Novel blood analysis suggests inflammation ‘plays a role’ in peripartum cardiomyopathy
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Key takeaways:
- Peripartum cardiomyopathy is a distinct disease entity relative to nonischemic cardiomyopathy.
- The condition is characterized by unique dysregulation of inflammation- and cholesterol-related pathways.
New serum proteomic analyses suggest that a distinct dysregulation of inflammatory and cholesterol-related pathways drive peripartum cardiomyopathy, a rare but serious complication of pregnancy occurring more frequently among Black women.
Because some patients with peripartum cardiomyopathy exhibit mutations also associated with other forms of dilated cardiomyopathy, researchers have debated whether peripartum cardiomyopathy is a distinct disease or the manifestation of an underlying cardiomyopathy precipitated by the hemodynamic stresses and hormonal imbalances of the peripartum period, Luigi Adamo, MD, PhD, assistant professor of medicine at Johns Hopkins University School of Medicine, and colleagues wrote in JACC: Heart Failure.
“Peripartum cardiomyopathy is one of the great unmet needs of modern cardiology,” Adamo told Healio. “It affects young women during a very vulnerable moment in their lives. When these women get sick, there is also a great impact on their families, and there are limited therapeutic options.”
Serum ‘omics’ analysis
Researchers have identified several risk factors for peripartum cardiomyopathy, including preeclampsia, genetic predisposition and vasculo-hormonal factors, Adamo said. Evidence suggests inflammation may contribute to peripartum cardiomyopathy; however, researchers have not yet identified specific immunological pathways dysregulated in women with the condition.
“One of the big questions in peripartum cardiomyopathy is etiology,” Adamo said during an interview. “There are plenty of ways of looking at the physiopathology of a disease at a high level. One of the most powerful is using an ‘omics’ approach. The idea was to look at the serum of patients with cardiomyopathy along with the right controls.”
Adamo, Jana P. Lovell, MD, a cardiology fellow at Johns Hopkins Medicine, Healio | Cardiology Today Editorial Board Member Garima Sharma, MD, FAHA, director of women’s cardiovascular health and cardio-obstetrics at Inova Health System in Falls Church, Virginia, and adjunct associate professor of medicine at Johns Hopkins Medicine, and colleagues conducted an aptamer-based proteomic analysis on serum samples from 67 women with peripartum cardiomyopathy, 31 women with recent-onset, nonischemic nonperipartum cardiomyopathy, as well as age-matched healthy peripartum (n = 10) and nonperipartum women (n = 10), using data from the Investigations of Pregnancy-Associated Cardiomyopathy (IPAC) and Intervention in Myocarditis and Acute Cardiomyopathy (IMAC2) studies.
“The pathophysiology of peripartum cardiomyopathy remains incompletely understood,” Lovell told Healio. “To address this gap in knowledge, we performed high-throughput aptamer-based serum proteomic analysis of women with peripartum cardiomyopathy compared to women with nonperipartum nonischemic cardiomyopathy.”
In principal component analysis, researchers observed a unique clustering of each patient group (P for difference < .001).
In biological pathway analyses of differentially measured proteins in peripartum cardiomyopathy relative to nonperipartum cardiomyopathy, before and after normalization to pertinent healthy controls, researchers observed specific dysregulation of inflammatory pathways in peripartum cardiomyopathy, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (P < .01; z score, 1.9-2.1).
“The biology of the immune system, as we could measure it from the serum, was different among the women with peripartum cardiomyopathy vs. the women with nonperipartum cardiomyopathy,” Adamo told Healio. “This was remarkable to us, because there is plenty of literature that says inflammation plays a role in HF, but this was not just that. We were seeing something different than inflammation between the women with peripartum cardiomyopathy and women with any type of HF.”
Cardiac recovery by 12 months among women with peripartum cardiomyopathy was associated with the downregulation of pro-inflammatory pathways and the upregulation of liver-X receptor/retinoid-X receptor and an additional retinoid-X receptor-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor alpha/retinoid-X receptor alpha signaling, according to the researchers.
“Our study provides the strongest evidence to date that inflammation plays an important role in this disease,” Adamo said.
Data suggest therapeutic targets
Adamo said pharmacological activation of retinoid-X receptor-related signaling could be a potential therapeutic strategy for attenuating adverse cardiac remodeling in peripartum cardiomyopathy, noting that several agonists of these pathways have already been developed or are under investigation for other clinical indications.
“This could be a potential new therapeutic target for these women,” Adamo told Healio. “However, we need to balance the excitement with caution. As exciting as this is, validation of these findings is needed. We would like to extend this study with additional immunological analyses to see if the findings are confirmed. If the findings are confirmed, then, hopefully, we can pursue this target as a new therapy for women with peripartum cardiomyopathy.”
For more information:
Luigi Adamo, MD, PhD, can be reached at ladamo2@jhmi.edu; Twitter: @luigiadamomdphd.
Jana P. Lovell, MD, can be reached at jlovell@jhmi.edu; Twitter: @jlovellmd.
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