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CHRONISCHE TROMBOEMBOLISCHE PULMONALE HYPERTENSIE (CTEPH) EPIDEMIOLOGIE, FYSIOPATHOLOGIE EN DIAGNOSTIEK MARION DELCROIX

PH CLASSIFICATION (NICE 2013) Group

Description

Group 1 Pulmonary arterial hypertension (PAH) Group 2 Pulmonary hypertension (PH) due to left heart disease Group 3 PH due to lung diseases and/or hypoxia Group 4 Chronic thromboembolic PH (CTEPH) and … Group 5 Unclear or multifactorial mechanisms Galie et al, EHJ and ERJ 2015

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Galie et al, EHJ and ERJ 2015

CTEPH DEFINITION mean PAP  25 mmHg abnormal ventilation-perfusion (V/Q) scan

1. 2. – –

3. 4.

one or more segmental-sized or larger mismatched perfusion defects

abnormal CT scan and/or abnormal pulmonary angiography showing typical findings of CTEPH at least 3 months of anticoagulation

Pepke-Zaba et al, Circulation 2011; 124: 1973

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CTEPH BURDEN IN PH CENTERS AND COUNTRIES Period

Number of patients

% CTEPH

Prevalence

Incidence

2001–2010

1344

18.0



0.3–3.7§

National Audit 2012 (UK)



7000

18.7

12.9–27.3

4.3–4.9

National Audit 2013 (UK)



7757

19.2

10.8–38.4

4.4–4.6

1998–2008

1028*

15.8

3.2

0.9

1998-2012

996

25





2008–2010

79†

41.8



1.1

Condliffe (UK)

2001–2006

469‡

100.0



1.4

CTEPH European registry

2008–2010

679‡

100.0



Up to 5.7#

ASPIRE registry (Sheffield, UK)

Spanish registry Swiss registry Portuguese registry

Registry including * only PAH and CTEPH cases, † only incident PAH and CTEPH cases, or ‡ only incident CTEPH patients; prevalence and incidence are expressed in cases per million inhabitants and per million inhabitants per year, respectively; § evolution over the years; # country with highest incidence (unpublished data)

Delcroix et al, Ann Am Thorac Soc 2015 (in press)

HISTORY OF PE IN CTEPH PATIENTS CTEPH risk factors(2) CTEPH associated

conditions(1)

Previous DVT (%)

56.1

Previous acute PE (%)

74.8

“Massive” PE (%)

40.8

Thrombolysis (%)

14.4

Recurrent PE (%)

32.8

Last PE to diagnosis (mo, median

12 [-2: 399]

[range])

Acute PE

ICOPER(3): 4% hemodynamically unstable, 13% thrombolysis, 25% previous VTE, 10% IVC filter RIETE(4): 1,6% massive (defined by BP230

6.5

HIT

1.9

ATIII deficiency

1.4

Other thrombophilias

18.5

Hyperhomocysteinemia/MTHF mutation

63.4

Pepke-Zaba et al, Circulation 2011; 124: 1973 ISHLT 2011

ANGIOGENESIS

Quarck et al, Eur Respir J 2015

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ANGIOGENESIS 120

120

100

100

Percent survival

Percent survival

Long-term survival PEA 2004-2009

80 60 40 20

Late Ang>0.8

80

p=0.01

60

Late Ang1 (CT) • sPAP >60 mmHg (TTE)

CTEPH prediction score5: CTEPH risk factors4 1. unprovoked PE Splenectomy, VA shunt for 2. hypothyroidism hydrocephaly, chronic inflammatory 3. symptom onset >2 weeks before PE diagnosis disorders, non-O blood group 4. RV dysfunction on CT or TTE (at 6 months) 5. no diabetes mellitus 6. no thrombolytic therapy or embolectomy

1. Pepke-Zaba J et al. Circulation 2011;124:1973–81. 2. Guérin L et al. Thromb Haemost 2014;112:598–605. 3. Klok FA et al. Thromb Res 2011;128:21–6. 4. Bonderman D et al. Eur Respir J 2009;33:325–31. 5. Klok et al. J Thromb Haemost 2015

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FACTORS SUGGESTIVE FOR CTEPH AFTER ACUTE PE At the time of index PE

In the follow up of acute PE

Massive and recurrent PE1

New or worsened dyspnea

PH already present2:

RV hypertrophy (ECG) and increased NTproBNP3

• RV/LV diameter >1 (CT) • sPAP >60 mmHg (TTE)

CTEPH prediction score5: CTEPH risk factors4 1. unprovoked PE Splenectomy, VA shunt for 2. hypothyroidism hydrocephaly, chronic inflammatory 3. symptom onset >2 weeks before PE diagnosis disorders, non-O blood group 4. RV dysfunction on CT or TTE (at 6 months) 5. no diabetes mellitus 6. no thrombolytic therapy or embolectomy

1. Pepke-Zaba J et al. Circulation 2011;124:1973–81. 2. Guérin L et al. Thromb Haemost 2014;112:598–605. 3. Klok FA et al. Thromb Res 2011;128:21–6. 4. Bonderman D et al. Eur Respir J 2009;33:325–31. 5. Klok et al. J Thromb Haemost 2015

82 y old F – CT (acute PE)

30

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82 y old F – ECG/NTproBNP

NTproBNP 1982 ng/L (