Heritable Thoracic Aortic Disease Research Articles

Genetic aortopathies: a case-based approach to multidisciplinary program development.

The incorporation of genetic counseling and testing is essential to evaluation and management of thoracic aortic disease in patients under 60 years of age and those with family histories suspicious for heritable thoracic aortic disease and disorders associated with increased risk for acute type-A aortic dissection. As many as 20% of individuals with thoracic aortic disease under the age of 60 years have autosomal dominant patterns of inheritance. A considerable number of heritability factors remain undefined for these families. Genetic aortopathy programs require a collaborative approach including cardiovascular specialists and surgeons, medical geneticists, genetic counselors, and allied healthcare professionals. Comprehensive evaluation and management of these patients includes collection of detailed phenotypic data to inform the broader community and identify new associated and causative genes of interest, genetic modifiers, and other risk factors. These programs optimize outcomes and reduce the overall burden in the population of acute aortic dissection and related comorbidities.

Similarity of aortic events between siblings with heritable thoracic aortic diseases: Clinical analysis focusing on identical twins and same-sex siblings.

Similarity of aortic events between siblings with heritable thoracic aortic diseases: Clinical analysis focusing on identical twins and same-sex siblings.

Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management.

Heritable thoracic aortic disease puts patients at risk for aortic aneurysms, rupture, and dissections. The diagnosis and management of this heterogenous patient population continues to evolve. Last year, the American Heart Association/American College of Cardiology Joint Committee published diagnosis and management guidelines for aortic disease, which included those with genetic aortopathies. Additionally, evolving research studying the implications of underlying genetic aberrations with new genetic testing continues to become available. In this review, we evaluate the current literature surrounding the diagnosis and management of heritable thoracic aortic disease, as well as novel therapeutic approaches and future directions of research.

Comparison of open thoracoabdominal repair for chronic aortic dissections and aneurysms

ObjectiveAortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm. MethodsWe retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Logistic regression identified predictors of operative mortality and adverse events. Time-to-event analyses examined survival, death, repair failure, subsequent progressive repair, and survival free of failure or subsequent repair. ResultsCompared with patients with non-dissection aneurysm, those with chronic dissection were younger, had fewer atherosclerotic risk factors, and were more likely to have heritable thoracic aortic disease and undergo extent II repair. The operative mortality rate was 8.5% (n = 296) overall and was higher in non-dissection aneurysm patients (n = 217; 9.2%) than in chronic dissection patients (n = 79; 7.1%; P = .03). Adverse events were less frequent (P = .01) in patients with chronic dissection (n = 145; 13.0%), 22 (2.0%) of whom had persistent paraplegia. Chronic dissection was not predictive of operative mortality (P = .5) or adverse events (P = .6). Operative mortality and adverse events, respectively, were independently predicted by emergency repair (odds ratio [OR], 3.46 and 2.87), chronic kidney disease (OR, 1.74 and 1.81), extent II TAAA repair (OR, 1.44 and 1.73), increasing age (OR, 1.04/year and 1.04/year), and increasing aortic cross-clamp time (OR, 1.02/minutes and 1.02/minutes). Patients with chronic dissection had lower 10-year unadjusted mortality (42% vs 69%) but more frequent repair failure (5% vs 3%) and subsequent repair for progressive aortic disease (11% vs 5%) than patients with non-dissection aneurysm (P < .001); these differences were no longer statistically significant after adjustment. ConclusionsOutcomes of open TAAA repair vary by aortic disease type. Emergency repairs and atherosclerotic diseases most commonly occur in patients with non-dissection aneurysm and independently predict operative mortality. Repair of chronic dissection is associated with low rates of adverse events, including operative mortality and persistent paraplegia, along with reasonable late survival and good durability. However, patients with chronic dissection tend to more commonly undergo subsequent repair to treat progressive aortic disease, which emphasizes the need for robust long-term imaging surveillance protocols.

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections.

The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). The study's findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

Diagnosis and treatment of cardiovascular disease in patients with heritable connective tissue disorders or heritable thoracic aortic diseases.

Patients with heritable connective tissue disorders (HCTDs), represented by Marfan syndrome, can develop fatal aortic and/or arterial complications before age 50. Therefore, accurate diagnosis, appropriate medical treatment, and early prophylactic surgical treatment of aortic and arterial lesions are essential to improve prognosis. Patients with HCTDs generally present with specific physical features due to connective tissue abnormalities, while some patients with heritable thoracic aortic diseases (HTADs) have few distinctive physical characteristics. The development of genetic testing has made it possible to provide accurate diagnoses for patients with HCTDs/HTADs. This review provides an overview of the diagnosis and treatment of HCTDs/HTADs, including current evidence on cardiovascular interventions for this population.

Abstract 15404: Exercise and Sports Participation is Associated With Improved Quality of Life in Young Patients With Heritable Thoracic Aortic Disease

Introduction: Traditionally, patients with heritable thoracic aortic disease (HTAD) have been restricted from competitive sports due to concerns over acute aortic dissection. Patients with HTAD also exhibit lower quality of life (QOL) and physical fitness than general populations. Murine data suggests exercise improves aortic health and does not contribute to aortic enlargement. Hypothesis: Exercise and competitive sports participation will be associated with improved QOL in HTAD patients. Aims: Investigate the effect of lifetime exercise ‘dose’ and competitive sports participation on QOL in patients aged 15-35 with syndromic HTAD [Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS)] and non-syndromic HTAD. Methods: This cross-sectional study employed a questionnaire to assess lifetime exercise exposure and utilized the PedsQL QOL Inventory. We developed an Exercise Score (ES) to quantify lifetime exercise exposure based on questionnaire results (3 points for competitive sports season, 1 point for recreational sport season. Questionnaires were completed via telephone interview with complimentary medical chart review. Results: Of the forty patients enrolled, the mean age was 26 years. The diagnosis was MS in 82.5%. Despite 87.5% of patients being restricted by their cardiologist, 65% reported competitive sports participation and 92.5% reported some lifetime recreational exercise. The median ES for our population was 19. Participants with an ES greater than the median had a significantly better total QOL score compared to participants with an ES below the median (78 vs 65, p=0.03). There was no difference in aortic size or need for surgical intervention between those above and below the median ES. This also held true for those who did and did not participate in competitive sports. There was a strong positive correlation between the amount of current exercise (days-per-week) and total QOL score (corr=0.55, p&lt;0.001). Conclusions: Increased lifetime exercise exposure and current physical activity levels were associated with improved QOL in young adults with HTAD. There did not appear to be a detrimental effect of exercise on aortic size or need for surgical intervention.

Outcomes After Extent I Thoracoabdominal Aortic Repair: Focus on Heritable Aortic Disease

BackgroundCrawford extent I thoracoabdominal aortic aneurysm (TAAA) repairs are increasingly performed by an endovascular approach, including in patients with heritable thoracic aortic disease (HTAD). We evaluated outcomes after open extent I TAAA repair in patients with and without HTAD. MethodsThis retrospective study included 992 patients (median age, 67 years; quartile 1-quartile 3, 57-73 years) who underwent extent I TAAA (1990-2022), stratified by the presence of HTAD (n = 177 [17.8%]). Patients with HTAD had genetic aortopathies or presented at age ≤50 years, and 35% (62 of 177) had Marfan syndrome. Logistic regression was used to identify predictors of operative death and adverse event, a composite of operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Long-term outcomes were analyzed with competing risks analysis. ResultsPatients with HTAD had lower rates of operative mortality (1.7% vs 7.0%, P = .01) and composite adverse event (2.8% vs 12.3%, P < .001) than non-HTAD patients. Most HTAD patients were discharged home (92.6% vs 76.9%, P < .001). Predictors of operative death were increasing age, aortic dissection, tobacco use, chronic symptoms, and rupture. Predictors for adverse event were increasing age, acute symptoms, chronic dissection, and rupture. Patients with HTAD had substantially better repair-failure-free survival (P < .001). ConclusionsOpen extent I TAAA repair was effective in patients with HTAD, with low operative mortality and adverse event rates, better late survival, and excellent long-term durability, making a compelling argument for preferring open repair in these patients.

Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome

BackgroundThe Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown.MethodsWhole exome...

Outcomes of aortic root replacement in patients with Marfan syndrome: the role of valve-sparing and valve-replacing approaches.

Marfan syndrome (MFS) is a heritable thoracic aortic disease with pervasive cardiovascular effects, including commonly, a dilated aortic root. Traditionally, the root is replaced using a mechanical composite valve graft (CVG); however, this valve-replacing (VR) approach necessitates a lifelong regimen of anticoagulation with a potential for late bleeding complications. In time, valve-sparing (VS) approaches were developed. Today, several options for aortic root replacement (ARR) exist; each has advantages and disadvantages that helps inform choice. The Aortic Valve Operative Outcomes in Marfan Patients (AVOMP) is a multi-center international registry to analyze clinical outcomes of ARR in MFS patients using either VR or VS techniques to better elucidate choice. We summarize outcomes of AVOMP and present our own experience. We performed 223 consecutive elective ARR [1991-2023] in patients with MFS; 15 such repairs were included in AVOMP. Repairs included 113 (51%) using a mechanical CVG, 62 (28%) using a VS approach, and 48 (22%) using a bioprosthetic root. Many patients underwent aortic arch repair (30% to 54% by type). The median patient age was 38 [29-52] years. In comparing VS and VR groups, patients were similar in age and rates of major comorbidities and symptoms. Patients with VR repair had a more complex aortic history. The rate of redo sternotomy was 24% (n=54). Operative death was uncommon [4% overall (10/223); ranging from 2% to 8% by type], and stroke was rare [1/223 (<1%)]. Late survival and reoperation differed by operative approach; survival was improved in patients who underwent VS repair. We found that repair in patients with MFS undergoing ARR resulted in low operative risk. Our late results were similar to those of AVOMP in that patients undergoing VS repair tended to experience greater rates of valvular-structural deterioration, although this did not appear to impact survival.

Management of Visceral Artery Patch Aneurysms and Segmental Artery Patch Aneurysms Following Open Thoracoabdominal Aortic Aneurysm Repair

Segmental intercostal/lumbar and visceral arteries are often reimplanted as a patch with surrounding native aortic tissue during open thoracoabdominal aortic aneurysm (TAAA) repair to preserve perfusion of the spinal cord and expedite visceral revascularization. However, late aneurysmal degeneration of the aortic tissue in the patch is a known, albeit infrequent, complication of this technique. The objective of this study was to describe our experience with management of visceral artery patch (VAP) aneurysms and segmental artery patch (SAP) aneurysms following TAAA repair. We retrospectively identified 57 patients (median age, 62 years; range, 50-73 years) who underwent VAP aneurysm and/or SAP aneurysm repair in our single practice (1986-2021). Median time from initial TAAA repair to patch aneurysm repair was 9 years (range, 5-12 years). Of these 57 repairs, 37 were for VAP aneurysm, 13 were for SAP aneurysm, and 7 were for both (Table). All 37 VAP aneurysms were repaired with open TAAA reoperations, while SAP aneurysms were addressed with either open repair (n = 13) or endovascular exclusion with thoracic aortic endografts (n = 7). Twenty-three patients (40%) had heritable thoracic aortic disease, of whom 17 had Marfan syndrome (30%). Crawford extent II repair was the most common preceding TAAA repair (n = 35, 61%). Patients presenting with patch aneurysm were often symptomatic (n = 41; 72%). Additionally, eight patients (14%) presented with patch aneurysm rupture. Early outcomes included operative mortality and adverse event, a composite variable comprised of operative death or persistent renal failure necessitating dialysis, paraplegia, paraparesis, or stroke. Operative mortality was 9% (n = 5); however, no operative deaths occurred in those treated with endovascular repair. The adverse event rate was 11% (n = 6), including four patients (7%) who developed persistent renal failure requiring dialysis following their repair. Only one patient (2%) experienced a stroke postoperatively. No patients experienced persistent paraplegia, including those who had endograft coverage of their intercostal patch without intercostal revascularization. Of 13 open SAP aneurysm repairs, 7 were performed with subsequent intercostal artery reimplantation. Left heart bypass was not used in any repairs; however, other adjuncts such as cerebrospinal fluid drainage (n = 27; 47%) and cold renal perfusion (n = 38; 67%) were used frequently. Most patients were discharged home (n = 49; 86%) (median length of hospital stay, 10 days; range, 9-14 days). Reoperative open VAP and SAP aneurysm repair is technically challenging; however, it can be performed with reasonable outcomes. Isolated SAP aneurysms can be safely managed with endovascular exclusion with promising results.TablePreoperative characteristics, operative details, and early outcomes in 57 visceral artery patch (VAP) aneurysm and segmental artery patch (SAP) aneurysm repairsVariablePatch aneurysm (n = 57)Age, years62 [50-73]Male sex30 (53)Time from initial TAAA repair to patch aneurysm repair, years9 [5-12]Heritable thoracic aortic disease23 (40)Tobacco use39 (68)Symptomatic41 (72)Rupture8 (14)Prior extent II repair35 (61)Urgent or emergency repair13 (23)Pseudoaneurysm at site of patch aneurysm15 (26)Open repaira50 (88) VAP aneurysm only37 (74) SAP aneurysm only6 (12) Both7 (14)Endovascular repair7 (12) VAP aneurysm0 SAP aneurysm7 (100)Cerebrospinal fluid drainage27 (47)Left heart bypass0Adverse event6 (11)Operative death5 (9)Persistent paraplegia0Persistent renal failure4 (7)Length of intensive care unit stay, days4 [3-6]Length of hospital stay, days10 [9-14]Discharged home49 (86)Values are number (%) or median (quartile 1-quartile3 [Q1-Q3]). Variables with missing data are clarified by available sample size.aPercentages in the open and endovascular repair subgroups are expressed as percentage of total open or endovascular repairs, respectively. Seven open repairs were performed in patients who had both VAP and SAP aneurysms repaired simultaneously. Open table in a new tab

Analysis of Genetic Predisposition In Acute Aortic Syndrome In New Zealand

Objective: The natural history and progression of acute aortic syndrome (AAS) has been suggested to be more severe in patients with a familial history or a syndromic AAS.1 One of these being aortic dissection, in which the underlying aetiology is autosomal dominant gene variants in the heritable thoracic aortic disease (HTAD) genes. In New Zealand, large ethnic disparities in the presentation and incidence for patients presenting with AAS have been documented.2 Despite the underlying risk factors, the present authors postulate that there may be an increased genetic predisposition in select patient cohorts. The aim of this study was to analyse genetic variances in patients presenting with AAS.

Association Between Genetic Diagnosis and Clinical Outcomes in Patients With Heritable Thoracic Aortic Disease.

Background Differences in the clinical course of heritable thoracic aortic disease based on the disease-causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis. Methods and Results We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1, FBN1 (n=344); Group 2, TGFBR1, TGFBR2, SMAD3, or TGFB2 (n=74); Group 3, COL3A1 (n=60); and Group 4, ACTA2 or MYH11 (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5 years (P=0.36). Patients with gene variants related to transforming growth factor-β signaling had a significantly higher rate of subsequent events than those with FBN1 variants (adjusted hazard ratio, 2.33 [95% CI, 1.60-3.38]; P<0.001). Regarding the incidence of aortic dissection, there were no significant differences among the 4 groups in male patients (36.3%, 34.3%, 21.4%, and 54.2%, respectively; P=0.06). Female patients with COL3A1 variants had a significantly lower incidence than female patients in the other 3 groups (34.2%, 59.0%, 3.1%, and 43.8%, respectively; P<0.001). Conclusions Gene variants related to transforming growth factor-β signaling are associated with a higher incidence of subsequent cardiovascular events than FBN1 variants. COL3A1 variants might be related to a lower incidence of aortic dissection than other gene variants in women only. Identifying the genetic background of patients with heritable thoracic aortic disease is important for determining appropriate treatment.

Genetically Triggered Thoracic Aortic Disease: Who Should be Tested?

Up to 25% of patients with thoracic aortic disease have an underlying Mendelian pathogenic variant. This is a heterogeneous group of disorders known as heritable thoracic aortic diseases (HTAD). Diagnosing associated pathogenic gene variants and syndromes is critical, as the underlying genetics have an implication in medical management, surveillance, thresholds for surgical intervention, surgical risk, pregnancy risk, and risk of inheritance by the offspring. Recently released 2022 American College of Cardiology/American Heart Association guidelines for the diagnosis and management of aortic diseases provide specific recommendations to identify patients at risk for heritable conditions and who should undergo genetic testing.

An FBN1 deep intronic variant is associated with pseudoexon formation and a variable Marfan phenotype in a five generation family.

Exome sequencing of genes associated with heritable thoracic aortic disease (HTAD) failed to identify a pathogenic variant in a large family with Marfan syndrome (MFS). A genome-wide linkage analysis for thoracic aortic disease identified a peak at 15q21.1, and genome sequencing identified a novel deep intronic FBN1 variant that segregated with thoracic aortic disease in the family (LOD score 2.7) and was predicted to alter splicing. RT-PCR and bulk RNA sequencing of RNA harvested from fibroblasts explanted from the affected proband revealed an insertion of a pseudoexon between exons 13 and 14 of the FBN1 transcript, predicted to lead to nonsense mediated decay (NMD). Treating the fibroblasts with an NMD inhibitor, cycloheximide, greatly improved the detection of the pseudoexon-containing transcript. Family members with the FBN1 variant had later onset aortic events and fewer MFS systemic features than typical for individuals with haploinsufficiency of FBN1. Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies.

Analysis of the relative risks of first aortic events linked to hereditary thoracic aortic diseases

Objective: Heritable Thoracic Aortic (HTA) disease is characterized by pathogenic variants in eleven genes, even though there is insufficient data to categorise the First Aortic Events (FAE) risk related to such genes. Methods: The chance of FAE was estimated for a retrospective cohort of probands and families with rare mutations in seven genes for HTA disease (n=1,028) using the gene variables, pathogenic variation class, gender, proband status, and region of recruitment. Results: Both the Smooth Muscle Contraction (SMC) genes (MYLK, ACTA2, and PRKG1; P =0.002) and the Loeys-Dietz syndrome genes (TGFBR1, TGFBR2, TGFB2, and SMAD3; P&lt; 0.0001), which encodes a protein in the Transforming Growth Factor (TGF)-b pathway, showed significant variations in aortic event risk. In contrast to those who received elective aneurysm treatment, participants with variations in TGFBR2 had a reduced cumulative incidence of type-A aortic dissection. Participants with mutations in MYLK, ACTA2, PRKG1, and SMAD3 had consistently higher incidences of type-A aortic dissection. Compared to other genes, PRKG1, ACTA2, and TGFBR2 exhibited a higher Cumulative Incidence (CI) of type B aortic dissection. Even if proband status, gender, and recruiting location were taken into consideration, there was a noticeably higher risk of an FAE with childhood onset associated with specific polymorphisms in the gene ACTA2 and TGFBR2. Conclusion: Data on FAE in people with HTA disease that are gene and variant-specific assist personalized aortic monitoring and clinical care.

The Role of Genetic Testing in Patients with Heritable Thoracic Aortic Diseases

Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20-25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients' management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management.

Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases.

In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce. To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation.

Straightforward Contemporary Step-by-Step Approach to Aortic Root Replacement With Valve-Sparing Tricuspid Aortic Valve Repair

Valve-sparing aortic root replacement (VSARR) has become an appealing choice for replacing an aneurysmal root when the patient's anatomic characteristics are favorable, especially in patients with heritable thoracic aortic disease. It is a technically challenging procedure, and the learning curve is considerable. This approach's chief advantages are that the patient's own aortic valve apparatus is preserved, the repair (in expert hands) is durable, and it avoids the need for lifelong anticoagulation associated with the mechanical valves in the aortic root prostheses. In this report, we provide a step-by-step approach for aortic root replacement in patients with a tricuspid aortic valve suitable for VSARR. Valve-sparing aortic root replacement (VSARR) has become an appealing choice for replacing an aneurysmal root when the patient's anatomic characteristics are favorable, especially in patients with heritable thoracic aortic disease. It is a technically challenging procedure, and the learning curve is considerable. This approach's chief advantages are that the patient's own aortic valve apparatus is preserved, the repair (in expert hands) is durable, and it avoids the need for lifelong anticoagulation associated with the mechanical valves in the aortic root prostheses. In this report, we provide a step-by-step approach for aortic root replacement in patients with a tricuspid aortic valve suitable for VSARR. Commentary on Baylor's Technique of Aortic Valve ReimplantationOperative Techniques in Thoracic and Cardiovascular SurgeryPreviewDoctors Preventza, Huu, and Coselli described the technique they use to do reimplantation of the aortic valve to treat aortic root aneurysms.1 I will limit my comments to areas that I disagree with what was written in their manuscript. Full-Text PDF

HTAD patient pathway: Strategy for diagnostic work-up of patients and families with (suspected) heritable thoracic aortic diseases (HTAD). A statement from the HTAD working group of VASCERN

Heritable thoracic aortic diseases (HTAD) are rare pathologies associated with thoracic aortic aneurysms and dissection, which can be syndromic or non-syndromic. They may result from genetic defects. Associated genes identified to date are classified into those encoding components of the (a) extracellular matrix (b) TGFβ pathway and (c) smooth muscle contractile mechanism. Timely diagnosis allows for prompt aortic surveillance and prophylactic surgery, hence improving life expectancy and reducing maternal complications as well as providing reassurance to family members when a diagnosis is ruled out. This document is an expert opinion reflecting strategies put forward by medical experts and patient representatives involved in the HTAD Rare Disease Working Group of VASCERN. It aims to provide a patient pathway that improves patient care by diminishing time to diagnosis, facilitating the establishment of a correct diagnosis using molecular genetics when possible, excluding the diagnosis in unaffected persons through appropriate family screening and avoiding overuse of resources. It is being recommended that patients are referred to an expert centre for further evaluation if they meet at least one of the following criteria: (1) thoracic aortic dissection (<70 years if hypertensive; all ages if non-hypertensive), (2) thoracic aortic aneurysm (all adults with Z score >3.5 or 2.5–3.5 if non-hypertensive or hypertensive and <60 years; all children with Z score >3), (3) family history of HTAD with/without a pathogenic variant in a gene linked to HTAD, (4) ectopia lentis without other obvious explanation and (5) a systemic score of >5 in adults and >3 in children. Aortic imaging primarily relies on transthoracic echocardiography with magnetic resonance imaging or computed tomography as needed. Genetic testing should be considered in those with a high suspicion of underlying genetic aortopathy. Though panels vary among centers, for patients with thoracic aortic aneurysm or dissection or systemic features these should include genes with a definitive or strong association to HTAD. Genetic cascade screening and serial aortic imaging should be considered for family screening and follow-up. In conclusion, the implementation of these strategies should help standardise the diagnostic work-up and follow-up of patients with suspected HTAD and the screening of their relatives.