Quantification of aortic stenosis diagnostic parameters: comparison of fast 3 direction and 1 direction phase contrast CMR and transthoracic echocardiography.

BACKGROUND: Aortic stenosis (AS) is a common valvular disorder, and disease severity is currently assessed by transthoracic echocardiography (TTE). However, TTE results can be inconsistent in some patients, thus other diagnostic modalities such as cardiovascular magnetic resonance (CMR) are demanded. While traditional unidirectional phase-contrast CMR (1Dir PC-CMR) underestimates velocity if the imaging plane is misaligned to the flow direction, multi-directional acquisitions are expected to improve velocity measurement accuracy. Nonetheless, clinical use of multidirectional techniques has been hindered by long acquisition times. Our goal was to quantify flow parameters in patients using 1Dir PC-CMR and a faster multi-directional technique (3Dir PC-CMR), and compare to TTE. METHODS: Twenty-three patients were prospectively assessed with TTE and CMR. Slices above the aortic valve were acquired for both PC-CMR techniques and cine SSFP images were acquired to quantify left ventricular stroke volume. 3Dir PC-CMR implementation included a variable density sampling pattern with acceleration rate of 8 and a reconstruction method called ReVEAL, to significantly accelerate acquisition. 3Dir PC-CMR reconstruction was performed offline and ReVEAL-based image recovery was performed on the three (x, y, z) encoding pairs. 1Dir PC-CMR was acquired with GRAPPA acceleration rate of 2 and reconstructed online. CMR derived flow parameters and aortic valve area estimates were compared to TTE. RESULTS: ReVEAL based 3Dir PC-CMR derived parameters correlated better with TTE than 1Dir PC-CMR. Correlations ranged from 0.61 to 0.81 between TTE and 1Dir PC-CMR and from 0.61 to 0.87 between TTE and 3Dir-PC-CMR. The correlation coefficients between TTE, 1Dir and 3Dir PC-CMR Vpeakwere 0.81 and 0.87, respectively. In comparison to ReVEAL, TTE slightly underestimates peak velocities, which is not surprising as TTE is only sensitive to flow that is parallel to the acoustic beam. CONCLUSIONS: By exploiting structure unique to PC-CMR, ReVEAL enables multi-directional flow imaging in clinically feasible acquisition times. Results support the hypothesis that ReVEAL-based 3Dir PC-CMR provides better estimation of hemodynamic parameters in AS patients in comparison to 1Dir PC-CMR. While TTE can accurately measure velocity parallel to the acoustic beam, it is not sensitive to the other directions of flow. Therefore, multi-directional flow imaging, which encodes all three components of the velocity vector, can potentially outperform TTE in patients with eccentric or multiple jets.

Factors Determining Left Main Coronary Artery Luminal Area.

BACKGROUND: A certain minimal luminal cross-sectional area has been traditionally used in clinical practice as a cut-off value to determine severity of left main coronary artery (LMCA) stenosis. The severity of stenosis, however, depends on the baseline luminal area (ie, area prior to stenosis), which may vary among individuals. The present study was undertaken to define normal LMCA luminal area using current technology in vivo. METHODS: LMCA luminal area was determined using multislice computed tomography coronary angiography. Eighty-six subjects with normal coronary arteries and calcium score of zero were included in this study. Left ventricular (LV) mass and LV volumes (systolic, diastolic) were also measured. RESULTS: A wide distribution was found in LMCA luminal area, with median value 17.3 mm² and range 8.1-33.9 mm². A relationship was found between log(LMCA luminal area) and log(LV mass) (r=.515; P<.001) and with body surface area (r=.273; P=.01). Significant relationships were also found between LMCA luminal area and LV volumes (systolic, diastolic). In multiple regression analysis, however, the LV mass was the only independent predictor of LMCA luminal area. CONCLUSION: LMCA luminal area varies substantially among individuals with normal coronary arteries and is related to many other factors. The data suggest that the current practice of using a minimal luminal area cut-off when assessing LMCA stenosis may be misleading, and thus available information should be individualized.

Diagnostic Performance of Treadmill Exercise Cardiac Magnetic Resonance: The Prospective, Multicenter Exercise CMR's Accuracy for Cardiovascular Stress Testing (EXACT) Trial.

BACKGROUND: Stress cardiac magnetic resonance (CMR) has typically involved pharmacologic agents. Treadmill CMR has shown utility in single-center studies but has not undergone multicenter evaluation. METHODS AND RESULTS: Patients referred for treadmill stress nuclear imaging (SPECT) were prospectively enrolled across 4 centers. After rest (99m)Tc SPECT, patients underwent resting cine CMR. In-room stress was then performed using an MR-compatible treadmill with continuous 12-lead electrocardiogram monitoring. At peak stress, (99m)Tc was injected, and patients rapidly returned to the MR scanner isocenter for real-time, free-breathing stress cine and perfusion imaging. After recovery, cine and rest perfusion followed by late gadolinium enhancement acquisitions concluded CMR imaging. Stress SPECT was then acquired in adjacent nuclear laboratories. A subset of patients not referred for invasive coronary angiography within 2 weeks of stress underwent coronary computed tomography angiography. Angiographic data available in 94 patients showed sensitivity of 79%, specificity of 99% for exercise CMR with positive predictive value of 92% and negative predictive value of 96%. Agreement between treadmill stress CMR and angiography was strong (κ=0.82), and moderate between SPECT and angiography (κ=0.46) and CMR versus SPECT (κ=0.48). CONCLUSIONS: The multicenter EXACT trial indicates excellent diagnostic value of treadmill stress CMR in typical patients referred for exercise SPECT.

Detection of Intraneural Median Nerve Microvascularity Using Contrast-Enhanced Sonography: A Pilot Study.

OBJECTIVES: Demonstrating vascularity within the human median nerve may be difficult using power Doppler sonography. To this end, a pilot study documenting contrast-enhanced vascularity of the median nerve was conducted. METHODS: Patients undergoing contrast-enhanced transthoracic echocardiography were recruited for this study (n = 24). During echocardiography, a simultaneous contrast-enhanced sonographic examination of the median nerve was conducted. The study and study protocol were built from preclinical evidence. Image analysis was based on the power Doppler pixel intensity within a defined region of interest to obtain quantitative data representing the average pixel intensity, maximum pixel intensity, and power Doppler pixel dot count. Semiquantitative data representing the power Doppler dot count grading were also obtained. RESULTS: Spearman correlations between analytical methods showed strong positive, statistically significant (P< .05) correlations between the average pixel intensity and maximum pixel intensity and between the power Doppler dot count and dot count grading. Statistically significant increases in the average pixel intensity and power Doppler dot count were seen at all but 1 time point throughout the contrast-enhanced sonographic examination when compared to precontrast administration. Statistically significant increases in the maximum pixel intensity were seen at all but 4 time points. CONCLUSIONS: These pilot results represent early evidence that contrast-enhanced sonography can be used to image median nerve vascularity. In this convenience sample, median nerve contrast-enhanced sonographic data collection was feasible, safe, and consistent.

Collaborating with cardiac sonographers to develop work-related musculoskeletal disorder interventions.

For more than two decades, surveys of imaging technologists, including cardiac sonographers, diagnostic medical sonographers and vascular technologists, have consistently reported high prevalence of work-related musculoskeletal discomfort (WRMSD). Yet, intervention research involving sonographers is limited. In this study, we used a participatory approach to identifying needs and opportunities for developing interventions to reduce sonographers' exposures to WRMSD risk factors. In this paper, we present some of those needs. We include descriptions of two interventions, targeted for cardiac sonographers, that were developed, through an iterative process, into functional prototypes that were evaluated in pilot tests by practicing sonographers. One of these interventions is now in daily use. We would like other engineers and ergonomists to recognise this area of opportunity to apply their knowledge of biomechanics and design in order to begin to address the high prevalence of WRMSDs in sonographers, by working with sonographers to develop useful and usable interventions. Practitioner Summary: This paper discusses needs, opportunities and methods for working with sonographers in order to develop interventions to reduce their exposure to risk factors for work-related musculoskeletal discomfort. Results from field tests of two novel interventions targeting cardiac sonographers are also presented.

Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing.

STUDY OBJECTIVE: To compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing. DESIGN: Single-center retrospective cohort study. SETTING: Two outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson. PATIENTS: A total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between groups, except for chronic kidney disease (p<0.001), congestive heart failure (p=0.041), and mean age (p=0.004). The primary outcome was the occurrence of adverse effects-arrhythmia, chest pain or tightness, dizziness, dyspnea, flushing, or headache, and use of the rescue agent aminophylline-in the adenosine and regadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, p<0.001). The patients given regadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, p<0.001), dyspnea (66.0% vs 17.7%, p<0.001), and headache (25.1% vs 3.1%, p<0.001), and they had a significantly higher rate of aminophylline rescue use (19.2% vs 0.8%, p<0.001). A secondary objective evaluated the financial impact of each agent, and adenosine exhibited a medication price that was more than $100/patient lower than regadenoson based on the average wholesale price. CONCLUSION: Among patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson.

High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.

This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue.

A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (ß-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-ß, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.

Comparison of treadmill exercise stress cardiac MRI to stress echocardiography in healthy volunteers for adequacy of left ventricular endocardial wall visualization: A pilot study.

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. MATERIALS AND METHODS: Twenty-eight healthy volunteers (age 28 ± 11 years, 15 males) underwent exercise stress echo and cardiac MR one week apart assigned randomly to one test first. Stress cardiac MR was performed using an MRI-compatible treadmill; stress echo was performed as per routine protocol. Cardiac MR and echo images were independently reviewed and scored for adequacy of endocardial visualization and confidence in interpretation of the stress study. RESULTS: Heart rate at the time of imaging was similar between the studies. Average time from cessation of exercise to start of imaging (21 vs. 31 s, P < 0.001) and time to acquire stress images (20 vs. 51 s, P < 0.001) was shorter for cardiac MR. The number of myocardial segments adequately visualized was significantly higher by cardiac MR at rest (99.8% vs. 96.4%, P = 0.002) and stress (99.8% vs. 94.1%, P = 0.001). The proportion of subjects in whom there was high confidence in the interpretation was higher for cardiac MR than echo (96% vs. 60%, P = 0.005). CONCLUSION: Exercise stress cardiac MR to assess peak exercise wall motion is feasible and can be performed at least as rapidly as stress echo.

Two decades of Huntington disease testing: patient's demographics and reproductive choices.

Predictive testing for Huntington disease (HD) has been available in the United States (US) since 1987, and the Indiana University Predictive Testing Program has been providing this testing since 1990. To date there has been no published description of those who present for such testing in the US. Here we describe demographics of 141 individuals and reproductive decision making of a subset of 16 of those individuals who underwent predictive HD testing between 1990 and 2010 at one site in the US. This study is a retrospective chart review of the "Personal History Questionnaire" participants completed prior to testing. As seen in other studies, most participants were female (64.5 %), in their mid-30s (mean = 34), and had at least one child prior to testing (54 %). Multiple demographic datum points are described, and the reproductive decision making of these at-risk individuals was analyzed using Fisher's Exact Tests. Of those women who had children before learning of their risk to inherit HD, those who attended church more frequently, had three or more children total, or whose mother was affected with HD were more likely to be comfortable with their choice to have children. We conclude that these demographic factors influence the reproductive decision-making of individuals at risk for HD. Psychologists, clinical geneticists, and genetic counselors may be able to use this information to help counsel at-risk patients regarding current or past reproductive decision making.

Relationship of cardiac magnetic resonance imaging and myocardial biopsy in the evaluation of nonischemic cardiomyopathy.

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.

Isolated cardiac metastasis from plasmacytoid urothelial carcinoma of the bladder.

UNLABELLED: A 57-year-old male with a history of hypertension presented with shortness of breath, intermittent substernal chest pain, subjective fevers, and a 30-pound weight loss. He was found to have a bladder mass four months prior to presentation, for which he underwent cystoscopy and surgical removal. Pathology demonstrated high-grade superficial plasmacytoid urothelial carcinoma extending into the submucosa but not the muscularis propria. Given the superficial nature of his bladder cancer, a cystectomy was deferred. He was subsequently lost to follow-up care. On arrival, physical exam was notable for tachycardia, tachypnea, and distant heart sounds. An ECG showed an incomplete right bundle branch block and sinus tachycardia. Computed tomography pulmonary angiography revealed a three-cm pericardial effusion. Transthoracic echocardiography confirmed this finding and revealed a mass in the right ventricle (RV) extending into the outflow tract and infiltrating the free wall. The RV was dilated with an estimated RV systolic pressure of 37 mmHg. Pericardiocentesis yielded nearly one liter of serosanguinous fluid with non-diagnostic cytology. Partial median sternotomy with biopsy showed pathologic findings consistent with metastatic urothelial carcinoma, plasmacytoid variant. A PET scan showed increased uptake exclusively in the heart. The oncology team discussed options with the patient including chemotherapy and palliative care. The patient decided to withhold further therapy and went home with hospice care. He died two months later. DISCUSSION: Bladder cancer is the fourth most common cancer in men in the United States. Most patients (69%) with metastatic bladder cancer have multiple organs involved; conversely, our patient had a PET scan indicating his disease was localized to the heart. Plasmacytoid urothelial carcinoma is a rare subtype of bladder cancer, and is estimated to make up less than three percent of all invasive bladder carcinomas. At the time of this publication we are aware of only three other reported instances of isolated cardiac metastasis with urothelial bladder origin; none of which were the plasmacytoid variant. CONCLUSION: This case highlights a previously unreported presentation of plasmacytoid urothelial carcinoma. Clinicians must remember that even superficial cancers can have significant metastatic potential.

MR-compatible treadmill for exercise stress cardiac magnetic resonance imaging.

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.

Noninvasive imaging of prosthetic cardiac devices.

The major advances in cardiovascular care can be linked to the combined growth of advanced imaging modalities and the variety of treatment options available for patients with complex structural, acquired and congenital, valvular, myocardial and aortic diseases. Paralleling this growth are the number and spectrum of complications - such as device failures and infections - that these patients will inevitably encounter. The keys to successful implementation of advanced cardiac therapy are the real-time images, 3D reconstructions, and the hemodynamic and tissue profiles that can be obtained to evaluate these patients and their devices. We will review the roles of echocardiography, multidetector computed tomography and MRI in the evaluation of normal and abnormal cardiac device function.

Real-time cine and myocardial perfusion with treadmill exercise stress cardiovascular magnetic resonance in patients referred for stress SPECT.

BACKGROUND: To date, stress cardiovascular magnetic resonance (CMR) has relied on pharmacologic agents, and therefore lacked the physiologic information available only with exercise stress. METHODS: 43 patients age 25 to 81 years underwent a treadmill stress test incorporating both Tc99m SPECT and CMR. After rest Tc99m SPECT imaging, patients underwent resting cine CMR. Patients then underwent in-room exercise stress using a partially modified treadmill. 12-lead ECG monitoring was performed throughout. At peak stress, Tc99m was injected and patients rapidly returned to their prior position in the magnet for post-exercise cine and perfusion imaging. The patient table was pulled out of the magnet for recovery monitoring. The patient was sent back into the magnet for recovery cine and resting perfusion followed by delayed post-gadolinium imaging. Post-CMR, patients went to the adjacent SPECT lab to complete stress nuclear imaging. Each modality's images were reviewed blinded to the other's results. RESULTS: Patients completed on average 9.3 +/- 2.4 min of the Bruce protocol. Stress cine CMR was completed in 68 +/- 14 sec following termination of exercise, and stress perfusion CMR was completed in 88 +/- 8 sec. Agreement between SPECT and CMR was moderate (kappa = 0.58). Accuracy in eight patients who underwent coronary angiography was 7/8 for CMR and 5/8 for SPECT (p = 0.625). Follow-up at 6 months indicated freedom from cardiovascular events in 29/29 CMR-negative and 33/34 SPECT-negative patients. CONCLUSIONS: Exercise stress CMR including wall motion and perfusion is feasible in patients with suspected ischemic heart disease. Larger clinical trials are warranted based on the promising results of this pilot study to allow comparative effectiveness studies of this stress imaging system vs. other stress imaging modalities.

Cardiac magnetic resonance with edema imaging identifies myocardium at risk and predicts worse outcome in patients with non-ST-segment elevation acute coronary syndrome.

OBJECTIVES: The aim of this study was to define the prevalence and significance of myocardial edema in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). BACKGROUND: Most patients with NSTE-ACS undergo angiography, yet not all have obstructive coronary artery disease (CAD) requiring revascularization. Identifying patients with myocardium at risk could enhance the effectiveness of an early invasive strategy. Cardiac magnetic resonance (CMR) can demonstrate edematous myocardium subjected to ischemia but has not been used to evaluate NSTE-ACS patients. METHODS: One hundred consecutive patients with NSTE-ACS were prospectively enrolled to undergo 30-min CMR, including T2-weighted edema imaging and late gadolinium enhancement before coronary angiography. Clinical management including revascularization decision-making was performed without CMR results. RESULTS: Of 88 adequate CMR studies, 57 (64.8%) showed myocardial edema. Obstructive CAD requiring revascularization was present in 87.7% of edema-positive patients versus 25.8% of edema-negative patients (p < 0.001). By multiple logistic regression analysis after adjusting for late gadolinium enhancement, perfusion, and wall motion scores, TIMI risk score was not predictive of obstructive CAD. Conversely, an increase in T2 score by 1 U increased the odds of subsequent coronary revascularization by 5.70 times (95% confidence interval: 2.38 to 13.62, p < 0.001). Adjusting for peak troponin-I, patients with edema showed a higher hazard of a cardiovascular event or death within 6 months after NSTE-ACS compared with those without edema (hazard ratio: 4.47, 95% confidence interval: 1.00 to 20.03; p = 0.050). CONCLUSIONS: In NSTE-ACS patients, rapid CMR identifies reversibly injured myocardium due to obstructive CAD and predicts worse outcomes. Identifying myocardium at risk may help direct appropriate patients toward early invasive management.

Lipomatous hypertrophy of the intraatrial septum resulting in right atrial inflow obstruction and atrial flutter.

Atrial arrhythmias can occasionally be associated with atrial structural abnormalities that may require sophisticated diagnostic imaging for management. Lipomatous hypertrophy of the intraatrial septum is generally considered a benign fatty infiltrative process usually limited to the atrial septum. We present a rare case of lipomatous hypertrophy of the intraatrial septum associated with atrial flutter and right atrial inflow obstruction in which atrial reconstruction alleviated not only the obstruction but also helped control a challenging arrhythmia.

A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents (P = 0.037, OR = 6). Probands were more likely to carry an additional large copy-number variant when compared to matched controls (10 of 42 cases, P = 5.7 x 10(-5), OR = 6.6). The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease.

Gender-related differences in coronary artery dimensions: a volumetric analysis.

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.