Left Ventricular Ejection Time Research Articles

Non-invasive measurement of volume–time curves in patients with mitral regurgitation and in healthy volunteers, using a new operator-independent screening tool

Left ventricular volume–time curves (VTCs) provide hemodynamic data, and may help clinical decision making. The generation of VTCs using echocardiography, however, is time-consuming and prone to inter-operator variability. In this study, we used a new non-invasive, operator-independent technique, the hemodynamic cardiac profiler (HCP), to generate VTCs. The HCP, which uses a low-intensity, patient-safe, high-frequency applied AC current, and 12 standard ECG electrodes attached on the thorax in a pre-defined pattern, was applied to five young healthy volunteers, five older healthy volunteers, and five patients with severe mitral regurgitation. From the VTCs generated by the HCP, the presence or absence of an isovolumetric contraction phase (ICP) was assessed, as well as the left ventricular ejection time (LVET), time of the pre-ejection period (tPEP), and ratio of the volumes of the early (E) and late (A) diastolic filling (EV/AV ratio), and compared to 2D transthoracic echocardiography (2D TTE) at rest. The reproducibility by two different operators showed good results (RMS = 5.2%). For intra-patient measurement RMS was 2.8%. Both LVET and the EV/AV ratio showed a strong significant correlation between HCP and 2D TTE derived parameters (p < 0.05). For tPEP, the correlation was still weak (p = 0.32). In all five patients with mitral regurgitation, the ICP was absent in the VTC from the HCP, whereas it was present in the 10 healthy volunteers, which is in accordance with pathophysiology. We conclude that the HCP seems to be a method for reproducible VTC generation, and may become a useful early screening tool for cardiac dysfunction in the future.

Fitter Women Did Not Have Attenuated Hemodynamic Responses to Psychological Stress Compared with Age-Matched Women with Lower Levels of Fitness.

According to the ‘cross stressor adaptation hypothesis’, regular exercise acts as a buffer against the detrimental effects of stress. Nevertheless, evidence that higher levels of cardiorespiratory fitness moderate hemodynamic responses to acute psychological stress is inconclusive, especially in women. Women aged 30–50 years (in the mid-follicular phase of the menstrual cycle) with higher (n = 17) and lower (n = 17) levels of fitness were subjected to a Trier Social Stress Test (TSST). Continuous, non-invasive measurements were made of beat-to-beat, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), left ventricular ejection time (LVET), maximum slope, pulse interval (PI) and total peripheral resistance (TPR). Maximal oxygen consumption was significantly (p<0.001) higher in the ‘higher fit’ women. Lower fit women had higher fasting glucose, resting heart rate, waist to hip ratios and elevated serum triglyceride and cholesterol/ HDL ratios compared with higher fit women (p<0.05 for all). While all measured parameters (for both groups)displayed significant (p<0.001) responses to the TSST, only HR, PI and LVET differed significantly between higher and lower fit women (p<0.001 for all) with the higher fit women having the larger response in each case. It was also found that higher fit women had significantly shorter time to recovery for maximum slope compared with the lower fit women. These findings provide little support for the notion that higher levels of cardiorespiratory fitness result in lower cardiovascular responsivity to psychological stress in women but may indicate that lower fit women have blunted responses to stress.

Abstract 13226: Shorter Left Ventricular Ejection Time is Associated With Adverse Outcomes in Heart Failure Patients With Reduced Ejection Fraction

Introduction: Worsening heart failure (HF) is thought to be associated with shorter left ventricular ejection time (LVET), but there are limited data describing the relationship between LVET and outcomes. We report the largest study to date describing the association between LVET and outcomes in an ambulatory HF population. Methods: We identified HF patients without significant structural or congenital heart disease who had an outpatient transthoracic echocardiogram (TTE) performed between 8/2008-7/2010 at Duke University Medical Center. We excluded patients with paced or irregular rhythms. All TTE were re-analyzed in triplicate. Multivariable logistic regression was used to evaluate the association between LVET and 1 year outcomes among HF patients with reduced ejection fraction (HFrEF) and patients with preserved ejection fraction (HFpEF). Results: We identified 545 HF patients (171 HFrEF, 374 HFpEF) meeting inclusion criteria. HFrEF patients were younger (median age was 60 (Quartile 1 to Quartile (Q1-Q3) 50-69) vs. 64 (Q1-Q3 53-74), with smaller proportion of females (30.4 vs. 56.4%) and similar ratio of African Americans (35.7 vs. 35.0%). Median EF among patients with HFrEF was 30% (Q1-Q3 25-35%) and with HFpEF was 54% (Q1-Q3 48-58%). There were no statistical differences in medical histories or neurohormonal therapies. Median LVET was shorter (280 vs. 315ms, p&lt;0.001), median pre-ejection period was longer (114 vs. 89ms, p&lt;0.001), and median relaxation time was shorter (351 vs 411ms, p&lt;0.001) among patients with HFrEF versus HFpEF. Death or HF hospitalization occurred in 46/171 HFrEF patients and 44/374 HFpEF patients. After adjustment, longer LVET was associated with lower odds of the composite of 1 year death/1 year HF hospitalization among HFrEF patients, but not among HFpEF (Table). Conclusion: Longer LVET is independently associated with improved outcomes among HFrEF patients supporting a potential role for increasing LVET as a therapeutic target.

Comparison of the measured pre-ejection periods and left ventricular ejection times between echocardiography and impedance cardiography for optimizing cardiac resynchronization therapy

BackgroundThe pre-ejection period (PEP) and left ventricular ejection time (LVET) are easily measured by impedance cardiography (ICG). We hypothesized that the PEP/LVET measured by ICG would correlate with that measured by echocardiography, and that PEP/LVET measured by ICG would be useful for cardiac resynchronization therapy (CRT) optimization. MethodsNewly CRT implanted patients were optimized by echocardiography. The PEP/LVET was measured by echocardiography and ICG in two different settings: optimized setting and right ventricle (RV)-only pacing. ResultsThe PEP/LVET was significantly decreased in the optimized setting compared with that in RV-only pacing (0.62±0.13 vs 0.75±0.16, p<0.05). The PEP/LVET values calculated by ICG and echocardiography were positively correlated (r=0.553, p=0.003). ConclusionICG was useful for the optimization of CRT.

Systolic time intervals combined with Valsalva maneuver for the diagnosis of left ventricular dysfunction in COPD exacerbations.

BackgroundThe goal of this study was to determine the value of systolic time intervals and their change during Valsalva maneuver (VM) in the diagnosis of left ventricular dysfunction (LVD) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).MethodsWe included 166 patients admitted to the emergency department for AECOPD. Measurement of systolic time intervals included electromechanical activation time (EMAT), left ventricular ejection time (LVET), and EMAT/LVET ratio. These were performed at baseline and during the first strain phase of the VM using a computerized phonoelectrocardiographic method. The diagnosis of LVD was determined on the basis of clinical examination, echocardiography, and brain natriuretic peptide. The values of systolic time intervals were compared between patients with and without LVD; their diagnostic performance was assessed using the area under receiver operating characteristic (ROC) curve.ResultsPatients with LVD (n=95) had a significantly higher EMAT and lower LVET and EMAT/LVET ratio compared to patients without LVD (n=71); the area under ROC curve was 0.79, 0.88, and 0.90, respectively, for EMAT, LVET, and EMAT/LVET ratio. All baseline systolic time intervals changed significantly during VM in patients without LVD but they did not change in patients with LVD. The area under ROC curve increased to 0.84 and 0.93, respectively, for EMAT and EMAT/LVET ratio but did not change for LVET.ConclusionSimple and noninvasive measurements of systolic time intervals combined with VM could be helpful to detect or rule out LVD in patients admitted to the emergency room for COPD excacerbation. The EMAT/LVET ratio seems to have the best diagnostic value.

Hemodynamic Correlates of Blood Pressure in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

The primary aim of the present study was to identify the hemodynamic correlates of both steady and pulsatile blood pressure (BP) in community-dwelling older adults. In 3762 adults aged 70 to 89 years, significant hemodynamic determinants of both brachial and carotid systolic BP included arterial stiffness as measured by aortic pulse wave velocity, stroke volume (via echocardiography), arterial wave reflection, left ventricular ejection time, and upstroke time. The strongest influence was exerted by arterial stiffness. The steady-state component of blood pressure, mean arterial pressure, was associated with both cardiac index and total peripheral resistance (TPR), but was more strongly associated with TPR. Results were similar when participants taking antihypertensive medications were excluded from analyses. The overall findings suggest that mean arterial pressure is associated strongly with TPR and that significant hemodynamic correlates of systolic BP included arterial stiffness, stroke volume, and arterial wave reflection.

Utility of Baroreflex Sensitivity as a Marker of Stress

Presently, adaptive systems use various cognitive and cardiovascular measures to evaluate the functional state of the operator. One marker that has been largely ignored as an assessment tool is baroreflex sensitivity (BRS). This study examined the extent to which BRS changed in response to acute psychological and physical stressors. A total of 20 participants underwent 6-min exposures to a psychological stressor and a physical stressor. Baroreceptor sensitivity, blood pressure, heart rate, heart rate variability, stroke volume, cardiac output, mean blood pressure, total peripheral resistance, left ventricular ejection time, and pre-ejection period were continuously measured at rest and throughout the testing period. Compared to rest, BRS significantly decreased during both the psychological and physical stressors. BRS was reduced more with the psychological stressor than the physical stressor. Heart rate and systolic blood pressure significantly increased above rest during the psychological stressor but not during the physical stressor. There were no significant differences from rest or between stressors for the other physiological markers. BRS was more robustly responsive than other cardiovascular measures commonly used to assess the psychophysiological response to stress, suggesting BRS is a useful marker for evaluating operator functional state during psychological and physical tasks.

The effectiveness of training and retraining at various frequencies on the aerobic capacity and intrinsic cardiovascular dynamics (systolic time intervals) in South African employees

Cardiovascular disease (CVD) remains a serious health threat in most countries globally, placing a severe burden on the workforce in the corporate environment. Physical activity intervention has already been indicated as an effective regime against CVD. The purpose of this study therefore, was to examine the effect of training and retraining, following different exercise programme frequencies on the aerobic capacity, and some intrinsic cardiovascular dynamics (systolic time intervals) in a cohort of male employees. In this study, 60 employees (28 and 49 years) from an academic environment were randomly assigned to 3 groups namely; experimental (A and B), and control (C) groups. Groups A and B trained 3 times/week for 12 weeks, detrained for 12 weeks and retrained (A=2 times/week and B=4 times/week) for another 12 weeks. Aerobic capacity, myocardial function (double product) and systolic time intervals were determined at baseline and at the end of each phase. Experimental groups showed significant improvement in aerobic capacity (VO 2 -peak) and myocardial function after 12 weeks of training. Furthermore, the results showed a significant increase in aerobic capacity for groups A (2 times/week) and B (4 times/week). Systolic time intervals (STIs) namely, Pre-ejection period (PEP c ), Left ventricular ejection time (LVET c ) and Intra-ventricular contraction time (IVCT) showed inconsistent responses during rest, while 30 and 120 seconds during recovery from a standardized workload, PEP c peak ratio and LVET c peak ratio showed the same tendency as the aerobic capacity. Physical intervention can improve both the aerobic function and selected cardiovascular dynamics (PEP c and LVET c ). These responses of the STIs were clearer after a standardized physical exercise test than at rest. Programme frequency remains an important factor, which determines the outcomes. Keywords: Training, retraining, aerobic capacity, systolic time intervals

Impaired Left and Right Ventricular Systolic and Diastolic Function in Response to Exercise in Patients with Diastolic Dysfunction.

Diastolic dysfunction (DD) is associated with exercise intolerance. To evaluate mechanisms of exercise intolerance in patients with DD, we performed bicycle stress echocardiography. Doppler measurements were performed at baseline, during exercise and recovery in 26 patients (58 ± 11 years) with DD and normal left ventricular ejection fraction and 6 normal controls (53 ± 5 years). Compared to controls, patients achieved similar target heart rates but lower METs (5.5 ± 2 vs. 9.8 ± 3, P < 0.01) and a higher peak pulmonary artery pressure (PAP) at peak exercise (50 ± 13 vs. 32 ± 7 mmHg, P < 0.01) despite similar PAP at rest and similar mean blood pressure at peak exercise (110.4 ± 18.0 vs. 106.9 ± 11.4 mmHg, P = NS). In patients versus controls, mitral E/E' was similar at baseline (10 ± 3 vs. 8 ± 1.3, P = NS) but higher at recovery (11 ± 2 vs. 7 ± 2, P < 0.05), % mitral filling time was shorter at baseline, onset, and peak exercise, whereas % LV and RV ejection time was similar to controls throughout exercise. Compared to controls, lateral mitral annular S' (11.8 ± 2.5 cm/sec vs. 14.9 ± 1.9 cm/sec, P < 0.02) and tricuspid annular S' (14.8 ± 4.1 cm/sec vs. 19.4 ± 4.0 cm/sec, P < 0.05) were lower at peak exercise in patients. Diastolic filling time is reduced at rest and stress while LV ejection time increases normally during exercise in DD. There is a reduced systolic reserve in LV and RV during exercise in DD. These mechanisms contribute to exercise intolerance and elevation of left atrial and PAP in patients with DD.

Pulse wave analysis by digital photoplethysmography to record maternal hemodynamic effects of spinal anesthesia, delivery of the baby, and intravenous oxytocin during cesarean section

Objective: To investigate changes in maternal ECG ST index, blood pressure (BP), cardiac left ventricular (LV) ejection function and vascular tone/stiffness in large and small arteries occurring during elective cesarean section (CS) in spinal anesthesia.Material and methods: Twenty-six women were monitored with photoplethysmographic digital pulse wave (PW) analysis (DPA) before and after spinal anesthesia, after delivery of the baby, after 5 IU oxytocin bolus IV, and 5 min later. Statistics with Wilcoxon matched-pairs signed-rank and Friedman tests at a p < 0.05 were performed.Results: Spinal anesthesia resulted in significantly decreased BP, increased ST index and LV ejection time, and small-artery vasodilation. Delivery of the baby resulted in global vasoconstriction and increases in systolic BP and heart rate (HR). Oxytocin lowered BP, HR and ST index, increased LV ejection power and caused both large- and small-artery vasodilation. ST index and BP recovered after 5 min, but low HR and low vascular tone persisted.Conclusions: Spinal anesthesia and oxytocin caused arterial vasodilation and cardiac affection. Oxytocin caused a decrease in HR despite a fall in BP, indicating a direct negative chronotropic effect. Delivery of the baby caused momentous cardiovascular changes, possibly due to maternal emotions and auto-transfusion of blood from the uterus.

Effect of Age on Left Ventricular Global Dyssynchrony in Asymptomatic Individuals: A Population Study.

Left ventricular (LV) segmental dyssynchrony is common in patients with heart failure or myocardial activation abnormalities and is associated with increased cardiovascular risk. Total isovolumic time (t-IVT) and Tei index are sensitive indexes of global ventricular dyssynchrony. The aim of this study was to investigate the effect of age on t-IVT and Tei index. We evaluated 410 individuals with no evidence for coronary heart disease or activation abnormalities. T-IVT was calculated as 60 - (total ejection time + total filling time) and Tei index as t-IVT/total ejection time. The relationship between age, LV systolic and diastolic function parameters as well as t-IVT and Tei index was studied. Ejection fraction and stroke volume did not change with age, whereas early diastolic filling velocity fell and atrial systolic velocity increased, reducing the E/A ratio. Isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) lengthened. With every 10 years of age, total LV ejection time shortened by 1.5 sec/min and total filling time by 2.1 sec/min. T-IVT and Tei index increased with age and strongly correlated with IVCT and E/A, but not with ejection fraction or QRS duration. Normal aging is associated with worsening of LV global dyssynchrony shown by prolongation of isovolumic times resulting in shortening of filling and ejection times. Age also affects diastolic function as shown by E/A but not systolic function parameters, ejection fraction or stroke volume. Worsening of global dyssynchrony correlates with that of diastolic function but not with QRS duration.

Abstract P161: Effect of Yoga Program on Cardiovascular Function in Elderly with Stage-I Hypertension

Introduction: Hypertension is a major cause of cardiovascular (CV) morbidity and mortality in elderly population. Hypertension along with aging leads to left ventricular hypertrophy, systolic and diastolic dysfunction and congestive heart failure. We aimed to determine the effect of yoga program on cardiovascular indices in elderly with stage-I hypertension. Hypothesis: We hypothesize that yoga lifestyle modality may induce significant beneficial changes in cardiovascular function in elderly individuals with hypertension. Yoga program may be more beneficial than walking for cardiovascular health in elderly. Methods: A parallel arm, open label, single blind, randomized controlled study was conducted on elderly people with stage-I hypertension aged above 60 years (n=44). Yoga group (n=24) was assigned for yoga practice (includes asanas, pranayama and meditation) and control group (n=20) for brisk-walk for one hour in the morning for 6 days in a week for three months. The outcome measures were cardiovascular indices derived from pulse wave analysis such as left ventricular ejection time (ET), diastolic time (DT) pulse duration (PD), percentage of mean arterial pressure (%MAP), upstroke time (UT), ejection slope (ES), ejection duration index (ED%), pre-ejection period (PEP), and heart rate. Results: The mean within-yoga group change in PD(ms) was -50.29 (CI=-98.5, -2.07; p=0.042), DT(ms): -49.04 (CI=-88.47, -9.61; p=0.017), ED%: 2.107 (CI=0.92, 3.28; p=0.001), HR(bpm): 4.41 (CI=0.43, 8.4; p=0.031), %MAP: 2.08 (CI=0.71, 3.44; p=0.04), ES (mmHg/ms): 14.62 (CI=-3.99, 33.24; p=0.118), ET (ms): -0.66 (CI=11.89, 10.55; p=0.903), UT(ms): -2.54 (CI=14.95, 9.87; p=0.676), PEP (ms): -1.25 (CI=-4.17, 1.67; p=0.11). The mean within-control group change in PD(ms) was 11.15 (CI=-52.26, 74.56; p=0.717), DT(ms): 11.3 (CI=-50.56, 73.16; p=0.706), ED%: -0.101 (CI=-2.7, 2.5; p=0.936), HR (bpm): 0.35 (CI=-4.71, 5.41; p=0.887), %MAP: 0.65 (CI=-1.11, 2.41; p=0.451), ES(mmHg/ms): 0.75 (CI=-15.8, 17.38; p=0.926), ET(ms): 2.2 (CI=-10.5, 14.9; p=0.721), UT(ms): 4.7 (CI=-8.19, 17.59; p=455), PEP (ms): 2.1 (CI=-0.52, 4.72; p=0.11). Analysis of Covariance showed a significant change between-groups in PD (p=0.021), DT (p=0.02), UT (p=0.048), ED% (p=0.049), HR (p=0.036) while no significant difference was observed in ES (p=0.248), ET (p=0.245), PEP (p=0.102) and %MAP (p=0.262). Conclusions: These findings indicate that the yoga practice can induce beneficial changes in cardiovascular function in elderly hypertensive subjects. Further, yoga may be better than walking in improving cardiac health in older individuals.

Abstract P303: Early Changes in Vascular Structure and Function after Bariatric Surgery in an Appalachian Population

Obesity is associated with an elevated risk of cardiovascular disease, metabolic disease, and cardiac mortality. Reactive oxygen species and inflammation in an obese individuals are among a number of suspected driving forces behind obesity’s detrimental health effects. These factors can elevate cardiovascular risk by causing impairments in cardiovascular structure and function. It is hypothesized that gastric bypass surgery will lead to near immediate reversal of metabolic deviations and rapid weight reduction, in addition to remodeling and improvements in arterial function as weight is lost. Patients that meet protocol inclusion criteria are invited to join the study during their 1 week pre-operative clinical appointment. At this time patients are consented and instructed to lie supine for 10 minutes of quite relaxation. Patients then begin a sequence of non-invasive examinations starting with a 12-lead electrocardiogram, followed by an echocardiogram, carotid artery ultrasound, radial applanation tonometry, and endothelial function analysis using EndoPAT technology. Upon completion of the non-invasive procedures a blood sample is taken for analysis. Preliminary results on 12 study subjects suggests the following. As hypothesized, body weight had decreased (pre: 131.8 ±5.6 to post: 125 ±5.2 kg) along with BMI (pre: 45.2 ±2.3 to post: 42.9 ± 2.2) and waist circumference (pre: 122.1 ±5.0 to post: 111.9 ± 3.2 cm) at the 1-week time point. Decrease in body size and weight was aided by a reduction in low-density lipoprotein (pre: 127 ±6.2 to post: 113 ±4.5 mg/dL). In addition, a number of improvements to the cardiovascular system were also marked at the 1-week time point. Estimated left ventricular end systolic pressure and direct measure of left ventricular end systolic volume (pre: 66 ±4 to post: 55 ±3 mmHg) declined post-GBS. This is in consort with an increase in contraction rate (dP/dt pre: 672 ±54 post: 737 ±46, p&lt;0.01), a reduction in LV ejection time (pre: 291 ±10 to post: 211 ± 30ms), and a decrease in myocardial oxygen demand (PTIs pre: 2346 ±120 post: 2194 ±107 area/min, p&lt;0.05). Similar improvements in augmentation index can be seen in assessments of peripheral vessels. Independent of brachial artery blood pressure, central systolic blood pressure (pre: 112 ± 4 to post: 105 ±2 mmHg, p=0.08), augmentation index (pre: 16 ±3 to post: 8 ±3, p=0.06), an indirect measure of arterial stiffness, and central augmentation pressure (pre: 4.9 ±1.1 to post: 2.5 ±0.9 mmHg, p=0.06) tended to decrease 1-week post GBS. The data suggests that vascular changes are happening in the early stages of recovery, prior to dramatic weight loss, thus suggesting vascular changes are a result of an alternate surgical benefit. In conclusion, the preliminary results of this study suggest noteworthy cardiovascular improvements post-gastric bypass surgery, yet prior to significant weight loss.

Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure: The ATOMIC-AHF Study

BackgroundOmecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure. ObjectivesThis study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF). MethodsPatients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts. ResultsIn 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p < 0.0001) and decreases in end-systolic dimension (p < 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95). ConclusionsIn patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013)

Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure

Introduction: Current available inotropic agents increase cardiac contractility, but are associated with myocardial ischemia, arrhythmias, and mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil (CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac contractility.Areas covered: This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of omecamtiv mecarbil. Omecamtiv mecarbil represents a novel therapeutic approach to directly improve cardiac function and is therefore proposed as a potential new treatment of patients with systolic heart failure. The authors review results of previous studies investigating the effect of omecamtiv mecarbil in heart failure animal models, healthy volunteers, and patients with acute and chronic systolic heart failure.Expert opinion: Results of phase I and phase II studies demonstrate that omecamtiv mecarbil is safe and well tolerated both as an intravenous and oral formulation. In healthy volunteers and chronic systolic heart failure patients, administration of omecamtiv mecarbil resulted in a concentration-dependent increase of left ventricular ejection time, ejection fraction, fractional shortening, and stroke volume. The first results of a double-blind, randomized, placebo-controlled phase IIb dose-finding study with the oral formulation of omecamtiv mecarbil demonstrated beneficial effects on cardiac function and N-terminal pro-brain natriuretic peptide levels. This study will provide essential dosing information for the requisite phase III trials which will investigate whether the beneficial effects of omecamtiv mecarbil translate into improved clinical outcomes.

Abstract 18692: Evolution of Diastolic Parameters and Their Relationship to Heart Rate in the 7-15 Week Human Fetus

Objectives: Fetal echo offers a unique opportunity to investigate cardiac function in humans from the 1st trimester. We sought to explore the evolution left ventricular (LV) diastolic parameters and their relationship to fetal heart rate (HR) from 7-15 weeks gestational age (GA). Methods: We prospectively performed fetal echo in 137 healthy pregnancies recruited from 7+0 to 15+0 (mean 11.5±2.1) weeks GA. From Doppler studies we measured LV isovolumic relaxation time (IRT), mitral valve (MV) inflow patterns,and duration, diastolic time (IRT+inflow duration), LV ejection time (ET) and systolic time interval (isovolumic contraction time+ET). All variables were compared to GA and HR and were assessed as a proportion of the cardiac cycle length (R-R). Data were analyzed by regression and correlation analyses. Results: Results: From 7+0-15+0 weeks, HR and GA showed a non-linear relationship (R2=0.55, p&lt;0.001) with low HRs at 7-8 weeks, peaking between 8-9 weeks, then falling thereafter. Diastolic time linearly increased with GA (R2=0.65, p&lt;0.001) and inversely correlated with HR (r=0.77, p&lt;0.001). IRT showed a nonlinear inverse relationship with GA (R2= 0.70, p&lt;0.001), but did not correlate with HR, and IRT/RR increased linearly with GA (R2=0.71, p&lt;0.001). Both inflow duration and inflow duration/R-R linearly increased with GA (R2=0.81,p&lt;0.001). Inflow duration inversely correlated with HR (r=-0.70) and with IRT (r=-0.71) and IRT/R-R (r=-0.83, p&lt;0.001 for all 3). A uniphasic MV atrial systolic inflow signal was present in 20/21 fetuses at 7+1-9+0 weeks, whereas, biphasic MV inflow was seen in 45% at 9+1-10+0 , 76% at 10+1-11+0 , 95% at 11+1-13+0 and 100% after 13+1 weeks GA. Inflow duration was significantly longer (146.9±25.4 vs 85.2±12.6ms, p&lt;0.001) and HR was lower (160±9 vs 170±10 bpm, p&lt;0.001) in fetuses with a biphasic flow pattern. ET demonstrated a weak relationship with GA (R2=0.41) and no relationship with HR, IVRT,or IVRT/R-R, and the systolic time showed a nonlinear trend of decreasing with GA (R2=0.46). Conclusions: In the 7-15 week fetus, improvements in relaxation suggested by decreasing IRT, decreasing HR, and, to a lesser extent, decreasing systolic time likely contribute to increasing inflow duration and to early ventricular filling.

Correlation between beat-to-beat blood pressure variability and arterial stiffness in healthy adults in the cold pressor test

Blood pressure variability has a great effect on the progression of arterial stiffness, which has increasingly become a hot research topic recently. In this study, beat-to-beat recordings of blood pressure (BP), heart rate, cardiac output, total peripheral resistance, and left ventricular ejection time during the cold pressor test (CPT) were analyzed together. We recruited 101 young Chinese subjects (aged 21-33) with no known history of high BP into the study. We found that the mean level of beat-to-beat BP and the average real variability and successive variation of beat-to-beat diastolic BP variability in the CPT showed significant correlations with pulse wave velocity (PWV) (r=0.22-0.34, P<0.05). In addition, we also found correlations between beat-to-beat heart rate and heart rate variability indices and PWV in each phase of the CPT. At the same time, the standard deviation of the R-R intervals and square root of the mean squared difference of successive R-R intervals in the cold stimulus phase also showed significant correlations with PWV (r=0.23-0.24, P<0.05). In conclusion, the level and variability of beat-to-beat BP have a strong influence on arterial stiffness.

A validation study of electrical cardiometry in pregnant patients using transthoracic echocardiography as the reference standard

To validate electrical cardiometry (EC) in pregnant patients using transthoracic echocardiography (TTE) as the reference standard. To improve EC accuracy via a one-time, measurement of left ventricular outflow tract (LVOT) diameter. 44 non-laboring, resting women with singleton, viable pregnancies underwent simultaneous EC and TTE measurements. Data were analyzed using Bland-Altman analysis. Entry multiple regression with stepwise elimination was used to develop a model for improved prediction of stroke volume by TTE (SVTTE) using EC. Bootstrapping and an 11-fold cross validation were used to test the model. Heart rate by TTE and EC had a mean bias of 3.3beats/min and mean percentage error of 10.7%. Envelope time and left ventricular ejection time had a mean bias of -4.9ms and mean percentage error 12.7%. Stroke volumes by the two techniques had a mean bias of 15.6mL and mean percentage error of 43.7%. A model, SVEC_Modified, predicting SVTTE was developed using LVOT area, stroke volume by electrical cardiometry and weight. SVTTE and SVEC_Modified had a mean bias of -0.83mL and mean percentage error of 22%. EC accurately measures heart rate and duration of systole when compared with TTE. Stroke volume measurements correlate but have a high bias and percentage error. Knowledge of LVOT area, by a one-time, measurement with TTE, could improve prediction of stroke volume by EC.

Impact of Ivabradine on Central Aortic Blood Pressure and Myocardial Perfusion in Patients With Stable Coronary Artery Disease.

Treatment of hypertensive patients with β-blockers reduces heart rate and decreases central blood pressure less than other antihypertensive drugs, implying that reducing heart rate without altering brachial blood pressure could increase central blood pressure, explaining the increased cardiovascular risk reported with β-blocker. We describe a randomized, double-blind study to explore whether heart rate reduction with the If inhibitor ivabradine had an impact on central blood pressure. We included 12 normotensive patients with stable coronary artery disease, heart rate ≥70 bpm (sinus rhythm), and stable background β-blocker therapy. Patients received ivabradine 7.5 mg BID or matched placebo for two 3-week periods with a crossover design and evaluation by aplanation tonometry. Treatment with ivabradine was associated with a significant reduction in resting heart rate after 3 weeks versus no change with placebo (-15.8±7.7 versus +0.3±5.8 bpm; P=0.0010). There was no relevant between-group difference in change in central aortic systolic blood pressure (-4.0±9.6 versus +2.4±12.0 mm Hg; P=0.13) or augmentation index (-0.8±10.0% versus +0.3±7.6%; P=0.87). Treatment with ivabradine was associated with a modest increase in left ventricular ejection time (+18.5±17.8 versus +2.8±19.3 ms; P=0.074) and a prolongation of diastolic perfusion time (+215.6±105.3 versus -3.0±55.8 ms with placebo; P=0.0005). Consequently, ivabradine induced a pronounced increase in Buckberg index, an index of myocardial viability (+39.3±27.6% versus -2.5±13.5% with placebo; P=0.0015). In conclusion, heart rate reduction with ivabradine does not increase central aortic blood pressure and is associated with a marked prolongation of diastolic perfusion time and an improvement in myocardial perfusion index. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004779-35.

Type-specific orthostatic hemodynamic response of hypertensive diseases in pregnancy.

Posture changes may differ between types of hypertensive disease. The aim is to evaluate the orthostatic response of impedance cardiography (ICG) measurements in uncomplicated and hypertensive pregnancies. Measurements were performed in supine and standing position in 202 women: 41 uncomplicated pregnancies (UP), 59 gestational hypertension (GH), 35 early-onset (EPE, < 34 weeks) and 67 late-onset (LPE, ≥ 34 weeks) preeclampsia were assessed. Measurements were recorded of heart rate, blood pressure, aortic flow parameters, cardiac output, pre-ejection period and left ventricular ejection time. Overall, orthostatic shifts were different between all groups (P < 0.001). UP was different from the hypertensive complicated gestations in the orthostatic change of the aortic acceleration. In contrast to patients with preeclampsia, those with GH had an increased blood pressure and Heather index, and stable pre-ejection period after posture change. EPE differed from LPE by change in blood pressure and aortic flow parameters. In addition to static ICG-measurements, orthostatic shifts improved group characterization from 57.4% to 65.8%. The orthostatic response is altered in hypertensive pregnancies. ICG measurements in the upright as well as during an orthostatic test might have the potential to improve the discriminative yield between hypertensive diseases in pregnancy.