A previously unreported case of a complex congenital cardiac anomaly consisting of coronary and valvular angiodysplasia, complicated by an eosinophilic endomyocardial disease, is described. The disorder presented clinically with congestive heart failure, which was characterized by evidence of floating masses causing severe pulmonary stenosis and dysfunction of the mitral and aortic valves. Symptoms of cardiac failure disappeared following pulmonary valve replacement and steroid therapy. (CHEST 2004; 126:1700-1703)
Key words: cardiac angiodysplasia; eosinophilic endomyocarditis; pulmonary stenosis
Abbreviations: LV = left ventricle, ventricular
Ectasia of the epicardial coronary arteries is a rare abnormality, which is sometimes associated with diffuse dysplastic lesions of intramural vessels and intraventricular sshunting.1,2 Its association with hugely dilated vessels in cardiac valve tissue resulting in images similar to those of extensive vegetation has never been described before. Such a complex vascular malformation may remain unrecognized in the absence of cardiac symptoms and can be complicated by superimposed inflamination/infection.
We report an unusual case of diffuse cardiac angiodysplasia that was detected by the appearance of heart failure related to eosinophilic endomyocarditis, with vasculitis of dysplastie vessels causing pulmonary, aortic, and mitral valve disease.
CASE REPORT
A 60-year-old woman was admitted to the hospital because of dyspnea with minimal effort (New York Heart Association class III). In childhood, a harsh systolic murmur at the upper left sternal border and a mild systolic mnrmnr at the apex radiating toward the axilla were detected. From early adulthood, the patient started to experience episodes of bronchitis and reduced effort tolerance. For this reason, at 40 years of age the patient underwent a cardiologic assessment, including an echocardiograni, which showed mild mitral regurgitation and moderate pulmonary stenosis. Because of the absence of rheumatic disease or systemic infection in the clinical history, the valve lesions were interpreted as being due to a congenital anomaly. Dyspnea with exertion worsened 6 months before the hospital admission in association with the onset of atrial fibrillation. She had neither risk factors for coronary artery disease nor a history of asthma, allergic rhinitis, or systemic disease.
Physical examination revealed congestive heart failure, atrial fibrillation, a 4/6 systolic murmur, and pulsatile hepatomegaly. A chest radiograph showed pulmonary congestion and prominence of the cardiac border. The ECG showed atrial fibrillation (mean heart rate, 75 beats/min) and a right bundle branch block. Hematologic tests showed moderate eosinophilia (600 10^sup 6^ eosinophils/L) with partially degranulated eosinophils. The coproculture was negative for parasitic infections. Echocardiography showed left and right ventricular hypertrophy (interventricular septum, 16 mm; left ventricular [LV] posterior free wall, 13 mm; right ventricular free wall, 22 mm), LV dilation (LV end-diastolic diameter, 61 mm; LV end- systolic diameter, 50 mm), and LV dysfunction (LV ejection traction, 35%). The right ventricular ejection traction was 40%, and a tricuspid regurgitation ratio of 2+/4+ (in which 2+ is the grade of regurgitation and 4+ is the maximal degree of observed severity, rated on a 4-point scale as follows: 1+, minimal; 2+ , mild; 3+ , moderate; 4+ , severe) was present. The pulmonary valve was characterized by the presence of large floating masses resulting in severe valvular stenosis (maximum gradient, 55 mm Hg). An additional mass was adherent to the atrial surface of the anterior mitral valve leaflet, causing a mild stenosis and moderate regurgitation. The aortic valve showed multiple vegetations, causing mild stenosis. Both atria were dilated. The presence of multiple valvular masses first suggested infectious endocarditis, but the results of serial hemocultures and serologic tests, including the assessment of antineutrophil cytoplasmic antibodies, were negative for that condition.
Because of the severe pulmonary stenosis, surgical replacement of the pulmonary valve was planned. Consequently, the patient underwent coronary angiography that revealed a diffuse ectasia of the coronary tree with tortuous vessels. The diameters of the ectasic vessels were its follows: left niainstem, 12 mm; left anterior descending artery, 9 mm; left circumflex artery, 8.4 mm; and right coronary artery, 8.7 mm. Additionally, this angiodysplastic lesion involved intramural arteries supplying a network of teleangectasic vessels shunting into the ventricular cavities (Fig 1).
Surgical findings showed a pulmonary valve that was characterised by the presence of abundant “cauliflower-shaped whitish tissue of elastic consistence (Fig 2, top), obstructing the right ventricular outflow tract. The abnormal valve was replaced with a prosthetic valve (Carpentier-Edwards 25), and the right ventricular outflow tract was reconstructed using a bovine pericardial patch. The abnormal tissue present at the infundibular level was partially excised, and several endomyocardial biopsy samples were obtained from the right ventricle.
FIGURE 1. Left coronary angiography (top) and right coronary angiography (bottomn) showing ectasic vessels spreading into a diffuse network of channels that shunt into the left and right ventricular cavity.
Histologic examination of the pulmonary valve revealed the presence of large, dysplastic vessels, with an artery-like composition of the wall consisting of endothelial, thick medial, and adventitial layers (Fig 2, bottom). Diffuse eosinophilic infiltrates of abnormal vessels were found, together with foci of vessel wall necrosis. The endomyocardial tissue was characterized by the presence of extensive inflammatory infiltrates, mainly represented by degranulated eosinophils and focally associated with necrosis of the adjacent myocytes (Fig 3). Neither epithelioid cells nor giant cells, sparsely distributed or organized in granulomas, were present.
FIGURE 2. Surgical view (top) of the stenotic pulmonary valve showing whitish floating masses that at histology (bottom) consist of large, dysplastic vessels surrounded by dense inflammatory infiltrates (hematoxylin-eosin, original 20).
A diagnosis of eosinophilic endomyocardial disease was made, superimposed on cardiac angiodysplasia involving not only the epicardial but also the intramural coronary arteries and valvular vessels. No abnormal vascularization of other organs was obseized on a total body angio-CT scan. Because of eosinophilic endomyocarditis and vasculitis, the patient was treated with steroids (prednisone, 1 mg/kg/daily for 1 month followed by 0.33 mg/kg daily for 6 months). Within 7 days, the peripheral blood eosinophil count dropped to 80 10^sup 6^ cells/L and degranulation disappeared. After 2 weeks of treatment, the patient’s clinical condition improved remarkably, resulting in a change in New York Heart Association class III to class I. At the 6-month follow-up, echocardiography showed a reduction of LV end-diastolic diameter from 61 to 55 mm, an increase in ejection fraction from 35 to 55%, and the normalization of right ventricular contractility. Mitral and tricuspid regurgitation improved from 2+ to 1+, respectively.
DISCUSSION
Congenital heart diseases are well-known predisposing factors for inflammatory cardiac pathologies. The incidence of inflammation/ infection of the cardiac valves, in particular infectious endocarditis, is about 10 times move frequent in adults with congenital cardiac abnormalities than that in the healthy population.3 We have reported the case of a patient with eosinophilic endomyocarditis superimposed on a rare vascular malformation of the intravalvular cardiac vessels, as well as that of the intramural and epicardial vessels.
FIGURE 3. Specimen from the right ventricular biopsy showing eosinophilic infiltrates associated with the necrosis of adjacent myocytes (hematoxylin-eosin, original 250).
Coronary artery ectasia is a rare congenital or acquired malformation (eg, atherosclerotic or inflammatory malformation), accounting for up to 4.5% of coronary angiograms.1,2 It is associated with a variable prognosis depending on the extension and severity of vessel dilation, and is classified into four major types (the Markis classification).4 In our patient, the extensive intramural network of vessels shunting into the ventricular cavities in the absence of coronary sclerosis or occlusions suggested a congenital origin for the coronary lesion. Moreover, the involvement of the vessels of the cardiac valves, which are usually well- represented in the human fetus and undergo progressive regression from early age to adulthood,5 is highly suggestive of the presence of a complex vascular malformation that, because of the negative systemic CT scan findings, was confined to the heart. The malformation resulted in a thickening of the ventricular walls due to intramural vessel dilation and in masses of vascularized tissue in the cardiac valves, which are more evident in the pulmonary valve, where it led to an outflow obstruction. The valvular lesions were present several years before the hospital admission, since a diagnosis ofcongenital valvular anomaly was made in early adulthood. Nevertheless, it is only when an eosinophilic endomyocardial disease was superimposed on the congenital vascular malformation that the pulmonary stenosis progressed to a critical stage, and the patient s symptoms worsened with the onset of atrial fibrillation and heart failure. The eosinophilic inflammation was detected in the surgically removed pulmonary valve, in right ventricular tissue from the outflow tract, and in right ventricular endomyocardial biopsy specimens.
The cause of the eosinophilia in our patient was considered to be idiopathic, since no parasitic infection or neoplastic disorder was detected, and there was no history of asthma or allergic rhinitis, which is suggestive of Churg-Strauss syndrome. Moreover, the absence of the characteristic histologic markers (ie, granulomas, epithelioid cells, and giant cells) and the negative results of tests for antineutrophil cytoplasinic antibodies ruled out Churg- Strauss syndrome, which also has been described in nonasthmatic cases.6 The disease was still in the active necrotic phase, as documented by the intense endomyocarditis and vasculitis also involving the abnormal intramyocardial and intravalvular vessels. Due to the potential release of cationic proteins from degranulating eosinophils, the use of steroids along with surgical intervention was necessary in order to avert such major cardiovascular complications as malignant arrhythmias, or the recurrence of valvular dysfunction leading to unbeatable heart failure.
CONCLUSION
Cardiac angiodysplasia invoking epicardial, intramural, and intravalvular vessels is a rare abnormality that is susceptible to inflammatory complications, which, in turn, lead to multiple valvular dysfunction and heart failure. The patients may benefit from combined surgical and medical therapy.
* From the Cardio-Thoracic and Vascular Department (Drs. >Chimenti, La Penna, Pieroni, Alfieri, and Maseri) and Pathology Department (Dr. San Vito) San Raffaele Hospital, Milan, Italy; and the Cardiology Department (Dr. Frustaci), Catholic University, Rome, Italy.
REFERENCES
1 Frustaci A, Caldarulo M, Pagliari G, et al. Coronary angiodysplasia causing a left ventricular shunt and myocardial ischemia. Am Heart J 1993; 125:889-891
2 Frustaci A, Chimenti C, Pieroni M, et al. Coronary angiodysplasia of the epicardial and intramural vessels. Chest 2000; 118:1511-1513
3 Thilen U. Infective endocarditis in adults with congenital heart disease. Curr Infect Dis Rep 2003; 5:300-306
4 Markis JE, Joffe CD, Cohn PF, et al. Clinical significance of coronary arterial ectasia. Am J Cardiol 1976; 37:217-222
5 Duran CMG, Cunning AJ. The vascularization of the heart valves: a comparative study. Cardiovasc Res 1968; 3:290-296
6 Val-Bernal JF, Mayorga M, Garcia-Alberdi E, et al. Churg- Strauss syndrome and sudden cardiac death. Cardiovasc Pathol 2003; 12:94-97
Cristina Chimenti, MD, PhD; Elisabetta La Penna, MD; Maurizio Pieroni, MD; Francesca San Vito, MD; Ottavio Alfieri, MD; Attilio Maseri, MD; and Andrea Frustaci, MD
Manuscript received December 11, 2003; revision accepted June 3, 2004.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).
Correspondence to: Andrea Frustaci, MD, Cardiology Department, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy; e-mail: [email protected]
Copyright American College of Chest Physicians Nov 2004
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