Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

Impact of simulator-based training on acquisition of transthoracic echocardiography skills in medical students.

Introduction: Due to the expanding role of ultrasound as a diagnostic tool in modern medicine, medical schools rapidly include ultrasound training in their curriculum. The objective of this study was to compare simulator-based training along with classical teaching, using human models, to impart focused transthoracic echocardiography examination. Subject and Methods: A total of 22 medical students, with no former transthoracic echocardiography training, undertook a 90-min e-learning module, dealing with focused echocardiography and important echocardiographic pathologies. Subsequently, they had to complete a multiple-choice-questioner, followed by a 120-min practical training session either on the Heartworks™, (Cardiff, UK) and the CAE Vimedix®, (Québec, Canada) simulator (n = 10) or on a live human model (n = 12). Finally, both groups had to complete a post-test consisting of ten video-based multiple-choice-questions and a time-based, focused echocardiography examination on another human model. Two blinded expert observers scored each acquired loop which recorded 2 s of each standard view. Statistical analysis was performed with SPPS 24 (SPSS™ 24, IBM, USA) using the Mann-Whitney-Test to compare both groups. Results: Analysis of measurable outcome skills showed no significant difference between transthoracic echocardiography training on human models and high-fidelity simulators for undergraduate medical students. Conclusions: Both teaching methods are effective and lead to the intended level of knowledge and skills.

Transcatheter edge-to-edge mitral valve repair with the PASCAL system: early results from a real-world series.

AIMS: This study sought to characterise the real-world performance and clinical outcomes of the PASCAL system, a leaflet approximation device for transcatheter mitral valve repair. METHODS AND RESULTS: Fifty patients in NYHA Class II-IV despite optimal medical therapy (median age 78.0 years [IQR 74.5-81.0], 52% female, log EuroSCORE 21.6 [IQR 13.2-30.2]) were treated for severe mitral regurgitation (MR) and followed up for one month. Primary and secondary MR was present in 24% and 68% of patients, respectively, with a mixed aetiology observed in 8%. A 1-device strategy was employed in 26/50 patients (52%), a 2-device strategy in 23/50 (46%) patients, and a 3-device strategy in 1/50 (2%) patients. Technical and procedural success was achieved in 100% and 98% of patients, respectively. MR grade ≤1 was observed in 39/50 (78%) patients at discharge, and in 36/46 (78%) patients at one month, with transvalvular gradients remaining ≤5 mmHg in all patients. One device embolisation and one single leaflet device attachment were observed during follow-up. After one month, 73% of patients reported an improvement in NYHA class, and six-minute walk test distance increased by 73±12 m in patients without relevant tricuspid regurgitation. CONCLUSIONS: In a real-world population, the PASCAL device effectively reduces MR and leads to functional improvements on short-term follow-up.

Changes in dynamic mitral valve geometry during percutaneous edge-edge mitral valve repair with the MitraClip system.

BACKGROUND: The aim of this study was to quantify the acute dynamic changes of mitral valve (MV) geometry throughout the cardiac cycle-during percutaneous MV repair with the MitraClip system by 3-dimensional transesophageal echocardiography (3D TEE). METHODS: The MV was imaged throughout the cardiac cycle (CC) before and after the MitraClip procedure using 3D TEE in 28 patients (mean age, 77 ± 8 years) with functional mitral regurgitation (FMR). Dynamic changes in the MV annulus geometry and anatomical MV orifice area (AMVOA) were quantified using a novel semi-automated software. RESULTS: Percutaneous MV repair decreased anterior-posterior diameter by up to 9% (at 50% of CC; from 34.5 to 31.9 mm; p < 0.001) throughout the CC and increased the diastolic lateral-medial diameter by up to 7% (at 60% of the CC; from 39.7 to 42.3 mm; p < 0.001), whereas the annular circumference and area were not significantly affected. Annulus sphericity index was reduced up to 13% (at 50% of the CC; from 0.89 to 0.78, p < 0.001). The AMVOA also decreased during systole, the maximum decrease being from 0.6 to 0.2 mm2 (at 0% of CC; p = 0.007), and during diastole the maximum decrease being from 4.6 to 1.6 cm2 (at 50% of CC; p < 0.001). CONCLUSIONS: Percutaneous MV repair reduces the MR by an improved coaptation of MV leaflets joint with a simultaneous indirect reduction of anterior-posterior diameter. Further, the MitraClip procedure leads to a reduction of AMVOA of more than 60% during diastole.

Transcatheter treatment of tricuspid regurgitation using edge-to-edge repair: procedural results, clinical implications and predictors of success.

AIMS: The aim of this study was to analyse the feasibility, safety and effectiveness of tricuspid valve (TV) repair using the MitraClip system in patients at high surgical risk. METHODS AND RESULTS: Forty-two elderly high-risk patients (76.8±7.3 years, EuroSCORE II 8.1±5.7) with isolated TR or combined TR and mitral regurgitation (MR) underwent edge-to-edge repair of the TV (n=11) or combined edge-to-edge repair of the TV and mitral valve (n=31). Procedural details, success rate, impact on TR severity and predictors of success at 30-day follow-up were analysed. Successful edge-to-edge repair of TR was achieved in 35/42 patients (83%, 68 clips in total, 94% in the anteroseptal commissure, 6% in the posteroseptal commissure). In five patients, grasping of the leaflets was impossible and two patients had no decrease in TR after clipping. In those with procedural success, clipping of the TV led to a reduction in effective regurgitant orifice area by -62.5% (from 0.8±0.4 to 0.3±0.2 cm2; p<0.0001). In both patients with isolated TV and combined procedures, six-minute walking distance improved (from 285±118 to 344±81 m and from 225±113 to 261±130 m, p=0.02 and 0.03, respectively). Predominant anteroseptal or central TR was identified as a predictor of procedural success (p=0.025). CONCLUSIONS: Edge-to-edge repair of the TV is feasible with a promising reduction in TR, which could result in clinical improvement.

Retrospective study of complete atrioventricular canal defects: Anesthetic and perioperative challenges.

OBJECTIVE: The objective of this study was to highlight anesthetic and perioperative management and the outcomes of infants with complete atrioventricular (AV) canal defects. DESIGN: This retrospective descriptive study included children who underwent staged and primary biventricular repair for complete AV canal defects from 1999 to 2013. SETTING: A single-center study at a university affiliated heart center. PARTICIPANTS: One hundred and fifty-seven patients with a mean age at surgery of 125 ± 56.9 days were included in the study. About 63.6% of them were diagnosed as Down syndrome. Mean body weight at surgery was 5.6 ± 6.3 kg. METHODS: Primary and staged biventricular repair of complete AV canal defects. MEASUREMENTS AND MAIN RESULTS: A predefined protocol including timing of surgery, management of induction and maintenance of anesthesia, cardiopulmonary bypass, and perioperative intensive care treatment was used throughout the study. Demographic data as well as intraoperative and perioperative Intensive Care Unit (ICU) data, such as length of stay in ICU, total duration of ventilation including reintubations, and total length of stay in hospital and in hospital mortality, were collected from the clinical information system. Pulmonary hypertension was noted in 60% of patients from which 30% needed nitric oxide therapy. Nearly 2.5% of patients needed permanent pacemaker implantation. Thorax was closed secondarily in 7% of patients. In 3.8% of patients, reoperations due to residual defects were undertaken. Duration of hospital stay was 14.5 ± 4.7 days. The in-hospital mortality was 0%. CONCLUSION: Protocolized perioperative management leads to excellent outcome in AV canal defect repair surgery.

Feasibility of measurements of valve dimensions in en-face-3D transesophageal echocardiography.

Newest 3D software allows measurements directly in the en-face-3D TEE mode. Aim of the study was to ascertain whether measurements performed in the en-face-3D TEE mode are comparable with conventional measurement methods based on 2D TEE and 3D using the multiple plane reconstruction mode with the Qlab® software. En-face-3D TEE is used more frequently in daily clinical routine during cardiac operations. So far measurements could only be done based on 2D images or with the use of multi planar reconstruction mode with additional software. Measurement directly in the 3D image (en-face-3D TEE) would make measurements faster and easier to use in clinical practice. After approval by the local ethic committee and written informed consent from the patients additionally to a comprehensive perioperative 2D TEE examination a real time (RT) 3D zoom- dataset was recorded. Routine measurements of the length of anterior and posterior mitral valve leaflets as well as mitral valve and aortic valve areas were performed in en-face-3D TEE, multiplanar reconstruction mode using Qlab®-software (Philips, Netherlands) and 2D TEE standard views. Twenty nine patients with a mean age of 67 years undergoing elective cardiac surgery/interventions were enrolled in this study. Direct measurements in en-face-3D TEE mode lead to non significant underestimation of all parameters as compared to Qlab® and 2D TEE measurements. Measurements in en-face-3D TEE are feasible but lead to non significant underestimation compared to measurements performed with Qlab® or in 2D TEE views.

Analysis of circumflex artery anatomy by real time 3D transesophageal echocardiography compared to cardiac computed tomography.

Iatrogenic injury to the circumflex artery (Cx) due to its close proximity to the mitral annulus is a rare but dreadful complication that can occur during mitral valve repair. The aim of our study was to compare multiple measurements of the Cx datasets, obtained by real time three-dimensional transesophageal echocardiography (RT3D TEE) and corresponding measurements assessed in multi-planar three-dimensional images acquired by multidetector computed tomography (MDCT). Preoperative RT3D TEE and MDCT datasets of 25 patients who had previously undergone minimally invasive mitral valve surgery were retrospectively analyzed. The vessel diameter and the horizontal as well as vertical distances from the center of the Cx to the mitral valve annulus were measured. Horizontal as well as vertical Cx distances showed a strong correlation between measurements of RT3D TEE and MDCT whereas the measurements of the Cx diameter showed no correlation. Measurements of horizontal and vertical distances of the Cx to the mitral annulus can be performed using RT3D TEE and show good correlation with MDCT-based measurements.

TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.

CONTEXT: The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role. OBJECTIVE: We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies. DESIGN/SETTING/PARTICIPANTS: Immunoglobulins were purified from the sera of 57 GO patients (GO-Igs) and tested for their ability to activate TSHR and/or IGF-1R directly and TSHR/IGF-1R cross talk in primary cultures of GOFs. Cells were treated with M22 or GO-Igs with or without IGF-1R inhibitory antibodies or linsitinib, an IGF-1R kinase inhibitor. MAIN OUTCOME MEASURES: Hyaluronan (hyaluronic acid [HA]) secretion was measured as a major biological response for GOF stimulation. IGF-1R autophosphorylation was used as a measure of direct IGF-1R activation. TSHR activation was determined through cAMP production. RESULTS: A total of 42 out of 57 GO-Ig samples stimulated HA secretion. None of the GO-Ig samples exhibited evidence for IGF-1R autophosphorylation. Both anti-IGF-1R antibodies completely inhibited IGF-1 stimulation of HA secretion. By contrast, only 1 IGF-1R antibody partially blocked HA secretion stimulated by M22 or GO-Igs in a manner similar to linsitinib, whereas the other IGF-1R antibody had no effect on M22 or GO-Ig stimulation. These findings show that the IGF-1R is involved in GO-Igs stimulation of HA secretion without direct activation of IGF-1R. CONCLUSIONS: IGF-1R activation by GO-Igs occurs via TSHR/IGF-1R cross talk rather than direct binding to IGF-1R, and this cross talk is important in the pathogenesis of GO.