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Aims The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial 123I- m IBG and 99mTc-tetrofosmin SPECT imaging in heart failure (HF) subjects and to assess the differences between patients with ischaemic and non-ischaemic HF. Methods and results Results of quantitative analyses of 123I-mIBG myocardial SPECT, alone and in combination with 99mTc tetrofosmin SPECT, were studied in 619 ischaemic (I) and 319 non-ischaemic (NI) HF subjects from the ADMIRE-HF trial. Cardiac and all-cause mortality data for 2-year follow-up were collected in the extension study (ADMIRE-HFX) and were examined in relation to extent and severity of voxel-based defects, the number of myocardial segments with significant dysinnervation (derived score ≥2), and 123I-mIBG/99mTc tetrofosmin mismatch quantitation. Cox proportional hazards and survival analyses were used to identify higher and lower risk groups and to define thresholds for optimal discrimination between the two. Two-year all-cause and cardiac mortality were not significantly different between IHF and NIHF subjects. Mortality was higher in patients with dysinnervation involving >50% of the myocardium. Highest cardiac mortality risk for IHF subjects was seen with perfusion defects involving 20–40% of the myocardium. By comparison, NIHF subjects with smaller perfusion abnormalities (

The purpose of this study was to develop and validate new approaches to quantitative MIBG myocardial SPECT imaging in heart failure (HF) subjects. Quantitative MIBG myocardial SPECT analysis methods, alone and in conjunction with 99mTc-tetrofosmin perfusion SPECT, were adapted from previously validated techniques for the analysis of SPECT and PET perfusion imaging. To account for underestimation of MIBG defect severity in subjects with global reduction in uptake, a mixed reference database based on planar heart/mediastinum (H/M) ratio categories was used. Extent and severity of voxel-based defects and number of myocardial segments with significant dysinnervation (derived score ≥2) were determined. MIBG/99mTc-tetrofosmin mismatch was quantified using regions with preserved innervation as the reference for scaling 99mTc-tetrofosmin voxel maps. Quantification techniques were tested on studies of 619 ischemic (I) and 319 non-ischemic (NI) HF subjects. Using all analytical techniques, IHF subjects had significantly greater and more severe MIBG SPECT abnormalities compared with NIHF subjects. Innervation/perfusion mismatches were also larger in IHF subjects. Findings were consistent between voxel- and myocardial-segment-based quantitation methods. Multiple objective methods for quantitation of MIBG SPECT imaging studies provided internally consistent results for distinguishing the different patterns of uptake between IHF and NIHF subjects.

Since atrial fibrillation (AF) impacts the measurement and interpretation of left ventricular ejection fraction (LVEF), we hypothesized that the outcome in heart failure (HF) with AF and LVEF ≤ 35% would be more strongly associated with neurohormonal measures than LVEF. Cardiac adverse events [CAE; HF progression (HFP), life-threatening arrhythmia (ARR), and cardiac death (CD)] and all-cause mortality (ACM) were recorded prospectively in 954 patients with HF and LVEF ≤ 35%: 852 in sinus rhythm (SR) and 102 in AF. Cox proportional hazard models found that the univariate hazard ratios (HR) for LVEF and the first CAE (primary outcome), HFP, ARR, CD, and ACM were significant in SR (0.933, P

We previously developed an operator-interactive method for the measurement of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and end-systolic volume (ESV) and end-diastolic volume (EDV) using single-photon emission tomographic equilibrium radionuclide angiocardiography (SPECT ERNA). We aimed to compare our SPECT ERNA method with cardiac MRI (CMRI) for the determination of ventricular measures.Paired measurements of LV and RV EFs and ESV and EDV were carried out by SPECT ERNA and CMRI in a group of patients who had myocardial infarction due to left anterior descending coronary artery thrombosis.SPECT ERNA and CMRI provided similar estimations of the mean (SD) LV ESV [61 (23) vs. 61 (32) ml; P=0.99] and LV EDV [134 (29) vs. 141 (44) ml; P=0.28]. The mean (SD) LV EF by SPECT ERNA was slightly but significantly smaller than that by CMRI [0.55 (0.10) vs. 0.58 (0.11) ml; P=0.03]. SPECT ERNA, compared with CMRI, produced similar mean (SD) values of RV ESV [62 (17) vs. 67 (17) ml; P=0.10] and RV EDV [153 (28) vs. 149 (29) ml; P=0.51] and somewhat larger mean (SD) RV EF [0.60 (0.06) vs. 0.55 (0.06) ml; P0.001]. Excellent correlations were found between SPECT ERNA and CMRI for combined LV ESV and EDV (R=0.85, P0.001) and combined RV ESV and EDV (R=0.85, P0.001).This study further validates SPECT ERNA as a method to measure LV and RV EF, ESV, and EDV.

A 40-year-old man with a history of prior closed head injury, insulin-dependent diabetes mellitus type 2, and nicotine dependence was evaluated at Saint Marys Hospital, a Mayo Clinic–affiliated hospital in Rochester, MN, after being found unconscious at his home.

Successful thromboendarterectomy for chronic thromboembolic pulmonary hypertension promptly improves right ventricular (RV) function by decreasing RV volume and increasing ejection fraction (EF). Single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) has been validated as a measure of RV and left ventricular (LV) volume and EF.Nine patients with chronic thromboembolic pulmonary hypertension underwent electron beam computed tomography (EBCT) and SPECT ERNA cardiac studies before and after thromboendarterectomy. EBCT and SPECT ERNA measures of RV and LV volume and EF were compared. Before thromboendarterectomy, EBCT and SPECT ERNA RV and LV volumes and RV EF were similar. LV EF was within the normal range with both methods but was slightly greater (P = .004) when measured by EBCT (mean +/- SD, 0.61 +/- 0.08) compared with SPECT ERNA (0.54 +/- 0.10). Thromboendarterectomy measured by EBCT and SPECT ERNA produced marked similar and significant decreases in RV end-systolic (-72 +/- 59 mL vs -58 +/- 25 mL) and end-diastolic (-75 +/- 85 mL vs -76 +/- 32 mL) volumes and similar slight increases in RV EF (0.12 +/- 0.07 vs 0.05 +/- 0.06). Slight decreases in mean LV end-systolic (-19 +/- 23 mL vs -5 +/- 13 mL, P = .05) and end-diastolic (-32 +/- 53 mL vs -9 +/- 31 mL, P = .21) volumes occurred, with little change in mean LV EF (0.05 +/- 0.07 vs 0.00 +/- 0.10).SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy.

The frequency and determinants of early rapid diastolic filling abnormalities in the community and in cardiac patients are poorly understood.Early left ventricular (LV) rapid filling was assessed via equilibrium radionuclide angiocardiography in 70 community volunteers (LV ejection fraction [EF]or = 0.50) and 778 cardiac patients, all aged at least 45 years. The frequency of early rapid filling and the independent clinical, therapeutic, and hemodynamic variables predictive of early rapid filling abnormality were determined. Depending on the parameter assessed, early rapid filling was abnormal in 27% to 54% of the community volunteers, 34% to 53% of cardiac patients with an LVEF of 0.50 or greater, and 42% to 67% of cardiac patients with an LVEF lower than 0.50. On the basis of multivariate analysis, models of clinical, therapeutic, and hemodynamic variables were modestly predictive of early rapid filling abnormality. Age, sex, valvular insufficiency, hypertension, digoxin use, and heart rate were independent determinants of early rapid filling.In participants aged older than 44 years, early rapid filling was frequently abnormal in the community volunteers and in patients with an LVEF of 0.50 or greater and was most common in patients with an LVEF lower than 0.50. Clinical, therapeutic, and hemodynamic variables had modest independent predictive value for early rapid filling abnormality.

Background Heart failure with preserved left ventricular ejection fraction (LVEF) suggests isolated diastolic dysfunction. Aim The purpose of this study was to determine if systolic and diastolic dysfunction occurred with preserved LVEF. Methods Equilibrium resting radionuclide ventriculograms from 439 patients with an LVEF ≥0.50 were used to determine LV peak filling rate (PFR) and peak ejection rate (PER) in end-diastolic volumes per second and LV end-systolic volume (ml). Patients with low-normal (n=147; range, 0.50−0.58; mean±S.D., 0.53±0.02), intermediate-normal (161, 0.59−0.64, 0.61±0.02), and high-normal (131, 0.65−0.94, 0.72±0.06) LVEF were compared. Results From low-normal to intermediate-normal to high-normal LVEF, LV end-systolic volume decreased (93±36, 71±33, 43±26, respectively, P

To further characterize the effects of heart rate on systolic and diastolic function in patients with idiopathic dilated cardiomyopathy (IDCM), it was hypothesized that the relationship between heart rate and left ventricular systolic and diastolic function would be unaltered by beta-blockade and exercise.Eighteen patients with IDCM were randomized in a double-blind manner to receive either metoprolol or placebo for 3 months. Before and after 3 months of therapy, resting and exercise radionuclide left ventriculograms were obtained for assessment of left ventricular systolic and diastolic function.At rest, metoprolol treatment compared with placebo was associated with decreased heart rate (61 +/- 11 vs 99 +/- 10 beats/min, P.0001) and an increased left ventricular ejection fraction (0.32% +/- 0.10% vs 0.17% +/- 0.08%, P =.01). With exercise, metoprolol compared with placebo caused a decreased heart rate (86 +/- 18 vs 126 +/- 43 beats/min, P =.056), an increase in left ventricular ejection fraction (0.32% +/- 0.14% vs 0.19% +/- 0.07%, P =.052), a longer time to peak filling rate (164 +/- 21 vs 127 +/- 17 ms, P =.005), and a decreased peak filling rate (5.41 +/- 1.71 vs 8.40 +/- 1.85 stroke volumes/s, P =.012). Before beta-blockade, heart rate at rest was negatively correlated to left ventricular ejection fraction and positively correlated to peak filling rate; with exercise, the relationships of heart rate to left ventricular ejection fraction and peak filling rate were similar. After metoprolol treatment, the heart rate continued to have a similar positive correlation with the peak filling rate at rest and with exercise.In patients with IDCM, systolic and diastolic cardiac function, at rest and with exercise, was related to heart rate. After beta-blockade, at rest and with exercise, diastolic function continued to be related to heart rate.

Left ventricular function is modified by respiration and pericardial constraint. The aim of this study was to compare left ventricular systolic and diastolic function during inspiration and expiration in four patient groups: patients (1) without cardiac disease, (2) with severe pulmonary disease, (3) with cardiac amyloid and (4) with pericardial constriction (before and after pericardiectomy). Using blood-pool left ventriculography with modified gating, we obtained time-activity curves at the onset of inspiration and expiration. On inspiration and expiration, patients with pericardial constriction and patients with cardiac amyloid were significantly different from those without cardiac disease and those with severe pulmonary disease, in that left ventricular ejection fraction (LVEF) was less, peak filling rate was greater, time to peak filling rate was shorter, and rapid filling fraction was increased. When inspiration and expiration were compared, time to left ventricular peak filling rate was shorter (P = 0.05) on inspiration (118 +/- 48 ms) than on expiration (168 +/- 35 ms) in patients with pericardial constriction. No other measures differed between inspiration and expiration in pericardial constriction, and left ventricular function was unaffected by respiration in the other groups. Time to left ventricular peak filling rate was 49 +/- 69 ms less on inspiration than on expiration in pericardial constriction and this difference was significantly different (P = 0.04) from that in patients with cardiac amyloid (34 +/- 58 ms greater), patients without cardiac disease (2 +/- 69 ms greater) and patients with severe pulmonary disease (19 +/- 63 ms less). In pericardial constriction, pericardial resection caused an increase in LVEF without a change in left ventricular diastolic filling but abolished the differences present between inspiration and expiration in time to left ventricular peak filling rate. This respiratory response in time to left ventricular peak filling rate may be valuable in the diagnosis of pericardial constriction.

The prognostic value of exercise thallium-201 imaging has been well established in referral patient populations at tertiary care centers, but these results may be influenced by referral bias.This study was performed to evaluate the prognostic value of thallium imaging in a community-based population of 446 residents of Olmsted County, Minn. Eleven variables were prospectively selected and tested for their associations with outcome end points.Four variables (age, history of myocardial infarction, number of abnormal thallium segments on the postexercise images, and increased thallium lung uptake) contained the most independent prognostic information. For the end point overall mortality rate, the multivariate chi-square values were 17.2 (p0.0001) for age and 20.9 (p0.0001) for the number of abnormal thallium segments on the postexercise images. Five-year survival rate for patients older than the median age of 59 years with an abnormal scan was 84% versus 97% for patientsor = 59 years of age with a normal scan.Exercise thallium imaging was useful for prognostic purposes in this relatively low-risk community population, confirming the findings of referral population studies.

This study sought to determine the prevalence of spontaneous reperfusion of an infarct-related artery (IRA) and associated myocardial salvage in the absence of thrombolysis or angioplasty. Twenty-one patients with acute myocardial infarction received only heparin and aspirin. At a median of 18 hours after presentation, 12 patients (57%) had angiographic patency of the IRA. Technetium-99m sestamibi was injected acutely on presentation and again at hospital discharge. Acute and final perfusion defect sizes were measured. Their difference, myocardial salvage, was calculated along with salvage index (myocardial salvage/acute defect). Comparing patients with a patent versus occluded IRA, myocardium at risk was similar (16% +/- 12% vs 12% +/- 9% left ventricle, p = NS); however, myocardial salvage (9% +/- 9% vs -2% +/- 7% left ventricle, p = 0.01), and salvage index (0.62 +/- 0.37 vs 0.19 +/- 0.33, p = 0.01) were greater in patients with spontaneous reperfusion. Resolution of chest pain was greater in patients with a patent IRA (100% vs 55%, p = 0.003). Spontaneous reperfusion of the IRA occurs frequently in patients with acute myocardial infarction and is associated with significant myocardial salvage.

Objectives. This study sought to determine the accuracy of the initial 12-lead electrocardiogram (ECG) in predicting final infarct size after direct coronary angioplasty for myocardial infarction and to examine which physiologic variables known to be determinants of outcome the ST segment changes most closely reflect. Background. Myocardium at risk, collateral flow and time to reperfusion have been shown to be independent physiologic predictors of infarct size in animal and clinical models. However, such measurements may be difficult to perform on a routine basis in patients with myocardial infarction. The standard 12-lead ECG is inexpensive and readily available. Methods. Sixty-seven patients with acute myocardial infarction, ST segment elevation and duration of chest pain

Early tomographic myocardial perfusion imaging with technetium-99m sestamibi was performed during inferior wall acute myocardial infarction to determine the relation between the amount and location of myocardium at risk and the presence or absence or anterior ST depression. The total size of the acute perfusion defect and its lateral and septal borders were measured in 29 consecutive patients who were admitted with > 30 minutes of chest pain and acute inferior ST elevation on their initial electrocardiogram. The 22 patients with anterior ST depression had significantly more left ventricular myocardium at risk than the 19 patients who did not have anterior ST depression (23 +/- 2% of the left ventricle vs 15 +/- 1%, p = 0.008). All 8 patients with > 25% of the left ventricle at risk had anterior ST depression. Patients with anterior ST depression had a significantly greater lateral extent of the acute perfusion defect (49 degrees +/- 8 degrees from the midinferior wall vs 23 degrees +/- 7 degrees, p = 0.002). There was no difference in the septal border of the perfusion defect between patients with and without anterior ST depression (-44 degrees +/- 4 degrees vs -46 degrees +/- 7 degrees, p = NS). No patient had a measurable anterior perfusion defect. Although there is considerable overlap between groups with and without anterior ST depression, anterior ST depression is a simple and readily available indicator of myocardium at risk in inferior wall acute myocardial infarction.

Background— Patients with diabetes mellitus have accelerated progression of heart failure and often have impaired cardiac sympathetic innervation. The present study examines the implications for heart failure progression of cardiac sympathetic denervation, assessed by I-123 metaiodobenzylguanidine imaging, in diabetic compared with nondiabetic subjects. Methods and Results— We evaluated 343 diabetic and 618 nondiabetic subjects with New York Heart Association class II or III heart failure and a left ventricular ejection fraction ≤35% over a median follow-up of 17 months. A multivariable Cox proportional hazards model was used to examine the influence of clinical variables, b-type natriuretic peptide, plasma norepinephrine, left ventricular ejection fraction, and I-123 metaiodobenzylguanidine imaging parameters on time to a heart failure event. The late heart-to-mediastinum (H/M) ratio and the interaction term of diabetes mellitus with the prospectively selected late H/M ratio Conclusions— The combination of diabetes mellitus and I-123 metaiodobenzylguanidine H/M ratio is an independent predictor of heart failure progression, confirming the high risk of diabetic subjects with impaired cardiac sympathetic nerve function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00126438 and NCT00126425.

Diastolic filling can be measured by radionuclide ventriculography with use of several techniques including those based on gated and list-mode acquisitions, the first-pass method, and the nuclear probe. Radionuclide ventriculography specifically assesses volumes, rates of volume change, and intervals during ventricular filling. Normal values for diastolic filling measurement vary depending on the individual radionuclide methods used and the age of the patient. Comparative studies of the radionuclide method with contrast angiographic and Doppler echocardiographic techniques for measuring diastole are discussed, and the advantages and disadvantages of the radionuclide techniques are explored. The role of radionuclide assessment of diastolic function in specific clinical examples of hypertrophic cardiomyopathy, hypertension, anthracycline-induced cardiomyopathy, and coronary artery disease is reviewed. Radionuclide ventriculography is an accurate and easily applicable procedure for studying left ventricular volume changes in diastole.

Episodic behavior associated with impairment of consciousness is a protean clinical manifestation that may suggest a wide range of medical or neurologic disorders. We describe a patient whose symptoms of an epigastric "aura" followed by loss of consciousness suggested temporal lobe epilepsy. The episodic behavior was refractory to antiepileptic drug therapy. Prolonged video-electro-encephalographic monitoring confirmed that the clinical events were cardiogenic related to asystole. Antiepileptic drug therapy was discontinued, and a cardiac pacemaker was inserted. The clinical patterns that distinguish syncope from seizures and the importance of prolonged video-electroencephalographic monitoring are discussed.

The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the PURSUIT trial population for 30-day mortality prediction.The PURSUIT risk score was calculated for 337 consecutive Olmsted County residents with non-ST-elevation acute myocardial infarction admitted to the coronary care unit of our institution from 1988 through 1998. Predischarge ejection fraction (EF) measurement was available for 246 patients (73%). After excluding patients with prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%. Among 30-day survivors, mortality at 1 year was 7.9%.Mean age was 70 +/- 13 years, and 37% of patients were women. Mean predischarge EF was 52% +/- 16%. Patients with higher PURSUIT risk score had lower EF (P.001). Three-vessel (or =70% stenosis in all 3 coronary arteries) or left main (or =50% stenosis) coronary artery disease was present in 60 of 219 patients (27%) who had coronary angiography. Higher PURSUIT risk score was associated with greater likelihood of 3-vessel or left main disease (P.001). The PURSUIT risk score had very good predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day to 1-year, C-statistic = 0.77) mortality.The PURSUIT risk score correlates with EF, angiographic severity of coronary artery disease, and short- and long-term mortality of nonselected patients with non-ST-elevation acute myocardial infarction.

Diastolic and systolic left ventricular (LV) function may be affected early after the initiation of doxorubicin therapy. However, the role of mediastinal radiation and other cytotoxic agents in the production of these early cardiac effects is unclear. In this study LV diastolic and systolic function were assessed before and after doxorubicin (223+/-122 mg.m-2; range, 40-618) in 33 patients. After doxorubicin, LV ejection fraction declined (0.61+/-0.08 to 0.56+/-0.08, P=0.0008), peak filling rate decreased (3.38+/-1.10 to 2.82+/-0.62 end diastolic volumes/s, P=0.006), and time to peak filling rate increased (162+/-39 to 182+/-45 ms, P=0.04). The changes in LV systolic and diastolic function were not related to doxorubicin dose and the use of other cytotoxic agents; the decrease in LV ejection fraction with doxorubicin was more notable in men and in patients who received mediastinal irradiation concurrently with doxorubicin. It is concluded that the use of doxorubicin was associated with the simultaneous early development of LV systolic and diastolic dysfunction. Male gender and concurrent mediastinal irradiation were independent influences, but doxorubicin dose and the use of other cytotoxic agents were not associated with worse cardiac dysfunction.

To determine whether an increased QRS duration in the absence of bundle branch block (BBB) on the presenting electrocardiogram of patients with acute myocardial infarction (AMI) is associated with decreased survival, we retrospectively reviewed 781 consecutive patients admitted to the coronary care unit of our institution with AMI without BBB between 1988 and 1998. In patients with ST elevation AMI (n = 412), the groups with QRS durationor =100 ms and100 ms had similar survival. Conversely, in patients with non-ST elevation AMI (n = 369), in-hospital, 1-, 3-, and 5-year survival was 84.4%, 75.6%, 66.7%, and 52.2%, respectively, in the group with QRSor =100 ms compared with 95.4%, 89.2%, 83.8%, and 74.3%, respectively, in the group with QRS100 ms (p0.01, log-rank test). In patients with non-ST elevation AMI, those with QRS durationor =100 ms were more likely to be men, to have had a prior AMI that healed, to be in Killip class II, III, or IV, and to have lower ejection fraction than patients with QRS duration100 ms. After adjusting for age, sex, prior AMI or stroke, heart rate, and Killip class on admission, QRS durationor =100 ms was independently associated with in-hospital and overall mortality in patients with non-ST elevation AMI. QRS durationor =100 ms in the absence of BBB is an independent predictor of increased mortality in patients with non-ST elevation AMI.

We hypothesized that, within the normal range of resting heart rate, heart rate and left ventricular ejection fraction would be inversely correlated and heart rate and left ventricular filling would be correlated in patients with dilated cardiomyopathy and not correlated in patients with normal cardiac function. At rest, heart rate, left ventricular ejection fraction, and three measures of diastolic filling (time to peak filling rate, peak filling rate, and first half filling fraction) were recorded using radionuclide ventriculography in subjects with no cardiac disease, patients with idiopathic dilated cardiomyopathy, and patients with dilated cardiomyopathy associated with ischemic heart disease. Heart rate had significant inverse correlations with left ventricular ejection fraction (r=-0.55, P=0.0007) and time to peak filling rate (r=-0.47, P=0.005) and a positive correlation with peak filling rate (r=0.73, P

Purpose: To determine electrocardiographic features associated with myocardial salvage following reperfusion therapy in patients with inferior myocardial infarction. Patients and Methods: Ninety-two consecutive patients with acute inferior myocardial infarction were treated with reperfusion therapy in a tertiary care center. Several features were measured on the presenting electrocardiogram, including the presence or absence of ST depression in the chest leads and the total magnitudes of ST elevation or depression, and were then evaluated for their association with myocardial salvage. Myocardial salvage (% of left ventricle) was the difference between myocardium at risk and final infarct size. Tomographic myocardial perfusion imaging with technetium-99m sestamibi was performed acutely to measure myocardium at risk and repeated prior to hospital discharge to measure final infarct size. Results: The amount of myocardium at risk of infarction in the 92 patients was 19.1% ± 11.3% (range 1% to 68%), and the final infarct size was 10.6% ± 10.0% (range 0% to 45%). Thus, myocardial salvage in the 92 patients was 8.5% ± 8.4% (range −11% to 35%) of the left ventricle, or 0.51 ± 0.38 (range 0.0 to 1.0) when expressed as a fraction of the myocardium at risk (salvage index). The presence or absence of anterior ST depression was the only one of seven electrocardiographic variables that was associated with myocardial salvage. Myocardial salvage was significantly greater in patients with anterior ST depression compared with those without it (10.6% ± 9.0% versus 5.9% ± 6.7%, P = 0.025). Myocardium at risk was significantly greater in patients with anterior ST depression compared with those without the depression (22.8% ± 12.2% versus 14.6% ± 8.3%, P = 0.0006), and infarct size tended to be larger (12.1% ± 10.4% versus 8.7% ± 9.4%, P = 0.10). Myocardial salvage as a fraction of the myocardium at risk (salvage index) was similar between the two patient groups (0.52 ± 0.37 versus 0.50 ± 0.39, P = NS). Conclusion: The presence of anterior ST depression during inferior myocardial infarction identifies a group of patients with the potential for greater myocardial salvage with reperfusion therapy. Such patients derive greater absolute benefit from reperfusion therapy because they have a larger amount of myocardium at risk, although their response to therapy (salvage index) is not intrinsically different.

Left ventricular (LV) filling was studied in 18 healthy subjects and 19 mildly hypertensive patients before and after 50% and 70% of maximal supine exercise using radionuclide ventriculography. In addition, in the hypertensive patients, the effects of oral verapamil and lisinopril treatment on LV filling before and after exercise were studied. At rest, hypertensive patients compared with healthy subjects had a lower peak filling rate, ratio of peak filling to peak emptying rate, first-half filling fraction, and a longer isovolumic duration. With exercise, LV filling measures were not different between healthy subjects and hypertensive patients. In the hypertensive patients at rest, compared with before treatment, lisinopril prolonged isovolumic duration and verapamil had no effect on LV filling; at 50% maximal exercise compared with before treatment, verapamil shortened the time to peak filling rate and isovolumic duration and increased first-half filling fraction but, at 70% maximal exercise, verapamil had no effect, whereas lisinopril did not alter exercise LV filling at either exercise level. Thus, the early abnormal LV filling in mildly hypertensive patients is influenced by therapeutic interventions both at rest and with exercise.

BACKGROUND In acute myocardial infarction, residual flow to the infarct zone either through antegrade flow in the infarct-related coronary artery or collateral flow from the non-infarct-related arteries is often present before reperfusion therapy. The purpose of this study was to assess the influence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before successful direct angioplasty on infarct size and myocardial salvage in patients with acute evolving myocardial infarction. METHODS AND RESULTS Sixty patients with acute evolving myocardial infarction underwent direct successful angioplasty without prior thrombolytic therapy. The myocardium at risk of infarction, the final infarct size, and myocardial salvage were measured by tomographic perfusion imaging with 99mTc sestamibi. Antegrade flow in the infarct-related artery before intervention was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study group classification. Collateral flow to the infarct zone before angioplasty was also graded (0 through 3, 0 being no collateral flow). The presence of even minimal antegrade flow before angioplasty (TIMI grade 1) in the infarct-related artery compared with absent flow was associated with a significant reduction in final infarct size (9 +/- 17% versus 23 +/- 19% of left ventricle, P = .02) and a significant increase in myocardial salvage (23 +/- 16% versus 14 +/- 13% of left ventricle, P = .05) after angioplasty. When antegrade flow in the infarct-related artery was absent before angioplasty, the presence of collateral flow before angioplasty resulted in a significantly smaller final infarct size (P = .01) and more myocardial salvage (P = .05) after angioplasty. Both antegrade infarct-related artery flow and collateral flow to the infarct zone had significant independent ability to predict infarct size after angioplasty. When collateral grade and TIMI grade were added to provide an estimate of residual flow, a model including residual flow, myocardium at risk, and the interaction of residual flow and infarct site explained 83% of the variability in infarct size after angioplasty. CONCLUSIONS The presence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before direct angioplasty in acute evolving infarction results in a smaller infarct size after direct successful angioplasty.

The purpose of this study was to examine the relationship between the presence or absence of ST segment depression in inferior leads (II, III, and aVF) and ST segment elevation in lateral (I and aVL) or left precordial (V5 and V6) leads with the amount and location of myocardium at risk for infarction in patients with acute anterior myocardial infarction. Forty-three patients with anterior infarctions were injected with technetium 99m-sestamibi when they were first seen and underwent tomographic imaging to measure the amount and location of myocardium at risk. Patients with inferior ST depression (n = 10) compared with those without ST depression (n = 33) had perfusion defects that extended significantly further into the lateral wall (47 degrees vs 20 degrees, p = 0.04) and larger anterior injury vectors (6.47 vs 4.92, p = 0.008). There was no significant association with the percentage of myocardium at risk, disease of the right coronary artery, the presence of an inferior perfusion defect, or the size of the inferior injury vector. Among the patients with ST elevation in lateral leads (n = 16) compared with those without (n = 27), there was a significantly more lateral defect border (47 degrees vs 25 degrees, p = 0.007) and a larger anterior injury vector (6.07 vs 4.81, p = 0.01). There was no significant correlation with the percentage of myocardium at risk. A significant relationship could not be demonstrated between the presence of ST elevation in the left precordial leads and any measure of the amount or location of myocardium at risk. These data support the theory that inferior ST depression in patients with transmural anterior ischemia is a "reciprocal" finding and does not represent inferior ischemia. The presence of inferior ST depression or lateral ST elevation is associated with a more lateral perfusion defect. Neither of these ECG findings is associated with the amount of myocardium at risk for infarction.

A 9-year-old boy with clinical stage IIA Hodgkin's disease underwent radiotherapy to the neck and mediastinum. Twenty-two years later, he sought medical attention because of angina pectoris. Cardiac catheterization revealed proximally located high-grade stenoses of the left main, left anterior descending, circumflex, and right coronary arteries. He underwent coronary artery bypass grafting with use of the left internal mammary artery to the left anterior descending coronary artery and reversed saphenous vein grafts to the circumflex and right coronary arteries. The postoperative course was uncomplicated. Previous radiotherapy to the mediastinum should be considered a risk factor for the development of premature coronary artery disease. Surgical revascularization is the preferred method of management. A combination of an internal mammary artery graft and a saphenous vein graft should be used in young patients.

The 12-lead electrocardiogram in 23 patients with an evolving first myocardial infarction (12 anterior and 11 inferior) was correlated with the myocardial area at risk measured by tomographic perfusion imaging with technetium-99m sestamibi. Of several electrocardiographic factors, only the extent and quantity (with and without R-wave normalization) of ST depression differed significantly between inferior and anterior evolving infarction. The myocardial area at risk was greater in anterior than in inferior evolving infarction. The extent of the myocardium at risk correlated modestly (r = 0.58) with total ST displacement in anterior evolving infarction and with total ST depression normalized to the R wave (r = 0.70) in inferior evolving infarction. Because of the large standard errors (9 to 15% of the left ventricle), estimates of the myocardial area at risk based on these electrocardiographic variables have minimal clinical value in the individual patient.

The relation between left ventricular (LV) filling variables measured by gated blood pool radionuclide ventriculography and clinical symptoms and survival was examined in 93 patients who had decreased LV systolic function. The diastolic data were not significantly associated with clinical symptoms. Time to peak filling rate, peak filling rate and ejection fraction were associated independently with survival free of cardiac death (chi-square = 7.74, S.91 and 3.92, respectively, by stepwise Cox regression analysis). A short time to peak filling rate or increased peak filling rate was associated with decreased survival, whereas the opposite indicated a good prognosis. One-year Kaplan-Meier survival was 73 and 98% when time to peak filling rate was below or above the median value of 167 ms, respectively, 82 and 90% when peak filling rate was above or below the median value of 1.67 end-diastolic volumes per second, respectively, and 76 and 95% when LV ejection fraction was below or above the median value of 0.35, respectively. Thus, filling variables (time to peak filling rate and peak filling rate) measured by radionuclide ventriculography may be valuable in predicting survival in patients with decreased LV systolic function.

BACKGROUND Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

To assess the ability of the 12-lead electrocardiogram to estimate infarction size after reperfusion therapy for acute myocardial infarction.The presence or absence of Q waves and the Selvester QRS score obtained before and after hospital discharge were compared with radionuclide estimates of infarction size and ejection fraction at discharge and 6 weeks later, regional wall motion at discharge and 6 weeks later, and myocardial perfusion defect size quantitated with Tc-99m-sestamibi at discharge.A tertiary referral center.A consecutive series of 43 patients with acute myocardial infarction who received acute reperfusion therapy and were assessed using 12-lead electrocardiography, radionuclide angiography, and Tc-99m-sestamibi tomographic imaging before discharge.All 43 patients received acute reperfusion therapy: 21 patients received intravenous tissue plasminogen activator, and 22 patients underwent primary percutaneous transluminal coronary angioplasty.The correlation of QRS score and Q waves with three radionuclide estimates of infarction size.A significant correlation was found between myocardial perfusion defect size at discharge and both left ventricular ejection fraction and regional wall motion at discharge and 6 weeks later (r = -0.71 to -0.81; all comparisons, P less than 0.001). Little correlation was found between electrocardiographic findings and radionuclide measurements of left ventricular function and perfusion. Presence or absence of Q waves at discharge was not associated with any difference in ejection fraction, regional wall motion, or perfusion defect at discharge. No correlation was found between QRS score and ejection fraction or myocardial perfusion defect size at discharge. The QRS score at discharge correlated only weakly with regional wall motion at discharge and 6 weeks later. This lack of correlation was unchanged when electrocardiograms obtained after hospital discharge were analyzed.Although inexpensive and readily available, the 12-lead electrocardiogram does not appear to provide a reliable estimate of infarction size after reperfusion therapy for acute myocardial infarction.

From a consecutive series of patients who underwent rest and exercise radionuclide angiography over several years, we retrospectively identified 34 patients with left main coronary artery disease and 103 patients with three-vessel coronary artery disease who did not have significant left main disease. The results of gated equilibrium radionuclide angiography were compared in these 2 groups. Multiple exercise hemodynamic, exercise electrocardiographic, and exercise radionuclide angiographic parameters were considered in an attempt to separate the 2 groups. The only parameter that was significantly different between the 2 groups was exercise heart rate. However, no value of the exercise heart rate could meaningfully separate the 2 groups. Despite their known difference in prognosis, patients with left main and three-vessel disease had very similar exercise performance and could not be distinguished from one another by exercise electrocardiography or exercise radionuclide angiography. The inability to distinguish these two groups is a clear limitation of noninvasive exercise modalities.

To examine the sequential changes in left ventricular volume after thrombolytic therapy for acute myocardial infarction, gated radionuclide ventriculography was performed within 12 hours of thrombolysis and at 1 and 6 weeks in 34 consecutive patients who received intravenous thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial. Angiographic confirmation of immediate reperfusion (mean 5.6 hours after onset of symptoms) that persisted at 24 hours was noted in 24 patients; 10 patients were not reperfused. A small (9.5%), but significant (p = 0.05), increase in end-diastolic volume index was noted in the reperfused group between 1 and 6 weeks; however, a marked degree of dilatation (35%) was noted in the nonreperfused group (p = 0.01). The change in left ventricular volume between 1 and 6 weeks differed in the 2 groups for both end-diastolic volume index and end-systolic volume index (p = 0.01 and p = 0.02, respectively). By 6 weeks, both end-diastolic volume index and end-systolic volume index were greater in the nonreperfused group (p < 0.05). Between the acute and 6-week studies, definite increases in end-diastolic volume index (p < 0.05) and end-systolic volume index (p < 0.01) occurred commonly in the nonreperfused group but rarely in the reperfused group. Compared to the nonreperfused group, the reperfused group also had significantly higher ejection fractions at both 1 and 6 weeks (p < 0.05). The change in end-diastolic volume index between 1 and 6 weeks correlated significantly and inversely with the ejection fraction at 1 week (r = -0.60, p < 0.001). These results indicate that ventricular dilatation occurs between 1 and 6 weeks after myocardial infarction, is proportional to systolic dysfunction and may be largely prevented by successful thrombolytic reperfusion.

Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise.

Radionuclide angiography was used to study the effects of supine and upright bicycle exercise and handgrip exercise in 17 (12 well-trained) normal subjects before (control) and immediately after the administration of propranolol (160 mg/day for 4 days). Cardiac hemodynamic values were related to position in that control left ventricular volumes and the cardiac index were greater in the supine position than in the upright at rest but resting left ventricular ejection fraction was similar in both positions. The pressure volume index was greater in the upright position than in the supine. At maximal exercise before treatment, however, similar cardiovascular hemodynamic measurements were recorded in both positions. Propranolol increased left ventricular end-diastolic volume at rest and at maximal exercise. Left ventricular end-systolic volume, however, was substantially greater only in the upright position both at rest and at maximal exercise when compared with control values. Heart rate, systolic arterial pressure, cardiac index, and pressure volume index were decreased at rest and maximal exercise after treatment with propranolol. Ejection fraction was decreased in the upright position after propranolol administration but was unchanged in the supine position. Handgrip exercise primarily increased heart rate and arterial pressure and did not affect cardiac volume, and this response was unaffected by propranolol.

This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography.Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus −2 ml/m2, p = 0.002).The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.

Left ventricular (LV) filling at rest was studied by radionuclide ventriculography using alternate R-wave gating in 42 patients (29 men, 13 women) who had a low likelihood of cardiac disease. LV filling measurements differed little between men and women. Age was correlated positively with atrial filling duration (r = 0.55), atrial filling duration fraction (r = 0.52) and atrial filling fraction (r = 0.56) and negatively with rapid filling fraction (r = -0.58). Age was not correlated with peak filling rate, time to peak filling rate and first-half filling fraction. The heart rate at rest was significantly negatively correlated with rapid (r = -0.62), slow (r = -0.81) and atrial (r = -0.72) filling durations, but not with isovolumic duration. The heart rate at rest was weakly positively correlated with peak filling rate in end-diastolic volume per second (r = 0.36) and negatively correlated with first-half filling fraction (r = -0.35). Systolic pressure at rest influenced atrial filling duration. LV ejection fraction and end-diastolic volume index were not correlated significantly with LV filling in relatively normal subjects.

The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.

The exercise response of the ratio of systolic blood pressure to end-systolic volume was studied in 243 patients with chest pain and coronary artery disease who underwent supine rest and exercise equilibrium radionuclide angiography. There was a wide variation in both rest and exercise variables in this group. The exercise response of the systolic pressure/volume ratio also varied greatly, ranging from a decrease of 59% to an increase of 136%. Twenty-one clinical, catheterization and radionuclide angiographic variables were examined to determine their relation to the exercise response of the systolic pressure/volume ratio; nine variables were individually correlated with this ratio. Multiple regression analysis identified the change in end-diastolic volume index with exercise, rest systolic blood pressure, coronary artery Gensini score and peak work load as significant independent predictors of the exercise response of the systolic pressure/volume ratio; the latter correlated significantly with the change in ejection fraction with exercise (r = 0.73, p less than 0.0001). Its sensitivity for the detection of coronary artery disease in the study group (84%) and its "normalcy rate" in a group of 120 patients with a low likelihood of coronary artery disease (81%) were similar to those of the peak exercise ejection fraction (75 and 82%, respectively). These results demonstrate that the exercise response of the systolic pressure/end-systolic volume ratio is a complex response that is influenced by several pathophysiologic variables in the presence of coronary artery disease. It does not offer any advantage over ejection fraction measurements for the detection of exercise-induced ischemia.

The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables—the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient—can provide practical estimates of the risk of having ten main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful uoninvasive estimate of the risk of having significant left main or three vessel disease.

Left ventricular diastolic filling measurements were determined by means of standard consecutive R-wave gating, list mode acquisition, and alternate R-wave gating. Time-activity curves obtained by the latter two methods were equally accurate in quantifying rapid, slow, and atrial left ventricular filling, whereas curves obtained by means of standard gating were inadequate for this purpose.

We investigated whether exercise radionuclide angiography provides prognostic information in addition to that identified by resting left ventricular function and coronary anatomy in patients with medically treated coronary artery disease. Clinical follow-up (median, 21.7 months) was obtained in 424 medically treated patients who underwent exercise radionuclide angiography and coronary angiography. The mean age of the study population was 58 years, and 67% were men. Cardiac death occurred in 16 patients, nonfatal myocardial infarction in 16, and nonfatal out-of-hospital cardiac arrest in 1. Univariate analysis showed that multiple variables were associated with future cardiac events, including number of diseased vessels, exercise and rest radionuclide ejection fraction, history of myocardial infarction, exercise and rest left ventricular end-systolic and end-diastolic volume indices, peak exercise workload, age, abnormal resting electrocardiogram, and peak exercise ST-segment depression. Only three variables were independently associated with cardiac events on follow-up: number of diseased vessels, radionuclide ejection fraction at rest, and age. In patients with three-vessel disease and a resting radionuclide ejection fraction of more than 40%, a subgroup with higher risk could not be identified on the basis of exercise radionuclide response.

The ability of radionuclide variables obtained at rest and at peak exercise to discriminate the number of stenosed (greater than or equal to 70% luminal diameter narrowing) major coronary arteries was evaluated in 296 patients undergoing supine exercise radionuclide ventriculography. Stepwise linear discriminant analysis of the data from the first 200 patients identified a significant (p less than 0.001) discriminatory combination. Application of this function to the remaining 96 patients provided correct classification of arteriographically determined zero, one, two, and three stenosed arteries in 59%, 18%, 14%, and 60% of cases, respectively. The discriminant function classified minimal stenoses (zero or one artery) and multivessel stenoses (two or three arteries) correctly by arteriography in two thirds of cases in each group. Arteriographic presence of three stenoses was unlikely in those classified as having no stenosis, and absence of stenosis was rare in those classified as having three stenoses. Exercise radionuclide ventriculography is most helpful in identifying minimal and multivessel coronary disease rather than number of stenosed major coronary arteries.

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.

A false aneurysm compressing an ascending aortic composite valved graft, leading to disc interference and aortic insufficiency with congestive heart failure, was successfully repaired. An alternative method of constructing the distal anastomosis that would obviate this problem is described.

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.