Hypoxia But Not Inflammation Augments Glucose Uptake in Human Macrophages Implications For Imaging Atherosclerosis With (18)Fluorine-Labeled 2-Deoxy-D-Glucose Positron Emission Tomography

OBJECTIVES: Patient studies suggest that positron emission tomography (PET) using  (18)fluorine-labeled 2-deoxy-D-glucose FdG can detect “active” atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the FdG uptake signals observed clinically.

METHODS: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake.

RESULTS: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques-regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines.

CONCLUSIONS: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal.

PMID: 21798423

Relationship Between Location and Size of Myocardial Infarction and their Reciprocal Influences on Post-Infarction Left Ventricular Remodelling

OBJECTIVES: To assess the intricate relationship between myocardial infarction (MI) location and size and their reciprocal influences on post-infarction left ventricular (LV) remodelling.

METHODS: A cohort of 260 reperfused ST-segment elevation MI patients was prospectively studied with cardiovascular magnetic resonance at 1 week (baseline) and 4 months (follow-up). Area at risk (AAR) and MI size were quantified by T2-weighted and late-gadolinium enhancement imaging, respectively. Adverse LV remodelling was defined as an increase in LV end-systolic volume ≥15% at follow-up.

RESULTS: One hundred and twenty-seven (49%) patients had anterior MI and 133 (51%) patients had non-anterior MI. Although the degree of myocardial salvage was similar between groups (P = 0.74), anterior MI patients had larger AAR and MI size than non-anterior MI patients yielding worse regional and global LV function at baseline and follow-up. At univariable analysis, anterior MI was associated with increased risk of adverse LV remodelling (P = 0.017) and lower LV ejection fraction (EF) at follow-up (P = 0.001), but not when accounted for baseline MI size. Accordingly, at multivariable analysis, baseline MI size but not its location was an independent predictor of adverse LV remodelling (odds ratio = 1.061, P < 0.001) and EF at follow-up (β-coefficient = −0.255, P < 0.001).

CONCLUSIONS: Anterior MI patients experience more pronounced post-infarction LV remodelling and dysfunction than non-anterior MI patients due to a greater magnitude of irreversible ischaemic LV damage without any independent contribution of MI location.

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Diagnostic Accuracy of Dual-Source CT Coronary Angiography With Prospective ECG-Triggering on Different Heart Rate Patients

OBJECTIVES: To evaluate the diagnostic accuracy of dual-source CT (DSCT) prospective ECG-triggering coronary angiography in patients with different heart rate (HR).

METHODS: 103 patients with suspected coronary artery disease underwent DSCT prospective ECG-triggered coronary angiography and invasive coronary angiography (ICA). The patients were grouped by HR during CT scans: low HR (≤60 bpm, n = 34); medium HR (60 < HR ≤ 70 bpm, n = 36) and high HR (>70 bpm, n = 33). The sensitivity and specificity of DSCT in detecting ≥50% stenosis were compared among subgroups where ICA was the gold standard. Image quality was scored using a 4-point scale.

RESULTS: A total of 1,580 (95.9%) coronary artery segments were evaluable. Sensitivity and specificity were 82.8% and 98.4%, 88.3% and 98.7%, and 80.3% and 98.6% for different subgroups (all p > 0.05). The overall area under the curve of the receiver-operating characteristic analysis was 0.94. The image quality scores were 3.1 ± 0.3, 3.1 ± 0.3 and 3.0 ± 0.4 for subgroups (p > 0.05). The overall average effective radiation dose was 3.60 ± 1.60 mSv.

CONCLUSIONS: DSCT coronary angiography with prospective ECG-triggering could be just as accurate in patients with medium to high HR compared to those with low HR.

PMID: 21484353

Mitral Valve Abnormalities Identified by Cardiovascular Magnetic Resonance Represent a Primary Phenotypic Expression of Hypertrophic Cardiomyopathy

OBJECTIVES: Whether morphological abnormalities of the mitral valve represent part of the hypertrophic cardiomyopathy (HCM) disease process is unresolved. Therefore, we applied cardiovascular magnetic resonance to characterize mitral valve morphology in a large HCM cohort.

METHODS: Cine cardiac magnetic resonance images were obtained in 172 HCM patients (age, 42±18 years; 62% men) and 172 control subjects. In addition, 15 HCM gene-positive/phenotype-negative relatives were studied.

RESULTS: Anterior mitral leaflet (AML) and posterior mitral leaflet lengths were greater in HCM patients than in control subjects (26±5 versus 19±5 mm, P2 SDs above controls). Leaflet length was increased compared with controls in virtually all HCM age groups, including young patients 15 to 20 years of age (AML, 26±5 versus 21±4 mm; P=0.0002) and those ≥60 years of age (AML, 26±4 versus 19±2 mm; P2.0 was associated with subaortic obstruction (P=0.001). In addition, AML length in 15 genotype-positive relatives without LV hypertrophy exceeded that of matched control subjects (21±3 versus 18±3 mm; P

CONCLUSIONS: In HCM, mitral valve leaflets are elongated independently of other disease variables, likely constituting a primary phenotypic expression of this heterogeneous disease, and are an important morphological abnormality responsible for LV outflow obstruction in combination with small outflow tract dimension. These findings suggest a novel role for cardiac magnetic resonance in the assessment of HCM.

PMID: 21670234

Less Common Causes of Disease Involving the Coronary Arteries: MDCT Findings

OBJECTIVES: We aimed to illustrate and describe various imaging findings of nonatherosclerotic, nonanomalous coronary artery diseases (CADs) revealed by cardiac MDCT.

CONCLUSIONS: Cardiac MDCT can show various causes of nonatherosclerotic CADs and of coronary atherosclerosis. Radiologists should be aware of the diverse imaging findings of nonatherosclerotic, nonanomalous CADs that can be identified with cardiac MDCT to facilitate accurate diagnosis and proper management.

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Cardiac Resynchronisation Therapy Guided by Late Gadolinium-Enhancement Cardiovascular Magnetic Resonance

OBJECTIVES: Myocardial scarring at the LV pacing site leads to incomplete resynchronization and a suboptimal symptomatic response to CRT. We sought to determine whether the use of late gadolinium cardiovascular magnetic resonance (LGE-CMR) to guide left ventricular (LV) lead deployment influences the long-term outcome of cardiac resynchronization therapy (CRT).

METHODS: 559 patients with heart failure (age 70.4 +/- 10.7 yrs [mean +/- SD]) due to ischemic or non-ischemic cardiomyopathy underwent CRT. Implantations were either guided (+CMR) or not guided (-CMR) by LGE-CMR prior to implantation. Fluoroscopy and LGE-CMR were used to localize the LV lead tip and and myocardial scarring retrospectively. Clinical events were assessed in three groups: +CMR and pacing scar (+CMR+S); CMR and not pacing scar (+CMR-S), and; LV pacing not guided by CMR (-CMR).

RESULTS: Over a maximum follow-up of 9.1 yrs, +CMR+S had the highest risk of cardiovascular death (HR: 6.34), cardiovascular death or hospitalizations for heart failure (HR: 5.57) and death from any cause or hospitalizations for major adverse cardiovascular events (HR: 4.74) (all P < 0.0001), compared with +CMR-S. An intermediate risk of meeting these endpoints was observed for -CMR, with HRs of 1.51 (P = 0.0726), 1.61 (P = 0.0169) and 1.87 (p = 0.0005), respectively. The +CMR+S group had the highest risk of death from pump failure (HR: 5.40, p<0.0001) and sudden cardiac death (HR: 4.40, p = 0.0218).

CONCLUSIONS: Compared with a conventional implantation approach, the use of LGE-CMR to guide LV lead deployment away from scarred myocardium results in a better clinical outcome after CRT. Pacing scarred myocardium was associated with the worst outcome, in terms of both pump failure and sudden cardiac death.

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Detection of Disrupted Plaques by Coronary CT: Comparison With Angioscopy

OBJECTIVES: Disrupted plaques are the major cause of acute coronary syndrome (ACS). Although the detection of vulnerable plaques by coronary CT (CCT) has been examined and reported, there has been no report on the detection of disrupted plaques by CCT. The objective was to test the ability of CCT to detect disrupted coronary plaques.

METHODS: 32 consecutive patients with suspected ischaemic heart disease who underwent successful coronary angioscopic examination and CCT were analysed. Yellow plaques of colour grade 1␣3 and disrupted yellow plaques were examined by angioscopy. CCT findings (low attenuation, positive remodelling and ring-like enhancement) were examined for each site of yellow plaques.

RESULTS: In the 32 patients, 65 yellow plaques were detected. Higher-colour-grade yellow plaques and disrupted yellow plaques had a significantly higher incidence of CCT findings: low attenuation (grade 1 vs grade 2 vs grade 3, 18% vs 59% vs 69%; non-disrupted vs disrupted, 36% vs 66%), positive remodelling (24% vs 59% vs 75%; 33% vs 75%), and ring-like enhancement (0% vs 19% vs 25%; 6% vs 44%). Positive and negative predictive values for ring-like enhancement to detect disrupted plaque were 88% and 63%, respectively; those for the combined CCT findings (low attenuation, positive remodelling and ring-like enhancement) to detect disrupted plaque were 90% and 58%, respectively.

CONCLUSIONS: CCT findings were associated with disrupted plaques confirmed by angioscopy. Ring-like enhancement had a high positive predictive value for detecting disrupted plaque.

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Clinical Implications of Midventricular Obstruction in Patients With Hypertrophic Cardiomyopathy

OBJECTIVES: We investigated the prevalence, clinical characteristics, and prognosis of hypertrophic cardiomyopathy (HCM) patients with midventricular obstruction (MVO). Previous descriptions of patients with MVO have been confined to case reports or small patient series, and this subgroup of HCM patients has therefore remained underrecognized.

METHODS: The study population included 490 HCM patients. Left ventricular MVO was diagnosed when the peak midcavitary gradient was estimated to be 30 mm Hg.

RESULTS: MVO was identified in 46 patients (9.4%). Patients with MVO were more likely to be symptomatic than those without. MVO was found to be an independent determinant of HCM-related death in multivariate models (hazard ratio [HR]: 2.23, p = 0.016), and this trend was especially pronounced for the combined endpoint of sudden death and potentially lethal arrhythmic events (HR:3.19, p < 0.001). Apical aneurysm formation was identified in 28.3% of patients with MVO and strongly predicted HCM-related death (HR: 3.47, p = 0.008) and the combined endpoint of suddendeath and potentially lethal arrhythmic events (HR: 5.08, p < 0.001). In addition, MVO without apical aneurysm was also identified as an independent determinant of the combined endpoint of sudden death and potentially lethal arrhythmic events (HR: 2.43, p = 0.045).

CONCLUSIONS: This analysis identified MVO as an independent predictor of adverse outcomes, especially the combined endpoint of sudden death and potentially lethal arrhythmic events. Our results suggest that longer periods of exposure to MVO might lead to unfavorable consequences. They also support the principle that the presence of MVO in patients with HCM has important pathophysiologicalimplications.

PMID:

Assessment of Thoracic Aortic Elasticity: A Preliminary Study Using Electrocardiographically Gated Dual-Source CT

OBJECTIVES: To gain a new insight into the elastic properties of the thoracic aorta in patients without aortic diseases using electrocardiographically (ECG)-gated dual-source (DS) CT.

METHODS: 56 subjects with no cardiovascular disease, selected from 2,700 people undergoing ECG-gated DSCT examination, were divided into three groups according to their age. CT data were reconstructed in 5% step throughout the RR interval. Diameter and area were measured at the curve of the ascending aorta (AA) and at the same level of the descending aorta (DA). The pulsation and elasticity of the aorta were evaluated.

RESULTS: Aortic diameter changes were noted throughout the cardiac cycle. The maximum average diameter was seen at an RR interval of 24.02 ± 4.99% for the AA and 25.63 ± 4.77% for the DA. The minimum was at 93.5 ± 4.04% for the AA and 96.6 ± 4.58% for the DA. There was an age-dependent decrease in elasticity, while different correlation coefficients were found between various age groups and different elastic parameters.

CONCLUSIONS: The properties of aortic pulsation and wall elasticity could be well shown by ECG-gated DSCT. The new findings regarding segment difference and age relevance were significant and should be taken into account in clinical trials and treatments for the elasticity related cardiovascular diseases.

PMID: 21327586

Prognostic Value of CT Angiography for Major Adverse Cardiac Events in Patients With Acute Chest Pain From the Emergency Department 2-Year Outcomes of the ROMICAT Trial

OBJECTIVES: The aim of this study was to determine the 2-year prognostic value of cardiac computed tomography (CT) for predicting major adverse cardiac events (MACE) in patients presenting to the emergency department (ED) with acute chest pain. CT has high potential for early triage of acute chest pain patients. However, there is a paucity of data regarding the prognostic value of CT in this ED cohort.

METHODS: We followed 368 patients from the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial (age 53 ± 12 years; 61% male) who presented to the ED with acute chest pain, negative initial troponin, and a nonischemic electrocardiogram for 2 years. Contrast-enhanced 64-slice CT was obtained during index hospitalization, and caregivers and patients remained blinded to the results. CT was assessed for the presence of plaque, stenosis (>50% luminal narrowing), and left ventricular regional wall motion abnormalities (RWMA). The primary endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization.

RESULTS: Follow-up was completed in 333 patients (90.5%) with a median follow-up period of 23 months. At the end of the follow-up period, 25 patients (6.8%) experienced 35 MACE (no cardiac deaths, 12 myocardial infarctions, and 23 revascularizations). Cumulative probability of 2-year MACE increased across CT strata for coronary artery disease (CAD) (no CAD 0%; nonobstructive CAD 4.6%; obstructive CAD 30.3%; log-rank p < 0.0001) and across combined CT strata for CAD and RWMA (no stenosis or RWMA 0.9%; 1 feature-either RWMA [15.0%] or stenosis [10.1%], both stenosis and RWMA 62.4%; log-rank p < 0.0001). The c statistic for predicting MACE was 0.61 for clinical Thrombolysis In Myocardial Infarction risk score and improved to 0.84 by adding CT CAD data and improved further to 0.91 by adding RWMA (both p < 0.0001).

CONCLUSIONS: CT coronary and functional features predict MACE and have incremental prognostic value beyond clinical risk score in ED patients with acute chest pain. The absence of CAD on CT provides a 2-year MACE-free warranty period, whereas coronary stenosis with RWMA is associated with the highest risk of MACE.

PMID: 21565735

Impact of Coronary Computed Tomographic Angiography Results on Patient and Physician Behavior in a Low-Risk Population

OBJECTIVES: The impact of screening coronary computed tomographic angiography (CCTA) on physician and patient behavior is unclear.

METHODS: We studied asymptomatic patients from a health-screening program. Our study population comprised 1000 patients who underwent CCTA as part of a prior study and a matched control group of 1000 patients who did not. We assessed medication use, secondary test referrals, revascularizations, and cardiovascular events at 90 days and 18 months.

RESULTS: A total of 215 patients in the CCTA group had coronary atherosclerosis (CCTA positive). Medication use was increased in the CCTA-positive group compared with both the CCTA-negative (no atherosclerosis) and control groups at 90 days (statin use, 34% vs 5% vs 8%, respectively; aspirin use, 40% vs 5% vs 8%, respectively), and 18 months (statin use, 20% vs 3% vs 6%, respectively; aspirin use, 26% vs 3% vs 6%, respectively). After multivariable risk adjustment, the odds ratios for statin and aspirin use in the CCTA-positive group at 18 months were 3.3 (95% confidence interval [CI], 1.3-8.3) and 4.2 (95% CI, 1.8-9.6), respectively. At 90 days, in the total CCTA group vs controls, there were more secondary tests (55 [5%] vs 22 [2%]; P < .001) and revascularizations (13 [1%] vs 1 [0.1%]; P < .001). One cardiovascular event occurred in each group over 18 months.

CONCLUSIONS: An abnormal screening CCTA result was predictive of increased aspirin and statin use at 90 days and 18 months, although medication use lessened over time. Screening CCTA was associated with increased invasive testing, without any difference in events at 18 months. Screening CCTA should not be considered a justifiable test at this time.

PMID: 21606093

CT Coronary Plaque Burden in Asymptomatic Patients With Familial Hypercholesterolaemia

OBJECTIVES:  To determine the calcium score and coronary plaque burden in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH) compared with a control group of patients with low probability of coronary artery disease, having non-anginal chest pain, using CT.

METHODS: Design, setting and patients 101 asymptomatic patients with FH (mean age 53±7 years; 62 men) and 126 patients with non-anginal chest pain (mean age 56±7 years; 80 men) underwent CT calcium scoring and CT coronary angiography. All patients with FH were treated with statins during a period of 10±8 years before CT. The coronary calcium score and plaque burden were determined and compared between the two patient groups.

RESULTS: The median total calcium score was significantly higher in patients with FH (Agatston score=87, IQR 5–367) than in patients with non-anginal chest pain (Agatston score=7, IQR 0–125; p<0.001). The overall coronary plaque burden was significantly higher in patients with FH (p<0.01). Male patients with FH, whose low-density lipoprotein cholesterol levels were reduced by statins below 3.0 mmol/l, had significantly less coronary calcium (p<0.01) and plaque burden (p=0.02).

CONCLUSIONS: The coronary plaque burden is high in asymptomatic middle-aged patients with FH despite intense statin treatment.

PMID:

Prognostic Value and Determinants of a Hypointense Infarct Core in T2-Weighted Cardiac Magnetic Resonance in Acute Reperfused ST-Elevation Myocardial Infarction

OBJECTIVES: A hypointense core of infarcted myocardium in T2-weighted cardiovascular MR (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. Aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation myocardial infarction (STEMI).

METHODS: We analyzed 346 STEMI patients undergoing primary angioplasty <12 hours after symptoms onset. T2-weighted and contrast-enhanced CMR was used for assessment of the area-at-risk, myocardial salvage, infarct size, hypointense core in T2-weighted images and late microvascular obstruction (MO). Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. Primary endpoint of the study was occurrence of major adverse cardiovascular events (MACE) defined as death, reinfarction and congestive heart failure within 6 months after infarction.

RESULTS: A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of MO, less myocardial salvage and impaired left ventricular (LV) function (p<0.001, respectively). The presence of a hypointense core was a strong univariable predictor of MACE (hazard ratio: 2.59, confidence interval: 1.27-5.27) and was significantly associated with an increased MACE rate (16.4% versus 7.0%, p=0.006) six months after infarction.

CONCLUSIONS: A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, MO and impaired LV function with subsequent adverse clinical outcome.

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Cardiac Magnetic Resonance Imaging in Dilated Cardiomyopathy in Adults—Towards Identification of Myocardial Inflammation

OBJECTIVES: To assess active myocardial inflammation by cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB) amongst adult patients with dilated cardiomyopathy (DCM).

METHODS: We evaluated 23 adults with chronic DCM, who had successfully undergone both CMR and EMB within 3.5 ± 2.6 days. EMB was considered the gold standard. CMR assessment of myocardial inflammation used the following parameters as recommended by the recently published “Lake Louise Criteria”: global myocardial oedema, global relative enhancement (RE), and late gadolinium enhancement (LGE). According to “Lake Louise Criteria”, myocardial inflammation was diagnosed if two or more of the three above-mentioned parameters were positive.

RESULTS: Myocardial inflammation was confirmed by immunohistology in 12 patients (52.2%). Sensitivity, specificity, and diagnostic accuracy of CMR to detect immunohistologically confirmed myocardial inflammation were 75.0%, 72.7%, and 73.9%, respectively. Sensitivity, specificity, and diagnostic accuracy of the individual CMR parameters to detect myocardial inflammation were as follows: global myocardial oedema, 91.7%, 81.8%, and 87.0%, respectively; global RE, 58.3%, 63.6%, and 60.9%, respectively; LGE, 58.3%, 45.4%, and 52.2%, respectively.

CONCLUSIONS: Global myocardial oedema was identified as a promising CMR parameter for assessment of myocardial inflammation in patients with DCM. In these patients, global myocardial oedema yielded superior diagnostic performance compared to “Lake Louise Criteria”.

PMID: 20963443

Incremental Prognostic Significance of Combined Cardiac Magnetic Resonance Imaging, Adenosine Stress Perfusion, Delayed Enhancement, and Left Ventricular Function Over Pre-imaging Information for the Prediction of Adverse Events

OBJECTIVES: Although cardiac magnetic resonance imaging (CMR) is capable of yielding extensive data in routine practice, the relative incremental prognostic value of adenosine stress perfusion, myocardial delayed enhancement (DE), and left ventricular volumes and function is unclear.

METHODS: We followed up 908 consecutive patients who underwent combined CMR for suspicion of coronary stenosis and/or ischemia at 2.6±1.2 years, during which 101 total cardiac events occurred (all-cause death, myocardial infarction, or late revascularization). Increase in Cox proportional-hazards model global χ(2) (χ(2)) with the addition of CMR data after adjustment for clinical data defined incremental prognostic value.

RESULTS: Cardiac magnetic resonance imaging without abnormalities had a 2.4% event rate per year (<1% cardiac death or myocardial infarction). Abnormal CMR was associated with event rates of 5.6% to 7.0% per year, varying with which and how many components were abnormal. After adjusting for the pre-CMR data (age, dyspnea, prior coronary artery disease, resting heart rate, renal disease, and diabetes mellitus, χ(2):43.6, P<0.0001; C index 0.695), the addition of left ventricular ejection fraction, aortic flow, delayed enhancement, and stress perfusion data all incrementally increased χ(2) (55.2, 63.3, 68.0, and 68.9, respectively; all P<0.00001; C indices 0.717, 0.722, 0.747, and 0.736). The number of abnormal CMR domains both added incremental prognostic value and risk stratified patients with respect to risk of events.

CONCLUSIONS: CMR analysis of ventricular volume, aortic flow, myocardial viability, and stress perfusion all add incremental value for prediction of adverse events over pre-CMR data and can be combined to further enhance prognostication. Normal combined CMR confers a low risk of subsequent cardiac events.

PMID: 21444886