Intravascular Hemolysis Related to Pulsed Field Ablation

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EP LAB DIGEST. 2025;25(1):6.

Bradley P Knight, MD, FACC, FHRS

Dear Readers,

Pulsed field ablation (PFA) has become widely adopted in Europe and more recently in the United States and around the world as a nearly nonthermal energy source for cardiac ablation, particularly for catheter ablation of the pulmonary veins and left atrium for patients with atrial fibrillation (AF). Despite being more expensive, its adoption is being driven largely by its ease of use, efficiency, relative specificity for cardiac tissue, and the ability to avoid rare but severe complications such as left atrial esophageal fistula. Introduction of this new energy source and the associated electrode catheters designed to deliver PFA has come with the recognition of novel procedural risks and complications that were not considered in the past when using radiofrequency current or cryoenergy. One of these risks is intravascular hemolysis. Because delivery of PFA within the cardiac chambers when using particular catheter designs and waveforms can lyse red blood cells,1,2 hemolysis has been recognized as an issue that must be considered when performing these procedures. The problem with severe hemolysis is that it can cause acute kidney injury. Therefore, how many PFA shocks are too many? How many applications can cause clinically significant hemolysis and renal failure?

In October 2024, Stojadinović and colleagues published a study in the Journal of Cardiovascular Electrophysiology that investigated the issue of intravascular hemolysis during PFA in patients undergoing an AF ablation using the Farapulse (Boston Scientific) pentaspline catheter.3 The group performed catheter ablation procedures in 60 patients. The average age was 68 years, most were male, and the average serum creatinine was 91 micromoles per liter. Ablation beyond the pulmonary veins was performed in 73% of patients. Following an average of 74 applications, free hemoglobin (fHb), lactate dehydrogenase, and direct bilirubin significantly increased from a average of 40 to 493 mg/L, from 3.1 to 6.8 µkat/L, and from 12 to 28 µmol/L, respectively (all p < .0001). A strong linear correlation was found between the peak fHb and the number of PFA applications (R = 0.81, p < .001). Major hemolysis was defined as fHb >500 mg/L and was predicted by the number of PFA applications with the corresponding area under the receiver operating characteristic curve of 0.934. The optimum cut-off value of >74 PFA applications predicted major hemolysis with 89% sensitivity and 87% specificity. The authors determined that “the critical amount of pulsed electric field energy that may cause kidney injury in susceptible patients remains to be investigated.”

Based on this PFA study by Stojadinović et al and other obvervations, the following conclusions can be made about the relationship between PFA and hemolysis:
1. Red blood cells can hemolyze when exposed to a high voltage electric shock in the blood stream as occurs during PFA.

2. The degree of hemolysis is specific to the PFA catheter design, electrodes, and waveform.

3. Clinically significant intravascular hemolysis is rare, but in some patients can lead to acute kidney injury.

4. Acute kidney injury is probably underrecognized because post-ablation labs are not routinely measured in patients.

5. Patients should be instructed to notify their physician if they have notably dark urine post ablation.

6. Acute kidney injury is usually reversible and very rarely leads to an adverse outcome for the patient.

7. Efforts should be made to minimize the number of lesions during PFA ablation procedures for many reasons.

8. It is reasonable to avoid the delivery of more than 75 PFA applications when using the pentaspline PFA catheter to avoid significant hemolysis, unless it is felt that the additional lesions are worth the added risk in an individual patient.

9. Fewer than 75 applications with the Farapulse PFA system may still cause acute kidney injury in patients with underlying kidney disease.

10. Optimizing electrode contact with the cardiac tissue and avoiding floating electrodes are strategies to avoid major hemolysis.

11. Preprocedural intravenous hydration may avoid kidney injury from PFA-related hemolysis but can cause volume overload.

12. Other potential sources of acute kidney injury besides hemolysis include rhabdomyolysis from direct skeletal muscle stimulation and diaphragmatic contraction from phrenic nerve stimulation.

13. Future catheter designs should be developed to minimize the risk of intravascular hemolysis. 

Disclosures: Dr Knight has served as a paid consultant to Medtronic and was an investigator in the PULSED AF trial. In addition, he has served as a consultant, speaker, investigator, and/or has received EP fellowship grant support from Abbott, AltaThera, AtriCure, Baylis Medical, Biosense Webster, Biotronik, Boston Scientific, CVRx, Philips, and Sanofi; he has no equity or ownership in any of these companies.

References

1. Stewart MT, Haines DE, Miklavčič D, et al. Safety and chronic lesion characterization of pulsed field ablation in a porcine model. J Cardiovasc Electrophysiol. 2021;32(4):958-969. Epub 2021 Mar 10. doi:10.1111/jce.14980

2. Nies M, Koruth JS, Mlček M, et al. Hemolysis after pulsed field ablation: impact of lesion number and catheter-tissue contact. Círc Arrhythm Electrophysiol. 2024;17(6):e012765. Epub 2024 Apr 23. doi:10.1161/CIRCEP.124.012765

3. Stojadinović P, Ventrella N, Alfredova Ing H, et al. Prediction of major intravascular hemolysis during pulsed electric field ablation of atrial fibrillation using a pentaspline catheter. J Cardiovasc Electrophysiol. 2024 Oct 13. Online ahead of print. doi:10.1111/jce.16468