Transcatheter therapy for residual mitral regurgitation after MitraClip therapy.

AIMS: We aimed to examine the effectiveness and the optimal technique for transcatheter therapy for residual mitral regurgitation (MR) after MitraClip therapy with the AMPLATZER Vascular Plug II (AVP-II). METHODS AND RESULTS: Nine patients (mean age, 78±4 years) underwent transcatheter therapy with the AVP-II for residual MR after MitraClip therapy. We examined procedural, in-hospital, and 30-day outcomes. Our technique was successful in all cases, with treatment of different types of residual MR, including paraclip, interclip, and leaflet perforation. MR grade decreased significantly from 4+ to 1+ (p<0.0001), with final residual MR being mild or none in seven patients. Mitral stenosis did not occur with plug placement. The optimal deployment technique for reduction of MR was placement with only one segment on the left atrial side of the mitral valve leaflets (n=8). During clinical follow-up (median 155 days), symptom improvement had occurred in all patients (NYHA class, baseline vs follow-up, 3.2±0.4 vs 2.3±0.8; p=0.01) with mild or no symptoms in six patients. There was no procedural mortality, major adverse event(s), device embolisation, haemolysis or need for cardiac surgery. CONCLUSIONS: For patients with residual MR after MitraClip therapy, this technique may be effective and safe, especially when deployed with only one segment on the left atrial side of the mitral leaflets.

First Experience With Percutaneous Mitral Valve Plication as Primary Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Few therapeutic options exist for patients with severe heart failure due to obstructive hypertrophic cardiomyopathy (HCM) who are at unacceptable surgical risk. We hypothesized that percutaneous plication of the mitral valve could reduce left ventricular outflow tract (LVOT) obstruction and associated mitral regurgitation, thereby leading to amelioration of heart failure symptoms. OBJECTIVES: This study sought to evaluate the potential effectiveness of percutaneous mitral valve plication as a therapy for patients with symptomatic, obstructive HCM. METHODS: Six patients (age 83 ± 8 years; 5 women), judged as not optimal candidates for septal myectomy, were referred for management of severe, drug-refractory heart failure symptoms due to obstructive HCM (New York Heart Association functional class III). Each underwent percutaneous mitral valve leaflet plication to reduce systolic anterior motion (SAM) and mitral regurgitation using the transcatheter mitral clip system. RESULTS: The procedure was completed in 5 patients with placement of a single clip at the A2-P2 segments of the mitral valve. One other patient experienced cardiac tamponade, leading to termination of the procedure. Among the 5 treated patients, percutaneous plication with the eliminated SAM and consequently decreased the intraoperative LVOT gradient (91 ± 44 mm Hg to 12 ± 6 mm Hg; p = 0.007), left atrial pressure (29 ± 11 mm Hg to 20 ± 8 mm Hg; p = 0.06), and mitral regurgitation grade (3.0 ± 0 vs. 0.8 ± 0.4; p = 0.0002) associated with improved cardiac output (in n = 4; 3.0 ± 0.6 l/min to 4.3 ± 1.2 l/min; p = 0.03). Over follow-up of 15 ± 4 months, symptom improvement to New York Heart Association functional class I or II occurred in all patients. Follow-up echocardiography after 15 ± 4 months demonstrated continued absence of SAM and significant reduction in mitral regurgitation, although high systolic LVOT velocities (i.e., >4 m/s) were evident in 3 of the 5 treated patients. CONCLUSIONS: This is a report of percutaneous mitral valve plication as a primary therapy in the management of severely symptomatic, obstructive HCM patients. This initial experience suggests that percutaneous mitral valve plication may be effective for symptom relief in such patients via reduction of SAM and mitral regurgitation. The significance of persistent elevations of LVOT velocities in some patients requires further study.

Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells.

The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.

Oxidative stress and diabetic cardiovascular complications.

Diabetes diagnoses are increasing at an alarming rate worldwide. The majority of diabetes-related deaths arise from cardiovascular complications such as myocardial infarction, stroke, and peripheral vascular disease. Oxidative stress has been demonstrated to be present in animal models as well as in patients with diabetes and has been suggested as a possible contributor to the accelerated atherosclerosis seen in diabetics. The generation of reactive oxygen species in diabetes occurs via several mechanisms and is initiated not only by glucose, but also by other substances that are found at elevated levels in diabetic patients. The resulting oxidative stress leads to a number of proatherogenic events. The elucidation of the mechanisms of oxidative stress in diabetes and their relationship with atherosclerosis could potentially identify molecular targets of therapy for this condition and its cardiovascular consequences.