Dataset Information

Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate.

ABSTRACT:

Background

Nivolumab is a human IgG4 anti-programmed cell death protein-1 (PD-1) monoclonal antibody that works by augmenting the immune response against tumour cells. It has the potential of causing multiple autoimmune-related events, including cardiac. However, the real incidence and diagnosis of cardiac complications remains unclear.

Case summary

A 47-year-old woman with a history of carotid artery dissection and metastatic melanoma presented with acute heart failure. One year prior to presentation, she had received one cycle only of checkpoint inhibitor therapy with both ipilimumab and nivolumab, and nivolumab only was restarted 4 months prior to presentation. On admission, she was hypotensive, tachycardic due to atrial tachycardia and with pulmonary oedema. An echocardiogram revealed a left ventricular ejection fraction of 26%. Cardiovascular magnetic resonance (CMR) demonstrated a non-ischaemic pattern of late gadolinium enhancement (LGE), most consistent with myocarditis. The diagnosis of immunotherapy-mediated cardiac toxicity was highly considered and immunosuppressive therapy was initiated. However, she went into refractory cardiogenic shock and did not survive. An autopsy performed with samples from areas of myocardium with and without LGE on the CMR, found correlation.

Discussion

According to the literature, cardiac complications develop in less than 1% of patients treated with checkpoint inhibitors, with a 0.06% incidence reported in nivolumab specifically. However, it may be higher, given the lack of cardiac monitoring during treatment. We present the first case demonstrating direct histological correlation of T-lymphocytic infiltration with areas of LGE on CMR. Future investigation using CMR for early detection of inflammation and left ventricular dysfunction may help to diagnosis disease earlier.

SUBMITTER: Gallegos C

PROVIDER: S-EPMC6439394 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate.

Gallegos Cesia C Rottmann Douglas D Nguyen Vinh Q VQ Baldassarre Lauren A LA

European heart journal. Case reports 20190107 1

<h4>Background</h4>Nivolumab is a human IgG4 anti-programmed cell death protein-1 (PD-1) monoclonal antibody that works by augmenting the immune response against tumour cells. It has the potential of causing multiple autoimmune-related events, including cardiac. However, the real incidence and diagnosis of cardiac complications remains unclear.<h4>Case summary</h4>A 47-year-old woman with a history of carotid artery dissection and metastatic melanoma presented with acute heart failure. One year ...[more]

PMID: 31020225

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Project description:PurposeTo develop a free-breathing whole-heart isotropic-resolution 3D late gadolinium enhancement (LGE) sequence with Dixon-encoding, which provides co-registered 3D grey-blood phase-sensitive inversion-recovery (PSIR) and complementary 3D fat volumes in a single scan of < 7 min.MethodsA free-breathing 3D PSIR LGE sequence with dual-echo Dixon readout with a variable density Cartesian trajectory with acceleration factor of 3 is proposed. Image navigators are acquired to correct both inversion recovery (IR)-prepared and reference volumes for 2D translational respiratory motion, enabling motion compensated PSIR reconstruction with 100% respiratory scan efficiency. An intermediate PSIR reconstruction is performed between the in-phase echoes to estimate the signal polarity which is subsequently applied to the IR-prepared water volume to generate a water grey-blood PSIR image. The IR-prepared water volume is obtained using a water/fat separation algorithm from the corresponding dual-echo readout. The complementary fat-volume is obtained after water/fat separation of the reference volume. Ten patients (6 with myocardial scar) were scanned with the proposed water/fat grey-blood 3D PSIR LGE sequence at 1.5 T and compared to breath-held grey-blood 2D LGE sequence in terms of contrast ratio (CR), contrast-to-noise ratio (CNR), scar depiction, scar transmurality, scar mass and image quality.ResultsComparable CRs (p = 0.98, 0.40 and 0.83) and CNRs (p = 0.29, 0.40 and 0.26) for blood-myocardium, scar-myocardium and scar-blood respectively were obtained with the proposed free-breathing 3D water/fat LGE and 2D clinical LGE scan. Excellent agreement for scar detection, scar transmurality, scar mass (bias = 0.29%) and image quality scores (from 1: non-diagnostic to 4: excellent) of 3.8 ± 0.42 and 3.6 ± 0.69 (p > 0.99) were obtained with the 2D and 3D PSIR LGE approaches with comparable total acquisition time (p = 0.29). Similar agreement in intra and inter-observer variability were obtained for the 2D and 3D acquisition respectively.ConclusionThe proposed approach enabled the acquisition of free-breathing motion-compensated isotropic-resolution 3D grey-blood PSIR LGE and fat volumes. The proposed approach showed good agreement with conventional 2D LGE in terms of CR, scar depiction and scan time, while enabling free-breathing acquisition, whole-heart coverage, reformatting in arbitrary views and visualization of both water and fat information.

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

Project description:ObjectiveThe aims of our study were to investigate the effect of the extent and location of late gadolinium enhancement (LGE) on the left atrium (LA) function in patients with acute myocarditis (AM) using cardiovascular magnetic resonance (CMR).MethodThis retrospective study performed CMR scans in 113 consecutive patients (89 males, 24 females; mean age 45.8 ± 17.3 years) with AM that met the updated Lake Louise criteria. Reservoir, conduit, and booster LA functions were analyzed by CMR feature tracking using dedicated software. Besides LA strain measurements, myocardial scar location and extent were assigned and quantified by LGE imaging.ResultsAM patients with septal LGE had impaired reservoir, conduit, and conduit strain rate function in comparison with AM patients with non-septal LGE (p = 0.001, for all). In fully adjusted multivariable linear regression, reservoir and conduit were significantly associated with left ventricle (LV) LGE location (β coefficient = 8.205, p = 0.007; β coefficient = 5.185, p = 0.026; respectively). In addition, LA parameters decreased according to the increase in the extent of LV fibrosis (LGE ≤ 10%; LGE 11-19%; LGE ≥ 20%). After adjustment in multivariable linear regression, the association with LV LGE extent was no longer statistically significant.ConclusionIn patients with acute myocarditis, LA function abnormalities are significantly associated with LV LGE location, but not with LGE extent. Septal LGE is paralleled by a deterioration of LA reservoir and conduit function.Clinical relevance statementLeft atrium dysfunction is associated with the presence of late gadolinium enhancement in the left ventricle septum and can be useful in the clinical prognostication of patients with acute myocarditis, allowing individually tailored treatment.Key points• Myocardial fibrosis is related to atrial impairment. • The location of myocardial fibrosis is the main determinant of atrial dysfunction in myocarditis patients. • The quantification of atrial mechanisms may provide more in-depth insight into myocarditis pathophysiology.

Project description:BackgroundConventional 2D inversion recovery (IR) and phase sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) have been widely incorporated into routine CMR for the assessment of myocardial viability. However, reliable suppression of fat signal, and increased isotropic spatial resolution and volumetric coverage within a clinically feasible scan time remain a challenge. In order to address these challenges, this work proposes a highly efficient respiratory motion-corrected 3D whole-heart water/fat LGE imaging framework.MethodsAn accelerated IR-prepared 3D dual-echo acquisition and motion-corrected reconstruction framework for whole-heart water/fat LGE imaging was developed. The acquisition sequence includes 2D image navigators (iNAV), which are used to track the respiratory motion of the heart and enable 100% scan efficiency. Non-rigid motion information estimated from the 2D iNAVs and from the data itself is integrated into a high-dimensional patch-based undersampled reconstruction technique (HD-PROST), to produce high-resolution water/fat 3D LGE images. A cohort of 20 patients with known or suspected cardiovascular disease was scanned with the proposed 3D water/fat LGE approach. 3D water LGE images were compared to conventional breath-held 2D LGE images (2-chamber, 4-chamber and stack of short-axis views) in terms of image quality (1: full diagnostic to 4: non-diagnostic) and presence of LGE findings.ResultsImage quality was considered diagnostic in 18/20 datasets for both 2D and 3D LGE magnitude images, with comparable image quality scores (2D: 2.05?±?0.72, 3D: 1.88?±?0.90, p-value?=?0.62) and overall agreement in LGE findings. Acquisition time for isotropic high-resolution (1.3mm3) water/fat LGE images was 8.0?±?1.4?min (3-fold acceleration, 60-88 slices covering the whole heart), while 2D LGE images were acquired in 5.6?±?2.2?min (12-18 slices, including pauses between breath-holds) albeit with a lower spatial resolution (1.40-1.75?mm in-plane ×?8?mm slice thickness).ConclusionA novel framework for motion-corrected whole-heart 3D water/fat LGE imaging has been introduced. The method was validated in patients with known or suspected cardiovascular disease, showing good agreement with conventional breath-held 2D LGE imaging, but offering higher spatial resolution, improved volumetric coverage and good image quality from a free-breathing acquisition with 100% scan efficiency and predictable scan time.

Dataset Information

Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate.

Background

Case summary

Discussion

Publications

Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate.

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