PURPOSE:To investigate the association of specific auto-antibodies with pulmonary hypertension (PHTN) in patients with scleroderma (SSc).
METHODS:We have shown that SSc patients whose estimated RVSP increased by >20mmHg on exercise echocardiogram (+EE) had a high likelihood of having PHTN on right heart catheterization (CATH) (Chest, 2008). In this observational study, SSc patients underwent EEs (standard Bruce protocol). Those with a +EE then underwent an exercise CATH. Patients with anti-centromere (ACA), anti-topoisomerase (Scl-70) or nucleolar pattern (NUC) were compared. An abnormal RATIO was defined as FVC% / DLCO% >1.6.
RESULTS:Patients with an abnormal RATIO were more likely to have a +EE, 67% vs 28% (p<0.003). However, +EE did not correlate with resting RVSP. Among +EE patients: Amongst ACA patients, 67% had exercise-induced PHTN, 22% resting PHTN, 1 patient (age 77) diastolic dysfunction (DD) with normal resting PAOP which increased to 25mmHg with exercise. All Scl-70 patients had hypoxia at rest and severe fibrosis. Three had abnormal RATIOs; 3 had mild resting PHTN on CATH (meanPAP 28mmHg) and 1 had DD (prior renal crisis). NUC patients were different. Many had interstitial lung disease, but no hypoxia. Only 47% (6/13) had abnormal RATIOs. Among 8 patients with DD, 6 had increased PAOP only on exercise.
CONCLUSION:Auto-antibodies appear to be strongly associated with the type of PHTN: ACA patients appear to have classic vasculopathy, PAH (Class 1). Scl-70 patients less commonly have +EE. Their PHTN is milder and hypoxia-driven (Class 3). NUC patients have more false positive EEs, because of a high frequency of DD, with pulmonary venous hypertension (Class 2). Apart from the larger LA diameter, these patients did not have obvious DD on echocardiogram.
CLINICAL IMPLICATIONS:Auto-antibodies may potentially be used to predict the type of PHTN in SSc patients. Patients with a ‘normal’ resting RVSP and +EE, may have resting PHTN or exercise-induced PHTN confirmed on CATH. Furthermore, an exercise CATH may be necessary to rule out DD, even if there is no evidence for diastolic dysfunction on echocardiogram.
DISCLOSURE:Tunay Kuru, No Financial Disclosure Information; No Product/Research Disclosure Information