Sarcoid-Associated Pulmonary Hypertension and Lung Transplant
Sarcoid-Associated Pulmonary Hypertension and Lung Transplant
The diagnosis of PH in sarcoidosis is challenging because the symptoms of SAPH are nonspecific. One study found no difference in the presenting symptoms of dyspnea, cough, palpitations, and chest pain between sarcoid patients with and without PH. Similarly, signs of right heart failure such as elevated jugular venous pressure, S3 or S4 heart sounds, lower extremity edema, or right ventricular (RV) heave generally occur in late disease and are not sensitive predictors of PH. As discussed earlier, lung function parameters such as decreased FVC, TLC, DLCO, 6 MWT oxygen saturation, or distance may be helpful but do not reliably predict SAPH.
RHC remains the gold standard for diagnosing PH (idiopathic or secondary), as it provides the most reliable measurements of pulmonary hemodynamics and cardiac function. However, RHC is relatively invasive and expensive which precludes its "routine" use in clinical practice. Imaging studies are poor predictors of PH in fibrotic lung diseases including sarcoidosis. Standard radiography and high-resolution computed tomographic (HRCT) scans of the chest may show enlarged pulmonary arteries with right atrial and RV enlargement (Figure 2). However, these findings, particularly dilated pulmonary arteries, often occur in sarcoid patients without PH. A recent retrospective study from a tertiary care center found no difference in pulmonary artery dilation or RV diameter among sarcoid patients with (n = 36) and without (n = 91) PH on HRCT. Although most patients with SAPH have advanced fibrocystic disease (radiographic stage IV) (Figure 3), parenchymal destruction is not necessary for PH development and does not correlate with PH severity. A retrospective evaluation of 22 sarcoid patients with PH (i.e., mPAP > 25 mm Hg on RHC) found that 32% had no fibrosis on chest radiography at the time of PH diagnosis. Another prospective evaluation of 246 sarcoidosis patients found that CT chest scans were similar in patients with and without PH (i.e., systolic pulmonary artery pressure [sPAP] > 40 mm Hg on TTE), with respect to lymph node enlargement, lung opacification, and thickening of bronchovascular bundles.
(Enlarge Image)
Figure 2.
(A–C) A 44-year-old female with biopsy-proven sarcoidosis and severe pulmonary hypertension with pulmonary artery pressure 85/45 (mean 54) mmHg. Contrast computed tomographic images of the chest show pulmonary artery enlargement at 42 mm in maximal axial diameter, severe right atrial and right ventricular enlargement with right ventricular hypertrophy. (D) Diastolic apical four-chamber view on transthoracic echocardiography showing severe right atrial and ventricular enlargement with bowing of the interatrial septum to the left.
(Enlarge Image)
Figure 3.
(A–D) High-resolution computed tomography of the chest in the same patient shows diffuse upper greater than lower lobe peribronchovascular fine and course reticulation, architectural and pleural parenchymal distortion, traction bronchiectasis and bronchiolectasis, and course diffuse ground glass opacification with lobular air trapping.
TTE is noninvasive and currently the screening test of choice for PH of all etiologies. However, TTE has important limitations in patients with interstitial lung disease (ILD). In a study of 106 patients with advanced ILD referred for LT, TTE estimates of sPAP were possible in only 54% of patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TTE for PH (defined as sPAP > 45 mm Hg by RHC) were poor at 85, 17, 60, and 44%, respectively. Similarly, TTE-derived RV abnormalities (e.g., RV dilatation, hypertrophy, or systolic dysfunction) had a sensitivity, specificity, PPV, and NPV for PH of 76, 53, 57, and 74%, respectively. In another study of 61 patients with idiopathic pulmonary fibrosis (IPF), estimates of RVSP were possible in only 33 patients (54%) and the sensitivity, specificity, PPV, and NPV for PH (defined as RSVP > 40 mm Hg by RHC) were 76, 38, 56, and 60%, respectively. TTE estimates of sPAP can over- or underestimate the true RVSP and may be unreliable when used in isolation. Nonetheless, TTE remains the screening test of choice for PH and compliments RHC, as it provides additional data on the structure and function of the right and left heart.
As discussed earlier, several studies have reported associations between PH and physiologic parameters in patients with sarcoidosis, but the results have not been consistent. Parameters that have correlated with PH in sarcoidosis patients include need for supplemental oxygen; decreased 6 MWD; desaturation during 6 MWT; and reduced % DLCO. Importantly, some studies demonstrated a correlation between % FVC and % FEV1, and PH, while other studies did not find an association. These studies demonstrate the limited predictive value of any single parameter to accurately predict PH in sarcoidosis.
Diagnosis of Pulmonary Hypertension in Sarcoidosis
The diagnosis of PH in sarcoidosis is challenging because the symptoms of SAPH are nonspecific. One study found no difference in the presenting symptoms of dyspnea, cough, palpitations, and chest pain between sarcoid patients with and without PH. Similarly, signs of right heart failure such as elevated jugular venous pressure, S3 or S4 heart sounds, lower extremity edema, or right ventricular (RV) heave generally occur in late disease and are not sensitive predictors of PH. As discussed earlier, lung function parameters such as decreased FVC, TLC, DLCO, 6 MWT oxygen saturation, or distance may be helpful but do not reliably predict SAPH.
RHC remains the gold standard for diagnosing PH (idiopathic or secondary), as it provides the most reliable measurements of pulmonary hemodynamics and cardiac function. However, RHC is relatively invasive and expensive which precludes its "routine" use in clinical practice. Imaging studies are poor predictors of PH in fibrotic lung diseases including sarcoidosis. Standard radiography and high-resolution computed tomographic (HRCT) scans of the chest may show enlarged pulmonary arteries with right atrial and RV enlargement (Figure 2). However, these findings, particularly dilated pulmonary arteries, often occur in sarcoid patients without PH. A recent retrospective study from a tertiary care center found no difference in pulmonary artery dilation or RV diameter among sarcoid patients with (n = 36) and without (n = 91) PH on HRCT. Although most patients with SAPH have advanced fibrocystic disease (radiographic stage IV) (Figure 3), parenchymal destruction is not necessary for PH development and does not correlate with PH severity. A retrospective evaluation of 22 sarcoid patients with PH (i.e., mPAP > 25 mm Hg on RHC) found that 32% had no fibrosis on chest radiography at the time of PH diagnosis. Another prospective evaluation of 246 sarcoidosis patients found that CT chest scans were similar in patients with and without PH (i.e., systolic pulmonary artery pressure [sPAP] > 40 mm Hg on TTE), with respect to lymph node enlargement, lung opacification, and thickening of bronchovascular bundles.
(Enlarge Image)
Figure 2.
(A–C) A 44-year-old female with biopsy-proven sarcoidosis and severe pulmonary hypertension with pulmonary artery pressure 85/45 (mean 54) mmHg. Contrast computed tomographic images of the chest show pulmonary artery enlargement at 42 mm in maximal axial diameter, severe right atrial and right ventricular enlargement with right ventricular hypertrophy. (D) Diastolic apical four-chamber view on transthoracic echocardiography showing severe right atrial and ventricular enlargement with bowing of the interatrial septum to the left.
(Enlarge Image)
Figure 3.
(A–D) High-resolution computed tomography of the chest in the same patient shows diffuse upper greater than lower lobe peribronchovascular fine and course reticulation, architectural and pleural parenchymal distortion, traction bronchiectasis and bronchiolectasis, and course diffuse ground glass opacification with lobular air trapping.
TTE is noninvasive and currently the screening test of choice for PH of all etiologies. However, TTE has important limitations in patients with interstitial lung disease (ILD). In a study of 106 patients with advanced ILD referred for LT, TTE estimates of sPAP were possible in only 54% of patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TTE for PH (defined as sPAP > 45 mm Hg by RHC) were poor at 85, 17, 60, and 44%, respectively. Similarly, TTE-derived RV abnormalities (e.g., RV dilatation, hypertrophy, or systolic dysfunction) had a sensitivity, specificity, PPV, and NPV for PH of 76, 53, 57, and 74%, respectively. In another study of 61 patients with idiopathic pulmonary fibrosis (IPF), estimates of RVSP were possible in only 33 patients (54%) and the sensitivity, specificity, PPV, and NPV for PH (defined as RSVP > 40 mm Hg by RHC) were 76, 38, 56, and 60%, respectively. TTE estimates of sPAP can over- or underestimate the true RVSP and may be unreliable when used in isolation. Nonetheless, TTE remains the screening test of choice for PH and compliments RHC, as it provides additional data on the structure and function of the right and left heart.
As discussed earlier, several studies have reported associations between PH and physiologic parameters in patients with sarcoidosis, but the results have not been consistent. Parameters that have correlated with PH in sarcoidosis patients include need for supplemental oxygen; decreased 6 MWD; desaturation during 6 MWT; and reduced % DLCO. Importantly, some studies demonstrated a correlation between % FVC and % FEV1, and PH, while other studies did not find an association. These studies demonstrate the limited predictive value of any single parameter to accurately predict PH in sarcoidosis.