March 21, 2023 | The worlds of genetics, epigenetics, and artificial intelligence (AI) have united to enable development of a blood test for the early detection of coronary heart disease (CHD). Newly launched in the U.S. by Cardio Diagnostics (Nasdaq: CDIO), PrecisionCHD is underpinned by the same technology as the company’s predecessor Epi+Gen CHD risk assessment test but using a different set of genetic and DNA methylation biomarkers, according to Chief Executive Officer Meesha Dogan, Ph.D.
This also makes PrecisionCHD the second clinical test built using Cardio Diagnostics’ AI-driven Integrated Epigenetic-Genetic Engine, the only real-world option where epigenetics is being applied to the diagnosis of heart disease, she says. The rollout is accompanied by the provider-only Actionable Clinical Intelligence (ACI) platform that maps the unique biomarker profile of patients to modifiable CHD risk factors such as diabetes, hypertension, hypercholesterolemia, and smoking.
And this is just the beginning for Cardio Diagnostics, says Dogan. Moving forward, the company will “develop patient assessment and management tools” for other major cardiovascular diseases, including stroke and heart failure.
The goal is not to eliminate exercise electrocardiograms or angiograms but for doctors to use PrecisionCHD—available via prescription only—as part of a more comprehensive assessment of modifiable drivers for coronary heart disease. Patients can and sometimes do have a heart attack during the wait for their initial stress test, Dogan notes.
Physicians can instead order PrecisionCHD and give patients the option of having the test done remotely via a blood collection kit and telemedicine, she adds. Since this is a laboratory developed test (LDT), results come out of a facility meeting all applicable requirements of the Clinical Laboratory Improvement Amendments (CLIA) program for high complexity testing. A single, centralized CLIA lab based in St. Louis, Missouri, presently does all the biomarker testing.
The technology will first be available exclusively for existing customers, says Dogan, with a nationwide rollout expected around the end of this month. The current user base is comprised of physicians specializing in concierge medicine and executive health who have been using the Epi+Gen CHD test and were awaiting release of PrecisionCHD.
As has been publicly reported, Cardio Diagnostics is pursuing a regulatory pathway with the U.S. Food and Drug Administration, Dogan says, although this is “not a guaranteed way of getting a test covered [by payers].” Launching PrecisionCHD as an LDT allows the test to more immediately provide its benefits to “hundreds of thousands if not millions of Americans” as evidence-sharing continues with the payer community.
In support of the Epi+Gen CHD risk assessment test, Cardio Diagnostics points to a 2021 study done in collaboration with Intermountain Healthcare (Epigenomics (DOI: 10.2217/epi-2021-0123)) showing the improved sensitivity compared to current lipid-based methods for predicting CHD risk. A similar type of study, again with Intermountain Healthcare, is now working its way to peer-reviewed press for the PrecisionCHD test, Dogan says.
At a presentation recently made on both tests at the American College of Cardiology conference, the PrecisionCHD test was described as “a sensitive and non-invasive alternative to exercise stress tests, nuclear stress tests, stress echocardiograms, coronary angiograms, and cardiac catheterization... to detect the presence of coronary heart disease.”
When Dogan began studying epigenetics at the University of Iowa, most everyone else was focused on genetics. At the time, her group was one of the only ones on campus doing epigenetics. “We didn’t even have a tool or technology to measure DNA methylation at a genome-wide scale,” she recalls, although her group was one of the first to adopt Illumina’s first-to-market genome-wide array around 2010.
That took care of the measurement issue but created a scalability problem. So, at roughly the same time, Dogan and her colleagues began incorporating machine learning and AI into their work.
The more fundamental scientific limitation was that “only about 20% of our risk for heart disease comes from our genetics,” she says. “That means the 80% left is largely what we can modify and control... to better change our risk profile.”
Dogan’s doctorate work in biomedical engineering—specifically for heart disease—was about closing the knowledge gap by joining genetics, epigenetics, and AI, and it resulted in the Integrated Genetic-Epigenetic Engine coinvented with her thesis advisor Robert Philibert, M.D., Ph.D. Based on the patented technology, they cofounded Cardio Diagnostics in 2017.
Cardio Diagnostics is looking to eventually address the entire “continuum of coronary heart disease,” says Dogan, including individuals with and without CHD signs and symptoms such as angina as well as those who have had a CHD event. With Epi+Gen CHD and PrecisionCHD, the idea is to “prevent people from crossing the threshold” and having a heart attack.
Epi+Gen CHD launched in 2021, at the height of the COVID pandemic, as a test that could be performed remotely in partnership with telemedicine provider InTeleLabs providing consumer access to the test via its elicity platform. But a year later, Cardio Diagnostics found an audience with large concierge medical groups who began offering the precision cardiovascular disease test to their patient pool, Dogan says.
Many people, including healthcare providers, are eager to learn about epigenetics, continues Dogan. Educational efforts focused initially on healthcare providers “because they are the ones seeing patients day to day,” but have since expanded to include large integrated delivery networks, health systems, employers, and payers.
Prevention of heart attacks and other cardiac events has great value from a dollars-and-cents perspective as well as in saving and improving the quality of lives. In a 2021 cost–utility analysis (Epigenetics, DOI: 10.2217/epi-2021-0021), the Epi+Gen CHD test was associated with better survival and attractive negative incremental cost–effectiveness ratios ranging from -$42,000 to -$8,000 per quality-adjusted life year.
Health equity has been the focus of talks with payers about covering Cardio Diagnostics’ tests, Dogan says. The complication on this front is that “no two payers have asked exactly the same questions or told us exactly the same things they need to be able to cover the test.”
Most recently, the company shared that PrecisionCHD has the potential to drive new insights even for pharmaceutical companies where heart disease is a concern as a companion diagnostic. The test is also ideally suited for decentralized clinical examinations of lifestyle interventions for at-risk individuals.
The newly-introduced ACI platform giving doctors biomarker-based information on modifiable CHD risk factors has seemingly vast potential in motivating behavioral changes in patients. In one study, significant improvement in DNA methylation markers of the Epi+Gen CHD test was observed in as little as 90 days among subjects enrolled in a smoking cessation program, Dogan reports.