Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

OBJECTIVES: To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. METHODS: Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2 weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. RESULTS: The study protocol was completed in 110 participants (mean age, 62 years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). CONCLUSION: ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. CLINICAL RELEVANCE STATEMENT: ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. KEY POINTS: • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

Cardiac magnetic resonance-based layer-specific strain in immune checkpoint inhibitor-associated myocarditis.

AIMS: To assess the different imaging characteristics between corticosteroid-sensitive (CS) and corticosteroid-refractory (CR) immune checkpoint inhibitor-associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. METHODS AND RESULTS: Thirty-five patients diagnosed with ICIaM and 30 age and gender-matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub-endocardial (GLSendo) and sub-epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non-fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (-14.61 ± 2.67 vs. -18.50 ± 2.53, P < 0.001) and GLSepi (-14.75 ± 2.53 vs. -16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (-16.68 ± 2.05 vs. -19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE-positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189-3.962, P = 0.012). A GLSendo of ≥-17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan-Meier analysis showed that in patients with impaired GLSendo of ≥-17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <-17.10% (Log-rank test P = 0.017). CONCLUSIONS: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid-refractory individuals in the ICIaM population.

Diagnostic performance of 3.0 T unenhanced Dixon water-fat separation coronary MR angiography in patients with low-to-intermediate risk of coronary artery disease.

PURPOSE: To evaluate the diagnostic performance of 3.0 T unenhanced compressed-sensing sensitivity encoding (CS-SENSE) Dixon water-fat separation coronary MR angiography (CMRA) in patients with low-to-intermediate risk of coronary artery disease (CAD) and its ability to grade the severity of CAD based on Coronary Artery Disease Reporting and Data System (CAD-RADS). METHODS: A total of 55 patients who was clinically evaluated as low-to-intermediate risk of CAD were finally included to undergo both 3.0 T CS-SENSE water-fat separation CMRA and coronary computed tomography angiography (CCTA), and 11 of them also underwent X-ray coronary angiography (CAG). The severity of coronary artery disease was graded in patients who had completed both CCTA and CMRA examinations by the use of CAD-RADS reports for the patients with stable chest pain, and the diagnostic consistency between the two approaches was evaluated. Diagnostic performance of CMRA was assessed using the combination of CCTA and CAG as the reference standard for excluding or confirming CAD respectively. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 3.0 T unenhanced water-fat separation coronary MRA were 90.0%, 95.0%, 81.8%, 97.4% and 94.0% for a patient-based analysis respectively. In comparison with CCTA, 3.0 T Dixon water-fat separation CMRA demonstrated excellent consistency in grading the severity of coronary heart disease according to CAD-RADS (0.77 for kappa value). CONCLUSION: In the group of low-to-intermediate probability for CAD, 3.0 T unenhanced CS-SENSE Dixon water-fat separation CMRA can present satisfactory diagnostic performance for the exclusion of CAD with high sensitivity and negative predictive value as well as the evaluation of grading the severity of coronary artery disease.

A clinical strategy to improve the diagnostic performance of 3T non-contrast coronary MRA and noninvasively evaluate coronary distensibility: combination of diastole and systole imaging.

BACKGROUND: The clinical application of coronary MR angiography (MRA) combining diastole and systole imaging has never been described comprehensively in coronary artery disease (CAD) patients. We aimed to design an optimal non-contrast coronary MRA scan protocol combining diastolic and systolic imaging and to (1) evaluate its diagnostic performance for detecting significant coronary stenosis; (2) evaluate the feasibility of this protocol to noninvasively measure the coronary distensibility index (CDI). METHODS: From June 2021 to May 2022, 33 healthy volunteers and 91 suspected CAD patients scheduled for X-ray coronary angiography (CAG) were prospectively enrolled. 3T non-contrast water-fat coronary MRA was carried out twice at diastole and systole. Significant coronary stenosis was defined as a luminal diameter reduction of ≥ 50% using CAG as the reference and was evaluated as follows: (1) by coronary MRA in diastole alone; (2) by coronary MRA in systole alone; (3) by combined coronary MRA in diastole and systole. According to CAG, the patients were divided into significant CAD patients and non-significant CAD patients. The difference in CDI among participants was evaluated. RESULTS: Combined coronary MRA was completed in 31 volunteers and 76 patients. The per-patient sensitivity, specificity, and accuracy of combined coronary MRA were 97.5%, 83.3%, and 90.8%, respectively. Compared with single diastolic mode, combined coronary MRA showed equally high sensitivity but improved specificity on a per-patient basis (83.3% vs. 63.9%, adjusted P = 0.013). The CDI tested by coronary MRA decreased incrementally from healthy volunteers to non-significant and significant CAD patients. CONCLUSION: Compared with single-phase mode, 3 T non-contrast combined coronary MRA significantly improved specificity and may have potential to be a simple noninvasive method to measure CDI.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

3.0 T unenhanced Dixon water-fat separation whole-heart coronary magnetic resonance angiography: compressed-sensing sensitivity encoding imaging versus conventional 2D sensitivity encoding imaging.

This study was aimed to investigate 3.0 T unenhanced Dixon water-fat whole-heart CMRA (coronary magnetic resonance angiography) using compressed-sensing sensitivity encoding (CS-SENSE) and conventional sensitivity encoding (SENSE) in vitro and in vivo. The key parameters of CS-SENSE and conventional 1D/2D SENSE were compared in vitro phantom study. In vivo study, fifty patients with suspected coronary artery disease (CAD) completed unenhanced Dixon water-fat whole-heart CMRA at 3.0 T using both CS-SENSE and conventional 2D SENSE methods. We compared mean acquisition time, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and the diagnostic accuracy between two techniques. In vitro study, CS-SENSE achieved better effectiveness between higher SNR/CNR and shorter scan times using the appropriate acceleration factor compared with conventional 2D SENSE. In vivo study, CS-SENSE CMRA had better performance than 2D SENSE in terms of the mean acquisition time, SNR and CNR (7.4 ± 3.2 min vs. 8.3 ± 3.4 min, P = 0.001; SNR: 115.5 ± 35.4 vs. 103.3 ± 32.2; CNR: 101.1 ± 33.2 vs. 90.6 ± 30.1, P < 0.001 for both). The diagnostic accuracy between CS-SENSE and 2D SENSE had no significant difference on a patient-based analysis (sensitivity: 97.3% vs. 91.9%; specificity: 76.9% vs. 61.5%; accuracy: 92.0% vs. 84.0%; P > 0.05 for each). Unenhanced CS-SENSE Dixon water-fat separation whole-heart CMRA at 3.0 T can improve the SNR and CNR, shorten the acquisition time while providing equally satisfactory image quality and diagnostic accuracy compared with 2D SENSE CMRA.

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Detecting Regional Fibrosis in Hypertrophic Cardiomyopathy: The Utility of Myocardial Strain Based on Cardiac Magnetic Resonance.

RATIONALE AND OBJECTIVES: The value of myocardial strain for reflecting fibrosis in patients with hypertrophic cardiomyopathy (HCM) on cardiac magnetic resonance (CMR) has not been definite. We aim to explore whether there are underlying non-contrast parameters to evaluate myocardial fibrosis and screen which may be the best. MATERIALS AND METHODS: We retrospectively included 127 HCM patients (89 men; average age 46.6 ± 15.6 years) and 30 healthy controls (20 men; average age 52.0 ± 13.2 years) who have undergone late gadolinium enhancement (LGE) CMR. Next, 127 HCM patients were divided randomly into two sets including training cohort and validation cohort. Strain and imaging parameters were measured and analyzed statistically. RESULTS: Based on univariate and multivariate analysis, segmental circumferential strain (SCS) (p < 0.001) and maximal wall thickness (MWT) (p < 0.001) may differentiate myocardial segments with or without LGE as significant biomarkers for both sets. The area under the curve (AUC) was 0.803 (95% CI 0.785-0.820) for SCS and 0.777 (95% CI 0.759-0.795) for MWT to identify myocardial fibrosis. When combining SCS >-13.9% and MWT >16.4mm, the specificity of the model (AUC = 0.779; 95% CI 0.760-0.796) achieved the highest 93.9%, with a sensitivity of 61.8%. CONCLUSION: Strain analysis in HCM holds promise for myocardial fibrosis detection and SCS is the best strain parameter based on CMR. Nevertheless, the model of combining SCS and MWT could achieve the highest specificity for fibrotic diagnosis.

Applying quantitative CMR parameters for detecting myocardial lesion in immune checkpoint inhibitors-associated myocarditis.

PURPOSE: Sparse researches evaluated the quantitative cardiovascular magnetic resonance (CMR) parameters for immune checkpoint inhibitors (ICI)-associated myocarditis. We aimed to apply quantitative CMR mappings and late gadolinium enhancement (LGE) extent for detecting ICI-associated myocarditis. METHOD: The retrospective study included patients with ICI-associated myocarditis and CMR examination from August 2018 to August 2021 in our hospital. ICI-associated myocarditis was clinically diagnosed based on the clinical criteria by European Society of Cardiology guidelines. The multiparametric CMR images including T2 mapping and black blood T2-weighted images were used to evaluate myocardial edema. The myocardial edema ratio (ER) ≥ 2.0 was applied for determining myocardial edema on T2-weighted images. RESULTS: 56 patients with ICI-associated myocarditis were included. The global T2 value and native T1 value of patients with ICI-associated myocarditis were significantly higher than the reference ranges in our hospital (p < 0.05). The rate of elevated global T2 value (92%) was significantly higher than those of abnormal native T1 value (73%), ER (52%) and LGE presence (68%) in patients with ICI-associated myocarditis (p < 0.05). The LGE extent and left ventricular ejection fraction of patients with ICI-associated myocarditis were 10.38 ± 9.64% and 56.42 ± 8.54%, respectively. LGE extent inversely correlated with left ventricular ejection fraction (r = -0.38, p = 0.004) but positively correlated with native T1 value (r = 0.28, p < 0.04) and extracellular volume (r = 0.50, p = 0.001). CONCLUSIONS: T2 mapping could detect higher rate of patients with ICI-associated myocarditis than native T1 mapping, ER and LGE presence. LGE extent inversely correlated with left ventricular ejection fraction but positively correlated with native T1 value and extracellular volume in patients with ICI-associated myocarditis.

Role of collateral flow in infarct border zone extent and contractile function in patients with chronic coronary total occlusion.

PURPOSE: There is a paucity of data regarding the border zone parameters in patients with chronic coronary total occlusion (CTO). We investigated the border zone extent and contractile function and their associations with collateral flow. METHODS: CTO patients (n = 47) and sex- and age-matched volunteers (n = 15) were prospectively enrolled and underwent cardiac MRI examinations to acquire cine and late-gadolinium enhancement (LGE) images. Myocardial peak strain (PS) and the time to PS were determined at the segmental level and global level. Infarct, border zone, adjacent, and remote regions were defined according to the transmural extent of infarction (TEI) by LGE at each segment. Angiographic collateral flow was evaluated using the Rentrop grading system. RESULTS: CTO patients with well-developed collateral flow had a higher TEI in border zone regions compared to patients with poorly developed collateral flow (p = 0.02). Conversely, CTO patients with poorly developed collaterals showed a higher TEI in infarct regions (p < 0.01). Enhanced border function, characterized by greater PS and earlier time to PS, was noted in well-developed collaterals (all p < 0.05). In the multivariate linear analyses, the level of collateral flow was an independent predictor of the border zone extent (ß = 0.40, p = 0.02) and contractile function (radial: ß = -0.42, p = 0.02; circumferential: ß = 0.39, p = 0.02; and longitudinal: ß = 0.47, p < 0.01). CONCLUSIONS: In CTO patients, the presence of well-developed collateral flow was closely linked to a greater extent of LGE and contractile function in border zone regions. Our findings shed light on the cardiac MRI-based pathophysiological underpinning in border zone regions, which could offer complementary and prognostic information in clinical practice.

A randomized multicenter trial to evaluate early invasive strategy for patients with acute ST-segment elevation myocardial infarction presenting 24-48 hours from symptom onset: Protocol of the RESCUE-MI study.

BACKGROUND: For ST-segment elevation myocardial infarction (STEMI) patients presenting 24 to 48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial. METHODS: This is a prospective, open-label, multicenter, investigator initiated, randomized controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed). All patients will be followed for 1 month. The primary end point is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary end points are as follows: (1) major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; (2) other CMR end points, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume. DISCUSSION: This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset and will add more evidence for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04962178. Registered on July 14, 2021.

How can the rate of nontherapeutic thymectomy be reduced?

OBJECTIVES: The aim of this study was to determine the prevalence of nontherapeutic thymectomy and define a clinical standard to reduce it. METHODS: From 2016 to 2020, consecutive patients who underwent thymectomy were retrospectively reviewed. Univariable and multivariable analyses were used to identify the correlation factors of nontherapeutic thymectomy. A receiver operating characteristic curve was analysed to assess the cut-off threshold of factors correlated with nontherapeutic thymectomy. RESULTS: A total of 1039 patients were included in this study. Overall, 78.4% (n = 814) of thymectomies were therapeutic and 21.6% (n = 225) were nontherapeutic. Thymoma (57.9%, n = 602) was the most common diagnosis in therapeutic thymectomy. Among those of nontherapeutic thymectomy, thymic cysts (11.9%, n = 124) were the most common lesion. Compared with therapeutic thymectomy, patients with nontherapeutic thymectomy were more likely to be younger (median age 50.1 vs 55.6 years, P < 0.001) with a smaller precontrast and postcontrast computed tomography (CT) value (P < 0.001, P < 0.001), as well as ΔCT value [10.7 vs 23.5 Hounsfield units (HU), P < 0.001]. Multivariable analysis indicated that only age and ΔCT value were significantly different between therapeutic and nontherapeutic thymectomy groups. Receiver operating characteristic curve analysis showed that cut-off values of age and ΔCT value were 44 years and 6 HU, respectively. Patients with age ≤44 years and a ΔCT value ≤6 HU had a 95% probability of nontherapeutic thymectomy. CONCLUSIONS: Surgeons should be cautious to perform thymectomy for patients with age ≤44 years and ΔCT value ≤6 HU. This simple clinical standard is helpful to reduce the rate of nontherapeutic thymectomy.

The prognostic value of global myocardium strain by CMR-feature tracking in immune checkpoint inhibitor-associated myocarditis.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. METHODS: In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). CONCLUSIONS: GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. KEY POINTS: • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

Unenhanced Whole-Heart Coronary MRA: Prospective Intraindividual Comparison of 1.5-T SSFP and 3-T Dixon Water-Fat Separation GRE Methods Using Coronary Angiography as Reference.

BACKGROUND. Coronary MRA is commonly performed at 1.5 T using SSFP acquisitions. Coronary MRA performed at 3 T using SSFP is limited due to impaired fat suppression and has been typically investigated using contrast-enhanced techniques. A Dixon fat-water separation gradient-recalled echo (GRE) method may enable high-quality unenhanced 3-T coronary MRA. OBJECTIVE. The purpose of this study was to compare 1.5-T SSFP and 3-T Dixon water-fat separation GRE methods for unenhanced whole-heart coronary MRA in patients with suspected coronary artery disease (CAD). METHODS. This prospective study included 44 patients (27 men and 17 women; mean age, 59 ± 8 [SD] years) with an intermediate to high risk of CAD who underwent both 1.5-T SSFP and 3-T Dixon GRE coronary MRA examinations before undergoing coronary angiography (CAG). Two radiologists independently assessed coronary arteries in terms of subjective image quality (on a scale of 1-5, with 5 denoting the highest image quality), number of visible segments, apparent contrast-to-noise ratio (CNR; vs myocardium), and presence of significant stenoses. Methods were compared using the mean of the readers' values for apparent CNR and using consensus interpretations for other measures. CAG served as the reference standard for detecting the presence of stenoses. RESULTS. Expressed as a kappa coefficient, interobserver agreement was 0.85 for image quality, 0.85 for segment visibility, and 0.83 for stenosis, and expressed as an intraclass correlation coefficient, interobserver agreement was 0.92 for apparent CNR. The mean overall image quality score was 4.0 ± 1.1 for 3-T Dixon GRE versus 3.0 ± 1.2 for 1.5-T SSFP. The percentage of visible segments for 3-T Dixon GRE versus 1.5-T SSFP was 96.7% versus 88.9% for all segments, 96.9% versus 90.1% for distal segments, and 93.1% versus 77.2% for branch segments. The mean overall apparent CNR was 93.2 ± 29.2 for 3-T Dixon GRE versus 80.8 ± 27.9 for 1.5-T SSFP. The 3-T Dixon GRE method, compared with the 1.5-T SSFP method, showed higher sensitivity and specificity in per-vessel analysis (87.9% vs 77.3% and 83.3% vs 60.6%, respectively), per-segment analysis (84.6% vs 74.8% and 90.9% vs 79.6%, respectively), and per-segment analysis of distal and branch segments (89.7% vs 75.9% and 89.7% vs 73.7%, respectively). CONCLUSION. For unenhanced coronary MRA, 3-T unenhanced Dixon GRE had better image quality and diagnostic performance than 1.5-T SSFP, particularly for distal and branch segments. CLINICAL IMPACT. The 3-T Dixon GRE technique may be preferred to the current clinical standard of the 1.5-T SSFP technique for unenhanced coronary MRA.

Clinical Application of Non-Contrast-Enhanced Dixon Water-Fat Separation Compressed SENSE Whole-Heart Coronary MR Angiography at 3.0 T With and Without Nitroglycerin.

BACKGROUND: 3.0 T non-contrast-enhanced nitroglycerin (NTG)-assisted whole-heart coronary magnetic resonance angiography (MRA) employing Dixon water-fat separation and compressed SENSE (CS-SENSE) acceleration is a promising method for diagnosing coronary artery disease (CAD). PURPOSE: To evaluate the diagnostic performance of this technique for detecting clinically-relevant (≥50% diameter reducing) CAD and to evaluate the difference in NTG-induced coronary vasodilation between patients with and without clinically-relevant CAD. STUDY TYPE: Prospective. POPULATION: Sixty-six patients with suspected CAD. FIELD STRENGTH/SEQUENCE: 3.0 T; CSSENSE, Dixon water-fat separation, three-dimensional segmented turbo field gradient-echo sequence for whole-heart coronary MRA. ASSESSMENT: Overall image quality of coronary MRA was calculated on the basis of all visible coronary segments. The diagnostic performance of coronary MRA for detecting a ≥50% reduction in coronary artery diameter with and without NTG was compared using X-ray coronary angiography (CAG) as the reference. According to CAG, patients were divided into a non-clinically-relevant CAD group and clinically-relevant CAD group, and the difference in NTG-induced vasodilation between the groups was evaluated. STATISTICAL TESTS: Unpaired/paired Student's t-test, Mann-Whitney U test, paired Wilcoxon signed-rank test, χ2 test, McNemar test. A two-tailed P value <0.05 was considered significant. RESULTS: Overall image quality was increased significantly in the coronary MRA images after NTG. The diagnostic performance of the non-NTG vs. NTG-assisted coronary MRA was as follows on a per-patient basis: sensitivity 94.3% vs. 94.3%, specificity 64.5% vs. 83.9%, positive predictive value 75.0% vs. 86.8%, negative predictive value 90.9% vs. 92.9%, and accuracy 80.3% vs. 89.4%, respectively. NTG-induced vasodilation was significantly lower in the clinically-relevant CAD group than in the non-clinically-relevant CAD group (13.7 ± 8.1% vs. 24.1 ± 16.3%). DATA CONCLUSION: Non-contrast Dixon water-fat separation CS-SENSE coronary MRA at 3.0 T can noninvasively detect clinically-relevant CAD and sublingual NTG improved performance. Combining pre- and post-NTG coronary MRA may provide a simple noninvasive and nonionizing test to evaluate coronary vasodilation function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Assessment of Non-contrast-enhanced Dixon Water-fat Separation Compressed Sensing Whole-heart Coronary MR Angiography at 3.0 T: A Single-center Experience.

RATIONALE AND OBJECTIVES: The clinical utility of Dixon water-fat separation coronary MR angiography (CMRA) with compressed sensing (CS) reconstruction has not been determined in a patient population. This study was designed to evaluate the performance of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA sequence in vitro and in vivo. MATERIALS AND METHODS: In vitro phantom MRI, we compared key parameters of the SENSE and CS images. And in this prospective in vivo study, from November 2019 to October 2020, 94 participants were recruited for 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography (CA) as the reference method. RESULTS: Compared with SENSE, CS with an appropriate acceleration factor offers both higher SNR/CNR (p < 0.05) and a shortened acquisition. Fifty-eight patients successfully completed the CMRA and CA. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA according to a patient-based analysis were 96.4%, 66.7%, 73.0%, 95.2% and 81.0%, respectively. The area under the receiver-operator characteristic (ROC) curve (AUC) of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA for detecting significant coronary artery stenosis is 0.908, 0.895, and 0.904 in patient-, vessel-, and segment-based analyses respectively. CONCLUSION: 3.0 T non-contrast-enhanced Dixon water-fat separation whole-heart CMRA using appropriate CS is a promising noninvasive and radiation-free technique to detect clinically significant coronary stenosis on patients with suspected CAD.

Nivolumab-associated DRESS in a genetic susceptible individual.

The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B+ and perforin+ CD8+ T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related 'off-target effect' and PD-1 block-mediated 'on-target effect'. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS.

Role of free-breathing motion-corrected late gadolinium enhancement technique for image quality assessment and LGE quantification.

OBJECTIVE: To compare the image quality and late gadolinium enhancement (LGE) quantification between free-breathing motion-corrected and conventional breath-hold LGE method in a variety of cardiovascular diseases. MATERIALS AND METHODS: 149 consecutive patients underwent contrast-enhanced cardiac magnetic resonance examination employing both free-breathing motion-corrected LGE and conventional breath-hold LGE method. Scan time, contrast-to-noise ratio, overall image quality score and LGE mass were measured and analyzed statistically. RESULTS: Free-breathing motion-corrected LGE method had a shorter scan time and higher overall image quality score in comparison with conventional breath-hold LGE method (p < 0.001). Univariate/multivariate logistic regression analysis showed that breath-holding difficulty, high heart rate and arrhythmia could be predictive factors possibly for an inferior image quality score (p < 0.05 for all). The contrast-to-noise ratios of free-breathing motion-corrected LGE images were higher than those of conventional breath-hold LGE images (p < 0.001). In the cases with subepicardial and/or transmural myocardial enhancement, the measured LGE masses were larger on free-breathing motion-corrected LGE images in comparison with those on conventional breath-hold LGE images (p < 0.05). CONCLUSION: Free-breathing motion-corrected LGE could be a better choice for patients who need contrast-enhanced cardiac MRI and have one or more of the risk factors for an inferior image quality score, including breath-holding difficulty, high heart rate and arrhythmia. However, an overestimation of LGE mass on free-breathing motion-corrected LGE image should be taken into consideration when LGE pattern involves subepicardial and/or transmural myocardium.

Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: The Utility of Myocardial Strain Based on Cardiac MR Tissue Tracking.

BACKGROUND: Myocardial strain for assessment of hypertrophic cardiomyopathy (HCM) is of importance and may play a role in identifying obstruction in HCM patients. PURPOSE: To evaluate the utility of myocardial strain for detecting left ventricular (LV) outflow tract (LVOT) obstruction in HCM patients based on magnetic resonance tissue tracking. STUDY TYPE: Retrospective. POPULATION: In all, 44 adult HCM patients with LVOT obstruction and 108 adult HCM patients without LVOT obstruction. FIELD STRENGTH/SEQUENCE: 1.5 T; Steady-state free-precession cine sequence; phase-sensitive inversion-prepared segmented gradient echo sequence for late gadolinium enhancement (LGE) imaging. ASSESSMENT: Strain parameters including the local and global levels of LV myocardium and the subtraction (Sub) of myocardial strain variables between interventricular septal segments (IVSS) and noninterventricular septal segments (NIVSS) were measured for differentiating HCM with obstruction from nonobstruction. Average and maximum LV wall thickness (Average and Maximum LVWT) were also analyzed. STATISTICAL TESTS: Univariate and multivariate logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), intraclass correlation coefficient. RESULTS: In multivariate analysis, Average LVWT, Maximum LVWT, and the subtraction of radial peak strain (Sub Radial PS) between NIVSS and IVSS were independently associated with LVOT obstruction. The AUCs were 0.731, 0.840, and 0.890 for Average LVWT, Maximum LVWT, and Sub Radial PS, respectively. Sub Radial PS (cutoff value: 8.1%) demonstrated the highest sensitivity of 75.0% and a high specificity of 87.9% for identifying LVOT; Maximum LVWT (cutoff value: 22.9 mm) showed good sensitivity (72.7%) and specificity (83.3%). Combining Maximum LVWT >22.9 mm and Sub Radial PS > 8.1% achieved a better diagnostic performance (specificity 95.4%, sensitivity 70.5%). DATA CONCLUSION: Combining Maximum LVWT >22.9 mm and Sub Radial PS >8.1% holds promise for objectively evaluating LVOT obstruction in HCM patients with very high specificity and acceptable sensitivity. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Clinical significance of PET/CT uptake for peripheral clinical N0 non-small cell lung cancer.

OBJECTIVE: In this cohort study, we determined the clinical value of the maximum standardized uptake value (SUVmax) of primary tumors in non-small cell lung cancer (NSCLC). STUDY DESIGN: A retrospective review of NSCLC patients was performed from January 2011 to December 2017. Peripheral cN0 NSCLC patients with tumor size ≤2 cm were included. SUVmax was calculated as a continuous variable for semiquantitative analyses. A receiver operating characteristic curve was analyzed to assess the cutoff threshold of SUVmax on pathological (p) nodal metastasis. We further evaluated the clinical relevance of SUVmax in peripheral cN0 NSCLC patients. RESULTS: A total of 670 peripheral NSCLC patients with tumor size ≤2 cm were deemed cN0 by preoperative PET/CT scan. Statistical analyses suggested significant correlations of SUVmax with smoking status (P = .026), tumor volume (P = .001), pathology type (P = .008), tumor differentiation (P < .001), vessel invasion (P = .001), plural invasion (P < .001), pT stage (P < .001), nodal involvement (P < .001), and pathological tumor node metastasis stage (P < .001). A cutoff point of SUVmax of 3.8 (P < .001) could be used to predict pathological nodal metastasis. Multivariable analyses indicated that preoperative SUVmax >3.8 (odds ratio, 12.149; P < .001) was an independent predictor of nodal metastasis. Overall survival analyses further suggested that SUVmax was an independent prognostic indicator (hazard ratio, 2.050; P = .017). CONCLUSION: Preoperative SUVmax is a predictor of pathological nodal metastasis and prognosis for peripheral cN0 NSCLC patients with tumor size ≤2 cm. Our results indicate that assessment of PET SUVmax could improve stratification of these patients.