Highlights
- Early detection and personalized treatment strategies are crucial for managing pulmonary hypertension effectively.
- Advances in diagnostic tools and therapies offer hope for improved patient outcomes in PH management.
Summary and Overview
Pulmonary hypertension (PH) is a progressive cardiovascular disorder marked by elevated mean pulmonary arterial pressure above 20 mmHg. Classified by the WHO into five groups based on underlying causes, PH presents diverse clinical challenges and significant morbidity. Advances in 2025 focus on early detection using refined diagnostics, including echocardiography, right heart catheterization, and AI-enhanced assessment. Updated risk tools like the REVEAL score improve prognostication and guide personalized treatments targeting key pathways such as endothelin receptors, prostacyclin analogues, and TGF-β/BMPR2 signaling. Multidisciplinary care and perioperative management for noncardiac surgery patients are emphasized. Despite progress, challenges remain in treatment adherence and psychosocial support, while novel therapies including gene modulation and immunomodulation offer promise for better outcomes.
Pathophysiology and Emerging Therapies
PH results from elevated pulmonary arterial pressure via pre-capillary (PAH), post-capillary (left heart disease), or mixed mechanisms. PAH involves vascular remodeling driven by hyperproliferation and resistance to apoptosis, influenced by genetic factors like BMPR2 mutations. Vascular remodeling also involves inflammatory cells and platelets. Emerging treatments target the BMP/TGF-β and PDGF pathways, with drugs like sotatercept showing clinical benefits. Additional approaches include receptor tyrosine kinase inhibitors, epigenetic modulators, immunotherapies, and novel interventions such as pulmonary artery denervation.
Diagnosis and Classification
Diagnosis combines clinical evaluation, imaging, and hemodynamics, with right heart catheterization as the gold standard. Echocardiography, CT, V/Q scans, and cardiopulmonary exercise testing assist in identifying PH type and severity. AI applications improve diagnostic accuracy. The 2025 classification lowers the mPAP threshold to >20 mmHg and adjusts pulmonary vascular resistance criteria, facilitating earlier detection and treatment. Specialized centers provide ongoing monitoring using multimodal assessments to guide management.
Management Strategies
Updated PH management integrates refined classification, individualized risk assessment, targeted pharmacologic therapies, and multidisciplinary care. Perioperative management includes thorough risk assessment, optimization before surgery, vigilant intraoperative monitoring, and postoperative support, preferably in specialized centers for high-risk patients. Pharmacologic treatments focus on prostacyclin, endothelin, and nitric oxide pathways, with combination therapy recommended for many patients. Novel agents targeting TGF-β/BMPR2 signaling, epigenetic regulators, tyrosine kinase inhibitors, and immunomodulators address vascular remodeling and inflammation. Comprehensive care involves cardiologists, pulmonologists, anesthesiologists, and surgeons to tailor treatments and consider palliative options when necessary.
Monitoring, Adherence, and Patient Support
Effective PH management relies on regular risk stratification using tools like REVEAL 2.0 to monitor disease progression and guide therapy. Follow-up includes clinical evaluation, imaging, functional tests, and biomarkers, with AI enhancing assessment accuracy. Medication adherence is crucial but challenged by psychosocial factors and therapeutic inertia. Strong patient–clinician relationships, education, and multidisciplinary support improve adherence and outcomes. Organizations such as the American Lung Association play key roles in promoting early diagnosis and patient education. Addressing sociodemographic barriers and clinician burnout contributes to better care delivery.
Prognosis and Future Directions
Refined risk assessment models have improved prognostic accuracy in PH. Emerging therapies targeting molecular pathways—such as sotatercept for TGF-β modulation, epigenetic inhibitors, receptor tyrosine kinase blockers, and immunomodulatory agents—show promise in reducing vascular remodeling and improving survival. Investigational metabolic and hormonal treatments may complement existing therapies. Ongoing research is vital to optimize these approaches, validate safety, and tailor treatments to patient subgroups, aiming to transform PH management and outcomes.