Results

The results are shown in table 1.

Mean sNN50 was reduced in patients with tetralogy of Fallot when compared with age matched normal controls (fig 1). The range of values was wider in patients with tetralogy of Fallot. Heart rate variability was less than the normal range in 12 (43%) of the patients with tetralogy of Fallot.

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Figure 1

Heart rate variability following repair of tetralogy of Fallot plotted on a logarithmic scale against the range of values for normal controls aged 12–34 years. Mean sNN50 in patients with tetralogy of Fallot was significantly reduced compared with the age matched normal controls (p < 0.05). Heart rate variability was below the normal range in 12 of the patients with repair of tetralogy of Fallot.

Discussion

Asymptomatic ventricular arrhythmias are common after repair of tetralogy of Fallot. Premature ventricular beats can be detected on Holter monitoring in around 45% of patients.17 Risk factors for asymptomatic ventricular arrhythmias include older age at repair,18 ,19 increasing time since surgery,20 increased right ventricular pressures, and poor ventricular function.21 ,22 The significance of asymptomatic ventricular arrhythmias is not clear. Although ventricular arrhythmias are a risk factor for sudden death following repair of tetralogy of Fallot,23 ventricular arrhythmias are common whereas sudden death is comparatively rare. At present there is no good way of identifying individuals at high risk of sudden death.

The autonomic nervous system has an important influence on myocardial stability.24 Sympathetic activation25 and parasympathetic impairment26 reduce the threshold for ventricular arrhythmias. Autonomic function may be measured by various techniques.27 ,28 Cardiovascular reflex testing measures heart rate and blood pressure responses to various manoeuvres, including Valsalva, tilting, and drugs, but a major problem is that it suffers from lack of standardisation and is difficult to interpret.29 An alternative and more reliable method of assessing cardiac autonomic function is to measure heart rate variability. Different indices of heart rate variability reflect parasympathetic and sympathetic activity.30 Heart rate variability can be measured by either frequency or time domain techniques but domain parameters have mainly been used to correlate reduced heart rate variability with impaired left ventricular function.11 ,26 The sNN50 is a count of the total number of differences between adjacent RR intervals that are longer than 50 ms in a 24 hour electrocardiographic recording, and provides an index of parasympathetic function.7

Although reduced heart rate variability has been associated with impaired left ventricular function, the relation between heart rate variability and right ventricular function has not previously been explored. One of the problems in evaluating this relation is that the geometry and trabeculation of the right ventricle make it difficult to measure its function accurately.31 In our study, we chose to measure right ventricular function by radionuclide using first transit studies, as this is a relatively reproducible and non-invasive technique,32 and has been used previously to evaluate right ventricular function in patients with chronic lung disease33 and tetralogy of Fallot.34

Our study shows that reduced heart rate variability may be found in patients 10 years or more after repair of tetralogy of Fallot. Unlike previous studies in patients with ischaemic heart disease, reduced heart rate variability following repair of the tetralogy is not related to impaired left ventricular function. Instead it is associated with increasing age and indices of impaired right ventricular haemodynamics, including increased right ventricular dimension, increased right ventricular pressure, and, to a lesser extent, right ventricular ejection fraction, as measured by radionuclide scan. The association of reduced heart rate variability with impaired right ventricular haemodynamics suggests the former might be useful as a simple non-invasive indicator of deteriorating right ventricular function in patients with tetralogy of Fallot. This could be helpful—for example, when trying to determine the timing of valve replacement in patients with free pulmonary regurgitation.

Gatzoulis et al described the measurement of QRS and QT duration as well as JT, QRS, and QT dispersion as a method of identifying patients at risk of ventricular arrhythmias and sudden death late following repair of tetralogy of Fallot.4 ,34When these measurements were applied to our cohort of 28 patients we found that all had at least one increased value, implying an increased risk of ventricular arrhythmia, but only one of our patients had a ventricular arrhythmia (ventricular premature beats) on Holter monitoring. None of the others had either documented ventricular arrhythmias or symptoms of arrhythmias. A major problem with measuring QT and JT interval and dispersion in these patients is the difficulty in determining the end of the T wave and discriminating a T wave from a U wave. Of all the measurements from the surface ECG, Gatzouliset al found that the best predictor of sudden death was a QRS duration of > 180 ms. In our study, prolonged QRS was the only electrocardiographic finding associated with reduced heart rate variability. In addition we found a positive correlation between right ventricular end diastolic dimension on echocardiography and QRS duration, as well as between increased right ventricular pressure and QRS duration. A similar relation was described by Gatzoulis et al, who found a strong correlation between QRS duration and cardiothoracic ratio in patients with repaired tetralogy of Fallot. They suggested that increased QRS may only be a surrogate’ risk factor for sudden death in that if the right ventricle is dilated and develops tachycardia, the patient is more likely to become haemodynamically compromised and die. However, the finding that a dilated right ventricle and increased right ventricular pressures are also associated with reduced heart rate variability suggests that impaired right ventricular function in itself might be responsible for electrical abnormalities. The present findings represent the first report of such a relation.

Whereas only a prospective study would show whether reduced heart rate variability is an independent risk factor for late sudden death in patients after repair of tetralogy of Fallot, its association with other known risk factors for sudden death—including increasing age, a dilated right heart, raised right heart pressures, and wide QRS on surface ECG—indicate that autonomic dysfunction may play an important role in myocardial instability in these patients.

Heart rate variability is extremely easy to measure on a 24 hour ECG using commercially available software. Many patients will undergo 24 Holter monitoring after repair of tetralogy of Fallot as part of routine follow up investigations, and it adds little extra time to do heart rate variability analysis. Low heart rate variability may alert the clinician to problems of impaired right ventricular function and the possibility of increased risk of serious arrhythmias, and suggest the need for more vigilant follow up.