Introduction

An enlarged heart is a medical symptom with the term "cardiomegaly."  It is not classified as an official condition or a disease but rather an underlying problem that can be associated with certain types of heart muscle damage or diseases, imposing extra stress on the heart for it to function normally.¹ This increase in demand on the heart is not necessarily caused by medical conditions such as high blood pressure or coronary artery disease; pregnancy can also contribute to extra work load, resulting in the muscle chamber of the heart either being stretched out (dilated) or thickened (hypertrophy).²

Dilation 

Heart enlargement due to muscle walls being stretched, thinned, and becoming weakened. This can result in the loss of functionality of the heart, preventing it from pumping properly.

Cardiac Hypertrophy 

The thickening of heart muscle walls to an extent that makes the heart muscle stiff, making blood circulation a harder task. This condition is usually caused by a long period of heavy workload, for example, during pregnancy. 

As heart enlargement (cardiomegaly) can be caused by a variety of conditions (including heart valve disease, cardiomyopathy, and sarcoidosis), when it comes to treatment, it is important to identify the specific cause in individual patients. Therefore, therapies can be focused on targeting the patients’ specific condition, in addition to adjusting lifestyles that benefit your heart, for example, regarding smoking and alcohol.³

Overview of the role of personalised medicine in cardiology

Personalised medicine, also known as precision medicine, is a form of medicine practice that uses an individual's unique genetic profile in order to design the most beneficial treatments for the patients’ diagnosis. The advancements in genomic analysis and molecular diagnostics have allowed clinical practice to move forward from the “one size fits all” approach to treat patients with the same condition. By understanding the role our own DNA plays at the molecular level, it is even possible to predict the outcome and prevention of the disease.⁴

Despite that, personalised medicine does not play as much of a role in cardiology in comparison to oncology. Personalised medicine is still considered a sensible strategy with great potential in revolutionising cardiovascular therapies in the future, regarding:

• Its capability to contribute to more manageable grouping 
• Differentiation of population to shift the focus from the traditional overall therapies to targeted specific therapies
• Maximising clinical outcomes for cardiovascular disorders⁵

Personalised Medicine in Heart Enlargement Testing

One major route towards personalised medicine is genetic testing. Due to the advancements in genetic sequencing technology, such as next-generation sequencing (NGS) in the past decades, genetic testing and therapy are becoming more common in modern clinical settings. This has made personalised medicine a focus in clinical research for cardiovascular diseases (CVDs), including conditions causing an enlarged heart.⁶

Genetic Diagnostic Test

The diagnostic power of genetic testing has been proven to be indispensable across the spectrum of CVDs. Examples of successful use of genome sequencing and interpretation for disease outcome and diagnosis can be found in clinical settings back in 2010. 

This approach was performed on a patient with a family history of sudden death associated with coronary artery disease (CAD), which can be potentially a cause of cardiomegaly. The cardiac clinical team conducted genomic analysis of his genomic profile to assess an increased risk for myocardial infarction as well as type II diabetes. A pharmacogenomic test was also performed on the patient to assess his potential response to certain drugs and show any potential drug resistance the patient might have due to genetic mutations.⁶ This result had showcased the capability of personalised medicine for the evaluation of risk by providing relevant clinical information about the patients. 

Pharmacogenetic testing

The greatest advantage of personalised medicine is that pharmacogenetic tests allow the prescription of the most effective drugs,  avoiding drugs with potential side effects and drug resistance. These approaches reduce both time and cost, maximising treatment outcomes. In pharmacogenetics, genomic information is used to evaluate an individual's response to certain drugs in clinical settings; in the research field, it can also be used to identify new therapeutic targets for innovation of new generations of drugs.

The significance of individualised therapeutic interventions, including pharmaceutical treatments, needs to be demonstrated in a disorder as widespread as hypertension. This is because hypertension is an essential factor that needs to be controlled for prevention of CVDs and stroke mortality, as well as cardiomegaly.⁵ In a traditional clinical setting, the slight variations in phenotypes of each individual hyertensive patient are rarely considered when it comes to selection of antihypertensive medications. Medicine can provide opportunity for better clinical outcomes for a global public health issue.

Personalised Pacemakers

Personalised medicine isn’t only about prescribing the right drugs; it has the potential to offer the best medical device assigned to suit each individual patient, such as a personalised pacemaker. A pacemaker is a medical device that can be surgically implanted into a patient's heart to regulate heart rate by sending electrical impulses. According to researchers Dr Sam Straw and Dr Klaus Witte at the University of Leeds, the current “one size fits all” algorithm does not always provide sufficient improvement in exercise in patients.⁷ It is suggested that this is because the algorithm is based on the heart rate of a healthy individual. They are now investigating  how to improve more patients’ lives with heart failure by personalised pacemaker programming, which personalises the heart rate to each patient. 

Challenges and Limitations

Although personalised medicine is already being practised in clinical settings and the use of genomic tools is becoming more and more common, the limitations of relying on personalised medicine are clear. Aswith cancer, the development of CVDs is multifactorial and depends on various factors other than genetic factors, such as environmental factors, and the existence of epidemiological issues, which tend to be independent of genomic factors.⁸

For example, the benefits from performing pharmacogenetic tests are not to be neglected, but in reality, genetics only account for a relatively small percentage of response variability to a prescribed drug. This is because the complexity of drug response includes, and also requires, more information beyond genomic profiles.

Future Directions

In personalised medicine, the genome can be analysed, as well as targeted, for more precise therapeutic treatments for CVDs. Although there is still a long way to go before personalised medicine, in particular genome editing, it becomes a common and viable option as CVD treatment. For example,  innovations in gene editing technologies such as CRISPER have already taken this investigation forward.⁶ 

CRISPER is a system that acts as biological scissors, cutting and editing the target DNA sequence in order to correct genetic mutations that cause cardiovascular disorders, hence reversing the disease phenotype on a genome level. Of course we must not forget that genes never act alone; lifestyle, diet, and exercise can all contribute towards the modification of cardiovascular diseases and the prevention of cardiomegaly.

Another issue arising from advancement in gene editing therapy is the ethical and safety concerns. The risk of the CRISPR system mistargeting and accidentally cutting, deleting, or replacing non-faulty genes can lead to serious consequences. 

Conclusion

The ultimate goal of personalised medicine is to predict, prevent, treat, and cure diseases with reduced trial-and-error approaches. It is the future of medicine and already holds promising results for cardiovascular disorders therapeutics Despite the fact that many technologies are still in the early stage, challenges are clear. 

In addition, although multiple genetic studies have been conducted, the target populations of those studies are mostly from European countries, which indicates the lack of data across diverse ethnic populations. It is important to expand data collection for personalised medicine research, as variants associated with disease phenotypes and pharmacogenomic responses may differ hugely across different populations.⁶ 

Furthermore, the research on personalised medicine is affected by multiple aspects other than clinical application and evidence-based practices, including:

• Socioeconomic
• Ethical, regulatory
• Educational

Education refers to both doctors and patients, as most cardiologists do not feel confident in their understanding of personalised medicine. Approximately 6% of patients had asked about personalised medicine to their doctors.⁸ It is essential to raise public awareness and knowledge related to personalised medicine in order for the era of personalised medicine to thrive.

FAQs

What can lead to an enlarged heart (cardiomegaly)? 

• Heart Diseases including: 
• Coronary heart disease
• Heart valve disease
• Cardiomyopathy
• High blood pressure
• Pregnancy
• Infections in heart, such as myocarditis
• Drugs and toxins (recreational drugs;alcohol;certain chemotherapy drugs)

In addition, rapid aerobic exercises may also lead to heart enlargement, but this is usually not a case for concern.²

What are the treatment options for cardiomegaly?

Treatments depend on the causation of an enlarged heart, and medications can be prescribed targeting the causations. If medications are unable to control or suppress the condition, surgery may be recommended, as well as implantation of medical devices.⁹

Medications:

• Blood pressure medications including:
• Diuretics; ACE inhibitors (angiotensin-converting enzyme); ARBs (angiotensin II receptor blockers)
• Blood thinner medications
• Heart rhythm medications

Surgery:

• Implantation of pacemaker
• Implantation of implantable cardioverter-defibrillator (ICD)
• Heart valve surgery
• Coronary bypass surgery