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Roberto Poscia

La Terapia dell ’ Ipertensione Polmonare associata a Pneumopatie. Roberto Poscia Pulmonary Hypertension Unit Dept. Cardiovascular and Respiratory Diseases La Sapienza University of Rome Responsabile Scientifico Clinical trial Center Az. Policlinico Umberto I

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Roberto Poscia

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  1. La Terapia dell’Ipertensione Polmonare associata a Pneumopatie Roberto Poscia Pulmonary Hypertension UnitDept. Cardiovascular and Respiratory DiseasesLa Sapienza University of Rome ResponsabileScientifico Clinical trial Center Az. Policlinico Umberto I e-mail : roberto.poscia@uniroma1.it

  2. Patologie Respiratorie e Patologie cardiovascolari: fattori di rischio condivisi Fumo Patologie Respiratorie IMPATTO DELLA PATOLOGIA RESPIRATORIA SUL CUORE INDIPENDENTEMENTE DALLE COMORBIDITA’ Obesità Età Patologie Cardiovascolari Dislipidemia Ipertensione Diabete

  3. Caratteristiche emodinamiche del circolo polmonare CAPILLARI ARTERIE VENE ART POLM ATRIO SIN Normale 16 mmHg 8 mmHg

  4. Ipossia Risposta acuta Vasocostrizione ipossica Meccanismo di compenso per evitare V/Q mismatch Faller Clin Exp Pharm Physiol 1999

  5. Ipossia Risposta cronica Aumento espressione geni ET-1, Ang II, VEGF, PDGF…. Rimodellamento del vaso con persistente aumento delle resistenze al flusso Faller Clin Exp Pharm Physiol 1999

  6. Fisiopatologia della IP nella BPCO V/Q mismatch Inflammation Shear Stress HypercapniaAcidosis Hypoxia Hyperinflation Vascular remodelling Vasoconstriction Policitemia  Pulmonary Vascular Resistance Vessels loss

  7. Qual è la prevalenza e l’impatto della IP nelle pneumopatie ?

  8. Omogeneita’ della casistica (soggetti con insufficienza respiratoria terminale, candidati a trapianto polmonare) • Numerosita’ adeguata del campione • Completezza dei dati • Emodinamica • Funzione Ventricolare destra • Funzione Respiratoria • Emogasanalisi

  9. Hemodynamic profile of lung Tx candidates CF COPD ILD PPH n=64 n=156 n=77 n=50 Pra (mmHg) 5+4 8+4 8+5 11+6 Pap (mmHg) 28+8 25+6 34+9 62+21 PVRi(WU /m2) 4.6+2.3 4.4+2 8+5 24+11 CI (L/min/m2) 4+0.7 3.1+0.7 3+0.6 2.4+0.8EF RV (%) 41+9 45+9 40+10 26+13 CD Vizza, Chest 1998; 113:576-83

  10. Pap distribution in COPD and CF patients candidates to lung Tx n=220 % pts PAPm, mmHg CD Vizza, Chest 1998; 113:576-83

  11. Correlazione tra FE VD e resistenze vascolari polmonari 24 r = -0.78 20 16 RVPI, Wood Units m2 12 8 r = - 0.12 4 0 0 10 20 30 40 50 60 70 80 FE ventricolo destro, %

  12. Prognostic role of pulmonary hypertension Pulmonary hypertension is an independent factor influencing the prognosis of patients with respiratory insufficiency Traver GA Am Rev Resp Dis 1979 Wietzenblum E Thorax 1981;36:752. Finlay M. Eur J Resp Dis 1983;64:252. Andersen KR. J Heart Lung Transplant 2012;31:373–80

  13. L’ ipertensione polmonare severa o fuori proporzione nella BPCO

  14. Thabut G, Chest 2005

  15. Ipertensione polmonare “inappropriata” Thabut G, Chest 2005

  16. Che tipo di vasculopatia polmonare hanno questi pazienti ?

  17. Carlsen J. JHLT2013;32:347–354

  18. Hystological findings in COPD-PH Moderate PH Severe PH IPAH In patients with severe PH related COPD the hystology is very similar to IPAH Carlsen J. JHLT2013;32:347–354

  19. Possibilità terapeutiche ?

  20. Bosentan in COPD: Stolz D. et al Eur Resp J 2008;32:619-628:

  21. Bosentan in COPD: Bosentan Placebo 6MWT Treatment effect -10 m Changes in PaO2 Changes in A-a O2 gradient PaO2, mmHg Stolz D. et al Eur Resp J 2008;32:619-628:

  22. Tadalafil in COPD Popolazione Omogenea Goudie AR. Lancet Respir Med 2014

  23. Tadalafil in COPD Goudie AR. Lancet Respir Med 2014

  24. Tadalafil in COPD Goudie AR. Lancet Respir Med 2014

  25. P Vitulo. J Heart Lung Transplant. 2017;36:166-174.

  26. RHC RHC 2 1 P Vitulo. J Heart Lung Transplant. 2017;36:166-174.

  27. SPHERIC: primary end-point results

  28. SPHERIC additional end-points results .. Sildenafil does not act as a non-specific vasodilator, but rather amplifies local vasoregulatory mechanisms in the pulmonary circulation. …. regional nitric oxide generation in the alveolo-capillary unit drops sharply during hypoxia and increases on alveolar re-oxygenation, as part of the hypoxic vasoconstrictor/normoxic vasodilator mechanism … Enhancement of the effect of locally generated nitric oxide by sildenafil might cause an overall decrease in pulmonary vascular resistace while maintaining ventilation/perfusion matching. P Vitulo. J Heart Lung Transplant. 2017;36:166-174.

  29. Conclusioni • L’ipertensione polmonare è un fattore prognostico indipendente nei pazienti con BPCO in fase di stabilità • Nel 5-6% dei casi l’ipertensione è severa • In questi pazienti le lesioni istopatologiche sono simili a quelle della ipertensione arteriosa polmonare • Iniziali esperienze suggeriscono l’efficacia emodinamica della terapia con Sildenafil

  30. Epilogo

  31. PFTs-CPX Lab Prof. Palange Dott.Valli CT & RNM Lab Dott. Carbone Dott. Francone Right Cath Lab Dott. Mancone Dott. Stio Echo Lab Dr. Sciomer Dr. Badagliacca Liver Transplant Unit Prof. Rossi Prof. Corradini HIV clinic Prof.Vullo Reumathologists Prof Valesini Prof.Riccieri Lung Transplant Program Prof.Coloni Prof.Venuta Pulmonologists Prof. Parola Centro Ipertensione PolmonarePrimitiva e Forme AssociateResponsabile Prof. Carmine Dario Vizza PH clinicians (Cardiology ward, CCU, consultation & outpatients management): Senior Cardiologists Pr. Vizza, Badagliacca, Dr. Poscia Fellows: Dr. Pezzuto, Dr.Papa In Training: Dr Pesce, Dr. Manzi

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