Andrea M D’Armini, MD, FCCP Marco Morsolini, MD, PhD PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY Division of Cardiac Surgery University of Pavia School of Medicine St. Matteo Hospital Pavia - Italy
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Andrea M D’Armini, MD, FCCPMarco Morsolini, MD, PhD
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
Division of Cardiac SurgeryUniversity of Pavia School of MedicineSt. Matteo HospitalPavia - Italy
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
INTRODUCTION
• Chronic thromboembolic pulmonary hypertension (CTEPH)represents the only type of pulmonary hypertension surgically treatable, in the majority of cases, without transplant
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• This life-saving conservative surgery is called pulmonary endarterectomy (PEA)
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
INTRODUCTION
• Elective surgery, non donor-dependent
• No “transplant window” to be considered
• Age is not a contraindication
• Lower post-operative complications
PEA vs. LTx
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med2001; 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 Med2004; 350:2257-64
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CURRENT SITUATION
• CTEPH is still under-diagnosedand nowadays only few physicians are aware of the surgical procedurecalled PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• For all these reasons about 6000 PEAhave been performed worldwide so far with ≈ 40 %of all cases carried out by the San Diego Group
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
NATURAL HISTORY
• Pulmonary embolism (symptomatic / asymptomatic)
• “Honeymoon” period: months / years
• Hypertensive remodeling of the patent pulmonary vascular bed (Eisenmenger-like)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
vascular bed (Eisenmenger-like)
• Right ventricle hypertrophy with progressive right heart deterioration → right failure
• Left ventricle compression with left heart functional impairment
Operative mortalityGlobal 24/266 (9.0%)NYHA II 0/15 (0.0%)NYHA III 5/122 (4.1%)NYHA IV 19/129 (14.7%)
Jan 08 - Jan 10 5/92 (5.4%)
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Per
cent
age
133
86 .8±2.6
84.7±2.8
83.8±2.9 83.8±2.9 83.8±2.9 83.8±2.9
113 93 54 34 14
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CUMULATIVE PROPORTION SURVIVINGSURGERY vs. MEDICAL THERAPY
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0 12 24 36 48 60 72 84 96 108 120 132 144 156
Months after PEA
0.0
0.1
0.2
0.3
Riedel M. Chest 1982;81(2):151-8.
D’Armini A.M. Ital Heart J 2005;6(10):861-8.
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
FOLLOW -UP
• Very few data are available in the literature on mid and long term cardiopulmonary function, particularly on exertion, and on clinical benefits after PEA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
D’Armini AM, Zanotti G, Ghio S, Magrini G, Pozzi M, Scelsi L, Meloni G, Klersy C, Viganò M. Reverse right ventricular remodelingafter pulmonary endarterectomy. J Thorac Cardiovasc Surg2007; 133:162-8
Corsico AG, D’Armini AM, Cerveri I, Klersy C, Ansaldo E, Niniano R, Gatto E, Monterosso C, Morsolini M, Nicolardi S, Tramontin C, Pozzi E, Viganò M. Long-term outcome after pulmonary endarterectomy. Am J Respir Crit Care Med2008;178(4):419-24
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
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
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
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)
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
FOLLOW -UP DATA
• Eleven of 240 pts (4.6%) refused to participate to the study since the beginning (2/4 pts referred from outside Italy) or at various intervals
• For these pts we obtained only data on survival and NYHA
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• For these pts we obtained only data on survival and NYHA class on a phone-call basis
• All the other pts (95.4%) have actively participated to the FUP study
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
NYHA FUNCTIONAL CLASS
NYHA Functional Class
60
70
80
90
100
% patients
I-II
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0
10
20
30
40
50
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
% patients
I-II
III-IV
Pre-op 3m 1y 3y 5y 7y 10y
pp < 0.01< 0.01
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
mean PULMONARY ARTERY PRESSURE
mean Pulmonary Arterial Pressure
40
50
60
mmHg
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0
10
20
30
Pre-op Dimiss 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
mmHg
pp < 0.01< 0.01
Pre-op disch 3m 1y 3y 5y 7y 10y
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PULMONARY VASCULAR RESISTANCES
Pulmonary Vascular Resistances
800
1000
1200
dyne*sec*cm-5
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0
200
400
600
Pre-op Dimiss 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
dyne*sec*cm-5
pp < 0.01< 0.01
Pre-op disch 3m 1y 3y 5y 7y 10y
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
ECHOCARDIOGRAPHYBefore
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
ECHOCARDOGRAPHYFirst control – POD #9
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
ECHOCARDIOGRAPHYThree-month control
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CARDIAC MAGNETIC RESONANCEBefore First control – POD #6
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
CARDIAC MAGNETIC RESONANCEFirst control – POD #6 Four-year control
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: REVERSE RIGHT VENTRICULAR REMODELING
REVERSE RIGHT VENTRICULAR REMODELING
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
BRAIN-TYPE NATRIURETIC PEPTIDEBNP TIME COURSE AFTER PEA
Livelli plasmatici di BNP
350.0
400.0
450.0
SERUM BNP LEVELS
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0.0
50.0
100.0
150.0
200.0
250.0
300.0
PRE-OP DIMISSIONE 3 MESI 1 ANNO 2 ANNI
pg/m
l
PRE-OP DISCHARGE 3 MONTHS 1 YEAR 2 YEARS
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
ARTERIAL OXYGEN PARTIAL PRESSURE
Arterial Oxygen Partial Pressure
60
70
80
90
100
mmHg
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0
10
20
30
40
50
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
mmHg
pp < 0.01< 0.01
Pre-op 3m 1y 3y 5y 7y 10y
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
MODIFIED BRUCE TEST
Modified Bruce Test
600
700
800
900
1000
meters
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
0
100
200
300
400
500
600
Pre-op 3 mesi 1 anno 3 anni 5 anni 7 anni 10 anni
Follow-up
meters
pp < 0.01< 0.01
Pre-op 3m 1y 3y 5y 7y 10y
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
RESULTS
• In expert Centers mortality ranges between 5% and 12% and technical failure is below 8%
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• Early hemodynamic results are known to be excellent in case of successful operation
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
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)
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
RV morphology (at discharge)
• The functional results also show a progressive good recovery over a longer time (about years)
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• April 1994 – October 2008
• 204 PEAs performed
• 184 patients received a complete pre-operative
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• 184 patients received a complete pre-operative screening for thrombofilia
• Group A (HAPT– high titre > 10 U/ml) 28 pts
• Group B (LAPT– low titre > 10 U/ml) 156 pts
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
REFERENCE
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE
PATIENTS’ MANAGEMENT
• Accurate NIRS monitoring during circulatory arrests
• Attention even to minor neurological dysfunctions
• Careful anticoagulation with higher target INR
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• Careful anticoagulation with higher target INR
• Inferior vena cava filter positioning
• Accurate post-operative follow-up
RESULTS OF PULMONARY ENDARTERECTOMY: THE PAVIA EXPE RIENCE
PAVIA PULMONARY ENDARTERECTOMY GROUP
• Cardiac Surgery M Viganò, AM D’Armini, C Monterosso, G Silvaggio,
S Nicolardi, M Morsolini, D Berwick, G Mattiucci
• Anestesiology M Maurelli, T Bianchi, R Veronesi, M Toscani
MA Villani, E Milanesi, B Lusona, M Gerletti
• Cri tical Care A Braschi, V Emmi, G Rodi, G Sala Gallini
F Capra Marzani, F Mojoli
• Cardiology L Oltrona Visconti, S Ghio, A Raisaro, L Scelsi, C Raineri
• Respiratory Disease E Pozzi, I Cerveri, A Corsico
UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
• 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 U Magrini, E Arbustini, M Grasso
• General Rehabilitation E Dalla Toffola, L Petrucci
• Pulmonary Rehabilitation C Fracchia, G Callegari