Sample characteristics, assessment methods and key findings of the eligible studies for systematic review: sudden death
| Study | N | Participant age | Mutation/diagnosis | Assessment methods | Key findings |
|---|---|---|---|---|---|
| Guideri et al.49 (1999) | 54 RTT (F) 28 healthy controls (F) | Mean ± SD: RTT 10 ± 5.5 yr Healthy controls 9.71 ± 4.6 yr | RTT diagnosis confirmed in each patient, alongside clinical stage based on Hagberg and Witt-Engerstrom71 | 12-lead ECG along with spectral component measurements (VLF, LF and HF) and QTc analyses | LF/HF ratio was significantly higher in the RTT group across all 4 stages compared with healthy controls HR variability (R-R interval) was significantly lower in the RTT group compared with healthy controls Decreased HR variability was suggested to be a risk factor for sudden death in RTT |
| Guideri et al.75 (2004) | 32 RTT (F) 30 age-matched healthy controls (F) | RTT 4 ± 4.1 yr Healthy controls 6.8 ± 2.1 yr | Patients recruited from the Department of Child Neurology, University of Siena | Echocardiography to examine structural abnormalities and blood flow of the heart ECG and spectral component measurements (VLF, LF and HF) and QTc | LF/HF was significantly higher in the RTT group compared with healthy controls (3.8 ± 2.9 v. 1 ± 0.5; p < 0.001) QTc interval was significantly longer in the RTT group (0.44 ± 0.02) compared to healthy controls (0.40 ± 0.01; p < 0.001) No difference in echocardiography findings between the RTT group and healthy controls |
| Guideri et al.52 (2005) | 22 RTT (10 active treatment; 12 untreated)* | Mean ± SD: Active treatment 6.3 ± 4.3 yr Untreated 6.3 ± 4.0 yr | RTT diagnosis confirmed by 2 child neuropsychiatrists | Spectral waveform 12-lead ECG, along with spectral components (VLF, LF and HF) and QTc analyses | Examined the premises that reduced HR variability in RTT causes sudden death and that acetyl-L-carnitine might increase HR variability and have a protective affect on the cardiac system In the untreated group, total power and LF decreased significantly from baseline values after 6–18 mo; QTcD was elevated After 6 mo of acetyl-L-carnitine treatment, total power (p = 0.01), VLF (p = 0.01) and LF (p = 0.009) increased significantly compared to basal values No statistically significant difference (p = 0.6) in R-R interval between the active treatment and untreated groups at baseline or at follow-up Acetyl-L-carnitine might have a cardioprotective effect on the ANS and might decrease the frequency of sudden cardiac death in patients with RTT |
| Julu et al.76 (1997) | 6 RTT (F) 8 controls (F) | RTT 4–11 yr Controls 4–11 yr | Information not available | NeuroScope alongside measures such as chest plethysmograph and MAP measurements | In the RTT group, mean ± SEM CVT was 3.6 ± 0.7 units v. 10.5 ± 0.9 units in the control group (p < 0.001) MAP was 94.6 ± 6.4 mmHg in controls v. 78 ± 4.33 mmHg in patients with RTT Vagal tone was disrupted during hyperventilation Immaturity of medullary cardiorespiratory neurons contribute to autonomic disturbances that could result in sudden death in people with RTT |
| Sekul et al.77 (1994) | 34 RTT† 41 controls | RTT 2–22 yr Controls 2–18 yr | RTT diagnosis confirmed in each patient, alongside clinical stage based on Hagberg and Witt-Engerstrom71 by 1 or more of the investigators | ECG parameters | Patients with RTT had longer QTc intervals (p < 0.001) and T-wave abnormalities (p < 0.001) compared to age-matched controls In patients with RTT with T-wave abnormalities, the frequency tended to increase from Stage II (36%) to Stage III (69%) and Stage IV (70%) Changes in T-waves and QTc were highlighted as risk factors that might contribute to sudden death patients with RTT |
ANS = autonomic nervous system; CVT = cardiac vagal tone; ECG = electrocardiogram; HF = high frequency; HR = heart rate; LF = low frequency; MAP = mean arterial pressure; QT = Q and T waves on electrocardiogram; QTc = corrected QT; QTcD = QTc dispersion; R-R = inter-beat interval; RTT = Rett syndrome; SD = standard deviation; SEM = standard error of the mean; VLF = very low frequency.
↵* Ten girls with RTT were randomized to receive active treatment and 12 girls with RTT were age-matched untreated controls.
↵† Data from 61 ECGs (12-lead) were obtained from 34 patients with RTT.