Endovascular repair of thoracic aortic pseudoaneurysms and patch aneurysms

Pseudoaneurysms and patch aneurysms are life-threatening late complications after thoracoabdominal aortic aneurysm (TAAA) repair. We treated four patients who presented with a pseudoaneurysm or patch aneurysm involving the descending thoracic portion of a previously implanted TAAA graft. In each patient, stent grafts were placed within the existing graft to cover the aneurysm endoluminally. All patients recovered without major complications, and computed tomography performed after a mean follow-up of 51.5 ± 19.7 months showed that the repairs remained intact

Outcomes of concomitant aortic valve replacement and coronary artery bypass grafting at teaching hospitals versus nonteaching hospitals

ObjectiveHospitals with a high volume and academic status produce better patient outcomes than other hospitals after complex surgical procedures. Risk models show that concomitant aortic valve replacement and coronary artery bypass grafting pose a greater risk than isolated coronary artery bypass grafting or aortic valve replacement. We examined the relationship of hospital teaching status and the presence of a thoracic surgery residency program with aortic valve replacement/coronary artery bypass grafting outcomes.MethodsBy using the Nationwide Inpatient Sample database, we identified patients who underwent concomitant aortic valve replacement/coronary artery bypass grafting from 1998 to 2007 at nonteaching hospitals, teaching hospitals without a thoracic surgery residency program, and teaching hospitals with a thoracic surgery residency program. Multivariate analysis was performed to identify intergroup differences. Risk-adjusted multivariable logistic regression analysis was used to assess independent predictors of in-hospital mortality and complication rates.ResultsThe 3 groups of patients did not differ significantly in their baseline characteristics. Patients who underwent aortic valve replacement/coronary artery bypass grafting had higher overall risk-adjusted complication rates in nonteaching hospitals (odds ratio 1.58; 95% confidence interval, 1.39–1.80; P < .0001) and teaching hospitals without a thoracic surgery residency program (odds ratio 1.42; 95% confidence interval, 1.26–1.60; P < .0001) than in thoracic surgery residency program hospitals. However, no difference was observed in the adjusted mortality rate for nonteaching hospitals (odds ratio 0.95; 95% confidence interval, 0.87–1.04; P = .25) or teaching hospitals without a thoracic surgery residency program (odds ratio 1.00; 95% confidence interval, 0.92–1.08; P = .98) when compared with thoracic surgery residency program hospitals. Robust statistical models were used for analysis, with c-statistics of 0.98 (complications) and 0.82 (mortality).ConclusionPatients who require complex cardiac operations may have better outcomes when treated at teaching hospitals with a thoracic surgery residency program

HCMV infection attenuates hydrogen peroxide induced endothelial apoptosis – involvement of ERK pathway

AbstractHuman cytomegalovirus (HCMV) exerts anti-apoptotic effect during early stage of infection, which provides HCMV time for propagation. We investigated pathways mediating the resistance to H2O2-induced cell death – a self-defense mechanism to remove infected cells. We found that human aortic endothelial cells (HAECs) infected with VHL/E strain of HCMV during first 3 days were resistant to H2O2 (0–2mM) induced apoptosis. This anti-apoptotic effect may be mediated by the upregulation of Bcl-2, an anti-apoptotic protein through the activation pro-survival pathway extracellular signal regulated kinase (ERK). Through this mechanism, HCMV is able to propagate and causes endothelial dysfunction, hence vascular disease

Endovascular versus open repair of ruptured descending thoracic aortic aneurysms: A nationwide risk-adjusted study of 923 patients

ObjectiveRecent studies support the use of endovascular treatment for ruptured abdominal aortic aneurysms, but few studies have examined the use of thoracic endovascular aortic repair (TEVAR) for ruptured descending thoracic aortic aneurysm. We evaluated nationwide data regarding short-term outcomes of TEVAR and open aortic repair (OAR) for ruptured descending thoracic aortic aneurysm.MethodsFrom US Nationwide Inpatient Sample data, we identified 923 patients who underwent ruptured descending thoracic aortic aneurysm repair in 2006–2008 and who had no concomitant aortic disorders. Of these patients, 364 (39.4%) underwent TEVAR and 559 (60.6%) underwent OAR. Multivariable regression was used to assess the effect of TEVAR versus OAR after adjusting for potential confounding factors. Outcomes assessed were in-hospital mortality, complications, failure to rescue (defined as the mortality among patients in whom a complication develops), and disposition. Backward stepwise logistic regression was used to identify independent predictors of outcomes for each approach.ResultsPatients undergoing TEVAR were older (72 ± 12 years vs 65 ± 15 years; P < .001) and had a higher Deyo comorbidity index (4.19 ± 1.79 vs 3.14 ± 2.05; P < .001) than patients undergoing OAR. Unadjusted mortality was 23.4% (85/364) for TEVAR and 28.6% (160/559) for OAR. After risk adjustment, the odds of mortality, complications, and failure to rescue were similar for TEVAR and OAR (P > .1 for all), but patients undergoing TEVAR had a greater chance of routine discharge (odds ratio [OR] = 3.3; P < .001). An interaction was identified that linked hospital size and operative approach with risk of complications (P < .001). In smaller hospitals, TEVAR was associated with lower complication rates than OAR (OR = 0.21; P < .05). Regression analysis revealed that smaller hospital size predicted significantly higher rates of mortality (OR = 2.4; P < .05), complications (OR = 4.0; P < .005), and failure to rescue (OR = 51.12; P < .001) in those undergoing OAR but not in those undergoing TEVAR. Preexisting renal disorders substantially increased mortality risk (OR = 10.81; P < .001) and failure to rescue (OR = 309.54; P < .001) in patients undergoing TEVAR.ConclusionsNationwide data for ruptured descending thoracic aortic aneurysm reveal equivalent mortality, complication rates, and failure to rescue for TEVAR and OAR but more frequent routine discharge with TEVAR. Unlike OAR outcomes, TEVAR outcomes were not poorer in smaller hospitals, where TEVAR produced fewer complications than OAR. Therefore, TEVAR may be an ideal alternative to OAR for ruptured descending thoracic aortic aneurysm, particularly in small hospitals where expertise in OAR may be lacking and immediate transfer to a higher echelon of care may not be feasible

Valve-sparing and valve-replacing techniques for aortic root replacement in patients with Marfan syndrome: Analysis of early outcome

ObjectiveA prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients.MethodsWe assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%).ResultsNo in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6).ConclusionsThe analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches

Aortic Complications Associated With Pregnancy in Marfan Syndrome: The NHLBI National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139073/1/jah31693.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139073/2/jah31693_am.pd

Randomized comparison of cold blood and cold crystalloid renal perfusion for renal protection during thoracoabdominal aortic aneurysm repair

ObjectiveMore effective adjuncts are needed to reduce the incidence of acute renal injury after thoracoabdominal aortic aneurysm (TAAA) repair. The purpose of this randomized trial was to determine whether renal perfusion with cold blood provides better protection against renal ischemia than perfusion with cold crystalloid in patients undergoing TAAA repair with left heart bypass.MethodsOne hundred seventy-two patients were enrolled. Strict inclusion criteria were used, including planned Crawford extent II or III TAAA repair with left heart bypass. The patients were randomly assigned to receive intermittent renal perfusion with either 4°C lactated Ringer's solution (n = 86) or 4°C blood (n = 86). Renal complications within 10 days of operation were stratified by renal dysfunction score (RDS). Postoperative changes in the levels of five urinary biomarkers—retinol binding protein, α-1 microglobulin, microalbumin, N-acetyl-β-D-glucosaminidase, and intestinal alkaline phosphatase—were compared to assess potential differences in subclinical renal injury.ResultsAlthough total ischemic times were longer in the cold blood group, unprotected ischemic times were similar between the two groups. Twenty-seven patients in the cold blood group (31%) and 21 patients in the cold crystalloid group (24%) had peak RDS ≥2 (serum creatinine >50% above baseline; P = .4). There were no differences between the cold blood and cold crystalloid groups in the incidence of early death (7/86 [8%] vs 5/86 [6%], respectively; P = .8) or renal failure requiring hemodialysis (3/86 [3%] in both groups). Changes in renal biomarker levels were also similar in the two groups. Spinal cord deficits developed in 5 patients in the cold blood group (6%); there were no such deficits in the cold crystalloid group (P = .06).ConclusionCold renal perfusion during TAAA repair provides effective protection against renal injury. Using cold blood instead of cold crystalloid does not enhance renal protection

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan\u27s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan\u27s syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease

Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-β Signaling

The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-β signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-β receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-β signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-β pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-β signaling and lack of stimulus for SMC differentiation

Second Heart Field–Derived Cells Contribute to Angiotensin II–Mediated Ascending Aortopathies

BACKGROUND: The ascending aorta is a common location for aneurysm and dissection. This aortic region is populated by a mosaic of medial and adventitial cells that are embryonically derived from either the second heart field (SHF) or the cardiac neural crest. SHF-derived cells populate areas that coincide with the spatial specificity of thoracic aortopathies. The purpose of this study was to determine whether and how SHF-derived cells contribute to ascending aortopathies. METHODS: Ascending aortic pathologies were examined in patients with sporadic thoracic aortopathies and angiotensin II (AngII)–infused mice. Ascending aortas without overt pathology from AngII-infused mice were subjected to mass spectrometry– assisted proteomics and molecular features of SHF-derived cells were determined by single-cell transcriptomic analyses. Genetic deletion of either Lrp1 (low-density lipoprotein receptor–related protein 1) or Tgfbr2 (transforming growth factor–β receptor type 2) in SHF-derived cells was conducted to examine the effect of SHF-derived cells on vascular integrity. RESULTS: Pathologies in human ascending aortic aneurysmal tissues were predominant in outer medial layers and adventitia. This gradient was mimicked in mouse aortas after AngII infusion that was coincident with the distribution of SHF-derived cells. Proteomics indicated that brief AngII infusion before overt pathology occurred evoked downregulation of smooth muscle cell proteins and differential expression of extracellular matrix proteins, including several LRP1 ligands. LRP1 deletion in SHFderived cells augmented AngII-induced ascending aortic aneurysm and rupture. Single-cell transcriptomic analysis revealed that brief AngII infusion decreased Lrp1 and Tgfbr2 mRNA abundance in SHF-derived cells and induced a unique fibroblast population with low abundance of Tgfbr2 mRNA. SHF-specific Tgfbr2 deletion led to embryonic lethality at E12.5 with dilatation of the outflow tract and retroperitoneal hemorrhage. Integration of proteomic and single-cell transcriptomics results identified PAI1 (plasminogen activator inhibitor 1) as the most increased protein in SHF-derived smooth muscle cells and fibroblasts during AngII infusion. Immunostaining revealed a transmural gradient of PAI1 in both ascending aortas of AngIIinfused mice and human ascending aneurysmal aortas that mimicked the gradient of medial and adventitial pathologies. CONCLUSIONS: SHF-derived cells exert a critical role in maintaining vascular integrity through LRP1 and transforming growth factor–β signaling associated with increases of aortic PAI1