Relationship Between Obstructive Sleep Apnea and Late Gadolinium Enhancement and Their Effect on Cardiac Arrhythmias in Patients with Hypertrophic Obstructive Cardiomyopathy

Figures & data

Table 1 Baseline Characteristics of the Study Population

Variable	None OSA (n=67)	Mild OSA (n=45)	Moderate OSA (n=24)	Severe OSA (n=15)	p
Age, years	43.7±14.4	54.44±11.2	55.6±11.6	49.3±11.1	<0.001
Male	41 (61.2%)	26 (57.8%)	15 (62.5%)	11 (73.3%)	0.650
Body mass index, kg/m^2	24.2±2.7	25.0±3.1	24.7±2.7	26.1±2.6	0.099
Family history of HCM or SCD	18 (26.9%)	5 (11.1%)	3 (12.5%)	1 (6.7%)	0.023
NYHA class	2.8±0.5	2.7±0.4	2.8±0.4	2.7±0.6	0.681
Fasting blood glucose, mmol/L	4.4±0.7	4.8±0.8	5.0±1.2	5.6±2.3	<0.001
BNP, pg/mL	1400 (581.9–2116)	1189 (521.8–2707)	1181 (481.7–1755)	1444 (652.2–2116)	0.895
Norepinephrine, ng/mL	0.28±0.05	0.31±0.08	0.34±0.12	0.38±0.09	<0.001
Clinical presentation
Chest pain	17 (25.4%)	8 (17.8%)	9 (37.5%)	6 (40.0%)	0.195
Amaurosis	10 (15.2%)	7 (15.6%)	3 (15.2%)	2 (13.3%)	0.985
History of syncope	8 (11.9%)	7 (15.6%)	6 (25.0%)	7 (46.7%)	0.013
Medical therapy
Beta-blockers	44 (65.7%)	34 (75.6%)	15 (62.5%)	11 (73.3%)	0.604
Calcium-channel blockers	10 (14.9%)	8 (17.8%)	1 (4.2%)	3 (20.0%)	0.175
Concomitant disease
Diabetes mellitus	3 (4.5%)	3 (6.7%)	1 (4.2%)	2 (13.3%)	0.594
Hypertension	7 (10.4%)	11 (24.4%)	5 (20.8%)	3 (20.0%)	0.250
Apnea hypopnea index, 1/h	1.5±1.3	8.3±2.7	20.7±4.2	43.7±14.6	<0.001
Oxygen desaturation index, 1/h	2.6 (1.0–6.3)	8.6 (6.5–11.1)	17.7 (12.6–23.8)	36.7 (27.3–50.6)	<0.001
Lowest SpO2, %	83.5±8.4	81.4±9.4	77.7±8.0	71.5±8.4	<0.001
Time ratio of SpO2 <90%, %	0.7 (0.0–12.9)	1.4 (0.5–7.4)	10.3 (2.5–15.3)	27.1 (13.5–52.3)	0.001
Total sleep time, min	529.7±99.1	527.4±108.6	504.6±78.1	520.6±86.7	0.743

Abbreviations: OSA, obstructive sleep apnea; HCM, hypertrophic cardiomyopathy; SCD, sudden cardiac death; NYHA, New York Heart Association; BNP, brain natriuretic peptide; LVEDD, left ventricular end-diastolic diameter; IVST, interventricular septal thickness; LVOT, left ventricular outflow tract; LVEF, left ventricular ejection fraction; SpO2, oxygen saturation.

Table 2 Imaging Parameters of the Study Population

Variable	None OSA (n=67)	Mild OSA (n=45)	Moderate OSA (n=24)	Severe OSA (n=15)	p
Echocardiographic indices
LVEF, %	67.9±6.0	67.8±5.7	68.5±6.2	67.3±6.8	0.940
Left atrial diameter, mm	42.9±6.7	44.9±5.9	44.8±7.6	47.9±7.7	0.063
LVEDD, mm	40.5±3.9	42.6±4.6	44.3±4.1	45.7±4.9	<0.001
IVST, mm	21.6±5.6	20.8±4.1	19.8±3.4	21.4±3.8	0.453
LVOT gradient, mmHg	69.7±24.4	72.5±21.3	75.7±27.3	74.5±23.4	0.711
LVOT obstruction at rest	49 (73.1%)	35 (77.8%)	21 (87.5%)	14 (93.3%)	0.041
Pulmonary hypertension	6 (9.0%)	7 (15.6%)	2 (8.3%)	2 (13.3%)	0.692
Cardiac magnetic resonance
Indexed LV mass, g/m^2	93.9±27.1	90.5±23.9	95.0±29.2	126.3±56.0	0.001
Indexed LV volume, mL/m^2	88.6±28.9	86.5±23.0	93.5±31.3	115.4±52.6	0.014
Indexed LGE mass, g/m^2	5.9 (3.5–10.4)	5.6 (3.1–8.3)	9.3 (5.2–13.5)	14.0 (10.7–23.3)	0.038
Indexed LGE volume, mL/m^2	5.6 (3.3–9.9)	5.4 (2.9–7.9)	8.8 (5.0–12.8)	13.4 (10.2–22.2)	0.032
LGE, % of LV mass	6.1 (3.4–10.0)	6.8 (3.6–12.9)	9.6 (5.5–14.5)	15.5 (9.3–20.0)	0.003

Abbreviations: OSA, obstructive sleep apnea; VEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; IVST, interventricular septal thickness; LVOT, left ventricular outflow tract; LGE, late gadolinium enhancement.

Table 3 Clinical Variables Associated with LGE% from Univariate and Multivariate Analysis

Variable	Univariate		Multivariate Adjusted R^2=0.264
	r	p	β	p
Age	−0.025	0.751
Sex	−0.177	0.021
History of syncope	0.159	0.040
NYHA class	0.211	0.006	0.174	0.018
Left atrial diameter	0.142	0.066
IVST	0.161	0.037	0.163	0.026
Apnea hypopnea index, 1/h	0.278	<0.001	0.286	<0.001
Oxygen desaturation index, 1/h	0.247	0.001
Time ratio of SpO2 <90%, %	0.163	0.034

Abbreviations: LGE, late gadolinium enhancement; NYHA, New York Heart Association; IVST, interventricular septal thickness.

Figure 1 Representative LGE and non-sustained ventricular tachycardia image from patients. (A, B) The 4-chamber long-axis and left ventricular short-axis image from a patient who have severe OSA with a value of 13.99%LGE (arrow); (C) the representative non-sustained ventricular tachycardia image from the same patient; (D–E) the 4-chamber long-axis and left ventricular short-axis image from a patient who have severe OSA with a value of 21.88%LGE (arrow).

Table 4 Relationship Between Arrhythmias and OSA

Variable	None OSA (n=67)	Mild OSA (n=45)	Moderate OSA (n=24)	Severe OSA (n=15)	p
Isolated PVC	4 (6.0%)	11 (24.4%)	6 (25.0%)	7 (46.7%)	0.028
Paired PVC	13 (19.4%)	13 (28.9%)	11 (45.8%)	7 (46.7%)	0.036
Ventricular bigeminy	6 (9.0%)	11 (24.4%)	5 (20.8%)	7 (46.7%)	0.005
Ventricular trigeminy	3 (4.5%)	6 (13.3%)	6 (25.0%)	7 (46.7%)	<0.001
NSVT	8 (11.9%)	7 (15.6%)	8 (33.3%)	8 (53.3%)	0.001
Isolated PAC	9 (13.4%)	7 (15.6%)	8 (33.3%)	6 (40.0%)	0.032
Paired PAC	20 (29.9%)	21 (46.7%)	7 (29.2%)	7 (46.7%)	0.211
Atrial bigeminy	8 (11.9%)	9 (20.0%)	3 (12.5%)	6 (40.0%)	0.060
Atrial trigeminy	6 (9.0%)	4 (8.9%)	1 (4.2%)	2 (13.3%)	0.791
SVT	14 (20.9%)	18 (40.0%)	10 (41.7%)	8 (53.3%)	0.029
Atrial fibrillation	6 (9.0%)	9 (20.0%)	7 (29.2%)	3 (20.0%)	0.045
Sinus arrest	5 (7.5%)	5 (11.1%)	3 (12.5%)	1 (6.7%)	0.835
Ectopic beat	0 (0.0%)	1 (2.2%)	1 (4.2%)	0 (0.0%)	0.413

Abbreviations: OSA, obstructive sleep apnea; PVC, premature ventricular contraction; NSVT, non-sustained ventricular tachycardia; PAC, premature atrial contraction; SVT, supraventricular tachycardia.

Figure 2 The value of late gadolinium enhancement according to the presence of various arrhythmias between patients with and without arrhythmias. (A) Premature ventricular contractions; (B) paired premature ventricular contractions; (C) ventricular bigeminy; (D) ventricular trigeminy; (E) premature atrial contractions; (F) atrial bigeminy; (G) non-sustained ventricular tachycardia; (H) supraventricular tachycardia.

Table 5 Adjusted Logistic Regression Among Arrhythmias and Significant Variables from Univariate Analysis

Variable	Univariate		Multivariate
	OR (95% CI)	p	OR (95% CI)	p
Isolated PVC
Apnea hypopnea index, 1/h	1.05 (1.02–1.08)	0.001	1.04 (1.008–1.08)	0.001
LGE, % of LV mass	1.06 (1.004–1.12)	0.037	1.07 (1.004–1.15)	0.039
Paired PVC
LGE, % of LV mass	1.06 (1.01–1.12)	0.0.16	1.06 (1.004–1.11)	0.034
Glucose	1.68 (1.12–2.50)	0.012	1.67 (1.11–2.49)	0.014
Ventricular bigeminy
Apnea hypopnea index	1.04 (1.01–1.07)	0.003	1.26 (1.11–1.62)	0.002
LGE % of LV mass	1.05 (1.02–1.10)	0.050	1.04 (1.01–1.07)	0.003
Ventricular Trigeminy
Male	0.29 (0.12–0.71)	0.007	0.29 (0.11–0.84)	0.022
Apnea hypopnea index	1.06 (1.03–1.09)	<0.001	1.06 (1.02–1.09)	0.001
LVOT gradient	0.98 (0.95–0.99)	0.036	0.97 (0.93–0.99)	0.035
LGE % of LV mass	1.11 (1.05–1.18)	0.001	1.07 (1.003–1.15)	0.040
Isolated PAC
Male	2.29 (1.09–4.83)	0.030	3.04 (1.28–7.20)	0.012
Left atrium diameter	1.07 (1.008–1.14)	0.026	1.10 (1.03–1.18)	0.006
Apnea hypopnea index	1.03 (1.006–1.06)	0.017	1.04 (1.006–1.07)	0.017
NSVT
Apnea hypopnea index	1.08 (1.04–1.12)	<0.001	1.08 (1.04–1.13)	<0.001
Family history of HCM or SCD	2.89 (1.16–7.18)	0.023	7.02 (1.92–25.69)	0.003
LGE % of LV mass	1.19 (1.11–1.28)	<0.001	1.17 (1.09–1.26)	<0.001
SVT
Age	1.04 (1.01–1.08)	0.005	1.12 (1.06–1.19)	<0.001
Left atrium diameter	1.12 (1.06–1.19)	<0.001	1.05 (1.01–1.08)	0.006
Atrial fibrillation
Apnea hypopnea index	1.03 (1.000–1.05)	0.05	1.04 (1.005–1.07)	0.006
Left atrium diameter	1.09 (1.02–1.17)	0.009	4.14 (1.33–12.93)	0.01

Notes: Adjusted for age, sex, body mass index, and other relevant covariates (variables with p<0.10 on univariate analysis).

Abbreviations: PVC, premature ventricular contraction; LGE, late gadolinium enhancement; NSVT, non-sustained ventricular tachycardia; PAC, premature atrial contraction.