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Aims: Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa)., Methods and Results: One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate., Conclusion: Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice., Competing Interests: Conflict of interest: S.K.P. has patent authorship rights for US patent US20120078084A1: ‘System and methods for shortened Look-Locker inversion recovery (Sh-MOLLI) cardiac gated mapping of T1’, granted on 15 March 2016. S.K.P., I.A.P., and V.M.F. have authorship rights for patent pending PCT/GB2020/051189: ‘A method for identity validation and quality assurance of quantitative magnetic resonance imaging protocols’, filed on 15 May 2020. IPs are owned and managed by Oxford University Innovations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection., (© 2023. The Author(s).)

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans., Methods: A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC., Results: A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P <0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions ( r =0.77-0.79; ICC=0.77-0.87; P <0.001) and intermediate-intensity lesions ( r =0.70-0.76; ICC=0.82-0.85; P <0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second., Conclusions: VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

Recent developments in artificial intelligence have generated increasing interest to deploy automated image analysis for diagnostic imaging and large-scale clinical applications. However, inaccuracy from automated methods could lead to incorrect conclusions, diagnoses or even harm to patients. Manual inspection for potential inaccuracies is labor-intensive and time-consuming, hampering progress towards fast and accurate clinical reporting in high volumes. To promote reliable fully-automated image analysis, we propose a quality control-driven (QCD) segmentation framework. It is an ensemble of neural networks that integrate image analysis and quality control. The novelty of this framework is the selection of the most optimal segmentation based on predicted segmentation accuracy, on-the-fly. Additionally, this framework visualizes segmentation agreement to provide traceability of the quality control process. In this work, we demonstrated the utility of the framework in cardiovascular magnetic resonance T1-mapping - a quantitative technique for myocardial tissue characterization. The framework achieved near-perfect agreement with expert image analysts in estimating myocardial T1 value (r=0.987,p<.0005; mean absolute error (MAE)=11.3ms), with accurate segmentation quality prediction (Dice coefficient prediction MAE=0.0339) and classification (accuracy=0.99), and a fast average processing time of 0.39 second/image. In summary, the QCD framework can generate high-throughput automated image analysis with speed and accuracy that is highly desirable for large-scale clinical applications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors declare that a patent is filed for the methods used in this submitted work., (Copyright © 2021. Published by Elsevier B.V.)

Stress and rest T1-mapping may assess for myocardial ischemia and extracellular volume (ECV). However, the stress T1 response is method-dependent, and underestimation may lead to misdiagnosis. Further, ECV quantification may be affected by time, as well as the number and dosage of gadolinium (Gd) contrast administered. We compared two commonly available T1-mapping approaches in their stress T1 response and ECV measurement stability. Healthy subjects (n = 10, 50% female, 35 ± 8 years) underwent regadenoson stress CMR (1.5 T) on two separate days. Prototype ShMOLLI 5(1)1(1)1 sequence was used to acquire consecutive mid-ventricular T1-maps at rest, stress and post-Gd contrast to track the T1 time evolution. For comparison, standard MOLLI sequences were used: MOLLI 5(3)3 Low (256 matrix) & High (192 matrix) Heart Rate (HR) to acquire rest and stress T1-maps, and MOLLI 4(1)3(1)2 Low & High HR for post-contrast T1-maps. Stress and rest myocardial blood flow (MBF) maps were acquired after IV Gd contrast (0.05 mmol/kg each). Stress T1 reactivity (delta T1) was defined as the relative percentage increase in native T1 between rest and stress. Myocardial T1 values for delta T1 (dT1) and ECV were calculated. Residuals from the identified time dependencies were used to assess intra-method variability. ShMOLLI achieved a greater stress T1 response compared to MOLLI Low and High HR (peak dT1 = 6.4 ± 1.7% vs. 4.8 ± 1.3% vs. 3.8 ± 1.0%, respectively; both p < 0.0001). ShMOLLI dT1 correlated strongly with stress MBF (r = 0.77, p < 0.001), compared to MOLLI Low HR (r = 0.65, p < 0.01) and MOLLI High HR (r = 0.43, p = 0.07). ShMOLLI ECV was more stable to gadolinium dose with less time drift (0.006-0.04% per minute) than MOLLI variants. Overall, ShMOLLI demonstrated less intra-individual variability than MOLLI variants for stress T1 and ECV quantification. Power calculations indicate up to a fourfold (stress T1) and 7.5-fold (ECV) advantage in sample-size reduction using ShMOLLI. Our results indicate that ShMOLLI correlates strongly with increased MBF during regadenoson stress and achieves a significantly higher stress T1 response, greater effect size, and greater ECV measurement stability compared with the MOLLI variants tested.

Background: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials., Purpose: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use., Methods: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites., Results: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R 2  > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions., Conclusions: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Competing Interests: Declaration of Competing Interest SKP has patent authorship rights for U.S. patent US20120078084A1. Systems and methods for shortened Look Locker inversion recovery (Sh-MOLLI) cardiac gated mapping of T1. Granted March 15, 2016. IP is managed by Oxford University Innovations; the license exclusively transferred to Siemens Healthcare. QZ, SKP, KW, IAP, VMF have authorship rights for pending patent PCT/GB2020/051189. A method for identity validation and quality assurance of quantitative magnetic resonance imaging protocols. Filed May 15, 2020. IP is owned and managed by Oxford University Innovations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular magnetic resonance T1-mapping is increasingly used for tissue characterization, commonly based on Modified Look-Locker Inversion recovery (MOLLI). However, there are numerous MOLLI variants with differing normal ranges. This lack of standardization presents confusion and difficulty in inter-center comparisons, hindering widespread adoption of T1-mapping., Methods: To address this, we performed a structured literature search for native left ventricular myocardial T1-mapping in healthy humans measured using MOLLI variants at 1.5 and 3 Tesla, across scanner vendors. We then used k-means clustering to structure normal MOLLI-T1 values according to magnetic field strength, and investigated correlations between common imaging parameters: repetition time (TR), echo time (TE), flip angle (FA)., Results: We analyzed data from 2207 healthy controls in 76 independent reports. Normal MOLLI-T1 standard deviations varied by 11-fold, and dependencies on TE, TR, and FA differed between 1.5 T and 3 T, thwarting meaningful T1 standardization even within a single field strength, including the use of Z-score. However, divergent MOLLI-T1 norms may be structured using data clustering. For 1.5 T, two clusters emerged: Cluster1 1.5T : T1 = 958 ± 16 ms (n = 1280); Cluster2 1.5T : T1 = 1027 ± 19 ms (n = 386). For 3 T, three clusters emerged: Cluster1 3T : T1 = 1160 ± 21 ms (n = 330); Cluster2 3T : T1 = 1067 ± 18 ms (n = 178); Cluster3 3T : T1 = 1227 ± 19 ms (n = 41). We then propose the concept of an online calculator for assigning local norms to a known MOLLI-T1 cluster, allowing benchmarking against published norms., Conclusion: Clustered structuring allows T1 standardization of widely-divergent MOLLI variants, benchmarking local norms (usually based on smaller samples) against published norms (larger samples). This may increase confidence and quality control in method implementation, facilitating wider clinical adoption of T1-mapping., Competing Interests: Declaration of Competing Interest SKP has patent authorship rights for U.S. patent US20120078084A1. Systems and methods for shortened Look Locker inversion recovery (Sh-MOLLI) cardiac gated mapping of T1. Granted March 15, 2016. IP is managed by Oxford University Innovations; the license exclusively transferred to Siemens Healthcare. All other authors have no industry relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement.This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted.

This JACC Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation (Lake Louise Criteria) that include options to use parametric mapping techniques. While each parameter may indicate myocardial inflammation, the authors propose that CMR provides strong evidence for myocardial inflammation, with increasing specificity, if the CMR scan demonstrates the combination of myocardial edema with other CMR markers of inflammatory myocardial injury. This is based on at least one T2-based criterion (global or regional increase of myocardial T2 relaxation time or an increased signal intensity in T2-weighted CMR images), with at least one T1-based criterion (increased myocardial T1, extracellular volume, or late gadolinium enhancement). While having both a positive T2-based marker and a T1-based marker will increase specificity for diagnosing acute myocardial inflammation, having only one (i.e., T2-based OR T1-based) marker may still support a diagnosis of acute myocardial inflammation in an appropriate clinical scenario, albeit with less specificity. The update is expected to improve the diagnostic accuracy of CMR further in detecting myocardial inflammation., (Copyright © 2018. Published by Elsevier Inc.)

In vivo mapping of the myocardial T1 relaxation time has recently attained wide clinical validation of its potential utility. In this review, we address the basic principles of the T1 mapping techniques, with particular attention to the emerging application of vasodilatory stress agents to interrogate the myocardial microvascular compartment, and differences between commonly used T1 mapping methods when applied in clinical practice.

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Background: Native T1-mapping provides quantitative myocardial tissue characterization for cardiovascular diseases (CVD), without the need for gadolinium. However, its translation into clinical practice is hindered by differences between techniques and the lack of established reference values. We provide typical myocardial T1-ranges for 18 commonly encountered CVDs using a single T1-mapping technique - Shortened Look-Locker Inversion Recovery (ShMOLLI), also used in the large UK Biobank and Hypertrophic Cardiomyopathy Registry study., Methods: We analyzed 1291 subjects who underwent CMR (1.5-Tesla, MAGNETOM-Avanto, Siemens Healthcare, Erlangen, Germany) between 2009 and 2016, who had a single CVD diagnosis, with mid-ventricular T1-map assessment. A region of interest (ROI) was placed on native T1-maps in the "most-affected myocardium", characterized by the presence of late gadolinium enhancement (LGE), or regional wall motion abnormalities (RWMA) on cines. Another ROI was placed in the "reference myocardium" as far as possible from LGE/RWMA, and in the septum if no focal abnormality was present. To further define normality, we included native T1 of healthy subjects from an existing dataset after sub-endocardial pixel-erosions., Results: Native T1 of patients with normal CMR (938 ± 21 ms) was similar compared to healthy subjects (941 ± 23 ms). Across all patient groups (57 ± 19 yrs., 65% males), focally affected myocardium had significantly different T1 value compared to reference myocardium (all p < 0.001). In the affected myocardium, cardiac amyloidosis (1119 ± 61 ms) had the highest native T1 compared to normal and all other CVDs, while iron-overload (795 ± 58 ms) and Anderson-Fabry disease (863 ± 23 ms) had the lowest native reference T1 (all p < 0.001). Future studies designed to detect the large T1 differences between affected and reference myocardium are estimated to require small sample-sizes (n < 50). However, studies designed to detect the small T1 differences between reference myocardium in CVDs and healthy controls can require several thousand of subjects., Conclusions: We provide typical T1-ranges for common clinical cardiac conditions in the largest cohort to-date, using ShMOLLI T1-mapping at 1.5 T. Sample-size calculations from this study may be useful for the design of future studies and trials that use T1-mapping as an endpoint.

Background: With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR., Methods: The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR). The GCMR team has developed a web-based data infrastructure, data use policy and participation agreement, data-harmonizing methods, and site-training tools based on results from an international survey of CMR programs., Results: At present, 17 CMR programs have established a legal agreement to participate in GCMR, amongst them 10 have contributed CMR data, totaling 62,456 studies. There is currently a predominance of CMR centers with more than 10 years of experience (65%), and the majority are located in the United States (63%). The most common clinical indications for CMR have included assessment of cardiomyopathy (21%), myocardial viability (16%), stress CMR perfusion for chest pain syndromes (16%), and evaluation of etiology of arrhythmias or planning of electrophysiological studies (15%) with assessment of cardiomyopathy representing the most rapidly growing indication in the past decade. Most CMR studies involved the use of gadolinium-based contrast media (95%)., Conclusions: We present the goals, mission and vision, infrastructure, preliminary results, and challenges of the GCMR., Trial Registration: Identification number on ClinicalTrials.gov: NCT02806193 . Registered 17 June 2016.

Background: Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the "splenic switch-off" sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium., Methods: Two-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1 spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 μg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSI spleen ) and the "splenic switch-off" sign on conventional stress/rest gadolinium perfusion imaging. T1 spleen values were obtained blinded to perfusion ΔSI spleen , both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects., Results: Normal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p = 0.01, respectively). T1 spleen decreased significantly during adenosine stress (mean ΔT1 spleen  ~ -40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔT1 spleen correlated strongly with ΔSI spleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔT1 spleen threshold of ≥ -30 ms during stress predicted the "splenic switch-off" sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%)., Conclusions: Adenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual "splenic switch-off" sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔT1 spleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR.

Background: T1-mapping using the Shortened Modified Look-Locker Inversion Recovery (ShMOLLI) technique enables non-invasive assessment of important myocardial tissue characteristics. However, tachyarrhythmia may cause mistriggering and inaccurate T1 estimation. We set out to test whether systolic T1-mapping might overcome this, and whether T1 values or data quality would be significantly different compared to conventional diastolic T1-mapping., Methods: Native T1 maps were acquired using ShMOLLI at 1.5 T (Magnetom Avanto, Siemens Healthcare) in 10 healthy volunteers (5 male) in sinus rhythm, at varying prescribed trigger delay (TD) times: 0, 50, 100 and 150 ms (all "systolic"), 340 ms (MOLLI TD 500 ms, the conventional TD for ShMOLLI) and also "end diastolic". T1 maps were also acquired using a shorter readout, to explore the effect of reducing image readout time and sensitivity to systolic motion. The feasibility and image quality of systolic T1-mapping was tested in 15 patients with tachyarrhythmia (n = 13 atrial fibrillation, n = 2 sinus tachycardia; mean HR range 93-121 bpm)., Results: In healthy volunteers, systolic readout increased the thickness of myocardium compared to the diastolic readout. There was a small overall effect of TD on T1 values (p = 0.04), with slightly shorter T1 values in systole compared to diastole (maximum difference 10 ms). While there were apparent gender differences (with no effect of TD on T1 values in males, more marked differences in females, and exaggeration of this effect in thinner myocardial segments in females), dilatation and erosion of contours suggested that the effect of TD on T1 in females was almost entirely due to more partial-volume effects in diastole. All T1 maps were of excellent quality, but systolic TD and shorter readout were associated with less variability in segmental T1 values. In tachycardic patients, systolic acquisitions produced consistently excellent T1 maps (median R (2) = 0.993)., Conclusions: In healthy volunteers, systolic ShMOLLI T1-mapping reduces T1 variability and reports clinically equivalent T1 values to conventional diastolic readout; slightly shorter T1 values in systole are mostly explained by reduced partial-volume effects due to the increase in functional myocardial thickness. In patients with tachyarrhythmia, systolic ShMOLLI T1-mapping is feasible, circumvents mistriggering and produces excellent quality T1 maps. This extends its clinical applicability to challenging rhythms (such as rapid atrial fibrillation) and aids the investigation of thinner myocardial segments. With further validation, systolic T1-mapping may become a new and convenient standard for myocardial T1-mapping.

Background: Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds., Methods: We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE., Results: Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis., Conclusion: Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In addition, T1-mapping offers significant incremental diagnostic value, detecting additional areas of myocardial involvement beyond T2W and LGE imaging and identified extra cases when these conventional methods failed to identify abnormalities. In the future, it may be possible to perform gadolinium-free CMR using cine and T1-mapping for tissue characterization and may be particularly useful for patients in whom gadolinium contrast is contraindicated.

Cardiac magnetic resonance (CMR) imaging is a well-established noninvasive imaging modality in clinical cardiology. Its unsurpassed accuracy in defining cardiac morphology and function and its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. Late gadolinium enhancement was a major advancement in the development of tissue characterization techniques, allowing the unique ability of CMR to differentiate ischemic heart disease from nonischemic cardiomyopathies. Using T2-weighted techniques, areas of edema and inflammation can be identified in the myocardium. A new generation of myocardial mapping techniques are emerging, enabling direct quantitative assessment of myocardial tissue properties in absolute terms. This review will summarize recent developments involving T1-mapping and T2-mapping techniques and focus on the clinical applications and future potential of these evolving CMR methodologies.

Background: Aortic stenosis (AS) leads to diffuse fibrosis in the myocardium, which is linked to adverse outcome. Myocardial T1 values change with tissue composition., Objective: To test the hypothesis that our recently developed non-contrast cardiac magnetic resonance (CMR) T1 mapping sequence could identify myocardial fibrosis without contrast agent., Design, Setting and Patients: A prospective CMR non-contrast T1 mapping study of 109 patients with moderate and severe AS and 33 age- and gender-matched controls., Methods: CMR at 1.5 T, including non-contrast T1 mapping using a shortened modified Look-Locker inversion recovery sequence, was carried out. Biopsy samples for histological assessment of collagen volume fraction (CVF%) were obtained in 19 patients undergoing aortic valve replacement., Results: There was a significant correlation between T1 values and CVF% (r=0.65, p=0.002). Mean T1 values were significantly longer in all groups with severe AS (972 ± 33 ms in severe asymptomatic, 1014 ± 38 ms in severe symptomatic) than in normal controls (944 ± 16 ms) (p<0.05). The strongest associations with T1 values were for aortic valve area (r=-0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008), and these were the only independent predictors on multivariate analysis., Conclusions: Non-contrast T1 values are increased in patients with severe AS and further increase in symptomatic compared with asymptomatic patients. T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future.

Background: T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients., Materials and Methods: The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms

Aims Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa). Methods and results One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate. Conclusion Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: The use of cardiovascular magnetic resonance (CMR) for diagnosis and management of a broad range of cardiac and vascular conditions has quickly expanded worldwide. It is essential to understand how CMR is utilized in different regions around the world and the potential practice differences between high-volume and low-volume centers. Methods: CMR practitioners and developers from around the world were electronically surveyed by the Society for Cardiovascular Magnetic Resonance (SCMR) twice, requesting data from 2017. Both surveys were carefully merged, and the data were curated professionally by a data expert using cross-references in key questions and the specific media access control IP address. According to the United Nations classification, responses were analyzed by region and country and interpreted in the context of practice volumes and demography. Results: From 70 countries and regions, 1092 individual responses were included. CMR was performed more often in academic (695/1014, 69%) and hospital settings (522/606, 86%), with adult cardiologists being the primary referring providers (680/818, 83%). Evaluation of cardiomyopathy was the top indication in high-volume and low-volume centers (p = 0.06). High-volume centers were significantly more likely to list evaluation of ischemic heart disease (e.g., stress CMR) as a primary indicator compared to low-volume centers (p < 0.001), while viability assessment was more commonly listed as a primary referral reason in low-volume centers (p = 0.001). Both developed and developing countries noted cost and competing technologies as top barriers to CMR growth. Access to scanners was listed as the most common barrier in developed countries (30% of responders), while lack of training (22% of responders) was the most common barrier in developing countries. Conclusion: This is the most extensive global assessment of CMR practice to date and provides insights from different regions worldwide. We identified CMR as heavily hospital-based, with referral volumes driven primarily by adult cardiology. Indications for CMR utilization varied by center volume. Efforts to improve the adoption and utilization of CMR should include growth beyond the traditional academic, hospital-based location and an emphasis on cardiomyopathy and viability assessment in community centers. [ABSTRACT FROM AUTHOR]

Aims  Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR). Methods and results  We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.0 (1.5–3.5)]; 35 individuals with no history of AF but similar stroke risk to Group 1 [Group 2; median CHA2DS2-VASc = 3.0 (2.0–4.0)]; and 23 low-risk individuals in SR [Group 3; median CHA2DS2-VASc = 0.0 (0.0–0.0)]. Cardiac function and LA flow characteristics were evaluated using cardiac magnetic resonance. Before cardioversion, Group 1 displayed impaired left ventricular (LV) and LA function, reduced LA flow velocities and vorticity, and a higher normalized vortex volume (all P  < 0.001 vs. Groups 2 and 3). After restoration of SR at ≥4-week post-cardioversion, LV systolic function and LA flow parameters improved significantly (all P  < 0.001 vs. pre-cardioversion) and were no longer different from those in Group 2. However, in the presence of SR, LA flow peak and mean velocity, and vorticity were lower in Groups 1 and 2 vs. Group 3 (all P  < 0.01), and were associated with impaired LA emptying fraction (LAEF) and LV diastolic dysfunction. Conclusion  Patients at moderate-to-high stroke risk display altered LA flow characteristics in SR in association with an LA myopathic phenotype and LV diastolic dysfunction, regardless of a history of AF. [ABSTRACT FROM AUTHOR]

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear. Methods: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity. Discussion: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity. Clinical Trial registration: ISRCTN 58667920. Registered 04 August 2020. [ABSTRACT FROM AUTHOR]

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR). Methods: Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0–6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27–35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan–rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared. Results: Same-day scan–rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan–rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05). Conclusions: LA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm. [ABSTRACT FROM AUTHOR]

Background: Many children presenting with myocarditis may not fully recover and have long-term complications, including dilated cardiomyopathy. Magnetic resonance imaging (MRI) has a potential for early detection of persistent changes with long-term implications, but is not performed routinely in the monitoring of myocarditis.Purpose: To monitor adolescents who present with acute myocarditis using MRI and routine diagnostic tests over the short- to mid-term.Study Type: Prospective.Population: Eighteen consecutive adolescents (median age 15.5, interquartile range 14.8-16.9 years, 78% male) with acute myocarditis.Field Strength: A 3T scanner including cine steady-state free precession (SSFP), dark-blood T2 -weighted (T2 W) images, and late gadolinium enhancement (LGE).Assessment: The diagnosis of acute myocarditis was based on clinical symptoms and signs and MRI criteria (cine, T2 -W images, LGE). Follow-up MRI was performed after median 7 months (range 6-9 months). Other routine diagnostic tests included electrocardiogram (ECG), high-sensitivity troponin levels, transthoracic echocardiography, and Holter monitoring.Statistical Tests: Fisher's exact test, Wilcoxon test for paired samples, Mann-Whitney test for independent samples, Kruskal-Wallis test.Results: At baseline, 17 patients (94%) had elevated troponin levels and/or ST-T changes on resting ECG; ECG showed depressed left ventricular ejection fraction (LVEF<50%) in four patients (22%). At follow-up there was a complete recovery in 16 patients (89%) observed with routinely performed tests, with two cases of persistent ventricular arrhythmia. Despite normal left ventricular volume and LVEF, MRI disclosed ongoing active inflammation in five patients (28%), healed myocarditis with persistent scars in eight patients (44%), and complete resolution of initially observed changes in five patients (28%).Data Conclusion: In children with acute myocarditis, despite normalization of other routinely assessed parameters (including LVEF), there is a high prevalence of persistent MRI changes showing ongoing disease or remnant scars at follow-up. MRI may allow early detection and prevention of long-term complications of myocarditis in the follow-up care of children with acute myocarditis.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020. J. Magn. Reson. Imaging 2020;52:488-496. [ABSTRACT FROM AUTHOR]

Background: Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). Methods: STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. Results: Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P < 0.001), higher incidence and larger extent of MVO (85% vs. 40%, P = 0.016) & [4.0 (0.5–9.5)% vs. 0 (0–3.0)%, P = 0.025]. The average T1 value was an independent predictor of acute LGE (β 0.61, 95%CI 0.13 to 1.09; P = 0.015), extent of MVO (β 0.22, 95%CI 0.03 to 0.41, P = 0.028) and final infarct size (β 0.63, 95%CI 0.21 to 1.05; P = 0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE > 9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). Conclusion: Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics. [ABSTRACT FROM AUTHOR]

Myocardial inflammation occurs following activation of the cardiac immune system, producing characteristic changes in the myocardial tissue. Cardiovascular magnetic resonance is the non-invasive imaging gold standard for myocardial tissue characterization, and is able to detect image signal changes that may occur resulting from inflammation, including edema, hyperemia, capillary leak, necrosis, and fibrosis. Conventional cardiovascular magnetic resonance for the detection of myocardial inflammation and its sequela include T2-weighted imaging, parametric T1- and T2-mapping, and gadolinium-based contrast-enhanced imaging. Emerging techniques seek to image several parameters simultaneously for myocardial tissue characterization, and to depict subtle immune-mediated changes, such as immune cell activity in the myocardium and cardiac cell metabolism. This review article outlines the underlying principles of current and emerging cardiovascular magnetic resonance methods for imaging myocardial inflammation. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized.Objectives: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR).Methods: A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]).Results: Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups.Conclusions: This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations. [ABSTRACT FROM AUTHOR]

Background: Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). Methods: 42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE). Results: AS patients had increased resting myocardial T1 (1196 ± 47 ms vs. 1168 ± 27 ms, p = 0.037), reduced MPRI (0.92 ± 0.31 vs. 1.74 ± 0.32, p < 0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240 ± 51 ms vs. 1238 ± 54 ms, p = 0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (AT1 3.7 ± 2.7% vs. 6.0 ± 4.2% in controls, p = 0.013). Seven months after AVR (n = 16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI. Conclusions: Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values. [ABSTRACT FROM AUTHOR]

Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic hypertrophic cardiomyopathy pre-LVH (genotype positive, LVH negative [G+LVH-]).A multicenter case-control study investigated crypts and 22 other cardiovascular magnetic resonance parameters in subclinical hypertrophic cardiomyopathy to determine their strength of association with sarcomere gene mutation carriage. The G+LVH- sample (n=73) was 29±13 years old and 51% were men. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5; 95% confidence interval [CI], 0.5-4.4; P=0.014 and for ≥2 crypts, β=3.0; 95% CI, 0.8-7.9; P=0.004). In combination with 3 other parameters: anterior mitral valve leaflet elongation (β=2.1; 95% CI, 1.7-3.1; P<0.001), abnormal LV apical trabeculae (β=1.6; 95% CI, 0.8-2.5; P<0.001), and smaller LV end-systolic volumes (β=1.4; 95% CI, 0.5-2.3; P=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95% CI, 0.8-0.9). In this G+LVH- population, cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared with the other combined mutations (47 versus 23%; odds ratio, 2.9; 95% CI, 1.1-7.9; P=0.045).The subclinical hypertrophic cardiomyopathy phenotype measured by cardiovascular magnetic resonance in a multicenter environment and consisting of crypts (particularly multiple), anterior mitral valve leaflet elongation, abnormal trabeculae, and smaller LV systolic cavity is indicative of the presence of sarcomere gene mutations and highlights the need for further study. [ABSTRACT FROM AUTHOR]

Background Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc. Methods 19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification. Results Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices. Conclusions Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc. [ABSTRACT FROM AUTHOR]

The article presents a study that characterizes myocardial tissue using noncontrast magnetic resonance T1 mapping. The study found a weak correlation between mean T1 and late gadolinium enhancement (LGE). It indicates that in hypertrophic (HCM) and dilated cardiomyopathy (DCM), noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in low-risk individuals.

Background: T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR. Methods: We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium. Results: All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p<0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p<0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p<0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %. Conclusions: Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis. [ABSTRACT FROM AUTHOR]

Background: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process.Methods: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer.Results: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004).Conclusions: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF. [ABSTRACT FROM AUTHOR]

Background: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems.Methods: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed.Results: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction.Conclusions: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.Objectives: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.Methods: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.Results: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).Conclusions: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality. [ABSTRACT FROM AUTHOR]

Background: Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities.Methods: Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated. Magnetic resonance imaging quantified LV ejection fraction (LVEF), peak systolic circumferential strain (PSCS), and left atrial volumes and function, whereas phosphorus-31 magnetic resonance spectroscopy evaluated ventricular energetics (ratio of phosphocreatine to ATP). AF burden was determined before and after ablation by 7-day Holter monitoring; intermittent ECG event monitoring was also undertaken after ablation to investigate for asymptomatic AF recurrence.Results: Before ablation, both LV function and energetics were significantly impaired in patients compared with control subjects (LVEF, 61% [interquartile range (IQR), 52%-65%] versus 71% [IQR, 69%-73%], P<0.001; PSCS, -15% [IQR, -11 to -18%] versus -18% [IQR, -17% to -19%], P=0.002; ratio of phosphocreatine to ATP, 1.81±0.35 versus 2.05±0.29, P=0.004). As expected, patients also had dilated and impaired left atria compared with control subjects (all P<0.001). Early after ablation (1-4 days), LVEF and PSCS improved in patients recovering SR from AF (LVEF, 7.0±10%, P=0.005; PSCS, -3.5±4.3%, P=0.001) but were unchanged in those in SR during both assessments (both P=NS). At 6 to 9 months after ablation, AF burden reduced significantly (from 54% [IQR, 1.5%-100%] to 0% [IQR 0%-0.1%]; P<0.001). However, LVEF and PSCS did not improve further (both P=NS) and remained impaired compared with control subjects (P<0.001 and P=0.003, respectively). Similarly, there was no significant improvement in atrial function from before ablation (P=NS), and this remained lower than in control subjects (P<0.001). The ratio of phosphocreatine to ATP was unaffected by heart rhythm during assessment and AF burden before ablation (both P=NS). It was unchanged after ablation (P=0.57), remaining lower than in control subjects regardless of both recovery of SR and freedom from recurrent AF (P=0.006 and P=0.002, respectively).Conclusions: Patients with lone AF have impaired myocardial energetics and subtle LV dysfunction, which do not normalize after ablation. These findings suggest that AF may be the consequence (rather than the cause) of an occult cardiomyopathy, which persists despite a significant reduction in AF burden after ablation. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Preterm birth relates to long-term alterations in cardiac morphology and function. Understanding whether preterm postnatal life is a tractable period of cardiovascular development that can be positively altered by nutrition is relevant to long-term outcomes. We hypothesized that being fed human breast milk during early postnatal life is beneficial to long-term cardiac structure and function in preterm-born individuals compared with infant formulas. METHODS: A total of 926 preterm-born infants originally took part in a randomized controlled trial of postnatal milk-feeding regimens between 1982 and 1985 across 5 different UK centers. Preterm-born individuals were randomly assigned to either breast milk donated by unrelated lactating women or nutrient-enriched formulas. We followed 102 individuals from this cohort: 30 of whom had been randomized to being fed exclusively human milk and 16 to being fed exclusively formula. As a comparison group, we recruited an additional 102 individuals born term to uncomplicated pregnancies. Cardiac morphology and function were assessed by MRI. RESULTS: Preterm-born individuals fed exclusively human milk as infants had increased left and right ventricular end-diastolic volume index (+9.73%, P = .04 and +18.2%, P < .001) and stroke volume index (+9.79%, P = .05 and +22.1%, P = .01) compared with preterm-born individuals who were exclusively formula fed as infants. CONCLUSIONS: This study provides the first evidence of a beneficial association between breast milk and cardiac morphology and function in adult life in those born preterm and supports promotion of human milk for the care of preterm infants to reduce long-term cardiovascular risk. [ABSTRACT FROM AUTHOR]