Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers (AFISBIO)

AFISBIO - Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers.

A. Compare the plasmatic biomarkers between the cohort with and without AFib.

B. Find sensitive and specific biomarkers that could be used for the diagnostic management of AFib.

C. Compare the quality of sleep between the cohort with and without AFib by the means of sleeping quality questionnaire

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Diagnostic test: ECHOcardiography; Diagnostic test: Peripheral blood samples for plasmatic biomarkers; Diagnostic test: Athens insomnia scale questionnaire; Diagnostic test: ECG Holter monitor; Diagnostic test: ECG event recorder

Detailed Description

AFib is the most common sustained arrhythmia, associated with an increased risk of stroke, heart failure, and mortality. Despite the high prevalence, AFib may be asymptomatic and consequently subclinical. Detection of subclinical AFib is highly challenging as only a minority of the patients is diagnosed during a standard examinations with a 12 - lead ECG or a 24h ECG Holter monitoring. Documented AFib causes 15% of ischemic strokes, however approximately 25% of ischemic strokes is of an unknown etiology. It is believed that undetected subclinical AFib is responsible for these strokes. There is also evidence that asymptomatic AFib is associated with a higher incidence of strokes in comparison to symptomatic AFib.

Due to the fact that the standard ECG examination is not sufficient for AFib detection, various ECG screening methods have been introduced. Intermittent short ECG recording seems to be more effective than 24-hour Holter ECG in the detection of the arrhythmia however, it is not known whether it is superior to the 7 - day ECG Holter monitoring.

Plasmatic biomarkers might be of a paramount importance in the diagnostic management.

Several plasmatic biomarkers were tested to find an association with AFib. Perhaps the most studied ones were the natriuretic peptides that showed to be significantly increased in patients with AFib. Similarly, high sensitivity troponins are elevated in patients with the AFib. Another marker of left atrial stretching and also of ionotropic effects is apelin. Patients with lone AFib showed a significantly decreased levels of this peptide. Conflicting results were shown in studies with inflammatory biomarkers such as high sensitivity CRP Parameters reflecting thrombogenesis were also found to be associated with the arrhythmia. Fibrinogen and fibrin D-dimer were significantly increased in paroxysmal AFib. Finally, in the last years, the circulating micro RNAs emerged as a promising biomarker of AFib, having important function in suppression of messenger RNA responsible for thrombogenesis and ionotropic functions.

The weakness of the mentioned studies is, that the biomarkers were usually tested in patients with a few comorbidities. So, it is not known whether these biomarkers are specific for AFib "per se" or whether they just reflect pathophysiological mechanisms like inflammation, fibrogenesis or left atrium stretching that is also present in other cardiovascular diseases. Furthermore, the AFib cohorts were often not matched with the control groups adding more uncertainty. To clarify these questions, we designed a study where plasmatic biomarkers will be studied in high risk cohort of patients with AFib having several cardiovascular comorbidities. These patients will be subsequently matched with a control group according to the age, gender and the cardiovascular comorbidities.

Similarly, as the continuum of organic changes of the heart from the left ventricular diastolic dysfunction, left atrial dilatation ending with heart failure, there is also "arrhythmology continuum" in patients with arterial hypertension to supraventricular premature contractions via paroxysmal tachycardia of fibrillation up to the permanent atrial fibrillation (AFib). A common etiopathology factor of these disorders is increased sympathetic activity, which together with the catecholamine release during the stress causes arrhythmogenic substrates due to the atrial fibrogenesis. The relation between sleep disorders and the AFib is poorly understood. Micro awakenings during the night increases sympathetic activity and the arterial blood pressure. Other possible mechanism might be the decrease of plasmatic melatonin related to aging. Sleep disorders are linked to the increased heart rate, worsening of the heart rate variability, increased metabolism and body temperature, increased beta EEG activity and activation of the hypothalamic - pituitary - adrenal axis. In patients with arterial hypertension, there is an increased occurrence of premature atrial contractions that is linked to increased risk of AF incidence.

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

Contacts and Locations

Study Locations

• Slovakia
  • Bratislava, Slovakia, 81102
    • Recruiting
    • Allan Bohm
    • Contact: Allan Bohm, MD; Phone Number: 0259320111; Email: allan.bohm@gmail.com
  • Košice, Slovakia
    • Recruiting
    • East Slovak Institute of Cardiovascular Diseases
    • Contact: Marianna Vachalcová, MD; Phone Number: 421914241352; Email: vachalcova@gmail.com
  • Malacky, Slovakia
    • Recruiting
    • Hospital
    • Contact: Tomas Uher, MD; Email: uher@gmail.com
  • Nitra, Slovakia
    • Recruiting
    • University Hospital
    • Contact: Peter Snopek, MD; Email: snopek@gmail.com
    • Contact: Viera Kissová, MD
    • Sub-Investigator: Monika Urbanová, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Slovak hospitals and outpatients clinics

Description

Inclusion Criteria: The specific criteria for inclusion in the study group are:

• Age >17 years
• Documented, nonvalvular paroxysmal AFib in the duration of more than 6 min. (medical history or ECG monitoring)
• CHA2DS2-VASc score > 2 for males
• CHA2DS2-VASc score > 3 for females
• Sinus rhythm at the time of inclusion

The specific criteria for inclusion in the control group are:

• No history of palpitations
• AFib exclusion with the 7 days ECG Holter and ECG event recorder monitoring
• Propensity matching

Exclusion Criteria: Exclusion criteria for both groups:

• Electrical cardioversion less than 7 days prior to inclusion
• Acute coronary syndrome less than 1 month prior to inclusion
• Cardiac surgery less than 3 months prior to inclusion
• Acute or decompensated heart failureat the time of inclusion
• Pregnancy
• Cardiomyopathy
• Alcoholism (≥ 8 drinks/week)
• Thyrotoxicosis
• Renal Disease (Dialysis/ transplant/CrCl < 0,5ml/s)
• Liver disease (cirrhosis/ transaminase > 3x ULT/ bilirubin > 2x ULT)
• Mechanical proshetic valves
• Severe mitral stenosis
• Class I and IV antiarrhythmic drugs usage in last month
• Class III antiarrhythmic drugs usagein last 3 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Adult patients with documented paroxysmal, nonvalvular atrial fibrillation with CHA2DS2-VASc score > 2 (for females > 3) and sinus rhythm at the time of inclusion. In total 100 patients will be included.	Diagnostic test: ECHOcardiography; ECHO parameters; LA diameter; LVEDD; LVEF; Diastolic dysfunction; Valvular disease; Diagnostic test: Peripheral blood samples for plasmatic biomarkers; CoagulationD - dimerFibrinogen; Inflammation and fibrosisHs - CRPAGEsSoluble RAGE; Hemodynamics (LA stretch)ApelinNT - proBNPHs - troponin; MiRNAmiRNA - 1miRNA - 133miRNA - 29bmiRNA - 208amiRNA - 208bmiRNA - 499; Diagnostic test: Athens insomnia scale questionnaire; Athens insomnia scale questionnaire
Control group; Patients without a history of palpitations or irregular heart rhythm. AFib will be excluded with the help of 7 days ECG Holter and ECG event recorder monitoring. In total 100 patients will be included. Propensity matching according to the: CHA2DS2-VASc parameters; LVEF: preserved (<40%), mid-range (40-49%) and reduced (>50%); Presence of diastolic dysfunction; Glomerular filtration rate: (≥1,5 ml/s), (1,4-1 ml/s) and (0,9-0,5 ml/s); Drugs: ACE-I/ARB, betablockers, digoxin, amiodarone; BMI: (<30kg/m2), (30-39kg/m2) and (≥40kg/m2); Smoking (>5 cigarettes per day)	Diagnostic test: ECHOcardiography; ECHO parameters; LA diameter; LVEDD; LVEF; Diastolic dysfunction; Valvular disease; Diagnostic test: Peripheral blood samples for plasmatic biomarkers; CoagulationD - dimerFibrinogen; Inflammation and fibrosisHs - CRPAGEsSoluble RAGE; Hemodynamics (LA stretch)ApelinNT - proBNPHs - troponin; MiRNAmiRNA - 1miRNA - 133miRNA - 29bmiRNA - 208amiRNA - 208bmiRNA - 499; Diagnostic test: Athens insomnia scale questionnaire; Athens insomnia scale questionnaire; Diagnostic test: ECG Holter monitor; Patient receives ECG Holter monitor if included to the control group; Diagnostic test: ECG event recorder; Patient receives ECG event recorder for twice daily (or if symptoms), 90 seconds duration ECG monitoring if included to the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasmatic biomarkers	Compare the plasmatic biomarkers between the cohort with and without atrial fibrillation: Coagulation a D - dimer b Fibrinogen; Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE; Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin; MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328	Day of inclusion
Quality of sleep	Compare the quality of sleep between the cohort with and without atrial fibrillation by the means of Athens Insomnia Scale (AIS). It is measured by assessing eight factors amongst which first five factors are related to nocturnal sleep and last three factors are related to daytime dysfunction. These are rated on a 0-3 scale and the sleep is finally evaluated from the cumulative score of all factors and reported as an individual's sleep outcome. A cut-off score of ≥6 on the AIS is used to establish the diagnosis of insomnia.	Day of inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic plasmatic biomarker	Find sensitive and specific biomarker that could be used for the diagnostic management of atrial fibrillation: Coagulation a D - dimer b Fibrinogen; Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE; Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin; MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328	Day of inclusion

Collaborators and Investigators

• Sponsor: Premedix Academy
• Investigators: Principal Investigator: Allan Bohm, MD, The National Institution of Cardiovascular Diseases; Principal Investigator: Stefan Farsky, Associate professor, Slovak league against hypertension

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 11, 2018
• Primary Completion (ANTICIPATED): December 31, 2019
• Study Completion (ANTICIPATED): December 31, 2019

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (ACTUAL): February 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Atrial fibrillation; ECG monitoring; quality of sleep; plasmatic biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 0012018

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