ipertensione polmonare postembolica-cteph
DESCRIPTION
IPERTENSIONE POLMONARE CRONICA TROMBOEMBOLICA, CTEPHTRANSCRIPT
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Andrea M D’Armini, MD, FCCP
CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSIONFROM TRANSPLANT TO CONSERVATIVE SURGERY
Cardiac SurgeryUniversity of Pavia School of Medicine
Foundation I.R.C.C.S. “San Matteo” HospitalPavia, Italy
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
BACKGROUND
Chronic Thromboembolic Pulmonary Hypertension
Acute Pulmonary Embolism
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Chronic thromboembolic pulmonary hypertension (CTEPH) represents a sequel of non-resolved venous thromboembolism with fatal natural history due to chronic right ventricular failure
• Progress in surgical treatment over the past decade has considerably improved the outcome of CTEPH patients
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
BACKGROUND
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
INTRODUCTION
• CTEPH represents the only type of pulmonary hypertension surgically treatable, in the majority of cases, without transplant
• This life-saving conservative surgery is called pulmonary endarterectomy (PEA)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Vascular lung diseases suitable for transplantation are:
• Idiopathic Pulmonary Hypertension
• Eisenmenger’s Syndrome
• CTEPH
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
VASCULAR LUNG DISEASES
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Eisenmenger’s Syndrome
• Idiophatic Pulmonary Hypertension
1990 2011
Optimal Medical Therapy
BEFORE
HL/L Transplantation
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
VASCULAR LUNG DISEASES
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• 1007 HEART TRANSPLANTS
• 309 LUNG TRANSPLANTS
• 39 HEART-LUNG TRANSPLANTS
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
1355 INTRATHORACIC TRANSPLANTS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
348 LUNG AND HEART-LUNG TRANSPLANTS• 79 VASCULAR LUNG DISEASES
• 269 PARENCHYMAL LUNG DISEASES
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
U. G. PRE DLTx U. G. 1° POST DLTx
DLTx for FAMILIAL PULMONARY HYPERTENSION
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
DLTx for FAMILIAL PULMONARY HYPERTENSION
RIGHT HEART CATHETERIZATION
PRE-DLTx 1° POST-DLTx
Right Atrium 13 9
Right Ventricle 118/0 25/0
Pulmonary Arterial Pressure 118/82/60 38/25/16 (-70%)
Systemic Arterial Pressure 96/76/61 113/73/53
Pulmonary Capillary Wedge Pressure 5 10
Cardiac Output 2.9 6.2 (+114%)
Cardiac index 1.6 4.0
Pulmonary Vascular Resistance 2134 155 (-91%)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
HLTx for EISENMENGER’S SYNDROME
M. P. PRE HLTx M. P. 1° POST HLTx
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
HLTx for EISENMENGER’S SYNDROME
Systolic Pulmonary Arterial Pressure 105 mmHg
Right Ventricular End-Diastolic Diameter 110 mm
Inferior Vena Cava 34 mm
PRE-OPERATIVE ECHOCARDIOGRAPHY
Right Atrium 6 mmHg
Right Ventricle 23/0 mmHg
Pulmonary Arterial Pressure 23/11/6 mmHg
Pulmonary Capillary Wedge Pressure 6 mmHg
Cardiac Output 7.1 L/min
Cardiac Index 4.3 L/min/m2
Pulmonary Vascular Resistance 45 dyne*sec*cm-5
POST-OPERATIVE RIGHT HEART CATHETERIZATION
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
THORACIC TRANSPLANTATION1355 TRANSPLANTS (17/11/1985 – 19/05/2011)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
1990 2011
From Transplant
to Conservative Surgery (PEA)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
SURGICAL TREATMENT OF CTEPHPAVIA EXPERIENCE - 356 PEAs
• CTEPH(NO SPECIFIC DRUGS ARE CURRENTLY APPROVED FOR CTEPH)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
EPIDEMIOLOGY
• Epidemiologic data: in Italy ≈ 65.000 cases / year of acute symptomatic pulmonary embolism (PE)
• Prevalence of CTEPH in pts surviving an acute PE (≈ 80 %) is calculated between 0.5% – 3.8%
→ up to 2.000 new cases / year
• Considering asymptomatic pulmonary embolism and misdiagnosed pulmonary embolism, the true incidence of CTEPH may be even greater
• Jamieson SW, Kapelanski DP. Pulmonary endarterectomy. Curr Probl Surg 2000; 37:165-252
• Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2001; 345:1465-72
• Pengo V, Lensing AV, Prins MH, Marchiori A, Davidson BL, Tiozzo F et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350:2257-64
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CURRENT SITUATION
• CTEPH is still under-diagnosed and nowadays only few physicians are aware of the surgical procedure called PEA
• For all these reasons about 9000 PEA have been performed worldwide so far with ≈ 30 % of all cases carried out by the San Diego Group
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
NATURAL HISTORY
• Pulmonary embolism (symptomatic / asymptomatic)
• “Honeymoon” period: months / years
• Hypertensive remodeling of the patent pulmonary vascular bed (Eisenmenger-like)
• Right ventricle hypertrophy with progressive right heart deterioration right failure
• Left ventricle compression with left heart functional impairment
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
GENERAL CONDITIONS
• Low cardiac output with dyspnea, cough, cyanosis, hepatomegaly, ascites, lower limb edema, syncope, hemoptysis and interscapular olosystolic murmur
• Hypoxemia with exercise, sometimes at rest also
• Frequent positive anamnesis for deep venous thrombosis and / or coagulative and immunologic disorders
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
COAGULATIVE DISORDERS
DISORDER % PTS MEAN ± SD RANGE
HYPERHOMOCYSTEINEMIA (μmol/L) 72.6 % 21.7 ± 8.3 14.1 – 63.2
EXCESS FACTOR VIII ANTIGEN (%) 78.2 % 206.7 ± 33.9 161.1 – 392.9
EXCESS FACTOR VIII RISTOCETIN (%) 47.6 % 182.1 ± 46.6 150.0 – 334.0
EXCESS FACTOR VIII (%) 27.4 % 179.3 ± 25.8 153.4 – 220.0
PAI EXCESS (U/ml) 53.2 % 5.1 ± 1.2 3.6 – 7.9
FACTOR V LEIDEN 15.3 % 1.34 ± 0.55 0.50 – 1.99
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
IMMUNOLOGIC DISORDERS
DISORDER % PTS MEAN ± SD RANGE
Anti-Nuclear Antibodies (ANA) 23.4 % – –
Lupus Anticoagulant (LAC) 19.4 % – –
Anti-Cardiolipin Antibodies (ACA) IgG 20.2 % 56.3 ± 40.3 10.3 – 121.0
Anti-Cardiolipin Antibodies (ACA) IgM 13.7 % 30.8 ± 30.5 7.3 – 101.0
Anti-Phospholipid Antibodies (APA) IgG 14.5 % 63.2 ± 36.5 8.4 – 121.0
Anti-Phospholipid Antibodies (APA) IgM 12.9 % 28.0 ± 23.5 10.1 – 91.3
Positive Direct Coombs’ Test 8.9 % – –
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• A PERMANENT INFERIOR VENA CAVA FILTER was placed before PEA in the majority (333/356) of patients
• Lifelong oral anticoagulation was prescribed after PEA
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
MARKED THROMBOPHILIA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• The indications for the surgical treatment of these patients are based on
CLINIC
HEMODYNAMIC
• The indications for the type of surgery are based on
ANATOMY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
INDICATIONS FOR SURGERY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CLINIC
The clinical indication changes substantially
according to the different surgical treatment of CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Age < 60 yrs
• WHO III or IV
• Contraindications
• Tx “window”
• Age is not a contraindication
• Symptomatic PH (WHO II-III-IV)
• Absence of severe pulmonary parenchymal disease
• Elective surgery
Tx PEA
TRANSPLANT WINDOW
TOO LATETOO EARLY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CLINIC
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Pulmonary hypertension (mPAP 25 mmHg)
• Pulmonary wedge pressure < 15 mmHg
• Causing low cardiac output
• Resulting in calculated pulmonary vascular resistances (PVR) > 300 dyne*sec*cm-5
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
HEMODYNAMIC
PRECAPILLARY PULMONARY HYPERTENSION
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• The surgical treatment depends on the localization of the lesions in the pulmonary arterial branches
• Lesions can be classified asPROXIMAL
DISTAL
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ANATOMY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ANATOMYPROXIMAL LESIONS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
M.B. – 62 yrs M – Jul 2001 – PEA #64
Perfusion and ventilation scan
Pulmonary angiogram
Hemodynamic
mPAP 67CI 1.6PVR 1766
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ANATOMYDISTAL LESIONS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
S.S. – 31 yrs M – Sep 2002
Perfusion and ventilation scan
Pulmonary angiogram
Hemodynamic
mPAP 50CI 1.8PVR 1120
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Growing single surgeon’s experience due to learning curve
Which lesions have to be considered as inoperable?
• Different operability assessments from different Centers
(operability ranges from 60 – 90 % from unpublished data)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
OPERABILITY ASSESSMENT
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Concomitant severe parenchymal lung disease is the real absolute contraindication to PEA
Such patients are not suitable for PEA and must be listed for DLTx (if indicated)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CONTRAINDICATION TO PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
P.B. – 60 yrs M – Jun 2002
Perfusion and ventilation scintigraphy
Pulmonary angiography
CT scan
Hemodynamic
mPAP 28CI 1.9PVR 645
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• National referral program
• Begin: April 1994
• To date: 356 PEAs performed
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
OUR PROGRAM
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
55101
124
15
1916
28
7
47
205
18 153
6
14
Pts coming from outside Italy- Greece 1- Kosovo 1- Uganda 1
2
2
Pavia
≤ 10 pts
11 – 20 pts
≥ 21 pts
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PATIENTS’ REFERRALOF 356 PEAs
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
0
10
20
30
40
50
60
70
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Pat
ien
ts
65 PEAs in almost 8 yrs
65 PEAs in 1 yr
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
SURGICAL TREATMENT OF CTEPHPAVIA EXPERIENCE - 356 PEAs
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
MAIN WORLD PEA CENTERS
Paris, France≈100 PEAs / year
NATIONAL REFERRAL PROGRAM FOR EXCELLENCE
Cambridge, UK≈80 PEAs / year
NATIONAL REFERRAL PROGRAM BY LAW
Pavia, Italy≈60 PEAs / year
MORE THAN ONE PROGRAM
Bad Nauheim, Germany≈50 PEAs / year
MORE THAN ONE PROGRAM
San Diego, California, USA≈130 PEAs / year
NATIONAL REFERRAL PROGRAM FOR EXCELLENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
08-MAR-1991
First HLTx for CTEPH
11-APR-1994
First PEA
28-JUL-2003
First PEA in patient listed for DLTx
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
SURGICAL TREATMENT OF CTEPH
25-DEC-1995
First DLTx for CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Tx for CTEPH
0
1
2
3
4
5
6
7
8
1991-1995 1996-2000 2001-2005 2006-2010
MO
RE DIA
GN
OSI
SM
ORE DISTAL PEAs
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
TRANSPLANT FOR CTEPH 18 / 79
PATIENTS DIAGNOSED WITH CTEPH
0
10
20
30
40
50
60
70
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
PEAs PERFORMED
0
10
20
30
40
50
60
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
AMOUNT OF PATIENTSNEW EVALUATIONS
54
108
0
20
40
60
80
100
120
2004 2010
Pat
ien
ts
+ 100%
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
AMOUNT OF PATIENTSDIAGNOSTIC ACCURACY
34
82
20 260
10
20
30
40
50
60
70
80
90
2004 2010
Pat
ien
ts
IPCTE
Other
63%
76%
+ 13%
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
AMOUNT OF PATIENTSOPERABILITY RATE
25
73
9 90
10
20
30
40
50
60
70
80
2004 2010
Pat
ien
ts
Operable
Inoperable
74%
89%
+ 15%
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
AMOUNT OF PATIENTSPEAs PERFORMED
22
65
0
10
20
30
40
50
60
70
2004 2010
PE
As
+ 195 %
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PAVIA CTEPH PROGRAMJanuary, 1st - December, 31st 2004 130 pts
EVALUATION (54 pts) FOLLOW-UP (72 pts) DLTx (4 pts)
CONFIRMED (34 pts - 63%) OTHER DIAGNOSIS (20 pts - 37%)
• RECENT EMBOLIZATION (3 pts) - 2 medical therapy - 1 surgical embolectomy
• TUMORS (5 pts) - 3 pulmonary angiosarcoma - 1 adenocarcinoma with pulmonary artery thrombosis - 1 intestinal tumor with liver metastases
• MISCELLANEOUS (12 pts)
OPERABILITY RATE 74 %
• PROXIMAL LESIONS (25 pts) - 22 PEAs - 2 pts refused - 1 pt died on evaluation
• DISTAL LESIONS (7 pts) - 5 DLTx waiting-list - 2 medical therapy (too old for DLTx)
• ASSOCIATION WITH SEVERE EMPHYSEMA (2 pts) - 2 DLTx waiting-list
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PAVIA CTEPH PROGRAMJanuary, 1st – December, 31st 2010 231 pts
New Evaluations (108 pts) PEAs FUP (99 pts) Clinical Trials (23 pts) HLTx (1 pt)
CONFIRMED (82 pts - 76%) OTHER DIAGNOSIS (26 pts - 24%)
OPERABILITY RATE 89 %
• PROXIMAL LESIONS (73 pts) - 65 PEAs - 4 pts waiting for PEA - 3 pts refused PEA - 1 pt with severe co-morbidities
• DISTAL LESIONS (8 pts) - 8 medical therapy: 5 too old for DLTx 3 too early for DLTx
• RECENT EMBOLIZATION (6 pts) - 3 medical therapy - 3 surgical embolectomy
• MINIMAL CTE LESIONS WITHOUT PH (2 pts) - 2 medical therapy
• MISCELLANEOUS (15 pts)
• TUMOR (3 pts) - 3 pulmonary angiosarcoma
• ASSOCIATION WITH SEVERE EMPHYSEMA (1 pt) - 1 DLTx waiting-list
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PAVIA CTEPH PROGRAMJanuary, 1st – May, 19th 2011 122 pts
New Evaluations (50 pts) PEAs FUP (56 pts) Clinical Trials (15 pts) DL/HLTx (1 pt)
CONFIRMED (28 pts - 56%) OTHER DIAGNOSIS (22 pts - 44%)
OPERABILITY RATE 93 %
• PROXIMAL LESIONS (26 pts) - 28 PEAs (4 pts evaluated in 2010) - 2 pts waiting for PEA
• DISTAL LESIONS (2 pts) - 2 medical therapy: 1 too old for DLTx 1 too early for DLTx
• MISCELLANEOUS (21 pts)
• TUMOR (1 pt) - 1 pulmonary angiosarcoma
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PEA POPULATIONOF 356 PEAs
Age 56 16 (11 84) years
Gender 170 M – 182 F
NYHA class 31 II – 165 III – 156 IV
Length III / IV 19 23 months
Urgent / Emergent 74 / 352
Oxygen therapy 171 / 352
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ECHOCARDIOGRAPHY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CARDIAC MAGNETIC RESONANCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ARTERIAL BLOOD GASESOF 356 PEAs
Mean SD Range
Pa O2 65 10 43 97 mmHg
Pa CO2 31 7 24 43 mmHg
O2-sat 93 3 84 98 %
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
MODIFIED BRUCE TESTOF 356 PEAs
Steps Walking distance
No (Pa O2 < 60) 36.9% 103 ± 160 (0 – 852) meters
Step 0 - ½ 56.8%
Step 1 - 2 4.5%
Step 3 - 4 1.8%
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Peak exercise
No (ECG, advanced NYHA IV, other) 16.3%
Watts 25 12.0%
Watts >25 / 50 50.0%
Watts >50 / 75 15.2%
Watts >75 6.5%
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CARDIOPULMONARY EXERCISE TESTINGOF 200 PEAs
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CARDIOPULMONARY EXERCISE TESTINGOF 200 PEAs
Mean SD Range
Peak-DP 16037 4822 5600 30600 mmHg*FC
Peak-VO2 9.9 3.6 3.0 29.4 ml/min/kg
Peak-Exe 50 22 15 160 watt
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PULMONARY ENDARTERECTOMY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
E.L. – 38 yrs M – Dec 1999 – PEA #42mPAP 43 20 (-53%)CO 3.3 6.9 (+109%)PVR 994 220 (-78%)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
TYPICAL SURGICAL SPECIMENS
P.A. – 66 yrs M – Jun 2001 – PEA #60mPAP 50 25 (-50%)CO 2.6 4.4 (+69%)PVR 1385 364 (-74%)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
DISTAL LESIONSJAMIESON TYPE IIILEARNING CURVE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE I vs. TYPE II vs. TYPE III
L.M.E.L. - 65 yrs M - Oct 2004 - PEA #119mPAP 39 19 (-51%)CO 4.4 5.4 (+23%)PVR 665 222 (-66%)
G.A.C. - 52 yrs F - Jul 2003 - PEA #96mPAP 48 27 (-44%)CO 2.1 4.2 (+100%)PVR 1638 381 (-77%)
B.A. - 43 yrs F - May 2009 - PEA #233mPAP 49 19 (-61%)CO 3.3 5.0 (+52%)PVR 1067 224 (-79%)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
B.A. - 43 yrs F - May 2009 - PEA #233mPAP 49 19 (-61%)CO 3.3 5.0 (+52%)RVEF 16 35 (+119%)PVR 1067 224 (-79%)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative Pulmonary Angiogram
Pre-operative 64-HRCT
F.C. - 33 yrs F - Apr 2009 - PEA #225mPAP 52 20 (-62%)CO 4.6 4.7 (+2%)RVEF 32 41 (+28%)PVR 870 255 (-71%)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative Pulmonary Angiogram
Pre-operative 64-HRCT
B.R.A. - 72 yrs FmPAP 44CO 2.9RVEF 28PVR 1159
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
INOPERABILE CTEPH?
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative Pulmonary Angiogram
Pre-operative 64-HRCT
B.R.A. - 72 yrs F - Mar 2009 - PEA #222mPAP 44 33 (-25%)CO 2.9 4.9 (+69%)RVEF 28 34 (+21%)PVR 1159 457 (-61%)
B.R.A. - 72 yrs FmPAP 44CO 2.9RVEF 28PVR 1159
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON’S TYPE III DISEASE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative Pulmonary Angiogram
Pre-operative 64-HRCT
G.G. - 62 yrs FmPAP 51CO 2.6RVEF 19PVR 1415
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
INOPERABILE CTEPH?
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative Pulmonary Angiogram
Pre-operative 64-HRCT
G.G. - 62 yrs F - Sep 2009 - PEA #240mPAP 51 27 (-47%)CO 2.6 4.0 (+54%)RVEF 19 24 (+26%)PVR 1415 460 (-68%)
G.G. - 62 yrs FmPAP 51CO 2.6RVEF 19PVR 1415
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON’S TYPE III DISEASE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
From July 2003 to date, 27 PEAs were performed in patients with
– age < 60 years
– severe dyspnea (WHO III – IV)
– distal CTEPH (Jamieson type III)
…otherwise they would have been listed for transplantation
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
A peculiar case: a “seasoned veteran” in CTEPH
XX-XX-1949
ITALIANVARESE
HOUSE PAINTER
150 cm
48 KgSystemic arterial hypertension
Gastroesophageal reflux disease
P. F. #255
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
JULY 2005Admission to the Cardiology ward of a local hospital
• ECG: right ventricle overload
• Echocardiogram: dilation and hypokinesia of the right chambers
severe tricuspid regurgitation
severe pulmonary hypertension (sPAP 85 mmHg)
• Lung V/Q scan: bilateral mismatches with multiple perfusion defects
• HRCT scan: multiple bilateral segmental perfusion defects
• Venous echocolordoppler of lower limbs : negative
JUNE 2004Onset of mild dyspnea (WHO II)
JUNE 2005Worsening of dyspnea (WHO III)
CTEPH
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SEPTEMBER 2005Admission to our Division for operability assessment
• COMPLETE DIAGNOSTIC WORKUP: CTEPH CONFIRMED
• Right Heart Catheterization: RA 1 mmHg
RV 82 / 0 mmHg
PA 82 / 39 / 13 mmHg
PCWP 3 mmHg
CO 3.3 L/min
CI 2.2 L/min
RVEF 25 %
PVRP 873 dyn*s*cm-5
• OPERABILITY: INOPERABLE FOR EXCLUSIVELY DISTAL DISEASE
DOUBLE LUNG TRANSPLANT WAITING LIST
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
LUNG V/Q SCAN
VENTILATION PERFUSION
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ANGIOGRAM
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
HRCT SCAN
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
DECEMBER 2005Enrollment in the BENEFIT study
(bosentan vs. placebo in inoperable forms of CTEPH)
Enrollment
27-DEC-2005
End of study (16 weeks)
28-APR-2006
Open label extension
26-OCT-2006
RA 4 4 6 mmHg
RV 82/2 82/0 85/3 mmHg
PA 82/46/24 82/45/22 85/49/28 mmHg
PCWP 5 5 5 mmHg
CO 3.1 2.4 3.0 L/min
CI 2.1 1.6 2.0 L/min/m2
RVEF 34 11 12 %
PVR 1057 1343 1164 dyn*s*cm-5
Serum-BNP 360 324 151 pg/ml
WHO III III II
INOPERABILITY CONFIRMED BY THE INTERNATIONAL COMMITTEE
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
BENEFIT and BENEFIT-OPEN LABEL EXTENSIONClinical course
6mWT
270290
480456 462
442418
0
100
200
300
400
500
600
Dec-05 Apr-06 Oct-06 May-07 Oct-07 May-08 J an-09
Follow-up
me
ters
15-FEB-2008 Withdrawal from DLTx waiting list
WHO III WHO II
BENEFIT-Open LabelBENEFIT
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
BILATERAL PULMONARY ENDARTERECTOMY
Right: upper, middle and lower lobeLeft: upper lobe, lingula and lower lobe
Moderate hypothermia (23° C)
Intermittent circulatory arrests right side: 91 minleft side: 47 mintotal time: 138 min
OCTOBER 2009Worsening of dyspnea (back to WHO III)
NOVEMBER 2009Admission to our Division for therapy update
NEW OPERABILITY ASSESSMENT → NOW TECHNICALLY OPERABLE
(JUST ALIKE THE PREVIOUS FINDINGS)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
BILATERAL PEA – SURGICAL SPECIMEN
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Preoperative
27-NOV-2009
At discharge
15-DEC-2009
3 months FUP
26-FEB-2010
RA 7 3 3 mmHg
RV 120/0 53/0 35/0 mmHg
PA 120/65/36 53/22/8 35/19/12 mmHg
PCWP 5 5 5 mmHg
CO 3.5 3.9 4.2 L/min
CI 2.4 2.7 2.9 L/min/m2
RVEF 6 18 21 %
PVR 1371 308 267 dyn*s*cm-5
Serum-BNP 996 742 106 pg/ml
WHO III I I
– 81 %
BILATERAL PEAHemodynamic results
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
A peculiar case: a “seasoned veteran” in CTEPH
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
The “seasoned veteran”
DIAGNOSIS
TRANSPLANT WAITING LIST
SPECIFIC MEDICAL THERAPY PULMONARY
ENDARTERECTOMY(Gold Standard)
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
JAMIESON TYPE III
SPECIFIC PAH-DRUG DISCONTINUATION
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180
Months after PEA
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%P
erc
ent
age
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CUMULATIVE PROPORTION SURVIVINGOF 356 PEAs
Operative mortality Global 32/356 (9.0%) NYHA II 0/32 (0.0%) NYHA III 8/165 (4.8%) NYHA IV 24/159 (15.1%)
Jan 08 – May 11 13/182 (7.1%)
187 144 125 108 91 71 54 42 33 30 22 14 7 3 2
89.21.9 87.12.
2 86.52.2
85.62.4 84.52.
6 83.12.9 81.63.
2 79.23.9
79.23.9
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CUMULATIVE PROPORTION SURVIVING45 PTS ON WAITING LIST FOR TRANSPLANT IN CTEPH
SURVIVALWAITING LIST FOR TRANSPLANT IN CTEPH
0 365 730 1095 1460 1825 2190 2555 2920 3285 3650 4015 4380
Time (days)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cum
ulat
ive
Prop
ortio
n Su
rviv
al
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CUMULATIVE PROPORTION SURVIVING18 TRANSPLANTS IN CTEPH
SURVIVALTRANSPLANT IN CTEPH
0 365 730 1095 1460 1825 2190 2555 2920 3285 3650 4015 4380 4745 5110 5475
Time (days)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cum
ulat
ive
Prop
ortio
n Su
rviv
al
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
FOLLOW-UP
In literature few data are reported on mid- and long- term cardiopulmonary function, particularly on exertion, and on clinical outcomes after PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
FOLLOW-UP TIMING
• All pts underwent follow-up evaluation at:– discharge (at this interval NYHA class, lung function, and exercise
tolerance are excluded because pts are to close to the surgical procedure)
– 3th month
– yearly for 5 years
– 7th, 10th and 15th year (10 controls)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
NYHA FUNCTIONAL CLASS
NYHA Functional Class
0
10
20
30
40
50
60
70
80
90
100
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
% p
ati
ents
I -I I
I I I -IV
Pre-op 3m 1y 3y 5y 7y 10y
pp < 0.01 < 0.01
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
mean PULMONARY ARTERY PRESSURE
mean Pulmonary Arterial Pressure
0
10
20
30
40
50
60
Pre-op Dimiss 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
mm
Hg
pp < 0.01 < 0.01
Pre-op disch 3m 1y 3y 5y 7y 10y
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PULMONARY VASCULAR RESISTANCES
Pulmonary Vascular Resistances
0
200
400
600
800
1000
1200
Pre-op Dimiss 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
dyne*se
c*cm
-5
pp < 0.01 < 0.01
Pre-op disch 3m 1y 3y 5y 7y 10y
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ECHOCARDIOGRAPHYBefore PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ECHOCARDOGRAPHYFirst echo after PEA – POD #9
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ECHOCARDIOGRAPHY3-months FUP after PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CARDIAC MAGNETIC RESONANCEBefore PEA First CMR after PEA – POD #6
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CARDIAC MAGNETIC RESONANCE4-years FUP after PEAFirst CMR after PEA – POD #6
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
ARTERIAL OXYGEN PARTIAL PRESSURE
Arterial Oxygen Partial Pressure
0
10
20
30
40
50
60
70
80
90
100
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
mm
Hg
pp < 0.01 < 0.01
Pre-op 3m 1y 3y 5y 7y 10y
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
MODIFIED BRUCE TEST
Modified Bruce Test
0
100
200
300
400
500
600
700
800
900
1000
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
met
ers
pp < 0.01 < 0.01
Pre-op 3m 1y 3y 5y 7y 10y
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
RESULTS• The majority of pts experienced dramatic improvement in
pulmonary hemodynamics after PEA
• After PEA the decrease in pulmonary artery pressure is immediate (in O.R.) and associated with complete recovery of RV morphology (at discharge)
• The functional results also show a progressive good recovery over a longer time (about years)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
RESULTS
• About 10-15% of our pts showed no statistically significant differences compared to pre-op or a persistent PH after PEA
• About 5-10% of our pts showed a new increase in pulmonary pressure after PEA over time
• The reason could be a secondary small vessel arteriopathy (Eisenmenger-type syndrome) in the non-obstructed segments of the lungs already present at the time of PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
MEDICAL THERAPYINOPERABLE CTEPH OR
RECURRENT PH AFTER PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
OPERABILITY ASSESSMENT
Some patients can not undergo PEA, due to:
• Significant comorbilities (i.e.: severe parenchymal lung disease, malignacy)
• Pulmonary arteries retraction following long lasting total obstruction
• Exclusively distal lesions
CLINICAL TRIAL TARGET
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative V/Q scan
Pre-operative right pulmonary angiogram
Pre-operative RHCmPAP 50CI 1.4PVR 1241RVEF 9
Extensive obstruction of the right proximal PA branches; only sub-segmental lesions on the left PA
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PRE-OPERATIVE LONG LASTING DISEASE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• A right monolateral PEA was performed
• Impossible to wean off the patient from cardio-pulmonary by-pass due to right ventricle failure
• On ECMO for two days; the sternum was left open for two more days
• Mechanical ventilation 9 days ICU stay 14 days Hospital stay
21 days
First PO RHC controlmPAP 26 (-48%)CI 2.0 (+43%)PVR 410 (-67%)RVEF 25 (+178%)
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PRE-OPERATIVE LONG LASTING DISEASE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Pre-operative
• “Steel” phenomenon in the non dissected branches (left lung) present at first control (before discharge)
• Usually reversible since the third month FUP
• In this case only partially reversibleBefore discharge
3-month FUP 1-year FUP 2-year FUP
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PRE-OPERATIVE LONG LASTING DISEASE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Riedel M. Chest 1982;81(2):151-8.
• No CT-scan evidence of new thromboembolic material
• Very long pre-operative NYHA III-IV class period (65 months): probably severe and non-reversible small vessels disease
RHC data FUP: 2 years
mean Pulmonary Artery Pressure
0
10
20
30
40
50
60
Before PEA Discharge 3 months 1 year 2 years
Cardiac Index
0.0
0.5
1.0
1.5
2.0
2.5
Before PEA Discharge 3 months 1 year 2 years
Pulmonary Vascular Resistances
0
200
400
600
800
1000
1200
1400
Before PEA Discharge 3 months 1 year 2 years
Right Ventricle Ejection Fraction
0
5
10
15
20
25
30
35
Before PEA Discharge 3 months 1 year 2 years
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PRE-OPERATIVE LONG LASTING DISEASE
TYPICAL PATIENT WITH
RECURRENT PH AFTER PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PAVIA CTEPH PROGRAMJanuary, 1st - December, 31st 2009 142 pts
NEW EVALUATIONS (99 pts) PEAs FOLLOW-UP (43 pts)
CONFIRMED (70 pts - 70%) OTHER DIAGNOSIS (29 pts - 30%)
OPERABILITY RATE 89 %
• PROXIMAL LESIONS (62 pts) - 54 PEAs - 1 pt waiting for PEA - 4 pts refused PEA - 2 pts with “too old” lesions (pulmonary artery retraction) - 1 pt general condition too compromised
• DISTAL LESIONS (8 pts)
- 8 medical therapy: 5 too old for DLTx 3 too early for DLTx
• RECENT EMBOLIZATION (4 pts) - 3 medical therapy - 1 surgical embolectomy
• MINIMAL CTE LESIONS WITHOUT PH (4 pts) - 4 medical therapy
9 CHEST SCREENING
- 6 INOPERABLE CTEPH
- 3 PH AFTER PEA
• MISCELLANEOUS (21 pts)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
HIGHER ENROLLING CENTERS FEATURES
National referral program
Higher patients amount
Higher operability rate
ANYWAY
number of inoperable patients
won’t be affectedCLINICAL TRIAL TARGETS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
Higher operability rate
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
HIGHER ENROLLING CENTERS FEATURES
More Jamieson type III PEAs
CLINICAL TRIAL TARGETS
Higher PH recurrence after PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PH – MEDICAL THERAPHY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
No drugs are currently approved for CTEPH
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CTEPH – MEDICAL THERAPHY
Further clinical trials are needed
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
STUDY DESIGN
• Phase III, randomized vs. placebo (1:1)
• International multicentre (26 sites in 13 Countries)
• 157 pts (18 – 80 yrs)
• CTEPH - inoperable (exclusively distal lesions)- persistent or recurrent PH after PEA
• WHO functional class II – IV
• 6mWT distance < 450 m
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
*Analysis excluded patients judged operable by the Operability Evaluation Committee (n=11)
†Analysis excluded patients with missing baseline or post-baseline assessment(s) (n=9 for pulmonary vascular resistance [PVR] analysis; n=6 for 6-min walk distance [6MWD] analysis)
mPAP = mean pulmonary artery pressure mRAP = mean right atrial pressure
NT-proBNP = N-terminal pro-brain natriuretic peptide; PEA = pulmonary endarterectomy; TPR = total pulmonary resistance; WHO = World Health Organization.
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BENEFiT STUDY
Jaïs X, D’Armini AM, Jansa P et al. J Am Coll Cardiol 2008 Dec 16;52(25):2127-34
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CHEST STUDY
RATIONALERATIONALERIOCIGUAT Soluble guanylate-cyclase stimulatorRIOCIGUAT Soluble guanylate-cyclase stimulator
Chronic Thromboembolic Pulmonary Hypertension sGC-Stimulator Trial
riociguat
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CHEST STUDYChronic Thromboembolic Pulmonary Hypertension
sGC-Stimulator Trial
• Phase III, double-blind, randomized vs. Placebo (2:1)• International, multicenter (28 Countries)• N = 270 pts (18 – 75 yrs)• Inoperable CTEPH (peripheral localization) or recurrent
PH after PEA• PH pts WHO II-IV• 6 MWD > 150 m and < 450 m• PVR > 480 dyne*sec*cm-5
• mPAP > 25 mmHg riociguat
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CHEST STUDYHIGHER ENROLLING CENTERS FEATURES
• Lower screening failures rate in Centers where an expert surgeon is actively involved in the operability assessment
• National referral program with high patients amount
• Good quality of imaging and expertise of radiologists
• Active PEA Program with scheduled follow-up visits
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• Slow recruitment
– each Center should NOT participate in more than one clinical trial for CTEPH (rare disease)
• High screening failure rate
– careful evaluation before screening
• Furthermore, it’s becoming more and more difficult to see untreated CTEPH patients (eligible for clinical trials)
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CHEST STUDYOPEN QUESTIONS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
CHEST STUDIES: THE PAVIA EXPERIENCE
CHESTTOP 5 ENROLLING CENTERS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CONCLUSION
• Poor survival rate of untreated pts (10% 5-yrs survival if mPAP 50 mmHg), low mortality rate after PEA and good mid- and long- term results confirm PEA as the procedure of choice for operable CTEPH pts
• The improvement of functional capacity strictly depends on the hemodynamic changes after PEA
• When CTEPH is diagnosed, given the natural history of the disease, patients should be referred for surgery even when in NYHA functional class II
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
• CTEPH pts should be referred early to Centres experienced in both PEA and Tx, to offer the best treatment and to achieve the best results
• This strategy maximizes the use of scarce donor organs by offering, when feasible, a non-transplant option
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
CONCLUSION
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY
SURGICAL TREATMENT OF CTEPH: FROM TRANSPLANT TO CONSERVATIVE SURGERY
PAVIA PULMONARY ENDARTERECTOMY GROUP
• Cardiac Surgery M Viganò, AM D’Armini, G Silvaggio, S Nicolardi, M Morsolini, G Mattiucci
• Anestesiology M Maurelli, T Bianchi, R Veronesi, M Toscani, C Dezza,
E Milanesi, B Lusona, B Rossini• Critical Care A Braschi, V Emmi, G Rodi, G Sala Gallini
F Capra Marzani, M Zanierato, F Mojoli• Cardiology L Oltrona Visconti, S Ghio, A Raisaro, L Scelsi, C
Raineri• Respiratory Disease M Luisetti, I Cerveri, A Corsico• Radiology I R Dore• Radiology II F Zappoli Thyrion, P Quaretti, A Azzaretti, G
Rodolico• Nuclear Medicine C Aprile• Reumatology C Montecucco, R Caporali• Thromboembolism F Piovella, M Barone, C Beltrametti• Pathology E Arbustini, M Grasso• General Rehabilitation E Dalla Toffola, L Petrucci• Pulmonary Rehabilitation C Fracchia, G Callegari• Biostatistics C Klersy