Diagnosis of Pulmonary Arterial Hypertension in a Patient With Systemic Sclerosis

Jörg HW Distler, MD; Marius M Hoeper, MD; Oliver Distler, MD

Disclosures

Nat Clin Pract Rheumatol. 2008;4(3):160-164. 

In This Article

Discussion of Diagnosis

This case highlights the challenges and limitations of diagnosing PAH in individuals with SSc. PAH is not rare in patients with SSc. The estimated prevalence varies widely according to the method used for diagnosis. Prevalence of pulmonary hypertension has been suggested to be as high as 26.7% in patients with SSc or with mixed connective tissue disease in a community rheumatology practice setting, with pulmonary hypertension defined as RVSP ±40 mmHg by TTE.[1] These data, however, must be interpreted with caution because echocardiography has a high rate of false positives, and the diagnosis of PAH requires right heart catheterization. Another study found that 12% of patients with SSc had PAH, as diagnosed by right heart catheterization.[2]

Unfortunately, clinical symptoms of PAH are unspecific and are late manifestations of the disease.[3] As in this case, dyspnea on exertion is often the leading clinical symptom; however, dyspnea indicates that the characteristic vascular remodeling of small and middle sized arteries and arterioles has already developed. In SSc, the differential diagnosis of unspecific signs and symptoms such as dyspnea on exertion, inability to climb stairs, and fatigue is even more challenging when considering other frequent disease manifestations, such as interstitial lung fibrosis and musculoskeletal disorders and deconditioning.

The lack of early clinical symptoms, poor prognosis, rather high prevalence, and availability of effective therapies provide a rationale for the regular screening for PAH in patients with SSc.

PAH can occur in all disease stages of SSc, as well as in all disease subsets. Current recommendations, such as the American College of Chest Physicians guidelines,[4] suggest that patients with SSc but without obvious symptoms of PAH should be screened by TTE to facilitate early detection and intervention. Screening has become even more important given that treatment with endothelin-receptor antagonists might improve survival in patients with PAH associated with SSc.[4,5]

A high clinical awareness and a low threshold for diagnostic tests is recommended for identification of PAH in patients with other connective tissue diseases.[3,6] Certain subgroups of SSc patients, such as patients with limited cutaneous disease and anticentromere antibodies, are at especially high risk of developing PAH, and there is general agreement that these patients need regular monitoring and particular attention.[7] Although PAH can develop in all disease stages and can be the presenting symptom of SSc, it most frequently develops at later stages, years after diagnosis.[8]

Decreasing isolated DLCO is not a specific symptom of PAH;[9] however, a case–control study from the Pittsburgh Scleroderma Database identified decreasing DLCO with normal lung volumes as an excellent predictor of subsequent development of PAH,[10] which was confirmed in other studies. Right heart catheterization to detect asymptomatic PAH could, therefore, have been considered for our patient at presentation, when an isolated DLCO of <60% was observed, even with a normal echocardiography and in the absence of symptoms.

Many of these established and potential risk factors for PAH were present in our patient. It has to be emphasized that the discussed research findings have a direct implication for the daily clinical care of SSc patients: those patients with minimal to mild skin fibrosis—who are often considered to have a benign form of the disease—need special attention and screening for PAH, in particular if additional risk factors are present.

Optimum screening tests need to be fast, noninvasive, readily available, cheap, feasible, and fully validated for the disease parameter they are measuring. Such optimum screening tests do not exist for SSc-associated PAH.[11] TTE is the best available and most often recommended screening test for PAH because it fulfils many of the requirements listed above; its usefulness is limited by the fact that the estimated RVSP often does not correlate well with the results obtained by right heart catheterization, giving TTE an incidence of false positives of up to 40%. If sufficiently high thresholds, such as an estimated RVSP >45 mmHg, are used, however, the specificity of TTE might be acceptable. In one study, PAH was confirmed in 97% of patients with an estimated RVSP >45 mmHg by right heart catheterization,[12] whereas other studies found lower correlations between estimated RVSPs by echocardiography and the findings on right heart catheterization.[13]

TTE is not a good method of excluding a diagnosis of PAH, in particular in patients with mild or early forms; therefore, patients might sometimes have PAH detectable by right heart catheterization despite normal or borderline values on echocardiography.[12] This fact highlights the need for additional screening tests in order to identify early forms of PAH in patients with SSc. Relatively new techniques, such as stress Doppler echocardiography, are promising,[14] but have not yet been validated for routine clinical use. Pro-BNP is a biomarker that correlates well with hemodynamic measures and predicts survival in patients with PAH associated with SSc. The specificity and sensitivity of pro-BNP to predict PAH are similar to those of TTE,[15] and pro-BNP is often used as a follow-up marker in patients with PAH. A diagnosis of left heart disease needs to be excluded. As outlined above, lung function tests including DLCO can give additional hints for the presence of PAH.

In patients with suspected PAH, the diagnosis should be confirmed by direct measurement of pulmonary hemodynamics by the use of right heart catheterization.[16] PAH is defined as a resting mean pulmonary arterial pressure of ±25 mmHg with a normal capillary wedge pressure of ≤15 mmHg, on right heart catheterization.[6] The possibility of elevated pulmonary capillary wedge pressures can only be excluded by right heart catheterization in patients with suspected PAH. Right heart catheterization is, therefore, essential for the correct diagnosis of PAH. Patients with increased pulmonary pressures from other conditions, such as interstitial lung disease or chronic thrombembolic disease, are not classified as cases of PAH. These conditions need to be excluded by procedures such as HRCT and ventilation/perfusion lung scanning.

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