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Sanders-Van Wijk S.,Maastricht University | Muzzarelli S.,University of Basel | Muzzarelli S.,Cardiocentro Ticino | Neuhaus M.,Kantonsspital Baden | And 8 more authors.
European Journal of Heart Failure | Year: 2013

Aims: NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed. Methods and results: A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT-proBNP-guided or symptom-guided therapy and ≥1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8-9.4) vs. 5.4 (2.7-11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0-2.7) vs. 1.3 (0-3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects - although small and related to non-severe AEs only - were only seen in the older and more co-morbid patients. Conclusion: sNT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients. © The Author 2013. Source

Bacharova L.,International Laser Center | Mateasik A.,International Laser Center | Krause R.,University of Lugano | Prinzen F.W.,Maastricht University | And 2 more authors.
Journal of Electrocardiology | Year: 2011

Background: The electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH) is based on the assumption that QRS voltage increases with left ventricular mass. However, most of patients with echocardiographically detected LVH do not have increased QRS voltage. Reduced intercellular coupling has been observed in LVH patients and animal models. The purpose of this study was to show that this uncoupling can explain relatively low QRS voltage in LVH patients. Methods: Electrocardiograms and vectorcardiograms (VCG) were simulated with a realistic large-scale computer model of the human heart and torso that reliably represented the effects of reduced coupling on both propagation and ECG voltage. Results: Uncoupling reduced QRS voltage in all leads except aVL, reflecting a decrease in vector amplitude as well as a leftward axis deviation that suggested left anterior fascicular block. Conclusions: Low QRS voltage does not necessarily contradict a diagnosis of LVH but may be an indication for electrical uncoupling. The diagnostic value of this "relative voltage deficit" needs to be demonstrated in clinical studies. © 2011 Elsevier Inc. Source

Kappenberger L.,Cardiocentro Ticino
European Heart Journal | Year: 2013

Atrial fibrillation (AF) is the most common arrhythmia and among the leading causes of stroke and heart failure in Western populations. Despite the increasing size of clinical trials assessing the efficacy and safety of AF therapies, achieved outcomes have not always matched expectations. Considering that AF is a symptom of many possible underlying diseases, clinical research for this arrhythmia should take into account their respective pathophysiology. Accordingly, the definition of the study populations to be included should rely on the established as well as on the new classifications of AF and take advantage from a differentiated look at the AF-electrocardiogram and from increasingly large spectrum of biomarkers. Such an integrated approach could bring researchers and treating physicians one step closer to the ultimate vision of personalized therapy, which, in this case, means an AF therapy based on refined diagnostic elements in accordance with scientific evidence gathered from clinical trials. By applying clear-cut patient inclusion criteria, future studies will be of smaller size and thus of lower cost. In addition, the findings from such studies will be of greater predictive value at the individual patient level, allowing for pinpointed therapeutic decisions in daily practice. © The Author 2013. Source

Strik M.,Maastricht University | Van Middendorp L.B.,Maastricht University | Houthuizen P.,Maastricht University | Ploux S.,Maastricht University | And 4 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2013

Background: The relative contribution of electromechanical synchronization and ventricular filling to the optimal hemodynamic effect in cardiac resynchronization therapy (CRT) during adjustment of stimulation-timings is incompletely understood. We investigated whether optimal hemodynamic effect in CRT requires collision of pacing-induced and intrinsic activation waves and optimal filling of the left ventricle (LV). Methods and Results: CRT was performed in dogs with chronic left bundle-branch block (n=8) or atrioventricular (AV) block (n=6) through atrial (A), right ventricular (RV) apex, and LV-basolateral pacing. A 100 randomized combinations of A-LV/A-RV intervals were tested. Total activation time (TAT) was calculated from >100 contact mapping electrodes. Mechanical interventricular dyssynchrony was determined as the time delay between upslopes of LV and RV pressure curves. Settings providing an increase in LVdP/dtmax (maximal rate of rise of left ventricular pressure) of ≥90% of the maximum LVdP/dtmax value were defined as optimal (CRTopt). Filling was assessed by changes in LV end-diastolic volume (EDV; conductance catheter technique). In all hearts, CRTopt was observed during multiple settings, providing an average LVdP/dtmax increase of ≈15%. In AV-block hearts, CRT opt exclusively depended on interventricular-interval and not on AV-interval. In left bundle-branch block hearts, CRTopt occurred at A-LV intervals that allowed fusion of LV-pacing-derived activation with right bundle-derived activation. In all animals, CRTopt occurred at settings resulting in the largest decrease in TAT and mechanical interventricular dyssynchrony, whereas LV EDV hardly changed. Conclusions: In left bundle-branch block and AV-block hearts, optimal hemodynamic effect of CRT depends on optimal interplay between pacing-induced and intrinsic activation waves and the corresponding mechanical resynchronization rather than filling. © 2013 American Heart Association, Inc. Source

Jeger R.,University of Basel | Jaguszewski M.,University of Zurich | Nallamothu B.N.,University of Michigan | Luscher T.F.,University of Zurich | And 4 more authors.
International Journal of Cardiology | Year: 2014

Background The optimal strategy for percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) in multi-vessel disease (MVD), i.e., multi-vessel PCI (MV-PCI) vs. PCI of the infarct-related artery only (IRA-PCI), still remains unknown. Methods Patients of the AMIS Plus registry admitted with an acute coronary syndrome were contacted after a median of 378 days (interquartile range 371-409). The primary end-point was all-cause death. The secondary end-point included all major adverse cardiovascular and cerebrovascular events (MACCE) including death, re-infarction, re-hospitalization for cardiac causes, any cardiac re-intervention, and stroke. Results Between 2005 and 2012, 8330 STEMI patients were identified, of whom 1909 (24%) had MVD. Of these, 442 (23%) received MV-PCI and 1467 (77%) IRA-PCI. While all-cause mortality was similar in both groups (2.7% both, p > 0.99), MACCE was significantly lower after MV-PCI vs. IRA-PCI (15.6% vs. 20.0%, p = 0.038), mainly driven by lower rates of cardiac re-hospitalization and cardiac re-intervention. Patients undergoing MV-PCI with drug-eluting stents had lower rates of all-cause mortality (2.1% vs. 7.4%, p = 0.026) and MACCE (14.1% vs. 25.9%, p = 0.042) compared with those receiving bare metal stents (BMS). In multivariate analysis, MV-PCI (odds ratio, OR 0.69, 95% CI 0.51-0.93, p = 0.017) and comorbidities (Charlson index ≥ 2; OR 1.42, 95% CI 1.05-1.92, p = 0.025) were independent predictors for 1-year MACCE. Conclusion In an unselected nationwide real-world cohort, an approach using immediate complete revascularization may be beneficial in STEMI patients with MVD regarding MACCE, specifically when drug-eluting stents are used, but not regarding mortality. This has to be tested in a randomized controlled trial. © 2014 Elsevier Ireland Ltd. Source

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