Minimum Core Data Elements for Evaluation of Thoracic Aortic Disease.

The expert panel defined a total of 143 core data elements ( Table 2 , Supplemental Table 1 ). To facilitate data entry when resources are limited, investigators can choose to collect a minimum dataset with only core aortic elements (tier 1, 29 elements, Supplemental Table 2 ) or a limited dataset (tier 2, 67 elements, Supplemental Table 3 ) rather than the entire core dataset (tier 3, 125 elements, Supplemental Table 4 ). We also defined an optional set of elements for investigators who wish to collect more precise data on key exposures and outcomes ( Supplemental Table 5 ). Table 2 Core Data Elements for Evaluation of Thoracic Aortic Disease Thoracic Aortic Segments Thoracic Aortic Measurements • Annulus • Sinuses of Valsalva • Sino-tubular junction • Ascending • Arch • Aortic isthmus • Descending • Timing of study • Imaging modality • Location • Perpendicular landmark • Edges • Sinus measurements • Height • Weight Thoracic Aortic Pathologies Blood Pressure Measurements • Timing of diagnosis • Dilation • Aneurysm • Dissection • Penetrating ulcer • Intramural hematoma • Rupture • Coarctation • Patent ductus arteriosus • Aortic valve morphology • Timing of measurement • Clinic blood pressures (>2) • Self-measured blood pressures (>2) • Heart rate • Ambulatory blood pressure • Nocturnal dipping Mental Health and Quality of Life Medication and Environmental Exposures • Anxiety • Depression • Post-traumatic stress • Health-related QoL • Chronic stress • Subjective social status • Adverse childhood • Perceived discrimination • Social isolation • Medication name • Medication dose • Medication frequency • Duration of use • Low-density lipoprotein • HbA1c • INR Reasons for Evaluation of Suspected TAD Genetic Data • Age at initial presentation • Reason: relative • Reason: aortic dissection • Reason: incidental • Reason: examination • Reason: symptoms • Genetic diagnosis of individual • Genetic test result of individual • Genetic test results of relatives • DNA variant and reference sequence • Protein variant and reference sequence • Genetic ancestry Extra-Aortic Features Associated with HTAD Autopsy Data • Pectus anomaly • Skeletal abnormalities • Long limbs • Foot deformities • Premature osteoarthritis • Pneumothorax • Joint hypermobility • Dural ectasia • Skin abnormalities • Eye abnormalities • Facial dysmorphism • Mitral valve abnormalities • Branch artery involvement • Timing of autopsy • External examination • Aortic dimensions • Aortic pathologies • Dissection characteristics • Aortic valve • Cardiac features • Congenital anomalies • Previous interventions • Extra-aortic pathologies Reproductive and Pregnancy Outcomes Hormonal Influences and Reproductive Health • Maternal age • Diagnosis • Pregnancy information • Delivery information • Pregnancy outcomes • Peripartum imaging • Aortic complications • Extra-aortic complications • Neonatal complications • Hormonal contraception or replacement therapies • Menstrual cycles • Intrauterine devices • Gynecologic conditions Repository Descriptions from the MIABIS Framework Aortic Interventions • Contact information • Samples, cases, and tiers • Data availability • Disease conditions • Inclusion criteria • Dataset types • Collection design • Use and access conditions • Sample types • Storage conditions • Sample collection settings • Key publications • Timing • Procedure types • Acuity • Indications • Max diameter • Medical history • Anatomic sites • Procedural complications • Procedural mortality • TEVAR considerations • Access sites • Methods of perfusion • Methods of brain protection Social Determinants of Health Follow-up Data • Demographic characteristics (sex, gender, age) • Nonprescription drug use • Marital status • Education level • Socioeconomic status • Healthcare access • Aortic pathologies • Timing • Method • Success of attempt • Blood pressure • Aortic interventions • Aorta-related death • Reproductive outcomes • Mental health and QoL • Social determinants of health • Med & Enviro Exposures Note that noncore (italicized) data elements in Table 1 , Table 2 , Table 3 , Table 4 , Table 5 , Table 6 , Table 7 , Table 8 , Table 9 , Table 10 , Table 11 , Table 12 , Table 13 , Table 14 , Table 15 , Table 16 , Table 17 , Table 18 , Table 19 were not included in this table. Tier 1 elements in red; tier 2 elements in green; tier 3 elements in blue; optional elements in orange. HbA1c = hemoglobin A1c; HTAD = heritable thoracic aortic disease; INR = international normalized ratio; MIABIS = Minimum Information About Biobank Data Sharing; QoL = quality of control; TAD = thoracic aortic disease; TEVAR = thoracic endovascular aortic repair. Core Data Elements for Evaluation of Thoracic Aortic Disease Annulus Sinuses of Valsalva Sino-tubular junction Ascending Arch Aortic isthmus Descending Timing of study Imaging modality Location Perpendicular landmark Edges Sinus measurements Height Weight Timing of diagnosis Dilation Aneurysm Dissection Penetrating ulcer Intramural hematoma Rupture Coarctation Patent ductus arteriosus Aortic valve morphology Timing of measurement Clinic blood pressures (>2) Self-measured blood pressures (>2) Heart rate Ambulatory blood pressure Nocturnal dipping Anxiety Depression Post-traumatic stress Health-related QoL Chronic stress Subjective social status Adverse childhood Perceived discrimination Social isolation Medication name Medication dose Medication frequency Duration of use Low-density lipoprotein HbA1c INR Age at initial presentation Reason: relative Reason: aortic dissection Reason: incidental Reason: examination Reason: symptoms Genetic diagnosis of individual Genetic test result of individual Genetic test results of relatives DNA variant and reference sequence Protein variant and reference sequence Genetic ancestry Pectus anomaly Skeletal abnormalities Long limbs Foot deformities Premature osteoarthritis Pneumothorax Joint hypermobility Dural ectasia Skin abnormalities Eye abnormalities Facial dysmorphism Mitral valve abnormalities Branch artery involvement Timing of autopsy External examination Aortic dimensions Aortic pathologies Dissection characteristics Aortic valve Cardiac features Congenital anomalies Previous interventions Extra-aortic pathologies Maternal age Diagnosis Pregnancy information Delivery information Pregnancy outcomes Peripartum imaging Aortic complications Extra-aortic complications Neonatal complications Hormonal contraception or replacement therapies Menstrual cycles Intrauterine devices Gynecologic conditions Contact information Samples, cases, and tiers Data availability Disease conditions Inclusion criteria Dataset types Collection design Use and access conditions Sample types Storage conditions Sample collection settings Key publications Timing Procedure types Acuity Indications Max diameter Medical history Anatomic sites Procedural complications Procedural mortality TEVAR considerations Access sites Methods of perfusion Methods of brain protection Demographic characteristics (sex, gender, age) Nonprescription drug use Marital status Education level Socioeconomic status Healthcare access Aortic pathologies Timing Method Success of attempt Blood pressure Aortic interventions Aorta-related death Reproductive outcomes Mental health and QoL Social determinants of health Med & Enviro Exposures Note that noncore (italicized) data elements in Table 1 , Table 2 , Table 3 , Table 4 , Table 5 , Table 6 , Table 7 , Table 8 , Table 9 , Table 10 , Table 11 , Table 12 , Table 13 , Table 14 , Table 15 , Table 16 , Table 17 , Table 18 , Table 19 were not included in this table. Tier 1 elements in red; tier 2 elements in green; tier 3 elements in blue; optional elements in orange. HbA1c = hemoglobin A1c; HTAD = heritable thoracic aortic disease; INR = international normalized ratio; MIABIS = Minimum Information About Biobank Data Sharing; QoL = quality of control; TAD = thoracic aortic disease; TEVAR = thoracic endovascular aortic repair.

Blood pressure is a major determinant of TAD outcomes, such as aortic dissection, aortic dilation rates, and reinterventions after aortic operations. Systolic blood pressure and pulse pressure are most strongly linked to adverse outcomes. Blood pressure readings fluctuate over time and are best assessed by calculating the mean of 2 or 3 consecutive measurements and by documenting circadian variation of blood pressures. 20 Therefore, the systolic pressure, diastolic pressure, and heart rate should be extracted from at least 3 clinic visits or procedure reports for each research participant across the study period, along with the date and time of each measurement ( Table 6 ). We propose that at least one set of blood pressure readings should be collected for each year that the participant is in a research study and as close as possible to the time of meaningful events, such as surveillance images or procedures. If self-measured blood pressures or 24-hour ambulatory blood pressure monitoring (ABPM) reports are available, the mean systolic and diastolic pressures, along with some measure of blood pressure variability, such as the standard deviation or average real variability, should be recorded separately for the daytime and nighttime. 21 Nocturnal dipping as a percentage decrease of the mean arterial pressure is also usually available from ABPM data. Both hypertension and impaired or reversed nocturnal dipping are frequent in TAD cohorts and are independent predictors of cardiovascular outcomes. 22 To enhance phenotypic characterization and risk stratification, ABPM data should be routinely acquired in prospective TAD research cohorts and clinical trials. Table 6 Data Elements for Blood Pressure Measurements Element Definition Details Timing of blood pressure measurement Date and time of measurement a  Clinic blood pressure b Measured in clinic, office, or at the time of procedures • Abstracted from notes or procedure reports  Self-measured blood pressure b Measured by patient • Usually submitted as a diary Heart rate Beats per minute  Ambulatory blood pressure Ambulatory blood pressure monitoring (ABPM) • At least 27 readings in one 24-hour period • Day and night periods analyzed separately • Reported as mean and variability c  Nocturnal dipping Physiological drop in blood pressure during sleep • Only in ABPM data • Percentage of mean arterial pressure Italicized items are optional but strongly encouraged. Clinic blood pressures, self-measured blood pressures, and the mean value of one ambulatory blood pressure monitoring period count toward the minimum of at least 3 blood pressure readings per participant or at least 1 blood pressure reading for every year that the participant is in the study. ABPM = ambulatory blood pressure monitoring. a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. b Blood pressure should be reported after 3 consecutive measurements taken 1 minute apart. Drop the first reading and take the mean of the second and third readings. c Blood pressure variability can be calculated as the standard deviation, coefficient of variation, or average real variability. 21 Data Elements for Blood Pressure Measurements Abstracted from notes or procedure reports Usually submitted as a diary At least 27 readings in one 24-hour period Day and night periods analyzed separately Reported as mean and variability c Only in ABPM data Percentage of mean arterial pressure Italicized items are optional but strongly encouraged. Clinic blood pressures, self-measured blood pressures, and the mean value of one ambulatory blood pressure monitoring period count toward the minimum of at least 3 blood pressure readings per participant or at least 1 blood pressure reading for every year that the participant is in the study. ABPM = ambulatory blood pressure monitoring. Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. Blood pressure should be reported after 3 consecutive measurements taken 1 minute apart. Drop the first reading and take the mean of the second and third readings. Blood pressure variability can be calculated as the standard deviation, coefficient of variation, or average real variability. 21

Aortic interventions are either the focus or a major endpoint of many studies. To permit unbiased comparisons between studies, it is important to document the indication for a procedure, the acuity of presentation, the maximum aortic diameter prior to intervention, procedure type and extent, and periprocedural complications in a standardized format ( Table 17 ). We recommend using published standards to report technical details about aortic repairs. 13 , 76 , 77 When interventions include concomitant aortic valve repair or replacement, reporting standards for valve interventions should also be followed. 78 Table 17 Data Elements to Describe Aortic Interventions Element Attributes Open Repairs Endovascular Repairs Ascending/Arch Descending/Thoracoabdominal Timing of procedure Age at or date of intervention a Maximum diameter Maximum aortic diameter on imaging study prior to intervention Acuity of presentation Emergency, urgent, elective Indications for procedure Heritable risk, symptoms, aneurysm, dissection (chronic, subacute, acute), rupture, infection, malperfusion, aortic valve regurgitation Medical conditions b Hypertension, Hyperlipidemia, Diabetes, Smoking, Chronic pulmonary disease, Chronic renal disease, MI, Heart failure, Stroke, Previous interventions Anatomic sites (Ishimaru Zones) Zones 0-4 Zones 5-9 Zones 0-9 Procedure types • Sinuses (CVG, David, Yacoub) • Ascending • Arch (hemi, total, ET) • DTA replacement • TAAA replacement (Crawford extents) • Ascending • Arch • TEVAR • F-BEVAR TEVAR considerations • Does not apply • Does not apply • Staging • Landing zone native • Extent of coverage • Proximal and distal aorta and device diameters Arterial cannulation or access sites • Direct aortic • Femoral • Axillary/innominate • Femoral • Axillary • Direct aortic • Femoral • Iliac • Carotid • Axillary/brachial Venous cannulation or access sites • Right atrium • SVC/IVC • Femoral • Left atrium • Pulmonary vein • Femoral • Venous access if Zone 0 Methods of perfusion • Full CPB • Hypothermia (mild, moderate deep) • LA-FA • ECMO • Full CPB • Does not apply Methods of brain protection • DHCA • Antegrade • Retrograde • DHCA • CSF drainage • CSF drainage Procedural complications • Neurologic complications (stroke, paraplegia), major bleeding, MI, congestive heart failure, respiratory failure, renal failure, graft or device infection • Re-exploration • Pseudoaneurysm • Valve dysfunction • Visceral ischemia • Limb ischemia • Re-exploration • Pseudoaneurysm • Endoleak • Retrograde dissection • SINE • Access site complications • Device migration Procedural mortality Death within 30 d or any time during initial hospitalization, including transfers We recognize that procedural data may be collected retrospectively and that some elements may not be available to researchers. Italicized elements: optional for registries that are not surgically centered; heritable risk: decision for preventative procedure primarily guided by genetic information. CPB = cardiopulmonary bypass; CSF = cerebrospinal fluid; CVG = composite valve graft with a mechanical or bioprosthetic prosthesis; DHCA = deep hypothermic circulatory arrest; DTA = descending thoracic aorta; ECMO = extracorporeal membrane oxygenation; ET = elephant trunk; F-BEVAR = fenestrated and/or branched endovascular aortic repair; IVC = inferior vena cava; LA-FA = left atrium to femoral artery or other arterial site; MI = myocardial infarction; SVC = superior vena cava; TEVAR = thoracic endovascular aortic repair; re-exploration: such as for bleeding, dehiscence, infection, or effusion; SINE = stent-induced new entry tear; TAAA = thoracoabdominal aortic aneurysm. a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. b See Table 9 , Table 10 . Data Elements to Describe Aortic Interventions Sinuses (CVG, David, Yacoub) Ascending Arch (hemi, total, ET) DTA replacement TAAA replacement (Crawford extents) Ascending Arch TEVAR F-BEVAR Does not apply Does not apply Staging Landing zone native Extent of coverage Proximal and distal aorta and device diameters Direct aortic Femoral Axillary/innominate Femoral Axillary Direct aortic Femoral Iliac Carotid Axillary/brachial Right atrium SVC/IVC Femoral Left atrium Pulmonary vein Femoral Venous access if Zone 0 Full CPB Hypothermia (mild, moderate deep) LA-FA ECMO Full CPB Does not apply DHCA Antegrade Retrograde DHCA CSF drainage CSF drainage Neurologic complications (stroke, paraplegia), major bleeding, MI, congestive heart failure, respiratory failure, renal failure, graft or device infection Re-exploration Pseudoaneurysm Valve dysfunction Visceral ischemia Limb ischemia Re-exploration Pseudoaneurysm Endoleak Retrograde dissection SINE Access site complications Device migration We recognize that procedural data may be collected retrospectively and that some elements may not be available to researchers. Italicized elements: optional for registries that are not surgically centered; heritable risk: decision for preventative procedure primarily guided by genetic information. CPB = cardiopulmonary bypass; CSF = cerebrospinal fluid; CVG = composite valve graft with a mechanical or bioprosthetic prosthesis; DHCA = deep hypothermic circulatory arrest; DTA = descending thoracic aorta; ECMO = extracorporeal membrane oxygenation; ET = elephant trunk; F-BEVAR = fenestrated and/or branched endovascular aortic repair; IVC = inferior vena cava; LA-FA = left atrium to femoral artery or other arterial site; MI = myocardial infarction; SVC = superior vena cava; TEVAR = thoracic endovascular aortic repair; re-exploration: such as for bleeding, dehiscence, infection, or effusion; SINE = stent-induced new entry tear; TAAA = thoracoabdominal aortic aneurysm. Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. See Table 9 , Table 10 . Ishimaru Zone classifications should be used to describe the distal extent of aortic arch repair. 11 , 12 The distal extent of “hemiarch” resections on the greater curvature of the arch is uniformly at the origin of the innominate artery in Zone 0. The distal extent of “hemiarch” resections on the lesser curvature may be highly variable and ranges from zone 0 to zone 3. Graft replacement of all native aortic sinus tissue with preservation and resuspension of the aortic valve inside the graft is known as a “valve-sparing aortic root replacement,” which has several technical variations. The most common technique is the “reimplantation” or “David procedure,” in which the aortic valve is resuspended fully inside a graft that is seated externally at the level of the virtual basal ring. A similar procedure, known as “aortic root remodeling” or “Yacoub procedure,” involves replacement of all sinus tissue using a scalloped graft, such that no part of the graft extends below the level of the aortic annulus with the possible addition of an external ring annuloplasty. 79 If endovascular approaches are used, many of the considerations for arterial access and complications are similar, but the risk of iatrogenic dissection may be increased, depending on the aortic segment being treated and the genetic diagnosis. Core data elements about endovascular interventions should ideally include: 1) concurrent or staged timing with respect to open repairs; 2) whether stent landing zones involve native aorta or prosthesis; 3) extent of aortic coverage (hemiarch, total arch, Crawford thoracoabdominal extent I-IV); and 4) aortic and device diameters at the proximal and distal landing zones. Elective or emergent indications for endovascular repair should also be documented ( Table 17 ).

Health-related quality of life (HRQoL) describes physical, social, and psychological aspects of well-being that influence health status and functioning. 23 Data about HRQoL are almost completely absent from current TAD registries, but there is evidence that TAD has negative impacts on HRQoL. 24 Depression and/or anxiety affect up to one-third of dissection survivors. Post-traumatic stress is also common in this population. 25 We recommend 4 widely validated screening instruments for anxiety (Generalized Anxiety Disorder 7-item questionnaire), depression (Patient Health Questionnaire-9), post-traumatic stress disorder (Post Traumatic Stress Disorder 5-item questionnaire), and HRQoL (the Medical Outcomes Study 36-Item Short-Form Health Survey for adults or the Pediatric Quality of Life Inventory for children and adolescents) that can be collected rapidly in most clinical settings, but other instruments are available ( Table 7 , Supplemental Table 9 ). 24 , 25 , 26 , 27 , 28 Note that none of these instruments measure food insecurity, and only one instrument, the World Health Organization Quality of Life, measures perceived physical safety, a major component of well-being. In a GenTAC study of individuals with Marfan syndrome, 36-Item Short-Form Health Survey scores (n = 389, mean age 41 years; 51% men) were reduced compared to general population norms. 24 Table 7 Data Elements to Describe Mental Health and Quality of Life Element Instrument(s) for Assessment References Anxiety GAD-7 Suppl Refs 85,86 Depression PHQ-2, PHQ-9 Suppl Refs 87,88 Post-traumatic stress PTSD-5, PCL Suppl Refs 89,90 Health-related quality of life SF-36 or equivalent a Suppl Refs 91,92 Chronic psychological stress Perceived Stress Scale (PSS-4) Suppl Ref 93 Subjective social status MacArthur ladder Suppl Ref 94 Adverse childhood experiences Whitehall II ACE assessment Suppl Ref 95 Perceived discrimination Perceived Ethnic Discrimination Questionnaire (PED-Q) Suppl Ref 96 Loneliness or social isolation Social isolation index score Suppl Ref 97 Italicized: optional data elements. PedsQL is the most widely used pediatric equivalent. ACE = adverse childhood experiences; GAD-7 = Generalized Anxiety Disorder 7-item questionnaire; PCL = PTSD Checklist; PedsQL = Pediatric Quality of Life Inventory; PHQ-2 = Patient Health Questionnaire-9; PHQ-9 = Patient Health Questionnaire-9; PTSD-5 = Post Traumatic Stress Disorder 5-item questionnaire; SF-36 = Short Form Health Survey 36-item questionnaire. a See Supplemental Table 9 . Data Elements to Describe Mental Health and Quality of Life Italicized: optional data elements. PedsQL is the most widely used pediatric equivalent. ACE = adverse childhood experiences; GAD-7 = Generalized Anxiety Disorder 7-item questionnaire; PCL = PTSD Checklist; PedsQL = Pediatric Quality of Life Inventory; PHQ-2 = Patient Health Questionnaire-9; PHQ-9 = Patient Health Questionnaire-9; PTSD-5 = Post Traumatic Stress Disorder 5-item questionnaire; SF-36 = Short Form Health Survey 36-item questionnaire. See Supplemental Table 9 . While it may not be possible to extract HRQoL data from retrospective or historical data, all prospective TAD registries should collect data on mental health and HRQoL at enrollment and ideally at each follow-up contact using one or more of these validated questionnaires or equivalent instruments. Due to the prevalence of mental health concerns in the TAD population, it may be reasonable to develop specific mental health assessment tools for TAD patients.

Social determinants of health (SDH) are nonmedical factors that affect access to health care, adherence to therapies, and supportive resources. 29 SDH are strongly associated with measured cardiovascular risk factors, vascular inflammation, and incident cardiovascular disease. Therefore, disparities in SDH may be important confounders of aortic health outcomes, and we strongly recommend that all prospective TAD registries collect data on SDH at enrollment and at each follow-up contact ( Table 8 ). Table 8 Data Elements to Describe Social Determinants of Health Elements Attributes Options Demographics Current age or date of birth a Sex at birth Male, female, intersex Gender Male, female, nonbinary, transgender Marital status Married, single, divorced, widowed Education level International Standard Classification of Education b Nonprescription drugs Cigars or cigarettes Current and pack-years, former and pack-years, never E-cigarettes or vapes Current, former, never Alcohol Current and drinks per week, former and drinks per week, never Cocaine Current, former, never Opioids or narcotics Current, former, never Amphetamines or stimulants Current, former, never Socioeconomic status Public assistance Food supplement, unemployment benefits, welfare or equivalent Employment status Permanent worker, temporary worker, unemployed Healthcare access c Government insurance or universal health care Yes, no Personal or private health insurance Yes, no Italicized elements: optional but strongly recommended if feasible. a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. b Defined as by Dienhart et al. Suppl Ref 98 c Perceived healthcare access can also be assessed using the Healthcare Access and Quality Index Suppl Ref 99 or the Perceived Access to Healthcare Questionnaire. Suppl Ref 100 Data Elements to Describe Social Determinants of Health Italicized elements: optional but strongly recommended if feasible. Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. Defined as by Dienhart et al. Suppl Ref 98 Perceived healthcare access can also be assessed using the Healthcare Access and Quality Index Suppl Ref 99 or the Perceived Access to Healthcare Questionnaire. Suppl Ref 100

More than half of type A aortic dissections lead to sudden death. 55 Yet data related to autopsies or death investigations are not routinely collected in TAD registries, and there are no standards for documentation of TAD in postmortem examinations. For sudden deaths that are attributed to aortic dissection, macroscopic and histological evaluation of the entire aorta is essential, particularly in subjects with HTAD. 56 , 57 Data about demographic characteristics and cardiovascular history, including previous aortic interventions, should be documented. Specific pathological data about the location and extent of aortic dissections, the maximum aortic diameter, and congenital heart or vascular malformations should also be reported ( Table 13 ). Postmortem CT or MRI imaging should be considered as a potential alternative when a conventional autopsy is not available. Table 13 Data Elements for Autopsy Element Description Timing of autopsy Age at death or date of death a External examination b Physical features Aortic dimensions c Sinuses of Valsalva Ascending aorta Maximum external diameter and location Maximum internal diameter and location Aortic pathologies d Dissection Intramural hematoma Penetrating ulcer Rupture Cystic medial degeneration e Dissection characteristics d Number of flaps, acute or chronic Entry and exit tear location(s) Aortic valve morphology Bicuspid aortic valve and type of fusion Calcification Stenosis Cardiac features Ventricular wall thickness Implantable cardiac devices Congenital anomalies Septal defects Mitral valve prolapse Aortic coarctation Sub or supravalvular stenosis Arch anomalies Previous interventions Aortic stents Aortic grafts Valve prostheses Extra-aortic pathologies Cardiac tamponade Thoracic hemorrhage Arterial aneurysms Pneumothorax a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. b See the Genetic data section. c If data collected from postmortem images, see Thoracic aortic measurements section for reporting specifications. d See the Thoracic Aortic Pathologies section. e On histological analysis. Data Elements for Autopsy Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. See the Genetic data section. If data collected from postmortem images, see Thoracic aortic measurements section for reporting specifications. See the Thoracic Aortic Pathologies section. On histological analysis. As recommended in current guidelines, genetic tests of blood or tissue samples from autopsies should be reported for younger individuals (<60 years) with aortic dissections or adults with thoracic aortic aneurysms and clinical features suggestive of HTAD. 58 , 59 Positive genetic tests should trigger gene-based management and cascade testing of at-risk relatives. 2 When genetic tests are negative or identify variants of uncertain significance, first-degree relatives should be screened by aortic imaging. Ideally, familial screening results (when available) should be included with the genetic data of research participants (see Genetic data section).

Currently, up to one-third of individuals with TAD have a PV or likely PV in a single gene that is responsible for their condition. 45 , 46 , 47 PVs of some genes ( MYLK , PRKG1 , SMAD3 , TGFB2 , TGFBR1 , TGFBR2 , COL3A1 ) are associated with early-onset dissections at relatively small aortic diameters (<5.0 cm). 48 , 49 , 50 , 51 Identification of a heritable component has important implications for familial screening and the appropriate timing of surgical repair. Researchers should document if clinical genetic testing and/or familial segregation studies were performed and if a PV or Variant of Uncertain Significance was identified. To facilitate data sharing, uniform information about genetic variants should be documented using approved American College of Medical Genetics and Genomics nomenclature ( Table 11 ). 52 Due to historical changes in reference sequences, it is essential to document the DNA and protein annotations of a variant with the appropriate genome and transcript information. Notably, information about genetic variants is readily accessible from commercial laboratory test reports, even by investigators who have no formal training in genetics. Because the expected frequency of a variant may differ according to ancestry and geographic region, documentation of ethnic ancestry is important for contextual analysis of genetic data. Table 11 Data Elements for Uniform Genetic Variant Information Element Description Genetic diagnosis of individual Clinical impression, even if no test result Genetic test result of individual Yes, no, age when tested, type of test, gene, VUS/LP/P Genetic test results of relatives Yes, no, relatives tested, type of test, gene, VUS/LP/P DNA variant and reference sequence Transcript isoform and nucleotide change Protein variant and reference sequence Protein isoform and amino acid change Genetic ancestry Race and ethnicity a The current minimum categories are: American Indian or Alaska Native, Asian, Black or African American, Hispanic or Latino, Middle Eastern or North African, Native Hawaiian or Pacific Islander, and White. LP = likely pathogenic; P = pathogenic; VUS = variant of uncertain significance. a Defined according to current minimum categories for data on race and ethnicity in federal statistics ( https://spd15revision.gov/content/spd15revision/en/2024-spd15/categories-definitions.html ). Data Elements for Uniform Genetic Variant Information The current minimum categories are: American Indian or Alaska Native, Asian, Black or African American, Hispanic or Latino, Middle Eastern or North African, Native Hawaiian or Pacific Islander, and White. LP = likely pathogenic; P = pathogenic; VUS = variant of uncertain significance. Defined according to current minimum categories for data on race and ethnicity in federal statistics ( https://spd15revision.gov/content/spd15revision/en/2024-spd15/categories-definitions.html ). Some extra-aortic clinical features are relatively specific for heritable TAD (HTAD) ( Table 12 ). 53 These features, especially if prominent or severe, can potentially identify individuals who are at risk of earlier onset of TAD with a more rapid clinical course, and these specific features should be captured in aortic registries. 54 Table 12 Data Elements for Extra-aortic Features Associated With HTAD Element Description Important Details Pectus anomaly Excavatum, carinatum Chest asymmetry Skeletal abnormalities Scoliosis, kyphosis, spondylolisthesis Surgical correction, fractures Disproportionately long limbs and digits Arachnodactyly Arm span to height ratio Upper to lower segment ratio Foot deformities Club foot, flat foot Unilateral or bilateral, surgical correction Premature osteoarthritis Early onset (<40 y) Characteristic of SMAD3 PV Pneumothorax Spontaneous Recurrent or bilateral Joint hypermobility Wrist sign, thumb sign, nontraumatic joint dislocations Recurrent or multiple joints Dural ectasia On CT or MR images Tarlov cysts Skin abnormalities Thin translucent skin, easy bruising, stretch marks, atrophic scars History of delayed wound healing Translucent velvety skin specific for VEDS Eye and vision abnormalities Lens dislocation, severe myopia Lens dislocation specific for FBN1 PV Facial dysmorphism Hypertelorism, retrognathia, malar hypoplasia, dolichocephaly, cleft palate, bifid uvula Bifid uvula specific for LDS Mitral valve abnormalities Mitral valve prolapse, mitral annular disjunction Mitral annular disjunction characteristic of LDS Involvement of branch arteries Specify location(s) Cervical and iliac artery involvement characteristic of LDS and VEDS Features were included if clearly visible on examination or likely to be documented on routine imaging reports. Features should be scored as present even if repaired. Mitral annular disjunction: defined as by Asokan et al. Suppl Ref 101 CT = computed tomography; HTAD = heritable thoracic aortic disease; LDS = Loeys-Dietz syndrome; MR = magnetic resonance; PV = pathogenic variants; VEDS = Vascular Ehlers-Danlos syndrome. Data Elements for Extra-aortic Features Associated With HTAD Features were included if clearly visible on examination or likely to be documented on routine imaging reports. Features should be scored as present even if repaired. Mitral annular disjunction: defined as by Asokan et al. Suppl Ref 101 CT = computed tomography; HTAD = heritable thoracic aortic disease; LDS = Loeys-Dietz syndrome; MR = magnetic resonance; PV = pathogenic variants; VEDS = Vascular Ehlers-Danlos syndrome.

Patients may be referred for evaluation of suspected TAD due to a variety of circumstances and findings: a family history of sudden cardiac death, especially in a young (<60 years) person; being the relative of a patient with recognized aortic pathology; aortic dilation incidentally discovered during an evaluation for another reason, especially in a young person who does not have hypertension; aortic dissection or other arterial dissection; unexplained hypertension in a young, otherwise healthy person; or physical features, such as an ectopic lens, a chest deformity (excavatum, carinatum, scoliosis), spontaneous pneumothorax, or atrophic scars (see Genetic data section). Less common reasons for ascertainment include severe bruising in children or an incidental finding of a PV on exome sequencing for an unrelated etiology. The reason for referral defines many characteristics of the population being evaluated, which in turn can determine the severity of disease at presentation. For example, relatives who are identified due to cascade screening are usually less severely affected than probands, while patients who are identified due to aortic dissections, particularly at a young age, may have early-onset syndromic forms of TAD. Therefore, it is essential to document the age at initial presentation and the principal reason for ascertainment ( Table 10 ). Table 10 Data Elements to Describe Reasons for Evaluation of Suspected TAD Element Description Timing of initial presentation a Age or date; first contact, not necessarily diagnosis Reason: relative or genetic variant Pathogenic variant, positive imaging, history of aortic disease, or exam finding Reason: aortic dissection May only be diagnosed at autopsy Reason: incidental Imaging for an unrelated reason identifies TAD Reason: examination Clinical features that raise clinical suspicion for HTAD Reason: symptoms Palpitations, pain, congestive heart failure HTAD = heritable thoracic aortic disease; TAD = thoracic aortic disease. a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. Data Elements to Describe Reasons for Evaluation of Suspected TAD HTAD = heritable thoracic aortic disease; TAD = thoracic aortic disease. Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information.

Documentation of aortic outcomes is a central aspect of most TAD studies. Priority core data elements that should be updated at each follow-up contact include vital status, aortic interventions, aortic pathologies, and cardiovascular medications ( Table 18 ). The methods that were used to investigate the status of study participants should also be recorded. Table 18 Minimum TAD Data Elements To Be Updated at Each Study Contact Element Table Timing of follow-up a - Method of follow-up: in person, call or message, health or government record, family or friend - Success of follow-up: yes and living, yes and dead, no - Aorta-related death: yes and date or age, no - Aortic pathologies 5 Blood pressure measurements 6 Mental health and quality of life 7 Social determinants of health 8 Medication and environmental exposures 9 Reproductive outcomes 14 Aortic interventions 17 a Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. Aorta-related death: death that is clearly related to an aortic pathology or from further intervention performed for a new aortic event, or sudden death in the absence of confirmation or an alternate cause. Suppl Ref 103 Minimum TAD Data Elements To Be Updated at Each Study Contact Specific dates should only be collected if authorized and should be rounded to the nearest year or exported from the registry as ages to protect identifiable health information. Aorta-related death: death that is clearly related to an aortic pathology or from further intervention performed for a new aortic event, or sudden death in the absence of confirmation or an alternate cause. Suppl Ref 103

Beta blockers and angiotensin receptor blockers are mainstays of medical therapy for TAD. While a beneficial “class effect” of these medications on aortic dilation and dissection has been established, it is unclear if the choice of specific medications in each class affects aortic outcomes, and it is not certain that all medication effects are dose-dependent. 30 Future studies should focus on comparisons of medications and doses for cumulative evidence of treatment effects over time. Some medications are reliable indicators of conditions that affect cardiovascular health, such as hypertension, hyperlipidemia, or diabetes mellitus. Medication data can affirm and supplement the existence of a health condition by providing a quantifiable marker of health status. Therefore, we recommend that the specific medication, dose, frequency, start date, and duration of therapy, as well as some measure of disease status or treatment efficacy (when available), should be recorded for research purposes ( Table 9 ). These measures should be updated at each follow-up contact to determine changes in medication use. Table 9 Data Elements for Medication and Environmental Exposures Elements Description Medication name a Any cardiovascular medication Medication dose Milligrams per dose Medication frequency Number per day Duration of medication use If > 1 y, current age—age at start   Low-density lipoprotein (LDL) Proxy for hyperlipidemia   Glycated hemoglobin (A1c) or blood glucose b Proxy for diabetes   International Normalized Ratio (INR) c Efficacy of anticoagulation   Postal codes d Beginning 10 y prior to enrollment   US county subdivisions, EU NUTS 2-3 or LAU Searchable in US county or EU data   Census tracts or block groups e Searchable in US census data Italicized elements: optional but strongly recommended if feasible. A searchable database of US census data is available at https://censusreporter.org . A searchable database of US county data is available at public.opendatasoft.com/explore/dataset/public-catalog/table. Searchable online EU NUTS data is available at https://data.europa.eu/data . Non-US/EU exposure data are available from other national or regional repositories. Note that postal codes and other geographic location data are considered to be protected health information and usually require explicit participant consent to be stored or shared. EU = European Union; LAU = Local Administrative Units; NUTS = Nomenclature of Territorial Units for Statistics; US = United States. a Use of all cardiovascular medications should be documented at each follow-up contact. We recommend that medication use and/or a measure of disease status or treatment efficacy (eg, LDL for hyperlipidemia or blood pressure for hypertension) should be used to confirm the diagnosis of a health condition when those measures are available. b Mean of at least 3 blood glucose measurements. c Document the closest value to each follow-up contact. d Record the last 3 residence locations. e The census block group is the smallest area unit in United States census data. Data Elements for Medication and Environmental Exposures Italicized elements: optional but strongly recommended if feasible. A searchable database of US census data is available at https://censusreporter.org . A searchable database of US county data is available at public.opendatasoft.com/explore/dataset/public-catalog/table. Searchable online EU NUTS data is available at https://data.europa.eu/data . Non-US/EU exposure data are available from other national or regional repositories. Note that postal codes and other geographic location data are considered to be protected health information and usually require explicit participant consent to be stored or shared. EU = European Union; LAU = Local Administrative Units; NUTS = Nomenclature of Territorial Units for Statistics; US = United States. Use of all cardiovascular medications should be documented at each follow-up contact. We recommend that medication use and/or a measure of disease status or treatment efficacy (eg, LDL for hyperlipidemia or blood pressure for hypertension) should be used to confirm the diagnosis of a health condition when those measures are available. Mean of at least 3 blood glucose measurements. Document the closest value to each follow-up contact. Record the last 3 residence locations. The census block group is the smallest area unit in United States census data. Exposure to medications can be calculated as the total daily dose, the assumed average maintenance dose, or the weighted cumulative exposure, which incorporates factors such as dose intensity, adherence, or duration into a single metric ( Supplemental Table 10 ). Adjusting for the relative effectiveness of medications using dose equivalence tables may facilitate comparisons ( Supplemental Table 11 ). 31 Confirming patient adherence to medical therapies is essential to understand the relationship between dose and treatment outcomes. Patient adherence can be measured by self-report (Morisky Medication Adherence Scale or Brief Medication Questionnaire) or pharmacy refill records, using measures such as the medication possession ratio, which is the ratio of the total dose that was dispensed to the number of days in a time interval. 32 , 33 , 34 , 35 , 36 Measurement of drug levels other than the international normalized ratio is not routinely available and may be more relevant to early-phase clinical trials or animal studies. Subtherapeutic international normalized ratio levels, especially when longitudinal data are available, may be a useful proxy for medication nonadherence ( Table 9 ). 37 Similarly, fluctuations in low-density lipoprotein levels or the percentage of glycated hemoglobin (A1c) may indicate nonadherence to therapies. Heart rate data may be a useful proxy for the effectiveness of beta-blocker medications. Data on environmental exposures to air pollution, green spaces, and sociodemographic factors, such as crime or food deserts, are increasingly available at neighborhood-level resolution. 38 , 39 , 40 , 41 , 42 These exposures and other SDH are now recognized to be potent risk factors that modify cardiovascular health and mortality. It is possible that, similar to other cardiovascular conditions, environmental exposures may exacerbate and/or accelerate the clinical presentation and outcomes of TAD. 29 To link participant-level data to cumulative environmental exposures, it is essential to record the residential history of study participants, balancing participant privacy with the necessity to obtain accurate geographic location data. Neighborhood data, such as county subdivisions, census tracts, or census block groups corresponding to home addresses, can be retrieved from searchable online databases ( Table 9 ). When feasible, TAD registries should collect postal codes and/or data on localities where study participants resided beginning at least 10 years prior to study enrollment and updating this information at each subsequent study contact. In many countries, some local geographic location data are designated as private health information and cannot be shared as individual-level data without the informed consent of registry participants. However, coded environmental exposure data are not generally subject to these restrictions and can be readily derived from geographic information systems data using an automated commercial software program. 43 , 44 Therefore, it may be possible for researchers to receive geocoded data on environmental exposures from retrospective registries as appropriate for a specific research question. In our view, all prospective TAD registries should obtain informed consent for location data.

The Minimum Information About Biobank Data Sharing (MIABIS) project introduced standardized variables that researchers can use to query biorepositories for available samples and associated clinical data. MIABIS was created in 2012 and underwent 2 subsequent revisions to expand the repertoire of standardized terminology so that it now includes datasets as well as samples. 75 The units of record in MIABIS are individual samples with related information about sample donors, clinical phenotypes, and sample repositories. The repository-level descriptors define potential restrictions on sample availability for commercial or disease-specific uses that have been adopted by the National Institutes of Health and the European Union. Currently, only 2 of the aortopathy repositories include extensive information about biological samples (GenTAC, Vascular European Reference Network), but neither repository contains all core MIABIS descriptors. We propose that aortopathy repositories utilize the MIABIS framework and make these data freely available to researchers ( Table 16 ). Table 16 Data Elements for Repository Descriptions From the MIABIS Framework Element Description Contact information URL or individual contacts for repository Dataset types Data about sample donors or samples in the repository, ie, available to researchers Sample types Available biospecimens Storage conditions Liquid nitrogen, −80 °C, etc Disease conditions Disease names or categories of disease Sample collection settings The contexts in which the samples were collected (eg, clinical trial) Collection designs The overall design of the study (eg, disease-specific cohort) Use and access conditions Restrictions on use of samples or data for specific purposes, usually in consent documentation a Samples or cases and tiers Number of samples or cases and tier(s) b of recorded data Data availability Tier a of data (retrospective or prospective) potentially available on request Inclusion criteria Inclusion and exclusion criteria of studies that resulted in collection of the samples Key publications Publications that utilized samples or data from repository Data elements in this table were adapted from Eklund et al. Suppl Ref 102 MIABIS = Minimum Information About Biobank Data Sharing. a The MIABIS governance model was specifically created to enhance interoperability among registries sharing data and samples worldwide ( https://www.bbmri-eric.eu/howtomiabis/ ). b Data element tiers are defined as in Supplemental Tables 2 to 4 . Registries should list the tier that most closely matches currently available data. Data Elements for Repository Descriptions From the MIABIS Framework Data elements in this table were adapted from Eklund et al. Suppl Ref 102 MIABIS = Minimum Information About Biobank Data Sharing. The MIABIS governance model was specifically created to enhance interoperability among registries sharing data and samples worldwide ( https://www.bbmri-eric.eu/howtomiabis/ ). Data element tiers are defined as in Supplemental Tables 2 to 4 . Registries should list the tier that most closely matches currently available data.

TAD is a rare disease with potentially devastating outcomes. Advances in diagnosis and management can be most effectively achieved through collaborative research. We surveyed 10 contemporary TAD registries and identified significant gaps in the amount and types of data that are needed for accurate, verifiable, and reproducible studies. In several categories, relatively little data (eg, Reproductive Health) or no data (eg, Autopsy) is being collected systematically on TAD cohorts ( Table 19 ). Table 19 Representation of Consensus Thoracic Aortic Disease Data Elements in Contemporary TAD Research Registries CLARITY = Collaborative for Longitudinal Aortic Research in the Young; GenTAC = National Registry of Genetically Triggered Aneurysms and Other Cardiovascular Conditions; IRAD = International Registry of Aortic Dissection; MAC = Montalcino Aortic Consortium; STS = Society of Thoracic Surgeons Adult Cardiac Surgery Database; VASCERN = European Reference Network for Rare Multisystemic Vascular Diseases; ROPAC = Registry of Pregnancy and Cardiac Disease; GEN-VEDSS = Vascular Ehlers-Danlos Syndrome Collaborative Natural History Study; SVS VQI = Society for Vascular Surgery Vascular Quality Initiative; HTAD = heritable thoracic aortic disease; SBP = systolic blood pressure; DBP = diastolic blood pressure; ABPM = ambulatory blood pressure monitoring; SMBP = self-measured blood pressure; MIABIS = Minimum Information About Biobank Data Sharing. Clear Circles: 0 or 1 core Element are Represented in each Category; Black circles: All data Elements in Category are Represented; Hashed Circles: 2 or More Elements in a Category but Does NOT Have all the Elements. Representation of Consensus Thoracic Aortic Disease Data Elements in Contemporary TAD Research Registries CLARITY = Collaborative for Longitudinal Aortic Research in the Young; GenTAC = National Registry of Genetically Triggered Aneurysms and Other Cardiovascular Conditions; IRAD = International Registry of Aortic Dissection; MAC = Montalcino Aortic Consortium; STS = Society of Thoracic Surgeons Adult Cardiac Surgery Database; VASCERN = European Reference Network for Rare Multisystemic Vascular Diseases; ROPAC = Registry of Pregnancy and Cardiac Disease; GEN-VEDSS = Vascular Ehlers-Danlos Syndrome Collaborative Natural History Study; SVS VQI = Society for Vascular Surgery Vascular Quality Initiative; HTAD = heritable thoracic aortic disease; SBP = systolic blood pressure; DBP = diastolic blood pressure; ABPM = ambulatory blood pressure monitoring; SMBP = self-measured blood pressure; MIABIS = Minimum Information About Biobank Data Sharing. Clear Circles: 0 or 1 core Element are Represented in each Category; Black circles: All data Elements in Category are Represented; Hashed Circles: 2 or More Elements in a Category but Does NOT Have all the Elements. The focus of this project is to provide core data elements that can be assessed directly and summarized efficiently in research records to close these gaps while developing standards to harmonize data across registries and clinical trials. The complete set of 125 core data elements recommended by this expert panel is intended to serve as a roadmap for future research combining precision registry data with genetic and/or computational data to uncover new TAD phenotypes and identify new risk factors for TAD ( Table 2 , Supplemental Table 1 ). To promote effective collaborative studies, we suggest that all TAD registries and clinical trials collect and report these core data elements and harmonize their existing datasets to align with the core element definitions. Intersocietal collaboration with other medical specialists such as obstetricians, radiologists, and medical examiners to promote these standards is ongoing and will be essential for more uniform collection and wider availability of these data. 80 We acknowledge that it may not be feasible for many centers to extract all core data elements due to limitations in time, personnel, and resources. Therefore, we defined graduated tiers for data collection, beginning with a minimum dataset that contains <30 core aortic elements. Registries should indicate the tier(s) that most closely match their currently available data and the scope of data that could be obtained on request, along with other registry descriptors ( Table 16 ). We anticipate that these features will lower barriers to participation in collaborative research while providing transparent information to potential collaborators about available data. Future iterations of this project will need to consider data storage and transfer requirements for genetic analysis or computational modeling of the aorta, which is rapidly entering mainstream clinical practice for prognostication and interventional planning. Software and hardware specifications to extract these data are evolving. Standardization of data-acquisition protocols and definition of minimum requirements for computational modeling will be essential for future collaborative studies.

In preparation for this project, we surveyed 10 contemporary TAD registries to understand the scope of data that is currently available to TAD researchers. These registries reflect a broad range of research emphasis areas and demographic characteristics ( Table 1 , Central Illustration ). Table 1 Contemporary TAD Registries Name Population Images or Samples Site or Contact Year Started and Enrollment (N) CLARITY: Collaborative for Longitudinal Aortic Research In The Young Children and young adults with any aortopathy Images clarityregistry.com 2021 N = 1,700 Cornell Aortic Aneurysm Registry Adult aortopathy patients evaluated at Weill Cornell Medical Center Images Weill Cornell Medicine 2008 N = 700 GenTAC: National Registry of Genetically Triggered Aneurysms and Other Cardiovascular Conditions Children and adults with familial TAD, HTAD with known PV, and other TAD diagnosis with onset before age 50 Images and samples biolincc.org 2006 N = 3,600 IRAD: International Registry of Aortic Dissection Children and adults with acute aortic dissections Images iradonline.org 1996 N = 11,400 MAC: Montalcino Aortic Consortium Children and adults with HTAD due to known PV and their affected or unaffected relatives None montalcinoaorticconsortium.org 2013 N = 1,400 STS: Society of Thoracic Surgeons Adult Cardiac Surgery Database Adults undergoing cardiac and/or aortic surgeries Images sts.org 1989 N = 8.3 million procedures VASCERN: European Reference Network for Rare Multisystemic Vascular Diseases Children and adults with HTAD None vascern.eu/group/registry/sub-registries/heritable-thoracic-aortic-diseases-registry/ 2022 N = 3,700 ROPAC III: Registry of Pregnancy and Cardiac Disease Pregnant adults with prosthetic valves, aortic pathology, or genetic conditions known to be associated with aortic pathologies None escardio.org/Research/registries 2018 N = 1,100 GEN-VEDSS: Genetic Aortopathy and VEDS Collaborative Natural History Study Children and adults with genetically confirmed VEDS and VEDS-like conditions None [email protected] 2020 N = 186 SVS VQI: Society for Vascular Surgery Vascular Quality Initiative (TEVAR and complex EVAR) Adults undergoing endovascular aortic repair procedures in USA, Canada, and Singapore None [email protected] 2011 N = 40,000 procedures HTAD = heritable thoracic aortic disease; PV = pathogenic variants; TAD = thoracic aortic disease; TEVAR = thoracic endovascular aortic repair; VEDS = Vascular Ehlers-Danlos syndrome. Central Illustration Thoracic Aortic Disease Registry List Existing thoracic aortic disease registries were queried to identify overlaps with core data elements in disease categories. IRAD = International Registry of Aortic Dissection; MAC = Montalcino Aortic Consortium; QoL = quality of life; MIABIS = Minimum Information About Biobank Data Sharing; GEN-VEDSS = Vascular Ehlers-Danlos Syndrome Collaborative Natural History Study; ROPAC = Registry of Pregnancy and Cardiac Disease; STS = Society of Thoracic Surgeons Adult Cardiac Surgery Database; TAD = thoracic aortic disease; VASCERN = European Reference Network for Rare Multisystemic Vascular Diseases. Contemporary TAD Registries HTAD = heritable thoracic aortic disease; PV = pathogenic variants; TAD = thoracic aortic disease; TEVAR = thoracic endovascular aortic repair; VEDS = Vascular Ehlers-Danlos syndrome. Thoracic Aortic Disease Registry List Existing thoracic aortic disease registries were queried to identify overlaps with core data elements in disease categories. IRAD = International Registry of Aortic Dissection; MAC = Montalcino Aortic Consortium; QoL = quality of life; MIABIS = Minimum Information About Biobank Data Sharing; GEN-VEDSS = Vascular Ehlers-Danlos Syndrome Collaborative Natural History Study; ROPAC = Registry of Pregnancy and Cardiac Disease; STS = Society of Thoracic Surgeons Adult Cardiac Surgery Database; TAD = thoracic aortic disease; VASCERN = European Reference Network for Rare Multisystemic Vascular Diseases.

While pregnancy is a known risk factor for aortic dissection in the general population, individuals with TAD are at a much-heightened risk of aortic dissection, particularly during the third trimester and postpartum period. 60 , 61 , 62 Potential triggers include hormonal changes and hemodynamic fluctuations associated with pregnancy. 63 , 64 , 65 Lack of awareness of diagnosis and a potentially large underlying aortic aneurysm are known risks of aortic dissection in this population, especially type A dissection. 61 , 62 , 63 , 64 , 65 Other known or possible risk factors include specific PVs, family history of aortic dissection, multiparity, and breastfeeding or lactation. 66 , 67 , 68 , 69 , 70 Type B dissections associated with pregnancy may be as common as type A dissections and are largely unpredictable. 66 , 71 Finally, pregnancy may promote aortic aneurysm growth and a subsequent need for elective aortic root replacement. 69 Research involving pregnant persons is challenging because this is a vulnerable population. In addition, small numbers of pregnancies at individual centers make it difficult to conduct large, prospective trials to understand better the physiologic impact of pregnancy on short- and long-term aortic health. Thus, standardized data collection regarding reproductive health and pregnancy in individuals with TAD is essential to enable future collaborations and advance knowledge of maternal and fetal outcomes in these conditions, and thereby minimize the risk of aortic dissection. Several clinical studies have collected information about pregnancy outcomes in persons with TAD. 61 , 62 , 66 , 71 , 72 Important variables include the status of aortic disease, PVs, medical treatment, surveillance imaging before and during pregnancy, and cardiovascular, obstetric, and neonatal pregnancy outcomes. We propose that future clinical trials and registries utilize the following framework to harmonize methods for reproductive data collection from all women of childbearing age ( Table 14 ). We contend that the burden of including these elements is justified by enormous potential benefits to pregnant and peripartum women. A major goal is to refine clinical management based on more robust definitions of diameter thresholds for safe pregnancies within genotype categories, particularly among non-Marfan individuals. Aortic dissection associated with pregnancy should be defined as occurring during pregnancy and up to 12 weeks after pregnancy. Aortic dissection or the need for a surgery after 12 weeks postpartum should be recorded to evaluate the potential long-term burden associated with pregnancy. Table 14 Data Elements for Reproductive Outcomes Element Attributes Options Maternal age At termination, miscarriage, or birth Diagnosis TAD diagnosis before pregnancy Yes, no Preimplantation genetic testing Yes, no Pregnancy information Pregnancy number Yes, no In vitro fertilization Yes, no Cardiovascular or anticoagulant medications Total daily dose or equivalent a Delivery information Gestational age at birth Weeks Preterm birth (<37 weeks) No, spontaneous, iatrogenic Anesthesia for birth None, IV, regional, general Method of delivery Vaginal, operative vaginal, cesarean Pregnancy outcomes Termination Yes, no Miscarriage Yes, no Stillbirth (>20 weeks) Yes, no Live birth, singleton Yes, no Live birth, twins Yes, no Fetus or child affected Yes, no Extra-aortic complications Postpartum hemorrhage Yes, no Pre-eclampsia Yes, no Eclampsia Yes, no Uterine rupture Yes, no Uterine prolapse Yes, no 3°or 4° laceration/OASIS injury Yes, no Arrhythmia SVT, AF, NSVT, VT Venous thrombosis DVT, PE Neonatal complications Birthweight % Fetal anomalies Specify Breastfeeding or pumping (mo) No, 12 Aortic imaging Before pregnancy Measurement and Modality b First trimester Second trimester Third trimester Early postpartum (6 mo) Aortic complications Type A dissection Type B dissection Elective aortic repair Timing in relation to delivery, interventions c AF = atrial fibrillation; DVT = deep vein thrombosis; NSVT = non sustained ventricular tachycardia; PE = pulmonary embolism; SVT = supraventricular arrhythmia; TAD = thoracic aortic disease; VT = ventricular tachycardia. a Described in Medication and environmental exposures. b Described in Thoracic aortic measurements. c Described in Aortic interventions. Data Elements for Reproductive Outcomes AF = atrial fibrillation; DVT = deep vein thrombosis; NSVT = non sustained ventricular tachycardia; PE = pulmonary embolism; SVT = supraventricular arrhythmia; TAD = thoracic aortic disease; VT = ventricular tachycardia. Described in Medication and environmental exposures. Described in Thoracic aortic measurements. Described in Aortic interventions. The prevalence and severity of gynecologic health issues, such as endometriosis, fibroids, or abnormal uterine bleeding, are largely unexplored in the TAD population. Dysregulation of the transforming growth factor-beta pathway has been implicated in the mechanism of these gynecologic problems. 73 , 74 Organ cysts, including ovarian cysts, are more common in individuals with TAD. The prevalence and natural history of these cysts are unknown. In addition, there is a limited understanding of the effects of differential sex hormone exposures, including potential adverse effects of birth-control methods, through the lifetime and their influence on aortic health in women with TAD. Additional data elements may be collected to facilitate understanding of sex-specific hormonal impacts on aortic health in individuals with HTAD ( Table 15 ). Table 15 Data Elements for Hormonal Influences and Reproductive Health Element Attributes Options Menstrual cycles Age at menarche Years Age at menopause Years Hormonal contraception or hormone replacement therapies Estrogen patch or pill No, start date, stop date Combination contraceptive pill No, start date, stop date Progesterone only pill No, start date, stop date Depot or intramuscular progesterone No, start date, stop date Intrauterine devices Intrauterine device, progesterone No, start date, stop date Intrauterine device, copper No, start date, stop date Gynecologic problems Menorrhagia Yes, no Endometriosis Yes, no Fibroids Yes, no Ovarian cysts Yes, no Data Elements for Hormonal Influences and Reproductive Health

Dr Prakash was supported in part by a gift from the Genetic Aortic Disorders Association Canada. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.