Ann Thorac Surg 2003;76:848-852
© 2003 The Society of Thoracic Surgeons
Original article: cardiovascular
After repair, atrioventricular valve regurgitation during cardiac extracorporeal membrane oxygenation predicts survival
Tiffanie R. Johnson, MDa*,
Marcus S. Schamberger, MDa,
James C. Hart, BSNb,
Mark W. Turrentine, MDc,
John W. Brown, MDc
a section of Pediatric Cardiology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA,
b section of Neonatology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA
c Department of Surgery, Section of Cardiothoracic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
Accepted for publication March 20, 2003.
* Address reprint requests to Dr Johnson, Department of Pediatrics, Section of Pediatric Cardiology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Riley Research 104, 702 Barnhill Dr, Indianapolis, IN, USA 46202-5225
e-mail: tifjohns{at}iupui.edu
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Abstract
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BACKGROUND: When echocardiography is used to follow up cardiac patients on extracorporeal membrane oxygenation (ECMO), ejection fraction as a measure of ventricular function has been used to determine likelihood of survival after decannulation. We hypothesized that systemic atrioventricular (AV) valve regurgitation while on ECMO may be a better predictor of survival.
METHODS: From February 1995 to March 2001, 64 patients required ECMO postoperatively. Three were removed from ECMO owing to brain death, so 61 patients formed our study group. Retrospective chart review was performed with systemic AV valve regurgitation and ejection fraction while on ECMO recorded from echocardiography reports. Patients alive 1 month after decannulation were considered survivors.
RESULTS: There were 29 survivors (47.5%). Ejection fraction in survivors (mean 41% ± 0.13%) was not significantly different from that of nonsurvivors (41% ± 0.18%; p 
0.839) but severity of systemic AV valve regurgitation was significantly different. Only 2 survivors (6.8%) had at least moderate AV valve regurgitation compared with 17 of the 32 nonsurvivors (53%). Patients with moderate to severe regurgitation while on ECMO were less likely to survive for 1 month after decannulation, with an odds ratio of 16.63 (95% confidence interval 3.08, 89.70; p = 0.001). Also female sex increased the odds of death by a factor of 5.43 (95% confidence interval 1.45, 20.36; p = 0.012).
CONCLUSIONS: Severity of systemic AV valve regurgitation on ECMO is a more reliable predictor than ejection fraction for survival at 1 month after decannulation. Patients with less than moderate AV valve regurgitation have a significantly better chance of survival.
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Introduction
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Extracorporeal membrane oxygenation (ECMO) has been used as mechanical cardiopulmonary support for children with severe respiratory or heart failure from various causes for nearly 3 decades [1]. Children may require cardiac support with ECMO after cardiac surgery immediately or within a few hours or days owing to ventricular dysfunction from various causes. Early studies have justified the use of ECMO as an effective means of support for postoperative cardiac failure refractory to medical management and as a lifesaving measure for patients who would otherwise not survive [2–5]. More recent studies have evaluated numerous clinical variables for impact on survival when ECMO is used for cardiac reasons [6–8]. Few studies have included evaluation of echocardiographic variables that may be useful in predicting patient survival when ECMO is used for cardiac support after heart surgery. With the increasing use of ECMO after repair of congenital heart defects, reliable echocardiographic predictors of survival are needed.
Traditionally ejection fraction as a measure of ventricular function has been used to determine the capability of the heart to provide an adequate cardiac output and thus patient survival after ECMO decannulation. Systemic atrioventricular (AV) valve regurgitation is usually noted during the echocardiogram performed while the patient is on ECMO but the usefulness of this variable as an indicator of ventricular function and patient survival is unknown. We hypothesized that while on ECMO severity of systemic AV valve regurgitation may be a better predictor of patient survival than ejection fraction.
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Material and methods
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A retrospective review of patient charts was performed after obtaining approval from the Indiana University Institutional Review Board. The study period was from February 1995 through March 2001. During this time 3,562 pediatric cardiac surgeries (1,705 open heart procedures, 1,857 closed heart procedures) were performed at Riley Hospital for Children, Indiana University, and there were 64 cases ([1.8%] 62 open heart procedures [3.6%] and 2 closed heart procedures [0.1%]) in which ECMO was used postoperatively for mechanical cardiac support. Three patients removed from ECMO owing to brain death were excluded from analysis and the remaining 61 patients formed our study group. (See Table 1 for the list of patient diagnoses). Patients were grouped as cardiac survivors and nonsurvivors. They were considered cardiac survivors if they were still alive 1 month after ECMO decannulation. One patient who survived after receiving a heart transplant was considered a cardiac nonsurvivor.
With support required in the postoperative period, patients underwent venoarterial cannulation through the mediastinum. Techniques for managing the ECMO circuit were similar to what has been reported previously in the literature. A servoregulated flow system driven by a roller pump with a membrane oxygenator (Medtronic ECMO Membrane Oxygenator; Medtronic, Minneapolis, MN) was used with premembrane and postmembrane in-line pressure monitors. A disposable heat exchanger maintained constant temperature of blood in the circuit and the priming volumes of the circuit were determined by the surface area of the oxygenator, based on the patient’s size. A continuous heparin infusion was used to maintain activated clotting times between 180 and 200 seconds or lower if significant bleeding occurred.
Echocardiographic reports of all patients performed while they remained on ECMO support were reviewed specifically for the amount of systemic atrioventricular valve regurgitation and ejection fraction. Regurgitation was a qualitative evaluation, which was then graded with an absolute number from 0 to 4 (0 = none, 1 = trivial, 2 = mild, 3 = moderate, 4 = severe). If multiple echocardiograms were performed while a patient was on ECMO the report with the most severe amount of systemic AV valve regurgitation was used. The measured ventricular ejection fraction was recorded as a percentage (%). Assessments of AV valve regurgitation and ejection fraction were determined by the pediatric cardiologist who generated the original echo report at the time the echo was performed. Thus the pediatric cardiologist was naturally "blinded" to eventual patient outcome. The amount of preoperative systemic AV valve regurgitation was recorded in the same fashion. Information regarding demographics and ECMO support (flow, hours on ECMO, inotropic support, and so forth) surrounding the time of the echocardiogram was also recorded. Inotropic support was a three-tiered scale from minimal (1) to moderate (2) to maximal (3): 1 = one continuous inotropic drip at low to moderate dosage or two at low dosage, 2 = two or more continuous inotropic drips with at least one at moderate or higher dosage, and 3 = two or more continuous inotropic drips with at least two or more at moderate dosage. All variables were analyzed for 1-month survival after ECMO decannulation. Variables analyzed are listed in Table 2.
Statistical analysis was performed using SPSS for Windows version 11.0.1 (SPSS, Chicago, IL). Quantitative variables were reported as the mean ± SD. The outcome of interest was survival to 30 days; hence survival was treated as a binary variable rather than analyzing time to death. Comparisons between survivors and nonsurvivors were analyzed using Fisher’s exact test for discrete variables. Continuous variables that were not normally distributed were analyzed with the Mann-Whitney U test and the Wilcoxon signed rank test. Forward stepwise logistic regression with all variables univariately related to survival was used to determine which ones were independently related to 1-month survival. A value of p less than 0.05 was considered significant.
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Results
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The 61 patients in our study group consisted of 35 male and 26 female subjects with a mean age of 7.0 months (range, 0 to 85.8). The cardiac defects of these patients were quite diverse (Table 1), but only 15 patients had single ventricle physiology. Of these 61 patients requiring ECMO for postoperative mechanical cardiac support from February 1995 to March 2001, 29 patients (47.5%) survived at least 1 month after ECMO decannulation. For those who did not survive, death occurred an average of 3 days after removal from ECMO. Although this ranged from 0 to 17 days, the median was 1 day after removal from ECMO. Ejection fraction while on ECMO in survivors (mean, 0.41 ± 0.13) was not significantly different from that of nonsurvivors (0.41 ± 0.18; p 0.839). However the severity of systemic AV valve regurgitation was significantly different between the two groups. Only 2 of the 29 survivors (6.8%) had at least moderate AV valve regurgitation compared with 17 of the 32 nonsurvivors (53%). Patients with moderate to severe regurgitation while on ECMO were less likely to survive (p < 0.001) for 1 month after ECMO decannulation. Moderate to severe regurgitation increased the odds of death by a factor of 16.63 (95% confidence interval: 3.08, 89.70; p = 0.001; Fig 1).
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Fig 1. Percentage of survivors (shaded bars) compared with nonsurvivors (black bars) at each level of atrioventricular (AV) valve regurgitation. The majority of survivors were in the categories with less than moderate regurgitation. No patients with severe regurgitation survived.
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No significant difference existed in the amount of AV valve regurgitation preoperatively between survivors (score of 0.86 ± 0.92) and nonsurvivors (1.17 ± 1.12; p = 0.293). However for all patients regurgitation was significantly lower preoperatively (1.05 ± 1.02) than during ECMO (1.85 ± 1.30; p < 0.001). When compared with all other patients, those with abnormal systemic AV valve anatomy (including all atrioventricular canal [AVC] defects, n = 8) did not differ significantly in the amount of regurgitation preoperatively (normal, 0.96 ± 1.03; abnormal, 1.43 ± 0.98; p = 0.248) or during ECMO (normal, 1.81 ± 1.33; abnormal, 2.19 ± 1.10; p = 0.546). There was also no significant difference in survival between these two groups (p = 0.260).
There was a significant difference in survival based on sex. Twenty-two of the 35 male patients (62%) and 7 of the 26 female patients (27%) survived for at least 1 month after ECMO decannulation. Being female increased the odds of death by a factor of 5.43 (95% confidence interval: 1.45, 20.36; p = 0.012). Forward stepwise logistic regression showed that both of these significant variables (severity of AV valve regurgitation and sex) contributed independently to failure to survive (Table 3).
Other variables analyzed surrounding the time that the echocardiogram was done were not significant (Table 2). Age and body surface area were not significant factors for likelihood of survival. The mean duration of ECMO support for survivors was 129 ± 62 hours; for nonsurvivors it was 164 ± 132 hours (p = 0.464). Mean length of time on ECMO at the time the echocardiography was performed was 70.4 ± 56.4 hours for survivors compared with 98.9 ± 108.5 hours for nonsurvivors and was not significantly different between the two groups (p = 0.426). The amount of ECMO circuit flow at the time the echocardiogram was done was significantly different between the two groups (mean for survivors, 67.9 ± 30.5 mL · kg-1 · min-1; mean for nonsurvivors, 100.7 ± 47.3 mL · kg-1 · min-1; p = 0.008). However flow did not contribute independently to the failure to survive but was related to regurgitation level, thus providing no further predictive value. With systemic AV valve regurgitation less than moderate survivors had a mean flow of 75.2 ± 30.2 mL · kg-1 · min-1, whereas nonsurvivors had a mean flow of 106.4 ± 57.0 mL · kg-1 · min-1 (p = 0.043). Patient resuscitation requiring chest compressions or open cardiac massage before ECMO and the levels of inotropic support were not significantly different between the survivors and nonsurvivors.
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Comment
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Extracorporeal membrane oxygenation is used for postoperative cardiac patients when ventricular dysfunction prevents adequate cardiac output. Reasons for ventricular dysfunction in the postoperative period leading to the need for ECMO include failure to wean from bypass, stunned myocardium, cardiac dysrhythmias, cardiac arrest, hypoxia, and pulmonary artery hypertension. The rationale for placing a patient on ECMO is to allow the myocardium to rest and recover function in order to maintain cardiac output without mechanical support. Patients were carefully considered for need to return to the operating room for additional surgery but no patients were found to be candidates because that would have offered no further benefit. If a patient survived at least 1 month after ECMO decannulation, the ECMO run fulfilled its purpose and these patients were considered cardiac survivors of ECMO. We chose to exclude patients who were removed from ECMO owing to brain death because it is uncertain whether the heart would have recovered.
Assessment of ventricular ejection fraction and severity of systemic AV valve regurgitation were evaluated by the cardiologist reading the echocardiogram at the time the study was performed. Thus echocardiogram reports were generated by physicians who were naturally masked as to patient outcome. Numerous sophisticated methods (Simpson’s, M-mode, and 2D formulas) to calculate and estimate ejection fraction using echocardiographic measurements were used at the discretion of the echocardiography reader at the time of the study. In some patients a visual estimation was made by experienced cardiologists. This method has been shown to correlate well with biplane contrast ventriculography as well as sophisticated echocardiographic methods of calculation [9]. The amount of systemic AV valve regurgitation was also a qualitative evaluation utilized among our expert echocardiography cardiologists. The proximal isovelocity surface area (PISA) technique was not used due to the retrospective nature of the study. In the majority of patients the amount of systemic AV valve regurgitation was not due to an anatomic abnormality of the valve. Instead we believe it was a reflection of ventricular dysfunction. In fact ejection fraction may have been overestimating the ventricular function in many instances where there was more severe regurgitation. That occurs because it requires less work for the ventricle to eject into the atrium than into the aorta. When this large volume regurgitates into the atrium, the ventricular ejection fraction will appear better than expected based on the actual cardiac output. The ventricle empties its volume but not in an effective direction.
Our retrospective investigation was concerned with the interpretation of information obtained by echocardiography as it relates to patient survival. The purpose of this study was not meant to be another analysis of numerous clinical variables on survival with the use of ECMO. Rather we investigated the usefulness of indicators of ventricular function by echocardiography, a commonly used diagnostic and monitoring method while patients remain on ECMO. We chose to analyze only a few variables surrounding the time of the echo as predictors for patient survival. None of the variables examined in detail correlated with patient survival except for patient sex and severity of systemic AV valve regurgitation.
In Table 1 it is readily seen that patients with more complex cardiac defects were less likely to survive. These patients are always a higher surgical risk from the start but it is impossible to predict who will survive. Thus the ability to provide additional information by echocardiographic variables to assist with determining prognosis in those who require ECMO postoperatively is a valuable tool.
We also evaluated the amount of preoperative AV valve regurgitation and its relationship to regurgitation during ECMO for all patients and for those with abnormal AV valve anatomy. There was no difference in preoperative regurgitation between survivors and nonsurvivors. In addition there was no significant effect of abnormal valve anatomy on survival or on the amount of AV valve regurgitation preoperatively or during ECMO. However there were only 8 patients with abnormal valve anatomy. With this small population it is difficult to accurately predict the true influence of valve anatomy on eventual survival.
Female sex is an interesting risk factor that was found to be significant for survival in our study. Likewise a recent report found that among children undergoing cardiac surgery female sex was associated with 51% higher odds of death than male sex but found no clear mechanism to explain this influence [10]. We also have no scientific explanation for this. Female patients did not have significantly more complex cardiac lesions. At this point we would not recommend counseling a family on their child’s prognosis based on sex. This finding suggests the need for further in-depth investigation.
The goal of this study was to evaluate ejection fraction and severity of systemic AV valve regurgitation seen on echocardiography while a patient was supported by ECMO as predictors of patient survival for 1 month after decannulation. We found that there was no significant difference in ejection fraction between survivors and nonsurvivors. Both had a mean ejection fraction of 41%. Ejection fraction is therefore not helpful in predicting survival while on ECMO. However the severity of systemic AV valve regurgitation was a strong predictor of patient survival, revealing that patients who had moderate to severe regurgitation were 16 times more likely to die (Fig 2).
We believe systemic AV valve regurgitation is a reflection of global ventricular function. When the ventricular function is failing it requires less energy to pump blood volume to a lower pressure cavity (the left atrium) rather than to the higher pressure systemic circulation. A significant volume of regurgitation can make ventricular function appear better than actual if ejection fraction is used as the indicator of function. The low likelihood of survival with the finding of moderate to severe systemic AV valve regurgitation while on ECMO should be an important factor when considering the need to list a patient for heart transplantation during their ECMO course.
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Fig 2. Severity of atrioventricular valve regurgitation in survivors versus nonsurvivors. A significantly higher percentage of nonsurvivors had at least moderate regurgitation (shaded area) and were 16.63 times more likely to die than patients with less than moderate regurgitation (white area; odds ratio = 16.63; p = 0.002).
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Study limitations
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The major limitation of this study is its retrospective design. Timing of the echocardiograms performed were not uniform between patients. We were unable to standardize the ECMO flow or other loading conditions. Therefore it was not possible to correlate the amount of AV valve regurgitation during ECMO at similar flow rates or volume status, or during an active weaning process for each patient. A prospective study with uniform scheduling of echocardiograms and dictation of variables to record and measure while patients are on ECMO would be more ideal. That would allow interpretation of echocardiograms at multiple times during the course of ECMO and evaluation of the relationship to survival.
There was also a small number of patients with abnormal systemic AV valves (all had endocardial cushion defects). The impact of abnormal valve anatomy on regurgitation and survival may be more significant when examining a larger number of patients who would require ECMO in this situation.
We did not separately evaluate the impact of the use of left atrial venting through septostomy or with a cannula. That may have a significant impact on survival and could be evidenced as well with decreased systemic AV valve regurgitation; it is currently the focus of another study at our institution.
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Conclusion
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With increasing confidence in ECMO and its use in the approach to surgery and postoperative care for increasingly complex congenital heart lesions, knowing the value of echocardiography variables can be helpful in directing a patient’s clinical course and assessing patient prognosis. We have found that estimated ejection fraction during ECMO is a poor measure of ventricular function and the likelihood for cardiac survival. Severity of systemic AV valve regurgitation while on ECMO is a more reliable predictor for 1-month survival after decannulation. We found the amount of regurgitation was unrelated to abnormal valve anatomy or preoperative valve regurgitation. Patients with less than moderate systemic AV valve regurgitation are 16 times more likely to survive than are patients with moderate to severe systemic AV valve regurgitation while on ECMO. Clinicians will need to combine previous knowledge of other prognostic indicators for cardiac ECMO survival with this new information.
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Acknowledgments
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This project was partially funded by the Mrs William Murphy Fund of the Riley Memorial Association.
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References
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Abstract
Introduction
