Patent foramen ovale pathophysiology

During the 4th week of gestation, formation of the atrial septum begins. Formation of the septum primum and septum secundum leads to the development of a foramen ovale which allows blood to flow from the right atrium to the left atrium in the fetus. Fusion of both septa’s occurs after birth with increased left atrial pressure. The foramen ovale remains patent in some people due to failure of fusion of the septum primum and septum secundum. This permits blood flow from the right atrium to the left atrium during periods of increased right atrial pressure. Some conditions associated with patent foramen ovale include cryptogenic stroke, migraine with aura, and decompression sickness in divers.

• Atrial septation begins at about the 4th week of gestation. A crescent-shaped septum primum grows from the primordial atrial roof towards the endocardial cushion and partially divides the common atrium into right and left halves.^[1][2]
• Formation of the endocardial cushions occurs on the ventral and dorsal walls of the atrioventricular canal. Before the septum primum reaches the endocardial cushion, programmed cell death occurs in the more cranial part giving rise to perforations that become a large window called the ostium secundum/foramen secundum.
• Around day 33, a crescent-shaped septum secundum forms on the right side of the septum primum. It grows gradually and overlaps part of the ostium secundum/foramen secundum forming an oval-shaped, incomplete septal partition that becomes the foramen ovale. The foramen ovale permits blood to pass from the right atrium to the left atrium.
• A flap-like valve is formed by the remaining septum primum over the foramen ovale. Fusion of both septa’s occur after birth.

• In fetal circulation, oxygenated blood from the placenta flows through the umbilical vein to the inferior vena cava and makes its way into the right atrium. Due to greater right atrial pressure compared to left atrial pressure in utero, blood flows from the right atrium to the left through the foramen ovale. Blood from the left atrium flows into the left ventricle, into the aorta and to the systemic circulation. The deoxygenated blood from the systemic circulation travels back to the placenta through the umbilical arteries for oxygenation by the mother.^[2]
• At birth, oxygen fills the alveolus resulting in a drop in right heart pressure and pulmonary vascular resistance. The amount of blood entering the left atrium from the lungs increases leading to increased left atrial pressure. These mechanisms cause closure of the foramen ovale. In most individuals, the foramen ovale closes by age two.

• Soon after birth, as an infant takes its first breath, the negative intrathoracic pressure closes the foramen ovale. It may remain open in a number of people due to failure of fusion of the septum primum and septum secundum making the closure incomplete. This patent foramen ovale permits interatrial flow of blood from the right atrium to the left atrium during periods when the right atrial pressure exceeds that of the left atrium, for example, coughing, sneezing or straining^[3][4]
• It is undetected in a majority of people and may be seen during cardiac investigation.^[3]
• Patent foramen ovale allows intermittent right-to-left shunting of blood across the atrial septum. In the presence of a venous thrombus, this shunt may permit embolic material to bypass the pulmonary circulation and enter the systemic arterial circulation, resulting in paradoxical embolism and ischemic stroke.Anatomical characteristics that may increase shunt flow and embolic risk include large shunt size, atrial septal aneurysm, long PFO tunnel, and the presence of a Eustachian valve, an embryologic remnant in the right atrium.^[5]

• F2 (prothrombin) and Apolipoprotein-C3 genes may be associated with patent foramen ovale.^[6]

Conditions associated with patent foramen ovale include:^[7][8][9]

• Cryptogenic stroke
• Migraine headache
• Atrial septal aneurysm
• Chiari network
• Obstructive sleep apnea
• Decompression sickness

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