Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent ß-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.

Risk factors based vessel-specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry.

BACKGROUND AND HYPOTHESIS: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. METHODS: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. RESULTS: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. CONCLUSIONS: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.

The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study.

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy.

BACKGROUND: The aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). METHODS: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. RESULTS: Of 944 (62 ±â€¯9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ±â€¯221mm3 versus 72.9 ±â€¯84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ±â€¯31.4mm3/yr versus 14.9 ±â€¯20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ±â€¯24mm3/yr versus 7 ±â€¯11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. CONCLUSION: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

Pitfalls and feasibility of a protocol of virtual colonography designed for the screening of colo-rectal pre-cancerous lesions.

PURPOSE: To evaluate the pitfalls occurring during the virtual colonoscopy examination performed with a protocol designed for screening purposes. MATERIALS AND METHODS: 40 patients underwent a spiral CT for virtual colonoscopic evaluation with the following parameters: collimation 3 mm, feed 6 mm.rot(-1), pitch 2 and increment 1 mm in supine position. Virtual colonography examination was carried out using a dedicated workstation equipped with a software which allows to generate 3D images and virtual endoscopic views. Colon distension, fluid and fecal material were assessed on a 3 point scale. RESULTS: Distension score was 0.50. Left colon and cecum score was 0.32 while in the sigmoid and rectum the score was worse with 0.86. Fluid and fecal residues scores were 0.31 and 0.19 respectively. On almost half of the patients additional scans would be necessary. The main cause of additional scans is suboptimal intestinal preparation and colon distension. CONCLUSION: The use of virtual colonoscopy for screening purposes will be possible through the further technical development and with the optimisation of the protocols, particularly by the improvement of colon cleansing and distension.

Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography.

Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/infinity, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35+/-10, 91+/-7, 246+/-18, 511+/-89 HU) and plaque (22+/-22, 50+/-26, 107+/-36, 152+/-67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT.

CT and MR colonography: scanning techniques, postprocessing, and emphasis on polyp detection.

In the last decade, computed tomographic (CT) and magnetic resonance (MR) colonography, two new cross-sectional techniques for imaging of the colon, emerged. Both techniques show promising initial results in the detection of polyps equal to or greater than 1 cm in diameter in symptomatic patients. Imaging protocols are still mostly under development and prone to change. Both CT and MR colonography generate a large number of source images, which have to be read carefully for filling defects and, if intravenous contrast material is used, enhancing lesions. An important postprocessing technique is multiplanar reformatting, which allows the viewer to see potential lesions in an orientation other than that of the source images. Virtual endoscopy, a volume rendering technique that generates images from within the colon lumen, is used for problem solving. CT and MR colonography have potential advantages over colonoscopy and double-contrast barium enema examination: multiplanar capabilities, detection of enhancing lesions that make the distinction between fecal residue and true lesion possible, and ante- and retrograde virtual colonoscopy. Currently, a number of studies suggest that patients have a preference for CT colonography over colonoscopy. Patients consider bowel cleansing the most uncomfortable part of any colon examination; hence, from the acceptance point of view, fecal tagging techniques are promising. Before CT and MR colonography can be implemented in daily practice, they must show approximately the same accuracy as colonoscopy for polyp detection in both symptomatic and screening patients.