Evaluation of heart rate variability in pediatric patients with beta thalassemia major: Cross-sectional study

Table 1 Comparison between the two studied groups regarding demographic, clinical, and laboratory data, mean ± SD/median (25^th-75^th percentiles)

Parameter	β-thalassemia (n = 40)	Controls (n = 40)	P value
Age (years)	9.24 ± 4.01	7.88 ± 3.82	0.124
Sex (male/female)	22/18	18/22	0.371
Weight (kg)	26.15 ± 9.94	34.40 ± 14.41	0.020
Height (m)	1.20 ± 0.20	1.32 ± 0.25	0.022
BMI (kg/m2)	17.57 ± 2.46	18.72 ± 2.60	0.045
Serum ferritin (ng/mL)	970 (690-1712.5)	79 (59-99)	< 0.001
Hb (g/dL)	8.34 ± 0.96	11.08 ± 0.50	< 0.001
PLT (× 103/μL)	364.1 ± 18.20	358.4 ± 12.68	0.104
WBCs (× 103/μL)	10.85 ± 9.68	9.05 ± 1.16	0.376
MCV (fL)	67.8 ± 6.0	80.8 ± 5.2	0.001
MCH (pg)	25.5 ± 2.1	28.7 ± 1.9	0.014
RDW (%)	14.1 ± 1.2	13.8 ± 1.1	0.917
Reticulocytes (%)	6.12 ± 1.5	0.84 ± 0.22	0.001

BMI: Body mass index; Hb: Hemoglobin; PLT: Platelets; WBCs: White blood cells; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; RDW: Red cell distribution width.

Table 2 Comparison between the two studied groups regarding heart rate and heart rate variability parameters, mean ± SD/median (25^th-75^th percentiles)

Parameter	β-thalassemia (n = 40)	Controls (n = 40)	P value
Minimum HR (bpm)	63.35 ± 13.06	58.50 ± 4.44	0.031
Maximum HR (bpm)	161.4 ± 16.98	147.5 ± 5.31	< 0.001
Average HR (bpm)	100.6 ± 13.03	103.3 ± 3.49	0.216
SDNN (ms)	79.18 ± 32.08	137.2 ± 17.53	< 0.001
SDANN5 (ms)	74.43 ± 23.75	122.5 ± 19.89	< 0.001
SDNN index (ms)	41.70 ± 14.85	101.0 ± 20.14	< 0.001
RMSSD (ms)	28.43 ± 13.81	54.13 ± 14.80	< 0.001
pNN50 (%)	8.93 ± 8.12	32.65 ± 11.48	< 0.001
HF power (ms2)	323.4 (239.9-404.1)	537.0 (269.3-872.3)	0.002
LF power (ms2)	670.8 (537.3-814.2)	614.0 (335.0-733.1)	0.125
VLF power (ms2)	1283.3 (1005.2-1441.2)	1240.0 (864.4-2050.5)	1.000
LF/HF ratio	2.11 (1.64-2.68)	1.16 (0.89-1.50)	< 0.001

No significant sex-based or age-dependent differences were observed in heart rate variability parameters among the patient group, suggesting that autonomic dysfunction in β-thalassemia may not be influenced by these demographic factors. HR: Heart rate; SDNN: Standard deviation of all normal-to-normal intervals; SDANN: Standard deviation of the 5-minute average normal-to-normal intervals; RMSSD: Root mean square of successive differences; pNN50: Percentage of successive normal-to-normal intervals differing by > 50 ms; LF: Low frequency; HF: High frequency; VLF: Very low frequency.

Table 3 Presence and type of arrhythmia in patients with β-thalassemia major

Parameter	n (%)
Patients with arrhythmia (group IA)	19 (47.5)
Patients without arrhythmia (group IB)	21 (52.5)
Types of arrhythmia
Infrequent supraventricular ectopic beats	11 (27.5)
Infrequent ventricular ectopic beats	5 (12.5)
Frequent supraventricular ectopic beats	2 (5.0)
Frequent ventricular ectopic beats and non-sustained ventricular tachycardia	1 (2.5)
Benign arrhythmias (e.g., wandering atrial pacemaker)	4 (10.0)

Some patients exhibited more than one arrhythmia type during Holter monitoring.

Table 4 Comparison of heart rate variability parameters between patients with and without arrhythmia, mean ± SD/median (25^th-75^th percentiles)

Parameter	With arrhythmia (n = 19)	Without arrhythmia (n = 21)	P value
Minimum HR (bpm)	63.76 ± 13.16	62.89 ± 13.30	0.837
Maximum HR (bpm)	161.4 ± 19.43	161.4 ± 14.34	0.999
Average HR (bpm)	101.2 ± 11.50	99.89 ± 14.83	0.749
SDNN (ms)	78.24 ± 28.67	80.21 ± 36.26	0.649
SDANN5 (ms)	72.43 ± 23.28	76.63 ± 24.69	0.503
SDNN index (ms)	38.71 ± 11.83	45.00 ± 17.34	0.236
RMSSD (ms)	25.76 ± 13.17	31.37 ± 14.24	0.204
pNN50 (%)	7.48 ± 7.87	10.53 ± 8.30	0.169
HF power (ms2)	326.6 (254.7-349.7)	320.2 (234.4-492.1)	0.776
LF power (ms2)	667.3 (595.7-759.3)	674.2 (447.9-899.9)	0.745
VLF power (ms2)	1289.5 (1234.1-1400.5)	1234.8 (890.8-1436.5)	0.626
LF/HF ratio	1.99 (1.78-2.45)	2.29 (1.57-2.71)	0.818

HR: Heart rate; SDNN: Standard deviation of all normal-to-normal intervals; SDANN: Standard deviation of 5-minute average normal-to-normal intervals; RMSSD: Root mean square of successive differences; pNN50: Percentage of normal-to-normal intervals differing by > 50 ms; LF: Low frequency; HF: High frequency; VLF: Very low frequency.

Table 5 Comparison between the two studied groups regarding different waves and intervals, median (25^th-75^th percentiles)/n (%)

		Patient group (n = 40)	Control group (n = 40)	P value
P wave	Amplitude (mm)	3 (2-3)	2 (2–3)	0.385
	Duration (second)	0.08 (0.08-0.08)	0.08 (0.08-0.09)	0.597
	Dispersion (second)	0.04 (0.04-0.04)	0.035 (0.02-0.04)	< 0.001
QRS complex	R wave amplitude in channel 1 (mm)	25 (23-26)	24 (23-24)	0.004
	R wave amplitude in in channel 2 (mm)	12 (8-15)	7 (4-10)	< 0.001
	S wave amplitude in in channel 1 (mm)	4 (2-7)	5 (3-7)	0.438
	S wave amplitude in channel 2 (mm)	7 (6-9)	7 (5-8)	0.081
	Duration (second)	0.12 (0.11-0.12)	0.08 (0.08-0.08)	< 0.001
PR interval	Constant	40 (100.0)	40 (100.0)
	1:1 AV conduction	40 (100.0)	40 (100.0)
	Duration (second)	0.16 (0.12-0.16)	0.12 (0.12-0.12)	< 0.001
ST segment	Normal	36 (90.0)	40 (100.0)	0.116
	Elevation	0 (0.0)	0 (0.0)
	Depression	4(10)	0 (0.0)	0.116
T wave abnormalities	Normal	39 (97.5)	40 (100.0)	1.000
	Inversion	1 (2.5)	0 (0.0)	1.000
QT corrected (msec)		464.5 (443-481)	405 (380-430)	< 0.001

AV: Atrioventricular.

Table 6 Correlation between serum ferritin, hemoglobin level, and heart rate variability parameters in β-thalassemia patients

Variable	HRV parameter	Spearman’s ρ	P value
Hemoglobin	LF power	0.230	0.154
	HF power	-0.188	0.244
	SDANN	-0.162	0.317
	RMSSD	-0.070	0.666
Serum ferritin	LF power	-0.096	0.557
	HF power	-0.012	0.943
	SDANN	0.194	0.230
	RMSSD	-0.130	0.425

Correlation between heart rate variability indices and laboratory parameters assessed using Spearman’s test. None of the correlations were statistically significant (P > 0.05). LF: Low frequency; HF: High frequency; SDANN: Standard deviation of the 5-minute mean normal-to-normal intervals; RMSSD: Root mean square of successive differences; HRV: Heart rate variability.