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Aims Duchenne muscular dystrophy (DMD) is an X‐linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 and usually die in the second to third decades of life from cardiac and respiratory failure. Symptomatic treatment includes the use of anti‐inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, and increased risk of cardiovascular disease. Novel treatment options include blockade of the renin–angiotensin–aldosterone system, because angiotensin as well as aldosterone contribute to persistent inflammation and fibrosis, and aldosterone blockade represents an efficacious anti‐fibrotic approach in cardiac failure. Recent preclinical findings enabled successful clinical testing of a combination of steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on dystrophic skeletal muscle and heart has not been investigated. Here, we tested efficacy of the novel non‐steroidal MRA finerenone as a monotherapy in a preclinical DMD model. Methods and results The dystrophin‐deficient, utrophin haploinsufficient mouse model of DMD was treated with finerenone and compared with untreated dystrophic and wild‐type controls. Grip strength, electrocardiography, cardiac magnetic resonance imaging, muscle force measurements, histological quantification, and gene expression studies were performed. Finerenone treatment alone resulted in significant improvements in clinically relevant functional parameters in both skeletal muscle and heart. Normalized grip strength in rested dystrophic mice treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued finerenone‐treated dystrophic mice showed an even greater relative improvement (P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD measured during a contraction‐induced injury protocol. Normalized limb muscle force after five lengthening contractions resulted in retention of 71 ± 7% of baseline force in finerenone‐treated compared with only 51 ± 4% in untreated dystrophic mice. Finerenone treatment also prevented significant reductions in myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. Moreover, treatment with finerenone led to very specific cardiac gene expression changes in clock genes that might modify cardiac pathophysiology in this DMD model. Conclusions Finerenone administered as a monotherapy is disease modifying for both skeletal muscle and heart in a preclinical DMD model. These findings support further evaluation of finerenone in DMD clinical trials.

BACKGROUND: The current standard method to measure intracardiac oxygen (O(2)) saturation is by invasive catheterization. Accurate noninvasive blood O(2) saturation by MRI could potentially reduce the duration and risk of invasive diagnostic procedures. PURPOSE: To noninvasively determine blood oxygen saturation in the heart with MRI and compare the accuracy with catheter measurements. STUDY TYPE: Prospective. SUBJECTS: Thirty-two patients referred for right heart catheterization (RHC) and five healthy subjects. FIELD STRENGTH/SEQUENCE: T2-prepared single-shot balanced steady-state free-precession at 1.5T. ASSESSMENT: MR signals in venous and arterial blood, hematocrit, and arterial O(2) saturation from a pulse oximeter were jointly processed to fit the Luz–Meiboom model and estimate blood O(2) saturation in the right heart. Interstudy reproducibility was evaluated in volunteers and patients. Interobserver reproducibility among three readers was assessed using data from volunteers and 10 patients. Accuracy of MR oximetry was compared to RHC in all patients. STATISTICAL TESTS: Coefficient of variation, intraclass correlation coefficient, Bland–Altman analysis, Pearson’s correlation. RESULTS: The coefficient of variation for interstudy reproducibility of O(2) saturation was 2.6% on average in volunteers and 3.2% in patients. Interobserver reproducibility among three observers yielded intraclass correlation coefficients of 0.81 and 0.87 respectively for RV and MPA O(2) saturation. O(2) saturation (y = 0.85x + 0.13, R = 0.78) and (a-v)O(2) difference (y = 0.71x + 0.90, R = 0.69) by MR and RHC were significantly correlated (N = 32, P < 0.05 in both cases) in patients. MR slightly overestimated O(2) saturation compared to RHC with 2% ± 5% bias and limits of agreement between −7% and 12%. DATA CONCLUSION: MR oximetry is repeatable and reproducible. Good agreement was shown between MR and catheter venous O(2) saturation and (a-v)O(2) difference in a cohort whose venous O(2) ranged from abnormally low to high levels, with most values in the normal physiological range. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Obesity is a strong risk factor for developing endometrial cancer and cardiovascular disease (CVD); consequently, understanding CVD mortality among endometrial cancer survivors is important. We analyzed Surveillance, Epidemiology and End Results Program data for 157,496 endometrial cancer cases diagnosed between 1988 and 2012. We calculated standardized mortality ratios (SMRs) for CVD and all-cause mortality comparing endometrial cancer cases and general population women. We categorized women into one of three prognostic groups (excellent, intermediate and poor) based on tumor characteristics. Cumulative incidence function curves were plotted to visualize absolute mortality risk in the presence of competing risks. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression for cause-specific mortality. Deaths were as follows: endometrial cancer 40.6%, CVD 20.5%, other cancers 18.7% and other causes 20.3%. Women with endometrial cancer were more likely to die from CVD (age-adjusted SMR = 8.8, 95% CI = 8.7-9.0) and all causes (age-adjusted SMR = 15.9, 95% CI = 15.8-16.0) compared to general population women. In case-only analyses, higher CVD mortality was associated with older age, Black ethnicity and lack of surgical treatment. Poor prognosis cancers (non-endometrioid histology and late stage) were related to higher mortality from each cause, with the highest HRs observed for endometrial cancer-specific mortality. Among women diagnosed with excellent prognosis tumors (endometrioid, well-differentiated and early stage), absolute risk of CVD mortality surpassed endometrial cancer-specific mortality 5 years after diagnosis. Women diagnosed with common forms of endometrial cancer have a high CVD burden. After diagnosis, cardiovascular health should be emphasized for these women to reduce mortality.

MRI provides a non-invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T1, T2 and T2*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T1, T2 and T2* maps, we posited that an integrated treadmill exercise-quantitative relaxometry paradigm can rapidly characterize exercise-induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T1, T2 and T2* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post-exercise. Our results show that T1, T2 and T2* are significantly and differentially increased immediately post-exercise among the leg muscle groups, and these values recover to near baseline within 30-44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender.

Purpose To compare exercise stress cardiac magnetic resonance (cardiac MR) to echocardiography in healthy volunteers with respect to adequacy of endocardial visualization and confidence of stress study interpretation.

Purpose To describe and characterize a new approach to first-pass myocardial perfusion utilizing balanced steady-state free precession acquisition without the use of saturation recovery or other magnetization preparation. Theory The balanced steady-state free precession sequence is inherently sensitive to contrast agent enhancement of the myocardium. This sensitivity can be used to advantage in first-pass myocardial perfusion imaging by eliminating the need for magnetization preparation. Methods Bloch equation simulations, phantom experiments, and in vivo 2D imaging studies were run comparing the proposed technique with three other methods: saturation recovery spoiled gradient echo, saturation recovery steady-state free precession, and steady-state spoiled gradient echo without magnetization preparation. Additionally, an acquisition-reconstruction strategy for 3D perfusion imaging is proposed and initial experience with this approach is demonstrated in healthy subjects and one patient. Results Phantom experiments verified simulation results showing the sensitivity of the balanced steady-state free precession sequence to contrast agent enhancement in solid tissue is similar to that of magnetization-prepared acquisitions. Images acquired in normal volunteers showed the proposed technique provided superior signal and signal-to-noise ratio compared with all other sequences at baseline as well as postcontrast. Conclusions A new approach to first-pass myocardial perfusion is presented that obviates the need for magnetization preparation and provides high signal-to-noise ratio. Magn Reson Med 71:133–144, 2014. © 2013 Wiley Periodicals, Inc.

To reduce study start-up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders and Stroke embarked on an initiative to create common data elements for neuroscience clinical research. The Common Data Element Team developed general common data elements, which are commonly collected in clinical studies regardless of therapeutic area, such as demographics. In the present project, we applied such approaches to data collection in Friedreich's ataxia (FRDA), a neurological disorder that involves multiple organ systems. To develop FRDA common data elements, FRDA experts formed a working group and subgroups to define elements in the following: ataxia and performance measures; biomarkers; cardiac and other clinical outcomes; and demographics, laboratory tests, and medical history. The basic development process included identification of international experts in FRDA clinical research, meeting by teleconference to develop a draft of standardized common data elements recommendations, vetting of recommendations across the subgroups, and dissemination of recommendations to the research community for public comment. The full recommendations were published online in September 2011 at http://www.commondataelements.ninds.nih.gov/FA.aspx. The subgroups' recommendations are classified as core, supplemental, or exploratory. Template case report forms were created for many of the core tests. The present set of data elements should ideally lead to decreased initiation time for clinical research studies and greater ability to compare and analyze data across studies. Their incorporation into new, ongoing studies will be assessed in an ongoing fashion to define their utility in FRDA.

This study was performed to determine the relative role of cardiac magnetic resonance (CMR) imaging and endomyocardial biopsy (EMB) in the evaluation of cardiomyopathy. Sixty-six patients with a clinical diagnosis of nonischemic dilated cardiomyopathy or restrictive cardiomyopathy underwent both EMB and CMR imaging as part of their diagnostic evaluation. The authors retrospectively reviewed the results of these two methods to determine their diagnostic impact and congruency. CMR imaging provided data on cardiac anatomy, left ventricular volumes, mass, and function in 85% of the patients, uncovered fibrosis in 31%, myocardial ischemia in 7%, and fibrofatty infiltration in two patients. EMB provided the histologic findings of cardiomyocyte hypertrophy in 77% of patients and substantial interstitial fibrosis in 59%. Six patients had EMB-proven amyloid heart disease, which was detected by CMR imaging in two. CMR imaging showed patterns of late gadolinium enhancement supportive of infiltrative disease or inflammation in 6 patients with EMB-proven definite (n=3) or borderline (n=3) myocarditis, but failed to do so in two other patients with borderline and two with resolving myocarditis. At the present time, CMR imaging and EMB remain complementary procedures in the evaluation of cardiomyopathic conditions.

Quantitative T₂ mapping was recently shown to be superior to T₂-weighted imaging in detecting T₂ changes across myocardium. Pixel-wise T₂ mapping is sensitive to misregistration between the images used to generate the parameter map. In this study, utility of two motion-compensation strategies-(i) navigator gating with prospective slice correction and (ii) nonrigid registration-was investigated for myocardial T₂ mapping in short axis and horizontal long axis views. Navigator gating provides respiratory motion compensation, whereas registration corrects for residual cardiac and respiratory motion between images; thus, the two strategies provided complementary functions. When these were combined, respiratory-motion-induced T₂ variability, as measured by both standard deviation and interquartile range, was comparable to that in breath-hold T₂ maps. In normal subjects, this combined motion-compensation strategy increased the percentage of myocardium with T₂ measured to be within normal range from 60.1% to 92.2% in short axis and 62.3% to 92.7% in horizontal long axis. The new motion-compensated T₂ mapping technique, which combines navigator gating, prospective slice correction, and nonrigid registration to provide through-plane and in-plane motion correction, enables a method for fully automatic and robust free-breathing T₂ mapping.

This article describes an MR-safe treadmill that enables cardiovascular exercise stress testing adjacent to the MRI system, facilitating cardiac MR imaging immediately following exercise stress. The treadmill was constructed of nonferromagnetic components utilizing a hydraulic power system. Computer control ensured precise execution of the standard Bruce treadmill protocol commonly used for cardiovascular exercise stress testing. The treadmill demonstrated no evidence of ferromagnetic attraction and did not affect image quality. Treadmill performance met design specifications both inside and outside the MRI environment. Ten healthy volunteers performed the Bruce protocol with the treadmill positioned adjacent to the MRI table. Upon reaching peak stress (98 ± 8% of age-predicted maximum heart rate), the subjects lay down directly on the MRI table, a cardiac array coil was placed, an intravenous line connected, and stress cine and perfusion imaging performed. Cine imaging commenced on average within 24 ± 4 s and was completed within 40 ± 7 s of the end of exercise. Subject heart rates were 86 ± 9% of age-predicted maximum heart rate at the start of imaging and 81 ± 9% of age-predicted maximum heart rate upon completion of cine imaging. The MRI-compatible treadmill was shown to operate safely and effectively in the MRI environment.

Although the electrocardiogram is known to be nondiagnostic within the bore of any high-field magnet due to the magnetohydrodynamic effect, there are an increasing number of applications that require accurate electrocardiogram monitoring of a patient inside the MRI room but outside of the magnet bore. Magnetohydrodynamic effects on the ST segment of the electrocardiogram waveform were investigated in six subjects at magnetic field strengths ranging from 6.4 mT to 652 mT at the aortic midarch, and the electrocardiogram was found to be accurate at magnetic fields below 70 mT. This corresponds to a distance of 160 cm from the isocenter and 80 cm from the bore entrance for the 1.5-T MRI system used in this study. These results can be translated to any MRI system, with knowledge of the fringe field. Accurate electrocardiogram monitoring is feasible in close proximity to the MRI magnet, such as during and after pharmacologic or exercise stress, or interventional or surgical procedures performed in the MRI room.

Background Women consistently have poorer revascularization outcomes and more coronary vascular complications compared to men. This has been attributed to smaller coronary arteries, though limited data exist to support this assumption. Hypothesis By using volumetric data obtained from multidetector cardiovascular computed tomography (CCT), we sought to determine to what extent gender influences coronary artery dimensions and test the hypothesis that women would have smaller coronary dimensions even after normalizing for body surface area and cardiac mass. Methods CCT examinations completed on a 64-slice scanner were identified from a university cardiovascular database. Data sets from 50 women and 44 men without coronary artery disease were selected for analysis. Cross-sectional areas of proximal and distal segments of the left anterior descending (LAD), circumflex (LCx), and right coronary artery (RCA) were measured, blinded to patient gender. Measurements were compared using 2-sample t tests and linear regression analysis techniques accounting for body surface area (BSA) and left ventricular (LV) mass. Results Analysis of cross-sectional coronary artery areas, unadjusted for BSA and LV mass showed smaller coronary artery size in women compared to men in the proximal portion of both the LAD (P = .01) and RCA (P = .002), but no significant difference in the remaining coronary segments. Conclusion Gender significantly impacts proximal LAD and RCA size. Differences in coronary artery dimensions may explain some, but not all excess gender-related risk with coronary artery revascularization, underscoring the importance of considering multiple contributing factors. Copyright © 2010 Wiley Periodicals, Inc.

Objective: To evaluate varying CT settings to visualize pediatric vascular stents in comparison to digital angiography (DA). Background: There is a great clinical interest in substituting noninvasive methods to follow up children with congenital heart disease after interventional treatment. Materials and Methods: CT studies in small children with transcatheter placed stents were reviewed, retrospectively. Furthermore, eight stents were implanted in tubes and partially obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with corresponding tube settings. The effects of dose on image quality were evaluated regarding stent size, strut thickness, and in-stent stenoses in comparison to DA. Results: Fourteen children with 28 implanted stents were identified. Significant differences between higher and lower radiation settings were not found, corresponding with the phantom, where moderate tube setting showed the best results. In vitro, there was an improvement with increasing number of detector rows, which resulted in a decrease of stent strut overestimation (295% down to 201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to 91%; P = 0.003) and moderate in-stent stenoses (80% up to 99%; P = 0.0001). Conclusion: Higher radiation exposure settings did not improve image quality, suggesting that the exams could be performed at a lower radiation dose. © 2008 Wiley-Liss, Inc.

Aneurysms of the coronary arteries are rare and are usually associated with atherosclerosis in adults. Mycotic coronary artery aneurysms are exceedingly uncommon and are typically associated with systemic bacteremia, endocarditis, or septic emboli. Literature and data describing the management of mycotic coronary artery aneurysms are limited. This case describes the successful diagnosis of a large right coronary artery aneurysm by transesophageal echocardiogram as well as the successful management of the aneurysm.

To reduce study start-up time, increase data sharing, and assist investigators conducting clinical studies, the National Institute of Neurological Disorders and Stroke embarked on an initiative to create common data elements for neuroscience clinical research. The Common Data Element Team developed general common data elements, which are commonly collected in clinical studies regardless of therapeutic area, such as demographics. In the present project, we applied such approaches to data collection in Friedreich's ataxia (FRDA), a neurological disorder that involves multiple organ systems. To develop FRDA common data elements, FRDA experts formed a working group and subgroups to define elements in the following: ataxia and performance measures; biomarkers; cardiac and other clinical outcomes; and demographics, laboratory tests, and medical history. The basic development process included identification of international experts in FRDA clinical research, meeting by teleconference to develop a draft of standardized common data elements recommendations, vetting of recommendations across the subgroups, and dissemination of recommendations to the research community for public comment. The full recommendations were published online in September 2011 at http://www.commondataelements.ninds.nih.gov/FA.aspx. The subgroups' recommendations are classified as core, supplemental, or exploratory. Template case report forms were created for many of the core tests. The present set of data elements should ideally lead to decreased initiation time for clinical research studies and greater ability to compare and analyze data across studies. Their incorporation into new, ongoing studies will be assessed in an ongoing fashion to define their utility in FRDA.