Personalized external aortic root support (PEARS): A narrative review

Central MessagePEARS is an operation to prevent dilatation and to maintain aortic valve function in Marfan and other aortic root aneurysms.PerspectiveAs the result of patient and family awareness and access to echocardiography and radiologic imaging, individuals with genetically triggered aortopathy with root aneurysm present earlier. For them, PEARS complements root replacement surgery.See Commentary on page XXX. PEARS is an operation to prevent dilatation and to maintain aortic valve function in Marfan and other aortic root aneurysms. As the result of patient and family awareness and access to echocardiography and radiologic imaging, individuals with genetically triggered aortopathy with root aneurysm present earlier. For them, PEARS complements root replacement surgery. See Commentary on page XXX. We review the development and present status of personalized external aortic root support (PEARS) in a chronological narrative. PEARS was first proposed to the UK Marfan Association in 2000 by Tal Golesworthy, a developmental engineer with Marfan syndrome. His aortic diameter had increased from 44 mm to 49 mm over 12 years. He questioned what had been told by his cardiologist—that he should have his ascending aorta and aortic valve replaced, followed by lifelong anticoagulation. He had heard Tom Treasure's annual lecture to families with Marfan syndrome, which included timing of surgery with reference to correspondence with Vincent Gott in the New England Journal of Medicine.1Treasure T. Chow T. Gallivan S. Replacement of the aortic root in Marfan's syndrome.N Engl J Med. 1999; 341: 1473-1474Google Scholar In the postlecture Q&A, Golesworthy challenged the need for extirpative surgery. He envisaged the application of modern science to revisit the then 30-year-old idea of externally supporting an aortic aneurysm.2Robicsek F. Daugherty H.K. Mullen D.C. External grafting of aortic aneurysms.J Thorac Cardiovasc Surg. 1971; 61: 131-134Google Scholar He foresaw computer modeling, with data from digital images being used to generate a physical replica of the individual's aorta by 3-dimensional printing. On that former, a personalized well-fitting sleeve would be fashioned to prevent further expansion. During the following few years, Golesworthy and Treasure investigated the feasibility of the idea. Golesworthy came to the operating theaters to see what was entailed in total root replacement. Together, they went to Robert Anderson to take a focused look at the morphology of the aortic root. Golesworthy collaborated with Michael Lampérth and Warren Thornton of Imperial College London to develop computer-aided design modeling for rapid prototyping, now known as 3-dimensional printing. Because the intention was to support rather than to replace the aorta, a porous knitted fabric was chosen to avoid graft migration and vascular erosion,3Plonek T. A metaanalysis and systematic review of wrapping of the ascending aorta.J Card Surg. 2014; 29: 809-815Google Scholar the known consequences of wrapping with stiff low-porosity material. It was decided to use the same polymer, polyethylene terephthalate (Dacron), because of its proven biocompatibility. With John Pepper, we discussed the surgical method of implantation, repeatedly and in detail. Pepper negotiated with the Royal Brompton Hospital a trial of the new procedure in 20 patients, conducted in accordance with the requirements of the Research Ethics Committee. All patients were informed that this was innovative surgery and discussed risks and benefits with the operating surgeon. The first operation, on Golesworthy, appeared as a research letter in The Lancet.4Golesworthy T. Lamperth M. Mohiaddin R. et al.A jacket for the Marfan's aorta.Lancet. 2004; 364: 1582Google Scholar Surgeons embarking on PEARS are proctored by experienced operators and must study the instructions for use. In addition to the published method of implantation,5Pepper J. Petrou M. Rega F. et al.Implantation of an individually computer-designed and manufactured external support for the Marfan aortic root.Multimed Man Cardiothorac Surg. 2013; 2013mmt004https://doi.org/10.1093/mmcts/mmt004Google Scholar 2 teams in the PEARS diaspora have contributed “How to do it” papers, which provide further expert insights.6Kenny L.A. Austin C. Golesworthy T. et al.Personalized external aortic root support (PEARS) for aortic root aneurysm.Op Tech Thorac Cardiovasc Surg. 2021; 26: 290-305Google Scholar,7Nemec P. Kolarik M. Fila P. Personalized external aortic root support—how to implant it.Acta Chir Belg. 2022; 122: 70-73Google Scholar The ExoVasc device and the steps in the operation have remained unchanged, which we attribute to the time spent in basic research collaboration and careful planning. Bentall's total root replacement8Bentall H. De Bono A. A technique for complete replacement of the ascending aorta.Thorax. 1968; 23: 338-339Google Scholar and David’s valve sparing operation9David T.E. The aortic valve-sparing operation.J Thorac Cardiovasc Surg. 2011; 141: 613-615Google Scholar were conceived at the operating table and then progressively evolved in clinical practice. The aorta is mobilized from the aortoventricular junction to beyond the brachiocephalic artery. Dissection is straightforward in the noncoronary sinus. It is more difficult in the right coronary sinus because of the proximity of the muscular free-wall of the right ventricular. The challenge in the left coronary sinus is the close proximity of right ventricular outflow tract and the pulmonary artery. Details are shown in elegant and informative drawings in Kenny’s description.6Kenny L.A. Austin C. Golesworthy T. et al.Personalized external aortic root support (PEARS) for aortic root aneurysm.Op Tech Thorac Cardiovasc Surg. 2021; 26: 290-305Google Scholar Dissection is made easier by avoiding cardiopulmonary bypass and anticoagulation—as has been done in 79% of cases to date—and by lowering the blood pressure and heart rate, and exercising great patience. It is also facilitated by the greater length of aortic root proximal to the coronary origins, which is a feature of Marfan morphology. Once the ExoVasc sleeve is in place, laminar flow in the coronary arteries is confirmed by transesophageal echocardiography. In 2 instances, the surgeon did not properly dissect the aortic root and the root aneurysm continued to enlarge. At repeat operations, it was discovered that the critical area of the aortic root, proximal to the coronaries, had never been dissected or supported. These breaches of the operative protocol—effectively sham operations—are mentioned to emphasize the importance of strict adherence to the method.10Austin C. Thompson P. Fittipaldi M. et al.The consequences of incomplete covering of the critical part of the aortic root in Personalized External Aortic Root Support.Eur J Cardiothorac Surg. 2021; 59: 1095Google Scholar In a study designed and implemented in the Clinical Operational Research Unit at University College London, magnetic resonance imaging scans of the aortic root, before and at 6, 12, 24, and/or 36 months after the first 10 PEARS operations, were cropped to remove identifiers and dates. They were placed in random sequence with duplicate images of 37 unoperated patients with Marfan syndrome. Three commissure-to-sinus measurements were made “blind” by an independent vascular radiologist. No supported root had further enlarged, and 8 of 10 were markedly reduced, and remained so, with preservation of the sinus morphology.11Pepper J. Golesworthy T. Utley M. et al.Manufacturing and placing a bespoke support for the Marfan aortic root: description of the method and technical results and status at one year for the first ten patients.Interact Cardiovasc Thorac Surg. 2010; 10: 360-365Google Scholar In studies in the Department of Engineering at Imperial College London 2015-2016, the characteristics of the neoaorta created by mesh incorporation were explored with finite element modeling. Both circumferential and axial wall stress were seen to be reduced by up to 52% after PEARS implantation.12Singh S.D. Xu X.Y. Pepper J.R. et al.Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.J Biomech. 2016; 49: 2076-2084Google Scholar Most type A dissections originate from a transverse tear close to the sinotubular junction.13Beller C.J. Labrosse M.R. Thubrikar M.J. et al.Role of aortic root motion in the pathogenesis of aortic dissection.Circulation. 2004; 109: 763-769Google Scholar PEARS eliminates this process by reducing the axial displacement. The first 20 patients who received PEARS were matched for age and root size with patients having conventional root replacement at other hospitals where PEARS was not available. Only 1 of 20 patients who received PEARS (the first) had cardiopulmonary bypass; none had myocardial ischemia. They had shorter operation times, markedly less blood loss, and only one had a blood transfusion. None needed platelets or clotting factors.14Treasure T. Crowe S. Chan K.M. et al.A method for early evaluation of a recently introduced technology by deriving a comparative group from existing clinical data: a case study in external support of the Marfan aortic root.BMJ Open. 2012; 2e000725Google Scholar Surgeons and scientists in Leuven, Belgium, performed recovery experiments (2013-2017) in sheep15Van Hoof L. Verbrugghe P. Verbeken E. et al.Support of the aortic wall: a histological study in sheep comparing a macroporous mesh with low-porosity vascular graft of the same polyethylene terephthalate material.Interact Cardiovasc Thorac Surg. 2017; 25: 89-95Google Scholar,16Vastmans J. Fehervary H. Verbrugghe P. et al.Biomechanical evaluation of a personalized external aortic root support applied in the Ross procedure.J Mech Behav Biomed Mater. 2018; 78: 164-174Google Scholar and found that the PEARS mesh was densely and consistently incorporated in the vascular adventitia.15Van Hoof L. Verbrugghe P. Verbeken E. et al.Support of the aortic wall: a histological study in sheep comparing a macroporous mesh with low-porosity vascular graft of the same polyethylene terephthalate material.Interact Cardiovasc Thorac Surg. 2017; 25: 89-95Google Scholar,17Verbrugghe P. Verbeken E. Pepper J. et al.External aortic root support: a histological and mechanical study in sheep.Interact Cardiovasc Thorac Surg. 2013; 17: 334-339Google Scholar There has been only one opportunity to confirm incorporation in humans. The 16th PEARS patient operated on in 2008 at the Royal Brompton Hospital died in his sleep of a presumed arrhythmia in 2013.18Pepper J. Goddard M. Mohiaddin R. et al.Histology of a Marfan aorta 4.5 years after personalized external aortic root support.Eur J Cardiothorac Surg. 2015; 48: 502-505Google Scholar The aortic valve was normal and competent. On histologic examination, the mesh was incorporated into the aortic adventitia. Characteristic medial degeneration was seen distal to the support but within the implant, there was normal histology.18Pepper J. Goddard M. Mohiaddin R. et al.Histology of a Marfan aorta 4.5 years after personalized external aortic root support.Eur J Cardiothorac Surg. 2015; 48: 502-505Google Scholar The pathologic interpretation was that absence of stress in the media of the supported part of the aorta allowed recovery of collagen formation. The tenth PEARS recipient was referred because her Marfan-related aneurysm had expanded during pregnancy. She wanted a PEARS operation to protect her during a subsequent planned pregnancy. She described her “patient's journey” in the BMJ.19Allen C. Pepper J. External aortic support for people with Marfan's syndrome.BMJ. 2010; 340c1692Google Scholar We know of 13 would-be mothers who have had PEARS without evidence of further aortic enlargement and 14 subsequent successful pregnancies. One had her operation (off-pump) during her second trimester. All are well and the number of pregnancies may be an underestimate because pregnancy and childbirth are not routine items for enquiry after aneurysm surgery. Early in the experience, 2 patients had a PEARS implant and mitral valve repair during the same operation.20Benedetto U. Jin X.Y. Hill E. et al.An option for concomitant management of moderate Marfan root aneurysm at the time of mitral valve repair: a role for personalized external aortic root support.Ann Thorac Surg. 2016; 102: e499-e501Google Scholar A total of 43 patients have had both procedures. In some cases, mitral regurgitation is the driving indication. PEARS has also been used to support the pulmonary autograft in the Ross operation. The first 50 patients to have a Ross PEARS operation by Conal Austin were presented at The American Association for Thoracic Surgery and are published.21Redondo A. Austin C. Our 7-year experience supporting the Ross autograft with the novel technique of personalized external aortic root support.J Thorac Cardiovasc Surg Tech. 2024; 24: 121-127Google Scholar The thousandth patient landmark was reached in Spring 2024, but because of an exponential increase in case numbers, only 218 are 5 or more years after operation, so analysis of long-term outcomes would be premature. However, in the 20 years of clinical experience to date no patient in whom the ExoVasc PEARS device has been correctly implanted has demonstrated subsequent dilatation or dissection of the supported ascending aorta. The follow-up study of the first 200 patients who had PEARS for aortic root aneurysm22Van Hoof L. Rega F. Golesworthy T. et al.Personalised external aortic root support for elective treatment of aortic root dilation in 200 patients.Heart. 2021; 107: 1790-1795Google Scholar and a matched-pairs comparison with valve-sparing root replacement are summarized in Table 1.23Van Hoof L. Lamberigts M. Noe D. et al.Matched comparison between external aortic root support and valve-sparing root replacement.Heart. 2023; 109: 832-838Google ScholarTable 1Data on the first 200 primary PEARS operations22Van Hoof L. Rega F. Golesworthy T. et al.Personalised external aortic root support for elective treatment of aortic root dilation in 200 patients.Heart. 2021; 107: 1790-1795Google Scholar and a matched comparison of PEARS and VSSR23Van Hoof L. Lamberigts M. Noe D. et al.Matched comparison between external aortic root support and valve-sparing root replacement.Heart. 2023; 109: 832-838Google ScholarVariablePEARS 200PEARS 80VSRR 80P valueN (% or IQR)N (% or IQR)N (% or IQR)Male138 (69%)57 (71.3%)57 (71.3%)1.00Age33 (23-45)31.7 (21.5-42.5)32 (26.25-38).63Root diameter47 (44-49)48 (46-50)48 (46-49)1.00Marfan147 (74%)77 (96.3%)64 (80.0%)Reoperation for bleeding0 (0%)6 (7.5).03Stroke2 (1%)1 (1.3%)1 (1.3%)1.00Death1 (0.5)0 (0%)0 (0%)1.00Length of stay, d6 (5-7)7 (6-9)<.001AR grade 0-1/preoperative80 (100%)80 (100%)AR grade 0/4 postoperative69 (83.6%)62 (77.5%)NSAR grade last F-U<.010/464 (85.4%)41 (57.8%)1/410 (13.3%)25 (35.2%)2/41 (1.3%)2 (2.8%)≥3/40 (0%)3 (4.3%)P values are for the 2 right-hand columns. PEARS, Personalized external aortic root support; VSSR, valve-sparing root replacement; IQR, interquartile range; AR, aortic regurgitation; NS, not significant; F-U, follow-up. Open table in a new tab P values are for the 2 right-hand columns. PEARS, Personalized external aortic root support; VSSR, valve-sparing root replacement; IQR, interquartile range; AR, aortic regurgitation; NS, not significant; F-U, follow-up. Increased awareness of the possibility of root aneurysms in families affected by inherited connective tissue disease has resulted in people presenting early in the natural history of their disease. The PEARS operation is designed precisely for these patients. Outcomes in the matched comparison are similar, but there is a significant difference in progression of aortic valve regurgitation.