Isabell Hoffmann

Cerebral Protection During Surgery for Acute Aortic Dissection Type A Results of the German Registry for Acute Aortic Dissection Type A (GERAADA)

Background— Cerebral protection during surgery for acute aortic dissection type A relies on hypothermic circulatory arrest, either alone or in conjunction with cerebral perfusion. Methods and Results— The perioperative and intraoperative conditions of 1558 patients submitted from 44 cardiac surgery centers in German-speaking countries were analyzed. Among patients with acute aortic dissection type A, 355 (22.8%) underwent surgery with hypothermic circulatory arrest alone. In 1115 patients (71.6%), cerebral perfusion was used: Unilateral antegrade cerebral perfusion (ACP) in 628 (40.3%), bilateral ACP in 453 (29.1%), and retrograde perfusion in 34 patients (2.2%). For 88 patients with acute aortic dissection type A (5.6%), no circulatory arrest and arch intervention were reported (cardiopulmonary bypass–only group). End points of the study were 30-day mortality (15.9% overall) and mortality-corrected permanent neurological dysfunction (10.5% overall). The respective values for the cardiopulmonary bypass–only group were 11.4% and 9.1%. Hypothermic circulatory arrest alone resulted in a 30-day mortality rate of 19.4% and a mortality-corrected permanent neurological dysfunction rate of 11.5%, whereas the rates were 13.9% and 10.0%, respectively, for unilateral ACP and 15.9% and 11.0%, respectively, for bilateral ACP. In contrast with the ACP groups, there was a profound increase in mortality when systemic circulatory arrest times exceeded 30 minutes in the hypothermic circulatory arrest group (P<0.001). Mortality-corrected permanent neurological dysfunction correlated significantly with perfusion pressure in the ACP groups. Conclusions— This study reflects current surgical practice for acute aortic dissection type A in Central Europe. For arrest times less than 30 minutes, hypothermic circulatory arrest and ACP lead to similar results. For longer arrest periods, ACP with sufficient pressure is advisable. Outcomes with unilateral and bilateral ACP were equivalent.

Influence of operative strategy for the aortic arch in DeBakey type I aortic dissection: analysis of the German Registry for Acute Aortic Dissection Type A.

OBJECTIVE Patients treated with an extensive approach including total aortic arch replacement for acute aortic dissection type A may have a favorable long-term prognosis by treating the residual false lumen. Our goal was to analyze the operative strategy for treatment of type I DeBakey aortic dissection from the German Registry for Acute Aortic Dissection Type A (GERAADA) data. METHODS A total of 658 patients with type I DeBakey aortic dissection and entry only in the ascending aorta were identified in the GERAADA. Patients in group A underwent replacement of the ascending aorta with hemiarch replacement. Patients in group B received extensive treatment with total arch replacement or conventional or frozen elephant trunk. RESULTS A total of 518 patients in group A and 140 patients in group B were treated. There was an overall 30-day mortality of 20.2% (n = 133). Group A had a slightly lower rate of mortality with 18.7% (n = 97) compared with 25.7% for group B (n = 36), but with no statistical significant difference (P = .067). The onset of new neurologic deficit (13.6% in group vs 12.5% in group B, P = .78) and new malperfusion deficit (8.4% in group A vs 10.7% in group B, P = .53) showed no statistical difference. CONCLUSIONS On analysis of the GERAADA data, it seems that a more aggressive approach of aortic arch treatment can be applied without higher perioperative risk even in the onset of acute aortic dissection type A. Long-term follow-up data analysis will be necessary to offer the optimal surgical strategy for different patient groups.

Acute aortic dissection type A: age-related management and outcomes reported in the German Registry for Acute Aortic Dissection Type A (GERAADA) of over 2000 patients.

Objective:To determine the association between age and clinical presentation, management and surgical outcomes in a large contemporary, prospective cohort of patients with acute aortic dissection type A (AADA). Background:AADA is one of the most life-threatening cardiovascular diseases, and delayed surgery or overly conservative management can result in sudden death. Methods:The perioperative and intraoperative conditions of 2137 patients prospectively reported to the multicenter German Registry for Acute Aortic Dissection Type A were analyzed. Results:Of all patients with AADA, 640 (30%) were 70 years or older and 160 patients (7%) were younger than 40 years. The probability of aortic dissection extension to the supra-aortic vessels and abdominal aorta decreased with age (P < 0.0001 and P = 0.0017, respectively). In 1447 patients (69%), the aortic root was preserved and supracoronary replacement of the ascending aorta was done. The probability of this procedure increased with age (P < 0.0001). The incidence of new postoperative neurological disorders was not influenced by age. The lowest probability of 30-day mortality was noted in the youngest patients (11%–14% for patients aged between 20 and 40 years) and rose progressively with age, peaking at 25% in octogenarians. Conclusions:This study reflects current results after surgical treatment of AADA in relation to patient age. Current survival rates are acceptable, even in very elderly patients. The contemporary surgical mortality rate among young patients is lower than that previously reported in the literature. The postoperative stroke incidence does not increase with age.

Cerebral Protection During Surgery for Acute Aortic Dissection Type A

Background— Cerebral protection during surgery for acute aortic dissection type A relies on hypothermic circulatory arrest, either alone or in conjunction with cerebral perfusion. Methods and Results— The perioperative and intraoperative conditions of 1558 patients submitted from 44 cardiac surgery centers in German-speaking countries were analyzed. Among patients with acute aortic dissection type A, 355 (22.8%) underwent surgery with hypothermic circulatory arrest alone. In 1115 patients (71.6%), cerebral perfusion was used: Unilateral antegrade cerebral perfusion (ACP) in 628 (40.3%), bilateral ACP in 453 (29.1%), and retrograde perfusion in 34 patients (2.2%). For 88 patients with acute aortic dissection type A (5.6%), no circulatory arrest and arch intervention were reported (cardiopulmonary bypass–only group). End points of the study were 30-day mortality (15.9% overall) and mortality-corrected permanent neurological dysfunction (10.5% overall). The respective values for the cardiopulmonary bypass–only group were 11.4% and 9.1%. Hypothermic circulatory arrest alone resulted in a 30-day mortality rate of 19.4% and a mortality-corrected permanent neurological dysfunction rate of 11.5%, whereas the rates were 13.9% and 10.0%, respectively, for unilateral ACP and 15.9% and 11.0%, respectively, for bilateral ACP. In contrast with the ACP groups, there was a profound increase in mortality when systemic circulatory arrest times exceeded 30 minutes in the hypothermic circulatory arrest group (P<0.001). Mortality-corrected permanent neurological dysfunction correlated significantly with perfusion pressure in the ACP groups. Conclusions— This study reflects current surgical practice for acute aortic dissection type A in Central Europe. For arrest times less than 30 minutes, hypothermic circulatory arrest and ACP lead to similar results. For longer arrest periods, ACP with sufficient pressure is advisable. Outcomes with unilateral and bilateral ACP were equivalent.

Supracoronary ascending aortic replacement in patients with acute aortic dissection type A: What happens to the aortic root in the long run?

OBJECTIVE Our objective was to determine long-term outcome predictors for patients with acute aortic dissection type A (AADA) and aortic root involvement. METHODS From 2001 through 2009, 119 of 152 patients operated on for AADA at a tertiary medical center underwent supracoronary ascending aortic replacement (52 women; mean age, 61 ± 15 years). Those with at least 1-year follow-up (n = 97) were retrospectively assessed for preoperative aortic root disease. Follow-up data were assessed for evidence of new-onset aortic root disease by computed tomography and echocardiography, and for reoperation for aortic root disease. RESULTS Median follow-up was 33.8 months (range, 0-112 months). Twenty-six (27%) patients had new-onset aortic root disease at 4.4 ± 2.6 years after the initial procedure (range, 1.0-8.2 years) and 10 required aortic root reoperation. Severe aortic dissection with extension to pelvic arteries was an independent predictor for new-onset aortic root disease (P < .01). Dissection of all aortic sinuses during the initial procedure was an independent predictor (P < .05) for aortic root reoperation. Mean rate of aortic root expansion after supracoronary repair was 0.6 ± 1.1 mm per year. Preoperative aortic root diameter and aortic sinus dissection did not affect survivals. Five-year survivals were similar in patients with and without new-onset aortic root disease (91% vs 89%; P = .79). CONCLUSIONS In patients with AADA, dissection of 3 aortic sinuses is an independent predictor for need of reoperation, whereas dissection extension into the iliac arteries is a predictor of secondary aortic root disease. Long-term follow-up at close intervals is warranted in patients with supracoronary ascending aortic replacement to reduce mortality caused by new onset of aortic root disease.

Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA)

OBJECTIVES Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death. METHODS Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters on 30-day mortality. RESULTS Overall 30-day mortality (16.9%) increased with age [adjusted odds ratio (OR) = 1.121] and among patients who were comatose (adjusted OR = 3.501) or those who underwent cardiopulmonary resuscitation (adjusted OR = 3.751; all P < 0.0001). The higher the number of organs that were malperfused, the risk for death was (adjusted OR for one organ = 1.651, two organs = 2.440, three organs or more = 3.393, P < 0.0001). Mortality increased with longer operating times (total, cardiopulmonary bypass, cardiac ischaemia and circulatory arrest; all P < 0.02). Arterial cannulation site for extracorporeal circulation, operative techniques and arch interventions had no significant impact on 30-day mortality (all P > 0.1). No significant risk factors, but relevant increases in mortality, were determined in patients suffering from hemiparesis pre- and postoperatively (each P < 0.01), and in patients experiencing paraparesis after surgery (P < 0.02). CONCLUSIONS GERAADA could detect significant disease- and surgery-related risk factors for death in AADA, influencing the outcome of surgically treated AADA patients. Comatose and resuscitated patients have the poorest outcome. Cannulation sites and operative techniques did not seem to affect mortality. Short operative times are associated with better outcomes.

Iatrogenic acute aortic dissection type A: insight from the German Registry for Acute Aortic Dissection Type A (GERAADA)

OBJECTIVES Previous investigators have reported a grave prognosis for iatrogenic acute aortic dissection (iAADA), but such studies are limited by their small sample sizes. The purpose of the current study was to analyse the clinical characteristics, current management and surgical outcomes in a large number of iAADA patients identified through a multicentre registry. METHODS Between July 2006 and June 2010, 50 centres participated in the German Registry for Acute Aortic Dissection Type A (GERAADA). Of the 2137 patients included, 100 (5%) had iAADA. We compared the clinical features and 30-day outcomes of patients with iatrogenic and spontaneous acute aortic dissection type A (sAADA). RESULTS Patients with iAADA were older than those with sAADA (67.7 ± 9.4 vs 60.1 ± 13.7 years, P < 0.0001). Preoperative cardiac tamponade and hemiplegia or hemiparesis were less frequently observed in patients with iAADA (10 vs 21%, P = 0.003; 1 vs 7%, P = 0.04). Aortic dissection extended to the supra-aortic vessels (19 vs 38%, P = 0.0005) and to iliac arteries (7 vs 25%, P = 0.0002) less frequently in iAADA patients. Those with iAADA were less likely to undergo complex aortic surgery with composite graft implantation (8 vs 20%, P = 0.02), hemiarch (38 vs 47%, P = 0.04) or total arch replacement (9 vs 17%, P = 0.07). The rate of new onset of hemiplegia or hemiparesis after surgery was also lower in iAADA patients (4 vs 10%, P = 0.05). Thirty-day mortality did not differ between the two groups (16 vs 17% for iAADA vs sAADA, P = 0.53). CONCLUSIONS Early-term surgical outcomes in current iAADA patients are better than those reported previously. Immediate surgical therapy results in acceptable outcomes similar to those in naturally occurring aortic dissection.

The power of DNA double-strand break (DSB) repair testing to predict breast cancer susceptibility

Most presently known breast cancer susceptibility genes have been linked to DSB repair. To identify novel markers that may serve as indicators for breast cancer risk, we performed DSB repair analyses using a case‐control design. Thus, we examined 35 women with defined familial history of breast and/or ovarian cancer (first case group), 175 patients with breast cancer (second case group), and 245 healthy women without previous cancer or family history of breast cancer (control group). We analyzed DSB repair in peripheral blood lymphocytes (PBLs) by a GFP‐based test system using 3 pathway‐specific substrates. We found increases of microhomology‐mediated nonhomologous end joining (mmNHEJ) and nonconservative single‐strand annealing (SSA) in women with familial risk vs. controls (P=0.0001‐0.0022) and patients with breast cancer vs. controls (P=0.0004‐0.0042). Young age (<50) at initial diagnosis of breast cancer, which could be indicative of genetic predisposition, was associated with elevated SSA using two different substrates, amounting to similar odds ratios (ORs=2.54‐4.46, P= 0.0059‐0.0095) as for familial risk (ORs=2.61‐4.05, P=0.0007‐0.0045). These findings and supporting validation data underscore the great potential of detecting distinct DSB repair activities in PBLs as method to estimate breast cancer susceptibility beyond limitations of genotyping and to predict responsiveness to therapeutics targeting DSB repair‐dysfunctional tumors.—Keimling, M., Deniz, M., Varga, D., Stahl, A., Schrezenmeier, H., Kreienberg, R., Hoffmann, I., König, J., Wiesmüller, L. The power of DNA double‐strand break (DSB) repair testing to predict breast cancer susceptibility. FASEB J. 26, 2094‐2104 (2012). www.fasebj.org

Influence of operative strategy for the aortic arch in DeBakey type I aortic dissection - analysis of the German Registry for Acute Aortic Dissection type A (GERAADA)

Acute aortic dissection type A (AADA) remains a life threatening medical condition requiring emergent surgical therapy. Despite improvements in diagnostics, medical therapy and surgical technique, patient mortality and morbidity remains high (1). Standard treatment in the setting of AADA is the replacement of the ascending aorta with resection of the entry site, often in combination with an open distal anastomosis or hemiarch replacement, during a period of circulatory arrest with implementation of adjunct neuroprotective strategies such as cerebral perfusion and hypothermia (2). However, this treatment leaves the downstream aorta untouched and a residual dissection membrane remains in up to 70% of patients treated for AADA (3-7). The risk of progressive dilation with possible need for aortic re-intervention over the long-term remains (8-11). Due to this risk, a more aggressive approach with complete arch replacement and possible stenting of the proximal descending aorta via an antegrade approach has been adopted by a number of clinical institutions worldwide, to better obliterate the false lumen and thus reduce the incidence of late aortic complications (12-14). Other groups, however, have demonstrated an increased risk of mortality and morbidity when extensive surgery involving the aortic arch and the downstream aorta is implemented, thus recommending a more conservative approach to the treatment of AADA patients (15,16). The German Registry for Acute Aortic Dissection type A (GERAADA) is a web-based registry, initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery. It is presently the largest registry worldwide documenting patients undergoing surgery for AADA (17-19). Analysis of GERAADA gave us the opportunity to compare the surgical outcomes of patients with DeBakey type I dissection treated by total arch replacement and those of hemiarch replacement with respect to early mortality, and onset of new neurological and malperfusion deficit.

Participation in adjuvant clinical breast cancer trials: Does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9433 patients

UNLABELLED Adjuvant clinical trials (CTs) usually compare a standard treatment regime versus an innovative new substance or regimen. Participation in CT however, is available for only few patients and exclusion criteria are usually very strict. Therefore we used an unselected patient cohort to investigate the following questions: MATERIAL AND METHODS This German retrospective multi-centre cohort study included 9433 patients with primary breast cancer recruited from 1992 to 2008. RESULTS One thousand two hundred and fifty-five (13.3%) patients participated in adjuvant clinical trials (PA) and 8178 (86.7%) did not (NPA). RFS was higher among participants (PA) than among non-participants (NPA) [p=0.006], but differences in overall survival (OAS) were not significant [p=0.15]. When stratified for guideline adherence, the outcome was not different for guideline conform NPA [RFS: p=0.88] [OAS: p=0.37] compared to PA. Survival parameters however, were significantly poorer in non-guideline conform PA [RFS: p<0.001] [OAS: p<0.001] and non-guideline conform NPA [RFS: p<0.001] [OAS: p<0.001] as compared to guideline adherent PA. DISCUSSION There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials tended to higher survival rates, but only if guideline-adherent treatment was applied. Patients who do not have access to clinical trials may profit substantially from guideline-adherent adjuvant treatment.