Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 14, Number 6, December 2023, pages 446-452

The Heart of Rett Syndrome: A Quantitative Analysis of Cardiac Repolarization

Figure 1. Depiction of the electrocardiographic measurements along with T-wave morphology characteristics seen in the study’s RTT patients. (a) Normal T wave. (b) Prolonged QT with prolonged JTp. (c) Asymmetric T wave. (d) Notched T wave. (e) Flat T wave. This ECG had the highest morphology combination score (MCS). ECG: electrocardiogram; RTT: Rett syndrome; JTp: time from the J point to the peak of the T wave.

Figure 2. Distribution of patients with and without repeated prolonged QTc on ECG by RTT genotype. The black bar is the percentage of patients with repeated prolonged QTc on ECG. The gray bar is the percentage of patients without repeated prolonged QTc (i.e., patients with only one prolonged QTc on ECG or patients with no prolonged QTc on ECG). For each column, the percentage of patients with repeated prolonged QTc and the percentage of patients without repeated prolonged QTc add up to 100%. Clinical: clinical RTT as defined in the text; Uncommon: identified mutations besides R106W, R133c, R168X, R255X, R270X, R294x, R306C, R306H, T158M; QTc: corrected QT; ECG: electrocardiogram; RTT: Rett syndrome.

**Table 1.** Baseline and Electrocardiographic Characteristics
	Control (n = 124)	All RTT (n = 110)	MECP2 (n = 78)	CDKL5 (n = 8)	FOXG1 (n = 3)	Clinical RTT (n = 21)	P control vs. all RTT
Values are counts (%) or means (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; bpm: beats per minute.
Long QT	6 (4.8)	55 (50)	45 (57.6)	1 (12.5)	0 (0)	9 (42.8)	< 0.001
Mean age, years	9.3 (5.2)	11.7 (8.5)	10.7 (7.6)	5.9 (5.4)	4.1 (2.5)	18 (9.6)	< 0.001
Heart rate, bpm	87.1 (24.1)	95 (21.8)	94 (20.9)	110.6 (14.4)	123 (14.3)	92.6 (24.9)	< 0.001
QTc, ms	422.8 (19.3)	445.6 (31.6)	448 .1 (32.8)	430.2 (17.6)	430.4 (12.8)	440.8 (28.8)	< 0.001

Table 1. Baseline and Electrocardiographic Characteristics

Control (n = 124)

All RTT (n = 110)

MECP2 (n = 78)

CDKL5 (n = 8)

FOXG1 (n = 3)

Clinical RTT (n = 21)

P control vs. all RTT

Values are counts (%) or means (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; bpm: beats per minute.

Long QT

6 (4.8)

55 (50)

45 (57.6)

1 (12.5)

0 (0)

9 (42.8)

< 0.001

Mean age, years

9.3 (5.2)

11.7 (8.5)

10.7 (7.6)

5.9 (5.4)

4.1 (2.5)

18 (9.6)

< 0.001

Heart rate, bpm

87.1 (24.1)

95 (21.8)

94 (20.9)

110.6 (14.4)

123 (14.3)

92.6 (24.9)

< 0.001

QTc, ms

422.8 (19.3)

445.6 (31.6)

448 .1 (32.8)

430.2 (17.6)

430.4 (12.8)

440.8 (28.8)

< 0.001

**Table 2.** Comparison of T wave Analysis Characteristics
	Control (n = 124)	All RTT (n = 110)	MECP2 (n = 78)	CDKL5 (n = 8)	FOXG1 (n = 3)	Clinical RTT (n = 21)	P control vs. all RTT
Values are mean (SD). SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.
Corrected JTp, ms	189.6 (30.6)	193.3 (37.6)	196.3 (36.7)	156.7 (18.9)	144.5 (13.4)	195.1. (38.8)	0.169
TpTe, ms	91.3 (10.4)	96.4 (19.9)	96.6 (20.9)	89.9 (12)	94.8 (11.5)	93.3 (17.5)	0.343
MCS	60.7 (24.6)	97.8 (59)	106.4 (61.8)	55.1 (18.8)	50.3 (30.7)	78.1 (42)	< 0.001
Flatness score	27.3 (11.8)	35.6 (13.4)	37.3 (13.3)	23.4 (6.7)	19.9 (6.5)	33.1 (13.1)	0.005
Asymmetry score	15.6. (10.8)	25.9 (22.6)	28.3 (22.9)	16.9 (12.8)	11.3(10.4)	19.6 (22.2)	< 0 .001
Notch score	0 (0.4)	2 (8.1)	2.5 (9.3)	0 (0)	0.38 (1.1)	0.2 (1)	0.002
PCA-2, %	19.2 (9.1)	25.5 (13.2)	25.2 (13)	25.6 (10.3)	31.2 (7.3)	26.1 (15.2)	< 0.001

Table 2. Comparison of T wave Analysis Characteristics

Control (n = 124)

All RTT (n = 110)

MECP2 (n = 78)

CDKL5 (n = 8)

FOXG1 (n = 3)

Clinical RTT (n = 21)

P control vs. all RTT

Values are mean (SD). SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.

Corrected JTp, ms

189.6 (30.6)

193.3 (37.6)

196.3 (36.7)

156.7 (18.9)

144.5 (13.4)

195.1. (38.8)

0.169

TpTe, ms

91.3 (10.4)

96.4 (19.9)

96.6 (20.9)

89.9 (12)

94.8 (11.5)

93.3 (17.5)

0.343

MCS

60.7 (24.6)

97.8 (59)

106.4 (61.8)

55.1 (18.8)

50.3 (30.7)

78.1 (42)

< 0.001

Flatness score

27.3 (11.8)

35.6 (13.4)

37.3 (13.3)

23.4 (6.7)

19.9 (6.5)

33.1 (13.1)

0.005

Asymmetry score

15.6. (10.8)

25.9 (22.6)

28.3 (22.9)

16.9 (12.8)

11.3(10.4)

19.6 (22.2)

< 0 .001

Notch score

0 (0.4)

2 (8.1)

2.5 (9.3)

0 (0)

0.38 (1.1)

0.2 (1)

0.002

PCA-2, %

19.2 (9.1)

25.5 (13.2)

25.2 (13)

25.6 (10.3)

31.2 (7.3)

26.1 (15.2)

< 0.001

**Table 3.** QTc and T-wave Parameters by RTT Mortality
	RTT living (n = 105)	RTT deceased (n = 5)	P
Values are mean (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.
QTc, ms	446.8. (29.9)	432.9 (43.1)	0.903
Corrected JTp, ms	192 (36.7)	206.3 (44)	0.029
TpTe, ms	96.7 (18.6)	93.6 (29.4)	0.391
MCS	94.8 (56.2)	127.3 (75.7)	0.001
Flatness score	35.2 (12.9)	39.4 (17.3)	0.038
Asymmetry score	24.9 (21.3)	35.6 (31.2)	< 0.001
Notch score	1.8 (8.11)	3.3 (8.3)	0.028
PCA-2, %	25.3 (12.6)	27 (18.3)	0.043

Table 3. QTc and T-wave Parameters by RTT Mortality

RTT living (n = 105)

RTT deceased (n = 5)

Values are mean (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.

QTc, ms

446.8. (29.9)

432.9 (43.1)

0.903

Corrected JTp, ms

192 (36.7)

206.3 (44)

0.029

TpTe, ms

96.7 (18.6)

93.6 (29.4)

0.391

MCS

94.8 (56.2)

127.3 (75.7)

0.001

Flatness score

35.2 (12.9)

39.4 (17.3)

0.038

Asymmetry score

24.9 (21.3)

35.6 (31.2)

< 0.001

Notch score

1.8 (8.11)

3.3 (8.3)

0.028

PCA-2, %

25.3 (12.6)

27 (18.3)

0.043

**Table 4.** QTc and T-Wave Parameters Between Control With QTc < 460 ms and RTT With QTc < 460 ms
	Control (n = 118)	RTT (n = 55)	P
Values are means (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.
QTc, ms	420.55 (16.82)	431.31 (19.82)	< 0.001
Corrected JTp, ms	189.14 (30.39)	188.12 (36.43)	0.117
TpTe, ms	90.91 (10.31)	95.37 (18.91)	0.186
MCS	59.86 (24.34)	89.61 (54.29)	< 0.001
Flatness score	27.03 (11.80)	33.71 (13.39)	0.007
Asymmetry score	15.11 (10.57)	23.72 (21.95)	< 0.001
Notch score	0.04 (0.42)	1.32 (6.23)	0.004
PCA-2, %	18.65 (8.36)	25.37 (13.35)	< 0.001

Table 4. QTc and T-Wave Parameters Between Control With QTc < 460 ms and RTT With QTc < 460 ms

Control (n = 118)

RTT (n = 55)

Values are means (SD). QTc: corrected QT; SD: standard deviation; RTT: Rett syndrome; MCS: morphology combination score; PCA-2: principal component analysis ratio; JTp: time from the J point to the peak of the T wave; TpTe: time from the peak of the T wave to the end of the T wave.

QTc, ms

420.55 (16.82)

431.31 (19.82)

< 0.001

Corrected JTp, ms

189.14 (30.39)

188.12 (36.43)

0.117

TpTe, ms

90.91 (10.31)

95.37 (18.91)

0.186

MCS

59.86 (24.34)

89.61 (54.29)

< 0.001

Flatness score

27.03 (11.80)

33.71 (13.39)

0.007

Asymmetry score

15.11 (10.57)

23.72 (21.95)

< 0.001

Notch score

0.04 (0.42)

1.32 (6.23)

0.004

PCA-2, %

18.65 (8.36)

25.37 (13.35)

< 0.001