Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era.

RATIONALE: Pulmonary arterial hypertension in association with connective tissue disease (CTD-PAH) has historically had a poor prognosis, with a 1-year survival rate among patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) of 45%. However, more therapies have become available. OBJECTIVES: To investigate the survival and characteristics of all patients diagnosed with CTD-PAH in the U.K. pulmonary hypertension service. METHODS: National registry of all incident cases of CTD-PAH diagnosed consecutively between January 2001 and June 2006. MEASUREMENTS AND MAIN RESULTS: Patients with CTD-PAH (429; 73% SSc-PAH) were diagnosed by a catheter-based approach. One- and 3-year survival rates were 78 and 47% for patients with isolated SSc-PAH. Survival was worse for those with respiratory disease-associated SSc-PAH (3-yr survival, 28%; P = 0.005) whereas survival among patients with exercise-induced SSc-PAH was superior (3-yr survival, 86%; P = < 0.001). Age, sex, mixed venous oxygen saturation, and World Health Organization functional class were independent predictors of survival in isolated SSc-PAH. Nineteen percent of patients with exercise-induced SSc-PAH and 39% of patients with isolated SSc-PAH who were in functional classes I and II had evidence of disease progression. The prevalence of diagnosed SSc-PAH is 2.93 per 1 million. The 3-year survival rate of 75% for those with pulmonary arterial hypertension associated with systemic lupus erythematosus (SLE-PAH) was significantly better than that for patients with SSc-PAH (P = 0.01). CONCLUSIONS: Survival of patients with SSc-PAH in the modern treatment era is better than in historical series. A significant proportion of patients with mild functional impairment or exercise-induced SSc-PAH have evidence of disease progression. Survival of patients with respiratory disease-associated pulmonary hypertension is inferior. SLE-PAH has a better prognosis than SSc-PAH.

Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.

RATIONALE: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed over recent years with the growth of pulmonary endarterectomy surgery and the availability of disease-modifying therapies. OBJECTIVES: To investigate the prognosis of CTEPH in a national setting during recent years. METHODS: All incident cases diagnosed in one of the five pulmonary hypertension centers in the United Kingdom between January 2001 and June 2006 were identified prospectively. Information regarding baseline characteristics, treatment, and follow-up was subsequently collected from hospital records. MEASUREMENTS AND MAIN RESULTS: A total of 469 patients received a diagnosis, of whom 148 (32%) had distal, nonsurgical disease. One- and three-year survival from diagnosis was 82 and 70% for patients with nonsurgical disease and 88 and 76% for those treated surgically (P = 0.023). Initial functional improvement in patients with nonsurgical disease was noted but did not persist at 2 years. Significant functional and hemodynamic improvements were seen in surgically treated patients with an increase in six-minute-walk distance of 105 m (P < 0.001) at 3 months. Five-year survival from surgery in the 35% of patients who survived to 3 months but had persistent pulmonary hypertension was 94%. CONCLUSIONS: The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.

Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension.

AIMS: The aims of this study were to evaluate the diagnostic value and to explore the prognostic value of N-terminal brain natriuretic peptide (N-TproBNP) in patients with systemic sclerosis (SSc) both with and without pulmonary arterial hypertension (PAH). METHODS AND RESULTS: N-TproBNP, six-minute walk distance (SMWD), haemodynamics (at right heart catheterization) or tricuspid gradient (by echocardiography), and survival were assessed in 109 patients with SSc. The study population included 68 individuals with PAH [mean pulmonary artery pressure (PAP) >25 mmHg and pulmonary capillary wedge pressure <15 mmHg] and 41 individuals without PAH. In patients with PAH, the prognostic value of baseline and change in WHO functional class, N-TproBNP levels, and SMWD were compared using Kaplan-Meier survival curves and Cox proportional hazard analysis. The mean duration of follow-up was 10 months (range 1-18 months). One year survival in patients with normal PAP was 100% when compared with 83.5% in those with SSc-PAH (P < 0.05). The patients without PAH had a mean N-TproBNP level of 139 pg/mL (SD 151); those with SSc-PAH had a significantly higher mean N-TproBNP level of 1474 pg/mL (SD 2642) (P = 0.0002). Among patients with PAH for every order of magnitude increase in N-TproBNP level there was a four-fold increased risk of death (P = 0.002 for baseline level and P = 0.006 for follow-up level). Baseline N-TproBNP levels were correlated positively with mean PAP (r = 0.62; P < 0.0001), pulmonary vascular resistance (PVR) (r = 0.81; P < 0.0001), and inversely with SMWD (r = -0.46; P < 0.0001). Among patients with SSc-PAH, 13 patients (19%) were in WHO functional classes II and had mean N-TproBNP levels of 325 pg/mL (SD 388). Fifty-three patients (78%) were in WHO classes III and IV and had significantly higher mean N-TproBNP levels of 1677 pg/mL (SD 2835) (P = 0.02). At an N-TproBNP level of 395 pg/mL, the sensitivity and specificity for predicting the presence of SSc-PAH were 56 and 95% respectively. CONCLUSION: Raised N-TproBNP levels are directly related to the severity of PAH. In screening programs, SSc patients with an N-TproBNP in excess of 395 pg/mL have a very high probability of having pulmonary hypertension. Baseline and serial changes in N-TproBNP levels are highly predictive of survival. A 10-fold increase in N-TproBNP level on therapy is associated with a greater than three-fold increase in mortality, and may indicate therapeutic failure.