Caseous calcification of the mitral annulus associated with stroke: Report of two cases

revue neurologique 171 (2015) 157–160

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Neurovascular disease

Caseous calcification of the mitral annulus associated with stroke: Report of two cases Calcification case´euse de l’anneau mitral associe´e a` des infarctus ce´re´braux : rapport de deux cas S. Sagnier a,b, M. Poli a, M. Oysel-Mestre c, O. Corneloup d, S. Debruxelles a, P. Renou a, F. Rouanet a, I. Sibon a,b,* a

Unite´ neuro-vasculaire, CHU de Bordeaux, place Ame´lie Raba-Le´on, 33076 Bordeaux cedex, France Unite´ neuro-vasculaire, poˆle de neurosciences cliniques, hoˆpital Pellegrin, universite´ Bordeaux Segalen, CHU de Bordeaux, place Ame´lie Raba-Le´on, 33000 Bordeaux, France c Antenne cardiologique, CHU de Bordeaux, place Ame´lie Raba-Le´on, 33076 Bordeaux cedex, France d Radiologie, CHU de Bordeaux, place Ame´lie Raba-Le´on, 33076 Bordeaux cedex, France b

info article

abstract

Article history:

Objective. – Caseous calcification of the mitral annulus (CCAM) is a rare complication of

Received 21 April 2014

mitral annulus calcification (MAC). Whether CCAM should be considered as a cardiac source

Received in revised form

of stroke or a simple marker of atherosclerosis remains a matter of debate.

6 June 2014

Method. – Herein, we report two patients with stroke and CCAM.

Accepted 18 July 2014

Results. – The first one was associated with extensive aortic arch atheroma, while CCAM

Available online 21 January 2015

was the only potential cause in the second case. Transthoracic echocardiography was normal in both cases and CCAM was diagnosed on transesophageal echocardiography.

Keywords:

Conclusion. – These observations suggest that CCAM should be added to the list of minor

Mitral annulus calcification

cardioembolic sources of stroke but also requires a perfect control of vascular risk

Caseous calcification

factors. # 2014 Elsevier Masson SAS. All rights reserved.

Stroke Vascular risk factors Atherosclerosis

Mots cle´s :

r e´ s u m e´ Objectif. – La calcification case´euse de l’anneau mitral (CCAM) est une complication rare des

Calcification de l’anneau mitral

calcifications mitrales. Le fait que la CCAM devrait eˆtre conside´re´e comme une source

Calcification case´euse

d’infarctus ce´re´bral (IC) cardioembolique ou comme un simple marqueur d’athe´roscle´rose

Infarctus ce´re´bral

reste encore un sujet de discussion.

Facteurs de risque cardiovasculaire

Me´thode. – Nous rapportons le cas de deux patients avec IC et CCAM.

Athe´roscle´rose

Re´sultats. – Le premier cas e´tait associe´ a` une importante athe´romatose de la crosse aortique, alors que la CCAM e´tait la seule cause potentielle de l’IC dans le second cas.

* Corresponding author. E-mail address: [email protected] (I. Sibon). http://dx.doi.org/10.1016/j.neurol.2014.07.019 0035-3787/# 2014 Elsevier Masson SAS. All rights reserved.

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revue neurologique 171 (2015) 157–160

L’e´chocardiographie transthoracique e´tait normale dans les deux cas et le diagnostic de CCAM a e´te´ fait sur l’e´chocardiographie transœsophagienne. Conclusion. – Ces observations sugge`rent que la CCAM devrait eˆtre ajoute´e a` la liste des causes mineures d’IC cardioemboliques, mais ne´cessite aussi un controˆle parfait des facteurs de risque cardio-vasculaires. # 2014 Elsevier Masson SAS. Tous droits re´serve´s.

1.

Introduction

Cardioembolic strokes represent 20 to 30% of ischemic stroke according to TOAST classification (Trial of Org 10172 in Acute Stroke Treatment) [1]. The most frequent cause is atrial fibrillation. Many other high risk cardioembolic sources have been reported such as intracardiac thrombus, myxoma, endocarditis, recent myocardial infarct or mechanical prosthetic valve [2]. Besides these major sources, several diseases such as aortic arch atheroma or patent foramen ovale have been reported as potential minor causes due to their low or uncertain embolic risk. Mitral annulus calcification (MAC) is a more controversial cause of stroke, but its caseous calcification (CCAM) is thought to be associated with an increased risk of cerebral embolism [3,4]. In echocardiographic studies, MAC is reported to occur in 10.6% of the population [5], and CCAM, rare complication of MAC, is reported in less than 3% of the cases on pathological studies [6]. Herein, we report two patients with ischemic stroke and CCAM and discuss the potential mechanisms linking these two diseases.

2.

Case report

2.1.

Case 1

A 66-year-old patient was referred to our stoke unit for left hemiplegia, left facial palsy and dysarthria. He had a previous history of smoking, hypertension, hypercholesterolemia, chronic bronchitis, and colon cancer in remission. Brain magnetic resonance imaging (MRI) showed a cerebral infarct of the right middle cerebral artery (MCA) territory. At admission, the National Institute Health Stroke Scale (NIHSS) was 18 and he got intravenous thrombolysis. Serum biological evaluations were normal (LDL cholesterol = 0.75 g/L, HDL cholesterol = 0.57 g/L, and HbA1c = 6.3%). Computed tomography (CT) angiography of the cervical arteries was normal as well as echocardiogram (EKG), 24 hours EKC-holter, and transthoracic echocardiography (TTE). The transesophageal echocardiography (TEE) found calcification of the mitral annulus with a heterogeneous round formation of nine millimeters diameter on the atrial face of the anterior mitral annulus. TEE also showed aortic atheroma with lipid plaques of nine millimeters thickness on the descending thoracic aorta, and four millimeters on the aortic arch, without mobile element. Cardiac-CT showed an extensive calcification of the inferior and external portions of the mitral annulus with caseous necrosis aspect (Fig. 1). CCAM and aortic arch atheroma were considered as potential stroke mechanism.

A conservative treatment with a dual antiplatelet therapy and increased control of vascular risk factors was decided associated to a follow-up using TEE.

2.2.

Case 2

A 78-year-old patient was referred to our stroke unit for right hemiplegia and aphasia. He had a previous history of monoclonal gammopathy of undetermined significance and hepatic artery aneurysm. He had no vascular risk factors. Brain MRI showed recent multifocal stroke suggesting a cardiac cause. CT-angiography of extra- and intracranial arteries did not demonstrate significant atheroma. The patient was treated by intravenous thrombolysis but did not improve. The TTE and 24 hours EKG-holter were normal. TEE showed an ovoid mobile hyperechogenic mass measuring 11  7 millimeters, hanging on the ventricular face of the anterior mitral annulus. The cardiac-CT ruled out the diagnostic of tumor and concluded to a caseous necrosis at the insertion of anterior mitral annulus. As it remained the only potential stroke mechanism at the end of an extensive work-up, a surgical treatment was performed which confirmed the diagnosis.

3.

Discussion

MAC is a current finding in the elderly, with a female predominance. MAC is often observed in the context of diffuse atherosclerosis, chronic renal failure with hemodialysis, and abnormal calcium metabolism [3,7,8]. CCAM has to be differentiated from heart valve masses such as tumor, abscess, or thrombi because it implies different treatment and prognosis. In most cases, the echocardiographic presentation is a large echodense mass with central areas of echolucencies, located predominantly in the posterior region between left atrium and left ventricle [3,9]. Our cases emphasize the fact that TTE, which was normal in our two patients, may not be sufficient to confirm the diagnosis and that a TEE or a multimodality imaging approach should be performed in these cases. The benefit of TEE over TTE in the diagnosis work-up of stroke mechanism has been extensively evaluated, allowing the identification of a potential cardiac source in 40% [10,11] and modifying treatment strategies in about 30% of the cases [12]. Beside TEE, other heart imaging techniques such as cardiac-CT or Cardiac Magnetic Resonance (CMR) imaging can add valuable information to improve the characterization of mitral valve masses. Cardiac-CT can demonstrate a high density mass with foci of calcification, while CMR might be the method of reference for the assessment of CCAM, showing the

revue neurologique 171 (2015) 157–160

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Fig. 1 – Cardiac-CT demonstrating extensive calcifications of the mitral annulus with caseous necrosis aspect.

central cavitation on T2 weighted imaging and inversion recovery sequences, and a typical peripheral ring-like enhancement [13,14]. The potential pathogenic role of MAC and CCAM as a source of embolic stroke has been suggested by several authors but remains controversial [15–18]. For example, in an elderly cohort, Benjamin et al. [16] reported that subjects with MAC had a double risk of stroke, after adjustment for main vascular risk factors, while no association was found by Boon et al. on a large series of 657 patients with MAC [19]. Moreover, it remains a debate about the fact that MAC is an independent cause of stroke or a simple marker of atherosclerosis, such as in our first observation. According to this observation, Adler et al. [20] showed that MAC was significantly associated with aortic atheroma  5 mm and/or with protruding, mobile or ulcerated plaque. MAC and CCAM are also reported to be associated with hypertension and coronary heart disease [5]. In addition, the structural changes leading to CCAM could increase the risk of stroke as suggested by Harpaz et al. [21] who reported in a small sample of 19 patients that 26% had history of cerebrovascular events.

The best therapeutic strategy to manage CCAM has not yet been established. Using a conservative approach based on a reinforcement of vascular risk factors control, Harpaz et al. reported 3 deaths among 19 patients after a mean follow-up of 3.8  2.4 years, none of them being related to CCAM [21]. Although the natural history of CCAM is not perfectly known, it seems to be a dynamic process with potential evolution to simple annular calcification, then emphasizing the place of a conservative management [3,22]. The resolution of CCAM could be explained by a gradual liquefaction and dissolution of the central core with microscopic leaks of the calcific external wall without evident clinical consequences. However, it is still not established whether this resolution is spontaneous or secondary to modification of serum calcium or cholesterol level [3,22]. Conversely, complications such as severe mitral regurgitation or stenosis, and conduction disorders have also been reported, which suggest that a regular follow-up remains necessary to identify patients needing surgical procedure [3,5]. CMR appears to be an excellent imaging modality for the follow-up of CCAM progression, as it allows a good tissue characterization [4].

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In the absence of vascular risk factors or widespread atherosclerosis and when a cardiac embolism is strongly suspected based on radiological criteria such as in our second case, CCAM can be considered as the most probable cause of stroke, and surgery is considered as the treatment of choice [5,15,23]. In these cases, stroke could be the consequence of embolization of small calcification, of thrombus from ulceration of the surface, or fistulization of the caseous necrosis in the lumen of left atrium or ventricle [5,23]. There is no consensus on the best therapy, and some authors also suggest anticoagulant therapy, in particular when there is communication between CCAM and systemic circulation [15,24]. This therapeutic option is interesting as it is reported that MAC and CCAM could be associated with atrial fibrillation [5].

4.

Conclusion

CCAM is a rare complication of MAC which must be differentiated from other cardiac valve masses. It requires conservative or interventional management depending on the extent of the atherosclerotic disease and the probability of direct involvement in stroke mechanism.

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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