Research Highlights:
- Using ultrasound guidance, researchers successfully repaired a potentially deadly vascular malformation, called vein of Galen malformation, deep in the brain of a fetus before birth. The malformation, which has massively high blood flow, often leads to heart failure, severe brain injury or possibly death soon after birth.
- The first in-utero embolization repair was successfully performed on a fetus at 34 weeks and 2 days gestational age. Fetal ultrasound showed an immediate drop in abnormal blood flow through the brain malformation, and fetal echocardiography showed significant improvement in heart function the day after the procedure.
- Since birth, the infant has required no medication to treat heart failure and no postnatal surgery to treat the malformation. Repeated echocardiograms after birth displayed marked improvement in cardiac output, and brain MRIs showed no brain injury and a normal neurological exam.
Newswise — DALLAS, May 4, 2023 —A recent study published in Stroke, the leading peer-reviewed journal of the American Stroke Association, a branch of the American Heart Association, reports that scientists have accomplished a prosperous prenatal operation to address a possibly fatal developmental ailment. The treatment was directed towards a malignant vascular abnormality, known as the vein of Galen malformation, in the brain of the fetus, making it the first of its kind.
The vein of Galen malformation (VOGM) is a prenatal abnormality that occurs rarely. In this condition, arteries that carry high-flow and high-pressure blood from the heart to the brain directly link to one of the principal collecting veins located deep at the base of the brain, rather than to the capillaries responsible for slowing blood flow and supplying oxygen to adjacent brain tissue. Following birth, modifications in the infant's vascular physiology exacerbate the high flow in the malformation, causing severe effects on the heart and brain and exerting significant pressure on the newborn's heart and lungs. This may result in potentially fatal conditions such as pulmonary hypertension, heart failure, among others. Prenatal ultrasound typically first identifies VOGM, and MRI provides a definitive diagnosis in the late second or third trimester of pregnancy.
As part of an ongoing clinical trial conducted under the supervision of the U.S. Food and Drug Administration, the researchers carried out in-utero embolization on a fetus with VOGM at 34 weeks and 2 days gestational age. This marked the first patient to receive this treatment at Boston Children's Hospital and Brigham and Women's Hospital.
Darren B. Orbach, M.D., Ph.D., co-director of the Cerebrovascular Surgery & Interventions Center at Boston Children's Hospital and an associate professor of radiology at Harvard Medical School, who led the study, reported that in their ongoing clinical trial, they are employing ultrasound-guided transuterine embolization to address the vein of Galen malformation before birth. In the first case, they were delighted to see that the usual aggressive decline following birth did not occur. The infant has made remarkable progress in six weeks, with no medication, normal eating, weight gain, and being back home. Additionally, there have been no indications of any adverse effects on the brain.
As a result of premature rupture of membranes during the in-utero embolization, the infant was delivered by vaginal birth induction two days after the procedure. Echocardiography after delivery revealed a gradual normalization of cardiac output. Following the in-utero treatment, the newborn did not require any cardiovascular support or surgery, and was under observation in the NICU for a few weeks due to prematurity before being released. Throughout this period, the infant underwent normal neurological examinations and exhibited no signs of strokes, fluid accumulation, or hemorrhage on brain MRI.
Orbach stated that while this is only the first treated patient, it is crucial to continue the trial to evaluate the safety and effectiveness in other patients. This approach has the potential to revolutionize the management of vein of Galen malformation, as it repairs the malformation before birth, preventing heart failure before it occurs instead of attempting to reverse it after birth. As a result, there may be a significant reduction in the risk of long-term brain damage, disability, or death among infants with this condition.
VOGM is the most prevalent congenital vascular brain malformation, with an estimated occurrence rate of one in every 60,000 births. Embolization, a catheter-based treatment to block off the direct artery-to-vein connections in the malformation and impede the excess blood flow to the brain and heart, is the current standard of care for VOGM after birth. However, embolization itself poses a significant risk and may not always reverse heart failure. Moreover, severe brain damage may have already developed, resulting in lifelong cognitive impairments and life-threatening conditions for the infant, or even death.
Gary M. Satou, M.D., FAHA, the director of pediatric echocardiography at UCLA Mattel Children's Hospital and co-director of the UCLA Fetal Cardiology Program, who was not involved with the study, commented that "The fetal intervention team at Boston Children’s Hospital and Brigham and Women’s Hospital have successfully devised another in utero procedure that may be very impactful in a specific group of patients diagnosed with vein of Galen malformation." Satou, a pediatric cardiologist, is a former chair of the American Heart Association’s Congenital Cardiac Defects committee of Young Hearts Council and a clinical professor in the department of pediatrics at the David Geffen School of Medicine at UCLA.
Dr. Satou emphasizes the importance of conducting more cases and following up on outcomes to establish a clear pattern of improvement in both neurologic and cardiovascular outcomes. He believes that the ongoing clinical trial is crucial for gathering adequate data and achieving successful outcomes.
Colin P. Derdeyn, M.D., a neurointerventional radiologist at University of Iowa Health Care who performs VOGM embolizations on neonates and was not part of the study, mentioned that the procedure had its restrictions.
"The major advancement in this case is the ability to intervene before the physiological events of birth, which can lead to life-threatening heart failure. However, caution must be exercised as one successful case is insufficient to conclude that the benefits outweigh the risks of the procedure. Future procedures may encounter safety issues, and this vein-based approach may not consistently prevent heart failure. It is important to note that the described procedure aims to reduce the flow through the malformation rather than cure it," warned Derdeyn, a neurointerventional radiologist at University of Iowa Health Care who performs VOGM embolizations on neonates, and who was not involved with the study. Derdeyn is also the Krabbenhoft Professor of Radiology, Chair, and Department Executive Officer of the Department of Radiology at the University of Iowa Health Care Carver College of Medicine and a past chair of the American Heart Association’s Stroke Council.
The co-authors of the study include Louise E. Wilkins-Haug, M.D.; Carol B. Benson, M.D.; Wayne Tworetzky, M.B. Ch.B.; Shivani D. Rangwala, M.D.; Stephanie H. Guseh, M.D.; Nicole K. Gately, R.N.; Jeffrey N. Stout, Ph.D.; Arielle Mizrahi-Arnaud, M.D.; and Alfred P. See, M.D. Any conflicts of interest or financial disclosures for the authors are reported in the manuscript.
The study received funding from the Sage Schermerhorn Chair for Image-Guided Therapy (DBO) in the Radiology Department at Boston Children's Hospital.
This statement emphasizes that the American Heart Association's scientific journals publish studies with statements and conclusions solely from the authors, which do not necessarily reflect the Association's policy or position. The accuracy and reliability of the studies are not guaranteed by the Association. The Association receives funding from individuals, foundations, and corporations, including pharmaceutical and device manufacturers and other companies, but has strict policies to prevent these relationships from influencing the science content. The Association's financial information is available for review, including revenue from pharmaceutical and biotech companies, device manufacturers, and health insurance providers.
RSS