To fully characterize beam-hardening effects caused by iodinated contrast medium in the left ventricular (LV) cavity and aorta in the assessment of myocardial perfusion at computed tomography (CT) ...and to validate a beam-hardening artifact correction algorithm that considers fluid-filled vessels and chambers important sources of beam hardening.
The Johns Hopkins University animal care and use committee approved all procedures. An anatomically correct LV and myocardial phantom to characterize beam-hardening artifacts was designed. Following validation in the phantom, the beam-hardening correction (BHC) algorithm was applied to 256-detector row dynamic volume CT images in a canine ischemia model (n = 5) during adenosine stress, and the effect of beam hardening was determined by comparing regional dynamic volume CT perfusion metrics (myocardial upslope normalized by maximum LV blood pool attenuation) with microsphere-derived myocardial blood flow (MBF). A paired Student t test was used to compare continuous variables from the same subject but under different conditions, while linear regression analysis was performed to estimate the slope and statistical significance of the relationship between CT-derived perfusion metrics and microsphere-derived MBF.
Beam-hardening artifacts were successfully reproduced in phantom studies and were eliminated with the BHC algorithm. The correlation coefficient of CT-derived perfusion metrics and microsphere-derived MBF improved from 0.60 to 0.74 (P > .05) following correction in the animal model.
Beam-hardening artifacts confound dynamic volume CT assessment of myocardial perfusion. Application of the BHC algorithm is helpful for improving accuracy of myocardial perfusion at dynamic volume CT.
Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance Heralds an Adverse Prognosis in Nonischemic Cardiomyopathy Katherine C. Wu, Robert G. Weiss, David R. Thiemann, Kakuya Kitagawa, André ...Schmidt, Darshan Dalal, Shenghan Lai, David A. Bluemke, Gary Gerstenblith, Eduardo Marbán, Gordon F. Tomaselli, João A. C. Lima Predicting prognosis in nonischemic cardiomyopathy patients is challenging, and current risk stratification approaches are limited. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis, which appears as late gadolinium enhancement (LGE). The presence of LGE predicts an 8-fold increased risk of an adverse cardiac outcome (hazard ratio 8.2, 95% confidence interval 2.2 to 30.9; p = 0.002), after controlling for baseline variables. A CMR LGE may reflect the transition from compensated to decompensated state resulting from long-term stressors such as sustained adrenergic activation and/or the mechanical disadvantages caused by left ventricular remodeling leading to increasing fibrosis. Identifying CMR LGE may significantly improve risk stratification strategies in this high-risk population.
Objectives This study was designed to evaluate whether the absence of coronary calcium could rule out ≥50% coronary stenosis or the need for revascularization. Background The latest American Heart ...Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients. Methods A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before. Results In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 ± 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of ≥50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 ≥50% stenosis. The overall sensitivity for CS = 0 to predict the absence of ≥50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with ≥50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium. Conclusions The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification. (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors CORE-64; NCT00738218 )
Left ventricular (LV) trabeculation is highly variable among individuals and is increased in some diseases (e.g., congenital heart disease or cardiomyopathies), but its significance in ...population-representative individuals is unknown.
The goal of this study was to determine if excessive LV trabeculation in population-representative individuals is associated with preceding changes in cardiac volumes and function.
For technical reasons, the extent of trabeculation, which is expressed as the ratio of noncompacted to compacted (NC/C) myocardium, was measured on cardiac magnetic resonance (CMR) long-axis cine images in 2,742 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (mean age 68.7 years; 52.3% women; 56.4% with hypertension; 16.8% with diabetes) at examination 5. These were considered in quintiles of trabeculation extent; the NC/C ratio of quintile 5 was 2.46 to 5.41. We determined the relationship between the maximal NC/C ratio and the preceding change (9.5 years between examinations 1 and 5) in end-systolic volume indexed (ESVi) to body surface area. Secondary analyses assessed the associations between the maximal NC/C ratio and preceding changes in end-diastolic volume indexed (EDVi) to body surface area and the ejection fraction (EF).
Over 9.5 years, the ESVi decreased by 1.3 ml/m(2), the EDVi decreased by 5.1 ml/m(2), and the EF decreased by 0.6% (p < 0.0001). Even in subjects with excessive trabeculation, there were no clinically relevant differences in LV volumes and systolic function changes among the quintiles of trabeculation extent.
Greater extent of, and even excessive, LV trabeculation measured in end-diastole in asymptomatic population-representative individuals appeared benign and was not associated with deterioration in LV volumes or function during an almost 10-year period.
The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic ...population-based cohort.
The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese ( ≥ 30 kg/m(2)).
The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters.
Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects.
To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of ...obstructive coronary artery disease (CAD).
Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years interquartile range, 53-67 years) with clinical suspicion of CAD from the CORE-64 multicenter study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (≥ 50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (< 90°), moderate (90°-180°), or severe (> 180°) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses.
A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05).
In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.
The purpose of this study was to evaluate the relationship of left ventricular (LV) mass and geometry measured with cardiac magnetic resonance imaging (MRI) to incident cardiovascular events in the ...MESA (Multi-Ethnic Study of Atherosclerosis) study.
MRI is highly accurate for evaluation of heart size and structure and has not previously been used in a large epidemiologic study to predict cardiovascular events.
A total of 5,098 participants in the MESA study underwent cardiac MRI at the baseline examination and were followed up for a median of 4 years. Cox proportional hazard models were constructed to predict the end points of coronary heart disease (CHD), stroke, and heart failure (HF) after adjustment for cardiovascular risk factors.
A total of 216 incident events were observed during the follow-up period. In adjusted models, the end points of incident CHD and stroke were positively associated with increased LV mass-to-volume ratio (CHD, hazard ratio HR: 2.1 per g/ml, p = 0.02; stroke, HR: 4.2 per g/ml, p = 0.005). In contrast, LV mass showed the strongest association with incident HF events (HR: 1.4 per 10% increment, p < 0.0001). The HF events occurred primarily in participants with LV hypertrophy, that is, >or=95th percentile of LV mass (HR: 8.6, 95% confidence interval: 3.7 to 19.9, reference group <50th percentile of LV mass).
The LV size was related to incident HF, stroke, and CHD in this multiethnic cohort. Whereas body size-adjusted LV mass alone predicted incident HF, concentric ventricular remodeling predicted incident stroke and CHD.
This study sought to determine the relationship of cardiovascular magnetic resonance (CMR) measures of tissue composition to age in the Multi-Ethnic Study of Atherosclerosis (MESA).
Animal and human ...studies have demonstrated increased collagen deposition in senescent hearts. New CMR indices of tissue composition by using T1 mapping are sensitive to the presence of myocardial fibrosis.
A total of 1,231 study participants (51% women; age range 54 to 93 years) of the MESA cohort were evaluated with T1 mapping by using 1.5-T CMR scanners. None of the participants had focal scar on delayed enhancement CMR. Single-slice T1 mapping was performed at the midventricular level before and at 12- and 25-min delay after administration of gadolinium contrast by using a modified Look-Locker inversion recovery sequence. The partition coefficient was determined by the slope of the linear relationship of (1/T1myo vs. 1/T1blood). The extracellular volume fraction (ECV) was derived accounting for the hematocrit level. Multivariable regression analyses were performed, adjusting for traditional risk factors and left ventricular structure.
Women had significantly greater partition coefficient, ECV, and precontrast T1 than men, as well as lower post-contrast T1 values (all p < 0.05). In general, linear regression analyses demonstrated that greater partition coefficient, pre-contrast T1 values, and ECV were associated with older age in men (multivariate regression coefficients = 0.01; 5.9 ms; and 1.04% per 10 years' change; all p < 0.05). ECV was also significantly associated with age in women after multivariable adjustments.
CMR parameters that have been associated with myocardial fibrosis were related to older age in the MESA study. Women had higher ECV than men but less ECV change over time.
Abstract
Aims
Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute ...myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial.
Methods and results
We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients.
Conclusion
Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs.
Trial registration
Clinicaltrials.gov identifier: NCT01458405.
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