General objectives

1. Diastolic dysfunction: Left ventricular function has traditionally been evaluated non-invasively in terms of ejection fraction (LVEF). The assessment of LVEF is important for diagnostics, prognosis and selection of treatment. Many patients with symptoms of heart failure have, however, normal ejection fraction and appear to have diastolic heart failure. In this patient group there is need for other measures than ejection fraction. We are studying LV diastolic lengthening rate and LV untwisting rate and how these indices may be used as markers of LV diastolic dysfunction. In addition to experimental models we utilize mathematical heart modeling to explore our ideas. This includes finite element simulation to interpret measurements of myocardial wall deformation under normal and diseased conditions. The recently introduced method speckle tracking echocardiography (STE) represents a simplified, objective and angle-independent modality for quantification of regional myocardial deformation. The software utilizes conventional grayscale B-mode recordings, and tracks myocardial speckles which serve as natural acoustic markers. Radial and longitudinal myocardial deformation can be measured simultaneously from long-axis recordings, radial and circumferential deformation from short-axis recordings and LV torsion from assessment of apical and basal short-axis rotation (Fig. 1).

Fig 1: Representative echocardiographic apical 2-chamber and apical short axis images (Left). Speckle tracking was applied on the images through the cardiac cycle to assess myocardial deformation: Longitudinal strain (A) was assessed from the long-axis view, circumferential strain (B) and radial strain (C) were assessed in the short axis view. Representative strain curves are displayed (Right). Peak systolic strain are indicated with white squares. O Gjesdal.

The systolic torsion (twisting motion) of the left ventricle (LV) and the subsequent untwisting during diastole appears to play a crucial role in LV ejection and filling. During the cardiac cycle, there is a systolic twist and an early diastolic untwist of the LV about its long axis because of oppositely directed apical and basal rotations. A non-invasive echocardiographic method for quantification of LV rotation and torsion was introduced, i.e. speckle tracking echocardiography. When validated against implanted ultrasonic crystals in an animal model and against tagged MRI in humans, the method demonstrated ability to quantify LV torsion. Measurements of LV torsion might be an important diagnostic tool in ischemic heart disease, for diastolic function and in LV hypertrophy.

2. Coronary artery occlusion: Although acute myocardial infarction is treated preferably by early percutaneous coronary intervention (PCI), there is limited access to this treatment, and a large fraction of patients receive intravenous thrombolytic as primary treatment. These patients are referred for “rescue PCI” only when there is no reperfusion after thrombolytic treatment. The main problems with the latter strategy are that all myocardium at risk may have undergone necrosis and therefore PCI is unnecessary. Furthermore, we lack reliable methods to determine if reperfusion has been achieved by the thrombolytic. One of our main objectives is to develop better functional imaging in order to differentiate between viable and necrotic myocardium and to determine when reperfusion has been achieved

3. LV dyssynchrony: Quite recently cardiac resynchronisation therapy (CRT) has been documented to be a powerful treatment in patients with severe congestive heart failure, causing reverse LV remodelling, improvement of symptoms and reduction of mortality. The principle of CRT is that patients with ventricular dyssynchrony can be resynchronised and contractile function improved by bi-ventricular pacing. Presently, patients are selected for CRT on basis of ECG with wide QRS. However, in about 30 % of patients who are selected for CRT on basis of QRS criteria, there is no improvement in symptoms, and in some cases aggravation of symptoms. Therefore, a major problem with CRT is that many patients are non-responders, and we need better criteria for selection of candidates for this treatment modality. Because ECG has limited ability to identify candidates for CRT, echocardiography with tissue Doppler imaging has been proposed as a more sensitive and more specific method to identify dyssynchrony. However, so far echocardiography has no proven clinical value in selection of candidates for bi-ventricular pacing. In particular, it has been confusing that many patients with a narrow QRS have dyssynchrony by echocardiographic criteria. We suggest that LV dyssynchrony in heart failure patients with narrow QRS may be due to abnormal loading conditions, and therefore do not represent an “electrical problem”, and should not be treated by bi-ventricular pacing. We investigate the hypothesis that LV dyssynchrony may be caused by abnormal cardiac loading conditions in the presence of normal electrical conduction.

4. LV mechanical-electrical interactions: Evaluating patients with susceptibility for cardiac arrhythmias and sudden cardiac death is a major challenge in daily cardiology practice. Electrophysiological studies have demonstrated that damaged myocardium (e.g. infarcted or genetically altered) provides the substrate for malignant arrhythmias. Echocardiographic techniques can accurately quantify regional myocardial function. There is limited insight into how regional mechanical dysfunction may modify risk for ventricular arrhythmias. We investigate if dispersion of LV myocardial function may have an impact on risk for ventricular arrhythmias (Fig 2).

Fig 2. This figure demonstrates mechanical dispersion in a patient with malignant arrhytmia.