Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown. A previous study implicated common variants in FBN1 with TAA disease risk. Here, we report a genome-wide scan of 1,351 TAA-affected individuals and 18,295 control individuals from the Cardiovascular Health Improvement Project and Michigan Genomics Initiative at the University of Michigan. We identified a genome-wide significant association with TAA for variants within the third intron of TCF7L2 following replication with meta-analysis of four additional independent cohorts. Common variants in this locus are the strongest known genetic risk factor for type 2 diabetes. Although evidence indicates the presence of different causal variants for TAA and type 2 diabetes at this locus, we observed an opposite direction of effect. The genetic association for TAA colocalizes with an aortic eQTL of TCF7L2, suggesting a functional relationship. These analyses predict an association of higher expression of TCF7L2 with TAA disease risk. In vitro, we show that upregulation of TCF7L2 is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease.

Postoperative acute kidney injury after thoracic endovascular aortic repair for acute type B aortic dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has evolved as the standard for treating complicated acute type B aortic dissection (ATBAD). Acute kidney injury (AKI) is a common complication in critically ill patients and is commonly observed in patients with ATBAD. The purpose of the study was to characterize AKI after TEVAR. METHODS: All patients who underwent TEVAR for ATBAD from 2011 through 2021 were identified using the International Registry of Acute Aortic Dissection. The primary end point was AKI. A generalized linear model analysis was performed to identify a factor associated with postoperative AKI. RESULTS: A total of 630 patients presented with ATBAD and underwent TEVAR. The indication for TEVAR was complicated ATBAD in 64.3%, high-risk uncomplicated ATBAD in 27.6%, and uncomplicated ATBAD in 8.1%. Of 630 patients, 102 (16.2%) developed postoperative AKI (AKI group) and 528 patients (83.8%) did not (non-AKI group). The most common indication for TEVAR was malperfusion (37.5%). In-hospital mortality was significantly higher in the AKI group (18.6% vs 4%; P < .001). Postoperatively, cerebrovascular accident, spinal cord ischemia, limb ischemia, and prolonged ventilation were more commonly observed in the AKI group. The expected mortality was similar at 2 years between the two groups (P = .51). Overall, the preoperative AKI was observed in 95 (15.7%) in the entire cohort consisting of 60 (64.5%) in the AKI group and 35 (6.8%) in the non-AKI group. A history of CKD (odds ratio, 4.6; 95% confidence interval, 1.5-14.1; P = .01) and preoperative AKI (odds ratio, 24.1; 95% confidence interval, 10.6-55.0; P < .001) were independently associated with postoperative AKI. CONCLUSIONS: The incidence of postoperative AKI was 16.2% in patients undergoing TEVAR for ATBAD. Patients with postoperative AKI had a higher rate of in-hospital morbidities and mortality than those without. A history of CKD and preoperative AKI were independently associated with postoperative AKI.

Editor's Choice - Trends in Management and Outcomes of Type B Aortic Dissection: A Report From the International Registry of Aortic Dissection.

OBJECTIVE: To describe the trends in management and outcomes of patients with acute type B aortic dissection in the International Registry of Acute Aortic Dissection. METHODS: From 1996 - 2022, 3 908 patients were divided into similar sized quartiles (T1, T2, T3, and T4). In hospital outcomes were analysed for each quartile. Survival rates following admission were compared using Kaplan-Meier analyses with Mantel-Cox Log rank tests. RESULTS: Endovascular treatment increased from 19.1% in T1 to 37.2% in T4 (ptrend < .001). Correspondingly, medical therapy decreased from 65.7% in T1 to 54.0% in T4 (ptrend < .001), and open surgery from 14.8% in T1 to 7.0% in T4 (ptrend < .001). In hospital mortality decreased in the overall cohort from 10.7% in T1 to 6.1% in T4 (ptrend < .001), as well as in medically, endovascularly and surgically treated patients (ptrend = .017, .033, and .011, respectively). Overall post-admission survival at three years increased (T1: 74.8% vs. T4: 77.3%; p = .006). CONCLUSION: Considerable changes in the management of acute type B aortic dissection were observed over time, with a significant increase in the use of endovascular treatment and a corresponding reduction in open surgery and medical management. These changes were associated with a decreased overall in hospital and three year post-admission mortality rate among quartiles.

Patients' and family members' views on pacemaker reuse: An international survey.

INTRODUCTION: The reuse of cardiac implantable electronic devices may help increase access to these therapies in low- and middle-income countries (LMICs). No published data exist regarding the views of patients and family members in LMICs regarding this practice. METHODS AND RESULTS: An article questionnaire eliciting attitudes regarding pacemaker reuse was administered to ambulatory adult patients and patients' family members at outpatient clinics at Centro Nacional Cardiologia in Managua, Nicaragua, Indus Hospital in Karachi, Pakistan, Hospital Carlos Andrade Marín, and Hospital Eugenio Espejo in Quito, Ecuador, and American University of Beirut Medical Center in Beirut, Lebanon. There were 945 responses (Nicaragua - 100; Pakistan - 493; Ecuador - 252; and Lebanon - 100). A majority of respondents agreed or strongly agreed that they would be willing to accept a reused pacemaker if risks were similar to a new device (707, 75%), if there were a higher risk of device failure compared with a new device (584, 70%), or if there were a higher risk of infection compared to a new device (458, 56%). A large majority would be willing to donate their own pacemaker at the time of their death (884, 96%) or the device of a family member (805, 93%). Respondents who were unable to afford a new device were more likely to be willing to accept a reused device (79% vs. 63%, p < .001). CONCLUSIONS: Patients and their family members support the concept of pacemaker reuse for patients who cannot afford new devices.

Spontaneous coronary artery dissection is infrequent in individuals with heritable thoracic aortic disease despite partially shared genetic susceptibility.

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), TGFBR2 (N = 2), TGFBR1 (N = 1), and PRKG1 (N = 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p = 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk.

Time of day does not influence outcomes in acute type A aortic dissection: Results from the IRAD.

BACKGROUND: Type A acute aortic dissection (TAAAD) represents a surgical emergency requiring intervention regardless of time of day. Whether such a "evening effect" exists regarding outcomes for TAAAD has not been previously studied using a large registry data. METHODS: Patients with TAAAD were identified from the International Registry of Acute Aortic Dissections (1996-2019). Outcomes were compared between patients undergoing operative repair during the daytime (D), defined as 8 am-5 pm, versus the evening (N), defined as 5 pm-8 am. RESULTS: Four thousand one-hundrd and ninety-seven surgically treated patients with TAAAD were identified, with 1824 patients undergoing daytime surgery (43.5%) and 2373 patients undergoing evening surgery (56.5%). Daytime patients were more likely to have undergone prior cardiac surgery (13.2% vs. 9.5%; p < .001) and have had a prior aortic dissection (4.8% vs. 3.4%; p = .04). Evening patients were more likely to have been transferred from a referring hospital (70.8% vs. 75.0%; p = .003). Daytime patients were more likely to undergo aortic valve sparing root procedures (23.3% vs. 19.2%; p = .035); however, total arch replacement was performed with equal frequency (19.4% vs. 18.8%; p = .751). In-hospital mortality (D: 17.3% vs. N. 16.2%; p = .325) was similar between both groups. Subgroup analysis examining the effect of weekend presentation revealed no significant mortality difference. CONCLUSIONS: A majority of TAAAD patients underwent surgical repair at night. There were higher rates of postoperative tamponade in evening patients; however, mortality was similar. The expertise of cardiac-dedicated operative and critical care teams regardless of time of day as well as training paradigms may explain similar mortality outcomes in this high risk population.

Insights From the International Registry of Acute Aortic Dissection: A 20-Year Experience of Collaborative Clinical Research.

Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.

Genetic Variants in LRP1 and ULK4 Are Associated with Acute Aortic Dissections.

Acute aortic dissections are a preventable cause of sudden death if individuals at risk are identified and surgically repaired in a non-emergency setting. Although mutations in single genes can be used to identify at-risk individuals, the majority of dissection case subjects do not have evidence of a single gene disorder, but rather have the other major risk factor for dissections, hypertension. Initial genome-wide association studies (GWASs) identified SNPs at the FBN1 locus associated with both thoracic aortic aneurysms and dissections. Here, we used the Illumina HumanExome array to genotype 753 individuals of European descent presenting specifically with non-familial, sporadic thoracic aortic dissection (STAD) and compared them to the genotypes of 2,259 control subjects from the Atherosclerosis Risk in Communities (ARIC) study matched for age, gender, and, for the majority of cases, hypertension. SNPs in FBN1, LRP1, and ULK4 were identified to be significantly associated with STAD, and these results were replicated in two independent cohorts. Combining the data from all cohorts confirmed an inverse association between LRP1 rs11172113 and STAD (p = 2.74 × 10(-8); OR = 0.82, 95% CI = 0.76-0.89) and a direct association between ULK4 rs2272007 and STAD (p = 1.15 × 10(-9); OR = 1.35, 95% CI = 1.23-1.49). Genomic copy-number variation analysis independently confirmed that ULK4 deletions were significantly associated with development of thoracic aortic disease. These results indicate that genetic variations in LRP1 and ULK4 contribute to risk for presenting with an acute aortic dissection.

Acute aortic syndromes: diagnosis and management, an update.

Acute aortic syndromes (AAS) encompass a constellation of life-threatening medical conditions including classic acute aortic dissection (AAD), intramural haematoma, and penetrating atherosclerotic aortic ulcer. Given the non-specific symptoms and physical signs, a high clinical index of suspicion is necessary to detect the disease before irreversible lethal complications occur. In order to reduce the diagnostic time delay, a comprehensive flowchart for decision-making based on pre-test sensitivity of AAS has been designed by the European Society of Cardiology guidelines on aortic diseases and should be thus applied in the emergency scenario. When the definitive diagnosis is made, prompt and appropriate therapeutic interventions should be undertaken if indicated by a highly specialized aortic team. Urgent surgery for AAD involving the ascending aorta (Type A) and medical therapy alone for AAD not involving the ascending aorta (Type B) are typically recommended. In complicated Type B AAD, thoracic endovascular aortic repair (TEVAR) is generally indicated. On the other hand, in uncomplicated Type B AAD, pre-emptive TEVAR rather than medical therapy alone to prevent late complications, while intuitive, requires further study in randomized cohorts. Finally, it should be highlighted that there is an urgent need to increase awareness of AAS worldwide, including dedicated education/prevention programmes, and to improve diagnostic and therapeutic strategies, outcomes, and lifelong surveillance.

External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry.

Aims: The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial. Methods and results: The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001). Conclusion: COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.

Endovascular thoracic aortic repair in confirmed or suspected genetically triggered thoracic aortic dissection.

OBJECTIVE: Endovascular repair in patients with connective tissues disorders is not recommended because of concern for repair failure. The aim of this study was to investigate thoracic endovascular aortic repair (TEVAR) outcomes in patients with confirmed or suspected syndromic and nonsyndromic genetically triggered thoracic aortic dissection. METHODS: We analyzed data for patients with descending thoracic aorta (DTA) dissection treated with TEVAR from the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Enrolled patients had confirmed (syndromic or familial) or suspected genetically triggered thoracic aortic disease. The latter group includes patients with sporadic aortic dissection presenting at 50 years of age or younger in the absence of a family history or syndromic features. RESULTS: Between 2006 and 2014, there were 371 patients with DTA dissection enrolled in GenTAC. TEVAR was performed in 31 cases (58.1% male; median age, 47 years; range, 21.3-65.6 years). Genetically triggered aortic dissection was confirmed in 18 cases, and an additional 13 cases had suspected genetically triggered dissection because of early onset of presentation. TEVAR was performed in nine patients with type A aortic dissection: five in conjunction with acute type A dissection repair and four in the chronic phase to treat aneurysmal degeneration of the residual dissected DTA (median interval to TEVAR, 2.1 years). TEVAR was also performed in 22 cases of type B aortic dissection (TBAD), 12 acute and 10 chronic (median interval to TEVAR, 1.6 years). There were no perioperative deaths. Median follow-up for all cases was 2 years (range, 0.4 month-7 years). Reinterventions after TEVAR were performed in 13 cases (41.9%). This included urgent repair of three retrograde ascending aorta dissections occurring after TEVAR for acute TBAD (25%) and seven thoracoabdominal repairs with stent graft explantation (22.6%) at a median of 7 months after TEVAR (range, 1-16.6 months). CONCLUSIONS: TEVAR in patients with genetically triggered aortic dissections can be lifesaving in the acute setting though associated with high risk of retrograde aortic dissection in acute TBAD. For chronic dissection-related DTA aneurysmal degeneration, TEVAR could potentially be lifesaving in patients deemed too high risk for open surgical repair. Close postoperative surveillance is required, given the risk of subsequent device failure and need for reintervention. Because these circumstances are rare, multicenter prospective enrollment of patients with genetically triggered aortic disease is essential to delineate the indications for and risks of TEVAR in this heterogeneous population.

Current evidence in predictors of aortic growth and events in acute type B aortic dissection.

OBJECTIVES: Acute type B aortic dissection can have a stable course or evolve into aneurysm and subsequent adverse events. The aim of this systematic review was to analyze the morphologic predictors of an adverse course to establish their validity based on consistency of results. METHODS: Fifty-one studies were included in this review, reporting on aortic size, false lumen (FL) size, primary entry tear (ET) size and location, status of FL thrombosis, number of ETs, branch vessels involvement, and FL longitudinal extent. RESULTS: Some predictors showed good consistency, whereas others did not. Aortic size was the most investigated predictor. A larger diameter at presentation predicted worse outcomes, with few exceptions. Both FL size and size relative to true lumen size also predicted an adverse course, although a standardized measurement method was not used. Regarding primary ET size and location, evidence was sparse and somewhat conflicting. Although FL complete thrombosis was consistently associated with a more benign course, the role of partial thrombosis remained unclear and the concept of FL saccular formation might account for the inconsistency, but further evidence is needed. A higher number of re-entry tears was considered to be protective against false channel expansion, but results need to be confirmed. The predictive role of branch vessels involvement and FL longitudinal extent remain controversial. CONCLUSIONS: Among several predictors of aortic growth and events in acute type B aortic dissection, controversial and even conflicting results have been described. Consistent evidence has been demonstrated only for two predictors: aortic size at presentation is associated with adverse events and total FL thrombosis has a protective role.

Worldwide pacemaker and defibrillator reuse: Systematic review and meta-analysis of contemporary trials.

BACKGROUND: Patients go without pacemaker, defibrillator, and cardiac resynchronization therapies (devices) each year due to the prohibitive costs of devices. OBJECTIVE: We sought to examine data available from studies regarding contemporary risks of reused devices in comparison with new devices. METHODS: We searched online indexing sites to identify recent studies. Peer-reviewed manuscripts reporting infection, malfunction, premature battery depletion, and device-related death with reused devices were included. The primary study outcome was the composite risk of infection, malfunction, premature battery depletion, and death. Secondary outcomes were the individual risks. RESULTS: Nine observational studies (published 2009-2017) were identified totaling 2,302 devices (2,017 pacemakers, 285 defibrillators). Five controlled trials were included in meta-analysis (2,114 devices; 1,258 new vs 856 reused). All device reuse protocols employed interrogation to confirm longevity and functionality, disinfectant therapy, and, usually, additional biocidal agents, packaging, and ethylene oxide gas sterilization. Demographic characteristics, indications for pacing, and median follow-up were similar. There were no device-related deaths reported and no statistically significant difference in risk between new versus reused devices for the primary outcome (2.23% vs 3.86% respectively, P = 0.807, odds ratio = 0.76). There were no significant differences seen in the secondary outcomes for the individual risks of infection, malfunction, and premature battery depletion. CONCLUSIONS: Device reuse utilizing modern protocols did not significantly increase risk of infection, malfunction, premature battery depletion, or device-related death in observational studies. These data provide rationale for proceeding with a prospective multicenter noninferiority randomized control trial.

Impact of Left Subclavian Artery Revascularization before Thoracic Endovascular Aortic Repair on Postoperative Cerebrovascular Hemodynamics.

BACKGROUND: The impact of left subclavian artery (LSA) revascularization before thoracic endovascular aortic repair (TEVAR) on cerebrovascular flow is not well described. We studied bilateral vertebral and carotid artery flow characteristics before and after TEVAR to evaluate the hemodynamic effects of LSA revascularization. METHODS: Seventy-four patients with mixed etiologies (mean age 70.9 ± 10.5 years) underwent LSA revascularization and TEVAR (2006-2016) and had available preoperative and postoperative carotid duplex study available. Data from patient demographics, procedures, preoperative, and postoperative carotid duplex studies were gathered. Revascularization was by left common carotid artery (LCCA) to LSA bypass (n = 70, 94.6%) or LSA to LCCA transposition (n = 4, 5.4%). RESULTS: Duplex confirmation of antegrade left vertebral artery (LVA) flow decreased significantly after TEVAR with LSA revascularization (100.0% vs. 77.9%, P < 0.001). Incidence of retrograde LVA flow increased from 0.0% to 8.3% (P = 0.063). Postoperatively, LVA bidirectional flow was observed in 3 patients (4.4%). Flow directions in the right vertebral artery (RVA) did not change significantly. Peak systolic velocity (PSV) in the LVA decreased significantly after TEVAR from 55.1 ± 22.0 cm/s to 35.9 ± 26.3 cm/s (P < 0.001). In contrast, PSV increased in the RVA and the right internal carotid artery (ICA; 52.2 ± 21.7 cm/s to 63.2 ± 23.3 cm/s, P = 0.012 and 95.3 ± 46.8 cm/s to 102.8 ± 42.9 cm/s, P = 0.011). PSV did not change significantly in the left ICA. At mean follow-up of 36.6 ± 26.8 months, primary bypass patency was 100.0%. Postoperatively, one case of temporary spinal cord ischemia was seen (1.4%). Stroke rate was 6.9% (n = 5, 100.0% embolic), all without permanent disabilities. Stroke circulation distribution was 60.0% posterior, 20.0% anterior, and 20.0% mixed. Location of stroke was left sided (n = 2) or in both hemispheres (n = 3). There were no deaths at 30 days. Neurological events during follow-up included 3 new strokes. All-cause mortality rate during follow-up was 12.2% (n = 9). CONCLUSIONS: Adjunctive LSA revascularization in the setting of zone 2 TEVAR coverage is associated with hemodynamic vertebral artery changes. Future studies in larger sample sizes should evaluate whether these novel findings are an important determinant of postoperative neurologic events.

Medication adherence patterns in aortic dissection survivors.

BACKGROUND & OBJECTIVES: Beta-blockers have been shown to improve survival in both type A and type B acute aortic dissection (AAD) patients. Calcium channel blockers have been shown to selectively improve survival only in type B AAD patients. There is a lack of data on medication adherence in AAD survivors. The purpose of this study was to assess medication adherence in patients who survived an AAD. METHODS: This was a cross-sectional survey-based study of individuals from a single medical centre which was part of the larger International Registry of Acute Aortic Dissection (IRAD). Patients with type A or B AAD who survived to discharge were included in this study. Individuals who were deceased based on the results of an online Social Security Death Index were excluded from the study. Data were obtained from both a survey and also from abstraction from the local academic institution's IRAD registry. A survey packet was sent to patients. One section of this survey was dedicated to assessing medication adherence using the 4-item Morisky scale. RESULTS: Eighty two completed surveys were returned; 74 patients completed the section of the survey pertaining to medication adherence (response rate 38%). Morisky score was ≥1.0 for 27 (36%) patients and 0 for 47 (64%) patients. Thirty three patients reported yes to 'forget to take medications' and eight reported yes to 'careless with medications.' Medication non-adherence (defined as a score of ≥1.0 on Morisky) was associated with increased follow up recurrence of chest pain at one year of follow up. Only two patients stopped their antihypertensive on their own and did not cite a reason for doing this. INTERPRETATION & CONCLUSIONS: The medication adherence rate for patients who survived an AAD was 64 per cent at a median (Q1, Q3) of 7.1 yr (5.6, 11.5) after discharge, as per the Morisky scale. The clinicians should educate their patients on the importance of antihypertensive therapy and assess for forgetfulness and carelessness at each clinic visit, as well as understand patients' beliefs about drug therapy, all of which have been shown to increase medication adherence.

Recurrent Aortic Dissection: Observations From the International Registry of Aortic Dissection.

BACKGROUND: Improved medical care after initial aortic dissection (AD) has led to increased survivorship and a population of individuals at risk for further cardiovascular events, including recurrent AD. Reports describing recurrent ADs have been restricted to small numbers of patients from single institutions. We used the IRAD (International Registry of Acute Aortic Dissection) database to examine the clinical profiles and outcomes of patients with recurrent AD. METHODS: We identified 204 patients enrolled in IRAD with recurrent AD. For the primary analysis, patient characteristics, interventions, and outcomes were analyzed and compared with 3624 patients with initial AD. Iterative logistic modeling was performed to investigate variables associated with recurrent AD. Cox regression analyses were used to determine variables associated with 5-year survival. A subset of recurrent AD patients was analyzed for anatomic and demographic details of initial and recurrent ADs. RESULTS: Patients with recurrent AD were more likely to have Marfan syndrome (21.5% versus 3.1%; P<0.001) but not bicuspid aortic valve (3.6% versus 3.2%; P=0.77). Descending aortic dimensions were greater in patients with recurrent AD than in patients with initial AD independently of sentinel dissection type (type A: 4.3 cm [3.5-5.6 cm] versus 3.3 cm [2.9-3.7 cm], P<0.001; type B: 5.0 cm [3.9-6.0 cm] versus 4.0 cm [3.5-4.8 cm], P<0.001), and this observation was accentuated among patients with Marfan syndrome. In multivariate analysis, the diagnosis of Marfan syndrome independently predicted recurrent AD (hazard ratio, 8.6; 95% confidence interval, 5.8-12.8; P<0.001). Patients with recurrent AD who presented with proximal followed by distal AD were younger than patients who experienced distal followed by proximal dissection AD (42.1±16.1 versus 54.3±14.8 years; P=0.004). CONCLUSIONS: Among those suffering acute aortic dissection, 5% have a history of a prior aortic dissection. Recurrent AD is strongly associated with Marfan syndrome.