Impact of Alpha Gal Syndrome on Early Bioprosthetic Heart Valve Degradation
Abstract
Alpha-gal is a carbohydrate that is expressed in all animals except for humans. It is found in red meat, dairy, and other animal-derived products including surgical implants and drugs. The human immune system uniformly tolerates this foreign, non-human, carbohydrate, although some patients develop Alpha-gal Syndrome (AGS), or an allergy to it. This allergy is caused by a bite from the Lone Star tick. Symptoms are delayed and exist on a continuum, ranging from vague abdominal pain to life-threatening anaphylaxis following exposure to alpha-gal. AGS continues to be a chronic, underreported and often unrecognized allergic condition, effecting an estimated 20% of people in regions endemic to the Lone Star tick, like the Southeastern United States. Alpha-gal is present on tissue valves used in heart surgery. Tissue valves are artificial heart valves made from pig or cow tissue. They are popular because they can be placed through a minimally invasive approach and do not require patients to be on blood thinners after surgery. Historically though, younger patients were precluded from receiving tissue valves because younger patients have stronger immune responses, which cause more damage when the foreign valve is initially implanted, shortening the expected lifetime of the valve from 15 years to 5. Our team (Drs. Joseph Turek, study Principal Investigator and Scott Commins, study Consultant/Contractor) have shown that patients with AGS, or an allergy to alpha-gal, have a stronger immune response to tissue valves than their peers. Alpha-gal is removed from animal-derived surgical implants by the immune system during the first year after implantation. We believe the stronger immune response associated with AGS, a tick-borne disease, contributes to increased valvular damage within the first year, predisposing patients to early valve failure following tissue-based heart valve replacement. In this study, we will (1) measure how an alpha-gal allergy (AGS) effects valve function in patients undergoing tissue-based valve replacement, (2) use a novel animal model to demonstrate the isolate effect of AGS on valve function following tissue-based valve replacement , and (3) attempt to prevent AGS related valvular damage in the animal model using a commercially available allergy medication. In Aim 1, we will be collecting blood from patients undergoing aortic valve replacement at Duke University, once preoperatively and once at patients’ 1-year follow-up. Patients testing positive for an alpha-gal allergy at either time will be considered to have AGS. Valve function based on routine ultrasound and the need for redo valve replacement will be compared between these two study groups (those with and without AGS). In Aim 2, we will use special pigs that lack alpha-gal (like humans), give them Lone Star tick toxin (simulating a tick bite), and create an AGS model. By implanting aortic valves from other pigs with and without alpha-gal into these AGS pigs, we can isolate and measure the true impact AGS has on valve structure and function. In Aim 3, we will utilize the same approach from Aim 2, but selectively treat pigs with Omalizumab, a Food and Drug Administration-approved allergy medication that has been shown to treat refractory AGS patients with severe symptoms. Heart disease is the leading cause of death in the United States, with annual costs over $350 billion. Valvular heart disease accounts for $23 billion of this total cost, affecting 11% of Americans. Tissue-based heart valves represent the majority of these repairs and will continue to outpace mechanical valve replacement. Early valve damage following tissue-based heart valve replacement affects approximately 20% of patients and is associated with premature valve failure and redo valve replacement. The number of adults 65 and older is expected to double over the next 30 years, making AGS-related valve damage an unmet public health concern worth studying, particul
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310881
Entities
People
- Joseph W. Turek
Organizations
- Duke University
- United States Army