Obstructive sleep apnea syndrome (OSAS) has been associated to impaired baroreflex sensitivity (BRS) which has recently been shown to be non-invasively assessed by heart rate turbulence (HRT) analysis. Although HRT seems to be better suited than traditional heart rate variability indexes for autonomic assessment in presence of respiratory and arrhythmic disorders, very few papers addressed its evaluation in OSAS. Aim of the study is to find out whether and to which extend HRT is associated to OSAS severity. We studied HRT in polysomnographic recordings of 221 mild to severe OSAS pts. Results showed that, while HRT onset values did not significantly differ between mild (-0,78±1,50), moderate (-0,89±1,78) and severe (-0,70±1,28) pts., HRT slope significantly decreases (Kruskal-Wallis P value <0.05) from mild (3,27±2,7) to moderate (2,6±2,6) and severe (1,98±2,5) pts., with a significant Dunn's multiple comparisons post test only between mild vs. severe OSAS pts. Data indicate that the main BRS alterations do not appear in the early HRT phase triggered by transient vagal inhibition, but during the slow one, due to the sympathetic hyperactivity affecting the heart rate recovery. These findings support the conclusion that HRT assessment could have a prognostic value related to the development of cardiovascular disease in OSAS

Balzano G

Cesarelli M

D'Addio G

De Felice A

Romano M

English

Archivio della ricerca - Università degli studi di Napoli Federico II

OSAS Severity is Associated with Decreased Heart Rate Turbulence Slope Giovanni D’Addio1, Mario Cesarelli2, Maria Romano2, Alberto De Felice1 1 S Maugeri Foundation, Telese Terme, Italy  2 Bioengineering Dpt. of University Federico II, Naples, Italy Abstract Obstructive sleep apnea syndrome (OSAS) has been associated to impaired baroreflex sensitivity (BRS) which has recently been shown to be non-invasively assessed by heart rate turbulence (HRT) analysis. Although HRT seems to be better suited than traditional heart rate variability indexes for autonomic assessment in presence of respiratory and arrhythmic disorders, very few papers addressed its evaluation in OSAS. Aim of the study is to find out whether and to which extend HRT is associated to OSAS severity. We studied HRT in polysomnographic recordings of 221 mild to severe OSAS pts. Results showed that, while HRT onset values did not significantly differ between mild (-0,78±1,50), moderate (-0,89±1,78) and severe (-0,70±1,28) pts., HRT slope significantly decreases (Kruskal-Wallis P value <0.05) from mild (3,27±2,7) to moderate (2,6±2,6) and severe (1,98±2,5) pts., with a significant Dunn's multiple comparisons post test only between mild vs. severe OSAS pts. Data indicate that the main BRS alterations do not appear in the early HRT phase triggered by transient vagal inhibition, but during the slow one, due to the sympathetic hyperactivity affecting the heart rate recovery. These findings support the conclusion that HRT assessment could have a prognostic value related to the development of cardiovascular disease in OSAS. 1. IntroductionObstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep, leading to significant hypoxia. It is a highly prevalent disease in the population, affecting 1–4% of adults, mostly aging within 30 to 60 years old and just in 19% over 60 [1]. This pathology is usually diagnosed by polysomnographic studies, mainly consisting of nasal and oral breath flow measurements, snoring microphone recordings, thoracic and abdominal movements measurement by stress sensitive belts, and pulse oximetry, scoring OSAS severity by the number of apneas and hypopneas per hour during sleep, defined as apneas/hypopneas index (AHI). This index discriminates from mild (5≤AHI<15) to moderate (15≤AHI<30) and severe (AHI≥30) OSAS grade and has been associated to worse prognosis and mortality, mainly due to an increased rate of cardiovascular morbidity. Changes of the cardiac autonomic regulation are considered to be involved in the development of cardiovascular disease in patients with OSAS [2]. Sympatho-vagal balance is usually assessed by measuring heart rate variability [3-9] but some studies have questioned the validity of spectral heart rate variability measurements in the presence of sleep disordered breathing [10] mainly both for nonstationarity due to nonlinear heart period modulation caused by highly dynamic pathological respiratory patterns and for the elevated incidence of cardiac arrhythmias, including ventricular premature complexes (VPC) and sequences of tachycardia-brachycardia. OSAS has been associated to impaired baroreflex sensitivity during sleep, which may contribute to the cardiovascular pathophysiology in these patients [11]. HRT has been recently shown as an attractive non-invasive way of baroreflex sensitivity assessment [12] and its impairments has been demostrated as the strongest electrocardiographic risk predictor in cardiac patients [13]. HRT consists on the analysis of short-term sinus cycle length fluctuations following spontaneous isolated VPC. The physiologic pattern of HRT is composed by a brief heart rate acceleration followed by a more gradual heart rate deceleration before the rate returns to a pre-ectopic level. Available physiologic investigations confirm that the initial heart rate acceleration is triggered by transient vagal inhibition in response to missed baroreflex afferent input caused by hemodynamically inefficient ventricular contraction. A sympathetically mediated overshoot of arterial pressure is responsible for the subsequent heart rate deceleration through vagal recruitment. Although HRT seems to be better suited than traditional heart rate variability indexes for autonomic assessment in presence of respiratory and arrhythmic disorders, very few papers addressed its evaluation in OSAS. Aim of the study is to find out whether and to which extend HRT is associated to OSAS severity. ISSN 2325-8861 Computing in Cardiology 2013; 40:1007-1010.10072. Methods 2.1. Study population Only patients with newly diagnosed OSA defined by an apnea-hypopnea index (AHI) of at least 5 events per hour during polysomnography were taken into analysis. We studied HRT in polysomnographic recordings of 90 mild (5<AHI<15), 79 moderate (16<AHI<30) and 72 severe (AHI>30) OSAS pts. (age 62±14, 71% males). admitted in the Pneumological Rehabilitation Unit Institute of Maugeri Foundation of Telese Terme (BN, Italy). Exclusion criteria were defined as follows: treatment with betablocking agents or theophylline, history of cardiac disease, left ventricular dysfunction (ejection fraction < 50%), diabetes mellitus, and periodic breathing pattern.  2.2. Polysomnographic monitoring Additionally to traditional polysomnographics signals of breath flow, snoring, thoracic and abdominal movements and pulse oximetry, all subject underwent to an holter ecg monitoring between 11 p.m. and 6 a.m, contemporary available by means of Somntè (Compumedics) polysomnograhic system. Apneas has been defined as an airflow amplitude reduction of at least the 80% for more than 10 s and hypopneas were defined as an airflow amplitude reduction of at least the 50% for more than 10 s with a fall of at least the 4% in oxygen saturation and AHI of all recordings has been automatically calculated by the system with an algorithm for respiratory pattern recognition and manually verified by an expert technician. Each heart beat has been labeled as normal, VPC or aberrant according to recognition by the system with an algorithm for ecg holter analysis and after an investigator’s verification.  2.3. HRT Analysis All data has been imported from Somntè database and post-processed for HRT analysis by a customized Matlab software toolbox developed by the authors [14-16]. Accordingly to standards of measurements [13], HRT was estimated by two numerical descriptors: turbulence onset (TO), reflecting the initial phase of sinus rhythm acceleration and turbulence slope (TS), describing the late deceleration phase. TO was calculated as a percentage difference between the mean of the first two RR intervals following the compensatory pause after a VPC and the last two sinus RR intervals before a VPC. TS was calculated as the maximum positive slope of a regression line assessed over any of 5 consecutive RR intervals within the first 15 sinus RR intervals after a VPC. Filtering algorithms were used to eliminate inappropriate RR intervals and VPC with overly long coupling intervals or overly short compensatory pauses. Filtering algorithms excluded from the HRT calculation RR intervals with the following characteristics: <300 ms, >2000 ms, >200 ms difference to the preceding sinus interval, and >20% difference to the reference interval (mean of the 5 last sinus intervals). In addition, HRT calculation has been limited to VPC with a minimum prematurity of 20% and a post-extrasystole interval that is at least 20% longer than the reference interval (mean of last 5 sinus RR intervals). According to standard guidelines, for reliable construction of the VPC tachogram, all HRT values were then calculated from the averaged tachogram, selecting for the analysis only recordings with at least six isolated VPC, each followed by at least 15 sinus RR intervals (Fig. 1). Since it has recently been reported that TS is structurally related to the number of VPCs and its estimation method induces a mathematically determined increase inversely related to the square root of the VPCs number, a corrected TS (TSc) has been used as followed described[17].  where 	0.02475 13 . √#  and RMMSD is the square root of the mean squared difference of successive normal beat-to-beat differences.   2.4. Statistical analysis Statistical analyses were performed by GraphPad Prism 5.0 software package (GraphPad Software, San Diego California USA). Due to the skewed distributions of all variables (D'Agostino & Pearson omnibus normality test p <0.05), analysis of variance in the three studied groups has been performed by Kruskal-Wallis test followed by Dunn's Multiple Comparison Test between each couple of groups (p=0.05). Descriptive statistics (Table 1) and data plot (Fig. 2 and 3) have therefore been expressed in medians and percentiles. -2 -1 VPC CP 1 2 3 4 5 6 7 8 9 10 11 12 13 14 155006007008009001000RRFigure 1. Examples of HRT curves in mild (black circles) and severe (white circles) OSAS patients. 10083. Results HRT analysis in OSAS patients’ groups (see Table 1) was feasible according to all previous exposed criteria in 82 of 90 mild; 74 of 79 moderate and 65 of 72 severe OSAS patients. In the remaining patients, HRT analyses could not be performed, due to missing single VPCs during sleep. ANOVA of TO and TS in OSAS patients’ groups (see Table 2) showed that, while TO values did not significantly differ between groups, TS significantly decreases from mild to severe patients, with a significant Dunn's multiple comparisons post-test only between mild vs. severe OSAS pts.  Table 1. HRT analysis in OSAS pts’ groups.  Mild Moderate Severe # Analysed Rec. 82 74 65 #VPC 85±113 56±67 90±96 TO (%) 25% perc. -1.4 -1.6 -1.5 TO (%) Median -0.5 -0.5 -0.8 TO (%) 75% perc. 0 0.1 0.1 TS (ms/RR) 25% perc. 1.2 0.6 0.2 TS (ms/RR) Median 2.6 2.0 1.6 TS (ms/RR) 75% perc. 4.5 4.1 4.3  Table 2. ANOVA of TO and TS in OSAS pts’ groups. TO (%)   Kruskal-Wallis test p = 0.89 Dunn's Multiple Comp. Test rank sum Significance Mild vs Moderate 1,098 Ns Mild vs Severe 5,313 Ns Moderate vs Severe 4,215 Ns TS (ms/RR)   Kruskal-Wallis test p = 0.02* Dunn's Multiple Comp. Test rank sum Significance Mild vs Moderate 16,86 Ns Mild vs Severe 28,29 * Moderate vs Severe 11,43 Ns Mild Moderate Severe-4-202TO [% ] Figure 2. TO values in OSAS groups. Abnormal values over TO=0% cutoff dotted line in grey area. 4. Discussion The study shows that OSAS severity is associated to decreased heart rate turbulence slope highlighting the following four novel findings. The first one is that HRT analysis has been proved as an appropriate technique for the autonomic balance evaluation in OSAS, being suitable in over 90% of patients with disease of varying degrees. The second is that VPC’s number showed differences in means non statistically significant at ANOVA test between the three groups, confirming in some way that the only traditional ECG holter analysis of cardiac arrhythmias in OSAS doesn’t allow to differently describe desease severity. The third is that, considering that most clinical studies reported cutoff normal values of TO<0% and TS>2.5 ms/RR [14], data indicate that the main BRS alterations do not appear in the early HRT phase triggered by transient vagal inhibition, with TO<0 normal values in mild to severe pts., but during the slow one, due to the sympathetic hyperactivity affecting the heart rate recovery, with TS<2.5 abnormal values associated to increasing OSAS severity. But the forth and most interesting clinical finding is that (see Box&Whiskers plot in Figure 3, lines from the bottom upwards respectively at 10th, 25th, median, 75th and 90th percentile of the distributions), while the simple polysomnographic analysis would have equally stratified the risk inside mild to severe groups, abnormal TS values allows to identify about a 70% of severe OSAS patients at higher risk of sudden cardiac death, about  a 60% of moderate OSAS patients with greater probability to develop cardiovascular impairments, and also about a 50% of mild OSAS patients, normally not submitted to any medical treatment, with abnormalities in cardiac autonomic activity even in the absence of overt cardiac disease, suggesting, however, to start a therapy.  Mild Moderate Severe0.02.55.07.5TSc [ms/RR] Figure 3. TS values in OSAS groups. Abnormal values below TS=2.5 ms/RR cutoff dotted line in grey area 10095. Conclusion Although there is a well-known evidence of sympathetic nervous system increasing activity in patients with sleep-disordered breathing, the pathophysiological mechanisms leading to cardiovascular disease in OSAS are complex and still not fully understood. HRT analysis appeared as a suitable tool for the autonomic control assessment in OSAS patients and further studies need to deeply investigate HRT alterations implicated in patients with mild-to-severe OSA. Our study shows that nighttime heart rate turbulence slope decreasing is associated to rising OSAS severity. It may be therefore speculated that heart rate turbulence slope alterations may precede the development of cardiovascular disease in patients with OSAS. These findings support the conclusion that HRT assessment could have an in-time prognostic value related to the development of cardiovascular disease in OSAS [18,19], allowing to detect patients at greater probability of worsening, and stratifying their risk within the degree of OSAS severity.  References [1] Young Y, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230–1235. [2] He J, Krygier MH, Zorick FJ, Conway W, Roth T. Mortality and apnea index in obstructive sleep apnea. Experience in 385 patients. Chest 1988; 94: 9–14. [3] Porta A, D’Addio G, Maestri R, Pinna GD. Assessment of cardiovascular regulation through irreversibility analysis of heart period variability: a 24h Holter study in healthy and chronic heart failure populations. Phil Trans R Soc A 2009; 367, 1359–1375 doi:10.1098/rsta.2008.0265 [4] Cesarelli M, Romano M, Bifulco P, Improta G, D’Addio G. An application of symbolic dynamics for fhrv assessment. Stud Health Technol Inform ISSN 0926-9630  2012;180:123-7. [5] D’Addio G., Cesarelli M., Maestri R., G. Furgi , Ferrara N., Rengo F. Neurohormonal and functional correlates of linear and Poincarè plot indexes of heart rate variability in heart failure patients. Computing in Cardiology ISSN 0276-6574 2012; 39:937-940. [6] Accardo A, Cusenza M, De Felice A, D’Addio G. Ultradian Rhytms During Day and Night in Normal and COPD Subjects. Stud Health Technol Inform ISSN 0926-9630 2012;180:1120-2. [7] Corbi G, D'Addio G, Russo G, Rengo G, Pinna GD, Maestri R, Rengo F, Ferrara N. A non-linear analysis of heart rate variability in stroke patients. Mathematics and Computers in Contemporary Science, WSEAS Press 2013 ISBN: 978-1-61804-152-4. pp. 117-122 [8] Corbi G, Accardo A, Ferrara N, Cesarelli M, D’Addio G. Heart rate variability in noltisalis database: twenty-four-hour fractal dimension analysis. Recent advances in Biomedicine and Health Sciences WSEAS press ISSN: 1790-5125 pp.gg. 13-18. [9] Corbi G, Cesarelli M, Ferrara N, D’Addio G. Reproducibility of non linear analysis parameters in chronic heart failure patients. Recent advances in Biomedicine and Health Sciences WSEAS press ISSN: 1790-5125 pp.gg. 19-24. [10] Brown TE, Beightol LA, Koh J, Eckberg DL (1993) Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol 75:2310–2317 [11] Ryan S, Ward S, Heneghan C, McNicholas WT. Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. Chest 2007;131(4):1100-7. [12] La Rovere MT, Maestri R, Pinna GD, Sleight P, Febo O. Clinical and haemodynamic correlates of heart rate turbulence as a non-invasive index of baroreflex sensitivity in chronic heart failure. Clin Sci (Lond) 2011;121(6):279-84. [13] A Bauer, M Malik, G Schmidt, P Barthel, H Bonnemeier, I Cygankiewicz, P Guzik, F Lombardi, A Müller, A Oto, R Schneider, M Watanabe, D Wichterle, W Zareba. Heart rate turbulence: standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus. J Am Coll Cardiol 2008;21;52(17): 1353-65. [14] D'Addio G, Cesarelli M, Corbi G, Romano M, Furgi G, Ferrara N, Rengo F. Reproducibility of heart rate turbulence indexes in heart failure patients. Conf Proc IEEE Eng Med Biol Soc 2010;2010:2573-6. [15] Corbi G, D'Addio G, Ferrara N, Cesarelli M. Are they reproducible in heart failure patients? the heart rate turbulence indexes. Mathematics and Computers in Contemporary Science. WSEAS Press 2013 ISBN: 978-1-61804-152-4. pp. 123-128  [16] D'Addio G, Cesarelli M, Romano M, Furgi G, Ferrara N, Rengo F. Pre-ectopic vagal tone affects heart rate turbulence slope in heart failure. Computing in Cardiology 2012; 39:933-936. ISSN 0276-6574. [17] Hallstrom AP, Stein PK, Schneider R, Hodges M, Schmidt G, Ulm K. Structural relationships between measures based on heart beat intervals: potential for improved risk assessment. IEEE Trans Biomed Eng 2004;51(8):1414-20. [18] D'Addio G, De Felice A, Balzano G, Zotti R, Iannotti P, Bifulco P, Cesarelli M. Diagnostic decision support of heart rate turbulence in sleep apnea syndrome. Stud Health Technol Inform ISSN 0926-9630 2013;186:150-4. [19] Arpaia P,  Manna C,  Montenero G,  D'Addio G. In-Time Prognosis Based on Swarm Intelligence for Home-Care Monitoring: A Case Study on Pulmonary Disease. IEEE Sensors Journal 2012;12(3):692-698.    Address for correspondence.  Giovanni D’Addio Fondazione S. Maugeri IRCCS Via Bagni Vecchi 82037 Telese Terme (BN) Italy gianni.daddio@fsm.it 1010

OSAS severity is associated to decreased heart rate turbulence slope

37sSUNDAY, SEPTEMBER 8TH 2013in the management of pyopneumothorax with intercostal tube drainage only. The outcome of treatment was poor in the tubercular pyopneumothorax.52. Heart, blood and metabolism in sleep disordered breathingP307Effect of 3-month CPAP treatment on blood pressure and serum aldosterone concentration in patients with resistant hypertensionPatricia Lloberes1, Gabriel Sampol1, Eugenia Espinel2, Alfons Segarra2, M. Ferrer4, Odile Romero3, Maria Jose Jurado3, M. Antonia Ramon1, Dolores Untoria1, Miguel Angel Martinez Garcia5. 1Pneumology-Sleep Unit, Hospital Universitari Vall D’Hebron, Barcelona, Spain; 2Nephrology, Hospital Universitari Vall D’Hebron, Barcelona, Spain; 3Neurophysiology-Sleep Unit, Hospital Universitari Vall D’Hebron, Barcelona, Spain; 4Biochemistry, Hospital Universitari Vall D’Hebron, Barcelona, Spain; 5Pneumology, Hospital La Fe, Valencia, SpainIntroduction: The role of the renin-angiotensin-aldosterone system (RAAS) on the association obstructive sleep apnea (OSA) and resistant hypertension (RH) is unclear. Aim: To analyze the effect of CPAP on 24-h blood pressure monitoring (ABPM) and on serum aldosterone in RH patients. Methods: 102 patients with an OSA15 and of  ce-RH were randomized to CPAP (n=50) or to conventional treatment (n=52) for 3 months. 24-h ABPM and serum aldosterone were measured. 78 patients completed the follow-up (36 CPAP, 42 conventional treatment). Results: 66.7% were male, aged 58.27±9.3yrs and AHI 50.1±21.6, without signi  cant differences between both groups. Serum aldosterone and AHI correlated signi  cantly in patients with ABPM-con  rmed RH (r= 0.25, p=0.02). CPAP achieved a signi  cant decrease in serum aldosterone and 24-h BP decreased especially in those with ABPM-con  rmed RH.Effects of 3-month treatment on 24-h BP and serum aldosterone in patients with ABPM-con  rmed resistant hypertension, randomized to conventional treatment or to CPAPmmHg Baseline Conventional treatment p Baseline CPAP pDaytime SBP 142.6±12.39 141.92±15.88 0.76 143.16±12.12 137.8±13.3 0.03Daytime DBP 83.57±12.46 83.92±14.2 0.75 83.41±10.26 80.08±9.93 0.02Nighttime SBP 132.5±17 133.57±19.82 0.75 130.5±15.6 124.45±12.41 0.08Nighttime DBP 77.35±15.02 77.2±18.1 0.94 74.2±9.3 69.1±7.7 0.00724-h SBP 139.57±12.4 141.93±15.88 0.3 140.08±10.95 137.8±13.3 0.3124-h DBP 81.4±12.65 81.6±14.97 0.84 80.8±9.35 76.41±9.07 0.002Serum aldosterone (ng/dL)25.24±11.27 24.45±10.23 0.6 25.28±9.23 21.76±9.32 0.01Conclusion: The association between OSA and RH could be mediated at least in part by an effect on the RAAS.P308The effect of simulated obstructive hypopnea and apnea on thoracic aortic wall transmural pressuresChristian F. Clarenbach1, Giovanni Camen1, Noriane A. Sievi1, Christophe Wyss2, John R. Stradling3, Malcolm Kohler1. 1Sleep Disorders Centre and Pulmonary Division, University Hospital Zurich, Zurich, Switzerland; 2Division of Cardiology, University Hospital Zurich, Zurich, Switzerland; 3Oxford Center for Respiratory Medicine and Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United KingdomBackground: Preliminary evidence supports an association between OSA and thoracic aortic dilatation, although potential causative mechanisms are incompletely understood; these may include an increase in aortic wall transmural pressures, induced by obstructive apnoeas and hypopnoeas. Methods: In patients undergoing cardiac catheterization mean blood pressure (MBP) in the thoracic aorta and oesophageal pressure were simultaneously recorded by an indwelling aortic pigtail catheter and an oesophageal catheter in randomized order during: normal breathing, simulated obstructive hypopnoea (inspiration through a threshold load), simulated obstructive apnoea (Mueller manoeuvre), and end-expiratory central apnoea. Transmural aortic pressure (aortic MBP minus oesophageal pressure) was calculated as a measure of aortic wall stress. Results: 10 patients with a median age (range) of 64 (46-75) years were studied. Inspiration through a threshold load, Mueller manoeuvre and end-expiratory central apnoea were successfully performed and recorded in 10, 7 and 9 patients, respectively. The difference between aortic MBP and oesophageal pressure (and thus the extra aortic dilatory force) was median (quartiles) +9.3 (+5.4, +18.6) mmHg, p=0.02 during inspiration through a threshold load, +16.3 (+12.8, +19.4) mmHg, p=0.02 during the Mueller manoeuvre, and +0.4 (-4.5, +4.8) mmHg, p=0.80 during end-expiratory central apnoea.Conclusions: Simulated obstructive apnoea and hypopnoea increase aortic wall dilatory transmural pressures because intra-aortic pressures fall less than oesophageal pressures. Thus OSA may mechanically promote thoracic aortic dilatation.P309Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure - a randomized, controlled, double-blind, crossover trialThomas Bitter, Andrea Zwenke, Zisis Dimitriadis, Thomas Fischbach, Markus Möllenberg, Jelena Dohrmann, Christian Prinz, Maryam Afsah, Dieter Horstkotte, Olaf Oldenburg. Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, GermanyBackground: Studies con  rmed Cheyne-Stokes respiration (CSR) to be associated with elevated pulmonary capillary wedge pressure (PCWP) in chronic heart failure (CHF). This study aimed to investigate the acute effects of lowering PCWP and pulmonary artery pressure (PAP) on CSR severity.Methods: 21 consecutive patients with CHF and CSR (apnea-hypopnea-index (AHI 15/h)) underwent right heart catheterization, followed by infusion of glyceryltrinitrate (GTN), and inhalation of iloprost. Throughout the procedure PAP and PCWP was measured invasively. Afterwards maximum tolerable dosage of GTN and iloprost were randomly applied in 2 split-night procedures versus i.v. or inhalative NaCl 0.9% under full polysomnography monitoring.Results: Mean (m)PAP was signi  cantly reduced by GTN (20.1±9.0 to 11.6±4.2mmHg, p<0.001; infusion rate 6.2±1.5ml/h) and iloprost (16.9±7.9 to 14.2±6.4mmHg, p<0.01; dosage: 10 mcg/ml), whereas mPCWP was lowered exclusively by GTN (14.0±5.6 to 7.2±3.9 mmHg, p<0.001; iloprost: 11.7±6.2 to 11.0±6.3mmHg, p=n.s.). Compared to placebo sleep studies revealed no signi  cant improvement of AHI (GTN: 39.0±17.7/h vs. 35.3±16.0/h, p=n.s.; iloprost: 34.9±21.9/h vs. 33.3±19.4/h, p=n.s.) and central apnea index (GTN:14.4±16.5/h vs. 11.5±16.37h, p=n.s.; iloprost:11.0±16.3/h vs.12.5±19.1/h, p=n.s.) following GTN or iloprost treatment, respectively.Conclusion: GTN and Iloprost led to a signi  cant reduction in PAP, whereas PCWP was lowered by GTN exclusively. However, acute improvement of pulmonary congestion had no impact on CSR severity. Extended treatment periods appear crucial for successful causal therapies.P310OSAS severity is associated to decreased heart rate turbulence slopeAlberto De Felice1, Giovanni D’Addio1, Maria Romano2, Giovanni Balzano1, Mario Cesarelli2. 1Scientifi c Institute of Telese, S. Maugeri Foundation, Telese Terme, BN, Italy; 2DIBET, University Federico II, Naples, BN, ItalyObstructive sleep apnea syndrome (OSAS) has been associated to impaired barore  ex sensitivity (BRS) which has recently been shown to be non-invasively assessed by heart rate turbulence (HRT) analysis. Although HRT seems to be better suited than traditional heart rate variability indexes for autonomic assessment in presence of respiratory and arrhythmic disorders, very few papers addressed its evaluation in OSAS. Aim of the study is to  nd out whether and to which extend HRT is associated to OSAS severity. HRT consists of sinus cycle length  uctuations following spontaneous isolated VPC composed by an early rate acceleration phase, namely turbulence onset (TO), and by a late deceleration phase, namely turbulence slope (TS). We studied HRT in polysomnographic recordings of 82 mild (5<AHI<15), 74 moderate (16<AHI<30) and 65 severe (AHI>30) OSAS pts. (age 62±14, 71% males). Results showed that, while TO values did not signi  cantly differ between mild (-0,78±1,50), moderate (-0,89±1,78) and severe (-0,70±1,28) pts., TS signi  cantly decreases (Kruskal-Wallis P value <0.05) from mild (3,27±2,7) to moderate (2,6±2,6) and severe (1,98±2,5) pts., with a signi  cant Dunn’s multiple comparisons post test only between mild vs. severe OSAS pts. Data indicate that the main BRS alterations do not appear in the early HRT phase triggered by transient vagal inhibition, with TO<0 normal values in mild to severe pts., but during the slow one, due to the sympathetic hyperactivity affecting the heart rate recovery, with TS<2.5 abnormal values associated to increasing OSAS severity. These  ndings support the conclusion that HRT assessment could have a prognostic value related to the development of cardiovascular disease in OSAS.

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OSAS severity is associated to decreased heart rate turbulence slope

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Archivio della ricerca - Università degli studi di Napoli Federico II

Archivio della ricerca - Università degli studi di Napoli Federico II