Decision-making in aortic root surgery in Marfan syndrome: bleeding, thromboembolism and risk of reintervention after valve-sparing or mechanical aortic root replacement†

OBJECTIVES Valve-sparing root replacement (VSRR) is thought to reduce the rate of thromboembolic and bleeding events compared with aortic root replacement using a mechanical aortic root replacement (MRR) with a composite graft by avoiding oral anticoagulation. But as VSRR carries a certain risk for subsequent reinterventions, decision-making in the individual patient can be challenging. METHODS Of 100 Marfan syndrome (MFS) patients who underwent 169 aortic surgeries and were followed at our institution since 1995, 59 consecutive patients without a history of dissection or prior aortic surgery underwent elective VSRR or MRR and were retrospectively analysed. RESULTS VSRR was performed in 29 (David n = 24, Yacoub n = 5) and MRR in 30 patients. The mean age was 33 ± 15 years. The mean follow-up after VSRR was 6.5 ± 4 years (180 patient-years) compared with 8.8 ± 9 years (274 patient-years) after MRR. Reoperation rates after root remodelling (Yacoub) were significantly higher than after the reimplantation (David) procedure (60 vs 4.2%, P = 0.01). The need for reinterventions after the reimplantation procedure (0.8% per patient-year) was not significantly higher than after MRR (P = 0.44) but follow-up after VSRR was significantly shorter (P = 0.03). There was neither significant morbidity nor mortality associated with root reoperations. There were no neurological events after VSRR compared with four stroke/intracranial bleeding events in the MRR group (log-rank, P = 0.11), translating into an event rate of 1.46% per patient-year following MRR. CONCLUSION The calculated annual failure rate after VSRR using the reimplantation technique was lower than the annual risk for thromboembolic or bleeding events. Since the perioperative risk of reinterventions following VSRR is low, patients might benefit from VSRR even if redo surgery may become necessary during follow-u

Outcome of aortic surgery in patients with Loeys-Dietz syndrome primarily treated as having Marfan syndrome†

OBJECTIVES Loeys-Dietz syndrome (LDS) is characterized by acute aortic dissection (AAD) at aortic diameters below thresholds for intervention in patients with Marfan syndrome (MFS). The aim was to evaluate the outcome of LDS patients primarily treated as having MFS. METHODS We analysed 68 consecutive patients who underwent surgery between 1995 and 2007 under the assumption of having MFS before retrospectively being screened for LDS when genetic testing became available. These patients were followed up until 2013, and underwent a total of 115 aortic surgeries. RESULTS Genetic testing was performed in 76% of the patients. Sixty per cent of these patients were positive for FBN1 mutations associated with MFS, 20% had no FBN1 mutation and 17% harboured TGFBR1/2 mutations associated with LDS. Mean follow-up was 12.7 ± 7 years. All-cause 30-day, 6-month and 1-year mortality rates were 2.9, 4.4 and 7.3%, respectively. Interestingly, initial presentation with AAD did not differ between LDS and MFS (33 vs 37%, P = 0.48) nor did long-term mortality compared with MFS patients (11 vs 16%, P = 1.0) or within MFS subgroups (FBN1 positive 13%, P = 1.0; FBN1 negative 10%, P = 1.0; not tested 25%, P = 0.62). There was no difference in the need for secondary total arch replacement between LDS and MFS patients (11 vs 14%, P = 1.0), nor within MFS subgroups (FBN1 positive 16%, P = 1.0; FBN1 negative 10%, P = 1.0; not tested 13%, P = 1.0). Total aortic replacement became necessary in 22% of LDS compared with 12% of MFS patients (P = 0.6) and did not differ significantly between MFS subgroups. CONCLUSIONS Although early surgical intervention in LDS is warranted to avoid AAD, the current data suggest that once the diseased segment is repaired, there seems to be no additional burden in terms of mortality or reoperation rate compared with that in MFS patients, with or without confirmed FBN1 mutatio

Should aortic arch replacement be performed during initial surgery for aortic root aneurysm in patients with Marfan syndrome?†

OBJECTIVES The aim of this study was to investigate whether total arch replacement (TAR) during initial surgery for root aneurysm should be routinely performed in patients with Marfan syndrome (MFS). METHODS Retrospective analysis of 94 consecutive MFS patients fulfilling Ghent criteria who underwent 148 aortic surgeries and were followed at this institution during the past 16 years. RESULTS The mean follow-up interval was 8.8 ± 7 years. Initial presentation was acute aortic dissection (AAD) in 35% of patients (76% Type A and 24% Type B) and aneurismal disease in 65%. TAR was performed in 8% of patients during initial surgery for AAD (otherwise a hemi-arch replacement was performed) and 1.6% in elective root repair. Secondary TAR had to be performed in only 3% of patients without, but in 33% following AAD (33% Type A and 33% Type B; P = 0.0001). Thirty-day, 6-month, 1-year and overall mortalities were 3.2, 5.3, 6.4 and 11.7%, respectively. Operative and 30-day mortalities in secondary aortic arch replacement were zero. Secondary TAR after AAD did not increase the need for the replacement of the entire thoracoabdominal aorta during follow-up compared with patients without secondary TAR (37 vs 40%, P = 1.0). CONCLUSIONS MFS patients undergoing elective root repair have small risk of reinterventions on the aortic arch, and primary prophylactic replacement does not seem to be justified. In patients with AAD, the need for reinterventions is precipitated by the dissection itself and not by limiting the procedure to the hemi-arch replacement in the emergency setting. Limiting surgery to the aortic root, ascending aorta and proximal aortic arch is associated with low mortality in MFS patients presenting with AA

What makes the difference between the natural course of a remaining type B dissection after type A repair and a primary type B aortic dissection?†

OBJECTIVES To analyse the outcome and need for intervention [surgery or thoracic endovascular aortic repair (TEVAR)] in patients after surgery for remaining type B dissection after type A repair and primary type B aortic dissection. METHODS Within a 10-year period, 247 patients with remaining type B after type A, and 112 patients with primary type B aortic dissection were analysed. We assessed the clinical outcome as well as the need for intervention (surgery or TEVAR) within the aortic arch and the thoracoabdominal aorta as well as risk factors. RESULTS The median follow-up was 23 months (interquartile range 5-52). There was a significant difference with regard to the status of the primary entry tear between patients after surgical repair of an acute type A aortic dissection and primary acute type B aortic dissection (patent vs. non-patent entry 35 vs. 83%, P<0.001). The overall need for any kind of intervention (surgery or TEVAR) was 19%. Multivariate Cox regression analysis revealed a patent primary entry tear in patients after surgery for acute type A aortic dissection as an independent predictor for intervention (surgery or TEVAR) during follow-up [odds ratio (OR) 6.4; confidence interval (CI) 1.39-29.81, P=0.017]. Multivariate Cox regression analysis did not reveal a patent primary entry tear in patients after acute type B aortic dissection as an independent predictor for intervention (surgery or TEVAR) during follow-up (OR 0.67; CI 0.27-1.69, P=0.671). Finally, the thrombosis status of the false lumen was not an independent predictor for intervention (surgery or TEVAR) either in patients after surgery for acute type A aortic dissection (OR 3.46; CI 0.79-15.16, P=0.100) or in patients after acute type B aortic dissection (OR 0.77; CI 0.31-1.93, P=0.580). CONCLUSIONS A remaining type B dissection after type A repair and a primary type B aortic dissection represent two distinct pathophysiological entities with regard to late outcome. The need for any kind of intervention in the thoracoabdominal aorta is significantly higher in primary type B aortic dissections. A remaining patent primary entry tear independently predicts the need for intervention (surgery or TEVAR) in patients after surgery for acute type A aortic dissection and, thereby, remains the main target of initial therapy. The thrombosis status of the false lumen seems to be of secondary importanc

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.00