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 vs ascending). METHODS: Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analyzed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age, and BSA, 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: 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.

"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.

Safety of cerebrospinal fluid drainage in descending and thoracoabdominal aortic replacement surgery.

Background: Spinal cord injury (SCI) remains a significant morbidity of surgical repair of descending thoracic aortic aneurysms (DTAA) and thoracoabdominal aortic aneurysms (TAAA). We present our 17-year experience with cerebrospinal fluid drainage (CSFD) as a protective strategy during open surgical repair of descending and thoracoabdominal aortic disease. Methods: We conducted a retrospective chart review of 132 patients who underwent open surgical repair of DTAA and TAAA and dissections with concurrent use of CSFD for spinal cord protection. Information regarding survival, postoperative course, and complications related to CSFD use were extracted from electronic health records (EHR) and analyzed. Results: Mean patient age was 65.4±13.0 years, and 82 (62.1%) were male. A CSFD was successfully inserted in all patients. The mean hospital length of stay after surgery was 12.2±11.2 days, and in-hospital mortality was 7.6%. Postoperative transient paresis was observed in 5 patients (3.8%), and permanent paraplegia was seen in 4 (3.0%). CSFD related complications were reported in 25 patients (19%). Complications included persistent cerebrospinal fluid (CSF) leakage, blood-tinged CSF (with subdural hematoma reported in 3 patients) and spinal cutaneous fistula in 9 (7%), 14 (11%), and 1 (1%), respectively. Long term survival was 50.9% at 15 years. Conclusions: CSFD is associated with minor complications, without major sequalae. It is a safe practice and likely contributes innocuously to decreased SCI in patients undergoing open repair of DTAA and TAAA.

Comparison of Genes Associated with Thoracic and Abdominal Aortic Aneurysms.

Aneurysms impacting the ascending thoracic aorta and the abdominal aorta affect patient populations with distinct clinical characteristics. Through a literature review, this paper compares the genetic associations of ascending thoracic aortic aneurysm (ATAA) with abdominal aortic aneurysms (AAA). Genes related to atherosclerosis, lipid metabolism, and tumor development are associated specifically with sporadic AAA, while genes controlling extracellular matrix (ECM) structure, ECM remodeling, and tumor growth factor ß function are associated with both AAA and ATAA. Contractile element genes uniquely predispose to ATAA. Aside from known syndromic connective tissue disease and poly-aneurysmal syndromes (Marfan disease, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome), there is only limited genetic overlap between AAA and ATAA. The rapid advances in genotyping and bioinformatics will elucidate further the various pathways associated with the development of aneurysms affecting various parts of the aorta.

The natural history of aortic root aneurysms.

The aortic root has a different embryologic origin from all other segments of the human aorta, a feature that likely confers unique susceptibilities, anatomical patterns, and clinical behavior of aneurysm disease in this vital location. In this manuscript, we review the natural history of ascending aortic aneurysm, with a specific focus on the aortic root. The specific central message is that root dilatation is more malignant than ascending dilatation.

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.

Full calcium jacket: Conservative management of a traumatic aortic injury.

We describe the case of an elderly male patient who presented with a proximal descending aortic aneurysm after a motorcycle accident in 1977. We concluded that the aorta had been transected at that time. In a rather unconventional manner, the aneurysm developed a circumferential layer of calcification that provided mechanical stability and likely prevented further degeneration. We chose not to pursue surgical intervention at the late stage of his presentation. The patient has been followed up for a period of 30 years, with no change in the size and shape of the now completely calcified aneurysm.

Aortic Size at the Time of Type A and Type B Dissections.

BACKGROUND: Aortic diameter at time of dissection remains an indispensable risk-determining characteristic for prophylactic repair of thoracic aortic aneurysms. Histograms of aortic size at the time of dissection have the potential to shed more light on this relationship. METHODS: Size of the thoracic aorta at the time of dissection was determined from imaging of 407 naturally occurring, acute, flap-type ascending or descending aortic dissections treated at 1 institution (1990-2022). Histograms were constructed to depict aortic size at the time of dissection. Data were analyzed by logistic regression. RESULTS: There were 170 (69.11%) of 246 type A dissections (median, 5.07 cm; interquartile range, 4.60-5.67 cm) and 130 (80.75%) of 161 type B dissections (median, 4.2 cm; interquartile range, 3.60-4.87 cm) that occurred at diameters <5.5 cm. By unadjusted regression, factors associated with significantly increased odds of type A dissection at diameters <5.5 cm were female sex (odds ratio [OR], 2.06; P = .023), hypertension (OR, 1.82; P = .036), and smoking (OR, 1.92; P = .029). Patients with bicuspid aortic valve had significantly decreased odds of type A dissection at diameters <5.5 cm (OR, 0.3; P = .047). The recent "left shift" to 5.0 cm in the criterion for ascending aortic intervention could prevent an additional 29.3% of type A dissections. CONCLUSIONS: Aortic diameter at the time of type A dissection is consistent with the new guidelines that recommend surgical intervention at 5.0 cm. Type B dissection occurs at small sizes and cannot be prevented with a size criterion.

Bicuspid aortopathy does not require earlier surgical intervention.

OBJECTIVES: Guidelines for surgical correction of patients with ascending thoracic aortic aneurysm (ATAA) with a bicuspid aortic valve (BAV) have oscillated over the years. In this study, we outline the natural history of the ascending aorta in patients with BAV and trileaflet aortic valve (TAV) ATAA followed over time, to ascertain if their behavior differs and to determine if a different threshold for intervention is required. METHODS: Aortic diameters and long-term complications (ie, adverse aortic events) of 2428 patients (554 BAV and 1874 TAV) with ATAA before operative repair were reviewed. Growth rates, yearly complication rates, event-free survival, and risk of complications as a function of aortic size were calculated. Long-term follow-up and precise cause of death granularity was achieved via a comprehensive 6-pronged approach. RESULTS: Aortic growth rate in patients with BAV vs TAV ATAA was 0.20 and 0.17 cm/year, respectively (P = .009), with the rate increasing with increasing aortic size. Yearly adverse aortic events rates increased with ATAA size and were lower for patients with BAV. The relative risk of adverse aortic events exhibited an exponential increase with aortic diameter. Patients with BAV had a lower all-cause and ascending aorta-specific adverse aortic events hazard. Age-adjusted 10-year event-free survival was significantly better for patients with BAV, and BAV emerged as a protective factor against type A dissection, rupture, and ascending aortic death. CONCLUSIONS: The threshold for surgical repair of ascending aneurysm with BAV should not differ from that of TAV. Prophylactic surgery should be considered at 5.0 cm for patients with TAV (and BAV) at expert centers.

A machine learning approach for predicting complications in descending and thoracoabdominal aortic aneurysms.

OBJECTIVE: To use machine learning to predict rupture, dissection, and all-cause mortality for patients with descending and thoracoabdominal aortic aneurysms in an effort to improve on diameter-based surgical intervention criteria. METHODS: Retrospective data from 1083 patients with descending aortic diameters 3.0 cm or greater were collected, with a mean follow-up time of 3.52 years and an average descending diameter of 4.13 cm. Six machine learning classifiers were trained using 44 variables to predict the occurrence of dissection, rupture, or all-cause mortality within 1, 2, or 5 years of initial patient encounter for a total of 54 (6 × 3 × 3) separate classifiers. Classifier performance was measured using area under the receiver operator curve. RESULTS: Machine learning models achieved area under the receiver operator curves of 0.842 to 0.872 when predicting type B dissection, 0.847 to 0.856 when predicting type B dissection or rupture, and 0.820 to 0.845 when predicting type B dissection, rupture, or all-cause mortality. All models consistently outperformed descending aortic diameter across all end points (area under the receiver operator curve = 0.713-0.733). Feature importance inspection showed that other features beyond aortic diameter, such as a history of myocardial infarction, hypertension, and patient sex, play an important role in improving risk prediction. CONCLUSIONS: This study provides surgeons with a more accurate, machine learning-based, risk-stratification metric to predict complications for patients with descending aortic aneurysms.

Cerebrospinal Fluid Drainage for Prevention of Spinal Cord Ischemia in Thoracic Endovascular Aortic Surgery-Pros and Cons.

Thoracic endovascular aortic repair (TEVAR) carries a risk of spinal cord ischemia (SCI) which exerts a devastating impact on patient's quality of life and life expectancy. Although routine prophylactic cerebrospinal fluid (CSF) drainage is not unequivocally supported by current data, several studies have demonstrated favorable outcomes. Patients at high risk for SCI following TEVAR likely will benefit from prophylactic CSF drains. However, the intervention is not risk free, and thorough risk/benefit analysis should be individualized to each patient.

Rapid growth of thoracic aortic aneurysm: Reality or myth?

OBJECTIVES: The American Association for Thoracic Surgery 2010 guidelines stipulate that rapid growth of the aorta (>3 mm/y) is an indication for prophylactic surgical intervention. Because of the many potential sources of error in aortic measurement (including measurement variability and comparison of noncorresponding segments), we explored whether rapid aortic growth was a reality or a falsehood. METHODS: Among 2781 patients with aortic disease who were treated over 3 decades, we examined aortic growth rate in 811 patients with at least 2 aortic images taken at least 2 years apart. We identified 42 ascending and 27 descending patients with putative rapid aortic growth. A team of experienced clinicians reread the source images. RESULTS: Among the 42 ascending patients with putative rapid aortic growth, rapid growth was confirmed in 12 and refuted in 11 (19 images nonretrievable). Among the 27 descending patients, rapid growth was confirmed in 6 and refuted in 4 (17 images nonretrievable). We calculated lower, middle, and highest possible rapid growth rates by prorating positivity rates for nonretrievable scans. Lowest, middle, and highest possible rates of rapid growth were 2.7%, 4.7%, and 6.9% for ascending aorta, and 1.6%, 4.3%, and 7.3% for descending aneurysms, respectively. Middle rates are considered most accurately reflective. Of the patients with confirmed rapid growth, 3 of 4 inoperable patients succumbed to their aorta. Twenty-three patients underwent prompt surgery, with 22 survivors. For the rapidly growing aortas, operative, pathologic, and genetic findings are reported. CONCLUSIONS: Although not a falsehood, rapid growth is uncommon for the ascending and descending aorta. Many putative cases are reflective of measurement error. Attention to potential sources of measurement error is key. VIDEO ABSTRACT.

Toward standard abbreviations and acronyms for use in articles on aortic disease.

Objectives: Academic medical literature is fraught with complex article-specific acronyms and abbreviations that can impair communication and make reading arduous. Our goal is to ease frustration with bespoke, inconsistent, and variable sets of abbreviations that currently exist for common aorta-related terminology (eg, anatomy, imaging, disease, and therapy). We hope to ease reading and improve communication in the aortic sphere of cardiovascular literature. Methods: We reviewed a total of 205 published references related to aortic disease, including a systematic review of aorta-related articles in the Journal of Thoracic and Cardiovascular Surgery from the years 2020 and 2021. The array of variable definitions, abbreviations, and acronyms encountered in different papers that refer to the same terminology was striking, revealing that there were few standardized abbreviations in the aortic literature. We cataloged these terms, their associated abbreviations, and their frequency of use, and compiled a list of proposed standard abbreviations for commonly used terms that could be implemented uniformly in articles written about aortic diseases. Results: We present suggested acronyms and abbreviations for common terminology related to the aorta. It is anticipated that this standard list will evolve over time as the literature and technology of the field grows and develops. Conclusions: A proposed standard set of acronyms and abbreviations for aorta-related terminology is provided that, if found useful, could be implemented broadly in the aortic literature.