Pulmonary Hypertension in Systemic Sclerosis: Bridging Pragmatism and Precision

In the recent article by Jacob et al. on the clinical and echocardiographic profile of pulmonary hypertension (PH) in systemic sclerosis (SSc), the authors have attempted to address a clinically significant problem, especially in a resource-limited setting where real-world data is lacking. ¹

PH remains one of the leading causes of mortality in SSc, with a prevalence of 6.3% and 7.7% in the diffuse subtype and limited subtype, respectively. ² The delay in diagnosis, as seen in this study of up to 8 years, is particularly striking and further emphasises the need for routine screening for PH. The current ESC/ERS 2022 guidelines recommend annual screening in all SSc patients, including echocardiography, diffusion capacity (DLCO), biomarkers such as NT-proBNP, with validated algorithms such as DETECT or ASIG guiding referral for right heart catheterisation (RHC). They recommend using the DETECT algorithm in SSc patients of more than 3 years duration with a FVC ≥ 40% and DLCO < 60% to detect asymptomatic PH (Figure 1). ³

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Figure 1.

DETECT Algorithm for Asymptomatic PH.

In this light, while the authors highlight the utility and practicality of transthoracic echocardiography (TTE) especially in India, exclusive reliance on this modality often leads to underestimation or overestimation of the prevalence of PH. TTE should fundamentally be used as a screening tool. The absence of RHC as a comparator in this study limits its ability to precisely classify PH, especially in differentiating WHO Group 1 from Group 3, which further guides treatment choices.

The study appropriately uses key echocardiographic parameters such as tricuspid regurgitant velocity, pulmonary acceleration time, right atrial and ventricle dimensions and TAPSE, however a more comprehensive evaluation including right ventricular longitudinal strain, TAPSE/sPAP ratio (marker of RV pulmonary artery coupling), right ventricular fractional area change, inferior vena cava size for right atrial pressure estimation would have improved the sensitivity of the study to detect PH especially in the absence of RHC and helped in prognostic stratification. Also, assessment of the left heart function, especially the diastolic parameters, would have helped exclude Group 2 PH. ³

The inconsistent availability of simple screening tests such as DLCO and 6-minute walk test limits the utilisation of validated algorithms such as DETECT, which are specifically designed for asymptomatic PH. Their inclusion could have enhanced the study’s relevance to current screening practices. Absence of inexpensive biomarkers such as NT-proBNP is another limitation, which can not only aid in diagnosis but is valuable for treatment response and follow-up.

Few other limitations include a retrospective study design, relatively small sample size and variable follow-up durations. Also, inter-observer variability is not addressed, which becomes especially important during serial monitoring and measuring response to treatment.

Despite these limitations, the study still provides valuable insights into the pragmatic use of TTE in diagnosis and follow-up of SSc patients. Moving forward, prospective studies incorporating a multi-modality approach including imaging, biomarkers and functional tests would significantly enhance the robustness of such data and its reliability to guide treatment options. In summary, this is a relevant study, especially from a resource-limited setting, but a more comprehensive and guideline-aligned approach would further strengthen its applicability.

The treatment of PH in SSc is challenging as it might not have a good response to immunosuppression, being driven by a vasculopathic process. Several drugs have been tried and approved for use in PH. The recent EULAR guidelines (2023) ⁴ recommend initiating dual drug therapy with a phosphodiesterase 5 inhibitor (PDE-5i) and an endothelin receptor antagonist following encouraging results of the AMBITION trial and the post hoc analysis thereafter.^5,6 For severe PAH (WHO Class 3 and 4), intravenous epoprostenol is recommended. Second-line treatment options include the addition of Selexipag or Riociguat. However, the addition of Riociguat to PDE-5i is contraindicated, keeping in mind the risk/benefit ratio as per the PATENT PLUS trial. ⁷ The use of anticoagulation is associated with higher mortality and therefore should be avoided.