Animal models of dyssynchrony

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.

Fig. 1

Creation of left bundle branch through radiofrequency ablation: on the electrogram derived from a standard ablation catheter, introduced through the aortic valve into the LV, the left bundle branch potential is observed as a sharp deflection between the A-wave and V-wave in the local electrograms (bottom tracing). Subsequently, ablation is started at this location, which results in a proximal LBBB. The top tracing shows a simultaneously recorded surface electrocardiogram

Fig. 2

Typical examples of 3D electrical activation in canine hearts during normal conduction (left panel) and after creation of LBBB (right panel). Plotted activation times were derived from ≈110 epicardial and endocardial contact electrodes and referenced to the onset of the Q wave. In the right panel, the ablation catheter is shown with the approximate location of ablation after which a LBBB pattern occurred

Fig. 3

Effects of synchronous (top) and asynchronous (bottom) ventricular activation. Asynchronous electromechanical activation induces increased QRS duration (a) mechanical interventricular assynchrony (b) and onset of LV shortening (strain) is regionally delayed (negative deflection of curve) (c). Adapted with permission from Verbeek et al. [13]

Fig. 4

Typical example of myocardial circumferential shortening (%) tracings in eight regions along the mid-basal LV circumference. Please note the abnormal shortening patterns during LBBB and the normalization during CRT (LBBB + CRT)

Fig. 5

Short-axis slice at the mid-level of LV demonstrating transmural myocardial infarction of the canine LV lateral wall in the LBBB + infarction model (for details see text)

Fig. 6

Percent change in LV electrical asynchrony during epicardial versus endocardial CRT as a function of the ratio of outer LV radius to inner LV radius in the three experimental groups. P values signify a statistical significant difference in ENDO-EPI CRT between groups

Fig. 7

Examples of echocardiography, fluoroscopy, and cardiac MRI in canine hearts before and after creation of mitral regurgitation. The cardiac MRI was performed 5 months after creating mitral regurgitation. Arrows point to the regurgitative blood flow into the left atrium

Fig. 8

Bi-weekly echocardiographic follow-up of left ventricular internal diameters of a dog with mitral regurgitation at week −4. At day 0, the left bundle branch is ablated. Note the steep increase in end-diastolic and end-systolic internal diameter of the left ventricle after superimposing LBBB upon mitral regurgitation