This study was an attempt to test the clinical feasibility of the state diagram as a visualization tool for cardiac mechanics. The state diagram was designed to present the mechanics of both the left and the right side of the heart since they each have an AV-piston. The myocardium is the power source for the pumping function. It has a flexible structure with a constant volume, which means that generation and release of tension forces within the myocardium can occur with low or no external volume changes, i.e. changes of the epicardial borders [
16]. The myocardium has to build up enough tension before there can be any flow out of the ventricle and must then release this tension before the filling of the ventricles can occur. The global function of the heart, represented by the global state diagram, results in flow and pressures into and out of the right and left side of the heart. The global function is dependent on many complex regional functions and external conditions. The fact that the heart has to build up and release enough tension before there can be any large flow or pressure changes partly explains why there is a time delay between different regional muscular movements and global events. The regional velocity curves can either be an active movement contributing to the global function or passive, i.e. as a result of movements occurring at other sites in the heart. In this way the velocity curves contain both events useful to generate the global state diagram from the right and left ventricles and events to create local state diagrams that depict the local functions at different sites of the two ventricles.
The phases in the state diagram have been defined in accordance with the DDP-principle in order to illustrate the mechanics of the heart, and henceforth the heart will be described as a DDP. Since the motion of the AV-pistons largely represents the mechanics of the heart, the myocardial velocities were chosen to be measured in the basal segments of the heart, near the AV-pistons. The crucial task for the heart is to preserve flow and muscle dynamics throughout the cardiac cycle and to keep a constant inflow to the heart when the AV-pistons have to be accelerated, retarded and change direction. The more or less constant inflow to the heart is achieved by suction of blood into the atria during Ventricular Ejection and continuous need of further inflow during the hydraulic return of the AV-piston during Rapid and Slow Filling.
Motion shifts of the piston associated with opening and closing of the valves are critical events that affect the performance of the heart. These events have in this study been included in the phases Pre-Ejection and Post-Ejection, names which refer to their close link to the beginning and ending of Ventricular Ejection. Pre-Ejection and Post-Ejection differ from the traditionally defined isovolumic phases by including volume redistributions between the atria, the ventricles and its outlets. During Atrial Contraction, the AV-pistons are drawn towards the inlet areas of the atria, the base of the heart, whereas during Pre-Ejection they are drawn towards the apex of the heart [
17,
18]. This will result in rearrangement of blood volumes from the atria to the ventricles during Atrial Contraction and in the reverse direction during Pre-Ejection. In this way the stroke-length of the AV-pistons can increase and the closure of the tricuspid and mitral valves can occur with small disturbances in the inflow to the heart.
Events connected to Pre-Ejection and Post-Ejection are considered to result from pre- and postsystolic reshaping of the muscles in the ventricles [
19]. Pre-Ejection was defined starting with the beginning of the closure of the tricuspid and the mitral valves, i.e. the generation of muscle tension and blood volume redistributions. This phase ends with a powerful tension increase that initiates the opening of the pulmonic and aortic valves. Observe that the flow out of the valves does not occur at this time point but in early Ventricular Ejection. Post-Ejection starts when the pulmonic and aortic valves are about to close, just before a backflow into the ventricles is generated. The forces of the backflow overcome the tension in the muscles and the ventricular volumes increase. This phase ends when the rapid relaxation starts and the tricuspid and the mitral valve are about to open, i.e. the muscle tension decreases which enables the returning action of the AV-pistons. This means that the flow over the tricuspid and mitral valves starts first during early Rapid Filling. Pre-Ejection, Ventricular Ejection and Post-Ejection in the regional and global state diagrams are according to these definitions different to what is commonly used when describing the isovolumic contraction and relaxation phases and the ejection. The phases Ventricular Ejection, Rapid Filling and Atrial Contraction were divided into subphases to improve the diagnostic power of the state diagram, as these subphases can provide further visual information concerning contractility of the heart muscles and flow and pressure conditions in the heart and its inlets and outlets.
Clinical feasibility
The results of this study show that the state diagram has potential to be used for visualization of various cardiac dysfunctions. It also demonstrates the state diagram to be a more sensitive tool for detection of NSTEMI compared to other established echocardiographic variables such as E/E' ratio, LVEF and WMSI, since no significant differences were found in these variables. Moreover, it must be considered that the state diagram method had the ability to separate the groups, even though the control group demonstrated some clinical features. The novelty with this method is the visualization by presenting a clear overview of cardiac mechanics according to the DDP-principle. With this approach it is possible to create a state diagram, which allows for evaluation of parallel information by displaying the relationships between different phases in the cardiac cycle.
Though the state diagram method is based on TDI, its accuracy and reproducibility can be compared with the accuracy and the reproducibility established for TDI. TDI has been validated and a reasonably good reproducibility has been found [
20,
21]. However, the accuracy and reproducibility of the state diagram method has to be further addressed in future studies. Additionally, in comparison with methods quantifying cardiac function through single amplitude values of e.g. displacement, velocity and strain, the timing information used in the state diagram would most likely be less sensitive to noise, angular errors and filtering effects. The state diagram as a diagnostic tool could presumably be improved in future versions by extending it to contain information about, for example, stroke-length, auto-regulating functions of IVS [
15], flows and pressures.
The pre- and postsystolic phases, called Pre-Ejection and Post-Ejection in this study, are important considerations when evaluating cardiac function and the prolongation of these time intervals are associated with systolic and diastolic ventricular dysfunction [
22‐
24]. The results of the clinical study showed significantly prolonged Pre-Ejection and Post-Ejection for the NSTEMI subjects compared to the control subjects (p < 0.05), which has been quantitatively and fractionally presented in the state diagram in Figure
4. This is also clearly seen in the clinical examples in Figure
3, when comparing the Pre-Ejection and Post-Ejection for the healthy subject and the athlete with the diseased ones. One reason behind the short Post-Ejection phase noticed in the athlete in Figure
3b could be that an athlete has high persisting flow in the outflow vessels towards the end of Ventricular Ejection, which will reduce the pressure inside the ventricles, and thus the tension in the ventricular muscles, thereby shortening Post-Ejection. These dynamic features are also observed in the DDP and, in general shorter Pre-Ejection and Post-Ejection improve the dynamics in the heart, which could be an explanation for the improved ejection fraction seen in well-trained athletes [
25].
Furthermore, the clinical examples of the ischemic and the dyssynchronic subjects indicate that the state diagram can detect and display regional heart muscle disturbances such as infarcted and ischemic movement patterns and dyskinetic functions of the muscle cells. Ventricular dyssynchrony disturbs the synchronous pumping and relaxation function of the heart leading to a reduced diastolic filling time and a post-systolic regional contraction [
26], two factors that are easily detected in the state diagram. Coronary blood flow is impeded during systole which makes the duration of diastole an important determinant of myocardial perfusion. Adjustment of the diastolic time fraction has been proposed as a protective intervention to preserve coronary blood flow [
27]. In left ventricular dyssynchrony, the regions with a dyssynchronic contracting myocardium pattern can be identified and the obtained information could potentially improve the selection of patients referred to cardiac resynchronization therapy. The state diagram acquired in the subject with dyssynchrony, Figure
3d, clearly visualizes how regional functions create impacts on all the phases in the global state diagram. A prolonged Post-Ejection, usually referred to as diastolic dysfunction in individuals with dyssynchroni disorders [
28], can by visualization with the state diagram, be proven to originate from dyssynchrony occurring before this phase. Another reason for the prolonged Post-Ejection seen in the dyssyncronic subject, the ischemic subject and the NSTEMI-group could be low flow and high pressures in the outflow vessels towards the end of Ventricular Ejection, which would sustain the tension in the ventricular muscles and prolong the Post-Ejection. The significant difference between the groups found in late Atrial Contraction and early Rapid Filling indicates that muscular tension patterns differ between the groups. Indeed, previous studies have shown that degeneration of the elastic properties of the ventricles provokes a restrictive ventricular filling pattern characterized by a shortened early diastolic mitral flow deceleration time [
29]. The corresponding time in the myocardial velocity curve is visualized in the state diagrams, giving an impression of the receiving performance of the ventricles. In cases with normal right atrial pressure, pulmonary artery systolic pressure (PASP) has been shown to correlate well with IVRT measured in the right ventricular free wall [
30]. That IVRT is sensitive to changes in PASP should be considered when evaluating the right ventricular information in the state diagram.
Limitations
Care must be taken when interpreting the results since the number of patients included in the study was small. The state diagrams for the patients in the clinical study and for the ischemic clinical example were generated using a 2D transducer. A 2D transducer renders the state diagrams dependent on recording conditions since the timing, based on velocities from different cardiac cycles, is displayed simultaneously. This is negligible in most cases since the beat-to-beat differences during an examination are small. In addition, the differences in heart rate between each NSTEMI patient and the matched control might have affected the results of the clinical study. However, these differences were not systematic and had most likely only a moderate influence on the results.