[Study of Rapid HPLC Method for the Determination of Antioxidants in Foods, and Standard Solution Stability during Storage].

In this study, we simultaneously determined three antioxidants, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and tert-butylhydroquinone (TBHQ), using HPLC equipped both with a photodiode array detector and a fluorescence detector in 25 minutes per sample. Due to the combined use of the two detectors, we could achieve improved target selectivity. Further, quantification at the specific wavelengths for each target substance particularly increased BHT detection sensitivity. This approach enabled us to avoid repeated measurements during daily inspections. Furthermore, detections were performed using LC-MS/MS instead of GC-MS to overcome the problem of helium gas shortage.In addition, we investigated antioxidant stability in standard solutions during storage. Although TBHQ was stable in methanol with ascorbic acid at -20℃, ascorbic acid storage has possibility to lead to decrease in BHT and BHA concentrations. We recognized that the mixture of BHT and BHA dissolved in methanol at 4℃ and that of BHT, BHA and TBHQ dissolved in methanol with ascorbic acid at -20℃ were suitable for about one year.

Right ventricular insertion site fibrosis in a dilated cardiomyopathy referral population: phenotypic associations and value for the prediction of heart failure admission or death.

BACKGROUND: Dilated cardiomyopathy (DCM) is increasingly recognized as a heterogenous disease with distinct phenotypes on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. While mid-wall striae (MWS) fibrosis is a widely recognized phenotypic risk marker, other fibrosis patterns are prevalent but poorly defined. Right ventricular (RV) insertion (RVI) site fibrosis is commonly seen, but without objective criteria has been considered a non-specific finding. In this study we developed objective criteria for RVI fibrosis and studied its clinical relevance in a large cohort of patients with DCM. METHODS: We prospectively enrolled 645 DCM patients referred for LGE-CMR. All underwent standardized imaging protocols and baseline health evaluations. LGE images were blindly scored using objective criteria, inclusive of RVI site and MWS fibrosis. Associations between LGE patterns and CMR-based markers of adverse chamber remodeling were evaluated. Independent associations of LGE fibrosis patterns with the primary composite clinical outcome of heart failure admission or death were determined by multivariable analysis. RESULTS: The mean age was 56 ± 14 (28% female) with a mean left ventricular (LV) ejection fraction (LVEF) of 37%. At a median of 1061 days, 129 patients (20%) experienced the primary outcome. Any abnormal LGE was present in 306 patients (47%), inclusive of 274 (42%) meeting criteria for RVI site fibrosis and 167 (26%) for MWS fibrosis. All with MWS fibrosis showed RVI site fibrosis. Solitary RVI site fibrosis was associated with higher bi-ventricular volumes [LV end-systolic volume index (78 ± 39 vs. 66 ± 33 ml/m2, p = 0.01), RV end-diastolic volume index (94 ± 28 vs. 84 ± 22 ml/m2 (p < 0.01), RV end-systolic volume index (56 ± 26 vs. 45 ± 17 ml/m2, p < 0.01)], lower bi-ventricular function [LVEF 35 ± 12 vs. 39 ± 10% (p < 0.01), RV ejection fraction (RVEF) 43 ± 12 vs. 48 ± 10% (p < 0.01)], and higher extracellular volume (ECV). Patient with solitary RVI site fibrosis experienced a non-significant 1.4-fold risk of the primary outcome, increasing to a significant 2.6-fold risk when accompanied by MWS fibrosis. CONCLUSIONS: RVI site fibrosis in the absence of MWS fibrosis is associated with bi-ventricular remodelling and intermediate risk of heart failure admission or death. Our study findings suggest RVI site fibrosis to be pre-requisite for the incremental development of MWS fibrosis, a more advanced phenotype associated with greater LV remodeling and risk of clinical events.

Browning of Maillard reaction systems containing xylose and 4-hydroxy-5-methyl-3(2H)-furanone.

Pentose is involved in the browning through the Maillard reaction of food derived of plant origin. During research on the Maillard reaction between xylose (Xyl) and lysine (Lys), we detected 4-hydroxy-5-methyl-3(2H)-furanone (HMFO) as a major decomposition product of Xyl. To clarify the chemical pathway of the browning of pentose system, the formation and decomposition of dicarbonyls from HMFO and Xyl were examined. In the HMFO system, HMFO was oxidatively hydrolyzed to form 2-hydroxy-3,4-dioxopentanal, which leads to the formation of methylglyoxal (MGO) and then diacetyl (DA). In the Xyl system, MGO was also the major dicarbonyl degradation product from 1-deoxyxylosone (1-DX). Among Xyl, HMFO, MGO, and DA, MGO turned brown most rapidly in the presence of Lys and formed melanoidin-like brown pigments. In the Xyl system, MGO derived from HMFO and 1-DX most contributed to the browning, although some low-molecular-weight pigments, a colorless polymer, and fluorescent substances were also formed.

Layer-specific strain in patients with heart failure using cardiovascular magnetic resonance: not all layers are the same.

BACKGROUND: Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. METHODS: Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. RESULTS: GLS_EPI distinguished all groups with preserved LVEF (controls - 16.5 ± 2.4% vs. at-risk - 15.5 ± 2.7% vs. HFpEF - 14.1 ± 3.0%, p < 0.001) while GLS_ENDO and all GCS (all layers) were similar among these groups. GRS was reduced in HFpEF (41.1 ± 13.8% versus 48.9 ± 10.7% in controls, p < 0.001) and the difference between GLS_EPI and GLS_ENDO were significantly larger in HFpEF as compared to controls. Within the preserved LVEF groups, reduced GRS and GLS_EPI were significantly associated with increased LV mass (LVM) and LVM/LV end-diastolic volume EDV (concentricity). In multivariable analysis, only GLS_AVE and GRS predicted 5-year all-cause mortality (all ps < 0.05), with the strongest association with 5-year all-cause mortality by Akaike Information Criterion analysis and significant incremental value for outcomes prediction beyond LVEF or GLS_ENDO by the likelihood ratio test. CONCLUSION: Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Effects of age, gender, and risk-factors for heart failure on native myocardial T1 and extracellular volume fraction using the SASHA sequence at 1.5T.

BACKGROUND: Understanding cardiac MR T1 mapping values might require examination of the effects of age, gender, and heart failure risk factors. PURPOSE/HYPOTHESIS: To evaluate the effects of gender, age, and presence of heart failure risk factors on myocardial native T1 and extracellular volume fraction (ECV). STUDY TYPE: Retrospective, cross-sectional, observational study. POPULATION: Secondary analysis of cardiac MR data, separated by gender and health status, based on the presence of at least one heart failure risk factor. FIELD STRENGTH/SEQUENCE: Cardiac MR imaging at 1.5T, including T1 mapping using the SAturation recovery single-SHot Acquisition (SASHA) sequence. ASSESSMENT: Interventricular septal region-of-interest analysis for assessment of native T1 and ECV. STATISTICAL TESTS: Group comparisons performed using Student t-test, or nonparametric equivalent. Linear regression was used to assess relationships between age and T1 measurements. RESULTS: Native T1 and ECV were available in 187 and 143 subjects, respectively. T1 and ECV were independent of age in all groups (Native T1 : healthy women P = 0.655; healthy men P = 0.906; at-risk women P = 0.487; at-risk men P = 0.683; ECV: healthy women P = 0.685; healthy men P = 0.199; at-risk women P = 0.152; at-risk men P = 0.747). T1 and ECV were higher in healthy women versus men (1202 ± 30 ms versus 1167 ± 36 ms, P = 0.0000 and 22 ± 2% versus 20 ± 2%, P = 0.0089), while values were similar in women and men with risk factors (1197 ± 55 ms versus 1193 ± 45 ms, P = 0.6556, 21 ± 2% versus 21 ± 3%, P = 0.5039). No differences existed in native T1 or ECV between women with or without risk factors (P = 0.6344 and P = 0.1026), whereas men with risk factors showed higher native T1 values (P = 0.0070). DATA CONCLUSION: Native T1 and ECV measured with SASHA do not vary with age, regardless of gender or the presence of factors for heart failure. Native T1 and ECV are higher in healthy women than men, but do not differ in the presence of risk factors, suggesting a different myocardial response to risk factors between genders. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1307-1317.

Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM. METHODS: Seventy-six HCM patients (51 male, age 54 ± 13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed. RESULTS: Fifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC = 0.97, mean difference and 95% limits of agreement = 1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC = 0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively. CONCLUSIONS: FWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Sex-based differences in the phenotypic expression and prognosis of idiopathic non-ischaemic cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. CONCLUSION: In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

No cardioprotective benefit of ischemic postconditioning in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Postconditioning is a potential cardioprotective strategy that has demonstrated conflicting and variable reductions in infarct size in human trials. OBJECTIVES: To determine whether postconditioning could increase the extent of myocardial salvage in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). METHODS: One hundred two patients (aged 57 ± 11 years; 88% male) were randomly assigned to a postconditioning or standard protocol. Cardiovascular magnetic resonance imaging was performed 3 days after PPCI to measure the volumetric extent of myocardial necrosis and the area at risk. RESULTS: With similar time-to-reperfusion (170 ± 84 minutes in the postconditioning group vs. 150 ± 70 minutes in the standard group, P = 0.22), the myocardial salvage index was not significantly different between the postconditioned group and the control group, averaging 42 ± 22% vs. 33 ± 21%, respectively (P = 0.08). Furthermore, postconditioning was not associated with a smaller infarct size compared to controls (13 ± 7 g/m(2) vs. 15 ± 8 g/m(2), respectively, P = 0.18). CONCLUSIONS: Postconditioning does not significantly increase myocardial salvage or reduce infarct size in patients with STEMI undergoing PPCI. However, the possibility of a more modest impact of postconditioning cannot be excluded with our sample size.

Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo.

Side population (SP) cells, which can be identified by their ability to exclude Hoechst 33342 dye, are one of the candidates for somatic stem cells. Although bone marrow SP cells are known to be long-term repopulating hematopoietic stem cells, there is little information about the characteristics of cardiac SP cells (CSPs). When cultured CSPs from neonatal rat hearts were treated with oxytocin or trichostatin A, some CSPs expressed cardiac-specific genes and proteins and showed spontaneous beating. When green fluorescent protein-positive CSPs were intravenously infused into adult rats, many more ( approximately 12-fold) CSPs were migrated and homed in injured heart than in normal heart. CSPs in injured heart differentiated into cardiomyocytes, endothelial cells, or smooth muscle cells (4.4%, 6.7%, and 29% of total CSP-derived cells, respectively). These results suggest that CSPs are intrinsic cardiac stem cells and involved in the regeneration of diseased hearts.

[Influence of pre-analytical storage conditions on four plasma coagulation molecular markers measured using a STACIA automatic coagulation analyzer].

We investigated the effects of specimen storage conditions on the analysis of the coagulation molecular markers, soluble fibrin (SF), thrombin-antithrombin complex (TAT), thrombomodulin (TM) and tissue plasminogen activator inhibitor-1 complex (total PAI-1: tPAI). Marker levels were measured using a STACIA automatic coagulation analyzer. Among these four markers in blood from healthy subjects, only tPAI increased gradually with time, and the differences were especially marked when blood samples were stored at room temperature. Patient blood samples were stored for 4 hours under three different conditions: whole blood storage on ice, storage on ice after centrifugation, and refrigerated storage after centrifugation. Analytical results were compared between the three sets of samples. There were no significant differences in TAT or TM after 4 hours' storage under the different conditions. However, SF was decreased in several samples. In 11 of 14 samples with >20 microg/ml SF, SF levels were reduced by >10 microg/ml when whole blood without centrifugation was stored on ice. tPAI levels increased slightly after storage for 4 hours under all three conditions. These results suggest that centrifugation followed by refrigeration is the optimal storage method for blood samples when all four markers are to be measured simultaneously in the same sample.

Machine Learning Patient-Specific Prediction of Heart Failure Hospitalization Using Cardiac MRI-Based Phenotype and Electronic Health Information.

Background: Heart failure (HF) hospitalization is a dominant contributor of morbidity and healthcare expenditures in patients with systolic HF. Cardiovascular magnetic resonance (CMR) imaging is increasingly employed for the evaluation of HF given capacity to provide highly reproducible phenotypic markers of disease. The combined value of CMR phenotypic markers and patient health information to deliver predictions of future HF events has not been explored. We sought to develop and validate a novel risk model for the patient-specific prediction of time to HF hospitalization using routinely reported CMR variables, patient-reported health status, and electronic health information. Methods: Standardized data capture was performed for 1,775 consecutive patients with chronic systolic HF referred for CMR imaging. Patient demographics, symptoms, Health-related Quality of Life, pharmacy, and routinely reported CMR features were provided to both machine learning (ML) and competing risk Fine-Gray-based models (FGM) for the prediction of time to HF hospitalization. Results: The mean age was 59 years with a mean LVEF of 36 ± 11%. The population was evenly distributed between ischemic (52%) and idiopathic non-ischemic cardiomyopathy (48%). Over a median follow-up of 2.79 years (IQR: 1.59-4.04) 333 patients (19%) experienced HF related hospitalization. Both ML and competing risk FGM based models achieved robust performance for the prediction of time to HF hospitalization. Respective 90-day, 1 and 2-year AUC values were 0.87, 0.83, and 0.80 for the ML model, and 0.89, 0.84, and 0.80 for the competing risk FGM-based model in a holdout validation cohort. Patients classified as high-risk by the ML model experienced a 34-fold higher occurrence of HF hospitalization at 90 days vs. the low-risk group. Conclusion: In this study we demonstrated capacity for routinely reported CMR phenotypic markers and patient health information to be combined for the delivery of patient-specific predictions of time to HF hospitalization. This work supports an evolving migration toward multi-domain data collection for the delivery of personalized risk prediction at time of diagnostic imaging.

Influence of Sex-Based Differences in Cardiac Phenotype on Atrial Fibrillation Recurrence in Patients Undergoing Pulmonary Vein Isolation.

Background: Pulmonary vein isolation (PVI) is a commonly engaged therapy for symptomatic atrial fibrillation (AF). Prior studies have documented elevated AF recurrence rates among females vs. males. Sex-specific mechanisms underlying this phenomenon are poorly understood. This prospective cohort study aimed to evaluate the sex-based differences in cardiac phenotype and their influence on (AF) recurrence following first-time PVI. Methods: A total of 204 consecutive patients referred for first-time PVI and 101 healthy subjects were prospectively studied by cardiovascular magnetic resonance (CMR) imaging. Multi-chamber volumetric and functional measures were assessed by sex-corrected Z-score analyses vs. healthy subjects. Patients were followed for a median of 2.6 years for the primary outcome of clinical AF recurrence. Multivariable analyses adjusting for age and comorbidities were performed to identify independent predictors of AF recurrence. Results: AF recurrence following first PVI occurred in 41% of males and 59% of females (p = 0.03). Females were older with higher prevalence of hypertension and thyroid disorders. Z-score-based analyses revealed significantly reduced ventricular volumes, greater left atrial (LA) volumes, and reduced LA contractility in females vs. males. Multivariable analysis revealed each of LA minimum and pre-systolic volumes and booster EF Z-scores to be independently associated with AF recurrence, providing respective hazard ratios of 1.10, 1.19, and 0.89 (p = 0.001, 0.03, and 0.01). Conclusion: Among patients referred for first time PVI, females were older and demonstrated significantly poorer LA contractile health vs. males, the latter independently associated with AF recurrence. Assessment of LA contractile health may therefore be of value to identify female patients at elevated risk of AF recurrence. Factors influencing female patient referral for PVI at more advanced stages of atrial disease warrant focused investigation.

Mid-wall striae fibrosis predicts heart failure admission, composite heart failure events, and life-threatening arrhythmias in dilated cardiomyopathy.

Heart failure (HF) admission is a dominant contributor to morbidity and healthcare costs in dilated cardiomyopathy (DCM). Mid-wall striae (MWS) fibrosis by late gadolinium enhancement (LGE) imaging has been associated with elevated arrhythmia risk. However, its capacity to predict HF-specific outcomes is poorly defined. We investigated its role to predict HF admission and relevant secondary outcomes in a large cohort of DCM patients. 719 patients referred for LGE MRI assessment of DCM were enrolled and followed for clinical events. Standardized image analyses and interpretations were conducted inclusive of coding the presence and patterns of fibrosis observed by LGE imaging. The primary clinical outcome was hospital admission for decompensated HF. Secondary heart failure and arrhythmic composite endpoints were also studied. Median age was 57 (IQR 47-65) years and median LVEF 40% (IQR 29-47%). Any fibrosis was observed in 228 patients (32%) with MWS fibrosis pattern present in 178 (25%). At a median follow up of 1044 days, 104 (15%) patients experienced the primary outcome, and 127 (18%) the secondary outcome. MWS was associated with a 2.14-fold risk of the primary outcome, 2.15-fold risk of the secondary HF outcome, and 2.23-fold risk of the secondary arrhythmic outcome. Multivariable analysis adjusting for all relevant covariates, inclusive of LVEF, showed patients with MWS fibrosis to experience a 1.65-fold increased risk (95% CI 1.11-2.47) of HF admission and 1-year event rate of 12% versus 7% without this phenotypic marker. Similar findings were observed for the secondary outcomes. Patients with LVEF > 35% plus MWS fibrosis experienced similar event rates to those with LVEF ≤ 35%. MWS fibrosis is a powerful and independent predictor of clinical outcomes in patients with DCM, identifying patients with LVEF > 35% who experience similar event rates to those with LVEF below this conventionally employed high-risk phenotype threshold.

Machine learning prediction of atrial fibrillation in cardiovascular patients using cardiac magnetic resonance and electronic health information.

Background: Atrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning. Methods: Nine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC). Results: A RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients. Conclusions: Using phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

Cardiac remodelling predicts outcome in patients with chronic heart failure.

AIMS: Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. METHODS AND RESULTS: A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow-up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan-Meier analyses compared to those with no remodelling, log-rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. CONCLUSIONS: Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long-term outcomes whereas change in left ventricular ejection fraction did not.

Right Ventricular Ejection Fraction for the Prediction of Major Adverse Cardiovascular and Heart Failure-Related Events: A Cardiac MRI Based Study of 7131 Patients With Known or Suspected Cardiovascular Disease.

BACKGROUND: There is increasing evidence that right ventricular ejection fraction (RVEF) may provide incremental value to left ventricular (LV) ejection fraction for the prediction of major adverse cardiovascular events. To date, generalizable utility for RVEF quantification in patients with cardiovascular disease has not been established. Using a large prospective clinical outcomes registry, we investigated the prognostic value of RVEF for the prediction of major adverse cardiovascular events- and heart failure-related outcomes. METHODS: Seven thousand one hundred thirty-one consecutive patients with known or suspected cardiovascular disease undergoing cardiovascular magnetic resonance imaging were prospectively enrolled. Multichamber volumetric quantification was performed by standardized operational procedures. Patients were followed for the primary composite outcome of all-cause death, survived cardiac arrest, admission for heart failure, need for transplantation or LV assist device, acute coronary syndrome, need for revascularization, stroke, or transient ischemic attack. A secondary, heart failure focused outcome of heart failure admission, need for transplantation/LV assist device or death was also studied. RESULTS: Mean age was 54±15 years. The mean LV ejection fraction was 55±14% (range 6%-90%) with a mean RVEF of 54±10% (range 9%-87%). At a median follow-up of 908 days, 870 (12%) patients experienced the primary composite outcome and 524 (7%) the secondary outcome. Each 10% drop in RVEF was associated with a 1.3-fold increased risk of the primary outcome (P<0.001) and 1.5-fold increased risk of the secondary outcome (P<0.001). RVEF was an independent predictor following comprehensive covariate adjustment, inclusive of LV ejection fraction. Patients with an RVEF<40% experienced a 3.1-fold risk of the primary outcome (P<0.001) with a 1-year cumulative event rate of 22% versus 7% above this cutoff. CONCLUSIONS: RVEF is a powerful and independent predictor of major adverse cardiac events with broad generalizability across patients with known or suspected cardiovascular disease. These findings support migration towards biventricular phenotyping for the classification of risk in clinical practice. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04367220.

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging-Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy-Naïve Cancer.

Background The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance-based evaluation of cardiac health in patients with chemotherapy-naïve cancer with comparison with a healthy volunteer population. Methods and Results Three-hundred and eighty-one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three-dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak-systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex-matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters. Conclusions The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

Sex-specific relationships between patterns of ventricular remodelling and clinical outcomes.

AIMS: Left ventricular hypertrophy (LVH) is the most common form of myocardial remodelling and predicts adverse outcomes in patients with coronary artery disease (CAD). However, sex-specific prevalence and prognostic significance of LVH patterns are poorly understood. We investigated the sex-specific influence of LVH pattern on clinical outcomes in patients undergoing cardiovascular magnetic resonance (CMR) and coronary angiography following adjustment for co-morbidities including CAD burden. METHODS AND RESULTS: Patients undergoing CMR and coronary angiography between 2005 and 2013 were included. Volumetric measurements of left ventricular (LV) mass with classification of concentric vs. eccentric remodelling patterns were determined from CMR cine images. Multivariable Cox analysis was performed to assess independent associations with the primary outcome of all-cause mortality. In total, 3754 patients were studied (mean age 59.3 ± 13.1 years), including 1039 (27.7%) women. Women were more likely to have concentric remodelling (8.1% vs. 2.1%, P < 0.001), less likely to have eccentric hypertrophy (15.1% vs. 26.8%, P < 0.001) and had a similar prevalence of concentric hypertrophy (6.1 vs. 5.2%, P = 0.296) compared to men. At a median follow-up of 3.7 years, 315 (8.4%) patients died. Following adjustment including CAD burden, concentric hypertrophy was associated with increased all-cause mortality in women [adjusted hazard ratio (HR) 3.48, P < 0.001] and men (adjusted HR 2.57, P < 0.001). Eccentric hypertrophy was associated with all-cause mortality only in women (adjusted HR 1.78, P = 0.047). CONCLUSION: Patterns of LV remodelling differ by sex and LVH and provides prognostic information in both men and women. Our findings support the presence of sex-specific factors influencing LV remodelling.