Saskia G. C. van Elderen

Association between diffuse myocardial fibrosis by cardiac magnetic resonance contrast-enhanced T(1) mapping and subclinical myocardial dysfunction in diabetic patients: a pilot study.

Background— Diabetic patients have increased interstitial myocardial fibrosis on histological examination. Magnetic resonance imaging (MRI) T1 mapping is a previously validated imaging technique that can quantify the burden of global and regional interstitial fibrosis. However, the association between MRI T1 mapping and subtle left ventricular (LV) dysfunction in diabetic patients is unknown. Methods and Results— Fifty diabetic patients with normal LV ejection fraction (EF) and no underlying coronary artery disease or regional macroscopic scar on MRI delayed enhancement were prospectively recruited. Diabetic patients were compared with 19 healthy controls who were frequency matched in age, sex and body mass index. There were no significant differences in mean LV end-diastolic volume index, end-systolic volume index and LVEF between diabetic patients and healthy controls. Diabetic patients had significantly shorter global contrast-enhanced myocardial T1 time (425±72 ms vs. 504±34 ms, P<0.001). There was no correlation between global contrast-enhanced myocardial T1 time and LVEF (r=0.14, P=0.32) in the diabetic patients. However, there was good correlation between global contrast-enhanced myocardial T1 time and global longitudinal strain (r=−0.73, P<0.001). Global contrast-enhanced myocardial T1 time was the strongest independent determinant of global longitudinal strain on multivariate analysis (standardized &bgr;=−0.626, P<0.001). Similarly, there was good correlation between global contrast-enhanced myocardial T1 time and septal E′ (r=0.54, P<0.001). Global contrast-enhanced myocardial T1 time was also the strongest independent determinant of septal E′ (standardized &bgr;=0.432, P<0.001). Conclusions— A shorter global contrast-enhanced myocardial T1 time was associated with more impaired longitudinal myocardial systolic and diastolic function in diabetic patients.

Association of Aortic Arch Pulse Wave Velocity with Left Ventricular Mass and Lacunar Brain Infarcts in Hypertensive Patients: Assessment with MR Imaging

PURPOSE To assess the possible association between aortic arch stiffness, which may cause hypertensive cardiovascular disease, and cardiac and cerebral end-organ damage in patients with hypertension by using magnetic resonance (MR) imaging. MATERIALS AND METHODS Approval from the local institutional review board was obtained, and patients gave informed consent. Fifty patients with hypertension (31 women and 19 men; mean age +/- standard deviation, 49.2 years +/- 12.7; mean systolic blood pressure, 152.1 mm Hg +/- 22.3; mean diastolic blood pressure, 88.0 mm Hg +/- 13.1), compliant for treatment with antihypertensive medication, were prospectively enrolled for MR examinations of the aorta, heart, and brain with standard pulse sequences. Aortic arch pulse wave velocity (PWV), left ventricular (LV) mass, LV systolic and diastolic function, lacunar brain infarcts, and periventricular and deep white matter hyperintensities (WMHs) were assessed. Univariable and multiple linear and logistic regression analyses were used for statistical analyses. RESULTS Mean aortic arch PWV was 7.3 m/sec +/- 2.5. Aortic arch PWV was statistically significantly associated with LV mass (r = 0.30, P = .03, beta = 1.73); indexes of systolic function, including ejection fraction (r = -0.38, P = .01, beta = -1.12); indexes of diastolic function, including the ratio of early diastolic to atrial contraction peak filling rates (r = -0.44, P < .01, beta = -0.11); lacunar brain infarcts (odds ratio [OR] = 1.8, P < .01); and periventricular (OR = 1.5, P = .01) and deep (OR = 1.6, P = .01) WMHs. Aortic arch PWV was statistically significantly associated with LV mass (r = 0.37, P = .03, beta = 2.11) and lacunar brain infarcts (OR = 1.8, P = .04), independent of age, sex, and hypertension duration, but not with indexes of diastolic and systolic function and WMHs. CONCLUSION Aortic arch stiffness is associated with LV mass and lacunar brain infarcts in hypertensive patients, independent of age, sex, and hypertension duration; these manifestations of end-organ damage may help to risk stratify hypertensive patients.

Cerebral Perfusion and Aortic Stiffness Are Independent Predictors of White Matter Brain Atrophy in Type 1 Diabetic Patients Assessed With Magnetic Resonance Imaging

OBJECTIVE To identify vascular mechanisms of brain atrophy in type 1 diabetes mellitus (DM) patients by investigating the relationship between brain volumes and cerebral perfusion and aortic stiffness using magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS Approval from the local institutional review board was obtained, and patients gave informed consent. Fifty-one type 1 DM patients (30 men; mean age 44 ± 11 years; mean DM duration 23 ± 12 years) and 34 age- and sex-matched healthy control subjects were prospectively enrolled. Exclusion criteria comprised hypertension, stroke, aortic disease, and standard MRI contraindications. White matter (WM) and gray matter (GM) brain volumes, total cerebral blood flow (tCBF), total brain perfusion, and aortic pulse wave velocity (PWV) were assessed using MRI. Multivariable linear regression analysis was used for statistics, with covariates age, sex, mean arterial pressure, BMI, smoking, heart rate, DM duration, and HbA1c. RESULTS Both WM and GM brain volumes were decreased in type 1 DM patients compared with control subjects (WM P = 0.04; respective GM P = 0.03). Total brain perfusion was increased in type 1 DM compared with control subjects (β = −0.219, P < 0.05). Total CBF and aortic PWV predicted WM brain volume (β = 0.352, P = 0.024 for tCBF; respective β = −0.458, P = 0.016 for aortic PWV) in type 1 DM. Age was the independent predictor of GM brain volume (β = −0.695, P < 0.001). CONCLUSIONS Type 1 DM patients without hypertension showed WM and GM volume loss compared with control subjects concomitant with a relative increased brain perfusion. Total CBF and stiffness of the aorta independently predicted WM brain atrophy in type 1 DM. Only age predicted GM brain atrophy.

Increased Aortic Stiffness Measured by MRI in Patients With Type 1 Diabetes Mellitus and Relationship to Renal Function

OBJECTIVE Arterial stiffness is an important predictor of cardiovascular disease in type 1 diabetes mellitus (DM). The purpose of this study was to investigate whether type 1 DM is associated with increased aortic stiffness as measured by MRI, independently of renal dysfunction, and to evaluate the relationship between aortic stiffness and renal function within the normal range in patients with type 1 DM. MATERIALS AND METHODS We included 77 patients with type 1 DM (mean age, 46 ± 12 years) and 36 healthy control subjects matched for age and renal function in a cross-sectional study. Exclusion criteria consisted of microalbuminuria, renal impairment, aortic valve disease, and standard MRI contraindications. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, was assessed by MRI. Renal function was expressed as the estimated glomerular filtration rate (GFR). Mann-Whitney U test and Spearmans correlation analysis were performed. Stepwise multivariable logarithmic regressions with forward entry analysis for estimated GFR were performed to study the relationship with aortic PWV using interaction terms for type 1 DM. RESULTS Patients with type 1 DM without microalbuminuria or renal impairment show increased aortic PWV compared with control subjects (p < 0.05). There was a statistically significant correlation between estimated GFR and aortic PWV in patients with type 1 DM (p < 0.001; r = -0.427) and control subjects (p = 0.002; r = -0.502), with aortic PWV being increased in patients with type 1 DM for each given estimated GFR within the normal range (p < 0.001). The decrease in estimated GFR per increase in aortic PWV was similar for patients with type 1 DM and control subjects (p, not significant). CONCLUSION Our data show that aortic stiffness, as measured by MRI, is increased and inversely related to renal function in patients with type 1 DM with normal albuminuria and normal estimated GFR.

Abdominal visceral and subcutaneous fat increase, insulin resistance and hyperlipidemia in testicular cancer patients treated with cisplatin-based chemotherapy

Abstract Background. Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. Material and methods. We studied 19 testicular cancer patients (age 20–54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Results. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m2 (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Conclusion. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development of metabolic syndrome and CVD years later in individual testicular cancer survivors.

Associations between aortic pulse wave velocity and aortic and carotid vessel wall thickness in patients with hypertension: assessment with MRI

Hypertension puts continuous strain on arteries, resulting in arterial wall alterations such as vessel wall thickening and vessel wall stiffening. Due to the availability of suitable acoustic windows, vessel wall thickness (VWT) is studied traditionally by ultrasound from intima-media thickness in the carotid arteries. Arterial vessel wall stiffness can be expressed by Pulse Wave Velocity (PWV), the propagation speed of the systolic wave front through the aorta. For studying direct associations between PWV and VWT, it is desired to sample VWT in the aorta.

Unfavorable metabolic changes are accompanied by impaired myocardial function shortly after chemotherapy

Background Cardiovascular morbidity is a well known late complication of chemotherapy, for example for treatment of testicular cancer. In addition, development of a combination of overweight, hypertension and abnormal lipid profiles has been observed in these patients suggesting increased risk of developing the metabolic syndrome and diabetes. The early effects of chemotherapy on myocardial function and metabolic profile are largely unknown. Therefore, the purpose of this study was to assess short-term effects of chemotherapy in testicular cancer on myocardial function in relationship with alterations in metabolic profile. Methods Fourteen patients with testicular cancer were treated with bleomycin, etoposide and cisplatin. Before and after chemotherapy, magnetic resonance imaging techniques were used to assess cardiac systolic and diastolic function, and abdominal fat volume (summation of 3 slices at the level of the L5 vertebra). In addition, hepatic and myocardial triglyceride content were assessed using MR spectroscopy. Blood samples were taken at both occasions to obtain plasma lipid profile and to estimate insulin sensitivity. Results After chemotherapy, an unfavorable shift in metabolic profile was observed: Visceral abdominal fat volume was increased significantly (from186 ± 125 ml to 227 ± 162 ml. P< 0.05) without significant changes in BMI. Hepatic triglyceride content increased, although non-significant

Changes in body fat and lipid metabolism in testicular cancer patients undergoing curative chemotherapy.

337 Background: Testicular cancer (TC) survivors are at increased risk to develop metabolic syndrome and cardiovascular disease. We assessed the utility of proton magnetic resonance spectroscopy (H1-MRS) and aortic Pulse Wave Velocity (aoPWV) with MRI to detect the early effects of chemotherapy-induced changes in lipid metabolism on liver fat storage and vascular function in testicular cancer patients undergoing curative treatment. METHODS Nineteen 19 chemo-naïve TC patients (age 20-54 years) were studied before, shortly after (<3 months), and 9 months after the start of three or four cycles of cisplatin-based chemotherapy. At each visit, fasting blood samples for serum glucose, insulin, HbA1c, and lipids were collected, and abdominal subcutaneous (scFat) and visceral fat (visFat) volume, hepatic triglyceride content (HTgC), and aoPWV were assessed by MRI. All measurements were performed using validated methodology. Data were analysed using RM-ANOVA. RESULTS Shorty after cessation of chemotherapy there was an increase in fasting serum insulin (5.7±4.4 vs. 9.6±6.3; p=0.05), HOMA-index (1.3± 0.3 vs. 2.3± 0.4; p=0.006), HbA1c (5.2±0.3 vs. 5.3±0.6; p=0.03), total cholesterol (4.88±1.31 vs. 5.61±1.50; p=0.002) and LDL-cholesterol (3.31±1.16 vs. 3.73±1.41; p=0.02). This coincided with relative volume increases of scFAT (6.9%; 95%CI 0.4-13.4%) and visFAT (18.7%; 95%CI 2.4-35.1%), a unsignificant increase in HTgC (47.4%; 95%CI -5.4-129.5%). AoPWV did not change (0.2%; 95%CI -0.5-0.8%). All parameters that were increased at 3 months returned to baseline at 9 months, but the increases in scFAT and visFAT remained. CONCLUSIONS Cisplatinum-based chemotherapy in TC patients is associated with disturbances of glucose and lipid metabolism shortly after therapy but returns to baseline later. These changes did not translate into significant increases in HTgC and aoPWV, suggesting that these measures are of limited value to detect early chemotherapy-induced changes. Interestingly, scFAT and visFAT showed sustained increases, and this may explain the observed higher incidence in metabolic syndrome and (ensuing) cardiovascular disease in chemotherapy-treated TC patients.

Navigator techniques for coronary MRA at 7 T

Introduction Performance of the respiratory navigator is critical in coronary magnetic resonance angiography (MRA). At 7 T, the performance of a conventional 2D-selective navigator is adversely affected by field inhomogeneities and limited volumetric coverage of transmit/receive surface coils which must be used on systems without transmit array capability. Therefore, two navigator approaches, a 2Dselective navigator optimized for 7 T and a non-selective navigator that is less susceptible to field inhomogeneities, were implemented. Coronary MRAs were obtained with both techniques and quantitatively compared.