Percutaneous edge-to-edge repair of the mitral valve in patients with degenerative versus functional mitral regurgitation.

OBJECTIVES: To prospectively assess the outcome of percutaneous edge-to-edge repair in patients with degenerative versus functional mitral regurgitation (MR). BACKGROUND: The optimal patient population eligible for percutaneous edge-to-edge repair has yet to be defined. METHODS: We analyzed 119 patients treated by percutaneous edge-to-edge repair for symptomatic MR, 72 patients with degenerative and 47 patients with functional MR. The primary endpoints were defined as procedural success (MR grade reduction ≥1 grade) as well as a composite endpoint defined as freedom from MR 3+ or 4+, mitral valve reintervention and death 12 months after clip implantation. In patients with successful clip placement we further analyzed MR grade, New York Heart Association (NYHA) functional class, distance in the 6 min walking test and left ventricular volumes 12 months after clip implantation. RESULTS: The primary success rate of all intended clipping procedures was 83.3% for degenerative and 89.4% for functional MR (P = 0.42). Regarding the composite endpoint we observed an event free survival of 59.7% in patients treated for degenerative MR and 63.8% in patients treated for functional MR (P = 0.73). We observed a highly significant reduction in MR grade as well as improvement in NYHA functional status in both groups 12 months after clip implantation. However, there was a more pronounced MR grade reduction in patients treated for degenerative MR compared with patients treated for functional MR. CONCLUSIONS: Percutaneous edge-to-edge repair of the mitral valve is feasible and comparably effective in patients with degenerative and functional MR.

Three-dimensional transoesophageal echocardiography for the assessment of clip attachment to the leaflets in percutaneous edge-to-edge repair of the mitral valve.

AIMS: Single leaflet clip attachment (SLA) is a prevalent complication in percutaneous edge-to-edge repair of the mitral valve, leading to the recurrence of significant mitral regurgitation. The objective of this retrospective analysis was to evaluate a novel 3-D transoesophageal echocardiographic method for the assessment of clip attachment to the mitral leaflets. METHODS AND RESULTS: We analysed a total of 87 patients treated for symptomatic mitral regurgitation. In 47 patients, clip attachment to the leaflets was assessed by conventional 2-D transoesophageal echocardiography supported by biplane TEE images (biplane TEE group). In 40 patients, clip attachment to the leaflets was assessed by the intraprocedural 3-D volume method in addition to the conventional method (volumetric TEE group). The primary endpoint was defined as clip complications consisting of SLA and clip displacement at any time after clip implantation. Clip complications occurred in nine patients (19.1%) in the biplane TEE group and in two patients (5%) in the volumetric TEE group (p=0.06). Regarding the grade of mitral regurgitation, in the follow-up period we observed a more pronounced deterioration in the biplane TEE group than in the volumetric TEE group. CONCLUSIONS: These findings suggest that the additional use of 3-D volumetric transoesophageal echocardiography for the assessment of clip attachment to the mitral leaflets may contribute to a reduced rate of subsequent clip complications.

Acute beneficial hemodynamic effects of a novel 3D-echocardiographic optimization protocol in cardiac resynchronization therapy.

BACKGROUND: Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming. METHODS: 25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization). RESULTS: EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001). CONCLUSIONS: Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT.

Impact of enhanced external counterpulsation on peripheral circulation.

Enhanced external counterpulsation (EECP) is a noninvasive counterpulsation technique that reduces angina and improves exercise capacity in patients with coronary artery disease. Diastolic coronary perfusion is augmented by pneumatic compression of 3 sets of cuffs wrapped around the lower extremities. Although central hemodynamic changes are well investigated, almost no data exist about the changes of peripheral circulation during EECP. In this study, 12 patients with angina and angiographic evidence of coronary artery disease were treated for 1 hour with EECP. In these patients, peripheral artery disease was excluded by duplex sonography. The patients rested 1 hour before EECP in supine position, and they remained in that position for 1 hour after the procedure. Changes of flow volumes and flow pattern of the posterior tibial artery and the brachial artery were measured by sonography at the end of all 3 periods. Furthermore, we measured the concentration of circulating prostanoids at these 3 time points. Averaged flow volume of the posterior tibial artery decreased to 69% +/- 23% (P < .05) during EECP and increased to 133% +/- 34% (P < .05) of baseline 1 hour after the procedure. In contrast, the averaged flow volume of the brachial artery increased by 9% +/- 4% (P < .05) during EECP and returned to baseline values after EECP. The flow pattern of the posterior tibial artery showed a second early diastolic antegrade flow caused by the cuff inflation and a reverse end-diastolic flow after the deflation of the cuffs. These flow changes caused an increase of the pulsatility index by Gosling (397% during EECP), returning to baseline values in the recovery period. Plasma concentrations of circulating prostanoids showed no significant change during EECP. Thus, pedal flow volume decreased to approximately two thirds of baseline during EECP followed by reactive hyperemia even 1 hour after the procedure; however, this decreased perfusion triggered no change of the prostacyclin/thromboxane ratio and was well tolerated by all investigated patients. The observed 4-fold increase of the peripheral pulsatility index supports the thesis of increase of shear-stress-related improvement of endothelial function during EECP.

Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial.

CONTEXT: Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow-derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells. OBJECTIVE: To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005. INTERVENTIONS: Patients were randomly assigned to receive subcutaneously either a daily dose of 10 microg/kg of G-CSF or placebo for 5 days. MAIN OUTCOME MEASURES: The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis. RESULTS: Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort. CONCLUSION: Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00126100.

Accelerated reperfusion of poorly perfused retinal areas in central retinal artery occlusion and branch retinal artery occlusion after a short treatment with enhanced external counterpulsation.

BACKGROUND: To date, no satisfactory therapy has become available for patients with acute central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO). Enhanced external counterpulsation (EECP) is a new noninvasive procedure that increases perfusion of inner organs. In the current study, the authors measured the impact of EECP on reperfusion in ischemic retinal tissue. METHODS: In a prospective, randomized study, 20 patients with CRAO or BRAO were included. Ten patients were given hemodilution therapy and 2 hours of EECP, and 10 patients were given regular hemodilution therapy only. Quantification of changes in retinal perfusion was carried out by means of scanning laser Doppler flowmetry (in arbitrary units). RESULTS: Enhanced external counterpulsation caused no observable adverse events. A significant increase in perfusion occurred immediately after EECP in the ischemic retinal areas (57 +/- 19 arbitrary units versus 99 +/- 14 arbitrary units). In contrast, no change was measured in the group not treated with EECP (83 +/- 19 arbitrary units versus 89 +/- 44 arbitrary units). Forty-eight hours later, a significant increase in perfusion could be shown in the ischemic retina of both groups, and no significant difference of perfusion was found between the two groups any longer. CONCLUSION: The current study suggests that EECP could be a clinically useful and safe procedure in patients with CRAO or BRAO to accelerate recovery of perfusion in ischemic retinal areas.

Single-dose nimodipine normalizes impaired retinal circulation in normal tension glaucoma.

PURPOSE: Several studies indicate that calcium channel blockers improve the clinical course of normal tension glaucoma (NTG), whereas the underlying mechanism is not fully investigated. Hemodynamic improvement and neuroprotective effects are discussed. In this study, we measured the hemodynamic effects of nimodipine on retinal circulation. PATIENTS AND METHODS: Sixteen patients with NTG and clinical signs of vasospastic hyperreactivity, such as suffering from extremely cold hands and feet, were consecutively selected out of the local glaucoma registry. Ten healthy age-matched volunteers were included as controls. Retinal capillary blood flow was measured by Scanning Laser Doppler Flowmetry in both eyes before and 90 +/- 10 minutes after a single oral dose of 30 mg nimodipine. RESULTS: Before administration of nimodipine, retinal capillary blood flow was significantly reduced in NTG patients compared with controls (262 +/- 80 vs. 487 +/- 164 AU, P < 0.001). Nimodipine increased retinal capillary blood flow in NTG patients by 91 +/- 73% (P < 0.001) to values of healthy controls (440 +/- 113 vs. 439 +/- 123 AU, P = 0.635). In controls, nimodipine did not show significant effects. CONCLUSIONS: In NTG patients with additional vasospastic symptoms, retinal capillary blood is significantly reduced in comparison with healthy controls. Single-dose nimodipine yields to a normalization of retinal circulation in NTG patients up to values of healthy controls 90 minutes after drug administration.