Can pulmonary hypertension be caused by mitral regurgitation (MR) and diastolic dysfunction?

From the Guidelines

Pulmonary hypertension can indeed be caused by mitral regurgitation and diastolic dysfunction, as these conditions lead to increased left atrial pressure, which in turn causes pulmonary venous hypertension and eventually pulmonary arterial hypertension. When the mitral valve leaks (regurgitation), blood flows backward into the left atrium during systole, increasing left atrial pressure 1. Similarly, diastolic dysfunction impairs the left ventricle's ability to fill properly during diastole, also leading to increased left atrial pressure 1. This elevated left atrial pressure transmits backward into the pulmonary veins and pulmonary circulation, causing pulmonary venous hypertension. Over time, this increased pressure in the pulmonary vasculature leads to pulmonary arterial hypertension, classified as WHO Group 2 pulmonary hypertension (due to left heart disease) 1.

The primary treatment approach focuses on addressing the underlying cardiac conditions rather than using pulmonary vasodilators. Management typically involves:

• Optimizing heart failure therapy with medications like ACE inhibitors, beta-blockers, and diuretics
• Considering surgical repair of the mitral valve if regurgitation is severe 1 This type of pulmonary hypertension is particularly important to recognize because its treatment differs significantly from other forms of pulmonary hypertension, with the focus being on correcting the left-sided cardiac abnormalities 1. According to the 2015 ESC/ERS guidelines, PH-LHD can complicate any left heart disorder, such as valvular heart diseases and congenital defects, and often results in more severe symptoms and worse exercise tolerance and exerts a negative impact on outcome 1.

From the Research

Pulmonary Hypertension Causes

• Pulmonary hypertension (PH) can be caused by various factors, including mitral regurgitation and diastolic dysfunction 2, 3, 4, 5, 6
• Mitral regurgitation allows for partial transmission of systemic arterial pressure into the pulmonary venous system, leading to pressurization of the pulmonary venous system and potentially causing PH 2
• Diastolic dysfunction can also contribute to PH by increasing resistance to filling and leading to diastolic dysfunction in the right ventricle (RV) 6

Relationship Between Mitral Regurgitation and Pulmonary Hypertension

• Studies have shown that mitral regurgitation is associated with increased mortality in patients with PH, and that the severity of mitral regurgitation correlates with long-term survival 3, 5
• Exercise echocardiography has been used to depict PH in asymptomatic patients with mitral regurgitation, and has shown that PH is observed in about 40% of these patients 4
• The impact of concomitant mitral regurgitation on systolic pulmonary artery pressure (SPAP) decreases at higher transmitral gradients and is no longer significant at gradients ≥10 mm Hg 5

Role of Diastolic Dysfunction in Pulmonary Hypertension

• Diastolic dysfunction can increase resistance to filling and lead to diastolic dysfunction in the RV, contributing to PH 6
• Beta1-adrenergic receptor blockers (BB) have been shown to improve diastolic function, partially restore metabolic enzymes, and augment contractility in PAH, suggesting a potential therapeutic benefit 6
• The expression of creatine kinase protein and mRNA is lower in PAH rats compared to controls, with a trend for reversion by BB treatment, indicating a potential role for BB in improving RV function 6