QT dispersion in athletic left ventricular hypertrophy

QT dispersion in athletic left ventricular hypertrophy Jamil Mayet, MD,a Prapa Kanagaratnam, MB,a Manjit Shahi, MD,a Roxy Senior, MD,c Michael Doherty, BSc,d Neil R. Poulter, FRCP,b Peter S. Sever, FRCP,b Clive E. Handler, FRCP,c Simon A. McG Thom, FRCP,b and Rodney A. Foale, FRCPa London, United Kingdom

Objective To assess whether physiologic left ventricular hypertrophy as a result of physical training is associated with an increased QT length or dispersion.

Methods Thirty-three subjects were assessed. These consisted of a group of international endurance athletes (including 8 rowers, 2 cyclists, and 1 triathlete), a group of 12 professional soccer players, and a further group of 10 control subjects. Each underwent 2-dimensional echocardiography and 12-lead electrocardiographic examination.

Results Left ventricular mass index was considerably greater in both the endurance athlete (163.3 ± 14.4 g/m2; P < .01) and soccer player groups (144.2 ± 5.5 g/m2; P < .05) compared with the controls (109.2 ± 6.3 g/m2). In spite of these large differences in cardiac structure there were no significant differences in QT parameters between the groups (QT dispersion 56.9 ± 5.5, 68.5 ± 9.5, and 67.2 ± 12.6 ms; QTc dispersion 61.4 ± 9.2, 69.4 ± 13.3, and 54.2 ± 6.5 ms; maximum QT 402 ± 10.3, 404 ± 9.6, and 392 ± 14.0 ms; and maximum QTc 404 ± 7.0, 413 ± 9.3, and 399 ± 9.9 ms among endurance athletes, soccer players, and controls, respectively).

Conclusion Left ventricular hypertrophy occurring as a consequence of athletic training does not appear to be associated with a major increase in QT length or QT dispersion. (Am Heart J 1999;137:678-81.)

The Framingham population study has identified left ventricular hypertrophy (LVH) as a powerful predictor of death.1 Subjects with LVH had a particularly high rate of sudden death, with an incidence of up to 10 times that of those without LVH.1 Apparently fit and healthy young athletes occasionally drop dead.2 In most cases postmortem examination reveals previously unexpected cardiac disease such as hypertrophic cardiomyopathy, but in a significant minority of such individuals no apparent cause is found, although physiologic LVH is often noted.3 Physiologic LVH is an adaptive increase in cardiac muscle in response to physical training. It is unclear whether this physiologic LVH is in some way implicated in the sudden deaths of some young athletes. A prolonged QT interval on the standard electrocardiogram (ECG) has been found to be associated with an increase in sudden death in patients with ischemic heart disease4 and also in apparently normal individuals.5 More recently, attention has been directed toward the interlead variations in QT segment length (dispersion). There is evidence that an increased QT dispersion on the ECG represents regional differences in myocardial From the aDepartment of Cardiology and bPeart-Rose Clinic, St. Mary’s Hospital; and the cDepartment of Cardiology and dBritish Olympic Medical Centre, Northwick Park Hospital. Submitted September 12, 1997; accepted June 26, 1998. Reprint requests: Jamil Mayet, MD, Department of Cardiology, St. Mary’s Hospital, Praed Street, Paddington, London W2 1NY, United Kingdom. Copyright © 1999 by Mosby, Inc. 0002-8703/99/$8.00 + 0 4/1/92714

recovery of excitability6 and this may lead to a more arrhythmogenic substrate.An increased QT dispersion is associated with increased risk in a variety of pathologic conditions: the long QT syndrome,7 congestive cardiac failure,8 hypertrophic cardiomyopathy,9 and postmyocardial infarction.10,11 An increased QT dispersion has recently been shown to be associated with LVH in hypertensive subjects.12-14 These studies provide strong evidence for a close link between these 2 parameters and it is tempting to speculate that QT dispersion is an important indicator of an arrhythmogenic link between LVH and sudden death. In this study we examined QT dispersion in subjects with physiologic LVH.

Methods Three groups of white, male subjects were studied: (1) 11 international endurance athletes who were very likely to have a high degree of LVH (this group was composed of 8 rowers, 2 cyclists, and 1 triathlete), (2) 12 professional soccer players, who were likely to exhibit a lesser degree of LVH than group 1, and (3) a control group of 10 medical students. No subject had a history of hypertension, diabetes mellitus, or alcohol abuse. No subjects were taking any form of medication. Each subject underwent 2-dimensional echocardiography and standard 12-lead ECG examination.The study was approved by the St. Mary’s Hospital Ethics Committee.

Echocardiography Two-dimensional echocardiographic studies were performed using a standard examination protocol.15 Left ventricular septal wall thickness, posterior wall thickness, and cavity size were

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Table I. Subject characteristics (mean ± SEM)

Age (y) Height (cm) Weight (kg) Body mass index (kg/m2) Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (beats/min)

Endurance athletes

Soccer players

Controls

26 ± 1.3 185 ± 2.4 84 ± 2.7 24.5 ± 0.34 121 ± 3.0 69 ± 1.6 63 ± 4.6

19 ± 0.3* 176 ± 2.1† 76 ± 1.6 24.6 ± 0.36 118 ± 3.7 68 ± 2.2 66 ± 4.3

20 ± 0.6* 178 ± 1.6 78 ± 2.7 24.8 ± 0.88 136 ± 5.8‡ 72 ± 3.2 68 ± 2.6

*P < .01 versus endurance athletes. †P < .05 versus endurance athletes. ‡P < .05 versus soccer players.

measured from the left ventricular short-axis view using 2dimensionally guided M-mode echocardiography. Particular attention was paid to obtaining a precise cross-sectional “onaxis” image of the left ventricle at the papillary muscle tip level. The papillary muscles were then bisected by the M-mode beam and simultaneous 2-dimensional and M-mode images obtained. Measurements of interventricular septum (IVS), posterior wall thickness (PWT), and left ventricular internal diameter (LVID) were made at end diastole using the Penn convention.16 Three consecutive cardiac cycles were measured and average values obtained. Left ventricular mass was calculated from Penn measurements using the cubed formula16: LV mass = 1.04 [(IVS + LVID + PWT)3 – (LVID)3] – 14 g. This figure was then adjusted for body surface area to give a value for LV mass index (LVMI). Blood pressures were measured at the end of the echocardiographic examination with the subject in a supine position.

ECG All 12-lead ECGs were performed at 25 mm/s with standard lead positions.Voltage height was measured from SV1 + RV5.17 QT intervals were measured on all possible leads by a single observer blinded to all clinical details using a digitizer. QT intervals were taken to be from the onset of the QRS complex to the end of the T wave, which was defined as its return to the TP baseline. If U waves were present, the QT interval was measured to the nadir of the curve between the T and U waves. QT intervals were corrected using Bazett’s formula18 to compensate for its known dependence on heart rate: QTc = QT/(RR)1/2 QTc dispersion was determined as the difference between the maximum and minimum QTc interval in different leads. No patient had less than 9 measurable leads.

Statistics All descriptive data are expressed as mean ± standard error of the mean (SEM).Analysis of variance was used to assess for differences between the groups. Simple linear regression analysis was used to assess correlations between variables.

Results Physical features of the three groups of subjects are presented in Table I. Endurance athletes were on average significantly older than soccer players and controls.

In addition they were taller and heavier, although body mass index was very similar among the 3 groups. Systolic blood pressure was lower in both sets of athletes compared with controls. Echocardiographic and ECG data are presented in Tables II and III, respectively. Both interventricular septal thickness and posterior wall thickness were greater among the endurance athletes compared with the soccer players, and these measurements were in turn greater among soccer players compared with controls. Although these differences were only statistically significant between the endurance athletes and the other 2 groups, LVMI was significantly greater in both the endurance athlete (163.3 ± 14.4 g/m2) and soccer player groups (144.2 ± 5.5 g/m2) compared with the controls (109.2 ± 6.3 g/m2). In spite of the large differences in cardiac structure there were no significant differences in QT parameters between the groups. There were no significant correlations between cardiac structural and QT measurements: LVMI versus maximum QTc, r = 0.11, P = .54; LVMI versus QTc dispersion, r = 0.17, P = .34. For interventricular septal thickness versus maximum QTc, r = –0.002, P = .99; interventricular septal thickness versus QTc dispersion, r = 0.11, P = .13.

Discussion LVH and QT parameters In this study, although there were large differences in LVMI between the groups, differences in maximum QT, maximum QTc, QT dispersion, and QTc dispersion were small and not statistically significant. However, on closer examination of the QT results both QTc dispersion and maximum QTc length are smallest in the control group, and it is possible that a much larger study might detect a small increase in these parameters in the athletes that may be statistically significant. Conversely, by assessing athletes with a very high degree of LVH (ie, rowers and cyclists) the chances of observing a difference in QT parameters, should they exist, ought to be enhanced and one might expect these differences to be most apparent

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Table II. Echocardiographic data (mean ± SEM) Endurance athletes Interventricular septal thickness (cm) Left ventricular internal diameter (cm) Posterior wall thickness (cm) LVMI (g/m2) *P †P

Soccer players

Controls

1.18 ± 0.06 5.64 ± 0.16 1.15 ± 0.05 163.3 ± 14.4

0.99 ± 0.04* 5.64 ± 0.08 1.08 ± 0.05 144.2 ± 5.5

0.89 ± 0.02* 5.40 ± 0.11 0.91 ± 0.05* 109.2 ± 6.3*†

Endurance athletes

Soccer players

Controls

402 ± 10.3 404 ± 7.0 56.9 ± 5.5 61.4 ± 9.2 37 ± 2.3

404 ± 9.6 413 ± 9.3 68.5 ± 9.5 69.4 ± 13.3 34 ± 2.7

392 ± 14.0 399 ± 9.9 67.2 ± 12.6 54.2 ± 6.5 32 ± 2.2

< .01 versus endurance athletes. < .05 versus soccer players.

Table III. ECG data (mean ± SEM)

Maximum QT (ms) Maximum QTc (ms) QT dispersion (ms) QTc dispersion (ms) ECG LVH (SV1 + RV5) (mV) No significant differences.

in the group with the greatest degree of LVH (ie, the endurance athletes). However, there was no trend linking QT parameters and LVMI among the groups, QTc dispersion and maximum QTc being greatest in the soccer players. The results of this study are compatible with a previous study comparing athletes with and without ventricular arrhythmias.19 The latter group had mean LVMI and QT dispersion measurements similar to the athletes in the present study.The group with ventricular arrhythmias had a considerably, and statistically significantly, greater mean QT dispersion although they had a similar mean LVMI. In addition, in a recent study of hypertensive subjects with LVH (mean LVMI 144g/m2), baseline mean QTc dispersion was 83 ms.12 However, after antihypertensive treatment, QTc dispersion fell to 63 ms and LVMI to 121 g/m2.Thus baseline LVMI among these hypertensive subjects (144g/m2) was very similar to that of the soccer players and less than the endurance athletes in the present study, although QTc dispersion was greater among the hypertensive subjects. In addition, the value of QTc dispersion after treatment and regression of LVH (63 ms) was closer to the values obtained in the 2 groups of athletes in the present study (69 ms and 61 ms, respectively).Therefore the results of these 2 studies taken together suggest significant dissociation between physiologic hypertrophy and abnormalities in QT dispersion. Maximum QTc length was not significantly different among the 3 groups, and the highest value for any group was 413 ms among the soccer players. In previous population studies QTc lengths of 420 to 440 ms and >440 ms have predicted increasing all-cause mortality compared with lower values.5,20 Therefore no group

had a maximum QTc that suggested a particularly high risk.The QT segment is composed of 2 parts: the QRS complex representing depolarization and the JT segment when repolarization occurs.To assess whether the similar QT segments in the 3 groups were masking differences in depolarization and repolarization, we measured the JT segments. However, these were also similar among the 3 groups.

How may hypertensive and physiologic LVH differ? The differences in hypertensive and physiologic LVH may be explained by microscopic myocardial changes in the hypertrophic process; in hypertensive subjects this consists of myocyte hypertrophy and an increase in the collagen interstitial matrix (ie, fibrous tissue).21 In contrast, LVH from athletic training is likely to be predominantly the result of myocyte hypertrophy with little, if any, increase in the interstitial matrix.This may explain why “athletic” LVH is not associated with diastolic dysfunction,22,23 in contrast to hypertensive LVH. It is also possible that differences in the coronary vascular reserve exist between the 2 types of hypertrophy. Coronary vascular reserve is certainly impaired in hypertensive hypertrophy,24 but whether this is the case in athletic hypertrophy is unclear. Either fibrosis or latent ischemia from impaired coronary vascular reserve could result in an increased QT dispersion if the changes in different parts of the ventricle are nonhomogeneous.These changes may conceivably result in re-entry circuits and ventricular arrhythmias. Other possibilities include neurohormonal differences that exist between subjects with pathologic and physiologic hypertrophy that may also affect ventricular repolarization.

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Limitations All the ECGs were recorded by a standard 12-lead machine.Therefore the leads were not all recorded simultaneously and this can affect both interlead QT length and R-R interval, particularly in young patients with a considerable degree of sinus arrhythmia. In view of this we have concentrated on QTc dispersion and QTc length to offer some compensation for the varying RR interval among the different leads.A further potential problem was the marked bradycardia observed in some subjects (mainly endurance athletes) inasmuch as Bazett’s adjustment18 is less reliable when the heart rate is very slow.There are 2 reasons to suppose that this was not a serious limitation. First, the soccer players were not excessively bradycardic and the results of that group and those of the endurance athletes were similar. Second, if the subjects with excessive bradycardia in the endurance group were removed from the analyses the results remained much the same. Perhaps the major potential problem of this study was the relatively small number of subjects studied, which raises the possibility of a type II error. However, the fact that there was no parallel trend between increasing QT parameters and increasing LVMI among the groups (in spite of the large differences in LVMI between them) limits the likely impact of any such error on the overall conclusion.

Conclusion LVH occurring as a consequence of athletic training does not appear to be associated with a major increase in QT length or QT dispersion. We thank the British Olympic Medical Centre for their cooperation. We also thank the staff of the Peart-Rose Clinic and the Cardiology Departments at St. Mary’s and Northwick Park Hospitals for their help with the study.

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