Microvascular cerebral blood flow fluctuations in association with apneas and hypopneas in acute ischemic stroke

Altres ajuts: The authors thank Dr. Arjun Yodh, Dr. John A. Detre, Dr. Janos Lückl, and Rosa Maria Miralda for their useful discussions. They acknowledge the support from Redes Temáticas de Investigación Cooperativa (RETICS-INVICTUS RD012/0014 and RETICS-INVICTUS PLUS RD16/0019/0010), the "Severo Ochoa" Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra Social "la Caixa" Foundation (LlumMedBcn) LASERLAB-EUROPE IV (EU-H2020 654148), "Fundació La Marató TV3" (201709.31), Marie Curie initial training network (OILTEBIA 317526), Societat Catalana de Pneumologia (SOCAP), and Sociedad Española de Neumología y Cirugía Torácica (SEPAR).In a pilot study on acute ischemic stroke (AIS) patients, unexpected periodic fluctuations in microvascular cerebral blood flow (CBF) had been observed. Motivated by the relative lack of information about the impact of the emergence of breathing disorders in association with stroke on cerebral hemodynamics, we hypothesized that these fluctuations are due to apneic and hypopneic events. A total of 28 patients were screened within the first week after stroke with a pulse oximeter. Five (18%) showed fluctuations of arterial blood oxygen saturation (=3%) and were included in the study. Near-infrared diffuse correlation spectroscopy (DCS) was utilized bilaterally to measure the frontal lobe CBF alongside respiratory polygraphy. Biphasic CBF fluctuations were observed with a bilateral increase of 27.1% 17.7% and 29.0% 17.4% for the ipsilesional and contralesional hemispheres, respectively, and a decrease of -19.3% 9.1% and -21.0% 8.9% for the ipsilesional and contralesional hemispheres, respectively. The polygraph revealed that, in general, the fluctuations were associated with apneic and hypopneic events. This study motivates us to investigate whether the impact of altered respiratory patterns on cerebral hemodynamics can be detrimental in AIS patients

Characterization of the microvascular cerebral blood flow response to obstructive apneic events during night sleep

Altres ajuts: This work was funded by the "Severo Ochoa" Programme for Centres of Excellence in R&D (Grant No. SEV-2015-0522), the Obra Social "la Caixa" Foundation (Grant Nos. LlumMedBcn, Programa de Matemàtica Col·laborativa), LASERLABEUROPE IV (Grant No. EU-H2020 654148), Marie Curie initial training network (Grant No. OILTEBIA 317526), Societat Catalana de Pneumologia (SOCAP), and Sociedad Española de Neumología y Cirugía Torácica (SEPAR).Obstructive apnea causes periodic changes in cerebral and systemic hemodynamics, which may contribute to the increased risk of cerebrovascular disease of patients with obstructive sleep apnea (OSA) syndrome. The improved understanding of the consequences of an apneic event on the brain perfusion may improve our knowledge of these consequences and then allow for the development of preventive strategies. Our aim was to characterize the typical microvascular, cortical cerebral blood flow (CBF) changes in an OSA population during an apneic event. Sixteen patients (age , 75% male) with a high risk of severe OSA were measured with a polysomnography device and with diffuse correlation spectroscopy (DCS) during one night of sleep with 1365 obstructive apneic events detected. All patients were later confirmed to suffer from severe OSA syndrome with a mean of apneas and hypopneas per hour. DCS has been shown to be able to characterize the microvascular CBF response to each event with a sufficient contrast-to-noise ratio to reveal its dynamics. It has also revealed that an apnea causes a peak increase of microvascular CBF () at the end of the event followed by a drop () similar to what was observed in macrovascular CBF velocity of the middle cerebral artery. This study paves the way for the utilization of DCS for further studies on these populations

The effect of respiratory event type and duration on heart rate variability in suspected obstructive sleep apnea patients

Abstract. Obstructive sleep apnea (OSA) patients have often reduced long-term heart rate variability (HRV) which is a known risk factor for several cardiovascular diseases such as hypertension and stroke. Albeit OSA being actively studied, it has remained uncharacterized how the duration and type of respiratory events affect the heart rate (HR), i.e. RR intervals, and ultra-short-term HRV during and immediately after the individual respiratory events. This study aimed to investigate whether the changes in ultra-short-term HRV and HR are modulated by the duration and type of the individual respiratory events and whether these changes are sex-specific. It was hypothesized that longer respiratory events cause higher ultra-short-term HRV and greater differences between RR intervals during and after the respiratory event. Moreover, it was hypothesized that the higher HRV and greater differences in HR are associated with apneas and men stronger than hypopneas and women. Electrocardiograms (ECG) of 862 suspected OSA patients were collected during clinical polysomnography (PSG) at the Princess Alexandra Hospital (Brisbane, Australia) and they were analyzed retrospectively. Ultra-short-term HRV was studied with time-domain parameters determined from the ECG segments measured during (in-event) and 15 seconds after (post-event) the respiratory event. The respiratory events of all subjects were divided into groups based on the sex, the type of the respiratory events (apneas and hypopneas), and the duration of the respiratory events (10–20 s, 20–30 s, over 30 s). A clear bradycardia-tachycardia rhythm associated with respiratory events was observed. The ultra-short-term HRV and the difference between in- and post-event RR intervals increased with increasing respiratory event duration. However, the difference between in- and post-event HRV parameter values decreased with increasing duration of the respiratory events. Furthermore, higher ultra-short-term HRV and a greater decrease in RR interval were observed in apneas and men. Based on the results, the duration and type of the respiratory events modulate the HR and ultra-short-term HRV during and after the respiratory events, and these phenomena appear to be sex-specific. Therefore, considering the characteristics of respiratory events and ultra-short-term HRV could be useful in OSA diagnostics when estimating the OSA-related cardiac consequences. A scientific article based on the results of this thesis, Hietakoste et al. Longer apneas and hypopneas are associated with greater ultra-short-term HRV in OSA, has been submitted to a peer-reviewed scientific journal.Tiivistelmä. Uniapneapotilailla havaitaan usein matalaa pitkän aikavälin sykevälivaihtelua, jonka tiedetään myös olevan riskitekijä useille sydän- ja verisuonisairauksille. Ei kuitenkaan tiedetä, miten uniapneaan liittyvät erimittaiset hengityskatkot tai niiden tyyppi vaikuttavat yksittäisten hengityskatkojen aikaiseen ja jälkeiseen ultralyhyeen sykevälivaihteluun ja sydämen lyöntien väliseen kestoon, ts. RR-intervalleihin. Tässä tutkimuksessa tavoitteena oli tutkia ultralyhyen sykevälivaihtelun ja RR-intervallien sukupuolisidonnaisia muutoksia eri mittaisten apneoiden ja hypopneoiden aikana ja jälkeen. Hypoteesina oli, että pidemmät hengityskatkot aiheuttavat suurempia muutoksia hengityskatkojen aikaisen ja jälkeisen keskimääräisen RR-intervallien kestojen välille ja siten korkeampaa ultralyhyttä sykevälivaihtelua. Oletettiin myös, että apneat aiheuttavat suurempia muutoksia kuin hypopneat ja havaitut muutokset ovat suurempia miehillä kuin naisilla. Potilasaineisto koostui 862 uniapneasta epäillyn potilaan sydänsähkökäyristä (EKG), jotka oli mitattu Prinsessa Alexandran sairaalassa (Brisbane, Australia) osana kliinistä unipolygrafiaa. Ultralyhyen sykevälivaihtelun määrittämiseen käytettiin keskimääräistä RR-intervallien kestoa ja aikatason sykevälivaihteluparametreja, jotka määritettiin hengityskatkojen aikaisista ja jälkeisistä (15 s hengityskatkon jälkeen) EKG-segmenteistä. Tutkittavat hengityskatkot jaettiin ryhmiin niiden tyypin (apneat ja hypopneat) ja keston (10–20 s, 20–30 s ja yli 30 s) perusteella. Lisäksi miesten ja naisten hengityskatkoja tutkittiin erikseen. Tutkimuksessa havaittiin, että hengityskatkojen aikaisten ja jälkeisten RR-intervallien ero sekä ultralyhyt sykevälivaihtelu kasvoivat hengityskatkojen keston kasvaessa riippumatta sukupuolesta tai hengityskatkojen tyypistä. Havaittiin myös, että ero hengityskatkojen aikaisten ja jälkeisten sykevälivaihteluparametrien arvojen välillä pieneni hengityskatkojen pidentyessä riippumatta sukupuolesta tai hengityskatkojen tyypistä. Apneat kuitenkin aiheuttivat suuremman muutoksen kuin hypopneat, ja muutokset olivat suurempia miehillä. Tulosten perusteella hengityskatkojen tyyppi ja kesto vaikuttavat ultralyhyeen sykevälivaihteluun ja RR-intervalleihin. Ultralyhyen sykevälivaihtelun ja hengityskatkojen ominaisuuksien huomioonottaminen uniapnean diagnostiikassa voisi olla hyödyllistä arvioitaessa taudin vakavuutta ja sydänterveyteen liittyviä riskejä. Tämän tutkimuksen tuloksista on kirjoitettu tieteellinen artikkeli Hietakoste ym. Longer apneas and hypopneas are associated with greater ultra-short-term HRV in OSA, joka on lähetetty vertaisarvioitavaksi alan kansainväliseen tieteelliseen julkaisusarjaan

Modifikation des morphologischen Scores DES-OSA zur präklinischen Einschätzung einer Obstruktiven Schlafapnoe

Einleitung: Viele OSA-Screening-Scores basieren auf anamnestischen Angaben. Ziel dieser Arbeit war es, den 2016 publizierten DES-OSA Score zur Vorhersage der Schwere einer OSA zu modifizieren. Der DES-OSA Score erfasst ausschließlich anthropometrische und faziale Parameter. Durch eine Modifikation soll der Score vereinfacht und in einem unabhängigen Kollektiv validiert werden. Methode: Die Modifizierung wurde mit 150 deutschen Patienten aus einer multizentrischen Studie (SAGIC, Sleep Apnea Global Interdisciplinary Consortium) vorgenommen und mit einer Gruppe von 50 deutschen SAGIC-Patienten validiert. Die Stärke des Scores wurde separat getestet für die Vorhersage der schweren OSA (AHI ≥ 30/h), der milden bis mittelschweren OSA (5/h ≤ AHI < 30/h) und für den Ausschluss von OSA (AHI < 5/h). Zusätzlich wurde der Score an einem Kollektiv von 150 asiatischen SAGIC-Patienten getestet, um einen ethnischen Vergleich darzustellen und mögliche Grenzen des Scores aufzuzeigen. Ergebnisse: Der modifizierte Score besteht aus fünf Variablen: Body Mass Index, Halsumfang, männliches Geschlecht, einer modifizierten Friedman Scale und Taillenumfang. Nur für Frauen wurde zusätzlich das Alter in den Score integriert. Der Score (≥ 8 Punkte) zeigte bei der Vorhersage der schweren OSA eine Sensitivität von 82%, eine Spezifität von 82% und eine ROC (Receiver Operating Characteristic) AUC (area under the curve) von 0,899. Der Score (5 bis 7 Punkte) zeigte für die Prädiktion der milden bis mittelschweren OSA eine Sensitivität von 68%, eine Spezifität von 73% und eine ROC-AUC von 0,886. Der Score (≤ 4 Punkte) konnte OSA mit einer Sensitivität von 62% und einer Spezifität von 95% und einer ROC-AUC von 0,886 ausschließen. Der modifizierte Score konnte in der Validierungsgruppe mit gleichen Resultaten bestätigt werden. Geschlechteranalysen ergaben eine Schwierigkeit in der Diagnostik der schweren OSA bei Frauen und dem OSA-Ausschluss bei Männern. Der Score versagte bei der Anwendung in der asiatischen Kohorte. Zusammenfassung: Der modifizierte DES-OSA Score (M-DES-OSA Score) konnte erfolgreich angewendet werden, unter anderem durch die Integration einer adaptierten Friedman Scale. Stärken zeigt der Score hinsichtlich der Prädiktion der schweren OSA, was für die damit verbundenen kardiovaskulären Erkrankungen besonders wichtig ist. Auch für den Ausschluss von OSA liefert der Score gute Ergebnisse. Es besteht noch Forschungsbedarf für die Anwendung des Scores nach Geschlecht und in anderen ethnischen Bevölkerungsgruppen.Many obstructive sleep apnea (OSA) prescreening instruments use subjective ratings. The objective of this scientific work was to adapt and validate a fairly new OSA prediction score (DES-OSA) that is based solely on anthropometric measures and facial structures. Methods: The adapted morphologic score was developed with 150 German participants from a multicenter clinical trial called SAGIC (Sleep Apnea Global Interdicsiplinary Consortium) and validated with an independent cohort of 50 German SAGIC participants. Its predictive abilities were tested for severe OSA (AHI ≥ 30/h), mild-to-moderate OSA (5/h ≤ AHI < 30/h), as well as the exclusion of OSA (AHI < 5/h). Gender differences were also analysed, especially due to the huge imbalance in the prevalence of OSA between men and women. Additionally, the score was applied to 150 Asian SAGIC participants for the purpose of ethnical comparison and to reveal possible limits of the score. Results: The adapted score involved five variables: body mass index, neck circumference, male gender, an adapted Friedman Scale, and waist circumference. For women only, age was included. The adapted score (≥ 8 points) predicted severe OSA with a sensitivity of 82%, a specificity of 82%, and a ROC- (Receiver Operating Characteristic) AUC (area under curve) of 0.899. The adapted score (5-7 points) predicted mild-to-moderate OSA with a sensitivity of 68%, a specificity of 73%, and a ROC-AUC of 0.886. The score (≤ 4 points) was able to exclude OSA with a sensitivity of 62%, a specificity of 95%, and a ROC-AUC of 0.886. The adapted score was successfully validated with similar results. Gender analyses revealed that the score was weak to predict severe OSA for women and to predict exclusion of OSA for men. The application with an Asian cohort failed. Conclusion: The morphologic OSA prediction score DES-OSA was adapted successfully. The new score (M-DES-OSA Score) includes, inter alia, a completely new variation of the Friedman Scale. It best predicted severe OSA, especially important due to its high risk of cardiovascular disease, but also predicted the exclusion of OSA. However, the results imply that the score needs to be adjusted for gender specific results and international application