Atrial Cardiomyopathy in Patients With Cardiovascular-Kidney-Metabolic Syndrome: Non-invasive Characterization (ATRIO-CKM)

Atrial Cardiomyopathy in Patients With Cardiovascular-Kidney-Metabolic Syndrome: Non-invasive Characterization (ATRIO-CKM)

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder characterized by pathophysiological interactions among metabolic risk factors, chronic kidney disease, and the cardiovascular system, leading to multiorgan dysfunction and increased risk of atrial fibrillation, stroke, and heart failure. Atrial cardiomyopathy (ACM) - defined as any structural, contractile, or electrical abnormality of the atria - is an increasingly recognized contributor to cardiovascular morbidity and mortality in this population. Despite growing interest in both conditions, their interplay remains poorly understood, limiting effective preventive strategies and risk-stratification approaches for this high-risk group.

CKM staging offers a practical framework for anticipating ACM onset and progression. Because adiposity-driven inflammation, insulin resistance, hypertension, and early kidney injury act as upstream drivers in CKM, the left atrium becomes an early indicator of hemodynamic load and fibrosis - often preceding sustained atrial fibrillation. Early non-invasive detection of ACM across CKM stages could shift care from treating complications to modifying the underlying substrate.

This prospective observational single-center cohort study aims to phenotype ACM non-invasively across all CKM stages at first diagnosis, using standard 12-lead ECG, advanced transthoracic echocardiography with speckle-tracking, a mechanistically selected biomarker panel (NT-proBNP, MR-proANP, Fetuin-A, FGF23), and cardiac MRI.

Adults aged 18 years or older presenting for cardiovascular evaluation are enrolled and grouped as CKM with ACM (study group) versus CKM without ACM (control group). All participants undergo a single standardized baseline evaluation including clinical examination, 12-lead ECG with Bayés interatrial block grading, comprehensive laboratory panel, and advanced echocardiography including left atrial global longitudinal strain by speckle-tracking.

Primary objective: characterize the relationship between ACM and CKM syndrome stages using non-invasive parameters at first diagnosis. Secondary objectives include assessment of clinical, biological, ECG, and imaging profiles of ACM in CKM; evaluation of left atrial function across CKM stages; examination of Bayés interatrial block correlations and the impact of SGLT2 inhibitors and GLP-1 receptor agonists on left atrial remodeling in HFpEF; and identification of independent ACM risk factors incorporating the full biomarker panel.

Statistical analyses include multivariable logistic regression, biomarker ROC analyses, and penalized regression for derivation of a pragmatic ACM risk score with internal validation. Expected outputs include prevalence estimates, effect sizes for ACM and CKM joint categories, biomarker performance metrics, and a clinic-ready checklist for risk-stratified prevention in outpatient settings.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Metabolic Syndrome; Chronic Kidney Disease; Atrial Cardiomyopathy; Cardiovascular-Kidney-Metabolic Syndrome

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Mariana M Floria, MD, PhD; Phone Number: +40722364423; Email: floria.mariana@umfiasi.ro
• Study Contact Backup: Name: Maria Mihaela M Godun, MD; Phone Number: +40755777809; Email: maria_godun@yahoo.com

Study Locations

• Romania
  • Iaşi
    • Iași, Iaşi, Romania, 700111
      • Internal Medicine Clinic I "Prof. Datcu" - Sf. Spiridon County Emergency Clinical Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults presenting for cardiovascular evaluation at the Internal Medicine I Department, Sf. Spiridon County Emergency Clinical Hospital Iasi, Romania, with cardiovascular-kidney-metabolic syndrome.

Description

Inclusion Criteria:

• Adults aged 18 years or older presenting for cardiovascular evaluation Signed written informed consent Agreement with all protocol requirements

Exclusion Criteria:

• Missing key data for ACM or CKM classification Hemodynamically significant valvular heart disease (greater than moderate severity) Mechanical or biological valve prostheses Temporary or permanent cardiac pacing Psychiatric pathology Thyroid pathology (active or untreated) Known cardiomyopathies (hypertrophic, dilated, restrictive, or infiltrative) Refusal to participate or inability to comply with protocol requirements

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
CKM with ACM; Patients with cardiovascular-kidney-metabolic syndrome and atrial cardiomyopathy, defined by presence of Bayés interatrial block on 12-lead ECG and/or reduced left atrial global longitudinal strain and/or elevated left atrial volume index on echocardiography
CKM without ACM; Patients with cardiovascular-kidney-metabolic syndrome without atrial cardiomyopathy, serving as the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of atrial cardiomyopathy (ACM) across CKM syndrome stages	Prevalence of ACM defined by presence of Bayés interatrial block (grade 1 or 2) on 12-lead ECG and/or reduced left atrial global longitudinal strain and/or elevated left atrial volume index on transthoracic echocardiography, across CKM syndrome stages 0-4	Baseline (single evaluation visit)

Secondary Outcome Measures

Outcome Measure	Time Frame
Left atrial reservoir strain (LA-GLS %) across CKM syndrome stages assessed by speckle-tracking echocardiography	Baseline
Prevalence and grading of Bayés interatrial block and correlation with CKM-specific variables	Baseline
Distribution of biomarker levels (Fetuin-A, MR-proANP, FGF23, NT-proBNP) across ACM and CKM categories	Baseline
Independent risk factors for ACM in CKM syndrome identified by multivariable logistic regression incorporating clinical, ECG, echocardiographic and biomarker variables	Baseline

Collaborators and Investigators

• Sponsor: Grigore T. Popa University of Medicine and Pharmacy
• Investigators: Study Director: Marius T Marcu, MD, PhD, Grigore T. Popa University of Medicine and Pharmacy Iasi; Study Chair: Mugurel C Apetrii, MD, PhD, Grigore T. Popa University of Medicine and Pharmacy Iasi; Study Chair: Anca E Stefan, MD, Grigore T. Popa University of Medicine and Pharmacy Iasi; Study Chair: Laura Huiban, MD, PhD, Grigore T. Popa University of Medicine and Pharmacy Iasi; Study Chair: Alexandru F Oancea, MD, Grigore T. Popa University of Medicine and Pharmacy Iasi

Study record dates

Study Major Dates

• Study Start (Estimated): July 10, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: July 5, 2026
• First Submitted That Met QC Criteria: July 5, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Chronic Kidney Disease; FGF23; speckle tracking; Fetuin-A; MR-proANP; atrial cardiomyopathy; atrial remodeling; CKM syndrome; on-invasive evaluation; Bayés interatrial block
• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Pathological Conditions, Anatomical; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Chronic Disease; Disease Attributes; Metabolic Diseases; Arrhythmias, Cardiac; Glucose Metabolism Disorders; Renal Insufficiency; Insulin Resistance; Hyperinsulinism; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Metabolic Syndrome; Atrial Fibrillation; Renal Insufficiency, Chronic; Atrial Remodeling
• Other Study ID Numbers: ATRIO-CKM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data and analysis code will be shared where permitted by ethics approval and institutional policy. A synthetic dataset may be provided if full de-identification is not feasible.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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