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ABSTRACT: OBJECTIVESA prospective randomized multicentre trial was performed to analyse the efficacy of a vest (Posthorax support vest®) to prevent sternal wound infection after cardiac surgery, and to identify risk factors.METHODS
From September 2007 to March 2010, 2539 patients undergoing cardiac surgery via median sternotomy were prospectively randomized into those who received a Posthorax® vest and those who did not. Patients were instructed to wear the vest postoperatively for 24 h a day for at least 6 weeks; the duration of follow-up was 90 days. Patients who did not use the vest within a period of 72 h postoperatively were regarded as study dropouts. Statistical calculations were based on an intention-to-treat (ITT) analysis. Further evaluations comprised all subgroups of patients.RESULTSComplete data were available for 2539 patients (age 67 ± 11years, 45% female). Of these, 1351 were randomized to receive a vest, while 1188 received no vest. No significant differences were observed between groups regarding age, gender, diabetes, body mass index, chronic obstructive pulmonary disease (COPD), renal failure, the logistic EuroSCORE and the indication for surgery. The frequency of deep wound complications (dWC: mediastinitis and sternal dehiscence) was significantly lower in vest (n = 14; 1.04%) vs non-vest (n = 27; 2.27%) patients (ITT, P < 0.01), but superficial complications did not differ between groups. Subanalysis of vest patients revealed that only 933 (Group A) wore the vest according to the protocol, while 202 (Group BR) refused to wear the vest (non-compliance) and 216 (Group BN) did not use the vest for other reasons. All dWC occurred in Groups BR (n = 7) and BN (n = 7), although these groups had the same preoperative risk profile as Group A. Postoperatively, Group BN had a prolonged intubation time, a longer stay in the intensive care unit, greater use of intra-aortic balloon pump, higher frequency of COPD and a larger percentage of patients who required prolonged surgery.CONCLUSION
Consistent use of the Posthorax® vest prevented deep sternal wounds. The anticipated risk factors for wound complications did not prove to be relevant, whereas intra- and postoperative complications appear to be very significant.
Interactive cardiovascular and thoracic surgery 06/2013;
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ABSTRACT: Thoracic endovascular aortic repair has broadened the spectrum of treatment options for various acute and chronic thoracic aortic diseases. In clinical practice, aneurysms of the descending aorta are rarely limited to 1 segment. Thus, various surgical and endovascular options have been developed to offer treatment to those patients with more extended descending thoracic aortic disease. We have summarized the most common methods of arch rerouting, depending on the aortic involvement, emphasizing that these techniques should be used very selectively by experienced cardiovascular surgery teams.
The Journal of thoracic and cardiovascular surgery 12/2012; · 3.41 Impact Factor
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Martin Czerny,
Jean Bachet,
Joseph Bavaria,
Robert S Bonser,
Michael A Borger,
Ruggero De Paulis,
Roberto Dibartolomeo, Martin Grabenwöger,
Lars Lonn,
Mahmood Loubani,
Carlos A Mestres,
Marc A A M Schepens,
Ernst Weigang,
Thierry P Carrel
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ABSTRACT: At least every ten years, each specialty should reflect upon its past, its present and its future, in order to be able to reconfirm the direction in which it is headed, to adopt suggestions from inside and outside and, consequently, to improve. As such, the aim of this manuscript is to provide the interested reader with an overview of how aortic surgery and (perhaps more accurately) aortic medicine has evolved in Europe, and its present standing; also to provide a glimpse into the future, trying to disseminate the thoughts of a group of people actively involved in the development of aortic medicine in Europe, namely the Vascular Domain of the European Association of Cardio-Thoracic Surgery (EACTS).
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 11/2012; · 2.40 Impact Factor
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Martin Grabenwöger,
Fernando Alfonso,
Jean Bachet,
Robert Bonser,
Martin Czerny,
Holger Eggebrecht,
Arturo Evangelista,
Rossella Fattori,
Heinz Jakob,
Lars Lönn,
Christoph A Nienaber,
Guido Rocchi,
Hervè Rousseau,
Matt Thompson,
Ernst Weigang,
Raimund Erbel
European Heart Journal 05/2012; 33(13):1558-63. · 10.48 Impact Factor
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Martin Grabenwöger,
Fernando Alfonso,
Jean Bachet,
Robert Bonser,
Martin Czerny,
Holger Eggebrecht,
Arturo Evangelista,
Rossella Fattori,
Heinz Jakob,
Lars Lönn,
Christoph A Nienaber,
Guido Rocchi,
Hervè Rousseau,
Matt Thompson,
Ernst Weigang,
Raimund Erbel
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2012; 42(1):17-24. · 2.40 Impact Factor
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ABSTRACT: The goal of the retrospective study was to relate the site of the primary entry tear in acute type B aortic dissections to the presence or development of complications.
A consecutive series of 52 patients referred with acute type B aortic dissection was analysed with regard to the location of the primary entry tear (convexity or concavity of the distal aortic arch) using the referral CT scans at the time of diagnosis. These findings were related to the clinical outcome as well as to the need for intervention.
Twenty-five patients (48%) had the primary entry tear located at the convexity of the distal aortic arch, whereas 27 patients (52%) had the primary entry tear located at the concavity of the distal aortic arch. Twenty per cent of patients with the primary entry tear at the convexity presented with or developed complications, whereas 89% had or developed complications with the primary entry tear at the concavity (P < 0.001). Furthermore, in patients with complicated type B aortic dissection, the distance of the primary entry tear to the left subclavian artery was significantly shorter as in uncomplicated patients (8 vs. 21 mm; P = 0.002). In Cox regression analysis, a primary entry tear at the concavity of the distal aortic arch was identified as an independent predictor of the presence or the development of complicated type B aortic dissection.
A primary entry tear at the concavity of the aortic arch as well as a short distance between the primary entry tear and the left subclavian artery are frequently associated with the presence or the development of complicated acute type B aortic dissection. These findings shall help us to further differentiate acute type B aortic dissections in addition to the common categorization in complicated and uncomplicated. These findings may therefore also have an impact on primary treatment.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2012; 42(3):571-6. · 2.40 Impact Factor
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Robert S Bonser,
Aaron M Ranasinghe,
Mahmoud Loubani,
Jonathan D Evans,
Nassir M A Thalji,
Jean E Bachet,
Thierry P Carrel,
Martin Czerny,
Roberto Di Bartolomeo, Martin Grabenwöger,
Lars Lonn,
Carlos A Mestres,
Marc A A M Schepens,
Ernst Weigang
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ABSTRACT: Acute type A aortic dissection is a lethal condition requiring emergency surgery. It has diverse presentations, and the diagnosis can be missed or delayed. Once diagnosed, decisions with regard to initial management, transfer, appropriateness of surgery, timing of operation, and intervention for malperfusion complications are necessary. The goals of surgery are to save life by prevention of pericardial tamponade or intra-pericardial aortic rupture, to resect the primary entry tear, to correct or prevent any malperfusion and aortic valve regurgitation, and if possible to prevent late dissection-related complications in the proximal and downstream aorta. No randomized trials of treatment or techniques have ever been performed, and novel therapies-particularly with regard to extent of surgery-are being devised and implemented, but their role needs to be defined. Overall, except in highly specialized centers, surgical outcomes might be static, and there is abundant room for improvement. By highlighting difficulties and controversies in diagnosis, patient selection, and surgical therapy, our over-arching goal should be to enfranchise more patients for treatment and improve surgical outcomes.
Journal of the American College of Cardiology 12/2011; 58(24):2455-74. · 14.16 Impact Factor
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ABSTRACT: Sternal instability, dehiscence and mediastinitis are major causes of morbidity and mortality in cardiac surgery. The aim of this analysis is to determine the effect of a Posthorax support vest (Epple Inc, Vienna, Austria) after median sternotomy. One thousand five hundred and sixty cases were included in a prospective randomized multicenter trial. Patients were randomized as follows: 905 received a flexible dressing postoperatively (group A) and 655 patients were given a Posthorax support vest (group B). Patients in groups A and B were well matched. Their mean age was 68 years (range: 34-87 years). The patient characteristics and operative data were equally distributed in both groups. The mean total hospital stay was significantly shorter in group B than in group A (A: 17.33+/-17.5; B: 14.76+/-7.7; P=0.04). Sternal wound complications necessitating reoperation during the 90 days follow-up period were observed in 4.5%. Reoperation rates were as follows: 3.9% in group A and 0.6% in group B (P<0.05). The use of the Posthorax sternum support vest is a valuable adjunct to prevent sternum-related complications after cardiac surgery. In the 90 days follow-up period, additional surgical procedures were significantly reduced by the use of the support vest.
Interactive cardiovascular and thoracic surgery 05/2010; 10(5):714-8.
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The Journal of heart valve disease 11/2009; 18(6):730-1. · 0.81 Impact Factor
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The Journal of heart valve disease 06/2009; 18(3):352-3. · 0.81 Impact Factor
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Rossella Fattori,
Christoph A Nienaber,
Hervé Rousseau,
Jean-Paul Beregi,
Robin Heijmen, Martin Grabenwöger,
Philippe Piquet,
Luigi Lovato,
Chaouki Dabbech,
Stephan Kische,
Virginia Gaxotte,
Marc Schepens,
Marek Ehrlich,
Jean-Michelle Bartoli
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ABSTRACT: Endovascular treatment of thoracic aortic diseases demonstrated low perioperative morbidity and mortality when compared with conventional open repair. Long-term effectiveness of this minimally invasive technique remains to be proven. The Talent Thoracic Retrospective Registry was designed to evaluate the impact of this therapy on patients treated in 7 major European referral centers over an 8-year period.
Data from 457 consecutive patients (113 emergency and 344 elective cases) who underwent endovascular thoracic aortic repair with the Medtronic Talent Thoracic stent graft (Medtronic/AVE, Santa Rosa, Calif) were collected. Follow-up analysis (24 +/- 19.4 months, range 1-85.1 months) was based on clinical and imaging findings, including all adverse events. To ensure consistency of data interpretation and event reporting, one physician reviewed all adverse events and deaths for the whole cohort of patients. In the case of discrepancies, the treating physicians were queried.
Among 422 patients who survived the interventional procedure (in-hospital mortality 5%, 23 patients), mortality during follow-up was 8.5% (36 patients), and in 11 of them the death was related to the aortic disease. Persistent endoleak was reported at imaging follow-up in 64 cases: 44 were primary (9.6%) and 21 occurred during follow-up (4.9%). Seven patients with persistent endoleak had aortic rupture during follow-up, at a variable time from 40 days to 35 months, and all subsequently died. A minor incidence of migration of the stent graft (7 cases), graft fabric alteration (2 cases), and modular disconnection (3 cases) was observed at imaging. Kaplan-Meier overall survival estimate at 1 year was 90.97%, at 3 years was 85.36%, and at 5 years was 77.49%. At the same intervals, freedom from a second procedure (either open conversion or endovascular) was 92.45%, 81.3%, and 70.0%, respectively.
Endovascular treatment for thoracic aortic disease with the Talent stent graft is associated with low early morbidity and mortality rates also for patients who are at high risk and treated on an emergency basis. Follow-up data indicate a substantial durability of the procedure with a high freedom from related death and secondary interventions.
The Journal of thoracic and cardiovascular surgery 09/2006; 132(2):332-9. · 3.41 Impact Factor
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Maria Schoder, Martin Grabenwöger,
Thomas Hölzenbein,
Manfred Cejna,
Marek P Ehrlich,
Thomas Rand,
Alfred Stadler,
Martin Czerny,
Christoph M Domenig,
Christian Loewe,
Johannes Lammer
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ABSTRACT: The purpose of the study was to determine technical and clinical results in endovascular repair of thoracic aortic diseases necessitating stent-graft anchoring across the arch vessels.
The causes for endovascular treatment in 58 patients (aged 20 to 84 years) were aneurysms (n = 32), acute type A (n = 2) and type B dissections (n = 17), posttraumatic transections (n = 4), iatrogenic dissection (n = 1), and penetrating ulcers with an intramural hematoma (n = 2). Surgical revascularization of arch vessels was performed in 26 patients before stent-graft implantation. Intentional overstenting of the left subclavian artery resulted in complete occlusion in 8 and was partial in 24 patients.
The 30-day mortality rate was 3.4%. Overall, 19 major postprocedural complications occurred in 14 (24%) patients. Among patients with left subclavian artery occlusion, 2 patients had major (1 paraplegia, 1 critical arm ischemia), and 3 minor (2 temporary vertebrobasilary symptoms, 1 transient arm claudication) complications. Fourteen (25%) patients had an early endoleak, of whom 5 were treated successfully with a secondary endovascular procedure, 2 necessitated open surgical conversion, and 7 were treated conservatively, with spontaneous sealing of the endoleak in 3. In 53 (91%) in whom computed tomographic follow-up was longer than 3 months (mean, 30.1 months, range, 3 to 85), the aortic diameter along the stented segment decreased in 24, was stable in 19, and increased in 10 patients.
Fixation of the stent graft in the aortic arch can expand the applicability of endovascular repair. Intentional overstenting should be performed with caution to avoid ischemic problems after complete occlusion of left subclavian artery.
The Journal of thoracic and cardiovascular surgery 03/2006; 131(2):380-7. · 3.41 Impact Factor
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ABSTRACT: Predictors of adverse outcome after replacement of the ascending aorta with resection of the intimal tear and open distal anastomosis were analyzed in 167 patients (109 male, median age 56). Median hypothermic circulatory arrest (HCA) time was 30 minutes (range 12 to 113). Eighty-six patients (pts) had surgery within 24 hours and 81 within 72 hours of symptom onset. Thirty-seven pts had only ascending aortic replacement, 128 had hemiarch repair, and in 2 the entire arch was replaced. The aortic valve was replaced in 37 pts, resuspended in 116, and untouched in 14. Either death or permanent neurological dysfunction was considered an adverse outcome (AO). AO occurred in 30.5% (51/167) of patients overall. Multivariate analysis revealed that the only significant (P<0.05) independent preoperative predictor of AO was hemodynamic instability (OR 6.0). Transient neurological dysfunction (TND) occurred in 19 of 116 patients (16.4%). Significant predictors of TND were increasing age >60 (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and coronary heart disease (OR 3.4). Cumulative survival of patients (median follow-up 34 months) was 55% at 1, 49% at 5, and 44% at 8 years, indicating an excessive in-hospital mortality, but excellent long term outcome. Surgical treatment of acute type A dissections is still associated with a high incidence of adverse outcome, but results in excellent long-term survival. Earlier diagnosis, before the development of cardiac tamponade and hemodynamic compromise, is critical to improve the operative salvage rate.
Circulation 09/2003; 108 Suppl 1:II318-23. · 14.74 Impact Factor
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Maria Schoder,
Fabiola Cartes-Zumelzu, Martin Grabenwöger,
Manfred Cejna,
Martin Funovics,
Claus G Krenn,
Doris Hutschala,
Florian Wolf,
Siegfried Thurnher,
Georg Kretschmer,
Johannes Lammer
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ABSTRACT: The purpose of this study was to evaluate the clinical and midterm results after endovascular treatment of atherosclerotic thoracic aortic aneurysms.
Twenty-eight consecutive patients who were 53-82 years old (mean age, 71.6 years) were treated with a commercially available endoprosthesis. Subclavian transposition or bypass surgery was performed before the procedure in eight patients. Size dynamics of the aneurysms were analyzed on the basis of diameter and thrombus volume measurements obtained on three-dimensional CT reconstructions before hospital discharge (n = 22) and at the 1-year (n = 22), 2-year (n = 12), and 3-year (n = 5) follow-ups.
The technical success rate was 100%. There was no 30-day mortality. None of the patients had symptoms due to spinal cord ischemia. The survival rate at 1, 2, and 3 years was 96.1%, 90.9%, and 80.2%, respectively. During the perioperative period, patients presented with leukocytosis (37%), fever (36%), elevated C-reactive protein value (92%), pleural effusion (50%), and periaortic atelectasis (41%). Three early type I endoleaks sealed spontaneously. Three early type II endoleaks persisted over time, and one late type II endoleak was detected. In patients with type II endoleaks, thrombus volume of the aneurysms was constant (n = 2) or increased (n = 2). In patients without endoleaks, mean thrombus volume decreased (-53.2 +/- 56.8 mL, -40%) significantly (p = 0.001) during the first year. There was no significant interval decrease between the 1- and 2-year follow-ups (mean, -2.4 mL, p = 0.92) and between the 2- and 3-year follow-ups (mean, -0.4 mL, p = 0.68).
Endovascular treatment of atherosclerotic thoracic aortic aneurysms may result in a substantial reduction of the aneurysm sac in patients without endoleaks.
American Journal of Roentgenology 04/2003; 180(3):709-15. · 2.78 Impact Factor
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ABSTRACT: To report our initial experience with endovascular stent-graft repair of complicated penetrating atherosclerotic ulcers as an alternative to surgery in patients with increased risk of perioperative morbidity and mortality.
During a 2-year period, eight patients with complicated penetrating atherosclerotic ulcers of the descending thoracic aorta were treated with the Gore Excluder stent-graft. Patients (mean age, 70.6 years) presented with two to five comorbid conditions causing an increased risk for surgical repair. In addition to painful events, three patients presented with severe hemoptysis, one patient with shortness of breath, and one patient with dysphagia. All patients underwent emergency computed tomography, and diagnosis of contained rupture was confirmed in five patients. Computed tomographic findings included one to three penetrating ulcers per patient (n = 4), pseudoaneurysms (n = 5), additional intramural hematomas (n = 4), mediastinal bleeding (n = 2), and hematothoraces (n = 4). Through an iliac or femoral access site, a total of 11 stent-grafts were implanted under general (n = 5), epidural (n = 2), or spinal (n = 1) anesthesia.
Deployment of stent-grafts was successful in all patients, and all sites of hemorrhage were sealed. The intramural hematoma resolved completely in three cases, and two pseudoaneurysms decreased in size. Intentional occlusion of the origin of left subclavian artery with the stent-graft in one patient was tolerated without left arm or cerebral symptoms. One patient experienced permanent paraplegia immediately after endovascular repair. There were no deaths during the hospital stay (range, 7-35 days; mean, 14.5 days). One patient was lost to follow-up after hospital discharge. The clinical observation period for the remaining seven patients was 38 to 99 weeks (mean, 60 weeks).
Endovascular stent-graft repair in complicated penetrating atherosclerotic ulcers is an alternative therapeutic option to conventional thoracotomy, especially in patients at high risk of increased morbidity and mortality perioperatively and postoperatively.
Journal of Vascular Surgery 11/2002; 36(4):720-6. · 3.21 Impact Factor
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ABSTRACT: Open surgical repair is considered the traditional treatment for patients with thoracic aortic aneurysms (TAA). In view of the persistent perioperative mobidity and mortality, endovascular stent-graft placement as a minimally invasive and potentially safer treatment for aneurysm of the descending aorta was introduced in 1992. Since then, progress has been made and several institutions have substantiated the safety and effectiveness of stent grafts in the repair of descending TAAs or type-B aortic dissections. Currently, both custom-designed, home-made, and commercially available stent grafts are used. Prior to placement of the endoprosthesis, three major prerequisites must be considered: the localization and morphology of the aneurysm; the distal vascular access of sufficient size; and a limited tortuosity of the abdominal and thoracic aorta. Although short-term results are encouraging, severe complications, including paraplegia, cerebral strokes, and aortic rupture, have been encountered. The long-term durability of currently available stent-graft systems is nonexistent and material fatigue are of major concern to both surgeons and radiologists. Nevertheless, endovascular stent-graft placement could become the procedure of choice in a substantial number of patients with descending TAA.
European Radiology 07/2002; 12(6):1370-87. · 3.22 Impact Factor
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ABSTRACT: The association of acute-phase reaction and outcome of patients with acute vascular diseases is controversial. The prognostic value of admission C-reactive protein (CRP) in patients with acute aortic aneurysm or dissection has not yet been investigated.
Cohort study including 255 consecutive patients from an aneurysm registry with symptomatic thoracic or abdominal aortic aneurysm and/or dissection in an emergency department of a tertiary care university hospital.
Patients were included who had symptoms of aortic disease admitted between 1 January 1992 and 31 November 1998 and were followed up until 31 December 1999 for survival.
Admission CRP (mg/dl) levels were categorized in quartiles: quartile 1, less than 0.5; quartile 2, 0.50-1.30; quartile 3, 1.31-6.30; quartile 4, higher than 6.30. Each group contained about 60 patients.
Cumulative mortality 1, 3, and 6 months after presentation was 32%, 37%, and 40%, respectively. Increased CRP levels were independently associated with mortality, adjusted for age, sex, hemodynamic shock, mechanical ventilation, coronary artery disease, aortic rupture, hemoglobin, diabetes, and treatment strategy (surgery vs. conservative). Hazard ratios in patients with CRP levels in quartiles 2-4 compared to quartile 1 were 0.7, 1.8, and 2.6, respectively.
Elevated admission CRP values in patients with symptomatic aortic aneurysm/dissection were independently associated with poor prognosis. CRP levels higher than 6.3 mg/dl indicate a high risk for short-term mortality.
Intensive Care Medicine 07/2002; 28(6):740-5. · 5.40 Impact Factor
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Journal of Thoracic and Cardiovascular Surgery 06/2002; 123(5):1003-5. · 3.41 Impact Factor
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Marek P Ehrlich, Martin Grabenwöger,
Juliane Kilo,
Alfred A Kocher,
Georg Grubhofer,
Andrea M Lassnig,
Edda M Tschernko,
Bernhard Schlechta,
Doris Hutschala,
Hans Domanovits,
Gottfried Sodeck,
Ernst Wolner
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ABSTRACT: The purpose of this study was to evaluate the significance of aortic rupture on clinical outcome in patients after aortic repair for acute type A dissection.
One hundred and twenty patients underwent aortic operations with resection of the intimal tear and open distal anastomosis. Median age was 60 years (range 16 to 87); 78 were male. Thirty-six patients had only ascending aortic replacement, 82 had hemiarch repair, and 2 had the entire arch replaced. Retrograde cerebral perfusion was utilized in 66 patients (53%). Rupture defined as free blood in the pericardial space was present in 60 patients (50%). Univariate and multivariate analyses were performed to assess the risk factors for mortality and neurologic dysfunction.
Overall hospital mortality rate was 24.2% +/- 4.0% (+/- 70% confidence level) but did not differ between patients with aortic rupture or without (p = 0.83). The incidence of permanent neurologic dysfunction was 9.4% overall, 10.5% with rupture and 8.3% without rupture (p = 0.75). Multivariate analysis revealed absence of retrograde cerebral perfusion and any postoperative complication as statistically significant indicators for in-hospital mortality (p < 0.05). Overall 1- and 5-year survival was 85.3% and 33.7%; among discharged patients, survival in the nonruptured group was 89% and 37%, versus 81% and 31% in the ruptured group (p = 0.01).
Aortic rupture at the time of surgery does not increase the risk of hospital mortality or permanent neurologic complications in patients with acute type A dissections. However, aortic rupture at the time of surgery does influence long-term survival.
The Annals of Thoracic Surgery 06/2002; 73(6):1843-8. · 3.74 Impact Factor
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ABSTRACT: Background. This study was performed to evaluate the safety and feasibility of endovascular stent graft placement in the treatment of descending thoracic aortic aneurysms.Methods. Between November 1996 and February 1999, endovascular stent graft repair was used in 21 patients. There were 5 women and 16 men with a mean age of 67 years (range, 41 to 87 years). An atherosclerotic aneurysm with a diameter of more than 6 cm was the indication for intervention in 19 patients (90.5%). In 2 patients (9.5%), a localized aortic dissection with a diameter of more than 6 cm was treated. In 71.4% (15 of 21) of patients, multiple stents were necessary for aneurysm exclusion. To allow safe deployment of the stent graft, preliminary subclavian–carotid artery transposition was performed in 9 patients (42.9%). Vascular access was achieved through a small incision in the abdominal aorta (n = 6), an iliac artery (n = 8), or a femoral artery (n = 7). Talent and Prograft stent grafts were used.Results. Successful deployment of the endovascular stent grafts was achieved in all patients. Two patients died postoperatively (mortality rate, 9.5%), 1 of aneurysmal rupture and the other of impaired perfusion of the celiac axis. Repeat stenting was done in 3 patients because of intraoperative leakage.Conclusions. Endovascular stent graft repair is a promising and less invasive alternative to exclude the aneurysm from blood flow. This technique allows treatment of patients who are unsuitable for conventional surgical procedures. An exact definition of inclusion criteria and technical development of stent grafts should contribute to further improvements in clinical results.
The Annals of Thoracic Surgery 03/2000; · 3.74 Impact Factor