Mitral and tricuspid valve repair in hypereosinophilic syndrome

Abstract

Hypereosinophilic syndrome (HES) is a rare systemic condition, defined as a persistently elevated eosinophil count associated with end organ damage and the absence of a primary cause. Cardiac involvement occurs in about 50% of patients with HES. Myocardial infiltration results in endomyocardial fibrosis, valve dysfunction and mural thrombus. The atrioventricular valves are almost always involved, resulting in regurgitation due to leaflet restriction, most commonly affecting the posterior mitral valve leaflet. Surgical management remains challenging in patients with HES with limited data on the choice of valve surgery. We describe the case of a 17-year-old woman with HES complicated by congestive cardiac failure secondary to severe mitral and tricuspid regurgitation. Because of refractory heart failure despite medical therapy, surgical mitral and tricuspid valve repair was performed, and an excellent 24-month outcome was achieved. We believe this is the first report of double valve repair in this rare condition.

Background

Hypereosinophilic syndrome (HES) was first described by Löffler in 1936. The major cause of morbidity and mortality is from endomyocardial fibrosis, resulting in progressive restrictive cardiomyopathy or atrioventricular valve regurgitation.¹

Existing literature suggests that valve replacement in HES is associated with suboptimal outcomes. There are multiple reports of thrombosis of mechanical valves despite anticoagulant therapy.^2–4 Bioprosthetic valves may become infiltrated by eosinophilic tissue formation, which leads to premature failure.^{5 6} Little is known about the role of valve-sparing surgery in HES.

Case presentation

A 17-year-old woman presented with symptoms of biventricular failure on a background of HES. At the age of 10 years, she was found to have an elevated eosinophilic count in the context of an admission with fatigue, asthma and urticaria. Secondary causes such as parasitic infections, connective tissue disease, underlying malignancy and medications were excluded and a diagnosis of idiopathic hypereosinophilia was presumptively made. There were no symptoms of end organ damage. She was followed up and no specific treatment was commenced. At the age of 15 years, she was temporarily lost to follow-up. Eighteen months later she presented with a 2-month history of haemoptysis, dyspnoea and arthralgia. Examination revealed an apical pansystolic murmur and a palpable pulmonary closure sound with a parasternal heave. Investigations revealed hypereosinophilia (13×10⁹/L; upper limit: 0.4×10⁹/L). CT of the chest revealed diffuse interstitial pneumonitis. The platelet-derived growth factor receptor-α (PDGFRA) gene fusion mutation was not detected, and bone marrow biopsy was non-diagnostic. Transthoracic echocardiography (TTE) demonstrated severe mitral and tricuspid regurgitation. Differential diagnosis for her new valvular pathology included infection endocarditis (IE) and eosinophilic myocarditis. Repeated blood cultures were negative for an offending organism and the patient had no risk factors for IE such as intravenous drug use, poor dental health or skin infections. This, coupled with her known history of idiopathic eosinophilia made the diagnosis of eosinophilic myocarditis more likely. Treatment with intravenous hydrocortisone followed by oral prednisolone resulted in partial symptomatic improvement, and she was discharged home on 50 mg prednisolone daily. The eosinophil count remained suppressed (0.2×10⁹/L), indicating compliance with glucocorticoids. However, the patient developed worsening dyspnoea, exertional chest pain, orthopnoea and peripheral oedema, and represented 1 month later with decompensated biventricular failure. Repeat TTE and subsequent transoesophageal echocardiography (TOE) demonstrated mitral valve thickening and restriction, with a mass of tissue attached to the posterobasal left ventricular wall encasing the posterior mitral leaflet and subvalvular apparatus (figure 1A). The tricuspid valve was thickened with restricted leaflet movement (figure 1B). There was severe mitral and tricuspid regurgitation (figure 1C,D), and severe pulmonary hypertension (estimated pulmonary artery systolic pressure 76 mm Hg) associated with impaired right ventricular systolic function. Right heart catheterisation demonstrated a high pulmonary wedge pressure of 40 mm Hg, suggesting that the pulmonary hypertension was secondary to valve disease rather than intrinsic pulmonary disease.

Figure 1.

Preoperative transthoracic echocardiographic images showing mitral valve thickening and restriction, with encasement of the posterior mitral leaflet and severe mitral regurgitation (A and C). Restricted tricuspid valve with annular dilatation and severe regurgitation (B and D).

She was commenced on an intravenous diuretic (furosemide 80 mg two times per day). However, despite increasing doses of diuretics and continued prednisolone, symptomatic biventricular failure persisted and surgery was therefore undertaken. Intraoperatively, severe right ventricular dilatation and biatrial enlargement were noted. The posterior leaflet of the mitral valve was small, calcified and retracted with extensive scarring and matting of the chordae. The leaflet was repaired by partial detachment from the mitral annulus and augmentation with a strip of bovine pericardium. The anterior leaflet was mildly restricted by shortened chordae, two of which were removed, improving the mobility of the anterior leaflet. A 26 mm Profile 3D annuloplasty ring was implanted. The tricuspid valve was dilated but not fibrosed. A 30 mm physiotricuspid annuloplasty band was implanted. Post-bypass TOE confirmed satisfactory valve repairs, with no mitral and mild tricuspid regurgitation. Milrinone was administered for 12 hours postoperatively. The patient had an uncomplicated recovery to New York Heart Association class I, with no thrombotic complications. Repeat TTE 2 months postoperatively (figure 2) confirmed no mitral regurgitation and only mild tricuspid regurgitation. The patient was treated with warfarin for 3 months, and remains on prednisolone 20 mg and hydroxyurea 1 g daily. Her current eosinophil count is 0.7×10⁹/L. At 24-month follow-up, there was no recurrence of heart failure symptoms.

Figure 2.

Postoperative transthoracic echocardiographic images of the mitral valve repair. An annuloplasty ring is in situ and there is improved coaptation of the anterior mitral leaflet with the augmented posterior leaflet (A). No mitral regurgitation is apparent on colour flow Doppler (B).

Outcome and follow-up

The patient had an uncomplicated recovery to New York Heart Association class I, with no thrombotic complications. Repeat TTE 2 months postoperatively (figure 2) confirmed no mitral regurgitation and only mild tricuspid regurgitation. The patient was treated with warfarin for 3 months, and remains on prednisolone 20 mg and hydroxyurea 1 g daily. Her eosinophil count at 12 months was 0.7×10⁹/L. At 24-month follow-up, there was no recurrence of heart failure symptoms or evidence of thrombotic disease.

Discussion

HES is a rare systemic condition where three features need to be met to make the diagnosis. These are (1) persistently elevated peripheral blood eosinophil count for more than 6 months, (2) secondary and clonal causes for eosinophilia are excluded and (3) features of end organ damage.⁷ The eosinophilic infiltration, fibrosis and inflammation can target a number of organs leading to various pathological and clinical manifestations (table 1).⁸ Cardiac involvement occurs in 54%–73% of cases and is a major cause of morbidity and mortality. Myocardial infiltration results in endomyocardial fibrosis, valve dysfunction and mural thrombus. The atrioventricular valves are almost always involved, resulting in regurgitation due to leaflet restriction, most commonly affecting the posterior mitral valve leaflet. As HES is a multisystem disorder, a multidisciplinary approach is required to discuss management and decision-making regarding the need for surgery. In our case, haematology, cardiology and cardiac surgery services were involved on regular meetings to discuss the progress of this patient. Other specialities would need to be involved when other systems are affected. Medical therapy remains important in managing HES with cardiac involvement, as treatment with immunosuppressant agents leads to better outcomes both pre- and postoperatively.⁹ Reducing eosinophil count is usually achieved with systemic corticosteroids. Other agents can be used such as hydroxyurea and chlorambucil. The role of tyrosine kinase inhibitors (such as imatinib) and monoclonal antibodies (such as mepolizumab and alemtuzumab) is currently being studied. Surgical management is challenging. In this case, valve surgery was indicated on the basis of severe valvular regurgitation together with symptoms refractory to medical therapy alone. Patients with HES and mechanical valves are at higher than usual risk of thrombotic events following surgery, despite adequate anticoagulation, leading to redo surgery and high mortality rate. Activated eosinophils appear to mediate the thrombotic response via platelet aggregation, which is more likely with elevated eosinophil counts. Bioprosthetic valve replacement is preferred in HES if valve sparing is unachievable, but has also been associated with small thrombi formation. Premature failure due to eosinophilic infiltration and pannus formation can lead to early redo surgery. There are few reports of atrioventricular valve repair in HES, and none involving both mitral and tricuspid annuloplasty. Isolated mitral valve annuloplasty has been described in only two patients.^{6 10} Both had an excellent initial outcome, but in one case mitral regurgitation recurred 3 months later, necessitating subsequent bioprosthetic mitral valve replacement.¹⁰ The decision to choose valve repair or bioprosthetic replacement in patients with HES and valvular disease is limited by the lack of long-term data. Furthermore, the optimal duration of postoperative anticoagulant therapy is unknown. Further studies are needed. In young patients with HES, the risk of eventual bioprosthetic valve failure is high, and therefore valve repair where possible may be the most favourable option.

Table 1.

End organ involvement in patients with hypereosinophilic syndromes

Organ involved	Pathological manifestations	Clinical manifestation
Heart	Endocardial fibrosis, necrosis, intracardiac thrombosis, valvular dysfunction	Breathlessness, heart failure symptoms
Gastrointestinal	Eosinophilic esophagitis, gastritis and colitis	Dyspepsia, heartburn, diarrhoea (watery or blood stained) and weight loss
Neurological	Eosinophilic vasculitis	Peripheral and cranial nerves neuropathy
Skin	Eosinophilic vasculitis	Urticaria, angioedema
Respiratory	Acute and chronic eosinophilic pneumonia	Cough, breathlessness, hemoptysis
Renal	Acute interstitial nephritis	Kidney impairment

Patient’s perspective.

I appreciate I have a rare blood disorder which affected my heart. I felt very unwell when my two valves were leaking. I was happy with the outcome of my operation and glad to be free of breathlessness for more than a year now.

Learning points.

• Hypereosinophilic syndrome (HES) is a rare systemic condition. Cardiac involvement manifests as endomyocardial fibrosis, valve dysfunction and mural thrombus.

• Medical management with immunosuppressive therapy remains important in most cases.

• Despite medical therapy, significant valvular dysfunction occurs and corrective surgery is required. Surgical management of HES remains challenging with variable results in valve replacement candidates due to the risk of thrombus formation.

• Valve repair, if achievable appears to be a promising surgical strategy for this rare condition.