A team of researchers led by the Miller School's Ray E. Hershberger, M.D., professor of medicine and associate director of the Cardiovascular Division, has for the first time established that some cases of cardiomyopathy during or shortly after pregnancy have a genetic cause.

Their study, Rare Variant Mutations in Pregnancy-Associated or Peripartum Cardiomyopathy, will be published in the May 25 edition of Circulation but appeared Monday in the online version of the nation's leading journal of cardiovascular medicine. The article provides clinicians critical information on managing women, as well as the families of the women, who are diagnosed with cardiomyopathy, or heart muscle disease, of unknown cause during or after pregnancy.

"There are literally thousands of women who have had peripartum cardiomyopathy but have no idea what caused it,'' Hershberger said. "Some have died, some have had heart transplants and some live with severe heart dysfunction. What we have shown is that in some cases it has a genetic cause. They need to know that because it has dramatic implications for screening their offspring, as well as their siblings and parents. With an early indication of dilated cardiomyopathy in their at-risk family members, we can start treatment to prevent advanced or end-stage disease.''

The most common form of cardiomyopathy, dilated cardiomyopathy (DCM) is characterized by a weakened heart muscle that doesn't pump efficiently; most patients who have it eventually develop heart failure.

Hershberger began the Familial Dilated Cardiomyopathy Project at Oregon Health & Science University in 1992, hoping to discover the genetic causes of DCM and translate that information into better cardiovascular care. At the time, there were no known genes associated with DCM.

Now, with mutations identified in more than 30 genes, there is considerable research establishing a genetic basis for a proportion of DCM of an unknown cause. But Hershberger and his team are the first to formally test the hypothesis that rare DCM-associated mutations underlie a proportion of cases of peripartum cardiomyopathy and pregnancy-associated cardiomyopathy. Peripartum cardiomyopathy has been defined as DCM occurring in the last month of pregnancy to five months postpartum. Pregnancy-associated cardiomyopathy is used to describe DCM occurring earlier in pregnancy.

Searching their database of 4,110 women from 520 families with one or more cases of DCM of unknown cause, the team identified 45 women who were diagnosed with the disease during or shortly after pregnancy. Of those 45 women, 19 underwent genetic testing for a subset of genes, which when altered or mutated can cause DCM. Of the 19 women, six carried DCM-associated mutations, a finding that, the paper says, shows that a proportion of DCM cases of unknown cause that occur during or shortly after pregnancy "results from a genetic cause.''

Several of these women were in families with other documented cases of DCM, or familial dilated cardiomyopathy; others were apparently sporadic cases of peripartum or pregnancy-associated cardiomyopathy.

Because the findings demonstrate that cardiomyopathies of unknown cause that develop during or after pregnancy may have genetic causes just like DCM diagnosed outside of pregnancy, the paper recommends that clinicians caring for patients with peripartum or pregnancy-associated DCM consider the same guidelines for family cardiac screening and genetic testing as those recommended for new diagnoses of DCM of unknown cause.

Published last year, the new guidelines for DCM of unknown cause, which Hershberger co-authored with other leading genetic cardiomyopathy experts, urge clinicians to consider the possibility of a genetic cause in familial and apparently sporadic cases.

Per those new guidelines, the Circulation study recommends that a genetic evaluation, including family history, clinical screening with an echocardiogram and ECG, and genetic counseling and testing should be conducted for patients diagnosed with DCM of unknown cause during or shortly after pregnancy, and for their first-degree relatives. Although peripartum cardiomyopathy and pregnancy-associated cardiomyopathy are rare, the paper continues, these conditions may occur more frequently among relatives of patients with DCM of unknown cause, and therefore reproductive risk counseling about peripartum and pregnancy-associated cardioymyopathy is appropriate for the first-degree female relatives of such patients in the context of genetic cardiomyopathy evaluation.

In addition to Hershberger, the study authors include genetic counselor Ana Morales, M.S., C.G.C, formerly of the Miller School; third-year medical student Thomas Painter, B.S.; summer intern Ran Li, B.S.; genetic counselor Jill D. Siegfried, M.S., C.G.C.; Duanxiang Li, M.D., M.S., assistant professor of medicine; and Nadine Norton, Ph.D., research assistant professor of medicine.

Hershberger hopes their latest finding will open the door to more genetic studies of peripartum cardiomyopathy. "We need more sophisticated, more targeted and much more comprehensive studies of the genetics of peripartum cardiomyopathy,'' he said.

He also suggests that women with known peripartum cardiomyopathy contact his UM research group to participate in their ongoing studies. For more information, visit the website of the Familial Dilated Cardiomyopathy Project, which moved to the Miller School in 2007, at http://www.fdc.to/.