Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II-Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice.

BACKGROUND: Obesity increases the risk for human abdominal aortic aneurysms (AAAs) and enhances Ang II (angiotensin II)-induced AAA formation in C57BL/6J mice. Obesity is also associated with increases in perivascular fat that expresses proinflammatory markers including SAA (serum amyloid A). We previously reported that deficiency of SAA significantly reduces Ang II-induced inflammation and AAA in hyperlipidemic apoE-deficient mice. In this study. we investigated whether adipose tissue-derived SAA plays a role in Ang II-induced AAA in obese C57BL/6J mice. METHODS: The development of AAA was compared between male C57BL/6J mice (wild type), C57BL/6J mice lacking SAA1.1, SAA2.1, and SAA3 (TKO); and TKO mice harboring a doxycycline-inducible, adipocyte-specific SAA1.1 transgene (TKO-Tgfat; SAA expressed only in fat). All mice were fed an obesogenic diet and doxycycline to induce SAA transgene expression and infused with Ang II to induce AAA. RESULTS: In response to Ang II infusion, SAA expression was significantly increased in perivascular fat of obese C57BL/6J mice. Maximal luminal diameters of the abdominal aorta were determined by ultrasound before and after Ang II infusion, which indicated a significant increase in aortic luminal diameters in wild type and TKO-TGfat mice but not in TKO mice. Adipocyte-specific SAA expression was associated with MMP (matrix metalloproteinase) activity and macrophage infiltration in abdominal aortas of Ang II-infused obese mice. CONCLUSIONS: We demonstrate for the first time that SAA deficiency protects obese C57BL/6J mice from Ang II-induced AAA. SAA expression only in adipocytes is sufficient to cause AAA in obese mice infused with Ang II.

Highlights of the Virtual Society for Cardiovascular Magnetic Resonance 2022 Scientific Conference: CMR: improving cardiovascular care around the world.

The 25th Society for Cardiovascular Magnetic Resonance (SCMR) Annual Scientific Sessions saw 1524 registered participants from more than 50 countries attending the meeting virtually. Supporting the theme "CMR: Improving Cardiovascular Care Around the World", the meeting included 179 invited talks, 52 sessions including 3 plenary sessions, 2 keynote talks, and a total of 93 cases and 416 posters. The sessions were designed so as to showcase the multifaceted role of cardiovascular magnetic resonance (CMR) in identifying and prognosticating various myocardial pathologies. Additionally, various social networking sessions as well as fun activities were organized. The major areas of focus for the future are likely to be rapid efficient and high value CMR exams, automated and quantitative acquisition and post-processing using artificial intelligence and machine learning, multi-contrast imaging and advanced vascular imaging including 4D flow.

T1 mapping performance and measurement repeatability: results from the multi-national T1 mapping standardization phantom program (T1MES).

BACKGROUND: The T1 Mapping and Extracellular volume (ECV) Standardization (T1MES) program explored T1 mapping quality assurance using a purpose-developed phantom with Food and Drug Administration (FDA) and Conformité Européenne (CE) regulatory clearance. We report T1 measurement repeatability across centers describing sequence, magnet, and vendor performance. METHODS: Phantoms batch-manufactured in August 2015 underwent 2 years of structural imaging, B0 and B1, and "reference" slow T1 testing. Temperature dependency was evaluated by the United States National Institute of Standards and Technology and by the German Physikalisch-Technische Bundesanstalt. Center-specific T1 mapping repeatability (maximum one scan per week to minimum one per quarter year) was assessed over mean 358 (maximum 1161) days on 34 1.5 T and 22 3 T magnets using multiple T1 mapping sequences. Image and temperature data were analyzed semi-automatically. Repeatability of serial T1 was evaluated in terms of coefficient of variation (CoV), and linear mixed models were constructed to study the interplay of some of the known sources of T1 variation. RESULTS: Over 2 years, phantom gel integrity remained intact (no rips/tears), B0 and B1 homogenous, and "reference" T1 stable compared to baseline (% change at 1.5 T, 1.95 ± 1.39%; 3 T, 2.22 ± 1.44%). Per degrees Celsius, 1.5 T, T1 (MOLLI 5s(3s)3s) increased by 11.4 ms in long native blood tubes and decreased by 1.2 ms in short post-contrast myocardium tubes. Agreement of estimated T1 times with "reference" T1 was similar across Siemens and Philips CMR systems at both field strengths (adjusted R2 ranges for both field strengths, 0.99-1.00). Over 1 year, many 1.5 T and 3 T sequences/magnets were repeatable with mean CoVs < 1 and 2% respectively. Repeatability was narrower for 1.5 T over 3 T. Within T1MES repeatability for native T1 was narrow for several sequences, for example, at 1.5 T, Siemens MOLLI 5s(3s)3s prototype number 448B (mean CoV = 0.27%) and Philips modified Look-Locker inversion recovery (MOLLI) 3s(3s)5s (CoV 0.54%), and at 3 T, Philips MOLLI 3b(3s)5b (CoV 0.33%) and Siemens shortened MOLLI (ShMOLLI) prototype 780C (CoV 0.69%). After adjusting for temperature and field strength, it was found that the T1 mapping sequence and scanner software version (both P < 0.001 at 1.5 T and 3 T), and to a lesser extent the scanner model (P = 0.011, 1.5 T only), had the greatest influence on T1 across multiple centers. CONCLUSION: The T1MES CE/FDA approved phantom is a robust quality assurance device. In a multi-center setting, T1 mapping had performance differences between field strengths, sequences, scanner software versions, and manufacturers. However, several specific combinations of field strength, sequence, and scanner are highly repeatable, and thus, have potential to provide standardized assessment of T1 times for clinical use, although temperature correction is required for native T1 tubes at least.

Incidental Coronary Artery Calcification and Stroke Risk in Patients With Atrial Fibrillation.

OBJECTIVE. Atrial fibrillation (AF) is a major risk factor for stroke. The CHA2DS2-VASc score is used to risk stratify patients, and the score includes known coronary artery disease (CAD) as a variable. The aim of this study was to assess if the presence of incidental coronary artery calcification (CAC), without known CAD, is associated with stroke independent of CHA2DS2-VASc variables. MATERIALS AND METHODS. A retrospective review of health records was performed for patients who had AF, a chest CT scan performed within 1 year, and a subsequent visit for stroke. Patients with CAD and other vascular disease, a mechanical valve, or who were older than 74 years old were excluded. Included patients were one-to-one matched by age and CHA2DS2-VASc risk factors to patients who had had similar follow-up but who did not have a stroke. Nongated CT images were reviewed for CAC. Univariate and Cox regression analyses were performed. RESULTS. A total of 203 patients met the study criteria, and 203 matched patients without stroke were identified. Median age was 61 years old with stroke and 62 years old without stroke (p = 0.99). In both groups, 82 (39.0%) were women and the median CHA2DS2-VASc was 2 (interquartile range, 1-2). Anticoagulation medication was prescribed to 46 (22.7%) patients in the group who had had a stroke and 52 (25.6%) in the group without stroke (p = 0.49). On Cox regression analysis, CAC was associated with stroke (hazard ratio [HR], 1.47; 95% CI, 1.10-1.97; p < 0.01) and mortality (adjusted HR, 1.41; 95% CI, 1.02-1.95; p = 0.04). CONCLUSION. Patients with AF and incidental CAC depicted on chest CT have an increased risk of stroke and mortality beyond established risk factors.

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function.

Systolic cardiac function is typically preserved in obese adults, potentially masking underlying declines in cardiomyocyte metabolism that may contribute to heart failure. We used chemical exchange saturation transfer (CEST) MRI, a sensitive method for measurement of myocardial creatine, to examine whether myocardial creatine levels correlate with cardiac structure, contractile function, or visceral fat mass in obese adults. In this study, obese (body mass index, BMI > 30, n = 20) and healthy (BMI < 25, n = 11) adults were examined with dual-energy x-ray absorptiometry to quantify fat masses. Cine MRI and myocardial tagging were performed at 1.5 T to measure ventricular structure and global function. CEST imaging with offsets in the range of ±10 parts per million (ppm) were performed in one mid-ventricular slice, where creatine CEST contrast was calculated at 1.8 ppm following field homogeneity correction. Ventricular structure, global function (ejection fraction 69.4 ± 4.3% healthy versus 69.6 ± 9.3% obese, NS), and circumferential strain (-17.0 ± 2.3% healthy versus -16.5 ± 1.5% obese, NS) and strain rate were preserved in obese adults. However, creatine CEST contrast was significantly reduced in obese adults (6.8 ± 1.3% healthy versus 4.1 ± 2.7% obese, p = 0.001). Creatine CEST contrast was inversely correlated with total body fat% (ρ = -0.45, p = 0.011), visceral fat mass (ρ = -0.58, p = 0.001), and septal wall thickness (ρ = -0.44, p = 0.013), but uncorrelated to ventricular function or contractile function. In conclusion, creatine CEST-MRI reveals a strong correlation between heightened body and visceral fat masses and reduced myocardial metabolic function that is independent of ventricular structure and global function in obese adults.

Atrioventricular dyssynchrony from empiric device settings is common in cardiac resynchronization therapy and adversely impacts left ventricular morphology and function.

BACKGROUND: Echocardiographic atrioventricular (AV) optimization after cardiac resynchronization therapy (CRT) is uncommon due to time constraints and the use of vendor-specific device algorithms. It remains unclear whether optimization of mitral inflow velocities can still be useful. We aimed to investigate post implantation left ventricular (LV) inflow patterns to determine the incidence of AV dyssynchrony from empirically set devices. METHODS: This was a retrospective study of patients undergoing CRT using empiric device settings. Forty-eight patients with clinical, echocardiographic, and pacemaker follow-up were grouped by their post implantation LV filling pattern. Baseline characteristics and echocardiographic measurements were compared with post implantation findings at median 6.3 months (interquartile range [IQR], 3.9-17.0). RESULTS: Twenty-four patients demonstrated AV dyssynchrony (Group 1) after CRT, and 24 patients did not (Group 2). Group 1 patients had less LV reverse remodeling compared to Group 2 patients (ΔLV end-diastolic volume: -3.6 mL vs -49.5 mL, P<.05; ΔLV end-systolic volume: -16.9 mL vs -53.5 mL, P<.05) and did not experience significant improvements in LV outflow tract velocity time integral, stroke volume, or LV ejection fraction. There were no differences in new-onset atrial fibrillation, heart failure readmissions, or mortality between groups. CONCLUSION: Our study suggests that up to 50% of patients with empiric device settings have AV dyssynchrony at 6 months despite atrioventricular delay optimization (AVO) algorithms. As AV dyssynchrony is common and has proven to be modifiable, a strategic approach to Doppler echocardiography-guided AVO after CRT is warranted, particularly in nonresponders where the LV filling pattern is fused or truncated.

Gadolinium free cardiovascular magnetic resonance with 2-point Cine balanced steady state free precession.

BACKGROUND: Cardiovascular magnetic resonance (CMR) of ventricular structure and function is widely performed using cine balanced steady state free precession (bSSFP) MRI. The bSSFP signal of myocardium is weighted by magnetization transfer (MT) and T1/T2-relaxation times. In edematous and fibrotic tissues, increased T2 and reduced MT lead to increased signal intensity on images acquired with high excitation flip angles. We hypothesized that acquisition of two differentially MT-weighted bSSFP images (termed 2-point bSSFP) can identify tissue that would enhance with gadolinium similar to standard of care late gadolinium enhancement (LGE). METHODS: Cine bSSFP images (flip angles of 5° and 45°) and native-T1 and T2 maps were acquired in one mid-ventricular slice in 47 patients referred for CMR and 10 healthy controls. Afterwards, LGE images and post-contrast T1 maps were acquired and gadolinium partition coefficient (GPC) was calculated. Maps of ΔS/So were calculated as (S45-S5)/S5*100 (%), where Sflip_angle is the voxel signal intensity. RESULTS: Twenty three patients demonstrated areas of myocardial hyper-enhancement with LGE. In enhanced regions, ΔS/So, native-T1, T2, and GPC were heightened (p < 0.05 vs. non-enhanced tissues). ΔS/So, native-T1, and T2 all demonstrated association with GPC, however the association was strongest for ΔS/So. Bland-Altman analysis revealed a slight bias towards larger volume of enhancement with ΔS/So compared to LGE, and similar transmurality. Subjective analysis with 2-blinded expert readers revealed agreement between ΔS/So and LGE of 73.4 %, with false positive detection of 16.7 % and false negative detection of 15.2 %. CONCLUSIONS: Gadolinium free 2-point bSSFP identified tissue that enhances at LGE with strong association to GPC. Our results suggest that with further development, MT-weighted CMR could be used similar to LGE for diagnostic imaging.

QRS duration predicts death and hospitalization among patients with atrial fibrillation irrespective of heart failure: evidence from the AFFIRM study.

AIMS: The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF. METHODS AND RESULTS: QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90-119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29-2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07-1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90-119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90-119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14). CONCLUSION: Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF.

Simplified echocardiographic assessment of regional left ventricular wall motion pattern in patients with takotsubo and acute coronary syndrome: The Randomized Blinded Two-chamber Apical Kinesis Observation (TAKO) Study.

BACKGROUND: Differentiating Takotsubo cardiomyopathy (TTC) from acute coronary syndrome involving the left anterior descending coronary artery (LAD-ACS) is difficult due to left ventricular apical wall motion abnormality pattern in both and typically requires an invasive coronary angiography (ICA) study for diagnostic confirmation. OBJECTIVES: To identify differences in the regional wall motion abnormality (RWMA) pattern using a comprehensive comparative analysis of the transthoracic echocardiographic (TTE) findings in patients with TTC versus LAD-ACS. METHODS: This was a retrospective, randomized, blinded comparison study including a derivation cohort of 105 patients with TTC (N=52) or LAD-ACS (N=53) with concomitant TTE and ICA identified from our institutional database. A comprehensive echocardiographic wall motion analysis was performed (unblinded) to search for subtle differences in RWMA patterns by marking the exact locations of the end-systolic hinge points (HP) - defined as the intersection between the normal and abnormal regional myocardial thickening - in all apical views. The HP location relative to mitral annulus in each apical view was compared for symmetry and the apical 2-chamber (A2C) view was identified as having the most consistent, quantitative difference between TTC and LAD-ACS. This A2C quantitative model was then prospectively studied in a randomized, blinded, validation cohort of 30 subjects with either TTC or LAD-ACS by eight echocardiographic readers with all levels of clinical experience. RESULTS: In the unblinded derivation cohort, the A2C view showed that the ratio (1.02) and the absolute distance between the anterior HP (3.57 cm) and the inferior HP (3.53 cm) in TTC was significantly different than the ratio (0.761) and the absolute differences between the AHP (4.5 cm) and the IHP (5.93 cm) in LAD-ACS. An AHP: IHP of 0.96 for men and 0.84 for women was able to correctly categorize 84.8% of male and 91.7% of female patients. When applied to the validation cohort, the model showed fairly accurate results with a 74% prediction rate in diagnosing TTC in female patients. CONCLUSION: We propose a relatively simple 2-D TTE diagnostic tool emphasizing subtle differences in the RWMA pattern in the A2C view alone as a semi-quantitative imaging parameter to help differentiate TTC from LAD-ACS.

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

OBJECTIVE: We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. METHODS: Eight male patients (age 62 ± 2.4 years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. RESULTS: No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6 months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. CONCLUSIONS: Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.

The Evolving Trends in Infective Endocarditis and Determinants of Mortality: a 10-year Experience From a Tertiary Care Epicenter.

The epidemiology of infective endocarditis (IE) continues to evolve in areas affected by the opioid epidemic. Understanding the demographics of the disease allows us to better tailor therapy towards this at-risk population. This was an observational study of adults (age ≥ 18) admitted to the University of Kentucky hospital with IE between January 2009 and December 2018. 1,255 patients were included in the final analysis. The mean age was 42 years, 45% were female and injection drug use was seen in 66% of patients. On multivariable analysis, higher Charlson comorbidity indices, left sided, and multivalve involvement were associated with increased mortality, whereas surgical intervention demonstrated a trend towards lower mortality. Our results highlight the alarming increase in injection drug use related IE and the high mortality rates despite therapeutic advances. Patients with left sided IE, multivalve involvement and a higher Charlson comorbidity index had decreased survival.

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations. OBJECTIVES: In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD. METHODS: Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting. RESULTS: SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality. CONCLUSIONS: Stress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).

MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study.

BACKGROUND: Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI. METHODS: Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis. RESULTS: Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI's; LGE had two false positive MI's including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001). CONCLUSION: While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI's than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.

Reproducibility of Systolic Strain in Mice Using Cardiac Magnetic Resonance Feature Tracking of Black-Blood Cine Images.

PURPOSE: Mouse models are widely utilized to enhance our understanding of cardiac disease. The goal of this study is to investigate the reproducibility of strain parameters that were measured in mice using cardiac magnetic resonance (CMR) feature-tracking (CMR42, Canada). METHODS: We retrospectively analyzed black-blood CMR datasets from thirteen C57BL/6 B6.SJL-CD45.1 mice (N = 10 female, N = 3 male) that were imaged previously. The circumferential, longitudinal, and radial (Ecc, Ell, and Err, respectively) parameters of strain were measured in the mid-ventricular region of the left ventricle. Intraobserver and interobserver reproducibility were assessed for both the end-systolic (ES) and peak strain. RESULTS: The ES strain had larger intraclass correlation coefficient (ICC) values when compared to peak strain, for both the intraobserver and interobserver reproducibility studies. Specifically, the intraobserver study showed excellent reproducibility for all three ES strain parameters, namely, Ecc (ICC 0.95, 95% CI 0.83-0.98), Ell (ICC 0.90, 95% CI 0.59-0.97), and Err (ICC 0.92, 95% CI 0.73-0.97). This was also the case for the interobserver study, namely, Ecc (ICC 0.92, 95% CI 0.60-0.98), Ell (ICC 0.76, 95% CI 0.33-0.93), and Err (ICC 0.93, 95% CI 0.68-0.98). Additionally, the coefficient of variation values were all < 10%. CONCLUSION: The results of this preliminary study showed excellent reproducibility for all ES strain parameters, with good to excellent reproducibility for the peak strain parameters. Moreover, all ES strain parameters had larger ICC values than the peak strain. In general, these results imply that feature-tracking with CMR42 software and black-blood cine images can be reliably used to assess strain patterns in mice.

Prognostic Value of Stress Cardiac Magnetic Resonance in Patients With Known Coronary Artery Disease.

OBJECTIVES: This study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States. BACKGROUND: Despite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing. METHODS: From the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined. RESULTS: Out of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P < 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P < 0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P < 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively. CONCLUSIONS: In a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a <2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions.

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 ± 0.34% (value is the mean ± S.D.) increased Hct to 28.3 ± 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P.

ST-Segment Elevation in a Patient With Nausea, Vomiting, and Intracerebral Hemorrhage.

A 60-year-old man who presented with nausea, vomiting, and intracerebral hemorrhage developed inferior ST-segment elevation and angina. Coronary angiography showed no coronary obstruction. The patient was found to have a small bowel obstruction causing superior translocation of the heart. Relief of obstruction caused immediate resolution of electrocardiographic changes and symptoms. (Level of Difficulty: Beginner.).