Transcatheter Mitral Valve Replacement in Patients With Previous Aortic Valve Replacement.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) may mature to become a therapeutic option for high-risk patients with severe mitral regurgitation (MR), particularly in patients at high or prohibitive surgical risk. MR patients with preexisting aortic valve prosthesis have been excluded from most TMVR trials because of the potential risks of left ventricular outflow tract obstruction or interaction between the TMVR anchoring mechanism and the aortic prosthesis. We describe the procedural and short-term outcomes of transapical TMVR with the Tiara valve in patients experiencing severe symptomatic MR with previous aortic valve replacement (AVR). METHODS AND RESULTS: Twelve consecutive high surgical risk patients (11 men; mean age, 75±6 years) with aortic valve prosthesis and severe MR underwent TMVR with Tiara valve. Aortic valves were mechanical in 5 and biological in 7 patients, while 1 patient had previously undergone implantation of a transcatheter valve within a failed bioprosthetic surgical valve. Six patients (50%) had undergone redo surgical aortic valve replacement. Clinical characteristics of the group include prior mitral valve repair in 2, prior coronary bypass grafting surgery in 5, chronic atrial fibrillation in 7, renal failure in 9, and pacemaker/cardiac resynchronization device in 9 patients. Mean Society of Thoracic Surgery score and EuroSCORE II were 10.5±4.4 and 12.4±3.7, respectively. Mean baseline left ventricular ejection fraction was 35.5±5.3% (range, 30%-45%). The Tiara valve was implanted uneventfully in all patients. Device migration or left ventricular outflow tract obstruction was not observed. No patient required conversion to open heart surgery or periprocedural hemodynamic support. Procedural success was 100% with no death, MI, stroke, major bleeding, or access site complications at 30 days. MR was eliminated in all 12 patients immediately after implantation. CONCLUSIONS: Transapical mitral valve replacement with the Tiara valve in high-risk patients with severe MR and aortic valve prostheses is technically feasible and can be performed safely.

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling.

RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b-/-) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo-/-) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo-/- mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo-/- mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter-defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.