CHICAGO – Henry Ford Health and Illumina have enrolled the first 1,000 patients into CardioSeq, a clinical trial assessing the clinical utility of whole-genome sequencing in cardiovascular care.
So far, more than 200 patients have had a genomic finding from this testing, including 100 individuals who learned they are at increased risk for cardiovascular disease, researchers reported during a poster session at the American College of Cardiology's annual scientific meeting this weekend.
Investigators launched the prospective, open-label CardioSeq trial in 2023. The organizations intend to enroll 1,500 patients in total at Detroit-based Henry Ford Health. In order to participate and receive genomic testing in the trial, patients must be diagnosed with cardiomyopathy, heart failure, aortopathy, arrhythmia, coronary or peripheral artery disease, or dyslipidemia.
Generally, genetic testing has been underutilized in cardiovascular care, despite clinical practice guidelines recommending it for some inherited conditions. The clinical trial grew out of a desire to better understand the prevalence of genetic diseases within cardiology clinics, said Damon Hostin, health system market access lead at Illumina, which is funding the study.
In CardioSeq, "the inclusion [criteria] is broad, with the exception that a patient has to have been referred to a cardiology sub-clinic," he said. All patients who enroll in the study are adults with stable disease and who have engaged routinely with the cardiology clinic at Henry Ford Health.
Patients are assessed using a comprehensive clinical genome sequencing (cGS) test developed by Illumina that screens for more than 200 genetic causes of cardiovascular disease, for abnormalities in 35 other genes from the American College of Medical Genetics and Genomics' secondary findings list that are unrelated to cardiovascular disease, and for pathogenic variants in 10 pharmacogenes associated with drug response and adverse events. The test also assesses four alleles known to increase heart disease risk and determines a coronary artery disease polygenic risk score.
Researchers share the results with patients and their cardiologists, and patients with clinically relevant findings from genomic testing go on to receive genetic counseling. Investigators from Henry Ford Health and Illumina may also use the genetic and clinical data gathered in the study for translational research into genomic medicines, Hostin said.
Of the first 1,000 patients enrolled, 22 percent have received at least one finding from genomic testing. Seventy-four participants have received a monogenic finding, about half of whom have a pathogenic variant in one of three genes linked to cardiovascular disease: 16 patients in TTR, 14 patients in TTN, and eight patients in LDLR.
One-fifth of patients with a monogenic finding specifically were found to be carriers of the V142I variant, a mutation in the TTR gene associated with hereditary transthyretin (TTR) amyloidosis cardiomyopathy. V142I is the most common variant associated with this rare and inherited heart condition in the US and which is primarily seen in Black patients.
These findings can help guide patients' care, including prompting cascade testing for family members or closer monitoring for patients, Hostin said. Additionally, there are a growing number of medications on the market and in clinical trials that target such genetic abnormalities. For example, certain drugs for TTR amyloidosis may require that patients have a TTR mutation.
Additionally, the researchers found that 100 patients, or 10 percent of the study cohort, are carriers of an allele that puts them at increased risk for cardiovascular disease.
Hostin noted the diverse sample with 58 percent of participants whose self-reported race was White and 39 percent whose self-reported race was Black. The cohort included nearly equal numbers of patients who were assigned male or female at birth.
These are just the initial findings from the CardioSeq study, noted Whitney Cabral, a research operations manager at Henry Ford Health and project manager for the study. Investigators will continue to study how the clinical care of patients with genomic findings compares to those receiving standard care, including whether cardiologists adjust patients' care plans and if that affects their clinical outcomes.
Researchers will report these results at the end of the CardioSeq study. "This is just the tip of the iceberg for us," Cabral said.