Advances in diagnosis and risk stratification for pulmonary arterial hypertension

Geetha A/P Kandavello
National Heart Institute, Kuala Lumpur, Malaysia

Pulmonary arterial hypertension (PAH) is a complex and progressive vasculopathy associated with significant morbidity and mortality. Advances in early diagnosis and refined risk stratification have markedly improved the ability to tailor management strategies and optimize outcomes. Diagnostic modalities have evolved to include high-resolution imaging, such as cardiac magnetic resonance (CMR), which provides superior assessment of right ventricular function—an essential prognostic marker [1]. Biomarkers like NT-proBNP (>1400 pg/mL) and high-sensitivity troponin continue to offer valuable insights into cardiac stress and disease severity [2].

Genetics and genomics have become increasingly relevant in the diagnostic and prognostic landscape. Pathogenic variants in genes such as BMPR2, EIF2AK4, TBX4, and SOX17 are now identified in up to 80% of heritable PAH and 20% of idiopathic cases [3]. BMPR2 mutations, in particular, are associated with earlier disease onset, more severe hemodynamics, and poorer long-term outcomes [4]. Genetic testing is now recommended in all patients with idiopathic, heritable, or pediatric PAH, not only for risk stratification but also for family screening and potential inclusion in gene-targeted clinical trials [5].

Risk stratification tools such as the REVEAL 2.0 risk calculator and the ESC/ERS 2022 four-strata model integrate clinical, biochemical, and hemodynamic data to predict 1-year mortality and guide therapy [6,7]. For example, a patient with WHO functional class III, 6MWD <165 m, and mean right atrial pressure >14 mmHg falls into the high-risk category, warranting immediate escalation to parenteral prostacyclin-based therapy. Clinical trials including AMBITION [8], SERAPHIN [9], and GRIPHON [10] have demonstrated the benefits of early, risk-adapted combination therapy in improving survival and delaying disease progression.

Emerging technologies, such as implantable pulmonary artery pressure monitors (e.g., CardioMEMS) [11] and remote digital phenotyping [12], are enabling real-time, continuous risk reassessment and more personalized treatment interventions. These advances in diagnostics, genomics, and dynamic risk stratification are reshaping PAH management toward a more precision-based, outcome-driven approach.