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Sudden death in the year following myocardial infarction. Relation to ventricular premature contractions in the late hospitals phase and left ventricular ejection fraction.

Both depressed left ventricular ejection fraction and ventricular arrhythmias have been associated with a poor prognosis following acute myocardial infarction. To assess the relative role of each of these parameters in predicting mortality in the early period after hospitalization for myocardial infarction, 24 hour ambulatory electrocardiographic tape recordings and gated cardiac blood pool scans were obtained in 81 patients approximately two weeks after their admission to the hospital for myocardial infarction. Lown class 0 to II ventricular premature contractions during this period were classified as uncomplicated ventricular arrhythmias and Lown class III to V ventricular premature contractions were classified as complicated ventricular arrhythmias. Ejection fraction was calculated from biplane images of gated cardiac blood pool scans. In 35 patients the ejection fraction was greater than or equal to 0.40; only three of these had complicated ventricular arrhythmias. In 45 patients the ejection fraction was less than 0.40; 26 of these had complicated ventricular arrhythmias. Eight patients had documented ventricular fibrillation or instantaneous death during a mean 7.0 moonth (range 2 to 16 months) follow-up period outside the hospital. Although the number of patients studied was small, and there were only eight sudden deaths, life table analysis projected a one year mortality of 66 per cent in patients with complicated ventricular arrhythmias and 31 per cent in patients with an ejection fraction less than 0.40. All eight patients who died suddenly were in the subgroup of 26 patients with an ejection fraction less than 0.40 and complicated ventricular arrhymias; none was in the subgroup of 19 patients with an ejection fraction less than 0.40 and uncomplicated ventricular arrhythmias (P less than 0.02). Although a low ejection fraction may suggest a poor prognosis following myocardial infarction, the presence of complicated ventricular arrhythmias significantly increases the risk of sudden cardiac death in the early period after hospitalization in patients with low ejection fraction.

Arrhythmias, Cardiac

A simple and rapid non-invasive radioisotope method to determine ventricular ejection fractions and cardiopulmonary transit times.

Ejection fractions and cardiopulmonary transit times were measured in 20 hospital patients by means of intravenously injected 99mTc-radiocardiography. Time activity curves from the regions of the whole heart, superior vena cava, right atrium, right ventricle, right lung, left atrium and left ventricle were drawn and analyzed by using the modified gamma function fitting method. The comparison between the ejection fractions determined from the whole heart curves and those from the ventricular curves shows a correlation coefficient of 0.93 for the right ventricle and of 0.90 for the left, although there was a systematic difference between the determinations. The analysis of the single ventricular curves gave about 10% higher values than those obtained from the whole heart curves. The cardiopulmonary parameters measured from the whole heart curves for 16 normal subjects the following results gave: right ventricular ejection fraction=0.57+/-0.08 left ventricular ejection fraction=0.62+/-0.08 pulmonary mean transit time=6.1+/-1.1 heart-beats intracardiac mean transit time=10.5+/-1.8 heart-beats right/left ventricular volume=1.10+/-0.09 These values agree closely with the data accumulated using more elaborate methods. The method presented here is simple to perform, it is non-invasive, time-saving, inexpensive, easy to analyze and suitable for exercising subjects and for bed-side measurements. Data assembly and analysis are easily automated so that results are obtainable immediately after measurements.

Adult

Value of the QRS complex in assessing left ventricular ejection fraction.

The relation between electrocardiographic findings and the angiographic left ventricular ejection fraction and the augmented ejection fraction after a premature ventricular contraction was investigated in 73 patients with documented chronic coronary artery disease. The patients were separated into four groups according to the presence or absence of abnormal Q waves. Twenty-four patients had diaphragmatic myocardial infarction, 21 had anterior myocardial infarction, 15 had both and 13 had no myocardial infarction. There was no statistically significant differences in cardiac index, left ventricular end-diastolic pressure or number of coronary vessels showing critical narrowing in the four groups. The sum of R waves (in mv) in leads aVL, aVF and V1 to V6 (sigmaR) was correlated with the ejection fraction (EF) and the augmented ejection fraction (EFa). EF in percent = 6.6 sigmaR mv + 9.4 (no. =73, r = 0.61); and EFa in percent = 8.6 sigmaR mv + 11.0 (no. = 73, r = 0.77). Among patients with sigmaR of less than 4.0 mv, augmented ejection fraction was less than 0.45 in 73 percent; among patients with sigmaR of 4.0 mv or more the augmented ejection fraction was greater than 0.45 in 93 percent (P less than 0.001). Thus, the sigmaR, calculated from six precordial and two augmented leads in patients with chronic coronary artery disease, correlated with both ejection fraction and augmented ejection fraction. The electrocardiogram in patients with coronary artery disease may prove useful as a simple, readily available and noninvasive guide in the assessment of left ventricular function in patients with coronary artery disease.

Blood Pressure

Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction.

The left ventricular ejection fraction was determined serially with radioisotope angiography in 63 patients with acute myocardial infarction. After the peripheral injection of a bolus of technetium-99m, precordial radioactivity was recorded with a gamma scintillation camera and the ejection fraction calculated from the high frequency left ventricular time-activity curve. Since this technique requires no assumptions with respect to left ventricular geometry, it is particularly useful in patients with segmental left ventricular dysfunction. Serial measurements during the first 5 days after hospital admission were made in 50 patients, 30 of whom were studied during the subsequent 2 to 39 months (mean 19.9 months). Late follow-up serial studies were also performed in an additional 13 patients who had only one measurement of the left ventricular ejection fraction during the early postinfarction period. Early after infarction, the left ventricular ejection fraction was normal (more than 0.52) in only 15 of the 63 patients, and averaged 0.52 +/- 0.05 (standard deviation) in the 27 patients with an uncomplicated infarct. The ejection fraction was reduced in 24 patients with mild to moderate left ventricular failure (0.40 +/- 0.05, P less than 0.0001) and in the 12 patients with overt pulmonary edema (0.33 +/- 0.07, P less than 0.0001). In 35 patients the ejection fraction correlated with the mean pulmonary arterial wedge pressure (r = 0.72). In 15 patients with normal left ventricular wall motion by heart motion videotracking, the ejection fraction was significantly higher (0.53 +/- 0.08) than in the 26 patients with regional left ventricular dysfunction (0.41 +/- 0.10, P less than 0.0001). During the early postinfarction period, the left ventricular ejection fraction improved in 55 percent of patients and remained unchanged or decreased in 45 percent. A further increase in the ejection fraction was noted in 61 percent of patients during the late follow-up period. Patients with an initially low or decreasing ejection fraction had a significantly greater incidence of early mortality and left ventricular dysfunction (P less than 0.02) than those whose ejection fraction was normal or improved to normal early after infarction. These data indicate that the ejection fraction is a sensitive indicator of left ventricular function after acute myocardial infarction and that serial measurements are helpful in predicting early mortality and morbidity.

Acute Disease

Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability.

The intrinsic variability and accuracy of left ventricular ejection fraction determined by multiple gated cardiac blood pool imaging was evaluated in 83 patients. Ejection fraction by gated studies correlated well with data from first pass radionuclide angiocardiography (r = 0.94) and from contrast angiography (r = 0.84). Intra- and interobserver variabilities of absolute ejection fraction were minimal (mean +/- standard deviation 1.4 +/- 1.2 and 1.6 +/- 1.5 percent, respectively) and were not different for normal (ejection fraction 55 percent or greater) and abnormal patients. Ejection fraction was determined twice in 70 patients: on the same day at intervals separated by 1 to 2 hours (41 patients) and on 2 different days (29 patients). Ejection fraction ranged from 18 to 91 percent and was normal in 37 patients. There was no difference in mean serial variabilities of absolute ejection fraction for all repeat studies performed on the same and separate days (3.3 +/- 3.1 versus 4.3 +/- 3.1 percent (not significantly different). The mean variability of absolute ejection fraction for repeat studies in normal patients was significantly greater than in abnormal patients (5.4 +/- 4.4 versus 2.1 +/- 2.0 percent, P less than 0.01). The incidence rate of absolute interstudy changes of 5 percent or more was significantly higher in normal than in abnormal patients (P less than 0.01). This differential variability should be considered in interpreting sequential changes in left ventricular ejection fraction. To be attributed to nonrandom physiologic alterations, the absolute change in ejection fraction should be 10 percent or more in normal patients and 5 percent or more in abnormal patients.

Angiocardiography

Percentage of shortening of the echocardiographic left ventricular dimension. Its use in determining ejection fraction and stroke volume.

The percentage of shortening of the echocardiographic left ventricular dimension (% delta D) was prospectively evaluated in 42 patients without detectable asynergy during diagnostic cardiac catheterization and was found to correlate well with angiographic ejection fraction (r = 0.90). Ejection fraction was calculated as the product of % delta D X 1.7 or as % delta (D2), both formulae having similar degrees of accuracy and a better correlation with the angiographic determination than conventional formulae. Ejection fractions (angiographic and echocardiographic) of 51 percent or greater were always associated with a % delta D of 30 percent or more. In five patients the echocardiographically derived ejection fractions were normal (greater than or equal to 51 percent), while the angiographic ejection fractions were reduced; four of these patients had valvular regurgitation. End-diastolic volumes were calculated from end-diastolic echocardiographic dimensions utilizing a linear regression equation derived from correlating the end-diastolic echocardiographic dimension with the end-diastolic volume in 27 patients without valvular regurgitation (end-diastolic echocardiographic dimension ranged from 3.7 to 8.2 cm). The value for stroke volume determined as the product of calculated end-diastolic volume times ejection fraction correlated with the angiographically determined stroke volume (r = 0.88; standard error of estimate, +/- 11 ml) better than the value for stroke volume derived from conventional echocardiographic formulae.

Adolescent

[Radioisotope measurement of left ventricular ejection fraction. Comparison with results of cineangiocardiography].

The combination of radiocardiography with scintigraphy of the cavities of the heart allows us to calculate the effective systemic ejection fraction. The systolic volume effectively ejected into the systemic circulation is obtained from radiocardiography using Stewart-Hamilton's principle. It is correlated with the left ventricular end-diastolic volume as calculated by planimetry on the scintigraphic record of the cavities of the heart, making due allowance for the geometrical axis of the heart. The ejection fraction measured by this isotope method has been compared with the ejection fraction measured by selective left ventricular cineangiography, both measurements being carried out at an interval of less than 48 hours in 100 patients without valvular disease. The results show an excellent correlation between the two methods (r = 0.94). In the 15 cases where the haemodynamic status of the ventricule appeared to be normal, the ejection fraction meastured by the two techniques was 0.65 +/- 0.04 and 0.66 +/- 0.04 respectively. In those patients with valve disorders with incompetence, the effective systemic ejection fraction is always lower than the total ejection fraction given by cineangiography. The difference corresponds with the fraction of the blood volume which is regurgitated.

Angiocardiography

Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease.

A reproducible noninvasive technique for measuring righ ventricular ejection fraction was developed using first pass quantitative radionuclide angiocardiography. Studies were obtained in the anterior position with a computerized multicrystal scintillation camera with high count rate capabilities. Right ventricular ejection fraction was calculated on a beat to beat basis from the high frequency components of the background-corrected right ventricular time-activity curve. In 50 normal adults, right ventricular ejection fraction averaged 55 percent (range of 45 to 65 percent). This radionuclide measure of right ventricular function was reproducible, with minimal inter- and intraobserver variability, and was sensitive to changes in inotropic state induced with isoproterenol. In 36 patients with chronic obstructive pulmonary disease, right ventricular ejection fraction ranged from 19 to 71 percent. All 10 patients with corpulmonale, as well as 9 additional patients, had an abnormal right ventricular ejection fraction. Arterial oxygen tension and forced expiratory volume were depressed significantly more in patients with abnormal right ventricular ejection fraction than in subjects with normal right ventricular function. There was no relation between abnormalities in right and left ventricular ejection fraction.

Adult

Profiles of radionuclide left ventricular ejection fraction changes induced by supine bicycle exercise in normals and patients with coronary heart disease.

This paper presents the profiles of left ventricular ejection fraction (EF) during and following supine bicycle exercise in normal subjects and in patients with coronary heart disease, as well as the relationship of the described patterns to clinical parameters. Twenty normal men and 40 patients with coronary artery disease were studied using gated equilibrium radionuclide angiography (EQ-EF). In the normals, during exercise, EF increased by a mean of 25% of the resting value, with an increase of no less than 11%. The exercise-limiting symptom in patients with coronary artery disease was angina pectoris in 20 and fatique in the other 20 patients. In the angina patients, there was a mean decrease in EF of 20%, and in the other coronary artery disease patients ejection fraction change little. Only two patients with coronary artery disease increased from a normal resting value to peak exercise by more than 11%, and they had isolated right coronary lesions. An "overshoot" elevation of ejection fraction above resting levels was demonstrated following termination of exercise in most patients. The patients with a significant fall in exercise ejection fraction more frequently had abnormal exercise-induced ECG changes as well as abnormal left ventriculograms and more severe coronary artery disease at cardiac catheterization than the patients with little change in ejection fraction. We conclude that 1) normals could be separated from most patients with significant coronary artery disease in this study population; 2) ejection fraction must be measured at maximal exercise for it to have diagnostic value, since there could be normal rise before and after peak exercise and an abnormal response missed; and 3) the ejection fraction response to exercise reflects the severity of the underlying coronary artery disease. The described patterns of exercise-induced changes in left ventricular ejection fraction are important to consider when using this new technique to diagnose and evaluate patients with coronary artery disease.

Adult

Effect of a physical conditioning program upon left ventricular ejection fractions determined serially by a noninvasive technique.

6 clinically normal subjects underwent a 3-month physical conditioning program with the ejection fractions determined before and after physical conditioning using a scintillation probe. All subjects achieved a conditioning effect as evidenced by increased treadmill test duration after conditioning (mean duration before conditioning: 658 vs. 715 sec after conditioning; p less than 0.02). All 6 subjects increased resting ejection fractions after conditioning (mean ejection fraction before conditioning: 54.5 +/- 5.4%; mean ejection fraction after conditioning: 67.0 +/- 9.0%; p less than 0.01). Thus, an aerobic physical conditioning program appears to increase resting ejection fractions in normal subjects.

Adult

Proteomic patterns according to ejection fraction: an EMPEROR-programme analysis.

AIMS: Left ventricular ejection fraction (LVEF) has been incorporated as an inclusion criterion in HF trials. Patient's characteristics, event risk, and treatment response vary according to LVEF. A better understanding of the biological processes across LVEF is warranted. To study proteomic biomarker expression across LVEF using data from the EMPEROR-Programme. METHODS: Two thousand two hundred and fifty-four patients who had proteomic measurements available using 1134 proteins overlapping between the Explore 1536 and 3072 Olink® platforms were included. Main analyses were performed within the EMPEROR-Preserved dataset due to differences in entry criteria between EMPEROR-Preserved and EMPEROR-Reduced with higher entry N-terminal pro B-type natriuretic peptide (NT-proBNP) levels that varied by LVEF cut-offs in the latter. Protein concentrations were compared using ordinal logistic regression across LVEF categories: 41%-49%, 50%-59%, and ≥60%. The resulting β-coefficient indicates the change in the log-odds for the outcome of being in a lower LVEF category for every NPX unit in log2 scale. Analyses were adjusted for covariates and a false-discovery-rate (FDR) correction was applied. RESULTS: A total of 297 proteins exhibited a trend of expression across LVEF categories in EMPEROR-Preserved after adjustment for potential confounders and correction for test multiplicity. Of these, the top 10 proteins were: NT-pro BNP (β = 0.18, 95% CI 0.09-0.27), Wnt inhibitory factor-1 (β = 0.40, 95% CI 0.19-0.61), sialomucin core protein 24 (β = 0.48, 95% CI 0.22-0.74), phospholipid transfer protein (β = 0.38, 95% CI 0.17-0.59), natriuretic peptides B (β = 0.13, 95% CI 0.06-0.20), intercellular adhesion molecule 5 (β = 0.31, 95% CI 0.14-0.49), neural cell adhesion molecule 2 (β = 0.45, 95% CI 0.19-0.70), neural cell adhesion molecule L1-like protein (β = 0.45, 95% CI 0.19-0.71), interactor protein for cytohesin exchange factors 1 (β = 0.12, 95% CI 0.05-0.19), and 3-ketoacyl-CoA thiolase, peroxisomal (β = 0.17, 95% CI 0.07-0.26). The correlation between these proteins and LVEF was generally weak (Rho ≤0.2). CONCLUSIONS: Within EMPEROR-Preserved, the top differentially expressed circulating proteins suggest that pathways related to natriuretic peptides, cell-adhesion, and clonal haematopoiesis are overexpressed at mildly-reduced ejection fraction, but none of the proteins passed the 5%FDR cut-off, and the correlation between circulating proteins and LVEF was weak. These findings suggest that circulating proteins may not be a good discriminant of ejection fraction.

Humans

Regional ejection fraction: a quantative radionuclide index of regional left ventricular performance.

Radionuclide measurements of regional left ventricular ejection fraction were evaluated as a quantitative index of regional left ventricular function. Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography and left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms and without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening and extent of akinetic segments in corresponding regions of the contrast ventriculogram. Radionuclide and roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 +/- 3%, mean +/- SEM), hypokinesis (44 +/- 3%, p less than 0.0005) and akinesis (24 +/- 5%, p less than 0.005). We conclude that the left ventricular regional ejection provides a reliable quantitative assessment of regional left ventricular performance.

Adult

Molecular Pathways, Target Landscape, and Translational Models in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a substantial global health burden and the greatest unmet medical need for cardiovascular diseases. It is marked by pronounced clinical heterogeneity and complex multi-system pathophysiology with limited therapeutic options. Progress in developing effective therapeutics is constrained by the inadequacy of experimental models to fully recapitulate the multifactorial nature of the disease. Recent evidence underscores the significant involvement of inflammatory, oxidative, and mitochondrial pathways in the pathogenesis of HFpEF, with non-coding RNAs and epigenetic regulation serving as crucial modulators and prospective therapeutic targets. This review maps the HFpEF target landscape, while critically assessing the mechanistic contributions, translational fidelity, and limitations of existing in vivo and in vitro models. Further, advances are noted among the in vitro technologies, including human cardiac organoids and engineered heart tissues integrated with high-throughput multi-omics and computational modeling, enabling in-depth examination of HFpEF mechanisms. Finally, we underscore the necessity of integrative, systems-level approaches and multi-marker strategies to enhance translational relevance, improve risk stratification, and accelerate development of mechanism-based therapies. Collectively, this review supports phenotypic-guided and mechanism-informed therapeutic development for HFpEF, and provides a roadmap for next generation model development and therapeutic innovation.

Humans

Comparison of wall motion and regional ejection fraction at rest and during isometric exercise: concise communication.

The detection of regional abnormalities of left-ventricular wall motion provides strong evidence for the presence of coronary heart disease. In 129 patients undergoing coronary arteriography, the relative value of radionuclide angiographic assessment of wall motion was compared with computer-generated regional ejection fraction, at rest and during handgrip exercise. Wall motion was determined by superposition of computer-derived end-diastolic and end-systolic perimeters. Relative regional ejection fraction was determined using a computer-generated 16-color isocount image that permitted a quantitative assessment of zonal contribution to ejection fraction. Of the 129 patients, coronary arteries were normal in 31 and diseased in 98. Of 24 patients with single-vessel disease, wall-motion abnormalities were present, at rest or during exercise in 15, whereas regional ejection fraction detected 20 patients. Seventy-four patients had multivessel disease. Of these, wall-motion abnormalities occurred in 52 but regional ejection fraction was abnormal in 69 (p less than .01). Overall, sensitivity was 67% by wall motion and 91% by relative regional ejection fraction (p less than .001). Specificity was 94% by wall motion and 87% by regional ejection fraction (not significant). Thus, radionuclide angiographic assessment of regional ejection fraction during handgrip exercise is both highly sensitive and specific for coronary heart disease and significantly enhances detection of coronary heart disease compared with wall-motion assessment, with little loss in specificity.

Cardiac Output

[Determination of cardiac output and ejection fraction using radionuclide angiography. A comparsion with conventional diagnostic methods in cardiology (author's transl)].

Cardiac output and ejection fraction of left and right ventricle were determined in 75 patients with different heart diseases applying a newly developed method which combines radionuclide angiography and triggered blood pool scintigraphy. The comparison of cardiac output and ejection fraction as determined by dye-dilution or thermodilution technique and left ventricular angiography is excellent (coefficient of correlation r equal to 0.86 and r equal to 0.91). Cardiac output and ejection fraction can be determined with this method in single non-invasive operation, i.e. under physiological conditions. The ejection fractions can be determined with high statistical accuracy from time-activity curves of both ventricles. Similar to cine-angiography it is possible to evaluate the ventricular volume, the regional contraction patterns and aneurysmata. Outpatients can be investigated in 30 min. Since the radiation dose in comparison to cine-angiography is very low, this investigation can be repeated several times without harm to the patient. There are no risks as described for cardiac catheterization and contrast angiography. Patients with low cardiac output and ejection fraction can be classified as "high risk patients". In these patients cardiac catheterization can be avoided by applying the described method.

Cardiac Output

[Infleunce of heart cycle length on left ventricular ejection fraction in normals and patients with coronary artery disease].

The ejection fraction is a clinically valuable index of left ventricular pump function. We investigated the influence of a change in heart cycle length in normals (gr. I) and in patients with coronary artery disease without (gr. IIa) and after myocardial infarction (gr. IIb) (atrial pacing 80 and 120 min-1). In all subjects ejection time decreased by ca. 17%. There was no statistical difference between the groups. Ejection fraction (mean absolute values): gr. I (n = 7): - 3.4% (n. s.), gr. IIa (n = 8): - 8.4% (p is less than 0.01), gr. IIb (n = 12): - 6.5% (p is less than 0.01), Gr. IIa + IIb: - 7.2% (p is less than 0.001), gr. I +IIA + IIb: - 6.1% (p is less than 0.001). Compared to the control value the relative decrease for all subjects was -12.3 +/- 12.0% (n = 27). When left ventricular performance is evaluated by ejection fraction using invasive and noninvasive methods (contrast medium ventriculography, echocardiography and scintigraphy) heart cycle length has to be taken into account. The data cannot be normalized by a simple mathematical procedure.

Cardiac Output

Effects of noise on the determination of ejection fraction from left ventricular time-activity curves.

The effects of Poisson noise on three estimates of ejection fraction made from left-ventricular time-activity curves have been investigated. All three methods are based on a sinusoidal model of left-ventricular volume changes. The first, developed by Schelbert et al., overestimates the ejection fraction for low-activity levels and low ejection fractions. The second estimate, which is merely a first-order correction for the contribution of Poisson noise to the first estimate, appears to be more accurate when both estimators are applied to simulated time-activity curves, and the resulting ejection fractions are compared. A third, "maximum likelihood" estimator, when applied to the same data, is apparently more accurate than the first two.

Heart Function Tests