Marfan syndrome (MFS) is a hereditary disorder caused by a genetic mutation that weakens the body’s connective tissue, the material providing structure and support to organs and tissues. This compromise affects the integrity of connective tissue throughout the body. While the syndrome affects many systems, the cardiovascular system is the area of most concern because complications here are the primary cause of illness and reduced lifespan. The fundamental weakness in the blood vessel walls and heart valves leads to mechanical problems that require lifelong monitoring and management.
The Fibrillin Defect and Aortic Disease
The root cause of Marfan syndrome’s cardiovascular problems is a mutation in the FBN1 gene, which provides instructions for making the protein Fibrillin-1. Fibrillin-1 is a structural component of microfibrils, which are essential to the elastic fibers found in the walls of the aorta and other blood vessels. When this protein is defective, the aorta’s wall loses its necessary strength and elasticity, a condition referred to as aortopathy.
This structural weakness is most pronounced at the aortic root, the section of the aorta closest to the heart where it connects to the aortic valve. This area is constantly subjected to high pressure and mechanical stress from the forceful pumping of the heart. Over time, the weak aortic wall stretches and enlarges, leading to progressive Aortic Root Dilation. Aortic dilation is the most common and serious cardiovascular feature of MFS, affecting up to 90% of patients.
The most severe acute complication of this dilation is Aortic Dissection. This occurs when a tear forms in the innermost layer of the aortic wall, allowing blood to rush through and split the middle layer, separating it from the outer layer. This is a life-threatening medical emergency and the main cause of sudden death in people with Marfan syndrome. Prophylactic surgical intervention is therefore aimed at preventing this catastrophic event before it can occur.
Impact on Cardiac Valves and Other Structures
The compromised connective tissue also significantly affects the heart’s valves, which rely on this tissue for their structure and ability to open and close correctly. Mitral Valve Prolapse (MVP) is a highly prevalent issue in MFS, occurring in about 60% of people with the condition. MVP is characterized by the leaflets of the mitral valve—which separates the left upper and lower heart chambers—bulging or prolapsing backward into the upper chamber during a heartbeat.
When the leaflets prolapse, they may not close tightly, which allows blood to leak backward into the upper chamber, a condition known as Mitral Regurgitation. If this leak is severe, the heart has to work much harder to pump enough blood, which can eventually lead to heart failure or cause the upper chamber to become dilated. The presence of MVP that requires surgery is associated with a more severe overall disease phenotype.
The aortic valve, located at the connection between the heart and the aorta, can also be affected by the widening aortic root. As the root dilates, it can stretch the aortic valve leaflets, preventing them from closing completely. This results in Aortic Regurgitation, where blood leaks back into the heart’s pumping chamber. While less common than mitral involvement, the tricuspid valve on the right side of the heart can also be affected, with Tricuspid Valve Prolapse often indicating a more severe overall disease presentation.
Monitoring and Management of Heart Complications
Managing the cardiovascular aspects of Marfan syndrome requires regular, close medical supervision to track the size and health of the aorta and heart valves. Diagnostic tools used to monitor the aorta’s diameter and the valves’ function include transthoracic echocardiography, which is a non-invasive ultrasound of the heart. For a more complete view of the entire aorta, including segments beyond the aortic root, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans are also used periodically.
The goal of medical therapy is to slow the rate of aortic dilation and reduce the strain on the aortic wall. Medications such as Beta-blockers are commonly prescribed to slow the heart rate and decrease the force of the heartbeat, thereby reducing hemodynamic stress on the aorta. Angiotensin Receptor Blockers (ARBs), such as Losartan, are another class of medication often used, sometimes in combination with beta-blockers, as they are thought to offer additional benefits by interfering with the disease’s underlying cellular pathways.
Prophylactic surgery is performed to replace the dilated section of the aorta before it reaches a size where the risk of dissection becomes unacceptably high. Current guidelines generally recommend considering elective aortic root replacement surgery when the aortic diameter reaches or exceeds 5.0 centimeters in adults. However, surgery may be recommended at a smaller diameter, such as 4.5 centimeters, if the patient has other high-risk factors, including a rapid rate of aortic growth or a family history of dissection. Women planning a pregnancy are also often advised to undergo surgery if their aortic root diameter is 4.5 centimeters or greater, due to the increased stress on the aorta during gestation.