Temporal patterns of gut microbiota in lemurs (Eulemur rubriventer) living in intact and disturbed habitats in a novel sample type.

The gut microbiome is a plastic phenotype; gut microbial composition is highly variable across an individual host's lifetime and between host social groups, and this variation has consequences for host health. However, we do not yet fully understand how longitudinal microbial dynamics and their social drivers may be influenced by ecological stressors, such as habitat degradation. Answering these questions is difficult in most wild animal systems, as it requires long-term collections of matched host, microbiome, and environmental trait data. To test if temporal and social influences on microbiome composition differ by the history of human disturbance, we leveraged banked, desiccated fecal samples collected over 5 months in 2004 from two ecologically distinct populations of wild, red-bellied lemurs (Eulemur rubriventer) that are part of a long-term study system. We found that social group explained more variation in microbiome composition than host population membership did, and that temporal variation in common microbial taxa was similar between populations, despite differences in history of human disturbance. Furthermore, we found that social group membership and collection month were both more important than individual lemur identity. Taken together, our results suggest that synchronized environments use can lead to synchronized microbial dynamics over time, even between habitats of varying quality, and that desiccated samples could become a viable approach for studying primate gut microbiota. Our work opens the door for other projects to utilize historic biological sample data sets to answer novel temporal microbiome questions in an ecological context.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

Early triage echocardiography to predict outcomes in patients admitted with COVID-19: a multicenter study.

INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, especially in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside triage echocardiography (echo), in patients admitted to emergency departments (ED) in the US with COVID-19. We also assessed the feasibility of using cloud imaging for sharing and interpreting echocardiograms. METHODS: Patients admitted to three reference EDs with confirmed COVID-19 underwent triage echo within 72 h of symptom onset with remote interpretation. Clinical and laboratory data, as well as COVID-19 symptoms, were collected. The association between echo variables, demographics and clinical data with all-cause hospital mortality and intensive care unit (ICU) admission was assessed using logistic regression. RESULTS: Three hundred ninety-nine patients were enrolled, 41% women, with a mean age of 62±16 years. Mean oxygen saturation on presentation was 92.3± 9.2%. Compared to in-hospital survivors, non-survivors were older, had lower oxygen saturation on presentation, were more likely to have a chronic condition and had lower LV ejection fraction (50.3±19.7% vs. 58.0±13.6%) (P < .05). In the cohort, 101 (25%) patients had moderate/severe LV dysfunction, 131 (33%) had moderate/severe RV dysfunction. Advanced age and lower oxygen saturation were independently associated with death and ICU admission. LV and RV function, or other echo variables, were not independent predictors of outcomes. CONCLUSION: In patients admitted with COVID-19 undergoing early echo triage, the independent predictors of death and ICU admission were age and oxygen saturation. The inclusion of echo variables did not improve prediction of unfavorable outcomes.

Myocardial Injury in Severe COVID-19 Compared With Non-COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in coronavirus disease 2019 (COVID-19). We aimed to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared with acute respiratory distress syndrome (ARDS) unrelated to COVID-19. METHODS: We included intubated patients with COVID-19 from 5 hospitals between March 15 and June 11, 2020, with troponin levels assessed. We compared them with patients from a cohort study of myocardial injury in ARDS and performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. In addition, we performed linear regression to identify clinical factors associated with myocardial injury in COVID-19. RESULTS: Of 243 intubated patients with COVID-19, 51% had troponin levels above the upper limit of normal. Chronic kidney disease, lactate, ferritin, and fibrinogen were associated with myocardial injury. Mortality was 22.7% among patients with COVID-19 with troponin under the upper limit of normal and 61.5% for those with troponin levels >10 times the upper limit of normal (P<0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex, and multisystem organ dysfunction. Compared with patients with ARDS without COVID-19, patients with COVID-19 were older and had higher creatinine levels and less favorable vital signs. After adjustment, COVID-19-related ARDS was associated with lower odds of myocardial injury compared with non-COVID-19-related ARDS (odds ratio, 0.55 [95% CI, 0.36-0.84]; P=0.005). CONCLUSIONS: Myocardial injury in severe COVID-19 is a function of baseline comorbidities, advanced age, and multisystem organ dysfunction, similar to traditional ARDS. The adverse prognosis of myocardial injury in COVID-19 relates largely to multisystem organ involvement and critical illness.

Utilization of cardiovascular magnetic resonance (CMR) imaging for resumption of athletic activities following COVID-19 infection: an expert consensus document on behalf of the American Heart Association Council on Cardiovascular Radiology and Intervention (CVRI) Leadership and endorsed by the Society for Cardiovascular Magnetic Resonance (SCMR).

The global pandemic of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory suyndrome coronavirus 2 (SARS-CoV-2) is now entering its 4th year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. While pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. Given the broad swath of the population infected with COVID-19, the large number of affected professional, collegiate, and amateur athletes raises concern regarding the safe resumption of athletic activity (return to play, RTP) following resolution of infection. A variety of different testing combinations that leverage the electrocardiogram, echocardiography, circulating cardiac biomarkers, and cardiovascular magnetic resonance (CMR) imaging have been proposed and implemented to mitigate risk. CMR in particular affords high sensitivity for myocarditis but has been employed and interpreted non-uniformly in the context of COVID-19 thereby raising uncertainty as to the generalizability and clinical relevance of findings with respect to RTP. This consensus document synthesizes available evidence to contextualize the appropriate utilization of CMR in the RTP assessment of athletes with prior COVID-19 infection to facilitate informed, evidence-based decisions, while identifying knowledge gaps that merit further investigation.

Left ventricular myocardial work indices in pediatric hypertension: correlations with conventional echocardiographic assessment and subphenotyping.

Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thus overcoming the limitations of load dependency traditionally encountered with LV fractional shortening (LVFS), ejection fraction (LVEF), and global longitudinal strain (GLS). However, data on MW in the pediatric population with hypertension are lacking. Conventional markers of LV function and MW indices were obtained from 88 echocardiographic examinations in 76 children with hypertension (47 males, 15.5 ± 2.96 years). When compared with a previously published cohort of 52 healthy controls, global work index (GWI) and global constructive work (GCW) were both significantly elevated while LVEF and GLS were not impaired but rather mildly increased. On multivariable analysis, GWI was correlated with systolic blood pressure (slope = + 16, p < 0.001) and GLS (slope = -100, p < 0.001), while GCW was correlated with systolic blood pressure (slope = + 18, p < 0.001), GLS (slope = -101, p < 0.001), male sex (slope = -75, p = 0.016), and LV mass (slope = -0.93, p < 0.001). Global wasted work (GWW) was correlated with age at echo visit (slope = -4.5, p = 0.005) and GLS (slope = + 5.5, p < 0.001). The opposite occurred for global work efficiency (GWE; slope = + 0.20, p = 0.011, and slope = -0.48, p < 0.001, respectively). Principal component analysis and k-means clustering revealed 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.    Conclusion: Non-invasive MW shows a good correlation with conventional markers of LV function and may help refine the assessment of hypertensive heart disease in children. What is Known: • Myocardial work (MW) is a novel parameter that incorporates non-invasive estimates of left ventricular (LV) systolic pressure into the interpretation of strain, thereby accounting for both deformation and afterload. • Although the usefulness of MW in the assessment of myocardial function beyond conventional markers has been demonstrated in various clinical populations, data in the pediatric population with hypertension are currently lacking. What is New: • Compared to normal values in healthy children, global work index and global constructive work were increased in those with hypertension, while LV ejection fraction and global longitudinal strain were not impaired. • Machine learning identified 4 subphenotypes which differed in terms of etiology, afterload, and compensation stage of the disease.

Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

BACKGROUND: The ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) is a validated index of right ventricular-pulmonary arterial (RV-PA) coupling with prognostic value. We determined the predictive value of TAPSE/PASP ratio and adverse clinical outcomes in hospitalized patients with COVID-19. METHODS: Two hundred and twenty-nine consecutive hospitalized racially/ethnically diverse adults (≥18 years of age) admitted with COVID-19 between March and June 2020 with clinically indicated transthoracic echocardiograms (TTE) that included adequate tricuspid regurgitation (TR) velocities for calculation of PASP were studied. The exposure of interest was impaired RV-PA coupling as assessed by TAPSE/PASP ratio. The primary outcome was in-hospital mortality. Secondary endpoints comprised of ICU admission, incident acute respiratory distress syndrome (ARDS), and systolic heart failure. RESULTS: One hundred and seventy-six patients had both technically adequate TAPSE measurements and measurable TR velocities for analysis. After adjustment for age, sex, BMI, race/ethnicity, diabetes mellitus, and smoking status, log(TAPSE/PASP) had a significantly inverse association with ICU admission (p = 0.015) and death (p = 0.038). ROC analysis showed the optimal cutoff for TAPSE/PASP for death was 0.51 mm mmHg-1 (AUC = 0.68). Unsupervised machine learning identified two groups of echocardiographic function. Of all echocardiographic measures included, TAPSE/PASP ratio was the most significant in predicting in-hospital mortality, further supporting its significance in this cohort. CONCLUSION: Impaired RV-PA coupling, assessed noninvasively via the TAPSE/PASP ratio, was predictive of need for ICU level care and in-hospital mortality in hospitalized patients with COVID-19 suggesting utility of TAPSE/PASP in identification of poor clinical outcomes in this population both by traditional statistical and unsupervised machine learning based methods.

HIV and Global Cardiovascular Health.

PURPOSE OF REVIEW: Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. RECENT FINDINGS: PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.

Phase contrast coronary blood velocity mapping with both high temporal and spatial resolution using triggered Golden Angle rotated Spiral k-t Sparse Parallel imaging (GASSP) with shifted binning.

PURPOSE: High temporal and spatial resolutions are required for coronary blood flow measures. Current spiral breath-hold phase contrast (PC) MRI at 3T focus on either high spatial or high temporal resolution. We propose a golden angle (GA) rotated Spiral k-t Sparse Parallel imaging (GASSP) sequence for both high spatial (0.8 mm) and high temporal (<21 ms) resolutions. METHODS: GASSP PC data are acquired in left anterior descending and right coronary arteries of eight healthy subjects. Binning of GA rotated spiral data into cardiac frames may lead to large k-space gaps. To reduce those gaps, the binning window is shifted and a triggered GA scheme that resets the rotation angle every heartbeat is proposed. The gap reductions are evaluated in simulations and all subjects. Peak systolic velocity (PSV), peak diastolic velocity (PDV), coronary blood flow rate, and vessel area are validated against two reference scans, and repeatability/reproducibility are determined. RESULTS: Shifted binning reduced the mean k-space gaps of the triggered GA scheme by 14°-22° in simulations and about 20° in vivo. The k-space gap across three cardiac frames was reduced with the triggered GA scheme compared to the standard GA scheme (35.3°± 3.6° vs. 43°± 13.7°, t-test P = .04). PSV, PDV, flow rate, and area had high intra-scan repeatability (0.92 ≤ intraclass correlation coefficient [ICC] ≤ 0.99), and inter-scan (0.78 ≤ ICC ≤ 0.91) and intra-observer (0.91 ≤ ICC ≤ 0.98) reproducibility. CONCLUSION: GASSP enables single breath-hold coronary PC MRI with high temporal and spatial resolutions. Shifted binning and a triggered GA scheme reduce k-space gaps. Quantitative coronary flow metrics are highly reproducible, especially within the same scanning session.

Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients With Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-19 (COVID-19) has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain on speckle-tracking echocardiography in hospitalized patients with COVID-19 and subsequently aimed to identify characteristics of affected patients. We hypothesized that patients with COVID-19 with reduced basal LV strain would demonstrate elevated cardiac biomarkers. METHODS AND RESULT: Eighty-one consecutive patients with COVID-19 underwent speckle-tracking echocardiography. Those with poor quality speckle-tracking echocardiography (n = 2) or a known LV ejection fraction of <50% (n = 4) were excluded. Patients with an absolute value basal longitudinal strain of <13.9% (2 standard deviations below normal) were designated as cases (n = 39); those with a basal longitudinal strain of ≥13.9% were designated as controls (n = 36). Demographics and clinical variables were compared. Of 75 included patients (mean age 62 ± 14 years, 41% women), 52% had reduced basal strain. Cases had higher body mass index (median 34.1; interquartile range 26.5-37.9 kg/m2 vs median 26.9, interquartile range, 24.8-30.0 kg/m2, P = .009), and greater proportions of Black (74% vs 36%, P = .0009), hypertensive (79% vs 56%, P = .026), and diabetic patients (44% vs 19%, P = .025) compared with controls. Troponin and N-terminal pro-brain natriuretic peptide levels trended higher in cases, but were not significantly different. CONCLUSIONS: Reduced basal LV strain is common in patients with COVID-19. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Multimodality Imaging for Cardiac Evaluation in Patients with COVID-19.

PURPOSE OF REVIEW: A growing number of cardiovascular manifestations resulting from the novel SARS-CoV-2 coronavirus (COVID-19) have been described since the beginning of this global pandemic. Acute myocardial injury is common in this population and is associated with higher rates of morbidity and mortality. The focus of this review centers on the recent applications of multimodality imaging in the diagnosis and management of COVID-19-related cardiovascular conditions. RECENT FINDINGS: In addition to standard cardiac imaging techniques such as transthoracic echocardiography, other modalities including computed tomography and cardiac magnetic resonance imaging have emerged as useful adjuncts in select patients with COVID-19 infection, particularly those with suspected ischemic and nonischemic myocardial injury. Data have also emerged suggesting lasting COVID-19 subclinical cardiac effects, which may have long-term prognostic implications. With the spectrum of COVID-19 cardiovascular manifestations observed thus far, it is important for clinicians to recognize the role, strengths, and limitations of multimodality imaging techniques in this patient population.

Sex-Specific Plaque Signature: Uniqueness of Atherosclerosis in Women.

PURPOSE OF REVIEW: Cardiovascular disease is a leading cause of morbidity and mortality in both men and women, although there are notable differences in presentation between men and women. Atherosclerosis remains the predominant driver of coronary heart disease in both sexes; however, sex differences in atherosclerosis should be investigated further to understand clinical manifestations between men and women. RECENT FINDINGS: There are sex differences in the prevalence, progression, and prognostic impact of atherosclerosis. Furthermore, developing evidence demonstrates unique differences in atherosclerotic plaque characteristics between men and women on both noninvasive and invasive imaging modalities. Coronary microvascular dysfunction may be present even if no obstructive lesions are found. Most importantly, non-obstructive coronary artery disease is associated with a heightened risk of future adverse cardiovascular events and should not be ignored. The distinct plaque signature in women should be recognized, and optimal preventive strategies should be performed for both sexes.

Society for Cardiovascular Magnetic Resonance (SCMR) guidance for re-activation of cardiovascular magnetic resonance practice after peak phase of the COVID-19 pandemic.

During the peak phase of the COVID-19 pandemic, alterations of standard operating procedures were necessary for health systems to protect patients and healthcare workers and ensure access to vital hospital resources. As the peak phase passes, re-activation plans are required to safely manage increasing clinical volumes. In the context of cardiovascular magnetic resonance (CMR), re-activation objectives include continued performance of urgent CMR studies and resumption of CMR in patients with semi-urgent and elective indications in an environment that is safe for both patients and health care workers.

Precision and accuracy of cross-sectional area measurements used to measure coronary endothelial function with spiral MRI.

PURPOSE: Coronary endothelial function (CEF) reflects vascular health and conventional invasive CEF measures predict cardiovascular events. MRI can now noninvasively measure CEF by quantifying coronary artery cross-sectional area changes in response to isometric handgrip exercise, an endothelial-dependent stressor. Area changes (10 to 20% in healthy; 2 to -12% in impaired vessels) are only a few imaging voxels because of MRI's limited spatial resolution. Here, with numerical simulations and phantom studies, we test whether Fourier interpolation enables sub-pixel area measurement precision and determine the smallest detectable area change using spiral MRI. METHODS: In vivo coronary SNR with the currently used CEF protocol at 3T was measured in 7 subjects for subsequent in vitro work. Area measurements of circular vessels were simulated by varying partial volume, vessel diameter, voxel size, SNR, and Fourier interpolation factor. A phantom with precision-drilled holes (diameters 3-3.42 mm) was imaged 10 times with the current CEF protocol (voxel size, Δx = 0.89 mm) and a high-resolution protocol (Δx = 0.6 mm) to determine precision, accuracy, and the smallest detectable area changes. RESULTS: In vivo coronary SNR ranged from 30-76. Eight-fold Fourier interpolation improved area measurement precision by a factor 6.5 and 4.9 in the simulations and phantom scans, respectively. The current CEF protocol can detect mean area changes of 4-5% for SNR above 30, and 3-3.5% for SNR above 40 with a higher-resolution protocol. CONCLUSION: Current CEF spiral MRI with in vivo SNR allows detection of a 4-5% area change and Fourier interpolation improves precision several-fold to sub-voxel dimensions.

Delayed endothelialization of watchman device identified with cardiac CT.

BACKGROUND: Left atrial appendage (LAA) closure with the Watchman device is increasingly used in patients with nonvalvular atrial fibrillation for stroke prevention. Though clinical trials have shown a similar combined risk of ischemic and hemorrhagic stroke, there is an increased risk of ischemic stroke in patients with a Watchman device compared with anticoagulation. Some ischemic strokes are related to a device-related thrombus (DRT), which may be attributable to delayed endothelialization of exposed fabric and metal. METHODS AND RESULTS: Patients undergoing Watchman LAA occlusion between January 2016 and June 2018 were enrolled in a prospective registry. From this cohort, 46 patients who had both transesophageal echocardiogram (TEE) and computed tomography (CT) at 45 days follow-up were selected for this study. The degree of LAA occlusion and type of leak were assessed by CT and TEE. TEE identified no patients with a significant (>5 mm) peri-device leak, 27 (58.6%) with nonsignificant peri-device leak (<5 mm), and 19 (41.4%) with complete occlusion. CT identified contrast in the LAA in 28 (60%) patients. However, in 10 (21.8%) of these patients, contrast entered the LAA through the fabric rather than around the device. No DRT were identified. CONCLUSION: These data reveal that the Watchman device remains porous 6 weeks after implantation in a substantial percentage of patients, suggesting delayed endothelialization of the device. Cardiac CT may help to differentiate between peri-device and trans-fabric leak. Additional studies are required to test whether prolonged anticoagulation in patients with trans-fabric leak may help to reduce the risk of DRT and ischemic stroke.

The influence of febuxostat on coronary artery endothelial dysfunction in patients with coronary artery disease: A phase 4 randomized, placebo-controlled, double-blind, crossover trial.

BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.

Self-gated golden angle spiral cine MRI for coronary endothelial function assessment.

PURPOSE: Depressed coronary endothelial function (CEF) is a marker for atherosclerotic disease, an independent predictor of cardiovascular events, and can be quantified non-invasively with ECG-triggered spiral cine MRI combined with isometric handgrip exercise (IHE). However, MRI-CEF measures can be hindered by faulty ECG-triggering, leading to prolonged breath-holds and degraded image quality. Here, a self-gated golden angle spiral method (SG-GA) is proposed to eliminate the need for ECG during cine MRI. METHODS: SG-GA was tested against retrospectively ECG-gated golden angle spiral MRI (ECG-GA) and gold-standard ECG-triggered spiral cine MRI (ECG-STD) in 10 healthy volunteers. CEF data were obtained from cross-sectional images of the proximal right and left coronary arteries in a 3T scanner. Self-gating heart rates were compared to those from simultaneous ECG-gating. Coronary vessel sharpness and cross-sectional area (CSA) change with IHE were compared among the 3 methods. RESULTS: Self-gating precision, accuracy, and correlation-coefficient were 7.7 ± 0.5 ms, 9.1 ± 0.7 ms, and 0.93 ± 0.01, respectively (mean ± standard error). Vessel sharpness by SG-GA was equal or higher than ECG-STD (rest: 63.0 ± 1.7% vs. 61.3 ± 1.3%; exercise: 62.6 ± 1.3% vs. 56.7 ± 1.6%, P < 0.05). CSA changes were in agreement among the 3 methods (ECG-STD = 8.7 ± 4.0%, ECG-GA = 9.6 ± 3.1%, SG-GA = 9.1 ± 3.5%, P = not significant). CONCLUSION: CEF measures can be obtained with the proposed self-gated high-quality cine MRI method even when ECG is faulty or not available. Magn Reson Med 80:560-570, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Local coronary wall eccentricity and endothelial function are closely related in patients with atherosclerotic coronary artery disease.

BACKGROUND: Coronary endothelial function (CEF) in patients with coronary artery disease (CAD) varies among coronary segments in a given patient. Because both coronary vessel wall eccentricity and coronary endothelial dysfunction are predictors of adverse outcomes, we hypothesized that local coronary endothelial dysfunction is associated with local coronary artery eccentricity. METHODS: We used 3 T coronary CMR to measure CEF as changes in coronary cross-sectional area (CSA) and coronary blood flow (CBF) during isometric handgrip exercise (IHE), a known endothelial-dependent stressor, in 29 patients with known CAD and 16 healthy subjects. Black-blood MRI quantified mean coronary wall thickness (CWT) and coronary eccentricity index (EI) and CEF was determined in the same segments. RESULTS: IHE-induced changes in CSA and CBF in healthy subjects (10.6 ± 6.6% and 38.3 ± 29%, respectively) were greater than in CAD patients 1.3 ± 7.7% and 6.5 ± 19.6%, respectively, p < 0.001 vs. healthy for both measures), as expected. Mean CWT and EI in healthy subjects (1.1 ± 0.3 mm 1.9 ± 0.5, respectively) were less than those in CAD patients (1.6 ± 0.4 mm, p < 0.0001; and 2.6 ± 0.6, p = 0.006 vs. healthy). In CAD patients, we observed a significant inverse relationship between stress-induced %CSA change and both EI (r = -0.60, p = 0.0002), and CWT (r = -0.54, p = 0.001). Coronary EI was independently and significantly related to %CSA change with IHE even after controlling for mean CWT (adjusted r = -0.69, p = 0.0001). For every unit increase in EI, coronary CSA during IHE is expected to change by -6.7 ± 9.4% (95% confidence interval: -10.3 to -3.0, p = 0.001). CONCLUSION: There is a significant inverse and independent relationship between coronary endothelial macrovascular function and the degree of local coronary wall eccentricity in CAD patients. Thus anatomic and physiologic indicators of high-risk coronary vascular pathology are closely related. The noninvasive identification of coronary eccentricity and its relationship with underlying coronary endothelial function, a marker of vascular health, may be useful in identifying high-risk patients and culprit lesions.