Screening for CETPH after acute pulmonary embolism: is it needed? Menno V. Huisman Department of Vascular Medicine LUMC Leiden

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1 Screening for CETPH after acute pulmonary embolism: is it needed? Menno V. Huisman Department of Vascular Medicine LUMC Leiden

2 Background CETPH Chronic Thrombo Embolic Pulmonary Hypertension intraluminal thrombus organization and fibrous stenosis or complete obliteration of the pulmonary arteries commonly associated with acute PE unknown pathogenesis of impaired clearance of acute thrombi and resulting vascular remodeling Hoeper MM. Circulation 2006

3 Incidence of CTEPH Reported incidence 0.1% - 8.8%

4 Incidence of CTEPH Reported incidence 0.1% - 8.8% Differences between previous studies: Selected patient cohorts Etiology of acute PE Comorbid conditions associated with PH Different diagnostic criteria Knowledge of this incidence important for patient management prolonged follow-up with specific screening programs for CTEPH?

5 Aims of the study To assess the incidence of CTEPH after symptomatic acute PE in an unselected large patient cohort To evaluate the efficacy of a screening program for CTEPH in patients after acute PE Klok et al Hematologica 2010; 95:

6 Methods: inclusion Consecutive patients diagnosed with PE in the period between and of a Dutch academic and affiliated teaching hospital intraluminal filling defects on pulmonary angiography or CTPA high probability VQ-scan intermediate probability VQ-scan in combination with objectively diagnosed DVT Irrespective of age, medical history or comorbid conditions

7 Methods: exclusion geographical inaccessibility precluding follow-up

8 Methods: procedures Review of original admission and outpatient charts 1. Established PH collection of relevant data 2. Mortality review of clinical course after the PE cause of death extracted from autopsy report or verified with treating physician or general practitioner 3. Survivors without PH telephonic interview of medical history and current clinical condition invitation single visit for echocardiography >1 year after PE

9 Methods: echocardiographic criteria for suspected PH 1. maximal tricuspid regurgitation velocity >2.8 m/s 2. estimated systolic Pap >35 mmhg 3. estimated mean Pap >25 mmhg 4. borderline value of criterion 1 or 2 in combination with a right ventricular TEI index > secondary changes associated with pulmonary hypertension 6. AcT <120 ms or AcT/RVET <0.40

10 Methods: work-up of patients with suspected PH VQ-scan HR-CT chest Pulmonary function tests Right heart catheterization for pressure measurements and conventional pulmonary angiography

11 Methods: diagnostic criteria for CTEPH mean Pap assessed by right heart catheterization > 25 mmhg normal pulmonary capillary wedge pressure abnormal perfusion scintigram and signs for distal or central CTEPH on conventional pulmonary angiography CTEPH was considered excluded in case of a normal VQ-scan

12 Results: patient demographics 877 diagnosed with acute PE 11 patients geographically inaccessible Included patients (n=866) Age, mean (SD), y 56 ± 19 Male sex (n, %) 410 (47) Idiopathic PE (n, %) 292 (34) Thrombolysis/Surgery/VCF 58 (6.7) COPD (n, %) 83 (9.6) Left sided heart failure (n, %) 42 (4.8)

13 Results: chart review and screening program 877 patients registered 11 patients excluded Chart review 19 PH 4 CTEPH 259 died 0 PH reported as cause of death 69 Autopsy or echocardiography negative for PH 0 CTEPH 588 eligible for Screening program Screening program (n=402) 392 PH ruled out 10 PH 0 CTEPH

14 Results: patients not in our screening program 186 screening not possible or denied 38 Recent echocardiography 0 CTEPH 148 No recent echocardiography 97 No time to be involved 0 exertional dyspnea 51 Age or comorbid conditions 10 exertional dyspnea, reasonably explained by comorbidity 0 CTEPH

15 Results: patients with CTEPH Sex Age Recurrent PE Risk factor first PE Localisation first PE Time from first PE (days) Mean PAP (mmhg) NYHA female 70 Yes idiopathic segmental II male 68 No idiopathic central III female 59 No idiopathic central III female 65 No idiopathic segmental III

16 Cumulative incidence of CTEPH (%) Results: incidence of CTEPH % ( ) 1.0 Idiopathic PE All cause PE % ( ) Time (years)

17 Discussion Very low yield of our screening program on top of routine clinical care Incidence of 0.57% lower compared to recent reports large unselected cohort all cases of CTEPH confirmed by right heart catheterization risk for underdiagnosis since not all 866 patients underwent echocardiography

18 Conclusions Incidence of CTEPH after PE was 0.57% incidence after idiopathic PE was 1.5% all cases diagnosed within 2 years all cases diagnosed by routine clinical care Routine screening after acute PE including echocardiography seems not warranted

19 Conclusions Routine clinical follow-up after acute PE should be performed during first two years Upon symptoms suggestive of PH (breathlessness, fatigue, weakness, angina, syncope, and abdominal distension) work-up is mandatory (PH-ESC guidelines 2009) Patients with acute pulmonary embolism showing signs of PH or RV dysfunction at any time during their hospital stay should receive a follow-up echocardiography after discharge (usually after 3 6 months) to determine whether or not PH has resolved Galiè et al Eur Heart J 2009; 30: 2528

20 Proposed diagnostic algorithm Klok et al Neth J Med 2010, in press

21 Acknowledgements FA Klok Vascular Medicine LUMC Leiden HW Vliegen Cardiology LUMC Leiden KW van Kralingen Pulmonology LUMC Leiden APJ van Dijk Cardiology Academic Hospital Nijmegen FH Heyning Internal Medicine Haaglanden Hospital The Hague This study was supported by an unrestricted research grant from Actelion Pharmaceuticals the Netherlands

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23 Methods: echocardiographic criteria for suspected PH 1. maximal tricuspid regurgitation velocity >2.8 m/s 2. estimated systolic pulmonary artery pressure >35 mmhg (maximal pressure gradient across the tricuspid valve calculated by the modified Bernoulli equation plus the estimated right atrium pressure) 3. estimated mean pulmonary artery pressure >25 mmhg (estimated systolic pressure plus 2 times enddiastolic pressure as estimated by pulmonary regurgitation enddiastolic velocity divided by 3

24 Methods: echocardiographic criteria for suspected PH 4. borderline value of criterion 1 or 2 in combination with a right ventricular TEI index >0.36 (isovolumic contraction time plus isovolumic relaxation time divided by ejection time) 5. secondary changes associated with pulmonary hypertension, e.g. systolic septal flattening, right ventricular hypertrophy or W-pattern in the right ventricular outflow curve 6. AcT (acceleration time ) <120 ms or AcT/RVET (right ventricular ejection time) <0.40

25 3 sub-groups Methods: statistical analysis all cause PE provoked or idiopathic PE Cumulative incidence of CTEPH after acute PE for all 3 study groups by Kaplan-Meier life table method. number of patient years was calculated from the date of the index event until diagnosis of CTEPH was established or ruled out or else until death had occurred