Aortic Hypoplasia in Young Adult Patients with Sudden Intrinsic Cardiopulmonary Arrest: An Observational Study

Background: The leading cause of sudden cardiac death in adults over 40 is ischemic heart disease due to vascular atherosclerosis. In contrast, sudden cardiac death in adults younger than 40 (young adults) may be caused by aortic hypoplasia (AH). To date, few detailed studies of AH exist. This study evaluated AH patients in our hospital for sudden cardiopulmonary arrest in young adults. Methods: We selected young adult patients who transferred to our center with cardiopulmonary arrest status between April 2010 and March 2020. Their cause of death was supposed to be cardiac or unknown. In the chart review, sex, age, rate of computed tomography (CT) being performed, and outcome were described. For patients with CT being performed, we assessed the diameters of the aortic root, ascending, descending and abdominal aorta, and right femoral artery. Results: There were 1268 cardiopulmonary arrest cases during the study period. Thirteen young adults died of intrinsic diseases, such as sudden cardiac death or unknown cause of death. Twelve patients underwent CT scans, and eight (61.5%) had AH. Conclusions: For a decade, 61.5% of young adults who died of intrinsic diseases had AH. Further studies should be conducted to reveal AH’s clinical signicance in young adults.


Background
The leading cause of sudden cardiac death in adults over 40 is ischemic heart disease due to vascular atherosclerosis, especially in developed countries. In contrast, sudden cardiac death in adults under 40 (young adults) is often caused by congenital diseases, such as hypertrophic cardiomyopathy, congenital QT prolongation syndrome, and Brugada syndrome. Alternatively, aortic hypoplasia (AH) is a possible cause of sudden cardiac death in young adults. [1] From his approximately 3,000 forensic autopsies, Laurie found that AH has a diameter of less than 2 cm at the aorta's root in normal adults. [1,2] Laurie examined autopsies of 14 young adult patients who died suddenly and found aortic openings less than 2 cm in diameter, with no coronary artery anomalies or obstructive diseases, suggesting that hypoplasia of the aorta is the cause of death. [1,2,3] However, to date, few detailed studies of AH exist. This study evaluated the proportion of young adult patients with AH in sudden death at our institute.

Methods
This retrospective observational study was conducted at the tertiary emergency center in Japan. This study retrospectively examined and described the aortic root diameter of patients aged 18-40 with nontraumatic cardiopulmonary arrest. We searched all electronic medical records of our department and selected the young adult patients. They were transferred to our center with cardiopulmonary arrest status between April 2010 and March 2020. Of those, the patients whose cause of death was supposed to be cardiac or unknown were enrolled. Regarding the cause of death, we referred to the medical records and con rmed the death certi cate prepared by attending physicians, and reassessed their validity. Almost all patients received the autopsy imaging (Ai) of computed tomography (CT), which contributed to clarifying the cause of death. We determined outcomes based on chart review, sex, age, and CT scan results when available.
For patients who underwent CT, we assessed the diameter of the aortic root. Regarding this evaluation, we referred to a previous paper [1] and de ned AH with a diameter of less than 2 cm at the root of the aorta. Regarding juvenile cardiopulmonary arrest, there was hypoplasia throughout the aorta in addition to a small aortic root. [1,2,3] In this study, the aortic root was measured in diameter at the inlet along the base of the aortic valve cusps and the outlet along the sinotubular junction (the most distal downstream insertion site of the commissure). The ascending aorta was measured 1 cm above the aortic root. The descending aorta was measured 1 cm above the diaphragm. The abdominal aorta was measured 1 cm below the origin of the renal artery. We also evaluated the right femoral artery diameter, at 2 cm diameter caudal to the inguinal ligament. CT measured the diameters of the outlet and inlet of the aortic root, the ascending aorta, descending aorta, abdominal aorta and right femoral artery. An emergency physician and a radiologist performed measurements, and the average of the results of each measurement was adopted.
The hospital's ethics committee approved the study. The study was performed in accordance with the relevant guidelines and regulations. Statistical analysis was undertaken with RStudio v.1.2.5033, running R v.3.6.1 (https://rstudio.com). Continuous variables were reported as medians and interquartile range (IQR).

Results
Within the study period, there were 1268 cases of total cardiopulmonary arrest (Figure1). Of those, 52 cases were between the ages of 18 and 40. Of the 52 patients, 13 were considered sudden cardiac death or unspeci ed cause of death and were enrolled in this study. Ten of the 13 patients were male, and the median age was 27 (IQR 23-35). In all but one case, 12 patients had CT inspection (92.3%). The arterial diameter was measured in the 12 cases in which CT was performed, and AH was found in eight of the 13 cases (61.5%). Table 1 shows a comparison of AH and non-AH groups. There were ve males (62.5%) in the AH group and four males (100%) in the non-AH group. The age was 28. Moreover, the ascending, descending, and abdominal aorta was also smaller in the AH group. (Table1) The right femoral artery was 6.5 mm (IQR 6.2-7.2) in the AH group and 10.7 mm (IQR 10.1-11.8) in the non-AH group.

Discussion
Among the 13 cases of young adults transferred to our department with a cardiopulmonary arrest status because of cardiogenic or unknown intrinsic diseases, 12 patients underwent CT, and eight (61.5%) had AH. However, AH's clinical signi cance is still not well understood at this time. Most deaths due to AH are thought to be caused by fatal arrhythmias. Additionally, AH may be one of the pathologies of sudden nocturnal death syndrome (SNDS), also thought to be caused by fatal arrhythmias.
SNDS is common in Southeast Asia, for example, the Philippines and Thailand, and is also known as "Pokkuri disease" in Japan. SNDS is a disease that causes sudden death during nighttime sleep in healthy young people, especially males. This is characterized by the fact that there is no suspicious cause of sudden death in terms of circumstances and medical history, and autopsy ndings do not explain the cause of death. Stress, sleep, alcohol consumption, bathing, fever, and fatigue have been highlighted as possible triggers for SNDS. [4] No papers describe the relationship between SNDS and AH. Most reports of SNDS are from East Asia, but the rst reports of AH were from Europe. It is unclear whether AH is found with similar frequency in Asians. However, in this study, AH was found in approximately 60% of young Asian adults who suddenly went into cardiopulmonary arrest. Therefore, AH may be relevant to young Asian adults who suddenly die.
In addition to the aortic root and the entire aorta, the femoral artery was also smaller in the AH group (6.5 vs. 10.7 mm). When a young adult with AH has CPA, the patient must undergo a life-saving veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, the femoral artery is so small that the puncture is di cult. Therefore, it is important to keep in mind that young adults have di culty being cannulated during VA-ECMO introduction.
Since the aortic diameter can be measured by echography, it may help identify young people with AH by incorporating it into school medical examinations. However, its epidemiological signi cance is still unclear, and its use in medical examinations may be di cult. However, especially in those with a family history of younger intrinsic death, such echography to detect AH could be meaningful for diagnosis.
Postmortem changes may alter the arterial diameter. In studies, measurements of the aortic root using autopsy and xed specimens showed that measurements of the heart's semilunar valves did not signi cantly change after death and did not change regardless of the type of xation method. [1] Here, 25% were not AH, and it is unlikely that AH is a postmortem change.
There are several limitations in this study. First, this study was a single-center observational study with a small number of patients. Second, although CT images measured the aortic diameter, most of them were plain CT without contrast agents, thus, having low contrast and are considered inaccurate to some exert or compared with contrast CT. Thus, to validate the accuracy of measurements, a radiologist and an emergency physician's dual assessment were applied. Third, only a small number of cases at our institution were subjected to a pathological autopsy, so we could not examine detailed histological images and pathological ndings. Fourth, since many sudden cardiopulmonary arrests occur in innately healthy young people, there is almost no pre-sudden death data to refer to, which is also a barrier to research. The relationship between AH and sudden cardiopulmonary arrest in young adults, its mechanisms, and epidemiological signi cance are expected to be clari ed in further studies.

Conclusions
In this study, for a decade, 13 young adult cases were of the cardiopulmonary arrest of sudden cardiac death or unknown causes. Of those, eight (61.5%) had AH. Further study should be conducted to reveal the epidemiological signi cance of AH in young adults.