Figures
- Figure 1.
Patients in World Health Organization functional class III/IV in various registries. REVEAL: Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management; REVEAL FCC: REVEAL French Comparison Cohort; NIH: National Institutes of Health; PHC: Pulmonary Hypertension Connection; FrR: French registry. REVEAL NIH: REVEAL NIH comparison cohort. Reproduced from [7] with permission from the publisher.
- Figure 2.
Diagnostic algorithm. PH: pulmonary hypertension; ECG: electrocardiogram; PFT: pulmonary function tests; HRCT: high-resolution computed tomography; V′/Q′: ventilation/perfusion; CTEPH: chronic thromboembolic PH; PVOD: pulmonary veno-occlusive disease; RHC: right heart catheterisation; PAH: pulmonary arterial hypertension. Reproduced from [2] with permission from the publisher.
- Figure 3.
Schematic diagram showing the ideal approach to pulmonary arterial hypertension management, which involves regular monitoring and early intervention. Reproduced from [26] with permission from the publisher.
Tables
- Table 1. Clinical classification of pulmonary hypertension (PH)
Classification Sub-classification 1. Pulmonary arterial hypertension 1.1 Idiopathic
1.2 Heritable
1.3 Drugs and toxins induced
1.4 Associated with (APAH)
1.4.1 Connective tissue diseases
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1.4.6 Chronic haemolytic anaemia
1.5 Persistent PH of the newborn1′. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis 2. PH due to left heart disease 2.1 Systolic dysfunction
2.2 Diastolic dysfunction
2.3 Valvular disease3. PH due to lung diseases and/or hypoxaemia 3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental abnormalities4. Chronic thromboembolic PH 5. PH with unclear and/or multifactorial mechanisms 5.1 Haematological disorders: myeloproliferative disorders and splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans’ cell histiocytosis, lymphangioleiomyomatosis neurofibromatosis and vasculitis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease and thyroid disorders
5.4 Others: tumoural obstruction, fibrosing mediastinitis and chronic renal failure on dialysisReproduced from [2] with permission from the publisher.
- Table 2. Patient’s age at diagnosis or during treatment in registry studies
Registry Year Subjects Age yrs NIH [7] 1985 187 36.4±1.1; age at diagnosis REVEAL# [7] 2011 1072 44.9±0.6; age at diagnosis French registry [9] 2006 674 50±15; age at diagnosis REVEAL [10] 2010 2525 50.1±14.4; age at diagnosis UK National Audit¶ [22] 2011 3163 55.3; age of cohort Data are presented as n, mean±sd or mean. REVEAL: Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management. #: REVEAL patients matched to National Institute of Health (NIH) registry patients; ¶: patients being treated with pulmonary arterial hypertension-specific therapies.
- Table 3. Variables with established importance for assessing disease severity, stability and prognosis in pulmonary arterial hypertension
Determinants of prognosis Better prognosis Worse prognosis Clinical evidence of RVF No Yes Rate of progression of symptoms Slow Rapid Syncope No Yes WHO-FC I, II IV 6MWT Longer (>500 m) Shorter (<300 m) Cardiopulmonary exercise testing Peak O2 consumption >15 mL·min−1·kg−1 Peak O2 consumption <12 mL·min−1·kg−1 BNP/NT-proBNP plasma levels Normal or near normal Very elevated and rising Echocardiographic findings No pericardial effusion Pericardial effusion TAPSE >2.0 cm TAPSE <1.5 cm Haemodynamics Pra <8 mmHg and CI ≥2.5 L·min−1·m−2 Pra >15 mmHg or CI ≤2.0 L·min−1·m−2 RVF: right ventricle failure; WHO-FC: World Health Organization functional class; 6MWT: 6-min walk test; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; TAPSE: tricuspid annular plane systolic excursion; Pra: right atrial pressure; CI: cardiac index. Reproduced from [2] with permission from the publisher.
- Table 4. Clinical trials of combination therapy in pulmonary arterial hypertension (PAH)
Trial [ref.] Background therapy/study drug Design Patients Subjects n Duration weeks Primary end-point Efficacy Primary end-point TTCW BREATHE-2 [30] Epoprostenol/bosentan Upfront RCT IPAH, SSc, SLE 33 16 TPR - ND STEP [31] Bosentan/iloprost (inhaled) Sequential RCT PAH 67 12 6MWD - + COMBI [32] Bosentan/iloprost (inhaled) Sequential open label IPAH 40 12 6MWD - - PACES [33] Epoprostenol/sildenafil Sequential RCT IPAH, CTD, CHD 277 12 6MWD + + TRIUMPH-1 [34] Sildenafil, bosentan or both/treprostinil (inhaled) Sequential RCT PAH 235 12 6MWD + - FREEDOM-C [35] Sildenafil, ERA or both/treprostinil (oral) Sequential RCT PAH 354 16 6MWD - - IMPRES [36] ≥2 PAH-specific therapies/imatinib Sequential RCT IPAH, HPAH, CTD, CHD 202 24 6MWD + - PHIRST [37] Bosentan/tadalafil Sequential RCT PAH 216# 16 6MWD - ND EARLY [23] Sildenafil/bosentan Sequential RCT PAH 28¶ 24 PVR + ND TTCW: time to clinical worsening; ERA: endothelin receptor antagonist; RCT: randomised controlled trial; IPAH: idiopathic PAH; SSc: systemic sclerosis; SLE: systemic lupus erythematosis; CTD: connective tissue disease; CHD: congenital heart disease; HPAH: heritable PAH; TPR: total pulmonary resistance; 6MWD: 6-min walk distance; PVR: pulmonary vascular resistance; ND: not determined; +: met end-point; -: did not meet end-point. #: only patients included in the subgroup analysis of patients who were receiving concomitant bosentan at baseline were included; ¶: only patients included in the subgroup analysis of patients who were receiving concomitant sildenafil at baseline were included.
