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To evaluate a convolutional neural network's performance (nnU-Net) in the assessment of vascular contours, calcification and PET tracer activity using Ga-68 DOTATATE PET/CT. Patients who underwent Ga-68 DOTATATE PET/CT imaging over a 12-month period for neuroendocrine investigation were included. Manual cardiac and aortic segmentations were performed by an experienced observer. Scans were randomly allocated in ratio 64:16:20 for training, validation and testing of the nnU-Net model. PET tracer uptake and calcium scoring were compared between segmentation methods and different observers. 116 patients (53.5% female) with a median age of 64.5 years (range 23-79) were included. There were strong, positive correlations between all segmentations (mostly r > 0.98). There were no significant differences between manual and AI segmentation of SUV mean for global cardiac (mean ± SD 0.71 ± 0.22 vs. 0.71 ± 0.22; mean diff 0.001 ± 0.008, p > 0.05), ascending aorta (mean ± SD 0.44 ± 0.14 vs. 0.44 ± 0.14; mean diff 0.002 ± 0.01, p > 0.05), aortic arch (mean ± SD 0.44 ± 0.10 vs. 0.43 ± 0.10; mean diff 0.008 ± 0.16, p > 0.05) and descending aorta (mean ± SD < 0.001; 0.58 ± 0.12 vs. 0.57 ± 0.12; mean diff 0.01 ± 0.03, p > 0.05) contours. There was excellent agreement between the majority of manual and AI segmentation measures (r ≥ 0.80) and in all vascular contour calcium scores. Compared with the manual segmentation approach, the CNN required a significantly lower workflow time. AI segmentation of vascular contours using nnU-Net resulted in very similar measures of PET tracer uptake and vascular calcification when compared to an experienced observer and significantly reduced workflow time., (© 2024. Crown.)

Competing Interests: Disclosures Dr Bellinge is supported by a Research Establishment Fellowship from the Royal Australasian College of Physicians Foundation. Dr Tawakol receives research support (to his institution) from Lung Biotechnologies and consulting fees from Cunningham Bounds LLC for unrelated work and is supported by National Institutes of Health (NIH) R01HL152957, R33HL141047, R01HL1495, P01HL131478, R01AR077187, and R01HL16433, and the International Atomic Energy Agency (IAEA) for unrelated work.

Background and Aims: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW)., Methods and Results: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 μg/day), those with the highest intakes (Quartile 4, median 119.3 μg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51-0.86) and CVD mortality (HR 0.61 95%CI 0.41-0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 μg/day., Conclusion: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K 1 are associated with a lower incidence of aortic stenosis., Methods: In the Danish Diet, Cancer and Health study, participants aged 50 to 64 years completed a 192-item food frequency questionnaire at baseline, from which habitual intakes of vitamin K 1 were estimated. Participants were prospectively followed using linkage to nationwide registers to determine incident aortic valve stenosis (primary outcome) and aortic stenosis with subsequent complications (aortic valve replacement, heart failure, or cardiovascular disease-related mortality; secondary outcome)., Results: In 55 545 participants who were followed for a maximum of 21.5 years, 1085 were diagnosed with aortic stenosis and 615 were identified as having subsequent complications. Participants in the highest quintile of vitamin K 1 intake had a 23% lower risk of aortic stenosis (hazard ratio, 0.77 [95% CI, 0.63-0.94]) and a 27% lower risk of aortic stenosis with subsequent complications (hazard ratio, 0.73 [95% CI, 0.56-0.95]), compared with participants in the lowest quintile after adjusting for demographics and cardiovascular risk factors., Conclusions: In this study, a high intake of vitamin K 1 -rich foods was associated with a lower incidence of aortic stenosis and a lower risk of aortic stenosis with subsequent complications., Competing Interests: Disclosures None.

Context: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors., Objective: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes., Methods: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models., Results: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups., Conclusion: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: There is currently no treatment for attenuating progression of arterial calcification. 18 F-sodium fluoride positron emission tomography ( 18 F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K 1 or colchicine affected arterial calcification activity., Methods: 154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K 1 [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K 1 [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on 18 F-NaF PET., Results: 149 subjects completed follow-up (vitamin-K 1 : placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K 1 nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K 1 ., Conclusions: In patients with type 2 diabetes, neither vitamin-K 1 nor colchicine significantly decreases coronary calcification activity, as estimated by 18 F-NaF PET, over a period of 3 months., Clinical Trial Registration: ACTRN12616000024448., (© 2021. American Society of Nuclear Cardiology.)

Background: Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET)., Objectives: We aimed to determine whether vitamin K1 supplementation inhibits arterial calcification activity in individuals with diabetes mellitus., Methods: This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K1 supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K1 supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta., Results: In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K1 supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P = 0.002)., Conclusions: In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis.This trial was registered at anzctr.org.au as ACTRN12616000024448., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Reported associations between vitamin K 1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52-60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K 1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87-192 µg/d) intake of vitamin K 1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K 1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K 1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level., (© 2021. The Author(s).)

Background Dietary vitamin K (K 1 and K 2 ) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K 1 and vitamin K 2 were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K 1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K 2 , the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K 2 intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K 1 or K 2 . The similar inverse associations with both vitamin K 1 and K 2 , despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Purpose of Review: Diabetes mellitus is no longer considered a cardiovascular disease (CVD) risk equivalent, but the optimal methods of risk stratification are a matter of debate. The coronary calcium score (CCS) is a measure of the burden of atherosclerosis and is widely used for CVD risk stratification in the general population. We review recently published data to describe the role of the CCS in people with diabetes mellitus., Recent Findings: People with diabetes mellitus have 10-year event rates for CVD and CVD mortality that are considered high, at a much lower level of CCS than the general population. Different categories of CCS are pertinent to men and women with diabetes mellitus. CCS may be particularly useful in clinical settings when CVD risk is known to be increased but difficult to quantify, for example peri-menopausal women, young persons with diabetes, type 1 diabetic individuals and others. With modern techniques, the radiation dose of a CSS has fallen to levels wherein screening and surveillance could be considered., Summary: The CCS is able to quantify CVD risk in people with diabetes mellitus when there is clinical uncertainty and identifies those with very high event rates. Future research should aim to identify effective risk reduction strategies in this important group., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: 18 F-Sodium Fluoride Positron Emission Tomography ( 18 F-NaF PET) non-invasively detects micro-calcification activity, the earliest stage of atherosclerotic arterial calcification. We studied the association between coronary 18 F-NaF uptake and high-risk plaque features on intra-coronary optical coherence tomography (OCT) and CT-angiography (CTCA) and the potential application to patient-level risk stratification., Methods: Sixty-two prospectively recruited patients with acute coronary syndrome (ACS) underwent multi-vessel OCT, 18 F-NaF PET and CTCA. The maximum tissue to background ratio (TBRmax = standardised uptake value (SUV)max/SUVbloodpool) was measured in each coronary segment on 18 F-NaF PET scans. High-risk plaque features on OCT and CTCA were compared in matched coronary segments. The number of patients testing positive (>2SD above the normal range) for micro-calcification activity was determined., Results: In 62 patients (age, mean ± standard deviation (SD) = 61 ± 9 years, 85% male) the coronary segments with elevated 18 F-NaF uptake had higher lipid arc (LA) (median [25th-75th centile]: 74° [35°-117°] versus 48° [15°-83°], p=0.021), higher prevalence of macrophages [n(%): 37 (62%) versus 89 (39%), p=0.008] and lower plaque free wall (PFW) (50° [7°-110°] versus 94° [34°-180°], p=0.027) on OCT, and a higher total plaque burden (p=0.011) and higher dense calcified plaque burden (p= 0.001) on CTCA, when compared with 18 F-NaF negative segments. Patients grouped by increasing number of coronary lesions positive for microcalcification activity (0,1, ≥2) showed decreasing plaque free wall, increasing calcification and increasing macrophages on OCT (respectively p=0.008, p < 0.001 and p=0.028)., Conclusions: 18 F-NaF uptake is associated with high-risk plaque features on OCT and CTCA in a per-segment and per-patient analysis in subjects hospitalized for ACS., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Objective: The coronary calcium score (CCS) predicts cardiovascular disease risk in individuals with diabetes, and rate of progression of CCS is an additional and incremental marker of risk. 18 F-sodium fluoride positron emission tomography ( 18 F-NaF PET) detects early and active calcifications within the vasculature. We aimed to ascertain the relationship between 18 F-NaF PET activity and CCS progression in patients with diabetes. Approach and Results: We identified individuals between 50 and 80 years with diabetes and no history of clinical coronary artery disease. Those with a CCS ≥10 were invited to undergo 18 F-NaF PET scanning and then repeat CCS >2 years later. 18 F-NaF PET and CCS analysis were performed on a per-coronary and a per-patient level. We compared the proportion of CCS progressors in 18 F-NaF PET-positive versus 18 F-NaF PET-negative coronary arteries. Forty-one participants with 163 coronary arteries underwent follow-up CCS 2.8±0.5 years later. 18 F-NaF PET-positive coronary arteries (n=52) were more likely to be CCS progressors, compared with negative coronary arteries (n=111; 86.5% versus 52.3%, P <0.001). Adjusting for baseline CCS, 18 F-NaF PET-positive disease was an independent predictor of subsequent CCS progression (odds ratio, 2.92 [95% CI, 1.32-6.45], P =0.008). All subjects (100%, 15/15) with ≥2 18 F-NaF-positive coronary arteries progressed in CCS., Conclusions: In subjects with diabetes, 18 F-NaF PET positivity at baseline, independently predicted the progression of calcifications within the coronary arteries 2.8 years later. These findings suggest 18 F-NaF PET may be a promising technique for earlier identification of patients at higher risk of cardiovascular events.

Introduction: 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) is a novel molecular imaging modality with promise for use as a risk stratification tool in cardiovascular disease. There are limitations in the analysis of small and rapidly moving coronary arteries using traditional PET technology. We aimed to validate the use of a motion correction algorithm (eMoco) on coronary 18F-NaF PET outcome parameters., Methods: Patients admitted with an acute coronary syndrome underwent 18F-NaF PET and computed tomography coronary angiography. 18F-NaF PET data were analyzed using a diastolic reconstruction, an ungated reconstruction and the eMoco reconstruction., Results: Twenty patients underwent 18F-NaF PET imaging and 17 patients had at least one positive lesion that could be used to compare PET reconstruction datasets. eMoco improved noise (the coefficient of variation of the blood pool radiotracer activity) compared to the diastolic dataset (0.09 [0.07 to 0.12] vs 0.14[0.11 to 0.17], p < .001) and marginally improved coronary lesion maximum tissue-to-background ratios compared to the ungated dataset (1.33 [1.05 to 1.48]vs 1.29 [1.04 to 1.40], p = .011)., Conclusion: In this pilot dataset, the eMoco reconstruction algorithm for motion correction appears to have potential in improving coronary analysis of 18F-NaF PET by reducing noise and increasing maximum counts. Further testing in a larger patient dataset is warranted.

Cardiovascular disease (CVD) remains a leading cause of death. Preventative therapies that reduce CVD are most effective when targeted to individuals at high risk. Current risk stratification tools have only modest prognostic capabilities, resulting in over-treatment of low-risk individuals and under-treatment of high-risk individuals. Improved methods of CVD risk stratification are required. Molecular imaging offers a novel approach to CVD risk stratification. In particular, 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) has shown promise in the detection of both high-risk atherosclerotic plaque features and vascular calcification activity, which predicts future development of new vascular calcium deposits. The rate of change of coronary calcium scores, measured by serial computed tomography scans over a 2-year period, is a strong predictor of CVD risk. Vascular calcification activity, as measured with 18 F-NaF PET, has the potential to provide prognostic information similar to consecutive coronary calcium scoring, with a single-time-point convenience. However, owing to the rapid motion and small size of the coronary arteries, new solutions are required to address the traditional limitations of PET imaging. Two different methods of coronary PET analysis have been independently proposed and here we compare their respective strengths, weaknesses, and the potential for clinical translation.

Objective: To determine the use of different anticoagulation therapies in rural Western Australia; to establish whether remoteness from health care services affects the choice of anticoagulation therapy; to gather preliminary data on anticoagulation therapy safety and efficacy., Design: Retrospective cohort study of patients hospitalised with a principal diagnosis of atrial fibrillation/flutter (AF) or venous thromboembolism (VTE) during 2014-2015., Setting: Four hospitals serving two-thirds of the rural population of Western Australia., Participants: 609 patients with an indication for anticoagulation therapy recorded in their hospital discharge summary for index admission., Main Outcome Measures: Prescribing rates of anticoagulation therapies by indication for anticoagulation and distance of patient residence from their hospital. The primary safety outcome was re-hospitalisation with a major or clinically relevant non-major bleeding event; the primary lack-of-efficacy outcome was re-hospitalisation for a thromboembolic event., Results: The overall rates of prescription of NOACs and warfarin were similar (34% v 33%). A NOAC was prescribed more often than warfarin for patients with AF (56.0% v 42.2% of those who received an anticoagulant; P < 0.001), but less often for patients with VTE (29% v 48%; P < 0.001). Warfarin was prescribed for 38% of patients who lived locally, a NOAC for 31% (P = 0.013); for non-local patients, the respective proportions were 29% and 36% (P = 0.08). 69% of patients with AF and a CHA2DS2-VASc score ≥ 1 were prescribed anticoagulation therapy. Patients treated with NOACs had fewer bleeding events than patients treated with warfarin (nine events [4%] v 20 events [10%]; P = 0.027)., Conclusions: In rural WA, about one-third of patients with an indication for anticoagulation therapy receive NOACs, but one-third of patients with AF and at risk of stroke received no anticoagulant therapy, and may benefit from NOAC therapy.