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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. [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: 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: Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Methods: Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. Results: All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p < 0.001) and controls (from 1194 ± 26 ms to 1273 ± 44 ms, p < 0. 001). T2DM patients showed blunted relative stress non-contrast T1 response (T2DM: ΔT1 = 4.1 ± 2.9% vs. controls: ΔT1 = 6.6 ± 2.6%, p = 0.007) due to a blunted maximal T1 during adenosine stress (T2DM 1244 ± 44 ms vs. controls 1273 ± 44 ms, p = 0.045). Conclusions: Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention. [ABSTRACT FROM AUTHOR]

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 pixelerosions. 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. [ABSTRACT FROM AUTHOR]

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 T1spleen 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 (ΔSIspleen) and the "splenic switch-off" sign on conventional stress/rest gadolinium perfusion imaging. T1spleen values were obtained blinded to perfusion ΔSIspleen, 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). T1spleen decreased significantly during adenosine stress (mean ΔSIspleen ~ -40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔSIspleen correlated strongly with ΔSIspleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔSIspleen 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. ΔSIspleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR. [ABSTRACT FROM AUTHOR]

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 ( = 13 atrial fibrillation, = 2 sinus tachycardia; mean HR range 93-121 bpm). n n 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 ( = 0.04), with slightly shorter T1 values in systole p 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 R² = 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. [ABSTRACT FROM AUTHOR]

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. [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]

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 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]