"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.

Open Replacement of the Thoracoabdominal Aorta: Short- and Long-term Outcomes at a Single Institution.

Background Despite much progress in the surgical and endovascular treatment of thoracoabdominal aortic diseases (TAADs), there is no consensus regarding the optimal approach to minimize operative mortality and end-organ dysfunction. We report our experience in the past 16 years treating TAAD by open surgery. Methods A retrospective review of all TAAD patients who underwent an open repair since January 2000 was performed. The primary endpoints included early morbidity and mortality, and the secondary endpoints were overall death and rate of aortic reintervention. Results There were 112 patients treated by open surgery for TAAD. Mean age was 66 ± 10 years and 61 (54%) were male. Seventy-seven (69%) patients had aneurysmal degeneration without aortic dissection and the remaining 35 (31%) had a concomitant aortic dissection. There were 12 deaths (10.7%) and they were equally distributed between the aneurysm and dissection groups ( p = 0.8). The mortality for elective surgery was 3.2% (2/61). The rate of permanent paraplegia and stroke were each 2.6% (3/112). The rate of cerebrovascular accident was significantly higher in the dissection group (8.5% vs. 1.2%, p = 0.05). The survival at 1, 5, and 10 years was 80.6, 56.1, and 32.7%, respectively. Conclusion Our data confirm that open replacement of the thoracoabdominal aorta can be performed in expert centers quite safely. Different aortic pathologies (degenerative aneurysm vs. dissection) do not influence the short- and long-term outcomes. Open surgery should still be considered the standard in the management of TAAD.

Height alone, rather than body surface area, suffices for risk estimation in ascending aortic aneurysm.

BACKGROUND: In international guidelines, risk estimation for thoracic ascending aortic aneurysm (TAAA) is based on aortic diameter. We previously introduced the aortic size index (ASI), defined as aortic size/body surface area (BSA), as a predictor of aortic dissection, rupture, and death. However, weight might not contribute substantially to aortic size and growth. We seek to evaluate the height-based aortic height index (AHI) versus ASI for risk estimation and revisit our natural history calculations. METHODS: Aortic diameters and long-term complications of 780 patients with TAAA were analyzed. Growth rate estimates, yearly complication rates, and survival were assessed. Risk stratification was performed using regression models. The predictive value of AHI and ASI was compared. RESULTS: Patients were stratified into 4 categories of yearly risk of complications based on their ASI and AHI. ASIs (cm/m2) of ≤2.05, 2.08 to 2.95, 3.00 to 3.95 and ≥4, and AHIs (cm/m) of ≤2.43, 2.44 to 3.17, 3.21 to 4.06, and ≥4.1 were associated with a 4%, 7%, 12%, and 18% average yearly risk of complications, respectively. Five-year complication-free survival was progressively worse with increasing ASI and AHI. Both ASI and AHI were shown to be significant predictors of complications (P < .05). AHI categories 3.05 to 3.69, 3.70 to 4.34, and ≥4.35 cm/m were associated with a significantly increased risk of complications (P < .05). The overall fit of the model using AHI was modestly superior according to the concordance statistic. CONCLUSIONS: Compared with indices including weight, the simpler height-based ratio (excluding weight and BSA calculations) yields satisfactory results for evaluating the risk of natural complications in patients with TAAA.

Direct axillary cannulation with open Seldinger-guided technique: is it safe?

OBJECTIVES: Axillary artery cannulation is commonly used in thoracic aortic surgery, often utilizing a sidearm graft. Although our institutional preference is femoral cannulation, we use axillary cannulation in select cases with a 'dirty' aorta on computed tomography scan or intraoperative transoesophageal echocardiography. Since 2011, we have routinely used an open Seldinger-guided approach for axillary cannulation. Here, we report our experience with open Seldinger-guided technique, evaluating its safety and efficacy. METHODS: A retrospective analysis of our institutional database from 2011 to 2016 was performed to find cases of peripheral arterial cannulation for thoracic aortic surgery. We identified 404 consecutive patients who underwent peripheral arterial cannulation. Of these, 352 were femoral and 52 were axillary cannulations. All axillary cannulations were performed for ascending and/or arch surgery. The technique involves a surgical exposure of the artery which is then cannulated by guidewire inside a purse string without arterial incision. RESULTS: Indications for surgery included aneurysm in 63.5% (33/52), dissection in 30.7% (16/52) and pseudoaneurysm in the remaining 5.8% (3/52). Hospital survival was 98.1% (51/52). There were no instances of axillary arterial injury or intraoperative malperfusion phenomena. No postoperative limb ischaemia or stroke was evident. No wound infections or late pseudoaneurysms were observed. CONCLUSIONS: The open Seldinger-guided technique for axillary artery cannulation is safe and effective. We strongly recommend this technique, given its speed and simplicity. The vessel is not snared, thereby preserving distal arterial flow and minimizing the risk of acute limb ischaemia. Furthermore, the limited manipulation of the artery lowers the risk of local complications.

Favorable late survival after aortic surgery under straight deep hypothermic circulatory arrest.

BACKGROUND: Surgical and cerebral protection strategies in aortic arch surgery remain under debate. Perioperative results using deep hypothermic circulatory arrest (DHCA) have been associated with favorable short-term mortality and stroke rates. The present study focuses on late survival in patients undergoing aortic surgery using DHCA. METHODS: A total of 613 patients (mean age, 63.7 years) underwent aortic surgery between January 2003 and December 2015 using DHCA, with 77.3% undergoing hemiarch replacement and 20.4% undergoing arch replacement, with a mean DHCA duration of 29.7 ± 8.5 minutes (range, 10-62 minutes). We examined follow-up extending up to a mean of 3.8 ± 3.4 years (range, 0-14.1 years). RESULTS: Operative mortality was 2.9%, and the stroke rate was 2%. Survival was 92.2% at 1 year and 81.5% at 5 years, significantly lower than the values in an age- and sex-matched reference population. In elective, nondissection first-time surgeries (n = 424), survival was similar to that of the reference group. Acute type A aortic dissection (hazard ratio [HR], 4.84; P = .000), redo (HR, 4.12; P = .000), and descending aortic pathology (HR, 5.54: P = .000) were independently associated with reduced 1-year survival. Beyond 1 year, age (HR, 1.07; P = .000), major complications (HR, 3.11; P = .000), and atrial fibrillation (HR, 2.47; P = .006) were independently associated with poor survival. DHCA time was not significantly associated with survival in multivariable analysis. CONCLUSIONS: Aortic surgery with DHCA can be performed with favorable late survival, with the duration of DHCA period having only a limited impact. However, these results cannot be generalized for very long durations of DHCA (>50 minutes), when perfusion methods may be preferable. In elective, nondissection first-time surgeries, a late survival comparable to that in a reference population can be achieved. Early survival is adversely affected by aortic dissection, redo status, and disease extent.

Does BioGlue contribute to anastomotic pseudoaneurysm after thoracic aortic surgery?

BACKGROUND: Although bovine serum albumin-glutaraldehyde glue (BioGlue®) has been successfully used as a hemostatic adjunct in aortic surgical procedures, there are reports that it may lead to anastomotic pseudoaneurysm formation. We seek to examine if the use of BioGlue is associated with a high incidence of anastomotic pseudoaneurysm formation following surgical repair of thoracic aortic disease. METHODS: We reviewed the medical records and follow-up computed tomography (CT) scans of patients from 2001 to 2015 in whom BioGlue was used during surgical repair of thoracic aortic disease to detect postoperative anastomotic pseudoaneurysm formation. RESULTS: A total of 233 patients with BioGlue use were identified. Mean age was 63.5±14.0 years (median 66; range 14-88; 25-75%, IQR 54-74 years) and 149 were male (63.9%). Surgical indication was thoracic aortic aneurysm in 169 (72.5%) patients, aortic dissection in 49 (21.0%), intramural hematoma in 9 (3.9%), penetrating aortic ulcer in 3 (1.3%) and other in 3 (1.3%). Emergency/urgent surgery was performed in 68 cases (29.2%). Operative mortality was 7.3% (17/233). Re-exploration for bleeding and neurologic deficits occurred in 24 (10.3%) and 21 (9.0%) patients respectively. All operative survivors were followed (100%, 216/216) and CT follow-up was available in 81.9% (177/216) for a mean duration of 2.4 years (median 0.6; 25-75% IQR 0.2-3.6 years). Anastomotic pseudoaneurysm was detected in 1 patient (0.6%) at 3 years postoperatively. This was an elderly female with extremely frail tissues who underwent a reoperative ascending and arch replacement for dissection. CONCLUSIONS: The use of BioGlue in thoracic aortic surgery was not associated with excess incidence of anastomotic pseudoaneurysm formation following surgical repair of thoracic aortic disease. Its use need not be discouraged on this basis.

In DeBakey Type I Aortic Dissection, Bovine Aortic Arch Is Associated With Arch Tears and Stroke.

BACKGROUND: The study sought to evaluate if a bovine aortic arch (BAA) influences the location of the entry site in acute aortic dissection type A (AADA) and to identify the impact of BAA on postoperative outcome, especially stroke. METHODS: A total of 315 patients underwent surgery due to AADA DeBakey type I (72.1% men, mean age 59.5 ± 13.4 years) between 2002 and 2015. Imaging studies and operative reports were screened for presence of BAA and location of the entry site. Patients were divided into 2 groups based on presence (BAA+) and absence (BAA-) of BAA (BAA+ n = 49, BAA- n = 264). Dissection patterns, surgical treatment, risk factors for postoperative complications, and long-term outcome were analyzed. RESULTS: Prevalence of BAA in patients with AADA was 15.6%. Location of the entry site was more commonly in the aortic arch in patients with BAA (BAA+ 46.8% versus BAA- 14.3%; p < 0.001). Multivariable analysis identified BAA (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.89 to 12.04; p < 0.001) and preoperative competent aortic valve (OR, 2.26; 95% CI, 1.19 to 4.31; p = 0.013) as independent predictors for an arch tear. Thirty-nine patients (12.4%) suffered from stroke. Patients with BAA had higher stroke rates (BAA+ 24.5% versus BAA- 10.2%; p = 0.009). BAA emerged as one risk factor for stroke in the setting of AADA (OR, 2.69; 95% CI, 1.2 to 6.0; p = 0.016). Long-term survival was comparable for patients with BAA and patients without congenital arch anomalies. CONCLUSIONS: BAA is an independent predictor for the distinctive location of the entry site in the aortic arch and risk factor for stroke.

V-shape noncoronary sinus remodeling in ascending aortic aneurysm and aortic root ectasia.

OBJECTIVE: The study objective was to describe our initial experience performing a V-shaped single sinus remodeling procedure in patients with ascending aortic aneurysm and moderate aortic root ectasia. METHODS: Twelve consecutive patients underwent supracoronary ascending aortic replacement with V-shaped noncoronary sinus remodeling (median age, 63 years [range, 56-77]; 10 patients [83%] were male). All patients had an ascending aortic aneurysm (median diameter 48 mm [range, 42-53]) and aortic root ectasia (median root diameter, 43 mm [range, 38-49.7 mm]). A deep V-shaped (triangular) portion of the noncoronary sinus was excised, and the wall was directly reapproximated in 2 layers, 1 everting mattress suture layer followed by a running over-and-over layer. RESULTS: No technical complication due to root remodeling was observed. All patients survived the initial hospitalization. Only 1 patient required reexploration for bleeding, unrelated to the V-shaped repair. On postoperative computed tomography, every patient showed reduction in maximal aortic root diameter and cross-sectional area. Mean aortic root diameter was reduced from 4.30 cm (range, 3.82-4.97) to 3.81 cm (range, 3.58-3.96) (P < .0006). Mean aortic root cross-sectional area was reduced from 1452 mm2 (range, 1327-1615) to 1180 mm2 (range, 961-1328) (P < .0002). Mean wall tension decreased postoperatively by 12%. CONCLUSIONS: The V-shaped resection of the noncoronary sinus is a viable option for patients with moderate aortic root enlargement. This technique reduces aortic root diameter, cross-sectional area, and wall tension. We offer this technique as another option in the surgeon's armamentarium.

Do Familial Aortic Dissections Tend to Occur at the Same Age?

BACKGROUND: Prediction of the age at aortic dissection for family members of aortic dissection patients would enhance early detection and clinical management. We sought to determine whether these dissections tend to cluster by age in family members of the dissection patients. METHODS: Ages at dissection were examined, including 51 sporadic dissectors (one dissection in family) and 39 familial dissectors (two or more dissections in family) from 16 families. Differences between sporadic and familial dissectors and relationships between ages at dissection in family members were analyzed by linear regression and clustering analysis. RESULTS: Age at dissection was significantly younger in familial versus sporadic dissectors (54.1 ± 15.2 years versus 63.1±12.4 years, p = 0.002). Regression analysis of pairs of family member ages at dissection found a moderately close linear fit (R2 = 0.35). Cluster analysis indicated that age at onset of family dissectors increases as age of proband dissector increases. More than 50% of familial dissections occurred within 10 years of the median onset age for any given age decade. For familial dissectors with onset age of 30 to 49 years, 71% of other family member dissections also occurred at age 30 to 49 years, and no dissections occurred above the age of 63 years. For familial dissectors with onset age of 60 to 79 years, 80% of other family member dissections occurred beyond the age of 50 years. CONCLUSIONS: Familial dissections occur earlier than sporadic dissections. Dissections cluster by age in families, and age at onset can predict the age of other dissectors. This finding argues for consideration of prophylactic resection of an aneurysm in family members approaching the age at onset of prior thoracic aortic dissection.

Twenty-five year outcomes following composite graft aortic root replacement.

BACKGROUND: Operative choices for aortic root disease include traditional root replacement with a composite valved graft as well as various valve-sparing and root repair procedures. OBJECTIVES: To report our experience with traditional composite graft aortic root replacement by a single surgeon over a 25-year period in 449 patients, focusing on long-term survival and freedom from late reoperation and adverse events. METHODS: The coronary button technique was used in all patients. Mean age was 56.1 ± 14.0 years (range 14-87) with 83% males (373/449). Valve prosthesis was mechanical in 343 (76%) and bioprosthetic in 106 (24%). A modified Cabrol procedure (Dacron coronary graft) was employed in 10% (45/449) and concomitant coronary artery bypass graft in 10.9% (49/449). There were 15.8% (71/449) urgent/emergent and 8.2% (37/449) redo procedures. Survival follow-up was 100%. Mean follow-up was 7.0 ± 5.1 years (range 0.1-24.8). RESULTS: Operative mortality occurred in 14 patients (3.1%) and was 2.2% (9/418) in non-dissection and 1.9% (7/361) in elective first-time operations. Stroke and re-exploration for bleeding occurred in nine (2.0%) and 20 (4.5%) patients, respectively. Major late events included bleeding in 2.5% (11/435) and thromboembolism in 1.1% (5/435). At 5, 10, and 20 years, freedom from major events and reoperations on the root were 97.8, 95.4, and 94.39%, and 99.0, 99.0, and 97.9%, respectively. Survival in patients aged <60 years was 92.0, 90.1, and 79.8% at five, 10, and 20 years versus 88.4, 67.9, and 42.6% in patients aged ≥60 years (p = 0.001). Compared with age- and gender-matched controls, survival was not significantly different (p = 0.20). CONCLUSIONS: Composite graft aortic root replacement is associated with low operative risk, excellent long-term survival, and low incidence of reoperation and late events.

Aortic valve disease with ascending aortic aneurysm: Impact of concomitant root-sparing (supracoronary) aortic replacement in nonsyndromic patients.

OBJECTIVE: The purpose of the study was to assess the anticipated incremental risk of a concomitant aortic resection performed with an aortic valve replacement. METHODS: Patients who underwent aortic valve replacement with root-sparing ascending replacement were compared with those who underwent isolated aortic valve replacement using propensity score matching (81 pairs; mean age, 63 ± 11 years [root-sparing ascending replacement] vs 64 ± 14 years). To evaluate the impact of the technique at distal site, 71 pairs of those undergoing root-sparing ascending replacement also were matched by propensity score according to distal anastomosis performed clamped and open under deep hypothermic circulatory arrest. RESULTS: Operative mortality was equal between the root-sparing ascending replacement and isolated aortic valve replacement groups. No significant difference was found regarding postoperative morbidities, such as bleeding, renal failure, stroke, and length of stay, except prolonged ventilation was found after root-sparing procedures (P = .028). Survival estimation showed no difference between the groups. Comparing the patients undergoing root-sparing ascending replacement with clamped and opened distal anastomosis revealed a prolonged ventilation requirement (7% vs 3%; P = not significant) in the open group. Operative mortality was 0% in both groups, and midterm survival was comparable. CONCLUSIONS: The concomitant replacement of the aorta in root-sparing fashion is associated with an excellent operative outcome and adds no additional risk to aortic valve replacement in elective and non-high-risk patients. If the distal anastomosis is performed in an open fashion, while the operative mortality is still very low, morbidities are slightly higher, but midterm survival remains comparable.

Neuromonitoring Using Motor and Somatosensory Evoked Potentials in Aortic Surgery.

BACKGROUND: Motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) are established methods of neuromonitoring aimed at preventing paraplegia after descending or thoracoabdominal aortic repair. However, their predictive impact remains controversial. The aim of this study was to evaluate our single-center experience using this monitoring technique. METHODS: Between 2009 and 2014, 78 patients (mean age 66 ± 12, 53% male) underwent either descending or thoracoabdominal aortic repairs. Of these, 60% had an aortic aneurysm, 30% dissection, and 10% other etiologies. Intraoperatively, MEPs and SSEPs were monitored and, if necessary, clinical parameters (blood pressure, hematocrit, oxygenation) were adjusted in response to neuromonitoring signals. This analysis is focused on the neurological outcome (paraplegia, stroke) after the use of intraoperative neuromonitoring. RESULTS: Thirty-day mortality was 10 (12.8%). All patients with continuously stable signals or signals that returned after signal loss developed no spinal cord injury, whereas two out of six of the evaluable patients with signal loss (without return) during the procedure suffered from postoperative paraplegia (one transient and one permanent). Sensitivity and specificity of use of MEP and SSEP were 100% and 94.20% regarding paraplegia, respectively. CONCLUSIONS: (1) Preservation of signals or return of signals is an excellent prognostic indicator for spinal cord function. (2) Intraoperative modifications in direct response to the signal change may have averted permanent paralysis in the patients with signal loss without neurologic injury. We have found MEP and SSEP neuromonitoring to be instrumental in the prevention of paraplegia. doi: 10.1111/jocs.12739 (J Card Surg 2016;31:383-389).

Sparing the aortic root in acute aortic dissection type A: risk reduction and restored integrity of the untouched root.

OBJECTIVES: The purpose of the study was to evaluate the operative outcome and the risk of retained proximal aortic tissue following the root-sparing (RS) technique in acute aortic dissection type A (AADA). METHODS: Between 2002 and 2014, 338 patients underwent repair of AADA; 74% of those were performed with the RS technique and 26% with root replacement (RR). The mean age was 62.4 ± 13.4 years (69% male) in the RS group and 56.1 ± 13.1 years (76% male) in the RR group (P < 0.001). Aortic insufficiency 2+ or higher was present in 35% (RS) and 72% (RR, P < 0.001), and bicuspid morphology in 1% (RS) and 16% (RR, P < 0.001). RESULTS: Cardiopulmonary bypass time and cross-clamp time were significantly lower in the RS group (199 ± 71 vs 274 ± 110 min; 108 ± 46 vs 169 ± 55 min; P < 0.001 each), while no difference was seen with regard to distal operative extent, the use of circulatory arrest and adjunct protection strategies. The postoperative incidence of bleeding (18 vs 34%; P = 0.003), low cardiac output (14 vs 29%; P = 0.002) and sepsis/systemic inflammatory response syndrome (5 vs 12%; P = 0.037) were higher after RR, whereas mortality and survival did not differ between the groups. The aortic root grows at 0.40 ± 0.13 mm/year after AADA and thus, the need for potential reoperation was estimated at greater than 40 years. Freedom from root events after 5 and 10 years of follow-up was 97 and 92% in the RS group, and 100% each in RR group, respectively. CONCLUSIONS: Both RS and RR procedures can be performed with an acceptable postoperative outcome and late survival in AADA. The RS approach can safely be performed with excellent results in acute survival and stabilizes the native root for a long period of time.

Simple Renal Cysts as Markers of Thoracic Aortic Disease.

BACKGROUND: Thoracic aortic aneurysm is usually a clinically silent disease; timely detection is largely dependent upon identification of clinical markers of thoracic aortic disease (TAD); (bicuspid aortic valve, intracranial aortic aneurysm, bovine aortic arch, or positive family history). Recently, an association of simple renal cysts (SRC) with abdominal aortic aneurysm and aortic dissection was established. The aim of our study was to evaluate the prevalence of SRC in patients with TAD in order to assess whether the presence of SRC can be used as a predictor of TAD. METHODS AND RESULTS: We evaluated the prevalence of SRC in 842 patients with TAD (64.0% males) treated at our institution from 2004 to 2013 and compared to a control group of patients (n=543; 56.2% males). Patients were divided into 4 groups: ascending aortic aneurysm (456; 54.2%); descending aortic aneurysm (86; 10.2%); type A aortic dissection (118; 14.0%); and type B aortic dissection (182; 21.6%). SRC were identified by abdominal computed tomography or magnetic resonance imaging of these patients. Prevalence of SRC is 37.5%, 57.0%, 44.1%, and 47.3% for patients with ascending aneurysm, descending aneurysm, type A dissection, and type B dissection, respectively. Prevalence of SRC in the control group was 15.3%. Prevalence of SRC was not significantly different between male and female aortic disease patients, despite reported general male predominance (2:1), which was also observed in our control group (1.7:1). CONCLUSIONS: This study establishes an increased prevalence of SRC in patients with TAD. SRC can potentially be used as a marker for timely detection of patients at risk of TAD.

Long-term behavior of aortic intramural hematomas and penetrating ulcers.

OBJECTIVE: For intramural hematoma and penetrating atherosclerotic ulcer, long-term behavior and treatment are controversial. This study evaluates the long-term behavior of intramural hematoma and penetrating atherosclerotic ulcer, including radiologic follow-up and survival analysis. METHODS: Between 1995 and 2014, 108 patients (mean age, 70.8 ± 10 years; 56% female) presented with intramural hematoma or penetrating atherosclerotic ulcer to Yale-New Haven Hospital (New Haven, Conn). We reviewed the medical records, radiology, and online mortality databases. RESULTS: Ten of 55 patients (18%) with intramural hematoma and 17 of 53 patients (32%) with penetrating atherosclerotic ulcer had rupture state symptoms on admission, both greater than type A (8%) or type B dissection (4%) (P < .001). No branch vascular occlusion occurred. For patients with intramural hematoma with follow-up imaging, 8 of 14 (57%) worsened (mean follow-up, 9.4 months) and 6 (43%) underwent late surgery. For patients with penetrating atherosclerotic ulcer with follow-up imaging, 6 of 20 (30%) worsened and underwent late surgery, and 11 (55%) showed no change (mean follow-up, 34.3 months). Overall survivals were 77%, 70%, 58%, and 33% at 1, 3, 5, and 10 years, respectively. No operative deaths occurred for patients with nonrupture state. Patients with penetrating atherosclerotic ulcer with initial surgical treatment had better long-term survival than patients treated medically (P = .037). In the intramural hematoma group, no such difference was observed (P = .10). CONCLUSIONS: At presentation, the incidence of early rupture of intramural hematoma and penetrating atherosclerotic ulcer was higher than for typical dissection. For branch vessels, intramural hematoma never occludes branch arteries. On imaging follow-up, patients with intramural hematoma and penetrating atherosclerotic ulcer rarely improved, with late surgery commonly needed. Better survival was observed for the initial surgical management of patients with penetrating atherosclerotic ulcer compared with initial medical management.

KIF6 719Arg Genetic Variant and Risk for Thoracic Aortic Dissection.

BACKGROUND: Carriers of the 719Arg variant in KIF6, compared with noncarriers, have been reported to be at greater risk for coronary heart disease (CHD) in six prospective studies. Because CHD, thoracic aortic dissection, and nondissection thoracic aortic aneurysm share some risk factors and aspects of pathophysiology, we investigated whether carriers of the 719Arg variant also have greater odds of thoracic aortic dissection or nondissected thoracic aortic aneurysm than noncarriers. METHODS: We genotyped 140 thoracic aortic dissection cases, 497 nondissection thoracic aortic aneurysm cases, and 275 disease-free controls collected in the United States, Hungary, and Greece and investigated the association between KIF6 719Arg carrier status and thoracic aortic dissection, and between KIF6 719Arg carrier status and nondissection thoracic aortic aneurysm, using logistic regression models adjusted for age, sex, hypertension, smoking, and country. RESULTS: The odds of aortic dissection were two-fold greater in KIF6 719Arg carriers compared with noncarriers (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.18-3.9). To account for the potential of concomitant CHD to confound the association between the KIF6 719Arg and thoracic aortic dissection, we repeated the analysis after removing subjects with concomitant CHD; the estimates for association of KIF6 719Arg carrier status remained essentially the same (OR 2.04, 95% CI 1.11-3.77). In contrast, KIF6 719Arg carrier status was not associated with risk for nondissection thoracic aortic aneurysm. CONCLUSIONS: We observed an association of the KIF6 719Arg genetic variant with thoracic aortic dissection in this multicenter case-control study. This association may enhance our management of patients with thoracic aortic disease.

Current Experience With Acute Type B Aortic Dissection: Validity of the Complication-Specific Approach in the Present Era.

BACKGROUND: Our group proposed in 1992 a "complication-specific approach" for the management of acute aortic dissection type B (TBAD), with uncomplicated cases being treated with medical therapy. In this study, we evaluate the efficacy of this management in in-hospital and postdischarge survival. METHODS: Between 1999 and 2014, 123 consecutive acute TBAD patients were treated at our institution. We compared complicated (rupture/impending rupture, malperfusion, expansion) vs uncomplicated TBAD, as well as TBAD with a dissection flap vs intramural hematoma/penetrating aortic ulcer. RESULTS: A total of 103 patients (84%) were strictly managed according to the complication-specific approach, with 93% in-hospital survival. Twenty deviated from complication-specific approach management (triaged to operation by complication-specific approach, but inoperable for a variety of reasons). Independent risk factors for a complicated course in the dissection flap subgroup (n = 89) were history of coronary artery disease (odds ratio. 3.139; p = 0.04) and maximum aortic diameter exceeding 5 cm (odds ratio, 4.586; p = 0.005). Uncomplicated patients were treated medically with antiimpulse therapy. Among the 103 patients treated with the complication-specific approach, long-term survival was 83%, 78%, 71% and 47% at 1, 3, 5, and 10 years, respectively. Between the uncomplicated and complicated groups, 8-year survival was 55% and 49%, respectively (log-rank p = 0.03). Uncomplicated patients showed comparable 6-year survival (log-rank p = 0.06) to matched normal population controls. CONCLUSIONS: Patients managed with the complication-specific approach showed an overall satisfactory long-term survival over 10 years. No in-hospital deaths occurred in patients with uncomplicated, medically treated acute TBAD, with comparable long-term survival to a matched normal population. These good long-term results provide counterbalancing perspective when considering routine thoracic endovascular aortic repair for all TBAD patients.

Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting.

BACKGROUND: Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES). Here we present our initial results. METHODS: The WES was performed in 102 patients (mean age 56.8 years; range 13 to 83; 70 males [68.6%]) with TAAD. The following 21-gene panel was tested by WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2. RESULTS: Seventy-four patients (72.5%) had no medically important genetic alterations. Four patients (3.9%) had a deleterious mutation identified in the FBN1, COL5A1, MYLK, and FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants of unknown significance were identified in 1 or more of the following genes: FBN1 (n = 5); MYH11 (n = 4); ACTA2 (n = 2); COL1A1 (n = 2); TGFBR1 (n = 2); COL3A1 (n = 1); COL5A1 (n = 1); COL5A2 (n = 1); FLNA (n = 1); NOTCH1 (n = 1); PRKG1 (n = 1); and TGFBR3 (n = 1). Identified mutations had implications for clinical management. CONCLUSIONS: Routine genetic screening of patients with TAAD provides information that enables genetically personalized care and permits identification of novel mutations responsible for aortic pathology. Analysis of large data sets of variants of unknown significance that include associated clinical features will help define the mutational spectrum of known genes underlying this phenotype and potential identify new candidate loci.

Chronic Traumatic Thoracic Aortic Aneurysm: 40-Year Follow-Up.

Traumatic aortic injury is a rare but potentially lethal condition. Those few patients who survive the acute phase of injury usually progress to form a chronic aneurysm. Few guidelines exist on the management of chronic traumatic aortic aneurysms. Here, we describe the conservative management of a patient with a traumatic thoracic aortic aneurysm who has remained asymptomatic for 40 years.

Atypical aortic arch branching variants: A novel marker for thoracic aortic disease.

OBJECTIVE: To examine the potential of aortic arch variants, specifically bovine aortic arch, isolated left vertebral artery, and aberrant right subclavian artery, as markers for thoracic aortic disease (TAD). METHODS: We screened imaging data of 556 patients undergoing surgery due to TAD for presence of aortic arch variations. Demographic data were collected during chart review and compared with a historical control group of 4617 patients. RESULTS: Out of 556 patients with TAD, 33.5% (186 patients) demonstrated anomalies of the aortic arch, compared with 18.2% in the control group (P < .001). Three hundred seventy (66.5%) had no anomaly of the aortic arch. Bovine aortic arch emerged as the most common anomalous branch pattern with a prevalence of 24.6% (n = 137). Thirty-five patients (6.3%) had an isolated left vertebral artery, and 10 patients (1.8%) had an aberrant right subclavian artery. When compared with the control group, all 3 arch variations showed significant higher prevalence in patients with TAD (P < .001). Patients with aortic aneurysms and anomalous branch patterns had hypertension less frequently (73.5% vs 81.8%; P = .048), but had a higher rate of bicuspid aortic valve (40.8% vs 30.6%; P = .042) when compared with patients with aneurysms but normal aortic arch anatomy. Patients with aortic branch variations were significantly younger (58.6 ± 13.7 years vs 62.4 ± 12.9 years; P = .002) and needed intervention for the aortic arch more frequently than patients with normal arch anatomy (46% vs 34.6%; P = .023). CONCLUSIONS: Aortic arch variations are significantly more common in patients with TAD than in the general population. Atypical branching variants may warrant consideration as potential anatomic markers for future development of TAD.