A rare case of porto-pulmonary hypertensionstatic.livemedia.gr/hcs2/documents/al15205_us41...TAPSE...
Transcript of A rare case of porto-pulmonary hypertensionstatic.livemedia.gr/hcs2/documents/al15205_us41...TAPSE...
Αριστοτέλειο Πανεπιστήμιο ΘεσσαλονίκηςΑ΄ Καρδιολογική Κλινική ΑΧΕΠΑ Διακλινικό Ιατρείο Πνευμονικής Υπέρτασης
03/04/15
A rare case of porto-pulmonary hypertension
Sophia Anastasia Mouratoglou
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Received:Travel fees from ACTELIONResearch funding from United Therapeutics
Disclosures
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!Female!DoB: 17/11/1968, 47y
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!2008! Autoimmune hepatitis! Liver cirrhosis! Smoker, history of mild asthma
!2009! episode of acute PE, anticoagulation for 6
months
Background
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!2010! Portal hypertension (splenomegaly,
thrombocytopenia, mild oesophageal varices)! Portal thrombosis
!Hepatology assessment! Child-Pugh class B cirrhosis ! MELD score 12
Background
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MELD score
• MELD =(0.957 x LN(creatinine) + 0.378 x LN(bilirubin) +1.12 x LN(INR) +0.643) x 10
Capped at 40
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• Azathioprine 2mg/kg• Propranolol 40 mg tid• LMWH
Medications
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!2010:
! shortness of breath on exertion, fatigue! no syncope! no chest pain
Background
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!ABG on room air" pH 7.41, PO2 56mmHg, PCO2 37mmHg, A-a
gradient 35mmHg
!PFTs" DLCO 70% predicted, mild obstruction and
restriction
!HRCT and CT pulmonary angio" mild enlargement of some distal pulmonary
arterioles and areas of nontapering pulmonary vessels. No pulmonary thrombosis
Diagnostic tests
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6MWT
Pre Post
SpO2 (%) 96 81
HR (bpm) 55 105
Borg score 1 6
Total walked distance: 471mTotal walked distance: 471mTotal walked distance: 471m
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"No signs of significant LV systolic or diastolic dysfunction
"No RV dilatation
"RVSP = 39 mmHg
Echo
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Bubble echo
Cycle 0
Cycle 0
Cycle 6
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Bubble echo
Cycle 0
Cycle 0
Cycle 6
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Bubble echo
Cycle 0
Cycle 0
Cycle 6
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1. room air pO2 <80mmHg or A-a gradient >15mmHg
2. evidence of intrapulmonary shunting (typically on contrast-enhanced echocardiography or a lung perfusion scan)
3. portal hypertension with or without cirrhosis
Hepatopulmonary syndrome (HPS): Definition
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!1 liter of supplemental oxygen per minute at rest and 3 liters per minute (L/min) with exertion
Management - Supplemental oxygen
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!Improved gradually with oxygen therapy
!Patient was placed on the liver transplant list with a MELD exception for HPS
Clinical course
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" Dyspnoea in mild exertion since 6months" NYHA 3" BMI: 28kg/cm2
" SAT 96%, no clubbing" HR 65/min, " BP 120/80mmHg" Loud P2" No ascites/ mild peripheral edema" Palpable liver/spleen
Current condition
6MWT (without oxygen)6MWT (without oxygen)6MWT (without oxygen)Pre Post
SpO2 96 87HF 63 111Borg 0 6Total walked distance 452 mTotal walked distance 452 mTotal walked distance 452 m
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! Mild RV dilatation! TAPSE 2.3cm! RVSP 85mmHg! Mild pericardial effusion
Echo
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• ECG: SR, no RVH• LFTs: DLCO 55% predicted• HRCT: No lung disease• Lung perfusion scan: Negative for proximal
CTEPH, can’t rule out distal subsegmental disease
• Normal immunologic tests
Diagnostic tests
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!Child-Pugh class B!MELD score 15
Hepatology workup
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Hb: 13 g/dl, HR: 69/minBSA: 1.85m2
BaselineBaseline
Pressure (mmHg) SAT (%)
RA 7RV 78/7PA 77/31/46 75.5PAWP 10Ao 120/70 96.8PVR (Wood) 6.76.7PVRi (Woodxm2) 12.412.4CI (L/min/m2) 2.912.91Pulmonary angiography: No signs of CTEPHPulmonary angiography: No signs of CTEPHPulmonary angiography: No signs of CTEPH
RHC - indirect Fick
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Pulmonary angiogram
Negative for CTEPH
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Pulmonary angiogram
Negative for CTEPH
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Pulmonary angiogram
Negative for CTEPH
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ERS Task Force Pulmonary-Hepatic Vascular Disorders Scientific Committee Guidelines for PoPH candidates for OLT
Rodriguez-Roisin R et al. Eur Respir J 2004
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!Withdrawn from liver transplant list
!Start bosentan (upitrated to 125 mg BID) with close LFT monitoring.
!Discontinued propranolol (prim. prevention)
Therapy
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!Clinical improvement!NYHA 2!6MWT 536m!Does not need supplemental oxygen
therapy
!Echo: borderline RV size and normal systolic function
6 months later – clinical assessment
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Hb: 11.5 g/dl, HR: 77/minBSA: 1.8m2
BaselineBaseline 6 months post treatment
6 months post treatment
Pressure (mmHg) SAT (%) Pressure
(mmHg) SAT (%)
RA 7 9RV 78/7 67/19PA 77/31/46 75.5 67/36/49 78PAWP 10 10Ao 120/70 96.8 120/70 98PVR (Wood) 6.76.7 3.983.98PVRi (Woodxm2) 12.412.4 7.27.2CI (L/min/m2) 2.912.91 5.55.5
At 6 monthsrepeat RHC - thermodilution
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1. targeted therapy with ERA2. b-blocker cessation3. both
Significant CI increase could be attributed to
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" All patients (n=10) were free of PAH targeted therapies" 28% increase in cardiac output with no change in mean pulmonary
artery pressure, resulting in a 19% decrease in pulmonary vascular resistance
β-blocker cessation in PoPH
Provencher et al. Gastroenterology 2006
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n=34 consecutive patients with PoPH treated with first-line bosentanShort-term evaluation was performed after 5±2 months after bosentan initiation
Targeted PAH therapy with bosentan
Savale et al. ERJ 2013
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Treatment goals
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Treatment goals
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Treatment goals
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Treatment goals
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Treatment goals
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Treatment goals
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Epidemiology
! 0.73% in autopsy series! 2-5% amongst pt with liver
cirrhosis! 3.5-8.5% amongst pt in LT lists! Liver transplant recipients
2.5-4%
! ≈ 9% of all Group 1 PH patients
! Diagnosis of PoPAH# 4-7y after portal hypertension
! Risk of PoPAH increases with portal hypertension duration
" Portopulmonary Hypertension
" Risk factors: Autoimmune etiology and female sex
" Independent of the severity of the liver disease
" Prognosis is related to the severity of cirrhosis and to
Budhiraja R et al, CHEST 2003Hoeper M, Lancet 2004
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!Untreated or treated, if mean PAP>50mmHg peri-transplant mortality is well over 50%
!If mean PAP is 35-50mmHg and PVR greater than 250dynes, mortality 50%
!Consensus goals of PAH therapy in PoPH:! Mean PAP less than 35mmHg
Portopulmonary Hypertension and liver transplantation
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" HPS should be suspected in symptomatic patients with portal hypertension who present with desaturation at rest or during exercise
" HPS and PoPH are clinically distinct entities with seemingly distinct pathophysiologies, but they can very rarely occur simultaneously or sequentially in the same patient
" The effect of PAH targeted therapies in PoPH seem to be similar to those observed in other forms of PAH
" Β-blockers should be discontinued when possible in patients with PoPH
Take home messages
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Αριστοτέλειο Πανεπιστήμιο ΘεσσαλονίκηςΑ΄ Καρδιολογική Κλινική ΑΧΕΠΑ Διακλινικό Ιατρείο Πνευμονικής Υπέρτασης
03/04/15
Thank you!!
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Back up slides
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!10–30% of patients referred for LTx evaluation and only 1% of patients with chronic liver disease in the non-transplant setting (Deibert 2006)
!Dilatation at both the pre- and capillary level of the pulmonary circulation, especially in the lower lobes
Hepatopulmonary syndrome: Characteristics
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Baseline (Fick) after 6 months (TD)
6MWT (m) 452 536PA (mmHg)PVR (W)CI (L/min/m2)
77/31/m466.72.9
67/36/m493.95.5
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!PoPH patients are usually excluded from RCTs with PAH-specific therapies
RCTs on medical therapy
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1. Add a PDE-5 inhibitor2. Do nothing3. Repeat the RHC using the indirect Fick
method
How would you proceed with this patient?
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Hepatic venous pressure gradient
Ripoll et al, Gastroenterology 2007 Ripoll et al, Hepatology, 2005
HVPG >12 mmHg Severe portal hypertension
HVPG>10mmHg
HVPG<10mmHg
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Targeted PAH therapy with ambrisentan
Cartin-Ceba et al. Chest 2011
n=17 patients with PoPH treated with ambrisenten monotherapy
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The short-term haemodynamic response was significantly better in patients with C-P class B cirrhosis compared with those with C-P class A cirrhosis or with noncirrhotic portal hypertension
Hemodynamic improve is not related to the severity of the liver disease
Savale et al. ERJ 2013
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1-3 per million population(Humbert 2006)
Cirrhosis <1%(Mc Donnell 1983)
Portal Hypertension 2-3%(Hadengue 1991, Yang 2000)
Liver transplant candidates 6-8.5%(Colle 2003, Ramsay 1997)
Liver transplant recipients 2.5-4%(Galie 2001, Taura 1996, Castro 1996)
Incidence of PoPH
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Anemia can also increase cardiac output
baseline after 6 months
6MWT (m) 452 536
PA (mmHg)PVR (W)CI (L/min/m2)
77/31/m466.72.9
67/36/m493.95.5
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Anemia can also increase cardiac output
baseline after 6 months
6MWT (m) 452 536
PA (mmHg)PVR (W)CI (L/min/m2)
77/31/m466.72.9
67/36/m493.95.5Hb (g/dl) 13 11.5
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β-blocker cessation in PoPH
Provencher et al. Gastroenterology 2006
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Child-Pugh score
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RHC – hepatic veins
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RHC – hepatic veins
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RHC – hepatic veins
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44% had >20% difference between thermodilution and Fick
Using PVR >3 Wood units as a diagnostic criteria for PAH, 27 patients (13±2%) would have inconsistency in PAH diagnosis between TD and Fick
n=213 RHCs, 79 (40%) of whom had PAH
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PAH determinants of prognosis
ESC guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2009
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mPAP CI PCWP PVR TPG
Hyperdynamic < 35 NL NL
Volume overload < 35 NL NL <10
PoPH > 25 NL NL >10
Hemodynamics in portal hypertension
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REVEAL 2-year survival patterns for POPH and IPAH categorized by previous versus newly diagnosed (Dx) at the time of entry into the registry
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Current POPH screening evaluation and treatment algorithm used at the Mayo Clinic
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Cardiologist swimming in attractive waters of gastroenterology and respiratory medicine
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