AimsThe aim of the present study was to investigate 1 year clinical and functional efficacy of percutaneous mitral valve (MV) repair using MitraClip TM in high-risk surgical patients with symptomatic severe MV regurgitation (MR) and reduced LVEF. Methods and resultsBetween September 2009 and November 2011, 59 patients with reduced EF and severe MR received endovascular MV repair using MitraClip TM . Patients were characterized after 1 and 12 months using echocardiography, 6 min walk test distance, and cardiac biomarkers. The predicted 30-day surgical perioperative mortality rate was 11.4 + 2.2% using the Society of Thoracic Surgeons' score. Complete 1-year clinical follow-up was achieved in 70% of the patients (n ¼ 41; EF 33 + 3%). Percutaneous MV repair resulted in significantly reduced MR and improved NYHA functional class, translating into significantly increased 6 min walk test distance, while high-sensitive troponin T (P , 0.05) and NT-proBNP (non-significant) were reduced. Echocardiography revealed structural reverse remodelling with significantly reduced left atrial volume and LV end-systolic diameter, as well as significantly increased LVEF. These results were consistent in a subgroup of patients with severely reduced LVEF (EF 23 + 2%; n ¼ 25). Thirty-day mortality was 2.9%. ConclusionPercutaneous MV repair using MitraClip TM is a safe technique in high-risk surgical patients, causing significant 1 year reduction of MR which results in structural cardiac reverse remodelling and an increased LVEF. The present data encourage percutaneous MV repair in heart failure patients.--

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Ultrasound targeted microbubble destruction (UTMD) has evolved as a novel system for non-invasive, organ- and tissue-specific drug and gene delivery. Initially developed as ultrasound contrast agents, microbubbles (MBs) have increasingly gained attention for their ability to directly deliver different classes of bioactive substances (e.g. genes, drugs, proteins, gene silencing constructs) to various organ systems and tumors. Bioactive substances can be attached to or incorporated in the microbubble shells. Applying ultrasound at their resonance frequency, microbubbles oscillate. When using higher ultrasound energies, oscillation amplitudes increase, finally resulting in microbubble destruction. This leads to increased capillary and cell membrane permeability in the immediate vicinity of the ruptured MBs, thus facilitating tissue and cell penetration of co-administered or loaded bioactive substances. Numerous proof of principle studies have been performed, demonstrating the broad potential of UTMD as a site-specific, non-invasive therapeutic tool, delivering microbubble payload to various target tissues and organ systems or facilitating uptake of bioactive substances into tissues or cells. This review focuses on current in vivo studies and therapeutic approaches of UTMD. Promising results give hope for future clinical applications of this novel non-viral vector system. Nevertheless, several limitations remain, which will also be discussed in this review article.

In patients with severely reduced systolic LV function undergoing MitraClip™ therapy, procedural safety, efficacy, and clinical improvement after 1 year are comparable to patients with preserved LV function.