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Diagnostic Value of Angiography-Derived IMR for Coronary Microcirculation and Its Prognostic Implication After PCI

ABSTRACT: Background: Angiography-derived index of microcirculatory resistance (angio-IMR) is an emerging pressure-wire-free index to assess coronary microvascular function, but its diagnostic and prognostic value remains to be elucidated. Methods and Results: The study population consisted of three independent cohorts. The internal diagnostic cohort enrolled 53 patients with available hyperemic microcirculatory resistance (HMR) calculated from myocardial blood flow and pressure. The external diagnostic cohort included 35 ischemia and no obstructive coronary artery disease (INOCA) patients and 45 controls. The prognostic cohort included 138 coronary artery disease (CAD) patients who received PCI. Angio-IMR was calculated after the estimation of angiography-derived fractional flow reserve (angio-FFR) using the equation of angio-IMR = estimated hyperemic Pa × angio-FFR × [vessel length/(K × Vdiastole)]. The primary outcome was a composite of cardiac death or readmission due to heart failure at 28 months after index procedure. Angio-IMR demonstrated a moderate correlation with HMR (R = 0.74, p < 0.001) and its diagnostic accuracy, sensitivity, specificity, and area under the curve to diagnose INOCA were 79.8, 83.1, 78.0, and 0.84, respectively, with a best cut-off of 25.1. Among prognostic cohort, patients with angio-IMR ≥25.1 showed a significantly higher risk of cardiac death or readmission due to heart failure than those with an angio-IMR <25.1 (18.6 vs. 5.4%, adjusted HR 9.66, 95% CI 2.04–45.65, p = 0.004). Angio-IMR ≥25.1 was an independent predictor for cardiac death or readmission due to heart failure (HR 11.15, 95% CI 1.76–70.42, p = 0.010). Conclusions: Angio-IMR showed a moderate correlation with HMR and high accuracy to predict microcirculatory dysfunction. Angio-IMR measured after PCI predicts the risk of cardiac death or readmission due to heart failure in patients with CAD. Clinical Trial Registration: Diagnostic and Prognostic Value of Angiography-derived IMR (CHART-MiCro), NCT04825028.

SUBMITTER: Dai N

PROVIDER: S-EPMC8553988 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Circulating microRNA has recently emerged as a promising biomarker for cardiovascular disease. This study sought to evaluate the diagnostic and prognostic value of circulating miR-133a as a marker of acute myocardial infarction in acute chest pain patients undergoing coronary angiography.Plasma was collected from 312 patients with chest pain on admission in the emergency department and 67 healthy controls. MiR-133a was detected using real-time quantitative PCR and enhanced accu-TnI, creatinine kinase-MB mass, and myoglobin were measured by immunoassay. End-point events (serious adverse cardiovascular events which require hospitalization or cardiovascular death) were examined in the AMI (acute myocardical infarction) group within 1, 6, 12, and 24 months.The miR-133a level was higher in AMI patients than in non-AMI patients (P?<?0.001). In the ROC analysis, the sensitivity of miR-133a in diagnosis of AMI is 0.61 and the specificity is 0.68. In the prognostic analysis, only 1 endpoint event was observed in the non-AMI group; the amount of cases with end-point events in the AMI group at 1,6,12, and 24 months were 8, 19, 28, and 35, respectively. The cutoff value of miR-133a was determined using the median value of the AMI group and separated the patients into a positive group and a negative group. The Kaplan-Meier survival curve showed no significant difference in survival was detected in AMI patients between the miR-133a positive group and negative group after follow-up (12-month: x2?=?1.353, P?=?0.245; 24-month: x2?=?3.722, P?=?0.054). After adjusting for age, gender, Killip classes, prior myocardiac infarction history, myoglobin, LVEF (left ventricular ejection fraction), diabetes, hypertension, smoking and systolic blood pressure, miR133a had a significant association with the risk of events at 12 months (HR?=?2.869, P?=?0.024) and 24 months (HR?=?3.936, P?=?0.001).In patients undergoing coronary angiography, circulating miR-133a is upregulated in AMI patients, but it does not provide enough accuracy for clinical AMI diagnosis because it also rises in unstable angina patients. Its prognostic value in AMI is uncertain mainly for the number of cases with end-point event was small and may be further validated in a larger, better designed study.

Project description:BackgroundCoronary magnetic resonance angiography (CMRA) allows non-ionizing visualization of luminal narrowing in coronary artery disease (CAD). Although a prior study showed the usefulness of CMRA for risk stratification in short-term follow-up, the long-term prognostic value of CMRA remains unclear. The purpose of this study was to evaluate the long-term prognostic value of CMRA.MethodsA total of 506 patients without history of myocardial infarction or prior coronary artery revascularization underwent free-breathing whole-heart CMRA between 2009 and 2015. Images were acquired using a 1.5 T or 3 T scanner and visually evaluated as the consensus decisions of two observers. Obstructive CAD on CMRA was defined as luminal narrowing of ≥ 50% in at least one coronary artery. Major adverse cardiac events (MACE) comprised cardiac death, nonfatal myocardial infarction, and unstable angina.ResultsObstructive CAD on CMRA was observed in 214 patients (42%). During follow-up (median, 5.6 years), 31 MACE occurred. Kaplan-Meier curve analysis revealed a significant difference in event-free survival between patients with and without obstructive CAD for MACE (log-rank, p = 0.003) and cardiac death (p = 0.012). Annualized event rates for MACE in patients with no obstructive CAD, 1-vessel disease, 2-vessel disease, and left-main or 3-vessel disease were 0.6%, 1.5%, 2.3%, and 3.6%, respectively (log-rank, p = 0.003). Cox proportional hazard regression analysis showed that, among obstructive CAD on CMRA and clinical risk factors (age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of CAD), obstructive CAD and diabetes were significant predictors of MACE (hazard ratios, 2.9 [p = 0.005] and 2.2 [p = 0.034], respectively). In multivariate analysis, obstructive CAD remained an independent predictor (adjusted hazard ratio, 2.6 [p = 0.010]) after adjusting for diabetes. Addition of obstructive CAD to clinical risk factors significantly increased the global chi-square result from 8.3 to 13.8 (p = 0.022).ConclusionsIn long-term follow-up, free breathing whole heart CMRA allows non-invasive risk stratification for MACE and cardiac death and provides incremental prognostic value over conventional risk factors in patients without a history of myocardial infarction or prior coronary artery revascularization. The presence and severity of obstructive CAD detected by CMRA were associated with worse prognosis. Importantly, patients without obstructive CAD on CMRA displayed favorable prognosis.

Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

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Diagnostic Value of Angiography-Derived IMR for Coronary Microcirculation and Its Prognostic Implication After PCI

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