EXPRESS: Hypoxemia during Sleep and Overnight Rostral Fluid Shift in Pulmonary Arterial Hypertension: a pilot study

Introduction. Sleep-related breathing disorders, including sleep apnea and hypoxemia during sleep, are common in pulmonary arterial hypertension (PAH), but the underlying mechanisms remain unknown. Overnight fluid shift from the legs to the upper airway and to the lungs promotes obstructive and central sleep apnea, respectively, in fluid retaining states. The main objective was to evaluate if overnight rostral fluid shift from the legs to the upper part of the body is associated with sleep-related breathing disorders in PAH. Methods. In a prospective study, a group of stable patients with idiopathic, heritable, related to drugs, toxins, or treated congenital heart disease PAH underwent a polysomnography and overnight fluid shift measurement by bioelectrical impedance in the month preceding or following a one-day hospitalization according to regular PAH follow-up schedule with a right heart catheterization. Results. Among 15 patients with PAH (women: 87%; median [25th;75th percentiles] age: 40 [32;61] years; mean pulmonary arterial pressure 56 [46;68] mmHg; pulmonary vascular resistance 8.8 [6.4;10.1] Wood units), 2 patients had sleep apnea and 8 (53%) had hypoxemia during sleep without apnea. The overnight rostral fluid shift was 168 [118;263] mL per leg. Patients with hypoxemia during sleep had a greater fluid shift (221 [141; 361] mL) than those without hypoxemia (118 [44; 178] mL, p = 0.045). Conclusion. This pilot study suggests that hypoxemia during sleep is associated with overnight rostral fluid shift in PAH.

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Pulmonary Arterial Hypertension

Sleep Disorders ◽

10.1093/med/9780190671099.003.0052 ◽

2019 ◽

pp. 884-896

Author(s):

Hugo Paz y Mar ◽

Neal F. Chaisson

Keyword(s):

Pulmonary Hypertension ◽

Sleep Apnea ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Central Sleep Apnea ◽

Chronic Obstructive ◽

Sleep Related Breathing Disorders ◽

Obstructive Pulmonary Disease ◽

Breathing Disorders ◽

Pulmonary Arterial

The high prevalence of pulmonary arterial hypertension (PAH) in patients with obstructive sleep apnea (OSA) and the putative pathophysiologic connections have been extensively documented. Conversely, patients with established PAH are at risk for sleep-related ventilatory instability, including OSA, central sleep apnea, and nocturnal desaturations. This chapter reviews the prevalence and pathophysiologic interactions of these conditions, the interplay with associated disorders, and the effects of continuous positive airway pressure therapy on pulmonary hemodynamics. In patients with OSA, chronic effects of repetitive hypoxia as well as comorbidities, including chronic obstructive pulmonary disease and left-sided heart dysfunction, play a role in promoting pulmonary hypertension. Sleep disordered breathing, representing a spectrum of sleep-related breathing disorders inclusive of OSA, is highly prevalent among patients with established pulmonary hypertension. Obstructive events, central sleep apnea, and nocturnal hypoxia are within the spectrum of sleep-related breathing disorders in pulmonary hypertension. The mechanisms for these associations remain speculative.

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Sleep-related breathing disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2020-26-1-85-93 ◽

2020 ◽

Vol 26 (1) ◽

pp. 85-93

Author(s):

M. A. Dyachenko ◽

M. A. Simakova ◽

L. S. Korostovtseva ◽

M. V. Bochkarev ◽

N. S. Goncharova ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Left Ventricular ◽

Sleep Related Breathing Disorders ◽

Nocturnal Hypoxemia ◽

Breathing Disorders ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

Background. The data evidence that in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) nocturnal hypoxemia is associated with poor prognosis. Although, data regarding sleep-related breathing disorders (SRBD) prevalence and their association with pulmonary hypertension (PH) severity are scarce.Objective. To evaluate the prevalence and the structure of SRBD in patients with PAH and CTEPH and the relationship of SRBD with PH severity. Design and methods. In a prospective, single-center study we examined 31 patients (45 % male (n = 14)) with a verified diagnosis of precapillary PH: 22,6 % with IPAH; 9,7 % with PAH associated with congenital heart disease; 64,5 % with CTEPH; 3,2 % with PAH associated with connective tissue disease. Patients underwent a general clinical examination, questionnaires, respiratory tests, full videopolysomnography, electrocardiogram, and heart ultrasound (ECHO) examination, clinical and biochemical blood tests, including the assessment of ADMA and NT-proBNP levels.Results. No differences in SRBD pattern in patients with PAH and CTEPH were observed as well as with the severity of PH. A positive correlation was found between the apnea-hypopnea index (AHI) and the end-diastolic left ventricular dimension (ρ = 0,54; p = 0,005); the ventricular diameter ratio (RV/LV) negatively correlated with AHI (ρ = –0,41; p = 0,05). Low peripheral blood oxygen saturation negatively correlated with NT-proBNP level (ρ = –0,40; p = 0.035). ADMA level was increased in all patients, nevertheless no association between ADMA and SRBD severity was found (χ2 = 2,97; p = 0,085).Conclusions. SRBD often occurs among patients with PAH and CTEPH, while the presence of SRBD is not associated with the severity of PH. The severity of SRBD is associated with left heart remodeling. The severity of nocturnal hypoxemia in our group is associated with the increased NT-proBNP level, which is consistent with the idea of a negative prognostic value of nocturnal hypoxemia in patients with PAH and CTEPH.

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Prognostic relevance of sleep apnea syndrome in patients with pulmonary arterial hypertension

European Heart Journal ◽

10.1093/ehjci/ehaa946.2243 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Precek ◽

K Vykoupil ◽

F Kovacik ◽

M Hutyra

Keyword(s):

Pulmonary Hypertension ◽

Sleep Apnea ◽

Pulmonary Arterial Hypertension ◽

General Population ◽

Arterial Hypertension ◽

Left Ventricular ◽

Sleep Study ◽

Prognostic Relevance ◽

Obstructive Sleep ◽

Pulmonary Arterial

Abstract Introduction Sleep disordered breathing (SDB) is a group of ventilatory disorders during sleep which includes obstructive sleep apnea (OSA), central sleep apnea (CSA), and sleep related hypoventilation. In patients with SDB, the prevalence of pulmonary hypertension (PH) ranges from 17% to 52%. While SDB is prevalent in the general population with recent estimates of 20% to 30%, in those with cardiovascular disease, particularly left ventricular failure, there is a higher reported prevalence of 47%. Aims The aims of this study were to determine the prevalence and prognostic relevance of sleep apnea in a cohort of patients with newly diagnosed pulmonary arterial hypertension (ESC/WHO Group 1 pulmonary hypertension). Methods We evaluated prospectively 76 patients with the pulmonary arterial hypertension (mean age 54±16 years; 45% male). All patients underwent right heart catheterisation, clinical assessments, sleep study, standard laboratory testing and evaluation of subjective sleepiness by the Epworth Sleepiness Scale. Sleep test was provided with an ApneaLink Plus, consisting of nasal pressure sensor, respiratory effort band, and pulse oximeter worn on the finger. Subjects previously treated for or diagnosed with SDB were excluded from the study. Results Sleep apnea (SA) – defined as apnea-hypopnea index (AHI) ≥5/h – was found in 59 (77.6%) of the pulmonary arterial hypertension (PAH) patients. Mean AHI in the cohort of PAH patients with SA was 26.1±16.6/h. Mean follow-up was 24 months, during which 15 (19.7%) patients died. Characteristics of parameters related to SA in groups of survivors and deceased are in table 1. From the sleep apnea-related parameters, only time with O2Sat <90% – T90 was significantly associated with mortality (AUC 0.856; 95% CI 0.693 – 1.019; p<0.001). Conclusions The presence of sleep apnea in pulmonary arterial hypertension patients is high. The prevalence of sleep apnea is higher in PAH patients than in the general population. The presence of sleep apnea in patients with PAH was not associated with worse prognosis, but noctural hypoxemia (time with O2Sat <90%) was related to poor prognosis. Sleep apnea in patients with PAH should be screened for systematically. Funding Acknowledgement Type of funding source: None

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A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension

European Respiratory Journal ◽

10.1183/13993003.02638-2017 ◽

2018 ◽

Vol 51 (6) ◽

pp. 1702638 ◽

Cited By ~ 78

Author(s):

Anna R. Hemnes ◽

Anandharajan Rathinasabapathy ◽

Eric A. Austin ◽

Evan L. Brittain ◽

Erica J. Carrier ◽

...

Keyword(s):

Pilot Study ◽

Pulmonary Arterial Hypertension ◽

Angiotensin Converting Enzyme ◽

Arterial Hypertension ◽

Pulmonary Arteries ◽

Converting Enzyme ◽

Open Label ◽

Angiotensin Converting Enzyme 2 ◽

Markers Of Inflammation ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a deadly disease with no cure. Alternate conversion of angiotensin II (AngII) to angiotensin-(1–7) (Ang-(1–7)) by angiotensin-converting enzyme 2 (ACE2) resulting in Mas receptor (Mas1) activation improves rodent models of PAH. Effects of recombinant human (rh) ACE2 in human PAH are unknown. Our objective was to determine the effects of rhACE2 in PAH.We defined the molecular effects of Mas1 activation using porcine pulmonary arteries, measured AngII/Ang-(1–7) levels in human PAH and conducted a phase IIa, open-label pilot study of a single infusion of rhACE2 (GSK2586881, 0.2 or 0.4 mg·kg−1 intravenously).Superoxide dismutase 2 (SOD2) and inflammatory gene expression were identified as markers of Mas1 activation. After confirming reduced plasma ACE2 activity in human PAH, five patients were enrolled in the trial. GSK2586881 was well tolerated with significant improvement in cardiac output and pulmonary vascular resistance. GSK2586881 infusion was associated with reduced plasma markers of inflammation within 2–4 h and increased SOD2 plasma protein at 2 weeks.PAH is characterised by reduced ACE2 activity. Augmentation of ACE2 in a pilot study was well tolerated, associated with improved pulmonary haemodynamics and reduced markers of oxidant and inflammatory mediators. Targeting this pathway may be beneficial in human PAH.

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846 Pulmonary Arterial Hypertension as a Sequela of Untreated Obstructive Sleep Apnea in a Patient with Prader-Willi Syndrome

SLEEP ◽

10.1093/sleep/zsab072.843 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A329-A329

Author(s):

Hina Emanuel ◽

Kevin Kaplan

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Systolic Dysfunction ◽

Morbidity And Mortality ◽

Prader Willi Syndrome ◽

Obstructive Sleep ◽

Pulmonary Arterial

Abstract Introduction Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder characterized by hypotonia, behavioral problems, endocrinopathies, sleep and respiratory abnormalities. Morbidity and mortality in the PWS population is attributable to obesity, cardiovascular problems, and sleep apnea. We report a patient with PWS presenting with pulmonary arterial hypertension (PAH) due to untreated obstructive sleep apnea (OSA). Report of case(s) Our patient is a 17-year-old female with a past medical history of PWS, scoliosis, obesity (BMI 52.46), hypogonadotropic hypogonadism, and type II diabetes. Baseline echocardiogram (ECHO) performed at age 9 revealed an estimated right ventricular systolic pressure (eRVSP) of 32mmHg above right atrial pressure (RAP), tricuspid regurgitation (TR) at 2.8 m/sec with no interventricular septal flattening (IVSF) and right ventricle (RV) systolic dysfunction suggestive of mild PAH. Given significant scoliosis the patient did not qualify for growth hormone therapy. She underwent a polysomnogram (PSG) at age 14 showing severe obstructive sleep apnea; apnea-hypopnea index (AHI) of 22.6 (oAHI 22.6). Patient was subsequently lost to follow up until presenting in acute respiratory failure at age 17. She required endotracheal intubation and was extubated to bilevel PAP (BPAP) with inability to wean off BPAP. At that time an ECHO revealed eRVSP of 55 mmHg above RAP, IVSF, TR at 3.7 m/sec, and RV systolic dysfunction suggestive of moderate to severe PAH and developing right sided heart failure. A PAP titration PSG during this admission revealed hypoxemia with oxygen saturation less than 90% (O2 nadir 70%) 12.6% of total sleep time (TST) and hypoventilation (transcutaneous CO2 max of 57 mmHg with an elevation above 50 mmHg for 100% of TST). Using an inspiratory PAP (IPAP) of 24 cmH2O and expiratory PAP (EPAP) of 14 cmH20 with supplemental O2 of 4LPM the respiratory events and hypoxemia resolved but there was persistence of hypoventilation. Tadalafil was initiated for PAH and BPAP therapy for OSA. Follow up visits 4- and 8-weeks post discharge shows improving PAH (TR 3.6 m/sec, eRSVP 52 mmHg, and mild IVSF) due to BPAP and tadalafil therapies. Conclusion This case highlights the importance of treating OSA in patients with PWS to prevent cardiorespiratory complications and reduce morbidity and mortality. Support (if any) None

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