Impaired Pulmonary Diffusing Capacity and Hypoxia in Heart Failure Correlates With Central Sleep Apnea Severity*

doi:10.1378/chest.07-1487

Chest

Volume 134, Issue 1, July 2008, Pages 67-72

https://doi.org/10.1378/chest.07-1487 Get rights and content

Background

Heart failure (HF) is often associated with interstitial pulmonary edema and structural changes, resulting in thickening of the alveolar-capillary membrane and reductions in diffusing capacity of the lung for carbon monoxide (Dlco). Reduced Dlco reflects an impaired efficiency of gas exchange, which may increase plant gain, influence ventilatory control stability, and result in central sleep apnea (CSA). In this study, we test the hypothesis that reductions in Dlco would be associated with increased apnea-hypopnea index (AHI) in patients with CSA.

Methods

Overnight polysomnography, pulmonary function tests, and arterial blood gas analyses were performed in 45 patients with chronic, stable HF. Univariate and multivariate regression analyses were performed in those patients with predominant CSA to test which variables were associated with AHI.

Results

Patients had a mean (± SD) age of 52.7 ± 8.9 years, a mean left ventricular ejection fraction of 26.5 ± 9.9%, and a mean AHI of 22.0 ± 17.4 events per hour. In CSA patients, Dlco and Pao₂ both correlated with total AHI (r = − 0.43, p = 0.046 and r = − 0.53, p = 0.011, respectively) and with supine AHI (r = − 0.56, p = 0.009 and r = − 0.60, p = 0.004, respectively). In a forward stepwise estimation model, Dlco, Pao₂, and body mass index were independent predictors of total AHI, explaining 51% of variability, as was supine AHI, explaining 64% of variability. Dlco and Pao₂ accounted for 37% of the variability in total AHI and 49% of the variability in supine AHI.

Conclusions

In patients with HF and CSA, reductions in Dlco and Pao₂ are independently associated with respiratory disturbance during sleep. The increase in ventilatory instability may be due to plant gain effects.

Section snippets

Subjects

We evaluated 45 consecutive HF patients who had been referred for polysomnography for investigation of sleep-disordered breathing, meeting the following inclusion criteria: age, 18 to 75 years; and documented ischemic or idiopathic dilated cardiomyopathy of at least 6 months in duration, with left ventricular ejection fraction (LVEF) < 50%, New York Heart Association class II-IV, and stable medical condition at the time of assessment (ie, no hospital admissions or changes in medication for at

Results

Subject characteristics are presented in Table 1, with all results presented as the mean ± SD. There were 13 patients in the stable-breathing group, 16 patients in the OSA group, and 16 patients in the CSA group. Patients with OSA had higher BMI and reduced functional residual capacity (FRC) percent predicted than patients in the stable-breathing group. The CSA and OSA groups had higher AHI and lower minimum Spo₂ during sleep than the stable-breathing group. The CSA group also showed reduced

Discussion

This is the first study to find a significant relationship between Dlco and CSA in patients with HF, thus providing clinical evidence that impaired gas exchange is associated with, and may contribute to, ventilatory instability during sleep. We found that impaired gas exchange across the pulmonary capillary membrane, as measured by Dlco, was independently associated with increased respiratory disturbance during sleep in CSA. Furthermore, although patients with CSA had reduced Paco₂, an

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No significant change in ventilation was observed in the lateral position. The observed marked reduction in DLCO in the seated position was in keeping with previous reports [18,27–29], reflecting the damage of the alveolar-capillary barrier induced by raised pulmonary capillary pressure. Changes in body position did not affect DLCO.
It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep.
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The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (−21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (−5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (−46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (−61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = −0.55, p = 0.032).
In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.
Update on Apneas of Heart Failure With Reduced Ejection Fraction: Emphasis on the Physiology of Treatment: Part 2: Central Sleep Apnea
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In addition, overnight rostral fluid shift to the lungs increases pulmonary congestion in patients with HF, lowering carbon dioxide pressures and predisposing HF patients to CSA (Yumino et al., 2010). It has also been reported that reductions in DLCO and PaO2 in HF patients with CSA are independently associated with respiratory disturbance during sleep (Szollosi et al., 2008). Despite the apparent important role of pulmonary factors in the emergence of CSA, the background and mechanisms of this association are poorly understood (Fox et al., 2017).
Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are highly prevalent in heart failure (HF) and are linked to increased mortality. Impaired pulmonary diffusion capacity [DLCO] and [KCO]) have been suggested to play a key role in CSA-CSR pathophysiology. This study investigated the relationship between HF, CSR, DLCO and KCO in well-characterized HF patients.
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A total of 100 patients were included (age 70.7 ± 9.7 years, 95% male, body mass index 28.9 ± 5.3kg/m², left ventricular ejection fraction 33.5 ± 7.7%, New York Heart Association class III 65%. DLCO and oxygenation were significantly correlated with hypoxemic burden (p < 0.05). Mean oxygen saturation, oxygen desaturation, C-reactive protein level and pH were significantly associated with CSA-CSR severity (p < 0.05).
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The prevalence of sleep-disordered breathing (SDB) in patients with heart failure (HF) is high. Positive airway pressure (PAP) is first-choice therapy, but recent data indicates that PAP therapy may increase mortality in HF patients with reduced ejection fraction (HF-REF) and predominant central sleep apnea (CSA). This study investigated long-term effects of PAP therapy on pulmonary function, including respiratory muscle strength. All patients underwent multichannel cardiorespiratory polysomnography (PSG) and comprehensive lung function testing at baseline and follow-up (mean 588 ± 43 days).
350 patients (mean age 68 ± 10.7 years, 88% male) were included, inspiratory vital capacity, 3.3 ± 0.9 vs 3.2 ± 0.8 L; forced expiratory volume in 1 s, 2.5 ± 0.7 vs 2.4 ± 0.7 L; lung diffusion capacity, 6.2 ± 1.9 vs 5.9 ± 1.8 mmol/min/kPa; correction for hemoglobin, 1.1 ± 0.02 vs 1.1 ± 0.3 mmol/min/kPa/L; and mouth occlusion pressure, 0.42 ± 0.11 vs 0.4 ± 0.12 kPa.
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2016, International Journal of Cardiology
Citation Excerpt :
CSA-CSR is relieved by improving the underlying cardiac function (pump, rhythm and valves) through medications, devices (pacemakers, left ventricular assist device), surgery (valve repair & transplantation) or correction of co-existent medical problems such as anaemia or OSA. Studies into the pathogenesis of CSA-CSR have suggested the following mechanisms: an elevated respiratory drive (due to increased SNA or increase pulmonary vagal afferent activity) [6,7], reduced lung function (i.e., reduced volume and impaired diffusing capacity [8,9]) and a delay in the chemical signal (PaCO2) required to stimulate ventilation reaching the brain from the heart (i.e., due to low cardiac output). The periodic breathing pattern relates to the prevailing PaCO2 level oscillating above and below the apnoea threshold [6].
Central sleep apnoea occurs in about a third of patients with reduced systolic heart failure and is a marker of increased mortality. Such patients usually are older males with advanced heart failure (i.e., high pulmonary wedge pressure), often in atrial fibrillation, with evidence of hyperventilation (i.e., low PaCO₂) in the absence of hypoxemia. Characteristically, ventilation waxes and wanes in a sinusoidal pattern, with mild hypoxemia, occurring in the lighter levels of sleep usually when supine. Snoring may also occur in central sleep apnoea, often at the peak of hyperventilation, sometimes contributing to the confusion or overlap with obstructive sleep apnoea. Central sleep apnoea is associated with orthopnoea, paroxysmal nocturnal dyspnoea and an oscillatory respiratory pattern with an incremental cardiopulmonary exercise study. Importantly, heart failure therapies (e.g., afterload reduction, diuresis, pacemakers, transplantation) attenuate central sleep apnoea. Night to night variability in severity of central sleep apnoea may occur with changes in patients' posture during sleep (less severe when sleeping on-side or upright).

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This research was supported by an Australian Postgraduate Award (to Ms. Szollosi).

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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Chest

Original ResearchSleep MedicineImpaired Pulmonary Diffusing Capacity and Hypoxia in Heart Failure Correlates With Central Sleep Apnea Severity*

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Int J Cardiol

Respir Physiol

Chest

Lancet

Chest

Chest

Chest

Chest

Influence of pulmonary capillary wedge pressure on central apnea in heart failure

Circulation

Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure

Am J Respir Crit Care Med

Sleep-induced periodic breathing and apnea: a theoretical study

J Appl Physiol

Instability of ventilatory control in patients with obstructive sleep apnea

Am J Respir Crit Care Med

Ventilatory control and airway anatomy in obstructive sleep apnea

Am J Respir Crit Care Med

Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure

Am J Respir Crit Care Med

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure: its pathophysiological relevance and relationship to exercise performance

Circulation

Gas diffusion and alveolar-capillary unit in chronic heart failure

Eur Heart J

EEG arousals: scoring and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association

Sleep

A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects

Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research; the report of an American Academy of Sleep Medicine task force

Sleep

Original Research
Sleep Medicine
Impaired Pulmonary Diffusing Capacity and Hypoxia in Heart Failure Correlates With Central Sleep Apnea Severity*