Detection Of Late Gadolinium Enhancement Research Articles

Description of the Two-Dimensional Layer-Specific Strain Echocardiography Phenotype of Arrhythmogenic Left Ventricular Cardiomyopathy

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is characterized by fibrofatty myocardial replacement demonstrated on cardiac magnetic resonance by late gadolinium enhancement (LGE) mainly involving the subepicardium. The aims of this study were to describe the layer-specific strain (LSS) echocardiography phenotype of ALVC and to compare it with LGE features. All consecutive ALVC pathogenic genetic variant carriers and noncarrier relatives were separated into four prespecified groups (overt ALVC [group 1], isolated LGE [group 2], pathogenic genetic variant carrier without ALVC phenotype [group 3], and no genetic variant carrier [group 4]) and studied accordingly using cardiac magnetic resonance and LSS echocardiography. Eighty-five individuals were included. Endocardial global longitudinal strain (GLS)-epicardial GLS (GLSepi) gradient was altered predominantly in group 1, illustrating transmural strain alteration in overt ALVC (3.8±1.1 in group 1, 4.3±2.2 in group 2, 5.2±1.2 in group 3, and 5.4±1.6 in group 4; P=.0017), whereas GLSepi was impaired predominantly in group 2 (endocardial GLS and GLSepi were 15.0±4.1% and 11.2±3.3%, respectively, in group 1; 20.5±2.8% and 16.2±5.5% in group 2; 23.4±3.3% and 18.2±2.7% in group 3; and 24.6±2.8% and 19.2±1.9% in group 4; P<.0001 for all). GLSepi was able to detect subepicardial LGE in genetic variant carriers without overt ALVC with an area under curve of 0.84 (95% CI, 0.73-0.95). However, segmental epicardial and endocardial strain behaved similarly and showed comparable diagnostic values for segmental LGE detection (areas under the curve, 0.72; [95% CI, 0.69-0.76] and 0.73 [95% CI, 0.70-0.76], respectively, P=.40). LSS alteration in ALVC progresses from the epicardium to the endocardium along with disease severity. Irrespective of LSS analysis, which did not provide incremental diagnostic value for the detection and localization of LGE, strain echocardiography was shown to be a potential surrogate marker of LGE, including in apparently healthy individuals with isolated LV fibrosis.

Evaluating a novel accelerated free-breathing late gadolinium enhancement imaging sequence for assessment of myocardial injury

IntroductionCardiac magnetic resonance imaging (MRI), including late gadolinium enhancement (LGE), plays an important role in the diagnosis and prognostication of ischemic and non-ischemic myocardial injury. Conventional LGE sequences require patients to perform multiple breath-holds and require long acquisition times. In this study, we compare image quality and assessment of myocardial LGE using an accelerated free-breathing sequence to the conventional standard-of-care sequence. MethodsIn this prospective cohort study, a total of 41 patients post Coronavirus 2019 (COVID-19) infection were included. Studies were performed on a 1.5 Tesla scanner with LGE imaging acquired using a conventional inversion recovery rapid gradient echo (conventional LGE) sequence followed by the novel accelerated free-breathing (FB-LGE) sequence. Image quality was visually scored (ordinal scale from 1 to 5) and compared between conventional and free-breathing sequences using the Wilcoxon rank sum test. Presence of per-segment LGE was identified according to the American Heart Association 16-segment myocardial model and compared across both conventional LGE and FB-LGE sequences using a two-sided chi-square test. The perpatient LGE extent was also evaluated using both sequences and compared using the Wilcoxon rank sum test. Interobserver variability in detection of per-segment LGE and per-patient LGE extent was evaluated using Cohen's kappa statistic and interclass correlation (ICC), respectively. ResultsThe mean acquisition time for the FB-LGE sequence was 17 s compared to 413 s for the conventional LGE sequence (P < 0.001). Assessment of image quality was similar between both sequences (P = 0.19). There were no statistically significant differences in LGE assessed using the FB-LGE versus conventional LGE on a per-segment (P = 0.42) and per-patient (P = 0.06) basis. Interobserver variability in LGE assessment for FB-LGE was good for per-segment (= 0.71) and per-patient extent (ICC = 0.92) analyses. ConclusionsThe accelerated FB-LGE sequence performed comparably to the conventional standard-of-care LGE sequence in a cohort of patients post COVID-19 infection in a fraction of the time and without the need for breath-holding. Such a sequence could impact clinical practice by increasing cardiac MRI throughput and accessibility for frail or acutely ill patients unable to perform breath-holding.

Feasibility of gray-blood late gadolinium enhancement evaluation in young patients with congenital and acquired heart disease.

Late gadolinium enhancement (LGE) sequences have become common in pediatric cardiovascular magnetic resonance (CMR) to assess for myocardial fibrosis. Bright-blood late gadolinium enhancement (BB-LGE) by conventional phase-sensitive inversion recovery (PSIR) is commonly utilized, but similar inversion time (TI) value of fibrosis and left ventricular (LV) blood pool can make subendocardial areas difficult to assess. A gray-blood LGE (GB-LGE) technique has been described, targeting nulling of the LV blood pool and demonstrating improvement in ischemic scar detection over BB-LGE in adult patients. We sought to evaluate the feasibility of the GB-LGE technique in a young population with congenital and acquired heart disease and compare its ability to detect subendocardial scar to conventional BB-LGE. Seventy-six consecutive patients referred for clinical CMR underwent both BB-LGE and GB-LGE on 1.5 T and 3 T scanners. Conventional PSIR sequences were obtained with TI to null the myocardium (BB-LGE) in short-axis and horizontal long-axis stacks. Same PSIR stacks were immediately repeated with TI to null the blood pool (GB-LGE). Both sequences were reviewed separately a week apart by two readers, blinded to the initial clinical interpretation. Studies were analyzed for overall image quality, confidence in scar detection, confidence in detection of LGE, LGE class, inter- and intra-observer agreement for the presence of scar, and intraclass correlation coefficient (ICC) for total scar burden. Overall confidence in myocardial scar detection by BB-LGE or GB-LGE as well as grading of image quality were not statistically different [(p = 1 and p = 1) and (p = 0.53, p = 0.18), respectively]. There was very good inter-observer agreement for the presence of scar on BB-LGE (K = 0.88, 95% CI 0.77-0.99) and GB-LGE (K = 0.84, 95% CI 0.7-0.96), as well as excellent intra-observer agreement for both readers (K = 0.93, 95% CI 0.87-0.99; and K = 0.81, 95% CI 0.69-0.95). Interclass correlation coefficient for total scar burden was excellent for BB-LGE (ICC = 0.98, 95% CI 0.96-0.99) and GB-LGE (ICC = 0.94, 95% CI 0.91-0.97). The GB-LGE technique is feasible in the pediatric population with congenital and acquired heart disease. It can detect subendocardial/ischemic scar similar to conventional bright-blood PSIR sequences in the pediatric population.

Differences in atrial substrate localization using late gadolinium enhancement-magnetic resonance imaging, electrogram voltage, and conduction velocity: a cohort study using a consistent anatomical reference frame in patients with persistent atrial fibrillation.

Electro-anatomical voltage, conduction velocity (CV) mapping, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) have been correlated with atrial cardiomyopathy (ACM). However, the comparability between these modalities remains unclear. This study aims to (i) compare pathological substrate extent and location between current modalities, (ii) establish spatial histograms in a cohort, (iii) develop a new estimated optimized image intensity threshold (EOIIT) for LGE-MRI identifying patients with ACM, (iv) predict rhythm outcome after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF). Thirty-six ablation-naive persistent AF patients underwent LGE-MRI and high-definition electro-anatomical mapping in sinus rhythm. Late gadolinium enhancement areas were classified using the UTAH, image intensity ratio (IIR >1.20), and new EOIIT method for comparison to low-voltage substrate (LVS) and slow conduction areas <0.2 m/s. Receiver operating characteristic analysis was used to determine LGE thresholds optimally matching LVS. Atrial cardiomyopathy was defined as LVS extent ≥5% of the left atrium (LA) surface at <0.5 mV. The degree and distribution of detected pathological substrate (percentage of individual LA surface are) varied significantly (P < 0.001) across the mapping modalities: 10% (interquartile range 0-14%) of the LA displayed LVS <0.5 mV vs. 7% (0-12%) slow conduction areas <0.2 m/s vs. 15% (8-23%) LGE with the UTAH method vs. 13% (2-23%) using IIR >1.20, with most discrepancies on the posterior LA. Optimized image intensity thresholds and each patient's mean blood pool intensity correlated linearly (R2 = 0.89, P < 0.001). Concordance between LGE-MRI-based and LVS-based ACM diagnosis improved with the novel EOIIT applied at the anterior LA [83% sensitivity, 79% specificity, area under the curve (AUC): 0.89] in comparison to the UTAH method (67% sensitivity, 75% specificity, AUC: 0.81) and IIR >1.20 (75% sensitivity, 62% specificity, AUC: 0.67). Discordances in detected pathological substrate exist between LVS, CV, and LGE-MRI in the LA, irrespective of the LGE detection method. The new EOIIT method improves concordance of LGE-MRI-based ACM diagnosis with LVS in ablation-naive AF patients but discrepancy remains particularly on the posterior wall. All methods may enable the prediction of rhythm outcomes after PVI in patients with persistent AF.

Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning

BackgroundMitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased mortality in MVP. ObjectivesThe authors sought to evaluate whether electrocardiogram (ECG)-based machine learning can identify MVP at risk for ComVE, death and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. MethodsA deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients from the University of California-San Francisco between 2012 and 2020. A separate CNN was trained to detect late gadolinium enhancement (LGE) using 1,369 ECGs from 87 MVP patients with contrast CMR. ResultsThe prevalence of ComVE was 28% (160/569). The area under the receiver operating characteristic curve (AUC) of the CNN to detect ComVE was 0.80 (95% CI: 0.77-0.83) and remained high after excluding patients with moderate-severe mitral regurgitation [0.80 (95% CI: 0.77-0.83)] or bileaflet MVP [0.81 (95% CI: 0.76-0.85)]. AUC to detect all-cause mortality was 0.82 (95% CI: 0.77-0.87). ECG segments relevant to ComVE prediction were related to ventricular depolarization/repolarization (early-mid ST-segment and QRS from V1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 24% patients with available CMR; AUC for detection of LGE was 0.75 (95% CI: 0.68-0.82). ConclusionsCNN-analyzed 12-lead ECGs can detect MVP at risk for ventricular arrhythmias, death and/or fibrosis and can identify novel ECG correlates of arrhythmic risk. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

225 PROGNOSTIC ROLE OF EARLY CARDIAC MAGNETIC RESONANCE IN MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES (MINOCA)

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a significant proportion of acute myocardial infarction (AMI) population. MINOCA is a working diagnosis and an accurate investigation of the underlying causes should always be performed. In this setting, cardiac magnetic resonance (CMR) imaging plays a pivotal diagnostic role. However, a prognostic stratification based on the CMR findings in ischemic MINOCA is still unavailable. Purpose To evaluate the potential prognostic impact of specific CMR findings - especially ischemic late gadolinium enhancement (LGE) patterns - in order to look for measurable parameters that may guide the management of this still troubled clinical entity. Methods We assessed 461 MINOCA from January 2016 to June 2021. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR findings, MINOCA were classified in two phenotypes: LGE-positive (an ischemic subendocardial or transmural LGE pattern) or LGE-negative (cases without LGE but exhibiting regional myocardial injury defined by myocardial edema in a coronary territory with a typically ischemic "wave-front" and/or regional wall motion abnormality consistent with coronary distribution). All-cause mortality, re-infarction, stroke, heart failure (HF) and the composite endpoint (MACE) were evaluated. Extended LGE was considered as the presence of &amp;gt;2 segments with transmural LGE. The mean follow-up was 36.1 ± 15.2 months and CMR was performed at a mean of 6 ± 2.9 days from the acute presentation. Results The final cohort included 175 MINOCA with a likely-ischemic etiology: 121 (69.1%) constituted the LGE-positive group. The mean age of the study population was 62.3 ± 12.9 years and more than 61% were females. During follow-up, HF (15.7% vs 1.9%, p=0.008) and MACE (20.7% vs 7.4%, p=0.029) occurred more frequently in MINOCA "LGE-positive" compared to the "LGE-negative" ones. Extended LGE was significantly more prevalent in patients with versus without subsequent HF. On multivariable Cox regression, extended LGE was an independent predictor of HF occurrence (HR 18.49, 95%CI 4.65–73.61, p &amp;lt; 0.001) and MACE (HR 14.64, 95%CI 3.91–54.86, p &amp;lt; 0.001). Conclusions Our data suggest that in MINOCA patients the detection of LGE is correlated with the incidence of major cardiovascular events and heart failure during long-term follow-up. In fact, LGE extension was identified as the strongest predictor of cardiac adverse events. The early execution of CMR is useful in the prognostic stratification of MINOCA and this could guide the subsequent clinical and therapeutic management.

Image Quality of Submillimeter High-Spatial-Resolution 2D Late Gadolinium-enhanced Images in Cardiac MRI: A Feasibility Study.

To evaluate the image quality of high-spatial-resolution two-dimensional (2D) late gadolinium enhancement (LGE) cardiac MRI compared with conventional normal-resolution LGE MRI. This prospective study included participants suspected of having cardiomyopathy who underwent cardiac MRI between March 2021 and December 2021. Normal-resolution and high-resolution 2D LGE sequences (inversion recovery [IR] and phase-sensitive inversion recovery [PSIR]) were performed at 3 T. Resolution was compared between normal-resolution and high-resolution images obtained in a quality assurance phantom. In vivo image quality and resolution were evaluated qualitatively using a five-point scoring system. Receiver operating characteristic curve analysis was used for LGE detection performance. Border sharpness was assessed with profile curve measurement. The contrast-to-noise ratio (CNR) between hyperenhancement and remote myocardium and LGE detection performance were calculated using normal-resolution IR images as the reference. In total, 120 participants were evaluated (mean age, 56 years ± 17 [SD]; 72 men). Features smaller than 1 mm were detectable only on high-resolution images of the phantom. In vivo, the image resolution score with high-resolution LGE was 4.14-4.24, which was higher than the normal-resolution LGE reference score of 2.99 (P < .05). Border sharpness was higher in high-resolution images (P < .001). Receiver operating characteristic curve analysis revealed no evidence of a difference in LGE detection between normal-resolution and high-resolution images. There was also no evidence of a change in CNR of LGE in IR and PSIR magnitude compared with reference images. Comparison of image quality in 2D high-resolution and normal-resolution LGE cardiac MRI demonstrated the highest resolution for high-resolution IR and high-resolution PSIR magnitude sequences.Keywords: Cartilage Imaging, MRI, Cardiac, Heart, Imaging Sequences, Comparative Studies Supplemental material is available for this article. © RSNA, 2022.

Cardiac involvement in creatine deficiency syndrome

Abstract Background Previous reports have demonstrated electrocardiographic and echocardiographic abnormalities consistent with early-stage cardiomyopathy in patients with creatine transporter (CrT) deficiency, but cardiac involvement has never been accurately characterized. Purpose To investigate the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS). Methods Wild type and transgenic CrT−/y mice (n=20) were serially evaluated in vivo by electrocardiogram (EKG) and echocardiography for six months, and ex vivo by histological and biochemical analyses. Nine patients with CDS (n=4 with L-arginine:glycine amidinotransferase - AGAT- deficiency, n=5 with CrT deficiency) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR). Results Compared to wild type, CRT−/y mice showed a prolongation of QT interval (p=0.008) (Fig. 1), as well as significant reduction in cardiac ATP production from mitochondria (p&amp;lt;0.001) (Fig. 2). No differences were detected in the left ventricular systolic function, in terms of ejection fraction and global longitudinal strain, along the whole follow-up. Similarly, 3 patients with CrT deficiency also showed a prolonged QTc interval (median QTc 515 ms), while other 2 had a borderline QTc at Holter monitoring, while no tachyarrhythmias could be observed. No subject had abnormal systolic and diastolic function. At CMR, an increase of native T1 value was reported in the 4 subjects (median 1076 ms) with AGAT deficiency, 1 with an increase of extracellular volume matching with the detection of late gadolinium enhancement. Finally, subjects with AGAT deficiency showed an increase level of plasma norepinephrine. Familiar carriers (3 for AGAT and 1 for CrT) showed no notable cardiac functional alterations, except for QTc prolongation in 2 subjects. Conclusion Prolonged QT interval is observed in the murine model and in subjects with CrT deficiency. Biohumoral signs of neurohormonal activation and an initial replacement fibrosis – the latter suggested by the increase of native T1 – are identified in subjects with AGAT deficiency, but their clinical significance remains to be determined. Funding Acknowledgement Type of funding sources: None.

Prognostic role of early cardiac magnetic resonance in myocardial infarction with non-obstructive coronary arteries

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a significant proportion of acute myocardial infarction (AMI) population. MINOCA is a working diagnosis and an accurate investigation of the underlying causes should always be performed. In this setting, cardiac magnetic resonance (CMR) imaging plays a pivotal diagnostic role. However, a prognostic stratification based on the CMR findings in ischemic MINOCA is still unavailable. Purpose To evaluate the potential prognostic impact of specific CMR findings - especially ischemic late gadolinium enhancement (LGE) patterns - in order to look for measurable parameters that may guide the management of this still troubled clinical entity. Methods We assessed 461 MINOCA from January 2016 to June 2021. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR findings, MINOCA were classified in two phenotypes: LGE-positive (an ischemic subendocardial or transmural LGE pattern) or LGE-negative (cases without LGE but exhibiting regional myocardial injury defined by myocardial edema in a coronary territory with a typically ischemic “wave-front” and/or regional wall motion abnormality consistent with coronary distribution). All-cause mortality, re-infarction, stroke, heart failure (HF) and the composite endpoint (MACE) were evaluated. Extended LGE was considered as the presence of &amp;gt;2 segments with transmural LGE. The mean follow-up was 36.1±15.2 months and CMR was performed at a mean of 6±2.9 days from the acute presentation. Results The final cohort included 175 MINOCA with a likely-ischemic etiology: 121 (69.1%) constituted the LGE-positive group. The mean age of the study population was 62.3±12.9 years and more than 61% were females. During follow-up, HF (15.7% vs 1.9%, p=0.008) and MACE (20.7% vs 7.4%, p=0.029) occurred more frequently in MINOCA “LGE-positive” compared to the “LGE-negative” ones. Extended LGE was significantly more prevalent in patients with versus without subsequent HF. On multivariable Cox regression, extended LGE was an independent predictor of HF occurrence (HR 18.49, 95% CI 4.65–73.61, p&amp;lt;0.001) and MACE (HR 14.64, 95% CI 3.91–54.86, p&amp;lt;0.001). Conclusions Our data suggest that in MINOCA patients the detection of LGE is correlated with the incidence of major cardiovascular events and heart failure during long-term follow-up. In fact, LGE extension was identified as the strongest predictor of cardiac adverse events. The early execution of CMR is useful in the prognostic stratification of MINOCA and this could guide the subsequent clinical and therapeutic management. Funding Acknowledgement Type of funding sources: None.

Right ventricular longitudinal strain on CMR predicts ventricular arrhythmias and mortality in cardiac sarcoidosis

BackgroundRight ventricular (RV) dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias (VA) and mortality in cardiac sarcoidosis (CS). However, image resolution limits the detection of RV LGE. Global longitudinal RV strain (RVS) correlates to RV scar on electroanatomical mapping and RV function. ObjectiveWe evaluated the association between RVS on CMR and VA/death (combined-primary-endpoint (CPE)) in patients with CS. MethodsRVS and RV LGE on MRI were retrospectively compared to variables known to predict outcomes in 66 patients with CS. Outcomes were obtained from electronic medical records and implantable cardioverter defibrillator (ICD) interrogations over median [IQR] 3.7[1.7, 6.3] years. Cox proportional hazard models were used to evaluate survival. Harrell's C-statistic was used to compare variables in risk prediction models. Results62.1 % of patients were male, with a mean age [SD] of 52.3 [9.6] years and left ventricular ejection fraction (LVEF) of 51.1[17.5]%. 9 patients with the primary endpoint were more likely to be Caucasian (p = 0.01) with prior VAs (p = 0.002), be on anti-arrhythmic drugs (p = 0.001) with an ICD (p = 0.002). In multivariable analyses adjusted for age, race, and history of VA, RVS (1.18 [1.05–1.31], p = 0.004), RV EDVI (1.08[1.01, 1.14], p = 0.02), and LV LGE (1.07[1.00, 1.13], p = 0.04) predicted the CPE. Risk prediction models including RVS (Cstatistic 0.94), outperformed those including RV and LV LGE (0.89–0.92). ConclusionRVS on CMR was the best predictor of VA and mortality in CS.

Abstract P217: Cardiac Involvement In Creatine Deficiency Syndrome: From Transgenic Model To Humans

Background: Electrocardiographic/echocardiographic abnormalities consistent with early-stage cardiomyopathy were previously reported in creatine transporter (CrT) deficiency. Nevertheless, cardiac involvement has never been accurately characterized. Aim: widen the current knowledge of the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS). Methods: Wild type and transgenic CrT -/y mice (n=20) were serially evaluated in vivo by electrocardiogram (EKG) and echocardiography for 6 months, and ex vivo by histological/biochemical analyses. Nine patients with CDS (n=4 with L-arginine:glycine amidinotransferase - AGAT- deficiency, n=5 with CrT deficiency) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR). Results: Compared to wild type, CrT -/y mice showed a prolongation of QT interval (p=0.008) associated with a lower expression of ATPase sarcoplasmic/endoplasmic reticulum Ca 2+ transporting 2, involved in turn in intracellular Ca 2+ homeostasis. The significant reduction in mitochondrial ATP rate production (p&lt;0.001) was attributed to a limited availability of ketone bodies, whereas ATP synthase F1 subunit alpha was not affected. No differences were detected in the left ventricular systolic function, neither by 2D-echo nor by speckle tracking. A prolonged QTc interval, detected in 7 patients at Holter monitoring, was mainly detected in case of CrT deficiency, without evidence of tachyarrhythmias. Although no impairment of cardiac function was detected at CMR, only subjects with AGAT deficiency showed an increase level of plasmatic norepinephrine and of native T1 value - 1 with an increase of extracellular volume, matching with the detection of late gadolinium enhancement. Conclusion: Prolonged QT interval is observed in murine model - even with a slightly impaired metabolism - and in subjects with CrT deficiency. Biohumoral signs of neurohormonal activation and an initial replacement fibrosis - the latter suggested by the increase of native T1 - are identified in subjects with AGAT deficiency, but their clinical significance remains to be determined.

P241 CARDIAC INVOLVEMENT IN CREATINE DEFICIENCY SYNDROME

Abstract Background Previous reports have demonstrated electrocardiographic and echocardiographic abnormalities consistent with early–stage cardiomyopathy, in patients with creatine transporter deficiency (CRT–D), but cardiac involvement has never been accurately characterized. Our aim was to widen the current knowledge of the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS). Methods Wild type (n = 6) and transgenic CRT–/y mice (n = 6) were evaluated in vivo by electrocardiogram (EKG) and echocardiography for six months, and ex vivo by histological and biochemical analyses. Nine patients with CDS (4 with L–arginine:glycine amidinotransferase deficiency – AGAT–D, 5 with CRT–D) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR). Results Compared to wild–type, CRT–/y mice showed a prolongation of QT interval (p = 0.008) (Fig. 1), as well as a trend of reduction of mitochondrial function (Fig. 2). No differences were dected in the left ventricular systolic function, in terms of ejection fraction and global longitudinal strain, at different times. Aldosterone levels were also not different between the two groups. Three patients with CDS also showed a prolonged QTc interval (median QTc 515 ms), while other 3 had a borderline QTc at Holter monitoring, without tachyarrhythmias. No subject had abnormal systolic and diastolic function. At CMR, an increase of native T1 value was reported in 4 subjects (median 1076 ms), 1 with an increase of extracellular volume matching with the detection of late gadolinium enhancement. Finally, 7 subjects with CDS presented with biohumoral signs of neurohormonal activation (2 with elevated renin, 1 with increased aldosterone and 4 with increased norepinephrine levels). Familiar carriers (3 for AGAT–D and 1 for CRT–D) showed no notable cardiac functional alterations, except for QTc prolongation in 2 AGAT–D carriers. Conclusion Prolonged QT interval is observed in a murine model of CRT–D deficiency and in patients with CDS, in absence of an arrhythmic burden. No alterations in cardiac function were detected in the two setting, except for an increase of native T1 in patients with CDS suggesting an interstitial and replacement fibrosis.

The image quality and diagnostic accuracy of T1-mapping-based synthetic late gadolinium enhancement imaging: comparison with conventional late gadolinium enhancement imaging in real-life clinical situation

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

Abstract 13321: Identifying Mitral Valve Prolapse at Risk for Ventricular Arrhythmias and Myocardial Fibrosis From 12-lead ECGs Using Deep Learning

Background: Inferior biphasic or inverted T waves have been described on a standard 12-lead ECG in some, but not all patients with malignant mitral valve prolapse (MVP). In contrast, complex ventricular ectopy (ComVE) is associated with myocardial fibrosis and increased mortality in MVP and may represent a better marker of arrhythmic risk. We hypothesize that an ECG-based machine-learning model can identify MVP with ComVE and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging within a large ECG database beyond traditional ECG criteria. Methods: A deep convolutional neural network (DNN) was trained to detect ComVE using 12 leads in 6,916 ECGs from 569 MVP patients evaluated at the University of California San Francisco (UCSF) between 2012 and 2020. A DNN was also trained using 87 UCSF MVP patients with available contrast CMR to detect late gadolinium enhancement (LGE). Results: The prevalence of ComVE was 160/569 or 28% (20 or 3% with cardiac arrest or sudden arrhythmic death). The area under the curve (AUC) of the DNN to detect ComVE was 0.81 (95% CI, 0.78-0.84) (Figure). AUC remained high even after excluding patients with moderate-severe mitral regurgitation (MR) [0.80 (95% CI, 0.77-0.83)], or with bileaflet MVP [0.81 (95% CI, 0.76-0.85)]. The top ECG segments able to discriminate ComVE vs no ComVE were related to ventricular depolarization and repolarization (early-mid ST and QRS fromV1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 22 of 87 (25%) with available CMR. The AUC for detection of LGE was 0.75 (95% CI, 0.68-0.82). Conclusions: A deep-learning model can detect MVP at risk for ventricular arrhythmias and fibrosis from standard 12-lead ECGs, and can identify novel ECG correlates of arrhythmic risk regardless of leaflet involvement or mitral regurgitation severity. ECG-based deep-learning may help select, within a large echocardiographic database, those MVP patients requiring closer follow-up and/or a CMR.

B-PO05-118 RIGHT VENTRICULAR LONGITUDINAL STRAIN ON CMR PREDICTS VENTRICULAR ARRHYTHMIC AND MORTALITY IN CARDIAC SARCOIDOSIS

Ventricular arrhythmias (VA) are a leading cause of death in patients with cardiac sarcoidosis (CS). Right ventricular (RV) dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) have been linked to incidence of VAs. However, detection of LGE of the RV is limited by image resolution. Global longitudinal RV strain (RVS) correlates to RV scar on electroanatomical mapping, and is a valid measure of regional RV function. We evaluated the association between RVS on CMR and incidence of VAs, cardiovascular (CV) death, and heart transplantation (HT) (combined primary end-point) in patients with CS. In this retrospective study, 71 patients with probable or definite CS were included. RVS and RV LGE on MRI were compared to variables known to predict arrhythmic and mortality outcomes in CS. Outcomes were obtained by review of electronic medical records and cardiac implantable electronic device interrogations over a median [IQR] follow-up period of 3.7[1.7, 6.3) years. Cox proportional hazard models were used to evaluate the probability of event-free survival. Harrell’s C statistic was used to compare variables in risk prediction models. 59% of patients were male, with median age [IQR] of 52.3 [42.4, 62.2] years, and left ventricular ejection fraction (LVEF) of 54.9%[41.4, 68.4]. During the follow-up period, 13 patients developed the primary endpoint and were more likely to have a history of Vas (HR[95% CI] 6.80[1.86,24.8],p=0.004) and higher LV LGE burden (1.07[1.01,1.12], p=0.02). In a multivariate analysis adjusted for age, race, and history of VA, decreased RVS was a significant predictor of the primary outcome (0.84[0.71, 0.98], p=0.03), whereas RV LGE, RV end-diastolic volume (EDV) and RV EF were not. Risk prediction models including RVS (Harrell’s C statistic 0.87) were superior to those including only RV LGE (0.79) or LV LGE burden (0.82). Global RVS on CMR was the best predictor of VAs or CV death in patients with CS.

3D Dixon water-fat LGE imaging with image navigator and compressed sensing in cardiac MRI

ObjectivesTo evaluate an image-navigated isotropic high-resolution 3D late gadolinium enhancement (LGE) prototype sequence with compressed sensing and Dixon water-fat separation in a clinical routine setting.Material and methodsForty consecutive patients scheduled for cardiac MRI were enrolled prospectively and examined with 1.5 T MRI. Overall subjective image quality, LGE pattern and extent, diagnostic confidence for detection of LGE, and scan time were evaluated and compared to standard 2D LGE imaging. Robustness of Dixon fat suppression was evaluated for 3D Dixon LGE imaging. For statistical analysis, the non-parametric Wilcoxon rank sum test was performed.ResultsLGE was rated as ischemic in 9 patients and non-ischemic in 11 patients while it was absent in 20 patients. Image quality and diagnostic confidence were comparable between both techniques (p = 0.67 and p = 0.66, respectively). LGE extent with respect to segmental or transmural myocardial enhancement was identical between 2D and 3D (water-only and in-phase). LGE size was comparable (3D 8.4 ± 7.2 g, 2D 8.7 ± 7.3 g, p = 0.19). Good or excellent fat suppression was achieved in 93% of the 3D LGE datasets. In 6 patients with pericarditis, the 3D sequence with Dixon fat suppression allowed for a better detection of pericardial LGE. Scan duration was significantly longer for 3D imaging (2D median 9:32 min vs. 3D median 10:46 min, p = 0.001).ConclusionThe 3D LGE sequence provides comparable LGE detection compared to 2D imaging and seems to be superior in evaluating the extent of pericardial involvement in patients suspected with pericarditis due to the robust Dixon fat suppression.Key Points• Three-dimensional LGE imaging provides high-resolution detection of myocardial scarring.• Robust Dixon water-fat separation aids in the assessment of pericardial disease.• The 2D image navigator technique enables 100% respiratory scan efficacy and permits predictable scan times.

Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction

PurposeTo test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). MethodsWe selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. ResultsOverall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (−20.1 ± 3.1% vs −21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (−19.7 ± 2.9% vs −21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was −21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was −16.4%. ConclusionsAt CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.

Validation of black blood late gadolinium enhancement (LGE) for evaluation of myocardial infarction in patients with or without pathological Q-wave on electrocardiogram (ECG).

The pathological Q-wave (QW) is an important indicator of infarcted myocardial volume indicating a worse prognosis compared to non-Q-wave (NQW) infarctions. Traditional classification divides infarcts into transmural and non-transmural based on QW and NQW. This view has been challenged by the advent of late gadolinium enhancement (LGE) MR imaging. Conventional LGE (Conv-LGE) detection of subendocardial MI is limited by bright blood pool. Dark Blood LGE imaging (DB-LGE) nulls the blood pool improving the conspicuity and accuracy of detection of subendocardial infarcts. We hypothesize that improved detection of subendocardial enhancement with DB-LGE will result in improved correlation of electrocardiogram (ECG) and extent of infarction. Sixty-four clinically confirmed infarction patients were enrolled in this prospective study. All the participants underwent cardiac MR imaging including conv-LGE and DB-LGE. Twelve-lead ECG were performed on the same day. The patients were divided into QW and NQW groups by one experienced cardiologist. MI quantitation was by MI% (the ratio of MI volume to whole myocardial volume) and transmural grading, compared using paired t-test and Wilcoxon-test, respectively. The image quality obtained by Conv-LGE and DB-LGE were evaluated according to the signal intensity ratio (SIR) and contrast-to-noise ratio (CNR). Fifty-six subjects were enrolled in the final analysis [23 (41%) QW and 33 (59%) NQW infarcts]. For the QW cohort, both sequences classified infarcts as transmural in 21/23 (91%) subjects and subendocardial in 2/23 (9%). For the NQW cohort, both sequences classified infarcts as transmural in 16/33 (48%) subjects and subendocardial in 17/33 (52%). Using BB-LGE there were significant differences in detecting subendocardial infarcts in QW and NQW cohorts (Z=-5.85, P<0.001). The MI% of QW group was greater than in NQW group (24.2±10.3 vs.15.9±9.8, P=0.003). Compared to Conv-LGE, BB-LGE provided higher CNR and SIR between infarcted myocardium and blood pool (6.3±2.6 vs. 2.1±1.3, P<0.001; 5.4±1.9 vs. 1.3±0.2, P<0.001). BB-LGE detected more subendocardial infarcted segments in the QW group and NQW group (Z=-4.24, P<0.001; Z=-5.57, P<0.001). The larger MI% was displayed in BB-LGE than in Conv-LGE in both QW group and NQW group (24.2±10.3 vs. 22.6±10.3, P<0.001; 15.9±9.8 vs.14.6±9.6, P=0.001). Compared to conventional LGE, DB-LGE can provide more accurate detection and characterization of infarction in terms of transmurality and subendocardial extent. This is important for evaluating QW and NQW MIs. Due to nulling the high signal of blood pool, DB-LGE can effectively improve the identification of subendocardial MI which may be missed on conventional LGE. Therefore, in both QW and NQW MIs, DB-LGE detects more subendocardial MIs and larger MI% is found. This may facilitate more accurate quantitative MR assessment of both QW and NQW MIs and further empower LGE volume as a predictive biomarker.

P5253Does regional myocardial strain by cardiac magnetic resonance feature tracking reflect scar in ischemic heart disease?

Abstract Background Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) is the gold standard for detection of myocardial scar. We hypothesized that CMR Feature Tracking (FT)-derived regional myocardial strain may reflect the presence of scar and could thus potentially be used instead of LGE imaging. Purpose The aim of this study was to determine the relationship between FT-derived regional myocardial strain and LGE in patients with coronary artery disease (CAD). Methods Seventy-five patients with CAD and typical ischemic LGE patterns on CMR (1.5T) were included (mean age 60±12 years, 70% males). Myocardial strain analysis and LGE identification were performed using dedicated commercial software. Scar was defined by presence of LGE in the same area of the myocardium in both short- and long-axis views. Peak systolic regional longitudinal and circumferential strain (RLS, RCS) values were calculated in the region of interest corresponding to the LGE area and also in a non-LGE myocardial region as a reference in each patient. These comparisons were repeated for a subgroup of 36 patients with left ventricular (LV) ejection fraction (EF) &lt;40% to determine whether the relationship between strain and LGE holds in the presence of reduced LV function, when strain measurements may be altered as a reflection of reduced LVEF itself. Results Both global longitudinal and circumferential strain values were abnormal (−12.8±5.1% and −11.4±4.1%, respectively), reflecting LV dysfunction in this CAD cohort (EF = 40±16%). The magnitude of both RLS and RCS was significantly reduced in areas of LGE, compared to those without LGE: RLS −10.0±5.8% versus −20.4±7.5% (p&lt;0.001); RCS −10.1±5.3±% versus −18.9±7.5%, respectively (p&lt;0.001). Same pattern was noted in the reduced EF subgroup: RLS −8.0±4.7% versus −16.9±6.6% (p&lt;0.001), RCS −7.7±4.3±% versus −16.0±7.9%, respectively (p&lt;0.001). The figure depicts 2 representative cases in long and short axis views, LGE detection and concomitant regional strain analysis. LGE and regional strain analysis. Conclusion Reduced magnitude of regional longitudinal and circumferential strain by CMR-FT correlates with presence of LGE. Pending further validation, this finding may constitute the basis for detection of scar without contrast enhanced imaging, and would result in reduced cost, scan time and risk associated with gadolinium. Acknowledgement/Funding ARP: Research support (software) from Neosoft and Philips

Intensity and Distribution of Patchy Late Gadolinium Enhancement in Left Atrium in Patients With Atrial Fibrillation.

Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) studies were performed on healthy individuals to establish signal intensity thresholds for reproducible left atrial (LA) patchy LGE detection. Using established criteria, differences in LA patchy LGE between healthy volunteers (HV) and patients with atrial fibrillation (AF) or hypertension were analyzed. Fifty-three patents with AF (mean age 56 years, 60% men), 25 patients with hypertension and no history of AF (mean age 54 years, 40% men), and 28 HV (mean age 50 years, 52% men) were enrolled in an observational, non-interventional, case-control prospective study. LA patchy LGE quantification was performed using LGE MRI (1.5 T scanner, voxel size 1.25x1.25x2.5 mm) and the custom-built software based on estimation of LA voxel image intensity ratio and comparison with threshold value obtained from HV data. Based on analysis of healthy individuals' data, the optimal threshold value for the left atrial patchy LGE quantification was determined at 1.38. Patients with AF had a higher extent of LA patchy LGE (9.1 [1.72; 18.58] %) than patients with hypertension (3.81 [0.57; 9.51] %) and HV (0.78 [0.05; 3.5] %). The predominant location of LA patchy LGE in AF was in the pulmonary vein ostia region, in hypertension - LA posterior wall, and in HV - lower part of LA posterior wall. In AF patients, the extent of LA patchy LGE correlated with LA end-diastolic volume (r=0.37) and LA ejection fraction (r=-0.4), in HV - with age (r=0.66) and LA end-diastolic volume (r=0.4). AF and hypertension are associated with higher extent and different location of LA patchy LGE compared to changes caused by natural aging. The extent of LA patchy enhancement correlates with LA dilatation.