Left ventricular function and volumes from gated [13N]-ammonia positron emission tomography myocardial perfusion imaging: A prospective head-to-head comparison against CMR using a hybrid PET/MR device.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and volumes obtained simultaneously using [13N]-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard. METHODS AND RESULTS: In this prospective study, 51 patients underwent [13N]-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between [13N]-ammonia-PET and CMR for LVEF was good, with minimal bias (- .6%) and narrow BA limits of agreement (- 7.9% to 6.8%), but [13N]-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (- 11.2 ml), LVEDV (- 28.9 ml), and LVSV (- 17.5 ml). Mean segmental wall motion in [13N]-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01). CONCLUSION: LVEF and LV wall motion can be accurately assessed using [13N]-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device.

BACKGROUND: No methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. METHODS AND RESULTS: Fifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001). CONCLUSION: Similarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis-validation against 13N-ammonia positron emission tomography.

OBJECTIVES: Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI). METHODS: Sixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell's c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%). RESULTS: CAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82-0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively). CONCLUSIONS: CAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone. KEY POINTS: • Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from 13N-ammonia positron emission tomography myocardial perfusion imaging. • CAVi is independently associated with abnormal stress myocardial blood flow. • CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.

Association between reduced brain-derived neurotrophic factor concentration & coronary heart disease.

Background & objectives: Brain-derived neurotrophic factor (BDNF) facilitates neuronal survival, differentiation and synaptic connectivity and affects neurotransmission throughout the brain. However, it has also a modulatory role in energy homeostasis, obesity and cardiovascular function. Obesity, high body mass index (BMI) and dyslipidaemia, among other factors, contribute to coronary heart disease (CHD) development. The exact role of BDNF in development of CHD is not well defined. This study was aimed to evaluate if plasma BDNF concentration was associated with CHD in ethnically homogeneous groups of patients and to correlate plasma BDNF levels with known risk factors for CHD. Methods: Plasma BDNF concentration, BDNF Val66Met polymorphism and other biological and anthropological risk factors for CHD were determined in 208 patients with CHD and 156 healthy controls. Results: Plasma BDNF concentration was significantly (P <0.01) reduced in patients with CHD compared to controls, and it was not influenced by gender, age, smoking or BDNF Val66Met polymorphism. It was considerably correlated with cholesterol (P=0.004), low-density lipoprotein (P=0.006), and diastolic blood pressure (P=0.018) in patients with CHD and with platelet number (P=0.003) in healthy controls. Interpretation & conclusions: The results revealed lower plasma BDNF concentration in patients with CHD, suggesting that decreased plasma BDNF concentration might be associated with CHD pathogenesis. Longitudinal studies with a large sample need to be conducted to confirm these findings.

Validation of deep-learning image reconstruction for coronary computed tomography angiography: Impact on noise, image quality and diagnostic accuracy.

BACKGROUND: Advances in image reconstruction are necessary to decrease radiation exposure from coronary CT angiography (CCTA) further, but iterative reconstruction has been shown to degrade image quality at high levels. Deep-learning image reconstruction (DLIR) offers unique opportunities to overcome these limitations. The present study compared the impact of DLIR and adaptive statistical iterative reconstruction-Veo (ASiR-V) on quantitative and qualitative image parameters and the diagnostic accuracy of CCTA using invasive coronary angiography (ICA) as the standard of reference. METHODS: This retrospective study includes 43 patients who underwent clinically indicated CCTA and ICA. Datasets were reconstructed with ASiR-V 70% (using standard [SD] and high-definition [HD] kernels) and with DLIR at different levels (i.e., medium [M] and high [H]). Image noise, image quality, and coronary luminal narrowing were evaluated by three blinded readers. Diagnostic accuracy was compared against ICA. RESULTS: Noise did not significantly differ between ASiR-V SD and DLIR-M (37 vs. 37 HU, p = 1.000), but was significantly lower in DLIR-H (30 HU, p < 0.001) and higher in ASiR-V HD (53 HU, p < 0.001). Image quality was higher for DLIR-M and DLIR-H (3.4-3.8 and 4.2-4.6) compared to ASiR-V SD and HD (2.1-2.7 and 1.8-2.2; p < 0.001), with DLIR-H yielding the highest image quality. Consistently across readers, no significant differences in sensitivity (88% vs. 92%; p = 0.453), specificity (73% vs. 73%; p = 0.583) and diagnostic accuracy (80% vs. 82%; p = 0.366) were found between ASiR-V HD and DLIR-H. CONCLUSION: DLIR significantly reduces noise in CCTA compared to ASiR-V, while yielding superior image quality at equal diagnostic accuracy.

The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene polymorphism on the efficacy of insulin detemir therapy in patients with type 2 diabetes mellitus.

BACKGROUND: Type II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. Insulin therapy often results in weight gain and does not always ensure adequate glycemic control. However, previous studies reported that insulin detemir is an efficient long-acting insulin with a weight sparing effect. The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the effectiveness of insulin detemir in achieving glucose control and body weight control. Participants and methods: This 52-week observational study included 185 patients with inadequate glycemic control treated with premix insulin analogues, which were replaced with insulin aspart and insulin detemir, and 156 healthy controls. After DNA isolation from blood samples, genotyping of DBH-1021C/T polymorphism (rs1611115) and COMT Val108/158Met polymorphism (rs4680) was performed. RESULTS: Our results confirmed that insulin detemir did not lead to weight gain. The most significant finding was that A carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly better hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No association between DBH-1021C/T genotypes and weight and/or glucose control was detected in diabetes patients or in healthy control subjects. CONCLUSIONS: This study showed that the presence of one or two A allele of the COMT Val108/158Met was associated with improved glycemic response, and with a better response to insulin detemir therapy in patients with type II diabetes, separating them as best candidates for detemir therapy.