Case Study in Loeys-Dietz Syndrome: Multiple Problems Promptly Addressed in a Single Operation

Presentation

A 12-year-old boy with Loeys-Dietz syndrome (LDS) was referred for surgical evaluation after MRI revealed a large left subclavian aneurysm originating near the aortic arch that had not been seen on his monitoring scan the year before.

He had been diagnosed at another hospital with LDS when he was 2 years old, at which time valve-sparing aortic root replacement was performed, leaving him with mild aortic regurgitation. He had been followed since his diagnosis by Kenneth Zahka, MD, a Cleveland Clinic pediatric cardiologist specializing in genetic forms of heart disease. At the time of his current presentation, he was being managed on an angiotensin II receptor blocker and a beta-blocker as well as annual echocardiography and head-to-pelvis MRI surveillance.

The patient’s LDS also manifested with severe pectus excavatum and scoliosis. He had his first major operation to address the latter in the preceding year.

CT scanning with 3D reconstruction was performed for more-detailed evaluation (see images below). Close examination revealed that the left subclavian aneurysm was particularly close to the left vertebral artery, potentially complicating repair. In addition, his stable ascending aneurysm was noted beyond the prior root replacement.

“Frequent and thorough monitoring is essential in patients with Loeys-Dietz syndrome, as they can quickly develop aneurysms anywhere,” says Dr. Zahka. “When an aneurysm is detected, prompt action is needed because progression tends to be rapid.”

All-in-one surgery

A surgical team was quickly assembled, including pediatric cardiac surgeon Alistair Phillips, MD, thoracic surgeon Daniel Raymond, MD, and adult cardio-aortic surgeon Eric Roselli, MD, because of the complexity of features not often encountered in pediatric practice.

During a single seven-hour operation (including about 45 minutes with hypothermic selective brain perfusion), the team performed the following (see image below):

• Aortic valve repair
• Ascending and total arch replacement and modified elephant trunk surgeries
• Excision and bypass of the left subclavian aneurysm
• Transposition of the left vertebral artery to the left carotid
• Pectus excavatum repair

Recovery was unremarkable, with a few days in the intensive care unit and another week in the general hospital ward. At two-month follow-up, the boy was doing well. The medical management and surveillance he had prior to surgery were resumed. His scoliosis will continue to be addressed with future surgeries as needed as to accommodate his growth.

Discussion: An LDS primer

LDS has been recognized as an entity separate from Marfan’s syndrome for only a decade and a half. While musculoskeletal abnormalities are more variable in LDS compared with Marfan syndrome, patients with LDS typically do not have cataracts or displaced lenses, and LDS should come to mind when a young patient is found to have a large aortic root. A bifid uvula is another classic finding, although it is not always present. Other distinctive clues to LDS include clubfoot, craniosynostosis and premature osteoarthritis (SMAD3 subtype).

Specific genetic mutations (TGFBR1, TGFBR2, SMAD3, TGFB2 and TGFB3) are inherited in an autosomal dominant pattern, with TGFBR1 and TGFBR2 identifying the most aggressive subtypes of LDS, characterized by aortic dissection and rupture at an earlier age and smaller aortic diameter. Genetic testing of the patient’s family members for LDS is indicated. (The case patient’s genetic mutation arose de novo.)

Early surgery leads to better outcomes

Although LDS is associated with a malignant prognosis, the chance for a normal life span is dramatically improved by early recognition, close monitoring and aggressive intervention. Cleveland Clinic has the largest published experience of patients with LDS, consisting of 53 patients, 33 of whom underwent aortic surgery (J Thorac Cardiovasc Surg. 2019;157:439-450.e5). Early prophylactic surgery was key to avoiding catastrophic outcomes and improving long-term survival in this series. These patients benefit from the multidisciplinary expertise of Cleveland Clinic’s Aorta Center and its Cardiovascular Marfan and Connective Tissue Clinic.

“Thinking about the future was how we decided to correct many problems at once for this patient,” says Dr. Roselli. “We didn’t want him to face multiple surgeries — which he would have certainly required over the next several years — if we could avoid it.”

The cardiac surgeons involved in the case, Drs. Roselli and Phillips, formulated the aggressive plan along with Dr. Zahka and the pediatric heart team and believed the boy was large enough for an adult graft to set him up successfully. Simultaneously addressing his pectus excavatum with Dr. Raymond’s expertise enabled the surgeons to have adequate exposure to the aortic valve, the ascending aorta and the aortic arch, where the new rapidly expanding aneurysm originated.

“Future aortic aneurysm surgeries have been made simpler — likely amenable to stent placement — because of the elephant trunk graft now in place,” Dr. Roselli says. He notes that endovascular repair of a localized segment of aorta is reasonable in patients with connective tissue disorders when provided with the reliability of a surgical graft for the proximal landing zone, as a Cleveland Clinic group has shown (Ann Thorac Surg. 2016;101:906-912).

Ingredients for success: Experience, collaboration

LDS presents a cluster of problems uncommonly seen in pediatric surgery, including anatomical variations, a large aortic root and multiple aggressive aneurysms. The characteristic extremely fragile tissues (particularly in the branch vessels) make addressing these issues especially challenging. Patients should be managed under the guidance of a large institution that has experience with such cases, where they can also undergo surgery when indicated.

The highly complex surgery performed in this case was made possible by exemplary collaboration among a team of pediatric and adult specialty cardiothoracic surgeons in concert with the primary cardiologist. In addition, experienced cardiology imaging specialists, cardiothoracic anesthesiologists, pediatric intensivists, perfusionists, and cardiovascular nurses were instrumental to this unique surgery’s success.

“Patients with LDS are particularly prone to aortic dissection, and safe prophylactic surgery is imperative for long-term survival, as our team demonstrated,” observes Cleveland Clinic Heart & Vascular Institute Chair Lars Svensson, MD, PhD. “In our review of 53 LDS patients [J Thorac Cardiovasc Surg. 2019;157:439-450.e5], there were no deaths after reimplantation surgery, and the long-term results were excellent. However, if aortic dissection occurred before surgery, the results were not as good.”

“There’s no doubt this young patient will still have medical challenges,” concludes Dr. Zahka. “He will need to continue his close monitoring throughout life, but this operation has gone a long way toward a more optimistic prognosis.”