From the Guidelines
Out of proportion pulmonary hypertension is primarily caused by left heart disease, particularly left ventricular diastolic dysfunction and mitral valve disease, as well as other conditions such as lung diseases, chronic thromboembolic disease, and pulmonary arterial hypertension (PAH) 1. The primary causes of out of proportion pulmonary hypertension include:
- Left heart disease (particularly left ventricular diastolic dysfunction and mitral valve disease)
- Lung diseases (such as COPD, interstitial lung disease, and sleep-disordered breathing)
- Chronic thromboembolic disease
- Pulmonary arterial hypertension (PAH) In left heart disease, backward transmission of pressure leads to pulmonary venous congestion, while lung diseases cause hypoxic vasoconstriction and destruction of the pulmonary vascular bed 1. Chronic thromboembolic disease results in mechanical obstruction of pulmonary vessels, and PAH involves pathological changes in small pulmonary arteries including endothelial dysfunction, smooth muscle proliferation, and inflammation 1. Additional contributing factors include genetic predisposition (particularly mutations in BMPR2 gene), autoimmune disorders, certain drugs and toxins (like methamphetamines and certain diet pills), portal hypertension, and HIV infection 1. The pathophysiology involves vasoconstriction, vascular remodeling, inflammation, and thrombosis, leading to increased pulmonary vascular resistance and eventual right heart failure if left untreated 1. It is worth noting that the term "out of proportion PH" has been abandoned in recent guidelines, and instead, the focus is on identifying the underlying cause of pulmonary hypertension and managing it accordingly 1.
From the Research
Causes of Out of Proportion Pulmonary Hypertension
- Out of proportion pulmonary hypertension, also known as combined pre- and post-capillary PH (Cpc-PH), is a condition where pulmonary vascular disease is present, leading to increased mortality 2.
- This condition is characterized by a diastolic pulmonary vascular pressure gradient ≥ 7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure 2.
- The causes of Cpc-PH are not fully understood, but it is thought to be related to pulmonary vascular disease, which can be caused by a variety of factors, including chronic heart failure, valvular heart disease, and chronic obstructive pulmonary disease (COPD) 2.
- In patients with heart failure with preserved ejection fraction (HFpEF), Cpc-PH can occur due to "precapillary" alterations of pulmonary vasculature, which can be partially reversible and serves as a therapeutic target 3.
Risk Factors for Out of Proportion Pulmonary Hypertension
- Chronic obstructive pulmonary disease (COPD) is a predictor of Cpc-PH in patients with systolic heart failure (SHF) 2.
- Younger age, valvular heart disease, and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio are predictors of Cpc-PH in patients with diastolic heart failure (DHF) 2.
- Right ventricular-pulmonary vascular coupling is poor in Cpc-PH patients, which could be one explanation for dismal outcomes 2.
Diagnosis and Treatment of Out of Proportion Pulmonary Hypertension
- The diagnosis of Cpc-PH is based on the accurate measurement of pulmonary arterial wedge pressure and invasive confirmation of PH-LHD 4.
- Treatment of Cpc-PH may include optimized management of heart failure, sufficient volume control, catheter-based mitral valve repair, and targeted PH therapy, such as phosphodiesterase (PDE) inhibitors 5, 3.
- PDE type 5 inhibitors have been shown to be effective in decreasing pulmonary artery pressure and improving RV contractility in patients with Cpc-PH and HFpEF 3.