Empagliflozin and left atrial function in patients with type 2 diabetes mellitus and coronary artery disease: insight from the EMPA-HEART CardioLink-6 randomized clinical trial.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. OBJECTIVE: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. METHODS: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. RESULTS: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m2, minimum LA volume 11.1 ± 5.7mL/m2) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m2, minimum LA volume 12.6 ± 5.0mL/m2) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m2 (95% CI: -1.7 to 3.7 mL/m2; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m2 (95% CI: -0.9 to 2.6 mL/m2; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference - 0.01 (95% CI: -0.05 to 0.03, p = 0.59). CONCLUSION: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970).

Cardiac magnetic resonance biomarkers as surrogate endpoints in cardiovascular trials for myocardial diseases.

Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature to precisely monitor disease activity lends itself to quantify response to novel therapeutics. This review critically appraises the value of cardiac magnetic resonance imaging biomarkers as surrogate endpoints for prospective clinical trials. The primary focus is to comprehensively outline the value of established cardiac magnetic resonance parameters in myocardial diseases. These include heart failure, cardiac amyloidosis, iron overload cardiomyopathy, hypertrophic cardiomyopathy, cardio-oncology, and inflammatory cardiomyopathies like myocarditis and sarcoidosis.

Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease.

BACKGROUND: Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. METHODS: We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. RESULTS: CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. CONCLUSIONS: Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.

Optimization of Ultrasonic-Assisted Extraction of Total Flavonoids from Abrus Cantoniensis (Abriherba) by Response Surface Methodology and Evaluation of Its Anti-Inflammatory Effect.

Abrus cantoniensis is a Chinese herbal medicine with efficacy in clearing heat and detoxification, as well as relieving liver pain. The whole plant, except the seeds, can be used and consumed. Flavonoids have been found in modern pharmacological studies to have important biological activities, such as anti-inflammatory, antibacterial and antioxidant properties. The antibacterial and antioxidant bioactivities of the total flavonoids of Abrus cantoniensis (ATF) have been widely reported in national and international journals, but there are fewer studies on their anti-inflammatory effects. The present study focused on the optimization of the ultrasonic extraction process of ATF by response surface methodology and the study of its anti-inflammatory effects in vitro and in vivo. The results showed that the factors that had a great impact on the ATF extraction were the material-to-liquid ratio, ultrasonic extraction cycles and ethanol concentration. The best extraction process used a material-to-liquid ratio of 1:47, ultrasonic extraction cycles of 4 times, an ethanol concentration of 50%, an ultrasonic extraction time of 40 min and an ultrasonic power of 125 W. Under these conditions, the actual extraction rate of total flavonoids was 3.68%, which was not significantly different from the predicted value of 3.71%. In an in vitro anti-inflammatory assay, ATF was found to be effective in alleviating LPS (lipopolysaccharide)-induced inflammation in mouse peritoneal macrophages. In an in vivo anti-inflammatory assay, ATF was found to have a significant inhibitory effect on xylene-induced ear swelling in mice and cotton ball granuloma in mice, and the inhibitory effect was close to that of the positive control drug dexamethasone. This may provide a theoretical basis for the further development of the medicinal value of Abrus cantoniensis.

Appropriateness of inpatient stress testing: Implications for development of clinical decision support mechanisms and future criteria.

BACKGROUND: An upcoming national mandate will require consultation of appropriate use criteria (AUC) through a clinical decision support mechanism (CDSM) for advanced imaging. We aimed to evaluate our current ability to ascertain test appropriateness. METHODS: We prospectively collected data on 288 consecutive stress tests and coronary computed tomography angiography studies for medical inpatients. Study appropriateness was determined independently by two physicians using the 2013 Multimodality AUC. RESULTS: The median age of the study population was 66 years [interquartile range (IQR) 56, 75], 40.8% were female, and 52.8% had a history of coronary artery disease. Review of the electronic health record (EHR) alone was sufficient to deem appropriateness for 87.2% of cases. The most common reason it was insufficient was inability to determine if the patient could exercise (59.5%). After reviewing the EHR and pilot CDSM data together, appropriateness could be determined for 95.8% of the cases. The most common reason appropriateness could not be determined was that the exam indication was not addressed by an AUC criterion (83.3%). CONCLUSION: In preparing for the mandate, it will be important for future CDSM to obtain information on the patient's ability to exercise and for future AUC to include additional indications that are not currently addressed.

Stress cardiac MRI in stable coronary artery disease.

PURPOSE OF REVIEW: Non-invasive testing is often the first step in the evaluation of stable coronary artery disease (CAD). Stress cardiac magnetic resonance imaging (CMR) is an established modality with high diagnostic accuracy and prognostic value. This review will focus on the recent advances in understanding how stress CMR can help guide patient care. RECENT FINDINGS: Diagnostic accuracy of stress CMR has been validated against coronary angiography with fractional flow reserve (FFR) in patients with stable CAD. Large registry data have shown stress CMR to have important prognostic importance and that its cost-effectiveness compares favorably to alternatives. In patients with stable CAD, guidance using a CMR based strategy led to equivalent outcomes when compared to coronary angiography with FFR. SUMMARY: In persons with stable CAD, Stress CMR is an accurate and cost-effective imaging modality that should be considered in patients at intermediate pre-test probability of CAD. Prognostic studies have shown it to have excellent negative predictive value and that it can safely serve as a "gatekeeper" for invasive angiography.

MRI in Patients with Cardiac Implantable Electronic Devices.

Indications for MRI have grown considerably in recent years. However, many patients with cardiac implantable electronic devices are denied imaging due to physician misinterpretation of the risks associated with MRI. This review discusses the theoretical basis for the perceived risk by exploring preclinical literature. It then presents a detailed examination of the true rates of adverse events in clinical studies across both MR nonconditional (legacy) and MR conditional devices. Indeed, many of these adverse events are rare, nonexistent, and/or clinically insignificant in the wealth of published data. The authors then address image quality and the constituents of a safety checklist that institutions should consider when performing MRI in patients with a cardiac implantable electronic device. Lastly, the authors conclude with an overview of future directions for advancement in the field.

Peptide Bond Synthesis by a Mechanism Involving an Enzymatic Reaction and a Subsequent Chemical Reaction.

We recently reported that an amide bond is unexpectedly formed by an acyl-CoA synthetase (which catalyzes the formation of a carbon-sulfur bond) when a suitable acid and l-cysteine are used as substrates. DltA, which is homologous to the adenylation domain of nonribosomal peptide synthetase, belongs to the same superfamily of adenylate-forming enzymes, which includes many kinds of enzymes, including the acyl-CoA synthetases. Here, we demonstrate that DltA synthesizes not only N-(d-alanyl)-l-cysteine (a dipeptide) but also various oligopeptides. We propose that this enzyme catalyzes peptide synthesis by the following unprecedented mechanism: (i) the formation of S-acyl-l-cysteine as an intermediate via its "enzymatic activity" and (ii) subsequent "chemical" S → N acyl transfer in the intermediate, resulting in peptide formation. Step ii is identical to the corresponding reaction in native chemical ligation, a method of chemical peptide synthesis, whereas step i is not. To the best of our knowledge, our discovery of this peptide synthesis mechanism involving an enzymatic reaction and a subsequent chemical reaction is the first such one to be reported. This new process yields peptides without the use of a thioesterified fragment, which is required in native chemical ligation. Together with these findings, the same mechanism-dependent formation of N-acyl compounds by other members of the above-mentioned superfamily demonstrated that all members most likely form peptide/amide compounds by using this novel mechanism. Each member enzyme acts on a specific substrate; thus, not only the corresponding peptides but also new types of amide compounds can be formed.

Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors.

Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation. In the present study, we examined the clinical and genetic characteristics associated with circulating CD34(+) cell frequency in a large, community-based sample of 1786 Framingham Heart Study participants.Among subjects without cardiovascular disease (n = 1595), CD34(+) frequency was inversely related to older age, female sex, and smoking. CD34(+) frequency was positively related to weight, serum total cholesterol, and statin therapy. Clinical covariates accounted for 6.3% of CD34(+) variability. CD34(+) frequency was highly heritable (h(2) = 54%; P < .0001). Genome-wide association analysis of CD34(+) frequency identified suggestive associations at several loci, including OR4C12 (chromosome 11; P = 6.7 × 10(-7)) and ENO1 and RERE (chromosome 1; P = 8.8 × 10(-7)). CD34(+) cell frequency is reduced in older subjects and is influenced by environmental factors including smoking and statin use. CD34(+) frequency is highly heritable. The results of the present study have implications for therapies that use CD34(+) cell populations and support efforts to better understand the genetic mechanisms that underlie CD34(+) frequency.

[DUOX2 mutations in children with congenital hypothyroidism].

OBJECTIVE: To study the features of DUOX2 mutations and genotype-phenotype relationship in children with congenital hypothyroidism (CH), in order to provide evidence for gene diagnosis and gene treatment of CH. METHODS: Blood samples were collected from 10 CH children with thyromegaly. Genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and direct sequencing. RESULTS: G3632A mutation in the exon 28 of DUOX2 that may result in arginine to histidine substitution at codon 1211 was found in one patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to arginine substitution at codon 678 was found in three patients. They were all heterozygous mutations. CONCLUSIONS: Heterozygous mutations in DUOX2 may affect protein function and cause CH. The relationship between DUOX2 genotypes and clinical phenotypes is unclear and needs further studies.

Downregulation of KDR expression induces apoptosis in breast cancer cells.

Angiogenesis plays a crucial role in the growth, invasion and metastasis of breast cancer. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are the key regulators of tumor angiogenesis. VEGFR-2, known as the kinase insert domain receptor (KDR), is a key receptor involved in malignant angiogenesis. We previously showed that knocking down KDR with short interference RNA (KDR-siRNA) markedly decreased KDR expression and suppressed tumor growth in a xenograft model. However, the mechanisms underlying the anti-cancer effects of KDR-siRNA are not clearly understood. This study aimed to elucidate the molecular mechanisms that induce apoptosis in human breast cancer MCF-7 cells after transfection with KDR-siRNA. We studied the effects of KDR-siRNA on proliferation, apoptosis, antiapoptotic and pro-apoptotic proteins, mitochondrial membrane permeability, cytochrome c release and caspase-3 activity. The results indicated that KDR-siRNA treatment significantly inhibited the proliferation and induced the apoptosis of MCF-7 cells, reduced the levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xl, and increased the level of the pro-apoptotic protein Bax, resulting in a decreased Bcl-2/Bax ratio. KDR-siRNA also enhanced the mitochondrial membrane permeability, induced cytochrome c release from the mitochondria, upregulated apoptotic protease-activating factor-1 (Apaf-1), cleaved caspase-3, and increased caspase-3 activity in MCF-7 cells. Furthermore, KDR-siRNA-induced apoptosis in MCF-7 cells was blocked by the caspase inhibitor Z-VAD-FMK, suggesting a role of caspase activation in the induction of apoptosis. These results indicate that the Bcl-2 family proteins and caspase-related mitochondrial pathways are primarily involved in KDR-siRNAinduced apoptosis in MCF-7 cells and that KDR might be a potential therapeutic target for human breast cancer treatments.

Determination of Antioxidant, Cytotoxicity, and Anti-human Lung Cancer Properties of Silver Nanoparticles Green-Formulated by Foeniculum vulgare Extract Combined with Radiotherapy.

The current investigation involved the silver nanoparticles green synthesis utilizing the aqueous extract derived from the Foeniculum vulgare leaves (AgNPs@FV). The effectiveness of these newly developed nanoparticles in conjunction with radiotherapy was evaluated on lung cancer cells. The synthesized AgNPs@FV underwent characterization through various analytical techniques such as energy dispersive X-ray (EDX), field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and ultraviolet-visible (UV-Vis) spectrophotometry. The efficacy of AgNPs@FV in conjunction with radiotherapy against human lung cancer was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The AgNPs@FV exhibited a spherical morphology ranging in size from 10.16 to 42.74 nm. The EDX diagram of nanoparticles shows energy signals at 3.02 and 2.64 keV, which are attributed to Ag Lß and Ag Lα, respectively. During the antioxidant evaluation, AgNPs@FV and butylated hydroxytoluene (BHT) displayed IC50 values of 166 and 59 µg/mL, respectively. The cells treated with AgNPs@FV in conjunction with radiotherapy were evaluated using the MTT assay over 48 h to determine cytotoxicity and anti-human lung cancer characteristics on normal (human umbilical vein endothelial cell (HUVEC)) and lung cancer cells and exhibited IC50 values of 211, 166, and 296 µg/mL against NCI-H2126, NCI-H1299, and NCI-H1437, respectively. Furthermore, the malignant lung cell viability decreased when treated with a combination of AgNPs@FV and radiotherapy. Based on the aforementioned findings, it is possible that the newly developed AgNPs@FV could serve as a novel chemotherapeutic medication or adjunct for addressing lung cancer following the completion of clinical trials involving human subjects.

Cardiac Magnetic Resonance Evaluation of LV Remodeling Post-Myocardial Infarction: Prognosis, Monitoring and Trial Endpoints.

Adverse left ventricular remodeling (ALVR) and subsequent heart failure after myocardial infarction (MI) remain a major cause of patient morbidity and mortality worldwide. Overt inflammation has been identified as the common pathway underlying myocardial fibrosis and development of ALVR post-MI. With its ability to simultaneously provide information about cardiac structure, function, perfusion, and tissue characteristics, cardiac magnetic resonance (CMR) is well poised to inform prognosis and guide early surveillance and therapeutics in high-risk cohorts. Further, established and evolving CMR-derived biomarkers may serve as clinical endpoints in prospective trials evaluating the efficacy of novel anti-inflammatory and antifibrotic therapies. This review provides an overview of post-MI ALVR and illustrates how CMR may help clinical adoption of novel therapies via mechanistic or prognostic imaging markers.

Head-to-Head Comparison and Temporal Trends of Cardiac MRI Recommendations in ESC versus ACC/AHA Guidelines: A Systematic Review and Meta-Analysis.

Purpose To provide a comprehensive head-to-head comparison and temporal analysis of cardiac MRI indications between the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines to identify areas of consensus and divergence. Materials and Methods A systematic review and meta-analysis was conducted. ESC and ACC/AHA guidelines published until May 2023 were systematically screened for recommendations related to cardiac MRI. The class of recommendation (COR) and level of evidence (LOE) for cardiac MRI recommendations were compared between the two guidelines and between newer versus older versions of each guideline using χ2 or Fisher exact tests. Results ESC guidelines included 109 recommendations regarding cardiac MRI, and ACC/AHA guidelines included 90 recommendations. The proportion of COR I and LOE B was higher in ACC/AHA versus ESC guidelines (60% [54 of 90] vs 46.8% [51 of 109]; P = .06 and 53% [48 of 90] vs 35.8% [39 of 109], respectively; P = .01). The increase in the number of cardiac MRI recommendations over time was significantly higher in ESC guidelines (from 63 to 109 for ESC vs from 65 to 90 for ACC/AHA; P = .03). The main areas of consensus were found in heart failure and hypertrophic cardiomyopathy, while the main divergences were in valvular heart disease, arrhythmias, and aortic disease. Conclusion ESC guidelines included more recommendations related to cardiac MRI use, whereas the ACC/AHA recommendations had higher COR and LOE. The number of cardiac MRI recommendations increased significantly over time in both guidelines, indicating the increasing role of cardiac MRI evaluation and management of cardiovascular disease. Keywords: Cardiovascular Magnetic Resonance, Guideline, European Society of Cardiology, ESC, American College of Cardiology/American Heart Association, ACC/AHA Supplemental material is available for this article. © RSNA, 2024.

Stress CMR Perfusion Imaging in the Medicare-Eligible Population: Insights From the SPINS Study.

BACKGROUND: Patients aged ≥65 years account for a disproportionately large portion of cardiovascular (CV) events and pose a challenge for noninvasive detection of coronary artery disease. OBJECTIVES: This study sought to determine the prognostic value of stress cardiac magnetic resonance (CMR) in a Medicare-eligible group of patients in a multicenter setting in the United States. METHODS: From a multicenter U.S. registry, the study identified patients aged ≥65 years who were referred for stress CMR for evaluation of myocardial inducible ischemia. The primary outcome was defined as CV death or nonfatal myocardial infarction, whereas the secondary outcome was defined as any primary outcome, hospitalization for unstable angina, hospitalization for congestive heart failure, and unplanned late coronary artery bypass grafting. The associations of CMR findings with CV outcomes adjusted to clinical risk markers and health care cost spending were determined. RESULTS: Among 1,780 patients (aged 73 ± 5.7 years; 46% female), study investigators observed 144 primary events and 323 secondary events, over a median follow-up of 4.8 years. The presence of inducible ischemia and late gadolinium enhancement (LGE) was associated with incrementally higher event rates. Patients with neither inducible ischemia nor LGE experienced a <1% annualized rate of primary outcome. In a multivariable model adjusted for CV risk factors, inducible ischemia and LGE maintained an independent association with primary (HR: 2.80 [95% CI: 1.93-4.05]; P < 0.001; and HR: 1.85 [95% CI: 1.21-2.82]; P = 0.004, respectively) and secondary (HR: 2.46 [95% CI: 1.90-3.19]; P < 0.001; and HR: 1.72 [95% CI: 1.30-2.27]; P < 0.001, respectively) outcomes. Rates of revascularization, as well as downstream costs for patients without CMR-detected inducible ischemia, remained low throughout the follow-up period. CONCLUSIONS: In a multicenter cohort of Medicare-eligible older patients, stress CMR was effective in providing risk stratification. (Stress CMR Perfusion Imaging in the United States [SPINS] study; NCT03192891).

Association of Adverse Clinical Outcomes With Peri-Infarct Ischemia Detected by Stress Cardiac Magnetic Imaging.

BACKGROUND: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction. OBJECTIVES: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers. METHODS: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery. RESULTS: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HRadjusted: 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%). CONCLUSIONS: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events.

Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer.

BACKGROUND: Cancer cell differentiation is an important characteristic of malignant tumor and has a great impact on prognosis and therapeutic decision for patients. The N-myc downstream regulated gene 1 (NDRG1), a putative tumor suppression gene, is involved in the regulation of human cell differentiation and metastasis in various cancers. Changes in the status of methylation of the NDRG1 gene have not been studied in detail in human breast cancer. RESULTS: The MDA-MB-231 breast tumor cell line could express NDRG1. However, it was only expressed after treatment with 5-Aza-2'-deoxycytidine (AZA) in T47D cell line, which revealed that NDRG1 expression could modulated by DNA methylation. Therefore, the fragment surrounding the transcript start site of NDRG1 gene promoter was cloned after sodium bisulfite DNA treatment. A high density (66%) of methylation for human NDRG1 gene promoter was detected in T47D; however, there was only 16% of methylated CpG dinucleotides in the NDRG1 gene promoter in MDA-MB-231. DNA methylation in the NDRG1 promoter was detected in 31.1% of primary breast cancer samples. Furthermore, the NDRG1 promoter methylation correlated with the Tumor Node Metastasis (TNM) at stage III/IV, metastasis, lymph invasion, moderate and poor histological grade in the breast cancer patients. CONCLUSION: These findings suggest that the DNA methylation status of NDRG1 gene may play an important role in the pathogenesis and/or development of breast cancer, and the expression could be regulated by aberrant DNA methylation.

Diagnostic Impact and Prognostic Value of Cardiac Magnetic Resonance in Patients With Ventricular Arrhythmias.

BACKGROUND: Cardiac magnetic resonance (CMR) characterizes myocardial substrate relevant to sudden cardiac death (SCD). However, its clinical value in patients presenting with ventricular arrhythmias is still being defined. OBJECTIVES: The authors sought to examine the diagnostic and prognostic value of multiparametric CMR in a cohort of consecutive patients referred for assessment of ventricular arrhythmias. METHODS: Consecutive patients undergoing CMR for nonsustained ventricular tachycardia (NSVT) (n = 345) or sustained ventricular tachycardia (VT)/aborted SCD (n = 297) were followed over a median of 4.4 years. Major adverse cardiac events included death, recurrent VT/ventricular fibrillation requiring therapy, and hospitalization for congestive heart failure. RESULTS: Of the 642 patients, 256 were women (40%), mean age was 54 ± 15 years, and median left ventricular ejection fraction was 58% (IQR: 49%-63%). A structurally abnormal heart by CMR assessment was detected in 40% of patients with NSVT and 66% in those with VT/SCD (P < 0.001). CMR assessment yielded a diagnostic change in 27% of NSVT patients vs 41% of those with VT/SCD (P < 0.001). During follow-up, 51 patients (15%) with NSVT and 104 patients (35%) with VT/SCD experienced major adverse cardiac events (MACE). An abnormal CMR was associated with a higher annual rate for MACE for both NSVT (0.7% vs 7.7%; P < 0.001) and VT/SCD (3.8% vs 13.3%; P < 0.001) patients. In a multivariate model including left ventricular ejection fraction, an abnormal CMR remained strongly associated with MACE in NSVT (HR: 5.23 [95% CI: 2.28-12.0]; P < 0.001) and VT/SCD (HR: 1.88 [95% CI: 1.07-3.30]; P = 0.03). Adding CMR assessment to the multivariable model for MACE yielded a significant improvement in the integrated discrimination improvement and an improvement in the C-statistic in the NSVT cohort. CONCLUSIONS: In patients presenting with ventricular arrhythmias, multiparametric CMR assessment provides diagnostic clarification and effective risk stratification beyond current standard of care.

Prognostic Value of Different Thresholds for Myocardial Scar Quantification on Cardiac MRI Late Gadolinium Enhancement Images in Patients Receiving Implantable Cardioverter Defibrillators.

Purpose: To compare the predictive value of different myocardial scar quantification thresholds using cardiac MRI for appropriate implantable cardioverter defibrillator (ICD) shock and mortality. Materials and Methods: In this retrospective, two-center observational cohort study, patients with ischemic or nonischemic cardiomyopathy underwent cardiac MRI prior to ICD implantation. Late gadolinium enhancement (LGE) was first determined visually and then quantified by blinded cardiac MRI readers using different SDs above the mean signal of normal myocardium, full-width half-maximum, and manual thresholding. The intermediate signal "gray zone" was calculated as the differences between different SDs. Results: Among 374 consecutive eligible patients (mean age, 61 years ± 13 [SD]; mean left ventricular ejection fraction, 32% ± 14; secondary prevention, 62.7%), those with LGE had a higher rate of appropriate ICD shock or death than those without (37.5% vs 26.6%, log-rank P = .04) over a median follow-up of 61 months. In multivariable analysis, none of the thresholds for quantifying scar was a significant predictor of mortality or appropriate ICD shock, while the extent of gray zone was an independent predictor (adjusted hazard ratio per 1 g = 1.025; 95% CI: 1.008, 1.043; P = .005) regardless of the presence or absence of ischemic heart disease (P interaction = .57). Model discrimination was highest for the model incorporating the gray zone (between 2 SD and 4 SD). Conclusion: Presence of LGE was associated with a higher rate of appropriate ICD shock or death. Although none of the scar quantification techniques predicted outcomes, the gray zone both in infarct and nonischemic scar was an independent predictor and may refine risk stratification.Keywords: MRI, Scar Quantification, Implantable Cardioverter Defibrillator, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2023.

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations. OBJECTIVES: In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD. METHODS: Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting. RESULTS: SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality. CONCLUSIONS: Stress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).