Long-term results of the frozen elephant trunk technique for the extensive arteriosclerotic aneurysm.

OBJECTIVES: The objective of this report is to elucidate the feasibility of the frozen elephant trunk technique as a one-stage operation for extensive arteriosclerotic aneurysms and to investigate the long-term durability and efficacy of this procedure from our 11 years of experience. METHODS: The subjects were 58 consecutive patients who electively received the frozen elephant trunk technique for arteriosclerotic aneurysms involving the aortic arch and the descending aorta between September 1997 and September 2008. Concomitant procedures included 15 coronary artery bypass grafts, 2 aortic valve replacements, 1 aortic root replacement, and 3 maze procedures. The stent graft was delivered to the seventh thoracic vertebra level (Th7) in 22, Th8 in 26, Th9 in 8, and Th10 in 2 patients. Cerebrospinal fluid drainage was administered preoperatively in 10 (17.2%) patients. RESULTS: Operative mortality within 30 days was 0 of 58. There was 1 in-hospital death. Perioperative morbidity included strokes and spinal cord injury in 2 (3.4%) patients each. During the mean follow-up period of 54.2 +/- 36.9 months, there were 9 (15.5%) late deaths, and 7 (12.1%) patients required additional intervention. The 8-year survival was 65.5%, the overall 8-year aortic event free survival was 72.8%, and the 8-year event free survival on the site of the stent graft was 94.8%. A follow-up computed tomographic image was available for 86.2% (50/58) of patients who survived longer than 6 months. The size of the aneurysm increased in 1 (2.0%) patient, was not changed in 6 (12.0%) patients, shrank in 34 (68.0%) patients, and was obliterated in 9 (18.0%) patients. CONCLUSIONS: The frozen elephant trunk for extensive aortic aneurysms had long-term durability and efficacy and might become the alternative treatment for extended aortic replacement.

Operative strategy for acute type a aortic dissection: ascending aortic or hemiarch versus total arch replacement with frozen elephant trunk.

BACKGROUND: This report compares long-term results with total arch replacement with frozen elephant trunk (FET) to ascending aortic or hemiarch replacement (AHR) for acute type A aortic dissection. METHODS: The subjects were 120 consecutive patients, including 65 who received FET and 55 who had AHR for acute type A aortic dissection from 1997 to 2008. The late results after surgery were retrospectively compared between the FET and ARH groups. RESULTS: Three patients in the FET group died, and 2 patients in the AHR group died. In long-term follow-up (mean, 67 months), the survival rate after 5 years was 95.3% for the FET group and 69.0% for the AHR group (p = 0.03). The event rate for the thoracic aorta after 5 years showed a significant difference between the FET and AHR groups (95.7% versus 73.0%, p = 0.01). A false lumen at the proximal descending aorta was patent in 16 patients (29%) in the AHR group, but it was thrombosed in all in the FET group. CONCLUSIONS: In patients with acute type A aortic dissection, it is possible to perform extensive primary repair using the FET technique with relative safety. FET may reduce the necessity for further operations to manage a residual false lumen.

Surgical strategies for organ malperfusions in acute type B aortic dissection.

This study is retrospectively to evaluate strategies for organ malperfusion on the view point of two mechanisms (true lumen collapse in the aorta=Ao type, or branch dissection=Br type) in acute type B aortic dissection. There were 16 of Ao type and 4 of Br type in 20 patients with organ malperfusion. In Ao type, we performed entry closure in 12 patients, surgical bypass grafting in two to superior mesenteric artery (SMA) in one and femoral artery in two, and surgical fenestration in two. In Br type, we performed interventional non-covered stenting to the orifice of visceral arteries in two patients, surgical bypass to SMA with ileum resection in one, and surgical bypass to SAM and renal arteries in one. Five patients in 16 of Ao type died within 30 days that had two multiple organ failure after entry closure, one aortic injury during endovascular stent graft repair, two more multiple organ failure after femoral bypass, however, all four patients in Br type were rescued. Central aortic operation to true lumen collapse with entry closure for Ao type ischemia and organ reperfusion with extra-anatomical bypass or non-covered stent to ischemic arteries for Br type ischemia should be performed before catastrophic status.

Total arch replacement with an open stent graft for acute type A aortic dissection: fate of the false lumen.

OBJECTIVE: To describe the fate of the false lumen remaining in the descending thoracic aorta after extensive primary repair of the thoracic aorta by the modified elephant trunk technique with a stent graft for acute type A aortic dissection, particularly the changes of the false lumen on enhanced CT scanning. METHODS: The subjects were 65 consecutive patients who received arch replacement with an open stent graft for type A acute aortic dissection. CT scanning was performed at 1, 3, 12, 36, and 60 months postoperatively to detect thrombus formation, absorption of thrombus, and obliteration of the false lumen after its exclusion by the stent graft. The aorta was measured at four levels, which were the distal border of the stent graft, the middle and distal parts of the descending thoracic aorta, and the origin of the superior mesenteric artery. RESULTS: Obliteration was recognized in all patients at the distal border of the stent graft and absorption of thrombus was seen in 90% at the middle of the descending thoracic aorta within 1 year after surgery. However, the false lumen remained patent at the superior mesenteric artery (SMA) level in 50% of the patients. CONCLUSIONS: In patients with acute type A aortic dissection, it is possible to perform extensive primary repair of the thoracic aorta with relative safety by stent grafting, and this method may reduce the necessity for further operations to manage a residual false lumen.

HLA-DQA is associated with abdominal aortic aneurysms in the Belgian population.

Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA-DQA1 locus among Belgian males, and found a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study.

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Midterm results of extensive primary repair of the thoracic aorta by means of total arch replacement with open stent graft placement for an acute type A aortic dissection.

OBJECTIVES: We sought to describe the midterm results of extensive primary repair of the thoracic aorta by means of the modified elephant trunk technique with a stent graft for acute type A aortic dissection, particularly the changes of the false lumen shown by enhanced computed tomographic scanning. METHODS: The subjects were 35 consecutive patients who received arch replacement with open stent grafting for type A acute aortic dissection between December 1997 and April 2002. The mean follow-up period was 55 months (range, 30-83 months). Computed tomographic scanning was performed at 1, 3, 12, and 36 months postoperatively to detect thrombosis and obliteration of the false lumen after its exclusion by the stent graft. The diameter of the aorta was measured at 3 levels: the distal edge of the stent graft, the diaphragm, and the origin of the superior mesenteric artery. RESULTS: Two patients died in the initial operation, but no patients required additional surgical treatment of the thoracic aorta. The mean diameter of the stent grafts was 26.2 mm, and the mean length was 8.9 cm. Thrombus formation in the false lumen was recognized at the distal edge of the graft in all patients, at the diaphragmatic level in 26 patients, and at the superior mesenteric artery level in 15 patients. Obliteration of the false lumen was recognized at the distal edge of the graft in all patients, at the diaphragmatic level in 20 patients, and at the superior mesenteric artery level in 15 patients. The aorta distal to the stent graft showed minimal changes. CONCLUSIONS: In patients with acute type A aortic dissections, it is possible to perform extensive primary repair of the thoracic aorta with relative safety by using a synthetic graft with a self-expanding stent, and this method might reduce the necessity of further operations not only for the distal descending aorta but also for the thoracoabdominal aorta.

Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. RESULTS: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.

Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. METHODS AND RESULTS: We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N(aff)) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (P=0.00014) with sex, N(aff), and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 (P=0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. CONCLUSIONS: Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

Familial abdominal aortic aneurysms: collection of 233 multiplex families.

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. SUBJECTS AND METHODS: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags). RESULTS: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. CONCLUSION: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors.