Extensive Intramyocardial Calcifications: Value of Multimodality Imaging

Massive myocardial calcification is a very rare finding. Accurate identification and characterization may help the clinicians to determine the etiology and clinical significance. In this case, the diagnostic pathway excluded previous myocardial infarction, myocarditis and calcium-phosphate disorders. A possible dystrophic etiology was considered. There are no standardized imaging features available to classify specific subtypes of intramyocardial calcifications. The relative merits of cardiac computed tomography and magnetic resonance in providing complimentary diagnostic information for calcific myocardial lesions is shown. Knowledge of the potential etiology and their imaging patterns are important to provide a concise and accurate differential diagnosis.

Massive Myocardial Calcification—A Heart Of Stone!

A 71-year-old female was admitted in the emergency room after effort-related syncope. She had past medical history of obesity and hypertension treated with lercanidipine. No relevant family history. Physical examination revealed systolic murmur (grade 2/6). ECG showed sinus rhythm and left bundle brunch block (Supplementary figure). Lab results were unremarkable including troponin I. Transthoracic echocardiography (TTE) revealed moderate left ventricular (LV) hypertrophy [septal thickness 14 mm (normal: 6–9mm)], extensive mitral annulus calcification (MAC) with exuberant myocardial calcification at the level of posterior leaflet that invaded adjacent LV walls, systolic anterior motion of the anterior mitral leaflet causing LV outflow tract (LVOT) obstruction (maximum gradient 34 mmHg) and moderate mitral regurgitation (MR) (Panel A). Exercise echocardiogram provoked LVOT gradient >100mmHg and severe MR. Continuous ECG monitoring during 13 days demonstrated no arrhythmic events. Cardiac CT showed multiple calcifications extending from mitral annulus to LV anterior and lateral walls and cardiac MRI was compatible with caseous MAC (Panels B-F). Coronary angiography showed 50% stenosis of mid left anterior descending artery. Normal thoracic CT and ACE, and negative IGRA excluded sarcoidosis and tuberculosis. Comprehensive study, including calcium metabolism and autoantibodies, excluded metabolic and inflammatory aetiologies of myocardial calcification, which was assumed as dystrophic in the context of MAC. No syncope occurred after bisoprolol 2.5 mg, oral rehydration and discontinuation of lercanidipine. However, rest and exercise TTE failed to show improvement of LVOT gradient or MR and patient remained on NYHA class II-III, despite maximal tolerated dose of bisoprolol (5 mg), being therefore referred to cardiac surgery.

Abstract P475: Microrna-129-5p Rescues Myocardial Fibrosis And Calcification By Targeting Asporin And Sox9 In Cardiac Fibroblasts

Myocardial fibrosis promotes heart failure (HF) progression by impairing myocardial compliance, but also may predispose to myocardial calcification, further impairing cardiac function. Transition of resident cardiac fibroblast (CF) to pro-fibrotic myofibroblasts (MF) and osteogenic cell fates (OF) are key events which are partially controlled by microRNAs (miRs). To discover novel miRs involved in myocardial fibrosis and calcification, we compared online-available microarray datasets of left ventricles (LV) from failing human and mouse hearts. Assessing differentially-expressed miRs known to regulate fibrosis and calcification genes revealed that miR-129-5p is significantly downregulated in HF LV. Bioinformatic target analysis revealed small leucin-rich proteoglycan Asporin (Aspn) and SRY-Box Transcription Factor 9 (Sox9) as two novel miR-129-5p targets upregulated in both mouse and human diseased LV. Thus far, nothing is known about miR-129-5p in cardiac fibrosis and calcification. Additionally, the role of Asporin in myocardial fibrosis and the roles of either Asporin or Sox9 in myocardial calcification remain undiscovered. We show that miR-129-5p is expressed in CF in mouse and human hearts and is downregulated in CF of both HF patients and Angiotensin II (AngII)-injured mice, while Asporin and Sox9 are upregulated in CF of HF LV. In vitro , AngII or transforming growth factor-β downregulated miR-129-5p expression in primary adult mouse CF. Overexpression of miR-129-5p in CF inhibited expression of MF and OF transition markers, reduced migration, collagen production and calcium deposition. We validated Asporin and Sox9 as direct targets of miR-129-5p. Accordingly, silencing of Asporin and Sox9 in CF attenuated molecular and functional characteristics of MF and OF transition. Strikingly, systemic delivery of miR-129-5p mimics in mice directly targets CF and is sufficient to rescue preexisting AngII-induced myocardial fibrosis, calcification, diastolic- and systolic dysfunction. In conclusion, miR-129-5p rescues myocardial fibrosis and calcification by attenuating MF and OF transition via inhibition of Asporin and Sox9 in CF and is a promising therapeutic target.