Acute aortic dissection.

Although substantial progress has been made in the prevention, diagnosis, and treatment of acute aortic dissection, it remains a complex cardiovascular event, with a high immediate mortality and substantial morbidity in individuals surviving the acute period. The past decade has allowed a leap forward in understanding the pathophysiology of this disease; the existing classifications have been challenged, and the scientific community moves towards a nomenclature that is likely to unify the current definitions according to morphology and function. The most important pathophysiological pathway, namely the location and extension of the initial intimal tear, which causes a disruption of the media layer of the aortic wall, together with the size of the affected aortic segments, determines whether the patient should undergo emergency surgery, an endovascular intervention, or receive optimal medical treatment. The scientific evidence for the management and follow-up of acute aortic dissection continues to evolve. This Seminar provides a clinically relevant overview of potential prevention, diagnosis, and management of acute aortic dissection, which is the most severe acute aortic syndrome.

Branched and fenestrated endovascular aortic arch repair in patients with native proximal aortic landing zone.

OBJECTIVE: Fenestrated and branched thoracic endovascular repair (f/bTEVAR) have been successfully applied in patients with diverse aortic arch pathologies. The aim of this study is to present the early and mid-term outcomes of patients with native proximal aortic landing (NPAL) managed with f/bTEVAR. METHODS: A single-center retrospective analysis of patients with NPAL, managed with f/bTEVAR, between September 1, 2011, and June 30, 2022, was conducted. All patients were treated with custom-made devices (Cook Medical) with landing within Ishimaru zones 0 to 2. Primary outcomes were technical success, mortality, stroke, and retrograde type A dissection at 30 days. Follow-up outcomes were considered secondary. RESULTS: A total of 126 patients were included (69.8% males; mean age, 70.8 ± 4.2 years; 18.3% urgent). The main indications (60.4%) for repair were aortic arch (29.4%) and thoracoabdominal aortic aneurysms (31.0%). Seventy-two patients (57.1%) were managed with fTEVAR. Proximal landing in zone 0 and 1 was chosen in 97.6%. Technical success was 94.4%, and 30-day mortality was 11.9%. Strokes were diagnosed in 13.5% of patients and major strokes were identified in 7.9% cases. Retrograde type A dissection rate was 3.9%. The multivariate analysis confirmed landing in Ishimaru zone 0 as an independently related factor for stroke (P = .005), whereas stroke (P < .001), pericardial effusion (P < .001), and acute kidney injury (P < .001) were independently related to 30-day mortality. Mean follow-up was 17.5 ± 9.3 months. The estimated survival rate and the freedom from reintervention rate were 72.6% (standard error, 4.4%) and 46.4% (standard error, 6.0%) at 24-month follow-up, respectively. CONCLUSIONS: Stroke rate after endovascular arch repair was alarming among patients with NPAL. Proximal landing to zone 0 was related to higher risk of stroke. Reinterventions were common within the 24-month follow-up.

PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods.

BACKGROUND: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. AIMS: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). METHODS: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. DESIGN: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. PROCESSES: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. ASSESSMENTS: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. DISCUSSION OF THE DESIGN: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. CONCLUSION: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.

Longitudinal follow-up by MR angiography reveals progressive dilatation of the distal aorta after aortic root replacement in Marfan syndrome.

OBJECTIVES: To define and compare growth rates of the distal aorta in Marfan patients with and without aortic root replacement using serial MR angiography (MRA). METHODS: We retrospectively included 136 Marfan patients with a total of 645 MRAs who underwent a median of five MRAs (range: 2-13) at 1.5 T and 3 T in annual intervals. Of these, 41 patients (34.8 ± 12 years) had undergone aortic root replacement. The remaining 95 patients (29.0 ± 17 years) still had a native aorta and served as the control group. Thoracic aortic diameters were independently measured at eleven predefined levels. Estimated growth rates were calculated using a mixed effects model adjusted for sex, age, BMI, and medication. RESULTS: Marfan patients with aortic root replacement revealed the highest mean estimated growth rate in the proximal descending aorta (0.77 mm/year, CI: 0.31-1.21). Mean growth rates at all levels of the distal thoracic aorta were significantly higher in patients with aortic root replacement (0.28-0.77 mm/year) when compared to patients without aortic root replacement (0.03-0.07 mm/year) (all p < 0.001). Antihypertensive medication, gender, and BMI had no significant impact on the distal aortic growth rates. CONCLUSION: Distal thoracic aortic diameters increase at a significantly higher rate in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. Further studies are warranted to investigate if the increased growth rate of the distal thoracic aorta after aortic root replacement is caused by altered hemodynamics due to the rigid aortic root graft or due to the general genetic disposition of post-operative Marfan patients. CLINICAL RELEVANCE STATEMENT: High growth rates of the distal aorta after aortic root replacement underline the need for careful life-long aortic imaging of Marfan patients after aortic root replacement. KEY POINTS: • Aortic growth rates in Marfan patients with aortic root replacement are highest in the mid-aortic arch, the proximal- and mid-descending aorta. • Growth rates of the distal thoracic aorta are significantly higher in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. • Antihypertensive medication, gender, and BMI have no significant impact on distal aortic growth rates in Marfan patients.

Assessment of aortic diameter in Marfan patients: intraindividual comparison of 3D-Dixon and 2D-SSFP magnetic resonance imaging.

OBJECTIVES: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients. METHODS: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods. RESULTS: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002). CONCLUSION: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root. KEY POINTS: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations.

Endovascular Options for the Ascending Aorta and Aortic Arch: A Scoping Review.

The gold standard for aneurysmal repair of the ascending aorta and the aortic arch has been open surgery with an established track record of good results in suitable patients. In recent years, with innovations in the endovascular field alternative endovascular solutions for pathologies of the aortic arch and ascending aorta became available. At first reserved only for highly selected patients unfit for open surgery, endovascular aortic arch repair is now being offered to patients with suitable anatomy in high-volume referral centers after discussion in an interdisciplinary team. The present scoping review aims at providing an overview on indications, available devices, technical aspects, and feasibility studies of endovascular arch repair both in elective and emergent situations, including also experiences and considerations from our center.

Safety and Effectiveness of TEVAR in Native Proximal Landing Zone 2 for Chronic Type B Aortic Dissection in Patients With Genetic Aortic Syndrome.

OBJECTIVES: The aim of this study is to report the safety and effectiveness of thoracic endovascular aortic repair (TEVAR) in a native proximal landing zone (PLZ) 2 for chronic type B aortic dissection (TBAD) patients with genetic aortic syndrome (GAS). METHODS: A retrospective review of a single center database to identify patients with GAS treated with TEVAR in native PLZ 2 for chronic TBAD and thoracic false lumen aneurysm between February 2012 and February 2018 was undertaken. RESULTS: In total, 31 patients with GAS (24 Marfan syndrome [MFS], 5 Loeys-Dietz syndrome [LDS], and 2 vascular Ehlers-Danlos syndrome [vEDS]) were treated by endovascular repair. Nineteen patients were treated by TEVAR as index procedures with 8 patients (5 females, mean age = 55, range = 36-79 years old) receiving TEVAR in native PLZ 2. Left subclavian artery (LSA) perfusion was preserved in all 8 patients: by left common carotid artery-LSA bypass in 6 patients, chimney stenting of the LSA in 1 patient, and partial coverage of LSA ostium in 1 patient. Technical success was achieved in all patients (100%). There was no 30 day mortality (0%). The 30 day morbidity (0%) was free from major complications. The median follow-up was 40 months (range = 7-79). One patient died due to non-aortic-related cause. Native PLZ 2 was free from complications in MFS patients (5/8). Two patients with LDS developed type Ia endoleak with aneurysmal progression. One patient was treated by proximal extension with a double inner branched arch stent-graft landing in the replaced ascending aorta. The other one was treated with frozen elephant trunk. CONCLUSION: Thoracic endovascular aortic repair in native PLZ 2 was safe and effective with no early or midterm PLZ complications in patients with MFS with chronic TBAD in this limited series. Native PLZ 2 is not safe in patients with LDS and should only be used in emergencies as a bridging to open repair.

Endovascular Treatment of Aortic Pathologies in Patients With Marfan Syndrome: Single-Center Experience.

OBJECTIVES: To study the outcome of endovascular treatment of aortic pathologies in patients with Marfan syndrome (MFS) at a single institution. METHODS: Consecutive MFS patients who underwent endovascular repair or hybrid procedures for aortic pathologies from January 2010 to May 2020 were identified. Several endovascular and hybrid strategies have been used. Technical success, short- and mid-term survival, complications, and re-interventions were retrospectively analyzed. RESULTS: During the study period, 24 patients with MFS (median age, 48 [13-78] years; 58% males) were treated. Indications for intervention were chronic aortic dissection with aneurysm degeneration in 16 patients (67%), acute type B aortic dissection in 4 patients (17%), aortic aneurysm without any dissection in 3 patients (13%), and aortic intramural hematoma in 1 patient (4%). Most patients were asymptomatic (83%), three (13%) were symptomatic and one (4%) had a contained rupture. The median aneurysm diameter was 56 (35-86) mm. Hybrid procedures were performed in 7 (29%) patients. Thoracic endovascular repair was performed in 12 (50%) patients, a fenestrated or branched endovascular aortic repair in 4 (17%) patients, and placement of an iliac artery stent-graft in 1 (4%) patient. Procedures were staged in 12 (50%) patients. Technical success was achieved in all patients. The median intensive care unit stay was 6 (range, 1-30) days, and the median hospital stay was 23 (range, 3-112) days. Early mortality was reported in 1 (4%) patient. Wound infection was seen in 7 (29%) patients and gastrointestinal complications in 3 (13%) patients. The median follow-up was 42 (range, 1-127) months. The cumulative survival rate was 87% at 24 months. The cumulative freedom from re-intervention was 77% at 12 months. CONCLUSIONS: Endovascular treatment of aortic pathologies in patients with MFS appears feasible with acceptable early and mid-term outcomes in terms of mortality and re-intervention rates. Endovascular therapy plays an increasing role in MFS patients with aortic pathology.

Management of Ascending Aorta and Aortic Arch: Similarities and Differences Among Cardiovascular Guidelines.

BACKGROUND: Ascending aorta and aortic arch diseases have an increasing interest among cardiovascular specialists regarding diagnosis and management. Innovations in endovascular surgery and evolution of open surgery have extended the indications for treatment in patients previously considered unfit for surgery. The aim of this systematic review of the literature was to present and analyze current cardiovascular guidelines for overlap and differences in their recommendations regarding ascending aorta and aortic arch diseases and the assessment of evidence. METHODS: The English medical literature was searched using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from January 2009 to December 2020. Recommendations on selected topics were analyzed, including issues from definitions and diagnosis (imaging and biomarkers) and indications for treatment to management, including surgical techniques, of the most important ascending aorta and aortic arch diseases. RESULTS: The initial search identified 2414 articles. After exclusion of duplicate or inappropriate articles, the final analysis included 5 articles from multidisciplinary, cardiovascular societies published between 2010 and 2019. The definition of non-A-non-B aortic dissection is lacking from most of the guidelines. There is a disagreement regarding the class of recommendation and level of evidence for the diameter of ascending aorta as an indication. The indication for treatment of aortic disease may be individualized in specific cases while the growth rate may also affect the decision making. The role of endovascular techniques has not been established in current guidelines except by 1 society. Supportive evidence level in the management of aortic arch diseases remains limited. CONCLUSION: In current recommendations of cardiovascular societies, the ascending aorta and aortic arch remain a domain of open surgery despite the introduction of endovascular techniques. Recommendations of the included societies are mostly based on expert opinion, and the role of endovascular techniques has been highlighted only from 1 society. The chronological heterogeneity apparent among guidelines and the inconsistency in evidence level should be also acknowledged. More data are needed to develop more solid recommendations for the ascending aorta and aortic arch diseases.

Tricuspid valve prolapse as an early predictor for severe phenotype in children with Marfan syndrome.

AIM: In Marfan syndrome, various cardiovascular pathologies, such as aortic dilatation and mitral valve pathologies, already occur in childhood and determine course of the disease. This study aimed to establish additional cardiovascular risk markers for severe Marfan phenotypes. We investigated tricuspid valve prolapse (TVP) and its predictive value for outcome of paediatric Marfan disease. METHODS: In this retrospective, observational cohort study, we identified 130 paediatric Marfan patients (10.7 ± 4.8 years) with FBN1 variants. We divided patients into two groups based on TVP presence and performed a cross-sectional analysis to investigate the association of TVP with other cardiovascular, ocular and systemic pathologies, at first and last visit. A longitudinal analysis was performed with follow-up data. RESULTS: At baseline, patients with TVP had higher incidence of aortic root dilatation (p = 0.013), mitral valve prolapse (p = 0.0001) and systemic manifestations (p = 0.025) than patients without TVP. At follow-up, previous presence of TVP predicted higher probability of aortic root dilatation (p = 0.002), mitral valve prolapse (p = 0.0001) and systemic manifestations (p = 0.002). CONCLUSION: This shows that TVP is linked to both cardiac and extracardiac Marfan manifestations and TVP is an important marker for a disease severity in these children. Therefore, TVP should be assessed routinely using echocardiography in paediatric Marfan patients.

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. METHODS: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. RESULTS: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts. CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.

The CatLet score and outcome prediction in acute myocardial infarction for patients undergoing primary percutaneous intervention: A proof-of-concept study.

BACKGROUND: The Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score accommodating the variability in coronary anatomy is a recently developed and comprehensive angiographic scoring system aimed at assisting in risk-stratification of patients with coronary artery disease. However, a validation of this angiographic scoring system is lacking. METHODS: The CatLet score was calculated retrospectively in 308 consecutively enrolled patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention. The primary endpoint, major adverse cardiac or cerebrovascular events (MACCEs), was stratified according to CatLet tertiles: CatLetlow ≤14 (n = 124), CatLetmid 15-21 (n = 82) and CatLettop ≥22 (n = 102). RESULTS: The CatLet score alone or after adjusting for a broad spectrum of risk factors, significantly predicted clinical outcomes at a median 4.3-year follow-up. Multivariable-adjusted hazard ratios (95%CI)/unit higher score were 1.05 (1.04-1.07) for MACCE, 1.06 (1.04-1.07) for cardiac death, and 1.05 (1.04-1.07) for all-cause death. When compared to the SYNTAX score, improved discrimination and better calibration of this CatLet score resulted in a significantly refined risk stratification. The overall category-free net reclassification improvement afforded by this CatLet score was as follows: 37.2% (p = .008) for MACCEs, 35.5% (p = .0249) for cardiac death, and 31.8% (p = .0316) for all-cause death. CONCLUSIONS: The ability to integrate the variability in coronary anatomy into angiographic scoring makes the CatLet score a more specific tool for outcome predictions in AMI. (http://www.chictr.org.cn. Unique identifiers: ChiCTR-POC-17013536).

4D flow cardiovascular magnetic resonance for monitoring of aortic valve repair in bicuspid aortic valve disease.

BACKGROUND: Aortic valve repair has become a treatment option for adults with symptomatic bicuspid (BAV) or unicuspid (UAV) aortic valve insufficiency. Our aim was to demonstrate the feasibility of 4D flow cardiovascular magnetic resonance (CMR) to assess the impact of aortic valve repair on changes in blood flow dynamics in patients with symptomatic BAV or UAV. METHODS: Twenty patients with adult congenital heart disease (median 35 years, range 18-64; 16 male) and symptomatic aortic valve regurgitation (15 BAV, 5 UAV) were prospectively studied. All patients underwent 4D flow CMR before and after aortic valve repair. Aortic valve regurgitant fraction and systolic peak velocity were estimated. The degree of helical and vortical flow was evaluated according to a 3-point scale. Relative flow displacement and wall shear stress (WSS) were quantified at predefined levels in the thoracic aorta. RESULTS: All patients underwent successful aortic valve repair with a significant reduction of aortic valve regurgitation (16.7 ± 9.8% to 6.4 ± 4.4%, p < 0.001) and systolic peak velocity (2.3 ± 0.9 to 1.9 ± 0.4 m/s, p = 0.014). Both helical flow (1.6 ± 0.6 vs. 0.9 ± 0.5, p < 0.001) and vortical flow (1.2 ± 0.8 vs. 0.5 ± 0.6, p = 0.002) as well as both flow displacement (0.3 ± 0.1 vs. 0.25 ± 0.1, p = 0.031) and WSS (0.8 ± 0.2 N/m2 vs. 0.5 ± 0.2 N/m2, p < 0.001) in the ascending aorta were significantly reduced after aortic valve repair. CONCLUSIONS: 4D flow CMR allows assessment of the impact of aortic valve repair on changes in blood flow dynamics in patients with bicuspid aortic valve disease.

Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients.

PURPOSE: Heritable factors play an important etiologic role in connective tissue disorders (CTD) with vascular involvement, and a genetic diagnosis is getting increasingly important for gene-tailored, personalized patient management. METHODS: We analyzed 32 disease-associated genes by using targeted next-generation sequencing and exome sequencing in a clinically relevant cohort of 199 individuals. We classified and refined sequence variants according to their likelihood for pathogenicity. RESULTS: We identified 1 pathogenic variant (PV; in FBN1 or SMAD3) in 15 patients (7.5%) and ≥1 likely pathogenic variant (LPV; in COL3A1, FBN1, FBN2, LOX, MYH11, SMAD3, TGFBR1, or TGFBR2) in 19 individuals (9.6%), together resulting in 17.1% diagnostic yield. Thirteen PV/LPV were novel. Of PV/LPV-negative patients 47 (23.6%) showed ≥1 variant of uncertain significance (VUS). Twenty-five patients had concomitant variants. In-depth evaluation of reported/calculated variant classes resulted in reclassification of 19.8% of variants. CONCLUSION: Variant classification and refinement are essential for shaping mutational spectra of disease genes, thereby improving clinical sensitivity. Obligate stringent multigene analysis is a powerful tool for identifying genetic causes of clinically related CTDs. Nonetheless, the relatively high rate of PV/LPV/VUS-negative patients underscores the existence of yet unknown disease loci and/or oligogenic/polygenic inheritance.

Single-center experience with an inner branched arch endograft.

OBJECTIVE: Whereas open repair is the "gold standard" for most aortic arch diseases, a subgroup of patients might benefit from an endovascular approach. The introduction of branched stent grafts with dedicated design to address the challenges of the ascending aorta and the aortic arch has opened an entirely new area of treatment for these patients. We investigated the early outcomes of branched thoracic endovascular aortic repair (b-TEVAR) in various types of disease of the aortic arch. METHODS: A retrospective analysis was conducted of prospectively collected data from a single center of all consecutive patients treated with b-TEVAR. The indication for elective endovascular repair was consented in an interdisciplinary case conference. All patients were treated with a custom-made inner branched arch endograft with two internal branches (Cook Medical, Bloomington, Ind) and left-sided carotid-subclavian bypass. Study end points were technical success, 30-day mortality, and complications as well as late complications and reinterventions. RESULTS: Between 2012 and 2017, there were 54 patients (38 male; median age, 71 years) treated with diseases of the aortic arch. Indications for therapy involved degenerative aortic arch or proximal descending aortic aneurysms requiring arch repair (n = 24), dissection with or without false lumen aneurysms (n = 26), and penetrating aortic ulcers (n = 4). Forty-three cases (80%) were performed electively and 11 urgently for contained ruptures (n = 3) or symptomatic aneurysms (n = 8) with endografts already available for the patient or with grafts of other patients with similar anatomy. Technical success was achieved in 53 cases (98%). The 30-day mortality and major stroke incidence were 5.5% (3/54) and 5.5% (3/54), respectively; in-hospital mortality was 7.4% (n = 4), and minor strokes (including asymptomatic new cerebral lesions) occurred in 5.5% (n = 3). There were two cases of transient spinal cord ischemia with complete recovery and one of paraplegia. No retrograde type A dissections or cardiac injuries were observed. Three early stent graft-related reinterventions were necessary to correct proximal endograft kinking with type IA endoleak in one patient, a bridging stent graft stenosis in another patient, and false lumen persistent perfusion from dissected supra-aortic vessels in the last patient. Mean in-hospital stay was 14 ± 8 days. During a mean follow-up of 12 ± 9 months, three nonaorta-related deaths and one aorta-related death distal to the arch repair were observed. CONCLUSIONS: Treatment of aortic arch diseases with b-TEVAR is feasible and safe with acceptable mortality and stroke rates.

A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. METHODS: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. RESULTS: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). CONCLUSIONS: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

Endovascular Repair of Ascending Aortic Pathologies With Tubular Endografts: A Single-Center Experience.

Purpose: To investigate the endovascular treatment of ascending aortic pathologies of high-risk patients unsuitable for open repair. Materials and Methods: From 2010 to 2017, 24 patients (mean age 70±15 years, range 29-90; 18 men) were treated at a single center for various pathologies of the ascending aorta, including acute or chronic type A aortic dissections (n=16), pseudoaneurysms (n=6), fixation of a dislocated percutaneous aortic valve (n=2), and miscellaneous indications (n=3). The patients were selected following an interdisciplinary case evaluation, attended by cardiologists and cardiac and vascular surgeons. The Zenith Ascend TAA Endovascular Graft was implanted; simultaneous procedures were performed in 13 patients. Of the total 27 Ascend TEVAR procedures (24 primary and 3 reinterventions), 17 were performed urgently and 10 electively. The primary outcome measure was 30-day survival. The secondary outcomes were cardiovascular complications, midterm survival, and reintervention rate. Results: Clinical success was achieved in all but 1 case. The 30-day survival was 79% (19/24); of the 5 deaths only 1 was directly related to the endograft implanted. In the 30-day postoperative period, there was 1 myocardial infarction, 2 major strokes, a mycotic pseudoaneurysm, a case of Ascend TEVAR-induced high-grade aortic insufficiency, and a minor stroke; 1 patient developed paraplegia after concurrent implantation of a 4-branched abdominal stent-graft. Two patients had a reintervention within 30 days for the pseudoaneurysm and the aortic insufficiency, respectively. During a mean follow-up of 11 months (0-35 months), there was 1 late death (cancer) and 1 additional reintervention at 10 months for a late type Ia endoleak (12.5% reintervention rate). Conclusion: Endovascular repair of ascending aortic pathologies with stent-grafts is a feasible treatment option with acceptable early and midterm outcomes in high-risk patients unsuitable for open surgery. The complexity of Ascend TEVAR might justify higher reintervention rates.

Ocular manifestation in Marfan syndrome: corneal biomechanical properties relate to increased systemic score points.

PURPOSE: To evaluate corneal deformation to an air puff as a new noninvasive tool to document disease status in Marfan syndrome (MFS) METHODS: Prospective observational cohort study. We included patients diagnosed with MFS who had their routine cardiovascular follow-up and applied the revised Ghent nosology to define two subgroups according to a high (≥ 7) and a low (< 7 points) systemic score. Dynamic Scheimpflug-based biomechanical analyses (CorvisST® [CST; Oculus GmbH]) were performed. The main outcome measure was the displacement of the corneal apex as given by the parameters highest concavity (HC; in ms), peak distance (PD; in mm), and highest concavity deformation amplitude (DA; mm). RESULTS: Forty-three eyes of 43 individuals (19 female, 24 male; mean age 42.0 ± 12.0 years, range 18-67 years) diagnosed with MFS were included. Applying the Ghent criteria, 21 patients had an advanced systemic score of ≥ 7, and 22 had score points < 7. There were no differences in age or sex between both groups. In contrast, HC was faster (P = 0.004), and PD (P < 0.001) was longer in those individuals with systemic score ≥ 7; maximum DA did not result in a statistically significant difference between the groups (P = 0.250). CONCLUSIONS: In vivo noninvasive biomechanical analyses with CST offer a new, non-invasive method to identify pathologic corneal deformation responses in adults with MFS. In the future, corneal deformation to an air puff could thus assist early identification of patients with high Ghent score as an adjunct to existing diagnostic tests.

Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.

BACKGROUND: Genetic FBN1 testing is pivotal for confirming the clinical diagnosis of Marfan syndrome. In an effort to evaluate variant causality, FBN1 databases are often used. We evaluated the current databases regarding FBN1 variants and validated associated phenotype records with a new Marfan syndrome geno-phenotyping tool called the Marfan score. METHODS AND RESULTS: We evaluated four databases (UMD-FBN1, ClinVar, the Human Gene Mutation Database (HGMD), and Uniprot) containing 2,250 FBN1 variants supported by 4,904 records presented in 307 references. The Marfan score calculated for phenotype data from the records quantified variant associations with Marfan syndrome phenotype. We calculated a Marfan score for 1,283 variants, of which we confirmed the database diagnosis of Marfan syndrome in 77.1%. This represented only 35.8% of the total registered variants; 18.5-33.3% (UMD-FBN1 versus HGMD) of variants associated with Marfan syndrome in the databases could not be confirmed by the recorded phenotype. CONCLUSION: FBN1 databases can be imprecise and incomplete. Data should be used with caution when evaluating FBN1 variants. At present, the UMD-FBN1 database seems to be the biggest and best curated; therefore, it is the most comprehensive database. However, the need for better genotype-phenotype curated databases is evident, and we hereby present such a database.Genet Med advance online publication 01 December 2016.