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.


Costs and Benefits of the Fenestrated vs. Non-fenestrated Fontan Procedure


The Fontan procedure was developed so that the heart could function and distribute oxygenated blood around the body without the need for two ventricles. As I have discussed previously (see here and here), today the Fontan procedure is done through a lateral tunnel/intra-cardiac route or an extra-cardiac route. Here is a nice image depicting what these two procedures look like.

The Fontan Operation
Extra-cardiac Fontan on the right and Fenestrated intra-cardiac/lateral tunnel Fontan on the left.
In the lateral tunnel/intra-cardiac route for the Fontan procedure, a piece of plastic (‘baffle’)  is built in the right atrium to direct the deoxygenated blood coming from the lower part of the body (via the inferior vena cava) to go directly to the lungs. One major development that was first described in 1990 to refine the lateral tunnel/intra-cardiac Fontan was the creation of a small hole called a ‘fenestration’ in the baffle during the Fontan procedure (Bridges et al., 1990, Circulation 82, 1681-1689). As the image below shows, a small hole/fenestration is created in the baffle in the right atrium (indicated by the arrow with #2)..

diagram 2.23 - Stage 3 of hypoplastic left heart syndrome reconstruction

This image highlights the fenestration (small hole) created in the baffle in the right atrium (indicated by #2 with arrow).

This ‘fenestrated Fontan’ as it is commonly called today was described by Bridges et al. (1990). The goal of the fenestration was to try and lower the risk of mortality in the period of time soon after the Fontan surgery. At that time, high blood pressure in the right atrium (where the baffle was placed) and low cardiac output (basically the total amount of blood pumped by the heart) was a predictor of mortality in the post-operative period. That is, patients with high blood pressure in the right atrium or low cardiac output were more likely to die soon after surgery. Bridges et al. (1990) proposed that some of this pressure in the right atrium could be ‘relieved’ and cardiac output increased by creating a small hole in the baffle in the right atrium. They thought that this fenestration would relieve some of this pressure and increase cardiac output, which could potentially decrease mortality rates soon after the surgery. However, of course this fenestration would also cause right-to-left shunting where deoxygenated blood in the right atrium mixes with oxygenated blood in the single ventricle, which would of course lower blood oxygen concentrations leaving the heart. Bridges et al. (1990) proposed and treated patients with these fenestrated Fontan’s by closing the hole in the baffle during a heart catheterization 3-12 months after the Fontan surgery or letting the hole close spontaneously on its own.

How Common is the Fenestrated Fontan?

The creation of a fenestration in the baffle during both lateral tunnnel/intra-cardiac or extra-cardiac Fontan procedures is now extremely common. For example, from 1992-2002, of all the Fontan procedures (using both techniques) performed in 7 different hospitals where Fontan procedures are commonly performed (part of the Pediatric Heart Network), over 80% of them created a fenestration (Atz et al., 2011, J of American College of Cardiology 57, 2437-2443). This is not surprising given that the use of a fenestration in the baffle during a Fontan procedure has many positive short-term outcomes (see list below).

Short-term Costs and Benefits of a Fenestrated Fontan

1) Patients with a fenestrated Fontan have a shorter duration of chest-tube drainage. In a well-designed randomized study by Lemler et al. (2002, Circulation 105, 207-212), the authors show that patients at the Children’s Medical Center of Dallas that underwent a fenestrated Fontan (25 patients) had significant drainage from chest tubes (that is post-operative pleural effusions) for an average of 10 days (range was 5-62 days) whereas patients that underwent a non-fenestrated Fontan (24 patients) had significant drainage from chest tubes for an average of 16 days (range 3-45). Similarly, patients that had a fenestrated Fontan had significantly less total drainage from the chest tubes (measured in volume) than those that underwent the non-fenestrated Fontan. This study supports an earlier one by Bridges et al. (1992, Circulation 86, 1762-1769) that also shows that the duration of chest tube drainage is reduced by using a fenestrated Fontan procedure in high-risk patients.

2) Patients with a fenestrated Fontan have a shorter length of hospital stay after the surgery but no difference in time spent in the intensive care unit. Bridges et al. (1992) and Lemler et al. (2002) both show that patients that underwent a fenestrated Fontan procedure stayed in the hospital after the Fontan procedure for a shorter amount of time than those that underwent the non-fenestrated Fontan. For example, Lemler et al. (2002) showed that patients that underwent the fenestrated Fontan stayed in the hospital after the surgery for an average of 12 days (range was 6-26 days) whereas those that underwent the non-fenestrated Fontan stayed in the hospital after the surgery for an average of 23 days (range was 5-64 days). In contrast, the use of a fenestration didn’t affect how long patients spent in the intensive care unit after the Fontan.

3) Patients with a fenestrated Fontan have lower oxygen saturations after the surgery. As mentioned above, a major benefit of the fenestrated Fontan is that cardiac output (amount of blood pumped by the heart) is increased but this comes at a cost of the mixing of deoxygenated blood from the right atrium with oxygenated blood in the single ventricle. For example, Lemler et al. (2002) found that patients with a fenestrated Fontan had significantly lower oxygen saturations in the post-operative period (average of 90%) compared to those with a non-fenestrated Fontan (average of 93%). Though, it should be noted that the range of oxygen saturations in the non-fenestrated group was quite high (66-98%) compared to the fenestrated group (81-96%) suggesting that the difference when looking at averages was much higher if the patient with an oxygen saturation of 66% was dropped from the analysis.

5) Patients with a fenestrated Fontan were taking more medications at hospital discharge compared to those with a non-fenestrated Fontan. Atz et al. (2011) found that patients with a fenestrated Fontan (361 patients) were more likely to be taking an ACE inhibitor (e.g., captopril or enalapril) and anti-thrombotic drugs (e.g., asprin, warfarin) at hospital discharge after the Fontan than those that had a non-fenestrated Fontan (175 patients). However, this could be because of differences among the hospitals such as one hospital always performing fenestrated Fontan’s and always providing patients with an ACE inhibitor and asprin at discharge.

6) Do patients with a fenestrated Fontan have an increased risk of stroke? It has been suggested that patients with a fenestrated Fontan may have an increased risk of stroke, though this hasn’t been supported by previous studies. For example, one of the first studies (du Plessis et al. 1995 Pediatric Neurology 12, 230-236) documenting this potential increased risk of stroke from a fenestrated Fontan showed that of the total of 314 that underwent the Fontan procedure at the Boston Children’s Hospital from 1989-1993, a total of 209 patients had a fenestrated Fontan. Out of all of these patients, 10 of them had a stroke where 9 out of 209 patients with a fenestrated Fontan (4.3%) compared to only 1 patient with a non-fenestrated Fontan having a stroke (1/105 patients or 0.95%). This difference was not statistically significant and it also reflects that patients in the fenestrated Fontan group may have already been at a higher risk for stroke prior to the procedure. More recent studies, however, do not find that patients with a fenestrated Fontan have an increased risk of stroke compared to patients with a non-fenestrated Fontan (e.g., Coon et al., 2001, Annals Thorac Surg 71, 1990-1994; Atz et al., 2011).

Long-term Costs and Benefits of a Fenestrated Fontan?

Although the fenestrated Fontan is commonly used today, whether or not it is used seems to be highly dependent upon where the Fontan procedure is done. For example, the percentage of patients that had a fenestrated Fontan can vary from 13-91% at 7 major hospitals in North America  (Atz et al., 2011). That is highly variable! Why might some surgeons always perform fenestrated Fontan’s while others choose not to create a fenestration during the Fontan procedure especially when there are such obvious short-term benefits during the post-operative period?

Well, what do we actually know about the long-term costs and benefits of a fenestrated Fontan? As mentioned above, the creation of the fenestration allows the deoxygenated blood from the right atrium to mix with the oxygenated blood in the single ventricle, which consequently can lower blood oxygen concentrations that leave the heart. Some researchers have suggested that the use of a fenestration is not a preferred option for some surgeons because there is little scientific evidence that it is beneficial in the long-term (Gersony (2008, Circulation 117, 13-15; de Laval and Deanfield 2010, Nature Reviews Cardiology 7, 520-527). This is primarily because the long-term impacts of a fenestrated Fontan are relatively unknown. Let’s look at what we do know about the long-term impacts of a fenestrated Fontan. In a recent study by Atz et al. (2011), they compared the medical status of patients that had underwent a fenestrated Fontan where the fenestration was either still open or had been closed (either spontaneously or during a heart catheterization).

1) Patients with a fenestrated Fontan may have an increased risk of death, stroke, heart transplant, etc. from 1-10 years after the Fontan procedure compared to those with a non-fenestrated Fontan. Tweddell et al. (2009, Ann Thorac Surg 88, 1291-1299) compared the fate of patients that underwent either a fenestrated Fontan (217 patients) or a non-fenestrated Fontan (38 patients) from 1994-2007 at the Children’s Hospital of Wisconsin. For these 38 patients, the fenestration that was originally present was closed in the operating room based upon the judgement of the surgeon. Interestingly, Tweddell et al. (2009) found that the patients with the fenestrated Fontan had a higher incidence of Fontan failure compared to those with a non-fenestrated Fontan. Here, Fontan failure was basically defined as the patient dying, needing a heart transplant or pacemaker, developing protein-losing enteropathy, or having a stroke. From 0-4 years of after the Fontan procedure, the incidence of Fontan failure was similar between patients with fenestrated and non-fenestrated Fontan’s. However, around 4 years after the Fontan procedure had been performed, patients with a fenestrated Fontan tended to have a higher incidence of Fontan failure. Although this study cannot confirm that fenestration resulted or caused this increase in Fontan failure, it is a highly interesting result given how often the fenestrated Fontan is performed.

2) Patients with a fenestrated Fontan have lower resting oxygen saturations than those in which the fenestration is closed. Atz et al. (2011) showed that of patients with a fenestrated Fontan (hole did not spontaneously close or wasn’t closed during a heart catheterization) had significantly lower oxygen saturations (average was 89%) compared to patients in which the fenestration was closed (average of 95%). This suggests that in terms of increasing blood oxygen saturations, closing the fenestration may be beneficial (see also Goff et al., 2000, Circulation 102, 2094-2099).

3) Few other long-term costs of a fenestrated Fontan have been documented. Atz et al. (2011) found that patients with a current fenestration compared to those with a closed fenestration did not differ in their overall health status, exercise performance, occurrence of stroke or protein-losing enteropathy, or body growth. Moreover, a previous study supports some of these results where patients with a fenestrated Fontan had a similar exercise capacity as did those with a non-fenestrated Fontan (Meadows et al., 2008, J Am Coll Cardiol 52, 108-113). This contrasts those results from Tweddell et al. (2009) at least in terms of documenting why patients with a fenestrated Fontan may have a higher incidence of Fontan failure. Essentially, there were few differences between patients with fenestrated and non-fenestrated Fontan’s.

Should the Fenestration be Closed?

Atz et al. (2011) found that around 40% of 361 patients that underwent a fenestrated Fontan had their fenestration close spontaneously. Many doctors recommend closing the fenestration at some time interval after the Fontan procedure. There may be specific benefits for closing the fenestration related to blood oxygen saturations. For example, Goff et al. (2000) found that 154 patients that underwent successful closure of the fenestration during a heart catherization had an increase (9.4% on average) in oxygen saturation when measured from 0.4-10.3 years after the fenestration closure. As indicated above, Atz et al. (2011) also found that patients in which the fenestration was closed also had higher blood oxygen saturations. These increases in blood oxygen saturations may be associated with favorable outcomes for body growth. For example, Goff et al. (2000) found that patients in which the fenestration was closed rose in their height and weight percentiles compared to what they were prior to closing the fenestration suggesting that closing the fenestration is associated with an increased rate of body growth. On the other hand, Atz et al. (2011) did not really find that there was many benefits associated with closing the fenestration other than increasing blood oxygen saturations. So is it worth it to have the fenestration closed? The current evidence suggests that there are some major benefits in terms of increasing blood oxygen saturations but few other benefits. Obviously this needs more study and we cannot make conclusions based upon one study.

Conclusion. It is somewhat surprising that most patients that undergo the Fontan procedure now have a fenestrated Fontan regardless of whether they have an intra-cardiac/lateral tunnel or extra-cardiac Fontan. This is surprising because although a fenestrated Fontan obviously has beneficial outcomes in the short-term (reducing duration and amount of chest tube drainage, reduced hospital stay), we still know very little about the long-term consequences of a fenestrated Fontan. In fact, some have now questioned whether fenestrations should always be performed and advocated the adoption of a patient-specific approach where only ‘high-risk’ patients undergo a fenestrated Fontan (Gersony, 2008). Second, the evidence is not clear regarding whether we should always be closing the fenestration later in life or even when the fenestration should be closed (i.e., how many years after the Fontan?). Some have even argued that closing the fenestration during a heart catheterization is not worth the risks even if they are low (discussed in Goff et al., 2000) and this is not surprising because the evidence at present doesn’t show that there are substantial benefits of closing the fenestration other than increases in blood oxygen saturations (Atz et al., 2011). Not discussed at length here is the fact that the presence of a fenestration can increase cardiac output (Bridges et al., 1990), which could decrease after the fenestration is closed. Given that the use of a fenestrated Fontan is highly variable among different hospitals (Atz et al., 2011), it seems wise to be informed about the potential short- and long-term costs and benefits of having a fenestrated vs. non-fenestrated Fontan. Clearly more work needs to be done here.

Lateral tunnel versus extracardiac conduit Fontan procedure: a concurrent comparison

In this paper by Kumar et al. (2003, Ann Thorac Surg 76, 1389-1397), the authors compare the outcomes of patients that underwent the Fontan procedure either using the intra-cardiac (lateral tunnel) or extra-cardiac conduit method. I have previously discussed the differences of these two types of the Fontan procedure here. and how the use of each type has changed over time here. In brief, the intra-cardiac or lateral tunnel method is the ‘older’ method (introduced in 1987) and the extra-cardiac method was more recently developed (1990). The lateral tunnel/intra-cardiac method involves sewing a piece of plastic inside the right atrium to route all blood from the lower part of the body (via the inferior vena cava) to the lungs whereas the extra-cardiac method involves placing a tube (either a tissue graft or plastic) outside the heart so that all blood from the lower part of the body (again via inferior vena cava) goes to the lungs. Regardless, some hospitals still perform the intra-cardiac method is the preferred option (see here).

The first thing to point out that this study was published over 10 years ago and uses data from patients that underwent the Fontan procedure from 1995-2002. As I have discussed elsewhere, there have been significant improvements in patient care and outcomes from the Fontan procedure. The other issue that these authors indicate is that most institutions only use one of the types of Fontan or they have suddenly changed over time. As such, it is hard to compare the outcomes of a lateral tunnel vs. extra-cardiac Fontan at a single hospital over the same time period. This study presents data where they performed both lateral tunnel (37 patients) and extra-cardiac (33 patients)  Fontan procedures at the same institution (Medical University of South Carolina) at the same time period.

Summary of Major Points of this Paper:

1) Theoretical advantages of extra-cardiac method. The lateral tunnel or intra-cardiac method requires placing a piece of plastic (“baffle”) inside of the atrium. The lateral tunnel/intra-cardiac method has had good early, medium, and long-term outcomes as well in previous follow-up studies. However, this requires sewing the piece of plastic (Gore Tex) inside the heart, which may increase the risk of atrial arrhythmias. The extra-cardiac method avoids having to sew this piece of plastic inside of the heart and so a theoretical advantage is that this method may decrease risk of future heart rhythm issues. However, note that this generally requires that the surgery be performed later in life because you are placing a piece of plastic in the heart that will not grow with the patient. Another possible advantage of the extra-cardiac method is that it can allow surgeons to perform the procedure without aortic cross-clamping (where they prevent the blood from leaving the heart) and even without cardiopulmonary bypass, which may have some advantages for short- and long-term outcomes (discussed here). For example, in this study, aortic cross clamping was always used for the lateral tunnel/intra-cardiac method but used in ~51% of patients for the extra-cardiac method.

2) No difference in time on cardiopulmonary bypass between intra-cardiac and extra-cardiac method but patients undergoing intra-cardiac method were on aortic cross clamping longer than those using extra-cardiac method. Patients undergoing the lateral tunnel/intra-cardiac method were on bypass (mean = 134 min) nearly the same amount of time as those undergoing the extra-cardiac method (mean = 145 min). However, 100% of patients undergoing the lateral tunnel/intra-cardiac method had aortic cross-clamping and for a longer period of time (mean = 55 min) than those that had the extra-cardiac method (52% of patients, mean = 26 min).

3) No difference in time on ventilator, time in intensive care unit, duration of chest tube drainage, and hospital stay between those having the lateral tunnel/intra-cardiac method vs. those undergoing the extra-cardiac method. This is an interesting result given that the lateral tunnel/intra-cardiac method is theoretically supposed to improve short-term outcome (that soon after the surgery) because of decreased chest tube drainage, etc. However, here they didn’t find any differences between the two methods.

4) No difference in type or frequency of medications given to patients that underwent intra-cardiac vs. extra-cardiac Fontan ~3 years previous. Though this probably attributable to the hospital itself and how they treat their patients, most of the patients were on asprin (94%) and there were no other differences between the type of frequency of medications taken between patients that underwent intra-cardiac or extra-cardiac method ~3 years previous.

5) No difference in heart rhythm problems between patients that had underwent intra-cardiac vs. extra-cardiac Fontan at ~3 years after the surgery. This is somewhat surprising that 15% of patients that had underwent the intra-cardiac Fontan ~3 years previous had heart rhythm issues (sinus node dysfunction) whereas MORE (28%) of patients that had underwent the extra-cardiac Fontan had heart rhythm issues ~3 years previous. Although this is not statistically different, this is opposite than what would be expected. Two patients underwent permanent pacemaker implantation (1 lateral tunnel and 1 extra-cardiac method) and in one case for slow junctional rhythm.

6) No difference in the post-operative blood pressure in various parts of the atrium and in the Fontan pathway (“Fontan pressure” and transpulmonary gradient) between patients that underwent the intra-cardiac vs. extra-cardiac Fontan. The authors provide brief discussion how these pressures can be predictive of early Fontan failure but they found no difference between these two methods in the first 24 hours after the Fontan.

Summary: This study highlights the lack of any real differences between the intra-cardiac/lateral tunnel vs. extra-cardiac Fontan in both the short- and long-term. This study also highlights the low rates of mortality or Fontan takedown (4.3%) around and soon after the actual surgery and high rates of survival 3-5 years after the Fontan for both the intra-cardiac (97%) and extra-cardiac (91%) methods.

The authors discuss their results in light of other studies that were contemporary at the time of this publication (2003). There results are similar to those of Gaynor et al. (2001, J Thorac Cardiovasc Surg 121, 28-41) who reported results from patients undergoing either intra- or extra-cardiac Fontan at Children’s Hospital of Philadelphia (1992-1999) and who again found no real differences between the methods. However, in another previous study that did a similar comparison between patients that underwent the intra-cardiac or extra-cardiac method at the Hospital for Sick Children in Toronto (data from 1994-1998), there was a significantly higher incidence of heart rhythm problems for patients undergoing the lateral tunnel/intra-cardiac method (45%) than those that underwent the extra-cardiac method (15%) at the post-operative period. Why the differences? The authors indicate that it may come from how the Fontan procedure was staged. The second surgery prior to the Fontan is either the hemi-Fontan procedure or the bidirectional Glenn shunt. The authors indicate that they selectively perform the hemi-Fontan for patients that were to undergo the lateral tunnel/intra-cardiac Fontan and perform the bidirectional Glenn shunt for patients that are due to undergo the extra-cardiac Fontan. In contrast, the patients at the hospital in Toronto were all staged with the bidirectional Glenn shunt regardless of whether they were to undergo the intra-cardiac or extra-cardiac Fontan (well, all patients except 1). The authors discuss how the hemi-Fontan (2nd surgery) prior to the lateral tunnel Fontan is a preferred option than doing the bidirectional Glenn shunt prior to the lateral tunnel Fontan (as the surgeons in Toronto did) because the latter involves making incisions in the same area where the previous incisions for the bidirectional Glenn shunt were made. Cutting into the same places where previous incisions were made in the sinus node region is probably not a preferable option. Interesting result. These findings confirm other studies that the risk of heart rhythm issues is higher for patients that underwent the bidirectional Glenn shunt prior to the lateral tunnel/intra-cardiac Fontan than if they had underwent the hemi-Fontan prior to the lateral tunnel/intra-cardiac Fontan. I wonder if all hospitals now always do the hemi-Fontan before the lateral tunnel/intra-cardiac method now?

Finally, the authors discuss how sometimes one method has to be done over another because of other issues with the heart anatomy. In other words, the choice of an intra-cardiac vs. extra-cardiac Fontan is not randomized among patients. For example, the lateral tunnel Fontan is often done for patients with hypoplastic left-heart syndrome but the extra-cardiac method is preferred for patients with heterotaxy syndrome. This makes it difficult to assess whether the short-, medium, or long-term outcomes are a result of the surgical procedure itself (i.e., which Fontan method) or the actual underlying condition.

Link to this paper:


Fontan circulation: success or failure?

In this paper by Mondesert et al. (2013, Canadian Journal of Cardiology) critically review the putative success of the Fontan procedure that is commonly used to treat children (and adults) with complex congenital heart defects such as hypoplastic right or left heart syndrome and so on. This is a fantastic review and opinion by these Canadian researchers that highlights the difficulties associated with the Fontan circulation and discusses avenues for future research. What I found most revealing is that they highlight the “bad news” or potential complications, which is a big contrast to our experience with pediatric cardiologists or cardiothoracic surgeons that sometimes highlight only the “good news” of the Fontan procedure. Success can favor those who are prepared and it is important to be aware of these potential complications resulting from the Fontan circulation and also emphasize the need for more research in treating congenital heart defects.

I also think that this paper has a great overview (with diagrams) of the Fontan circulation showing the different variations of the Fontan procedure: 1) modified classic version, 2) intracardiac lateral tunnel, and 3) extracardiac tunnel.

Here are some interesting points from this paper:

1) The Fontan does not cure patients with congenital heart defects. The Fontan procedure was first introduced in 1971 and it is obviously a life saving procedure that many children (and parents) have benefited from. However, as you would suspect given that the Fontan procedure is a type of “palliative care”, it doesn’t “cure” or “fix” the congenital heart defect. You might almost view it as a bridge to another surgery or even another health complication. However, it is quite amazing that the current rate of death around the time of the Fontan (soon after) is <2%.

2) Those with the Fontan circulation do not have ‘normal’ heart physiology or functioning. Two major complications that might have many “downstream” effects are the following effects on increasing (“hypertension”) and decreasing (“hypotension”) blood pressure depending upon its location (veins or arteries). First, with Fontan circulation, there is “systemic venous hypertension”, which means that the blood pressure in the veins (blood going back to the heart) in the body is higher than in individuals with normal heart function (not Fontan circulation). There are many negative consequences that may be caused by systemic venous hypertension (congestive heart failure, edema or swelling, dysfunction of the liver, potentially protein-losing enteropathy) that are basically related to the distribution of fluids in the body. A second complication is “pulmonary arterial hypotension” where the blood pressure in arteries going towards or in the lungs (hence pulmonary) is lower than in individuals with normal heart function. There are also a number of negative consequences associated with pulmonary arterial hypotension such as cyanosis (blue lips!) or lack of exercise capacity. As this paper summarizes, many of the subsequent medical conditions and deaths that follow the Fontan procedure (either in the short- or long-term) are thought to originate from this change in systemic and pulmonary blood pressure.

3) Patients that undergo the Fontan procedure have limited lifespans (enjoy them now). In those that survive the Fontan procedure (and probably released from the hospital), 90% survive or do not need a heart transplant 10 years post-Fontan, whereas these numbers drop to 83% 20 years post-Fontan, and 70% 25 years post-Fontan. This study declares that one type of Fontan (i.e., modified classic, intracardiac lateral tunnel, or extracardiac tunnel) has not been associated with higher survival or success of patients. But surely because some of these techniques have been used for varying amounts of time we need more study to confirm this. All of this information about the causes of death following the Fontan procedure is reported in Khairy et al. (2008, Circulation 2008;117:85-92)

4) Individuals that had the Fontan procedure most often die from heart failure, stroke (thrombosis), or some unexplained sudden death. Of note is the fact that the risk of death from heart failure is quite low within 10 years of the Fontan procedure but increases with time after 10 years post-Fontan.

5) A few risk factors associated with increased risk of death or need for heart transplant are highlighted. A) One risk factor that seems to be important in predicting death or need for a heart transplant is the development of atrial tachycarrhythmias (meaning some heart rhythm problem where the heart is beating too fast), patients with these rhythm problems may have a higher risk of death. B) Second, the risk of death from a stroke or thrombosis increases dramatically 15 years post-Fontan yet the use of antiplatlet or anticoagulation therapy (asprin or warfarin, respectively) was associated with a decrease in the risk of death from stroke. C) Patients that developed protein-losing enteropathy, only had the right ventricle (e.g., hypoplastic left heart syndrome), or had increase blood pressures had a higher risk of death.

6) Not surprisingly, as time passes from the date of the Fontan procedure, the risk of death or need from a heart transplant increases. The authors note that this could be from some sudden death or heart failure, but it could also be from a gradual decline in heart function that is hard to document. Obtaining detailed health profiles from patients with Fontan circulation over their lifetime might help reveal early indicators associated with a heightened risk of death later in life.

How does the Fontan fail? The authors describe and summarize three different ways or categories in which the Fontan can “fail” (that is the patient dies or needs a heart transplant). Here is a summary:

1) The first category that they use is “ventricular dysfunction” where the ejection of the blood out of the heart (remember, ventricles eject blood!) or the blood pressure inside the heart becomes abnormal. This maybe is not surprising given that patients with the Fontan circulation have only one ventricle that is doing the work of two. This is a good reason why heart catheter procedures are performed so that these blood pressures inside the heart can be documented. One way to treat such ventricular dysfunctions is through drugs such as enalapril that can affect ventricular function. However, these authors indicate that benefits for administering enalapril are not entirely clear and they may actually depend upon whether the patient has hypoplastic right or left heart. A more recent drug that has been proposed to treat this ventricular dysfunction is sildenafil (viagra). In trials with adults that had heart failure and children that had the Fontan procedure, administering sildenafil increased some measures of ventricular performance. However, more studies are needed here.

2) The second category in which the Fontan can fail is through “systemic complications”, which are those where the altered Fontan circulation affects other parts of the body negatively. i) First, patients that need the Fontan often have low oxygen saturations in their blood (cyanosis) and this can persist even after the Fontan. In particular, in fenestrated Fontan procedure where a small hole is made in the patch of material put inside the heart to alter circulation (which can increase survival soon after the Fontan), oxygen saturations may remain lower for some time after the Fontan. This chronic cyanosis could have other pervasive effects on the body. The authors suggest that surgical intervention to close the fenestration might be necessary in some cases. It does seem like much more work about the long-term complications of the fenestrated Fontan are needed.

ii) Because of the altered Fontan circulation, many patients develop liver (hepatic) dysfunction. As was indicated above, patients with Fontan circulation have systemic venous hypertension and what a few studies have found summarized in this paper is that patients with Fontan circulation have venous pressures in or near their liver that may be 3-4 times higher than normal. Over the long-term, this hepatic dysfunction may have some major negative consequences but this is far from understood. However, in the autopsy of patients with Fontan circulation, many of them show signs of liver cirrhosis or other characteristics associated with liver dysfunction. In many cases, the authors indicate, the negative effects of hepatic dysfunction (which start right after the Fontan) are not apparent until 10 years after the Fontan. One future area of research is to identify early signs of hepatic dysfunction potentially using non-invasive measures such as levels of particular metabolites in the blood ore presumably also in the urine or feces. Unfortunately, there is as of yet no real promising avenues to treat hepatic dysfunction in patients with Fontan circulation. However, the authors do indicate that drugs that lower systemic venous pressure could be beneficial and also that combined heart and liver transplant is an option.

iii) Patients with Fontan circulation often die from stroke or thrombosis. This is likely caused by many factors such as changes in blood flow or even the placement of a synthetic material in the heart. Identifying all of the risk factors associated with death from thrombosis is another area of research. Interestingly, the authors state that another study shows that risk of death from thrombosis is similar for patients with the intra-cardiac lateral tunnel or extra-cardiac tunnel (Robbers-Visser et al., 2010 Eur J Cardiothorac Surg 2010;37:934-41) yet there is still no consensus on whether the use of anticoagulation (warfarin) or antiplatelet (asprin) substances are necessary (Canter 2011, J Am Coll Cardiol 2011;58:652-3).

iv) Protein-losing enteropathy has to be the worst diagnosis a patient with the Fontan circulation can receive. PLE essentially means that important proteins are lost and there are many swellings of particular areas of the body. The worst part about it is that it can come on very quick but it can also develop slowly.  The authors indicate that the most common early symptom of PLE is that a child complains their clothes or shoes don’t fit and sometimes they have diarrhea. Doctors than confirm PLE by finding low levels of protein or albumin in the blood and finally showing that a particular protein produced by the liver is excreted in the feces at a high concentration. Why it occurs in some patients with Fontan circulation but not others is not really clear but nonetheless 3-10% of patients with Fontan circulation develop PLE. The causes of PLE are not really known but the low oxygen saturations in the gut may underlie PLE. Treating PLE is complicated and include increasing cardiac output, administration of drugs that are anti-inflammatory (heparin, steroids), or a combination of budesonide (steroid) and sildenafil (again, viagra).

v) Similar to PLE, plastic bronchitis is also a scary but rare side-effect of the Fontan circulation (<1-2% of patients develop it). Airways become obstructed by debris and other substances and the linings of the lungs become inflamed and swell. The cause of plastic bronchitis is also unknown but might be similar to the cause of PLE. Treating plastic bronchitis is still largely experimental and involves drugs used for asthma (inhaled steroids) or mechanical clearing of the obstructions. Cardiac transplantation can also improve the outcome.

vi) Many patients have heart arrhythmias afther the Fontan procedure (the authors say up to 40% of patients). Normal sinus rhythm is disrupted by the Fontan procedure and a fast (tachyarrhythmias) or slow (bradyarrhythmias) can result. The obvious treatment for these heart rhythm problems is to implant a pacemaker or treat through other means such as ablation or drugs (for tachyarrhythmias). The authors indicate that the current consensus indicate that patients with an intra-cardiac lateral tunnel Fontan have a similar risk of developing an arrhythmia as patients with the extra-cardiac Fontan (cite a variety of studies especially Khairy and Poirier, 2012, Circulation 126,2516-2525). Patients that are older at their Fontan procedure tend to have a higher risk of developing heart rhythm problems. Somewhat scarily, atrial tachyarrhythmias may not be very obvious and may cause sudden death, so surveillance for these rhythm problems is important.

3) Now we come to the final category of how patients with the Fontan circulation can die. The final way that may be the most pernicious is through chronic deterioration. As the years tick by after the Fontan procedure, heart function gets worse, which is reflected in the decline in the ability to do aerobic exercise. For example, for patients that had the Fontan early in life, they may have exercise capacity that is highly reduced (44%) compared to normal patients and this capacity to do exercise tends to decline in a linear fashion each year (declines 2.6% each year). At thirty years of age, patients with Fontan circulation have much reduced exercise capacity (55% less than normal) and the number of health problems and hospitalization rates increase dramatically. This is probably not surprising since, again, one ventricle is doing the work of two. How could we increase or preserve cardiac function with age? One way is through drugs such as a recent study showing that children given sildenafil (viagra) for 6 weeks have improved exercise capacity compared to those not given the drug (Goldberg et al., 2011, Circulation 2011;123:1185-93). The obvious solutions are heart transplantation, but again, because the Fontan circulation has already wreaked havoc in the body such as negatively affecting hepatic or kidney function. So patients with Fontan circulation may still be in poor shape even after a heart transplant. The final, seemingly far-fetched, option is to use a mechanical device that assists the heart. As mentioned above, ventricular dysfunction increases with time since Fontan, which could cause chronic failure of the Fontan. One way to improve survival is to use mechanical devices (“Fontan assist device”) that assist blood flow out or into the heart. For example, mechanical devices that increase arterial blood pressure or decrease venous pressure. This is an interesting topic but the authors say that these devices hold promise but only in the distant future.

Link to this paper:


18 years of the Fontan operation at a single institution

In this study by Dr. Lindsay S. Rogers et al. (2012, Journal of the American College of Cardiology 60, 1018-1025), the authors report their experiences of performing the Fontan operation (palliation) on 771 patients from 1992-2009 at the Children’s Hospital of Philadelphia. The authors recorded a variety of variables about the patient (demographic and anatomical) and the actual surgical procedure (e.g, time on cardiopulmonary bypass, amount of drainage from the pleural – chest – tubes, length of stay, readmission to the hospital following the procedure) and report their findings here.

The interesting part of this study is that they split their analysis into 3 different ‘eras’. Era 1 were Fontan operations performed from 1992-1997 (6 years), Era 2 was 1998-2002 (5 years), and Era 3 was 2003-2009 (7 years). This is important because how patients with a congenital heart defect born in 1992-1993 that had the Fontan procedure may have been treated much differently than those born in 2007-2008 that exhibited the same defect and had the same Fontan procedure. Obviously we hope that science and medical research in general should advance how we treat human diseases and how we perform operations and so it is predicted that outcomes for those born in Era 3 (2003-2009) that had the Fontan procedure may have higher survival rates than those born in Era 1 (1992-1997). This study highlights the shift in treating children with congenital heart defects among these three eras. For example, as the authors indicate, Era 1 (1992-1997) represents a time period when most children were treated with the lateral tunnel type of Fontan (see #1 below for an introduction to this point) , during Era 2 (1998-2002), there was a shift towards using the extra-cardiac conduit method (but still relatively equal number of both method) and routine use of the “modified ultrafiltration” method of cardiopulmonary bypass (see link below) started during this Era 2 (in 1996), and in Era 3 most Fontan operations were performed using the extra-cardiac conduit method (though note that this differs from other hospitals such as C.S. Mott Children’s Hospital – see below). Again, this study highlights the importance of allowing researchers to use such data gathered from children having the Fontan procedure as it allows these types of analyses.

Here are the major findings or those that I find interesting:

1) As Fig. 1 indicates, the number of Fontan procedures performed per year at this hospital ranges from 25-70, not terribly high and somewhat surprising to me. It also shows how the type of Fontan performed has changed dramatically across these years. In Era 1 (1992-1997), most Fontan procedures had the lateral tunnel method whereas in the modern era (2003-2009), most Fontan procedures used the extra-cardiac conduit method. From what I understand, the lateral tunnel method is older (well, introduced in 1987) than the extra-cardiac conduit method (introduced in 1990). The lateral tunnel (LT) procedure involves placing a ‘baffle’ (piece of Gore-tex) inside the atrium. One predicted risk of the LT procedure is an increased chance of developing heart rhythm problems, which might not be surprising given that you are sewing something inside of the atrium. The LT procedure is still used by many major hospitals (e.g., at C.S. Mott Children’s Hospital at the University of Michigan, 92% of Fontan procedures performed from 1992-2007 used the LT method: Hirsch et al. 2008, Annals of Surgery 248, 402-410). The extra-cardiac conduit (literally outside the heart tunnel…) or ECC method basically does not involve sewing this baffle into the atrium and is theoretically associated with decreased postoperative complications. This topic (lateral tunnel vs. ECC) should clearly be a focus of a future blog post as I have a major interest in this area. Moving on…

2) From Era 1 (1992-1997), the median age at Fontan was 2.3 years, whereas it was 2.8 years in Era 3 (2003-2009). This is somewhat surprising given our personal experiences that the age of Fontan has been steadily decreasing over the years. Also, as these authors show, the age at stage 2 surgery (e.g., “hemi-Fontan”) decreased from Era 1 (6.4 months) to Era 3 (5.9 months). It would be interesting to conduct a more fine-grained analysis where we look at how differences in age at Fontan affect other parameters (e.g., do children that have Fontan at 18 months have a different outcome than those at 36 months?). As far as I can tell, most studies that have looked at this break the data up into larger chunks (e.g., Fontan performed >3 years or ❤ years as in Shiraishi et al. (2009, Annals Thoracic Surgery 87, 555-561). In this study by Shiraishi et al. (2009), they found that patients with dominant left ventricle (e.g., having Tricuspid atresia or a very small/reduced right ventricle) that had the Fontan procedure performed before 3 years of age had a higher cardiac index (basically heart performance corrected for variation in body size) at 5 and 10 years after operation and higher peak oxygen consumption (might view this as exercise capacity).

On the other hand, this increase in age at Fontan from Era 1 to Era 3 is likely due to the observation that body weight at the time of the Fontan procedure is a predictor of short- and long-term outcomes. Indeed, weight at Fontan from Era 1 (12 pounds) has increased to Era 3 (12.9 pounds).

3) Perhaps the most important part of this paper is the “outcomes” section. The good news is that only 3.5% of the patients that underwent the Fontan procedure died from 1992-2009 (27/771) and the probability of death of the individual <30 days after the Fontan procedure has declined significantly from Era 1 (9.3% died) to Era 3 (1.2%), though there hasn’t been any improvement in increasing survival <30 days after the Fontan from Era 2 (1.0%) to Era 3 (1.2%).

4) More good news is that duration in the ICU, total time in the hospital, and the frequency of lengthy (>14 days)  pleural effusions (drainage from the chest tubes) has declined from Era 1 to Era 3. Though the average i) ICU duration (2-3 days across Era 1 to Era 3) has not changed from 1992-2009, the variation has changed such that were fewer lengthy stays in the ICU in Era 3 (range of stay was 1-45 days) compared to Era 1 (0-181 days). Similarly, the duration of chest tube drainage in Era 1 (mean was 3 days) was similar to Era 3 (4 days) but again the frequency of chest tube drainage that lasted >14 dyas has declined from Era 1 (28.6%) to Era (17.5%). Moreover, the length of hospital stay has declined from Era 1 (12 days) to Era 3 (8 days) and the frequency of lengthy hospital stays (>14 days) after the Fontan has declined from Era 1 (46.7% of Fontan procedures performed here involved patients staying >14 days after procedure) compared to Era 3 (19.5% patients stayed >14 days after Fontan).

5) The final and important part of this paper is indicating the risk factors that predicted whether patients that had the Fontan procedure died, had lengthy hospital stays or chest tube drainage after the Fontan. For death or Fontan takedown within 30 days of the Fontan procedure, those patients that had longer times on deep hypothermic circulatory arrest had an increased probability of dying or Fontan takedown. However, the use of modified ultrafiltration during cardiopulmonary bypass has decreased the risk of death or Fontan takedown, which again is good news and evidence that progress in surgical techniques has benefited patients having the Fontan procedure performed in the modern era. This also highlights the importance of asking your surgeon or their support team how long your child was on cardiopulmonary bypass as it provides some potentially useful information about the future or risks for the future. Also of note, whether patients had the i) lateral tunnel or extra-cardiac conduit method of the Fontan and ii) whether fenestration was or was not used did not affect the risk of death or Fontan takedown within 30 days of the Fontan, though this is again only 30 days after the Fontan and we need to know more about the long-term outcomes of these different procedures.

6) Because the authors found that those patients with longer support times (basically longer cardiopulmonary bypass time) had longer hospital stays and longer periods of chest tube drainage after the Fontan, they also investigated what factors of the patient affected total support time. They found that patients that were larger at the Fontan had longer total support times and that those patients that had the extra-cardiac conduit method also had longer total support times. These are interesting results when comparing the benefits and costs of the lateral tunnel vs. extra-cardiac conduit method as well as the age (and weight) at which to perform the Fontan procedure. However, the longer total support time and the longer time on deep hypothermic circulatory arrest (see above) likely just reflect that the surgery was more complicated because of a complex heart defect. The authors do indicate that their results suggest that the extra-cardiac conduit method is associated with greater short-term complications (longer chest tube drainage and hospital stay duration because of longer total support time) but the preferential use of this procedure over the lateral tunnel method is because it is thought to lower the risk of long-term complications (heart rhythm problems associated with lateral tunnel methods). Yet, we need to see those data showing a reduction in heart rhythm problems in order to justify the conclusion that the extra-cardiac conduit method has long-term benefits compared to the lateral tunnel method!

7) The final and interesting point of this paper is found in Table 9, which summarizes the post-operative outcomes from several similar studies using data collected from several hospitals that commonly perform these procedures (e.g., Children’s Hospital of Philadelphia, C.S. Mott Children’s Hospital at the University of Michigan, Children’s Mercy Hospitals and Clinics in Kansas City, Children’s Hospital of Wisconsin, Children’s Hospital in Boston,  etc.). What is interesting here is that you might make some comparisons among the different studies (and really hospitals) for mortality rates, hospital stay times, bypass times, etc. Though I will resist making comparisons here because really it isn’t good science to make comparisons when the hospitals and surgeons take in different numbers of patients (some do more than others) and take in patients with varying degrees of difficulty (who may have higher mortality rates). For example, at the Children’s Mercy Hospitals and Clinics in Kansas City, surgeons performed 145 Fontan procedures (all nonfenestrated, extra-cardiac conduit method) from 1997-2008 and 5.5% of those patients died and 2.8% of those patients had Fontan takedown. In contrast, at Children’s Hospital of Wisconsin in Milwaukee, surgeons performed 256 Fontan procedures (fenestration used selectively) from 1994-2007, 2.0% of those patients died and 0.8% of those patients had Fontan takedown. These differences may or may not be statistically different from one another and we do not know if the degree of complexity of the defects treated at the two hospitals differ from one another.

Link to this paper:


Link to information about Modified Ultrafiltration during cardiopulmonary bypass:


A 43- to 54-year follow-up of 1000 patients with congenital heart disease

In this paper by Drs. James H. Moller and Ray C. Anderson (The American Journal of Cardiology, 2013, in press, see link below), the authors followed the survival of 994 patients with various congenital heart defects that were evaluated in 1952-1963. These patients were seen by these doctors early in life (infancy or childhood) and then they were followed into adulthood, which is now a time period of 43-54 years! The authors have published similar follow-up studies in the past such as a follow-up ranging from 26-37 years following the initial diagnosis.

This study is not an experiment but simply an observational study where they simply measure various health metrics at regular checks. It may be helpful in predicting what trajectory your child or adult might follow depending upon their condition but remember that in this study, these children were diagnosed in 1952-1963. Luckily for children born more recently that have similar heart defects today, their treatment and diagnosis may be much more advanced and refined than the children that were diagnosed in 1952-1963. I enjoy these types of ‘follow-up’ papers because they help to remove some of the cloud of confusion or lack of clarity on the future for children born today with congenital heart defects.

As the authors indicate, it is surprising and encouraging that ~64% of these patients that were born from 1952-1963 were still alive >50 years after their initial diagnosis. This is encouraging because we can only hope that the treatment for children with the same conditions that are born today will have even higher probabilities of survival due to improved and refined treatment. These types of papers are also important for parents with children with congenital heart defects as well as adults living with congenital heart defects because they demonstrate the importance of voluntarily enrolling in such follow-up studies so that more data and patterns can be identified.

Here is a quick summary of some of the major results of this paper:

1) Around 63% of patients were alive almost 50 years later and risk of death declines after surviving first 10 years of life. This study was based at the Departments of Medicine and Pediatrics at the University of Minnesota in Minneapolis. The authors report information about survival from 994 patients that were diagnosed with a congenital heart defect from 1952-1963. Of these 994 patients, 63.6% (632) were alive as of 31 December 2006 (apparently the date of the last evaluation). For those patients that had died, most of the deaths (57.7% or 209/362 patients) occurred in the first 10 years of life with many (34.5% or 125/362 patients) occurring in their first year of life. For those that survived past 10 years of age, the rate of death was relatively equal for patients in their 20’s, 30’s, 40’s, 50’s, and 60’s (7-10% died in each decade of life). Although it would be preferable to have even lower rates of death, it is interesting to note that the rate of death is about equal for those that reached 20 years of age.

2) Around 1/3 of patients died from cardiac issues. The authors report the cause of death for 130 adult patients (I think this means those that survived until at least 20 years of age, though this is not clear). Perhaps importantly, 40% of these deaths were from non-cardiac issues (cancer, accidents, diabetes, suicide, etc.). For those patients that died through cardiac issues, sudden death was the most common cause (~27%) with congestive heart failure, death while waiting for heart transplant, myocardial infarction (heart attach), cardiac reoperation, etc. having similar frequencies.

3) The probability of survival from birth to 10, 20, 30, 40, 50, 60 years of age was markedly lower for patients that are cyanotic (low oxygen saturations). How cyanosis was measured and the cut-off for the cyanotic group versus the other group is not clear to me.

4) Patients with only a ventricular septal defect, patent ductus arteriosus, or an atrial septal defect (no other condition) actually had a similar probability of survival to normal patients from 0-60 years of age. However, patients that had one of these three conditions plus another defect (not clear what they mean by ‘other anomalies’ here) had a much lower probability of survival from 0-60 years of age.

Link to this paper: