Discussion
Initially, we hypothesized that the myocardial hypertrophy observed in
this case was primarily attributed to secondary hypertension caused by
primary aldosteronism (PA). However, the left ventricular wall
thickness, ranging from 15 to 22mm, exceeded what is typically seen in
hypertensive hypertrophy (usually around 13-14mm). Conversely, an
average left ventricular wall thickness of 21mm is commonly observed in
cases of Hypertrophic Cardiomyopathy (HCM) [2]. Additionally, HCM
alone cannot fully explain the presence of left atrial hypertrophy.
Therefore, we propose that the changes observed in this particular case
are likely a complication resulting from both HCM and PA.
To further validate our assumption, we conducted a comprehensive
analysis of the patient’s whole exome sequencing data. We focused on
identifying pathogenic variations by cross-referencing with the OMIM
database. Our assessment revealed suspected variants in TTN, SLC36A2,
and TWNK genes.
Familial hypertrophic cardiomyopathy (HCM) is known to be associated
with various gene mutations, including MYH7, MYBPC3, TNNT2, GLA, and
TTR. However, the presence of TTN, SLC36A2, and TWNK mutations in this
particular case appears to be rare and has not been widely reported
[2][3]. TTN encodes a large protein found abundantly in striated
muscle and myocardial cells. Mutations in this gene have been linked to
familial hypertrophic cardiomyopathy 9. Additionally, patients with the
autoimmune disease scleroderma often produce autoantibodies targeting
titin.
SLC36A2 is primarily expressed in renal cells but has no documented
reports linking it to the pathogenesis of HCM. TWNK mutations are
responsible for infantile onset spinocerebellar ataxia (IOSCA),
progressive external ophthalmoplegia (PEO), as well as several
mitochondrial depletion syndromes. Considering the patient’s clinical
history and examination findings mentioned earlier, we identified a
suspected pathogenic variation within the TTN gene as being potentially
relevant to this case study.
These findings provide additional support for our hypothesis regarding
the involvement of multiple genetic factors in this case, contributing
to both hypertrophic cardiomyopathy (HCM) and primary aldosteronism
(PA). The identification of these specific gene variants adds valuable
insights into understanding the underlying mechanisms and potential
genetic basis for this rare clinical presentation.
In addition to our investigation into the genetic factors associated
with HCM in this case, we also sought to explore whether there might be
a shared genetic mutation underlying both HCM and primary aldosteronism
(PA). Our review of relevant literature and summaries on PA yielded some
interesting findings: The exact pathogenesis of PA is not yet fully
understood. However, it is believed that somatic mutations occurring in
ion channels and pumps within adrenal cells play a role in initiating
the development of PA [4]. Studies focusing on three types of
Familial Hyperaldosteronism have identified mutations in genes such as
CYP11B1, CYP11B2, CLCN2, GIRK4, and CACNA1D [5][6][7]. These
gene mutations may provide insights into potential pathways involved in
the pathogenesis of PA.
By considering these facts and examining possible connections between
HCM and PA at a genetic level, we aim to shed light on any potential
shared mechanisms or common underlying genetic variations that could
contribute to both conditions.
(HCM) and primary aldosteronism (PA) has been associated with a poor
prognosis [1]. Compared to primary hypertension, PA has been shown
to cause more damage to end-organs and is linked to increased
cardiovascular morbidity. This includes conditions such as heart
failure, non-fatal myocardial infarction, and atrial fibrillation
[8][9]. Additionally, HCM itself can lead to progressive heart
failure symptoms due to obstructive physiology and diastolic
dysfunction. Therefore, maintaining positive control over blood pressure
levels in patients with HCM becomes crucial. By achieving a target blood
pressure of 120/80mmHg in these patients, it may help decrease both
preload and afterload on the left ventricle. This approach holds
potential for positively impacting the prognosis of this particular
complication.
By recognizing these factors and implementing appropriate management
strategies for both HCM and PA, we aim to improve patient outcomes and
mitigate the risk of adverse cardiovascular events associated with this
challenging combination.
Based on the guidelines for hypertrophic cardiomyopathy (HCM) and
primary aldosteronism (PA), we have devised a treatment plan as follows:
Sacubitril/valsartan 100mg twice daily: This medication combination has
been shown to be effective in managing heart failure symptoms and
improving outcomes in patients with HCM [4]. Nifedipine 30mg once
daily: Nifedipine is a calcium channel blocker that helps relax blood
vessels, reducing blood pressure and alleviating symptoms associated
with PA [10]. Bisoprolol 5mg once daily: Bisoprolol is a
beta-blocker that can help control heart rate and reduce cardiac
workload, which may be beneficial for patients with both HCM and PA
[4].
Additionally, it is worth noting that mavacamten, an investigational
therapy for HCM, has shown promising results in reducing obstruction of
blood flow, improving symptoms, overall well-being, and enhancing the
ability to engage in daily activities [10]. However, there is
currently no evidence regarding its use specifically in PA patients.
At the time of completing this report, our management approach has
successfully controlled blood pressure within the range of
120-130/70-80mmHg. Further follow-up will be necessary to monitor any
changes in myocardial health. By combining appropriate pharmacological
interventions tailored to address both HCM and PA conditions, we aim to
optimize patient care while considering their individual needs and
potential benefits from emerging therapies such as mavacamten.