Assessment of Papillary Muscle Infarction with Dark-Blood Delayed Enhancement Cardiac MRI in Canines and Humans.

Background The relationship between papillary muscle infarction (papMI) and the culprit coronary lesion has not been fully investigated. Delayed enhancement cardiac MRI may detect papMI, yet its accuracy is unknown. Flow-independent dark-blood delayed enhancement (FIDDLE) cardiac MRI has been shown to improve the detection of myocardial infarction adjacent to blood pool. Purpose To assess the diagnostic performance of delayed enhancement and FIDDLE cardiac MRI for the detection of papMI, and to investigate the prevalence of papMI and its relationship to the location of the culprit coronary lesion. Materials and Methods A prospective canine study was used to determine the accuracy of conventional delayed enhancement imaging and FIDDLE imaging for detection of papMI, with pathology-based findings as the reference standard. Participants with first-time myocardial infarction with a clear culprit lesion at coronary angiography were prospectively enrolled at a single hospital from 2015 to 2018 and compared against control participants with low Framingham risk scores. In canines, diagnostic accuracy was calculated for delayed enhancement and FIDDLE imaging. Results In canines (n = 27), FIDDLE imaging was more sensitive (100% [23 of 23] vs 57% [13 of 23], P < .001) and accurate (100% [54 of 54] vs 80% [43 of 54], P = .01) than delayed enhancement imaging for detection of papMI. In 43 participants with myocardial infarction (mean age, 56 years ± 16 [SD]; 28 men), the infarct-related artery was the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery in 47% (20 of 43), 26% (11 of 43), and 28% (12 of 43), respectively. The prevalence of anterior papMI was lower than posterior papMI (37% [16 of 43 participants] vs 44% [19 of 43 participants]) despite more LAD culprit lesions. Culprits leading to papMI were restricted to a smaller "at-risk" portion of the coronary tree for anterior papMI (subtended first diagonal branch of the LAD or first marginal branch of the LCX) compared with posterior (subtended posterior descending artery or third obtuse marginal branch of the LCX). Culprits within these at-risk portions were predictive of papMI at a similar rate (anterior, 83% [15 of 18 participants] vs posterior, 86% [18 of 21 participants]). Conclusion Flow-independent dark-blood delayed enhancement cardiac MRI, unlike conventional delayed enhancement cardiac MRI, was highly accurate in the detection of papillary muscle infarction (papMI). Anterior papMI was less prevalent than posterior papMI, most likely due to culprit lesions being restricted to a smaller portion of the coronary tree rather than because of redundant, dual vascular supply. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Assessment of myocardial lipomatous metaplasia using an optimized out-of-phase cine steady-state free-precession sequence: Validation and clinical implementation.

Myocardial lipomatous metaplasia, which can serve as substrate for ventricular arrhythmias, is usually composed of regions in which there is an admixture of fat and nonfat tissue. Although dedicated sequences for the detection of fat are available, it would be time-consuming and burdensome to routinely use these techniques to image the entire heart of all patients as part of a typical cardiac MRI exam. Conventional steady-state free-precession (SSFP) cine imaging is insensitive to detecting myocardial regions with partial fatty infiltration. We developed an optimization process for SSFP imaging to set fat signal consistently "out-of-phase" with water throughout the heart, so that intramyocardial regions with partial volume fat would be detected as paradoxically dark regions. The optimized SSFP sequence was evaluated using a fat phantom, through simulations, and in 50 consecutive patients undergoing clinical cardiac MRI. Findings were validated using standard Dixon gradient-recalled-echo (GRE) imaging as the reference. Phantom studies of test tubes with diverse fat concentrations demonstrated good agreement between measured signal intensity and simulated values calculated using Bloch equations. In patients, a line of signal cancellation at the interface between myocardium and epicardial fat was noted in all cases, confirming that SSFP images were consistently out-of-phase throughout the entire heart. Intramyocardial dark regions identified on out-of-phase SSFP images were entirely dark throughout in 33 patients (66%) and displayed an India-ink pattern in 17 (34%). In all cases, dark intramyocardial regions were also seen in the same locations on out-of-phase GRE and were absent on in-phase GRE, confirming that these regions represent areas with partial fat. In conclusion, if appropriately optimized, SSFP cine imaging allows for consistent detection of myocardial fatty metaplasia in patients undergoing routine clinical cardiac MRI without the need for additional image acquisitions using dedicated fat-specific sequences.

Double spectral attenuated inversion recovery (DSPAIR)-an efficient fat suppression technique for late gadolinium enhancement at 3 tesla.

Despite clinical use of late gadolinium enhancement (LGE) for two decades, an efficient, robust fat suppression (FS) technique still does not exist for this CMR mainstay. In ischemic and non-ischemic heart disease, differentiating fibrotic tissue from infiltrating and adjacent fat is crucial. Multiple groups have independently developed an FS technique for LGE, double spectral attenuated inversion recovery (DSPAIR), but no comprehensive evaluation was performed. This study aims to fill this gap. DSPAIR uses two SPAIR pulses and one non-selective IR pulse to enable FS LGE, including compatibility with phase sensitive inversion recovery (PSIR). We implemented a magnitude (MAGN) and a PSIR variant and compared them with LGE without FS (CONTROL) and with spectral presaturation with inversion recovery (SPIR) in simulations, phantoms, and patients. Fat magnetization by SPIR, MAGN DSPAIR, and PSIR DSPAIR was simulated as a function of pulse B1 , readout (RO) pulse number, and fat TI . A phantom with fat, fibrosis, and myocardium compartments was imaged using all FS methods and modifying pulse B1 , RO pulse number, and heart rate. Signal was measured in SNR units. Fat, myocardium, and fibrosis SNR and fibrosis-to-fat CNR were obtained. Patient images were acquired with all FS techniques. Fat, myocardium, and fibrosis SNR, fibrosis-to-fat CNR, and image and FS quality were assessed. In the phantom, both DSPAIR variants provided superior FS compared with SPIR, independent of heart rate and RO pulse number. MAGN DSPAIR reduced fat signal by 99% compared with CONTROL, PSIR DSPAIR by 116%, and SPIR by 67% (25 RO pulses). In patients, both DSPAIR variants substantially reduced fat signal (MAGN DSPAIR by 87.1% ± 10.0%, PSIR DSPAIR by 130.5% ± 36.3%), but SPIR did not (35.8% ± 25.5%). FS quality was good to excellent for MAGN and PSIR DSPAIR, and moderate to poor for SPIR. DSPAIR provided highly effective FS across a wide range of parameters. PSIR DSPAIR performed best.

ECG-gated MR angiography provides better reproducibility for standard aortic measurements.

OBJECTIVE: Cardiac motion and aortic pulsatility can affect the image quality of 3D contrast-enhanced MR angiography (CE-MRA). The addition of ECG gating improves image quality; however, no studies have directly linked image quality improvements to clinically used measures. In this study, we directly compared diameter measurements in the same patient from ECG-gated to non-gated CE-MRA to evaluate the impact of ECG gating upon measurement reproducibility. METHODS: Fifty-three patients, referred for thoracic aortic angiography, were enrolled and underwent both non-gated and ECG-gated CE-MRA. Two readers independently measured vessel diameter, image quality, and vessel sharpness at the sinus of Valsalva (SOV), sinotubular junction (STJX), ascending aorta (AAO), distal aortic arch (DLSA), and descending aorta (DAO). Measurement reliability and reproducibility were compared between methods. RESULTS: Image quality with ECG gating was rated significantly higher at the SOV (3.2 ± 0.9 vs 1.2 ± 1.0, p < 0.0001), STJX (3.4 ± 0.7 vs 1.8 ± 1.0, p < 0.0001), AAO (3.5 ± 0.6 vs 1.7 ± 1.1 p < 0.0001), DLSA (4.0 ± 0.1 vs 3.6 ± 0.7, p = 0.006), and DAO (4.0 ± 0.1 vs 3.4 ± 0.9 p < 0.0001) than for non-gated studies. Bland-Altman analyses demonstrated that inter- and intra-observer variability was significantly smaller for ECG-gated MRA at the SOV and AAO. For the non-gated images at the SOV, the 95% limits of agreement for both inter- and intra-observer variability exceeded the growth-rate cutoff for surgical repair (0.5 cm). At the DAO, variability was similar between the two techniques. CONCLUSION: ECG-gated CE-MRA resulted in improved reproducibility in aortic root and ascending aortic measurements. These data suggest that ECG-gated CE-MRA should be used for the serial assessment of the ascending thoracic aorta. KEY POINTS: • ECG-gated CE-MRA improves the reproducibility and repeatability of measurements of the ascending aorta. • With non-gated CE-MRA, pulsatile motion in the proximal aorta results in significant variability in measurement reproducibility.

A short form of the Recovery Assessment Scale-Domains and Stages: Development and validation among adults with anxiety disorders.

The Recovery Assessment Scale-Domains and Stages (RAS-DS) is a 38-item self-report instrument measuring recovery from serious mental illness. We explored the suitability of the RAS-DS for individuals with anxiety disorders. A parsimonious short form of the scale was developed. Participants with anxiety disorder symptoms (N = 295) completed the RAS-DS, DASS-21 and GAD-7. Confirmatory factor analysis supported the expected four-factor structure. Associations with related scales exhibited the expected pattern supporting construct validity in this population. The Recovery Assessment Scale-Short Form (RAS-SF) was derived by inspection of factor loadings and modification indices, yielding a 20-item scale with five items per subscale. Strong correlations between subscales confirmed the total score represented a valid overarching measure of recovery. The present study indicates that recovery is pertinent to individuals with anxiety disorders. Development of the short-form RAS-SF affords opportunity for routine measurement of recovery in populations with anxiety and other high prevalence conditions.

Comparison of magnetization transfer-preparation and T2-preparation for dark-blood delayed-enhancement imaging.

Recently developed dark-blood techniques such as Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE) allow simultaneous visualization of tissue contrast-enhancement and blood-pool suppression. Critical to FIDDLE is the magnetization preparation, which accentuates differences between myocardium and blood-pool. Here, we compared magnetization transfer (MT)-preparation and T2-preparation for use with FIDDLE. Variants of FIDDLE were developed with MT- or T2-preparation modules and tested in 35 patients (11 at 1.5 T, 24 at 3 T). Images were acquired with each FIDDLE variant in an interleaved fashion 10 minutes after gadolinium administration with otherwise identical acquisition parameters. Images were visually and quantitatively assessed for artifacts and differences in right ventricle to left ventricle (RV-to-LV) blood-pool suppression. Bright artifacts, reflecting incomplete blood-pool suppression, were frequently observed in the left atrium with T2-preparation FIDDLE at 1.5 and 3 T (82% and up to 100% of patients, respectively). MT-preparation FIDDLE resulted in fewer patients with artifacts (0% at 1.5 T, 22% at 3 T; P < .01). Left atrial blood-pool signal was significantly more homogeneous with MT-preparation than with T2-preparation at 1.5 and 3 T (P < .001 for all comparisons). Visibly different RV-to-LV blood-pool suppression was observed with T2-preparation in 36% of patients at 1.5 T and up to 94% at 3 T. In these patients, RV blood-pool signal was elevated, reducing the conspicuity of the myocardial-RV blood-pool border. Conversely, there were no visible differences in RV-to-LV blood-pool suppression with MT-preparation. Quantitative assessment of differences in blood-pool suppression and blood-pool artifacts was consistent with visual analyses. We conclude that for dark blood-blood delayed-enhancement imaging of the heart, MT-preparation results in fewer bright blood-pool artifacts and more uniform blood-pool suppression than T2-preparation.

Suppression of ghost artifacts arising from long T1 species in segmented inversion-recovery imaging.

PURPOSE: We demonstrate an improved segmented inversion-recovery sequence that suppresses ghost artifacts arising from tissues with long T1 ( > 1.5 s). THEORY AND METHODS: Long T1 species such as pericardial fluid can create bright ghost artifacts in segmented, inversion-recovery MRI because of oscillations in longitudinal magnetization between segments. A single dummy acquisition at the beginning of the sequence can reduce oscillations; however, its effectiveness in suppressing long T1 artifacts is unknown. In this study, we systematically evaluated several test sequences, including a prototype (saturation post-pulse readout to eliminate spurious signal: SPPRESS) in simulations, phantoms, and patients. RESULTS: SPPRESS reduced artifact signal 90% ± 25% and 74% ± 28% compared with Control and Single-Dummy methods in phantoms. SPPRESS performed well at 1.5 Tesla (T) and 3T, with steady-state free precession (SSFP) and fast low-angle shot (FLASH) readout, with conventional and phase-sensitive reconstruction, and over a range of physiologic heart rates. A review of 100 consecutive clinical cardiac MRI scans revealed large fluid collections (eg, regions with long T1 ) in 14% of patients. In a prospectively enrolled cohort of 16 patients with visible long T1 fluids, SPPRESS appreciably reduced artifacts in all cases compared with Control and Single-Dummy methods. CONCLUSION: We developed and validated a new robust method, SPPRESS, for reducing artifacts due to long T1 species across a wide range of imaging and physiologic conditions. Magn Reson Med 78:1442-1451, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk.

RATIONALE: After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE: To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS: Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION: T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.

BACKGROUND: Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. MATERIALS AND METHODS: Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. RESULTS: LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. CONCLUSIONS: The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective.

The Impact of Cardiac Motion on Aortic Valve Flow Used in Computational Simulations of the Thoracic Aorta.

Advancements in image-based computational modeling are producing increasingly more realistic representations of vasculature and hemodynamics, but so far have not compensated for cardiac motion when imposing inflow boundary conditions. The effect of cardiac motion on aortic flow is important when assessing sequelae in this region including coarctation of the aorta (CoA) or regurgitant fraction. The objective of this investigation was to develop a method to assess and correct for the influence of cardiac motion on blood flow measurements through the aortic valve (AoV) and to determine its impact on patient-specific local hemodynamics quantified by computational fluid dynamics (CFD). A motion-compensated inflow waveform was imposed into the CFD model of a patient with repaired CoA that accounted for the distance traveled by the basal plane during the cardiac cycle. Time-averaged wall shear stress (TAWSS) and turbulent kinetic energy (TKE) values were compared with CFD results of the same patient using the original waveform. Cardiac motion resulted in underestimation of flow during systole and overestimation during diastole. Influences of inflow waveforms on TAWSS were greatest along the outer wall of the ascending aorta (AscAo) (∼30 dyn/cm2). Differences in TAWSS were more pronounced than those from the model creation or mesh dependence aspects of CFD. TKE was slightly higher for the motion-compensated waveform throughout the aortic arch. These results suggest that accounting for cardiac motion when quantifying blood flow through the AoV can lead to different conclusions for hemodynamic indices, which may be important if these results are ultimately used to predict patient outcomes.

Distribution of human-specific bacteroidales and fecal indicator bacteria in an urban watershed impacted by sewage pollution, determined using RNA- and DNA-based quantitative PCR assays.

The identification of fecal pollution sources is commonly carried out using DNA-based methods. However, there is evidence that DNA can be associated with dead cells or present as "naked DNA" in the environment. Furthermore, it has been shown that rRNA-targeted reverse transcription-quantitative PCR (RT-qPCR) assays can be more sensitive than rRNA gene-based qPCR assays since metabolically active cells usually contain higher numbers of ribosomes than quiescent cells. To this end, we compared the detection frequency of host-specific markers and fecal bacteria using RNA-based RT-qPCR and DNA-based qPCR methods for water samples collected in sites impacted by combined sewer overflows. As a group, fecal bacteria were more frequently detected in most sites using RNA-based methods. Specifically, 8, 87, and 85% of the samples positive for general enterococci, Enterococcus faecalis, and Enterococcus faecium markers, respectively, were detected using RT-qPCR, but not with the qPCR assay counterpart. On average, two human-specific Bacteroidales markers were not detected when using DNA in 12% of the samples, while they were positive for all samples when using RNA (cDNA) as the template. Moreover, signal intensity was up to three orders of magnitude higher in RT-qPCR assays than in qPCR assays. The human-specific Bacteroidales markers exhibited moderate correlation with conventional fecal indicators using RT-qPCR results, suggesting the persistence of nonhuman sources of fecal pollution or the presence of false-positive signals. In general, the results from this study suggest that RNA-based assays can increase the detection sensitivity of fecal bacteria in urban watersheds impacted with human fecal sources.

A streptavidin-SOG chimera for all-optical immunoassays.

Immunological detection has been developed into a sensitive and versatile technique and is based on two requisite elements: targeting antibodies and an indicator, usually in the form of horseradish peroxidase or alkaline phosphatase. The specificity and turnover rate of these enzymes provide an efficient means of signal amplification, but both require a stopping agent to prevent overdevelopment, which limits scalability to mechanized fluidic systems. As an alternative, we present a fully optical detection system based on a streptavidin-singlet oxygen generating chimeric protein that produces singlet oxygen from blue light. When used with trans-1-(2'-methoxyvinyl)pyrene, the photosynthetic streptavidin combines indicator development and reporting in sufficiently distinct visible wavelengths while retaining the sensitivity and scale of enzymatic systems that use horseradish peroxidase. By combining photosensitive development and detection into one system, we can enable future, highly parallel immunological testing to be controlled with the spatial and temporal precision of light.

Sequencing human mitochondrial hypervariable region II as a molecular fingerprint for environmental waters.

To protect environmental water from human fecal contamination, authorities must be able to unambiguously identify the source of the contamination. Current identification methods focus on tracking fecal bacteria associated with the human gut, but many of these bacterial indicators also thrive in the environment and in other mammalian hosts. Mitochondrial DNA could solve this problem by serving as a human-specific marker for fecal contamination. Here we show that the human mitochondrial hypervariable region II can function as a molecular fingerprint for human contamination in an urban watershed impacted by combined sewer overflows. We present high-throughput sequencing analysis of hypervariable region II for spatial resolution of the contaminated sites and assessment of the population diversity of the impacting regions. We propose that human mitochondrial DNA from public waste streams may serve as a tool for identifying waste sources definitively, analyzing population diversity, and conducting other anthropological investigations.

Human mitochondrial DNA and endogenous bacterial surrogates for risk assessment of graywater reuse.

Previous graywater risk assessment studies have focused on fecal contamination, yet the low density of fecal indicators may not provide the most useful approach to assess pathogen removal during graywater treatment. In this study, we employed high throughput bacterial sequencing and qPCR to elucidate potential microbial surrogates in wastewater sourced from an industrial laundry. In addition, we explored human mitochondrial DNA (HmtDNA) as a new, potentially more reliable molecular marker, because it can be unambiguously sourced, has a high copy number per cell, and is persistent when released from cells with no self-replication in graywater. Pyrosequencing and qPCR revealed that laundry water microbiota was dominated by the skin-associated bacteria Staphylococcus, Corynebacterium, and Propionibacterium (6.5, 5.7, 5.4 log10 copies/100 mL, respectively). While HmtDNA was less abundant (2.8 log10 copies/100 mL), it showed a strong positive correlation with the opportunistic pathogen Staphylococcus aureus (r=0.54, P=3.2×10(-4)) and closely followed a first-order exponential decay model (R2=0.98), remaining detectable in stored laundry graywater for up to 6 days at 20 °C. Based on abundance and persistence, we propose HmtDNA and total Staphylococcus as future laundry graywater treatment surrogates to potentially assess a wide dynamic range of pathogen removal.

Engineering bacterial efflux pumps for solar-powered bioremediation of surface waters.

Antibiotics are difficult to selectively remove from surface waters by present treatment methods. Bacterial efflux pumps have evolved the ability to discriminately expel antibiotics and other noxious agents via proton and ATP driven pathways. Here, we describe light-dependent removal of antibiotics by engineering the bacterial efflux pump AcrB into a proteovesicle system. We have created a chimeric protein with the requisite proton motive force by coupling AcrB to the light-driven proton pump Delta-rhodopsin (dR) via a glycophorin A transmembrane domain. This creates a solar powered protein material capable of selectively capturing antibiotics from bulk solutions. Using environmental water and direct sunlight, our AcrB-dR vesicles removed almost twice as much antibiotic as the treatment standard, activated carbon. Altogether, the AcrB-dR system provides an effective means of extracting antibiotics from surface waters as well as potential antibiotic recovery through vesicle solubilization.

Cardiac magnetic resonance imaging characterization of acute rejection in a porcine heterotopic heart transplantation model.

Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.

Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial.

AIMS: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection. METHODS AND RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group. CONCLUSION: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04883528.

Correlative assessment of fecal indicators using human mitochondrial DNA as a direct marker.

Identifying the source of surface water fecal contamination is paramount to mitigating pollution and risk to human health. Fecal bacteria such as E. coli have been staple indicator organisms for over a century, however there remains uncertainty with E. coli-based metrics since these bacteria are abundant in the environment. The relationships between the presence of direct indicator of human waste (human mitochondrial DNA), human-specific Bacteroidales, and E. coli were studied for water samples taken from an urban creek system (Duck Creek Watershed, Cincinnati, OH) impacted by combined sewer overflows. Logistic regression analysis shows that human-specific Bacteroidales correlates much more closely to human mitochondrial DNA (R = 0.62) relative to E. coli (R = 0.33). We also examine the speciation of Bacteroidales within the Duck Creek Watershed using next-generation sequencing technology (Ion Torrent) and show the most numerous populations to be associated with sewage. Here we demonstrate that human-specific Bacteroidales closely follow the dynamics of human mitochondrial DNA concentration changes, indicating that these obligate anaerobes are more accurate than E. coli for fecal source tracking, lending further support to risk overestimation using coliforms, especially fecal coliforms and E. coli.

Reference values of myocardial native T1 and extracellular volume in patients without structural heart disease and had negative 3T cardiac magnetic resonance adenosine stress test.

Background: To establish the reference values of native T1 and extracellular volume (ECV) in patients without structural heart disease and had a negative adenosine stress 3T cardiac magnetic resonance. Methods: Short-axis T1 mapping images were acquired using a modified Look-Locker inversion recovery technique before and after administration of 0.15 mmol/kg gadobutrol to calculate both native T1 and ECV. To compare the agreement between measurement strategies, regions of interest (ROI) were drawn in all 16 segments then averaged to represent mean global native T1. Additionally, an ROI was drawn in the mid-ventricular septum on the same image to represent the mid-ventricular septal native T1. Results: Fifty-one patients (mean 65 years, 65 % women) were included. Mean global native T1 averaged from all 16 segments and a mid-ventricular septal native T1 were not significantly different (1221.2 ± 35.2 vs 1228.4 ± 43.7 ms, p = 0.21). Men had lower mean global native T1 (1195 ± 29.8 vs 1235.5 ± 29.4 ms, p < 0.001) than women. Both mean global and mid-ventricular septal native T1 were not correlated with age (r = 0.21, p = 0.13 and r = 0.18, p = 0.19, respectively). The calculated ECV was 26.6 ± 2.7 %, which was not influenced by either gender or age. Conclusions: We report the first study to validate the native T1 and ECV reference ranges, factors influencing T1, and the validation across measurement methods in older Asian patients without structural heart disease and had a negative adenosine stress test. These references allow for better detection of abnormal myocardial tissue characteristics in clinical practice.