Aortic events and relative survival in patients with moderately dilated proximal thoracic aorta.

Objectives. This study describes growth, local and remote aortic events, and survival in patients with proximal (root, ascending) aortic diameters just below threshold for operation. Methods. Patients with proximal aortic diameter of 4.5 to 5.4 cm at baseline, were followed with serial computed tomography studies and data collected retrospectively. Aortic growth rate was estimated using mixed effects modelling. Clinical and radiological features associated with outcomes (all-cause death, aortic death, local or remote aortic events (dissection, rupture, intramural hematoma, or intervention)) were assessed with Cox analysis. Survival and freedom from events were estimated using Kaplan-Meier methods. Results. 80 patients underwent 274 CT scans during 265 patient-years. Median proximal aortic growth was 0.2 cm in 3 years. 32 events occurred in 28 patients (35%). Eleven events were local, all elective proximal aortic surgery. Nine events were remote: 5 type B aortic dissections, 3 descending aneurysms undergoing elective repair, and one infrarenal aortic rupture. Twelve patients died, half of type B aortic dissection. Relative survival compared to a matched normal population was 82% (95% confidence limits 55-98%) at 10 years. In Cox analysis, increased descending aortic diameter was an independent predictor of all-cause death (hazard ratio [HR], 1.39) and aortic death (HR 1.96). Conclusions. Descending, but not proximal, aortic growth was predictive of lethal events. The decreased relative survival, the substantial number of remote aortic events and aortic deaths strongly suggest continuous serial CT surveillance of the entire aorta. Other indicators than proximal aortic diameter appear needed to improve management of this patient group.

Improving outcomes of surgery for acute type A aortic dissection.

Background. It remains equivocal if acute type A aortic dissection (ATAAD) surgical outcomes are improving. We analyzed current outcome trends to evaluate improvements and to identify predicting variables. Methods. From 2015 to 2020, 204 patients underwent surgery for ATAAD and were divided into recent (n = 102) and earlier (n = 102) groups. Uni- and multivariable statistical analysis was performed to identify predictors of 30-day mortality. Results. Thirty-day mortality decreased significantly in the recent group (3.9% vs 14.6%, p = .014). Prevalence of neurological insult also decreased significantly (13% vs 25%, p = .028). Other major complications remained unchanged. There was no statistically significant difference in overall 30-day mortality between low-volume vs high-volume surgeons (12.3% vs 7.3%, p = .21). The number of surgeons performing ATAAD procedures decreased from nine in 2015 to five in 2020. Preoperative lactate (OR 1.24, 95%CI 1.03-1.51), dissection of any arch vessel (OR 14.2, 95%CI 1.79-113), non-normal left ventricular ejection fraction (OR 12.5, 95%CI 2.54-61.6), biological composite graft (OR 19.1, 95%CI 2.75-133), concomitant coronary artery bypass grafting (OR 38.8, 95%CI 2.91-517) and intraoperative adverse event (OR 9.5, 95%CI 2.22-40.9) were statistically significant independent predictors of mortality. Conclusions. Early outcomes after ATAAD improved in the most recent experience. Part of the explanation may be fewer surgeons performing more procedures annually, a relatively conservative approach to the extent of aortic resection and ensuring adequate cerebral protection. Major complications remain prevalent and require attention to be further reduced.

Outcomes of descending and thoracoabdominal aortic repair in connective tissue disorder patients.

OBJECTIVES: Open surgical repair (OSR) of descending and thoracoabdominal aortic aneurysms carries risks of mortality and major complications. Patients with connective tissue disorders (CTD) are younger and require safe, efficient treatment with long-term durability. This study provides current outcome data to help inform treatment decisions. METHODS: All OSRs of descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm (TAAA) from January 2011 to July 2021 were included in a retrospective cohort study. Primary outcome measures were early and follow-up mortality and reintervention. Secondary outcome measures were major complications. Kaplan-Meier methods were used to estimate reintervention-free survival. RESULTS: A total of 26 OSRs (7 DTAA, 19 TAAA) were performed in 23 patients: 20 (77%) Marfan and 6 (23%) Loeys-Dietz syndrome; median age 43 years. Aortic dissection was present in 100% and 3/26 (12%) were urgent. Early mortality was 1/26 (3.8%). No patient suffered spinal cord ischemia, stroke, vocal cord paralysis, or re-exploration for bleeding. The transient respiratory failure occurred in 19% (5/26) and transient renal replacement therapy in 15% (4/26). Renal function normalized in all patients within 3 months. During follow-up (median 4.6, range 0-11 years) there were no deaths and only one re-intervention on a previously operated aortic segment, resulting in 92% reintervention-free survival at 5 years. CONCLUSIONS: In dedicated units, open surgical DTAA and TAAA repair in patients with CTD can be performed with a very low risk of death, severe complications and, late re-intervention. For CTD patients with reasonable risk, OSR should remain the first line of treatment.

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

Acute type A aortic dissection - a review.

Acute type A aortic dissection (ATAAD) is still one of the most challenging diseases that cardiac surgeons encounter. This review is based on the current literature and includes the results from the Nordic Consortium for Acute Type-A Aortic Dissection (NORCAAD) database. It covers different aspects of ATAAD and concentrates on the outcome of surgical repair. The diagnosis is occasionally delayed, and ATAAD is usually lethal if prompt repair is not performed. The dynamic nature of the disease, the variation in presentation and clinical course, and the urgency of treatment require significant attentiveness. Many surgical techniques and perfusion strategies of varying complexity have been described, ranging from simple interposition graft to total arch replacement with frozen elephant trunk and valve-sparing root reconstruction. Although more complex techniques may provide long-term benefit in selected patients, they require significant surgical expertise and experience. Short-term survival is first priority so an expedited operation that fits in with the surgeon's level of expertise is in most cases appropriate.

ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection.

Objectives. To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design. A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality. Results. There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups. Conclusions. In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.

Temporal and Morphological Patterns Predict Outcome of Endovascular Repair in Acute Complicated Type B Aortic Dissection.

OBJECTIVES: The aim was to analyse early and late outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR) for acute or subacute non-traumatic type B aortic dissection (TBAD), with the particular aims of identifying prognostic morphological predictors, and to assess the magnitude of the impact of the timing of TEVAR. METHODS: This was a retrospective, two centre, population based consecutive case series. The study group consisted of all the 53 patients undergoing TEVAR for complicated TBAD in Stockholm during the 12 year period 2004-2015. Demographic data, risk factors, operative, and outcome variables were registered and analysed. The CT scans were thoroughly retrospectively examined. RESULTS: Nearly half (24 patients; 45%) underwent TEVAR within 48 h of the onset of the initial symptoms, another 20 within 2 weeks, and nine in the subacute phase (15-90 days). The median age was 63 years (range 32-88) and 20 patients (38%) were women. The 30 day mortality was 17% (nine patients). Eight of these nine patients were treated within the first 48 h; urgent intervention (0-48 h) was associated with increased mortality (crude OR 14.0; 95% CI 1.6-122). All the nine patients had a false lumen area (FLA) at the level of the tracheal bifurcation exceeding 50% of the aortic cross sectional area at that segment, a finding significantly associated with increased mortality (p = .04), with a 25% 30 day mortality if the FLA > 50% (n = 36) at that segment, but 0% if the FLA was <50%. Overall the one year survival was 79% and five year survival 65%. CONCLUSIONS: All the early deaths demonstrated a FLA >50% of the total aortic cross sectional area at the level of the tracheal bifurcation. Patients needing urgent TEVAR had markedly worse outcome. The first finding may become an additional tool for future risk stratification.

The Nordic Consortium for Acute type A Aortic Dissection (NORCAAD): objectives and design.

OBJECTIVES: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) is a collaborative effort of Nordic cardiac surgery centers to study acute type A aortic dissection (ATAAD). Here, we outline the overall objectives and the design of NORCAAD. DESIGN: NORCAAD currently consists of eight centers in Denmark, Finland, Iceland and Sweden. Data was collected for patients undergoing surgery for ATAAD from 2005 to 2014. A total of 194 variables were retrospectively collected including demographics, past medical history, preoperative medications, symptoms at presentation, operative variables, complications, bleeding and blood transfusions, need for late reoperations, 30-day mortality and long-term survival. RESULTS: Information was gathered in the database for 1159 patients, of which 67.6% were male. The mean age was 61.5 ± 12.1 years. The mean follow-up was 3.1 ± 2.9 years with a total of 3535 patient years. CONCLUSIONS: NORCAAD provides a foundation for close collaboration between cardiac surgery centers in the Nordic countries. Substudies in progress include: short-term outcomes, long-term survival, time interval from diagnosis until operation, effects of surgical techniques, malperfusion syndrome, renal failure, bleeding and neurological complications on outcomes and the rate of late reoperations.

Open Repair of Aneurysms of the Thoracoabdominal Aorta.

Background Open surgical repair of aneurysms in the descending and thoracoabdominal aorta remains the dominating treatment of choice at many institutions worldwide. Patients treated with open repair most probably differ from endovascularly treated patients. With the present distribution of procedures performed for thoracoabdominal aortic aneurysms (TAAA), one cannot foresee any randomized controlled trial within the field. Several reports have, however, described similar midterm survival after open and endovascular repair. The objective of this report is to contribute the results from a contemporary series of open repair for TAAA at a dedicated aortic center. Methods All patients treated with open surgery for TAAA in the Stockholm County from 2007 to 2012 were included in the analysis. They were identified in the hospital administrative chart systems for operations and care. Results Twenty-eight patients were treated for TAAA, with a mean age of 61 (30-85) years, and 75% were male. Mean operative time was 573 (±190 minutes); left heart bypass was used in 75% of the operations and cardiopulmonary bypass in 25%. All patients had two to five visceral arteries reimplanted. During a 1-year follow-up period, one patient (3.6%) suffered permanent hemodialysis, one (3.6%) had a stroke, three (10.7%) had bowel ischemia, four (14.3%) had postoperative symptoms of spinal ischemia, and two of them (7.1%) had permanent paraplegia. No one died within 30 days, three patients (10.7%) died within 3 months, and 1-year mortality was 10.7%. Conclusion In an era of evolving endovascular alternatives to open surgery for TAAA, this contemporary series from an aortic center show excellent results that are comparable to most series of treated TAAA, both open and endovascular. It is highly probable that the case selection for the two treatment options should be made in centralized dedicated aortic centers with skills to handle all strategies of care.

Alternatives for arterial inflow in open surgical descending and thoracoabdominal aortic repair.

Surgical repair of the descending and thoracoabdominal aorta is regularly performed with the support of extracorporeal circulation. Femoral artery cannulation is the standard for arterial inflow, but presents, along with extremity hypoperfusion, the risk of embolization and malperfusion with retrograde aortic perfusion. There are alternatives for arterial inflow to avoid the drawbacks of the standard approach while accommodating different perfusion strategies. Ideally, with a broadened perfusion armamentarium, the choice of arterial inflow could be individualized to provide safe and efficient extracorporeal circulation.

Outcomes of aortic arch repair with extended (≥ 90 minutes) antegrade cerebral perfusion.

OBJECTIVES: To analyze outcomes with extended duration of antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest (HCA) for total arch repair (TAR). DESIGN: Retrospective study of consecutive patients undergoing TAR with HCA and ACP. Patients were divided into group A (ACP ≥ 90 min, n = 12) and group B (ACP < 90 min, n = 17) and compared regarding in-hospital mortality and neurological complications (primary outcome measures) and major complications, biochemical markers of organ damage, and blood product use (secondary outcome measures). Complications were analyzed according to standards of the International Aortic Arch Surgery Study Group. RESULTS: Overall in-hospital mortality was 4/29 (14%); 1/12 (8.3%) in group A versus 3/17 (18%) in group B, p = 0.62. No grade-V (lethal) neurological complication occurred, but five patients (all in group B) had grade-IV neurological complications: one general and two each focal and spinal neurological deficit (p = 0.047, overall). Prevalence of grade-II (temporary) general neurological deficit was 17% (group A) versus 27% (group B), p = 0.66. None of the patients suffered ≥ grade-IV respiratory or renal complications. Other complications, biochemical markers, and blood product usage were not significantly different. CONCLUSION: Outcomes in TAR with HCA and extended (≥ 90 min) three-vessel ACP were encouraging and could be contemplated with anticipated time-consuming TAR.

Incidence, presentation and outcome of acute aortic dissection: results from a population-based study.

OBJECTIVES: To describe the incidence of acute aortic dissection in a clearly defined population, to assess onset symptoms and admission biochemical marker levels and to analyse variables potentially associated to mortality. METHODS: Medical records and CT angiograms of all patients hospitalised for acute aortic dissection in the Stockholm County during the 5-year period 2012-2016 were reviewed. The patients were followed until date of death or until 31 December 2020. The annual incidence was determined. Associations between clinical and biochemical variables and 30-day mortality, respectively, were analysed using multivariable logistic regression models. RESULTS: A total of 344 patients were included. The mean annual incidence of acute aortic dissection was 4.1 per 100 000. Median age was 67 years (range 24-91) and 34% (n=118) were women. Type A dissection was predominant; 220 patients (64%) had type A and 124 (36%) had type B. Painless dissection was more common in type A than in type B (18% vs 15%, p=0.003). Type A dissection patients also more commonly had elevated plasma troponin T (44% vs 21%, p<0.001) and thrombocytopenia (26% vs 15%, p=0.010) than type B dissection patients on admission. Overall, 30-day mortality was 28% in type A and 11% in type B (p<0.001). Both painless dissection (OR 4.30, 95% CI 1.80 to 10.28, p=0.001) and elevated troponin T (OR 3.78, 95% CI 2.01 to 7.12, p<0.001), respectively, were associated with increased 30-day mortality in all acute aortic dissection patients. Thrombocytopenia was associated with elevated 30-day mortality only in patients with type A (OR 3.09, 95% CI 1.53 to 6.21, p=0.002). CONCLUSIONS: Nearly two-thirds of acute aortic dissection patients had type A. Levels of troponin T and platelets, respectively, paired with presence or absence of typical symptoms may become useful adjuncts in risk stratification of patients with acute aortic dissection.

Predictive machine learning models for ascending aortic dilatation in patients with bicuspid and tricuspid aortic valves undergoing cardiothoracic surgery: a prospective, single-centre and observational study.

OBJECTIVES: The objective of this study was to develop clinical classifiers aiming to identify prevalent ascending aortic dilatation in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). DESIGN AND SETTING: A prospective, single-centre and observational cohort. PARTICIPANTS: The study involved 543 BAV and 491 TAV patients with aortic valve disease and/or ascending aortic dilatation, excluding those with coronary artery disease, undergoing cardiothoracic surgery at the Karolinska University Hospital (Sweden). MAIN OUTCOME MEASURES: Predictors of high risk of ascending aortic dilatation (defined as ascending aorta with a diameter above 40 mm) were identified through the application of machine learning algorithms and classic logistic regression models. EXPOSURES: Comprehensive multidimensional data, including valve morphology, clinical information, family history of cardiovascular diseases, prevalent diseases, demographic details, lifestyle factors, and medication. RESULTS: BAV patients, with an average age of 60.4±12.4 years, showed a higher frequency of aortic dilatation (45.3%) compared with TAV patients, who had an average age of 70.4±9.1 years (28.9% dilatation, p <0.001). Aneurysm prediction models for TAV patients exhibited mean area under the receiver-operating-characteristic curve (AUC) values above 0.8, with the absence of aortic stenosis being the primary predictor, followed by diabetes and high-sensitivity C reactive protein. Conversely, prediction models for BAV patients resulted in AUC values between 0.5 and 0.55, indicating low usefulness for predicting aortic dilatation. Classification results remained consistent across all machine learning algorithms and classic logistic regression models. CONCLUSION AND RECOMMENDATION: Cardiovascular risk profiles appear to be more predictive of aortopathy in TAV patients than in patients with BAV. This adds evidence to the fact that BAV-associated and TAV-associated aortopathy involves different pathways to aneurysm formation and highlights the need for specific aneurysm preventions in these patients. Further, our results highlight that machine learning approaches do not outperform classical prediction methods in addressing complex interactions and non-linear relations between variables.

Mortality and reoperations in survivors operated on for acute type A aortic dissection and implications for catheter-based or hybrid interventions.

OBJECTIVE: This study investigated late outcomes (mortality, reoperations) and their associated predictors after operations for acute type A aortic dissection. The role catheter-based and hybrid interventions is discussed. METHODS: All hospital survivors operated on for acute type A aortic dissection from 1990 through 2009 were reviewed, with cross-sectional follow-up. Mortality (overall and aortic) and freedom from reoperations (proximal and distal) were estimated using actuarial methods. Preoperative, intraoperative, and postoperative variables (n = 44) associated with late outcomes were analyzed with univariable and multivariable (Cox) statistical methods. RESULTS: Of 360 operated-on patients, 291 hospital survivors (81%) were monitored for a median of 5.5 years (1864 patient-years). Total late mortality was 30% (n = 86), with estimated (standard error) survival of 82% (3%), 64% (4%), and 48% (6%) at 5, 10, and 15 years, respectively. Aortic events accounted for at least 27% (up to 42% including unknown causes) of late deaths. In Cox analysis, variables independently related (hazard ratios [95% confidence limits]) to late mortality were increased age (1.6 per 10 years [1.3, 2.0]), earlier operation (<2005; 2.3 [1.2, 4.6]), permanent neurologic damage (2.6 [1.6, 4.2]), and respiratory insufficiency (3.4 [1.8, 6.4]). Thirty-four patients underwent 46 reoperations, 21 on the proximal and 25 on the distal aorta, up to 19 years after the primary operation; respective in-hospital reoperative mortality was 14% and 12%. Estimated freedom (standard error) from aortic reoperation was 95% (2%), 87% (4%), and 61% (5%) at 5, 10, and 15 years, respectively. In multivariable Cox analysis (hazard ratios [95% confidence limits]), use of surgical adhesive at the primary operation (4.2 [1.6, 11]) and temporary neurologic damage (3.2l [1.2, 8.9]) were independently related to proximal reoperation, and DeBakey type I dissection (10.5 [1.4, 80]) was related to late distal reoperation. Catheter-based (endovascular, percutaneous) or hybrid procedures were not used in any patients but could have been used in up to 74% of reoperations, including in four of six of those that resulted in in-hospital death and putatively in 10 of 17 patients who sustained lethal aortic events without reoperation. CONCLUSIONS: Despite close follow-up, aortic-related death after a successful operation for acute type A aortic dissection is prevalent, and overall mortality remains substantial. Reoperations are not uncommon, may be indicated very late as well as repeatedly in the same patient, and are associated with a significant mortality. Increased use of applicable but seemingly under-used catheter-based or hybrid treatment approaches could benefit this growing patient population by offering repeat intervention to more patients and as substitute for reoperative open surgery in selected cases.

Impact of organ failure and major complications on outcome in acute Type A aortic dissection.

OBJECTIVES: Organ failure and major complications after operations for acute Type A aortic dissection impair outcomes. The objective was to analyze the prevalence of organ failure and major complications, their interrelationship and predictors, and their impact on early and late survival. DESIGN: All operative survivors 1990-2009 (n = 335) were retrospectively reviewed. Predictors of organ failure and major complications (bleeding, infection, renal or respiratory failure, neurological dysfunction, and multisystem organ failure) and their influence on in-hospital and long-term mortality were analyzed with multivariable statistical methods. RESULTS: Major complication(s) occurred in 153 patients (46%), most frequently bleeding and permanent neurological dysfunction (19% each). Increasing organ system failure index increased in-hospital mortality markedly: zero (2.9%), one (14%), two (33%), three or more (43%), p = 0.002. Reoperation for bleeding (odds ratio [95% confidence interval]) 2.6 [1.1-6.3], multisystem organ failure 4.3 [1.4-13], and permanent neurological dysfunction 14 [6.2-32] were related to in-hospital mortality. The latter two and respiratory failure also entailed increased long-term mortality. CONCLUSIONS: Organ failure and major complications were common and impacted negatively on both in-hospital and long-term survival. Strategies to avoid or treat organ failure and major complications should improve early and late survival after surgery for acute Type A aortic dissection.

Reoperation or Aortic Regurgitation Progression after Reimplantation of the Aortic Valve (David's Procedure) Using the Valsalva Graft.

BACKGROUND: This study aimed to assess predictors of a composite endpoint (reoperation for aortic valve [AV] failure or aortic regurgitation [AR] grade ≥ 2) after reimplantation of the aortic valve (RAV) using the Valsalva graft. METHODS: From 2012 to 2021, 112 patients underwent RAV in a single center. Clinical and echocardiographic data were collected retrospectively. Cox regression analysis was used to identify predictors of the composite endpoint. Kaplan-Meier methods were used for time-to-event analysis. RESULTS: Median (interquartile range) age was 52 years (44, 62). Nineteen patients (17%) were operated for acute Type A aortic dissection, and the remainder for aortic root aneurysm, 60 mm or larger in 12/112 (11%). Thirty-day mortality was 1/112 (1%). During follow-up, four patients (3.6%) were reoperated for AV failure, and another nine patients (8.1%) developed AR grade ≥ 2. Overall estimated freedom from reoperation or AR grade ≥ 2 was 87% (95% confidence interval: 76-93%) at 5 years. Significantly lower estimated 5-year freedom from the composite endpoint was found in cases with simultaneous aortic valve repair (AVr; 77 vs. 90%, p = 0.007) and nearly significant for large (≥ 6 cm) aortic root diameter (82 vs. 87%, p = 0.055). In Cox's analysis, aortic root diameter and simultaneous AVr were independent predictors for the composite endpoint. CONCLUSION: Outcomes (survival, reoperation, freedom from AR grade ≥ 2) with RAV were good up to 11-year follow-up. Larger aortic root diameter and simultaneous AVr were identified as predictors for reoperation or AR grade ≥ 2. Long-term follow-up remains necessary to confirm adequate AV function.

Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery.

BACKGROUND: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. METHODS: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). RESULTS: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). CONCLUSIONS: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.

SPP1/osteopontin: a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?

Degenerative ascending aortic aneurysm (AscAA) is a silent and potentially fatal disease characterized by excessive vascular inflammation and fibrosis. We aimed to characterize the cellular and molecular signature for the fibrotic type of endothelial mesenchymal transition (EndMT) that has previously been described in degenerative AscAA. Patients undergoing elective open-heart surgery for AscAA and/or aortic valve repair were recruited. Gene expression in the intima-media of the ascending aorta was measured in 22 patients with non-dilated and 24 with dilated aortas, and candidate genes were identified. Protein expression was assessed using immunohistochemistry. Interacting distal gene enhancer regions were identified using targeted chromosome conformation capture (HiCap) in untreated and LPS-treated THP1 cells, and the associated transcription factors were analyzed. Differential expression analysis identified SPP1 (osteopontin) as a key gene in the signature of fibrotic EndMT in patients with degenerative AscAA. The aortic intima-media expression of SPP1 correlated with the expression of inflammatory markers, the level of macrophage infiltration, and the aortic diameter. HiCap analysis, followed by transcription factor binding analysis, identified ETS1 as a potential regulator of SPP1 expression under inflammatory conditions. In conclusion, the present findings suggest that SPP1 may be involved in the development of the degenerative type of AscAA. KEY MESSAGES: In the original manuscript titled "SPP1/osteopontin, a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?" by David Freiholtz, Otto Bergman, Saliendra Pradhananga, Karin Lång, Flore-Anne Poujade, Carl Granath, Christian Olsson, Anders Franco-Cereceda, Pelin Sahlén, Per Eriksson, and Hanna M Björck, we present novel findings on regulatory factors on osteopontin (SPP1) expression in immune cells involved in degenerative ascending aortic aneurysms (AscAA). The central findings convey: SPP1 is a potential driver of the fibrotic endothelial-to-mesenchymal transition in AscAA. SPP1/osteopontin expression in AscAA is predominately by immune cells. ETS1 is a regulatory transcription factor of SPP1 expression in AscAA immune cells.

Bicuspid aortic valve aortopathy is characterized by embryonic epithelial to mesenchymal transition and endothelial instability.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation frequently associated with ascending aortic aneurysm (AscAA). Epithelial to mesenchymal transition (EMT) may play a role in BAV-associated AscAA. The aim of the study was to investigate the type of EMT associated with BAV aortopathy using patients with a tricuspid aortic valve (TAV) as a reference. The state of the endothelium was further evaluated. Aortic biopsies were taken from patients undergoing open-heart surgery. Aortic intima/media miRNA and gene expression was analyzed using Affymetrix human transcriptomic array. Histological staining assessed structure, localization, and protein expression. Migration/proliferation was assessed using ORIS migration assay. We show different EMT types associated with BAV and TAV AscAA. Specifically, in BAV-associated aortopathy, EMT genes related to endocardial cushion formation were enriched. Further, BAV vascular smooth muscle cells were less proliferative and migratory. In contrast, TAV aneurysmal aortas displayed a fibrotic EMT phenotype with medial degenerative insults. Further, non-dilated BAV aortas showed a lower miRNA-200c-associated endothelial basement membrane LAMC1 expression and lower CD31 expression, accompanied by increased endothelial permeability indicated by increased albumin infiltration. Embryonic EMT is a characteristic of BAV aortopathy, associated with endothelial instability and vascular permeability of the non-dilated aortic wall. KEY MESSAGES: Embryonic EMT is a feature of BAV-associated aortopathy. Endothelial integrity is compromised in BAV aortas prior to dilatation. Non-dilated BAV ascending aortas are more permeable than aortas of tricuspid aortic valve patients.