Repair of thoracic aortic aneurysm with bilateral aberrant subclavian artery.

We present a rare anatomical configuration of a 19-year-old woman, characterized by descending thoracic aortic aneurysm with right aberrant subclavian arteries with a Kommerell's diverticulum in a left aortic arch. The complexity of this vascular anomaly was accompanied by an anomalous origin of left subclavian artery. The patient underwent a single-stage open surgical repair via left thoracotomy under deep hypothermic circulatory arrest. The bilateral aberrant subclavian arteries were separately reconstructed in situ using hand-sewn branched grafts.

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals.

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. METHODS AND RESULTS: One hundred eighty-one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age- and sex-matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10-6 [95% CI, 1.67-3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20-18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin-1). There was increased frequency of both missense and loss of function variants in TAA individuals. CONCLUSIONS: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Causal relationship between immune cells and aortic aneurysms: a Mendelian randomization study.

OBJECTIVES: The causal association between immune cell traits and aortic aneurysm remains unknown. METHODS: We performed a bidirectional two-sample Mendelian randomization analysis to explore the causality between 731 immune cell characteristics and the risk of abdominal aortic aneurysm and thoracic aortic aneurysms through publicly available genetic data, respectively. To examine heterogeneity and horizontal pleiotropy, Cochran's Q test and MR-Egger intercept were utilized. Additionally, multivariable Mendelian randomization analysis and meta-analysis were performed in further analysis. RESULTS: We found that 20 immune phenotypes had a suggestive causality on abdominal aortic aneurysm, and 15 immune phenotypes had a suggestive causal effect on thoracic aortic aneurysm. After further false discovery rate adjustment (q value <0.1), CD20 on IgD+ CD38- B cell (q = 0.053) and CD127 on CD28+ CD4+ T cell (q = 0.096) were associated with an increased risk of abdominal aortic aneurysm, respectively, indicating a significant causality between them. After adjusting for smoking, there is still statistical significance between CD127 on CD28+ CD4+ T cell and abdominal aortic aneurysm. However, after adjusting for lipids, no statistical significance can be observed between CD127 on CD28+ CD4+ T cells and abdominal aortic aneurysm. Furthermore, there is still statistical significance between CD20 on IgD+ CD38- B cells and abdominal aortic aneurysm after adjusting for lipids and smoking, which was further identified by meta-analysis. CONCLUSIONS: We found a causal association between immune cell traits and aortic aneurysm by genetic methods, thus providing new avenues for future mechanism studies.

Validating a Curvature-Based Marker of Cervical Carotid Tortuosity for Risk Assessment in Heritable Aortopathies.

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies. METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298, P=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656, P=0.818). Baseline total absolute curvature correlated with aortic root diameter (r=0.456, P=0.004) and was independently associated with aortic events during the 4-year follow-up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02-6.85]). Baseline tortuosity index correlated with age (r=0.532, P<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79-4.51]). Finally, baseline total absolute curvature had good discrimination of 4-year outcomes (area under the curve=0.724, P=0.014), which may be prognostic or predictive. CONCLUSIONS: Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature-based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys-Dietz syndrome.

Surgical repair of an aortoesophageal fistula after salvage thoracic endovascular aortic repair: a case report.

BACKGROUND: An aortoesophageal fistula can prove to be fatal. Salvage thoracic endovascular aortic repair as a bridging therapy and radical surgery with thoracotomy should be considered while treating aortoesophageal fistula without spontaneous closure. Moreover, it is essential to select a technique that reduces the risk of reinfection. Here we report a rare case of a ruptured thoracic aortic aneurysm related to esophageal perforation by a fish bone that led to massive hematemesis and shock, and the surgical treatment of an aortoesophageal fistula that developed after salvage thoracic endovascular aortic repair. CASE PRESENTATION: A 70-year-old Japanese female patient was admitted with hematemesis, thoracic pain, and shock related to esophageal perforation of a ruptured descending aortic aneurysm caused by fish bone aspiration and esophageal perforation 1 month previously. An emergency thoracic endovascular aortic repair was performed. Postoperatively, an aortoesophageal fistula that remained open and a food intake-related increase in the inflammatory response was noted. Radical blood-vessel prosthesis implantation and fistula closure were performed. The patient's postoperative course was favorable and the patient was discharged 22 days after the blood vessel prosthesis implantation. CONCLUSION: Such a case of rupture of a descending aortic aneurysm related to perforation by a fish bone and an aortoesophageal fistula is considerably rare. Thus, we report the therapeutic strategy of this particular case and review the relevant literature.

The Rise of Endovascular Repair for Abdominal, Thoracoabdominal, and Thoracic Aortic Aneurysms.

BACKGROUND: Given changes in intervention guidelines and the growing popularity of endovascular treatment for aortic aneurysms, we examined the trends in admissions and repairs of abdominal aortic aneurysms (AAA), thoracoabdominal aortic aneurysms (TAAA), and thoracic aortic aneurysms (TAA). METHODS: We identified all patients admitted with ruptured aortic aneurysms and intact aortic aneurysms repaired in the Nationwide Inpatient Sample (NIS) between 2004-2019. We then examined the utilization of open, endovascular, and complex endovascular repair (OAR,EVAR,cEVAR) for each aortic aneurysm location (AAA,TAAA,TAA), alongside their resulting in-hospital mortality, over time. cEVAR included branched, fenestrated, and physician modified endograft. RESULTS: 715,570 patients were identified with AAA (87% Intact-Repairs, 13% Rupture-Admissions). Both intact AAA repairs and ruptured AAA admissions decreased significantly between 2004 and 2019 (intact 41,060-34,215,p<.01; ruptured 7,175-4,625,p=.02). Out of all AAA repairs done in a given year, the use of EVAR increased (2004-2019: intact 45%-66%,p<.01; ruptured 10%-55%,p<.01) as well as cEVAR (2010-2019: intact 0%-23%,p<.01; ruptured 0%-14%,p<.01). Mortality after EVAR of intact AAAs decreased significantly by 29% (2004-2019, 0.73%-0.52%,p<.01) while mortality after OAR increased significantly by 16% (2004-2019, 4.4%-5.1%,p<.01). In the study, 27,443 patients were identified with TAAA (80% Intact, 20% Ruptured). In the same period, intact TAAA repairs trended upwards (2004-2019 1,435-1,640,p=.055) and cEVAR became the most common approach (2004-2019, 3.8%-72%,p=.055). 141,651 patients were identified with ascending, arch, or descending TAA (90% Intact, 10% Ruptured). Intact TAA repairs increased significantly (2004-2019 4,380-10,855,p<.01). From 2017-2019, the mortality after OAR of descending TAAs increased and mortality after TEVAR decreased (2017-2019: OAR 1.6%-3.1%; TEVAR 5.2%-3.8%). CONCLUSION: Both intact AAA repairs and ruptured AAA admissions significantly decreased between 2004 and 2019. The use of endovascular techniques for the repair of all aortic aneurysm locations, both intact and ruptured, increased over the past two decades. Most recently in 2019, 89% of intact AAAs repairs, infrarenal through suprarenal, were endovascular (EVAR or cEVAR, respectively). cEVAR alone has risen to 23% of intact AAA repairs in 2019, from 0% a decade earlier. In this period of innovation, with many new options to repair aortic aneurysms while maintaining arterial branches, endovascular repair is now used for the majority of all intact aortic aneurysm repairs. Long-term data are needed to evaluate the durability of these procedures.

Giant Thoracic Aortic Aneurysm Rupture in a Patient with Extensive Atherosclerotic Disease.

Aneurysmal dilatations can affect any aortic segment and represent the result of various causes, atherosclerotic disease being the most common and frequently involved. We hereby illustrate a case of a patient with thoracic aortic aneurysm rupture due to extensive atherosclerotic disease, with multiple complex penetrating ulcerated atherosclerotic plaques located in the descending aorta. CT angiography evaluation included a comprehensive description of imaging features and extent of the thoracic aortic aneurysm, the presence of thrombus, relationship to adjacent structures and branches, associated complications. Teaching Point: Thoracic aortic aneurysm rupture due to extensive atherosclerotic disease with multiple penetrating ulcers.

Temporal evolution of ascending aortic aneurysm wall stress predicts all-cause mortality.

OBJECTIVES: Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality. METHODS: Male veterans with <5.5 cm ascending aortic aneurysms and computed tomography at baseline and 3- to 5-year follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. RESULTS: Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/year (95% confidence interval, 0.04-0.20) for aortic diameter, 0.41 mm/year (0.12-0.71) for aortic length, 1.19 kPa/year -5.94 to 8.33) for peak circumferential stress, and 0.48 kPa/year (-3.89 to 4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/year, 1.27 (95% CI, 1.02-1.60; P = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/year, 8.47 (95% CI, 2.42-30; P < 0.001). CONCLUSIONS: In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

The Value of Aortic Volume and Intraluminal Thrombus Quantification for Predicting Aortic Events after Endovascular Thoracic Aneurysm Repair.

Objectives: To assess the ability of the aortic aneurysm volume (AAV), aneurysmal lumen volume (ALV), and aneurysmal thrombus volume (ATV) to predict the need for aortic reintervention when using the maximal aortic diameter as a reference. Methods: This monocentric retrospective study included 31 consecutive patients who underwent successful thoracic endovascular aortic repair (TEVAR) to treat an atheromatous thoracic aortic aneurysm. All patients underwent clinical and computed tomography angiography (CTA) for 3 years after TEVAR. The patients were categorized into group 0 if no aortic reintervention was required during the follow-up period and categorized into group 1 if they experienced a type I or III endoleak or aneurysm diameter increase requiring intervention. The maximum aneurysm sac diameter and the AAV, ALV, and ATV were calculated using CTA images obtained preoperatively (T0) and at 6-12 months (T1), 24 months (T2), and 36 months (T3) postoperatively, and their changes over time were analyzed. Correlations between diameter and changes in AAV, ALV, and ATV were assessed, and the association between diameter and volume changes and reintervetion was examined. The cutoff values for predicting the need for reintervention was determined using a receiver operating characteristic (ROC) curve. The accuracy of volume change versus diameter change for predicting the need for reintervention was analyzed. Results: There were no significant differences in terms of the mean aneurysm diameter or AAV, ALV or ATV between the groups at preoperative CTA or after one year of follow-up imaging. The mean ATV was higher in group 1 than in group 0 at 2 years (187.6 ± 86.3 mL vs. 114.7 ± 64.7 mL; p = 0.057) and after 3 years (195.0 ± 86.7 mL vs. 82.1 ± 39.9 mL; p = 0.013). The maximal diameter was greater in group 1 than in group 0 at 3 years (67.3 ± 9.5 mm vs. 55.3 ± 12.6 mm; p = 0.044). The rate of AAV change between T0 and T1 was significantly higher in group 1 (7 ± 4.5%) than in group 0 (-6 ± 6.8%; p < 0.001). The rate of ATV change between T1-T3 was significantly higher in group 1 than in group 0 (34 ± 40.9% vs. -13 ± 14.4% (p = 0.041)); similar results were observed for the rate of ATV change between T2 and T3 (27 ± 50.1% for group 1 vs. -8 ± 49.5% in group 0 (p < 0.001)). According to our multivariate analysis, the annual growth rate for AAV between T0 and T1 was the only independent factor that was significantly associated with aortic reintervention (area under the curve (AUC) = 0.84, OR = 1.57, p = 0.025; optimal cutoff +0.4%). An increase in the annual growth rate of the ATV between T0 and T3 was independently associated with the need for aortic reintervention (area under the curve (AUC) = 0.90, OR = 1.11, p = 0.0347; optimal cutoff +10.1%). Conclusions: Aortic volume analysis can predict the need for aortic reintervention more accurately and earlier than maximal aortic diameter.

Single-cell sequencing reveals the impact of endothelial cell PIEZO1 expression on thoracic aortic aneurysm.

INTRODUCTION: Thoracic aortic aneurysm (TAA) is a severe vascular disease that threatens human life, characterized by focal dilatation of the entire aortic wall, with a diameter 1.5 times larger than normal. PIEZO1, a mechanosensitive cationic channel, monitors mechanical stimulations in the environment, transduces mechanical signals into electrical signals, and converts them into biological signals to activate intracellular signaling pathways. However, the role of PIEZO1 in TAA is still unclear. METHODS: We analyzed a single-cell database to investigate the expression level of PIEZO1 in TAA. We constructed a conditional knockout mouse model of Piezo1 and used the PIEZO1 agonist Yoda1 to intervene in the TAA model mice established by co-administration of BAPN and ANG-II. Finally, we explored the effect of Yoda1 on TAA in vitro. RESULTS AND DISCUSSION: We observed decreased PIEZO1 expression in TAA at both RNA and protein levels. Single-cell sequencing identified a specific reduction in Piezo1 expression in endothelial cells. Administration of PIEZO1 agonist Yoda1 prevented the formation of TAA. In PIEZO1 endothelial cell conditional knockout mice, Yoda1 inhibited TAA formation by interfering with PIEZO1. In vivo and in vitro experiments demonstrated that the effect of Yoda1 on endothelial cells involved macrophage infiltration, extracellular matrix degradation, and neovascularization. This study highlights the role of PIEZO1 in TAA and its potential as a therapeutic target, providing opportunities for clinical translation.

Deciphering the circulating immunological landscape of thoracic aortic aneurysm: Insights from a two-sample Mendelian randomization study.

Background: Thoracic Aortic Aneurysm (TAA) poses significant health risks due to aortic dilation. Recent evidence suggests a pivotal role for the immune-inflammatory response in the mechanism of aortic aneurysm formation. In this study, we aim to investigate the causal relationship between circulating immune cells and TAA. Methods: This study employs a two-sample Mendelian Randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics for 731 immune cell types and two TAA data from large-scale studies. Causal effects of both peripheral immune cells on TAA and TAA on peripheral immune cells are explored. To ensure more accurate results, we intersected the findings from two TAA data from large-scale studies, excluding results where the direction of the odds ratio (OR) was inconsistent. Findings: The study identifies specific immune cells associated with TAA. Notably, CD45+ NKT cell (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.91, 95CI%: 0.84-0.99 in CHIP + MGI study) and CD45+ HLA-DR + CD8+ T cells (OR: 0.95, 95CI%: 0.90-0.99 in FinnGen study; OR: 0.90, 95CI%: 0.82-0.99 in CHIP + MGI study) demonstrate a protective role against TAA. In addition, CD28+ CD45RA- CD8+ T cells (relative cell counts and absolute cell counts) and HVEM + CM + CD8+ T cells are adversely affected by TAA. Interpretation: The findings indicate that the potential protective influence exerted by specific subsets of peripheral NKT cells and CD8+ T cells in mitigating the development of TAA, while simultaneously highlighting the reciprocal effects of TAA on peripheral Treg cells subsets and T cell subsets. The complex interaction between immune cells and TAA could provide valuable clues for earlier detection and more efficacious treatment strategies for TAA.

Comparison between Zone 2 and Zone 3 distal anastomoses for aortic arch replacement in terms of invasiveness.

OBJECTIVES: Zone 2 anastomosis with total cervical branch reconstruction for acute type A aortic dissection and aortic arch aneurysms became possible after stent-graft introduction. This may be an easier procedure and reduce the risk of recurrent laryngeal nerve palsy. Therefore, this study aimed to compare the outcomes between Zone 2 and Zone 3 distal anastomoses. METHODS: After evaluating the patient data in our institute between April 2016 and April 2022, the patients in whom distal anastomosis was performed at Zone 2 with a stent-graft were defined as the Zone 2 group (n = 70). The patients in whom distal anastomosis was performed at Zone 3 were defined as the Zone 3 group (n = 24). RESULTS: The incidence of new-onset recurrent nerve palsy was one patient (1.4%) in the Zone 2 group and six patients (25.0%) in the Zone 3 group (p < 0.001). The lower body perfusion arrest time was 44.3 ± 9.1 min in the Zone 2 group and 52.9 ± 12.8 min in the Zone 3 group (p = 0.005). There were no significant differences in in-hospital mortality and morbidities. Multivariable analysis showed that only age was an independent predictor of overall mortality. CONCLUSIONS: Performing distal anastomosis at Zone 2 with a frozen elephant trunk or stent-graft reduced the lower body perfusion arrest time and possibly prevented recurrent nerve palsy.

Complex genotype-phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes.

BACKGROUND: Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins. METHODS: The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11. RESULTS: The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006). CONCLUSION: This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

Thoracic aortic aneurysm in an adolescent with intraoperative discovery of contained rupture: a case report.

Background: As surgical recommendations in adults based on size criteria of ascending aortic aneurysms become more refined, criteria for childhood/adolescence remains less clear. Multiple pathologic factors may predispose younger patients to thoracic aortic aortopathy and increase the risk of rupture. An evolving field of research is how to identify thoracic aortic dilation earlier in patients, risk stratify, and to obtain objective measures beyond size for proceeding with surgical intervention in order to prevent catastrophic thoracic aortic dissection. Case Description: We report an adolescent case of dilated ascending aortic aneurysm with a functionally unicuspid/bicuspid aortic valve. This patient was taken to surgery electively, given the gradual increasing size of the ascending aorta. Intraoperatively, there was an unexpected intraoperative finding of a contained aortic rupture. The patient underwent an aortic root replacement with mechanical valve composite graft and coronary artery reimplantation (modified Bentall) with ascending hemiarch replacement. The patient did well with no post-operative complications. Aortic pathology and genetic analysis were performed. The patient was discovered to have a heterozygous variant in PTPN11 which is typically associated with Noonan syndrome; however, this is not known to be associated with aortopathy. Conclusions: As criteria for surgical intervention in adult thoracic ascending aortic aneurysms continues to evolve, this case illustrates challenges when determining the optimal criteria for surgical intervention in adolescent patients.

Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection.

BACKGROUND: We aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. METHODS: Consecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between 2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P), variants of uncertain significance, and gene-negative (Gen-N) groups. RESULTS: A total of 407 patients were included: mean age 53.7 ± 15.4 years, 64.4% men, and 38% with reported family history of TAAD. Thirty-seven (9.1%) were Gen-P; 147 (36.1%) had a variant of uncertain significance. The maximal aneurysm diameter was 4.78 mm larger in Gen-P than the other groups (P < .001). In 162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs 0.89 mm/year, respectively; P < .001). Aneurysms were 20% more likely to require surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. CONCLUSIONS: While aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria.

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.

The causal relationship between thoracic aortic aneurysm and immune cells: a mendelian randomization study.

One of the pathogenic causes of thoracic aortic aneurysm (TAA), a dangerous vascular condition that can cause aortic rupture, is autoimmune disorders. Currently, immune cell clustering is becoming more and more refined, and the specific immune cell phenotypes involved are yet unknown. Here, we want to clarify the causal link between TAA risk and 731 immune cell traits. There was a Mendelian randomization analysis (MR). We discovered that the presence of TAA led to an increase in CD45 on CD33- HLA-DR- myeloid cells, an increase in CD45 on natural killer cells, and a decrease in FSC-A on granulocytes after applying FDR correction. Our research also revealed a strong correlation between the incidence of TAA and an increase in immune cells with CD3 on CD39+ CD4+, and CD25 on IgD- CD27- phenotypes. Through genetic techniques, our research has shown the intimate relationship between immune cells and TAA, offering direction for future clinical investigations.

Long-term results of etiology-based thoracic endovascular aortic repair: a single-center experience.

The use of thoracic endovascular aortic repair (TEVAR) for thoracic aortic aneurysm (TAA) and Stanford type B aortic dissection (TBAD) has been increasing; however, in terms of etiology, the differences of long term after TEVAR outcomes remain unexplored. Thus, we investigated etiology-specific long-term results of TEVAR for TAA and TBAD. A total of 421 TEVAR procedures were performed at our institution from July 2007 to December 2021; 249 TAA cases and 172 TBAD cases were included. Traumatic aortic dissection and aortic injury cases were excluded. The mean observation duration was 5.7 years. The overall 30-day mortality rate was 1.4% (n = 6), with 1.2% (n = 3) in the TAA group and 1.7% (n = 3) in the TBAD group. The overall incidence of postoperative stroke was 0.9% (n = 4), with 1.2% (n = 3) and 0.6% (n = 1) in the TAA and TBAD groups, respectively (p = 0.90). Paraplegia developed in 1.7% (n = 7) of patients, with 2.4% (n = 6) in the TAA group and 0.6% (n = 1) in the TBAD group. Freedom from aortic-related death was not significantly different between the two etiologies; however, thoracic reintervention was more common in the TBAD group (p = 0.003), with endoleak being the most common indication for reintervention. Additionally, retrograde type A aortic dissection occurred in four TBAD cases, while migration occurred in three TAA cases. The perioperative results of TEVAR for TAA and TBAD were satisfactory. The long-term results were unfavorable owing to the occurrence of etiology-specific and common complications. In terms of the high frequency of reintervention, the long-term complications associated with TEVAR are etiology specific.