INTERNATIONAL JOURNAL OF CARDIOLOGY AND CARDIOVASCULAR MEDICINE (ISSN:2517-570X)

Among congenital cardiac valve malformations, the quadricuspid aortic valve is the rarest condition and it has been associated to a spectrum of abnormalities related to molecular genetics, cardiovascular and biomechanical physiology. This review presents a clinical report of a 58-year-old man presenting a significant increase in the cardiac area, due to enlargement of the left chambers and atrial fibrillation rhythm admitted due to a progressive dyspnea on exertion for 2 years. A quadricuspid aortic valve was observed during transthoracic echocardiogram (TTE). No other abnormalities were observed. Because of the presence of heart failure associated with atrial fibrillation, it was prescribed sodium warfarin and indicated aortic valve replacement. The aortic quadricuspid valve requires a precise diagnosis and appropriate treatment, such as valve replacement and the tricuspidalization of the aortic valve.

Echocardiography; Aortic valve; Aortic valve insufficiency

Among congenital cardiac valve malformations, aortic valve diseases are relatively common, such as the bicuspid aortic valve, with an incidence of 0.5 - 1.2% of the population, and the unicuspid type, the second most common type[1]. The quadricuspid aortic valve, considered rare, occurs in an incidence between 0.008 and 0.043%[2-4]. It is known that during the fifth week, active proliferation of mesenchymal cells in the cardiac bulb walls results in the formation of bulbar ridges that are continuous with the artery trunk ridges. Both ridges are derived mainly from the neural crest mesenchyme. As this occurs, the bulbar and trunk crests undergo a 180-degree spiral rotation, caused in part by blood flow from the ventricles, resulting in the formation of a spiral aorticopulmonary septum that divides the heart bulb and the arterial trunk into two arterial channels, the ascending aorta and the pulmonary trunk. When the division of the arterial trunk is almost complete, the semilunar valves begin to develop from three buds of subendocardial tissue around the aortic and pulmonary trunk holes. Heart precursor neural crest cells also contribute to this tissue. These buds are cavitated and reshaped to form three thin-walled cusps [5].

Krishnamurthy et al. [6] state that aortic valve malformations are associated with a spectrum of abnormalities related to molecular genetics, cardiovascular and biomechanical physiology.Similarly, Toomer et al. [7] support the molecular genetics cause of the disease. This statement is further supported by clinical findings in patients with complex congenital diseases associated with cilia interruption known as “ciliopathies”. In this sense, Toomer et al. [7] describe three new aspects of cilia during embryonic development and suggest that cilia play a role in suppressing differentiation of aortic valve mesenchymal cells and further support a model that cilia dictate the temporal activation of extracellular matrix differentiation. Due to the indispensable role of cilia in regulating various growth factor signaling pathways, these structures may play a role in aortic valve disease in humans.The aim of this review was to show a recent case of quadricuspid aortic valve and discuss the rarity of this condition, emphasizing the diagnosis and the most indicated treatments. 

A 58-year-old man goes to a cardiac clinic complaining of progressive dyspnea on exertion for 2 years, bringing with him a chest x-ray taken in an emergency unit, showing a significant increase in the cardiac area, due to enlargement of the left chambers. He has systemic arterial hypertension for over 10 years, currently using losartana, carvedilol and amlodipine. Also reported being a smoker 40 years ago. He denied any history of diabetes, rheumatic diseases, hyperlipidemia, thyroid and hematologic disorders. At the initial examination the blood pressure was 130/40mmHg, the pulse was regular with 67 beats per minute and breathing 14 times per minute. On inspection and palpation, he presented ictus cordis shifted left and down, filling 4 digital pulps, and diastolic thrill. Cardiac auscultation showed a decreasing aspiration grade IV / VI diastolic murmur, more audible at the right sternal border (aortic focus), with irradiation to accessory aortic focus. A 12-lead electrocardiogram showed atrial fibrillation rhythm, with a heart rate of 62 beats per minute, and signs of strain-left ventricular overload (Cornell and Sokolow-Lyon criteria). Due to the findings of the physical examination and the electrocardiogram, a transthoracic echocardiogram (TTE) was requested. In the long axis parasternal window it was possible to notice a slight thickening of the cusps at closure, as well as a large color Doppler aortic regurgitation. Still in the parasternal window, but in the short axis, it was already possible to observe the presence of four cusps, with poor coaptation with each other, being the probable cause of aortic insufficiency. Figure 1 shows the aortic valve with the presence of four symmetrically arranged cusps at the end of diastole. Poor valve coaptation is noted, causing the appearance of a large regurgitation orifice.

The view shown in Figure 2 confirms the presence of four cusps, since there was no appearance of rafes that could indicate cusp fusion. In addition, TTE demonstrated eccentric myocardial hypertrophy (with LV diastolic diameter of 62mm, myocardial mass index of 135g/ m² and relative thickness of 0.39), with an ejection fraction of 48% according to Simpson’s method. Besides significant biatrial increase, with moderate mitral and tricuspid regurgitation and pulmonary artery systolic pressure of 43mmHg. With poor coaptation of the aortic valve cusps and the formation of a large regurgitant orifice, the patient developed severe aortic regurgitation, as can be seen in Figure 3. No other abnormalities were observed. Because of the presence of heart failure associated with atrial fibrillation, with the presence of two points in the CHADS2VASc score, it was decided to start the use of sodium warfarin and indicated aortic valve replacement, in accordance with current guidelines.

The aortic quadricuspid valve is a rare condition that affects 0.006% to 0.017% of patients who underwent echocardiography [8]. Middle-aged people are usually affected and are described in seven subtypes, classified as a-g [9,10]. In the 30-year interval (1988- 2018), 280000 echocardiographic examinations were performed on patients at Keio University Hospital and only 8 patients had aortic quadricuspid valve[11]. Aortic regurgitation is present in 74.7% of cases, and may also be associated with stenosis, in 8.4% of quadricuspid aortic valve cases, 0.7% only stenosis and 16.2% of normal function of the quadricuspid aortic valve3. Studies show that aortic and quadricuspid valve dilation together have low incidence[12]. However, reports show that 42% of patients undergoing surgery due to the presence of the quadricuspid aortic valve had an ascending aorta diameter ≥ 4 cm and 53.8% of these patients had to have their ascending aorta repaired[13]. Tsang, et al. [8] reported that aortic dilatation was present in 29% of patients with quadricuspid aortic valve, thus, of these patients, 36% dilated in the Aortic root, 36% tubular diastation of the Aorta. In addition, of these cases of aortic dilation, 79% are considered mild and 21% were moderate. Aortic ring rupture may be associated with aortic root dilation [14].

Even though the aortic quadricuspid valve is considered an isolated disease, it may be present concomitantly with other anomalies. On average, 25% of patients had other problems such as coronary artery ostium abnormalities, atrial or interventricular communication, tetralogy of Fallot, persistent artery duct, mitral valve insufficiency or prolapse, nonobstructive hypertrophic cardiomyopathy, subaortic fibromuscular stenosis and transposition large vessels[15,16]. In the presence of raphes, blood returns and, over time, leads to valve degeneration11. Due to different forms of raphes, Tsugo et al. [11] classified the different raphes based on their forms, A – 0 raphe, B – 1 raphe, C – 2 raphes (symmetric location), D – 2 raphes (asymmetric location), E – 3 raphes and F – 4 raphesz. This classification of the quadricuspid aortic valve system helps in prescribing prognosis. Nakamura et al. [17] based on the position of the supernumerary cusp, suggested the classification of the four types: type I - supernumerary cusp between left and right cusp, type II - supernumerary cusp between right and non-coronary cusp, type III - cusp supernumerary cusp between left and non-coronary cusp, type IV - unidentified supernumerary cusp due to equal sizes. Another classification, previously cited, was elaborated by Hurwitz & Roberts (1973)[10], in which seven groups are named: Type A - normal quadricuspid, Type B - three equal and one smaller cusp, also considered the most common, type C - two equal cusps. larger and two smaller equal cusps, type D - one large cusp, two intermediate cusps and one small cusp, type E - three equal cusps and one smaller cusp, type F - two smaller equal cusps and two unequal smaller cusps, type G - four uneven cusps [18].

The formation of the semilunar valves occurs around the fifth week of development, in addition to the formation of the aorticopulmonary septum. The development of the quadricuspid aortic valve is still unclear, deviation of fusion in semilunar valve formation or aorticopulmonary septal formation may interfere with valve cusp formation, just as inflammatory reactions also interfere with normal aortic valve development [8,14,15]. The clinical manifestations of patients with this anomaly occur according to the associated problems and may be asymptomatic for most of their lives. Palpitation, foot edema, syncope, shortness of breath and fatigue, pain in the precordial region are some of the relevant clinical manifestations in patients with quadricuspid aortic valve. The main symptom is congestive heart failure[14,19]. Accurate and assertive diagnosis is of paramount importance in determining the course of action, use of echocardiography, computed tomography or cardiac magnetic resonance imaging are materials used for the diagnosis of quadricuspid aortic valve [19,20]. A study by Janssens et al. [21] showed that the largest number of diagnoses were made by echocardiography, followed by necropsy, surgery and angiography. The visualization of the diastolic aortic valve forms the lines between the cusps are similar to an “X” in the case of the quadricuspid aortic valve, unlike the “Y” formed by the normal tricuspid aortic valve 2. Color Doppler confirms aortic regurgitation caused by incorrect valve closure[15].

Computed tomography shows us very precisely the state of the tricuspid aortic valve, the most important being the location of the coronary ostium, the size of the valve and the condition of the coronary arteries. Cardiac magnetic resonance also shows us important data such as valve morphology, aortic regurgitation volume and leaflet calcification[22]. The risk of infectious endocarditis is relatively low, present in only 1.4% of quadricuspid aortic valve cases, with the numerical cusp having the highest risk of developing this type of infection[23]. Some authors indicate the use of prophylactic antibiotics, but others indicate only when there is aortic regurgitation with asymmetric supernumerary cusp, except in patients with mild aortic regurgitation and symmetrical cusps [16,23]. According to the American College of Cardiology / American Heart Association (ACC / AHA) in 2008, it does not recommend prophylactic antibiotic treatment in patients without evidence of active infectious endocarditis [24]. Surgery is indicated when there is severe aortic regurgitation, aortic stenosis, or other dysfunctions with left coronary ostium occlusion8. In young patients valve replacement may not be the best choice due to risks due to valve exposure such as thromboembolism, valve prosthesis degeneration and endocarditis [25]. What has been done most often is tricuspidalization of the aortic valve along with resection of subaortic stenosis if appropriate. Authors have described the techniques used according to their corrections, Langer et al. [26] repaired the quadricuspid aortic valve by detaching the rudimentary commissures, approximation of adjacent cusps and enlargement of the new cusp. Another author used the pericardium augmentation, making a triangular resection in the cusp tissue [25]. Another technique was described by Williams, et al. [27], which included detachment of the abnormal commissure, after excision of thickened tissue, approaching leaflets and subcommissural annuloplasty for quadricuspid aortic valve repair. Song et al. [28] reconstructed the pericardial leaflet, reduced the sinotubular junction, and performed commissure coaptation suture. Although the incidence of postoperative complications is low, researchers have reported cases that included progressive aortic regurgitation, cardiac arrest, and transient ischemia. The prognosis of patients with quadricuspid aortic valve is good, 89.9% of survival after five years and 84.9% of survival after 10 years [8].

Tricuspidization with bovine pericardium had significantly improved hemodynamics in all patients undergoing surgical procedures to correct the quadricuspid aortic valve in the medium and long term (Song, 2014). In another study, aortic regurgitation and/or aortic valve stenosis was present in 42.9% (3/7) of patients with quadricuspid aortic valve who underwent surgical repair. In contrast, only 8.7% (2/23) of patients undergoing aortic valve replacement surgery developed postoperative stenosis [29]. Besides all these findings, the cause of this malformation is still unclear and, as reported, surgery is still the most indicated treatment when there are severe conditions associated. 

The aortic quadricuspid valve is a rare condition that requires a precise diagnosis and appropriate treatment, such as valve replacement in severe conditions and the tricuspidalization of the aortic valve along with resection of subaortic stenosis using different techniques.

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