Ipertensione Polmonare nel Gruppo 2
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Transcript of Ipertensione Polmonare nel Gruppo 2
Ipertensione polmonare nel gruppo 2Ipertensione polmonare nel gruppo 2
Rita Camporotondo Rita Camporotondo
Divisione di CardiologiaDivisione di Cardiologia
Fondazione IRCCS Policlinico S Matteo, PaviaFondazione IRCCS Policlinico S Matteo, Pavia
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
• Prevalence of PH depends on the population studied:
in referral centers about 2/3 of pts evaluated for potential heart transplant listing has PH.
PH in systolic dysfunction of the left ventriclePH in systolic dysfunction of the left ventricle
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
1.1. Pathophysiology of PH in LV systolic Pathophysiology of PH in LV systolic dysfunction. dysfunction.
2. Clinical implications of PH.
3. Treatment of PH.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Pathophysiology of PH in LV systolic dysfunction: Pathophysiology of PH in LV systolic dysfunction: backward transmission of high filling pressure. backward transmission of high filling pressure.
1000 HF pts undergoing transplant evaluation
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Drazner MH, J Heart Lung Transplant 1999
• Capomolla S. J Heart Lung Transplant 2000
• 259 HF pts
DT, Pulmonary venous flow,DT, Pulmonary venous flow,
Left atrial function at echoLeft atrial function at echo
was the strongest predictor
of sPA in pts with/without mitral regurgitation
• Sarano ME. JACC 1997
• 102 HF pts
PH not related to EF but strongly related to degree of degree of mitral regurgitation and mitral regurgitation and DTDT
Pathophysiology of PH in LV systolic dysfunction: Pathophysiology of PH in LV systolic dysfunction: backward transmission of high filling pressure. backward transmission of high filling pressure.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
46 HF pts, LVEF <30%, baseline and exercise Doppler echo46 HF pts, LVEF <30%, baseline and exercise Doppler echo
<Independent predictors of PASP at rest were left atrial volume <Independent predictors of PASP at rest were left atrial volume (p=0.006), E wave velocity (p=0.02), mitral tenting area (p=0.005)(p=0.006), E wave velocity (p=0.02), mitral tenting area (p=0.005)
and mitral effective regurgitant orifice (ERO) (p=0.02)….and mitral effective regurgitant orifice (ERO) (p=0.02)….
..A larger rise in mitral regurgitant volume during exercise emerged..A larger rise in mitral regurgitant volume during exercise emergedas the single determinant of exercise induced increase in PASP>as the single determinant of exercise induced increase in PASP>
Cody RJ, Circulation 1992
EndothelinEndothelin plasma levels correlate with PH in HF pts
Dupuis J, Circulation 1996EndothelinEndothelin spill over in the
lungs correlates with PVR in HF pts
Cooper CJ, Am J Cardiol, 1998
L-NMMA (NONO inhibitor) 6 controls, 9 HF + normal PVRI,9 HF+ ↑ PVRI.Response to L-NMMA was less
in pts with HF and hight PVRI. Impaired endothelial NO function
Pathophysiology of PH in LV systolic dysfunction: Pathophysiology of PH in LV systolic dysfunction: reactive increase in resistances.reactive increase in resistances.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
1.1. Pathophysiology of PH in LV systolic Pathophysiology of PH in LV systolic dysfunction. dysfunction.
2. Clinical implications of PH.
3. Treatment of PH.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Clinical implications:Clinical implications:reduced exercise tolerance in HF pts. reduced exercise tolerance in HF pts.
• It is NOT PH “per se”, rather it is the right ventricular dysfunction determined by PH to reduce the exercise tolerance.
Butler J, JACC 1999
320 HF pts: ex testing + RHC
High PVR = low peak VO2
A substantial proportion of pts decreased PCWP and increase RAP during exercise, indicating RV failure RV failure
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Cappola TP, Circulation 2002
1134 pts with CM undergoing RHCreferred to John Hopkins for hearttransplant evaluation.
mPAmPA was the most important hemo.risk factor. MyocarditisMyocarditis pts also were at higherrisk (acute PH, RV failure).
Clinical implications:Clinical implications:poor prognosis in HF pts. poor prognosis in HF pts.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
r=0.63
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
months0 20 40 60
0.00
0.25
0.50
0.75
1.00TAPSE>14
mm
TAPSE<=14mm
141 pts, DCM/IHD, EF<35%
End point: death or urgent transplantation
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
• Costard-Jackle A et al. JACC 1992; 19:48
• PVR >2.5 vs ≤2.5 UW: mortalità a 3 mesi 17.9 vs 6.9%17.9 vs 6.9%
• PVR >2.5; PVR post NTP ≤2.5 UW con PA >85 mmHg: mortalità a 3 mesi 3.8%3.8%
• PVR >2.5; PVR post NTP >2.5 UW con PA ≤ 85 mmHg: mortalità a 3 mesi 40.6%40.6%
Clinical implications:Clinical implications:high risk for heart transplantation. high risk for heart transplantation.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
HETEROTOPIC Heart TransplantHETEROTOPIC Heart Transplant
The recipient right ventricle is already “adapted to PH”.The recipient right ventricle is already “adapted to PH”.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
1.1. Pathophysiology of PH in LV systolic Pathophysiology of PH in LV systolic dysfunction. dysfunction.
2. Clinical implications of PH.
3. Treatment of PH.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Treatment of PH in HF pts.Treatment of PH in HF pts.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
PAH therapy in HF pts.PAH therapy in HF pts.
• FIRST trial. Califf et al, AHJ 1997; 134:1
471 “severe CHF” pts assigned to epoprostenol or standard care
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
PAH therapy in HF pts.PAH therapy in HF pts.
• ENABLE 1 & 2. Results presented at 51st ACC meeting (2002)
1613 pts recruited at 151 centers, randomized to placebo or bosentan (125mg x 2)
Results:
1. No effects on death.
2. Early risk of increased hospitalizations.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Conventional treatment of PH in HF pts.Conventional treatment of PH in HF pts.
Capomolla S. Eur J Heart Failure 2000; 3:601
113 advanced HF pts assigned to intermittent dobutamine or nitroprusside
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Il nitroprussiato riduce• le pressioni di riempimento biventricolari
• la pressione polmonare
• le RVP
e aumenta la portata cardiaca
““Conventional” treatment of PH in HF pts.Conventional” treatment of PH in HF pts.
Etz CD Ann Thor Surg 07
10 HF pts with refractory PH undergoing LVAD implantation.
Mean f-up 6 months
Significant decrease of PAP and PVR
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Lewis GD, Circulation 2007; 116: 1555-62
• 34 HF pts with HF and PH randomized to 12 weeks sildenafilsildenafil (25-75 mg tid or placebo)
• Pts underwent CP test, RHC, first pass radionuclide ventriculography, 6MWT, QOL
Treatment of PH in HF pts. Future perspectives?Treatment of PH in HF pts. Future perspectives?
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Treatment of PH in HF pts. Future perspectives?Treatment of PH in HF pts. Future perspectives?
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Trial multicentrico internazionale attualmente in corso
• Therapy for right ventricular dysfunction!
Treatment of PH in HF pts. Treatment of PH in HF pts. Future perspectives ???Future perspectives ???
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Targeted metabolic modulation by dichloroacetate acutely improves RV inotropy in the ex vivo perfused heart
Treatment of PH in HF pts. Treatment of PH in HF pts. Take home messageTake home message
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011
Ipertensione polmonare nel gruppo 2:Ipertensione polmonare nel gruppo 2:
-É frequente nei pz con scompenso avanzato.
-Si associa a scarsa tolleranza allo sforzo ed a prognosi scadente.
- Richiede terapia medica aggressiva convenzionale ed approccio trapiantologico specifico.
Corso di aggiornamento sull’ Ipertensione Polmonare. Pavia, 20-21 Maggio 2011