Myocardial Washout Research Articles

Usefulness of visual classification for cardiac pathophysiology using count-washout rate map in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. The myocardial WR of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an indicator of myocardial lipolysis, and a decreased WR (<10%) of BMIPP is one of the diagnostic criteria for triglyceride deposit cardiomyovasculopathy (TGCV). However, decreased BMIPP uptake in the early images, as in old myocardial infarction (OMI), would also cause a markedly decreased WR. Since the distinction between these clinical conditions cannot be made based on WR alone, simultaneous evaluation of the counts in the early image and WR is needed to properly understand the cardiac pathophysiology. Purpose To differentiate between TGCV and non-TGCV with OMI, both of which show decreased BMIPP WR, a new Count-WR Map (CWRM) method was evaluated. The purpose is to visually and easily distinguish between the two conditions using CWRM. Methods We introduced a CWRM consisting of two axes: counting in the early image, and WR. The count window was set to a maximum of the mean plus two standard deviations and a minimum of 50 counts, and the WR window was set to a maximum of 30 % and a minimum of -20%. CWRM was visually evaluated as normal, TGCV, non-TGCV with OMI, or TGCV with OMI. Results In normal cases, sufficient counts were observed in the early images, and WR did not decrease; CWRM showed light blue. In TGCV, sufficient counts were observed in the early image, but WRs markedly decreased; CWRM showed even orange. In non-TGCV with OMI, regions with decreased and preserved counts coexisted; CWRM showed light blue in the normal and black in the OMI region. In TGCV with OMI, CWRM showed orange in the TGCV myocardium and black in the OMI region (figure). Conclusions CWRM is useful for visually and easily differentiating TGCV from non-TGCV with OMI. CWRM can be applied to other cardiovascular diseases with count and WR variations for visual classification.

Impaired cardiac sympathetic innervation activity is associated with myocardial extracellular remodeling, functional capacity and biomarkers

Abstract Background Despite recent advances in treatment, heart failure (HF) continues to be associated with high mortality rates. In this setting, 123iodine-meta-iodobenzylguanidine (123I-MIBG) scintigraphy emerges as a promising tool for the prediction of clinical outcomes in HF due to its ability to assess cardiac sympathetic innervation. However, 123I-MIBG scintigraphy's correlation with myocardial remodeling and cardiopulmonary exercise capacity has not yet been fully elucidated. Objectives To evaluate cardiac sympathetic activity through 123I-MIBG scintigraphy, and to analyze its correlation with myocardial remodeling and exercise capacity in HF patients. Methods Symptomatic HF patients (NYHA class II–III) stratified by LVEF as HFpEF (LVEF 45%) and HFrE'F (LVEF <45%) and healthy controls were enrolled. HF patients were euvolemic under optimized treatment at the time of enrollment. All individuals underwent CMR with morphology/function and extracellular volume fraction (ECV) assessment, global longitudinal strain (GLS) by echocardiogram, cardiopulmonary exercise testing (CPET), cardiac sympathetic imaging 123I-MIBG scintigraphy (mIBG), and NT-proBNP. Results Eighty individuals were recruited allocated into the following groups: HFpEF (n=33, 59.42±12.63 years, LVEF: 59.82±9.87, NT-proBNP: 409.40±693.37, H2FPEF-score: 5±2), HFrEF (n=28, 53.93±11.40 years; LVEF: 29.81±8.67, NT-proBNP: 1662,34±2016,73) and healthy controls (42.65±13.96 years, LVEF: 65.27±4.73, NT-proBNP: 44,43±33,28) were enrolled. While ECV was elevated in HF groups (HFpEF: 0.32±0.05%, HFrEF: 0.31±0.41% and controls: 0.26±0.03, p<0.05), adjusted maximum oxygen consumption (VO2max) was markedly reduced vs. controls (HFpEF: 18.58±6.29mL/kg/min, HFrEF: 17.60±3.89mL/kg/min, controls: 29.73±9.98mL/kg/min, p<0.001). The MIBG heart-to-mediastinum ratio at 4 hours (H/M) was significantly lower in HF compared with controls (HFpEF: 1.59±0.25, HFrEF: 1.45±0.15 and controls: 1.92±0.25, p<0.001). Interestingly, the H/M ratio was more impaired with HFrEF compared to HFpEF (Fig. 1A). As a result, the mean myocardial washout rate was increased in HF patients (HFrEF 36.38±14.35, HFpEF 29.92±18.33 vs. controls 8.0±27.01, p<0.001). In addition, considering all HF patients, H/M was inversely associated with ECV (R: −0.45, p<0.001, Fig. 1B), NT-proBNP (R: −0.55, p<0.001) and VO2max (R: −0.27, p: <0.024, Fig. 1C). GLS was inversely associated with H/M in HFrEF but not HFpEF (HFrEF: R: −0.535, p<0.001 and HFpEF: R: −0.036, p=NS, Fig. 1D). Conclusion Cardiac sympathetic activity assessed by 123I-MIBG was abnormal in patients with HF with reduced and preserved EF as compared to controls. H/M, a validated marker for cardiac sympathetic activity, showed a strong correlation with markers of functional capacity and myocardial remodeling. Sympathetic innervation appears to be a limiting factor for global longitudinal strain in HFrEF, while in HFpEF longitudinal strain is independent of sympathetic activity Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The São Paulo Research Foundation

Clinical findings of triglyceride deposit cardiomyovasculopathy

Abstract Background Triglyceride (TG) deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder and was recently encoded as an orphan disease in Europe (ORPHA code: 565612). Defective intracellular lipolysis results in TG accumulation in the myocardium and coronary arteries in TGCV. The myocardial washout rate (WR) of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is an essential indicator to evaluate myocardial lipolysis in vivo, and decreased WR (<10%) of BMIPP is one of the essential items of diagnostic criteria for TGCV. Purpose To clarify clinical findings of TGCV including comorbid conditions and laboratory findings. Methods We enrolled 234 patients who underwent BMIPP scintigraphy between September 2015 and July 2019. The distributions of TGCV in each comorbidity, cardiac functions and laboratory findings were investigated. Results In total, 104 patients were diagnosed with definitive TGCV. The BMIPP WR of TGCV patients was −1.37±10.6%. TGCV patients had various comorbid conditions, including coronary artery disease (75%), diabetes mellitus (56%), and heart failure (21%). Left ventricular ejection fraction (LVEF) of TGCV patients was significantly lower than that of non-TGCV patients (38.1±18.0% vs. 43.6±18.9%, p-value=0.026). Moreover, among those who did not take lipid-lowering drugs, there was no difference in the serum TG level between TGCV and non-TGCV patients (TGCV: n=44, 127±84.6 mg/dL, non-TGCV: n=66, 133±70.7 mg/dL, p-value=0.73). Conclusions TGCV patients showed multiple coexistence of coronary artery disease, diabetes mellitus, or heart failure with lower LVEF. Serum TG level was not significantly different between TGCV and non-TGCV patients. Serum TG did not affect the intracellular TG accumulation in TGCV patients directly, and this result was consistent with the pathophysiological hypothesis that the TG accumulation in the myocardial cytoplasm is due to intracellular lipase dysfunction. Funding Acknowledgement Type of funding sources: None.

Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington’s disease

BackgroundHuntington’s disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). MethodsFifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson’s disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. ResultsWe did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. ConclusionsOur study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

Efficacy of myocardial washout of 99mTc-MIBI/Tetrofosmin for the evaluation of inflammation in patients with cardiac sarcoidosis: comparison with 18F-fluorodeoxyglucose positron emission tomography findings.

Both myocardial perfusion scintigraphy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) are useful for the diagnosis of cardiac sarcoidosis (CS). However, the association between the washout of 99mTc-labeled tracer and FDG PET has not been established. This study aimed to evaluate the association between the washout of 99mTc-labeled tracer and FDG PET findings in patients with CS. We retrospectively analyzed 64 patients (65.0 ± 11.2years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) with 99mTc-labeled tracer and FDG PET. The SPECT images were acquired at 15min (early images) and 3h (delayed images) after injection and scored visually using a 17-segment model with a 5-point scoring system. The washout score was defined as the difference between the early and delayed total defect scores. FDG positivity was considered as focal or focal on diffuse patterns on visual assessment, and FDG uptake was quantified by measuring the standardized uptake value (SUV) of each of the 17 segments. The washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p < 0.001). The washout of 99mTc-labeled tracer can be a useful marker for the evaluation of FDG PET findings in patients with CS.

Influence of antidepressant use on 123I-MIBG heart and lung uptakes in the diagnosis of Lewy body disease

ObjectiveThe clinical significance of decreased physiological lung uptake of 123I-metaiodobenzylguanidine (MIBG) has not been well investigated. This study aimed to elucidate the association between a decrease in lung MIBG uptake with antidepressant intake and the myocardial MIBG uptake in patients who were clinically diagnosed with Lewy body disease (LBD) and patients who were diagnosed as not having LBD.MethodsWe retrospectively reviewed the heart and lung uptakes on 167 consecutive MIBG scans, antidepressant status, and clinical diagnosis of LBD. The images were visually classified into two groups: decreased lung uptake and preserved lung uptake. A semi-quantitative analysis was performed using the heart-to-mediastinum ratio (H/M), lung-to-mediastinum ratio (L/M), and myocardial washout rate (WR).ResultsAll 17 patients with decreased lung uptake were on treated with antidepressants, while none of the 150 patients with preserved lung uptake were treated with any antidepressants. Of the 17 patients with decreased lung uptake, 6 patients were clinically diagnosed as LBD and other 11 were clinically diagnosed as non-LBD. There was not significant difference in early H/M, delayed H/M, and myocardial WR between the 11 non-LBD patients with decreased lung uptake and 83 non-LBD patients with preserved lung uptake (2.87 ± 0.69 vs. 2.89 ± 0.44, 3.09 ± 0.48 vs. 2.98 ± 0.59, and 21.8 ± 11.3% vs. 21.1 ± 12.5%, respectively). Moreover, in LBD patients, there were no significant differences in those values between six patients with decreased lung uptake and 67 patients with preserved lung uptake (1.68 ± 0.32 vs. 1.73 ± 0.42, 1.34 ± 0.21 vs. 1.54 ± 0.57, 46.2 ± 22.8% vs. 42.8 ± 21.3%, respectively).ConclusionsAntidepressants probably blocked MIBG uptake in the lungs, and a decreased lung uptake was not significantly associated with heart uptake. A remarkable decrease in lung uptake can be a signal to check a patient’s medication status.

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Modified Algorithm Using Total Count for Calculating Myocardial Washout Rate in Single-Photon Emission Computerized Tomography.

Background: The arithmetic mean of washout rate (WR) (namely, AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computerized tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. To solve this possible issue, we formulated a modified algorithm for calculating WR based on the total count (namely, TCWR). Methods: The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. Participants included those without cardiovascular diseases (normal), those with CD36 deficiency, triglyceride deposit cardiomyovasculopathy (TGCV), TGCV with old myocardial infarction (OMI), and non-TGCV with OMI. Results: WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4±8.5 and 27.3±8.5% (p=0.97); CD36 deficiency, -3.2±6.5 and -4.1±7.4% (p=0.81); TGCV, 2.4±6.3 and 2.2±6.3% (p=0.93); and TGCV with OMI, -0.9±7.6 and -3.7±8.4% (p=0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8±8.7 and 18.9±6.7%, p=0.0008). Conclusions: TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.

Prognostic value of myocardial MIBG scintigraphy in acute ischemic stroke

Abstract Funding Acknowledgements Type of funding sources: None. Background Autonomic dysfunction is a common complication of acute ischemic stroke and has been associated with poor functional outcome and increased mortality. We investigated the potential relation between the myocardial washout rate (WOR) of 123I-meta-iodobenzylguanidine (123I-mIBG), as a measure of cardiac sympathetic activity, and functional outcome in acute ischemic stroke. Methods 38 patients with ischemic stroke (11 females, 72 years old [61-81)), underwent myocardial 123I-mIBG scintigraphy within the first week after stroke onset. Early (10 minutes post-injection (pi)) and late (4 hours pi) planar scans of the thoracic region were made. Regions of interest (ROI) were drawn over the mediastinum and the heart, and heart-to-mediastinum ratio (HMR) was calculated. Myocardial WOR was calculated as follows: (ROI heart early – ROI heart late)/ (ROI heart early) x 100%. Counts were corrected for background and counts in ROI heart late were corrected for decay. Patients were divided in 2 groups: those with a good functional outcome, defined as modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke (i.e., patient is functionally independent), and those with a poor functional outcome, defined as a mRS &amp;gt; 2. Results Median WOR was 27,4 % (IQR 10,4-43,6). In univariate analysis, poor functional outcome after stroke was associated with age, stroke severity on admission (measured by the National Institutes of Health Stroke Scale (NIHSS)), beta-blocker use before and during hospitalization, WOR and late HMR. In subsequent multivariate analysis WOR (OR 1.087; 95% CI 1.003-1.177, p = 0.042) was an independent predictor of poor stroke outcome even after adjustment for age and NIHSS. Conclusions In patients with acute ischemic stroke, myocardial washout of 123I-mIBG predicts stroke outcome, even after adjustment for age and stroke severity on admission.

Superoxide Dismutase-Loaded Nanoparticles Attenuate Myocardial Ischemia-Reperfusion Injury and Protect Against Chronic Adverse Ventricular Remodeling.

Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia-reperfusion (I/R) injury. Here, nanoparticle-encapsulated SOD (NP-SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome-c assay. In an in vitro I/R model, free and NP-SOD reduce active ROS, preserve mitochondrial integrity and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP-encapsulation of fluorescent-tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP-SOD administration in vivo improves left ventricular contractility at 3-hours post-reperfusion by echocardiography and 4-weeks by echocardiography and invasive pressure-volume catheter analysis. These findings suggest that NP-SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP-SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP-SOD as a therapy to mitigate myocardial I/R injury.

The value of myocardial MIBI washout rate in risk stratification of coronary artery disease

BackgroundAlthough it is well established that MIBI does not redistribute as thallium within the myocardium, it showed a reverse redistribution phenomenon that can be expressed by the rate of myocardial MIBI washout. The aim in this study was calculating the global myocardial washout of the MIBI (GWR) in patients diagnosed with coronary artery disease (CAD) of different risk stratifications.ResultsThis prospective study included 100 patients. All patients were stratified into low-, intermediate-, and high-risk groups according to clinical evaluation using Framingham score, stress ECG results using Duke’s score and finally myocardial perfusion imaging prognostic findings. GWR was estimated in each of these groups. GWR mean was 9.5%, 13%, and 18% within clinically stratified patients into low-, intermediate-, and high-risk patients respectively with correlation coefficient 0.4. In addition, GWR mean was 9.7%, 15.4%, and 18.7% within patients stratified according to exercise ECG findings into low-, intermediate-, and high-risk patients respectively with correlation coefficient 0.6. Combining all myocardial perfusion findings, GWR mean was 7.9%, 15.1%, and 19.3% in patient with low-, intermediate-, and high-risk imaging findings respectively with correlation coefficient 0.71.ConclusionGWR is positively correlated with the risk stratifications of the CAD patients. GWR can be used as an additional parameter to assess the risk of CAD patients.

Correlation Perspectives for the Diagnosis of Idiopathic Triglyceride Deposit Cardiomyovasculopathy

Background: Triglyceride (TG) deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder and was recently encoded as an orphan disease in Europe (ORPHA code: 565612). Defective lipolysis results in TG accumulation in the myocardium and coronary arteries in TGCV. The myocardial washout rate (WR) of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an essential indicator to evaluate myocardial lipolysis in vivo. TGCV is classified into primary and idiopathic type with and without PNPLA2 mutation, respectively. Here, we present the clinical correlation perspectives of TGCV patients in Chiba, Japan, to increase the awareness of this orphan disease and facilitate its diagnosis. Methods: We enrolled 234 patients who underwent BMIPP scintigraphy between September 2015 and July 2019. The diagnosis of TGCV was made based on the criteria we reported previously. Blood smear tests were performed for TGCV classification. The distributions of TGCV in each comorbidity were investigated. Results: In total, 104 patients were diagnosed with definitive idiopathic TGCV (I-TGCV). They had various comorbid conditions, including heart failure with reduced ejection fraction and multivessel coronary artery disease requiring revascularization. Moreover, the serum TG levels in I-TGCV patients were not high, and there was no correlation between serum TG level and BMIPP WR (n=205, p-value=0.31), supporting the pathophysiological hypothesis of TGCV. Conclusion: I-TGCV patients showed multiple coexistence of coronary artery disease, heart failure of unknown etiology, or diabetes mellitus. For patients with such clinical characteristics, BMIPP scintigraphy and calculation of WR should be considered proactively for the diagnosis of TGCV.

Effects of atrial fibrillation on myocardial washout rate of thallium-201 on myocardial perfusion single-photon emission computed tomography.

Myocardial perfusion single-photon emission computed tomography (SPECT) with thallium (Tl)-201 is an established modality for evaluating myocardial ischemia. We assessed the effects of atrial fibrillation (AF) on the myocardial washout rate (WR) of Tl-201 on myocardial perfusion SPECT. A total of 231 patients with no evidence of myocardial ischemia were enrolled retrospectively in this study. Patients were divided into two groups on the basis of the ECG at the time of myocardial perfusion SPECT. The mean myocardial WR of Tl-201 was calculated from the stress and the redistribution Bull's eye maps. There were 34 patients with AF and 197 patients with sinus rhythm. There were no significant differences in clinical variables, except for older age and higher heart rate in patients with AF. Myocardial WR of Tl-201 was significantly lower in patients with AF than those with sinus rhythm (46±12 vs. 51±8%, P=0.03). Multivariate analysis including these factors showed that female sex (β=0.18, P=0.02), AF (β=-0.14 P=0.03), hemoglobin (β=-0.18, P<0.01), and serum creatinine (β=0.24, P<0.01) were determinants of myocardial WR of Tl-201. Our data suggest that AF is associated with reduced myocardial WR of Tl-201 on myocardial perfuison SPECT.

Effects of chronic kidney disease on myocardial washout rate of thallium-201 in patients with normal myocardial perfusion on single photon emission computed tomography.

Myocardial perfusion single photon emission computed tomography (SPECT) is often performed even in patients with chronic kidney disease (CKD). We assessed the effects of CKD on myocardial washout rate (WR) of thallium (Tl)-201 in patients with normal myocardial perfusion on SPECT. Two hundred and fifty-six patients with normal myocardial perfusion were enrolled in this study. CKD was defined as estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2. Patients with eGFR ≥ 60ml/min/1.73m2 were assigned to a control group. The mean myocardial WR of Tl-201 was calculated from the stress and the redistribution Bull's eye maps. With progressive CKD stages, systolic blood pressure and incindence of hypertension were increased. All patients in CKD stage 5 group were being treated with hemodialysis. Myocardial WR of Tl-201 was significantly higher in all of the CKD groups than control group. With progressive CKD stages, myocardial WR of Tl-201 was increased (stage 3, 52.2 ± 9.2%; stage 4, 55.5 ± 8.1%; and stage 5, 58.9 ± 5.6%). Multivariate analysis showed that hemoglobin (β = -0.24, p < 0.001) and eGFR (β = -0.24, p = 0.002) were the major determinants of myocardial WR of Tl-201, but hemodialysis was not. Our data suggest that CKD is associated with increased myocardial WR of Tl-201 in patients with normal perfusion on SPECT.

Effects of hemoglobin level on myocardial washout rate of thallium-201 in patients with normal myocardial perfusion assessed by single-photon emission computed tomography.

Myocardial perfusion single-photon emission computed tomography (SPECT) is often performed even in patients with suspected coronary artery disease complicated by anemia. We assessed the effects of hemoglobin level on myocardial washout rate of Thallium-201 (Tl-201) in patients with normal myocardial perfusion assessed by SPECT. The study population consisted of 231 patients with summed stress score of zero on SPECT. The mean myocardial washout rate of Tl-201 in the left ventricle was calculated from the stress and the redistribution Bull's eye map. Hematological test was performed within 2weeks before gated SPECT. There were 135 male and 96 female patients with a mean age of 72.6 ± 9.0years. The mean hemoglobin was 12.9 ± 1.9mg/dl; the median was 13.2mg/dl and the range was 8.0-16.5mg/dl. There was a significant inverse correlation between hemoglobin level and myocardial washout rate of Tl-201 (r = -0.45, p < 0.001). Univariate linear regression analysis showed that age, female, body mass index, serum creatinine, hemoglobin, end-diastolic volume, and ejection fraction were associated with myocardial washout rate of Tl-201. Multivariate analysis showed that only hemoglobin was the independent predictor of myocardial washout rate of Tl-201 (β = -0.35, p < 0.001). Our data suggested that anemia was a major determinant of increased myocardial washout rate of Tl-201 in patients with normal myocardial perfusion on SPECT.

Novel 99mTc(III) Complexes [99mTcCl(CDO)(CDOH)2B-R] (CDOH2 = Cyclohexanedione Dioxime) Useful as Radiotracers for Heart Imaging.

In this study, we evaluated seven new 99mTc(III) complexes [99mTcCl(CDO)(CDOH)2B-R] (99mTc-2Fboroxime: R = 2-formylfuran-3-yl (2F); 99mTc-3Fboroxime: R = furan-3-yl (3F); 99mTc-5Fboroxime: R = 5-formyfuran-2-yl (5F); 99mTc-HPboroxime: R = 6-hydroxylpyridin-2-yl (HP); 99mTc-MPYboroxime: R = 5-methoxypyridin-3-yl (MPY); 99mTc-PMboroxime: R = 1,5-pyrimidin-3-yl (PM); and 99mTc-4PYboroxime: R = pyridin-4-yl (4PY)) for their potential as heart imaging agents. All new 99mTc(III) radiotracers except 99mTc-2Fboroxime were prepared with high radiochemical purity (RCP > 95%). The low RCP (∼75%) for 99mTc-2Fboroxime is most likely caused by steric hindrance from the 3-formyl group. Biodistribution and imaging studies were performed in SD rats. Planar image quantification was performed to compare their myocardial retention times. We found that the myocardial washout curves of new 99mTc(III) radiotracers were best fitted the biexponential decay function. The AUC (area under the curve) values followed the general trend: 99mTc-5Fboroxime (129 ± 6) > 99mTc-3Fboroxime (114 ± 11) > 99mTc-Teboroxime (104 ± 16) > 99mTc-MPYboroxime (92 ± 18) > 99mTc-4PYboroxime (77 ± 10) > 99mTc-PMboroxime (68 ± 14) ≈ 99mTc-HPboroxime (62 ± 14). The 2 min heart uptake values from biodistribution studies follow the ranking order of 99mTc-5Fboroxime (3.75 ± 0.15%ID/g) ≈ 99mTc-MPYboroxime (3.73 ± 0.24%ID/g) > 99mTc-PMboroxime (3.47 ± 0.15%ID/g) ≈ 99mTc-3Fboroxime ≈ (3.25 ± 0.77%ID/g). The 5 min heart uptake of 99mTc-5Fboroxime (3.91 ± 0.09%ID/g) was almost identical to its 2 min heart uptake (3.75 ± 0.15%ID/g), and its 15 min heart uptake value (2.83 ± 0.08%ID/g) compared well to the 2 min heart uptake of 99mTc-Teboroxime (3.00 ± 0.37%ID/g). It took ∼5 min for 99mTc-5Fboroxime to approach the 1 min heart uptake value of 99mTc-Teboroxime (∼3.5% ID/g) and ∼9.5 min to reach the 2 min heart uptake value of 99mTc-Teboroxime (∼3.0% ID/g). The best image acquisition window is 0-5 min for 99mTc-5Fboroxime. High-quality single-photon emission computed tomography images of the rat hearts were acquired in any of the 5 min window over the first 20 min after its administration. 99mTc-5Fboroxime has significant advantages over 99mTc-Teboroxime as the radiotracer for myocardial perfusion imaging.

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism

IntroductionPARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. ObjectiveNon-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. MethodsThe Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by 123I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). ResultsAmong the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. ConclusionsOur findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease.

Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by (123)I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease.

Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and (123)I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95% confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction.

Myocardial washout rate of resting 99mTc-Sestamibi (MIBI) uptake to differentiate between normal perfusion and severe three-vessel coronary artery disease documented with invasive coronary angiography

Patients with severe coronary artery disease (CAD) may present impaired mitochondrial function to enhance (99m)Tc-sestamibi (MIBI) washout from ischemic myocardium. In this study, we aimed to study the MIBI washout rate (WR) between patients with three-vessel CAD (3V-CAD) confirmed by invasive coronary angiography and healthy normal volunteers (HNV) to evaluate the potential utility of MIBI WR to differentiate between these two populations and to stratify the CAD severity. Ten HNV (male = 5, age = 56 ± 10 years) and eight 3V-CAD patients (male = 4, age = 62 ± 8 years) with 3V lumen stenosis ≥50% were enrolled for this study. Each study subject had a resting MIBI perfusion scan at 90 min and a repeated scan at 4 h post the MIBI injection. Global WR (GWR) and regional WR (RWR) were quantified with the percentage difference of decay-corrected polar maps obtained from the two scans and compared between the HNV and 3V-CAD groups. For the 3V-CAD group, the severity of CAD was assessed with CAD severity scores (CADSS) utilizing degree and location of obstructive lesions (stenosis ≥50%) for quantification and compared with WR to evaluate the correlation between these two variables. Significantly higher GWR was observed in the 3V-CAD (21.1 ± 4.6 %) group than the HNV group (9.5 ± 4.9%) (p < 0.001). RWR values in left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCX) in the 3V-CAD group were also higher than those of the HNV group (LAD 20.7 ± 5.9 vs 9.4 ± 5.6, p < 0.001; RCA 21.3 ± 4.8 vs 9.2 ± 5.8, p < 0.001; LCX 20.5 ± 7.2 vs 10.1 ± 4.4, p = 0.002). Additionally, the linear correlation of GWR and total CADSS for the whole myocardium was strong and statistically significant (y = 0.86x - 1.12, r (2) = 0.73, p = 0.006). Patients with impaired mitochondrial function due to 3V-CAD had consistently higher global and regional rest (99m)Tc-sestamibi washout rates than those of healthy normal volunteers. The global rest (99m)Tc-sestamibi washout rate is a sensitive indicator to stratify the severity of 3V-CAD and to differentiate between severe 3V-CAD and normal perfusion populations.

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

Carvedilol, a nonselective β-blocker, may be more effective than the selective β-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either β-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability. In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the β2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis. (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% ± 3.9% vs. 22.1% ± 2.8%, respectively, P = 0.003), irrespective of β2-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% ± 13% vs. 157% ± 13%, respectively, P = 0.01), irrespective of β2-adrenergic receptor haplotype. Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of β2-receptor haplotype status.