Atrial Septal Defects Mini Review
Abstract
Atrial septal defects (ASD) are holes in the wall separating the right and left sides of the heart's atrium. These atrial holes are formed before birth and some close during infancy. ASDs prevalence is rare and estimated to be in the category of >1/1,000. Its cause is unknown and can be diagnosed through echocardiography. Two genes, NKX2-5 and TBX5, are linked to the disorder. Before diagnosis, it should be distinguished from other heart disorders. ASD may be associated with some disorders, such as Down and Holt-Oram syndromes. It is best treated by surgery to close the hole in the atrial wall and can be managed without surgery through increased cardiac monitoring. The prognosis for those with ASD closure surgery is good. However, outcomes with and without surgery vary based on several factors, such as the location of the atrial hole and the severity of related symptoms.
Keywords: heart septal defect, atria, pulmonary hypertension, cyanosis, right ventricle, atrial arrhythmias
Introduction
The heart is an essential organ that pumps blood throughout the body. Its development is complex and precise. Imperfections in the wall of the upper chamber, the atrium, are rare. Holes in the wall between the right and left side of the upper chamber are called atrial septal defects or ASD. This review will further define these imperfections, differentiate their subtypes, and describe genetic links. In addition, it will provide a discussion of differential diagnoses, prognosis, management, and treatment.
Review
Atrial septal defects (ASD) occur when the space between the heart's atria does not entirely close. The heart is divided into four chambers (Atrial septal defects, 2006). The atria of the heart are located above the ventricles and each is separated into right and left. Therefore, the right atria, left atria, right ventricle, and left ventricle is the four chambers of the heart. In the atria, the septum or fossa ovalis divides the right and left chambers (Nashat et al., 2018). The fossa ovalis develops during the fifth week of gestation (Nashat et al., 2018). ASDs are irregularities or holes in the wall between the atrial chambers. ASDs are present and birth or congenital. They are classified as interatrial communication disorders and "characterized by a communication between the atrial chambers of the heart” (Houyel, 2020). ASD most likely falls in the >1/1,000 category of prevalence. It is the most common congenital heart disorder "with a reported birth prevalence of approximately 1 to 2 per 1000 live births” (Ammash et al.). The four subtypes of ASD and their Orpha numbers are Secundum ASD - 99103, Primum ASD - 99106, Sinus venosus ASD - 99105, and Coronary sinus ASD - 99104 (Orphanet: Atrial septal defect). Figure 1 below from Ammash et al., depicts the different presentations of three of the ASD subtypes.
Figure 1 from Ammash et al.
Clinical Description
The most common subtype of ASD is Osmium Sucundum or Secundum ASD, and it occurs in about 70-75% of all ASD cases (Ammash et al.). In simplistic terms, there is a hole in the middle of the wall between the right and left atria. The symptoms and impact of the sucundum subtype are so mild that the diagnosis may not occur until the patient is about 40. The ostium primum or primum ASD subtype occurs in 15 to 20% of all ASD cases. In this subtype, the hole is closer to the ventricles or lower than a hole in the secundum subtype (Ammash et al.). "Priumum ASD's are nearly always associated with anomalies of the atrioventricular (AV) valves” (Ammash et al.). Given its proximity to the lower chambers of the heart and the frequent impact on the atrioventricular valves, it makes sense that this subtype “has more adverse long-term outcomes than secundum type ASDs" (Nashat et al., 2018).
The least common subtypes of ASD are sinus venous and coronary sinus. Sinus venous ASDs occur in 5-10 percent of all ASD cases and are "often associated with malformations of the vein that leads from the lungs to the heart" (Atrial septal defects, 2006). In simple terms, this hole is located toward the top of the atrium. The unroofed coronary sinus ASD subtype occurs with minor frequency and in less than 1 percent of all ASD cases. It "occurs when part or the entire common wall between the coronary sinus and the left atrium is absent" (Nashat et al., 2018).
Aetiology
Currently, ASD appears to be caused sporadically, and causal mechanisms are unclear. However, there were two autosomal dominant gene variations associated with ASD. In some families, variations in NKX2-5 and TBX5 genes are linked to ASD (Ammash et al.). The NKX2-5 gene is "located on chromosome five (5q34)" (Ellesøe et al., 2016). Ellesøe et al.'s 2016 research has demonstrated an NKX2-5 phenotype which includes a diagnosis of ASD. In addition, their review analysis determined that "ASD was present in 145 (70%) of the mutation carriers” (Ellesøe et al., 2016). In regards to the TBX5 gene, it is the most common cause of Holt-Oram syndrome. Holt-Oram syndrome is characterized by "upper limb defects (deformities of the radius, carpal bones, and/or thumbs) and cardiac septal defects, most commonly a secundum ASD” (Ammash et al.).
Diagnosis
Many individuals with ASD will be asymptomatic until about 40 years of age. However, some early symptoms can include a unique heart murmur, overall thinness and delays in growth, and “increased susceptibility to respiratory infections” (Atrial septal defects, 2006). “Symptoms may include a bluish discoloration of the skin (cyanosis), clubbing of the fingertips, exercise intolerance, and/or an abnormal increase in the number of circulating red blood cells polycythemia”(Atrial septal defects, 2006). In addition, “patients with a systolic murmur at the left sternal border associated with fixed splitting of the second heart sound, unexplained right ventricular volume overload, atrial arrhythmias, or pulmonary hypertension should be referred for evaluation of possible ASD” (Ammash et al.). The primary tests for ASD include electrocardiogram, chest radiograph, echocardiography or ultrasound of the heart, transthoracic echocardiography with agitated saline contrast, transesophageal echocardiography, cardiovascular magnetic residence, cardiac computed tomography, and cardiac catheterization (Ammash et al.). An echocardiography is typically preferred and it will identify small ASDs that can be missed by electrocardiograms (Ammash et al.).
Similar diseases or syndromes should be considered during the diagnostic process. These include heart disorders such as atrioventral septal and ventricular septal defects or imperfections, cor triatriatum, cor triloculare biatriatum, and mitral valve stenosis (Ammash et al.). In addition, ASDs “may occur in association with a variety of other disorders including Down syndrome, Ellis van-Creveld syndrome, Opitz syndrome, Costello syndrome, Chondroectodermal dysplasia, fetal effects of Rubella, Holt-Oram syndrome, Hurler syndrome, and others” (Atrial septal defects, 2006). It would be interesting to see if further studies note a genetic correlation between these associated disorders and NKX2-5 or TBX5 variations.
Prognosis
Many ASDs identified in infancy close on their own by early childhood (Vick et al., 2022). "Children with clinically significant ASDs (ie, secundum ASDs ≥3 mm or defects other than secundum such as sinus venosus or primum or coronary sinus ASDs) should be followed by a pediatric cardiologist every one to two years” (Vick et al., 2022). Surgery to close the irregularity is recommended for children with "right heart enlargement, pulmonary over circulation, and evidence of substantial left-to-right shunting” ((Vick et al., 2022). In adults, the prognosis is good for individuals who have surgery to close the atrial hole. The outcomes depend upon the size of the septal hole, the presence and size of heart chamber enlargement, and the presence of other symptoms or related conditions such as pulmonary hypertension. In a large nationwide 2018 study, Nyboe et al. demonstrated that without surgery, "almost half the patients died from cardiac disease". However, "the patients without closure were older at the time of diagnosis and had more comorbidity” (Nyboe et al., 2018).
Treatment and Management
If the septum irregularity does not close independently, surgery will reduce risks for other health complications. The other health complications include atrial arrhythmias, pulmonary hypertension, and maternal cardiac risk (Connolly et al., 2022). ASD closure is indicated for the majority of cases. ASD closure is contraindicated for individuals with Eisenmenger's syndrome. Additional pre-surgical consultation with adult congenital heart disease and pulmonary hypertension experts should occur for individuals who do not meet all three of the following criteria; pulmonary artery systolic pressure less than 50% of the systemic systolic blood pressure, pulmonary vascular resistance less than one-third of systemic vascular resistance, and no cyanosis at rest or during exercise (Connolly et al., 2022). Pre-surgical consultation is also recommended for individuals with platypnea-orthodeoxia caused by ASD and evidence of paradoxical embolism (Connolly et al., 2022).
Additional and routine monitoring is suggested for individuals without ASD closure. In particular, "patients with small ASDs (less than 10 mm) with no evidence of RV enlargement or pulmonary hypertension (PH) should receive periodic routine follow-up to monitor for development of symptoms (eg, arrhythmias or paradoxical embolism), RV enlargement, or PH" (Connolly et al., 2022). In addition, activities that involve "fluctuations in ambient air pressure," should be avoided by those without ASD closure (Connolly et al., 2022). "ASD has been associated with increased risks of decompression illness and paradoxical emboli among individuals who SCUBA dive. SCUBA diving is generally contraindicated in patients with an unrepaired ASD" (Connolly et al., 2022). Also, exposure to high-altitudes, such as hiking Kilimanjaro, would put the individual at risk. "Patients with ASDs are at risk for increased right-to-left shunting and oxygen desaturation at high altitudes" (Connolly et al., 2022). Finally, additional consultation and monitoring by a cardiologist is suggested for pregnant women with ASD "and a history of supraventricular arrhythmias or RV failure" (Connolly et al., 2022).
Conclusion
Atrial septal defects (ASD) are irregularities in the atrial wall of the heart. While the majority of these holes close on their own, surgery may be indicated to close these atrial gaps. The prognosis for ASD closure surgery is good and reduces risk due to pregnancy, exposure to high altitudes, SCUBA diving, pulmonary hypertension, and heart arrhythmias. The gap's position on the atrial wall categorizes it into four subtypes. The most common subtype, secundum ASD, can exist without exhibiting symptoms for decades and may have little impact on the individual. The more impactful subtypes occur in less than one to 20% of all ASD cases. Although ASD is caused sporadically, some familial forms are linked to autosomal dominant variations of the NKX2–5 and TBX5 genes. ASD is best diagnosed via echocardiography. Symptoms include but are not limited to a unique heart murmur, cyanosis, pulmonary hypertension, atrial arrhythmias, and exercise intolerance.
List of Abbreviations Used
ASD or Atrial Septal Defects
AV or atrioventricular
PH or pulmonary hypertension
RV or right ventricle
SCUBA or Self-Contained Underwater Breather Apparatus
References
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Nyboe, C., Karunanithi, Z., Nielsen-Kudsk, J. E., & Hjortdal, V. E. (2018). Long-term mortality in patients with atrial septal defect: a nationwide cohort-study. European heart journal, 39(12), 993–998. https://doi.org/10.1093/eurheartj/ehx687
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