Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers
- Conditions
- Atrial Fibrillation
- Interventions
- Diagnostic Test: ECHOcardiographyDiagnostic Test: Peripheral blood samples for plasmatic biomarkersDiagnostic Test: Athens insomnia scale questionnaireDiagnostic Test: ECG Holter monitorDiagnostic Test: ECG event recorder
- Registration Number
- NCT03855540
- Lead Sponsor
- Premedix Academy
- Brief 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
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
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 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Control group ECG Holter monitor 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) Control group ECHOcardiography 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) Control group Athens insomnia scale questionnaire 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) Study group Athens insomnia scale questionnaire 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. Study group ECHOcardiography 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. Control group ECG event recorder 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) Study group Peripheral blood samples for plasmatic biomarkers 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. Control group Peripheral blood samples for plasmatic biomarkers 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)
- Primary Outcome Measures
Name Time Method Plasmatic biomarkers Day of inclusion Compare the plasmatic biomarkers between the cohort with and without atrial fibrillation:
1. Coagulation a D - dimer b Fibrinogen
2. Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE
3. Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin
4. MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328Quality of sleep Day of inclusion 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.
- Secondary Outcome Measures
Name Time Method Diagnostic plasmatic biomarker Day of inclusion Find sensitive and specific biomarker that could be used for the diagnostic management of atrial fibrillation:
1. Coagulation a D - dimer b Fibrinogen
2. Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE
3. Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin
4. MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328
Trial Locations
- Locations (4)
Allan Bohm
🇸🇰Bratislava, Slovakia
East Slovak Institute of Cardiovascular Diseases
🇸🇰Košice, Slovakia
Hospital
🇸🇰Malacky, Slovakia
University hospital
🇸🇰Nitra, Slovakia