title: Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.
abstract: OBJECTIVE
  Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.
  
  
  RESULTS
  Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%). Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03) and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001). PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02) and improved endothelial functions (FMD 4.8±1.0%, p<0.0001).
  
  
  CONCLUSIONS
  We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Rammos
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Zeus
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzer
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Kubatz
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Hendgen-Cotta
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Veulemans
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hellhammer
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Totzeck
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Luedike
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006348:Cardiac Surgical Procedures; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008297:Male; D008943:Mitral Valve / Q000503:physiopathology / Q000601:surgery*; D008944:Mitral Valve Insufficiency / Q000097:blood* / Q000503:physiopathology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins