Study Identifies Genetic Mutations Linked to Peripartum Cardiomyopathy

Researchers from the University of Pennsylvania School of Medicine have identified additional genetic mutations that strongly predispose otherwise healthy women to peripartum cardiomyopathy (PPCM), a rare condition characterized by weakness of the heart muscle that begins sometime during the final month of pregnancy through 5 months after delivery. PPCM often leads to lifelong heart failure and can result in severe heart failure and death.

The cause of PPCM was entirely unknown until a 2016 study suggested that certain genetic mutations predispose women to the disease. The current study identifies 4 additional genetic variants that were not previously connected to PPCM.

According to the researchers, this genetic profile is highly similar to that found in patients with non-ischemic dilated cardiomyopathy (DCM), a very similar disease that is better understood and that typically impacts middle-aged men and women.

“This study provides the first extensive genetic and phenotype landscape of PPCM and has major implications for understanding how PPCM and DCM are related to each other,” said Zoltan P. Arany, MD, PhD, in a press release. “It shows that predisposition to heart failure is an important risk factor for PPCM, suggesting that approaches being developed for DCM may also apply to patients with PPCM.”

PPCM affects women at a rate of 1 in 2000 deliveries globally, with approximately one-third of those affected developing heart failure for life and 5% dying within a few years of developing the condition. Maternal mortality has doubled over the past 20 years, with PPCM as a leading cause of death, according to the study authors.

In order to conduct the study, researchers identified approximately 470 women with PPCM and examined their clinical information and DNA samples. They performed sequencing on 67 genes, including a gene known as TTN, which generates a large protein that controls how heart muscle cells contract and pump blood.

The researchers found that 10.4% of the patients sampled showed shortened variants in the TTN gene compared to 1.2% of the reference population. They also found overrepresentation of shortened variants in 3 other genes not previously associated with PPCM that had been previously associated with DCM.

“We believe this study shows how important genetic screening and counseling are for women who develop PPCM, something that isn't currently common practice, and perhaps even for their female family members of child-bearing age,” Arany said in the release. “As a physician, knowing you have a patient with PPCM who shows these genetic mutations would lead you to make changes in care, such as lowering the threshold for defibrillator use in the case of high-risk variants, or counseling family members on their risk of developing PPCM.”

The researchers hope this will allow physicians to follow similar genetic testing practices and counseling guidelines as those implemented for patients with DCM, as well as gene-specific therapies. Though the study has identified which genes play a role in the development of PPCM, further study is required to understand how pregnancy triggers this condition in some women with a specific genetic predisposition, as not all women with these gene variants develop PPCM when they get pregnant.


Study helps unravel why pregnant women develop heart failure similar to older patients [news release]. EurekAlert; April 20, 2021. Accessed April 22, 2021.