PULMONARY ENDARTERECTOMY:
    THE PAVIA EXPERIENCE

                             Andrea M D’Armini, MD, FCCP
             ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                      INTRODUCTION


• Chronic thromboembolic pulmonary hy...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   INTRODUCTION
                              PEA vs. LTx
...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                                 EPIDEMIOLOGY
• Epidemiologic data: in Ita...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                CURRENT SITUATION


• CTEPH is still under-diagnosed and n...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

               NATURAL HISTORY

 • Pulmonary embolism (symptomatic / asymp...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

           GENERAL CONDITIONS

• Low cardiac output with dyspnea, cough, c...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

       COAGULATIVE DISORDERS
                           OF LAST 185 PEAs

...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

        IMMUNOLOGIC DISORDERS
                                OF LAST 185 ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

             GENETIC MUTATIONS
                           OF LAST 185 PEAs...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

     INDICATIONS FOR SURGERY

• The indications for the surgical treatment...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                             CLINIC

 • Patients must be in NYHA functiona...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   HEMODYNAMIC


• Pulmonary hypertension (mPAP > 25 mmHg)...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                          ANATOMY


• The surgical treatment depends on th...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

              PROXIMAL LESIONS




UNIVERSITY OF PAVIA SCHOOL OF MEDICINE ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

 M.B. – 62 yrs M – Jul 2001 – PEA #64

                                   ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   DISTAL LESIONS




UNIVERSITY OF PAVIA SCHOOL OF MEDICI...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

            S.S. – 31 yrs M – Sep 2002

                                  ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                    OUR PROGRAM


                  • National referral pr...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                     PATIENTS’ REFERRAL
                                  ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                                                PATIENTS’ AMOUNT

        ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   PAVIA CTEPH PROGRAM
                 January, 1st - Dec...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                    PAVIA CTEPH PROGRAM
                  January, 1st - D...
CHEST STUDIES: THE PAVIA EXPERIENCE

        MAIN WORLD PEA CENTERS
                                Cambridge, UK
        ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                 PEA POPULATION
                              OF 266 PEAs
...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

RIGHT HEART CATHETERIZATION
                              OF 266 PEAs



 ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

            ECHOCARDIOGRAPHY




UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

CARDIAC MAGNETIC RESONANCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

         ARTERIAL BLOOD GASES
                              OF 266 PEAs


...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

           MODIFIED BRUCE TEST
                              OF 266 PEAs

...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

CARDIOPULMONARY EXERCISE TESTING
                              OF 157 PEAs...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

CARDIOPULMONARY EXERCISE TESTING
                              OF 157 PEAs...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

PULMONARY ENDARTERECTOMY




UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

 TYPICAL SURGICAL SPECIMENS




 E.L. – 38 yrs M – Dec 1999 – PEA #42
 mPA...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

JAMIESON TYPE I vs. TYPE II vs. TYPE III




L.M.E.L. - 65 yrs M - Oct 200...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                    JAMIESON TYPE III




         B.A. - 43 yrs F - May 2...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       JAMIESON TYPE III




                             ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

           OUT OF PROPORTION PH ?




                                    ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                      JAMIESON TYPE III




                              ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

           OUT OF PROPORTION PH ?




                                    ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       JAMIESON TYPE III




                             ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

CUMULATIVE PROPORTION SURVIVING
                                          ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

CUMULATIVE PROPORTION SURVIVING
                                          ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                                           FOLLOW-UP


• Very few data are...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                 FOLLOW-UP TIMING


• All pts underwent follow-up evaluati...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   FOLLOW-UP DATA

• Eleven of 240 pts (4.6%) refused to p...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                   NYHA FUNCTIONAL CLASS
                                N...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

mean PULMONARY ARTERY PRESSURE
                   mean Pulmonary Arterial ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

PULMONARY VASCULAR RESISTANCES
                             Pulmonary Vasc...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

            ECHOCARDIOGRAPHY
                                 Before




U...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

            ECHOCARDOGRAPHY
                       First control – POD #9
...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

            ECHOCARDIOGRAPHY
                         Three-month control
...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

 CARDIAC MAGNETIC RESONANCE
         Before                               ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

 CARDIAC MAGNETIC RESONANCE
 First control – POD #6                       ...
PULMONARY ENDARTERECTOMY: REVERSE RIGHT VENTRICULAR REMODELING

   REVERSE RIGHT VENTRICULAR
          REMODELING




UNIV...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

BRAIN-TYPE NATRIURETIC PEPTIDE
              BNP TIME COURSE AFTER PEA
   ...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

ARTERIAL OXYGEN PARTIAL PRESSURE
                    Arterial Oxygen Parti...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                  MODIFIED BRUCE TEST

                             Modifi...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                           RESULTS
• In expert Centers mortality ranges be...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                              RESULTS
• The majority of pts experienced dr...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICIN...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE

  • April 1994 – October 2008

  • 204 P...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICIN...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICIN...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICIN...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

                       REFERENCE




UNIVERSITY OF PAVIA SCHOOL OF MEDICIN...
PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

        PATIENTS’ MANAGEMENT

  • Accurate NIRS monitoring during circulat...
RESULTS OF PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

PAVIA PULMONARY ENDARTERECTOMY GROUP
    •   Cardiac Surgery   ...
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Morsolini Marco Torino 13° Convegno Patologia Immune E Malattie Orfane 21 23 Gennaio 2010

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Morsolini Marco Torino 13° Convegno Patologia Immune E Malattie Orfane 21 23 Gennaio 2010

  1. 1. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE Andrea M D’Armini, MD, FCCP Marco Morsolini, MD, PhD Division of Cardiac Surgery University of Pavia School of Medicine St. Matteo Hospital Pavia - Italy UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  2. 2. 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 • This life-saving conservative surgery is called pulmonary endarterectomy (PEA) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  3. 3. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE INTRODUCTION PEA vs. LTx • Elective surgery, non donor-dependent • No “transplant window” to be considered • Age is not a contraindication • Lower post-operative complications – early (acute graft failure, acute rejection, infections) – late (BOS, neoplasms, infections) • Outcome – post-operative long term survival – quality of life (back to normal) – steady functional improvement UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  4. 4. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  5. 5. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE 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 6000 PEA have been performed worldwide so far with ≈ 40 % of all cases carried out by the San Diego Group UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  6. 6. 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) • Right ventricle hypertrophy with progressive right heart deterioration → right failure • Left ventricle compression with left heart functional impairment UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  7. 7. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  8. 8. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE COAGULATIVE DISORDERS OF LAST 185 PEAs 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  9. 9. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE IMMUNOLOGIC DISORDERS OF LAST 185 PEAs DISORDER % PTS MEAN ± SD RANGE Anti-Nuclear Antibodies (ANA) 23.4 % – – Lupus Anticoagulans (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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  10. 10. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE GENETIC MUTATIONS OF LAST 185 PEAs MUTATION % PTS C677T MTHFR (HOMOCYSTEINEMIA) HETEROZYGOSIS 50.8 % HOMOZYGOSIS 19.4 % TOTAL 70.2 % A1298C MTHFR (HOMOCYSTEINEMIA) HETEROZYGOSIS 44.4 % HOMOZYGOSIS 9.7 % TOTAL 54.1 % G20210A PROTHROMBIN (FACTOR II) 8.1 % G1691A FACTOR V (FACTOR V LEIDEN) 5.6 % UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  11. 11. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE INDICATIONS FOR SURGERY • 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 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  12. 12. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CLINIC • Patients must be in NYHA functional class III or IV • Full anticoagulation for at least 3 months • Some Authors (we too) recently have performed PEA even in NYHA class II patients, given the natural history of the disease UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  13. 13. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE HEMODYNAMIC • Pulmonary hypertension (mPAP > 25 mmHg) • Causing low cardiac output • Resulting in calculated pulmonary vascular resistances (PVR) > 300 dyne*sec*cm-5 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  14. 14. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ANATOMY • The surgical treatment depends on the localization of the lesions in the pulmonary arterial branches • Lesions can be classified as PROXIMAL DISTAL UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  15. 15. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PROXIMAL LESIONS UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  16. 16. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE M.B. – 62 yrs M – Jul 2001 – PEA #64 Perfusion and ventilation scan Pulmonary angiogram Hemodynamic mPAP 67 CI 1.6 PVR 1766 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  17. 17. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE DISTAL LESIONS UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  18. 18. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE S.S. – 31 yrs M – Sep 2002 Perfusion and ventilation scan Pulmonary angiogram Hemodynamic mPAP 50 CI 1.8 PVR 1120 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  19. 19. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE OUR PROGRAM • National referral program • Begin: April 1994 • To date: 266 PEAs performed UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  20. 20. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PATIENTS’ REFERRAL OF 266 PEAs 10 2 3 79 12 Pavia 40 12 14 Pts coming from outside Italy - Greece 1 19 2 - Uganda 1 6 4 16 1 11 10 6 1 ≤ 10 pts 11 – 20 pts 5 ≥ 21 pts 11 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  21. 21. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PATIENTS’ AMOUNT 54 PEAs in 1 yr • Apr ‘94 → Jan ‘10 60 • 266 PEAs (5 redo: 50 26, 40, 56, 86 and 174 months after the 40 first PEA) • In the majority of Patients 30 pts (250/266) an ICF 54 PEAs in 7 yrs was placed before 20 PEA • Lifelong 10 anticoagulation therapy was 0 prescribed 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  22. 22. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PAVIA CTEPH PROGRAM January, 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%) • PROXIMAL LESIONS (25 pts) • RECENT EMBOLIZATION (3 pts) - 22 PEAs - 2 medical therapy - 2 pts refused - 1 surgical embolectomy - 1 pt died on evaluation • TUMORS (5 pts) - 3 pulmonary angiosarcoma OPERABILITY RATE 74 % - 1 adenocarcinoma with pulmonary artery thrombosis - 1 intestinal tumor with liver metastases • DISTAL LESIONS (7 pts) • MISCELLANEOUS (12 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  23. 23. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PAVIA CTEPH PROGRAM January, 1st - December, 31st 2009 → 121 pts NEW EVALUATIONS (78 pts) PEAs FOLLOW-UP (43 pts) CONFIRMED (70 pts - 90%) OTHER DIAGNOSIS (8 pts - 10%) • MINIMAL CTE LESIONS WITHOUT PH (4 pts) • PROXIMAL LESIONS (62 pts) - 4 medical therapy - 54 PEAs • RECENT EMBOLIZATION (4 pts) - 1 pt waiting for PEA - 3 medical therapy - 4 pts refused PEA - 1 surgical embolectomy - 2 pts with “too old” lesions (pulmonary artery retraction) - 1 pt general condition too compromised OPERABILITY RATE 89 % • DISTAL LESIONS (8 pts) - 8 medical therapy: 5 too old for DLTx 3 too early for DLTx UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  24. 24. CHEST STUDIES: THE PAVIA EXPERIENCE MAIN WORLD PEA CENTERS Cambridge, UK ≈80 PEAs / year NATIONAL REFERRAL PROGRAM BY LAW Bad Nauheim, Germany ≈60 PEAs / year MORE THAN ONE PROGRAM Pavia, Italy ≈50 PEAs / year MORE THAN ONE PROGRAM San Diego, California, USA ≈120 PEAs / year NATIONAL REFERRAL PROGRAM FOR EXCELLENCE Paris, France ≈100 PEAs / year NATIONAL REFERRAL PROGRAM FOR EXCELLENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  25. 25. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PEA POPULATION OF 266 PEAs Age 56 ± 16 (11 − 84) years Gender 134 M – 132 F NYHA class 15 II – 122 III – 129 IV Length III / IV 19 ± 23 months Urgent / Emergent 64 / 266 Oxygen therapy 131 / 266 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  26. 26. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE RIGHT HEART CATHETERIZATION OF 266 PEAs Mean ± SD Range mPAP 47 ± 13 17 − 88 mmHg CI 1.9 ± 0.6 1.1 − 4.1 l/min/m2 PVR 1149 ± 535 191 − 3938 dynes*sec*cm-5 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  27. 27. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ECHOCARDIOGRAPHY UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  28. 28. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CARDIAC MAGNETIC RESONANCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  29. 29. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ARTERIAL BLOOD GASES OF 266 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  30. 30. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE MODIFIED BRUCE TEST OF 266 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  31. 31. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CARDIOPULMONARY EXERCISE TESTING OF 157 PEAs 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% UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  32. 32. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CARDIOPULMONARY EXERCISE TESTING OF 157 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 - ST. MATTEO HOSPITAL - PAVIA - ITALY
  33. 33. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PULMONARY ENDARTERECTOMY UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  34. 34. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE TYPICAL SURGICAL SPECIMENS E.L. – 38 yrs M – Dec 1999 – PEA #42 mPAP 43 → 20 (-53%) CO 3.3 → 6.9 (+109%) PVR 994 → 220 (-78%) P.A. – 66 yrs M – Jun 2001 – PEA #60 mPAP 50 → 25 (-50%) CO 2.6 → 4.4 (+69%) PVR 1385 → 364 (-74%) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  35. 35. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE JAMIESON TYPE I vs. TYPE II vs. TYPE III L.M.E.L. - 65 yrs M - Oct 2004 - PEA #119 mPAP 39 → 19 (-51%) CO 4.4 → 5.4 (+23%) PVR 665 → 222 (-66%) G.A.C. - 52 yrs F - Jul 2003 - PEA #96 mPAP 48 → 27 (-44%) CO 2.1 → 4.2 (+100%) PVR 1638 → 381 (-77%) S.F. - 48 yrs F - Mar 2009 - PEA #221 mPAP 44 → 29 (-34%) CO 2.9 → 3.5 (+21%) PVR 1131 → 549 (-51%) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  36. 36. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE JAMIESON TYPE III B.A. - 43 yrs F - May 2009 - PEA #233 mPAP 49 → 19 (-61%) CO 3.3 → 5.0 (+52%) RVEF 16 → 35 (+119%) PVR 1067 → 224 (-79%) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  37. 37. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE JAMIESON TYPE III Pre-operative Pulmonary Angiogram F.C. - 33 yrs F - Apr 2009 - PEA #225 mPAP 52 → 20 (-62%) CO 4.6 → 4.7 (+2%) RVEF 32 → 41 (+28%) PVR 870 → 255 (-71%) Pre-operative 64-HRCT UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  38. 38. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE OUT OF PROPORTION PH ? Pre-operative Pulmonary Angiogram B.R.A. - 72 yrs F mPAP 44 CO 2.9 RVEF 28 PVR 1159 Pre-operative 64-HRCT UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  39. 39. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE JAMIESON TYPE III Pre-operative Pulmonary Angiogram B.R.A. - 72 yrs F - Mar 2009 - PEA #222 mPAP 44 → 33 (-25%) CO 2.9 → 4.9 (+69%) RVEF 28 → 34 (+21%) PVR 1159 → 457 (-61%) Pre-operative 64-HRCT UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  40. 40. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE OUT OF PROPORTION PH ? Pre-operative Pulmonary Angiogram G.G. - 62 yrs F mPAP 51 CO 2.6 RVEF 19 PVR 1415 Pre-operative 64-HRCT UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  41. 41. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE JAMIESON TYPE III Pre-operative Pulmonary Angiogram G.G. - 62 yrs F - Sep 2009 - PEA #240 mPAP 51 → 27 (-47%) CO 2.6 → 4.0 (+54%) RVEF 19 → 24 (+26%) PVR 1415 → 460 (-68%) Pre-operative 64-HRCT UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  42. 42. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CUMULATIVE PROPORTION SURVIVING OF 266 PEAs 100% 187 144 125 108 91 71 54 42 33 30 22 14 7 3 2 90% 89.2±1.9 80% 87.1±2.2 86.5±2.2 85.6±2.4 84.5±2.6 70% 83.1±2.9 81.6±3.2 60% 79.2±3.9 79.2±3.9 Percentage 50% 40% Operative mortality 30% Global 24/266 (9.0%) NYHA II 0/15 (0.0%) NYHA III 5/122 (4.1%) 20% NYHA IV 19/129 (14.7%) Jan 08 - Jan 10 5/92 (5.4%) 10% 0% 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 Months after PEA UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  43. 43. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CUMULATIVE PROPORTION SURVIVING SURGERY vs. MEDICAL THERAPY 1.0 133 113 93 54 34 14 0.9 0.8 86 .8±2.6 0.7 84.7±2.8 83.8±2.9 83.8±2.9 83.8±2.9 83.8±2.9 0.6 Percentage 0.5 0.4 0.3 0.2 0.1 0.0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Months after PEA D’Armini A.M. Ital Heart J 2005;6(10):861-8. Riedel M. Chest 1982;81(2):151-8. UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  44. 44. 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 D’Armini AM, Zanotti G, Ghio S, Magrini G, Pozzi M, Scelsi L, Meloni G, Klersy C, Viganò M. Reverse right ventricular remodeling after pulmonary endarterectomy. J Thorac Cardiovasc Surg 2007; 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 Med 2008;178(4):419-24 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  45. 45. 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 procedure) – 3th month – yearly for 5 years – 7th, 10th and 15th year (10 controls) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  46. 46. 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 class on a phone-call basis • All the other pts (95.4%) have actively participated to the FUP study UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  47. 47. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE NYHA FUNCTIONAL CLASS NYHA Functional Class 100 90 80 70 % patients 60 I-II 50 III-IV 40 30 20 10 0 Pre-op Pre-op 3 3m mesi 1y 1 anno 3y 3 anni 5 5y anni 7 7y anni 10y 10 anni Follow-up p < 0.01 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  48. 48. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE mean PULMONARY ARTERY PRESSURE mean Pulmonary Arterial Pressure 60 50 40 mmHg 30 20 10 0 Pre-op Pre-op Dimiss disch 3 mesi 3m 1 anno 1y 3 anni 3y 5 anni 5y 7 anni 7y 10 10y anni Follow-up p < 0.01 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  49. 49. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE PULMONARY VASCULAR RESISTANCES Pulmonary Vascular Resistances 1200 1000 dyne*sec*cm-5 800 600 400 200 0 Pre-op Pre-op Dimiss disch 3 mesi 3m 1 anno 1y 3 anni 3y 5 anni 5y 7 anni 7y 10 10y anni Follow-up p < 0.01 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  50. 50. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ECHOCARDIOGRAPHY Before UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  51. 51. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ECHOCARDOGRAPHY First control – POD #9 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  52. 52. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ECHOCARDIOGRAPHY Three-month control UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  53. 53. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CARDIAC MAGNETIC RESONANCE Before First control – POD #6 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  54. 54. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE CARDIAC MAGNETIC RESONANCE First control – POD #6 Four-year control UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  55. 55. PULMONARY ENDARTERECTOMY: REVERSE RIGHT VENTRICULAR REMODELING REVERSE RIGHT VENTRICULAR REMODELING UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  56. 56. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE BRAIN-TYPE NATRIURETIC PEPTIDE BNP TIME COURSE AFTER PEA SERUMplasmatici di BNP Livelli BNP LEVELS 450.0 400.0 350.0 300.0 250.0 p g /m l 200.0 150.0 100.0 50.0 0.0 PRE-OP PRE-OP DISCHARGE DIMISSIONE 3 MONTHS 3 MESI 1 YEAR 1 ANNO 2 YEARS 2 ANNI UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  57. 57. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE ARTERIAL OXYGEN PARTIAL PRESSURE Arterial Oxygen Partial Pressure 100 90 80 70 mmHg 60 50 40 30 20 10 0 Pre-op Pre-op 3 3m mesi 1 anno 1y 3 3y anni 5 anni 5y 7 anni 7y 10 anni 10y Follow-up p < 0.01 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  58. 58. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE MODIFIED BRUCE TEST Modified Bruce Test 1000 900 800 700 meters 600 500 400 300 200 100 0 Pre-op Pre-op 3 3m mesi 1 anno 1y 3 anni 3y 5 anni 5y 7 7y anni 1010y anni Follow-up p < 0.01 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  59. 59. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE RESULTS • In expert Centers mortality ranges between 5% and 12% and technical failure is below 8% • Early hemodynamic results are known to be excellent in case of successful operation UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  60. 60. 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) • The functional results also show a progressive good recovery over a longer time (about years) UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  61. 61. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  62. 62. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE • April 1994 – October 2008 • 204 PEAs performed • 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 UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  63. 63. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  64. 64. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  65. 65. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  66. 66. PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE REFERENCE UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  67. 67. 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 • Inferior vena cava filter positioning • Accurate post-operative follow-up UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY
  68. 68. RESULTS OF PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE 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 • Critical 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 • 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 • Biostatistics C Klersy UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - ST. MATTEO HOSPITAL - PAVIA - ITALY

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