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Background: Pulmonary hypertension (PH) is a life-threatening. Differentiation pulmonary arterial hypertension (PAH) from pulmonary venous hypertension (PVH) is important due to distinct treatment protocols. Invasive right heart catheterization (RHC) remains the reference standard but noninvasive alternatives are needed., Purpose/hypothesis: To evaluate 4D Flow MRI-derived 3D vortex energetics in the left pulmonary artery (LPA) for distinguishing PAH from PVH., Study Type: Prospective case-control., Population/subjects: Fourteen PAH patients (11 female) and 18 PVH patients (9 female) diagnosed from RHC, 23 healthy controls (9 female)., Field Strength/sequence: 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession (bSSFP) cardiac cine sequences., Assessment: LPA 3D vortex cores were identified using the lambda2 method. Peak vortex-contained kinetic energy (vortex-KE) and viscous energy loss (vortex-EL) were computed from 4D flow MRI. Left and right ventricular (LV, RV) stroke volume (LVSV, RVSV) and ejection fraction (LVEF, RVEF) were computed from bSSFP. In PH patients, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWR) and pulmonary vascular resistance (PVR) were determined from RHC., Statistical Tests: Mann-Whitney U test for group comparisons, Spearman's rho for correlations, logistic regression for identifying predictors of PAH vs. PVH and develop models, area under the receiver operating characteristic curve (AUC) for model performance. Significance was set at P < 0.05., Results: PAH patients showed significantly lower vortex-KE (37.14 [14.68-78.52] vs. 76.48 [51.07-120.51]) and vortex-EL (9.93 [5.69-25.70] vs. 24.22 [12.20-32.01]) than PVH patients. The combined vortex-KE and LVEF model achieved an AUC of 0.89 for differentiating PAH from PVH. Vortex-EL showed significant negative correlations with mPAP (rho = -0.43), PCWP (rho = 0.37), PVR (rho = -0.64). In the PAH group, PVR was significantly negatively correlated with LPA vortex-KE (rho = -0.73) and vortex-EL (rho = -0.71), and vortex-KE significantly correlated with RVEF (rho = 0.69), RVSV, (rho = 0.70). In the PVH group, vortex-KE (rho = 0.52), vortex-EL significantly correlated with RVSV (rho = 0.58)., Data Conclusion: These preliminary findings suggest that 4D flow MRI-derived LPA vortex energetics have potential to noninvasively differentiate PAH from PVH and correlate with invasive hemodynamic parameters., Evidence Level: 1 TECHNICAL EFFICACY: Stage 3., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

To test the hypothesis that cine MRI-derived radiomics features of the cardiac blood pool can represent hemodynamic characteristics of pulmonary hypertension-heart failure with preserved ejection fraction (PH-HFpEF). Nineteen PH-HFpEF patients (9 male, 57.8 ± 14.7 years) and 19 healthy controls (13 male, 50.3 ± 13.6 years) were enrolled. All participants underwent a cardiac MRI scan. One hundred and seven radiomics features (7 classes) of the blood pool in the left and right ventricles/atrium (LV/RV/LA/RA) were extracted from 4-chamber cine (2D images) at the stages of systole, rapid filling, diastasis, and atrial contraction within a cardiac cycle. For PH-HFpEF patients, features acquired from LV/LA were related to the pulmonary capillary wedge pressure (PCWP); features acquired from RV/RA were related to the mean pulmonary artery pressure (mPAP) using the Pearson correlation coefficient (r). Logistic regression, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to test the capability of radiomics features in discriminating 2 subject groups. Features acquired from different chambers at various periods present diverse properties in representing hemodynamic indices of PH-HFpEF. Multiple radiomics features blood pool were significantly related to PCWP and/or mPAP (r: 0.4-0.679, p < 0.05). In addition, multiple features of blood pools acquired at various time points within a cardiac cycle can efficiently discriminate PH-HFpEF from controls (individual AUC: 0.7-0.864). Cine MRI-derived radiomics features of the cardiac blood pool have the potential to characterize hemodynamic abnormalities in the context of PH-HFpEF., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Although cine MRI-derived radiomics features in the cardiac blood pool have been used to represent cardiac function and motion, the clinical relevance of radiomics features in the great vessels is still unknown. The aim of the present study was to test the hypothesis that cine MRI-derived radiomics features of the pulmonary artery (PA) can represent hemodynamic abnormalities in pulmonary hypertension (PH). With the approval of the institutional review board (IRB), 50 PH patients (21 males, 36-89 years old, diagnosed with right heart catheterization [RHC]) and 23 healthy volunteers (14 males, 26-80 years old) were retrospectively enrolled in this study. All participants underwent cardiac 4D flow and cine MRI (25 retrospective phases) at the right ventricular (RV) outflow tract (RVOT). A total of 93 radiomics features were extracted from RVOT cine images through a fixed size region of interest (ROI) at the proximal part of the PA. The peak values of the 6 first order features were different between the PH patients and controls. 4D flow-derived mean velocity in PA was related to 'Kurtosis' (r = 0.452,), 'Range' (r = 0.426), 'Autocorrelation' (r = 0.407), 'Joint Average' (r = 0.459), 'Sum Average' (r = 0.459), 'High Gray Level Emphasis' (r = 0.41), 'Large Dependence High Gray Level Emphasis' (r = 0.44), 'High Gray Level Run Emphasis' (r = 0.422), 'Gray Level Variance' (r = 0.419), 'High Gray Level Zone Emphasis' (r = 0.451), and 'Small Area High Gray Level Emphasis' (r = 0.415). Mean RV pressure was related to 'Inverse Variance' (r = 0.43) and 'Run Percentage' (r = 0.403). All p values < 0.05. Cine MRI-derived PA radiomics features have the potential to serve as novel imaging biomarkers for representing hemodynamic changes in pulmonary circulation., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Although radiomics features of the left ventricular wall have been used to assess cardiac diseases, radiomics features of the cardiac blood pool have been relatively ignored., Purpose: To test the hypothesis that cine MRI-derived radiomics features of the cardiac blood pool are associated with cardiac function and motion., Study Type: Retrospective., Population: A total of 26 healthy volunteers (51.2 ± 15.6 years; 17 males)., Field Strength/sequence: A 1.5 T/balanced steady-state free precession (bSSFP)., Assessment: The radiomics features (107 features in seven classes) of the blood pool of the left/right ventricle/atrium (LV/RV/LA/RA) were extracted on four-chamber cine images (25 phases). Conventional cardiac function parameters (volumes, ejection fraction [EF] and longitudinal strain) were assessed in each cardiac chamber. Intraobserver- and interobserver agreements of radiomics features of all chambers acquired at all phases were assessed, as well as scan-rescan agreement in a subset of 13 volunteers., Statistical Tests: Pearson correlation coefficients (r) were used to assess the associations between peak values of radiomics features and end-diastolic (or maximal) volume, end-systolic (or minimal) volume, EF, and longitudinal strain of corresponding chambers. Good intraobserver, interobserver, and scan-rescan agreements for radiomics features acquired were defined as intraclass correlation coefficient (ICC) > 0.7 or coefficient of variation (CoV) < 20%., Results: Most radiomics features of the blood pool varied periodically throughout the cardiac cycle. Peak values of chamber-specific blood pool radiomics features were correlated with traditional cardiac function and motion indices of corresponding chambers (r: 0.4-0.87). Ninety-three (87%), 86 (80%), and 73 (68%) radiomics features demonstrated good intraobserver, interobserver, and scan-rescan reproducibility, respectively., Conclusion: Cine MRI-derived radiomics features within LV/RV/LA/RA are associated with traditional cardiac function and motion indices of corresponding chambers and may have the potential to become novel quantitative imaging biomarkers in cardiovascular medicine., Evidence Level: 3., Technical Efficacy: 1., (© 2022 International Society for Magnetic Resonance in Medicine.)

Aims: A shorter cardiac rest period within a cardiac cycle is usually thought to be a result of a fast heart rate, and its clinical relevance has long been ignored. The aim of the present study was to test the hypothesis that the length of cardiac rest periods is altered in postcapillary pulmonary hypertension (PH)., Methods and Results: Twenty-six patients with postcapillary PH and 20 healthy controls were recruited for cardiac magnetic resonance imaging (MRI) scans. All participants had a heart rate no higher than 80 beats/minute. Cine magnetic resonance imaging (MRI, acquired at a four-chamber view) was analyzed to determine the length of cardiac rest periods at end-systole and mid-to-late diastole. PH patients had a shorter rest period at mid-to-late diastole than controls (17.5 ± 8.7% vs. 24.2 ± 4.2%, P = 0.003). Receiver operating characteristic (ROC) curves showed that the proportion of the rest period in diastole (defined as the length of diastasis/diastole) can discriminate PH patients from controls [area under the curve (AUC) = 0.83, 95% confidence interval (CI): 0.71-0.96]. The existence of postcapillary PH was a significant contributor (β = -5.537, P = 0.023) to shorter cardiac rest periods at mid-to-late diastole after adjusting for potential confounders, including age, sex, heart rate, and blood pressure., Conclusions: Postcapillary PH is independently associated with shorter cardiac rest periods at mid-to-late diastole. The length of cardiac rest periods has the potential to become a novel quantitative imaging biomarker for indicating cardiovascular health., Competing Interests: Conflict of interest: This study was supported by Bayer Pharmaceutical. The grant was paid to the institution not to individual investigators. James C. Carr has disclosures: Siemens: research grant to institution; advisory board Bayer: research grant to institution; advisory board; speaker Bracco: advisory board Guerbet: research grant to institution No other authors have conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pulmonary hypertension (PH) contributes to restricted flow through the pulmonary circulation characterized by elevated mean pulmonary artery pressure acquired from invasive right heart catheterization (RHC). MRI may provide a noninvasive alternative for diagnosis and characterization of PH., Purpose: To characterize PH via quantification of regional pulmonary transit times (rPTT)., Study Type: Retrospective., Population: A total of 43 patients (58% female); 24 controls (33% female). RHC-confirmed patients classified as World Health Organization (WHO) subgroups 1-4., Field Strength/sequence: A 1.5 T/time-resolved contrast-enhanced MR Angiography (CE-MRA)., Assessment: CE-MRA data volumes were combined into a 4D matrix (3D resolution + time). Contrast agent arrival time was defined as the peak in the signal-intensity curve generated for each voxel. Average arrival times within a vessel region of interest (ROI) were normalized to the main pulmonary artery ROI (t 0 ) for eight regions to define rPTT for all subjects. Subgroup analysis included grouping the four arterial and four venous regions. Intraclass correlation analysis completed for reproducibility., Statistical Tests: Analysis of covariance with age as covariate. A priori Student's t-tests or Wilcoxon rank-sum test; α = 0.05. Results compared to controls unless noted. Significant without listing P value. ICC ran as two-way absolute agreement model with two observers., Results: PH patients demonstrated elevated rPTT in all vascular regions; average rPTT increase in arterial and venous branches was 0.85 ± 0.15 seconds (47.7%) and 1.0 ± 0.18 seconds (16.9%), respectively. Arterial rPTT was increased for all WHO subgroups; venous regions were elevated for subgroups 2 and 4 (group 1, P = 0.86; group 3, P = 0.32). No significant rPTT differences were found between subgroups (P = 0.094-0.94). Individual vessel ICC values ranged from 0.58 to 0.97., Data Conclusion: Noninvasive assessment of PH using standard-of-care time-resolved CE-MRA can detect increased rPTT in PH patients of varying phenotypes compared to controls., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: The aim of this study was to test the hypothesis that there are good agreements between cardiac functional and structural indices derived from magnetic resonance imaging (MRI) sequences triggered with pilot tone (PT) and electrocardiogram (ECG)., Materials and Methods: Sixteen healthy volunteers (11 male, age 21-76 years) underwent a cardiac MRI scan. Cine MRI, T1, and T2 mapping were acquired by using PT and ECG triggering. Quantitative measurements, including left and right ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, longitudinal strain, left ventricular T1 and T2 values, left and right atrial longitudinal strain, and maximal/minimal volumes, were measured. The interclass correlation coefficient, coefficient of variation, and Bland-Altman plots were used to evaluate the agreements between measurements derived by MRI sequences triggered with 2 methods., Results: There were no significant differences among end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, left ventricle mass, T1 and T2 values, or longitudinal strains acquired using PT and ECG. There were good agreements and low variations between the levels of these indices acquired with PT and ECG. Interclass correlation coefficients mainly ranged from 0.73 to 0.98. The coefficients of variation ranged from 1.4% to 22.6%., Conclusions: Pilot tone-triggered MRI provides comparable measurements of cardiac function, motion, and structure as ECG-triggered MRI. Pilot tone has the potential to become a backup of ECG gating in cardiovascular imaging., Competing Interests: Conflicts of interest and sources of funding: This study was supported by a grant from the National Institutes of Health (R01HL117888). J.C.C. has disclosures for Siemens (research grant to institution, advisory board), Bayer (research grant to institution, advisory board, speaker), Bracco (advisory board), Guerbet (research grant to institution); P.S. and C.H. are full-time employees of Siemens Healthcare GmbH. R.D. is a full-time employee of Siemens Medical Solutions USA. All other authors have no other disclosure., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiac magnetic resonance imaging (MRI) is emerging as an alternative to right heart catheterization for the evaluation of pulmonary hypertension (PH) patients. The aim of this study was to compare cardiac MRI-derived left ventricle fibrosis indices between pre-capillary PH (PrePH) and isolated post-capillary PH (IpcPH) patients and assess their associations with measures of ventricle function. Global and segmental late gadolinium enhancement (LGE), longitudinal relaxation time (native T1) maps, and extracellular volume fraction (ECV) were compared among healthy controls (N = 25; 37% female; 52 ± 13 years), PH patients (N = 48; 60% female; 60 ± 14 years), and PH subgroups (PrePH: N = 29; 65% female; 55 ± 12 years, IpcPH: N = 19; 53% female; 66 ± 13 years). Cardiac cine measured ejection fraction, end diastolic, and end systolic volumes and were assessed for correlations with fibrosis. LGE mural location was qualitatively assessed on a segmental basis for all subjects. PrePH patients had elevated (apical-, mid-antero-, and mid-infero) septal left ventricle native T1 values (1080 ± 74 ms, 1077 ± 39 ms, and 1082 ± 47 ms) compared to IpcPH patients (1028 ± 53 ms, 1046 ± 36 ms, 1051 ± 44 ms) (p < 0.05). PrePH had a higher amount of insertional point LGE (69%) and LGE patterns characteristic of non-vascular fibrosis (77%) compared to IpcPH (37% and 46%, respectively) (p < 0.05; p < 0.05). Assessment of global LGE, native T1, and ECV burdens did not show a statistically significant difference between PrePH (1.9 ± 2.7%, 1056.2 ± 36.3 ms, 31.2 ± 3.7%) and IpcPH (2.7 ± 2.7%, 1042.4 ± 28.1 ms, 30.7 ± 4.7%) (p = 0.102; p = 0.229 p = 0.756). Global native T1 and ECV were higher in patients (1050.9 ± 33.8 and 31.0 ± 4.1%) than controls (28.2 ± 3.7% and 1012.9 ± 29.4 ms) (p < 0.05). Cardiac MRI-based tissue characterization may augment understanding of cardiac involvement and become a tool to facilitate PH patient classification.

Background: Cardiac allograft vasculopathy (CAV) is a complication beyond the first-year post-heart transplantation (HTx). We aimed to test the utility of cardiac magnetic resonance (CMR) to detect functional/structural changes in HTx recipients with CAV., Methods: Seventy-seven prospectively recruited HTx recipients beyond the first-year post-HTx and 18 healthy controls underwent CMR, including cine imaging of ventricular function and T1- and T2-mapping to assess myocardial tissue changes. Data analysis included quantification of global cardiac function and regional T2, T1 and extracellular volume based on the 16-segment model. International Society for Heart and Lung Transplantation criteria was used to adjudicate CAV grade (0-3) based on coronary angiography., Results: The majority of HTx recipients (73%) presented with CAV (1: n = 42, 2/3: n = 14, 0: n = 21). Global and segmental T2 (49.5 ± 3.4 ms vs 50.6 ± 3.4 ms, p < 0.001;16/16 segments) were significantly elevated in CAV-0 compared to controls. When comparing CAV-2/3 to CAV-1, global and segmental T2 were significantly increased (53.6 ± 3.2 ms vs. 50.6 ± 2.9 ms, p < 0.001; 16/16 segments) and left ventricular ejection fraction was significantly decreased (54 ± 9% vs. 59 ± 9%, p < 0.05). No global, structural, or functional differences were seen between CAV-0 and CAV-1., Conclusions: Transplanted hearts display functional and structural alteration compared to native hearts, even in those without evidence of macrovasculopathy (CAV-0). In addition, CMR tissue parameters were sensitive to changes in CAV-1 vs. 2/3 (mild vs. moderate/severe). Further studies are warranted to evaluate the diagnostic value of CMR for the detection and classification of CAV., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2022 Korean Society of Echocardiography.)

Background: Cardiac magnetic resonance imaging (MRI) is becoming an alternative to right heart catheterization (RHC) for evaluating pulmonary hypertension (PH). A need exists to further evaluate cardiac MRI's ability to characterize PH., Purpose: To evaluate the potential for four-dimensional (4D) flow MRI-derived pulmonary artery velocities to characterize PH., Study Type: Prospective case-control., Population: Fifty-four PH patients (56% female); 25 controls (36% female)., Field Strength/sequence: 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession cardiac cine., Assessment: RHC was used to derive patients' pulmonary vascular resistance (PVR). 4D flow measured blood velocities at the main, left, and right pulmonary arteries (MPA, LPA, and RPA); cine measured ejection fraction, end diastolic, and end systolic volumes (EF, EDV, and ESV). EDV and ESV were normalized (indexed) to body surface area (ESVI and EDVI). Parameters were evaluated between, and within, PH subgroups: pulmonary arterial hypertension (PAH); PH due to left heart disease (PH-LHD)/chronic lung disease (PH-CLD)/or chronic thrombo-emboli (CTE-PH)., Statistical Tests: Analysis of variance and Kruskal-Wallis tests compared parameters between subgroups. Pearson's r assessed velocity, PVR, and volume correlations. Significance definition: P < 0.05., Results: PAH peak and mean velocities were significantly lower than in controls at the LPA (36 ± 12 cm/second and 20 ± 4 cm/second vs. 59 ± 15 cm/second and 32 ± 9 cm/second). At the RPA, mean velocities were significantly lower in PAH vs. controls (27 ± 6 cm/second vs. 40 ± 9 cm/second). Peak velocities significantly correlated with right ventricular EF at the MPA (r = 0.286), RPA (r = 0.400), and LPA (r = 0.401). Peak velocity significantly correlated with right ventricular ESVI at the RPA (r = -0.355) and LPA (r = -0.316). Significant correlations between peak velocities and PVR were moderate at the LPA in PAH (r = -0.641) and in PH-LHD (r = -0.606) patients, and at the MPA in PH-CLD (r = -0.728). CTE-PH showed non-significant correlations between peak velocity and PVR at all locations., Data Conclusion: Preliminary findings suggest 4D flow can identify PAH and track PVR changes., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 5., (© 2021 International Society for Magnetic Resonance in Medicine.)

Competing Interests: J.C.C.: Bayer (Speaking/Teaching) (Advisory board), Guerbet, Siemens (Board Membership). M.M.: Circle Cardiovascular Imaging (Consulting), Cryolife Inc., Siemens Healthineers. The remaining authors declare no conflicts of interest.

Tissue phase mapping (TPM) is an MRI technique for quantification of regional biventricular myocardial velocities. Despite its potential, clinical use is limited due to the requisite labor-intensive manual segmentation of cardiac contours for all time frames. The purpose of this study was to develop a deep learning (DL) network for automated segmentation of TPM images, without significant loss in segmentation and myocardial velocity quantification accuracy compared with manual segmentation. We implemented a multi-channel 3D (three dimensional; 2D + time) dense U-Net that trained on magnitude and phase images and combined cross-entropy, Dice, and Hausdorff distance loss terms to improve the segmentation accuracy and suppress unnatural boundaries. The dense U-Net was trained and tested with 150 multi-slice, multi-phase TPM scans (114 scans for training, 36 for testing) from 99 heart transplant patients (44 females, 1-4 scans/patient), where the magnitude and velocity-encoded (V x , V y , V z ) images were used as input and the corresponding manual segmentation masks were used as reference. The accuracy of DL segmentation was evaluated using quantitative metrics (Dice scores, Hausdorff distance) and linear regression and Bland-Altman analyses on the resulting peak radial and longitudinal velocities (V r and V z ). The mean segmentation time was about 2 h per patient for manual and 1.9 ± 0.3 s for DL. Our network produced good accuracy (median Dice = 0.85 for left ventricle (LV), 0.64 for right ventricle (RV), Hausdorff distance = 3.17 pixels) compared with manual segmentation. Peak V r and V z measured from manual and DL segmentations were strongly correlated (R ≥ 0.88) and in good agreement with manual analysis (mean difference and limits of agreement for V z and V r were -0.05 ± 0.98 cm/s and -0.06 ± 1.18 cm/s for LV, and -0.21 ± 2.33 cm/s and 0.46 ± 4.00 cm/s for RV, respectively). The proposed multi-channel 3D dense U-Net was capable of reducing the segmentation time by 3,600-fold, without significant loss in accuracy in tissue velocity measurements., (© 2021 John Wiley & Sons, Ltd.)

Background: Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI)., Methods: We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline ( N =140) and 12-month change ( N =112) in cMRI parameters., Results: Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m 2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, β estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio ( β estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses., Conclusions: Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter., Competing Interests: G.A. Block reports receiving research funding from Akebia, Ardelyx, and GlaxoSmithKline; having consultancy agreements with Akebia, Keryx, Kirin, and Reata; receiving honoraria from Amgen and Kirin; serving as a scientific advisor for or member of Ardelyx, CJASN, Kirin, and Reata; having ownership interest in Ardelyx and Reata; and having other interests in/relationships with DaVita (previously medical director), Kidney Disease Improving Global Outcomes (previously on Executive Commitee), and Reata (previous employment). J. Carr reports serving on a speakers bureau for Bayer; receiving honoraria from Bayer, Bracco, and Guerbet; having consultancy agreements with Bayer, Bracco, and Siemens; receiving research funding from Bayer, Guerbet, and Siemens; and serving as a scientific advisor for or member of the Society for Cardiovascular MRI. A.K. Cheung reports having consultancy agreements with, and receiving honoraria from, Boehringer Ingelheim, Calliditas, and UptoDate; serving as a scientific advisor for or member of Hong Kong Journal of Nephrology, JASN, and Kidney Diseases; having other interests in/relationships with KDIGO; and having ownership interest in Merck. M. Chonchol reports having consultancy agreements with Amgen, Corvidia, Otsuka, Reata, Tricidia, and Vifor; receiving honoraria from Amgen, Corvidia, Reata, Tricidia, and Vifor; serving as a scientific advisor for or member of the CJASN editorial board; and receiving research funding from the Corvidia, National Institutes of Health (NIH), Otsuka, Reata, and Sanofi. L.F. Fried reports having consultancy agreements with Bayer, and serving on data safety monitoring boards for CSL Behring and Novo Nordisk. J.J. Gassman reports having consultancy agreements with, and receiving honoraria from, the Baim Institute (Harvard Clinical Research Institute). T. Isakova reports having consultancy agreements with, and receiving honoraria from, Akebia Therapeutics Inc.; and serving as an associate editor of American Journal of Kidney Diseases. J.H. Ix reports serving as a scientific advisor for or member of AlphaYoung; having consultancy agreements with Ardelyx, AstraZeneca, Bayer, Jnana, and Sanifit; and receiving research funding from Baxter International. R. Mehta reports having ownership interest in AbbVie Inc.; having consultancy agreements with, and receiving honoraria from, Akebia/Otsuka and AstraZeneca; and serving on the editorial board of the Journal of Cardiac Failure. J.P. Middleton reports serving on the editorial board for Advances in Chronic Kidney Disease and on a data safety monitoring board for the NIDDK; having consultancy agreements with AstraZeneca and Vifor/Relypsa; receiving research funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Vifor/Relypsa; having other interests in/relationships with Raleigh Radiology (via spouse); and receiving honoraria from Relypsa/Vifor. D.S. Raj reports having other interests in/relationships with the American Association of Kidney Patients; serving as a scientific advisor for or member of the National Heart, Lung, and Blood Institute (NHLBI), NIDDK, and Novo Nordisk; receiving research funding from NIH; and having consultancy agreements with, and receiving honoraria from, Novo Nordisk. K.L. Raphael reports having consultancy agreements with AstraZeneca. S.M. Sprague reports serving as a scientific advisor for or member of the American Association of Endocrine Surgeons American Journal of Nephrology, International Federation of Clinical Chemistry and Laboratory Medicine Work Group for Parathyroid Hormone, and National Kidney Foundation of Illinois; having consultancy agreements with Amgen, Ardelyx, Fresenius, Horizon, Litholink Corp., OPKO, Shire, and Vifor; receiving research funding from Amgen, Ardelyx, OPKO, and Reata; receiving honoraria from Amgen, Ardelyx, Fresenius, Horizon, OPKO, and Vifor; serving on speakers bureaus for Amgen, Fresenius, Horizon, and OPKO; and having ownership interest via individually owned stocks in Apple, Bristol Myers, Coca Cola, First Australia Fund, IBM, Paycheck, US Concrete, and Walgreens. A. Srivastava reports serving on a speaker’s bureau for AstraZeneca; receiving honoraria from AstraZeneca, Bayer, and Horizon Therapeutics PLC; and having consultancy agreements with CVS Caremark and Tate & Latham (medicolegal consulting). M. Wolf reports having consultancy agreements with, and receiving honoraria from, Akebia, Amgen, Ardelyx, AstraZeneca, Bayer, Pharmacosmos, Unicycive, and Walden; and having ownership interest in, and serving as a scientific advisor for or member of, Akebia, Unicycive, and Walden. All remaining authors have nothing to disclose.All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Cine magnetic resonance imaging (MRI) is an emerging modality for evaluating left ventricular (LV) motion/deformation patterns, which may have potential to identify LV dysfunctions underlying postcapillary pulmonary hypertension (PH). The aim of this study was to test the hypothesis that cine MRI-derived LV motion/deformation indices can be used to identify an elevated left heart pressure in PH. This was a retrospective study, which included 26 precapillary and 28 postcapillary PH patients (23 males, 58.9 ± 13.5 years old). All patients underwent right heart catheterization (the "reference standard") and cardiac MRI. Balanced steady-state free precession cine sequence acquired at 1.5 T was used. Cine MRI datasets were analyzed by using heart deformation analysis. LV motion/deformation indices were measured through 25 phases within a cardiac cycle. Peak LV displacement, velocity, strain, and strain rates at systole, early and late diastole were compared between the two patient groups using t-tests. The Pearson correlation coefficient (r) was used to investigate the association between cine MRI-derived indices and pulmonary capillary wedge pressure (PCWP). Multivariable linear and logistic regression models were applied to assess the ability of MRI-derived parameters to predict PCWP and postcapillary PH. Compared to 26 precapillary PH patients, the 28 postcapillary PH patients had lower peak late radial diastolic displacement (0.43 ± 0.19 cm vs. 0.64 ± 0.18 cm) and velocity (12.2 ± 5.8 mm/s vs. 18.9 ± 5.6 mm/s) and peak late radial (52.1 ± 32.7%/s vs. 97.1 ± 38%/s) and circumferential (38 ± 19.8%/s vs. 63.1 ± 22.9%/s) strain rates. PCWP was correlated with peak late radial diastolic displacement (r = -0.54) and velocity (r = -0.57) and peak late radial (r = -0.63) and circumferential diastolic (r = -0.63) strain rates. Peak late radial strain rate could predict PCWP (β = -0.09) and postcapillary PH (β = -0.036). All p < 0.05. Cine MRI-derived LV late diastolic motion/deformation properties can be used to estimate elevated left heart pressure in PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To test the hypothesis that cine MRI can be used to characterize features of left and right ventricles in post-capillary pulmonary hypertension (PH) caused by heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)., Methods: With the approval of institution review board (IRB), 28 consecutive post-capillary PH patients (11 males, 62.1 ± 13.4 years old, range 39-89 years old) underwent cine MRI scans. Cine MRI-derived left ventricular (LV) ejection fraction (LVEF) and other function, motion, and deformation indices (acquired with heart deformation analysis [HDA]) were compared between PH-HFpEF (defined as LVEF ≥ 50 %]) and PH-HFrEF (LVEF < 50 %) patients and were related with right ventricular (RV) indices and right heart catheterization (RHC)-derived pulmonary artery measurements., Results: Totally 19 patients (68 %, 95 % confident interval [CI] 49 %-86 %) were assigned to PH-HFpEF group while 9 (32 %) was assigned to the PH-HFrEF group. There were differences of LV and right ventricular (RV) global functional indices, LV mass, LV displacement, velocity, strain and strain rate between the two patient groups. Cine MRI-derived LV indices had broad associations with RV indices and RHC measurements. LVEF was negatively correlated with pulmonary capillary wedge pressure (PCWP) (r = -0.5, p = 0.007). LV cardiac index (LVCI) was associated with systolic pulmonary artery pressure (sPAP) (r = 0.443, p = 0.018)., Conclusions: PH-HFpEF and PH-HFrEF patients present dissimilar function, motion and deformation features in LV and RV. Cine MRI-derived LV measures are correlated with hemodynamic abnormalities of PH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods. In this position paper, we review current authoritative statements and suggest a novel alternative: screening MRI (s-MRI), supported by evidence from a preliminary population-based study (completed in 2018), and a prospective, controlled study in military recruits (in development). We present: 1. Literature-Based Comparisons (for diagnosing hr-CVCs): Two recent studies using traditional methods to identify hr-CVCs in >3,000 young athletes are compared with our s-MRI-based study of 5,169 adolescents. 2. Critical Review of Previous Results: The reported incidence of SCD in athletes is presently based on retrospective, observational, and incomplete studies. H&P's screening value seems minimal for structural heart disease, versus echocardiography (which improves diagnosis for high-risk cardiomyopathies) and s-MRI (which also identifies high-risk coronary artery anomalies). Electrocardiography is valuable in screening for potentially high-risk electrophysiological anomalies. 3. Proposed Project : We propose a prospective, controlled study (2 comparable large cohorts: one historical, one prospective) to compare: (1) diagnostic accuracy and resulting mortality-prevention performance of traditional screening methods versus questionnaire/electrocardiography/s-MRI, during 2-month periods of intense, structured exercise (in military recruits, in advanced state of preparation); (2) global costs and cost/efficiency between these two methods. This study should contribute significantly toward a comprehensive understanding of the incidence and causes of exercise-related mortality (including establishing a definition of hr-CVCs) while aiming to reduce mortality., Competing Interests: The authors report no relationships that could be construed as a conflict of interest., (© 2021 Published by Elsevier B.V.)

Background: Cardiac MRI is an emerging modality for evaluating left ventricular (LV) diastolic dysfunction (LVDD), a pathological condition that is prevalent in aging populations. However, there is a lack of reports of MRI-derived LV diastolic properties in late diastole., Purpose: To test the hypothesis that cine MRI-derived motion/deformation indices can be used to characterize age-related changes on LV relaxation patterns in late diastole., Study Type: Retrospective., Population: In all, 412 participants (72.5 ± 4.6 years old, range 65-84) without a documented history of cardiovascular diseases., Field Strength/sequence: Balanced steady-state free precession(bSSFP) acquired at 1.5T., Assessment: Participants were divided into younger (65-74 years old, n = 275) and older (75-84 years old, n = 137) groups. Status of diabetes mellitus (DM), hypertension (HTN), and lipid disorders were recorded for each participant. Cine MRI datasets were analyzed by using heart deformation analysis (HDA). LV motion/deformation indices (displacement, velocity, strain, and strain rate) were measured through 22 phases within a cardiac cycle., Statistical Tests: The prevalence of traditional cardiovascular risk conditions, LV ejection fraction (LVEF), peak LV regional displacement, velocity, and strain rates at early and late diastole were compared between two participant groups using chi-square tests or t-tests., Results: Older participants had a significantly lower peak early radial displacement (0.797 ± 0.249 cm vs. 0.876 ± 0.286 cm), radial velocity (19.3 ± 6.3 mm/s vs. 17.5 ± 5.2 mm/s), and circumferential strain rate (64.6 ± 15.7%/s vs. 70.1 ± 17%/s) but a higher peak late circumferential strain rate (69.8 ± 16.3 %/s vs. 66 ± 15.8 %/s) than their younger counterparts., Data Conclusion: Cine MRI can be used to characterize age-related LV relaxation patterns in late diastole., Level of Evidence: 3., Technical Efficacy Stage: 1., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Four-dimensional (D) flow magnetic resonance imaging (MRI) is limited by time-consuming and nonstandardized data analysis. We aimed to test the efficiency and interobserver reproducibility of a dedicated 4D flow MRI analysis workflow., Materials and Methods: Thirty retrospectively identified patients with bicuspid aortic valve (BAV, age=47.8±11.8 y, 9 male) and 30 healthy controls (age=48.8±12.5 y, 21 male) underwent Aortic 4D flow MRI using 1.5 and 3 T MRI systems. Two independent readers performed 4D flow analysis on a dedicated workstation including preprocessing, aorta segmentation, and placement of four 2D planes throughout the aorta for quantification of net flow, peak velocity, and regurgitant fraction. 3D flow visualization using streamlines was used to grade aortic valve outflow jets and extent of helical flow., Results: 4D flow analysis workflow time for both observers: 5.0±1.4 minutes per case (range=3 to 10 min). Valve outflow jets and flow derangement was visible in all 30 BAV patients (both observers). Net flow, peak velocity, and regurgitant fraction was significantly elevated in BAV patients compared with controls except for regurgitant fraction in plane 4 (91.1±29.7 vs. 62.6±19.6 mL/s, 37.1% difference; 121.7±49.7 vs. 90.9±26.4 cm/s, 28.9% difference; 9.3±10.1% vs. 2.0±3.4%, 128.0% difference, respectively; P<0.001). Excellent intraclass correlation coefficient agreement for net flow: 0.979, peak velocity: 0.931, and regurgitant fraction: 0.928., Conclusion: Our study demonstrates the potential of an efficient data analysis workflow to perform standardized 4D flow MRI processing in under 10 minutes and with good-to-excellent reproducibility for flow and velocity quantification in the thoracic aorta., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Magnetic resonance tissue phase mapping (TPM) measures three-directional myocardial velocities of the left and right ventricle (LV, RV). This noninvasive technique may supplement endomyocardial biopsy (EMB) in monitoring grafts post-heart transplantation (HTx)., Purpose: To assess biventricular myocardial velocity alterations in grafts and investigate the relationship between velocities and acute cellular rejection (ACR) episodes., Study Type: Prospective., Subjects: Twenty-seven patients within 1 year post-HTx (49 ± 13 years, 19 M) and 18 age-matched controls (49 ± 15 years, 12 M)., Field Strength/sequence: 1.5T, 2D balanced steady-state free precession, and TPM., Assessment: Ventricular function: end-diastolic and end-systolic volumes, stroke volumes, ejection fraction (EF), and myocardial mass. TPM velocities: peak-systolic and peak-diastolic velocities, cardiac twist, and interventricular dyssynchrony. ACR rejection episodes: International Society for Heart and Lung Transplantation grading of EMB specimens., Statistical Tests: The Lilliefors test for normality, unpaired t-tests, and Wilcoxon rank-sum tests for normally and nonnormally distributed data, respectively, were used, as well as multivariate regression for confounding variables and Pearson's correlation for associations between TPM velocities and global function., Results: Compared to controls, HTx patients demonstrated reduced biventricular systolic longitudinal velocities (LV: 5.2 ± 2.1 vs. 4.0 ± 1.5 cm/s, P < 0.05; RV: 4.2 ± 1.3 vs. 3.1 ± 1.2 cm/s, P < 0.01). Correlation analysis revealed significant positive relationships for biventricular EF with radial peak velocities of the same ventricle in both systole and diastole (LV systole: r = 0.48, P < 0.01; LV diastole: r = 0.28, P < 0.05; RV systole: r = 0.35, P < 0.01; RV diastole: r = 0.36, P < 0.01). Segmentally, longitudinal velocities were impaired in 7/16 LV segments and 5/10 RV segments in systole and 7/10 RV segments in diastole. TPM analysis in studies with >4 preceding ACR episodes showed globally reduced RV and LV systolic radial velocity, and segmentally reduced radial and longitudinal systolic velocities., Data Conclusion: Biventricular global and segmental velocities were reduced in HTx patients. Patients with >4 rejection episodes showed reduced myocardial velocities. The TPM sequence may add functional information for monitoring graft dysfunction., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:920-929., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objectives: The purpose of this study was to examine prognostic value of T1- and T2-mapping techniques in heart transplant patients., Background: Myocardial characterization using T2 mapping (evaluation of edema/inflammation) and pre- and post-gadolinium contrast T1 mapping (calculation of extracellular volume fraction [ECV] for assessment of interstitial expansion/fibrosis) are emerging modalities that have been investigated in various cardiomyopathies., Methods: A total of 99 heart transplant patients underwent the magnetic resonance imaging (MRI) scans including T1- (n = 90) and T2-mapping (n = 79) techniques. Relevant clinical characteristics, MRI parameters including late gadolinium enhancement (LGE), and invasive hemodynamics were collected. Median clinical follow-up duration after the baseline scan was 2.4 to 3.5 years. Clinical outcomes include cardiac events (cardiac death, myocardial infarction, coronary revascularization, and heart failure hospitalization), noncardiac death and noncardiac hospitalization., Results: Overall, the global native T1, postcontrast T1, ECV, and T2 were 1,030 ± 56 ms, 458 ± 84 ms, 27 ± 4% and 50 ± 4 ms, respectively. Top-tercile-range ECV (ECV >29%) independently predicted adverse clinical outcomes compared with bottom-tercile-range ECV (ECV <25%) (hazard ratio [HR]: 2.87; 95% confidence interval [CI]: 1.07 to 7.68; p = 0.04) in a multivariable model with left ventricular end-systolic volume and LGE. Higher T2 (T2 ≥50.2 ms) independently predicted adverse clinical outcomes (HR: 3.01; 95% CI: 1.39 to 6.54; p = 0.005) after adjustment for left ventricular ejection fraction, left ventricular end-systolic volume, and LGE. Additionally, higher T2 (T2 ≥50.2 ms) also independently predicted cardiac events (HR: 4.92; CI: 1.60 to 15.14; p = 0.005) in a multivariable model with left ventricular ejection fraction., Conclusions: MRI-derived myocardial ECV and T2 mapping in heart transplant patients were independently associated with cardiac and noncardiac outcomes. Our findings highlight the need for larger prospective studies., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac MRI (CMR) techniques offer non-invasive visualizations of cardiac morphology and function. However, imaging can be time-consuming and complex. Seismocardiography (SCG) measures physical vibrations transmitted through the chest from the beating heart and pulsatile blood flow. SCG signals can be acquired quickly and easily, with inexpensive electronics. This study investigates relationships between CMR metrics of function and SCG signal features. Same-day CMR and SCG data were collected from 28 healthy adults and 6 subjects with aortic valve disease history. Correlation testing and statistical median/decile calculations were performed with data from the healthy cohort. MR-quantified flow and function parameters in the healthy cohort correlated with particular SCG energy levels, such as peak aortic velocity with low-frequency SCG (coefficient 0.43, significance 0.02) and peak flow with high-frequency SCG (coefficient 0.40, significance 0.03). Valve disease-induced flow abnormalities in patients were visualized with MRI, and corresponding abnormalities in SCG signals were identified. This investigation found significant cross-modality correlations in cardiac function metrics and SCG signals features from healthy subjects. Additionally, through comparison to normative ranges from healthy subjects, it observed correspondences between pathological flow and abnormal SCG. This may support development of an easy clinical test used to identify potential aortic flow abnormalities.

Purpose: To use structure-function cardiac MRI in the evaluation of relationships between donor and heart transplantation (HTx) recipient characteristics and changes in cardiac tissue structure and function. HTx candidates and donor hearts are evaluated for donor-recipient matches to improve survival, but the impact of donor and recipient characteristics on changes in myocardial tissue and function in the transplanted heart is not fully understood., Materials and Methods: Cardiac MRI at 1.5 T was performed from August 2014 to June 2017 in 58 HTx recipients (mean age, 51.1 years ± 12.6 [standard deviation], 26 female patients) and included T2 mapping (to evaluate edematous and/or inflammatory changes), precontrast and postcontrast T1 mapping (allowing the calculation of extracellular volume fraction [ECV] to estimate interstitial expansion), and tissue phase mapping (allowing the calculation of myocardial velocities and twist). Donor and recipient demographics (age, sex, height, weight, and body mass index [BMI]) and comorbidities (hypertension, diabetes, and smoking history) were evaluated for relationships with cardiac MRI measures., Results: Sex-influenced cardiac MRI measures of myocardial tissue and function are as follows: Female HTx recipients demonstrated increased precontrast T1 ( P = .002) and reduced systolic peak long-axis velocities ( P = .015). Increased age of the donor heart was associated with elevated T2 ( r = 0.32; P < .05) and ECV ( r = 0.47; P < .01), indicating increased edema and interstitial expansion, as well as impaired diastolic peak long-axis velocities ( r = 0.41; P < .01). Recipient-donor differences in age, weight, and BMI were significantly associated with elevated ECV ( r = 0.36-0.48; P < .05). Hypertension in donors resulted in increased ECV (31.0% ± 4.2 vs 26.0% ± 3.3; P = .001)., Conclusion: Donor and HTx recipient characteristics were significantly associated with cardiac MRI-derived measures of myocardial tissue structure and function.© RSNA, 2019., (2019 by the Radiological Society of North America, Inc.)

The assessment of both left (LV) and right ventricular (RV) motion is important to understand the impact of heart disease on cardiac function. The MRI technique of tissue phase mapping (TPM) allows for the quantification of regional biventricular three-directional myocardial velocities. The goal of this study was to establish normal LV and RV velocity parameters across a wide range of pediatric to adult ages and to investigate the feasibility of TPM for detecting impaired regional biventricular function in patients with repaired tetralogy of Fallot (TOF). Thirty-six healthy controls (age = 1-75 years) and 12 TOF patients (age = 5-23 years) underwent cardiac MRI including TPM in short-axis locations (base, mid, apex). For ten adults, a second TPM scan was used to assess test-retest reproducibility. Data analysis included the calculation of biventricular radial, circumferential, and long-axis velocity components, quantification of systolic and diastolic peak velocities in an extended 16 + 10 LV + RV segment model, and assessment of inter-ventricular dyssynchrony. Biventricular velocities showed good test-retest reproducibility (mean bias ≤ 0.23 cm/s). Diastolic radial and long-axis peak velocities for LV and RV were significantly reduced in adults compared to children (19-61%, p < 0.001-0.02). In TOF patients, TPM identified significantly reduced systolic and diastolic LV and RV long-axis peak velocities (20-50%, p < 0.001-0.05) compared to age-matched controls. In conclusion, tissue phase mapping enables comprehensive analysis of global and regional biventricular myocardial motion. Changes in myocardial velocities associated with age underline the importance of age-matched controls. This pilot study in TOF patients shows the feasibility to detect regionally abnormal LV and RV motion.

Purpose: To evaluate the utility of cardiac magnetic resonance (CMR) T1 mapping in early systemic sclerosis (SSc) and its association with skin score., Methods: Twenty-four consecutive patients with early SSc referred for cardiovascular evaluation and 12 controls without SSc were evaluated. All patients underwent cine, T1 mapping, and late gadolinium enhanced (LGE) CMR imaging. T1 mapping indices were compared between SSc patients and controls (extracellular volume fraction [ECV], gadolinium partition coefficient [λ], pre-contrast T1, and post-contrast T1). The association between T1 mapping parameters and the modified Rodnan skin score (mRSS) was determined., Results: There were no significant differences in cardiac structure/function between SSc patients and controls on cine imaging, and 8/24 (33%) SSc patients had evidence of LGE (i.e., focal myocardial fibrosis). Of the T1 mapping parameters (indices indicative of diffuse myocardial fibrosis), ECV differentiated SSc patients from controls the best, followed by λ, even when the eight SSc patients with LGE were excluded. ECV had a sensitivity and specificity of 75% and 75% for diffuse myocardial fibrosis (optimal abnormal cut-off value of >27% [area under ROC curve=0.85]). In the 16 patients without evidence of LGE, each of the 4 CMR T1 mapping parameters (ECV, λ, Pre-T1 and Post-T1) correlated with mRSS (R=0.51-0.65, P=0.007-0.043), indicating a correlation between SSc cardiac and skin fibrosis., Conclusions: The four T1 mapping indices are significantly correlated with mRSS in patients with early SSc. Quantification of diffuse myocardial fibrosis using ECV should be considered as a marker for cardiac involvement in SSc clinical studies., Competing Interests: Conflict of interest DL (research grant – Abbott Laboratories; advising, consulting –Gilead Sciences, Inc); MH (consulting – Bayer HealthCare Pharmaceuticals, Inc, Sanofi Aventis Pharmaceuticals); JV (advising, consulting -Amira Pharmaceuticals); JCC (advising, consulting - Astellas Pharma, Inc., Bayer HealthCare Pharmaceuticals, Inc., Lantheus Medical Imaging, Inc.) RS, MMS, AA, BCB, AT, KK, JL, MC, KA and SJS declare no competing interests

In vitro studies suggested that glucose metabolism through the oxidative pentose phosphate pathway (oxPPP) can paradoxically feed superoxide-generating enzymes in failing hearts. We therefore tested the hypothesis that acute inhibition of the oxPPP reduces oxidative stress and enhances function and metabolism of the failing heart, in vivo. In 10 chronically instrumented dogs, congestive heart failure (HF) was induced by high-frequency cardiac pacing. Myocardial glucose consumption was enhanced by raising arterial glycemia to levels mimicking postprandial peaks, before and after intravenous administration of the oxPPP inhibitor 6-aminonicotinamide (80 mg/kg). Myocardial energy substrate metabolism was measured with radiolabeled glucose and oleic acid, and cardiac 8-isoprostane output was used as an index of oxidative stress. A group of five chronically instrumented, normal dogs served as control. In HF, raising glycemic levels from ∼ 80 to ∼ 170 mg/dL increased cardiac isoprostane output by approximately twofold, whereas oxPPP inhibition normalized oxidative stress and enhanced cardiac oxygen consumption, glucose oxidation, and stroke work. In normal hearts glucose infusion did not induce significant changes in cardiac oxidative stress. Myocardial tissue concentration of 6P-gluconate, an intermediate metabolite of the oxPPP, was significantly reduced by ∼ 50% in treated versus nontreated failing hearts, supporting the inhibitory effect of 6-aminonicotinamide. Our study indicates an important contribution of the oxPPP activity to cardiac oxidative stress in HF, which is particularly pronounced during common physiological changes such as postprandial glycemic peaks.

The effects of vagal stimulation (VS) on cardiac energy substrate metabolism are unknown. We tested the hypothesis that acute VS alters the balance between free fatty acid (FFA) and carbohydrate oxidation and opposes the metabolic effects of β-adrenergic stimulation. A clinical-type selective stimulator of the vagal efferent fibres was connected to the intact right vagus in chronically instrumented dogs. VS was set to reduce heart rate by 30 beats min(-1), and the confounding effects of bradycardia were then eliminated by pacing the heart at 165 beats min(-1). [(3)H]Oleate and [(14)C]glucose were infused to measure FFA and glucose oxidation. The heart was subjected to β-adrenergic stress by infusing dobutamine at 5, 10 and 15 μg kg(-1) min(-1) before and during VS. VS did not significantly affect baseline cardiac performance, haemodynamics or myocardial metabolism. However, at peak dobutamine stress, VS attenuated the increase in left ventricular pressure-diameter area from 235.9 ± 72.8 to 167.3 ± 55.8%, and in cardiac oxygen consumption from 173.9 ± 23.3 to 127.89 ± 6.2% (both P < 0.05), and thus mechanical efficiency was not enhanced. The increase in glucose oxidation fell from 289.3 ± 55.5 to 131.1 ± 20.9% (P < 0.05), while FFA oxidation was not increased by β-adrenergic stress and fell below baseline during VS only at the lowest dose of dobutamine. The functional and in part the metabolic changes were reversed by 0.1 mg kg(-1) atropine i.v. Our data show that acute right VS does not affect baseline cardiac metabolism, but attenuates myocardial oxygen consumption and glucose oxidation in response to adrenergic stress, thus functioning as a cardio-selective antagonist to β-adrenergic activation.

Background: It has been shown that the ratio of systolic duration to diastolic duration (S/D) is a valuable global index of ventricular dysfunction in pediatric dilated and restrictive cardiomyopathy and is also a valuable index of the ventricular function of single systemic right ventricles in children who have undergone palliation of hypoplastic left-heart syndrome. The purposes of this study were to establish normal values for the S/D ratio in children without heart disease and to investigate its variation with heart rate (HR), age, and body surface area., Methods: Of 752 children found to have functional murmurs by clinical means, 179 (24% of the total database) had trace holosystolic tricuspid regurgitation. These patients ranged in age from 0.02 months to 19 years. For this study, the diastolic interval was defined as the period of right ventricular filling (ie, the period between 2 tricuspid regurgitant jets) and the systolic interval as the remainder of the cardiac cycle corresponding to the duration of holosystolic tricuspid regurgitation, including the periods of isovolumic contraction and relaxation. The relations between the systolic and diastolic periods and their ratio (S/D ratio) and HR, age, and body surface area were evaluated using univariate and multivariate linear regression analysis., Results: Patient's age ranged from 0.02 months to 19 years (mean, 70.18+/-65.12 months), body surface area from 0.11 to 2.51 m2 (mean, 0.85+/-0.55 m2), and HR from 50 to 156 beats/min (mean, 96.72+/-23.19 beats/min). The systolic period ranged from 208.5 to 467 ms (mean, 314.08+/-52.57 ms) and the diastolic period from 166.5 to 809 ms (mean, 341.34+/-129.61 ms), yielding a S/D ratio ranging from 0.397 to 1.62 (mean, 0.995+/-0.23). Systolic period duration showed a linear negative decrease with increasing HR (y=1.9228x+500.05, r=-0.85). Diastolic duration decreased in an exponential fashion as HR increased (y=130,679x(-1.3232), r=-0.88). The S/D ratio correlated positively with HR (y=-1.656+0.0265 HR-0.000954 HR2, r=76). On multivariate analysis, no significant correlations of S/D ratio with age or body surface area were found., Conclusions: The results of this study provide useful reference values for the S/D ratio across a wide range of HRs in children, adolescents, and young adults.