Relative Prognostic Significance of Positron Emission Tomography Myocardial Perfusion Imaging Markers in Cardiomyopathy.

BACKGROUND: Rubidium-82 positron emission tomography myocardial perfusion imaging provides measurements of perfusion, myocardial blood flow and reserve (MBFR), and changes in left ventricular ejection fraction (LVEF) at rest and peak stress. Although all of these variables are known to provide prognostic information, they have not been well studied in patients with heart failure due to reduced LVEF. METHODS: Between 2010 and 2016, 1255 consecutive unique patients with LVEF≤40% were included in this study who underwent rubidium-82 positron emission tomography myocardial perfusion imaging and did not have subsequent revascularization within 90 days. Perfusion assessment was scored semiquantitatively, and LVEF reserve (stress-rest LVEF) and global MBFR (stress/rest MBF) were quantified using automated software. Cox proportional hazards models adjusted for 14 clinical and 7 test characteristics were used to define the independent prognostic significance of MBFR on all-cause mortality. RESULTS: Of 1255 patients followed for a mean of 3.2 years, 454 (36.2%) died. After adjusting for clinical variables, the magnitude of fixed and reversible perfusion defects was prognostic of death (P=0.02 and 0.01, respectively), while the rest LVEF was not (P=0.18). The addition of LVEF reserve did not add any incremental value, while the addition of MBFR revealed incremental prognostic value (hazard ratio per 0.1 unit decrease in MBFR=1.08 [95% CI, 1.05-1.11], P<0.001) with fixed and reversible defects becoming nonsignificant (P=0.07 and 0.29, respectively). There was no interaction between MBFR and cause of cardiomyopathy (ischemic versus nonischemic). CONCLUSIONS: In patients with a known cardiomyopathy who did not require early revascularization, reduced MBFR as obtained by positron emission tomography myocardial perfusion imaging is associated with all-cause mortality while other positron emission tomography myocardial perfusion imaging measures were not.

Association Between Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography Imaging and Adverse Events in Patients With Autoimmune Rheumatic Disease.

BACKGROUND: Coronary microvascular dysfunction has been described in patients with autoimmune rheumatic disease (ARD). However, it is unknown whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) can predict adverse events in this population. METHODS: Patients with ARD without coronary artery disease who underwent dynamic rest-stress 82Rubidium PET were retrospectively studied and compared with patients without ARD matched for age, sex, and comorbidities. The association between MFR and a composite end point of mortality or myocardial infarction or heart failure admission was evaluated with time to event and Cox-regression analyses. RESULTS: In 101 patients with ARD (88% female, age: 62±10 years), when compared with matched patients without ARD (n=101), global MFR was significantly reduced (median: 1.68 [interquartile range: 1.34-2.05] versus 1.86 [interquartile range: 1.58-2.28]) and reduced MFR (<1.5) was more frequent (40% versus 22%). MFR did not differ among subtypes of ARDs. In survival analysis, patients with ARD and low MFR (MFR<1.5) had decreased event-free survival for the combined end point, when compared with patients with and without ARD and normal MFR (MFR>1.5) and when compared with patients without ARD and low MFR, after adjustment for the nonlaboratory-based Framingham risk score, rest left ventricular ejection fraction, severe coronary calcification, and the presence of medium/large perfusion defects. In Cox-regression analysis, ARD diagnosis and reduced MFR were both independent predictors of adverse events along with congestive heart failure diagnosis and presence of medium/large stress perfusion defects on PET. Further analysis with inclusion of an interaction term between ARD and impaired MFR revealed no significant interaction effects between ARD and impaired MFR. CONCLUSIONS: In our retrospective cohort analysis, patients with ARD had significantly reduced PET MFR compared with age-, sex-, and comorbidity-matched patients without ARD. Reduced PET MFR and ARD diagnosis were both independent predictors of adverse outcomes.

Rubidium-82 Positron Emission Tomography With Intravenous Ergonovine to Diagnose Vasospastic Angina.

The gold standard to diagnose vasospastic angina is intracoronary reactivity testing, which is performed selectively at dedicated centres. Noninvasive imaging with single-photon emission computerized tomography (SPECT) or echocardiography does not enable accurate localization of spasm or quantification of change in myocardial perfusion in response to an abnormal vasoreactivity. Rubidium-82 positron emission tomography myocardial perfusion imaging (82Rb PET-MPI) with intravenous ergonovine was used to diagnose refractory vasospastic angina in a patient with a complex ischemic syndrome, recent coronary stenting, and persistent atypical angina despite maximal tolerable doses of guideline-directed medical therapy.

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model.

PURPOSE: Myocardial blood flow (MBF) estimation with (82)Rubidium ((82)Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. METHODS: Fourteen volunteers underwent imaging with both 3-dimensional (3D) (82)Rb and (15)O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) (82)Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)(whole). Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D (82)Rb MBF was compared with a previously established method. RESULTS: Whole LV correlation of (82)Rb MBF with (15)O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). CONCLUSION: A uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D (82)Rb PET.

Comparison of measures of left ventricular function from electrocardiographically gated 82Rb PET with contrast-enhanced CT ventriculography: a hybrid PET/CT analysis.

UNLABELLED: Because of the ultrashort tracer half-life and high positron energy of (82)Rb, PET images acquired with this tracer are noisier and of lower resolution than those obtained with other PET tracers. The validity of electrocardiographic gating using (82)Rb for assessment of left ventricular (LV) function is not well established. To support feasibility, we compared functional parameters from gated (82)Rb PET with simultaneous high-resolution contrast-enhanced CT ventriculography, obtained as a byproduct a CT coronary angiography during hybrid cardiac PET/CT. METHODS: A total of 24 patients underwent PET/CT, consisting of rest and dipyridamole (82)Rb perfusion studies and contrast-enhanced CT angiography, using a 64-slice scanner, for the workup of coronary artery disease. From gated PET images, LV ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume (ESV) were calculated using 2 commercial products. For functional CT analysis, commercial software using endocardial contour detection was applied. RESULTS: Inter- and intraobserver agreement was good for all methods. On CT, EF was 66% +/- 13%, ESV was 41 +/- 29 mL, and EDV was 115 +/- 36 mL. On PET, EF during dipyridamole was 56% +/- 15% and 52% +/- 15% using the 2 commercial products (P < 0.05 vs. CT), ESV was 36 +/- 28 and 47 +/- 35 mL (P = not significant vs. CT), and EDV was 75 +/- 30 and 91 +/- 33 mL (P < 0.05 vs. CT). Correlations with CT were 0.85 and 0.87 for EF using commercial software, 0.76 and 0.88 for ESV, and 0.60 and 0.68 for EDV (P < 0.01 for all). Bland-Altman analysis confirmed systematic underestimation of EF and EDV by PET versus CT but did not show a significant deviation from linearity. CONCLUSION: Global LV function can be measured reproducibly from gated (82)Rb PET, using different available software products. However, underestimation of EF by (82)Rb PET, compared with CT ventriculography, is present, which is a result of underestimation of EDV from count-poor ED frames. This underestimation needs to be considered for clinical interpretation of (82)Rb PET.

Occupational radiation dose associated with Rb-82 myocardial perfusion positron emission tomography imaging.

BACKGROUND: We determined staff radiation dose during rest and stress rubidium 82 myocardial perfusion positron emission tomography (PET) imaging. METHODS AND RESULTS: Patients received 1,587 +/- 163 MBq (42.9 +/- 4.4 mCi) Rb-82 during rest or pharmacologic stress. A pressurized ion chamber was used to monitor radiation exposure in 50 examinations. For comparison, staff exposure during pharmacologic stress in 20 other patients receiving 1,204 +/- 55.5 MBq (32.54 +/- 1.5 mCi) technetium 99m 2-methoxy isobutyl isonitrile (MIBI) was measured. For Rb-82 infusion and PET acquisition, the mean dose was 0.45 +/- 0.25 microSv (0.045 +/- 0.025 mrem). Exposure for routine stress testing at variable distances from the patient was equivalent to background. Similar exposure for pharmacologic stress testing through 7 minutes after injection of Tc-99m MIBI at variable distances was 1.075 +/- 0.32 microSv (0.108 +/- 0.03 mrem). However, exposure for stress tests starting 7 minutes after Rb-82 infusion at 0.5 m was estimated at 0.4 microSv (0.04 mrem). To determine the potential radiation dose for those responding to a medical emergency or otherwise in close proximity to a patient, we measured the mean cumulative dose at 0.5 m from 0 to 7 minutes of Rb-82 infusion, which resulted in 19.1 +/- 5.8 microSv (1.9 +/- 0.58 mrem). CONCLUSIONS: Radiation doses for all tasks during routine Rb-82 stress-rest PET are lower than measured Tc-99m MIBI values. However, the radiation dose in close proximity to the patient during or immediately after Rb-82 infusion can be considerably higher, underscoring the need for strict attention to source distance and contact times.

Swelling-activated K+ efflux and regulatory volume decrease efficiency in human bronchial epithelial cells.

This study describes the correlation between cell swelling-induced K+ efflux and volume regulation efficiency evaluated with agents known to modulate ion channel activity and/or intracellular signaling processes in a human bronchial epithelial cell line, 16HBE14o(-1). Cells on permeable filter supports, differentiated into polarized monolayers, were monitored continuously at room temperature for changes in cell height (T(c)), as an index of cell volume, whereas (86)Rb efflux was assessed for K+ channel activity. The sudden reduction in osmolality of both the apical and basolateral perfusates (from 290 to 170 mosmol/kg H(2)O) evoked a rapid increase in cell volume by 35%. Subsequently, the regulatory volume decrease (RVD) restored cell volume almost completely (to 94% of the isosmotic value). The basolateral (86)Rb efflux markedly increased during the hyposmotic shock, from 0.50 +/- 0.03 min(-1) to a peak value of 6.32 +/- 0.07 min(-1), while apical (86)Rb efflux was negligible. Channel blockers, such as GdCl(3) (0.5 mM), quinine (0.5 mM) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB, 100 microM), abolished the RVD. The protein tyrosine kinase inhibitors tyrphostin 23 (100 microM) and genistein (150 microM) attenuated the RVD. All agents decreased variably the hyposmosis-induced elevation in (86)Rb efflux, whereas NPPB induced a complete block, suggesting a link between basolateral K(+) and Cl(-1) efflux. Forskolin-mediated activation of adenylyl cyclase stimulated the RVD with a concomitant increase in basolateral (86)Rb efflux. These data suggest that the basolateral extrusion of K+ and Cl(-1) from 16HBE14o(-1) cells in response to cell swelling determines RVD efficiency.