or die in the year following exercise capacity testing (see also Dimopoulos et al., 2006 Circulation 113, 2796-2802). In a later study but with a longer follow-up time after testing of exercise capacity (28 months after testing), those with low exercise capacity (again low VO2 maximum) had a higher probability of dying in the subsequent 28 months (Diller et al., 2006 J American Coll of Cardiology 48, 1250-1256). In this same study by Diller et al. (2006), the authors also found that patients whose heart rates didn’t respond appropriately to exercise (i.e., dramatically increase immediately following the start of exercise) had a higher probability of dying in the subsequent 28 months. These studies along with the results from Diller et al. (2010) that I discussed above strongly link the  inability of the heart to perform properly during exercise for patients with congenital heart defects is unfortunately linked with an increased risk of future medical complications (reflected in increased hospitalization rates for heart related issues) or death.

Obviously these results don’t suggest that a low VO2 maximum or low heart rate reserve or other marker of exercise capacity is equivalent to an increased risk of death for ALL patients. One question that I have based upon these studies is what is known about the effects of preventative care for patients with congenital heart defects? For example, to conclusively test that exercise capacity does in fact contribute itself to increased risk of death or hospitalization rather than simply reflecting overall poor condition, future studies would need to identify groups of patients with variable exercise capacity. If half of these patients did moderate and regular exercise like walking that might increase exercise capacity, would they fare better than the other half that did not engage in such moderate exercise? I don’t know but that would be interesting to identify if we can improve outcomes by increasing exercise capacity. The major goal here would be to see how we can increase exercise capacity and that has beneficial outcomes in the short- and long-term. Interestingly, recent studies where patients with the Fontan physiology were provided with sildenafil (viagra) showed increased exercise capacity (e.g., Giardini et al., 2008 European Heart Journal 29, 1681-1687). Obviously this needs much more study to understand the costs and benefits of administering sildenafil to patients with Fontan physiology. However, this is currently a promising and interesting start to understanding if increasing exercise capacity lowers the risk of hospitalization or probability of death.

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