Instant contractility, just apply a single beat

Quantification of left ventricular (LV) systolic function is one of the most common evaluations performed in cardiac research studies. Indices such as ejection fraction, stroke work and peak derivative of the pressure (dP/dtmax) are frequently used, but all these are highly load dependent. Gold-standard indices of systolic contractile function that are less load dependent are end-systolic elastance (Ees), preload-recruitable stroke work and the relationship between dP/dtmax and end-diastolic volume (EDV). However, obtaining these is complicated. Simultaneous recordings of pressure and volume during a loading intervention, typically a transient occlusion of the vena cava, are needed. This requires additional instrumentation; performing caval occlusion is associated with some risks, and acquisition of reliable measurements is complicated. It can be particularly challenging to obtain good volume measurements. Conductance catheter volumemeasurements are prone to several sources of error; volume calculation from sonomicrometric crystals can be considered to have poor spatial resolution because it is based on multiplication of three diameters, vulnerable to regional motion abnormalities and dependent on crystal placement; imaging requires segmentation and has challenges with reproducibility. Furthermore, the interpretation of the measurements is sometimes also complicated, as reviewed nicely by Burkhoff et al. (2005). Thus, the problems in obtaining these gold-standard indices result in their rather limited use. There is, therefore, a great demand for simpler indices of contractile function. Over the years, several single-beat contractility indices have been suggested. Typically, such an index has initially been proposed and tested in a small study of one species, with a limited number of interventions. Subsequent studies have then verified and tested other aspects of the index, contributing to the collective evidence of its general validity. However, in this issue of the Journal, Ahmadian et al. (2022) present a large and comprehensive study of the performance of 12 single-beat contractility indices, aiming to test their general validity. The indices were examined in eight different experiments in rodents, porcines and canines to investigate whether they were correlated with the gold-standard indices from vena cava occlusions, whether theywere preload independent andwhether they showed the expected responses to pharmacologically or pathologically induced changes in contractile function. The authors found that the majority of the indices did not pass all tests and could not be considered valid in both rodents and large animal models. The three indices ESP/EDV, Pmax/EDV and (dP/dtmax)/EDV, in addition to the arterial pressure-based index ARTESP/EDV, were considered to pass all tests, where ESP is end-systolic pressure at the top left corner of the pressure–volume (PV) loop. The authors defined Pmax as peak pressure during ejection, which is a simplification compared with its originally more complex mathematical estimation of the maximal pressure a ventricle would generate during a pure isometrically contracting beat. Thus, this study tests not only previously published indices, but also the new ESP/EDV indices and the simplified Pmax/EDV. Of particular interest could be that two of these indices can be estimated non-invasively and thus have potential for use in clinical practice, because Pmax can be approximated as systolic cuff blood pressure (SBP), and ARTESP = 0.9 × SBP. Notably, all four ‘accepted’ indices were divided by EDV, which can be regarded as a preload adjustment. Such preload correction seems reasonable and would have been useful in our previous study, in which we observed that, in canines with left bundle branch block, cardiac resynchronization therapy acutely shifted the PV loop leftward, i.e. also reducing EDV (Boe et al., 2019). Although resynchronization improved systolic function, several of the systolic indices were not altered and thus did not show the improved function, because the increase in these parameters was masked by the preload-induced reduction. However, given that EDV was reduced, dividing by EDV would have demonstrated the improved systolic function. Additionally, we observed no change in Ees in that study, but the intercept of the Ees line with the volume axis (V0) was reduced, suggesting that contractile function was improved as the ventricle was able to contract to a lower volume at identical pressure. The latter point illustrates a challenge with interpreting the gold-standard contractility indices, because they consist of both a slope and an intercept. The extensive testing of the 12 selected simple single-beat contractility indices in the paper by Ahmadian et al. (2022) also serves as a convenient overview of these different indices, which might act to increase their use in more studies. Future studies will disclose more of the strengths and weaknesses of the single-beat indices. For example, it seems likely that ESP and Pmax will increase with an acute increase in afterload and, in that case, falsely indicate increased contractility. In the typical hypertensive heart failure with preserved ejection fraction patient with concentric hypertrophy, the indices will presumably also be increased, reflecting a change in chamber properties, but it is uncertain whether and how the muscle properties are affected, which would ideally require more complex investigation by stress–strain relationships (Burkhoff et al., 2005; Kawaguchi et al., 2005). Such chronic morphometric changes complicate interpretations even with the gold-standard contractility indices, but these methods can evaluate acute changes with a higher degree of certainty (Pacher et al., 2008). It will therefore be interesting to follow how the single-beat contractility indices are used in future studies and see the situations in which they can be most useful.