Thoracic Aortic Disease Research Articles

English

A bovine aortic arch is the most common variant of aortic arch branching in humans with a frequency ranging from 15 to 27% (1-2). It will be considered as a risk factor for aortopathy as anevrysm and dissection. Two cases were reported with association of bovine aortic arch and aortopathy. In both cases, the discovery of the anomaly of the aortic arch was fortuitous. A bovine aortic arch is frequent in patients with thoracic aortic disease than in the general population with a rapid evolution on the diameter of the aorta which expose patients to more complications such as anevrysm, rupture and dissection. It will be considered as a risk factor for aortopaty. Key words: Bovine aortic arch, aortopathy, common birth aortic arch.

Misdiagnosis of Thoracic Aortic Disease Occurs Commonly in Emergency Transfers

BackgroundAcute aortic syndromes (AASs) are prone to misdiagnosis by facilities with limited diagnostic experience. We assessed long-term trends in misdiagnosis among patients transferred to a tertiary care facility with presumed AASs. MethodsOur institutional transfer center database was queried for emergency transfers in patients with a diagnosis of AASs or thoracic aortic aneurysm between January 2008 and May 2018. There were 784 patients classified as emergency transfer for presumed AAS. Transferring diagnosis and actual diagnosis were compared through a review of physician notes and radiology reports from referring facilities and our center. ResultsMean age was 62 years, with 478 (61%) men. Differences in transferring diagnosis and actual diagnosis were identified in 89 patients (11.4%). Among misdiagnosed patients, the wrong classification of Stanford type A or type B dissections was identified among 24 patients (27%). No dissection was found in 23 patients (26%) with a referring diagnosis of aortic dissection. No signs of rupture were found in 18 patients (20%) transferred for contained/impending rupture. All misdiagnoses were secondary to misinterpretation of radiographic imaging, with motion artifacts in 14 (16%) and postsurgical changes in 22 (25%) being common sources of diagnostic error. Repeat scans were performed in 64 patients (72%) at our facility due to limited access to or suboptimal quality of outside imaging. ConclusionsAlthough AASs misdiagnosis rates appear to be improving from the prior decade, there are opportunities for improved physician awareness through campaigns such as “Think Aorta.” Centralized web-based imaging may prevent the costly hazards of unnecessary emergency transfer.

Abstract 12668: Mutant Smooth Muscle α-Actin Predisposes to Atherosclerosis and Augments Cholesterol-Driven Phenotypic Modulation of Vascular Smooth Muscle Cells

Heterozygous variants in ACTA2 (smooth muscle α-actin) predispose to thoracic aortic disease and early-onset coronary artery disease (CAD). Single cell RNA sequencing (scRNA-Seq) identified phenotypically modulated SMCs (mSMCs; de-differentiated SMCs with upregulation of macrophage and fibroblast markers) that appear with atherosclerotic plaque formation in the aortas of Apoe -/- mice. Importantly, this transition is dependent on Kruppel-like factor 4 (Klf4). We previously demonstrated that SMCs exposed to free cholesterol complexed to methyl-β-cyclodextrin (MBD-Chol) in vitro activate unfolded protein response (UPR) pathways upstream of Klf4 and assume a mSMC phenotype. Blocking the UPR Perk pathway abolishes modulation. We sought to determine how ACTA2 p.Arg149Cys causes early-onset CAD. Acta2 R149C/+ mice were generated using CRISPR/Cas9. Acta2 R149C/+ mice were crossed into Apoe -/- mice and fed a high fat diet for 3 months. Oil Red O staining and en face aortic analysis showed that Acta2 R149C/+ Apoe -/- aortas developed significantly more plaques than similarly treated Apoe -/- mice (p<0.01) with no difference in plasma lipid levels ( Fig. 1A ). ScRNA-Seq of the root and ascending aorta showed no novel SMC cluster, however mSMC clusters demonstrated increased expression of UPR markers and Klf4 in the Acta2 R149C/+ Apoe -/- aortas compared to Apoe -/- aortas. Strikingly, Acta2 R149C/+ SMCs upregulate modulation markers at much lower levels of cholesterol than WT SMCs due to activation of the UPR Perk-Klf4 by misfolded mutant SM α-actin ( Fig. 1B ). Importantly, blocking Perk abolishes the augmented phenotypic modulation in Acta2 R149C/+ SMCs. These findings identify a novel pathway driving atherosclerosis independent of lipid metabolism and confirm a key role of SMCs in atherosclerotic plaque formation.

Abstract 12566: Aortic Smooth Muscle Cell Focal Adhesion Kinase (FAK) Activation is Prominently Associated With Acute Aortic Dissections in Patients and Mouse Models and Loss of FAK Signaling Augments Dissections in Mice

Introduction: Genetic variants predisposing to thoracic aortic disease disrupt proteins either in the extracellular matrix (ECM) or the smooth muscle cell (SMC) contractile unit, and focal adhesions (FAs) are molecular bridges between these aortic wall components. We sought to identify molecular triggers for acute aortic dissection (AAD) in a mouse model with AAD induced by β-aminopropionitrile (BAPN) and patients with type A AAD. Methods: At postnatal day 21 (P21), C57BL/6J mice were exposed to BAPN in drinking water (0.5%) and proximal aortas were harvested for single-cell RNA sequencing (scRNA-seq), proteomics assays and transmission electron microscopic (TEM) analysis at P35. Ascending aortic scRNA-seq assays were performed on AAD patients (n=3) and age-matched, cardiac transplantation donors (n=3). Results: In the BAPN mice, ruptured AAD-deaths started at P36, and 54% of mice died by P49, despite a significant decrease of BP (111/79 to 95/66 mmHg, p<0.0001). ScRNA-seq and KEGG pathway analysis identified increased FA signaling as the top altered pathway in the BAPN-treated SMC clusters. Similarly, FA signaling was identified as a top upregulated pathway in SMCs from patients’ aortas. Western blots confirmed increased level of FAK phosphorylation in BAPN-treated aortas. Proteomics analysis revealed a FAK-interacting protein, cortactin, and apoptotic proteins, annexin A1, A3 and A5 (p<0.01), as the top proteins increased with BAPN treatment, which was consistent with increased TUNEL signal in BAPN-treated aortas (p<0.01). TEM analysis identified collagen deposition between SMCs and elastic fibers and loss of elastic extensions in BAPN-treated aortic media. Importantly, administration of a FAK inhibitor, PF-573228, starting at P30 in BAPN-treated mice significantly increased AAD-deaths (starting at P35 and all mice died by P48) when compared to BAPN-only treated mice (p<0.0001). Conclusions: FA signaling is the major pathway activated in SMCs in mouse pre-dissection aortas and human dissected aortas, thus implicating disruption of SMC-ECM interactions in AADs. Disruption of FAK signaling augments AADs, suggesting that maintenance of FA signaling delays AADs in the ECM-compromised, BAPN-treated aortas.

Identifying risk factors for early neurological outcomes following thoracic endovascular aortic repair using the SUMMIT database.

The aim of this study was to assess risk factors for early neurological complications following thoracic endovascular aortic repair (TEVAR) for multiple thoracic aortic diseases using an aggregated dataset. The Study to Assess Outcomes After Endovascular Repair for Multiple Throacic Aortic Disease dataset included data from 6 studies evaluating Zenith thoracic endografts. Post hoc analysis identified early (30-day) neurological complications by TEVAR indication and corresponding risk factors. The study included 594 TEVAR patients (67% male; mean age 66 ± 15 years) with thoracic aortic aneurysm (n = 329), ulcer (n = 56), acute (n = 126) or non-acute (n = 33) type B aortic dissection (TBAD) or blunt injury (n = 50). Overall early stroke rate was 3.5% (n = 21). Overall early paraplegia and paraparesis rates were 1.3% (n = 8) and 2.5% (n = 15), respectively. Multivariable analysis identified acute TBAD [versus others, odds ratio (OR) = 3.47, 95% confidence internal (CI): 1.41-8.52) and longer procedural time (OR = 1.33, CI: 1.02-1.73) as early stroke risk factors. Risk factors for paraplegia or paraparesis included more endografts deployed (OR = 2.43, CI: 1.30-4.55), older age (OR = 1.05, CI: 1.01-1.10) and higher preoperative serum creatinine (OR = 1.31, CI: 1.05-1.64). Endografts landing proximal to the left subclavian artery (LSA) increased stroke rate (versus distal to the LSA; 6.8% vs 2.3%, P = 0.014). Intraoperative LSA revascularization was performed in 20.9% of patients with endografts proximal to the LSA; revascularization did not significantly alter stroke rate (8.1% with revascularization vs 6.4% without, P = 0.72). Acute TBAD and prolonged procedure time increased early stroke risk, while more endografts placed, age and preoperative renal impairment increased early paraplegia or paraparesis risk. For acute TBAD, endograft placement proximal to the LSA, but not LSA patency, increased stroke risk.

Sex Differences in Proximal Thoracic Aortic Disease Pathology: A Call to Action

Abstract Introduction/Objective Sex disparity is reported across all forms of cardiovascular diseases. Only few studies have focused on sex differences in thoracic aortic disease pathology. We aim to identify and understand sex differences in this patient group to bridge the knowledge gap and improve clinicopathologic outcomes. Methods/Case Report This is a retrospective analysis of 83 proximal thoracic aortic aneurysm and dissection (TAAD) cases treated at a single quaternary care center in 2019. Chart review was done for demographics. Consensus criteria (Stone JR et al. Cardiovasc Pathol 2015; 24:267-78; Halushka MK et al. Cardiovasc Pathol 2016; 25:247-57) and a scoring system (Waters KM et al. Cardiovasc Pathol 2017; 30:6-11) were used for pathology reporting. Clinical correlation was also made. Pearson’s chi-square test was used for statistical analysis. Results (if a Case Study enter NA) 83 patients (61 male and 22 female) were retrieved. Overall thoracic aortopathy was higher among males, accounting for 73.4% of individuals with TAAD. In a subgroup analysis, there was no sex difference in dissection, aortic root involvement, and bicuspid aortic valve (p>0.05). Genetic aortopathy was more prevalent in females than males (27.2% vs 9.8%, p=0.04) alongside early age at first aortic event (median age: 31y vs 52y). Histopathologically, females had frequent translamellar mucoid extracellular matrix accumulation (45.4% vs 22.9%, p=0.04), extensive (54.5% vs 27.8%, p=0.02) and severe (59% vs 34.4%, p=0.04) elastic fiber fragmentation, higher band like (9% vs 6.5%, p>0.05) plus extensive (13.6% vs 4.9%, p>0.05) smooth muscle nuclei loss, and extensive (13.6% vs 1.6%, p=0.01) plus dense (4.5% vs 1.6%, p>0.05) laminar medial collapse than males. Conclusion In our patient population, females have a lower prevalence of thoracic aortic disease treated with open repair. However, those who develop TAAD harbor a greater burden of wall pathology and probable worse outcomes. We recommend sex-based analysis of all research on thoracic aortic diseases.

Effect of intracordal injection under local anesthesia on vital signs in high-risk patients

ObjectiveIntracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. MethodsA retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. ResultsThe average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. ConclusionIntracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.

Utility of familial screening in non-syndromic thoracic aortic disease

Abstract Background Non-syndromic heritable thoracic aortic disease (nsHTAD) is an autosomal dominant disorder with high mortality rate if undetected. Familial evaluation could be useful to identify high-risk patients early. Purpose To assess the yield of clinical and genetic screening in a cohort of patients with suspected nsHTAD. Methods We collected clinical and genetic data about patients with suspected nsHTAD treated in a specialized clinic. Bicuspid aortic valve cases were excluded. Genetic study was performed with next-generation-sequencing, including at least 30 related genes. All first degree relatives were offered evaluation according to current guidelines. Results Twenty-five index cases were analysed (mean age: 48.3 years, male: 64%). Sixteen patients (64%) presented with acute aortic dissection (postmortem diagnosis was performed in 6 cases with sudden cardiac death). Hypertension was reported in 13 cases (52%) and 8 patients (32%) had smoking history. Family history of aortic aneurysm or dissection was identified in 13 cases (52%). Eighty-three first-degree relatives were evaluated. Clinically affected family members were detected in 10 families (40%). Genetic cause of the disease was identified in 6 families (24%). Table 1 describes main characteristics of index cases with pathogenic variants. Combined clinical and genetic screening was positive in 12 families (48%) and identified 24 relatives (29%) with aortic dilatation or carrier status for the disease. Conclusions The combination of clinical and genetic screening in suspected nsHTAD is a useful tool for early detection of the disease in family members at risk and for the prevention of future complications. Funding Acknowledgement Type of funding sources: None. Table 1

18F-Sodium fluoride positron emission tomography, aortic disease activity and ischaemic stroke risk

Abstract Background Arterial 18F-sodium fluoride (18F-NaF) activity on positron emission tomography (PET) is a marker of active microcalcification and atherosclerosis. Coronary 18F-NaF activity (CMA) predicts coronary artery disease progression and subsequent myocardial infarction. Objective To investigate whether aortic 18F-NaF activity (AMA) predicts thoracic aortic atherosclerotic disease progression and subsequent ischaemic stroke or myocardial infarction in patients with established cardiovascular disease. Methods In a post-hoc observational cohort study, we evaluated AMA and CMA in patients with stable coronary artery disease (n=239) or aortic stenosis (n=158) who had underwent thoracic 18F-NaF PET and computed tomography (CT). We assessed the associations between AMA or CMA and progression of calcified atherosclerotic plaque in both thoracic aortic and coronary territories on follow up CT, as well as subsequent ischaemic stroke or myocardial infarction. Results In 141 and 231 patients with repeat aortic and coronary CT imaging respectively at 12.7±2.7 months, AMA correlated with log progression of thoracic aortic calcium scores (r=0.21, p=0.011), volume (r=0.29, p<0.01) and mass (r=0.29, P<0.01) as well as log coronary calcium score progression (r=0.21, p=0.03). CMA correlated with log coronary (r=0.42, p<0.01), but not log aortic (p>0.80) calcium score progression. In 397 patients, 16 had an ischaemic stroke and 25 had a myocardial infarction after 4.7±1.6 years. After adjusting for clinical risk factors, CMA and calcium scoring, AMA was associated with stroke (hazard ratio, 1.71 [95% confidence interval 1.00–2.90], p=0.048]). AMA was superior to clinical risk and calcium scores in identifying patients with stroke (c-statistic 0.76 versus 0.58 versus 0.63 respectively, p<0.05). Survival analysis demonstrated that AMA was associated with ischaemic stroke (p<0.001) but not myocardial infarction (p=0.45), whereas CMA was associated with myocardial infarction (p<0.001) but not stroke (p=0.39). Conclusions In patients with established cardiovascular disease, AMA is associated with progression of aortic atherosclerosis and future ischaemic stroke. Arterial 18F-NaF identifies localised areas of atherosclerotic disease activity that relate to regional atherothrombotic events. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): British Heart Foundation AMA, disease progression and outcomesVariables associated with stroke

Do morphological, haemodynamic and biomechanical parameters relate to aortic growth rate in chronic type B aortic dissection? A 4D flow CMR study

Abstract Background Aortic dissection (AD) is the most devastating complication of thoracic aortic disease (1). In the chronic phase, yearly clinical and imaging follow-up of the maximum aortic diameter is recommended, since indication for thoracic endovascular aortic repair or surgery is suggested by guidelines in case of thoracic aortic enlargement or false lumen (FL) aneurysms (2). Most of the reported parameters related adverse events in chronic AD are focused on morphological variables (3) and not on the haemodynamics and biomechanics of the FL. Purpose To evaluate the relationship between aortic growth rate and anatomical variables, flow patterns and aortic stiffness in patients with chronic type B AD. Methods Forty-one patients with chronic type B aortic dissection, no connective tissue disorders and with an imaging follow-up including two computed tomography angiograms (CTA) acquired at least 3 years apart underwent contrast-enhanced 4D-flow CMR and MR angiography (MRA). The FL volume was segmented from MRA, and velocity data inside the 3D volume of the FL was extracted from 4D-flow CMR and used for parameter quantification. Retrograde systolic and diastolic flow, wall shear stress (WSS) and in-plane rotational flow (IRF) were calculated at 8 equidistant planes in the distal descending aorta (DAo), from the pulmonary bifurcation to the diaphragmatic level, and averaged values were used [4]. Aortic stiffness in the FL was assessed in terms of pulse wave velocity (PWV), which was calculated from the third supraortic trunk to the diaphragmatic level on 4D-flow CMR [5]. The percentage of thrombus in the FL was calculated as the ratio of thrombus and FL volumes on MRA. Dominant entry tear area was quantified on the baseline CTA (Figure 1). Aortic growth rate (GR) was defined as the difference between final and baseline aortic diameters as measured on CTA divided by follow-up duration. Results Anatomical, haemodynamic and biomechanical parameters are shown in Table. Twenty-five patients have repaired type A AD with residual entry tear and 16 have type B AD. Mean follow-up duration was of 4.9±2.7 years. In bivariate analysis, WSS, IRF and PWV were positively related to GR, whereas dominant entry tear area and percentage of thrombus in the FL showed a positive tendency with GR (Table) (Figure). In multivariate analysis IRF, PWV, dominant entry tear area and thrombus in the FL were positively and independently associated with GR (Table). Retrograde systolic and diastolic flow were not related to GR while WSS tended to statistical significance. Conclusions In-plane rotational flow, regional aortic stiffness, dominant entry tear area and percentage of thrombus in the false lumen are positively and independently related to aortic growth rate in patients with chronic type B aortic dissection. Further prospective studies are needed to confirm if the assessment of these parameters may help to identify patients at higher risk of adverse clinical events. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Mitral annular disjunction in patients with syndromic hereditary aorthopaties

Abstract Background Mitral annular disjunction (MAD) is a structural abnormality of the mitral annular fibrosus characterized by a separation between the atrial wall-mitral valve junction, and the left ventricular attachment (1). It has been associated with mitral valve prolapse (MVP) (2) but also, with arrhythmias and sudden cardiac death (SCD) (3). There is no evidence of its prevalence and clinical significance in patients with syndromic hereditary aortopathies. Purpose To evaluate the prevalence of MAD, PMV, and the combination of both in patients with syndromic hereditary thoracic aortic disease (HTAD) including Marfan (MFS), Loeys-Dietz (LDS) and vascular Ehlers-Danlos syndromes (vEDS), and its relationship with arrhythmias, SCD, mitral regurgitation (MR) severity and the need for mitral surgery at the follow-up. Methods Adult patients with syndromic HTAD seen at our specialized unit were retrospectively included. The presence of MAD, MVP, and significant MR at first echocardiogram were evaluated. Electronic medical records were reviewed to register the occurrence of arrhythmic events and the need of mitral surgery. Last echocardiogram available was also assessed to evaluate MR progression. Results A total of 295 patients were included (235 MFS, 42 LDS and 18 vEDS). Mean age at baseline was 39.0±14.4 and 52.9% were female. MAD was present in 87 (37.0%) of MFS, 6 (14.3%) of LDS and was not present in vEDS (p<0.001). MVP was found in 105 (44.7%) of MFS, 6 (14.3%) of LDS and 0 in vEDS (p<0.001). In MFS, the presence of MAD was significantly associated with MVP (p≤0.001) (Table 1). However, 14 (6.0%) of patients had isolated MAD (Table 2). At baseline, significant MR was observed in 18 (24.7%) of patients with concurrent MAD and MVP and was not present in patients with isolated MAD (Table 2). MVP (OR 16.85 IC 4.43 – 64.07) but not MAD (p=0.607), was associated with significant MR in the multivariate analysis. A second echocardiogram was available in 220 patients at ≥1 year (mean 4.1±1.4 years). Overall, 25 (11.4%) presented significant progression of MR, 0 in the isolated MAD group, 13 (19.4%) in the MAD/MVP group and 6 (20.0%) of the isolated MVP (p=0.007). After a mean clinical follow-up of 7.5±3.2 years, 10 patients required mitral surgery (6 prosthesis, 4 valvuloplasty), 22 (9.4%) presented atrial fibrillation, flutter or supraventricular tachycardia (SVT), and 2 (0.9%) SCD. After adjustment for the presence of MVP and time of follow-up, MAD was not associated with progression of MR (p=0.529) need for mitral surgery (p=0.096), atrial fibrillation-flutter or SVT (p=0.510) nor SCD. (p=0.997). Conclusions The prevalence of MAD in syndromic HTAD is high, especially in Marfan syndrome, and absent in vEDS. In this retrospective observational study, the presence of MAD in Marfan was not associated with mitral regurgitation evolution or arrhythmic events. Funding Acknowledgement Type of funding sources: None. Characteristics of MFS patientsPresence of significant MR by groups.

Aortic Z-scores in paediatric patients with marfan syndrome and other hereditary thoracic aortic diseases

Abstract Introduction Marfan syndrome (MFS) and other hereditary thoracic aortic diseases (HTAD) are characterized by dilatation of the aorta caused by mutations in the FBN1-gene and other aortic genes. To prevent aortic dissection or rupture, patients are prophylactically treated by aortic surgery. Different z-scores of the aortic root are used for diagnosis and monitoring in paediatric patients. Purpose What are the differences between the various aortic Z-scores in their use for monitoring, assessing the severity of the aortic disease, and establishing the indication for surgery in this age group? Methods We retrospectively analyzed the diameters of aortic roots measured by echocardiography in 180 children and young adults (1 month to 25 years) with MFS and other HTADs presenting at our specialized outpatient clinic between January 2010 and August 2019. Thirteen patients underwent surgery during this period and 121 were monitored for a duration of one up to nine years. Five aortic z-scores were compared: Pettersen, Gautier, Cantinotti, Lopez, Boston. For evaluation of the severity of dilatation and indication for surgery, we used the last value before operation or the last follow-up value. For monitoring, we used the difference between the first and the last value. For comparison of the z-scores, values of the sinuses of Valsalva were analyzed. We investigated theoretic backgrounds and reference groups of each z-score. Results The z-score values differ significantly (p<0,001) for each score. The medians reach from 2.06 to 3.45, in operated patients 4.90 to 8.52, non-operated patients 1.86 to 3.31 (p<0,001). 93 aortic diameters to 136 were classified as dilatated (z-score ≥2). There were significant differences of almost all z-scores in the comparison with one another. During follow-up, the increase of the median z-score ranged from 0.11 to 0.24, in operated patients from 0.73 to 1.93, in non-operated patients from 0.02 to 0.21, respectively. The median monitoring time was 4.14 years and 2.93 years, for patients monitored for more than one year and all patients, respectively. In the operated subgroup, a weak correlation showed that the longer the monitoring time and the closer the surgery arrived, the faster the z-scores rose. Lopez, Boston and Cantinotti have higher values and label a value quicker than dilatated, but also reveal the severity of dilatation and the potential necessity of surgery. Conclusions Our data show that the various z-scores differ significantly. No z-score was superior regarding above-mentioned aspects, their differences in monitoring were small. However, it seems important to consistently use one same z-score. Expectedly, z-score values of each score were higher in the operated subgroup than in patients without surgery. However, there is no z-score value that determines a clear-cut indication for surgery. Funding Acknowledgement Type of funding sources: None.

Arrhythmia and cardiomyopathy in Heritable Thoracic Aortic Disease: an international retrospective cohort study

Abstract Background Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and related heritable thoracic aortic diseases (HTAD) are well-known for their aortic complications. Myocardial dysfunction and arrhythmia are less known in this setting but have been increasingly reported as additional causes of morbidity and mortality. Related to the rarity of the disorders, data on the prevalence of these features and clinical characteristics of the patients are difficult to obtain, calling for a multicentre initiative. Purpose To study the prevalence of myocardial dysfunction and arrhythmia in patients with HTAD and describe their clinical and genetic profile. Methods Nine centres from seven countries participated in this multicentre retrospective study. Medical records of patients 12 years or older carrying a (likely) pathogenic variant in the FBN1 gene, LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) or ACTA2 gene were screened. Patients presenting myocardial dysfunction and/or arrhythmia were identified, and clinical and genetic data were collected. Myocardial dysfunction included (a)symptomatic reduced ejection fraction (EF <50% – HFrEF) or symptomatic preserved EF (HFpEF), as documented in the patient charts. Arrhythmias included atrial fibrillation or flutter (AF/AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and (aborted) sudden cardiac death (SCD) (presumed arrhythmogenic). Results In total, 3219 patients with HTAD were screened: 2761 with a variant in FBN1, 385 with a variant in one of the LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) and 73 carrying a variant in ACTA2. Myocardial dysfunction and arrhythmia were not reported in patients carrying an ACTA2 variant. Myocardial dysfunction was observed in patients with a variant in FBN1 and the LDS genes, without significant differences in prevalence (2.3% vs. 1.8%, p=0.563). Patients with a variant in the LDS genes presenting myocardial dysfunction were younger than patients carrying a variant in FBN1 (25±11 years vs. 39±17 years, p=0.034). The prevalence of VT/VF/SCD was similar in patients with a variant in one of the LDS genes compared to those with a variant in FBN1 (1.6% vs. 0.8%, p=0.132) and there was no difference in age at time of event (26±13 years vs. 33±14 years, p=0.289). Among patients with a variant in the LDS genes, the prevalence of VT/VF/SCD was highest in patients carrying a variant in the TGFBR2 gene and was significantly higher compared to patients with a variant in FBN1 (3.4% vs. 0.8%, p=0.017). In contrast, AF/AFL was significantly more often reported in patients with a variant in FBN1 compared to those with a variant in one of the LDS genes (1.7% vs. 0.3%, p=0.033). Conclusions Myocardial dysfunction and arrhythmia are rare features in patients with HTAD. They occur predominantly in patients with a variant in FBN1 and LDS genes, but were not reported in patients carrying a variant in the ACTA2 gene. Further analysis to identify other contributing factors is necessary. Funding Acknowledgement Type of funding sources: None. Figure 1

Intramural Haematoma Type B: Many Questions and Some Answers

Intramural haematoma (IMH) is included in acute aortic syndromes (AAS), together with aortic dissection (AD) and penetrating aortic ulcer (PAU). Its incidence is reported to be 5% – 20% of all AAS. Most of the recommendations on how to manage IMH stem from studies on AD or patients with mixed AAS pathologies, and little is known about the indications for treatment. In particular, the 2017 European Society for Vascular Surgery guidelines on the management of thoracic aorta disease recommend that endovascular repair should be considered only for complicated type B IMH (class IIa recommendation).

1655 Thoracic Aortic Aneurysmal Disease: Timing and Outcome of Surgery

Abstract Aim A thoracic aortic aneurysm (TAA) is a pathological dilatation of the thoracic aorta. There is significant morbidity associated with a dilated aorta including mortality. Open thoracic surgery is the mainstay of management for proximal lesions, offering definitive treatment. We aim to evaluate the outcomes of patients operated on for TAA and consider high risk associations for mortality. Method Data was retrospectively collected from 234 patients that underwent elective open thoracic surgery at UHS for TAA disease, between 2015 and 2019. Demographics, clinical factors, surgical details, as well as outcome measures were gathered. Results There were 166 males (71%) and 68 females (29%), with a mean age of 66 years. We found that 105 operations involved the aortic root, 171 the ascending aorta, 20 the aortic arch and 12 the descending aorta. 30 day mortality was 5.13%. Female patients that underwent aortic root surgery (P = 0.05), as well as those with prosthetic aortic valves (P = 0.01)and post-operative complications were associated with a significantly higher mortality. Conclusions A number of factors are associated with morbidity and mortality in this high-risk Surgery. These should be considered when discussing risks of intervention with patients.

Resistance of Acta2R149C/+ mice to aortic disease is associated with defective release of mutant smooth muscle α-actin from the chaperonin-containing TCP1 folding complex

Pathogenic variants of the gene for smooth muscle α-actin (ACTA2), which encodes smooth muscle (SM) α-actin, predispose to heritable thoracic aortic disease. The ACTA2 variant p.Arg149Cys (R149C) is the most common alteration; however, only 60% of carriers have a dissection or undergo repair of an aneurysm by 70 years of age. A mouse model of ACTA2 p.Arg149Cys was generated using CRISPR/Cas9 technology to determine the etiology of reduced penetrance. Acta2R149C/+ mice had significantly decreased aortic contraction compared with WT mice but did not form aortic aneurysms or dissections when followed to 24 months, even when hypertension was induced. In vitro motility assays found decreased interaction of mutant SM α-actin filaments with SM myosin. Polymerization studies using total internal reflection fluorescence microscopy showed enhanced nucleation of mutant SM α-actin by formin, which correlated with disorganized and reduced SM α-actin filaments in Acta2R149C/+ smooth muscle cells (SMCs). However, the most prominent molecular defect was the increased retention of mutant SM α-actin in the chaperonin-containing t-complex polypeptide folding complex, which was associated with reduced levels of mutant compared with WT SM α-actin in Acta2R149C/+ SMCs. These data indicate that Acta2R149C/+ mice do not develop thoracic aortic disease despite decreased contraction of aortic segments and disrupted SM α-actin filament formation and function in Acta2R149C/+ SMCs. Enhanced binding of mutant SM α-actin to chaperonin-containing t-complex polypeptide decreases the mutant actin versus WT monomer levels in Acta2R149C/+ SMCs, thus minimizing the effect of the mutation on SMC function and potentially preventing aortic disease in the Acta2R149C/+ mice.

A RARE CASE OF LOCALIZED DISSECTION OF SINUS OF VALSALVA DIAGNOSED BY MULTIMODALITY IMAGING

TOPIC: Cardiovascular Disease TYPE: Fellow Case Reports INTRODUCTION: Sinus of Valsalva dissection is extremely rare and life threatening. It commonly occurs after coronary intervention and can involve right or left sinus of Valsalva. We present a rare case of spontaneous localized dissection of sinus of Valsalva involving non-coronary cusp which was diagnosed with multi-modality imaging. CASE PRESENTATION: 65 year old woman with history of non-ischemic cardiomyopathy was admitted to the hospital for management of new onset atrial fibrillation with rapid ventricular rate. Rhythm control approach was opted after the initial rate control. Transthoracic echocardiogram showed left ventricular ejection fraction of 35% and moderate aortic regurgitation. Transesophageal echocardiogram performed to evaluate for left atrial appendage thrombus prior to cardioversion revealed an aortic dissection limited to sinus of valsalva. She underwent a CTA aorta which was negative for dissection. Cardiac gated MRI was performed to evaluate her aortic root which showed a small intimal flap with limited dissection of sinus of Valsalva at non-coronary cusp of the aortic valve. On review of images and history, the dissection was thought to be chronic and probably related to a diagnostic cardiac catheterization that was performed a month before her admission. After discussion with cardiothoracic surgery decision was made to medically manage the patient with serial imaging given her poor functional status and chronicity of the limited dissection. On one month follow-up patient remained stable and asymptomatic. DISCUSSION: Aortic dissection confined to sinus of Valsalva is a rare but life-threatening. The incidence of this has not been reported in literature. These cases are mostly diagnosed during pre-operative TEE or incidentally. Localized sinus of Valsalva dissections is easily missed on a CTA as the temporal and spatial resolution in these areas are compromised due to large vibrations by aortic valve. TEE is superior in diagnosing these types of dissections. Gated cardiac MRI can be helpful in some cases. CONCLUSIONS: Aortic dissection localized to sinus of Valsalva presents a clinical challenge in terms of diagnosis and management. High index of suspicion and multimodality imaging approach is often required to arrive at the right diagnosis. Given the rarity of this condition the guidelines on the management are limited. REFERENCE #1: Fukui T. Management of acute aortic dissection and thoracic aortic rupture. J Intensive Care. 2018;6:15. Published 2018 Mar 1. REFERENCE #2: Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases Eur Heart J. 2014;35(41):2873-2926. REFERENCE #3: Hiratzka LF, et al ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. Catheter Cardiovasc Interv. 2010 Aug 1;76(2):E43-86. doi: 10.1002/ccd.22537. PMID: 20687249. DISCLOSURES: No relevant relationships by Shruti Hegde, source=Web Response No relevant relationships by Kalyan Potu, source=Web Response No relevant relationships by Omar Siddiqui, source=Web Response

THE ANESTHETIC MANAGEMENT OF EXTENSIVE AORTIC THORACIC ANEURYSM REPAIR WITH CLAMSHELL INCISION

Introduction Surgical repair of extensive thoracic aorta disease represents an interesting challenge, both surgical and anesthetic. We describe the surgical repair of an acute aortic dissection beginning in the aortic arch in relation with aortic coartation and a post coartation aneurism, and the aspects related to planning, management and perioperative care. The clamshell incision is associated with respiratory complications, bleeding and post-operative severe pain. Interruption of spinal cord blood supply is one of the causes of spinal cord injury after thoracic aortic aneurism repair. Aortic arch surgery requiring circulatory arrest bears significant risk of brain injury. Methods Descending aorta cannulation and perfusion, preservation of its posterior wall, lumbar paravertebral NIRS and femoral arterial invasive pressure monitoring were used as spinal cord protective strategies. Cerebral antegrade perfusion, initially unilateral and then bilateral, with BIS and cerebral NIRS monitoring were the key components of the cerebral protection strategy. A bilateral erector spinae plane block (BESPB) was performed to allow good pain control in the postoperative period, early extubation and rehabilitation. Intravenous antifibrinolytic, goal directed transfusion therapy and maintaining a coagulation friendly environment were the mainstays of the non-surgical hemostasis strategy. Results The patient was successfully extubated in the operating room presenting no neurological deficits. The surgical drains were removed on the fifth day; on the following day it was necessary to surgically remove part of the left thoracic drain, under combined anesthesia with the ipsilateral ESPB catheter. The remaining postoperative period was uneventful and the patient was discharged home in the 10th postoperative day. Discussion No subarachnoid catheter was placed (to drain cerebrospinal fluid to protect the spinal cord from ischemia), after discussing it in advance with the surgical team, given the risks associated with it and the protective strategy to be adopted: direct perfusion of the descending aorta, preservation of its posterior wall, lumbar paravertebral NIRS ant femoral arterial invasive pressure monitoring., in the intraoperative period, on table extubation and direct neurological monitoring, together with adequate systemic arterial pressures, in the immediate postoperative period. Good pain control with BESPB and on table extubation allowed for early rehabilitation

Early and mid-term outcomes of thoracic aortic reconstruction using the frozen elephant trunk technique: A single-center retrospective study

Background. The frozen elephant trunk (FET) technique for the treatment of both thoracic aortic aneurysms and dissections has become universally popular over the past two decades because extensive open surgical reconstruction of the thoracic aorta has been found to be associated with high complication and mortality rates or unfavourable long-term outcomes as it requires repeated interventions. The FET technique has also been shown to produce excellent, immediate and long-term results. Hence, it is important to evaluate the outcomes of thoracic aortic reconstruction using this technique.Aim. This study aimed to investigate immediate and long-term outcomes of the FET technique in patients with thoracic aortic diseases.Methods. We retrospectively analysed the pre-, intra- and post-operative data of 40 patients with distal aortic arch aneurysm who had undergone aortic arch reconstruction using the FET technique at Meshalkin National Research Medical Center from February 2012 to October 2020. To assess the early and long-term post-operative survival of these patients, we categorised them into group I (including 14 patients without aortic dissection) and group II (including 26 patients with type I and type III aortic dissections).Results. The in-hospital survival rates for groups I and II were found to be 68.5% and 95.9%, respectively (log rank, p = 0.048). Groups I and II did not differ significantly in the incidence of stroke (7.1% vs 7.7%, respectively; p = 0.724) and spinal cord ischaemia (14.3% vs 0%, respectively; p = 0.117). Long-term (1-, 3- and 5-year) survival rates in group II remained unchanged at 95.9%, whereas survival rates at 30 days, 6 months and 1 year in group I were 91.3%, 68.5% and 57%, respectively. The risk of mortality was 90% lower in group II than in group I, with a hazard ratio of 0.096 and a 95% confidence interval of 0.01–0.81 (p = 0.038). The rates of freedom from thoracoabdominal aortic interventions in group II were 91.8%, 83%, 64.7%, 59.3% and 59.3% at 30 days, 6 months, 1 year, 3 years and 5 years, respectively; these rates in group I were 90.9%, 75.7% and 75.7% at 30 days, 6 months and 1 year, respectively. There was no significant difference between the groups concerning thoracoabdominal aortic interventions (log rank, p = 0.587).Conclusion. The use of the FET technique in patients with thoracic aortic diseases is associated with acceptable rates of mortality and thoracoabdominal aortic interventions in immediate and long-term post-operative periods.Received 28 January 2021. Revised 28 April 2021. Accepted 29 April 2021.Funding: This work was carried out within the framework of the state task of the Ministry of Health of the Russian Federation (No. 121032300337-5).Conflict of interest: The authors declare no conflicts of interests.Contribution of the authors: The authors contributed equally to this article.

One-Stage Hybrid Total Aortic Arch and Descending Thoracic Aortic Repair is a Safe and Secure Procedure With Less Postoperative Complications for Extended Aortic Arch Aneurysms

Purpose Hybrid aortic arch repair (HAR) has been implemented for extended aortic arch and descending thoracic aortic disease since 2012 in our institution. This study aimed to estimate the early and mid-term efficacy and safety of HAR. Materials and Methods From 2007 to 2019, 56 patients underwent HAR for extended aortic arch disease, and 75 patients underwent total arch replacement (TAR) for arch-limited disease. HAR comprises 3 procedures: replacement of the aorta, reconstruction of all arch vessels, and thoracic endovascular aortic repair (TEVAR) from zone 0 to the descending aorta after cardiopulmonary bypass is off in 1 stage. The type II-1 HAR procedure, in which the ascending aorta and aortic arch distal to the brachiocephalic artery are replaced, was the most frequently selected procedure (40/56 patients). The outcomes of the type II-1 HAR procedure were compared with those of TAR using the Cox regression analysis. Results The median follow-up period was 36 months. In HAR, the operative mortality, in-hospital mortality, and postoperative permanent neurological deficits were not observed. The paraplegia rate was 1.8%. TEVAR-related complications occurred in 3 patients. Among the patients with non-ruptured atherosclerotic aortic arch aneurysm (31 type II-1 HAR patients and 36 TAR patients, the postoperative respiratory support time in those who underwent type II-1 HAR was quicker than in those who underwent TAR (p<0.01). The rate of 6 year freedom from all-cause death in type II-1 HAR (83.1%) was numerically higher than that in TAR (74.7%), and the rate of 6 year freedom from surgery-related complications in type II-1 HAR (90.3%) was numerically lower than that in TAR (96.9%) due to the occurrence of TEVAR-related complications, and the rate of 6 year freedom from reintervention to the descending thoracic aorta in type II-1 HAR (100%) seemed to be better than that in TAR (83.7%). However, Cox regression analysis did not reveal any statistical difference between the 2 procedures. Conclusions HAR, especially the type II-1 procedure, can treat extended aortic arch disease with acceptable survival outcomes. The development of TEVAR technology will further improve the outcomes of HAR in the future.