The normal aortic valve consists of three semilunar cusps: the right coronary cusp (RCC), left coronary cusp (LCC), and non-coronary cusp (NCC). In contrast, the bicuspid aortic valve (BAV) only has two semilunar cusps because of the fusion of the cusps, making it the most common congenital heart valve disease found in adults, occurring in approximately 0.5%-2% of the overall population [1]. The fusion of valve cushions during cardiac embryonic development is related to the formation of the BAV, and the fusion of underdeveloped cusps, known as raphe, is an aborted commissure during embryonic development [2].

BAV is classified into three types: fused, two-sinus, and partial-fusion BAV. The fused type is the most common (approximately 90%-95%), characterized by fusion of two cusps within three aortic sinuses, resulting in two functional cusps of unequal size and shape. The two-sinus type is less common (approximately 5%-7%), with two aortic sinuses and two cusps of nearly equal size positioned 180° apart. The prevalence of this recently recognized partial-fusion BAV is unknown. The appearance of the partial-fusion BAV is that of a typical tricuspid aortic valve: less than 50% cusp fusion is noted at the base of a commissure, forming a small “mini-raphe” (Fig. 1) [3].

BAV is diagnosed through imaging tests, such as echocardiography, including Doppler examination, and is a significant genetic component that requires screening of first-degree relatives, as outlined in the American Heart Association/American College of Cardiology 2022 guidelines [4]. Initially, it may be asymptomatic; however, over time, various complications such as dystrophic calcification, infectious endocarditis, aortic stenosis, aortic regurgitation, and aortic dissection may arise, leading to symptoms [5]. A proportion of individuals with BAV still experience sudden cardiac death (SCD), and for some, SCD can be the first presentation [6]. In the case of SCD, histological examination of the heart, including the heart valves, is limited in clinical practice; however, it is believed to have forensic significance, as a detailed clinicopathological examination is possible through forensic autopsy. Accordingly, we report a case of SCD as the first clinical presentation of BAV, with comprehensive postmortem studies, including pathological examinations.

The deceased, a 63-year-old woman, was working at a construction site at approximately 7:00 AM, pushing a cart from behind to move materials; at 7:11 AM, she suddenly fell forward and collapsed for an unknown reason. A colleague who pulled the cart called 119. Upon arrival of emergency services at 7:18 AM, she was unconscious with a blood pressure of 0/0 mmHg, heart rate of 38 bpm, respiratory rate of 9 bpm, and abnormal breathing patterns. When an automated external defibrillator was applied, the initial rhythm was identified as pulseless electrical activity. Despite continued cardiopulmonary resuscitation during transport and at the hospital, the patient died on the same day at 8:12 AM.

A review of the health insurance medical records from January 24, 2017, to August 19, 2024, indicates that the deceased had no history of diagnosis or treatment for BAV and no significant medical history other than hypertension. According to statements from the family, the deceased did not smoke or drink alcohol, and with a height of 153 cm and a weight of 55 kg, the body mass index was 23.5, which does not fall into the obesity category.

An autopsy was conducted one day after death. External examination confirmed injuries to the forehead and nose area consistent with a fall without proper protection due to sudden unconsciousness, as well as a few petechiae in the conjunctivae of the eyelids. Apart from the medical treatment marks, no significant findings that could have led to death were observed throughout the body.

Internal examination revealed no specific injuries other than those resulting from medical procedures, such as cardiopulmonary resuscitation. The heart weighed 436 g, and the mean thickness of the right ventricle free wall was 3 mm, the left ventricle free wall was 15 mm, and the mean ventricular septal thickness was 16 mm, which were hypertrophied. The blood within the cardiac chambers was fluidic. Atherosclerosis was observed with approximately 20% and 40% occlusion of the lumens in the left anterior descending branch and right coronary artery, respectively. The aortic valve was composed of two cusps (LCC and RCC) and was accompanied by severe calcification (Fig. 2A). The angle formed by the two cusps was approximately 180°, corresponding to the latero-lateral phenotype of congenital two-sinus BAV without raphe.

Additionally, the circumference of the aortic valve was approximately 6.5 cm, and the circumference at the beginning of the aorta was approximately 11 cm, indicating dilation (Fig. 2B). No specific findings other than congestion were observed in other organs.

Histopathological examination revealed interstitial fibrosis and hypertrophy of cardiomyocytes in the myocardium and multiple calcified nodules in the aortic valve. Calcification was observed not only in the cusps of the valve but also in the sinus wall of the aorta, and some segments of the ascending aortic wall connected to the aortic valve were thinned (Fig. 3A). Additionally, interstitial fibrosis was noted in a downward pattern toward the interventricular septum at the hinge area of the valve (the area where the cusp was attached to the aortic wall) (Fig. 3B, C). In the thinned ascending aortic wall, the medial degeneration was noted, and the elasticity was confirmed to be lost (Fig. 3D).

Postmortem computed tomography (PMCT) also revealed calcification of the aortic valve and dilation of the ascending aorta (Fig. 4). The average PMCT density of the aortic valve calcified nodule was 613.0 Hounsfield units (HU), which was higher than that of the adjacent vertebral body (531.5 HU). In addition, the diameter of the ascending aorta was 41 mm, indicating dilatation.

In the toxicology tests, the antihypertensive drug and the anti-inflammatory analgesic were detected within therapeutic concentration ranges, and the ethyl alcohol concentration in the peripheral blood was less than 0.010%, with no other signs of intoxication.

In summary, the cause of death was SCD due to BAV disease accompanied by calcification.

Calcification of the aortic valve is a common complication of BAV [5]. In 1866, Peacock [7] discovered that calcific stenosis is likely to occur in BAV. Mechanical stress and tensile strength applied to the valve leaflets are the major factors that induce cardiac valve calcification. In particular, in the case of BAV, structural defects significantly increase the burden on the valve, promoting damage. In autopsy, distinguish congenital BAV from acquired fusion secondary to calcification is often necessary. In congenital cases, the raphe (pseudo-commissure) is attached lower within the aortic root than the true commissures. Additional distinguishing gross features include an obtuse angle between the fused cusps and the absence of a cleavage plane on the ventricular aspect, whereas acquired fusion typically shows an acute angle and a distinct cleavage plane [3]. Patients with BAV tend to develop calcific disease at an earlier age, with symptoms generally appearing at approximately the ages of 50-60 years. As the stress-strain relationship of BAV deviates from the normal range, this high tensile strength may contribute to the early onset and rapid disease progression [8]. When the aortic valve becomes calcified, it does not open well during left ventricular contraction, causing the heart to contract with a greater force to compensate. Consequently, the pressure exerted on the left ventricle increases, leading to left ventricular hypertrophy and hypertension. If this condition persists, it causes an imbalance between the oxygen demand and supply of the myocardium, resulting in interstitial fibrosis, increased stiffness, and myocardial necrosis. This leads to systolic and diastolic dysfunction, ultimately resulting in death [9,10].

The abnormal blood flow pattern associated with BAV also affects the aortic root and the ascending aorta, causing asymmetry and increased shear stress on the aortic wall. This mechanical stimulation leads to structural changes such as thinning and degeneration of elastic fibers and dysregulation of the extracellular matrix, ultimately weakening the aortic wall and causing dilation. In particular, the altered hemodynamics and intrinsic matrix abnormalities of the medial layer of the aorta promote the destruction of elastin and smooth muscle cells and the activation of matrix metalloproteinases. This activation can lead to serious complications such as aortic dilation (especially of the ascending aorta), aneurysm formation, and, in severe cases, aortic dissection [1].

The atrioventricular (AV) node is located just below the commissure between the NCC and RCC of the aortic valve at the apex of the Koch triangle in the right atrium. This area is adjacent to the membranous septum and is anatomically close to the subaortic region. The His bundle originates from the AV node, penetrates the membranous septum, and divides into left and right bundle branches. The left bundle branch descends to the surface beneath the interleaflet triangle between the NCC and RCC, traveling along the interventricular septum [11]. Calcification occurring in this adjacent area can damage the conduction system, potentially leading to a complete AV block and ventricular arrhythmia such as ventricular fibrillation, which are known causes of SCD. Several previous studies have reported that aortic valve calcification can cause complete AV block [12]. Yamauchi et al. [13] reported in a case of a 42-year-old man that calcification of the aortic valve causes inflammation by contact with the cardiac conduction system, resulting in complete AV block. Calcific aortic valve disease (CAVD) is characterized by thickening, fibrosis, and mineralization of the aortic valve leaflets [14]. However, in this case, the deceased exhibited calcification not only in the leaflets but also in the walls of the aortic sinus, showing a different pattern from that of typical CAVD. Additionally, a distribution pattern of interstitial fibrosis was observed spreading downward toward the interventricular septum at the hinge of the leaflets. This distribution pattern suggests anatomical continuity between the valvular hinge region and conduction pathways, potentially implicating the calcification-fibrosis complex in arrhythmogenic events. In summary, the unique histopathological distribution of calcification and fibrosis in this case, extending from the aortic valve hinge toward the interventricular septum, suggests an anatomical substrate for conduction system involvement, which may contribute to arrhythmogenic SCD in patients with undiagnosed BAV.

Additionally, BAV can lead to various complications. Park et al. [15] reported cases of patients with no prior medical history who died suddenly from rupture of a subvalvular aortic aneurysm with resultant hemopericardium with tamponade. As such, BAV can cause several complications, including infective endocarditis, aortic dilation and aneurysm, aortic stenosis, aortic regurgitation, and aortic dissection. The complications and prognosis can differ depending on the morphology. BAV without raphe has a lower incidence of aortic stenosis and regurgitation than other morphology with raphe [1]. However, as seen in the present case, even in patients with hypertension as the only underlying condition, sudden death can occur because of BAV without raphe, indicating that this disease requires careful attention. Nevertheless, research on the SCD rate and its association with SCD according to BAV type is considerably lacking. Morphological differences in BAV can affect not only the clinical course but also the mechanisms of death. Particularly, differences in the anatomical locations of calcification and fibrosis may influence conduction system damage, the occurrence of arrhythmias, and, consequently, the risk of SCD. Therefore, anatomical changes and accompanying pathological findings according to BAV morphology should be analyzed in the future to explore their relationship with the risk of sudden death. Additionally, examinations of the coronary arteries, myocardium, valve structure, and cardiac conduction system should not be neglected during autopsy.