Atrial Fibrillation in Relationship to Plasma Biomarkers (AFISBIO II)

The general objective of this study is to:

A. To identify novel plasmatic biomarkers associated with prevalent/incident atrial fibrillation in patients with high risk for AF and stroke.

B. To assess predictive ability of novel plasmatic biomarkers (especially apelin and miRNAs) on prevalent/incident atrial fibrillation in patients with high risk for AF and stroke.

C. To validate predictive models from previous studies based on comorbidities, age, sex, BMI, NT-proBNP, FGF-23, IGF-1 and IGFBP-1 on prevalent/incident AF in patients with high risk for AF and stroke.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Diagnostic test: Peripheral blood samples for routine analysis including NT-proBNP and plasmatic biomarkers.; Diagnostic test: Echocardiography; Diagnostic test: ECG Holter monitor; Diagnostic test: Standardized Mini-Mental Status Exam (SMMSE)

Detailed Description

Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with an increased risk of stroke, heart failure, and mortality. Despite the high prevalence, AF may be asymptomatic and consequently unrecognized. Detection of asymptomatic AF is challenging as only a minority of the patients is diagnosed during standard examinations with a 12 - lead ECG or a 24h ECG Holter monitoring. Furthermore, prolonged ECG monitoring is costly and can be inconvenient for the patients. Documented AF causes 15% of ischemic strokes. However, approximately 25% of ischemic strokes is of an unknown etiology. It is believed that undetected asymptomatic AF is responsible for some of these strokes.

Plasmatic biomarkers might be of importance in the early diagnosis of AF. Several plasmatic biomarkers have been studied in order to find an association with AF. Cardiac biomarkers such as natriuretic peptides and high-sensitivity troponins are increased in patients with AF. A novel biomarker that is depending on left atrial stretching and ionotropic effects is apelin. In our previous research we discovered that apelin is associated with AF, negatively correlates with AF burden, but only in patients without reduced LVEF. Similarly, parameters reflecting thrombogenesis, such as Fibrinogen and fibrin D-dimer were also found to be associated with the arrhythmia. Other protein biomarkers have been studied in relation to AF incidence. Insulin-like growth factor-binding protein 1 (IGFBP-1) and Insulin-like growth factor 1 (IGF-1) have shown an association with higher risk of incident AF. Previous research also indicated Fibroblast growth factor 23 (FGF-23) to be associated with AF.

However, biomarkers, such as the inflammatory markers high-sensitivity CRP have shown conflicting results.

Finally, in the last years, circulating microRNAs emerged as a promising biomarker of AF, having important function in suppression of messenger RNA responsible for electric and structural remodeling of the left atria.

In our previous case-matched study we discovered that selected miRNAs were associated with paroxysmal AF.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Allan Böhm, MD, PhD, MBA, FESC; Phone Number: +421 907 411 499; Email: allan.bohm@gmail.com

Study Locations

• Slovakia
  • Bratislava, Slovakia, 813 69
    • Recruiting
    • University Hospital Bratislava - Old Town Hospital
    • Contact: Martin Čaprnda, MD, PhD
    • Principal Investigator: Martin Čaprnda, MD, PhD
  • Bratislava, Slovakia, 826 06
    • Recruiting
    • University Hospital Bratislava - Hospital Ruzinov
    • Contact: Ján Páleš, MD
    • Principal Investigator: Ján Páleš, MD
  • Bratislava, Slovakia, 833 05
    • Recruiting
    • University Hospital Bratislava - Hospital of the Academician Ladislav Dérer
    • Contact: Tereza Hlavatá, MD
    • Principal Investigator: Tereza Hlavatá, MD
  • Bratislava, Slovakia, 833 48
    • Recruiting
    • National Institute for Cardiovascular Diseases
    • Contact: Allan Böhm, PhD, MBA, FESC; Phone Number: +421 907 411 499; Email: allan.bohm@gmail.com
    • Principal Investigator: Allan Böhm, PhD, MBA, FESC
  • Malacky, Slovakia
    • Recruiting
    • Hospital Malacky
    • Contact: Tomáš Uher, MD
    • Principal Investigator: Tomáš Uher, MD
  • Nitra, Slovakia, 950 01
    • Recruiting
    • Faculty Hospital Nitra
    • Contact: Peter Snopek, MD
    • Principal Investigator: Peter Snopek, MD
    • Sub-Investigator: Radovan Hurčík, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients from Slovak hospitals and outpatient clinics in sinus rhythm without history of AF, with high risk for ischemic stroke and AF. CHA2DS2-VASc score > 2 (for females > 3) and with more than 3 specific criteria for inclusion.

Description

Inclusion Criteria:

General inclusion criteria:

• AGE > 50 years
• No history of supraventricular arrhythmia
• Sinus rhythm at inclusion
• CHADSVASc score > 2 in men (> 3 in female)
• More than 3 specific criteria for inclusion
• Written informed consent is obtained before any study-related assessment is performed

Specific inclusion criteria:

• Age > 65
• Age > 75
• BMI > 30
• Heart failure with preserved LVEF (according to ESC GL for HF)
• Ischemic stroke
• Left atrial diameter > 45mm
• Chronic obstructive pulmonary disease
• Arterial hypertension
• PR interval > 200ms
• History of MI or (objective evidence of) chronic coronary syndrome
• Peripheral artery disease
• Thyroid disease

Exclusion Criteria:

• History of any supraventricular or ventricular arrhythmia (excluding premature contractions and 1st degree AV block)
• Therapy with anticoagulants at the time of inclusion
• Acute coronary syndrome less than 1 month prior to inclusion
• History of cardiac surgery
• Diabetes mellitus type 2
• Reduced LVEF (<50%)
• Acute or decompensated heart failure at the time of inclusion
• Cardiomyopathy
• Systemic inflammatory disease or acute inflammatory disease
• Active malignancy
• Alcoholism (≥ 8 drinks/week)
• Renal Disease (Dialysis/ transplant/ CrCl < 1ml/s)
• Liver disease (cirrhosis/ transaminase > 3x ULT/ bilirubin > 2x ULT)
• Severe or moderate mitral stenosis
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study Group; Patients in sinus rhythm without history of AF, with high risk for ischemic stroke and AF. CHA2DS2-VASc score > 2 (for females > 3) and with more than 3 specific criteria for inclusion.

Diagnostic test: Peripheral blood samples for routine analysis including NT-proBNP and plasmatic biomarkers.; Sampling of peripheral venous blood for analysis of plasma concentration of plasmatic markers (Apelin, microRNA, FGF-23, IGF-1, IGFBP-1) and routine analysis (laboratory parameters: NT-proBNP, D-dimer, Creatinine Clearance, CRP, Hs-troponin).; Diagnostic test: Echocardiography; ECHO parameters: E/e´; Mean e' septal and lateral wall; LA volume (Biplane Area-Length Method); Left atrial volume index; Diameter of left atrium in PLAX; Severe aortic stenosis; Severe mitral regurgitation; Severe tricuspid regurgitation; Left ventricular end-diastolic diameter; Interventricular septum; Posterior wall; LV Mass; Left ventricular mass index; Diagnostic test: ECG Holter monitor; Patient receives an ECG Holter for a 7-day monitoring.; Diagnostic test: Standardized Mini-Mental Status Exam (SMMSE); A screening test for evaluating cognitive performance of patients done in the clinician's office.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of AF	AF duration > 30s on surface ECG	Within 14 days from Inclusion.
Incidence of AF	AF duration > 30s on surface ECG	Within 14 days from Inclusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular (CV) death	Event occurred or did not occur (Yes/No).	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
All cause death	Event occurred or did not occur (Yes/No).	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
CV death + nonfatal stroke + nonfatal myocardial infarction	Event occurred or did not occur (Yes/No).	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
Ischemic stroke	Event occurred or did not occur (Yes/No).	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
Cognitive decline assessed by Mini-Mental State Examination	Impairment observed and recorded or not observed and not recorded (Yes/No).	Day 350-380 from inclusion (Follow-up 4) - Day 1080-1110 from inclusion (Follow-up 6)
Heart failure	Event occurred or did not occur (Yes/No). If Yes, HF classification to be indicated based on LVEF: i. with preserved LVEF (HFpEF) ii. with mid-range LVEF (HFmrEF) iii. with reduced LVEF (HFrEF)	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
Hospitalization due to CV cause	Event occurred or did not occur (Yes/No).	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)
Acute coronary syndrome	Event occurred or did not occur (Yes/No). If Yes, type of ACS to be indicated: i. Unstable angina ii. NSTEMI iii. STEMI	Day 175-205 from inclusion (Follow-up 3) - Day 1080-1110 from inclusion (Follow-up 6)

Collaborators and Investigators

• Sponsor: Premedix Academy

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: January 10, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 13, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; ECG Monitoring; Plasmatic Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 0012020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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