What is the most common cause of pulmonary hypertension?

Most Common Cause of Pulmonary Hypertension

Left heart disease (Group 2 PH) is the most common cause of pulmonary hypertension worldwide, accounting for up to 70% of all pulmonary hypertension cases. 1, 2, 3

Understanding Pulmonary Hypertension Classification

Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure ≥25 mmHg at rest as measured by right heart catheterization. The clinical classification divides PH into five major groups:

1. Pulmonary arterial hypertension (Group 1)
2. PH due to left heart disease (Group 2)
3. PH due to lung diseases and/or hypoxia (Group 3)
4. Chronic thromboembolic PH (Group 4)
5. PH with unclear/multifactorial mechanisms (Group 5)

Group 2 PH: The Predominant Form

Group 2 PH (due to left heart disease) is by far the most prevalent form of pulmonary hypertension. The specific left heart conditions causing PH include:

• Heart failure with reduced ejection fraction (HFrEF): Up to 60% of patients with severe LV systolic dysfunction develop PH 1
• Heart failure with preserved ejection fraction (HFpEF): Up to 70% of these patients develop PH 1, 4
• Valvular heart disease: PH is present in virtually all patients with severe symptomatic mitral valve disease and up to 65% of those with symptomatic aortic stenosis 1
• Left atrial myopathy (often due to atrial fibrillation) 3

Pathophysiology of Group 2 PH

The development of PH in left heart disease follows a specific progression:

1. Initial stage: Passive backward transmission of elevated left atrial filling pressures into the pulmonary circulation (isolated post-capillary PH)
2. Advanced stage: With persistent elevation of pressures, pulmonary vascular remodeling occurs, adding a pre-capillary component (combined pre-capillary and post-capillary PH) 3, 4

Epidemiology and Risk Factors

Several factors increase the risk of developing Group 2 PH:

• Older age
• Female gender (especially in HFpEF)
• Hypertension
• Atrial fibrillation
• Features of metabolic syndrome 1, 5

Clinical Implications

The presence of PH in left heart disease significantly impacts prognosis:

• Worsens symptoms and exercise tolerance
• Reduces quality of life
• Associated with higher morbidity and mortality 2, 6

Diagnostic Approach

The diagnosis of Group 2 PH requires:

1. Echocardiography as initial screening
2. Right heart catheterization for definitive diagnosis with:
   • Mean PAP ≥25 mmHg
   • Pulmonary capillary wedge pressure >15 mmHg 7

Management Considerations

Treatment of Group 2 PH focuses primarily on addressing the underlying left heart disease:

• Guideline-directed medical therapy for heart failure
• Surgical or percutaneous management of valvular disorders
• Control of modifiable risk factors and comorbidities 3

Important Caveat

While pulmonary vasodilator therapies (used in Group 1 PH) have been investigated for Group 2 PH, results have been largely disappointing and sometimes harmful. These medications should generally be avoided in Group 2 PH unless part of a clinical trial or in specialized centers with extensive experience 4.