A 37-year-old woman presented with worsening intermittent chest pain and dyspnea for 1 year and was admitted to our hospital. Interestingly, although the dyspnea was exertion-dependent, her chest pain heavily depended on the postural position as it worsened in the supine position but was alleviated by lying prone or sitting up and leaning forward. The patient had moderate anemia due to adenomyosis. She had no history of chest trauma, infective endocarditis, syphilis, tuberculosis, hypertension, diabetes, dyslipidemia, aortic aneurysm, or connective tissue disease. Her vital signs were as follows: body temperature 36.5  C, blood pressure 130/70 mmHg, pulse 75 beats/min, respiratory rate 20 breaths/min, and oxygen saturation 96% (indoor air). A physical examination revealed lip cyanosis (Figure 1A) and a diastolic murmur at the left third intercostal space was present. Respiratory and abdominal examinations revealed no abnormal findings. Written informed consent for publication was obtained from the patient.
A hematological evaluation showed a hemoglobin level of 73 g/L (microcytic hypochromic anemia), a white blood cell count of 4.59 x 109/L, and a platelet count of 143 x 109/L. Other laboratory data, including myocardial enzyme levels, NT pro-brain natriuretic peptide levels, coagulation function, and hepatic and renal function were normal. Electrocardiography showed sinus rhythm, obvious ST-segment elevation in the aVR, and depression in the II, III, aVF, and V3-V6 leads when she lay flat and had angina pectoris attacks (Figure 1B). However, when she sat up for a few minutes, her symptoms and ST segment abnormalities disappeared (Figure 1C). Echocardiography revealed large unruptured aneurysms in both the left (47 mm x 43 mm) and non-coronary (44 mm x 35 mm) sinuses (Figure 2A), along with an enlarged left ventricle (58 mm, Figure 2B), a dilated aortic root (52 mm, Figure 2C), a ventricular septal membranous aneurysm (19 mm x 16 mm, Figure 2D), severe aortic regurgitation (Figure 2E), right ventricular high pressure (pressure gradient 54 mmHg, Figure 2F), and decreased left ventricular systolic function (ejection fraction 51%). Coronary angiography showed ~90% pulsating stenosis of the left main coronary artery (LM) and ~80% pulsating stenosis of the proximal left circumflex artery (LCX), presumably caused by pulsation of the dilated left SVA under blood pressure (Supplementary Video S1). The aortic root was severely distorted when we attempted to intubate the coronary arteries. Non-obstructive atherosclerosis was observed in the right coronary artery (RCA). Cardiac computed tomography angiography (CCTA) clearly showed a large unruptured left SVA (Figure 3A), which was anatomically close to the LM (Figure 3B) and proximal LCX (Figure 3C), causing severe narrowing of the vessel lumens. The dilated left SVA upwardly squeezed the pulmonary trunk (Figure 3D) and accelerated the maximum pulmonary blood flow to 3.7 m/s. The dilated non-coronary SVA adjoined the right atrium without a crevasse (Figure 3A). The right coronary sinus was normal, and the RCA blood flow was smooth. The sagittal plane view showed dual unruptured left/non-coronary SVAs (Figure 3E). Three-dimensional reconstruction images showed the LM and LCX running along the epicardium of the left SVA, with severe narrowing of the LCX (Figure 3F). To rule out other etiologies, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, antidouble stranded DNA antibody, anti-neutrophil cytoplasmic antibody, lupus anticoagulant, T-spot, and syphilis serology tests were performed, but all were negative. Genetic testing revealed c.1781 C > G nonsense mutations in the FLNA gene. According to the American College of Medical Genetics and Genomics (ACMG) standard, FLNA c.1781 C > G was determined as a "likely pathogenic mutation" since it satisfied the criteria of both PVS1 (pathogenic very strong) and PM2 (pathogenic moderate).
On admission, we administered nitroglycerin, an oxygen mask, and metachysis to alleviate her symptoms. Three days later, the patient underwent surgical intervention, including aneurysm patch closure, coronary artery reconstruction, and aortic valve and aortic root replacement. Operative findings confirmed a dual unruptured Valsalva aneurysm of the left coronary and non-coronary sinuses (Figure 4). The right coronary sinus was normal. The modified Bentall procedure was performed using a 26 mm biological composite graft and a mechanical aortic valve (Carbomedics Inc., Austin, TX, United States). The LM artery was then re-implanted into the newly formed left coronary sinus. Unfortunately, the patient experienced cardiac arrest during the operation, and, despite receiving an emergency thoracotomy, the heart was unable to recover after surgery and she died.