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Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy
HLC 3001 1–9
Heart, Lung and Circulation (2019) xx, 1–9 1443-9506/04/$36.00 https://doi.org/10.1016/j.hlc.2019.05.190
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ORIGINAL ARTICLE
Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy [TD$FIRSNAME]Shengwei[TD$FIRSNAME.] [TD$SURNAME]Wang[,TD$SURNAME.] MD a*, [TD$FIRSNAME]Hao[TD$FIRSNAME.] [TD$SURNAME]Cui[TD$SURNAME.], MD b, [TD$FIRSNAME]Liukun[TD$FIRSNAME.] [TD$SURNAME]Meng[TD$SURNAME.], MD a, [TD$FIRSNAME]Rong[TD$FIRSNAME.] [TD$SURNAME]Wu[TD$SURNAME.], MD a, [TD$FIRSNAME]Bing[TD$FIRSNAME.] [TD$SURNAME]Tang[TD$SURNAME.], MD a, [TD$FIRSNAME]Changsheng[TD$FIRSNAME.] [TD$SURNAME]Zhu[TD$SURNAME.], MD a, [TD$FIRSNAME]Qinjun[TD$FIRSNAME.] [TD$SURNAME]Yu[TD$SURNAME.], MD a, [TD$FIRSNAME]Xiaohong[TD$FIRSNAME.] [TD$SURNAME]Huang[TD$SURNAME.], MD c, [TD$FIRSNAME]Shuiyun[TD$FIRSNAME.] [TD$SURNAME]Wang[TD$SURNAME.], MD a a
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China b Q11 Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA c Department of Special Medical Treatment Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Received 22 January 2019; accepted 23 May 2019; online published-ahead-of-print xxx
Background
The prevalence of obstructive sleep apnoea (OSA) is high in patients with hypertrophic cardiomyopathy. The effect of septal myectomy on OSA is not clear. This study aimed to examine the association between hypertrophic obstructive cardiomyopathy and OSA before and after septal myectomy.
Method
We included 85 consecutive patents with a confirmed diagnosis of hypertrophic obstructive cardiomyopathy who underwent septal myectomy. Polysomnography was performed in all patients before and 3 months after the surgery.
Results
Of the 85 patients, 49 (58%) were diagnosed with OSA. Patients with OSA were significantly older than those without OSA. The incidence of atrial fibrillation significantly increased during perioperative period in patients with OSA (p = 0.03). The severity of OSA significantly increased 3 months after surgery, as determined by the apnoea–hypopnea index (AHI; p < 0.001), obstructive apnoea index (p = 0.024), and hypopnoea index (p = 0.003), whereas central apnoea index was decreased (p = 0.008). In the multivariate linear regression analysis, mean oxygen desaturation and time% with SpO2 <90% during sleep before surgery were significantly associated with increased AHI, independently of body mass index and sex (p = 0.026 and p = 0.007, respectively; adjusted R2 = 0.365).
Conclusions
The severity of OSA significantly increased 3 months after septal myectomy as determined by AHI, obstructive apnoea index, and hypopnoea index. Mean oxygen saturation and time% with SpO2 <90% during sleep before surgery were independently associated with the increase of AHI. However, the specific mechanism of such deterioration of OSA after septal myectomy needs to be determined in detail.
Keywords
Obstructive sleep apnea Septal myectomy Hypertrophic cardiomyopathy Atrial fibrillation Sleep disorder Polysomnography
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*Corresponding author at: 167 Beilishi Road, Xicheng District, Beijing 100037, China. Tel./ fax: +86-10-88396636/+86-10-68330739., Email: [email protected] © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Introduction
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Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease, with a prevalence of approximately 1:500 in the general population. About two-thirds of patients with HCM have left ventricular outflow tract obstruction (LVOTO). If the symptoms of these patients are refractory to optimal pharmacological therapy, septal myectomy is recommended [1]. Although the surgical treatment of hypertrophic obstructive cardiomyopathy (HOCM) has a good prognosis, the overall clinical management remains suboptimal [2]. Obstructive sleep apnoea (OSA) is the most common type of sleep-disordered breathing. It is characterised by recurrent episodes of either partial or complete upper airway obstruction during sleep, which leads to episodes of interruption of respiration associated with fragmented sleep and intermittent hypoxia [3]. According to different diagnostic methods, the incidence of OSA in the general population is approximately 4%-32.9% [4]. However, the incidence of OSA in HCM is up to 32%-71% [3]. A previous study reported that untreated OSA can decrease excise capacity [5], increase the risk of atrial fibrillation (AF), and enlarge the ascending aorta diameter in HCM [6]. Notably, the presence of OSA in patients with HOCM could be an important contributor to drug-refractory symptoms and worsening LVOTO. Moreover, the presence of OSA could predispose the patient to increased arrhythmias and tachycardia, and finally contribute to sudden death, as a result of heightened sympathetic activity [2,7]. A recent study found that acute application of continuous positive airway pressure (CPAP) is safe in patients with HCM [8]. Further understanding the relationship between these two conditions can promote a better prognosis of HOCM. To our knowledge, no study has reported an association between septal myectomy and OSA in patients with HOCM. Therefore, in this study, we aimed to determine the incidence of OSA in patients with HOCM and elucidate the association between septal myectomy and OSA before and 3 months after surgery.
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Materials and Methods
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Patients
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We included 85 consecutive patients with HOCM evaluated at Fuwai Hospital in Beijing between September 2017 and March 2018. The diagnostic criteria of HOCM and surgical indications were consistent with the 2011 American Heart Association/American College of Cardiology guideline and the 2014 European Society of Cardiology guideline, which mainly include an unexplained septal hypertrophy with a thickness of >15 mm. Latent LVOTO is defined as an instantaneous peak Doppler left ventricular outflow tract pressure gradient <30 mmHg at rest, while during physiological provocation, such as Valsalva manoeuvre, standing, and exercise, the left ventricular outflow tract pressure gradient is 30 mmHg [1,9]. All patients underwent polysomnography
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(PSG) before and 3 months after surgery. Demographic and clinical data of the patients were collected during the hospital stay and 3 months after surgery. The study was approved by the ethics committees of Fuwai Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained from all patients, in accordance with the principles of the Declaration of Helsinki.
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Echocardiography
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Echocardiographic examinations were performed by one experienced physician. Cardiac chamber diameters were expressed as the maximum value of the anteroposterior diameter in cardiac cycles. The diameter of the ascending aorta was approximately 4 cm above the aortic valve during diastole. The thicknesses of the interventricular septum (IVS) and ventricular wall were determined during diastole. Aside from maximum thickness, the representative thickness of the IVS, which is usually the thickness of the point 25 mm under the right coronary sinus nadir, was also recorded to indicate overall thickness. Left ventricular outflow tract gradient was calculated using the simplified Bernoulli equation. The measurements of left ventricular (LV) ejection fraction were determined by following the American Society of Echocardiography recommendations. More detailed methods are provided in our previous publication [10].
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Cardiac Surgery
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As described previously [11], we performed an extended Morrow procedure. The hypertrophic ventricular septum resulting in systolic anterior motion of the mitral valve and LVOTO was resected. The resection ranges were as follows: in the long axis, the myectomy started from approximately 4 mm below the aortic ring to the apex of the left ventricle; in the short axis, the myectomy started rightward to the nadir of the right aortic cusp and terminated near the mitral anterior commissure. Hypertrophy of the LV anterior free wall leading to left ventricular outflow tract (LVOT) narrowing may also need resection. Furthermore, the anomalous chordal attachments
Figure 1 Flow diagram of study patients.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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affecting the LVOT were also excised. If intra-operative transoesophageal echocardiography detected a postoperative LVOT gradient >30 mmHg or more than mild-to-moderate mitral valve regurgitation after weaning from cardiopulmonary bypass, re-operation was required. Concomitant surgery was performed based on expert consensus among the experienced cardiac surgeons.
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Polysomnography
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Polysomnography was performed in all participants using standard PSG techniques (Embletta; Embla, Woodbridge,
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UK) before and 3 months after surgery. This investigation consisted of monitoring of the electroencephalogram, electrooculogram, submental electromyogram, electrocardiogram, thoraco-abdominal excursions, oronasal airflow by an airflow pressure transducer, and arterial oxygen saturation by pulse oximetry. Obstructive apnoea was defined as the absence of oronasal airflow for at least 10 s in the presence of out-of-phase thoracoabdominal effort. Hypopnoea was defined as a 50% reduction in oronasal airflow for 10 s associated with a 3% decrease in oxygen saturation. The apnoea–hypopnoea index (AHI) was calculated as the mean
Table 1 Baseline characteristics of the study population. Variable
Total (n = 85)
No OSA (n = 36)
OSA (n = 49)
p
Age (y)
48.6 11.7
42.86 10.8
52.5 10.8
<0.001
BMI (kg/m2)
25.4 3.1
24.9 3.30
25.72 2.96
0.395
Male
54 (63)
24 (67)
30 (61)
0.607
HR (bpm)
70.0 (65.0-75.0)
70.0 (64.2-74.5)
72.0 (64.7-75.0)
0.298
Course of disease (y)
4.0 (1.0-6.0)
3.4 (0.0-5.0)
4.0 (2.0-7.50)
0.059
NYHA class
2.6 0.6
2.6 0.6
2.6 0.5
0.765
Family history of HCM or SCD
19 (22)
13 (36)
6 (12)
0.009
Beta blockers Calcium channel antagonist
79 (93) 8 (9)
34 (94) 3 (8)
45 (92) 5 (10)
0.643 1.000
Chest pain
21 (25)
10 (28)
11 (22)
0.574
Amaurosis
8 (9)
1 (3)
7 (14)
0.156
Syncope
13 (16.5)
2 (6)
11 (24.4)
0.042
Chest distress
57 (67)
23 (64)
34 (69)
0.594
Glucose (mmol/L)
4.5 (4.2-4.8)
4.2 (4.0-4.6)
4.6 (4.3-5.1)
0.005
hs-CRP (mg/L)
1.1 (0.4-1.5)
1.0 (0.6-1.3)
1.1 (0.3-2.3)
0.816
BNP (pg/mL) Endothelin (pmol/L)
1546.0 (840.1-2504.5) 0.4 (0.2-0.5)
1688.0 (1373.0-2608.0) 0.2 (0.1-0.3)
1464.5 (557.8-2701.5) 0.5 (0.4-0.7)
0.223 0.003
SaO2
95.7 (94.3-96.3)
96.0 (95.1-96.4)
95.4 (93.1-96.1)
0.045
LAD (mm)
45.90 6.33
44.93 6.88
46.56 5.91
0.319
IVST (mm)
22.57 4.26
24.64 4.38
21.15 3.57
0.001
LVEF (%)
70.0 (64.0-75.0)
72.0 (62.0-75.0)
70.0 (65.0-75.0)
0.464
LVEDD (mm)
42.0 (38.0-45.0)
39.0 (37.0-42.0)
43.5 (39.0-46.0)
0.001
RAD (mm)
21.0 (20.0-22.8)
21.0 (20.0-23.0)
21.0 (18.0-24.0)
0.330
LVPWT (mm) LVOTG (mmHg)
11.5 (10.0-13.8) 77.3 25.1
11.0 (10.0-13.0) 77.3 29.1
12.0 (10.0-14.0) 85.8 26.3
0.119 0.225
Ascending aorta diameter (mm)
31.0 (29.0-34.0)
30.0 (27.5-32.0)
32.0 (30.0-35.0)
0.044
Moderate or severe MR
46 (66.7)
11 (39.3%)
35 (85.4)
<0.001
AF
11 (13)
1 (3)
10 (20)
0.039
MVO
19 (22)
13 (36)
6 (12)
0.009
RVOTO
2 (2)
0 (0)
2 (4)
0.135
Myocardial bridge
26 (31)
13 (36)
13 (26)
0.344
Latent LVOTO Pulmonary hypertension
17 (20) 8 (9)
12 (33) 0 (0)
5 (10) 8 (16)
0.008 0.018
Data are n (%), mean standard deviation, or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; BMI, body mass index; HR, heart rate; bpm, beats per min; NYHA, New York Heart Association; HCM, Q4
hypertrophic cardiomyopathy; SCD,? ??; hs-CRP, high-sensitivity C-reactive protein; BNP, brain natriuretic peptide; LAD, left atrial diameter; IVST, interventricular septal thickness; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; RAD, right atrial diameter; LVPWT, left ventricular posterior wall thickness; LVOTG, left ventricular outflow tract gradient; MR, mitral regurgitation; AF, atrial fibrillation; MVO, middle ventricular obstruction; RVOTO, right ventricular outflow tract obstruction; LVOTO, left ventricular outflow tract obstruction.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 2 Preoperative polysomnography parameters.
Q5
Variable
No OSA (n = 36)
OSA (n = 49)
p
AHI (1/h) Longest apnoea and hypopnoea time (s)
1.0 (0.2-1.9) 24.4 (19.7-42.6)
12.4 (7.20-22.2) 71.6 (55.2-94.3)
<0.001 <0.001
OAI (1/h)
0.8 (0.3-1.9)
11.3 (6.6-21.4)
<0.001
CAI (1/h)
0.0 (0.0-0.1)
0.3 (0.0-1.5)
0.001
Hypopnoea index (1/h)
0.6 (0.1-1.7)
2.6 (0.4-5.2)
<0.001
Lowest PO2 (%)
88.0 (82.5-90.0)
81.0 (75.0-86.0)
0.002
Snoring time ratio (%)
4.3 (0.6-8.9)
8.7 (3.2-15.1)
0.020
Mean PO2 (%)
94.5 (92.9-95.5)
89.7 (87.6-90.7)
<0.001
ODI (1/h) Mean PO2 decline degree (%)
3.21 3.35 4.48 1.02
15.83 13.87 5.87 1.81
<0.001 <0.001
Total sleep time <90% SpO2
0.1 (0.0-4.5)
8.4 (1.3-16.5)
<0.001
Supine time (min)
252.00 106.40
269.30 108.61
0.896
Total sleep time (min)
533.0 (507.3-575.4)
529.0 (492.0-578.6)
0.922
Data are mean standard deviation or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; AHI, apnoea–hypopnoea index; OAI, obstructive apnoea index; CAI, central apnoea index; ODI, oxygen desaturation index.
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number of apnoeas and hypopnoeas per hour of sleep. If the AHI is >5, it is defined as the OSA group.
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Statistical Analysis
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The Kolmogorov–Smirnov test was used to assess normal distribution of continuous variables. The results were expressed as mean standard deviation (SD), median (interquartile range [IQR]), or percentage, when appropriate. The Student’s t-test for independent samples and the Mann–Whitney U-test were used to compare continuous variables as appropriate, and the x2 or Fisher’s exact test were used to compare nominal variables as appropriate. Spearman correlation analysis was performed to estimate the correlations between polysomnography parameters and glucose or left ventricular end-diastolic diameter (LVEDD) or interventricular septum thickness and between the DAHI and other parameters. Multivariate linear regression models were performed for DAHI. Variables with a p-value <0.1 on univariate analysis were entered into a multivariate analysis. All reported probability values were two-tailed, and a p-value <0.05 was considered statistically significant. SPSS version 24.0 statistical software (IBM) and GraphPad Prism 7.0 (GraphPad Software, La Jolla, CA, USA) were used for calculations and illustrations, respectively.
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Results
150
Baseline Patient Characteristics
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We enrolled 85 patients who underwent septal myectomy (Figure 1). The baseline characteristics of the entire population, as well as subgroups according to the absence or
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presence of OSA, are described in Table 1. Obstructive sleep apnoea was present in 49 patients (58%). Patients with OSA were older. Compared with patients without OSA, patients with OSA had an enlarged ascending aorta (median, 32.0 [IQR, 30.0-35.0] vs 30.0 [IQR, 27.5-32.0]; p = 0.044) and LVEDD (median, 43.5 [IQR, 39.0-46.0] vs 39.0 [IQR, 37.042.0]; p = 0.001). Nevertheless, patients without OSA had relatively thicker interventricular septal thickness (IVST) (mean SD, 24.64 4.38 vs 21.15 3.57; p = 0.001). In addition, the prevalence of AF (20.4% vs 2.8%; p = 0.039) and pulmonary hypertension (16.3% vs 0%; p = 0.018) were significantly higher in patients with OSA. The prevalence of middle ventricular obstruction (12.2% vs 36.1%; p = 0.009) and latent LVOTO (10.2% vs 33.3%; p = 0.008) were significantly higher in patients without OSA.
Preoperative Polysomnography Parameters Preoperative sleep study parameters are summarized in Table 2. Compared with patients without OSA, almost all PSG parameters, including AHI, obstructive apnoea index (OAI), central apnoea index (CAI), hypopnoea index (HI), lowest pO2, oxygen desaturation index, mean pO2, and snoring time ratio, were significantly altered. However, no difference was noted in total sleep time between the two groups. In addition, a strong correlation of lowest oxygen saturation (rs=–0.328, p = 0.037), snoring time ratio (rs = 0.499, p = 0.001), and total sleep time <90% SpO2 (rs = 0.347, p = 0.026) with LVEDD was found in patients with OSA, and not AHI, OAI, or HI. A correlation was also noted between oxygen desaturation index and plasma glucose levels (rs = 0.318, p = 0.049) and enlarged
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 3 Perioperative clinical data. Variable
No OSA (n = 36)
OSA (n = 49)
p
Duration of CPB (min) Aortic cross-clamp time (min)
89.5 (79.0-120.0) 58.5 (51.3-80.8)
98.0 (79.0-147.5) 59.0 (47.0-97.5)
0.328 0.912
Duration of postoperative ventilation (h)
18.0 (15.0-21.8)
18.5 (16.0-24.0)
0.160
Length of ICU stay (h)
48.0 (28.3-72.0)
48.0 (24.0-85.5)
0.845
Weight of resected myocardium (g)
10.65 4.76
9.01 3.12
0.006
Postoperative AF
4 (11)
15 (31)
0.03
Postoperative LVEF (%)
61.0 (60.0-65.0)
60.0 (60.0-63.8)
0.465
Septal myectomy alone
25 (69)
32 (65)
0.688
CABG Double valve replacement
0 (0) 0 (0)
2 (4) 1 (2)
0.506 1.000
Mitral valve replacement
0 (0)
2 (4)
0.506
Mitral valvuloplasty
8 (22)
9 (18)
0.661
Maze procedure
1 (3)
4 (8)
0.297
Coronary myocardial bridge unroofing
3 (8)
5 (10)
0.770
Length of postoperative hospital (d)
7.0 (7.0-8.0)
7.0 (7.0-9.5)
0.427
WPW pathway amputation
2 (6)
0 (0)
0.176
Pacemaker implantation
0 (0)
4 (8)
0.134
Data are n (%), mean standard deviation, or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; CBP, cardiopulmonary bypass; ICU, intensive care unit; AF, atrial fibrillation; LVEF, left ventricular ejection fraction; CABG, coronary artery bypass grafting; WPW, Wolff–Parkinson–White syndrome.
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ascending aorta (rs = 0.401, p = 0.009). In addition, no patient underwent CPAP treatment before operation.
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Effect of Obstructive Sleep Apnoea on the Perioperative Period
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The effects of OSA on perioperative period are summarised in Table 3. The incidence of AF was significantly higher (11.1% vs 30.6%; p = 0.033) and the weight of resection myocardium was lower (9.01 3.12 vs 10.65 4.76; p = 0.006) in patients with OSA than those in patients without OSA.
However, no difference was found between the two groups of patients in terms of cardiopulmonary bypass time, aortic cross-clamp time, intensive care unit stay time, and concomitant operation (Table 3).
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Clinical Parameters Before and 3 Months After Septal Myectomy
197
As shown in Table 4, there was no significant change in body mass index before and after surgery in the two groups. Overall, compared to the preoperative data, left ventricular
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Table 4 Clinical parameters before and 3 months after septal myectomy. Variables
Patients with OSA Preoperative
Patients without OSA Postoperative
Preoperative
Postoperative
pa
BMI (kg/m2)
25.7 2.96
25.5 2.66
24.9 3.29
24.8 3.13
0.21
LVOTG (mmHg)
85.8 26.3
13.3 7.6b
77.3 29.1
9.4 4.4b
0.009
NYHA class
2.6 0.6
1.2 0.5b
2.6 0.5
1.1 0.4b
0.387
Use of pain or sleeping medications
–
–
0 (0%)
0 (0%)
1.00
Moderate or severe MR (%)
35 (85)
3 (7)b
11 (39)
2 (7)b
0.978
IVST (mm)
21.15 3.57
13.3 2.6
24.64 4.38
14.3 3.8b
0.254
b
Data are n (%) or mean standard deviation. *p < 0.05, preoperative vs postoperative. Abbreviations: OSA, obstructive sleep apnoea; BMI, body mass index; LVOTG, left ventricular outflow tract gradient; NYHA, New York Heart Association; MR, mitral regurgitation; IVST, interventricular septal thickness. a
Patients with and without OSA postoperatively.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 5 Effects of septal myectomy on obstructive sleep apnoea (OSA). Variable
Patients with OSA Preoperative
Q8
Patients without OSA Postoperative
p
Preoperative
Postoperative
p
AHI (1/h)
11.7 (7.2-22.1)
25.6 (17.7-33.8)
<0.001
1.0 (0.2-1.9)
1.9 (0.8-3.3)
0.079
Mix index (1/h)
0.0 (0.0-0.35)
0.1 (0.0-1.4)
0.915
0 (0-0)
0 (0-0)
0.915
OAI (1/h) CAI (1/h)
11.6 (6.8-17.6) 0.4 (0.0-2.1)
15.1 (9.5-20.8) 0.2 (0.0-0.8)
0.024 0.008
0.8 (0.3-1.9) 0.0 (0.0-0.1)
0.5 (0.1-1.1) 0.0 (0.0-0.1)
0.210 0.232
HI (1/h)
4.4 (2.5-7.1)
8.3 (4.1-12.0)
0.003
0.6 (0.1-1.7)
1.3 (0.5-2.3)
0.141
Lowest PO2 (%)
81.0 (74.5-86.0)
80.0 (70.5-84.0)
0.251
88.0 (82.5-90.0)
84.0 (78.0-89.0)
0.318
Snoring time ratio (%)
8.7 (3.2-15.1)
12.6 (3.1-22.5)
0.003
4.3 (0.6-9.0)
6.8 (0.4-10.5)
0.187
Mean PO2 (%)
89.7 (87.2-90.8)
93 (90.1-94.0)
0.001
94.5 (92.9-95.5)
92.1 3.0
0.050
ODI (1/h)
15.8 13.9
20.6 16.3
0.016
3.2 3.4
5.2 5.6
0.124
Mean PO2 decline degree (%)
5.9 1.8
6.3 1.9
0.008
4.5 1.0
4.6 (4.4-5.3)
0.442
Total sleep time <90% SpO2 Supine time (min)
8.4 (1.3-16.5) 269.3 108.6
8.7 (1.5-23.8) 252.2 123.2
0.476 0.247
0.1 (0.0-4.5) 252.0 106.4
3.1 (0.0-37.8) 195.9 101.9
0.150 0.044
Total sleep time (min)
529.0 (492.0-578.6)
525.9 (490.1-573.1)
0.124
533.0 (507.3-575.4)
540.4 (502.2-571.0)
0.891
Data are mean standard deviation or median (interquartile range). Abbreviations: AHI, apnoea hypoxia index; OAI, obstructive apnoea index; CAI, central apnoea index; HI, hypopnoea index; ODI, oxygen desaturation index.
202 203 204 205 206 Q17 207 208 209 210 211 212 213 214 215 216 217 218
outflow tract gradient (LVOTG), New York Heart Association class, IVST, and the percentages of moderate or severe mitral regurgitation were significantly improved. However, compared to patients without OSA, patients with OSA had a relatively higher LVOTG after surgery (13.3 7.6 vs 9.4 4.4; p = 0.009).
Changes in Polysomnography Parameters Before and After Surgery We studied the changes in the parameters pre- and postoperatively. We found no changes in patients without OSA. However, the AHI, OAI, and HI were significantly increased in almost all patients with OSA (median, 11.7 [IQR, 7.2-22.1] vs 25.6 [IQR, 17.7-33.8] [p < 0.001]; median, 11.6 [IQR, 6.817.6] vs 15.1 [9.5-20.8] [p=0.024]; and median, 4.4 [IQR, 2.57.1] vs 8.3 [IQR, 4.1-12.0] [p=0.003], respectively), whereas the CAI decreased (median, 0.4 [IQR, 0.0-2.1] vs 0.2 [0.0-0.8]; p=0.008) (Table 5, Figure 2). This result indicates that the
severity of OSA increased significantly after surgery. To further study the cause of the aggravation of OSA, stepwise multiple linear regression demonstrated that mean oxygen saturation and time% with SpO2 <90% were the only variables associated with DAHI (p = 0.026 and p = 0.007, respectively; adjusted R2 = 0.365) (Table 6). In addition, not all patients were treated with CPAP during hospitalisation and after discharge.
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Discussion
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To our knowledge, this study is the first to investigate systematically the relationship between HOCM and OSA in patients undergoing septal myectomy. The main findings are as follows. Firstly, the incidence of OSA in patients with HOCM was up to 58%. Secondly, OSA was associated with higher AF incidence during the perioperative period of septal myectomy. Thirdly, the severity of OSA significantly
228
Figure 2 Changes in apnoea–hypopnea index (AHI) before and after septal myectomy in patients with and without obstructive sleep apnoea.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 6 Multiple linear regression between delta apnoea–hyopnoea index with significant variables from Spearman analysis. Variable
Multivariate adjusted R2 = 0.365
Univariate r
p
B
p
LA
0.419
0.006
0.279
0.064
BMI
0.477
0.444
0.229
0.104
Age
–0.055
0.746
–0.097
0.493
Sex Cardiothoracic ratio
0.423 0.267
0.910 0.092
–0.138 0.117
0.361 0.427
Supine sleep time (min)
–0.356
0.022
0.096
0.526
Oxygen partial pressure
–0.295
0.081
0.047
0.758
Oxygen saturation
–0.279
0.099
–0.013
0.933
PAD (mm)
0.321
0.044
0.016
0.916
Nocturnal mean oxygen saturation
–0.309
0.050
0.159
0.026
Total sleep time <90% SpO2
0.343
0.028
0.159
0.007
Abbreviations: LA, left atrium; BMI, body mass index; PAD = pulmonary artery diameter.
235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269
increased 3 months after septal myectomy, as determined by AHI, OAI, and HI. Finally, the mean oxygen saturation and time% with SpO2 <90% during sleep before surgery were independently associated with the aggravation of OSA after the surgery. Previous studies indicate a high prevalence of OSA in patients with HCM, ranging from 32% to 71% [3]. In the present study, the prevalence of OSA in HCM was consistent with previous studies [5,6,12]. OSA may affect HOCM through multiple mechanisms, including activation of the sympathetic nervous system, increase in heart rate, insulin resistance, and myocardial wall stress, depression of parasympathetic activity, and impairment of vascular endothelial function [13]. Our data showed no difference in heart rate, blood pressure, or plasma catecholamine between patients with and without OSA. However, the levels of plasma glucose and endothelin were significantly higher in patients with OSA. These results indicate that insulin resistance and endothelial dysfunction exist in patients with HOCM complicated by OSA. In the present study, the prevalence of AF in patients with OSA was significantly high. This is consistent with a previous study, which found that the presence and severity of sleepdisordered breathing may influence left atrial volume index and the prevalence of AF in patients with HCM [14]. Intrathoracic pressure shifts, sympathovagal imbalance, and atrial remodelling induced by OSA may play an important role in AF in patients with HCM [15]. Furthermore, the diameter of the aorta and the prevalence of pulmonary hypertension were significantly high in patients with OSA, and a high proportion of latent LVOTO was noted. During OSA, futile inspiratory efforts against the occluded pharynx cause abrupt reductions in intrathoracic negative pressure. On the one hand, this increases left ventricular transmural pressure, and hence the afterload also increases [16]. On the other
hand, venous return is also enhanced, resulting in right ventricular distension and a leftward shift of the IVS [17]. All these mechanisms can aggravate LVOTO and mitral regurgitation. Pulmonary venous hypertension due to LV systolic and diastolic dysfunction is currently speculated to be the most common form of pulmonary hypertension in patients with OSA [18]. However, no difference was found in left atrium diameter between patients with and without OSA. This result may be attributed to the fact that our patients were relatively young. In addition, we found significant correlations between LVEDD and lowest oxygen saturation, snoring time ratio, and total sleep time <90% SpO2, which is the marker for disease severity in HCM [19]. Recurrent activation of the sympathetic system due to oxygen desaturation during sleep apnoea may contribute to the development of HOCM. Prior studies reported that AHI significantly increases after non-cardiac surgery, and that even a few patients without OSA before surgery may develop after it. In these studies, the type of surgery included spinal, orthopaedic, and gynaecological; no patients underwent cardiac surgery. Moreover, general anaesthesia has no effect on postoperative AHI elevation [20,21]. Some studies also found that OSA is independently associated with a higher rate of new cardiovascular events in the long-term follow-up of patients who underwent coronary artery bypass grafting and is an independent predictor of postoperative AF in cardiac surgery [22,23]. In addition, some cardiovascular disease mechanisms exist, including nocturnal rostral fluid shift and less excise, which aggravate the development of OSA [6,24]. The higher prevalence of AF after the surgery in the present study is in accordance with these previous studies. A recent study found that valve repair improves central sleep apnoea, while there was no influence on OSA [25]. However, data on the severity of OSA after septal myectomy are not available to
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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date. Moreover, almost all patients can return to normal life 3 months after surgery, the effects of anaesthesia and sternotomy are eliminated. Therefore, we chose 3 months after surgery as the observation end point, and some patients underwent PSG 6 months after surgery. In our study, in the case of no change in body mass index, we found that AHI, OAI, and HI were significantly increased 3 months after septal myectomy, and a few patients without OSA before surgery may develop after it. This finding is inconsistent with the results obtained in a previous study, which reported that percutaneous transluminal septal myocardial ablation significantly decreases the AHI [26]. Similarly, in patients with severe aortic stenosis and valve regurgitation, a significant improvement in central sleep apnoea (CSA) is noted after transcatheter aortic valve implantation and valve repair [25,27]. There may be several explanations for this. Firstly, in these studies, most of the patients were elderly and had heart failure. Secondly, the method used was cardiopulmonary polygraphy instead of a standard PSG. Thirdly, the decrease in AHI in their research was mainly due to the decline of the CAI, and the type of preoperative sleep apnoea was mainly CSA. A prior study demonstrated that the upper airway changes from a more transversely oriented elliptical shape when supine to a more circular shape when in the lateral recumbent posture, and increased circularity decreases the propensity for tube collapse and may account for the postural dependency of OSA [28]. However, in our patients, no difference was noted in the supine sleeping time before and after the surgery. In multiple linear regression analysis, we found that the mean oxygen saturation and time % with SpO2 <90% during sleep before surgery were independently associated with the aggravation of OSA postoperatively. The night-to-night variability in the frequency of sleep apnoea and hypopnoea and the changes in sleep structure may have contributed to this result [21]. However, the specific mechanism for this is unknown and requires further investigation; it is not clear whether this phenomenon exists in other cardiac surgery patients. In patients with coronary artery disease, timely diagnosis and treatment in those undergoing PCI can serve as a clinically relevant method of secondary prevention to decrease the risk of repeat revascularisation in patients with coronary disease. Importantly, a recent study found that after CPAP treatment in patients with HOCM and OSA, a marked improvement in symptoms and a reduction in LVOTG abrogate the need for septal reduction [2,29]. In the present study, septal myectomy significantly improved the symptoms, cardiac function, and relief of LVOTO. However, when compared with patients without OSA, the postoperative LVOTG was significantly higher in patients with OSA. Therefore, we believe that early diagnosis and timely administration of CPAP treatment should improve the long-term effect of surgery in these patients. The present study has some limitations. Firstly, the sample size was relatively small. We did not include patients with CSA. Therefore, further studies with a larger population are needed to confirm the results. Secondly, we did not monitor
the sleep structure of the patients. Previous studies showed that changes in sleep structure may affect the occurrence and severity of sleep apnoea [21]. Thirdly, a relatively short follow-up period may limit the understanding of long-term postoperative outcomes in patients with HOCM and OSA. In conclusion, OSA is highly prevalent in patients with HOCM and can increase the incidence of perioperative AF of septal myectomy. In addition, the severity of OSA significantly increased 3 months after the operation. The mean oxygen saturation and time% with SpO2 <90% during sleep before operation were independently associated with the increase of AHI. The specific mechanism of such deterioration of OSA after septal myectomy needs to be determined in detail. Long-term follow-up is also necessary to evaluate the dynamic changes of OSA after resolution of the obstruction in patients with HOCM.
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Conflict of Interest
378
There are no conflicts of interest to disclose.
379
Funding Sources
380
This work was supported by the National Natural Science Foundation of China (grant number: 81570276).
References [1] American College of Cardiology Foundation/American Heart Association Task Force on Practice, American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society. et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg 2011;142: e153–203. [2] Sengupta PP, Sorajja D, Eleid MF, Somers VK, Ommen SR, Parish JM, et al. Hypertrophic obstructive cardiomyopathy and sleep-disordered breathing: an unfavorable combination. Nat Clin Pract Cardiovasc Med 2009;6:14–5. [3] Nerbass FB, Pedrosa RP, Danzi-Soares NJ, Drager LF, Arteaga-Fernandez E, Lorenzi-Filho G. Obstructive sleep apnea and hypertrophic cardiomyopathy: a common and potential harmful combination. Sleep Med Rev 2013;17:201–6. [4] Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217–39. [5] Konecny T, Geske JB, Ludka O, Orban M, Brady PA, Abudiab MM, et al. Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy. Chest 2015;147:1574–81. [6] Pedrosa RP, Drager LF, Genta PR, Amaro AC, Antunes MO, Matsumoto AY, et al. Obstructive sleep apnea is common and independently associated with atrial fibrillation in patients with hypertrophic cardiomyopathy. Chest 2010;137:1078–84. [7] Saurabh Aggarwal MFJ, Agarwa Anushree. Hypertrophic cardiomyopathyassociated with sleep apnea:serious implications andcogent management strategy. Expert Rev Cardiovasc Ther 2015;13:277–84. [8] Nerbass FB, Salemi VMC, Pedrosa RP, Portilho NP, Ferreira-Filho JCA, Moriya HT, et al. Acute effects of nasal CPAP in patients with hypertrophic cardiomyopathy. Chest 2016;150:1050–8. [9] Authors/Task Force members, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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[10]
[11]
[12]
[13] [14]
[15]
[16]
[17]
[18]
[19]
Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733–79. Wang J, Sun X, Xiao M, Zhang M, Chen H, Zhu C, et al. Regional left ventricular reverse remodeling after myectomy in hypertrophic cardiomyopathy. Ann Thorac Surg 2016;102:124–31. Wang S, Cui H, Yu Q, Chen H, Zhu C, Wang J, et al. Excision of anomalous muscle bundles as an important addition to extended septal myectomy for treatment of left ventricular outflow tract obstruction. J Thorac Cardiovasc Surg 2016;152:461–8. Eleid MF, Konecny T, Orban M, Sengupta PP, Somers VK, Parish JM, et al. High prevalence of abnormal nocturnal oximetry in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:1805–9. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82–93. Konecny T, Brady PA, Orban M, Lin G, Pressman GS, Lehar F, et al. Interactions between sleep disordered breathing and atrial fibrillation in patients with hypertrophic cardiomyopathy. Am J Cardiol 2010;105: 1597–1602. Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: pathophysiological mechanisms and therapeutic implications. Int J Cardiol 2017;230:293–300. Bradley TD, Hall MJ, Ando S, Floras JS. Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure. Chest 2001;119:1827–35. Brinker JA, Weiss JL, Lappe DL, Rabson JL, Summer WR, Permutt S, et al. Leftward septal displacement during right ventricular loading in man. Circulation 1980;61:626–33. Kholdani C, Fares WH, Mohsenin V. Pulmonary hypertension in obstructive sleep apnea: is it clinically significant? A critical analysis of the association and pathophysiology. Pulm Circ 2015;5:220–7. Maron BJ, Olivotto I, Spirito P, Casey SA, Bellone P, Gohman TE, et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non–referral-based patient population. Circulation 2000;102:858–64.
[20] Chung F, Liao P, Yang Y, Andrawes M, Kang W, Mokhlesi B, et al. Postoperative sleep-disordered breathing in patients without preoperative sleep apnea. Anesth Analg 2015;120:1214–24. [21] Chung F, Liao P, Elsaid H, Shapiro CM, Kang W. Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology 2014;120:299–311. [22] Wong JK, Maxwell BG, Kushida CA, Sainani KL, Lobato RL, Woo YJ, et al. Obstructive sleep apnea is an independent predictor of postoperative atrial fibrillation in cardiac surgery. J Cardiothorac Vasc Anesth 2015;29:1140–7. [23] Uchoa CHG, Danzi-Soares NJ, Nunes FS, de Souza AAL, Nerbass FB, Pedrosa RP, et al. Impact of OSA on cardiovascular events after coronary artery bypass surgery. Chest 2015;147:1352–60. [24] Yumino D, Redolfi S, Ruttanaumpawan P, Su MC, Smith S, Newton GE, et al. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation 2010;121:1598–605. [25] Abe H, Takahashi M, Yaegashi H, Eda S, Kitahara H, Tsunemoto H, et al. Valve repair improves central sleep apnea in heart failure patients with valvular heart diseases. Circ J 2009;73:2148–53. [26] Akita K, Maekawa Y, Kohno T, Tsuruta H, Murata M, Fukuda K. Ameliorating the severity of sleep-disordered breathing concomitant with heart failure status after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy. Heart Vessels 2017;32:1320–6. [27] Linhart M, Pabst S, Fistera R, Ghanem A, Sinning JM, Hammerstingl C, et al. Transcatheter valve implantation improves central sleep apnoea in severe aortic stenosis. Eurointervention 2013;9:923–8. [28] Walsh JH, Leigh MS, Paduch A, Maddison KJ, Armstrong JJ, Sampson DD, et al. Effect of body posture on pharyngeal shape and size in adults with and without obstructive sleep apnea. Sleep 2008;31:1543–9. [29] Wu X, Lv S, Yu X, Yao L, Mokhlesi B, Wei Y. Treatment of OSA reduces the risk of repeat revascularization after percutaneous coronary intervention. Chest 2015;147:708–18.
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ORIGINAL ARTICLE
Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy [TD$FIRSNAME]Shengwei[TD$FIRSNAME.] [TD$SURNAME]Wang[,TD$SURNAME.] MD a*, [TD$FIRSNAME]Hao[TD$FIRSNAME.] [TD$SURNAME]Cui[TD$SURNAME.], MD b, [TD$FIRSNAME]Liukun[TD$FIRSNAME.] [TD$SURNAME]Meng[TD$SURNAME.], MD a, [TD$FIRSNAME]Rong[TD$FIRSNAME.] [TD$SURNAME]Wu[TD$SURNAME.], MD a, [TD$FIRSNAME]Bing[TD$FIRSNAME.] [TD$SURNAME]Tang[TD$SURNAME.], MD a, [TD$FIRSNAME]Changsheng[TD$FIRSNAME.] [TD$SURNAME]Zhu[TD$SURNAME.], MD a, [TD$FIRSNAME]Qinjun[TD$FIRSNAME.] [TD$SURNAME]Yu[TD$SURNAME.], MD a, [TD$FIRSNAME]Xiaohong[TD$FIRSNAME.] [TD$SURNAME]Huang[TD$SURNAME.], MD c, [TD$FIRSNAME]Shuiyun[TD$FIRSNAME.] [TD$SURNAME]Wang[TD$SURNAME.], MD a a
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China b Q11 Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA c Department of Special Medical Treatment Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Received 22 January 2019; accepted 23 May 2019; online published-ahead-of-print xxx
Background
The prevalence of obstructive sleep apnoea (OSA) is high in patients with hypertrophic cardiomyopathy. The effect of septal myectomy on OSA is not clear. This study aimed to examine the association between hypertrophic obstructive cardiomyopathy and OSA before and after septal myectomy.
Method
We included 85 consecutive patents with a confirmed diagnosis of hypertrophic obstructive cardiomyopathy who underwent septal myectomy. Polysomnography was performed in all patients before and 3 months after the surgery.
Results
Of the 85 patients, 49 (58%) were diagnosed with OSA. Patients with OSA were significantly older than those without OSA. The incidence of atrial fibrillation significantly increased during perioperative period in patients with OSA (p = 0.03). The severity of OSA significantly increased 3 months after surgery, as determined by the apnoea–hypopnea index (AHI; p < 0.001), obstructive apnoea index (p = 0.024), and hypopnoea index (p = 0.003), whereas central apnoea index was decreased (p = 0.008). In the multivariate linear regression analysis, mean oxygen desaturation and time% with SpO2 <90% during sleep before surgery were significantly associated with increased AHI, independently of body mass index and sex (p = 0.026 and p = 0.007, respectively; adjusted R2 = 0.365).
Conclusions
The severity of OSA significantly increased 3 months after septal myectomy as determined by AHI, obstructive apnoea index, and hypopnoea index. Mean oxygen saturation and time% with SpO2 <90% during sleep before surgery were independently associated with the increase of AHI. However, the specific mechanism of such deterioration of OSA after septal myectomy needs to be determined in detail.
Keywords
Obstructive sleep apnea Septal myectomy Hypertrophic cardiomyopathy Atrial fibrillation Sleep disorder Polysomnography
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*Corresponding author at: 167 Beilishi Road, Xicheng District, Beijing 100037, China. Tel./ fax: +86-10-88396636/+86-10-68330739., Email: [email protected] © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Introduction
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S. Wang et al.
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Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease, with a prevalence of approximately 1:500 in the general population. About two-thirds of patients with HCM have left ventricular outflow tract obstruction (LVOTO). If the symptoms of these patients are refractory to optimal pharmacological therapy, septal myectomy is recommended [1]. Although the surgical treatment of hypertrophic obstructive cardiomyopathy (HOCM) has a good prognosis, the overall clinical management remains suboptimal [2]. Obstructive sleep apnoea (OSA) is the most common type of sleep-disordered breathing. It is characterised by recurrent episodes of either partial or complete upper airway obstruction during sleep, which leads to episodes of interruption of respiration associated with fragmented sleep and intermittent hypoxia [3]. According to different diagnostic methods, the incidence of OSA in the general population is approximately 4%-32.9% [4]. However, the incidence of OSA in HCM is up to 32%-71% [3]. A previous study reported that untreated OSA can decrease excise capacity [5], increase the risk of atrial fibrillation (AF), and enlarge the ascending aorta diameter in HCM [6]. Notably, the presence of OSA in patients with HOCM could be an important contributor to drug-refractory symptoms and worsening LVOTO. Moreover, the presence of OSA could predispose the patient to increased arrhythmias and tachycardia, and finally contribute to sudden death, as a result of heightened sympathetic activity [2,7]. A recent study found that acute application of continuous positive airway pressure (CPAP) is safe in patients with HCM [8]. Further understanding the relationship between these two conditions can promote a better prognosis of HOCM. To our knowledge, no study has reported an association between septal myectomy and OSA in patients with HOCM. Therefore, in this study, we aimed to determine the incidence of OSA in patients with HOCM and elucidate the association between septal myectomy and OSA before and 3 months after surgery.
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Materials and Methods
56
Patients
57
We included 85 consecutive patients with HOCM evaluated at Fuwai Hospital in Beijing between September 2017 and March 2018. The diagnostic criteria of HOCM and surgical indications were consistent with the 2011 American Heart Association/American College of Cardiology guideline and the 2014 European Society of Cardiology guideline, which mainly include an unexplained septal hypertrophy with a thickness of >15 mm. Latent LVOTO is defined as an instantaneous peak Doppler left ventricular outflow tract pressure gradient <30 mmHg at rest, while during physiological provocation, such as Valsalva manoeuvre, standing, and exercise, the left ventricular outflow tract pressure gradient is 30 mmHg [1,9]. All patients underwent polysomnography
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53
58 59 60 61 62 63 64 65 66 67 68 69
(PSG) before and 3 months after surgery. Demographic and clinical data of the patients were collected during the hospital stay and 3 months after surgery. The study was approved by the ethics committees of Fuwai Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained from all patients, in accordance with the principles of the Declaration of Helsinki.
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Echocardiography
77
Echocardiographic examinations were performed by one experienced physician. Cardiac chamber diameters were expressed as the maximum value of the anteroposterior diameter in cardiac cycles. The diameter of the ascending aorta was approximately 4 cm above the aortic valve during diastole. The thicknesses of the interventricular septum (IVS) and ventricular wall were determined during diastole. Aside from maximum thickness, the representative thickness of the IVS, which is usually the thickness of the point 25 mm under the right coronary sinus nadir, was also recorded to indicate overall thickness. Left ventricular outflow tract gradient was calculated using the simplified Bernoulli equation. The measurements of left ventricular (LV) ejection fraction were determined by following the American Society of Echocardiography recommendations. More detailed methods are provided in our previous publication [10].
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Cardiac Surgery
94
As described previously [11], we performed an extended Morrow procedure. The hypertrophic ventricular septum resulting in systolic anterior motion of the mitral valve and LVOTO was resected. The resection ranges were as follows: in the long axis, the myectomy started from approximately 4 mm below the aortic ring to the apex of the left ventricle; in the short axis, the myectomy started rightward to the nadir of the right aortic cusp and terminated near the mitral anterior commissure. Hypertrophy of the LV anterior free wall leading to left ventricular outflow tract (LVOT) narrowing may also need resection. Furthermore, the anomalous chordal attachments
Figure 1 Flow diagram of study patients.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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affecting the LVOT were also excised. If intra-operative transoesophageal echocardiography detected a postoperative LVOT gradient >30 mmHg or more than mild-to-moderate mitral valve regurgitation after weaning from cardiopulmonary bypass, re-operation was required. Concomitant surgery was performed based on expert consensus among the experienced cardiac surgeons.
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Polysomnography
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Polysomnography was performed in all participants using standard PSG techniques (Embletta; Embla, Woodbridge,
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UK) before and 3 months after surgery. This investigation consisted of monitoring of the electroencephalogram, electrooculogram, submental electromyogram, electrocardiogram, thoraco-abdominal excursions, oronasal airflow by an airflow pressure transducer, and arterial oxygen saturation by pulse oximetry. Obstructive apnoea was defined as the absence of oronasal airflow for at least 10 s in the presence of out-of-phase thoracoabdominal effort. Hypopnoea was defined as a 50% reduction in oronasal airflow for 10 s associated with a 3% decrease in oxygen saturation. The apnoea–hypopnoea index (AHI) was calculated as the mean
Table 1 Baseline characteristics of the study population. Variable
Total (n = 85)
No OSA (n = 36)
OSA (n = 49)
p
Age (y)
48.6 11.7
42.86 10.8
52.5 10.8
<0.001
BMI (kg/m2)
25.4 3.1
24.9 3.30
25.72 2.96
0.395
Male
54 (63)
24 (67)
30 (61)
0.607
HR (bpm)
70.0 (65.0-75.0)
70.0 (64.2-74.5)
72.0 (64.7-75.0)
0.298
Course of disease (y)
4.0 (1.0-6.0)
3.4 (0.0-5.0)
4.0 (2.0-7.50)
0.059
NYHA class
2.6 0.6
2.6 0.6
2.6 0.5
0.765
Family history of HCM or SCD
19 (22)
13 (36)
6 (12)
0.009
Beta blockers Calcium channel antagonist
79 (93) 8 (9)
34 (94) 3 (8)
45 (92) 5 (10)
0.643 1.000
Chest pain
21 (25)
10 (28)
11 (22)
0.574
Amaurosis
8 (9)
1 (3)
7 (14)
0.156
Syncope
13 (16.5)
2 (6)
11 (24.4)
0.042
Chest distress
57 (67)
23 (64)
34 (69)
0.594
Glucose (mmol/L)
4.5 (4.2-4.8)
4.2 (4.0-4.6)
4.6 (4.3-5.1)
0.005
hs-CRP (mg/L)
1.1 (0.4-1.5)
1.0 (0.6-1.3)
1.1 (0.3-2.3)
0.816
BNP (pg/mL) Endothelin (pmol/L)
1546.0 (840.1-2504.5) 0.4 (0.2-0.5)
1688.0 (1373.0-2608.0) 0.2 (0.1-0.3)
1464.5 (557.8-2701.5) 0.5 (0.4-0.7)
0.223 0.003
SaO2
95.7 (94.3-96.3)
96.0 (95.1-96.4)
95.4 (93.1-96.1)
0.045
LAD (mm)
45.90 6.33
44.93 6.88
46.56 5.91
0.319
IVST (mm)
22.57 4.26
24.64 4.38
21.15 3.57
0.001
LVEF (%)
70.0 (64.0-75.0)
72.0 (62.0-75.0)
70.0 (65.0-75.0)
0.464
LVEDD (mm)
42.0 (38.0-45.0)
39.0 (37.0-42.0)
43.5 (39.0-46.0)
0.001
RAD (mm)
21.0 (20.0-22.8)
21.0 (20.0-23.0)
21.0 (18.0-24.0)
0.330
LVPWT (mm) LVOTG (mmHg)
11.5 (10.0-13.8) 77.3 25.1
11.0 (10.0-13.0) 77.3 29.1
12.0 (10.0-14.0) 85.8 26.3
0.119 0.225
Ascending aorta diameter (mm)
31.0 (29.0-34.0)
30.0 (27.5-32.0)
32.0 (30.0-35.0)
0.044
Moderate or severe MR
46 (66.7)
11 (39.3%)
35 (85.4)
<0.001
AF
11 (13)
1 (3)
10 (20)
0.039
MVO
19 (22)
13 (36)
6 (12)
0.009
RVOTO
2 (2)
0 (0)
2 (4)
0.135
Myocardial bridge
26 (31)
13 (36)
13 (26)
0.344
Latent LVOTO Pulmonary hypertension
17 (20) 8 (9)
12 (33) 0 (0)
5 (10) 8 (16)
0.008 0.018
Data are n (%), mean standard deviation, or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; BMI, body mass index; HR, heart rate; bpm, beats per min; NYHA, New York Heart Association; HCM, Q4
hypertrophic cardiomyopathy; SCD,? ??; hs-CRP, high-sensitivity C-reactive protein; BNP, brain natriuretic peptide; LAD, left atrial diameter; IVST, interventricular septal thickness; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; RAD, right atrial diameter; LVPWT, left ventricular posterior wall thickness; LVOTG, left ventricular outflow tract gradient; MR, mitral regurgitation; AF, atrial fibrillation; MVO, middle ventricular obstruction; RVOTO, right ventricular outflow tract obstruction; LVOTO, left ventricular outflow tract obstruction.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 2 Preoperative polysomnography parameters.
Q5
Variable
No OSA (n = 36)
OSA (n = 49)
p
AHI (1/h) Longest apnoea and hypopnoea time (s)
1.0 (0.2-1.9) 24.4 (19.7-42.6)
12.4 (7.20-22.2) 71.6 (55.2-94.3)
<0.001 <0.001
OAI (1/h)
0.8 (0.3-1.9)
11.3 (6.6-21.4)
<0.001
CAI (1/h)
0.0 (0.0-0.1)
0.3 (0.0-1.5)
0.001
Hypopnoea index (1/h)
0.6 (0.1-1.7)
2.6 (0.4-5.2)
<0.001
Lowest PO2 (%)
88.0 (82.5-90.0)
81.0 (75.0-86.0)
0.002
Snoring time ratio (%)
4.3 (0.6-8.9)
8.7 (3.2-15.1)
0.020
Mean PO2 (%)
94.5 (92.9-95.5)
89.7 (87.6-90.7)
<0.001
ODI (1/h) Mean PO2 decline degree (%)
3.21 3.35 4.48 1.02
15.83 13.87 5.87 1.81
<0.001 <0.001
Total sleep time <90% SpO2
0.1 (0.0-4.5)
8.4 (1.3-16.5)
<0.001
Supine time (min)
252.00 106.40
269.30 108.61
0.896
Total sleep time (min)
533.0 (507.3-575.4)
529.0 (492.0-578.6)
0.922
Data are mean standard deviation or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; AHI, apnoea–hypopnoea index; OAI, obstructive apnoea index; CAI, central apnoea index; ODI, oxygen desaturation index.
126 127
number of apnoeas and hypopnoeas per hour of sleep. If the AHI is >5, it is defined as the OSA group.
128
Statistical Analysis
148
The Kolmogorov–Smirnov test was used to assess normal distribution of continuous variables. The results were expressed as mean standard deviation (SD), median (interquartile range [IQR]), or percentage, when appropriate. The Student’s t-test for independent samples and the Mann–Whitney U-test were used to compare continuous variables as appropriate, and the x2 or Fisher’s exact test were used to compare nominal variables as appropriate. Spearman correlation analysis was performed to estimate the correlations between polysomnography parameters and glucose or left ventricular end-diastolic diameter (LVEDD) or interventricular septum thickness and between the DAHI and other parameters. Multivariate linear regression models were performed for DAHI. Variables with a p-value <0.1 on univariate analysis were entered into a multivariate analysis. All reported probability values were two-tailed, and a p-value <0.05 was considered statistically significant. SPSS version 24.0 statistical software (IBM) and GraphPad Prism 7.0 (GraphPad Software, La Jolla, CA, USA) were used for calculations and illustrations, respectively.
149
Results
150
Baseline Patient Characteristics
151
We enrolled 85 patients who underwent septal myectomy (Figure 1). The baseline characteristics of the entire population, as well as subgroups according to the absence or
129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147
152 153
presence of OSA, are described in Table 1. Obstructive sleep apnoea was present in 49 patients (58%). Patients with OSA were older. Compared with patients without OSA, patients with OSA had an enlarged ascending aorta (median, 32.0 [IQR, 30.0-35.0] vs 30.0 [IQR, 27.5-32.0]; p = 0.044) and LVEDD (median, 43.5 [IQR, 39.0-46.0] vs 39.0 [IQR, 37.042.0]; p = 0.001). Nevertheless, patients without OSA had relatively thicker interventricular septal thickness (IVST) (mean SD, 24.64 4.38 vs 21.15 3.57; p = 0.001). In addition, the prevalence of AF (20.4% vs 2.8%; p = 0.039) and pulmonary hypertension (16.3% vs 0%; p = 0.018) were significantly higher in patients with OSA. The prevalence of middle ventricular obstruction (12.2% vs 36.1%; p = 0.009) and latent LVOTO (10.2% vs 33.3%; p = 0.008) were significantly higher in patients without OSA.
Preoperative Polysomnography Parameters Preoperative sleep study parameters are summarized in Table 2. Compared with patients without OSA, almost all PSG parameters, including AHI, obstructive apnoea index (OAI), central apnoea index (CAI), hypopnoea index (HI), lowest pO2, oxygen desaturation index, mean pO2, and snoring time ratio, were significantly altered. However, no difference was noted in total sleep time between the two groups. In addition, a strong correlation of lowest oxygen saturation (rs=–0.328, p = 0.037), snoring time ratio (rs = 0.499, p = 0.001), and total sleep time <90% SpO2 (rs = 0.347, p = 0.026) with LVEDD was found in patients with OSA, and not AHI, OAI, or HI. A correlation was also noted between oxygen desaturation index and plasma glucose levels (rs = 0.318, p = 0.049) and enlarged
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
154 155 156 Q14
157 158 159 160 161 162 163 164 165 166 167 168
169 170 171 172 173 174 175 176 177 178 179 180 181 182 183
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Table 3 Perioperative clinical data. Variable
No OSA (n = 36)
OSA (n = 49)
p
Duration of CPB (min) Aortic cross-clamp time (min)
89.5 (79.0-120.0) 58.5 (51.3-80.8)
98.0 (79.0-147.5) 59.0 (47.0-97.5)
0.328 0.912
Duration of postoperative ventilation (h)
18.0 (15.0-21.8)
18.5 (16.0-24.0)
0.160
Length of ICU stay (h)
48.0 (28.3-72.0)
48.0 (24.0-85.5)
0.845
Weight of resected myocardium (g)
10.65 4.76
9.01 3.12
0.006
Postoperative AF
4 (11)
15 (31)
0.03
Postoperative LVEF (%)
61.0 (60.0-65.0)
60.0 (60.0-63.8)
0.465
Septal myectomy alone
25 (69)
32 (65)
0.688
CABG Double valve replacement
0 (0) 0 (0)
2 (4) 1 (2)
0.506 1.000
Mitral valve replacement
0 (0)
2 (4)
0.506
Mitral valvuloplasty
8 (22)
9 (18)
0.661
Maze procedure
1 (3)
4 (8)
0.297
Coronary myocardial bridge unroofing
3 (8)
5 (10)
0.770
Length of postoperative hospital (d)
7.0 (7.0-8.0)
7.0 (7.0-9.5)
0.427
WPW pathway amputation
2 (6)
0 (0)
0.176
Pacemaker implantation
0 (0)
4 (8)
0.134
Data are n (%), mean standard deviation, or median (interquartile range). Abbreviations: OSA, obstructive sleep apnoea; CBP, cardiopulmonary bypass; ICU, intensive care unit; AF, atrial fibrillation; LVEF, left ventricular ejection fraction; CABG, coronary artery bypass grafting; WPW, Wolff–Parkinson–White syndrome.
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ascending aorta (rs = 0.401, p = 0.009). In addition, no patient underwent CPAP treatment before operation.
185
Effect of Obstructive Sleep Apnoea on the Perioperative Period
186 187 188 189 190 191
Q15
192
Q6 Q7
The effects of OSA on perioperative period are summarised in Table 3. The incidence of AF was significantly higher (11.1% vs 30.6%; p = 0.033) and the weight of resection myocardium was lower (9.01 3.12 vs 10.65 4.76; p = 0.006) in patients with OSA than those in patients without OSA.
However, no difference was found between the two groups of patients in terms of cardiopulmonary bypass time, aortic cross-clamp time, intensive care unit stay time, and concomitant operation (Table 3).
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Clinical Parameters Before and 3 Months After Septal Myectomy
197
As shown in Table 4, there was no significant change in body mass index before and after surgery in the two groups. Overall, compared to the preoperative data, left ventricular
Q16 199
Table 4 Clinical parameters before and 3 months after septal myectomy. Variables
Patients with OSA Preoperative
Patients without OSA Postoperative
Preoperative
Postoperative
pa
BMI (kg/m2)
25.7 2.96
25.5 2.66
24.9 3.29
24.8 3.13
0.21
LVOTG (mmHg)
85.8 26.3
13.3 7.6b
77.3 29.1
9.4 4.4b
0.009
NYHA class
2.6 0.6
1.2 0.5b
2.6 0.5
1.1 0.4b
0.387
Use of pain or sleeping medications
–
–
0 (0%)
0 (0%)
1.00
Moderate or severe MR (%)
35 (85)
3 (7)b
11 (39)
2 (7)b
0.978
IVST (mm)
21.15 3.57
13.3 2.6
24.64 4.38
14.3 3.8b
0.254
b
Data are n (%) or mean standard deviation. *p < 0.05, preoperative vs postoperative. Abbreviations: OSA, obstructive sleep apnoea; BMI, body mass index; LVOTG, left ventricular outflow tract gradient; NYHA, New York Heart Association; MR, mitral regurgitation; IVST, interventricular septal thickness. a
Patients with and without OSA postoperatively.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 5 Effects of septal myectomy on obstructive sleep apnoea (OSA). Variable
Patients with OSA Preoperative
Q8
Patients without OSA Postoperative
p
Preoperative
Postoperative
p
AHI (1/h)
11.7 (7.2-22.1)
25.6 (17.7-33.8)
<0.001
1.0 (0.2-1.9)
1.9 (0.8-3.3)
0.079
Mix index (1/h)
0.0 (0.0-0.35)
0.1 (0.0-1.4)
0.915
0 (0-0)
0 (0-0)
0.915
OAI (1/h) CAI (1/h)
11.6 (6.8-17.6) 0.4 (0.0-2.1)
15.1 (9.5-20.8) 0.2 (0.0-0.8)
0.024 0.008
0.8 (0.3-1.9) 0.0 (0.0-0.1)
0.5 (0.1-1.1) 0.0 (0.0-0.1)
0.210 0.232
HI (1/h)
4.4 (2.5-7.1)
8.3 (4.1-12.0)
0.003
0.6 (0.1-1.7)
1.3 (0.5-2.3)
0.141
Lowest PO2 (%)
81.0 (74.5-86.0)
80.0 (70.5-84.0)
0.251
88.0 (82.5-90.0)
84.0 (78.0-89.0)
0.318
Snoring time ratio (%)
8.7 (3.2-15.1)
12.6 (3.1-22.5)
0.003
4.3 (0.6-9.0)
6.8 (0.4-10.5)
0.187
Mean PO2 (%)
89.7 (87.2-90.8)
93 (90.1-94.0)
0.001
94.5 (92.9-95.5)
92.1 3.0
0.050
ODI (1/h)
15.8 13.9
20.6 16.3
0.016
3.2 3.4
5.2 5.6
0.124
Mean PO2 decline degree (%)
5.9 1.8
6.3 1.9
0.008
4.5 1.0
4.6 (4.4-5.3)
0.442
Total sleep time <90% SpO2 Supine time (min)
8.4 (1.3-16.5) 269.3 108.6
8.7 (1.5-23.8) 252.2 123.2
0.476 0.247
0.1 (0.0-4.5) 252.0 106.4
3.1 (0.0-37.8) 195.9 101.9
0.150 0.044
Total sleep time (min)
529.0 (492.0-578.6)
525.9 (490.1-573.1)
0.124
533.0 (507.3-575.4)
540.4 (502.2-571.0)
0.891
Data are mean standard deviation or median (interquartile range). Abbreviations: AHI, apnoea hypoxia index; OAI, obstructive apnoea index; CAI, central apnoea index; HI, hypopnoea index; ODI, oxygen desaturation index.
202 203 204 205 206 Q17 207 208 209 210 211 212 213 214 215 216 217 218
outflow tract gradient (LVOTG), New York Heart Association class, IVST, and the percentages of moderate or severe mitral regurgitation were significantly improved. However, compared to patients without OSA, patients with OSA had a relatively higher LVOTG after surgery (13.3 7.6 vs 9.4 4.4; p = 0.009).
Changes in Polysomnography Parameters Before and After Surgery We studied the changes in the parameters pre- and postoperatively. We found no changes in patients without OSA. However, the AHI, OAI, and HI were significantly increased in almost all patients with OSA (median, 11.7 [IQR, 7.2-22.1] vs 25.6 [IQR, 17.7-33.8] [p < 0.001]; median, 11.6 [IQR, 6.817.6] vs 15.1 [9.5-20.8] [p=0.024]; and median, 4.4 [IQR, 2.57.1] vs 8.3 [IQR, 4.1-12.0] [p=0.003], respectively), whereas the CAI decreased (median, 0.4 [IQR, 0.0-2.1] vs 0.2 [0.0-0.8]; p=0.008) (Table 5, Figure 2). This result indicates that the
severity of OSA increased significantly after surgery. To further study the cause of the aggravation of OSA, stepwise multiple linear regression demonstrated that mean oxygen saturation and time% with SpO2 <90% were the only variables associated with DAHI (p = 0.026 and p = 0.007, respectively; adjusted R2 = 0.365) (Table 6). In addition, not all patients were treated with CPAP during hospitalisation and after discharge.
219
Discussion
227
To our knowledge, this study is the first to investigate systematically the relationship between HOCM and OSA in patients undergoing septal myectomy. The main findings are as follows. Firstly, the incidence of OSA in patients with HOCM was up to 58%. Secondly, OSA was associated with higher AF incidence during the perioperative period of septal myectomy. Thirdly, the severity of OSA significantly
228
Figure 2 Changes in apnoea–hypopnea index (AHI) before and after septal myectomy in patients with and without obstructive sleep apnoea.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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Table 6 Multiple linear regression between delta apnoea–hyopnoea index with significant variables from Spearman analysis. Variable
Multivariate adjusted R2 = 0.365
Univariate r
p
B
p
LA
0.419
0.006
0.279
0.064
BMI
0.477
0.444
0.229
0.104
Age
–0.055
0.746
–0.097
0.493
Sex Cardiothoracic ratio
0.423 0.267
0.910 0.092
–0.138 0.117
0.361 0.427
Supine sleep time (min)
–0.356
0.022
0.096
0.526
Oxygen partial pressure
–0.295
0.081
0.047
0.758
Oxygen saturation
–0.279
0.099
–0.013
0.933
PAD (mm)
0.321
0.044
0.016
0.916
Nocturnal mean oxygen saturation
–0.309
0.050
0.159
0.026
Total sleep time <90% SpO2
0.343
0.028
0.159
0.007
Abbreviations: LA, left atrium; BMI, body mass index; PAD = pulmonary artery diameter.
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increased 3 months after septal myectomy, as determined by AHI, OAI, and HI. Finally, the mean oxygen saturation and time% with SpO2 <90% during sleep before surgery were independently associated with the aggravation of OSA after the surgery. Previous studies indicate a high prevalence of OSA in patients with HCM, ranging from 32% to 71% [3]. In the present study, the prevalence of OSA in HCM was consistent with previous studies [5,6,12]. OSA may affect HOCM through multiple mechanisms, including activation of the sympathetic nervous system, increase in heart rate, insulin resistance, and myocardial wall stress, depression of parasympathetic activity, and impairment of vascular endothelial function [13]. Our data showed no difference in heart rate, blood pressure, or plasma catecholamine between patients with and without OSA. However, the levels of plasma glucose and endothelin were significantly higher in patients with OSA. These results indicate that insulin resistance and endothelial dysfunction exist in patients with HOCM complicated by OSA. In the present study, the prevalence of AF in patients with OSA was significantly high. This is consistent with a previous study, which found that the presence and severity of sleepdisordered breathing may influence left atrial volume index and the prevalence of AF in patients with HCM [14]. Intrathoracic pressure shifts, sympathovagal imbalance, and atrial remodelling induced by OSA may play an important role in AF in patients with HCM [15]. Furthermore, the diameter of the aorta and the prevalence of pulmonary hypertension were significantly high in patients with OSA, and a high proportion of latent LVOTO was noted. During OSA, futile inspiratory efforts against the occluded pharynx cause abrupt reductions in intrathoracic negative pressure. On the one hand, this increases left ventricular transmural pressure, and hence the afterload also increases [16]. On the other
hand, venous return is also enhanced, resulting in right ventricular distension and a leftward shift of the IVS [17]. All these mechanisms can aggravate LVOTO and mitral regurgitation. Pulmonary venous hypertension due to LV systolic and diastolic dysfunction is currently speculated to be the most common form of pulmonary hypertension in patients with OSA [18]. However, no difference was found in left atrium diameter between patients with and without OSA. This result may be attributed to the fact that our patients were relatively young. In addition, we found significant correlations between LVEDD and lowest oxygen saturation, snoring time ratio, and total sleep time <90% SpO2, which is the marker for disease severity in HCM [19]. Recurrent activation of the sympathetic system due to oxygen desaturation during sleep apnoea may contribute to the development of HOCM. Prior studies reported that AHI significantly increases after non-cardiac surgery, and that even a few patients without OSA before surgery may develop after it. In these studies, the type of surgery included spinal, orthopaedic, and gynaecological; no patients underwent cardiac surgery. Moreover, general anaesthesia has no effect on postoperative AHI elevation [20,21]. Some studies also found that OSA is independently associated with a higher rate of new cardiovascular events in the long-term follow-up of patients who underwent coronary artery bypass grafting and is an independent predictor of postoperative AF in cardiac surgery [22,23]. In addition, some cardiovascular disease mechanisms exist, including nocturnal rostral fluid shift and less excise, which aggravate the development of OSA [6,24]. The higher prevalence of AF after the surgery in the present study is in accordance with these previous studies. A recent study found that valve repair improves central sleep apnoea, while there was no influence on OSA [25]. However, data on the severity of OSA after septal myectomy are not available to
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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date. Moreover, almost all patients can return to normal life 3 months after surgery, the effects of anaesthesia and sternotomy are eliminated. Therefore, we chose 3 months after surgery as the observation end point, and some patients underwent PSG 6 months after surgery. In our study, in the case of no change in body mass index, we found that AHI, OAI, and HI were significantly increased 3 months after septal myectomy, and a few patients without OSA before surgery may develop after it. This finding is inconsistent with the results obtained in a previous study, which reported that percutaneous transluminal septal myocardial ablation significantly decreases the AHI [26]. Similarly, in patients with severe aortic stenosis and valve regurgitation, a significant improvement in central sleep apnoea (CSA) is noted after transcatheter aortic valve implantation and valve repair [25,27]. There may be several explanations for this. Firstly, in these studies, most of the patients were elderly and had heart failure. Secondly, the method used was cardiopulmonary polygraphy instead of a standard PSG. Thirdly, the decrease in AHI in their research was mainly due to the decline of the CAI, and the type of preoperative sleep apnoea was mainly CSA. A prior study demonstrated that the upper airway changes from a more transversely oriented elliptical shape when supine to a more circular shape when in the lateral recumbent posture, and increased circularity decreases the propensity for tube collapse and may account for the postural dependency of OSA [28]. However, in our patients, no difference was noted in the supine sleeping time before and after the surgery. In multiple linear regression analysis, we found that the mean oxygen saturation and time % with SpO2 <90% during sleep before surgery were independently associated with the aggravation of OSA postoperatively. The night-to-night variability in the frequency of sleep apnoea and hypopnoea and the changes in sleep structure may have contributed to this result [21]. However, the specific mechanism for this is unknown and requires further investigation; it is not clear whether this phenomenon exists in other cardiac surgery patients. In patients with coronary artery disease, timely diagnosis and treatment in those undergoing PCI can serve as a clinically relevant method of secondary prevention to decrease the risk of repeat revascularisation in patients with coronary disease. Importantly, a recent study found that after CPAP treatment in patients with HOCM and OSA, a marked improvement in symptoms and a reduction in LVOTG abrogate the need for septal reduction [2,29]. In the present study, septal myectomy significantly improved the symptoms, cardiac function, and relief of LVOTO. However, when compared with patients without OSA, the postoperative LVOTG was significantly higher in patients with OSA. Therefore, we believe that early diagnosis and timely administration of CPAP treatment should improve the long-term effect of surgery in these patients. The present study has some limitations. Firstly, the sample size was relatively small. We did not include patients with CSA. Therefore, further studies with a larger population are needed to confirm the results. Secondly, we did not monitor
the sleep structure of the patients. Previous studies showed that changes in sleep structure may affect the occurrence and severity of sleep apnoea [21]. Thirdly, a relatively short follow-up period may limit the understanding of long-term postoperative outcomes in patients with HOCM and OSA. In conclusion, OSA is highly prevalent in patients with HOCM and can increase the incidence of perioperative AF of septal myectomy. In addition, the severity of OSA significantly increased 3 months after the operation. The mean oxygen saturation and time% with SpO2 <90% during sleep before operation were independently associated with the increase of AHI. The specific mechanism of such deterioration of OSA after septal myectomy needs to be determined in detail. Long-term follow-up is also necessary to evaluate the dynamic changes of OSA after resolution of the obstruction in patients with HOCM.
362
Conflict of Interest
378
There are no conflicts of interest to disclose.
379
Funding Sources
380
This work was supported by the National Natural Science Foundation of China (grant number: 81570276).
References [1] American College of Cardiology Foundation/American Heart Association Task Force on Practice, American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society. et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg 2011;142: e153–203. [2] Sengupta PP, Sorajja D, Eleid MF, Somers VK, Ommen SR, Parish JM, et al. Hypertrophic obstructive cardiomyopathy and sleep-disordered breathing: an unfavorable combination. Nat Clin Pract Cardiovasc Med 2009;6:14–5. [3] Nerbass FB, Pedrosa RP, Danzi-Soares NJ, Drager LF, Arteaga-Fernandez E, Lorenzi-Filho G. Obstructive sleep apnea and hypertrophic cardiomyopathy: a common and potential harmful combination. Sleep Med Rev 2013;17:201–6. [4] Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217–39. [5] Konecny T, Geske JB, Ludka O, Orban M, Brady PA, Abudiab MM, et al. Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy. Chest 2015;147:1574–81. [6] Pedrosa RP, Drager LF, Genta PR, Amaro AC, Antunes MO, Matsumoto AY, et al. Obstructive sleep apnea is common and independently associated with atrial fibrillation in patients with hypertrophic cardiomyopathy. Chest 2010;137:1078–84. [7] Saurabh Aggarwal MFJ, Agarwa Anushree. Hypertrophic cardiomyopathyassociated with sleep apnea:serious implications andcogent management strategy. Expert Rev Cardiovasc Ther 2015;13:277–84. [8] Nerbass FB, Salemi VMC, Pedrosa RP, Portilho NP, Ferreira-Filho JCA, Moriya HT, et al. Acute effects of nasal CPAP in patients with hypertrophic cardiomyopathy. Chest 2016;150:1050–8. [9] Authors/Task Force members, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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[10]
[11]
[12]
[13] [14]
[15]
[16]
[17]
[18]
[19]
Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733–79. Wang J, Sun X, Xiao M, Zhang M, Chen H, Zhu C, et al. Regional left ventricular reverse remodeling after myectomy in hypertrophic cardiomyopathy. Ann Thorac Surg 2016;102:124–31. Wang S, Cui H, Yu Q, Chen H, Zhu C, Wang J, et al. Excision of anomalous muscle bundles as an important addition to extended septal myectomy for treatment of left ventricular outflow tract obstruction. J Thorac Cardiovasc Surg 2016;152:461–8. Eleid MF, Konecny T, Orban M, Sengupta PP, Somers VK, Parish JM, et al. High prevalence of abnormal nocturnal oximetry in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:1805–9. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82–93. Konecny T, Brady PA, Orban M, Lin G, Pressman GS, Lehar F, et al. Interactions between sleep disordered breathing and atrial fibrillation in patients with hypertrophic cardiomyopathy. Am J Cardiol 2010;105: 1597–1602. Goudis CA, Ketikoglou DG. Obstructive sleep and atrial fibrillation: pathophysiological mechanisms and therapeutic implications. Int J Cardiol 2017;230:293–300. Bradley TD, Hall MJ, Ando S, Floras JS. Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure. Chest 2001;119:1827–35. Brinker JA, Weiss JL, Lappe DL, Rabson JL, Summer WR, Permutt S, et al. Leftward septal displacement during right ventricular loading in man. Circulation 1980;61:626–33. Kholdani C, Fares WH, Mohsenin V. Pulmonary hypertension in obstructive sleep apnea: is it clinically significant? A critical analysis of the association and pathophysiology. Pulm Circ 2015;5:220–7. Maron BJ, Olivotto I, Spirito P, Casey SA, Bellone P, Gohman TE, et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non–referral-based patient population. Circulation 2000;102:858–64.
[20] Chung F, Liao P, Yang Y, Andrawes M, Kang W, Mokhlesi B, et al. Postoperative sleep-disordered breathing in patients without preoperative sleep apnea. Anesth Analg 2015;120:1214–24. [21] Chung F, Liao P, Elsaid H, Shapiro CM, Kang W. Factors associated with postoperative exacerbation of sleep-disordered breathing. Anesthesiology 2014;120:299–311. [22] Wong JK, Maxwell BG, Kushida CA, Sainani KL, Lobato RL, Woo YJ, et al. Obstructive sleep apnea is an independent predictor of postoperative atrial fibrillation in cardiac surgery. J Cardiothorac Vasc Anesth 2015;29:1140–7. [23] Uchoa CHG, Danzi-Soares NJ, Nunes FS, de Souza AAL, Nerbass FB, Pedrosa RP, et al. Impact of OSA on cardiovascular events after coronary artery bypass surgery. Chest 2015;147:1352–60. [24] Yumino D, Redolfi S, Ruttanaumpawan P, Su MC, Smith S, Newton GE, et al. Nocturnal rostral fluid shift: a unifying concept for the pathogenesis of obstructive and central sleep apnea in men with heart failure. Circulation 2010;121:1598–605. [25] Abe H, Takahashi M, Yaegashi H, Eda S, Kitahara H, Tsunemoto H, et al. Valve repair improves central sleep apnea in heart failure patients with valvular heart diseases. Circ J 2009;73:2148–53. [26] Akita K, Maekawa Y, Kohno T, Tsuruta H, Murata M, Fukuda K. Ameliorating the severity of sleep-disordered breathing concomitant with heart failure status after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy. Heart Vessels 2017;32:1320–6. [27] Linhart M, Pabst S, Fistera R, Ghanem A, Sinning JM, Hammerstingl C, et al. Transcatheter valve implantation improves central sleep apnoea in severe aortic stenosis. Eurointervention 2013;9:923–8. [28] Walsh JH, Leigh MS, Paduch A, Maddison KJ, Armstrong JJ, Sampson DD, et al. Effect of body posture on pharyngeal shape and size in adults with and without obstructive sleep apnea. Sleep 2008;31:1543–9. [29] Wu X, Lv S, Yu X, Yao L, Mokhlesi B, Wei Y. Treatment of OSA reduces the risk of repeat revascularization after percutaneous coronary intervention. Chest 2015;147:708–18.
Please cite this article in press as: Wang S, et al. Effect of Septal Myectomy on Obstructive Sleep Apnoea Syndrome in Patients With Hypertrophic Obstructive Cardiomyopathy. Heart, Lung and Circulation (2019), https://doi.org/10.1016/j. hlc.2019.05.190
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