In this study, the effect of methylphenidate on the cardiovascular functioning of children with ADHD was examined by looking at systolic and diastolic BP, HR, QT, JT, QTc, JTc, QTd and JTd.
QT represents the interval from the beginning of the Q wave to the end of the T wave, and therefore corresponds to ventricular depolarisation and repolarisation. Similarly, JT represents the interval from the J point, which signifies the end of ventricular depolarisation, to the end of the T wave, and therefore corresponds to ventricular repolarisation. QT and JT intervals are, however, dependant on HR and are therefore corrected in order to compensate for individual differences in HR. Therefore, QTc and JTc are analysed in order to determine whether ventricular abnormalities are present.
QTc is commonly used as a measure of the depolarisation and repolarisation of the ventricles of the heart and is thus a surrogate marker for the risk of adverse cardiac events, and in severe cases, sudden death.9
A prolonged QTc interval, indicative of a prolonged cardiac repolarisation, has indeed been associated with cardiac arrhythmias9
and an increased risk of morbidity and mortality.19
However, a more generally accepted absolute index of cardiac repolarisation, which is believed to be depolarisation independent, is the HR-corrected JT interval, i.e. the JTc interval.
Formulas used to correct QT and JT intervals include linear, logarithmic, square-root and exponential equations.19
Correction methods such as Bazett’s formula,15
and Rautaharju algorithms20
are commonly used. However, no universally accepted method exists. Bazett’s formula is believed to work well with heart rates between 50 and 90 bpm, but over-corrects at low heart rates and under-corrects at high heart rates.14
Fridericia’s formula, on the other hand, under-corrects at low heart rates and over-corrects at high hearts rates, such that the over-correction at high heart rates may lead to QTc values which are artificially low.14
A study by Wernicke et al.14
has, however, indicated that QT correction methods developed specifically for adults do not apply to children, since it is known that QT intervals increase with age. A meta-analysis involving 2 288 children and adolescents with ADHD14
found the most appropriate QT correction formula for children and adolescents to be
where RR represents the length of the entire cardiac cycle in seconds. This data-derived method is based on linear regression techniques where the optimum correction factor determined was that value which resulted in zero correlation between the QTc and RR values.14
Another value commonly used in the assessment of cardiac functioning is QT dispersion (QTd), which is a measure of interlead variations in QT interval lengths of the surface 12-lead ECG.21
QTd is therefore a non-invasive marker of underlying inhomogeneity of myocardial repolarisation.22
An increased QTd reflects cardiac instability and an increased risk for cardiac arrhythmias.21
Increased QTd values have been found in cardiac disorders such as the long-QT syndrome, drug toxicity and dilated and hypertrophic cardiomyopathies.23
Interestingly, Glancy et al.24
discovered that an increase in QTd values, measured four weeks after a myocardial infarction, was associated with an increased rate of mortality in the next five years. Similarly, JT dispersion is a measure of inter-lead variations in JT interval lengths of the surface 12-lead ECG and is also commonly used to detect repolarisation abnormalities and cardiac instability.25
The BP results from this study support the findings by Biederman et al.
Wernicke et al.
and Ballard et al.
which indicated that stimulant usage is associated with increases in both systolic and diastolic blood pressure. These findings therefore confirm the sympathomimetic properties of stimulants commonly used to treat ADHD.
The ECG results from this study support previous findings by Ballard et al.
and Spencer et al.
which indicated that methylphenidate usage is associated with an increase in HR. The shortening of the QT and JT intervals is expected due to the increase in HR caused by methylphenidate usage. However, it would appear that methylphenidate does not adversely affect QTc and JTc values or dispersion values. These results therefore support the previous findings by Ballard et al.5
and Spencer et al.
which indicated that methylphenidate does not affect ECG parameters.