Non-linearity of end-systolic pressure–volume relation in afterload increases is caused by an overlay of shortening deactivation and the Frank–Starling mechanism

The linearity and load insensitivity of the end-systolic pressure–volume-relationship (ESPVR), a parameter that describes the ventricular contractile state, are controversial. We hypothesize that linearity is influenced by a variable overlay of the intrinsic mechanism of autoregulation to afterload (shortening deactivation) and preload (Frank-Starling mechanism). To study the effect of different short-term loading alterations on the shape of the ESPVR, experiments on twenty-four healthy pigs were executed. Preload reductions, afterload increases and preload reductions while the afterload level was increased were performed. The ESPVR was described either by a linear or a bilinear regression through the end-systolic pressure volume (ES-PV) points. Increases in afterload caused a biphasic course of the ES-PV points, which led to a better fit of the bilinear ESPVRs (r2 0.929 linear ESPVR vs. r2 0.96 and 0.943 bilinear ESPVR). ES-PV points of a preload reduction on a normal and augmented afterload level could be well described by a linear regression (r2 0.974 linear ESPVR vs. r2 0.976 and 0.975 bilinear ESPVR). The intercept of the second ESPVR (V0) but not the slope demonstrated a significant linear correlation with the reached afterload level (effective arterial elastance Ea). Thus, the early response to load could be described by the fixed slope of the ESPVR and variable V0, which was determined by the actual afterload. The ESPVR is only apparently nonlinear, as its course over several heartbeats was affected by an overlay of SDA and FSM. These findings could be easily transferred to cardiovascular simulation models to improve their accuracy.

The Arrival of Information and Price Adjustment Across Extreme Quantiles: Global Evidence

This study investigates the impact of information arrival on prices for 21 major global market indices for the period 1998–2018, employing quantile regression methodology. The results show that there is a contemporaneous and causal effect of volume on returns. This return-volume relation is a manifestation of systematic market-wide information that is released in an autocorrelated manner to market participants. This information is absorbed by the market participants over short horizons, within a day. This leads to uniform expectations and, in turn, lower volatility levels. The effect of volume on return is heterogeneous across the conditional quantiles, reflecting the contrasting patterns in the transmission of positive and negative news. This evidence is more pronounced when the intensity of information arrival is high (the tails of return distribution), which is consistent with the mixture of distribution hypothesis and information asymmetry hypothesis.

Hemodynamic Effects of Alpha-Tropomyosin Mutations Associated with Inherited Cardiomyopathies: Multiscale Simulation

The effects of two cardiomyopathy-associated mutations in regulatory sarcomere protein tropomyosin (Tpm) on heart function were studied with a new multiscale model of the cardiovascular system (CVS). They were a Tpm mutation, Ile284Val, associated with hypertrophic cardiomyopathy (HCM), and an Asp230Asn one associated with dilated cardiomyopathy (DCM). When the molecular and cell-level changes in the Ca2+ regulation of cardiac muscle caused by these mutations were introduced into the myocardial model of the left ventricle (LV) while the LV shape remained the same as in the model of the normal heart, the cardiac output and arterial blood pressure reduced. Simulations of LV hypertrophy in the case of the Ile284Val mutation and LV dilatation in the case of the Asp230Asn mutation demonstrated that the LV remodeling partially recovered the stroke volume and arterial blood pressure, confirming that both hypertrophy and dilatation help to preserve the LV function. The possible effects of changes in passive myocardial stiffness in the model according to data reported for HCM and DCM hearts were also simulated. The results of the simulations showed that the end-systolic pressure–volume relation that is often used to characterize heart contractility strongly depends on heart geometry and cannot be used as a characteristic of myocardial contractility.

Ejection Fraction and Espvr: A Study in the Mechanics of Left Ventricular Contraction

The end-systolic pressure-volume relation (ESPVR) is the relation between pressure Pm and volume Vm in the heart left ventricle when the myocardium reaches its maximum state of activation during contraction near end-systole. Relations between the ejection fraction (EF), parameters describing the ESPVR and the areas under the ESPVR are derived in this study for a linear model of the ESPVR. An important feature of the model is the inclusion of the active pressure generated by the myocardium during an ejecting contraction (also called isovolumic pressure Piso) in the mathematical expression of the linear ESPVR. Criteria that can help in understanding the problem of heart failure with normal or preserved ejection fraction (HFpEF) are discussed. Applications to clinical data published in the literature are presented, the applications show the consistency of the mathematical formalism used. When ratios of pressures are used, the calculation can be carried out with clinical data measured in a non-invasive way (the ratio of pressures can be calculated). This study shows that the EF is just one index of several indexes that can be derived from the ESPVR for the assessment of the ventricular function, and that using bivariate (or multivariate) analysis of data is superior to univariate analysis for the purpose of classification and segregation between different clinical groups.

1177 The additive prognostic value of end-systolic pressure-volume relation by CMR in patients with with known or suspected coronary artery disease

Background The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. This index is easily obtained during routine stress echocardiography but can be derived also during a stress cardiovascular magnetic resonance (CMR) exam, that is the gold standard for the quantification of biventricular volumes. Purpose The aim of this study was to assess for the first time the prognostic value ofdelta rest-stress ESPVR (DESPVR) by dipyridamole stress-CMR in patients with known or suspected coronary artery disease (CAD). Methods One hundred and sixty-six consecutive patients (37 females, main age 61.96 ± 10.05 years) who underwent dipyridamole stress-CMR in a high volume CMR Laboratory were considered. Abnormal wall motion and perfusion at rest and after dipyridamole were analysed. Macroscopic myocardial fibrosis was detected by the late gadolinium enhancement (LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson method. Results An abnormal stress CMR was found in 39 (23.5%) patients; 24 patients had a reversible stress perfusion defect in at least one myocardial segment and 15 a reversible stress perfusion defect plus worsening of stress wall motion in comparison with rest. Myocardial fibrosis was detected in 69 patients (41.6%). A DESPVR < 0.009 was detected in 74 patients (44.6%). During a median follow up of 55.51 months (IQ range 33.20 months), 54 patients (32.5%) experienced major cardiac events: 5 deaths, 2 ventricular arrhythmias, 18 coronary syndromes, and 29 heart failure hospitalization.Reversible perfusion deficit, DESPVR < 0.009, diabetes and family history were significant univariate prognosticators. In the multivariate analysisthe independent predictive factors were reversible perfusion deficit (hazard ratio-HR = 2.17, P = 0.010), DESPVR < 0.009 (HR = 1.92, P = 0.028) and diabetes (HR = 2.42, P = 0.004). The Kaplan–Meier curve for DESPVR is shown in Figure 1. The log-rank test revealed a significant difference (P = 0.003). Conclusions DESPRV assessed by CMR provides a prognostic stratification in patients with known or suspected coronary artery disease, in addition to that supplied by reversible perfusion deficit and diabetes. Abstract 1177 Figure 1

Effect of sampling conditions on the results of the Radon-222 specific activity analysis in drinking water with Gamma/spectrometry

The article deals with researches of the different factors’ impact upon the result of gamma/spectrometric determination of 222Rn specific activity in drinking water during sampling. We determined the impact of the air presence in a sampler, pH of water and temperature regime of the sample storage. We have shown that occasional ingress of air in a sampler considerably (two and more times) decreases the analysis results. The observed dependence of the resu lt decrease (in comparison with the reference sample) on the air volume to water volume relation in the sample is close to the logarithmic dependence. Thus, the 40 ml volume of air in a two-liter sampler gave approximately 10 % lower result of the radon determination in comparison with that in the reference sample. At the same time, the sample acidulation with nitric acid to pH = 1,2–2,5 and a sample single frosting/defrosting cycle did not result in statistically reliable distinction of the result from that of the reference sample.

Synergistic Model of Cardiac Function with a Heart Assist Device

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. The left ventricular pressure–volume relation plays a key role in the diagnosis and treatment of heart diseases. Lumped-parameter models combined with pressure–volume loop analysis are very effective in simulating clinical scenarios with a view to treatment optimization and outcome prediction. Unfortunately, often invoked in this analysis is the traditional, time-varying elastance concept, in which the ratio of the ventricular pressure to its volume is prescribed by a periodic function of time, instead of being calculated consistently according to the change in feedback mechanisms (e.g., the lack or breakdown of self-organization) in heart diseases. Therefore, the application of the time-varying elastance for the analysis of left ventricular assist device (LVAD)–heart interactions has been questioned. We propose a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating the mechanical, electric, and chemical activity on microscale sarcomere and macroscale heart levels and investigating the effect of an axial rotary pump on a failing heart. We show that our synergistic model works better than the time-varying elastance model in reproducing LVAD–heart interactions with sufficient accuracy to describe the left ventricular pressure–volume relation.