Renal Function and Hemolysis After Pulsed-field Ablation for Atrial Fibrillation

The Assessment of Hemolysis and Renal Functions During and After Catheter Ablation for Atrial Fibrillation Using Pulsed-field Energy

The aim of the project is to assess hemolysis and renal function after catheter ablation for atrial fibrillation using pulsed-field energy. Hemolysis will be determined using the concentration of red blood cell microparticles at the end of the ablation (when all ablation were done, before sheath removal). Hemoglobinuria will be assessed one day after the procedure. Renal functions will be assessed one and three day after the procedure using standard parameters (creatinine, urea). The goal is to assses the acute worsening fo renal functions after pulsed-field ablation in relation to the number of PF applications, and to the degree of immediate post-procedural hemolysis.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: Pulsed-field ablation

Detailed Description

Methods The project will include patients with paroxysmal and persistent AF who, according to standard recommended procedures, are indicated for catheter ablation using pulsed-field energy and will sign informed consent. Patients with spontaneously present hemolysis (hematologic disorders) and patients in a dialysis program will be excluded. The catheterization procedure will be performed routinely as currently practiced at our institution. Specifically, pulmonary vein isolation will be conducted in all patients, and for patients with non-paroxysmal AF, additional additive ablation lesions will also be performed (most commonly ablation of the posterior wall of the left atrium and mitral isthmus, possibly the cavotricuspid isthmus). The ablation will always be performed under moderate sedation or general anesthesia with the participation of an anesthesiologist, as per our institution's practice. A total of 100 patients are planned to be enrolled. Prior to the procedure, patients will receive at least 4 weeks of anticoagulant treatment with NOACs, as recommended, and this treatment will be discontinued on the day of the procedure (i.e., the last tablet will be taken the day before the procedure). NOACs will be reintroduced into their medication regimen the day after ablation. All patients will undergo outpatient baseline blood tests, including renal function (creatinine, urea), as currently standard and required (up to 2 weeks before the procedure). Post-procedure, patients will be adequately hydrated; in addition to the recommended active oral intake post-procedure, all patients will receive an extra 1000 ml of saline solution during the afternoon following the procedure (unless there is a risk of overhydration, for instance, in the case of severe dysfunction).

Blood sampling Blood samples will be collected at two different times. Firstly, at the end of the procedure, 12 ml of blood will be drawn into tubes for hemolysis examination (anticoagulated blood with EDTA and Li-heparin). The degree of hemolysis will be assessed by examining red blood cell fragments (RBC microparticles) using flow cytometry. This examination is highly sensitive and capable of detecting even minimal amounts of damaged erythrocytes. The second blood sample will be collected the morning after the procedure, following the standard protocol, and will also include renal parameters (creatinine, urea) as routinely done. Additionally, on this day, a urine test for the presence of hemoglobinuria will be conducted. Both initial blood samples will be collected and analyzed during the hospitalization. A third sample for a follow-up assessment of kidney function will be required 2-3 days after the procedure. The patient will be asked to come either to our hospital for blood collection or to have it done at a laboratory near their residence. Results of this examination, if conducted outside the hospital, will be obtained from the patient over the phone. If kidney function in this sample is slightly reduced, the patient will be instructed for further monitoring or outpatient examination. In case of significantly elevated values, appropriate action will be advised promptly.

Three months post-procedure, an outpatient check-up will be conducted. Before this evaluation, the effectiveness of the ablation will be assessed using a 24-hour ECG Holter monitor, which is our current standard procedure. Additionally, kidney function will be rechecked. The purpose is to compare the number of applications of pulsed-field energy with the degree of hemolysis observed immediately after the procedure, along with kidney function shortly after. Hemolysis, the damage or breakdown of red blood cells, will be determined using a highly sensitive method and is practically certain to be present at the end of the procedure. However, whether hemolysis might lead to hemoglobinuria the following day in some cases has not been investigated, nor has the potential for temporary worsening of kidney function in certain patients. If this were the case, selecting at-risk patients (those with higher creatinine levels before the procedure) and implementing simple measures (sufficient fluid intake) could effectively prevent this complication. Our primary hypothesis is that while ablation using pulsed-field is associated with intravascular hemolysis, leading to the damage of some red blood cells, this process in only a minimal number of patients will result in hemoglobinuria, and it will not have any significant consequences on kidney function post-procedure.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 10034
    • Cardiocenter, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patient will symptomatic paroxysmal or non-paroxysmal atrial fibrillation indicated for catheter ablation according to the standard criteria will be enrolled.

Description

Inclusion Criteria:

• symptomatic paroxysmal or non-paroxysmal atrial fibrillation

Exclusion Criteria:

• known hematologic disoders
• disorders associated with increased hemolysis
• known significant hepatic disease
• patient in permanent hemodialysis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulsed-field ablation group; Patient with atrial fibrillation will undergo catheter ablation using pulsed-field energy	Device: Pulsed-field ablation; Patients will atrial fibrillation will undergo catheter ablation using pulsed-field energy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red blood cell microparticles	The concentration of red blood cell microparticles in the plasma assessed using flow cytometry	day of the procedure - at the end of the procedure
Hemoglobinuria	The concentration of hemoglobin in urine	One day after the procedure
Creatinine three days	The cooncentration of creatinine three days after ablation	3 days after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate dehydrogenase	The concentration of lactate dehydrogenase at the end of ablation	the day of the procedure - at the end of the procedure
Haptoglobin	The concentration of haptoglobin at the end of ablation	the day of the procedure - at the end of the procedure
Creatinine one day	The concentration of creatinine one day after ablation	one day after the procedure

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic

Publications and helpful links

General Publications

• Reddy VY, Dukkipati SR, Neuzil P, Anic A, Petru J, Funasako M, Cochet H, Minami K, Breskovic T, Sikiric I, Sediva L, Chovanec M, Koruth J, Jais P. Pulsed Field Ablation of Paroxysmal Atrial Fibrillation: 1-Year Outcomes of IMPULSE, PEFCAT, and PEFCAT II. JACC Clin Electrophysiol. 2021 May;7(5):614-627. doi: 10.1016/j.jacep.2021.02.014. Epub 2021 Apr 28.
• Zoni-Berisso M, Filippi A, Landolina M, Brignoli O, D'Ambrosio G, Maglia G, Grimaldi M, Ermini G. Frequency, patient characteristics, treatment strategies, and resource usage of atrial fibrillation (from the Italian Survey of Atrial Fibrillation Management [ISAF] study). Am J Cardiol. 2013 Mar 1;111(5):705-11. doi: 10.1016/j.amjcard.2012.11.026. Epub 2012 Dec 28.
• Wolf PA, Benjamin EJ, Belanger AJ, Kannel WB, Levy D, D'Agostino RB. Secular trends in the prevalence of atrial fibrillation: The Framingham Study. Am Heart J. 1996 Apr;131(4):790-5. doi: 10.1016/s0002-8703(96)90288-4. No abstract available.
• Ekanem E, Reddy VY, Schmidt B, Reichlin T, Neven K, Metzner A, Hansen J, Blaauw Y, Maury P, Arentz T, Sommer P, Anic A, Anselme F, Boveda S, Deneke T, Willems S, van der Voort P, Tilz R, Funasako M, Scherr D, Wakili R, Steven D, Kautzner J, Vijgen J, Jais P, Petru J, Chun J, Roten L, Futing A, Rillig A, Mulder BA, Johannessen A, Rollin A, Lehrmann H, Sohns C, Jurisic Z, Savoure A, Combes S, Nentwich K, Gunawardene M, Ouss A, Kirstein B, Manninger M, Bohnen JE, Sultan A, Peichl P, Koopman P, Derval N, Turagam MK, Neuzil P; MANIFEST-PF Cooperative. Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF). Europace. 2022 Sep 1;24(8):1256-1266. doi: 10.1093/europace/euac050. Erratum In: Europace. 2023 Feb 16;25(2):449.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): July 30, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: atrial fibrillation; renal function; hemolysis; pulsed-fied ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hemolysis
• Other Study ID Numbers: PFA RENAL HEMOLYSIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be shared 6 months after publication on request.

Drug and device information, study documents

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