Pulmonary hemodynamics and transplant‐free survival in sarcoidosis‐associated pulmonary hypertension: Results from an international registry

Abstract

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis‐associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant‐free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan−Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was decreased. Decreased transplant‐free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant‐free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut‐offs with decreased transplant‐free survival in the SAPH population. Neither cut‐off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant‐free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease

“…This change in definition results from studies demonstrating that a PVR threshold of 5 WU is a better predictor of mortality in patients with COPD-PH and ILD-PH [ 4 , 6 ]. This finding was also found in patients with sarcoidosis-associated PH [ 5 ]. Severe PH as defined by the 2022 ESC/ERS guidelines was a strong independent predictor of mortality in our cohort of patients, even when accounting for underlying lung disease and lung function.…”

“…Pulmonary hypertension (PH) often accompanies chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis, and other interstitial lung diseases (ILDs) [ 1 ]. The presence of PH in chronic lung disease portends unfavorable outcomes [ 2 , 3 , 4 , 5 , 6 , 7 ]. Notably, hemodynamic parameters may play a more integral role than lung function in long-term outcomes [ 8 ].…”

“…Moreover, elevated pulmonary vascular resistance (PVR) is significantly associated with mortality including lung transplant waitlist mortality in patients with COPD, even when accounting for spirometry [ 4 , 15 ]. Beyond COPD, elevated PVR is also associated with increased mortality in patients with ILD and sarcoidosis [ 5 ]. The diagnosis of IPF, 6 min walk distance (6MWD), and reduced diffusing capacity of the lung for carbon monoxide (DLCO) may prognosticate patients with chronic lung disease and PH [ 3 , 13 , 16 ].…”

Sarcoidosis-Associated Pulmonary Hypertension

“…In the international registry including unselected patients with SAPH, 115/159 (72.3%) received PAH-targeted therapy, which consisted of monotherapy in 88.2% (PDE5-i: n = 86, ERA: n = 56), bitherapy in 17.6% (PDE5i + ERA: n = 28), and tritherapy in 6.3% (PDE5-I + ERA + prostanoid: n = 10) [45]. In both registries, PAH-targeted therapy was not associated with decreased mortality, provided that treated patients had a significantly worse condition at baseline than the untreated ones [41,45,84].…”

“…As far as the definition of severe SAPH goes, with the foreseeable impact of therapeutic measures and timing on LTx evaluation, one study showed that both mPAP ≥ 40 mmHg and PVR ≥ 5 WU were strongly associated with a shorter transplant-free survival and increased risk of death or LTx [84]. Interestingly, and in contrast to common definitions of severe PH in chronic lung diseases, neither a mPAP > 35 mmHg nor mPAP > 25 mmHg with cardiac index ≤ 2 L/min/m 2 were associated with these outcomes.…”