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

This issue of the () 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: .

Ascending Aneurysms in Heart Transplant Patients: A Rare Opportunity to Assess Heredity Versus Biological Environment.

Three patients developed severe ascending aortic aneurysm requiring surgical resection after heart transplantation. In all 3 cases, the donor aorta of the transplant remained normal in caliber, despite the development of a large aneurysm in the native upper ascending aorta. The aneurysmal disease did not cross the suture line.

Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?

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.

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

 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.  A retrospective review of all TAAD patients who underwent an open repair since January 2000 was performed.

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.

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.

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.

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.

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.

Early Spontaneous Resolution of an Iatrogenic Acute Type A Aortic Dissection.

Acute aortic dissection is a rare but devastating complication during cardiac catheterization. We present the case of an elderly female who incurred a Stanford Type A/DeBakey Type I acute aortic dissection extending into the arch vessels and descending aorta likely occurring during right coronary artery engagement for angioplasty. The patient was treated successfully by immediately sealing the entrance of the dissection via the placement of a stent and anti-impulse therapy.

Positive family history of aortic dissection dramatically increases dissection risk in family members.

Objectives: Although family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives.

Methods: Patients with AoD at our institution were analyzed for information of FHAD.

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.

719Arg Genetic Variant and Risk for Thoracic Aortic Dissection.

Background: Carriers of the 719Arg variant in , 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 719Arg carrier status and thoracic aortic dissection, and between 719Arg carrier status and nondissection thoracic aortic aneurysm, using logistic regression models adjusted for age, sex, hypertension, smoking, and country.

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.

Advanced Glycation End Products and its Soluble Receptors in the Pathogenesis of Thoracic Aortic Aneurysm.

Background: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines.

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.

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.

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.

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.

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.

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.

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.

Management of Coronary Artery Disease in Patients With Descending Thoracic Aortic Aneurysms.

Background: The combination of descending aortic aneurysm (DAA) with concomitant coronary artery disease (CAD) is associated with increased morbidity and mortality. We review the surgical management for patients with this combined disease.

Methods: From January 2000 to January 2014, we performed 268 elective surgeries on the descending or thoracoabdominal aorta.

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.

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.