Diagnostic findings confirming PAH with SSc
What specific clinical echocardiographic PFT, and biomarker findings suggest PAH in a patient with SSc?
• The best predictor for the development of PAH in scleroderma is declining DLco. The DLco is usually very low (<50% predicted) at the time of diagnosis of SSc-PAH, and this is generally in the absence of significant ILD.
• All scleroderma patients should have a baseline set of complete PFTs including DLco, and these should be repeated yearly in most patients. Restrictive physiology (i.e., reductions in total lung capacity or FVC) is seen with ILD, while disproportionate reductions in the DLco are more commonly seen with PAH. A disproportionate decline in the DLco relative to the FVC, as demonstrated by FVC%/DLco% ratio > 1.6, is a strong predictor of PAH development.
• For those at high risk for ILD progression (e.g., those with a positive anti-Scl-70 or isolated nucleolar-ANA), one may choose to obtain PFTs even more frequently. A 6-minute walk test can identify exercise intolerance and hypoxemia, but it is not useful as a screening tool for SSc-PAH because it is neither specific nor sensitive for PAH.
• Baseline echocardiogram is recommended in all SSc patients and should be repeated yearly in most patients. It is reasonable in lower-risk patients (e.g., DLco >70% and stable longitudinally and/or patients with excellent aerobic exercise capacity without symptoms) to reduce the frequency of echocardiography to every 2 years.
• Features on echocardiography that suggest the presence of PH include: right atrial dilation, right ventricular dilation, right ventricular dysfunction, flattening of the interventricular septum, pericardial effusion, or elevated estimated right ventricular systolic pressure (RVSP). Notably, there are significant limitations to its role as a screening tool for SSc-PAH. Echocardiographic views of the right side of the heart can be limited by technical issues (body habitus, etc.) and up to 15% of patients do not have a visible tricuspid regurgitation jet, thereby not allowing for RVSP estimation.
• Elevated B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-proBNP) are surrogate biomarkers for myocardial disease and are frequently elevated in patients with SSc-PAH. They may be useful as an adjunctive component of SSc-PAH screening, with a caveat that early patients without significant right heart failure will have normal values. Both proteins reflect generalized cardiac dysfunction (including left heart failure) and are not specific for PAH. However, recent data do suggest that among those with SSc-PAH, high-levels of BNP or NT-proBNP are associated with a worse prognosis.
• In addition to the individual tests listed earlier, screening algorithms utilizing several combinations of tests have also been studied in the literature. The DETECT algorithm utilizes a two-step process to identify patients who should be referred for RHC and includes variables such as PFTs, EKG, presence of telangiectasia, ACA, NT-proBNP, serum uric acid, and specific measurements from the echocardiogram. This algorithm, when tested in independent cohorts, missed <5% of RHC-confirmed PAH (>95% sensitivity).
Features associated with the presence of PAH in SSc are outlined in the below table.
Features Associated with the Presence of Pulmonary Hypertension in Systemic SclerosisFrom Fischer A, Bull TM, Steen VD. A practical approach to screening for scleroderma-associated pulmonary arterial hypertension. Arthritis Care Res (Hoboken) . 2012 Mar; 64(3):303-10.
|Symptoms||Recent Onset Exertional Dyspnea|
|Physical examination findings||Evidence of right heart compromise (e.g., lower extremity edema, the murmur of tricuspid regurgitation, jugular venous distension, hepatomegaly, or right ventricular heave)|
|Echocardiographic findings||Right ventricular systolic pressure > 40 mmHg|
Tricuspid regurgitation jet > 2.8 m/s
Right ventricular dilation / hypokinesis
Right atrial dilation
|Pulmonary function test parameters||DLco% < 60% in absence of extensive interstitial lung disease or other cause (e.g., emphysema)|
|Other features||Elevated BNP or NT-proBNP|
Unexplained oxygen desaturation with exercise
BNP, B-type natriuretic peptide; DLco, diffusing capacity for carbon monoxide; FVC, forced vital capacity; NT-proBNP, N-terminal-pro-B-type natriuretic peptide.
Decision Algorithm for Screening and Performing a Right Heart Catheterization in SclerodermaFrom Fischer A, Bull TM, Steen VD. A practical approach to screening for scleroderma-associated pulmonary arterial hypertension. Arthritis Care Res (Hoboken) . 2012 Mar; 64(3):303-10. doi:10.1002/acr.20693.PMID: 22076819 .
|Low Risk||Mild Risk||Moderate Risk||High Risk|
|Dyspnea, or Raynaud’s duration > 8 years, positive anti-centromere or isolated nucleolar-ANA||No||Yes||Yes||Yes|
|DLco (without extensive emphysema or ILD)||>70%||>70%||<70%||<60%|
|RVSP||<35 mmHg||<35 mmHg||>35 mmHg||>40 mmHg|
|Next step||Repeat PFTs annually,|
Repeat echo in 2–3 years
|Repeat PFTs annually,|
Repeat echo annually
|Consider repeat echo in 3–6 months or proceed to RHC||Proceed to RHC|
a The presence of echocardiographic features of right ventricular hypokinesis or dilatation or an increased BNP or NT-proBNP in a dyspneic scleroderma patient should lead to RHC irrespective of the estimated RVSP.ANA, antinuclear antibody; BNP, B-type natriuretic peptide; DLco, diffusing capacity for carbon monoxide; FVC, forced vital capacity; ILD, interstitial lung disease; NT-proBNP, N-terminal-pro-B-type natriuretic peptide; PFT, pulmonary function test; RHC, right heart catheterization; RVSP, right ventricular systolic pressure.