Wolfgang Utz

Cardiac magnetic resonance monitors reversible and irreversible myocardial injury in myocarditis

OBJECTIVES We sought to assess the value of cardiac magnetic resonance (CMR) to monitor the spectrum of myocarditis-related injuries over the course of the disease. BACKGROUND Myocarditis is associated with a wide range of myocardial tissue injuries, both reversible and irreversible. Differentiating these types of injuries is a clinical demand. METHODS We studied 36 patients (31 males, age 33 +/- 14 years) hospitalized with myocarditis during the acute phase and 18 +/- 10 months thereafter. CMR was performed on 2 1.5T scanners and included the following techniques: steady-state free precession (to assess left ventricular function and volumes), T2-weighted (myocardial edema), early (global relative enhancement [gRE], reflecting increased capillary leakage) and late T1-weighted after gadolinium-DTPA injection (late gadolinium enhancement [LGE], reflecting irreversible injury). RESULTS In the acute phase, T2 ratio was elevated in 86%, gRE in 80%, and LGE was present in 63%. At follow-up, ejection fraction increased from 56 +/- 8% to 62 +/- 7% (p < 0.0001) while both T2 ratio (2.4 +/- 0.5 to 1.9 +/- 0.2; p < 0.0001) and gRE (7.6 +/- 8 to 4.4 +/- 4; p = 0.018) significantly decreased. LGE persisted in all but 1 patient in whom LGE completely resolved. No patient had simultaneous elevation of T2 and gRE during the convalescent phase, resulting in a negative predictive value of 100% to differentiate the 2 phases of the disease. The acute phase T2 ratio correlated significantly with the change of end-diastolic volume over time (beta = 0.47; p = 0.008). This relation remained significant in a stepwise regression analysis model including T2 ratio, gRE, LGE extent, baseline ejection fraction, age, and creatine kinase, in which only T2 emerged as an independent predictor of the change in end-diastolic volume. CONCLUSIONS A comprehensive CMR approach is a useful tool to monitor the reversible and irreversible myocardial tissue injuries over the course of myocarditis and to differentiate acute from healed myocarditis in patients with still-preserved ejection fraction.

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

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. (HEPATOLOGY 2011)

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 &mgr;g/min) and NG-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 &mgr;g/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.

Myocardial steatosis, cardiac remodelling and fitness in insulin-sensitive and insulin-resistant obese women

Background Obesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is associated with myocardial triglyceride (MTG) accumulation. Lipotoxic injury from altered myocardial metabolism may be causative. Whether such association also exists in obese, non-diabetic women is unknown. Objective To explore the relation between MTG content, cardiac remodelling and cardiorespiratory fitness in obese, insulin-sensitive and insulin-resistant non-diabetic women. Design Cross-sectional investigation. Setting Academic clinical research centre. Patients 65 Overweight/obese and sedentary, but otherwise healthy women (body mass index 33±4 kg/m2; age 45±10 years). Interventions None. Main outcome measures Cardiac structure and function measured by cardiovascular magnetic resonance imaging and MTG content of the interventricular septum by 1H MR spectroscopy. Additional outcomes were cardiopulmonary fitness and insulin sensitivity during oral glucose tolerance testing. Results Insulin resistance (composite insulin sensitivity index (C-ISI) <4.6) was present in 29 women. MTG content was higher (0.83±0.30 vs 0.61±0.23, p=0.002) and left ventricular diastolic (p<0.01), but not systolic function was reduced in women with insulin resistance compared with insulin-sensitive women. The remodelling index defined as left ventricular mass divided by end-diastolic volume was increased in women with impaired glucose tolerance (p=0.006). Furthermore, cardiopulmonary fitness was equal in both groups, but was inversely correlated with MTG (r=−0.28, p=0.02). Conclusions In overweight and obese women, insulin resistance is associated with increased MTG content, cardiac remodelling and reduced diastolic function. Clinical Trial Registration ClinicalTrials.gov NCT00956566.

Contrast–dose relation in first‐pass myocardial MR perfusion imaging

To determine the regime of linear contrast enhancement in human first‐pass perfusion cardiovascular magnetic resonance (CMR) imaging to improve accuracy in myocardial perfusion quantification.

Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content

OBJECTIVE Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. RESEARCH DESIGN AND METHODS We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 ± 8.9 years, BMI 33.8 ± 4 kg/m2). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individuals CRF. Insulin sensitivity was determined during an oral glucose tolerance test. RESULTS For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = −0.27, P < 0.05), and visceral (r = −0.25, P < 0.05) and total fat mass (r = −0.32, P < 0.05), but not to intramyocellular lipids (r = −0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r2 = −0.43, P < 0.01, r2 = −0.34, and r2 = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. CONCLUSIONS Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction.

Left Ventricular Mass and Function With Reduced-Fat or Reduced-Carbohydrate Hypocaloric Diets in Overweight and Obese Subjects

In animals, carbohydrate and fat composition during dietary interventions influenced cardiac metabolism, structure, and function. Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity, we investigated whether these interventions differentially affect left ventricular mass, cardiac function, and blood pressure. We randomized 170 overweight and obese subjects (body mass index, 32.9±4.4; range, 26.5–45.4 kg/m2) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake. We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months. Ninety subjects completing the intervention period had a full cardiac MRI data set. Subjects lost 7.3±4.0 kg (7.9±3.8%) with reduced-carbohydrate diet and 6.2±4.2 kg (6.7±4.4%) with reduced-fat diet (P<0.001 within each group; P=not significant between interventions). Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets (5.4±5.4 g) or low-fat diets (5.2±4.8 g; P<0.001 within each group; P=not significant between interventions). Systolic and diastolic left ventricular function did not change with either diet. The 24-hour systolic blood pressure decreased similarly with both interventions. Body weight change (&bgr;=0.33; P=0.02) and percentage of ingested n-3 polyunsaturated fatty acids (&bgr;=−0.27; P=0.03) predicted changes in left ventricular mass. In conclusion, weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period. However, n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass.

Single- or dual-bolus approach for the assessment of myocardial perfusion reserve in quantitative MR perfusion imaging.

A dual‐bolus protocol can overcome limitations due to T1‐induced MR signal attenuation and hence enables more accurate quantification of myocardial blood flow (MBF) by contrast enhanced MR perfusion imaging. The study explores potential benefits of the dual‐bolus technique for the assessment of myocardial perfusion reserve (MPR) over a standard single‐bolus protocol. Nineteen patients without obstructive coronary artery disease as assessed by cardiac catheterization underwent a stress‐rest MR perfusion study using a dual‐bolus protocol. Gd‐DTPA dosages of 0.005 and 0.05 mmol/kg of bodyweight were delivered as pre‐ and main‐bolus. For comparison arterial input curves where extracted from left ventricular cavity passage including both, pre‐bolus and main‐bolus data. Global and segmental MPR were determined from semiquantitative and from full quantitative measures of MBF. As a result good agreement between dual‐ and single‐bolus technique was found with relative differences of maximally 10% in global MPR estimates. For the dual bolus approach a significant relative decrease of 30% (P < 0.001) was found for the coefficient of segmental MPR variation, which may allow a more reliable detection of hypoperfused segments in clinical studies. Magn Reson Med 59:1373–1377, 2008.

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.

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.