NEW YORK — Late-onset dilated cardiomyopathy might represent a distinct disease subtype marked by an increased burden of genetic variants, a new study has found. The findings further suggested that genetic testing may be beneficial for older dilated cardiomyopathy patients.
Dilated cardiomyopathy is marked by decreased function of the left ventricle and is most commonly diagnosed among people in their 30s or 40s, though an increasing number of cases have been identified in people over the age of 60 years.
An international team of researchers sought to examine the genetic variation found among individuals with late-onset dilated cardiomyopathy. As they reported in JAMA Cardiology, they found that more than a third of patients in their cohort had a known pathogenic or likely pathogenic variant, most commonly a Tintin-truncating variant (TTNtv), and that patients with these pathogenic or likely pathogenic variants had a higher mortality rate than those who did not.
These findings "support the extended use of genetic testing also in older patients," senior author Gianfranco Sinagra, a professor at the University of Trieste in Italy, and his colleagues noted in their paper.
The researchers enrolled 184 patients from seven different health centers around the world who were diagnosed with dilated cardiomyopathy at a mean age of 67 years old. The consecutively ascertained cohort included 103 women and 81 men, a sex ratio that differs from the 3-to-1 male-to-female ratio observed among younger-onset dilated cardiomyopathy.
The patients in the cohort underwent genetic testing on next-generation sequencing multigene panels for dilated cardiomyopathy. Through this, the researchers reached genetic diagnoses for 36 percent of patients, a yield similar to that observed among younger patients.
The most common variants in this cohort were TTNtvs, which affected 46 patients, or 69 percent of those with a genetic diagnosis. TTNtvs appeared nearly twice as common among this late-onset dilated cardiomyopathy cohort than has been reported among younger-onset dilated cardiomyopathy cohorts. Twenty other patients had other pathogenic or likely pathogenic variants in LMNA, FLNC, and other genes.
After following the cohort for a mean 42 months, the researchers found that patients with a genetic diagnosis were more likely to die than patients with a negative genetic test.
These findings suggested to the researchers that late-onset dilated cardiomyopathy might represent its own disease, as it is marked by an increased prevalence among women, a higher proportion of TTNtvs, and worse prognosis among gene-variant carriers. This prevalence of TTNtvs further indicated to them that there may be a gene-environment interaction at play, as TTN has been suspected of being a modifier of environmental factors, rather than a Mendelian gene, and suggested that aging and comorbidities associated with aging might act as a second insult to contribute to the development of late-onset dilated cardiomyopathy.
Because of this and the associated worse prognosis they uncovered, the researchers said that "genetic testing might be considered in patients with [dilated cardiomyopathy] diagnosed when they are older than 60 years."