Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

The general purpose of this thesis is to establish the ability of Speckle Tracking Echocardiography (STE) in assessing left atrial (LA) response to pressure and volume overload respectively in aortic stenosis (AS) and mitral regurgitation (MR), and to evaluate its accuracy in predicting LA and right ventricular (RV) fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx). I demonstrated that assessment of left ventricular (LV) long axis systolic velocity and amplitude of excursion is more sensitive than simple determination of ejection fraction (EF) for revealing the beneficial impact of MR surgery on overall LV systolic performance. Severe symptomatic AS is associated with LA enlargement and compromised mechanical function with a high incidence of peri-operative atrial fibrillation (AF). Valve replacement reverses these abnormalities and regains normal atrial function, a behaviour which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size and function disturbances, as shown by myocardial strain measurements might contribute to better patient’s recruitment for a safe valve replacement. In late stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate function measure that correlates with the extent of RV myocardial fibrosis and functional capacity. In patients with preserved EF, severe MR masks LV and LA myocardial dysfunction and correlates with symptoms and post-operative cavity function instability. Three months after MVR, the underlying myocardial disturbances are unmasked suggesting that most pre-operative measurements are subject to loading conditions. Finally LA volume and PALS remain the main predictors of post-operative AF, thus should be used for stratifying surgical risk. STE has been shown to accurately determine the severity of impairment of LA myocardial function shown by suppressed PALS which was the strongest predictor of the presence and extent of fibrosis, over and above other structure and function parameters. These findings may assist in better stratifying patients with end stage HF and identifying particularly those requiring HTx.

The general purpose of this thesis is to establish capability and accuracy of speckle tracking echocardiography (STE) in assessing left atrial (LA), left ventricular (LV) and right ventricular (RV) function and their correlation with myocardial fibrosis, filling pressure and clinical outcomes in advanced heart failure (HF) patients before and after heart transplantation (HT). I demonstrated that HT recipients had impaired LV twist dynamics in the form of reduced rotation twist angle and untwist rate but time to peak twist was not different from the age matched controls and other cardiac surgical patients. With a longitudinal study conducted on patients with refractory HF, the best prognostic power has been shown by RV strain analysis. Among the indexes of LV function, the LV ejection fraction (LVEF) demonstrated the lowest diagnostic accuracy; instead LV global circumferential strain (GCS) showed a better sensitivity and specificity than LV global longitudinal strain (GLS). When analyzing the relationship between different severity of myocardial fibrosis and LV cavity function, the strongest function parameter that correlated with severity of myocardial fibrosis was GLS. In contrast, none of diastolic LV function or even measures of exercise capacity correlated with myocardial fibrosis. In patients with end-stage HF, global peak atrial longitudinal strain (PALS), an index of atrial reservoir function was dependent by pulmonary capillary wedge pressure (PCWP) and LV fibrosis, but not influenced by LV systolic function. Results from this study confirm previous evidence of correlation between impaired global PALS and increased PCWP.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.