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

Wednesday, March 4, 15

03/04/152

Received:Travel fees from ACTELIONResearch funding from United Therapeutics

Disclosures

03/04/153

!Female!DoB: 17/11/1968, 47y

03/04/154

!2008! Autoimmune hepatitis! Liver cirrhosis! Smoker, history of mild asthma

!2009! episode of acute PE, anticoagulation for 6

months

Background

03/04/155

!2010! Portal hypertension (splenomegaly,

thrombocytopenia, mild oesophageal varices)! Portal thrombosis

!Hepatology assessment! Child-Pugh class B cirrhosis ! MELD score 12

Background

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

03/04/157

• Azathioprine 2mg/kg• Propranolol 40 mg tid• LMWH

Medications

03/04/158

!2010:

! shortness of breath on exertion, fatigue! no syncope! no chest pain

Background

03/04/159

!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

03/04/1510

Pre Post

SpO2 (%) 96 81

HR (bpm) 55 105

Borg score 1 6

Total walked distance: 471mTotal walked distance: 471mTotal walked distance: 471m

03/04/1511

"No signs of significant LV systolic or diastolic dysfunction

"No RV dilatation

"RVSP = 39 mmHg

03/04/1512

Bubble echo

Cycle 0

Cycle 6

03/04/1512

Bubble echo

Cycle 0

Cycle 6

03/04/1512

Bubble echo

Cycle 0

Cycle 6

03/04/1513

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

03/04/1514

!1 liter of supplemental oxygen per minute at rest and 3 liters per minute (L/min) with exertion

Management - Supplemental oxygen

03/04/1515

!Improved gradually with oxygen therapy

!Patient was placed on the liver transplant list with a MELD exception for HPS

Clinical course

03/04/1516

" 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

03/04/1517

! Mild RV dilatation! TAPSE 2.3cm! RVSP 85mmHg! Mild pericardial effusion

03/04/1518

• 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

03/04/1519

!Child-Pugh class B!MELD score 15

Hepatology workup

03/04/1520

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

03/04/1521

Pulmonary angiogram

Negative for CTEPH

03/04/1521

Pulmonary angiogram

Negative for CTEPH

03/04/1521

Pulmonary angiogram

Negative for CTEPH

03/04/1522

ERS Task Force Pulmonary-Hepatic Vascular Disorders Scientific Committee Guidelines for PoPH candidates for OLT

Rodriguez-Roisin R et al. Eur Respir J 2004

03/04/1523

!Withdrawn from liver transplant list

!Start bosentan (upitrated to 125 mg BID) with close LFT monitoring.

!Discontinued propranolol (prim. prevention)

Therapy

03/04/1524

!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

03/04/1525

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

03/04/1526

1. targeted therapy with ERA2. b-blocker cessation3. both

Significant CI increase could be attributed to

03/04/1527

" 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

03/04/1528

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

03/04/1529

Treatment goals

03/04/1529

Treatment goals

03/04/1529

Treatment goals

03/04/1529

Treatment goals

03/04/1529

Treatment goals

03/04/1529

Treatment goals

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

03/04/1531

!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

03/04/1532

" 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

Αριστοτέλειο Πανεπιστήμιο ΘεσσαλονίκηςΑ΄ Καρδιολογική Κλινική ΑΧΕΠΑ Διακλινικό Ιατρείο Πνευμονικής Υπέρτασης

03/04/15

Thank you!!

Back up slides

03/04/1536

!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

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

03/04/1540

!PoPH patients are usually excluded from RCTs with PAH-specific therapies

RCTs on medical therapy

03/04/1541

1. Add a PDE-5 inhibitor2. Do nothing3. Repeat the RHC using the indirect Fick

method

How would you proceed with this patient?

03/04/1542

Hepatic venous pressure gradient

Ripoll et al, Gastroenterology 2007 Ripoll et al, Hepatology, 2005

HVPG >12 mmHg Severe portal hypertension

HVPG>10mmHg

HVPG<10mmHg

Targeted PAH therapy with ambrisentan

Cartin-Ceba et al. Chest 2011

n=17 patients with PoPH treated with ambrisenten monotherapy

03/04/1545

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

03/04/1546

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

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

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

β-blocker cessation in PoPH

Provencher et al. Gastroenterology 2006

Child-Pugh score

03/04/1550

RHC – hepatic veins

03/04/1550

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

03/04/1552

PAH determinants of prognosis

ESC guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2009

03/04/1553

mPAP CI PCWP PVR TPG

Hyperdynamic < 35 NL NL

Volume overload < 35 NL NL <10

PoPH > 25 NL NL >10

Hemodynamics in portal hypertension

03/04/1554

REVEAL 2-year survival patterns for POPH and IPAH categorized by previous versus newly diagnosed (Dx) at the time of entry into the registry

03/04/1555

Current POPH screening evaluation and treatment algorithm used at the Mayo Clinic

03/04/1557

Cardiologist swimming in attractive waters of gastroenterology and respiratory medicine

A rare case of porto-pulmonary hypertensionstatic.livemedia.gr/hcs2/documents/al15205_us41...TAPSE...

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