CTEPH CASI CLINICI

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

A peculiar case: a “seasoned veteran” in CTEPH

PULMONARY ENDARTERECTOMY: THE PAVIA EXPERIENCE

JAMIESON TYPE III

XX-XX-1949

ITALIANVARESE

HOUSE PAINTER

150 cm

48 KgSystemic arterial hypertension

Gastroesophageal reflux disease

P. F. #255




JAMIESON TYPE III

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




JAMIESON TYPE III

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




JAMIESON TYPE III

LUNG V/Q SCAN

VENTILATION PERFUSION




JAMIESON TYPE III

PULMONARY ANGIOGRAM




JAMIESON TYPE III

HRCT SCAN




JAMIESON TYPE III

DECEMBER 2005Enrollment in the BENEFIT study

(bosentan vs. placebo in inoperable forms of CTEPH)

Enrollment27-DEC-2005

End of study (16 weeks)28-APR-2006

Open label extension26-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




JAMIESON TYPE III

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

meters

15-FEB-2008 Withdrawal from DLTx waiting list

WHO III WHO II

BENEFIT-Open LabelBENEFIT




JAMIESON TYPE III

BILATERAL PULMONARY ENDARTERECTOMYRight: upper, middle and lower lobe

Left: 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)




JAMIESON TYPE III

BILATERAL PEA – SURGICAL SPECIMEN




JAMIESON TYPE III

• Invasive mechanical ventilation < 24 h

• Assisted normal breathing with continuous positive pressure (cPAP)

(to avoid reperfusion lung edema)

• ICU stay: 2 days (fast-track recovery program)

• Total postoperative hospital stay: 16 days

BILATERAL PEAEarly postoperative outcome




JAMIESON TYPE III

Preoperative27-NOV-2009

At discharge15-DEC-2009

3 months FUP26-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


WHO III I I

– 81 %

BILATERAL PEAHemodynamic results



JAMIESON TYPE IIIThe “seasoned veteran”

DIAGNOSIS

TRANSPLANT WAITING LIST

SPECIFIC MEDICAL THERAPY PULMONARY

ENDARTERECTOMY(Gold Standard)

SPECIFIC PAH-DRUG DISCONTINUATION


XX-XX-1934 (75 y)

ITALIANTURIN

PENSIONER

178 cm

72 Kg

P. B. #250

A peculiar case


PEA IN THE ELDERLY


MEDICAL HISTORY

• Congenital single kidney (right)• Sigmoid diverticulosis• Bilateral cataract• 2000: colonscopy polyp

removal

SEPTEMBER 2009Onset of mild dyspnea (WHO II) and right thoracic pain

OCTOBER 2009Acute dyspnea (WHO IV) → admission to the Emergency Ward

A peculiar case


PEA IN THE ELDERLY


A peculiar case


PEA IN THE ELDERLY

OCTOBER 2009Emergency ward diagnostic workup

• ECG: right ventricle overload

• Echocardiogram: dilation and hypokinesia of the right chambers

paradoxical movement of the interventricular septum

severe tricuspid regurgitation

severe pulmonary hypertension (sPAP 90 mmHg)

• HRCT scan: multiple bilateral segmental perfusion defects

CTEPH

NOVEMBER 2009Admission to our Division for operability assessment


A peculiar case


PEA IN THE ELDERLY

THROMBOPHILIA AND HYPERCOAGULABILITY

Laboratory findings

• Hyperhomocysteinemia

• Excess Factor VIII

• Prothrombin gene mutation (G20210A – Factor II)

• Homocysteine methabolism gene mutation (C677T – MTHFR)

• Homocysteine methabolism gene mutation (A1298C – MTHFR)

Echocolordoppler of the lower limbs

• Previous bilateral deep venous thrombosis


A peculiar case


PEA IN THE ELDERLY

OPERABILITY ASSESSMENT

Lung V/Q scan

• Massive bilateral perfusion defects(mainly at left upper lobe, lingula and right upper lobe)

• Quantitative perfusion map: left 38% – right 62%

Pulmonary angiogram

• Right upper lobe occlusion• Right inferior segmental middle lobe occlusion• Right posterior segmental lower lobe occlusion• Left anterior and posterior segmental upper lobe

occlusion• Left lower lobe occlusion


A peculiar case


PEA IN THE ELDERLY


HRCT scan


A peculiar case


PEA IN THE ELDERLY


Hemodynamic


RA 2

RV 78/0

PA 78/38/15

PCWP 5

CO 4.4

CI 2.3

RVEF 36

PVR 600

Serum-BNP 70

WHO III


A peculiar case


PEA IN THE ELDERLY

COLLATERAL FINDINGS

Echocolordoppler of the neck vessels

• 55% right common – internal carotid artery stenosis• 65% left common – internal carotid artery stenosis

Coronary angiogram

• Left main coronary artery ostial stenosis (80%)• LAD, 1st Diagonal, 2nd Diagonal and Circumflex

stenosis• Normal right coronary artery

Echocardiogram

• Moderate aortic regurgitation


A peculiar case


PEA IN THE ELDERLY

BILATERAL PULMONARY ENDARTERECTOMY

Right: upper, middle and lower lobeLeft: upper lobe, lingula and lower lobe

Moderate hypothermia (24° C)

Intermittent circulatory arrests right side: 50 minleft side: 30 mintotal time: 80 min

OPERATION

CORONARY ARTERY BYPASS GRAFTING

Right great saphenous vein on LAD and Circumflex

AORTIC VALVE REPLACEMENT

Carpentier-Edwards® Aortic Porcine Bioprosthesis


A peculiar case


PEA IN THE ELDERLY

BILATERAL PEA – SURGICAL SPECIMEN


• Invasive mechanical ventilation < 24 h

• Assisted normal breathing with continuous positive pressure (cPAP)

(to avoid reperfusion lung edema)

• ICU stay: 2 days (fast-track recovery program)

• Total postoperative hospital stay: 10 days

BILATERAL PEAEarly postoperative outcome

A peculiar case


PEA IN THE ELDERLY



At discharge18-NOV-2009

3 months FUP18-FEB-2010

RA 2 3 5 mmHg

RV 78/0 26/0 30/0 mmHg

PA 78/38/15 26/11/5 30/18/9 mmHg

PCWP 5 5 5 mmHg

CO 4.4 4.2 4.9 L/min

CI 2.3 2.2 2.7 L/min/m2

RVEF 36 40 36 %

PVR 600 114 212 dyn*s*cm-5


WHO III I I

– 65 %


A peculiar case


PEA IN THE ELDERLY

– 53 %

+ 11 %



WHO FUNCTIONAL CLASS II

A peculiar case

XX-XX-1983

ITALIANGENOA

STUDENT

162 cm

79 Kg

T. S. #108

Thrombosis risk factors

Sedentary lifestyle


MEDICAL HISTORY

• Obesity (BMI > 30 kg/m2) – Hormonal contraception – Active smoker ( 20 cig / day)• Recent car accident injuries without adequate venous thromboembolism prophylaxis• Coagulative disorders (hyperhomocysteinemia with C677T and A1298C gene mutation,

excess plasminogen activator inhibitor)

NOVEMBER 2003Acute pulmonary embolism

Right: partial embolic obstruction of the main pulmonary arteryLeft: total embolic occlusion of the main pulmonary artery



A peculiar case

THROMBOLYSIS




A peculiar case

APRIL 2004HRCT scan

Despite thrombolysis and 6 months of full oral anticoagulation therapy

Right: patent pulmonary arteryLeft: persisting subtotal embolic obstruction of the main pulmonary artery




A peculiar case

APRIL 2004Complete diagnostic workup

LUNG V/Q SCAN





A peculiar case


HEMODYNAMIC

Preoperative07-APR-2004

RA 6

RV 33/0

PA 29/20/12

PCWP 4

CO 6.7

CI 3.6

RVEF 55

PVR 191

Serum-BNP 20

WHO II




A peculiar case


PULMONARY ANGIOGRAM

• Radiologic features

• Failure of anticoagulation on the left obstruction

• Normal hemodynamic despite severe perfusion defect

DIFFERENTIAL DIAGNOSIS

LEFT PULMONARY ARTERY ANGIOSARCOMA ?




A peculiar case


DIFFERENTIAL DIAGNOSIS

LEFT PULMONARY ARTERY ANGIOSARCOMA ?

INTRAVASCULAR BIOPSY

• Unfortunately unsuccessful

• Undetermined diagnosis




A peculiar caseLEFT UNILATERAL PEA – INTRAOPERATIVE DIAGNOSIS

• At surgical inspection the endoluminal material appeared to be thromboembolic

• A left unilateral PEA was performed

• Diagnosis confirmed by histological examination

• Uncomplicated postoperative recovery

Invasive Mechanical Ventilation < 24 h

ICU stay 2 days

Total postoperative hospital stay 8 days




A peculiar case

Preoperative07-APR-2004

At discharge26-APR-2004

RA 6 3 mmHg

RV 33/0 29/0 mmHg

PA 29/20/12 29/13/2 mmHg

PCWP 4 5 mmHg

CO 6.7 7.5 L/min

CI 3.6 4.1 L/min/m2

RVEF 55 53 %

PVR 191 85 dyn*s*cm-5

Serum-BNP 20 91 pg/ml

WHO II I

– 55 %

LEFT UNILATERAL PEAHemodynamic results

– 35 %

+ 12 %




A peculiar case

DISCUSSION

• The hospitalization due to car accident injuries may have been complicated by a left pulmonary thromboembolism

• The patient could have been asymptomatic because of her sedentary lifestyle

• A second acute pulmonary thromboembolism on the right side could have revealed the previously asymptomatic disease

• Even if oral anticoagulation relieved most of symptoms and hemodynamic was normal, we deemed the patient a potential candidate for PEA

• The aim was to prevent the inexorable evolution of chronic thromboembolic lesions into CTEPH with vascular remodeling of the patent branches




A peculiar case

XX-XX-1944

ITALIANCREMONA

SPORTSMAN

180 cm

83 Kg

P. G. #146


MEDICAL HISTORY

• 1996: onset of exertional angina (negative cardiopulmonary exercise test)

• 2001: acute pulmonary embolism → oral anticoagulation therapy

• 2002 → 2006: regular echocardiographic controls showing the progressive onset of PH

• 2006: onset of exertional dyspnea (WHO II)



A peculiar case

MAY 2006Admission to our Division for operability assessment




A peculiar case

LUNG V/Q SCAN

MAY 2006Complete diagnostic workup





A peculiar case

HEMODYNAMIC

Preoperative11-MAY-2006

RA 4

RV 84/3

PA 84/45/20

PCWP 5

CO 2.9

CI 1.4

RVEF 18

PVR 1103

Serum-BNP 140

WHO II





A peculiar case

PULMONARY ANGIOGRAM





A peculiar case


HRCT SCAN




A peculiar caseBILATERAL PEA – SURGICAL SPECIMEN




A peculiar case


Preoperative11-MAY-2006

At discharge26-MAY-2006

4 years FUP12-MAR-2010

RA 4 0 5 mmHg

RV 84/3 15/0 29/0 mmHg

PA 84/45/20 15/12/6 29/18/9 mmHg

PCWP 5 3 5 mmHg

CO 2.9 3.9 4.5 L/min

CI 1.4 2.0 2.3 L/min/m2

RVEF 18 25 39 %

PVR 1103 185 231 dyn*s*cm-5


WHO II I I

– 79 %

– 60 %

– 55 %




A peculiar case

DISCUSSION

• Anticoagulation after the acute pulmonary embolism was probably not completely effective

• The incomplete resolution of organized pulmonary emboli resulted in progressive right heart failure

• Due to his high exercise tolerance, the patient became symptomatic only when the severe pulmonary hemodynamic jeopardized the left heart function (cardiac index of 1.4 L/min/m2)

• Hemodynamic and radiologic features of the disease were both impressive despite paucity of symptoms

CTEPH CASI CLINICI

Health & Medicine

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