Relationship Between Type of Outflow Tract Repair and Postoperative Right Ventricular Diastolic Physiology in Tetralogy of Fallot
Implications for Long-term Outcome
Background Restrictive right ventricular (RV) physiology can be present early and late after tetralogy of Fallot repair. It is associated with a complicated early postoperative course but is favorable late after repair because it is associated with less pulmonary regurgitation, better exercise tolerance, and less QRS prolongation and symptomatic ventricular arrhythmias. It is not known, however, whether in the current surgical era, this physiology is present in tetralogy of Fallot patients at mid-term follow-up and whether it is related to the type of RV outflow tract repair. Finally, the impact of this physiology on the early evolution of QRS prolongation has not been examined previously. In this study we attempted to address these issues in a cohort of recently operated patients.
Methods and Results Ninety-five patients were studied 4.3 years after repair by Doppler echocardiography, serial electrocardiograms, and chest radiographs. Restrictive RV physiology defined by the presence of antegrade pulmonary artery flow in late diastole was present in 38% of the patients. It was more common in patients with transannular patch (TAP) repair compared with non-TAP repair (50% versus 21%, P<.05). QRS duration at follow-up was 121.2±17.6 and 132.6±11.8 ms in restrictive and nonrestrictive patients with TAP repair, respectively (P<.02).
Conclusions Restrictive RV physiology has been identified at mid-term follow-up in a contemporary surgical series. It is associated with less QRS prolongation, regardless of the technique used for outflow tract repair, and may be associated with fewer long-term complications. Nonrestrictive physiology is associated with the most marked QRS prolongation. This subgroup is most at risk from the late deleterious consequences of chronic pulmonary regurgitation.
The early results of tetralogy of Fallot repair are now excellent despite earlier surgical repair, and attention has turned to the issues of late morbidity and mortality.1 2 While the risk of surgery has fallen, the use of the transannular patch (TAP) has increased to >90% of neonates undergoing repair in recent series.3 The major concern with more radical right ventricular (RV) outflow tract reconstruction is the deleterious effects of pulmonary regurgitation on long-term outcome.4 5 6 7 8 Pulmonary regurgitation reduces exercise capacity4 5 6 7 and is associated with RV enlargement,7 8 late arrhythmias, and sudden death.9 Conversely, restrictive RV physiology, defined as antegrade pulmonary artery flow in late diastole,10 seems to protect against RV dilation in patients after repair of tetralogy of Fallot.11 We have recently reported a paradoxical effect of restrictive RV physiology in the early postoperative period and late after repair in these patients.11 12 13 In the early postoperative period, restrictive RV physiology was associated with a low cardiac output, effusions, and a prolonged postoperative course.12 Late after repair, the same Doppler echocardiographic features were associated with superior exercise performance,11 less ventricular dilation, and fewer arrhythmias.13 Indeed, we suggested a possible mechanoelectrical relationship on the basis of the observation of a linear relationship between RV size and QRS duration on the resting ECG, prolongation of which (>180 ms) was a highly sensitive predictor of symptomatic arrhythmia.13 The frequency of abnormal RV diastolic physiology and the determinants of this mechanoelectrical relationship are poorly understood.
The purpose of the present study was to assess restrictive RV physiology in a contemporary series of patients with tetralogy of Fallot repair, to relate this physiology to the technique used for outflow tract repair, and to determine its relationship to the evolution of QRS prolongation at mid-term follow-up.
Background clinical information was obtained from the patients' medical notes, including cardiac catheterization reports and surgical discharge summaries. Additional details on surgical procedures were obtained from surgeons' and perfusionists' notes.
From January 1, 1985, to December 31, 1994, 214 patients had surgical repair of tetralogy of Fallot at the Royal Brompton Hospital, London. This number does not include patients with associated absent pulmonary valve, double-outlet RV, or pulmonary atresia. We studied 95 of these patients by two-dimensional, M-mode, and Doppler echocardiography, ECG, and chest radiographs. Fourteen of the patients had participated in a previous study.12
Patients were unselected, other than being the respondents to a written invitation to attend for the study. The study protocol was approved by the hospital ethical committee, and informed consent was obtained from the patients or their parents.
In our institution, the preferred surgical protocol is a modified Blalock-Taussig shunt in cyanotic patients becoming symptomatic before 6 months of age, and primary repair between 6 and 18 months of age either electively or if symptomatic. Some of the patients were repaired at an older age or even as adults because of late referral from other countries. The transventricular approach was used in most of the patients (n=87). Outflow tract repair was carried out in four different ways: (1) muscular resection and/or pulmonary valvotomy (n=4), (2) outflow tract repair with a patch distal to the pulmonary valve (n=34), (3) transannular patch with a homograft monocusp to preserve pulmonary valve function (n=17), and (4) transannular patch without a monocusp (n=40).
Transthoracic echocardiography was performed with a 3.5- or 5.0-MHz transducer interfaced with a Hewlett-Packard Sonos 1500 Ultrasound System. After routine diagnostic imaging, an M-mode recording of the left ventricle (LV) was performed. RV end-diastolic area (RVEDA) from an apical four-chamber view was recorded to assess RV size.14 15 High-quality recordings for RV area measurements were obtained in 70 of 95 patients (74%). Spectral Doppler recordings were obtained from the pulmonary artery (PA), tricuspid valve (TV), and mitral valve (MV). The following methods and measurements were used: TV pulsed Doppler with sample volume at the level of the tips of the valve leaflets. E- and A-wave velocities and E-wave deceleration time were measured manually.12 Continuous-wave Doppler was used to interrogate tricuspid regurgitation for calculation of pressure differences between the RV and RA in systole. MV pulsed Doppler was performed with the sample volume at the tips of the valve leaflets, and parameters as for the TV were recorded. To assess the presence of restrictive RV physiology, PA pulsed Doppler recordings were obtained with the sample volume at the midpoint between pulmonary valve leaflets or their remnants and the bifurcation of the PA. This was defined by the presence of antegrade PA flow (A wave) in late diastole throughout inspiration and expiration.10 The velocity of the A wave and antegrade systolic flow were recorded. The duration of the pulmonary regurgitation signal was measured from the same Doppler tracing. No attempt was made to quantify the volume of the pulmonary regurgitation. Continuous-wave Doppler was used to assess residual RV outflow tract obstruction. If present, we defined significant residual outflow tract obstruction as a gradient of >40 mm Hg, and in our protocol such patients were excluded from the final analysis. Recordings were made with simultaneous ECG, phonocardiogram, and a respiratory tracing. Doppler recordings were made with minimal filtering and a paper speed of 100 cm/s. All patients were in sinus rhythm during the Doppler recordings.
TV Doppler was analyzed at peak inspiration and MV Doppler at end expiration. Pulmonary Doppler recordings were analyzed at both respiratory phases. LV M-mode and RVEDA were measured at end expiration as previously described.14 The mean of three measurements were analyzed. Of 95 patients studied, only 3 were excluded from the final analysis: 1 had residual outflow tract obstruction (>40 mm Hg), and in the other 2 patients, high-quality PA pulsed Doppler recordings could not be obtained because of thoracic deformities.
Resting 12-lead ECGs were recorded with the use of a standard Hewlett Packard system. QRS duration was defined as the distance between the first and last deflection from the isoelectric line, and the longest QRS duration in any lead was recorded. The mean rate of prolongation of the QRS complex was calculated by dividing the QRS difference from surgery to study by time of follow-up. This calculation was made in those with >1 year of follow-up.
Data are presented as mean (±SD) or median with range. Comparison between groups was by Student's t test or Mann-Whitney U test when appropriate. The normality of the data was assessed by Kolmogorov-Smirnov test. χ2 test or Fisher exact test was used to assess group differences for categorical variables. Multiple logistic regression with restrictive RV physiology as the dependent variable was undertaken to assess determinants for this physiology. Confidence intervals for the odds ratio were calculated as eB±1.96 SE. The null hypothesis was rejected when P<.05.
The anthropometric, preoperative, and surgical characteristics of the patients are detailed in Table 1⇓. There were few differences between the groups other than a significantly greater degree of preoperative pulmonary stenosis (P<.05) and a tendency to require a longer period of ventilatory support in the immediate postoperative period (P<.06) in the restrictive group.
Echocardiographic results are presented in Table 2⇓. Restrictive RV physiology was present in 36 patients (38%). In 20 other patients, antegrade PA flow in late diastole was present at inspiration only. These patients were included in the nonrestrictive group. The duration of pulmonary regurgitation normalized by dividing by the √RR interval was 10.7±2.1 and 12.1±2.1 in restrictive and nonrestrictive patients, respectively (P<.05). Restrictive RV physiology was significantly more common in patients with TAP (Figure⇓). TAP repair was the only significant independent variable when several possible predictors of RV restrictive physiology were assessed by multiple logistic regression analysis (Table 3⇓). The odds ratio (confidence intervals) for restriction in patients with TAP repair was 3.5 (1.2 to 8.5). QRS duration at follow-up is detailed in Table 4⇓. No differences in QRS duration were found 2 weeks after surgery between restrictive and nonrestrictive patients. At follow-up, QRS duration was 121.6±17.2 and 132.7±12 ms in restrictive and nonrestrictive patients with TAP repair, respectively (P<.02). There were no differences in duration of follow-up other than the outflow tract repair groups, where follow-up was 8.0±2.6 and 4.8±2.6 years in restrictive and nonrestrictive patients, respectively (P<.05). Cardiothoracic ratio (CTR) and RVEDA area did not differ between restrictive and nonrestrictive patients.
We have demonstrated restrictive RV physiology to be common in patients with repaired tetralogy of Fallot at mid-term follow-up. This physiology has also been reported as a temporary phenomenon in a similar percentage of patients early after repair as well as a much older cohort of patients late after repair.11 12 13 The results of the current study are similar to our earlier study of diastolic RV function in immediate postoperative patients, which showed that neither preoperative factors, age at surgery, nor cardiopulmonary bypass time were determinants for restrictive RV physiology.13 However, in our earlier study, there was no relationship between functional indices and the type of outflow tract reconstruction, although the numbers in each subgroup were small. In this study we examined a much larger cohort of patients, specifically to address whether the type of surgery influenced the manifestations and impact of RV diastolic dysfunction.
Restrictive RV Physiology in Primary and Secondary Repair
In the present study, there was a tendency (P=.1) toward a lower frequency of restrictive RV physiology after correction if a palliative shunt previously had been performed compared with the group undergoing primary repair. Likewise, in the study by Cullen et al,12 only 1 of 6 patients with a previous shunt had restrictive RV physiology compared with 8 of 15 with primary repair (P=.07). Our finding of similar numbers of TAP repair after palliation and primary repair (45% and 55%, NS) is interesting. Surgical series demonstrating the success of primary repair in infancy have a TAP rate in excess of 75% and up to 100% in one series.3 It is reasonable to assume, therefore, that some children have avoided TAP as a result of our policy. Whether this will prove to be beneficial remains to be seen.
Restrictive Physiology Versus Outflow Repair
Our finding of restrictive RV physiology in 50% of patients requiring TAP with or without a monocusp homograft valve is in agreement with our previous early postoperative study.13 However, restrictive RV physiology resolved in 13 of the 17 patients with restrictive physiology before discharge from the hospital. It is not yet known if early restriction predicts later restriction, and this must be addressed in the future.
At first sight, it would seem, paradoxically, that performing a TAP repair may be beneficial in that restrictive physiology that limits pulmonary regurgitation and improves exercise performance12 is more common in this group. It may be, however, that it is the outflow tract anatomy necessitating a TAP at the time of repair that is important. That is, there may be an anatomic and possibly hemodynamic substrate that predicts restriction. “Unnecessary” TAP or TAP in the absence of such a substrate (and hence the presence of nonrestrictive physiology) seems to be associated with the most rapidly progressive QRS prolongation, and we would predict this subgroup to be at greatest risk from the long-term adverse effects of free pulmonary regurgitation. The exact nature of the anatomic or hemodynamic substrate that predicts diastolic function is unknown. It is attractive to speculate, on the basis of our finding of restrictive physiology in all patients who have undergone complete repair of pulmonary atresia with intact septum,10 that it is related to an abnormal hypertrophic response with or without abnormalities in the arrangement of the myofibers in the right ventricle. Excessive fibrosis per se is unlikely to be the cause because although fibrosis in the RV wall increases with age, the occurrence of RV restrictive physiology early or late after operation is not related to age at repair.
If restrictive RV physiology could be predicted, then the surgical strategy could be selected accordingly. Our study cannot answer the question as to when to use TAP or when to avoid it. Clearly, TAP is indicated in patients with a severely hypoplastic outflow tract but we speculate that the high proportion of neonates undergoing correction with TAP reported in some surgical series may result in an excess of patients with the substrate for “free” pulmonary regurgitation and nonrestrictive physiology. It should not be forgotten, however, that both forms of RV diastolic physiology were seen with every type of outflow tract repair. Indeed, in our study of very long-term survivors (15 to 35 years), only 1 patient had TAP repair, but restrictive RV physiology was present in ≈50% of the 41 patients.11 However, the patients were older at repair and represented a naturally selected group of survivors. Multiple factors therefore seem to be associated with restrictive RV physiology, and while the functional implications of this physiology are becoming increasingly clear, its causes remain poorly understood.
Restrictive RV Physiology, QRS Duration, and Outflow Tract Repair
In our previous study of long-term survivors, prolongation of the QRS duration on the resting ECG of ≥180 ms was a sensitive marker for late arrhythmias and sudden death. Furthermore, there was a linear relationship between RV size and QRS duration, suggesting a mechanoelectrical interrelationship. It is well known that right bundle branch block is common after tetralogy of Fallot repair, and thus an increase in QRS duration after repair is expected. In the present study, there was no difference between any of the groups in the degree of QRS prolongation 2 weeks after surgery. The QRS duration progressively increased after surgery in all our patient groups. The greater degree of prolongation was seen in the nonrestrictive patients with TAP, being significantly greater than in those undergoing the same type of outflow tract repair but with restrictive physiology.
On the basis of our previous demonstration of mechanoelectrical interaction, we suggest that our findings reflect a greater degree of pulmonary regurgitation and rate of RV dilation in nonrestrictive patients. Conversely, as restrictive RV physiology reduces pulmonary regurgitation, QRS duration was shorter in patients with this physiology. In the present study, CTR and RVEDA were not significantly increased in the nonrestrictive patients. Given the short follow-up period and methodological difficulties in assessing RV size, this it not surprising.15 It is also of note that when a TAP repair with a monocusp valve was used, no increased QRS prolongation occurred in nonrestrictive patients. The present study was not designed to compare monocusp with TAP repair without a monocusp; however, at mid-term follow-up, patients with a monocusp appear to have less QRS prolongation and no residual pulmonary stenosis. A monocusp, therefore, may preserve early RV function, although the long-term utility of monocusp homografts is uncertain.
Limitations of the Study
The median follow-up in the present study was only 4.3 years, but this was necessary to evaluate the effects of contemporary surgical techniques. Nonetheless, only a relatively small number of patients had transatrial/transpulmonary repair. This approach is becoming increasingly popular, but because of our limited data, no further conclusions can be drawn. No matter what the surgical approach, our protocol does not allow analysis of the effects of complete primary repair in early infancy. This is because our current and continuing policy precludes these patients from primary repair. A similar detailed mid-term analysis of mid-term functional outcome is required to substantiate some of the inferences of this study. Finally, when discussing the potential long-term effects of restrictive or nonrestrictive RV physiology, data are available only in patients operated on in a different era; the underlying physiology is identical, however, and our data are consistent with our current understanding of the hemodynamic consequences. Long-term follow-up will be required, but we believe our conclusions regarding the long-term detrimental effects of chronic RV volume overload to be valid.
The clinical importance of this study is the demonstration of restrictive RV physiology in a substantial number of patients who have undergone TAP repair and, conversely, the most marked prolongation of QRS duration in those with TAP but nonrestrictive physiology. Surgical strategies that minimize the need for transannular patching would seem to confer more advantage than the putative benefits of primary repair in early infancy, with its almost invariable need for more aggressive outflow tract reconstruction. No matter what the type of repair, however, nonrestrictive physiology with progressive RV dilation can occur, and because of its potential implications for serious or life-threatening late arrhythmias, the QRS prolongation in these patients must be followed in longitudinal studies. It is likely that differences observed between these different groups of patients will increase with longer follow-up.
Dr Norga˚rd was supported by grants from Unger Vetlesen Medical Fund and the Norwegian Research Council.
- Received April 8, 1996.
- Revision received July 1, 1996.
- Accepted July 16, 1996.
- Copyright © 1996 by American Heart Association
Carvalho JS, Shinebourne EA, Busst C, Redington AN. Exercise capacity after complete repair of tetralogy of Fallot: deleterious effects of residual pulmonary regurgitation. Br Heart J. 1992;67:470-473.
Norga˚rd G, Bjørkhaug A, Vik-Mo H. Effects of impaired lung function and pulmonary regurgitation on maximal exercise capacity in repaired tetralogy of Fallot. Eur Heart J. 1992;13:1380-1386.
Redington AN, Oldershaw PJ, Shinebourne EA, Rigby ML. A new technique for the assessment of pulmonary regurgitation and its application to the assessment of right ventricular function before and after repair of tetralogy of Fallot. Br Heart J. 1988;60:57-65.
Redington AN, Penny D, Rigby ML, Hayes A. Antegrade diastolic pulmonary artery flow as a marker of right ventricular restriction after complete repair of pulmonary atresia with intact ventricular septum and critical pulmonary valve stenosis. Cardiol Young. 1992;2:382-386.
Gatzoulis MA, Clark AL, Cullen S, Newman CGH, Redington AN. Right ventricular diastolic function 15 to 35 years after repair of tetralogy of Fallot: restrictive physiology predicts superior exercise performance. Circulation. 1995;91:1775-1781.
Cullen S, Shore D, Redington AN. Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot: restrictive physiology predicts slow postoperative recovery. Circulation. 1995;91:1782-1789.
Gatzoulis MA, Till JA, Somerville J, Redington AN. Mechanoelectrical interaction in tetralogy of Fallot: QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death. Circulation. 1995;92:231-237.