Patients with scleroderma can develop heart failure due to high blood pressure in the lungs (a condition called pulmonary arterial hypertension). It is important to find pulmonary arterial hypertension early, so that it can be treated before heart failure develops. However, the tests that we now use to find the earliest form of this disease in scleroderma patients are not good enough. This study will examine whether tests performed during exercise can improve our ability to find early pulmonary arterial hypertension. The study will also try to identify genes that are responsible for the development of pulmonary arterial hypertension.

Inclusion Criteria:

• 30 years or older;

• diagnosis of limited or diffuse scleroderma (American College of Rheumatology criteria)

• for the "high risk" group, one of the following features:

  • resting transthoracic echocardiogram showing elevated right-sided pressures within previous 3 months [tricuspid regurgitation (TR) jet >2.8 m/s or evidence of right ventricular dysfunction]
  • pulmonary function testing (PFT) showing abnormal diffusing capacity of carbon monoxide (DLCO) not due to significant interstitial lung disease (DLCO<60% predicted or FVC: DLCO ratio >1.4)

Exclusion Criteria:

• Pregnancy
• prior diagnosis of pulmonary hypertension
• treatment with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogues
• previous diagnosis of obstructive lung disease or pulmonary thromboembolic disease
• current smoker
• significant valvular disease
• resting echocardiogram showing left ventricular ejection fraction<50% within previous 3 months
• resting echocardiogram showing significant (greater than Grade I) diastolic dysfunction
• pulmonary emboli (past or present).

Volunteers will be recruited from scleroderma clinics, pulmonary hypertension clinics, and (for healthy volunteers) the Ann Arbor area.