Advanced HF No Obstacle to AF Ablation Success: CASTLE-HTx

August 28, 2023

Catheter ablation had long taken atrial fibrillation (AF) rhythm control to the next level before clinical trials showed it could help keep AF patients with heart failure (HF) alive and out of the hospital.

But those trials didn't include many patients with AF on top of advanced or even end-stage HF. Lacking much of an evidence base and often viewed as too sick to gain a lot from the procedure, patients with AF and advanced HF aren't offered ablation very often.

Now a randomized trial suggests that, on the contrary, AF ablation may confer a similar benefit to patients with HF so advanced that they were referred for evaluation at a transplant center.

The study, modestly sized with fewer than 200 such patients and conducted at a single center, assigned half of them to receive ablation and the other half to continued medical management.

Risk for the composite primary endpoint plunged 76% over a median of 18 months for those who underwent ablation. The outcome comprised death from any cause, implantation of a left ventricular assist device (LVAD), or urgent heart transplantation.

The advantage for ablation emerged early enough that the trial, CASTLE-HTx, was halted for benefit only a year after reaching its planned enrollment, observed Christian Sohns, MD, when formally presenting the results August 27 in Amsterdam at the European Society of Cardiology (ESC) Congress 2023.

The difference in the primary endpoint "in this severely sick cohort of advanced, end-stage heart failure patients," he said, was driven mostly by fewer deaths, especially cardiovascular deaths, in the ablation group.

Ablation's effect on outcomes was associated, perhaps causally, with significant gains in left ventricular (LV) function and more than triple the reduction in AF burden seen in the control group, noted Sohns, from the Heart and Diabetes Center North-Rhine Westphalia, Bad Oeynhausen, Germany.

"Our trial suggests that in patients with atrial fibrillation and end-stage heart failure, catheter ablation may ameliorate the clinical course," states the CASTLE-HTx primary report, published in the New England Journal of Medicine, with Sohns as lead author, in tandem with his ESC presentation.

One of the study's key messages "is that AF ablation is safe and effective in patients with end-stage heart failure" and "should be part of our armamentarium" for treating them, said Philipp Sommer, MD, also with Heart and Diabetes Center North-Rhine Westphalia, at a press conference preceding Sohns' presentation of CASTLE-HTx.

The intervention could potentially help such patients survive longer on transplant wait lists and even delay need for the surgery, proposed Sommer, who is senior author on the trial's publication.

CASTLE-HTx suggests that patients with advanced HF and even persistent AF, "if they have reasonably small atria, should be actually considered for ablation, as it may prevent the need for heart transplant or LVAD implant," said invited discussant Finn Gustafsson, MD, PhD, DMSc, after Sohns' presentation. "And that, of course, would be a huge achievement."

The trial "should, if anything, help eradicate the current somewhat nihilistic approach to atrial fibrillation management in patients with advanced heart failure," said Gustafsson, medical director of cardiac transplantation and mechanical circulatory support, Rigshopsitalet Copenhagen University Hospital, Denmark.

Still, he disputed the characterization by the investigators and indeed the published report that the patients, or most of them, had "end-stage heart failure."

For example, about a third of the trial's patients started out in NYHA class 2, Gustafsson noted. Not that they weren't "high-risk" or their HF wasn't severe, he offered, but they don't seem to have been "a truly advanced heart failure population."

The trial population consisted of "patients referred to an advanced heart failure center, rather than patients with advanced heart failure," agreed Mandeep R. Mehra, MD, director of the Center for Advanced Heart Disease at Brigham and Woman's Hospital, Boston.

Also citing a large prevalence of patients in NYHA class-2, Mehra added that "we almost never see paroxysmal atrial fib in these patients. It's usually an early-stage phenomenon." In advanced HF, AF "is usually permanent," he told | Medscape Cardiology. Yet it was paroxysmal in about 30% of cases.

To its credit, Mehra observed, the study does assert that advanced HF is no reason, necessarily, to avoid catheter ablation. Nor should an AF patient's referral to an advanced-HF center "mean that you should rush to an LVAD or transplant" before considering ablation.

The study seems to be saying, "please exhaust all options before you biologically replace the heart or put in an LVAD," Mehra said. "Certainly, this paper steers you in that direction."

The trial entered 194 patients with symptomatic AF and HF of at least NYHA class 2, with impaired functional capacity by the 6-minute walk test, who had been referred to a major center in Germany for a heart-transplantation workup. With all on guideline-directed medical therapy, 97 were randomly assigned open-label to catheter ablation and 97 to continued standard care.

Catheter ablation was actually carried out in 81 patients (84%) who had been assigned to it and in 16 (16%) of those in the control group, the report states.

A total of 8 in the ablation group and 29 in the control arm died, received an LVAD, or went to urgent transplantation, for a hazard ratio (HR) of 0.24 (95% CI, 0.11 - 0.52, P < .001) for the primary endpoint.

Death from any cause apparently played a big role in the risk reduction; its HR was 0.29 (95% CI, 0.12 - 0.72).

One peculiarity of the data, Mehra said, is that event curves for the primary endpoint and its individual components "diverge almost from day 1." That would mean the ablation group right away started having fewer deaths, LVAD placements, or heart transplants than the control group.

"It is surprising to see such a large effect size on endpoints that are very much dependent on operators and diverge within the first day." Probably, Mehra said, "it has to do with this being a single-center study that may not be generalizable to other practices."

CASTLE HTx was supported by a grant from Else Kröner-Fresenius-Stiftung. Sommer discloses consulting for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Sohns reported no relevant financial relationships. Gustafsson discloses receiving honoraria or fees for consulting from Abbott, Alnylam Amgen, Boehringer Ingelheim, Ionis, Novartis, and Pfizer; serving on a speakers bureau for Astra Zeneca and Orion; and receiving grants from Corvia Research. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board for NuPulseCV, Leviticus, and FineHeart.

European Society of Cardiology Congress 2023, Hot Line 6
Presented August 27, 2023.

N Engl J Med. Published online August 27, 2023. Abstract

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