Precision: the new Tinder Belle of the Heart

Precision medicine is an emerging approach to medical care.  It takes into account individual variations in genetic make-up, metabolism and other biological and environmental factors, to better determine which treatment and prevention strategies for a particular disease may work better for which groups of people1.

Today, precision medicine is routinely integrated into the care of cancer patients, and has provided substantial increases in cancer free survival2. For example, translational studies investigating signatures within the tumour that promote disease progression, can predict individual responses to standard and targeted chemotherapy regimens2,3.

In the cardiovascular field, even though the prognosis for people with heart failure has improved in recent decades as research studies demonstrate the effectiveness of various medications, precision medicine is still in its infancy.

Some aspects of precision medicine are routinely used by healthcare providers, like the blood level of the biomarker called B-type natriuretic peptide, which is a sensitive indicator of whether heart failure is worsening or if treatments are helping1,4. This biomarker can also help the doctor determine whether shortness of breath symptoms in an individual are due to heart failure, or another medical problem1.

But as it is now, patients diagnosed with heart failure are still offered essentially identical treatments, regardless of whether their disease was caused by coronary artery disease, genetic mutations, or an autoinflammatory processes2

Also, historically, clinical trial participants have been predominantly white people with particular genetic variants; but, individuals with different racial and ethnic ancestry have different genetic variants, and therefore, may not have the same response to a certain medication or treatment1.

While this “one-size-fits-all’ approach has led to improvements in clinical outcomes in large populations, the individual response rates continue to vary tremendously; and, it is often difficult to distinguish patients who will achieve a favourable response, from those who will experience disease progression, and ultimately succumb to their illness2.  

As such, in the cardiovascular field, it is urgent to personalize heart failure care by identifying groups of patients more likely to develop heart failure, and tailoring which medications and other therapies could be most effective for them1. Currently, many individuals are left poorly treated, and there is substantial room for improvement2.

Key studies demonstrating selective efficacy of certain drugs in patients harbouring specific genetic variants, indicate a direction where treatment responses can be predicted using individual genetic information. 

Given the recent cost reductions in exome sequencing, for example, this can now be used routinely to identify genetic variants that predict heart failure prognosis, and specific responses to medical and device-based therapies. Such information can further provide critical insights into new disease mechanisms, like Lamin A mutations that display a molecular phenotype that is dramatically distinct from other forms of dilated cardiomyopathy5

More and more we come to realize that despite a common surface phenotype or symptomology, certain mutations may actually give rise to distinct diseases that need to be appropriately treated.

As such, researchers need to increase clinical trial diversity, so that optimal treatment approaches can be found for each population group. Also, the power of supercomputing should be used to rapidly predict the outcomes of possible new treatments. And, processes for sharing information across large databases shouldbe put in place with guarantees of patient privacy (e.g., cloud-based platforms), so that clinicians/scientists can quickly collaborate and share data internationally.

Moreover, updated health-wearable devices, artificial intelligence and other deep learning technologies strategies will ultimately be employed to develop testable hypotheses from large datasets, and provide precision-personalized approaches to cardiovascular health care.

Let’s hope Precision will be more than a one night stand on Heart’s Tinder list….

Yayoi Kusama art installation, Berlin Modern Art Museum

References:

1          AHA. Emerging practice of precision medicine could one day improve care for many heart failure patients. Heart.org https://newsroom.heart.org/news/emerging-practice-of-precision-medicine-could-one-day-improve-care-for-many-heart-failure-patients?utm_campaign=sciencenews19-20&utm_source=science-news&utm_medium=phd-link&utm_content=phd09-12-19 (2019).

2          Kory J. Lavine, C. E. C. Precision Medicine for Heart Failure: using “omics” technologies to find the road to personalized care. Heart.org https://professional.heart.org/en/science-news/heart-failure-in-the-era-of-precision-medicine/Commentary (2021).

3          Prasad, V., Fojo, T. & Brada, M. Precision oncology: origins, optimism, and potential. Lancet Oncol. https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(15)00620-8 17, e81-e86, doi:10.1016/s1470-2045(15)00620-8 (2016).

4          Maisel, A. B-Type Natriuretic Peptide Levels: Diagnostic and Prognostic in Congestive Heart Failure. Circulation. https://www.ahajournals.org/doi/10.1161/01.CIR.0000019121.91548.C2 105, 2328-2331, doi:doi:10.1161/01.CIR.0000019121.91548.C2 (2002).

5          Cheedipudi, S. M. et al. Genomic Reorganization of Lamin-Associated Domains in Cardiac Myocytes Is Associated With Differential Gene Expression and DNA Methylation in Human Dilated Cardiomyopathy. Circ Res. https://pubmed.ncbi.nlm.nih.gov/30739589/ 124, 1198-1213, doi:10.1161/circresaha.118.314177 (2019).

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