Three-dimensional transoesophageal echocardiography: how to use and when to use-a clinical consensus statement from the European Association of Cardiovascular Imaging of the European Society of Cardiology.

Three-dimensional transoesophageal echocardiography (3D TOE) has been rapidly developed in the last 15 years. Currently, 3D TOE is particularly useful as an additional imaging modality for the cardiac echocardiographers in the echo-lab, for cardiac interventionalists as a tool to guide complex catheter-based procedures cardiac, for surgeons to plan surgical strategies, and for cardiac anaesthesiologists and/or cardiologists, to assess intra-operative results. The authors of this document believe that acquiring 3D data set should become a 'standard part' of the TOE examination. This document provides (i) a basic understanding of the physic of 3D TOE technology which enables the echocardiographer to obtain new skills necessary to acquire, manipulate, and interpret 3D data sets, (ii) a description of valvular pathologies, and (iii) a description of non-valvular pathologies in which 3D TOE has shown to be a diagnostic tool particularly valuable. This document has a new format: instead of figures randomly positioned through the text, it has been organized in tables which include figures. We believe that this arrangement makes easier the lecture by clinical cardiologists and practising echocardiographers.

Importance of relative binding of bisphenol A and bisphenol S to plasma proteins for predicting their in vivo potencies.

Many studies suggest that the potential impact of bisphenol S (BPS) as an endocrine disruptor is comparable to that of bisphenol A (BPA). However, in vitro-to-in vivo and from animal to human extrapolations require knowledge of the plasma free fraction of the active endocrine compounds. The present study aimed to characterise BPA and BPS binding to plasma proteins both in humans and different animal species. The plasma protein binding of BPA and BPS was assessed by equilibrium dialysis in plasma from adult female mice, rats, monkeys, early and late pregnant women as well as paired cord blood, early and late pregnant sheep and foetal sheep. The fraction of free BPA was independent of plasma concentrations and ranged between 4% and 7% in adults. This fraction was 2 to 3.5 times lower than that of BPS in all species except sheep, ranging from 3% to 20%. Plasma binding of BPA and BPS was not affected by the stage of pregnancy, BPA and BPS free fractions representing about 4% and 9% during early and late human pregnancy, respectively. These fractions were lower than the free fractions of BPA (7%) and BPS (12%) in cord blood. Our results suggest that similarly to BPA, BPS is extensively bound to proteins, mainly albumin. The higher fraction of free BPS compared to BPA may have implications for human exposure assessment since BPS free plasma concentrations are expected to be 2 to 3.5 times higher than that of BPA for similar plasma concentration.

Mapping of the myxomatous mitral valve: The three-dimensional extension of mitral annular disjunction in surgically repaired mitral prolapse.

Objectives: This study aimed to describe the heterogeneous extension of mitral annular disjunction (MAD) and assess the hypotesis that different phenotypes of disjunction are not associated with increased surgical challenges. Background: Mitral regurgitation (MR) is the most common end-stage scenario of degenerative mitral valve disease (DMVD). Few data exist on the three-dimensional extension and geometry of MAD, as well as for its role in valvular dynamic and coaptation. Methods: A total of 85 consecutive subjects, who underwent elective mitral valve repair (MVR) for MMVD at our Institution between November 2019 and October 2021, were studied retrospectively. The extension and geometry of MAD was assessed using the digitally stored volumetric datasets of real-time 3D transesophageal echocardiography (TEE). Annular phenotypes and surgical repair techniques were analyzed. Results: Mitral annular disjunction was diagnosed in 50 out of 85 patients (59%) with Barlow disease (BD). A detailed analysis of MAD extension was conducted on 33 patients. Two pattern of disjunction were identified: a bimodal shape was highlighted in 21 patients, while a more uniform distribution of the disjuncted annulus was observed in 12 patients. The bimodal pattern was characterized by lower disjunction distance (DD) at the 140°-220° arch (3.6 ± 2.2 mm), while a more regular DD was measured in the remaining patients. All patients successfully underwent MVR. Triangular leaflet resection was performed in 58% of the cases, neochordae implantation in 9%, and notably a 27% received an isolated annuloplasty. Conclusion: Rather than a binary feature, MAD should be taken into account in its complex and heterogeneous morphology, where two major phenotypes can be identified. Despite its anatomical complexity, MAD was not associated with an increased surgical challenge; conversely a peculiar subgroup of patient was successfully treated with an isolated annuloplasty.

Bicuspidization of a unicuspid valve using sliding plasty of a rudimentary right coronary cusp.

Unicuspid aortic valve repair relies on the principles of bicuspidization by creating a neo-commissure at 180° from the existing commissure, with pericardial patch interposition. We report a case of a 26-year-old patient with cor triatriatum and a severely regurgitating unicuspid valve. The left atrium membrane was resected. Aortic valve repair was performed creating a neo-commissure using a sliding plasty of the rudimentary right coronary cusp and patch reconstruction of the anterior part of the non-coronary cusp, protected by external subvalvular annuloplasty and hemi-root remodelling. We detail a repair technique of a partial autologous reconstruction approach for bicuspidization.

Grading mitral regurgitation using 4D flow CMR: Comparison to transthoracic echocardiography.

OBJECTIVES: To determine the 4D Flow Cardiac Magnetic Resonance (CMR) thresholds that achieve the best agreement with transthoracic echocardiography (TTE) for grading mitral regurgitation (MR). METHODS: We conducted a single-center prospective study of patients evaluated for chronic primary MR in 2016-2020. MR was evaluated blindly by TTE and 4D Flow CMR, respectively by two cardiologists and two radiologists with decades of experience. MR was graded with both methods as mild, moderate, or severe. 4D Flow CMR measurements included MR regurgitant volume per beat (RV) and mitral anterograde flow per beat (MF). RF was obtained as the ratio RV/MF. Additionally, MF was compared to left ventricular stroke volume (LVSV) by cine-CMR. RESULTS: We included 33 patients in the initial cohort and 33 in the validation cohort. Inter-observer agreement was excellent for 4D Flow CMR ICC = .94 (95% CI, .86-.97, p < 0.0001). Using recommended TTE thresholds (30 ml, 60 ml, 30%, 50%), agreement was moderate for RV and RF. The best agreement between 4D Flow CMR and TTE was obtained with CMR thresholds of 20 and 40 ml for RV (κ = .93; 95% CI, .8-1) and 20% and 37% for RF (κ = .90; 95% CI, .7-.9). In the validation cohort, agreement between TTE and 4D Flow CMR was good with the optimal thresholds (κ = .78; 95% CI, .61-.94). CONCLUSION: We propose CMR thresholds that provide a good agreement between TTE and CMR for grading MR. Further studies are needed to fully validate 4D-Flow CMR accuracy for primary MR quantification.

Aortic valve repair versus mechanical valve replacement for root aneurysm: the CAVIAAR multicentric study.

OBJECTIVES: Despite growing evidence that aortic valve repair improves long-term patient outcomes and quality of life, aortic valves are mostly replaced. We evaluate the effect of aortic valve repair versus replacement in patients with dystrophic aortic root aneurysm up to 4 years. METHODS: The multicentric CAVIAAR (Conservation Aortique Valvulaire dans les Insuffisances Aortiques et les Anévrismes de la Racine aortique) prospective cohort study enrolled 261 patients: 130 underwent standardized aortic valve repair (REPAIR) consisting of remodelling root repair with expansible aortic ring annuloplasty, and 131 received mechanical composite valve and graft replacement (REPLACE). Primary outcome was a composite criterion of mortality, reoperation, thromboembolic or major bleeding events, endocarditis or operating site infections, pacemaker implantation and heart failure, analysed with propensity score-weighted Cox model analysis. Secondary outcomes included major adverse valve-related events and components of primary outcome. RESULTS: The mean age was 56.1 years, and valve was bicuspid in 115 patients (44.7%). Up to 4 years, REPAIR did not significantly differ from REPLACE in terms of primary outcome [Hazard Ratio (HR) 0.66 (0.39; 1.12)] but showed significantly less valve-related deaths (HR 0.09 [0.02; 0.34]) and major bleeding events (HR 0.37 [0.16; 0.85]) without an increased risk of valve-related reoperation (HR 2.10 [0.64; 6.96]). When accounting for the occurrence of multiple events in a single patient, the REPAIR group had half the occurrence of major adverse valve-related events (HR 0.51 [0.31; 0.86]). CONCLUSIONS: Although the primary outcome did not significantly differ between the REPAIR and REPLACE groups, the trend is in favour of REPAIR by a significant reduction of valve-related deaths and major bleeding events. Long-term follow-up beyond 4 years is needed to confirm these findings.

Aortic valve fenestration: respect it or fix it?

OBJECTIVES: We investigated whether aortic valve fenestrations (respected or fixed) represent a factor associated with recurrent aortic insufficiency or reoperation after repair. METHODS: Between 2003 and 2019, patients who underwent aortic valve repair were included. Aortic insufficiency phenotypes were root aneurysm (repair: root remodelling + annuloplasty), ascending aorta aneurysm (repair: tubular aortic replacement + annuloplasty) and isolated regurgitation (repair: single/double annuloplasty). Fenestrations were either respected or fixed according to their features. RESULTS: A total of 618 patients (out of 798 operated on; 77.4%) had their valve repaired, with 167 cases of fenestrations (128 were respected, 39 fixed-32 with a patch, 6 with running suture and 1 with both). After conducting propensity score matching between no-fenestration (n = 167) and fenestration groups (n = 167), respectively, we noted the following: survival [90.3% (n = 7 deaths) vs 95.8% (n = 4)], cumulative incidence of reoperation [6.7% (n = 7) vs 5.2% (n = 4)], aortic insufficiency grade ≥ 3 [6.4% (n = 6) vs 4.4% (n = 4)] and grade ≥ 2 [28.9% (n = 28) vs 37.1% (n = 35)] were similar at 9 years [P = 0.94; median follow-up: 2.2, interquartile range: (0.8, 5.8)], whether fenestration was respected (P = 0.55) or fixed (P = 0.6, at 6 years). Standardization of the surgical approach (consisting of double annuloplasty in isolated regurgitation phenotype and expansible subvalvular annuloplasty with effective height assessment with remodelling repair for root aneurysm phenotype) reduced the risk of reoperation (era before standardization: hazard ratio: 5.4, 95% confidence interval: 1.9-15.7, P = 0.002). CONCLUSIONS: Fenestration, respected or fixed, is not a factor associated with reoperation or recurrence of significant aortic insufficiency after valve repair if the surgical approach is standardized.

Aortic valve repair using pericardial patch standardized with external ring annuloplasty.

OBJECTIVES: This study was undertaken to analyse outcomes of aortic valve repair using additional material and compare the results to those of cusp repair without the use of the pericardial patch. METHODS: All consecutive patients aged over 16 who underwent aortic valve repair with external ring annuloplasty for isolated aortic insufficiency, aortic insufficiency and tubular aortic aneurysm or aortic root aneurysm between May 2003 and November 2019 were included in a cohort study. Data were collected and analysed from the AVIATOR registry (AorticValve repair InternATiOnal Registry). Propensity score framework analysis (inverse probability of treatment weighting) was used to compare outcomes of the groups while controlling for confounders. RESULTS: During the 16-year study period, 618 patients underwent aortic valve repair. Eight-year survival rate was 92% in the patch group and 90.2% in the no patch group without significant differences [P = 0.957 inverse probability of treatment weighting (IPTW) weighted]. Early valve-related reoperation was more frequent in the patch group as compared to the no patch group (6% vs 1%, P < 0.001 IPTW weighted), the freedom from aortic valve-related reintervention and from structural valve deterioration at 8 years was not significantly different between the patch and no patch groups (93.7% vs 94%, P = 0.968 IPTW weighted; and 99.3% vs 96.7%, P = 0.964 IPTW weighted). CONCLUSIONS: Although a higher rate of early reintervention was observed, aortic valve repair using the pericardial patch, in a standardized approach using external annuloplasty, with effective coaptation height of at least 9 mm, was not associated with an increase in mid-term aortic valve-related reoperation or structural valve deterioration as compared to valve repair without the pericardial patch.

Assessment of tricuspid annulus: anatomic and echocardiographic correlation.

Tricuspid regurgitation is associated with a poor outcome and its quantification remains a challenge. Tricuspid annulus dilatation is one of the parameters that influences clinical decision-making. The aim of this study was to compare the use of 2D transoesophageal echocardiography with surgical assessment for the measurement of the tricuspid annulus. Sixty-one cardiac patients (median age 64 years) were included in the study. Echocardiographic tricuspid annulus measurements were obtained from four chamber and transgastric short axis views and compared with the surgical measurements of this valve. The study was approved by the Ethics Committee of our institution. The tricuspid annulus measurements were obtained from the four chamber and the short axis views in 57 and 49 patients, respectively, while surgical measurement was performed in all 61 patients. Bland-Altman analysis of 49 tricuspid annulus-matched dimensions of the short axis view and surgical values showed a mean bias of 0.223 mm/m2, with limits of agreement of -5.86 to 6.31 mm/m2. Echocardiographic measurements of the tricuspid annulus dimension were accurate (90% sensitivity and 90% specificity for a four chamber view cut-off value ≥ 24.5 mm/m2, and 89% sensitivity and 97% specificity for a short axis view cut-off value ≥ 37.6 mm/m2, P < 0.0001; both cases) for detecting directly assessed annular dilatation by the surgeon in the operative field. Echocardiographic values of tricuspid annulus dimension have a good predictive value to detect surgically assessed annular dilatation and may help identify patients who require surgical tricuspid intervention.

Root repair with aortic ring annuloplasty using the standard approach.

Standardization of aortic valve repair techniques with use of a calibrated annuloplasty have led to improved long-term outcomes in dystrophic aortic insufficiency. It can also improve dissemination of techniques and rates of aortic valve repair. Dystrophic aortic insufficiency can be found in three aortic phenotypes: dilated aortic root, dilated ascending aorta and isolated aortic insufficiency. The aortic annulus is invariably dilated above 25 mm in the vast majority of cases of aortic insufficiency, regardless of whether the aorta is dilated or not. A dilated annulus is a risk factor for late failure of aortic valve repair if not addressed at the time of surgery. We perform a calibrated annuloplasty at both sub- and supra-valvular levels in order to restore the ratio of sinotubular junction and annulus. Current evidence shows aortic valve repair reduces valve-related mortality compared to prosthetic valve replacement, with an improved quality of life.

Peripheral Blood Cell Mitochondrial Dysfunction in Myelodysplastic Syndrome Can Be Improved by a Combination of Coenzyme Q10 and Carnitine.

Structural mitochondrial abnormalities and genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS), yet there is currently little data regarding MDS's metabolic properties and energy production cells. In the current study, we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls. We then assessed the effect of food supplements-Coenzyme Q10 and carnitine on mitochondrial function and hematological response. We show here for the first time that there is a significant impairment of mitochondrial respiration in peripheral blood cells in low-risk MDS, which can be improved with food supplements. We also show that these supplements may improve the cytopenia and quality of life.

Transcatheter Mitral Valve-In-Valve Implantation: An Option for Failed Bioprosthetic Mitral Valve Stenosis During Pregnancy.

A pregnant woman presented with symptomatic bioprosthetic mitral valve stenosis. We discuss the difficulties of decision making in this particular situation where two lives are at stake, the fetus's and the mother's, questioning whether transcatheter mitral valve-in-valve implantation can be an effective and safe option for this challenging condition. (Level of Difficulty: Advanced.).

Systematic echocardiographic assessment of aortic regurgitation-what should the surgeon know for aortic valve repair?

Aortic valve (AV) repair is the preferred surgical treatment in young patients with aortic regurgitation (AR) and/or proximal aorta aneurysm, as noted in the recent European Society of Cardiology (ESC) guidelines. However, this surgical option is still underused in clinical practice. This emphasizes the need to build a heart team dedicated to AV repair with expert surgeons and echocardiographers. Surgical techniques are now standardized in their approaches to enhance the reproducibility and expansion of AV repair. The objective of this keynote is to also demonstrate the need for a standardized pre-pump intra-operative echocardiography protocol to fulfill surgeon's needs in providing a road map and predicting techniques to be used for an effective and durable repair.

Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial.

BACKGROUND: The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. OBJECTIVE: We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. STUDY DESIGN: This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. RESULTS: In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23-1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00-1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. CONCLUSION: There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.

Multiple reoperations on the aortic valve: outcomes and implications for future potential valve-in-valve strategy.

OBJECTIVES: Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. METHODS: From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). RESULTS: There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. CONCLUSIONS: Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

3D transesophageal echocardiography: A new imaging tool for assessment of mitral regurgitation and for guiding percutaneous edge-to-edge mitral valve repair.

Real time three dimensional transesophageal echocardiography (3D TEE) is probably the most powerful and convincing imaging method for understanding the complicated multiform morphology and for evaluating geometry, dynamics and function of degenerative and functional mitral valve (MV) regurgitation. Moreover, color Doppler 3D TEE has been valuable to identify the location of the regurgitant orifice and the severity of the mitral regurgitation. 3D TEE has been shown to be of enormous value in helping surgeons to perform MV repair. In addition, due to its ability to show a "panoramic" view of the "theater" where the procedure takes place, it has become an indispensable companion of 2D TEE during percutaneous edge-to-edge repair. A novel hybrid imaging modality where echocardiography is merged with fluoroscopy, may in the future further improve guidance of this and other complex percutaneous transcatheter interventions.