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.

"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.

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.

Natural history and management of splanchnic artery aneurysms in a single tertiary referral center.

OBJECTIVE: Splanchnic artery aneurysms (SAAs) are rare, and little is known about their natural history and management. We reviewed our single-center experience in managing this population of patients. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with an SAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Our primary outcomes included aneurysm growth rate and risk of rupture in those patients managed nonoperatively and morbidity and mortality of those SAA patients who underwent operative intervention. RESULTS: There were 122 patients with 138 SAAs identified; 77 were male (62%), with a mean age of 66 years (range, 25-94 years). On computed tomography, 56 (45%) had previously diagnosed or concomitant aneurysms elsewhere. Of the patients managed nonoperatively, 101 patients (79%) had 108 SAAs; in the operative intervention group, 25 (21%) patients had 30 SAAs. The mean overall vessel diameter was 1.76 ± 0.83 cm. The diameter of observed and operatively repaired SAAs was 1.58 ± 0.56 cm and 2.41 ± 1.23 cm, respectively (P = .00001). Mean follow-up was 50 ± 42 months for nonoperative management without any adverse events related to SAA, including 10 patients with SAA >2.0 cm. The mean observed growth rate for SAA was 0.064 ± 0.18 cm/y. All symptomatic patients who presented with severe abdominal pain (n = 11 [44%]) underwent operative intervention. Five patients presented with a ruptured SAA (3.6%; range, 2.3-5.0 cm); all of them except one underwent operative intervention. Other indications for repair included large size in seven, rapid growth in two, other open abdominal surgical procedures in two, multiple aneurysms in one, and desire to pursue fertility treatment in one. Operative repair included 14 (56%) endovascular embolizations and 11 (44%) open abdominal operations. After endovascular embolization, two patients underwent abdominal operation for hemorrhage and splenectomy. Open repairs included bypasses in six, splenectomy in two, resection in two, and plication in one. Two patients had postoperative acute kidney injury that resolved and one died of multisystem organ failure. One bypass occluded without sequelae. On multivariable regression analysis, female sex (P = .02) was associated with faster growth rate, and a history of smoking (P = .04) was associated with slower growth rate. CONCLUSIONS: It seems reasonable to observe asymptomatic patients with an SAA <2.0 cm because of the slow growth rate (0.064 ± 0.18 cm/y) and benign behavior. When intervention is needed, both open and endovascular options should be considered.

Natural history and management of renal artery aneurysms in a single tertiary referral center.

OBJECTIVE: Although renal artery aneurysms (RAAs) are uncommon, several large reports have been published indicating their benign natural history. The objective of our study was to review our single-center experience managing this disease entity. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with RAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. RESULTS: There were 241 patients with 259 RAAs identified, with a mean age of 69 years (range, 35-100 years); 147 were female (61%). On computed tomography, aneurysms were solitary and right sided in 224 (86%) and 159 (61%), respectively; 64 (27%) patients had aneurysms elsewhere. The breakdown of RAAs by location was as follows: renal bifurcation in 84 (32%), renal pelvis in 77 (30%), distal renal artery in 58 (22%), mid renal artery in 34 (13%), and proximal renal artery in 6 (2%). Five patients had symptoms that were attributed to the RAA and underwent operative repair; all others were observed without an operation. Symptoms in the operative repair group included flank pain in four and uncontrolled hypertension in one. The mean overall diameter of the RAAs was 1.22 ± 0.49 cm. The diameter of operatively repaired and observed RAAs was 1.84 ± 0.55 cm and 1.21 ± 0.48 cm, respectively (P = .002). Operative repair included four coil embolizations and one open resection. There were no renal function changes in any of these patients after operation and no other complications. Mean follow-up was 41 ± 35 months for patients in the group that was observed; 18 of these RAAs were >2 cm, and none ruptured. On multivariable regression analysis, female sex (P = .0001), smoking history (P = .00007), left-sided RAA (P = .03), and main renal artery location (P = .03) were inversely related to growth, whereas a history of hypertension was directly related to growth rate (P = .01). The mean growth rate for RAAs was 0.017 ± 0.052 cm/y. CONCLUSIONS: RAAs tend to have a benign natural history. Although previous reports have not identified any factors that contribute to RAA growth, we observed that RAA location, sex, smoking history, and hypertension may have an impact on growth rates. No ruptures were observed. Operative repair at our institution was rare, with no morbidity or mortality. Observation of RAAs over time seems feasible in the asymptomatic patient with a small RAA.

Natural history of aneurysmal aortic arch branch vessels in a single tertiary referral center.

OBJECTIVE: Little is known about the natural history and management of aneurysmal aortic arch branch vessels (AABVs). The objectives of this study were to assess the natural history of aneurysmal AABVs and to examine the outcomes of operative intervention. METHODS: A retrospective review of the Yale radiologic database from 1999 to 2016 was performed. Only those patients with an aneurysmal AABV and a computed tomography scan were selected for review. Patients' demographics, aneurysm characteristics, management, and follow-up information were collected. RESULTS: There were 105 patients with 147 aneurysmal AABVs; 76 were male (72%), with a mean age of 70 years (range, 17-93 years). We identified 63 innominate, 50 left subclavian, 30 right subclavian, and 4 common carotid artery aneurysms. On computed tomography, 65 (62%) had aortic aneurysms and six (6%) had suffered an aortic dissection. Most were asymptomatic (104 [99%]); one had chest pain and an enlarging swollen mass. Twelve (11%) patients underwent operative repair (OR) for 12 aneurysmal AABVs because of symptoms, growth, or concomitant aortic operations; 93 (89%) were observed in the no operative repair (NOR) group with cross-sectional imaging. The overall mean vessel diameter was 2.08 ± 0.68 cm. The mean diameters in the OR and NOR groups were 3.32 ± 1.24 cm and 1.97 ± 0.46 cm, respectively (P = .002). OR included nine bypasses with resection, two stent grafts, and one resection without reconstruction. Two patients developed postoperative hemorrhage requiring re-exploration, one patient developed stent thrombosis, and one patient required pseudoaneurysm repair 20 years after index operation. Mean follow-up was 52 ± 51 months for the NOR group, with no ruptures or emboli. The growth rate was 0.04 ± 0.10 cm/y. On multivariable regression analysis, a descending aortic aneurysm (P = .041) and a left subclavian artery aneurysm (P = .016) were associated with higher growth rates, whereas height was associated with a lower growth rate (P = .001). CONCLUSIONS: Aneurysmal AABVs tend to have a benign natural history with slow growth rates and low rates of complications, including rupture and embolization. We recommend expectant observational management for small, incidentally detected aneurysms.

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.

Body Weight and Suicidal Behavior in Adolescent Females: The Role of Self-Perceptions.

BACKGROUND: Suicide is the third leading cause of death among adolescents and recent data indicate that the suicide rate, particularly for young girls, is increasing. Excess body weight among adolescents has also been documented widely over the last two decades and is considered one of the most pressing public health concerns today. Previous literature has examined the relationship between actual body weight and suicidal behavior, but there is little evidence on self-perception of weight and suicidal behaviors. AIM OF THE STUDY: This study examines the relationship between body weight and suicidal behaviors using a rich longitudinal data set of a large nationally-representative sample of female adolescents to account for a number of confounding factors. The study explores the relationship, not only between actual weight status and suicidal behaviors, but also between self-perception of weight and suicidal behaviors. METHOD: Using data from a nationally-representative sample of adolescents in the United States, the study ascertains the effect of body weight status on suicidal behaviors by estimating endogeneity-corrected models including school-level fixed effects to account for bi-directionality and unobserved confounders. Actual body weight status was calculated using interviewer-measured height and weight. The study also used a measure of self-perceived weight status to compare how actual versus self-perceived weight status affects suicidal behavior. Thinking about committing suicide and attempting to commit suicide in the past 12 months were utilized as dichotomous measures of suicidal behaviors. Potential mediators between suicidal behaviors and weight status such as family history of suicide, participation in risky health behaviors and parental characteristics were also controlled for in the analysis. The analytical sample consists of 5,430 adolescent females aged 11 to 18. RESULTS: The results suggest that both self-perceived and measured weight status (overweight or obese) increase a female adolescent's probability of suicidal ideation, with self-perceived weight status causing a larger increase in suicidal ideation. There is some evidence that body weight status affects suicide attempts, but these results are much less robust. Finally, endogeneity bias is shown to be of concern in all estimates, and failing to account for this bias is likely to understate any estimated effect. IMPLICATIONS FOR HEALTH POLICY: The results have important implications for the design of public health programs to prevent adolescent suicide, especially among female adolescents. Understanding the mechanisms through which adolescents are motivated to take such dire actions will help to allocate resources into the treatment areas which are most effective in stemming the rise of suicidal behaviors. This study identifies one key factor, self-perception of weight, which may be an avenue for mental health care providers to continue exploring. IMPLICATIONS FOR FUTURE RESEARCH: Further research on this topic could include not only studying the impact of body weight on suicidal behaviors, but also examining the relationships between body weight and other important mental health outcomes such as psychological distress and major depressive episodes.

Aortic Size Distribution in the General Population: Explaining the Size Paradox in Aortic Dissection.

BACKGROUND: Current guidelines recommend a diameter of 5-5.5 cm as the threshold for surgery on the ascending aorta. However, a study from the International Registry of Acute Aortic Dissection showed that nearly 60% occurred at <5.5 cm (the 'aortic size paradox')--leading to a debate whether the size threshold should be lowered. However, the study showing dissection at small size had no knowledge of the population at risk. Herein, we aim to calculate the relative risk of aortic dissection at sizes<5.5 cm by analyzing both the number of occurring dissections (numerator) and the population at risk at each aortic size (denominator). METHODS: Using a publicly available database of 3,573 multiethnic subjects (46% male, mean age 60.7 years) from the general population, we plotted a distribution curve of ascending aortic size (by magnetic resonance imaging). The relative risk of aortic dissection was calculated by dividing the proportion of dissections occurring at each size (numerator) by the proportion of aortas of that same size in the general population (denominator). RESULTS: The mean ascending aortic diameter of the reference population was 3.2 cm (±0.4 cm). The largest diameter was 4.9 cm in women and 5.0 cm in men. The proportion of subjects with an aorta <3.5 cm was 79.2%, that of subjects with 3.5-3.9 cm was 18.0%, that of subjects with 4.0-4.4 cm was 2.6%, and that of subjects with ≥4.5 cm was 0.22%. The relative risk of dissection in those categories was found to be 0.055, 2.5, 4.9, and 346.8, respectively. Patients with an aorta≥4.5 cm were 6,305 times more likely to suffer aortic dissection than those with an aorta<3.5 cm. CONCLUSIONS: The normal aorta is deceptively small, most commonly <3.5 cm. The aortic size paradox is a byproduct of the very large number of patients in small size ranges. This study fully supports current recommendations for surgical intervention at 5-5.5 cm.

How Do Smokers Respond to Cigarette Taxes? Evidence from China's Cigarette Industry.

This paper examines how Chinese smokers respond to tax-driven cigarette price increases by estimating a discrete choice model of demand for differentiated products, using annual nationwide brand-level cigarette sales data in China from 2005 to 2010. We allow for substitution between different cigarette brands and also incorporate key features of rational addiction theory into the model. Results show that the average own-price elasticity of demand for cigarettes at the brand level is -0.807, and the overall price elasticity of cigarettes at the market level is -0.488 in China. We find tax-induced substitution toward low-price cigarettes as well as high-tar cigarettes and that tax hikes encourage within-class substitution more than across-class substitution. These results have important policy implications for the potential effects of cigarette taxation. Copyright © 2014 John Wiley & Sons, Ltd.

Urban-rural disparities in child nutrition-related health outcomes in China: The role of hukou policy.

BACKGROUND: Hukou is the household registration system in China that determines eligibility for various welfare benefits, such as health care, education, housing, and employment. The hukou system may lead to nutritional and health disparities in China. We aim at examining the role of the hukou system in affecting urban-rural disparities in child nutrition, and disentangling the institutional effect of hukou from the effect of urban/rural residence on child nutrition-related health outcomes. METHODS: This study uses data from the China Health and Nutrition Survey 1993-2009 with a sample of 9616 children under the age of 18. We compute height-for-age z-score and weight-for-age z-score for children. We use both descriptive statistics and multiple regression techniques to study the levels and significance of the association between child nutrition-related health outcomes and hukou type. RESULTS: Children with urban hukou have 0.25 (P < 0.01) higher height z-scores and 0.15 (P < 0.01) higher weight z-scores than children with rural hukou, and this difference by urban vs. rural hukou status is larger than the difference in height and weight (0.23 and 0.09, respectively) by urban vs. rural residence. Controlling for place of residence, children with urban hukou had 0.18 higher height z-scores and 0.17 (P < 0.01) higher weight z-scores than children with rural hukou. CONCLUSIONS: The hukou system exacerbates urban-rural disparities in child nutrition-related health outcomes independent of the well-known disparity stemming from urban-rural residence. Fortunately, however, child health disparities due to hukou have been declining since 2000.

Identifying health insurance predictors and the main reported reasons for being uninsured among US immigrants by legal authorization status.

This study identifies differences in health insurance predictors and investigates the main reported reasons for lacking health insurance coverage between short-stayed (≤ 10 years) and long-stayed (>10 years) US immigrant adults to parse the possible consequences of the Affordable Care Act among immigrants by length of stay and documentation status. Foreign-born adults (18-64 years of age) from the 2009 California Health Interview Survey are the study population. Health insurance coverage predictors and the main reasons for being uninsured are compared across cohorts and by documentation status. A logistic-regression two-part multivariate model is used to adjust for confounding factors. The analyses determine that legal status is a strong health insurance predictor, particularly among long-stayed undocumented immigrants. Immigration status is the main reported reason for lacking health insurance. Although long-stayed documented immigrants are likely to benefit from the Affordable Care Act implementation, undocumented immigrants and short-stayed documented immigrants may encounter difficulties getting health insurance coverage.

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.

Big and beautiful? Evidence of racial differences in the perceived attractiveness of obese females.

This paper investigates the relationships between body weight, race, and attractiveness in appearance and personality among adolescents. We study a sample of 5947 (non-Hispanic) white and black girls age 12 to 18 who were interviewed by a group of 338 interviewers. We find that overweight and obese white female adolescents are, respectively, 23% and 40% less likely, on average, to be perceived as physically attractive compared to normal-weight white girls. The physical appearance penalties are significantly smaller for overweight and obese black girls compared to white girls. These findings suggest that being overweight or obese is costly due to its negative impact on inner and outer perceived beauty, providing an explanation for the observed stigmatization of overweight and obesity among women in labor and relationship markets. The smaller beauty penalties for black girls above the normal-weight range suggest that the range of body sizes considered attractive may be wider for black females.

KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection.

BACKGROUND: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. METHODS: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. RESULTS: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). CONCLUSIONS: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable "non-size" criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).

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.

'Bovine' aortic arch - a marker for thoracic aortic disease.

OBJECTIVES: Very few studies have addressed the clinical significance of 'bovine' aortic arch (BA). We sought to determine whether BA is associated with thoracic aortic disease, including thoracic aortic aneurysm, aortic dissection, aortic rupture, and accelerated aortic growth rate. METHODS: We retrospectively reviewed CT and/or MRI scans of 612 patients with thoracic aortic disease and 844 patients without thoracic aortic disease to determine BA prevalence. In patients with thoracic aortic disease, we reviewed hospital records to determine growth rate, prevalence of dissection and rupture, and accuracy of radiology reports in citing BA. RESULTS: 26.3% of the patients with thoracic aortic disease had concomitant BA, compared to 16.4% of the patients without thoracic aortic disease (p < 0.001). There was no association between BA and prevalence of dissection or rupture (p = 0.38 and p = 0.56, respectively). The aortic expansion rate was 0.29 cm/year in the BA group and 0.09 cm/year in the non-BA group (p = 0.004). Radiology reports cited BA in only 16.1% of the affected patients. CONCLUSIONS: (1) BA is significantly more common in patients with thoracic aortic disease than in the general population. (2) Aortas expand more rapidly in the setting of BA. (3) Radiology reports often overlook BA. (4) BA should not be considered a 'normal' anatomic variant.

Direct health care insurer and out-of-pocket expenditures of inflammatory bowel disease: evidence from a US national survey.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, debilitating conditions that can have important economic and clinical implications. AIM: To quantify individual and national estimates of the health care and patient out-of-pocket (OOP) costs of CD and UC. METHODS: In a retrospective study using 1996 to 2009 data from the Medical Expenditure Panel Survey, individuals' self-reported health conditions were mapped to International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Individuals with a code of 555.x (CD) or 556.x (UC) were identified. Health care services and costs included prescriptions and inpatient, outpatient, emergency room, office, and home health services. OOP costs were the portion of individuals' total payments for health care services. RESULTS: There were 358 individuals with CD (mean age 49.0 years; 55 % female), 198 individuals with UC (mean age 47.1 years; 64 % female), and 206,993 individuals without inflammatory bowel disease (IBD) (mean age 48.2 years; 58 % female). Annual per capita health insurer and OOP costs for individuals with CD were greater than those without IBD ($9,526 versus $3,781, p < 0.001 and $1,603 versus $866, p < 0.001, respectively). Health insurer and OOP costs were greater for UC compared with those without IBD ($6,443 versus $3,781, p < 0.001 and $1,263 versus $866, p < 0.001, respectively). US national aggregate annual estimates of health insurer, OOP, and total direct costs secondary to CD are $2.04 billion, $0.26 billion, and $2.29 billion, respectively. Aggregate health insurer, OOP, and total direct costs attributable to UC are $0.53 billion, $0.07 billion, and $0.61 billion, respectively. CONCLUSIONS: The direct costs associated with CD and UC are substantial. The extent to which appropriate diagnosis and treatment reduces the total health care costs for individuals with CD or UC should be examined.

Patient preferences for mitral valve regurgitation treatment: a discrete choice experiment.

INTRODUCTION: This study aimed to quantify patients' preferences for benefits and risks associated with treating degenerative mitral regurgitation (DMR) via open heart surgical repair versus a beating heart surgical approach. METHODS: A D-efficient main effects discrete choice experiment (DCE) survey with 10 choice tasks that involved trade-offs across six attributes varying between two and four levels each (procedure invasiveness, recovery intensity, risk of disabling stroke, risk of new onset atrial fibrillation, risk of symptom reappearance and risk of reintervention) was administered online to either clinically confirmed (n = 30) or self-reported DMR (n = 88) patients recruited from either cardiovascular clinics or online clinical patient databases. The error component logit (ECL) analysis combined both patient cohorts after performing a Swait-Louviere scale test. Patient trade-offs across attributes were estimated in relation to either an open-heart surgery (OHS) treatment profile or a beating heart approach. RESULTS: Patients demonstrated clear preferences across all attributes for the beating heart treatment. 76.0% (95% CI: 68.1,83.9) of patients would prefer a 'beating heart' intervention relative to the 'open heart' approach despite the higher likelihood of symptom recurrence and reintervention. In exchange for the combined net benefits associated with a 'beating heart' treatment, on average, participants were willing to accept a maximum acceptable risk (MAR) of 34.6 percentage points (95% CI: 23.8,45.4) for increased risk of symptom reappearance or 22.6 percentage points (95% CI: 14.7,30.4) increased risk of reintervention. CONCLUSION: This study of US adults with DMR provides quantitative measures of risk tolerance for tradeoffs related to repair by a beating heart approach relative to conventional open-heart surgery (standard of care). These results may inform DMR treatment choices from regulatory agencies, payers, clinicians, and patients considering a beating heart repair or treatments with similar attributes as potential new alternatives to conventional surgery.