Left Ventricular End-systolic Elastance Research Articles

Elastic properties of ascending aorta and ventricular–arterial coupling in women with previous pregnancy complicated by HELLP syndrome

To compare the elastic properties of the ascending aorta and ventricular-arterial coupling (VAC) in women with a previous pregnancy complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, women who experienced preeclampsia, and healthy controls. Women with a history of preeclampsia (n = 60) or HELLP syndrome (n = 49) and matched healthy controls (n = 60) underwent transthoracic echocardiography at 6 months to 4 years after delivery. Aortic M-mode and tissue Doppler imaging (TDI) parameters were measured. Aortic diameters were assessed at end-diastole at four levels: Valsalva sinuses, sinotubular junction, tubular tract, and aortic arch. Aortic compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse-wave velocity, and M-mode strain were calculated using standard formulae. Aortic expansion velocity, early and late diastolic retraction velocities, and peak systolic tissue strain (TDI-ε) were determined. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). All women were free from cardiovascular risk factors. Women with a history of HELLP syndrome showed larger aortas than those with previous preeclampsia or controls, probably related to a higher blood pressure. Aortic elastic properties, including Ea, were similar between HELLP and preeclampsia groups, even comparing cases with early-onset preeclampsia and HELLP. In contrast, Ees was more impaired in the HELLP group than in the other two. Consequently, about one-quarter of women who experienced HELLP syndrome had a pathological VAC, whereas only 5% of previously preeclamptic patients did. Multivariate analysis confirmed the association between HELLP syndrome and VAC, whereas other parameters including aortic compliance, distensibility, stiffness index, and elastic modulus are linked only to gestational age at preeclampsia onset, ad also Ea and Ees did. We found a significant overlap between the aortic elastic properties in women with a history of preeclampsia and those with a previous HELLP syndrome, suggesting a common pathophysiologic pathway. However, women who experienced HELLP syndrome showed a higher blood pressure than other cases and controls, probably determining larger aortas. In addition, VAC was more altered in the HELLP group than in the others because of a higher Ea and a lower Ees.

Left ventricular end-systolic volume is a more sensitive marker of acute response to cardiac resynchronization therapy than contractility indices: insights from an experimental study.

There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

A13994 Blood pressure variability and hypertensive target organ damage

Objectives: to investigate an impact of blood pressure variability (BPV) on heart and brain hypertensive damage in the middle-aged untreated patients with grade 1–2 essential arterial hypertension (EAH) without concomitant cardiovascular diseases. Methods: we examined 60 naive hypertensive patients (HP) with EAH and 44 sex- and age-matched healthy individuals. Comprehensive transthoracic echocardiography (Vivid 7 Dimension, GE) with 2D speckle tracking analysis and ambulatory blood pressure monitoring were performed in all participants. BPV was estimated as standard deviation. 41 HP underwent brain magnetic resonance imaging (MAGNETOM Skyra 3.0T, Siemens AG). Fazekas scale was used to quantify the amount of white matter hyperintensities (WMH). Results: nighttime systolic BPV (sBPV) and nighttime diastolic BPV (dBPV) were significantly (p < 0,001 for all) higher in HP (12,1 ± 0,1 vs. 9,3 ± 0,4 mmHg in controls and 9,8 ± 0,4 vs. 6,9 ± 0,3 mmHg in controls, respectively). Correlation analyses in HP revealed significant association of nighttime sBPV with left ventricular (LV) end-systolic elastance (r = −0,375; p < 0,01) and LV end-diastolic stiffness (r = −0,429; p < 0,01). Daytime dBPV significantly correlated with LV diastolic elastance (r = 0,265; p < 0,05), nighttime dBPV - with left atrial expansion index (r = −0,282; p < 0,05). WMH (Fazekas 1 and 2) were found in 53,7% HP patients. In HP with WMH 24 hours sBPV (19,7 ± 3,9 mmHg) and daytime sBPV (18,0 ± 4,5 mmHg) were significantly (p < 0,05 for all) higher compared to same parameters in HP without WMH (17,2 ± 3,3 and 15,7 ± 3,1 mmHg, respectively). Conclusion: middle-aged untreated patients with grade 1–2 uncomplicated EAH are different from the sex- and age-matched healthy individuals by higher nighttime BPV. BPV associated with heart and brain hypertensive organ damage.

Intravenous Infusion of the Novel HNO Donor BMS-986231 Is Associated With Beneficial Inotropic, Lusitropic, and Vasodilatory Properties in 2 Canine Models of Heart Failure

The effects of the nitroxyl donor BMS-986231 on hemodynamics, left ventricular (LV) function, and pro-arrhythmic potential were assessed using canine heart failure models. BMS-986231 significantly (p< 0.05) increased LV end-systolic elastance, pre-load-recruitable stroke work, ejection fraction, stroke volume, cardiac output, ratio of early-to-late filling time integrals, and early mitral valve inflow velocity deceleration time. BMS-986231 significantly decreased LV filling pressures, end-diastolic stiffness, the time-constant of relaxation, end-diastolic wall stress, systemic vascular resistance, and myocardial oxygen consumption. BMS-986231 had little effect on heart rate and did not induce de novo arrhythmias. Thus, BMS-986231 has beneficial inotropic, lusitropic, and vasodilatory effects.

Ventricular-Vascular Coupling at Rest and after Exercise Is Associated with Heart Failure Hospitalizations in Patients With Coronary Artery Disease

The ventricular-vascular coupling ratio, defined as the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has not been examined in populations with coronary artery disease (CAD), and its association with heart failure (HF) in this population is unknown. Ventricular-vascular coupling was measured at rest and after exercise using echocardiography and cuff blood pressure in 815 patients with stable CAD enrolled in the Heart and Soul Study. Adjusted Cox proportional-hazard models were used to evaluate the association between ventricular-vascular coupling and future HF hospitalizations. After a median of 8.9years, 144 patients (18%) were hospitalized for HF. After multivariate adjustment, patients in the highest tertile of Ees (rest: hazard ratio [HR], 0.31 [95% CI, 0.17-0.57; P<.001]; exercise: HR, 0.26 [95% CI, 0.13-0.50; P<.001]) were at decreased risk for HF hospitalization, while patients in the highest tertile of the Ea/Ees ratio (rest: HR, 3.36 [95% CI, 1.91-5.93; P<.001]; exercise: HR, 4.09; [95% CI, 2.22-7.51; P<.001]) were at increased risk, compared with the lowest tertiles. Ea and the relative change observed in Ees and the Ea/Ees ratio with exercise were not associated with HF hospitalizations. The Ea/Ees ratio and Ees, at rest and after exercise, are strongly associated with future HF hospitalizations in patients with stable CAD and low rates of baseline HF. Ventricular-vascular coupling obtained from echocardiography shows promise as a risk assessment tool for HF in patients with CAD.

Estimating Left Ventricular Elastance from Aortic Flow Waveform, Ventricular Ejection Fraction, and Brachial Pressure: An In Silico Study.

Although left ventricular end-systolic elastance (Ees) serves as a major index of cardiac contractility, a widely-accepted noninvasive estimation of Ees does not exist. To overcome this limitation, we developed a two-step inverse method that allows for its noninvasive estimation from measurements of aortic flow and brachial pressure using a previously validated one-dimensional model of the cardiovascular system. In a first step, aortic flow is set as the model input and the output brachial pressure is compared with the "real" values. Subsequently, the basic properties of the arterial tree are tuned according to an optimization algorithm. In a second step, the same optimization method is used to estimate the elastance parameters that produce an aortic flow waveform that matches the "real" one. Additional knowledge of the ejection fraction can allow for the accurate estimation of the entire P-V loop, including end-diastolic elastance. The method was tested on a database of 50 different in silico hemodynamic cases generated after varying cardiac and arterial model parameters. Implementation of the method yielded good agreement (r = 0.99) and accuracy (n-RMSE = 4%) between "real" and estimated values of Ees. Furthermore, a sensitivity analysis revealed that errors due to poor arterial adjustment and measurements are small (≤ 8% for Ees).

MYOCARDIAL STIFFNESS AND LEFT VENTRICULAR HYPERTROPHY IN THE MIDDLE-AGED HYPERTENSIVE PATIENTS

Objective: to investigate left ventricular (LV) and left atrial (LA) stiffness parameters in middle-aged patients with grade 1–2 essentiial arterial hypertension (EAH) without concomitant cardiovascular diseases according to the presence of LV hypertrophy (LVH). Design and method: Case-control study. We examined 127 naive patients with uncomplicated grade 1–2 EAH and divided them into two groups according to the LV mass index (LVMI). The first one is included 96 hypertensive patients (HP) with LVH (mean LVMI 125,8 ± 2,1 g/m2, mean age 52,6 ± 0,7 years; mean office blood pressure (BP) 151,9 ± 1,5/93,8 ± 1,1 mm Hg). The second group consisted of 31 patients without LVH (mean LVMI 89,7 ± 2,1 g/m2, mean age 51,3 ± 1,0 years; mean office BP 138,7 ± 2,1/83,5 ± 1,9 mm Hg). 44 healthy individuals (mean age 51,5 ± 1,0 years; mean office BP 120,1 ± 2,0/80,5 ± 1,0 mm Hg) represented the control group. All the patients underwent 24-hours ambulatory BP monitoring. Comprehensive transthoracic echocardiography using Vivid 7 Dimension system (GE) was also performed. LV end-diastolic stiffness, LV end-systolic elastance, LV diastolic elastance, LA stiffness index, LA expansion index and tissue Doppler-derived (TDD) LA strain were calculated. 2-D speckle tracking echocardiography data were acquired for determination of LV myocardial global longitudinal peak strain (LV GLPS). Results: TDD LA strain was significantly higher in HP without LVH (60,01 ± 4,77%) compared to HP with LVH (49,77 ± 1,49%; p < 0,05). LV GLPS was significantly lower in absolute value in HP with LVH (−16,9 ± 0,3%) and HP without LVH (−17,5 ± 0,6%) compared to controls (−19,9 ± 0,4%; p < 0,001 and p < 0,01, respectively). No significant differences between studied groups were obtained in other myocardial stiffness parameters. LV GLPS showed a weak but significant associations with office diastolic BP (r = 0,354; p < 0,01), 24 h systolic BP (r = 0,291; p < 0,05), 24 h pulse pressure (r = 0,296; p < 0,05), and average night-time systolic and diastolic BP (r = 0,343; p < 0,01 and r = 0,262; p < 0,05, respectively). Conclusions: the present study reveals that disturbances in myocardial stiffness parameters occur early, before the development of echocardiographic signs of LHV. They are earlier markers of target organ damage even in middle-aged untreated patients with grade 1–2 uncomplicated EAH.

MYOCARDIAL STIFFNESS IN THE MIDDLE-AGED HYPERTENSIVE PATIENTS IN THE PRESENCE OF OVERWEIGHT OR OBESITY

Objective: to evaluate left ventricular (LV) and left atrial (LA) stiffness parameters in middle-aged patients with arterial hypertension grade 1–2 without concomitant cardiovascular diseases in terms of the presence of overweight or obesity. Design and method: Case-control study. We examined 127 naive patients with uncomplicated essential arterial hypertension grade 1–2 and divided them into three groups in accordance with body mass index (BMI) values. The first one is included 19 patients with normal weight - mean BMI 23,2 ± 0,2 kg/m2, mean age 50,6 ± 1,0 years; 7 men; mean office blood pressure 142,1 ± 3,6/ 83,2 ± 2,5 mm Hg). The second group consisted of 52 patients with overweight - mean BMI 28,0 ± 0,2 kg/m2, mean age 53,1 ± 1,0 years; 26 men; mean office blood pressure 147,9 ± 2,0/ 90,9 ± 1,5 mm Hg). And the third group is included 56 patients with obesity - mean BMI 34,2 ± 0,4 kg/m2, mean age 52,0 ± 0,8 years; 33 men; mean office blood pressure 151,7 ± 2,0/ 94,4 ± 1,5 mm Hg). Comprehensive transthoracic echocardiography using Vivid 7 Dimension system (GE) were performed. LV end-diastolic stiffness, LV end-systolic elastance (ESE), LV diastolic elastance, LA stiffness index, LA expansion index and tissue Doppler-derived LA strain were calculated. 2-D speckle tracking echocardiography data were acquired for determination of LV myocardial global longitudinal peak strain (LV GLPS). Results: LV GLPS was significantly (p < 0,001) lower in absolute value in patients with obesity (−15,6 ± 0,4%) compared with overweight group (−18,0 ± 0,4%) and the patients with normal weight (−18,5 ± 0,5%). LV ESE was significantly lower in patients with obesity (3,75 ± 0,13 mm Hg/ml) compared with overweight persons (4,34 ± 0,16 mm Hg/ml; p < 0,05) and the patients with normal weight (4,81 ± 0,26 mm Hg/ml; p < 0,001). No significant differences between studied groups were obtained in other myocardial stiffness parameters. Conclusions: The present study reveals that obesity leads to increased LV myocardial stiffness in untreated middle-aged patients with uncomplicated arterial hypertension grade 1–2 in comparison with sex-, age- and hypertension history-matched patients with overweight or normal BMI.

Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs.

Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen demand, thereby reducing infarct size and preventing subsequent heart failure. In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P<0.001), increased LV end-systolic elastance (4.3±0.8 versus 13.9±5.1 mm Hg/mL; P<0.001), and decreased NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (4081±1123 versus 1773±390 pg/mL; P<0.05). Furthermore, total support markedly reduced infarct size relative to I/R, whereas partial support decreased infarct size to a lesser extent (I/R, 16.3±2.6; partial support, 8.5±4.3; and total support, 2.1±1.6%; P<0.001). LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.

Adiposity, body composition and ventricular-arterial stiffness in the elderly: the Atherosclerosis Risk in Communities Study.

Weight gain appears to accelerate age-related ventricular-arterial stiffening, which has been implicated in the development of heart failure (HF), but it is unclear whether body fat accumulation underpins this association. We evaluated the relationship of adiposity, using measures of body composition, with ventricular-arterial stiffness among the elderly in the community. Adiposity was accessed through body mass index (BMI), waist circumference, and body fat percentage. We studied the association of these measures with carotid-femoral pulse wave velocity (cfPWV), arterial elastance index (EaI), left ventricular (LV) end-systolic elastance index (EesI) and LV end-diastolic elastance index (EedI) in 5520 community-based, elderly Atherosclerosis Risk in Communities (ARIC) Study participants, who underwent echocardiography between 2011 and 2013. BMI and waist circumference were directly associated with EaI, EedI and EesI even after adjusting for age, sex, race, hypertension, diabetes mellitus, heart rate, prevalent coronary heart disease and HF. After further adjustment for BMI, body fat percentage demonstrated significant independent linear relationships with EaI [standardized beta coefficient (β)=0.17, P<0.001], EesI (β=0.08, P=0.003) and EedI (β=0.20, P<0.001), and significant non-linear relationships with cfPWV (P=0.033). In this biracial community-based cohort, increased adiposity was associated with increased ventricular-arterial stiffness among the elderly and suggests a potential mechanism by which obesity might contribute to the development of HF.

Ventricular‐arterial Coupling in Prostate Cancer Patients Treated with Androgen Deprivation Therapy at Rest and During Exercise

IntroductionAndrogen‐deprivation therapy (ADT) in prostate cancer has been suggested to promote an unfavorable cardiovascular disease risk profile and long‐term cardiovascular mortality. Impairments in vascular structure (increased arterial stiffness) and function (decreased endothelial‐dependent dilation) are known to occur with ADT, however, it remains unknown if the changes in structure‐function relationship adversely impacts the interaction between ventricular and arterial systems. Ventricular‐arterial coupling is a measure of effective arterial elastance (Ea) and left ventricular end‐systolic elastance (Ees) and is a central determinant of cardiovascular performance and cardiac energetics. Therefore, this study sought to evaluate ventricular‐arterial coupling at rest and during submaximal exercise in prostate cancer patients with and without a history of ADT.MethodsTo date, 7 prostate cancer patients with (n=3) and without (n=4) a history of androgen‐deprivation therapy treatment have completed the study. Ea, Ees, and ventricular‐arterial coupling (Ea/Ees) were measured at rest and during supine submaximal exercise. A high Ea/Ees is reflective of a compromised interaction between ventricular and arterial systems. To minimize the effect of heart rate on each parameter submaximal exercise was performed at a work rate corresponding to a heart rate of 100 beats/min.ResultsAt rest Ea (ADT: 2.9±0.2 mmHg/mL; non‐ADT: 3.4±0.8 mmHg/mL; P=0.2), Ees (ADT: 3.2±1.9 mmHg/mL; non‐ADT: 3.6±0.6 mmHg/mL; P=0.2), and Ea/Ees (ADT: 0.79±0.39; non‐ADT: 0.97±0.30; P=0.5) were similar between ADT and non‐ADT groups. Ea was not different between groups during exercise (ADT: 7.0±1.1 mmHg/mL; non‐ADT: 6.6±0.6 mmHg/mL; P=0.3). Moderate‐intensity exercise‐induced increases in Ees trended to be decreased in the ADT group (ADT: 3.5±1.2 mmHg/mL; non‐ADT: 4.7±0.5 mmHg/mL; P=0.05). Ea/Ees was also higher in the ADT group during exercise compared to the non‐ADT group, but did not reach statistical significance (ADT: 0.93±0.16; non‐ADT: 0.77±0.16; P=0.1).ConclusionsThe findings from this study provide preliminary data that indicates ADT in prostate cancer patients may adversely alter left ventricular end‐systolic elastance during exercise, but does not significantly alter ventricular‐arterial coupling. Additional data will contribute to the evaluation of the interaction between ventricular and arterial systems in patients receiving ADT.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Left ventricular remodelling and vascular adaptive changes in adolescents with obesity.

The aim of this study was to determine the effects of obesity on myocardial mechanics and ventriculo-arterial coupling (V-A) in children. Strain parameters, stroke volume, arterial elastance, left ventricular (LV) elastance and V-A were compared after adjusting for age and hypertension and after multivariate sub-group analysis between patients with and without obesity. Among 123 retrospectively enrolled subjects, 6-21years age, 79.7% males, 52% were obese. Median (range) Body Mass Index Z score was +2.35 (1.67-4.43) for obese and +0.68 (-2.48-1.63) for non-obese. Subjects with obesity had higher LV mass indexed2.7 (LVMI2.7 ) compared with non-obese (P<0.001). Lower global longitudinal strain (GLS) (P=0.012), global circumferential strain (GCS) (P=0.004), average longitudinal strain rate (P=0.002) and average circumferential strain rate (P<0.001) were seen in subjects with obesity; no difference was noted in arterial elastance, LV end systolic elastance and V-A. Increased LVMI2.7 , decreased GLS, GCS, average longitudinal strain rate, average circumferential strain rate and maintained V-A were noted in the multivariate analysis between subgroups. Obesity causes alterations in myocardial mechanics with preserved V-A in children. These findings may aid intervention in preventing the long-term cadiovascular effects of obesity.

The relationship between systolic vector flow mapping parameters and left ventricular cardiac function in healthy dogs

Vector flow mapping (VFM) is a novel echocardiographic technology that shows blood flow vectors and vortexes, enabled the hydrokinetic evaluation of hemodynamics within the left ventricle. VFM provides several unique parameters: circulation, vorticity, vortex area, and energy loss. The present study aims to reveal a relationship between VFM parameters and cardiac function. Five healthy Beagle dogs were anesthetized and administered with dobutamine (0, 2, 4, 8, 12µg/kg/min). Pressure-volume diagrams were acquired to assess cardiac function using pressure-volume conductance catheter. Systolic maximum circulation, vorticity, vortex area, and energy loss were measured using VFM. The systolic maximum circulation, systolic vorticity, systolic vortex area, and systolic energy loss were increased by dobutamine administration. There was a strongly significant correlation between the systolic maximum circulation and ejection fraction (r=0.76), maximal positive left ventricular (LV) pressure derivatives (dP/dt max) (r=0.80), and end-systolic LV elastance (r=0.73). Systolic vorticity and systolic vortex area were strongly correlated with ejection fraction (r=0.76, 0.68) and dP/dt max (r=0.76, 0.69), and end-systolic LV elastance (r=0.62, 0.74), respectively. Systolic energy loss was strongly correlated with dP/dt max (r=0.78), systolic maximum circulation (r=0.81), and systolic vorticity (r=0.82). The present study revealed that systolic VFM parameters are associated with the LV contractility. Furthermore, systolic energy loss was susceptible to the systolic vortex parameters such as systolic vorticity and systolic maximum circulation. Systolic VFM parameters are new hydrokinetic indices reflecting LV contractility.

Ventricular-arterial coupling in centenarians without cardiovascular diseases.

Ventricular-arterial (VA) coupling is a central determinant of cardiovascular system performance and cardiac energetics. This index is expressed by the Ea/Ees ratio, where the effective arterial elastance (Ea) indicates the net arterial load exerted on the left ventricle and the left ventricular end-systolic elastance (Ees) is a load-independent measure of left ventricular chamber performance. Thirty-three centenarians (100.6 ± 1.2years, range 99-105years, 10M) without cardiovascular diseases underwent a complete echocardiographic evaluation and an instantaneous arterial blood pressure measurement, to characterize the Ea/Ees ratio and its two determinants indexed to body surface area. VA coupling was markedly reduced (Ea/Ees ratio 0.40 ± 0.1), reflecting a disproportionate increase in Ees index (8.5 ± 2.2mmHg/ml/m2) compared with Ea index (3.2 ± 0.8mmHg/ml/m2). Notably, the coupling ratio was significantly lower in women (0.37 ± 0.1) than in men (0.45 ± 0.1, p = 0.0003), due to an increase in Ees index significantly greater in women (9.4 ± 1.9mmHg/ml/m2) than in men (6.5 ± 1.5mmHg/ml/m2, p = 0.0002). Using multivariate regression analysis, only female gender (β coefficient -0.04, p = 0.01) and relative wall thickness (β coefficient -0.49, p < 0.0001) showed a significant inverse correlation to VA coupling. Our analysis in a population of centenarians without overt cardiovascular disease revealed very low values of VA coupling, especially in women. Both a LV structural remodeling as well as a high aortic elastance might have contributed to a secondary disproportionate increase in myocardial stiffness.

Insights into cardiac alterations after pre-eclampsia: an echocardiographic study.

To investigate cardiovascular (CV) performance status several years after early-onset (EO) or late-onset (LO) pre-eclampsia (PE), using echocardiography to assess myocardial strain and left ventricular (LV) torsional mechanics and ventricular-arterial coupling (VAC). Thirty non-pregnant women with a previous singleton pregnancy complicated by EO-PE, 30 who had experienced LO-PE and 30 controls underwent echocardiography with two-dimensional (2D) speckle tracking between 6 months and 4 years after delivery and their findings were compared. All women were free from CV risk factors. VAC was defined as the ratio between aortic elastance (Ea) and LV end-systolic elastance (Ees). Women in the EO-PE group showed a persistent subclinical impairment in LV systole and a slight alteration in right ventricular function, with reductions in LV 2D strain (circumferential, radial and longitudinal) and right ventricular 2D strain and impairment of LV torsional mechanics, when compared both with women in the LO-PE group and with healthy controls. Although VAC was within the normal range in the whole study cohort, its individual components Ea and Ees were significantly altered more often in the EO-PE group than in both the LO-PE group and controls. All parameters investigated (except right ventricular 2D strain) were associated independently with gestational age at the time of diagnosis of PE. Women with a history of EO-PE are more likely to have subclinical impairment of systolic biventricular function than are those with a history of LO-PE and controls. The components of VAC (Ea and Ees) show subclinical alterations which are more significant in women with a history of EO-PE than in those with a history of LO-PE and controls, although VAC itself is maintained. Our study supports the use of closer CV monitoring in previously pre-eclamptic women, particularly those in whom PE was preterm. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effects of Amlodipine/Lisinopril Fixed-Dose Combination on Severity of Left Ventricular Hypertrophy and Parameters of Myocardial Stiffness in Patients With Hypertension

To assess effects of 12 weeks treatment with the amlodipine/lisinopril fixed-dose combination (ALFDC) on the left ventricular (LV) mass index (LVMI), parameters of LV and left atrial stiffness. At phase 1 of the study we examined 44 healthy subjects (21 men, 23 women, mean age 51.5+/-1.0 years) and 60 untreated patients (31 men, 29 women, mean age 53.6+/-0.8 years) with stage II grade 1-2hypertension. Myocardial stiffness parameters, LVMI were calculated using data of transthoracic echocardiography. 2-D speckle tracking echocardiography was used for determination of LV myocardial global longitudinal peak strain (GLPS). All participants underwent ambulatory blood pressure (BP) monitoring, and office BP measurement. At phase 2 a subgroup of 30 untreated patients (16 men, 14 women; mean age 52.7+/-1.11years) received ALFDC in a start dose of 5 mg/10 mg titrated every 14 days to achieve BP<140/90 mm Hg. Therapy in selected doses was continued for 12 weeks thereafter. In hypertensive patients LV GLPS was significantly lower while LA stiffness index higher compared with controls (17.08+/-0.38 vs. 19.91+/-0.41%, p<0.001, and 0.20+/-0.01 vs. 0.16+/-0.01, p<0.01, respectively). There were no significant differences in the LA tissue Doppler derived strain, LV end-systolic elastance, LA expansion index between hypertensive and control groups. After ALFDC therapy BP was significantly (p<0.001) reduced: systolic (S)BP from 154.4+/-2.7 to 130.6+/-1.2, diastolic (D)BP from 96.5+/-1.3 to 83.0+/-0.5 mm Hg. After therapy LV GLPS, LA expansion index, LV diastolic elastance significantly increased (from 17.10+/-0.57 to 18.29+/-0.35%, p<0.01; from 1.47+/-0.08 to 1.68+/-0.08, p<0.001; from 9.25+/-0.99 [10-2] to 10.88+/-1.0 8 [10-2], p<0.05, respectively) while LVMI, LV end-diastolic stiffness, and LA stiffness index significantly (p<0.001) decreased (from 129.4+/-4.5 to 111.8+/-3.3 g/m2, from 0.16+/-0.01 to 0.12+/-0.01 mm Hg/ml, from 0.21+/-0.02 to 0.15+/-0.01, respectively). Change in the LA tissue Doppler derived strain correlated with the change in dynamics of nighttime SBP (r=-0.410, p<0.05). There was direct relationship between change in LV diastolic elastance and nighttime DBP (r=0.424; p<0.05); and an inverse correlation between changes in LV end-diastolic stiffness and dynamics of the daytime SBP and DBP (r=-0.404; p<0.05 and r=-0.364; p<0.05, respectively). Change of LVMI after ALFDC treatment correlated with dynamics of 24-hour, daytime SBP, and daytime pulse pressure (r=0.382, p<0.05, r=0.478, p<0.01, and r=0.364, p<0.05, respectively). In untreated patients with stage II, 1-2 degree hypertension 12-week therapy with ALFDC allowed to achieve target BP levels, reduced severity of LV hypertrophy and improved stiffness parameters of the myocardium.

Ventricular-Arterial Coupling in Severe Aortic Stenosis: Relationship with Symptoms and Heart Failure

Background: Left ventricular function is determined by ventricular-arterial coupling via effective arterial elastance (Ea) and leftventricular end-systolic elastance (Ees). In aortic stenosis, the characteristics of the vascular system may influence left ventricularfunction, particularly in patients with symptoms or heart failure.Objective: The aim of the present study was to evaluate ventricular-arterial coupling using the Ea/Ees ratio in patients with severeaortic stenosis and its relationship with symptoms and heart failure.Methods: The cohort consisted of 136 patients aged 69±11 years, with severe aortic stenosis (aortic valve area <1 cm2). Ea and Eeswere estimated noninvasively. Patients were divided into three groups: heart failure (n=48), symptomatic (n=45) and asymptomatic(n=43).Results: Ea was increased in patients with heart failure while Ees was significantly reduced in patients with symptoms and withheart failure compared with asymptomatic ones. The Ea/Ees ratio was significantly higher in symptomatic and heart failure patientscompared with asymptomatic patients (1.5±1.3 and 0.81±0.49 vs. 0.61±0.37; p<0.01). There were no significant differences inaortic valve area among groups.Conclusions: The Ea/Ees ratio was increased in patients with symptoms or heart failure due to increased Ea and reduced Ees. Thedevelopment of symptoms or heart failure in severe aortic stenosis seems to be related with the characteristics of the vascular system,irrespectively of aortic stenosis severity.

Echo-Doppler-derived indexes of ventricular stiffness and ventriculo-arterial interaction as predictors of new-onset atrial fibrillation in patients with heart failure.

BackgroundAtrial fibrillation (AF) is common in patients with heart failure (HF) and worsens their prognosis. Vulnerability to changes in loading is an important factor in the development of AF and is strongly influenced by ventricular stiffness and ventriculo-arterial interaction. The aim of this study was to investigate predictors of AF development in patients with HF.MethodsWe studied 349 patients with stable HF. The following parameters of ventricular stiffness and ventriculo-arterial interaction were derived from echo-Doppler measurements: left ventricular (LV) diastolic elastance (Ed), effective arterial elastance (Ea), LV end-systolic elastance (Ees) and ventricular–vascular coupling index (VVI).ResultsAF occurred in 57 (16.3 %) patients over a median follow up of 30.3 months. Echo-Doppler–derived parameters of ventricular stiffness and ventriculo-arterial interaction were closely associated with HF severity. Ed was independently associated with AF after adjustment for age, hypertension, diabetes mellitus, and left atrial volume index (hazard ratio [HR] 5.49, p = 0.018). Ea and VVI were also associated with new-onset AF (HR 1.66, p = 0.027, and HR 1.06, p = 0.001, respectively).ConclusionsEcho-Doppler indexes of ventricular stiffness are closely associated with HF severity. LV diastolic elastance (Ed) is the strongest predictor of new-onset AF in HF patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12947-016-0050-y) contains supplementary material, which is available to authorized users.

Abstract 16161: GSK-3β Activates Autophagy and Protects Against Cardiac Aging Through Ulk1

Accumulating lines of evidence suggest that glycogen synthase kinase-3β (GSK-3β) is involved in aging. However, the effects of GSK-3β on cardiac aging and the underlying mechanisms remain to be elucidated. Autophagy, a protective mechanism in aging, decreases with age. We hypothesized that GSK-3β attenuates cardiac aging via Ulk1, a regulator of autophagy, and studied constitutively active GSK-3βS9A knock-in mice (βKI), GSK-3βS9A/Ulk1+/- bigenic mice (Bigenic), and GSK-3β+/- mice (βKO) up to 24 months (M) of age. Left ventricular (LV) weight/body weight (LVW/BW, mg/g) was not significantly different among wild-type mice (WT), βKI and βKO at 6M. It was lower in βKI (2.4±0.1, p&lt;0.005) and higher in βKO (4.8±0.8, p&lt;0.05) than in WT (3.8±0.2) at 24M. Cardiomyocyte cross-sectional area (CSA, μm2) was smaller in βKI (360±9, p&lt;0.001) but bigger in βKO (540±11, p&lt;0.01) than in WT (502±5) at 24M. The LVW/BW was greater (3.5±0.2, p&lt;0.001) and the CSA was bigger (527±4, p&lt;0.001) in Bigenic than in βKI at 24M. These data demonstrate that GSK-3β inhibits age-dependent cardiac hypertrophy via Ulk1. Cardiac fibrosis (%) was more in βKO (5.4±0.1, p&lt;0.001) and less in βKI (2.4±0.1, p&lt;0.001) than in WT (4.0±0.3) at 24M. There was much more fibrosis in Bigenic (5.5±0.6, p&lt;0.001) than in βKI at 24M. These data show that GSK-3β reduces age-related cardiac fibrosis via Ulk1. LV end-systolic elastance (Ees, mmHg/μl) and chamber stiffness constant (CSC, μl-1) were not significantly different among WT, βKI, and βKO at 6M. At 24M, the Ees was lower in βKO (4±1, p&lt;0.05) and higher in βKI (12±3, p&lt;0.05) than in WT (7±0), and the CSC was higher in βKO (0.19±0.01, p&lt;0.001) and lower in βKI (0.06±0.01, p&lt;0.001) than in WT (0.14±0.01). The beneficial effects of GSK-3β on cardiac function were abolished in the Bigenic, indicating that GSK-3β prevents age-specific cardiac dysfunction via Ulk1. The level of p62, a protein degraded by autophagy, was lower in βKI and higher in βKO than in WT. The numbers of autophagosomes and autolysosomes were significantly greater in βKI/tfLC3 (tandem fluorescent mRFP-GFP-LC3) mice than in tfLC3 or βKI/tfLC3/Ulk1+/- mice. These data suggest that GSK-3β activates autophagy via Ulk1. In conclusion, GSK-3β attenuates cardiac aging by activating Ulk1-dependent autophagy.

Abstract 12925: The Neuro-Mechanical Unloading for Acute Myocardial Infarction Strikingly Reduces the Infarct Size and Prevents Heart Failure in the Long Term (Best of Basic Science Abstract)

Introduction: Although widespread practice of early coronary intervention has reduced the acute phase mortality in myocardial infarct (MI), the late development of heart failure remains increasing at an alarming rate. Left ventricular (LV) assist device (VAD) unloads the heart, thereby decreases oxygen consumption. Vagal nerve stimulation (VNS) exerts a powerful anti-infarct effects. Hypothesis: We hypothesized that the combination of short term VAD (mechanical unloading) and VNS (neural unloading) for the ischemia/reperfusion (IR) model would prevent the late development of heart failure. Methods: In 24 dogs, we occluded the left anterior descending coronary artery for 180min and then reperfused. We unloaded LV with transvascular VAD (Impella®). We administrated transvascular VNS with a pacing catheter in the superior vena cava (10Hz). The neuro-mechanical unloading started at 90min after the onset of ischemia and ended at 60min after reperfusion. We allocated dogs into 4 groups, IR (n=7), VAD (n=6), VNS (n=4) and VAD+VNS (n=5) and compared the infarct size and cardiac function one month after IR. Results: LVAD+VNS normalized LV end-systolic elastance (IR: 6.1±3.3, VAD: 8.1±1.3, VNS: 10.6±4.5, VAD+VNS: 14.9±2.8 mmHg/ml, p&lt;0.05) and maximally lowered LV end-diastolic pressure (EDP) (16.8±6.4, 6.4±1.5, 5.3±3.1, 3.7±0.4 mmHg, p&lt;0.05). NT-proBNP paralleled the changes in LVEDP (3712±1141, 1728±348, 1507±511, 1059±397 mmHg, p&lt;0.05), supporting nearly normalized cardiac function. VAD+VNS strikingly reduced the infarct size by more than 70% (p&lt;0.05, Figure). Conclusions: The combination of short term VAD and VNS prior to reperfusion markedly reduces the infarct size and prevents the late development of heart failure. The fact that we can deliver both VAD and VNS transvascularly indicates that the neuro-mechanical unloading therapy is clinically applicable and would improve the long term survival in post-MI patients with coronary intervention.