Sleep-disordered breathing and lung function abnormalities in adults with congenital heart disease

Due to advances in diagnosis and treatment, survival to adulthood of patients with congenital heart diseases (CHD) has improved over the last decades. Nonetheless, little is known about pulmonary comorbidities that may be a modifiable disorder in this vulnerable population. Their presence is often underdiagnosed, as their common cardinal symptoms of dyspnoea and fatigue are frequently falsely attributed to the known cardiac condition. Within the spectrum of pulmonary comorbidities, sleep-disordered breathing (SDB) exerts an independent negative effect on cardiovascular function in the general population [1]. Obstructive sleep apnoea (OSA) is characterized by upper airway collapsibility that leads to repetitive apnoeas [2, 3]. The resulting cycles of hypoxaemia might be particularly detrimental in adult CHD (ACHD). Fluid retention and leg oedema have been reported to be accompanied by a nocturnal fluid shift from the legs to the neck and peripharyngeal soft tissues, increasing the propensity to pharyngeal narrowing in heart failure patients [4]. This mechanistic approach supports the notion that adult patients with CHD may be especially susceptible to SDB. Once diagnosed, OSA treatment in ACHD is challenging as positive pressure ventilation impedes systemic venous return by the elevation in intrathoracic pressure and may consequently have deleterious haemodynamic consequences if applied indiscriminately.

Apart from SDB, CHD influences the respiratory system through multiple physiological and anatomical mechanisms. Lung function abnormalities may arise from pulmonary congestion that decreases lung compliance [5]. Fluid retention can even affect the bronchial walls with resultant wheezing. Of note, the co-occurrence of obstructive airflow limitation and OSA, known as “overlap syndrome”, constitutes a distinct disease entity that is characterized by profound nocturnal hypoxaemia and deranged gas exchange during daytime [6, 7]. These effects might be deleterious to the ACHD cohort.

In keeping with this, the aim of the present study was to investigate prospectively the occurrence of SDB in ACHD as a function of the underlying specific CHD lesion and to correlate the results with those obtained by pulmonary function assessment.

The present study prospectively analysed the prevalence of sleep apnoea and lung function abnormalities in an ACHD study population. The main findings are as follows: (i) Sleep apnoea was diagnosed in 39% of patients with ACHD and was predominantly central in nature. (ii) Neither prevalence nor severity of sleep apnoea substantially differed over ACHD lesion groups. (iii) ACHD was accompanied by a remarkable proportion of ventilatory defects of both obstructive and restrictive nature, of which restrictive defects related to the underlying congenital lesion.

Due to remarkable gains in survival, the field of ACHD is witnessing rapid growth. It has led to a shift in the demographics of CHD, where adults now outnumber children by a ratio of 2:1 [15]. In this growing cohort of patients, comorbid conditions—both related to the underlying defect and acquired—are gaining attention, such that improvements in understanding can affect lifelong care. Evidence has emerged to support a substantial prevalence of sleep apnoea in ACHD. However, the currently assessed proportion of patients with concomitant sleep apnoea only slightly exceeded its estimated prevalence in the general, middle-aged population of 5–25% [16]. Prior studies have principally focused on single defects. In a cohort of 22 adult patients who had previously underwent Fontan palliation of single ventricle physiology, polysomnography was retrospectively analysed and revealed an SDB frequency of 77% [17]. This prevalence notably exceeds the one ascertained in our study. This discrepancy might primarily be driven by screening bias, as the aforementioned trial retrospectively examined more symptomatic patients who had undergone polysomnography in routine clinical care and thus had a higher pre-test probability of SDB. Miles and colleagues performed in-home overnight oximetry in patients with CHD and pulmonary valve dysfunction and detected decreased nocturnal oxygen saturation levels in 13 of 22 patients (59%) [18]. Within our group of right-sided lesions, SDB prevalence indeed rose to 48% but was still well below the one reported by Miles et al. This inconsistency might be ascribed to less diagnostic accuracy arising from only oximetry. In a cohort of 20 patients with Eisenmenger syndrome, OSA was polysomnographically diagnosed in 15% of patients, which is equal to the OSA prevalence found in our ACDH study population [19]. Consistent with our findings, OSA did not correlate with the underlying type of shunt but with BMI and age. Drake et al. examined a broader spectrum of CHD lesions by the use of the Berlin Questionnaire that stratifies patients into risk classes of having OSA [20]. They identified a proportion of 31% of patients with ACHD at high risk of OSA that diverges from our results, mainly due to the employed screening tool. A likewise wider range of defects was evaluated by Harada and colleagues [21]. Patients with ACHD who required hospitalization and underwent in-hospital overnight polygraphy were retrospectively analysed. A total of 63% of patients were diagnosed with sleep apnoea with the broad majority obstructive in nature. These data are opposed to our findings and surpass our SDB frequency by far. Diverging results might be traced back to a different study population. Harada et al. examined patients hospitalized for ACHD, presumably implying cardiac decompensation, whilst our study participants were outpatient and excluded from study entry in case of hospitalization due to CHD within the preceding 6 months. In acquired left heart failure, central sleep apnoea is primarily driven by fluid excess in the pulmonary interstitium with elevated pulmonary wedge pressure that stimulates juxtapulmonary receptors and affects chemoresponsiveness of the respiratory centre [22]. However, the mechanisms underlying central abnormalities of SDB in ACHD are less well defined. In infants with cardiomyopathy, central sleep apnoea was observed in 24% of patients [23]. Of note, severity of central sleep apnoea (central apnoea–hypopnoea index) correlated with the left ventricular end diastolic volume index. It supports the concept that left heart failure—whether congenital or acquired—is accompanied by pulmonary congestion that contributes to the severity of sleep apnoea [4].

In terms of lung function abnormalities in ACHD, prior studies have primarily focused on restrictive pulmonary defects. The underlying mechanisms leading to restrictive lung function in ACHD are diverse. They comprehend a less favourable foetal environment and lower physical activity in childhood that compromise lung development. Pulmonary congestion and respiratory muscle weakness, in particular diaphragm dysfunction, may additionally cause restrictive ventilatory defects, the latter being reported to be accompanied by increased inflammation levels [24]. Alonso-Gonzalez and colleagues analysed spirometry data in 1188 ACHD patients and reported a prevalence of 47% of markedly abnormal FVC [25]. The presence and severity of the restrictive defect were related to the complexity of the underlying cardiac lesion. This observation is consistent with our findings insomuch as TLC significantly varied over ACHD groups (Table 4). However, our pulmonary function testing was not limited to spirometry but additionally included body plethysmography to inform on lung volumes and diffusion capacity testing to provide a window on mechanistic inference. DL_CO positively correlated with TLC, supporting the notion of an underlying causative pulmonary congestion. Both TLC and DL_CO were related to exercise capacity.

With regard to obstructive pulmonary defects, Singh et al. studied non-cardiac comorbidities in hospitalized patients with ACHD in a US database and detected COPD in 20% of patients [26]. This proportion slightly outnumbers the frequency of COPD assessed in our study (15%). Noteworthy, we identified obstructive lung disorders in 19% of patients but complemented bronchodilator testing to differentiate between COPD and asthma. Neither obstructive lung defects in general nor COPD differed in frequency over the four ACHD groups. In the present study, we ascertained a prevalence of 3% of overlapping OSA with COPD. This result is consistent with the observations made in the Sleep Heart Health Study by Sanders et al.: the prevalence of OSA was not greater in patients with versus without COPD and ranges from 5 to 25% [27]. In light of our findings, patients with ACHD do not appear to be prone to the development of overlapping OSA and COPD. Like in the general unselected population, the concomitance of both disorders was associated with profound nocturnal desaturation [7].

A study limitation arises from the participation of  a single hospital, a fact that impeded the enrollment of a larger number of patients with ACHD. Study protocol did not allot a control population that would have permitted direct comparison of occurrence of SDB and lung function disorders in healthy controls. Furthermore, we used ambulatory polygraphy for SDB screening, whilst the “gold standard” is overnight attended polysomnography. Though level 3 portable devices have been attributed a high degree of diagnostic accuracy [28], polysomnography would have been a valuable adjunct to validate polygraphy results.

To summarize, patients with ACHD exhibited only a slightly higher vulnerability to sleep apnoea than that reported for the general population. The findings suggest a mild propensity amongst patients with ACHD to develop SDB that is related to established risk factors such as gender, age, and obesity but seems to be unaffected by the underlying congenital lesion. ACHD was accompanied by ventilatory defects of both obstructive and restrictive nature.