Transapical off-pump mitral valve repair (MVr) with NeoChord implantation has become widely applied in Europe for patients presenting with severe mitral regurgitation due to leaflet prolapse or flail. The procedure is performed under real-time 2D-and 3D-transesophageal echocardiography (TEE) for both implantation and neochordae tension adjustment allowing real-time monitoring of hemodynamic recovery. Preoperative anatomic and echocardiographic selection criteria, procedure refinement, as well as innovative ex-vivo surgical simulator training have been developed and strategically employed in the past few years, to generate a robust precision-based procedural framework with significantly enhanced operator use, patient safety and clinical outcomes. The procedure has evolved into a reproducibly successful and safe approach, which complements existing surgical treatment strategies available to eligible patients with chronic severe degenerative mitral regurgitation.

Background: The NeoChord echo-guided transapical beating heart repair is a promising early-stage minimally invasive surgical procedure for degenerative mitral valve (MV) regurgitation (DMR) correction. The technique has been improved since its inception following procedure standardization, patient selection optimization, and learning curve stabilization. We hereby present the mid-term clinical results through three years of our large single center experience. Methods: All consecutive patients with severe symptomatic DMR due to prolapse or flail of one or both mitral leaflets that underwent the NeoChord procedure between November 2013 and June 2019 were included. Patients were categorized according to MV anatomy; Type A isolated central posterior leaflet prolapse and/or flail, Type B posterior multi-segment prolapse and/or flail, Type C anterior and/or bi-leaflet prolapse or flail, Type D paracommissural prolapse and/or flail and/or significant leaflet and/or annular calcifications. Patients underwent clinical and echocardiographic follow-up at one, three, six, twelve months and yearly thereafter. Clinical outcomes and the composite primary endpoint (patient success) were defined according to Mitral Valve Academic Research Consortium (MVARC) criteria. Mitral regurgitation (MR) severity was graded as absent, mild, moderate and severe according to American Society of Echocardiography (ASE) and European Society of Cardiology (ESC) guidelines. Results: Two hundred and three patients were included; median follow-up was 24 months [interquartile range (IQR), 9-36]. Median age was 64 years (IQR, 54-74 years), median Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) was 0.60% (IQR, 0.32-1.44%). There were 106 Type A patients (52.2%), 68 Type B (33.5%), 16 Type C (7.9%), and 13 Type D (6.4%). Kaplan-Meier estimate of survival was 99.0%±0.7% at one and two years and 94.0%±2.9% at three years. At one-year follow-up patient success was 91.2%±2.0% and 111 patients (74%) presented a residual MR mild or less (1+). At three-year follow-up patient success was 81.2%±3.8% and 32 patients (64%) had a residual MR mild or less (1+). Patient success was significantly different according to anatomical type (P=0.001). Echocardiographic analysis showed a significant acute left ventricle and left atrial reverse remodeling that was maintained up to three years. Conclusions: The NeoChord echo-guided transapical beating heart repair procedure demonstrated good clinical outcomes and echocardiographic results up to three-year follow-up.

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In a previous investigation carried out in this Laboratory (Beloff-Chain et al. 1953) it was found that isolated rat diaphragm synthesized glycogen from glucose and from glucose 1 -phosphate to about the same extent when the substrate concentration, calculated as glucose, was 2 %. There was little or no glycogen synthesis from glucose 6-phosphate at this concentration. Further, it was shown that insulin had no stimulatory effect on glycogen synthesis from glucose 1-phosphate as it had from glucose.

Background and Aim of the study Micro‐invasive cardiac surgery identifies procedures performed off‐pump, on beating heart. Aim of this single‐center retrospective study was to assess early outcomes of a totally micro‐invasive strategy (percutaneous coronary intervention—PCI—followed by transapical off‐pump NeoChord mitral repair) in patients with concomitant coronary artery disease (CAD) and degenerative mitral regurgitation (MR). Methods We analyzed early and 1‐year follow‐up data of patients who underwent a NeoChord procedure between November 2013 and May 2020, and preceded by PCI. Outcomes were defined according to Mitral Valve Academic Research Consortium (MVARC) definitions. Results Among 220 patients who underwent NeoChord repair in the study period, 17 (7.7%) underwent PCI previously. CAD was an accidental finding during preoperative mitral evaluation in nine patients (52.9%; Group 1; with PCI occurring 2 months before NeoChord, interquartile range [IQR] = 1.0–2.7), while it was part of the past medical history in the remaining eight patients (47.1%; Group 2; with PCI occurring 30 months before NeoChord, IQR = 24.5–64.0). Twelve patients (70.6%) presented single‐vessel disease, two patients (11.8%) triple‐vessel disease. No surgical revisions for bleeding were required after NeoChord. At 1‐year follow‐up (n = 16), all patients were alive and did not experience major adverse events except for one reoperation due to late NeoChord failure. None required additional PCI. Conclusion In our experience, PCI before NeoChord seems safe and effective, and performing PCI before NeoChord might not affect outcomes. A totally micro‐invasive strategy in selected patients suffering from MR and CAD should be considered as a reasonable alternative to conventional surgery.

1. The influence of ATP on glucose metabolism was studied in the isolated rat diaphragm; it was shown that ATP increases the oxidation of glucose and the aerobic conversion of glucose into lactate, whereas it decreases glycogen synthesis. There was no influence of ATP on the anaerobic formation of lactate from glucose. 2. A maximum effect of ATP on the oxidation of glucose (about 160% increase) was obtained in the presence of 10mm-ATP; in the presence of 2mm-ATP the effect was about 65%, and was approximately constant from 10 to 90min. incubation period. 3. In a phosphate-free tris-buffered medium the oxidation of glucose was considerably decreased, but the percentage stimulation by ATP was about the same as in a phosphate-buffered medium. 4. ATP was shown to increase the oxidation of fructose, glucose 6-phosphate, glucose 1-phosphate, fructose 1,6-diphosphate and, to a much smaller extent, pyruvate. 5. ADP stimulated the oxidation of glucose to the same extent as ATP at a concentration of 2mm and the effect with AMP was only slightly less; IMP and adenosine had only a small stimulatory effect at this concentration, whereas inosine had no effect.

Metabolism of Hexose Phosphate Esters * Some of these results have been previously published in a preliminary note (Beloff-Chain, Bovet, Chain & Pocchiari, 1951),. After our preliminary publication Kuether (1951) reported results of similar but less detailed experiments carried out with glucose 1-phosphate on ailoxan-diabetic rats. His findings and conclusions were very similar to our own. 34 529 A. BELOFF-CHAIN AND OTHERS Studies with the isolated diaphragm from alloxandiabetic rats are now in progress and will be reported later. METHODS AND MATERIAL Preparations Glucose l-pho8phate (G1-P). The dipotassium salt was prepared according to the method of McCready & Hassid (1944) using the cation-exchange resin Zeo-Karb 215 and the anion-exchange resin De-Acidite B, or the corresponding Amberlite resins. Gluco8e 6-phoosphate (G06-P). The barium salt was prepared according to the method of Seegmiller & Horecker (1951) from glucose and tetraphosphoric acid (Cherbuliez & Weniger, 1946). Fructose 1:6-diphosphate (F1:6-P). The barium salt was prepared according to the method of Neuberg & Lustig (1942) from brewer's yeast. Fructose 6-phosphate (F6-P). The barium salt was prepared from F 1:6-P by hydrolysis in i-HBr for 5 days at 320 according to the method of Neuberg, Lustig & Rothenberg (1943).

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