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Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction.

The impact of hypertension on left ventricular (LV) structure, pump function, and heart failure in Dahl salt-sensitive rats is poorly characterized but hypothesized to yield insights into the pathophysiology of heart failure with normal or preserved ejection fraction. Eighty Dahl salt-sensitive rats were fed either a high-salt (HS) or low-salt (LS, controls) diet starting at age 7 weeks. Ventricular properties were measured by echocardiography, hemodynamics and end-systolic and end-diastolic pressure-volume relationships (ESPVR and EDPVR, respectively). Compared with LS controls, HS rats developed severe hypertension and LV hypertrophy. At week 12, HS rats developed passive diastolic dysfunction (leftward/upward shifted EDPVR, increased chamber stiffness) with reductions in end-diastolic volume. However, the ESPVR also shifted upward (enhanced end-systolic function) so that overall pump function was enhanced compared with LS, and there was no change in end-diastolic pressure (EDP). At 16 and 20 weeks, HS hearts enlarged so that end-diastolic volumes and EDPVRs became similar to the respective age-matched LS controls. Concomitantly, the ESPVRs and overall pump function curves also moved toward controls, and ejection fraction declined. Despite normal or enhanced overall pump function at these times, EDP and wet lung weight increased, indicative of development of heart failure. In the Dahl salt-sensitive rat, which pathophysiologically retains salt and water, the development of heart failure (increased EDP and wet lung weight) is dissociated from changes in passive diastolic and active systolic properties. These observations suggest that a volume overload sate plays an important pathophysiological role in development of heart failure despite preserved overall ventricular pump function in this model of chronic hypertension.

Animals↗

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗

"Abnormal" responses of ejection fraction to exercise, in healthy subjects, caused by region-of-interest selection.

We performed serial exercise equilibrium radionuclide angiography in eight normal subjects with each subject executing three tests: control, after nitroglycerin, and after propranolol. The left-ventricular ejection fraction (EF) was calculated by two methods: (a) fixed region-of-interest (FROI) using a single end-diastolic ROI, and (b) variable region-of-interest (VROI) where an end-diastolic and end-systolic region of interest were used. Abnormal maximal EF responses occurred in five of eight subjects during control using FROI but in zero of eight employing VROI (p < 0.05). After nitroglycerin, three of eight subjects had abnormal responses by FROI, but zero of eight were abnormal by VROI (p < 0.05). After propranolol, blunted EF responses occurred in three of seven by both methods. Falsely abnormal EF responses to execrise RNA may occur due to the method of region-of-interest selection in normal subjects with normal or high ejection fractions.

Adult↗

Computer-enhanced digital angiography: correlation of clinical assessment of left ventricular ejection fraction and regional wall motion.

We compared computer-enhanced digital angiography (CEDA) following pulmonary injection of 20 ml Renografin-76 (5 ml/sec) to conventional directly injected left ventriculography (LV) in 13 patients undergoing routine diagnostic catheterization. Left ventricular ejection fraction (LVEF) was determined by planimetry from end-diastolic and end-systolic images by two independent angiographers. The correlation coefficient for LVEF (CEDA vs. LV) was r = 0.75 (p less than 0.005) for observer 1 and r = 0.85 (p less than 0.0005) for observer 2. The interobserver variability for LVEF was very low, resulting in a high correlation coefficient (r = 0.91, p less than 0.0005). Three angiographers independently reviewed both the conventional and CEDA images in a random order for assessment of anterior, apical, and inferior regional wall motion, using a 6-point subjective grading system (198 determinations). The interobserver correlation for subjective assessment of regional wall motion by both LV and CEDA was poor (49% for LV and 59% for CEDA, p = NS). These poor correlations were not improved by excluding any region or angiographer from the analysis. The agreement of regional motion assessments between the two techniques was only 40%. To improve reproducibility of wall motion interpretation, an automated analysis program was developed. First the range of normal contraction was defined from pooled literature data. The movement of any segment of the left ventricular wall could then be determined in millimeters and referenced to the normal range. This method eliminated interobserver variability. In the absence of an acceptable standard of segmental wall motion to which this measurement can be compared, the accuracy of this objective format could not be determined. We conclude that CEDA images allow accurate determination of ejection fraction and that the large interobserver variability of subjective regional wall motion analysis can be overcome by employing more objective formats.

Adult↗

Diagnostic value of body surface map in myocardial infarction: assessment of location, size and ejection fraction as compared with coronary cineangiography and 201Tl myocardial scintigraphy.

The diagnosis of the location and size of old myocardial infarction was made by the map and various indices obtained from the map were correlated with coronary arteriography, left ventriculography, and 201Tl myocardial scintigraphy. Diseased coronary arteries were presumed from Q30, Q40 area and/or peak voltage map and left ventricular wall motion was estimated from subtraction map. There were significant correlations between ejection fraction and sigma R in anterolateral MI (r = 0.51, p less than 0.001) and between ejection fraction and nQ30 in anterolateral (r = -0.47, p less than 0.001) and inferoposterior (r = -0.63, p less than 0.01) MI. Negative correlation was observed between myocardial uptake ratio (MUR) and nQ30 (r = -0.69, p less than 0.001) and positive correlation between MUR and sigma R (r = 0.50 p less than 0.01) in anterolateral MI. Those cases which could not be diagnosed by either ECG or 201Tl scintigraphy were correctly diagnosed by the map and it proved to have an excellent diagnostic accuracy for myocardial infarction.

Adult↗

Automated calculation of gallbladder ejection fraction.

We have developed a computer method which by automatically locating the border of the gallbladder in each image and subtracting a varying location-dependent background corresponding to the gallbladder border overcomes the difficulties associated with quantitating gallbladder contraction. These difficulties are attributable to significant and changing background activity, imprecise manual delineation of the gallbladder, and the changing position and shape of the gallbladder. Validation studies using a gallbladder phantom showed the method to be very accurate. No significant difference (P greater than 0.05) was observed between the expected and calculated ejection fractions. Ten patient studies were analyzed, with a resulting range of gallbladder ejection fractions of 22-79%. Excellent reproducibility was obtained with an average intraobserver coefficient of variation of 3.5%, and no statistically significant difference in interobserver measurements (P greater than 0.05). The regression line for interobserver measurements had a slope of 0.96 +/- 0.08, an intercept of 1.6 +/- 4.0%, and a correlation coefficient of 0.99. From these preliminary results we conclude that this method offers a reliable means of quantitating gallbladder contraction.

Cholecystokinin↗

[The determination of the ejection fraction of the left ventricle by the first passage of an indicator bolus. Comparison of two curve-fitting algorithms (author's transl)].

In 28 studies of the first left ventricular bolus passage, the end-systolic and end-diastolic phase were determined in the left ventricular time activity curve (4 msec per frame) by simply smoothing this curve 25 times. Comparing this method with a highly sophisticated curve-fitting algorithm (Sinusoidial Approximation), a very high correlation (r = 0.95) was found of the resulting ejection fractions. Thus, the two methods can be regarded as equivalent. In comparison with the ejection fractions evaluated by cineventriculoangiographic studies, a good correlation (r = 0.85) was obtained as well. To generate end-systolic and end-diastolic frames the two frames containing the highest left ventricular radioactivity were designated as end-diastolic, and the two frames containing the lowest radioactivity as end-systolic, for each heart cycle. This criterion was found to be very efficient although the temporal resolution was 8 msec per image. Furthermore, mean filling- and ejection-times of the left ventricle were derived from the extensively smoothed time activity curve. Those parameters seemed not to be of great clinical value. By employment of fast computing procedures, the evaluation time of a first passage (including image and curve generation) could be reduced to less than 10 min. Accuracy remained constant so that this method was introduced into our clinical routine diagnostics.

Cardiac Output↗

The effect of midazolam on left ventricular pump performance and contractility in anesthetized patients with coronary artery disease: effect of preoperative ejection fraction.

Forty patients undergoing coronary artery bypass grafting were studied, of whom 24 had depressed global left ventricular (LV) function at preoperative catheterization, to evaluate the effects of midazolam on LV pump performance and contractility. Transesophageal echocardiography and simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% O2 and after 0.1 mg/kg of midazolam. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to estimate LV contractility. In the entire study population, midazolam did not affect cardiac index. Heart rate and mean arterial pressure were reduced (63 +/- 13 to 59 +/- 12 bm; P < 0.0006 and 89 +/- 15 to 76 +/- 16 mm Hg; P < 0.0001) as were pulmonary capillary wedge pressure, central venous pressure, and systemic and pulmonary vascular resistance. Afterload, as measured by end-systolic stress, was reduced (55 +/- 33 to 48 +/- 26 kdyne/cm2; P = 0.007) with no change in fractional shortening or percent area change. As a result, systolic function decreased in relation to observed end-systolic stress, providing evidence of reduced LV contractility. Thus, midazolam administration (0.1 mg/kg) caused no change in cardiac pump performance but decreased LV contractility in the entire population. Myocardial contractility was lower at baseline and after the administration of midazolam in the depressed ejection fraction group, but the decrease in contractility was not exaggerated in the depressed ejection fraction group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Impact of infarct location on left ventricular ejection fraction after correction for enzymatic infarct size in acute myocardial infarction treated with primary coronary intervention.

BACKGROUND: Left ventricular function and infarct size are strong predictors for prognosis after acute myocardial infarction (MI). Anterior MI is associated with greater reduction of left ventricular ejection fraction (LVEF) and worse prognosis. Our objective was to study whether the impact of infarct size on global LVEF is dependent of infarct location. METHODS: We analyzed 888 patients treated with primary percutaneous coronary intervention for acute MI. Enzymatic infarct size and LVEF within 1 week were measured. In 490 patients (55%), LVEF was measured a second time at 6 months. RESULTS: Every 1000 U/L of cumulative lactate dehydrogense release corresponded to a decrease of 4.7% (95% CI 4.1-5.3) in LVEF measured within 1 week post MI for left anterior descending coronary artery (LAD)-related infarcts and to a decrease of 2.4% (95% CI 1.7-3.1) in LVEF measured within 1 week post MI for non-LAD-related infarcts (P < .0001). Left ventricular ejection fraction measured 6 months post MI showed a decrease for every 1000 U/L cumulative lactate dehydrogense release of 4.8% (95% CI 4.2-5.3) for LAD and 2.4% (95% CI 1.7-3.1) for non-LAD-related infarcts (P < .0001). Multivariate correction for relevant clinical and angiographic data did not change these results. CONCLUSION: In patients with a first acute MI treated with primary percutaneous coronary intervention, LAD-related infarcts show for a similar amount of myocardial necrosis as determined by enzymatic infarct size, a lower residual LVEF when compared with non-LAD-related infarcts.

Angioplasty, Balloon, Coronary↗

The effect of incremental positive end-expiratory pressure on right ventricular hemodynamics and ejection fraction.

The effects of incremental positive end-expiratory pressure (PEEP) on right ventricular (RV) function were evaluated in 36 (n = 36) ventilated patients. Positive end-expiratory pressure was increased from 0 (baseline) to 20 cm H2O in 5-cm H2O increments and RV hemodynamics and thermally derived right ventricular ejection fraction (RVEF), right ventricular end-diastolic volume index (RVEDVI), and right ventricular end-systolic volume index (RVESVI) were computed. Right ventricular contractility was determined from the analysis of RV systolic pressure-volume relations. Right ventricular ejection fraction declined from 42 +/- 8% at baseline to 30 +/- 9% at 20 cm H2O PEEP. Right ventricular end-diastolic volume index declined between 0 and 5 cm H2O PEEP (103 +/- 42 to 92 +/- 34 ml.m-2) and then increased to 113 +/- 40 at 20 cm H2O PEEP. Right ventricular end-systolic volume index increased from 60 +/- 31 ml.m-2 at baseline to 79 +/- 34 ml.m-2 at 20 cm H2O PEEP. The slope (E) of the relation of RV peak systolic pressure to RV end-systolic volume index decreased from 0.26 mm Hg.m2.ml-1 between PEEP of 0-15 cm H2O to 0.05 mm Hg.m2.m-1 at PEEP greater than 15 cm H2O. It is concluded that low levels of PEEP have a predominant preload reducing effect on the RV. Above 15 cm H2O PEEP, RV volumes increase and E decreases, consistent with increased RV afterload and a decline in RV contractility.

Adult↗

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: validation of an elastic surface model approach in comparison to cardiac magnetic resonance imaging, 4D-MSPECT and QGS.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Adult↗

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.

BACKGROUND: Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. METHODS: Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. RESULTS: There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). CONCLUSIONS: The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.

Blood Pressure↗

Left ventricular end-diastolic volume from ejection fraction and stroke volume in pigs during IVC occlusion.

BACKGROUND: Real-time measurement of left ventricular end-diastolic volume (LVEDV), combined with left ventricular end-diastolic pressure (LVEDP), would allow continuous measurement of intraoperative diastolic function. In pursuit of this goal, we examined stroke volume divided by ejection fraction for calculation of LVEDV(sv/ef). METHODS: Five anesthetized pigs underwent median sternotomy and pericardiotomy. A transit-time ultrasonic flow probe on the ascending aorta provided cardiac output. A micromanometer provided LV end-diastolic pressure. End-diastolic and end-systolic areas were measured from LV short-axis cross sections to obtain ejection fraction. LVEDV(sv/ef) was calculated during IVC occlusion. Steady-state LVEDV(echo) was determined using a three-plane echocardiography model. LVEDV(echo) was used to validate steady-state LVEDA in each experiment. RESULTS: Correlation coefficients for linear and pressure-volume relation analyses ranged from 0.46 to 0.99. The two methods for measuring LVEDV generated compliance curves with an overall reliability coefficient of 0.84. CONCLUSIONS: The LVEDV(sv/ef) method may facilitate real-time determination of LV compliance.

Animals↗

[A new radioisotopic method of studying local ejection fractions. Application to the study of abnormalities of left ventricular contraction].

The authors describe a new method of segmental analysis of the left ventricle by equilibrium gamma cinecardiography. The left ventricle in the left anterior oblique projection was divided into 16 triangular sectors with reference to the centre of gravity of the radioactivity of the end diastolic frame. The following parameters were calculated for each sector (the spatial equivalent of a quarter of an orange): end diastolic, end systolic and ejection activity and the regional ejection fraction. The percentage of normal and asynergic regions was deduced. The end diastolic activity of regions with ejection fractions of over 0,47 was compared to the total end diastolic activity to obtain the percentages. This method of segmental division has the advantages of being completely automatic, based entirely on an objective reference calculated by computer and of giving very reproductible quantitative results. The clinical applications in a series of I400 patients examined by this method were numerous (the detection of dyskinesia in acute myocardial infarction). It was particularly useful in chronological and follow-up studies (exercise scintigraphy before and after glyceryl trinitrite).

Cardiac Output↗

A comparison of two radionuclide ejection-fraction techniques with contrast angiography in ischemic heart disease and valvular heart disease.

First-pass radionuclide angiography (FPRA) in the 30 degree right anterior oblique and equilibrium gated radionuclide angiography (EGNA) in the 45 degree left anterior oblique were used for quantitative measurements of left ventricular ejection fraction (LVEF). Equipment used was a 400T gamma-camera interfaced with a Simis III Informatek computer. The results were compared with contrast angiography (CA). The aim of this study was to determine the sensitivity of both radionuclide techniques. The present data are based on 65 patients in whom CA and EGNA were performed. In 47 patients both FPRA and EGNA were performed. Results suggested that in ischemic heart disease (IHD) and valvular heart disease (VHD) the EGNA technique is well correlated with CA (r = 0.9 and 0.73, respectively). FPRA correlated well only with CA in IHD (r = 0.86), but not in VHD (r = 0.18). This study indicates that both FPRA and EGNA are sensitive, noninvasive techniques for measuring ejection fraction in IHD, while in VHD, EGNA is more sensitive technique than FPRA.

Adolescent↗

A randomized trial of coronary artery bypass surgery. Survival of patients with a low ejection fraction.

The Coronary Artery Surgery Study (CASS) was designed to compare medical and surgical treatment of selected patients with chronic, stable coronary artery disease. This report concerns a subset of patients with reduced ventricular function. Of 780 patients randomly assigned to medical or surgical treatment, 160 had ejection fractions above 0.34 but below 0.50 at base line and have been followed for an average of seven years. Eighty-two patients were assigned to medical therapy, and 78 to surgery; the two groups were comparable at base line with regard to prognostically important variables. At seven years, 84 per cent of patients in the surgical group were alive, as compared with 70 per cent of the medical group (P = 0.01). Nearly half the patients with impaired ventricular function had triple-vessel disease at entry; at seven years, observed survival in this group was 88 and 65 per cent for those assigned to surgical and medical treatment, respectively (P = 0.009). Survival of patients with single-vessel or double-vessel disease was similar in the two treatment groups. We conclude that patients with triple-vessel disease and ejection fractions higher than 0.34 but lower than 0.50 appear to have improved seven-year survival with elective bypass surgery.

Cardiac Output↗

Left ventricular volumes, ejection fraction, and regional wall motion calculated with gated technetium-99m tetrofosmin SPECT in reperfused acute myocardial infarction at super-acute phase: comparison with left ventriculography.

BACKGROUND: Noninvasive assessment of acute myocardial infarction (AMI) requires information about both myocardial perfusion and left ventricular (LV) function. The automated quantification of electrocardiographic-gated myocardial scintigraphy with technetium-99m tetrofosmin (QGS) can provide this information. METHODS AND RESULTS: Coronary arteriography, QGS, and left ventriculography (LVG) were performed in 229 patients with reperfused AMI within 2 days after onset. All infarcted vascular territories (229 segments) were visualized with scintigraphic perfusion images. The mean wall motion score (WMS) was 15.9+/-2.8 by means of QGS and 16.3+/-2.9 by means of LVG. The correlation between WMS obtained by means of QGS and that obtained by means of LVG was close (y = 0.913x + 1.016, r = 0.94, P<.001), but that obtained by means of QGS was significantly lower than that obtained by means of LVG (P<.0001). Total agreement for the assessment of regional wall motion reached 75 % (kappa, 0.66). Although the LV values obtained by means of QGS and LVG correlated well (end-diastolic volume, r = 0.67, P<.0001; end-systolic volume, r = 0.79, P<.0001; ejection fraction, r = 0.78, P<.0001), end-diastolic volume and ejection fraction tended to be underestimated with QGS. CONCLUSION: QGS data were considered to be useful in detecting infarcted vascular territory and LV function, even in AMI, within 2 days after onset.

Adult↗

Determination of right ventricular ejection fraction in children with cystic fibrosis.

The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO2, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung disease was sometimes associated with normal right heart contractility.

Adolescent↗