A woman in her 70s was admitted for acute, painless vision loss in the left eye. Examination showed cherry red spot in the macula and plaque in the nasal vessels, consistent with central retinal artery occlusion. MRI orbits revealed multifocal subclinical acute infarcts in the right middle cerebral artery (MCA) territory and bilateral cerebella. Transthoracic echocardiogram showed calcification of the anterolateral papillary muscle. Further characterisation with cardiac MRI elucidated caseous ‘toothpaste-like’ calcification of the muscle complex. Stroke workup was otherwise unremarkable. The patient underwent hyperbaric treatment with mild improvement. Anticoagulation and surgical intervention were deferred due to known risks and unknown benefit for calcific emboli. The patient was continued on her home dual anti-platelet therapy (DAPT) and discharged with a loop monitor. Caseous calcification of the papillary muscle (CCPM) may be a risk factor for cardioembolic stroke. Further discussions on medical and surgical guidelines for CCPM would be beneficial for stroke prevention.
- Cardiovascular medicine
- Radiology (diagnostics)
- Visual pathway
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Stroke is one of the leading causes of death, and there were 12.2 million incident cases of stroke, 101 million prevalent cases of stroke and 6.55 million deaths from stroke.1 Ischaemic stroke contributed 62.4% of total strokes.1 The underlying aetiology of acute ischaemic stroke is often classified under the Trial of Org 10172 in acute stroke treatment (TOAST) criteria: (1) large-artery atherosclerosis, (2) cardioembolism, (3) small-vessel occlusion, (4) stroke of other determined aetiology and (5) stroke of undetermined aetiology.2 Here, we present, from our knowledge, the only reported case of a patient suffering from suspected cardioembolic strokes secondary to calcific emboli from caseous calcification of the anterolateral papillary muscle (CCPM) of the heart.
A woman in her 70s with medical history notable for hypertension, dyslipidaemia, type 2 diabetes, coronary artery disease with three stents on dual antiplatelet therapy, chronic myelocytic leukemia in remission on bosutinib 400 mg daily and left eye retinal detachment status post repair initially presented to an outside hospital with painless vision loss in the left eye. She denied headache or jaw claudication. She denied tobacco, alcohol or illicit drug use. Non-contrast CT of the head ruled out haemorrhage, but she was outside of the time window for tPA. The patient was transferred to our emergency department (ED) for higher-level care for possible retinal detachment versus central retinal artery occlusion (CRAO). On arrival to the ED, the patient was afebrile and stable.
Clinical examination of the patient revealed a cherry red spot in the macula with macular edema and evidence of white plaque in the nasal vessels coming off the disc. Extraocular movements were intact. Vision in the left eye was limited to only motion detection in the temporal field. Examination was otherwise unremarkable, and National Institutes of Health Stroke Scale (NIHSS) score was 0. Inflammatory markers were mildly elevated. The patient was diagnosed with CRAO. Further workup was initially unremarkable. Coagulation profile was within reference range. Low-density lipoprotein (LDL) was 45 and haemoglobin A1c was 6.2% with a calculated average blood glucose level of 130 mg/dL. CT angiogram showed non-flow-limiting atherosclerosis of the internal carotid artery and normal-appearing aortic arch. Electrocardiogram (EKG) and continuous telemetry did not reveal arrhythmias.
Curiously, MRI orbits with and without contrast revealed multifocal subclinical acute infarcts in the right middle cerebral artery (MCA) territory (figure 1) and bilateral cerebella suggestive of an embolic source of unknown significance (ESUS). Transthoracic echocardiogram with bubble study was unremarkable aside from a calcified anterolateral papillary muscle and mobile calcified echodensity. Subsequent cardiac MRI revealed diffuse caseous ‘toothpaste-like’ calcification of the anterolateral papillary muscle complex (figures 2 and 3).
Acute strokes spanning multiple intracranial vascular territories suggest a cardioembolic aetiology, including atrial fibrillation, left-sided cardiac thrombi, cardiac tumours, valve/muscle vegetations and paradoxical emboli. The patient’s transthoracic echocardiogram and cardiac MRI ruled out cardiac thrombi, tumours and vegetations aside from CCPM. The patient did not have a patent foramen ovale, ruling out paradoxical emboli. Finally, 30-day cardiac rhythm monitoring did not reveal any atrial fibrillation burden, reducing the likelihood of paroxysmal atrial fibrillation. Therefore, CCPM remained high on the differential.
We were sceptical about whether anticoagulation would be beneficial since the emboli were calcific in nature and therefore would not be affected by anticoagulants. Additionally, the heightened risk of bleeds in a patient already on antiplatelets was difficult to justify, with which the patient agreed. Cardiothoracic surgery to replace or decalcify the anterolateral papillary muscle was discussed, but no guidelines currently exist for this kind of procedure. Such an intervention may have required complete replacement of the mitral valve, and notably, surgery for decalcification and/or mitral valve replacement in cases of mitral annular calcification has high mortality and morbidity rates.3 The patient refused surgical intervention due to risk of complications and prolonged recovery process. Ultimately, the decision was made to maintain the patient on dual antiplatelet therapy and outpatient surveillance.
Outcome and follow-up
The patient underwent three rounds of hyperbaric treatment during hospitalisation with mild improvement in left eye vision. She decided against anticoagulation or surgical intervention after discussions with our team. She was sent home with a cardiac event monitor and close follow-up. She was continued on her home aspirin 81 mg daily and rosuvastatin 20 mg daily. Her home ticagrelor 60 mg two times per day was also continued as prescribed by her cardiologist. Loop monitor revealed one episode of non-sustained ventricular tachycardia, but no episodes of paroxysmal atrial fibrillation. Until now, the patient has not had additional clinically significant strokes.
Mitral annular calcification has previously been implicated as a risk factor for stroke.4 However, the rare subset of caseous mitral annular calcification has largely been documented as benign.5 6 More recently, some case reports have reported caseous mitral annular calcification as an independent risk factor for patients’ cardioembolic strokes.7–9 On our review of the literature, no studies or case reports have described CCPM, let alone identified it as a source of cardioembolism to the brain.
We suspected CCPM as the aetiology of our patient’s strokes for multiple reasons. First, the patient’s scattered pattern of infarcts indicated involvement of multiple vascular territories, which pointed to a central source. The patient’s history of hypertension, diabetes, dyslipidaemia and coronary artery disease could all lead to ischaemic stroke but would be unlikely precipitators of multifocal acute infarcts spanning different vascular territories at the same time. Moreover, the patient had been on dual antiplatelet therapy for at least 5 years, and her LDL and A1c were appropriate. There was no flow-limiting stenosis on CT angiogram. No other cardioembolic aetiologies were identified on diagnostic testing. Other aetiologies like hypercoagulability from chronic myelocytic leukaemia were unlikely in the setting of remission and chronic treatment, and the patient’s white blood cell count during admission was within normal limits. Though further workup for an autoimmune aetiology was not pursued, the patient’s antinuclear antibody 2 years prior was normal. The most likely cause of central embolism of ‘white plaque’ to the retinal artery of our patient was calcific emboli from the anterolateral papillary muscle. The underlying cause of CCPM in our patient remains unknown, but it may be multifactorial similar to mitral annular calcification10 and secondary to ageing and the patient’s history of hypertension, dyslipidaemia and coronary artery disease. Serum calcium level was low-normal (8.5–8.9) during hospitalisation with a normal 25-hydroxy vitamin D 7 months prior, and there was no evidence of abnormal calcium-phosphate metabolism or chronic kidney disease.
Caseous calcification of the papillary muscle (CCPM) should be on the differential for cardioembolic aetiologies of ischaemic stroke.
Patients with incidental findings of CCPM should be monitored longitudinally for subclinical infarcts or stroke symptoms, and antiplatelet+statin therapy for primary stroke prevention should be considered.
Cardiac MRI can be a useful tool to characterise echodensities seen on transthoracic echocardiogram (TTE).
Ischemic strokes can be subclinical, and detection of such infarcts with brain MRI will lead to appropriate etiologic classification under the Trial of Org 10172 in acute stroke treatment (TOAST) criteria.
Patient consent for publication
Thank you to Arun Kumar on Fiverr for his excellent cartoon illustration of CCPM in our patient.
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams, and algorithms and critical revision for important intellectual content: RG and SL. The following authors gave final approval of the manuscript: RG and SL.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.