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Eclipsed mitral regurgitation successfully treated with a combination of surgical and pharmacological therapies: a case report

Abstract Background Eclipsed mitral regurgitation (MR), which is characterized by a transient and reversible massive functional MR, usually causes recurrent episodes of acute pulmonary oedema in patients with a preserved left ventricular ejection fraction. The pathophysiological mechanism and optimal treatment of eclipsed MR are not yet fully understood. Case summary A 72-year-old woman was hospitalized with cardiogenic shock and takotsubo cardiomyopathy. After hospitalization worsening dyspnoea again appeared, and urgent transthoracic echocardiography revealed severe MR, which spontaneously resolved in a few minutes. At this point, eclipsed MR was detected for the first time. Diagnostic examination revealed that the eclipsed MR was caused by a left ventricular afterload increase. Ultimately, the patient began medical therapy and underwent mitral valve replacement. The subsequent clinical course was favourable. Discussion This case illustrates the importance of early intervention for eclipsed MR. A combination of surgical and pharmacological therapies can serve as one treatment option for an eclipsed MR.


Introduction
Eclipsed mitral regurgitation (MR) was first reported by Avierinos et al., 1 since when only a few cases have been reported in the literature. [2][3][4] Characterized by transient and reversible massive functional MR, the clinical presentation of eclipsed MR is usually recurrent episodes of acute pulmonary oedema in patients with a preserved left ventricular ejection fraction (LVEF). Since it is a transient phenomenon rarely reported, the diagnosis is probably underestimated. In addition, the pathophysiological mechanism and optimal treatment of eclipsed MR are not yet fully understood.

Learning points
• Eclipsed mitral regurgitation (MR) can cause a life-threatening condition, such as cardiogenic shock; therefore, early intervention should be considered.
• A combination of surgical and pharmacological therapies can serve as one treatment option for an eclipsed MR.

Case presentation
A 72-year-old Japanese woman was transferred to our hospital with dyspnoea. Over the past 2 years, she had been admitted four times for heart failure requiring intensive treatment. Her medical history included paroxysmal atrial fibrillation, hypertension, and chronic kidney disease. Seven months prior, a catheter ablation was performed because paroxysmal atrial fibrillation was suspected as a trigger of the heart failure. However, after the catheter ablation, she had repeated episodes of heart failure.
On arrival at the hospital, her blood pressure was 83/34 mmHg and pulse rate 98 b.p.m. The percutaneous oxygen saturation under room air was 70%. She was dyspnoeic with poor perfusion as evident by cold extremities and poor capillary refill. Respiratory system auscultation revealed coarse crackles and wheezes bilaterally. No heart murmurs were heard. Jugular venous distention and mild peripheral oedema were observed. Arterial blood gas analysis showed metabolic acidosis with a pH of 7.11 (normal range 7.35-7.45). An electrocardiogram showed significant ST elevation in leads V2-V6 ( Figure 1A).
A chest X-ray demonstrated acute pulmonary oedema ( Figure 1B). A transthoracic echocardiogram revealed apical and mid-ventricular severe hypokinesis with an estimated LVEF of 20%, and her MR was mild. Emergent coronary angiography did not demonstrate any significant coronary artery disease. No left ventriculography was performed because her serum creatinine was 1.50 mg/dL (normal range 0.4-1.2 mg/dL). Right heart catheterization revealed a pulmonary artery pressure of 45/27/36 mmHg (normal range 15-30/4-12/9-19 mmHg), pulmonary capillary wedge pressure (PCWP) of 33 mmHg (normal range 4-12 mmHg), and cardiac index of 1.28 L/ min/m 2 (normal range 2.5-4.0 L/min/m 2 ). She was diagnosed with cardiogenic shock and acute heart failure caused by takotsubo cardiomyopathy. Intra-aortic balloon pumping (IABP) was initiated to stabilize her haemodynamic state.
On Day 3, her haemodynamic condition improved and IABP was removed successfully. A transthoracic echocardiogram demonstrated complete recovery of the left ventricular function. However, 8 days later worsening dyspnoea again appeared, and a physical examination revealed a 3/6 systolic murmur at the cardiac apex. Urgent transthoracic echocardiography revealed severe MR with tenting of the mitral leaflets, which was absent on admission. In addition, severe tricuspid regurgitation was observed, and the estimated right ventricular systolic pressure increased to 68 mmHg. A few minutes later, the MR spontaneously resolved and was only graded as mild with a normal leaflet coaptation. At this point in time transient and severe MR, termed 'eclipsed MR' in a few past reports, was suspected for the first time as the cause of the repeated heart failure episodes.
We decided to perform a diagnostic examination to investigate the cause of the eclipsed MR in the catheterization laboratory. During the test, the PCWP and central arterial pressure were monitored. At baseline, MR was mild and PCWP was in the normal range (Figures 2A and 3A). Initially, a coronary spasm provocation test was performed. Coronary angiography showed no significant stenosis after a methylergonovine infusion, and the haemodynamic parameters remained unchanged. Next the handgrip manoeuvre was performed, but this could not induce any sufficient increase in the central blood pressure. We decided to use norepinephrine, which selectively increased the systemic vascular resistance and afterload. After the norepinephrine infusion (0.07 mg/kg/min), the central arterial pressure increased dramatically. A transthoracic echocardiogram in the supine position revealed severe MR, which was absent before the test. Echocardiographic characteristics changed significantly ( Table 1). A transoesophageal echocardiogram was performed immediately and revealed severe MR with extreme apical tenting of both leaflets, resulting in a total lack of coaptation ( Figure 2B). In addition, dynamic MR led to dramatic changes in the cardiovascular haemodynamics. Right heart catheterization revealed large V waves in the pulmonary wedge pressure ( Figure 3B). With the decreasing central arterial pressure, the MR was spontaneously found to be mild on the echocardiogram.
Other investigations were also performed. Renal echography revealed the absence of any renal artery stenosis. Pheochromocytoma was ruled out by a normal plasma catecholamine level. Based on the aforementioned findings, we diagnosed that the eclipsed MR was caused by a left ventricular afterload increase. With the diagnosis and aetiology confirmed, the patient began medical therapy including beta-blockers and angiotensin-converting enzyme inhibitors aimed at decreasing the cardiac afterload. However, 6 days after starting the medications, she redeveloped severe dyspnoea and cardiogenic shock with severe acidosis secondary to eclipsed MR. Since previous reports also have described that eclipsed MR often recurs despite optimal medical therapy, 3,5 we considered that pharmacological therapy alone was difficult for management of the eclipsed MR. In addition, the eclipsed MR was considered to be more critical than we expected because the patient experienced a life-threatening condition repeatedly throughout the clinical course: in the worst case, this could lead to cardiac death. The severity of the clinical course urged us to undertake surgical therapy for our patient. After much discussion between the patient and our heart team, we decided to perform mitral surgery. On Day 43, the patient underwent mitral valve replacement using a bioprosthetic valve. The surgical findings revealed no organic changes in the mitral valve itself and mitral valve complex. The post-operative clinical course was favourable, and the patient was discharged uneventfully. Five months after the surgery, she was readmitted to our hospital for follow-up. As before, the haemodynamic parameters were monitored. We confirmed that the central blood pressure became more difficult to increase than previously after the same amount of norepinephrine infusion (0.07 mg/kg/min) ( Figure 2C). At that time, the MR was not exacerbated ( Figure 3C). One year and 3 months after surgery, the patient has been living with no recurrence of symptoms.

Discussion
Here, we have presented a case of eclipsed MR, which is characterized by transient and reversible severe MR. The clinical course of eclipsed MR usually includes recurrent unexplained acute pulmonary oedema. However, our patient repeatedly experienced a life-threatening condition, such as cardiogenic shock. Therefore, this case informed us that eclipsed MR is much more serious than might be expected, so early intervention should be considered when the cause of repeated heart failure episodes or cardiogenic shock is diagnosed as eclipsed MR.
The pathophysiological mechanism of eclipsed MR is not yet fully understood. In past reports, some authors have suggested that coronary spasms or microvascular dysfunction represent the mechanism. It has been theorized that eclipsed MR appears when coronary spasms trigger transient left ventricular dysfunction and mitral apparatus ischaemia. 6 Yet in the present case, no coronary spasms were induced and the haemodynamic parameters were unchanged after the administration of methylergonovine. However, we were able to reproduce the eclipsed MR by the administration of pharmacological