Wide Range Of Ejection Fractions Research Articles

Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction.

The development of new drugs and device therapies has led to remarkable advancements in heart failure (HF) treatment in the past couple of decades. However, it becomes increasingly evident that guideline-directed medical therapy cannot be one-size-fits-all across a wide range of ejection fractions (EFs) and various aetiologies. Therefore, classifications solely relying on EF and natriuretic peptide make optimization of treatment challenging, and there is a growing exploration of new indicators that enable efficient risk stratification of HF patients. Particularly when considering HF as a multi-organ interaction syndrome, the cardiorenal interaction plays a central role in its pathophysiology, and albuminuria has gained great prominence as its biomarker, independent from glomerular filtration rate. Albuminuria has been shown to exhibit a linear correlation with cardiovascular disease and HF prognosis in multiple epidemiological studies, ranging from normal (<30mg/g) to high levels (>300mg/g). However, on the other hand, it is only recently that the details of the pathological mechanisms that give rise to albuminuria have begun to be elucidated, including the efficient compaction/tightening of the glomerular basement membrane by podocytes and mesangial cells. Interestingly, renal disease, diabetes, and HF damage these components associated with albuminuria, and experimental models have demonstrated that recently developed HF drugs reduce albuminuria by ameliorating these pathological phenotypes. In this review, facing the rapid expansion of horizons in HF treatment, we aim to clarify the current understanding of the pathophysiology of albuminuria and explore the comprehensive understanding of albuminuria by examining the clinically established evidence to date, the pathophysiological mechanisms leading to its occurrence, and the outcomes of clinical studies utilizing various drug classes committed to specific pathological mechanisms to put albuminuria as a novel axis to depict the pathophysiology of HF.

CA-125 concentrations are associated with renal function decline but not congestion or prognosis in patients with chronic heart failure: results from EMPEROR-POOLED

Abstract Background Carbohydrate antigen 125 (CA-125, also described as cancer antigen 125), has emerged as a candidate biomarker of congestion in heart failure (HF). Effects of sodium/glucose cotransporter-2 inhibitor therapy on CA-125 and its role as a prognostic measure in HF remains uncertain. Purpose In study participants from the EMPEROR-Preserved and EMPEROR-Reduced trials, across a wide spectrum of ejection fraction (EF) and renal function, we sought to investigate associations between CA-125 and congestion, the effect of empagliflozin on CA-125 concentrations, and the ability of the biomarker to predict cardio-renal outcomes. Methods 1111 patients with HF and available biomarker data were included into this analysis. Serum CA-125 was measured at baseline, 12 and 52 weeks using an Electroluminescence assay. The measurements were performed within a biomarker research agreement of Boehringer Ingelheim, the sponsor of these trials and Roche Diagnostics International Ltd. Congestion signs or symptoms were evaluated across CA-125 tertiles. A mixed model for repeated measurements was used to compare the treatment effects on CA-125. Multivariable analyses adjusted for the prespecified EMPEROR baseline variables plus N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were used to examine the association of CA-125 with HF hospitalization or cardiovascular (CV) death and estimated glomerular filtration rate (eGFR) slope. Results Across CA-125 tertiles at baseline, no significant association was present with HF symptom severity, jugular vein distention, pulmonary rales, S3 gallop or peripheral oedema (all p-values &amp;gt;0.10). Treatment with empagliflozin was associated with 7% greater reduction of CA-125 level versus placebo to week 12 (adjusted geometric mean ratio: 0.93; 95% confidence interval [CI], 0.87-0.99, p = 0.03) but not to week 52 (adjusted geometric mean ratio: 0.97, 95% CI 0.90-1.06; p = 0.50). No significant association was found for tertiles of CA-125 at baseline with the risk of CV death/HF hospitalization; with a hazard ratio (HR) for higher vs lower CA-125 tertiles of 1.34 (95% CI 0.91–1.96). In the same model NT-proBNP and hs-cTnT were strongly prognostic (both p-values &amp;lt;0.0001). Compared to lower tertiles, study participants in the third CA-125 tertile had higher rate of kidney function decline with a more negative eGFR slope (p for trend = 0.03). Conclusion In chronic HF, across a wide range of EF and of renal function, CA-125 levels were not strongly associated with clinical signs or symptoms of congestion. Empagliflozin lowered CA-125 levels more than placebo at week 12 but not at week 52. Among individuals with HF, CA-125 concentrations did not provide additional prognostic information for CV death/HF hospitalization beyond conventional cardiac biomarkers but may predict subsequent kidney function decline.

Feasibility and accuracy of artificial intelligence for automatic qualification of two-dimensional and three-dimensional left ventricular ejection fraction and global longitudinal strain in echocardiography

To investigate if fully automated measurements of two-dimensional (2D) and three dimensional (3D) echocardiographic left ventricular ejection fraction (EF) and 2D global longitudinal strain (GLS) using a novel technology based on machine learning, deep learning and artificial intelligence (AI) are feasible and comparable with a conventional application by echocardiography cardiologists. Methods: From 12/2020 to 12/2021, 208 patients with heart disease with a wide range of EF were enrolled in the study in Vietnam National Heart Institute, Bach Mai hospital. Three standard apical cine-loops were analyzed using the AI model. The AI automated method measured 2D EF, 3D EF and GLS and was compared with conventional methods performed by echocardiography cardiologists. Results: The AI method succeeded to both correctly classify all three standard apical views in 95% of patients (four-chamber view: 94,2%; two-champer view:94,7% và three-chamber view: 95,2%.) and perform precise timing of cardiac events. There were strong correlations between 2D/3D EF measured by AI and the 2D/3D EF measured by echocardiography cardiologists (r = 0,78, p&lt;0,001 and r = 0,65, p&lt;0,001, respectively). There was a strong correlation between GLS measured by AI and the GLS measured by echocardiography cardiologists on speckle tracking echocardiography (r = 0,71, p&lt; 0,001). Conclusion: Fully automated measurements of 2D/3D left ventricular ejection fraction and global longitudinal strain using a novel machine learning, deep learning AI-based technology are feasible and fast and they yield results comparable with conventional methods performed by echocardiography cardiologists.

Sodium-glucose co-transporter 2 inhibitors for the treatment of cardio-renal syndrome.

The 2021 guidelines of the European Society of Cardiology on the diagnosis and therapy of heart failure (HF) introduced relevant changes in the pharmacological treatment of chronic HF. Among these, certainly the most significant was the introduction in the therapeutic flow-chart (with the highest recommendation level) of the sodium glucose co-transporter 2 (SGLT2) inhibitors. In fact, SGLT2 inhibitors are responsible for major paradigm shifts in the care of patients with or at high risk for HF, progression of chronic kidney disease, or both. SGLT2 inhibition demonstrated to improve cardiovascular outcomes in patients with HF over a wide range of ejection fractions, regardless of diabetic status, and have a strong nephroprotective effect. There are several important interactions between heart disease and kidneys disease. Indeed, acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. The term 'cardiorenal syndrome' has been applied to these interactions. Since kidneys dysfunction in the setting of HF has a strong prognostic relevance, drugs that can slow down the decline of renal function are of utmost importance. Here, we discuss about the beneficial effects of SGLT2 inhibitors on the kidneys function in patients with HF and how these effects can improve both renal and cardiovascular outcomes.

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure

Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied. To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels. This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022. Randomization to empagliflozin or placebo. New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria. A total of 9673 patients were included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300 mg/g). Compared with normoalbuminuria, macroalbuminuria was associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in events was observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality or HF hospitalization was consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend = .71). Treatment with empagliflozin was associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P = .005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P = .009) but not with a reduction in UACR in the overall population; however, UACR was reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P = .008). In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria. ClinicalTrials.gov Identifiers: NCT03057977 and NCT03057951.

Abstract 34: 12-month Clinical Outcomes Among Patients With Heart Failure And Reduced To Preserved Ejection Fraction Based On Sacubitril/valsartan Versus Angiotensin Converting Enzyme Inhibitor Or Angiotensin Receptor Blocker Use - A Retrospective, Parallel, Multi-group Study

Introduction: Real-world 12-month outcomes of sacubitril/valsartan (sac/val) vs. ACEi or ARB use among patients with HFrEF (EF &lt; 40%) through HFpEF (HFmrEF EF 40-49% and HFpEF EF 50-60%) are not well known. A better understanding of hospitalization (hosp), emergency department (ED) visits and mortality provides new information about medication benefits in patients with HF and a wide range of ejection fractions (EF). Methods: Data were retrieved from a multi-state healthcare system database. Patients prescribed sac/val from Aug. 1 2015-Jul. 31 2018 were matched to those on ACEi or ARB based on age, sex, EF, comorbidity status, hospital vs. ambulatory index date reflecting medication use and systolic blood pressure. Twelve-month outcomes based on sac/val vs. ACEi or ARB were assessed using linear, logistic, and Poisson models with generalized estimating equations. Results: Of 3588 patients (1794 per group), mean (SD) age was 64.2 (13.0) years, 70.3% were male, 20.7% were Black, and mean systolic blood pressure was 122.1 (16.1) mmHg. By HF factors, 47.6% were NYHA-FC II and mean EF% was 29.0 (9.9); 349 (9.7%) had HFmrEF or HFpEF. At baseline, 92.4% were on beta-blockers, 43% were on aldosterone antagonists and 63.1% were on loop diuretics. Over 12 months, 125 patients died (38 sac/val vs. 87 ACEi or ARB; p &lt;0.001). Sac/val use was associated with fewer 12-month all-cause and HF hosp, HF ED visits and the composite outcome (all p &lt;0.001); see Figure of adjusted event rate (%) odds ratios. Conclusions: Among patients with HFrEF, HFmrEF and HFpEF (EF up to 60%), use of sac/val was associated with fewer 12-month death and morbidity (all-cause and HF hosp and HF-related ED visits). Patient and provider factors that facilitated sac/val use and improved clinical outcomes should be studied.

Empagliflozin and Serum Potassium in Heart Failure: An Analysis From EMPEROR-Pooled

Dyskalaemia is associated with poor prognosis in heart failure (HF). Hyperkalaemia often leads to interruption and discontinuation of neurohormonal antagonists, potentially aggravating prognosis. Sodium-glucose co-transporter 2 inhibitors improve HF prognosis across a wide range of ejection fraction and may reduce hyperkalaemia, which may have important clinical implications. We studied prognostic associations of dyskalaemia and the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF.

Prognostic Value of NT-Pro Brain Natriuretic Peptide During Exercise Recovery in Ischemic Heart Failure of Reduced, Midrange, and Preserved Ejection Fraction.

Ischemic heart disease is a leading cause of heart failure (HF), which continues to carry a high mortality despite considerable improvements in diagnosis and treatment. N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) measured at rest is a recognized diagnostic and prognostic marker of HF of reduced ejection fraction (HFrEF); however, its value in patients with HF of midranged/preserved ejection fraction (HFmrEF/HFpEF) is not well established. We examined the prognostic value of NT-pro-BNP during recovery from exercise in patients with ischemic HF (IHF) of any ejection fraction. Patients (n = 213) with HF (123 HFrEF, 90 HFmrEF/HFpEF) underwent cardiopulmonary exercise testing. Doppler echocardiography was used to estimate resting pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE). NT-pro-BNP was determined at rest, peak exercise, and after 1 min of exercise recovery. Patients with HFrEF had higher plasma levels of NT-pro-BNP at rest, peak exercise, and recovery than those with HFmrEF/HFpEF (984 ± 865 vs 780 ± 805; 1012 ± 956 vs 845 ± 895; 990 ± 1013 vs 808 ± 884 pg/mL; P < .01, respectively), whereas ΔNT-pro-BNP peak/rest and ΔNT-pro-BNP recovery/peak were similar (60 ± 100 vs 50 ± 96; -25 ± 38 vs -20 ± 41 pg/mL, P > .05). During the tracking period (22.4 ± 20.3 mo), 34 patients died, 2 underwent cardiac transplantation, and 3 had left ventricular assist device implantation. In a multivariate regression model, only NT-pro-BNP during exercise recovery and TAPSE/PASP were retained in the regression for the prediction of adverse events (χ2 = 11.4, P <.001). NT-pro-BNP value during exercise recovery may be a robust predictor of adverse events in patients with IHF across a wide range of ejection fraction.

Determinants of Cardiorespiratory Fitness in Patients with Heart Failure Across a Wide Range of Ejection Fractions

Impaired cardiorespiratory fitness (CRF) in heart failure (HF) is influenced by a complex array of cardiac and extracardiac factors. The study aimed to identify clinical determinants of CRF measured as peak oxygen consumption (peak VO2) in HF patients, and to determine a peak VO2 prediction model using regression equations. Retrospective analysis of 200 HF patients who completed treadmill cardiopulmonary exercise testing and underwent Doppler echocardiography and/or biomarker analysis on the same day was performed. After univariate linear regression analysis, a multivariate peak VO2 prediction model was developed using significant variables in a stepwise linear regression analysis. In subjects with repeated testing, Pearson's correlation was used to assess correlations between measured and predicted change in peak VO2 (Δpeak VO2) over time. Mean age was 57 years, with 55% being male. Stepwise linear regression was used to generate a weighted model for peak VO2: 30.895 + (-0.112•age[years]) + (0.296•hemoglobin [g/dl]) + (-0.101•E/e'[unit change]) + (-0.202• body mass index [kg/m2]) + (-0.593• N-terminal pro-brain natriuretic peptide [logN pg/ml])) + (-1.349•CRP [log mg/L]). Predicted peak VO2 correlated strongly with measured peak VO2 in HF with reduced ejection fraction and HF with preserved ejection fraction patients (r = +0.63, p<0.001; r = +0.64, p<0.001, respectively). Predicted Δpeak VO2 correlated with measured Δpeak VO2 (r = +0.23, p<0.001). In conclusion, in patients with HF across a wide range of left ventricular ejection fraction, age, systemic inflammation, oxygen carrying capacity, obesity, and elevated filling pressures are the strongest predictors of impaired CRF. The proposed CRF model allows prediction of peak VO2 in HF patients and may be used to estimate peak VO2 changes over time.

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction.

Background: Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.Methods: Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log10) and NT-proBNP (logN).Results: Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5–9.0] mg/L, and NT-proBNP levels were 377 [106–1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16 ± 4 mlO2•kg−1•min−1. CRP levels significantly correlated with peakVO2 in all patients (R = −0.350, p < 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, N = 109) (R = −0.282, p < 0.001) and in those with preserved EF (HFpEF, N = 57) (R = −0.459, p < 0.001). NT-proBNP levels also significantly correlated with peak VO2 in all patients (R = −0.330, p < 0.001) and separately in patients with HFrEF (R = −0.342, p < 0.001) and HFpEF (R = −0.275, p = 0.032). CRP and NT-proBNP did not correlate with each other (R = 0.05, p = 0.426), but independently predicted peak VO2 (R = 0.421, p < 0.001 and p < 0.001, respectively).Conclusions: Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.

Quantification of circumferential, longitudinal, and radial global fractional shortening using steady‐state free precession cines: A comparison with tissue‐tracking strain and application in fabry disease

Conventional calculation of myocardial strain requires tissue-tracking. A surrogate for strain called global fractional shortening (GFS) is proposed based on changes in dimensions of endocardial and epicardial surfaces without tissue-tracking. Three-dimensional endocardial and epicardial left ventricular surfaces traced at end-diastole and end-systole using conventional steady-state free precession cine images were used to calculate GFScc (circumferential), GFSll (longitudinal), and GFSrr (radial) using fractional length changes in each direction over the heart surface. GFS values were validated using finite element models (FEM) and in vivo using tagging-derived strains (εcc ,εll ,εrr ) in patients with a wide range of ejection fraction (EF) and diagnosis (n=32). GFS was also measured in 31 patients with Fabry disease and matched healthy controls. GFS values were within 3% of average FEM-derived Lagrangian strains and had good agreement in vivo (GFScc =-14 ± 4%, εcc =-14 ± 4%, R(2) =0.85; GFSll =-12 ± 4%, εll =-12 ± 4%, R(2) =0.72; GFSrr =46 ± 21%). εrr could not be measured reliably from tagging. Compared with healthy controls with matched EF, patients with Fabry disease had significantly increased GFScc (Endo) (-28 ± 3% versus -25 ± 2%), decreased GFScc(Epi) (-10 ± 2% versus -11 ± 2%) and decreased GFSll for all components. GFS yields similar values to conventionally measured strains without requiring tissue-tracking. Compared with controls, patients with Fabry disease have significant differences in several GFS components.

Abstract 17352: Incidence and Predictors of Stroke in Patients with Chronic Heart Failure: Does Left Ventricular Function Matter? Insights From the CHARM Program

Objectives Patients with heart failure and reduced ejection fraction (HF-REF) are at increased risk of stroke, with some studies suggesting an inverse association between ejection fraction (EF) and stroke risk. The rate of stroke in simultaneously enrolled patients with HF-REF and preserved EF (HF-PEF) has not been reported and the predictors of stroke in a contemporary population of patients with HF are unknown. The Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity (CHARM) program, which included patients with a wide range of EF, provided a unique opportunity to examine these questions about stroke in HF. Methods We evaluated risk factors for stroke with multivariable Cox proportional hazard regression analysis using forward- and backward-stepwise selection of candidate variables, with gender, history of hypertension, EF and randomized treatment (i.e. candesartan) forced into the model. Results Of the 7599 participants in CHARM, 287 (3.8%) experienced a fatal or nonfatal stroke during a median follow-up of 37.7 months. The stroke rate was 1.3 (95% CI=1.1-1.5) and 1.4 (95% CI=1.2-1.7) per 100 pt yrs in subjects with reduced and preserved EF respectively. The 5 strongest predictors of stroke (ranked by chi-square value) were: older age, previous stroke, higher systolic blood pressure, diabetes and atrial fibrillation on baseline ECG; other independent predictors are shown in the figure. Univariate predictors not retained in the multivariable model were: history of hypertension, NYHA class III or IV, baseline oral anticoagulant use, previous coronary bypass surgery, current smoking, signs of HF, diuretic use and female sex; none of the other forced variables were predictive in either the univariate or multivariable models. Conclusions The rate of stroke is similar in patients with HF-REF and HF-PEF. Even in this relatively normotensive population, higher systolic BP was associated with greater stroke risk.

Validation of an echo-Doppler decision model to predict left ventricular filling pressure in patients with heart failure independently of ejection fraction

To test a decision model for non-invasive estimation of left ventricular filling pressure (LVFP) in patients with left ventricular (LV) dysfunction and a wide range of ejection fractions (EF). In patients with LV dysfunction (n = 270; EF = 42 +/- 16%), classification and regression tree (CART) analysis was used to generate a model for the prediction of elevated LVFP, defined as pulmonary capillary wedge pressure (PCWP) >15 mmHg, in a derivation cohort (n = 178). At each step of the decision tree, nodes including single or multiple criteria connected by Boolean operators were tested to achieve the best information entropy gain. Averaged mitral-to-myocardial early velocities ratio (E/e') > or =13 OR E-wave deceleration time <150 ms was closely associated with elevated LVFP. Alternatively, prediction of PCWP >15 mmHg needed the following criteria to be satisfied: (i) intermediate E/e' (13 > E/e' > 8); (ii) left atrial volume index >40 mL/m(2) OR ratio of mitral E-wave and colour M-mode propagation velocity >2 OR difference in duration of pulmonary vein and mitral flow at atrial contraction >30 ms; (iii) estimated pulmonary artery systolic pressure >35 mmHg. Patients were correctly allocated according to PCWP with an 87% sensitivity and a 90% specificity. Compared with the best single parameter estimating LVFP, a 17% relative increase in accuracy was achieved in patients with EF >50%. The model was prospectively validated in a testing group (n = 92): 80% sensitivity, 78% specificity. This sequential testing is useful to non-invasively predict LVFP in patients with LV dysfunction, especially in those with preserved EF.

Rapid Estimation of Left Ventricular Function Using Echocardiographic Speckle-Tracking of Mitral Annular Displacement

Left ventricular (LV) ejection fraction (EF) by transthoracic two-dimensional echocardiography is time-intensive and highly dependent on image quality. Mitral annular displacement (MAD) qualitatively correlates with EF and can be measured in patients with poor image quality and dropout. The authors hypothesized that speckle-tracking echocardiography (STE)-derived MAD could quantify EF accurately and tested this hypothesis using cardiac magnetic resonance (CMR) as a reference. One hundred eighteen patients undergoing clinical transthoracic echocardiography were screened, and 110 whose mitral annuli was sufficiently well-defined irrespective of LV endocardial visualization underwent CMR within 6 days (85 of 110 in 1 day). Reference CMR EF values were obtained using standard methodology. STE was used to track annular motion throughout the cardiac cycle in the apical 2-chamber and 4-chamber views. To establish the relationship between MAD and CMR EF and to obtain a formula to estimate EF from MAD, regression analysis was performed in a study group of 60 patients with a wide range of EFs. This formula was then used in an independent test group of 50 patients by comparing estimated MAD EF against CMR EF values using Pearson's correlation and Bland-Altman analyses. In the study group, STE MAD correlated highly with CMR EF and resulted in a formula relating MAD to EF. In the test group, estimated EF correlated well with CMR EF (4-chamber, R(2) = 0.64; 2-chamber, R(2) = 0.55), with near-zero bias and acceptable limits of agreement. Intraobserver and interobserver variability were between 5.8% and 12.7%. STE MAD is a clinically useful tool for quick, easy, robust, and accurate estimates of EF irrespective of LV endocardial definition.

Real-Time 3-Dimensional Echocardiographic Quantification of Left Ventricular Volumes: Multicenter Study for Validation With Magnetic Resonance Imaging and Investigation of Sources of Error

We sought to study: 1) the accuracy and reproducibility of real-time 3-dimensional echocardiographic (RT3DE) analysis of left ventricular (LV) volumes in a multicenter setting, 2) interinstitutional differences in relationship with the investigators' specific experience, and 3) potential sources of volume underestimation. Reproducibility and accuracy of RT3DE evaluation of LV volumes has not been validated in multicenter studies, and LV volumes have been reported to be underestimated compared to cardiac magnetic resonance (CMR) standard. A total of 92 patients with a wide range of ejection fractions underwent CMR and RT3DE imaging at 4 different institutions. Images were analyzed to obtain LV end-systolic volume (ESV) and end-diastolic volume (EDV). Reproducibility was assessed using repeated analyses. The investigation of potential sources of error included: phantom imaging, intermodality analysis-related differences, and differences in LV boundary identification, such as inclusion of endocardial trabeculae and mitral valve plane in the LV volume. The RT3DE-derived LV volumes correlated highly with CMR values (EDV: r = 0.91; ESV: r = 0.93), but were 26% and 29% lower consistently across institutions, with the magnitude of the bias being inversely related to the level of experience. The RT3DE measurements were less reproducible (4% to 13%) than CMR measurements (4% to 7%). Minimal changes in endocardial surface position (1 mm) resulted in significant differences in measured volumes (11%). Exclusion of trabeculae and mitral valve plane from the CMR reference eliminated the intermodality bias. The RT3DE-derived LV volumes are underestimated in most patients because RT3DE imaging cannot differentiate between the myocardium and trabeculae. To minimize this difference, tracing the endocardium to include trabeculae in the LV cavity is recommended. With the understanding of these intermodality differences, RT3DE quantification of LV volume is a reliable tool that provides clinically useful information.

Cardiac Magnetic Resonance Imaging After Stage I Norwood Operation for Hypoplastic Left Heart Syndrome

After the Norwood operation, a patient's suitability for proceeding to a bidirectional cavopulmonary connection (BCPC) is assessed by a combination of echocardiography and diagnostic cardiac catheterization. In this study, we describe the results of 37 patients who underwent cardiovascular magnetic resonance (MR) assessment before BCPC. Cardiovascular MR and echocardiography were performed in 37 infants with hypoplastic left heart syndrome before BCPC, and the findings were compared with surgical findings. MR assessment of ventricular function and valvar regurgitation were compared with echocardiography. MR exhibited high sensitivity and specificity for identification of neoaortic (sensitivity 86%, specificity 97%) and left pulmonary artery (sensitivity 100%, specificity 94%) obstruction. Echocardiography exhibited poor sensitivity for identification of vascular stenosis. The mean right ventricular ejection fraction calculated from the MR data was 50+/-10%. There was general agreement between MR and echocardiographic measures of ventricular function, although patients with good function on echocardiography demonstrated a wide range of ejection fractions. There was good agreement between MR and echocardiography for identification of valvar regurgitation. Cardiovascular MR can be used to define ventricular and valvar function and vascular anatomy in infants with hypoplastic left heart syndrome after the Norwood operation. We have shown how this information can be used to plan the BCPC and identify any revisions or additional valvar surgery.

Comparison of left ventricular ejection fraction calculated using attenuation-corrected and non-attenuation corrected images in gated cardiac spect imaging

Background: Gated single photon emission computed tomography (SPECT) imaging allows ventricular function measurements to be obtained simultaneously with the perfusion images. Ordinarily, non-attenuation corrected images are reviewed to assess myocardial perfusion and function. Attenuation correction using simultaneous transmission and emission data acquisition method has been used to better assess the perfusion images. This may alter the configuration of the left ventricular cavity and affect the calculation of left ventricular ejection fraction (LVEF). The objective of this study was to evaluate the effect of attenuation correction on the assessment of left ventricular function. Methods: Gated cardiac SPECT studies of 32 patients with single vessel coronary artery disease were reviewed. All the studies were acquired using the Hawkeye V3 system (GE Medical Systems, Milwaukee, WI). Emission images were acquired after the intravenous injection of 1.48 GBq (40 mCi) of Tc-99m Sestamibi at peak exercise or pharmacological stress. Transmission data in the form of cross-sectional patient attenuation images were acquired using high-resolution, 3-D X-ray imaging system. Only the stress images were assessed and processed to calculate the LVEF using attenuation corrected and non-attenuation corrected images. LVEF was calculated using the QGS software by the standard volume based method based on the edge detection technique. Results: There is a good correlation between the LVEF calculated using attenuation corrected and non-attenuation corrected images (regression line: y = 0.9886x - 0.2229, coefficient of linearity: 0.97) for a wide range of ejection fractions (range: 15% - 70%). A paired student's t-test revealed that there is no statistically significant difference between the 2 groups (p > 0.05). Conclusion: Our results indicate that there is no significant difference between the LVEF calculated using the attenuation corrected and non-attenuation corrected images and attenuation corrected images can be used to assess left ventricular function.

Does Gallbladder Ejection Fraction Predict Pathology after Elective Cholecystectomy for Symptomatic Cholelithiasis ?

Patients with symptomatic cholelithiasis are selected for elective cholecystectomy with the expectation that their symptoms will improve after operation. However, some patients fail to improve because their preoperative symptoms were not related to gallbladder disease. A test that would indicate the severity of gallbladder disease in patients with gallstones would therefore have great potential benefit. Twenty-five patients who presented as outpatients with episodic abdominal pain and gallstones were scheduled for elective cholecystectomy. On the day before operation patients underwent nuclear medicine cholescintigraphy with measurement of ejection fraction. All patients then underwent laparoscopic cholecystectomy. Pathologic specimens were reviewed by a pathologist who was blinded to the ejection fraction results and scored for degree of inflammation on a scale of zero to three. There was a wide range of ejection fractions measured (0-84%). There was, however, no correlation between ejection fractions and degree of gallbladder inflammation. We conclude that gallbladder ejection fraction does not predict the degree of gallbladder inflammation at the time of elective cholecystectomy. This test is therefore unlikely to predict which patients with cholelithiasis will have symptomatic relief after cholecystectomy.

Tube collapse and valve closure in ambulatory venous pressure regulation: studies with a mechanical model.

To determine the role of valve closure and column segmentation in ambulatory venous pressure regulation. Using a mechanical model consisting of a graduated adjustable valve and a collapsible tube, we studied the differential effects of valve closure and tube collapse on venous pressure regulation. By utilizing materials with differing wall properties for the infravalvular tube, the influence of wall property changes on tube function and pressure regulation was explored. Valve closure, per se, does not cause venous pressure reduction. Collapse of the tube below the valve is the primary pressure regulatory mechanism. The nonlinear volume-pressure relationship that exists in infravalvular tubes confers significant buffering properties to the collapsible tube, which tends to retain a near-constant pressure for a wide range of ejection fractions, residual tube volumes, and valve leaks. Changes in tube wall property affect this buffering action, at both the low and high ends of the physiological venous pressure range. The valve and the infravalvular venous segment should be considered together in venous pressure regulation. Tube collapse of the segment below the valve is the primary pressure regulatory mechanism. An understanding of the hydrodynamic principles involved in pressure regulation derived from this model will provide the basis for construction of more complex models to explore clinical physiology and dysfunction.

Tube Collapse and Valve Closure in Ambulatory Venous Pressure Regulation: Studies with a Mechanical Model

Purpose: To determine the role of valve closure and column segmentation in ambulatory venous pressure regulation. Methods: Using a mechanical model consisting of a graduated adjustable valve and a collapsible tube, we studied the differential effects of valve closure and tube collapse on venous pressure regulation. By utilizing materials with differing wall properties for the infravalvular tube, the influence of wall property changes on tube function and pressure regulation was explored. Results: Valve closure, per se, does not cause venous pressure reduction. Collapse of the tube below the valve is the primary pressure regulatory mechanism. The nonlinear volume-pressure relationship that exists in infravalvular tubes confers significant buffering properties to the collapsible tube, which tends to retain a near-constant pressure for a wide range of ejection fractions, residual tube volumes, and valve leaks. Changes in tube wall property affect this buffering action, at both the low and high ends of the physiological venous pressure range. Conclusions: The valve and the infravalvular venous segment should be considered together in venous pressure regulation. Tube collapse of the segment below the valve is the primary pressure regulatory mechanism. An understanding of the hydrodynamic principles involved in pressure regulation derived from this model will provide the basis for construction of more complex models to explore clinical physiology and dysfunction.