Aortic Valve Malformation Research Articles

Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive Cardiomyopathy in a Patient with Prior Transcatheter Aortic Valve Replacement

A 68-year-old man presented with chest distress recurring for the past 10 years. An echocardiogram demonstrated bicuspid aortic valve malformation with severe aortic stenosis and ventricular septal thickness of 22 mm. The patient underwent successful transcatheter aortic valve replacement (TAVR). Six months later, he complained of worsening dyspnea and chest distress (New York Heart Association Class III) on exertion. Besides a functional normal AV prosthesis, the echocardiography indicated the left ventricular outflow tract obstruction peak gradient of 122 mmHg at rest. Alcohol septal ablation was performed as the patient was unable to tolerate morrow procedure. His symptoms were relieved immediately after ablation, and no major cardiovascular events were observed during the 20-month follow-up. In conclusion, among patients with concomitant hypertrophic obstructive cardiomyopathy and severe aortic valvular stenosis, consideration for TAVR and alcohol septal ablation should only be made for patients who are at high surgical risk or cannot tolerate thoracotomy.

Weakly supervised classification of aortic valve malformations using unlabeled cardiac MRI sequences

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.

Characteristic Morphologies of the Bicuspid Aortic Valve in Patients with Genetic Syndromes

In patients with bicuspid aortic valve (BAV), complications including progressive aortic stenosis and aortic dilatation develop over time. The morphology of cusp fusion is one of the determinants of the type and severity of these complications. We present the association of morphology of cusp fusion in BAV patients with distinctive genetic syndromes. The Mayo Clinic echocardiography database was retrospectively reviewed to identify patients (age≤22years) diagnosed with BAV from 1990 to 2016. Cusp fusion morphology was determined from the echocardiographic studies, while coexisting cardiac defects and genetic syndromes were determined from chart review. A total of 1,037 patients with BAV were identified: 550 (53%) had an isolated BAV, 299 (29%) had BAV and a coexisting congenital heart defect, and 188 (18%) had BAV and a coexisting genetic syndrome or disorder. There were no differences in distribution of morphology across the three groups. However, right-noncoronary (RN) cusp fusion was the predominant morphology associated with Down syndrome (P=.002) and right-left (RL) cusp fusion was the predominant morphology associated with Turner syndrome (P=.02), DiGeorge syndrome (P=.02), and Shone syndrome (P=.0007), when compared with valve morphology in patients with isolated BAV. Isolated BAV patients with RN cusp fusion had larger ascending aorta diameter (P=.001) and higher number of patients with ≥ moderate aortic regurgitation (P=.02), while those with RL cusp fusion had larger sinus of Valsalva diameter (P=.0006). Morphological subtypes of BAV are associated with different genetic syndromes, suggesting distinct perturbations of developmental pathways in aortic valve malformation.

Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective

BackgroundHypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies.ResultsWe examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2–5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2–5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups.ConclusionsOnly the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome.

Genetic basis of aortic valvular disease.

Aortic valve disease is relatively common and encompasses both congenital and acquired forms. Bicuspid aortic valve (BAV) is the most common type of cardiac malformation and predisposes to the development of calcific aortic valve disease (CAVD). Since the description of the link between NOTCH1, BAV and CAVD approximately a decade ago, there have been significant advances in the genetic and molecular understanding of these diseases. Recent work has defined the congenital cardiac phenotypes linked to mutations in NOTCH1, and in addition, novel etiologic genes for BAV have been discovered using new genetic technologies in humans. Furthermore, several mouse models of BAV have been described defining the role of endothelial Notch1 in aortic valve morphogenesis, whereas others have implicated new genes. These murine models along with other cell-based studies have led to molecular insights in the pathogenesis of CAVD. These findings provide important insights into the molecular and genetic basis of aortic valve malformations, including BAV, specifically highlighting the etiologic role of endothelial cells. In addition, numerous investigations in to the mechanisms of CAVD demonstrate the importance of developmental origins and signaling pathways as well as communication between valve endothelial cells and the underlying interstitial cells in valve disease onset and progression.

Developmental Mechanisms of Aortic Valve Malformation and Disease.

Normal aortic valves are composed of valve endothelial cells (VECs) and valve interstitial cells (VICs). VICs are the major cell population and have distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between the VECs and VICs plays critical roles in aortic valve morphogenesis. Disruption of major cell signaling pathways results in aortic valve malformations, including bicuspid aortic valve (BAV). BAV is a common congenital heart valve disease that may lead to calcific aortic valve disease (CAVD), but there is currently no effective medical treatment for this beyond surgical replacement. Mouse and human studies have identified causative gene mutations for BAV and CAVD via disrupted VEC to VIC signaling. Future studies on the developmental signaling mechanisms underlying aortic valve malformations and the pathogenesis of CAVD using genetically modified mouse models and patient-induced pluripotent stem cells may identify new effective therapeutic targets for the disease.

DOMESTIC EXPLANTS BASEKS IN RECONSTRUCTIVE SURGERY OF AORTA AND MAGISTRAL ARTERIES

Purpose. The use of explants in cardiovascular surgery is often accompanied by infectious, thrombotic, hemorrhagic complications and the most severe complication of postoperative period represents the infection of the explants itself, which develops at a frequency of 1.5 to 6 % followed by a mortality rate of 75–100 %. Thrombosis of the explants after surgery occur with a frequency of 6 to 42 %. Materials and methods. From 1996 to 2015, explants of BASEKS were used in 3 600 patients. Implants of BASEKS were used in 75 patients with aortic valve malformation in combination with an aneurysm of the ascending aorta and prosthetic endocarditis and in 1 944 patients with reconstruction of the aorta and arteries. Results. Bacteriological studies have demonstrated a wide range of antimicrobial action of the modifying components covering the explant and patches. The most promising results were obtained for micro-organisms which most commonly caused infections of these explants. All the sample explants had antimicrobial property and the zone of lysis around these explants were maintained for a longer time (up to 30 days or more). The residual anti-microbial explants after surgery were studied in vitro in 5 patients who died from peritonitis, heart, lungs and kidney failure. Explants after sampling were placed on growth media seeded with clinical strains of microorganisms. Within 12–24 hours, zones (15–18 mm) that caused the delay of the growth of microorganisms were formed around the studied fragments, confirming the preservation of the residual antimicrobial activity of the explants after implantation. During the period of follow-up, in 1.9 % of the patients in immediate postoperative period and in 4.1 % of patients in later postoperative period occurred thrombosis of the explants. Surface festering of the postoperative wound was observed in 155 (4.3 %) patients, deep festering – in 51 (1.4 %), 98 (2.7 %) patients succumbed to postoperative complications. Conclusion. The explants and patches of BASEKS which is antimicrobial, thromb-resistant and impermeable, could be widely used in cardiovascular surgery.

Rheumatic Aortic Valve Disease with Mitral Stenosis—A Case Report

Congenitally malformed aortic valves are more susceptible to valve injury due to rheumatic fever, mechanical stress of altered flow patterns, atherosclerotic risk factors and degenerative changes. Rheumatic involvement usually occurs in childhood and it is progressive leading to diffuse thickening and fibrosis at leaflet edges and thus differentiated from other patterns of valve damage. Background of this case report revealed the bicuspid nature of the aortic valve due to rheumatic commissural fusion and analysis of echocardiographic parameters in combined lesions of both aortic and mitral valves with severe LV (left ventricular) dysfunction. Left ventricular (LV) and left atrial (LA) dilations predisposing to the formation of smoke (SEC-spontaneous echo contrast) in LV and LA as a consequence of mitral and aortic valve disease are illustrated by 2D echocardiographic imaging in this 41-year-old male.

Preliminary Evidence for Aortopathy and an X-Linked Parent-of-Origin Effect on Aortic Valve Malformation in a Mouse Model of Turner Syndrome.

Turner syndrome (TS), most frequently caused by X-monosomy (45,X), is characterized in part by cardiovascular abnormalities, including aortopathy and bicuspid aortic valve (BAV). There is a need for animal models that recapitulate the cardiovascular manifestations of TS. Extracellular matrix (ECM) organization and morphometrics of the aortic valve and proximal aorta were examined in adult 39,XO mice (where the parental origin of the single X was paternal (39,XPO) or maternal (39,XMO)) and 40,XX controls. Aortic valve morphology was normal (tricuspid) in all of the 39,XPO and 40,XX mice studied, but abnormal (bicuspid or quadricuspid) in 15% of 39,XMO mice. Smooth muscle cell orientation in the ascending aorta was abnormal in all 39,XPO and 39,XMO mice examined, but smooth muscle actin was decreased in 39,XMO mice only. Aortic dilation was present with reduced penetrance in 39,XO mice. The 39,XO mouse demonstrates aortopathy and an X-linked parent-of-origin effect on aortic valve malformation, and the candidate gene FAM9B is polymorphically expressed in control and diseased human aortic valves. The 39,XO mouse model may be valuable for examining the mechanisms underlying the cardiovascular findings in TS, and suggest there are important genetic modifiers on the X chromosome that modulate risk for nonsyndromic BAV and aortopathy.

Surgical treatment of aortic paravalvular abscess by infective endocarditis

To summarize the clinical features, pathology and surgical treatment experiences in the patients with aortic paravalvular abscess by infective endocarditis. The study consisted of a retrospective analysis of 29 cases with aortic paravalvular abscess by infective endocarditis underwent surgical treatment between January 2001 and June 2013. Among the 29 patients, 22 were male and 7 were female, and the mean age was (37 ± 16) years (range from 11 to 63 years). The primary cardiac disease was congenital aortic valve malformation in 16 patients. There were 15 patients with a history of severe heart failure. Of 29 cases, 8 abscess cavities, 13 pseudoaneurysms and 6 fistulas were found, and complete aortoventricular discontinuity was present in 5 patients with serious infections. Of them, the abscess was above the annulus in 14 patients and below the annulus in 10 patients, and simultaneously involved the annulus above and below in 5 patients. 19 patients were culture positive either positive preoperative blood cultures or positive cultures of surgical specimens, including 9 patients with Staphylococcus infection. The paravalvular defect was repaired by patch in 19 cases, and by local closure in 10 cases. The valvular annulus was reconstructed simultaneously in 16 patients. Aortic valve replacement was performed in 26 patients, and Bentall procedure in 2 patients, including 23 with prosthetic mechanical valve and 5 with biological valve. Of the total 29 patients, 28 patients were recovered, and 1 patient was died of sepsis. During 3 months to 13 years postoperative follow-up (average 4.5 years), one was died of non-cardiac cause, and no patient had recurrent endocarditis and paravalvular leakage. Aortic paravalvular abscess by infective endocarditis is not uncommon, prone to heart failure. According to the different pathological manifestations, the appropriate surgical approach and strategy can achieve satisfactory outcomes.

Abstract 18574: Examination of a Highly Penetrant Mouse Model of Bicuspid Aortic Valve Demonstrates that Endothelial Notch1 is Required for Proper Morphogenesis of the Aortic Valve

Bicuspid aortic valve (BAV) is the most common type of cardiac malformation with an estimated prevalence of 1-2% in the population. BAV results in significant morbidity as it is one of the leading causes of valve stenosis and regurgitation in adults. We previously reported that mutations in the signaling and transcriptional regulator, NOTCH1 , were a cause of BAV in non-syndromic autosomal-dominant human pedigrees. The Notch signaling pathway is critical for multiple cell differentiation processes, and Notch1 is expressed in the developing and adult aortic valve. Recently, we have generated a new highly penetrant mouse model of aortic valve malformations using Notch1 haploinsufficient mice that are backcrossed in a Nos3-null background. Notch1 and Nos3 compound mutant adult mice ( Notch1 +/- ;Nos3 -/- ) display a nearly 100% incidence of BAV. The aortic valves of adult mutant mice are thickened and have associated stenosis and regurgitation. We have also found that by postnatal day 10, compound mutant mice suffer ~50% lethality compared to NOS3 -/- littermates. Here, we have examined Notch1 +/- ;Nos3 -/- embryos at serial timepoints to elucidate the mechanisms underlying BAV. Examination at embryonic day 18.5 (E18.5) demonstrated normal Mendelian ratios and histologic examination revealed thickened, malformed valve leaflets accompanied by other outflow tract abnormalities in NOS3 -/- ;Notch1 -/+ mice, likely contributing to the neonatal lethality. Further investigation at E13.5 and E15.5 indicated that the NOS3 -/- ;Notch1 -/+ aortic valve leaflets were significantly thicker than controls, suggesting that outflow tract cushion formation and early remodeling may be affected. In addition, we have generated mice are null for Nos3 and haploinsufficient for Notch1 in endothelial-derived cells using mice harboring a Notch1 -floxed allele and Tie2-Cre mice. Our preliminary results indicate that NOS3 -/- ; Notch1 fl/+ ;Tie2Cre + mice recapitulate the NOS3 -/- ;Notch1 -/+ cardiac phenotype and suggest that endothelial Notch1 is required for proper development of the aortic valve. Overall our data indicate that loss of endothelial Notch1 results in abnormal remodeling of the outflow tract cushions and contributes to BAV.

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Identification of Reference Genes for Quantitative RT-PCR in Ascending Aortic Aneurysms

Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue.

Natural History of Adults With Congenitally Malformed Aortic Valves (Unicuspid or Bicuspid)

Appreciation of the frequency of the congenitally malformed aortic valve has come about during the last 50 years, a period during which aortic valve replacement became a predictably successful operation. Study of patients at necropsy with either a congenitally unicuspid (1 true commissure) or bicuspid (2 true commissures) valve in whom no aortic valve operation has been performed has not been conducted during these 50 years, to our knowledge. We studied 218 patients at necropsy with congenitally malformed aortic valves: 28 (13%) had a unicuspid valve and 190 (87%), a bicuspid valve. Their ages at death ranged from 21 to 89 years (mean, 55 yr), and 80% were men. Of the 218 adults, the aortic valve functioned normally during life in 54 (25%) and abnormally in 164 (75%): aortic stenosis in 142 (65%), pure aortic regurgitation without superimposed infective endocarditis (IE) in 2 (1%), and IE superimposed on a previously normally functioning aortic valve in 20 (9%). IE occurred in a total of 31 (14%) of the 218 patients: involving a previously normally functioning valve in 20 (65%) and a previously stenotic valve in 11 (35%). Of the 218 patients, at least 141 (65%) died as a consequence of aortic valve disease (124 patients) or ascending aortic tears with or without dissection (17 patients). An estimated 1% of the population, maybe higher in men, has a congenitally malformed aortic valve. Data from this study suggest that about 75% of them will develop a major complication. Conversely, and encouragingly, about 25% will go through life without a complication.

Moderate Aortic Enlargement and Bicuspid Aortic Valve Are Associated With Aortic Dissection in Turner Syndrome

Background— Girls and women with Turner syndrome are at risk for aortic dissection and rupture. However, the size of the aorta and the clinical characteristics among those with Turner syndrome and dissection have received little attention. Methods and Results— We obtained medical records from 20 individuals who voluntarily participated in the International Turner Syndrome Aortic Dissection Registry. Type A dissections occurred in 17 of 20 (85%) cases, and type B occurred in 3 cases of which 1 occurred after coarctation stent placement. Of those with spontaneous aortic dissections, 18 of 19 (95%) had an associated cardiac malformation that included a bicuspid aortic valve. In 1 individual there was no predisposing finding other than the presence of Turner syndrome. Associated pregnancy was documented in 1 of 19 (5%). More than half (13/19, 68%) came to medical attention &gt;24 hours after the onset of symptoms. For those with type A dissections, the mean ascending aortic size index was 2.7±0.6 cm/m 2 (n=9). Conclusions— Aortic dissection in Turner syndrome occurs in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. The absence of aortic valve or other cardiac malformations appears to markedly reduce the risk of aortic dissection However, aortic dissection can occur in Turner syndrome without cardiac malformations or hypertension. Individuals with Turner syndrome who are &gt;18 years of age with an ascending aortic size index &gt;2.5 cm/m 2 should be considered for an aortic operation to prevent aortic dissection.

Parachute mitral valve accompanied by bicuspid aortic valve on three-dimensional transesophageal echocardiography

We report the findings of three-dimensional (3D) transesophageal echocardiography (TEE) in a patient with a parachute mitral valve (MV) accompanied by aortic valve (AV) malformation. The results indicated an enhanced echo in MV anterior leaves, incrassate, and shortened subvalvular chordae tendineae, and posteromedial papillary muscle that had echo reinforcement, calcification, retroposition, and a significant decrease compared with anterolateral papillary muscle. In addition, the anterolateral papillary muscle was huge, with the bilateral papillary muscles fused partly, and the posterior subvalvular chordae tendineae incrassate, shortened, and attached parachute-like to the anterolateral papillary muscle. The MV appeared dome-shaped for the open limit in diastole with an MV area of 1.6cm. Moreover, the left ventricle increased in size and the bicuspid AV was malformed. Continuous wave Doppler angiograph showed that the flow rate increased to 398cm/seconds at the AV orifice area. A 3D form of the MV structure was observed from the left ventricle using 3D-TEE inspection. The anterolateral papillary muscle was fused with its posteromedial homologue. The chordae tendineae was attached to the anterolateral papillary with the parachute-like structure, indicating dome movement.

Incremental Utility of Real Time Three‐Dimensional Tranthoracic Echocardiography in the Assessment of Congenitally Malformed Aortic Valve

To study the feasibility and additional value of real time three-dimensional transthoracic echocardiography (RT3D-TTE) for anatomical and functional assessment of malformed aortic valve (AV) compared to conventional two-dimensional TTE (2D-TTE). Malformed AV was evaluated in 35 patients (mean age 18 ± 9.5 years, 70% male) by both 2D-TTE and RT3D-TTE. The anatomical definition of aortic cusps (number, direction, and commissures) was evaluated by a 3-point visualization score (1: nonvisualized, 2: inadequate, 3: adequate). 2D-TTE and RT3D-TTE measurements included AV area and maximum diameters of both AV annulus and left ventricular outflow tract (LVOT). Adequate visualization of AV cusps was achieved in 86% of patients by RT3D-TTE compared to 63% by 2D-TTE. The mean and median visualization score obtained by RT3D-TTE were higher than that by 2D-TTE. The opening of commissures was detected in (80%) of patients by RT3D-TTE compared to (34%) by 2D-TTE. AV area planimetry could be obtained in 77% of patients by RT3D-TTE compared to 43% by 2D-TTE. RT3D-TTE visualization score of AV cusps and commissures showed better interobserver agreement (Kappa: 0.62 and 0.72, respectively) than 2D-TTE (0.58 and 0.69, respectively). RT3D-TTE and 2D-TTE measurements of AV annulus and LVOT were well correlated (r = 0.85; P < 0.001) but the RT3D-TTE measurements were significantly larger than that obtained by 2D-TTE (2.05 ± 0.7 cm and 2.5 ± 0.86 cm vs 1.94 ± 0.67 cm and 1.98 ± 0.74 cm; P < 0.01). RT3D-TTE is a feasible technique that allows comprehensive quantitative and qualitative assessment of malformed AV.

Aneurysms of the Ascending Aorta

Aneurysms of the ascending aorta present a special challenge to primary care physicians, internists, and cardiac surgeons because they remain asymptomatic until they present with either dissection or rupture. This review article is based on a selective search of the literature. In the elderly, aneurysms of the ascending aorta are mainly caused by atherosclerosis. In younger patients, the most common cause is Marfan syndrome; less commonly, younger patients may have Loeys-Dietz syndrome, non-syndromic familial aortic aneurysms, or aortic valve malformations. Genetic variants predisposing to the development of sporadic aortic aneurysms have recently been identified. The risk of rupture and dissection depends on the aortic diameter: when the diameter exceeds 55 mm, surgery improves the outcome, as the risk of surgical complications is lower than the mortality due to rupture or dissection. A more accurate prognosis can be obtained by normalizing the aortic diameter to the body surface area. For patients with Marfan syndrome or a bicuspid aortic valve, the indications for surgery should be determined on an individual basis, depending on additional risk factors. Randomized treatment trials are lacking. The medical management of aneurysms of the ascending aorta consists of monitoring the size of the aneurysm, controlling blood pressure, and treating any cardiovascular risk factors. Patients with Marfan syndrome benefit from preventive treatment with beta-blockers. Advances in the pathophysiological understanding of aortic aneurysms have led to the testing of new types of treatment, e.g., with AT1 antagonists. With the aid of a risk-based treatment strategy, surgery can be properly timed to prevent dissection, which is usually lethal when it occurs. More research is needed on the pathogenesis of this condition so that better preventive treatments can be developed.

Effect of Coronary Bypass and Valve Structure on Outcome in Isolated Valve Replacement for Aortic Stenosis

Reports differ regarding the effect of concomitant coronary artery bypass grafting (CABG) in patients who undergo aortic valve replacement (AVR) for aortic stenosis (AS), and no reports have described the effect of aortic valve structure in patients who undergo AVR for AS. A total of 871 patients aged 24 to 94 years (mean 70) whose AVR for AS was their first cardiac operation, with or without first concomitant CABG, were included. Patients who underwent mitral valve procedures were excluded. In comparison with the 443 patients (51%) who did not undergo CABG, the 428 (49%) who underwent concomitant CABG were significantly older, were more often male, had lower transvalvular peak systolic pressure gradients and larger valve areas, had lower frequencies of congenitally malformed aortic valves, had lighter valves by weight, had higher frequencies of systemic hypertension, and had longer stays in the hospital after AVR. Early and late (to 10 years) mortality were similar by propensity-adjusted analysis in patients who did and did not undergo concomitant CABG. Congenitally unicuspid or bicuspid valves occurred in approximately 90% of those aged 21 to 50, in nearly 70% in those aged 51 to 70 years, and in just over 30% in those aged 71 to 95 years. Unadjusted and adjusted survival was significantly higher in patients with unicuspid or bicuspid valves compared to those with tricuspid valves. In conclusion, although concomitant CABG had no effect on the adjusted probability of survival, the type of aortic valve (unicuspid or bicuspid vs tricuspid) significantly affected the unadjusted and adjusted probability of survival.

Maladaptive matrix remodeling and regional biomechanical dysfunction in a mouse model of aortic valve disease

Aortic valve disease (AVD) occurs in 2.5% of the general population and often requires surgical intervention. Aortic valve malformation (AVM) underlies the majority of cases, suggesting a developmental etiology. Elastin haploinsufficiency results in complex cardiovascular problems, and 20–45% of patients have AVM and/or AVD. Elastin insufficient (Eln+/−) mice demonstrate AVM and latent AVD due to abnormalities in the valve annulus region. The objective of this study was to examine extracellular matrix (ECM) remodeling and biomechanical properties in regional aortic valve tissue and determine the impact of early AVM on late AVD in the Eln+/− mouse model. Aortic valve ECM composition and remodeling from juvenile, adult, and aged stages were evaluated in Eln+/− mice using histology, ELISA, immunohistochemistry and gelatin zymography. Aortic valve tissue biomechanical properties were determined using micropipette aspiration. Cartilage-like nodules were demonstrated within the valve annulus region at all stages identifying a developmental abnormality preceding AVD. Interestingly, maladaptive ECM remodeling was observed in early AVM without AVD and worsened with late AVD, as evidenced by increased MMP-2 and MMP-9 expression and activity, as well as abnormalities in ADAMTS-mediated versican processing. Cleaved versican was increased in the valve annulus region of aged Eln+/− mice, and this abnormality correlated temporally with adverse alterations in valve tissue biomechanical properties and the manifestation of AVD. These findings identify maladaptive ECM remodeling in functional AVM as an early disease process with a progressive natural history, similar to that seen in human AVD, emphasizing the importance of the annulus region in pathogenesis. Combining molecular and engineering approaches provides complementary mechanistic insights that may be informative in the search for new therapeutic targets and durable valve bioprostheses.