Indices Of LV Function Research Articles

Predicting postoperative systolic dysfunction in mitral regurgitation: CT vs. echocardiography.

Volume overload from mitral regurgitation can result in left ventricular systolic dysfunction. To prevent this, it is essential to operate before irreversible dysfunction occurs, but the optimal timing of intervention remains unclear. Current echocardiographic guidelines are based on 2D linear measurement thresholds only. We compared volumetric CT-based and 2D echocardiographic indices of LV size and function as predictors of post-operative systolic dysfunction following mitral repair. We retrospectively identified patients with primary mitral valve regurgitation who underwent repair between 2005 and 2021. Several indices of LV size and function measured on preoperative cardiac CT were compared with 2D echocardiography in predicting post-operative LV systolic dysfunction (LVEFecho <50%). Area under the curve (AUC) was the primary metric of predictive performance. A total of 243 patients were included (mean age 57 ± 12 years; 65 females). The most effective CT-based predictors of post-operative LV systolic dysfunction were ejection fraction [LVEFCT; AUC 0.84 (95% CI: 0.77-0.92)] and LV end systolic volume indexed to body surface area [LVESViCT; AUC 0.88 (0.82-0.95)]. The best echocardiographic predictors were LVEFecho [AUC 0.70 (0.58-0.82)] and LVESDecho [AUC 0.79 (0.70-0.89)]. LVEFCT was a significantly better predictor of post-operative LV systolic dysfunction than LVEFecho (p = 0.02) and LVESViCT was a significantly better predictor than LVESDecho (p = 0.03). Ejection fraction measured by CT demonstrated significantly greater reproducibility than echocardiography. CT-based volumetric measurements may be superior to established 2D echocardiographic parameters for predicting LV systolic dysfunction following mitral valve repair. Validation with prospective study is warranted.

Cardiac Function Evaluation after SARS-CoV-2 mRNA Vaccination in Children and Adolescents: A Prospective Speckle-Tracking Echocardiography Study.

Possible cardiac impairment after SARS-CoV-2 mRNA vaccination is a common driver of parental vaccine hesitancy. We performed a comprehensive echocardiographic evaluation of biventricular function in vaccinated children with or without previous COVID-19 compared to healthy controls. We conducted a single-center, prospective, case-control study enrolling children and adolescents aged 5-18 years attending the pediatric clinic of the University Hospital of Padua from April to June 2022. Three months after receiving the primary mRNA vaccination or booster dose, the patients underwent a cardiac assessment, including standard echocardiography and speckle-tracking echocardiography (STE). A pre-pandemic historical cohort of age- and gender-matched healthy children were used as a control. A total of 39 post-VACCINE cases (24, 61% female), mean age 12.6 ± 2.6 years (range 8-17), were enrolled in the study. Ninety percent (N = 35) of patients were previously healthy. No differences in left ventricular diameters, left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion (TAPSE) were observed between cases and controls. Global longitudinal strain (GLS) was in the normal range in all individuals, with no differences between post-VACCINE cases and controls (-21.7 ± 2.3% vs. 21.2 ± 1.8%; p = 0.338). However, GLS was found to be slightly but significantly reduced in post-VACCINE children with a previous COVID-19 compared to naïve-vaccinated individuals (post-VACCINE+COVID-19: -19.9 ± 1.1% vs. post-VACCINE-only: -22.0 ± 2.3%; p = 0.002). We did not observe an impairment in GLS or in other indices of LV structure or function after mRNA COVID-19 vaccination.

Polarity status of trigger signal during ECG-gating affects parameters of LV function in gated myocardial perfusion SPECT

Introduction and backgroundThe polarity status is one of the important items of specifications of trigger signal from cardiac trigger monitors with two options, either positive or negative. Some systems allow the user to set the polarity of trigger signal before imaging. Efforts should be made to set the polarity status according to the recommendations provided by the manufacturers. In case of inappropriate selection, changes in computation of end-systolic and end-diastolic volumes as well as ejection fraction may occur. ObjectiveTo investigate the effect of the polarity status of trigger signals in synchronization process during 8- and 16-frame gated SPECT imaging on the systolic and diastolic parameters of LV function. MethodsThirty-four patients referred for a myocardial perfusion SPECT were consecutively included in the study. The rest scan for each patient was performed with 8- and 16-frame gating simultaneously with positive trigger signal set by the operator in a cardiac trigger monitor and then repeated after manual selection of negative polarity. In total, the 4 imaging modes acquired were 8-frame/positive-trigger, 16-frame/positive-trigger, 8-frame/negative-trigger, and 16-frame/negative-trigger. All SPECT images were reconstructed and processed with the same values of parameters. Systolic and diastolic indices of LV function were derived in QGS of the Cedars-Sinai software and then were compared using various statistical tests, and a reliability analysis was also performed. ResultsThe age of patients recruited in the study was 58.41 ± 8.94, and 16 (47.1%) males and 18 (52.9%) females. All the correlation coefficients between corresponding parameters in positive and negative trigger signals were statistically significant. The difference between the parameters of systolic function including EF, EDV, and ESV in positive and negative trigger signals was statistically significant in paired sample t test. Likewise, a statistically significant difference was also found between mean phase angle in scans with positive and negative trigger signals by a phase difference of 147.91 (41.0% of an average cardiac cycle) and 149 (41.3% of an average cardiac cycle) degrees in 8- and 16-frame gating modes, respectively. Strong agreement (according to high values of intra-class correlation coefficient) was found for all four pairs. According to Bland-Altman results, an offset of about 3 percentage units was found, both between imaging in 8-frame gating compared to 16-frame gating, higher value in favor of 16-frame gating, and also between imaging with positive polarity trigger compared to negative-polarity trigger, again higher value in favor of positive-polarity triggering. ConclusionThe status of the polarity of trigger signals or similar CTM-camera delays in synchronization process during 8- and 16-frame gated SPECT imaging can be considered as one of the factors that may influence systolic and diastolic indices of LV function

MO429: The Association of Circulating Monocytes Subsets, NK Cells and Lymphocyte Subpopulations With Conventional and Novel Deformation Indices of Left Ventricular Function in CKD Patients With No Established Cardiovascular Disease

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) and chronic kidney disease (CKD) are closely interrelated. Adverse immune responses have been implicated in the pathogenesis of both CVD and CKD [1, 2]. Monocyte subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure [1, 2]. Likewise, the role of lymphocyte subpopulations including natural killer (NK) cells and CD4 + CD25 + regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention [2]. The implication of immune cells subsets in the abnormal myocardial remodeling as universally occurs in CKD patients even without overt CVD, remains to be clarified [3]. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation-related indices of LV function in a cohort of patients with CKD without established CVD. METHOD A total of 35 stable CKD patients (mean age 66 ±12.2 years, 57% males, 20% diabetics) without established CVD were included in the study. Exclusion criteria included the history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16 + and CD14 + CD16++ percentage and absolute number of cells out of the total monocytes and NK cells (CD3 + CD16 + 56+), CD3-CD19 + B lymphocytes, CD3 + CD4 + T cells, CD3 + CD8 + T cells and Tregs (CD4 + CD25 + FoxP3+) absolute values and percentage out of the total lymphocytes were measured by flow cytometry. Simultaneously, conventional [left atrial volume index (LAVI), LV mass index (LVMI), LV end-diastolic volume (LVEDV), E/E’] and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST and UNTWIST] were assessed. RESULTS The mean estimated glomerular filtration rate (eGFR) was 28 ±15 mL/min/1.73 m2 (CKD-EPI) and the mean 24-h proteinuria was 2457 ±2399 mg. The percentage of total blood lymphocytes, as well as both percentage and absolute counts of CD4 + T-cells, were positively correlated with the eGFR (P &amp;lt; 0.05 and &amp;lt; 0.01 respectively) whereas. In addition, both NK cells percentage (P &amp;lt; 0.05) and absolute values (P &amp;lt; 0.01) showed a negative association with proteinuria. Regarding classical indices of LV function, NK counts were negatively associated with LVEDV (P &amp;lt; 0.05). An increased percentage of intermediate CD14++CD16 + monocytes was positively associated with the GRS (P &amp;lt; 0.005). Furthermore, the percentage of T-cells and CD8 + T-cells were positively associated with LV TWIST whereas a positive association was found between the percentage of CD8 + T-cells and more negative values of LV UNTWIST (P &amp;lt; 0.05). No specific significant correlations were observed between the rest immune cells subpopulations with either the classical or the novel indices of LV dysfunction. CONCLUSION The results of our study suggest that alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in CKD patients without established CVD. The significance of the implication of the cellular arm of the immune system in the pathophysiological pathways of specific CVD phenotypes in CKD and the utility of immune cells subsets as tools to identify CKD patients who are at the highest risk for developing complications shall be elucidated by future research.

A study of left ventricular diastolic dysfunction in patients of sickle cell disease

Background: Left ventricular diastolic filling patterns are altered in patients with sickle cell anaemia and these diastolic abnormalities may be present in the absence of heart failure. These abnormal patterns suggest an intrinsic myocardial abnormality in patients with sickle cell anaemia and may prove to be early markers of cardiac disease. The ventricles do not properly relax and become stiff meaning they cannot fill with blood properly.Methods: This study was carried out in tertiary health care hospital in western India, where homozygous sickle cell disease patients and age and haemoglobin matched controls were taken into cross sectional observational study design.Results: The mean values of E, A, E/A, IVRT, DT, AT, were in normal range in controls. In cases although the mean values of E, A, E/A, IVRT, DT, AT were in normal range, there were 19 cases of sickle cell anaemia who had significant alteration in indices of diastolic LV function from normal range. Out of these 20 cases with diastolic dysfunction, 11 cases had significant increase in (E) velocity from normal range with E/A ratio more than 2 suggestive of restrictive filling pattern of diastolic dysfunction while in 8 cases E value was less than normal with increase in (A) velocity and E/A ratio was less than 1 suggestive of impaired relaxation pattern of diastolic dysfunction. When indices of diastolic LV function were compared in cases and controls, mean early peak filling velocity (E) was significantly higher in cases. Conclusions: In present study, out of 37 cases 19 (51%) cases had LV diastolic dysfunction. Of these 19 cases with diastolic dysfunction, 11 cases had restrictive filling pattern and 8 cases had impaired relaxation pattern of diastolic dysfunction.

Hemodialysis: effects of preload reduction on novel echocardiographic parameters of left ventricular function

Abstract Funding Acknowledgements Type of funding sources: None. Background Echocardiography has been widely used to study cardiac function in patients with end-stage renal disease on hemodialysis (HD), but cardiac function assessment by measuring cardiac dimensions and their rate of change is load dependent, therefore it is influenced by volume depletion. Effects of acute volume reduction on left (LV) and right ventricular (RV) function are still not well understood. Some studies investigated myocardial mechanics after dialysis using speckle tracking echocardiography (STE) but their relative load-dependency makes STE indices unable to account for changes in pre- and afterload. Myocardial work (MW) incorporates both deformation and load into its analysis and is an emerging tool to study LV myocardial function. There are no data about the effects of hemodialysis on LV MW. Purpose This study aimed to evaluate acute changes of novel echocardiographic indices of both LV and RV function after a HD session. Methods Patients with end-stage renal disease undergoing HD were prospectively enrolled. A transthoracic echo, including STE calculation of LV global longitudinal strain (GLS) and free wall RV strain, was performed before and after hemodialysis. Parameters of MW such as global work index (GWI), global constructive work (GCW), global work efficiency (GWE) and global wasted work (GWW) were quantified using a commercially available software package. Results 27 patients were enrolled, mean baseline parameters were: LV end-diastolic volume 136 ± 38 mL, LV ejection fraction (LVEF) 56.9 ± 7.5%, LV GLS -17.1 ± 4.1%, RV free wall strain -26.9 ± 5.6%, GWI 2117 ± 602 mmHg%, GCW 2299 ± 633 mmHg%, GWW 137 ± 88 mmHg, GWE 93 ± 3.6%, systolic arterial pressure 145 ± 26 mmHg and diastolic pressure 80 ± 16mmHg. After hemodialysis we observed a significative reduction in LV GLS (p = 0.04), RV strain (p = 0.002), GWI (p = 0.002, Figure I) and GCW (p = 0.004). No significative changes in LVEF and blood pressure were observed. Comparing patients using a LVEF cut-off of 55% (19 patients with LVEF≥55%, 8 patients &amp;lt;55%) we observed a significative reduction of LV GLS (p = 0.004), GWI (p &amp;lt; 0.001), GCW (p &amp;lt; 0.001) only in patients with LVEF ≥55% while RV strain and LV volume showed a reduction in both groups. We observed no significative differences in extracted volumes between the groups (2.6 vs 2.1 liters,p = 0.3). Patients with normal LVEF showed a significative negative variation (D) of LVEF (-1 vs 3%), GWI (-551 vs 38 mmHg%) and GCW (-522 vs 11 mmHg%). Correlations were found between DGWI and extracted volume (r= 0.46, p = 0.01), basal GWI and both DLVEF (r= 0.39, p = 0.04) and DLV GLS (r= 0,42, p = 0.02), basal LV GLS and DLVEF (r= 0.5, p &amp;lt; 0.01). Conclusions Our preliminary data show that, immediately after the HD session, there is a reduction in biventricular STE-derived systolic parameters. Patients with normal LV systolic function are more sensitive to acute volume changes and entity of volume depletion seems to be correlated with MW reduction. Abstract Figure.

Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs

BackgroundCardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min− 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min− 1 under various inotropic states.MethodsWe retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min− 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax).ResultsCPO showed the best correlation with LV SW min− 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min− 1 (LVPmaxr2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min− 1 (r2 = 0.28).ConclusionCPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU.

Higher plasma leptin levels are associated with reduced left ventricular mass and left ventricular diastolic stiffness in black women: insights from the Genetic Epidemiology Network of Arteriopathy (GENOA) study.

Our previous experimental animal data suggest a beneficial effect of leptin on LV structure and function. We hypothesized that leptin levels are associated with lower LV mass and myocardial stiffness which are important risk factors for the development of heart failure with preserved ejection fraction (HFpEF). We evaluated 1172 blacks, in which the prevalence of HFpEF is quite high, with preserved LV ejection fraction (EF > 50%) from the Genetic Epidemiology Network of Arteriopathy Study (mean age 62.9 years, 72% women), a community-based study to identify genes influencing blood pressure and target organ damage due to hypertension. Associations between leptin levels and indices of LV structure and function were evaluated using generalized estimating equations accounting for clustering in siblings. LV myocardial stiffness was evaluated using diastolic wall strain (DWS) measured by echocardiography. Analyses were stratified by sex because leptin levels were three times higher in women than men (p < 0.001). After adjustment for confounders, higher leptin levels were associated with lower LV mass (coefficient for 1 s.d. increase of leptin level: -5.825 g, 95% CI: -9.755 to -1.895 g, P = 0.004) and higher DWS (lower LV stiffness) (coefficient for 1 s.d. increase of leptin level: 0.009, 95% CI: 0.002-0.015, P = 0.007) in women. There were no statistically significant associations in men. In women, there were interactions between leptin levels and body mass index quartiles on LV mass and stiffness (p < 0.05 for both). Higher leptin levels were associated with lower LV mass and stiffness in obese but not lean black women.

Role of cardiac TBX20 in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM.

Three-dimensional speckle-tracking echocardiography derived parameters as a predictor of adverse events in patients with ESRD: validation of three-dimensional speckle-tracking echocardiography

Objectives: 3D speckle tracking echocardiography (3D-STE) was sensitive enough to distinguish diastolic dysfunction from normal function and predict cardiovascular events in idiopathic dilated cardiomyopathy. The purpose of this study was to investigate the validation of 3D-STE to predict clinical adverse events in peritoneal dialysis patients. Methods: A total of 108 patients with chronic kidney disease on maintenance home peritoneal dialysis were recruited (72 men, mean age 61.3±13.3 years). Both conventional and 3D-STE echocardiography were used to measure LV volume, deformation, diastolic function. New indices of diastolic LV function were calculated: filling duration at 25, 50% of LV volume which were expressed in percentage of diastolic duration (divided by the total filling duration). Dialysis adequacy and residual renal function were also measured. Results: Diastolic dysfunction had increased in LVFD25%/LVFD50% compared to normal diastolic function and the rate of filling progressively decreased with severity of DD, except pseudonormal diastolic dysfunction, which decreased below abnormal relaxation. Decreased LVFD25% ratio (cutoff =0.28) and LV end systolic volume assessed by 3D-TSE were independent predictor of primary endpoint events. Moreover,conventional diastolic function parameters evaluated by 2D Echo such as LV diastolic filling pattern, LVE/E', EDT, E/A were not predictors of primary end-point events in this study. ![Figure][1] Figure 1. Kaplan-Meier analysis Conclusion: Assessment of LVFD25% and end systolic volume using 3D-TSE has the potential to predict primary endpoint events in patients with peritoneal dialysis and may thus have clinical implications for management of such patients. [1]: pending:yes

103 INTER-STUDY REPRODUCIBILITY OF STRAIN MEASURMENTS BY CARDIAC MRI: A COMPARISON OF FEATURE TRACKING, SINGLE BREATH-HOLD TAGGING AND MULTI BREATH-HOLD TAGGING

<h3>Introduction</h3> Strain and strain rate are important indices of LV function and are of prognostic value in many cardiac conditions. The current gold standard for its measurement is myocardial tissue tagging using cardiac MRI (CMR) that requires acquisition of additional sequences and semi-automatic post-processing. Feature tracking (FT), a technique that relies on automatic tracking of voxels of tissue at the cavity-tissue interface throughout the cardiac cycle, has recently been introduced and shown to have reasonable inter-study reproducibility (Cofficient of variation (CoV) ∼20%) in healthy volunteers. The inter-study reproducibility of FT has not been reported in any patient groups nor compared to MRI tagging. We sought to compare circumferential strain and strain rate values using Tagging and FT, and determine their inter-study reproducibility in patients with severe Aortic Stenosis (AS). <h3>Methods</h3> CMR was performed twice on eight patients with isolated severe AS without obstructive coronary disease, on a 1.5 T (Siemens Avanto) scanner (median interval 12 days). Complementary tagged (CSPAMM) images were acquired with both single breath-hold (SBH: temporal resolution 42 ms) and multiple breath-hold (MBH: high temporal resolution 17 ms) sequences. InTag post-processing toolbox (Creatis, Lyon, France) in OsiriX (Geneva, Switzerland) was used to calculate the Circumferential Peak Systolic Strain (PSS), Peak Systolic Strain Rate (PSSR) and Peak Early Diastolic Strain Rate (PEDSR). Diogenes CMR FT software (TomTec Imaging Systems, Munich, Germany) was used to calculate the same parameters on the short-axis stack of SSFP cine images at basal, mid and apical levels, using an average of epicaridal and endocardial contours. <h3>Results</h3> PSS, PSSR and PEDSR were calculated globally (average of base, mid, apex) as well as individually for each slice. FT revealed overall higher values for global measurements than with both tagging techniques (p&lt;0.05 for SBH/MBH values vs FT) (table&nbsp;1). However, excluding the apical slice, there was no difference between the PSS and PEDSR between the Tagging techniques and FT. The inter-study reproducibility results are shown in Table&nbsp;2. Results were comparable between Tagging and FT. The apical slice was found to be the least reproducible (CoV 20.38%, 19.69%, 16.77% for SBH, MBH and FT respectively). Excluding the apical slice improves the reproducibility of both tagging and FT. <h3>Conclusions</h3> This study has demonstrated that Global PSS, PSSR and PEDSR values are considerably higher with FT than Tagging in patients with severe AS unless the apical slice is excluded. The reproducibility of strain and strain rate measurements with FT are comparable to that of tagging in severe AS patients. Given that FT does not require additional image acquisitions to standard cine images this technique is likely to become the preferred method for strain and strain rate quantification with MRI.

LEFT VENTRICULAR MASS, PUMP PERFORMANCE AND CARDIOVASCULAR EVENTS: THE STRONG HEART STUDY: PP.22.374

Background: Ejection-phase indices of LV function such as ejection fraction (EF) are strong prognostic indicators. However, at given level of EF, LV pump performance (stroke volume [SV]) may differ, depending on LV size. but, it is unknown whether low SV is a prognostic marker independent of its strong biological collinearity with high LV mass (LVM). We assessed the associations of EF, SV and LVM with cardiovascular (CV) events in a large population free of CV disease. Method: After the 2nd SHS exam, we examined 8-year outcome of quintiles of EF, SV (z-derived method) and LVM in 2323 participants (58 ± 7 yrs; 62% women) without prevalent coronary heart disease, stroke or heart failure (hypertension in 39%, diabetes in 45% and obesity in 54%). Results: In univariate Cox models, risk of composite fatal or non-fatal cardiovascular (CV) events increased across lower quintiles of EF (log rank = 21.7; p = 0.0002) and higher quintiles of LVM (log rank = 40.8; p < 0.00001). In contrast SV did not show significant predictive value. LVM was negatively related to EF (r = −0.37), but was positively correlated with SV (r = 0.66), (both p < 0.0001). Thus, the level of LVM, could confound evaluation of the association of SV with subsequent CV events. Thus, we evaluated LV pump performance per gram of LVM (SV/LVM). Kaplan Meier curves revealed a progressively higher rate of CV events with lower quintiles of SV/LVM (log Rank = 36.3; p < 0.0001). Cox regression, adjusting for age and sex and including EF, SV and LVM showed that hazard of incident CV events increased with higher LVM (HR = 1.1/10 g, CI = 1.05–1. 12, p < 0.0001) and lower SV (HR = 0.90/10 mL, CI = 0.80–0.98; p < 0.01), with no independent effect of EF (HR = 0.90/10%, CI = 0.70–1.03, p = 0.11). Conclusion: Evaluation of LV pump performance is influenced by the amount of myocardial muscle pumping blood into the arterial tree. When LV mass is taken into consideration, indices of LV pump performance may be at least as good as ejection-phase indices of LV function for identification of subjects at risk of incident CV events.

Abstract 4373: Effects of Darbepoetin-Alpha on Plasma Markers of Oxidative and Nitrosative Stress in Anemic Patients with Chronic Heart Failure

Increased oxidative and nitrosative stress may be important pathophysiologic mechanisms that mediate cardiac and vascular dysfunction in chronic heart failure (CHF). This study investigate the effects of recombinant human erythropoietin analogue darbepoetin-alpha(α) on plasma markers of oxidative and nitrosative stress along with cardiac function and exercise capacity in patients with CHF and anemia. Thirty CHF patients [Hew York Heart Association class, II-III; LV ejection fraction (EF) &lt;40%; hemoglobin &lt;12.5 g/dl; serum creatinine &lt;2.5 mg/dl] were randomized (1:1) to receive either a 3-month darbepoetin-α regimen at 1.5 μg/Kg every 20 days plus oral iron or placebo plus oral iron. Echocardiographic indices of LV function, plasma B-type natriuretic peptide (BNP) and plasma markers of oxidative [oxidative: malondyaldheyde (MDA), carbonyl proteins; anti-oxidative: glutathione) and nitrosative (nitrotyrosine) stress, and 6-min walked distance were assessed at baseline and post-treatment. A significant improvement of LV ejection fraction (p&lt;0.01) and six min walked distance (p&lt;0.001) was observed only in darbepoetin-treated patients. Moreover, plasma BNP (661±858 from 1102±1200 pg/ml, p&lt;0.001), MDA (2.1±0.9 from 2.5±0.8 ng/ml, p&lt;0.01), protein carbonyl (1.7±0.6 from 2.1±0.7 ng/ml, p&lt;0.01) were significantly reduced, while plasma anti-oxidative enzyme glutathione (124±11 from 116±10 ng/ml, p&lt;0.05) was increased after darbepoetin treatment. These factors remained unaffected in placebo-treated patients. Darbepoetin-induced percent changes in carbonyl protein was significantly correlated with respective changes in BNP (r=0.55, p&lt;0.05) and LV ejection fraction (r=−0.46, p&lt;0.05). Finally, a drug-induced percent reduction in nitrotyrosine was significantly correlated with the respective improvement in 6 min walked distance (r=−0.63 p&lt;0.05). Darbepoetin seems to attenuate deleterious effects of oxidative and nitrosative stress into cardiovascular system of anemic patients with CHF. This beneficial action may be related with the drug-induced improvement of cardiac function and exercise capacity of these patients.

Impact of Cardiac Rehabilitation on the Clinical Course of Coronary Artery Disease: Lessons Learned

Cardiac rehabilitation (CR) has been shown to be effective in secondary prevention of coronary artery disease (CAD), with the potential to stabilize the course of atherosclerosis. Recent studies suggest that exercise training may have beneficial effects on contractile dysfunction caused by ischemia and reperfusion. CR is currently under-utilized in the USA. We studied our CR Registry of 3,509 patients, to evaluate the effects of a physician-directed CR exercise program in CAD patients. Clinical indications included CABG, valve surgery, percutaneous coronary intervention (PCI), chronic stable angina and CHF. From 1/98 to 12/06, 3,509 patients (mean age 69; 36% female) were enrolled in the supervised CR program. We used a preset exercise protocol of ECG-monitored, symptom-limited bicycle ergometry and treadmill, up to 60 minutes per session, 3 days a week for 12 weeks. The program was tailored to meet patient-specific needs, including nutrition counseling and risk factor modification. Multiple indices of exercise tolerance, LV function and metabolic parameters were recorded at entry and completion of (Phase II) CR. Results:See Table. In this series, 0.7% had MI, 10.6% had a repeat revascularization and 0.7% died. Conclusions: (1) In patients with CAD, a supervised CR program significantly improves multiple indices of functional capacity. (2) This is paralleled by significant improvement in global LV systolic and diastolic performance, indices that are known to impact long-term cardiac morbidity and mortality. (3) Our data demonstrates that CR can positively impact the course of CAD and should be more widely prescribed.Tabled 1ResultsVariablePre-RehabPost-Rehab’P’ValueMean NYHA Class2.61.30.003∗∗Workload on TM (METs)3.2 ± 1.85.2 ± 1.80.022∗∗Cycle Ergometry Time (min)8.5 ± 2.220.7 ± 2.80.001∗Systolic BP (mmHg)150.6 ± 14.7138.9 ± 15.70.000∗Mean LVEF (%)32.5 ± 6.439.4 ± 10.60.002∗∗Diastolic dysfx. (%)42.216.50.004∗∗Smoking (%)161.60.002∗∗HDL/Chol Ratio4.63.50.036∗∗∗ :‘P’ value significant at < 0.0001; ∗∗ : ‘P’ value significant at < 0.05. Open table in a new tab ∗ :‘P’ value significant at < 0.0001; ∗∗ : ‘P’ value significant at < 0.05.

Doppler echocardiographic assessment of left atrial appendage flow velocities in normal cats

Objectives The use of transthoracic Doppler echocardiography (TTDE) to evaluate the patterns and technique of measuring of left atrial appendage (LAA) flow velocities in normal cats. Background Left atrial enlargement and dysfunction are characteristic features of feline cardiomyopathy that may cause blood stasis in the left atrium (LA). This low flow state may be associated with hypercoagulability and thrombus formation. Left atrial enlargement, spontaneous echocardiographic contrast, and decreased velocity of LAA flow may be early indicators of thromboembolic risk. Little is known about the patterns and determination of LAA flow in normal cats. Animals, materials and methods Transthoracic Doppler echocardiography was used to evaluate LAA flow in 47 normal cats and to assess the effects of age, body weight, sex, heart rate, arterial blood pressure, and echocardiographic indices of LA and LV size and function on LAA flow variables. Results Adequate LAA flow signals could be recorded in 43 (92%) cats. Polyphasic LAA flow profiles were obtained in all cats, consisting of two (79%), three (16%), or four (5%) flow waves. Maximum LAA flow velocity (mean ± SD) was 0.47 ± 0.20 m/s (range 0.24–1.00) and average LAA flow velocity was 0.42 ± 0.17 m/s (0.22–0.93). There was a weak correlation between LAA flow velocity and LA size based on maximum LA diameter ( r = 0.36, p = 0.018) and maximum LA area ( r = 0.44, p = 0.004). There was no association between LAA flow velocity and any other independent variable evaluated. Conclusion LAA flow may be recorded by use of TTDE in cats. The results of this study can be used for comparison with LAA flow patterns found in disease states.

70 Differential proteomic profiling and hemodynamic characterization of the pressure overloaded right ventricule in young rats: a novel approach

disease. We sought to determine the mechanisms underlying the progression from compensated RV hypertrophy to failure using an alternative approach. Therefore, we studied alterations in myocardial protein expression in relation to RV function. Here, we report the results after 6 weeks of RV pressure overload. Methods: Male Wistar rats (age 8.1=t=0.4 wk) underwent Pulmonary Artery Banding (PAB) (n=6) or sham (n=6) operation. Load(in)dependent RV and LV function was characterized in vivo by means of the end-systolic pressure-volume relation (ESPVR) using the conductance catheter technique. Myocardial cytoplasmatic protein expression was determined by proteomic analysis of individual homogenates of RV myocardium (6 gels per group ie. sham and PAB). Results: In PAB animals the ratio of RV and RA to body weight was increased (0.58±0.02 vs. 1.034-0.05 RV, p<0.001 and 0.13±0.01 vs. 0.21-4-0.03 RA rag/g, p<0.05). Hemodynmnics: Hypertrophic RV endsystolic and end-diastolic pressures were increased (31-t-1 vs. 65±5 and 4.34-0.5 vs. 10.54-1.l mmHg, p<0.001). After PAB cardiac output decreased significantly, but heart rate was unchanged. Load-dependent indices of RV systolic performance (dPdtMax and stroke work) increased significantly (p<0.001) as a result of PAB, as well as the loadindependent slope of the ESPVR (0.09±0.03 vs. 0.29±0.02 mmHg/bL, p<0.001). In contrast, indices of LV function were not affected. Proteomics: Several stress-and metabolic proteins significantly differing in intensity were identified. A general downregulation was observed in betaoxidation pathway proteins. Glycolytic pathway proteins showed an increased expression. Three spots were identified as HSP27 (+1.7-3.5 (in PAB), p<0.05), suggesting HSP27 modifications. Contusions: Our results indicate that 6 weeks of PAB leads to compensated RV hypertrophy in rats. Despite the enhanced RV contractile state, cardiac output falls, suggesting initial transition from compensated state to failure. In these conditions, specific alterations and modifications in metabolic and stress related protein expressions were present in the hypertrophic RV. We expect that alterations in myocardial protein expression (in eytoplasmatic and other subfractions) associated with the progression to RV failure will be disclosed in further studies.

Noninvasive Estimation of Left Ventricular Diastolic Filling Pressure From Doppler Tei Index

Background. Discrepancies between LV function and its filling pressure are typically characterized with severe dysfunction and normal filling pressure, suggesting reduced preload. Reduced preload can cause lower early to late diastolic mitral flow velocity ratio (E/A) on the Doppler echocardiogram. Therefore, we hypothesized that the relation between LV function and filling pressure is poorer in patients with mitral flow E/A < 1.0, however, the same relation is better in those with E/A ≥1.0.Objectives. The present study sought to investigate and compare the relation between LV filling pressure and indices of LV function, including the recently proposed Doppler Tei index, between patients with mitral flow E/A < 1.0 and those with the E/A ≥ 1.0.Methods. LV end-diastolic and mid-diastolic (before atrial contraction: pre-A) pressures were directly measured by catheterization in 74 consecutive patients with normal sinus rhythm. Tei index was measured from pulsed Doppler LV inflow and outflow velocity recordings, as the sum of isovolumetric contraction and relaxation time divided by LV ejection time. Indices of cardiac function including LV end-diastolic and end-systolic volumes, LV ejection fraction, left atrial dimension, mitral flow E/A, deceleration time of E velocity, and its slope were also measured by Doppler echocardiography.Results. In all subjects, there were no significant or relatively weak correlations between the LV filling pressures and indices of LV function (r2 = 0.05 ∼ 0.27, N.S. ∼ p < 0.0001). In patients with E/A < 1.0, the correlations were not significant for all indices of LV function. However, multiple indices of LV function, especially the Tei index, showed significant and better correlations with both LV end-diastolic and pre-A pressures (r2 = 0.66 and 0.63, p < 0.0001, respectively).Conclusions. Correlations between LV filling pressure and indices of LV function are worse and not significant in patients with mitral flow E/A < 1.0, however, the correlations are better and significant in patients with the E/A ≥ 1.0. Indices of LV function, especially Tei index, allows noninvasive estimation of LV diastolic filling pressure in patients with mitral E/A ≥ 1.0.

How Should We Assess Diastolic Function in Hypertension?

Objective: the aim of our study was to assess the relative merits of three indices of diastolic LV function in a group of patients with hypertension and normal systolic function and a group of healthy controls. Design: In this echocardiographic study, diastolic LV function was assessed by E/A ratio using pulsed Doppler recording and by atrial to total mitral annulus motion (AC) and maximal longitudinal LV relaxation velocity (RVm) by M-mode recordings from apical views. The study took place in the Department of Clinical Physiology in a secondary referral centre. Nineteen consecutive patients with uncomplicated hypertension referred to echocardiographic examination and 20 age- and sex-matched controls were included in the study. Results: All three measures of diastolic function, E/A ratio, AC and RVm indicated impaired diastolic function in the hypertensive group, compared to the healthy controls. However, E/A ratio and AC showed a considerable overlap between the groups, whereas there was a highly significant difference in RVm between the hypertensive group and the controls, with much less of an overlap. Conclusion: The results indicate that of these three indices of diastolic function, RVm may be the most appropriate in patients with hypertension and normal systolic LV function.

941-22 Role of Dynamic Changes in Left Ventricular Function in Determining Exercise Capacity in Patients with Nonobstructive Hypertrophic Cardiomyopathy

Measurements of LV morphology and function at rest predict weakly exercise capacity in hypertrophic cardiomyopathy (HC). Aim of this study was to verify whether dynamic changes in LV function relate to exercise duration in HC. Accordingly, we studied 25 patients, off-drugs, with nonobstructive HC (15 males, aged 43 ± 13 yrs). who undervvent baseline Doppler echocardiography, cardiac catheterization, and symptom-limited supine bicycle exercise (25 watt/2 mins) with postexercise Doppler echocardiography. Exercise capacity ranged from 50 to 125 (mean: 79 ± 27) watts. No relation was found between exercise time and indices of LV morphology (i.e. maximal wall thickness, wall thickness index, end-diastolic and end-systolic dimensions). or function at rest (i.e. LV ejection fraction, stroke volume index, right- and left-sided intracavitary pressures, Doppler indices of LV diastolic filling). In contrast, exercise capacity correlated significantly (p &lt; 0.01) with the magnitude of changes recorded at peak exercise in ejection fraction (r = 0.65). LV end-diastolic volume (r = 0.67), and Doppler peak early filling velocity (r = 0.60). Change in ejection fraction related significantly (p &lt; 0.01) to change from baseline in both LV end-diastolic volume (r = 0.71) and peak early filling velocity(r = 0.55). Multiple regression analysis revealed that the response of ejection fraction to exercise was the strongest predictor of exercise capacity (p = 0.001). Noteworthy, 10/25 patients exhibited the lack of stress-induced increase in ejection fraction. We conclude that in nonobstructive HC: (1) dynamic changes in LV function correlate with exercise duration; (2) indices of LV morphology and function at rest do not predict exercise capacity; (3) exercise intolerance seems to be caused by worsening in diastolic filling, leading to the inability to increase LV volume with exercise to maintain systolic function.

Assessment of left ventricular function after sublingual administration of nifedipine in patients with moderate to severe hypertension

To evaluate the left ventricular functional changes induced by acute decreases in blood pressure in 15 patients with systemic hypertension and left ventricular hypertrophy, this study used Doppler and M-mode echocardiographic derived left ventricular indices. After 30 minutes of administration of sublingual nifedipine, both systolic and diastolic blood pressure decreased and heart rates increased. The left ventricular end-systolic dimension decreased but not the end-diastolic dimension, which suggests that sublingual nifedipine may decrease only afterload, not preload. Total peripheral resistance decreased from 2770 to 1960 dyne.sec.cm-5. The M-mode-derived peak rate of dimension changes improved both the systolic and diastolic phase, and Doppler-derived indices of atrial contribution to ventricular filling decreased. Because both the systolic and diastolic phase indices of LV function are sensitive to variations in both preload and afterload, the improvement of myocardial contractility per se cannot necessarily be attributed to the direct effect of the drug to myocardium. Though favorable effects on the myocardial oxygen supply-demand ratio or increased adrenergic tone stimulated by the decline in systemic arterial pressures may contribute to the augmentation of LV systolic and diastolic function observed after nifedipine in the present study, the apparent augmentation of LV function appears to be attributable primarily to afterload reduction.