Some Degree of Hemolysis Seen in Nearly All Pulsed-Field Ablation Cases

BERLIN, Germany—Evidence of hemolysis was detected in the vast majority of patients undergoing pulsed-field ablation (PFA) for atrial fibrillation (AF) in a prospective study conducted at four European centers, although the clinical relevance is uncertain.

There were significant changes in mean levels of free plasma hemoglobin, haptoglobin, and bilirubin indicative of hemolysis after PFA, but similar changes were not seen among patients treated with radiofrequency ablation, according to Miruna-Andreea Popa, MD (Hôpital Cardiologique du Haut-Lévêque, CHU de Bordeaux, Pessac, France).

The severity of hemolysis correlated with the number of PFA applications, with the most-substantial changes in biomarkers observed above a threshold of 54 energy deliveries, Popa reported here at the European Heart Rhythm Association Congress 2024. “So the more PFA deliveries we apply, the more hemolysis we will have.”

It’s not clear whether the hemolysis related to PFA has serious clinical consequences. There were no significant cases of anemia recorded, and no mean changes in glomerular filtration rate (GFR). Four patients developed acute kidney injury during the study, all after PFA, but a definitive link to hemolysis could not be established.

Ultimately, Popa said, additional studies on the impact of PFA-induced hemolysis are needed. “Until we have those data, we should consider whether we should titrate our PFA deliveries.”

Assessing PFA-Related Hemolysis

PFA has emerged in recent years as an alternative to thermal ablation with radiofrequency or cryoballoon catheters. One of the big selling points for the newer modality, along with faster procedural times, is enhanced safety. PFA works through electroporation, which is believed to lessen the potential for damage to structures surrounding the heart, like the esophagus and phrenic nerve.

Red blood cells have been shown in prior research to be susceptible to electroporation, but there is little evidence on PFA’s possible impact on hemolysis.

To take a closer look, Popa and her colleagues performed a prospective, observational study of 187 consecutive patients (mean age 65.5 years; 72.7% men) who underwent catheter ablation for paroxysmal or persistent AF at four high-volume centers in Europe. The study included 145 patients who underwent PFA with a pentaspline catheter and 42 who underwent radiofrequency ablation with an irrigated-tip catheter. PFA involved an average of 61.4 energy deliveries, and the mean radiofrequency duration was 31.0 minutes.

Blood samples were taken at least 24 hours before the procedure, at the end of ablation, and 1 day after the procedure to assess levels of biomarkers indicative of hemolysis, renal function, and anemia.

Hemolysis was detected in 94.3% patients who underwent PFA. Mean free plasma hemoglobin levels significantly increased from before to immediately after ablation, although levels came back down by 24 hours after the procedure. At the same time, there was a significant decrease in levels of haptoglobin and a significant increase in bilirubin (P < 0.001 for all changes). Signs of hemolysis were not observed in the radiofrequency-ablation group.

In exploring the potential clinical impact of these findings, the investigators found that anemia and renal function were similar in the PFA and radiofrequency-ablation groups, with a slight decline in hemoglobin and no significant changes in GFR or creatinine levels irrespective of ablation type.

Of the four patients who developed acute kidney injury following PFA, three had acute urinary retention, “which poses the question whether hemolysis was indeed causal for acute kidney injury in this case or not,” Popa said. She noted, however, that hemoglobinuria was seen in 36% of PFA cases, “which may raise the concern of a potential nephrotoxic effect.”

Something to Keep an Eye On

Gregory Michaud, MD (Massachusetts General Hospital, Boston), one of the chairs of the moderated poster session at which Popa presented the results, asked Popa whether these data have changed how she approaches PFA.

Hemolysis is not the only factor that should be considered when thinking about limiting PFA deliveries, she responded. “Because it’s fast and probably safe doesn’t mean that we should do extensive ablation of the left atrium,” Popa said, noting that she is using PFA mostly for pulmonary vein isolation alone in paroxysmal AF cases.

Serious consequences of hemolysis seem to be rare. In the single-arm PULSED AF trial of the PulseSelect PFA system (Medtronic), there were no renal adverse events reported. And in the ADVENT trial pitting the Farapulse PFA system (Boston Scientific) against thermal ablation, there was just one procedure-related renal event (in the PFA arm) and five renal adverse events overall (three with PFA and two with thermal ablation).

Looking at a much larger number of patients treated with PFA, however, investigators from the MANIFEST-17K study uncovered some issues related to hemolysis. Among more than 17,000 patients treated in Europe after CE Mark approval of the Farawave catheter, part of the Farapulse system, five (0.03%) developed hemolysis-related renal failure requiring hospitalization and transient dialysis, with a sixth affected patient managed without hospitalization. All of the hospitalized patients had persistent AF and received a high number of PFA lesions during their procedures (an average of 143), and all had normalized renal function at follow-up.

Vivek Reddy, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who presented those data American Heart Association 2023 Scientific Sessions, noted at the time that this complication is easily manageable by limiting the number of lesions placed and using saline hydration.

Speaking with TCTMD, Michaud said PFA-related hemolysis is “a real thing” that has been reported in multiple publications now, indicating, however, that there’s still a lot to learn about it.

Reflecting on the available data on serious events related hemolysis after PFA, he said, “I’m not that concerned really.” He pointed to the rarity of the complication, adding, however, that “you still worry about the rare things even though they don’t happen that frequently. So we need to understand a little bit more. Obviously, we’re in the relative infancy of all of this, [but] it’s not changing what I’m doing right now.”

For now, Michaud said, the take-home message is that doing an “indiscriminate number of lesions is probably not a good idea. It’s not clear that that is necessary, first of all. And second, at least in the early stages, we should probably be screening these people [postprocedure], as we’re doing, to make sure that there aren’t some patients that are going to come back with—even if it’s temporary—renal failure.”