Using Advanced CT Scans and Blood Markers to Better Understand Heart Damage and Recovery After a Heart Attack

SPEctral CT and miRna In Acute Myocardial Infarction for Comprehensive Adverse Remodeling Evaluation

Acute myocardial infarction with ST-segment elevation (STEMI) remains a leading cause of morbidity and mortality worldwide. Although advances in reperfusion therapy have reduced early mortality, many patients later develop adverse ventricular remodeling (AVR), which increases the risk of heart failure and cardiovascular death. Current imaging methods, such as echocardiography and cardiac magnetic resonance (CMR), provide valuable prognostic information but have limitations in availability, cost, and their ability to predict AVR early and individually.

Spectral computed tomography (CT) is an emerging imaging technique that can characterize myocardial tissue, quantify infarct size, assess microvascular obstruction, and detect complications, with lower contrast and radiation requirements compared to conventional CT. In parallel, circulating microRNAs (miRNAs) have been identified as stable and non-invasive biomarkers that reflect key biological processes in post-infarction remodeling. Several miRNAs are linked to fibrosis, apoptosis, and ventricular remodeling, suggesting their potential to complement imaging findings in risk prediction.

This study proposes a multicenter, prospective cohort of patients with STEMI and reduced left ventricular function to evaluate whether combining spectral CT tissue characterization with serum miRNA profiling can improve early prediction of AVR. The main objective is to generate and validate a multiparametric prognostic model integrating imaging and molecular biomarkers to identify high-risk patients who may benefit from closer monitoring and tailored therapeutic strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myocardial Infarction (AMI)
• Intervention / Treatment: Procedure: Blood analysis and spectral CT study; Procedure: Blood analysis, spectral CT scan and cardiac magnetic resonance imaging (CMR) study

Detailed Description

Background and Rationale Acute myocardial infarction with ST-segment elevation (STEMI) continues to represent a major public health challenge, being one of the leading causes of morbidity and mortality worldwide. Advances in reperfusion therapy, particularly primary percutaneous coronary intervention (PCI), have substantially reduced short-term mortality rates. Nevertheless, a large proportion of patients experience adverse ventricular remodeling (AVR) during follow-up. AVR is characterized by pathological changes in left ventricular (LV) geometry, wall thinning, chamber dilation, and progressive decline in contractile function. These changes are strongly associated with the development of heart failure and increased long-term mortality.

Traditional imaging modalities, such as echocardiography and cardiac magnetic resonance (CMR), have been used to characterize post-infarction myocardial damage and to monitor remodeling. Echocardiography is widely available and provides important functional information, but it lacks the ability to characterize myocardial tissue in depth. CMR is currently the gold standard for infarct size quantification, detection of microvascular obstruction, and assessment of myocardial viability; however, it is costly, time-consuming, and not universally accessible. There remains an unmet need for more accessible, rapid, and accurate tools to predict AVR early after STEMI.

Spectral computed tomography (CT) has recently emerged as an innovative imaging technique that goes beyond conventional CT by providing spectral information and material decomposition. This technology enables enhanced tissue characterization, accurate quantification of myocardial perfusion defects, and identification of complications such as myocardial rupture or thrombus, all while using reduced contrast volume and lower radiation doses compared with older-generation scanners. Preliminary data suggest that spectral CT can approximate some of the information traditionally obtained through CMR, potentially offering a more accessible tool for post-infarction risk stratification.

In parallel, circulating microRNAs (miRNAs) have been identified as highly stable, non-invasive biomarkers involved in key biological processes relevant to cardiac remodeling, including fibrosis, apoptosis, angiogenesis, and inflammatory signaling. Several miRNAs have been associated with infarct size, LV dysfunction, and clinical outcomes in patients with acute myocardial infarction. Integrating molecular biomarkers with imaging could provide a powerful multiparametric model for early prediction of AVR, guiding patient-tailored therapeutic strategies.

The SPECTRAMI-CARE study (SPEctral CT and miRna In Acute Myocardial Infarction for Comprehensive Adverse Remodeling Evaluation) is designed as a prospective, multicenter observational cohort. The protocol aims to evaluate the complementary role of spectral CT and circulating miRNAs in predicting adverse remodeling after STEMI with impaired LV function.

Imaging Procedures

Spectral CT:

Performed within the first week after STEMI. Parameters include assessment of infarct size, perfusion defects, myocardial edema, and complications (e.g., thrombus, aneurysm). Quantitative indices will be derived from material decomposition images, iodine density maps, and virtual monoenergetic reconstructions.

Cardiac MRI (sub-cohort):

Used as a reference standard for infarct size, microvascular obstruction, and myocardial viability. Data will be compared with spectral CT findings for concordance and accuracy.

Echocardiography:

Performed at baseline and follow-up for routine functional assessment (LV volumes, LVEF, diastolic function, right ventricular parameters).

Molecular Biomarker Assessment Peripheral blood samples will be collected at baseline (≤72h after PCI), at 1 month, and at 3 months. miRNA profiling will be performed using next-generation sequencing and validated with quantitative RT-PCR. Candidate miRNAs previously implicated in fibrosis, apoptosis, angiogenesis, and remodeling will be specifically analyzed. Expression levels will be correlated with imaging findings and clinical outcomes.

Statistical Analysis Sample size will be based on expected incidence of AVR (~30% in high-risk STEMI populations). Multivariable logistic regression and Cox proportional hazards models will be used to identify predictors of AVR and clinical outcomes. Model performance will be evaluated using C-statistics, calibration plots, and net reclassification improvement (NRI). Internal validation will be performed with bootstrapping; external validation will be explored in an independent cohort.

Ethics and Dissemination The study will comply with the Declaration of Helsinki and local ethics regulations. Informed consent will be obtained from all participants. Data will be anonymized and stored securely. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences, with the aim of contributing to precision medicine in post-infarction care.

Significance SPECTRAMI-CARE is expected to provide novel insights into the early identification of patients at risk for adverse remodeling after STEMI. By integrating cutting-edge imaging and molecular biomarkers, this study seeks to advance risk stratification and facilitate personalized strategies to improve outcomes. Spectral CT, if validated against CMR, may offer a more accessible alternative for myocardial tissue characterization, while circulating miRNAs may add a non-invasive layer of biological information. The multiparametric model proposed has the potential to change clinical practice by identifying high-risk patients earlier and enabling targeted therapeutic interventions.

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Beatriz Martín Carro, PhD; Phone Number: +34923291200; Email: bmartincar.ibsal@saludcastillayleon.es
• Study Contact Backup: Name: Candelas Perez del Villar, MD in Cardiology; Phone Number: +34923291200; Email: mcperezvi@saludcastillayleon.es

Study Locations

• Spain
  • Madrid, Spain
    • Hospital Ramon y Cajal
    • Contact: Juan Manuel Monteagudo Ruiz, MD in Cardiology; Phone Number: 913 36 80 00; Email: j5469m@gmail.com
  • Madrid, Spain
    • Hospital La Princesa
    • Contact: Beatriz López Melgar, MD; Phone Number: 915 20 22 00; Email: blopezm@salud.madrid.org
  • Madrid, Spain
    • Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    • Contact: Carlos Galán Arriola, PhD; Phone Number: 914 53 12 00; Email: carlos.galan@cnic.es
  • Salamanca, Spain
    • Complejo Asistencial Universitario de Salamanca
    • Contact: Candelas Perez del Villar, MD in Cardiology; Phone Number: +34923291200; Email: mcperezvi@saludcastillayleon.es
    • Contact: Beatriz Martín Carro, PhD; Email: bmartincar.ibsal@saludcastillayleon.es
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia
    • Contact: Víctor Marcos Garcés; Email: vic_mg_cs@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults ≥18 years.
• First STEMI treated with primary PCI.
• Left ventricular ejection fraction (LVEF) ≤45% during index hospitalization.
• Ability to provide informed consent.

Exclusion Criteria:

• Contraindication to iodinated contrast media.
• Chronic kidney disease with eGFR <30 mL/min/1.73 m².
• Prior myocardial infarction or known cardiomyopathy.
• Contraindication to CT or MRI imaging.
• Life expectancy <1 year due to non-cardiac conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; At the coordinating center (CAUSA), a control group (n = 20) will be included, consisting of patients with a clinical indication for cardiac CT for reasons other than myocardial infarction, meeting the following criteria: absence of myocardial injury or structural heart disease, ≤1 cardiovascular risk factor, LVEF > 55%, and no significant valvular disease (grade < III).	Procedure: Blood analysis and spectral CT study; Patients who meet the inclusion criteria for the control group will be invited to participate in the study. They will undergo blood sampling and the planned spectral CT study, including a late iodine enhancement acquisition.
Experimental: Adult patients experiencing a first ST-segment elevation myocardial infarction (STEMI); Patientes will be included in this group if the following requirements are met: Hospital admission due to STEMI, treated in accordance with current clinical practice guidelines. Left ventricular systolic dysfunction, defined as a left ventricular ejection fraction (LVEF) < 50%, assessed by transthoracic echocardiography (TTE) within the first 24-72 hours of admission. Provision of signed informed consent.	Procedure: Blood analysis, spectral CT scan and cardiac magnetic resonance imaging (CMR) study; After providing informed consent, patients will undergo blood sampling, a spectral CT scan scheduled between the 3rd and 7th day of hospitalization (acute phase), and a cardiac magnetic resonance imaging (CMR) study performed within a maximum of 72 hours from the CT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse ventricular remodeling at 6 months, defined as an increase in LV end-diastolic volume ≥20% compared with baseline.	The primary endpoint will be the occurrence of adverse ventricular remodeling (AVR) as assessed by cardiac magnetic resonance imaging (CMR). AVR will be defined as an increase in left ventricular end-diastolic volume (LVEDV) of ≥20% compared with baseline values obtained during the acute phase (3-7 days post-STEMI). In cases where CMR is not feasible, spectral CT-derived LV volumes will be used as a contingency reference, given their validated correlation with CMR measurements.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size characterization by spectral CT vs. CMR.	Quantitative assessment of infarct size will be performed using spectral CT (late iodine enhancement, iodine concentration maps, and non-contrast acquisitions for edema) and compared with CMR (late gadolinium enhancement, T1/T2 mapping, and extracellular volume fraction).	Baseline and 6 months
Myocardial characterization by spectral CT vs. CMR.	Quantitative assessment of myocardial markers such as microvascular obstruction (MVO), intramyocardial hemorrhage, and myocardial edema will be evaluated to determine the diagnostic accuracy and reproducibility of spectral CT (late iodine enhancement, iodine concentration maps, and non-contrast acquisitions for edema) and compared with the gold standard CMR (late gadolinium enhancement, T1/T2 mapping, and extracellular volume fraction).	Baseline and 6 months
Correlation of miRNA signatures with remodeling.	Serum miRNA profiles obtained at baseline (acute phase) and at 6 months will be analyzed to identify differential expression patterns associated with adverse remodeling. Specific miRNAs previously linked to fibrosis, apoptosis, and inflammation (e.g., miR-1, miR-21, miR-30a-5p, miR-133a, miR-210-3p, miR-221-3p) will be quantified by RT-qPCR. Qualitative correlation between miRNA expression levels and imaging-defined markers of remodeling will be tested, including potential sex-specific differences.	Baseline and 6 months
Predictive accuracy of integrated models (spectral CT + miRNA vs. conventional predictors)	Predictive models will be developed combining spectral CT-derived parameters, miRNA signatures, and conventional clinical predictors (age, sex, infarct location, Killip class, biomarkers). Model performance will be assessed using machine learning approaches (logistic regression, random forest, XGBoost), with internal validation through repeated 10-fold cross-validation. Predictive accuracy will be reported using receiver-operating characteristic (ROC) curves, area under the curve (AUC), calibration statistics, and Shapley values for interpretability. All parameters sill be used simultaneously to predict integrated models, therefore they cannot be sepparated in different outcomes.	6 months
Major adverse cardiovascular events (MACE)	The composite endpoint of MACE will include cardiovascular death, recurrent myocardial infarction, and hospitalization for heart failure during the 12-month follow-up period. All events will be adjudicated by an independent clinical events committee, blinded to imaging and biomarker results.	From baseline to 6 months
Safety outcomes: incidence of contrast-induced nephropathy	Safety outcomes will be carefully annotated, including incidence of contrast-induced nephropathy (defined as a ≥30% decline in estimated glomerular filtration rate compared with baseline).	From baseline to 6 months
Safety outcomes: allergic or hypersensitivity reactions	Aallergic or hypersensitivity reactions to iodinated contrast or gadolinium-based agents will be assessed.	From baseline to 6 months
Safety outcomes: arrhythmias related to imaging procedures	Arrhythmias temporally related to imaging procedures (e.g., during CT or CMR acquisition) will be evaluated.	From baseline to 6 months
Safety outcomes: Cumulative radiation exposure	Cumulative radiation exposure from spectral CT will also be recorded and reported as an additional safety metric.	From baseline to 6 months

Collaborators and Investigators

• Sponsor: Instituto de Investigación Biomédica de Salamanca

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Estimated): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: myocardial infarction; miRNA; magnetic resonance; adverse ventricular remodeling; spectral computed tomography
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Myocardial Infarction; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests
• Other Study ID Numbers: SPECTRAMI-CARE; PI2025 03 1870 (Other Identifier: Ethics Committee for Clinical Research, Salamanca)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Plan Description: De-identified individual participant-level data (IPD) will be shared, including:

Demographic and clinical variables collected in REDCap. Quantitative spectral CT parameters (iodine maps, first-pass perfusion, late iodine enhancement, volumetric data).

Cardiac MRI parameters (volumes, T1/T2 mapping, ECV, MVO, IMH). Serum miRNA panel results (derived files and processed tables). Clinical outcomes (adverse ventricular remodeling defined by indexed EDV/ESV, 1-year MACE, renal function, etc.).

Supporting documents (data dictionary, eCRFs, analysis scripts in R/Python when available, FAIR metadata) will also be provided.

• IPD Sharing Time Frame: Beginning 12 months after publication of primary results, available for at least 5 years.

IPD Sharing Access Criteria

Access Criteria: Access will be granted to qualified researchers with a methodologically sound proposal. Requests will be reviewed by the study Data Committee/steering committee. Applications must be addressed to the PI (Candelas Pérez del Villar). Requirements include: Data Use Agreement (DUA), commitment to non-reidentification, appropriate data security, mandatory citation of dataset source and DOI. Analytical code sharing and a publication plan may be required prior to access approval.

IPD Sharing Support: Data will be hosted on controlled project infrastructure (XNAT/Core-lab) and disseminated through the IBSAL Zenodo community with DOI and regulated access, in compliance with GDPR/LOPDGDD and CEIm approval.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No