Pulmonary hypertension in systemic sclerosis

Etiopathogenesis

The etiology of PAH in SSc is likely to be complex and multifactorial. Major pathologic and histologic (Fig. 1) similarities exist between SSc-associated PAH and primary PAH, but there are some differences. The nature of the initial lesion is unclear, but a plausible sequence of events involves a predisposed individual, including genetic predispositions that are likely to result from a balance between protective or predisposing alleles at several loci that interact, either at the level of gene

Clinical aspects

The heterogenous nature of pulmonary hypertension is illustrated by the current classification of disorders that lead to pulmonary hypertension (Box 1). These conditions are differential diagnoses for PAH complicating SSc. PAH in SSc probably was underdiagnosed in the past. Clinical features likely occur relatively late in the natural history. The earliest symptom is probably exertional breathlessness or reduced exercise capacity. Symptomatically, this may lead to dyspnea on exertion; commonly

Right heart catheterization

Right heart catheterization (RHC) is the gold standard for investigation of PAH in all contexts, although significant thromboembolic disease should be excluded by V/Q scan or CT-pulmonary angiogram. Recurrent pulmonary embolism might be an indication for a filter to be inserted or other specific interventions, including embolectomy.

The advantages of RHC include the direct measurement of PAP, determination of mean PAP which is used for defining true PAH, and the ability to perform a stress test

Prevalence

There is a wide range in the reported frequency of PAH in SSc. This probably results from differences in diagnostic criteria and patient populations that were examined. The best data comes form cardiac catheter studies, although this may underdiagnose because most patients must raise clinical suspicion of PAH to proceed to this invasive test. Our own data suggest a prevalence of 12% to 15% in a hospital-based cohort. This is within the published range of 5% to 50% of SSc cases.

The relationship

Survival

PAH in SSc has a major impact on survival and outcome. A pivotal study by Koh et al [27] examined a small number of cases but determined a median survival of 50% at 12 months if PAH was present. PAH diagnosis was based upon echocardiography. A study from our own unit suggested differences in survival according to the level of PAH by echo-Doppler at diagnosis. For patients with peak above 30 mm Hg at diagnosis, mortality was 20% at 20 months [28]. These simple studies probably overlooked the

Differential diagnosis and classification

There are now well-established diagnostic criteria for PAH. Clinical features and simple investigations, such as ECG, Doppler-echocardiogram, and pulmonary function tests are useful and also assist with important differential diagnoses, such as cardiac involvement or interstitial lung fibrosis. Other causes for pulmonary hypertension (PHT) must be excluded and V/Q scans or computerized tomographic pulmonary arteriogram (CTPA) are important. Additional cardiac tests might be needed to exclude

Monitoring

Monitoring of all patients who have SSc at least by annual Doppler-echocardiogram and pulmonary function testing is not accepted as the standard of practice in Europe and North America. After the diagnosis has been made it is important that the severity of pulmonary hypertension is serially assessed; this is probably most practically done by serial Doppler-echocardiography every 3 to 6 months, depending upon clinical change and also by symptom severity and exercise capacity. The 6-minute walk

Treatment of PAH

The development of treatments of proven efficacy for PAH is a major medical advance and a milestone for SSc management. Along with ACE inhibitors for systemic SRC, effective therapy for PAH represents a major advance in treating a fatal complication of the disease. The history of this progress is fascinating. Historically, pulmonary hypertension therapies were confined to treatment with vasodilators, including calcium channel blockers, which were modestly effective in some patients. Oxygen was

Current management

With established therapies and formalized assessment protocols, there is now an accepted standard of practice for SSc-associated PAH. This is summarized in the algorithm shown in Fig. 2. These care pathways are likely to be refined and modified, but it is a tremendous advance upon the available approaches of just a few years ago. A major goal is the education of patients and the medical community and integration of care between pulmonologists, cardiologists, and rheumatologists. Specialized