Cuore e polmone: l’ipertensione polmonare nelle malattie ... e polmone l... · Centro...
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Pulmonary Hypertension Unit La Sapienza University of Rome Carmine Dario Vizza Pulmonary Hypertension Unit Dept. Cardiovascular and Respiratory Diseases La Sapienza University of Rome e-mail : [email protected] Cuore e polmone: l’ipertensione polmonare nelle malattie respiratorie croniche ostruttive
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Transcript of Cuore e polmone: l’ipertensione polmonare nelle malattie ... e polmone l... · Centro...
Pulmonary Hypertension Unit
La Sapienza University of Rome
Carmine Dario Vizza Pulmonary Hypertension Unit
Dept. Cardiovascular and Respiratory Diseases
La Sapienza University of Rome
e-mail : [email protected]
Cuore e polmone: l’ipertensione polmonare
nelle malattie respiratorie croniche ostruttive
Pulmonary Hypertension Unit
La Sapienza University of Rome
Caratteristiche emodinamiche
del circolo polmonare
ART POLM ATRIO SIN
ARTERIE VENE CAPILLARI
16 mmHg 8 mmHg Normale
Pulmonary Hypertension Unit
La Sapienza University of Rome
Meccanismi di regolazione delle Resistenze
Vascolari Polmonari
Pulmonary Hypertension Unit
La Sapienza University of Rome Faller Clin Exp Pharm Physiol 1999
Risposta acuta
Ipossia
Meccanismo di compenso per
evitare V/Q mismatch
Vasocostrizione
ipossica
Pulmonary Hypertension Unit
La Sapienza University of Rome Faller Clin Exp Pharm Physiol 1999
Risposta cronica
Ipossia
Rimodellamento del vaso con persistente aumento
delle resistenze al flusso
Aumento espressione
geni ET-1, Ang II,
VEGF, PDGF….
Pulmonary Hypertension Unit
La Sapienza University of Rome
V/Q mismatch
Fisiopatologia della IP nella BPCO
Shear Stress
Vascular
remodelling Vasoconstriction Policitemia
Hypercapnia
Acidosis Hypoxia
Inflammation
Pulmonary Vascular
Resistance
Hyperinflation
Vessels loss
Pulmonary Hypertension Unit
La Sapienza University of Rome
Qual è la prevalenza e l’impatto della IP
nelle pneumopatie ?
Pulmonary Hypertension Unit
La Sapienza University of Rome
• 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
Pulmonary Hypertension Unit
La Sapienza University of Rome
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+0.8
EF RV (%) 41+9 45+9 40+10 26+13
Hemodynamic profile of lung Tx candidates
CD Vizza, Chest 1998; 113:576-83
Pulmonary Hypertension Unit
La Sapienza University of Rome
Pap distribution in COPD and CF patients
candidates to lung Tx
n=220
CD Vizza, Chest 1998; 113:576-83
PAPm, mmHg
% p
ts
Pulmonary Hypertension Unit
La Sapienza University of Rome
Correlazione tra FE VD e resistenze vascolari
polmonari
0
4
8
12
16
20
24
0 10 20 30 40 50 60 70 80
RV
PI,
Wood U
nits m
2
FE ventricolo destro, %
r = - 0.12
r = -0.78
Pulmonary Hypertension Unit
La Sapienza University of Rome
Prognostic role of pulmonary hypertension
Traver GA Am Rev Resp Dis 1979
Wietzenblum E Thorax 1981;36:752.
Finlay M. Eur J Resp Dis 1983;64:252.
Pulmonary hypertension is an independent factor influencing
the prognosis of patients with respiratory insufficiency
Andersen KR. J Heart Lung Transplant 2012;31:373–80
Pulmonary Hypertension Unit
La Sapienza University of Rome
L’ ipertensione polmonare severa o fuori
proporzione nella BPCO
Pulmonary Hypertension Unit
La Sapienza University of Rome Thabut G, Chest 2005
Pulmonary Hypertension Unit
La Sapienza University of Rome
Ipertensione polmonare “inappropriata”
Thabut G, Chest 2005
Pulmonary Hypertension Unit
La Sapienza University of Rome
Che tipo di vasculopatia polmonare
hanno questi pazienti ?
Pulmonary Hypertension Unit
La Sapienza University of Rome Carlsen J. JHLT 2013;32:347–354
Pulmonary Hypertension Unit
La Sapienza University of Rome Carlsen J. JHLT 2013;32:347–354
Moderate PH Severe PH IPAH
Hystological findings in COPD-PH
In patients with severe PH related COPD the
hystology is very similar to IPAH
Pulmonary Hypertension Unit
La Sapienza University of Rome
Possibilità terapeutiche ?
Pulmonary Hypertension Unit
La Sapienza University of Rome
Bosentan in COPD:
Stolz D. et al Eur Resp J 2008;32:619-628:
Pulmonary Hypertension Unit
La Sapienza University of Rome
Bosentan in COPD:
Changes in A-a O2 gradient
Stolz D. et al Eur Resp J 2008;32:619-628:
Changes in PaO2
PaO
2, m
mH
g
Placebo Bosentan
6MWT Treatment effect -10 m
Pulmonary Hypertension Unit
La Sapienza University of Rome
Tadalafil in COPD
Goudie AR. Lancet Respir Med 2014
Pulmonary Hypertension Unit
La Sapienza University of Rome
Tadalafil in COPD
Goudie AR. Lancet Respir Med 2014
Pulmonary Hypertension Unit
La Sapienza University of Rome
Tadalafil in COPD
Goudie AR. Lancet Respir Med 2014
Pulmonary Hypertension Unit
La Sapienza University of Rome
Possiamo aspettarci effetti positivi in
popolazioni con BPCO ma senza
ipertensione polmonare significativa ?
Pulmonary Hypertension Unit
La Sapienza University of Rome P Vitulo. J Heart Lung Transplant. 2017;36:166-174.
Pulmonary Hypertension Unit
La Sapienza University of Rome
Pulmonary Hypertension Unit
La Sapienza University of Rome
RHC
RHC
2
1
P Vitulo. J Heart Lung Transplant. 2017;36:166-174.
Pulmonary Hypertension Unit
La Sapienza University of Rome
Pulmonary Hypertension Unit
La Sapienza University of Rome
SPHERIC: primary end-point results
p=0.0317
67
89
10
11
Baseline Follow Up
Placebo Sildenafil
PVR adjusted prediction
p=0.0036
1.8
22
.22
.42
.62
.8
Baseline Follow Up
Placebo Sildenafil
CI adjusted prediction
Pulmonary Hypertension Unit
La Sapienza University of Rome
SPHERIC additional end-points results
P Vitulo. J Heart Lung Transplant. 2017;36:166-174.
Pulmonary Hypertension Unit
La Sapienza University of Rome
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
Pulmonary Hypertension Unit
La Sapienza University of Rome
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
Centro Ipertensione Polmonare
Primitiva e Forme Associate Responsabile Carmine Dario Vizza
PFTs-CPX Lab
Prof. Palange
Dott.Valli
CT & RNM Lab
Dott. Carbone
Dott. Francone
Reumathologists
Prof Valesini
Prof.Riccieri
Liver Transplant Unit
Prof. Rossi
Prof. Corradini
Lung Transplant Program
Prof.Coloni
Prof.Venuta
HIV clinic
Prof.Vullo
Echo Lab
Dr. Sciomer
Dr. Badagliacca
Right Cath Lab
Dott. Mancone
Dott. Stio
Pulmonologists
Prof. Parola
Pulmonary Hypertension Unit
La Sapienza University of Rome Thabut G, Chest 2005
Pulmonary Hypertension Unit
La Sapienza University of Rome
Ipertensione polmonare “inappropriata”
Thabut G, Chest 2005
Pulmonary Hypertension Unit
La Sapienza University of Rome
Inhaled Iloprost
Hypothesis
Pulmonary selectivity (no effects on systemic circulation)
Intra-pulmonary selectivity (effect only in well-ventilated
alveolar unit = no V/Q mismatch
Pulmonary Hypertension Unit
La Sapienza University of Rome H Olschewski, et al Am. J. Respir. Crit. Care Med., 1999
Patients with PH secondary to IPF: Hemodynamic effects
of iNO, parenteral and inhaled PGI2
Pulmonary Hypertension Unit
La Sapienza University of Rome
H OLSCHEWSKI, et al
Am. J. Respir. Crit. Care Med., 1999
Patients with PH secondary to IPF: Shunt and PaO2
Pulmonary Hypertension Unit
La Sapienza University of Rome
Sildenafil in PH secondary to pulmonary fibrosis
Ghofrani A. Lancet 2002
iNO
Epo
Sil
This pattern of results (iNO and Sild) represents the typical
profile of a selective pulmonary vasodilator
Pulmonary Hypertension Unit
La Sapienza University of Rome
Gas exchange and shunt
Ghofrani A. Lancet 2002
iNO
Epo
Sil
.. 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.
Pulmonary Hypertension Unit
La Sapienza University of Rome
Sildenafil in Patients with Lung Disease • 4 COPD and 3 IPF patients (5 on LTOT)
• 8 weeks sildenafil 50 mg t.i.d
Pre sildenafil Post sildenafil p
6MWT 80 (30–210) 120 (30–312) 0.0313
Estimated PAPs 65 (30–74) 55 (30–73) 0.0313
PCWP 16 (4–22) 12 (6–21) 0.6875
Mean PAP 39 (26–50) 34 (18–47) 0.1563
CO 4 (3–6.3) 4.8 (3.6–6.5) 0.4375
CI 2.4 (1.75–3.89) 2.76 (2.1–4.08) 0.4375
PVR 3.5 (2.9–13) 4.4 (2.5–9.7) 0.1563
PVRI 562(349–1782) 637 (313–1333) 0.1563
Madden. B et al. Vasc Pharm 2006; 44, 372 - 376
Pulmonary Hypertension Unit
La Sapienza University of Rome
Pulmonary Hypertension Unit
La Sapienza University of Rome
PA
Pm
, m
mH
g
CO, l/min
0,7 l/m
Modified from Holverda S. et al Pulm Pharm Therap 2008; 21: 558-564
Pulmonary Hypertension Unit
La Sapienza University of Rome Blanco I. Am J Respir Crit Care Med 2010; 181: 270–278
Pulmonary Hypertension Unit
La Sapienza University of Rome
Acute hemodynamic effect
Blanco I. Am J Respir Crit Care Med 2010; 181: 270–278
Pulmonary Hypertension Unit
La Sapienza University of Rome
Acute effect: PaO2, V/Q
Blanco I. Am J Respir Crit Care Med 2010; 181: 270–278
Pulmonary Hypertension Unit
La Sapienza University of Rome
Acute effect: Spirometry
Blanco I. Am J Respir Crit Care Med 2010; 181: 270–278
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