Mutations in a TGF-ß ligand, TGFB3, cause syndromic aortic aneurysms and dissections.

BACKGROUND: Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-ß signaling. OBJECTIVES: This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. METHODS: We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. RESULTS: Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-ß signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-ß signaling in association with up-regulation of the expression of TGF-ß ligands. CONCLUSIONS: Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk.

Long-term outcomes after immediate aortic repair for acute type A aortic dissection complicated by coma.

OBJECTIVES: The management of acute type A aortic dissection complicated by coma remains controversial. We previously reported an excellent rate of recovery of consciousness provided aortic repair was performed within 5 hours of the onset of symptoms. This study evaluates the early and long-term outcomes using this approach. METHODS: Between August 2003 and July 2013, of the 241 patients with acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma Scale was less than 11 on arrival. Surgery was performed in 186 patients, including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent successful aortic repair immediately (immediate group). Their mean age was 71.0 ± 11.1 years, Glasgow Coma Scale was 6.5 ± 2.4, and prevalence of carotid dissection was 79%. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative induced hypothermia was performed. Neurologic evaluations were performed using the Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin Scale. RESULTS: In the immediate group, the time from the onset of symptoms to arrival in the operating theater was 222 ± 86 minutes. Hospital mortality was 12.5%. Full recovery of consciousness was achieved in 79% of patients in up to 30 days. Postoperative Glasgow Coma Scale and National Institutes of Health Stroke Scale improved significantly when compared with the preoperative score (P < .05), and postoperative activities of daily living independence (modified Rankin Scale <3) was achieved in 50% of patients. The mean follow-up period was 56.5 months, and the cumulative survival was 48.2% after 10 years. Cox proportional hazards regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007) was the only significant predictor of postoperative survival over a 5-year period. CONCLUSIONS: The early and long-term outcomes as a result of immediate aortic repair for acute type A aortic dissection complicated by coma were satisfactory.

Impact of controlled pericardial drainage on critical cardiac tamponade with acute type A aortic dissection.

BACKGROUND: Cardiac tamponade is associated with fatal outcomes for patients with acute type A aortic dissection, and the presence of cardiac tamponade should prompt urgent aortic repair. However, treatment of the patient with critical cardiac tamponade who cannot survive until surgery remains unclear. We analyzed our experience of controlled pericardial drainage (CPD) managing critical cardiac tamponade. METHODS AND RESULTS: Between September 2003 and May 2011, 175 patients with acute type A aortic dissection were treated surgically, including 43 (24.6%) who presented with cardiac tamponade on arrival. Eighteen patients, who did not respond to intravenous volume resuscitation, underwent CPD in the emergency department. An 8F pigtail drainage catheter was inserted percutaneously, and drainage volume was controlled by means of several cycles of intermittent drainage to maintain blood pressure at ≈90 mm Hg. After CPD, all of the patients were transferred to the operating room, and immediate aortic repair was performed. Systolic blood pressure before CPD was 64.3 ± 8.2 mm Hg and elevated significantly in all of the cases after CPD. Systolic blood pressure after CPD was 94.8 ± 10.5 mm Hg, and increase in systolic pressure was 30.5 ± 11.7 mm Hg. Total volume of aspirated pericardial effusion was 40.1 ± 30.6 mL, and 10 patients required only ≤30-mL aspiration volume. All of the patients underwent aortic repair successfully. In-hospital mortality was 16.7%; however, there was no complications or mortality related to CPD. CONCLUSIONS: Preoperative pericardial drainage with control of volume is a safe and effective procedure for acute type A aortic dissection complicated by critical cardiac tamponade. In our patient population, timely controlled pericardial drainage is warranted.

Neurological outcomes after immediate aortic repair for acute type A aortic dissection complicated by coma.

BACKGROUND: Management of acute type A aortic dissection (AADA) complicated by coma remains controversial. We analyzed our experience in managing AADA complicated by coma to determine the relationship of duration of preoperative coma to postoperative neurological recovery. METHODS AND RESULTS: Between September 2003 and October 2010, 181 patients with AADA were treated, including 27 presenting with coma (Glasgow Coma Scale <11) on arrival. Twenty-one patients were repaired immediately (immediate group); time from onset of symptoms to operating room was <5 hours. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative therapeutic hypothermia with magnesium treatment was performed. Six patients initially were managed medically, and 3 of them were followed by eventual repair because time from onset was >5 hours (delayed group). The preoperative National Institutes of Health Stroke Scale score was 31.4 ± 6.6 in the immediate group and 28.3 ± 9.5 in the delayed group. Hospital mortality was 14% in the immediate group and 67% in the delayed group. Full recovery of consciousness was achieved in 86% of patients in the immediate group and in 17% in the delayed group. In immediate group, the postoperative National Institutes of Health Stroke Scale score significantly improved to 6.4 ± 8.4, cumulative survival rate was 71.8% in 3 years, and independence in daily activities was achieved in 52% (11/21). CONCLUSIONS: Aortic repair, if performed immediately from the onset of symptoms, showed satisfactory recovery of consciousness and neurological function in patients with AADA complicated by coma. In this patient population, immediate aortic repair is warranted.

Recurrent severe mitral regurgitation due to left ventricular apical wall motion abnormality caused by coronary vasospastic angina: a case report.

A 76-year-old man developed congestive heart failure due to severe mitral regurgitation after episodes of vasospastic angina. Echocardiography demonstrated left ventricular apical akinesis with ballooning and deformity of the anterior mitral leaflet becoming concave toward the left atrium. The acetylcholine provocation test induced diffuse coronary vasospasm in the distal segments of both right and left coronary arteries and reproduced severe mitral regurgitation. Follow-up echocardiography demonstrated decreased mitral regurgitation with ameliorated apical wall motion. Coronary vasospasm remained refractory to antivasospastic medications and severe mitral regurgitation relapsed 1 month after discharge. Mitral valve annuloplasty with a Carpentier-Edwards physio ring was performed, and no recurrence of mitral regurgitation was observed despite some episodes of vasospastic angina. We speculate that vasospastic angina and the resultant apical wall motion abnormality caused tethering of the mitral subvalvular apparatus, leading to inappropriate mitral coaptation and severe regurgitation.

Retrievable Günther Tulip filter complicated by sepsis and retroperitoneal hemorrhage: successful management by filter retrieval.

We encountered complications of septic shock and retroperitoneal hemorrhage which occurred after implantation of a retrievable Günther Tulip filter. A 79-year-old woman was diagnosed as right femoral vein thrombosis, and a retrievable Günther Tulip filter was deployed prior to a total knee replacement surgery. However, the patient developed septicemia due to Citrobacter freundii, followed by thrombocytopenia and retroperitoneal hemorrhage. A large hematoma was formed along the lateral side of the filter struts. We considered that the filter should be removed to control retroperitoneal hemorrhage and prevent secondary infection of the hematoma. Removal of the retrievable filter was effective in managing these complications.

Transbrachial arterial insertion of aortic occlusion balloon catheter in patients with shock from ruptured abdominal aortic aneurysm.

OBJECTIVE: Of 125 surgical patients with abdominal aortic aneurysm (AAA) treated from 1999, 11 patients with deep shock from ruptured AAAs who underwent aortic occlusion balloon catheter (AOBC) insertion before laparotomy were studied. METHODS: With the patients under local anesthesia, the brachial artery was exposed and the balloon catheter was inserted into the thoracic aorta. The balloon was inflated halfway and pulled back gently to the orifice of the left subclavian artery, and was advanced with the aid of blood flow down to the abdominal aorta. After full inflation of the balloon, the catheter was pulled until the balloon was fixed at the proximal shoulder of the AAA. RESULTS: AOBC insertion was completed within 16.1 +/- 5.1 minutes. Systolic blood pressure at presentation was 84.1 +/- 31.7 mm Hg, deteriorated to 60.9 +/- 15.4 mm Hg on arrival in the operating room, and increased significantly (P <.0001) to 123.4 +/- 25.3 mm Hg after AOBC insertion. The balloon burst in three patients. Embolic complications were observed in two patients. There were three deaths, two associated with the balloon bursting. In nine patients whose shock was successfully controlled by AOBC, operative mortality was 11%. CONCLUSION: Transbrachial arterial insertion of an AOBC may be useful to ameliorate hemorrhagic shock in patients with ruptured AAAs.

Rib-cross thoracotomy for replacement of the thoracoabdominal or total descending aorta.

We describe the use of rib-cross thoracotomy and costal coaptation pins made with bioabsorbable poly-L-lactide for rib approximation. This thoracotomy provided an excellent intraoperative exposure of the entire descending aorta and thoracoabdominal aorta in patients with extended thoracoabdominal aortic aneurysm without increase in postoperative morbidity.

Reconstruction of right ventricular outflow tract with stentless xenografts in Ross procedure.

To investigate whether the use of a stentless porcine aortic xenograft can be an alternative for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure, 9 patients underwent the Ross procedure and RVOT reconstruction with a stentless xenograft since January 2000. After the aortic valve was replaced with a pulmonary autograft, a stentless xenograft with a xeno- pericardial roll was implanted in the RVOT. One patient required subsequent aortic valve replacement because of severe regurgitation of the pulmonary autograft. All patients recovered well from the operation. The right ventricle-pulmonary arterial pressure gradient was 18 +/- 7 mm Hg at discharge and was not significantly increased during the 2-year follow-up period. Although 1 patient died of ventricular arrhythmia 5 months after, his cardiac function was normal, and transpulmonary valve pressure was 19 mm Hg in the follow-up. The other 7 patients are currently in New York Heart Association functional Class I. Although long-term follow-up is required to explain the durability, the stentless xenograft with a pericardial roll is considered to be an alternative for reconstruction of the RVOT within 2 years after the Ross procedure.