Right Atrial Non-Valvular Papillary Fibroelastoma Causing Paradoxical Embolic Stroke Through an Ostium Secundum Atrial Septal Defect: A Case Report

Abstract

Papillary fibroelastoma (PFE) is a rare benign cardiac tumor, usually left-sided and valvular. Right-sided, non-valvular PFEs are uncommon, and systemic embolization from these lesions is particularly rare, typically requiring an interatrial shunt. We report a surgically confirmed right-atrial, non-valvular PFE presenting with paradoxical embolic stroke through an ostium secundum atrial septal defect (ASD). A 72-year-old woman with recurrent ischemic cerebrovascular events was admitted with an acute posterior circulation stroke. Transthoracic echocardiography was nondiagnostic. Transesophageal echocardiography revealed a 13 x 14 mm highly mobile mass attached to the free wall of the right atrium and an ostium secundum ASD (about 9–10 mm) with bidirectional shunting. Surgical resection of the mass with concomitant ASD closure was performed 14 days after the index stroke. Gross inspection suggested a frond-like tumor; histopathology confirmed PFE. Postoperative recovery was uneventful. Anticoagulation was resumed for a new distal deep-vein thrombosis, and no further embolic events have occurred during follow-up. This case illustrates an unusual mechanism of systemic embolism from a right-sided, non-valvular PFE via paradoxical embolization through an ASD. It emphasizes the limitations of transthoracic echocardiography in detecting small or atypically located PFEs and supports transesophageal echocardiography as the modality of choice when clinical suspicion persists. In symptomatic patients or after embolism, surgical excision, particularly with simultaneous closure of right-to-left shunts, should be considered to minimize recurrence risk. Clinicians should include PFE in the differential diagnosis of recurrent cryptogenic stroke and actively search for interatrial shunts when right-sided tumors are suspected.

Case Presentation

A 72-year-old woman from Bogotá, Colombia, with a history of insulin-treated type 2 diabetes mellitus, dyslipidemia, high cardiovascular risk, and recurrent ischemic cerebrovascular events — the first at age 61 (May 2008) and the second at age 70 (December 2017) — presented to the emergency department with a 3-hour history of severe epigastric pain, vomiting, drowsiness, vertigo, and right upper-limb distal tremor causing gait limitation. Both prior cerebrovascular events were thought to be related to paradoxical embolization in the setting of distal deep-vein thrombosis (DVT) of the left lower limb. The 2008 cerebrovascular event was managed elsewhere, and most of the patient’s follow-up between 2008 and 2017 took place outside our institution; therefore, the extent of her prior diagnostic workup is only partially known from external records. Among these records, a transthoracic echocardiogram (TTE) performed in 2004 identified a patent foramen ovale (PFO) with associated pulmonary hypertension. Subsequent transesophageal echocardiography later demonstrated that the interatrial communication was more consistent with an ostium secundum atrial septal defect (ASD). At that time, the pulmonary hypertension was attributed to alveolar hypoventilation in the setting of suspected obstructive sleep apnea, with long-term home oxygen therapy subsequently initiated. The 2017 event represented her first presentation to our institution, during which transesophageal echocardiography (TEE) was attempted on two occasions but could not be completed due to lack of patient cooperation, and outpatient completion was ordered. As a result, definitive characterization of the interatrial defect and consideration of closure were delayed. The patient had been maintained on outpatient anticoagulation with a vitamin K antagonist; however, the international normalized ratio (INR) on admission was subtherapeutic (INR 1.6), consistent with a pattern of variable anticoagulation control documented on multiple prior outpatient measurements.

On evaluation, the patient appeared unwell and somnolent. Vital signs were as follows: heart rate 65 beats/min, blood pressure 126/56 mmHg, respiratory rate 19 breaths/min, and peripheral oxygen saturation 89% on room air. Abdominal examination revealed epigastric tenderness without peritoneal signs. Cardiovascular examination demonstrated regular heart sounds without murmurs. Pulmonary examination disclosed bibasal hypoventilation without added sounds. Neurologic examination was notable for language blocking, paraphasia, scanning dysarthria, naming deficits, and impaired comprehension. The 12-lead electrocardiogram (ECG) demonstrated sinus rhythm with a normal axis (Figure 1). Laboratory results, including blood counts, serum amylase, electrolytes, and cardiac troponin, were unremarkable; selected values are summarized in Table 1. Given the presenting complaint of epigastric pain, an abdominal etiology was investigated; liver function tests, serum amylase, and abdominal ultrasonography were all unremarkable. The abdominal pain subsequently resolved and was considered likely related to the posterior circulation ischemic event.

Figure 1.

Electrocardiogram showing sinus rhythm at 71 beats/min, normal axis, and no acute ischemic changes

Table 1.

Laboratory Findings

Lab finding	Value
Leukocyte count (cells/mm³)	10,100
Hemoglobin (g/dL)	15.2
Hematocrit (%)	44.5
Platelets (×10³/µL)	189
Creatinine (mg/dL)	0.64
Blood urea nitrogen (mg/dL)	13.2
Alanine aminotransferase (U/L)	24
Aspartate aminotransferase (U/L)	23
Bilirubin (mg/dL)	Total: 0.94 (Direct: 0.12)
Alkaline phosphatase (U/L)	53
Electrolytes	Sodium: 140; Chloride: 106
	Calcium: 9.4; Potassium: 3.6
	Magnesium: 1.7
Lactate (mmol/L)	1
INR	1.6
Lipid profile (mg/dL)	Total cholesterol: 81; HDL: 30
	LDL-C: 23.6; Triglycerides: 137
Amylase (U/L)	65
TSH (µU/mL)	1.85
HbA1c (%)	6.8

Note. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; HDL, high-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; INR, international normalized ratio; TSH, thyroid-stimulating hormone; HbA1c, glycated hemoglobin.

Noncontrast head computed tomography (CT) demonstrated a subtle corticosubcortical hypodensity involving the inferior, posterior, and medial aspects of the left cerebellar hemisphere, compatible with acute ischemia in the posterior inferior cerebellar artery (PICA) territory. Brain magnetic resonance imaging confirmed an acute infarct in the left PICA territory without hemorrhagic transformation. In light of the new stroke, warfarin was withheld and a thrombophilia workup — including antiphospholipid antibodies and protein C/S levels — was requested.

TTE was nondiagnostic for an intracardiac source of embolism. TEE revealed a highly mobile, spherical, echodense mass measuring 13 × 14 mm, attached to the free wall of the right atrium (RA) near the superior vena cava (SVC) junction, without a clearly defined pedicle and without extension into the SVC (Figure 2). The interatrial septum demonstrated aneurysmal excursion of 17 mm, with a defect consistent with an ostium secundum ASD measuring approximately 9–10 mm. Color Doppler demonstrated bidirectional flow with a predominant left-to-right shunt. Agitated-saline contrast study confirmed early microbubble passage across the defect, consistent with interatrial shunting. The left ventricle was of normal size with mild concentric hypertrophy, a left ventricular ejection fraction of 55%, and no regional wall-motion abnormalities.

Figure 2.

Transesophageal echocardiography.

Following multidisciplinary heart-brain team discussion, surgical management was recommended. After carefully weighing the risk of hemorrhagic transformation associated with cardiopulmonary bypass against the risk of further embolization, the patient underwent right atrial mass excision with concomitant primary ASD closure on day 14 after the index stroke. Preoperative coronary angiography demonstrated no obstructive coronary disease. Intraoperatively, a friable, gelatinous mass of approximately 2 cm was identified and resected en bloc with a small segment of the RA wall. An ostium secundum ASD of approximately 10 mm, with a lax septum and absent aortic rim, was closed using an autologous pericardial patch. The left atrium (accessed via the ASD) and right ventricle were explored with no additional masses identified. Grossly, the tumor resembled a myxoma; however, histopathological examination revealed avascular collagen-elastin papillary fronds covered by endothelium, consistent with a papillary fibroelastoma (PFE).

The postoperative course in the cardiovascular intensive care unit was uneventful, with no vasopressor support required. During hospitalization, a new distal DVT was detected, and anticoagulation with warfarin was restarted, achieving therapeutic INR levels. The patient was discharged without further complications, and at 24 months of follow-up, no recurrent embolic events have been documented.

Discussion

This report illustrates an atypical presentation of papillary fibroelastoma (PFE) for several reasons. First, PFEs most commonly arise on left-sided valvular structures; a right-sided, non-valvular lesion is exceedingly uncommon in a tumor already infrequent in the general population. ¹ Second, despite multiple evaluations, transthoracic echocardiography (TTE) did not identify the mass, even though TTE is generally considered adequately sensitive for PFEs. ¹ Small, non-valvular right-atrial lesions—especially near the SVC—may elude TTE, making transesophageal echocardiography (TEE) decisive when clinical suspicion persists. Third, our patient’s TEE did not display the classic “mottled/stippled” edge pattern often described for PFEs, reminding clinicians that imaging appearances vary and diagnosis must integrate clinical context and multimodality findings.

Right-sided PFEs typically embolize to the pulmonary circulation, sometimes presenting as pulmonary embolism in otherwise low-risk young patients. ² By contrast, systemic embolism from right-sided PFEs is unusual and usually requires an interatrial shunt—as in this case with an ostium secundum ASD—making the presentation particularly uncommon and rarely reported. (An interatrial shunt had been labeled PFO in 2004; current imaging documented an ostium secundum ASD.)

Primary cardiac tumors are rare. ³ In a large autopsy series (∼12,000 cases), their incidence was ∼0.056%, ⁴ whereas secondary (metastatic) tumors are nearly 20-fold more common. ⁵ Many primary tumors are asymptomatic and discovered incidentally.

PFEs are second only to myxomas in frequency, accounting for 4.4%–8% of primary cardiac tumors. ⁶ Echocardiography-based series suggest PFEs may now be the most frequent tumor identified in practice. ⁷ They typically occur between the fourth and eighth decades, most often on valvular endocardium but can arise on any endothelial surface, including the left ventricle. ² Reported valvular distribution: aortic 36.4%, mitral 29.4%, tricuspid 10.6%, pulmonary 7%. ⁸

The pathogenesis remains uncertain (neoplasm, hamartoma, organized thrombus, post-traumatic lesion, chronic infection).^9-11 Clinically, PFEs are often incidental; however, their friable fronds predispose to fragmentation and embolization, for which thrombolysis may be ineffective. A mucopolysaccharide-rich surface may harbor adherent thrombus that can embolize. ⁷ Retrospective series describe stroke/TIA risk ranging 13.5%–53.6%; in patients managed non-surgically, 31-month follow-up showed 16%–24% recurrence of neurologic events. ¹² Other manifestations include sudden death, valvular obstruction,^13,14 pulmonary embolism, ¹⁵ coronary embolization with myocardial infarction,^5,16 and retinal artery occlusion. ¹⁷

Echocardiography is the cornerstone for detection. The diagnostic performance of transesophageal echocardiography (TEE) is high, with reported sensitivity and specificity of 88.9% and 87.8%, respectively. ¹⁸ Typical features include a homogeneous mass with regular borders and a stippled peripheral pattern correlating with papillary projections; about 43.6% are mobile and 6.1%–8.6% are multiple.^8,18 Cardiac CT/MRI can complement assessment. Histopathology demonstrates avascular papillary fronds of elastin and immature collagen covered by a single endothelial layer, confirming PFE. ¹⁹

Management is guided by presentation. In symptomatic patients or those with prior embolic events, surgical excision is strongly recommended unless contraindicated, yielding very low recurrence and substantial reduction in embolic risk.^2,15 For incidental PFEs, decisions are individualized; mobile or >1 cm lesions—particularly left-sided—are often considered for resection in low-risk patients. Excision is also advisable for right-sided tumors when an interatrial shunt(PFO/ASD) coexists due to the risk of paradoxical embolism.^6,18 For lesions <1 cm without high-risk features, some experts favor close imaging surveillance before surgery. ⁶

Our patient’s recurrent ischemic events align with the elevated neurologic risk reported when PFEs are not excised after embolic presentation. ¹² Following tumor resection and ASD closure, she has had no recurrent events to date, consistent with series showing marked risk reduction and low regrowth—though recurrences are documented.^18,20 The concomitant closure of the ostium secundum ASD likely eliminated the pathway for paradoxical embolization and was pivotal to the favorable outcome. Although coexistence of PFO/ASD with PFE has been reported,^21-23 we identified only one case closely resembling ours. ²⁴

Several practical lessons emerge from this case. First, incomplete evaluation of prior cerebrovascular events may delay recognition of uncommon cardioembolic sources. Before the 2017 hospitalization, the patient had experienced only 1 prior cerebrovascular event, which may have contributed to a less extensive earlier extrainstitutional evaluation. In our patient, the 2008 event was managed elsewhere, and although transesophageal echocardiography was planned during the 2017 institutional hospitalization, it could not be completed despite 2 attempts because of poor patient cooperation. This delayed definitive characterization of the interatrial defect and consideration of closure, contributing to a prolonged diagnostic interval despite multiple nondiagnostic TTEs. In patients with recurrent cryptogenic stroke, a nondiagnostic TTE should prompt TEE, or cardiac CT/MRI when TEE is unavailable. Second, the timing of surgery required careful balancing of the early risk of hemorrhagic transformation after stroke against the high risk of further embolization. Anticoagulation was restarted for a new distal DVT, rather than as PFE-specific secondary prevention, highlighting the evidence gap regarding antithrombotic strategies in nonsurgical candidates.

In summary, although papillary fibroelastoma is uncommon, it should remain in the differential diagnosis of recurrent cryptogenic stroke, particularly when an interatrial shunt is present. In right-sided PFEs, careful assessment for PFO/ASD is essential, as shunt closure at the time of tumor resection may help prevent paradoxical embolism.

Conclusions

Right-sided, non-valvular papillary fibroelastoma (PFE) can cause systemic embolism when an interatrial shunt is present. In patients with recurrent cryptogenic stroke and a nondiagnostic transthoracic echocardiogram, transesophageal echocardiography is crucial to identify small or atypically located tumors and to detect shunts. Combined tumor excision and closure of the interatrial defect provided durable prevention of recurrent embolic events in this case.

Supplemental Material

Supplemental material - Right Atrial Non-Valvular Papillary Fibroelastoma Causing Paradoxical Embolic Stroke Through an Ostium Secundum Atrial Septal Defect: A Case Report

Supplemental material for Right Atrial Non-Valvular Papillary Fibroelastoma Causing Paradoxical Embolic Stroke Through an Ostium Secundum Atrial Septal Defect: A Case Report by Ivan Felipe Manrique Osorio, Martin Rebolledo, Karen Alvarez, Wilson Bohorquez in Journal of Investigative Medicine High Impact Case Reports