Clinical performance of Rb-82 myocardial perfusion PET and Tc-99m-based SPECT in patients with extreme obesity.

BACKGROUND: We evaluated the performance of stress imaging with technetium-99m-labeled tetrofosmin single-photon emission computed tomography (SPECT) and rubidium-82 positron emission tomography (PET) in patients with extreme obesity, defined as body mass index ≥40 kg/m2. METHODS: We identified patients with extreme obesity who underwent angiography in our center and either stress SPECT or PET within the previous six months. Cohorts of patients with extreme obesity and a <5% pretest likelihood of CAD who underwent SPECT (N = 25) or PET (N = 25) were also included. RESULTS: In total, 108 patients who underwent SPECT (N = 57) or PET (N = 51) were identified. Scan interpretation was classified as definitely normal or abnormal in 83.3% of PET and 60.5% of SPECT scans, respectively (P < .01). PET demonstrated higher diagnostic accuracy and normalcy rate. PET was found to have higher specificity for the pooled cohort. Similar findings were observed using stenosis cut-offs of ≥50% and ≥70%. CONCLUSIONS: In patients with extreme obesity, PET enabled more definitive scan interpretation with less artifact compared to SPECT. PET provided higher diagnostic accuracy and specificity in the detection of obstructive coronary artery disease.

Long-Term Follow-Up of Outcomes With F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular Dysfunction Secondary to Coronary Disease.

BACKGROUND: Whether viability imaging can impact long-term patient outcomes is uncertain. The PARR-2 study (Positron Emission Tomography and Recovery Following Revascularization) showed a nonsignificant trend toward improved outcomes at 1 year using an F-18-fluorodeoxyglucose positron emission tomography (PET)-assisted strategy in patients with suspected ischemic cardiomyopathy. When patients adhered to F-18-fluorodeoxyglucose PET recommendations, outcome benefit was observed. Long-term outcomes of viability imaging-assisted management have not previously been evaluated in a randomized controlled trial. METHODS AND RESULTS: PARR-2 randomized patients with severe left ventricular dysfunction and suspected CAD being considered for revascularization or transplantation to standard care (n= 195) versus PET-assisted management (n=197) at sites participating in long-term follow-up. The predefined primary outcome was time to composite event (cardiac death, myocardial infarction, or cardiac hospitalization). After 5 years, 105 (53%) patients in the PET arm and 111 (57%) in the standard care arm experienced the composite event (hazard ratio for time to composite event =0.82 [95% confidence interval 0.62-1.07]; P=0.15). When only patients who adhered to PET recommendations were included, the hazard ratio for the time to primary outcome was 0.73 (95% confidence interval 0.54-0.99; P=0.042). CONCLUSIONS: After a 5-year follow-up in patients with left ventricular dysfunction and suspected CAD, overall, PET-assisted management did not significantly reduce cardiac events compared with standard care. However, significant benefits were observed when there was adherence to PET recommendations. PET viability imaging may be best applied when there is likely to be adherence to imaging-based recommendations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00385242.

Comparison of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) in corticosteroid-naive patients with conduction system disease due to cardiac sarcoidosis.

PURPOSE: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population. METHODS: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third-degree AVB). RESULTS: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03). CONCLUSION: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS.

Clinical PET Myocardial Perfusion Imaging and Flow Quantification.

Cardiac PET imaging is a powerful tool for the assessment of coronary artery disease. Many tracers with different advantages and disadvantages are available. It has several advantages over single photon emission computed tomography, including superior accuracy and lower radiation exposure. It provides powerful prognostic information, which can help to stratify patients and guide clinicians. The addition of flow quantification enables better detection of multivessel disease while providing incremental prognostic information. Flow quantification provides important physiologic information, which may be useful to individualize patient therapy. This approach is being applied in some centers, but requires standardization before it is more widely applied.

Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response.

AIMS: We investigated the role of metabolic alterations in the development of a maladaptive right ventricular (RV) response in pulmonary arterial hypertension (PAH), which has not previously been undertaken. This study evaluated relationships between glucose and fatty acid metabolism obtained using PET with invasive pulmonary haemodynamics, RV measurements, and RV function to gain insight into the mechanism of RV maladaptation. METHODS AND RESULTS: Seventeen consecutive PAH patients (mean age 56 ± 15) who underwent right heart catheterization [mean pulmonary arterial pressure (mPAP) 43 ± 12 mmHg] had cardiac 18F-fluoro-2-deoxyglucose (FDG) and (18)F-fluoro-6-thioheptadecanoic acid (FTHA) PET imaging. RV and left ventricular (LV) FDG and FTHA uptake standard uptake values (SUVs) were measured. The SUV was corrected for the partial volume effect (SUVPVE) based on cardiac magnetic resonance imaging (CMR). Right ventricular ejection fraction (RVEF) was determined by CMR. There was a significant positive correlation between mPAP and RV/LV FDG SUVPVE (r = 0.68, P = 0.003), and the ratio of RV/LV FDG SUV : RV/LV FTHA SUV (r = 0.60, P = 0.02). RVEF was negatively correlated with RV/LV FDG SUVPVE uptake (r = -0.56, P = 0.02) and RV/LV FTHA SUVPVE (r = -0.62, P = 0.019). CONCLUSION: Increased pulmonary arterial pressures are associated with increases in the ratio of FDG/FTHA uptake in the RV. Inverse correlation between the uptake of the metabolic tracers and RV function may reflect a shift towards increased fatty acid oxidation and glycolysis associated with RV failure in maladaptive remodelling.

Myocardial viability: it is still alive.

Heart failure presents a significant problem in industrialized countries, with a high prevalence, morbidity, and mortality, where it is most frequently caused by coronary artery disease. Revascularization in patients with symptomatic heart failure has been associated with improved cardiovascular outcomes. Predictors of outcome benefit from revascularization include the presence and extent of hibernating myocardium, ischemia, scar, left ventricular ejection fraction, and renal function. Viability is useful in directing the management of patients with ischemic cardiomyopathy. It is especially useful in those with the highest risk where revascularization decisions are the most difficult. In the absence of definitive prospective randomized data on the benefit of routine viability testing in the management of ischemic cardiomyopathy, physicians will likely continue to use viability testing to assist them with their decision-making process. This review article focuses on the value of viability imaging and the modalities of its measurement, which include PET, SPECT, cardiac MRI, and dobutamine echocardiography. These imaging modalities should be seen as complementary rather than competing methods. In any given clinical setting, the indications, comorbidities, availability, local expertise, sensitivity, specificity, and limitations of each modality need to be considered. When advanced imaging (PET and cardiac MRI) are available, they are generally considered the preferred choice because of their overall higher accuracy. Finally, we explore the role of ischemia in patients with viability and the potential role of neurohormonal and viability imaging in deciding the need for implantable cardiac defibrillator as a primary prevention in patients with severe ischemic cardiomyopathy.

Prognostic value of rubidium-82 positron emission tomography in patients after heart transplant.

BACKGROUND: Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population. METHODS AND RESULTS: Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome. CONCLUSIONS: Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings.

Prevalence of cardiac sarcoidosis in patients presenting with monomorphic ventricular tachycardia.

INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown etiology, which involves the heart in 5-25% of cases. Although ventricular tachycardia (VT) has been reported as the first presentation of sarcoidosis, its prevalence has not previously been investigated. In this prospective study, we sought to systematically investigate the prevalence of cardiac sarcoidosis (CS) in patients presenting with monomorphic VT (MMVT) and no previous history of sarcoidosis. METHODS: Consecutive patients presenting with MMVT to a tertiary care center were screened for inclusion. Patients with idiopathic VT, VT secondary to coronary artery disease, or prior diagnosis of sarcoidosis were excluded. Included patients underwent F-18-fluorodeoxyglucose positron emission tomography (PET) scan. In subjects with PET scanning suggestive of active myocardial inflammation, histological diagnosis was confirmed through extracardiac or endomyocardial biopsy (EMB). RESULTS: A total of 182 patients presented to our institution with VT between February 2010 and September 2012 and 14 subjects met inclusion criteria. Within this group, six of 14 (42%) patients had abnormal PET scans suggesting active myocardial inflammation. Four of the six patients had tissue biopsies that were diagnostic of sarcoidosis; the remaining two patients had guided EMB indicating nonspecific myocarditis. Atrioventricular block was observed in three of four (75%) patients with CS and none in 10 of the others (P = 0.022). Three of the four patients had pulmonary sarcoidosis and one patient had isolated CS. All four patients were treated with corticosteroids. CONCLUSION: In this prospective study, four of 14 (28%) patients presenting with MMVT (without idiopathic VT, ischemic VT, or known sarcoidosis) had CS as the underlying etiology. Clinicians should consider screening for CS in patients with unexplained MMVT.

Is there an association between clinical presentation and the location and extent of myocardial involvement of cardiac sarcoidosis as assessed by ¹8F- fluorodoexyglucose positron emission tomography?

BACKGROUND: Positron emission tomography using (18)F-Fluorodeoxyglucose (FDG) is an emerging modality for diagnosis of cardiac sarcoidosis (CS). We compared the location and degree of FDG uptake in CS patients presenting with either advanced atrioventricular block (AVB) or ventricular tachycardia (VT). METHODS AND RESULTS: We included consecutive patients who presented with either AVB or VT with a diagnosis of CS. A cohort of patients with clinically silent CS was included as controls. FDG activity was quantified as standardized uptake values (SUV) and both the overall mean left ventricular (LV) SUV as well as the Maximum Mean Segmental SUV was recorded for each patient. Receiver operator characteristic (ROC) analysis was performed to identify cutoff SUV values that best identified patients with VT. A total of 27 patients with CS were included (13 females; mean age, 56 ± 8 years; 8 VT, 12 AVB, and 7 controls). Both mean LV SUV and Max SUV in CS patients presenting with VT were significantly higher compared with those with AVB (mean SUV: VT median 5.33, range 4.7-9.35 versus AVB median 2.48, range 0.86-8.59, P=0.016; max SUV: VT median 11.07, range 9.24-14.4 versus AVB median 5.63, range 3.42-15.71, P=0.005) and compared with controls. There was no significant difference in SUV values between AVB patients and controls. ROC analysis for identification of patients with VT showed AUCs of 0.93 and 0.895 for a mean LV SUV of >3.42 and a max SUV >8.56, respectively (P<0.001). CONCLUSIONS: CS patients with VT displayed significantly higher FDG uptake when compared with those with AVB and asymptomatic controls. Further prospective studies are required to evaluate this finding.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial.

BACKGROUND: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging. METHODS/DESIGN: This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry. DISCUSSION: AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies. TRIAL REGISTRATION: NCT01288560.

Current and future clinical applications of cardiac positron emission tomography.

Nuclear imaging, predominantly with single-photon emission tomography, has established and demonstrated value for the assessment of cardiovascular disease (CVD). Formerly, the clinical application of positron emission tomography (PET) was precluded by methodological complexity, high operating costs and lack of widespread availability. However, as PET and radiotracer development technologies have improved and continue to do so, PET is expected to become a mainstay diagnostic cardiovascular imaging modality. Not only is PET imaging of great importance for routine clinical decision-making and diagnosing CVD, it is also gaining prominence in fundamental and translational research models. The scope of this review is to summarize the state-of-the-art advances in PET imaging methodology, clinical utility and potential future application.

Myocardial viability: whom, what, why, which, and how?

Viability imaging might be useful to guide decisions for revascularization in patients with ischemic cardiomyopathy. Recent trial results raise important points for clinicians regarding which modalities to use and in which patients. We discuss the modalities currently used in clinical practice. We suggest that testing be reserved for complex patients in whom the risks and potential benefits from revascularization are highest, and emphasize that the results of viability testing are not the only determinant of potential outcome benefit, and should not be viewed in isolation but as an objective adjunct to decision making.

Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see.

Prodigious efforts and landmark discoveries have led toward significant advances in our understanding of atherosclerosis. Despite significant efforts, atherosclerosis continues globally to be a leading cause of mortality and reduced quality of life. With surges in the prevalence of obesity and diabetes, atherosclerosis is expected to have an even more pronounced impact upon the global burden of disease. It is imperative to develop strategies for the early detection of disease. Positron emission tomography (PET) imaging utilizing [(18)F]fluorodeoxyglucose (FDG) may provide a non-invasive means of characterizing inflammatory activity within atherosclerotic plaque, thus serving as a surrogate biomarker for detecting vulnerable plaque. The aim of this review is to explore the rationale for performing FDG imaging, provide an overview into the mechanism of action, and summarize findings from the early application of FDG PET imaging in the clinical setting to evaluate vascular disease. Alternative imaging biomarkers and approaches are briefly discussed.

Does rubidium-82 PET have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease?: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of rubidium (Rb)-82 positron emission tomography (PET) for the diagnosis of obstructive coronary artery disease (CAD) in comparison to single-photon emission tomography (SPECT). BACKGROUND: Myocardial perfusion imaging is widely used in the assessment of patients with known or suspected CAD. PET using Rb-82 has potential advantages over SPECT that may make it more accurate and that reduce radiation exposure compared with SPECT but has increased costs. Comparisons of these technologies are highly relevant for policy makers and practice guidelines. However, studies directly comparing Rb-82 PET with contemporary SPECT have been limited. METHOD: The authors therefore undertook a systematic review of studies where either Rb-82 PET or technetium-99m SPECT with both attenuation correction and electrocardiography-gating were used as a diagnostic test for obstructive CAD with invasive coronary angiogram as a reference standard. These technologies were then compared. RESULTS: Fifteen PET and 8 SPECT studies (1,344 and 1,755 patients, respectively) met inclusion criteria and pooled accuracy using weighted averages according to the size of the patient population was determined for PET and SPECT with sensitivities of 90% (confidence interval [CI]: 0.88 to 0.92) and 85% (CI: 0.82 to 0.87) and specificities of 88% (CI: 0.85 to 0.91) and 85% (CI: 0.82 to 0.87), respectively. Summary receiver-operating characteristic curves were computed: area under the curve was 0.95 and 0.90 for PET and SPECT, respectively (p < 0.0001). There was heterogeneity among study populations and some studies were limited by referral bias. CONCLUSIONS: Rb-82 PET is accurate for the detection of obstructive CAD and, despite advances in SPECT technology, remains superior. More widespread use of Rb-82 PET may be beneficial to improve CAD detection.

Nuclear perfusion imaging for functional evaluation of patients with known or suspected coronary artery disease: the future is now.

Nuclear imaging, with both single-photon emission computed tomography and PET, has a well-established role in the assessment of patients with known or suspected coronary artery disease. There is a large body of evidence regarding the diagnostic accuracy and prognostic value of these modalities, however, they continue to evolve rapidly with advances in camera and tracer technology, as well as changes in imaging protocols to increase lab efficiency, improve image quality and to decrease radiation exposure to patients. Nuclear imaging also provides insights into atherogenesis at a molecular level and can be combined with other imaging modalities, providing both functional and structural data and complimentary information on the presence of coronary disease and its functional implications.