Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension.

Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH. Methods: We enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined. Results: Individuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL, p<0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain (R=-0.43, p=0.02 and R=-0.37, p=0.05 respectively), RV fractional area change (R=0.51, p<0.01 and R=0.48, p<0.01 respectively), RV end-systolic area (R=-0.63, p<0.001 and R=-0.48, p<0.01 respectively), RV end-diastolic area: R=-0.58, p<0.001 and R=-0.41, p=0.03 respectively), and RV glucose uptake by PET (R=-0.46, p=0.01 and R=-0.30, p=0.10 respectively). NT-proBNP was negatively correlated with TC (R=-0.61, p=0.01) and TG (R=-0.62, p<0.02) in PH. Conclusion: These findings confirm dyslipidemia is associated with worse right ventricular function in PH.

Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial.

BACKGROUND: Right-sided heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Similar to left heart failure, sympathetic overactivation and ß-adrenoreceptor (ßAR) abnormalities are found in PAH. Based on successful therapy of left heart failure with ß-blockade, the safety and benefits of the nonselective ß-blocker/vasodilator carvedilol were evaluated in PAH. METHODS: PAH Treatment with Carvedilol for Heart Failure (PAHTCH) is a single-center, double-blind, randomized, controlled trial. Following 1-week run-in, 30 participants were randomized to 1 of 3 arms for 24 weeks: placebo, low-fixed-dose, or dose-escalating carvedilol. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Decreases in heart rate and blood pressure with carvedilol were well tolerated; heart rate correlated with carvedilol dose. Carvedilol-treated groups had no decrease in exercise capacity measured by 6-minute walk, but had lower heart rates at peak and after exercise, and faster heart rate recovery. Dose-escalating carvedilol was associated with reduction in right ventricular (RV) glycolytic rate and increase in ßAR levels. There was no evidence of RV functional deterioration; rather, cardiac output was maintained. CONCLUSIONS: Carvedilol is likely safe in PAH over 6 months of therapy and has clinical and mechanistic benefits associated with improved outcomes. The data provide support for longer and larger studies to establish guidelines for use of ß-blockers in PAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT01586156FUNDING. This project was supported by NIH R01HL115008 and R01HL60917 and in part by the National Center for Advancing Translational Sciences, UL1TR000439.

Metabolic and Functional Evaluation of the Heart and Lungs in Pulmonary Hypertension by Gated 2-[18F]-Fluoro-2-deoxy-D-glucose Positron Emission Tomography.

Pulmonary hypertension (PH) is associated with a metabolic shift towards glycolysis in both the right ventricle and lung. This results in increased glucose uptake to compensate for the lower energy yield of glycolysis, which creates a potential for 2-[18F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to be a useful tool in the evaluation of participants with PH. We investigated the utility of PET for PH by comparing FDG-PET uptake in the right ventricle and lungs in 30 participants with PH and eight healthy controls and correlating these measurements with echocardiographic (ECHO) measurements and other traditional assessments commonly used in PH. All participants underwent gated FDG-PET scanning in the fasting state, ECHO, six-minute walk test (6MWT), and blood draw for NT-proBNP. Participants also completed the CAMPHOR questionnaire. Right ventricular (RV) end-diastolic and end-systolic volumes, RV ejection fraction, and FDG uptake by PET were significantly different between PH and healthy controls and strongly correlated with plasma NT-proBNP levels and RV ECHO parameters including TAPSE, RV systolic pressure, Tei index, and global peak systolic strain. In addition, lung standardized uptake value (SUV) was also found to be significantly higher in participants with PH than healthy controls. However, lung SUV did not show any significant correlations with NT-proBNP levels, 6MWT, or functional and pressure measurements by ECHO. In this study, we demonstrated the ability to evaluate both lung and right heart metabolism and function in PH by using a single gated FDG-PET scan.

Transmission Imaging in Lymphoscintigraphy with a 153Gd Flood Source.

UNLABELLED: Lymphoscintigraphy uses intradermal or interstitial injections of (99m)Tc-labeled tracers to produce images of focal lymph nodes. Because there is little or no anatomic information in the (99m)Tc images, a (57)Co flood source is sometimes used to provide transmission data along with the emission data. The anatomic shadow from the transmission scan generally improves interpretation and surgical planning. However, the (57)Co transmission photons contribute to background on the (99m)Tc images, reducing contrast and signal-to-noise ratio (SNR). SNR is related to lesion detection, and some lymph nodes that would be detected in an emission-only scan might not be detected if acquired with a (57)Co flood source. An alternative to a (57)Co flood source is a (153)Gd flood source, which has primary photon emissions well below the (99m)Tc emission window, allowing the shadow to be acquired in a separate transmission window. Significantly smaller crosstalk from (153)Gd should improve SNR and therefore would be expected to improve lymph node detection. We hypothesized that the use of a (153)Gd flood source would reduce background and improve SNR for these studies. METHODS: Phantom studies simulating lymphoscintigraphy were performed to compare performance with a (153)Gd flood source, a (57)Co flood source, and no flood source. SNR in the (99m)Tc emission images was measured using a water phantom to simulate patient body and point sources of various activities to simulate nodes and injection site. The encouraging phantom studies prompted use of the (153)Gd flood source in routine clinical breast lymphoscintigraphy, melanoma lymphoscintigraphy, and lymphedema studies. Because emission and transmission data were acquired in separate energy windows, fused planar images of emission and transmission data were available to the physician. RESULTS: SNR was highest with no flood source and was lowest with the (57)Co flood source by a significant margin. SNR with the (153)Gd flood source was similar to that with no flood source on the anterior (transmission) view. SNR was reduced somewhat in the posterior (nontransmission) view because of attenuation of signal by the flood source itself. Minor crosstalk in the (99m)Tc window was observed with the (153)Gd flood source, attributed to simultaneous detection of x-ray photons and gamma-photons. This crosstalk was reduced by introducing thin metal filters to absorb most x-ray photons, at the expense of more attenuation in the posterior view. Unlike with the (57)Co flood source, a usable posterior view (with anatomic shadow derived from the anterior view) was generated with the (153)Gd flood source. Clinical lymphoscintigraphy images with the (153)Gd flood source were of high quality. Interpretation was aided by the ability to control image mixing and brightness and contrast of separate color scales. CONCLUSION: By producing fused images with reduced crosstalk and improved image quality, a (153)Gd flood source offers advantages over a conventional (57)Co flood source for anatomic shadowing in lymphoscintigraphy. Lymph nodes in emission images have higher SNR, indicating a likely improvement in clinical lesion detection. Separate emission and transmission images provide additional flexibility in image display during interpretation.

Prediction of survival by [18F]fluorodeoxyglucose positron emission tomography in patients with locally advanced non-small-cell lung cancer undergoing definitive chemoradiation therapy: results of the ACRIN 6668/RTOG 0235 trial.

PURPOSE: In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models. RESULTS: Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak. CONCLUSION: Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year.

BACKGROUND: The development of tools to monitor the right ventricle in pulmonary arterial hypertension (PAH) is of clinical importance. PAH is associated with pathologic expression of the transcription factor hypoxia-inducible factor (HIF)-1α, which induces glycolytic metabolism and mobilization of proangiogenic progenitor (CD34(+)CD133(+)) cells. We hypothesized that PAH cardiac myocytes have a HIF-related switch to glycolytic metabolism that can be detected with fasting 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography (FDG-PET) and that glucose uptake is informative for cardiac function. METHODS: Six healthy control subjects and 14 patients with PAH underwent fasting FDG-PET and echocardiogram. Blood CD34(+)CD133(+) cells and erythropoietin were measured as indicators of HIF activation. Twelve subjects in the PAH cohort underwent repeat studies 1 year later to determine if changes in FDG uptake were related to changes in echocardiographic parameters or to measures of HIF activation. MEASUREMENTS AND RESULTS: FDG uptake in the right ventricle was higher in patients with PAH than in healthy control subjects and correlated with echocardiographic measures of cardiac dysfunction and circulating CD34(+)CD133(+) cells but not erythropoietin. Among patients with PAH, FDG uptake was lower in those receiving ß-adrenergic receptor blockers. Changes in FDG uptake over time were related to changes in echocardiographic parameters and CD34(+)CD133(+) cell numbers. Immunohistochemistry of explanted PAH hearts of patients undergoing transplantation revealed that HIF-1α was present in myocyte nuclei but was weakly detectable in control hearts. CONCLUSIONS: PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.

Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial.

UNLABELLED: Although (123)I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of (123)I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma. METHODS: A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of (123)I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up. RESULTS: Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), (123)I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity. CONCLUSION: This prospective study demonstrated a sensitivity of 82%-88% and specificity of 82%-84% for (123)I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.

Preoperative 123I/99mTc-sestamibi subtraction SPECT and SPECT/CT in primary hyperparathyroidism.

UNLABELLED: The trend toward focused surgical parathyroidectomy requires precise preoperative localization of parathyroid lesions in patients with hyperparathyroidism. The purpose of this study was to directly compare the diagnostic accuracy of (99m)Tc-sestamibi/(123)I subtraction SPECT with SPECT/CT for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism. METHODS: A total of 61 consecutive surgical patients with primary hyperparathyroidism underwent both (123)I/(99m)Tc-sestamibi subtraction SPECT and SPECT/CT scans preoperatively, using a hybrid SPECT/CT instrument that combined a dual-detector SPECT camera with a 6-slice multidetector spiral CT scanner. Four hours after being given (123)I-sodium iodide orally, each patient received (99m)Tc-sestamibi intravenously, followed immediately by a simultaneous, dual-isotope SPECT scan of the neck and upper chest. Then, without moving the patient, we performed a non-contrast-enhanced CT scan of the same body region. Normalization and subtraction of the (123)I SPECT images from the (99m)Tc SPECT images were performed. The subtraction SPECT and the coregistered fused SPECT/CT studies were interpreted separately, with images scored on a 5-point scale. Surgical and histopathologic findings were used as the standard of comparison. RESULTS: Surgery was successful in 57 patients (solitary parathyroid adenoma in 48 patients, double parathyroid adenomas in 6 patients, and 10 hyperplastic parathyroid glands in 3 patients). The sensitivities of SPECT (50/70 = 71%) and SPECT/CT (49/70 = 70%) were similar (P = 0.779). The specificity of SPECT/CT (26/27 = 96%) was significantly greater than that of SPECT (13/27 = 48%; P = 0.006). The receiver-operating-characteristic area under the curve of SPECT/CT (0.833) was significantly greater than that of SPECT (0.632; P < 0.001). CONCLUSION: SPECT/CT is significantly more specific than dual-isotope subtraction SPECT for the preoperative identification of parathyroid lesions in patients with primary hyperparathyroidism.

SPECT/CT imaging: clinical utility of an emerging technology.

Single-photon emission computed tomography (SPECT) has been a mainstay of nuclear medicine practice for several decades. More recently, combining the functional imaging available with SPECT and the anatomic imaging of computed tomography (CT) has gained more acceptance and proved useful in many clinical situations. Most vendors now offer integrated SPECT/CT systems that can perform both functions on one gantry and provide fused functional and anatomic data in a single imaging session. In addition to allowing anatomic localization of nuclear imaging findings, SPECT/CT also enables accurate and rapid attenuation correction of SPECT studies. These attributes have proved useful in many cardiac, general nuclear medicine, oncologic, and neurologic applications in which the SPECT results alone were inconclusive. Optimal clinical use of this rapidly emerging imaging modality requires an understanding of the fundamental principles of SPECT/CT, including quality control issues as well as potential pitfalls and limitations. The long-term clinical and economic effects of this technology have yet to be established.

PET and PET/CT imaging: what clinicians need to know.

Positron emission tomography (PET), once the sole province of academic medical centers, is rapidly being adopted in daily clinical practice in community hospitals and outpatient centers. It can be especially useful in oncology, cardiology, and neurology. We provide an overview of the fundamentals of PET and PET with computed tomography (PET/CT) and discuss their current clinical utility.

FDG positron emission tomography/computerized tomography features of bleomycin-induced pneumonitis.

Bleomycin is a widely used chemotherapeutic that has been shown to induce life-threatening interstitial lung disease in a small subset of patients. We report a case of bleomycin-induced pneumonitis in a patient treated for Hodgkin lymphoma with severe clinical respiratory symptoms, a marked restrictive pattern on pulmonary function tests, and FDG avid lymphadenopathy and diffuse increased uptake involving both lungs on imaging. To our knowledge, the in-line computed tomography/18F-fluorodeoxyglucose positron emission tomography of bleomycin induced pneumonitis has not been previously reported in the literature.