Circulating CARMN linked to six-month outcomes after acute myocardial infarction

Lower levels of cardiac mesoderm enhancer-associated non-coding RNA, or CARMN, in the blood were associated with more major adverse cardiovascular events during six months of follow-up among patients treated for acute myocardial infarction, according to a retrospective cohort study conducted in China. Researchers also found that adding serum CARMN to cardiac troponin I, creatine kinase-MB and left ventricular ejection fraction improved an exploratory model for estimating the risk of those events. The study included 156 adults with acute myocardial infarction who underwent percutaneous coronary intervention; 60 experienced a major adverse cardiovascular event and 11 were censored. Patients with lower CARMN expression had a higher observed event incidence than those with higher expression. The combined model achieved an area under the receiver operating characteristic curve of 0.867, and internal bootstrap validation produced an optimism-corrected concordance index of 0.851. These findings identify CARMN as a candidate marker for post-infarction risk assessment, but the single-center design, modest sample and lack of external validation mean the model is not ready for clinical use.

The investigators consecutively enrolled patients diagnosed with acute myocardial infarction at the Affiliated Hospital of Guangdong Medical University between January 2023 and January 2025. Eligible participants were adults admitted within 72 hours of symptom onset who met expert-consensus diagnostic criteria and had complete clinical data. People with other severe heart disease, infectious disease, malignant tumors, severe liver or kidney dysfunction, mental disorders or cognitive dysfunction that prevented cooperation were excluded. Fifty-nine healthy people who underwent physical examinations during the same period served as the control group. Venous blood was collected and echocardiography performed 24 hours after PCI. The groups did not differ significantly in age, sex, body mass index, smoking history, hypertension, diabetes or four measured lipid indicators. The myocardial infarction group did, however, have higher cTnI, CK-MB and myoglobin concentrations and a lower left ventricular ejection fraction.

CARMN was measured directly in serum by extracting RNA, reverse-transcribing it into complementary DNA and using real-time quantitative polymerase chain reaction. Expression was calculated with the 2−ΔΔCt method relative to β-actin, with the mean healthy-control value used as the calibrator. Each sample was tested in technical triplicate, and inter-assay coefficients of variation for target and reference gene cycle-threshold values were controlled below 5%. The conventional myocardial-injury measures cTnI, CK-MB and myoglobin were quantified with an automated chemiluminescence immunoassay analyzer. Echocardiography used the Simpson two-plane method to measure left ventricular volume and ejection fraction, with measurements taken across three consecutive cardiac cycles and averaged. This design allowed the investigators to test whether circulating CARMN supplied prognostic information beyond laboratory markers of myocardial injury and an echocardiographic measure of ventricular function.

In the case-control comparison, serum CARMN was significantly lower in patients with acute myocardial infarction than in healthy controls. Its receiver operating characteristic curve for distinguishing the two groups had an area under the curve of 0.849. At a reported cutoff of 0.865, sensitivity was 74.36% and specificity was 83.05%. Among patients with myocardial infarction, CARMN was inversely correlated with cTnI, with a Pearson coefficient of −0.623; with CK-MB, at −0.729; and with myoglobin, at −0.747. It was positively correlated with left ventricular ejection fraction, at 0.672. These associations show that lower circulating CARMN accompanied greater biochemical evidence of myocardial injury and lower measured systolic function in this cohort. They do not establish that CARMN causes either injury or subsequent events, and the comparison with healthy controls did not test CARMN in a prospective population of patients suspected of having an infarction.

For prognosis, the researchers divided the 156 infarction patients into two equal groups according to the median CARMN value, with 78 classified as high-expression and 78 as low-expression. Kaplan–Meier analysis showed a higher incidence of major adverse cardiovascular events in the low-expression group, with a log-rank P value below 0.001. Direct group comparisons also found significantly lower CARMN levels among the 60 patients who experienced an event than among the 96 who did not. The composite endpoint consisted of all-cause death, non-fatal myocardial infarction, non-fatal stroke, heart failure or malignant arrhythmia, with any one event meeting the study criterion. During follow-up, the reported components were five deaths, nine non-fatal myocardial infarctions, 13 non-fatal strokes, 18 cases of heart failure and 15 episodes of malignant arrhythmia. The five component counts sum to 60, although the source does not state whether individual patients could experience more than one component.

Univariable and multivariable Cox regression was used to assess whether CARMN retained an association with events after conventional clinical variables were considered. Two nested models were tested. Model A included age, diabetes, cTnI, CK-MB and ejection fraction; Model B added CARMN. In the fully adjusted model, cTnI was associated with a hazard ratio of 4.878, with a 95% confidence interval of 2.026–11.747, and CK-MB with a hazard ratio of 1.823, with a 95% confidence interval of 1.334–2.491. A one-unit increase in ejection fraction was associated with a lower hazard, with a hazard ratio of 0.910 and a 95% confidence interval of 0.868–0.954. Lower CARMN expression was also associated with a higher event hazard, with the fully adjusted model reporting a hazard ratio of 0.049 for the higher-expression category and a 95% confidence interval of 0.012–0.200. Collinearity checks for the four final predictors yielded variance inflation factors from 1.072 to 1.161, which the investigators regarded as evidence against substantial multicollinearity.

In separate receiver operating characteristic analyses for six-month event prediction, CARMN alone had an area under the curve of 0.847, with a reported cutoff of 0.785, 82.46% sensitivity and 72.73% specificity. The corresponding areas under the curve were 0.690 for cTnI, 0.806 for CK-MB and 0.794 for ejection fraction. The researchers then combined CARMN, cTnI, CK-MB and ejection fraction in a nomogram for estimating individual six-month event risk. The full model achieved an area under the curve of 0.867, with a 95% confidence interval of 0.804–0.931. After 1,000 internal bootstrap resamples, its optimism-corrected concordance index was 0.851, and calibration results were consistent with observed event probabilities. Decision-curve analysis indicated greater clinical net benefit for the combined model than for a single indicator across a range of risk thresholds. These analyses evaluate discrimination, calibration and modeled net benefit; they do not show that the nomogram improves treatment selection or patient outcomes.

The incremental analysis compared the full nomogram with a baseline model containing cTnI, CK-MB and ejection fraction but not CARMN. That conventional model had an area under the curve of 0.721, with a 95% confidence interval of 0.639–0.804, and a bootstrap-corrected concordance index of 0.618 after 1,000 resamples. Its calibration suggested acceptable overall performance but a tendency to overestimate risk in the high-risk range. At six months, adding CARMN produced an integrated discrimination improvement of 0.068, with a 95% confidence interval of 0.005–0.119 and P=0.028, and a continuous net reclassification improvement of 0.196, with a 95% confidence interval of 0.023–0.444 and P=0.024. These measures indicate improved discrimination and risk classification relative to the study’s baseline model. They do not, by themselves, demonstrate better clinical outcomes or show that using CARMN would change treatment decisions.

Several limitations constrain the findings. The investigation was retrospective, conducted at one center and limited to 156 infarction patients, with 60 events and 11 censored observations over six months. The nomogram was assessed only by internal bootstrap validation, creating a risk of overfitting, and it was not compared directly with established clinical risk scores such as GRACE or TIMI. The controls were healthy individuals rather than patients with suspected acute myocardial infarction, limiting conclusions about diagnostic performance in a real diagnostic pathway. Time from symptom onset to PCI also varied and could influence biomarker measurements. The study measured circulating CARMN and observed its associations with injury markers, ventricular function and subsequent events, but it did not investigate the molecular mechanisms that might link CARMN to those outcomes. The authors describe the combined model as hypothesis-generating and call for larger multicenter external validation and comparisons with existing risk scores before it could support individualized clinical management.

Subject of Research: Circulating CARMN as a prognostic marker after acute myocardial infarction

Article Title: Circulating CARMN for acute myocardial infarction prognosis and its incremental effect when combined with conventional biomarkers

Article References: Chen, Z., Chen, J., Zhou, J., & Yao, Z. (2026). Circulating CARMN for acute myocardial infarction prognosis and its incremental effect when combined with conventional biomarkers. Frontiers in Cardiovascular Medicine, 13, 1881009. https://doi.org/10.3389/fcvm.2026.1881009

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1881009

Keywords: CARMN, acute myocardial infarction, cardiac biomarkers, prognosis, risk prediction, MACE, cardiac troponin I, left ventricular ejection fraction, long non-coding RNA, retrospective cohort, Circulating, acute