Risk factors for the development of AF and detection in HCM

Studies have described multiple clinical, electrocardiogram (ECG), and echocardiogram (ECHO) features
as independent FACTORS of AF in HCM patients. Left atrial diameter, age, and heart failure class are the
strongest independent predictors of the development of AF.

There was no uniformly unfavorable long-term outcome for AF patients, and about one third of them
had an uneventful course, particularly if their condition did not progress to chronic AF .The
anteroposterior diameter of the left atrium > 45 mm has been the most widely accepted size for
predicting AF risk in HCM patients. 7381 patients (33 studies) participated in a meta-analysis in which
the LA diameter was 38 mm in patients with sinus rhythm, compared to 45 mm in those with AF.
According to a study of 480 patients, LA diameter > 45 mm was significantly associated with an
increased risk of AF, and this is recommended in the guidelines, study examined the prognostic
implications of AF in a large, community-based HCM population compiled from Italian and US cohorts.
[47,48].

With age, HCM patients are more likely to have AF than age-matched cohorts; however, AF rarely occurs
in those with HCM who are 30 years or younger and becomes more frequent with age,According to the
American guidelines, 24-hour ambulatory ECG monitoring can be considered in adults with a
hypertrophied left atrium to detect asymptomatic AF[49].

The volume of the left atrium and the index of the left atrium to body surface area found in patients
with PAF exceeded that of patients without Paroxysmal atrial fibrillation(PAF) significantly, the
maximum left atrial volume being the most sensitive and specific parameter for detecting PAF in
patients with hypertrophic cardiomyopathy.The left atrial volume index (LAVI) provides additional
information on left atrial remodeling and predicts AF better than right atrial remodeling. It is more
important to measure LA diameter in HCM patients. When a study was conducted in 141 HCM patients,
LAVI >40 ml/m2 there is a risk of developing atrial fibrillation with great sensitivity and specifity[50].

In both the general population and HCM patients, age is a well-known predictor of AF, Age has been
found as a risk factor for the development of AF in a number of studies, with age thresholds ranging
from 40 to 50 years being independently predictive of AF in HCM patients [47].

As a result of obstructive physiology, intrinsic myocardial stiffness, mitral regurgitation, and irregular
heart rhythm, left atrial enlargement occurs in HCM, Patients with AF were more likely to have severe or
moderate mitral regurgitation ,Some studies have shown that NYHA class III/IV, moderate to severe
mitral regurgitation, and LV ejection fraction less than 50% are associated with an elevated risk of AF
[51].

In HCM, patients with a greater extent of septal hypertrophy had a greater risk of developing AF than
patients with focal hypertrophy.,those with focal septal hypertrophy and greater septum involvement
showed significantly higher LA dimensions and lower LAVIs(  the value of LA volume divided by body
surface area) compared to patients with HCM.The use of cardiac imaging has also been observed to
predict the risk of AF due to other structural factors. There is an association between septal hypertrophy
and AF risk in a study of 1360 HCM patients using ECHO and/or cardiac magnetic resonance imaging
(CMR) [52].

Paroxysmal AF can be estimated using P wave dispersion (PWD) reflecting inhomogenous atrial
conduction , By measuring LA diameter and PWD value we could easily identify patients with high risk of
developing AF with HCM, and prescribe necessary treatment and follow-up protocols for those patients,
Researchers reported 92% sensitivity and 89% specificity in the separation of patients with AF and
controls with P wave duration > 134.5 ms, In another study of 80 patients, The authors reported a
sensitivity of 96% and specificity of 91% for detecting AF as measured by P wave dispersion greater than
52.5 ms of the P wave [53].

Clinical impact of AF in HCM

AF has a noteworthy impact on the quality of life of HCM patients, and when it is combined with other
comorbidities, it can lead to heart failure, thromboembolic events, and sudden cardiac death (SCD)[54].

Patients in this group were mostly affected by symptoms of progressive heart failure. In AF, irregular
ventricular filling results from uncoordinated atrial contraction and rapid ventricular response.left
ventricular (LV) compliance is reduced in hypertrophied ventricles. This can lead to a wide range of
hemodynamic complications [55].

Due to reduced cardiac output, HCM patients with LVOT obstruction may experience hypotension,
presyncope, or syncope. In a study of 52 HCM patients, the acute onset of AF caused symptoms to
worsen in most cases, and symptoms resolved when the rhythm returned to normal [55].

HCM patients with AF have an increased risk of mortality by up to fourfold compared with individuals
with sinus rhythm, Cardiovascular deaths in AF patients are most commonly associated with
thromboembolism and worsening heart failure. There are few cases of sudden death due to
deterioration of AF into ventricular tachycardia, especially when pre-excitation is present, when a study
conducted in 480 HCM patients, about 107 patients developed AF in 9 years of follow-up [47].

In HCM, AF is common and associated with a high risk of thromboembolism. Although LA dimension and
age are independently associated with AF, the literature is not sufficient for creating robust predictive
tools. Most data suggest anticoagulation should be considered for AF patients.There is also evidence
that AF increases the risk of systemic thromboembolism (TE) in HCM patients. The incidence of TE was
3.8% per year among 7381 patients in a meta-analysis, and its prevalence was 27.1% overall [48].
AF was defined as paroxysmal when it terminated spontaneously or successfully cardioverted to sinus
rhythm, or as chronic when it became established, based on ECG recordings obtained either following
acute onset of symptoms or by chance during routine medical examination.An additional study of 480
patients found that ischemic stroke was eight times as common in the AF group as it was in the control
group (21% AF; 2.6% non-AF) [47].

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