Advancing the understanding of rare heart conditions

Posted: 16 January 2024 | | No comments yet

A potential link between truncating variants and the development of DCM has been found, and a patient-focused registry about PPCM was made.

PKP2 gene heart cell

Scientists from the Perelman School of Medicine at the University of Pennsylvania have made advancements the understanding of two rare heart conditions: peripartum cardiomyopathy (PPCM), and dilated cardiomyopathy (DCM). This could serve as important guide in future research toward developing therapies for the conditions.

PPCM is a severe cardiac condition, characterised by the weakening of the heart muscle, leading to reduced cardiac function, affecting approximately 1 in 1,000 pregnant or recently pregnant women. Factors that increase the risk of developing PPCM include advanced maternal age, multiple gestations, anaemia, and hypertensive disorders of pregnancy. Typically, treatment involves standard heart failure management strategies, including medications like diuretics, beta-blockers, and ACE inhibitors. In severe cases, advanced therapies such as LVADs or heart transplantation may be considered.

DCM affects one in 100 people and can occur at any age. Unlike PPCM, it is not specifically related to pregnancy. Risk factors for DCM can include a family history of heart disease, certain infections, exposure to toxins, and other underlying heart conditions.


In the recent JCI study, the team in the lab of Dr Zoltan Arany, the Samuel Bellet Professor of Cardiology and professor of Cell and Developmental Biology concentrated on the role of genetic variants in the TTN gene, which encodes for a crucial protein called titin. Titin has an essential role in the assembly and regulation of heart muscle contraction.  Truncating variants (TTNtvs), specific genetic variants, in the TTN gene may contribute to DCM. Dr Arany and his colleagues developed a patient-specific antibody to detect these TTNtvs in human heart tissue, which revealed that TTNtvs are present in hearts affected by DCM. This indicates potential link between these genetic variants and the development of the disease.

It was also revealed that the truncated titin proteins associated with TTNtvs integrate into the heart’s muscle structure. This suggests that these genetic variants may impact the sarcomere, the basic unit of heart muscle, influencing its structure and function.

Further research

The recent article in the NEJM consolidates current knowledge about PPCM, but also provides a roadmap for navigating the complexities of the disease. Previous research from the Arany lab has highlighted the racial disparities in PPCM, with black women in the US being four times more likely than white women to develop the disease.

PPCM is now a leading cause of maternal mortality in many parts of the globe, so the article emphasises the dire need for early diagnosis and the development of effective management strategies. Dr Arany explained: “There is a great need for further research into long-term outcomes, racial disparities, and the underlying mechanisms of PPCM…We hope our recent research signals a call to action for the medical community to address this critical issue affecting young women, their families, and newborns.”

There is a profound lack of research in PPCM. Therefore, to make important discoveries, doctors at the Perelman School of Medicine created PPCM-R, the first patient-focused registry about PPCM. A database of PPCM survivor medical records driven by patients will be generated in attempt to answer important research questions and prevent the disease.

This study was published in the New England Journal of Medicine (NEJM), adding to separate research the team recently published in the Journal of Clinical Investigation (JCI).

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