What are the guideline sources, guidelines and references for Chronic thromboembolic pulmonary hypertension ?
Guideline sources The following summarized guidelines for the evaluation and management of chronic thromboembolic pulmonary hypertension (CTEPH) are prepared by our editorial team based on guidelines from the European Society of Cardiology (ESC/ERS 2022), the European Respiratory Society (ERS 2021), the Canadian Cardiovascular Society (CCS/CTS 2020), the European Society of Cardiology (ESC/ESR 2016), the American Heart Association (AHA 2011), and the Canadian Thoracic Society (CTS 2010). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/recCN97vmQBHSoqXD 1/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway Definition: consider viewing patients with symptoms attributable to post-thrombotic deposits within pulmonary arteries as having chronic thromboembolic pulmonary disease, with or without pulmonary hypertension. Use CTEPH term in patients with pulmonary hypertension. E Epidemiology: recognize that CTEPH is a rare and underdiagnosed complication of pulmonary embolism and upon first presentation may be misclassified as acute pulmonary embolism. E Show 3 more Pathophysiology: Recognize that two types of vascular lesions exist in CTEPH: proximal fibrotic obstruction in large elastic pulmonary arteries secondary microvasculopathy in pulmonary vessels < 500 mcm. E Show 2 more Indications for screening: As per ERS 2021 guidelines, insufficient evidence to recommend screening for CTEPH in asymptomatic patients with specific risk factors. I As per ESC 2016 guidelines, do not screen asymptomatic survivors of pulmonary embolism for CTEPH. D As per CTS 2010 guidelines, avoid obtaining routine echocardiography or follow-up imaging (V/Q, CT or MRI) to screen for CTEPH in asymptomatic patients following an acute VTE. D Indications for testing: As per ESC 2022 guidelines: Obtain diagnostic evaluation to assess for CTEPH/chronic thromboembolic pulmonary disease in patients with persistent or new-onset dyspnea or exercise intolerance after pulmonary embolism. B Refer symptomatic patients with mismatched perfusion lung defects beyond 3 months of anticoagulation or acute pulmonary embolism to a pulmonary hypertension/CTEPH center, after considering the results of echocardiography, BNP/N-terminal pro-BNP, and/or cardiopulmonary exercise testing. B As per ERS 2021 guidelines, evaluate patients with acute pulmonary embolism with risk factors or radiological findings of CTEPH for early diagnosis of CTEPH. E Show 2 more As per CCS 2020 guidelines: Assess for CTEPH with echocardiography and V/Q lung scan in patients with residual dyspnea or exercise intolerance after at least 3 months of uninterrupted anticoagulation post- acute pulmonary embolism. B Assess the possibility of CTEPH with initial V/Q lung scan in patients being evaluated for pulmonary hypertension. B As per AHA 2011 guidelines: Obtain evaluation for CTEPH in patients presenting with unexplained dyspnea, exercise intolerance, or clinical evidence of right-sided HF, with or without prior history of symptomatic VTE. B https://web.pathway.md/diseases/recCN97vmQBHSoqXD 2/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway Consider obtaining echocardiography 6 weeks after an acute pulmonary embolism to screen for persistent pulmonary hypertension to predict the development of CTEPH. C 2. Diagnostic investigations Echocardiography: obtain echocardiography as the test of choice in patients with suspected CTEPH. Consider using the Leiden CTEPH rule-out criteria to exclude the presence of CTEPH and/or to establish an alternative diagnosis. E Perfusion imaging: As per ESC 2022 guidelines, obtain V/Q or perfusion lung scan to assess for CTEPH in patients with unexplained pulmonary hypertension. B As per ERS 2021 guidelines: Obtain V/Q scintigraphy as the most effective screening tool to exclude chronic thromboembolic pulmonary disease. Consider obtaining V/Q SPECT over planar imaging. Consider reprojecting 3D planar images from SPECT, because the transition from planar imaging to SPECT may not be easy for clinicians unfamiliar with the 3D anatomy. E Do not favor alternative perfusion techniques (such as dual energy CT and magnetic resonance perfusion) over V/Q, because they are more technically challenging and expensive with limited availability and lacking multicenter validation. D As per CTS 2010 guidelines, obtain nuclear V/Q lung scanning instead of CT pulmonary angiography as a screening test to rule out the possibility of CTEPH in patients diagnosed with pulmonary hypertension. B Show 2 more Pulmonary angiography: As per ESC 2022 guidelines: Obtain CT pulmonary angiography in the evaluation of patients with suspected CTEPH. B Consider obtaining digital subtraction angiography in the evaluation of patients with CTEPH. C As per ERS 2021 guidelines, obtain high-quality CT pulmonary angiogram for the diagnosis of proximal CTEPH. E Show 3 more As per CTS 2010 guidelines, consider obtaining positive CT pulmonary angiogram routinely to assess the anatomical extent of surgically accessible CTEPH. C Show 2 more Cardiopulmonary exercise testing: Consider obtaining cardiopulmonary exercise testing to exclude the presence of CTEPH and/or to establish an alternative diagnosis. E Consider obtaining cardiopulmonary exercise testing and exercise-right heart catheterization to contribute to the definition of chronic thromboembolic pulmonary disease helping to identify the https://web.pathway.md/diseases/recCN97vmQBHSoqXD 3/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway main cause of exercise limitation in the presence of comorbidities and in patients without resting pulmonary hypertension. E Antiphospholipid antibodies: obtain testing for antiphospholipid syndrome in patients with CTEPH. B 3. Diagnostic procedures Right heart catheterization: perform right heart catheterization in all patients with suspected CTEPH to confirm the hemodynamic diagnosis of precapillary pulmonary hypertension and to assess the severity of pulmonary hypertension. B 4. Respiratory support Supplemental oxygen: Administer supplemental oxygen in patients with CTEPH exhibiting hypoxemia at rest. Insufficient evidence to recommend for or against the use of supplemental oxygen in patients with CTEPH manifesting isolated nocturnal and/or exertional oxygen desaturation. I 5. Medical management General principles: As per ESC 2022 guidelines: Review all patients with CTEPH by a CTEPH team for the assessment of multimodal management. B Consider offering a multimodality approach in patients with persistent pulmonary hypertension after pulmonary endarterectomy and in patients with inoperable CTEPH. C As per ERS 2021 guidelines: Ensure a multidisciplinary team approach considering pulmonary endarterectomy, medical therapy and balloon pulmonary angioplasty for optimal treatment of patients with CTEPH. E Insufficient evidence to recommend any eligibility criteria for multimodal therapy, which is dependent on the expertise and judgment of each individual CTEPH center. Conduct patient selection for multimodal therapy in expert centers through a multidisciplinary team approach. I As per CCS 2020 guidelines, refer all potential CTEPH patients to a local expert pulmonary hypertension center for the establishment of a formal diagnosis of CTEPH and assessment for the most appropriate treatment. B PAH-specific pharmacotherapy, indications: As per ERS/ESC 2022 guidelines, consider initiating off-label drugs approved for pulmonary arterial hypertension in symptomatic patients with inoperable CTEPH. C https://web.pathway.md/diseases/recCN97vmQBHSoqXD 4/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway As per ERS 2021 guidelines, consider discontinuing pulmonary hypertension medications after successful balloon pulmonary angioplasty and/or pulmonary endarterectomy. E As per AHA 2011 guidelines: Consider initiating pulmonary arterial hypertension (WHO group I)-specific pharmacotherapy in patients with CTEPH unfit for surgery (because of comorbidities or patient choice) or having residual pulmonary hypertension after surgical treatment not amenable to repeat pulmonary endarterectomy at an experienced center. C Do not initiate pulmonary arterial hypertension (WHO group I)-specific pharmacotherapy in lieu of pulmonary endarterectomy and do not delay evaluation for pulmonary endarterectomy in patients with objectively proven CTEPH being or possibly being surgical candidates at an experienced center. D PAH-specific pharmacotherapy, combination therapy: As per ERS/ESC 2022 guidelines, consider initiating a combination therapy of soluble guanylate cyclase stimulators/PDE5 inhibitors, endothelin receptor antagonists, or parenteral prostacyclin analogs in patients with inoperable CTEPH. C As per ERS 2021 guidelines, initiate oral combination therapy in patients with CTEPH with severe hemodynamic compromise. E As per CTS 2010 guidelines, do not initiate routine combination pulmonary hypertension-specific therapy in patients with inoperable CTEPH or residual pulmonary hypertension after pulmonary endarterectomy. D Soluble guanylate cyclase stimulators: As per ESC 2022 guidelines, initiate riociguat, a soluble guanylate cyclase stimulator, in symptomatic patients with inoperable CTEPH. B Landmark trials: CHEST-1 In patients with inoperable chronic thromboembolic pulmonary hypertension, or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy, riociguat was superior to placebo with respect to improvement in 6-minute walk distance at week 16. Hossein-Ardeschir Ghofrani et al. N Engl J Med. 2013 Jul 25. As per CCS 2020 guidelines, initiate riociguat monotherapy in all patients with symptomatic inoperable CTEPH. B Endothelin receptor antagonists: Consider initiating endothelin receptor antagonist (bosentan) monotherapy to improve symptoms and exercise capacity, short-term hemodynamics and, possibly, survival in patients with symptomatic inoperable CTEPH. C Insufficient evidence to assess the potential benefits of other endothelin receptor antagonists, such as sitaxsentan and ambrisentan. I https://web.pathway.md/diseases/recCN97vmQBHSoqXD 5/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway Phosphodiesterase-5 inhibitors: Consider initiating PDE5 inhibitor (sildenafil) monotherapy in patients with symptomatic, inoperable CTEPH, to improve short-term hemodynamics and WHO functional class and, possibly, long-term exercise capacity and health-related quality of life. C Insufficient evidence to assess the potential benefits of other phosphodiesterase type 5 inhibitors, such as tadalafil and vardenafil. I Prostanoids: As per ESC 2022 guidelines, consider initiating treprostinil SC in patients with inoperable CTEPH, WHO functional class III-IV. C As per CTS 2010 guidelines, consider initiating parenteral prostanoids (such as IV epoprostenol or SC/IV treprostinil) monotherapy in patients with symptomatic, inoperable CTEPH. C Anticoagulation: As per ESC 2022 guidelines, initiate lifelong, therapeutic doses of anticoagulation in all patients with CTEPH. B Show 2 more As per ERS 2021 guidelines: Initiate lifelong anticoagulation, with vitamin K antagonists as the mainstay of anticoagulant therapy, in patients with CTEPH. E Recognize that direct OACs are increasingly used, with no safety issues reported yet. Do not use direct OACs in patients with antiphospholipid syndrome. E As per AHA 2011 guidelines, initiate indefinite therapeutic anticoagulation in patients with objectively proven CTEPH, if not contraindicated. B As per CTS 2010 guidelines, initiate chronic anticoagulants in all patients with CTEPH, including patients not undergoing pulmonary endarterectomy and patients post- pulmonary endarterectomy. B Other medications: Do not use high-dose CCBs in patients with CTEPH. D Avoid initiating routine digoxin therapy in patients with CTEPH. D Recognize that digoxin may be of some limited benefit in selected patients with CTEPH with RV failure or atrial arrhythmias. 6. Nonpharmacologic interventions Rehabilitation: As per ERS 2021 guidelines: Offer rehabilitation, in hospital or home-based settings, in patients with inoperable CTEPH. E Consider offering a carefully monitored, low-dose rehabilitation program as standard of care in patients with CTEPH after pulmonary endarterectomy or balloon pulmonary angioplasty. E https://web.pathway.md/diseases/recCN97vmQBHSoqXD 6/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway As per CTS 2010 guidelines, consider offering cardiopulmonary exercise rehabilitation in patients with CTEPH. C 7. Therapeutic procedures Balloon pulmonary angioplasty: As per ESC 2022 guidelines, consider performing balloon pulmonary angioplasty in technically operable patients with a high proportion of distal disease and an unfavorable risk-benefit ratio for pulmonary endarterectomy. C Show 2 more As per ERS 2021 guidelines, insufficient evidence regarding the role of balloon pulmonary angioplasty as bridging therapy before pulmonary endarterectomy in patients with mixed surgically accessible and inaccessible lesions. I Show 7 more As per CCS 2020 guidelines, consider performing balloon pulmonary angioplasty in patients with CTEPH ineligible for or declining pulmonary endarterectomy. C As per CTS 2010 guidelines, consider performing balloon pulmonary angioplasty to improve pulmonary hemodynamics, WHO functional class and exercise capacity in patients with surgically accessible CTEPH ineligible for pulmonary endarterectomy. C Inferior vena cava filter placement: insufficient evidence to recommend for or against the routine use of IVC filters in patients with CTEPH. I 8. Perioperative care Preoperative pharmacotherapy: As per ERS 2021 guidelines, insufficient evidence that preoperative pharmacotherapy is beneficial in patients with operable CTEPH. Consider initiating pulmonary hypertension-targeted drugs as bridging therapy to pulmonary endarterectomy in selected high-risk patients (with high preoperative pulmonary vascular resistance) after multidisciplinary team assessment in expert centers. I As per CTS 2010 guidelines, consider initiating pre-pulmonary endarterectomy treatment with IV epoprostenol in selected patients with severe surgically accessible CTEPH (WHO functional class III or IV with a pulmonary vascular resistance > 1200 dyn s/cm and/or RV failure) to improve hemodynamics and operability. C Show 2 more 9. Surgical interventions Pulmonary endarterectomy: https://web.pathway.md/diseases/recCN97vmQBHSoqXD 7/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway As per ESC 2022 guidelines, perform pulmonary endarterectomy as the treatment of choice in patients with CTEPH and fibrotic obstructions within pulmonary arteries accessible by surgery. B As per ERS 2021 guidelines, consider performing surgery for segmental and subsegmental disease in expert, high-volume centers, recognizing that there is probably considerable anatomical overlap between balloon pulmonary angioplasty and pulmonary endarterectomy. E Show 3 more As per CCS 2020 guidelines, evaluate all patients with CTEPH for pulmonary endarterectomy in consultation with a pulmonary endarterectomy center. B As per AHA 2011 guidelines, obtain prompt evaluation for pulmonary endarterectomy in patients with objectively proven CTEPH, even if symptoms are mild. B As per CTS 2010 guidelines: Perform pulmonary endarterectomy as the treatment of choice in patients with surgically- accessible CTEPH. B Consider performing pulmonary endarterectomy in patients with distal CTEPH on an individual basis at a center experienced with pulmonary endarterectomy. C Lung transplantation: As per CCS 2020 guidelines, refer patients with CTEPH with persistent severe pulmonary hypertension (NYHA class III or IV, and/or RV failure) despite maximal medical therapy for lung transplantation assessment. B As per CTS 2010 guidelines, refer inoperable patients with CTEPH or patients experiencing residual pulmonary hypertension post-pulmonary endarterectomy and remaining in WHO functional class III or IV, despite optimal medical therapy, for evaluation for lung transplantation. B Ensure early referral as there can be significant delays until transplantation. 10. Follow-up and surveillance Post-PEA management, pharmacotherapy: As per ERS/ESC 2022 guidelines: Initiate riociguat in symptomatic patients with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. B Consider initiating treprostinil SC in patients with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. C As per ERS 2021 guidelines, initiate riociguat (an oral guanylate cyclase stimulator) or treprostinil (a subcutaneous prostacyclin analog) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. E As per CTS/CCS 2020 guidelines, initiate riociguat monotherapy in all patients with residual/recurrent CTEPH post-pulmonary endarterectomy. B As per CTS 2010 guidelines: https://web.pathway.md/diseases/recCN97vmQBHSoqXD 8/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway Consider initiating the following monotherapies in patients with symptomatic, residual pulmonary hypertension after pulmonary endarterectomy: endothelin receptor antagonist (bosentan) PDE5 inhibitor (sildenafil) parenteral prostanoid (IV epoprostenol or subcutaneous/IV treprostinil), if oral pulmonary hypertension-specific therapy was ineffective or not tolerated. C Insufficient evidence to assess the potential benefits of other endothelin receptor antagonists (such as sitaxsentan and ambrisentan), other phosphodiesterase type 5 inhibitors (such as tadalafil and vardenafil) and oral (such as beraprost) or inhaled (such as iloprost or treprostinil) prostanoids in patients with CTEPH. I Post-PEA management, follow-up: As per ERS/ESC 2022 guidelines, obtain long-term follow-up after pulmonary endarterectomy and balloon pulmonary angioplasty, as well as in patients with CTEPH established on medical therapy. B As per CTS 2010 guidelines, consider offering long-term follow-up in a pulmonary hypertension expert center in patients with CTEPH after pulmonary endarterectomy. C Likelihood Ratios Pertinent positives The following findings increase the probability of chronic thromboembolic pulmonary hypertension in adults. -1 Finding LR+ Value Presence of findings of pulmonary embolism 51 Presence of findings of pulmonary embolism 9.6 Pertinent negatives The following findings decrease the probability of chronic thromboembolic pulmonary hypertension in adults. -1 Finding LR- Value Absence of findings of pulmonary embolism 0 Absence of findings of pulmonary embolism 0.5 References 1. Marion Delcroix, Adam Torbicki, Deepa Gopalan et al. ERS statement on chronic thromboembolic pulmonary hypertension. Eur Respir J. 2021 Jun 17;57 6 2002828. Open 2. Sanjay Mehta, Doug Helmersen, Steeve Provencher et al. Diagnostic evaluation and management of chronic thromboembolic pulmonary hypertension: a clinical practice guideline. Can Respir J. Nov-Dec https://web.pathway.md/diseases/recCN97vmQBHSoqXD 9/10 6/23/23, 3:26 AM Chronic thromboembolic pulmonary hypertension Pathway 2010;17 6 301 34. Open 3. Naushad Hirani, Nathan W Brunner, Ali Kapasi et al. Canadian Cardiovascular Society/Canadian Thoracic Society Position Statement on Pulmonary Hypertension. Can J Cardiol. 2020 Jul;36 7 977 992. Open 4. Marc Humbert, Gabor Kovacs, Marius M Hoeper et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43 38 3618 3731. Open 5. Michael R Jaff, M Sean McMurtry, Stephen L Archer et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123 16 1788 830. Open 6. Gali N, Humbert M, Vachiery JL et al. 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. Rev Esp Cardiol Engl Ed). 2016 Feb;69 2 177. Open https://web.pathway.md/diseases/recCN97vmQBHSoqXD 10/10