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Scompenso cardiaco e sindromi correlate: non trascuriamo lo sleep disorder Michele Emdin, Claudio Passino U.O. Medicina Cardiovascolare Fondazione Toscana.

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Presentazione sul tema: "Scompenso cardiaco e sindromi correlate: non trascuriamo lo sleep disorder Michele Emdin, Claudio Passino U.O. Medicina Cardiovascolare Fondazione Toscana."— Transcript della presentazione:

1 Scompenso cardiaco e sindromi correlate: non trascuriamo lo sleep disorder Michele Emdin, Claudio Passino U.O. Medicina Cardiovascolare Fondazione Toscana Gabriele Monasterio Istituto di Fisiologia Clinica CNR, Pisa Scuola Superiore SantAnna Congresso tosco-umbro FIC Montecatini Terme, 14 novembre 2007

2 Cheyne, J. A case of Apoplexy, in Which the Fleshy Part of the Heart Was Converted into Fat. Dublin Hospital Reports, 1818, II, 216. …For several days his breathing was irregular; it would entirely cease for a quarter of minute, then it would become perceptible, though very low, then by degrees it became heaving and quick, and then it would gradually cease again: this revolution in the state of his breathing occupied about a minute during which there were about thirty acts of respiration... Stokes, W. Observations on some Cases of permanently slow Pulse. Dublin Quart. Jour. Med. Sc.,1846,II,83. …Then a very feeble, indeed barely perceptible inspiration would take place, followed by another somewhat stronger, until at length high heaving, and even violent breathing was established, which would then subside till the next period of suspension… This was frequently a quarter of minute in duration. I have little doubt that this was a case of weakened and probably fatty heart, with disease of the aorta… …of a patient with probable cardiac asthma: 60 sec sec.

3 POLYSOMNOGRAPHY

4 Cincinnati 2005 Grenoble 1999 Creteil 1994 Melbourne 1999 Toronto 1999 * prospective # retrospective Chronic heart failure: PREVALENCE of Cheyne-Stokes Respiration and Obstructive Apneas % 100* 34 * 20*450#75 * NB OA CSR

5 679 patients 5 studies NB OA CSR 44% 56% 16% 40% AB Chronic heart failure: PREVALENCE of Cheyne-Stokes Respiration and Obstructive Apneas

6 ** Javaheri S Ital. Circulation : 2154 Minutes * Sleep characteristics - 81 HF patients

7 Javaheri S Ital. Circulation : 2154 Sleep characteristics - 81 HF patients Arousal/hSleep efficiency

8 Andamento temporale su unepoca di 12 min della potenza dellEEG nelle bande caratteristiche in un soggetto con scompenso cardiaco senza respiro di Cheyne-Stokes. Andamento temporale su unepoca di 12 min della potenza dellEEG nelle bande caratteristiche in un soggetto con scompenso cardiaco con respiro di Cheyne-Stokes.

9 Analisi tramite algoritmo GSTFT Rappresentazione tempo-frequenza del segnale EEG (C4 –A1) in un soggetto con scompenso cardiaco e respiro di Cheyne-Stokes

10 METODI REGISTRAZIONE CARDIORESPIRATORIA BREVE CHF patient

11 Prevalence in previous studies: - Mortara et al, Circulation 1997: CSR/PB - 64% pts - Ponikowski et al, Circulation 1999: CSR/PB - 66% pts Prevalence of day-time CSR/PB: Pisa CSR/PB - 85 pts CSR/PB + 65 pts 57% 43%

12 REGISTRAZIONE CARDIORESPIRATORIA AMBULATORIALE METODI

13 REGISTRAZIONE CARDIORESPIRATORIA AMBULATORIALE

14 Effetti clinici del respiro di CS Cicli di desaturazione arteriosa »Ipossia disfunzione dorgano/danno endoteliale, vasocostrizione polmonare Iperattivazione simpatica »Diretta »Indiretta in risposta allipossia Effetti emodinamici (prevalentemente indiretti) » FC, vasocostrizione Aumento del post-carico e del lavoro cardiaco Effetti sulla variabilità della FC e PA

15 Effetti clinici del respiro di CS

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19 LV DYSFUNCTION -NaH20retention–vasoconstriction arrhythmogenesis–tissue ischaemia dyspnoea oedema arrhythmias sudden death fatigue NEURO-HORMONAL IMBALANCE IN HEART FAILURE BNPANP systemactivation >>> - baroreflex ergo-chemoreflex -SympatheticRAA activation

20 Hanly PJ, Am J Resp Crit C M 1996;153:272 Cheyne-Stokes e Mortalità nello SCC 16 pazienti con SCC severo in fase di stabilità clinica età media 64 aa, FE < 35% CSR 9/16 (AHI 41± 17 vs 6 ± 5)

21 P Lanfranchi et al, Circulation 1999; 99:1435 Valore prognostico del CS notturno nello SCC 62 pz con FE < 35%, NYHA II-III

22 MT LA Rovere et al., Eur Heart J 2003; Valore prognostico RP/CS durante la veglia

23 60 sec p= AHI > 30 / hour AHI < 30 / hour months proportion surviving AHI = apnea-hypopnea index EOV AHI > 30 / hour + EOV Corrà, Circulation 2006 Cheyne-Stokes Respiration during exercise in CHF: impact on PROGNOSIS Exercise Recovery

24 Pathogenesis of CSR in CHF: hypotheses Central (?) Hypocapnic (?!) Instability loop (!) - increased chemosensitivity - prolonged circulation time

25 Ipotesi periferica- ipersensibilità chemocettoriale Variazioni di PaCO2 Risposta ventilatoria eccessiva PaCO2 sotto la soglia apneica Apnea PaCO2 Ripresa ventilazione

26 L/min % mmHg 0 6 TIME (min) ms Sa O2 PET CO2 Minute Ventilation RR interval Hypoxic Ventilatory Response

27 RR interval Minute Ventilation PET CO2 Sa O L/min % mmHg ms 0 6 TIME (min) Hypercapnic Ventilatory Response

28 Normal chemoreflex Increased HVR Prevalence of diurnal CSR (%) Increased HCVR Increased HVR+HCVR Nocturnal apnea-hypopnea index * Giannoni A, Emdin M, Poletti R, Bramanti F, Prontera C, Piepoli M, Passino C. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias. Clin Sci (Lond) Oct 26; [Epub ahead of print]

29 peakVO 2 VE/VCO 2 slope ** * ml/min/kg NBCS NBCS * p<0.05, ** p<0.01 Giannoni A, Emdin M, et al.. Clin Sci (Lond) Oct 26; [Epub ahead of print]

30 NorEPIBNP NT-proBNP pg/ml ** *** NBCS NBCS NBCS ** p<0.01, *** p<0.001 Giannoni A, Emdin M, et al.. Clin Sci (Lond) Oct 26; [Epub ahead of print]

31 Multivariate Analysis CO 2 -sensitivity and BNP level are independent predictors of CSR (also considering O 2 -sensitivity, peak VO 2, VE-VCO 2 slope, norepinephrine, NT-proBNP from univariate analysis)

32 Specificity Sensitivity AUC 0.89 P<0.001 AUC 0.93 P<0.001 CO 2 -sensitivity and BNP as predictors of CSR HCVR slope BNP

33 chemoceptors CSR Norepi BNP, ANP LV dysfunction altered haemodynamics hypoxia

34 LV DYSFUNCTION -NaH20retention–vasoconstriction arrhythmogenesis–tissue ischaemia dyspnoea oedema arrhythmias sudden death fatigue NEURO-HORMONAL IMBALANCE IN HEART FAILURE BNPANP systemactivation >>> - baroreflex ergo-chemoreflex -SympatheticRAA activation

35 60 sec. Why? To improve respiratory pattern To improve sleep quality/QOL To improve cardiac performance To improve prognosis (?) When? Which patient? Which marker (daytime abnormalities, PSG-AHI, BNP, …)? How? CSR in CHF: therapeutical target?

36 60 sec. Diagramma del trattamento del respiro di Cheyne Stokes nello scompenso cardiaco Scompenso cardiaco con respiro di Cheyne-Stokes Ottimizzare la terapia per CHF. (farmaci, CRT) Assenza di Cheyne-Stokes persiste Considerare un trattamento specifico (Trapianto Cardiaco) Metilxantine O2 terapiaCPAP o altri device

37 N Engl J Med 2005;353:

38 Grazie per lattenzione!

39 NYHA CLASS LVEF ** % NBCS NBCS * p<0.05 Giannoni A, Emdin M, et al.. Clin Sci (Lond) Oct 26; [Epub ahead of print]

40 Effect of Theophylline on Sleep-Disordered Breathing in Heart Failure S. Javaheri et al. NEJM August 22,1996 n8 335: Protocollo dello studio: 15 pz con scompenso cardiaco e disturbi della respirazione notturni (AHI > 10/ora). Somministrazione orale di Teofillina o placebo 2 volte die per 5 gg con una settimana di washout fra i due periodi. Risultati: Significativa riduzione degli episodi di apnea/ipopnea rispetto al placebo: Placebo Teofillina Possibili meccanismi della Teofillina: Competizione a livello centrale con il sito recettoriale dellAdenosina (depressore respiratorio) Incremento del deficit ventilatorio polmonare restrittivo associato allo scompenso cardiaco Effetto inotropo

41 Analisi tramite algoritmo GSTFT Rappresentazione tempo-frequenza del segnale EEG (C4 –A1) in un soggetto con scompenso cardiaco senza respiro di Cheyne-Stokes

42 Bi-level PAP may fit the abnormal breathing pattern of CSR-CSA better than CPAP. Therefore, bi-level PAP improves an abnormal breathing pattern more immediately and effectively than CPAP. In a recent study, it has been reported that 57% of patients showed no response to CPAP

43 Benefit of Atrial Pacing in Sleep Apnea Syndrome NEJM February 7, 2002 n 6, 346: Stephane Garrigue, M.D., Philippe Bordier, M.D., Pierre Jaïs, M.D., Dipen C. Shah, M.D., Meleze Hocini, M.D., Chantal Raherison, M.D., Manuel Tunon De Lara, M.D., Michel Haïssaguerre, M.D., and Jacques Clementy, M.D. 15 pz con OSA e PM bicamerale AHI in ritmo spontaneo: 28 AHI in ritmo elettroindotto 11 (P<0.001) PRO CONTRO

44

45 Increased long-term mortality in heart failure due to sleep apnoea is not yet proven T. Roebuck 1, P. Solin 1, D.M. Kaye 2,4, P. Bergin 2, M. Bailey 3 and M.T. Naughton 1 Eur Respir J May; 23: pazienti LVEF 19.9 ± 7.2% PCP 16.5 ± 8.3 mmHg CHF-N CHF-OSA CHF-CSA

46 Effetti clinici del respiro di CS Cicli di desaturazione arteriosa »Ipossia disfunzione dorgano/danno endoteliale, vasocostrizione polmonare Iperattivazione simpatica »Diretta »Indiretta in risposta allipossia Effetti emodinamici (prevalentemente indiretti) » FC, vasocostrizione

47 CO2 SENSITIVITY NEPI (pg/ml) R=0.322 P<0.05 Overall CO2 sensitivity vs adrenergic activation and ventilatory efficiency CO2 SENSITIVITY VE-VCO2 SLOPE R=0.549 P<

48 CO2 SENSITIVITY BNP (pg/ml) R=0.549 P< CO2 SENSITIVITY NT-proBNP (pg/ml) R=0.322 P<0.05 R=0.411 P<0.01 R=0.400 P<0.01 Overall CO2 sensitivity vs B-type Natriuretic Peptides

49 CSR is associated with: Enhanced chemoceptive sensitivity to O2 and CO2 Symptom severity and systolic dysfunction Functional capacity and ventilatory efficiency Adrenergic activation BNP/NT-proBNP levels CSR is predicted by: Enhanced chemoceptive sensitivity to CO2 BNP plasma level CONCLUSIONS


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