This study, for the first time, shows the evolution of the resting ECG and SA-ECG characteristics and of the HV interval in non-selected adult MD patients monitored every year in the same reference centre. Some significant modifications of resting ECG were observed in four patients and abnormal SA-ECG in six patients, and were strongly associated with an HV interval prolongation. The HV interval increase was not linked to any new symptoms such as syncope or palpitations, or to the duration of the follow-up.
Nguyen et al20
reported that abnormalities of the cardiac conduction system were commonly observed in MD due to frequent fatty infiltration and fibrosis of the His bundle. The electrophysiological consequences of these histopathological lesions were frequent infrahissian conduction disturbances on electrophysiological testing (prolonged HV interval) and a high risk of complete AVB in MD patients.12 13 21
In animal models for dystrophy myotonic protein kinase (DMPK) reduction the same histopathological lesions and His Purkinje system alterations were reported.22
A time-dependent degenerative process has been suggested by Groh et al
who observed a correlation between age and ECG abnormalities, and by Prystowsky et al
who in serial electrophysiological studies demonstrated the progression of infrahissian conduction time in a small number (n=9) of non-consecutive MD patients. However, in the large study by Laurent et al
including 51 MD patients with a normal HV interval of less than 70 ms followed up during 57±36 months, only one patient developed a complete AVB, 52 months after the initial electrophysiological testing, whereas 19 of 49 patients with HV interval of 70 ms or greater developed 3° AVB. These results suggest two categories of adult MD patients: one characterised by early infrahissian conduction disturbances (HV interval ≥70 ms) frequently risking complete AVB, and a second category of adult MD patients who may exhibit a very slow progression of infrahissian conduction time. This hypothesis is consistent with our results, which through serial electrophysiological testing demonstrated a progression of HV interval in only five of 25 patients during a prolonged period of 90 months as opposed to Prystowsky et al
who reported an aggravation of HV interval in seven of nine selected patients during a short 3-year period. This difference can be explained by the high rate of abnormal resting ECG (7/9) and prolonged HV interval (3/9) at the initial evaluation in the Prystowsky study.14
Second, the high prevalence of complete AVB documented in memory pacemaker in MD patients with an early HV interval of 70 ms or greater points to a severe evolution of the infrahissian conduction time in this subgroup of patients.12 13
This heterogeneity of MD patients in terms of infrahissian characteristics is compatible with the heterogeneity of the size of the mutation in the different organs (somatic mosaicism), which is not exactly the same for leucocytes. No correlation has been established between respiratory insufficiency, weakness, or cardiac disease, probably because the effect of the non-translated CTG repeat expansion is not unique but multiple24
and is not uniform from one patient to another.
A second major finding of our study is the strong relationship between the evolution of cardiac conduction disturbances on resting ECG and the increase in the HV interval in a serial study. No correlation between resting ECG and HV interval or histopathological lesions12 14 15 20
has been reported in the literature, but the previous studies did not integrate the dynamism of the atrioventricular conduction parameters in their analysis. In our study patients with a significant increase in the HV interval corresponded approximately to those with a significant progression of cardiac conduction abnormalities on resting ECG. Mörner et al25
pointed out the importance of analysing the progression of the atrioventricular conduction disturbances on ECG. A progressive increase in PR interval and QRS duration on resting ECG has been demonstrated as being statistically associated with higher mortality in MD patients.10 25
Groh et al5
showed in a large population of MD patients that the resting ECG was a crucial key in defining those patients at high risk of sudden death. In the subgroup of patients at high risk of sudden death in accordance with the Groh criteria, Laurent et al13
showed that the implantation of a prophylactic pacemaker in the presence of a prolonged HV interval decreased the incidence of sudden death. Therefore, the evaluation of the risk of sudden death should be re-checked by ECG every year. Ventricular arrhythmias are the second mechanism evoked to explain sudden death but the method of identifying MD patients at risk is unknown. Ventricular arrhythmias induced during electrophysiological study do not predict spontaneous ventricular arrhythmias.16
We can only suggest discussing the implantation of an implantable cardioverter defibrillator instead of a pacemaker in MD patients with prolonged HV interval and depressed left ventricular ejection fraction below 30%.26
Breton and Mathieu11
proposed integrating the analysis of QT interval on resting ECG to identify MD patients at risk of sudden death or pacemaker implantation. In presence of a QT interval longer than 450 ms the age-adjusted RR was 3. However, rigorous analysis of the QT interval remains a major problem.27
An automatic analysis and a dynamic analysis on 24 h ECG with the help of new software could be interesting to limit the variability of the QT interval measurement.
SA-ECG is a useful tool in evaluating the infrahissian conduction characteristics of MD patients.15
Babuty et al15
demonstrated that an association of QRSD of 100 ms or greater and LAS of 36 ms or greater selects patients with a prolonged HV interval of 70 ms or greater with high sensitivity (80%) and specificity (83.3%). In the present study significant changes in the SA-ECG correlate with prolonged HV interval in three of six patients. The combination of resting ECG and SA-ECG appears to be the best method of identifying patients showing an alteration over time of the infrahissian conduction time, with excellent sensitivity (100%) and acceptable specificity (75%). However, the usefulness of SA-ECG to identify MD patients with prolonged infrahisian conduction has not been validated by an another group.
Limitations of the study
The fact that not all the patients without a pacemaker were systematically re-investigated could introduce a bias in this study. However, we have verified that the clinical characteristics of the 25 patients included in the study did not differ statistically from the 45 patients not re-investigated for different reasons ( and ).
Some patients could have a normal ECG and prolonged HV interval due to a short AH interval.12
These patients, however, can be identified by the SA-ECG, which, as previously mentioned in the discussion, accurately reveals infrahissian conduction abnormalities.
For the moment there is no randomised, controlled study in the literature clearly indicating that preventive pacemaker implantation in patients with a HV interval greater than 70 ms decreases mortality and morbidity in MD. Only observational and non-controlled studies suggest a real benefit from the prophylactic implantation of a pacemaker in the presence of a prolonged HV interval of 70 ms or greater.12 13