Chronic thromboembolic pulmonary hypertension (CTEPH) and the essential role of imaging specialists PP-ADE-ALL

Transcription

1 Chronic thromboembolic pulmonary hypertension (CTEPH) and the essential role of imaging specialists PP-ADE-ALL

2 CTEPH and the essential role of imaging specialists 1 Introduction, and signs, symptoms and history of CTEPH (Page 3-7) Introduction (Page 9-12) Echocardiography (Page 13-19) 2 CTEPH diagnosis (Page 9-42) 2.3 Ventilation/perfusion (V/Q) scintigraphy (Page 20-25) 3 Closing summary 2.4 Computed tomography pulmonary angiography (CTPA) (Page 26-36) (Page 43-45) 2.5 Right heart catheterization (RHC) (Page 37-39) 2.6 Catheter pulmonary angiography (Page 40-42)

3 1 Introduction, and signs, symptoms and history of CTEPH

4 Introduction CTEPH is underdiagnosed and undertreated 1,2 Early, accurate diagnosis is essential because without treatment, mortality is high 1,3 CTEPH is potentially curable with PEA surgery 3 Diagnosis can be challenging because clinical signs and symptoms may be non-specific, and known risk factors are not always present 4 The presence of comorbidities can also complicate the diagnosis 4 Accurate diagnosis of CTEPH requires multimodality imaging 4,5 This slide set aims to provide: An understanding of the signs and symptoms that may lead to a suspicion of CTEPH, as well as the association between acute PE and CTEPH An overview of the CTEPH diagnostic algorithm, and an insight into the different imaging modalities available to diagnose CTEPH and the information they each provide, in order to facilitate diagnosis PE, pulmonary embolism; PEA, pulmonary endarterectomy. 1. Klok FA et al. J Thromb Haemost 2016;14: Gall H et al. Eur Respir Rev 2017;doi: / Jenkins D. Eur Resp Rev 2012;21:123: Gopalan D et al. Eur Respir Rev 2017;26:160108; 5. Galiè N et al. Eur Respir J 2015;46:

5 Clinical signs and symptoms are non-specific or absent in early CTEPH Hemoptysis Dyspnea on exertion Chest pain Right heart failure (only evident in advanced disease) Fatigue, weakness Lower extremity edema Syncope Men and women are equally affected Galiè N et al. Eur Respir J 2015;46:

6 Most patients with CTEPH have a history of PE 1 A C U T E P E ~3% of patients develop CTEPH after surviving an acute PE 2 C T E P H BUT 25 30% of CTEPH patients have no history of acute PE 1,3 CTEPH should still be considered in patients without previous acute PE PE, pulmonary embolism. 1. Pepke-Zaba J et al. Circulation 2011;124: Ende-Verhaar YM et al. Eur Respir J 2017;49: Jamieson SW et al. Ann Thorac Surg 2003;76:

7 Patients with dyspnea and a history of PE should be screened for CTEPH 1 Patients should be screened to exclude CTEPH if they have: 1,2 Persistent/exercise-induced dyspnea after a minimum of 3 months of effective anticoagulation and A history of PE Additional risk factors in post-pe patients include: 2,3 Myeloproliferative disorders Chronic osteomyelitis History of malignancy Antiphospholipid antibodies Splenectomy Chronic central venous lines, Inflammatory bowel disease pacemakers, ventriculoatrial shunts PE, pulmonary embolism. 1. Galiè N et al. Eur Respir J 2015;46: Konstantinides SV et al. Eur Heart J 2014;35: Hoeper MM et al. Lancet Respir Med 2014;2:

8 2 CTEPH diagnosis

9 2.1 CTEPH diagnosis: Introduction

10 Under-referral of patients to expert CTEPH centers means patients are overlooked for potentially curative PEA surgery 1 Non-specific symptoms and signs 1 Delayed diagnosis (median 14 months) 2 Delayed treatment initiation 3 Increased risk of early death 3 PEA, pulmonary endarterectomy. 1. Mayer E, Idrees MM. Ann Thorac Med 2014; 9(Suppl 1):S Galiè N et al. Eur Respir J 2015;46: Gibbs JS. Heart 2001;86:i1 13.

11 All patients with suspected CTEPH should be referred to an expert center Non-specific symptoms and signs 1 Delayed diagnosis (median 14 months) 2 Delayed treatment initiation 3 Increased risk of early death 3 Referral to expert center Rapid confirmation of diagnosis, assessment of operability, and treatment 2 Rapid and accurate diagnosis of CTEPH is essential 2 PEA, pulmonary endarterectomy. 1. Mayer E, Idrees MM. Ann Thorac Med 2014; 9(Suppl 1):S Galiè N et al. Eur Respir J 2015;46: Gibbs JS. Heart 2001;86:i1 13.

12 2015 ESC/ERS guidelines: CTEPH diagnosis Symptoms, signs, history suggestive of CTEPH Echocardiographic probability of PH High or intermediate probability of PH V/Q scan a Mismatched perfusion defects? YES CTEPH possible NO CTEPH ruled out; work-up for PH/PAH Refer to PH/CTEPH expert center CT pulmonary angiography a CT pulmonary angiography alone may miss diagnosis of CTEPH. CT, computed tomography; ERS, European Respiratory Society; ESC, European Society of Cardiology; V/Q, ventilation/perfusion. Galiè N et al. Eur Respir J 2015;46: Right heart catheterization +/ Pulmonary angiography

13 2.2 Echocardiography

14 Transthoracic echocardiography (TTE) is used as an initial screening tool for PH TRV at rest PH signs Probability of PH ERS, European Respiratory Society; ESC, European Society of Cardiology; LA, left atrium; LV left ventricle; PA, pulmonary artery; PASP, pulmonary artery systolic pressure; RA, right atrium; RAP, right atrial pressure; RV, right ventricle; TRV, tricuspid regurgitation velocity. Galiè N et al. Eur Respir J 2015;46:

15 Transthoracic echocardiography (TTE) is used as an initial screening tool for PH TRV at rest The ESC/ERS Guidelines recommend using the continuous wave Doppler measurement of peak TRV (and not the estimated PASP due to the inaccuracies of RAP estimation) as the main variable for assigning the echocardiographic probability of PH PH signs Peak TRV Probability of PH ERS, European Respiratory Society; ESC, European Society of Cardiology; LA, left atrium; LV left ventricle; PA, pulmonary artery; PASP, pulmonary artery systolic pressure; RA, right atrium; RAP, right atrial pressure; RV, right ventricle; TRV, tricuspid regurgitation velocity. Galiè N et al. Eur Respir J 2015;46:

16 Transthoracic echocardiography (TTE) is used as an initial screening tool for PH TRV at rest PH signs Probability of PH Signs from at least two different categories (A/B/C) should be present to alter the level of echo probability of PH Inferior vena cava and right atrium Inferior cava diameter >21 mm width with decreased inspiratory collapse (<50% with a sniff or <20% with quiet inspiration) RA area (end-systole) >18 cm 2 A The ventricles B A Pulmonary artery RV outflow Doppler acceleration time <105 ms and/or mid-systolic notching Early diastolic pulmonary regurgitation velocity >2.2 m/s PA diameter >25 mm RV/LV basal diameter ratio >1.0 Flattening of the interventricular septum (LV eccentricity index >1.1 in systole and/or diastole) ERS, European Respiratory Society; ESC, European Society of Cardiology; LA, left atrium; LV left ventricle; PA, pulmonary artery; PASP, pulmonary artery systolic pressure; RA, right atrium; RAP, right atrial pressure; RV, right ventricle; TRV, tricuspid regurgitation velocity. Galiè N et al. Eur Respir J 2015;46:

17 Transthoracic echocardiography (TTE) is used as an initial screening tool for PH TRV at rest PH signs Probability of PH LOW PH probability Peak TRV 2.8 m/s or not measurable No other PH signs present on echo INTERMEDIATE PH probability Peak TRV 2.8 m/s or not measurable Other PH signs present on echo Peak TRV m/s No other PH signs present on echo HIGH PH probability Peak TRV m/s Other PH signs present on echo Peak TRV >3.4 m/s (other PH signs on echo not required) Image presented with kind permission from William Auger, University of California San Diego La Jolla, CA, USA. ERS, European Respiratory Society; ESC, European Society of Cardiology; LA, left atrium; LV left ventricle; PA, pulmonary artery; PASP, pulmonary artery systolic pressure; RA, right atrium; RAP, right atrial pressure; RV, right ventricle; TRV, tricuspid regurgitation velocity. Galiè N et al. Eur Respir J 2015;46:

18 Example echocardiographic findings in CTEPH Right ventricular hypertrophy in a patient with CTEPH Flattening of the interventricular septum in a patient with CTEPH Images presented with kind permission from William Auger, University of California San Diego La Jolla, CA, USA. RA, right atrium; RV, right ventricle.

19 Echocardiography in CTEPH: Summary RA, right atrium; RV, right ventricle. Galiè N et al. Eur Respir J 2015;46:

20 2.3 Ventilation/perfusion (V/Q) scintigraphy

21 V/Q scintigraphy is used to rule out CTEPH V/Q scintigraphy Guideline-recommended initial screening tool for work-up of CTEPH after diagnosis of PH G uideline r ecommendation f or V/Q is based on: 100% 93.7% 96.5% SENSITIVITY SPECIFICITY ACCURACY V/Q, ventilation/perfusion. Galiè N et al. Eur Respir J 2015;46:

22 V/Q scintigraphy typically consists of two tests 1. A ventilation scan Patient breathes in an inert gas (xenon-133, or krypton-81m) or radiolabeled aerosol (technetium- 99m-DTPA, or technetium-99mlabeled Technegas) 2. A perfusion scan Technetium-99m macroaggregated human albumin is injected into a peripheral vein Gamma camera acquires the images for both the ventilation and perfusion scans DTPA, diethylene triamine pentaacetic acid; V/Q: ventilation/perfusion. Bajc M et al. Eur J Nucl Med Mol Imaging 2009;36:

23 A normal perfusion pattern excludes CTEPH Ventilation: NORMAL Perfusion: NORMAL Normal ventilation and perfusion patterns/absence of mismatched perfusion defects rules out CTEPH In IPAH and PVOD, V/Q scintigraphy results tend to be normal, or show non-segmental defects Images presented with kind permission of Alan Maurer, Temple University, Philadelphia, PA, USA. IPAH, idiopathic pulmonary hypertension; LAO, left anterior oblique; LPO, left posterior oblique; POST, posterior; PVOD, pulmonary veno-occlusive disease; RAO, right anterior oblique; RPO, right posterior oblique; V/Q, ventilation/perfusion. Galiè N et al. Eur Respir J 2015;46:

24 Segmental perfusion defects suggest CTEPH Ventilation: NORMAL Perfusion: DEFECTS If CTEPH is present, at least one, but commonly several, segmental wedge-shaped perfusion defects are seen, and a V/Q mismatch is noted 1 Perfusion defects seen with V/Q scintigraphy are not always due to pulmonary emboli, and other pulmonary vascular disease must be ruled out 2 Images presented with kind permission of Alan Maurer, Temple University, Philadelphia, PA, USA. ANT, anterior; LAO, left anterior oblique; LPO, left posterior oblique; POST, posterior; RAO, right anterior oblique; RPO, right posterior oblique; V/Q, ventilation/perfusion. 1. Auger WR et al. Pulm Circ 2012;2: Hoeper MM et al. Lancet Respir Med 2014;2:

25 Ventilation/perfusion scintigraphy: Summary CTPA, computed tomography pulmonary angiography. 1. Galiè N et al. Eur Respir J 2015;46: Tunariu N et al. J Nucl Med 2007;48: Waxman A et al. J Nucl Med 2017;58:13N 15N. 4. D Armini AM. Eur Respir Rev 2015;24:253 62

26 2.4 Computed tomography pulmonary angiography (CTPA)

27 CTPA may help to identify complications of CTEPH 1 CTPA Can reveal signs of CTEPH in the heart, pulmonary arteries and lungs 2 I n e x p e r t h a n d s, C T PA f o r t h e d i a g n o s i s o f C T E P H h a s : 1, % % SENSITIVITY (lobar) SPECIFICITY (lobar) % 93 99% SENSITIVITY (segmental) SPECIFICITY (segmental) CTPA, computed tomography pulmonary angiography. 1. Galiè N et al. Eur Respir J 2015;46: Auger WR et al. Pulm Circ 2012;2: Gopalan D et al. Eur Respir Rev 2017;26:

28 Potential signs of CTEPH 1 Pulmonary arteries Eccentric organized thrombi (eccentric intraluminal filling defects) that form an obtuse angle with the vessel wall 2,3 Dilatation of the central pulmonary arteries 2,3 Total occlusions (pouch defects), or partial occlusions 3 Stenoses, indicated by variability in the size of lobar and segmental-level vessels, and/or irregular vessel caliber 2,3 Intraluminal fibrous bands or webs 2,3 SUMMARY Lungs Mosaic perfusion pattern of the lung parenchyma 2,3 Large bronchial artery collaterals 2,3 Residual scars from infarcts 3,4 Heart Right ventricular hypertrophy 2 Thickening of the right ventricular wall 2 1. Galiè N et al. Eur Respir J 2015;46: Dogan H et al. Diagn Interv Radiol 2015;21: Gopalan D et al. Ann Am Thorac Soc 2016;13:S222 S Schwickert HC et al. Radiology 1994;191:

29 CTPA signs of CTEPH in the heart Enlarged right ventricle, and thickening of the outer right ventricular wall Prominent moderator band (septomarginal trabecula; arrow) Image presented with kind permission from William Auger, University of California San Diego La Jolla, CA, USA. CTPA, computed tomography pulmonary angiography.

30 CTPA signs of CTEPH in the pulmonary arteries Dilatation of central pulmonary arteries Central pulmonary artery diameter >29 mm in men and >27 mm in women is abnormal, 1 and is one sign of PH 2 Total and partial occlusions Images presented with kind permission from Deepa Gopalan, Cambridge University and Imperial College Hospitals, London, UK; and Narinder Paul, London Health Sciences Centre University Hospital, London, ON, Canada. CTPA, computed tomography pulmonary angiography. 1. Truong QA et al. Circ Cardiovasc Imaging 2012;5: Galiè N et al. Eur Respir J 2015;46:

31 CTPA signs of CTEPH in the pulmonary arteries Eccentric thrombus (red arrow) Eccentric lining thrombus (white arrow) and intraluminal web (red arrow) Images presented with kind permission from Deepa Gopalan, Cambridge University and Imperial College Hospitals, London, UK; and William Auger, University of California San Diego La Jolla, CA, USA. CTPA, computed tomography pulmonary angiography.

32 CTPA signs of CTEPH in the pulmonary arteries: Appearance of acute clots differs from chronic clots Chronic, post-embolic fibrotic tissue appears different to fresh clots on CTPA: A recent clot is typically surrounded by contrast Chronic clots are adherent to the wall of the pulmonary arteries, with the contrast collecting centrally 1 Clot surrounded by contrast agent in central PA Images presented with kind permission from Deepa Gopalan, Cambridge University and Imperial College Hospitals, London, UK; and William Auger, University of California San Diego La Jolla, CA, USA. CTPA, computed tomography pulmonary angiography; PA, pulmonary artery. 1. Wittram C et al. Am J Roentgenol 2006;186:S421 9.

33 CTPA signs of CTEPH in the pulmonary arteries Stenosis in the left lower lobe Stenosis with post-stenotic dilatation Images presented with kind permission from Deepa Gopalan, Cambridge University and Imperial College Hospitals, London, UK; and William Auger, University of California San Diego La Jolla, CA, USA. CTPA, computed tomography pulmonary angiography.

34 CTPA signs of CTEPH in the pulmonary arteries Intraluminal web Intraluminal web Images presented with kind permission from Narinder Paul, London Health Sciences Centre University Hospital, London, ON, Canada; and William Auger, University of California San Diego La Jolla, CA, USA. CTPA, computed tomography pulmonary angiography.

35 CTPA signs of CTEPH in the lungs Large bronchial collaterals Mosaic attenuation, and peripheral wedge-shaped infarct Images presented with kind permission from Deepa Gopalan, Cambridge University and Imperial College Hospitals, London, UK. CTPA, computed tomography pulmonary angiography.

36 Computed tomography pulmonary angiography: Summary 1. Proceedings from 6th World Symposium on Pulmonary Hypertension (WSPH) 2018, reference awaited. 2. Galiè N et al. Eur Respir J 2015;46: Gopalan D et al. Eur Respir Rev 2017;26: D Armini AM. Eur Respir Rev 2015;24: Auger WR et al. Pulm Circ 2012;2: Kim NH et al. J Am Coll Cardiol 2013;62:D92 9.

37 2.5 Right heart catheterization (RHC)

38 RHC is essential to confirm the diagnosis of CTEPH Invasive procedure Catheter placed in the right heart and pulmonary artery, usually through a central vein e.g. right internal jugular vein 1 Rarely associated with serious complications; depends on patient s clinical status and operator experience 1 Technically demanding Should be limited to expert centers to obtain high-quality results while minimizing risk to patients 2 Low morbidity (1.1%) and mortality (0.055%) in expert centers 2 Assesses hemodynamics Enables direct and accurate measurement of the condition of the right heart and pulmonary vessels 1 Indirectly provides information about the left heart 1 Confirms CTEPH diagnosis 2 Guides treatment decisions and surgical eligibility 2 Preoperative and immediate postoperative PVR is a long-term predictor prognosis 2 *IC, class I recommendation (is recommended/indicated), level of evidence C (consensus of opinion of the experts and/or small studies, retrospective studies, registries). PVR, pulmonary vascular resistance; RHC, right heart catheterization. 1. Grymuza M et al. Adv Interv Cardiol 2017: ; 2. Galiè N et al. Eur Respir J 2015;46:

39 Right heart catheterization: Summary Galiè N et al. Eur Respir J 2015;46:

40 2.6 Catheter pulmonary angiography

41 Catheter pulmonary angiography: can determine operability, or suitability for balloon pulmonary angioplasty Left to right: front, lateral, right anterior oblique, and left anterior oblique views of pulmonary vasculature in a patient with CTEPH Images presented with kind permission of Tetsuya Fukuda, National Cerebral and Cardiovascular Center, Osaka, Japan. Galiè N et al. Eur Respir J 2015;46:

42 Catheter pulmonary angiography: Summary BPA, balloon pulmonary angioplasty; PEA, pulmonary endarterectomy. Galiè N et al. Eur Respir J 2015;46:

43 3 Closing summary 43

44 Summary CTEPH is an underdiagnosed, undertreated and life-threatening condition that can potentially be cured by surgery if accurately diagnosed 1 3 Early, accurate diagnosis is essential because without treatment, mortality is high 4 Imaging specialists play a crucial role in prompt and accurate diagnosis, and in assessing operability 5 A multimodality approach is required, comprising echocardiography, V/Q scintigraphy, CTPA, conventional pulmonary angiography, and right heart catheterization 6 1. Klok FA et al. J Thromb Haemost 2016;14: Gall H et al. Eur Respir Rev 2017;doi: / D'Armini AM et al. Eur Respir Rev 2015;24: Jenkins D. Eur Resp Rev 2012;21:123: Galiè N et al. Eur Respir J 2015;46: Gopalan D et al. Eur Respir Rev 2017;26:

45 CTEPH Scan for it, for the chance to surgically cure it PP-ADE-ALL