Every Now and Then I Fall Apart: Total Eclipse of the Mitral Valve

The severity of mitral regurgitation (MR) is known to be sensitive to afterload and preload. The term “eclipsed mitral valve” is used to describe dynamic MR, particularly in post-menopausal women with microvascular dysfunction.^[1] We report a case of dynamic MR causing recurrent severe symptoms.

CASE:

A 74 year old woman presented with progressive exertional breathlessness. Exam was unremarkable. Local echocardiogram was notable for Grade 1 diastolic dysfunction, normal ejection fraction (EF), and mild MR. Coronary angiogram showed non-obstructive disease, but sluggish flow suggesting microvascular disease. Right heart catheterization (RHC) revealed normal filling pressures, pulmonary artery (PA) pressures, and cardiac output at rest. With exercise, systolic PA pressure increased to 82, but the PA wedge pressure (PCWP) was normal at 13 mmHg. She was diagnosed with Group 1 exercise-induced Pulmonary Hypertension (PH) and started on sildenafil. Symptoms worsened and sildenafil was discontinued, with initiation of macitentan. Four days later, she had severe dyspnea prompting a call to Emergency Medical Services and was intubated. Findings were consistent with flash pulmonary edema of unclear etiology. Repeat echocardiogram showed mild-moderate MR.

After dismissal, she sought a second opinion and was referred RHC with exercise and concurrent echocardiography (Figure 1). At baseline there was mild MR (Video 1), with borderline elevated filling pressures and PA pressures. With feet up, she felt dyspneic. PCWP increased with V wave to 65 mmHg (Figure 2). MR became severe on echocardiogram (Video 2). Nitroglycerin was administered, with normalization of filling pressures and resolution of symptoms. With exercise testing she again became severely dyspneic, with development of giant V waves in PCWP with torrential MR on echocardiogram (Figure 3, Video 3). Cardiac output increased by only 0.3 L/min during exercise. Subsequent transesophageal echocardiogram revealed a normal appearing mitral valve with trivial MR, but with leg raise there was torrential central MR (Video 4).

Figure 1. Invasive Hemodynamics and Echocardiogram at Rest.

Upper panel shows PCWP and RA tracings with normal values at rest. Bottom left panel shows apical long axis view with color flow Doppler showing mild MR. Bottom right panel shows CW Doppler through the mitral valve with mild MR jet as well as the arterial tracing showing a broad waveform consistent with normal forward stroke volume.

CW = continuous wave; MR = mitral regurgitation; PCWP = Pulmonary Capillary Wedge Pressure; RA = right atrium

Figure 2. Invasive Hemodynamics and Echocardiogram with Feet Up.

With feet up, upper panel shows marked V waves in the PCWP to 65 mmHg. Bottom left panel shows moderate-severe MR. Bottom right panel shows MR is at least moderate-severe by density of CW Doppler along with lower peak Doppler velocity. In addition, the arterial tracing is less broad, suggesting lower forward stroke volume.

CW = continuous wave; MR = mitral regurgitation; PCWP = Pulmonary Capillary Wedge Pressure; RA = right atrium

Figure 3. Invasive Hemodynamics and Echocardiogram with 20 Watts Exercise.

With 20 Watts exercise, PCWP V waves increasing further to 74 mmHg. Bottom left panel shows severe MR. Bottom right panel shows MR is now torrential by CW Doppler with triangular shape suggesting rapid equalization of pressure between left ventricle and left atrium. With this increase in regurgitant volume the arterial tracing waveform suggests even lower forward stroke volume.

CW = continuous wave; MR = mitral regurgitation; PCWP = Pulmonary Capillary Wedge Pressure; RA = right atrium

The patient was diagnosed with severe MR due to an eclipsed mitral valve and underwent bioprosthetic mitral valve replacement. Four months postoperatively she was asymptomatic.

DISCUSSION:

In patients with preserved EF and exertional breathlessness, invasive hemodynamic exercise testing with echocardiogram can provide valuable diagnostic insights. Heart failure with preserved EF (HFpEF) is the most common etiology revealed at exercise testing in this population, but a broad differential must be considered when findings are not typical. While resting findings were normal, increased preload seemed to provoke her symptoms, both by history (decompensation with pulmonary vasodilators) and in the laboratory (increased venous return due to feet elevation or supine exercise). Conversely, preload reduction with nitrates reduced the MR. The hemodynamics were notable for marked elevation of the PCWP tracing with large V waves. Patients may develop prominent V waves with increased inflow of blood through the pulmonary veins when the left atrium is stiff, or with increased retrograde flow of blood due to MR with a functionally normal atrium. Concurrent echocardiogram in this case confirmed that the V wave was caused by MR. The historical diagnosis of PH as being of precapillary mechanism was incorrect. This highlights the importance of careful assessment of PCWP at rest and with provocative maneuvers, importance of simultaneous echocardiogram during invasive hemodynamic assessment, and the value of repeating testing when diagnostic uncertainty persists.

Mitral regurgitation is known to be sensitive to changes in loading. Mild or moderate MR at rest in patients with HFpEF is not uncommon and typically reflects underlying LA myopathy (“atrial MR”).^[2] However, this atrial MR is rarely associated with such a dramatic presentation. Eclipsed mitral valve was first described in 2008 and few cases have been reported. The true prevalence and etiology are unknown. Eclipsed mitral valve was first thought to be related to epicardial coronary vasospasm causing ischemic MR, but it has been shown to occur in patients without vasospasm.^{[1, 3–5]} The majority of patients are postmenopausal women, often with microvascular dysfunction, which is now well-recognized to be prevalent in HFpEF.^[6–9] The combination of diastolic dysfunction and microvascular coronary disease can decrease coronary perfusion pressure.^[10] If there is microvascular ischemia in one or both papillary muscles, this could promote or exacerbate MR. In addition, there may also be mitral annular dilation causing severe MR,[3] due to increases in left ventricular or atrial volume.^[2] Figure 4 shows a possible pathophysiologic model. What remains unknown is what separates these patients from the majority of patients with microvascular disease and HFpEF who do not develop dynamic MR. There may be an anatomic abnormality not yet defined, be it of the mitral valve or coronary anatomy.

Figure 4: Proposed pathophysiologic model for eclipsed mitral valve.

In setting of a structurally normal mitral valve, patients with microvascular disease and left ventricular (LV) diastolic dysfunction are more sensitive to stressors that lead to volume loading (e.g. feet up, exercise). This increases filling pressures and dilates the left atrium, LV and mitral annulus, causing mitral regurgitation (MR). This increases intracardiac pressures and leads to a decrease in forward stroke volume, reducing diastolic blood pressure, and therefore further decreasing coronary perfusion pressure. In the setting of pre-existing coronary microvascular disease, this can initiate a vicious cycle leading to worsening MR and elevation in filling pressures.

HFpEF = Heart failure with preserved ejection fraction; LV= left ventricle; MR = mitral regurgitation; PM = papillary muscle

In summary, MR can be dynamic in response to volume loading. In patients with exertional breathlessness, invasive exercise testing with echocardiography is essential in the diagnostic evaluation. More study is needed to better assess the prevalence, natural history and optimal treatment for dynamic MR and the mechanisms underlying it.