Real-time phase contrast magnetic resonance imaging for assessment of haemodynamics: from phantom to patients.

OBJECTIVES: Assessment of haemodynamics is crucial in many cardiac diseases. Phase contrast MRI (PC-MRI) can accurately access it. Arrhythmia is a major limitation in conventional segmented PC-MRI (SEG). A real-time PC-MRI sequence (RT) could overcome this. We validated RT by comparing to SEG. METHODS: A prototype RT using shared velocity encoding was tested against SEG at 1.5 T in a flow phantom and consecutively included patients with (n = 55) or without (n = 59) aortic valve disease. In patients with atrial fibrillation (Afib, n = 15), only RT was applied. Phantom: PC images were acquired in front of and behind an interchangeable aortic-stenosis-like inlay. Mean velocity and flow were quantified. PATIENTS: PC images were acquired in the ascending aorta, pulmonary trunk and superior caval vein. Peak velocity, stroke volume and regurgitant fraction were quantified. RESULTS: Phantom: Mean velocities (11 ± 1 to 207 ± 10 cm/s) and flow correlated closely between SEG and RT (r ≥ 0.99, ICC ≥ 0.98, p < 0.0005). Patients without AVD or with aortic regurgitation: Concordance of SEG and RT was excellent regarding peak velocities, stroke volumes (r ≥ 0.91, ICC ≥ 0.94, p < 0.0005) and regurgitant fractions (r = 0.95, ICC = 0.95, p < 0.0005). RT was feasible in all patients with Afib. CONCLUSIONS: The real-time sequence is accurate compared to conventional segmented PC-MRI. Its applicability in Afib was shown. Real-time PC-MRI might become a valuable tool in arrhythmia. KEY POINTS: • Assessment of haemodynamics is crucial in many cardiac diseases. • Arrhythmias are a major limitation of conventional techniques in cardiac magnetic resonance. • A real-time technique, which allows application in arrhythmia, was validated. • This real-time technique might become a valuable tool in arrhythmic patients.

Current T1 and T2 mapping techniques applied with simple thresholds cannot discriminate acute from chronic myocadial infarction on an individual patient basis: a pilot study.

BACKGROUND: Studying T1- and T2-mapping for discrimination of acute from chronic myocardial infarction (AMI, CMI). METHODS: Eight patients with AMI underwent CMR at 3 T acutely and after >3 months. Imaging techniques included: T2-weighted imaging, late enhancement (LGE), T2-mapping, native and post-contrast T1-mapping. Myocardial T2- and T1-relaxation times were determined for every voxel. Abnormal voxels as defined by having T2- and T1-values beyond a predefined threshold (T2 > 50 ms, native T1 > 1250 ms and post-contrast T1 < 350 ms) were highlighted and compared with LGE as the reference. RESULTS: Abnormal T2-relaxation times were present in the voxels with AMI (=> delete acute infarction; unfortunately this is not possible in your web interface) acute infarction only in half of the subjects. Abnormal T2-values were also present in subjects with CMI, thereby matching the chronically infarcted territory in some. Abnormal native T1 times were present in voxels with AMI in 5/8 subjects, but also remote from the infarcted territory in four. In CMI, abnormal native T1 values corresponded with infarcted voxels, but were also abnormal remote from the infarcted territory. Voxels with abnormal post-contrast T1-relaxation times agreed well with LGE in AMI and CMI. CONCLUSIONS: In this pilot-study, T2- and T1-mapping with simple thresholds did not facilitate the discrimination of AMI and CMI.

Assessment of nonischemic fibrosis in hypertrophic cardiomyopathy: comparison of gadopentetate dimeglumine and gadobenate dimeglumine for enhanced cardiovascular magnetic resonance imaging.

PURPOSE: To compare whether the higher relaxivity contrast agent gadobenate is superior for the identification of nonischemic late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) compared to standard relaxivity agents such as gadopentetate. MATERIALS AND METHODS: Fifteen patients with HCM and positive LGE based on routine cardiac magnetic resonance (CMR) with 0.2 mmol/kg gadopentetate were enrolled. Each patient thereafter underwent a second enhanced CMR exam with 0.2 mmol/kg gadobenate using the same CMR protocol. LGE was assessed in a short axis stack acquired after contrast administration using an inversion recovery gradient echo sequence. Two independent blinded readers quantified LGE by manual planimetry. The signal intensities of injured myocardium, remote myocardium, left ventricular cavity, and air were measured in identical locations using anatomical landmarks and dedicated software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. RESULTS: No adverse events related to contrast administration occurred. Gadobenate dimeglumine showed a higher SNR of injured myocardium (45.4 ± 24.0 vs. 31.1 ± 16.6, P = 0.002) and a higher CNR between remote and injured myocardium (37.6 ± 25.0 vs. 26.5 ± 17.6, P = 0.006) compared to gadopentetate dimeglumine. The amount of LGE (based on the same postprocessing criteria and definitions) was higher with gadobenate dimeglumine (12.7 ± 8.5 g vs. 9.4 ± 5.6 g, P = 0.005). There was no difference in intra- and interobserver variability between gadopentetate dimeglumine and gadobenate dimeglumine. CONCLUSION: CMR with the high relaxivity contrast agent gadobenate dimeglumine reveals significantly more tissue with LGE in patients with HCM.

Regioselective analysis of heat-induced conformational changes of ß-lactoglobulin by quantitative liquid chromatography-mass spectrometry analysis of chemical labeling kinetics.

ß-Lactoglobulin is a main allergen in cow's milk; its allergenicity is strongly impacted by processing. To understand heat-induced epitope-specific effects, the present study analyzed regiospecific conformational changes of heated native ß-lactoglobulin variant A (BLG-A). Complementary fluorescence spectroscopy methods indicated two denaturation phases comprising minor sequential conformational changes (25-75 °C) and complete transitions (80-90 °C). Regioselective conformational changes of BLG-A in the native state (25 °C), sequential (70 °C) and complete transition (90 °C) were determined by quantitative liquid chromatography-mass spectrometry analysis of chemical labeling kinetics covering 14 lysine residues and the N-terminus. Conformational changes in two phases were observed for N-terminus, K8 (both N-terminal chain), K60 (ß-sheet C), K75 (ß-sheet D), K77 (DE loop), K83 (ß-sheet E), K100 and K101 (FG loop). The residues K14 (ß-sheet A1), K47 (ß-sheet B), K69, K70 (both ß-sheet D), and K91 (ß-sheet F) were not involved in conformational changes.

Variability and homogeneity of cardiovascular magnetic resonance myocardial T2-mapping in volunteers compared to patients with edema.

BACKGROUND: The aim of the study was to test the reproducibility and variability of myocardial T2 mapping in relation to sequence type and spatial orientation in a large group of healthy volunteers. For control T2 mapping was also applied in patients with true edema. Cardiovascular magnetic resonance (CMR) T2-mapping has potential for the detection and quantification of myocardial edema. Clinical experience is limited so far. The variability and potential pitfalls in broad application are unknown. METHODS: Healthy volunteers (n = 73, 35 ± 13 years) and patients with edema (n = 28, 55 ± 17 years) underwent CMR at 1.5 T. Steady state free precession (SSFP) cine loops and T2-weighted spin echo images were obtained. In patients, additionally late gadolinium enhancement images were acquired. We obtained T2 maps in midventricular short axis (SAX) and four-chamber view (4CV) based on images with T2 preparation times of 0, 24, 55 ms and compared fast low angle shot (FLASH) and SSFP readout. 10 volunteers were scanned twice on separate days. Two observers analysed segmental and global T2 per slice. RESULTS: In volunteers global myocardial T2 systematically differed depending on image orientation and sequence (FLASH 52 ± 5 vs. SSFP 55 ± 5 ms in SAX and 57 ± 6 vs. 59 ± 6 ms in 4CV; p < 0.0001 for both). Anteroseptal and apical segments had higher T2 than inferior and basal segments (SAX: 59 ± 6 vs. 48 ± 5 ms for FLASH and 59 ± 7 vs. 52 ± 4 ms for SSFP; p < 0.0001 for both). 14 volunteers had segments with T2 ≥ 70 ms. Mean intraobserver variability was 1.07 ± 1.03 ms (r = 0.94); interobserver variability was 1.6 ± 1.5 ms (r = 0.87). The coefficient of variation for repeated scans was 7.6% for SAX and 6.6% for 4CV. Mapping revealed focally increased T2 (73 ± 9 vs. 51 ± 3 ms in remote myocardium; p < 0.0001) in all patients with edema. CONCLUSIONS: Myocardial T2 mapping is technically feasible and highly reproducible. It can detect focal edema and differentiate it from normal myocardium. Increased T2 was found in some volunteers most likely due to partial volume and residual motion.

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

UNLABELLED: Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. CONCLUSION: A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet.

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

AIMS: Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD. METHODS AND RESULTS: We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E', invasive LV end-diastolic pressure, and N-terminal pro-brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD- (total number 41). DD+ showed enlarged LA with LA end-diastolic volume/height performing best to identify DD+ with a cut-off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD-: -14.5 ± 6.5%/s vs. DD+: -10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD-: -4.2 ± 1.6%/s vs. DD+: -3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD-: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD-: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD-: -3.6 ± 0.7 ms vs. DD+: -2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD-: -5.0 ± 1.8 ms vs. DD+: -3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD-: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD-. CONCLUSIONS: Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD.

Gender-specific differences in left ventricular remodelling and fibrosis in hypertrophic cardiomyopathy: insights from cardiovascular magnetic resonance.

BACKGROUND: Gender is an independent risk factor for heart failure mortality in hypertrophic cardiomyopathy (HCM). AIMS: To explore the interaction between gender, myocardial fibrosis and remodelling in HCM. METHODS: We studied 64 HCM patients (28 females, aged 51+/-16 years) categorized as non-obstructive (HNCM, n=31) or obstructive (HOCM, n=33) and 60 healthy subjects (31 females, aged 43+/-14 years). Cine imaging was performed to assess left ventricular volumes and mass. LV remodelling index (LVRI) was calculated. Extension of late gadolinium enhancement (LGE) was quantified. RESULTS: Females in the control group and in the HNCM group had a lower LVRI than males (control: 0.7+/-0.1 vs. 0.9+/-0.2 g/ml, p<0.002; HNCM: 1.1+/-0.2 vs. 1.5+/-0.5 g/ml, p<0.001). In contrast, HOCM females had a similar LVRI compared to males (1.8+/-0.5 vs. 1.7+/-0.4 g/ml, p=ns). Thus the increase in LVRI was more pronounced in females compared to males. LGE was noted in 70% of the patients. No relation was found between the presence or the quantity of myocardial fibrosis and gender in any of the patient subgroups. CONCLUSION: Our data suggest a disproportionate degree of remodelling in different forms of HCM depending on gender. Gender does not appear to influence the quantity of fibrosis as defined by LGE.

Structure-selectivity investigations of D2-like receptor ligands by CoMFA and CoMSIA guiding the discovery of D3 selective PET radioligands.

Elucidation of the physiological role of the D3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D3 selectivity over both congeners D2 and D4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q2cv(D3/D2) = 0.86; q2cv(D3/D4) = 0.92) and excellent predictions of a 16-ligand test set (r2pred = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D3 affinities and considerable selectivities over D2 and D4 and, subsequently, to the subtype selective PET tracers [18F]78 and [18F]79.

Blood oxygen level-dependent MRI of tissue oxygenation: relation to endothelium-dependent and endothelium-independent blood flow changes.

OBJECTIVES: The contribution of endothelial function to tissue oxygenation is not well understood. Muscle blood oxygen level-dependent MRI (BOLD MRI) provides data largely dependent on hemoglobin (Hb) oxygenation. We used BOLD MRI to assess endothelium-dependent signal intensity (SI) changes. METHODS AND RESULTS: We investigated mean BOLD SI changes in the forearm musculature using a gradient-echo technique at 1.5 T in 9 healthy subjects who underwent a protocol of repeated acetylcholine infusions at 2 different doses (16 and 64 microg/min) and N(G)-monomethyl-L-arginine (L-NMMA; 5 mg/min) into the brachial artery. Sodium nitroprusside was used as a control substance. For additional correlation with standard methods, the same protocol was repeated, and forearm blood flow was measured by strain gauge plethysmography. We obtained a significant increase in BOLD SI during acetylcholine infusion (64 microg/min) and a significant decrease for L-NMMA infusion (P<0.005 for both). BOLD SI showed a different kinetic signal than did blood flow, particularly after intermittent ischemia and at high flow rates. CONCLUSIONS: In standard endothelial function tests, BOLD MRI detects a dissociation of tissue Hb oxygenation from blood flow. BOLD MRI may be a useful adjunct in assessing endothelial function.

Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

BACKGROUND: Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance. METHODS AND RESULTS: Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients). CONCLUSIONS: In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities.

CoMFA and CoMSIA investigations revealing novel insights into the binding modes of dopamine D3 receptor agonists.

As an extension of a series of dopamine D(3) receptor agonists involving FAUC 54, ex-chiral pool synthesis, and biological evaluation of 3-substituted 7-aminotetrahydroindolizines was performed. Considering the structural features of both series of enantiomers, we developed a novel alignment hypothesis for D(3) agonists, allowing for the placement of the aromatic moieties on two alternative, adjacent positions. CoMFA and CoMSIA analyses yielded significant cross-validated q(2) values of 0.726 and 0.590, respectively, when a newly invented program application (IRAS) controlling the alignment selection proved to be useful. Employing the CoMFA/CoMSIA contribution maps, we were able to transform a previously constructed homology model of the D(3) receptor from an inactive into an activate state. Besides the established ionic interactions, we propose pi-stacking with Phe6.51 and a hydrogen bond between His6.55 and the acyl moiety to be primarily involved in the D(3) receptor binding of FAUC 54 and its analogues.

Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients.

OBJECTIVE: Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients. METHODS: Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms. RESULTS: The average weight reduction of 9.1 ±â€Š3.8  kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51 ±â€Š24 vs. 53 ±â€Š24  pmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss. CONCLUSIONS: We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.

Clinical effects of phosphodiesterase 3A mutations in inherited hypertension with brachydactyly.

Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator-stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population.

Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12.

This study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation end-products (RAGE). Binding of MGO-modified S100A12 to RAGE decreased significantly with increasing MGO concentration and incubation time. Ca(2+)-induced S100A12 hexamerization was impaired only at higher MGO concentrations indicating that the loss of affinity is not predominantly caused by disturbance of ligand oligomerization. nePTM mapping showed carboxyethylation of lysine (CEL) and the N-terminus without preferential modification sites. Besides, hydroimidazolone, hemiaminals, argpyrimidine, and tetrahydropyrimidine rapidly formed at R21. Even at the highest modification rate, hexamerization of synthesized CEL-S100A12 was unaffected and RAGE-binding only slightly impaired. Thus, nePTMs at R21 seem to be the major cause of MGO-induced impairment of S100A12 oligomerization and RAGE binding.

Cardiac magnetic resonance imaging of congenital bicuspid aortic valves and associated aortic pathologies in adults.

AIMS: Bicuspid aortic valve (BAV) represents the most frequent congenital cardiac abnormality resulting in premature valvular degeneration and aortic dilatation. In a large series of consecutive patients, we evaluated the distribution of BAV types and the associated valvular and aortic abnormalities. METHODS AND RESULTS: We investigated 266 patients (58 ± 14 years) with BAV using a 1.5 T cardiac magnetic resonance (CMR) scanner. Valve morphology was described according to the Sievers classification. The aortic valve orifice area, aortic regurgitation (AR) fraction, and aortic dilation were quantified. Two hundred and forty-two data sets were available for analysis; 24% had BAV without a valvular lesion. The predominant valvular lesion was aortic stenosis (AS) with 51%. Lone AR was found in 17%. A combined lesion of AS and AR was found in 9%. Those with AS were older than the overall average (64 ± 12 vs. 57 ± 15 years, P < 0.001). The patients with AR and those without valvular abnormality were younger than average (49 ± 13 and 50 ± 12 years vs. 57 ± 15 years, P < 0.01 respectively). Comparing two observers Kappa coefficient was 0.77 for differentiation of six valve morphologies and 0.80 for the differentiation of bicuspid and tricuspid valve. Aortic dilatation was found in 39% of cases with no discernible preference for any specific BAV-type and mainly affecting the ascending aorta. CONCLUSION: CMR can non-invasively differentiate various morphologies in BAV with low inter-observer variability. Valvular pathologies vary across age. Aortic dilatation is frequent in BAV independent from valvular morphology or lesion. In future CMR might help to guide management in patients with BAV.

Long-lasting improvements in liver fat and metabolism despite body weight regain after dietary weight loss.

OBJECTIVE: Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. RESEARCH DESIGN AND METHODS: We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17-36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. RESULTS: Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. CONCLUSIONS: A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions.

Fatty acid binding protein 4 predicts left ventricular mass and longitudinal function in overweight and obese women.

OBJECTIVE: To explore whether increased adipocyte-derived serum fatty acid binding protein 4 (FABP4) predisposes to cardiac remodelling and left ventricular dysfunction in human obesity. DESIGN: Cross-sectional investigation. SETTING: Academic clinical research centre. PATIENTS: 108 overweight and obese non-diabetic women (body-mass index 33 ± 5 kg/m2). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Relationship between serum FABP4 and abdominal adipose tissue quantified by MRI. Relationship between serum FABP4 and left ventricular morphology and function assessed by cardiac MRI. RESULTS: FABP4 was independently associated with visceral abdominal adipose tissue (ß=0.34, p<0.01) and subcutaneous abdominal adipose tissue (ß=0.22, p<0.05). After stratification into serum FABP4 tertiles, left ventricular masses were 92 ± 16 g, 86 ± 13 g and 81 ± 12 g in women with high, intermediate and low FABP4 concentrations (p<0.01), respectively. Longitudinal systolic function was reduced by 8% in women with intermediate and high versus low FABP4 concentrations (p<0.01), whereas ejection fraction did not differ among tertiles (p=0.5). In multivariate linear analysis FABP4 remained an independent predictor of left ventricular mass (ß=0.17, p<0.05) and reduced longitudinal fractional shortening (ß=0.21, p<0.05). CONCLUSIONS: In overweight and obese women, FABP4 showed an independent association with parameters of left ventricular remodelling.

Moderate dietary weight loss reduces myocardial steatosis in obese and overweight women.

BACKGROUND: Excessive myocardial triglyceride (MTG) content in obesity and type 2 diabetes is associated with impaired cardiac function. Previous studies suggest that MTG could be mobilized through lifestyle interventions. We assessed influences of moderate dietary weight loss in non diabetic obese and overweight women on MTG content and cardiac function. METHODS: We selected a subgroup of 38 women from the B-SMART study population. The B-SMART study compared weight loss and associated metabolic and cardiovascular markers with reduced-carbohydrate and reduced-fat hypocaloric diets. Selected subjects had completed a cardiac magnetic resonance (MR) scan including imaging and proton spectroscopy to assess cardiac structure and function as well as MTG content. RESULTS: An average weight reduction of 5.4 ± 4.3 kg at six months was associated with a relative decrease of MTG of 25% (from 0.72 ± 0.29% at baseline to 0.54 ± 0.23% at follow-up, p<0.001). The response was similar with carbohydrate and fat restriction. Diastolic function expressed as ratio of peak filling rate in E- and A-Phase (PFRE/PFRA) was unchanged. Reductions of left atrial size (from 21.9 ± 4.0 cm(2) to 20.0 ± 3.7 cm(2), p=0.002), the normalized ratio of PFRE and early diastolic lengthening velocity PLV (from 8.2 ± 2.6 to 7.5 ± 2.5, p<0.001) and fat free mass (from 55.1 ± 6.9 kg to 52.7 ± 6.5 kg, p=0.007) reflected altered cardiac volume loading after diet, but did not correlate to MTG content. CONCLUSIONS: Moderate dietary weight loss significantly reduced MTG content in women with uncomplicated overweight or obesity. Macronutrient composition of the diet did not significantly affect the extent of MTG reduction.