OBJECTIVE:To conduct a formal welfare analysis quantifying the economic costs of racial and ethnic disparities in dental care access among Hispanic and non-Hispanic Black, Asian, and multiracial adults relative to non-Hispanic White individuals in the United States. STUDY SETTING AND DESIGN:Cross-sectional, observational study using pooled nationally representative data from the 2014 to 2023 Medical Expenditure Panel Survey (MEPS). Two-part models were employed: generalized linear model (GLM) with log link for the probability of any dental visit and generalized linear gamma regression models with log link for modeling visit frequency, total annual expenditures, and expenditure per visit among users. DATA SOURCES:MEPS Full-Year Consolidated Data Files, 2014-2023. The final pooled cross-sectional analytic sample included 205,894 respondents aged 18 and older, representing a survey-weighted annual population of 251,029,718 US adults. Dollar figures are in constant 2023 US dollars. PRINCIPAL FINDINGS:All examined minority groups experienced lower dental care access and higher expenditure per visit compared with White individuals. Estimated aggregate annual welfare losses ranged from $8.23 to $12.93 billion for Hispanics, $6.44 to $9.84 billion for non-Hispanic Blacks, $2.82 to $4.30 billion for Asians, and $1.57 to $2.57 billion for individuals of other or multiple racial identities (total $19.06-$29.64 billion). CONCLUSIONS:Dental care disparities persist after adjusting for socioeconomic, demographic, and health characteristics, generating large aggregate welfare losses for minority communities. Addressing provider diversity, cultural competency, and structural barriers is essential to reducing these inequities.

Non‑Hispanic Black patients have higher non‑elective cesarean rates than Whites, but it is unclear how much of this gap is due to observable patient and hospital factors versus unmeasured structural influences. We analyzed 160,122 patients who were either Non-Hispanic Black or White using New York State Statewide Planning and Research Cooperative System (SPARCS) files for New York City and Long Island for the years 2018-2022. Racial group characteristics were compared using chi-square tests and the Oaxaca Blinder decomposition method was employed to decompose the racial disparity in cesarean surgery into explained and unexplained components. Cesarean rates were 37.8

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.

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).

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.

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.

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.

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.

Central MessageRecent findings in ascending aortic aneurysm disease suggest that a "left-shift" to 5.0 cm aortic size be considered for prophylactic surgical intervention. Recent findings in ascending aortic aneurysm disease suggest that a "left-shift" to 5.0 cm aortic size be considered for prophylactic surgical intervention. This Opinion paper argues for earlier intervention for aneurysms of the ascending thoracic aorta: specifically, for shifting the general criterion for intervention "leftward" on the aortic size continuum, from the current 5.5 cm to 5.0 cm. We describe 5 specific reasons for such a criterion shift. Of course, patient-specific criteria for surgical intervention need to be indexed to measures of body size, like body surface area or height. These body size corrections also accommodate for the generally smaller size of women compared with men. We have published such guides, with accompanying tables and charts. We currently favor height as the best reference frame for interpreting aortic size (Figure 1).1Zafar M.A. Li Y. Rizzo J.A. Charilaou P. Saeyeldin A. Velasquez C.A. et al.Height alone, rather than body surface area, suffices for risk estimation in ascending aortic aneurysm.J Thorac Cardiovasc Surg. 2018; 155: 1938-1950Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar We have also found aortic length (measured along a center line from the aortic annulus to the base of the innominate artery) to be an excellent predictor of upcoming adverse aortic events (dissection and rupture).2Wu J. Zafar M.A. Li Y. Saeyeldin A. Huang Y. Zhao R. et al.Ascending aortic length and risk of aortic adverse events: the neglected dimension.J Am Coll Cardiol. 2019; 74: 1883-1894Crossref PubMed Scopus (82) Google Scholar However, it is still helpful for daily practice to have a general intervention threshold size criterion in mind, which would apply to most individuals of average body size. One might think that the well known International Registry of Acute Aortic Dissection (IRAD) diagram (Figure 2)3Pape L.A. Tsai T.T. Isselbacher E.M. Oh J.K. O'gara P.T. Evangelista A. et al.Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD).Circulation. 2007; 116: 1120-1127https://doi.org/10.1161/CIRCULATIONAHA.107.702720Crossref PubMed Scopus (662) Google Scholar—showing that >50% of dissections occur before the size criterion of 5.5 cm—would be the cornerstone of our argument for earlier intervention. However, a careful analysis of this IRAD graph reveals substantial limitations, which dramatically soften its decision-making implications. In fact, the IRAD authors wisely did not recommend amending traditional intervention criteria on the basis of these findings. It is instructive to explore the IRAD graph from a population dynamics point of view, which we have done in a report dedicated to that purpose.4Paruchuri V. Salhab K.F. Kuzmik G. Gubernikoff G. Fang H. Rizzo J.A. et al.Aortic size distribution in the general population: explaining the size paradox in aortic dissection.Cardiology. 2015; 131: 265-272Crossref PubMed Scopus (80) Google Scholar It is vital to keep in mind that IRAD only "knows" the numerator value of patients who present to any of their 30 centers with aortic dissection. They do not "know" the denominator of patients living within different size ranges in those many locales. We determined the population segments living in different aortic size ranges, leveraging the Multi-Ethnic Study of Atherosclerosis (MESA) study,5Bild D.E. Bluemke D.A. Burke G.L. Detrano R. Diez Roux A.V. Folsom A.R. et al.Multi-Ethic study of atherosclerosis: objectives and design.Am J Epidemiol. 2002; 156: 871-881Crossref PubMed Scopus (2849) Google Scholar which determined aortic size in 3573 patients using magnetic resonance imaging, as part of a non–aorta-related general health study. Those of us working in the field of aortic care get inured to large aortic sizes. We forget just how small the normal ascending aorta really is. In the MESA study, the mean aortic size was 3.2 cm. The maximum aortic size—in any of those thousands of "normal" individuals was 5.0 cm. Not a single patient had an aorta >5.0 cm. So, in thousands of normal individuals, all the aortas in those thousands of normal patients could be considered "guppies" compared with the aortas that we see every day. Now, like so many physical phenomena, aortic size follows a bell curve (Figure 3). We constructed a bell curve for aortic size from the MESA data. The patients with large aortas, ≥5.5 cm, were far out on the right tail of the bell curve. The important point to realize is that, as one moves leftward on the bell curve of aortic size, the number of patients increases dramatically—exponentially, in fact. Thus, although few individuals harbor aortas >5 or 5.5 cm, many—millions in the United States alone—harbor aortas in the smaller sizes—say 4 to 4.5 cm. So, at the smaller aortic sizes, the denominator of patients potentially at risk of an aortic event becomes huge (Table 1). By taking into account the numerator of patients who have suffered an aortic dissection, and the huge denominator of patients living at those smaller aortic sizes, mathematical analysis revealed that a patient with an aorta >4.5 cm is more than 6000 times more likely to suffer an aortic dissection than those with smaller aortas. So, to save those dissecting at smaller sizes, we would need to operate on millions of individuals at very small risk from their aortic disease. The IRAD investigators were wise not to recommend clinical practice changes on the basis of their findings.Table 1Evaluation of relative risk of aortic dissection in various size ranges, taking into account the numerator (those suffering aortic dissection) and the denominator (those in the corresponding size range, thus at risk in that size range for suffering aortic dissection)Aortic diameter (ascending), cm≤3.4 cm3.5-3.9 cm4.0-4.4 cm≥4.5 cm∗Note in line 2 how dramatically the proportion of the population increases as one moves left in aortic size ranges. Note the relative risk levels for each size depicted in line 3. Note the powerful effect of aortic size in line 4 (>6000-fold). Reprinted with permission from Bild and colleagues.5Line 1Proportion of dissections from IRAD, %3Pape L.A. Tsai T.T. Isselbacher E.M. Oh J.K. O'gara P.T. Evangelista A. et al.Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD).Circulation. 2007; 116: 1120-1127https://doi.org/10.1161/CIRCULATIONAHA.107.702720Crossref PubMed Scopus (662) Google Scholar4.44.512.776.3Line 2Proportion of population from MESA, %79.218.02.60.22Line 3Relative risk (line 1/line 2)0.0550.254.9346.8Line 4Relative risk (compared with aortas ≤3.4 cm)14.5589.16305.5IRAD, International Registry of Acute Aortic Dissection; MESA, Multi-Ethnic Study of Atherosclerosis.∗ Note in line 2 how dramatically the proportion of the population increases as one moves left in aortic size ranges. Note the relative risk levels for each size depicted in line 3. Note the powerful effect of aortic size in line 4 (>6000-fold). Reprinted with permission from Bild and colleagues.5Bild D.E. Bluemke D.A. Burke G.L. Detrano R. Diez Roux A.V. Folsom A.R. et al.Multi-Ethic study of atherosclerosis: objectives and design.Am J Epidemiol. 2002; 156: 871-881Crossref PubMed Scopus (2849) Google Scholar Open table in a new tab IRAD, International Registry of Acute Aortic Dissection; MESA, Multi-Ethnic Study of Atherosclerosis. Now, we explore reasons that do favor a small "left-shift" from the general criterion of 5.5 cm toward the 5.0-cm aortic size:1.New hinge points at smaller aortic sizes. In our original analyses, done more than 2 decades ago, our hinge point curves showed only a single, distinct hinge point at 6.0 cm—at which risk of adverse aortic events rose dramatically. Those analyses were made on the basis of 230 patients. Now, in new analyses with 3500 patients, we can achieve much greater granularity of the risk curve (Figure 4). We now find 2 distinct hinge points, at 5.25 and 5.75 cm.1Zafar M.A. Li Y. Rizzo J.A. Charilaou P. Saeyeldin A. Velasquez C.A. et al.Height alone, rather than body surface area, suffices for risk estimation in ascending aortic aneurysm.J Thorac Cardiovasc Surg. 2018; 155: 1938-1950Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar To accommodate these recently identified hinge points (and, thus, prevent aortic-related death), one must move the intervention criterion leftward, to 5.0 cm.2.Abrupt increase in aortic size at the moment of aortic dissection. Several decades ago, we induced aortic dissection in the animal laboratory. We noted an instant change in the size and mechanical characteristics of the aorta occurring within a split second of the dissection process.6Morales D.L. Quin J.A. Braxton J.H. Hammond G.L. Gusberg R.J. Elefteriades J.A. Experimental confirmation of effectiveness of fenestration in acute aortic dissection.Ann Thorac Surg. 1998; 66: 1679-1683Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The Penn group pointed out the clinical significance of this in the clinical prediction of aortic events.7Rylski B. Blanke P. Beyersdorf F. Desai N.D. Milewski R.K. Siepe M. How does the ascending aorta geometry change when it dissects?.J Am Coll Cardiol. 2014; 63: 1311-1319Crossref PubMed Scopus (176) Google Scholar We as well have explored this phenomenon.8Mansour A.M. Peterss S. Zafar M.A. Rizzo J.A. Fang H. Charilou P. et al.Prevention of aortic dissections suggests a diameter shift to a lower aortic size threshold for intervention.Cardiology. 2018; 139: 139-156Crossref PubMed Scopus (65) Google Scholar By serendipity, some of our thousands of ascending aortic aneurysm patients had undergone a computed tomography scan in close temporal proximity to when their ascending aortic dissection actually occurred. This was usually in the context of lung nodules being followed with routine yearly scans. So, in a subgroup of patients (several dozen) we had available a pre- and an immediate postdissection scan. What we found (Figure 5) was that aortic size increased dramatically, by approximately 8 mm, at the moment of aortic dissection. Of course, most of the patients in our database had only a postdissection scan. This means that our previous calculations of aortic behavior were, of necessity, on the basis of the wrong scan—the postdissection scan. The real size at the moment of dissection was likely to have been approximately 8 mm smaller than on the study available to the clinician caring for the patient at the time of the dissection event. This important factor obligates a left shift in our criterion. Video 1 presents a beautiful demonstration of this phenomenon.Figure 5"Timeline" of recommended size criteria for surgical intervention on the ascending aorta for genes known to cause thoracic aortic aneurysm. Reprinted with permission from Vinholo and colleagues.10Vinholo T.F. Brownstein A.J. Ziganshin B.A. Zafar M.A. Kuivaniemi H. Body S.C. et al.Genes associated with thoracic aortic aneurysm and dissection: 2019 update and clinical implications.Aorta (Stamford). 2019; 4: 99-107Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)3.Advent of whole-exome sequencing. Heretofore, we had to place all of our ascending aortic aneurysm patients "into a single therapeutic bucket," that is, into a single pattern of medical care and surgical triage. In the year 2001, the first sequencing of the genome of a human being, that of Craig Venter, President of Celera Genomics, rocked the world.9Venter J.C. Adams M.D. Myers E.W. Li P.W. Mural R.J. Sutton C.G. et al.The sequence of the human genome.Science. 2001; 291: 1304-1351Crossref PubMed Scopus (11010) Google Scholar In the subsequent 2 decades, whole-exome sequencing has become widespread and somewhat affordable. Thus, for many of our ascending aortic aneurysm patients, we can determine the specific genetic defect that underlies their aneurysm. And, we can now place these patients into "disease-specific" categories. Each causative gene predicts disease-specific behavior and merits its own criteria for intervention (Figure 5). As several new genes are generally identified each year, we publish an updated list at regular intervals in the journal, Aorta (Stamford).10Vinholo T.F. Brownstein A.J. Ziganshin B.A. Zafar M.A. Kuivaniemi H. Body S.C. et al.Genes associated with thoracic aortic aneurysm and dissection: 2019 update and clinical implications.Aorta (Stamford). 2019; 4: 99-107Google Scholar Gene-specific information also allows us to predict not only the size, but also the general age at which dissection is likely to occur, for a specific causative gene (Figure 6).11Mariscalco G. Debiec R. Elefteriades J.A. Samani N. Murphy G.J. Systematic review of studies that have evaluated screening tests in relatives of patients affected by nonsyndromic thoracic aortic disease.J Am Heart Assoc. 2018; 7: e009302https://doi.org/10.1161/JAHA.118.009302Crossref PubMed Scopus (30) Google Scholar For many patients, these disease-specific guidelines merit a left shift to operation at smaller aortic sizes.Figure 6The characteristics at onset of aortic dissection. Age is plotted on the y-axis and aortic diameter on the x-axis. Bubbles represent specific causative genes indicated. The vertical and horizontal dimensions of the circles and ovals represent the relative standard deviations for age and aortic size, respectively.View Large Image Figure ViewerDownload Hi-res image Download (PPT)4.Safety of aortic surgery in the present era. As aortic surgical training and experience accumulate worldwide, operations on the ascending aorta have become safer and safer. At our institution, and at many other centers, the risk of death of ascending/arch replacement is only 1.9%, and the accompanying risk of stroke is only 1.4%.12Mok S.C. Ma W.G. Mansour A. Charilaou P. Chou A.S. Peterss S. et al.Twenty-five year outcomes following composite graft aortic root replacement.J Card Surg. 2017; 32: 99-109Crossref PubMed Scopus (31) Google Scholar, 13Peterss S. Charilaou P. Dumfarth J. Li Y. Bhandari R. Tranquilli M. et al.Aortic valve disease with ascending aortic aneurysm: impact of concomitant root-sparing (supracoronary) aortic replacement in nonsyndromic patients.J Thorac Cardiovasc Surg. 2016; 152: 791-798.e1https://doi.org/10.1016/j.jtcvs.2016.05.020Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 14Ziganshin B.A. Rajbanshi B.G. Tranquilli M. Fang H. Rizzo J.A. Elefteriades J.A. Straight deep hypothermic circulatory arrest for cerebral protection during aortic arch surgery: safe and effective.J Thorac Cardiovasc Surg. 2014; 148: 888-898Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar As Kim and colleagues15Kim J.B. Spotnitz M. Lindsay M.E. Isselbacher E.M. Sundt III, T.M. Risk of aortic dissection in the moderately dilated ascending aorta.J Am Coll Cardiol. 2016; 68: 1209-1219Crossref PubMed Scopus (114) Google Scholar have eloquently articulated, surgical decisions should always represent a careful balancing of benefit versus risk. With risks of aortic surgery becoming so low, this argues for a more liberal "left shift" in our intervention criteria.5.Effect of previous dissection in a family member. In a recent study,16Ma W.G. Chou A.S. Mok S.C.M. Ziganshin B.A. Charilaou P. Zafar M.A. et al.Positive family history of aortic dissection dramatically increases dissection risk in family members.Int J Cardiol. 2017; 240: 132-137Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar we showed that once a dissection has occurred in 1 family member, the likelihood of a dissection in another family member with an aneurysm increases nearly threefold. This argues for near-uniform elective, prophylactic intervention in the family member, almost regardless of aortic size. This recognition merits a "left shift" in criteria for these family members. So, for these reasons we do recommend "shifting left" with the general criterion for intervention for ascending aortic aneurysms, from the current (2010) guideline of 5.5 cm17Hiratzka L.F. Bakris G.L. Beckman J.A. Bersin R.M. Carr V.F. Casey Jr., D.E. et al.2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine.Circulation. 2010; 121: e266-e369Crossref PubMed Scopus (2155) Google Scholar toward 5.0 cm (Figure 7). Of course, the size criterion adjustments for very small or very large individuals mentioned previously need to be applied for patients far from average body sizes (either larger or smaller individuals). First, the 5 mm "left shift" we have recommended cannot fully accommodate the newly recognized approximately 8-mm abrupt increase in aortic diameter occurring at the moment of aortic dissection. Full accommodation would require a dramatic shift. We have opted to recommend a more modest shift in the correct direction, without proposing that even smaller asymptomatic aortas be operated routinely at the present time. Second, it remains to be seen whether the suggested changes save substantial lives or prove cost-effective. We do wish to mention 2 additional factors related specifically to the aortic root: (1) first, our very recent study18Kalogerakos P.D. Zafar M.A. Li Y. Mukherjee S.K. Ziganshin B.A. Rizzo J.A. et al.Root dilatation is more malignant than ascending aortic dilatation.J Am Heart Assoc. 2021; 10: e020645https://doi.org/10.1161/JAHA.120.020645Crossref PubMed Scopus (16) Google Scholar shows that dilatation in the root portion is more malignant than dilatation in the ascending aorta above the root. We recommend that separate measurement of root diameter always be made and included in the decision-making. And, (2) we wish to emphasize that there is no single, uniform method generally applied for measurement of the aortic root. In fact, the very term, "diameter," applies to circles, not to cloverleaf shapes like the aortic root. There is not even any specific meaning to the "diameter" of a cloverleaf-shaped structure. Some centers measure from commissure to sinus, others from sinus to sinus. Others use the transverse diameter in the coronal images. Our team has worked intensively on troublesome issues in aortic imaging,19Elefteriades J.A. Mukherjee S.K. Mojibian H. Discrepancies in measurement of the thoracic aorta: JACC review topic of the week.J Am Coll Cardiol. 2020; 76: 201-217https://doi.org/10.1016/j.jacc.2020.03.084Crossref PubMed Scopus (64) Google Scholar including those affecting root measurements, and we plan an additional clarifying publication in the near future. John A. Elefteriades: CoolSpine—Principal, Tissium—Consultant. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiIzZGE3YTc3NjViMDA0YzA0YmRjMTM4ODE1OTUwMWZkZSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzE0NTE5MDQ3fQ.SsdyHzhodxW76FTTufxDggNb-6dro0RiDFf03BrzQHxEkcL4e36SNGvZZUGQ56-DRjxZS30JgZJYUjG3bcZoTq3wyjQy1Fn1Uz--SrArbDPgZeZlufhL2801GyomMKPyj73YE7ELVx3htKHnb-1Xf69eq-GMrerqWUT1R8v3BoQZHirbj7nkfbpNiXUvkr7KVn8gFmG2o28AoGBRDY54vQESKA7t44eF0BmxzgKbmfFJxcrXoJ-Xe3h0_pgXH_KMPmf_rtK8f2Ys5vldSR0i3_M-jfaJoUeS16P73rIbO728wSz-WhaHVef5q6P4631R3kmUcQKuXLHhNAEVNa4s7w Download .mp4 (7.89 MB) Help with .mp4 files Video 1Superimposed images from yearly surveillance CT scans (for lung nodules) demonstrate indolent growth (approximately 1 mm per year) for multiple years, until sudden growth (approximately 7 mm) at the moment of aortic dissection. Video available at: https://www.jtcvs.org/article/S0022-5223(22)00833-9/fulltext. Download .jpg (.24 MB) Help with files Video 1Superimposed images from yearly surveillance CT scans (for lung nodules) demonstrate indolent growth (approximately 1 mm per year) for multiple years, until sudden growth (approximately 7 mm) at the moment of aortic dissection. Video available at: https://www.jtcvs.org/article/S0022-5223(22)00833-9/fulltext. A left-shift in the diameter for prophylactic aneurysmectomy: The right decision for all?The Journal of Thoracic and Cardiovascular SurgeryVol. 166Issue 2PreviewWith great interest we read the recent insightful report from the Yale Aortic Institute,1 resulting from efforts dedicated to studying the natural history, surgical management, and outcomes of thoracic aortic aneurysms (TAAs). Over the past decades, the authors have immensely contributed to disentangling the unknowns of this "silent-killer,"2 herewith supporting informed decision-making. Based on 5 arguments, in the current report the authors recommend a "left-shift" in the diameter for preemptive aneurysmectomy from 5.5 to 5.0 cm. Full-Text PDF

Background Data from the International Registry of Acute Aortic Dissection indicate that the guideline criterion of 5.5 cm for ascending aortic intervention misses many dissections occurring at smaller dimensions. Furthermore, studies of natural behavior have generally treated the aortic root and the ascending aorta as 1 unit despite embryological, anatomical, and functional differences. This study aims to disentangle the natural histories of the aforementioned aortic segments, allowing natural behavior to define specific intervention criteria for root and ascending segments of the aorta. Methods and Results Diameters of the aortic root and mid-ascending segment were measured separately. Long-term complications (dissection, rupture, and death) were analyzed retrospectively for 1162 patients with ascending thoracic aortic aneurysm. Cox regression analysis suggested that aortic root dilatation (P=0.017) is more significant in predicting adverse events than mid-ascending aortic dilatation (P=0.087). Short stature posed as a serious risk factor. The dedicated risk curves for the aortic root and the mid-ascending aorta revealed hinge points at 5.0 and 5.25 cm, respectively. Conclusions The natural histories of the aortic root and mid-ascending aorta are uniquely different. Dilation of the aortic root imparts a significant higher risk of adverse events. A diameter shift for intervention to 5.0 cm for the aortic root and to 5.25 cm for the mid-ascending aorta should be considered at expert centers.

We appreciate the thoughtful analysis of our study by Drs. Diao, Wu, and Manrai from the Informatics Program at Boston Children's Hospital. 1 Diao JA Wu GJ Manrai AK. Positive predictive value of the thumb-palm test for general population screening of ascending aortic aneurysm. Am J Cardiol. 2021; (In press) Google Scholar

Background. This study evaluates sex differences in the natural history of descending thoracic and thoracoabdominal aortic aneurysms (DTTAAs). Methods. In all, 907 patients with descending thoracic and thoracoabdominal aortic sizes greater than 3 cm were retrospectively reviewed. Growth rate estimates were performed utilizing an instrumental variables approach. Yearly complication rates as a function of aortic size were computed. Results. There were 615 men (67.8%) and 292 women (32.2%) treated between 1990 and 2018, with mean aortic diameters of 4.1 +/- 1.4 cm and 4.8 +/- 1.6 cm, respectively (P < .001). The mean growth rate of DTTAAs was 0.17 cm per year in men and 0.25 cm per year in women (P < .001), increasing with increasing aneurysm size. Dissection, rupture, or aortic death or the combination of the three occurred at double the rate for women compared with men (5.8% vs 2.3% per year for the combined endpoint). Diameter of DTTAA greater than 5 cm was associated with 26.3% (male) and 33.1% (female) average yearly rates of the composite endpoint of rupture, dissection, and death (P < .05). The probability of fatal complications (rupture and death) increased sharply at 5.75 cm in both sexes. Between 4.5 and 5.75 cm, there was another hinge-point of higher probability of fatal complications among women. Conclusions. Women diagnosed with DTTAA fare worse. Faster aneurysm growth and higher rates of dissection, rupture, and aortic death are apparent among women. Current guidelines recommend surgical intervention at 5.5 to 6 cm for DTTAAs without sex considerations. Our findings suggest that increased virulence of DTTAA in women may indicate surgery at a somewhat smaller diameter. (Ann Thorac Surg 2021;112:45-52) (c) 2021 by The Society of Thoracic Surgeons Superscript/Subscript Available

Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to "therapeutic" effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes ("filling out" of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with "normal" single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both "normal" and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33 %) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt. (C) 2020 Elsevier Inc. All rights reserved.

We have noticed, in caring for thousands of patients with ascending aortic aneurysm (AscAA), that the "thumb palm test" is often positive (with the thumb crossing beyond the edge of the palm). It is not known how accurate this test may be. We conducted the thumb-palm test in 305 patients undergoing cardiac surgery with intra-operative transesophageal echocardiography (TEE) for a variety of disorders: ascending aneurysm in 59 (19.4%) and non-AscAA disease in 246 (80.6%) (including CABG, valve repair, and descending aortic aneurysm). The TEE provided a precise ascending aortic diameter. The thumb palm test gave us a discrete, binary positive or negative result. We calculated the accuracy (sensitivity and specificity) of the thumb palm test in determining presence or absence of AscAA (defined as ascending aortic diameter > 3.8cm). Maximal ascending aortic diameters ranged from 2.0 to 6.6 cm (mean 3.48). 93 patients (30.6%) were classified as having an AscAA and 212 (69.4%) as not having an AscAA. 10 patients (3.3%) had a positive thumb-palm test and 295 patients (96.7%) did not. Sensitivity of the test (proportion of diseased patients correctly classified) was low (7.5%), but specificity (proportion of non-diseased patients correctly classified) was very high (98.5%). This study supports the utility of the thumb-palm test in evaluation for ascending thoracic aortic aneurysm. That is to say, a positive test implies a substantial likelihood of harboring an ascending aortic aneurysm. A negative test does not exclude an aneurysm. In other words, the majority of aneurysm patients do not manifest a positive thumb-palm sign, but patients who do have a positive sign have a very high likelihood of harboring an ascending aneurysm. We suggest that the thumb-palm test be part of the standard physical examination, especially in patients with suspicion of ascending aortic aneurysm (e.g. those with a positive family history).

While large pharmaceutical companies continue to dominate drug development and patent acquisition, their timing of drug patent acquisition and subsequent payoffs remain poorly understood. We analysed the effects of firm characteristics on the timing of patent purchases, with a unique data set constructed using publicly available data provided by the United States Patent and Trademark Office (USPTO). We focused on the role of firm size and composition in affecting the timing of patent purchases and the subsequent payoff; particularly, how firms' R&D intensity and overall scale affect purchasing decisions and commercial success of the drugs. The quantitative results show that, on average, firms with larger scale and stronger R&D departments are more likely to purchase drug patents later; furthermore, a strong R&D department contributes positively to drug sales and market shares through a better selection process of patents. The economics intuition is that firms with a larger scale and greater emphasis on R&D investment have advantages in producing in-house innovation, so they tend to be more selective when buying from outsources. This results in buying patents later and better subsequent commercial performance on the drugs that firms purchased.

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RESULTADOS Uma ExtAA de ≥13 cm esteve associada a uma taxa anual média de risco de EAAs quase cinco vezes maior comparada à taxa observada quando a ExtAA era <9 cm. Foram detectados dois “pontos de dobradiça” da ExtAA, com um aumento acentuado na probabilidade estimada de EAAs entre 11,5 e 12,0 cm, e entre 12,5 e 13,0 cm. A taxa anual média estimada de alongamento aórtico foi de 0,18 cm/ano, e o alongamento aórtico foi dependente da idade. O diâmetro aórtico aumentou 18% devido à dissecção, enquanto a ExtAA aumentou apenas 2,7%. Houve uma notável melhoria na discriminação do modelo de regressão logística (área sob a curva característica de operação do receptor: 0,810) devido à introdução do índice aorta/altura (IAA) (índice diâmetro/altura + índice extensão/altura). Os IAAs <9,33; 9,38 a 10,81; 10,86 a 12,50; e ≥12,57 cm/m estiveram associados em um risco anual médio de EAAs de ~4%, ~7%, ~12% e ~18%, respectivamente.

Background: Heart failure (HF) is a common, serious disease in the US and Europe. Patients with HF often require treatment for fluid overload, resulting in costly inpatient visits; however, limited evidence exists on the costs of alternative treatments. This study performed a cost-analysis of ultrafiltration (UF) vs diuretic therapy (DIUR-T) for patients with HF from the hospital perspective.Methods: The model used clinical data from the literature and hospital data from the Healthcare Cost and Utilization Project to follow a decision-analytic framework reflecting treatment decisions, probabilistic outcomes, and associated costs for treating patients with HF and hypervolemia with veno-venous UF or intravenous DIUR-T. A 90-day timeframe was considered to account for hospital readmissions beyond 30days. Sensitivity and scenario analyses were performed to gauge the robustness of the results.Results: Although initial hospitalization costs were higher, fluid removal by UF reduced hospital readmission days, leading to cost savings of $3,975 (14.4%) at the 90-day follow-up (UF costs, $23,633; DIUR-T costs, $27,608).Conclusions: UF is a viable alternative to DIUR-T when treating fluid overload in HF patients because it reduces hospital readmission rates and durations, which substantially lowers costs over a 90-day period compared to DIUR-T.

Aim: To quantify the healthcare expenditures for valvular heart disease (VHD) in the USA. Patients & methods: Direct annual incremental healthcare expenditures were estimated using multiple logistic and linear regression models. Results were stratified by age cohorts (18-64 years, ≥65 and ≥75 years) and disease status: symptomatic aortic valve disease (AVD), asymptomatic AVD, symptomatic mitral valve disease (MVD) and asymptomatic MVD. Results: A total of 1463 VHD patients were identified. The overall aggregated incremental direct expenditures were $56.62 billion ($26.48 billion for patients ≥75 years). Individuals ≥75 years with symptomatic AVD had the largest incremental effect on annual, per-patient healthcare expenditure of $30,949. The annualized incremental costs of VHD were greatest for individuals ≥75 years with AVD. Conclusion: Identification of VHD at an earlier stage may reduce the economic burden.

Objective: Recent studies indicate intraoperative hypotension, common in non-cardiac surgical patients, is associated with myocardial injury, acute kidney injury, and mortality. This study extends on these findings by quantifying the association between intraoperative hypotension and hospital expenditures in the US. Methods: Monte Carlo simulations (10,000 trial per simulation) based on current epidemiological and cost outcomes literature were developed for both acute kidney injury (AKI) and myocardial injury in non-cardiac surgery (MINS). For AKI, three models with different epidemiological assumptions (two models based on observational studies and one model based on a randomized control trial [RCT]) estimate the marginal probability of AKI conditional on intraoperative hypotension status. Similar models are also developed for MINS (except for the RCT case). Marginal probabilities of AKI and MINS sequelae (myocardial infarction, congestive heart failure, stroke, cardiac catheterization, and percutaneous coronary intervention) are multiplied by marginal cost estimates for each outcome to evaluate costs associated with intraoperative hypotension. Results: The unadjusted (adjusted) model found hypotension control lowers the absolute probability of AKI by 2.2% (0.7%). Multiplying these probabilities by the marginal cost of AKI, the unadjusted (adjusted) AKI model estimated a cost reduction of $272 [95% CI = $223-$321] ($86 [95% CI = $47-$127]) per patient. The AKI model based on relative risks from the RCT had a mean cost reduction estimate of $281 (95% CI = -$346-$750). The unadjusted (adjusted) MINS model yielded a cost reduction of $186 [95% CI = $73-$393] ($33 [95% CI = $10-$77]) per patient. Conclusions: The model results suggest improved intraoperative hypotension control in a hospital with an annual volume of 10,000 non-cardiac surgical patients is associated with mean cost reductions ranging from $1.2-$4.6 million per year. Since the magnitude of the RCT mean estimate is similar to the unadjusted observational model, the institutional costs are likely at the upper end of this range.