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Background Due to ongoing left ventricular (LV) remodeling and consecutive geometric displacement of both papillary muscles, end-stage heart failure is frequently associated with relevant functional mitral regurgitation (FMR) Type IIIb. Treatment strategies of FMR and their prognostic impact are still controversial. Case summary We present a case of an 80-year-old patient who suffered from recurrent symptoms of congestive heart failure due to dilated cardiomyopathy and concomitant severe FMR. To specifically address severe tethering of both mitral leaflets heart team decision was to perform minimally invasive mitral valve repair (MVR) including a subannular LV remodeling procedure, instead of an interventional edge-to-edge repair (MitraClip® procedure). In addition to mitral valve ring annuloplasty, standardized relocation of both papillary muscles was performed successfully, leading to a complete resolution of mitral leaflet tethering. There were no procedural complications and the patient was discharged with an excellent functional result without residual mitral regurgitation. Furthermore, after 12 and 24 months, he reported an increase of his functional exercise capacity and a remarkable reverse LV remodeling could be demonstrated. Discussion Novel subannular repair techniques, especially the relocation of both papillary muscles, specifically address severe leaflet tethering in FMR and have an obvious potential to improve long-term competence of MVR. Therefore, they could be considered as a viable therapeutic option even in elderly patients presenting with end-stage cardiomyopathy and severe leaflet tenting.

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.

Summary Systolic heart failure is frequently accompanied by a relevant functional mitral valve regurgitation (FMR) which develops as a direct sequela of the ongoing left ventricular remodelling. The severity of mitral regurgitation is further aggravated by progressive left ventricular enlargement causing leaflet tethering and reduced systolic leaflet movement. The prognosis of such patients is obviously limited by an underlying left ventricular disease, and the correction of secondary FMR has been previously suggested as predominantly ‘cosmetic’ surgery in the setting of ongoing cardiomyopathy. Inferior results of an isolated annuloplasty in type IIIb FMR supported the philosophy of malignant course of progressive cardiomyopathy and resulted in increasingly restricted indications for mitral valve surgery for FMR in the guidelines. The lack of a standardized pathophysiological approach to correct type IIIb FMR led to the development of valve replacement strategy and edge-to-edge catheter-based mitral valve procedures, which became the most frequent procedures in the FMR setting in Europe. Modern mitral valve surgery combines the advantages of 3-dimensional endoscopic minimally invasive surgical approach with standardized subannular repair to address the pathophysiological background of type IIIb FMR. The perioperative results have been significantly improved, and there is a growing evidence of improved long-term stability of subannular repair procedures as compared to isolated annuloplasty. This review article aims to present the current state-of-the-art of the modern mitral valve surgery in FMR and provides suggestions for future trials analysing the potential advantages in these patients.

OBJECTIVES We aimed to evaluate the impact of microRNAs to predict the bicuspid aortic valve (BAV)-associated aortopathy. METHODS Sixty-three BAV patients (mean age 47 ± 11 years, 92% men) with root dilatation, who underwent aortic valve ± proximal aortic surgery (mean post-AVR follow-up 10.3 ± 6.9 years) were included. The BAV aortopathy entities were categorized in the 'less dilated' (aortic root

OBJECTIVES Functional mitral regurgitation (FMR) is a sequel of left ventricular (LV) remodelling in heart failure patients. Relocation of both papillary muscles aims to specifically address mitral leaflet tethering to improve long-term durability of modern FMR repair. Nevertheless, the prognostic impact of the underlying cardiomyopathy on the outcome after FMR repair is unknown. METHODS We analysed 84 consecutive heart failure patients with severe FMR, LV ejection fraction 10 mm, who underwent ring annuloplasty and simultaneous bilateral papillary muscles relocation between June 2016 and March 2019. One-year outcome of 54 patients with ischaemic cardiomyopathy (‘ICM group’) was prospectively compared to the remaining 30 patients with dilated cardiomyopathy (‘DCM group’). RESULTS One-year survival was similar in both groups (96% in the ‘ICM group’ vs 97% in the ‘DCM group’; P = 0.93). Furthermore, primary composite outcome (i.e. freedom from death or mitral regurgitation ≥ 2) at 1-year postoperatively was comparable between the study groups (94%in the ‘ICM group’ vs 87% in the ‘DCM group’; P = 0.10). LV end-diastolic diameter 1-year after surgery was significantly reduced, as compared to preoperative values, in the ‘DCM group’ (P = 0.018), but not in the ‘ICM group’ (P = 0.058). Improvement of New York Heart Association functional class and reduction of serum levels of N-terminal pro-B natriuretic peptide at 1 year was comparable in both study groups. CONCLUSIONS Standardized relocation of both papillary muscles to correct FMR resulted in very satisfactory in-hospital and 1-year outcomes, in both ICM and DCM. DCM patients showed similar improvement in heart failure symptoms and LV re-remodelling compared to ICM patients. Subannular repair is developing towards a valid therapeutic option in heart failure patients presenting with severe FMR.

Background The major drawback of isolated annuloplasty in secondary mitral regurgitation (MR) is the reoccurrence of MR. We prospectively compared the results of isolated annuloplasty vs annuloplasty with simultaneous standardized subannular repair. Methods The study comprised 101 patients with secondary type IIIb MR. Of these, 51 underwent annuloplasty plus standardized subannular repair with realignment of both papillary muscles (subannular repair) and 50 underwent isolated annuloplasty. The primary study end point was the reoccurrence of MR >2 at the 1-year follow-up. Secondary end points were survival, freedom from major adverse cardiac events, and residual leaflet tethering. Results Baseline characteristics were comparable in both groups. There was no significant difference in in-hospital mortality (P = .3). Although postrepair MR was comparable between the subannular repair and isolated annuloplasty subgroups, the residual leaflet tethering (tenting area, 127.6 ± 35.8 mm2 vs 166.3 ± 47.3 mm2, P = .02; posterior mitral leaflet angle, 19.2 ± 4.7 degrees vs 24.8 ± 5.2 degrees, P = .001; anterior mitral leaflet angle, 25.4 ± 5.8 degrees vs 34.1 ± 4.0 degrees, P = .001; and tenting height, 5.9 ± 1.4 mm vs 9.2 ± 2.2 mm, P = .001) were significantly increased in the isolated annuloplasty group (P 2 of 98% (50 of 51) for subannular repair vs 86.7% (39 of 45) for isolated annuloplasty (P = .045) and mortality of 0% (0 of 51) for subannular repair vs 10% (5 of 50) for isolated annuloplasty (P = .025). Conclusions In secondary MR with reduced leaflet motion, the combination of annuloplasty and standardized subannular repair is associated with a significantly reduced MR reoccurrence, decreased residual leaflet tenting, and significantly improved 1-year outcome compared with annuloplasty alone.

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.

The ascending aortic dilatation may progress after aortic valve replacement (AVR) in bicuspid aortic valve (BAV) patients. Our aim was to evaluate rheological flow patterns and histological characteristics of the aneurysmal aorta in BAV patients at the time of reoperative aortic surgery. 13 patients (mean age: 42 ± 9 years, 10 (77%) male) with significant progression of proximal aortopathy after isolated AVR surgery for BAV disease (i.e., 16.7 ± 8.1 years post-AVR) were identified by cardiac phase-contrast cine magnetic resonance imaging (MRI) in our hospital. A total of nine patients (69%) underwent redo aortic surgery. Based on the MRI data, the aortic area of the maximal flow-induced stress (jet sample) and the opposite site (control sample) were identified and corresponding samples were collected intraoperatively. Histological sum-score values [i.e. aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3)] were compared between these samples. Mean proximal aortic diameter at MRI follow-up was 55 ± 6 mm (range 47–66mm). Preoperative cardiac MRI demonstrated eccentric systolic flow pattern directed towards right-lateral/right posterior wall of the proximal aorta in 9/13 (69%) patients. Histological sum-score values were significantly higher in the jet sample vs control sample (i.e., 8.3 ± 3.8 vs 5.6 ± 2.4, respectively, p = 0.04). Hemodynamic factors may still be involved in the late progression of bicuspid aortopathy even after isolated AVR surgery for BAV disease.

Objectives Genetic defects associated with bicuspid aortopathy have been infrequently analysed. Our goal was to examine the prevalence of rare genetic variants in patients with a bicuspid aortic valve (BAV) with a root phenotype using next-generation sequencing technology. Methods We investigated a total of 124 patients with BAV with a root dilatation phenotype who underwent aortic valve ± proximal aortic surgery at a single institution (BAV database, n = 812) during a 20-year period (1995-2015). Cross-sectional follow-up revealed 63 (51%) patients who were still alive and willing to participate. Systematic follow-up visits were scheduled from March to December 2015 and included aortic imaging as well as peripheral blood sampling for genetic testing. Next-generation sequencing libraries were prepared using a custom-made HaloPlex HS gene panel and included 20 candidate genes known to be associated with aortopathy and BAV. The primary end-point was the prevalence of genetic defects in our study cohort. Results A total of 63 patients (mean age 46 ± 10 years, 92% men) with BAV root phenotype and mean post-aortic valve replacement follow-up of 10.3 ± 4.9 years were included. Our genetic analysis yielded a wide spectrum of rare, potentially or likely pathogenic variants in 19 (30%) patients, with NOTCH1 variants being the most common ( n = 6). Moreover, deleterious variants were revealed in AXIN1 ( n = 3), NOS3 ( n = 3), ELN ( n = 2), FBN1 ( n = 2) , FN1 ( n = 2) and rarely in other candidate genes. Conclusions Our preliminary study demonstrates a high prevalence and a wide spectrum of rare genetic variants in patients with the BAV root phenotype, indicative of the potentially congenital origin of associated aortopathy in this specific BAV cohort.

Controversy exists regarding the pathogenesis of bicuspid aortic valve (BAV) associated aortopathy. Recent data indicate the potential role of lipid metabolism in the expression of aortopathy.