Index Of Left Ventricular Relaxation Research Articles

Manipulation of Left Ventricular Loading Conditions is Necessary to Identify Diastolic Dysfunction in Swine with Repetitive Pressure Overload‐Induced HFpEF

ObjectiveDiagnosis of heart failure with preserved ejection fraction (HFpEF) is often complicated by the fact that many patients exhibit normal left ventricular (LV) mechanics at rest with a reduction in diastolic compliance that is only revealed when loading conditions are altered (e.g., during exercise stress). In an effort to identify parameters of diastolic function that could be utilized to detect alterations in compliance without manipulation of LV loading conditions, we utilized invasive hemodynamic analysis and speckle‐tracking echocardiography (STE) to assess diastolic strain and stiffness in swine with repetitive pressure overload (RPO)‐induced HFpEF.MethodsSwine (n=13) were subjected to 2‐weeks of RPO via daily intravenous administration of phenylephrine (PE; 400 ug/min; 1 hour/day) through an indwelling jugular vein catheter. Indices of LV relaxation as well as LV minimum and end‐diastolic pressure were obtained invasively before and after RPO at rest and during transient PE‐induced alterations in loading conditions. STE (Vivid 9; GE) was also performed throughout a single cardiac cycle to collect circumferential diastolic strain data, which were used alongside echocardiography‐derived measurements of chamber radius and wall thickness as well as catheter‐derived measurements of LV pressure to calculate regional and global circumferential subendocardial diastolic stiffness before and after RPO.ResultsCompared with baseline measurements, 2‐weeks of RPO did not significantly increase the time constant of LV relaxation (Tau; Figure A) or decrease the rate of LV pressure change during isovolumic relaxation (dP/dtmin; Figure B). Circumferential subendocardial stiffness derived via STE across a single cardiac cycle at rest was also unaffected by RPO (Figure C), despite a significant reduction in diastolic compliance that was revealed by construction of two‐point end‐diastolic pressure‐volume curves (Figure D) after manipulation of loading conditions (Figure E). Interestingly, single‐cycle STE‐derived stiffness measurements made during acute pressure overload were also similar at baseline and after RPO due to persistent elevations in LV minimum diastolic pressure during PE infusion at both timepoints.ConclusionsAlthough reductions in LV diastolic compliance are evident after chronic RPO when loading conditions are manipulated, abnormalities in LV mechanics are not exhibited at rest even when STE is used to assess diastolic stiffness throughout a single cardiac cycle. These findings highlight the challenges associated with identification of myocardial stiffening at rest in patients with HFpEF and reinforce the importance of studying LV mechanics under variable loading conditions.

Hypertension-mediated organ damage in masked hypertension.

Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring. Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg). Evidence of hypertension-mediated organ damage was compared in patients with sustained normotension, masked hypertension, and sustained hypertension based on measurements by HBPM, daytime ABPM, and 24-h ABPM. The 420 participants averaged 48 (12) [mean (SD)] years of age; the average clinic BP was 130 (13)/81 (8) mmHg. In individuals with masked hypertension diagnosed by HBPM, indexed LV mass, relative wall thickness, and e' and E/e' (indices of LV relaxation), were generally intermediate between values observed in normotensives and sustained hypertensive patients, and were significantly greater in masked hypertension than normotensives. Similar trends were observed when masked hypertension was diagnosed by ABPM but a diagnosis of masked hypertension was not as reliably associated with LV remodeling or impaired LV relaxation in comparison to normotensives. There were trends towards greater likelihoods of detectable urinary microalbumin and coronary calcification in masked hypertension than in normotensives. These results support previous studies demonstrating early hypertension-mediated organ damage in patients with masked hypertension, and suggest that HBPM may be superior to ABPM in identifying patients with masked hypertension who have early LV remodeling and diastolic LV dysfunction.

Effect of soya phosphatidylcholine and possible underlying mechanism on ischemia/reperfusion injury in isolated perfused rat heart: an experimental and computational study.

This study was designed to assess the effect of soya phosphatidylcholine (SPC) against ischemia/reperfusion (I/R) injury and the possible underlying mechanism using experimental and computational studies. I/R injury was induced by global ischemia for 30min followed by reperfusion for 120min. The perfusion of the SPC was performed for 10min before inducing global ischemia. In the mechanistic study, the involvement of specific cellular pathways was identified using various inhibitors such as ATP-dependent potassium channel (KATP) inhibitor (glibenclamide), protein kinase C (PKC) inhibitor (chelerythrine), non-selective nitric oxide synthase inhibitor (L-NAME), and endothelium remover (Triton X-100). The computational study of various ligands was performed on toll-like receptor 4 (TLR4) protein using AutoDock version 4.0. SPC (100 μM) significantly decreased the levels of cardiac damage markers and %infarction compared with the vehicle control (VC). Furthermore, cardiodynamics (indices of left ventricular contraction (dp/dtmax), indices of left ventricular relaxation (dp/dtmin), coronary flow, and antioxidant enzyme levels were significantly improved as compared with VC. This protective effect was attenuated by glibenclamide, chelerythrine, and Triton X-100, but it was not attenuated by L-NAME. The computational study showed a significant bonding affinity of SPC to the TLR4-MD2 complex. Thus, SPC reduced myocardial I/R injury in isolated perfused rat hearts, which might be governed by the KATP channel, PKC, endothelium response, and TLR4-MyD88 signaling pathway.

Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e').

Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (β=-0.33, P<0.01) and LV ejection fraction (LVEF) (β=0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) (β=0.37, P<0.001) and LVMDP (β=0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.

Left ventricles of aging athletes: better untwisters but not more relaxed during exercise.

With an aging population and the increasing prevalence of heart failure with preserved ejection fraction, developing strategies to prevent diastolic dysfunction is crucial. Regular endurance training has been suggested to be one such strategy. However, the underlying mechanisms of training, including the effect on left ventricular (LV) untwist, which promotes LV filling, are unclear and studies exploring the heart during exercise in the aging heart are lacking. Cardiopulmonary exercise testing with speckle tracking echocardiography was realized in male subjects: 16 young athletes (YA), 19 young controls (YC), 22 middle-aged athletes (MA) with a lifelong history of endurance training, and 20 middle-aged controls (MC). During exercise, the early filling was lower in MC compared to YC, whereas it was preserved between YA and MA. At exercise, peak untwisting rate/peak twist ratio and the percentage of untwist during isovolumic relaxation time were decreased in senior groups but higher in YA and MA compared to age-matched controls. Early diastolic filling reserve correlated with untwisting rate/peak twist reserve in YA and MA (R 2=0.22, p<0.05) but not in controls. LV relaxation indices in athletes at rest and during exercise were not improved compared to age-matched controls. LV intrinsic relaxation was similarly lower with age, independently of training, while the age-related decrease of untwist during exercise was lower with lifelong exercise training. The preservation of untwist mechanics in MA could thus sustain the early filling during exercise. Further studies are needed to confirm the role of exercise training as a preventive strategy for diastolic dysfunction and heart failure.

0176 : LV diastolic function and mechanics adaptation during the transition from rest to exercise

During the transition from rest to exercise, heart rate (HR) immediately increase to provide a sufficient O2 delivery to active muscle. This adaptation of HR induces a dramatically decrease of left ventricular (LV) filling time, that requires a very fast adaptation of the LV diastolic function to maintain LV filling. Diastolic function depends on many factors including intrinsic cardiomyocytes relaxation, LV filling pressure and also LV untwisting that occurs very early in diastole. However, the kinetics of these underlying mechanisms of LV diastolic function during the transition from rest to exercise remain to be explore. 25 young males (23±4 years) were recruited. Each subject performed 5 similar 4-min constant load exercises on a dedicated ergometer in a semi-supine position. 2D cine loops were recorded every 15s from different echocardiographic views. LV longitudinal diastolic strain rate (SrL diast ), an index of LV relaxation, and LV end-diastolic volume (LV-EDV) were assessed from an apical 4-chamber view. LV rotations, twist and its subsequent untwist were assessed from basal and apical short-axis views. The global strain imaging diastolic index was used as a sensitive index of LV filling pressures. At the onset of exercise, LV-EDV increased during the first 60s despite rapid increase of HR. This adaptation was firstly driven by rapid increase of LV filling pressure in the first 15s, probably due to venous return induced by the pedaling. LV filling was also facilitated by a rapid increase of cardiomyocyte relaxation as evidenced by the increase of SrL diast . Moreover, the increase in LV twist and its subsequent untwist was major during the first min of exercise and increase of the untwisting rate/twist ratio until 90s underlined an improvement in elastic recoil very early in diastole. These findings bring new and original data regarding the adaptation of the LV diastolic function and mechanics during the transient from rest to exercise in healthy subjects. The author hereby declares no conflict of interest

Echocardiographic evaluation and comparison of the effects of sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction scheduled for coronary artery bypass grafting surgery

Background Effect of inhalational anesthetics on diastolic function in humans is still controversial, although inhalational anesthetics have been shown to have negative lusitropic action in experimental studies, which were explained by interference of inhalational anesthetics with calcium homeostasis. Aim This prospective randomized study aims to evaluate and compare the effects of sevoflurane and desflurane on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. Patients and methods After approval from the local ethics committee and informed consent, 24 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative transthoracic echocardiographic diagnosis of impaired relaxation or grade 1 diastolic dysfunction. Anesthetic induction was standardized in both groups. Patients randomly received 1 MAC of sevoflurane ( n = 12) or desflurane ( n = 12) for maintenance of anesthesia. Hemodynamic parameters and transesophageal echocardiography (TEE) derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept within normal range throughout the study period to exclude the effect of the loading conditions on diastolic function. Results The two study drugs significantly reduced the systemic vascular resistance index with a significant increase in the cardiac index. Hemodynamic changes measured by invasive arterial line and pulmonary artery catheter were comparable between the two groups. In terms of LV relaxation indices, the two agents led to a significant improvement in diastolic function. Transmitral and tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of the two agents on diastolic relaxation parameters was comparable. Conclusion Sevoflurane and desflurane appear to improve LV relaxation. This can be explained by a significant reduction in afterload produced by these vapors. The positive effect of these inhalational agents on LV relaxation can have a beneficial effect on the anesthetic management of patients with diastolic dysfunction.

Relationship of Myocardial Fibrosis to Left Ventricular and Mitochondrial Function in Nonischemic Dilated Cardiomyopathy—A Comparison of Focal and Interstitial Fibrosis

BackgroundMitochondrial damage is associated with histologic myocardial fibrosis. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) can be used to identify focal fibrosis. We examined whether myocardial fibrosis on CMR and collagen volume fraction (CVF) from biopsies correlated with left ventricular (LV) and mitochondrial function in patients with nonischemic dilated cardiomyopathy (DCM). Methods and ResultsFifty-nine DCM patients underwent CMR, cardiac catheterization, and endomyocardial biopsy. Minimum first derivative of LV pressure (LVdP/dtmin) was measured as an index of LV relaxation. Mitochondrial RNA expression was also analyzed. For quantitative analysis of myocardial fibrosis, percentage LGE (%LGE) and CVF were calculated. Patients were divided into 2 groups on the basis of the presence (LGE group; n = 27) or absence (non-LGE group; n = 32) of LGE. Mean CVF and absolute value of LVdP/dtmin were significantly higher and lower, respectively, in the LGE group than in the non-LGE group. Multivariate analysis revealed that %LGE was an independent determinant of LVdP/dtmin. The abundance of mitochondrial enzyme mRNA was significantly lower in the LGE group. ConclusionsNoninvasive CMR imaging is more useful in predicting diastolic dysfunction than invasive histologic assessments. In addition, it might indicate mitochondrial dysfunction in DCM.

Association of left atrial enlargement with left ventricular hypertrophy and diastolic dysfunction: A tissue Doppler study in echocardiographic practice

Background. Left atrial (LA) enlargement is a powerful risk factor for cardiovascular diseases; little information is available about its prevalence and correlates in subjects free of overt cardiac disease seen in echocardiographic practice. Aim. We evaluated the prevalence of LA enlargement (LAE) and the relationship with left ventricular (LV) mass and diastolic function in subjects with preserved LV systolic function referred to an echocardiographic study for routine clinical indications. Methods. 1104 subjects (mean age 58 ± 16 years, 46% men, 57% hypertensives) underwent a comprehensive echo-Doppler examination. LAE and LV hypertrophy (LVH) were defined as LA volume index (LAVI) >29 ml/m2 and LV mass index (LVMI) >50 g/h2.7, respectively. Abnormalities of LV relaxation and LV filling were diagnosed by age-related thresholds of lateral annular velocity (Ei) and by early mitral flow velocity to Ei ratio (E/Ei) ≥16, respectively. Results. Overall, 10% of echocardiographic examinations fulfilled the criteria for LAE, 46% for LVH, 45% for altered LV relaxation and 5% for altered LV filling index. LVH progressively increased from 25% to 75% across LAVI quartiles. More patients in the highest quartile exhibited abnormal indexes of LV relaxation and LV filling compared with lower quartiles. In multivariate analysis, LV mass index (β = 0.408), age (β = 0.188), E/Ei ratio (β = 0.140) and Ei (β = 0.140) emerged as major correlates of LAE (p at least <0.01 for all). Conclusions. LAE is a frequent finding in patients with preserved systolic function seen in current practice; this abnormality is strongly related to LVH and to diastolic dysfunction. Early detection of LAE may identify patients at higher cardiovascular risk and promote appropriate prevention strategies.

Competing risks of heart failure with preserved ejection fraction in diabetic patients

The prevalence of heart failure with preserved ejection fraction (HFpEF) has increased in the past two decades, and diabetes mellitus (DM) is frequently associated with HFpEF. Although it has been demonstrated that left ventricular (LV) diastolic and vascular functional abnormalities are generally observed in HFpEF, it remains to be clinically elucidated how an asymptomatic stage progresses to symptomatic HFpEF in DM patients. We aimed to identify risk factors associated with incident HFpEF in DM patients and to evaluate the contribution of LV relaxation and compliance to the development of HFpEF. The study included 544 consecutive Japanese DM patients with ejection fraction ≥50%. Patients with coronary artery disease or serum creatinine ≥2.0 mg/dL were excluded. Multiple logistic regression analysis revealed that obesity, female gender, anaemia, and impaired LV compliance were independently associated with the prevalence of HFpEF, and that age, LV mass index, an index of LV relaxation, estimated glomerular filtration rate, and history of hypertension were not. There was no difference in haemoglobin A1c or brachial-ankle pulse wave velocity between the DM patients with and without HFpEF. This study suggests that exacerbation of LV compliance impairment, rather than of relaxation abnormality or vascular stiffening, plays a crucial role in the induction of HFpEF in DM patients regardless of the severity of DM and renal dysfunction. Anaemia and obesity may also contribute to the transition from asymptomatic stage to symptomatic HFpEF even without further progression of LV diastolic dysfunction.

Role of left ventricular untwisting in diastolic dysfunction after long duration exercise

Numerous studies have reported that long duration exercise induces transient left ventricular (LV) dysfunction. Using 2D-strain echocardiography, we aimed to describe cardiac mechanics following 2 h of exercise. We focused especially on LV twist since untwisting is crucial in the development of intraventricular pressure gradient, a key element of LV early filling. Twenty healthy males (20-41 years) underwent a resting echocardiography including a 2D-strain evaluation based on velocity vector imaging before and after 2-h of cycling at a moderate intensity. Measurements included LV longitudinal, radial and circumferential strains, and LV rotations and twist. After the prolonged exercise, the depressed diastolic function (peak E: 77.5 ± 11.4 vs. 71.9 ± 10.9, P < 0.01) was associated with a delay in peak untwisting velocity (110 ± 14 vs. 119 ± 14% of systolic duration, P < 0.05), whereas LV peak diastolic strain rates, indexes of LV relaxation, were unchanged. LV global systolic function and LV peak systolic strain rates remained normal after the exercise (fractional shortening: 36.8 ± 2.8 vs. 36.9 ± 5.7, NS). In conclusion, the present study gives new insight into cardiac dysfunction following long duration exercise. It demonstrates that depressed diastolic function is associated with delayed untwisting velocity, but depressed LV relaxation and contractility following exercise remains controversial.

Echocardiographic evaluation and comparison of the effects of isoflurane, sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction

This prospective randomized study aims to evaluate and compare the effects of isoflurane, sevoflurane and desflurane (study drugs) on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. After approval of the local ethics committee and informed consent, 45 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative Transthoracic Echocardiographic diagnosis of impaired relaxation or Grade 1 Diastolic Dysfunction. They randomly received fentanyl and midazolam anesthesia with 1 MAC of isoflurane (n=16), sevoflurane (n=14) or desflurane (n=15). Hemodynamic parameters and TEE derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept constant throughout the study period to exclude the effect of the loading conditions on diastolic function. Four patients in the sevoflurane group and three in the desflurane group were excluded from the study, after baseline TEE examination revealed normal diastolic filling pattern. All the three study drugs significantly reduced the systemic vascular resistance index with a significant increase in cardiac index. Mean arterial pressure was reduced by all the drugs, although the decrease was not statistically significant. Hemodynamic changes were comparable between all the three groups. In terms of LV relaxation indices, all three agents led to a significant improvement in diastolic function. Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of all three agents on diastolic relaxation parameters was comparable. In conclusion , Isoflurane, sevoflurane and desflurane, do not appear to have a detrimental effect in patients with early diastolic dysfunction. On the contrary, these inhalational agents actually improve the LV relaxation. A significant reduction in afterload produced by these vapors can be a possible reason for these findings. The positive effect of these inhalational agents on LV relaxation can have a profound effect on the perioperative anesthetic management of patients with diastolic dysfunction.

Influence Of Left Ventricular Diastolic Function On Ventilatory Responses During Exercise In Healthy Individuals

Healthy aging is associated with changes in left ventricular (LV) diastolic function, namely a prolongation of LV relaxation and increased filling pressures. This could influence ventilation through afferent cardiac pulmonary receptors sensitive to stretch or pressure and/or to changes in lung compliance. Such cardio-pulmonary interdependence may be accentuated with exercise. PURPOSE: To determine if indices of LV diastolic function influence ventilation, breathing pattern and gas exchange during exercise in healthy adults, and to determine if these associations are age related. METHODS: 103 adults (age: 50±2, range 22-76yr, 42 females, VO2peak: 34.8±0.8 ml/kg/min, FEV1: 105±1 %pred) underwent echocardiography and cardiopulmonary exercise testing. Isovolumic relaxation time (IVRT) and the ratio of peak early mitral inflow velocity to peak early mitral annular velocity (E/E') were used as indices of LV relaxation and filling pressure. Respiratory rate (RR), tidal volume (VT), ventilation (VE), all indexed to individual vital capacities (VC), as well as ventilatory efficiency (VE/VCO2) and VT/TI, an index of VE drive, were obtained during exercise. RESULTS: Age was positively correlated with IVRT and E/E' (r=0.32, 0.58, p<0.001). An increase in LV filling pressure was positively associated with VE/VC at a matched submaximal workload (r=0.21, p<0.05), and with RR/VC and VE/VCO2 at peak exercise (r=0.21, 0.26, p<0.05). Prolonged LV relaxation was associated with VE/VC, VE/VCO2 and VT/TI at the matched workload (r=0.35, 0.26, 0.21, p<0.05), and with RR/VC, VT/VC and VE/VCO2 at peak exercise (r=-0.22, 0.23, 0.22, p<0.05). The relationship between diastolic function and ventilatory function was not independent of age at the submaximal workload. The associations between RR/VC and LV filling pressure and relaxation, as well as the association between VE/VC and filling pressure were independent of age at peak exercise. CONCLUSION: Resting measures of LV diastolic function are associated with breathing pattern, gas exchange and ventilation, however only measures of breathing pattern at peak exercise appeared to be associated with diastolic function independently of age. NIH Grant HL71478.

Acute left ventricular dilatation and shock-induced myocardial dysfunction*

Whether cardiac ventricles can acutely dilate during septic myocardial dysfunction. A prospective echocardiographic study was performed to assess changes of left ventricular dimensions over time in patients with septic shock. A 20-bed surgical intensive care unit of Pitié-Salpêtrière university hospital in Paris. Forty-five patients were studied over the first 10 days of septic shock. None. Left ventricular end-diastolic area (LVEDA), fractional area change (FAC), velocity time integral of the aortic flow, echocardiographic indices of left ventricular relaxation, and cardiac troponin I (cTnI) were measured at day 1, 2, 3, 4, 7, and 10. Three groups were defined: 29 patients without increased cTnI and cardiac impairment (group 1), eight patients with increased cTnI and left systolic ventricular dysfunction (group 2), and eight patients with increased cTnI and isolated impairment of left ventricular relaxation (group 3). At day 1, LVEDA was significantly higher in group 2 (13 +/- 3 cm/m, p < 0.05) compared with groups 1 (10 +/- 2 cm/m) and 3 (11 +/- 2 cm/m). LVEDA did not change in groups 1 and 3. In group 2, LVEDA and FAC returned within 10 days to values observed in groups 1 and 2. A significant correlation was found between aortic velocity time integral and LVDEA (r =.78, p = 0.022) and FAC (r =.89, p = 0.003) only in group 2. Acute and reversible left ventricular dilation accompanies septic shock-induced systolic left ventricular dysfunction. When septic myocardial abnormalities are limited to reversible impairment of left ventricular relaxation, left ventricular dimensions remain unchanged.

Left Ventricular Systolic and Diastolic Function in Asymptomatic Patients With Moderate Aortic Stenosis

Tissue Doppler imaging (TDI) has improved the ability to detect subclinical changes in left ventricular (LV) function. The aim of this study was to investigate if asymptomatic patients with moderate aortic stenosis (AS) had impaired LV systolic and diastolic function. Fifty patients (mean age 65 +/- 12 years) recruited into the multicenter Simvastatin + Ezetimibe in Aortic Stenosis (SEAS) study with aortic peak velocities of 2.5 and 4.0 m/s were compared with 26 healthy subjects (mean age 64 +/- 12 years) (p = NS). Peak systolic tissue velocities and strain were measured at 8 LV locations and averaged. Early diastolic tissue velocity from the septal mitral annulus (E'sep) was measured as an index of LV relaxation. The ratio of early diastolic transmitral pulsed Doppler (E) to E'sep (E/E'sep) was calculated as an index of LV filling pressure. Peak systolic tissue velocity (4.1 +/- 1.0 vs 4.8 +/- 1.1 cm/s, p <0.01) and strain (-16.6 +/- 2.7% vs -17.9 +/- 2.0%, p <0.05) were decreased in patients with AS compared with controls. E'sep was decreased (4.9 +/- 1.0 vs 5.8 +/- 1.3 cm/s, p <0.01) and E/E'sep was increased (17.4 +/- 9.7 vs 11.7 +/- 3.8, p <0.01) in the AS group compared with the control group. In conclusion, asymptomatic patients with moderate AS have impaired LV systolic function as measured by reduced peak systolic tissue velocity and strain. Augmented LV filling pressure measured by E/E'sep and impaired LV relaxation measured by reduced E'sep also indicate diastolic dysfunction in these patients.

IVRT′/IVRT Index Is a Useful Tool for Detection of Elevated Left Ventricular Filling Pressure in Patients with Preserved Ejection Fraction

Deterioration of active relaxation results in prolongation of isovolumteric relaxation time (IVRT), however, when left ventricular filling pressure elevates, mitral valve opens earlier and IVRT shortens. This shortening is not seen when IVRT is measured with tissue Doppler imaging (IVRT'). Then, IVRT' prolongs with the deceleration of active relaxation independent of left ventricular filling pressure. We hypothesized that IVRT' reflects the relaxation rate, thus, the ratio of IVRT' to IVRT may possibly detect left ventricular filling pressure elevation. The group of 39 subjects (aged 64 +/- 5 years) with preserved ejection fraction (EF > 50%) underwent combined echocardiographic and hemodynamic examinations. Echocardiographic parameters of mitral inflow and mitral annular motion were correlated with invasive indices of left ventricular relaxation and filling pressure. Time constant of isovolumetric pressure decline (tau) correlated closely with IVRT' (r = 0.73, P < 0.001) but not with early diastolic velocity of mitral annulus (E') (r =-0.207, P = 0.206). The best parameter correlating with M-LVDP was IVRT'/IVRT (r = 0.694, P < 0.001, M-LVDP = 7.7 x IVRT'/IVRT + 5.1). A weaker relation was also noted between the ratio of early mitral peak inflow velocity to early diastolic velocity of mitral annulus (E/E') and M-LVDP (r = 0.469, P < 0.001). The relationships between standard Doppler parameters and left ventricular diastolic pressures were uniformly poor. The study demonstrated that IVRT' may serve as a surrogate of left ventricular active relaxation. IVRT'/IVRT index may be applied to estimate left ventricular filling pressure.

Proof-of-concept trial to evaluate haemoglobin based oxygen therapeutics in elective percutaneous coronary revascularisation. Rationale, protocol design and haemodynamic results

To test the hypothesis that intracoronary infusion of pre-oxygenated HBOC-201 during brief, total coronary artery occlusion would preserve left ventricular function. Immediately following a successful PCI, the target coronary artery was occluded without ("dry occlusion")--or with--infusion of pre-oxygenated HBOC-201 distal to the stent via the guidewire shaft of an over-the-wire balloon for up to three minutes at an infusion rate of 48 ml/min. A cross-over design was applied. Early signs of myocardial ischaemia were evaluated by left ventricular pressure-volume loops and intracoronary ECG. A 12-lead Holter ECG was activated before the PCI and deactivated four hours after the study period. Primary endpoints were change in left ventricular relaxation indices and in the sum of ST segment deviations. None of the measured parameters differed significantly from their respective baseline values during HBOC-201 infusion. By contrast, ejection fraction (EF), cardiac output (CO) and minimal rate of LV pressure change (dP/dTMIN) decreased significantly and the end diastolic pressure (EDP) and time constant of relaxation increased significantly during dry occlusions (P<0.05). The end diastolic pressure-volume relationship (EDPVR) at the fixed pressure level of 30 mmHg (V30), an index of myocardial compliance, reflected greater myocardial stiffness during dry occlusions compared to occlusions with HBOC-201 infusion. Intracoronary infusion of oxygenated HBOC-201 is capable of preserving left ventricular function, likely through maintenance of myocardial oxygenation. It is hypothesised, that in an acute setting, HBOC-201 could serve as an oxygen bridge to reperfusion by PCI extending the "golden" time period during which permanent myocardial damage is unlikely.

Higher circulating 4-hydroxynonenal–protein thioether adducts correlate with more severe diastolic dysfunction in spontaneously hypertensive rats

Objective: Accumulating evidence supports a role of 4-hydroxynonenal (4HNE) in oxidative-stress related diseases, but its specific contribution to disease development remains to be clarified. Further to our finding of high circulating 4HNE–protein thioether adducts (4HNE-P) in spontaneously hypertensive rats (SHRs), we aimed at correlating 4HNE-P with cardiac function and testing the impact of antioxidant therapy.Materials and Methods: The lipoperoxidation inhibitor probucol (10 mg/kg/day) or vehicle (corn oil) were administered daily (i.p.) for 4 weeks in 18-week-old SHRs (9 rats/group). Cardiac functions were assessed by echocardiography and 4HNE-P by gas chromatography/mass spectrometry.Results: Diastolic dysfunction worsened in SHRs receiving vehicle as reflected by changes (P < 0.05) in indexes of left ventricular relaxation (increased isovolumic relaxation time) and compliance (increased E-wave deceleration rate; EDR). Higher circulating 4HNE-P correlated with diastolic dysfunction (EDR: R2 = 0.518; P < 0.001) and heart rate (R2 = 0.225; P < 0.05). Probucol prevented the deterioration of diastolic function, while lowering the mean and median of circulating 4HNE-P by 21% and 35%, respectively.Conclusion: Collectively, these results support a role for 4HNE in the pathophysiological events linked to disease progression in SHRs.

Left Atrial Contractile Function Is Persistently Augmented in Newly Diagnosed Asymptomatic Hereditary Hemochromatosis Subjects Despite One Year Therapy

We have previously shown that left atrial (LA) contractile function in newly diagnosed asymptomatic hereditary hemochromatosis (HH) subjects with modest iron overload is significantly augmented than control subjects despite the lack of detectable left ventricular (LV) relaxation abnormalities. However, the therapeutic effect of phlebotomy in this population has never been monitored. We monitored LA function and LV diastolic function of this population using 2D and Doppler echocardiography over 12-month therapy. We recruited 22 newly diagnosed asymptomatic HH subjects ages 48±11 (mean±SD). All HH subjects had HEF C282Y homozygosity and and underwent follow up echocardiography at 6-month and 12-month of phlebotomy treatment. The HH subjects showed significantly higher normalized active emptying volume (AEV-N; 7.5±2.8 vs 5.5±1.9 ml/m2), active emptying fraction (AEF; 41.6±10.0 vs 34.2±10.2%), ejection force (AF; 15.2±5.9 vs 10.3±4.1 kdyne), and kinetic energy (KE; 25.1±15.9 vs 14.0±7.1 kerg) of LA at baseline (data are HH vs controls, P<0.05 for all). Despite the significant reduction of iron overload during 12-month therapy, no significant changes in the LA contractile function were noted in HH subjects [AEV-N(ml/m2);8.4±5.6, AEF(%);43.8±13.7, AF(kdyne);14.5±8.3, KE(kerg);28.1±14.8, data are at 12-month(n=18)]. The indices of LV relaxation were not changed. Our results suggest that augmentation of LA contractile function is persistent in asymptomatic HH subjects despite one year therapy of iron removal. Further investigation is needed to determine the therapeutic effect.

Preload Dependency of the Time Interval Between the Onset of Mitral Inflow and the Early Diastolic Annular Motion A Hemodialysis-Related Preload Reduction Study

The novel parameter T(E-E'), which is the time interval between the onset of the early diastolic mitral inflow velocity (E) and the early diastolic mitral annular velocity (E'), is reported to be related to the constant of the left ventricular (LV) relaxation, and T(E-E') is also reported to be useful for predicting the LV filling pressure. To investigate the effect of preload reduction via hemodialysis on T(E-E'), 28 pairs of echocardiographic evaluations were performed just before and immediately after hemodialysis, including the measurement of the T(E-E') as well as measurement of the conventional echocardiographic parameters. The baseline T(E-E') was 17.9 +/-28.1 ms, which correlated with the ratio of E/E' (r=0.49, p=0.008). After hemodialysis, T(E-E') was shortened to -3.2+/-34.1 ms, which was a significant change from baseline (p=0.001). As T(E-E') is a preload dependent parameter, the intravascular volume status should be taken into account when the clinical application of T(E-E') is considered as an index of LV relaxation.