Cardiovascular magnetic resonance normal values in children for biventricular wall thickness and mass.

BACKGROUND: Pediatric patients are becoming increasingly referred for cardiovascular magnetic resonance (CMR). Measurement of ventricular wall thickness is typically part of the assessment and can be of diagnostic importance, e.g. in arterial hypertension. However, normal values for left ventricular (LV) and right ventricular (RV) wall thickness in pediatric patients are lacking. The aim of this study was to establish pediatric centile charts for segmental LV and RV myocardial thickness in a retrospective multicenter CMR study. METHODS: CMR was performed in 161 healthy children and adolescents with an age range between 6 and 18 years from two centers in the UK and Germany as well as from a previously published CMR project of the German Competence Network for Congenital Heart Defects. LV myocardial thickness of 16 segments was measured on the short axis stack using the American Heart Association segmentation model. In addition, the thickness of the RV inferior and anterior free wall as well as biventricular mass was measured. RESULTS: The mean age (standard deviation) of the subjects was 13.6 (2.9) years, 64 (39.7%) were female. Myocardial thickness of the basal septum (basal antero- and inferoseptal wall) was 5.2 (1.1) mm, and the basal lateral wall (basal antero- and inferolateral) measured 5.1 (1.2) mm. Mid-ventricular septum (antero- and inferoseptal wall) measured 5.5 (1.2) mm, and mid-ventricular lateral wall (antero- and inferolateral wall) was 4.7 (1.2) mm. Separate centile charts for boys and girls for all myocardial segments and myocardial mass were created because gender was significantly correlated with LV myocardial thickness (p < 0.001 at basal level, p = 0.001 at midventricular level and p = 0.005 at the apex) and biventricular mass (LV, p < 0.001; RV, p < 0.001). CONCLUSION: We established CMR normal values of segmental myocardial thickness and biventricular mass in children and adolescents. Our data are of use for the detection of abnormal myocardial properties and can serve as a reference in future studies and clinical practice.

Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial.

BACKGROUND: Patients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown. METHODS: We did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02859311. FINDINGS: Between April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5-67·2]; p=0·0001). After 6 months, 25 (96%) of 26 patients assigned initially to continue treatment attempted its withdrawal. During the following 6 months, nine patients met the primary endpoint of relapse (Kaplan-Meier estimate of event rate 36·0% [95% CI 20·6-57·8]). No deaths were reported in either group and three serious adverse events were reported in the treatment withdrawal group: hospital admissions for non-cardiac chest pain, sepsis, and an elective procedure. INTERPRETATION: Many patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal. Until robust predictors of relapse are defined, treatment should continue indefinitely. FUNDING: British Heart Foundation, Alexander Jansons Foundation, Royal Brompton Hospital and Imperial College London, Imperial College Biomedical Research Centre, Wellcome Trust, and Rosetrees Trust.

Validation of T2* in-line analysis for tissue iron quantification at 1.5 T.

BACKGROUND: There is a need for improved worldwide access to tissue iron quantification using T2* cardiovascular magnetic resonance (CMR). One route to facilitate this would be simple in-line T2* analysis widely available on MR scanners. We therefore compared our clinically validated and established T2* method at Royal Brompton Hospital (RBH T2*) against a novel work-in-progress (WIP) sequence with in-line T2* measurement from Siemens (WIP T2*). METHODS: Healthy volunteers (n = 22) and patients with iron overload (n = 78) were recruited (53 males, median age 34 years). A 1.5 T study (Magnetom Avanto, Siemens) was performed on all subjects. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used to acquire both RBH T2* images and WIP T2* maps for each participant. Cardiac white blood (WB) and black blood (BB) sequences were acquired. Intraobserver, interobserver and interstudy reproducibility were measured on the same data from a subset of 20 participants. RESULTS: Liver T2* values ranged from 0.8 to 35.7 ms (median 5.1 ms) and cardiac T2* values from 6.0 to 52.3 ms (median 31 ms). The coefficient of variance (CoV) values for direct comparison of T2* values by RBH and WIP were 6.1-7.8 % across techniques. Accurate delineation of the septum was difficult on some WIP T2* maps due to artefacts. The inability to manually correct for noise by truncation of erroneous later echo times led to some overestimation of T2* using WIP T2* compared with the RBH T2*. Reproducibility CoV results for RBH T2* ranged from 1.5 to 5.7 % which were better than the reproducibility of WIP T2* values of 4.1-16.6 %. CONCLUSIONS: Iron estimation using the T2* CMR sequence in combination with Siemens' in-line data processing is generally satisfactory and may help facilitate global access to tissue iron assessment. The current automated T2* map technique is less good for tissue iron assessment with noisy data at low T2* values.

Comparison of 3 T and 1.5 T for T2* magnetic resonance of tissue iron.

BACKGROUND: T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T. METHODS: A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*. RESULTS: Association between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (R (2) = 0.954, p < 0.001 for heart white-blood (WB) imaging; R (2) = 0.931, p < 0.001 for heart black-blood (BB) imaging; R (2) = 0.993, p < 0.001 for liver imaging). R2* approximately doubled between 1.5 T and 3 T with linear fits for both heart and liver (94, 94 and 105 % respectively). Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3 T (3.5 to 6.5 %) than at 1.5 T (1.4 to 5.7 %) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3 T BB sequence (median 4, IQR 2-5) compared with the 1.5 T BB sequence (4 [3-5], p = 0.007). CONCLUSION: Heart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*.

T1 at 1.5T and 3T compared with conventional T2* at 1.5T for cardiac siderosis.

BACKGROUND: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers. METHODS: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T. RESULTS: In healthy volunteers, median T1 was 1014 ms (full range 939-1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056-1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values <20 ms) had T1 values <939 ms at 1.5T, and <1056 ms at 3T. Associations between T2* and T1 were found to be moderate with y =377 · x(0.282) at 1.5T (R(2) = 0.717), and y =406 · x(0.294) at 3T (R(2) = 0.715). Measures of reproducibility of T1 appeared superior to T2*. CONCLUSIONS: T1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration.

Two-center validation of Pilot Tone based cardiac triggering of a comprehensive cardiovascular magnetic resonance examination.

The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. To evaluate the performance of PTC triggering in a comprehensive CMR exam. Fifteen volunteers and 20 patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

Two-center validation of Pilot Tone Based Cardiac Triggering of a Comprehensive Cardiovascular Magnetic Resonance Examination.

Background: The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. Purpose: To evaluate the performance of PTC triggering in a comprehensive CMR exam. Methods: Fifteen volunteers and twenty patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Results: Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. Conclusion: PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

Myocardial deformation assessed by CMR in children after multisystem inflammatory syndrome (MIS-C).

BACKGROUND: Short-term sequelae of Multisystem Inflammatory Syndrome in Children (MIS-C), recently published by our institution, showed rapid improvement of the cardiac abnormalities within a few weeks after the onset of the disease. However, subtle residual abnormalities, affecting mainly the myocardial interstitium, were shown in some of the patients. The current study aimed to assess myocardial deformation with CMR shortly after MIS-C. METHODS: Sixty children were included into the study; 30 following MIS-C (onset-to-scan mean 27 days, SD 11) and 30 controls. Strain values were compared between patients and controls and additionally to published paediatric normal CMR values. U-Mann Whitney test was used for comparison of the myocardial deformation between patients and controls. RESULTS: Median age of the patients was 9.0 years (range 0.99-14.4) and controls 9.8 years (range 4.7-14.9). All conventional CMR parameters in patients were in normal range. Strain values were significantly lower in patients than in controls. When compared to published centile graphs, radial and circumferential global strain was within 2.5th and 97.5th centile in all patients. Eleven patients had global longitudinal strain between 2.5th centile and 50th centile, 1 patient was below 2.5th centile and all the others above 50th centile. Only 3 controls had global longitudinal strain between 2.5th centile and 50th centile, all other had higher strain. CONCLUSIONS: This study demonstrates that myocardial deformation indices measured by CMR are within normal range in the vast majority of the patients within a few weeks after the onset of MIS-C. However, when compared to healthy controls, all strain parameters were lower in patients.

Initial investigation of free-breathing 3D whole-heart stress myocardial perfusion MRI.

Objective: Myocardial first-pass perfusion imaging with MRI is well-established clinically. However, it is potentially weakened by limited myocardial coverage compared to nuclear medicine. Clinical evaluations of whole-heart MRI perfusion by 3D methods, while promising, have to date had the limit of breathhold requirements at stress. This work aims to develop a new free-breathing 3D myocardial perfusion method, and to test its performance in a small patient population. Methods: This work required tolerance to respiratory motion for stress investigations, and therefore employed a "stack-of-stars" hybrid Cartesian-radial MRI acquisition method. The MRI sequence was highly optimised for rapid acquisition and combined with a compressed sensing reconstruction. Stress and rest datasets were acquired in four healthy volunteers, and in six patients with coronary artery disease (CAD), which were compared against clinical reference information. Results: This free-breathing method produced datasets that appeared consistent with clinical reference data in detecting moderate-to-strong induced perfusion abnormalities. However, the majority of the mild defects identified clinically were not detected by the method, potentially due to the presence of transient myocardial artefacts present in the images. Discussion: The feasibility of detecting CAD using this 3D first-pass perfusion sequence during free-breathing is demonstrated. Good agreement on typical moderate-to-strong CAD cases is promising, however, questions still remain on the sensitivity of the technique to milder cases.

Cardiovascular magnetic resonance of acute myocardial infarction following traumatic coronary artery dissection.

Traumatic coronary artery dissection is a very rare cause of myocardial infarction. Occurrence of this condition late in the posttraumatic period is extremely uncommon. We present a case of a young patient with acute myocardial infarction 4 weeks after blunt chest trauma. Coronary angiography showed left anterior descending artery dissection as well as thrombus formation, and multiple small infarctions were shown by cardiovascular magnetic resonance.

Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis.

OBJECTIVES: The goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis. BACKGROUND: Myocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions. METHODS: Between January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service. RESULTS: A total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis. CONCLUSIONS: Midwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification.