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.