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Focused, low tube potential, coronary calcium assessment prior to coronary CT angiography: A prospective, randomized clinical trial.
Crimm, HA, Fergestrom, NM, Dye, C, Philip, C, Nguyen, BT, Villines, TC
Journal of cardiovascular computed tomography. 2021;(3):240-245
Abstract
BACKGROUND Coronary artery calcium (CAC) scanning is commonly performed before coronary CT angiography (CTA) based partly on its potential to influence CTA scan parameters. Encompassing the whole heart and performed at high tube potential (120 kVp), standard (Agatston) CAC scanning adds to patient radiation exposure. Most CAC exists in the proximal and mid coronary segments and is easily visualized at low kVp. METHODS We tested the impact of a modified calcium scan on coronary CTA acquisition decision-making and image quality in a randomized clinical trial. Providers documented planned CTA acquisition parameters prior to CAC scanning in a blinded manner. Standard Agatston CAC scans proceeded in typical fashion whereas modified scans utilized 80 kVp and reduced z-axis length focused on the proximal-to-mid coronary arteries. CTA providers reviewed the CAC burden then documented final acquisition parameters. RESULTS The study included 172 patients (48% female; mean age 59 ± 6.7). As planned, the calcium scan effective dose was significantly lower in the modified CAC scan group (0.14 vs. 0.74 mSv using a 0.014 k-factor or 0.26 vs. 1.38 mSv using a 0.026 k-factor; both p < 0.001). Initially selected CTA parameters were changed at an identical rate following visual CAC assessment (59%). There was no significant difference in coronary CTA image quality (median quality score = 4 in both groups, p = 0.26), noise (31.0 vs 31.4 HU; p = 0.81), or signal/noise ratio (17.9 vs 16.8; p = 0.26). CONCLUSIONS A low-kVp scan with focused field-of-view provides actionable information regarding the presence and severity of CAC prior to coronary CTA. Coronary CTA parameters based on patient variables are frequently modified after assessing CAC burden in the CTA suite. CLINICALTRIALS. GOV REGISTRATION NUMBER NCT02972242.
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A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD).
Toussaint, ND, Pedagogos, E, Lioufas, NM, Elder, GJ, Pascoe, EM, Badve, SV, Valks, A, Block, GA, Boudville, N, Cameron, JD, et al
Journal of the American Society of Nephrology : JASN. 2020;(11):2653-2666
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BACKGROUND Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. METHODS To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. RESULTS A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. CONCLUSIONS In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Australian Clinical Trials Registry, ACTRN12610000650099.
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Citric-acid dialysate improves the calcification propensity of hemodialysis patients: A multicenter prospective randomized cross-over trial.
Ter Meulen, KJ, Dekker, MJE, Pasch, A, Broers, NJH, van der Sande, FM, van der Net, JB, Konings, CJAM, Gsponer, IM, Bachtler, MDN, Gauly, A, et al
PloS one. 2019;(12):e0225824
Abstract
INTRODUCTION The concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate. The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum. METHODS Chronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles. RESULTS Eighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90-152]min) compared to A1.25 (83 [43-108]min, p<0.001) and A1.5 (66 [18-102]min, p<0.001). During the treatment week, predialysis T50 increased significantly from the first to the third session with C1.5 (271 [234-291] to 280 [262-339]min, p = 0.002) and with A1.25 (274 [213-308] to 307 [256-337]min, p<0.001), but not with A1.5 (284 [235-346] to 300 [247-335]min, p = 0.33). CONCLUSION Calcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.
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Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications.
Grossman, C, Levin, M, Koren-Morag, N, Bornstein, G, Leibowitz, A, Ben-Zvi, I, Shemesh, J, Grossman, E
American journal of hypertension. 2018;(3):313-320
Abstract
BACKGROUND Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC. METHODS We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event. RESULTS Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50-4.21) in those without CAC and 4.4 (95% CI, 2.02-9.56) in those with CAC. CONCLUSIONS LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC.
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First-time-in-human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification.
Perelló, J, Joubert, PH, Ferrer, MD, Canals, AZ, Sinha, S, Salcedo, C
British journal of clinical pharmacology. 2018;(12):2867-2876
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AIMS: SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS This is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation. RESULTS Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 ± 21.0%, P < 0.001, 95% CI, -32.4 to 49.7). CONCLUSION The results from this study showed acceptable safety and tolerability, and lack of significant dialysability of IV SNF472. It is a potential novel treatment for cardiovascular calcification in end-stage renal disease and calciphylaxis warranting further human studies.
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Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial.
Andrews, ES, Perrenoud, L, Nowak, KL, You, Z, Pasch, A, Chonchol, M, Kendrick, J, Jalal, D
PloS one. 2018;(10):e0205831
Abstract
BACKGROUND Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. METHODS This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. FINDINGS Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. CONCLUSION These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.
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Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone.
Budoff, MJ, Ellenberg, SS, Lewis, CE, Mohler, ER, Wenger, NK, Bhasin, S, Barrett-Connor, E, Swerdloff, RS, Stephens-Shields, A, Cauley, JA, et al
JAMA. 2017;(7):708-716
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IMPORTANCE Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. CONCLUSIONS AND RELEVANCE Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00799617.
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Virtual Monochromatic Imaging in Patients with Intermediate to High Likelihood of Coronary Artery Disease: Impact of Coronary Calcification.
Carrascosa, P, Leipsic, JA, Deviggiano, A, Capunay, C, Vallejos, J, Goldsmit, A, De Zan, MC, Rodriguez-Granillo, GA
Academic radiology. 2016;(12):1490-1497
Abstract
RATIONALE AND OBJECTIVES We sought to explore the image quality and diagnostic performance of virtual monochromatic imaging derived from dual-energy computed tomography coronary angiography (DE-CTCA) in patients with intermediate to high likelihood of coronary artery disease (CAD) and the influence of calcification. MATERIALS AND METHODS Consecutive symptomatic patients with suspected CAD referred for invasive coronary angiography who underwent DE-CTCA and a coronary artery calcium scoring before the invasive procedure comprised the study population. RESULTS Sixty-seven patients were included. Image quality was significantly lower at 45 keV reconstructions (mean Likert score 45 keV 3.57 ± 0.6, 65 keV 4.07 ± 0.5, and 85 keV 4.09 ± 0.6; P < .0001). Patients with moderate calcification showed a trend toward a significant improvement in the diagnostic performance with 65 keV vs 45 keV reconstructions (45 keV, area under the curve 0.92 [95% confidence interval 0.89-0.95] vs 65 keV, area under the curve 0.96 [95% confidence interval 0.93-0.98], P = .06). The diagnostic performance of DE-CTCA was significantly lower in segments with higher coronary artery calcium scoring compared to segments with none or mild calcification, independent of the energy level applied. CONCLUSIONS In patients with intermediate to high likelihood of CAD, DE-CTCA had a good diagnostic performance, although significantly lower in segments with severe calcification.
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Prospective evaluation of the influence of iterative reconstruction on the reproducibility of coronary calcium quantification in reduced radiation dose 320 detector row CT.
Choi, AD, Leifer, ES, Yu, J, Shanbhag, SM, Bronson, K, Arai, AE, Chen, MY
Journal of cardiovascular computed tomography. 2016;(5):359-63
Abstract
BACKGROUND Coronary artery calcium (CAC) predicts coronary heart disease events and is important for individualized cardiac risk assessment. This report assesses the interscan variability of CT for coronary calcium quantification using image acquisition with standard and reduced radiation dose protocols and whether the use of reduced radiation dose acquisition with iterative reconstruction (IR; "reduced-dose/IR ") allows for similar image quality and reproducibility when compared to standard radiation dose acquisition with filtered back projection (FBP; "standard-dose/FBP") on 320-detector row computed tomography (320-CT). METHODS 200 consecutive patients (60 ± 9 years, 59% male) prospectively underwent two standard- and two reduced-dose acquisitions (800 total scans, 1600 reconstructions) using 320 slice CT and 120 kV tube voltage. Automated tube current modulation was used and for reduced-dose scans, prescribed tube current was lowered by 70%. Image noise and Agatston scores were determined and compared. RESULTS Regarding stratification by Agatston score categories (0, 1-10, 11-100, 101-400, >400), reduced-dose/IR versus standard-dose/FBP had excellent agreement at 89% (95% CI: 86-92%) with kappa 0.86 (95% CI: 0.81-0.90). Standard-dose/FBP rescan agreement was 93% (95% CI: 89-96%) with kappa = 0.91 (95% CI: 0.86-0.95) while reduced-dose/IR rescan agreement was similar at 91% (95% CI: 87-94%) with kappa 0.88 (95% CI: 0.83-0.93). Image noise was significantly higher but clinically acceptable for reduced-dose/IR (18 Hounsfield Unit [HU] mean) compared to standard-dose/FBP (16 HU; p < 0.0001). Median radiation exposure was 74% lower for reduced- (0.37 mSv) versus standard-dose (1.4 mSv) acquisitions. CONCLUSION Rescan agreement was excellent for reduced-dose image acquisition with iterative reconstruction and standard-dose acquisition with filtered back projection for the quantification of coronary calcium by CT. These methods make it possible to reduce radiation exposure by 74%. CLINICAL TRIAL REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT01621594. UNIQUE IDENTIFIER NCT01621594.
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Incremental diagnostic accuracy of computed tomography myocardial perfusion imaging over coronary angiography stratified by pre-test probability of coronary artery disease and severity of coronary artery calcification: The CORE320 study.
Sharma, RK, Arbab-Zadeh, A, Kishi, S, Chen, MY, Magalhães, TA, George, RT, Dewey, M, Rybicki, FJ, Kofoed, KF, de Roos, A, et al
International journal of cardiology. 2015;:570-7
Abstract
BACKGROUND Myocardial CT perfusion (CTP) has been validated as an incremental diagnostic predictor over coronary computed tomography angiography (CTA) in assessing hemodynamically significant stenosis. OBJECTIVES To assess the diagnostic performance of CTA and CTP alone versus combined CTA-CTP stratified by Morise's pre-test probability and coronary artery calcium (CAC, Agatston) score. METHODS 381 individuals (153 low/intermediate-risk for CAD, 83 high-risk, 145 known CAD) were further stratified based on CAC score cut-offs of 1-399 and ≥400. Area under the curve for receiver operating characteristics (AUC) was calculated to assess the diagnostic performance. Reference standards were QCA≥50% stenosis+corresponding SPECT summed stress score ≥1. RESULTS In both pre-test risk groups with an Agatston score of 1-399, AUCs of CTA-CTP were not significantly different than that from CTA alone. In the low/intermediate-risk group with CAC score 1-399, AUC for CTA-CTP (89) was higher than that for CTP (76, p=0.003) alone. In the same group with CAC score ≥400, AUCs were higher for CTA-CTP (97) than that for CTA (88, p=0.030) and CTP (83, p=0.033). In high risk/known CAD patients with CAC 1-399, diagnostic performance for CTA-CTP (77) was superior to CTP (71, p=0.037) alone. In the high risk/known CAD group with CAC score ≥400, AUCs for combined imaging were higher (86) than that for CTA (75, p<0.001) as well as CTP (78, p=0.020). CONCLUSIONS The incremental diagnostic accuracy of CTP over CTA persists in patients across severity spectra of pre-test probability of CAD and coronary artery calcification. In patients with severe coronary calcification (CAC score≥400), combined CTA-CTP has better diagnostic accuracy than CTA and CTP alone.