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\begin{document}

\title{In which patients with heart failure should ablation of atrial
fibrillation not be performed?}



\author[1]{Hitoshi Hachiya}%
\affil[1]{Tsuchiura Kyodo Hospital}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\selectlanguage{english}
\begin{abstract}
Catheter ablation of atrial fibrillation (AF) in patients with heart
failure associated with a reduced EF (HFrEF) was associated with a
significantly lower rate of a composite endpoint of death from any cause
or hospitalization for worsening heart failure (HF) than medical therapy
in the CASTLE-AF trial. In patients with HF and also with a preserved EF
(HFpEF), AF is known to be associated with increased mortality. Although
the particular benefit in patients with an EF \textgreater{}35\% may
suggest the need for prospective randomized control trial data in
patients with HF to assess the role of ablation as a first-line therapy
as Sessions AJ, et al. stated, we believe at present that 1) whether
there is structural heart disease detected by cardiac images and 2)
whether the left atrial voltage is generally low, should be assessed
``before ablation'' in each patient with HF to achieve a successful
ablation.%
\end{abstract}%



\sloppy


\textbf{In which patients with heart failure should ablation of atrial
fibrillation not be performed?}

Hitoshi Hachiya,

Tsuchiura Kyodo General Hospital, Cardiology Department

\textbf{Introduction}

Many ablation strategies and techniques have been proposed since
pulmonary vein (PV) ostial isolation to eliminate atrial fibrillation
(AF) triggers was introduced in 2000. Circumferential PV ablation, PV
antrum isolation (PVAI),\textsuperscript{1} and extensive PV isolation
(EPVI)\textsuperscript{2,3} have been performed widely as the principal
procedures because they have attained high cure rates with an acceptable
safety.\begin{CJK}{UTF8}{gbsn}\textsuperscript{3　}\end{CJK}\selectlanguage{english}Further, recently, some clinical trials have
compared the effects of catheter ablation and rhythm control with
medical therapy in patients with AF-associated heart failure (HF).

\textbf{Ablation vs. Medical therapy in patients with AF and heart
failure}

The AATAC (Ablation vs. Amiodarone for Treatment of Persistent Atrial
Fibrillation in Patients with Congestive Heart Failure and an Implanted
ICD/CRT-D) trial compared the effect of catheter ablation and rhythm
control with amiodarone in patients with AF-associated HF and showed
that the sinus rhythm maintenance rate after ablation was significantly
higher than after amiodarone therapy (70\% vs. 34\%), resulting in
significant improvements in the QOL and mortality
rates.\textsuperscript{4} Regarding the catheter ablation of AF with
heart failure, in addition, Marrouche NF, et al. published in N Engl J
Med 2018 that it was associated with a significantly lower rate of a
composite end point of death from any cause or hospitalization for
worsening HF than was medical therapy.\textsuperscript{5} In the
CASTLE-AF trial, patients were included if they had paroxysmal or
persistent AF, a New York Heart Association (NYHA) class II, III, or IV
heart failure, and a left ventricular ejection fraction (LVEF) of 35\%
or less. That is, patients with HF with a reduced EF (HFrEF) were
selected in the CASTLE-AF trial. In patients with HF and HFrEF with
persistent symptoms despite medical therapy, catheter ablation (CA) is
associated with a decreased all-cause mortality, decreased rates of
cardiovascular hospitalizations, and lower rates of recurrence as
compared to medical therapy.\textsuperscript{6} In the manuscript
published by Sessions AJ, et al.\textsuperscript{7}, the patients were
examined according to their ejection fraction (EF): EF [?]35\% (n = 1024)
and EF \textgreater{}35\% (n=8955). They stated that mainly delaying
treatment of AF with catheter ablation in patients with concurrent left
ventricular dysfunction resulted in an increased all-cause mortality in
all patients and significantly increased HF hospitalizations, strokes,
and AF recurrence in patients with an EF \textgreater{}35\%.
Additionally, in patients with an EF [?]35\%, it was written that a delay
in performing catheter ablation impacted the outcomes, in particular the
mortality risk. In the EF [?]35\% group, catheter ablation did not impact
the stroke rates with early use, however, the stroke event rates were
low in this population. Those data in aggregate favor the early use of
ablation of AF in patients with HF. Without touching on the early use of
ablation of AF in patients with HF, the JCS guidelines determine that
catheter ablation therapy in AF patients with HF is an option that can
be expected to improve the prognosis and recommends applying the same
indication level with or without HF on the basis of some study results
at this time.\textsuperscript{8}

\textbf{A case in which ablation was refractory?}

Here, I am concerned about which patients with heart failure should an
ablation of AF not be performed. In our institution's cases, there were
low-voltage areas in the anterior left atrium (LA) (Figure) in a patient
with persistent AF and an EF of 24\%. We performed an EPVI in the
1\textsuperscript{st} procedure and created mitral isthmus block with a
chemical ablation and performed an isolation of the posterior LA wall in
the 2\textsuperscript{nd} procedure 7 days after the
1\textsuperscript{st} procedure. However, atrial tachycardia emerged
after the EPVI and the HF did not improve. Therefore, the patient
started taking amiodarone 200mg/day to maintain sinus rhythm (SR), and
cardiac re-synchronized therapy (CRT) was performed. If the atrial
tachycardia were to recur, we might have to perform an atrio-ventricular
junctional (AVJ) ablation. We wonder whether an EPVI should be performed
in this patient if an AVJ ablation must be performed.

\textbf{Impact of the degree of LV dysfunction}

AF is known to be associated with increased mortality only in patients
with HF with a preserved EF (HFpEF), defined as the presence of signs
and symptoms of HF with an EF of
\textgreater{}50\%.\textsuperscript{9}In our report,\textsuperscript{10}
a total of 106 consecutive HF patients, including 51 (48.1\%) with a
reduced left ventricular ejection fraction (LVEF) (HFrEF) and 55
(51.9\%) with a preserved LVEF (HFpEF), underwent AF ablation. All
patients underwent a successful PVAI, and substrate modification was
added in 38 (35.8\%). In the patients with HFrEF, normalization of the
LVEF (LVEF [?] 50\%) was observed in 37 (72.5\%) patients during the
follow-up period. Multivariate logistic analyses revealed that a smaller
left ventricular end-diastolic diameter (LVDd) was the sole parameter
predicting an LVEF normalization post-procedure (odds ratio {[}OR{]} =
0.863; 95\% confidence interval {[}CI{]} = 0.779--0.955, p = 0.005). For
the association between the LVDd and LVEF normalization post-procedure,
the area under curve (AUC) of 0.774 (95\% CI = 0.618--0.930) was
observed. The optimal cut-off point for the LVDd for predicting an LVEF
normalization post-procedure was 53.5 mm (sensitivity 64.9\%,
specificity 78.6\%). Interestingly, in the CASTLE-AF trial, there was a
significant interaction between the left ventricular ejection fraction
(LVEF) and primary endpoint (death from any cause or admission for
worsening heart failure), which implies that patients with an LVEF of
25\% or more are more likely to have a benefit from ablation of AF than
those with an LVEF of less than 25\%.\textsuperscript{5}

\textbf{Bipolar vs. Unipolar voltage mapping of AF ablation}

We are contemplating the utility of the unipolar electrogram for
assessing low-voltage areas. The result may help to judge how we should
perform AF ablation, especially in patients with HF. Ablation of
low-voltage areas in the left atrium (LA) has been reported as having
therapeutic value for maintaining sinus rhythm.\textsuperscript{11} On
the other hand, bipolar voltage criteria may be affected both by the
activation direction of the superficial atrial activation and by
insufficient contact with the endocardial tissue. There may also be
differences in the visibility due to specific features of the mapping
catheter (i.e., size of the electrodes, distance between the electrodes,
etc.). In the near future, advanced atrial remodeling evaluated by
unipolar electrograms (Figure) may show an important cause of atrial
arrhythmias.

\textbf{Cardiac magnetic resonance imaging}

Prabhu S, et al. published the following study in J Am Coll Cardiol,
2017.\textsuperscript{12} This multicenter, randomized clinical trial
enrolled patients with persistent AF and idiopathic cardiomyopathy (left
ventricular ejection fraction {[}LVEF{]}[?]45\%). After optimization of
the rate control, the patients underwent cardiac magnetic resonance
(CMR) imaging to assess the LVEF and late gadolinium enhancement,
indicative of ventricular fibrosis, before randomization to either
catheter ablation (CA) or ongoing medical rate control (MRC). A total of
301 patients were screened; 68 patients were randomized with 33 in each
arm. The average AF burden post-CA was 1.6 \selectlanguage{ngerman}± 5.0\% at 6 months. In the
intention-to-treat analysis, the absolute LVEF improved by 18 ± 13\% in
the CA group as compared to 4.4 ± 13\% in the MRC group (p \textless{}
0.0001) and normalized (LVEF \selectlanguage{english}[?]50\%) in 58\% versus 9\% (p = 0.0002). In
those undergoing CA, the absence of late gadolinium enhancement
predicted greater improvements in the absolute LVEF (10.7\%; p = 0.0069)
and normalization at 6 months (73\% vs. 29\%; p = 0.0093).

\textbf{Summary}

Although Sessions AJ, et al. \textsuperscript{7} stated that of course,
the particular benefit in patients with an EF \textgreater{}35\%
suggests the need for prospective randomized control trial data in
patients with HF to assess the role of ablation as a first-line therapy,
we believe at present that 1) whether there is structural heart disease
detected by cardiac MRI\textsuperscript{12} or scintigraphy and 2)
whether the left atrial voltage is generally low, should be assessed
``before ablation'' in each patient with HF to achieve a successful
ablation.

\textbf{References}

\begin{enumerate}
\tightlist
\item
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\item
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\item
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\end{enumerate}

\textbf{Figure legend}

The 3D view of the anterior left atrium with bipolar voltage mapping (A)
and unipolar voltage mapping (B) with an~\textbf{OCTARAY} \selectlanguage{english} mapping
catheter after the EPVI. The red area is \selectlanguage{english}[?]0.05 mV.\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}The cut-off value in
both A and B was 0.05mV~0.5mV. The real low voltage area may be
detected by the unipolar rather than the bipolar mapping.\selectlanguage{english}
\begin{figure}[H]
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