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To the Editor: In the present study we sought to investigate the predictive value of resting and inducible wall motion abnormalities (WMA) and of late gadolinium enhancement (LGE) for hard cardiac outcomes and for revascularization procedures in 3,138 patients undergoing dobutamine cardiac magnetic

Objectives We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD). Methods and Results 177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing ≥50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing 3 risk factors, presence of CAD, hs-CRP and hs-TnT. Conclusion Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD.

Summary The detailed molecular mechanisms following activation of apoptosis in ischemia-reperfusion injury are unknown. This study using different transgenic mouse models provided first evidence that apoptosis in myocardial ischemia-reperfusion injury is rather linked to the mitochondrial pathway than to death receptor pathway. Introduction There is a wealth of evidence for activation of apoptosis in ischemia-reperfusion injury. However, the understanding of detailed molecular mechanism is lacking. Methods The extent of myocardial infarction after ligation of the left anterior descending artery in mice carrying different transgenes for inhibition of either the intrinsic or the extrinsic or a combination of both apoptotic cascades was evaluated. The extent of myocardial damage was assessed by echocardiographic determination of left ventricular (LV) ejection fraction, LV hemodynamics, troponin T, and histology. The rate of apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining. Results Highest perioperative rate of death was observed in the dominant-negative form of a truncated Fas-associated death domain (FADD-DN) group. Infarction size by 2,3,5-triphenyltetrazolium chloride (TTC) staining was smaller in the Bcl-2, but not in the other groups as compared to wild-type mice. This was accompanied by lower troponin T values in Bcl-2 transgenic mice as compared to the all other groups. Troponin T correlated well with macroscopic extent of myocardial infarction by TTC staining. A lower decline of LV ejection fraction was seen in the Bcl-2 as compared to wild-type or FADD-DN mice. A smaller number of TUNEL- and caspase-3-positive myocyte nuclei were observed in the Bcl-2 and FADD-DN group as compared to wild-type mice. Conclusions We provide first evidence for protective effects on the myocardium in a transgenic mouse model of myocardial ischemia-reperfusion due to inhibition of the Bcl-2, but not the FADD pathway despite that reduced apoptotic cells were observed in both groups as compared to wild-type mice.

Background Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy. Methods 19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months. Results Five patients were not followed up for reasons of death (n = 2), discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (−12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p

The purpose of our study was to investigate whether the quantification of myocardial blush grade (MBG) during surveillance coronary angiography can predict long-term outcome after heart transplantation (HT). In 105 HT recipients who underwent cardiac catheterization, cardiac allograft vasculopathy (CAV) was assessed visually using the ISHLT grading scale (prospective cohort study). MBG was quantified by dividing the plateau of contrast agent gray-level intensity (G(max)) by the time-to-peak intensity (T(max)). In a subgroup (n = 72), myocardial perfusion index by cardiac magnetic resonance imaging (CMR) was assessed. During a mean follow-up duration of 2.7 (standard deviation [SD] 1.0) years, 26 patients experienced cardiac events, including 7 with cardiac death and 19 who underwent coronary revascularization. G(max)/T(max) was related to CAV by ISHLT criteria and to subsequent cardiac events. By univariate analysis, patient age, organ age, CAV, MBG and myocardial perfusion index by CMR were all predictive for cardiac events. Multivariable analysis demonstrated that G(max)/T(max) provided the most robust prediction of cardiac death (hazard ratio [HR] = 0.2, 95% confidence interval [CI] = 0.06-0.64, p < 0.01) and cardiac events (HR = 0.52, 95% CI = 0.32-0.84, p < 0.01), beyond clinical parameters and the presence of CAV. G(max)/T(max) is a valuable surrogate parameter of microvascular integrity, which is associated with cardiac death and revascularization procedures after HT.

Background Mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) correlate with the left and right ventricular (LV,RV) ejection fraction as well as with the prognosis of patients with heart failure. Furthermore, M/TAPSE are sensitive markers for impaired longitudinal function which can be the earliest marker of myocardial dysfunction in cardiomyopathies with preserved ejection fraction. Cardiac MRI is the reference method for ventricular function and morphology and both M/TAPSE can be easily obtained from cine images. To date, there are no age and gender specific reference values for M/TAPSE derived from a healthy collective of normal volunteers. In this study we want to provide reference values for M/TAPSE for cardiac MRI with regard to age and gender. Methods 60 male and 59 female healthy volunteers were divided into three age groups (I=20-34yrs, II=35-49yrs, III≥50yrs). Images were acquired on a 1.5T whole body MRI scanner (Philips Achieva) using a SSFP sequence of short axis slices covering the entire left ventricle as well as two-, three- and four-chamber views. M/TAPSE were measured on 4-chamber SSFP images. Two separate reference lines were drawn in diastole and systole from the basal lateral tricuspid (TAPSE) and the basal anterior mitral leaflet (MAPSE) to a reference point on the left chest surface. The lengths differences of the reference lines between diastole and systole were measured and represent both M/TAPSE. P

Background The high prevalence of cardiovascular abnormalities in patients (pts.) with systemic lupus erythematosus (SLE) results in an increased risk of premature cardiovascular events. Inflammatory and immunological processes have been associated with the pathogenesis of myocardial necrosis and dysfunction, however only scarce data exists on cardiac tissue characterization. Non-invasive gadolinium contrast-enhanced cardiovascular MRI (CEMRI) offers the ability to identify micro-vascular noninfarct-specific inflammatory processes in combination with myocardial functional assessment. We sought to investigate the utility of cardiac MRI (CMR) for functional and morphological tissue characterisation in SLE pts. Methods

Summary We could show that PC-CMR analysis of DD is clinically feasible and showed excellent agreement with the widely accepted EC parameters for classification of DD. PC-CMR could offer the potential of a practically and reasonably time-consuming approach for the clinically important assessment of DD with CMR. Background Over the last decade the interest in diastolic dysfunction has grown, due to the fact that at least half of all cases of newly diagnosed heart failure patients present with preserved ejection fraction. One of the most important tasks of cardiovascular imaging is the objective assessment of left ventricular (LV) systolic and diastolic function, which is routinely performed with standard transthoracic echocardiography (EC). In EC, classification of diastolic dysfunction (DD) is widely accepted and mainly assessed using three criteria: mitral blood flow (MBF, EA-curve), lateral wall velocity (LWV, S-E-A-curve) and pulmonary vein flow (PVF, S-D-AR-curve). With these three characteristic flow and velocity patterns and their ratios E/A, E/E and S/D, regular diastolic function can be clearly distinguished. Cardiovascular magnetic resonance (CMR) has excellent capabilities to assess blood flow and myocardial tissue motion using phase contrast (PC-CMR) imaging. We sought to compare the feasibility of PC-CMR with echocardiographic doppler imaging for the assessment of DD using the echocardiographic flow and velocity approach for DD-classification. Methods After acquisition of regular short axis cine SSFP volumetry and 2-3-4-chamber views in 38 patients with various cardiovascular diseases, we performed single-slice short-axis PC-CMR (60phases,velocity-encoding=100cm/ s) similarly to typical EC locations at the tip of mitral leaflets in diastole on a 1.5T whole body MRI system (Philips Achieva) to generate mitral E-and A-waves, lateral S`-E`-A-velocities, E/A- and E/E`-ratios. PC-CMR for PVF was planned orthogonally to the cine 4-chamber plane 1cm distal from pulmonary vein inflow into the left atrium. Directly after MRI, EC was performed to generate complementary data for MBF, LWV and PVF. Results EC and PC-CMR could be performed in all patients, whereas EC PVF could not be assessed in 8 patients due to reduced flow signals. Correlation with mitral E and A velocities was good (r=0.72 and 0.74, p

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.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.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.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 (p0.0001), diastolic dysfunction (p0.01), the pathologic free light chains (p0.05), cardiac troponin-T (cTnT) (p0.01), and the Karnofsky index (p0.001) 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; p0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p0.01). LS and 2D-GLS both offered significant incremental information (p0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers.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.

Fabian aus dem Siepen,1 Ralf Bauer,1 Matthias Aurich,1 Sebastian J Buss,1 Henning Steen,1 Klaus Altland,2 Hugo A Katus,1 Arnt V Kristen1 1Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany; 2Institute of Human Genetics, Justus-Liebig-University, Giessen, Germany Background: Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE). Methods: Twenty-five male patients (71 [64; 80] years) with wtATTR-CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI) (n=14), and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months. Results: A significant decrease of left ventricular (LV) myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03) by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006) was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75), LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; P=0.1), and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3) by echocardiography remained unchanged. Conclusion: This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction. Keywords: wild-type ATTR, cardiomyopathy, polyphenol, EGCG

The attenuation of adverse myocardial remodeling and pathological left ventricular (LV) hypertrophy is one of the hallmarks for improving the prognosis after myocardial infarction (MI). The protein kinase Akt plays a central role in regulating cardiac hypertrophy, but the in vivo effects of chronic pharmacological inhibition of Akt are unknown. We investigated the effect of chronic Akt blockade with deguelin on the development of pathological [MI and aortic banding (AB)] and physiological (controlled treadmill running) hypertrophy. Primary cardiomyocyte cultures were incubated with 10 μmol deguelin for 48 h, and Wistar rats were treated orally with deguelin (4.0 mg·kg−1·day−1) for 4 wk starting 1 day after the induction of MI or AB. Exercise-trained animals received deguelin for 4 wk during the training period. In vitro, we observed reduced phosphorylation of Akt and glycogen synthase kinase (GSK)-3β after an incubation with deguelin, whereas MAPK signaling was not significantly affected. In vivo, treatment with deguelin led to attenuated phosphorylation of Akt and GSK-3β 4 wk after MI. These animals showed significantly increased heart weights and impaired LV function with increased end-diastolic diameters (12.0 ± 0.3 vs. 11.1 ± 0.3 mm, P < 0.05), end-diastolic volumes (439 ± 8 vs. 388 ± 18 μl, P < 0.05), and cardiomyocyte sizes (+20%, P < 0.05) compared with MI animals receiving vehicle treatment. Furthermore, activation of Ca2+/calmodulin-dependent kinase II in deguelin-treated MI animals was increased compared with the vehicle-treated group. Four wk after AB, we observed an augmentation of pathological hypertrophy in the deguelin-treated group with a significant increase in heart weights and cardiomyocyte sizes (>20%, P < 0.05). In contrast, the development of physiological hypertrophy was inhibited by deguelin treatment in exercise-trained animals. In conclusion, chronic Akt blockade with deguelin aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy.

Aims Autoimmunity against cardiac troponin I (cTnI) has deleterious effects on the infarcted myocardium early after onset of ischaemia. Here, we explored the impact of cTnI-autoimmunity in the long term. Furthermore, we studied the effects of cTnI-autoimmunity on the infarcted myocardium following revascularization measures in terms of ischaemia reperfusion injury (IRI), which resembles clinical reality more closely. Methods and results After immunization with either cTnI (n= 10) or a control buffer (n= 14), A/J mice underwent chronic coronary artery ligation. Another group of mice immunized with cTnI (n= 13) underwent temporary coronary artery occlusion and were compared with non-immunized controls (n= 17). Left ventricular function was evaluated by echocardiography. Hearts were obtained for histological evaluation. Immunological responses were quantified by analysis of cytokine and chemokine patterns as well as anti-cTnI antibody titres. Myocardial inflammation and cardiac dysfunction were detectable as late as 180 days after myocardial infarction (MI). Previous cTnI-immunization enhanced myocardial inflammation and dysfunction. Mice subjected to cTnI-immunization before IRI exhibited a higher inflammation score, an upregulated expression of pro-inflammatory chemokines (IP-10, MIP-1, Ltn, RANTES, TCA-3) and chemokine receptors (CCR2, CCR5), increased interleukin (IL)-2, interferon (IFN)-g, and decreased IL-10 production along with a markedly reduced fractional shortening after IRI compared with the controls. Conclusion Our results demonstrate for the first time that cTnI-induced autoimmune response not only leads to increased myocardial inflammation and impaired cardiac function 180 days after chronic coronary artery ligation, but also exacerbates ischaemia/reperfusion injury compared with non-immunized controls. Hence, the presence of cTnI-autoimmunity could render subjects more vulnerable to prospective myocardial injury, be it MI, or secondary revascularization measures.

Evaluation of left ventricular function (LV) is one of the most important tasks of echocardiography. Left ventricular longitudinal function has been recognized to differentiate myocardial disorders better than ejection fraction (EF) alone. But recent parameters are still dependent on image quality and time consuming.Transthoracic echocardiography, tissue Doppler imaging, strain imaging and assessment of longitudinal function with a tissue motion annular displacement (TMAD) tracking algorithm were performed in 152 patients with various cardiac pathologies and 47 healthy volunteers in a clinical routine setting.Measures of longitudinal function such as LV peak systolic strain (SR, r² = 0.88, p 0.001) and peak systolic strain rate (SRR, r² = 0.78, p 0.001) correlated highly with TMAD. Tissue motion annular displacement was ultrafast and less time-consuming compared to strain imaging (8.2 ± 2.2 s, p 0.001). Significantly more patients with reduced image quality could be analyzed compared to strain imaging (p 0.001). The intra- and inter-observer variabilities were very low with 1.3 ± 1% and 1.7 ± 1.2%. Tissue motion annular displacement correlated well with clinical parameters (NYHA, r = -0.71, p 0.001) as well as NT-proBNP (r = -0.73, p 0.001) and identified patients with structural heart disease with a significantly higher sensitivity 92.1% and specificity 95.7% than did EF, SR, SRR or NT-proBNP (Cut-off:14.2%, p 0.01). In a subgroup of patients with systemic light chain amyloidosis and preserved EF (50%, n = 54), TMAD was significantly reduced, especially in those without any signs of cardiac involvement and was superior to other parameters of longitudinal function (p 0.05).Tissue motion annular displacement is a rapid, sensitive and reproducible method for the assessment of LV longitudinal function, which is less dependent on image quality.

Purpose: 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. Materials and Methods: Patients with type 2 diabetes mellitus (n = 42) underwent cardiac magnetic resonance (CMR) for quantification of 1) myocardial contractility by strain-encoded MR (SENC); 2) myocardial triglyceride content by proton magnetic resonance spectroscopy (1H-MRS); and 3) myocardial perfusion reserve during pharmacologic hyperemia. Age-matched healthy volunteers (n = 16) also underwent CMR to acquire normal values for myocardial strain and perfusion reserve. Results: Stress CMR procedures were successfully performed in all subjects, and no regional inducible perfusion defects were observed in type 2 diabetes mellitus patients. Diastolic strain rate and myocardial perfusion reserve were significantly impaired in patients with type 2 diabetes mellitus compared to control subjects (P < 0.001 for both). Interestingly, impaired diastolic function in type 2 diabetes mellitus was not associated with impaired myocardial perfusion reserve (r = 0.12, P = NS). Conversely a significant association was observed between diastolic dysfunction and myocardial triglyceride content (r = −0.71, P < 0.001), which proved to be independent of age, gender, diabetes duration, blood pressure, and fasting blood glucose. Conclusion: Myocardial steatosis may represent an early marker of diabetic heart disease, triggering subclinical myocardial dysfunction irrespective of myocardial perfusion reserve. J. Magn. Reson. Imaging 2012;35:804–811. © 2011 Wiley Periodicals, Inc.

Right-anterior-oblique (RAO) monoplane cineventriculography is usually applied in cardiac catheter labs to assess the left ventricular (LV) function. However, it is uncertain whether this technique is reliable in clinical routine. Unenhanced two-dimensional echocardiography was reported to underestimate left ventricular volumes. The aim of this study was to compare these two conventional techniques with cardiac magnetic resonance imaging (MRI), the present gold standard for the determination of LV function, to evaluate whether the results from the conventional techniques are reliable and in accordance with each other. Seventy-two patients were retrospectively recruited and analysis of the three techniques was performed. Compared with MRI, RAO cineventriculography underestimated LV end-systolic volumes (ESV), and overestimated LV ejection fraction (EF); two-dimensional echocardiography underestimated LV end-diastolic volume (EDV) and EF. Correlation coefficients on EDV, ESV, and EF were 0.8806, 0.9201, and 0.8864 between echocardiography and MRI (P < 0.01, for all), followed by 0.7718, 0.8835, and 0.7785, between cineventriculography and MRI (P < 0.01, for all), and 0.7006, 0.7680, and 0.7644 between cineventriculography and echocardiography (P < 0.01, for all). Echocardiography and MRI showed the highest inter-technique correlation coefficients, and the narrowest Bland-Altman limits of agreement for EDV, ESV and EF. EDV, ESV and EF determined by RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography and MRI were in high accordance with each other, with wide variances between the techniques. Although not interchangeable, RAO monoplane cineventriculography, unenhanced two-dimensional echocardiography, and cardiac MRI are reliable tools in clinical routine for the assessment of LV volumes and function.

The purpose of this study was to determine the prognostic value of strain-encoded magnetic resonance imaging (SENC) during high-dose dobutamine stress cardiac magnetic resonance imaging (DS-MRI) compared with conventional wall motion readings.Detection of inducible ischemia by DS-MRI on the basis of assessing cine images is subjective and depends on the experience of the readers, which may influence not only the diagnostic classification but also the risk stratification of patients with ischemic heart disease.In all, 320 consecutive patients with suspected or known coronary artery disease underwent DS-MRI, using a standard protocol in a 1.5T MR scanner. Wall motion abnormalities (WMA) and myocardial strain were assessed at baseline and during stress, and outcome data including cardiac deaths, nonfatal myocardial infarctions ("hard events"), and revascularization procedures performed90 days after the MR scans were collected.Thirty-five hard events occurred during a 28 ± 9 month follow-up period, including 10 cardiac deaths and 25 nonfatal myocardial infarctions, and 32 patients underwent coronary revascularization. Using a series of Cox proportional-hazards models, both resting and inducible WMA offered incremental information for the assessment of hard cardiac events compared to clinical variables (chi-square = 13.0 for clinical vs. chi-square = 26.1 by adding resting WMA, p0.001, vs. chi-square = 39.3 by adding inducible WMA, p0.001). Adding visual SENC or quantitative strain rate reserve to this model further improved the prediction of outcome (chi-square = 50.7 vs. chi-square = 52.5, p0.001 for both). In a subset of patients (n = 175) who underwent coronary angiography, SENC yielded significantly higher sensitivity for coronary artery disease detection (96% vs. 84%, p0.02), whereas specificity and accuracy were not significantly different (88% vs. 94% and 93% vs. 88%, p = NS for both).Strain-encoded MRI aids the accurate identification of patients at high risk for future cardiac events and revascularization procedures, beyond the assessment of conventional atherogenic risk factors and resting or inducible WMA on cine images. (Strain-Encoded Cardiac Magnetic Resonance Imaging as an Adjunct for Dobutamine Stress Testing; NCT00758654).

The extent of adverse myocardial remodeling contributes essentially to the prognosis after myocardial infarction (MI). Currently, therapeutic strategies that inhibit remodeling are limited to inhibition of neurohumoral activation. mTOR-dependent signaling mechanisms are centrally involved in the myocardial remodeling process. There exists a controversy as to whether autophagy is beneficial in the setting of myocardial infarction. We now provide evidence that induction of autophagy by inhibition of mTOR with everolimus (RAD) prevents adverse left ventricular remodeling and limits infarct size following myocardial infarction. mTOR inhibition increases autophagy and concomitantly decreases proteasome activity especially in the border zone of the infarcted myocardium. The induction of autophagy via mTOR inhibition is a novel potential therapeutic approach to limit infarct size and to attenuate adverse left ventricular remodeling following MI.

Sustained left ventricular hypertrophy (LVH) accelerates cardiac dysfunction and heart failure. Previous reports have suggested that activation of the peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent pathway is involved in development of cardiac hypertrophy. Thiazolidinediones (TZDs) such as pioglitazone activate PPARgamma and are clinically used as antidiabetics. Given inconsistent reports regarding effects of TZDs on LVH, we examined in the present study the influence of pioglitazone on LVH in a rat model of aortic banding. Aortic banding was induced in rats by clipping the ascending aorta. Animals received pioglitazone (3 mg/kg/day) or placebo. Echocardiographic, hemodynamic, histological, and biochemical measurements were performed after 2 and 4 weeks. Pressure gradient was comparable between pioglitazone- and placebo-treated animals after 2 and 4 weeks. Left ventricular function was not different between the groups. In sham as well as in banded animals, LV/body weight ratio was increased in pioglitazone- as compared to placebo-treated animals after 2 and 4 weeks. Furthermore, an increase in myocyte size and atrial natriuretic factor was observed in pioglitazone- compared to placebo-treated animals 4 weeks after aortic banding as well. The results of this study demonstrate that activation of PPARgamma via pioglitazone does not protect the myocardium from pressure overload-induced LVH in a rat model of aortic banding. The findings rather indicate a pro-hypertrophic effect of pioglitazone treatment after aortic banding.

Amyloid light chain (AL) amyloidosis is a rare disease with poor prognosis and limited therapeutic alternatives. Recently, one clinical case with cardiac involvement, as well as a compelling evidence of green tea polyphenol, epigallocatechin-3-gallate (EGCG), inducing the formation of benign aggregation products that do not polymerize into fibrils were published. This is a report of the cardiac effects of green tea consumption in these patients. Patients with known cardiac involvement in AL amyloidosis were examined by routine cardiovascular examinations that took place every 3–6 months. Of 59 patients with cardiac involvement, 11 revealed a decrease of at least 2 mm of interventricular wall thickness, after initiation of regular green tea consumption (GT). A matched historic control group (n = 22) was selected. Comprehensive echocardiography was conducted at every control examination and analyzed offline by two independent examiners. GT patients showed an improvement in New York Heart Association (NYHA) class from a median of 3 (25th, 75th percentiles: 2, 3) to 2 (2, 3), P = 0.038. Septal thickness decreased from 18 (18, 20) to 16 (16, 17) mm, P = 0.021. Left ventricular mass index decreased from 175 (154, 180) to 133 (128, 154) g/m2, P = 0.007. Comparing both groups, an increase in left ventricular ejection fraction could be found in the GT group, 65 (51, 73) versus 53 (47, 59)%, P = 0.012. These changes could not be observed in the control group. Consumption of green tea polyphenol EGCG in patients with cardiac involvement with AL amyloidosis causes a significant decrease in left ventricular wall thickness and mass, as well as an improvement in NYHA functional classification and left ventricular ejection fraction.

ObjectivesThe extent of adverse myocardial remodeling contributes essentially to the prognosis after myocardial infarction (MI). In this study we investigated whether inhibition of “mammalian target of rapamycin” (mTOR) attenuates left ventricular (LV) remodeling after MI.BackgroundTherapeutic strategies to inhibit remodeling are currently limited to inhibition of neurohumoral activation. The mTOR-dependent signaling mechanisms are centrally involved in remodeling processes and provide new therapeutic opportunities.MethodsEverolimus (RAD) treatment was initiated on the day after or 3 days after induction of myocardial infarction (MI) in rats.ResultsAfter 28 days, RAD-treated animals had reduced post-MI remodeling, with improved LV function and smaller LV end-diastolic diameters (8.9 ± 0.3 mm vs. 11.4 ± 0.2 mm, p < 0.05), end-diastolic volumes (304 ± 30 μl vs. 414 ± 16 μl, p < 0.05), and cardiac myocyte size (−40% vs. vehicle, p < 0.05). Infarct size was significantly reduced compared with vehicle-treated animals. The mTOR inhibition increased autophagy and concomitantly decreased proteasome activity in the border zone of the infarcted myocardium. Measurement of autophagic flux demonstrated that RAD did not decrease autophagosome clearance. When RAD treatment was initiated 3 days after MI, adverse remodeling was still attenuated and increased autophagy was still present. Sustained improvement of LV function was observed 3 months after MI, even when RAD treatment was discontinued after 1 month.ConclusionsInhibition of mTOR is a potential therapeutic strategy to limit infarct size and to attenuate adverse LV remodeling after MI.

Background—Despite the widespread use of cardiac troponins for diagnosis of myocyte injury and risk stratification in acute cardiac disorders, little is known about the long-term effects of the released troponins on cardiac function. Recently, we showed that an autoimmune response to cardiac troponin I (cTnI) induces severe inflammation and subsequent fibrosis in the myocardium. This autoimmune disorder predisposes to heart failure and cardiac death in mice.Methods and Results—To investigate the role of cTnI-specific T cells, T cells were isolated from splenocytes of mice immunized with murine cTnI (mcTnI). Wild-type mice that received mcTnI-specific T cells showed high mcTnI-specific antibody titers, increased production of the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α, severe inflammation and fibrosis in the myocardium, and reduced fractional shortening. To identify the antigenic determinants of troponin I responsible for the observed inflammation, fibrosis, and heart failure, 16 overlapping 16mer to 18mer peptides covering the entire amino acid sequence of mcTnI (211 residues) were synthesized. Only mice immunized with residues 105 to 122 of mcTnI developed significant inflammation and fibrosis in the myocardium, with increased expression of the inflammatory chemokines RANTES, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, macrophage inflammatory protein-2, T-cell activation-3, and eotaxin and the chemokine receptors CCR1, CCR2, and CCR5. Mice immunized with the corresponding human cTnI residues 104 to 121 and the mcTnI residues 131 to 148 developed milder disease.Conclusions—Transfer of troponin I–specific T cells can induce inflammation and fibrosis in wild-type mice, which leads to deterioration of contractile function. Furthermore, 2 sequence motifs of cTnI that induce inflammation and fibrosis in the myocardium are characterized.

BACKGROUND The ability to assess myocardial perfusion in small animals is important, especially to investigate models of myocardial ischemia. Myocardial perfusion is usually assessed by postmortem techniques, eliminating the possibility of follow-up in intervention studies. The purpose of the study was to examine the feasibility of real time myocardial contrast echocardiography (MCE) to evaluate cardioprotective effects of atorvastatin in a rat model of acute ischemia-reperfusion injury. METHODS The rats (n=15) underwent 20 minutes of mechanical left descending coronary artery (LAD) occlusion followed by 180 minutes of reperfusion. The animals received either atorvastatin (10 mg/kg), atorvastatin and the nitric oxide synthase (NOS)-inhibitor N-Nitro-L-Argininemethylester (L-NAME) (15 mg/kg), or vehicle. MCE was performed to assess the size of the perfusion defect and the myocardial signal intensities (A(max)) at the baseline, during occlusion, and during reperfusion. For comparison, the infarct size, risk area, and regional myocardial blood flow (MBF) were determined by the standard techniques as well. RESULTS The dynamics of ischemia-reperfusion injury could be visualized serially by MCE. The infarct size-to-risk area ratio progressively increased during reperfusion and was markedly reduced in the atorvastatin group. Triphenyltetrazolium chloride (TTC) staining confirmed a 23% reduction in the infarct size by atorvastatin. The infarct size by MCE correlated well with the histological methods (r=0.86, P < 0.001). A(max) was reduced in the anterior segments during LAD occlusion (0.08 +/- 0.01 dB) compared to the baseline (2.9 +/- 0.4 dB), approached higher levels post revascularization of LAD (3.22 +/- 0.50 dB), but decreased during 180 minutes of reperfusion (2.32 +/- 0.40 dB). After 180 minutes of reperfusion, A(max) in the risk area was significantly higher in the atorvastain-treated group compared to the vehicle-treated group (2.32 +/- 0.40 dB vs 1.3 +/- 0.4 dB, P

Background— High-mobility group box-1 (HMGB1) is a nuclear factor released by necrotic cells and by activated immune cells. HMGB1 signals via members of the toll-like receptor family and the receptor for advanced glycation end products (RAGE). Although HMGB1 has been implicated in ischemia/reperfusion (I/R) injury of the liver and lung, its role in I/R injury of the heart remains unclear. Methods and Results— Here, we demonstrate that HMGB1 acts as an early mediator of inflammation and organ damage in I/R injury of the heart. HMGB1 levels were already elevated 30 minutes after hypoxia in vitro and in ischemic injury of the heart in vivo. Treatment of mice with recombinant HMGB1 worsened I/R injury, whereas treatment with HMGB1 box A significantly reduced infarct size and markers of tissue damage. In addition, HMGB1 inhibition with recombinant HMGB1 box A suggested an involvement of the mitogen-activated protein kinases jun N-terminal kinase and extracellular signal-regulated kinase 1/2, as well as the nuclear transcription factor nuclear factor-κB in I/R injury. Interestingly, infarct size and markers of tissue damage were not affected by administration of recombinant HMGB1 or HMGB1 antagonists in RAGE −/− mice, which demonstrated significantly reduced damage in reperfused hearts compared with wild-type mice. Coincubation studies using recombinant HMGB1 in vitro induced an inflammatory response in isolated macrophages from wild-type mice but not in macrophages from RAGE −/− mice. Conclusions— HMGB1 plays a major role in the early event of I/R injury by binding to RAGE, resulting in the activation of proinflammatory pathways and enhanced myocardial injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy in I/R injury.

An 85-year-old woman was examined at the echocardiography laboratory during a predischarge examination after an uncomplicated, circumscribed acute myocardial infarction. An undefined liquid-containing mass (*) was observed behind the left atrium (LA), with no evidence of compression (panel A). This mass …

We thank Drs Conti and Volpe for their valuable comments regarding our article.1 We agree with their opinion that autoimmunity to troponins might have additional influence on the pathogenesis of cardiovascular diseases. In our recent publication, we describe how the induction of an immune response to troponin I (TnI) can induce a severe inflammation and fibrosis and then dilation and dysfunction of the myocardium. Furthermore, we show that preimmunization before the ligation of the left anterior descending artery …

Background CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. Methods and Results CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. Conclusions While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.

Methods 60 healthy volunteers, 60 patients with dilative cardiomyopathy, 40 patients with AL amyloidosis and 25 patients with hypertrophic cardiomyopathy underwent a CMR examination. 4 different techniques for the measurement of LAS were consecutively evaluated. Two of the techniques (LAS-epi/perp and LAS endo/perp) were assessed by measuring the distance between the epicardium or endocardium of the LV apex and a line connecting the origins of the mitral valve leaflets perpendicularly in end-diastole and end-systole. In the two other methods (LAS-epi/mid and LAS-endo/mid) the distance between the middle of the line connecting the mitral valvue leaflets and the epicardium or endocardium of the apex was measured in end-systole and end-diastole. Values for LAS for all techniques were finally assessed in percent according to the strain formula in 2 and 4 chamber views.

Mean GLS values were -16.2±5.3% and -17.3±5.3% for echocardiography and CMR, respectively. GLS did not differ significantly between the two imaging modalities, which showed strong correlation (r=0.86), a small bias (-1.1%) and narrow 95% limits of agreement (LOA, ±5.4%). Mean GCS values were -17.9±6.3% and -24.4 ±7.8% for echocardiography and CMR, respectively. GCS was significantly underestimated by echocardiography (p

Background Myocardial deformation analysis is an important task in the evaluation of heart failure. We and other previously showed that myocardial strain is a more sensitive marker for the prediction of cardiac events compared with leftventricular ejection-fraction (LV-EF). The current gold standard technique to quantify myocardial deformation is CMR tagging. However, additional pulse sequences and specialized software are necessary with tagging, so that alternative ways for the estimation of strain in CMR using conventional steady-state-free-precession (SSFP) cine images would be preferable. In this regards, feature tracking is a novel tool, which can be run on conventional cine images and can help estimating myocardial strain and strain rate without the need of specialized tagging sequences. The aim was to investigate the prognostic impact of myocardial strain using feature tracking cardiac magnetic resonance in patients with dilated cardiomyopathy. Methods Patients with dilated cardiomyopathy (n = 210) were examined in a 1.5T CMR-scanner. SSFP cine sequences of the three short and the three long axis views were analyzed using a prototype feature tracking software algorithm (2D CPA MR © ,T omTec Imaging Systems GmbH). Circumferential, longitudinal and radial strains were quantitatively assessed. Patient follow-up evaluation included the composite endpoint for the occurrence of cardiac death, heart transplantation and aborted sudden cardiac death. Patients were divided in subgroups by the appearance and absence of the composite endpoint, respectively, by left-ventricular ejection-fraction (LVEF≤35% and EF > 35%) and by the presence or absence of late gadolinium enhancement (LGE). Results The predefined primary endpoint, a combined endpoint of cardiac death, heart transplantation and aborted sudden cardiac death occurred in 26 subjects during the median follow-up period of 5.3 years. Global LV longitudinal strain < -12.5% was a significant predictor of survival. Using multivariable analysis global longitudinal strain exhibited an independent prognostic value for the composite endpoint surpassing the value of NYHA functional class, NT-proBNP, LV-EF, global LV radial and circumferential strain as well as LGE (HR = 1.23, p < 0.05). Reduced global longitudinal strain (≥-12.5%) was strongly predictive for worse outcomes even in patients with non-severely impaired LV-EF (≥35%; HR = 0.025, c 2 = 37.9, p < 0.001) and in those without LGE (HR = 0.12, c 2 = 12.7, p < 0.001). Global longitudinal strain < -12.5% on the other hand, predicted favorable outcome even in patients with severely impaired EF < 35% (HR = 0.21, c 2 = 7.9, p < 0.01) and in those with LGE (HR = 0.07, c 2 = 21.2, p < 0.001).

Background Recent reports indicate that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is potent to inhibit fibril formation of several amyloidogenic proteins in vitro. In vivo studies revealed reduction of left ventricular myocardial mass (LVM) after 12 months of daily consumption of 450 mg EGCG. However, the underlying process of LVM reduction, either due to reduction of amyloid or due to atrophy of cardiomyocytes, remained unknown. T1-mapping has the potential to monitor the extent of the extracellular volume (ECV). We sought to investigate the use of T1 mapping for monitoring of treatment effects in a cohort of patients with senile systemic amyloidosis (SSA) treated with EGCG for 12 months. Methods CMR examinations were performed in 8 patients (70 ± 8 years, 7 males) with histologically proven SSA before and 12 months after daily consumption of 450 mg EGCG using a 1.5 T CMR scanner (Achieva, Philips Healthcare). Short axis slices were acquired using SSFPsequences to measure left ventricular volumes, ejection fraction (EF) and LVM. T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times (TI; 100-4400 msec) using a single breathhold modified Look-Locker inversion-recovery sequence (MOLLI, TR/TE = 3,5/1,8 msec, flip angle = 35°) in late diastole before and 15 minutes after injection of gadolinium-DTPA contrast agent (0.2 mmol/kg body weight). ECV was calculated using the formula given in Figure 1. Results After 12 months of EGCG consumption a significant decrease of LVM (-14.5 ± 12.9 g, p < 0.05, Figure 2) was observed. Moreover, a significant decrease of native T1 (-63.3 ± 64.1 ms, p < 0.05, Figure 2) was noticed. There was no significant change in ECV and EF. Conclusions

Background The differentiation of left ventricular non-compaction (LVNC) from physiological trabeculation is still challenging as it may be overdiagnosed by current criteria. Therefore, we sought to investigate the effect of age and gender on both the LV and RV trabeculation in a large group of proven healthy subjects to provide adjusted reference values. Furthermore, we examined the correlation between the amount of non-compacted myocardium and the global ventricular function. Methods We studied a selected reference population of 117 healthy volunteers (58 male, 59 female) stratified into age tertiles (group 1 = 20-34 years, group 2 = 35-50 years, group 3 > 50 years) and by gender. Cardiac diseases were meticulously ruled out by taken medical history, physical examination, electrocardiography, oral glucose tolerance test and lab tests. Cardiovascular magnetic resonance images were acquired in a 1.5T whole-body MRI (Achieva, Philips Heathcare) using a standard SSFP sequence. Enddiastolic (EDV), end-systolic (ESV), stroke and trabeculated volumes as well as ejection fraction (EF) were quantified in short-axis views from base to apex. Volumes were indexed to body surface area (BSA). The noncompacted-to-compacted (NC/C)-ratio was measured in 4-chamber view. Results The left and right ventricular (LV/RV) trabeculated volumes were significantly larger in men than in women and decreased with age (LV: s = -0.1262, R 2 = 0.04450, p 2.3 in 28 of 117 subjects (23.9%) and > 2.5 in 26 of 117 subjects (22.2%), which is regarded as pathologic in current literature. The fraction of subjects with a NC/C ratio > 2.3 differed significantly between age but not between gender groups (p < 0.05, p = n.s). Likewise the mean NC/C ratio showed no significant differences between gender groups (1.9 ± 0.7 vs. 2.1 ± 0.8, p = n.s.) whereas subjects of the first tertile showed significant higher values than the volunteers of the second tertile (2.2 ± 0.8 vs. 1.8 ± 0.6, p < 0.05). An increasing NC/C

We present the case of a 37-year-old woman with hypertrophic cardiomyopathy, initially diagnosed at 23 years of age. The leading clinical problem is chest pain and inappropriate shortness of breath under exertion. When the patient was presented to our outpatient clinic for the first time at the age of 34 years, the coincidence of multiple lentigines (Figure 1), ECG changes (Figure 2), deafness, retardation in growth, hypertelorism, and strabism (operation at 21 years of age) were noted. Echocardiography and cardiac magnetic resonance imaging revealed a distinctive biventricular apical hypertrophy (Figures 3A, 3B, and 4⇓A and online-only Data Supplement Movies I and II). Interestingly, cardiac magnetic resonance imaging showed pronounced late gadolinium enhancement (Figure …

We describe a case of a male patient in whom a routine transthoracic echocardiography reveals a deep recessus of the muscular interventricular septum, without evidence of left-to-right shunt. The helical myocardial band, a new concept of myocardial architecture, could help in the interpretation of the genesis of this anatomic finding.

Background Assessment of left ventricular function (LV) is one of the most important tasks of clinical cardiac magnetic resonance imaging (CMR). Regional and global LV function has been recognized to differentiate various myocardial disorders. The aim of the study was to provide normal values for myocardial deformation parameters derived from the feature tracking imaging (FTI) algorithm applied to standard CMR cine SSFP sequences in a large group of healthy subjects. The feature tracking algorithm (2D CPA MR©, TomTec Imaging Systems GmbH), is a two dimensional deformation analysis of the myocardium that was originally designed for echocardiographic image analysis, which has now been transferred to CMR SSFP sequences without the need for additional scans. This novel approach may have potential advantages over existing methods, such as broad availability, vendor independency and lack of timeconsuming post processing.

Background The left ventricular (LV) ejection fraction (EF) is a crucial parameter for the diagnosis and therapeutic management of heart failure. Due to its wide availability and its comprehensive use, echocardiography (EC) is the standard method for the assessment of the LV function in clinical routine. As fundamental clinical decisions, e.g. initiation of medical heart failure therapy or implantation of an ICD, are based on the EF, methods like the Simpsons or Teichholz formulas have been developed for its quantification in EC. Cardiovascular magnetic resonance (CMR) is the gold-standard for the evaluation of cardiac function but comparative data between CMR and EC is scarce. Therefore, we sought to compare the agreement of functional EC and CMR measurements in a daily routine clinical setting.

Background Systemic light chain amyloidosis (AL) is associated with a high cardiovascular morbidity and mortality. Cardiovascular involvement and determination of prognosis is underestimated by standard imaging parameters. Recently, cardiac deformation analysis of global circumferential and longitudinal strain has been shown to have great clinical impact on the assessment of prognosis and survival in this rare disease. For quantification of cardiac deformation analysis we applied a novel non-invasive post-processing feature tracking algorithm (FTI) on pre-acquired regular CMR SSFP images in healthy volunteers and in patients with AL and sought to investigate wall motion differences between both groups. Methods 65 patients (mean age 58 ± 11 years; 41 male, 24 female patients) with biopsy proven systemic AL were scanned on a clinical 1.5 T CMR scanner (Philips Achieva). Short axis slices covering entirely both ventricles as well as 2-, 3- and 4-chamber were acquired using standard SSFP-sequences before initiation of specific pharmaceutical AL therapies. The control group consisted of 50 healthy subjects (mean age 58 ± 5 years; 23 male, 27 female). Besides the standard CMR parameters for volumes, ejection fraction (EF) and myocardial mass and wall thickness we measured global circumferential and longitudinal strain on SSFP images by the application of the post-processing feature tracking algorithm. Results Global circumferential strain and global longitudinal strain correlated well with left ventricular ejection fraction (r^2=0.64, p

Cardiac troponins are the most preferred markers of myocardial damage. The fact that they are normally not found in the circulation provides a high level of clinical sensitivity and specificity even when cardiac lesions are small. However, little is known about the long-term effects of the released troponins on cardiac function. In this study we prepared recombinant murine cardiac troponin I (mc-TnI) and murine cardiac troponin T and used them to immunize mice. We report that A/J mice immunized with mc-TnI developed severe inflammation of the myocardium with increased expression of inflammatory chemokines RANTES, MCP-1, MIP–1, MIP-1ß, MIP-2, TCA-3, and eotaxin and chemokine receptors CCR1, CCR2, and CCR5. The inflammation was followed by cardiomegaly, fibrosis, reduced fractional shortening, and 30% mortality over 270 days. In contrast, mice immunized with murine cardiac troponin T or with the control buffer showed little or no inflammation and no death. Furthermore, we demonstrate that mice preimmunized with mc-TnI before left anterior descending coronary artery ligation showed greater infarct size, more fibrosis, higher inflammation score, and reduced fractional shortening. Overall, our results show for the first time that provocation of an autoimmune response to mc-TnI induces severe inflammation in the myocardium followed by fibrosis and heart failure with increased mortality in mice.

Objectives We sought to evaluate noninvasive parameters by electrocardiography, echocardiography, technetium-99m–3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR). Background ATTR may present with highly variable symptoms, including polyneuropathy and cardiomyopathy, the latter being associated with a poor outcome. However, data on noninvasive risk stratification of ATTR are limited. Methods A total of 70 patients with ATTR were evaluated by echocardiography, cardiac biomarkers, and 99mTc-DPD scintigraphy. Cardiac magnetic resonance was performed in 30 patients. Echocardiographic findings and plasma levels of biomarkers were correlated with results of quantitative analysis of scintigraphy using a region-of-interest technique (whole-body as well as heart tracer retention). Receiver-operating characteristic (ROC) analysis was performed to calculate a cutoff value of 99mTc-DPD scintigraphy for heart retention for the diagnosis of cardiac amyloid involvement with the highest sensitivity and specificity. Univariate and multivariate analyses were performed in patients with cardiac involvement (n = 60) to determine noninvasive predictors of all-cause mortality. Results Scintigraphy findings correlated with morphological (interventricular septum thickness, left ventricular hypertrophy index) as well as functional (mitral annular systolic velocity, mitral/tricuspid annular plane systolic excursion) findings, cardiac biomarkers, renal function, and late gadolinium enhancement. The ROC-derived cutoff for the detection of cardiac amyloidosis by scintigraphic heart tracer retention was 4.8%. Univariate Cox regression revealed N-terminal pro–B-type natriuretic peptide, troponin T, mitral annular plane systolic excursion, and left ventricular hypertrophy index as predictors of all-cause mortality. However, on multivariate analysis, troponin T remained the only independent predictor of survival. The ROC-derived cutoff value of troponin T predicting all-cause mortality with the highest sensitivity (80.0%) and specificity (68.7%) was 0.0375 ng/l. Conclusions Quantitative analysis of tracer retention is capable of characterizing the severity of cardiac involvement in ATTR. By multivariate analysis, troponin T remained the only independent predictor of survival.

Background In clinical routine, quantification of myocardial strain using CMR tagging is currently the gold standard. Additional pulse sequences for the generation of tagged images and specialized software for the quantification of myocardial strain is necessary, so that alternative ways using conventional steady-state-free-precession (SSFP) sequence images would be preferable. This advantage may be ensured by feature tracking imaging algorithm, a novel method of two-dimensional deformation analysis. To quantify myocardial deformation with two-dimensional feature tracking cardiac magnetic resonance (CMR) in patients with heart failure due to nonischemic cardiomyopathy and in healthy controls. Methods Eighty-eight patients with dilated cardiomyopathy and thirty healthy subjects were examined in a 1.5T CMRscanner. SSFP cine sequences of the four chamber view and mid-ventricular short axis view were analyzed using feature tracking imaging software (2D CPA MR©, TomTec Imaging Systems GmbH). Generated parameters of the myocardial quantification were circumferential and longitudinal strain, respectively. Furthermore, patients were divided in subgroups classified by left-ventricular ejection-fraction LV-EF≤35% and EF>35% and in patients with the presence or absence of late-gadolinium enhancement (LGE), respectively. Results In patients with dilated cardiomyopathy, close correlation were observed for the LV-EF with circumferential strain (r^2=0.8, p 35% and with LV-EF ≤35% (p

Background: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. Methods and results: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Conclusion: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters.

Background Primary cardiac tumors are rare and often asymptomatic or present with unspecific symptoms. Benign cardiac tumors of vascular origin are especially rare, with only few existing data in the literature. Case presentation A 35-year-old Caucasian female patient presented to our department with an asymptomatic giant intracardiac angioma infiltrating both ventricles. Evaluation of this tumor involved electrocardiography, echocardiography, cardiac magnetic resonance imaging, coronary angiography, an open myocardial biopsy, and histological examination of the resected specimen. Because our patient was asymptomatic, she was managed conservatively with regular follow-up. We discuss the treatment options available in comparison with similar cases. Conclusion Diagnosis and therapy of benign cardiac tumors, especially of asymptomatic lesions, can be a challenge. There is no evidence available to help in the management of such patients. An extensive evaluation is needed with different imaging modalities, and case-specific decisions should be made that involve experts in cardiology, cardio-oncology, and heart surgery. Electronic supplementary material The online version of this article (doi:10.1186/s13256-016-0860-4) contains supplementary material, which is available to authorized users.

Background The objective assessment of global and regional cardiac function in children has shown to be clinically relevant but is challenging to conduct. Cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic modality especially in patients with cardiomyopathy or congenital heart disease. However, data on the normal cardiac deformation in children assessed by CMR is lacking at present. Thus, the aim of this study was to provide reference values for cardiac strain and strain rate in children and adolescents derived from CMR feature tracking (FT) measurements. Methods In this binational study, eighty children and adolescents (age 0.4–18.0 years, 41 male, 39 female) free from cardiac diseases from two centers underwent CMR in 1.5 T whole-body scanners in supine position. Global peak radial, circumferential and longitudinal systolic strains as well as the corresponding early peak diastolic strain rates were assessed applying FT on short axis as well as 3- and 4-chamber views of standard cine steady-state free precession images. Results The difference between genders yielded no significance for all assessed strains. Yet, all strains showed a significant parabolic relation to age and an even stronger one to body surface area (BSA). Therefore, BSA-specific reference values were determined using a polynomial regression model. The apical cardiac segments featured significant higher peak circumferential but lower peak radial systolic strains than the midventricular and basal segments (all p

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events.

Background Myocarditis is associated with a considerable morbidity and mortality in the acute phase as well as in the long term. It is found in up to 12% of young adults with sudden cardiac death and is regarded as a cause of dilated cardiomyopathy which is currently the most frequent reason for heart transplantation. Therefore, techniques for the diagnosis and the assessment of prognosis are of great interest. In this study we evaluate the novel post-procession feature tracking imaging (FTI) algorithm for strain analysis on patients with myocarditis. Methods We retrospectively included 36 patients (31 male, 5 female) who were admitted with acute myocarditis. A control group (31 male, 5 female) was drawn from a reference population of proven healthy volunteers and was matched with regard to age and gender. CMR imaging was performed on a 1.5 T whole-body MRI (Achieva, Philips Healthcare). Short axis views covering both ventricles as well as 2-, 3- and 4-chamber views were obtained using a SSFP sequence. Enddiastolic and endsystolic volumes as well as ejection fraction (EF) were derived from short axis segmentation. In addition we measured the circumferential und longitudinal strain applying a post-procession FTI algorithm (TomTec Imaging Systems). Results The study population and the control group showed similar characteristics regarding age and gender (40.3 ± 13.7 yrs. vs. 40.3 ± 15.7 yrs., p > 0.99). In patients with myocarditis the EF was significantly reduced compared to healthy controls (54.3 ± 8.4% vs. 67.8 ± 5.3%, p < 0.001). Furthermore the patients showed significantly lower values for the global circumferential strain (-24.4 ± 4.2% vs. -28.8 ± 3.8%, p < 0.001) as well as for the global longitudinal strain (-17.7 ± 4.5% vs. -23.6 ± 3.0%, p < 0.001). Global circumferential strain (r = -0.77, p < 0.001) and global longitudinal strain (r = -0.65, p < 0.001) correlated well with EF. In the subgroup of myocarditis patients with preserved ejection fraction (EF≥55%, 16 pts.) the global longitudinal strain (-20.4 ± 4.5% vs. -23.7 ± 2.6%, p < 0.05) was significantly reduced compared to the age- and gender matched control subgroup whereas the global circumferential strain did not show a significant difference (-27.3 ± 2.7% vs. -28.9 ± 3.8%, p = n.s.). Conclusions FTI strain analysis offers a fast quantitative assessment of myocardial strain patterns without the need for additional dedicated strain imaging sequences. Myocarditis patients with preserved EF show reduced longitudinal strain whereas the circumferential strain is not significantly

Background Similar to speckle tracking echocardiography cardiac MR (CMR) feature tracking imaging (FTI) uses a 2-dimensional deforming analysis of the myocardium which allows quantitative evaluation of myocardial motion and contractility. This technique might provide important additional information in children, including those with congenital heart disease (CHD). Until now, there are no reference data from a healthy pediatric population. The availability of this type of data is a requirement for proper interpretation in pediatric heart disease. The aim of this study was to determine normal values of left ventricular (LV) longitudinal, circumferential and radial strain and strain rate in healthy children, using FTI in cardiovascular MR images. Methods Eighty children from 2 centers (mean age: 12±5.5 years, range: 1t o 17 years; 39 female; divided into 3g roups: 0-11y (n=24), 11-15y (n=32), 15-18y (n=24)) were examined at two different 1.5 T scanners (Siemens and GE) using a standard SSFP MRI protocol. LV longitudinal, circumferential and radial strain and strain rate were measured using FTI (2D CPA MR©, TomTec Imaging System, Fulda, Germany). FTI was applied to standard cine-images in the following orientations:3 LV short-axis slices (basal, middle, apical), 4- and 3-chamber views. The effects of age, gender, endo- and epicardial assessment, myocardial segments on strain and strain rate data were also evaluated. Results