CTEPH, Surgical and Medical Therapy. CTEPH, Terapia Chirurgica e Medica

UNIVERSITY OF PAVIA SCHOOL OF MEDICINE - SAN MATTEO HOSPITAL - PAVIA - ITALY

Andrea M D’Armini, MD, FCCP

PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE “CTEPH”

Cardiac SurgeryUniversity of Pavia School of Medicine

Foundation I.R.C.C.S. “San Matteo” HospitalPavia, Italy


PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

BACKGROUND

Chronic Thromboembolic Pulmonary Hypertension

CTEPH

Acute Pulmonary Embolism


• 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


BACKGROUND



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)


Vascular lung diseases suitable for transplantation are:

• Idiopathic Pulmonary Hypertension

• Eisenmenger’s Syndrome

• CTEPH


VASCULAR LUNG DISEASES


• Eisenmenger’s Syndrome

• Idiophatic Pulmonary Hypertension

1990 2011

Optimal Medical Therapy

BEFORE

HL/L Transplantation


VASCULAR LUNG DISEASES


• 10089 HEART TRANSPLANTS

• 309 LUNG TRANSPLANTS

• 39 HEART-LUNG TRANSPLANTS


THORACIC TRANSPLANTATION1357 TRANSPLANTS (17/11/1985 – 09/06/2011)

1357 INTRATHORACIC TRANSPLANTS


348 LUNG AND HEART-LUNG TRANSPLANTS• 79 VASCULAR LUNG DISEASES

• 269 PARENCHYMAL LUNG DISEASES




U. G. PRE DLTx U. G. 1° POST DLTx

DLTx for FAMILIAL PULMONARY HYPERTENSION




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%)




HLTx for EISENMENGER’S SYNDROME

M. P. PRE HLTx M. P. 1° POST HLTx




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




1990 2011

From Transplant

to Conservative Surgery (PEA)


SURGICAL TREATMENT OF CTEPHPAVIA EXPERIENCE - 357 PEAs

• CTEPH(NO SPECIFIC DRUGS ARE CURRENTLY APPROVED FOR CTEPH)



INTRODUCTION

• 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

PEA vs. LTx



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



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 8000 PEA have been performed worldwide so far with ≈ 30 % of all cases carried out by the San Diego Group



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



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



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



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 % – –



GENETIC MUTATIONS

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 %


• A PERMANENT INFERIOR VENA CAVA FILTER was placed before PEA in the majority (335/357) of patients

• Lifelong oral anticoagulation was prescribed after PEA


MARKED THROMBOPHILIA



REFERENCE



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



CLINIC

The clinical indication changes substantially

according to the different surgical treatment of CTEPH


• 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


CLINIC


• 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


HEMODYNAMIC

PRECAPILLARY PULMONARY HYPERTENSION



ANATOMY

• The surgical treatment depends on the localization of the lesions in the pulmonary arterial branches

• Lesions can be classified asPROXIMAL

DISTAL



PROXIMAL LESIONS



M.B. – 62 yrs M – Jul 2001 – PEA #64

Perfusion and ventilation scan

Pulmonary angiogram

Hemodynamic

mPAP 67CI 1.6PVR 1766



DISTAL LESIONS



S.S. – 31 yrs M – Sep 2002

Perfusion and ventilation scan

Pulmonary angiogram

Hemodynamic



• Growing single surgeon’s experience due to learning curve


OPERABILITY ASSESSMENT

Which lesions have to be considered as inoperable?

• Different operability assessments from different Centers


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)


CONTRAINDICATION TO PEA



P.B. – 60 yrs M – Jun 2002

Perfusion and ventilation scintigraphy

Pulmonary angiography

CT scan

Hemodynamic




BACKGROUND

• PEA is the treatment of choice for patients with CTEPH

• About only 10-15 Centers worldwide are performing PEA on a routine basis

• In expert hands, mortality ranges between 5% and 12% and technical failure is below 8%

• Early hemodynamic resultsare known to be excellent incase of successful operation



REFERENCE


• National referral program

• Begin: April 1994

• To date: 357 PEAs performed


OUR PROGRAM


55101

124

15

1916

28

7

47

215

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


PATIENTS’ REFERRALOF 357 PEAs



AMOUNT OF PATIENTS

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

Patients

65 PEAs in almost 8 yrs

65 PEAs in 1 yr



AMOUNT OF PATIENTSNEW EVALUATIONS

54

108

0

20

40

60

80

100

120

2004 2010

Pat

ien

ts

+ 100%



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%



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%



AMOUNT OF PATIENTSPEAs PERFORMED

22

65

0

10

20

30

40

50

60

70

2004 2010

PE

As

+ 195 %



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



PAVIA CTEPH PROGRAMJanuary, 1st – December, 31st 2010 231 pts

New Evaluations (108 pts) PEAs FUP (99 pts) Clinical Trials (23 pts) HLTx (1 pt)



• 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


• TUMOR (3 pts) - 3 pulmonary angiosarcoma

• ASSOCIATION WITH SEVERE EMPHYSEMA (1 pt) - 1 DLTx waiting-list



PAVIA CTEPH PROGRAMJanuary, 1st – June, 9th 2011 145 pts

New Evaluations (57 pts) PEAs FUP (69 pts) Clinical Trials (18 pts) DL/HLTx (1 pt)



• PROXIMAL LESIONS (29 pts) - 29 PEAs (4 pts evaluated in 2010) - 4 pts waiting for PEA

• DISTAL LESIONS (2 pts) - 2 medical therapy: 1 too old for DLTx 1 too early for DLTx


• TUMOR (1 pt) - 1 pulmonary angiosarcoma



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


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

25-DEC-1995

First DLTx for CTEPH


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


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



PEA POPULATIONOF 357 PEAs

Age 56 16 (11 84) years

Gender 171 M – 186 F

NYHA class 33 II – 165 III – 159 IV

Length III / IV 19 23 months

Urgent / Emergent 75 / 357

Oxygen therapy 174 / 357



RIGHT HEART CATHETERIZATIONOF 357 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



ECHOCARDIOGRAPHYOF 357 PEAs




• Tricuspid regurgitation Absent 2.7%

Mild18.9%

Moderate29.7%

Severe48.7%

• Abnormal interventricular septal motion Yes91.9%

No 8.1%

• Inferior vena cava collapsibility Yes40.5%

No59.5%

78.4%




Mean SD Range

LV-EDD 41 8 23 56 mm

LV-EDV 71 31 14 157 ml



ECHOCARDIOGRAPHY



CARDIAC MAGNETIC RESONANCEOF 244 PEA

Mean SD Range

RV-EDV 113 40 45 200 ml

RV-ESV 80 33 28 160 ml

RV-EF 33 11 10 57 %

RV-FWT 8.4 ± 1.3 6.5 – 11 mm



CARDIAC MAGNETIC RESONANCEOF 244 PEA

Mean SD Range

LV-EDV 88 29 38 156 ml

LV-ESV 50 21 20 109 ml

LV-EF 43 13 11 72 %



CARDIAC MAGNETIC RESONANCE



LUNG FUNCTIONOF 357 PEAs

Mean SD Range

FVC 91 18 39 148 %

FEV-1 84 18 40 131 %

DLCO 65 15 26 100 %



ARTERIAL BLOOD GASESOF 357 PEAs

Mean SD Range

Pa O2 65 10 43 97 mmHg

Pa CO2 31 7 24 43 mmHg

O2-sat 93 3 84 98 %



MODIFIED BRUCE TESTOF 357 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%


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%


CARDIOPULMONARY EXERCISE TESTINGOF 200 PEAs



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


• Median sternotomy• Cardio Pulmonary Bypass• Moderate hypotermia (24 °C)

• Circulatory arrest (7 min)• Reperfusion period (5 min)• Bilateral

J Thorac Cardiovasc Surg 1993;106:116-27


PULMONARY ENDARTERECTOMY


• Intra-wall dissection• Peripheral extension• Explore all branches

J Thorac Cardiovasc Surg 1993;106:116-27





SURGICAL INSTRUMENT


E.L. – 38 yrs M – Dec 1999 – PEA #42mPAP 43 20 (-53%)CO 3.3 6.9 (+109%)PVR 994 220 (-78%)


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%)



DISTAL LESIONS

JAMIESON TYPE IIILEARNING CURVE



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%)



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%)


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%)


JAMIESON TYPE III



OUT OF PROPORTION PH ?



B.R.A. - 72 yrs FmPAP 44CO 2.9RVEF 28PVR 1159



JAMIESON TYPE III



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




G.G. - 62 yrs FmPAP 51CO 2.6RVEF 19PVR 1415


OUT OF PROPORTION PH ?



JAMIESON TYPE III



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


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


CUMULATIVE PROPORTION SURVIVINGOF 357 PEAs

Operative mortality Global 32/357 (9.0%) NYHA II 0/33 (0.0%) NYHA III 8/165 (4.8%) NYHA IV 24/159 (15.1%)

Jan 08 – May 11 13/183 (7.1%)

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


0 12 24 36 48 60 72 84 96 108 120 132 144 156

M onths after PEA

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Percentage

1 3 3

8 6 .8 ± 2 .6

8 4 .7 ± 2 .8

8 3 .8 ± 2 .9 8 3 .8 ± 2 .9 8 3 .8 ± 2 .9 8 3 .8 ± 2 .9

1 1 3 9 3 5 4 3 4 1 4


CUMULATIVE PROPORTION SURVIVINGSURGERY vs. MEDICAL THERAPY

Riedel M. Chest 1982;81(2):151-8.

D’Armini A.M. Ital Heart J 2005;6(10):861-8.


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



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



FOLLOW-UP

In literature few data are reported on mid- and long- term cardiopulmonary function, particularly on exertion, and on clinical outcomes after PEA



FOLLOW-UP STUDY

• To monitor the natural history of these pts after PEA in terms of:– clinical status (by NYHA class)

– hemodynamic (by right heart catheterization)

– heart morphology and function (by ecocardiography and nuclear magnetic resonance)

– lung function (by spirometry, carbon monoxide transfer factor, arterial blood gas)

– exercise tolerance (by modified Bruce test and cardiopulmonary exercise testing)

– anatomy of arterial pulmonary vascular branches (by perfusion scinti scan, pulmonary angiography, multi detector angio-CT scan)



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)



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



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



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



ECHOCARDIOGRAPHYBefore PEA



ECHOCARDOGRAPHYFirst echo after PEA – POD #9



ECHOCARDIOGRAPHY3-months FUP after PEA



CARDIAC MAGNETIC RESONANCEBefore PEA First CMR after PEA – POD #6



CARDIAC MAGNETIC RESONANCE4-years FUP after PEAFirst CMR after PEA – POD #6



REVERSE RIGHT VENTRICULAR REMODELING



ARTERIAL OXYGEN PARTIAL PRESSURE

Arterial Oxygen Partial Pressure

0

10

20

30

40

50

60

70

80

90

100


Follow-up

mm

Hg

pp < 0.01 < 0.01




MODIFIED BRUCE TEST

Modified Bruce Test

0

100

200

300

400

500

600

700

800

900

1000


Follow-up

met

ers

pp < 0.01 < 0.01




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)



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



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


• 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


CONCLUSION



PULMONARY ENDARTERECTOMYIN THE ELDERLY

EXTENSION OFSURGICAL CRITERIA



AGE

• Apr 1994 – Dec 2002 → 10.8 % (9/83)

• Jan 2003 – June 2011 → 31.8 % (87/274)

Apr 1994 – June 2011 → 357 PEAs

261 (73.0%) PEAs performed in patients < 70 years old

96 (27.0%) PEAs performed in patients ≥ 70 years old



AGE

0%

20%

40%

60%

80%

100%

1994-1998 1999-2003 2004-2008 2009-2011

>= 70 yrs

< 70 yrs



CUMULATIVE PROPORTION SURVIVING

OF 261 vs. 96 PEAs

< 70 yrs >= 70 yrs0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180

Months after PEA

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0P

erc

en

tag

e

90.92.2

86.93.088.52.689.32.5

85.03.5 85.03.581.25.7

78.06.3 78.06.3


• Age did not affect the efficacy of PEA: PVR dramatically and equally decreased in both groups

• We never considered age as a contraindication to PEA

• However, operative mortality and perioperative morbidity were higher in patients age 70 and older: Gram negative infections and reperfusion edema were more severe in the elderly


CONCLUSIONS


• Compared to young subjects, elderly patients had a higher prevalence of major preoperative comorbidities, were sicker at the time of operation and had a reduced functional reserve of their vital organs

• However, this has to be expected in such patients:– age is a well identified independent risk factor in cardiac surgery

– in elderly patients the immune system response is less effective

– antibiotic therapy may lead to renal and hepatic impairment, increasing morbility and mortality


CONCLUSIONS



PAVIA PULMONARY ENDARTERECTOMY GROUPCTEPH

• 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

CTEPH, Surgical and Medical Therapy. CTEPH, Terapia Chirurgica e Medica

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