Resident, Internal Medicine University of Toronto Toronto, Ontario, Canada
Case background: A 59 year old otherwise healthy female with significant smoking history presented with palpitations. The workup was notable for supraventricular tachycardia, which was successfully treated with beta blockade. She underwent computer tomography coronary angiography to rule out concomitant coronary arterial disease that unexpectedly revealed pericardial calcification (Fig 1A). Two years after the index presentation, she continued to be asymptomatic, but underwent a low-dose computed tomography (CT) scan for lung cancer screening. Although there were no suspicious lung lesions, progression of pericardial calcification with definite milk of calcium pericardial effusion was noted (Fig 1B). During routine follow up one year later, the patient reported symptoms of dyspnea, lethargy, fatigue and pedal edema. Physical examination revealed an elevated JVP with positive Kussmaul’s sign. Repeat CT (Figure 2A-F) revealed significant progression of pericardial calcification, in a pattern consistent with milk of calcium (MOC) pericardial constriction. Constrictive physiology was confirmed with both echocardiography and cardiac catheterisation. Figures 1C-F illustrate interventricular dependence by echocardiography, as demonstrated by septal shift with respiration, at least 35% decrease in mitral inflow with inspiration, and reversal of hepatic vein diastolic flow with expiration. Cardiac catheterization demonstrated the classic square-root sign, equalization of end-diastolic pressures (LVEDP-RVEDP < 5mmHg), LV/RV discordance with respiration, RVEDP/RVSP ~50%, and sPAP < 50mmHg, all of which were consistent with constriction. Extensive blood work was negative for causative etiologies such as infection or inflammation.
Management Challenges: The patient remained symptomatic despite medical therapy including diuresis with furosemide. There was no clear clinical or biochemical evidence of inflammatory pericarditis therefore anti-inflammatory agents were deferred. Subsequently, the patient was referred to surgery for pericardiectomy. Although she initially declined surgical management, she developed NYHA class 3 symptoms over the subsequent 18 months and underwent successful pericardiectomy. Intra-operatively, a large amount of milky colloidal suspension was noted to fill the pericardium, along with heavily calcified plaque adherent to the epicardium on the posterior aspect of the heart. The colloidal fluid was aspirated and pericardium resected. Pathologic examination revealed thickening and fibrosis of the pericardium with extensive calcification and focal chronic inflammation. Intraoperative bacterial cultures were negative for an infectious etiology. She recovered well post-operatively and the patient reported improved symptoms immediately after and 6 weeks following the surgery.
Discussion MOC is often an incidental finding, typically detected with CT, ultrasound or x-ray. Whilst MOC elsewhere in the body is frequently described as a benign condition, it may present with symptoms due to the space occupying calcification compressing the surrounding tissues. It does not usually involve cardiac structures and is typically reported in cystic structures, particularly the kidneys and breasts. One retrospective study showed that sedimented calcifications consistent with MOC are seen in approximately 4% of symptomatic women undergoing mammography (1). Moreover, MOC may be identified in the kidney and has been misdiagnosed as renal calculi (2). The pathophysiology of milk of calcium deposition and the involvement of particular organs remain poorly understood. Previous reports show a possible association of MOC with therapeutic radiation (3), while a contemporary postmortem report of a MOC pericardial effusion with constriction leading to right heart failure identified group G β-hemolytic streptococci as the likely causative factor (4). In two other recent reports of MOC pericardial effusions, the etiology was deemed idiopathic (5, 6). Pericardiectomy is the mainstay of definitive treatment for constriction. This has been demonstrated in prior reports and was also the case for our patient. However, further investigation is required to understand the mechanisms, pathophysiology, and possible treatment modalities of milk of calcium with cardiac involvement.
Figures Fig 1) CT scan of calcific sedimentation on ventricular free wall at presentation (A) and two years later (B). Apical 4 Chamber View Echocardiogram, showing septal interdependence (C). Marked hepatic vein diastolic flow reversal with expiration (D). Cardiac catheterization tracing showing square root sign and equalization of diastolic pressure within all four chambers of the heart.
Fig 2) A-B. Short-axis oblique and 4-chamber images from the initial CT demonstrating pericardial calcification overlying the anterior and lateral walls of the left ventricle (LV). Note the calcification of visceral and parietal pericardium (230-240HU) with lower density pericardial space (110-150HU) overlying the lateral wall of the LV, consistent with a small loculated milk of calcium effusion. D-E. Short-axis and 4-chamber images 5 years later demonstrating new calcification of visceral and parietal pericardium with a loculated milk of calcium effusion partially encasing the basal right ventricle (RV). There is less relaxation of the basal half of the RV free wall compared to the previous scan (both were 75% RR cardiac phase acquisitions) and there has been interval evolution of the small milk of calcium effusion into more dense pericardial calcification overlying the lateral wall of the left ventricle. C. Axial non-contrast CT image demonstrating the difference in density between the visceral and parietal pericardium (solid arrow) measuring 450-550HU and the pericardial space (*) containing the milk of calcium measuring 200-230HU. F. Volume rendered technique reconstruction demonstrating dense pericardial calcification (*) overlying the basal third of the left ventricle.
