Blood cysts of the cardiac valves in adults: Review and analysis of published cases

Blood cysts of cardiac valves are generally seen in newborns and infants and very rarely in adults. Although in most cases they are incidental findings they may be associated to severe cardiac or systemic complications. This study analyzes incidence, presentation, and treatment of valvular blood cysts in adults.


| INTRODUCTION
Benign cardiac neoplasms are substantially rare and among these intracardiac cysts filled with blood are even more uncommon; indeed, they have not even been mentioned in a recent review of cardiac tumors reported by Tyebally et al. 1 However, mainly owing to advancement in diagnostic techniques, with a widespread use of and accessibility to multimodality imaging, an increase in the diagnosis of cardiac or pericardial masses has been observed recently and is expected to further grow in the future. 1 Intracardiac blood cysts (BCs) are commonly found in newborns and infants being rare after the first year of life, they mainly involve the cardiac valves and generally disappear during growth. 2 In adults they may occasionally be diagnosed, are usually located on all cardiac valves and chambers, the mitral valve (MV) being the most frequently involved; despite absence of histological malignancy BCs of the heart valves have been reported to cause life-threatening complications with even severe sequelae.
There is still uncertainty on the origin of BCs and controversy on whether medical treatment with continuous clinical and echocardiographic patient follow-up should be preferred to immediate surgical removal. The present review, analyzing the published cases, was undertaken with the aim of assessing the incidence, evaluating the clinical presentations, and discussing the treatment of BCs involving the cardiac valves in adults.

| METHODS
We have performed a search of the English literature, through PubMed and Medline, to identify all cases of BCs involving the MV, MV apparatus, and tricuspid, aortic and pulmonary valves (AV and PV) that have been so far reported. Articles in textbooks and meeting abstracts were excluded, as well as cases included in general reviews of cardiac tumors or clinical reports, when detailed clinical and pathological information on BCs, when present, was lacking. Cases of valvular cysts but with the uncertain histological diagnosis were excluded. The reference sections of pertinent articles were also evaluated as well as personal files and the archives of journals available on the CTSNet website. All reported cases observed in the pediatric population were excluded, considering only those occurring in patients ≥18 years of age.
Approval by the Ethical Committees was not required for this kind of study, as well as informed patient consent, provided that all relative data were treated anonymously.  9,21 and in one the BC caused severe MV regurgitation. 23 Except for the first two BCs cases described, diagnosed either by cineangiography 3 or M-mode echocardiogram, 5 in all other cases transthoracic 2D echo was used for evidencing the presence of an MV mass ( Figure 1). The diagnosis was confirmed by supplemental transesophageal echo in many cases and more recently by multimodality imaging, including angio-computed tomography, nuclear magnetic resonance, contrast real-time echocardiography, and 3D echo. 23,34,36,38,44,45,49,49,51 3.1.2 | Surgical data Cyst removal was performed in 37 patients (70%) while in 16 (30%) medical treatment and serial follow-up was recommended; in one patient AV and ascending aorta replacement were performed leaving in place a small BC on the MV. 20 Surgery was generally performed through a standard median sternotomy while in three cases a minimally invasive, endoscopic technique was used. 27,36,45 Two patients had previous open heart operations and required repeat sternotomies, 22,42 while one had a previous liver transplantation. 10 The BC was approached through a trans-aortic incision in 7 cases, through the left atrium in 6, trans-septal in 4, while in 20 cases it was not specified. Beside cyst removal, 27 patients (73%) had associated procedures: mitral valve replacement (MVR) in 12, mitral valve repair (MVr) in 9, coronary artery bypass grafting in 3, and combined MVR and AV replacement in 1. In addition, in two patients, with associated cor triatriatum, resection of the intraatrial band was performed. 14,24 No operative deaths are reported. published from 1991 to 2021 (Table 3).

| Patient characteristics
Of the nine patients, five were females and four males with an age ranging from 35 to 88 years (mean, 67 ± 15 years). Symptoms at presentation were generally not specific except for few cases with moderate-severe tricuspid regurgitation, with congestive heart failure or symptoms related to other concomitant cardiac pathology. One patient had an associated muscular ventricular septal defect without hemodynamic significance. 55

| Surgical data
Cyst removal was performed in six cases (55%) while in the remaining three, surgery was considered not indicated.
All patients were operated through a median sternotomy using a right atriotomy for cusp excision; in one case even a combined left atrial-transseptal approach is reported. In four patients, BCs removal was associated with various techniques of TV repair; in one patient myocardial revascularization was also performed.

| Patient characteristics
Our search yielded three papers on BCs of the PV, two case reports, 62,63 and one image in cardiovascular disease 64 (Table 4). All were females, 31, 43, and 44 years of age. Auscultation of a cardiac murmur, associated to fatigue and dyspnea, prompted further evaluation with angiographic or echocardiographic disclosure of the BC.
In two cases, the pulmonary trunk had an aneurysmal dilatation 62,64 and in one the PV was severely dysplastic. 64

| Surgical data
Cyst removal was performed in all cases, by a transpulmonary approach. In one patient, PV valvuloplasty was required associated to reduction of the pulmonary trunk size. 64

| BCs of the AV
We found only a case of a BC, on an images in cardiovascular medicine paper, found on a bicuspid AV in a 22-year-old male with aortic stenosis. The cyst had a maximum diameter of 21 mm with a broad base of implant; it was excised during AVR. 65

| BC pathology
BCs of the cardiac valves are usually described as round or ovalshaped masses, either bluish or yellowish in color, at times pedunculated and of variable sizes.
Mean maximum size of MV BCs was 20 ± 8 mm, ranging from 3 to 46 mm; in four cases the cyst was considered as "giant" despite a large variability of sizes. 7,9,26,32 The most frequent location of the cysts was the anterior mitral valve leaflet (AML) occurring in 33 cases,  one patient with two BCs both AML and PML were involved. 14 In three patients, two BC were found. 6,14,30 Some BCs have been described as multilobulated. 9,12,17,50 The maximum size of TV BCs ranged from 18 to 33 mm (mean, 24 ± 5 mm); in three cases the size of the BC was not indicated. 57,60,61 BCs were located on the septal TV leaflet in four, anterior TV leaflet in two, and the posterior TV leaflet in one case; in one patient location of the BC was not reported. 57 The maximum size of the three PV BCs was 8, 30, and 40 mm, respectively; according to the authors' description BCs were located on the posterior PV cusp in one case and on the right PV cusp in one; in one case the location is not clearly indicated. 64 Histology of the excised tissue has not been reported in all surgical cases. When available histologic data, regardless of BC location, have been substantially uniform in describing the BC wall as composed mainly by fibrous tissue of various thickness (Figure 2A), at times with a myxoid stroma. In many cases, the inner BC wall was lined with typical endothelium while smooth calcific spots were occasionally seen. 19,49 The fibrous nature of the BC wall is also confirmed by immunohistochemistry ( Figure 2B). Interestingly, no ultrastructural images have been reported in BCs excised from cardiac valves of human beings.

| DISCUSSION
The first description of an intracardial BC was reported by Elsässer as late as 1844, 66   This review has some limitations. Since we have excluded from our analysis cases possibly contained in specific textbooks or pathological reviews and those with an uncertain diagnosis, the number of MV BCs may be underestimated. Even if the American Academy of Pediatrics has identified the upper age limit as 21 years for pediatric patients, 70 we arbitrarily considered 18 years as the lowest age for this review; elevating this limit would have further reduced the number of recognizable cases. Although some of the data which could be obtained from single cases were not complete, this review provides enough evidence to assess the clinical presentation, diagnostic modalities, and management of patients with a cardiac valve BC found in adult patients.
In conclusion, BCs are rarely found in patients ≥18 years of age and predominantly affect the MV. Although in most cases they represent an incidental finding, sometimes they are heralded by serious acute complications such as syncope and stroke. For such reason, surgical removal, which is a low-risk procedure and can be performed with minimally invasive techniques, should be advisable for BCs of the MV, even if of small size; on the other hand, BCs in the right heart may be treated conservatively unless they cause TV regurgitation or obstruction to blood flow. The origin of valvular BCs is still quite uncertain but since their histological benign nature is well known further studies on pathogenesis would have only a speculative interest. It is likely that the current widespread use of multimodality imaging will increase the number of intracardiac BC detected and hopefully the present review will help to improve the management of such patients.