Ventricular Elastance Research Articles

Estimation of Left Ventricular End-Systolic Elastance From Brachial Pressure Waveform via Deep Learning.

Determination of left ventricular (LV) end-systolic elastance (E es ) is of utmost importance for assessing the cardiac systolic function and hemodynamical state in humans. Yet, the clinical use of E es is not established due to the invasive nature and high costs of the existing measuring techniques. The objective of this study is to introduce a method to assess cardiac contractility, using as a sole measurement an arterial blood pressure (BP) waveform. Particularly, we aim to provide evidence on the potential in using the morphology of the brachial BP waveform and its time derivative for predicting LV E es via convolution neural networks (CNNs). The requirement of a broad training dataset is addressed by the use of an in silico dataset (n = 3,748) which is generated by a validated one-dimensional mathematical model of the cardiovasculature. We evaluated two CNN configurations: 1) a one-channel CNN (CNN1) with only the raw brachial BP signal as an input, and 2) a two-channel CNN (CNN2) using as inputs both the brachial BP wave and its time derivative. Accurate predictions were yielded using both CNN configurations. For CNN1, Pearson’s correlation coefficient (r) and RMSE were equal to 0.86 and 0.27 mmHg/ml, respectively. The performance was found to be greatly improved for CNN2 (r = 0.97 and RMSE = 0.13 mmHg/ml). Moreover, all absolute errors from CNN2 were found to be less than 0.5 mmHg/ml. Importantly, the brachial BP wave appeared to be a promising source of information for estimating E es . Predictions were found to be in good agreement with the reference E es values over an extensive range of LV contractility values and loading conditions. Therefore, the proposed methodology could be easily transferred to the bedside and potentially facilitate the clinical use of E es for monitoring the contractile state of the heart in the real-life setting.

Physiologic cardiovascular studies in resuscitated normotensive septic shock with persistent hyperlactatemia.

Background: To study effects of increasing vasopressor dosage and fluid resuscitation on ventriculoarterial (VA) coupling and venous return (VR)-related parameters in resuscitated normotensive septic shock patients with persistent hyperlactatemia. Methods: We performed a prospective experimental study in patients with septic shock who was admitted to medical intensive care unit and still had hyperlactatemia even received initial resuscitation to maintain mean arterial pressure (MAP) >65 mmHg. All patients received incremental dose of norepinephrine (NE) to increased MAP, then NE was titrated to baseline dosage and waited for 15 mins, then fluid bolus was given. VA coupling-related parameters [arterial elastance (Ea), left ventricular end-systolic elastance (Ees), left ventricular stroke work (SW), potential energy (PE), stroke volume (SV), and Ea/Ees], and VR-related parameters [central venous pressure (CVP), mean systemic pressure analogue (Pmsa), venous return pressure (Pvr)] were measured at 4 time points including pre-increased NE phase, post-increased NE phase, pre-fluid bolus phase, and post-fluid bolus phase. Primary outcome was average of Ea/Ees. Secondary outcomes were differences in VA coupling-related parameters and VR-related parameters between pre- vs. post- interventions. Results: All 20 patients were normotensive [MAP 74 (66-80) mmHg] with elevated blood lactate [2.7 (2.4-3.6) mmol/L] at enrollment. Average Ea/Ees was 0.89 (0.61-1.16). Compared to pre-increased NE phase, post-increased NE phase had significantly higher MAP, CVP, SV, SW, PE, Pmsa, and Pvr. Likewise, compared to pre-fluid bolus phase, post-fluid bolus raised MAP, CVP, SV, Ees, SW, Pmsa, and Pvr significantly. No difference in Ea/Ees compared between before- vs. after- received both interventions. Conclusions: In resuscitated normotensive septic shock patients with persistent hyperlactatemia, we found an average Ea/Ees of 0.89. Increasing NE dosage or fluid bolus increased most of VA coupling-related parameters and VR-related parameters, but not Ea/Ees. Further large study is warranted to validate these findings.

Ventricular-arterial coupling in hypertensive patients after TAVR. It is not all about the valve

Abstract Background In severe aortic stenosis, the left ventricle faces the challenge of the valvular load and the arterial load caused by abnormalities in systemic arterial compliance and systemic vascular resistance. The aim of this study is to assess the effect of hypertension control on left ventricular performance in patients that underwent TAVR. Methods 68 consecutive patients who underwent TAVR were analyzed; all patients were evaluated to confirm severe aortic stenosis with transthoracic echo (TTE). Conventional echo parameters were assessed as well as left ventricular mechanics parameters and vascular parameters such as arterial elastance (Ea), ventricular elastance (Ees) and V/Ac; besides all patients underwent TTE prior to TAVR, at discharge and 90 days follow-up visit. Results Mean age was 82±5; mean aortic valve area was 0.69±0.19, mean left ventricular ejection fraction was 58.3±12.1 and mean ventricular-arterial coupling was 1.6±0.9. At 90 days follow up we observed a significant worsening in V/Ac in those patients with poor control of blood pressure (>140/90mmHg), (1.8±0.5 vs 2.1±0.3, p=0.03). Aortic impedance was significantly higher (4.4±1.4 vs 3.5±1.2, p=0.05); Ea and Ees were also significantly higher in hypertensive patients (2.3±0.8 vs 1.7±0.6, p=0.05) and (1.4±0.7 vs 0.9±0.6, p=0.01) respectively. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed a slightly reduction in hypertensive patients, although not statistically significant. Conclusions Control of blood pressure seems to be an important factor that contributes to a better or rather worse LV performance and could have a potential role in systolic function and clinical outcome of patients after TAVR. Funding Acknowledgement Type of funding sources: None.

Automated non-invasive pressure-volume loop analysis of cardiac aging in a large cohort of healthy community dwellers

Abstract Background/Introduction Pressure-volume loops (PVloops) provide a wealth of information on cardiac function that is not readily available from cardiac imaging alone. Methods To estimate left ventricular (LV) PVloops non-invasively have been available, but have so far not been used to interrogate ventricular function in large patient cohorts, due to the complexity of estimating PVloops. A new method was recently validated that construct PVloops non-invasively from cine cardiac magnetic resonance (CMR), based on the time-varying elastance model [1]. At the same time, we have validated a framework for automated, quality controlled analysis of cine CMR in large cohorts of patients/subjects [2]. Combining these two methods could automated PVloop estimation, enabling analysis of ventricular pressure-volume relationships in large study populations. Purpose Evaluate if CMR-based non-invasive PVloops can be used to interrogate the impact of cardiac ageing on LV function occurring in a large population of healthy community dwellers. Methods Non-invasive PVloops were calculated from a full cardiac cycle LV volume curve and brachial blood pressure data using a recently validated method based on the time-varying elastance model [1], in 7,650 healthy community dwellers from the UKBiobank population study. The LV volume curve was automatically obtained using our state-of-the-art, quality controlled deep learning (DL) based cine CMR analysis framework [2]. External Work, pressure-volume-area (PVA), end-systolic pressure (Pes), ventricular elastance (Ees, an estimate of contractility) and arterial elastance (Ea) and energy per ejected volume (EEV: PVA/ stroke volume) were calculated from the PVloops. We performed univariate regression between PVloop parameters and age. We also calculated the additional impact of cardiovascular risk-factors in a multivariate analysis. Results See results in table 1. With age, LV volumes fall (p<0.001) in healthy subjects, while systolic blood pressure and Pes increases (both p<0.001). As a result of the higher afterload, PVA (p=0.894) and EW (p=0.499) do not significantly change with age despite a lower SV. Arterial elastance (Ea) increased, and so did contractility, as measured by Ees (p<0.001). Due to all these changes, EEV increased with age (p<0.001). In multivariate analysis, cardiovascular risk factors hypercholesterolemia and hypertension negatively impacted Pes, PVA, Ees and EEV. Diabetes and smoking habits did not. Conclusion Non-invasive CMR-based PVloop analyses capture the impact of known changes occurring during cardiac ageing on cardiac work, contractility and energetic expenditure. Obtaining PVloops automatically using our AI analysis system in this large cohort of healthy subjects allows to formulate reference for assessment of cardiac disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The authors acknowledge financial support (support) the National Institute for Health Research (NIHR) Cardiovascular MedTech Co-operative (previously existing as the Cardiovascular Healthcare Technology Co-operative 2012 - 2017) award to the Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and the NIHR comprehensive Biomedical Research Centre of the Guy's & St Thomas' NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health Univariate regression analysisExample of estimated PV loop

The state of the left ventricular-arterial coupling depending on the left ventricular ejection fraction in patients with acute myocardial infarction

Abstract Objective To conduct a comparative analysis of the indicators of left ventricular-arterial coupling (LVAC) in patients with primary acute myocardial infarction with ST segment elevation (STEMI), depending on the initial level of the left ventricular ejection fraction (EF). Methods The study included 148 patients with STEMI (mean age 51.5 [CI% 50.1; 52.9] years) in the first 24–96 hours from the disease onset. An inclusion criterion was the presence of hemodynamically significant stenosis of only one coronary artery according to the coronary angiography results. On days 7–9th from the disease onset, the patients underwent standard echocardiography on the MyLab device (Esaote, Italy) with the determination of the end diastolic volume (EDV), end systolic volume (ESV), EF and the subsequent calculation of LVAC: arterial elastance (Ea), left ventricular elastance (Ees), including those reduced to body surface area (Ea/BSA and Ees/BSA), LVAC index (Ea/ Ees). In accordance with the LVEF values, the patients were divided into 3 groups. The 1st group included 79 people with preserved EF (≥50%), the 2nd group – 53 patients with mid-range EF (40–49%); Group 3 consisted of 16 patients with reduced EF (<40%). The compared groups were matched by age, sex, anthropometric data, and treatment. Results In the 1st group, the Ea indicator was 1.8 [CI% 1.7; 1.9], in group 2 – 2.0 [CI% 1.8; 2.1], in the third group – 2.2 [CI% 1.9; 2.5] mm Hg/ml (p1-3 = 0.01). The Ees indicator in the comparison groups was 2.2 [CI% 2.1; 2.4], 1.7 [CI% 1.5; 1.9] and 1.2 [CI% 0.9; 1.5] mm Hg/ml, respectively (p1-2-3 <0.01). The Ea/BSA index in the 1st group was 0.92 [CI% 0.85; 1.0], in the 2nd group – 1.0 [CI% 0.94; 1.13], in the third group – 1.16 [CI% 0.99; 1.33] mm Hg/ml/m2 (p1–3 = 0.01). The Ees/BSA indicator in the comparison groups was 1.16 [CI% 1.08; 1.24], 0.88 [CI% 0.79; 0.98] and 0.64 [CI% 0.46; 0.82] mm Hg/ml/m2, respectively (p1-2-3 <0.01). The Ea/Ees index was the smallest in the 1st group – 0.8 [CI% 0.8; 0.9]; higher in the 2nd group – 1.2 [CI% 1.1; 1.3]; the maximum values were registered in the 3rd group – 1.9 [CI% 1.7; 2.0] (p1-2-3 <0.0001). Conclusions In STEMI patients with mid-range and reduced EF, high values of the LVAC index were revealed, which is due to a decrease in left ventricular elastance due to impaired LV contractility. Funding Acknowledgement Type of funding sources: None.

Comprehensive Physiological Modeling Provides Novel Insights Into Heart Failure With Preserved Ejection Fraction Physiology.

BackgroundAlthough a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls.Methods and ResultsWe performed simultaneous right‐heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient‐level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V30, the end‐diastolic pressure–volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, P<0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, P<0.001). During exercise, the magnitude of the change in stressed blood volume (r=0.67, P<0.001) and left ventricular stiffness (r=−0.44, P<0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non‐linear interaction between circulatory parameters.ConclusionsThe circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.

Sex differences in cardiovascular adaptations in recreational marathon runners.

There are well-established sex differences in central hemodynamic and cardiac adaptations to endurance exercise; however, controversial evidence suggests that excessive endurance exercise may be related to detrimental cardiovascular adaptations in marathoners. To examine left ventricle (LV) structure, LV function, 24-h central hemodynamics and ventricular-vascular coupling in male and female marathoners and recreationally active adults. 52 marathoners (41 ± 5years, n = 28 female, completed 6 ± 1marathons/3years) and 49 recreationally active controls (42 ± 5years, n = 25 female) participated in the study. Three-Dimensional Echocardiography (3DE) was used to measure LV mass index and LV longitudinal (LS) circumferential (CS), area (AS), and radial strain (RS). An ambulatory blood pressure (BP) cuff was used to measure 24-h central hemodynamics (BP, pulse wave velocity, PWV, wave reflection index, RIx). Hemodynamic and 3DE measures were combined to derive the ratio of arterial elastance (Ea) to ventricular elastance (Elv) as a global measure of ventricular-vascular coupling. There were no sex or group differences in LS, CS, AS, and RS (p > 0.05). Females marathoners had similar aortic BP (116 ± 9 vs. 113 ± 1mmHg), and PWV (5.9 ± 0.5 vs. 5.9 ± 1.1m/s) compared to female controls but lower aSBP (116 ± 9 vs. 131 ± 10mmHg) and PWV (5.9 ± 0.5 vs. 6.2 ± 0.5m/s) compared to male marathoners (p < 0.05). Female marathoners had lower Ea/Elv than female controls (0.67 ± 0.20 vs. 0.93 ± 0.36) and male marathoners (0.67 ± 0.20 vs. 0.85 ± 0.42, p < 0.05). Women that have completed multiple marathons do not have reduced LV function or increased aortic stiffness and may have better ventricular-vascular coupling compared to male marathoners and their female untrained counterparts.

CMR derived ventricular arterial coupling in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Ventriculoarterial coupling (VAC) is an important surrogate measurement of global cardiovascular efficiency. However, up till recently, this measurement has been rarely used in clinical practice. This could be due to its invasive nature, and the relatively complex methods required for acquisition and interpretation. We here describe a noninvasive method of measuring VA coupling using cardiac magnetic resonance (CMR) in a cohort of hypertrophic cardiomyopathy (HCM). Methods Cardiac MRI was performed in 61 patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after undergoing extended surgical myectomy. Cardiac MRIs from 15 patients with non-obstructive HCM were also included for comparison. Hypertensive patients were excluded from this study. Vitals signs were recorded during each MRI study. Arterial end-systolic pressure (AESP) was determined non-invasively as previously described (0.9x brachial blood pressure). Left ventricular end-systolic pressure (LVESP) was calculated by adding the echo-derived peak systolic gradient across the left ventricular outflow tract to the arterial end-systolic pressure. Indexed stroke volume (SVI) in the ascending aorta as well as indexed end systolic volume (ESVI) were calculated from CMR. Indexed arterial (Ea) and ventricular (Ev) elastance were calculated as AESP/SVI and LVESP/ESVI. VA coupling was then calculated as Ea/Ev. Results Compared to the baseline measurements, VAC increased significantly post myectomy (mean VAC pre-myectomy and post-myectomy 0.38 vs. versus 0.62 respectively, p= 0.00001). VAC in non-obstructive HCM patients (mean = 0.64) was statistically similar to that in post-myectomy (p = 0.82) and statistically different from pre-myectomy (p = 0.00016). The mean of LVOTO gradients post- and pre-myectomy were significantly different (p = 0.00001). Significant correlation of the delta-VAC with the delta gradient in the LVOTO was found (r= 0.35, p = 0.005). Conclusion Non-invasive assessment of VA coupling using CMR is feasible and could be a useful tool in the evaluation of patients with various cardiovascular disorders. Further studies with larger numbers of patients are required to establish the utility of this method in clinical practice.

Non-invasive quantification of pressure-volume loops from cardiovascular magnetic resonance at rest and during dobutamine stress.

Non-invasive quantification of pressure-volume (PV) loops from brachial pressure and cardiovascular magnetic resonance is a validated method but its application has been limited to resting heart rates. The aim of this study was to improve the previous method and validate it against invasive left-ventricular pressure measurements in an experimental porcine model, and further apply it to 16healthy humans at rest and during dobutamine stress. In addition, the improved method calculates the arterial elastance which provides the computation of the ratio of effective arterial (Ea ) to maximal ventricular elastance (Emax ) representing the ventricular-arterial coupling. In the porcine model, the differences between the improved non-invasively derived PV loops and invasively measured PV loops were for stroke work (mean±SD) 0.00±0.03J, ventricular efficiency -1.1±0.4%, and contractility 1.1±0.1mmHg/ml. In human subjects during dobutamine stress, stroke work increased from 1.3±0.3 to 1.7±0.4J, ventricular efficiency from 71±4 to 82±4%, contractility from 1.3±0.2 to 2.3±0.6mmHg/ml, and the ratio of arterial to ventricular elastance decreased from 0.96 to 0.56. The improved method for non-invasive PV loops constitutes a more robust diagnostic tool for cardiac disease states in a wider range of study cohorts at both rest and during stress.

Sensitivity Analysis of Single Beat Left Ventricular Elastance Estimation by Chen Method.

Left ventricular (LV) end-systolic elastance (Ees) can be estimated using single-beat (Ees(sb)) Chen method, employing systolic and diastolic arm-cuff pressures, stroke volume (SV), ejection fraction and estimated normalized ventricular elastance at arterial end-diastole. This work aims to conduct a sensitivity analysis of Chen formula to verify its reliability and applicability in clinical scenario. Starting from a baseline condition, we evaluated the sensitivity of Ees(sb) to the parameters contained in the formula. Moreover, a mathematical model of the cardiovascular system was used to evaluate the sensitivity of Ees(sb) to end-diastolic LV elastance (Eed), Ees, arterial systemic resistance (Ras) and heart rate (HR). In accordance with Ees definition, Ees(sb) increases by increasing aortic pressure and pre-ejection time, reaching the highest value for a pre-ejection time = 40 ms, and then decreases. In contrast with Ees definition, Ees(sb) increases (from 3.21 mmHg/mL to 12.15 mmHg/mL) by increasing the LV end-systolic volume and decreases by increasing the SV. In the majority of the analysis with the mathematical model, Ees was underestimated using the Chen method: by increasing Ees (from 0.5 to 2.5 mmHg/mL), Ees(sb) passes only from 0.56 to 1.54 mmHg/mL. Ees(sb) increases for higher Eed (from 1.03 to 2.33 mmHg/mL). Finally, Ees(sb) decreases (increases) for HR < 50 bpm (< 50 bpm), and for Ras < 1100 mmHg/gcm4 (> 1100 mmHg/gcm4). Unexpectedly Ees(sb) increases for higher LV end-systolic volume and decreases for higher SV. These results contrast with Ees definition, which is the ratio between the LV end-systolic pressure and the LV end-systolic volume. Moreover, Ees(sb) is influenced by cardiocirculatory parameters such as LV Eed, HR, Ras, ejection time, and pre-ejection time. Finally, Ees(sb) computed with the model output often underestimates model Ees.

Early Identification of Patients at Risk for Incident Heart Failure With Preserved Ejection Fraction: Novel Approach to Echocardiographic Trends

BackgroundHeart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence with a 50% mortality rate within 3 years of diagnosis, but lacking effective evidence-based therapies. Specific echocardiographic markers are not typically used to trigger alarm before acute HFpEF decompensation. The goal of this study was to retrospectively track changes in echocardiographic markers leading to the time of incident HFpEF hospitalization. Methods and ResultsIn a single-center, retrospective analysis, patients with HFpEF admitted between 2007 and 2014 were identified using the International Classification of Diseases, 9th Revision with search refined using the European Society of Cardiology HFpEF guidelines. Using linear mixed effects models, changes in echocardiographic markers preceding acute HF decompensation owing to incident HFpEF were analyzed. We report on an incident HFpEF cohort of 242 patients, extending 18 years retrospectively, and including 675 echocardiograms analyzed from the overall sample at 14 distinct time intervals before acute decompensation. The regression models demonstrated 3 echocardiographic markers with statistically significant increases across multiple time intervals including, arterial elastance (P = .006), right atrial pressure estimate (P < .001), and right ventricular systolic pressure (P = .006). Other echocardiographic markers had individual time intervals with significant increases before acute decompensation, including (a) left atrial diameter, 8 to 10 years before HFpEF diagnosis, (b) left ventricular filling pressure 2 to 6 years before HFpEF diagnosis, (c) ventricular elastance 3 to 6 months before HFpEF diagnosis, and (d) ventricular elastance/arterial elastance as early as 10 to 20 years and as late as 3 to 6 months before HFpEF diagnosis. Furthermore, African Americans presented with incident HFpEF at an average younger age than White patients (65.6 ± 15.2 years vs. 76.7 years ± 11.7, P < .001). ConclusionsNoninvasive echocardiographic markers associated with incident HFpEF diagnosis showed long, mid, and acute range, significant changes as far back as 10 to 20 years and as close as 3 to 6 months before acute HFpEF decompensation. Including a diverse study cohort is critical to understanding the phenotypic differences of HFpEF. This hypothesis-generating study identified a novel approach to identifying trends in echocardiographic markers that may be used as a signal of impending incident HFpEF.

Dynamic Arterial Elastance Is Associated With the Vascular Waterfall in Patients Treated With Norepinephrine: An Observational Study.

Introduction: It has been suggested that dynamic arterial elastance (Eadyn) can predict decreases in arterial pressure in response to changing norepinephrine levels. The objective of this study was to determine whether Eadyn is correlated with determinants of the vascular waterfall [critical closing pressure (CCP) and systemic arterial resistance (SARi)] in patients treated with norepinephrine.Materials and Methods: Patients treated with norepinephrine for vasoplegia following cardiac surgery were studied. Vascular and flow parameters were recorded immediately before the norepinephrine infusion and then again once hemodynamic parameters had been stable for 15 min. The primary outcomes were Eadyn and its associations with CCP and SARi. The secondary outcomes were the associations between Eadyn and vascular/flow parameters.Results: At baseline, all patients were hypotensive with Eadyn of 0.93 [0.47;1.27]. Norepinephrine increased the arterial blood pressure, cardiac index, CCP, total peripheral resistance (TPRi), arterial elastance, and ventricular elastance and decreased Eadyn [0.40 (0.30;0.60)] and SARi. Eadyn was significantly associated with arterial compliance (CA), CCP, and TPRi (p < 0.05).Conclusion: In patients with vasoplegic syndrome, Eadyn was correlated with determinants of the vascular waterfall. Eadyn is an easy-to-read functional index of arterial load that can be used to assess the patient’s macro/microcirculatory status.Clinical Trial Registration: ClinicalTrials.gov #NCT03478709.

Baroreceptor Unloading at Rest and During Exercise in Heart Failure Exacerbates Ventricular‐Vascular Coupling

The arterial baroreflex is the primary reflex controlling arterial blood pressure on a beat-by-beat basis via modulation of autonomic output to change cardiac output and systemic vascular resistance. This moment-to-moment control of arterial pressure is well maintained with the transition from rest to exercise. However, in systolic heart failure (HF) baroreflex dysfunction can occur. Effective control of cardiac output occurs in part via efficient energy transfer from the left ventricle to the systemic circulation; known as ventricular-vascular coupling. Ventricular-vascular coupling can be evaluated by changes in stroke work and the relationship between effective arterial elastance to left ventricular maximal elastance. We investigated if the effects of baroreceptor unloading (via bilateral carotid occlusion) on effective arterial elastance and stroke work at rest, and during exercise were altered in HF, in conscious chronically instrumented canines. We hypothesized that in healthy subjects the baroreflex maintains ventricular-vascular coupling whereas in HF, exacerbated increases in effective arterial elastance as a result of baroreceptor unloading would cause decoupling of the ventricular-vascular interaction. We observed in healthy subjects that baroreceptor unloading significantly increased effective arterial elastance (Ea) and stroke work (SW) at rest (Ea: +1.6 ± 0.2 mmHg/ml) (SW: +1.8 ± 0.1 L/mmHg) and during exercise (Ea: +1.4 ± 0.2 mmHg/ml) (SW: +1.6 ± 0.2 L/mmHg) thus maintaining ventricular-vascular coupling. In HF, ventricular-vascular uncoupling is already apparent with higher effective arterial elastance and reduced maximal ventricular elastance. Baroreceptor unloading in HF further worsens ventricular-vascular coupling at rest and during exercise by eliciting ~2-3 fold increases in effective arterial elastance (EaΔREST +4.3 ± 0.3 mmHg/ml) (EaΔEX +2.5 ± 0.5 mmHg/ml) unaccompanied by much improvement in stroke work (SWΔREST +0.1 ± 0.5 L/mmHg) (SWΔEX +0.5 ± 0.1 L/mmHg). We conclude that the ability of the arterial baroreflex to raise cardiac output in heart failure is impaired in part due to further reflex induced uncoupling of the ventricular-vascular relationship. This likely contributes to impaired reflex control of arterial pressure during hypotensive challenges in HF.

AI-Based Estimation of End-Systolic Elastance From Arm-Pressure and Systolic Time Intervals.

Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular-arterial interaction. Previous methods for the Ees estimation require the use of the echocardiographic ejection fraction (EF). However, given that EF expresses the stroke volume as a fraction of end-diastolic volume (EDV), accurate interpretation of EF is attainable only with the additional measurement of EDV. Hence, there is still need for a simple, reliable, noninvasive method to estimate Ees. This study proposes a novel artificial intelligence—based approach to estimate Ees using the information embedded in clinically relevant systolic time intervals, namely the pre-ejection period (PEP) and ejection time (ET). We developed a training/testing scheme using virtual subjects (n = 4,645) from a previously validated in-silico model. Extreme Gradient Boosting regressor was employed to model Ees using as inputs arm cuff pressure, PEP, and ET. Results showed that Ees can be predicted with high accuracy achieving a normalized RMSE equal to 9.15% (r = 0.92) for a wide range of Ees values from 1.2 to 4.5 mmHg/ml. The proposed model was found to be less sensitive to measurement errors (±10–30% of the actual value) in blood pressure, presenting low test errors for the different levels of noise (RMSE did not exceed 0.32 mmHg/ml). In contrast, a high sensitivity was reported for measurements errors in the systolic timing features. It was demonstrated that Ees can be reliably estimated from the traditional arm-pressure and echocardiographic PEP and ET. This approach constitutes a step towards the development of an easy and clinically applicable method for assessing left ventricular systolic function.

An approach to early stage detection of atherosclerosis using arterial blood pressure measurements

Atherosclerosis is a pathological condition that develops gradually over the years and may eventually lead to a heart attack, a stroke, or a peripheral vascular disease, depending upon its site of occurrence in the human arterial network. We aim to detect this pathological condition in its early stage so that the necessary measures can be taken timely. To achieve this, a third-order nonlinear model of the cardiovascular system is considered, having states as systemic arterial and venous pressures along with the left ventricular volume. The available measurement signal is arterial blood pressure taken from the radial artery. This paper proposes the idea of online tracking of model parameters by utilizing an unscented Kalman filter (UKF) based framework that would help monitor the above-mentioned pathological condition. Furthermore, a classification approach has been presented, which carries out screening of subjects suffering from atherosclerotic cardiovascular diseases (CVDs) while utilizing estimates obtained from the UKF framework. It is observed that clinical quantities such as arterial compliance, systolic blood pressure, and ventricular elastance play an important role in the development of atherosclerosis. The classification results are quite encouraging. The proposed framework regularly monitors the atherosclerotic condition and has a potential for the early-stage screening of subjects suffering from atherosclerosis. With an increase in sedentary lifestyle in modern world, an early-stage screening of atherosclerotic cardiovascular diseases would be an important contribution to the healthcare and biomedical community.

Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis

Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not.

DISTURBED LEFT ATRIAL CONDUIT FUNCTION IN HYPERTENSIVE PATIENTS

Abstract Objective: Arterial stiffness is an independent risk factor in arterial hypertension, but little is known about the association between left atrial remodeling and arterial stiffness in middle – aged hypertensive patients. AIM: To investigate the early changes in left atrial (LA) mechanical function and parameters of arterial stiffness in a population of asymptomatic hypertensive individuals. Design and method: A total 95 patients (57 ± 14 years) with hypertension, were separated in two groups: 22 patients with normal EA/Ees ratio (Arterial elastance (AE) and ventricular elastance (Ees))and 73 hypertensive patients with decrease EA/Ees ratio, marker for ventriculo – arterial coupling (VAC). All patients underwent standard two - dimentional echocardiography with Speckle tracking analysis for LA – reservoir (LARs), conduit (LAScd) and contractile (LASct) strain. End – systolic pressure was determined from the brachial pulse wave. Arterial elastance (AE) and ventricular elastance (Ees) were calculated as and – systolic pressure/stroke volume and end – systolic pressure/end – systolic volume. Parameters for arterial stiffness – 24 - hour central systolic pressure (cSys24 h) and central pulse pressure (cPP24 h) were measured non – invasively with oscillometric method by Mobil-O-graph PWA. Results: RESULTS: Statistically significant differences in parameters of vascular stiffness were found in patients with normal VAC in comparison with disturbed EA/Ees: cSys24 h (107.64 ± 9.19 vs. 116.64 ± 16.7 mm Hg, p = 0.02), cPP24 h (40.23 ± 11.84 vs. 48.08 ± 10.51 mm Hg, p = 0.04). There were statistically significant differences in echocardiography parameters between patients with disturbed VAC in comparison to other group: LAScd (16.86 ± 1.94 vs. 19.49 ± 1.35 %, p &lt; 0.001), LASr (30.22 ± 3.26 vs. 31.81 ± 5.32 %, p = 0.007) and LAVI (30.95 ± 9.22 vs. 36.65 ± 8.83 ml/m2, p = 0.007). There was positive correlation between LAScd with EA/Ees (r = 0.272, p &lt; 0.008) and negative E/Em (r = -0.264, p &lt; 0.01). LAVI correlated moderate positively with E/Em ratio (r = 0.407, p &lt; 0.0001) and negatively with LAScd (r = - 0.410, p &lt; 0.0001). Conclusions: LA mechanical deformation is dependent to arterial stiffness. Reduced LAScd could play a key role in early stages of atrial remodeling. These findings could be used for the prediction of cardiovascular events in this population.

INTERRELATION OF INDICATORS OF LEFT VENTRICULAR-ARTERIAL COUPLING AND PARAMETERS OF LOCAL ARTERIAL STIFFNESS IN THE POSTINFARCTION PERIOD

Objective: To study the correlations between the parameters of the left ventricular-arterial coupling (LVAC) and the parameters of local arterial stiffness in patients after STEMI 6 months after revascularization. Design and method: 125 patients (mean age 51.2 ± 8.8 years) after STEMI were included in the study. The diagnosis was confirmed by biomarkers of myocardial necrosis, ECG, coronary angiography. Echocardiography was performed at the 7–9th day and 6 months after STEMI (MyLab, Esaote, Italy), followed by calculation of LVAC indices: arterial elastance (Ea), left ventricular elastance (Ees), LVAC index (Ea/Ees). The study of the right and left common carotid arteries (CCA) was carried out on a MyLab ultrasound scanner (Esaote, Italy) using high-frequency RF signal technology. The following parameters were recorded: QIMT - intima-media thickness, DC - lateral distensibility coefficient, stiffness index β, loc Psys - local SBP, locPdia - local DBP, locPWV - local pulse wave velocity, AP - amplification pressure. Results: In the study of the correlation of LVAC indices with the CCA rigidity parameters recorded on 7–9th day from the STEMI, a relationship was revealed only between Ees and LocPsys (r = 0.40; p = 0.01), Ees and LocPdia (r = 0, 26; p = 0.004). After 6 months of follow-up, a closer relationship between the LVAC and the parameters of the local CCA stiffness was diagnosed. The Ea indicator correlated with DC (r = -0.23; p = 0.009), PWV (r = 0.21; p = 0.02), LocPsys (r = 0.33; p = 0.0002), LocPdia (r = 0.26; p = 0.004) and AP (r = 0.19; p = 0.03). The Ees indicator was found to be associated with LocPsys (r = 0.38; p = 0.00001), LocPdia (r = 0.27; p = 0.002), AP (r = 0.22; p = 0.01). Conclusions: After 6 months, there was a closer correlation between the LVAC indices and the parameters of local pressure and rigidity. This is probably partly due to the remodeling of the cardiovascular system in the postinfarction period and the inclusion of compensatory-adaptive mechanisms that ensure the contractile function of the heart.

DYNAMICS OF INDICES OF LEFT VENTRICULAR-ARTERIAL COUPLING IN PATIENTS WITH HYPERTENSION AFTER ACUTE MYOCARDIAL INFARCTION

Objective: To study the dynamics of left ventricular-arterial coupling (LVAC) indices in patients with arterial hypertension (AH) after STEMI, depending on the presence or absence of rapidly progressing left ventricular (LV) remodeling. Design and method: The study included 71 patients (mean age 51.4 ± 8.4 years) with hypertension after STEMI. Echocardiography was performed at the 7–9th day and 24th, 48th weeks after STEMI (MyLab, Esaote, Italy) with the determination of EDV, its index (EDVi) and calculation of LVAC indices: arterial elastance (Ea), LV elastance (Ees), LVAC index (Ea/Ees). All patients received STEMI treatment for 48 weeks. Results: According to the EDVi dynamic during the 24 weeks, the patients were divided into two groups: group 1 - 30 people with rapidly progressive LV remodeling (increase in the EDVi &gt; 20%); group 2 - 41 people without LV remodeling (EDVi dynamics &lt; 20%). The following dynamics of LVAC indices was revealed: in group 1 Ea initialy was 2.0[95%CI 1.8;2.2], after 24 weeks - 1.6 [95%CI 1.4;1.8] (p = 0.0003), 48 weeks - 1.8[95%CI 1.5;2.0] (p = 0.0007); in group 2, respectively, 1.9[95%CI 1.7;2.1], 1.9[95%CI 1.7;2.0] (p = 0.46), 1.8[95%CI 1.7;1.9] (p = 0.27). Ees in the 1st group initially 1.8[95%CI 1.4;2.3], after 24 weeks - 1.2[95%CI 0.9;1.6] (p = 0.0002), 48 weeks - 1.3[95%CI 1.1;1.6] (p = 0.0001); in group 2 - 2.0[95%CI 1.9;2.2], 2.2[95%CI 2.0;2.4] (p = 0.08), 2.3[95%CI 2.1;2.5] (p = 0.009). In the 1st group the Ea/Ees index initially corresponded to normal values: 1.2[95 CI 1.0;1.4], followed by an increase after 24 weeks to 1.4 [95% CI 1.1; 1.6] (p = 0.007) and after 48 weeks - 1.4[95%CI 1.2;1.7] (p = 0.002). In the 2nd group, a decrease of Ea/Ees was revealed: initially - 1.0[95%CI 0.9;1.1], after 24 weeks - 0.9[95%CI 0.8;0.9] (p = 0.02), 48 weeks - 0.8[95%CI 0.7;0.9] (p = 0.002). Conclusions: In the group of patients, against the background of the development of rapidly progressive LV remodeling after STEMI in combination with hypertension, a pathological increase in the LVAC index was revealed due to a more pronounced decrease in left ventricular elastance, which reflects impaired homeostasis of the cardiovascular system.

Biventricular function in exercise during autonomic (thoracic epidural) block

BackgroundBlockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand.MethodsIn a cross-over design, 12 patients scheduled to undergo thoracic surgery performed dynamic ergometric exercise tests with and without TEA. Hemodynamics were monitored and biventricular function was measured by transthoracic two-dimensional and M-mode echocardiography, pulsed wave Doppler and tissue Doppler imaging.ResultsTEA attenuated systolic RV function (TV Sʹ: − 21%, P < 0.001) and LV function (MV Sʹ: − 14%, P = 0.025), but biventricular diastolic function was not affected. HR (− 11%, P < 0.001), SVI (− 15%, P = 0.006), CI (− 21%, P < 0.001) and MAP (− 12%, P < 0.001) were decreased during TEA, but SVR was not affected. Exercise resulted in significant augmentation of systolic and diastolic biventricular function. During exercise HR, SVI, CI and MAP increased (respectively, + 86%, + 19%, + 124% and + 17%, all P < 0.001), whereas SVR decreased (− 49%, P < 0.001). No significant interactions between exercise and TEA were found, except for RPP (P = 0.024) and MV E DT (P = 0.035).ConclusionCardiac sympathetic blockade by TEA reduced LV and RV systolic function but did not significantly blunt exercise-induced increases in LV and RV function. These data indicate that additional mechanisms besides those controlled by the cardiac sympathetic nervous system are involved in the regulation of cardiac function during dynamic exercise.Trial registration Clinical trial registration: Nederlands Trial Register, NTR 4880 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4880.