A 22-year-old Woman with Ischemic Stroke and Left Ventricular Dysfunction
Shikhar Agarwal MD MPH CPH, Cardiology Fellow, Cleveland Clinic
A 22-year-old female was transferred to the Cleveland Clinic from an outside hospital for evaluation of acute ischemic stroke. She has presented to an outside hospital two days prior with acute onset numbness and tingling of bilateral upper extremities and mild expressive aphasia.
Figure 1: Axial section of the computed tomography
of the brain demonstrating areas of subacute infarction
in the left fronto-parietal area.
Past Medical History
Her past medical history was significant for migraines with aura. Six months prior to her current presentation, the patient had a transient episode of forgetfulness and confusion for four hours and one month ago the patient had reported an episode of numbness and tingling of her left lower extremity lasting three hours. She did not seek medical attention for these episodes.
Initial physical examination at the outside hospital
On initial presentation, the patient had a blood pressure of 128/84 mm Hg, heart rate of 75 beats per minute and respiratory rate of 16 breaths per minute saturating at 98%, while breathing ambient air. Her lungs were clear to auscultation. Cardiac auscultation did not reveal any murmurs or gallops. Abdomen was non-tender, non-distended without any hepatosplenomegaly. Skin examination was significant for three circular macules ranging 1-3 mm on the right hand. Neurological examination was significant for focal weakness in the distal left upper extremity.
Hospital course prior to presentation to Cleveland Clinic
Computed tomography of the brain was performed which failed to reveal any evidence of cerebral hemorrhage. Magnetic resonance imaging of the brain demonstrated left sided acute infarcts in the middle cerebral artery and posterior inferior cerebellar artery territories. Ultrasonography of bilateral carotid arteries was reported to be normal. An echocardiogram performed at the outside hospital, demonstrated presence of a left atrial mass with a severely reduced left ventricular systolic function (ejection fraction 20%). One day later, the patient became lethargic and had multiple episodes of emesis. She became febrile (core body temperature 38.2 C), hypotensive with systolic blood pressure 60 mm Hg and developed significant degree of leucocytosis (WBC: 25200). She was electively intubated for airway protection. She was given empiric broad-spectrum antibiotics consisting of vancomycin, gentamicin and ceftriaxone. She developed a generalized erythematous rash to vancomycin and subsequently it was switched to daptomycin. In addition to antibiotics, she was also started on phenylephrine and norepinephrine infusions to maintain mean arterial blood pressure of 65 mm Hg. Laboratory work up was significant for positive cardiac biomarkers [CK-MB: 51 ng/mL (normal <8.8 ng/mL) and Troponin I: 4.8 ng/mL (normal <0.4 ng/mL)]. A repeat echocardiogram demonstrated reduction in the left ventricular ejection fraction to 10%. At this point, a decision was taken to transfer the patient to our hospital.
Figure 2: H&E stained section of
the excised mass under low power magnification.
The photomicrograph demonstrates
a bluish stroma containing areas of extensive
hemorrhage along with isolated and clustered tumor cells.
Hospital course at Cleveland Clinic
She was admitted to the coronary intensive care unit of our hospital. The patient was intubated but followed simple commands. Her vital signs were significant for fever (Temperature: 38.2 C), hypotension (BP: 88/61) and regular tachycardia (heart rate: 110). Neurological examination was significant for global weakness, worst in the left upper extremity. In addition, there was impairment of leftward gaze in her left eye.
Her initial laboratory examination was significant for anemia (hemoglobin: 10.6), leucocytosis (WBC: 21,870) and acute kidney injury (serum creatinine: 1.5 mg/dL). Evidence of myocardial injury was confirmed with elevated cardiac biomarkers (CK: 1352 ng/mL, CK-MB: 10.9 ng/mL and Troponin T: 0.79 ng/mL). Repeat computed tomography of the brain demonstrated evidence of subacute infarction involving multiple areas (Figure 1). Transthoracic echocardiography confirmed the presence of severely reduced ejection fraction and a large left atrial mass attached to the interatrial septum (Movie 1-2). There were regional wall motion abnormalities noted in multiple territories, most prominent in the apical region (Movie 1-2). Transesophageal echocardiography revealed a large mass in the left atrium 3.5 cm X 2.8 cm X 1.7 cm (Movie 3-4). The mass was noted to have a broad base of attachment to the interatrial septum and multiple frond like projections into the left atrial cavity (Movie 3-4).
Due to the devastating embolic complications of this mass, urgent surgical treatment was contemplated. It was evident that the patient had suffered cerebral embolic stroke and possibly acute myocardial infarction as a result of embolic occlusion of coronary arteries. The patient underwent an urgent coronary angiogram, which revealed completely normal coronary arteries. Presence of normal coronary arteries in the setting of multiterritorial wall motion abnormalities, predominantly involving the apex, suggested the diagnosis of Takotsubo cardiomyopathy.
Within 24 hours of her presentation to our hospital, the patient was moved to the operating room for resection of the atrial mass. Intraoperatively, the right atrium was opened and a large amount of septum was removed, in order to excise the atrial mass without disturbing it. The septotomy was closed using a piece of autologous pericardium. Subsequently, the patient was weaned off the cardiopulmonary bypass after closing the right atrium.
Histology/Pathology of the mass
Figure 3: H&E stained section of the
excised mass under high power magnification.
The photomicrograph demonstrates presence
of tumor cells in isolation and surrounding blood vessels.
In addition, several hemosiderin-laden macrophages
are visible scattered in the myxoid stroma.
Gross and histological examination of the mass was consistent with left atrial myxoma. Histological examination revealed a myxoid tumor with lepidic cells arranged in cords and ring structures. The stroma showed mononuclear infiltrates and hemosiderin-laden macrophages without neutrophils (Figures 2-3). The tumor was completely excised with a portion of normal myocardium at the base.
Post-operatively, the patient had a relatively uncomplicated clinical course. She was extubated on postoperative day 2, following which it was realized that she had lost complete vision in her left eye. Indirect ophthalmoscopy demonstrated presence of central retinal artery occlusion of subacute duration, which was attributed to be embolic sequela of the atrial myxoma. Five days after surgery, the left ventricular function had improved to 45%. She was discharged on the eighth post-operative day. Prior to her discharge, she had regained complete motor strength in all four extremities. However, the visual loss in the left eye was persistent.
Cardiac myxoma is the most commonly encountered primary tumor affecting the heart accounting for atleast half of all primary cardiac neoplasms . Up to half of the cardiac myxomas may produce systemic emboli . Emboli from the cardiac myxoma may lead to cerebral ischemia or infarction, myocardial infarction or peripheral embolism [2, 3, 4]. Of these complications, cerebral ischemia is the most commonly encountered embolic complication accounting for 0.5% of all strokes . Left atrial atrial myxomas have been occasionally associated with acute embolic occlusion of coronary arteries leading to acute myocardial infarction .
Our patient is unique due to her systemic presentation involving multiple organ systems. In order to provide the best possible care to this patient, a multi-disciplinary approach was warranted from the beginning. The initial differential diagnosis consisted of septic thrombus, atrial myxoma or atrial sarcoma. Regardless of the exact histological diagnosis, it was certain that the mass had potential to cause catastrophic embolic complications in this young patient. It was interesting to note the occurrence of Takotsubo cardiomyopathy in our patient. The syndrome is characterized by transient left ventricular dysfunction, perhaps attributable to the catecholamine surge in stressful situations . An acute drop in her ejection fraction was concerning for embolic occlusion of coronary arteries. However, multi-territorial wall motion abnormalities along with presence of typical apical ballooning were very suggestive of this syndrome, which were subsequently confirmed with coronary angiography.
The origin, progression and risk factors of atrial myxomas remain unclear. Although considered benign, there has been description of recurrence of myxoma after surgical excision . However, it is interesting to note that there are eight cases described in the literature reporting association between cardiac myxoma and migraine with aura . There have been hypothetical elucidations of mechanisms by which cardiac myxomas may trigger cortical spreading depression leading to migraine with aura. However, the exact mechanism remains unknown.
Dr. James Thomas, Tomsich Family Department of Cardiovascular Medicine, Section of Imaging
This case illustrates the importance of a multidisciplinary approach to cardiac masses and the utility of three-dimensional transesophageal echocardiography in guiding therapy. Several aspects of this case deserve comment. First is the prolonged prodrome of migraine and at least two transient ischemic events undoubtedly related to emboli from the growing mass. She subsequently presented with a devastating syndrome of aphasia and a mixture of cardiogenic and (apparently) septic shock. Given the clear-cut cerebral emboli, it was quite appropriate to be concerned that coronary emboli were responsible for her profound LV dysfunction. Fortunately, her coronaries were normal, indicating Takotsubo syndrome as the cause of her depressed EF, which subsequently impreoved to 45% just 4 days post-operatively. The timing of surgery in patients with large cerebral emboli is always challenging, due to the fear of hemorrhagic conversion with the large heparin doses needed intraoperatively. In this case, the clear danger of further emboli mandated urgent surgery, which was conducted successfully without any further neurologic complications. By the time of discharge, her speech was greatly improved and her right arm weakness was resolving.
The 3D TEE shown here is dramatic, showing a large, friable mass with multiple mobile protuberant fronds at risk for further emboli. Even more useful to those caring for her was the ability to explore this 3D dataset interactively, to determine the precise location of attachment to the interatrial septum and absence of any satellite lesions. Armed with this information, the surgeon was able to completely excise the myxoma blindly by approaching it from the right atrium with an excellent clinical outcome.
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