Can moderate to severe mitral regurgitation (MR) cause shortness of breath even when the left ventricular ejection fraction (LVEF) is preserved?

Moderate to Severe Mitral Regurgitation Can Cause Shortness of Breath Even with Preserved Ejection Fraction

Yes, moderate to severe mitral regurgitation can definitely cause shortness of breath (dyspnea) even when left ventricular ejection fraction is preserved. This occurs through several hemodynamic mechanisms that impact cardiac function despite normal LVEF measurements.

Pathophysiology of Dyspnea in MR with Preserved LVEF

• Mitral regurgitation creates volume overload on the left ventricle, which can lead to left atrial enlargement and pulmonary hypertension even when LVEF remains normal (>60%) 1
• The regurgitant flow into the left atrium increases left atrial pressure, which can lead to pulmonary venous congestion and symptoms of dyspnea 1
• Chronic severe MR imposes a pure volume overload on the left ventricle, resulting in eccentric hypertrophy and LV dilation, which can occur before LVEF decreases 1
• In patients with MR, LVEF may appear "normal" or even supranormal due to the reduced afterload (as blood is ejected into the lower-pressure left atrium), masking early myocardial dysfunction 1

Clinical Evidence Supporting Dyspnea in MR with Preserved LVEF

• Guidelines recognize that patients with severe MR can be symptomatic (including dyspnea/NYHA class II-IV symptoms) despite having preserved LVEF (>60%) 1
• Surgery is recommended for symptomatic patients with chronic severe MR even when LVEF is preserved (>60%), acknowledging that symptoms like dyspnea can occur before LVEF declines 1
• Mitral valve repair is reasonable for asymptomatic patients with chronic severe MR and preserved LV function who have pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg at rest or >60 mm Hg with exercise), indicating that MR can cause pulmonary pressure elevation before LVEF drops 1

Mechanisms of Dyspnea in Different Types of MR

Primary (Degenerative) MR

• In primary MR, direct valve abnormality leads to regurgitation that increases left atrial pressure and volume, which can cause pulmonary congestion and dyspnea despite preserved LVEF 2
• The European Society of Cardiology recommends surgery for symptomatic patients with severe primary MR who have LVEF >30%, recognizing that symptoms can occur at any LVEF level 2

Secondary (Functional) MR

• Even mild to moderate functional MR in patients with preserved LVEF (HFpEF) is associated with greater left atrial myopathy, more adverse pulmonary hemodynamics, and reduced cardiac output with exercise 3
• Patients with HFpEF and moderate MR show larger left atrial diameter and higher tricuspid regurgitation peak gradient (indicating pulmonary hypertension) compared to those with no/mild MR, despite similar LVEF 4

Clinical Implications and Management

• Mitral valve surgery is recommended for symptomatic patients with chronic severe MR and LVEF >30%, acknowledging that symptoms like dyspnea warrant intervention regardless of LVEF 1
• Even mild functional MR is associated with increased risk of adverse outcomes in heart failure patients with preserved EF, suggesting clinical significance even at lower grades of regurgitation 5
• The presence of symptoms (including dyspnea) in patients with severe MR is a Class I indication for surgical intervention, regardless of LVEF 1
• Echocardiographic follow-up every 6-12 months is recommended for asymptomatic patients with severe MR to monitor for development of symptoms or LV dysfunction 2

Important Caveats

• LVEF may be misleading in MR as it represents a load-dependent measure that can mask early myocardial dysfunction 1
• A "normal" LVEF in the setting of MR may actually represent early dysfunction; guidelines suggest that LVEF should ideally be >64% in severe MR 1
• The severity of MR can be dynamic and change with loading conditions, exercise, or ischemia, so symptoms may worsen during physical activity even when resting LVEF is preserved 1
• The concept of "mitral regurgitation begets mitral regurgitation" suggests that even with preserved LVEF, ongoing MR can lead to progressive LV dilation and worsening MR in a perpetual cycle 1

In conclusion, moderate to severe mitral regurgitation is a well-established cause of dyspnea even when LVEF is preserved, primarily through mechanisms of left atrial enlargement, pulmonary hypertension, and exercise-induced hemodynamic compromise.