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Background: Due to the heterogeneity of anatomic anomalies in Ebstein's anomaly (EA), particularly in the subset of patients with atrial septal defect (ASD), hemodynamic changes, which ultimately cause left ventricular (LV) deterioration remain unclear. The current study aimed to investigate the effect of concomitant ASD on LV function using cardiovascular magnetic resonance (CMR) imaging in patients with EA. Methods: This study included 31 EA patients with ASD, 76 EA patients without ASD, 35 patients with simple ASD and 40 healthy controls. Left/right ventricular (RV, the RV was defined as a summation of the functional RV and atrialized RV in EA patients) volumes and functional parameters, LV strain parameters, and echocardiogram indices were compared among the four groups. Associations between variables were evaluated via Spearman or Pearson correlation analyses. The association between risk factors and LV ejection fraction (EF) was determined via multivariate linear regression analysis. Results: Both EA patients and ASD patients had a higher RV/LV end-diastolic volume (RVEDV/LVEDV) as well as lower LV and RV ejection fractions (LVEF/RVEF) compared to healthy controls (all p < 0.05). Moreover, the EA patients with ASD had a significantly higher RVEDV/LVEDV and a lower LVEF and RVEF than those without ASD (all p < 0.05). Multivariate linear regression analysis revealed that the presence of ASD was independently associated with LVEF (β = − 0.337, p < 0.001). The RVEDV/LVEDV index was associated with LVEF (r = − 0.361, p < 0.001). Furthermore, the LV longitudinal peak diastolic strain rate (PDSR) was lower in EA patients with ASD than those without ASD, patients with simple ASD, and healthy controls (p < 0.05). Conclusion: Concomitant ASD is an important risk factor of LV dysfunction in patients with EA, and diastolic dysfunction is likely the predominate mechanism related to LV dysfunction. [ABSTRACT FROM AUTHOR]

Background: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients. Methods: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI = ((LAVmax-LAVmin)/LAVmin) × 100. Results: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort. Conclusions: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation. [ABSTRACT FROM AUTHOR]

Background: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. Methods: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. Results: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13–56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89–54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). Conclusion: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the early morphology and function of the left heart in hypertrophic obstructive cardiomyopathy (HOCM) after transapical beating-heart septal myectomy (TA-BSM) using cardiovascular magnetic resonance (CMR). Materials and methods: Between April 2022 and January 2023, HOCM patients who underwent CMR before and 3 months after TA-BSM were prospectively and consecutively enrolled in the study. Preoperative and postoperative cardiac morphological and functional parameters, including those for the left atrium (LA) and left ventricle (LV), were compared. The left ventricular remodeling index (LVRI) was defined as the ratio between left ventricular mass (LVM) and left ventricular end-diastolic volume (LVEDV). Healthy participants with a similar age and sex distribution were enrolled for comparison. Pearson or Spearman correlation analysis was used to investigate the relationships between the parameters and LVRI. Last, univariate and multivariate linear regression identified variables associated with the LVM index (LVMI) and LVRI. Results: Forty-one patients (mean age ± standard deviation, 46 ± 2 years; 27 males) and 41 healthy control participants were evaluated. Eighteen (44%) HOCM patients were classified as having a sigmoid septum, and 23 patients had a reverse septal curvature. LA volume, diameter and function were significantly improved postoperatively, but still worse than healthy controls (all p < 0.001). Compared to before the operation, left ventricular wall thickness, left ventricular ejection fraction (LVEF), LVMI, and LVRI decreased after TA-BSM (all p < 0.001). The left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-diastolic diameter (LVEDD) decreased in patients with a sigmoid septum. However, LVEDVI and LVEDD increased in those with a reverse septal curvature (both p < 0.001). In addition, both preoperative and postoperative LVRI was positively correlated with LVMI (r = 0.734 and 0.853, both p < 0.001) and maximum wall thickness (r = 0.679 and 0.676, both p < 0.001), respectively. In the multivariable analysis, the weight of the resected myocardium (adjusted β = 0.476, p = 0.005) and △mitral regurgitation degree (adjusted β = − 0.245, p = 0.040) were associated with △LVRI. Last, the △LVOTG (adjusted β = 0.436, p = 0.018) and baseline LVMI (adjusted β = 0.323, p = 0.040) were independently associated with greater left ventricular mass regression after TA-BSM. Conclusion: CMR confirmed early reverse remodeling of left heart morphology and function in HOCM patients following TA-BSM. [ABSTRACT FROM AUTHOR]

Background: Ventricular dyssynchrony and its relationship to clinical outcomes is not well characterized in patients following Fontan palliation. Methods: Single-center retrospective analysis of cardiac magnetic resonance (CMR) imaging of patients with a Fontan circulation and an age-matched healthy comparison cohort as controls. Feature tracking was performed on all slices of a ventricular short-axis cine stack. Circumferential and radial strain, strain rate, and displacement were measured; and multiple dyssynchrony metrics were calculated based on timing of these measurements (including standard deviation of time-to-peak, maximum opposing wall delay, and maximum base-to-apex delay). Primary endpoint was a composite measure including time to death, heart transplant or heart transplant listing (D/HTx). Results: A total of 503 cases (15 y; IQR 10, 21) and 42 controls (16 y; IQR 11, 20) were analyzed. Compared to controls, Fontan patients had increased dyssynchrony metrics, longer QRS duration, larger ventricular volumes, and worse systolic function. Dyssynchrony metrics were higher in patients with right ventricular (RV) or mixed morphology compared to those with LV morphology. At median follow-up of 4.3 years, 11% had D/HTx. Multiple risk factors for D/HTx were identified, including RV morphology, ventricular dilation, dysfunction, QRS prolongation, and dyssynchrony. Ventricular dilation and RV morphology were independently associated with D/HTx. Conclusions: Compared to control LVs, single right and mixed morphology ventricles in the Fontan circulation exhibit a higher degree of mechanical dyssynchrony as evaluated by CMR-FT. Dyssynchrony indices correlate with ventricular size and function and are associated with death or need for heart transplantation. These data add to the growing understanding regarding factors that can be used to risk-stratify patients with the Fontan circulation. [ABSTRACT FROM AUTHOR]

Background: T1, T2 and T1ρ are well-recognized parameters for quantitative cardiac MRI. Simultaneous estimation of these parameters allows for comprehensive myocardial tissue characterization, such as myocardial fibrosis and edema. However, conventional techniques either quantify the parameters individually with separate breath-hold acquisitions, which may result in unregistered parameter maps, or estimate multiple parameters in a prolonged breath-hold acquisition, which may be intolerable to patients. We propose a free-breathing multi-parametric mapping (FB-MultiMap) technique that provides co-registered myocardial T1, T2 and T1ρ maps in a single efficient acquisition. Methods: The proposed FB-MultiMap performs electrocardiogram-triggered single-shot Cartesian acquisition over 16 consecutive cardiac cycles, where inversion, T2 and T1ρ preparations are introduced for varying contrasts. A diaphragmatic navigator was used for prospective through-plane motion correction and the in-plane motion was corrected retrospectively with a group-wise image registration method. Quantitative mapping was conducted through dictionary matching of the motion corrected images, where the subject-specific dictionary was created using Bloch simulations for a range of T1, T2 and T1ρ values, as well as B1 factors to account for B1 inhomogeneities. The FB-MultiMap was optimized and validated in numerical simulations, phantom experiments, and in vivo imaging of 15 healthy subjects and six patients with suspected cardiac diseases. Results: The phantom T1, T2 and T1ρ values estimated with FB-MultiMap agreed well with reference measurements with no dependency on heart rate. In healthy subjects, FB-MultiMap T1 was higher than MOLLI T1 mapping (1218 ± 50 ms vs. 1166 ± 38 ms, p < 0.001). The myocardial T2 and T1ρ estimated with FB-MultiMap were lower compared to the mapping with T2- or T1ρ-prepared 2D balanced steady-state free precession (T2: 41.2 ± 2.8 ms vs. 42.5 ± 3.1 ms, p = 0.06; T1ρ: 45.3 ± 4.4 ms vs. 50.2 ± 4.0, p < 0.001). The pathological changes in myocardial parameters measured with FB-MultiMap were consistent with conventional techniques in all patients. Conclusion: The proposed free-breathing multi-parametric mapping technique provides co-registered myocardial T1, T2 and T1ρ maps in 16 heartbeats, achieving similar mapping quality to conventional breath-hold mapping methods. [ABSTRACT FROM AUTHOR]

Background: Calcimimetic therapy with etelcalcetide (ETEL) has been shown to attenuate the advancement of left ventricular (LV) hypertrophy in hemodialysis patients measured by cardiac magnetic resonance (CMR). The aim of the study was to evaluate whether this effect is accompanied by alterations in LV function and myocardial composition. Methods: This was a post-hoc analysis of a randomized-controlled trial of ETEL versus Alfacalcidol (ALFA) in 62 hemodialysis patients. LV function was assessed using LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) on feature-tracking (FT) CMR. Myocardial tissue characteristics were analyzed using parametric T1 and T2 mapping. Results: Of the total study cohort (n = 62), 48 subjects completed both CMR scans with sufficient quality for FT analysis. In the one-year follow-up, LV GLS deteriorated in the ALFA group, whereas the ETEL group remained stable (LV GLS change: + 2.6 ± 4.6 versus + 0.3 ± 3.8; p = 0.045 when adjusting for randomization factors and baseline LV GLS). We did not observe a difference in the change of LVEF between the two groups (p = 0.513). The impact of ETEL treatment on LV GLS over time remained significant after additional adjustment for the change in LV mass during the study period. ETEL treatment did not significantly affect other CMR parameters. There were no changes in myocardial composition between treatment groups (T1 time change: + 15 ± 42 versus + 10 ± 50; p = 0.411; T2 time change: − 0.13 ± 2.45 versus − 0.70 ± 2.43; p = 0.652). Conclusions: In patients undergoing hemodialysis, treatment with ETEL was protective against deterioration of LV longitudinal function, as evaluated through FT CMR, when compared to the control therapy of ALFA. This effect was not mediated by the change in LV mass. Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT03182699. Unique identifier: NCT03182699. [ABSTRACT FROM AUTHOR]

Background: Longer pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions. Methods: All subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors. Results: Among 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 (95% CI 2.02, 6.73). The HF hazard ratio was 1.26 (95% CI 1.18, 1.33) for each 1 unit increase in PTT which was higher among those preserved (1.70, 95% CI 1.20, 2.41) compared to those with reduced left ventricular ejection fraction (< 50%) (1.18, 95% CI 1.09, 1.27). PTT remained a significant risk factor of hospitalized HF after additional adjustment for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) or left ventricular global longitudinal strain with additionally demonstrated incremental model improvement through likelihood ratio testing. Conclusions: Our findings support the role of PTT in assessing HF risk among patients with broad spectrum of cardiac conditions with reduced as well as preserved ejection fraction. Longer PTT duration is an incremental risk factor for HF when baseline global longitudinal strain and NT-proBNP are taken into consideration. [ABSTRACT FROM AUTHOR]

Online application for survival analysis (OASIS) and its update, OASIS 2, have been widely used for survival analysis in biological and medical sciences. Here, we provide a portable version of OASIS, an all-in-one offline suite, to facilitate secure survival analysis without uploading the data to online servers. OASIS portable provides a virtualized and isolated instance of the OASIS 2 webserver, operating on the users' personal computers, and enables user-friendly survival analysis without internet connection and security issues. [ABSTRACT FROM AUTHOR]

Background: Ischemia of the hypertrophied myocardium due to microvascular dysfunction is related to a worse prognosis in hypertrophic cardiomyopathy (HCM). Stress and rest T1 mapping without contrast agents can be used to assess myocardial blood flow. Herein, we evaluated the potential of non-contrast stress T1 mapping in assessing myocardial injury in patients with HCM. Methods: Forty-five consecutive subjects (31 HCM patients and 14 control subjects) underwent cardiac magnetic resonance (CMR) at 3T, including cine imaging, T1 mapping at rest and during adenosine triphosphate (ATP) stress, late gadolinium enhancement (LGE), and phase-contrast (PC) cine imaging of coronary sinus flow at rest and during stress to assess coronary flow reserve (CFR). PC cine imaging was performed on 25 subjects (17 patients with HCM and 8 control subjects). Native T1 values at rest and during stress were measured using the 16-segment model, and T1 reactivity was defined as the change in T1 values from rest to stress. Results: ATP stress induced a significant increase in native T1 values in both the HCM and control groups (HCM: p < 0.001, control: p = 0.002). T1 reactivity in the HCM group was significantly lower than that in the control group (4.2 ± 0.3% vs. 5.6 ± 0.5%, p = 0.044). On univariate analysis, T1 reactivity correlated with native T1 values at rest, left ventricular mass index, and CFR. Multiple linear regression analysis demonstrated that only CFR was independently correlated with T1 reactivity (β = 0.449; 95% confidence interval, 0.048–0.932; p = 0.032). Furthermore, segmental analysis showed decreased T1 reactivity in the hypertrophied myocardium and the non-hypertrophied myocardium with LGE in the HCM group. Conclusions: T1 reactivity was lower in the hypertrophied myocardium and LGE-positive myocardium compared to non-injured myocardium. Non-contrast stress T1 mapping is a promising CMR method for assessing myocardial injury in patients with HCM. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronization therapy (CRT), but current selection criteria are imprecise, and many patients have limited treatment response. Hemodynamic forces (HDF) have been suggested as a marker for CRT response. The aim of this study was therefore to investigate left ventricular (LV) HDF as a predictive marker for LV remodeling after CRT. Methods: Patients with heart failure, EF < 35% and LBBB (n = 22) underwent CMR with 4D flow prior to CRT. LV HDF were computed in three directions using the Navier–Stokes equations, reported in median N [interquartile range], and the ratio of transverse/longitudinal HDF was calculated for systole and diastole. Transthoracic echocardiography was performed before and 6 months after CRT. Patients with end-systolic volume reduction ≥ 15% were defined as responders. Results: Non-responders had smaller HDF than responders in the inferior-anterior direction in systole (0.06 [0.03] vs. 0.07 [0.03], p = 0.04), and in the apex-base direction in diastole (0.09 [0.02] vs. 0.1 [0.05], p = 0.047). Non-responders had larger diastolic HDF ratio compared to responders (0.89 vs. 0.67, p = 0.004). ROC analysis of diastolic HDF ratio for identifying CRT non-responders had AUC of 0.88 (p = 0.005) with sensitivity 57% and specificity 100% for ratio > 0.87. Intragroup comparison found higher HDF ratio in systole compared to diastole for responders (p = 0.003), but not for non-responders (p = 0.8). Conclusion: Hemodynamic force ratio is a potential marker for identifying patients with heart failure and LBBB who are unlikely to benefit from CRT. Larger-scale studies are required before implementation of HDF analysis into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. Methods: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. Results: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> − 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04–1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12–1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02–1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. Conclusion: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Cardiac magnetic resonance (CMR) parametric mapping sequences offer insights into disease pathophysiology. We propose a novel approach by leveraging T2 mapping in conjunction with T1 and extracellular volume (ECV) mapping to perform a virtual myocardial biopsy. While previous work has attempted to describe myocardial changes in DMD, our inclusion of T2 mapping enables comprehensive categorization of myocardial tissue characteristics of fibrosis, edema, and fat to better understand the pathological composition of the myocardium with disease progression. Methods: DMD patients (n = 49; median: 12 years-old) underwent CMR, including T1, T2, and ECV. Categories were defined as normal, isolated high T1 (normal ECV, high T1, normal T2), fibrosis (high ECV, normal or high T1, normal T2), edema (normal or high ECV, normal or high T1, high T2), fat (normal ECV, low T1, high T2) or fibrofatty (high ECV, low T1, high T2). Results: Median left ventricular ejection fraction (LVEF) was 59% with 27% having LVEF < 55%. Those with normal LVEF and no late gadolinium enhancement (37%) were younger in age (10.5 ± 2.6 vs. 15.0 ± 4.3 years-old, p < 0.001). Native T1 was elevated in at least one slice in 82% of patients. Those with high T2 at any slice (27%) were older (p = 0.005) and had lower LVEF (p = 0.005) compared with subjects with normal T2 (73%). The most common myocardial characterization was fibrosis (43%) followed by isolated high T1 (24%). Of the 13 with high T2, ten were categorized as edema, two as fibrofatty, and one as fat. Conclusion: CMR parametric mapping sequences offer insights into Duchenne cardiomyopathy pathophysiology, which should drive development of therapeutic interventions aimed at these targets. Myocardial fibrosis is common in DMD. Patients with elevated T2 were older and had lower LVEF. Though fat infiltration was present, the majority of subjects with elevated T2 met criteria for myocardial edema. [ABSTRACT FROM AUTHOR]

Background: MRI T2 mapping has been proven to be sensitive to the level of blood oxygenation. We hypothesized that impaired exercise capacity in chronic heart failure is associated with a greater difference between right (RV) to left ventricular (LV) blood pool T2 relaxation times due to a higher level of peripheral blood desaturation, compared to patients with preserved exercise capacity and to healthy controls. Methods: Patients with chronic heart failure (n = 70) who had undergone both cardiac MRI (CMR) and a 6-min walk test (6MWT) were retrospectively identified. Propensity score matched healthy individuals (n = 35) served as control group. CMR analyses included cine acquisitions and T2 mapping to obtain blood pool T2 relaxation times of the RV and LV. Following common practice, age- and gender-adjusted nominal distances and respective percentiles were calculated for the 6MWT. The relationship between the RV/LV T2 blood pool ratio and the results from 6MWT were evaluated by Spearman's correlation coefficients and regression analyses. Inter-group differences were assessed by independent t-tests and univariate analysis of variance. Results: The RV/LV T2 ratio moderately correlated with the percentiles of nominal distances in the 6MWT (r = 0.66) while ejection fraction, end-diastolic and end-systolic volumes showed no correlation (r = 0.09, 0.07 and − 0.01, respectively). In addition, there were significant differences in the RV/LV T2 ratio between patients with and without significant post-exercise dyspnea (p = 0.001). Regression analyses showed that RV/LV T2 ratio was an independent predictor of the distance walked and the presence of post-exercise dyspnea (p < 0.001). Conclusion: The proposed RV/LV T2 ratio, obtained by two simple measurements on a routinely acquired four-chamber T2 map, was superior to established parameters of cardiac function to predict exercise capacity and the presence of post-exercise dyspnea in patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

Objectives: The identification of patients with mitral valve prolapse (MVP) presenting high arrhythmic risk remains challenging. Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) may improve risk stratification. We analyzed the role of CMR-FT parameters in relation to the incidence of complex ventricular arrhythmias (cVA) in patients with MVP and mitral annular disjunction (MAD). Methods: 42 patients with MVP and MAD who underwent 1.5 T CMR were classified as MAD-cVA (n = 23, 55%) in case of cVA diagnosed on a 24-h Holter monitoring and as MAD-noVA in the absence of cVA (n = 19, 45%). MAD length, late gadolinium enhancement (LGE), basal segments myocardial extracellular volume (ECV) and CMR-FT were assessed. Results: LGE was more frequent in the MAD-cVA group in comparison with the MAD-noVA group (78% vs 42%, p = 0.002) while no difference was observed in terms of basal ECV. Global longitudinal strain (GLS) was reduced in MAD-cVA compared to MAD-noVA (− 18.2% ± 4.6% vs − 25.1% ± 3.1%, p = 0.004) as well as global circumferential strain (GCS) at the mid-ventricular level (− 17.5% ± 4.7% vs − 21.6% ± 3.1%, p = 0.041). Univariate analysis identified as predictors of the incidence of cVA: GCS, circumferential strain (CS) in the basal and mid infero-lateral wall, GLS, regional longitudinal strain (LS) in the basal and mid-ventricular inferolateral wall. Reduced GLS [Odd ratio (OR):1.56 (confidence interval (CI) 95%: 1.45–2.47; p < 0.001)] and regional LS in the basal inferolateral wall [OR: 1.62 (CI 95%: 1.22–2.13; p < 0.001)] remained independent prognostic factors in multivariate analysis. Conclusion: In patients with MVP and MAD, CMR-FT parameters are correlated with the incidence of cVA and may be of interest in arrhythmic risk stratification. [ABSTRACT FROM AUTHOR]

Background: Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort. Methods: In total, 1046 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular (LV) end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or heart failure within 12 months after the index event were defined as primary clinical endpoint. Results: LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off at 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4–14.9, p < 0.001) and after adjusting for baseline confounders and LV ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0–9, p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients with impaired LV systolic function (LVEF ≤ 35%; p < 0.001 on log-rank testing). Conclusion: Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond LVEF especially in high-risk patients following AMI. Trial registration ClinicalTrials.gov, NCT00712101 and NCT01612312 [ABSTRACT FROM AUTHOR]

Background: The circle of Willis (CoW) plays a significant role in intracranial atherosclerosis (ICAS). This study investigated the relationship between different types of CoW, atherosclerosis plaque features, and acute ischemic stroke (AIS). Methods: We investigated 97 participants with AIS or transient ischemic attacks (TIA) underwent pre- and post-contrast 3T vessel wall cardiovascular magnetic resonance within 7 days of the onset of symptoms. The culprit plaque characteristics (including enhancement grade, enhancement ratio, high signal in T1, irregularity of plaque surface, and normalized wall index), and vessel remodeling (including arterial remodeling ratio and positive remodeling) for lesions were evaluated. The anatomic structures of the anterior and the posterior sections of the CoW (A-CoW and P-CoW) were also evaluated. The plaque features were compared among them. The plaque features were also compared between AIS and TIA patients. Finally, univariate and multivariate regression analysis was performed to evaluate the independent risk factors for AIS. Result: Patients with incomplete A-CoW showed a higher plaque enhancement ratio (P = 0.002), enhancement grade (P = 0.01), and normalized wall index (NWI) (P = 0.018) compared with the patients with complete A-CoW. A higher proportion of patients with incomplete symptomatic P-CoW demonstrated more culprit plaques with high T1 signals (HT1S) compared with those with complete P-CoW (P = 0.013). Incomplete A-CoW was associated with a higher enhancement grade of the culprit plaques [odds ratio (OR):3.84; 95% CI: 1.36–10.88, P = 0.011], after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Incomplete symptomatic P-CoW was associated with a higher probability of HT1S (OR:3.88; 95% CI: 1.12–13.47, P = 0.033), after adjusting for clinical risk factors such as age, sex, smoking, hypertension, hyperlipemia, and diabetes mellitus. Furthermore, an irregularity of the plaque surface (OR: 6.24; 95% CI: 2.25–17.37, P < 0.001), and incomplete symptomatic P-CoW (OR: 8.03, 95% CI: 2.43–26.55, P = 0.001) were independently associated with AIS. Conclusions: This study demonstrated that incomplete A-CoW was associated with enhancement grade of the culprit plaque, and incomplete symptomatic side P-CoW was associated with the presence of HT1S of culprit plaque. Furthermore, an irregularity of plaque surface and incomplete symptomatic side P-CoW were associated with AIS. [ABSTRACT FROM AUTHOR]

Background: Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality. Methods: Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations. Results: One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 [0.24–0.80], p = 0.007) and total arrhythmia (OR 0.56 [0.37–0.92], p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality. Conclusions: Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathy (CMP) is the most common cause of mortality in Duchenne muscular dystrophy (DMD), though the age of onset and clinical progression vary. We applied a novel 4D (3D + time) strain analysis method using cine cardiovascular magnetic resonance (CMR) imaging data to determine if localized strain metrics derived from 4D image analysis would be sensitive and specific for characterizing DMD CMP. Methods: We analyzed short-axis cine CMR image stacks from 43 DMD patients (median age: 12.23 yrs [10.6–16.5]; [interquartile range]) and 25 male healthy controls (median age: 16.2 yrs [13.3–20.7]). A subset of 25 male DMD patients age-matched to the controls (median age: 15.7 yrs [14.0-17.8]) was used for comparative metrics. CMR images were compiled into 4D sequences for feature-tracking strain analysis using custom-built software. Unpaired t-test and receiver operator characteristic area under the curve (AUC) analysis were used to determine statistical significance. Spearman's rho was used to determine correlation. Results: DMD patients had a range of CMP severity: 15 (35% of total) had left ventricular ejection fraction (LVEF) > 55% with no findings of myocardial late gadolinium enhancement (LGE), 15 (35%) had findings of LGE with LVEF > 55% and 13 (30%) had LGE with LVEF < 55%. The magnitude of the peak basal circumferential strain, basal radial strain, and basal surface area strain were all significantly decreased in DMD patients relative to healthy controls (p < 0.001) with AUC values of 0.80, 0.89, and 0.84 respectively for peak strain and 0.96, 0.91, and 0.98 respectively for systolic strain rate. Peak basal radial strain, basal radial systolic strain rate, and basal circumferential systolic strain rate magnitude values were also significantly decreased in mild CMP (No LGE, LVEF > 55%) compared to a healthy control group (p < 0.001 for all). Surface area strain significantly correlated with LVEF and extracellular volume (ECV) respectively in the basal (rho = − 0.45, 0.40), mid (rho = − 0.46, 0.46), and apical (rho = − 0.42, 0.47) regions. Conclusion: Strain analysis of 3D cine CMR images in DMD CMP patients generates localized kinematic parameters that strongly differentiate disease from control and correlate with LVEF and ECV. [ABSTRACT FROM AUTHOR]

Background: Assessing the structure and function of left atrium (LA) is crucial in hypertrophic obstructive cardiomyopathy (HOCM) because LA remodeling correlates with atrial fibrillation. However, few studies have investigated the potential effect of myomectomy on LA phasic remodeling in HOCM after myectomy using cardiovascular magnetic resonance (CMR) feature tracking (FT). This study aims to evaluate the LA structural and functional remodeling with HOCM after myectomy by CMR-FT and to further investigate the determinants of LA reverse remodeling. Methods: In this single-center study, we retrospectively studied 88 patients with HOCM who received CMR before and after myectomy between January 2011 and June 2021. Preoperative and postoperative LA parameters derived from CMR-FT were compared, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster function (booster EF, active strain [εa], late peak negative strain rate [SRa]). Eighty-six healthy participants were collected for comparison. Univariate and multivariate linear regression identified variables associated with the rate of change of εa. Results: Compared with preoperative parameters, LA reservoir function (total EF, εs, SRs), booster function (booster EF, εa, SRa), and SRe were significantly improved after myectomy (all P < 0.05), while no significant differences were observed in passive EF and εe. Postoperative patients with HOCM still had larger LA and worse LA function than healthy controls (all P < 0.05). After analyzing the rates of change in LA parameters, LA boost function, especially εa, showed the most dramatic improvement beyond the improvements in reservoir function, conduit function, and volume. In multivariable regression analysis, minimum LA volume index (adjusted β = − 0.39, P < 0.001) and Δleft ventricular outflow tract (LVOT) pressure gradient (adjusted β = − 0.29, P = 0.003) were significantly related to the rate of change of εa. Conclusions: Patients with HOCM after septal myectomy showed LA reverse remodeling with a reduction in LA size and restoration in LA reservoir and booster function but unchanged LA conduit function. Among volumetric and functional changes, booster function had the greatest improvement postoperatively. Besides, preoperative LAVmin index and ΔLVOT might be potential factors associated with the degree of improvement in εa. [ABSTRACT FROM AUTHOR]

Background: Data regarding cardiovascular magnetic resonance (CMR) reference values in athletes have not been well determined yet. Using CMR normal reference values derived from the general population may be misleading in athletes and may have clinical implications. Aims: To determine reference ventricular dimensions and function parameters and ratios by CMR in high performance athletes. Methods: Elite athletes and age‐ and gender‐matched sedentary healthy controls were included. Anatomical and functional variables, including biventricular volumes, mass, systolic function, wall thickness, sphericity index and longitudinal function were determined by CMR. Results: A total of 148 athletes (29.2 ± 9.1 years; 64.8% men) and 124 controls (32.1 ± 10.5 years; 67.7% men) were included. Left ventricular (LV) mass excluding papillary muscles was 67 ± 13 g/m2 in the control group and increased from 65 ± 14 g/m2 in the low intensity sport category to 83 ± 16 g/m2 in the high cardiovascular demand sport category; P < 0.001. Regarding right ventricular (RV) mass, the data were 20 ± 5, 31 ± 6, and 38 ± 8 g/m2, respectively; P < 0.001. LV and RV volumes, and wall thickness were higher in athletes than in the control group, and also increased with sport category. However, LV and RV ejection fractions were similar in both groups. LV and RV dimensions, wall thickness and LV/RV ratios reference parameters for athletes are provided. Conclusions: LV and RV masses, volumes, and wall thicknesses are higher in athletes than in sedentary subjects. Specific CMR reference ranges for athletes are provided and can be used as reference levels, rather than the standard upper limits used for the general population to exclude cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vein (PV) stenosis represents a rare but serious complication following radiofrequency ablation of atrial fibrillation with a comprehensive diagnosis including morphological stenosis grading together with the assessment of its functional consequences being imperative within the relatively narrow window for therapeutic intervention. The present study determined the clinical utility of a combined, single-session cardiovascular magnetic resonance (CMR) imaging protocol integrating pulmonary perfusion and PV angiographic assessment for pre-procedural planning and follow-up of patients referred for interventional PV stenosis treatment. Methods: CMR examinations (cine imaging, dynamic pulmonary perfusion, three-dimensional PV angiography) were performed in 32 consecutive patients prior to interventional treatment of PV stenosis and at 1-day and 3-months follow-up. Degree of PV stenosis was visually determined on CMR angiography; visual and quantitative analysis of pulmonary perfusion imaging was done for all five lung lobes. Results: Interventional treatment of PV stenosis achieved an acute procedural success rate of 90%. Agreement between visually evaluated pulmonary perfusion imaging and the presence or absence of a ≥ 70% PV stenosis was nearly perfect (Cohen's kappa, 0.96). ROC analysis demonstrated high discriminatory power of quantitative pulmonary perfusion measurements for the detection of ≥ 70% PV stenosis (AUC for time-to-peak enhancement, 0.96; wash-in rate, 0.93; maximum enhancement, 0.90). Quantitative pulmonary perfusion analysis proved a very large treatment effect attributable to successful PV revascularization already after 1 day. Conclusion: Integration of CMR pulmonary perfusion imaging into the clinical work-up of patients with PV stenosis allowed for efficient peri-procedural stratification and follow-up evaluation of revascularization success. [ABSTRACT FROM AUTHOR]

Background High energy intake from non–nutrient-dense sources correlates with poorer diet quality. Objectives The aims were to 1) estimate total energy intake and energy from solid fats and added sugars combined (SoFAS) and identify their top food category sources for ages 2–18 y in 2015–2018 and 2) describe trends over time in 2009–2018. Methods Data were from the NHANES. Pairwise differences were examined using univariate t statistics (2015–2018, n  = 5038), and trends by age and over time (2009–2018, n  = 14,038) were examined using orthogonal polynomials. Results In 2015–2018, SoFAS contributed a mean (SE) of 30.0% (0.3%) of total energy. Solid fats [16.1% (0.2%)] and added sugars [13.8% (0.2%)] each contributed >10%. The contribution of added sugars increased with age from 11.1% (2–3 y) to 14.4% (14–18 y), and was higher for all other race/Hispanic origins than non-Hispanic Asians. The top 5 sources of energy were sweet bakery products, savory snacks, pizza, other mixed dishes, and unflavored milk, and for SoFAS also included soft drinks, other desserts, candy, and snack bars. Total energy did not change between 2009 and 2018, but energy from SoFAS, and servings of solid fats, and added sugars declined. The contribution of unflavored milk to total energy declined for all ages and most race/Hispanic origins. Fruit drinks (all ages) and soft drinks (9–18 y) remained among top added sugars sources despite declines. The contribution of sweet bakery products to energy from SoFAS increased for most ages and candy and snack bars to energy from added sugars. Conclusions In 2015–2018, SoFAS contributed >30% of total energy for ages 2–18 y, which doubled the Dietary Guidelines for Americans' recommended limit of 15%. The top 5 sources of total energy were similar to those of solid fats, and those of SoFAS similar to those of added sugars. These results may inform public health efforts for improving diet quality. [ABSTRACT FROM AUTHOR]

Background: Cardiac diffusion tensor imaging (cDTI) using cardiovascular magnetic resonance (CMR) is a novel technique for the non-invasive assessment of myocardial microstructure. Previous studies have shown myocardial infarction to result in loss of sheetlet angularity, derived by reduced secondary eigenvector (E2A) and reduction in subendocardial cardiomyocytes, evidenced by loss of myocytes with right-handed orientation (RHM) on helix angle (HA) maps. Myocardial strain assessed using feature tracking-CMR (FT-CMR) is a sensitive marker of sub-clinical myocardial dysfunction. We sought to explore the relationship between these two techniques (strain and cDTI) in patients at 3 months following ST-elevation MI (STEMI). Methods: 32 patients (F = 28, 60 ± 10 years) underwent 3T CMR three months after STEMI (mean interval 105 ± 17 days) with second order motion compensated (M2), free-breathing spin echo cDTI, cine gradient echo and late gadolinium enhancement (LGE) imaging. HA maps divided into left-handed HA (LHM, − 90 < HA < − 30), circumferential HA (CM, − 30° < HA < 30°), and right-handed HA (RHM, 30° < HA < 90°) were reported as relative proportions. Global and segmental analysis was undertaken. Results: Mean left ventricular ejection fraction (LVEF) was 44 ± 10% with a mean infarct size of 18 ± 12 g and a mean infarct segment LGE enhancement of 66 ± 21%. Mean global radial strain was 19 ± 6, mean global circumferential strain was − 13 ± − 3 and mean global longitudinal strain was − 10 ± − 3. Global and segmental radial strain correlated significantly with E2A in infarcted segments (p = 0.002, p = 0.011). Both global and segmental longitudinal strain correlated with RHM of infarcted segments on HA maps (p < 0.001, p = 0.003). Mean Diffusivity (MD) correlated significantly with the global infarct size (p < 0.008). When patients were categorised according to LVEF (reduced, mid-range and preserved), all cDTI parameters differed significantly between the three groups. Conclusion: Change in sheetlet orientation assessed using E2A from cDTI correlates with impaired radial strain. Segments with fewer subendocardial cardiomyocytes, evidenced by a lower proportion of myocytes with right-handed orientation on HA maps, show impaired longitudinal strain. Infarct segment enhancement correlates significantly with E2A and RHM. Our data has demonstrated a link between myocardial microstructure and contractility following myocardial infarction, suggesting a potential role for CMR cDTI to clinically relevant functional impact. [ABSTRACT FROM AUTHOR]

Background There has been growing interest in studying postprandial glucose responses using continuous glucose monitoring (CGM) in nondiabetic individuals. Accurate measurement of glucose responses to meals can facilitate applications such as precision nutrition and early detection of diabetes. Objectives We aimed to quantify the discordance between simultaneous postprandial glucose measurements made using plasma and CGM. Methods We studied 10 nondiabetic older adults who randomly consumed 9 predefined meals of varying macronutrient compositions. Glucose was measured for 8 h after the meal by the CGM, blood samples for plasma collection were taken regularly, and plasma glucose was quantified using gold-standard laboratory measurement and a fingerstick blood glucose meter. The primary outcome measured was the mean absolute relative difference (MARD) of CGM and fingerstick measurements relative to the gold standard. Secondary outcomes were Bland–Altman statistics, Clarke Error Grid, and time in range metrics. Additional subgroup analyses were performed by stratifying the postprandial glucose measurements based on the macronutrient composition of the meals. Results When compared against the gold-standard postprandial glucose measurements, the fingerstick meter was more accurate (MARD: 8.0%; 95% CI: 7.6%, 8.6%) than the CGM (MARD: 13.7%; 95% CI: 13.1%, 14.3%; P  < 0.0001). After the meals, Bland–Altman analysis demonstrated that the CGM underestimated the 8-h gold-standard glucose rise by 12.8 mg/dL on average (P  < 0.0001), whereas the fingerstick meter did so by 5.5 mg/dL on average (P  < 0.0001). The CGM underestimated the time spent in the 70–180 mg/dL range (P  = 0.002) and overestimated the time spent <70 mg/dL (P  < 0.0001) compared with the other 2 methods. Conclusions We discovered discordance between gold standard, fingerstick, and CGM in measuring plasma glucose concentrations after a meal. Consequently, emerging applications of CGM in healthy individuals, such as precision nutrition and diabetes onset prediction, may need to account for these discordances. This trial was registered at clinicaltrials.gov as NCT04928872. [ABSTRACT FROM AUTHOR]

Background The Mediterranean diet is associated with the prevention of diabetes, cardiovascular disease, and cancer, all of which are linked to intestinal barrier impairment. Objectives Here, we hypothesize that the Mediterranean diet, possibly via the induction of short-chain fatty acids (SCFAs), improves intestinal barrier integrity. Furthermore, we aim to establish novel personalized nutrition advice based on machine learning algorithms. Methods We studied 260 women with intestinal barrier impairment. The women were allocated to follow either a Mediterranean diet or a control diet for 3 mo. Intestinal permeability was assessed by measuring lipopolysaccharide binding protein (LBP) in plasma and zonulin in feces. SCFA concentrations were analyzed in feces. Bi- and multivariate analyses and machine learning algorithms (random forest classification) were conducted. Results Particularly in the intervention group, adherence to the Mediterranean diet increased, whereas plasma LBP and fecal zonulin concentrations decreased (all q  < 0.001 for the intervention group, all q  < 0.1 for control group). In the intervention group, fecal SCFA concentrations increased (propionate + 19%; butyrate + 44%; both q  < 0.001). Multivariate analyses showed that adherence to the Mediterranean diet was associated with SCFA concentrations (all q  < 0.001) and inversely associated with LBP and zonulin concentrations (all q  < 0.02). Mediation analyses identified propionate and butyrate as the key mechanistic link between diet and intestinal permeability integrity. Accordingly, using baseline SCFA data, we could predict the effect of the Mediterranean diet on intestinal permeability using a machine learning algorithm (receiver operating characteristic AUC: 0.78–0.96). Conclusions Our data suggest that SCFAs are key mediators for the relation between diet and gut health. Assessment of SCFAs may form a basis for personalized nutrition in future clinical care. These results need to be verified in larger studies powered for this purpose, comprising different study populations. The trial was registered at clinicaltrials.gov as NCT02087592 and NCT02516540. [ABSTRACT FROM AUTHOR]

This reflection article addresses a difficulty faced by scholars and practitioners working with numbers about people, which is that those who study people want numerical data about these people. Unfortunately, time and time again, this numerical data about people is wrong. Addressing the potential causes of this wrongness, we present examples of analyzing people numbers, i.e., numbers derived from digital data by or about people, and discuss the comforting illusion of data validity. We first lay a foundation by highlighting potential inaccuracies in collecting people data, such as selection bias. Then, we discuss inaccuracies in analyzing people data, such as the flaw of averages, followed by a discussion of errors that are made when trying to make sense of people data through techniques such as posterior labeling. Finally, we discuss a root cause of people data often being wrong - the conceptual conundrum of thinking the numbers are counts when they are actually measures. Practical solutions to address this illusion of data validity are proposed. The implications for theories derived from people data are also highlighted, namely that these people theories are generally wrong as they are often derived from people numbers that are wrong. [ABSTRACT FROM AUTHOR]

Background Short-term randomized trials suggest that a 500 mg/d vitamin C supplement reduces serum urate, whereas observational studies show vitamin E is inversely associated with gout risk. Objectives We evaluated the effect of supplemental vitamin C (prespecified primary exposure) and vitamin E (prespecified secondary exposure) on new diagnoses of gout. Methods We performed a post hoc analysis of data from the Physicians' Health Study II, a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/d) and vitamin E (400 IU every other day). The primary outcome was new gout diagnoses, self-reported at baseline and throughout the follow-up period of ≤10 y. Results Of 14,641 randomly assigned male physicians in our analysis, the mean age was 64 ± 9 y; 1% were Black, and 6.5% had gout prior to randomization. The incidence rate of new gout diagnoses during follow-up was 8.0 per 1000 person-years among those assigned vitamin C compared with 9.1 per 1000 person-years among those assigned placebo. The vitamin C assignment reduced new gout diagnoses by 12% (HR: 0.88; 95% CI: 0.77, 0.99; P  = 0.04). These effects were greatest among those with a BMI <25 kg/m 2 (P -interaction = 0.01). Vitamin E was not associated with new gout diagnoses (HR: 1.05; 95% CI: 0.92, 1.19; P  = 0.48). Conclusions Vitamin C modestly reduced the risk of new gout diagnoses in middle-aged male physicians. Additional research is needed to determine the effects of higher doses of vitamin C supplementation on serum urate and gout flares in adults with established gout. The Physicians' Health Study II is registered at clinicaltrials.gov (identifier: NCT00270647). [ABSTRACT FROM AUTHOR]

Background Slow gastric emptying occurs frequently during critical illness and is roughly quantified at bedside by large gastric residual volumes (GRVs). A previously published trial (The Augmented versus Routine approach to Giving Energy Trial; TARGET) reported larger GRVs with energy-dense (1.5 kcal/mL) compared with standard (1.0 kcal/mL) enteral nutrition (EN), warranting further exploration. Objective To assess the incidence, risk factors, duration, and timing of large GRVs (≥250 mL) and its relation to clinical outcomes in mechanically ventilated adults. Methods A post-hoc analysis of TARGET data in patients with ≥1 GRV recorded. Data are n (%) or median [IQR]. Results Of 3876 included patients, 1777 (46%) had ≥1 GRV ≥250 mL, which was more common in males (50 compared with 39%; P < 0.001) and in patients receiving energy-dense compared with standard EN (52 compared with 40%; RR = 1.27 (95% CI: 1.19, 1.36); P < 0.001) in whom it also lasted longer (1 [0–2] compared with 0 [0–1] d; P < 0.001), with no difference in time of onset after EN initiation (day 1 [0–2] compared with 1 [0–2]; P = 0.970). Patients with GRV ≥250 mL were more likely to have the following: vasopressor administration (88 compared with 76%; RR = 1.15 [1.12, 1.19]; P < 0.001), positive blood cultures (16 compared with 8%; RR = 1.92 [1.60, 2.31]; P < 0.001), intravenous antimicrobials (88 compared with 81%; RR = 1.09 [1.06, 1.12]; P < 0.001), and prolonged intensive care unit (ICU) stay (ICU-free days to day 28; 12.9 [0.0–21.0] compared with 20.0 [3.9–24.0]; P < 0.001), hospital stay (hospital-free days to day 28: 0.0 [0.0–12.0] compared with 7.0 [0.0–17.6] d; P < 0.001), ventilatory support (ventilator-free days to day 28: 16.0 [0.0–23.0] compared with 22.0 [8.0–25.0]; P < 0.001), and a higher 90-d mortality (29 compared with 23%; adjusted: RR = 1.17 [1.05, 1.30]; P = 0.003). Conclusion Large GRVs were more common in males and those receiving energy-dense formulae, occurred early and were short-lived, and were associated with a number of negative clinical sequelae, including increased mortality, even when adjusted for illness severity. This trial was registered at clinicaltrials.gov as NCT02306746. [ABSTRACT FROM AUTHOR]

Background Hybrid methodologies have gained continuing interest as unique data reduction techniques for establishing a direct link between dietary exposures and clinical outcomes. Objectives We aimed to compare partial least squares (PLS) and reduced rank regression (RRR) in identifying a dietary pattern associated with a high cardiovascular disease (CVD) risk in Canadian adults, construct PLS- and RRR-based simplified dietary patterns, and assess associations between the 4 dietary pattern scores and CVD risk. Methods Data were collected from 24-h dietary recalls of adult respondents in the 2 cycles of the nationally representative Canadian Community Health Survey (CCHS)-Nutrition: CCHS 2004 linked to health administrative databases (n = 12,313) and CCHS 2015 (n = 14,020). Using 39 food groups, PLS and RRR were applied for identification of an energy-dense (ED), high-saturated-fat (HSF), and low-fiber-density (LFD) dietary pattern. Associations of the derived dietary pattern scores with lifestyle characteristics and CVD risk were examined using weighted multivariate regression and weighted multivariable-adjusted Cox proportional hazard models, respectively. Results PLS and RRR identified highly similar ED, HSF, and LFD dietary patterns with common high positive loadings for fast food, carbonated drinks, salty snacks, and solid fats, and high negative loadings for fruit, dark green vegetables, red and orange vegetables, other vegetables, whole grains, and legumes and soy (≥|0.17|). Food groups with the highest loadings were summed to form simplified pattern scores. Although the dietary patterns were not significantly associated with CVD risk, they were positively associated with 402-kcal/d higher energy intake (P -trends < 0.05) and higher obesity risk (PLS: OR: 2.09; 95% CI: 1.62, 2.70; RRR: OR: 1.76; 95% CI: 1.44, 2.17) (P -trends < 0.0001) in the fourth quartiles. Conclusions PLS and RRR were shown to be equally effective for the derivation of a high-CVD-risk dietary pattern among Canadian adults. Further research is warranted on the role of major dietary components in cardiovascular health. [ABSTRACT FROM AUTHOR]

Background Consumption of meals bought from out-of-home sources is a suggested risk factor for obesity, but the supporting evidence is mixed. Objectives To investigate the association between consumption of different types of meals and BMI or percent body fat. Methods Data were from the UK Biobank in response to a "Type of Meals Eaten" survey, which specified the sources of the meals consumed over the previous 24 h. Because direction of causality is unknown, the data were analyzed with meal choice as the dependent variable first and then BMI as the dependent variable second. Results The total number of participants was 5197 (2841 women and 2356 men). Participants with higher BMI and percent body fat were more likely to report consuming takeaway and/or delivery meals, with prevalence ORs (95% CIs) of 2.12 (95% CI: 1.40, 3.22; Bonferroni P  < 0.0001) for women's adjusted BMI, 1.95 (95% CI: 1.30, 2.93; Bonferroni P  < 0.0001) for women's adjusted percent body fat, 1.65 (95% CI: 1.05, 2.59; Bonferroni P  < 0.002) for men's adjusted BMI, and 1.41 (95% CI: 0.70, 2.84; Bonferroni P  < 0.01) for men's adjusted percent body fat. As BMI and percent body fat increased, both men and women were increasingly less likely to report having consumed a home-cooked and prepared meal during the previous 24 h. Analyzing the data with BMI and percent body fat as the dependent variable showed that both unadjusted and adjusted BMI and percent body fat were higher in individuals reporting consumption of takeaway and delivery foods the previous day and lower in those consuming homecooked meals. The probability of having consumed a meal that was prepared and eaten at a restaurant and/or café was also associated with BMI and percent fat among men but not women. Conclusions Homecooked meals were more often consumed by those with low BMI and percent body fat, whereas delivery and takeaway meals were more often eaten by individuals with higher BMI. Consumption of fast-food/café meals was not consistently associated with BMI or percent body fat. The direction of causality in these associations cannot be inferred from this cross-sectional study. [ABSTRACT FROM AUTHOR]

Backgrounds: Synthetic late gadolinium enhancement (LGE) images are less sensitive to inversion time (TI) and robust to motion artifact, because it is generated retrospectively by post-contrast T1-mapping images. To explore the clinical applicability of synthetic LGE, we investigated the image quality and diagnostic accuracy of synthetic LGE images, in comparison to that of conventional LGE for various disease groups. Method and materials: From July to November 2019, a total of 98 patients who underwent cardiovascular magnetic resonance imaging (CMR), including LGE and T1-mapping sequences, with suspicion of myocardial abnormality were retrospectively included. Synthetic magnitude inversion-recovery (IR) and phase-sensitive IR (PSIR) images were generated through calculations based on the post-contrast T1-mapping sequence. Three cardiothoracic radiologists independently analyzed the image quality of conventional and synthetic LGE images on an ordinal scale with per-segment basis and the image qualities were compared with chi-square test. The agreement of LGE detection was analyzed on per-patient and per-segment basis with Cohen's kappa test. In addition, the LGE area and percentage were semi-quantitatively analyzed for LGE positive ischemic (n = 14) and hypertrophic cardiomyopathy (n = 13) subgroups by two cardiothoracic radiologists. The difference of quantified LGE area and percentage between conventional and synthetic LGE images were assessed with Mann–Whitney U-test and the inter-reader agreement was assessed with Bland–Altman analysis. Results: The image quality of synthetic images was significantly better than conventional images in both magnitude IR and PSIR through all three observers (P < 0.001, all). The agreements of per-patient and per-segment LGE detection rates were excellent (kappa = 0.815–0.864). The semi-quantitative analysis showed no significant difference in the LGE area and percentage between conventional and synthetic LGE images. In the inter-reader agreement showed only small systematic differences in both magnitude IR and PSIR and synthetic LGE images showed smaller systematic biases compared to conventional LGE images. Conclusion: Compared to conventional LGE images, synthetic LGE images have better image quality in real-life clinical situation. [ABSTRACT FROM AUTHOR]

Background: Both stenosis rate and intraplaque hemorrhage (IPH) are important predictors of stroke risk. Simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) cardiovascular magnetic resonance (CMR) imaging can detect both stenosis rate and IPH. We aimed to evaluate consistency between SNAP and digital subtraction angiography (DSA) to assess symptomatic patients with stroke and explore the performance of SNAP to identify IPH and the clinical factors associated with IPH. Methods: Eighty-one symptomatic patients with stroke, admitted to Wuhan Union Hospital who underwent CMR high-resolution vessel wall imaging (HR-VWI) and SNAP, were retrospectively identified. For patients who received interventional therapy, the imaging functions of SNAP and HR-VWI were compared with DSA. The diameters of the intracranial and carotid vessels were measured, and stenotic vessels were identified. The consistency of SNAP and HR-VWI in identifying IPH was also examined, and the correlations between IPH and clinical factors were analyzed. Results: SNAP was more consistent with DSA than HR-VWI in measuring vascular stenosis (intraclass correlation coefficient [ICC]SNAP-DSA = 0.917, ICC HR-VWI-DSA = 0.878). Regarding the diameter measurements of each intracranial and carotid vessel segment, SNAP was superior or similar to HR-VWI, and both were consistent with DSA in the measurement of major intracranial vascular segments. HR-VWI and SNAP exhibited acceptable agreement in identifying IPH (Kappa = 0.839, 95% confidence interval [CI]: 0.704–0.974). Patients who underwent interventional therapy had a higher plaque burden (P < 0.001). Patients with IPH had lower levels of high-density lipoprotein cholesterol (HDL) (P = 0.038) and higher levels of blood glucose (P = 0.007) and cystatin C (P = 0.040). Conclusions: CMR SNAP is consistent with DSA in measuring vessel diameters and identifying atherosclerosis stenosis in each intracranial and carotid vessel segment. SNAP is also a potential alternative to HR-VWI in identifying stenosis and IPH. [ABSTRACT FROM AUTHOR]

Background: Both stenosis rate and intraplaque hemorrhage (IPH) are important predictors of stroke risk. Simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) cardiovascular magnetic resonance (CMR) imaging can detect both stenosis rate and IPH. We aimed to evaluate consistency between SNAP and digital subtraction angiography (DSA) to assess symptomatic patients with stroke and explore the performance of SNAP to identify IPH and the clinical factors associated with IPH. Methods: Eighty-one symptomatic patients with stroke, admitted to Wuhan Union Hospital who underwent CMR high-resolution vessel wall imaging (HR-VWI) and SNAP, were retrospectively identified. For patients who received interventional therapy, the imaging functions of SNAP and HR-VWI were compared with DSA. The diameters of the intracranial and carotid vessels were measured, and stenotic vessels were identified. The consistency of SNAP and HR-VWI in identifying IPH was also examined, and the correlations between IPH and clinical factors were analyzed. Results: SNAP was more consistent with DSA than HR-VWI in measuring vascular stenosis (intraclass correlation coefficient [ICC]SNAP-DSA = 0.917, ICC HR-VWI-DSA = 0.878). Regarding the diameter measurements of each intracranial and carotid vessel segment, SNAP was superior or similar to HR-VWI, and both were consistent with DSA in the measurement of major intracranial vascular segments. HR-VWI and SNAP exhibited acceptable agreement in identifying IPH (Kappa = 0.839, 95% confidence interval [CI]: 0.704–0.974). Patients who underwent interventional therapy had a higher plaque burden (P < 0.001). Patients with IPH had lower levels of high-density lipoprotein cholesterol (HDL) (P = 0.038) and higher levels of blood glucose (P = 0.007) and cystatin C (P = 0.040). Conclusions: CMR SNAP is consistent with DSA in measuring vessel diameters and identifying atherosclerosis stenosis in each intracranial and carotid vessel segment. SNAP is also a potential alternative to HR-VWI in identifying stenosis and IPH. [ABSTRACT FROM AUTHOR]

Background The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. Objectives We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. Methods This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n  = 101) or placebo (n  = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. Results The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. Conclusions The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. This trial was registered at clinicaltrials.gov as NCT04449718. [ABSTRACT FROM AUTHOR]

Background There remains a limited understanding of the metabolic perturbations, beyond phenylalanine (Phe) metabolism, that contribute to phenotypic variability in phenylketonuria (PKU). Objectives This study aimed to characterize changes in the PKU plasma metabolome following a 5-d metabolic camp intervention and to compare PKU profiles with those of matched healthy controls. Methods In 28 females (aged 12–57 y), fasting plasma samples were collected on the first (day 1) and final (day 5) days of camp to measure metabolic control and to complete untargeted metabolomic profiling. Three-day dietary records were collected to assess changes in dietary adherence and composition. Univariate (Wilcoxon signed-rank and Mann–Whitney U test) and multivariate (random forest, hierarchical clustering) analyses were performed to identify clinical and metabolic features that were associated with the intervention and disease state. Results Relative to healthy controls, Phe catabolites, ketones, and carnitine- and glycine-conjugated fatty acids were elevated in females with PKU at baseline, whereas fatty acylcholine metabolites were substantially lower. After the camp intervention, plasma Phe concentrations decreased [median change: –173 µmol/L (IQR: –325, –28 µmol/L)] and 70% of PKU participants demonstrated improved dietary adherence by decreasing Phe intake and/or increasing medical food consumption. This was accompanied by a shift in abundance for 223 metabolites (q  < 0.05). Compounds associated with the metabolism of Phe, fatty acids, and choline contributed most to profile differences between camp days 1 and 5. Conclusions In females with PKU, untargeted metabolomics identified prominent perturbations in amino acid and lipid metabolites associated with bioenergetic impairment and oxidative stress. Choline-conjugated lipids could have fundamental roles in these pathways and they have not been previously evaluated in PKU. A short-term camp intervention was effective for improving or fully normalizing the abundance of the identified discriminatory metabolites. [ABSTRACT FROM AUTHOR]

Background Diet quality scores (DQSs) are frequently used to study diet–disease relations but the validity of these scores derived from FFQs has rarely been evaluated. Objectives To evaluate the validity and reproducibility of 6 commonly used DQSs derived from the FFQ, including the Alternate Healthy Eating Index–2010, Dietary Approaches to Stop Hypertension Trial score, alternative Mediterranean diet score, and 3 plant-based diet indices (overall, healthful, and unhealthful). Methods This analysis included 1394 participants from the Men's Lifestyle Validation Study (N = 652) and the Women's Lifestyle Validation Study (N = 742). Participants completed a 152-item FFQ at the beginning of the study and 1 y later, as well as completed 2 weighed 7-d dietary records (7DDRs) and donated 2 blood samples 6 mo apart between FFQ assessments. The reproducibility of the FFQs was evaluated by rank intraclass correlation coefficients (ICCs). The validity was assessed by comparing FFQ-derived DQSs with those from the average of two 7DDRs using Spearman rank correlation coefficients deattenuated for random measurement error in the 7DDRs (r s). Furthermore, we calculated the correlations between DQSs and plasma biomarkers of diet, including fatty acids, folate, carotenoids, retinol, and α- and γ-tocopherol. Results Six FFQ-derived DQSs demonstrated moderate to high reproducibility (energy-adjusted ICCs: 0.61–0.84) and validity (energy-adjusted, deattenuated r s = 0.56–0.80) in both men and women. We consistently observed expected correlations between FFQ-derived DQSs with plasma fatty acids, including long-chain n–3 (ω-3) and trans fatty acids, most carotenoids, and γ-tocopherol (r s > 0.2). Conclusions Our study demonstrates the validity of the FFQ to evaluate overall diet quality using 6 commonly used DQSs. In addition, these DQSs have qualitatively demonstrated biological relevance, as indicated by their correlations with circulating biomarkers. [ABSTRACT FROM AUTHOR]

Background Dietary exposure assessments are a critical issue in evaluating human nutrition studies; however, nutrition-specific criteria are not consistently included in existing bias assessment tools. Objectives Our objective was to develop a set of risk of bias (RoB) tools that integrated nutrition-specific criteria into validated generic assessment tools to address RoB issues, including those specific to dietary exposure assessment. Methods The Nutrition QUality Evaluation Strengthening Tools (NUQUEST) development and validation process included 8 steps. The first steps identified 1) a development strategy; 2) generic assessment tools with demonstrated validity; and 3) nutrition-specific appraisal issues. This was followed by 4) generation of nutrition-specific items and 5) development of guidance to aid users of NUQUEST. The final steps used established ratings of selected studies and feedback from independent raters to 6) assess reliability and validity; 7) assess formatting and usability; and 8) finalize NUQUEST. Results NUQUEST is based on the Scottish Intercollegiate Guidelines Network checklists for randomized controlled trials, cohort studies, and case-control studies. Using a purposive sample of 45 studies representing the 3 study designs, interrater reliability was high (Cohen's κ: 0.73; 95% CI: 0.52, 0.93) across all tools and at least moderate for individual tools (range: 0.57–1.00). The use of a worksheet improved usability and consistency of overall interrater agreement across all study designs (40% without worksheet, 80%–100% with worksheet). When compared to published ratings, NUQUEST ratings for evaluated studies demonstrated high concurrent validity (93% perfect or near-perfect agreement). Where there was disagreement, the nutrition-specific component was a contributing factor in discerning exposure methodological issues. Conclusions NUQUEST integrates nutrition-specific criteria with generic criteria from assessment tools with demonstrated reliability and validity. NUQUEST represents a consistent and transparent approach for evaluating RoB issues related to dietary exposure assessment commonly encountered in human nutrition studies. [ABSTRACT FROM AUTHOR]

Background Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET). Objectives We aimed to determine whether vitamin K1 supplementation inhibits arterial calcification activity in individuals with diabetes mellitus. Methods This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K1 supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K1 supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta. Results In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K1 supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P  = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P  = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P  = 0.002). Conclusions In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis. This trial was registered at anzctr.org.au as ACTRN12616000024448. [ABSTRACT FROM AUTHOR]

Background: Quantitative evaluation of mitral regurgitation (MR) in hypertrophic cardiomyopathy (HCM) by cardiovascular magnetic resonance (CMR) relies on an indirect volumetric calculation. The aim of this study was to directly assess and quantify MR jets in patients with HCM using 4D flow CMR jet tracking in comparison to standard-of-care CMR indirect volumetric method. Methods: This retrospective study included patients with HCM undergoing 4D flow CMR. By the indirect volumetric method from CMR, MR volume was quantified as left ventricular stroke volume minus forward aortic volume. By 4D flow CMR direct jet tracking, multiplanar reformatted planes were positioned in the peak velocity of the MR jet during systole to calculate through-plane regurgitant flow. MR severity was collected for agreement analysis from a clinical echocardiograms performed within 1 month of CMR. Inter-method and inter-observer agreement were assessed by intraclass correlation coefficient (ICC), Bland–Altman analysis, and Cohen's kappa. Results: Thirty-seven patients with HCM were included. Direct jet tracking demonstrated good inter-method agreement of MR volume compared to the indirect volumetric method (ICC = 0.80, p = 0.004) and fair agreement of MR severity (kappa = 0.27, p = 0.03). Direct jet tracking showed higher agreement with echocardiography (kappa = 0.35, p = 0.04) than indirect volumetric method (kappa = 0.16, p = 0.35). Inter-observer reproducibility of indirect volumetric method components revealed the lowest reproducibility in end-systolic volume (ICC = 0.69, p = 0.15). Indirect volumetric method showed good agreement of MR volume (ICC = 0.80, p = 0.003) and fair agreement of MR severity (kappa = 0.38, p < 0.001). Direct jet tracking demonstrated (1) excellent inter-observer reproducibility of MR volume (ICC = 0.97, p < 0.001) and MR severity (kappa = 0.84, p < 0.001) and (2) excellent intra-observer reproducibility of MR volume (ICC = 0.98, p < 0.001) and MR severity (kappa = 0.88, p < 0.001). Conclusions: Quantifying MR and assessing MR severity by indirect volumetric method in HCM patients has limited inter-observer reproducibility. 4D flow CMR jet tracking is a potential alternative technique to directly quantify and assess MR severity with excellent inter- and intra-observer reproducibility and higher agreement with echocardiography in this population. [ABSTRACT FROM AUTHOR]

Background: Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). Methods: CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. Results: GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0–5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups. Conclusion: LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM. [ABSTRACT FROM AUTHOR]

Background Although most studies have reported unfavorable short-term effects of breastfeeding on early-childhood sleep-wake behaviors that potentially attenuate over time, findings have remained inconsistent. Objectives We assessed associations of breastfeeding with longitudinal day-, night-, and total-sleep trajectories and with sleep-wake behaviors in healthy infants and preschoolers. Methods Caregivers of naturally conceived, term, singleton infants (n  = 654) completed the Brief Infant Sleep Questionnaire (3, 6, 9, 12, 18, and 24 mo) and/or Children's Sleep Habits Questionnaire (54 mo), and provided information on their infants' breastfeeding status at 3 mo. Trajectory analyses derived 4 day- (n  = 243), 3 night- (n  = 248), and/or 4 total- (n  = 241) sleep trajectories, each differing in length of sleep duration (short/moderate/long) and variability (variable/consistent). Sleep-wake behaviors from 3 to 24 mo (day/night/total-sleep durations and duration/number of night awakenings) were also assessed for associations with breastfeeding. Results After adjusting for potential covariates, formula-fed infants, relative to fully breastfed (predominant or exclusive) infants, were significantly less likely to exhibit moderate (OR: 0.28; 95% CI: 0.11, 0.70) and long consistent (OR: 0.18; 95% CI: 0.07, 0.50) night-sleep trajectories and less likely to exhibit moderate (OR: 0.21; 95% CI: 0.07, 0.61) and long consistent (OR: 0.12; 95% CI: 0.04, 0.38) and long variable (OR: 0.16; 95% CI: 0.05, 0.56) total-sleep trajectories, instead of short variable night- and total-sleep trajectories. Partially breastfed infants did not differ from fully breastfed infants for both night- and total-sleep trajectories. No significant differences were found between all groups for day-sleep trajectories. Fully breastfed infants had longer night- (6, 9, 12, and 24 mo) and total- (3 and 12 mo) sleep durations than formula-fed infants, albeit a greater number of night awakenings (from 6 to 12 mo). Conclusions Despite more night awakenings, fully breastfed infants have overall longer night- and total-sleep durations (sleep trajectories) than formula-fed infants. [ABSTRACT FROM AUTHOR]

Background The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. Objectives We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. Methods MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann–Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. Results In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r  = 0.31) and cholecalciferol (r  = 0.45) groups (P  < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n  = 372 total) [placebo (n  = 188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n  = 184): from 222.3 to 419.3 μg/mmol creatinine; P  = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n  = 188) than in the cholecalciferol group (n  = 184) (placebo: 0.16 ± 0.92; cholecalciferol: −0.16 ± 1.06; P -difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g. lumbar spine BMD: β = −0.02 g · cm−2 · SD−1 increase in CTX; 95% CI: −0.027, −0.002 g · cm−2 · SD−1; P  = 0.02, n  = 283). Conclusions Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum. This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23. [ABSTRACT FROM AUTHOR]

Background Observed associations of high-protein diets with changes in insulin resistance are inconclusive. Objectives We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied. Methods Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst − EIRep)/EIEst] × 100% and [(PRep − PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger. Results Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger. Conclusions During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c. This trial was registered at clinicaltrials.gov as NCT01777893. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. Methods: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15–20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE −−); otherwise, the image was labeled equivocal (LGE + −). Results: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE −− slices had lower ECV than LGE + + (p = 0.01). Conclusions: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. Methods: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15–20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE −−); otherwise, the image was labeled equivocal (LGE + −). Results: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE −− slices had lower ECV than LGE + + (p = 0.01). Conclusions: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) is increasingly used in the evaluation of patients who are potential candidates for implantable cardioverter-defibrillator (ICD) therapy to assess left ventricular (LV) ejection fraction (LVEF), myocardial fibrosis, and etiology of cardiomyopathy. It is unclear whether CMR-derived strain measurements are predictive of appropriate shocks and death among patients who receive an ICD. We evaluated the prognostic value of LV strain parameters on feature-tracking (FT) CMR in patients who underwent subsequent ICD implant for primary or secondary prevention of sudden cardiac death. Methods: Consecutive patients from 2 Canadian tertiary care hospitals who underwent ICD implant and had a pre-implant CMR scan were included. Using FT-CMR, a single, blinded, reader measured LV global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain. Cox proportional hazards regression was performed to assess the associations between strain measurements and the primary composite endpoint of all-cause death or appropriate ICD shock that was independently ascertained. Results: Of 364 patients (mean 61 years, mean LVEF 32%), 64(17.6%) died and 118(32.4%) reached the primary endpoint over a median follow-up of 62 months. Univariate analyses showed significant associations between GLS, GCS, and GRS and appropriate ICD shocks or death (all p < 0.01). In multivariable Cox models incorporating LVEF, GLS remained an independent predictor of both the primary endpoint (HR 1.05 per 1% higher GLS, 95% CI 1.01–1.09, p = 0.010) and death alone (HR 1.06 per 1% higher GLS, 95% CI 1.02–1.11, p = 0.003). There was no significant interaction between GLS and indication for ICD implant, presence of ischemic heart disease or late gadolinium enhancement (all p > 0.30). Conclusions: GLS by FT-CMR is an independent predictor of appropriate shocks or mortality in ICD patients, beyond conventional prognosticators including LVEF. Further study is needed to elucidate the role of LV strain analysis to refine risk stratification in routine assessment of ICD treatment benefit. [ABSTRACT FROM AUTHOR]

Background Reports on the adequacy of vitamin D status of pregnant women are not available in Canada. Objectives The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada. Methods Pregnant women (≥18 years) from 6 provinces (2008–2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n  = 1905) and third trimesters (n  = 1649) and at delivery (n  = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test. Results In the first trimester, 93.4% (95% CI: 92.3%–94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P  < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25–0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42–3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02–1.89). Conclusions The results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women. [ABSTRACT FROM AUTHOR]

Background Elevated plasma methylmalonic acid (MMA) and/or total homocysteine (tHcy), as well as low serum vitamin B12 and/or holotranscobalamin (holoTC) are indicative of vitamin B12 deficiency. Combined indicators (cB12), which pool some or all 4 markers into an index, may be a more reliable diagnostic tool to overcome inconclusive diagnoses with individual markers. Objectives We aimed to describe different cB12 score combinations and estimate the prevalence of low or transitional vitamin B12 status compared with individual markers. Design Using cross-sectional data for B12, MMA, and tHcy in persons ≥20 y participating in NHANES 1999–2004 (n  = 12,335), we examined raw and covariate-adjusted regression models to assess determinants of 3cB12 (all 3 markers) and combinations of 2cB12 (2 markers). Results 3cB12 was significantly associated with B12 (Spearman r  = 0.75), MMA (r = −0.70), and tHcy (r = −0.59). The 3cB12 reference interval (2.5th to 97.5th percentile) was -0.538 to 1.60. In covariate-adjusted models, we found no association of 3cB12 with age; adult females and users of B12 supplements had higher, while adults with advanced chronic kidney disease had lower 3cB12 levels regardless of race-Hispanic origin group (self-reported). Only 2.7% of adults had low or transitional vitamin B12 status using the proposed cB12 cutoff of ≤−0.5, while the prevalence of low (or low-normal) status depended on the selected individual marker and its cutoff: 2.2% and 13% for B12 < 148 and 148–222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff (250–320 nmol/L); and 8.4% for tHcy > 13 µmol/L. The reference intervals for B12, MMA, and tHcy overlapped from the low (<−2.5) to the transitional (−2.5 to −0.5) and to the adequate (>−0.5) cB12 categories. Conclusions Vitamin B12 deficiency may be overestimated among US adults when individual, conventional markers are used. When only 2 markers are available, the combination of B12 and MMA provides results comparable to 3cB12. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is to introduce what affects the firm to diversify. This paper is based on an empirical analysis of a sample of 453 manufacturing companies in India. Jacquemin-Berry Entropy-Index measure has been used to measure diversification; whereas to determine the factors affecting diversification strategy, Panel Tobit Regression Analysis has been applied. The research findings indicate that firm-specific antecedents influence the decision to diversify. Corporate managers should follow a prudent behaviour while adopting strategic planning for the growth of the company. Managers should have to conduct proper statistical analyses to find out a firm's optimal level of corporate diversification for maximising the firm performance. [ABSTRACT FROM AUTHOR]