A 69-year-old lady was admitted to the acute medical unit with a several-month history of progressive, exertional breathlessness and atypical chest pain. Cardiac risk factors were hypertension, hyperlipidaemia, and a positive family history of ischaemic heart disease. Drug therapy on admission was simvastatin and amlodipine.
Clinical examination revealed a grade 3 pansystolic murmur radiating to the apex, with no signs of cardiac failure, organomegaly, or lymphadenopathy. The pulse was regular at 81 bpm, BP was 119/90 mmHg, and oxygen saturations were 100% on room air. EKG demonstrated sinus rhythm with fixed, lateral T-wave inversion and ST depression. Serial troponin-Is were 44, 44, and 31 ng/L (normal range: 0-14). Haematology and blood biochemistry were normal including d-dimer, liver function tests, and serum amylase. Chest X-ray demonstrated normal lung fields; however, subtle intracardiac calcification within the cardiac silhouette was visible and comparable to a radiograph in 2015.
A transthoracic echocardiogram (echo) demonstrated mobile valve leaflets with an echo-bright structure in the region of the posterior mitral annulus suggestive of calcification. However, views were limited due to poor echogenicity with incomplete visualisation of the myocardium. A transoesophageal echocardiogram (TOE) revealed a heavily calcified mitral annulus but no mitral stenosis. A bidirectional jet of moderate mitral regurgitation (MR) was noted secondary to extensive mitral annular calcification (MAC) with tethering of the leaflet tips, particularly the anterior mitral valve leaflet. No other valvular heart disease was present, and the left ventricle (LV) retained good contractility throughout with overall normal function.
A CT coronary angiogram (CTCA) (Siemens' SOMATOM Definition Flash CT) showed extensive MAC which infiltrated the left ventricular myocardium resulting in widespread intramyocardial calcification, predominantly in the septum and anterior wall and also in the apex and apical lateral wall (Figure 1). Maximal septal LV wall thickness measured 28 mm and similarly around the infiltrative lesions. The calcified lesions were heterogenous in appearance and extended from the mitral annulus. The external layer of the lesions was calcific, whilst the internal portion was of a heterogenous lower density signal, suggesting caseation. The myocardium contracted normally around the lesions with the estimated ejection fraction of 57%. Calcification of the coronary arteries was apparent with moderate mid-left anterior descending artery (LAD) disease and moderate stenosis of the proximal first diagonal vessel. Thoracic CT screening for extracardiac calcification and carcinoma was unremarkable.
Due to the extent of the intramyocardial calcification, we sought to determine the aetiology and screen for metabolic disease. Serum calcium, phosphate, and eGFR were normal. PTH levels were slightly raised at 8.6 pmol/L (normal range: 1.3-7.3); the vitamin D level was low at 21 nmol/L (normal range: 100-200) indicating vitamin D deficiency. Hb was 119 g/L (normal: 120-160) with negative haemolytic and haematinic screenings. Lipid profile revealed a triglyceride level of 5.0 mmol/L (normal: 0.12-2.10) and HDL of 0.99 mmol/L (normal: 1.2-1.8) with the total cholesterol measuring 5.7 mmol/L. There was an isolated raised bilirubin of 38 microm/L (range: 0-17), but the direct Coombs test and haptoglobin levels did not suggest haemolytic anaemia. Autoantibody screens (immunoglobulins, ANA, ANCA, dsDNA) were negative. Serum iron levels were slightly low; however, the total iron binding capacity was normal. Serum ACE levels were 24 U/L (normal: 8-52). Abdominal ultrasound confirmed fatty liver infiltration. Tuberculosis exposure was excluded through careful history taking and supported with a negative acid-fast bacilli sputum sample.
Although still experiencing exertional breathlessness, the patient's symptoms improved with low-dose furosemide, and given the presence of coronary artery disease on CTCA, she was discharged with dual antiplatelet therapy added to her current medication regimen.
Cardiac MRI was performed (Figure 2), and similar to the CT, this showed extensive calcification extending into the myocardium from the mitral valve annulus, evidenced by the absent signal on T1- and T2-weighted imaging. The lesions enhanced on late gadolinium imaging suggesting the presence of an extracellular matrix within the calcium, but they were not encased entirely by calcium and were in communication with the surrounding myocardium. The findings were consistent with an aggressive caseating, calcific process extending into the left ventricular myocardium from the mitral valve annulus. The infiltrated myocardium was thickened with reduced contractility, whilst the noninfiltrated myocardium contracted well and compensated to maintain an overall normal left ventricular ejection fraction.
Coronary angiography showed moderate mid and distal LAD disease, in addition to severe distal posterior descending artery (PDA) disease (Figure 3); this was not felt sufficient to explain the aetiology of her breathlessness.
PET CT was requested to further examine the calcified lesions within the myocardium and evaluate for metastatic calcific phenomenon. This scan demonstrated no abnormal uptake nor metabolic activity outside of the heart, therefore providing reassurance for our patient with exclusion of metastatic infiltrative disease. Interestingly, there was some evidence of metabolic activity around the calcified lesions within the heart; however, it is uncertain whether this represents an active disease process or the chronic inflammatory process described in the caseating tissue.
Given her symptomatic improvement and normal left ventricular function, ongoing surveillance was arranged with interval scanning.