Hidenori Shibamura

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 (Naff) 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, Naff, 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.

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.

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.

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.

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

BackgroundChronic 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.MethodsHLA-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.ResultsWe 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).ConclusionThis 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.

Stent-grafting to descending thoracic aorta during coronary artery bypass grafting

We report on 2 patients who underwent successful concomitant operation of coronary artery bypass grafting and stent grafting to descending thoracic aortic aneurysms. The device was inserted through a small linear incision on the anterior wall of the aortic arch. Intraoperative stent grafting to descending thoracic aortic aneurysms is an alternative therapeutic option for patients who require concomitant coronary artery bypass grafting and descending aortic replacement.

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

Abstract:  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.