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Purposeful use of multimodality imaging in the diagnosis of caseous mitral annular calcification: a case series report

Purposeful use of multimodality imaging in the diagnosis of caseous mitral annular calcification:... Background: Caseous mitral annular calcification (CMAC) is a rare liquefactive variant of mitral annular calcification (MAC) and superficially mimics a cardiac vegetation or abscess. CMAC is viewed as a benign condition of MAC, while MAC has clinical implications for patients’ lives. Correctly diagnosing CMAC is essential in order to avoid unnecessary interventions, cardiac surgery or even psychological suffering for the patient. Case presentation: We report on 6 patients with suspected intra‑ cardiac masses of the mitral annulus that were referred to our institution for further clarification. A definitive diagnosis of CMAC was achieved by combining echo ‑ cardiography (Echo), cardiac magnetic resonance imaging (MRI) and cardiac computed tomography (CT ) for these patients. Echo assessed the mass itself and possible interactions with the mitral valve. MRI was useful in differentiating the tissue from other benign or malign neoplasms. CT revealed the typical structure of CMAC with a “soft” liquefied centre and an outer capsule with calcification. Conclusion: CMAC is a rare condition, and most clinicians and even radiologists are not familiar with it. CMAC can be mistaken for an intra‑ cardiac tumour, thombus, vegetation, or abscess. Non‑invasive multimodality imaging (i.e. Echo, MRI, and CT ) helps to establish a definitive diagnosis of CMAC and avoid unnecessary interventions especially in uncertain cases. Keywords: Caseous, Mitral annular calcification, Multimodality imaging Background rare (< 1%), often manifests as a local periannular mass, Calcification of the mitral annulus (MAC) is a common and rarely interacts with the function of the mitral valve finding particularly in elderly patients. MAC is associ - [5, 6]. A reliable CMAC diagnosis is thus important in ated with renal and cardiovascular morbidity [1]. In con- order to avoid unnecessary interventions, cardiac sur- trast, caseous mitral annular calcification (CMAC) is gery or even psychological suffering for the patient. Here generally regarded as a benign entity of MAC. However, we present 6 unclear cases of CMAC that were eventu- recent studies reported that CMAC is associated with an ally diagnosed through the use of non-invasive multi- increased risk of stroke and potential conduction abnor- modal imaging techniques such as standard transthoracic malities due to spontaneous fistulisation [2–4]. CMAC is echocardiography (Echo), cardiac magnetic resonance imaging (MRI) and biphasic iodine contrast-enhanced electrocardiographically gated computed tomography *Correspondence: kruno.sveric@caroconnect.de (CT). Department of Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307 Dresden, Germany Full list of author information is available at the end of the article © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sveric et al. BMC Medical Imaging (2022) 22:7 Page 2 of 6 Magnetic resonance imaging findings Case presentation Second, the masses appeared larger in MRI than in Clinical characteristics Echo, but clear differentiation of the CMAC mass from Six out-patients were initially referred to our institution the adjacent myocardium was impaired in the standard for further evaluation of echocardiographically detected steady-state free precision “cine” sequences (Fig.  1C). In intra-cardiac masses at the mitral annulus. The main contrast, T1- and T2 weighted MRI sequences provided clinical characteristics of the patients are summarised in a better depiction of the architecture and morphology of Table  1. Interestingly, the female sex was predominant the mass (Fig.  1D, top left, top right). Furthermore, the (5 of 6) with a median age of 79  years, and with cardio- extent of the mass was more easily distinguished from the vascular risk factors such as arterial hypertension, dys- adjacent myocardium through its hypo-intensity (i.e. low lipidaemia and reduced renal function. Three patients signal intensity) in these sequences. There were no con - had previously suffered ischemic strokes or transitory trast first pass perfusion effects, and no significant late ischemic attacks of unknown etiology. It was thus neces- gadolinium enhancement at the core of the CMAC mass sary to eliminate the possibility of thrombus. In addition, (Fig.  1D, bottom left, bottom right). Absence of vascu- echocardiographic windows were impaired and did not larisation or central necrosis distinguishes it from benign allow a definitive diagnosis of CMAC. In cases 1 and 4, or malign tumours. A description of how multimodality severe calcification of the aortic valve was already sus - imaging can differentiate CMAC from other intracardiac pected by the referring hospital. Careful diagnosis was masses will follow in the discussion section. Additionally, therefore imperative before treatment of severe aortic a thin peripheral ring of late gadolinium enhancement stenosis in these frail patients. Furthermore, two patients indicated the typical CMAC capsule in MRI, but MRI (case 2 and 5) had slightly elevated inflammatory markers had the disadvantage of not disclosing calcified areas as (c-reactive protein 20 and 25 mg/l), but without leukocy- precisely as CT. tosis (4–10 × 10 /l). The one male patient (case 6), how - ever, had lived in a tuberculosis incidence area for several Computed tomography findings years for professional reasons. A tuberculin test was not CT scans revealed the typical demarcation of the hyper- conclusive due to vaccination in childhood. These uncer - dense structure of the “amorphic” and avascular centre tain cases therefore persuaded us to perform a successive without contrast enhancement from the fibrotic capsule three-step approach with Echo, MRI and CT for fur- with small irregular calcifications (Fig. 1E, F). ther clarification. The typical imaging characteristics of CMAC are illustrated as an example in Fig. 1. Further implications of multimodality imaging Nevertheless, the systematic use of these three imag- Echocardiography findings ing modalities gave us not only a definitive diagno - First, CMAC typically appeared in Echo as a mostly sis of CMAC, but also information about important spherical, static and echo-dense (i.e. hyper-echoic) mass “bystander” diagnoses. For example, due to high frailty with smooth borders in the posterior-lateral periannular in cases 1 and 4, CT played a key role in planning the region. It contained one or several central hypo-echoic transcatheter aortic valve replacement for severe aor- areas (Fig.  1A, B). CMAC and the adjacent annular cal- tic stenosis initially diagnosed by Echo (Fig.  2A–C). cification showed some degree of acoustic shadowing, Furthermore, Echo identified an impaired left ven - which prevented precise discrimination of the masses in tricular function with regional anterior hypokinesia the left atrium or the myocardium. Table 1 Main clinical characteristics Case Sex Age (years) BMI GFR (ml/min) LDL level Statin aHT History of MR LVEF (%) (mmol/l) therapy stroke/TIA 1 F 89 24 31 3.1 y y y II 63 2 F 74 29 54 2.6 y y n II 64 3 F 75 23 40 3.4 y y y I–II 40 4 F 91 23 53 4.2 y y y I‑II 65 5 F 79 35 51 2.7 y y n I 61 6 M 62 31 72 3.8 n y n I 65 F, female; M, male; BMI, body mass index; GFR, glomerular filtration rate; LDL, low density lipoprotein; ahT, arterial hypertension; TIA, transitory ischemic attack; MR, mitral valve regurgitation; LVEF, left ventricular ejection fraction; y, yes; n, no S veric et al. BMC Medical Imaging (2022) 22:7 Page 3 of 6 Fig. 1 Exemplary characteristics of CMAC (case 6). Echo: apical long axis view A with the hyper‑ echoic mass (arrow) at the lateral mitral valve annulus with acoustic shadowing; short‑axis view B with a blurred demarcation of the hyper ‑ echoic capsule and hypo‑ echoic core. MRI: cardiac 4‑ chamber view in steady state free precision sequence C with the iso‑intense mass (arrow) to the adjacent myocardium (star), but with a clear hypo‑intense demarcation from intracavitary blood (plus sign); T1‑ weighted sequence with the hypo‑intense mass (arrow) and less intense core in T2‑ weighted sequence (arrow) compared to the myocardium (star) (D; top left and top right); first pass perfusion with low signals of vascularisation compared to myocardium (star) and intraventricular blood (plus sign) (D; bottom left); late gadolinium enhancement with very low signal in the core, but peripheral bright border (arrow) (D; bottom right); CT: precontrast hyperattenuation of the CMAC mass with peripheral calcifications (E) and no accumulation of contrast agent (D). CMAC caseous mitral annular calcification, Echo transthoracic echocardiography, MRI cardiac magnetic resonance imaging, CT cardiac computed tomography in case 3. MRI verified this as a reversible perfusion Discussion defect through stress perfusion sequences with appli- CMAC is a rare variant of the more common MAC [6]. cation of adenosis and led to a successful percutaneous The most challenging aspect of CMAC is its misdiagno - coronary intervention of a relevant stenosis in the left sis as a myocardial abscess, cardiac neoplasm, or even anterior descending artery (Fig.  2D). It is important to thrombus. Echo serves as the first line imaging tool for note that MRI stress sequences were performed only in assessing the mass itself and possible interactions with this one particular case (#3) with suspected myocardial the mitral valve. In straightforward cases, when CMAC ischemia. In general, the first pass effect in MRI is suf - is detected incidentally, Echo identifies the typical char - ficient to assess the vascularisation of the tumour. In acteristics of CMAC: its smooth border; its typical loca- cases 1, 3 and 4, a history of stroke/transitory ischemic tion in the postero-lateral annular region of the mitral attacks was associated with atrial fibrillation without valve; its overall echo-dense structure with hypo-echoic adequate anticoagulation, which we detected by means central areas. Hence, no further work up is needed in of long-term electrocardiograms. It is worth mention- general [5, 7]. Indeed, a myocardial abscess in early stages ing that after comprehensive evaluation of all cases by can be detected by Echo due to its rather non-homoge- the heart team, no patient was referred to cardiac sur- neous appearance, an echo-free space or due to blood gery for CMAC. flow. However, in later stages, when these abscesses Sveric et al. BMC Medical Imaging (2022) 22:7 Page 4 of 6 Fig. 2 Before (A) and after (B) transcatheter aortic valve prothesis (star) for severe aortic stenosis with CMAC (arrow) at the inferior mitral valve annulus in case 4. Echocardiographic 1 year follow‑up visit after transcatheter aortic valve replacement of case 1 (C) with the aortic prosthesis (star) and CMAC mass at posterior mitral valve annulus (star). Percutaneous coronary intervention of the left anterior descending artery (star) and the “shadow” of CMAC (arrow) at the bottom image of case 3 (D). CMAC caseous mitral annular calcification are consolidated and calcified a clear differentiation and lipoma [8, 9]. CMAC, for instance, shows a hypo- from CMAC is very difficult. In uncertain cases, such intense core in T1- and T2-weighted sequences, while as where the acoustic window is impaired, when non- myxoma and lipoma exhibit central hyper-intensities in specific elevation of inflammation markers are present, T2-weighted sequences, due to their mucinous or fatty when anamnesis suggests an underlying malignancy, stroma. Similarly, myocardial abscesses display a central or, as in our case 6, where a history of tuberculosis can- hyper-intensity with a hypo-intense layer, although these not be ruled out, systematic use of MRI or CT is help- characteristics vary by abscess stage and type. Although ful. Furthermore, differentiation from smaller, less mobile myocardial tuberculosis is extremely rare and is supposed myxoma can be cumbersome, since myxoma mostly to manifest in pericardial or prevascular localisations, we appear in the left atrium. Cardiac MRI offers the unique could not rule out a tuberculoma in case 3. In general, opportunity to differentiate cardiac masses based on T1- and T2-weighted MRI sequences reveal non-homo- specific signal intensities, contrast first pass perfusion, geneous hyper-intensities of the tuberculous granuloma, and late gadolinium enhancement (Fig.  1D). T1- and but these imaging features are not specific [10]. A con - T2-weighted sequences are useful in assessing the size trast first pass perfusion sequence uses the same assets as and extent of the cardiac mass, due to its different signal myocardial ischemia detection, and reflects the amount intensity relative to the myocardium [8]. Hypo-, iso- or of vascularisation of the cardiac mass. This specific MRI hyper-intensity indicates the specific fat and water con - method is helpful in differentiating malign from benign tent of the tissue in question. This method allows dif - masses, for instance, between Sarcoma and thrombi [11, ferentiation from various tumours, such as myxoma 12]. CMAC is a mass without vascularisation, hence no S veric et al. BMC Medical Imaging (2022) 22:7 Page 5 of 6 early accumulation of gadolinium is expected. Further- Nevertheless, MRI and CT images of CMAC resemble more, late gadolinium enhancement can be detected the macroscopic descriptions with a toothpaste-like con- more often in malign tumours indicating tissue necrosis, sistency in the centre as an admixture of calcium, fatty but is seldom found in benign neoplasms and very rarely acids, and cholesterol, which is not possible in Echo [6, in thrombi [13]. Typically, CMAC does not show signs 15]. The cases presented here clearly demonstrate the of late gadolinium accumulation, due to the absence of advantage of the systematic utilisation of all three imag- necrotic tissue. Thrombi commonly share the same fea - ing modalities in diagnosing CMAC in uncertain cases. ture in these MRI sequences, differentiation on the basis Due to radiation exposure in CT and long measurement of the characteristics may remain challenging. Myxo- times in MRI, which could be burdensome for patients, mas, for instance, show partial signs of vascularisation we believe the use of CT and MRI should be reserved for or necrosis in MRI, which makes it difficult to further cases where Echo does not provide a definitive CMAC differentiate them from malign masses [12]. If an MRI diagnosis. However, multimodality imaging increasingly is inconclusive further imaging steps may be necessary. plays a major role in the planning of complex interven- Although MRI is helpful in tissue characterisation, it is tional valve treatments, as demonstrated in two of our prone to artefacts during long measurement times caused cases. As our population continues to age, the athero- by inadequate breath holds, cardiac motion and arrhyth- sclerotic burden will increase, while traditional surgical mia. As well as having limited availability, cardiac MRI strategies will become less feasible due to the increas- in our view requires more laborious planning than CT. ing frailty of patients. Some clinical observations thus Cardiac CT easily reveals the typical structure of CMAC need to be mentioned: the majority of our patients with with its avascular “soft” centre, fibrotic capsule and the CMAC were females of advanced age, with pre-existing irregularly calcified rim (Fig.  1E, F) [14]. Tuberculoma are cardiovascular risk factors such as hyperlipidaemia with characterised by a hyper-dense core. Table  2 summaries statin therapy and arterial hypertension with renal dis- the typical characteristics of the more common myxoma, ease. Interestingly, these risk factors are known to be intracardiac thrombus, abscess and tuberculoma with associated with MAC, but are not established in CMAC the three aforementioned imaging modalities. How- [16]. MAC, for instance, is an independent predictor of ever, the pathognomonic depiction of CMAC described myocardial infarction and vascular death, while the clini- above requires pre- and post-contrast scans in CT, which cal implications of CMAC are not fully understood [1, involve significant radiation exposure for the patients. 5]. Further studies need to explore whether CMAC is Table 2 Comparison of typical features of intracardiac masses in multimodality imaging CMAC Myxoma Thrombus Abscess Tuberculoma Localisation/Morphol‑ Posterior MV annulus, 75% LA, interatrial Ubiquitous, mainly LA, Ubiquitous: peri/valvu‑ Mainly pericardial or ogy smooth border septum, smooth smooth lar ≫ myocardial pervascular Echogenicity Overall: hyper, central Hyper, inhomogeneous Inhomogeneous core: hypo Inhomogeneous hyper areas: hypo border: hyper PA: blood flow MRI T1‑ w intensity Hypo Iso Subacute: hypo, Centre: hypo Iso to hyper chronic: hypo T2‑ w intensity Hypo Hyper subacute: hypo, Centre: hypo Mainly iso chronic: hyper FP uptake No Heterogeneous No No Heterogeneous LGE uptake Central: no Heterogeneous No Hyper Heterogeneous Periphery: hyperen‑ Exception: chronic or hancement (“rim”) organised thrombus may show peripheral ring enhancement— DHE CT density Centre: hypo, no Iso, heterogeneous Hypo to iso, no con‑ Centre: hypo, periph‑ Centre: hyper → calcifi‑ contrast enhancement, contrast enhancement trast enhancement ery: contrast enhanced, cation (bone window) periphery: hyper → cal‑ PA: contrast filled cifications (bone window) CMAC, caseous mitral annular calcification; MRI, magnetic resonance imaging; T1-w, T1-weighted; T2-w, T2-weighted; FP, first pass; LGE, late gadolinium enhancement; CT, computed tomography; MV, mitral valve; LA, left atrium; DHE: delayed gadolinium hyperenhancement; PA: pseudoaneurysm Sveric et al. BMC Medical Imaging (2022) 22:7 Page 6 of 6 References the result or the expression of a chronic inflammatory 1. Kohsaka S, Jin Z, Rundek T, Boden‑Albala B, Homma S, Sacco RL, et al. activity with a calcium disorder separate from MAC [17]. Impact of mitral annular calcification on cardiovascular events in a multi‑ Even the pathophysiological mechanism contributing to ethnic community. JACC Cardiovasc Imaging. 2008;1:617–23. https:// doi. org/ 10. 1016/j. jcmg. 2008. 07. 006. the formation of MAC needs further elucidation. This is 2. Dietl CA, Hawthorn CM, Raizada V. Risk of cerebral embolization with all the more true for CMAC, an even rarer entity. caseous calcification of the mitral annulus: review article. Open Cardio ‑ vasc Med J. 2016;10:221–32. 3. Fong LS, McLaughlin AJ, Okiwelu NL, Nordstrand IAJ, Newman M, Pas‑ Conclusion sage J, et al. Surgical management of caseous calcification of the mitral CMAC is a rare condition, and most clinicians and even annulus. Ann Thorac Surg. 2017;104:e291–3. https:// doi. org/ 10. 1016/j. radiologists are unfamiliar with it. CMAC can be mis- athor acsur. 2017. 04. 039. 4. Chevalier B, Reant P, Laffite S, Barandon L. Spontaneous fistulization of a taken for an intra-cardiac tumour, vegetation, or abscess. caseous calcification of the mitral annulus: an exceptional cause of stroke. Non-invasive multimodality imaging (i.e. Echo, MRI, and Eur J Cardiothorac Surg. 2011;39:e184–5. https:// doi. org/ 10. 1016/j. ejcts. CT) in uncertain cases helps establish a definitive diag - 2011. 01. 038. 5. Deluca G, Correale M, Ieva R, Del SB, Gramenzi S, Di Biase M. The nosis of CMAC and avoid unnecessary interventions. incidence and clinical course of caseous calcification of the mitral annulus: a prospective echocardiographic study. J Am Soc Echocardiogr. 2008;21:828–33. https:// doi. org/ 10. 1016/j. echo. 2007. 12. 004. Abbreviations 6. Pomerance A. Pathological and clinical study of calcification of the mitral CMAC: Caseous mitral annular calcification; MAC: Mitral annular calcifica‑ valve ring. J Clin Pathol. 1970;23:354–61. tion; Echo: Echocardiography; MRI: Cardiac magnetic resonance imaging; CT: 7. Harpaz D, Auerbach I, Vered Z, Motro M, Tobar A, Rosenblatt S. Caseous Cardiac computed tomography. calcification of the mitral annulus: a neglected, unrecognized diagnosis. J Am Soc Echocardiogr. 2001;14:825–31. https:// doi. org/ 10. 1067/ mje. 2001. Acknowledgements We are grateful to the patients for their collaboration. 8. Tyebally S, Daniel C, Sanjeev B, Abdallah M, Zeeshan H, Charlotte M, et al. Cardiac tumors: JACC cardiooncology state‑ of‑the ‑art review. JACC Authors’ contributions Cardiooncol. 2020;2:293–311. https:// doi. org/ 10. 1016/J. JACCAO. 2020. 05. KMS and SJ made substantial contributions to the conception and design of the study. IP, EG, KMS and SJ made substantial contributions in the acquisi‑ 9. Esposito A, De Cobelli F, Ironi G, Marra P, Canu T, Mellone R, et al. CMR in tion of clinical and imaging data. KMS, SJ and IP were involved in drafting the assessment of cardiac masses: primary benign tumors. JACC Cardiovasc manuscript and revising it critically. SJ, RTH and AL gave final approval of the Imaging. 2014;7:733–6. https:// doi. org/ 10. 1016/j. jcmg. 2013. 11. 008. version to be published. All authors read and approved the final manuscript. 10. Jagia P, Gulati GS, Sharma S, Goyal NK, Gaikwad S, Saxena A. MRI features of tuberculoma of the right atrial myocardium. Pediatr Radiol. Funding 2004;34:904–7. The authors declare that they have no financial interests. 11. Pazos‑López P, Pozo E, Siqueira ME, García‑Lunar I, Cham M, Jacobi A, et al. Value of CMR for the differential diagnosis of cardiac masses. JACC Availability of data and materials Cardiovasc Imaging. 2014;7:896–905. All data generated or analyzed during this study are included in this published 12. Esposito A, De Cobelli F, Ironi G, Marra P, Canu T, Mellone R, et al. CMR article. in the assessment of cardiac masses: primary malignant tumors. JACC Cardiovasc Imaging. 2014;7:1057–61. https:// doi. org/ 10. 1016/j. jcmg. 2014. 08. 002. Declarations 13. Mousavi N, Cheezum MK, Aghayev A, Padera R, Vita T, Steigner M, et al. Assessment of cardiac masses by cardiac magnetic resonance imag‑ Ethics approval and consent to participate ing: histological correlation and clinical outcomes. J Am Heart Assoc. As this is a case report, no ethics approval was necessary. Written informed 2019;8:1–12. consent was obtained from the patients for publication of this case report and 14. Mayr A, Müller S, Feuchtner G. The spectrum of caseous mitral annulus any accompanying images. calcifications. JACC Case Rep. 2021;3:104–8. 15. Elgendy IY, Conti CR. Caseous calcification of the mitral annulus: a review. Consent for publication Clin Cardiol. 2013;36:E27‑31. Written informed consent was obtained from the patients for publication of 16. Abramowitz Y, Jilaihawi H, Chakravarty T, Mack MJ, Makkar RR. Mitral this case report and any accompanying images. annulus calcification. J Am Coll Cardiol. 2015;66:1934–41. https:// doi. org/ 10. 1016/j. jacc. 2015. 08. 872. Competing interests 17. Massera D, Trivieri MG, Andrews JPM, Sartori S, Abgral R, Chapman AR, The authors declare that they have no competing interests. et al. Disease activity in mitral annular calcification: a multimodality study. Circ Cardiovasc Imaging. 2019;12:1–10. Author details Department of Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307 Dresden, Germany. Publisher’s Note Insitute and Polyclinic for Diagnostic and Interventional Radiology, Dres‑ Springer Nature remains neutral with regard to jurisdictional claims in pub‑ den University Hospital, Technische Universität Dresden, Fetscherstr. 74, lished maps and institutional affiliations. 01307 Dresden, Germany. Received: 22 March 2021 Accepted: 5 December 2021 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png BMC Medical Imaging Springer Journals

Purposeful use of multimodality imaging in the diagnosis of caseous mitral annular calcification: a case series report

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Abstract

Background: Caseous mitral annular calcification (CMAC) is a rare liquefactive variant of mitral annular calcification (MAC) and superficially mimics a cardiac vegetation or abscess. CMAC is viewed as a benign condition of MAC, while MAC has clinical implications for patients’ lives. Correctly diagnosing CMAC is essential in order to avoid unnecessary interventions, cardiac surgery or even psychological suffering for the patient. Case presentation: We report on 6 patients with suspected intra‑ cardiac masses of the mitral annulus that were referred to our institution for further clarification. A definitive diagnosis of CMAC was achieved by combining echo ‑ cardiography (Echo), cardiac magnetic resonance imaging (MRI) and cardiac computed tomography (CT ) for these patients. Echo assessed the mass itself and possible interactions with the mitral valve. MRI was useful in differentiating the tissue from other benign or malign neoplasms. CT revealed the typical structure of CMAC with a “soft” liquefied centre and an outer capsule with calcification. Conclusion: CMAC is a rare condition, and most clinicians and even radiologists are not familiar with it. CMAC can be mistaken for an intra‑ cardiac tumour, thombus, vegetation, or abscess. Non‑invasive multimodality imaging (i.e. Echo, MRI, and CT ) helps to establish a definitive diagnosis of CMAC and avoid unnecessary interventions especially in uncertain cases. Keywords: Caseous, Mitral annular calcification, Multimodality imaging Background rare (< 1%), often manifests as a local periannular mass, Calcification of the mitral annulus (MAC) is a common and rarely interacts with the function of the mitral valve finding particularly in elderly patients. MAC is associ - [5, 6]. A reliable CMAC diagnosis is thus important in ated with renal and cardiovascular morbidity [1]. In con- order to avoid unnecessary interventions, cardiac sur- trast, caseous mitral annular calcification (CMAC) is gery or even psychological suffering for the patient. Here generally regarded as a benign entity of MAC. However, we present 6 unclear cases of CMAC that were eventu- recent studies reported that CMAC is associated with an ally diagnosed through the use of non-invasive multi- increased risk of stroke and potential conduction abnor- modal imaging techniques such as standard transthoracic malities due to spontaneous fistulisation [2–4]. CMAC is echocardiography (Echo), cardiac magnetic resonance imaging (MRI) and biphasic iodine contrast-enhanced electrocardiographically gated computed tomography *Correspondence: kruno.sveric@caroconnect.de (CT). Department of Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307 Dresden, Germany Full list of author information is available at the end of the article © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sveric et al. BMC Medical Imaging (2022) 22:7 Page 2 of 6 Magnetic resonance imaging findings Case presentation Second, the masses appeared larger in MRI than in Clinical characteristics Echo, but clear differentiation of the CMAC mass from Six out-patients were initially referred to our institution the adjacent myocardium was impaired in the standard for further evaluation of echocardiographically detected steady-state free precision “cine” sequences (Fig.  1C). In intra-cardiac masses at the mitral annulus. The main contrast, T1- and T2 weighted MRI sequences provided clinical characteristics of the patients are summarised in a better depiction of the architecture and morphology of Table  1. Interestingly, the female sex was predominant the mass (Fig.  1D, top left, top right). Furthermore, the (5 of 6) with a median age of 79  years, and with cardio- extent of the mass was more easily distinguished from the vascular risk factors such as arterial hypertension, dys- adjacent myocardium through its hypo-intensity (i.e. low lipidaemia and reduced renal function. Three patients signal intensity) in these sequences. There were no con - had previously suffered ischemic strokes or transitory trast first pass perfusion effects, and no significant late ischemic attacks of unknown etiology. It was thus neces- gadolinium enhancement at the core of the CMAC mass sary to eliminate the possibility of thrombus. In addition, (Fig.  1D, bottom left, bottom right). Absence of vascu- echocardiographic windows were impaired and did not larisation or central necrosis distinguishes it from benign allow a definitive diagnosis of CMAC. In cases 1 and 4, or malign tumours. A description of how multimodality severe calcification of the aortic valve was already sus - imaging can differentiate CMAC from other intracardiac pected by the referring hospital. Careful diagnosis was masses will follow in the discussion section. Additionally, therefore imperative before treatment of severe aortic a thin peripheral ring of late gadolinium enhancement stenosis in these frail patients. Furthermore, two patients indicated the typical CMAC capsule in MRI, but MRI (case 2 and 5) had slightly elevated inflammatory markers had the disadvantage of not disclosing calcified areas as (c-reactive protein 20 and 25 mg/l), but without leukocy- precisely as CT. tosis (4–10 × 10 /l). The one male patient (case 6), how - ever, had lived in a tuberculosis incidence area for several Computed tomography findings years for professional reasons. A tuberculin test was not CT scans revealed the typical demarcation of the hyper- conclusive due to vaccination in childhood. These uncer - dense structure of the “amorphic” and avascular centre tain cases therefore persuaded us to perform a successive without contrast enhancement from the fibrotic capsule three-step approach with Echo, MRI and CT for fur- with small irregular calcifications (Fig. 1E, F). ther clarification. The typical imaging characteristics of CMAC are illustrated as an example in Fig. 1. Further implications of multimodality imaging Nevertheless, the systematic use of these three imag- Echocardiography findings ing modalities gave us not only a definitive diagno - First, CMAC typically appeared in Echo as a mostly sis of CMAC, but also information about important spherical, static and echo-dense (i.e. hyper-echoic) mass “bystander” diagnoses. For example, due to high frailty with smooth borders in the posterior-lateral periannular in cases 1 and 4, CT played a key role in planning the region. It contained one or several central hypo-echoic transcatheter aortic valve replacement for severe aor- areas (Fig.  1A, B). CMAC and the adjacent annular cal- tic stenosis initially diagnosed by Echo (Fig.  2A–C). cification showed some degree of acoustic shadowing, Furthermore, Echo identified an impaired left ven - which prevented precise discrimination of the masses in tricular function with regional anterior hypokinesia the left atrium or the myocardium. Table 1 Main clinical characteristics Case Sex Age (years) BMI GFR (ml/min) LDL level Statin aHT History of MR LVEF (%) (mmol/l) therapy stroke/TIA 1 F 89 24 31 3.1 y y y II 63 2 F 74 29 54 2.6 y y n II 64 3 F 75 23 40 3.4 y y y I–II 40 4 F 91 23 53 4.2 y y y I‑II 65 5 F 79 35 51 2.7 y y n I 61 6 M 62 31 72 3.8 n y n I 65 F, female; M, male; BMI, body mass index; GFR, glomerular filtration rate; LDL, low density lipoprotein; ahT, arterial hypertension; TIA, transitory ischemic attack; MR, mitral valve regurgitation; LVEF, left ventricular ejection fraction; y, yes; n, no S veric et al. BMC Medical Imaging (2022) 22:7 Page 3 of 6 Fig. 1 Exemplary characteristics of CMAC (case 6). Echo: apical long axis view A with the hyper‑ echoic mass (arrow) at the lateral mitral valve annulus with acoustic shadowing; short‑axis view B with a blurred demarcation of the hyper ‑ echoic capsule and hypo‑ echoic core. MRI: cardiac 4‑ chamber view in steady state free precision sequence C with the iso‑intense mass (arrow) to the adjacent myocardium (star), but with a clear hypo‑intense demarcation from intracavitary blood (plus sign); T1‑ weighted sequence with the hypo‑intense mass (arrow) and less intense core in T2‑ weighted sequence (arrow) compared to the myocardium (star) (D; top left and top right); first pass perfusion with low signals of vascularisation compared to myocardium (star) and intraventricular blood (plus sign) (D; bottom left); late gadolinium enhancement with very low signal in the core, but peripheral bright border (arrow) (D; bottom right); CT: precontrast hyperattenuation of the CMAC mass with peripheral calcifications (E) and no accumulation of contrast agent (D). CMAC caseous mitral annular calcification, Echo transthoracic echocardiography, MRI cardiac magnetic resonance imaging, CT cardiac computed tomography in case 3. MRI verified this as a reversible perfusion Discussion defect through stress perfusion sequences with appli- CMAC is a rare variant of the more common MAC [6]. cation of adenosis and led to a successful percutaneous The most challenging aspect of CMAC is its misdiagno - coronary intervention of a relevant stenosis in the left sis as a myocardial abscess, cardiac neoplasm, or even anterior descending artery (Fig.  2D). It is important to thrombus. Echo serves as the first line imaging tool for note that MRI stress sequences were performed only in assessing the mass itself and possible interactions with this one particular case (#3) with suspected myocardial the mitral valve. In straightforward cases, when CMAC ischemia. In general, the first pass effect in MRI is suf - is detected incidentally, Echo identifies the typical char - ficient to assess the vascularisation of the tumour. In acteristics of CMAC: its smooth border; its typical loca- cases 1, 3 and 4, a history of stroke/transitory ischemic tion in the postero-lateral annular region of the mitral attacks was associated with atrial fibrillation without valve; its overall echo-dense structure with hypo-echoic adequate anticoagulation, which we detected by means central areas. Hence, no further work up is needed in of long-term electrocardiograms. It is worth mention- general [5, 7]. Indeed, a myocardial abscess in early stages ing that after comprehensive evaluation of all cases by can be detected by Echo due to its rather non-homoge- the heart team, no patient was referred to cardiac sur- neous appearance, an echo-free space or due to blood gery for CMAC. flow. However, in later stages, when these abscesses Sveric et al. BMC Medical Imaging (2022) 22:7 Page 4 of 6 Fig. 2 Before (A) and after (B) transcatheter aortic valve prothesis (star) for severe aortic stenosis with CMAC (arrow) at the inferior mitral valve annulus in case 4. Echocardiographic 1 year follow‑up visit after transcatheter aortic valve replacement of case 1 (C) with the aortic prosthesis (star) and CMAC mass at posterior mitral valve annulus (star). Percutaneous coronary intervention of the left anterior descending artery (star) and the “shadow” of CMAC (arrow) at the bottom image of case 3 (D). CMAC caseous mitral annular calcification are consolidated and calcified a clear differentiation and lipoma [8, 9]. CMAC, for instance, shows a hypo- from CMAC is very difficult. In uncertain cases, such intense core in T1- and T2-weighted sequences, while as where the acoustic window is impaired, when non- myxoma and lipoma exhibit central hyper-intensities in specific elevation of inflammation markers are present, T2-weighted sequences, due to their mucinous or fatty when anamnesis suggests an underlying malignancy, stroma. Similarly, myocardial abscesses display a central or, as in our case 6, where a history of tuberculosis can- hyper-intensity with a hypo-intense layer, although these not be ruled out, systematic use of MRI or CT is help- characteristics vary by abscess stage and type. Although ful. Furthermore, differentiation from smaller, less mobile myocardial tuberculosis is extremely rare and is supposed myxoma can be cumbersome, since myxoma mostly to manifest in pericardial or prevascular localisations, we appear in the left atrium. Cardiac MRI offers the unique could not rule out a tuberculoma in case 3. In general, opportunity to differentiate cardiac masses based on T1- and T2-weighted MRI sequences reveal non-homo- specific signal intensities, contrast first pass perfusion, geneous hyper-intensities of the tuberculous granuloma, and late gadolinium enhancement (Fig.  1D). T1- and but these imaging features are not specific [10]. A con - T2-weighted sequences are useful in assessing the size trast first pass perfusion sequence uses the same assets as and extent of the cardiac mass, due to its different signal myocardial ischemia detection, and reflects the amount intensity relative to the myocardium [8]. Hypo-, iso- or of vascularisation of the cardiac mass. This specific MRI hyper-intensity indicates the specific fat and water con - method is helpful in differentiating malign from benign tent of the tissue in question. This method allows dif - masses, for instance, between Sarcoma and thrombi [11, ferentiation from various tumours, such as myxoma 12]. CMAC is a mass without vascularisation, hence no S veric et al. BMC Medical Imaging (2022) 22:7 Page 5 of 6 early accumulation of gadolinium is expected. Further- Nevertheless, MRI and CT images of CMAC resemble more, late gadolinium enhancement can be detected the macroscopic descriptions with a toothpaste-like con- more often in malign tumours indicating tissue necrosis, sistency in the centre as an admixture of calcium, fatty but is seldom found in benign neoplasms and very rarely acids, and cholesterol, which is not possible in Echo [6, in thrombi [13]. Typically, CMAC does not show signs 15]. The cases presented here clearly demonstrate the of late gadolinium accumulation, due to the absence of advantage of the systematic utilisation of all three imag- necrotic tissue. Thrombi commonly share the same fea - ing modalities in diagnosing CMAC in uncertain cases. ture in these MRI sequences, differentiation on the basis Due to radiation exposure in CT and long measurement of the characteristics may remain challenging. Myxo- times in MRI, which could be burdensome for patients, mas, for instance, show partial signs of vascularisation we believe the use of CT and MRI should be reserved for or necrosis in MRI, which makes it difficult to further cases where Echo does not provide a definitive CMAC differentiate them from malign masses [12]. If an MRI diagnosis. However, multimodality imaging increasingly is inconclusive further imaging steps may be necessary. plays a major role in the planning of complex interven- Although MRI is helpful in tissue characterisation, it is tional valve treatments, as demonstrated in two of our prone to artefacts during long measurement times caused cases. As our population continues to age, the athero- by inadequate breath holds, cardiac motion and arrhyth- sclerotic burden will increase, while traditional surgical mia. As well as having limited availability, cardiac MRI strategies will become less feasible due to the increas- in our view requires more laborious planning than CT. ing frailty of patients. Some clinical observations thus Cardiac CT easily reveals the typical structure of CMAC need to be mentioned: the majority of our patients with with its avascular “soft” centre, fibrotic capsule and the CMAC were females of advanced age, with pre-existing irregularly calcified rim (Fig.  1E, F) [14]. Tuberculoma are cardiovascular risk factors such as hyperlipidaemia with characterised by a hyper-dense core. Table  2 summaries statin therapy and arterial hypertension with renal dis- the typical characteristics of the more common myxoma, ease. Interestingly, these risk factors are known to be intracardiac thrombus, abscess and tuberculoma with associated with MAC, but are not established in CMAC the three aforementioned imaging modalities. How- [16]. MAC, for instance, is an independent predictor of ever, the pathognomonic depiction of CMAC described myocardial infarction and vascular death, while the clini- above requires pre- and post-contrast scans in CT, which cal implications of CMAC are not fully understood [1, involve significant radiation exposure for the patients. 5]. Further studies need to explore whether CMAC is Table 2 Comparison of typical features of intracardiac masses in multimodality imaging CMAC Myxoma Thrombus Abscess Tuberculoma Localisation/Morphol‑ Posterior MV annulus, 75% LA, interatrial Ubiquitous, mainly LA, Ubiquitous: peri/valvu‑ Mainly pericardial or ogy smooth border septum, smooth smooth lar ≫ myocardial pervascular Echogenicity Overall: hyper, central Hyper, inhomogeneous Inhomogeneous core: hypo Inhomogeneous hyper areas: hypo border: hyper PA: blood flow MRI T1‑ w intensity Hypo Iso Subacute: hypo, Centre: hypo Iso to hyper chronic: hypo T2‑ w intensity Hypo Hyper subacute: hypo, Centre: hypo Mainly iso chronic: hyper FP uptake No Heterogeneous No No Heterogeneous LGE uptake Central: no Heterogeneous No Hyper Heterogeneous Periphery: hyperen‑ Exception: chronic or hancement (“rim”) organised thrombus may show peripheral ring enhancement— DHE CT density Centre: hypo, no Iso, heterogeneous Hypo to iso, no con‑ Centre: hypo, periph‑ Centre: hyper → calcifi‑ contrast enhancement, contrast enhancement trast enhancement ery: contrast enhanced, cation (bone window) periphery: hyper → cal‑ PA: contrast filled cifications (bone window) CMAC, caseous mitral annular calcification; MRI, magnetic resonance imaging; T1-w, T1-weighted; T2-w, T2-weighted; FP, first pass; LGE, late gadolinium enhancement; CT, computed tomography; MV, mitral valve; LA, left atrium; DHE: delayed gadolinium hyperenhancement; PA: pseudoaneurysm Sveric et al. BMC Medical Imaging (2022) 22:7 Page 6 of 6 References the result or the expression of a chronic inflammatory 1. Kohsaka S, Jin Z, Rundek T, Boden‑Albala B, Homma S, Sacco RL, et al. activity with a calcium disorder separate from MAC [17]. Impact of mitral annular calcification on cardiovascular events in a multi‑ Even the pathophysiological mechanism contributing to ethnic community. JACC Cardiovasc Imaging. 2008;1:617–23. https:// doi. org/ 10. 1016/j. jcmg. 2008. 07. 006. the formation of MAC needs further elucidation. This is 2. Dietl CA, Hawthorn CM, Raizada V. Risk of cerebral embolization with all the more true for CMAC, an even rarer entity. caseous calcification of the mitral annulus: review article. Open Cardio ‑ vasc Med J. 2016;10:221–32. 3. Fong LS, McLaughlin AJ, Okiwelu NL, Nordstrand IAJ, Newman M, Pas‑ Conclusion sage J, et al. Surgical management of caseous calcification of the mitral CMAC is a rare condition, and most clinicians and even annulus. 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Written informed consent was obtained from the patients for publication of 16. Abramowitz Y, Jilaihawi H, Chakravarty T, Mack MJ, Makkar RR. Mitral this case report and any accompanying images. annulus calcification. J Am Coll Cardiol. 2015;66:1934–41. https:// doi. org/ 10. 1016/j. jacc. 2015. 08. 872. Competing interests 17. Massera D, Trivieri MG, Andrews JPM, Sartori S, Abgral R, Chapman AR, The authors declare that they have no competing interests. et al. Disease activity in mitral annular calcification: a multimodality study. Circ Cardiovasc Imaging. 2019;12:1–10. Author details Department of Internal Medicine and Cardiology, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstr. 76, 01307 Dresden, Germany. Publisher’s Note Insitute and Polyclinic for Diagnostic and Interventional Radiology, Dres‑ Springer Nature remains neutral with regard to jurisdictional claims in pub‑ den University Hospital, Technische Universität Dresden, Fetscherstr. 74, lished maps and institutional affiliations. 01307 Dresden, Germany. Received: 22 March 2021 Accepted: 5 December 2021

Journal

BMC Medical ImagingSpringer Journals

Published: Jan 6, 2022

Keywords: Caseous; Mitral annular calcification; Multimodality imaging

References