Table 1.
Definition of the comorbidities and confounders
| Lung disease was defined as an abnormality identified on lung function and/or imaging of the lungs and/or a multidisciplinary team (MDT) diagnosis of lung disease. |
| (i) A reduced FEV1/FVC ratio <.7, FEV1 < 60% predicted was considered obstructive lung disease.18,19 |
| (ii) A FEV1/FVC ratio >.7 and reduced FVC <70% was considered restrictive disease18,19 based on trial data specific to pulmonary hypertension. |
| (iii) A TLCO <45% in non-scleroderma population and <32% for the scleroderma population was considered as evidence of lung disease where a diagnosis of pulmonary veno-occlusive disease was not made. |
| Left heart disease was defined by recognized standards on echocardiography suggestive of left heart disease; diastolic dysfunction, systolic dysfunction, left ventricular hypertrophy, and significant valvular heart disease. |
| (i) A high probability of diastolic dysfunction was defined by enlarged left atrial size and mitral Doppler measurements suggestive of diastolic dysfunction (E/e′ ≥ 14, E/A ratio >2). Intermediate probability of diastolic dysfunction was defined as E/e′ > 14 and E/A > 2 on mitral Doppler measurements and no left atrial dilatation.20 |
| (ii) Systolic dysfunction was defined as a either LVEF <45%, (preferentially by biplane echocardiography), or if by visual estimation, moderate to severe LV systolic dysfunction. |
| (iii) Significant left ventricular hypertrophy was defined significant increase in wall thickness (IVSD >1.5 cm). |
| (iv) Significant valvular disease was based on echo parameters, more than moderate left-sided valvular stenosis, regurgitation, or clinical multidisciplinary decision. |
| (v) Where echo data were not available, MDT decision outcomes were used or if patients had ≥3 clinical cardiovascular risk factors; atrial fibrillation, arterial hypertension, diabetes, body mass index ≥30 kg/m2, and/or known coronary artery disease.21,22 |
| Connective tissue disease was defined by clinical diagnosis by American College of Rheumatology criteria and/or auto-immune profile.23 |
FEV1, forced expiratory volume in one second; FVC, forced vital capacity; LVEF, left ventricular ejection fraction; TLCO, transfer factor for carbon monoxide.