Case presented by: Michael Arad1 and Orly Goitein2,
Leviev Heart Institute1 and Department of Diagnostic Imaging2, Sheba Medical Center and Tel Aviv University, Israel
KK, a 36 years old male of Yamanite Jewish origin was evaluated for anginal chest pain. He had a history of heavy smoking and family history of coronary artery disease in his mother aged 60. His brother died suddenly at age 26 during a soccer game and his maternal uncle had hypertrophic cardiomyopathy (Fig 1).
The ECG showed sinus rhythm, P mitrale, deep S waves in V3 and pronounced R waves in V4, profound ST depression and deep T wave inversion in V3-6, without criteria for LVH (Fig 2A). An echo-Doppler study showed left ventricular dimension of 58 mm, interventricular septum 13 mm, posterior wall 8 mm, left atrial dimension 47 mm/ left atrial area 31 cm2, LVEF 55% with no prominent regional dysfunction. There was a mobile mass occupying the apical region and protruding up to the level of papillary muscles. Blood flow was demonstrated between the lesion and the left ventricular free wall (Fig. 2 B,C,D). There was a grade II diastolic dysfunction and normal right ventricular size and function.
The patient underwent cardiac CT angiography which showed normal coronary arteries. Tissue density of the left ventricular mass was compatible with a thrombus (Fig. 3 A, B). Cardiac CMR (3C) indicated thrombus with blood in its periphery (i.e. between the mass and the wall). Delayed gadolinium enhanced images (3D) show a hypointense thrombus with surrounding hyperintense signal which might be compatible fibrosis and some revascularization within the thrombus, suggestive of an organized thrombus.
No autopsy data was available in the late brother. The mother had a normal echo. A maternal uncle (1 of 13 siblings) suffered from recurrent syncope, was diagnosed with hypertrophic cardiomyopathy and underwent ICD implantation. He had P mitrale and ST changes on ECG (Fig. 4A), septal thickness of 22 mm (4B), LVEF 65%, biatrial enlargement (4C) and a grade III diastolic dysfunction (4D). Left ventricular outflow tract obstruction could be evoked on Valsalva. There was no history of cardiomyopathy in the extended family, although only a few were evaluated as recommended by HCM guidelines (Fig. 1).
The proband (KK) was treated by anticoagulation and bisoprolol and became asymptomatic. There was no blood eosinophilia, evidence of systemic inflammation or troponin elevation. A right ventricular endomyocardial biopsy showed focal interstitial fibrosis with minimal hypertrophic changes, presence of fibrin and blood clot but no eosinophils or inflammatory cells.
The presented case of KK is compatible with endomyocardial fibrosis in association with thrombus formation. Other clinical features and family history are suggestive of familial hypertrophic cardiomyopathy. Importantly, there was no evidence of systemic or myocardial inflammation and no eosinophilia (Fig. 5). The Congo Red stain was negative.
The inheritance could be autosomal dominant with incomplete penetrance or X-linked. We ruled out Fabry disease but otherwise the family was not interested in gene testing. Serologic testing for collagen vascular diseases were negative but a search for hypercoagulable state in KK was diagnostic for antiphospholipid syndrome [PTT 53 sec (24-38) due to prolongation of circulating-anticoagulant sensitive PTT; elevated anticardiolipin (IgG 95, IgM 35 u/ml) and anti- b2 glycoprotein antibodies (IgG 25, IgM 190; all normal ranges 0-15].
Endomyocardial fibrosis was described by Davies as an independent disease entity and got a name obliterative cardiomyopathy (1). It is often associated with hypereosinophilia and thrombus formation resulting from endocardial inflammation and injury by the infiltrating eosinophils (2). Importantly, the resulting scarring may manifest after disappearance of eosinophilia as “isolated” endomyocadial fibrosis, what is not uncommon in the African population (3,4). A similar pattern of subendocardial stiffening and fibrosis is described in hearts affected by connective vascular disorders (5). These conditions may be uneasy to differentiate from endocardial fibroelastosis: a thickening of the
endocardium by layers of collagenous and elastic fibers not involving the sub-endocardial myocardium, which was described in association with multiple conditions including infections, congenital malformations and cardiomyopathies (6). The ESC classification of cardiomyopathies included all these entities within the clinical spectrum of restrictive cardiomyopathy (7).
Endomyocardial fibrosis is not a characteristic feature of hypertrophic cardiomyopathy. Apical scarring and thrombus do occur in apical cardiomyopathy with aneurysm formation. However, a layer of fibrotic tissue restricted to the endocardium is rather an exception and was reported only in a few isolated cases (8,9). Importantly, a pattern of widespread subendocardial delayed gadolinium, enhancement on CMR should prompt testing for cardiac amyloidosis (10). Needless to say, such a pathology further impairs the diastolic filling leading to severe heart failure.
The presented family seems to manifest as hypertrophic cardiomyopathy with prominent diastolic dysfunction (see Fig. 4, echo-Doppler from the uncle in the case presentation). Such phenotypic expression comprising hypertrophic and restrictive features, occurs with certain sarcomere protein mutations, primarily troponin I and myosin and sometimes troponin T (11). However, left ventricular thrombus formation is not part of the clinical spectrum of this cardiomyopathy in the absence of apical aneurysm. An additional factor should therefore be looked for. In our case KK had hypertrophic cardiomyopathy and antiphospholipid syndrome.
Addendum: KK is receiving an anticoagulant therapy which shall be continued lifelong due to underlying hypercoagulable state. An ICD was implanted due to HCM with family history of sudden death.
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