Highlights
- Pulmonary hypertension significantly impacts public health, demanding advanced personalized treatment strategies.
- Delayed diagnosis of PH remains a major challenge, emphasizing the need for improved awareness and access.
Summary
Pulmonary hypertension (PH) is a serious cardiovascular disorder with elevated pulmonary artery pressure leading to right heart dysfunction and premature death if untreated. In the U.S., PH is classified into five groups based on causes: pulmonary arterial hypertension (PAH), PH from left heart disease, lung diseases, chronic thromboembolic disease, and multifactorial causes. PAH is rare but severe, with a median survival of seven years. Left heart disease is the most common PH cause in the U.S. Diagnosis relies on clinical evaluation and right heart catheterization, but delays are common due to nonspecific symptoms. Treatments include novel pharmacotherapies and surgical options, with ongoing research toward personalized medicine. Health disparities and variable care access remain challenges.
Classification, Causes, and Epidemiology
PH is classified into five groups: Group 1 (PAH) involves vascular remodeling with high pulmonary resistance; Group 2 results from left heart disease; Group 3 arises from lung diseases and hypoxia; Group 4 is chronic thromboembolic PH (CTEPH); and Group 5 includes unclear or multifactorial mechanisms. PH affects about 1% globally, with infectious diseases and high altitude contributing in developing countries. In the U.S., PH incidence and mortality vary by race, age, sex, region, and environmental factors like altitude and air pollution. PAH incidence is around 0.4 per 100,000 person-years, increasingly diagnosed in older adults, often with comorbidities such as obesity and sleep apnea.
Risk Factors
PH risk increases with age, peaking between 75–79 years, due to cardiovascular comorbidities and reduced cardiopulmonary function. Sex differences exist, with complex effects of hormones on disease progression and mortality. African American patients experience worse outcomes and responses to some treatments. Congenital heart disease is a notable risk factor, particularly in females. Left heart disease and lung diseases remain leading causes, with obesity, obstructive sleep apnea, and environmental exposures like air pollution contributing to PH risk.
Clinical Presentation and Diagnosis
PH often presents with exertional shortness of breath and syncope. Advanced disease causes dizziness, edema, chest pain, and signs of right heart failure. Symptoms overlap with common cardiopulmonary diseases, delaying diagnosis. Physical examination may reveal an accentuated pulmonic heart sound and signs of right heart strain. Diagnosis involves clinical assessment, imaging (echocardiography, CT pulmonary angiography), lung function tests, and confirmatory right heart catheterization, which measures pulmonary pressures. Emerging tools include AI-enhanced stethoscope recordings and advanced cardiac MRI techniques.
Treatment and Management
PH management is tailored by disease type and severity. PAH treatments include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclin analogs, and newer agents like sotatercept, which reduces clinical worsening. Investigational therapies target molecular and inflammatory pathways. Anticoagulation is key in CTEPH, which may be treated surgically by pulmonary endarterectomy or balloon angioplasty if inoperable. Multidisciplinary care, risk stratification, patient education, and rehabilitation improve outcomes.
Prognosis and Public Health
PH prognosis varies by cause and patient factors. Mortality rates have declined in the U.S., especially among congenital heart disease patients, but remain influenced by demographics and region. Most deaths are related to PH due to left heart and lung diseases. Early diagnosis and treatment improve survival. Risk calculators and patient-reported outcome measures support clinical decision-making. Public health efforts focus on early detection, risk factor modification, and addressing disparities in access to specialized care. Novel screening methods including AI are being developed to reduce diagnostic delays.
Research and Future Directions
Research focuses on epigenetic and inflammatory targets with agents like PARP-1 inhibitors, BRD4 antagonists, and IL-6 inhibitors under study. Patient-reported outcome tools enhance clinical trial assessments. Investigations also include anticoagulation strategies, stem cell therapies, and SGLT2 inhibitors. Genetic studies inform personalized approaches, especially in pediatric PAH. Advanced imaging and echocardiographic criteria improve monitoring. Ongoing trials aim to validate novel therapies, emphasizing reversal of vascular remodeling and personalized medicine to improve survival and quality of life.
The content is provided by Avery Redwood, Scopewires
