Abstract
Background
Cardiac calcifications are a rare consequence of end-stage renal failure and hyperparathyroidism.
Case Summary
A 35-year-old man with no prior medical history was admitted to our institution with sudden blindness in his right eye and severe renal failure. Ophthalmologic evaluation revealed central retinal artery occlusion with arterial calcifications. End-stage chronic renal failure was diagnosed. A positron emission tomography-computed tomography (CT) and a Tc-99m multiplex ion beam imaging scintigraphy confirmed hyperparathyroidism. Transthoracic echocardiography, magnetic resonance imaging, and cardiac CT identified significant myocardial calcifications and restrictive cardiomyopathy caused by hyperparathyroidism and renal failure. Management included dialysis and parathyroidectomy.
Discussion
This is the first human report to assess cardiac calcifications associated with hyperparathyroidism and end-stage renal failure with a strong correlation between transthoracic echocardiography, magnetic resonance imaging, and cardiac CT.
Take-Home Message
Calcium-phosphorus metabolic disorders and renal failure contribute to multiple systemic complications, including vascular disease, cardiomyopathy, and atrial fibrillation.
Key Words: computed tomography, disorders of calcium metabolism, echocardiography
Visual Summary
History of Presentation
A 35-year-old man was admitted to our institution with sudden blindness in his right eye, accompanied by vomiting, tremors, and right knee pain. He also reported the appearance of multiple indurated and white lesions in the inguinal folds, armpits, and scrotum (Figure 1).
Take-Home Messages
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This case highlights a severe complication of hyperparathyroidism in end-stage renal failure, characterized by extensive cardiac calcifications and central retinal artery occlusion due to calcifications and cardioembolism.
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It is the first case to assess cardiac calcifications using multimodal cardiac imaging, demonstrating strong correlation among transthoracic echocardiography, cardiac magnetic resonance, and cardiac photon-counting detector computed tomography.
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Calcium-phosphorus metabolic disorders and renal failure contribute to multiple systemic complications, including dermatologic lesions, vascular disease, cardiomyopathy, atrial fibrillation, and gout.
Figure 1.
Photograph of the Scrotal Skin Showing Ulceration and Induration
Past Medical History
The patient had no known medical history. However, his son was diagnosed with kidney atrophy. He lived with his wife and son and worked as a mechanic. He had been a daily tobacco smoker since the age of 17 but denied using any other toxic substances.
Investigations
Laboratory test results revealed an inflammatory syndrome, with a C-reactive protein level of 95 mg/L (normal <5 mg/L) and leukocytosis of 35 × 109/L (normal range: 4-10 × 109/L). The patient also had anemia, with a hemoglobin level of 8 g/dL (normal range: 13-18 g/dL). Natriuresis was impaired, and hypercalcemia was noted at 2.68 mmol/L (normal range: 2.20-2.60 mmol/L). Severe acute renal failure was present, with a creatinine level of 95 mg/L (normal <10 mg/L), selective proteinuria (2-3 g/d), but no microscopic hematuria.
The patient presented with sudden, painless blindness in the right eye. Examination of the anterior segment was unremarkable except for mydriasis, whereas fundus evaluation revealed optic fiber whitening (Figure 2A). Optical coherence tomography confirmed hyper-reflectivity of the optic fibers and deep capillary plexus, indicative of calcifications (Figure 2B). Fluorescein angiography identified central retinal artery occlusion (CRAO) as the underlying cause. The left eye showed no abnormalities. During hospitalization, the patient developed atrial fibrillation, suggesting a potential cardioembolic origin for the CRAO, leading to the initiation of anticoagulation therapy.
Figure 2.
Ophthalmic Evaluation
Photograph of the right fundus (A) and correlated macular optical coherence tomography (B). Calcifications of retinal nerve fibers (hyper-reflectivity, white stars) scattered around the optic nerve head, and corresponding posterior hyporeflectivity (white lines). Only a small portion of normal retina remains (white arrow), surrounded by atrophic retina with deep capillary plexus calcifications (dotted line).
Neuroimaging, including a magnetic resonance imaging of the brain and supra-aortic trunks, was normal, with no evidence of carotid stenosis. An abdominal-pelvic computed tomography (CT) revealed significant ureteral hydronephrosis and right kidney atrophy, with no detectable obstructing stones.
Regarding hypercalcemia, parathyroid hormone (PTH) levels were markedly elevated at 3,800 ng/L (normal <60 ng/L). A positron emission tomography-CT scan identified hyperfunctional retrothyroid nodules consistent with hyperparathyroidism (HPT), along with acute pancreatitis and brown tumors as secondary manifestations. Multiplex ion beam imaging scintigraphy localized 3 hyperactive parathyroid foci (Figure 3).
Figure 3.
MIBI Scintigraphy
The MIBI scintigraphy found 3 foci and a parathyroid adenoma. The parathyroid adenoma is described in transversal, sagittal, and coronal views (bottom row, white stars). MIBI = multiplex ion beam imaging.
A transthoracic echocardiography revealed restrictive cardiomyopathy with extensive myocardial calcifications (Figure 4, Video 1, Video 2, Video 3), affecting multiple left ventricular segments, including the basal inferior, mid-inferior, posteromedial papillary muscle, basal anteroseptal, basal anterolateral, basal and mid-inferolateral, and basal anteroseptal regions. These calcified segments exhibited total akinesia. The apical segments had fewer calcifications, with relatively preserved myocardial function. The mitral valve apparatus remained unaffected. The left ventricular ejection fraction was estimated at 45%. The aortic valve displayed calcification and remodeling but without stenosis. The left atrium volume index was increased (36 mL/m2) with atrial wall calcification. However, the left ventricle showed no signs of dilation or hypertrophy. Mitral inflow analysis revealed an E/A ratio of 1.7, with a lateral e′ wave of 7 cm/s, septal e′ wave of 5 cm/s, and an E/e′ ratio of 15. The right ventricle was dilated (end-diastolic diameter of 35 mm in the parasternal long axis) and exhibited moderate hypokinesis. Tricuspid annular plane systolic excursion measured 15 mm, and S-wave Doppler tissue imaging was 8 cm/s. Calcifications were also present on the anterior and free walls of the right ventricle, as well as the infundibular wall. The right atrium area was increased (24 cm2). In addition, a circumferential pericardial effusion was noted but with no hemodynamic impact. The inferior vena cava was thin, with no signs of respiratory flow variability.
Figure 4.
Transthoracic Echocardiography
Parasternal long axis views in 2 and 3 dimensions showed pericardial effusion (white stars) next to the left ventricle in the basal posterior segment, measured at 12 mm and extensive calcifications in the basal posterior and basal anteroseptal segments (A, B). Parasternal short axis view showed calcifications in the right ventricle free wall and extensive calcifications in most of basal segments in the left ventricle (C). Apical 4-chamber view also revealed calcifications of the base of the left ventricle.
A cardiac CT and cardiac magnetic resonance were performed to evaluate myocardial calcifications. The cardiac CT, performed on a first-generation dual-source photon-counting detector CT (PCCT) machine, confirmed calcifications in the free wall of the right ventricle, the mitral subvalvular apparatus, the papillary muscles, and the tricuspid valve (Figure 5). Notably, the Agatston calcium score was 796 Hounsfield units. The left anterior descending and second diagonal arteries exhibited mild calcified stenosis <25%, whereas the circumflex artery showed no stenosis. Calcifications were present in the mid and basal segments of both ventricles, including papillary muscles.
Figure 5.
Cardiac CT on Photon-Counting Detector CT Machine
Unenhanced (left column), coronary CT angiography (middle column), and 5-minute iodine delayed enhancement (right column). Short axis view (top row), 2-chamber view (middle row), and 4-chamber view (bottom row). The orange arrowheads indicate basal myocardial calcifications. The red stars indicate calcifications of right ventricle free wall. Calcifications were also present in subvalvular apparatus and papillary muscles (yellow arrowheads) and tricuspid valve (blue arrows). CT = computed tomography.
Iodine map derived from spectral PCCT series, along with late gadolinium enhancement on cardiac magnetic resonance, demonstrated delayed myocardial enhancement corresponding to areas of replacement fibrosis, affecting 33% of the left ventricular mass (Figure 6). Cardiac magnetic resonance also revealed global hypokinesia, with a left ventricular ejection fraction of 49% and a global longitudinal strain of −13.3%. T2 values were within normal limits and myocardial inversion time was normal.
Figure 6.
Cardiac Imaging on With Photon-Counting CT and Cardiac MRI
Iodine map derived from photon counting computed tomography (CT) spectral data (left column) and late gadolinium enhancement with cardiac magnetic resonance (middle column) in basal short axis (top row), apical short axis (middle row), and 3-chamber views (bottom row). Curvilinear reconstruction of the left anterior descending artery (right column) from coronary CT angiography. In basal myocardial calcifications (orange arrowheads), we pointed out both iodine and gadolinium late enhancement (red stars), with good correspondence between the 2 cross-sectional imaging modalities and corresponding to replacement fibrosis. The absence of obstructive coronary artery disease in the left anterior descending artery excluded ischemic cause for apical delayed enhancement.
The absence of obstructive lesions in the left anterior descending artery ruled out an ischemic cause for the apical contrast enhancement. PCCT demonstrated an increased extracellular volume, consistent with fibrotic scars on late gadolinium enhancement (Figure 7).
Figure 7.
Extracellular Volume Calculation From Spectral Series Acquired With Photon Counting CT
Reconstruction in basal short axis (top left), apical short axis (top right), and 3-chamber views (bottom left) with extracellular volume color map overlay. Extracellular volume displayed as a bull's eye map (bottom right). Ranges where extracellular volume was increased are green, yellow, and orange. They are consistent with fibrosing impairment on delayed enhancement series. CT = computed tomography; ECV = extracellular volume.
Management
The diagnosis of calcinosis secondary to renal failure and HPT was established in relation to the patient's dermatologic lesions with a biopsy, corresponding to skin calcifications (Figure 8). Management included initial rehydration, treatment of hypercalcemia, and control of the inflammatory syndrome, which stabilized creatinine levels at 55 mg/L. The underlying condition was identified as malformative uropathy, with genetic testing yielding negative results. Proteinuria was attributed to focal segmental glomerulosclerosis, and immunologic assessments, complement levels, and viral serologies were unremarkable. The initial inflammatory syndrome and gonalgia were attributed to a gout attack.
Figure 8.
Histopathologic Section of the Skin
Dermal foci of calcium deposition (asterisks). Hematoxylin-eosin-safran, original magnification ×200.
Dialysis options were discussed with the patient, leading to the creation of an arteriovenous fistula. Cinacalcet was initiated, and the patient underwent subtotal parathyroidectomy, including excision of a parathyroid adenoma. Before anesthesia, PTH levels were 2,300 ng/L, decreasing to 260 ng/L within 20 minutes after excision.
The patient is currently undergoing dialysis 3 times per week via the fistula and has been placed on the kidney transplant waiting list. After the management of renal and parathyroid dysfunction, the dermatologic lesions resolved completely. Heart transplantation was discussed with a multidisciplinary heart team but was contraindicated because of obliterative arterial disease in the lower limbs. The patient is now followed by heart failure specialists.
Discussion
Primary HPT is the most common endocrinopathy in postmenopausal women, with a prevalence of 1%. It is characterized by elevated calcium levels with high PTH levels or with normal calcium dosage with inappropriate PTH levels. Its complications include bone loss due to osteoclast activation, leading to osteopenia and an increased risk of fractures, particularly in cortical bone regions. A rare but severe bone manifestation is Von Recklinghausen's fibrocystic osteitis (brown tumors), which can cause pathologic fractures and characteristic subperiosteal erosions on radiographs.
Patients with hypercalcemia and HPT may experience asthenia and myalgias, exacerbated by hypophosphatemia. Kidney stones, often bilateral, are common. Although most cases of primary HPT are sporadic, genetic forms are linked to MEN1 or RET mutations.
Secondary HPT is caused by chronic renal failure and is characterized by elevated PTH with normal calcium levels. Tertiary HPT is the result of chronic renal failure with empowerment of parathyroid glands. Secondary and tertiary HPT share the same complications with primary HPT related to calcium disorders.
HPT is associated with cardiovascular risks such as myocardial infarctions, arrhythmias, and atherosclerosis, though the underlying mechanisms remain unclear.1 Osteopenia and primary HPT are also independent risk factors for valvular calcifications.2 In patients with severe chronic kidney disease, metastatic calcifications are well documented, with reports of pericardial effusion and restrictive cardiomyopathy patients with pericardial effusion and myocardial calcifications with restrictive cardiopathy.3,4 Experimental studies in rats have demonstrated cardiac myocyte calcifications in subepicardial regions due to primary HPT.5
This case represents the first human report of myocardial calcifications associated with HPT. It is difficult to assess the difference between primary and tertiary HPT for our patient, but kidney malformation appears to be the initial issue. However, distinguishing whether these calcifications resulted from HPT or severe renal failure is challenging, as both conditions were treated simultaneously. A follow-up cardiac CT one year after diagnosis will allow for lesion reassessment.
Conclusions
Cardiac calcifications in the setting of end-stage renal failure and HPT are rare, with restrictive cardiomyopathy being a significant consequence. Atrial fibrillation, CRAO, obliterative arterial disease, and calcium-phosphorus metabolic disturbances are common complications in such patients.
Visual Summary.
Overview of Hospital Stays and Medical Care
| Date | Events |
|---|---|
| First hospitalization (month 1) | Hospitalization for sudden blindness in his right eye and severe acute renal failure. Fundus examination and OCT showed CRAO and calcifications. MIBI scintigraphy and PET-CT showed hyperparathyroidism loci. Patient had subtotal parathyroidectomy. A biopsy of the dermatologic lesion was performed and revealed dermal foci of calcium deposition. TTE showed extensive myocardial calcifications. Delayed enhancement and myocardial calcifications were assessed with spectral PCCT with a good correspondence with cardiac magnetic resonance regarding myocardial enhancement. PCCT assessed the increase in extracellular volume that had not been measured by cardiac magnetic resonance (no T1 mapping series). |
| Second hospitalization and follow-up (6 mo to 1 y) | Second hospitalization in intensive care unit for pulmonary edema due to less ultrafiltration during hemodialysis and restrictive cardiopathy. Heart transplantation was discussed with a multidisciplinary heart team, but the patient was contraindicated due to obliterative arterial disease in the lower limbs. The patient is now on the waiting list for kidney transplant. |
CRAO = central retinal artery occlusion; MIBI = multiplex ion beam imaging; OCT = optical coherence tomography; PCCT = photon-counting detector computed tomography; PET-CT = positron emission tomography-computed tomography; TTE = transthoracic echocardiography.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Apical 4-Chamber View in TTE
Transthoracic echocardiography in the apical 4-chamber view showing extensive cardiac calcifications in the left atrium and the basal anterolateral and septal inferior regions with preserved myocardial function.
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Transthoracic echocardiography in the parasternal long axis showing calcifications in posterior and anteroseptal segments. Note the pericardial effusion next to posterior segments.
Parasternal Short Axis View in TTE
Transthoracic echocardiography in the parasternal short axis showing calcifications of papillary muscles. Calcifications are also present in the right ventricle.
References
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Associated Data
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Supplementary Materials
Apical 4-Chamber View in TTE
Transthoracic echocardiography in the apical 4-chamber view showing extensive cardiac calcifications in the left atrium and the basal anterolateral and septal inferior regions with preserved myocardial function.
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Transthoracic echocardiography in the parasternal long axis showing calcifications in posterior and anteroseptal segments. Note the pericardial effusion next to posterior segments.
Parasternal Short Axis View in TTE
Transthoracic echocardiography in the parasternal short axis showing calcifications of papillary muscles. Calcifications are also present in the right ventricle.