2022 AHA科学声明：慢性主动脉夹层的影像学检查和监测

PATHOPHYSIOLOGY

Several alterations occur over time in the dissected aorta. Above all, the dissected aorta grows more rapidly than the nondissected aorta (3.1 mm/y versus 0.5 mm/y).$^{46}$ Recent studies from multiple centers have confirmed these estimates, revealing growth rates of 2.3 to 4.1 mm/y.$^{47-50}$ A detailed study from the Aortic Institute at Yale University showed that growth during the first few days after aortic dissection is rapid but decreases substantially by 30 days to a slow but inexorable growth (Figure 3).$^{51}$ In the same study, Peterss and colleagues$^{51}$ revealed that the initial remodeling phase of the outer false lumen aortic wall is characterized pathologically by a high grade of cellular destruction in the aortic media, followed by substantial fibrosis in the chronic phase. In the absence of intact medial smooth muscle cells, adventitial fibroblasts remain as the primary cell population responsible for restoring and maintaining the structural integrity of the outer wall of the aortic false lumen.$^{11}$

Similar pathological changes alter the dissection flap over time, which becomes thicker, fibrotic, and less

mobile. The increasing stiffness of the dissection membrane increases pressure gradients between the true lumen and false lumen.$^{10}$

Late Complications

In addition to the common but gradual development of false lumen aneurysms large enough to warrant executive repair, patients with chronic aortic dissection remain at risk for less common but acute and potentially lethal events requiring emergency intervention.$^{30}$

Emergency Late Complications

Approximately 6% of patients with chronic dissection require an emergency intervention to treat new limb or mesenteric ischemia.$^{41}$ New dissections or redissections occurred in ≈5% of patients in 2 single-center studies.$^{52,53}$ New type A dissections in patients with chronic type B dissections occurred in 3.6% of medically managed patients, 4.3% of patients undergoing open aortic surgery, and 6.9% of patients with TEVAR.$^{52}$ Acute redissection of a chronically dissected distal aorta, resulting in a new, third flow channel, is strongly associated with Marfan syndrome (21.5% versus 3.1%).$^{53}$ Ensuing further thinning of the already dissected wall requires prompt intervention (Supplemental Figure 1). The most feared complication, late aortic rupture, is reported in 3% to 18%.$^{54-56}$ However, the actual rate is difficult to establish because, in most patients undergoing surveillance who die suddenly, a cause is not identified.

Aneurysm Formation

Aneurysms develop in 34% to 38% of patients with chronic type B aortic dissection$^{26,55,56}$ and in up to 49% of patients with residual chronic aortic dissection in the distal aorta after type A aortic repair.$^{57}$ Aneurysm formation is the primary reason for reoperations in patients with chronic aortic dissection.$^{55}$ Reoperation rates in residual chronic type A aortic dissection range between 9% and 27.5%, with some patients requiring >1 reintervention.$^{27,54,57}$ Intervention-free survival in type B aortic dissection is reported to be between 41% and 66%, depending on complication status at the initial event.$^{24,55,56}$

Hemodynamics and Mechanobiology

The complex interplay among morphological, hemodynamic, and biomechanical factors contributing to false lumen degeneration and aneurysm formation is incompletely understood. This is a critical gap in our knowledge that impedes our efforts to solve important problems. First, we currently lack reliable prediction models to guide treatment in patients with uncomplicated type B aortic dissection.$^{58}$ We possess a wealth of imaging data attesting to the vast individual variation of aortic dissection manifestations. However, without understanding how an individual's constellation of dissection features translates

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 Figure 3. Morphological changes in aortic dissection.

Orthogonal cross sections through the descending thoracic aorta at baseline (day 1) and 3 months, 6 months, 3 years, 8 years, and 9 years after the acute event. In the acute phase, the dissection flap (arrowheads) is highly mobile but becomes less mobile at 3 months and thicker and immobile after 6 months. The false lumen degenerates and becomes aneurysmal over time. The maximum aortic diameter increases from 39 to 43 mm in the first 6 months (annualized growth, 8 mm/y) and after 9 years becomes 55 mm (annualized growth, 1 mm/y from 6 months–9 years). False lumen thrombus (Thr.) is evident in years 8 and 9.

into false lumen pressure, wall tension, and growth, we may not be able to synthesize a reliable prediction tool that can be clinically tested. Second, only by understanding the interaction of morphology, hemodynamics, and biomechanics will we be adequately equipped to anticipate the effect of interventions on these parameters, which control the long-term fate of the false lumen and thus patient outcome. A broader interdisciplinary approach to the conundrum of the false lumen may help to develop novel therapies.

New insights are currently emerging from the combination of imaging data (3-dimensional [3D] and 4-dimensional morphological data from CT,$^{30}$,$^{59}$,$^{60}$ flow data from magnetic resonance imaging [MRI]$^{61}$), computer simulations (computational fluid dynamics,$^{62}$ fluid-structure interaction$^{9}$,$^{10}$,$^{63}$), bench-top and in vitro phantom studies,$^{64}$,$^{65}$ biomechanical bench testing,$^{66}$ and numerical modeling of aortic wall constituents,$^{66}$⁻$^{68}$ as well as from the field of mechanobiology.$^{11}$,$^{69}$ A graphical synopsis of factors contributing to false lumen dilatation is shown in Figure 4. The key points are as follows:

$\bullet$ The outer wall of the false lumen is a load-bearing structure derived from the aortic adventia left intact after the initial delamination of the intima and variable amounts of the media layer of the aortic wall.

$\bullet$ Restoration of false lumen wall strength and homeostasis is maintained by advential myoblasts/fibroblasts, which are sensitive to changes in wall tension (mechanosensing), responding with proliferation and increased synthesis and crosslinking of collagen. This is noticed at late surgical

intervention as a strong, leathery thickening of the advential layer.

$\bullet$ Even a marginally inadequate tissue response to wall tension can enter a vicious cycle in which any increase in false lumen diameter proportionally translates into an ever-increasing wall tension, resulting in continuous growth of aortic diameters over time.

* Once the restorative capabilities are exhausted and the wall tension exceeds the tensile strength, structural failure and aortic rupture ensue. This occurs with increasing frequency at maximum aortic diameters >55 to 60 mm.

$\bullet$ The wall tension of the false lumen is not only determined by its thickness and geometry (or its clinical proxy, the maximum aortic diameter) but is also directly proportional to the hydrostatic pressure in the false lumen.

$\bullet$ The false lumen pressure is a function of true lumen pressure, modulated by blood flow alterations specific to morphological dissection features. Although the systolic pressure is always equal or higher in the true lumen, an uninhibited inflow into the false lumen (enabled by a large enough primary entry tear), combined with high outflow resistance from the false lumen, results in a reversal of the pressure gradients in diastole. Thus, the diastolic and mean pressures can be higher in the false lumen than in the true lumen.

$\bullet$ False lumen outflow resistance is related to the number of branch vessels draining the false

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 Schematic illustrates the complex interplay between morphological features derived from imaging, with hemodynamic, biomechanical, and mechanobiological factors leading to false lumen degeneration and aneurysm formation and ultimately rupture in chronic aortic dissection. See text for details. CFD/FSI indicates computational fluid dynamics/fluid structure interaction; ECM, extracellular matrix; FL, false lumen; PIT, primary entry tear; and TL, true lumen.

lumen (more draining branches decrease resistance) and to the number, size, and location of communications between the true and false lumens across the dissection flap (fenestrations, re-entry tears).

$\bullet$ The dissection membrane also modulates the pressure gradients between true and false lumens. A mobile flap decreases and a stiff flap augments the pressure differences between the true lumen and the false lumen.

MANAGEMENT OF CHRONIC AORTIC DISSECTION

Watchful Waiting

The mainstay of management of chronic aortic dissection is (1) antihypertensive therapy, including anti-impulse therapy with β-blockade and afterload reduction; (2) life-long surveillance with imaging; and (3) timely repair once the dissected aorta becomes significantly aneurysmal.$^{377,70}$

Anti-impulse therapy was pioneered by Wheat et al$^{71}$ in 1965 to prevent dissection progression in the most acute phase. The effectiveness of combination β-blocker and afterload reducing drugs treatment is unquestioned in both the acute and chronic phases of aortic dissection.$^{72}$ It is important to note that unopposed afterload reduction can lead to unwanted reflex tachycardia.

The rationale for the traditional “watchful waiting” strategy, conceived in the pre-endovascular era, is based on the need to balance the expected morbidity and mortality of preemptive open surgical repair against the risk of fatal aortic rupture. Currently accepted size thresholds were established from the 1997 landmark work of Cody and colleagues$^{46}$ from Yale University demonstrating rapidly increased risk of rupture once the aneurysmal aorta exceeds 6 cm (Supplemental Figure 2). The morbidity and mortality associated with contemporary surgical and endovascular repair are evolving; however, and the optimal treatment and timing for intervention in patients with chronic aortic dissection are becoming less certain.

Current guidelines, published between 2010 and 2017, consistently recommend intervention in patients with aneurysms >6.0 cm (Class I), with TEVAR to be considered in high-risk patients or nonsurgical candidates (Class IIa).$^{37,77,0,73}$ Open surgical repair is recommended in patients with connective tissue disease with an aneurysm diameter of 5.0 to 5.5 cm (Class I or IIa). TEVAR may be considered at that same 5.5-cm-diameter threshold as a Class IIb indication in more recent guidelines.$^{37,77}$ Of note, all pertinent guidelines acknowledge the poor quality of evidence for TEVAR recommendations in patients with chronic dissection and the lack of better evidence-based risk stratification and stress the need for individualized decision-making, ideally by a multidisciplinary team of experts.$^{37,70,73,76}$

The time intervals suggested for surveillance imaging in patients with chronic aortic dissection vary across guidelines and should be tailored for individual patients.$^{377,73,75,76}$ Considering the natural course and reported growth rates of the dissected aorta,$^{46,51,77}$ several reasonable follow-up regimens have been proposed for different treatment groups, preferably beginning with a baseline predischarge scan. After surgical repair, patients could be followed up after 6 and 12 months and annually thereafter. If a moderate-sized aneurysm remains relatively stable over time, subsequent longer follow-up intervals of 1.5 to 3 years are reasonable.$^{70}$ In medically managed uncomplicated type B dissection, 1 additional earlier scan, for example, at 3 months, may reveal important changes occurring in the subacute phase, when the dissected aorta remains amenable to early TEVAR. Earlier follow-up imaging at 30 days is sometimes recommended to identify potential early complications, followed by routine 6-month and 12-month follow-up.$^{377,73,75,76}$ Continued annual imaging is suggested thereafter, even if the aorta stabilizes after TEVAR. If growth or other complications are detected, shorter follow-up intervals may be required in all treatment groups.$^{70}$ Eventually, most patients with chronic aortic dissection develop substantial aortic dilatation, especially in the proximal descend-ing aorta, just beyond the left subclavian artery. These patients can be operated on safely with either open aortic replacement or endovascular therapy, depending on anatomy, age, and connective tissue disorder diagnosis.$^{23}$

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Surgical Treatment of Chronic Aortic Dissection

Open surgical repair remains the dominant method of managing chronic aneurysmal thoracoabdominal aortic dissections given (1) the limitations of current endovascular techniques, including adequacy of landing zones, the noncompliant dissection flap, and the uncertain durability of TEVAR, and (2) the beneficial impact that advances in circulation management, cerebrospinal fluid drainage, neurocerebral monitoring, and peri-operative management protocols have had on surgical outcomes.

Variability in the natural history of chronic descending aortic dissections demands careful monitoring by cardiovascular surgeons as part of a multidisciplinary team including vascular surgeons, cardiologists, and radiologists with interest and expertise in the management of aortic pathology. Acute ascending aortic dissections, despite proximal repair, often incur residual distal arch or descending and thoracoabdominal aortic dissections. Despite similarities to chronic type B aortic dissections, residual type A dissections often have different implications with respect to managing the aortic arch.

Indications for open operative intervention in uncomplicated chronic aortic dissections hinge primarily on aortic caliber, pathogenesis, and occasionally symptoms. Asymptomatic chronic thoracic and thoracoabdominal aortic dissections with a maximal orthogonal aortic diameter of 6.0 cm in patients without connective tissue disease warrant repair.$^{37,46,70}$ Rapid growth rate also may be an indication for repair. Patients with connective tissue diseases and those with a family history warrant more careful consideration and may warrant earlier intervention (diameter of 5.0–5.5 cm).$^{78,79}$Griepc and colleagues$^{80}$ have used a formula that predicts risk according to aneurysm size, age, and the presence of comorbidities such as renal insufficiency and emphysema.$^{56}$ Operative morbidity risk with repair of aneurysmal chronic descending and thoracoabdominal aortic dissections is substantial and potentially includes respiratory insufficiency, renal failure, myocardial infarction, stroke, left vocal cord paralysis, wound infections, and paraplegia. The relative risk of complications imparted by chronic dissection in the context of thoracoabdominal aortic aneurysm replacement has not been distinctly determined by any of the large series. In the largest series (3309 cases) of thoracoabdominal aortic aneurysm repair by Coselli et al,$^{81}$ 36% of cases were operated on for chronic aortic dissection: Operative mortality was 7.5%; dialysis dependence rate was 5.7%; and paraplegia rate was 2.9%. Smaller recent reports on outcomes in this specific patient population are similar with mortality rates ranging from 5.8% to 11%.$^{82-89}$ There remains no consensus among the large thoracic aortic centers around the world as to the optimal operative repair strategy for

chronic aneurysmal thoracoabdominal aortic disease. Limiting the repair to the aneurysmal segment rather than the entire dissected aorta reduces the risk of complications and paraplegia, but several techniques have been successful in delivering acceptable morbidity and mortality for this difficult problem. The 2 centers with the lowest reported mortality for thoracoabdominal aortic aneurysm repair in the context of chronic section have used deep hypothermic circulatory arrest for their technique.$^{83,90}$

Endovascular Therapy

Open surgical repair may be too morbid for some patients with chronic dissection and is often postponed for too long.$^{88,91}$ TEVAR provides another mechanical treatment option that has been increasingly used because of the low acute risk compared with open repair and the potential to reduce aortic mortality and reoperations compared with medical therapy.$^{92,93}$ However, TEVAR faces anatomic and morphological limitations to successfully treating this disease, particularly in the chronic stage.$^{94-97}$

A TEVAR-based strategy seeks to seal intimal entry tears with device fabric and to expand the true lumen by outward radial force of the stents. In patients with chronic aortic dissection and aneurysm, covering entry tears is an important treatment objective to promote thrombosis and false lumen remodeling.$^{97}$ A patent false lumen has been associated with decreased survival and increased risk of reintervention.$^{98}$ TEVAR of chronic dissection may promote false lumen thrombosis at a variable rate over time. It has been shown, however, that thrombosis needs to be complete to reverse the natural history of disease.$^{96,97}$

In most patients with type B aortic dissection, the proximal entry tear can be covered with an endograft. Coverage of the left subclavian artery is often necessary to achieve an adequate proximal landing zone. Patients with dissections limited to the descending thoracic aorta (DeBakey type IIIA) often exhibit an adequate landing zone in the distal descending thoracic aorta.$^{41,99}$ Unfortunately, most dissections extend across the visceral branch origins. Re-entry tears and fenestrations of the dissection flap within the abdominal aorta frequently maintain false lumen perfusion and pressurization. Increased number and size of distal re-entry tears and false lumen origin of branch vessels are associated with persistent false lumen flow.$^{97,100}$

Several strategies can be used to facilitate a distal seal of an excluded false lumen aneurysm to prevent retrograde filling such as percutaneous “cheese-wire” flap fenestration, balloon septum rupture (Knickerbocker technique), laser aortic septotomy, or placement of coils of plugs (candy plug technique) for false lumen emboliization (Supplemental Figure 3). Additional endovascular therapies may require the use of bare stents to expand

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the true lumen with or without ballooning or the use of investigational or homemade branched devices.$^{101-111}$

Role of Imaging for TEVAR Planning and Follow-Up in Chronic Dissection

Endovascular treatment planning is typically based on preoperative CT angiography (CTA). A fundamental requirement for successful TEVAR is an adequate device landing zone of healthy aorta of at least 15 mm in length and between 18 and 42 mm in diameter that will allow a parallel lie of the sealing endograft. Predis-charge, assessment of adequate device position, successful coverage of communications and tears, and assessment of branch vessels that can contain re-entry tears is important. Surveillance imaging is critical to mon-itor aortic dimensions, persistent false lumen patency, or thrombosis and any new complications. Adequate imag-ing assessment after TEVAR requires a delayed-phase scan to identify small leaks that slowly fill yet pressurize the false lumen.

Considerations in Patients With Connective Tissue Disease

There is limited information about the best strategy to manage chronic dissections in patients with a genetic predisposition to aortic diseases. Although dissections are more frequent and occur at a younger age in these groups than in the general population, the overall prevalence is low, challenging the design of comparative trials. Most available data come from registries and retrospective studies that have not examined determinants for interventions.

In an analysis of registry data, patients with the Mar-fan syndrome were more likely to have an intervention than medical treatment when presenting with an acute type B dissection.$^{112}$ Although the reason for this was not specifically captured, a possible explanation is that patients with Marfan syndrome tend to have extensive aortic involvement,$^{112,113}$ which may influence the deci-sion. There was no difference in organ malperfusion.

Although endovascular procedures can be lifesaving in the acute setting in these patients, open surgery is preferred for chronic dissections because of the concern for retrograde dissection proximally, early graft failure attributable to tensile forces of the graft in an abnormal aortic wall, and increased need for reinterventions after endovascular repair.$^{114}$

Information on chronic dissections in Ehlers-Danlos syndrome (vascular type) is even scarcer. A multicenter cross-sectional retrospective study of 86 patients$^{115}$ reported 17 with aortic pathology treated by medical management; thus, the authors recommended intervention only for distinct complications. Open surgery is preferred over an endovascular approach on the basis of the risk of erosion or perforation at the landing

zones of the endograft resulting from the fragility of the aortic wall.$^{115}$⁻$^{117}$

IMAGING TECHNIQUE

Computed Tomography

CTA is the most commonly used modality for imaging of patients with acute and chronic aortic dissection.$^{118-120}$ State-of-the-art CT scanners are widely available and capable of acquiring high-resolution volumetric data sets that can be reformatted into a wide range of 2-dimensional and 3D angiographic images.

A typical imaging protocol includes an optional noncontrast scan for identification of surgical grafts and high-attenuation foci that can mimic pseudo-neurysm, followed by a 50- to 150-mL contrast medium-enhanced angiographic acquisition. Additional delayed-phase scans are required in post-TEVAR patients to assess for endoaks and can help distinguish slow flow-related unenhanced regions in the false lumen from thrombus. Scan times for each acquisition range between 5 and 20 seconds. Measurements of the ascending aorta are more reliable when electrocardiographic gating is used to suppress cardiac pulsation artifacts,$^{121}$ although the scan time of many modern scanners is short enough to render electrocardiographic gating less necessary. If retrospective electrocardiographic gating is used, CT images can be reconstructed and viewed over the entire cardiac cycle, adding a fourth dimension to CTA.

The effective radiation dose from a single arterial phase CT scan is ≈ 2 mSv (range, 2–20 mSv) and from a 3-phase scan is ≈25 mSv (range, 3–60 mSv).$^{122,123}$ Even in the setting of lifelong surveillance with annual CT scans, the estimated excess risk of cancer attributable to CT radiation is low, between 0.43% and 0.65% for patients in their early 50s and even less in older individuals.$^{122,124}$ For comparison, the lifetime risk of cancer is almost 100 times greater at 44%.$^{125}$ The known benefits of a clinically indicated CT scan in the typical age group of patients with chronic dissection almost certainly exceed the uncertainties and theoretical risks of imaging-related radiation exposure.

Magnetic Resonance Imaging

MRI is an accepted alternative to CTA for the assessment of patients with chronic aortic dissection.$^{126,127}$ Advantages of MRI include lack of ionizing radiation,$^{70}$ which may be a particularly important consideration in young individuals such as patients with Marfan syndrome in their 20s or 30s with near-normal life expectancy, especially before the aorta becomes dissected, substantially aneurysmal after dissection, or difficult to assess after serial interventions. Disadvantages of

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MRI compared with CT include a longer scan duration, lower spatial resolution, artifacts from implanted devices such as endgrafts or mechanical heart valves, and potential contraindications such as certain metallic implants.

A typical MRI protocol includes multiple sequences. Contrast-enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents provides high-quality 3D data sets. Like CTA, MRA allows multiplanar evaluation to obtain orthogonal measurements. Recent advances in noncontrast MRA techniques have made this a viable alternative in patients with contra-indications to gadolinium-based or iodinated contrast agents.$^{128}$ The addition of phase-contrast imaging allows the assessment of blood flow and false lumen thrombosis.$^{129}$

Four-dimensional flow MRI is an emerging technique that allows exquisite characterization of altered flow dynamics in both true and false lumens and quantification of parameters such as wall shear stress, which may have prognostic value.$^{130-133}$ Given the potential role of inflammation in the progression of aortic aneurysms, the recent integration of hybrid positron emission tomography/MRI systems may provide another avenue for simultaneous assessment of anatomic, physiological, and molecular imaging biomarkers.$^{134}$

Echocardiography

Transthoracic echocardiography (TTE) is commonly performed in patients with chronic aortic dissection with concomitant dilatation of the unrepaired aortic root. In select patients, TTE and transesophageal echocardiogram (TEE) also can be useful to evaluate the dissection flap,$^{37}$ to demonstrate communications between the true and false lumen, and to assess blood flow versus thrombus in the false lumen. TTE and TEE do not require contrast agents or ionizing radiation. The disadvantages of echocardiography are that not all aortic segments can be interrogated and TEE requires sedation.

TTE is noninvasive and allows evaluation of the aortic valve, root, and ascending aorta at each follow-up. In some patients, the arch can be visualized through the suprasternal view. The descending aorta is only occasionally visualized.$^{135}$

TEE allows visualization of the aortic arch but requires sedation and has a blind spot in the distal ascending aorta caused by the interposition of the right tracheobronchial angle.$^{135}$ For acute dissections, TEE has a high sensitivity (86%–100%) and specificity (90%–100%) compared with CTA.$^{136}$ In chronic dis-sections, 3D TEE and 2-dimensional TEE have been compared with CT and were equivalent in locating and measuring the entry tear size, and they were better at detecting secondary tears.$^{137}$

MEASUREMENT PRINCIPLES

The quintessential information sought from imaging studies in patients with chronic aortic dissections is aortic caliber. The maximum aortic diameter is strongly associated with the risk of aortic rupture and currently remains the predominant parameter for surgical decision-making.$^{37,46,70,73-76}$ Measurements of adjacent segments as potential landing zones, separate diameter measurements for true and false lumen, and access vessel size are also important for determining anatomic eligibility and treatment planning for endovascular repair.$^{138}$

Despite its importance and the large number of measurements obtained every day in hundreds of patients with chronic aortic dissection, few specifics on how to perform and compare measurements of the dissected aorta can be found in the literature.$^{119}$,$^{120}$

Definition of Aortic Diameters

The aorta is a curved, tubular structure, often with a non-circular cross section, tapering from proximal to distal, while giving off multiple branch vessels. Aortic diameters refer to the cross-sectional distances obtained in a plane that is orthogonal to the aortic flow channel, often represented as its medial axis$^{139}$ or aortic centerline. On a given orthogonal cross section, aortic diameters are expressed as the diameters of the long (major) axis and the short (minor) axis, respectively (Figure 5). The maximum aortic diameter is the largest of all major axis diameters on any of the aortic cross sections along the aorta.

In addition to the maximum aortic diameter, aortic measurements typically include diameters at predefined landmarks along the aorta such as the aortic root at the annulus, at the sinuses of Valsalva, and sinotubular junction, as well as select locations in the ascending aorta, in the aortic arch, and along the descending thoracoabdominal aorta.$^{140,141}$

Measurement Technique

There is unanimous agreement that aortic diameters should be measured perpendicular to the aortic long axis.$^{142,143}$ CTA and MRA data are 3D volumes consisting of stacks of narrow-spaced 2-dimensional slices. Obtaining the appropriate measurement plane in CTA and MRA therefore requires reformatting the data into so-called double-oblique images or multiplanar reformations (MPRs).

MPRs can be obtained either manually or with the assistance of (semi)automatically generated aortic centerlines. With the centerline method, perpendicular MPRs can easily be created, and distance measurements can be obtained along the aortic axis. The aorta can also be unfolded along its centerline as a straightened- or a

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 Maximum diameter is measured on double-oblique reformations oriented orthogonal to the aortic flow channel. Note the remarkable difference between the long-axis diameters between the transverse images (47 mm vs 54 mm). Major and minor axis diameters include the luminal thrombus if present. Ann indicates aortic annulus; bif, bifurcation; Darc, distal arch; Ddes, distal descending aorta; MidAsc, middle ascending aorta; Parc, proximal arch; Pdes, proximal descending aorta; SOV, sinus of Valsalva; and STJ, sinotubular junction.

curved-planar reformation, which also facilitates length measurements, in addition to diameters.$^{144}$

In patients with chronic dissection, selecting the best MPR orientation becomes more difficult as the false lumen becomes larger and approaches the surgical size threshold. Asymmetry and stark differences in contrast enhancement between the true and false lumen, with or without the presence of false lumen mural thrombus, often preclude the use of the centerline method at this stage, whereas increasing tortuosity and kinking caused by aortic elongation pose a formidable challenge to manually selecting the best MPR orientation, even for experienced users. Selection of MPR location and orientation is likely the largest source of measurement uncertainty and discrepancies in patients with chronic dissection and false lumen aneurysms.

Aortic Measurements on Transverse Images

Axial images are commonly reviewed to obtain a first impression and approximate size of a patient's aorta. It cannot be overstated, however, that transverse (axial) images are unsuitable to accurately determine the maximum aortic diameter.$^{145}$ Incorrectly using the largest dimension of an oblong aortic cross section on axial images has been shown to overestimate vessel size by up to 6 to 7 mm on both CT and MRA.$^{146,147}$ If an aortic

diameter must be measured on axial images (eg, in an emergency or without CT data or 3D viewing capability), the short-axis diameter is a closer approximation of the true diameter and should be recorded.$^{148,149}$ However, this approach may underestimate the true maximum aortic diameter in patients with an ellipse-shaped aneurysm.$^{150,151}$ Viewing of coronal or sagittal images mitigates but does not eliminate this problem.

Reproducibility and Discrepancies

Although most of the literature and guidelines on imaging-based measurements of the aorta focus on the aortic root and thoracic or abdominal aortic aneurysms, several technical limitations and uncertainties also apply to chronic aortic dissection.

Cardiac Phase and Electrocardiographic Gating

Although echocardiographic diameter measurements are typically obtained in middiastole,$^{143}$ there are no consistent recommendations for CT and MRI across multimodality guidelines with respect to the most appropriate cardiac phase for aortic assessment.$^{143}$ Both the 2010 American College of Cardiology Foundation/American Heart Association guidelines and the 2020 International Society for Magnetic Resonance in Medicine recommendations suggest the use of electrocardiographic gating triggered to end diastole for the assessment of the aortic root.$^{70}$,$^{140}$

In chronic dissection, this is most relevant for patients with unrepaired root aneurysms. Aortic pulsation is typically small (1–2 mm) in patients with noncompliant aneurysmal aortas. The main reason for electrocardiographic gating is not to capture maximum dilatation (which would be during the short systolic phase) but to suppress the more pronounced translational motion of the aortic root and proximal ascending aorta attributable to ventricular contraction. Thus, diastolic reconstructions are favored for ECG-gated CT as well. Gating is a prerequisite for accurate aortic root and proximal ascending measurements but is not critical for the distal aorta.

Inclusion or Exclusion of the Aortic Wall

There is currently no clear consensus on whether the aortic wall should be included in aortic diameter measurements, although the difference may be several millimeters, particularly if there is atherosclerotic disease or mural thrombus.$^{142,152}$

For TTE measurements of the aortic root, the 2010 American College of Cardiology Foundation/American Heart Association guidelines recommend using the internal diameter.$^{70}$ The American Society of Echocardiography recommends measurement of the aortic root from the leading edge of the anterior wall to the leading edge of the posterior wall (leading edge to leading edge) on a parasternal long-axis view, thus including half of the

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aortic wall.$^{153}$ Most of the normative data on aortic size in the literature were obtained with this technique, and this convention is used clinically in many centers.$^{154-156}$ A 2015 multisociety expert consensus statement recommends maintaining the use of the leading edge-to-leading edge technique because of the greater reproducibility of this approach.$^{143}$

For CT and MRI, there also is no clear consensus.$^{157}$ The 2010 American College of Cardiology Foundation/American Heart Association guidelines recommend measurement of aortic diameters between external surfaces on CT and MRI (outer wall to outer wall) given that lumen size may not reflect the true size of the aorta in the presence of intra-aortic thrombus, atheroma, aortic wall inflammation, or dissection.$^{70,158}$ The outer wall technique also can be applied to noncontrast CT. In clinical practice, however, and in most research studies, the internal cross-sectional diameter is reported.$^{152,159}$ The 2020 International Society for Magnetic Resonance in Medicine guidelines also recommend inner lumen-to-inner lumen measurements of the aorta on MRI.$^{140}$

Patients with aortic dissection have 2 flow channels. The outer wall of the true lumen usually has normal wall thickness ($\approx 1$ mm), which is simply too thin to be resolved as a separate structure even on a high-quality CTA ($\approx 1-mm^3$ voxel dimensions). The distinction between inner and outer contours is thus most. The outer wall of the false lumen is initially even thinner and cannot be resolved either until it becomes >1 mm thick. The high-contrast interface between lumen and surrounding tissue is therefore a reasonable representation of diameter and can be detected automatically. Once mural thrombus occurs and obscures the interface between the (now thrombased) lumen and the inner border of the aortic wall, it becomes necessary to use the outer aortic contour as a landmark. The resulting “error” of including 1 of the 2 walls in the total measurement is probably small, 1 to 2 mm.

A final example of inconsistency with respect to inclusion versus exclusion of the aortic wall can be found in TEVAR device sizing guidelines. Cook Medical (Bloomington, IN) bases its recommendations for the Zenith Alpha Thoracic Endovascular Graft on outer wall-to-outer wall dimensions,$^{160}$ whereas WL. Gore (Flagstaff, AZ) recommends sizing of its Conformable TAG Thoracic Endoprostesis on the flow lumen (including thrombus), not the vessel wall.$^{161}$

Differences Within and Between Imaging Modalities

Most studies comparing 2-dimensional TTE with CT and MRI found that TTE significantly underestimates aortic root diameters compared with CT$^{162}$⁻$^{164}$ and MRI,$^{163}$⁻$^{166}$ likely related to off-axis image acquisition and root asymmetry. On the other hand, 3D TTE correlates well with CT.$^{165}$ Several studies also have demonstrated that abdominal ultrasound systematically underestimates the

size of abdominal aortic aneurysms by ≈1 to 3 mm compared with CT.$^{167-171}$

In the nondissected thoracic and abdominal aorta, the agreement between diameter measurements obtained with CTA and MRA is good when the same analysis technique is used,$^{168-171}$ and interobserver agreement is excellent.$^{163,164,172}$ No such data are available for chronically dissected distal aortic segments, however. It is reasonable to assume that agreement is less, perhaps more similar to the interobserver and intraobserver variability of CT for abdominal aortic aneurysms, reported at ≈5 and 3 mm, respectively.$^{168-170}$

Implications for Serial Measurements

There is broad consensus that an identical imaging technique be used for serial aortic imaging.$^{37,70,143}$ Given the degree of variability in measurements, a recent expert consensus statement recommended caution in interpreting apparent changes in aortic diameter ≤3 mm by ECG-gated CT and ≤5 mm by nongated CT.$^{143}$ Aortic growth estimates based on small apparent diameter increases over short time intervals (≤6 months) also should be treated with caution given the potential implication for surgical repair.

This represents a considerable degree of uncertainty given the clinical implications for patients with chronic aortic dissection. It is currently unknown whether including details of the measurement technique (eg, gating, inclusion of wall, orientation of measurement plane), as proposed by Freeman et al,$^{152}$ in the radiology report improves interpretation of imaging results by the treating physician. Selecting identical anatomy and measurement planes may be the most important steps to reduce overall measurement discrepancies in patients with chronic dissections and aneurysms; however, this has not been formally studied.

False Lumen Measurements

Separate measurements of true and false lumen diameter, area, or outer aortic wall circumference have been used in research but are not routinely obtained in patients with aortic dissection.$^{59,119}$ Diameter and area measurements (but not circumference) are affected by the deformation of the dissection flap over the cardiac cycle.$^{30,59}$ A proximal descending aorta false lumen diameter >2.2 cm has been associated with late complications in patients with uncomplicated type B aortic dissections.$^{173}$ Volumetric measurement techniques may be more reliable for documenting small changes over time and have been used to define positive and negative remodeling in device trials.$^{96,174}$

SURVEILLANCE IMAGING

Providing technically accurate aortic measurements in patients with chronic aortic dissections is a prerequisite

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 Figure 6. Serial imaging: spatial alignment of orthogonal measurement planes.

Baseline (left) and 3-month, 6-month, and 12-month (right) follow-up computed tomography scan of a patients with type A dissection treated with ascending aortic repair. Accurate growth measurement requires double-oblique images to be obtained at the same location and orientation along the aorta. A indicates anterior; F, feet; H, head; L, left; P, posterior; and R, right.

but is not nearly enough for adequate surveillance imaging, for which a large number of patients with numerous follow-up studies are routinely encountered.

Comparisons With Priors, Including Older and Outside Imaging

In patients with chronic aortic dissection, it is imperative that each imaging study is carefully compared with priors, including studies done at other facilities.$^{175}$,$^{176}$ Ideally, all prior studies should be reviewed before a therapeutic decision is made.$^{37}$ At a minimum, the most recent prior study and the earliest (baseline) study should be compared with the current study.

Serial Measurements and Comparisons

Serial measurements should always be obtained at the same anatomic location and identical orientation along the aorta, particularly when the diameters approach the intervention threshold. This requires direct side-by-side comparisons of original image data sets, typically done on a 3D workstation, and can be a time-consuming task in patients with elongated and tortuous dissected aortas (Figure 6). It cannot be overemphasized that comparing independently reported measurements without reviewing the actual images is highly unreliable and can lead to spurious aneurysm growth or missing significant enlargement, with potentially serious consequences.

None of the above requirements are easily accommodated within a busy imaging service. First, it is necessary to clearly identify the patients for whom elaborate measurements are requested. The full gamut of necessary measurements and documentation is often too time consuming to be routinely carried out by the interpreting physician, notably if similar measurements also need to be performed on prior images at the time of interpretation. Prior images are not always easily available, and often no mechanism to review, analyze and report outside imaging studies exists.

These predicaments can be overcome by building a dedicated surveillance program made up of agreed-on measurement, comparison, and reporting protocols at its core. Specific recommendations for structuring and implementing a surveillance program are currently not available, and although there is little doubt that better standardization has benefits, we do not have any evidence that implementation of a surveillance program improves outcomes. The initial investment of time, effort, and resources to build the logistical framework is considerable and may be warranted only for aortic centers specialized in the lifelong care for patients with chronic dissection and other aortic diseases.

Imaging Surveillance Program

At the core of any dedicated aortic imaging surveillance program is the standardization of the measurement protocol and the development of a mechanism

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 A, For each baseline and follow-up imaging study, orthogonal aortic diameter measurements are entered into a spreadsheet or database. Note that in this patient the maximum diameter is approximately halfway between 2 standard aortic landmarks, the proximal (Pdes) and distal (Ddes) descending thoracic aorta. B, Diameters (y axis) are also plotted graphically against anatomic landmarks along the aorta (x axis). Time is color coded, with the baseline study plotted in green, the second-to-last study in blue, and the latest study in red.

how to perform, store, and retrieve comparison measurements (including for outside studies). This requires that a patient's measurements are obtained at 1 point in time and are available at all subsequent visits. This way, a patient's surveillance record only needs to be updated with the latest, carefully obtained side-by-side measurements, except if a patient enters the system at a later stage or at the time of program initiation. Reporting standards also need to be agreed on, including how the pertinent information can be incorporated into or added to the radiological report and the patient's medical record. Additional logistics related to prioritizing measurements for clinic visits, ordering and billing of measurements on outside studies, and quality assurance need to be developed in close collaboration between radiologists, cardiothoracic and vascular surgeons, cardiologists, and vascular specialists and their respective teams. Last, close interaction between clinical and postprocessing teams to reconcile any discrepancies and to improve the system is important for maintaining a vital service.

The execution of the core tasks is best implemented in a 3D laboratory or equivalent where trained

technologists perform measurements with consistent quality. A sample measurement protocol is provided in Supplemental Figure 4. Most large institutions housing an aortic center most likely also have a 3D laboratory or at least the functionality of such a laboratory in their imaging departments.

Reporting and Visualization

The key information, that is, the validated diameter measurements compared with corresponding prior measurements, is best reported in a table rather than in text format augmented by a graphical display that better visualizes the information for physicians, staff, and patients. A simple example is shown in Figure 7, in which aortic diameter measurements at different time points are listed in a table (a simple spreadsheet suffices) and plotted graphically.

An infinite range of alternative methods can be used to visualize the relevant information, including interactive tools switching between simple diameter plots and displays emphasizing the time axis.$^{177}$ Several symbols or cartoon representations for differently

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treatment segments (surgical grafts, endografts) also can be displayed.$^{178}$ Currently, these techniques are custom made and developed out of necessity at academic institutions, but similar to other applications such as planning for abdominal endovascular aortic repair or transcatheter aortic valve replacement, commercial tools are likely to become available eventually.

RISK STRATIFICATION AND NEW DEVELOPMENTS

After decades of management choices limited to watchful waiting followed by elective open repair in the chronic phase, new treatment options during the acute or subacute phase have become available that may reduce the risk of late complications in patients with aortic dissection.$^{95,179,180}$ Patient selection and choice of the best therapy remain a challenge, however. For instance, identifying patients who are most likely to benefit from preventive TEVAR in type B dissection requires the ability to predict the time course of the false lumen dilatation. Likewise, considering alternative treatment options requires the ability to forecast the effect of each intervention on the fate of a patient's aorta.

Several attempts to improve risk stratification in patients with aortic dissection have been made over the past years. A major focus of interest and ongoing matter of debate is risk stratification of patients with uncomplicated type B dissection. Initial strides toward predicting and simulating the effects of interventions in patients with aortic dissection have also been reported.

Predicting Late Adverse Events in Uncomplicated Type B Dissections

Patients with initially uncomplicated type B aortic dissection have excellent early survival but a 20% to 50% risk of late adverse events.$^{55,56,181}$ Although early TEVAR may prevent or at least delay late complications, only a subset of high-risk patients are likely to benefit from the procedure, which is not without its own risks.$^{182-184}$ Several studies have sought to identify morphological predictors of aneurysm growth and late adverse events to better risk-stratify these patients.

In a systematic review of 51 original studies, Spinelli and colleagues$^{59}$ analyzed the consistency of reported morphological predictors of adverse events in patients with uncomplicated type B dissections. Of the wide range of published morphological predictors, only 2 had a consistent effect across the literature: (1) Aortic diameter at presentation was consistently associated with adverse events, and (2) complete false lumen thrombosis always had a protective role. Inconsistent

and even conflicting results were reported for other investigated predictors, including false lumen diameter and length; false lumen location (lesser or greater curvature of the aorta); number, size, and location of the primary entry tear; branch vessel involvement; and partial false lumen thrombosis.

The reported inconsistency of morphological features to predict adverse events might be explained by the fact that candidate predictors were analyzed as isolated, unconnected features, not in the context of our evolving understanding of the pathophysiology of aortic dissection in which features are hemodynamically linked. For instance, the effect of the size of the primary entry tear (allowing false lumen inflow) cannot be interpreted meaningfully without knowledge of the false lumen drainage (outflow resistance). Only 1 small study of 83 patients with uncomplicated type B dissection combined 4 independent morphological and 1 clinical predictor into a single prediction model for late adverse events, and 1 of the independent predictors was false lumen drainage (outflow).$^{30}$ External validation and more comprehensive analyses of aggregated dissection features in larger cohorts are needed. A prerequisite is the development of automated tools to extract the potentially important features because manual segmentation is prohibitively time consuming and unreliable.$^{185}$

Last, it is important to recognize that some of the morphological predictors such as maximum diameter, the relative proportion of the outer aortic wall circumference encompassing the false lumen, and the occurrence of partial false lumen thrombus change over time. Those changes over time (eg, growth) on serial CT imaging have predictive power of their own.$^{186}$ Hence, an ideal prediction model for patients with uncomplicated type B dissection not only would predict the risk at baseline (eg, at time of hospital discharge) but also would allow the risk estimate to be updated with new clinical and morphological information at every follow-up encounter. Currently, such models do not exist.

Predicting the Fate of the False Lumen After Surgical or Endovascular Intervention

In experienced hands, surgical repair of the ascending aorta can be safely extended into the aortic arch or beyond with placement of a conventional or “frozen” elephant trunk into the descending thoracic aorta.$^{179,180}$ Hybrid and endovascular treatment options are also evolving. Ascending repair can be combined with antegrade placement of a descending aortic endograft$^{187}$ or with a dedicated partially uncovered aortic arch hybrid graft (Ascyrus Medical Dissection Stent) at the time of operation.$^{188}$ Covered endografts also can be combined with uncovered devices, for example, in the provisional

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extension to induce complete attachment approach,$^{189}$ in acute type B aortic dissection.

Although the long-term effect of these interventions will not be known for many years, imaging and simulations can help anticipate early markers of success, notably the induction of false lumen thrombosis. Computer simulations developed at the Imperial College London have shown that the location of thrombus formation can be predicted from patient-specific dissection morphology before and after placement of, for example, an endograft.$^{190,191}$

New Developments: Machine Learning

The potential of using the massive amounts of accumulated radiological data to predict rupture and to determine the best timing for intervention was recognized many years ago.$^{70}$ Except for maximum aortic diameter, however, the importance of many candidate morphological features remains uncertain, and manual annotation (segmentation) of imaging features in patients with aortic dissection is difficult and prohibitively time consuming for clinical application.

New machine-learning algorithms may overcome these limitations. Several dissection features such as the true and false lumen and diameter measurements have been successfully identified with deep-learning algorithms.$^{185,192}$ Aortic landmarks have been detected with a range of techniques, including deep-reinforcement learning.$^{193}$ Random forest classification methods have been used to investigate the risk of developing type A dissection according to CT and clinical data.$^{194}$ Aneurysm growth also has been predicted with encouraging accuracy in abdominal aortic aneurysms with a set of benchmark learning techniques.$^{195}$

Although immensely promising, these initial results from rapidly evolving machine-learning applications for segmentation, classification, and risk prediction in aortic dissection are still a far cry from clinical-grade, robust applications. Validating these new tools with large enough well-curated and expert-annotated imaging databases with clinical outcomes is still required but difficult to accomplish in patients with a relatively rare, anatomically complex chronic disease.

SUMMARY

Chronic aortic dissection is an underrecognized cardiovascular disease and growing health care burden. Imaging and image processing will continue to play a pivotal role in surveillance and clinical decision-making in these patients, as long as accurate and standardized measurements of aortic dimensions over time are provided.

There is a great need for additional research into the epidemiology and natural history, pathophysiology, management, and prediction of outcomes in patients

|Epidemiology and economic impact| |---| |The actual prevalence of patients living with chronic aortic dissection is currently unknown.| |The cumulative lifetime expenses for long-term specialty care and interventions in patients with chronic dissection have not been adequately appraised.| |Natural history and pathophysiology| |The natural history and the effect of evolving therapies on outcomes in patients with chronic dissection are incompletely established. Prospec-tive, multicenter registries with concurrent recording of clinical and imag-ing data are needed.| |Sex-and racial differences in false lumen growth over time and in long-term outcomes and prognosis have not been investigated in patients with chronic dissection, despite known differences in incidence age, clinical presentation, and short-term outcomes in women.| |The hemodynamics and mechanobiology of the dissected aortic wall and their interplay with progression and complications are incompletely understood.| |The biological, cellular, and molecular processes involved in the repair, progression, and remodeling of affected arteries need to be further inves-tigated.| |Clinical management| |New tools and methods for modeling treatment effects, eg, how different surgical or endovascular techniques affect blood flow, false lumen pres-sure, and the chance of false lumen thrombus formation, are needed.| |Adequate data to establish evidence-based standardization and personal-ization of surveillance intervals are currently lacking.| |Imaging techniques and measurements| |Better tools to facilitate the current manual and semiautomated diameter measurements, including comparison measurements and documentation, are urgently needed.| |New machine-learning tools for fully automated or semiautomated extrac-tion of prognostically relevant features beyond diameters are required.| |Risk prediction and modeling| |Validated prediction models for risk stratification and guidance of treat-ment at the time of the acute event are highly desirable. Ideally, patient risk can be updated at each follow-up interval.| |The best combination of morphological, functional, and clinical param-eters for predicting adverse events has not yet been determined.| |Projecting geometric changes over time is necessary to foresee potential changes in anatomic suitability for endografting over time.|

with chronic aortic dissection to support the ongoing paradigm shift from the prevailing watch-and-wait treatment strategy to an individualized selection of traditional or new surgical, endovascular, or hybrid interventions in the future. Important questions identified by the writing group, intended to serve as an impetus for additional research, are listed in the Table. Given the uncommon nature, unspecified economic impact, and long follow-up needed to study chronic aortic dissection, funding for research is challenging, and significant advances will undoubtedly require interdisciplinary collaboration across a large network of research and clinical centers. High-resolution imaging data, combined with computer simulations, biomechanical modeling, and machine learning, may help answer many of the remaining questions and

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ultimately improve the lives of patients with chronic aortic dissection.

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on September 8, 2021, and the American Heart Association Executive Committee on October 25, 2021. A copy of the document is available at https://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 215-356-2721 or email MeredithEdelman@wolterskluwer.com.

The American Heart Association requests that this document be cited as follows: Fleischmann D, Afifi RO, Casanegra AI, Elefteriades JA, Gleason TG, Hanneman K, Roselli EE, Willemink MJ, Fischbein MP; on behalf of the American Heart Association Council on Cardiovascular Radiology and Intervention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; and Council on Cardiovascular Surgery and Anesthesia. Imaging and surveillance of chronic arctic dissection: a scientific statement from the American Heart Association. Circ Cardiovasc Imaging. 2022;15:e000075. doi: 10.1161/ HCl.0000000000000075

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."

Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the "Copyright Permissions Request Form" appears in the second paragraph (https://www.heart.org/en/about-us/statements-and-policies/copyright-request-form).

Disclosures

Writing Group Disclosures

|Writing group member|Employment|Research grant|Other research support|Speakers' bureau'honoraria|Expert witness|Owner-ship interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Dominik Fleischmann|Stanford University School of Medicine|None|None|None|None|None|None|None| |Michael P. Fischbein|Stanford University School of Medicine|NIH (R01; not related to review)†|None|None|None|None|None|None| |Rana O. Afifi|McGovern Medical School at The University of Texas Health Science Center at Houston. Afiliated with Memorial Hermann Heart & Vascular Institute|None|None|None|None|None|None|None| |Ana I. Casanegra|Mayo Clinic|None|None|None|None|None|None|None| |John A. Elefteriades|Yale University School of Medicine, Aortic Institute at Yale-New Haven Hospital|None|None|None|None|2 Casest|Cool-Spine*|CryoLife*; Terumo/Vascutek*| |Thomas G. Gleason|University of Maryland School of Medicine|None|None|None|None|None|None|Abbott (un-paid)*| |Kate Hanneman|Toronto General Hospital, Peter Munk Cardiac Centre, University Health Network, University of Toronto (Canada)|None|None|None|None|None|None|None| |Eric E. Roselli|Cleveland Clinic Heart and Vascular Institute|Cook†; Cryolifet; Gore†; Medtronic†; TerumoAortic† (PI for research grants for all)|None|Cook*; Gore*; TerumoAortic*|None|None|Cryolife*; Gore*; Medtronic*; TerumoAortic*|None| |Martin J. Willemink|Stanford University School of Medicine|None|None|None|None|None|None|None|

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

*Modest.

†Significant.

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Reviewer Disclosures

|Reviewer|Employment|Research grant|Other research support|Speakers' bureau/honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Nicholas S. Burris|University of Michigan|Radiologic Society of North America (active research grant to study hemodynamics in type B dissection using 4D flow MRI)†|None|None|None|None|None|None| |R. Scott McClure|Foothills Medical Centre, University of Calgary (Canada)|None|None|None|None|None|None|None| |Christoph A. Nienaber|The Royal Brompton & Harefield NHS Trust (United Kingdom)|None|None|None|None|None|None|None|

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person's gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

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