Consistent tracer administration profile improves test-retest repeatability of myocardial blood flow quantification with 82Rb dynamic PET imaging.

OBJECTIVES: Quantification of myocardial blood flow (MBF) and stress/rest flow reserve is used increasingly to diagnose multi-vessel coronary artery disease and micro-vascular disease with PET imaging. However, variability in the measurements may limit physician confidence to direct revascularization therapies based on specific threshold values. This study evaluated the effects of rubidium-82 (82Rb) tracer injection profile using a constant-activity-rate (CA) vs a constant-flow-rate (CF) infusion to improve test-retest repeatability of MBF measurements. METHOD: 22 participants underwent single-session 82Rb dynamic PET imaging during rest and dipyridamole stress using one of 2 test-retest infusion protocols: CA-CA (n = 12) or CA-CF (n = 10). MBF was quantified using a single-tissue-compartment model (1TCM) and a simplified retention model (SRM). Non-parametric test-retest repeatability coefficients (RPCnp) were compared between groups. Myocardium-to-blood contrast and signal-to-noise ratios of the late uptake images (2 to 6 minutes) were also compared to evaluate standard myocardial perfusion image (MPI) quality. RESULTS: MBF values in the CA-CA group were more repeatable (smaller RPCnp) than the CA-CF group using the 1TCM at rest alone, rest and stress combined, and stress/rest reserve (21% vs 36%, 16% vs 19%, and 20% vs 27%, P < 0.05, respectively), and using the SRM at Rest and Stress alone, Rest and Stress combined, and stress/rest reserve (21% vs 38%, 15% vs 25%, 22% vs 38%, and 23% vs 49%, P < 0.05, respectively). In terms of image quality, myocardium-to-blood contrast and signal-to-noise ratios were not significantly different between groups. CONCLUSIONS: Constant-activity-rate 'square-wave' infusion of 82Rb produces more repeatable tracer injection profiles and decreases the test-retest variability of MBF measurements, when compared to a constant-flow-rate 'bolus' administration of 82Rb, especially with SRM, and without compromising standard MPI quality.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

BACKGROUND: Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. METHODS AND RESULTS: Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). CONCLUSIONS: In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.

Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging.

BACKGROUND: Rubidium-82 ((82)Rb) PET imaging has been proposed for routine myocardial blood flow (MBF) quantification. However, few studies have investigated the test-retest repeatability of this method. The aim of this study was to optimize same-day repeatability of rest MBF imaging with a highly automated analysis program (FlowQuant) using image-derived input functions and dual spillover corrections (SOC). METHODS: Test-retest repeatability of resting left-ventricle (LV) MBF was measured in patients (n = 27) with suspected coronary artery disease (CAD) and healthy volunteers (n = 9). The effects of scan-time, reconstruction, and quantification methods were assessed with correlation and Bland-Altman repeatability coefficients. RESULTS: Factors affecting rest MBF included gender, suspected CAD, and SOC (P < .001). Significant test-retest correlations were found using all analysis methods tested (r > 0.79). The best repeatability coefficient for same-day MBF was 0.20 mL/minute/g using a 6-minute scan-time, iterative reconstruction, SOC, resting rate-pressure-product (RPP) adjustment, and left atrium input function. This protocol was significantly less variable than standard protocols using filtered back-projection reconstruction, longer scan-time, no SOC, or LV input function. CONCLUSION: Absolute MBF can be measured with good repeatability using FlowQuant analysis of (82)Rb PET scans with a 6-minute scan time, iterative reconstruction, dual SOC, RPP-adjustment, and an image-derived input function in the left atrium cavity.

Does quantification of myocardial flow reserve using rubidium-82 positron emission tomography facilitate detection of multivessel coronary artery disease?

BACKGROUND: Relative myocardial perfusion imaging (MPI) is the standard imaging approach for the diagnosis and prognostic work-up of coronary artery disease (CAD). However, this technique may underestimate the extent of disease in patients with 3-vessel CAD. Positron emission tomography (PET) is also able to quantify myocardial blood flow. Rubidium-82 ((82)Rb) is a valid PET tracer alternative in centers that lack a cyclotron. The aim of this study was to assess whether assessment of myocardial flow reserve (MFR) measured with (82)Rb PET is an independent predictor of severe obstructive 3-vessel CAD. METHODS: We enrolled a cohort of 120 consecutive patients referred to a dipyridamole (82)Rb PET MPI for evaluation of ischemia neither with prior coronary artery bypass graft nor with recent percutaneous coronary intervention that also underwent coronary angiogram within 6 months of the PET study. Patients with and without 3-vessel CAD were compared. RESULTS: Among patients with severe 3-vessel CAD, MFR was globally reduced (<2) in 88% (22/25). On the adjusted logistic Cox model, MFR was an independent predictor of 3-vessel CAD [.5 unit decrease, HR: 2.1, 95% CI (1.2-3.8); P = .015]. The incremental value of (82)Rb MFR over the SSS was also shown by comparing the adjusted SSS models with and without (82)Rb MFR (P = .005). CONCLUSION: (82)Rb MFR is an independent predictor of 3-vessel CAD and provided added value to relative MPI. Clinical integration of this approach should be considered to enhance detection and risk assessment of patients with known or suspected CAD.

Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia.

OBJECTIVES: We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 ((82)Rb) positron emission tomography (PET) in patients assessed for ischemia. BACKGROUND: The clinical value of MFR quantification using (82)Rb PET beyond relative myocardial perfusion imaging remains uncertain. METHODS: We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. RESULTS: For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). CONCLUSIONS: MFR quantified using (82)Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of (82)Rb PET-quantified MFR could improve risk stratification for patients being investigated for ischemia.

Relation between right ventricular function and increased right ventricular [18F]fluorodeoxyglucose accumulation in patients with heart failure.

BACKGROUND: Left heart failure is characterized by alterations in metabolic substrate utilization, and metabolic modulation may be a future strategy in the management of heart failure. Little is known about cardiac metabolism in the right ventricle and how it relates to other measures of right ventricular (RV) function. This study was designed to measure glucose metabolism in the right ventricle, as estimated by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography imaging and to determine the relation between RV function and FDG uptake in patients with heart failure. METHODS AND RESULTS: A total of 68 patients underwent cardiac [(18)F]FDG positron emission tomography scanning with measurement of RV FDG uptake as a standardized uptake value. Perfusion imaging was acquired at rest with rubidium-82 or [(13)N]ammonia. RV function was determined by equilibrium radionuclide ventriculography. Relative RV FDG uptake was determined as the ratio of RV to LV standardized uptake value. Fifty-five percent of these patients had ischemic cardiomyopathy. The mean LV and RV ejection fractions were 21±7% and 35±10%, respectively. There was a correlation between RV ejection fraction and the ratio of RV to LV FDG uptake whether the entire LV myocardium (r=-0.40, P<0.001) or LV free wall (r=-0.43, P<0.001) was used. This relation persisted in the subgroup with nonischemic cardiomyopathy (r=-0.37, P=0.04). RV FDG uptake was weakly related to increased RV systolic pressure but not related to LV size, function, or FDG uptake. The correlation between RV ejection fraction and RV/LV FDG was maintained after partial-volume correction (r=-0.68, P<0.001). CONCLUSIONS: RV dysfunction is associated with an increase in RV FDG uptake, the magnitude of which may be correlated with severity.

Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program.

BACKGROUND: Changes in myocardial blood flow between rest and stress states are commonly used to diagnose coronary artery disease. Relative myocardial perfusion imaging (MPI) is used routinely while myocardial blood flow quantification (MBF) may improve the sensitivity for detection of early disease. The ratio of flow at stress and rest (S/R) and their difference (S-R) have both been proposed as a means to detect regions with reduced myocardial flow reserve (MFR). In this study, we describe a highly automated method to calculate regional and global rest, stress, S/R, and S-R polar maps of the left ventricle myocardium. METHODS: We measured the inter- and intra-operator variability using two randomized datasets (n = 30 each) for each of two operators (novice and expert) with correlation and Bland-Altman reproducibility coefficient (RPC%) analyses. RESULTS: S-R MBF had less inter-operator dependent variability than S/R (RPC% = 5.0% vs 12.6%, P < .001). While there was no difference in intra-operator variability with S-R MBF (novice vs expert RPC% = 6.4% vs 5.9%, P = ns), variability was higher in the novice-operator for S/R (RPC% = 16.8% vs 8.5% respectively, P < .001), suggesting that S-R may be preferred for detecting small changes in MFR. The novice operator's intervention pattern became more similar to that of the expert in the later dataset, emphasizing the need for adequate training and quality assurance. CONCLUSION: The proposed method results in low operator-dependent variability, suitable for routine use.