Changes In Left Ventricular Contractility Research Articles

Early improvement of global longitudinal strain after iron deficiency correction in heart failure with reduced ejection fraction.

Iron deficiency correction with ferric carboxymaltose improves symptoms and reduces rehospitalization in patients with reduced left ventricular ejection fraction. The mechanisms underlying these improvements are poorly understood. This study aimed to determine changes in left ventricular contractility after iron treatment as reflected in global longitudinal strain. Prospective single-center study including 43 adults with reduced ejection fraction, non-anemic iron deficiency, and functional class II-III heart failure despite optimal medical treatment. Global longitudinal strain through speckle-tracking echocardiography was measured at baseline and 4weeks after ferric carboxymaltose. A significant improvement in global longitudinal strain was detected (from -12.3%±4.0% at baseline to -15.6%±4.1%, p<.001); ferritin and transferrin saturation index had increased, but ejection fraction presented no significant changes (baseline 35.7%±4.6%, follow-up 37.2%±6.6%, p=.073). In patients with heart failure and reduced ejection fraction, the correction of iron deficiency with ferric carboxymaltose is associated with an early improvement in global longitudinal strain, possibly suggesting a direct effect of iron correction on myocardial contractility.

The acute hemodynamic effects of sodium lactate infusion: increased cardiac output and decreased afterload in a randomized trial in pigs

Abstract Background Lactate is traditionally acknowledged as a by-product of anaerobic glucose metabolism. Recently, however, lactate has been proven to be a preferred oxidative substrate for stressed myocardium. Studies have shown that exogenous lactate infusion provides beneficial hemodynamic effects including increased cardiac output (CO). Nevertheless, the exact mechanism of action underlying the hemodynamic effects of lactate infusion has not been fully elucidated. Aim To identify the cardiovascular mechanisms behind the acute hemodynamic effects of exogenous sodium lactate infusion in an experimental model of healthy human-sized pigs. Methods We performed a randomized, assessor-blinded crossover study in eight female 60 kg pigs. In randomized order, the pigs received an infusion with 1 M sodium lactate for two hours and a control infusion with iso-osmolar and isovolumetric sodium chloride for two hours. The two infusion periods were separated by a one-hour washout period. We measured CO and pulmonary pressures hourly with a pulmonary artery catheter. A pressure-volume admittance catheter was inserted in the left ventricle to assess measures of cardiac efficiency, contractility, afterload, and preload. Hemodynamic measures as arterial blood pressure, heart rate, and mixed venous saturation (SvO2) were measured hourly as well. The study followed the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and national and European legislations. Results Lactate levels increased by 9.9 mmol/L (95% CI 9.1 to 11.0) and CO increased by 2.0 L/min (95% CI 1.2 to 2.8) during lactate infusion as compared with the control period (figure 1). During lactate infusion, ejection fraction increased by 16.0 percentage points (95% CI 1.9 to 31.0) and heart rate by 21 bpm (95% CI 9 to 32) compared with control. Arterial elastance decreased by -1.1 mmHg/ml (95% CI -2.1 to -0.18). Lactate infusion also increased cardiac efficiency, SvO2, arterial pH, and arterial glucose concentration significantly. The infusion of lactate led to no changes in systemic arterial pressure nor pulmonary pressures including pulmonary artery wedge pressure. Also, no changes were found in left ventricle end systolic elastance (contractility). Futhermore, no change in left ventricle end-diastolic volume or -pressure (preload) were observed during lactate infusion compared with the control (figure 2). Conclusion High dose lactate infusion increased cardiac output by reducing afterload. No changes in left ventricular contractility or -preload were observed.Fig 1:Lactate concentration and COFig 2:Changes of endpoint parameters

Determination of Left Ventricular Preload and Contractility Using Waveform Analysis in Continuous-Flow Left Ventricular Assist Device Patients

<h3>Purpose</h3> In left ventricular assist device (LVAD) patients, optimization of ventricular unloading and myocardial contractility are known to improve heart failure-related events and exercise tolerance. Left ventricular (LV) preload (dQ/dt_diastolic) and LV contractility (RI_Q; the ratio between maximum flow acceleration, dQ/dt_max, and flow pulsatility, Q_P2P) can be determined from analysis of LVAD flow waveforms. With destination therapy indication, longitudinal changes in patient hemodynamic and myocardial function, and predictors of these parameters, is clinically relevant. This study characterized longitudinal changes in LV preload and LV contractility using non-invasive waveform analysis. <h3>Methods</h3> A prospective, observational study of 17 patients (mean age 53.3 years; 82% male) implanted with a HeartWare HVAD was performed in an outpatient clinic. Over 7 months, 94 flow waveforms were captured and digitized using a smartphone application, WaveApp. RI_Q and dQ/dt_diastolic were calculated for each waveform using MATLAB scripts. Linear mixed model analysis was performed. <h3>Results</h3> There was an increase in LV preload with longer duration of LVAD support (0.26±0.099 mmHg per 100 days; p=0.014). There was no effect of pump speed and diuretic use, however, higher mean pressure (MAP), poorer kidney function and older age at implant were positively associated with preload. Higher LV preload was linked with poorer LV contractility (0.064±0.021 s^-1 per mmHg; p=0.003). There was no significant change in LV contractility with duration of pump support. <h3>Conclusion</h3> Using flow waveform analysis, an increase in LV preload is associated with longer duration of pump support. We propose higher MAP driving increased afterload as the mechanism for reduced pump efficiency and observed increase in preload. Lower LV preload was associated with improved LV contractility, supporting the optimization of ventricular unloading to improve reverse remodeling.

Effector mechanisms in the baroreceptor control of blood pressure.

While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular contractility on end-systolic volume may have been less understood and appreciated and the effects of changes in venous capacitance on end-diastolic volume may have been unknown to many readers. Herein, we have provided a brief review for the medical student and beginning graduate student highlighting these sometimes-complex relationships.

Early changes in left ventricular myocardial function by 2D speckle tracking layer-specific technique in neonates with hyperbilirubinemia.

Hyperbilirubinemia (HBN) can cause myocardial injury in neonates. Advancement in myocardial deformation imaging allows the detection of subclinical changes in myocardial contractility. The present study aimed to evaluate the changes in left ventricular contractility in newborns with hyperbilirubinemia by 2D speckle tracking imaging (STI). A group of 134 neonates who reached the diagnostic level of HBN as the HBN group was selected. The control group included 56 healthy newborns. The interventricular septum, anterior partition, anterior wall, sidewall, posterior wall, and inferior wall were separated into the basal, middle, and apical segments. In each segment, speckle tracking analysis was performed in the subintimal, middle, and subadventitial myocardium. The overall longitudinal strain of the myocardium in different ventricular walls and segments and global longitudinal strain (GLS) were computed. At the same time, the laboratory results of blood gas analysis, blood routine tests, liver function, and myocardial enzyme spectrum in HBN neonates were collected and correlated with the left ventricular stratified strain parameters. The gradient of the left ventricular GLS had the same characteristics in both groups of newborns. There was a decreasing trend of longitudinal strain (LS) from the intima to the adventitia (i.e., GLSendo > GLSmid > GLSepi). This gradient was also present in stratified LS in each myocardial segment (P<0.001). The LS showed an increasing trend from the basal to the apical segment (P<0.001). The LS of the ventricular septum, anterior wall (or anterior septum), inferior wall, lateral wall, and posterior wall showed a decreasing trend (P<0.001). Stratified strain parameters of the ventricular wall (i.e., the 3-layer myocardium: LSendo-SEPT, LSmid-SEPT, and LSepi-SEPT) were all significantly lower in the HBN group than in the control group (P=0.019, P=0.019, and P=0.023, respectively). LSedo-ANT, LSmid-ANT, and LSepi-ANT were also reduced, and the difference between LSendo-ANT and LSepi-ANT was statistically significant. The segmental stratified strain parameters (i.e., the apical 3-layer myocardium: LSepi-a, LSmid-a, and LSepi-a) decreased, and the difference in LSepi-a was statistically significant (P=0.043). Overall strain parameters (i.e., the 3-layer myocardial overall strain: GLSendo, GLSmid, and GLSepi) were reduced, but the difference was not statistically significant (P=0.612, P=0.653, and P=0.585, respectively). The subclinical changes in systolic function in the HBN group, reflected by the parameters of longitudinal myocardial strain, correlate to some extent with multiple results of laboratory tests. 2DSTI stratified strain technology can quantitively evaluate changes in the LS of the left ventricle in different ventricular walls, wall segments, and layers of the myocardium.

Relationship Between Left Ventricular Ejection Fraction Variation and Systemic Vascular Resistance: A Prospective Cardiovascular Magnetic Resonance Study.

Introduction: This cardiovascular magnetic resonance (CMR) study aims to determine whether changes in systemic vascular resistance (SVR), obtained from CMR flow sequences, might explain the significant long-term changes in left ventricular (LV) ejection fraction (EF) observed in subjects with no cardiac disease history.Methods: Cohort subjects without any known cardiac disease but with high rates of hypertension and obesity, underwent CMR with phase-contrast sequences both at baseline and at a median follow-up of 5.2 years. Longitudinal changes in EF were analyzed for any concomitant changes in blood pressure and vascular function, notably the indexed SVR given by the formula: mean brachial blood pressure / cardiac output x body surface area.Results: A total of 118 subjects (53 ± 12 years, 52% women) were included, 26% had hypertension, and 52% were obese. Eighteen (15%) had significant EF variations between baseline and follow-up (7 increased EF and 11 decreased EF). Longitudinal changes in EF were inversely related to concomitant changes in mean and diastolic blood pressures (p = 0.030 and p = 0.027, respectively) and much more significantly to SVR (p < 0.001). On average, these SVR changes were −8.08 ± 9.21 and +8.14 ± 8.28 mmHg.min.m2.L−1, respectively, in subjects with significant increases and decreases in EF, and 3.32 ± 7.53 mmHg.min.m2.L−1 in subjects with a stable EF (overall p < 0.001).Conclusions: Significant EF variations are not uncommon during the long-term CMR follow-up of populations with no evident health issues except for uncomplicated hypertension and obesity. However, most of these variations are linked to SVR changes and may therefore be unrelated to any intrinsic change in LV contractility. This underscores the benefits of specifically assessing LV afterload when EF is monitored in populations at risk of vascular dysfunction.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01716819 and NCT02430805.

Transmural Distribution of Coronary Perfusion and Myocardial Work Density Due to Alterations in Ventricular Loading, Geometry and Contractility.

Myocardial supply changes to accommodate the variation of myocardial demand across the heart wall to maintain normal cardiac function. A computational framework that couples the systemic circulation of a left ventricular (LV) finite element model and coronary perfusion in a closed loop is developed to investigate the transmural distribution of the myocardial demand (work density) and supply (perfusion) ratio. Calibrated and validated against measurements of LV mechanics and coronary perfusion, the model is applied to investigate changes in the transmural distribution of passive coronary perfusion, myocardial work density, and their ratio in response to changes in LV contractility, preload, afterload, wall thickness, and cavity volume. The model predicts the following: (1) Total passive coronary flow varies from a minimum value at the endocardium to a maximum value at the epicardium transmurally that is consistent with the transmural distribution of IMP; (2) Total passive coronary flow at different transmural locations is increased with an increase in either contractility, afterload, or preload of the LV, whereas is reduced with an increase in wall thickness or cavity volume; (3) Myocardial work density at different transmural locations is increased transmurally with an increase in either contractility, afterload, preload or cavity volume of the LV, but is reduced with an increase in wall thickness; (4) Myocardial work density-perfusion mismatch ratio at different transmural locations is increased with an increase in contractility, preload, wall thickness or cavity volume of the LV, and the ratio is higher at the endocardium than the epicardium. These results suggest that an increase in either contractility, preload, wall thickness, or cavity volume of the LV can increase the vulnerability of the subendocardial region to ischemia.

Abstract 13856: Hydrogen Sulfide Donor, SG1002, Preserves Left Ventricular Global Function and Contractile Reserve in a Mouse Model of Doxorubicin Cardiotoxicity

Background: Despite being one of the most widely used chemotherapeutic agents, Doxorubicin [DOX] is limited by its dose-dependent side effects, including cardiotoxicity and heart failure (HF). Reactive oxygen species, inflammation, mitochondrial dysfunction, and dysregulated autophagy have been proposed as potential mediators of cardiotoxicity. Hydrogen sulfide (H 2 S) has been shown to promote mitochondrial stability and reduce inflammation in the setting of myocardial infarction. Hypothesis: To determine if the orally active, slow-releasing H 2 S-compound SG1002 attenuates DOX-induced cardiotoxicity. Methods: Following baseline echocardiography, male C57BL mice (12 weeks old) were treated with DOX (5 doses of 5mg/kg, ip; once a week) over 5 weeks. One week before the first DOX treatment, mice were placed onSG1002-enriched chow to achieve a dosage of 40 mg/kg/day for the duration of the study. The control group received normal chow. Mice were followed up to 5 weeks after the last DOX treatment. Left ventricular (LV) function was assessed via echocardiography, including LV global longitudinal strain [GLS]. Contractile reserve was measured as a percent increase in LV ejection fraction (LVEF) following isoproterenol challenge (10ng/mouse). Results: The cumulative dose of 25mg/kg of DOX led to impaired cardiac contractile reserve in control mice, which was preserved in SG1002-fed mice (Fig.A). Despite no changes observed in LVEF throughout the study, LV GLS detected early signs of cardiac dyssynchrony following the DOX regimen (Fig.B). SG1002 treatment prevented the early decline in cardiac function following chemotherapy. Conclusion: Our results indicate that LV GLS and cardiac contractile reserve are able to detect early changes in LV contractility due to cardiotoxicity following DOX treatment, which can be prevented with SG1002. This further highlights the importance of early screening with advanced imaging to identify signs of cardiotoxicity.

Impact of drug-eluting stents on left ventricular wall motion after successful reperfusion of first anterior ST elevation myocardial infarction.

BACKGROUND Timely myocardial reperfusion by primary percutaneous coronary intervention (pPCI) prevents the development of left ventricular (LV) dysfunction after myocardial infarction (MI). We aimed to investigate whether bare-metal stents (BMS) and drug eluting stents (DES) differently affect the recovery of LV function in patients with ST-elevation MI (STEMI). METHODS Overall 103anterior STEMI patients were retrospectively analyzed. All patients had single vessel disease with culprit lesion at the left anterior descending coronary artery. Patients were categorized in DES group (N.=67) and BMS group (N.=36). Changes in LV contractility were assessed by trans-thoracic echocardiogram as Left Ventricular Wall Motion Score Index (LVWMSI). Follow-up visits were performed between 6 and 12 months after hospital discharge. RESULTS Compared to baseline, LV ejection fraction (EF) remained unchanged between the two groups at the follow-up; LVWMSI significantly improved in patients treated with DES (1.95±0.25 vs. 1.78±0.38, P<0.05), whereas did not change in those treated with BMS (2.09±0.21 vs. 1.98±0.33, P: not significant). At follow-up the LVWMSI was significantly higher in patients with DES than with BMS (P=0.048). LV end-systolic and end-diastolic volumes (LVESV, LVEDV) significantly increased in patients receiving a BMS, whereas it did not change in those receiving a DES (P<0.05). Multivariate analysis adjusted for age, gender, type of stent (DES or BMS), and type of revascularization (primary PCI or rescue PCI or thrombolysis + PCI) showed that DES implantation was an independent predictor of LVWMSI improvement (OR: 3.8 [1.143-12.969] P=0.03). CONCLUSIONS DES implantation is associated with a favorable impact on LV remodeling and regional contractility.

Impact of drug-eluting stents on left ventricular wall motion after successful reperfusion of first anterior ST elevation myocardial infarction.

Timely myocardial reperfusion by primary percutaneous coronary intervention (pPCI) prevents the development of left ventricular (LV) dysfunction after myocardial infarction (MI). We aimed to investigate whether bare-metal stents (BMS) and drug eluting stents (DES) differently affect the recovery of LV function in patients with ST-elevation MI (STEMI). Overall 103anterior STEMI patients were retrospectively analyzed. All patients had single vessel disease with culprit lesion at the left anterior descending coronary artery. Patients were categorized in DES group (N.=67) and BMS group (N.=36). Changes in LV contractility were assessed by trans-thoracic echocardiogram as Left Ventricular Wall Motion Score Index (LVWMSI). Follow-up visits were performed between 6 and 12 months after hospital discharge. Compared to baseline, LV ejection fraction (EF) remained unchanged between the two groups at the follow-up; LVWMSI significantly improved in patients treated with DES (1.95±0.25 vs. 1.78±0.38, P<0.05), whereas did not change in those treated with BMS (2.09±0.21 vs. 1.98±0.33, P: not significant). At follow-up the LVWMSI was significantly higher in patients with DES than with BMS (P=0.048). LV end-systolic and end-diastolic volumes (LVESV, LVEDV) significantly increased in patients receiving a BMS, whereas it did not change in those receiving a DES (P<0.05). Multivariate analysis adjusted for age, gender, type of stent (DES or BMS), and type of revascularization (primary PCI or rescue PCI or thrombolysis + PCI) showed that DES implantation was an independent predictor of LVWMSI improvement (OR: 3.8 [1.143-12.969] P=0.03). DES implantation is associated with a favorable impact on LV remodeling and regional contractility.

Continuous Hemodynamic Monitoring in an Intact Rat Model of Simulated Diving.

Cardiovascular risk is elevated in divers, but detailed information of cardiac function during diving is missing. The aim of this study was to apply an intact rat model with continuous monitoring of cardiac left ventricular (LV) function in a simulated diving experiment. Thirteen rats were inserted with a LV pressure–volume catheter and a pressure transducer in the femoral artery to measure hemodynamic variables, and randomly assigned to diving (n = 9) and control (n = 4) groups. The diving group was compressed to 600 kPa in air, maintained at pressure for 45 min (bottom phase), and decompressed to surface at 50 kPa/min. Data was collected before, during, and up to 60 min after exposure in the diving group, and at similar times in non-diving controls. During the bottom phase, stroke volume (SV) (−29%) and cardiac output (−30%) decreased, whereas LV end-systolic volume (+13%), mean arterial pressure (MAP) (+29%), and total peripheral resistance (TPR) (+72%) increased. There were no changes in LV contractility, stroke work, or diastolic function. All hemodynamic variables returned to baseline values within 60 min after diving. In conclusion, our simulated dive experiment to 600 kPa increased MAP and TPR to levels which caused a substantial reduction in SV and LV volume output. The increase in cardiac afterload demonstrated to take place during a dive is well tolerated by the healthy heart in our model, whereas in a failing heart this abrupt change in afterload may lead to acute cardiac decompensation.

Excellent Restoration of Left Ventricular Compliance After Prolonged Del Nido Single-Dose Cardioplegia in an In Vivo Piglet Model

Del Nido cardioplegia (DN) is used in congenital heart surgery and recently in adults, a single dose has been administered. However, the tolerable ischemic time has not been established. The objective is to evaluate the left ventricular (LV) function recovery and accompanying biochemical and histologic markers to clarify the tolerable ischemic time in an in vivo cardiopulmonary bypass (CPB) piglet model. Twenty-one piglets were subjected to either 90 minutes (with or without topical cooling; TC) or 120 minutes (with TC) of global ischemia induced by single-dose DN, while the other 7 served as the control group (CPB only). The CPB temperature was established with a perfusion temperature of 30°C. The LV function recovery was assessed by the percent change in end-systolic elastance (Ees) and the end-diastolic pressure-volume relationship (EDPVR). Creatine kinase-MB (CK-MB) levels and the mitochondrial score were also assessed. LV contractility assessed by %Ees after 90 and 120 minutes of ischemia (89.3 ± 20.6% and 57.9 ± 17.8%) was lower compared with the control group (122.6 ± 35.8%, P = 0.001). Conversely, LV compliance assessed by %EDPVR was preserved in both groups (102.7 ± 28.2% and 88.5 ± 24.0%), which was comparable to the control group (105.8 ± 36.9%, P = 0.531). There was no change in LV contractility after 90 minutes of ischemia with or without TC (89.3 ± 20.6% or 84.8 ± 16.2%, P = 0.657), whereas LV compliance was lower but not statistically different without TC (102.7 ± 28.2% vs 78.0 ± 38.9%). CK-MB and the mitochondrial score were equivalent between all groups. The proposed single-dose ischemic time for redosing is 90 minutes using TC.

Performance comparison of ventricular and arterial dP/dtmax for assessing left ventricular systolic function during different experimental loading and contractile conditions

BackgroundMaximal left ventricular (LV) pressure rise (LV dP/dtmax), a classical marker of LV systolic function, requires LV catheterization, thus surrogate arterial pressure waveform measures have been proposed. We compared LV and arterial (femoral and radial) dP/dtmax to the slope of the LV end-systolic pressure-volume relationship (Ees), a load-independent measure of LV contractility, to determine the interactions between dP/dtmax and Ees as loading and LV contractility varied.MethodsWe measured LV pressure-volume data using a conductance catheter and femoral and radial arterial pressures using a fluid-filled catheter in 10 anesthetized pigs. Ees was calculated as the slope of the end-systolic pressure-volume relationship during a transient inferior vena cava occlusion. Afterload was assessed by the effective arterial elastance. The experimental protocol consisted of sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid bolus), and contractility (esmolol/dobutamine). A linear-mixed analysis was used to assess the contribution of cardiac (Ees, end-diastolic volume, effective arterial elastance, heart rate, preload-dependency) and arterial factors (total vascular resistance and arterial compliance) to LV and arterial dP/dtmax.ResultsBoth LV and arterial dP/dtmax allowed the tracking of Ees changes, especially during afterload and contractility changes, although arterial dP/dtmax was lower compared to LV dP/dtmax (bias 732 ± 539 mmHg⋅s− 1 for femoral dP/dtmax, and 625 ± 501 mmHg⋅s− 1 for radial dP/dtmax). Changes in cardiac contractility (Ees) were the main determinant of LV and arterial dP/dtmax changes.ConclusionAlthough arterial dP/dtmax is a complex function of central and peripheral arterial factors, radial and particularly femoral dP/dtmax allowed reasonably good tracking of LV contractility changes as loading and inotropic conditions varied.

Organ-level validation of a cross-bridge cycling descriptor in a left ventricular finite element model: effects of ventricular loading on myocardial strains.

Although detailed cell‐based descriptors of cross‐bridge cycling have been applied in finite element (FE) heart models to describe ventricular mechanics, these multiscale models have never been tested rigorously to determine if these descriptors, when scaled up to the organ‐level, are able to reproduce well‐established organ‐level physiological behaviors. To address this void, we here validate a left ventricular (LV) FE model that is driven by a cell‐based cross‐bridge cycling descriptor against key organ‐level heart physiology. The LV FE model was coupled to a closed‐loop lumped parameter circulatory model to simulate different ventricular loading conditions (preload and afterload) and contractilities. We show that our model is able to reproduce a linear end‐systolic pressure volume relationship, a curvilinear end‐diastolic pressure volume relationship and a linear relationship between myocardial oxygen consumption and pressure–volume area. We also show that the validated model can predict realistic LV strain‐time profiles in the longitudinal, circumferential, and radial directions. The predicted strain‐time profiles display key features that are consistent with those measured in humans, such as having similar peak strains, time‐to‐peak‐strain, and a rapid change in strain during atrial contraction at late‐diastole. Our model shows that the myocardial strains are sensitive to not only LV contractility, but also to the LV loading conditions, especially to a change in afterload. This result suggests that caution must be exercised when associating changes in myocardial strain with changes in LV contractility. The methodically validated multiscale model will be used in future studies to understand human heart diseases.

Echocardiographic Prediction of Cardiac Resynchronization Therapy Response Requires Analysis of Both Mechanical Dyssynchrony and Right Ventricular Function: A Combined Analysis of Patient Data and Computer Simulations

Pronounced echocardiographically measured mechanical dyssynchrony is a positive predictor of response to cardiac resynchronization therapy (CRT), whereas right ventricular (RV) dysfunction is a negative predictor. The aim of this study was to investigate how RV dysfunction influences the association between mechanical dyssynchrony and left ventricular (LV) volumetric remodeling following CRT. One hundred twenty-two CRT candidates (mean LV ejection fraction, 19±6%; mean QRS width, 168±21msec) were prospectively enrolled and underwent echocardiography before and 6months after CRT. Volumetric remodeling was defined as percentage reduction in LV end-systolic volume. RV dysfunction was defined as RV fractional area change<35%. Mechanical dyssynchrony was assessed as time to peak strain between the septum and LV lateral wall, interventricular mechanical delay, and septal systolic rebound stretch. Simulations of heart failure with an LV conduction delay in the CircAdapt computer model were used to investigate how LV and RV myocardial contractility influence LV dyssynchrony and acute CRT response. In the entire patient cohort, higher baseline septal systolic rebound stretch, time to peak strain between the septum and LV lateral wall, and interventricular mechanical delay were all associated with LV volumetric remodeling in univariate analysis (R=0.599, R=0.421, and R=0.410, respectively, P<.01 for all). The association between septal systolic rebound stretch and LV volumetric remodeling was even stronger in patients without RV dysfunction (R=0.648, P<.01). However, none of the mechanical dyssynchrony parameters were associated with LV remodeling in the RV dysfunction subgroup. The computer simulations showed that low RV contractility reduced CRT response but hardly affected mechanical dyssynchrony. In contrast, LV contractility changes had congruent effects on mechanical dyssynchrony and CRT response. Mechanical dyssynchrony parameters do not reflect the negative impact of reduced RV contractility on CRT response. Echocardiographic prediction of CRT response should therefore include parameters of mechanical dyssynchrony and RV function.

Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p < 0.001) circumferential (p = 0.02) and radial (p < 0.01)strain compared to controls, despite ejection fraction was similar for both groups [(p = 0.45) for three dimensional and (p = 0.37) for two dimensional measurement]. While the twist angle was not significantly different between groups (p = 0.11), left ventricular torsion was significantly higher in mitral stenosis group (p = 0.03). All strain values had a weak but significant positive correlation with mitral valve area measured with planimetry. Subclinical left ventricular systolic dysfunction develops at an early stage in rheumatic mitral stenosis. Further work is needed to elucidate patients at risk for developing overt systolic dysfunction.

Cellular basis of angiotensin-(1-7)-induced augmentation of left ventricular functional performance in heart failure

BackgroundAngiotensin-(1-7) [Ang-(1-7)] exhibits cardiovascular effects opposite those of angiotensin II (Ang II), thus providing protection against heart disease. However, how Ang-(1-7) imparts cardioprotection is unclear, and its direct cardiac effects are controversial. Whether heart failure (HF) alters cardiac contractile responses to Ang-(1-7) remains undetermined. We tested the hypothesis that in HF, Ang-(1-7) may produce positive modulation on [Ca2+]i regulation, enhancing left ventricular (LV) and myocyte contraction and relaxation via Ang-(1-7) Mas receptor coupled with nitric oxide (NO)/bradykinin (BK)-mediated mechanism. Methods and resultsWe measured LV contractility changes after Ang-(1-7) (650ng/kg, iv) and compared myocyte functional and [Ca2+]i transient ([Ca2+]iT) responses to Ang-(1-7) superfusion in 24 normal rats and 34 rats with isoproterenol-induced HF (3months after 170mg/kg, s.q. for 2days). To assess the mechanisms of altered HF responses to Ang-(1-7), subsets of HF myocytes were pretreated to inhibit NO synthase (L-NAME), BK (HOE-140), and Mas receptor (A-779) followed with Ang-(1-7). In normal rats, Ang-(1-7) produced no significant changes in LV and myocyte function. In HF rats, Ang-(1-7) significantly augmented LV contractility and relaxation with increased EES (51%), but decreased τ compared to baseline. Ang-(1-7) also significantly increased myocyte contraction (dL/dtmax, 30%), relaxation (dR/dtmax, 41%), and [Ca2+]iT. L-NAME increased, HOE-140 decreased, and A-779 prevented HF myocyte contractile responses to Ang-(1-7). ConclusionsIn a rat model of HF, Ang-(1-7) increases [Ca2+]iT, and produces positive inotropic and lusitropic effects in the LV and myocytes. These effects are mediated by the Mas receptor and involve activation of NO/BK pathways.

Abstract 19128: Acute Changes in Left Ventricular Contractility Following Mitraclip Implantation Depend on Left Atrial Volume

Background: The acute hemodynamic changes following elimination of mitral regurgitation is a much discussed issue, particularly in patients with severely compromised left ventricular function where the incompetent mitral valve was regarded as a pop-off valve. Herein, we investigated the acute changes of ventricular contractility in relation to left atrial volume. Methods and results: Echocardiographic left atrial and left ventricular longitudinal strain measurements before and 3 days after the procedure were performed in 19 patients (mean age: 77.9±7.9, 47% female, 73,7% functional mitral valve regurgitation, 26,3% degenerative mitral valve regurgitation) undergoing MitraClip implantation at our institution. Procedural success with reduction in MR to grade 2+ or less was achieved in all patients. Overall there was no significant change in left atrial or ventricular global or regional longitudinal strain after the procedure. However, a strong correlation was observed between worsening in left ventricular strain and left atrial volume (r: -0.72, p&lt;0.01), i.e. there was a greater reduction in left ventricular contractility after clip implantation in patients with larger left atrial volumes. Multivariate, linear regression analyses revealed that left atrial volume predicted the change of left ventricular longitudinal strain following MitraClip implantation (r2: -0.07, p&lt;0.01) independently of left ventricular ejection fraction (r2: -0.05, p=0.40), mitral regurgitant volume (r2: -0.09, p=0.09) and left atrial strain (r2: -0.03, p=0.85). Discussion: Our data suggest that enlarged left atria act as a low-resistance reservoir in mitral regurgitation. As a consequence elimination of mitral regurgitation in these patients leads to worsening of left ventricular contractility whereas in smaller atria left ventricular contractility is not negatively affected by elimination of MR.

Gender differences in myocardial function and arterio-ventricular coupling in response to maximal exercise in adolescent floor-ball players.

BackgroundThe hemodynamic and cardiac responses to exercise have been widely investigated in adults. However, little is known regarding myocardial performance in response to a short bout of maximal exercise in adolescents. We therefore sought to study alterations in myocardial function and investigate sex-influences in young athletes after maximal cardiopulmonary testing.Methods51 adolescent (13-19 years old) floor-ball players (24 females) were recruited. All subjects underwent a maximal exercise test to determine maximal oxygen uptake (VO2max) and cardiac output. Cardiac performance was investigated using conventional and tissue velocity imaging, as well as 2D strain echocardiography before and 30 minutes following exercise. Arterio-ventricular coupling was evaluated by means of single beat ventricular elastance and arterial elastance.ResultsCompared to baseline the early diastolic myocardial velocity (E′LV) at the basal left ventricular (LV) segments declined significantly (females: E′LV: 14.7 +/- 2.6 to 13.6 +/- 2.9 cm/s; males: 15.2 +/- 2.2 to 13.9 +/- 2.3 cm/s, p < 0.001 for both). Similarly, 2D strain decreased significantly following exercise (2D strain LV: from 21.5 +/- 2.4 to 20.2 +/- 2.7% in females, and from 20 +/- 1 to 17.9 +/- 1.5% in males, p < 0.05 for both). However, there were no significant changes in LV contractility estimated by elastance in either sex following exercise (p > 0.05). Arterial elastance) Ea) at baseline was identified as the only predictor of VO2max in males (r = 0.76, p < 0.001) but not in females (p > 0.05).ConclusionsThe present study demonstrates that vigorous exercise of short duration results in a significant decrease of longitudinal myocardial motion in both sexes. However, in view of unaltered end systolic LV elastance (Ees), these reductions most probably reflect changes in the loading conditions and not an attenuation of myocardial function per se. Importantly, we show that arterial load at rest acts as a strong predictor of VO2max in males but not in female subjects.

Consistent Regional Heterogeneity of Passive Diastolic Stretch and Systolic Deformation in the Healthy Heart: Age-Related Changes in Left Ventricle Contractility

The consistency of the normal spatial distribution of segmental passive stretch (PreS) and systolic strain (SS) within the left ventricle was investigated and a recently proposed echocardiographic estimate of left ventricular (LV) contractility was used to detect contractility changes with age. Hereto, in 54 healthy subjects, segmental PreS and SS were measured on tissue Doppler images of six left ventricle walls. For each subject, a linear regression line was estimated through the segmental PreS and SS values. The slopes and intercepts of this PreS-SS relationship did not differ between age groups, suggesting no changes in LV contractility with age. Moreover, a consistent regional distribution of PreS was observed, with the highest values measured in the septum, resulting in a similar distribution of SS as a direct consequence of the Frank-Starling mechanism.