Ejection Fraction Units Research Articles

Aortic flow conditions predict ejection efficiency in the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

The Windkessel model of the cardiovascular system, both in its original wind-chamber and flow-pipe form, and in its electrical circuit analog has been used for over a century to modeled left ventricular ejection conditions. Using parameters obtained from aortic flow we formed a Flow Index that is proportional to the impedance of such a "circuit". We show that the impedance varies with ejection fraction (EF) in a manner characteristic of a resonant circuit with multiple resonance points, with each resonance point centrally located in a small range of EF values, i.e., corresponding to multiple contiguous EF bands. Two target populations were used: (I) a development group comprising male and female subjects (n=112) undergoing cardiovascular magnetic resonance (CMR) imaging for a variety of cardiac conditions. The Flow Index was developed using aortic flow data and its relationship to left ventricular EF was shown. (II) An illustration group comprised of female subjects from the Women's Ischemia Syndrome Evaluation (WISE) (n=201) followed for 5 years for occurrence of major adverse cardiovascular events (MACE). Flow data was not available in this group but since the Flow Index was related to the EF we noted the MACE rate with respect to EF. The EFs of the development population covered a wide range (9%-76%) traversing six Flow Index resonance bands. Within each Flow Index resonance band the impedance varied from highly capacitive at the lower range of EF through minimal impedance at resonance, to highly inductive at the higher range of EF, which is characteristic of a resonant circuit. When transitioning from one EF band to a higher band, the Flow Index made a sudden transition from highly inductive to capacitive impedance modes. MACE occurred in 26 (13%) of the WISE (illustration) population. Distance in EF units (Deltacenter) from the central location between peaks of MACE activity was derived from EF data and was predictive of MACE rate with an area under the receiver operator curve of 0.73. Of special interest, Deltacenter was highly predictive of MACE in the sub-set of women with EF >60% (AUC 0.79) while EF was no more predictive than random chance (AUC 0.48). A Flow Index that describes impedance conditions of left ventricular ejection can be calculated using data obtained completely from the ascending aorta. The Flow Index exhibits a periodic variation with EF, and in a separate illustration population the occurrence of MACE was observed to exhibit a similar periodic variation with EF, even in cases of normal EF.

Synergistic Effects of Combined Cell Therapy for Chronic Ischemic Cardiomyopathy

BackgroundBoth bone marrow–derived mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) improve left ventricular remodeling in porcine models and clinical trials. Using xenogeneic (human) cells in immunosuppressed animals with acute ischemic heart disease, we previously showed that these 2 cell types act synergistically. ObjectivesTo more accurately model clinical applications for heart failure, this study tested whether the combination of autologous MSCs and CSCs produce greater improvement in cardiac performance than MSCs alone in a nonimmunosuppressed porcine model of chronic ischemic cardiomyopathy. MethodsThree months after ischemia/reperfusion injury, Göttingen swine received transendocardial injections with MSCs alone (n = 6) or in combination with cardiac-derived CSCs (n = 8), or placebo (vehicle; n = 6). Cardiac functional and anatomic parameters were assessed using cardiac magnetic resonance at baseline and before and after therapy. ResultsBoth groups of cell-treated animals exhibited significantly reduced scar size (MSCs −44.1 ± 6.8%; CSC/MSC −37.2 ± 5.4%; placebo −12.9 ± 4.2%; p < 0.0001), increased viable tissue, and improved wall motion relative to placebo 3 months post-injection. Ejection fraction (EF) improved (MSCs 2.9 ± 1.6 EF units; CSC/MSC 6.9 ± 2.8 EF units; placebo 2.5 ± 1.6 EF units; p = 0.0009), as did stroke volume, cardiac output, and diastolic strain only in the combination-treated animals, which also exhibited increased cardiomyocyte mitotic activity. ConclusionsThese findings illustrate that interactions between MSCs and CSCs enhance cardiac performance more than MSCs alone, establish the safety of autologous cell combination strategies, and support the development of second-generation cell therapeutic products.

Defining the real-world reproducibility of visual grading of left ventricular function and visual estimation of left ventricular ejection fraction: impact of image quality, experience and accreditation

Left ventricular function can be evaluated by qualitative grading and by eyeball estimation of ejection fraction (EF). We sought to define the reproducibility of these techniques, and how they are affected by image quality, experience and accreditation. Twenty apical four-chamber echocardiographic cine loops (Online Resource 1–20) of varying image quality and left ventricular function were anonymized and presented to 35 operators. Operators were asked to provide (1) a one-phrase grading of global systolic function (2) an “eyeball” EF estimate and (3) an image quality rating on a 0–100 visual analogue scale. Each observer viewed every loop twice unknowingly, a total of 1400 viewings. When grading LV function into five categories, an operator’s chance of agreement with another operator was 50 % and with themself on blinded re-presentation was 68 %. Blinded eyeball LVEF re-estimates by the same operator had standard deviation (SD) of difference of 7.6 EF units, with the SD across operators averaging 8.3 EF units. Image quality, defined as the average of all operators’ assessments, correlated with EF estimate variability (r = −0.616, p < 0.01) and visual grading agreement (r = 0.58, p < 0.01). However, operators’ own single quality assessments were not a useful forewarning of their estimate being an outlier, partly because individual quality assessments had poor within-operator reproducibility (SD of difference 17.8). Reproducibility of visual grading of LV function and LVEF estimation is dependent on image quality, but individuals cannot themselves identify when poor image quality is disrupting their LV function estimate. Clinicians should not assume that patients changing in grade or in visually estimated EF have had a genuine clinical change.Electronic supplementary materialThe online version of this article (doi:10.1007/s10554-015-0659-1) contains supplementary material, which is available to authorized users.

Abstract 140: Effect of Transendocardial Autologous Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and Restore Cardiac Function in a Heart Failure Swine Model

Background: A cell combination of human mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) improves left ventricular (LV) performance to a greater degree than MSCs alone in post myocardial infarction swine. To advance the development of cell combination therapy, we administered autologous swine cells, and tested the hypothesis that transendocardial autologous CSCs/MSCs produces greater improvement of performance than MSCs in a rigorous model of heart failure due to post infarct LV remodeling. Methods: Gottingen mini-swine (n=28) underwent LAD coronary artery occlusion followed by reperfusion, and allowed to undergo LV remodeling for 90 days. Autologous MSCs were amplified from bone marrow and CSCs from right ventricular biopsies in each swine, and injections of either CSC/MSC combo (1M/200M, n=7), MSCs (200M, n=7), or placebo (Plasmalyte, n=6) were injected to the infarct-border zone via the NOGA system. Cardiac MRI and pressure volume loops were obtained before and after therapy. Results: Both cell groups had substantially reduced scar size (Combo –37.2.9± 5.4% vs MSCs –38.8±7.5% vs placebo −7.2±6.3, P=0.0001) and increased viable tissue (Combo +30.9±7% vs MSCs +41.8±10.5% vs placebo +7.7±4.5, P&lt;0.0001) relative to placebo. Ejection Fraction (EF) improved only in the Combo group (Combo +7.0±2.8 vs MSCs +3.4±1.3 vs placebo +1.2±1.6 EF units, P=0.04). Accompanying this EF restoration was a substantial improvement in the Combo group in stroke volume (Combo +47.2±11.1% vs MSCs +32.6±12.0% vs placebo +10.8±4.5, P&lt;0.0001), cardiac output (Combo +35.9±7.6% vs MSCs 41.9±26.5% vs placebo −16.4±6.6%, P=0.01) and diastolic strain rate (Combo +18.9±8.6% vs MSCs 14.0±8.8% vs placebo −14.9±9.5%, P=0.03). Conclusions: Combination cell therapy and MSCs alone dramatically reduce scar size in a swine model of chronic ischemic cardiomyopathy. In contrast, combination therapy has much greater impact on functional recovery, increasing EF to [near normal] levels. These findings illustrate that interactions between ckit+ CSCs and MSCs result in substantial enhancement in cardiac performance, establish the safety of autologous cell combination strategies, and support the development of an advanced second generation cell therapeutic product.

Diastolic functional class improvement is associated with more favorable outcomes in patients with acute nonischemic cardiomyopathy

Background: Patients with recent onset non-ischemic cardiomyopathy (ROCM) have variable clinical course related to left ventricular (LV) systolic recovery. It is unknown if temporal changes in diastolic function (DF) class can predict outcomes independent of LV systolic functional recovery in these patients. Methods: In the multicenter IMAC-2 (Intervention in Myocarditis and Acute Cardiomyopathy) study, there were 147 patients with ROCM (ejection fraction (EF) ≤40%, <6 months of symptoms) consistent with idiopathic cardiomyopathy or myocarditis who were prospectively studied by echocardiography. Systolic function was measured by biplane Simpson's rule EF and DF by mitral inflow velocities and mitral annular tissue Doppler at presentation and 6-month follow-up. Cox proportional hazards modeling was used to risk-adjust comparisons for the combined endpoint of death, transplantation and heart failure hospitalization. Results: Of 147 patients, (mean age 46±14 yrs, 40% female), baseline LVEF was 23±8%. At 6-months, LVEF improved to 41±12%, with 68% increasing by at least 10% EF units. DF improved in 55%, was unchanged in 27% and worsened in 13%. Over a mean follow-up of 1.8±1.2 yrs, there were 3 deaths, 4 transplants and 11 heart failure hospitalizations. LVEF at 6 months (HR=0.95, 95% CI 0.92-0.99,p=0.03) and improvement or maintaining DF class at 6-months were independently associated with lower likelihood for the combined end-point (HR=0.26, 95% CI 0.09-0.73, p=0.01). ![Figure][1] 6-Month Diastolic function and outcomes Conclusion: In patients with ROCM, improvement in or maintaining DF class was associated with more favorable outcomes, independent of LV systolic functional recovery. The association of DF with clinical outcomes suggest DF as a potential important prognostic marker in these patients. [1]: pending:yes

Correlation of Trabeculae and Papillary Muscles With Clinical and Cardiac Characteristics and Impact on CMR Measures of LV Anatomy and Function

The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity.

Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial

c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461. This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. University of Louisville Research Foundation and National Institutes of Health.

Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated Cardiomyopathy: Results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 Study

We sought to determine clinical and demographic predictors of recovery of left ventricular function for subjects with recent onset cardiomyopathy (ROCM). Although ROCM is a frequent reason for consultation and transplantation referral, its prognosis and natural history on contemporary therapy are unknown. In the multicenter IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study, subjects with a left ventricular ejection fraction (LVEF) of ≤0.40, fewer than 6 months of symptom duration, and an evaluation consistent with idiopathic dilated cardiomyopathy or myocarditis were enrolled. LVEF was reassessed at 6 months, and subjects were followed up for 4 years. LVEF and event-free survival were compared by race, sex, and clinical phenotype. The cohort of 373 persons was 38% female and 21% black, with a mean age of 45 ± 14 years. At entry, 91% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 82% were receiving beta-blockers, which increased to 92% and 94% at 6 months. LVEF was 0.24 ± 0.08 at entry and 0.40 ± 0.12 at 6 months (mean increase: 17 ± 13 ejection fraction units). Transplant-free survival at 1, 2, and 4 years was 94%, 92%, and 88%, respectively; survival free of heart failure hospitalization was 88%, 82%, and 78%, respectively. In analyses adjusted for sex, baseline LVEF, and blood pressure, LVEF at 6 months was significantly lower in blacks than in nonblacks (p = 0.02). Left ventricular end-diastolic diameter at presentation was the strongest predictor of LVEF at 6 months (p < 0.0001). Outcomes in ROCM are favorable but differ by race. Left ventricular end-diastolic diameter by transthoracic echo at presentation was most predictive of subsequent myocardial recovery. (Genetic Modulation of Left Ventricular Recovery in Recent Onset Cardiomyopathy; NCT00575211).

Angiography-based prediction of outcome after coronary artery bypass surgery versus changes in myocardial perfusion scintigraphy

The present study compared the clinical prediction of the effect of coronary artery bypass grafting (CABG) on coronary blood flow and left ventricular ejection fraction (LVEF) with changes in gated myocardial perfusion scintigraphy. A prospective group of 92 patients underwent myocardial perfusion scintigraphy before and 6 months after CABG, the results being kept secret from the surgeon. Based on clinical and angiographic findings, the surgeons filled in a questionnaire indicating the predicted changes in coronary blood flow in each of the three coronary artery territories and in the LVEF. Symptomatic improvement was present in nearly all the patients. Following CABG, the perfusion defects were reduced in around two-thirds and normalized in one-third of the territories clinically predicted to improve. Improved perfusion for territories not predicted to improve was slightly lower, and correlations between predicted and observed regional changes in coronary blood flow and perfusion defects were poor. LVEF increased (by over five ejection fraction units) in almost half of the patients, but with no correlation between the predicted and the observed changes. Based on clinical and angiographic findings, the marked improvements after CABG in cardiac perfusion and function are poorly predicted.

Prognostic implications of post-stress ejection fraction decrease detected by gated SPECT in the absence of stress-induced perfusion abnormalities

The prognostic meaning of a post-stress ejection fraction (EF) decrease detected by perfusion gated SPECT is still unclear.We therefore followed up patients with post-stress EF decrease in the absence of stress-induced perfusion abnormalities. We prospectively enrolled 57 consecutive patients with post-stress EF drop ≥ 5 EF units and summed difference score (SDS) ≤ 1. They were followed up for more than 1 year and their outcome was compared with a group of sex- and age-matched controls with the same SDS but without EF decrease. During follow-up there were 13 events (1 cardiac death, 1 non-fatal myocardial infarction, 1 congestive heart failure and 10 late revascularizations). In the control group we registered six events. There was a significant difference (p<0.0001) between the event-free survival curves of the two groups. The event rate of patients with post-stress EF decrease ≥ 5 EF units is relatively high and is significantly worse than that of a control group of patients with similarly normal SDS but without EF changes. Therefore, a post-stress EF decrease without stress-induced perfusion abnormalities should be cautiously interpreted.

Reliability of myocardial perfusion gated SPECT for the reproducible evaluation of resting left ventricular functional parameters in long-term follow-up

Perfusion gated single photon emission computed tomography (SPECT) can assess with good reproducibility left ventricular (LV) volumes and ejection fraction (EF). Whether this reproducibility is maintained in long-term follow-up is unknown. We compared LV end-diastolic (ED) and end-systolic (ES) volumes (V) as well as EF calculated using gated SPECT and QGS software in 103 coronary artery disease patients studied twice at > 1-year interval because of standard clinical indications. Patients were divided into two groups: (A) 67 patients without major clinical changes and with stable resting perfusion and (B) 36 with modified clinical status or resting perfusion. The relationship between gated SPECT 2 EF (=y) and gated SPECT 1 EF (=x) was for group A: y=0.91 x + 5.34, r=0.92, p<0.0001, SEE=4 and for group B: y=0.67 x + 13.6, r=0.63, p<0.0001, SEE=10. The 95% limit of agreement was 8 EF units for group A and 20.6 EF units for group B. For EDV, the 95% limit of agreement was 22 ml for group A and 52 ml for group B. For ESV, the 95% limit of agreement was 13 ml for group A and 44 ml for group B. In stable patients with an unmodified resting perfusion pattern the functional parameters derived from perfusion gated SPECT have good reproducibility even after a prolonged time interval. This supports the value of gated SPECT for serial evaluations of LV function.

Cardiac Resynchronization Therapy (and Multisite Pacing) in Pediatrics and Congenital Heart Disease: Five Years Experience in a Single Institution

Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in adults with heart failure, but experience in pediatrics and congenital heart disease (CHD) is limited in terms of patient numbers and follow-up. We sought to determine the functional assessment and clinical outcomes in pediatric and CHD CRT patients followed uniformly at one institution. Retrospective review of 60 consecutive patients who underwent CRT between 2002 and 2007. At implantation, median age was 15.0 years (5 months to 47 years). Overall, 46 patients had CHD (77%) and 14 had dilated cardiomyopathy. Prior to CRT, 92% were on heart failure treatment drugs and 55% had pacemakers. Median follow-up time was 0.7 years (1 day-5.3 years). Median QRS width decreased from 149 to 120 ms (P < 0.001). Median ejection fraction (EF) increased from 36% to 42% (P < 0.001) and improvement was particularly evident in the group with CHD. Of note, 8 of 13 patients with single ventricle morphology had a "strong CRT response," defined as either an improvement of 2-3 ordinal points in NYHA classification and/or increased ventricular function by >or= 10 EF units. Overall, an improvement in functional status was observed in 39 of 45 patients (87%) with sufficient follow-up data. Children and CHD patients treated with CRT have acute improvement in ventricular function, but implantation may require individualized planning and unconventional approaches. Future important goals include preimplant determination of CRT responders in pediatric and CHD patients, optimizing lead placement and programing, as well as long-term CRT device management issues.

Is 16-frame really superior to 8-frame gated SPECT for the assessment of left ventricular volumes and ejection fraction? Comparison of two simultaneously acquired gated SPECT studies

Conflicting data exist about the difference between 8- and 16-frame gated single-photon emission computed tomography (SPECT) left ventricular volumes and ejection fraction (EF); moreover, the influence of framing on detection of stress-induced functional changes is unknown. In 133 patients, two separate gated SPECT studies, one with 8 and one with 16 frames, were simultaneously acquired during a single gantry orbit using dedicated software. In 33 of 133 patients, two additional studies (with 8 and 16 frames, respectively) were acquired using arrhythmia rejection. Left ventricular EF and volumes were calculated using the QGS software. Stress-induced ischemia was identified on summed perfusion images. Arrhythmia-rejection did not influence volumes and EF independently of framing rate. Using data without arrhythmia-rejection, there was a significant difference in volumes and EF between 8 and 16 frames both in resting and post-stress gated SPECT. However, the difference was small: 2.6% for resting and 2.8% for post-stress EF. Both using 8 and 16 frames, there were significantly larger volumes and lower EF in patients with than without stress-induced ischemia. A stress-induced decrease >5 EF units was observed in 26 of 133 patients using 8 and in 23 of 133 using 16 frames, respectively, with finding agreement in 19 patients. Comparing two simultaneously acquired studies, the use of 16 instead of 8 frames has minor and predictable influence on functional data. Furthermore, there are no differences in the detection of stress-induced functional changes. The advantage of 16 over 8 frames in the daily clinical practice appears questionable.

Proportion of viable myocardium is more reliable than semi-quantitative score in predicting functional recovery: a pilot study of PET myocardial viability imaging

PET myocardial viability imaging is the “gold standard” for the non-invasive assessment of myocardial viability. The research aims to find out the best methods of imaging interpretation in predicting the postoperative functional recovery. Twenty-one CAD patients with multi-vessel involvement were recruited. All patients underwent gated myocardial perfusion imaging(G-MPI) and FDG PET myocardial imaging within 2 weeks before coronary artery bypass grafting. The postoperative G-MPI was performed in all patients 3 months after the surgery. Out of the total 420 segments, 164 segments of ischemic myocardium were detected by preoperative G-MPI. Among them, 93 ischemic segments were identified as non-viable (difference score≥GT0) and the rest 71 segments were identified as viable(difference score<0). The proportion of viable segments (the ratio of viable segments versus ischemic segments) and summed difference score of metabolism to perfusion were calculated. The patients were further divided into 2 groups according to the proportion of viable myocardium: group I (the proportion≥GT50%, 12 cases) and group II (the proportion<50%, 9 cases) while another division was made according to SDS: group A (SDS≥GT0), group B (-5≤GTSDS<0) and group C (SDS<-5). The diagnostic accuracy of proportion of viable segments and SDS in predicting the post-revascularization improvement in the left ventricular ejection fraction by at least 5 or more ejection fraction units was 88.89% (8/9) and 55.56% (5/9) respectively. It is concluded that both approaches allow accurate evaluation of myocardial viability. Furthermore, the proportion of viable myocardium is more reliable in predicting the postoperative functional recovery.

Isosorbide Dinitrate and Hydralazine in a Fixed-Dose Combination Produces Further Regression of Left Ventricular Remodeling in a Well-Treated Black Population With Heart Failure: Results From A-HeFT

Isosorbide dinitrate combined with hydralazine therapy compared with placebo in patients with heart failure resulted in a sustained increase in left ventricular (LV) ejection fraction (EF) indicative of regression of LV remodeling in the first Vasodilator-Heart Failure Trial (V-HeFT-I) in patients receiving only digoxin and diuretic. In the African-American Heart Failure Trial (A-HeFT) a fixed-dose combination resulted in a 43% reduction in mortality in 1050 black patients with heart failure already treated with recommended neurohormonal inhibiting drugs. Whether the fixed-dose combination produces a further regression of LV remodeling when added to renin-angiotensin and sympathetic inhibitors has not been documented. Echocardiograms at baseline and 6 months after randomization to placebo or a fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) were analyzed in 678 A-HeFT participants in a core laboratory. LVEF rose by 2.8 EF units in the FDC I/H group versus 0.8% in the control group (P < .01), LV mass index fell by 7.4 g/m2 in the FDC I/H group versus an increase of 1.4 g/m2 in the placebo group (P < .05), LV diastolic transverse diameter fell by 2.2 mm in FDC I/H and was unchanged in placebo (P < .01), and the LV systolic and diastolic sphericity indices improved in the FDC I/H group but remained unchanged in the placebo group. The mean plasma B-type natriuretic peptide (BNP) also measured in a core laboratory fell in the FDC I/H group by 39 pg/mL compared with 8 pg/mL in the placebo group (P = .05). A fixed-dose combination of I/H produces regression of LV remodeling when added to background therapy with renin-angiotensin and sympathetic inhibitors in black patients with heart failure. This remodeling benefit may explain at least in part the mortality reduction in A-HeFT.

Management of patients with implantable cardioverter defibrillators at emergency departments

Background: With rapid improvements in technology and accumulation of clinical evidence, the implantable cardioverter defibrillator (ICD) has become a standard treatment for either primary or secondary prevention of sudden cardiac...

Echocardiographic Strain Imaging for Myocardial Viability

Echocardiographic strain imaging was introduced by Heimdal et al in 19981 as a means to calculate myocardial regional function from tissue Doppler velocity data.2,3 Strain imaging is a variation of the previous concept of tissue Doppler myocardial velocity gradient, which calculates regional thickening independent of passive whole heart motion.4,5 Because routine clinical evaluation of regional function is usually by visual wall-motion assessment, strain imaging has great promise to improve objective quantification of regional function. Strain imaging calculates deformation, which translates clinically to percent shortening in the longitudinal dimension (assessed from apical views) or percent thickening in the radial dimension (assessed from parasternal views).1,6,7 Theoretically, it has the important advantage of differentiating active myocardial motion from passive translational or tethering movements that other echocardiographic-Doppler approaches cannot differentiate. Indeed, there have been literally hundreds of publications over the last 10 years detailing a wide range of experimental and potential clinical applications of strain imaging; however, currently, few centers have adopted strain imaging in their routine clinical practice, preferring visual “eyeball” assessment, even though this is inherently subjective and requires a high level of experience and training.8 An important question remains: Is it now time for strain imaging to be adopted in a widespread clinical sense? Articles pp 3892 and 3901 Two important articles are contained in this issue of Circulation that address the application of strain imaging as a tool to assess myocardial viability: an animal study of experimental ischemia and infarction by Lyseggen et al9 and a clinical study using dobutamine echocardiography with outcome data after revascularization by Hanekom et al.10 The article by Lyseggen et al illustrates the additive value of strain imaging in an elegant open-chest animal model of coronary occlusion and reperfusion. Echocardiographic strain imaging was performed along with simultaneous dimensional …

Resynchronization Therapy in Pediatric and Congenital Heart Disease Patients: An International MultiCenter Study

Our objective was to evaluate the short-term safety and efficacy of cardiac resynchronization therapy (CRT) in children. Cardiac resynchronization therapy has been beneficial for adult patients with poor left ventricular function and intraventricular conduction delay. The efficacy of this therapy in the young and in those with congenital heart disease (CHD) has not yet been established. This is a multi-center, retrospective evaluation of CRT in 103 patients from 22 institutions. Median age at time of implantation was 12.8 years (3 months to 55.4 years). Median duration of follow-up was four months (22 days to 1 year). The diagnosis was CHD in 73 patients (71%), cardiomyopathy in 16 (16%), and congenital complete atrioventricular block in 14 (13%). The QRS duration before pacing was 166.1 +/- 33.3 ms, which decreased after CRT by 37.7 +/- 30.7 ms (p < 0.01). Pre-CRT systemic ventricular ejection fraction (EF) was 26.2 +/- 11.6%. The EF increased by 12.8 +/- 12.7 EF units with a mean EF after CRT of 39.9 +/- 14.8% (p < 0.05). Of 18 patients who underwent CRT while listed for heart transplantation, 3 improved sufficiently to allow removal from the transplant waiting list, 5 underwent transplant, 2 died, and 8 others are currently awaiting transplant. Cardiac resynchronization therapy appears to offer benefit in pediatric and CHD patients who differ substantially from the adult populations in whom this therapy has been most thoroughly evaluated to date. Further studies looking at the long-term benefit of this therapy in this population are needed.

Choosing Apical Long-axis Instead of Two-chamber View Gives More Accurate Biplane Echocardiographic Measurements of Left Ventricular Ejection Fraction: A Comparison with Magnetic Resonance Imaging

We sought to evaluate whether the use of apical long-axis (APLAX) rather than two-chamber (2CH) view, in combination with four-chamber (4CH) view, improved accuracy of biplane echocardiographic measurements of left ventricular (LV) ejection fraction (EF), using magnetic resonance imaging (MRI) as a reference standard. One hundred consecutive cardiac patients underwent cardiac MRI and 2D-echocardiography. Standard apical LV views were digitally acquired with baseline tissue harmonic imaging and low-power contrast echocardiography. Echo and MRI LV volumes were calculated by manual tracing and disc summation methods. Feasiblity for biplane volume measurements increased with the use of APLAX. Precontrast limits of agreement (LOA) for EF compared to MRI were -19.1 to 9.0 % (EF units) using 2CH, narrowing to -14.6 to 6.7% using the APLAX. With contrast, corresponding LOAs narrowed from -10.5 to 6.1%, to -7.3 to 3.8%, respectively. The improved accuracy with APLAX was evident regardless of image quality, previous MI and regional LV dyssynergy. Both intra- and interobserver variability improved by substituting 2CH with APLAX view. Using APLAX rather than 2CH in combination with 4CH view improved feasibility, accuracy and reproducibility of biplane echocardiographic EF measurements in cardiac patients, even with optimisation of endocardial borders by contrast.

Simple Clinical Criteria to Determine the Prognosis of Heart Failure

To determine whether easily obtained clinical parameters serve as predictors of survival in patients with congestive heart failure. Several scoring systems to predict heart failure survival have been developed; however, many of these deal principally with transplant recipients or do not account for a patient's response to therapy. A total of 680 patients with an ejection fraction of less than 40% were included in the analysis. Baseline assessments were performed and treatment regimens were identified; patients were then followed for up to 5 years. Univariate and multivariate Cox regression models were used to determine clinically important predictors of survival. Kaplan-Meier survival functions for patients with and without the prognostic variable were constructed and mortality was calculated at 1 year and 5 years. Ejection fraction improvement at 6 months, diabetes mellitus, age, serum creatinine, and blood urea nitrogen (BUN) were significant predictors for survival in the univariate model. Ejection fraction improvement, age, and BUN were significant predictors in the multivariate model. These findings were used to construct a model for predicting patient mortality. Improved ejection fraction (>15 ejection fraction units) gave a 1-year mortality of 2% and a 5-year mortality of 11%. Mortality rates according to patient age and BUN levels were also calculated. Ejection fraction improvement was the most important predictor for survival in patients with systolic dysfunction; monitoring ejection fraction changes through repeat echocardiograms has important prognostic value. In patients without ejection fraction improvement, age and renal function are important survival determinants.