Asian Cardiovasc Thorac Ann 2006;14:279-283
© 2006 Asia Publishing EXchange Ltd
Restrictive Physiology in Tetralogy of Fallot: Exercise and Arrhythmogenesis
Kaushalendra S Rathore, MCh,
Surendra K Agrawal, MCh,
Aditya Kapoor, DM
Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
For reprint information contact: Kaushalendra S Rathore, MCh Tel: 61 2 4314 57784 Fax: 61 2 9588 4129 Email: kaushalendra_rathore{at}hotmail.com, Suite 15, Level 4, St. George Hospital, Sydney, NSW 2217, Australia.
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ABSTRACT
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The effect of right ventricular restrictive physiology on exercise capacity and arrhythmogenesis after correction of tetralogy of Fallot was assessed in 80 patients aged 7.9 ± 3.6 years. Right ventricular restrictive physiology was defined as the presence of an A wave across the pulmonary artery on 2-dimensional echocardiography. At the 6 month follow-up, 52 patients had restrictive physiology (group 1). A transannular patch was used in 36 patients in group 1 (62%) and in 19 (86%) of the 28 patients without restrictive physiology (group 2). Maximum heart rate attained (69% vs. 77%), maximum predicted heart rate (211 ± 12.6 vs. 226 ± 24.2 beats·min–1), and metabolic equivalents (7.6 ± 3.2 vs. 8.1 ± 2.6) were higher in group 2, but not significantly. The chronotropic index was similar in both groups. In group 1, 14% of patients presented with ventricular premature complexes at 6 months. No effect on exercise capacity and arrhythmogenesis could be attributed to restrictive physiology, but both groups had chronotropic incompetence compared to normal children.
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INTRODUCTION
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In patients with tetralogy of Fallot (TOF), total correction at an early age is now the accepted management, with optimal results. Even after total correction, a substantial number of patients exhibit right ventricular (RV) restrictive physiology (diastolic dysfunction).1 The incidence of restrictive physiology varies from 50%–70%.2 The etiology has not been established but its negative impact on morbidity and mortality in the immediate postoperative period is well documented.1 Previous studies have shown these abnormalities to be transient, often resolving within a few weeks.1–3 We conducted a prospective study to determine the natural course of RV restrictive physiology and its effects on exercise capacity and arrhythmogenesis in patients undergoing total correction of TOF.
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PATIENTS AND METHODS
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From January 2001 to June 2003, 80 patients undergoing total correction of TOF in our institute were assessed prospectively. They included patients with or without a transannular patch, and those with previous surgery for a modified Blalock-Taussig shunt. Exclusion criteria were re-operations, the use of extracardiac conduits, and permanent pacemaker insertion; 2 patients with a pacemaker were excluded. Total correction was undertaken using standard aortic-bicaval cannulation and moderate hypothermia. The ventricular septal defect (VSD) was closed through the right atrium using a Dacron patch with continuous polypropylene sutures. Transannular patching and augmentation of the main pulmonary artery (PA) and right and/or left PA was performed with an autologous untreated pericardial patch during rewarming without aortic crossclamping on a beating perfused heart. Venting was carried out through the patent or created foramen ovale.
Restrictive physiology was defined as the presence of laminar antegrade diastolic PA flow throughout the respiratory cycle, which was coincident with atrial systole. The patients were divided into 2 groups based on the presence (group 1) or absence (group 2) of laminar antegrade diastolic PA flow. Transthoracic 2-dimensional echocardiography was performed at the time of discharge and at the 3 and 6 month follow-up examinations. A Hewlett-Packard Sonos 5500 (Hewlett Packard, Inc., Anaheim, CA, USA) with a 5 or 7.5 MHz transducer was used for M-mode imaging of the left and right ventricular cavities. This was followed by detailed pulsed Doppler echocardiography: transtricuspid and transmitral valve characteristics at the level of the tips of the valve leaflets, in apical 4 chamber view; superior venacaval Doppler profile, 1–2 cm proximal to the right atrium; and PA systolic and diastolic Doppler flow. The peak velocity, integral, and duration of antegrade systolic and diastolic PA flow, and duration of pulmonary regurgitation were measured. While recording transtricuspid and transmitral flow, the respective E and A wave velocities, velocity-time integrals, deceleration times, and durations were recorded in each case.
Diagnostic catheterization to determine the anatomy was performed in all patients, according to our institutional protocol. The Nakata index was calculated as the pre-branching diameter of the right and left PA divided by the diameter of the aorta at the level of the diaphragm. The Z-value was taken from standard charts, depending on weight and body surface area. Treadmill exercise tests were carried out using the standard Bruce protocols at the 6 month follow-up. An abnormal response was documented if there was ST-T wave depression or elevation of 1 mm for 60 msec. The exercise was stopped on exhaustion of the patient. The recovery phase after exercise was 3 minutes, during which any rhythm changes were recorded. The data collected were exercise time, maximum heart rate attained, maximum predicted heart rate, percentage of predicted heart rate, and metabolic equivalents (METs) achieved. Predicted peak oxygen uptake (VO2) was calculated from the Astrand and Wasserman equations.4,5 Chronotropic index, the ratio of heart rate reserve used to metabolic reserve used at peak exercise, was taken as an indicator of the heart rate response to exercise.6 Continuous ambulatory 24 hr Holter recordings were carried out to detect any arrhythmias at 6 months postoperatively. Ventricular arrhythmias were graded using Deanfield’s modification of Lown’s criteria.7,8
Statistical analysis was performed with SPSS version 10 software (SPSS, Inc., Chicago, IL, USA). Continuous variables were calculated as mean ± standard deviation or median and range, where appropriate. Significance was determined at a p value of < 0.05. All p-values are two-sided, and confidence intervals are 95%.
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RESULTS
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The demographic profile is shown in Table 1
. The patients’ ages ranged from 4 to 27 years (mean, 7.9 ± 3.6 years). The duration of follow-up was 6 to 39 months (mean, 22.4 ± 3.5 months) and no patient died or was lost to follow-up in this period. Males predominated: 64/80 (80%). Restrictive physiology was found in 65%. Both groups were matched in terms of age, sex, weight, and symptoms at surgery, history of previous surgery, PA size, and hematological data. All patients were discharged from the hospital on medications including digoxin and furosemide. A transannular patch was used in 55 (69%) patients, and there was no statistical difference between the two groups: 36/52 (70%) in group 1; 19/28 (68%) in group 2.
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Table 1. Profile of 52 (Group 1) Patients with Restrictive Physiology and 28 (Group 2) without Restrictive Physiology at 6-month Follow-up
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Echocardiography in the immediate perioperative period showed that an A wave was present in 58/80 patients (72.5%) and absent in 22 (27.5%). At the 6 month follow-up, 6 patients had lost this restrictive feature. The flow integral increased significantly during inspiration compared to expiration (Table 2). The PA A wave velocity also showed marked inspiratory augmentation, and the A wave duration increased on expiration compared to inspiration. Mild to moderate pulmonary regurgitation was noted in 43 patients in group 1 immediately postoperatively: mild in 30 (52%), moderate in 13 (22%); and in 14 patients in group 2: mild in 11 (50%), moderate in 3 (14%); p > 0.05. Pulmonary regurgitation showed a significant decrease over time in group 1 (at 6 months: mild in 10, 19%; moderate in 6, 12%). However, the severity of pulmonary regurgitation remained the same in group 2 at 6 months. Patients with RV restrictive physiology had reversal of superior vena caval flow during atrial systole (Table 2).
All E-wave variables were reduced in group 1, while A wave variables became predominant (Table 3). This made the E/A ratio lower in group 1. There were no statistical differences in other variables between groups. Mild tricuspid regurgitation was present at 6 months in 30 (58%) patients in group 1 and 13 (46%) in group 2. All of the patients had normal dimensions and contractility of the left and right ventricles at their last follow-up.
Children under 4 years of age were not included in the treadmill test. Another 3 patients were unable to perform a moderate level of exercise (85% of age-predicted maximum exercise) because they could not understand the exercise protocol. Grade 1 ventricular premature complexes were seen in 4 patients in group 1 and 5 in group 2. Maximum exercise times were comparable in both groups (Table 4). Eleven patients in group 1 and 5 in group 2 exhibited an age-predicted heart rate < 85%. Maximum heart rate attained and maximum predicted heart rate were both higher in group 2, but not statistically different. The METs achieved by the patients in group 2 were higher than those in group 2, but not significantly different. The calculated predicted VO2 values were also similar in both groups. Chronotropic index ranged from 40% to 97% in group 1, and from 44% to 96% in group 2. The mean chronotropic index was similar in both groups, but it was significantly lower than in normal peers. There was no correlation between the presence or degree of pulmonary regurgitation and its effect on exercise capacity in either group. In all patients, the test was terminated because of fatigue.
The most common electrocardiographic changes observed were right bundle branch block in 19 (24%) patients and 1st degree atrioventricular block in 3 (4%). The 24 hr Holter monitoring revealed 2 more patients with grade 1 ventricular premature complexes (total, 11; 14%). Both of these patients were in group 1. Sustained ventricular tachycardia or sudden cardiac death did not occur in any patient during follow-up.
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DISCUSSION
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Right ventricular diastolic dysfunction exists in a significant number of patients undergoing TOF repair. It occurs when RV end-diastolic pressure exceeds PA diastolic pressure. The reduction in RV diastolic compliance is reflected as antegrade diastolic flow in the PA during atrial systole and by retrograde flow through the superior vena cava.1 Due to this restriction at end-diastole, the right ventricle acts merely as a passive conduit between the systemic venous inflow and PA inflow during atrial systole. Gatzoulis and colleagues2 observed these findings to be transient, as they resolved within a few weeks. In our study, this phenomenon of RV restriction was seen in 72.5% of patients, a higher incidence than previously reported.3 This could be a reflection of the older age of our patients at the time of surgery. However, a marginal reduction in restrictive features was seen at the 6 month follow-up. It will be interesting to observe these patients for a longer period to see if there is any correlation with the occurrence of ventricular arrhythmias or sudden cardiac death.
Peak oxygen uptake is determined by cardiac output and the arterial venous oxygen difference, age, sex, muscle mass, genetic endowment, lung function, and efficacy of exercise.4 Most patients in this study had a lower than predicted peak VO2 than those in other studies.9 Carvalho and colleagues10 have shown a high mortality rate in patients with VO2 < 14 mL·kg–1·min–1. Any reduction in peak VO2 coincides with a reduction in ventilation capacity. Tokumura and colleagues9 subjected their patients to a brief strenuous exercise protocol to demonstrate the acute cardiopulmonary response, rather than gradual exercise as in our study. The age-predicted heart rate response and VO2 were not significantly different in the 2 groups in our study; however, a delayed decrease of these parameters after exercise was observed in most patients. This could be explained by the fact that they exhibited mild to moderate chronotropic incompetence at the time of follow-up. Chronotropic incompetence and a low chronotropic index have been shown to be associated with adverse outcomes in these patients.6 Most patients in our study had an age-predicted maximum heart rate > 85%. Sex-based analysis was not undertaken because of the smaller numbers of females in both groups.
Mulla and colleagues11 reported that aerobic capacity is limited by RV dysfunction and not by use of a transannular patch, chronotropic impairment, or restrictive pulmonary function. However, this was contradicted by Mahle and colleagues12 who demonstrated no association between age at total correction, aerobic capacity, peak work rate, or pulmonary function. A trend towards delayed response of the heart rate to exercise was seen; these patients had a small increase in heart rate in the first 5 to 6 min, thereafter a steep rise in heart rate was noticed between 7 to 9 min. During recovery, a decrease in heart rate occurred gradually. After 6 min, less than one third of METs were achieved by most patients, and in the latter half of the exercise, the remaining two thirds of METs were achieved. These findings show an inappropriate response to exercise, reflecting chronotropic incompetence.
Unnoticed ventricular arrhythmias are common after total correction of TOF. Holter monitoring detected ventricular premature complexes in 45% of patients.13 These changes are known to occur more often with increased age, impaired RV function, and widening of the QRS complex.13 Ventricular arrhythmias are an important cause of sudden cardiac death in these patients. There were 11 patients (14%) in this study with grade 1 ventricular premature complexes. Sustained ventricular tachycardia was not detected in any patient where a transatrial approach was used, but it is well known after transventricular repair of TOF. McLeod and colleagues13 stressed that reduced heart rate invariably follows repair of TOF, especially if the patient has impaired RV function. Thus, restrictive physiology should increase the chances of ventricular arrhythmias and sudden cardiac death. A wide variation exists in the ability of patients to tolerate pulmonary regurgitation without development of late RV dilatation.14 The incidence of RV dilatation is higher in patients who had a transannular patch.15 This makes the right ventricle more susceptible to gradual dilatation, as observed by Yetman and colleagues16 who operated on patients during infancy and found more RV dilatation and dysfunction secondary to chronic pulmonary regurgitation. Similarly, Singh and colleagues17 stated that correction in infancy might not prevent late RV diastolic dysfunction if chronic pulmonary regurgitation results from RV outflow tract reconstruction. Carvalho and colleagues10 have shown that restrictive physiology reduces pulmonary regurgitation. They also documented improvement in pulmonary regurgitation due to RV restriction, leading to better physical activity of the patients. The preventive role of RV restriction on pulmonary regurgitation was seen in this study where it was noted in a substantial number of patients at medium-term follow-up, but RV restriction had no impact on exercise capacity and arrhythmogenesis.
A limitation of this study is that quantitative analysis of the right ventricle is not possible with transthoracic 2-dimensional echocardiography. Other noninvasive methods such as magnetic resonance imaging and 3-dimensional echocardiography could be used. Reproducibility is operator-dependent. Exercise performance and chronotropic index is dependent on the motivation of the patients. A few patients were unable to understand the exercise protocol, so the results were suboptimal. RV dilatation and pulmonary regurgitation appear in the clinical arena on long-term follow-up. The follow-up duration in our study was 39 months. Longer follow-up will be necessary before definitive conclusions can be drawn.
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REFERENCES
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ABSTRACT
INTRODUCTION
