Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers

Atrial Fibrillation Clinical Trial

— AFISBIO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03855540
• Other study ID #: 0012018
• Status: Recruiting
• Start date: April 11, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: March 2019
• Source: NGO: Research Institute of Academy
• Contact: Allan Bohm, MD
• Phone: +421259320111
• Email: allan.bohm[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Diagnostic Test:
• ECHOcardiography
ECHO parameters LA diameter LVEDD LVEF Diastolic dysfunction Valvular disease
• Peripheral blood samples for plasmatic biomarkers
Coagulation D - dimer Fibrinogen Inflammation and fibrosis Hs - CRP AGEs Soluble RAGE Hemodynamics (LA stretch) Apelin NT - proBNP Hs - troponin MiRNA miRNA - 1 miRNA - 133 miRNA - 29b miRNA - 208a miRNA - 208b miRNA - 499
• Athens insomnia scale questionnaire
Athens insomnia scale questionnaire
• ECG Holter monitor
Patient receives ECG Holter monitor if included to the control group
• 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

Locations

Country	Name	City	State
Slovakia	Allan Bohm	Bratislava
Slovakia	East Slovak Institute of Cardiovascular Diseases	Košice
Slovakia	Hospital	Malacky
Slovakia	University hospital	Nitra

Sponsors (1)

Lead Sponsor	Collaborator
NGO: Research Institute of Academy

Country where clinical trial is conducted

Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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