Yutaka Okita

Eight novel mutations of the FBN1 gene found in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, is caused by mutations in the gene encoding fibrillin 1 (FBN1). The clinical spectrum and severity of MFS disorder varies greatly both between and within families. Since there have been only a few reports on the relationship between FBN1 genotypes and clinical phenotypes in Japanese patients, the FBN1 gene was analyzed in 27 Japanese patients diagnosed with MFS. The nucleotide sequence of the 65 exons of the FBN1 gene was analyzed by PCR and direct sequencing. We have identified six polymorphisms and nine mutations including: four missense mutations (C1652Y, Q2054P, D2127Y, C2221R) in six patients, three nonsense mutations (R215X, S813X, R2220X) in three patients, and two frameshift mutations (2567insT, 7790insT) in three patients. Six of these nine mutations were in the calcium‐binding epidermal growth factor‐like domains all causative mutations detected except for C2221R were novel. It has been reported that the severe phenotypes of infantile MFS correlate with mutations in the mid region of FBN1, however, mutations were not detected in this region in the population analyzed in this study. Our results suggest that the location of the mutation is not the sole determinant of phenotypic severity; rather there is some difference in the genetic basis of MFS between Japanese and Caucasian populations.

Surgery for Extensive Thoracic Aortic Aneurysm

Methods: Forty-three consecutive patients underwent the repair of ETAA from 1999 to 2007. There were 17 patients in one stage group (63.2 ± 11.3y), while 21 patients in staged repair group (60.3 ± 16.6y). All patients in one stage group, underwent the ascending aorta and aortic arch replacement in combined with various extensions of descending aortic replacement (proximal 5, middle 8, total descending 1, or thoracoabdominal aorta 3). In staged repair group, second-stage repair were performed (Surgery: 14, Stent graft 7) after the first-stage graft replacement (total arch replacement (TAR) 7, TAR + aortic root replacement (ARR) 7, TAR + Coronary artery bypass grafting ± ARR 7).

Surgical treatment of mycotic aortic aneurysms and management of aortic graft infections.

Mycotic aortic aneurysms are uncommon, but when a fulminant infectious process occurs it frequently results in rupture and death if not properly treated. Infection of a vascular graft is one of the most serious postoperative complications that faces a cardiovascular surgeon. We evaluated the results of surgical treatment for mycotic aortic aneurysms and aortic graft infections. Between 1980 and 1999 a total of 16 patients with mycotic aortic aneurysms (13 in the thoracic aorta, 3 in the abdominal aorta) underwent surgery. The surgical procedures were in situ reconstruction in eight patients, extraanatomic bypass in seven, and resection in one. Seven patients died during the hospital stay. Between 1977 and September 1999 we treated 39 patients with aortic graft infection (34 in the thoracic aorta, 5 in the abdominal aorta). The incidence of aortic graft infection was 1.7% (39/2350) among the patients who underwent aortic aneurysm operations. Graft infections were controlled in nine patients. Disinfection followed by tissue flap coverage of the graft proved to be effective for controlling the serious graft infection. Surgical techniques for treating these conditions should be modified to improve the surgical outcome in these patients.

Strategies for Preventing Spinal Cord Ischemia During Descending or Thoracoabdominal Aortic Aneurysm Surgery: Preoperative Visualization of the Adamkiewicz Artery and Intraoperative Motor-Evoked Potentials

We report here our recent strategies for preventing spinal cord ischemia during surgery for descending or thoracoabdominal aortic aneurysms. A total of 25 patients underwent replacement of the thoracoabdominal or descending aorta. The age of the patients ranged from 29 to 83 years (59.4 ± 12.8 years), and the male/female ratio was 18:7. Sixteen patients had nondissecting aneurysms and nine had aortic dissection. Twenty-one patients underwent open surgery, and four patients underwent endovascular stent-graft repair. Preoperative magnetic resonance angiography (MRA) was used to visualize the Adamkiewicz artery, and there were intraoperative recordings of myogenic motor-evoked potentials (MEP) using a transcranial stimulator. Femorofemoral bypass with a heparin-coated circuit under mild hypothermia (30°-32°C) was used. The Adamkiewicz arteries were demonstrated in 18 patients (72%); they originated from the left intercostal or lumbar arteries in 13 (72%) patients, from the right intercostal or lumban arteries in 5 (28%), and from the T8 branch in 2, T9 in 7, T10 in 2, T11 in 2, T12 in 1, and L1 in 2. The MEPs were recorded in 22 patients (88%). In 10 patients there was a transient decrease of the potentials, although the amplitude resumed after reconstructing the intercostal arteries or after rewarm-ing. Two patients died of graft infections and bowel necrosis (7.1%) after open surgery; there was no spinal cord injury among the survivors. We concluded that preoperative detection of the Adamkiewicz artery by MRA and intraoperative MEP monitoring were useful for reducing the incidence of spinal cord injury during surgery for aneurysms of the thoracoabdominal or descending aorta.

Valve-Sparing Operation Versus Bentall Operation: Comparison at Medium-Term Follow-Up

The valve-sparing operation has been proposed for aortic regurgitation (AR) in the setting of aortic root dilatation. This method has several advantages over the Bentall operation. Since 1994 a total of 37 patients have undergone either reimplantation of the aortic valve (12 patients) or remodeling of the aortic root (25 patients) in our institution (group R). During the same period 33 patients have had the Bentall operation (group B) as elective surgery. The mean follow-up periods were 323 days (17–1457 days) in group A and 712 days (15–1620 days) in group B. In group R seven patients had Marfan syndrome, five had aortic dissection, and three had aortitis syndrome. In group B nine patients had Marfan syndrome, two had aortic dissection, and eight had aortitis syndrome. There were no differences in preoperative New York Heart Association class or age at operation between the two groups. There was one hospital death in each group and one late death in group B. Two patients in group R required reoperation but none in group B. Actuarial survivals at 4 years were 96.7% in group R and 94.0% in group B. The event-free rates at 4 years were 94.6% in group R and 93.9% in group B. The reoperation-free rates at 4 years were 94.6% in group R and 100% in group B. There was no statistical difference between the two groups for all rates. The valve-sparing operation maintains valve competence during the early postoperative course in our experience, but follow-up data showed deterioration of the valve competence after reimplantation or remodeling, particularly when aortic regurgitation, even mild, was seen after operation. The medium-term survival and cardiac event rates for the valve-sparing operation showed no statistical difference from those of the Bentall operation, although the long-term results of valve competence after the valve-sparing operation are still not known. The aortic root replacement technique should be selected in each clinical setting.

Surgical Approaches to Nondissecting Atherosclerotic Aneurysms of the Distal Aortic Arch or Proximal Descending Aorta Using Deep Hypothermic Circulatory Arrest with Retrograde Cerebral Perfusion: Midsternotomy and Left Lateral Thoracotomy

Surgical results in patients with nondissecting atherosclerotic aneurysms of the distal aortic arch or proximal descending aorta were investigated in relation to two approaches to the aneurysm: midstemotomy or posterolateral left thoracotomy. From May 1993 to April 1998 a total of 118 patients with nondissecting aneurysms of the distal arch underwent surgery. Patients were divided into two groups: 73 patients with midstemotomy (group A) and 45 with posterolateral left thoracotomy (group B). The mean ages were 70.4 ± 5.9 years in group A and 68.5 ± 9.0 years in group B. Indications for midstemotomy were severe atherosclerosis of the proximal arch in 30 patients, aneurysms involved the proximal arch in 15, ruptured aneurysm in 8, chronic obstructive pulmonary disease in 7, coronary artery bypass grafting of the right coronary artery in 5, redo after left thoracotomy in 5, severe aortic regurgitation in 3, carotid surgery in 2, and the presence of an aberrant right subclavian artery in 2. Indications for left thoracotomy were coexistent aneurysms of the descending aorta in 26 patients, normal proximal arch in 16, redo after midstemotomy in 2, and ruptured aneurysm in 1. A technique using deep hypothermic circulatory arrest with retrograde cerebral perfusion was used in all patients. In group A, 65 patients had total arch replacement, 3 distal arch replacement, 1 distal arch and descending aorta replacement, and 5 patch repair. In group B, 2 patients had total arch replacement, 16 replacement of the distal arch, 23 distal arch and descending aorta replacement, and 4 patch repair. There were eight hospital deaths in group A compared with three in group B. One patient in group A had a stroke, as did 5 in group B (P = 0.019). Transient brain dysfunction was found in 23 patients of group A and in 14 of group B. There was no difference in operating time or bypass time, but circulatory arrest and cardiac ischemic times were longer in group A. Postoperative wake-up times, mechanical ventilation times, intensive care unit stays, and postoperative hospital stays were similar. Although surgical approaches for nondissecting aneurysms of the distal aortic arch or proximal descending aorta should be chosen depending on the individual, total arch replacement through a midsternotomy is recommended whenever feasible because of the lower incidence of postoperative stroke compared with left thoracotomy.