Introduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular... Show moreIntroduction: Carotid atherosclerotic intraplaque hemorrhage (IPH) predicts stroke. Patients with a history of stroke are treated with antiplatelet agents to prevent secondary cardiovascular events. A positive association between previous antiplatelet use and IPH was reported in a cross-sectional analysis. We investigated the changes in IPH over 2 years in patients who recently started versus those with continued antiplatelet use. Methods: In the Plaque at Risk (PARISK) study, symptomatic patients with <70% ipsilateral carotid stenosis underwent carotid plaque magnetic resonance imaging (MRI) at the baseline and after 2 years to determine IPH presence and volume. Participants were categorized into new users (starting antiplatelet therapy following the index event) and continued users (previous use of antiplatelet therapy before the index event). The association between previous antiplatelet therapy and the presence of IPH at baseline MRI was investigated using multivariable logistic regression analysis. The IPH volume change over a period of 2 years, defined as the difference in volume between follow-up and baseline, was investigated in each group with a Wilcoxon signed-rank test. The IPH volume change was categorized as progression, regression, or no change. Using multivariable logistic regression, we investigated the association between new antiplatelet use and (1) newly developed ipsilateral or contralateral IPH and (2) IPH volume progression. Results: A total of 108 patients underwent carotid MRI at the baseline and follow-up. At the baseline, previous antiplatelet therapy was associated with any IPH (OR = 5.6, 95% CI: 1.3–23.1; p = 0.02). Ipsilateral IPH volume did not change significantly during the 2 years in patients who continued receiving antiplatelet agents (86.4 mm3 [18.2–235.9] vs. 59.3 mm3 [11.4–260.3]; p = 0.6) nor in the new antiplatelet users (n = 31) (61.5 mm3 [0.0–166.9] vs. 27.7 mm3 [9.5–106.4]; p = 0.4). Similar results of a nonsignificant change in contralateral IPH volume during those 2 years were observed in both groups (p > 0.05). No significant associations were found between new antiplatelet use and newly developed IPH at 2 years (odds ratio [OR] = 1.0, 95% CI: 0.1–7.4) or the progression of IPH (ipsilateral: OR = 2.4, 95% CI: 0.3–19.1; contralateral: OR = 0.3, 95% CI: 0.01–8.5). Conclusion: Although the baseline association between IPH and previous antiplatelet therapy was confirmed in this larger cohort, the new onset of antiplatelet therapy after transient ischemic attack/stroke was not associated with the newly developed IPH or progression of IPH volume over the subsequent 2 years. Show less
Background: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve... Show moreBackground: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve during systole.Purpose: To assess multiphase segmentations and multiphase quantification of flow-related parameters in aortic 4D flow MRI.Study Type: Prospective.Population: 40 healthy volunteers (50% male, 28.9 +/- 5.0 years) and 10 patients with thoracic aortic aneurysm (80% male, 54 +/- 8 years).Field Strength/Sequence: 4D flow MRI with a velocity encoded turbo field echo sequence at 3 T.Assessment: Phase-specific segmentations were obtained for the aortic root and the ascending aorta. The whole aorta was segmented in peak systole. In all aortic segments, time to peak (TTP; for flow velocity, vorticity, helicity, kinetic energy, and viscous energy loss) and peak and time-averaged values (for velocity and vorticity) were calculated.Statistical Tests: Static vs. phase-specific models were assessed using Bland-Altman plots. Other analyses were performed using phase-specific segmentations for aortic root and ascending aorta. TTP for all parameters was compared to TTP of flow rate using paired t-tests. Time-averaged and peak values were assessed using Pearson correlation coefficient. P < 0.05 was considered statistically significant.Results: In the combined group, velocity in static vs. phase-specific segmentations differed by 0.8 cm/sec for the aortic root, and 0.1 cm/sec (P = 0.214) for the ascending aorta. Vorticity differed by 167 sec(-1) mL(-1) (P = 0.468) for the aortic root, and by 59 sec(-1) mL(-1) (P = 0.481) for the ascending aorta. Vorticity, helicity, and energy loss in the ascending aorta, aortic arch, and descending aorta peaked significantly later than flow rate. Time-averaged velocity and vorticity values correlated significantly in all segments.Data Conclusion: Static 4D flow MRI segmentation yields comparable results as multiphase segmentation for flow-related parameters, eliminating the need for time-consuming multiple segmentations. However, multiphase quantification is necessary for assessing peak values of aortic flow-related parameters. Show less
Juffermans, J.F.; Assen, H.C. van; Kiefte, B.J.C. te; Ramaekers, M.J.F.G.; Palen, R.L.F. van der; Boogaard, P. van den; ... ; Westenberg, J.J.M. 2022
(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm ... Show more(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 +/- 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16-30% and ICC = 0.84-0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3-26% and ICC = 0.87-1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3-10% and ICC = 0.96-1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients. Show less
Objectives Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than... Show moreObjectives Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood. Materials and Methods A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle. Results Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments. Conclusions Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation. Show less
Background Cardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However... Show moreBackground Cardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs. Methods A total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred. Results The mean growth rate in our population was 0.2 +/- 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 +/- 0.5 vs 0.2 +/- 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40-49 mm in diameter and yearly imaging of those measuring 50-54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%. Conclusions In our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach. Show less
Vargas, C.S.; Bauwens, M.; Pooters, I.N.A.; Pomme, S.; Peters, S.M.B.; Segbers, M.; ... ; Wierts, R. 2020
BackgroundPersonalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and... Show moreBackgroundPersonalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: Tc-99m, In-111, I-123, I-124, I-131, Lu-177, and Y-90.MethodsIn total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: I-131/I-123, I-131/I-124, Lu-177/In-111, Y-90/Tc-99m, and Y-90/In-111.ResultsFor Tc-99m, I-131, and Lu-177, a small minority of measurements were not within 5% range from the reference activity (percentage of measurements not within range: Tc-99m, 6%; I-131, 14%; Lu-177, 24%) and almost none were outside +/- 10% range. However, for In-111, I-123, I-124, and Y-90, more than half of all measurements were not accurate within +/- 5% range (In-111, 51%; I-123, 83%; I-124, 63%; Y-90, 61%) and not all were within +/- 10% margin (In-111, 22%; I-123, 35%; I-124, 15%; Y-90, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > +/- 10%) for the investigated theragnostic pairs, in particular for Y-90/In-111, I-131/I-123, and Y-90/Tc-99m.Conclusions Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry. Show less
Objective Guidelines on safe use of iodinated contrast material recommend intravenous prophylactic hydration to prevent post-contrast adverse (renal) effects. Recently, guidelines have been updated... Show moreObjective Guidelines on safe use of iodinated contrast material recommend intravenous prophylactic hydration to prevent post-contrast adverse (renal) effects. Recently, guidelines have been updated and standard prophylaxis is no longer recommended for the majority of patients. The current study aims to evaluate the consequences for clinical practice of the updated guidelines in terms of complications, hospitalisations, and costs. Methods The Contrast-Induced Nephropathy After Reduction of the prophylaxis Threshold (CINART) project is a retrospective observational study. All elective procedures with intravascular iodinated contrast administration at Maastricht University Medical Centre (UMC+) in patients aged > 18 years, formerly eligible for prophylaxis (eGFR 30-44 ml/min/1.73 m(2) or eGFR 45-59 ml/min/1.73 m(2) in combination with diabetes or > 1 predefined risk factor), and currently eligible for prophylaxis (eGFR < 30 ml/min/1.73 m(2)) were included. Data were used to calculate relative reductions in complications, hospitalisations, and costs associated with standard prophylactic intravenous hydration. CINART is registered with : NCT03227835. Results Between July 1, 2017, and July 1, 2018, 1992 elective procedures with intravascular iodinated contrast in patients formerly and currently eligible for prophylaxis were identified: 1808 in patients formerly eligible for prophylaxis and 184 in patients currently eligible for prophylaxis. At Maastricht UMC+, guideline updates led to large relative reductions in numbers of complications of prophylaxis (e.g. symptomatic heart failure; - 89%), extra hospitalisations (- 93%), and costs (- 91%). Conclusion Guideline updates have had a demonstrable impact on daily clinical practice benefiting patient, hospital, and health care budgets. Clinical practice varies between institutions and countries; therefore, a local estimation model is provided with which local impact on costs, hospitalisations, and complications can be calculated. Show less
Acute aortic syndromes comprise a group of potentially fatal conditions that result from weakening of the aortic vessel wall. Pre-emptive surgical intervention is currently reserved for patients... Show moreAcute aortic syndromes comprise a group of potentially fatal conditions that result from weakening of the aortic vessel wall. Pre-emptive surgical intervention is currently reserved for patients with severe aortic dilatation, although abundant evidence describes the occurrence of dissection and rupture in aortas with diameters below surgical thresholds. Modern imaging techniques (such as hybrid PET-CT and 4D flow MRI) afford the non-invasive assessment of anatomic, hemodynamic, and molecular features of the aorta, and may provide for a more accurate selection of patients who will benefit from preventative surgical intervention. In the current review, we summarize evidence and considerations regarding predictive aortic imaging and highlight evolving imaging modalities that have shown promise to improve risk assessment for the occurrence of dissection and rupture.Key PointsGuidelines for the preventative management of aortic disease depend on maximal vessel diameters, while these have shown to be poor predictors for the occurrence of catastrophic acute aortic events.Evolving imaging modalities (such as 4D flow MRI and hybrid PET-CT) afford a more comprehensive insight into anatomic, hemodynamic, and molecular features of the aorta and have shown promise to detect vessel wall instability at an early stage. Show less
Background The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (V-peak), mean pressure gradient (P-mean), and... Show moreBackground The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (V-peak), mean pressure gradient (P-mean), and aortic valve area (AVA) determine AS severity and play a pivotal role in the stratification towards valvular replacement. A multimodality imaging approach might be needed in cases of uncertainty about the actual severity of the stenosis. Purpose To compare four-dimensional phase-contrast magnetic resonance (4D PC-MR), two-dimensional (2D) PC-MR, and transthoracic echocardiography (TTE) for quantification of AS. Study Type Prospective. Population Twenty patients with various degrees of AS (69.3 +/- 5.0 years). Field Strength/Sequences 4D PC-MR and 2D PC-MR at 3T. Assessment We compared V-peak, P-mean, and AVA between TTE, 4D PC-MR, and 2D PC-MR. Flow eccentricity was quantified by means of normalized flow displacement, and its influence on the accuracy of TTE measurements was investigated. Statistical Tests Pearson's correlation, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. Results 4D PC-MR measured higher V-peak (r = 0.95, mean difference + 16.4 +/- 10.7%, P <0.001), and P-mean (r = 0.92, mean difference + 14.9 +/- 16.0%, P = 0.013), but a less critical AVA (r = 0.80, mean difference + 19.9 +/- 20.6%, P = 0.002) than TTE. In contrast, unidirectional 2D PC-MR substantially underestimated AS severity when compared with TTE. Differences in V-peak between 4D PC-MR and TTE showed to be strongly correlated with the eccentricity of the flow jet (r = 0.89, P <0.001). Use of 4D PC-MR improved the concordance between V-peak and AVA (from 0.68 to 0.87), and between PG(mean) and AVA (from 0.68 to 0.86). Data Conclusion 4D PC-MR improves the concordance between the different AS parameters and could serve as an additional imaging technique next to TTE. Future studies should address the potential value of 4D PC-MR in patients with discordant echocardiographic parameters. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. Show less
Background: Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training... Show moreBackground: Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods: Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 +/- 0.9 years, BMI: 29.9 +/- 0.01 kg/m(2)) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results: VO2max increased (from 27.1 +/- 1.5 to 30.1 +/- 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 +/- 1.9 to 10.3 +/- 2.0 mu mol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 +/- 2.0 to 55.6 +/- 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 +/- 0.22% to 0.95 +/- 0.21%, p = 0.15). Conclusions: Twelve weeks of progressive endurance/strength training was effective in improving VO(2)max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function. Show less
Objective: To investigate the natural course of carotid plaque progression in transient ischemic attack/stroke patients by using serial multisequence magnetic resonance imaging (MRI). Materials and... Show moreObjective: To investigate the natural course of carotid plaque progression in transient ischemic attack/stroke patients by using serial multisequence magnetic resonance imaging (MRI). Materials and Methods: Forty transient ischemic attack/stroke patients with ipsilateral <70% carotid stenosis underwent MRI of the plaque ipsilateral to the symptomatic side at baseline and after 1 year. The MRI protocol consisted of T1-weighted turbo field-echo, time-of-flight, T2-weighted turbo spin-echo (TSE), and pre- and postgadopentetate dimeglumine-enhanced T1-weighted TSE images. For each plaque, carotid lumen volume, wall volume, total vessel volume (=carotid lumen volume + wall volume), the presence of a lipid-rich necrotic core (LRNC), fibrous cap (FC) status, and the presence of intraplaque hemorrhage (IPH) were assessed at both time points. Results: Over a 1-year period, mean carotid lumen volume decreased with 4.8% +/- 2.0% (+/- standard error) (P = 0.013). Mean wall volume increased with 11.2% +/- 2.2% (P < 0.001). Total vessel volume did not significantly change (P = 0.147). At baseline, there were 18 plaques with a LRNC, which also had a LRNC at 1-year follow-up. No plaque without a LRNC at baseline developed a LRNC during the follow-up period. All plaques with a LRNC had a thin and/or ruptured FC at both time points. Twelve patients had IPH both at baseline and at follow-up. In one patient, IPH disappeared, whereas in another patient, new IPH appeared at follow-up. The presence of IPH and a LRNC with a thin and/or ruptured FC were not significantly associated with plaque progression (P > 0.05). Conclusions: In symptomatic patients with an ipsilateral carotid plaque causing <70% stenosis, we found evidence for inward plaque remodeling over a 1-year period. Overall, the presence/absence of IPH, a LRNC, and FC status did not change over 1 year. Show less
OBJECTIVE:: To investigate the natural course of carotid plaque progression in transient ischemic attack/stroke patients by using serial multisequence magnetic resonance imaging (MRI). MATERIALS... Show moreOBJECTIVE:: To investigate the natural course of carotid plaque progression in transient ischemic attack/stroke patients by using serial multisequence magnetic resonance imaging (MRI). MATERIALS AND METHODS:: Forty transient ischemic attack/stroke patients with ipsilateral <70% carotid stenosis underwent MRI of the plaque ipsilateral to the symptomatic side at baseline and after 1 year. The MRI protocol consisted of T1-weighted turbo field-echo, time-of-flight, T2-weighted turbo spin-echo (TSE), and pre- and postgadopentetate dimeglumine-enhanced T1-weighted TSE images. For each plaque, carotid lumen volume, wall volume, total vessel volume (=carotid lumen volume + wall volume), the presence of a lipid-rich necrotic core (LRNC), fibrous cap (FC) status, and the presence of intraplaque hemorrhage (IPH) were assessed at both time points. RESULTS:: Over a 1-year period, mean carotid lumen volume decreased with 4.8% ± 2.0% (±standard error) (P = 0.013). Mean wall volume increased with 11.2% ± 2.2% (P < 0.001). Total vessel volume did not significantly change (P = 0.147). At baseline, there were 18 plaques with a LRNC, which also had a LRNC at 1-year follow-up. No plaque without a LRNC at baseline developed a LRNC during the follow-up period. All plaques with a LRNC had a thin and/or ruptured FC at both time points. Twelve patients had IPH both at baseline and at follow-up. In one patient, IPH disappeared, whereas in another patient, new IPH appeared at follow-up. The presence of IPH and a LRNC with a thin and/or ruptured FC were not significantly associated with plaque progression (P > 0.05). CONCLUSIONS:: In symptomatic patients with an ipsilateral carotid plaque causing <70% stenosis, we found evidence for inward plaque remodeling over a 1-year period. Overall, the presence/absence of IPH, a LRNC, and FC status did not change over 1 year. Show less
Schrauwen-Hinderling, V.B.; Hesselink, M.K.C.; Meex, R.; Made, S. van der; Schar, M.; Lamb, H.; ... ; Schrauwen, P. 2010
Context: Skeletal muscle and cardiac lipid accumulation are associated with diminished insulin sensitivity and cardiac function, respectively. In skeletal muscle, physical activity paradoxically... Show moreContext: Skeletal muscle and cardiac lipid accumulation are associated with diminished insulin sensitivity and cardiac function, respectively. In skeletal muscle, physical activity paradoxically increases fat accumulation, despite improvement in insulin sensitivity. Whether cardiac muscle responds similarly remains unknown. Objective: The objective of the study was to investigate cardiac lipid content and cardiac function after a 12-wk training program. Design: This was an intervention study with pre/postmeasurements. Setting: The study was conducted at Maastricht University Medical Center. Participants: Participants included 14 healthy, male overweight/obese subjects (age 58.4 +/- 0.9 yr, body mass index 29.9 +/- 0.01 kg/m(2)). Intervention: Intervention included a supervised 12-wk training program with three sessions per week (endurance and strength training). Main Outcome Measures: Maximal whole-body oxygen uptake, fasting plasma parameters, systolic function (by CINE-magnetic resonance imaging), and cardiac lipid content (by proton magnetic resonance spectroscopy) were measured. Results: Maximal whole-body oxygen uptake increased (from 2559 +/- 131 to 2702 +/- 124 ml/min after training, P = 0.05). Plasma concentrations of glucose decreased (from 6.3 +/- 0.2 to 5.7 +/- 0.2 mmol/liter, P < 0.001); plasma triacylglycerols and (free) fatty acids did not change. Also, body weight (from 94.2 +/- 3.6 to 92.9 +/- 3.6 kg, P = 0.10) and fat percentage (from 33.6 +/- 1.7 to 32.5 +/- 2.0%, P = 0.14) was unchanged. Left ventricular ejection fraction improved (from 52.2 +/- 1.3 to 54.2 +/- 1.2%, P = 0.02), and cardiac lipid content in the septum was decreased after training (0.99 +/- 0.15 to 0.54 +/- 0.04%, P = 0.02). Conclusions: Twelve weeks of endurance/strength training significantly reduced cardiac lipid content in overweight subjects and was paralleled by improved ejection fraction. This is in line with a lipotoxic action of (excess) cardiac lipids on cardiac function, although a causal relationship cannot be derived from this study. Further research is needed to clarify the clinical relevance of cardiac lipid content in the etiology of cardiovascular complications. (J Clin Endocrinol Metab 95: 1932-1938, 2010) Show less