Structural and functional changes in right heart in patients with obstructive sleep apnea syndrome

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INTRODUCTION

Obstructive sleep apnea (OSA) is the most common sleep disorder [1]. At present, approximately 7% of men and 5% of women in the global population are affected by OSA [2]. Although this condition was first described in 1965 [3], substantial evidence has already been accumulated regarding its detrimental effects on human health, particularly on the cardiovascular system [4–6]. Numerous reports in the scientific data have demonstrated an association between OSA and cardiovascular mortality (relative risk 1.94; 95% confidence interval [CI], 1.39–2.70) [7], coronary artery calcification (odds ratio 1.896; 95% CI, 1.423–2.526) [8], and the risk of the first episode of atrial fibrillation (odds ratio 1.76 95% CI, 1.37–2.13) [9].

It is known that in OSA, negative intrathoracic pressure is generated during inspiratory attempts against upper airway obstruction. This mechanism increases venous return to the right heart chambers and augments preload [10]. Consequently, disturbed respiratory physiology in patients with OSA may potentially result in right heart dysfunction. A detailed analysis of right heart changes in patients with OSA is of particular interest.

This review is devoted to current studies assessing the structural and functional changes occurring in the right heart chambers of patients with OSA.

IMPACT OF OBSTRUCTIVE SLEEP APNEA ON THE STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE RIGHT HEART CHAMBERS

The leading mechanism underlying OSA is the decreased elasticity and collapse of the upper airways during sleep. As a consequence, significant reduction of airflow (hypopnea) or complete cessation of breathing (apnea) results in hypoxemia and hypercapnia, as well as secondary disturbances — predominance of the sympathetic nervous system over the parasympathetic, and systemic vasoconstriction [11].

With regard to right heart involvement in patients with OSA, hypoxia plays a central role. It is well established that hypoxemic pulmonary vasoconstriction leads to elevated pulmonary artery pressure [12]. In patients with OSA, this pathophysiological process becomes chronic and contributes to the development of pulmonary hypertension (PH), as well as dilation and dysfunction of the right heart [13]. In addition, hypoxemia and hypercapnia induce an imbalance between proliferation and apoptosis of vascular wall cells in the lungs, and also between vasodilatory agents — primarily nitric oxide and prostaglandins — and vasoconstrictors such as endothelin-1, angiotensin II, and thromboxane A2 [14]. These disturbances promote obliteration and chronic vasospasm of the pulmonary vasculature, leading to increased pulmonary pressure and, consequently, to PH and right heart dysfunction. For example, a study by Harańczyk et al. in a cohort of 50 patients demonstrated that individuals with OSA and systolic dysfunction of the right ventricle (RV) had higher endothelin-1 concentrations compared with those with preserved RV function: 26.0 ± 13.2 vs. 11.5 ± 10.9 pg/mL (p = 0.04) [15].

STRUCTURAL AND FUNCTIONAL CHANGES IN THE RIGHT HEART CHAMBERS IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Small single-center studies have demonstrated alterations in the geometric and functional parameters of the right heart in patients with OSA. For example, in the study by Harańczyk et al., 77 patients with suspected OSA underwent transthoracic echocardiography and polysomnography. In patients with moderate OSA (apnea–hypopnea index [AHI] 15–29 episodes per hour) and severe OSA (AHI ≥ 30 episodes per hour), compared with those without OSA (AHI < 5 episodes per hour) or with mild OSA (AHI 5–14 episodes per hour), the following differences were observed: larger RV outflow tract diameter: 32.6 ± 3.6 vs. 30.9 ± 2.4 mm (p < 0.05); larger right atrial (RA) area: 21.1 ± 4.8 vs. 17.2 ± 3.2 mm² (p = 0.002); larger mean RV diameter (35.5 ± 7.0 vs. 32.2 ± 4.7 mm (p = 0.02)); and lower tricuspid annular plane systolic excursion (TAPSE): 21.9 ± 4.5 vs. 25.8 ± 4.4 mm (p = 0.04). No statistically significant differences were obtained when comparing lateral tricuspid annular peak e' and s' velocities on tissue Doppler imaging and the values of peak tricuspid regurgitation gradient. In this study, patients with more than 10 apnea episodes per hour exhibited the most pronounced right heart dilation and impaired RV systolic function [16].

Similar findings were reported by Ibn Hadj Amor et al. [17]. A total of 139 patients with OSA and 45 control group patients underwent echocardiography. Compared with the control group, patients with OSA had a significantly larger RV diameter: 20 ± 7.7 vs. 32.4 ± 5.5 mm (p < 0.0001). Systolic pulmonary artery pressure (sPAP) was also significantly higher in patients with OSA: 31.2 ± 8.2 vs. 20.9 ± 9.8 mmHg (p < 0.0001). Among functional parameters of the right heart, median TAPSE values in both groups remained within the normal range; however, they were significantly lower in patients with OSA than in controls: 17.7 ± 4.7 vs. 26.0 ± 5.7 mm (p < 0.0001). Further analysis showed that OSA was independently associated with RV dilation at early stages of the disease, but not with RV systolic dysfunction (RR 0.257; 95% CI 0.114–0.582; p = 0.001). Based on these findings, the authors proposed RV dilation as an early and potentially reversible marker of OSA [17].

The negative impact on the right heart was confirmed in a large meta-analysis by Maripov et al., which included 25 studies with 1503 patients with OSA (AHI ≥ 5) and 796 patients from control group. In patients with OSA, the mean RV diameter was significantly greater — 2.49 cm (95% CI 1.62–3.37; p = 0.0001) [18].

Thus, substantial evidence has accumulated regarding the influence of OSA on the structural parameters of the right heart, specifically demonstrating larger geometric dimensions of the RV and RA in patients with OSA compared with healthy controls.

Discussion of right heart structural parameters in patients with OSA cannot be separated from the evaluation of RV — and, to a lesser extent, RA — functional status.

A number of studies investigating right heart systolic function have yielded conflicting results. For example, Vitarelli et al. reported significantly lower TAPSE values (p < 0.05) in 37 patients with moderate (18 ± 4 mm) and severe (16 ± 4 mm) OSA compared with the control group (23 ± 6 mm). Similar changes were found in other indices, including RV fractional area change (p < 0.05) and tissue Doppler–derived peak s' velocity at the tricuspid annulus (p < 0.05). It should be noted that these parameters did not differ significantly between the control group and patients with mild OSA [19]. Conversely, some studies found no significant differences in conventional parameters of right heart systolic function (TAPSE, RV fractional area change, tricuspid annular s' velocity) between patients with OSA and healthy subjects [20, 21].

Measures of global longitudinal strain (GLS) and RV free wall longitudinal strain are of particular interest in assessing right heart systolic function (especially in the context of subclinical RV dysfunction). In a study by Macek et al., RV free wall longitudinal strain in 33 patients with diagnosed OSA was significantly reduced compared with patients without OSA (n = 10): (27.17 ± 5.60)% vs (−32.64 ± 5.40)% (p = 0.023). No significant correlation was found between OSA severity and RV free wall longitudinal strain [22]. In contrast, a study by Hammerstingl et al. in 154 patients with mild, moderate, and severe OSA demonstrated a progressive reduction in RV GLS with increasing OSA severity: (−20.9 ± 5.8)% in mild OSA group, (−15.5 ± 6.1)% in moderate OSA group, and (−12.7 ± 9.2)% in severe OSA group (p < 0.0001) [21].

Assessment of RA function is also an important component of right heart evaluation. The study by Li et al. included 71 patients with OSA and 30 controls. It was found that RA GLS was significantly lower in patients with moderate OSA compared with controls (33.6 ± 8.2)% and was also significantly lower in patients with severe OSA (30.5 ± 7.8)% (p < 0.05). RA GLS was identified as an independent predictor of OSA severity [23].

In summary, evaluation of right heart systolic function remains a subject of considerable interest. Study findings are inconsistent; however, it is evident that patients with severe OSA are characterized by worse systolic function of both the RV and RA, and not all parameters have prognostic value as predictors of OSA severity.

COMBINATION OF OBSTRUCTIVE SLEEP APNEA AND PULMONARY HYPERTENSION

At present, OSA is included in the World Health Organization classification as one of the nosologies underlying group III PH, or PH associated with lung disease and/or hypoxia [24]. Meanwhile, patients with OSA may have mixed etiologies of PH: post-thromboembolic PH, idiopathic PH, or PH associated with left heart disease [25, 26]. According to Battaglia et al., the impact of OSA on pulmonary artery pressure is minimal in patients without concomitant cardiovascular and respiratory disorders [27]. Clinical diagnosis of PH in patients with OSA presents difficulties. Dyspnea, reduced exercise tolerance, and peripheral edema as PH symptoms are often masked in such patients or interpreted within the context of another cardiovascular condition. The importance of recognizing the combination of OSA and PH was demonstrated in a study by Minai et al. involving 83 patients, in which PH was excluded in 30% using the diagnostic gold standard — right heart catheterization. Survival was compared between patients with and without concomitant OSA and PH at 1, 4, and 8 years of follow-up. Survival rates in patients with OSA and PH were lower, amounting to 93%, 75%, and 43%, compared with 100%, 90%, and 76% in patients with OSA without PH, respectively [28]. It was demonstrated that patients with OSA and diagnosed PH had worse survival, particularly at longer follow-up.

Given these considerations, the question of whether PH in patients with OSA is primary or secondary requires further investigation.

In several studies, no conclusive evidence was obtained demonstrating a direct relationship between the presence of PH and OSA severity. For instance, Yan et al. analyzed clinical and laboratory parameters in 140 patients with PH diagnosed by right heart catheterization. Among them, 35 patients had OSA. Thus, patients with OSA and PH paradoxically demonstrated lower mean pulmonary artery pressure (mPAP) compared with patients with PH without OSA: 53.57 ± 13.08 vs. 56.45 ± 18.19 mmHg (p = 0.01). Interestingly, this study did not find statistically significant differences between the groups in laboratory or clinical parameters: N-terminal pro–B-type natriuretic peptide levels (1263.1 ± 1298.8 vs. 1662.47 ± 1493.71 pg/mL, p = 0.553) and six-minute walk distance (418.66 ± 96.40 vs. 368.56 ± 120.62 m, p = 0.337) [29].

In a meta-analysis by Akbari et al. including 39 studies, characteristics of patients with combined OSA and PH were examined. This meta-analysis demonstrated that mPAP did not differ significantly between patients with OSA and PH and those without PH: −2.4 [−5.1; 0.3] (p = 0.078) [30].

On the other hand, indirect evidence for the presence of PH in patients with OSA is provided by data showing a reduction in pulmonary artery pressure with continuous positive airway pressure (CPAP) therapy. Sajkov et al. noted a decrease in mPAP from 17.0 ± 1.2 to 14.5 ± 0.8 mmHg in 22 patients with OSA after 4 months of CPAP therapy (p < 0.05) [31]. A similar positive effect on pulmonary artery pressure was reported in a study by Arias et al., which compared sPAP in 23 patients with severe OSA (mean AHI 44.1 ± 29.3 episodes/hour) receiving CPAP therapy with that in 10 healthy controls. At baseline, patients with OSA had significantly higher sPAP than controls: 29.8 ± 8.8 vs. 23.4 ± 4.1 mmHg (p = 0.036). After 12 weeks of CPAP therapy, sPAP in patients with OSA decreased to 24.0 ± 5.8 mmHg (p < 0.0001) [32].

The effects of CPAP therapy were further summarized in a meta-analysis by Imran et al. Based on 7 studies including 222 patients with severe OSA (mean AHI 58 episodes/hour), CPAP therapy reduced mPAP by an average of 13.3 mmHg (95% CI 12.7–14.0), with therapy duration ranging from 3 to 70 months [33]. Thus, it can be concluded that active correction of hypoxemia in patients with OSA reduces vasotropic and endothelium-dependent constrictor effects, thereby improving pulmonary hemodynamics.

Taken together, the presence of PH in patients with OSA, its pathogenesis, and its relationship to OSA severity and pulmonary hemodynamic profile remain subjects of ongoing debate.

CONCLUSION

The investigation of the right heart condition in patients with OSA remains a relevant task given the presence of documented structural alterations. Nevertheless, the assessment and interpretation of pulmonary hemodynamic changes — particularly the contribution of PH to disease severity and prognosis in OSA — pose certain challenges. Current evidence is insufficient to conclude that systolic function of the right heart declines proportionally with OSA severity. This underscores the importance of subclinical assessment methods for RV and atrial function.

Further studies on this topic are required, involving larger patient cohorts and more detailed consideration of cardiovascular comorbidities in patients with OSA.

ADDITIONAL INFORMATION

Author contributions: A.A. Karasev: conceptualization, writing — original draft, writing — review & editing; N.G. Poteshkina: supervision, writing — review & editing. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: Not applicable.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities or interests for the last three years related with for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: In creating this work, previously published information (text, illustrations, data) was not used.

Data availability statement: Not applicable (the article is a descriptive literature review).

Generative AI: Generative AI technologies were not used for this article creation.

Provenance and peer-review: The present paper was submitted to the journal in a proactive manner and was subsequently reviewed by editorial board member, editorial council member, and the scientific editor of the periodical in accordance with the standard procedure.

About the authors

Anton A. Karasev

The Russian National Research Medical University named after N.I. Pirogov; Moscow City Clinical Hospital 52

Author for correspondence.
Email: akara95_2010@mail.ru
ORCID iD: 0000-0002-3863-6755
SPIN-code: 2656-1420

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; 3 Pehotnaya st, Moscow, 123182

Nataliya G. Poteshkina

The Russian National Research Medical University named after N.I. Pirogov; Moscow City Clinical Hospital 52

Email: nat-pa@yandex.ru
ORCID iD: 0000-0001-9803-2139
SPIN-code: 2863-4840

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow; 3 Pehotnaya st, Moscow, 123182

References

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