Diagnosis and treatment options for sinus of Valsalva aneurysms: A narrative review

Abstract

Sinus of Valsalva aneurysm (SoVA) is a rare cardiac defect that may be congenital or acquired. It is characterized by abnormal dilatation of the aortic root due to a weakened elastic lamina at the junction of the annulus fibrosus and the aortic media. SoVAs are present in approximately 0.09% of the general population and comprise up to 3.5% of all congenital cardiac defects. It is usually found incidentally on cardiac imaging, with a higher incidence observed in the Western populations and a male-to-female ratio of 4:1. A transthoracic two-dimensional echocardiogram is the initial diagnostic test of choice, which may reveal the characteristic “windsock deformity” that clinches the diagnosis. Other imaging modalities, such as transesophageal echocardiography and cardiac computed tomography angiography, help provide more extensive details of the aneurysm and its adjacent structures. Management options for ruptured and unruptured SoVA include surgical repair or transcatheter closure, which serves as a game-changing development in treatment. This article aims to provide background information on the epidemiology, pathophysiology, diagnosis, and recent advancements over the past decade in the management of SoVAs.

Key Words: Sinus of Valsalva aneurysm; Bicuspid aortic valve; Echocardiography; Cardiac computed tomography; Cardiac magnetic resonance imaging; Ventricular septal defect; Pulmonary stenosis; Atrial septal defect

Core Tip: Sinus of Valsalva aneurysm is a rare cardiac defect defined as an abnormal dilatation of the aortic root. This arises due to a weakened elastic lamina at the junction of the annulus fibrosus and the aortic media. Echocardiography is the first-line imaging of choice for diagnosis. Definitive management includes surgery. However, transcatheter closure is a newer minimally invasive technique that is now increasingly preferred over traditional surgical approaches in the treatment of both ruptured and unruptured aneurysms.

INTRODUCTION

Sinus of Valsalva aneurysm (SoVA) is an uncommon cardiac defect characterized by an abnormal dilatation of the aortic root between the sinotubular ridge and the aortic valve annulus[1]. They can be congenital or acquired and are more common among men than women, with a reported incidence of 0.09% in the general population[1,2]. Congenital cases are commonly associated with other cardiac anomalies, such as bicuspid aortic valves (BAVs), pulmonary stenosis (PS), and ventricular septal defects (VSDs)[3,4]. Inherent deficiency of the elastic lamina in the affected aortic sinus is the common underlying mechanism of most SoVA[5]. Over time, this structural abnormality under long-standing pressure leads to progressive aneurysmal dilatation and eventual rupture[5,6].

SoVAs commonly originate from the right coronary sinus in 70% to 90% of cases, followed by the noncoronary sinus (10%-25%) and the left sinus (< 5%)[7]. Patients may present asymptomatic or symptomatic with symptoms suggestive of acute rupture, such as dyspnea, chest pain, cardiac murmurs, and palpitations[7,8]. Unruptured aneurysms are usually clinically silent and are commonly discovered incidentally on echocardiography or cross-sectional imaging performed for other reasons[7-9].

Treatment of SoVA has evolved over the last decade. Although surgical repair remains the definitive management option, transcatheter closure (TCC) is a minimally invasive technique that has emerged in the previous two decades[10]. This procedure treats both ruptured and unruptured aneurysms and has expanded the range of nonsurgical options for patients with SoVA[10,11]. In this article, we provide a narrative review of SoVA and its epidemiology, pathophysiology, diagnosis, and management.

EPIDEMIOLOGY

SoVAs are extremely rare, occurring in approximately 0.2% to 0.9% of patients undergoing cardiac surgery[5,12,13]. These aneurysms constitute up to 3.5% of all congenital cardiac anomalies, with an even lower reported incidence of 0.09% in the general population[14-16]. Due to its rarity, many cases of SoVAs remain clinically silent until an adverse event such as rupture occurs[17]. Congenital SoVAs typically occur in younger people and are 4 times more likely in men compared to women, with a higher reported incidence in the Western population[18,19]. This higher incidence in Western groups suggests a genetic predisposition[18-20].

Acquired SoVAs, in contrast, typically occur in older individuals, reflecting the additive effect of atherosclerosis or other risk factors such as infective endocarditis (IE), syphilis, vasculitis diseases, or trauma[21,22]. These aneurysms originate from the right coronary sinus in up to 90 of cases, followed by the noncoronary sinus (10%-25%) and the left sinus (< 5%)[3,23-25]. There is a significant increase in morbidity and mortality if ruptured SoVA occurs and remains untreated, owing to 1-year life expectancy[26].

ETIOLOGY AND RISK FACTORS

As mentioned above, SoVAs can be congenital or acquired[27]. Congenital SoVAs develop due to the absence of elastic lamina in the wall of the affected sinus, leading to an enlargement of the aortic root between the sinotubular ridge and the aortic valve annulus[28,29]. These aneurysms are frequently associated with other congenital heart anomalies such as BAV, VSD, and PS[30-32]. In fact, VSDs are present in up to 60% of cases[33]. Other associations include coarctation of the aorta, aortic insufficiency, atrial septal defect (ASD), and other rare coronary artery anomalies[34,35]. Aneurysmal dilatation of the sinus of Valsalva can occur due to connective tissue weakness in disorders such as Marfan syndrome, Ehler-Danlos syndrome, and other connective tissue diseases[36,37].

Acquired SoVAs, in contrast, occur due to several factors that diminish the strength of the aortic wall over time and are similarly associated with connective tissue pathologies[38-40]. Chronic changes of atherosclerosis leading to cystic media necrosis can weaken the intimal layer of the aorta, leading to SoVAs[41]. Infectious etiologies are well-known risk factors for the aneurysm, which include syphilis, tuberculosis, and IE[42]. Additionally, inflammatory conditions that damage the proximal aorta, including inflammatory aortitis and Takayasu arteritis, have been implicated as causes of SoVA[43]. Chest trauma and iatrogenic injury during aortic valve replacement surgery have also been reported as secondary mechanisms of acquired SoVA[43-45].

PATHOPHYSIOLOGY

The pathophysiology of SoVA commonly occurs due to a complex interplay of physiological and anatomical factors, which leads to the creation and potential rupture of the aneurysm[5,46]. SoVAs occur at the three dilated sections of the aortic root area between the aortic valve annulus and the sinotubular junction[47]. These sections are termed the sinuses of Valsalva, which are normally reinforced by elastic lamina, which a thick fenestrated layer of elastin that provides structural integrity to the aortic wall[48]. The lack or defect in the elastic lamina at the sinuses, particularly at the junction of the aortic media and the annulus fibrosus, leads to the formation of SoVAs[49]. In congenital cases, the anomalous development of the bulbus cordis during embryogenesis results in a structurally weakened aortic wall, giving rise to aneurysmal dilatation[50]. Congenital SoVAs are commonly associated with other heart defects such as BAV, VSDs, ASDs, and PS[50,51].

Acquired SoVAs occur due to chronic degenerative changes of the aortic wall[52]. These changes arise due to several factors, including atherosclerosis, connective tissue disorders, and aging, leading to progressive weakness and an increased risk of aneurysmal formation[51-53]. Infectious etiologies such as IE and syphilis lead to inflammation and scarring of the aortic wall, increasing susceptibility to aneurysm formation[54,55]. Similarly, inflammatory conditions such as vasculitis can cause chronic inflammation and structural changes, leading to SoVAs[56]. Complications from cardiac surgeries and trauma can lead to physical damage to the aortic wall, which predisposes to the formation of aneurysms and rupture[57]. The aortic root is predisposed to massive hemodynamic stress due to high-pressure blood flow from the left ventricle. This stress is more pronounced at the sinuses of Valsalva, where the aortic valve cusps attach. The absence of the elastic lamina or prolonged stress in this area significantly increases the risk of aneurysm formation and rupture[58].

CLINICAL IMPLICATIONS

The most feared complication of SoVA is rupture[56-58]. These aneurysms typically enlarge over time, which leads to thin wall rupture, causing blood to spread to the nearby pericardial space or adjacent cardiac chambers, leading to heart failure and hemodynamic instability[59]. Depending on the aneurysm’s physiologic location and function, it can present significant clinical consequences in both the rupture and unruptured state. Rupture of the right and noncoronary sinuses commonly results in communication between the right ventricular outflow tract and the aorta or the right atrium and the aorta[60,61]. This rupture, as a result, is susceptible to creating left-to-right shunts, which can lead to right-sided heart failure and right ventricular overload[60-62]. In contrast, rupture of a left SoVA is clinically less significant. This commonly results in communication to the left ventricular outflow tract and the left atrium[63].

Ruptures commonly occur between 20 and 40 years, with occasional outliers in late adulthood and early infancy[64]. In conjunction with the size and location, the speed at which rupture occurs is the major determinant of prognosis[65]. The right ventricle is the most common location of rupture, followed by the right atrium[66]. Historically, rupture across the interventricular septum has been associated with left ventricular outflow tract obstruction[65-67].

The size of SoVAs also has severe implications on clinical outcomes. Large SoVAs serve as a nest for thrombus formation[68]. Major coronary arteries have been occluded by SoVAs with thrombus formation, leading to ischemic heart disease. SoVAs in both the ruptured and unruptured states can be complicated by aortic regurgitation (AR), resulting in volume overload and heart failure[69]. AR as a complication occurs in up to 50% of patients with SoVAs[8,70]. For this reason, aortic valve replacement is usually done in conjunction with operative repair of the aneurysm at the time of surgery[71,72].

HISTORY AND PHYSICAL EXAMINATION

The clinical history of patients with SoVA is highly dependent upon whether the aneurysm is ruptured or unruptured. Patients with unruptured aneurysms are typically asymptomatic. The condition is frequently discovered incidentally in these patients while undergoing imaging for other reasons[73,74]. Symptomatic patients commonly express chest pain, dyspnea, and palpitations[75]. In cases where SoVA has ruptured, the history may include severe symptoms such as sudden onset chest pain, syncope, and severe shortness of breath. Patients may also report a history of syphilis, IE, cardiac surgery, and any other condition that predisposes them to SoVAs[76].

Physical examination is usually clinically unremarkable in asymptomatic patients. Patients with ruptured SoVAs typically have key examination findings such as murmurs. Diastolic murmurs indicate classic AR due to the aneurysm’s effect on the aortic valve[77]. Continuous murmurs can be heard if communication exists between the aorta and the right atrium or ventricle[78]. In cases of acute rupture, additional objective findings may include hypotension, hypoxia, and tachycardia.

DIAGNOSIS

In conjunction with physical examination, the diagnosis (Figure 1) of SoVAs usually requires imaging. These imaging modalities are as follows (Table 1).

Figure 1 Proposed diagnostic algorithm for the assessment of suspected sinus of Valsalva aneurysm. Transthoracic echocardiogram is first line, followed by transesophageal echocardiogram if findings are not diagnostic or equivocal for the aneurysm. Cardiac computed tomography (CT) or magnetic resonance imaging (MRI) is used for further assessment after confirmation of diagnosis on echocardiography. MRI has a higher temporal resolution than CT and offers excellent soft tissue contrast and anatomical delineation. As such, MRI is preferred over CT for concurrent valvular assessment and flow information. TTE: Transthoracic echocardiogram; VSD: Ventricular septal defect; ASD: Atrial septal defect; SoVA: Sinus of Valsalva aneurysm; TEE: Transesophageal echocardiogram; CT: Computed tomography; MRI: Magnetic resonance imaging.

Table 1 Comparison table of noninvasive imaging modalities used in the diagnosis and assessment of sinus of Valsalva aneurysms.

Imaging modalities	General information	Strengths	Limitations
TTE	The first imaging modality of choice for diagnosis of SoVA	Possess > 90% accuracy for detecting SoVA. It is additionally safe, cost-effective, portable, and more widely available	Can sometimes incorrectly detect rupture site
TEE	Required as additional imaging in up to 25% of cases to further characterize the anatomy of the sinuses and their surrounding structures	Possesses better acoustic window and higher resolution, which facilitates more accurate characterization of the aneurysm and its surrounding structures	Contraindicated in patients with esophageal disease including known stricture, varices, diverticula, or tumors
ECG-gated MDCT	An acquisition technique that triggers a scan during a particular portion of the cardiac cycle	Provides high spatial resolution, elimination of motion artifacts, and improved temporal resolution in the nonemergent setting. Additionally, gated CT’s ability to obtain multiplanar reformations provides superior anatomic delineation and can simultaneously assess the coronary arteries	More cost prohibitive. Additionally, retrospective ECG gating is needed to assess ventricular function and valvular motion, which carries a high radiation burden
Cardiac MRI	Plays an important role in SoVA assessment and is particularly important in the assessment of biventricular function	Gold standard imaging technique for SoVA due to its lack of ionizing radiation, better temporal resolution, ability to quantify ventricular function and aortic regurgitant fraction, and provides an assessment of wall motion abnormalities	More cost prohibitive

TTE: Transthoracic echocardiogram; SoVA: Sinus of Valsalva aneurysm; TEE: Transesophageal echocardiogram; ECG-gated MDCT: Electrocardiographic-gated multi detector computed tomography; CT: Computed tomography; ECG: Electrocardiogram; MRI: Magnetic resonance imaging.

Echocardiography

Echocardiography has been the traditional first-line imaging study to detect SoVAs[79,80]. A transthoracic echocardiogram is routinely performed first in cases of suspected SoVAs, although more commonly obtained for other reasons, such as heart failure exacerbation. This imaging modality can identify the aneurysm, visualize the aortic root, and detect associated anomalies such as an ASD, VSD, or a BAV[81]. For further investigation on transthoracic echocardiogram findings, a transesophageal echocardiogram (TEE) is usually performed, which provides a more detailed anatomical delineation of the aneurysm’s origin, which commonly appears on two-dimensional imaging as a thin-walled mobile structure that is circular in the short axis[82-84]. This structure commonly protrudes from above the plane of the coronary artery origins into an adjacent cardiac chamber, which produces a classical appearance known as a “windsock” deformity with enlargement during systole[84,85].

TEE also allows physicians to observe the filling of the aneurysm with color flow Doppler[86]. The additional use of contrast may help differentiate ruptured vs unruptured aneurysms and aid in visualizing the left-to-right shunt[86,87]. Spectral Doppler allows quantification of flow velocity and direction, where rupture into a cardiac chamber with subsequent shunting commonly yields a constant flow from the aorta to the lower pressure chambers through systole and diastole[88]. It is essential to recognize this pattern as it allows differentiation from other intracardiac shunts, such as VSDs[88,89].

Computed tomography

Cardiac computed tomography (CT) offers high-resolution images of the sinuses of Valsalva and provides quality images of the aorta[90]. This modality can delineate the morphology and size of the aneurysm and serve as a valuable tool for assessing cardiac and vascular structures in preparation for surgery[90,91]. Newer cardiac CT imaging, such as electrocardiogram gated angiography CT, can provide high-spatial resolution images of the aortic root[7]. This is an acquisition technique to obtain high-quality scans void of pulsation artifacts[7,92]. Electrocardiographic-gated CT offers several advantages to echocardiography in nonemergent situations. These include gaining an unrestricted field of view and obtaining multiplanar reformations to provide advanced anatomic delineation while assessing the coronary arteries[93,94]. Cardiac CT still possesses lower temporal resolution than magnetic resonance imaging (MRI) and cannot provide flow information, making CT inferior to MRI for valvular assessment[95].

MRI

MRI can provide a comprehensive assessment of cardiac morphology and is the gold standard technique for the evaluation of biventricular function[96]. It is considered the imaging study of choice, particularly in patients with infectious etiology, as a cause[96,97]. The saccular aneurysm can often be seen arising from one of the sinuses and protruding into an adjacent cardiac chamber. MRI has a higher temporal resolution than CT and offers excellent soft tissue contrast and anatomical delineation[98]. When used with multiplanar sequencing, it can further evaluate intracardiac shunts in ruptured SoVAs[99]. Although considered the gold standard for diagnosis, it is not required in cases where other imaging studies have already given the pertinent anatomic and physiologic details in conjunction with the diagnosis.

Cardiac catheterization

Angiography is not commonly used to diagnose SoVAs; however, it can provide detailed images of the coronary arteries and the aortic root[95]. Catheterization is particularly useful in patients with a planned surgical intervention and may aid the assessment of the hemodynamic impact of the aneurysm[95]. Patients who are at intermediate or high risk for coronary artery disease commonly undergo angiography to assess possible bypass grafting at the time of diagnosis[100,101].

MANAGEMENT

Medical management

For unruptured SoVAs, medical management is a temporary option for patients until definitive surgical intervention is possible. Medical therapy alone is insufficient as the optimal treatment for unruptured SoVAs. Management includes a serial echocardiogram to assess aneurysm morphology and size. In addition, blood pressure control is essential. Medications such as beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers should be used to lower blood pressure to the normal range and reduce aortic wall stress[102]. Patients should also be advised to limit activities that may increase intrathoracic pressure and precipitate rupture, such as heavy lifting and strenuous exercises[103]. In cases of acute rupture, medical stabilization with intravenous fluids and blood pressure support should be administered while managing heart failure or shock symptoms until surgical repair can be done.

Surgical management

Surgical repair is recommended for both ruptured SoVAs and SoVAs with associated intracardiac abnormalities such as VSD, PS, or significant AR[5,104,105]. Surgical intervention should also be considered for large SoVAs and patients with symptomatic unruptured aneurysms[106]. The main goal of repair is to prevent rupture and restore normal aortic and cardiac function. Although specific guidelines regarding SoVA repair are yet to be established, it is generally accepted to follow the abdominal aortic aneurysm algorithm[107]. According to the 2010 American Guidelines on Thoracic Aortic Disease, surgical repair should be considered in those with aneurysms > 5.5 cm, > 5 cm in patients with BAVs, > 4.5 cm in the setting of connective tissue disease, or a growth rate of more than 0.5 cm per year[108].

All surgical repairs are done with cardiopulmonary bypass and cardioplegic arrest[109]. Several operative approaches are available. However, the choice is determined by the size of the aneurysm, aortic valvular pathology such as aortic insufficiency, the cardiac chamber involved, and the associated intracardiac anomaly such as a VSD[110,111]. The primary operative approaches include through the cardiac chamber where the aneurysm has ruptured, through the aortic root via an aortotomy, or a combination of both, including an aortotomy and an incision into the involved cardiac chamber. Closure techniques include primary and patch closure[112]. Primary closure is commonly used for the repair of small SoVAs, while patch closure is preferred in the repair of larger SoVAs[112,113]. The use of primary closure in large SoVAs can distort the aortic sinus, resulting in valve incompetence or excessive tissue tension at the site of repair, which may increase the risk of recurrent rupture in the future[112-114]. Surgical repair overall has an operative mortality rate of up to 3.6%, with survival rates of close to 90% at 15 years[5,112].

TCC

TCC is a newer minimally invasive technique that is used to treat both ruptured and unruptured SoVAs[115]. This is an alternative approach to open heart surgery and is particularly useful in patients who are high-risk surgical candidates, including those who are older and patients with multiple comorbidities[115,116]. Clinical indications for TCC include both symptomatic and asymptomatic unruptured aneurysm and ruptured SoVAs causing heart failure or hemodynamic instability[115-117].

TCC offers several advantages, including avoiding open heart surgery, especially in high-risk surgical candidates. This avoidance reduces surgical risk and shortens hospital length and recovery time[118]. Several studies have demonstrated high success rates for TCC, resulting in effective aneurysm occlusion and relief of symptoms[118,119]. Complications such as residual shunt or embolization and device malposition are relatively low and can be treated with rapid intervention[120,121]. With the advancements in device technology and procedural techniques, TCC is becoming increasingly preferred over the traditional surgical approaches in managing SoVA. A comparison of treatment approaches with their respective advantages and disadvantages can be seen in Table 2.

Table 2 Comparison table of treatment options for sinus of Valsalva aneurysms.

Interventions	Recommendations	Advantages	Disadvantages
Medical management	Insufficient for definitive treatment. Blood pressure control with antihypertensives such as angiotensin-converting enzyme inhibitors, beta-blockers, or calcium channel blockers to reduce aortic wall stress should be used as a temporary measure until definitive surgical repair or transcatheter closure can be done	Reduces the chances of rupture for cases of unruptured SoVAs	Not definitive treatment
Surgical repair	Surgery remains the definitive treatment for SoVAs. Recommended for symptomatic, large, or rapidly progressive aneurysms and all ruptured aneurysms. The 2010 American Guidelines for Thoracic Aortic Disease recommend considering surgical repair for aneurysms greater than 5.5 cm, greater than 5 cm in patients with BAVs, greater than 4.5 cm in the setting of connective tissue disease, or a yearly growth rate that exceeds 0.5 cm	Can address concurrent cardiac issues such as VSDs or aortic valve dysfunction	Higher risk for complications such as bleeding, infection, or heart failure. Additionally, surgical repair prolongs hospital stay and recovery times compared to TCC
Transcatheter closure	Emerging minimally invasive technique used to treat both ruptured and unruptured aneurysms	Advantages include reduced surgical risks, avoiding heart surgery, and shortened hospital length and recovery times	Has potential complications such as residual shunt, embolization, or device malposition, which are generally manageable

SoVA: Sinus of Valsalva aneurysm; BAVs: Bicuspid aortic valve; VSDs: Ventricular septal defects; TCC: Transcatheter closure.

Patient selection criteria for TCC

Patient selection criteria should be carefully considered prior to intervention for SoVA. Xiao et al[122] consider patients to be candidates for TCC if they meet the following: A bodyweight exceeding 10 kg, if the right or non-coronary sinus is the origin of the defect rupturing into the right atrium or ventricle, if the defect size is < 10 mm, if the ruptured SoVA does not involve the aortic valve has > 7 mm distance from the annulus of the aortic valve, if surgery is needed in the absence of other cardiac defects, and if a gap of > 5 mm exists between the ostium of the right coronary sinus and the ruptured site. Liu et al[123] also suggested that patients with ruptured SoVAs with a European System for Cardiac Operative Risk Evaluation II score greater than 20% would benefit from catheter closure. Overall, indications for TCC vs surgery remain a topic of debate among the medical community. Further studies are needed to validate the inclusion and contraindications for patients with ruptured SoVAs.

TCC vs surgical outcomes

Since the initial case of TCC repair of a ruptured SoVA in 1994, evolving evidence, mostly in the form of case series and reports, has indicated the effectiveness of catheter closure as a suitable alternative to surgery[124-126]. TEE is valuable during the intervention because it provides real-time visualization of cardiac structures, particularly the aortic valve[82-88]. A systematic review by Ayati et al[120] revealed a post-interventional mortality of only 0.5% from a cohort of 407 patients who underwent TCC for ruptured SoVAs. In this review, 12% of patients developed complications, most notably from residual shunts (1.7%), new onset aortic insufficiency (1.5%), and rupture recurrence (1.5%). The study ultimately concluded that while TCC is a valuable alternative to surgery, precise patient selection is mandatory as surgery still remains the first-line treatment option for patients with ruptured SoVA and accompanied heart defects, arrhythmias, infections, or outflow tract obstruction. This post-operative mortality is notably lower compared to the surgical mortality mentioned by Sarikaya et al[112] in their retrospective review. However, more systemic reviews and meta-analyses of larger patient cohorts are needed to clarify the mortality benefit between the two treatment approaches.

CONCLUSION

The diagnosis of SoVA requires a combination of history, physical examination, and imaging. The first line imaging study includes an echocardiogram to visualize the aortic root, identifying the aneurysm and any associated intracardiac abnormality. Additionally, cardiac studies such as CT and MRI can provide more precise information on the anatomic delineation of the aneurysm and its surrounding structures. Definite treatment of SoVAs includes surgery. However, TCC is an emerging technique used in managing both ruptured and unruptured SoVAs and is now increasingly preferred over traditional surgical approaches due to the reduction in surgical risk, shortened hospital course, and decreased recovery time.

Although inclusion criteria for TCC exist regarding the treatment of SoVAs, there are no evidence-based clinical guidelines that provide a census within the medical community. Therefore, clinicians should ultimately decide on treatment based on each clinical scenario. More research is needed to validate the indications and contraindications of TCC in patients with ruptured SoVAs. Larger studies are also needed to further assess mortality, complication rates, and recovery time between TCC and traditional surgery for SoVAs.