|Group 1: PAH|
|1.1 Idiopathic PAH|
|1.2 Heritable PAH|
|1.3 Drug- and toxin-induced PAH|
|1.4 PAH associated with:|
|1.4.1 Connective tissue disease|
|1.4.2 HIV infection|
|1.4.3 Portal hypertension|
|1.4.4 Congenital heart disease|
|1.5 PAH long-term responders to calcium channel blockers|
|1.6 PAH with overt features of venous/capillaries (PVOD/PCH) involvement|
|1.7 Persistent PH of the newborn syndrome|
|Group 2: PH due to left heart disease|
|2.1 PH due to heart failure with preserved LVEF|
|2.2 PH due to heart failure with reduced LVEF|
|2.3 Valvular heart disease|
|2.4 Congenital/acquired cardiovascular conditions leading to postcapillary PH|
|Group 3: PH due to lung diseases and/or hypoxia|
|3.1 Obstructive lung disease|
|3.2 Restrictive lung disease|
|3.3 Other lung disease with mixed restrictive/obstructive pattern|
|3.4 Hypoxia without lung disease|
|3.5 Developmental lung disorders|
|Group 4: PH due to pulmonary artery obstructions|
|4.1 Chronic thromboembolic PH|
|4.2 Other pulmonary artery obstructions|
|Group 5: PH with unclear and/or multifactorial mechanisms|
|5.1 Hematological disorders|
|5.2 Systemic and metabolic disorders|
|5.4 Complex congenital heart disease|
Echocardiography for identification of PH
- Rudski L.G.
- Lai W.W.
- Afilalo J.
- et al.
- 1.We recommend transthoracic echocardiography for initial assessment of all patients with clinically suspected PH or unexplained dyspnea (Strong Recommendation, Moderate-Quality Evidence).
- 2.We recommend a complete echocardiographic assessment when PH is suspected, including estimation of sPAP using the TRV jet, measurement of inferior vena cava size, and degree of inspiratory collapse, as well as assessment of “secondary” signs of PH, such as RA or right ventricular (RV) enlargement, RV hypertrophy, septal flattening, and RV dysfunction (Strong Recommendation, Moderate-Quality Evidence).
- Rudski L.G.
- Lai W.W.
- Afilalo J.
- et al.
Echocardiography for classification of PH
- 3.We recommend transthoracic echocardiography in all PH patients to detect any abnormality of left-sided chambers or valves, which can indicate the possibility of postcapillary PH (Strong Recommendation, Moderate-Quality Evidence).
Echocardiographic prognosticators in patients with PH
- 4.We recommend that PH patients should have baseline and follow-up echocardiograms that measure systolic PAP, RA size, tricuspid regurgitation severity, and presence/severity of pericardial effusion. Additionally, indices of RV systolic function should be assessed using tricuspid annular plane systolic excursion, S', or RV index of myocardial performance, with free wall strain using 2-dimensional speckle tracking being a recommended method in laboratories with suitable equipment and expertise (Strong Recommendation, Moderate-Quality Evidence).
Recognizing PAH in high-risk groups
- 5.We recommend annual echocardiography and measurement of lung diffusing capacity for carbon monoxide to screen for PH in all patients with scleroderma (Strong Recommendation, Low-Quality Evidence).
- 6.We recommend echocardiography to screen for PH in all patients with portal hypertension being assessed for liver transplantation (Strong Recommendation, Low-Quality Evidence).
Right heart catheterization
- 7.We recommend RHC in all patients with suspected PAH or CTEPH to confirm the hemodynamic diagnosis of precapillary PH and to assess the severity of PH (Strong Recommendation, Moderate-Quality Evidence).
- 8.We recommend RHC in PH patients be performed only in centres with technical expertise and experience to accurately assess cardiopulmonary hemodynamics and to diagnose and appropriately classify the cause of PH (Strong Recommendation, Low-Quality Evidence).
|Reference level||The choice of reference level can lead to substantial variability in measured pressures, with mid-thoracic height best approximating the level of the left atrium.|
51See Figure 4A
|Wedge pressure||Mean PAP may be determined at end-expiration, or with a mean throughout the respiratory cycle. With obesity or obstructive lung disease, respiratory swings in intrathoracic pressure can be substantial, affecting interpretation of the hemodynamics. Computer-derived mean pressure measurements instead of end-expiratory pressures can change PH classification in 25%-30% of patients.|
53We recommend pressure measurement at end expiration. Values should be taken using examination of traces containing several respiratory cycles and not the automatic digital estimation by recording devices. See Figure 4B
|When a reliable assessment of pulmonary arterial wedge pressure is not possible, consideration should be given to performing a left heart catheterization to obtain a left ventricular end diastolic pressure. This is particularly important when mixed etiologies of PH are being considered|
|Cardiac output||Although most accurate, the direct Fick estimation of cardiac output is rarely feasible. The commonly used techniques are the TD and indirect Fick methods. They correlate with direct Fick, but the agreement between methods is only fair.|
55Because TD correlates better with RV function and mortality, it should be used
Cardiac magnetic resonance
- Kreitner K.F.
- Wirth G.M.
- Krummenauer F.
- et al.
- 9.We suggest CMR imaging in PAH patients when accessible to assess right ventricle size and function to help guide management (Weak Recommendation, Moderate-Quality Evidence).
Approach to Management of PAH
|Parameter||Low risk||Intermediate risk||High risk|
|WHO/NYHA functional class||I-II||III||IV|
|Clinical right heart failure||Absent||Absent||Present|
|Six-minute walk distance, m||> 440||165-440||< 165|
|NT pro-BNP, ng/mL or BNP, ng/L||< 300||300-1400||> 1400|
|< 50||50-300||> 300|
|RAP, mm Hg||< 8||8-14||> 14|
|SvO2||> 65%||60%-65%||< 60%|
|Echo/CMR RA area, cm2||< 18||18-26||> 26|
|Pericardial effusion||None||None or minimal||Present|
|CPET peak VO2, mL/min/kg||> 15||11-15||< 11|
|VE/VCO2 slope||< 36||36-45||> 45|
- Galie N.
- Humbert M.
- Vachiery J.L.
- et al.
- 10.We recommend general supportive (education, psychosocial support, contraception) measures in all PAH patients to improve understanding and self-management (Strong Recommendation, Low-Quality Evidence).
- 11.We recommend supervised exercise rehabilitation be considered in PAH patients to improve functional capacity and health-related quality of life (HRQoL; Strong Recommendation, Moderate-Quality Evidence).
- 12.We suggest general medical therapeutic measures (diuretics for volume overload, and oxygen for resting hypoxemia) in all PAH patients (Weak Recommendation, Low-Quality Evidence).
- 13.We suggest systemic anticoagulation with warfarin in selected PAH patients (idiopathic PAH [IPAH], heritable PAH [HPAH], drug- and toxin-induced [DPAH]) in the absence of elevated bleeding risk (Weak Recommendation, Low-Quality Evidence). We recommend against systemic anticoagulation in patients with PAH associated with connective tissue disease, CHD, portal hypertension, and HIV (Strong Recommendation, Low-Quality Evidence).
Calcium channel blockers
- 14.We recommend acute vasodilator testing (with inhaled NO, intravenous [I.V.] epoprostenol or adenosine) in selected PAH patients (IPAH, HPAH, DPAH) (Strong Recommendation, Low-Quality Evidence). Marked vasodilator responsiveness (decrease in mean PAP ≥ 10 mm Hg to < 40 mm Hg and stable/increased cardiac output) identifies a subgroup of patients more likely to respond to high-dose CCBs, which should be initiated in PH expert centres (Strong Recommendation, Low-Quality Evidence).
PAH-targeted medications available in Canada
|Drug family||Drug name||Trade name||Route of delivery||Typical dosing||Notable side effects||Health Canada approved||Recommendation/level of evidence|
|Prostacyclin pathway agents||Epoprostenol||Flolan, Caripul||Continuous I.V. infusion||10-30 ng/kg/min||Flushing, headache, diarrhea, jaw/bone pain, nausea, hypotension, central line complications, rebound PH||Yes||I/A|
|Treprostinil||Remodulin||Continuous SC/I.V. infusion||20-80 ng/kg/min||Flushing, headache, diarrhea, jaw/bone pain, nausea, hypotension, infusion site pain||Yes||I/B, IIb/C|
|Orenitram||Oral||3-6 mg bid||Flushing, headache, diarrhea, jaw/bone pain, nausea||No||IIb/B|
|Tyvaso||Inhaled||54 μg qid||Flushing, headache, diarrhea, jaw/bone pain, nausea, cough||No||I/B|
|Iloprost||Ventavis||Inhaled||5 μg 6-9 times daily||No||I/B|
|Selexipag||Uptravi||Oral||200-1600 μg bid||Flushing, headache, diarrhea, jaw/bone pain, nausea||Yes||I/B|
|Endothelin receptor antagonists||Bosentan||Tracleer, generic||Oral||125 mg bid||Hepatotoxicity, anemia, fluid retention||Yes||I/A|
|Ambrisentan||Volibris||Oral||10 mg daily||Yes||I/A|
|Macitentan||Opsumit||Oral||10 mg daily||Yes||I/B|
|Nitric oxide pathway agents||Sildenafil||Revatio, generic||Oral||20-80 mg tid||Headaches, flushing, fluid retention||Yes||I/A|
|Tadalafil||Adcirca||Oral||40 mg daily||Yes||I/B|
|Riociguat||Adempas||Oral||1.0-2.5 mg tid||Hypotension, headache, gastroesophageal reflux||Yes||I/B|
- Galie N.
- Humbert M.
- Vachiery J.L.
- et al.
Endothelin receptor antagonists
NO-cyclic GMP pathway
Risk-Based Assessment and Treatment Strategies
- Galie N.
- Humbert M.
- Vachiery J.L.
- et al.
- Galie N.
- Humbert M.
- Vachiery J.L.
- et al.
Limitations to Access and Therapy
- 15.We recommend that all PAH patients be assessed in a recognized PH centre to confirm the diagnosis, direct institution of PH-targeted therapies, and evaluate the response to treatment (Strong Recommendation, Low-Quality Evidence).
- 16.We recommend initial oral monotherapy (ERA, PDE-5i, or sGCs) only in low-risk (Table 3) treatment-naive PAH patients (Strong Recommendation, High-Quality Evidence).
- 17.We recommend initial dual oral combination therapy in intermediate-risk treatment-naive PAH patients (Strong Recommendation, High-Quality Evidence).
- 18.We recommend initial combination therapy including I.V. epoprostenol in high-risk patients who are candidates for such therapies (Strong Recommendation, Low-Quality Evidence). We suggest initial combination therapy including I.V./subcutaneous treprostinil in high-risk PAH patients who are candidates for such therapies (including NYHA FC IV; Weak Recommendation, Low-Quality Evidence).
- 19.We recommend regular reassessment of all PAH patients using a panel of measures (clinical, functional, hemodynamic, and/or right ventricle size/function [Table 3]; Strong Recommendation, Low-Quality Evidence).
|Initial/combination therapy||No head-to-head trials or other data support any specific initial choice of therapy|
|There are no reliable factors that predict the likelihood of an individual PAH patient responding to any specific individual or combination of PH-targeted medical therapies|
|The use of ambrisentan with tadalafil in upfront combination therapy is supported by a randomized controlled trial.|
90Other initial therapeutic combinations can be considered, but are less well supported by clinical evidence
|Most combinations of the 4 classes of drugs are acceptable, except the combination of PDE-5i and sGCs which is contraindicated because of the risk of systemic hypotension|
|Follow-up||Regular comprehensive reassessment of all PAH patients is required to assess response to therapy and establish individual risk for poor clinical outcomes (worse functional status, hospitalization, need for transplantation, or death)|
|Reassessment should occur within 3-4 months of institution of initial therapy or any change in therapy. In PAH patients who achieve low-risk status, reassessment could be every 6-12 months, depending on geographic access to the PH expert centre|
|Risk assessment||The definitions of low, intermediate, and high-risk patient profiles include a combination of measures that appear in Table 3. There are various approaches on the parameters that should be included and how to weight each parameter|
|After initial PH-targeted therapy, patients who improve to low-risk status upon reassessment can safely continue their individual current maintenance therapy|
Which PH Patients Should Not Be Treated With PAH-targeted Medications?
PH due to left heart disease (group II PH)
- Fang J.C.
- DeMarco T.
- Givertz M.M.
- et al.
- 20.We recommend that the management of patients with group II PH should focus on efforts to optimize ventricular filling pressures and treat the underlying causes of and contributors to left heart disease (Strong Recommendation, Low-Quality Evidence).
- 21.We recommend against the routine use of PAH-targeted therapies in patients with group II (post-capillary) PH (Strong Recommendation, Low-Quality Evidence).
PH due to lung disease and/or hypoxia (group III PH)
- 22.We recommend against routine RHC and against the use of PAH-targeted therapy in patients with mild-moderate World Health Organization group III PH in the absence of RV failure (Strong Recommendation, Moderate-Quality Evidence).
- 23.We suggest that patients with moderate-severe World Health Organization group III PH (and/or features of RV failure) be referred to a PH centre (Strong Recommendation, Low-Quality Evidence).
Diagnosis and Management of CTEPH (Group IV PH)
- 24.We recommend that patients with residual dyspnea or exercise intolerance after at least 3 months of uninterrupted anticoagulation post acute PE be assessed for CTEPH with echocardiography and V/Q lung scan (Strong Recommendation, Low-Quality Evidence).
- 25.We strongly recommend that the possibility of CTEPH be assessed with initial V/Q scanning in patients being evaluated for PH (Strong Recommendation, Low-Quality Evidence).
- 26.We recommend that all potential CTEPH patients be referred to a local expert PH centre for establishment of a formal diagnosis of CTEPH and assessment for the most appropriate treatment (Strong Recommendation, Moderate-Quality Evidence)
- 27.We strongly recommend that all CTEPH patients be evaluated for PEA in consultation with a PEA centre (Strong Recommendation, Moderate-Quality Evidence).
- 28.We recommend treatment with riociguat monotherapy in all patients with symptomatic inoperable or residual/recurrent CTEPH post-PEA (Strong Recommendation, Moderate-Quality Evidence). We do not currently recommend for or against combination PH-targeted medical therapy in CTEPH patients.
- 29.We suggest CTEPH patients who are ineligible for or decline PEA be considered for balloon pulmonary angioplasty (Weak Recommendation, Low-Quality Evidence).
- •Either planar or single-photon emission computed tomography or nuclear V/Q scan are acceptable modalities to screen for CTEPH.
- •A normal perfusion (Q) scan effectively rules out the possibility of CTEPH.
- •A negative computed tomography pulmonary angiogram does not effectively rule out CTEPH.
- •Macitentan improved hemodynamics and functional capacity in inoperable CTEPH patients in a phase II placebo-controlled RCT,121but is not yet Health Canada-approved for this indication.
- •Low-quality evidence suggests a possible benefit of other PAH-targeted medications (I.V. epoprostenol, subcutaneous treprostinil, oral bosentan, oral sildenafil).124
Lung Transplantation for PH
- 30.We recommend that PH patients (especially PAH and CTEPH) with persistent severe PH (NYHA FC III or IV, and/or RV failure) despite maximal medical therapy be referred for lung transplantation assessment (Strong Recommendation, Moderate-Quality Evidence).
- 31.We suggest that PH patients with refractory RV failure and/or hemodynamic instability be considered for extracorporeal life support as a “bridge” to definitive PH therapy (Weak Recommendation, Moderate-Quality Evidence).
- Increasing incidence and prevalence of World Health Organization groups 1 to 4 pulmonary hypertension: a population-based cohort study in Ontario, Canada.Circ Cardiovasc Qual Outcomes. 2018; 11e003973
- A global view of pulmonary hypertension.Lancet Respir Med. 2016; 4: 306-322
- Haemodynamic definitions and updated clinical classification of pulmonary hypertension.Eur Respir J. 2019; 53: 1801913
- Pulmonary arterial hypertension in France: results from a national registry.Am J Respir Crit Care Med. 2006; 173: 1023-1030
- An epidemiological study of pulmonary arterial hypertension.Eur Respir J. 2007; 30: 104-109
- GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926
- Diagnosis of pulmonary hypertension.Eur Respir J. 2019; 53: 1801904
- An evidence-based approach to screening and diagnosis of pulmonary hypertension.Can J Cardiol. 2015; 31: 382-390
- Definitions and diagnosis of pulmonary hypertension.J Am Coll Cardiol. 2013; 62: D42-D50
- Diagnosis of chronic thromboembolic pulmonary hypertension: a Canadian Thoracic Society clinical practice guideline update.Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2019; 3: 177-198
- Canadian Cardiovascular Society and Canadian Thoracic Society position statement on pulmonary arterial hypertension.Can J Cardiol. 2005; 21: 909-914
- Pulmonary Vascular Diseases Committee of the American College of Chest Physicians. Pulmonary Hypertension Care Center Network: improving care and outcomes in pulmonary hypertension.Chest. 2017; 151: 749-754
- Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.J Am Soc Echocardiogr. 2010; 23 ([quiz: 786-8]): 685-713
- Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension.Am J Respir Crit Care Med. 2009; 179: 615-621
- Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical practice.Chest. 2011; 139: 988-993
- Mean pulmonary artery pressure using echocardiography in chronic thromboembolic pulmonary hypertension.Circ J. 2016; 80: 1259-1264
- Addressing the controversy of estimating pulmonary arterial pressure by echocardiography.J Am Soc Echocardiogr. 2016; 29: 93-102
- Right heart hemodynamics in pulmonary hypertension- an echocardiography and catheterization study.Circ J. 2016; 80: 2019-2025
- Derivation of mean pulmonary artery pressure from noninvasive parameters.J Am Soc Echocardiogr. 2013; 26: 464-468
- An alternative echocardiographic method to estimate mean pulmonary artery pressure: diagnostic and clinical implications.J Am Soc Echocardiogr. 2009; 22: 814-819
- A clinical and echocardiographic score to identify pulmonary hypertension due to HFpEF.J Card Fail. 2017; 23: 29-35
- Noninvasive identification of left-sided heart failure in a population suspected of pulmonary arterial hypertension.Eur Respir J. 2015; 46: 422-430
- Assessment of right ventricular adaptability to loading conditions can improve the timing of listing to transplantation in patients with pulmonary arterial hypertension.J Heart Lung Transplant. 2015; 34: 319-328
- Efficacy of right ventricular free-wall longitudinal speckle-tracking strain for predicting long-term outcome in patients with pulmonary hypertension.Circ J. 2013; 77: 756-763
- Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension.Circ Cardiovasc Imaging. 2013; 6: 711-721
- Prognostic value of right ventricular strain using speckle-tracking echocardiography in pulmonary hypertension: a systematic review and meta-analysis.Can J Cardiol. 2018; 34: 1069-1078
- Incidence and significance of pericardial effusion in patients with pulmonary arterial hypertension.Can J Cardiol. 2013; 29: 678-682
- Prognostic value of pericardial effusion on serial echocardiograms in pulmonary arterial hypertension.Echocardiography. 2015; 32: 1471-1476
- Echocardiographic assessment of estimated right atrial pressure and size predicts mortality in pulmonary arterial hypertension.Chest. 2015; 147: 198-208
- Tricuspid regurgitation duration correlates with cardiovascular magnetic resonance-derived right ventricular ejection fraction and predict prognosis in patients with pulmonary arterial hypertension.Eur Heart J Cardiovasc Imaging. 2014; 15: 18-23
- Echocardiographic and hemodynamic predictors of survival in precapillary pulmonary hypertension: seven-year follow-up.Circ Cardiovasc Imaging. 2015; 8e002107
- Pulmonary hypertension in HIV.Can J Cardiol. 2019; 35: 288-298
- Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study.Ann Rheum Dis. 2014; 73: 1340-1349
- A comparison of the predictive accuracy of three screening models for pulmonary arterial hypertension in systemic sclerosis.Arthritis Res Ther. 2015; 17: 7
- Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension.Arthritis Rheum. 2013; 65: 3194-3201
- Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis.Ann Rheum Dis. 2012; 71: 1980-1983
- Prevalence and risk factors for left ventricular diastolic dysfunction in a scleroderma cohort.Scand J Rheumatol. 2017; 46: 281-287
- Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era.Am J Respir Crit Care Med. 2008; 177: 108-113
- Updated clinical classification of pulmonary hypertension.J Am Coll Cardiol. 2013; 62: D34-D41
- Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups.Am J Transplant. 2008; 8: 2445-2453
- Portopulmonary hypertension: results from a 10-year screening algorithm.Hepatology. 2006; 44: 1502-1510
- Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.Liver Transpl. 2000; 6: 453-458
- Screen for portopulmonary hypertension, especially in liver transplant candidates.Cleve Clin J Med. 2008; 75: 121-136
- Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry.Chest. 2010; 137: 376-387
- The diagnostic accuracy of Doppler echocardiography in assessment of pulmonary artery systolic pressure: a meta-analysis.Echocardiography. 2013; 30: 258-265
- Diagnostic accuracy of tissue Doppler index E/e' for evaluating left ventricular filling pressure and diastolic dysfunction/heart failure with preserved ejection fraction: a systematic review and meta-analysis.J Am Heart Assoc. 2016; 5e002530
- Association of borderline pulmonary hypertension with mortality and hospitalization in a large patient cohort: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.Circulation. 2016; 133: 1240-1248
- Prognostic effect and longitudinal hemodynamic assessment of borderline pulmonary hypertension.JAMA Cardiol. 2017; 2: 1361-1368
- Mild elevation of pulmonary arterial pressure as a predictor of mortality.Am J Respir Crit Care Med. 2018; 197: 509-516
- Borderline mean pulmonary artery pressure in patients with systemic sclerosis: transpulmonary gradient predicts risk of developing pulmonary hypertension.Arthritis Rheum. 2013; 65: 1074-1084
- Zero reference level for right heart catheterisation.Eur Respir J. 2013; 42: 1586-1594
- Reliance on end-expiratory wedge pressure leads to misclassification of pulmonary hypertension.Eur Respir J. 2014; 44: 425-434
- Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension.Am Heart J. 2012; 163: 589-594
- Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation.Can Respir J. 2012; 19: 261-266
- Noninvasive and simple assessment of cardiac output and pulmonary vascular resistance with whole-body impedance cardiography is useful for monitoring patients with pulmonary hypertension.Circ J. 2013; 77: 2383-2389
- Comparison of thermodilution and indirect Fick cardiac outputs in pulmonary hypertension.Int J Cardiol. 2018; 258: 228-231
- Thermodilution vs estimated Fick cardiac output measurement in clinical practice: an analysis of mortality from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and Vanderbilt University.JAMA Cardiol. 2017; 2: 1090-1099
- Noninvasive assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension by high temporal resolution phase-contrast MRI: correlation with simultaneous invasive pressure recordings.Circ Cardiovasc Imaging. 2013; 6: 722-729
- Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry.JACC Cardiovasc Imaging. 2013; 6: 1036-1047
- A non-invasive assessment of cardiopulmonary hemodynamics with MRI in pulmonary hypertension.Magn Reson Imaging. 2015; 33: 1224-1235
- Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis.Eur Radiol. 2016; 26: 3771-3780
- Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving pulmonary arterial hypertension-targeted therapy: the EURO-MR study.Circ Cardiovasc Imaging. 2014; 7: 107-114
- Signs of right ventricular deterioration in clinically stable patients with pulmonary arterial hypertension.Chest. 2015; 147: 1063-1071
- Right atrial volume and reservoir function are novel independent predictors of clinical worsening in patients with pulmonary hypertension.J Heart Lung Transplant. 2015; 34: 414-423
- Right atrial emptying fraction non-invasively predicts mortality in pulmonary hypertension.Int J Cardiovasc Imaging. 2016; 32: 1121-1130
- ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension.Eur Respir J. 2019; 53: 1800332
- Thrombotic arteriopathy and anticoagulation in pulmonary hypertension.Chest. 2006; 130: 545-552
- Effect of warfarin treatment on survival of patients with pulmonary arterial hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).Circulation. 2015; 132: 2403-2411
- A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.Chest. 2010; 138: 1093-1100
- The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension.N Engl J Med. 1992; 327: 76-81
- Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension.Circulation. 2005; 111: 3105-3111
- Changing face of pulmonary arterial hypertension in Canada.Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2017; 1: 242-252
- An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry.Chest. 2012; 142: 448-456
- A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.N Engl J Med. 1996; 334: 296-301
- Selexipag for the treatment of pulmonary arterial hypertension.N Engl J Med. 2015; 373: 2522-2533
- Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.Lancet. 2001; 358: 1119-1123
- Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.Circulation. 2008; 117: 3010-3019
- Macitentan and morbidity and mortality in pulmonary arterial hypertension.N Engl J Med. 2013; 369: 809-818
- Sildenafil citrate therapy for pulmonary arterial hypertension.N Engl J Med. 2005; 353: 2148-2157
- Tadalafil therapy for pulmonary arterial hypertension.Circulation. 2009; 119: 2894-2903
- Authors of CHEST-1 and PATENT-1. Riociguat for pulmonary hypertension.N Engl J Med. 2013; 369: 2268
- Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.N Engl J Med. 2013; 369: 319-329
- 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).Eur Respir J. 2015; 46: 903-975
- Prognostic value of follow-up hemodynamic variables after initial management in pulmonary arterial hypertension.Circulation. 2018; 137: 693-704
- Risk assessment in pulmonary arterial hypertension.Eur Respir J. 2018; 51: 1800279
- A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension.Eur Heart J. 2018; 39: 4175-4181
- Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model.Eur Respir J. 2017; 50: 1700740
- Predicting survival in patients with pulmonary arterial hypertension: the REVEAL Risk Score Calculator 2.0 and comparison with ESC/ERS-based risk assessment strategies.Chest. 2019; 156: 323-337
- Risk stratification and medical therapy of pulmonary arterial hypertension.Eur Respir J. 2019; 53: 1801889
- Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension.N Engl J Med. 2015; 373: 834-844
- CADTH Therapeutic Reviews. Drugs for Pulmonary Arterial Hypertension: Comparative Efficacy, Safety, and Cost-Effectiveness.Canadian Agency for Drugs and Technologies in Health, Ottawa, Ontario2015
- Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.Eur Respir J. 2017; 50: 1700889
- The minimally invasive MitraClip procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function.Anaesthesia. 2014; 69: 860-867
- Prognostic significance of right ventricular dysfunction in patients with functional mitral regurgitation undergoing MitraClip.Am J Cardiol. 2016; 118: 1717-1722
- Meta-analysis of outcomes and evolution of pulmonary hypertension before and after transcatheter aortic valve implantation.Am J Cardiol. 2017; 119: 91-99
- Left ventricular dyssynchrony predicts right ventricular remodeling after cardiac resynchronization therapy.J Am Coll Cardiol. 2005; 46: 2264-2269
- Continuous flow left ventricular assist device implant significantly improves pulmonary hypertension, right ventricular contractility, and tricuspid valve competence.J Card Surg. 2013; 28: 770-775
- The effect of left ventricular assist device therapy in patients with heart failure and mixed pulmonary hypertension.Int J Artif Organs. 2017; 40: 67-73
- Long-term heart transplant outcomes after lowering fixed pulmonary hypertension using left ventricular assist devices.Eur J Cardiothorac Surg. 2018; 54: 1116-1121
- Pulmonary artery pressure-guided heart failure management reduces 30-day readmissions.Circ Heart Fail. 2016; 9e002600
- Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction.Circ Heart Fail. 2014; 7: 935-944
- Group 2 PH: medical therapy.Prog Cardiovasc Dis. 2016; 59: 71-77
- Aiming at the appropriate target for the treatment of pulmonary hypertension due to left heart disease.Eur Heart J. 2018; 39: 1265-1268
- Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: a long-term cardiopulmonary exercise testing placebo-controlled study.Eur J Heart Fail. 2012; 14: 82-90
- Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials.BMC Cardiovasc Disord. 2017; 17: 150
- Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial.Eur Heart J. 2015; 36: 2565-2573
- Additional use of a phosphodiesterase 5 inhibitor in patients with pulmonary hypertension secondary to chronic systolic heart failure: a meta-analysis.Eur J Heart Fail. 2014; 16: 444-453
- World Health Organization pulmonary hypertension group 2: pulmonary hypertension due to left heart disease in the adult--a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation.J Heart Lung Transplant. 2012; 31: 913-933
- Effects of sildenafil on prognosis in patients with pulmonary hypertension after left-sided valvular surgery.Heart Lung Circ. 2014; 23: 680-685
- Systematic review of phosphodiesterase-5 inhibitor use in right ventricular failure following left ventricular assist device implantation.Artif Organs. 2016; 40: 123-128
- PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support.Circ Heart Fail. 2008; 1: 213-219
- Sildenafil in heart transplant candidates with pulmonary hypertension.Arch Cardiovasc Dis. 2015; 108: 375-384
- Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial.Eur Heart J. 2018; 39: 1255-1264
- Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis.Chest. 2006; 129: 746-752
- Prognostic factors in medically treated patients with chronic pulmonary embolism.Chest. 2001; 119: 818-823
- Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism.J Am Coll Cardiol. 2017; 69: 1536-1544
- Interventional and surgical modalities of treatment in pulmonary hypertension.J Am Coll Cardiol. 2009; 54: S67-S77
- Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography.Nucl Med Commun. 2012; 33: 459-463
- Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension.J Nucl Med. 2007; 48: 680-684
- Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: the Toronto experience.Can J Cardiol. 2011; 27: 692-697
- Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.Lancet Respir Med. 2017; 5: 785-794
- Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.Eur Respir Rev. 2017; 26: 160119
- Treatment for patients with chronic thromboembolic pulmonary hypertension: where does balloon pulmonary angioplasty sit in the treatment algorithm?.Can J Cardiol. 2017; 33: 430-432
- Chronic thromboembolic pulmonary hypertension.Eur Respir J. 2019; 53: 1801915
The disclosure information of the authors and reviewers is available from the CCS on their guidelines library at www.ccs.ca.
This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.