Introduction
Sleep-disordered breathing (SDB) is often reported to cause cardiovascular diseases due to mechanisms, such as intermittent nighttime hypoxemia, followed by oxidative stress, endothelial dysfunction, arousal, sympathetic hyperactivity, changes in intrathoracic pressure, and right and left ventricular (LV) afterload [
1‐
4]. Even patients with SDB who have not developed the cardiovascular disease are likely to have latent and subclinical myocardial dysfunction.
The sleep apnea cardiovascular endpoint (SAVE) study reported negative results regarding the effectiveness of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA). However, because of the large number of patients with poor adherence in the target group, the results were carefully interpreted [
5]. Numerous studies reported that myocardial dysfunction in SDB (mainly OSA) is based on LV diastolic dysfunction [
6‐
9]. In recent years, LV global longitudinal strain (GLS) measured by the two-dimensional speckle tracking technique has attracted attention as an index of latent and subclinical heart failure [
10].
In the past, errors in GLS measurement were problematic because of the echocardiographic equipment and analysis software used. However, recently, the European Association of Cardiovascular Imaging (EACVI)/American Society of Echocardiography (ASE) Industry Task Force published the guidelines for measurement methods. Therefore, errors have virtually disappeared [
11‐
14].
Although the normal values of GLS are still controversial, they have been reported in previous meta-analyses (normal values ranged; −15.9% to −22.1%) [
15]. Potter and Marwick classified cardiac dysfunction according to the absolute value of GLS as follows: GLS<8%, very severe; GLS<12%, severe; GLS 12–16%, reduced; GLS 16–18%, borderline; GLS 18–20%, normal; and GLS>20%, supranormal [
16].
Only a few reports are available on latent and subclinical heart failure in patients with SDB who do not have cardiovascular disease. Few reports have evaluated whether or not CPAP treatment improves myocardial dysfunction. In our study, latent myocardial dysfunction in patients with SDB was evaluated using GLS (cut-off level >−18%), and changes before and after CPAP treatment were examined.
The purposes of this retrospective cohort study were (1) to clarify the association of SDB and LV function measured with echocardiography and two-dimensional strain analysis in patients without structural heart diseases and (2) to determine the effects of CPAP therapy on measurable LV functional parameters.
Discussion
This study investigated latent and subclinical myocardial dysfunction in patients with OSA without cardiac disease and the efficacy of CPAP treatment for damage. The results showed that GLS was lower in patients with moderate to severe OSA than in those with mild OSA and was improved by CPAP treatment. In addition, GLS improved significantly in patients who tolerated CPAP therapy.
LV ejection fraction (LVEF) is the most commonly used cardiac function index, and reduced LVEF worsens cardiovascular prognosis. However, previous reports have shown that LVEF >45–50% is not correlated with cardiovascular mortality [
22]. LVEF does not directly reflect the myocardial contractility but is an index calculated from changes in the area of the LV lumen. GLS is a highly reliable and reproducible index for evaluating LV systolic function and is a strong independent indicator of cardiac prognosis [
23,
24]. GLS can detect myocardial injury with higher sensitivity than LVEF, and its use is recommended in European and American cardiovascular-related guidelines as an index with excellent reproducibility [
25,
26]. GLS is more appropriate than LVEF as an index for detecting myocardial damage before the appearance of structural abnormalities in the heart, such as the subject of this study.
Previous studies showed that GLS is reduced in patients with very severe OSA compared with matched controls [
27]. According to Altekin et al., GLS was significantly lower in patients with OSA than in healthy subjects and decreased along with the OSA severity [
28]. In these reports, the number of subjects was small, and the GLS value, which is a criterion for cardiac dysfunction, was not defined.
In this study, 275 patients, the largest number of patients with OSA evaluated for GLS, were included and a GLS value of −18% or higher was considered indicative of cardiac dysfunction. Compared to the results of previous studies, the difference in GLS values among the three groups is small, and it is controversial whether or not the difference is clinically significant. GLS is useful as an index for detecting early-stage myocardial damage, and in recent years, it has also become an important index for follow-up of Cancer Therapeutics-Related Cardiac Dysfunction. According to the European Society of Cardiology (ESC), American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines, 15% or more relative percentage reduction of GLS from baseline may suggest risk of cardiotoxicity [
26,
29]. Based on these reports, the difference in GLS between the three groups confirmed in this study suggests that moderate to severe OSA can cause subclinical myocardial damage. Multivariate analysis showed that moderate to severe OSA was an independent factor in lowering GLS with or without hypertension. This suggested that the underlying cardiac dysfunction is caused by a mechanism unique to the pathological condition of OSA, such as intermittent hypoxemia and changes in intrathoracic pressure during the night.
The efficacy of CPAP treatment for subclinical and latent LV dysfunction has been reported by several studies [
30‐
32]. In these studies, patient adherence to CPAP treatment was not evaluated; therefore, whether Cor not PAP treatment was effective is debatable.
The SAVE study, reported in 2016, was a randomized controlled trial that examined the effectiveness of CPAP therapy in the secondary prevention of cardiovascular events in patients with moderate to severe OSA and cardiovascular and cerebrovascular diseases [
5]. There were no differences in cardiovascular events between the CPAP and control groups, and the effect of CPAP on cardiovascular events was not proven. Although subanalysis was performed by dividing the CPAP use time into 4 h or more and less than 4 h, the rate of cardiovascular events was lower in the group administered for 4 h or more than in the usual care group. In the present study, adherence to CPAP treatment was evaluated using remote monitoring software (NemLink; Teijin Pharma, Tokyo, Japan).
Among patients with good adherence, GLS improved significantly with CPAP treatment. However, the improvement in the proportion of patients with GLS −18% or higher was not associated with the tolerability of CPAP treatment. It may not have been possible to normalize cardiac function within the observation period of this study, as it may take more time for CPAP treatment to improve cardiac function in patients with impaired cardiac function.
Patients with OSA have potentially advanced cardiac dysfunction, which is considered a significant risk factor for future heart disease. In stage A patients with chronic heart failure, evaluating OSA as a risk factor for heart failure and performing therapeutic interventions is essential.
This study has three main limitations. First, it was a retrospective observational study, and many patients were excluded because of insufficient echocardiographic images to analyze GLS (n=390). In addition, more than half of the patients who started CPAP had not undergone follow-up echocardiography or had poor images. Second, patients who took antihypertensive drugs at the first visit were defined as hypertensive patients in this study. Therefore, subclinical hypertensive patients may have been included in the group of patients without hypertension. Third, the CPAP use status during the one month before follow-up echocardiography was used as the criterion for adherence. Adherence had not been evaluated in any period since the start of CPAP therapy.
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