Ventricular End-systolic Elastance Research Articles

Association of prior tuberculosis with cardiovascular status in perinatally HIV-1-infected adolescents

BackgroundWhether, and how, co-occurring HIV-1 infection (HIV) and tuberculosis (TB) impact cardiovascular status, especially in adolescents with perinatally acquired HIV (APHIV), have not been examined. We hypothesised that APHIV with...

Ventriculo-arterial coupling parameters by cardiac magnetic imaging are associated with outcome in patients with a systemic right ventricle

Abstract Introduction Invasive studies have shown that patients with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (TGA) or complete TGA after atrial switch procedure possess impaired ventriculo-arterial coupling (VAC) parameters. The randomized, placebo-controlled, double-blinded, multi-centre SERVE trial investigated the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients on RV endsystolic volume (RVESV), with negative results. Aim of this sub-analysis was to evaluate changes of non-invasively assessed VAC parameters over time and for treatment effect. We prospectively analysed whether VAC parameters predict clinical outcome in sRV patients. Methods Volumetric RV parameters and aortic flow were assessed by cardiac magnetic resonance (CMR) and analysed (blinded for patient and assessment time and treatment) at baseline, after 3 years, or after 1 year if the study drug was withdrawed. Parameters were compared with clinical outcome at each visit. Effective arterial elastance Ea was calculated as RV endsystolic pressure (RVesp) / aortic forward flow, with RVesp defined as 0.9 x systolic blood pressure. Right ventricular endsystolic elastance Ees was calculated by RVesp / RVESV, and RV VA-coupling ratio was expressed as Ea/Ees. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of > 4th quartile were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure. Results CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at follow-up (FU). No effect of tadalafil compared to placebo was evident for effective arterial elastance Ea (p=0.35), ventricular endsystolic elastance Ees (p=0.11), VAC Ea/Ees (p=0.82), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over the 3 years FU-time, Ea (p=0.24) and RVEF (p=0.11) did not change, whereas Ees mildly decreased (p=0.0052, fig. 1 A) and Ea/Ees increased (p=0.013, fig. 1 B). During FU, 14 patients experienced a clinical event. An Ees <0.73 mmHg/ml and an Ea/Ees ratio of >1.94 were associated with adverse clinical outcomes (for both p=0.004, fig. 2). Conclusion In sRV patients, treatment with tadalafil had no effect on VAC parameters compared to placebo. CMR-derived ventricular endsystolic elastance (Ees) and Ea/Ees ratio changed over the FU of 3 years and were associated with adverse clinical outcome.Figure 1Figure 2

Left ventricular end-systolic and diastolic elastance as predictors of cardiac events in patients who underwent mitral valve surgery for severe mitral regurgitation

Abstract Background/Introduction In severe mitral regurgitation (MR), the prognostic significance of left ventricular ejection fraction (LVEF) and LV dimensions is well-established. However, the assessment of diastolic function in this patient presents a notable challenge, and its impact on postoperative outcomes remains unclear. Purpose This study was designed to explore the potential of LV end-systolic (Ees) and diastolic elastance (Eed) as novel predictors for cardiac events following surgery. Methods A retrospective cohort study was performed on 199 patients (53% male, average age 60 years, mean LVEF 60.0%) with severe MR and undergoing surgery. Preoperative Ees and Eed were calculated using established formulas: Ees = (systolic blood pressure x 0.9) / LV end-systolic volume, and Eed = left atrial pressure / stroke volume, with left atrial pressure estimated from mitral Doppler flow parameters as SBP – (4 x peak MR velocity²). The primary outcome was defined as either cardiac death or hospitalization due to heart failure. Results Average values for Ees and Eed were 2.61 (IQR: 1.67-3.20) and 0.32 (IQR: 0.05-0.57), respectively. Univariate analysis indicated Ees (HR: 1.24, 95% CI: 0.99-1.57, p = 0.066) and Eed (HR: 5.93, 95% CI: 2.87-12.26) as potential predictors. Adjusting for age, LVEF, and LV dimensions, Eed remained an independent predictor of cardiac events (HR: 5.89, 95% CI: 2.81-12.28). Stratifying Eed at a threshold of 0.31—identified as best sum of sensitivity and specificity—revealed that Eed > 0.31 were associated with a 3.9-fold increase in cardiac events compared to those with Eed ≤ 0.31 (p = 0.008). (Fig.) Conclusions The assessment of Eed is a straightforward and readily available parameter in routine clinical practice. Our findings advocate for the inclusion of preoperative Eed evaluation as an independent prognostic indicator for patients undergoing surgery for severe MR.Event free survival by Eed

Physiological control for left ventricular assist devices based on deep reinforcement learning.

The improvement of controllers of left ventricular assist device (LVAD) technology supporting heart failure (HF) patients has enormous impact, given the high prevalence and mortality of HF in the population. The use of reinforcement learning for control applications in LVAD remains minimally explored. This work introduces a preload-based deep reinforcement learning control for LVAD based on the proximal policy optimization algorithm. The deep reinforcement learning control is built upon data derived from a deterministic high-fidelity cardiorespiratory simulator exposed to variations of total blood volume, heart rate, systemic vascular resistance, pulmonary vascular resistance, right ventricular end-systolic elastance, and left ventricular end-systolic elastance, to replicate realistic inter- and intra-patient variability of patients with a severe HF supported by LVAD. The deep reinforcement learning control obtained in this work is trained to avoid ventricular suction and allow aortic valve opening by using left ventricular pressure signals: end-diastolic pressure, maximum pressure in the left ventricle (LV), and maximum pressure in the aorta. The results show controller obtained in this work, compared to the constant speed LVAD alternative, assures a more stable end-diastolic volume (EDV), with a standard deviation of 5 mL and 9 mL, respectively, and a higher degree of aortic flow, with an average flow of 1.1 L/min and 0.9 L/min, respectively. This work implements a deep reinforcement learning controller in a high-fidelity cardiorespiratory simulator, resulting in increases of flow through the aortic valve and increases of EDV stability, when compared to a constant speed LVAD strategy.

U-shaped prognostic value of left ventricular-arterial coupling in septic patients: a prospective study

BackgroundVentricular-arterial coupling (VAC) has garnered increasing interest in critical care. The prognostic significance of left ventricular-arterial coupling (LVAC) in this context remains a topic of debate.ObjectiveThis study aimed to explore the association between LVAC and patient outcomes in sepsis.MethodsPatients with sepsis or septic shock admitted to the intensive care unit (ICU) were included. LVAC was evaluated using the arterial elastance (Ea)/left ventricular end-systolic elastance (Ees) ratio. Prognostic indicators, including 30-day mortality, length of ICU stay, mechanical ventilation (MV), changes in delta lactate levels, and oxygen index were also collected.ResultsA total of 388 patients were enrolled in this study. A U-shaped relationship was observed between LVAC and 30-day mortality, with an optimal LVAC value of 1.19 identified. For LVAC values above 1.19, the odds ratio (OR) for 30-day mortality was 1.07 (95% confidence interval [CI] 1.01–1.14). Below this threshold, OR was 0.85 (95% CI 0.73, 0.99). Similarly, in the curve for ICU-free days, a β value of − 8.64 (95% CI − 16.53, − 0.76) was noted for LVAC values over 1.26. For ventilator-free time, the kink point was 1.24, with significant β values on both sides of this threshold [− 226.49 (95% CI − 411.59, − 41.38) and 147.67 (95% CI 12.40, 282.93), respectively].ConclusionsThis study established U-shaped associations between LVAC and various clinical outcomes in septic patients. Optimizing LVAC could potentially enhance patient prognosis. Given the slight variations in optimal LVAC values across different patient populations, individualized LVAC titration may be beneficial in improving clinical outcomes.

Association of ventricular-arterial coupling with biomarkers involved in heart failure pathophysiology-the STANISLAS cohort.

Impaired left ventricular-arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population-based cohort of middle-aged individuals. In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF-related proteins with non-invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (Ea)/ventricular end-systolic elastance (Ees). Among the 32 tested proteins, fatty acid-binding protein adipocyte 4, interleukin-6, growth differentiation factor 15, matrix metalloproteinase (MMP)-1, and MMP-9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP-2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were negatively associated. In multivariable models, only MMP-2 and NT-proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT-proBNP were also negatively associated with Ea/Ees in the whole cohort but this association did not persist in the parent subgroup. Elevated MMP-2 and NT-proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload.

Analysis of ventricular-vascular properties during preeclampsia: an echocardiography study.

The aim of the study is to analyze ventricular-vascular properties with different ventricular-arterial coupling (VAC) ratio in the preeclamptic women. Seventy-seven pregnant women with preeclampsia and eighty-nine with normal pregnancy were performed echocardiography. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees). Using the VAC value of 0.8 as the cut-off near uncoupling, the preeclampsia cases were divided into two subgroups: VAC ratio ≥ 0.8 and <0.8. Cardiac structure and function, VAC properties, as well as four components of the LV pressure-strain loop, including global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were determined. The preeclampsia with VAC ≥ 0.8 had an enlarger indexed ventricular volume and a thicker relative ventricular wall than the VAC < 0.8. The Ees significantly increased in the subgroup with VAC < 0.8 and decreased in the VAC ≥ 0.8, while the Ea increased in both of them. The preeclampsia with VAC ≥ 0.8 showed an obvious augmentation in GWI, GCW and GWE, along with a similar GWW compared to those with VAC < 0.8. There were variable relationships between the LV pressure-strain components and VAC properties. Thus, the preeclampsia with VAC ≥ 0.8 undergoes a more adverse remodeling and a greater impact on cardiac contractility. The increased stiffness of the heart and arterial system, and increased resistance of peripheral vessels net lead to the deteriorative ventricular efficiency with elevated myocardial oxygen consumption during a preeclampsia pregnancy.

Echocardiographic Predictors of Readiness for Double Switch Operation and Postoperative Ejection Fraction in Patients With Congenitally Corrected Transposition of the Great Arteries Undergoing Left Ventricular Retraining

In patients with congenitally corrected transposition of the great arteries (ccTGA), assessment of readiness for the double switch operation (DSO) after pulmonary arterial band (PAB) placement involves cardiac magnetic resonance imaging (cMRI) to measure left ventricular ejection fraction (LVEF) and mass and cardiac catheterization (catheterization) to assess the ratio of left ventricular to right ventricular pressure (LV:RVp). The aims of this study were to describe the relationships between echocardiographic and catheterization and cMRI measures of readiness for DSO and to develop risk factors for left ventricular (LV) dysfunction after DSO on the basis of echocardiographic measures of ventricular-arterial coupling (VAC). Patients with ccTGA undergoing LV retraining at a DSO referral center were reviewed. LVEF measured by echocardiography was compared with that measured by cMRI, and LV:RVp measured by echocardiography was compared with that measured by catheterization using Bland-Altman analysis. The relationship between preoperative VAC markers and postoperative echocardiography was analyzed using ventricular end-systolic elastance (EES) and a novel marker consisting of the product of LVEF and LV:RVp (EFPR). Thirty-one patients with 56 evaluations for DSO were included, 24 of whom underwent DSO. Echocardiographic LVEF correlated well with cMRI LVEF (r=0.79), and Bland-Altman analysis slightly overestimated cMRI LVEF (mean difference,+3%). Echocardiographic LVEF had a moderate ability to identify normal cMRI LVEF (area under the curve, 0.80) and at an optimal cut point of echocardiographic LVEF threshold of 61%, there was 71% sensitivity and 76% specificity to detect cMRI LVEF≥55%. Echocardiographic LV:RVp correlated well with LV/RVp by catheterization (r=0.77) and slightly underestimated the catheterization value (mean difference, -0.11). Echocardiographic LV:RVp had a good ability to identify adequate LV:RVp by catheterization (area under the curve, 0.95) and at an optimal echocardiography cut point of 0.75 had 100% sensitivity and 85% specificity to detect a catheterization LV:RVp >0.9. Echocardiography-based criteria for DSO readiness (echocardiographic LVEF of 61% and LV:RVp of 0.75) demonstrated specificity of 97% and positive predictive value of 96% for published criteria of DSO readiness (cMRI LVEF of 55% and catheterization LV:RVp of 0.9). EES and EFPR correlated with post-DSO LVEF (ρ=0.72 and ρ=0.60, respectively). EFPR of 0.51 demonstrated 78% sensitivity and 100% specificity for post-DSO LV dysfunction (LVEF<55%). Age at first PAB also strongly correlated with post-DSO LVEF (ρ=0.75). No patient with first PAB at <1year of age exhibited post-DSO LV dysfunction. Echocardiographic measures of LVEF and LV:RVp are reliable indicators of reference standard modalities and can guide management during retraining. The preoperative VAC markers EES and EFPR may be useful markers of post-DSO LV dysfunction. Values of echocardiographic LV:RVp >0.75 are likely to meet pressure-generation criteria for DSO and should be considered for referral to catheterization and cMRI evaluation for DSO. PAB placement before 1year of life may optimize LV outcomes in patients considered for DSO.

Reducing Left Ventricular Wall Stress through Aortic Valve Enlargement via Transcatheter Aortic Valve Implantation in Severe Aortic Stenosis.

Background: In aortic stenosis, the left ventricle exerts additional force to pump blood through the narrowed aortic valve into the downstream arterial vasculature. Adaptive hypertrophy helps to maintain wall stress homeostasis but at the expense of impaired compliance. Advanced ventricular deformation impacts the extent of functional recovery benefits achieved through transcatheter aortic valve implantation. Methods and Results: Subgroups were stratified based on output, with low-flow severe aortic stenosis defined as stroke volume index <35 mL· m-2. Before intervention, the low-flow subgroup exhibited worse effective orifice area index and arterial and global impedance, along with thinner wall thickness and larger chamber volume marginally. LV performance, including stroke volume index, ventricular elastance, and ventricular-arterial coupling, were notably inferior, consistent with worse adverse remodeling. Although the effective orifice area index was similarly augmented after TAVI, inferior recovery benefits were noted. Persistently higher wall stress and energy consumption were observed, along with poorer ventricular-arterial coupling. These changes in wall stress showed an inverse relationship with alterations in wall thickness and were proportional to changes in dimension and volume. Additionally, they were proportional to changes in left ventricular end-systolic pressure, pressure-volume area, and ventricular-arterial coupling but inversely related to ventricular end-systolic elastance. Conclusions: The study revealed that aortic valve enlargement through transcatheter aortic valve implantation reduces left ventricular wall stress in severe aortic stenosis. The reduced recovery benefits in the low-flow subgroup were evident. Wall stress could serve as a marker of mechanical benefit after the intervention.

Mechanisms maintaining right ventricular contractility-to-pulmonary arterial elastance ratio in VA ECMO: a retrospective animal data analysis of RV–PA coupling

BackgroundTo optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO.MethodsIn 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance.ResultsAt no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; − 0.1 [− 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; − 0.2 [− 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001).ConclusionsThe right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular–arterial coupling during VA extracorporeal membrane oxygenation.

NON-INVASIVE ASSESSMENT OF HEMODYNAMIC FORCES AND PRESSURE-VOLUME RELATION ANALYSIS IN TWIN PREGNANCY

Objective: This aim of the study was to prospectively investigate pattern of intraventricular Hemo-Dynamic Forces (HDF) associated with Left Ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Design and method: Prospective, cohort study. Transthoracic echocardiography was performed on 35 women (aged 35.9±4.7 years) during gestation (&lt;14 w, T1; 14–27 w, T2; &gt;28 w, T3), and 6–7 months after delivery (T0). LV HDF were computed from echocardiography long axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S/A-B HDF ratio). Results: At T1, L-S/A-B HDF ratio was higher than in T0 (p&lt;0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of Global Longitudinal Strain (GLS) and left ventricular End-Systolic Elastance (Ees) at pressure-volume relationship analysis versus T1 (both p&lt;0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the End Diastolic Pressure-Volume Relationship (EDPVR) with an increase of ventricular capacitance were documented. Conclusions: In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggests the role of HDF in cardiac remodelling.

Effect of age and gender on ventricular-arterial coupling estimated using a non-invasive technique

BackgroundLeft ventricular-arterial coupling is assessed as the ratio of left ventricular end-systolic elastance (Ees) to arterial elastance (Ea). Previous studies have introduced non-invasive estimations of Ees/Ea. It requires only four variables, namely pre-ejection period, ejection time, end-systolic pressure and diastolic pressure. The aims of the present study were to clarify the reference values of Ees/Ea estimated using the noninvasive technique, and to investigate the effects of age and gender on Ees/Ea in healthy subjects.MethodsThis retrospective study utilized data from healthy, 30-79-year-old subjects. We recorded electrocardiogram, phonocardiogram, and brachial arterial pulse waves simultaneously using the vascular screening system, and used the observed variables to calculate Ees/Ea. We separated subjects into five groups according to their age and compared Ees/Ea among the different age groups.ResultsThe study included 2114 males and 2292 females. Ees/Ea ranged from 1.87 to 2.04 in males, and 1.98 to 2.32 in females. We observed no age-related differences in Ees/Ea in males (p = 0.10), and significant differences in females (p < 0.001). Ees/Ea in males was not different compared to those in females in 60-69-year-old group (p = 0.92). Whereas Ees/Ea was higher in females compared to those in males in the other age groups. The differences between medians of Ees/Ea in males and those in females were 0.45 (p < 0.001), 0.24 (p < 0.001), 0.13 (p = 0.01), and 0.13 (p = 0.03) in 30–39, 40–49, 50–59, and 70-79-year-old age groups, respectively.ConclusionsWe clarified the reference values of Ees/Ea in healthy subjects. The effect of age on Ees/Ea is different in males and females, although Ees/Ea is maintained within a relatively narrow range in all subjects.

Left Ventricular-Arterial Coupling as an Independent Predictor of Adverse Events in Young Patients with ST Elevation Myocardial Infarction-A 3D Echocardiographic Study.

Left ventricular-arterial coupling (VAC) is a key determinant of global cardiovascular performance, calculated as the ratio between arterial elastance (EA) and left ventricular end-systolic elastance (EES). Over the years, acute myocardial infarction (STEMI) has remained an important cause of morbidity and mortality worldwide. Although, until recently, it was considered a disease occurring mostly in older patients, its prevalence in the young population is continuously rising. In this study, we aimed to investigate the role of 3D VAC and its derived indices in predicting adverse outcomes in young patients with STEMI. We prospectively enrolled 84 young patients (18-51 years) with STEMI who underwent primary PCI and 28 healthy age and sex-matched controls. A 3D echocardiography was used for non-invasive measurements of end-systolic elastance (EES), arterial elastance (EA), and VAC (EA/EES). The occurrence of major adverse cardiac events (MACE) was assessed one year after the index STEMI. Out of 84 patients, 15.4% had adverse events at 12 months follow-up. Patients were divided into two groups according to the presence or absence of MACE. There were no significant differences in arterial elastance between the two groups. EA was higher in the MACE group but without statistical significance (2.65 vs. 2.33; p = 0.09). EES was significantly lower in the MACE group (1.25 ± 0.34 vs. 1.91 ± 0.56. p < 0.0001) and VAC was higher (2.2 ± 0.62 vs. 1.24 ± 0.29, p < 0.0001). ROC analysis showed that VAC has a better predictive value for MACE (AUC 0.927) compared with EA or EEA but also compared with a classical determinant of LV function (LVEF and LVGLS). A VAC value over 1.71 predicts unfavourable outcome with 83.3% sensitivity and 97.1% specificity. In both univariate and multivariate COX regression analysis, VAC remained an independent predictor for MACE and demonstrated incremental prognostic value over LVEF and LVGLS in the proposed statistical models. In conclusion, 3D VAC is an independent predictor of adverse events in young patients with STEMI at a 12 month follow-ups and could be used for a more accurate risk stratification in the acute phase.

Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Effects of ventricular assist device with a fenestration in the failing Fontan circulation: a theoretical analysis using a lumped parameter model

Abstract Background Fenestration is surgically created at the time of Fontan operation, in which the extracardiac conduit is connected to the atrium through a small communication. Since the fenestration has been reported to increase venous return to the ventricle and improve the hemodynamics, the fenestration is often made when the risk of postoperative Fontan failure is high. In the failing Fontan circulation, the implantation of ventricular assist device (VAD) is sometimes required as a bridge-to-transplantation therapy. However, it has been controversial whether a closure of fenestration is necessary or not. Purpose To evaluate the effects of fenestration on the hemodynamics under VAD in the failing Fontan circulation. Methods A computational model of Fontan circulation was developed using a time-varying elastance cardiac chamber model and a modified 3-element Windkessel vasculature model. Pressure gradient through fenestration was calculated by the simplified Bernoulli’s equation. The relationship between pressure head and rotational frequency of VAD was modeled as a non-linear function. To simulate Fontan failure, ventricular end-systolic elastance was set at 1.0 mmHg/ml and then pulmonary vascular resistance index (PVRI) was varied from 3.0 to 6.8 WU m². Results In the Fontan failure model with PVRI of 3.0 WU m², mean blood pressure (MBP), cardiac index (CI) and central venous pressure (CVP) were 58.4 mmHg, 1.7 l/min/m² and 19.2 mmHg, respectively. When MBP was maintained at the same value, the 4-mm fenestration rarely affected CI (1.7 l/min/m²) and CVP (18.1 mmHg), but significantly decreased oxygen saturation (SpO2, 84.0 %). The introduction of VAD at 4000 rpm significantly increased MBP and CI in both models with/without fenestration (Fenestration (+): 93.7 mmHg, 3.2 l/min/m², Fenestration (-): 94.5 mmHg, 3.2 l/min/m²). In the model with fenestration, SpO2 recovered to 91.6 % after the VAD initiation. However, CVP slightly changed after the VAD initiation in both models with/without fenestration (18.5 and 18.9 mmHg, respectively). When stressed blood volume (SBV) was decreased until end-systolic ventricular volume became around 0 ml, CVP was decreased to the normal range (Fenestration (+): 8.3 mmHg, Fenestration (-): 10.0 mmHg). Then SBV was significantly lower in the model with fenestration than that without fenestration (-150 ml). The effects of fenestration on CVP and SBV were larger in the model with high PVRI of 6.8 WU m² (CVP: -5.5 mmHg, SBV: -460 ml) than those with PVRI of 3.0 WU m² (CVP: -1.7 mmHg, SBV: -150 ml). Conclusions Although fenestration decreases SpO2 at the onset of Fontan failure, fenestration can significantly decrease CVP and SBV under VAD support. These effects are more significant in the patients with higher PVRI. This study demonstrates that fenestration did not impair the hemodynamics under VAD support, indicating the closure of fenestration may not be necessary.

Treatment with sacubitril/valsartan and improvement of ventricular-arterial coupling in heart failure with reduced ejection fraction

Abstract Background Treatment with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) in patients with heart failure and reduced ejection fraction (HFrEF) reduces mortality and heart failure (HF) hospitalizations. The specific hemodynamic mechanisms underlying these beneficial effects are currently unclear. Purpose This study aimed to assess the effects of S/V treatment on left ventricular (LV) end-systolic elastance (Ees), effective arterial elastance (Ea), and the ventricular-arterial coupling ratio (Ea/Ees) in patients with HFrEF using non-invasive pressure-volume analysis. Methods 117 patients with symptomatic HF and LVEF &amp;lt;40% in whom treatment with S/V was initiated were enrolled in this multicenter German prospective study. We used transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements for non-invasive pressure-volume loop analyses. Primary endpoints were changes in Ees, Ea, and Ea/Ees ratio after six months of S/V treatment. Results The mean age was 65 (±13) years and 30% were female. In 54.7% of the patients, the etiology of HF was ischemic, and 45.3% was non-ischemic. 58.4% had first HF diagnosis at baseline. 102 patients with complete clinical and echocardiographic data at baseline and after six months of follow-up were analyzed. Among those, 62% were on target dose of S/V. Six months of S/V treatment resulted in a significant increase of Ees (0.66 mmHg/ml, IQR [0.45;0.94] vs. 0.78 mmHg/ml [0.57;1.10], p=0.001) and decrease of Ea (1.76 mmHg/ml [1.48;2.13] vs. 1.62 mmHg/ml [1.36;1.96], p=0.014). Hence, the Ea/Ees ratio significantly improved (2.52 [1.88;4.05] vs. 1.93 [1.50;2.63], p&amp;lt;0.001). In addition, LV volumes and pressure improved significantly with a regression of the LV end-systolic volume (LVESV: 142 ml [115;180] vs. 96 ml [65;124]), end-diastolic volume (LVEDV: 216 ml [179;247] vs. 165 ml [132;200]) and LV end-diastolic pressure (LVEDP: 19.6 mmHg [18.2;22.4] vs. 17.8 mmHg [16.6;19.9]), p&amp;lt;0.001 respectively. The LVEF increased from a median of 33% (27;37) to 43% (36;49), p&amp;lt;0.001. NT-proBNP level decreased from (median) 1771 pg/ml [838;5211] to 724 pg/ml [300;1575] and mean 6-minute walking distance increased from 371m (±125) to 423 m (±122), p&amp;lt;0.001 respectively. The percentage of patients with NYHA class III changed from 25.6% to 5.9%. Conclusion In a 6-months treatment period, initiation of sacubitril/valsartan in patients with heart failure and reduced ejection fraction was associated with reduction of LV volumes, improved LV function, reduction in afterload and fewer heart failure symptoms. These new data indicate that beyond reverse LV remodeling, improvement of LV contractility and ventricular-arterial coupling may contribute to the favorable clinical outcomes on treatment with sacubitril/valsartan in chronic heart failure.

A Novel Index System for Assessing Ventricular-Vascular Coupling.

To explore the value of a novel ventricular-vascular coupling index (VVI) system in relation to age, gender and body mass index (BMI). A total of 239 volunteers with single-center and cross-sectional health screening were enrolled in the study. Subjects were divided according to age (young [18-44 years], middle-age [45-59 years], old [60-80 years]), gender (male, female), and BMI (overweight/obese [BMI 24], control [BMI 24]). The left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) provided the left ventricular structure index, while the TDI provided the functional index. Also derived from routine echocardiography were the effective arterial elastance (Ea), left ventricular end-systolic elastance (Ees), and VVI. The novel VVI systems were arterial velocity pulse index (AVI), left ventricular global longitudinal strain (LVGLS), and the AVI to LVGLS ratio (AVI/LVGLS). (1) Middle-age and elderly subjects had higher Ea and lower LVGLS compared to young subjects. AVI and AVI/LVGLS increased progressively from young to middle-age to old subjects. (2) Females had higher Ea, Ees and LVGLS than male subjects. No significant differences in AVI and AVI/LVGLS were observed between males and females. (3) No significant differences in Ea, Ees, VVI, AVI, LVGLS and AVI/LVGLS were observed between the overweight/obese and control groups. (4) AVI/LVGLS was negatively correlated with LVEDV and LVESV and with TDI . LVEDV, LVESV and TDI were independent predictors of AVI/LVGLS. (5) The diagnostic performance of AVI/LVGLS was higher than that of VVI in the young and middle-age groups. The diagnostic efficacy of AVI/LVGLS was higher than that of VVI in the young and old groups, and the diagnostic efficacy of AVI was higher than that of Ea. The difference in diagnostic efficacy between LVGLS and Ees was not statistically significant. The differences in diagnostic efficacy between AVI/LVGLS and VVI, AVI and Ea, and LVGLS and Ees were not statistically significant in the middle-age and old groups. The novel index system of ventricular-vascular coupling described here (AVI, LVGLS, and AVI/LVGLS) was more effective than traditional indexes in detecting differences in cardiovascular function between different ages groups. The study protocol was registered on the official website of China Clinical Trial Registration Center (ChiCTR2000035937).

Inverse ESPVR Estimation with Singularity Avoidance via Constrained EDPVR Parameter Optimization.

Left ventricular end-systolic elastance Ees, as an index of cardiac contractility, can play a key role in continuous patient monitoring during cardiac treatment scenarios such as drug therapies. The clinical feasibility of Ees estimation remains challenging because most techniques have been built on left ventricular pressure and volume, which are difficult to measure or estimate in the regular ICU/CCU setting. The purpose of this paper is to propose and validate a novel approach to estimate Ees, which is independent of left ventricular pressure and volume. Our methods first derive an analytical representation of Ees as the inverse function of the gradient of the Frank-Starling Curve based on cardiac mechanics. Second, elucidating the mechanism of singularities in the inverse function, we derive multiple conditions in both end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR) parameters to avoid these singularities analytically. Third, we formulate a constrained nonlinear least squares problem to optimize both ESPVR and EDPVR parameters simultaneously to avoid singularities. The effectiveness of the proposed method in avoiding singularities was evaluated in an animal experiment. Compared to the conventional Ees estimation by linear regression, our proposed method reproduced in-vivo hemodynamics more accurately when simulating the estimated Ees variation during drug administration. Our method can be applied using the available data in the regular ICU/CCU setting. The improved clinical feasibility can support not only physicians' decision-making, including adjusting drug dosages in current clinical treatment, but also a closed-loop hemodynamic control system requiring accurate continuous Ees estimation.

Ventriculo-Arterial Coupling for Predicting Cardiac Index Increase in Infants after Heart Surgery.

To test the ability of ventriculo-arterial coupling to predict cardiac index response after milrinone infusion. This was a retrospective, observational study. We measured arterial blood pressure and echocardiography-derived variables, including cardiac index, systemic vascular resistance index, arterial elastance, and end-systolic ventricular elastance before and after 18-24 hours of milrinone infusion. Ventriculo-arterial coupling was calculated as the ratio of arterial elastance to end-systolic elastance. Infants with over 15% increase in the cardiac index were defined as cardiac index responders. Logistical regression was used to evaluate predictors of cardiac index responders. We enrolled 92 infants who underwent cardiac surgery and received milrinone infusion, of which 45 infants were cardiac index responders. High ventriculo-arterial coupling (odds ratio= 5.534, 95% confidence interval 2.339 to 13.090) and high arterial elastance (odds ratio= 3.035, 95% confidence interval 1.459 to 6.310) were independently associated with cadiac index responders. Pre-milrinone ventriculo-arterial coupling predicted cardiac index responsiveness with a cutoff value of 1.12 (area under the curve = 0.900, 95% CI [0.819 to 0.953], p < 0.0001). Furthermore, we observed a decrease in the infant's ventriculo-arterial coupling, arterial elastance, and systemic vascular resistance index after milrinone infusion. In infants with congenital heart disease after surgery, a pre-milrinone ventriculo-arterial coupling greater than 1.12 can predict the increase in the cardiac index following milrinone infusion.

PS-BPC05-10: DIASTOLIC DYSFUNCTION, HYPERTROPHY AND HYPERTENSION VENTRICULAR-ARTERIAL UNCOUPLING TREATMENT

Objective: the aim of this study was to evaluate the effects of hypertension ventricular-arterial uncoupling treatment on left ventricular hypertrophy and diastolic dysfunction regression. Design and method: observational prospective study, consecutive hypertension patients. Left ventricle mass index measured by Devereux 2D echocardiography method and diastolic function by conventional and tissue Doppler following the Guidelines from Echocardiography from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Left ventricular end systolic elastance (Ees) was measured by Guarracino calculator, the effective arterial elastance (Ea) and ventricular-arterial coupling (VAC) measured by Sunagawa et al single beat method adapted by Chen et al in human ventricles. The sample was analyzed in quartiles (Q) according to VAC (Q1 worst VAC to Q4 best VAC). Follow-up 2 years. Results: 288 patients, mean age 56.3 + 12.5 years and 168 patients (58.3%) males. VAC increased from 0.303 + 0.07 to 0.54 + 0.25 (p &lt; 0.005) in Q1 mainly due to a reduction in Ees from 5.25 + 2.3 to 3.68 + 0.25 mm Hg/ml (p &lt; 0.01) while Ea increased from 1.5 + 0.53 to 1.64 + 0.56 mm Hg/ml (p = NS); on the other side VAC was reduced from 0.87 + 0.15 to 0.68 + 0.26 (p &lt; 0.05) in Q 4 with an increase in Ees from 2.28 + 0.6 to 2.67 + 1.07 mm Hg/ml (p = NS) and a reduction of Ea from 1.94 + 0.41 to 1.69 + 0.67 mm Hg/ml (p = NS) (Figure). The frequency of LVH was reduced from 31.9% to 10.8% in Q1 (p &lt; 0.025) while moved from 14.7 to 17.9% (p = NS) in Q2, 22.9% to 13.9% (p = NS) in Q3 and 11.3 % to 23.7% (p = NS) in Q4. The frequency of normal diastolic function increased from 75% to 94.6% (p &lt; 0.01) in Q1, from 78.7% to 100% in Q2 (p &lt; 0.005), from 87.1% to 100% (p &lt; 0.025) in Q3 and from 88.7% to 100% (0,025) in Q4. Conclusions: 1) patients with the worst ventricular-arterial uncoupling (Q1) are the most VAC benefited from hypertension treatment; 2) regression of left ventricular hypertrophy was observed only in the group of patients with the worst ventricular-arterial uncoupling (Q1); 3) improvement in diastolic function was demonstrated in all Q of ventricular-arterial coupling. This study shows that achieving an optimal mechanical efficiency measured as ventricular-arterial coupling by hypertension treatment is essential for left ventricular hypertrophy and diastolic dysfunction regression.