Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle

ObjectivesMost tissue-engineering approaches to restore injured heart muscle result in distortion of left ventricular geometry. In the present study we suggest seeding embryonic stem cells in a liquid matrix for myocardial restoration.MethodsUndifferentiated green fluorescent protein–labeled mouse embryonic stem cells (2 × 106) were seeded in Matrigel (B&D, Bedford, Mass). In a Lewis rat heterotopic heart transplant model an intramural left ventricular pouch was fashioned after ligation of the left anterior descending coronary artery. The liquid mixture (0.125 mL) was injected in the resulting infarcted area within the pouch and solidified within a few minutes after transplantation (37°C). Five recipient groups were formed: transplanted healthy hearts (group I), infarcted control hearts (group II), matrix recipients alone (group III), the study group that received matrix plus cells (group IV), and a group that received embryonic stem cells alone (group V). After echocardiography 2 weeks later, the hearts were harvested and stained for green fluorescent protein and cardiac muscle markers (connexin 43 and α-sarcomeric actin).ResultsThe graft formed a sustained structure within the injured area and prevented ventricular wall thinning. The inoculated cells remained viable and expressed connexin 43 and α-sarcomeric actin. Fractional shortening and regional contractility were better in animals that received bioartificial tissue grafts compared with control animals (infarcted, matrix only, and embryonic stem cells only: group I, 17.0% ± 3.5%; group II, 6.6% ± 2.1%; group III, 10.3% ± 2.2%; group IV, 14.5% ± 2.5%; and group V, 7.8% ± 1.8%).ConclusionsLiquid bioartificial tissue containing embryonic stem cells constitutes a powerful new approach to restoring injured heart muscle without distorting its geometry and structure

Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair

Objective: Fenestrated endovascular aneurysm repair (FEVAR) is a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as a treatment for failed EVAR. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine midterm outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. Methods:Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality rate, one year aneurysm sac dynamics (regression, stable, expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan–Meier methods, multivariable Cox regression analysis, chi square tests, and linear mixed effect models. Results: One hundred and ninety-six patients with FEVAR were identified, of whom 27% (n = 53) had had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p &lt; .001). There were no significant differences in mortality rate. FEVAR after EVAR was associated with a higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 – 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p &lt; .001). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p &lt; .001). Conclusion: There were high rates of sac expansion and a need for more secondary procedures in FEVAR after EVAR than primary FEVAR patients, although this did not affect midterm survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.</p

Nationwide Outcomes of Octogenarians Following Open or Endovascular Management After Ruptured Abdominal Aortic Aneurysms

PURPOSE: Octogenarians are known to have less-favorable outcomes following ruptured abdominal aortic aneurysm (rAAA) repair compared with their younger counterparts. Accurate information regarding perioperative outcomes following rAAA-repair is important to evaluate current treatment practice. The aim of this study was to evaluate perioperative outcomes of octogenarians and to identify factors associated with mortality and major complications after open surgical repair (OSR) or endovascular aneurysm repair (EVAR) of a rAAA using nationwide, real-world, contemporary data. METHODS: All patients that underwent EVAR or OSR of an infrarenal or juxtarenal rAAA between January 1, 2013, and December 31, 2018, were prospectively registered in the Dutch Surgical Aneurysm Audit (DSAA) and included in this study. The primary outcome was the comparison of perioperative outcomes of octogenarians versus non-octogenarians, including adjustment for confounders. Secondary outcomes were the identification of factors associated with mortality and major complications in octogenarians. RESULTS: The study included 2879 patients, of which 1146 were treated by EVAR (382 octogenarians, 33%) and 1733 were treated by OSR (410 octogenarians, 24%). Perioperative mortality of octogenarians following EVAR was 37.2% versus 14.8% in non-octogenarians (adjusted OR=2.9, 95% CI=2.8-3.0) and 50.0% versus 29.4% following OSR (adjusted OR=2.2, 95% CI=2.2-2.3). Major complication rates of octogenarians were 55.4% versus 31.8% in non-octogenarians following EVAR (OR=2.7, 95% CI=2.1-3.4), and 68% versus 49% following OSR (OR=2.2, 95% CI=1.8-2.8). Following EVAR, 30.6% of the octogenarians had an uncomplicated perioperative course (UPC) versus 49.5% in non-octogenarians (OR=0.5, 95% CI=0.4-0.6), while following OSR, UPC rates were 20.7% in octogenarians versus 32.6% in non-octogenarians (OR=0.5, 95% CI=0.4-0.7). Cardiac or pulmonary comorbidity and loss of consciousness were associated with mortality and major complications in octogenarians. Interestingly, female octogenarians had lower mortality rates following EVAR than male octogenarians (adjusted OR=0.7, 95% CI=0.6-0.8). CONCLUSION: Based on this nationwide study with real-world registry data, mortality rates of octogenarians following ruptured AAA-repair were high, especially after OSR. However, a substantial proportion of these octogenarians following OSR and EVAR had an uneventful recovery. Known preoperative factors do influence perioperative outcomes and reflect current treatment practice.publishersversionepub_ahead_of_prin

Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms:A Nationwide Prospective Cohort Study

Objective: The Dutch Surgical Aneurysm Audit (DSAA) initiative was established in 2013 to monitor and improve nationwide outcomes of aortic aneurysm surgery. The objective of this study was to examine whether outcomes of surgery for intact abdominal aortic aneurysms (iAAA) have improved over time.Methods: Patients who underwent primary repair of an iAAA by standard endovascular (EVAR) or open surgical repair (OSR) between 2014 and 2019 were selected from the DSAA for inclusion. The primary outcome was peri-operative mortality trend per year, stratified by OSR and EVAR. Secondary outcomes were trends per year in major complications, textbook outcome (TbO), and characteristics of treated patients. The trends per year were evaluated and reported in odds ratios per year.Results: In this study, 11 624 patients (74.8%) underwent EVAR and 3 908 patients (25.2%) underwent OSR. For EVAR, after adjustment for confounding factors, there was no improvement in peri-operative mortality (aOR [adjusted odds ratio] 1.06, 95% CI 0.94 – 1.20), while major complications decreased (2014: 10.1%, 2019: 7.0%; aOR 0.91, 95% CI 0.88 – 0.95) and the TbO rate increased (2014: 68.1%, 2019: 80.9%; aOR 1.13, 95% CI 1.10 – 1.16). For OSR, the peri-operative mortality decreased (2014: 6.1%, 2019: 4.6%; aOR 0.89, 95% CI 0.82 – 0.98), as well as major complications (2014: 28.6%, 2019: 23.3%; aOR 0.95, 95% CI 0.91 – 0.99). Furthermore, the proportion of TbO increased (2014: 49.1%, 2019: 58.3%; aOR 1.05, 95% CI 1.01 – 1.10). In both the EVAR and OSR group, the proportion of patients with cardiac comorbidity increased.Conclusion: Since the establishment of this nationwide quality improvement initiative (DSAA), all outcomes of iAAA repair following EVAR and OSR have improved, except for peri-operative mortality following EVAR which remained unchanged.</p

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair

Objective: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). Methods: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (&gt; 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan–Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. Results: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 – 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 – 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 – 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 – 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 – 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 – 285] cm 3 vs. 223 [95% CI 197 – 248] cm 3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. Conclusion: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.</p

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair

Objective: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). Methods: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (&gt; 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan–Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. Results: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 – 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 – 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 – 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 – 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 – 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 – 285] cm 3 vs. 223 [95% CI 197 – 248] cm 3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. Conclusion: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.</p

Male-Female Differences in Acute Type B Aortic Dissection

BACKGROUND: Acute type B aortic dissection is a cardiovascular emergency with considerable mortality and morbidity risk. Male-female differences have been observed in cardiovascular disease; however, literature on type B aortic dissection is scarce. METHODS AND RESULTS: A retrospective cohort study was conducted including all consecutive patients with acute type B aortic dissection between 2007 and 2017 in 4 tertiary hospitals using patient files and questionnaires for late morbidity. In total, 384 patients were included with a follow-up of 6.1 (range, 0.02-14.8) years, of which 41% (n=156) were female. Women presented at an older age than men (67 [interquartile range (IQR), 57-73] versus 62 [IQR, 52-71]; P=0.015). Prior abdominal aortic aneurysm (6% versus 15%; P=0.009), distally extending dissections (71 versus 85%; P=0.001), and clinical malperfusion (18% versus 32%; P=0.002) were less frequently observed in women. Absolute maximal descending aortic diameters were smaller in women (36 [IQR: 33-40] mm versus 39 [IQR, 36-43] mm; P&lt;0.001), while indexed for body surface area diameters were larger in women (20 [IQR, 18-23] mm/m2 versus 19 [IQR, 17-21] mm/m2). No male-female differences were found in treatment choice; however, indications for invasive treatment were different (P&lt;0.001). Early mortality rate was 9.6% in women and 11.8% in men (P=0.60). The 5-year survival was 83% (95% CI, 77-89) for women and 84% (95% CI, 79-89) for men (P=0.90). No male-female differences were observed in late (re)interventions. CONCLUSIONS: No male-female differences were found in management, early or late death, and morbidity in patients presenting with acute type B aortic dissection, despite distinct clinical profiles at presentation. More details on the impact of age and type of intervention are warranted in future studies.</p

Male-Female Differences in Acute Type B Aortic Dissection

BACKGROUND: Acute type B aortic dissection is a cardiovascular emergency with considerable mortality and morbidity risk. Male-female differences have been observed in cardiovascular disease; however, literature on type B aortic dissection is scarce. METHODS AND RESULTS: A retrospective cohort study was conducted including all consecutive patients with acute type B aortic dissection between 2007 and 2017 in 4 tertiary hospitals using patient files and questionnaires for late morbidity. In total, 384 patients were included with a follow-up of 6.1 (range, 0.02-14.8) years, of which 41% (n=156) were female. Women presented at an older age than men (67 [interquartile range (IQR), 57-73] versus 62 [IQR, 52-71]; P=0.015). Prior abdominal aortic aneurysm (6% versus 15%; P=0.009), distally extending dissections (71 versus 85%; P=0.001), and clinical malperfusion (18% versus 32%; P=0.002) were less frequently observed in women. Absolute maximal descending aortic diameters were smaller in women (36 [IQR: 33-40] mm versus 39 [IQR, 36-43] mm; P&lt;0.001), while indexed for body surface area diameters were larger in women (20 [IQR, 18-23] mm/m2 versus 19 [IQR, 17-21] mm/m2). No male-female differences were found in treatment choice; however, indications for invasive treatment were different (P&lt;0.001). Early mortality rate was 9.6% in women and 11.8% in men (P=0.60). The 5-year survival was 83% (95% CI, 77-89) for women and 84% (95% CI, 79-89) for men (P=0.90). No male-female differences were observed in late (re)interventions. CONCLUSIONS: No male-female differences were found in management, early or late death, and morbidity in patients presenting with acute type B aortic dissection, despite distinct clinical profiles at presentation. More details on the impact of age and type of intervention are warranted in future studies.</p