Figures
- FIGURE 1
The reported incidence of SAPH from various centres across the world. The city or country of origin of the study is indicated. A higher incidence of SAPH was found for patients being evaluated for persistent dyspnoea or lung transplantation [3–16]. SAPH: sarcoidosis-associated pulmonary hypertension; UNOS: United Network Organ Sharing.
- FIGURE 2
The 1-, 3- and 5-year survival from sarcoidosis-associated pulmonary hypertension [7, 13, 21, 23, 24]. #: For three of the studies [7, 13, 23], the survival was estimated based on the Kaplan–Meier survival curves presented in the papers.
- FIGURE 3
Algorithm for who should undergo transthoracic echocardiogram to evaluate for SAPH. 6MWD: 6-min walk distance; BNP: B-type natriuretic peptide; BSA: body surface area; CT: computed tomography; DLCO: diffusing capacity of the lung for carbon monoxide; ECG: electrocardiogram; FVC: forced vital capacity; MRI: magnetic resonance imaging; NT-proBNP: N-terminal (NT)-pro hormone BNP; NYHA-FC: New York Heart Association functional class; PFT: pulmonary function test; PH: pulmonary hypertension; RV: right ventricle; SAPH: sarcoidosis-associated pulmonary hypertension. #: Transthoracic echocardiogram recommended to assess for SAPH and left ventricular dysfunction. ¶: May be more accurate if corrected for BSA.
- FIGURE 4
Probability of pulmonary hypertension from echocardiography findings of direct estimate of right ventricular systolic pressure and indirect evidence of right ventricular strain. Reproduced from Galie et al. [51]. PA: pulmonary artery; PH: pulmonary hypertension.
- FIGURE 5
Algorithm for who should undergo RHC based on echocardiography. FVC: forced vital capacity; RHC: right-heart catheterisation.
- FIGURE 6
Interpretation of right-heart catheterisation and subsequent treatment recommendations are made in the figure. mPAP: mean pulmonary artery pressure; PAWP: pulmonary artery wedge pressure; PH: pulmonary hypertension; PVR: pulmonary vascular resistance; WHO: World Health Organization; WU: Wood's unit. #: Cardiac sarcoidosis may be evident in pre-capillary PH without changing haemodynamics. ¶: Careful evaluation should be performed by a cardiologist/PH specialist to distinguish PH due to left heart disease with subsequent pre-capillary vascular changes and sarcoidosis-associated PH.
- FIGURE 7
Proposed algorithm for treating pre-capillary sarcoidosis-associated pulmonary hypertension. FVC: forced vital capacity; PDE-5: phosphodiesterase 5.
Tables
- TABLE 1
Summary of Task Force comments.
1. Presence of SAPH is associated with significant symptomatology and morbidity, as evidenced by increased WHO FC, decreased 6MWD or desaturation and increased oxygen use.
2. Pulmonary hypertension is an independent predictor of mortality in patients with sarcoidosis.
3. Since the cause of SAPH is multifactorial, the committee commented that the current recommendation to keep SAPH in Group 5 was reasonable. The committee considered that patients with left ventricular disease either due to sarcoidosis or other conditions should be treated as WHO Group 2. The committee felt it was important to identify a dominant cause for SAPH on an individual basis, as it is likely to have treatment implications.
4. The suggestions of who should undergo transthoracic echocardiogram are summarised in figure 3.
5. The committee's suggestions regarding who should undergo RHC are summarised in figure 5.
6. The committee suggested that the right-heart catheterisation results should be interpreted by a multidisciplinary team with at least a sarcoidosis and PH expert and decisions should be made as summarised in figure 6.
7. Evaluate for pulmonary artery stenosis or mediastinal compression by chest imaging.
8. In SAPH, treatment decision and follow-up should be made by a multidisciplinary team with a sarcoidosis and a PH expert. Off-label use of PAH medical therapy may be considered for symptomatic patients on a case-by-case basis (figure 7).
9. Patients who have failed to respond to treatment for PH should be referred for lung transplant evaluation, if they are deemed otherwise to be appropriate candidates.
SAPH: sarcoidosis-associated pulmonary hypertension; WHO FC: World Health Organization Functional Class; 6MWD: 6-min walk distance; RHC: right-heart catheterisation; PH: pulmonary hypertension; PAH: pulmonary arterial hypertension.
- TABLE 2
Causes of pulmonary hypertension in sarcoidosis patients
Condition Potential treatments Vascular disease Vasculitis Glucocorticoids and other anti-inflammatory treatments
Pulmonary vasodilatorsGranulomatous vascular involvement Glucocorticoids and other anti-inflammatory treatments
Pulmonary vasodilatorsVeno-occlusive disease Glucocorticoids and other anti-inflammatory treatments
Careful use of pulmonary vasodilatorsPulmonary embolism (CTEPH) Anticoagulation
Balloon pulmonary angioplasty
Pulmonary endarterectomy
Pulmonary vasodilatorsInterstitial lung disease Parenchymal lung disease due to granulomas Glucocorticoids and other anti-inflammatory treatments Parenchymal lung disease due to fibrosis Anti-fibrotic agents Hilar and mediastinal distortion Pulmonary artery/vein extrinsic compression Glucocorticoids and other anti-inflammatory treatments
Dilation and/or stenting of compressed vesselsFibrosing mediastinitis Dilation and/or stenting of compressed vessels Extrapulmonary disease Left ventricular systolic dysfunction Glucocorticoids and other anti-inflammatory treatments
Diuretics, afterload reductionLeft ventricular diastolic dysfunction Diuretics Sleep apnoea CPAP, oxygen and other measures Liver disease Glucocorticoids and other anti-inflammatory treatments CTEPH: chronic thromboembolic pulmonary hypertension; CPAP: continuous positive airway pressure.
- TABLE 3
Treatment of pre-capillary SAPH
Highest level of evidence study in patients with SAPH Total number of patients with SAPH treated Results in sarcoidosis Prostenoids Epoprostenol Retrospective OL positive [78, 79] 12 Haemodynamics improved [78, 79] Iloprost Prospective, OL [72] 15 of 22 enrolled completed 16 weeks’ therapy In sarcoidosis, haemodynamics and QoL improved [72] Endothelin receptor antagonists Bosentan DBPC [71] 23 Haemodynamics improved, no change in 6MWD [71] Ambrisentan Prospective OL [73] 21 Nonsignificant improved QoL, no change 6MWD [73] Macitentan Retrospective OL [82] 6 WHO FC improved in 4/6 treated patients [82] Phosphodiesterase 5 inhibitors Sildenafil Retrospective OL [16] 12 Haemodynamics improved, 6MWD no changes Tadalafil Prospective OL [74] 12 No significant changes in 6MWD and QoL Others Riociguat DBPC [70] 16 TCW and 6MWD significantly better compared with placebo Combination therapy Retrospective OL positive [8, 21, 77] 29 Haemodynamics and 6MWD improved in some SAPH: sarcoidosis-associated pulmonary hypertension; OL: open-label; QoL: quality of life; DBPC: double-blind, placebo-controlled; 6MWD: 6-min walk distance; WHO FC: World Health Organization functional class; TCW: time to clinical worsening.
- TABLE 4
Noninvasive PH markers
Cardiac functional impairment
Echocardiography
Cardiac magnetic resonance
PH severity evaluation
Echocardiography
Cardiac stress
BNP
Morphologic consequences
PA dilatation on CT
Global functional consequences
6MWD
Oxygen desaturation during 6MWD
Heart rate recovery
Pulmonary function vasculopathy profiles
Severe reduction in DLCO
DLCO reduction that is disproportionate to reductions in lung volumes – KCO, the DLCO/FVC ratio
PH: pulmonary hypertension; BNP: B-type natriuretic peptide; PA: pulmonary artery; CT: computed tomography; 6MWD: 6-min walk distance; DLCO: diffusing capacity of the lung for carbon monoxide; KCO: transfer coefficient of the lung for carbon monoxide; FVC: forced vital capacity.
