Michel Zuber

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.

Outcome of pregnancy in women with congenital shunt lesions

OBJECTIVE To evaluate the outcome of pregnancy in women with congenital shunt lesions. SETTING Retrospective study in a tertiary care centre. METHODS Pregnancy history was obtained by a standardised questionnaire and medical records were reviewed. PATIENTS 175 women were identified, at a mean (SD) age of 42 (14) years. Pregnancies occurred in 126 women: 50 with an atrial septal defect, 22 with a ventricular septal defect, 22 with an atrioventricular septal defect, 19 with tetralogy of Fallot, and 13 with other complex shunt lesions. RESULTS 309 pregnancies were reported by 126 woman (2.5 (1.6) pregnancies per woman). The shortening fraction of the systemic ventricle was 40 (8)%, and 98% were in New York Heart Association class I–II at last follow up. Spontaneous abortions occurred in 17% of pregnancies (abortion rate, 0.4 (0.9) per woman). Gestational age of the 241 newborn infants was 8.8 (0.8) months. There were no maternal deaths related to pregnancy. Pre-eclampsia and embolic events were observed in 1.3% and 0.6%, respectively of all pregnancies. Women with complex shunt lesions more often underwent caesarean section (70%v 15–30%, p = 0.005) and gave birth to smaller babies for equivalent gestation (2577 (671) gv 3016 (572) to 3207 (610) g, p < 0.05). The recurrence risk of congenital heart disease was 2.5%. CONCLUSIONS The outcome of pregnancy is favourable in women with congenital shunt lesions if their functional class and their systolic ventricular function are good. Such patients can be reassured.

Cardioband, a transcatheter surgical-like direct mitral valve annuloplasty system: early results of the feasibility trial

AIMS Cardioband system is a direct annuloplasty adjustable device that is implanted in the beating heart on the posterior annulus under fluoroscopic and transoesophageal echocardiographic (TEE) guidance. We report the early (1 month) outcomes of the first-in-man pre-CE-mark feasibility and safety trial. METHODS AND RESULTS The study enrolled high-risk adult individuals at five institutions in Europe with symptomatic secondary mitral regurgitation (MR) despite optimal medical therapy. The primary efficacy endpoints included the technical success rate of implantation, feasibility of the Cardioband adjustment (technical performance), and ability to reduce the annular septolateral dimension and MR grade at hospital discharge and at 30 days. The study group included 31 consecutively enrolled high-risk patients with moderate-to-severe or severe secondary MR with at least 1 month of follow-up (mean age 71.8 ± 6.9 years). All patients received the full implant of a Cardioband. Adjustment of the Cardioband resulted in a significant reduction in the septolateral dimension in all but two patients (septolateral dimension from 36.8 ± 4.8 to 29 ± 5.5 mm after the procedure, P < 0.01). Following Cardioband adjustment (29 of 31 patients) MR was none or trace in 6 (21%), mild in 21 (72%), and moderate in 2 (7%). No patient had severe MR after adjustment. Procedural mortality was zero and in-hospital mortality was 6.5% (2 of 31 patients, neither procedure- nor device-related). At 30 days, 22 of the 25 patients (88%) had MR ≤2+. CONCLUSIONS This study demonstrates the feasibility and safety of percutaneous direct mitral annuloplasty with the Cardioband device in high-risk patients with MR.

Assessment of the Subclavian Vein in Patients with Transvenous Pacemaker Leads

Thrombosis of the subclavian vein can occur after the implantation of transvenous pacemaker electrodes. Although this is seldom followed by thromboembolic complications, it can cause problems when replacing the leads. To assess the impact of the pacemaker leads on the subclavian vein, a study using nonin‐vasive duplex sonography was performed on 56 patients at an average of 41 months after the implantation. Forty‐three percent of the patients were found to have a normal function of the subclavian vein, 46% developed pathological changes of the vessel wall, and 11% occluded. These changes rarelv caused symptoms, and, therefore, had little clinical significance. Moreover, the occlusion rate was found independent of the patients age, the patients sex, the number of electrodes, the procedure of implantation, and even the time from implantation. As a result, the clinical diagnosis of occlusion is uncertain. Therefore, duplex sonography is recommended as an easy means of excluding a totally thrombosed subclavian vein prior to replacing pacemaker leads.

Comparison of different approaches for optimization of atrioventricular and interventricular delay in biventricular pacing

AIMS It has been shown that optimizing atrioventricular (AV) and interventricular (VV) delay improves cardiac performance in patients with biventricular pacemakers. However, there is no standard method for optimization available yet. The aim of this study was to compare echocardiographic parameters-displacement imaging, A wave duration, and aortic velocity time integral (VTI)-and acoustic cardiography derived electromechanical activation time (EMAT) using different approaches of AV and VV delay optimization. We tested whether the initial optimization of the AV interval followed by VV optimization at that optimal AV interval or initial optimization of the VV interval followed by AV optimization at the determined optimal VV interval was accurate and consistent, and how this compared to testing every conceivable combination of AV and VV intervals available. METHODS AND RESULTS A group of 20 patients with biventricular pacemakers was included. Displacement imaging, A wave duration, and aortic VTI were determined at different combinations of AV (100, 150, 200, 250 ms) and VV (RV40, 0, LV40 ms) intervals. If AV duration was determined first, displacement imaging identified the best setting in 8/20, aortic VTI in 10/20, A duration in 13/20, and EMAT in 18/20 patients. With VV duration determined first, the best setting was more difficult to identify regardless of the method used. There was a poor agreement in optimal AV and VV delays of the different methods, and there was no single patient in whom all four methods yielded the same delay combination. CONCLUSION It is advisable to measure a full grid of AV and VV delays to identify optimal settings rather than optimizing one of the two delays first. Different techniques for delay optimization resulted in different optimal delay combinations.

Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.

Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy

AIMS Anderson-Fabry disease affects various organ systems due to glycosphingolipid accumulation. Enzyme replacement therapy (ERT) has been reported to decrease left ventricular wall thickening (LVWT) and to improve diastolic dysfunction. METHODS AND RESULTS This prospective study included 29 patients (patients; mean age 37 +/- 13 years) with genetically, enzymatically and/or biopsy-proven Anderson-Fabry disease and long-time ERT. Data on symptoms, cardiac medications and history of hypertension were collected and all patients had comprehensive echocardiographic examination prior to ERT and at follow-up. Disease was at an early stage with a total mean Mainz severity score index of only 18.6 +/- 13.0. Prior to ERT, 79% of patients reported acroparesthesia. The median creatinine level was 121 +/- 108 mcmol/L and LVWT was present in nine patients (31%). Binary appearance of the interventricular septum was found in 20% and posterobasal fibrosis in 83%. At median follow-up of 37 months, acroparesthesia decreased to 55% (P = 0.016). There was no change in creatinine levels. The incidence of LVWT was unchanged, only an increase in interventricular septal wall thickness from 11.7 +/- 0.4 to 12.5 +/- 0.5 was observed (P = 0.009). Left atrial size and the percentage of patients with binary appearance and posterobasal fibrosis were unchanged. There was a small improvement in diastolic function (29% decrease of E/Ea; P < 0.002). CONCLUSION Our Anderson-Fabry cohort had successful long-time ERT with impressive amelioration of subjective symptoms. Although there was not much improvement in cardiac changes apart from a slight improvement of diastolic function, at least, there was no progression of cardiac disease. For complete reversibility of cardiac changes in Anderson-Fabry disease, ERT might have to be started earlier in life and/or prescribed for a longer time.

Normal reference values of left ventricular strain using three-dimensional speckle tracking echocardiography: results from a multicentre study

AIMS Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population. METHODS AND RESULTS A total of 303 healthy subjects (156 males [51%], between 18 and 82 years of age, ejection fraction [EF] 61 ± 3%), stratified to provide approximately equal proportions of healthy subjects of 18-30, 31-40, 41-50, 51-60, and >60 years of age, underwent 3DSTE. Data were analysed for LV volumes, EF, mass, and global and regional circumferential, longitudinal, radial, and area strain. Significant but small differences between men and women were found for longitudinal and area strains, as well as between different age groups for all LV strain parameters. However, large differences in normal values were observed between different segments, walls, and levels of the LV for radial and longitudinal strains, whereas circumferential and area strains demonstrated generally consistent normal ranges across the LV. CONCLUSIONS Normal ranges of global and regional LV strain using 3DSTE have been established for clinical use. Differences in the magnitude of LV strain are present between men and women as well as different age groups. Moreover, there are differences between different segments, walls, and levels as part of the functional non-uniformity of the normal LV that necessitates the use of segment-specific normal ranges for radial and longitudinal strains. Circumferential and area strains demonstrate the most consistent normal ranges overall.

Acoustic cardiographic parameters and their relationship to invasive hemodynamic measurements in patients with left ventricular systolic dysfunction.

Data obtained at cardiac catheterization were used to evaluate the utility of acoustic cardiographic data in assessing the hemodynamic abnormalities associated with left ventricular systolic dysfunction (LVSD). Thirty-seven patients (mean age, 62.6 years) underwent catheterization, and hemodynamic data were recorded. Acoustic cardiographic recordings were obtained using a system that records and algorithmically interprets diastolic heart sounds and parameters analogous to traditional systolic time intervals. Seventeen patients had LVSD (defined as ejection fraction <50%). The 17 patients with LVSD composed the cohort for analysis. There were strong associations between acoustic cardiographic parameters and left ventricular end-diastolic pressure, ejection fraction, and maximum contractility. Heart rate tended to influence the strength of these correlations. The authors conclude that acoustic cardiographic data can be used in the evaluation of patients with known or suspected LVSD, and specifically in the selection of patients for cardiac resynchronization therapy and the optimization of the settings of implanted resynchronization devices.