Animal models of dyssynchrony.

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Journal of Cardiovascular Translational Research (Impact Factor: 3.06). 12/2011; 5(2):135-45. DOI: 10.1007/s12265-011-9336-5
Source: PubMed

ABSTRACT Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT.

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    ABSTRACT: In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: pLBBBvsBaseline < 0.001, pCRTvsBaseline = NS; non-corrected: pLBBBvsBaseline = NS, pCRTvsBaseline = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.
    The international journal of cardiovascular imaging 03/2014; · 2.15 Impact Factor
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    ABSTRACT: About one-third of patients with mild dyssynchronous heart failure suffer from atrial fibrillation (AF). Drugs that convert AF to sinus rhythm may further slowdown ventricular conduction. We aimed to investigate the electrophysiological and haemodynamic effects of vernakalant and flecainide in a canine model of chronic left bundle branch block (LBBB).METHODS AND RESULTS: Left bundle branch block was induced in 12 canines. Four months later, vernakalant or flecainide was administered using a regime, designed to achieve clinically used plasma concentrations of the drugs, n = 6 for each drug. Epicardial electrical contact mapping showed that both drugs uniformly prolonged myocardial conduction time. Vernakalant increased QRS width significantly less than flecainide (17 ± 13 vs. 34 ± 15%, respectively). Nevertheless, both drugs equally decreased LVdP/dtmax by ∼15%, LVdP/dtmin by ∼10%, and left ventricular systolic blood pressure by ∼5% (P = n.s. between drugs).CONCLUSIONS: Vernakalant prolongs ventricular conduction less than flecainide, but both drugs had a similar, moderate negative effect on ventricular contractility and relaxation. Part of these reductions seems to be related to the increase in dyssynchrony.
    Europace 01/2014; · 3.05 Impact Factor
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    ABSTRACT: A strong body of evidence exists to support cardiac resynchronization therapy (CRT) as a mainstay in the management of advanced heart failure for patients with LBBB-type QRS prolongation. Progress in technology has made percutaneous CRT easier to achieve. Skillful operators can readily reach implantation success rates in excess of 95%. Nevertheless, not every patient selected for CRT, according to current criteria, benefits from this therapy. Several factors contribute to the lack of benefit in these patients, including inadequate patient selection, lack of control of atrial arrhythmias, procedural factors and suboptimal pacemaker settings. It remains to be seen whether newer technology and pacing algorithms will increase response rates to CRT. The focus of this review will be to examine which patients benefit most from CRT and to assess methods for optimizing patient selection in order to achieve maximum benefit from this pivotal therapy.
    Expert Review of Cardiovascular Therapy 05/2014; 12(5):573-87.

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