Fate of the unoperated ascending thoracic aortic aneurysm: three-decade experience from the Aortic Institute at Yale University.

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.

Evidence Accumulates: Patients with Ascending Aneurysms Are Strongly Protected from Atherosclerotic Disease.

Ascending thoracic aortic aneurysms may be fatal upon rupture or dissection and remain a leading cause of death in the developed world. Understanding the pathophysiology of the development of ascending thoracic aortic aneurysms may help reduce the morbidity and mortality of this disease. In this review, we will discuss our current understanding of the protective relationship between ascending thoracic aortic aneurysms and the development of atherosclerosis, including decreased carotid intima-media thickness, low-density lipoprotein levels, coronary and aortic calcification, and incidence of myocardial infarction. We also propose several possible mechanisms driving this relationship, including matrix metalloproteinase proteins and transforming growth factor-ß.

"Big Data" Analyses Underlie Clinical Discoveries at the Aortic Institute.

This issue of the Yale Journal of Biology and Medicine (YJBM) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets). 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis: 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA.

Aortic Valve Replacement in the Failing Left Ventricle: Worthwhile?

Purpose: According to the 2020 American College of Cardiology/American Heart Association guidelines, the aortic valve should be replaced in the setting of severe aortic stenosis or regurgitation, independent of left ventricular function (even for EF < 55%). However, in clinical practice, especially in a very low EF range, surgeons may avoid surgical aortic valve replacement (SAVR) because of concern over operative risk. This study examines outcomes of patients with EF ≤ 35% undergoing SAVR. Methods: From 2004 to 2019, 895 patients underwent SAVR for aortic stenosis (AS) and/or regurgitation (AR) by a single surgeon at our institution. From among these, 40 patients (4.47%) had an ejection fraction (EF) of 35% or less, forming the study group. Intra-aortic balloon pump was placed intraoperatively prophylactically pre-bypass in 18 out of the 40. Preoperative and post-operative echocardiograms were compared to determine changes in ejection fraction. Mid-term survival was assessed. Results: 16 patients presented with AS, 20 with AR, and 4 with a combination of AS and AR. Hospital survival was 97.5% (one patient death). The average ejection fraction progressively improved over time from 26% initially to 46% mid-term with mean follow-up of 43 months (0.1-140.7). Remarkably, five-year survival was comparable between the study group and an age- and gender-matched general population (p = 0.834). Downward trends in LV end-diastolic diameter and end-systolic diameter were seen. The former achieved statistical significance (6.0 cm to 5.3 cm; p = 0.0046), while the latter fell slightly short (4.8 cm to 4.1 cm; p = 0.056). Patients in whom an IABP was used had lower EFs than those without IABP (range 10-35, mean 23% vs. 15-35%, mean 27.6%). The EFs of the three subgroups improved significantly postoperatively (p < 0.001 for AS, p = 0.002 for AR, and p = 0.046 for AS and AR). Conclusions: Surgical AVR can be done safely in patients with a failing LV with EF ≤ 35%. Significant improvements in the ejection fraction are seen over time. We believe there is a role for prophylactic pre-bypass IABP. Five-year survival is normalized. Surgeons should not hesitate to perform AVR in these highly jeopardized patients.

Interstage mortality in two-stage elephant trunk surgery.

PURPOSE: Diffuse mega-aorta is challenging. Prior studies have raised concerns regarding the safety of the open two-stage elephant trunk (ET) approach for extensive thoracic aortic aneurysm (TAA), specifically in regard to interstage mortality. This study evaluates the safety of the two-stage ET approach for management of extensive TAA. METHODS: Between 2003 and 2018, 152 patients underwent a Stage I ET procedure by a single surgeon (mean age 64.5 ± 14.8). Second stage ET procedure was planned in 60 patients (39.4%) and to-date has been performed in 54 patients (90%). (in the remaining patients, the ET was prophylactic for the long-term, with no plan for near-term utilization). RESULTS: In-hospital mortality after the Stage I procedure was 3.3% (5/152). In patients planned for Stage II, the median interstage interval was 5 weeks (range: 0-14). Of the remaining six patients with planned, but uncompleted Stage II procedures, five patients expired from various causes in the interval period (interstage mortality of 8.3%). There were no cases of aortic rupture in the interstage interval. Stage II was completed in 58 patients (including four unplanned) with a 30-day mortality of 10.3% (6/58). Seven patients developed strokes after Stage II (12%), and three patients (5.1%) developed paraplegia. CONCLUSIONS: The overall mortality, including Stage I, interstage interval, and Stage II was 18.6%. This substantial cumulative mortality for the open two-staged ET approach for the treatment of extensive TAA appears commensurate with the severity of the widespread aortic disease in this patient group. Fear of interstage rupture should not preclude the aggressive Two-Stage approach to the management of extensive TAA.

Natural history and management of Kommerell's diverticulum in a single tertiary referral center.

OBJECTIVE: The Kommerell diverticulum (KD) is an extremely rare developmental abnormality of the aorta related to an aberrant subclavian artery (ASCA). The objective of our study was to review the natural history of KD and ASCA using our single-center experience in diagnosing and managing KD and ASCA. METHODS: A retrospective review of the Yale radiological database from January 1999 to December 2016 was performed. Only patients with KD/ASCA and a computed tomography (CT) scan of the chest were selected for review. The primary goal was to examine the natural history of KD and ASCA and the secondary goals were to review the management and outcomes of those patients treated for KD and ASCA. RESULTS: There were 75 patients with KD/ASCA identified, with a mean age of 63 ± 19 years; 49 were female (65%). On CT scans, left- and right-sided aortas were present in 47 (63%) and 28 (37%) patients. A right ASCA or a left ASCA were present in 47 (63%) and 28 (37%) patients. Six patients were symptomatic on presentation. Symptoms included dysphagia, chest or back pain, and emboli to the fingers. The mean KD diameter was 21.8 ± 6.0 mm and the distance to the opposite aortic wall (DAW) was 48.3 ± 10.8 mm. Sixty-six patients were followed for a mean of 31.7 ± 32.5 months. One patient ruptured without repair. Nine patients underwent operative intervention, including eight open and one endovascular repair. Complications from operative intervention included ischemic stroke with hemorrhagic transformation, deep vein thrombosis and pneumonia. The mean growth rate for KD and DAW was 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year, respectively. On multivariable regression analysis, hypertension was a predictor of growth of DAW (P = .03). CONCLUSIONS: KD is uncommon and shows a female predominance. The diverticulum grows, albeit slowly (KD and DAW growth rates of 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year). Most patients are asymptomatic, but dysphagia, chest/back pain, and distal emboli may occur. Rupture is rare. Symptomatic patients should be operated. Asymptomatic patients can be followed with serial CT scans.

Cine-Computed Tomography for the Evaluation of Prosthetic Heart Valve Function.

BACKGROUND: After aortic valve replacement (AVR), suspected prosthetic valve dysfunction (mechanical or biological) may arise based on echocardiographic transvalvular velocities and gradients, leading to reoperative surgical intervention being considered. Our experience has found that 4-dimensional (space and time) image reconstruction of ECG-gated computed tomography, termed cine-CT, may be helpful in such cases. We review and illustrate our experience. METHODS: Twenty-seven AVR patients operated previously by a single surgeon (who performs >100 AVRs/year) were referred for repeat evaluation of suspected aortic stenosis (AS) based on elevated transvalvular velocities and gradients. The patients were fully evaluated by cine-CT. RESULTS: In all but 2 cases, the cine-CT strikingly and visually confirmed normal leaflet function and excursion, with no valve thrombosis, restriction by pannus, or obstruction by clot. In only 2 cases did cine-CT reveal decreased mechanical valve leaflet excursion. Repeat surgery was required in only 1 case while all other patients continued clinically without cardiac events. CONCLUSIONS: Echocardiography is an extraordinarily useful tool for the evaluation of prosthetic valve function. Increased pressure recovery beyond the valve and other factors may occasionally lead to exaggerated gradients. Cine-CT is emerging as an extremely valuable tool for further evaluation of suspected prosthetic valve AS. Our experience has been extremely helpful, as is shown in the dramatically reassuring images.

Fate of preserved bicuspid valves at time of ascending aortic aneurysmectomy.

BACKGROUND: The fate of the spared bicuspid aortic valve in patients undergoing ascending aortic aneurysm surgery is relatively unknown. Our institutional policy has been to replace all aortic valves with significant abnormalities, as evidenced by intraoperative transesophageal echocardiography or direct visual inspection. In this study, we elaborate our experience regarding the long-term fate of preserved bicuspid aortic valves after ascending aortic aneurysm extirpation. MATERIALS AND METHODS: From 2000 to 2018, 407 consecutive ascending aortic aneurysm patients with concomitant bicuspid aortic valves underwent surgery by a single surgeon at our institution. Among these, 23 (5.65%) patients did not have their valve replaced, forming the study group. Postoperative and preoperative echocardiograms were compared to determine changes in valve function. RESULTS: Follow-up was complete in 100% of patients. The average time between preoperative and postoperative echocardiograms was 4.50 ± 4.09 years (0.19-15.63). Aortic stenosis or regurgitation changed from none to mild in 5 (21.7%) of patients, with an average echocardiographic interval follow-up of 3.08 years, and from none to severe in 2 (8.7%), with an interval of 11.7 years. One patient required reoperation, including aortic valve replacement, during follow-up. CONCLUSION: Bicuspid aortic valves free of aortic stenosis or insufficiency before surgery and "healthy" appearing at surgery can safely be preserved.

Routine anterior spinal artery visualization prior to descending and thoracoabdominal aneurysm repair: High detection success.

BACKGROUND: Paraplegia is adevastating complication of open descending (DTAA) and thoracoabdominal aortic aneurysm (TAAA) repair. Despite major advances in imaging and surgical techniques, paraplegia continues to be problematic. We present our experience with routine application of enhanced imaging techniques to detect the anterior spinal artery (ASA) before DTAA and TAAA repair. METHODS: We retrospectively reviewed 177 patients with DTAA and TAAA who underwent imaging to detect the ASA before open surgical repair. High definition CT angiography (CTA) and dual energy CT scanning (DECT) were our modalities of choice with angiography used earlier and magnetic resonance angiography (MRA) used when CT was contraindicated. Descriptive statistics and χ2 analyses were conducted. RESULTS: The imaging protocol successfully detected the level of the ASA in 132 (74.5%) patients, utilizing CTA in 67, DECT in 28, spinal angiography in 31, and MRA in 6. Cross sectional modalities with advanced visualization technique (CT, DECT, and MRA) were more successful at detecting the ASA than angiography (80.72%, 82.35%, 75% vs 59.62%, respectively, P = .04). Concerted efforts were made not to leave the operating room without continuity of the ASA with the circulation (via limited resection, beveled anastomosis, or reimplantation). Transient lower extremity weakness was observed in 11 (6.2%) patients, and permanent paraplegia in 2 (1.12%) patients. CONCLUSION: Modern imaging technology provides multiple methodologies highly successful at detecting the ASA. The ASA can then be preserved intraoperatively, contributing to low paraplegia rates. We strongly recommend routine application of this technology to arm the surgeon with precise information about the specific patient's spinal cord blood supply.

Diabetes Mellitus: Is It Protective against Aneurysm? A Narrative Review.

OBJECTIVES: In the course of extensive clinical aortic surgery, we noticed that the aorta was quite thick and fibrotic in diabetic patients. We thought the diabetic aortic aorta might be inimitable to aortic dissection. On this basis, we set out to review information in the literature regarding aortic growth and dissection in diabetic patients. METHODS: We used a 2-step search approach to the available literature on diabetes and aneurysm. Firstly, databases including PubMed, Cochrane, Embase and TRIP were searched. Secondly, relevant studies were identified through secondary sources including references of initially selected articles. We address the relationship between diabetes and the incidence, prevalence, growth, mortality and rupture of an aneurysm. RESULTS: Diabetes is thought to exert a protective role in both thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Diabetics were shown to have a slower aneurysm growth rate, lower rupture rate, delayed (> 65 years) age of rupture, decreased rate of mortality from an aneurysm and a decreased length of hospital stay. There was also noted a decreased rate of incidence and prevalence of TAA and AAA in diabetics, smaller aneurysm diameter, reduction in matrix metalloproteinases and an increased aortic wall stress in diabetics. Antidiabetic agents like metformin, thiazolidinediones and dipeptidyl peptidase-4 inhibitors may protect against an aneurysm. CONCLUSION: Our literature review provides strong (but often circumstantial) evidence that diabetic patients exhibit slower growth of aortic aneurysms and a lower rate of aortic dissection. Furthermore, clinical and experimental studies indicate that common antidiabetic medications on their own inhibit growth of aortic aneurysms. These findings indicate a paradoxically beneficial effect of the otherwise highly detrimental diabetic state.

Antithrombotic Therapy after Bioprosthetic Aortic Valve Replacement: A Therapeutic Morass.

Valvular heart disease is a common pathologic condition that affects 6 million people in the United States and more than 100 million worldwide. The most common valvular disorder is aortic stenosis. Current American and European guidelines recommend surgical management for symptomatic aortic stenosis with low risk of perioperative complications and endovascular intervention for high-risk patients with multiple comorbidities. Considering the increasing volume of aortic valve replacement (AVR) with biological valves, it is very important to select the appropriate anticoagulant after surgical AVR. In this article, we review the impact of anticoagulation on immediate and remote complications after AVR.

Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size Threshold for Intervention.

BACKGROUND: Multiple studies have quantified the relationship between aortic size and risk of dissection. However, these studies estimated the risk of dissection without accounting for any increase in aortic size from the dissection process itself. OBJECTIVES: This study aims to compare aortic size before and after dissection and to evaluate the change in size consequent to the dissection itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with aortic dissection and incidental imaging studies prior to dissection were identified and compared to a control group of aneurysm patients (n = 205). The average time between measurement at and prior to dissection was 1.7 ± 1.9 years (1.9 ± 2.0 years mean inter-image time in the control group). A multivariate regression model controlling for growth rate, age, and gender was created to estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic sizes at and prior to dissection were 54.2 ± 7.0 and 45.1 ± 5.7 mm for the ascending aorta, and 47.1 ± 13.8 and 39.5 ± 13.1 mm for the descending aorta, respectively. The multivariable analysis revealed a significant impact of the dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS: The aortic diameter increases substantially due to aortic dissection itself and, thus, aortas are being dissected at clinically meaningfully smaller sizes than natural history analyses have previously suggested. These findings have important implications regarding the size at which the risk of dissection is increased.

Pilot study exploring artificial intelligence for facial-image-based diagnosis of Marfan syndrome.

Background: Marfan Syndrome (MFS), a genetic disorder impacting connective tissue, manifests in a wide array of phenotypes which can affect numerous bodily systems, especially the thoracic aorta. The syndrome often presents distinct facial features that potentially allow for diagnostic clinical recognition. Herein, we explore the potential of Artificial Intelligence (AI) in diagnosing Marfan syndrome from ordinary facial images, as assessed by overall accuracy, F1 score, and area under the ROC curve. Methods: This study explores the utilization of Convolutional Neural Networks (CNN) for MFS identification through facial images, offering a novel, non-invasive, automated, and computerized diagnostic approach. The research examines the accuracy of Neural Networks in the diagnosis of Marfan Disease from ordinary on-line facial images. The model was trained on 80 % of 672 facial images (182 Marfan and 490 control). The other 20 % of images were used as the test set. Results: Overall accuracy was 98.5 % (0 % false positive, 2 % false negative). F1 score was 97 % for Marfan facies and 99 % for non-Marfan facies. Area under the ROC curve was 100 %. Conclusion: An Artificial Intelligence (AI) program was able to distinguish Marfan from non-Marfan facial images (from ordinary on-line photographs) with an extremely high degree of accuracy. Clinical usefulness of this program is anticipated. However, due to the limited and preliminary nature of this work, this should be viewed as only a pilot study.

Midterm follow-up of composite graft replacement of the aortic root (30-year experience)-remarkably safe, effective, and durable.

Objectives: Contemporary operative choices for aortic root disease include aortic root replacement (ARR) and a variety of valve-sparing and aortic root-repair procedures. We evaluate ultra-long-term outcomes of ARR, focusing on survival, freedom from late reoperation, and adverse events. Methods: Prospectively kept records were used to accomplish long-term follow-up of patients who underwent ARR (4-pronged Yale survival assessment paradigm). Results: Between 1990 and 2020, 564 patients underwent ARR (mean 56 years, 84% male). A modified Cabrol procedure (Dacron coronary graft) was employed in 9.0% (51/564) and concomitant coronary artery bypass grafting in 9.4% (53/564). There were 12.8% (72/564) urgent/emergent and 7.4% (42/564) redo procedures. Operative mortality occurred in 12 patients (2.1%) overall, or 1.4% (8/554) of nondissection and 1.3% (6/468) of elective first-time operations. Six of the 12 deaths presented with acute type A dissection, urgent operation, or reoperative states. Operative mortality dropped to 0.6% during the past 10 years. In total, 11 patients developed endocarditis. Stroke occurred in 11 of 564 patients (2.0%), 4 of whom had presented with type A dissection. Late events included bleeding in 2.8% (16/564), thromboembolism in 1.4% (8/564), and reoperation of the root in 5 of 564 (0.9%) at 15 years and more distal aortic segments in 16/564 (2.8%). Survival was no different from age/sex-matched controls. Conclusions: This ultra-long-term experience finds ARR to be extraordinarily safe, effective, and durable, with minimal long-term bleeding, thromboembolism, or graft failure. This experience provides a standard of durability for ARR against which ultra-long-term outcomes with alternate procedures (valve-sparing, Ross, other) may be compared.

Somatic Variants Acquired Later in Life Associated with Thoracic Aortic Aneurysms: JAK2 V617F.

The JAK2 V617F somatic variant is a well-known driver of myeloproliferative neoplasms (MPN) associated with an increased risk for athero-thrombotic cardiovascular disease. Recent studies have demonstrated its role in the development of thoracic aortic aneurysm (TAA). However, limited clinical information and level of JAK2 V617F burden have been provided for a comprehensive evaluation of potential confounders. A retrospective genotype-first study was conducted to identify carriers of the JAK2 V617F variant from an internal exome sequencing database in Yale DNA Diagnostics Lab. Additionally, the overall incidence of somatic variants in the JAK2 gene across various tissue types in the healthy population was carried out based on reanalysis of SomaMutDB and data from the UK Biobank (UKBB) cohort to compare our dataset to the population prevalence of the variant. In our database of 12,439 exomes, 594 (4.8%) were found to have a thoracic aortic aneurysm (TAA), and 12 (0.049%) were found to have a JAK2 V617F variant. Among the 12 JAK2 V617F variant carriers, five had a TAA (42%), among whom four had an ascending TAA and one had a descending TAA, with a variant allele fraction ranging from 11.2% to 20%. Among these five patients, 60% were female, and average age at diagnosis was 70 (49-79). The mean ascending aneurysm size was 5.05 cm (range 4.6-5.5 cm), and four patients had undergone surgical aortic replacement or repair. UKBB data revealed a positive correlation between the JAK2 V617F somatic variant and aortic valve disease (effect size 0.0086, p = 0.85) and TAA (effect size = 0.004, p = 0.92), although not statistically significant. An unexpectedly high prevalence of TAA in our dataset (5/594, 0.84%) is greater than the prevalence reported before for the general population, supporting its association with TAA. JAK2 V617F may contribute a meaningful proportion of otherwise unexplained aneurysm patients. Additionally, it may imply a potential JAK2-specific disease mechanism in the developmental of TAA, which suggests a possible target of therapy that warrants further investigation.

Patient-specific ascending aortic intervention criteria.

OBJECTIVES: Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area and aneurysm location (root versus ascending). METHODS: Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analysed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age and body surface area, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with 'hinge points' of steep risk, constructed separately for the aortic root and mid-ascending aorta. RESULTS: A total of 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root and z = 5 for the mid-ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75-year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented, which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size. CONCLUSIONS: This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient.

Nonsize Criteria for Surgical Intervention on the Ascending Thoracic Aorta.

For decades, aortic surgery has relied on size criteria for intervention on the ascending aorta. While diameter has served well, diameter alone falls short of an ideal criterion. Herein, we examine the potential application of other, nondiameter criteria in aortic decision-making. These findings are summarized in this review. We have conducted multiple investigations of specific alternate nonsize criteria by leveraging our extensive database, which includes complete, verified anatomic, clinical, and mortality data on 2,501 patients with thoracic aortic aneurysm (TAA) and dissections (198 Type A, 201 Type B, and 2102 TAAs). We examined 14 potential intervention criteria. Each substudy had its own specific methodology, reported individually in the literature. The overall findings of these studies are presented here, with a special emphasis on how the findings can be incorporated into enhanced aortic decision-making-above and beyond sheer diameter. The following nondiameter criteria have been found useful in decision-making regarding surgical intervention. (1) Pain: In the absence of other specific cause, substernal chest pain mandates surgery. Well-developed afferent neural pathways carry warning signals to the brain. (2) Aortic length/tortuosity: Length is emerging as a mildly better predictor of impending events than diameter. (3) Genes: Specific genetic aberrations provide a powerful predictor of aortic behavior; malignant genetic variants obligate earlier surgery. (4) Family history: Aortic events closely follow those in relatives with a threefold increase in likelihood of aortic dissection for other family members once an index family dissection has occurred. (5) Bicuspid aortic valve: Previously thought to increase aortic risk (as a "Marfan light" situation), current data show that bicuspid valve is not a predictor of higher risk. (6) Diabetes actually protects against aortic events, via mural thickening and fibrosis. (7) Biomarkers: A specialized "RNA signature test" identifies aneurysm-bearing patients in the general population and promises to predict impending dissection. (8) Aortic stress: Blood pressure (BP) elevation from anxiety/exertion precipitates dissection, especially with high-intensity weightlifting. (9) Root dilatation imposes higher dissection risk than supracoronary ascending aneurysm. (10) Inflammation on positron emission tomography (PET) imaging implies high rupture risk and merits surgical intervention. (11) A KIF6 p.Trp719Arg variant elevates aortic dissection risk nearly two-fold. (12) Female sex confers some increased risk, which can be largely accommodated by using body-size-based nomograms (especially height nomograms). (13) Fluoroquinolones predispose to catastrophic dissection events and should be avoided rigorously in aneurysm patients. (14) Advancing age makes the aorta more vulnerable, increasing likelihood of dissection. In conclusion, nondiameter criteria can beneficially be brought to bear on the decision to observe or operate on specific TAA.