Regional myocardial mechanics: there’s more than meets the strain

This editorial refers to ‘Acute redistribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling’, by J. Duchenne et al., pp. 619–628. In the present issue of the Journal, Duchenne et al.1 present the results of a multicentric study relating the response to cardiac resynchronization therapy (CRT) to the homogenization of ventricular myocardial work achieved acutely by the device. The study is an encouraging example of the potential of academically developed technologies designed to complement more established methods provided by the imaging industry. Assessment of left ventricular regional mechanics has been of paramount interest for clinicians and researchers since the beginnings of cardiac imaging. For decades, eyeball assessment of wall motion has been the cornerstone method for addressing regional ventricular function and, in good hands, still has priceless value in modern cardiovascular medicine.2 In the late 90s, post-processing developments enabled obtaining indices of myocardial deformation previously reserved to invasive sonomicrometric experiments or complex tagging magnetic resonance sequences. This opportunity for measuring myocardial strain opened a whole new world in the analysis of cardiac function. In continuum mechanics, strain accounts for the relative deformation of a body. Current methods for measuring myocardial strain, are based on tracking image features along the cardiac cycle at high temporal and spatial resolutions.3,4 Early adopted by most ultrasound vendors, strain soon became the basis of hundreds of studies flooding the imaging literature. The clinical potential of strain to detect subtle myocardial abnormalities in almost all cardiac diseases previously known5 or unknown6 to impact regional function is only beginning to be exploited.3 However, the fact that strain shows only a partial picture of regional mechanics should not be overlooked. Myocardial strain results from the complex interplay among multiple forces acting and counteracting on each element of tissue (see Figure 1). During systole, a dramatic increase in elastance rapidly shortens and thickens the myocardium (typically characterized as negative longitudinal strain). Therefore, the major contributor of myocardial systolic strain is contractility—the intrinsic capacity of the myocyte to generate force. Additional factors such as the degree of sarcomere diastolic pre-stretching and local sympathetic activation (via modulation of cytosolic calcium concentration) also modulate systolic strain. Main factors involved in the regional stress–strain relationship of the myocardium. Main factors involved in the regional stress–strain relationship of the myocardium. Body deformation always needs to be interpreted in the light of the undergoing stresses that are acting on it. In fact, the relationship between these two magnitudes is basic to understand the mechanical properties of any material. Stress designates the internal forces that neighbouring particles exert on each other. In the myocardium, a first source of internal stress is caused by the conformational changes of its non-contracting structural elements. Whenever the myocardium contracts beyond its equilibrium state, the compression of titin and the extracellular matrix build an intrinsic restoring elastic stress that favours relengthening.7As filling evolves, these same elements become stretched and now the intrinsic stress changes sign, favouring re-shortening. These expansion/compression stresses of non-contractile elements play a major role in diastolic function and dysfunction. However, the main source of myocardial stress is related to transmural pressure. Chamber pressure acts directly on the endocardium as a compression force and, in general, the counter pressure on the other side of the myocardial wall is usually considered negligible except for the septum and the right ventricle.8 According to Laplace’s law, external systolic stress depends directly on transmural pressure and wall curvature (that determines the resultant of pressure forces in each element of the muscle) and inversely on regional thickness (how much tissue material is subjected to the pressure forces). Therefore, at identical levels of contractility, radial strain will be lower in flatter or thinner myocardial walls or dealing with higher regional pressures. Stress and strain are highly anisotropic in the myocardium due to the oblique 3D alignment of myocardial fibres. Therefore, although most relevant myocardial stresses take place as compression/expansion forces, torsion (between the apex and the base), and shear (between layers within the myocardium) also condition ventricular mechanics. For this reason, the usual simplification of the full 3D co-ordinate system into only the longitudinal, circumferential, and transversal projections may entail an important loss of information. Sarcomere force, elastic myocardial properties, intraventricular pressure, myocardial curvature, and wall thickness all undergo dynamic changes during the cardiac cycle. Consequently, both strain and stress are time-dependent magnitudes and very rich information on regional mechanics can be obtained by plotting regional stress vs. strain in a phase diagram (Figure 2). In the in vivo healthy myocardium, the stress–strain relationship follows a counterclockwise loop during the cardiac cycle. The area inside the loop represents the ability of the myocardial region to absorb or deliver energy (‘work’). Myocardial work is closely related to myocardial energy consumption (e.g. as measured as local oxygen uptake) and the relationship between these two variables defines myocardial efficciency.10 Stress–strain myocardial loops of lateral wall (red) and septum (blue) in the case of 150 ms delayed contraction of the lateral wall (left) and synchronous contraction between the septum and lateral wall (right). Notice the clockwise direction of the septum loop during systole in the first case: instead of releasing energy to the flow, it is absorbing it (negative W). Numbers account for the cardiac phases as defined from left ventricular inflow and outflow signals. 1: filling; 2: isovolumic contraction; 3: ejection; 4: isovolumic relaxation. Computer-generated data.9 Stress–strain myocardial loops of lateral wall (red) and septum (blue) in the case of 150 ms delayed contraction of the lateral wall (left) and synchronous contraction between the septum and lateral wall (right). Notice the clockwise direction of the septum loop during systole in the first case: instead of releasing energy to the flow, it is absorbing it (negative W). Numbers account for the cardiac phases as defined from left ventricular inflow and outflow signals. 1: filling; 2: isovolumic contraction; 3: ejection; 4: isovolumic relaxation. Computer-generated data.9 The regional stress–strain loop is particularly well-suited to address the mechanical consequences of asynchrony.11 In advanced left bundle branch block, contraction of the septum takes place with limited chamber pressurization because the lateral wall is fully relaxed. Hence, as the lateral wall contracts and the left ventricular pressure reaches its peak, the septum is already relaxing; subsequent septal bulging absorbs and wastes a great amount of systolic work. Thus, asynchrony induces large heterogeneity between the work performed by the septum (negative) and the lateral wall (positive) impairing pumping efficiency. In their study, Duchenne et al.1 address the potential of regional work analysis to understand the benefit of CRT. This approach is not novel, as it based on previous work using invasive measurements of regional work.12 Instead, Duchenne et al. use a fully non-invasive method to calculate regional work based on an estimation of intraventricular pressure.13 The authors elegantly demonstrate that the amount of reverse remodelling achieved by CRT in the long-term best correlates with the amount of homogenization of the regional work, induced acutely after device implantation. Therefore, work homogenization between the septum and the lateral wall is necessary to obtain a global benefit of CRT. A number of limitations of their study need to be taken into account. First, the impact of imputing the diastolic intraventricular pressure waveform and neglecting regional pressure differences14 on work calculations is unknown. Instantaneous local curvature changes may be also relevant in remodelled or overloaded regions. Furthermore, in clinical terms, the impact of their findings seems limited as it can only be calculated after CRT implantation. Thus, the potential benefit of analysing regional work for preselecting candidates is still incompletely addressed and more clinical studies are warranted. Also, in terms of predicting reverse remodelling, the net improvement of regional work analysis over conventional strain temporal homogenization was relatively modest (R = 0.62 vs. R = 0.55, respectively). The study by Duchenne et al. is sound because it exploits the fully non-invasive analysis of regional mechanics in the clinical setting. It shows there is still a huge potential for technical improvements in cardiac ultrasound by assessing regional phenomena. In the current era of imaging research, highly devoted to artificial intelligence heuristic—and frequently blind—developments, the strategy of implementing well-known physiological foundations to improve our understanding of cardiac diseases and therapies is particularly welcome. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal - Cardiovascular Imaging or of the European Society of Cardiology.