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Optimizing cardiac resynchronization therapy in patients with severe heart failure: identification and detection of stress-induced changes in ventricular conduction delays and development of strategies to compensate for

English title Optimizing cardiac resynchronization therapy in patients with severe heart failure: identification and detection of stress-induced changes in ventricular conduction delays and development of strategies to compensate for
Applicant Osswald Stefan
Number 114708
Funding scheme Project funding (Div. I-III)
Research institution Klinik für Kardiologie Bereich Medizin Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Cardiovascular Research
Start/End 01.10.2006 - 30.09.2008
Approved amount 184'255.00
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Keywords (6)

cardiac resynchronisation therapy (CRT); congestive heart failure; ECG algorhithm; AV-delay; VV-delay; CRT programming

Lay Summary (English)

Lead
Lay summary
In patients with severe systolic heart failure, abnormal electrical conduction (bundle branch block) is associated with dyssynchrony between right and left ventricular contraction and leads to discordant wall motion within the left ventricle. This interventricular dyssynchrony impedes mechanical systolic function of the left ventricle and is associated with adverse clinical outcome. Cardiac resynchronisation therapy (CRT) ameliorates left ventricular (LV) dysfunction and improves long-term outcome of heart failure patients by biventricular (simultaneous right and left ventricular) pacing.However, up to 25% of patients do not improve with this therapy. One explanation might be that all measurements that are undertaken to optimize CRT systems, are obtained during resting conditions. This may lead to underdetection of dyssynchrony that might develop under exercise. Since CRT therapy remains costly, it is of utmost importance to identify the best candidates for this therapy and to lower the non-responder rate. Aim of this research project is to study established parameters of dyssynchrony at rest and during exercise and to develop approaches to ensure optimal long-term resynchronization therapy for all patients in all clinical situations. We propose a set of 3 protocols, of which two are acute studies and one a long-term clinical trial. The surface ECG has been found to reliably predict LV dyssynchrony in patients with very broad QRS-complexes, but is not very sensitive in patients with normal or only mildly prolonged QRS-complexes. In general, Doppler echocardiography with specific techniques is thought to be superior to the surface ECG for the detection and quantification of LV dyssynchrony. In the first acute study, we compare the conventional echocardiographic approach of interventricular delay optimization (VV-programming) against a surface ECG algorithm, which could be incorporated into future CRT devices for automatic optimization. In the second acute study, potential CRT candidates with heart failure and no dyssynchrony at rest will undergo stress echocardiography (semisupine bicycle exercise testing) in order to determine the degree of dyssynchrony developing under exercise conditions. The long-term clinical trial enrols patients with already implanted CRT devices. In large clinical trials it was found that up to 36% of patients received only intermittent resynchronization therapy. This was mainly due to the development of atrial arrhythmias with intrinsic AV-conduction or sinus tachycardia with intrinsic AV-conduction during exercise conditions. Both inhibit biventricular pacing, and thereby jeopardize the potential benefit from CRT in the long-term. In this cohort, elective radiofrequency ablation of the AV-node, which eliminates intrinsic ventricular activation, will be compared to optimal programming of CRT devices in a randomized fashion.Thus, the aim of our research project is to better understand ventricular conduction delays and LV-dyssynchrony at rest, and in particular, during exercise stress. This should help to develop approaches, to optimize biventricular pacing and to lower the non-responder rate.
Direct link to Lay Summary Last update: 21.02.2013

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