National registry insights on genetic aortopathies and thoracic endovascular aortic interventions.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) in patients with genetic aortopathies (GA) is controversial, given concerns of durability. We describe characteristics and outcomes after TEVAR in patients with GA. METHODS: All patients undergoing TEVAR between 2010 and 2023 in the Vascular Quality Iniatitive were identified and categorized as having a GA or not. Demographics, baseline, and procedural characteristics were compared among groups. Multivariable logistic regression was used to evaluate the independent association of GA with postoperative outcomes. Kaplan-Meier methods and multivariable Cox regression analyses were used to evaluate 5-year survival and 2-year reinterventions. RESULTS: Of 19,340 patients, 304 (1.6%) had GA (87% Marfan syndrome, 9% Loeys-Dietz syndrome, and 4% vascular Ehlers-Danlos syndrome). Compared with patients without GA, patients with GA were younger (50 years [interquartile range, 37-72 years] vs 70 years [interquartile range, 61-77 years]), more often presented with acute dissection (28% vs 18%), postdissection aneurysm (48% vs 17%), had a symptomatic presentation (50% vs 39%), and were less likely to have degenerative aneurysms (18% vs 47%) or penetrating aortic ulcer (and intramural hematoma) (3% vs 13%) (all P < .001). Patients with GA were more likely to have prior repair of the ascending aorta/arch (open, 56% vs 11% [P < .001]; endovascular, 5.6% vs 2.1% [P = .017]) or the descending thoracic aorta (open, 12% vs 2% [P = .007]; endovascular, 8.2% vs 3.6% [P = .011]). No significant differences were found in prior abdominal suprarenal repairs; however, patients with GA had more prior open infrarenal repairs (5.3% vs 3.2%), but fewer prior endovascular infrarenal repairs (3.3% vs 5.5%) (all P < .05). After adjusting for demographics, comorbidities, and disease characteristics, patients with GA had similar odds of perioperative mortality (4.6% vs 7.0%; adjusted odds ratio [aOR], 1.1; 95% confidence interval [CI], 0.57-1.9; P = .75), any in-hospital complication (26% vs 23%; aOR, 1.24; 95% CI, 0.92-1.6; P = .14), or in-hospital reintervention (13% vs 8.3%; aOR, 1.25; 95% CI, 0.84-1.80; P = .25) compared with patients without GA. However, patients with GA had a higher likelihood of postoperative vasopressors (33% vs 27%; aOR, 1.44; 95% CI, 1.1-1.9; P = .006) and transfusion (25% vs 23%; aOR, 1.39; 95% CI, 1.03-1.9; P = .006). The 2-year reintervention rates were higher in patients with GA (25% vs 13%; adjusted hazard ratio, 1.99; 95% CI, 1.4-2.9; P < .001), but 5-year survival was similar (81% vs 74%; adjusted hazard ratio, 1.02; 95% CI, 0.70-1.50; P = .1). CONCLUSIONS: TEVAR for patients with GA seemed to be safe initially, with similar odds for in-hospital complications, in-hospital reinterventions, and perioperative mortality, as well as similar hazards for 5-year mortality compared with patients without GA. However, patients with GA had higher 2-year reintervention rates. Future studies should assess long-term durability after TEVAR compared with the recommended open repair to appropriately weigh the risks and benefits of endovascular treatment in patients with GA.

Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK.

Pathogenic variants in several genes involved in the function or regulation of smooth muscle cells (SMC) are known to predispose to congenital heart disease and thoracic aortic aneurysm and dissection (TAAD). Variants in MYLK are primarily known to predispose to TAAD, but a growing body of evidence points toward MYLK also playing an essential role in the regulation of SMC contraction outside the aorta. In this case report, we present a patient with co-occurrence of persistent ductus arteriosus (PDA) and thoracic aortic dissection. Genetic analyses revealed a novel splice acceptor variant (c.3986-1G > A) in MYLK, which segregated with disease in the family. RNA-analyses on fibroblasts showed that the variant induced skipping of exon 24, which resulted in an in-frame deletion of 101 amino acids. These findings suggest that MYLK-associated disease could include a broader phenotypic spectrum than isolated TAAD, including PDA and obstructive pulmonary disease. Genetic analyses could be considered in families with TAAD and PDA or obstructive pulmonary disease.

Longitudinal echocardiography in pediatric patients with hypermobile Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS.

Echogenomics: Echocardiography in Heritable Aortopathies.

PURPOSE OF REVIEW: The aim of this article is to review the current echocardiographic considerations in the diagnosis and monitoring of patients with inherited aortopathies. RECENT FINDINGS: Aortic dilation is a key feature in heritable aortopathies, and dissection is a leading cause of morbidity and mortality. New genetic and histopathologic findings are helpful in better understanding these conditions. Non-invasive imaging modalities, including echocardiogram, computerized tomography, and magnetic resonance imaging, are essential in monitoring these patients, as well as providing new prognostic factors of arterial stiffness that may help with risk stratification in the future. Diagnosis of heritable aortopathies should be considered with identification of aortic root dilation, particularly in children and young adults, or when there is a family history of aortic disease. Recent adult consensus guidelines highlight the importance of underlying genotype and phenotypic features when considering prophylactic surgical intervention. There are currently no consensus pediatric guidelines.

Evaluating Variation in the Cardiac Management of Children with Hereditary Thoracic Aortic Disease in the United States.

Hereditary thoracic aortic diseases (HTAD) such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos syndrome (VEDS) frequently result in complex cardiovascular pathology that can lead to premature death. However, given limited research and lack of detailed pediatric management guidelines, practice in the U.S. is largely guided by personal experience and/or advice from other professionals. A REDCap survey was composed that covered topics including genetic testing, imaging, and medication choice (all in children), among others. After piloting, the survey was distributed via email and advertised on PediHeartNet. Email addresses of providers were obtained through an established aortic research collaborative and a clinic directory offered through The Marfan Foundation. There were 64 survey responses (pediatric cardiologists 66%; geneticists 13%, genetic counselors 6%; the remaining 15% was comprised of a combination of cardiothoracic surgeons, adult cardiologists, adult congenital specialists, combined cardiology and genetics specialist, nurse practitioners, physician assistants, and nurse coordinators). The most supported indication for genetic evaluation in a child with mild aortic root dilation was family history of thoracic aortic dissection (100%), in contrast to mild root dilation with no other HTAD features (39% supported, 45% did not, 15% saying it would depend on other factors). The majority would start medical therapy in MFS at an aortic root z-score of 2, however differences existed regarding medication preferences for initiation (47% angiotensin receptor blockers, 36% beta blockers, 17% would not or cannot prescribe medication/defer medication choice to another provider). Variation existed for cross-sectional imaging indications and modality and for exercise restrictions, although on average respondents were more lenient than the Bethesda guidelines. While there are areas of general agreement in the cardiac management of children with HTAD, there are also several areas of considerable variation. This highlights the need for additional study in these areas with the ultimate goal of creating consensus guidelines.

Strategies for the Surgical Management of Highly Aggressive Williams Syndrome Aortopathy: A Three Case Report.

Severe aortopathy in Williams syndrome can sometimes present with an initial ascending aortic pathology, followed in short order by more distal multilevel obstruction and recurrence requiring reintervention. In this series, an early, comprehensive surgical approach using a combination of various access and perfusion strategies yielded excellent long-term results.

Bicuspid Aortic Valve Function and Aortopathy on Presentation and Progression in Children: Does Sex Difference Have Any Implications?

Bicuspid aortic valve (BAV) is the most common congenital heart defect. It can be accompanied by aortic regurgitation or stenosis with aortopathies. Studies in adults showed a sex difference, but there are limited number of reports in the pediatric population. To evaluate the difference in bicuspid aortic valve morphology and functionality between sexes, and the presence and progression of aortopathies, a retrospective chart review study was performed at a tertiary referral care center in the Midwest. In our study, we analyzed a cohort of 476 pediatric patients diagnosed with BAV who presented between January 2007 and February 2018. During the follow-up period spanning 2 to 10 years, male patients (n = 314, 66%) had larger aortic valve annulus (AVA) and sinus of Valsalva (SOV) at the time of initial presentation with more likelihood for progression. In the subgroup analysis, the larger SOV in males was observed in isolated BAV patients without genetic syndromes or cardiac malformations, and there were no significant differences between both sexes in the ascending aorta dimension, valve functionality, valve morphology, and the need for intervention in any of the studied groups. As such, these findings may alter the follow-up focus and frequency for patients with BAV, particularly before adulthood, and warrant further studies.

Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome.

BACKGROUND: Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. METHODS: Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. RESULTS: Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). CONCLUSION: Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Implications of Bicuspid Aortic Valve Disease and Aortic Stenosis/Insufficiency as Risk Factors for Thoracic Aortic Aneurysm.

Bicuspid Aortic Valves (BAV) are associated with an increased incidence of thoracic aortic aneurysms (TAA). TAA are a common aortic pathology characterized by enlargement of the aortic root and/or ascending aorta, and may become life threatening when left untreated. Typically occurring as the sole pathology in a patient, TAA are largely asymptomatic. However, in some instances, they are accompanied by aortic valve (AV) diseases: either congenital BAV or acquired in the form of Aortic Insufficiency (AI) or aortic stenosis (AS). When TAA are associated with aortic valve disease, determining an accurate and predictable prognosis becomes especially challenging. Patients with AV disease and concomitant TAA lack a widely accepted diagnostic approach, one that integrates our knowledge on aortic valve pathophysiology and encompasses multi-modality imaging approaches. This review summarizes the most recent scientific knowledge regarding the association between AV diseases (BAV, AI, AS) and ascending aortopathies (dilatation, aneurysm, and dissection). We aimed to pinpoint the gaps in monitoring practices and prediction of disease progression in TAA patients with concomitant AV disease. We propose that a morphological and functional analysis of the AV with multi-modality imaging should be included in aortic surveillance programs. This strategy would allow for improved risk stratification of these patients, and possibly new AV phenotypic-specific guidelines with more vigilant surveillance and earlier prophylactic surgery to improve patient outcomes.

Association of the bovine aortic arch and bicuspid aortic valve with thoracic aortic disease.

BACKGROUND: Both bicuspid aortic valve (BAV) and bovine aortic arch (BA) are considered as markers of thoracic aortic disease (TAD). But the association between them is not yet clear. This study aimed to explore the potential association of BAV and BA with TAD. METHODS: The study involved 449 participants who underwent their first aortic valve replacement in Fuwai Hospital from June 2017 to March 2018. All patients underwent multidetector computed tomography and echocardiography before surgery. The clinical characteristics were recorded to analyze the association between BAV, BA, and TAD. The univariate and multivariate logistic regression analyses were applied to identify the risk factors for TAD. RESULTS: BA accounted for 79.8% of the arch variants and was the most common aortic arch branching variant. BAV was present in 52.6% of the patients with BA and 38.1% of the patients with normal arch (NA). Among the 185 patients in the BAV subgroup, 50 had BA and 135 had NA. No significant differences were found in BAV anatomical phenotype, aortopathy phenotype, and valve function between BA and NA. The multivariate analysis showed that the presence of BAV and male sex were the risk predictors of TAD. BA was not a risk factor for TAD in either univariate or multivariate analysis. CONCLUSIONS: The proportion of BAV in patients with BA was significantly higher than that of NA, but the BAV phenotype and aortopathy were not related to BA. BAV was a risk factor for TAD, whereas BA was not associated with TAD.

Thoracic aortic atherosclerosis in patients with a bicuspid aortic valve; a case-control study.

INTRODUCTION: Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients. METHODS: Atherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006-2020), resulting in a total of 128 inclusions. RESULTS: Histopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 - 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 - 1.61); p = 0.014). CONCLUSION: Ascending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm.

Strategies for Complex Reoperative Aortic Arch Reconstruction in Patients With Congenital Heart Disease.

Aortic dilation is common in patients with congenital heart disease including those with a bicuspid aortic valve, connective tissue disease, coarctation of the aorta, and conotruncal defects. In addition, neo-aortic dilation has been described in patients after aortic reconstruction including the Norwood procedure, the arterial switch operation, and the Ross procedure. Although aortic catastrophe is rare in patients with congenital heart disease, common pathologic endpoints in these patients likely manifest with similar aortic tissue behavior. A lifelong care model with similar indications for surveillance and prophylactic repair to other more common aortopathies is therefore warranted. Still, reoperative aortic arch reconstruction in these patients is often a complex and high-risk endeavor, and in all cases, a tailored and adaptable plan ensuring adequate myocardial and cerebral protection with appropriate rescue measures is paramount. A surgical team taking on these challenging cases should possess an armamentarium of open, hybrid, and endovascular techniques which can be individualized to a patient's unique anatomy, surgical history, and concomitant lesions as well as the team's measured outcomes and experience.

Hereditary haemorrhagic telangiectasia and SMAD4 mutation in a patient with complex single ventricle heart disease.

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient's staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

The Importance of Aortic Valve Bicuspid Phenotype in Valvular Evolution in Pediatric Patients: A Case Report and Literature Mini-Review.

Bicuspid aortic valve (BAV) is the most commonly encountered congenital malformation in the pediatric population, associated with aortic leaflet degeneration and aortopathy. However, studies on BAV and its complications in children are limited. We present the case of a 16-year-old with type 1B BAV with a raphe with fusion between the right and non-coronary cusps who exhibited severe aortic stenosis, regurgitation, and progressive dilatation of the ascending aorta. Surgical intervention, including aortic valve and aortic root replacement, was performed due to the patient's deteriorating condition. Histopathological examination revealed degenerative changes and calcifications in the aortic valve and mucoid fibrosis in the ascending aorta. The results are consistent with BAV patients being predisposed to aortic stenosis and regurgitation due to increased mechanical stress and hemodynamic abnormalities. Although more common in adults and a rare complication in pediatric patients, calcification was previously observed concurrently with rapid valve degeneration in our daily practice. Further studies are needed to improve our understanding of the mechanisms underlying BAV-related complications and refine treatment strategies for pediatric patients.

Pregnancy-associated aortopathy and sudden postpartum death.

A 39-year-old woman who had undergone an uncomplicated elective cesarean section for a low-lying placenta collapsed and died the following day. At autopsy, there was dissection of an aneurysmally-dilated thoracic aorta with 400 mls of fluid and clotted blood in the pericardial sac. There were no features of Marfan syndrome or other connective tissue disorders. Histology revealed thinning of the aortic wall with fragmentation of elastic fibers and no inflammation. Vessels elsewhere were normal. This case demonstrates a rare complication of pregnancy that may not present until after delivery with unexpected collapse and sudden death. Predisposing factors include an increased cardiac output, reduction in systemic vascular resistance, an increase in left ventricular muscle mass, and alterations in serum progesterone and estrogen levels which may cause structural changes to the aortic wall. The possibility of syndromic and familial connective tissue disorders should also be considered.

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

BACKGROUND: The limitation of aortic size-based criteria is gradually recognized in the prediction of aortic events especially in bicuspid aortic valve (BAV) cohorts, while most aortic events happen in patients with proximal aortic diameters <50 mm. Circulating microRNAs (miRs) have been addressed as a novel tool to improve risk stratification in patients with different aortopathies. We aimed to elucidate the correlation between peripheral whole blood and aortic tissue miRs in order to prove the potential availability as a biomarker in the clinical routine. METHODS: All patients who received elective aortic valve repair/replacement ± proximal aortic replacement to BAV disease (n = 65, 2013-2018) were prospectively included. The expression of 10 miRs (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-106a, miR-133a, miR-143 and miR-145) was analyzed in the intraoperatively acquired aortic tissue as well as in the peripheral blood before the surgery. RESULTS: We found a significant correlation between circulating miRs in the peripheral blood and aortic tissue levels of miR-21 (r = 0.293, p = 0.02), miR-133a (r = 0.43, p = 0.02), miR-143 (r = 0.68, p < 0.001), and miR-145 (r = 0.68, p < 0.001). Further, the multivariate logistic regression analysis revealed an association between blood and aortic tissue miR-143 levels each other (Odds Ratio [OR] 1.29, 95% Confidence Interval [CI] 1.11-1.67, p = 0.02; OR 1.36, 95% CI 1.19-2.01, p = 0.03, respectively) and a blood/aortic miR-143 level to dilated aorta (OR 3.61, 95% CI 1.62-9.02, p = 0.01; OR 2.92, 95% CI 1.81-7.05, p = 0.02, respectively). CONCLUSIONS: Our study demonstrates a significant correlation between peripheral whole blood and aortic tissue miRs, confirming the hypothesis that circulating miRs may reflect remodeling processes in the proximal aorta in bicuspid aortopathy patients.

Association between pregnancy and long-term cardiac outcomes in individuals with congenital heart disease.

BACKGROUND: As early life interventions for congenital heart disease improve, more patients are living to adulthood and are considering pregnancy. Scoring and classification systems predict the maternal cardiovascular risk of pregnancy in the context of congenital heart disease, but these scoring systems do not assess the potential subsequent risks following pregnancy. Data on the long-term cardiac outcomes after pregnancy are unknown for most lesion types. This limits the ability of healthcare practitioners to thoroughly counsel patients who are considering pregnancy in the setting of congenital heart disease. OBJECTIVE: We aimed to evaluate the association between pregnancy and the subsequent long-term cardiovascular health of individuals with congenital heart disease. STUDY DESIGN: This was a retrospective longitudinal cohort study of individuals identifying as female who were receiving care in two adult congenital heart disease centers from 2014 to 2019. Patient data were abstracted longitudinally from a patient age of 15 years (or from the time of entry into the healthcare system) to the conclusion of the study, death, or exit from the healthcare system. The primary endpoint, a composite adverse cardiac outcome (death, stroke, heart failure, unanticipated cardiac surgery, or a requirement for a catheterized procedure), was compared between parous (at least one pregnancy >20 weeks' gestation) and nulliparous individuals. By accounting for differences in the follow-up, the effect of pregnancy was estimated based on the time to the composite adverse outcome in a proportional hazards regression model adjusted for the World Health Organization class, baseline cardiac medications, and number of previous sternotomies. Participants were also categorized according to their lesion type, including septal defects (ventricular septal defects, atrial septal defects, atrioventricular septal defects, or atrioventricular canal defects), right-sided valvular lesions, left-sided valvular lesions, complex cardiac anomalies, and aortopathies, to evaluate if there is a differential effect of pregnancy on the primary outcome when adjusting for lesion type in a sensitivity analysis. RESULTS: Overall, 711 individuals were eligible for inclusion; 209 were parous and 502 nulliparous. People were classified according to the World Health Organization classification system with 86 (12.3%) being classified as class I, 76 (10.9%) being classified as class II, 272 (38.9%) being classified as class II to III, 155 (22.1%) being classified as class III, and 26 (3.7%) being classified as class IV. Aortic stenosis, bicuspid aortic valve, dilated ascending aorta or aortic root, aortic regurgitation, and pulmonary insufficiency were more common in parous individuals, whereas dextro-transposition of the great arteries, Turner syndrome, hypoplastic right heart, left superior vena cava, and other cardiac diagnoses were more common in nulliparous individuals. In multivariable modeling, pregnancy was associated with the composite adverse cardiac outcome (36.4%% vs 26.1%%; hazard ratio, 1.83; 95% confidence interval, 1.25-2.66). Parous individuals were more likely to have unanticipated cardiac surgery (28.2% vs 18.1%; P=.003). No other individual components of the primary outcome were statistically different between parous and nulliparous individuals in cross-sectional comparisons. The association between pregnancy and the primary outcome was similar in a sensitivity analysis that adjusted for cardiac lesion type (hazard ratio, 1.61; 95% confidence interval, 1.10-2.36). CONCLUSION: Among individuals with congenital heart disease, pregnancy was associated with an increase in subsequent long-term adverse cardiac outcomes. These data may inform counseling of individuals with congenital heart disease who are considering pregnancy.

Gender differences in bicuspid aortic valve Sievers types, valvulopathy, aortopathy, and outcome of aortic valve replacement.

BACKGROUND: The gender difference of the bicuspid aortic valve (BAV) is not well understood. OBJECTIVES: We evaluated the impact of gender on the Sievers types, valvulopathy, aortopathy, and outcomes of aortic valve replacement (AVR) of BAV patients in a cohort of Chinese patients. METHODS: Among 992 BAV patients without aortic dissection nor congenital heart disease, 658 underwent AVR. The demography, Sievers types, valvulopathy, aortopathy, and outcomes of AVR were compared between genders. RESULTS: Aortic regurgitation (AR ≥ 2+) (39.0% vs. 12.8%, p < .001), aortic root dilation only (3.8% vs. .8%, p = .014), and diffuse dilation (25.3% vs. 4.3%, p < .001) were more common in men, while moderate to severe aortic stenosis (AS) (21.3% vs. 45.7%, p < .001) and ascending dilation only (46.2% vs. 61.2%, p < .001) were more common in women. Men were more prone to develop preoperative AR ≥ 2+ (OR = 5.15, p < .001), moderate to severe AS + AR ≥ 2 + (OR = 2.95, p = .001), and Diffuse aortic dilation (OR = 3.91, p < .001). Sievers types did not have a significant effect on valvular dysfunction. Gender didn't predict early adverse events after AVR (n = 90) (HR = 1.21, p = .44), but male gender predicted a left ventricular ejection fraction <50% after AVR (OR = 3.07, p = .03). CONCLUSIONS: In this BAV series of Chinese patients, gender didn't differ significantly in Sievers types of BAV but showed significant differences in valvulopathy, aortopathy, and LV function after AVR. In addition, the male patients developed more severe conditions at a younger age.

Bicuspid Aortic Valves: an Up-to-Date Review on Genetics, Natural History, and Management.

PURPOSE OF REVIEW: Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. It has a wide spectrum of clinical manifestations including aortic regurgitation (AR), aortic stenosis, and an associated aortopathy with a small but increased risk of aortic dissection. This review describes current knowledge of BAV, from anatomy and genetics to a discussion of multifaceted strategies utilized in the management of this unique patient population. This review will also highlight critical knowledge gaps in areas of basic and clinical research to enhance further understanding of this clinical entity. RECENT FINDINGS: The current knowledge regarding pathophysiologic mechanisms, screening, and surveillance guidelines for BAV and the associated aortopathy is discussed. We also discuss current management techniques for aortic valve repair versus replacement, indications for aortic surgery (root or ascending aorta), and the emergence of the Ross procedure as a viable management option not only in children, but also in adolescents and adults. The varied clinical phenotype of the BAV, resulting in its specific complex hemodynamic interactions, renders it an entity which is separate and distinct from the tricuspid aortic valve pathologies. While various aortic histopathologic and protein alterations in BAV patients have been described, it remains unclear if these changes are causal or the result of hemodynamic alterations imposed by sheer stress on the intrinsically dysfunctional BAV. Medical management for patients with BAV with AS, AI, or dilated aortic roots/ascending aortas remains challenging and needs further investigation. More than 50% of patients with BAV will undergo AVR during their lifetime, and more than 25% of patients with BAV undergo aortic surgery performed for dilation of the aortic root or ascending aorta, often concurrently with AVR. The search for the ultimate genetic or epigenetic cause of the different bicuspid phenotypes will ultimately be facilitated by the next-generation sequencing tools that allow for study of large populations at low cost. Improvements in diagnostic and stratification criteria to accurately risk assess BAV patients are critical to this process.