A mother’s heart: How pregnancy shapes women's heart health

Cardiovascular disease, the leading cause of death in women worldwide, is responsible for 40 per cent of female mortality annually [1]. Yet, its impact during pregnancy – a time of profound physiological changes – remains an underexplored field in medical research.

During pregnancy, the cardiovascular system undergoes dramatic adaptations to support the growing foetus. Blood flow, heart rate, and cardiac output all increase significantly, presenting unique challenges to the heart.

When these changes proceed smoothly, they represent a remarkable example of the body’s resilience. However, if the heart cannot keep pace or there is a marked increase in blood pressure, conditions such as peripartum cardiomyopathy and preeclampsia can arise, endangering both maternal and foetal health [2].

Shockingly, treatments for heart failure, including these pregnancy-related conditions, are often based on studies involving male subjects, leaving women underserved in diagnosis and care. 

Our research aims to address this critical gap by examining how pregnancy reshapes the female heart at the cellular level, paving the way for more effective, personalised treatments [3, 4].

The unique challenges of pregnancy

During pregnancy, a woman’s heart must pump 30-50 per cent more blood to sustain both her own body and that of her developing baby as well as the placenta. While most hearts adapt to this increased workload, some fail to adjust adequately, resulting in severe complications [5].

Peripartum cardiomyopathy, for instance, weakens and enlarges the heart muscle, reducing its ability to pump blood effectively [6]. Preeclampsia, characterised by high blood pressure and organ dysfunction (Svangerskapet er en stresstest for senere hjerte- og karsykdom), is strongly associated with long-term cardiovascular risks. Regrettably, these conditions often remain undiagnosed today until serious symptoms manifest, leaving women vulnerable.

A review of medical records (2007-2020) in Norway (Medical Birth Registry of Norway) uncovered more than 700 pregnancies complicated by heart failure and cardiomyopathy, emphasising the need for focused research into the cardiovascular risks of pregnancy. 

Understanding these complications could save lives by identifying at-risk individuals early and implementing preventive strategies.

Investigating the heart’s cellular response

At the core of our work at the Institute for Experimental Medical Research, is uncovering how cardiomyocytes – the muscle cells responsible for heart contractions – adapt during pregnancy. These cells rely on tiny structures called cardiac dyads, which translate the electrical signals into the calcium release that is necessary to trigger an efficient heartbeat [7, 8].

Disruptions in dyad function are a hallmark of heart failure. Yet, little is known about how these structures behave in the female heart, particularly during pregnancy. Using advanced imaging techniques like super resolution microscopy, we are exploring these differences in unprecedented detail.

By studying large mammalian models with cardiac physiology similar to humans, we aim to understand the structural and functional changes that occur in the heart during healthy pregnancies and how these changes may become adverse during peripartum cardiomyopathy or preeclampsia. 

We expect that these findings will uncover biomarkers for early detection of these conditions, and novel therapeutic strategies.

Towards targeted treatment for women's cardiovascular health

Understanding how the female heart responds to pregnancy is vital for developing effective, personalised treatments. The historical underrepresentation of women in cardiovascular research has left critical gaps in care, particularly for pregnant women. 

Addressing these disparities is not just a matter of scientific curiosity – it is an urgent public health priority.

By investigating the molecular mechanisms underlying pregnancy-related heart disease, we aim to ensure that women receive care tailored to their unique biological characteristics, improving outcomes and advancing equity in healthcare.

References:

1. Vogel, B., et al., The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet, 2021. 397(10292): p. 2385-2438.
2. Bright, R.A., et al., Maternal Heart Failure. J Am Heart Assoc, 2021. 10(14): p. e021019.
3. Whitelaw, S., et al., Trial characteristics associated with under-enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review. Eur J Heart Fail, 2021. 23(1): p. 15-24.
4. Romiti, G.F., et al., Sex and Gender-Related Issues in Heart Failure. Cardiol Clin, 2022. 40(2): p. 259-268.
5. Hall, M.E., E.M. George, and J.P. Granger, [The heart during pregnancy]. Rev Esp Cardiol, 2011. 64(11): p. 1045-50.
6. Ricke-Hoch, M., T.J. Pfeffer, and D. Hilfiker-Kleiner, Peripartum cardiomyopathy: basic mechanisms and hope for new therapies. Cardiovasc Res, 2020. 116(3): p. 520-531.
7. Setterberg, I.E., et al., The Physiology and Pathophysiology of T-Tubules in the Heart. Front Physiol, 2021. 12: p. 718404.
8. Manfra, O., M. Frisk, and W.E. Louch, Regulation of Cardiomyocyte T-Tubular Structure: Opportunities for Therapy. Curr Heart Fail Rep, 2017. 14(3): p. 167-178.

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