Cardiac myxoma and its implications for cardioembolic stroke

Abstract

Cardiac myxoma (CM) is the most common type of primary cardiac tumor and a major embolic source of cardioembolic stroke. Two potential causative mechanisms are associated with CM-related ischemic stroke (CM-IS): Embolism from detached tumor debris and metastatic infiltration. The risk factors for embolism from CM remain unclear and are widely debated in the literature. CM-IS often initially presents with central nervous system complications. Diagnosis requires a comprehensive assessment of clinical manifestations, imaging findings, and laboratory test results, with histopathological examination required for a definitive diagnosis. Surgical resection of myxoma is the most effective CM-IS treatment, although the optimal timing and approach remain controversial. This review consolidates the current knowledge on CM-IS, identifies critical risk factors for embolic complications, and discusses contemporary treatment strategies, emphasizing the need for individualized management protocols and further research to improve outcomes in affected patients.

Key Words: Myxoma; Cerebral embolism; Cardioembolic stroke; Ischemic stroke; Mechanism; Risk factors; Diagnosis; Treatment

Core Tip: Cardiac myxoma, although rare, is a significant cause of cardioembolic stroke in young adults, often due to embolism from tumor fragments or metastatic spread. The link between tumor mobility, morphology, and stroke risk remains unclear. This article explores the relationship between cardiac myxoma and ischemic stroke (CM-IS), highlighting two potential pathogenetic mechanisms and identifying tumor morphology and mobility as critical risk factors. CM-IS predominantly affects younger patients presenting with acute neurological symptoms, necessitating tailored diagnostic and therapeutic approaches. The analysis highlights the complexity of CM-IS and calls for further research to refine its management and support clinical decision making.

INTRODUCTION

Cardiac myxoma (CM) is the most common type of cardiac tumor, accounting for 50%-85% of all benign cardiac tumors[1,2]. The overall low incidence of cardiac tumors (only 0.02% of all tumors during autopsies[3]) renders CM a rare disease, with an incidence of approximately 0.5 to 1 per million individuals. A prospective study of 402 patients with cardioembolic cerebral infarction revealed that only 4 cases were associated with cardiac tumors[4]. Although the overall incidence of cardiac tumors and their related strokes is low in the general population, embolic events remain common and serious complications of CM, occurring in 20%-45% of cases[5], with cerebral embolism constituting 50% of all embolic events and representing a significant cause of cardioembolic stroke[6]. Considerable controversy persists regarding the causative mechanisms, risk factors, optimal timing of surgery, pharmacological treatment, and short- and long-term complications of CM-related ischemic stroke (CM-IS).

For this updated review, we systematically searched PubMed, Embase, and Web of Science databases for studies published between January 2000 and July 2025 using the keywords “cardiac myxoma”, “ischemic stroke”, “cardioembolic stroke”, and “neurological complications”. We included original research articles, systematic reviews, and large case series on CM-IS pathogenesis, risk factors, clinical characteristics, diagnostic approaches, or treatment. Single-case reports without an accompanying literature review and non-English publications were excluded. This article summarizes the pathogenesis, risk factors, clinical manifestations, and recent advances in the diagnosis and treatment of CM-IS.

PATHOPHYSIOLOGICAL MECHANISMS

To date, two potential causative mechanisms have been proposed for the pathogenesis of CM-IS: Embolism from detached tumor debris and metastatic infiltration. The first mechanism suggests that tissue fragments, thrombi, or a combination of both detach from the tumor mass owing to its gelatinous structure, migrate into the circulation, and occlude the cerebral vessels[7-9]. The second mechanism proposes that myxomatous cells shed from the tumor tissue, spread to the brain, infiltrate cerebral vessels, and cause focal alterations of the internal elastic lamina, leading to tumor seeding and growth, which can result in central nervous system metastases and recurrent brain infarctions[10,11]. Intriguingly, in our recent study, we identified multiple differentially expressed genes (miRNAs, lncRNAs, and mRNAs) in the plasma and tumor-derived exosomes of patients with CM-IS using RNA-seq datasets[12]. This finding seems significant because tumor-derived exosomes have been reported to play critical roles in tumor growth, metastasis, and immunoregulation[13,14]. Further research is needed to elucidate the pathogenesis and mechanistic actions of these exosomes in the context of CM-IS.

RISK FACTORS

Previous studies have identified several risk factors for embolic complications in CM, including tumor type, size, location, and mobility; patient sex; platelet count; and lower B-type natriuretic peptide levels[15-18]. Among these factors, tumor fragments or tumors with high mobility have been associated with an increased incidence of cerebral embolism[18,19]. A general consensus exists across studies regarding the relationship between tumor mobility and morphology and CM-related stroke[19-22]. However, the influence of tumor size on the occurrence of stroke related to CM remains contentious[18,21,23,24], necessitating further research.

CLINICAL CHARACTERISTICS

Although CM is relatively rare (< 0.5%), it remains a significant source of emboli, particularly in young adults presenting with stroke[25]. Several studies have reported that stroke caused by CM mainly affects young women in their third and sixth decades of life[17,26,27]; however, our recent multicenter study showed no female predominance, demonstrating a female-to-male ratio of 1:1[18]. Unlike cerebral aneurysms or metastatic brain tumors, CM-IS is typically associated with an acute onset, where initial symptoms mainly comprise hemiplegia, aphasia, altered consciousness, dysarthria, and ataxia, while some cases present with concomitant constitutional, cardiac, and/or neurological symptoms[18,26,28]. In the acute phase, more than half of patients presented with relatively mild or moderate clinical deficits[18,21,27], with a low incidence of early neurological deterioration[18]. Additionally, the involvement of a single cerebral vessel (predominantly the middle cerebral artery) and multiple territories were common among patients with CM-IS[18,21,26]. The most frequently affected areas are the basal ganglion and frontal, parietal, temporal, and cerebellar areas, all of which correspond well with neurologic deficits such as hemiplegia, hypoesthesia, and aphasia[18]. Consequently, brain imaging should be performed in all patients with CM who present with immediate neurological deficits. However, the clinical features of CM-IS related to metastatic infiltration remain largely unexplored owing to the rarity of such cases[10,11].

DIAGNOSIS

The diagnosis of CM-IS relies on clinical features (non-specific cardiac, embolic, and constitutional symptoms), imaging (cranial and cardiac), and laboratory investigations, with definitive diagnosis established through histopathological examination of the mass[29]. When CM-related stroke is suspected, cranial magnetic resonance imaging (MRI) should be performed early, especially during the hyperacute phase, to facilitate further management and gain valuable time. Comprehensive cranial MRI and vascular assessments should be completed prior to tumor resection because CM can metastasize intracranially, leading to intracranial aneurysms or myxomas. Echocardiography is the preferred diagnostic modality for CM and is capable of delineating the size, location, attachment, and mobility of the atrial mass as well as the degree of circulatory obstruction caused by the tumor, thereby aiding in the assessment of embolic event risk. Representative transthoracic echocardiographic images are shown (Figure 1). Among echocardiographic assessments, transesophageal echocardiography is superior to transthoracic echocardiography in characterizing atrial masses, despite being relatively simpler to perform[30]. Cardiac MRI can also assist in diagnosing CM, visualizing the tumor's anatomy, pericardial and pleural effusion, and providing insight into intratumoral vascularization via T1- and T2-weighted imaging[27,31]. For patients undergoing surgical resection of a CM, coronary angiography should be integrated into the routine preoperative evaluation[32]. Additionally, laboratory tests, such as those that measure serum interleukin-6 levels, can reflect the anatomical characteristics of the CM (e.g., tumor diameter, volume, and irregular tumor surface)[33,34]. However, to date, no universal diagnostic criteria for CM-IS have been established, although we first proposed cardioembolic stroke-based diagnostic criteria along with key points for the clinical diagnosis of CM-IS (Table 1)[35].

Figure 1 Transesophageal echocardiographic findings of left atrial mass. A: Round mass was visualized in the left atrium, confined within the left atrium during systole; B: The mass extended into the left ventricle during diastole.

Table 1 Key points for clinical diagnosis of cardioembolic stroke.

Key points	Substance
Clinical features	More common in mid-aged and young women; typical symptoms of cardioembolic stroke
Brain imaging (CT/MRI)	Unilateral multi-territory infarcts (basal ganglia, cerebellum, parietal lobe, and temporal lobe), predominantly involving middle cerebral artery; cerebral hemorrhage or mucinous metastases are rare
Vascular imaging (CTA/MRA, DSA)	A single cerebral artery (especially the MCA) or multiple cerebral arteris stenosis, presenting as multi-segmental occlusion; accompanied by cerebral aneurysms or pseudoaneurysms
Cardiac findings	Confirmed cardiac myxoma
Laboratory findings	Increased serum level of erythrocyte sedimentation rate and C-reactive protein
Differential diagnosis	Exclusion of other diseases

CT: Computed tomography; MRI: Magnetic resonance imaging; DSA: Digital subtraction angiography; MCA: Middle cerebral artery; CTA: Computed tomography angiography; MRA: Magnetic resonance angiography; CM-IS: Cardiac myxoma-induced stroke.

TREATMENT

To date, no clear guidelines exist regarding the treatment options for CM-IS. The use of intravenous thrombolysis and mechanical thrombectomy (MT) in these patients was based solely on previously published case reports, with no reliable evidence supporting its clinical utilization. Thrombolysis has been administered on several occasions in patients with CM-IS, yielding variable degrees of success or failure[21,36-42]. We hypothesize that the composition and heterogeneity of the clot in CM-IS patients may influence the efficacy of both treatment modalities, as emboli can consist of tissue, thrombi, or a combination of both[43,44]. Theoretically, thrombotic embolisms could benefit more from thrombolysis. MT appears to be more effective for treating these patients and producing symptomatic alleviation[45-49]. More importantly, it can provide relevant information regarding the etiology of CM-IS through pathological examination of the retrieved clot. Currently, the evidence-based time window for thrombectomy and endovascular methods is not well defined. Upon review, MT was performed in patients with anterior circulation strokes within 4.5-6 hours[45,50] and posterior circulation strokes within 23 hours of symptom onset[47]. Moreover, MT with stent retrievers appears safe and effective for the rapid recanalization of large vessels secondary to CM, yielding favorable functional outcomes[47,50,51].

The definitive therapy for CM is complete surgical resection of the tumor to prevent further complications[9,52]. However, no consensus exists regarding the appropriate timing for cardiac surgery or surgical approaches following ischemic stroke in these cases. Some studies favor surgical intervention immediately or within 48 hours after ischemic stroke onset[53,54], albeit with uncertainty regarding the exact timing[55]. Conversely, other studies support delayed surgical intervention at 5 days or 7 days[36,45] or 3-4 weeks[21] following stroke onset. da Silva and de Freitas[56] suggested that for patients with CM-IS with severe symptoms and large infarcts, surgical resection should be postponed, while in patients with mild symptoms and small infarcts, early surgery may be warranted.

Advancements in surgical techniques have enabled myxoma excision using various methods, including classical surgery (median sternotomy), minimally invasive approaches (right anterolateral minithoracotomy), and robot-assisted interventions. Among these techniques, minimally invasive approaches and robotic surgery have demonstrated advantages over median sternotomy in relation to hospital stay, blood loss, and the risk of complications such as stroke, although data on these two methods remain limited due to the rarity of CM[52]. We propose that the timing and selection of surgical resection should be individualized, taking into account the tumor size, location, patient condition (e.g., disease severity and infarct size), and surgeon’s expertise. Nevertheless, further studies are needed to develop individualized, multidisciplinary, and comprehensive treatment protocols and to validate the long-term efficacy of surgical methods, particularly minimally invasive and robotic approaches.

The present case also has important clinical relevance. It highlights the diagnostic challenges of CM-IS, especially in patients presenting with acute ischemic stroke but lacking conventional vascular risk factors. This scenario underscores the necessity of early cardiac evaluation, including echocardiography, in cryptogenic stroke cases to promptly identify potential cardiac sources of embolism. Furthermore, it illustrates the importance of integrating neurological and cardiological assessments to determine the optimal timing for intervention. By placing this case in the context of the existing literature, it reinforces the need for heightened clinical awareness and multidisciplinary collaboration to improve patient outcomes in CM-IS. A summary of the major case series and cohort studies on CM-IS, highlighting their diagnostic and therapeutic characteristics, is provided in Table 2.

Table 2 Summary of major case series and cohort studies on cardiac myxoma-related ischemic stroke from the neurological literature.

Ref.	Country	Sample size	Mean age (years)	Sex (male/female)	Tumor location	Neurological manifestations	Diagnostic modalities
Ekinci EI and Donnan[57], 2004	Australia	72	48	28/44	LA (90%), RA (10%)	Ischemic stroke, TIA, seizures	TTE, TEE, MRI
Zhang et al[21], 2021	China	37	46	16/21	LA (95%), RA (5%)	Multiple territory infarcts, recurrent emboli	MRI, CTA, TEE
Wu et al[45], 2024	China	15	50	6/9	LA (87%), RA (13%)	Large vessel occlusion	MRI, DSA, MT
El Sabbagh et al[29], 2017	United States	12	49	5/7	LA (100%)	Stroke, systemic embolism	TTE, TEE, MRI
Takach et al[58], 1998	United States	19	45	8/11	LA (84%), RA (16%)	Stroke, embolic events	Echo, MRI

LA: Left atrium; RA: Right atrium; TTE: Transthoracic echocardiography; TEE: Transesophageal echocardiography; MRI: Magnetic resonance imaging; CTA: Computed tomography angiography; DSA: Digital subtraction angiography; MT: Mechanical thrombectomy; TIA: Transient ischemic attack.

CONCLUSION

Despite significant research progress in the field of CM-IS over the past decades, substantial uncertainty or controversy remains regarding its pathogenesis, risk factors, diagnosis, and therapy, primarily owing to the rarity of the disease. Two potential causative mechanisms, embolism from detached tumor debris and metastatic infiltration, may underlie CM-IS pathogenesis. The risk factors for embolism caused by CM include tumor mobility and morphology, although the role of tumor size is subject to significant debate across studies. CM-IS often initially presents with central nervous system complications, and its diagnosis requires a comprehensive assessment of clinical manifestations, imaging findings, and laboratory tests, with histopathological examination of the CM required for confirmation. Although surgical resection of myxoma remains the most effective treatment for CM-IS, the optimal timing and surgical approach have been contested. Large-sample studies are required to clarify these issues. However, the present review has certain limitations. The literature is constrained by the rarity of CM-IS, predominance of retrospective case series, lack of large-scale prospective studies, and heterogeneity of diagnostic and therapeutic approaches. These factors restrict the generalizability of the current evidence and preclude definitive recommendations in some areas. Additionally, our work may have been influenced by selection bias despite the use of a systematic literature search strategy owing to the narrative review design.

Several avenues warrant further investigation. Large-scale, multicenter, prospective studies are essential to better define the incidence, risk factors, and natural history of CM-IS. Molecular and genetic profiling of CMs may help to elucidate the mechanisms underlying embolic events and potential metastatic behavior. The development of standardized diagnostic algorithms that integrate neurological and cardiological evaluations could facilitate timely and accurate diagnosis. Finally, comparative studies evaluating the timing and surgical techniques, including minimally invasive and robot-assisted approaches, are needed to optimize patient outcomes.