Atrial Fibrillation in Relationship to Plasma Biomarkers

Atrial Fibrillation Clinical Trial

— AFISBIO II  

Official title:

Atrial Fibrillation in Relationship to Plasma Biomarkers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04710745
• Other study ID #: 0012020
• Status: Recruiting
• Start date: December 4, 2020
• Est. completion date: December 2024

Study information

• Verified date: January 2021
• Source: Premedix Academy
• Contact: Allan Böhm, MD, PhD, MBA, FESC
• Phone: +421 907 411 499
• Email: allan.bohm[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

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).
• 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
• ECG Holter monitor
Patient receives an ECG Holter for a 7-day monitoring.
• Standardized Mini-Mental Status Exam (SMMSE)
A screening test for evaluating cognitive performance of patients done in the clinician's office.

Locations

Country	Name	City	State
Slovakia	National Institute for Cardiovascular Diseases	Bratislava
Slovakia	University Hospital Bratislava - Hospital of the Academician Ladislav Dérer	Bratislava
Slovakia	University Hospital Bratislava - Hospital Ruzinov	Bratislava
Slovakia	University Hospital Bratislava - Old Town Hospital	Bratislava
Slovakia	Hospital Malacky	Malacky
Slovakia	Faculty Hospital Nitra	Nitra

Sponsors (1)

Lead Sponsor	Collaborator
Premedix Academy

Country where clinical trial is conducted

Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of AF	AF duration > 30s on surface ECG	Within 14 days from Inclusion.
Primary	Incidence of AF	AF duration > 30s on surface ECG	Within 14 days from Inclusion.
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)