Predicting Late Gadolinium Enhancement of Acute Myocardial Infarction in Contrast-Free Cardiac Cine MRI Using Deep Generative Learning.

BACKGROUND: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is a standard technique for diagnosing myocardial infarction (MI), which, however, poses risks due to gadolinium contrast usage. Techniques enabling MI assessment based on contrast-free CMR are desirable to overcome the limitations associated with contrast enhancement. METHODS: We introduce a novel deep generative learning method, termed cine-generated enhancement (CGE), which transforms standard contrast-free cine CMR into LGE-equivalent images for MI assessment. CGE features with multislice spatiotemporal feature extractor, enhancement contrast modulation, and sophisticated loss function. Data from 430 patients with acute MI from 3 centers were collected. After image quality control, 1525 pairs (289 patients) of center I were used for training, and 293 slices (52 patients) of the same center were reserved for internal testing. The 40 patients (401 slices) of the other 2 centers were used for external testing. The CGE robustness was further tested in 20 normal subjects in a public cine CMR data set. CGE images were compared with LGE for image quality assessment and MI quantification regarding scar size and transmurality. RESULTS: The CGE method produced images of superior quality to LGE in both internal and external data sets. There was a significant (P<0.001) correlation between CGE and LGE measurements of scar size (Pearson correlation, 0.79/0.80; intraclass correlation coefficient, 0.79/0.77) and transmurality (Pearson correlation, 0.76/0.64; intraclass correlation coefficient, 0.76/0.63) in internal/external data set. Considering all data sets, CGE demonstrated high sensitivity (91.27%) and specificity (95.83%) in detecting scars. Realistic enhancement images were obtained for the normal subjects in the public data set without false positive subjects. CONCLUSIONS: CGE achieved superior image quality to LGE and accurate scar delineation in patients with acute MI of both internal and external data sets. CGE can significantly simplify the CMR examination, reducing scan times and risks associated with gadolinium-based contrasts, which are crucial for acute patients.

Comparative mitochondrial genomics of Terniopsis yongtaiensis in Malpighiales: structural, sequential, and phylogenetic perspectives.

BACKGROUND: Terniopsis yongtaiensis, a member of the Podostemaceae family, is an aquatic flowering plant displaying remarkable adaptive traits that enable survival in submerged, turbulent habitats. Despite the progressive expansion of chloroplast genomic information within this family, mitochondrial genome sequences have yet to be reported. RESULTS: In current study, the mitochondrial genome of the T. yongtaiensis was characterized by a circular genome of 426,928 bp encoding 31 protein-coding genes (PCGs), 18 tRNAs, and 3 rRNA genes. Our comprehensive analysis focused on gene content, repeat sequences, RNA editing processes, intracellular gene transfer, phylogeny, and codon usage bias. Numerous repeat sequences were identified, including 130 simple sequence repeats, 22 tandem repeats, and 220 dispersed repeats. Phylogenetic analysis positioned T. yongtaiensis (Podostemaceae) within the Malpighiales order, showing a close relationship with the Calophyllaceae family, which was consistent with the APG IV classification. A comparative analysis with nine other Malpighiales species revealed both variable and conserved regions, providing insights into the genomic evolution within this order. Notably, the GC content of T. yongtaiensis was distinctively lower compared to other Malpighilales, primarily due to variations in non-coding regions and specific protein-coding genes, particularly the nad genes. Remarkably, the number of RNA editing sites was low (276), distributed unevenly across 27 PCGs. The dN/dS analysis showed only the ccmB gene of T. yongtaiensis was positively selected, which plays a crucial role in cytochrome c biosynthesis. Additionally, there were 13 gene-containing homologous regions between the mitochondrial and chloroplast genomes of T. yongtaiensis, suggesting the gene transfer events between these organellar genomes. CONCLUSIONS: This study assembled and annotated the first mitochondrial genome of the Podostemaceae family. The comparison results of mitochondrial gene composition, GC content, and RNA editing sites provided novel insights into the adaptive traits and genetic reprogramming of this aquatic eudicot group and offered a foundation for future research on the genomic evolution and adaptive mechanisms of Podostemaceae and related plant families in the Malpighiales order.

The association between cardiac T2*BOLD and quantitative flow ratio (QFR) in the diagnosis of stenotic coronary arteries in patients with multi-vessel coronary artery disease.

BACKGROUND: T2*BOLD is based on myocardial deoxyhemoglobin content to reflect the state of myocardial oxygenation. Quantitative flow ratio is a tool for assessing coronary blood flow based on invasive coronary angiography. PURPOSE: This study aimed to evaluate the correlation between T2*BOLD and QFR in the diagnosis of stenotic coronary arteries in patients with multi-vessel coronary artery disease. METHODS: Fifty patients with MVCAD with at least 1 significant coronary artery stenosis (diameter stenosis > 50%) and 21 healthy control subjects underwent coronary angiography combined with QFR measurements and cardiovascular magnetic resonance (CMR). QFR ≤ 0.80 was considered to indicate the presence of hemodynamic obstruction. RESULTS: Totally 60 (54%) obstructive vessels had hemodynamic change. Between stenotic coronary arteries (QFR ≤ 0.8) and normal vessels, T2*BOLD showed AUCs of 0.97, 0.69, and 0.91 for left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries and PI displayed AUCs of 0.89, 0.77 and 0.90 (all p > 0.05, except for LAD). The AUCs of T2*BOLD between stenotic coronary arteries (QFR > 0.8) and normal vessels were 0.86, 0.72, and 0.85 for LAD, LCX and RCA; while, PI showed AUCs of 0.93, 0.86, and 0.88, respectively (p > 0.05). Moreover, T2*BOLD displayed AUCs of 0.96, 0.74, and 0.91 for coronary arteries as before between coronary arteries with stenosis (QFR ≤ 0.8 and > 0.8), but the mean PI of LAD, LCX and RCA showed no significant differences between them. CONCLUSION: T2* BOLD and QFR have good correlation in diagnosing stenotic coronary arteries with hemodynamic changes in patients with stable multi-vessel CAD. T2* BOLD is superior to semi-quantitative perfusion imaging in analyzing myocardial ischemia without stress.

Single-Cell Analysis Identifies Distinct Populations of Cytotoxic CD4+ T Cells Linked to the Therapeutic Efficacy of Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma.

Background: The involvement of cytotoxic CD4+ T cells (CD4+ CTLs) and their potential role in dictating the response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC) remains an unexplored area of research. Methods: Utilizing single-cell RNA sequencing, we analyzed the immunophenotype and expression patterns of CD4+ T lymphocyte subtypes in mRCC patients, followed by preliminary validation via multi-immunofluorescent staining. In addition, we obtained a comprehensive immunotherapy dataset encompassing single-cell RNA sequencing datasets and bulk RNA-seq cohorts from the European Genome-Phenome Archive and ArrayExpress database. Utilizing the CIBERSORTx deconvolution algorithms, we derived a signature score for CD4+ CTLs from the bulk-RNA-seq datasets of the CheckMate 009/025 clinical trials. Results: Single-cell analysis of CD4+ T lymphocytes in mRCC reveals several cancer-specific states, including diverse phenotypes of regulatory T cells. Remarkably, we observe that CD4+ CTLs cells constitute a substantial proportion of all CD4+ T lymphocyte sub-clusters in mRCC patients, highlighting their potential significance in the disease. Furthermore, within mRCC patients, we identify two distinct cytotoxic states of CD4+ T cells: CD4+GZMK+ T cells, which exhibit a weaker cytotoxic potential, and CD4+GZMB+ T cells, which demonstrate robust cytotoxic activity. Both regulatory T cells and CD4+ CTLs originate from proliferating CD4+ T cells within mRCC tissues. Intriguingly, our trajectory analysis indicates that the weakly cytotoxic CD4+GZMK+ T cells differentiate from their more cytotoxic CD4+GZMB+ counterparts. In comparing patients with lower CD4+ CTLs levels to those with higher CD4+ CTLs abundance in the CheckMate 009 and 25 immunotherapy cohorts, the latter group exhibited significantly improved OS and PFS probability. Conclusion: Our study underscores the pivotal role that intratumoral CD4+ CTLs may play in bolstering anti-tumor immunity, suggesting their potential as a promising biomarker for predicting response to ICIs in patients with mRCC.

Fractal analysis of left ventricular trabeculae in heart failure with preserved ejection fraction patients with multivessel coronary artery disease.

OBJECTIVES: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). METHODS: The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. RESULTS: Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806). CONCLUSION: The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis. CRITICAL RELEVANCE STATEMENT: Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients. KEY POINTS: The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease. Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular. Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.

Epicardial adipose tissue in obesity with heart failure with preserved ejection fraction: Cardiovascular magnetic resonance biomarker study.

BACKGROUND: Obesity has become a serious public health issue, significantly elevating the risk of various complications. It is a well-established contributor to Heart failure with preserved ejection fraction (HFpEF). Evaluating HFpEF in obesity is crucial. Epicardial adipose tissue (EAT) has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets. Hence, assessing EAT is of paramount importance. Cardiovascular magnetic resonance (CMR) imaging is acknowledged as the gold standard for analyzing cardiac function and morphology. We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients. AIM: To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction [HFpEF; left ventricular (LV) ejection fraction ≥ 50%] by measuring the epicardial adipose tissue (EAT) volumes and EAT mass in obese patients. METHODS: Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF. The two groups were defined as HFpEF+ and HFpEF-. LV geometry, global systolic function, EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences. RESULTS: Forty-five patients of HFpEF- group and seventeen patients of HFpEF+ group were included. LV mass index (g/m2) of HFpEF+ group was higher than HFpEF- group (P < 0.05). In HFpEF+ group, EAT volumes, EAT volume index, EAT mass, EAT mass index and the ratio of EAT/[left atrial (LA) left-right (LR) diameter] were higher compared to HFpEF- group (P < 0.05). In multivariate analysis, Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF. CONCLUSION: EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients. It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker. Further prospective studies, are needed to validate these proof-of-concept findings.

Prognostic Value of Segmental Strain After ST-Elevation Myocardial Infarction: Insights From the EARLY Assessment of MYOcardial Tissue Characteristics by Cardiac Magnetic Resonance (EARLY-MYO-CMR) Study.

BACKGROUND: The prognostic value of left ventricular segmental strain (SS) in ST-elevation myocardial infarction (STEMI) remains unclear. HYPOTHESIS: To assess the prognostic value and application of SS. STUDY TYPE: Retrospective analysis of a prospective registry. POPULATION: Five hundred and forty-four patients after STEMI (500 in Cohort 1, 44 in Cohort 2). FIELD STRENGTH/SEQUENCE: 3 T, balanced steady-state free precession, gradient echo, and gradient echo contrast-enhanced images. ASSESSMENT: Participants underwent cardiac MR during the acute phase after STEMI. Infarct-related artery (IRA) strain was determined based on SS obtained from cine images. The primary endpoint was the composite of major adverse cardiovascular events (MACEs) after 8 years of follow-up. In Cohort 2, SS stability was assessed by MR twice within 8 days. Contrast and non-contrast risk models based on SS were established, leading to the development of an algorithm. STATISTICAL TEST: Student's t-test, Mann-Whitney U-test, Cox and logistic regression, Kaplan-Meier analysis, net reclassification index (NRI). P < 0.05 was considered significant. RESULTS: During a median follow-up of 5.2 years, 83 patients from Cohort 1 experienced a MACE. Among SS, IRA peak circumferential strain (IRA-CS) was an independent factor for MACEs (adjusted hazard ratio 1.099), providing incremental prognostic value (NRI 0.180, P = 0.10). Patients with worse IRA-CS (>-8.64%) demonstrated a heightened susceptibility to MACE. Additionally, IRA-CS was significantly associated with microvascular obstruction (MVO) (adjusted odds ratio 1.084) and infarct size (r = 0.395). IRA-CS showed comparable prognostic effectiveness to global peak circumferential strain (NRI 0.100, P = 0.39), also counterbalancing contrast and non-contrast risk models (NRI 0.205, P = 0.05). In Cohort 2, IRA-CS demonstrated stability between two time points (P = 0.10). Based on risk models incorporating IRA-CS, algorithm "HJKL" was preliminarily proposed for stratification. DATA CONCLUSIONS: IRA-CS is an important prognostic factor, and an algorithm based on it is proposed for stratification. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Turnip mosaic virus NIb weakens the function of eukaryotic translation initiation factor 6 facilitating viral infection in Nicotiana benthamiana.

Viruses rely completely on host translational machinery to produce the proteins encoded by their genes. Controlling translation initiation is important for gaining translational advantage in conflicts between the host and virus. The eukaryotic translation initiation factor 4E (eIF4E) has been reported to be hijacked by potyviruses for virus multiplication. The role of translation regulation in defence and anti-defence between plants and viruses is not well understood. We report that the transcript level of eIF6 was markedly increased in turnip mosaic virus (TuMV)-infected Nicotiana benthamiana. TuMV infection was impaired by overexpression of N. benthamiana eIF6 (NbeIF6) either transiently expressed in leaves or stably expressed in transgenic plants. Polysome profile assays showed that overexpression of NbeIF6 caused the accumulation of 40S and 60S ribosomal subunits, the reduction of polysomes, and also compromised TuMV UTR-mediated translation, indicating a defence role for upregulated NbeIF6 during TuMV infection. However, the polysome profile in TuMV-infected leaves was not identical to that in leaves overexpressing NbeIF6. Further analysis showed that TuMV NIb protein, the RNA-dependent RNA polymerase, interacted with NbeIF6 and interfered with its effect on the ribosomal subunits, suggesting that NIb might have a counterdefence role. The results propose a possible regulatory mechanism at the translation level during plant-virus interaction.

Prognostic value of left ventricular trabeculae fractal analysis in patients with dilated cardiomyopathy.

BACKGROUND: The prognostic value of left ventricular (LV) myocardial trabecular complexity on cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. This study aimed to evaluate the prognostic value of LV myocardial trabecular complexity using fractal analysis in patients with DCM. METHODS: Consecutive patients with DCM who underwent CMR between March 2017 and November 2021 at two hospitals were prospectively enrolled. The primary endpoints were defined as the combination of all-cause death and heart failure hospitalization. The events of cardiac death alone were defined as the secondary endpoints.LV trabeculae complexity was quantified by measuring the fractal dimension (FD) of the endocardial border based on fractal geometry on CMR. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to examine the association between variables and outcomes. The incremental prognostic value of FD was assessed in nested models. RESULTS: A total of 403 patients with DCM (49.31 ± 14.68 years, 69% male) were recruited. After a median follow-up of 43 months (interquartile range, 28-55 months), 87 and 24 patients reached the primary and secondary endpoints, respectively. Age, heart rate, New York Heart Association functional class >II, N-terminal pro-B-type natriuretic peptide, LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, presence of late gadolinium enhancement, global FD, LV mean apical FD, and LV maximal apical FD were univariably associated with the outcomes (all P < 0.05). After multivariate adjustment, LV maximal apical FD remained a significant independent predictor of outcome [hazard ratio = 1.179 (1.116, 1.246), P < 0.001]. The addition of LV maximal apical FD in the nested models added incremental prognostic value to other common clinical and imaging risk factors (all <0.001; C-statistic: 0.84-0.88, P < 0.001). CONCLUSION: LV maximal apical FD was an independent predictor of the adverse clinical outcomes in patients with DCM and provided incremental prognostic value over conventional clinical and imaging risk factors.

Impact of Bivalirudin on Ischemia/Reperfusion Injury in Patients with Reperfused STEMI Assessed by Cardiac Magnetic Resonance.

Thrombin is an important ischemia/reperfusion injury (IRI) mediator in patients with ST-elevation myocardial infarction (STEMI). This study examines the use of bivalirudin, a direct thrombin inhibitor, in reducing IRI in STEMI patients. STEMI patients (n = 21) were treated with bivalirudin and compared to 21 patients treated with unfractionated heparin (UFH) from the EARLY Assessment of Myocardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). Infarct size (IS) and left ventricular ejection fraction (LVEF) were comparable between the two groups at follow up. During the first cardiac magnetic resonance (CMR) scan within the first week after percutaneous coronary intervention (PCI), all patients in both the bivalirudin and UFH groups exhibited myocardial edema. However, the myocardium edema volume was significantly less in the bivalirudin group (p < 0.05). At the one-month follow-up, a smaller proportion of patients in the bivalirudin group than in the UFH group exhibited myocardial edema (4.7% vs. 33.3%, p < 0.05). At the three-month follow-up, myocardial edema had completely resolved in the bivalirudin group, while it persisted in two patients in the UFH group. The incidence and volume of microvascular obstruction (MVO) were significantly lower in the bivalirudin group during the acute phase. Additionally, the incidence of intramyocardial hemorrhage (IMH) was significantly lower in the bivalirudin group during both the acute and follow up (p < 0.05). These findings were corroborated by T2 and T1 mapping results. The study concluded that the use of bivalirudin for anticoagulation is associated with attenuated IRI in STEMI patients who receive primary PCI.

Prognostic value of right atrial strains in arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. METHODS: RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan-Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. RESULTS: After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan-Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05). CONCLUSION: RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC. CRITICAL RELEVANCE STATEMENT: We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy. KEY POINTS: • Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants. • Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events. • RA booster and reservoir strain provide incremental value to conventional parameters.

Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

Fractal Analysis of Left Ventricular Trabeculae in Patients with End-Stage Renal Disease: A Random Survival Tree Analysis.

BACKGROUND: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. PURPOSE: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). STUDY TYPE: Prospective outcome study. POPULATION: 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. FIELD STRENGTH: 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. ASSESSMENT: All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. STATISTICAL TESTS: Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. RESULTS: Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. DATA CONCLUSION: LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

3D Fractal Dimension Analysis: Prognostic Value of Right Ventricular Trabecular Complexity in Participants with Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive myocardial fibro-fatty infiltration accompanied by trabecular disarray. Traditionally, two-dimensional (2D) instead of 3D fractal dimension (FD) analysis has been used to evaluate trabecular disarray. However, the prognostic value of trabecular disorder assessed by 3D FD measurement remains unclear. PURPOSE: To investigate the prognostic value of right ventricular trabecular complexity in ACM patients using 3D FD analysis based on cardiac MR cine images. STUDY TYPE: Retrospective. POPULATION: 85 ACM patients (mean age: 45 ± 17 years, 52 male). FIELD STRENGTH/SEQUENCE: 3.0T/cine imaging, T2-short tau inversion recovery (T2-STIR), and late gadolinium enhancement (LGE). ASSESSMENT: Using cine images, RV (right ventricular) volumetric and functional parameters were obtained. RV trabecular complexity was measured with 3D fractal analysis by box-counting method to calculate 3D-FD. Cox and logistic regression models were established to evaluate the prognostic value of 3D-FD for major adverse cardiac events (MACE). STATISTICAL TESTS: Cox regression and logistic regression to explore the prognostic value of 3D-FD. C-index, time-dependent receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) to evaluate the incremental value of 3D-FD. Intraclass correlation coefficient for interobserver variability. P < 0.05 indicated statistical significance. RESULTS: 26 MACE were recorded during the 60 month follow-up (interquartile range: 48-67 months). RV 3D-FD significantly differed between ACM patients with MACE (2.67, interquartile range: 2.51 ~ 2.81) and without (2.52, interquartile range: 2.40 ~ 2.67) and was a significant independent risk factor for MACE (hazard ratio, 1.02; 95% confidence interval: 1.01, 1.04). In addition, prognostic model fitness was significantly improved after adding 3D-FD to RV global longitudinal strain, LV involvement, and 5-year risk score separately. DATA CONCLUSION: The myocardial trabecular complexity assessed through 3D FD analysis was found associated with MACE and provided incremental prognostic value beyond conventional ACM risk factors. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

A Cardiac-Targeted Nanozyme Interrupts the Inflammation-Free Radical Cycle in Myocardial Infarction.

Severe systemic inflammation following myocardial infarction (MI) is a major cause of patient mortality. MI-induced inflammation can trigger the production of free radicals, which in turn ultimately leads to increased inflammation in cardiac lesions (i.e., inflammation-free radicals cycle), resulting in heart failure and patient death. However, currently available anti-inflammatory drugs have limited efficacy due to their weak anti-inflammatory effect and poor accumulation at the cardiac site. Herein, a novel Fe-Cur@TA nanozyme is developed for targeted therapy of MI, which is generated by coordinating Fe3+ and anti-inflammatory drug curcumin (Cur) with further modification of tannic acid (TA). Such Fe-Cur@TA nanozyme exhibits excellent free radicals scavenging and anti-inflammatory properties by reducing immune cell infiltration, promoting macrophage polarization toward the M2-like phenotype, suppressing inflammatory cytokine secretion, and blocking the inflammatory free radicals cycle. Furthermore, due to the high affinity of TA for cardiac tissue, Fe-Cur@TA shows an almost tenfold greater in cardiac retention and uptake than Fe-Cur. In mouse and preclinical beagle dog MI models, Fe-Cur@TA nanozyme preserves cardiac function and reduces scar size, suggesting promising potential for clinical translation in cardiovascular disease.

Left Ventricular Vertical Run-Length Nonuniformity MRI Adds Prognostic Value to MACE in Patients with End-Stage Renal Disease.

BACKGROUND: Vertical run-length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end-stage renal disease (ESRD) remains unclear. PURPOSE: To evaluate the prognostic value of VRLN MRI in patients with ESRD. STUDY TYPE: Prospective. POPULATION: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). FIELD STRENGTH/SEQUENCE: 3.0 T/steady-state free precession sequence, modified Look-Locker imaging. ASSESSMENT: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid-ventricular short-axis slice of T1 mapping. Left ventricular (LV) mass, LV end-diastolic and end-systolic volume, as well as LV global strain cardiac parameters were measured. STATISTICAL TESTS: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all-cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life-threatening arrhythmia. Cox proportional-hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C-index was computed to examine the prognostic value of VRLN. P-value <0.05 were considered statistically significant. RESULTS: Participants were followed for a median of 26 months. VRLN, age, LV end-systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C-index of the baseline model: 0.781 vs. the model added VRLN: 0.814). DATA CONCLUSION: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Deep Learning for Discrimination of Hypertrophic Cardiomyopathy and Hypertensive Heart Disease on MRI Native T1 Maps.

BACKGROUND: Native T1 and radiomics were used for hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) differentiation previously. The current problem is that global native T1 remains modest discrimination performance and radiomics requires feature extraction beforehand. Deep learning (DL) is a promising technique in differential diagnosis. However, its feasibility for discriminating HCM and HHD has not been investigated. PURPOSE: To examine the feasibility of DL in differentiating HCM and HHD based on T1 images and compare its diagnostic performance with other methods. STUDY TYPE: Retrospective. POPULATION: 128 HCM patients (men, 75; age, 50 years ± 16) and 59 HHD patients (men, 40; age, 45 years ± 17). FIELD STRENGTH/SEQUENCE: 3.0T; Balanced steady-state free precession, phase-sensitive inversion recovery (PSIR) and multislice native T1 mapping. ASSESSMENT: Compare HCM and HHD patients baseline data. Myocardial T1 values were extracted from native T1 images. Radiomics was implemented through feature extraction and Extra Trees Classifier. The DL network is ResNet32. Different input including myocardial ring (DL-myo), myocardial ring bounding box (DL-box) and the surrounding tissue without myocardial ring (DL-nomyo) were tested. We evaluate diagnostic performance through AUC of ROC curve. STATISTICAL TESTS: Accuracy, sensitivity, specificity, ROC, and AUC were calculated. Independent t test, Mann-Whitney U-test and Chi-square test were adopted for HCM and HHD comparison. P < 0.05 was considered statistically significant. RESULTS: DL-myo, DL-box, and DL-nomyo models showed an AUC (95% confidential interval) of 0.830 (0.702-0.959), 0.766 (0.617-0.915), 0.795 (0.654-0.936) in the testing set. AUC of native T1 and radiomics were 0.545 (0.352-0.738) and 0.800 (0.655-0.944) in the testing set. DATA CONCLUSION: The DL method based on T1 mapping seems capable of discriminating HCM and HHD. Considering diagnostic performance, the DL network outperformed the native T1 method. Compared with radiomics, DL won an advantage for its high specificity and automated working mode. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Complete genome sequence of Paris polyphylla chlorotic mottle virus infecting Paris polyphylla var. yunnanensis in southwest China.

A novel virus infecting a Paris polyphylla var. yunnanensis plant, tentatively named "Paris polyphylla chlorotic mottle virus" (PpCMV), was discovered in the city of Lijiang, Yunnan Province, China. Its genome consists of 6384 nucleotides (nt), excluding the 3'-terminal poly(A) tail, and contains two open reading frames: ORF1 and ORF2. ORF1 is 6150 nt in length, encoding a large 2050-aa polyprotein with at least two conserved regions encoding a replication-associated protein and a coat protein, the latter of which is located at the 3' end of ORF1. ORF2, consisting of 1185 nt, is located within ORF1 but has a different reading frame. It encodes a 394-aa-long putative movement protein. Phylogenetic analysis based on amino acid sequences revealed that the newly discovered virus exhibited the closest relationship to Hobart betaflexivirus 1 and rhodiola betaflexivirus 1, both of which belong to the genus Capillovirus, sharing 48.8% and 36.5% amino acid sequence identity, respectively, in the structural protein. This is the first report of the complete genome sequence of PpCMV in China.