Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether higher left ventricular inotropic reserve, defined as the increase in left ventricular ejection fraction (LVEF) in response to intravenous dobutamine infusion, or other ventriculographic variables predict the increase in LVEF after beta-blocker therapy in patients with nonischemic cardiomyopathy (NICM). BACKGROUND: Long-term beta-blocker therapy increases LVEF in some patients with NICM. Other than dose, there are no definite predictors of LVEF increase. METHODS: Thirty patients with LVEF < or = 0.35 and NICM underwent assessment of LVEF at rest and after a 10-min intravenous infusion of dobutamine at 10 microg/kg/min, using equilibrium radionuclide ventriculography. Age was 49 +/- 11 years, 33% women, functional class 2.6 +/- 0.5, duration of chronic heart failure 3.2 +/- 2.9 years, LVEF 0.21 +/- 0.07, left ventricular end-diastolic volume index 180 +/- 64 ml/m2. Right ventricular ejection fraction (RVEF) was abnormal in 37%. Mean dobutamine-induced augmentation of LVEF (DoALVEF) was 0.12 +/- 0.08. Patients were started on one of three beta-blockers (carvedilol, bucindolol or metoprolol) and the dose was advanced to the maximum tolerated. RESULTS: Left ventricular ejection fraction, reassessed 7.4 +/- 5.9 months after maximum beta-blocker dose was reached, increased to 0.34 +/- 0.13 (p = 0.0006). The following baseline variables correlated with improvement of LVEF: DoALVEF (p = 0.001), RVEF (p = 0.005), systolic blood pressure at end of dobutamine infusion (p = 0.02) and dose of beta-blocker (p = 0.07). In a multivariate analysis, only DoALVEF (p = 0.0003) and RVEF (p = 0.002) were predictive of the increase in LVEF. CONCLUSIONS: Patients with nonischemic cardiomyopathy who have higher left ventricular inotropic reserve and normal RVEF derive higher increase in LVEF from beta-blocker therapy.

Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients.

Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol. kg(-1). min(-1)) under either hypoglycemic (approximately 2.8 mmol/l) or euglycemic (approximately 5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects (n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (DeltaLVEF = 11 +/- 2%) and PFR [DeltaPFR = 0.88 +/- 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (DeltaLVEF = 13 +/- 2%; DeltaPFR = 0.79 +/- 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (DeltaLVEF = 7 +/- 1%) and nondiabetic (DeltaLVEF = 4 +/- 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study (P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.

Selective use of single-photon emission computed tomography myocardial perfusion imaging in a chest pain center.

Emergency department chest pain centers (CPCs) vary in their approach to patients with chest pain and nonischemic electrocardiograms (ECG). Although single-photon emission computed tomography (SPECT) myocardial perfusion imaging has been evaluated in this setting, both acutely at rest and after stress, we questioned its application in all patients. We prospectively evaluated the utility of selective SPECT imaging in a CPC (i.e., rest SPECT for ongoing pain, stress SPECT if unable to undergo exercise electrocardiography) and its impact on the overall disposition of all emergency department chest pain patients. Over 3 years, 2,601 patients were evaluated in a CPC (2,211 [85%] were sent home, 390 [15%] were hospitalized). Of 390 CPC patients hospitalized, 182 (47%) were diagnosed with coronary artery disease at the time of hospital discharge. Only 28 patients (1.1%) had an acute myocardial infarction. After 3 years, the proportion of all chest pain patients hospitalized and those diagnosed as "rule-out myocardial infarction" decreased from 53% to 41% and 32% to 18% of all chest pain patients, respectively (both p <0.0001). Overall, 906 patients (35%) required SPECT imaging to complete the CPC evaluation. Had SPECT imaging not been performed selectively, and all 906 patients been admitted, 762 (29%) would have been hospitalized unnecessarily based on the final diagnoses. Alternatively, sending all these patients home would have resulted in 144 (6%) inappropriate discharges of patients with coronary artery disease. A CPC protocol using the selective use of SPECT imaging permits the complete evaluation of all patients in the CPC, significantly reduces hospitalizations for chest pain, and restricts hospital admission to more appropriate patients.

Dobutamine-induced augmentation of left ventricular ejection fraction predicts survival of heart failure patients with severe non-ischaemic cardiomyopathy.

AIMS: The prognosis of patients with severe non-ischaemic dilated cardiomyopathy is variable. The predictive value of currently utilized tests is suboptimal. The purpose of this study was to determine the prognostic value of dobutamine-induced augmentation of left ventricular ejection fraction in patients with non-ischaemic dilated cardiomyopathy. METHODS AND RESULTS: Sixty-two patients with left ventricular ejection fraction < or =0.30 underwent exercise testing with gas exchange analysis and assessment of left ventricular ejection fraction at rest and after a 10-min intravenous infusion of dobutamine at 10 microg x kg(-1) x min(-1), using equilibrium radionuclide ventriculography. Age was 48+/-11 years, 32% females, functional class 2.6+/-0.6, resting left ventricular ejection fraction 0.20+/-0.06, and peak exercise oxygen consumption (mVO2) 19+/-6 ml x kg(-1) x min(-1). Mean dobutamine-induced augmentation of left ventricular ejection fraction (DeltaLVEF) was 0.09+/-0.06 (median 0.08, range -0.03 to 0.26). Follow-up was 25+/-15 months during which there were 12 deaths and five transplantations. Patients were divided into two groups based on median DeltaLVEF. The transplant-free survival was better in the group with higher DeltaLVEF (94% vs 64%, P<0.008). In multivariate analysis incorporating age, gender, duration of chronic heart failure, functional class, right and left ventricular ejection fraction, DeltaLVEF, left ventricular end-diastolic volume index, and mVO2, only DeltaLVEF was predictive of 1-year, 3-year, and overall transplant-free survival (RR 0.09, 0.03, and 0.13;P 0.03, 0.09, and 0.08 respectively). The linear correlation between DeltaLVEF and mVO2(r=0.3) and between DeltaLVEF and left ventricular ejection fraction (r=0.5) was weak. CONCLUSION: Dobutamine-induced augmentation of left ventricular ejection fraction is a strong prognostic variable, independent of exercise capacity and resting ventriculographic variables, in severe non-ischaemic systolic dysfunctional heart failure.

Effect of left ventricular volume on results of coronary artery bypass grafting.

After coronary artery bypass grafting, our patients with ischemic cardiomyopathy and significant left ventricular (LV) dilation demonstrated an improvement in angina symptoms, acceptable operative and medium-term survival, a trend toward improvement in LV ejection fraction, and a significant reduction in LV chamber size. Our results suggest that patients with ischemic cardiomyopathy and LV dilation should not be excluded from surgical revascularization based on ventricular size alone.

Assessment of left ventricular ejection fraction with quantitative gated SPECT: accuracy and correlation with first-pass radionuclide angiography.

BACKGROUND: Quantitative gated single photon emission computed tomography (SPECT [QGS]) software is widely used for the assessment of left ventricular ejection fraction (LVEF). Potentially confounding variables that may affect the accuracy of quantitative analysis of LVEF remain undefined. This study evaluated the accuracy of QGS as a means of determining LVEF in a wide range of LVEF values; evaluated the effect of extracardiac activity, count statistics, heart size, and perfusion defects on the accuracy of QGS LVEF; and compared QGS LVEF obtained at rest with that obtained after stress. METHODS AND RESULTS: QGS-derived LVEF was compared with rest first-pass radionuclide angiography (FPRNA) LVEF in 400 electrocardiographic-gated SPECT studies. The overall correlation between QGS and FPRNA LVEF was only fair (r = 0.66, SEE = 11.85%). In 35 of the patient studies (9%) with high extracardiac activity, the automated software failed, and no correlation was obtained. In the remaining 365 patient studies (91%), left ventricular contours were successfully identified. In these studies, correlation was better (r = 0.74, SEE = 9.77%). Agreement was better for images with high counts (r = 0.81, SEE = 8.66%) than for images with low counts (r = 0.61, SEE = 11.17%). Patient studies with abnormal LVEF had better correlation (r = 0.77, SEE = 6.4%) than studies with normal LVEF (r = 0.46, SEE = 10.2%). Agreement between QGS LVEF and FPRNA LVEF was better in hearts with large end diastolic volumes (>104 mL) than in hearts with small volumes. Overall, mean QGS LVEF was lower than mean FPRNA LVEF (54%+/-14% vs. 58%+/-14%, P<.0001). There was no difference between mean rest and stress QGS LVEF in the same patients, even in patients with stress-induced ischemia. CONCLUSIONS: QGS is a valuable method for assessing resting LVEF. However, QGS LVEF is often lower than FPRNA LVEF. Accuracy is affected by high extracardiac activity, low count density, and small size of the left ventricle.

Association of patients' perception of health status and exercise electrocardiogram, myocardial perfusion imaging, and ventricular function measures.

BACKGROUND: Patients' viewpoint of their health status is increasingly used as an important outcome measure of the success of treatments. Because clinicians rarely formally measure patients' health-related quality of life, the question arises whether noninvasive testing for ischemia can provide similar information regarding physical functioning and general health perception. METHODS: We measured physical functioning and general health status with the Medical Outcomes Study Short Form (SF-36) survey in 195 consecutive patients (68% male, mean age 55.6 +/- 11.1 years) referred for exercise testing with myocardial perfusion imaging. The survey was completed immediately before the exercise test. RESULTS: In the multivariate analysis, the strongest predictor of physical functioning and general health perception was metabolic equivalents. However, the best model, including demographic, clinical, and test variables, predicted only 14% of the variation in physical functioning and 10% of the variability in general health perception. CONCLUSIONS: The variation in physical functioning and general health perception, as measured by the SF-36, among patients referred for exercise testing is not predicted well by the results of the test. As expected, several test results are significantly associated with physical functioning and general health perception; however, there was substantial overlap among individual patients, suggesting that the parameters are poor surrogates for the actual assessment of the domains. If these domains are deemed important to tracking patient outcomes, then they should supplement the current assessments of these patients.

Validation of the Yale circumferential quantification method using 201Tl and 99mTc: a phantom study.

UNLABELLED: The Yale circumferential quantification (Yale CQ) method for quantification of SPECT images has been validated previously using empirically derived correction factors. In the present studies, the Yale CQ method was further validated using 2 SPECT gamma cameras and 2 radioisotopes. METHODS: SPECT images were acquired from cardiac phantoms with multiple fillable inserts to simulate myocardial perfusion defects of varying extents and severities. Seventy phantom configurations were created. One hundred and forty SPECT images (70 with 99mTc and 70 with 201TI) were acquired using a triple-head SPECT camera. SPECT defects were quantified using the Yale CQ method, with incorporation of 99mTc- and 201TI-derived normal databases and correction factors. RESULTS: Quantified phantom SPECT defect sizes acquired with 99mTc correlated well with actual calculated defect sizes (r = 0.96, y = 0.92x - 0.41). Bland-Altman analysis of agreement revealed strong agreement over a wide range of defect sizes, with a mean error of 1.2% and 2 SDs of 5.0%. Overall 201TI SPECT defect sizes also correlated well with actual defect sizes (r = 0.92), but there was a systematic underestimation (y = 0.72x - 0.76). Bland-Altman analysis showed underestimation over the entire range of defect sizes, with a mean error of 3.4% and 2 SDs of 7.5%. Implementation of a normal 201TI phantom database improved accuracy of quantification (r = 0.95, y = 0.87x - 1.36). The addition of 201TI-specific correction factors further improved accuracy (r= 0.94, y = 0.98x - 1.52). Reproducibility of SPECT defect sizes quantification for 99mTc using 2 gamma cameras was excellent (r = 0.98, y = 0.98x + 0.84). CONCLUSION: The Yale CQ SPECT quantification method, using the empirically derived correction factors, provides accurate and reproducible quantification of phantom defects over a wide range of defect sizes. Accurate quantification of 201TI and 99mTc SPECT defect sizes requires radiotracer-specific normal databases.

Reproducibility and accuracy of gated SPECT for determination of left ventricular volumes and ejection fraction: experimental validation using MRI.

UNLABELLED: Quantitative gated SPECT (QGS) has been used for computation of left ventricular volumes and ejection fraction. This study evaluated, first, the effect of injected dose, time of imaging, and background activity on the reproducibility of QGS and, second, the accuracy of QGS, compared with cine MRI, for determining left ventricular volumes and ejection fractions in dogs with and without perfusion defects. METHODS: Sixteen dogs were subjected to either chronic occlusion of the circumflex artery (group I, no perfusion defect) or acute occlusion of the anterior descending coronary artery (group II, perfusion defect). Both groups underwent serial MRI and SPECT. RESULTS: ( QGS was very reproducible using the automated program (r = 0.99997). Correlation between left ventricular ejection fraction (LVEF) at 15 and 45 min was poor after the low-dose injection (r = 0.54; SE = 9%) and only fair after the high-dose injection (r = 0.77; SE = 5%). Correlation was poor in the presence of significant background activity (r = 0.36; SE = 12%). Correlation between QGS left ventricular volumes and MRI was good for group I (end-diastolic volume, r = 0.86; end-systolic volume, r = 0.81) and only fair for group II (end-diastolic volume, r = 0.66; end-systolic volume, r = 0.69). The overall LVEF correlation between QGS and MRI was poor (r = 0.51). QGS LVEF (mean +/- SD, 42% +/- 3%) overestimated MRI LVEF (29% +/- 2%). CONCLUSION: QGS provides a highly reproducible estimate of LVEF. However, QGS is affected by changes in background activity, time of imaging, and injected dose. In the presence of perfusion defects, QGS overestimated volume relative to MRI. The correlation between QGS- and MRI-derived LVEF was poor in this canine model.

The role of radionuclide imaging in the triage of patients with chest pain in the emergency department.

The triage of patients presenting to the emergency department with chest pain and a normal or nondiagnostic ECG poses a significant diagnostic challenge to emergency physicians and cardiologists, leading to unnecessary hospital admissions and substantial associated costs. Radionuclide myocardial perfusion imaging can potentially play an important role in this setting, by providing both a safe and efficient means to risk stratify patients with a low-to-moderate likelihood of unstable angina. The proposed algorithm may serve as a strategy to improve utilization of hospital resources while safely identifying the subgroup of patients with acute chest discomfort who do not need to be admitted to the hospital.

An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial.

STUDY OBJECTIVE: Conventional emergency department testing strategies for patients with chest pain often do not provide unequivocal diagnosis of acute coronary syndromes. This study was conducted to determine whether the routine use of single photon emission computed tomography (SPECT) imaging at rest and early exercise stress testing to assess intermediate-risk patients with chest pain and no ECG evidence of acute ischemia will lead to earlier discharges, more discriminate use of coronary angiography, and an overall reduction in average costs of care with no adverse clinical outcomes. METHODS: All patients in this study had technetium 99m tetrofosmin SPECT imaging at rest and were randomly assigned to either a conventional (results of the imaging test blinded to the physician) or perfusion imaging-guided (results of the imaging test unblinded to the physician) strategy. Patients in the conventional arm were treated at their physician's discretion. Patients in the perfusion imaging-guided arm were treated according to a predefined protocol based on SPECT imaging test results: coronary angiography after a positive scan result and exercise treadmill testing after a negative scan result. Study endpoints consisted of total in-hospital costs and length of stay. Hospital costs were calculated using hospital department-specific Medicare cost/charge ratios. Length of stay was calculated as total hospital room days billed (regular and intensive care). RESULTS: We enrolled 46 patients, 9 with acute myocardial infarctions. Patients randomly assigned to the perfusion imaging-guided arm had $1,843 (95% confidence interval [CI] $431 to $6,171) lower median in-hospital costs and 2.0-day (95% CI 1.0 to 3.0 days) shorter median lengths of stay but similar rates of in-hospital and 30-day follow up events as patients in the conventional arm. CONCLUSION: An ED chest pain diagnostic strategy incorporating acute resting (99m)Tc tetrofosmin SPECT imaging and early exercise stress testing may lead to reduced in-hospital costs and decreased length of stay for patients with acute chest pain and nondiagnostic ECGs.

Quantification of regional myocardial wall thickening on electrocardiogram-gated SPECT imaging.

BACKGROUND: Current assessment of regional left ventricular function with electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT) imaging is generally performed by visual inspection. The objective of this study was to develop and validate a new computer algorithm for quantifying regional left ventricular wall thickening on ECG-gated SPECT images. METHODS: Regional wall thickening was measured from count density changes during the cardiac cycle observed in 24-sector circumferential count distribution profiles generated from each of 8 frames of an ECG-gated SPECT study. Wall thickening was expressed as the percent count increase during systole relative to end diastole. The program was tested in a phantom simulation and in patient studies consisting of a pilot study (n = 40) and a validation study (n = 33). In the phantom study varying degrees of wall thickening were simulated. The pilot study included 20 normal subjects with low likelihood (<3%) of coronary disease and 20 patients with prior myocardial infarction. Mean wall thickening - 2 standard deviations, measured in normal subjects, defined the lower limit of normal wall thickening. This criterion was tested in the validation study in 13 normal subjects and 20 patients with prior myocardial infarction. Abnormal wall thickening was characterized by extent (percent of circumferential profile) and severity (minimal thickening). RESULTS: The phantom study showed excellent linear correlation between wall thickening computed by the new software and actual wall thickening (r = 0.98). Interobserver and intraobserver reproducibility of quantitative assessment of minimal wall thickening were excellent (r = 0.98 and 0.99, P < .001). Regional wall thickening varied considerably from apex to base in the same ventricle among normal subjects. The average lower limit of normal wall thickening was 25% to 30% at the apex, 19% to 24% in the mid-ventricle, and 13% to 20% at the base of the left ventricle. In the validation study 11 of 13 normal subjects had wall thickening profiles within the pre-defined normal range. All 20 patients with prior myocardial infarction had abnormal regional wall thickening. Minimal regional wall thickening in the infarct areas was 5.4% +/- 5.5%, compared with 30.1% +/- 9.1% wall thickening in comparable anatomic areas in normal subjects (P < .001). CONCLUSION: Regional wall thickening can be quantified reliably from regional count density changes during the cardiac cycle on ECG-gated SPECT images. The new software measured the extent and severity of abnormal regional wall thickening relative to normal files. The method is highly reproducible. Clinical validation showed good differentiation between normal subjects and patients with prior infarction. Quantification of regional wall thickening may enhance diagnostic accuracy and reproducibility of interpretation of gated SPECT imaging.

Failure to improve left ventricular function after coronary revascularization for ischemic cardiomyopathy is not associated with worse outcome.

Background-Preoperative identification of viable myocardium in patients with ischemic cardiomyopathy is considered important because CABG can result in recovery of left ventricular (LV) function. However, the hypothesis that lack of improvement of LV function after CABG is associated with poorer patient outcome is untested. Methods and Results-Outcome was compared in patients with ischemic LV dysfunction (LVEF 0.05 increase in LVEF (group A) and 36 (35%) had no significant change, or

Quantification of SPECT myocardial perfusion images: methodology and validation of the Yale-CQ method.

BACKGROUND: Quantification of single photon emission computed tomography (SPECT) images is important for reproducible and accurate image interpretation. In addition, SPECT quantification provides important prognostic information. The purpose of this study was to validate the Yale circumferential quantification (Yale-CQ) method in phantom studies. METHODS: Myocardial perfusion defects of varying extent and severities were simulated in a cardiac phantom with fillable defect inserts. Forty-five different phantom configurations simulated 45 different myocardial perfusion defect sizes, ranging from 1.6% to 32% of the cardiac phantom volume. Automatic processing was compared with manual processing in the phantom SPECT studies. RESULTS: The automatic Yale-CQ algorithm performed well in all phantom studies. Compared with manual processing, the mean absolute error for automatically determined center of short axis slices was 0.27 pixel in the x direction, 0.45 pixel in the y direction, and 0.15 pixel in radius. Quantification of phantom defects with the Yale-CQ method correlated well with actual defect sizes (R = 0.99), but there was a systematic underestimation (mean error = -7.9%). With derived correction factors the overall correlation between 45 phantom defects and actual defect sizes was excellent, and the estimation error was significantly improved (R = 0.98, mean error = -0.82% for manual method and -0.95% for automatic method). CONCLUSION: The automatic processing algorithm performs well for the phantom studies. Myocardial perfusion abnormalities can be quantified accurately by use of the Yale-CQ method. Quantified SPECT defect size can be expressed as a percentage of the left ventricle.

Assessment of cardiac and pulmonary function in adult patients with Hodgkin's disease treated with ABVD or MOPP/ABVD plus adjuvant low-dose mediastinal irradiation.

We evaluated the long-term effects of combined modality therapy (CMT) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) or mechlorethamine, vincristine, prednisone, procarbazine (MOPP)/ABVD plus adjuvant low-dose (< 30 Gy) involved-field radiation therapy (LDRT) on cardiac and pulmonary functions in adult patients with Hodgkin's disease (HD). Adjuvant LDRT (mean dose, 2340 cGy) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD (n = 10) and ABVD (n = 14). The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2, respectively. Cardiac and pulmonary function tests were performed in all patients and, when available, were compared with pretreatment studies. After a median follow-up of 6.3 years, none of the patients had cardiac or pulmonary symptoms. A 4.7% overall decrease in left ventricular ejection fraction (LVEF) was observed (p = 0.03), but only one patient had a mildly decreased LVEF (47%). Diastolic function, LVEF, and left ventricular volume remained within the normal range in the other 23 patients. Mild pulmonary function study abnormalities occurred in 8 of 24 patients, 6 of whom were cigarette smokers. There were no significant changes in total lung capacity and forced vital capacity (FVC) values, but there was a 3% overall decrease in FEV1/FVC ratio (p = 0.05). In adult patients with HD, adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up. Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function.