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.

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.

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.

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.

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.

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.

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.

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.

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair.

Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54-0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68-0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.

Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics.

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤-5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

High Prevalence of Thoracic Aortic Dilatation in Men with Previous Inguinal Hernia Repair.

BACKGROUND: Identifying a useful marker for thoracic aortic dilatation (TAD) could help improve informed clinical decisions, enhance diagnosis, and develop TAD screening programs. Inguinal hernia could be such a marker. This study tested the hypothesis that the thoracic aorta is larger and more often dilated in men with previous inguinal hernia repair versus nonhernia controls. METHODS: Four hundred men each with either previous inguinal hernia repair or cholecystectomy (controls) were identified to undergo chest computed tomography to measure the diameter of the thoracic aorta in the aortic root, ascending, isthmic, and descending aorta and to provide self-reported health data. Presence of TAD (root or ascending diameter > 45 mm; isthmic or descending diameter > 35 mm) and thoracic aortic diameters were compared between groups and associations explored using uni- and multivariable statistical methods. RESULTS: Complete data were obtained from 470/718 (65%) eligible participants. TAD prevalence was significantly higher in the inguinal hernia group: 21 (10%) versus 6 (2.4%), p = 0.001 for proximal TAD, 29 (13%) versus 21 (8.3%), p = 0.049 for distal TAD, and 50 (23%) versus 27 (11%), p < 0.001 for all aortic segments combined. In multivariable analysis, previous inguinal hernia repair was independently associated with dilatation of the proximal aorta (odds ratio 5.3, 95% confidence interval 1.8-15, p = 0.003). Contrarily, mean thoracic aortic diameters were similar (root and ascending aorta) or showed clinically irrelevant differences (isthmus and descending aorta). CONCLUSION: TAD, but not increased aortic diameters on average, was common and significantly more prevalent in men with previous inguinal hernia repair. Hernia could be a marker condition associated with increased prevalence of TAD. Ultimately, TAD screening could consider hernia as a possible selection criterion.

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.

Novel method for direct retransfusion reduces blood transfusions in descending and thoracoabdominal aneurysm repair.

BACKGROUND: Allogenic blood product usage is associated with worse outcomes in open repair of descending and thoracoabdominal aortic aneurysms. This pilot study evaluated the safety and efficacy of a novel modification of the left heart bypass (LHB) circuit to reduce intraoperative blood transfusions. METHODS: In modified LHB, pump suckers collected shed blood that was directly retransfused through a femoral vein cannula. In standard LHB, cellsavers were used to collect, wash, and retransfuse shed blood. Consecutive patients undergoing elective surgical descending or thoracoabdominal aneurysm repair using modified (N.=12) or standard (N.=21) LHB were compared. Intraoperative blood product use was the primary outcome. Hypotensive episodes, lactate levels, and adverse events (early mortality, spinal cord injury, renal and respiratory insufficiency) were secondary outcomes. RESULTS: Groups were comparable regarding pre- and intraoperative variables. No perfusion-related adverse events occurred. With modified LHB, intraoperative blood product use was significantly reduced: packed red blood cells by 60% from 10 to 4 units (P=0.002), fresh frozen plasma by 70% from 17 to 5 units (P<0.001) as well as retransfused cellsaver volume by 75%, from 4500 mL to 1110 mL (P<0.001). Hemodynamic instability occurred in 1 (8.3%) vs. 6 (29%), P=0.22 and overall lactate levels were significantly reduced (P=0.045) with modified LHB. Adverse events combined occurred in 1/12 vs. (P=0.022). CONCLUSIONS: The novel modified LHB with direct retransfusion was safe and associated with significantly reduced intraoperative blood product use, reduced lactate production and improved clinical outcomes as compared to standard LHB and could represent an important clinical improvement.

Acetylsalicylic Acid Is Associated With a Lower Prevalence of Ascending Aortic Aneurysm and a Decreased Aortic Expression of Cyclooxygenase 2.

Background Acetylsalicylic acid (ASA) therapy has been associated with a reduced prevalence and growth rate of abdominal as well as intracranial aneurysms, but the relationship between ASA and ascending aortic aneurysm formation remains largely unknown. The aim of the present study was to investigate whether ASA therapy is associated with a lower prevalence of ascending aortic aneurysm in a surgical cohort. Methods and Results One thousand seven hundred patients undergoing open-heart surgery for ascending aortic aneurysm and/or aortic valve disease were studied in this retrospective cross-sectional study. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥45 mm. Medications were self-reported by the patients in a systematic questionnaire. Cyclooxygenase gene expression was measured in the intima-media portion of the ascending aorta (n=117). In a multivariable analysis, ASA was associated with a reduced prevalence of ascending aortic aneurysm (relative risk, 0.68 [95% CI, 0.48-0.95], P=0.026) in patients with tricuspid aortic valves, but not in patients with bicuspid aortic valves (relative risk, 0.93 [95% CI, 0.64-1.34], P=0.687). Intima-media cyclooxygenase expression was positively correlated with ascending aortic dimensions (P<0.001 for cyclooxygenase-1 and P=0.05 for cyclooxygenase-2). In dilated, but not nondilated tricuspid aortic valve aortic specimens, ASA was associated with significantly lower cyclooxygenase-2 levels (P=0.034). Conclusions Our findings are consistent with the hypothesis that ASA treatment may attenuate ascending aortic aneurysmal growth, possibly via cyclooxygenase-2 inhibition in the ascending aortic wall and subsequent anti-inflammatory actions.

Sex Differences in Aortopathy and Valve Diseases Among Patients Undergoing Cardiac Surgical Procedure.

BACKGROUND: We aimed to study sex differences in aortopathy and valve disease among patients undergoing aortic valve replacement and/or surgical procedure for ascending aortic aneurysm and assess whether differences are specific for patients with bicuspid aortic valve (BAV) compared with patients with tricuspid aortic valve. METHODS: We used a single-center and observational cohort including 1045 patients undergoing elective open heart surgical procedure for aortic valve disease and/or ascending aortic aneurysm at the Karolinska Hospital (Stockholm, Sweden). RESULTS: Women (33.0%) were older than men (mean [SD]; 67.9 [11] years vs 62.5 [13] years for men; P < .001). No significant sex difference in prevalence of ascending aortic aneurysm was found according to absolute measures (P = .19); however, women had a greater dilation of the ascending aorta when normalized for body surface area (mean, 21.8 [SD, 6.3] mm/m2 vs 19.3 [SD, 4.4] mm/m2 for men; P < .001). Among the 560 patients with BAV, women had significantly more aortic stenosis (adjusted odds ratio, 2.23; 95% CI, 1.19-4.20; P = .013) and less aortic insufficiency (adjusted odds ratio, 0.42; 95% CI, 0.23-0.78; P < .01); whereas no sex difference was found among patients with tricuspid aortic valve. CONCLUSIONS: In this large study of patients undergoing cardiac surgical procedure, we found a greater degree of aortic dilation in women compared with men, suggesting a need for earlier monitoring of women. Moreover, women with BAV had a significantly higher prevalence of aortic stenosis compared with men. These results describe the aorta and valvular characteristics of patients by sex and provide guidance regarding which patients might benefit from closer surveillance.

Once after a full moon: acute type A aortic dissection and lunar phases.

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated. CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.

Metformin therapy is not associated with the lower prevalence of ascending aortic aneurysm in diabetic patients.

OBJECTIVES: Metformin therapy has previously been associated with reduced abdominal aortic aneurysm growth rate in diabetic patients and shown to suppress the formation and progression of abdominal aortic aneurysm in normoglycemic mice. Here, we investigated the association between Metformin treatment and prevalence of aneurysm in the ascending aorta (AscAA). METHODS: A total of 734 patients undergoing open-heart surgery for AscAA and/or aortic valve disease were studied. Diabetes status and medication use were self-reported by the patients in a systematic questionnaire. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥4.0 cm. High-sensitivity C-reactive protein levels were assessed as a measure of systemic inflammation. RESULTS: We could confirm the inverse association between diabetes and AscAA prevalence (16% vs 43.9%, for diabetic and non-diabetic patients, respectively; Odds ratio 0.243; 95% CI, 0.129-0.460, P < 0.001). Furthermore, in diabetic patients, Metformin treatment was associated with lower high-sensitivity C-reactive protein levels. There was, however, no difference in the prevalence of AscAA among diabetic patients with and without Metformin treatment (16% vs 16% for treated and non-treated patients, respectively; OR 1.039; 95% CI 0.26-4.19, P = 0.957). CONCLUSIONS: Our data do not support a protective effect of Metformin therapy in AscAA formation. SUBJ COLLECTION: 161, 173.

Outcome After Surgery for Acute Type A Aortic Dissection With or Without Primary Tear Resection.

BACKGROUND: The outcome in patients after surgery for acute type A aortic dissection without replacement of the part of the aorta containing the primary tear is undefined. METHODS: Data of 1122 patients who underwent surgery for acute type A aortic dissection in 8 Nordic centers from January 2005 to December 2014 were retrospectively analyzed. The patients with primary tear location unfound, unknown, not confirmed, or not recorded (n = 243, 21.7%) were excluded from the analysis. The patients were divided into 2 groups according to whether the aortic reconstruction encompassed the portion of the primary tear (tear resected [TR] group, n = 730) or not (tear not resected [TNR] group, n = 149). The restricted mean survival time ratios adjusted for patient characteristics and surgical details between the groups were calculated for all-cause mortality and aortic reoperation-free survival. The median follow-up time was 2.57 (interquartile range, 0.53-5.30) years. RESULTS: For the majority of the patients in the TR group, the primary tear was located in the ascending aorta (83.6%). The reconstruction encompassed both the aortic root and the aortic arch in 7.4% in the TR group as compared with 0.7% in the TNR patients (P < .001). There were no significant differences in all-cause mortality (adjusted restricted mean survival time ratio, 1.01; 95% confidence interval, 0.92-1.12; P = .799) or reoperation-free survival (adjusted restricted mean survival time ratio, 0.98; 95% confidence interval, 0.95-1.02; P = .436) between the TR and TNR groups. CONCLUSIONS: Primary tear resection alone does not determine the midterm outcome after surgery for acute type A aortic dissection.

Elevated Glucagon-like Peptide-1 and a Th2 Shift May Support Reduced Prevalence of Thoracic Aortic Aneurysm in Patients with Diabetes.

Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aimed to assess whether T2D alters the inflammatory profile/proteolytic activity, possible correlations to elevated fasting GLP-1 (F-GLP-1), and its relevance for TAA. F-GLP-1, pro-inflammatory T helper 1 (Th1) cytokines, Th2 cytokines, C-reactive protein, and matrix metalloproteinase-2 activity (MMP-2) were analyzed in surgical patients with aortic valve pathology with/without T2D and without T2D but with TAA. Patients with T2D displayed an increase in the relative systemic expression of interleukin 6 and tumor necrosis factor α and a clear trend towards reduced levels of interferon γ (IFNγ). In addition, a positive association between GLP-1 and the plasma interleukin 4 (IL-4)/IFNγ ratio was detected. TAA was associated with significantly lower plasma levels of the Th2 cytokines IL-4 and interleukin 5. Plasma MMP-2 activity did not differ between groups. We conclude that T2D involved a Th2 shift, which associates with elevated F-GLP-1 and may-considering Th1 bias in TAA-contribute to reduced prevalence of TAA in T2D.