Prognostic significance of (123)I-mIBG SPECT myocardial imaging in heart failure: differences between patients with ischaemic and non-ischaemic heart failure.

AIMS: The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial (123)I-mIBG and (99m)Tc-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 (123)I-mIBG myocardial SPECT, alone and in combination with (99m)Tc 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 (123)I-mIBG/(99m)Tc 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 (<20% of myocardium), but with a large discrepancy between (123)I-mIBG and (99m)Tc tetrofosmin defect sizes, were at highest risk of cardiac death. CONCLUSIONS: Prognostic significance of patterns of (123)I-mIBG and MPI uptake differ between IHF and NIHF subjects. SPECT imaging may provide new insights into underlying disease processes in HF, including the degree of dysinnervation in areas with preserved myocardial perfusion in non-ischaemic HF patients.

Quantitative iodine-123-metaiodobenzylguanidine (MIBG) SPECT imaging in heart failure with left ventricular systolic dysfunction: Development and validation of automated procedures in conjunction with technetium-99m tetrofosmin myocardial perfusion SPECT.

BACKGROUND: The purpose of this study was to develop and validate new approaches to quantitative MIBG myocardial SPECT imaging in heart failure (HF) subjects. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Outcome prediction in heart failure with atrial fibrillation: relative role of left ventricular ejection fraction and neurohormonal measures.

BACKGROUND: 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. METHODS AND RESULTS: 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 < .001, 0.933, P < .001, 0.929, P < .001, 0.916, P < .001, 0.945, P = .001, respectively), but not in AF (1.002, P = .95, 1.060, P = .24, 0.922, P = .15, 0.885, P = .09, 0.932, P = .25). HRs for CAEs and ACM and one or more neurohormonal measures (iodine 123 m-iodobenzylguanidine cardiac parameters, B-type natriuretic peptide, and plasma norepinephrine) were significant in SR and AF. The multivariate models for the first CAE and HFP included neurohormonal measures and LVEF in SR and neurohormonal measures in AF. CONCLUSIONS: In HF with LVEF ≤ 35% with AF, neurohormonal measures, but not LVEF, were related to outcomes.

Measurement of left and right ventricular volumes with tomographic equilibrium radionuclide angiocardiography and cardiac MRI.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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; P<0.001]. Excellent correlations were found between SPECT ERNA and CMRI for combined LV ESV and EDV (R=0.85, P<0.001) and combined RV ESV and EDV (R=0.85, P<0.001). CONCLUSION: This study further validates SPECT ERNA as a method to measure LV and RV EF, ESV, and EDV.

Influence of diabetes mellitus on prognostic utility of imaging of myocardial sympathetic innervation in heart failure patients.

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 <1.6 were independent predictors of heart failure progression, providing incremental prognostic information beyond that available from all other variables. In diabetic subjects, late H/M ratio <1.6 was associated with a 2.99-fold greater 2-year rate of heart failure progression (33.5%) than late H/M ratio ≥1.6 (11.2% event rate). 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.

Symptom improvement after upgrade from right ventricular apical to biventricular pacing: Role of right and left ventricular volumes assessed with single-photon emission computed tomographic equilibrium radionuclide angiocardiography.

BACKGROUND: In patients with heart failure and reduced left ventricular ejection fraction (LVEF), the effect of upgrading from right ventricular (RV) apical to biventricular pacing on RV and left ventricular (LV) volumes and ejection fraction (EF) is unknown. Also, the relationship of symptom improvement after biventricular upgrade to RV and LV volumes and EF has not been clarified. METHODS AND RESULTS: Nineteen patients with long-standing persistent RV apical pacing who had heart failure symptoms and echocardiographic LVEF of 0.40 or less underwent upgrade to biventricular pacing. Patients had single-photon emission computed tomographic equilibrium radionuclide angiocardiography immediately before and at 3-6 months after the upgrade procedure, to measure RV and LV volumes and EF. Biventricular upgrade was associated with increase in LVEF and decrease in LV end-diastolic and end-systolic volumes; right ventricular ejection fraction (RVEF) and end-diastolic and end-systolic volumes were unaltered. Patients with improvement in New York Heart Association heart failure class of I or more had larger initial LV end-diastolic volumes than patients without an improvement and had decreased LV end-diastolic and end-systolic volumes comparatively. Symptom improvement was not associated with RVEF and volume change. CONCLUSION: Symptom improvement with LV remodeling, but not RV remodeling, occurs 3-6 months after biventricular upgrade in patients with heart failure.

Assessment of pulmonary thromboendarterectomy by tomographic electrocardiogram-gated equilibrium radionuclide angiocardiography compared with electron beam computed tomography.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy.

Frequency and determinants of early rapid filling abnormality.

BACKGROUND: The frequency and determinants of early rapid diastolic filling abnormalities in the community and in cardiac patients are poorly understood. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Operator-interactive method for simultaneous measurement of left and right ventricular volumes and ejection fraction by tomographic electrocardiography-gated blood pool radionuclide ventriculography.

BACKGROUND: A method that uses single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) to measure right ventricular (RV) and left ventricular (LV) volumes (in milliliters) and ejection fraction (EF) is described. METHODS AND RESULTS: We recorded 35 paired SPECT ERNA and electron beam computed tomography (EBCT) cardiac studies in 27 patients; for comparison with EBCT, a method for measurement of RV and LV volumes and EF with SPECT ERNA was developed in 18 paired studies and was validated and assessed for reproducibility in 17. Validation indicated that SPECT ERNA and EBCT were similar for measurement of RV volume (end-systolic and end-diastolic volumes in a combined analysis) and EF (180+/-74 mL vs 182+/-80 mL and 0.44+/-0.11 vs 0.43+/-0.11, respectively) and for measurement of LV volume and EF (88+/-36 mL vs 84+/-43 mL and 0.53+/-0.081 vs 0.59+/-0.07, respectively). The SPECT ERNA method was quite reproducible. CONCLUSIONS: RV and LV volumes and EF can be measured readily via SPECT ERNA.

Combined systolic and diastolic dysfunction in the presence of preserved left ventricular ejection fraction.

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<0.0001), PFR increased (2.31+/-0.74, 2.58+/-0.74, 3.15+/-0.94, P<0.0001), PER increased (-2.78+/-0.50, -3.13+/-0.47, -3.83+/-0.84, P<0.0001), the percentages of patients with abnormal PFR decreased (66, 56, 40, P<.0001), and the percentage with abnormal PER decreased (47, 14, 5, P<0.0001). Of 193 patients with preserved LVEF and abnormally low PFR, 65 (34%) had abnormally low PER. CONCLUSIONS: The results indicate that a preserved LVEF was often associated with LV systolic dysfunction (enlarged LV end-systolic volume and low PER) and LV diastolic dysfunction (decreased PFR).

Association of the PURSUIT risk score with predischarge ejection fraction, angiographic severity of coronary artery disease, and mortality in a nonselected, community-based population with non-ST-elevation acute myocardial infarction.

BACKGROUND: 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. METHODS: 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%. RESULTS: 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. CONCLUSIONS: 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.

Usefulness of QRS duration in the absence of bundle branch block as an early predictor of survival in non-ST elevation acute myocardial infarction.

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 duration > or =100 ms and <100 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 QRS > or =100 ms compared with 95.4%, 89.2%, 83.8%, and 74.3%, respectively, in the group with QRS <100 ms (p <0.01, log-rank test). In patients with non-ST elevation AMI, those with QRS duration > or =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 duration <100 ms. After adjusting for age, sex, prior AMI or stroke, heart rate, and Killip class on admission, QRS duration > or =100 ms was independently associated with in-hospital and overall mortality in patients with non-ST elevation AMI. QRS duration > or =100 ms in the absence of BBB is an independent predictor of increased mortality in patients with non-ST elevation AMI.