A patient with recurrent strokes: multimodal imaging reveals two possible causes

A cardio-embolic cause is seen in approximately 20% of patients with an ischemic stroke, mainly due to atrial fibrillation with thrombus formation in the left atrial appendage [1, 2]. However, in almost a quarter of stroke patients, no clear cause is identified, and half of these patients present with a right-to-left shunt or patent foramen ovale (PFO) [3]. Although atrial fibrillation is the main driver of cardioembolic strokes, less frequent causes such as cardiac tumors can be identified [4]. Cardiac tumors represent a rare occurrence in routine clinical practice. Nevertheless, the wide availability of echocardiography and other imaging diagnostic tools such as cardiovascular magnetic resonance imaging (CMR) and cardiac computed tomography angiography (CCTA) simplified the diagnosis of such structures, thereby enabling the clinician to establish an etiological diagnosis and appropriate therapy [5]. Cardiac tumors can involve any structure of the heart, and their clinical significance can vary from incidental findings during routine check-ups to catastrophic first clinical events such as ischemic stroke and sudden cardiac death [6]. Based on their origin, cardiac tumors can be classified as primary or secondary tumors of the heart, the latter being at least 20 times more frequent [7]. Cardiac myxomas are the most common primary cardiac tumor in adults, mostly located on the left side of the interatrial septum, followed by papillary fibroelastomas, which are usually located on the cardiac valves [8]. Cardiac fibroma is a type of primary cardiac tumor, mostly diagnosed in the pediatric population. Furthermore, the literature reports cardiac fibromas as being frequently located intramyocardially [9].

For most of the tumors attached to the endocardium, a surgical approach with excision is recommended due to their high embolic risk. Subsequent histopathological examination of the excised structure provides the definite diagnosis.

Herein, we present the case of a 67-year-old patient with a history of recurrent strokes in whom cardiac imaging revealed two possible causes for the embolic events.

A 67-year-old patient presented in our outpatient clinic for a transesophageal echocardiography (TEE) for the evaluation of a possible source of emboli in the context of two previous cryptogenic strokes (a transitory ischemic attack in 2019 and a stroke in the territory of the posterior inferior cerebellar artery in 2020). Apart from the two ischemic events, the patient had arterial hypertension, which was well controlled under calcium blocker (amlodipine 10 mg/day) and ß-blocker treatment (bisoprolol 2.5 mg/day). At time of presentation, the patient was on aspirin 100 mg/day, atorvastatin 40 mg/day, and ezetimibe 10 mg/day. Several previous Holter monitorings did not identify any episode of atrial fibrillation. A previous transthoracic echocardiography (TTE) showed a hypertrophied interventricular septum (12 mm), which was interpreted in the context of the hypertensive heart disease. Furthermore, a Duplex-examination of the carotid arteries identified a mild to moderate atherosclerosis without stenoses > 50%. Clinical examination performed before the TEE, including a complete neurological exam, showed no abnormal findings. Pulse, blood pressure, and oxygen saturation in peripheral blood were all within normal range. The ECG showed a normofrequent sinus rhythm (67/min), a regular electric axis of the heart, and no evidence of ischemic changes, conduction delays or repolarization abnormalities. The patient was afebrile in the previous six months. The TEE performed in light sedation (midazolam 2.5 mg i.v.) detected a mobile inhomogeneous mass attached to the right coronary cusp of the aortic valve, measuring 5 x 8 mm (Figures 1A and B). In Addition, a PFO was identified with a right-left shunt under Valsalva maneuver (Figures 1C and D). The left atrial appendage was free of thrombi, the heart valves did not exhibit any other abnormal findings, and no other sources of emboli were identified. According to the imaging examinations, the structure seen attached to the aortic valve was considered to be a papillary fibroelastoma. As a differential diagnosis, a Lambl's excrescence was considered. However, the morphological aspect was atypical for such a diagnosis. A valve vegetation in the context of an endocarditis was also considered as a possible differential diagnosis. This was however very unlikely, as the patient did not report any episodes of fever, and routine blood tests performed in the previous six months at the patient's general practitioner did not indicate an infection. Thus, two possible causes for the recurrent strokes, a papillary fibroelastoma and a PFO, were identified. The diagnosis was expanded with the performance of a CCTA. The structure found in the previous examinations was identified attached to the right coronary cusp of the aortic valve (Figures 2A, B, and C). In addition, a relevant coronary artery disease was excluded (Figure 2D, E, and F). This was especially important as an invasive angiography may have carried a minor risk of embolization.

Figure 1

Figure 2

The case was discussed in our heart team, and a surgical approach with closure of the PFO and simultaneous removal of the suspected papillary fibroelastoma was recommended. The surgical procedure was performed without complications. Histopathological examination revealed the presence of a fibroma, as the elastin stain did not identify any elastin fibers (Figure 3). The postoperative course was uneventful and the clinical and echocardiography follow-up at three months was normal.

Figure 3

A thorough cardiological evaluation is of paramount importance in patients who underwent an ischemic stroke, as it can identify the underlying cause in almost half of the patients [10]. Apart from Holter monitoring, aimed at detecting atrial fibrillation, cardiac imaging plays an important role in identifying possible sources of embolization. In this regard, the accurate diagnosis of cardiac masses has an important prognostic relevance, as it can alter the therapeutic approach in such patients [11]. Moreover, one of the main clinical expressions of a cardiac tumor is the occurrence of an ischemic event [6].

TTE is currently the cornerstone of clinical diagnosis in cardiology. It is especially useful for patients with an embolic event, because it can identify thrombi, cardiac tumors, a non-compaction pattern, or a reduced ventricular performance [12]. However, TTE is not sufficient to exclude an embolic source, as the left atrial appendage is usually not visualized in the transthoracic acquisitions. In addition, structures of the cardiac valves can also not be entirely visualized in TTE. In this regard, TEE is an excellent diagnostic method for patients with an embolic event, as it can readily identify cardiac thrombi with a particular focus on the left atrial appendage, as well as other cardiac masses, such as cardiac tumors attached to the cavity or valve endocardium. Furthermore, using agitated saline, possible shunts such as PFOs can be readily diagnosed [12]. This was the case in our patient, in whom TEE detected two possible causes for the recurrent strokes. In addition to echocardiography, CMR and CCTA were proven excellent tools for the evaluation of patients with cardiac masses. In particular, CMR can provide information related to tissue characterization and thus aid the clinician in establishing an etiological diagnosis [5]. Nevertheless, CMR is limited in the evaluation of small hypermobile structures, as seen in our patient, as the spatial and temporal resolution of the method do not allow for an appropriate perfusion and tissue characterization evaluation [13]. CCTA, on the other hand, is an excellent method for the analysis of small hypermobile structures [14]. Using a retrospective ECG-gated protocol, the entire volume of the heart can be acquired, and a 3-D reconstruction allows for an excellent morphological and functional characterization of the cardiac structures [15]. In addition, the coronary arteries can simultaneously be analyzed, thus obliterating the need for invasive coronary angiography in selected patients. This was especially important in our patient, as an invasive procedure might have resulted in an embolization of the tumor attached to the aortic valve.

The therapeutic approach in our patient was guided from the results of our non-invasive imaging tests. First, the endovascular closure of a PFO has recently been shown to provide protection against recurrent cryptogenic stroke [16]. However, the identification of a second possible source of emboli, which could not have been treated endovascularly, justified the decision for a surgical approach. The imaging tests pointed to a papillary fibroelastoma. This is the second most common primary cardiac tumor and the most common cardiac tumor of the aortic valve [17]. Papillary fibroelastomas usually measure around 10 mm in diameter and are usually solitary tumors. Their differential diagnosis consists mostly of Lambl's excrescence, vegetation or thrombus, and lastly other type of primary cardiac tumors. Lambl's excrescences exhibit mostly a “strand-like” appearance, and cardiac thrombi or vegetations would need an appropriate clinical context, which was not present in our patient [18, 19]. Nevertheless, the histopathological analysis revealed the cardiac tumor to be a fibroma. This is of particular interest, as these types of cardiac tumors are seen mostly in the pediatric population and are mostly located intramyocardially. However, several reports related to fibromas attached to the cardiac valves in adults exist in the literature [20].

This case highlights the importance of multi-modal cardiac imaging in the evaluation of patients with ischemic events. Starting with echocardiography and ending with cardiac computed tomography angiography, a complete pre-operative assessment was possible non-invasively. Lastly, clinicians should be aware that histopathological evaluations can still provide “surprise” diagnoses.