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Takayasu arteritis is a rare, chronic, and large-vessel vasculitis involving the aorta and its branches in a complex autoimmune reaction. Takayasu arteritis sometimes complicates aortic regurgitation and chronic kidney disease, but rarely accompanies nephrotic syndrome. We had a patient with Takayasu arteritis and concomitant aortic regurgitation. She had nephrotic syndrome that was refractory to immunosuppressive therapy but was promptly improved after surgical aortic valve replacement. In her kidney biopsy, glomeruli had mild mesangial proliferative changes without immune complex deposition. Her proteinuria remained negative until the recurrence of aortic regurgitation due to perivalvular leakage. Seventeen years after the surgery, she died suddenly. In her kidney autopsy, the arteriolar showed severe hyalinosis and the glomerulus showed mesangial proliferative changes with segmental mesangiolysis. Severe aortic regurgitation may have altered renal hemodynamics and caused glomerular lesions, resulting in nephrotic syndrome. We should be aware of the rare but critical comorbidity of nephrotic syndrome in patients with Takayasu arteritis and concomitant aortic regurgitation., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach., (© 2024. The Author(s).)

Objective: Aortic valvuloplasty frequency has significantly increased over the past 15 years. Surgical repair varies in complexity depending on valvular lesions. Our aim is to report results on the whole spectrum of aortic valvuloplasty techniques., Methods: All children who consecutively underwent aortic valvuloplasty for aortic stenosis and/or aortic insufficiency between January 2006 and December 2020 at Necker Sick Children's Hospital (Paris, France) were included in a retrospective cohort study. Aortic valvuloplasty techniques were classified into 3 difficulty levels: (1) simple repair, corresponding to commissurotomy and/or shaving in aortic stenosis (AS) in neonates (group 1) and children >1 month (group 2); (2) intermediate-complexity repair, corresponding to commissuroplasty, leaflet resuspension, and fenestration closure in aortic insufficiency (leaflet prolapse in connective tissue disease, isolated leaflet prolapse and Laubry-Pezzi groups); and (3) complex repair requiring a pericardial patch to restore a functional aortic valve in mixed aortic valve disease (bicuspidization with neocommissure and cusp extension groups)., Results: During the study period, 324 children underwent aortic valvuloplasty. Survival and freedom from aortic valve reintervention at 10 years were, respectively, 86.1% and 50.9% in neonates with AS, 95.2% and 71.7% in children >1 month with AS, 93.8% and 79.5% in leaflet prolapse in connective tissue disease, 97.7% and 91.9% in isolated leaflet prolapse, 100% and 88% in those with Laubry-Pezzi syndrome, 97.4% and 84.8% in bicuspidization with neocommissure, and 100% and 54.2% in the cusp extension., Conclusions: Durability of aortic valvuloplasty techniques is satisfactory and offers the possibility to delay the Ross procedure, regardless of the lesion's complexity., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: This study examined the characteristics and outcomes of surgical aortic valve replacement (SAVR) both isolated and in combination with other cardiac surgery in Malaysia from 2015 to 2021., Methods: This was a retrospective study of 1346 patients analyzed on the basis of medical records, echocardiograms and surgical reports. The overall sample was both considered as a whole and divided into aortic stenosis (AS)/aortic regurgitation (AR)-predominant and similar-severity subgroups., Results: The most common diagnosis was severe AS (34.6%), with the 3 most common etiologies being bicuspid valve degeneration (45.3%), trileaflet valve degeneration (36.3%) and rheumatic valve disease (12.2%). The second most common diagnosis was severe AR (25.5%), with the most common etiologies being root dilatation (21.0%), infective endocarditis (IE) (16.6%) and fused prolapse (12.2%). Rheumatic valve disease was the most common mixed disease. A total of 54.5% had AS-predominant pathology (3 most common etiologies: bicuspid valve degeneration valve, degenerative trileaflet valve and rheumatic valve disease), 36.9% had AR-predominant pathology (top etiologies: root dilatation, rheumatic valve disease and IE), and 8.6% had similar severity of AS and AR. Overall, 62.9% of patients had trileaflet valve morphology, 33.3% bicuspid, 0.6% unicuspid and 0.3% quadricuspid. For AS, the majority were high-gradient severe AS (49.9%), followed by normal-flow low-gradient (LG) severe AS (10.0%), paradoxical low-flow (LF)-LG severe AS (6.4%) and classical LF-LG severe AS (6.1%). The overall in-hospital and total 1-year mortality rates were 6.4% and 14.8%, respectively. Pure severe AS had the highest mortality. For AS-predominant pathology, the etiology with the highest mortality was trileaflet valve degeneration; for AR-predominant pathology, it was dissection. The overall survival probability at 5 years was 79.5% in all patients, 75.7% in the AS-predominant subgroup, 83.3% in the AR-predominant subgroup, and 87.3% in the similar-severity subgroup., Conclusions: The 3 most common causes of AS- predominant patients undergoing SAVR is bicuspid valve degeneration, degenerative trileaflet valve and rheumatic and for AR-predominant is root dilatation, rheumatic and IE. Rheumatic valve disease is an important etiology in our SAVR patients especially in mixed aortic valve disease. Study registration IJNREC/562/2022., (© 2023. The Author(s).)

Purpose of Review: The evaluation of aortic regurgitation (AR) has advanced from physical examination and angiography towards evidence based non-invasive quantitative methods, primarily with echocardiography and more recently with cardiac magnetic resonance (CMR). This review highlights the guidelines and recent evidence in the diagnosis and management of AR; and outlines future areas of research., Recent Findings: Contemporary large cohorts of AR patients studied with echocardiography and CMR suggest that the left ventricular remodeling and systolic function triggers for intervention may be lower than previously recommended in the guidelines and emphasize the importance of LV volumes in risk stratification. Important gaps of knowledge in the quantitation of AR severity and patient risk stratification were fulfilled recently. Potential thresholds for intervention using ventricular volumes and CMR quantitative findings were recently described. The criteria for what constitutes hemodynamically significant AR and the optimal timing of intervention AR deserve further study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The study aim was to evaluate long-term results after anatomic restoration of the aortic root., Methods: During an 18-year period, a total of 669 patients underwent valve-sparing root repair (aneurysm 554, dissection 115) using selective sinus replacement. None/trivial, mild, moderate, and severe (grades 3+ and 4+) insufficiency were present in 57, 146, 204, and 262 patients, respectively., Results: The anatomic repair was adjusted to the existing aortic annulus diameter, which was 27.0 ± 3.0 mm on average. Replacement of 1, 2, or 3 sinuses of Valsalva was performed in 209, 234, and 226 patients, respectively. Altogether, 454 additional procedures on the cusps were performed, mostly as cusp patch plasty with pericardium (210). Thirty-day mortality was 0.6%. The mean follow-up duration was 7.1 ± 4.1 years (range, 0.01-19.1 years). The estimated freedom from relevant aortic insufficiency grade 3+ or greater (15 events) was 98% ± 1%, 97% ± 1%, and 94% ± 3% at 5, 10, and 15 years, respectively. On echocardiogram, no patient revealed a considerable change of the form or size of the repaired root, which was confirmed radiologically in 160 patients who received computed tomography angiography for any reason. Multivariate logistic regression analysis identified cusp prolapse/pseudo-prolapse as the only independent risk factor for the development of recurrent insufficiency grade 2+ or greater (41 occurrences), with a hazard ratio of 3.258 (95% confidence interval, 1.658-6.403; P = .001). An association between aortic annulus size and functional results could not be demonstrated., Conclusions: Patient-tailored root repair using isolated sinus replacement offers excellent functional long-term results regardless of underlying root pathology or annulus size. Aortic cusp pathology was decisive for long-term valve function., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Bicuspid aortic valve (BAV) is the most common congenital cardiac defect in the adult population, with a prevalence of 0.5%-2%. It is well recognized that aortic stenosis (AS), aortic regurgitation (AR) and aertopathy may develop by the fifth or sixth decade of life. There is a paucity of autopsy studies evaluating the hearts of subjects with BAV. The aim of this study is to ascertain the role of BAV in cases of sudden cardiac death., Methods: A database of 6325 whole hearts referred to a specialist cardiac pathology center between 2004 and 2021 was reviewed to identify a subgroup of 91 subjects with a BAV reported. All cases had a negative full body autopsy and toxicology before being referred and subsequently underwent detailed cardiac evaluation including histological analysis by expert cardiac pathologists., Results: The mean age of death was 37 ± 16 years (84% male). Death was attributed to aortic valve or aortic disease in 57% (n = 52) of cases; AS 30% (n = 27), endocarditis 11% (n = 10), aortic dissection (AD) 9% (n = 8) and AR 8% (n = 7). In the remaining 43% of cases, BAV was an incidental finding., Conclusion: The majority of deaths in young individuals with BAV were attributed to complications related to the aortic valve or aorta indicating that BAV is not a benign condition. When a BAV is identified, individuals should be appropriately follow-up with imaging to inform the optimal timing of intervention before a complication develops that may predispose the individual to a premature death., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS., Methods and Results: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033)., Conclusion: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purposes: A retrospective analysis was performed to compare the pathological findings and aortic root Z-score in patients with and without connective tissue disease (CTD)., Methods: Twenty-two patients {47.5 [15-85] years old, 18 males} underwent surgery for aortic root dilatation without aortic dissection: 10 {40 [16-59] years old} with CTD and 12 {57.5 [15-85] years old} without CTD (non-CTD; p = 0.049). Systemic hypertension (p = 0.043) and the degree of preoperative aortic regurgitation (p = 0.017) were higher in the non-CTD patients than in the CTD patients., Results: The diameters of the sinotubular junction (STJ) (p = 0.048) and ascending aorta (Asc.Ao.) (p = 0.020) and the Z-scores of the STJ (p = 0.027) and Asc.Ao. (p = 0.009) were significantly higher in the non-CTD patients than in the CTD patients. The degree of translamellar mucoid extracellular matrix accumulation (T-MEMA) of the Asc.Ao. was significantly higher in the non-CTD patients than in the CTD patients (p = 0.037) and was significantly correlated with the Z-scores of the aorta (R = 0.746, p < 0.01 in the sinus of Valsalva and R = 0.382, p = 0.031 in the Asc.Ao.), although there was no significant correlation between the diameter of the STJ and that of Asc.Ao., Conclusions: In non-CTD patients, not only the aortic root but also Asc.Ao. tended to dilate with age, and a significant correlation between the Z-scores of the aorta root and the Asc.Ao. and the degrees of T-MEMA was observed., (© 2021. Springer Nature Singapore Pte Ltd.)

Objective: The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation., Methods: Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair., Results: The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively., Conclusions: An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease., Methods: A total of 131 patients referred for aortic valve replacement were grouped by valve dysfunction (aortic stenosis vs aortic regurgitation) and valve morphology (bicuspid vs tricuspid). On the basis of magnetic resonance imaging, aortic tissue from outer and inner curvature was collected for gene expression and histologic analysis. To identify differences in aortic remodeling, age- and sex-adjusted data for inflammation (CCL2, VCAM1, inflammation and atherosclerosis) and medial degeneration (COL1A1, ELN, fibrosis, elastin fragmentation, and cystic medial necrosis) were compared., Results: First, we compared all patients with aortic regurgitation (n = 64) and patients with aortic stenosis (n = 67). In patients with aortic regurgitation, COL1A1 expression and all histologic markers were significantly increased. With respect to aortic diameter, all subsequent analyses were refined by considering only individuals with aortic diameter 40 mm or greater. Second, patients with bicuspid aortic valve were compared, resulting in a similar aortic diameter. Although patients with aortic regurgitation were younger, no differences were found in gene expression or histologic level. Third, valve morphology was compared in patients with aortic regurgitation. Although aortic diameter was similar, patients with regurgitant bicuspid aortic valve were younger than patients with regurgitant tricuspid aortic valve. Inflammatory markers were similar, whereas markers for medial degeneration were increased in patients with regurgitant tricuspid aortic valve., Conclusions: Our results indicate that the proximal aorta in patients with aortic regurgitation showed an increased inflammation and medial degeneration compared with patients with aortic stenosis. Refining both groups by valve morphology, in patients with bicuspid aortic valve, no difference except age was detected between aortic regurgitation and aortic stenosis. In patients with aortic regurgitation, tricuspid aortic valve revealed increased markers for medial degeneration but no differences regarding inflammatory markers., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Abstract: Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro.

The differences in aortic root geometry associated with various valve-sparing root replacement (VSRR) techniques have not fully been understood. We evaluated the root configuration of current VSRR techniques by developing in vitro test apparatus. Six fresh porcine hearts were used for each model. The aortic root remodeling control group involved replacement of the ascending aorta with diameter reduction of sino-tubular junction (STJ) (C1). The aortic valve reimplantation control group involved replacement of the ascending aorta alone (C2). VSRR included remodeling without (RM) or with annuloplasty (RM + A) and reimplantation with a tube (RI) or a handmade neo-Valsalva graft (RI + V). The root geometry of each model in response to closing hydraulic pressures of 80 and 120 mmHg was investigated using echocardiography. Among the VSRR models, RM yielded the largest aorto-ventricular junction (AVJ), which was similar to those in non-VSRR models [mean AVJ diameter (mm) at 80 mmHg; RM = 25.1 ± 1.5, RM + A = 20.9 ± 0.7, RI = 20.7 ± 0.9, RI + V = 20.8 ± 0.4]. RI + V yielded the largest Valsalva size and largest ratio of Valsalva/AVJ, which was similar to the control group [mean Valsalva diameter (mm) at 80 mmHg; RM = 28.4 ± 1.4, RM + A = 25.8 ± 1.3, RI = 23.6 ± 1.0, RI + V = 30.5 ± 0.8, ratio of Valsalva/AVJ at 80 mmHg; RM = 1.14 ± 0.06, RM + A = 1.24 ± 0.06, RI = 1.15 ± 0.06, RI + V = 1.47 ± 0.05]. The STJ diameter at 80 mmHg was numerically smaller with RM + A (22.4 ± 1.2 mm) than with RM (24.8 ± 2.3 mm, p = 0.11). There were no significant differences in AVJ, Valsalva, or STJ distensibility or ellipticity between procedures. Current modifications, including annuloplasty for remodeling or reimplantation in the setting of neo-Valsalva graft, yield near-physiological root geometries.

Purposes: To perform successful aortic valve plasty (AVP) and valve-sparing root replacement (VSRR), a sufficient understanding of the aortic root and cusp geometry is required. Several key parameters of the aortic root and cusp geometry were, therefore, measured intraoperatively., Methods: Forty-nine patients (63.1 ± 16.6 y.o., 40 males) were measured during the surgeries. The patients were divided into 3 groups; including patients with no or mild aortic valve regurgitation (AR) (n = 13), moderate AR (n = 18), and severe AR (n = 18)., Results: There were no significant differences in the body surface area (1.72 ± 0.19 m 2 ) among the 3 groups (p = 0.858). The effective height (EH) and geometric height (GH) of right coronary cusp were smaller than those of the others (EH: p = 0.068, GH: p < 0.01). The insertion line length (ILL) and free margin length (FML) of each leaflet tended to be significantly longer according to the AR grade(ILL: p < 0.01, FML: p < 0.01). The FML/AVJ ratios were significantly different (p < 0.01). The FML/ILL ratios were constant with the ratio of 0.88 ± 0.1(p = 0.624)., Conclusions: Although the ILL and FML tended to increase with the AR grade, the FML/ILL ratio remained constant. For successful AVP and VSRR, adequately maintaining the FML/ILL ratio is necessary to prevent remarkable cusp prolapse while also preserving its favorable cusp motion.

Objective: The probability of aortic complications in patients with bicuspid aortic valve is higher in association with aortic regurgitation (AR) compared with aortic stenosis (AS) or normally functioning valves. The objective of this study was to determine whether this is related to the specific characteristics of aneurysmatic dilatation that includes AR or whether AR itself has a negative impact on the aortic wall, independent of aneurysmatic dilatation. Approach and Results: Nondilated aortic specimens were harvested intraoperatively from individuals with tricuspid aortic valves and either AS (n=10) or AR (n=16). For controls, nondilated aortas were harvested during autopsies from individuals with tricuspid aortic valves and no evidence of aortic valve disease (n=10). Histological and immunohistochemical analyses revealed that compared with control aortas, overall medial degeneration was more severe in AR-aortas ( P =0.005) but not AS-aortas ( P =0.23). This pathological remodeling included mucoid extracellular matrix accumulation ( P =0.005), elastin loss ( P =0.003), elastin fragmentation ( P =0.008), and decreased expression of fibrillin ( P =0.003) and collagen ( P =0.008). Furthermore, eNOS (endothelial nitric oxide synthase) expression was decreased in the intima ( P =0.0008) and in vasa vasorum ( P =0.004) of AR-aortas but not AS-aortas (all P >0.05). Likewise, subendothelial apoptosis was increased in AR-aortas ( P =0.03) but not AS-aortas ( P =0.50)., Conclusions: AR has a negative effect on the nondilated ascending aortic wall. Accordingly, our results support the need for more detailed studies of the aortic wall in relation to aortic valve disease and may ultimately lead to more aggressive clinical monitoring and/or surgical criteria for patients with relevant AR. Graphic Abstract: A graphic abstract is available for this article.

Background: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1-0.2‰. The causative variant of FNB1 gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis., Case Presentation: The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient., Conclusions: In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.

Background: Aortic valve neocuspidization (AVNeo) (Ozaki procedure) has excellent midterm results in adults. Outcomes in patients with a small native aortic annulus are unknown. We report early outcomes in young patients with small native aortic valve annuli., Methods: Retrospective data of patients undergoing AVNeo between 2015 and 2019 were reviewed. Patients with native aortic annulus less than 21 mm undergoing 3-leaflet AVNeo were included., Results: A total of 51 patients were identified (median age 7.9 years; median weight 21 kg), and 80% patients were less than or equal to 12 years age. Preoperative indication was aortic regurgitation (AR) (n = 23), aortic stenosis (AS) (n = 22), or mixed AS and AR (n = 6). Baseline anatomy was quadricuspid (n = 1), tricuspid (n = 23), bicuspid (n = 15), or unicuspid (n = 12) valve. Preoperative peak gradient for AS and mixed AS and AR patients was 55.36 mm Hg. Median native annulus diameter was 17 mm; sinus and annular enlargements were required in 22 patients and 9 patients, respectively. Median intensive care unit and hospital length of stay were 2.0 days and 7.2 days, respectively. There were no reinterventions, and there was 1 hospital mortality unrelated to aortic valve. At discharge, 94% of patients had less than or equal to mild AR, and the median peak gradient was 18 mm Hg. At mean follow-up of 11.9 months, 80% and 82% of patients had less than moderate AR and AS, respectively. Three patients required surgical reintervention. In annular enlargement patients, mean annulus Z score remained greater than 0 at follow-up., Conclusions: The Ozaki procedure has acceptable short-term results in young patients with small aortic annuli. A larger aortic annulus can be achieved with surgical annular enlargement. Long-term follow-up is necessary to determine late valve function and potential continued annular growth., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Inflammatory aortic diseases are broadly classified into three categories according to the degree of inflammation: atherosclerosis, atherosclerosis with excessive inflammation, and aortitis/periaortitis. This paper presents a case of a 39-year old man with aneurysmal dilatation of thoracic aorta and aortic valve insufficiency. The aortic wall showed thickening and wrinkled "tree bark" appearance as well as apparent scarring of the intima. Histological examination revealed intimal hyperplasia, a granulomatous/giant cell pattern in the inner tunica media, a few epithelioid macrophages, abundant chronic lymphoplasmacytic and histiocytic inflammation and discrete fibrinoid necrosis. The histological findings were indicative of Horton's disease, but no typical clinical features were present. The case illustrates the difficulties involved in diagnosing inflammatory aortic diseases where it may be challenging to arrive at a specific diagnosis despite the knowledge of medical history, and available macroscopic and histological findings.

Herein, we describe a rare case of Corynebacterium jeikeium endocarditis that silently progressed in a 65-year-old man undergoing hemodialysis. Because routine monthly blood examination revealed high C-reactive protein levels, blood cultures were collected, although he had no symptom and was afebrile. After 2 days, a Gram-positive rod was detected in one set of the blood culture. Furthermore, transthoracic echocardiography revealed new aortic regurgitation (AR) and vegetations, and, therefore, infective endocarditis was suspected. Transesophageal echocardiography showed vegetations with a maximum diameter of 8 mm on his aortic valve, with some valve destruction. C. jeikeium was identified in three sets of blood cultures. Administration of daptomycin was started because he had vancomycin allergy. Judging from the high risk of embolization due to vegetations, emergency aortic valve replacement was performed on the second day. C. jeikeium was detected in a resected cardiac valve specimen and blood. This case emphasizes that physicians should always consider the possibility of infective endocarditis even in hemodialysis patients without any symptoms.

Background: Interstitial deletions within the long arm of chromosome 2, involving the 2q31q33 region, are rare but are known to be associated with delays in development, behavioral problems, facial dysmorphism and various hand/foot anomalies., Case Presentation: Here, we describe a case with an interstitial 2q31.3.q32.2 deletion, presenting the previously described phenotype, exhibiting fibromyxoid degeneration of the aortic valve in addition to previously described clinical features., Conclusion: Interstitial deletion in chromosome 2q31.2q32.3 might be associated to a fibromyxoid degeneration of valvular leaflets generating regurgitation. Patients diagnosed with this mutation may require investigation to rule out a valvular disease.

Objective: To identify the preoperative cardiac computed tomography (CT) factors influencing postoperative recurrent aortic regurgitation (AR) in patients who underwent aortic valve repair with the re-implantation technique (David operation) due to AR., Materials and Methods: A total of 117 patients (age, 49.4 ± 15.6 years; 83 males) who underwent the David operation for AR were included in this retrospective study. Aortic root profiles including the aortic regurgitant orifice area (ARO) and the aortic cusp asymmetry ratio of the areas (ASR area ), which is defined as the maximum/minimum areas among the three cusp areas at the level of the commissures, were measured on preoperative cardiac CT scans. Clinical and CT findings were compared between a group with recurrent AR grade < 3 (no, trivial, or mild AR) and recurrent ≥ 3 + AR. To determine the optimal cut-off values of ASR and ARO, the receiver operating characteristic (ROC) curve was used. Cox regression analysis was used for the analysis of the factors affecting recurrent 3 + AR., Results: Postoperatively, recurrent 3 + AR developed in 17 (14.5%) patients and occurred within a median of 268 days (interquartile range: 78-582 days). The cut-off ARO value for discriminating the patients with recurrent 3 + AR was > 24 mm² (sensitivity, 76.5%; specificity 64.8%), and the area under the ROC curve (AUC) was 0.72. For ASR area , the cut-off value was > 1.58 (sensitivity, 76.5%; specificity, 58.0%) and the AUC was 0.64. Multivariable Cox regression showed that ARO > 24 mm² (hazard ratio = 3.79, p = 0.020) was a potential independent parameter for recurrent 3 + AR. ROC for the linear regression model showed that the AUC for both ARO and ASR area was 0.73 (95% confidence interval, 0.64-0.81, p < 0.001)., Conclusion: ARO and ASR area detected on preoperative cardiac CT would be potentially helpful for identifying AR patients who may benefit from the David operation., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

We describe the case of a 75-year-old male with pyoderma gangrenosum (PG) who had severe aortic insufficiency and moderate mitral regurgitation. He had been taking minocycline for 15 years to treat PG. He underwent aortic valve replacement and mitral valve repair. Aortotomy revealed a black discoloration of the aortic valve and sinus of Valsalve., (© 2019 Wiley Periodicals, Inc.)

Background: Dilated left ventricle occurs in chronic aortic and mitral regurgitations. We describe the early outcome of mitral and aortic valve replacement for patients with severely dilated left ventricle in different surgical interventions., Methods: From March 2014 to December 2018, 620 patients with left ventricular end-diastolic diameter (LVEDD) of ≥ 70 mm underwent valve replacement procedures in 8 cardiac surgery centers in Egypt. One hundred ninety four cases (31.3%) underwent aortic valve replacement, 173 cases (27.9%) underwent mitral valve replacement, 123 cases (19.9%) underwent double valve replacement, 59 cases (9.5%) underwent double valve replacement with either tricuspid valve repair or replacement, 33 cases (5.3%) underwent mitral valve replacement with either tricuspid valve repair or replacement, 20 cases (3.2%) underwent mitral valve replacement with CABG, 10 cases (1.6%) underwent aortic valve replacement with CABG, while 8 cases (1.3%) underwent aortic valve replacement with ascending aortic aneurysm repair., Results: Four patients (0.6%) developed new postoperative renal failure, which required dialysis. Twenty-nine patients (4.7%) required reoperation for bleeding. One patient (0.2 %) developed sternal dehiscence. Five patients (0.8%) postoperatively developed stroke. Twenty-five patients (4%) died, and the main causes of death were low cardiac output and sepsis with eventual multi-organ failure., Conclusion: Valve replacement in patients with hugely dilated left ventricle are safe operations with satisfactory outcomes even if combined with other procedures, especially with proper preoperative preparation, intraoperative preservation of posterior mitral leaflet, and meticulous postoperative follow up in the surgical ICU.

The neo-aortic insufficiency in patients with hypoplastic left heart syndrome is an important sequela. We assessed the risks of the neo-aortic valve deterioration by the difference of initial palliations: Group I underwent primary Norwood (Nw) with systemic-to-pulmonary artery shunt (SPS), Group II underwent bilateral pulmonary artery banding (bPAB) and subsequent Nw with SPS (bPAB-Nw/SPS), Group III underwent bPAB and subsequent Nw with bidirectional Glenn (BDG) procedure (bPAB-Nw/BDG). The neo-aortic valve z score changes over time did not reach statistical significance in all groups (p = 0.43 for Group I, 0.20 for Group II, and 0.30 for Group III). The degree of neo-aortic valve insufficiency did not change significantly over time during this period except for Group III (p = 0.34 for Group I, 0.20 for Group II, and 0.02 for Group III). On the other hand, dimensions of the neo-aortic annulus and degrees of neo-aortic insufficiency did not differ significantly among the 3 groups at any pre-determined time. The presence or absence of incision into the sino-tubular junction at Nw did not affect the late neo-aortic valve z score or insufficiency. These data indicate that the difference of initial palliative procedures does not affect late neo-aortic valve insufficiency in Nw survivors. Because valve failure may develop in longer follow-up, further observation should be conducted.

Objectives: We sought to investigate cusp size limitations for valve repair in patients with aortic regurgitation (AR)., Methods: Preoperative computed tomography was performed in 105 patients. Cusp geometric height (GH) and annulus size were measured. Mean patient age was 60.7 ± 13.7 years. Mean GH of 3 cusps was used in the analysis. Annulus cusp mismatch was graded using predicted coaptation length. Patients were categorized by mean GH into group S (GH <16 mm; n = 35) or L (GH ≥16 mm; n = 70)., Results: Preoperative mean GH was 17.1 ± 2.3 mm. GH and body height were significantly correlated (r = 0.61). Intraoperative mean GH (18.8 ± 2.2 mm) was larger than preoperative mean GH (P < 0.0001). However, postoperative (17.1 ± 2.0 mm) and preoperative mean GH did not differ. Moderate AR was not present on predischarge echocardiography. Mild AR was observed in 51% and 17% of patients in groups S and L, respectively (P = 0.006). During follow-up, moderate or severe AR was observed in 14% and 10% of patients in groups S and L, respectively (P = 0.74). Two patients in group S required reoperation for a regurgitant valve. Twenty (83%) and 15 (21%) patients in groups S and L, respectively, had severe annulus cusp mismatch before surgery. Annulus cusp mismatch resolved in most patients in group L postoperatively, whereas more than half the patients in group S still had severe mismatch., Conclusions: Small cusp size (GH <16 mm) is not necessarily a contraindication in aortic valve repair. However, most patients in this group had annulus cusp mismatch. Root replacement or secure annulus plication is mandatory to correct annulus cusp mismatch., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Clinical BAV manifestations pertain to faulty aortic valve (AOV) function, the associated aortopathy, and other complications such as endocarditis, thrombosis and thromboembolism. BAV arises during valvulogenesis when 2 of the 3 leaflets/cusps of the AOV are fused together. Ensuing asymmetric BAV morphologies alter downstream ejection jet flow-trajectories. Based on BAV morphologies, ejection-flows exhibit different wall-impingement and scouring patterns in the proximal aorta, with excessive hydrodynamic wall-shear that correlates closely with mural vascular smooth muscle cell and extracellular matrix disruptions, revealing hemodynamic participation in the pathogenesis of BAV-associated aortopathies. Since the embryologic regions implicated in both BAV and aortopathies derive from neural crest cells and second heart field cells, there may exist a common multifactorial/polygenic embryological basis linking the abnormalities. The use of Electronic Health Records - encompassing integrated NGS variant panels and phenotypic data - in clinical studies could speed-up comprehensive understanding of multifactorial genetic-phenotypic and environmental factor interactions. This Survey represents the first in a 2-article pluridisciplinary work. Taken in toto, the series covers hemodynamic/morphomechanical and environmental (milieu intérieur) aspects in Part 1, and molecular, genetic and associated epigenetic aspects in Part 2. Together, Parts 1-2 should serve as a reference-milestone and driver for further pluridisciplinary research and its urgent translations in the clinical setting., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose of Review: This discussion is intended to review the anatomy and pathology of the aortic valve and aortic root region, and to provide a basis for the understanding of and treatment of the important life-threatening diseases that affect the aortic valve., Recent Findings: The most exciting recent finding is that less invasive methods are being developed to treat diseases of the aortic valve. There are no medical cures for aortic valve diseases. Until recently, open-heart surgery was the only effective method of treatment. Now percutaneous approaches to implant bioprosthetic valves into failed native or previously implanted bioprosthetic valves are being developed and utilized. A genetic basis for many of the diseases that affect the aortic valve is being discovered that also should lead to innovative approaches to perhaps prevent these disease. Sequencing of ribosomal RNA is assisting in identifying organisms causing endocarditis, leading to more effective antimicrobial therapy. There is exciting, expanding, therapeutic innovation in the treatment of aortic valve disease.

Background: The anatomy of the aortic valves plays an important role in the progression of aortic valve disease (AVD) and determination of the appropriate treatment strategy. We described and compared AVD phenotypes according to detailed anatomical classifications and assessed the accuracy of imaging diagnostics using surgical diagnosis as the gold standard., Methods and Results: The study enrolled 602 patients (mean age 55.5±12.9 years; 74.1% male) who underwent their first aortic valve replacement surgery between June 2017 and March 2018 at Fuwai Hospital in Beijing, China. Clinical characteristics, histopathological diagnoses, preoperative transthoracic echocardiography (TTE), and other available imaging data were collected retrospectively from medical records. During surgery, 370 patients were diagnosed with a tricuspid aortic valve (TAV), 228 with a bicuspid aortic valve (BAV), and 4 with a quadricuspid aortic valve (QAV). The primary histopathological finding was myxomatous degeneration (48.4%) for those with TAV and fibrocalcification (57.9%) for those with BAV. Nearly all TAV patients (96.2%) had aortic regurgitation, while the majority of BAV patients had aortic stenosis (73.7%); the severity of stenosis and regurgitation varied across the subtypes of BAV. The overall diagnostic accuracy of preoperative TTE for aortic valve anatomy was 85.5%; accuracy was higher for TAV versus BAV (96.8% vs. 68.0%, P<.001)., Conclusions: We identified different phenotypes of AVD among patients with different detailed anatomical classifications. In addition, the diagnostic accuracy of preoperative TTE for BAV was suboptimal, and more attention is needed to ensure an accurate anatomic diagnosis prior to surgical intervention., (Copyright © 2019. Published by Elsevier Inc.)

Background: In aortic root replacement, "preexisting" or "induced" aortic leaflet prolapse is related to advanced aortic root pathology and can indicate valve repair. Efforts should be made to perform root replacement before leaflet prolapse is in its maximum extent., Materials and Methods: Thirty-nine patients with chronic aortic root dilatation and aortic valve regurgitation (AR) underwent a reimplantation procedure. Contrary to 32 of the 39 patients (group A), 7 of the 39 patients (group B) underwent cusp plication for prolapse. For both groups, data related to the diameter at the level of maximal tubular extension, sinotubular junction, sinus of Valsalva, aorto-ventricular junction (AVJ), and aortic annulus were obtained from preoperative computed tomography scans and analyzed comparatively., Results: Group B showed a higher mean AR grade (P = .007), a higher mean diameter at the level of the aortic annulus (P = .038), AVJ (P = .037), and aortic sinus (P <.001) and a higher sinus dilatation index (existing-to-predicted diameter ratio) (P <.001) than group A. The sinus of Valsalva displayed the best predictive value regarding a plicature-indicating prolapse (P <.001; 95% confidence interval [CI]: 0.809-1.013). A diameter >40 mm was accompanied by an odds ratio (OR) of 24.6 (95% CI: 1.29-496.02). During the follow-up period of 29.0 ± 18.4 months (range: 6-62 months), 1 patient (group A) required reoperation 5 years postoperatively for progressive AR., Conclusion: The sinus of Valsalva diameter seems to have the greatest prognostic value for the development of prolapse. Our data suggest that root repair should be considered earlier in time before leaflet prolapse is complete, which most likely occurs when root dilatation becomes an aneurysm., (2019 Forum Multimedia Publishing, LLC)

Autophagy serves as a cell survival mechanism which becomes dysregulated under pathological conditions and aging. Aortic valve thickening and calcification causing left ventricular outflow obstruction is known as calcific aortic valve stenosis (CAVS). CAVS is a chronic and progressive disease which increases in incidence and severity with age. Currently, no medical treatment exists for CAVS, and the role of autophagy in the disease remains largely unexplored. To further understand the role of autophagy in the progression of CAVS, we analyzed expression of key autophagy genes in healthy, thickened, and calcified valve tissue from 55 patients, and compared them with nine patients without significant CAVS, undergoing surgery for aortic regurgitation (AR). This revealed a upregulation in autophagy exclusively in the calcified tissue of CAVS patients. This difference in autophagy between CAVS and AR was explored by LC3 lipidation in valvular interstitial cells (VICs), revealing an upregulation in autophagic flux in CAVS patients. Inhibition of autophagy by bafilomycin-A1 led to a decrease in VIC survival. Finally, treatment of VICs with high phosphate led to an increase in autophagic activity. In conclusion, our data suggests that autophagy is upregulated in the calcified tissue of CAVS, serving as a compensatory and pro-survival mechanism.

Myxoid degeneration of the aortic valve as a cause of acute aortic valve regurgitation in young age is uncommon. We report a 39-year-old African-American man with a history of epilepsy and hypertension who presented with a 1-month history of worsening shortness of breath. He was diagnosed with acute pulmonary oedema. Transoesophageal echocardiogram showed normal ejection fraction but severe aortic valve insufficiency with small masses on the ventricular side of the right and non-coronary cusps, small vegetations cannot be ruled out but other valves were normal. Subsequent cultures were negative for endocarditis. Myocardial positron emission tomography (PET) scan was strongly suggestive of cardiac sarcoidosis. However, this diagnosis was ruled out as well when he underwent aortic valve replacement with bioprosthetic valve as he did not want to take long-term anticoagulation. Histological examination of the aortic valve showed myxoid degeneration. The patient was doing very well 1 year after the surgery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim of the Study: Calcific aortic valve disease (CAVD) is a progressive disease starting from mild valvular sclerosis and progressing to severe aortic stenosis (AS) with calcified valves. The origin of the calcification is proposed to be mesenchymal cells which have differentiated towards an osteoblastic phenotype. Podoplanin is a glycoprotein expressed in the endothelium of lymphatic vessels and in osteoblasts and osteocytes, mesenchymal cells, as well as in many carcinomas and aortic atherosclerotic lesions. In CAVD, its expression has been evaluated only as a marker of the lymphatic vasculature., Materials and Methods: We determined podoplanin expression in human aortic valves in four patient groups: control (C, n=7), aortic regurgitation (AR, n=8), aortic regurgitation and fibrosis (AR + f, n=15) and AS (n=49) by immunohistochemistry and quantitative real-time PCR (RT-PCR)., Results: Immunohistochemically, podoplanin expression was significantly increased in AR + f and AS groups when compared with the control and AR groups and the level of expression positively correlated with the extent of calcification and vascularity. Podoplanin mRNA levels were 1.7-fold higher in the AS group as compared with the control group (P=.05). Podoplanin-positivity was present not only in lymphatic vessel endothelium but also in osteoblasts, osteocytes, chondrocytes, macrophages and extracellular matrix. The majority of the podoplanin-positivity was in spindle cells with a myofibroblastic phenotype, often associated with calcifications. Tricuspid valves had more calcification-associated podoplanin than bi/unicuspid valves (median 1.52 vs 1.16, P<.001)., Conclusions: CAVD is characterized by an increased expression of podoplanin; this is associated with the differentiation of valvular interstitial cells into calcium-producing, myofibroblast-like cells. In addition, tricuspid valves express relatively more podoplanin than bi/unicuspid valves., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Quantitative 3D assessment of the aortic root may improve planning and success of aortic valve (AV)-sparing operations., Aims: To use 3D transesophageal echocardiography (TEE) to assess the effect of chronic aortic dilatation on aortic root shape and aortic regurgitation (AR) severity and to examine the effects of AV-sparing operations., Methods and Results: To determine the changes with chronic aortic dilatation, we studied 48 patients, 23 with aortic dilatation (Group 1 ≤ mild AR, n = 13; Group 2 ≥ moderate AR, n = 10) and 25 Controls. To determine the changes in AV-sparing operations, a subgroup of 15 patients were examined pre- and post surgery. 3D-TEE images were analyzed using multiplanar reconstruction (QLAB, Philips, Philips Medical Systems, Andover, MA, USA) to obtain aortic root areas, diameters, and lengths. We also calculated a novel parameter called total coaptation surface area (TCoapSA), which sums the contact surface area of all the AV cusps. Compared to Controls, Groups 1 and 2 had significantly larger aortic root areas, inter-commissural distances, and cusp heights. Compared to Group 1 and Controls, Group 2 had significantly smaller TCoapSA when adjusted for aortic annular area (P = 0.001) with shorter coaptation height (P < 0.001). In patients undergoing AV-sparing surgery, TCoapSA was significantly larger post surgery (P = 0.001) with greater coaptation height (P < 0.001) and smaller inter-commissural distances (P < 0.001)., Conclusions: The aortic valve is a dynamic structure that remodels in response to aortic dilatation. Successful valve-sparing surgery corrects these changes. Quantitative modeling of the aortic valve and root could potentially improve the repair to the individual patients and modify outcomes., (© 2018 Wiley Periodicals, Inc.)

A quadricuspid aortic valve is an uncommon valve lesion. Its physical manifestations vary, and it may be associated with other cardiac lesions. Echocardiography is the imaging modality of choice, with computerized tomography or cardiac magnetic resonance imaging being utilized as adjunctive imaging modalities in certain cases. Herein, we present a case series of three patients with this valvular lesion treated at our institution, as well as a contemporary review of the literature., (© 2018 Wiley Periodicals, Inc.)

Background: Left ventricular (LV) remodeling due to aortic regurgitation (AR) often leads to maladaptive responses. We assessed the prevalence and clinical implications of LV remodeling considering LV volume, mass, and relative wall thickness at the time of AR diagnosis., Methods and Results: Between 2008 and 2017, 370 consecutive patients (mean age 67.3 ± 16.1 years, 56.5% males), with moderate or severe AR, were retrospectively analyzed. LV geometric patterns and clinical outcomes (cardiovascular death, hospitalization for heart failure, or aortic valve replacement) were evaluated. LV dilatation (LV end-diastolic volume >75 mL/m 2 ) was present in 228 patients (61.6%). Applying the new LV remodeling classification system, 40 (10.8%) patients had normal geometry, 14 (3.8%) concentric remodeling, 43 (11.6%) concentric hypertrophy (LVH), 45 (12.2%) indeterminate LVH, 38 (10.3%) mixed LVH, 93 (25.1%) dilated LVH, 54 (14.6%) eccentric LVH, and 43 (11.6%) eccentric remodeling. During a median follow-up of 3.48 years (25th-75th percentile 0.91-5.57), 97 (26.2%) had the combined endpoint. LV dilation (P < 0.001), LVH (P < 0.001), and LV remodeling patterns were significantly associated with the combined endpoint. After multivariable adjustment for age, EF, aortic stenosis, CAD history, and moderate mitral regurgitation, dilated LVH (HR 7.61, IC 95% 1.82-31.80; P = 0.005) and eccentric LVH (HR 7.91, IC 95% 1.82-34.38; P = 0.006) were associated with adverse outcome compared to eccentric remodeling, that showed the best event-free survival rate., Conclusions: In a contemporary cohort of patients with AR, applying the new LV remodeling classification system, only a minority had normal geometry. Dilated LVH and eccentric LVH showed distinct outcome penalty after adjustment for confounders., (© 2018 Wiley Periodicals, Inc.)

Objectives: The growing experience in aortic valve (AV) repair showed that annular stabilization is a crucial component to achieve stable long-term results after AV repair. Dynamic changes in the AV annulus during the cardiac cycle may have an impact on annuloplasty design., Methods: We retrospectively analysed full cardiac cycle multislice computed tomography data from 58 consecutive patients (mean age 75.9 ± 6.5 years, 36% men) with normally functioning tricuspid AVs (normal AV subgroup). The following computed tomography parameters were measured during systole and diastole: maximum, minimum and mean AV annulus diameter, AV annular area and AV annular perimeter. The AV annular eccentricity index was calculated (%) [(max AV annulus × 100/min AV annulus) - 100] in systole and diastole. Subsequently, multislice computed tomography data from 20 patients with severe aortic regurgitation were analysed [aortic valve regurgitation (AR) subgroup]., Results: In the normal AV subgroup, there was a significant decrease in the mean AV annulus diameter from systole to diastole (i.e. 24.6 ± 2.5 mm vs 23.9 ± 2.4 mm, respectively; P < 0.001), which occurred predominantly in the short annular axis (i.e. 21.2 ± 2.4 mm in systole vs 19.9 ± 2.3 mm in diastole; P < 0.001). The mean AV annular area decreased significantly in diastole (i.e. 467.5 ± 94.5 mm2 in systole vs 444.8 ± 86.1 mm2 in diastole; P = 0.012). The annular eccentricity index increased significantly in diastole (33.0 ± 12.2% in systole vs 41.4 ± 13.5% in diastole; P < 0.001). Furthermore, we found an inverse linear correlation between the mean AV annulus diameter and the annular eccentricity index (r = -0.40, P = 0.034). The diastolic annular eccentricity index was significantly reduced in the AR subgroup (i.e. 41.4 ± 13.5% in the normal AV subgroup vs 33.7 ± 14.8% in the AR cohort; P = 0.035)., Conclusions: The normal AV annulus undergoes important geometric deformation during the cardiac cycle that is significantly reduced in diastole in the AR scenario. A novel AV annuloplasty system should ideally adapt for this marked diastolic annular eccentricity and thereby allow for dynamic aortic root changes during the cardiac cycle.

Objectives: The association between the aortic root diameter and aortic regurgitation in hypertensive and normotensive people is still disputed, and the underlying mechanisms remain to be clearly elucidated. We aimed to investigate the relationship between the aortic root diameter and trivial to mild functional aortic regurgitation in never-treated hypertensive patients with a new diagnosis compared with healthy normotensive participants., Methods: A total of 182 hypertensives and 232 age-matched normotensives were included in the study. Anthropometric and office blood pressure (BP) measurements, echocardiography, and a carotid stiffness assessment were performed in all of the participants. Aortic measures for the annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta were taken in late diastole according to the leading-edge method., Results: The mean age of all participants was 52 years. Hypertensive patients had a significantly higher body surface area, mean arterial pressure, and pulse pressure (P < .0001) than normotensive participants. Annulus and sinotubular junction diameters adjusted for confounders and indexed to the body surface area were significantly higher in normotensives than in hypertensives. The prevalence of functional aortic regurgitation was higher in hypertensives (34.8% versus 15.4%; P < .0001). Among the hypertensives, no difference in aortic diameters was found between patients with or without functional aortic regurgitation, whereas normotensives with functional aortic regurgitation had larger aortic root diameters. Aging and BP among the hypertensives were the main determinants of functional aortic regurgitation., Conclusions: Hypertensive patients had a smaller indexed aortic root diameter than normotensive participants but had a higher prevalence of trivial to mild functional aortic regurgitation. The aging process is the main determinant of functional aortic regurgitation in both groups, but high BP also plays an important role in hypertensives., (© 2018 by the American Institute of Ultrasound in Medicine.)

We report a 52-year-old male patient who had a quadricuspid aortic valve (QAV) associated with aortic regurgitation (AR) and left ventricular hypertrophy (LVH). A new accessory cusp (ACC) with maximum thickness than other cusps was located between right coronary cusp (RCC) and left coronary cusp (LCC). The histopathological features revealed markedly thickened and distorted cusp architecture with fibrosis and/or myxomatous degeneration in both non-coronary cusp (NCC) and ACC. Two equal sizes for larger cusps (RCC and NCC) and two equal sizes for smaller cusps (LCC and ACC) were obtained. This QAV belonged to type C QAV of Hurwitz's classification, but also suggested as a modified type III of Jagannath's classification or a new type V of Nakamura's classification by locating ACC between RCC and LCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials., Methods: A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables., Results: Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3)., Conclusions: Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aortic dissection usually presents as an acute emergency and less commonly presents as chronic dissection. Two-dimensional and transoesophageal echocardiographic features of aortic dissection generally show dissection flap, dilated aorta and aortic regurgitation. We report a very unusual and extremely rare case of a 40-year-old female patient with chronic aortic dissection presenting as functional double aortic valve., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)