2.1 Basic data of patients
From January 1, 2023 to April 30, 2023, there were total of 1456 patients who underwent 24 h Holter ECG examination after COVID-19, further continuous selection of 998 outpatients to the next step of filtering. Among them, 168 patients who had undergone at least once 24 h Holter ECG examination between January 1, 2018 and December 20, 2022 were selected. There are 24 patients excluded the study according to exclusion criteria, a total of 144 patients were included(Figure.1). Among them 67 were males, with an average age of 56 ± 14.3 years. There were 12 underwent 24 h Holter ECG examination within 2 weeks of infection, 20 within 2-4 weeks, and 112 within 1-5month. The baseline of patients was show in Table 1. Hypertension and coronary heart disease were the most common diseases, accounting for 44% and 21% respectively in our study. Most patients experienced palpitations and chest tightness in clinical symptoms.
Table 1 Overall characteristics of the included population
Sex,n(%)
|
N=144
|
Male
|
67
|
Female
|
77
|
Basic diseases
|
N=236
|
Hypertension
|
104(44%)
|
Diabetes mellitus
|
33(14%)
|
Coronary heart disease
|
49(21%)
|
Valvular heart disease
|
8(3%)
|
Hyperthyroidism
|
10(24%)
|
Congenital heart disease
|
2(1%)
|
Others
|
30(13%)
|
Symptoms
|
N=353
|
Palpitate
|
95(27%)
|
Insomnia
|
28(8%)
|
Chest tightness
|
78(22%)
|
Dizziness
|
23(6%)
|
Chest pain
|
15(4%)
|
Feeble
|
31(9%)
|
Headache
|
27(8%)
|
Others
|
56(16%)
|
Table 1 Abbreviation: Other basic diseases include chronic obstructive pulmonary disease and arrhythmia. Some young patients with only symptoms but no Basic diseases are also classified in this category. The diagnosis of basic diseases in all patients was before two 24 h Holter ECG examinations. Other symptoms include chest tightness, cough, asthma after activities, decreased activity tolerance or asymptomatic patients who underwent 24 h Holter ECG examinations only because they fear that COVID-19 will damage the cardiovascular system.Due to some patients having more than one basic diseases or clinical symptoms, the total number of basic diseases or symptoms exceeded the included population.
2.2 Changes in 24 h Holter ECG before and After COVID-19
The average heart rate difference before and after COVID-19 was 2.23 ± 7.87 beats per minute, with a 95% CI of -3.526 to -0.932. The average heart rate was higher after COVID-19 infection (72.10 ± 8.48 vs. 69.88 ± 8.10 bpm; p = 0.001). The difference in the minimal heart rate between before and after COVID-19 was 2.44 ± 7.18 beats per minute, with a 95% CI of -3.620 to -1.255. The minimal heart rate after COVID-19 was higher than before-infection (51.94 ± 8.43 vs. 49.51 ± 6.89 bpm; p <0.001) . There was no statistically significant difference in the maximal heart rate between before and after COVID-19. The median number of premature beat in before-COVID-19 was 14.00 (IQR 3.00-83.00), and 19.50 (IQR 4.00-98.50) in after-COVID-19. The median number of atrial tachycardia in before-COVID-19 was 0.00 (IQR 0.00-1.00), and 0.00 (IQR 0.00-1.75) after-COVID-19. The median number of Ventricular premature contractions bigeminy in before-COVID-19 was 0.00 (IQR 0.00-0.00), and 0.00 (IQR 0.00-1.00) after-COVID-19.The above arrhythmias increased between before and after COVID-19, and the difference was statistically significant (P<0.05). There was no statistically significant difference (P>0.05) in Paired atrial premature contractions, atrial premature contractions bigeminy, atrial premature contractions trigeminy, total number of ventricular premature contractions, paired premature ventricular, ventricular premature contractions trigeminy, and ventricular tachycardia between before and after COVID-19. There were 54 cases had T wave changes before COVID-19, and 71 cases after COVID-19, the difference was statistically significant increased (49.31% vs. 37.50% p <0.05). The incidence of ST segment changes, bundle branch block, and atrioventricular block did not show significant differences between before and after COVID-19 infection (P>0.05) (Table 2).
Table 2 Changes in heart rate,premature beat and others between pre and after COVID-19 infection
|
N=144
|
|
Before-COVID
|
After-COVID
|
P value
|
Heart rate(Times/minute),mean±SD
|
|
|
|
Average heart rate
|
69.88±8.10
|
72.10±8.48
|
0.001
|
Minimal heart rate
|
49.51±6.89
|
51.94±8.43
|
<0.001
|
Maximal heart rate
|
115.44±17.35
|
117.22±15.89
|
0.173
|
Premature beat(Pieces/burst) M P25-P75
|
|
|
|
Total number of atrial premature beats
|
14.00(3.00-83.00)
|
19.50(4.00-98.50)
|
0.021
|
Paired atrial premature beats
|
0(0.00-2.00)
|
0(0.00-2.00)
|
0.400
|
Atrial premature bigeminy
|
0(0.00-0.00)
|
0(0.00-0.00)
|
0.465
|
Atrial premature trigeminy
|
0(0.00-0.00)
|
0(0.00-0.00)
|
0.280
|
Atrial tachycardia
|
0(0.00-1.00)
|
0(0.00-1.75)
|
0.031
|
Total number of ventricular premature beats
|
12.00(0.00-1017.00)
|
36.50(1.00-2963.50)
|
0.158
|
Paired ventricular premature beats
|
0(0.00-0.00)
|
0(0.00-0.00)
|
0.195
|
Ventricular premature bigeminy
|
0(0.00-0.00)
|
0(0.00-1.00)
|
0.001
|
Ventricular premature trigeminy
|
0(0.00-0.00)
|
0(0.00-8.00)
|
0.291
|
Ventricular tachycardia
|
0(0.00-0.00)
|
0(0.00-0.00)
|
0.532
|
Others,n(%)
|
|
|
|
ST segment depression
|
58(40.28)
|
69(47.92)
|
0.100
|
T-wave changes
|
54(37.50)
|
71(49.31)
|
0.004
|
Bundle branch block
|
9(6.30)
|
11(7.64)
|
0.617
|
Atrioventricular block
|
8(5.56)
|
6(4.17)
|
0.683
|
2.3 Changes in HRV before and after COVID-19
Regarding HRV indicators between before and after COVID-19, the median SDNN was 134.50 (IQR 111.00-161.75) ms before COVID-19, while decreased after COVID-19, with a median of 126.50 (IQR 104.25-157.00) ms. The median SDNN index was 51.00 (IQR 42.00-69.75) ms before COVID-19, while decreased with a median of 48.00 (IQR 39.00-67.00) ms after COVID-19.The median PNN50 was 7.00 (IQR 3.00-14.00)% beforeCOVID-19, while decreased with a median of 6.60 (IQR 2.00-13.00)% after COVID-19.The median HF was 156.00 (IQR 93.50-342.15) beforeCOVID-19, while decreased with a median of 139.00 (IQR 58.50-282.95) after COVID-19.The median LF was 362.00 (IQR 204.25-649.45) beforeCOVID-19, while decreased with a median of 318.00 (IQR 124.30-575.00) after COVID-19.The differences were statistically significant (P<0.05). There was no statistically significant difference in RMSSD, TID, and VLF (P>0.05)(Table 3).
Table 3 Changes in heart rate variability between before and after COVID-19 infection
|
N=144
|
|
Before COVID
|
After COVID
|
P value
|
SDNN(ms)
|
134.50(111.00-161.75)
|
126.50(104.25-157.00)
|
0.033
|
SDNN index(ms)
|
51.00(42.00-69.75)
|
48.00(39.00-67.00)
|
0.011
|
RMSSD(ms)
|
31.00(23.25-47.25)
|
30.00(22.00-43.75)
|
0.503
|
PNN50(%)
|
7.00(3.00-14.00)
|
6.60(2.00-13.00)
|
0.030
|
TID
|
23.00(17.00-31.75)
|
21.00(15.00-30.00)
|
0.642
|
HF
|
156.00(93.50-342.15)
|
139.00(58.50-282.95)
|
0.019
|
LF
|
362.00(204.25-649.45)
|
318.00(124.30-575.00)
|
0.001
|
VLF
|
1029.00(747.50-1580.50)
|
1065.00(642.53-1616.75)
|
0.806
|
Abbreviation: SDNN,standard deviation of all normal RR intervals ; SDNN index,mean standard deviation of RR intervals ; rMSSD , root mean square value of the difference between adjacent RR intervals throughout the entire process; PNN50, percentage of adjacent RR intervals with a difference greater than 50 ms to the total number of sinus beats; TID, trigonometric index; HF, high-frequency ; LF, Low frequency ; VLF,Very low frequency .