Who & When

Screening is most strongly recommended for Systemic Sclerosis (SSc) and Scleroderma-spectrum disorders, particularly when disease duration exceeds 3 years. Other factors prompting screening include those with symptoms, positive biomarkers (e.g., anti-centromere Antibody, U1-RNP), or abnormal Pulmonary Function Tests in other CTDs like SLE, MCTD, and RA.

Timing

• At baseline: Soon after diagnosis of SSc or scleroderma-spectrum disorder.
• Annually: In asymptomatic patients with SSc, especially those with DLCO <60% predicted or FVC/DLCO >1.6.
• Immediately: If new symptoms arise (e.g., dyspnea, syncope, oedema) or biomarker changes suggest increased risk.

Screening modalities

1. Transthoracic echocardiography (TTE / echo)

Echocardiography is the basic screening tool. Echocardiographic markers for PAH in CTDs include Tricuspid Regurgitation Velocity (TRV), Systolic Pulmonary Artery Pressure (sPAP), Tricuspid Annular Plane Systolic Excursion (TAPSE), Right Atrial (RA) area, Right Ventricle (RV) function, and emerging ratios like TAPSE/sPAP and sPAP/PAAT (Pulmonary Artery Acceleration Time). These reflect pulmonary pressures, right ventricular (RV) function, and RV-pulmonary arterial coupling. Elevated TRV (>2.8 m/s), sPAP (>35 mmHg), and low TAPSE/sPAP (<0.55 mm/mmHg) suggest elevated pulmonary pressure. The TAPSE/sPAP ratio closely aligns with findings from invasive right-heart catheterisation.

Although non-invasive and widely available, echocardiography has variable specificity, can underestimate pulmonary pressures, and is operator-dependent. It also has reduced accuracy in early PAH or when the TR jet is not measurable, hence it is used in combination with other tests.

2. Pulmonary function tests (PFTs) with Diffusing Capacity of lungs for Carbon Monoxide (DLCO)

A low DLCO (e.g., <60% predicted) and a disproportionate drop in DLCO relative to lung volumes (e.g., preserved FVC) suggest pulmonary vascular disease. Some algorithms use the FVC / DLCO ratio (e.g.,>1.6) as a red flag.

3. Biomarkers:  N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) or BNP

NT-proBNP has high sensitivity but variable specificity, so it is not sufficient alone. The cutoff ranges between 125–500 pg/mL. 

4. Electrocardiogram (ECG) / chest imaging / other adjuncts

ECG showing right-axis deviation, right ventricular hypertrophy, etc., may support the suspicion. Some algorithms incorporate ECG features in detecting PAH.

5. Screening algorithm (DETECT as exemplar)

The DETECT algorithm (for SSc patients >3 years old with DLCO <60% and FVC ≥40%) integrates 8 variables (from non-echo and echo findings) into a two-step algorithm to reduce missed PAH and unnecessary Right Heart Catheterisation (RHC) referrals.

Step 1 uses non-echocardiographic variables (e.g., DLCO, FVC/DLCO ratio, telangiectasias, NT-proBNP, urate, ECG axis).

If a risk threshold is exceeded, step 2 adds echo parameters (right atrium area, TRV), and if the combined risk exceeds the threshold, referral for RHC is recommended.

This helps improve sensitivity while limiting unnecessary invasive testing.

6. Confirmatory testing

Right Heart Catheterisation is the gold standard for confirming PAH, defining hemodynamics (mean pulmonary artery pressure, pulmonary vascular resistance, wedge pressure), and excluding left-heart or other causes of pulmonary hypertension.

RHC is recommended in cases where noninvasive screening suggests an elevated probability of PAH, or in unexplained symptoms after a noninvasive workup

Early detection via screening is associated with diagnosis at milder stages and possibly better survival compared to symptom-based diagnosis.

False positives (leading to unnecessary RHC), test costs, heterogeneity between CTDs (less robust data in non-SSc), and potential overdiagnosis are the caveats of RHC.

Suggested Reading

1. Dragoi IT, Rezus C, Burlui AM, Bratoiu I, Rezus E. Multimodal Screening for Pulmonary Arterial Hypertension in Systemic Scleroderma: Current Methods and Future Directions. Medicina (Kaunas). 2024;61(1):19.
2. Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):3194-3201.
3. Coghlan JG, Denton CP, Grünig E, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340-1349.
4. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2023;61(1):2200879.