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\begin{document}

\title{Aggressive Treatment of Atrial Fibrillation in Hypertrophic
Cardiomyopathy Patients Improve Quality of Life}



\author[1]{Gerald Naccarelli}%
\author[2]{Eric Popjes}%
\affil[1]{Penn State Health Milton S Hershey Medical Center}%
\affil[2]{Penn State College of Medicine}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\textbf{Aggressive Treatment of Atrial Fibrillation in Hypertrophic
Cardiomyopathy}

\textbf{Patients Improve Quality of Life}

Gerald V. Naccarelli MD

Eric D. Popjes MD

From: Penn State University College of Medicine

Penn State Health

Penn State Heart and Vascular Institute.

The Milton S. Hershey Medical Center

Hershey, Pa, USA

Running Title: Atrial Fibrillation and Hypertrophic Cardiomyopathy

Key Words: Antiarrhythmic Drugs; Atrial Fibrillation; Hypertrophic
Cardiomyopathy;

Quality of Life

Total Word Count: Editorial (1276) and with references (1911)

Corresponding Author:

Gerald V. Naccarelli MD

Penn State University College of Medicine

Penn State Hershey Heart \& Vascular Institute

500 University Drive, Room H1511

Hershey PA 17033

Phone: 1-717-531-3907

Fax: 1-717-531-4077

gnaccarelli@penntatehealth.psu.edu

Potential Conflicts; Gerald V. Naccarelli MD (Consultant: Milestone,
Sanofi, In Cardia Therapeutics, Acesion, Glaxo Smith Kline); Eric Popjes
MD (none)

Hypertrophic cardiomyopathy (HCM) is a common inherited disease
occurring in about 1 of 500 births. Atrial fibrillation (AF) is the most
commonly occurring tachyarrhythmia and often occurs in patients with
structural heart disease. Thus, it is not surprising that AF occurs in
about 25\% of patients with HCM and is likely to occur due to changes in
atrial histology including myocyte hypertrophy and disarray,
interstitial fibrosis and left atrial dilatation secondary to left
ventricular hypertrophy, outflow obstruction and mitral regurgitation
(1,2). AF can lead to rapid rates, the loss of an atrial contribution to
cardiac output and shortening of diastolic filling time that can lead to
increased left ventricular filling pressures and significant hemodynamic
symptoms and heart failure in HCM patients. In addition, stroke rates
increase eight-fold when these two diseases co-exist independent of any
risk score. The HCM guideline (3) states that a principal goal of
treating patients with symptomatic HCM is to improve their symptoms and
their overall function and quality of life (QOL). Based on these facts
and previous research, the presence of concomitant AF with HCM are of
major concern related to prognostic and QOL indicators.

In this edition of the Journal of Cardiovascular Electrophysiology,
Rowin et al report on the QOL in fifty patients who had HCM and AF at
one major HCM center (4). These patients came from a cohort of 218
consecutive patients with HCM who filled out patient reported outcome
measures. The investigators used the Kansas City Cardiomyopathy
Questionnaire (KCCCQ)(5) in all HCM patients and the Atrial Fibrillation
Effect on Quality of Life (AFEQT)(6) in the AF cohort. Patients had AF
for a median of 5.5 years prior to the study survey. Of note, 66\% of
patients were treated with a rhythm control strategy and the remainder a
rate control strategy utilizing beta-blockers and calcium blockers. The
AFEQT reported that 52\% of patients experienced no or minimal
AF-related disability with 22\% describing mild to moderate and 26\%
severe issues. There was no difference based on HCM phenotype. After
treatment, the presence of AF did not impact QOL in these patients.
Using the KCCQ-OS score heart failure symptoms were similar with 59\%
having no or minimal symptoms. Surprisingly, a history of concomitant AF
was associated with less HF symptoms and improved QOL.

The results of this study need to be put into clinical perspective. This
trial was a retrospective analysis and there was no prospective,
controlled randomization of treatments. Patients were treated at a major
HCM center with expertise in using guideline management, including
anticoagulation and aggressive use of rhythm control strategies
including antiarrhythmic drugs and catheter ablation (3,7). Of the fifty
patients, 70\% had obstructive HCM and seventeen patients had prior
surgical myectomy and four patients had alcohol septal ablation.
Two-thirds of the AF patients had rhythm control attempts including
one-third with catheter ablations procedures and ten patients (20\%) had
MAZE procedures at the time of their myectomy and only six patients were
treated with sotalol or amiodarone. The remaining AF patients were
treated using just rate control drugs. From a HCM perspective the
severity of baseline disease and obstructive physiology is validated by
the fact that twenty-one of the patients had either a septal or alcohol
myectomy. A prior study showed that 80\% of patients who had septal
myectomy had over a 20-point improvement in their KCCQ score (8).
Although this group of patients were sicker and referred to a major HCM
center, we would caution extrapolating these findings to HCM patients
with AF who may not require aggressive management. This population does
not represent the bell-shaped curve of all patients with HCM cared for
in a routine cardiologist's practice.

Even though prior to treatment this group may have had more advanced HCM
disease, 75\% had mild to moderate QOL scores. This paper only reports
on QOL measure from the most recent clinic visit. Patients did not have
baseline QOL measures that obviously improved at the time of these QOL
surveys post aggressive treatment. In addition, all QOL measures are
limited and using two different QOL surveys in the same group of
patients may limit the findings of this study. In addition, QOL data was
collected at a single point in time and thus treatment effect size could
not be determined. This limitation could have been minimized by
collecting data over a longer time. Clinically meaningful treatment
effects have been controversial using QOL survey tools; although, Holmes
et al, using the ORBIT-AF registry, defined a plus or minus 5-point
change as clinically meaningful for AF patients (9). AF history averaged
5.5 years prior to the QOL surveys, and most patients did not have AF
recurrence in the month before the survey.

The authors are major experts in the care of such patients and the
results may not be extrapolated to other caretakers with less
experience. Patients were offered anticoagulation in this trial
consistent with guideline recommendations (3,7) independent of
CHA2Ds2-VASc score given the fact that HCM patients with AF have an
embolic risk like those with a CHA2Ds2-VASc score of 3. This is a
practice we follow at our own center.

The data suggests that minimizing AF recurrences improves and reverses
heart failure symptoms in these patients given most patients in this
study had paroxysmal AF and only four patients had permanent AF. To no
surprise the patients with the most frequent AF recurrences had more
symptoms and worse QOL scores. Younger patients with a high number of AF
recurrences had worse reported AF disability and patients with less
episodes reported less disability. This finding supports the aggressive
rhythm strategies used by these investigators including the fact that HF
symptoms improve upon controlling AF in such patients. The CABANA trial,
in a patient population without HCM, previously reported the benefits of
catheter ablation over antiarrhythmic drugs in a large AF population in
improving QOL using the AFEQT score (10). The high use of ablation for
the AF patients may have affected the results but also suggests
aggressive management of HCM with AF should be instituted earlier given
the concerns of the safety and less efficacy of antiarrhythmic drugs in
this patient population. Using catheter ablation for AF in such patients
is supported by the recent data from Castagno et al (11) who reported
that catheter ablation was effective in controlling AF in 61\% of 111
patients with 6 years follow-up; although on average, patients required
1.6 ablations to achieve this efficacy.

This report represents a small population that limits sub-analyses
although the authors did their best given this major limitation. There
are cohorts of HCM patients that may have QOL issues such as those with
pulmonary hypertension (12) who might benefit from specific forms of
therapy that could not be analyzed given the small sample size. Further
large prospective studies in patients with HCM and AF should be
performed measuring QOL measure before and after treatments in a
longitudinal fashion so that the best management of these patients can
be determined. New treatments for HCM and AF will continue to be a
moving target. Mavacamten, a new cardiac myosin inhibitor treatment for
HCM, improved KCCQ overall scores compared to placebo in patients with
symptomatic, obstructive HCM and this difference returned to baseline
after discontinuation of the active treatment (13). Data from the
present trial was collected before large scale use of this treatment was
available. Obviously, similar studies cannot be performed for
irreversible treatments such as catheter ablation of AF or septal
myectomy. In the meantime, data from this study suggests that current
treatment strategies are effective and aggressive management of both
their HCM and AF is useful in making these patients happy and enjoying
their QOL.

\textbf{References}

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