Atrial Cardiomyopathy in Patients With Cardiovascular-Kidney-Metabolic Syndrome: Non-invasive Characterization

NCT07697469 | Not Yet Recruiting

• 1 other identifier: ATRIO-CKM
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular-Kidney-Metabolic Syndrome; Atrial Cardiomyopathy; Atrial Fibrillation; Chronic Kidney Disease; Metabolic Syndrome

Keywords

atrial cardiomyopathy; CKM syndrome; on-invasive evaluation; atrial remodeling; Bayés interatrial block; speckle tracking; Fetuin-A; MR-proANP; FGF23; Atrial Fibrillation; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grigore T. Popa University of Medicine and Pharmacy: lead

Study Sites (1)

Internal Medicine Clinic I "Prof. Datcu" - Sf. Spiridon County Emergency Clinical Hospital

Iași, Iaşi, 700111, Romania

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and plasma samples stored at -80°C for batch analysis by ELISA (MR-proANP,). Samples will be analyzed within 6 months of collection and discarded after analysis. No long-term biobank retention is planned.

MeSH Terms

Conditions

Atrial Fibrillation; Renal Insufficiency, Chronic; Metabolic Syndrome; Atrial Remodeling

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathological Conditions, Anatomical

Study Officials

• Marius T Marcu, MD, PhD

  Grigore T. Popa University of Medicine and Pharmacy Iasi

  STUDY DIRECTOR

• 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 CHAIR

Central Study Contacts

Mariana M Floria, MD, PhD

CONTACT

+40722364423; floria.mariana@umfiasi.ro

Maria Mihaela M Godun, MD

CONTACT

+40755777809; maria_godun@yahoo.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 5, 2026
• First Posted: July 13, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

RO (1)