FISH法により弁組織にエンテロウイルスgenomeを証明しえた腱索断裂による僧帽弁閉鎖不全を伴う急性心筋炎の1例

Detection of Enteroviral RNA in Myocardial/Valvular Tissue by Fluorescent in situ Hybridization in Acute Mitral Regurgitation due to Ruptured Chordae Tendineae:A case report

　症例は10カ月，男児．2日前より微熱と頻回の下痢があり，急激な呼吸困難を主訴に来院．心尖部のgrade 3／6汎収縮期雑音と胸部X線写真上肺うっ血像を呈した．心エコー図にて僧帽弁後尖の腱索断裂と僧帽弁閉鎖不全（MR），右心負荷所見を認めた．内科治療に反応せず，肺水腫，右心不全増悪したため，僧帽弁腱索再建術施行．術後MRが再増悪したため＃19St．Jude Medical弁にて僧帽弁置換術を施行した．しかし，心機能低下が著明で人工心肺離脱できず術後7日目に永眠した．光顕組織所見では弁組織に軽度の細胞浸潤と粘液様変性を認めた．心筋，僧帽弁，乳頭筋組織をfiuorescent in situ hybridization（FISH）法で検索した結果，エンテロウイルス（EV）genomeに対するhybridization signalが認められた．原因不明の僧帽弁腱索断裂やMRの一部はEV感染が誘因となりうると考えられた．僧帽弁腱索断裂症例でウイルスとの関連を示唆する報告は稀と思われ，今後検索されるべきであると考えられた．

A 10-month-old boy was admitted to our emergency room with complaints of progressive dyspnea and cyanosis. He was completely healthy until 2 days before admission when he began to suffer a slight fever and frequent diarrhea. On physical examination there was a grade 3/6 holosystolic murmur at the apex and left axilla. Bacterial culture and virus isolation were negative. Laboratory findings included the following: WBC 18,900/μ1, CRP 3.6mg/d1. GOT 61 IU/ l. LDH 1.126 IU/l. CK 376 IU/l, CK-MB 37 ILI/ l. Chest X-ray demonstrated evidence of severe pulmonary edema and normal cardiac silhouette with a cardiothoracic rate of 47%. 2-D echocardiography revealed severe mitral regurgitation due to rupture of the chordae tendineae (CT) of the posterior mitral valve (MV) leaflet. Despite intensive therapy for respiratory failure and cardiac dysfunction, the patient's condition rapidly deteriorat-ed. The patient then underwent reconstruction of the ruptured CT and valvuloplasty on the 3rd hospital day. Operative findings revealed that three CT attached to the posterior leaflet of the MV were completely reputur-ed. Microscopic findings revealed a small focus of infiltration of inflammatory cells and myxomatous degeneration in MV. However, severe mitral regurgita-tion and the state of low cardiac output occured againafter surgery. Replacement of the reconstructed CT and MV with ♯19 St. Jude Medical prosthesis was undertaken. Postoperative cardiac function was insufficient, and the patient expired 7 days after surgery. Autopsy findings demonstrated intercellular edema and inflammatory cell infiltration in the myocardium of the right ventricle (RV) and the left ventricle (LV). Fluo-rescent in situ hybridization (FISH) for detection of enteroviral genome was performed in cardiac samples using a biotin-tailed DNA probe produced by RT-PCR from 154bp of the non-coding region of coxsackie virus type B1 cDNA, which is specific for a variety of entero-viruses (EV). As a result, positive hybridization signals for EV RNA were clearly observed in several samples obtained from the LV through the left atrium (LA) including the mitral valve leaflet. papillary muscle, CT, the junction of the LA and the LV. RV free wall, LV free wall, and the endocardial cushion including the upper part of the interventricular septum.

We conclude that rupture of CT of the MV may occur in EV myocarditis. In this patient. FISH technique was useful for detection of virus genome in the myocardium and valvular apparatus. Molecular study should be performed in patients with sudden onset of ruptured CT of the MV with unexplained etiology.