Grigorios Korosoglou

Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque

Objective To understand the determinants of troponin release in patients with stable coronary artery disease (CAD) by comparing high sensitive troponin T (hsTnT) levels with computed tomography angiography (CTA) characteristics of atherosclerotic plaque. Methods hsTnT was determined in 124 consecutive patients with stable angina, who underwent clinically indicated 256-slice CTA for suspected CAD. CTA was used to assess (1) coronary calcification; (2) stenosis severity; (3) non-calcified plaque volume; (4) plaque composition (soft or mixed, described as ‘non-calcified’ versus calcified) and (5) the presence of vascular remodeling in areas of non-calcified plaque. Results All CT scans were performed without adverse events, and diagnostic image quality was achieved in 1830/1848 available coronary segments (99.0%). In 29/124 patients, hsTnT was ≥14 pg/ml (range 14.0–34.4). Weak, albeit significant, correlations were found between hsTnT and calcium scoring (r=0.45, p<0.001), while a stronger correlation was found between hsTnT and the total non-calcified plaque burden (r=0.79, p<0.001). Patients with non-calcified plaque (n=44) yielded significantly higher hsTnT values than those with normal vessels (n=46) or those with only calcified lesions (n=26), (12.6±5.2 vs 8.3±2.6 and 8.8±3.0 pg/ml, respectively, p<0.001). Furthermore, those with remodeled non-calcified plaque (n=8) showed even higher hsTnT values of 26.3±6.5 pg/ml than all other groups (p<0.001). This allowed the identification of patients with remodeled non-calcified plaque by hsTnT with high accuracy (area under the curve=0.90, SE=0.07, 95% CI 0.84 to 0.95). Conclusions Chronic clinically silent rupture of non-calcified plaque with subsequent microembolisation may be a potential source of troponin elevation. In light of recent imaging studies, in which patients with positively remodeled non-calcified plaque were shown to be at high risk for developing acute coronary syndromes, hsTnT may serve as a biomarker for such ‘vulnerable’ coronary lesions even in presumably stable CAD.

Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

OBJECTIVES The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. BACKGROUND AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. METHODS Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. RESULTS After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p < 0.0001), diastolic dysfunction (p < 0.01), the pathologic free light chains (p < 0.05), cardiac troponin-T (cTnT) (p < 0.01), and the Karnofsky index (p < 0.001) remained as independent predictors. 2D-GLS delineated a superior prognostic value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers. CONCLUSIONS In the largest serial investigation reported so far, reduced LV longitudinal function served as an independent predictor of survival in AL amyloidosis and offered incremental information beyond standard clinical and serological parameters.

Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy

Objective Owing to its variable clinical course, risk stratification is of paramount importance in non-ischaemic dilated cardiomyopathy (DCM). The goal of this study was to investigate the long-term prognostic significance of late gadolinium enhancement (LGE) as detected by contrast-enhanced cardiovascular magnetic resonance (CE-CMR) in patients with DCM. Design Observational cohort study. Setting University hospital. Patients 184 consecutive patients with DCM. Measurements CE-CMR was performed on a 1.5 T clinical scanner. Presence, extent and patterns of LGE were determined by two independent observers. Outcome measures Patients were followed for the composite end point of cardiac death, hospitalisation for decompensated heart failure, or appropriate implantable cardioverter defibrillator discharge for a mean±SEM of 685±30 days. Results LGE was detected in 72/184 patients (39%) and was associated with a lower left ventricular (LV) ejection fraction (31% (20.9–42.2%) vs 44% (33.1–50.9%), p<0.001), higher LV end-diastolic volume index (133 (116–161) ml/m2 vs 109 (92.7–137.6) ml/m2, p<0.001) and higher LV mass (80 (67.1–94.8) g/m2 vs 65.8 (55.2–82.9) g/m2, p<0.001). Patients in whom LGE was present were more likely to experience the composite end point (15/72 vs 6/112, p=0.002). Receiver operating characteristic curve analysis revealed a LGE of >4.4% of LV mass as optimal discriminator for the composite end point. When entered into multivariate Cox regression analysis, LGE retained its independent predictive value, yielding an associated HR of 3.4 (95% CI 1.26 to 9). Conclusion The presence of LGE in this large DCM patient cohort is associated with pronounced LV remodelling, functional impairment and an adverse outcome. Further research is necessary to determine whether these findings will aid the clinical management of DCM patients.

Noninvasive Detection of Macrophage-rich Atherosclerotic Plaque in Hyperlipidemic Rabbits using ‘Positive Contrast’ Magnetic Resonance Imaging

OBJECTIVES This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Assessment of myocardial deformation with cardiac magnetic resonance strain imaging improves risk stratification in patients with dilated cardiomyopathy.

AIMS To investigate the prognostic impact of left-ventricular (LV) cardiac magnetic resonance (CMR) deformation imaging in patients with non-ischaemic dilated cardiomyopathy (DCM) compared with late-gadolinium enhancement (LGE) quantification and LV ejection fraction (EF). METHODS AND RESULTS A total of 210 subjects with DCM were examined prospectively with standard CMR including measurement of LGE for quantification of myocardial fibrosis and feature tracking strain imaging for assessment of LV deformation. The predefined primary endpoint, a combination of cardiac death, heart transplantation, and aborted sudden cardiac death, occurred in 26 subjects during the median follow-up period of 5.3 years. LV radial, circumferential, and longitudinal strains were significantly associated with outcome. Using separate multivariate analysis models, global longitudinal strain (average of peak negative strain values) and mean longitudinal strain (negative peak of the mean curve of all segments) were independent prognostic parameters surpassing the value of global and mean LV radial and circumferential strain, as well as NT-proBNP, EF, and LGE mass. A global longitudinal strain greater than -12.5% predicted outcome even in patients with EF < 35% (P < 0.01) and in those with presence of LGE (P < 0.001). Mean longitudinal strain was further investigated using a clinical model with predefined cut-offs (EF < 35%, presence of LGE, NYHA class, mean longitudinal strain greater than -10%). Mean longitudinal strain exhibited an independent prognostic value surpassing that provided by NYHA, EF, and LGE (HR = 5.4, P < 0.01). CONCLUSION LV longitudinal strain assessed with CMR is an independent predictor of survival in DCM and offers incremental information for risk stratification beyond clinical parameters, biomarker, and standard CMR.

Age- and gender-related normal left ventricular deformation assessed by cardiovascular magnetic resonance feature tracking.

BackgroundAssessment of left (LV) ventricular function is one of the most important tasks of cardiovascular magnetic resonance (CMR). Impairment of LV deformation is a strong predictor of cardiovascular outcome in various cardiac diseases like ischemic heart disease or cardiomyopathies. The aim of the study was to provide reference values for myocardial deformation derived from the CMR feature tracking imaging (FTI) algorithm in a reference population of healthy volunteers.MethodsFTI was applied to standard short axis and 2-, 3- and 4-chamber views of vector-ECG gated CMR cine SSFP sequences of 150 strictly selected healthy volunteers (75 male/female) of three age tertiles (mean age 45.8yrs). Global peak and mean radial, circumferential and longitudinal endo- and myocardial systolic strain values as well as early diastolic strain rates were measured using FTI within a standard protocol on a 1.5T whole body MR scanner.ResultsGlobal peak systolic values were 36.3 ± 8.7% for radial, −27.2 ± 4.0% for endocardial circumferential, −21.3 ± 3.3% for myocardial circumferential, −23.4 ± 3.4% for endocardial longitudinal and −21.6 ± 3.2% for myocardial longitudinal strain. Global peak values were -2.1 ± 0.5s−1 for radial, 2.1 ± 0.6s−1 for circumferential endocardial, 1.7 ± 0.5s−1 for circumferential myocardial, 1.8 (1.5-2.2)s−1 for longitudinal endocardial, 1.6 (1.4-2.0)s−1 for longitudinal myocardial early diastolic strain rates. Men showed a higher radial strain than women whereas the circumferential and longitudinal strains were lower resulting in less negative values. Circumferential and longitudinal strain rates were significantly higher in female subjects. Radial strain increased significantly with age whereas the diastolic function measured by the radial, circumferential and longitudinal strain rates showed a decrease.The coefficients of variation determined in ten further subjects, who underwent two CMR examinations within 12 days, were −4.8% for circumferential and −4.5% for longitudinal endocardial mean strains.ConclusionsMyocardial deformation analysis using FTI is a novel technique and robust when applied to standard cine CMR images providing the possibility of a reliable, objective quantification of global LV deformation. Since strain values and strain rates differed partly between genders as well as between age groups, the application of specific reference values as provided by this study is recommendable.

Real-time fast strain-encoded magnetic resonance imaging to evaluate regional myocardial function at 3.0 Tesla: Comparison to conventional tagging

To compare the utility of the real‐time technique fast strain‐encoded magnetic resonance imaging (fast‐SENC) for the quantification of regional myocardial function to conventional tagged magnetic resonance imaging (MRI).

Strain-Encoded CMR for the Detection of Inducible Ischemia During Intermediate Stress

OBJECTIVES This study sought to evaluate the diagnostic accuracy of strain-encoded cardiac magnetic resonance (SENC) for the detection of inducible ischemia during intermediate stress. BACKGROUND High-dose dobutamine stress cardiac magnetic resonance (DS-CMR) is a well-established modality for the noninvasive detection of coronary artery disease (CAD). However, the assessment of cine scans relies on the visual interpretation of wall motion, which is subjective, and modalities that can objectively and quantitatively assess the time course of myocardial strain response during stress are lacking. METHODS Stress-induced ischemia was assessed by wall motion analysis and by SENC in 80 patients with suspected or known CAD and in 18 healthy volunteers who underwent DS-CMR in a clinical 1.5-T scanner. Quantitative coronary angiography was used as the standard reference for the presence of CAD (> or =50% diameter stenosis). RESULTS On a patient level, 46 of 80 patients (58%) had CAD, including 20 with single-vessel, 18 with 2-vessel, and 8 with 3-vessel disease. During peak stress, SENC correctly detected ischemia in 45 versus 38 of 46 patients with CAD (7 additional correct findings for SENC), yielding significantly higher sensitivity than cine (98% vs. 83%, p < 0.05). No patients were correctly diagnosed by cine and missed by SENC. During intermediate stress, SENC showed diagnostic value similar to that provided by cine imaging only during peak dobutamine stress (sensitivity of 76% vs. 83%, specificity of 88% vs. 91%, and accuracy of 81% vs. 86%; p = NS for all). Quantification analysis demonstrated that strain rate response is a highly sensitive marker for the detection of inducible ischemia (area under the curve = 0.96; SE = 0.01; 95% confidence interval: 0.93 to 0.99) that precedes the development of inducible wall motion abnormalities and already significantly decreases with moderate 40% to 60% coronary lesions. CONCLUSIONS Using SENC, CAD can be detected during intermediate stress with similar accuracy to that provided by cine only during peak stress. By this approach, patient safety may be improved during diagnostic procedures within lower time spent (Strain-Encoded Cardiac Magnetic Resonance Imaging for Dobutamine Stress Testing; NCT00758654).

Urinary Adiponectin Excretion: A Novel Marker for Vascular Damage in Type 2 Diabetes

OBJECTIVE Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30–70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 ± 14.26 vs. control subjects: 2.91 ± 3.85 μg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (β = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events.

Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve

To study myocardial perfusion reserve and myocellular metabolic alterations indicated by triglyceride content as possible causes of diastolic dysfunction in patients with type 2 diabetes mellitus, preserved systolic function, and without clinically evident coronary artery disease.