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1.
The predictive value of coronary artery calcium detected by computed tomography in a prospective study on cardiac allograft vasculopathy in heart transplant patients.
Günther, A, Andersen, R, Gude, E, Jakobsen, J, Edvardsen, T, Sandvik, L, Abildgaard, A, Aaberge, L, Gullestad, L
Transplant international : official journal of the European Society for Organ Transplantation. 2018;(1):82-91
Abstract
The predictive value of coronary artery calcium (CAC) in heart transplant (HTX) patients is not established. We explored if the absence of CAC on computed tomography (CT) could exclude moderate and severe cardiac allograft vasculopathy [CAV2-3 ; the International Society for Heart and Lung Transplantation (ISHLT) recommended nomenclature] and significant coronary artery stenosis (diameter reduction ≥50%) and predict long-term clinical outcomes. HTX recipients (n = 133) were prospectively included and underwent CT for CAC scoring and invasive coronary angiography (ICA) 7.8 ± 5.0 years after HTX. CAC was detected in 73 (55%) patients. The absence of CAC on CT had a negative predictive value of 97% for ISHLT CAV2-3 and 88% for significant stenosis on ICA. During 7.5 ± 2.6 years of follow-up after CAC CT (n = 127), there were 57 (45%) nonfatal major adverse cardiac events and 23 (18%) deaths or graft losses registered as first events. Patients with CAC had significantly more events (P = 0.011). In an adjusted Cox regression analysis, the presence of CAC was significantly associated with a negative outcome (HR 1.8, 95% CI 1.1-3.0; P = 0.023). The absence of CAC predicted low prevalences of ISHLT CAV2-3 and significant coronary artery stenosis in HTX patients. The presence of CACS was significantly associated with a worse long-term outcome.
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Coronary risk assessment using traditional risk factors with CT coronary artery calcium scoring in clinical practice.
Kerut, EK, Hall, ME, Turner, MC, McMullan, MR
Echocardiography (Mount Kisco, N.Y.). 2018;(8):1216-1222
Abstract
As coronary artery calcium (CAC) is atherosclerosis and not just a marker of cardiovascular (CV) disease, measurement of a patient's coronary artery calcium score (CACS) is a strong predictor of risk. Clinically performed in asymptomatic patients, the CACS, along with several CV risk factors, namely age, sex, ethnicity, diabetes, tobacco use, family history, cholesterol level, blood pressure, and use of cholesterol or hypertensive medications, provide a predictive model of 10 year risk for CV events. A smartphone "App" makes this quick to obtain and use. This helps the clinician in making recommendations for both lifestyle changes and statin therapy. Those patients in which the most benefit occur from measurement of a CACS are those at an intermediate CV risk. Measurement of the CACS has become an integral part of the clinician's assessment of a patient's CV risk and for guiding preventative therapies.
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Coronary Artery Calcium Imaging in the ROBINSCA Trial: Rationale, Design, and Technical Background.
Vonder, M, van der Aalst, CM, Vliegenthart, R, van Ooijen, PMA, Kuijpers, D, Gratama, JW, de Koning, HJ, Oudkerk, M
Academic radiology. 2018;(1):118-128
Abstract
RATIONALE AND OBJECTIVES To describe the rationale, design, and technical background of coronary artery calcium (CAC) imaging in the large-scale population-based cardiovascular disease screening trial (Risk Or Benefit IN Screening for CArdiovascular Diseases [ROBINSCA]). MATERIALS AND METHODS First, literature search was performed to review the logistics, setup, and settings of previously performed CAC imaging studies, and current clinical CAC imaging protocols of participating centers in the ROBINSCA trial were evaluated. A second literature search was performed to evaluate the impact of computed tomography parameter settings on CAC score. RESULTS Based on literature reviews and experts opinion an imaging protocol accompanied by data management protocol was created for ROBINSCA. The imaging protocol should consist of a fixed tube voltage, individually tailored tube current setting, mid-diastolic electrocardiography-triggering, fixed field-of-view, fixed reconstruction kernel, fixed slice thickness, overlapping reconstruction and without iterative reconstruction. The analysis of scans is performed with one type and version of CAC scoring software, by two dedicated and experienced researchers. The data management protocol describes the organization of data handling between the coordinating center, participating centers, and core analysis center. CONCLUSION In this paper we describe the rationale and technical considerations to be taken in developing CAC imaging protocol, and we present a detailed protocol that can be implemented for CAC screening purposes.
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Coronary calcium score improves the estimation for pretest probability of obstructive coronary artery disease and avoids unnecessary testing in individuals at low extreme of traditional risk factor burden: validation and comparison of CONFIRM score and genders extended model.
Wang, M, Liu, Y, Zhou, X, Zhou, J, Zhang, H, Zhang, Y
BMC cardiovascular disorders. 2018;(1):176
Abstract
BACKGROUND Reliability of models for estimating pretest probability (PTP) of obstructive coronary artery disease (CAD) has not been investigated in individuals at low extreme of traditional risk factor (RF) burden. Thus, we sought to validate and compare CONFIRM score and Genders extended model (GEM) among these individuals. METHODS We identified symptomatic individuals with 0 or 1 RF who underwent coronary calcium scan and coronary computed tomographic angiography (CCTA). Follow-up clinical data were also recorded. PTP of obstructive CAD for every individual was estimated according to CONFIRM score and GEM, respectively. Area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and Hosmer-Lemeshow (H-L) test were used to assess the performance of models. RESULTS There were 1201 individuals with 0 RF and 2415 with 1 RF. The AUC for GEM was significantly larger than that for CONFIRM score, no matter in individuals with 0 (0.843 v.s. 0.762, p < 0.0001) or 1 (0.823 v.s. 0.752, p < 0.0001) RF. Compared to CONFIRM score, GEM demonstrated positive IDI (5% in individuals with 0 RF and 8% in individuals with 1 RF), positive NRI (41.50% in individuals with 0 RF and 40.19% in individuals with 1 RF), better prediction of clinical events and less discrepancy between observed and predicted probabilities, resulting in a significant decrease of unnecessary testing, especially in negative individuals. CONCLUSION In individuals at low extreme of traditional RF burden of CAD, the addition of coronary calcium score provided a more accurate estimation for PTP and application of GEM instead of CONFIRM score could avoid unnecessary testing.
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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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Machine learning in cardiac CT: Basic concepts and contemporary data.
Singh, G, Al'Aref, SJ, Van Assen, M, Kim, TS, van Rosendael, A, Kolli, KK, Dwivedi, A, Maliakal, G, Pandey, M, Wang, J, et al
Journal of cardiovascular computed tomography. 2018;(3):192-201
Abstract
Propelled by the synergy of the groundbreaking advancements in the ability to analyze high-dimensional datasets and the increasing availability of imaging and clinical data, machine learning (ML) is poised to transform the practice of cardiovascular medicine. Owing to the growing body of literature validating both the diagnostic performance as well as the prognostic implications of anatomic and physiologic findings, coronary computed tomography angiography (CCTA) is now a well-established non-invasive modality for the assessment of cardiovascular disease. ML has been increasingly utilized to optimize performance as well as extract data from CCTA as well as non-contrast enhanced cardiac CT scans. The purpose of this review is to describe the contemporary state of ML based algorithms applied to cardiac CT, as well as to provide clinicians with an understanding of its benefits and associated limitations.
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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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Abstract
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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Role of pyrophosphate in vascular calcification in chronic kidney disease.
Azpiazu, D, Gonzalo, S, González-Parra, E, Egido, J, Villa-Bellosta, R
Nefrologia. 2018;(3):250-257
Abstract
Vascular calcification is a pathology characterized by the deposition of calcium-phosphate in cardiovascular structures, mainly in the form of hydroxyapatite crystals, resulting in ectopic calcification. It is correlated with increased risk of cardiovascular disease and myocardial infarction in diabetic patients and in those with chronic kidney disease (CKD). Vascular smooth muscle cells are sensitive to changes in inorganic phosphate (Pi) levels. They are able to adapt and modify some of their functions and promote changes which trigger calcification. Pi is regulated by parathyroid hormone and 1,25-dihydroxyvitamin D. Changes in the transport of Pi are the primary factor responsible for the regulation of Pi homeostasis and the calcification process. Synthesis of calcification inhibitors is the main mechanism by which cells are able to prevent vascular calcification. Extracellular pyrophosphate (PPi) is a potent endogenous inhibitor of calcium-phosphate deposition both in vivo and in vitro. Patients with CKD show lower levels of PPi and increased activity of the enzyme alkaline phosphatase. Numerous enzymes implicated in the metabolism of PPi have been associated with vascular calcifications. PPi is synthesized from extracellular ATP by nucleotide pyrophosphatase/phosphodiesterase from extracellular ATP hydrolysis. PPi is hydrolyzed into Pi by tissue-nonspecific alkaline phosphatase. ATP can be hydrolyzed to Pi via the ectonucleoside triphosphate diphosphohydrolase family. All these enzymes must be in balance, thereby preventing calcifications. However, diseases like CKD or diabetes induce alterations in their levels. Administration of PPi could open up new treatment options for these patients.
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Effect of Intensive and Standard Pitavastatin Treatment With or Without Eicosapentaenoic Acid on Progression of Coronary Artery Calcification Over 12 Months - Prospective Multicenter Study.
Miyoshi, T, Kohno, K, Asonuma, H, Sakuragi, S, Nakahama, M, Kawai, Y, Uesugi, T, Oka, T, Munemasa, M, Takahashi, N, et al
Circulation journal : official journal of the Japanese Circulation Society. 2018;(2):532-540
Abstract
BACKGROUND The effect of lipid-lowering agents on progression of coronary artery calcification (CAC) remains unclear. We evaluated the effects of pitavastatin 2 mg/day (PIT2), pitavastatin 4 mg/day (PIT4), and PIT2 combined with eicosapentaenoic acid (PIT2+EPA) on CAC progression.Methods and Results:This prospective multicenter study in Japan included patients with an Agatston score of 1-999, hypercholesterolemia, and no evidence of cardiovascular disease. Patients were allocated into PIT2, PIT4, or PIT2+EPA groups. The primary outcome was the annual percent change in Agatston score in all patients. In total, 156 patients who had multi-detector row computed tomography without any artifacts were included in the primary analysis. Pitavastatin did not significantly reduce the annual progression rate of the Agatston score (40%; 95% CI: 19-61%). The annual progression rate of Agatston score in the PIT2 group was not significantly different from that in the PIT4 group (34% vs. 42%, respectively; P=0.88) or the PIT2+EPA group (34% vs. 44%, respectively; P=0.80). On post-hoc analysis the baseline ratio of low- to high-density lipoprotein cholesterol was a significant predictor of non-progression of Agatston score by pitavastatin (OR, 2.17; 95% CI: 1.10-44.12; P=0.02). CONCLUSIONS Pitavastatin does not attenuate progression of CAC. Intensive pitavastatin treatment and standard treatment with EPA does not reduce progression of CAC compared with standard treatment.
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[Calcific uremic arteriolopathy in hemodialysis patient, review of literature through five cases reports].
Chettati, M, Adnouni, A, Fadili, W, Laouad, I
Nephrologie & therapeutique. 2018;(6):439-445
Abstract
Calcific uremic arteriolopathy, also called calciphylaxis, is a rare and severe disorder that presents with skin ischemia and necrosis, sometimes it presents with systemic necrosis, the process is secondary to the obliteration of the arterioles first by sub-intimal calcium deposits and then by thrombosis. These lesions can often lead to death due to infectious complications and comorbidities such as diabetes, obesity, arteritis, diffuse vascular calcifications, heart disease and undernutrition. The diagnosis is suggested by the characteristic ischemic skin lesions and their distribution, often bilateral and painful, associeted with calcific uremic arteriolopathy risk factors (phosphocalcic abnormalities, anti-vitamin K). The presence of radiological vascular calcifications is highly suggesting the diagnosis, but remains not very specific. The indication of skin biopsy is rare and reserved for difficult diagnoses. The goals of treatment are: reduce the extension of calcification and treatment of mineral and bone metabolism disorders of end-stage renal disease, dialysis adequacy, local treatment of skin lesions, tissue oxygenation, pain management, discontinuation and contraindication of medications that may contribute to the disorder. We propose to discuss it from a review of the literature and illustrate it with five clinical cases.