Ines Bühler

Intracoronary Injection of Bone Marrow–Derived Mononuclear Cells Early or Late After Acute Myocardial Infarction Effects on Global Left Ventricular Function

Background— Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results— In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71; P=0.73) for the late therapy group. Conclusions— Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry

Background Percutaneous mitral valve repair (MVR) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation (MR) and high operative risk. Objective To identify clinical and periprocedural factors that may have an impact on clinical outcome. Design Multi-centre longitudinal cohort study. Setting Tertiary referral centres. Patients Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerland between March 2009 and April 2011. All of them had moderate–severe (3+) or severe (4+) MR, and 62% had functional MR. 82% of the patients were in New York Heart Association (NYHA) class III/IV, mean left ventricular ejection fraction was 48% and the median European System for Cardiac Operative Risk Evaluation was 16.9%. Interventions MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia. Main outcome measures Clinical, echocardiographic and procedural data were prospectively collected. Results Acute procedural success (APS, defined as successful clip implantation with residual MR grade ≤2+) was achieved in 85% of patients. Overall survival at 6 and 12 months was 89.9% (95% CI 81.8 to 94.6) and 84.6% (95% CI 74.7 to 91.0), respectively. Univariate Cox regression analysis identified APS (p=0.0069) and discharge MR grade (p=0.03) as significant predictors of survival. Conclusions In our consecutive cohort of patients, APS was achieved in 85%. APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR.

Degenerative Aortic Valve Stenosis, but not Coronary Disease, Is Associated With Shorter Telomere Length in the Elderly

Objective—The mechanisms responsible for the age-related increase in the incidence of calcific aortic valve stenosis (CAS) are unclear but may include telomere-driven cellular senescence. Because telomere length varies widely among individuals of the same age, we hypothesized that patients with shorter telomeres would be prone to develop CAS late in life. Methods and Results—Mean telomere length was measured in leukocytes from a cohort of 193 patients ≥70 years of age with and without CAS. Pilot experiments performed in 30 patients with CAS and controls pair-matched for age, sex, and presence or absence of coronary disease demonstrated significantly shorter telomeres in the CAS group both by Southern blot hybridization (5.75±0.55 kbp versus 6.27±0.7 kbp, P=0.0023) and by a quantitative polymerase chain reaction-based technique (relative telomere length 0.88±0.19 versus 1.0±0.19, P=0.01). This finding was then confirmed in the whole cohort (CAS n=64, controls n=129, relative telomere length=0.86±0.16 versus 0.94±0.12, P=0.0003). Both groups were comparable for potential confounding characteristics. Subgroup analysis according to the presence or absence of coronary disease demonstrated no association of this disorder with telomere length. Conclusions—In the elderly, calcific aortic stenosis, but not coronary disease, is associated with shorter leukocyte telomere length.

Real-Time Left Ventricular Pressure-Volume Loops During Percutaneous Mitral Valve Repair With the MitraClip System

Background— Percutaneous mitral valve repair with the MitraClip device has emerged as an alternative to surgery for treating severe mitral regurgitation. However, its effects on left ventricular loading conditions and contractility have not been investigated yet. Methods and Results— Pressure-volume loops were recorded throughout the MitraClip procedure using conductance catheter in 33 patients (mean age, 78±10 years) with functional (45%), degenerative (48%), or mixed (6%) mitral regurgitation. Percutaneous mitral valve repair increased end-systolic wall stress (WSES; from [median] 184 mm Hg [interquartile range (IQR), 140–200 mm Hg] to 209 mm Hg [IQR, 176–232 mm Hg]; P=0.001) and decreased end-diastolic WS (WSED; from 48 mm Hg [IQR, 28–58 mm Hg] to 34 mm Hg [IQR, 21–46 mm Hg]; P=0.005), whereas the end-systolic pressure-volume relationship was not significantly affected. Conversely, cardiac index increased (from 2.6 L·min−1·m−2 [IQR, 2.2–3.0 L·min−1·m−2] to 3.2 L·min−1·m−2 [IQR, 2.6–3.8 L·min−1·m−2]; P<0.001) and mean pulmonary capillary wedge pressure decreased (from 15 mm Hg [IQR, 12–20 mm Hg] to 12 mm Hg [IQR, 10–13 mm Hg]; P<0.001). Although changes in WSES were not correlated with changes in cardiac index, changes in WSED correlated significantly with changes in mean pulmonary capillary wedge pressure (r=0.63, P<0.001). Total mechanical energy assessed by the pressure-volume area remained unchanged, resulting in a more favorable index of forward output (cardiac index) to mechanical energy (pressure-volume area) after mitral valve repair. On follow-up (153±94 days), New York Heart Association functional class was reduced from 2.9±0.6 to 1.9±0.5 (P<0.001) at 3 months, and echocardiographic follow-up documented a stepwise reduction in end-diastolic volume (from 147 mL [IQR, 95–191 mL] to 127 mL [IQR, 82–202 mL]; P=0.036). Conclusions— Percutaneous mitral valve repair improves hemodynamic profiles and induces reverse left ventricular remodeling by reducing left ventricular preload while preserving contractility. In nonsurgical candidates with compromised left ventricular function, MitraClip therapy could be considered an alternative to surgical mitral valve repair.

Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results.

RATIONALE Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE To demonstrate long-term efficacy of BM-MNC treatment after AMI. METHODS AND RESULTS In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

The Effect of Bone Marrow Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results

RATIONALE Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE To demonstrate long-term efficacy of BM-MNC treatment after AMI. METHODS AND RESULTS In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9±9.8% for control (mean±SD), -0.9±10.5% for the early treatment group, and -0.7±10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Integrated x-ray and echocardiography imaging for structural heart interventions.

Treatment of structural heart disease (SHD) represents a growing need and, with increasing device availability, an increasing number of SHD can be and will be treated percutaneously. However, interventional treatment of SHD is challenging. Long procedure times and steep learning curves are recognised obstacles. The main difficulties arise, however, from the inability to visualise simultaneously the anatomy and the devices using a single imaging technology. In fact, the majority of percutaneous interventions in SHD are guided by fluoroscopy. On the other hand, a multitude of imaging technologies are presently available to guide the interventionalist. Of these technologies, transoesophageal echocardiography (TEE), and particularly 3-D TEE, is rapidly becoming the imaging modality of choice for many of these procedures because it provides critical insights into soft tissue anatomy. However, adequate visualisation and appreciation of the relationships between the cardiac structures and the devices using various imaging modalities remain a challenge. Hence, the interaction between the operator and imager is a crucial factor in attaining procedural success. Innovative technology that fuses live 3-D TEE with live x-ray in an intuitive way could have an important added value. This new imaging technology seeks to improve the communication between the echocardiographer and the interventionalist, to increase the confidence and anatomical awareness, to assist in guidance, and to increase procedural efficiency.

Intracoronary Injection of Bone Marrow Derived Mononuclear Cells, Early or Late after Acute Myocardial Infarction: Effects on Global Left Ventricular Function Four months results of the SWISS-AMI trial

Background— Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results— In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71; P=0.73) for the late therapy group. Conclusions— Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Effective orifice area and hemodynamic performance of the transcatheter Edwards Sapien 3 prosthesis: short-term and 1-year follow-up

Aims The Edwards Sapien 3 heart valve prosthesis (S3) is commonly used for transcatheter aortic valve implantation (TAVI) and is available in three sizes. To date no data has been published on the effective orifice area (EOA) and the hemodynamic performance of the three different S3 sizes. The aim of this study was to measure the size-specific EOA and hemodynamic performance of the S3 in short-term and 1-year follow-up. Methods and results One hundred and thirteen consecutive patients treated by TAVI with a S3 prosthesis at the Heart Clinic Zurich between May 2014 and July 2015 were included. Clinical data were extracted from the Swiss TAVI registry. The EOA was calculated using Doppler echocardiography (peri-interventionally and at discharge) and by 3D-biplane transoesophageal echocardiography (peri-interventionally). Mean transvalvular gradients (dPmean) were additionally calculated with Doppler echocardiography at 30 days and 1 year. Results were analysed separately for the 23 mm (n = 42; 37%), 26 mm (n = 46; 41%), and 29 mm (n = 25; 22%) prostheses. At discharge, the EOAs were 1.6 ± 0.2 cm2 (23 mm S3), 2.0 ± 0.2 cm2 (26 mm S3), and 2.7 ± 0.2 cm2 (29 mm S3), p < 0.001. The dPmeans at discharge were 10.9 ± 6.0 mmHg (23 mm S3), 10.4 ± 3.5 mmHg (26 mm S3), and 8.9 ± 2.8 mmHg (29 mm S3), p = 0.235, and did not significantly change over time within any of the S3 sizes. Conclusions Post-TAVI, the EOAs of the three different S3 prosthesis sizes differ significantly, the transvalvular gradients, however, are comparable. Mean transvalvular gradients remain stable over time and document good prosthesis function after 1 year.

Intracoronary Injection of Bone Marrow–Derived Mononuclear Cells Early or Late After Acute Myocardial InfarctionClinical Perspective

Background— Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results— In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71; P=0.73) for the late therapy group. Conclusions— Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.