Tales from the future-nuclear cardio-oncology, from prediction to diagnosis and monitoring.

Cancer and cardiovascular diseases (CVD) often share common risk factors, and patients with CVD who develop cancer are at high risk of experiencing major adverse cardiovascular events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced non-invasive cardiac imaging has raised great interest in the early detection of CVD and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer-treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments and discuss the specific role of nuclear cardiology alongside other non-invasive imaging techniques.

Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation.

PURPOSE: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of stroke. Indeed, silent AF is frequently identified in unexplained ischemic stroke. 18F-FDG-PET/CT is a powerful tool for assessing myocardial metabolic shift and inflammation, both potentially at stake in AF. This case-control study investigated whether AF could promote FDG uptake in atria after physiological myocardial glucose uptake suppression, and the potential relationship between FDG atrial uptake and prevalence of stroke. METHODS: We retrospectively enrolled 128 patients (64 consecutive patients with AF and 64 without AF as the control group, matched for age and sex) who underwent 18F-FDG-PET/CT after a high-fat low-carbohydrate diet. We analyzed visual and quantitative FDG uptake parameters of the right and left atria (RA/LA) and the right and left appendages (RAA/LAA), and selected clinical features including history of stroke. RESULTS: Diffuse right atrial uptake was present in a third of patients with AF and only two patients in the control group. FDG uptake intensity of both atria was significantly associated with the underlying heart rhythm. The occurrence of stroke was strongly associated with detectable atrial uptake in multivariate analysis, with an odds ratio superior to that of other known risk factors. CONCLUSIONS: This study shows a significant correlation between FDG atrial uptake and AF. While inconsistent, this pattern seems to be associated with an increased prevalence of cardioembolic stroke.

Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers.

PURPOSE: Cardiac involvement in familial transthyretin (TTR) amyloidosis is of major prognostic value, and the development of early-diagnostic tools that could trigger the use of new disease-modifying treatments is crucial. The aim of our study was to compare the respective contributions of 99mTc-diphosphonate scintigraphy (DPD, detecting amyloid deposits) and 123I-MIBG (MIBG, assessing cardiac sympathetic denervation) in patients with genetically proven TTR mutation referred for the assessment of cardiac involvement. METHODS: We prospectively studied 75 consecutive patients (classified as symptomatic or asymptomatic carriers), using clinical evaluation, biomarkers (troponin and BNP), echocardiography, and nuclear imaging. Patients were classified as having normal heart-to-mediastinum (HMR) MIBG uptake ratio 4 h after injection (defined by HM4 ≥ 1.85) or abnormal HM4 < 1.85, and positive DPD uptake (grade ≥ 1 of Perugini classification) or negative DPD uptake. RESULTS: Among 75 patients, 49 (65%) presented with scintigraphic sympathetic cardiac denervation and 29 (39%) with myocardial diphosphonate uptake. When MIBG was normal, DPD was negative except for two patients. Age was an independent predictor of abnormal scintigraphic result of both MIBG and DPD (HR 1.08 and 1.15 respectively), whereas echocardiographic-derived indicators of increased left ventricular filling pressure (E/e' ratio) was an independent predictor of abnormal MIBG (HR 1.33) and global longitudinal strain of positive DPD (HR 1.45). In asymptomatic patients (n = 31), MIBG was abnormal in 48% (n = 15) among whom 50% had a normal DPD; all those with a normal MIBG (n = 16) had a normal DPD. CONCLUSIONS: In TTR mutation carriers, cardiac sympathetic denervation evidenced by decreased MIBG uptake is detected earlier than amyloid burden evidenced by DPD. These results raise the possibility of a diagnostic role for MIBG scintigraphy at an early stage of cardiac involvement in TTR-mutated carriers, in addition to its well-established prognostic value.

Relationship between cardiac microvascular dysfunction measured with 82Rubidium-PET and albuminuria in patients with diabetes mellitus.

BACKGROUND: Albuminuria is of one the strongest predictors of cardiovascular disease (CVD) in diabetes. Diabetes is associated with cardiac microvascular dysfunction (CMD), a powerful, independent prognostic factor for cardiac mortality. The aim of this study was to evaluate the relationship between CMD and microvascular complications in patients without known CVD. METHODS: In this monocentric study, myocardial flow reserve (MFR) was measured with cardiac 82Rubidium positron emission tomography (Rb-PET) in 311 patients referred to nuclear medicine department of Bichat University Hospital for screening of coronary artery disease from 2012 to 2014. Patients with hemodynamically relevant stenosis on coronary angiography or myocardial ischemia on Rb-PET were excluded. Among patients with diabetes, MFR values were compared according to the presence of retinopathy and albuminuria. RESULTS: Overall, 175 patients (118 with type 2 diabetes) were included. MFR was significantly lower in patients with diabetes compared with those without diabetes (2.6 ± 1.1 vs. 3.3 ± 1.7; p < 0.005). In patients with diabetes, MFR decreased progressively in relation to albumin urinary excretion (normoalbuminuria: 2.9 ± 1.1, microalbuminuria: 2.3 ± 1.0, macroalbuminuria: 1.8 ± 0.7; p < 0.0001). MFR was not significantly different in patients with vs. without retinopathy (2.4 ± 1.0 vs. 2.7 ± 1.1, p = 0.07). Microalbuminuria and macroalbuminuria remained strongly associated with impaired MFR after multiple adjustments [odds ratio 2.6 (95% CI 1.1-8.4) and 5.3 (95% CI 1.2-44.7), respectively]. This association was confirmed when analyses were restricted to patients with low levels of coronary calcifications on computed tomography. CONCLUSIONS: Impaired MFR was more frequent in patients with diabetes and was strongly associated with the degree of albuminuria suggesting that CMD and albuminuria might share common mechanisms.

Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.

AIMS: To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients. METHODS AND RESULTS: We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation. Phase images were computed using the first harmonic Fourier transform. Intra-ventricular dyssynchrony was calculated as the delay between the earliest and most delayed 20% of the left ventricular (LV) (IntraV-20/80) and inter-ventricular dyssynchrony as the difference between LV- and right ventricular (RV)-mode phase angles (InterV). Eighty-three patients (57%) were implanted with a CRT device after ERNA. Median follow-up was 35 [21-50] months. Twenty-four events were observed during the first 41 months. Median baseline ERNA dyssynchrony values were 28 [3 to 46] degrees for intraV-20/80 and 9 [-6 to 24] degrees for interV. Comparing survival between CRT and non-CRT patients according to dyssynchrony status, log-rank tests showed no difference in survival in patients with no ERNA dyssynchrony (P = 0.34) while a significant difference was observed in ERNA patients with high level of mechanical dyssynchrony (P = 0.004). CONCLUSION: ERNA mechanical dyssynchrony could be of value in CRT patient selection.

Respective performance of 18F-FDG PET and radiolabeled leukocyte scintigraphy for the diagnosis of prosthetic valve endocarditis.

UNLABELLED: Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of (18)F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of (18)F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. METHODS: (18)F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of (18)F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke-Li IE classification was made after a 3-mo follow-up. RESULTS: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between (18)F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for (18)F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of (18)F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive (18)F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive (18)F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between (18)F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive (18)F-FDG PET results and negative leukocyte scintigraphy results. CONCLUSION: (18)F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than (18)F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive (18)F-FDG PET findings or in the first 2 mo after cardiac surgery.