How to detect disease progression in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rapidly progressive disease, ultimately leading to right heart failure and death. Accumulating evidence indicates that intervention early in disease progression results in better outcomes than delaying treatment. In this review we will discuss the assessments and strategies that can be used to monitor disease progression and guide clinical management. Many tools, such as symptoms, functional classification, exercise capacity, haemodynamic measures, findings on cardiac imaging and levels of biomarkers, have shown to be prognostic for survival both at diagnosis and during treatment. However, attempts to define goal thresholds have produced a variety of results. Several groups have developed risk calculators to estimate individual patients' mortality risk, but the accuracy of these tools across different patient populations remains unknown. What is clear is the importance of regularly assessing a range of parameters and then tailoring treatment goals to each patient. In addition, the use of a multidisciplinary team approach is crucial in order to support patients through all aspects of managing their condition. There is still an urgent need for prospective collaborative initiatives to assess novel goals and improve treatment strategies that would allow physicians to personalise and optimise clinical management for their patients with PAH.

Pulmonary artery pressure limits exercise capacity at high altitude.

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day(-1) for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V'(O(2),max), by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V'(O(2),max) were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.

Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9 +/- 4 versus 11.7 +/- 2.3 cm.s(-1)) and the isovolumic relaxation time corrected to RR interval was increased (6.5 +/- 2.9 versus 4.5 +/- 2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.