What are examples of group 2 pulmonary hypertension?

Group 2 Pulmonary Hypertension: Clinical Examples

Group 2 pulmonary hypertension is defined as PH due to left heart disease, characterized by elevated left-sided filling pressures causing backward transmission into the pulmonary circulation. 1

Specific Clinical Conditions in Group 2 PH

Left Ventricular Dysfunction

Systolic dysfunction:

• Left ventricular systolic dysfunction with reduced ejection fraction (HFrEF) is a major cause of Group 2 PH 1
• Up to 60% of patients with severe LV systolic dysfunction develop pulmonary hypertension 1
• Commonly results from ischemic heart disease and systemic hypertension 2

Diastolic dysfunction:

• Left ventricular diastolic dysfunction with preserved ejection fraction (HFpEF) 1
• Up to 70% of patients with heart failure with preserved ejection fraction may present with PH 1
• Develops as a consequence of impaired left ventricular relaxation and distensibility 2

Valvular Heart Disease

Mitral valve disease:

• PH can be found in virtually all patients with severe symptomatic mitral valve disease 1
• Mitral stenosis was historically the most frequent cause of PH several decades ago 2
• Mitral regurgitation also causes elevated left atrial pressures leading to PH 1

Aortic valve disease:

• Up to 65% of patients with symptomatic aortic stenosis develop pulmonary hypertension 1
• The prevalence of PH increases with the severity of the valvular defect and symptoms 1

Structural Left Heart Abnormalities

Congenital/acquired obstructions:

• Congenital or acquired left heart inflow/outflow tract obstruction 1
• Congenital cardiomyopathies 1
• Congenital or acquired pulmonary vein stenosis 1

Hemodynamic Characteristics

Group 2 PH is characterized by post-capillary pulmonary hypertension with specific hemodynamic criteria:

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest 1
• Pulmonary arterial wedge pressure (PAWP) >15 mmHg, reflecting elevated left-sided filling pressures 1, 3

Two hemodynamic subtypes exist within Group 2:

• Isolated post-capillary PH (IpcPH): PAWP >15 mmHg with diastolic pressure gradient (DPG) <7 mmHg and/or pulmonary vascular resistance (PVR) ≤3 Wood units 3
• Combined pre- and post-capillary PH (CpcPH): PAWP >15 mmHg with DPG ≥7 mmHg and/or PVR >3 Wood units, indicating additional pulmonary vascular remodeling 3

Clinical Significance

Group 2 PH is the most common form of pulmonary hypertension globally:

• Left heart disease is believed to be the most common cause of PH, affecting approximately 1% of the global population 4
• The prevalence of PH in patients with chronic heart failure increases with the progression of functional class impairment 1
• CpcPH occurs in 12-13% of patients with post-capillary PH and is associated with poor prognosis 3

Pathophysiological Distinction

The mechanism differs fundamentally from Group 1 pulmonary arterial hypertension:

• Chronic sustained elevation of left-sided pressures causes retrograde transmission to pulmonary capillaries 2, 5
• This leads to lung capillary injury, pulmonary vascular remodeling in some cases, and eventual right ventricular overload 2
• These pathophysiological differences explain why Group 2 PH patients respond poorly to PAH-specific therapies 5