© 2014 Wiley Periodicals, Inc.
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Tricuspid Valve Surgery in Patients With Idiopathic Hypereosinophilic Syndrome Josef Besik, M.D., Ph.D.,* Ondrej Szarszoi, M.D., Ph.D.,* Ivan Netuka, M.D., Ph.D.,* Ludek Voska, M.D.,y and Jan Pirk, M.D., Ph.D.* *Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; and yDepartment of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic ABSTRACT: A 53-year-old female with idiopathic hypereosinophilic syndrome underwent recurrent tricuspid valve replacement for Lo¨ffler’s endocarditis. We review the literature on tricuspid valve surgery in patients with this uncommon disorder. doi: 10.1111/jocs.12483 (J Card Surg 2015;30:140–144) Idiopathic hypereosinophilic syndrome (iHES) is an uncommon leukoproliferative disorder that can cause multiple organ damage by eosinophilic infiltration. Cardiovascular complications of iHES are a major source of morbidity and mortality.1 Cardiac involvement is characterized by endocardial fibrosis and mural thrombi, leading to restrictive cardiomyopathy and valvular dysfunction known as Lo¨ffler’s endocarditis.2 PATIENT PROFILE A 53-year-old female was admitted with dyspnea on exertion (New York Heart Association class III). Signs and symptoms of right cardiac failure were observed. Transthoracic (TTE) and transesophageal echocardiography (TEE), computed tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography (PET) were performed. These examinations revealed a large solid mass in the right ventricle with no metabolic activity arising from the right ventricular free wall. This huge mass filled the right ventricle, which was almost obliterated (Fig. 1), and involved the tricuspid valve, causing severe tricuspid stenosis. Endomyocardial biopsy via the right internal jugular vein revealed a thrombus. Tumor marker levels (alpha-1-fetoprotein, CA 19–9, CEA, CA 125) were within normal ranges, as were other laboratory values,
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Josef Besik, M.D., Ph.D., Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 00, Prague 4, Czech Republic. Fax: 00420236052776; E-mail: [email protected]
including the blood count and eosinophils level. However, untreated intermittent hypereosinophilia of unknown origin was the only diagnostic clue in the patient’s medical history. Due to rapid right heart failure progression and hemodynamic deterioration, cardiac surgery was indicated. Surgery was performed through median sternotomy using standard cardiopulmonary bypass with bicaval cannulation without aortic cross clamping and cardioplegic arrest. The right atrium was opened. The tricuspid valve was almost completely attached to the surrounding thrombotic mass and was entirely immobile, with just a small residual opening allowing for atrioventricular communication. The tricuspid valve was excised together with the suspensory apparatus and the mass which filled the entire right ventricle. Tricuspid valve replacement was performed with a 31 mm Carpentier-Edwards Perimount pericardial bioprosthesis (Edwards Lifesciences, Irvine, CA, USA). Histological examination of the mass removed from the right ventricle revealed fibrous, thrombotic and necrotic tissue with residual inflammatory cell infiltration. The patient tolerated the procedure well, and a predischarge TTE showed no pathological findings. The function of the bioprosthesis was normal (gradient 6/ 2 mmHg). The patient was in stable cardiopulmonary condition, placed on Coumadin therapy, and discharged to home care. Four months after the operation, the patient presented again with dyspnea on exertion (NYHA class II) and signs and symptoms of right cardiac failure. Laboratory findings showed a white blood cell count of 13,200 per mm3, with 57% eosinophils (eosinophile count 7,524 per mm3). A diagnosis of idiopathic hypereosinophilic syndrome was confirmed. Medical
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Figure 1. Transthoracic echocardiography showing a pathological mass (white arrow) filling the right ventricle (Ao, aorta; LA, left atrium; LV, left ventricle).
Figure 3. Photograph showing the explanted bioprosthesis viewed from the atrial aspect. The leaflets of the valve are connected by tough fibrotic tissue.
therapy with Imatinib, corticosteroids, digitalis, beta blockers, and diuretics was started. An echocardiogram showed normal systolic function of both ventricles. The leaflets of the tricuspid valve prosthesis were thick (3–4 mm), adhered and exhibited restricted movement. A gradient of 17/8 mmHg was consistent with significant tricuspid stenosis. No abnormal mass, such as a thrombus or vegetation, was present. Despite treatment, one month later (five months after the primary operation), the patient was referred for surgery due to further progression of right-sided heart failure. After performing a resternotomy and connecting the patient to extracorporeal circulation, the right atrium was opened and the degenerated pericardial bioprosthesis was replaced with a 31 mm St Jude Medical Epic porcine bioprosthesis (St Jude Medical, Inc, St Paul, MN, USA). Beating heart surgery was complicated by the development of a third-degree atrioventricular block, requiring the implantation of a permanent pacemaker 18 days after the surgery. The explanted valve (Figs. 2 and 3) and a sample of the surrounding tissue were sent to histology for examination. The removed valve wall contained fibrotic tissue with no
involvement of eosinophils. A sample of the surrounding tissue contained significantly thickened endocardium, which was partially composed of acellular fibrous tissue and fibrous vascularized nonspecific granulation tissue. The adjacent myocardium showed edema and mild fibrosis of the interstitium, with no inflammatory cell infiltration (Fig. 4). The patient tolerated the second operation well. A pre-discharge TTE showed a peak gradient of 11 mmHg, mean gradient of 4 mmHg, and no regurgitation. The patient was discharged in good condition. Coumadin was discontinued and instead she was prescribed lowmolecular-weight heparin (LMWH). In the postoperative period, the patient was regularly monitored for control of peripheral eosinophilia. Hypereosinophilia relapses were successfully treated by temporarily increasing the dose of Imatinib and corticosteroids. Now, over nine years since the second operation, the patient is in stable cardiopulmonary condition and feels well. She is on continued therapy with Imatinib, corticosteroids, digitalis, beta blockers, diuretic, and LMWH. The bioprosthesis in the tricuspid position shows no signs of dysfunction and has stable
Figure 2. Photograph showing the explanted bioprosthesis. Mural thrombi are visible on the side originally facing the right ventricle.
Figure 4. A histology of the excised bioprosthesis (hematoxylin and eosin stain, 20x magnification) shows the morphology of collagenous connective tissue (red) and parietal thrombosis (pink). No eosinophils were found.
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parameters (peak gradient 12 mmHg, mean gradient 4 mmHg).
DISCUSSION Idiopathic hypereosinophilic syndrome is a rarely seen leukoproliferative disorder characterized by unexplained prolonged peripheral eosinophilia with organsystem dysfunction due to eosinophillic infiltration.1 The diagnosis of iHES is based on marked eosinophilia (up to 1,500 cells per mm3) for at least six months while excluding other causes of eosinophilia, which particularly include parasitic infections, hypersensitivity reactions or neoplastic diseases. It may affect practically any organ, and often two or more organs may be affected concurrently.3 Cardiac dysfunction is the most frequent result of end-organ damage (from 54% to 95% of cases)3,4,5 and is the major cause of morbidity and mortality among iHES patients.1 iHES also can affect the nervous system (40–64%), skin (56%), and pulmonary system (40–49%). Less frequently, the gastrointestinal tract, liver, spleen, and ocular system are involved.3,4,5 Idiopathic hypereosinophilic syndrome is more common in men than in women (9:1). Prevalence is most frequent between the 20 and 50 years of age.1 The etiology of iHES is unknown. The most frequently cited causes of iHES are the overproduction of cytokines involved in eosinophilic growth and differentiation, a cytokine disorder featuring enhanced or extended bioactivity, or possible defects in the receptors for these cytokines.1,5 Tissue damage is then caused by the release of various cytotoxic mediators and enzymes from the activated eosinophils. Further contributing to tissue damage are impaired coagulation and increased platelet aggregation, which is also caused by activated eosinophils and eosinophil factors.6 In the heart, eosinophilic infiltration and the production of eosinophil peroxidases usually result in restrictive cardiomyopathy with endocardial fibrosis, mural thrombi, and atrioventricular valve dysfunction.7 Cardiac lesions may occur in either the left or right side or in both. This impairment to the heart was first described by Lo¨ffler in Zurich in 1936 when he documented the cases of two patients with marked sustained peripheral eosinophilia and an unusual type of endomyocardial fibrosis, which is known as Lo¨ffler’s endocarditis.2 Since then, several dozen cases of patients with hypereosinophilia and concurrent cardiac impairment have been described. Its defining characteristic is a finding of endocardial fibrosis, which causes impaired ventricular diastolic relaxation and the presence of intracavitary thrombotic masses, which often significantly reduce ventricular cavity size. Both of these pathological changes result in reduced ventricular filling and the development of forms of congestive heart failure similar to that found in constrictive pericarditis.4,8 The third characteristic of the pathology, damage to the atrioventricular valve, is found in patients where endocardial fibrosis extends to involve the papillary muscles and chordae tendineae, producing mitral or tricuspid insufficiency or stenosis.9
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Treatment of the hypereosinophilic syndrome attempts to limit organ damage by controlling the eosinophil count with aggressive therapy consisting of prednisone, hydroxyurea, interferon alpha, and cytotoxic chemotherapy.10 This medical therapy improves the survival rate to 4% mortality after three years, compared to a 77% mortality within three years without medical therapy.11 Recent studies reported the efficacy of 100 to 400 mg Imatinib daily in HES patients.10,12 Imatinib mesylate (Gleevec, Novartis) is a 2-phenyl-aminopyrimidine-based tyrosine kinase inhibitor. It also inhibits some receptors possibly involved in the pathogenesis of iHES, such as the type III transmembrane receptors KIT or platelet-derived growth factor receptors (PDGFR).10 The reported adverse effects of Imatinib were only mild with a remarkable low incidence of hematological toxicity.12 Surgical experience with valve defects in iHES patients is limited because these defects play a rather minor role in the course and prognosis of the disease when compared to the extent and progression of endomyocardial fibrosis and associated heart failure.9 In 1991, Boustany presented eight cases of iHES patients who underwent mitral valve surgery (seven valve replacements and one mitral valve annuloplasty).13 In 2005, Fuzellier11 published another summary of mitral valve operations in 14 patients, 12 of whom underwent mitral valve replacement and two mitral valve repair. It was shown that mechanical valves in iHES patients have a high incidence of obstructive thrombosis, leading to reoperation and high mortality; bioprosthesis was therefore recommended in cases of mitral valve replacement.11 Tricuspid surgical experience in patients with idiopathic hypereosinophilic syndrome is very limited. Only single cases of tricuspid valve surgery have been published to date (Table 1). Three of ten patients died in a short time after surgery. One patient died six hours after the operation and one died seven months after the operation, both due to right heart failure. One patient died eight months after the operation due to prosthetic valve endocarditis and subsequent sepsis. In most patients (7 cases of 10), the reason for the tricuspid valve procedure was significant regurgitation; stenosis was the dominant pathology in only three cases. Three patients underwent isolated tricuspid valve surgery;14–16 in the other seven cases, a procedure was performed on the mitral valve concurrently with the tricuspid valve surgery. In half of the cases, the tricuspid valve was successfully repaired, while tricuspid valve replacement was required in half of the patients, with four receiving a biological replacement and just one a mechanical replacement.17 This patient’s mitral valve was concurrently replaced with a mechanical prosthesis, but in the postoperative period, he experienced obstructive thrombosis in both mechanical valves and both mechanical valves had to be replaced with biological prostheses (four months after the primary operation). Despite Coumadin therapy, the iHES patients experience thrombosis, even in those with biological valve replacements.11,18 Burstow et al.15 describe the case of a 52-year-old male who developed
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TABLE 1 Tricuspid Valve Surgery in Hypereosinophilic Endocarditis No
Year
Author
Procedure
Tri Path
Surg.
Age
Gen
1 2 3 4 5 6 7 8 9 10
1977 1981 1982 1982 1985 1997 1999 2006 2008 2011
Weyman9 Davies19 Harley17 Harley17 Cameron20 Metzler21 Imoto14 Burstow15 Carnero-Alcazar16 Chu18
MVR þ TVP MVR þ TVR MVR þ TVR MVR þ TVR MVR þ TVR MVP þ TVP TVP TVR TVP MVR þ TVP
Stenosis Regurg. Regurg. Stenosis Regurg. Regurg. Regurg. Stenosis Regurg. Regurg.
Repair Bio Mech Bio Bio Repair Repair Bio Repair Repair
35 36 24 29 45 28 25 52 62 78
F M M M M M M M M F
Follow-Up 6 months, alive 7 months, alive Died* 21 months, alive Died** 20 months, alive 26 days, alive 46 months, alive Died*** 2 months, alive
No ¼ number of case; Tri path ¼ tricuspid valve pathology; Surg. ¼ type of surgery; Gen ¼ gender; MVR ¼ mitral valve replacement; MVP ¼ mitral valve repair; TVR ¼ tricuspid valve replacement; TVP ¼ tricuspid valve repair; regurg. ¼ regurgitation; Bio ¼ bioprosthesis; Mech ¼ mechanical valve; F ¼ female; M ¼ male. * Patient died 8 months after operation—prosthetic valve endocarditis. ** Patient died 7 months after operation—right heart failure. *** Patient died 6 hours after operation—right heart failure.
bioprosthetic dysfunction in the tricuspid position 20 months following implantation. The patient’s condition required reoperation and replacement of the prematurely degenerated bioprosthesis with another bioprosthesis. Significant stenosis developed in this second bioprosthesis in 26 months, when balloon valvuloplasty was performed with a very good immediate effect. In our patient, the bioprosthesis prematurely degenerated with mural thrombosis less than five months from implantation. However, after starting adequate iHES therapy and with regular long-term control of eosinophilia, the patient is in good condition nine years following the second tricuspid valve replacement with no signs of prosthetic dysfunction. Due to the increased risk of thrombosis, tricuspid valve repair should be preferred in iHES patients if technically feasible. In cases where the tricuspid valve must be replaced, preference should be given to a bioprosthesis over a mechanical valve despite the young age of the patient, as mechanical valves are more susceptible to thrombus formation.6,11 Our experience leads us to believe that tricuspid valve replacement with a bioprosthesis in a patient with idiopathic hypereosinophilic syndrome is feasible with good long-term results assuming there is appropriate anticoagulation and regular perioperative and postoperative control of peripheral eosinophilia to minimize the risk of prosthetic valve thrombosis.
5.
6.
7.
8. 9.
10.
11.
12.
13.
REFERENCES 1. Weller PF, Bublej GJ: The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759–2779. 2. Lo¨ffler W: Endocarditis parietalis fibroplastica mit bluteosinophilie, ein eigenartiges krankheitsbild. Schweiz Med Wschr 1936;66:817–820. 3. Fauci AS, Halley JB, Roberts WC, et al: The idiopathic hypereosinophilic syndrome. Ann Intern Med 1982;97: 78–92. 4. Chusid MJ, Dale DC, West BC, et al: The hypereosinophilic syndrome: Analysis of fourteen cases with
14.
15.
16.
review of the literature. Medicine (Baltimore) 1975;54: 1–27. Gotlib J, Cools J, Malone JM, et al: The FIP1L1PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: Implications for diagnosis, classification, and management. Blood 2004;103:2879–2891. Mizota T, Miyawaki I, Enoki T, et al: Massive prosthetic valve trombus in a patient with idiopathic hypereosinophilic syndrome. J Cardiothorac Vasc Anesth 2007;21: 434–435. De Rock C, Lemaitre J, Deuvaert FE: Loeffler endomyocarditis: A clinical presentation as right ventricular tumor. J Heart Valve Dis 1998;7:668–671. Brink AJ, Weber HW: Fibroblastic parietal endocarditis with eosinophilia. Am J Med 1963;34:52–70. Weyman AE, Rankin R, King H: Loeffler’s endocarditis presenting as mitral and tricuspid stenosis. Am J Cardiol 1977;40: 438–444. Cools J, DeAngelo DJ, Gotlib J, et al: A Tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of Imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201–1214. Fuzellier JF, Chapoutot L, Torossian PF: Mitral valve replacement in idiopathic eosinophilic endocarditis without peripheral eosinophilia. J Card Surg 2005;20:472– 474. Metzgeroth G, Walz C, Erben P, et al: Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome: A phase II study. Br J Haematol 2008;143:707–715. Boustany CW Jr, Murphy GW, Hicks GL Jr: Mitral valve replacement in idiopathic hypereosinophilic syndrome. Ann Thorac Surg 1991;51:1007–1009. Imoto Y, Tominaga R, Morita S, et al: Surgical treatment of tricuspid regurgitation caused by Lo¨ffler’s endocarditis. Jpn J Thorac Cardiovasc Surg 1999;47:570–573. Burstow DJ, West ML, Walters DL: Intracardiac echo guided valvuloplasty of a stenotic tricuspid prosthetic valve in a patient with idiopathic hypereosinophilic syndrome. Echocardiography 2006;23:324–328. ´ Connor F, et al: Carnero-Alcazar M, Reguillo-Lacruz F, O Hypereosinophilic syndrome and myocardial fibrosis. Interact Cardiovasc Thorac Surg 2008;7:928–930.
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17. Harley JB, McIntosh CL, Kirklin JJ, et al: Atrioventricular valve replacement in the idiopathic hypereosinophilic syndrome. Am J Med 1982;73:77–81. 18. Chu MWA, Adams C, Yared K, et al: Reoperative minimally invasive mitral valve replacement for bovine pericardial valve thrombosis secondary to idiopathic hypereosinophilic syndrome. Can J Cardiol 2011;27:868. e11–868.e13.
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19. Davies J, Sapsford R, Brooksby I, et al: Succesful surgical treatment of two patients with eosinophilic endomyocardial disease. Br Heart J 1981;46:438–445. 20. Cameron J, Radford DJ, Howell J, et al: Hypereosinophilic heart disease. Med J Aust 1985;143:408–410. 21. Metzler B, G@ unther E, Perier P, et al: Lo¨ffler´s parietal fibroplastic endocarditis. Echocardiographic course over 5 years. Dtsch Med Wochenschr 1997;122:182–187.
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Tricuspid Valve Surgery in Patients With Idiopathic Hypereosinophilic Syndrome Josef Besik, M.D., Ph.D.,* Ondrej Szarszoi, M.D., Ph.D.,* Ivan Netuka, M.D., Ph.D.,* Ludek Voska, M.D.,y and Jan Pirk, M.D., Ph.D.* *Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; and yDepartment of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic ABSTRACT: A 53-year-old female with idiopathic hypereosinophilic syndrome underwent recurrent tricuspid valve replacement for Lo¨ffler’s endocarditis. We review the literature on tricuspid valve surgery in patients with this uncommon disorder. doi: 10.1111/jocs.12483 (J Card Surg 2015;30:140–144) Idiopathic hypereosinophilic syndrome (iHES) is an uncommon leukoproliferative disorder that can cause multiple organ damage by eosinophilic infiltration. Cardiovascular complications of iHES are a major source of morbidity and mortality.1 Cardiac involvement is characterized by endocardial fibrosis and mural thrombi, leading to restrictive cardiomyopathy and valvular dysfunction known as Lo¨ffler’s endocarditis.2 PATIENT PROFILE A 53-year-old female was admitted with dyspnea on exertion (New York Heart Association class III). Signs and symptoms of right cardiac failure were observed. Transthoracic (TTE) and transesophageal echocardiography (TEE), computed tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography (PET) were performed. These examinations revealed a large solid mass in the right ventricle with no metabolic activity arising from the right ventricular free wall. This huge mass filled the right ventricle, which was almost obliterated (Fig. 1), and involved the tricuspid valve, causing severe tricuspid stenosis. Endomyocardial biopsy via the right internal jugular vein revealed a thrombus. Tumor marker levels (alpha-1-fetoprotein, CA 19–9, CEA, CA 125) were within normal ranges, as were other laboratory values,
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Josef Besik, M.D., Ph.D., Department of Cardiac Surgery, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 00, Prague 4, Czech Republic. Fax: 00420236052776; E-mail: [email protected]
including the blood count and eosinophils level. However, untreated intermittent hypereosinophilia of unknown origin was the only diagnostic clue in the patient’s medical history. Due to rapid right heart failure progression and hemodynamic deterioration, cardiac surgery was indicated. Surgery was performed through median sternotomy using standard cardiopulmonary bypass with bicaval cannulation without aortic cross clamping and cardioplegic arrest. The right atrium was opened. The tricuspid valve was almost completely attached to the surrounding thrombotic mass and was entirely immobile, with just a small residual opening allowing for atrioventricular communication. The tricuspid valve was excised together with the suspensory apparatus and the mass which filled the entire right ventricle. Tricuspid valve replacement was performed with a 31 mm Carpentier-Edwards Perimount pericardial bioprosthesis (Edwards Lifesciences, Irvine, CA, USA). Histological examination of the mass removed from the right ventricle revealed fibrous, thrombotic and necrotic tissue with residual inflammatory cell infiltration. The patient tolerated the procedure well, and a predischarge TTE showed no pathological findings. The function of the bioprosthesis was normal (gradient 6/ 2 mmHg). The patient was in stable cardiopulmonary condition, placed on Coumadin therapy, and discharged to home care. Four months after the operation, the patient presented again with dyspnea on exertion (NYHA class II) and signs and symptoms of right cardiac failure. Laboratory findings showed a white blood cell count of 13,200 per mm3, with 57% eosinophils (eosinophile count 7,524 per mm3). A diagnosis of idiopathic hypereosinophilic syndrome was confirmed. Medical
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Figure 1. Transthoracic echocardiography showing a pathological mass (white arrow) filling the right ventricle (Ao, aorta; LA, left atrium; LV, left ventricle).
Figure 3. Photograph showing the explanted bioprosthesis viewed from the atrial aspect. The leaflets of the valve are connected by tough fibrotic tissue.
therapy with Imatinib, corticosteroids, digitalis, beta blockers, and diuretics was started. An echocardiogram showed normal systolic function of both ventricles. The leaflets of the tricuspid valve prosthesis were thick (3–4 mm), adhered and exhibited restricted movement. A gradient of 17/8 mmHg was consistent with significant tricuspid stenosis. No abnormal mass, such as a thrombus or vegetation, was present. Despite treatment, one month later (five months after the primary operation), the patient was referred for surgery due to further progression of right-sided heart failure. After performing a resternotomy and connecting the patient to extracorporeal circulation, the right atrium was opened and the degenerated pericardial bioprosthesis was replaced with a 31 mm St Jude Medical Epic porcine bioprosthesis (St Jude Medical, Inc, St Paul, MN, USA). Beating heart surgery was complicated by the development of a third-degree atrioventricular block, requiring the implantation of a permanent pacemaker 18 days after the surgery. The explanted valve (Figs. 2 and 3) and a sample of the surrounding tissue were sent to histology for examination. The removed valve wall contained fibrotic tissue with no
involvement of eosinophils. A sample of the surrounding tissue contained significantly thickened endocardium, which was partially composed of acellular fibrous tissue and fibrous vascularized nonspecific granulation tissue. The adjacent myocardium showed edema and mild fibrosis of the interstitium, with no inflammatory cell infiltration (Fig. 4). The patient tolerated the second operation well. A pre-discharge TTE showed a peak gradient of 11 mmHg, mean gradient of 4 mmHg, and no regurgitation. The patient was discharged in good condition. Coumadin was discontinued and instead she was prescribed lowmolecular-weight heparin (LMWH). In the postoperative period, the patient was regularly monitored for control of peripheral eosinophilia. Hypereosinophilia relapses were successfully treated by temporarily increasing the dose of Imatinib and corticosteroids. Now, over nine years since the second operation, the patient is in stable cardiopulmonary condition and feels well. She is on continued therapy with Imatinib, corticosteroids, digitalis, beta blockers, diuretic, and LMWH. The bioprosthesis in the tricuspid position shows no signs of dysfunction and has stable
Figure 2. Photograph showing the explanted bioprosthesis. Mural thrombi are visible on the side originally facing the right ventricle.
Figure 4. A histology of the excised bioprosthesis (hematoxylin and eosin stain, 20x magnification) shows the morphology of collagenous connective tissue (red) and parietal thrombosis (pink). No eosinophils were found.
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parameters (peak gradient 12 mmHg, mean gradient 4 mmHg).
DISCUSSION Idiopathic hypereosinophilic syndrome is a rarely seen leukoproliferative disorder characterized by unexplained prolonged peripheral eosinophilia with organsystem dysfunction due to eosinophillic infiltration.1 The diagnosis of iHES is based on marked eosinophilia (up to 1,500 cells per mm3) for at least six months while excluding other causes of eosinophilia, which particularly include parasitic infections, hypersensitivity reactions or neoplastic diseases. It may affect practically any organ, and often two or more organs may be affected concurrently.3 Cardiac dysfunction is the most frequent result of end-organ damage (from 54% to 95% of cases)3,4,5 and is the major cause of morbidity and mortality among iHES patients.1 iHES also can affect the nervous system (40–64%), skin (56%), and pulmonary system (40–49%). Less frequently, the gastrointestinal tract, liver, spleen, and ocular system are involved.3,4,5 Idiopathic hypereosinophilic syndrome is more common in men than in women (9:1). Prevalence is most frequent between the 20 and 50 years of age.1 The etiology of iHES is unknown. The most frequently cited causes of iHES are the overproduction of cytokines involved in eosinophilic growth and differentiation, a cytokine disorder featuring enhanced or extended bioactivity, or possible defects in the receptors for these cytokines.1,5 Tissue damage is then caused by the release of various cytotoxic mediators and enzymes from the activated eosinophils. Further contributing to tissue damage are impaired coagulation and increased platelet aggregation, which is also caused by activated eosinophils and eosinophil factors.6 In the heart, eosinophilic infiltration and the production of eosinophil peroxidases usually result in restrictive cardiomyopathy with endocardial fibrosis, mural thrombi, and atrioventricular valve dysfunction.7 Cardiac lesions may occur in either the left or right side or in both. This impairment to the heart was first described by Lo¨ffler in Zurich in 1936 when he documented the cases of two patients with marked sustained peripheral eosinophilia and an unusual type of endomyocardial fibrosis, which is known as Lo¨ffler’s endocarditis.2 Since then, several dozen cases of patients with hypereosinophilia and concurrent cardiac impairment have been described. Its defining characteristic is a finding of endocardial fibrosis, which causes impaired ventricular diastolic relaxation and the presence of intracavitary thrombotic masses, which often significantly reduce ventricular cavity size. Both of these pathological changes result in reduced ventricular filling and the development of forms of congestive heart failure similar to that found in constrictive pericarditis.4,8 The third characteristic of the pathology, damage to the atrioventricular valve, is found in patients where endocardial fibrosis extends to involve the papillary muscles and chordae tendineae, producing mitral or tricuspid insufficiency or stenosis.9
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Treatment of the hypereosinophilic syndrome attempts to limit organ damage by controlling the eosinophil count with aggressive therapy consisting of prednisone, hydroxyurea, interferon alpha, and cytotoxic chemotherapy.10 This medical therapy improves the survival rate to 4% mortality after three years, compared to a 77% mortality within three years without medical therapy.11 Recent studies reported the efficacy of 100 to 400 mg Imatinib daily in HES patients.10,12 Imatinib mesylate (Gleevec, Novartis) is a 2-phenyl-aminopyrimidine-based tyrosine kinase inhibitor. It also inhibits some receptors possibly involved in the pathogenesis of iHES, such as the type III transmembrane receptors KIT or platelet-derived growth factor receptors (PDGFR).10 The reported adverse effects of Imatinib were only mild with a remarkable low incidence of hematological toxicity.12 Surgical experience with valve defects in iHES patients is limited because these defects play a rather minor role in the course and prognosis of the disease when compared to the extent and progression of endomyocardial fibrosis and associated heart failure.9 In 1991, Boustany presented eight cases of iHES patients who underwent mitral valve surgery (seven valve replacements and one mitral valve annuloplasty).13 In 2005, Fuzellier11 published another summary of mitral valve operations in 14 patients, 12 of whom underwent mitral valve replacement and two mitral valve repair. It was shown that mechanical valves in iHES patients have a high incidence of obstructive thrombosis, leading to reoperation and high mortality; bioprosthesis was therefore recommended in cases of mitral valve replacement.11 Tricuspid surgical experience in patients with idiopathic hypereosinophilic syndrome is very limited. Only single cases of tricuspid valve surgery have been published to date (Table 1). Three of ten patients died in a short time after surgery. One patient died six hours after the operation and one died seven months after the operation, both due to right heart failure. One patient died eight months after the operation due to prosthetic valve endocarditis and subsequent sepsis. In most patients (7 cases of 10), the reason for the tricuspid valve procedure was significant regurgitation; stenosis was the dominant pathology in only three cases. Three patients underwent isolated tricuspid valve surgery;14–16 in the other seven cases, a procedure was performed on the mitral valve concurrently with the tricuspid valve surgery. In half of the cases, the tricuspid valve was successfully repaired, while tricuspid valve replacement was required in half of the patients, with four receiving a biological replacement and just one a mechanical replacement.17 This patient’s mitral valve was concurrently replaced with a mechanical prosthesis, but in the postoperative period, he experienced obstructive thrombosis in both mechanical valves and both mechanical valves had to be replaced with biological prostheses (four months after the primary operation). Despite Coumadin therapy, the iHES patients experience thrombosis, even in those with biological valve replacements.11,18 Burstow et al.15 describe the case of a 52-year-old male who developed
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TABLE 1 Tricuspid Valve Surgery in Hypereosinophilic Endocarditis No
Year
Author
Procedure
Tri Path
Surg.
Age
Gen
1 2 3 4 5 6 7 8 9 10
1977 1981 1982 1982 1985 1997 1999 2006 2008 2011
Weyman9 Davies19 Harley17 Harley17 Cameron20 Metzler21 Imoto14 Burstow15 Carnero-Alcazar16 Chu18
MVR þ TVP MVR þ TVR MVR þ TVR MVR þ TVR MVR þ TVR MVP þ TVP TVP TVR TVP MVR þ TVP
Stenosis Regurg. Regurg. Stenosis Regurg. Regurg. Regurg. Stenosis Regurg. Regurg.
Repair Bio Mech Bio Bio Repair Repair Bio Repair Repair
35 36 24 29 45 28 25 52 62 78
F M M M M M M M M F
Follow-Up 6 months, alive 7 months, alive Died* 21 months, alive Died** 20 months, alive 26 days, alive 46 months, alive Died*** 2 months, alive
No ¼ number of case; Tri path ¼ tricuspid valve pathology; Surg. ¼ type of surgery; Gen ¼ gender; MVR ¼ mitral valve replacement; MVP ¼ mitral valve repair; TVR ¼ tricuspid valve replacement; TVP ¼ tricuspid valve repair; regurg. ¼ regurgitation; Bio ¼ bioprosthesis; Mech ¼ mechanical valve; F ¼ female; M ¼ male. * Patient died 8 months after operation—prosthetic valve endocarditis. ** Patient died 7 months after operation—right heart failure. *** Patient died 6 hours after operation—right heart failure.
bioprosthetic dysfunction in the tricuspid position 20 months following implantation. The patient’s condition required reoperation and replacement of the prematurely degenerated bioprosthesis with another bioprosthesis. Significant stenosis developed in this second bioprosthesis in 26 months, when balloon valvuloplasty was performed with a very good immediate effect. In our patient, the bioprosthesis prematurely degenerated with mural thrombosis less than five months from implantation. However, after starting adequate iHES therapy and with regular long-term control of eosinophilia, the patient is in good condition nine years following the second tricuspid valve replacement with no signs of prosthetic dysfunction. Due to the increased risk of thrombosis, tricuspid valve repair should be preferred in iHES patients if technically feasible. In cases where the tricuspid valve must be replaced, preference should be given to a bioprosthesis over a mechanical valve despite the young age of the patient, as mechanical valves are more susceptible to thrombus formation.6,11 Our experience leads us to believe that tricuspid valve replacement with a bioprosthesis in a patient with idiopathic hypereosinophilic syndrome is feasible with good long-term results assuming there is appropriate anticoagulation and regular perioperative and postoperative control of peripheral eosinophilia to minimize the risk of prosthetic valve thrombosis.
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