Predictive Properties of Myocardial Fibrosis Biomarkers on the Outcome of Atrial Fibrillation Ablation (PROFIB-AF)

Atrial fibrillation (AF) is the most common cardiac arrhythmia. As an independent predictor of cardiovascular mortality, particularly for stroke, its management is a real public health issue. AF is associated with diabetes, obesity, hypertension, heart failure and, occasionally, hyperthyroidism. Atrial fibrosis is one of the major players in the genesis and maintenance of AF. It has a strong impact on rhythmic prognosis and treatment success.

Currently the AF ablation is the treatment recommended by the European Society of Cardiology (ESC) and by the American Society of Cardiology. The rate of AF recurrence is variable according to the patient characteristics and remains unfortunately today difficult to predict.

Abnormal concentrations of circulating biomarkers reflecting the underlying pathophysiologic mechanisms of myocardial fibrosis could help to identify patients at higher risk of developing AF and/or AF recurrence after ablation. Thus, the development of simple, reliable and valid biological tests of atrial fibrosis would allow the clinicians i) to estimate the potential success of AF ablation; ii) to predict AF recurrence; iv) and to propose a AF personalized therapeutic approach.

The main objective of PROFIB-AF study is to identify, among biological markers (ICTP, PICP, PIIINP, sRAGE, AGE, Galectin 3, sSt2, microRNAs) of myocardial fibrosis, those which can predict the recurrence risk after AF ablation.

Study Overview

• Status: Recruiting
• Conditions: Women and Men Over 18 Years Old; AF Ablation (ECS recommendation2020&ACS2014) Either for Paroxysmal AF Unresponsive to Anti-arrhythmic Treatment Either for Persisting Symptomatic AF; Able to Give His Non Opposition to Participate to the Study

Detailed Description

Patients prone to AF ablation and do not object to participate at PROFIB-AF study will be offered, in parallel of their conventional care, blood samples the day of AF ablation by femoral and sinusal punctures and 12 months after ablation by venipuncture for the biomarkers analysis.

As part of their traditional care, these patients will benefit several exams beforeAF ablation (MRI, clinical examination ECG, echocardiography, routine biological analyzes), and four follow-up visits after AF ablation (at 3, 6, 9 and 12 months post-ablation) to evaluate AF recurrence, occurrence of MACE and heart failure signs.

• Study Type: Observational
• Enrollment (Anticipated): 190

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • Recruiting
    • CHU Clermont-Ferrand
    • Principal Investigator: Grégoire Massoulié

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

Major patient eligible for an AF ablation procedure according to the recommendations (European Society of Cardiology 2020 and American Society of Cardiology 2014), either for symptomatic paroxysmal AF refractory to anti-arrhythmic treatments (or in first intention according to patient preference), or for symptomatic persistent AF.

Description

Inclusion Criteria:

• Adult patient, male or female, eligible for an AF ablation procedure according to the recommendations (European Society of Cardiology 2020 and American Society of Cardiology 2014), either for symptomatic paroxysmal AF refractory to anti-arrhythmic treatments (or in first intention according to patient preference), or for symptomatic persistent AF.
• Able to give their non-opposition to participate in the research.
• Affiliation to a social security regime.

Exclusion Criteria:

• Any pro-fibrotic phenomenon that may interfere with the interpretation of the results, i.e. severe valvular heart disease, amyloid heart disease, dilated cardiomyopathy of non-rhythmic origin, hypertrophic cardiomyopathy, severe ischaemic heart disease (late revascularisation, LV dysfunction, disturbed kinetics), COPD > stage 2, pulmonary fibrosis, renal failure > stage 3A, hepatic cirrhosis, hepatocellular failure, recent invasive surgery < 3 months
• Life expectancy less than 1 year
• Pregnant or breastfeeding women
• Patients of legal age under protective supervision (guardianship, trusteeship)
• Refusal to participate

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of an atrial fibrillation recurrence	ECG 12 lead profile	Any AF episode >30 seconds at pre-ablation (yes or no)
Occurrence of an atrial fibrillation recurrence	ECG 12 lead profile	Any AF episode >30 seconds at 3 months (yes or no)
Occurrence of an atrial fibrillation recurrence	ECG 12 lead profile	Any AF episode >30 seconds at 6 months (yes or no)
Occurrence of an atrial fibrillation recurrence	ECG 12 lead profile	Any AF episode >30 seconds at 12 months (yes or no)
Occurrence of an atrial fibrillation recurrence	Holter ECG	Any AF episode >30 seconds at pre-ablation (yes or no)
Occurrence of an atrial fibrillation recurrence	Holter ECG	Any AF episode >30 seconds at 3 months (yes or no)
Occurrence of an atrial fibrillation recurrence	Holter ECG	Any AF episode >30 seconds at 6 months (yes or no)
Occurrence of an atrial fibrillation recurrence	Holter ECG	Any AF episode >30 seconds at 12 months (yes or no)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	PIIINP at pre-ablation (in ng/mL
Occurrence of an atrial fibrillation recurrence	Biological markers profil	PIIINP at 12 months (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	ICTP at pre-ablation (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	ICTP at 12 months (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	PICP at pre-ablation (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	PICP at 12 months (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	sRAGE at pre-ablation (in pg/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	sRAGE at 12 months (in pg/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	AGE at pre-ablation (in ng/mL)
Occurrence of an atrial fibrillation recurrence	Biological markers profil	AGE at 12 months (in ng/mL)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of fibrosis of the left atrium	IRM profile	Degree of left atrial fibrosis on MRI at the inclusion (pre-ablation; in %)
Rate of fibrosis of the left atrium	Voltage mapping	Endocardial left atria low voltage area (<0.5mV) in sinus rhythm (in %)
Dominant frequency of AF	ECG 12 lead profil	F wave frequency at the inclusion (pre-ablation; in ms)
Dominant frequency of AF	ECG 12 lead profil	F wave frequency at 3 months (in ms)
Dominant frequency of AF	ECG 12 lead profil	F wave frequency at 6 months (in ms)
Dominant frequency of AF	ECG 12 lead profil	F wave frequency at 12 months (in ms)
Dominant frequency of AF	ECG 12 lead profil	F wave amplitude at the inclusion (pre-ablation; in mv)
Dominant frequency of AF	ECG 12 lead profil	F wave amplitude at 3 months (in mv)
Dominant frequency of AF	ECG 12 lead profil	F wave amplitude at 6 months (in mv)
Dominant frequency of AF	ECG 12 lead profil	F wave amplitude at 12 months (in mv)
Dominant frequency of AF	ECG 12 lead profil	AF characteristics at the inclusion (pre-ablation; paroxysmal, persistent)
Dominant frequency of AF	ECG 12 lead profil	AF characteristics at 3 months (paroxysmal, persistent)
Dominant frequency of AF	ECG 12 lead profil	AF characteristics at 6 months (paroxysmal, persistent)
Dominant frequency of AF	ECG 12 lead profil	AF characteristics at 12 months (paroxysmal, persistent)
Dominant frequency of AF	ECG 12 lead profil	AF duration at the inclusion (pre-ablation, in ms)
Dominant frequency of AF	ECG 12 lead profil	AF duration at 3 months (in ms)
Dominant frequency of AF	ECG 12 lead profil	AF duration at 6 months (in ms)
Dominant frequency of AF	ECG 12 lead profil	AF duration at 12 months (in ms)
Dominant frequency of AF	Holter ECG profil	F wave frequency at the inclusion (pre-ablation; in ms)
Dominant frequency of AF	Holter ECG profil	F wave frequency at 3 months (in ms)
Dominant frequency of AF	Holter ECG profil	F wave frequency at 6 months (in ms)
Dominant frequency of AF	Holter ECG profil	F wave frequency at 9 months (in ms)
Dominant frequency of AF	Holter ECG profil	F wave frequency at 12 months (in ms)
Dominant frequency of AF	Holter ECG profil	F wave amplitude at the inclusion (pre-ablation; in mV)
Dominant frequency of AF	Holter ECG profil	F wave amplitude at 3 months (in mV)
Dominant frequency of AF	Holter ECG profil	F wave frequency at 6 months (in mV)
Dominant frequency of AF	Holter ECG profil	F wave amplitude at 9 months (in mV)
Dominant frequency of AF	Holter ECG profil	F wave amplitude at 12 months (in mV)
Dominant frequency of AF	Holter ECG profil	AF characteristics at the inclusion (pre-ablation; paroxysmal, persistent)
Dominant frequency of AF	Holter ECG profil	AF characteristics at 3 months (paroxysmal, persistent)
Dominant frequency of AF	Holter ECG profil	AF characteristics at 6 months (paroxysmal, persistent)
Dominant frequency of AF	Holter ECG profil	AF characteristics at 9 months (paroxysmal, persistent)
Dominant frequency of AF	Holter ECG profil	AF characteristics at 12 months (paroxysmal, persistent)
Dominant frequency of AF	Holter ECG profil	AF duration at the inclusion (pre-ablation; in ms)
Dominant frequency of AF	Holter ECG profil	AF duration at 3 months (in ms)
Dominant frequency of AF	Holter ECG profil	AF duration at 6 months (in ms)
Dominant frequency of AF	Holter ECG profil	AF duration at 9 months (in ms)
Dominant frequency of AF	Holter ECG profil	AF duration at 12 months (in ms)
Dominant frequency of AF	Echocardiography	Left atria volume at pre-ablation (mL)
Dominant frequency of AF	Echocardiography	Left atria volume at 12 months (mL)
Dominant frequency of AF	Echocardiography	Indexed left atria volume at pre-ablation (mL)
Dominant frequency of AF	Echocardiography	Indexed left atria volume at 12 months (mL)
Dominant frequency of AF	Echocardiography	LVEF at the inclusion (pre-ablation; %)
Dominant frequency of AF	Echocardiography	LVEF at 12 months (%)
Dominant frequency of AF	Biological profil	Hemoglobin at pre-ablation (in g/dL)
Dominant frequency of AF	Biological profil	Hemoglobin at 12 months (in g/dL)
Dominant frequency of AF	Biological profil	HbA1c at pre-ablation (in %)
Dominant frequency of AF	Biological profil	HbA1c at 12 months (in %)
Dominant frequency of AF	Biological profil	Kalemia at pre-ablation (in mmol/L)
Dominant frequency of AF	Biological profil	Kalemia at 12 months (in mmol/L)
Dominant frequency of AF	Biological profil	Natremia at pre-ablation (in mmol/L)
Dominant frequency of AF	Biological profil	Natremia at 12 months (in mmol/L)
Dominant frequency of AF	Biological profil	Glycemia at pre-ablation (in mmol/L)
Dominant frequency of AF	Biological profil	Glycemia at 12 months (in mmol/L)
Dominant frequency of AF	Biological profil	Total bilirubin at pre-ablation (in µmol/L)
Dominant frequency of AF	Biological profil	Total bilirubin at 12 months (in µmol/L)
Dominant frequency of AF	Biological profil	ASAT at pre-ablation (in U/L)
Dominant frequency of AF	Biological profil	ASAT at 12 months (in U/L)
Dominant frequency of AF	Biological profil	ALAT at pre-ablation (in U/L)
Dominant frequency of AF	Biological profil	ALAT at 12 months (in U/L)
Dominant frequency of AF	Biological profil	GGT at pre-ablation (in U/L)
Dominant frequency of AF	Biological profil	GGT at 12 months (in U/L)
Dominant frequency of AF	Biological profil	PAL at pre-ablation (in U/L)
Dominant frequency of AF	Biological profil	PAL at 12 months (in U/L)
Dominant frequency of AF	Biological profil	LDH at pre-ablation (in U/L)
Dominant frequency of AF	Biological profil	LDH at 12 months (in U/L)
Dominant frequency of AF	Biological profil	Creatinine level at pre-ablation (in µmol/L)
Dominant frequency of AF	Biological profil	Creatinine level at 12 months (in µmol/L)
Dominant frequency of AF	Biological profil	Clearance CKD-EPI at pre-ablation (ml/min/1.73m²)
Dominant frequency of AF	Biological profil	Clearance CKD-EPI at 12 months (ml/min/1.73m²)
Dominant frequency of AF	Biological profil	Urea at pre-ablation (mmol/L)
Dominant frequency of AF	Biological profil	Urea at 12 months (mmol/L)
Dominant frequency of AF	Biological profil	Protidemia at pre-ablation (g/L)
Dominant frequency of AF	Biological profil	Protidemia at 12 months (g/L)
Dominant frequency of AF	Biological profil	NTproBNP at pre-ablation (ng/L)
Dominant frequency of AF	Biological profil	NTproBNP at 12 months (ng/L)
Dominant frequency of AF	Biological profil	TSH at pre-ablation (mUI/L)
Dominant frequency of AF	Biological profil	TSH at 12 months (mUI/L)
Dominant frequency of AF	Biological profil	T3 at pre-ablation (pmol/L)
Dominant frequency of AF	Biological profil	T3 at 12 months (pmol/L)
Dominant frequency of AF	Biological profil	T4 at pre-ablation (pmol/L)
Dominant frequency of AF	Biological profil	T4 at 12 months (pmol/L)
Dominant frequency of AF	Biological profil	Galectin-3 at pre-ablation (in ng/mL)
Dominant frequency of AF	Biological profil	Galectin-3 at 12 months (in ng/mL)
Dominant frequency of AF	Biological profil	sST2 at pre-ablation (in ng/mL)
Dominant frequency of AF	Biological profil	sST2 at 12 months (in ng/mL)
Dominant frequency of AF	Biological profil	miRNAs at pre-ablation (fold change)
Dominant frequency of AF	Biological profil	miRNAs at 12 months (fold change)
Dominant frequency of AF	Diabete profil	Diabete at pre-ablation (yes, type I, type II or no)
Dominant frequency of AF	Clinical exam	Body weight at pre-ablation (in kg)
Dominant frequency of AF	Clinical exam	Body weight at 3 months (in kg)
Dominant frequency of AF	Clinical exam	Body weight at 6 months (in kg)
Dominant frequency of AF	Clinical exam	Body weight at 12 months (in kg)
Dominant frequency of AF	Clinical exam	Body height at pre-ablation (in cm)
Dominant frequency of AF	Clinical exam	Body height at 3 months (in cm)
Dominant frequency of AF	Clinical exam	Body height at 6 months (in cm)
Dominant frequency of AF	Clinical exam	Body height at 12 months (in cm)
Dominant frequency of AF	Clinical exam	Systolic blood pressure at pre-ablation (in mmHg)
Dominant frequency of AF	Clinical exam	Systolic blood pressure at 3 months (in mmHg)
Dominant frequency of AF	Clinical exam	Systolic blood pressure at 6 months (in mmHg)
Dominant frequency of AF	Clinical exam	Systolic blood pressure at 12 months (in mmHg)
Dominant frequency of AF	Clinical exam	Diastolic blood pressure at pre-ablation (in mmHg)
Dominant frequency of AF	Clinical exam	Diastolic blood pressure at 3 months (in mmHg)
Dominant frequency of AF	Clinical exam	Diastolic blood pressure at 6 months (in mmHg)
Dominant frequency of AF	Clinical exam	Diastolic blood pressure at 12 months (in mmHg)
Dominant frequency of AF	Clinical exam	Cardiac frequency pressure at pre-ablation (in bpm)
Dominant frequency of AF	Clinical exam	Cardiac frequency pressure at 3 months (in bpm)
Dominant frequency of AF	Clinical exam	Cardiac frequency pressure at 6 months (in bpm)
Dominant frequency of AF	Clinical exam	Cardiac frequency pressure at 12 months (in bpm)
Dominant frequency of AF	Clinical exam	NYHA score at pre-ablation (I, II, III or IV)
Dominant frequency of AF	Clinical exam	NYHA score at 3 months (I, II, III or IV)
Dominant frequency of AF	Clinical exam	NYHA score at 6 months (I, II, III or IV)
Dominant frequency of AF	Clinical exam	NYHA score at 12 months (I, II, III or IV)
Dominant frequency of AF	Clinical exam	Congestive signs at pre-ablation (yes, left, right, global; or not)
Dominant frequency of AF	Clinical exam	Congestive signs at at 3 months (yes, left, right, global; or not)
Dominant frequency of AF	Clinical exam	Congestive signs at 6 months (yes, left, right, global; or not)
Dominant frequency of AF	Clinical exam	Congestive signs at 12 months (yes, left, right, global; or not)

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Groupama foundation; Biochemistry Lab University Hospital Clermont-Ferrand
• Investigators: Principal Investigator: Grégoire Massoulié, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: December 17, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: AF ablation; Atrial fibrillation (AF); Myocardial fibrosis; Biological collection; AF recurrence; AF and myocardial fibrosis biological markers
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Fibrosis; Atrial Fibrillation
• Other Study ID Numbers: RNI 2021 MASSOULIE; 2021-A02091-40 (Other Identifier: 2021-A02091-40)

Drug and device information, study documents

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